Wiki Books

Here you can access all Wiki Books on the medic debate site. If you want to start a new collaborative scientific Wiki book, just click on "Add Child Page" below. Please check that there are no Wiki books published before on the same subject. If there is, we instead recommend you to improve and update the already published wiki book. When filling in the form, all the items,like appropriate category listings etc do not need to be completely filled in if you are insecure about what to do. The adminitrators will fix it later even if it is not perfect directly.

Cancer Treatments

field_vote: 

In this section we intend to give information about all kinds of cancer treatments that are not yet wholeheartedly part of the conventinal allopathic medicine.

Anti-Cancer Infusions

field_vote: 

Here is a list of all kind of anti cancer infusion therapies:

Disease(s): 

IV Artesunate

field_vote: 

Artesunate has been used worldwide for many years and is recommended by the World Health Organization for the treatment of severe malaria. However, data indicates IV Vitamin C (IVC) in conjunction with IV Artesunate makes a substantial difference in advanced cancers.

IV Artesunate often is administered right before high dose IV Vitamin C and there is evidence that these therapies work synergistically together. In patients with Stage IV breast cancer, after one year the group that received no IVC and IV Artesunate had a 74 percent survival rate — compared to the IVC and IV Artesunate group which had a 90 percent survival rate after one year.

By year 2 the results were even more significant: The group that did not receive treatment had a 68 percent survival rate compared to 90 percent in the treatment group. [1]

It is also important to note that no adverse events were associated with this treatment.

Clinics that offer
IV Artesunate

Cancer Tutor Verified

 
 
 

Artesunate administered with IVC provides significant advantages for improved survival, improved tumor sensitivity to chemotherapy, reduced side effects of chemo, and improved energy, appetite, and quality of life.

Artesunate also has been analyzed for its anti-cancer activity against 55 cell lines of the Developmental Therapeutics Program of the National Cancer Institute.

Artesunate was most active against leukemia and colon cancer cell lines. Non-small cell lung cancer cell lines showed the highest mean GI50 value, indicating the lowest sensitivity toward artesunate in this test panel. Intermediate GI50 values also were obtained for melanomas, breast, ovarian, prostate, CNS, and renal cancer cell lines. [2]

Artemisinin and its derivatives dihydroartemisinin and artesunate were researched in 2010 for its anti-cancer activity. In a panel of chemosensitive and chemoresistant human neuroblastoma cells as well as in primary neuroblastoma cultures, artesunate was proven more active in affecting neuroblastoma cell viability.

Artesunate also has been shown to induce oncosis-like cell death in vitro and has anti-tumor activity against pancreatic cancer xenografts in vivo. [4]

In 2015, results were published from a double-blind pilot study of oral artesunate therapy for colorectal cancer. It concluded larger clinical studies with artesunate should be implemented and may provide an intervention where none is currently available, as well as synergistic benefits with current regimens. [5]

Article Information
  1. Dr. Adam McLeod. Yaletown Naturopathic Clinic. How does Artesunate kill cancer?
  2. The anti-malarial artesunate is also active against cancer. Efferth T, Dunstan H, Sauerbrey A, Miyachi H, Chitambar CR. Int J Oncol. 2001 Apr;18(4):767-73. PMID: 11251172
  3. Anti-cancer effects of artesunate in a panel of chemoresistant neuroblastoma cell lines. Michaelis M, Kleinschmidt MC, Barth S, Rothweiler F, Geiler J, Breitling R, Mayer B, Deubzer H, Witt O, Kreuter J, Doerr HW, Cinatl J, Cinatl J Jr. Biochem Pharmacol. 2010 Jan 15;79(2):130-6. doi: 10.1016/j.bcp.2009.08.013. PMID: 19698702
Therapeutic Substance(s): 
Therapeutic intervention: 
Disease(s): 

Bio-Immune therapy according to Professor Thomas Tallberg, a cure for Melanoma?

field_vote: 

 

Already in the early 1940s, it was discovered that leukemias and sarcomas in rats can be healed and prevented by adding certain amino acids and trace elements to their diets.

Prof Thomas Tallberg from Helsiniki continued to develop these research findings into therapeutic modalities available for treatment of human cancers. He also found that when cancer cells receive these amino acids and minerals, their respiratory organs, or mitochondria, change shape and become dense with electrons. The next thing that happens is that the cancer cells transform into normal cells. This means that he has found a method which can correct the metabolic aberration in certain cancer cells, so that they can stop being cancer cells and continue their natural differentiation into normal cells. In many cases, he has thus managed to heal skin tumors in both animals and humans without even leaving a scar!!
He has published controlled clinical studies showing how, among other things, he completely healed 60% of stage 4 malignant melanomas, 90-100% of melanomas of the eye (uveal mealanomas) and 30% of stage 4 kidney cancers, conditions that are normally almost 100% lethal.
He has so far found the formulae for treating malignant melanomas, breast, prostate, kidney and gastrointestinal cancers with great success. He can also treat psoriasis with this method with an almost 100% success rate.















Besides taking one or two scoops of amino-acid/mineral powder each day, Dr Tallberg also recommends  a small amount (50 g) of mammalian brain each day.  According to Tallberg, this has the dual effect of boosting the immune system and providing a balanced intake of essential lipids. He himself sells cans of piglet brain pate, that can be used as spread on bread, mixed with ice cream or served as a dessert resembling pina colada.
He also uses a special kind of autologous vaccine, made from the patient's own tumor tissue, and recommends avoidance of certain types of food nutrients for different types of cancer that can stimulate cancer growth, ie molybdenum for breast cancer patients and zinc for kidney cancer patients.
We can provide the Tallberg protein/mineral powders and mammalian brain and we have plans to create a labaratory for making the autologous cancer vaccines.
Currently, these vaccines cannot be made anywhere on planet earth except in Tallberg’s own labaratory, and as he is presently 77 years old, he is trying to reduce his workload, and therefore does not accept new patients.

 

Therapeutic intervention: 

Cancer Psychotherapy according to Dr. Frederick B Levenson

field_vote: 

Dr Frederick B Levenson started his work doing psychotherapy with cancer patients 1974, when he started working with psychotherapy with a stage IV breast cancer patient, with the primary goal of aiding their capacity to regulate and discharge irritation.

To his astonishment, he discovered that the patient started to get better from her cancer, as she more and more connected to Dr. Levenson in the psychotherapeutic process, and in the end, she was totally free from cancer. He discovered that she was not the only one that could get healed from cancer by using this method, and during the years he refined his techniques, with even better results as a consequence. In a publication from 2010 where the medical records and the records of dr Levenson during a 35 year period were reviewed, one could clearly demonstrate a positive effect on patient longevity and both observed and reported patient quality of life.

In this paper  75 cases treated during 1974 to 2008 were discussed. Almost all patients were diagnosed with "incurable" cancers treated by oncologists at esteemed medical centres. All subjects  within this sample, with the exception of two who died immediately after the initialisation of treatment experienced an improved quality of life according to case records and reviewed documentation- 33 (44%) are still alive, 80% survived for more than five years and 45%survived for more than 10 years. A noticeable trend of improved patient quality of life and longevity had occurred as Levenson refined and improved his treatment methodology over the decades. The patients often sought treatment after a terminal diagnosis and were informed that allopathic biomedical interventions could not alter their prognosis. There seemed to be an improvement in longevity and several spontaneous remissions were noted in the hospital documentation.

The basic principles of the treatment is that cancer is not seen as a disease, but a process, that can be reversed. Everyone has cancer cells in his/hers body all the time, but normally these cells are taken care of by the immune system, so that no serious problems will develop. Cancer cells are embryonic cells that do not complete there maturation process into fully differentiated, adult cells, and Dr Levenson postulates that the reason for this lack of maturation of certain cells lies in early traumas, and lack of adequate emotional support in early childhood as well as later in life.

The typical psychopatological feature for many cancer patients is the so called anaclitic depression, a state characterised by an inability to form constructive, close relationships with a "melting" fusional quality, based on mutual closeness and trust. Cancer patients often have a tendency to take care of everyone else but themselves, forgetting to prioritise their own needs.

In order to heal these, often very early wounds and personality patterns, it is necessary to let the therapist become like a surrogate mother, that "adopts" the patient in order to give support through two 45 minute talks a week plus daily contact over the telephone for a couple of minutes. It is also always possible to call the therapist 24/7 in emergency situations. If you cannot come to the therapist physically, sessions can be performed over a landline telephone or Skype.

With Dr Mikael Nordfors, medical support is also included in the consultations. Dr Levenson cannot take on any new patients at the moment because he is prioritizing educating new therapists.

The cost is 950 Euro/month.

If you are interested, you can contact Dr Mikael Nordfors on telephone +45 31530931 or by e-mail: mnordfors@gmail.com

 

Therapeutic intervention: 

DCA

field_vote: 

From www.wikipedia.org
Dichloroacetic acid, often abbreviated DCA, is a chemical compound, an acid, and an analogue of acetic acid in which two of the three hydrogen atoms of the methyl group have been replaced by chlorine atoms, it has the chemical formula CHCl2COOH. The salts and esters of dichloroacetic acid are called dichloroacetates.
 

Chemistry and occurrence
The chemistry of dichloroacetic acid is typical for halogenated organic acids. It is a member of the chloroacetic acids family. The dichloroacetate ion is produced when dissolved in water. As an acid with a pKa of 1.48,[4]
pure dichloroacetic acid is very corrosive and extremely destructive to
tissues of the mucous membranes and upper respiratory tract.[5]
DCA does not occur in nature. It is a trace product of the chlorination of drinking water and is produced by the metabolism of various chlorine-containing drugs or chemicals.[6] It is typically prepared by the reduction of trichloroacetic acid.
Therapeutic use
Owing to the highly corrosive action of the acid, only the salts of dichloroacetic acid are used therapeutically, including its sodium and potassium salts, sodium dichloroacetate and potassium dichloroacetate.
Lactic acidosis
The dichloroacetate ion stimulates the activity of the enzyme pyruvate dehydrogenase by inhibiting the enzyme pyruvate dehydrogenase kinase.[7] Thus, it decreases lactate production by shifting the metabolism of pyruvate from glycolysis towards oxidation in the mitochondria. This property has led to trials of DCA for the treatment of lactic acidosis in humans.[8][9][10][11]
A randomized controlled trial in children with congenital lactic acidosis found that while DCA was well tolerated, it was ineffective in improving clinical outcomes.[9] A separate trial of DCA in children with MELAS (a syndrome of inadequate mitochondrial function, leading to lactic acidosis) was halted early, as all 15 of the children receiving DCA experienced significant nerve toxicity without any evidence of benefit from the medication.[10]
A randomized controlled trial of DCA in adults with lactic acidosis
found that while DCA lowered blood lactate levels, it had no clinical
benefit and did not improve hemodynamics or survival.[11]
Thus, while early case reports and pre-clinical data suggested that
DCA might be effective for lactic acidosis, subsequent controlled
trials have found no clinical benefit of DCA in this setting. In
addition, clinical trial subjects were incapable of continuing on DCA
as a study medication owing to progressive toxicities.


Potential cancer applications
Cancer cells generally use glycolysis rather than respiration (oxidative phosphorylation) for energy (the Warburg effect), as a result of hypoxia that exists in tumors and damaged mitochondria.[12] Usually dangerously damaged cells kill themselves via apoptosis, a mechanism of self-destruction that involves mitochondria, but this mechanism fails in cancer cells.
A study published in January 2007 by researchers at the University of Alberta,[13] testing DCA on in vitro
cancer cell lines and a rat model, found that DCA restored
mitochondrial function, thus restoring apoptosis, killing cancer cells in vitro, and shrinking the tumors in the rats.[14]
These results received extensive media attention, beginning with an article in New Scientist titled "Cheap, ‘safe’ drug kills most cancers".[15] Subsequently, the American Cancer Society and other medical organizations have received a large volume of public interest and questions regarding DCA.[16] Reports have since pointed out that although the study results are promising, no formal clinical trials
in humans with cancer have yet been conducted in the USA and are not
yet final in Canada, emphasizing the need for caution in interpreting
the preliminary results.[16][17]
Some doctors are treating cancer using DCA "off-label",[18][19] which generates controversy in some circles.[18] The off-label use
of prescription drugs is common practice for cancer patients at the
most prestigious medical institutions in the world, especially those
diagnosed with cancers designated as orphan diseases, for which very few government-approved therapies are available. For example, to treat the grade IV brain cancer called glioblastoma, UCLA Neuro-oncology uses some 50 different drugs, only 4 of which are currently FDA-approved to treat glioblastoma.[20] Oral DCA, which has been safely used to treat lactic acidosis for more than 30 years in humans[14] (but see above), is currently in human clinical trials for glioblastoma.[21]
Drs. Akbar and Humaira Khan have since March 2007 treated cancer
patients using DCA off-label at their private clinic, Medicor Cancer
Centres, in Toronto.[22]
They have treated several types of cancer and said on their web site
that some patients "are showing varied positive responses to DCA
including tumour shrinkage, reduction in tumour markers, symptom
control, and improvement in lab tests".[19]
Although, they have not published their results nor reported it at
medical conferences, they have uploaded details of patient responses
and overall statistics on their web site. [23]
Dr. Terry Polevoy, of Kitchener, Ontario, called on the College of
Physicians and Surgeons of Ontario to take away the Khans' licences for
offering a compound that hasn't been proven to shrink tumours in
humans. "They are not oncologists. They should not be making these
decisions. I think they should be disciplined for using this stuff.
That, to me, is unethical, to use something that has never been proved
to do anything." But the College said that it was not their role to say
which therapies a doctor can use.[24]
Dr. Polevoy himself is not an oncologist, but a medical doctor who runs
an acne clinic in Kitchener, Ontario, as well as a web site devoted to
exposing what he considers self-promotion and self-described "quack
remedies" called Healthwatcher.net[25].
The New Scientist later editorialized, "The drug may yet live
up to its promise as an anti-cancer agent – clinical trials are
expected to start soon. It may even spawn an entirely new class of
anti-cancer drugs. For now, however, it remains experimental, never yet
properly tested in a person with cancer. People who self-administer the
drug are taking a very long shot and, unlikely as it may sound, could
even make their health worse."[26]
DCA has been used historically to treat patients with lactic
acidosis, and therefore could arguably enter phase 2 trials in patients
with cancer.[27]
DCA is non-patentable as a compound, though a patent has been filed for its use in cancer treatment.[28] Research by Dr. Evangelos Michelakis has received no support from the pharmaceutical industry.
Concerns have been raised that without strong intellectual property
protection, the financial incentive for pharmaceutical industry
interest is reduced, and therefore clinical trials of DCA may not be
funded.[15][16][17][29] However, other sources of funding exist; previous studies of DCA have been funded by government organizations such as the National Institutes of Health, the Food and Drug Administration, the Canadian Institutes of Health Research and by private charities (e.g. the Muscular Dystrophy Association).
Recognizing anticipated funding challenges, Dr Michelakis's lab took
the unorthodox step of directly soliciting online donations to fund the
research.[30]
After 6 months, his lab had raised over $800,000, enough to fund a
small Clinical Phase 2 study. Dr. Michelakis and Dr. Archer have
applied for a patent on the use of DCA in the treatment of cancer.[31][32]
On 24 September 2007,
the Department of Medicine of Alberta University reported that after
the trial funding was secured, both the Alberta local ethics committee
and Health Canada approved the first DCA Clinical Trial in Cancer.[33] This initial trial is relatively small (enrollment- up to 50 patients in the following 18 months).
The promise of DCA as a cheap, effective and safe treatment for
cancer generated a great deal of public interest. Many people turned to
self-medication. [34][35]
When faced with the high costs of getting Food and Drug Administration approval, estimated by Tufts University to exceed one billion dollars [36],
the chance of getting DCA approved for the treatment of cancer in the
United States is extremely low. This problem is highlighted in the 2007
New York Times article by Ralph Moss titled "Patents over Patients" [37].
Side effects
Reports in the lay press after the 2007 University of Alberta announcement claim that dichloroacetate "has actually been used safely in humans for decades",[38] but the limited scholarly literature suggests side effects of pain, numbness and gait disturbances in some patients.[38] A clinical trial where DCA was given to patients of MELAS (a form of genetically inherited lactic acidosis) at 25 mg/kg/day was ended prematurely due to excessive peripheral nerve toxicity.[39] Dichloroacetate can also have anxiolytic or sedative effects.[6]
Animal studies suggest that the neuropathy and neurotoxicity during chronic dichloroacetate treatment may be partly due to depletion of thiamine, and thiamine supplementation in rats reduced these effects.[40]
However, more recent studies in humans suggest that peripheral
neuropathy is a common side effect during chronic DCA treatment, even
with coadministration of oral thiamine.[41][42]
An additional study reported that 50 mg/kg/day DCA treatment resulted
in unsteady gait and lethargy in two patients, with symptoms occurring
after one month for one patient and two months for the second. Gait
disturbance and consciousness were recovered with cessation of DCA,
however sensory nerve action potentials did not recover in one month.[43]
Studies of the trichloroethylene (TCE) metabolites dichloroacetic acid (DCA), trichloroacetic acid (TCA), and chloral hydrate suggest that both DCA and TCA are involved in TCE-induced liver tumorigenesis and that many DCA effects are consistent with conditions that increase the risk of liver cancer in humans at dosages much higher than used for cancer therapy.[44]
It has been reported that animals and patients treated with DCA have elevated levels of delta-aminolevulinic acid
(delta-ALA) in the urine. A study published in 2008 suggests that this
product may be the cause of the neurotoxic side-effect of DCA by
blocking peripheral myelin formation. ([1])

Therapeutic Substance(s): 
Therapeutic intervention: 
Disease(s): 

Experimental Radiology

field_vote: 

On this page, we will list all kinds of Experimental Radiological Cancer Therapies, including Radionukleid Therapies.

Therapeutic intervention: 
Disease(s): 

Carbon-ion treatment

field_vote: 

Heavy-ion therapy

From Wikipedia

Heavy-ion therapy is the use of particles more massive than protons or neutrons, such as carbon ions. Compared to protons, carbon ions have an advantage: due to the higher density of ionization at the end of their range,[8] correlated damages of the DNA structure within one cell occur more often so that it becomes more difficult for the cancerous cell to repair the damage. This increases the biological efficiency of the dose by a factor between 1.5 and 3. Compared to protons, carbon ions have the disadvantage that beyond the Bragg peak, the dose does not decrease to zero,[8] since nuclear reactions between the carbon ions and the atoms of the tissue lead to production of lighter ions which have a higher range. Therefore, some damage occurs also beyond the Bragg peak.

By the end of 2008, more than 5,000 patients had been treated using carbon ions.[5]

At the end of 2013, around 13 000 patients had received carbon-ion therapy[7]

Particle beams offer benefits over conventional photon radiation for the treatment of many tumors. Currently, 49 facilities worldwide— including 14 in the US—are producing proton beams, and another 29 are under construction. But carbon-ion therapy, which can benefit patients with deepseated or radiation-resistant tumors, remains in relative infancy, with eight centers operating and four under construction as of 1 April.[citation needed]

Carbon-ion treatment centers in operation

The Particle Therapy Co-Operative Group lists treatment centers in operation or in the planning or construction stage.[5] At least five centers using carbon ions are in operation, four in Japan: the HIMAC[9] at Chiba, the HIBMC[10] at Hyogo, and Gunma University's Heavy Ion Medical Center in Maebashi, and SAGA-HIMAT, Tosu. A fifth in Japan is currently under construction, tentatively named "i-ROCK".[11] In Germany, treatment at the Gesellschaft für Schwerionenforschung (GSI)[12] in Darmstadt, which is primarily a physics laboratory, has been discontinued in 2008, but the new HIT[13] in Heidelberg, which is a dedicated facility, started in November 2009. The HIT facility is using robotic technology with sub millimeter precision to position the patients. Moreover, Heidelberg has developed and took into clinical operation in 2011 the first gantry worldwide for proton and ion beams. The rotating part of this structure has a weight of 600 tons. The CNAO in Pavia, Italy opened in 2011 and will be one of the most advanced centers[clarification needed] for particle therapy with hadrons. CNAO will combine precise dose delivery with highly accurate patient alignment based on stereoscopic X-ray imaging.[14] Sophisticated approaches in image-guided particle therapy (IGPT) augments the radiotherapy machines with imaging capabilities and the latest computer vision technology to increase accuracy of target localization and enable patient alignment accuracies of 0.5 mm and better. In January 2015 the Shanghai Proton and Heavy Ion Centre opened after successfully completing the clinical trials.[15] The Marburg ion treatment facility, MIT (Marburger Ionenstrahl Therapie) treated their first patient in October 2015.[16]

Therapeutic intervention: 
Disease(s): 

Cyberknife

field_vote: 

Cyberknife

From Wikipedia, the free encyclopedia

The CyberKnife is a frameless robotic radiosurgery system used for treating benign tumors, malignant tumors and other medical conditions.[1][2] The system was invented by John R. Adler, a Stanford University professor of neurosurgery and radiation oncology, and Peter and Russell Schonberg of Schonberg Research Corporation. It is made by the Accuray company headquartered in Sunnyvale, California.

The CyberKnife system is a method of delivering radiotherapy, with the intention of targeting treatment more accurately than standard radiotherapy.[3] The two main elements of the CyberKnife are:

  1. the radiation produced from a small linear particle accelerator (linac)
  2. a robotic arm which allows the energy to be directed at any part of the body from any direction
 
The main features of the CyberKnife system, shown on a Fanuc robot

Contents

Main features

Several generations of the CyberKnife system have been developed since its initial inception in 1990. There are two major features of the CyberKnife system that are different from other stereotactic therapy methods.

Robotic mounting

The first is that the radiation source is mounted on a general purpose industrial robot. The original CyberKnife used a Japanese Fanuc robot; however, the more modern systems use a German KUKA KR 240. Mounted on the Robot is a compact X-band linac that produces 6MV X-ray radiation. The linac is capable of delivering approximately 600 cGy of radiation each minute – a new 800 cGy / minute model was announced at ASTRO[4] 2007. The radiation is collimated using fixed tungsten collimators (also referred to as "cones") which produce circular radiation fields. At present the radiation field sizes are: 5, 7.5, 10, 12.5, 15, 20, 25, 30, 35, 40, 50 and 60 mm. ASTRO 2007 also saw the launch of the IRIS[4] variable-aperture collimator which uses two offset banks of six prismatic tungsten segments to form a blurred regular dodecagon field of variable size which eliminates the need for changing the fixed collimators. Mounting the radiation source on the robot allows near-complete freedom to position the source within a space about the patient. The robotic mounting allows very fast repositioning of the source, which enables the system to deliver radiation from many different directions without the need to move both the patient and source as required by current gantry configurations.

Image guidance

The second is that the CyberKnife system uses an image guidance system. X-ray imaging cameras are located on supports around the patient allowing instantaneous X-ray images to be obtained.

6D skull

The original (and still utilized) method is called 6D or skull based tracking. The X-ray camera images are compared to a library of computer generated images of the patient anatomy. Digitally Reconstructed Radiographs (or DRR's) and a computer algorithm determines what motion corrections have to be given to the robot because of patient movement. This imaging system allows the CyberKnife to deliver radiation with an accuracy of 0.5mm without using mechanical clamps attached to the patient's skull.[5] The use of the image-guided technique is referred to as frameless stereotactic radiosurgery. This method is referred to as 6D because corrections are made for the 3 translational motions (X,Y and Z) and three rotational motions. It should be noted that it is necessary to use some anatomical or artificial feature to orient the robot to deliver X-ray radiation, since the tumor is never sufficiently well defined (if visible at all) on the X-ray camera images.

 
6D skull tracking

Xsight

Additional image guidance methods are available for spinal tumors and for tumors located in the lung. For a tumor located in the spine, a variant of the image guidance called Xsight-Spine[6] is used. The major difference here is that instead of taking images of the skull, images of the spinal processes are used. Whereas the skull is effectively rigid and non-deforming, the spinal vertebrae can move relative to each other, this means that image warping algorithms must be used to correct for the distortion of the X-ray camera images.

A recent enhancement to Xsight is Xsight-Lung[7] which allows tracking of some lung tumors without the need to implant fiducial markers.[8]

Fiducial

For soft tissue tumors, a method known as fiducial tracking can be utilized.[9] Small metal markers (fiducials) made out of gold for bio-compatibility and high density to give good contrast on X-ray images are surgically implanted in the patient. This is carried out by an interventional radiologist, or neurosurgeon. The placement of the fiducials is a critical step if the fiducial tracking is to be used. If the fiducials are too far from the location of the tumor, or are not sufficiently spread out from each other it will not be possible to accurately deliver the radiation. Once these markers have been placed, they are located on a CT scan and the image guidance system is programmed with their position. When X-ray camera images are taken, the location of the tumor relative to the fiducials is determined, and the radiation can be delivered to any part of the body. Thus the fiducial tracking does not require any bony anatomy to position the radiation. Fiducials are known however to migrate and this can limit the accuracy of the treatment if sufficient time is not allowed between implantation and treatment for the fiducials to stabilize.[10][11]

Synchrony

 
CyberKnife Machine

Another technology of image guidance that the CyberKnife system can use is called the Synchrony system or Synchrony method. This method uses a combination of surgically placed internal fiducials (typically small gold markers, well visible in x-ray imaging), and light emitting optical fibers (LED markers) mounted on the patient skin. LED markers are tracked by an infrared tracking camera. Since the tumor is moving continuously, to continuously image its location using X-ray cameras would require prohibitive amounts of radiation to be delivered to the patient's skin. The Synchrony system overcomes this by periodically taking images of the internal fiducials, and computing a correlation model between the motion of the external LED markers and the internal fiducials. Time stamps from the two sensors (x-ray and infrared LED) are needed to synchronize the two data streams, hence the name Synchrony.

Motion prediction is used to overcome the motion latency of the robot and the latency of image acquisition. Before treatment, a computer algorithm creates a correlation model that represents how the internal fiducial markers are moving compared to the external markers. During treatment, the system continuously infers the motion of the internal fiducials, and therefore the tumor, based on the motion of the skin markers. The correlation model is updated at fixed time steps during treatment. Thus, the Synchrony tracking method makes no assumptions about the regularity or reproducibility of the patient breathing pattern.

To function properly, the system requires that for any given correlation model there is a functional relationship between the markers and the internal fiducials. The external marker placement is also important, and the markers are usually placed on the patient abdomen so that their motion will reflect the internal motion of the diaphragm and the lungs. This method was invented in 1998.[12][13] The first patients were treated at Cleveland Clinic in 2002. Synchrony is utilized primarily for tumors that are in motion while being treated, such as lung tumors and pancreatic tumors.[14][15]

RoboCouch

A robotic six degree of freedom patient treatment couch called RoboCouch[16] improves patient positioning options for treatment.

Frameless

The frameless nature of the CyberKnife also increases the clinical efficiency. In conventional frame-based radiosurgery, the accuracy of treatment delivery is determined solely by connecting a rigid frame to the patient which is anchored to the patient’s skull with invasive aluminum or titanium screws. The CyberKnife is the only radiosurgery device that does not require such a frame for precise targeting.[17] Once the frame is connected, the relative position of the patient anatomy must be determined by making a CT or MRI scan. After the CT or MRI scan has been made, a radiation oncologist must plan the delivery of the radiation using a dedicated computer program, after which the treatment can be delivered, and the frame removed. The use of the frame therefore requires a linear sequence of events that must be carried out sequentially before another patient can be treated. Staged CyberKnife radiosurgery is of particular benefit to patients who have previously received large doses of conventional radiation therapy and patients with gliomas located near critical areas of the brain. Unlike whole brain radiotherapy, which must be administered daily over several weeks, radiosurgery treatment can usually be completed in 1–5 treatment sessions. Radiosurgery can be used alone to treat brain metastases, or in conjunction with surgery or whole brain radiotherapy, depending on the specific clinical circumstances.[18]

By comparison, using a frameless system, a CT scan can be carried out on any day prior to treatment that is convenient. The treatment planning can also be carried out at any time prior to treatment. During the treatment the patient need only be positioned on a treatment table and the predetermined plan delivered. This allows the clinical staff to plan many patients at the same time, devoting as much time as is necessary for complicated cases without slowing down the treatment delivery. While a patient is being treated, another clinician can be considering treatment options and plans, and another can be conducting CT scans.

In addition, very young patients (pediatric cases) or patients with fragile heads because of prior brain surgery cannot be treated using a frame based system. Also, by being frameless the CyberKnife can efficiently re-treat the same patient without repeating the preparation steps that a frame-based system would require.

The delivery of a radiation treatment over several days or even weeks (referred to as fractionation) can also be beneficial from a therapeutic point of view. Tumor cells typically have poor repair mechanisms compared to healthy tissue, so by dividing the radiation dose into fractions the healthy tissue has time to repair itself between treatments.[19] This can allow a larger dose to be delivered to the tumor compared to a single treatment.[20]

Clinical uses

Since August 2001, the CyberKnife system has FDA clearance for treatment of tumors in any location of the body.[21] Some of the tumors treated include: pancreas,[15][22] liver,[23] prostate,[24][25] spinal lesions,[26] head and neck cancers,[27] and benign tumors.[28]

None of these studies have shown any general survival benefit over conventional treatment methods. By increasing the accuracy with which treatment is delivered there is a potential for dose escalation, and potentially a subsequent increase in effectiveness, particularly in local control rates. However the studies cited are so far limited in scope, and more extensive research will need to be completed in order to show any effects on survival.[22]

In 2008 actor Patrick Swayze was among the people to be treated with CyberKnife radiosurgery.[29]

Locations

CyberKnife systems have been installed in over 150 locations,[30] including 100 hospitals in the United States.[31]

Recently – April 2014 – CyberKnife has been installed at Sir Charles Gairdner Hospital, Perth, Australia.[32]

Stanford University has treated over 2,500 patients using the Cyberknife system, and worldwide over 40,000 patients have been treated.[33]

See also

References

 

Therapeutic intervention: 
Disease(s): 

PSMA - Lutetium Treatment

field_vote: 

Lutetium-177 linked to PSMA: an update

 
 
 
 
 
 
5 Votes

 

One of the more important emerging forms of radiotherapy for metastatic castrate-resistant prostate cancer (mCRPC) is the radioactive element lutetium-177 (177Lu) chemically bonded to a ligand — an antibody or a small molecule that attaches to the prostate-specific membrane antigen (PSMA). We’ll call this class of medications [177Lu]PSMA.

PSMA is expressed on the surface of 95 percent of all metastatic prostate cancer cells; see this link for a fuller explanation. Many of the studies on [177Lu]PSMA have been conducted in Germany. Recently, we reported on a small study from Bad Berka, Germany, with some early encouraging results. There have been a few more trial reports since then.

All of the more recently published studies used a ligand called PSMA-617, a small molecule that attaches to PSMA, rather than a PSMA antibody. It was hoped that this ligand would be more specific to prostate cancer cells, with less affinity for salivary glands and kidneys where it can cause side effects and false positives.

Kratchowil et al. at the University of Heidelberg reported on 30 patients treated with one to three cycles of [177Lu]PSMA-617.

  • PSA decreased in 21/30 patients (70 percent).
    • PSA decreased by > 50 percent in 13/30 patients (43 percent)
    • 8/11 patients (73 percent) who had three cycles of therapy had PSA declines >50 percent that were sustained for over 24 weeks; the number and size of their metastases decreased as well.
  • Hematotoxicity (from bone marrow suppression) was mild.
  • Xerostomia (dry mouth), nausea and fatigue were transient and occurred in < 10 percent.
  • Excess radioactivity was cleared from the kidneys within 48 hours.

Rahbar et al. at the University Hospital Münster (again in Germany) reported on 74 patients treated with a single dose of [177Lu]PSMA-617.

  • PSA decreased in 47/74 patients (64 percent).
    • PSA decreased by > 50 percent in 23/74 patients (31 percent)
  • PSA was stable (−50 percent to +25 percent) in 35/74 patients (47 percent)
  • PSA increased by > 25 percent in 17/74 patients (23 percent)
  • No significant loss of red blood cells, white blood cells, or kidney function
  • Mild decline in platelets, but within normal range

Rahbar et al. also report outcomes on 28 patients after one vs. two treatments.

  • PSA decreased in 59 percent of patients after one treatment and in 75 percent after two treatments.
    • PSA decreased by > 50 percent in 32 percent of patients after one treatment and in 50 percent after two treatments.
  • Median survival was 29 weeks, compared to 20 weeks based on historical expectations.
  • No clinically significant or lasting toxicity occurred.

Radiotherapy with 177Lu, though encouraging, is still in its early days. There is much work to be done in identifying the optimal ligand, optimal dose, optimal number of treatments, optimal patient/disease characteristics, and adjuvant therapies. We encourage participation in clinical trials in the US (see NCT00859781) and in Germany.

Editorial note: This commentary was written for The “New” Prostate Cancer InfoLink by Allen Edel.

Therapeutic Substance(s): 
Therapeutic intervention: 

Proton Therapy

field_vote: 

Proton therapy

From Wikipedia, the free encyclopedia
 
Proton therapy equipment at the Mayo Clinic in Rochester, Minnesota

Proton therapy, or proton beam therapy, is a medical procedure, a type of particle therapy that uses a beam of protons to irradiate diseased tissue, most often in the treatment of cancer. The chief advantage of proton therapy over other types of external beam radiotherapy is that as a charged particle the dose is deposited over a narrow range and there is minimal exit dose.

Contents

Description

 
In a typical treatment plan for proton therapy, the spread out Bragg peak (SOBP, dashed blue line) is the therapeutic radiation distribution. The SOBP is the sum of several individual Bragg peaks (thin blue lines) at staggered depths. The depth-dose plot of an X-ray beam (red line) is provided for comparison. The pink area represents additional doses of X-ray radiotherapy—which can damage normal tissues and cause secondary cancers, especially of the skin.[1]

Proton therapy is a type of external beam radiotherapy that uses ionizing radiation. In proton therapy, medical personnel use a particle accelerator to target a tumor with a beam of protons.[2][3] These charged particles damage the DNA of cells, ultimately killing them or stopping their reproduction. Cancerous cells are particularly vulnerable to attacks on DNA because of their high rate of division and their reduced abilities to repair DNA damage.

Because of their relatively large mass, protons have little lateral side scatter in the tissue; the beam does not broaden much, stays focused on the tumor shape and delivers only low-dose side effects to surrounding tissue. All protons of a given energy have a certain range; very few protons penetrate beyond that distance.[4] Furthermore, the dose delivered to tissue is maximized only over the last few millimeters of the particle’s range; this maximum is called the Bragg peak, often referred to as the SOBP.[5]

To treat tumors at greater depths, the proton accelerator must produce a beam with higher energy, typically given in eV or electron volts. Proton therapy treats tumors closer to the surface of the body with lower energy protons. Accelerators used for proton therapy typically produce protons with energies in the range of 70 to 250 MeV. Adjusting proton energy during the treatment maximizes the cell damage the proton beam causes within the tumor. Tissue closer to the surface of the body than the tumor receives reduced radiation, and therefore reduced damage. Tissues deeper in the body receive very few protons, so the dosage becomes immeasurably small.[4]

In most treatments, protons of different energies with Bragg peaks at different depths are applied to treat the entire tumor. These Bragg peaks are shown as thin blue lines in the figure to the right. The total radiation dosage of the protons is called the spread-out Bragg peak (SOBP), shown as a heavy dashed blue line in figure to the right. It is important to understand that, while tissues behind or deeper than the tumor receive almost no radiation from proton therapy, the tissues in front of or shallower than the tumor receive radiation dosage based on the SOBP.

History

The first suggestion that energetic protons could be an effective treatment method was made by Robert R. Wilson[6] in a paper published in 1946 while he was involved in the design of the Harvard Cyclotron Laboratory (HCL).[7] The first treatments were performed with particle accelerators built for physics research, notably Berkeley Radiation Laboratory in 1954 and at Uppsala in Sweden in 1957. In 1961, a collaboration began between HCL and the Massachusetts General Hospital (MGH) to pursue proton therapy. Over the next 41 years, this program refined and expanded these techniques while treating 9,116 patients[8] before the cyclotron was shut down in 2002. The world's first hospital-based proton therapy center was a low energy cyclotron centre for ocular tumours at the Clatterbridge Centre for Oncology in the UK, opened in 1989,[9] followed in 1990 at the Loma Linda University Medical Center (LLUMC) in Loma Linda, California. Later, The Northeast Proton Therapy Center at Massachusetts General Hospital was brought online, and the HCL treatment program was transferred to it during 2001 and 2002. By 2010 these facilities were joined by an additional seven regional hospital-based proton therapy centers in the United States alone, and many more worldwide.[10]

Application

Physicians use protons to treat conditions in two broad categories:

  • Disease sites that respond well to higher doses of radiation, i.e., dose escalation. In some instances, dose escalation has demonstrated a higher probability of "cure" (i.e., local control) than conventional radiotherapy.[11] These include, among others, uveal melanoma (ocular tumors), skull base and paraspinal tumors (chondrosarcoma and chordoma), and unresectable sarcomas. In all these cases proton therapy achieves significant improvements in the probability of local control over conventional radiotherapy.[12][13][14] In treatment of ocular tumors, proton therapy also has high rates of maintaining the natural eye.[15]

The second broad class are those treatments where proton therapy's increased precision reduces unwanted side effects by lessening the dose to normal tissue. In these cases, the tumor dose is the same as in conventional therapy, so there is no expectation of an increased probability of curing the disease. Instead, the emphasis is on reducing the integral dose to normal tissue, thus reducing unwanted effects.[11]

Two prominent examples are pediatric neoplasms (such as medulloblastoma) and prostate cancer. In the case of pediatric treatments, a 2004 review gave theoretical advantages but did not report any clinical benefits.[16][17]

In prostate cancer cases, the issue is less clear. Some published studies found a reduction in long term rectal and genito-urinary damage when treating with protons rather than photons (meaning X-ray or gamma ray therapy). Others showed a small difference, limited to cases where the prostate is particularly close to certain anatomical structures.[18][19] The relatively small improvement found may be the result of inconsistent patient set-up and internal organ movement during treatment, which offsets most of the advantage of increased precision.[19][20][20][21] One source suggests that dose errors around 20% can result from motion errors of just 2.5 mm,[citation needed] and another that prostate motion is between 5–10 mm.[22]

However, the number of cases of prostate cancer diagnosed each year far exceeds those of the other diseases referred to above, and this has led some, but not all, facilities to devote a majority of their treatment slots to prostate treatments. For example, two hospital facilities devote roughly 65%[23] and 50%[24] of their proton treatment capacity to prostate cancer, while a third devotes only 7.1%.[25]

Overall worldwide numbers are hard to compile, but one example in the literature shows that in 2003 roughly 26% of proton therapy treatments worldwide were for prostate cancer.[26] Proton therapy for ocular (eye) tumors is a special case since this treatment requires only comparatively low energy protons (about 70 MeV). Owing to this low energy requirement, some particle therapy centers only treat ocular tumors.[8] Proton, or more generally, hadron therapy of tissue close to the eye affords sophisticated methods to assess the alignment of the eye that can vary significantly from other patient position verification approaches in image guided particle therapy.[27] Position verification and correction must ensure that the radiation spares sensitive tissue like the optic nerve to preserve the patient’s vision.

Comparison with other treatments

The issue of when, whether, and how best to apply this technology is controversial.[28][29][30] As of 2012 there have been no controlled trials to demonstrate that proton therapy yields improved survival or other clinical outcomes (including impotence in prostate cancer) compared to other types of radiation therapy, although a five-year study of prostate cancer is underway at Massachusetts General Hospital.[31][32][33][34][34] Proton therapy is far more expensive than conventional therapy.[29][35] As of 2012 proton therapy required a very large capital investment (from US$100M to more than $180M).[28][30][36]

Preliminary results from a 2009 study, including high-dose treatments, showed very few side effects.[37]

NHS Choices has stated:

We cannot say with any conviction that proton beam therapy is “better” overall than radiotherapy. (...) Some overseas clinics providing proton beam therapy heavily market their services to parents who are understandably desperate to get treatment for their children. Proton beam therapy can be very costly and it is not clear whether all children treated privately abroad are treated appropriately.[38][39]

X-ray radiotherapy

 
Irradiation of nasopharyngeal carcinoma by photon (X-ray) therapy (left) and proton therapy (right)

The figure at the right of the page shows how beams of X-rays (IMRT; left frame) and beams of protons (right frame), of different energies, penetrate human tissue. A tumor with a sizable thickness is covered by the IMRT spread out Bragg peak (SOBP) shown as the red lined distribution in the figure. The SOBP is an overlap of several pristine Bragg peaks (blue lines) at staggered depths.

Megavoltage X-ray therapy has less "skin scarring potential" than proton therapy: X-ray radiation at the skin, and at very small depths, is lower than for proton therapy. One study estimates that passively scattered proton fields have a slightly higher entrance dose at the skin (~75%) compared to therapeutic megavoltage (MeV) photon beams (~60%).[1] X-ray radiation dose falls off gradually, unnecessarily damaging tissue deeper in the body and damaging the skin and surface tissue opposite the beam entrance. The differences between the two methods depends on the:

  • Width of the SOBP
  • Depth of the tumor
  • Number of beams that treat the tumor

The X-ray advantage of reduced damage to skin at the entrance is partially counteracted by damage to skin at the exit point.

Since X-ray treatments are usually done with multiple exposures from opposite sides, each section of skin is exposed to both entering and exiting X-rays. In proton therapy, skin exposure at the entrance point is higher, but tissues on the opposite side of the body to the tumor receive no radiation. Thus, X-ray therapy causes slightly less damage to the skin and surface tissues, and proton therapy causes less damage to deeper tissues in front of and beyond the target.[3]

An important consideration in comparing these treatments is whether the equipment delivers protons via the scattering method (historically, the most common) or a spot scanning method. Spot scanning can adjust the width of the SOBP on a spot-by-spot basis, which reduces the volume of normal (healthy) tissue inside the high dose region. Also, spot scanning allows for intensity modulated proton therapy (IMPT), which determines individual spot intensities using an optimization algorithm that lets the user balance the competing goals of irradiating tumors while sparing normal tissue. Spot scanning availability depends on the machine and the institution. Spot scanning is more commonly known as pencil-beam scanning and is available on IBA, Hitachi, Mevion (known as hyperscan [40] and not US FDA approved as of 2015) and Varian.

Surgery

Physicians base the decision to use surgery or proton therapy (or any radiation therapy) on the tumor type, stage, and location. In some instances, surgery is superior (e.g. cutaneous melanoma), in some instances radiation is superior (e.g., skull base chondrosarcoma), and in some instances they are comparable (e.g., prostate cancer). In some instances, they are used together (e.g., rectal cancer or early stage breast cancer). The benefit of external beam proton radiation lies in the dosimetric difference from external beam X-ray radiation and brachytherapy in cases where the use of radiation therapy is already indicated, rather than as a direct competition with surgery.[11] However, in the case of prostate cancer, the most common indication for proton beam therapy, no clinical study directly comparing proton therapy to surgery, brachytherapy, or other treatments has shown any clinical benefit for proton beam therapy. Indeed, the largest study to date showed that IMRT compared with proton therapy was associated with less gastrointestinal morbidity.[41]

Side effects and risks

Proton therapy is a type of external beam radiotherapy, and shares risks and side effects of other forms of radiation therapy. However the dose outside of the treatment region can be significantly less for deep-tissue tumors than X-ray therapy, because proton therapy takes full advantage of the Bragg peak. Proton therapy has been in use for over 40 years, and is a mature treatment technology. However, as with all medical knowledge, understanding of the interaction of radiation (proton, X-ray, etc.) with tumor and normal tissue is still imperfect.[28]

Costs

Historically, proton therapy has been expensive. Goitein & Jermann's[42] analysis had previously determined the relative cost of proton therapy is approximately 2.4 times that of X-ray therapies. However, newer, more compact proton beam sources can be four to five times cheaper and offer more accurate three-dimensional targeting.[43][44] Thus the cost is expected to reduce as better proton technology becomes more widely available. A similar analysis by Lievens & Van den Bogaert[45] determined that the cost of proton therapy is not unrealistic and should not be the reason for denying patients access to this technology. In some clinical situations, proton beam therapy is clearly superior to the alternatives.[46][47] Another study in 2007 expressed concerns about the effectiveness of proton therapy for treating prostate cancer.[48] Although, with the advent of new developments in proton beam technology, such as improved scanning techniques and more precise dose delivery ('pencil beam scanning'), this situation may change considerably.[49] Amitabh Chandra, a health economist at Harvard University, has been quoted as saying that "Proton-beam therapy is like the death star of American medical technology... It's a metaphor for all the problems we have in American medicine.”[50] However, another study has shown that proton therapy in fact brings cost savings.[51] The advent of second generation, and much less expensive, proton therapy equipment now being installed at various sites may change this picture significantly.[52]

Treatment centers

 
Control panel of the synchrocyclotron at the Orsay proton therapy center, France

As of January 2016, there are over 45 particle therapy facilities worldwide.[53] This represents a total of more than 121 treatment rooms available to patients.[54] More than 96,537 patients had been treated.[55]

One hindrance to universal use of the proton in cancer treatment is the size and cost of the cyclotron or synchrotron equipment necessary. Several industrial teams are working on development of comparatively small accelerator systems to deliver the proton therapy to patients.[56] Among the technologies being investigated are superconducting synchrocyclotrons (also known as FM Cyclotrons), ultra-compact synchrotrons, dielectric wall accelerators,[56] and linear particle accelerators.[44]

United States

Proton treatment centers in the United States as of 2017 (in chronological order of first treatment date) include:[9][57]

InstitutionLocationYear of first treatmentComments
University of California, Davis, Crocker Nuclear Laboratory[58] Davis, CA 1994 Ocular treatments only (low energy accelerator)
Loma Linda University Medical Center[59] Loma Linda, CA 1990 First hospital-based facility in USA It uses the Spread Out Bragg's Peak (SOBP) shown in the above illustration.
Francis H. Burr Proton Center (formerly NPTC) at Massachusetts General Hospital (MGH) Boston, MA 2001 Continuation of Harvard Cyclotron Laboratory/MGH treatment program that began in 1961
SCCA Proton Therapy Center at Seattle Cancer Care Alliance Seattle, WA 2001 Part of Fred Hutchinson Cancer Research Center
Indiana University Health Proton Therapy Center Bloomington, IN 2004 Formerly MPRI (Closed 4December 2014)
University of Florida Health Proton Therapy Institute-Jacksonville[60] Jacksonville, FL 2006 The UF Health Proton Therapy Institute is a part of a non-profit academic medical research facility. It is the first treatment center in the Southeast U.S. to offer proton therapy.
University of Texas MD Anderson Cancer Center[61] Houston, TX 2006  
ProCure Proton Therapy Center of Oklahoma[62] Oklahoma City, OK 2009 First of a number of planned ProCure facilities
CDH Proton Center[63] Warrenville, IL 2010 Second of a number of planned ProCure facilities
Roberts Proton Therapy Center, University of Pennsylvania Health System[64] Philadelphia, PA 2010 The largest proton therapy center in the world, the Roberts Proton Therapy Center, which is a part of Penn's Abramson Cancer Center, is also part of a medical complex that includes the Hospital of the University of Pennsylvania, the Perelman Center for Advanced Medicine, and the Children's Hospital of Philadelphia.
Hampton University Proton Therapy Institute Hampton, VA 2010  
ProCure Proton Therapy Center[65] Somerset, NJ 2012 Third of a number of planned ProCure facilities
Siteman Cancer Center[43] St. Louis, MO 2013 First of the new single suite, ultra-compact, superconducting synchrocyclotron,[66] lower cost facilities to treat a patient using the Mevion Medical system's S250.[67]
Provision Proton Therapy Center[68] Knoxville, TN 2014
Scripps Health Scripps Proton Therapy Center [69] San Diego, CA 2014 (5 suites, all using pencil-beam scanning precision also called IMPT) Manufactured by Varian Medical Systems [70]
Ackerman Cancer Center Jacksonville, FL 2015 Ackerman Cancer Center is the world's first private, physician-owned practice to provide proton therapy, in addition to conventional radiation therapy and on-site diagnostic services.
The Laurie Proton Therapy Center, Robert Wood Johnson University Hospital New Brunswick, NJ 2015 The Laurie Proton Therapy Center is home to the world’s third MEVION S250 Proton Therapy System.
Texas Center for Proton Therapy Dallas Fort Worth, Texas 2015 TCPT is a joint venture between Baylor, McKesson, and Texas Oncology. It has three pencil beam rooms and cone beam CT imaging.
Mayo Clinic Cancer Center Phoenix, Arizona 2016 4 treatment rooms, Mayo Clinic Cancer Center Officially opened its doors in February 2016.
Mayo Clinic Jacobson Building Rochester, MN 2016 4 treatment rooms, [2], officially opened its doors in May 2015.
The Marjorie and Leonard Williams Center for Proton Therapy Orlando, Florida 2016 http://www.ufhealthcancerorlando.com/centers/proton-therapy-center Opened its doors in April 2016.
Collaborative Effort: University of Cincinnati Cancer Institute; Cincinnati Childrens Hospital Medical Center Liberty Township, Ohio 2016 http://uchealth.com/cancer/centers-programs/proton-therapy/

https://www.cincinnatichildrens.org/service/p/proton-therapy

MFG: Varian Medical Systems, Operational As Of Sept 2016

Maryland Proton Treatment Center Baltimore, MD 2016 5 treatment rooms, all using pencil-beam scanning. Maryland Proton Treatment Center is affiliated with the University of Maryland Greenebaum Comprehensive Cancer Center.
The Baptist Health of South Florida Miami Cancer Institute (coming soon) Miami, Florida 2017 https://baptisthealth.net/en/health-services/cancer-services/pages/proton-therapy.aspx

Outside the USA

Protontherapy Centres (partial list)[9]
InstitutionMaximum energy (MeV)Year of first treatmentLocationCountry
TRIUMF[71] 74 1995 Vancouver  Canada
Clatterbridge Cancer Centre NHS Foundation Trust, low-energy for ocular[72] 62 1989 Liverpool  United Kingdom
Heidelberg Ion-Beam Therapy Center (HIT) Heidelberg 230 2009 Heidelberg  Germany
Westdeutsches Protonentherapiezentrum Essen 230 2013 Essen  Germany
Helmholtz-Zentrum Berlin in Cooperation with Charité 72 1998 Berlin  Germany
RPTC Rinecker Proton Therapy Center 250 2009 Munich  Germany
PTC Uniklinikum Dresden 230 2014 Dresden  Germany
Wanjie Proton Therapy Center 230 2004 Zibo  China
Proton Medical Research Center University of Tsukuba 250 2001 Tsukuba  Japan
Research Center for Charged Particle Therapy (NIRS) 350-400 1994 Chiba  Japan
Centre de protonthérapie de l'Institut Curie 235 1991 Orsay  France
Centre Antoine Lacassagne 63 1991 Nice  France
Paul Scherrer Institute 250 1984 Villigen   Switzerland
Instytut Fizyki Jądrowej PAN 60 2011 Kraków  Poland
Centrum Cyklotronowe Bronowice 230 2015 Kraków  Poland
Centro per la protonterapia 230 2014 Trento  Italy
Centro Nazionale di Adroterapia Oncologica 250 2011 Pavia  Italy
Proton Therapy Center, Prague 230 2012 Prague  Czech Republic
Shanghai Proton and Heavy Ion Center 230 2014 Shanghai  China
Proton Therapy Center, Korea National Cancer Center 230 2007 Seoul  Korea
Proton and Radiation Therapy Center, Linkou Chang Gung Memorial Hospital 230 2015 Taipei  Taiwan
A. Tsyb Medical Radiological Research Centre 250 2016 Obninsk  Russia
HPTC - Holland Particle Therapy Centre 230 2017 Delft  Netherlands
GPTC - UMC Groningen Protonen Therapie Centrum 230 2018 Groningen  Netherlands

United Kingdom

In 2013 the British government announced that £250 million had been budgeted to establish two centers for advanced radiotherapy, to open in 2018 at the Christie Hospital NHS Foundation Trust in Manchester and University College London Hospitals NHS Foundation Trust. These would offer high-energy proton therapy, currently unavailable in the UK, as well as other types of advanced radiotherapy, including intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT).[73] In 2014, only low-energy proton therapy was available in the UK, at the Clatterbridge Cancer Centre NHS Foundation Trust in Merseyside. But NHS England has paid to have suitable cases treated abroad, mostly in the US. Such cases have risen from 18 in 2008 to 122 in 2013, 99 of whom were children. The cost to the National Health Service averaged around £100,000 per case.[74]

In January 2015, it was announced the UK would get its first high energy proton beam therapy centre a year earlier than expected.[75] A company named Advanced Oncotherapy signed a deal with Howard de Walden Estate to install a machine in Harley Street, the heart of private medicine in London, to be ready by 2017.[76] The company promises that its use of a linear accelerator allows for facilities one-third smaller and one-fifth the cost of facilities based on existing cyclotron designs. The NHS has been criticised by some doctors for buying "old" equipment.[77]

Proton Partners International is developing three centres in Newport, Wales, Bomarsund, Northumberland, and Reading, Berkshire which are expected to open in 2017.[78]

See also

References

  1. "Construction begins on UK's first proton beam therapy cancer treatment centre". Wales on line. 18 January 2016. Retrieved 24 December 2016.

Further reading

  • Greco C.; Wolden S. (Apr 2007). "Current status of radiotherapy with proton and light ion beams". Cancer. 109 (7): 1227–38. doi:10.1002/cncr.22542. PMID 17326046.
  • "Use of Protons for Radiotherapy", A.M. Koehler, Proc. of the Symposium on Pion and Proton Radiotherapy, Nat. Accelerator Lab., (1971).
  • A.M. Koehler, W.M. Preston, "Protons in Radiation Therapy: comparative Dose Distributions for Protons, Photons and Electrons Radiology 104(1):191–195 (1972).
  • "Bragg Peak Proton Radiosurgery for Arteriovenous Malformation of the Brain" R.N. Kjelberg, presented at First Int. Seminar on the Use of Proton Beams in Radiation Therapy, Moskow (1977).
  • Austin-Seymor, M.J. Munzenrider, et al. "Fractionated Proton Radiation Therapy of Cranial and Intracrainial Tumors" Am. J. of Clinical Oncology 13(4):327–330 (1990).
  • "Proton Radiotherapy", Hartford, Zietman, et al. in Radiotheraputic Management of Carcinoma of the Prostate, A. D'Amico and G.E. Hanks. London,UK, Arnold Publishers: 61–72 (1999).

External links

Therapeutic intervention: 

Radiofrequency ablation

field_vote: 

Radiofrequency ablation

From Wikipedia, the free encyclopedia
Radiofrequency ablation
Intervention
ICD-9-CM 01.32, 04.2, 37.33, 37.34, 60.97
MeSH D017115

Radiofrequency ablation (RFA) is a medical procedure in which part of the electrical conduction system of the heart, tumor or other dysfunctional tissue is ablated using the heat generated from medium frequency alternating current (in the range of 350–500 kHz).[1] RFA is generally conducted in the outpatient setting, using either local anesthetics or conscious sedation anesthesia. When it is delivered via catheter, it is called radiofrequency catheter ablation.

Two important advantages of radio frequency current (over previously used low frequency AC or pulses of DC) are that it does not directly stimulate nerves or heart muscle and therefore can often be used without the need for general anesthetic, and that it is very specific for treating the desired tissue without significant collateral damage.[citation needed]

Documented benefits have led to RFA becoming widely used during the last 15 years.[2][3] RFA procedures are performed under image guidance (such as X-ray screening, CT scan or ultrasound) by an interventional pain specialist (such as an anesthesiologist), interventional radiologist, otolaryngologists, a gastrointestinal or surgical endoscopist, or a cardiac electrophysiologist, a subspecialty of cardiologists.

Contents

Tumors

 
CT scan showing radiofrequency ablation of a liver lesion

RFA may be performed to treat tumors in the lung,[4][5][6] liver,[7] kidney, and bone, as well as other body organs less commonly. Once the diagnosis of tumor is confirmed, a needle-like RFA probe is placed inside the tumor. The radiofrequency waves passing through the probe increase the temperature within tumor tissue and results in destruction of the tumor. RFA can be used with small tumors, whether these arose within the organ (primary tumors) or spread to the organ (metastases). The suitability of RFA for a particular tumor depends on multiple factors.

RFA can usually be administered as an out-patient procedure, though may at times require a brief hospital stay. RFA may be combined with locally delivered chemotherapy to treat hepatocellular carcinoma (primary liver cancer). A method currently in phase III trials uses the low-level heat (hyperthermia) created by the RFA probe to trigger release of concentrated chemotherapeutic drugs from heat-sensitive liposomes in the margins around the ablated tissue as a treatment for Hepatocellular carcinoma (HCC).[8] Radiofrequency ablation is also used in pancreatic cancer and bile duct cancer.[9]

RFA has become increasingly important in the care of benign bone tumors, most notably osteoid osteomas. Since the procedure was first introduced for the treatment of osteoid osteomas in the 1990s,[10] it has been shown in numerous studies to be less invasive and expensive, to result in less bone destruction and to have equivalent safety and efficacy to surgical techniques, with 66 to 95% of patients reporting freedom from symptoms.[11][12][13] While initial success rates with RFA are high, symptom recurrence after RFA treatment has been reported, with some studies demonstrating a recurrence rate similar to that of surgical treatment.[14] RFA is also increasingly used in the palliative treatment of painful metastatic bone disease in patients who are not eligible or do not respond to traditional therapies ( i.e. radiation therapy, chemotherapy, palliative surgery, bisphosphonates or analgesic medications).[15]

Cardiology

 
Schematic view of a pulmonary vein ablation. The catheter reaches (from below) through the inferior vena cava, the right atrium and the left atrium, to the orifice of the left upper pulmonary vein.

Radiofrequency energy is used in heart tissue or normal parts to destroy abnormal electrical pathways that are contributing to a cardiac arrhythmia. It is used in recurrent atrial flutter (Afl), atrial fibrillation (AF), supraventricular tachycardia (SVT), atrial tachycardia, Multifocal Atrial Tachycardia (MAT) and some types of ventricular arrhythmia. The energy-emitting probe (electrode) is at the tip of a catheter which is placed into the heart, usually through a vein. This catheter is called the ablator. The practitioner first "maps" an area of the heart to locate the abnormal electrical activity (electrophysiology study) before the responsible tissue is eliminated. Ablation is now the standard treatment for SVT and typical atrial flutter and the technique can also be used in AF, either to block the atrioventricular node after implantation of a pacemaker or to block conduction within the left atrium, especially around the pulmonary veins. In some conditions, especially forms of intra-nodal re-entry (the most common type of SVT), also called atrioventricular nodal reentrant tachycardia or AVNRT, ablation can also be accomplished by cryoablation (tissue freezing using a coolant which flows through the catheter) which avoids the risk of complete heart block - a potential complication of radiofrequency ablation in this condition. Recurrence rates with cryoablation are higher, though.[16] Microwave ablation, where tissue is ablated by the microwave energy "cooking" the adjacent tissue, and ultrasonic ablation, creating a heating effect by mechanical vibration, or laser ablation have also been developed but are not in widespread use.

In 2004, former British prime minister Tony Blair underwent radiofrequency catheter ablation for recurrent atrial flutter.[17][18]

In AF, the abnormal electrophysiology can also be corrected surgically. This procedure, referred to as the "Cox maze procedure", is mostly performed concomitantly with cardiac surgery.

A new and promising indication for the use of radiofrequency technology has made news in the last few years. Hypertension is a very common condition, with about 1 billion people over the world, nearly 75 million in the US alone. Complications of inadequately controlled hypertension are many and have both individual and global impact. Treatment options include medications, diet, exercise, weight reduction and meditation. Inhibition of the neural impulses that are believed to cause or worsen hypertension has been tried for a few decades. Surgical sympathectomy has helped but not without significant side effects. Therefore, the introduction of non-surgical means of renal denervation with radiofrequency ablation catheter was enthusiastically welcomed. Although, the initial use of radiofrequency-generated heat to ablate nerve endings in the renal arteries to aid in management of 'resistant hypertension' were encouraging, the most recent phase 3 studying looking at catheter-based renal denervation for the treatment of resistant hypertension failed to show any significant reduction in systolic blood pressure.[19]

Aesthetics dermatology

Radiofrequency ablation[20] is a dermatosurgical procedure by using various forms of alternating current. Types of radiofrequency are electrosection, electrocoagulation, electrodessication and fulguration. The use of radiofrequency ablation has obtained importance as it can be used to treat most of the skin lesions with minimal side effects and complications.

Varicose veins

Radiofrequency ablation is a minimally invasive procedure used in the treatment of varicose veins. It is an alternative to the traditional stripping operation. Under ultrasound guidance, a radiofrequency catheter is inserted into the abnormal vein and the vessel treated with radio-energy, resulting in closure of the involved vein. Radiofrequency ablation is used to treat the great saphenous vein, the small saphenous vein, and the perforator veins. The latter are connecting veins that transport blood from the superficial veins to the deep veins. Branch varicose veins are then usually treated with other minimally invasive procedures, such as ambulatory phlebectomy, sclerotherapy, or foam sclerotherapy. Currently, the VNUS ClosureRFS stylet is the only device specifically cleared by FDA for endovenous ablation of perforator veins.[21]

It should be pointed out that the possibility of skin burn during the procedure is very small, because the large volumes (500 cc) of dilute Lidocaine (0.1%) tumescent anesthesia injected along the entire vein prior to the application of radiofrequency provide a heat sink that absorbs the heat created by the device. Early studies have shown a high success rate with low rates of complications.[22]

Obstructive sleep apnea

RFA was first studied in obstructive sleep apnea (OSA) in a pig model.[23] RFA has been recognized as a somnoplasty treatment option in selected situations by the American Academy of Otolaryngology[23] but was not endorsed for general use in the American College of Physicians guidelines.[24]

The clinical application of RFA in obstructive sleep apnea is reviewed in that main article, including controversies and potential advantages in selected medical situations. Unlike other electrosurgical devices,[25] RFA allows very specific treatment targeting of the desired tissue with a precise line of demarcation that avoids collateral damage, which is crucial in the head and neck region due to its high density of major nerves and blood vessels. RFA also does not require high temperatures. However, overheating from misapplication of RFA can cause harmful effects such as coagulation on the surface of the electrode, boiling within tissue that can leave "a gaping hole", tears, or even charring.[26]

Pain management

RFA, or rhizotomy, is sometimes used to treat severe chronic pain in the lower (lumbar) back, where radio frequency waves are used to produce heat on specifically identified nerves surrounding the facet joints on either side of the lumbar spine. By generating heat around the nerve, the nerve gets ablated thus destroying its ability to transmit signals to the brain. The nerves to be ablated are identified through injections of local anesthesia (such as lidocaine) prior to the RFA procedure. If the local anesthesia injections provide temporary pain relief, then RFA is performed on the nerve(s) that responded well to the injections. RFA is a minimally invasive procedure which can usually be done in day-surgery clinics, going home shortly after completion of the procedure. The patient is awake during the procedure, so risks associated with general anesthesia are avoided. An intravenous line may be inserted so that mild sedatives can be administered. The major drawback for this procedure is that nerves regenerate over time, so the pain relief achieved lasts for only a short duration (6–24 months) in most patients.[citation needed]

Barrett's esophagus

Radiofrequency ablation has been shown to be a safe and effective treatment for Barrett's esophagus. The balloon-based radiofrequency procedure was invented by Robert A. Ganz, Roger Stern and Brian Zelickson in 1999 (System and Method for Treating Abnormal Tissue in the Human Esophagus). While the patient is sedated, a catheter is inserted into the esophagus and radiofrequency energy is delivered to the diseased tissue. This outpatient procedure typically lasts from fifteen to thirty minutes. Two months after the procedure, the physician performs an upper endoscopic examination to assess the esophagus for residual Barrett's esophagus. If any Barrett's esophagus is found, the disease can be treated with a focal RFA device. Between 80-90% or greater of patients in numerous clinical trials have shown complete eradication of Barrett's esophagus in approximately two to three treatments with a favorable safety profile. The treatment of Barrett's esophagus by RFA is durable for up to 5 years.[27][28][29][30][31]

Other uses

RFA is also used in radiofrequency lesioning, for vein closure in areas where intrusive surgery is contraindicated by trauma, and in liver resection to control bleeding (hemostasis) and facilitate the transection process.

This process has also been used with success to treat TRAP sequence in multiple gestation pregnancies. This is becoming the leading method of treatment with a higher success rate for saving the 'pump' twin in recent studies than previous methods including laser photocoagulation. Due to the rarity of this complication, its correct diagnosis statistics are not yet reliable.

RFA is being investigated to treat uterine fibroids. A system developed by Halt Medical Inc. uses the heat energy of radio frequency waves to ablate the fibroid tissue. The device obtained FDA approval in 2012.[32][33] The device is inserted via a laparoscopic probe and guided inside the fibroid tissue using an ultrasound probe (see video demonstration [2]).

RFA is also used in the treatment of Morton's neuroma[34] where the outcome appears to be more reliable than alcohol injections.[35]

See also

References

  1. Gurdezi S, White T, Ramesh P (2013). "Alcohol injection for Morton's neuroma: a five-year follow-up". Foot Ankle Int. 34: 1064–7. doi:10.1177/1071100713489555. PMID 23669161.

 

Therapeutic intervention: 

Trans Arterial Chemo Embolization(TACE)

field_vote: 
  1. Transcatheter arterial chemoembolization

    From Wikipedia, the free encyclopedia

    Transcatheter arterial chemoembolization (also called transarterial chemoembolization or TACE) is a minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply. Small embolic particles coated with chemotherapeutic drugs are injected selectively through a catheter into an artery directly supplying the tumor. These particles both block the blood supply and induce cytotoxicity, attacking the tumor in several ways.

    The radiotherapeutic analogue (combining radiotherapy with embolization) is called radioembolization or selective internal radiation therapy (SIRT).

    Contents

    Principles

    TACE derives its beneficial effect by two primary mechanisms.[1] Most tumors within the liver are supplied by the proper hepatic artery, so arterial embolization preferentially interrupts the tumor's blood supply and stalls growth until neovascularization. Secondly, focused administration of chemotherapy allows for delivery of a higher dose to the tissue while simultaneously reducing systemic exposure, which is typically the dose limiting factor. This effect is potentiated by the fact that the chemotherapeutic drug is not washed out from the tumor vascular bed by blood flow after embolization. Effectively, this results in a higher concentration of drug to be in contact with the tumor for a longer period of time.[2]

    Park et al. conceptualized carcinogenesis of HCC as a multistep process involving parenchymal arterialization, sinusoidal capillarization, and development of unpaired arteries (a vital component of tumor angiogenesis). All these events lead to a gradual shift in tumor blood supply from portal to arterial circulation. This concept has been validated using dynamic imaging modalities by various investigators. Sigurdson et al. demonstrated that when an agent was infused via the hepatic artery, intratumoral concentrations were ten times greater compared to when agents were administered through the portal vein. Hence, arterial treatment targets the tumor while normal liver is relatively spared. Embolization induces ischemic necrosis of tumor causing a failure of the transmembrane pump, resulting in a greater absorption of agents by the tumor cells. Tissue concentration of agents within the tumor is greater than 40 times that of the surrounding normal liver.

    Therapeutic applications

    Transcatheter arterial chemoembolization has most widely been applied to hepatocellular carcinoma (HCC) for patients who are not eligible for surgery.[3] TACE has been shown to increase survival in patients with intermediate HCC by BCLC criteria. It has also been used as an alternative to surgery for resectable early stage HCC and in patients with regional recurrence of the tumor after previous resection. TACE may also be used to downstage HCC in patients who exceed the Milan criteria for liver transplantation. Other treated malignancies include neuroendocrine tumors, ocular melanoma, cholangiocarcinoma, and sarcoma. Transcatheter arterial chemoembolization plays a palliative role in patients with metastatic colon carcinoma. There is a possible benefit for liver-dominant metastases from other primary malignancies.

    Procedure

    TACE is an interventional radiology procedure performed in the angiography suite. The procedure involves gaining percutaneous transarterial access by the Seldinger technique to the hepatic artery with an arterial sheath, usually by puncturing the common femoral artery in the right groin and passing a catheter guided by a wire through the abdominal aorta, through the celiac trunk and common hepatic artery, and finally into the branch of the proper hepatic artery supplying the tumor. The interventional radiologist then performs a selective angiogram of the celiac trunk and possibly the superior mesenteric artery to identify the branches of the hepatic artery supplying the tumor(s) and threads smaller, more selective catheters into these branches. This is done to maximize the amount of the chemotherapeutic dose that is directed to the tumor and minimize the amount of the chemotherapeutic agent that could damage the normal liver tissue.

    When a blood vessel supplying tumor has been selected, alternating aliquots of the chemotherapy dose and of embolic particles, or particles containing the chemotherapy agent, are injected through the catheter. The total chemotherapeutic dose may be given in one vessel's distribution, or it may be divided among several vessels supplying the tumors.

    The physician removes the catheter and access sheath, applying pressure to the entry site to prevent bleeding. The patient must lie stationary for several hours after the procedure to allow the punctured artery to heal. The patient will often be kept overnight for observation and will likely be discharged the following day. The procedure is normally followed up with a CT scan several weeks later to check the response of the tumor to the procedure.

    Agents

    Lipiodol – mixed with chemotherapeutic agents (Lipiodol is nonocclusive, combined with Gelfoam, Ivalon, or other particles)

    Drug eluting particles – slow, sustained release of loaded drug locally with embolic effect leading to tumor ischemia

    - Polyvinyl alcohol microspheres - loaded with doxorubicin

    - Superabsorbent polymer microspheres - loaded with doxorubicin

    - Gelatin microspheres – loaded with cisplatin

    EmboCept S – Degradable Starch Microspheres (DSM TACE)

    Adverse effects

    As with any interventional procedure, there is a small risk of hemorrhage and/or damage to blood vessels. Pseudoaneurysm can develop at the site of puncture in the femoral artery. During this procedure contrast media is utilized, to which patients may develop an allergic reaction. Symptomatic hypothyroidism may result from the high retained iodine load of the contrast. Off-target delivery of embolic agents such as reflux into healthy surrounding tissue is a potential side effect that may cause complications such as ulceration of the gut or cholecystitis. Specialized techniques and devices may decrease the risk. TACE induces tumor necrosis in more than 50% of patients; the resulting necrosis releases cytokines and other inflammatory mediators into the bloodstream. A self-limiting postembolization syndrome of pain, fever, and malaise may occur due to hepatocyte and tumor necrosis.[4] Transaminases may elevate 100-fold, and a leukemoid reaction is not uncommon.

    Intrahepatic abscess (treated by percutaneous drainage) and gallbladder ischemia are extremely rare. Rising bilirubin is a warning sign of irreversible hepatic necrosis, generally occurring in the setting of cirrhosis. In an effort to reduce the likelihood of significant hepatic toxicity, chemoembolization should be restricted to a single lobe or major branch of the hepatic artery at one time. The patient may be brought back after 1 month, once toxicities and abnormal chemistries have resolved, to complete the procedure in the opposite lobe. Retreatment of new lesions may be necessary, if patients fulfill the original eligibility criteria.

    History

    In 1972, surgical ligation of the hepatic artery was first used to treat recurrent hepatic tumors followed by infusion of 5-fluorouracil into the portal vein. Due to the liver's dual blood supply from the hepatic artery and portal vein, interruption of the flow through the hepatic artery was demonstrated to be safe in patients. Tumor embolization eventually developed, blocking the vascular supply to a tumor by primarily endovascular approaches. The application of angiography with embolization followed, and the administration of chemotherapeutic agents with embolic particles evolved into transcatheter arterial chemoembolization.[5]

    References

  2. Miraglia R, Pietrosi G, Maruzzelli L, et al. (2007). "Efficacy of transcatheter embolization/chemoembolization (TAE/TACE) for the treatment of single hepatocellular carcinoma". World J Gastroenterol. 13 (21): 2952–5. doi:10.3748/wjg.v13.i21.2952.
  3. Rammohan A, Sathyanesan J, Ramaswami S, et al. (2012). "Embolization of liver tumors: Past, present and future". World J Radiol. 4 (9): 405–12. doi:10.4329/wjr.v4.i9.405. PMC 3460228Freely accessible. PMID 23024842.
  4. Brown DB, Geschwind JF, Soulen MC, Millward SF, Sacks D (2006). "Society of Interventional Radiology position statement on chemoembolization of hepatic malignancies". J Vasc Interv Radiol. 17 (2): 217–23. doi:10.1097/01.rvi.0000196277.76812.a3.
  5. Stuart K (2003). "Chemoembolization in the management of liver tumors". Oncologist. 8 (5): 425–37. doi:10.1634/theoncologist.8-5-425.
  6. Guan YS, He Q, Wang MQ (2012). "Transcatheter arterial chemoembolization: history for more than 30 years". ISRN Gastroenterol.
Therapeutic intervention: 

High Dose Intravenous Vitamin C

field_vote: 

Vitamin C, when administered in high doses by intravenous (I.V.) infusions, can kill cancer cells. Vitamin C interacts with iron and other metals to create hydrogen peroxide. In high concentrations, hydrogen peroxide damages the DNA and mitochondria of cancer cells and shuts down their energy supply and kills them outright.

Best of all — and unlike virtually all conventional chemotherapy drugs that destroy cancer cells — it is selectively toxic. No matter how high the concentration, Vitamin C does not harm healthy cells.

Do not attempt to use this treatment by yourself. This treatment must be used under the direction of cancer experts who are based at a clinic. The Vitamin C by I.V. treatment is generally used for cancer, but it can also be used to cure MDM-1, NDM-1, and Ebola.

Clinics that offer
IV Vitamin C

Cancer Tutor Verified

 
 
 

Two-time Nobel Prize winner Linus Pauling, along with Dr. Ewen Cameron of Scotland, did a scientific study proving that 10 grams of Vitamin C, given by I.V., could extend the life of advanced cancer patients six-fold.

However, there is currently an entire field of research called orthomolecular medicine which is devoted to natural treatments, especially Vitamin C, and their effect on disease.

“Vitamin C is thought to act as a pro-oxidant inside the cell in high concentration, and some hydrogen peroxide is formed which is rapidly disposed of by catalase in a normal cell,” said Dr. William Wassell. “Since cancer cells have a deficiency or lack entirely of catalase the peroxides kill the [cancer] cell.”

There are several clinics in the United States that use this treatment. Bright Spot For Health, a large research clinic in Wichita, Kansas, was the home of a great deal of research on Vitamin C by I.V. The original research was done by the late Dr. Hugh Riordon.

In cancer, Riordan et al. (1995) demonstrated the likelihood that Vitamin C was an effective anti-tumor therapy as long as high enough concentrations of it could be achieved inside the tumor(s). These researchers also concluded that oral Vitamin C supplementation was unlikely to produce blood levels of Vitamin C high enough to have a direct killing effect on a given tumor.

Later, in studying a certain line of cancer cells and the ability of Vitamin C to kill those cancer cells, Casciari et al. (2001) elegantly demonstrated this point. They showed that the rapid intravenous infusion of Vitamin C as sodium ascorbate in combination with alpha-lipoic acid was effective in reaching Vitamin C levels that were toxic to the cancer cells. They also showed that a fat-soluble analogue of Vitamin C, phenyl-ascorbate, was able to kill cancer cells effectively at a dose roughly three times lower than seen with unaltered Vitamin C.

Vitamin C was first suggested as a tool for cancer treatment in the 1950s. Its role in collagen production and protection led scientists to hypothesize that ascorbate replenishment would protect normal tissue from tumor invasiveness and metastasis (McCormick, 1959; Cameron, et al., 1979). Also, since cancer patients are often depleted of vitamin C (Hoffman, 1985; Riordan, et al., 2005), replenishment may improve immune system function and enhance patient health and well-being (Henson, et al., 1991).

Cameron and Pauling observed fourfold survival times in terminal cancer patients treated with intravenous ascorbate infusions followed by oral supplementation (Cameron & Pauling, 1976). However, two randomized clinical trials with oral ascorbate alone conducted by the Mayo clinic showed no benefit (Creagan, et al., 1979; Moertel, et al., 1985). Most research from that point on focused on intravenous ascorbate. The rationales for using intravenous ascorbate infusions (IVC) to treat cancer:

  • Plasma ascorbate concentrations in the millimolar range can be safely achieved with IVC infusions.
  • At millimolar concentrations, ascorbate is preferentially toxic to cancer cells in vitro and is able to inhibit angiogenesis in vitro and in vivo.
  • Vitamin C can accumulate in tumors, with significant tumor growth inhibition seen (in guinea pigs) at intra-tumor concentrations of 1 mM or higher.
  • Published case studies report anti-cancer efficacy, improved patient well-being and decreased markers of inflammation and tumor growth.
  • Phase I clinical studies indicate that IVC can be administered safely with relatively few adverse effects.

If large amounts of Vitamin C are presented to cancer cells, large amounts will be absorbed. In these unusually large concentrations, the antioxidant Vitamin C will start behaving as a pro-oxidant as it interacts with intracellular copper and iron. This chemical interaction produces small amounts of hydrogen peroxide.

Because cancer cells are relatively low in the intracellular antioxidant enzyme catalase, the high dose Vitamin C induction of peroxide will continue to build up until it eventually lysis the cancer cell from the inside out. This effectively makes high dose IVC a non-toxic chemotherapeutic agent that can be given in conjunction with conventional cancer treatments. Based on the work of several Vitamin C pioneers before him, Dr. Riordan was able to prove that Vitamin C was selectively toxic to cancer cells if given intravenously. This research was reproduced and published by Dr. Mark Levine at the National Institutes of Health.

Only markedly higher doses of Vitamin C will selectively build up as peroxide in the cancer cells to the point of acting in a manner similar to chemotherapy. These tumor-toxic dosages can only be obtained by intravenous administration.

Therapeutic Substance(s): 
Disease(s): 

Hyperthermia

field_vote: 

From https://www.cancer.gov/about-cancer/treatment/types/surgery/hyperthermia-fact-sheet

Hyperthermia in Cancer Treatment

  • What is hyperthermia?

  • How is hyperthermia used to treat cancer?

  • What are the different methods of hyperthermia?

  • Does hyperthermia have any complications or side effects?

  • What does the future hold for hyperthermia?

What is hyperthermia?

Hyperthermia (also called thermal therapy or thermotherapy) is a type of cancer treatment in which body tissue is exposed to high temperatures (up to 113°F). Research has shown that high temperatures can damage and kill cancer cells, usually with minimal injury to normal tissues (1). By killing cancer cells and damaging proteins and structures within cells (2), hyperthermia may shrink tumors.

Hyperthermia is under study in clinical trials (research studies with people) and is not widely available.

How is hyperthermia used to treat cancer?

Hyperthermia is almost always used with other forms of cancer therapy, such as radiation therapy and chemotherapy (1, 3). Hyperthermia may make some cancer cells more sensitive to radiation or harm other cancer cells that radiation cannot damage. When hyperthermia and radiation therapy are combined, they are often given within an hour of each other. Hyperthermia can also enhance the effects of certain anticancer drugs.

Numerous clinical trials have studied hyperthermia in combination with radiation therapy and/or chemotherapy. These studies have focused on the treatment of many types of cancer, including sarcoma, melanoma, and cancers of the head and neck, brain, lung, esophagus, breast, bladder, rectum, liver, appendix, cervix, and peritoneal lining (mesothelioma) (1, 3–7). Many of these studies, but not all, have shown a significant reduction in tumor size when hyperthermia is combined with other treatments (1, 3, 6, 7). However, not all of these studies have shown increased survival in patients receiving the combined treatments (3, 5, 7).

What are the different methods of hyperthermia?

Several methods of hyperthermia are currently under study, including local, regional, and whole-body hyperthermia (1, 39).

  • In local hyperthermia, heat is applied to a small area, such as a tumor, using various techniques that deliver energy to heat the tumor. Different types of energy may be used to apply heat, including microwave, radiofrequency, and ultrasound. Depending on the tumor location, there are several approaches to local hyperthermia:
    • External approaches are used to treat tumors that are in or just below the skin. External applicators are positioned around or near the appropriate region, and energy is focused on the tumor to raise its temperature.
    • Intraluminal or endocavitary methods may be used to treat tumors within or near body cavities, such as the esophagus or rectum. Probes are placed inside the cavity and inserted into the tumor to deliver energy and heat the area directly.
    • Interstitial techniques are used to treat tumors deep within the body, such as brain tumors. This technique allows the tumor to be heated to higher temperatures than external techniques. Under anesthesia, probes or needles are inserted into the tumor. Imaging techniques, such as ultrasound, may be used to make sure the probe is properly positioned within the tumor. The heat source is then inserted into the probe. Radiofrequency ablation (RFA) is a type of interstitial hyperthermia that uses radio waves to heat and kill cancer cells.
  • In regional hyperthermia, various approaches may be used to heat large areas of tissue, such as a body cavity, organ, or limb.
    • Deep tissue approaches may be used to treat cancers within the body, such as cervical or bladder cancer. External applicators are positioned around the body cavity or organ to be treated, and microwave or radiofrequency energy is focused on the area to raise its temperature.
    • Regional perfusion techniques can be used to treat cancers in the arms and legs, such as melanoma, or cancer in some organs, such as the liver or lung. In this procedure, some of the patient’s blood is removed, heated, and then pumped (perfused) back into the limb or organ. Anticancer drugs are commonly given during this treatment.
    • Continuous hyperthermic peritoneal perfusion (CHPP) is a technique used to treat cancers within the peritoneal cavity (the space within the abdomen that contains the intestines, stomach, and liver), including primary peritoneal mesothelioma and stomach cancer. During surgery, heated anticancer drugs flow from a warming device through the peritoneal cavity. The peritoneal cavity temperature reaches 106-108°F.
  • Whole-body hyperthermia is used to treat metastatic cancer that has spread throughout the body. This can be accomplished by several techniques that raise the body temperature to 107-108°F, including the use of thermal chambers (similar to large incubators) or hot water blankets.

The effectiveness of hyperthermia treatment is related to the temperature achieved during the treatment, as well as the length of treatment and cell and tissue characteristics (1, 2). To ensure that the desired temperature is reached, but not exceeded, the temperature of the tumor and surrounding tissue is monitored throughout hyperthermia treatment (3, 5, 7). Using local anesthesia, the doctor inserts small needles or tubes with tiny thermometers into the treatment area to monitor the temperature. Imaging techniques, such as CT (computed tomography), may be used to make sure the probes are properly positioned (5).

Does hyperthermia have any complications or side effects?

Most normal tissues are not damaged during hyperthermia if the temperature remains under 111°F. However, due to regional differences in tissue characteristics, higher temperatures may occur in various spots. This can result in burns, blisters, discomfort, or pain (1, 5, 7). Perfusion techniques can cause tissue swelling, blood clots, bleeding, and other damage to the normal tissues in the perfused area; however, most of these side effects are temporary. Whole-body hyperthermia can cause more serious side effects, including cardiac and vascular disorders, but these effects are uncommon (1, 3, 7). Diarrhea, nausea, and vomiting are commonly observed after whole-body hyperthermia (7).

What does the future hold for hyperthermia?

A number of challenges must be overcome before hyperthermia can be considered a standard treatment for cancer (1, 3, 6, 7). Many clinical trials are being conducted to evaluate the effectiveness of hyperthermia. Some trials continue to research hyperthermia in combination with other therapies for the treatment of different cancers. Other studies focus on improving hyperthermia techniques.

To learn more about clinical trials, call NCI’s Cancer Information Service (CIS) at 1–800–4–CANCER (1–800–422–6237) or visit Clinical Trials Information for Patients and Caregivers.

 

Selected References
  1. van der Zee J. Heating the patient: a promising approach? Annals of Oncology 2002; 13(8):1173–1184. [PubMed Abstract]
  2. Hildebrandt B, Wust P, Ahlers O, et al. The cellular and molecular basis of hyperthermia. Critical Reviews in Oncology/Hematology 2002; 43(1):33–56. [PubMed Abstract]
  3. Wust P, Hildebrandt B, Sreenivasa G, et al. Hyperthermia in combined treatment of cancer. The Lancet Oncology 2002; 3(8):487–497. [PubMed Abstract]
  4. Alexander HR. Isolation perfusion. In: DeVita VT Jr., Hellman S, Rosenberg SA, editors. Cancer: Principles and Practice of Oncology. Vol. 1 and 2. 6th ed. Philadelphia: Lippincott Williams and Wilkins, 2001.
  5. Falk MH, Issels RD. Hyperthermia in oncology. International Journal of Hyperthermia 2001; 17(1):1–18. [PubMed Abstract]
  6. Dewhirst MW, Gibbs FA Jr, Roemer RB, Samulski TV. Hyperthermia. In: Gunderson LL, Tepper JE, editors. Clinical Radiation Oncology. 1st ed. New York, NY: Churchill Livingstone, 2000.
  7. Kapp DS, Hahn GM, Carlson RW. Principles of Hyperthermia. In: Bast RC Jr., Kufe DW, Pollock RE, et al., editors. Cancer Medicine e.5. 5th ed. Hamilton, Ontario: B.C. Decker Inc., 2000.
  8. Feldman AL, Libutti SK, Pingpank JF, et al. Analysis of factors associated with outcome in patients with malignant peritoneal mesothelioma undergoing surgical debulking and intraperitoneal chemotherapy. Journal of Clinical Oncology 2003; 21(24):4560–4567. [PubMed Abstract]
  9. Chang E, Alexander HR, Libutti SK, et al. Laparoscopic continuous hyperthermic peritoneal perfusion. Journal of the American College of Surgeons 2001; 193(2):225–229. [PubMed Abstract]

Immune Treatments

field_vote: 

These treatments intend to treat cancer and other diseases by modifying immune function.

Albarin, Injectable Aloe Vera or Polymannons

field_vote: 

 

from http://www.iahf.com/usa/20011106.html

To: "Health Freedom, Codex Issues
Subject: FDA RAID FLORIDA ALTERNATIVE CANCER CLINICS - TREATMENT BLOCKED -LIVES JEOPARDIZED
From: John Hammell jham@iahf.com
Date: Tue, 6 Nov 2001 13:43:35 -0500 (EST)

IAHF Webmaster: Breaking News, Create New Category: FDA ALBARIN RAIDS

IAHF LIST: The reason you haven't heard from me lately is because I am on the road in St.Petersburg FL assisting The Medical Center for Preventive and Nutritional Medicine of Tampa/St.Pete which got raided by the FDA Oct.11 placing several patients lives in jeopardy.In this article you will learn of the suppression of a remarkable injectable aloe vera treatment. Please help by taking the action steps requested at the end of my article.Please forward this to more people, and if you can help get Joe DiStephano on the air, please let me know. Urgent legal donations are needed by the clinic.

FDA TERRORISTS RAID FLORIDA ALTERNATIVE CLINICS
TREATMENT BLOCKED-LIVES JEOPARDIZED

By John C. Hammell, President, International Advocates for Health Freedom
http://www.iahf.com POB 625 Floyd V A 24091 USA 800-333-2553

On October 11,2001 120 terrorists from the Food and Drug Administration, Florida Department of Law Enforcement, and the Hillsborough County Sheriff's Office raided alternative cancer clinics in Tampa and St.Petersburg Florida run under the auspices of The Medical Center for Preventative and Nutritional Medicine. Ironically, the raids came exactly one month after the terrorist attack on the World Trade Center/Pentagon, they were conducted by our own government.

What sets this raid apart from other FDA raids is that 80 % of the cancer patients coming to the clinics for treatment with Albarin, an injectable form of Aloe Vera, were going into remission and not a single complaint came from a patient. The only complaints came from mainstream oncologists obviously solely interested in protecting their economic turf. Many patients lives have been thrown into disarray and several will be dead within a month if they can't get their Albarin back.

If the FDA succeeds in this outrageous effort to suppress patient's access to Albarin, consumers may never again have access to any unapproved treatment they may wish to use, no matter how good it may be. It is essential that everyone take the actions suggested at the end of this article to defend the lives of the patients.

Along with the Tampa and St.Petersburg clinics, the FDA raided the home of Joseph DiStefano, the licensed nutrition counselor who ran them in conjunction with Daniel Mayer, D.O. Their first 100 patients all came from Hospice where they'd been told they only had 2-3 months to live.DiStefano and Mayer only lost 6 out of lOO of them.

Although Albarin is not an FDA approved drug, DiStefano and Mayer had been conducting an INR investigation for its developer, Ivan Danhof, MD, PhD of the N Texas Research Laboratory, Grand Prairie, TX into its uses in the treatment of pain in prostate cancer. Danhof had filed an application for an Investigational New Drug (IND) and was on the verge of providing the FDA with data to support this application, when the raid occurred. They were prepared with solid clinical data from over 30 patients charts to prove that Albarin has a powerful immune enhancing effect while blocking the blood supply to cancer cells, causing rapid diminishing of their size and killing them.

Instead of storming in with this raid which is now jeopardizing lives, the FDA should have simply visited the clinics for the sake of friendly communication to find out what DiStefano, Mayer and Danhof were doing to make sure they were acting in compliance with the law. By conducting this Nazi styled raid, the FDA has grossly violated their mandate to safeguard the public health and they've betrayed our trust. Instead of protecting the public in this case, their actions are directly threatening people's lives.

US Attorney's Office spokesman Steve Cole would not comment on the investigation and U.S. Judge Thomas Mc Coun III sealed the search warrant affidavits used to justify the search warrants for 120 days, as the government seeks to cook up some "justification" for this illegal fishing expedition.

Judging from what was said during the raid, the trumped up charges will most likely include dispensing unapproved drugs, and for Joe DiSteffano, practicing medicine without a license. This charge against DiSteffano is absurd because he has never held himself out to be a doctor, he's been legally working for 38 years as a licensed nutrition counselor always alongside a licensed medical practitioner, in this case, Mayer, an osteopath.

DiSteffano's patients know he is not a doctor, but many of them affectionately call him "Dr Joe" as a term of respect and appreciation. I didn't meet a single unhappy patient here, they all have nothing but praise for DiSteffano and Mayer stating that they don't charge a cent for their initial consultations, and only charge $1100 for Albarin treatment, no matter how many times they have to come back for treatments and they have always been quite willing to work with their patients financially, turning NO ONE away due to any inability to pay. ($1100. is far less than what mainstream oncologists typically charge for a weeks worth of chemotherapy.)

DiStefano and Mayer are without question two of the kindest, most altruistic men I've ever met. Now that they have been raided, they're in desperate need of donations for their legal fund because they aren't making much money at all running these clinics where the primary focus has been to simply help people, not to make money.

Paul Schebell, Margaret Marsh, Karen Kyper, Ruth Hannah, Will Weinand, James Strickland, Robert Banks, and Robert Scofield are among the terminally ill cancer patients who have just been issued death sentences by the Food and Drug Administration Their medical records were seized in the raid, along with Albarin, and your help is urgently needed to defend their lives in the face of this insanity. They could all be dead soon unless they can resume Albarin treatment.

MIDNIGHT FDA DUMPSTER DIVERS CAUGHT TRESPASSING ONE WEEK BEFORE RAID

This FDA fishing expedition began a week before the raid when DiStefano exited his office at midnight only to catch FDA Senior Special Agent Rande Mattison and another FDA accomplice trespassing on clinic property, illegally rummaging through his dumpster with rubber gloves on. Trespassing this way was an immense screw up on the part of Mattison who failed to notice DiStefano's car parked in the clinic parking lot and so wrongly believed no one was there.

When DiStefano demanded to know what they thought they were doing trespassing on his property, they had the nerve to tell him they were merely "searching for boxes." "Sure you are, with rubber gloves on at midnight- everyone ALWAYS looks for boxes with rubber gloves on at midnight, you can't legally come on my property without a search warrant, do you have one?" DiStefano proceeded to write down their license plate number while telling them he was going to call the police. "Good" Mattison sneered. They were about to drive away when DiStefano demanded that they put back all the garbage they had removed from the dumpster, but Mattison scowled and tersely informed him that they didn't have to, but his partner said "yes, we do" and he put all the garbage back. Mattison peeled out of the driveway. On the day of the raid in which all Albarin, and patients charts were seized, Mattison pulled DiSteffano aside and told him they were going to "get him" for "practicing medicine without a license."

FEDS TAMPERED WITH CLINICS MAIL -BLOCKED KEY DATA FROM BEING SENT (?)

Shortly before the raid, when DiStefano attempted to mail over 30 patient charts with carefully presented data intended to be used by Ivan Danhof, MD, PhD the Texas researcher who had spent over 30 years developing Albarin to apply for a compassionate use IND, the box was mysteriously RETURNED to him marked "refused by addressee." Danhof never received the package, and he and DiStefano now speculate that the FDA may have been monitoring their mail and that they may have blocked Danhof's receipt of the data as part of their ongoing effort to block public access to this highly successful alternative cancer treatment.

DiSteffano's mail was routinely 3 days late in arriving, and took an extra 3 days to be sent anywhere. His mailman told him that it was being held, but he didn't know why.

Will this terrorist attack soon be another documented case of government genocide as the FDA continues to flaunt their mandate to protect the public health while providing a protection racket defending the profits of such mainstream oncology centers as the Moffitt Cancer Center in Tampa Florida?

A week ago I flew to Tampa from Virginia on the urgent request of the Life Extension Foundation to write this article and to do anything possible to assist in the fight back. Having interviewed several patients, and reviewed their medical records, I am horrified by what the FDA has done here. Every Wednesday since the raid, DiStefano's patients have held rallies in front of the Federal Courthouse in Tampa, and I went with them last Wednesday to take pictures and help carry a sign reading "FDA- Give Us Our Albarin Back" Unless the Courts and Congress rapidly intercede to restore these patients access to Albarin, many patients will be dead quite soon, and many more others who had gone into complete remission will see their cancers return.

WHAT IS ALBARIN?

Ivan Danhof; MD, PhD, the developer of Albarin, is regarded by many to be the leading authority on the aloe vera plant. Working out of the North Texas Research Laboratory in Grand Prairie, TX, Danhof has impeccable credentials B.S in biochemistry, M.S in Nutrition and Microbiology, PhD in Physiology, and an MD with specialties in Internal Medicine and Gastroenterology. He has written 80 research papers throughout his career. Additionally, he has served as a Fulbright scholar in Afghanistan investigating Botanical medicine.

Danhof states that the Aloe Vera mucilaginous polysaccharide is a long chain sugar molecule composed of individual mannose and glucose sugar molecules connected together. There is a wide range in the size of the mucilaginous polysaccharide molecule, and their size determines their healing properties. Albarin consists of very large particles. up to 9000 molecules which are extracted through a patented freeze drying process turning them into a powder, which was then turned into an intravenously applied liquid by a compounding pharmacist. These large molecules are immune modulating, and have a very powerful healing effect on AIDS, Cancer, and many other immune system disorders. This large molecule also causes the body to produce a natural chemical tumor necrosis factor that functions to shut off the blood supply to tumors.

Illustrating the wide range of healing applications of aloe, Danhof states that the small particles. 60-600 molecules reduce inflammation- which is involved in such diseases as ulcerative colitis, arthritis, and gastric reflux. The small particles also help with the reduction of blood sugar in Type I and II diabetes.

Medium sized particles, up to 1500 molecules, are very effective intracellular antioxidants and free radical scavengers. Whereas vitamins and minerals only have antioxidant properties outside the cells, aloe works within the cells to prevent and treat arteriosclerosis, heart disease, and Parkinson's disease. With the ever increasing pollution of the soil, the increase in free radicals and loss of cellular oxygen will only get worse over time. This makes Aloe Vera mucilaginous polysaccharides more important than ever.

Large sized particles, up to 5000 molecules have a direct antibacterial and anti viral effect. This is important with all the new infectious diseases cropping up and older ones becoming more virulent from long term use of antibiotics.

As stated above, the Albarin serum is derived from the largest particles, up to 9000 molecules in size.

MANUFACTURING PROCESS CRITICAL WITH ALOE

The mucilaginous polysaccharide molecule is very fragile. When the leaf of the aloe plant is cut, enzymes in the plant are released, which breaks down the long chain sugars of the mucilaginous polysaccharide into simple sugars, which then results in a loss of the different healing properties. There are very few products on the market that can claim to contain stabilized mucilaginous polysaccharides. Stabilization requires extraction of the musilaginous polysaccharides in a freeze-dried form but also the process must include a way to deactivate the enzymes released in the plant when it is cut. Furthermore, the high concentration of mineral salts found in Aloe Vera gel must be separated from the final extract because they are very irritating to the gut. An aloe product must be very soothing to the gut to promote healing.

Synergism is a property that many of the large Aloe companies tout who do not have the patented technology to extract stabilized mucilaginous polysaccharides. In other words, many of these companies claim that all 100 of the various ingredients found in Aloe Vera must be present for healing to occur. None of these claims have any basis in scientific research, while there is an abundance of research to prove that the mucilaginous polysaccharide is the sole ingredient responsible for all the healing properties attributed to Aloe.

CANCER RESEARCH on ALOE VERA/ALBARIN

Research by the immunologist Ian Tizard, PhD and virologist Maurice Kemp, PhD from Texas A&M led to the discovery that Aloe mucilaginous polysaccharide is taken into a special leukocyte, the macrophage, and this cell is stimulated to release messenger molecules called cytokines (interferons, interleukines, prostaglandins, tumor necrosis factor and stem cell growth factors. )

Tumors release a chemical that attracts blood circulation so that malignant cells have a supply of nutrition and can keep multiplying. Tumor necrosis factor shuts off the blood supply to the tumor and therefor it dies. All of the immune modulating effects from Aloe contribute greatly to the prevention and healing of malignant cells.

Danhof's Albarin is being shown to successfully treat about 80% of all cancer patients at The Medical Center for Preventative and Nutritional Medicine, and it is criminal that the FDA has seized the Albarin.

(How likely is the FDA to grant an IND given this raid? Typically, the FDA will grant an IND if one in 50 patients respond favorably to a new treatment. DiStefano has had an 80% success rate with Albarin, and it is apparent that many mainstream oncologists fear it as unwanted economic competition- the complete Albarin treatment has only cost patients $1100., regardless of how many treatments may be needed. Thats less than a typical charge for a week's worth of chemotherapy.)

Joe DiStefano started with the Albarin by successfully treating his own cancer. The first lOO patients he used it on all came from Hospice where they had been told they only had 2-3 months to live, and Joe only lost 6 out of 100 of them.

STATEMENTS FROM SELECTED PATIENTS

THREE WHO FACE IMMINENT DEATH SENTENCES IF CAN'T GET ALBARIN BACK And THREE OTHERS WHO's CANCER IS IN COMPLETE REMISSION WHO FEAR IT WILL NOW RETURN WITHOUT ALBARIN

PAUL SCHEBELL

Paul Schebell, 48, from Connecticut, Advanced Metastatic Prostate/Liver Cancer. Had onset in '98, was diagnosed by PSA levels and bonescan. Despite Lupron and hormone shots, the cancer kept progressing. Learning of the Albarin clinics through a chance phone call with a friend, he started on Albarin in July of 2001. Having been told death was imminent, he now feels much stronger mentally and physically. He can now walk much easier and can concentrate well enough to read. The only side effects from the Albarin are chills. He was stunned by the FDA raid saying "It would be almost ludicrous if not so tragic." He said that his chances will be "greatly diminished" if he can't get Albarin. When the FDA raided, he was receiving treatment and the FDA asked everyone if they wanted to stop. Not one hand went up, they all wanted to keep receiving treatment. Schebell was outraged and told them. "We're all adults here making free will choices."

Along with all the other people interviewed, Schebell stated that there had been no charge for the initial consultation, that the full Albarin treatment only cost $1100. No matter how many treatments were necessary. (He along with all patients stated that their mainstream treatment costs had been into the tens of thousands of dollars, some into the hundreds of thousands.) He (along with all patients) stated that at no time did Joe DiStefano ever hold himself out to be a doctor, they knew him to be a licensed nutrition counselor and they all stated that Daniel Mayer, DO was always present to advise them on their treatments. Schebell could be dead within a month unless he can keep getting his Albarin.

MARGARET MARSH

Peggy Marsh, 54 from Tampa Florida was diagnosed with Breast Cancer in '94. Diagnosis was made by biopsy, ultrasound, mammogram. She had a radical mastectomy, radiation, and chemo therapy through the Moffit Cancer Center in Tampa. She had 5 lymph nodes become cancerous by the time they did the open biopsy. After every chemo treatment she lay in bed for 5 days unable to move. They made her sick as a dog, very nauseated. The radiation caused multiple infections forcing her to constantly return to the hospital.

She had a grapefruit sized tumor in her liver a year and a half ago and was only given 6 months to live. She credits the Albarin with helping her to beat these odds. She was treated at the bone marrow clinic at Moffit Cancer Center in Tampa by Dr.Karen Fields, who ultimately issued an ultimatum- that she "had to trust" her medical expertise, and that she could only do either the albarin or chemo, but not both, even though Peggy wanted to keep using both and felt that both were vitally necessary in her case. Marsh, who was trained as a nutritionist and is a Cornell graduate, feels that this is an economic control issue, noting that "All of my Albarin treatments cost me only what one week of chemo costs now." She feels strongly that Moffit might be part of the complaint against Albarin to the FDA, and if that's the case, then Field's violated her trust. "I shared with her about the Albarin study, and if she initiated the complaint to the FDA, she is now jeopardizing not only my life, but the lives of all the patients taking Albarin." Marsh could be dead within a month if she can't keep getting her Albarin.

WILL WEINAND

Will Weinand, 54 from Chicago, started Albarin treatment in March of this year due to cancer in his prostate, spine, and hips. He had his prostate removed, but a year later discovered his cancer had spread to his spine and hips. He did hormone therapy and had severe pain in his lower spine at the T -4 and T -5 vertebrae The pain was so bad from this he had trouble getting out of bed and showering. Mainstream doctors told him he should have 21 days of radiation, and that he wouldn't live longer than a year. They told him the best they could do was pain management. After 6 weeks on the Albarin, the pain began to subside and was gone completely in 3 months. A recent MRI showed that the tumor between T -4 and T -5 vertebrae were gone, as well as the tumor in his left hip, but he still has cancer in his right hip and sacrum according to medical testing. He is very worried that the cancer will start spreading again without the Albarin, and is very disappointed that the government is strong arming their way in, stopping his Albarin treatment when it was clearly working. Will could be dead within a month if he can't resume his Albarin treatment.

PARI THIEM

Pari Thiern, 58 from Tampa FL had her thyroid removed due to cancer but still has lung and lymph node cancer which metastasized to the bone. She had a huge tumor on the left side of her neck that was going to choke her. After having her thyroid removed at McDill Airforce Base, they wanted to also remove the tumor in her neck and give her chemo and radiation. She refused having watched her first husband die from chemo and radiation, electing to try the Albarin after learning of the clinic at a local health food store via her son. Terrified that she could not afford the Albarin treatment, she was put at ease by Joe and Dr.Mayer who told her not to worry about the $1100. Cost, but to just begin her treatment which she did.

When she first started treatment she could not talk due to the tumor in her neck. She'd made four visits to the emergency room due to chronic infections which no antibiotics helped and was always sick with colds. The only side effects from the Albarin was coldness that went away shortly after each treatment. A catscan indicates that she is now free of cancer, and she is doing 100% better. She is terrified that her cancer will now return and pleads for the return of her Albarin saying "I can't believe this is happening in America."Greatly angered that her medical records were seized in the raid, she is now pleading for the President, her Senators and Congressmen to go to McDi11 Airforce base to look at her records and to see for himself how sick she was.

ROBERT BECKS

Robert Becks, 58 year old roofer from Clearwater, FL had a softball sized tumor in his neck which started growing 4 years ago and got enlarged a year and a half ago. It was diagnosed by cat scan, xrays and blood tests. It was too late for surgery, which would have been disfiguring. Holding the view that chemicals and radiation CAUSE cancer, it didn't make much sense to him to have mainstream treatments, which he refused. On December 12, 2000 he began Albarin treatment having learned of it by word of mouth. He was told the cost was $1100. which he could only partially afford to pay. He said Joe was "absolutely wonderful" about not pressing him financially and that he still owed the balance of his payment calling DiStefano and Mayer "The good guys with white hats."

Becks had 70 treatments, 4 per week and the Albarin "stopped the tumor right in its tracks". He said that for awhile he was too sick to resume treatments, and during that time the tumor started growing again, but went away again after treatment was resumed. He was able to stop taking morphine for pain due to the Albarin. Along with all the others interviewed, Becks stated that at no time did DiSteffano ever claim to be a doctor, but that he often called him "Doctor Joe" out of respect and appreciation. Along with all the others he stated that Dr.Mayer had always been present to consult on his treatment. Becks stated with regards to the raid. "This is crazy! I need my Albarin! I personally will do everything possible to get it back! The government has issued me a death sentence! Go look at the statistics, even the head of the Moffit Cancer Center did not take his own treatments when he got cancer, he used alternative treatment!"

MILES COOPER

Miles Cooper from Shelby NC is a gospel singer who has sung in the Grand Ole Opry in Nashville. He had stage 4 prostate cancer with enlarged lymph nodes and his prostate was pushed against his bladder. His PSA was 187 and he was told he had 6 months to a year to live. He learned of the Albarin treatment by word of mouth while discussing his cancer with friends at church and began treatment in April 2001. He had 86 treatments with Albarin and his PSA went from 187 to 0. 9 in 30 days. An MRI showed normal lymph nodes, and that his Prostate was beginning to shrink. Three weeks ago his PSA was 0.19, and his prostate was still shrinking. He is very concerned that without the Albarin his cancer, which is now in remission, will come back Miles is working very hard to help organize his fellow patients, as are several others. His quiet Christian faith is standing in good stead. He sincerely hopes that the courts and Congress will intercede to help get Albarin back, and that everyone reading this will help as well.

WHAT YOU CAN DO:

It is essential that everyone call their Senators and Congressmen to request an immediate oversight hearing of the FDA to force them to give the Albarin back to Joseph DiStefano and Dr.Mayer so that these patients can resume treatment. You can reach any member of congress via the Capital Switchboard at 202-225-3121. Especially be sure to call Congressman Dan Burton, Chair of the House Government Reform Committee. He had held other hearings to reign in the FDA and he must hold one very quickly to address this matter.

People living in St.Petersburg and Tampa should specifically call Rep Bill Young at 727-893-3191, and Rep Jim Davis at 813-354-9217 Tell them both that people have a right to freedom of choice in healthcare.

Post this on websites, and forward it to everyone you know- several people's lives are in direct jeopardy, and we must work together to help them get their Albarin back.

Forward this to radio and TV talk show hosts who can air this story If you can get Joe DiStefano onto any large radio or TV shows, contact him via The Medical Center for Preventive and Nutritional Medicine Inc.727-344-3134, 813-968-5998.

Badly needed donations for the legal fund for the Medical Center for Preventive and Nutritional Medicine can be made to:

Joe DiStefano Legal Defense Fund
c/o 6701-C 38th Ave. N.
St.Petersburg, FL 33710


 

Disease(s): 

Dendritic Cell Therapy

field_vote: 

DC Therapy

What is DC Therapy?

From https://dendritic.info/dc-therapy/

Dendritic Cell (DC) Therapy or so-called Dendritic Cell vaccine is a newly emerging and potent form of immune therapy used to treat cancer. Only recently (2010) approved by the US FDA, dendritic cell therapy is an immune therapy which harnesses the body’s own immune system to fight cancer. The dendritic cell itself is an immune cell whose role is the recognition, processing and presentation of foreign antigens to the T-cells in the effector arm of the immune system. Although dendritic cell are potent cells, they are not usually present in adequate quantity to allow for a potent immune response. Dendritic cell therapy thus involves the harvesting of blood cells (monocytes) from a patient and processing them in the laboratory to produce dendritic cells which are then given back to a patient in order to allow massive dendritic cell participation in optimally activating the immune system. To learn more about vaccine and dendritic cell therapy for cancer, please read the following articles:

The National Cancer Institute has a very concise primer on Treating and Preventing Cancer with Vaccines on their site.

Dendritic cells and immunity against cancer” by K. Palucka, H. Ueno1, J. Fay, and J. Banchereau of Baylor Institute for Immunology Research and Sammons Cancer Center, Baylor University Medical Center,Dallas, TX; and Department of Gene and Cell Medicine and Department of Medicine, Immunology Institute, Mount SinaiSchool ofMedicine, New York,NY,USA as published in Journal of Internal Medicine.

Volume 269, Issue 1, 2010.

Dendritic Cells (I): Biological functions” and “Dendritic Cells (II) Role and therapeutic implications in cancer” by S. Satthaporn and O. Eremin of the U. of Nottingham and Lincoln County Hospital, UK as published in J. of the Royal College Surgeons, Edinb.
46:9-20 and 159-167, 2001.

Clinical Applications of Dendritic Cell Cancer Vaccines” by Dr. Joseph Barr of the U. of Pittsburgh Cancer Institute, Pittsburgh, PA USA in The Oncologist 4(2): 140-144, 1999.

Also, a slide show / lecture presentation by Dr. Michael Morse on “Current Status of Dendritic-Cell Vaccines” is available on the Medscape site from WebMD as part of an educational session on “Therapeutic Cancer Vaccines: Targeting the Future of Cancer Treatment” but requires registration to enter the site.

There is also a youtube video presentation on “Using Dendritic Cells to Create Cancer Vaccines” by Professor Edgar Engleman of Standford University.

Abstracts of recent reviews on Pubmed include articles by IG Schmidt-Wolf et al. on “Dendritic Cell, the immunotherapeutic cell for cancer”, TL Whiteside and C Odous from U. of Pittsburgh Cancer Institute on “Dendritic cell biology and cancer therapy”, EM Hersh et al. on “Clinical Applications of dendritic cell vaccination in the treatment of cancer

Also, please refer to our Research Archives for many related abstracts on the therapy.

 

Therapeutic intervention: 

GcMAF-The cancer revolution from Japan

field_vote: 

From www.gcmaf.eu

GcMAF - treatment for cancer, aids and immune diseases

It is our immune system that prevents and cures cancer

A macrophage (purple) eats cancer cellsA macrophage (purple) eats cancer cells

The first research was published in 1993 and since then many papers have appeared indicating GcMAF cured Cancer and eradicated HIV by simply activating the immune system.

Dr. Nobuto Yamamoto in Philadelphia was the first, but hundreds of scientists have now worked on this and related projects.

How does GcMAF work?
In a healthy person GcMAF instructs macrophages in our bloodstream to scour our bodies and kill malignancies. But malignant cells like cancer send out an enzyme called Nagalase that neutralises the GcMAF; so the macrophages never get the message to go into action – in this way cancer suppresses the immune system, and cancer cells grow unchecked.

To reverse this, we make GcMAF outside the body, and it is injected once a week for 25 weeks for early cancers, 50 or more weeks for late stage cancers. (Encapsulated tumours require additional treatment.) HIV can require as little as 16 weeks.

In its role of immune system regulator, GcMAF reverses other diseases that attack the immune system like Osteoporosis, Aids, Hodgkin’s, Lupus, MS, Fibromyalgia, Parkinson’s, various bacterial and viral infections and various types of Immune dysfunction.

Small pre-clinical trials to build the case are again taking place.

Our GcMAF destroying human cancer cells for 72 hours. At 100ng/ml, panel D, cells show an irregular shape and size. They are significantly smaller as if processes of shrinkage had occurred. Cells appear inhomogeneous and both cytoplasm and nucleus appear irregular as if fragmented. Numerous cellular debris can be observed as well as apoptotic bodies. Clusters are much fewer in number and their borders appear less defined.Our GcMAF destroying human cancer cells for 72 hours. At 100ng/ml, panel D, cells show an irregular shape and size. They are significantly smaller as if processes of shrinkage had occurred. Cells appear inhomogeneous and both cytoplasm and nucleus appear irregular as if fragmented. Numerous cellular debris can be observed as well as apoptotic bodies. Clusters are much fewer in number and their borders appear less defined.

Those diagnosed with any of these illnesses, and who have done their own research on it,  are invited to respond. We ask for a copy of diagnostic information and update reports from a physician during and after treatments, to help build the case that GcMAF is a cure for various illnesses, which will help to make it available to the public. Participants are free to stop at any time.

What have we learned?

Dr Yamamoto carefully selected his trials: he took fit people with in the early stages of cancer and HIV, and reported 100% success, with no recurrence after many years. He did not attempt to cure people with large tumours.

Our trials are quite different: most people are over 50, some over 70, with advanced or terminal cancers, with significant tumour mass.

We appear to have had stunning results in 20 percent of cases, and we think we have learned enough to take that figure up to 50% in this 2011 round of trials. GcMAF needs normal levels of vitamin D to function strongly, and those participants see significant tumour shrinkage in 8 weeks. But even in low responders, GcMAF appears to stop the advance of cancer.

We have probably proved GcMAF can work for people up to age 67, with terminal stage 4 cancer, and can completely destroy large tumour mass.

So far those patients who in 8 weeks are cured of symptoms, or whose tumour mass drops significantly, all take exercise, perhaps a 40 minute walk outside each day.

HIV participants should expect to see viral loads drop to zero, and CD4 counts rise by at least 300 points in 16 weeks, and if that doesn't happen we will refund your money.

But the beauty of using your own immune system to cure cancer is that it remembers how to defeat it for the rest of your life: it doesn't come back. And unlike chemotherapy, the side effects are trivial.

Therapeutic Substance(s): 

Low Dose naltrexone

field_vote: 

Low Dose Naltrexone

 

LDN: Editor's Blog

Major International Progress — Oct 2016

Immune Therapeutics, Inc. has vigorous plans for its Lodonal brand of LDN‬

At its recent stockholders meeting, the company announced ‪its intention to seek approval of Lodonal by the United Nations, the President’s Emergency Plan for AIDS Relief, and UNAIDS. In addition, it is awaiting a meeting with the FDA to discuss plans for a trial of Lodonal for Crohn’s Disease.

Click here to learn more about plans for Africa and elsewhere...

 


FDA-approved naltrexone, in a low dose, can normalize the immune system — helping those with HIV/AIDS, cancer, autoimmune diseases, and central nervous system disorders.


 

Welcome to the Low Dose Naltrexone (LDN) Home Page

 

Updated: Oct 17, 2016

The authors of this website do not profit from the sale of low-dose naltrexone or from website traffic, and are in no way associated with any pharmaceutical manufacturer or pharmacy.

[Your user agent does not support frames or is currently configured not to display frames. Instead, &lt;A href="nav.htm"&gt;click here&lt;/A&gt; for buttons to help navigate this website.]

 

For announcements and discussion about Low Dose Naltrexone,
subscribe to the LDN Yahoo Group:


The LDN Yahoo Group is an announcement and discussion group for those interested in LDN, and who wish to be notified about updates to this website. We expect that official announcements to the group will be fairly infrequent, typically not more than one per month. Group members not wishing to receive general discussion e-mail from other members may set their message delivery option to "Special Notices" when joining, or by logging on to the LDN Yahoo Group site and clicking on "Edit My Membership."

 


 

“Low Dose Naltrexone (LDN) may well be the most important therapeutic breakthrough in over fifty years. It provides a new, safe and inexpensive method of medical treatment by mobilizing the natural defenses of one’s own immune system.

“LDN substantially reduces health care costs and improves treatment of a wide array of diseases. Unfortunately, because naltrexone has been without patent protection for many years, no pharmaceutical company will bear the expense of the large clinical trials necessary for FDA approval of LDN’s new special uses. It is now up to public institutions to seize the opportunity that LDN offers.”

  — David Gluck, MD


 

LDN: The Latest Research

International Journal of Oncology — June 2016

LDN Possesses Anticancer Activity

Wai M. Liu, Katherine A. Scott, et al of the Department of Oncology, St. George's University of London, report that they evaluated the gene expression profile of a cancer cell line after treatment with low-dose naltrexone (LDN), and that “our data support further the idea that LDN possesses anticancer activity.”

Click here to learn more...

 


LDN Website Contents

> On this page you can find answers to these questions:

> You can go to more detailed information on these linked pages:

 


 

CBS News Reports:
"Wonder drug" LDN Could Help Treat Cancer, Multiple Sclerosis

JACKSONVILLE, FLA (CBS) — February, 2008 — This report features an interview with Lori Miles, an MS sufferer who can now walk again, thanks to LDN. Also quoted in the piece is Dr. Daniel Kantor, neurologist and director of the Comprehensive Multiple Sclerosis Program at the Shands Jacksonville Neuroscience Institute: "I would like all of us to write to our congressmen, ask the FDA and NIH—National Institutes of Health—to fund more research about LDN."

 


What is low-dose naltrexone and why is it important?

> Low-dose naltrexone holds great promise for the millions of people worldwide with autoimmune diseases or central nervous system disorders or who face a deadly cancer.

> In the developing world, LDN could provide the first low-cost, easy to administer, and side-effect-free therapy for HIV/AIDS.

Naltrexone itself was approved by the FDA in 1984 in a 50mg dose for the purpose of helping heroin or opium addicts, by blocking the effect of such drugs. By blocking opioid receptors, naltrexone also blocks the reception of the opioid hormones that our brain and adrenal glands produce: beta-endorphin and metenkephalin. Many body tissues have receptors for these endorphins and enkephalins, including virtually every cell of the body's immune system.

In 1985, Bernard Bihari, MD, a physician with a clinical practice in New York City, discovered the effects of a much smaller dose of naltrexone (approximately 3mg once a day) on the body's immune system. He found that this low dose, taken at bedtime, was able to enhance a patient's response to infection by HIV, the virus that causes AIDS. [Note: Subsequently, the optimal adult dosage of LDN has been found to be 4.5mg.]

In the mid-1990's, Dr. Bihari found that patients in his practice with cancer (such as lymphoma or pancreatic cancer) could benefit, in some cases dramatically, from LDN. In addition, people who had an autoimmune disease (such as lupus) often showed prompt control of disease activity while taking LDN.


 

First Study of LDN Published
in US Medical Journal

Dr. Jill Smith’s original article, "Low-Dose Naltrexone Therapy Improves Active Crohn’s Disease," in the January issue of the American Journal of Gastroenterology (2007;102:1–9), officially presents LDN to the world of scientific medicine. Smith, Professor of Gastroenterology at Pennsylvania State University's College of Medicine, found that two-thirds of the patients in her pilot study went into remission and fully 89% of the group responded to treatment to some degree. She concluded that “LDN therapy appears effective and safe in subjects with active Crohn’s disease.” (For further information on Smith's study, please see the linked Clinical Trials page.)

Endoscopic Improvement in Crohn’s Colitis with Naltrexone
Figure A: Shown is the rectum of a subject with active Crohn’s Disease before starting therapy with naltrexone 4.5 mg/day. The mucosa is ulcerated, edematous, and inflamed.
Figure B: Shows the same area of the rectum in the same patient four weeks after naltrexone therapy. The lining is now healed, ulcers resolved, and the mucosa is healthy.
Copyrights: do not reproduce the above images and captions without written permission from Jill P. Smith, MD, Professor of Medicine, H-045 GI Division, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033

 


How does LDN work?

> LDN boosts the immune system, activating the body's own natural defenses.

Up to the present time, the question of "What controls the immune system?" has not been present in the curricula of medical colleges and the issue has not formed a part of the received wisdom of practicing physicians. Nonetheless, a body of research over the past two decades has pointed repeatedly to one's own endorphin secretions (our internal opioids) as playing the central role in the beneficial orchestration of the immune system, and recognition of the facts is growing.

Witness these statements from a review article of medical progress in the November 13, 2003 issue of the prestigious New England Journal of Medicine: "Opioid-Induced Immune Modulation: .... Preclinical evidence indicates overwhelmingly that opioids alter the development, differentiation, and function of immune cells, and that both innate and adaptive systems are affected.1,2 Bone marrow progenitor cells, macrophages, natural killer cells, immature thymocytes and T cells, and B cells are all involved. The relatively recent identification of opioid-related receptors on immune cells makes it even more likely that opioids have direct effects on the immune system.3"

The brief blockade of opioid receptors between 2 a.m. and 4 a.m. that is caused by taking LDN at bedtime each night is believed to produce a prolonged up-regulation of vital elements of the immune system by causing an increase in endorphin and enkephalin production. Normal volunteers who have taken LDN in this fashion have been found to have much higher levels of beta-endorphins circulating in their blood in the following days. Animal research by I. Zagon, PhD, and his colleagues has shown a marked increase in metenkephalin levels as well. [Note: Additional information for Dr. Zagon can be found at the end of this page.]

Bihari says that his patients with HIV/AIDS who regularly took LDN before the availability of HAART were generally spared any deterioration of their important helper T cells (CD4+).

In human cancer, research by Zagon over many years has demonstrated inhibition of a number of different human tumors in laboratory studies by using endorphins and low dose naltrexone. It is suggested that the increased endorphin and enkephalin levels, induced by LDN, work directly on the tumors' opioid receptors — and, perhaps, induce cancer cell death (apoptosis). In addition, it is believed that they act to increase natural killer cells and other healthy immune defenses against cancer.

In general, in people with diseases that are partially or largely triggered by a deficiency of endorphins (including cancer and autoimmune diseases), or are accelerated by a deficiency of endorphins (such as HIV/AIDS), restoration of the body's normal production of endorphins is the major therapeutic action of LDN.


 

ABC News Reports:
LDN a "Wonder Drug?"

By Ali Gorman

Hershey, Pa. - May 21, 2008 (WPVI) -- It's a drug already helping thousands of people battle addiction, but many people believe it also has the potential to help tens-of-thousands of patients with diseases like Crohn's, multiple sclerosis, Lupus, Parkinson's and even HIV.

It's called low dose naltrexone or LDN. Many patients who've tried it said it works and doesn't have bad side effects. But getting it to a pharmacy near you could be difficult. [Please click to read more. Video no longer available.]

 


What diseases has it been useful for and how effective is it?

> Bernard Bihari, MD, as well as other physicians and researchers, have described beneficial effects of LDN on a variety of diseases:

Cancers
  • Bladder Cancer
  • Breast Cancer
  • Carcinoid
  • Colon & Rectal Cancer
  • Glioblastoma
  • Liver Cancer
  • Lung Cancer (Non-Small Cell)
  • Lymphocytic Leukemia (chronic)
  • Lymphoma (Hodgkin's and Non-Hodgkin's)
  • Malignant Melanoma
  • Multiple Myeloma
  • Neuroblastoma
  • Ovarian Cancer
  • Pancreatic Cancer
  • Prostate Cancer (untreated)
  • Renal Cell Carcinoma
  • Throat Cancer
  • Uterine Cancer
Other Diseases
  • Common Colds (URI’s)
  • Emphysema (COPD)
  • HIV/AIDS
  • Depression (Major; and Bipolar)
  • Lyme Disease (LATE Stage)
Autoimmune

Neurodegenerative:
  • ALS (Lou Gehrig's Disease)
  • Alzheimer's Disease
  • Autism Spectrum Disorders
  • Hereditary Spastic Paraparesis
  • Multiple Sclerosis (MS)
  • Parkinson's Disease
  • Post-Polio Syndrome
  • Post-Traumatic Stress Disorder (PTSD) 
  • Primary Lateral Sclerosis (PLS)
  • Progressive Supranuclear Palsy
  • Transverse Myelitis

Other Autoimmune Diseases:
  • Ankylosing Spondylitis
  • Behcet's Disease
  • Celiac Disease
  • Chronic Fatigue Syndrome
  • CREST syndrome
  • Crohn's Disease
  • Dermatomyositis
  • Dystonia
  • Endometriosis
  • Fibromyalgia
  • Hashimoto’s Thyroiditis
  • Irritable Bowel Syndrome (IBS)
  • Myasthenia Gravis (MG)
  • Nephrotic Syndrome
  • Pemphigoid
  • Primary Biliary Cirrhosis
  • Psoriasis
  • Rheumatoid Arthritis
  • Sarcoidosis
  • Scleroderma
  • Sjogren’s Syndrome
  • Stiff Person Syndrome (SPS)
  • Systemic Lupus (SLE)
  • Ulcerative Colitis
  • Wegener's Granulomatosis

> LDN has demonstrated efficacy in thousands of cases.

Cancer. As of mid-2004, Dr. Bihari reported having treated over 300 patients who had a cancer that had failed to respond to standard treatments. Of that group, some 50%, after four to six months treatment with LDN, began to demonstrate a halt in cancer growth and, of those, over one-third have shown objective signs of tumor shrinkage.

Autoimmune diseases. Within the group of patients who presented with an autoimmune disease (see above list), none have failed to respond to LDN; all have experienced a halt in progression of their illness. In many patients there was a marked remission in signs and symptoms of the disease. The greatest number of patients within the autoimmune group are people with multiple sclerosis, of whom there were some 400 in Dr. Bihari's practice. Less than 1% of these patients has ever experienced a fresh attack of MS while they maintained their regular LDN nightly therapy.

HIV/AIDS. As of September 2003, Dr. Bihari had been treating 350 AIDS patients using LDN in conjunction with accepted AIDS therapies. Over the prior 7 years over 85% of these patients showed no detectable levels of the HIV virus — a much higher success rate than most current AIDS treatments, and with no significant side effects. It is also worth noting that many HIV/AIDS patients have been living symptom-free for years taking only LDN with no other medications.

Central Nervous System disorders. Anecdotal reports continue to be received concerning beneficial effects of LDN on the course of Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS—Lou Gehrig’s disease), and primary lateral sclerosis. Dr. Jaquelyn McCandless has found a very positive effect of LDN, in appropriately reduced dosage and applied as a transdermal cream, in children with autism.

> How is it possible that one medication can impact such a wide range of disorders?

The disorders listed above all share a particular feature: in all of them, the immune system plays a central role. Low blood levels of endorphins are generally present, contributing to the disease-associated immune deficiencies.

Research by others — on neuropeptide receptors expressed by various human tumors — has found opioid receptors in many types of cancer:

  • Brain tumors (both astrocytoma and glioblastoma)
  • Breast cancer
  • Endometrial cancer
  • Head and neck squamous cell carcinoma
  • Myeloid leukemia
  • Lung cancer (both small cell and non-small cell)
  • Neuroblastoma and others...

These findings suggest the possibility for a beneficial LDN effect in a wide variety of common cancers.


How can I obtain LDN and what will it cost?

> LDN can be prescribed by your doctor, and should be prepared by a reliable compounding pharmacy.

Naltrexone is a prescription drug, so your physician would have to give you a prescription after deciding that LDN appears appropriate for you.

Naltrexone in the large 50mg size, originally manufactured by DuPont under the brand name ReVia, is now sold by Mallinckrodt as Depade and by Barr Laboratories under the generic name naltrexone.

LDN prescriptions are now being filled by hundreds of local pharmacies, as well as by some mail-order pharmacies, around the US. Some pharmacists have been grinding up the 50mg tablets of naltrexone to prepare the 4.5mg capsules of LDN; others use naltrexone, purchased as a pure powder, from a primary manufacturer.

> LDN is not expensive.

One of the first pharmacies to compound LDN was Irmat Pharmacy in Manhattan. Their current price for a one month supply (30 capsules) of LDN is $45 dollars (for 4.0mg and greater; $37.50 for less than 4.0mg). Irmat does monthly quality control testing on its LDN, and will accept prescriptions from any licensed practitioner. No insurance is accepted. It can ship to the majority of states in the United States, but not internationally.

> Pharmacies that are known to be reliable compounders of LDN:

PharmacyPhoneFax
Irmat Pharmacy, New York, NY (212) 685-0502 (212) 532-6596
Belmar Pharmacy, Lakewood, CO (800) 525-9473 (866) 415-2923
The Compounder Pharmacy, Aurora, IL (630) 859-0333
(800) 679-4667
(630) 859-0114
The Pharmacy Shop and
Compounding Center, Canandaigua, NY
(585) 396-9970
(800) 396-9970
(585) 396-7264
McGuff Compounding Pharmacy,
Santa Ana, CA
(714) 438-0536
(877) 444-1133
(877) 444-1155
Skip's Pharmacy, Boca Raton, FL (561) 218-0111
(800) 553-7429
(561) 218-8873
The Medicine Store Pharmacy, Concord, NH (603) 225-2747
(877) 926-7637
(603) 224-3661
Smith's Pharmacy, Toronto, Canada (416) 488-2600
(800) 361-6624
(416) 484-8855
Dickson Chemist, Glasgow, Scotland +44-141-647-8032
+44-800-027-0673
+44-141-647-8032

 

IMPORTANT: Make sure to specify that you do NOT want LDN in a slow-release form.

Reports have been received from patients that their pharmacies have been supplying a slow-release form of naltrexone. Pharmacies should be instructed NOT to provide LDN in an "SR" or slow-release or timed-release form. Unless the low dose of naltrexone is in an unaltered form, which permits it to reach a prompt "spike" in the blood stream, its therapeutic effects may be inhibited.

Fillers. Capsules of LDN necessarily contain a substantial percentage of neutral inactive filler. Experiments by the compounding pharmacist, Dr. Skip Lenz, have demonstrated that the use of calcium carbonate as a filler will interfere with absorption of the LDN capsule. Therefore, it is suggested that calcium carbonate filler not be employed in compounding LDN capsules. He recommends either Avicel, lactose (if lactose intolerance is not a problem), or sucrose fillers as useful fast-release fillers.

> IMPORTANT: Make sure to fill your Rx at a compounding pharmacy that has a reputation for consistent reliability in the quality of the LDN it delivers.

The FDA has found a significant error rate in compounded prescriptions produced at randomly selected pharmacies. Dr. Bihari has reported seeing adverse effects from this problem. Please see our report, Reliability Problem With Compounding Pharmacies. Please see the above list of recommended pharmacies for some suggested sources.


What dosage and frequency should my physician prescribe?

The usual adult dosage is 4.5mg taken once daily at night. Because of the rhythms of the body's production of master hormones, LDN is best taken between 9pm and 3am. Most patients take it at bedtime.

Notable exceptions:

  • People who have multiple sclerosis that has led to muscle spasms are advised to use only 3mg daily and to maintain that dosage.
  • For intial dosage of LDN in those patients who have Hashimoto’s thyroiditis with hypothyroidism and who are taking thyroid hormone replacement medication, please read Cautionary Warnings, below.

Rarely, the naltrexone may need to be purchased as a solution — in distilled water — with 1mg per ml dispensed with a 5ml medicine dropper. If LDN is used in a liquid form, it is important to keep it refrigerated.

The therapeutic dosage range for LDN is from 1.5mg to 4.5mg every night. Dosages below this range are likely to have no effect at all, and dosages above this range are likely to block endorphins for too long a period of time and interfere with its effectiveness.

> IMPORTANT: Make sure to specify that you do NOT want LDN in a slow-release form (see above).


Are there any side effects or cautionary warnings?

> Side effects:

LDN has virtually no side effects. Occasionally, during the first week's use of LDN, patients may complain of some difficulty sleeping. This rarely persists after the first week. Should it do so, dosage can be reduced from 4.5mg to 3mg nightly.

> Cautionary warnings:

  1. Because LDN blocks opioid receptors throughout the body for three or four hours, people using medicine that is an opioid agonist, i.e. narcotic medication — such as Ultram (tramadol), morphine, dextromethorphan, Percocet, Duragesic patch or codeine-containing medication — should not take LDN until such medicine is completely out of one's system. Patients who have become dependant on daily use of narcotic-containing pain medication may require 10 days to 2 weeks of slowly weaning off of such drugs entirely (while first substituting full doses of non-narcotic pain medications) before being able to begin LDN safely.
  2. Those patients who are taking thyroid hormone replacement for a diagnosis of Hashimoto’s thyroiditis with hypothyroidism ought to begin LDN at the lowest range (1.5mg for an adult). Be aware that LDN may lead to a prompt decrease in the autoimmune disorder, which then may require a rapid reduction in the dose of thyroid hormone replacement in order to avoid symptoms of hyperthyroidism.
  3. Full-dose naltrexone (50mg) carries a cautionary warning against its use in those with liver disease. This warning was placed because of adverse liver effects that were found in experiments involving 300mg daily. The 50mg dose does not apparently produce impairment of liver function nor, of course, do the much smaller 3mg and 4.5mg doses.
  4. People who have received organ transplants and who therefore are taking immunosuppressive medication on a permanent basis are cautioned against the use of LDN because it may act to counter the effect of those medications.

When will the low-dose use of naltrexone become FDA approved?

> Although naltrexone itself is an FDA-approved drug, the varied uses of LDN still await application to the FDA after related scientific clinical trials.

The FDA approved naltrexone at the 50mg dosage in 1984. LDN (in the 3mg or 4.5mg dosage) has not yet been submitted for approval because the prospective clinical trials that are required for FDA approval need to be funded at the cost of many millions of dollars.

The successful results of the first US medical center research on LDN, an open-label trial that tested the use of LDN in Crohn’s disease (details here), was presented in May 2006 by Professor Jill Smith of the Pennsylvania State University College of Medicine. The National Institutes of Health has granted $500,000 for Dr. Smith's group to continue the study as a larger placebo-controlled scientific trial of LDN in Crohn's disease.

All physicians understand that appropriate off-label use of an already FDA-approved medication such as naltrexone is perfectly ethical and legal. Because naltrexone itself has already passed animal toxicity studies, one could expect that once testing is able to begin, LDN could complete its clinical trials in humans and receive FDA approval for one or more uses within two to four years.


What You Can Do

> Talk to your doctor.

If you are suffering from HIV/AIDS, cancer, or an autoimmune disease, LDN could help. In AIDS and cancer therapy, LDN is often used in conjunction with other medications.

Cancer. Anyone with cancer or a pre-cancerous condition should consider LDN. Many use LDN as a preventive treatment. Post-treatment, others have been using LDN to prevent a recurrence of their cancer. LDN has been shown in many cases to work with virtually incurable cancers such as neuroblastoma, multiple myeloma, and pancreatic cancer.

HIV/AIDS. As an AIDS drug, LDN leads to far fewer side effects than the standard "AIDS cocktail." When used in conjunction with HAART therapies, LDN can boost T-cell populations, prevent disfiguring lipodystrophy, and lower rates of treatment failure.

Do not be afraid to approach your doctors — physicians today are increasingly open to learning about new therapies in development. Tell your doctors about this website, or print out and hand them the information, and let them weigh the evidence.

> Tell others.

If someone you know has HIV/AIDS, cancer, an autoimmune disease, or one of the aforementioned central nervous system disorders, LDN could save them from a great deal of suffering. If they use e-mail, send them the address of this website (www.lowdosenaltrexone.org). Or, print out the site and mail them the information.

> Help spread the word to the media, the medical community, and to developing countries.

Low-dose naltrexone has the potential to reduce the terrible human loss now taking place throughout the globe. It is a drug that could prevent millions of children from becoming AIDS orphans. It is a drug that could be a powerful ally in the war against cancer.

If you or someone you know has connections in the media, the medical community, or to those in developing countries involved in AIDS policy or treatment, please let them know about LDN.


About This Website

> This is a not-for-profit website.

This website is sponsored by Advocates For Therapeutic Immunology. The purpose of this website is to provide information to patients and physicians about important therapeutic breakthroughs in advanced medical immunology. The authors of this site do not profit from the sale of low-dose naltrexone or from website traffic, and are in no way associated with any pharmaceutical manufacturer or pharmacy.

> Consult your doctor.

This website is not intended as a substitute for professional medical help or advice. A physician should always be consulted for any medical condition.

> Contact us.

For information on how to contact us with questions or comments, click here.

Please note that no response can be given to individual questions concerning medical symptoms or treatment.


Additional Information

  • Bernard Bihari, MD, was the discoverer of the major clinical effects of low dose naltrexone. A private practitioner in Manhattan, Dr. Bihari was a Board-certified specialist in Psychiatry and Neurology. Dr. Bihari's curriculum vitae.
  • David Gluck, MD (NY Lic. #083512), is the editor of this website, ldninfo.org. He is a Board-certified specialist in both Internal Medicine and Preventive Medicine. Dr. Gluck has served as medical director for JCPenney and MetLife, and is now semi-retired, living and working in New York City. [Ed. Note: Please do not confuse David Gluck, MD with an unrelated doctor of similar name in New York, David A. Gluck, who is a specialist in Obstetrics and Gynecology.]
  • Ian S. Zagon, PhD, has spent over two decades in doing basic research concerning endorphins. He is Professor of Neural and Behavioral Sciences, Pennsylvania State University, Dept. of Neural and Behavioral Sciences, H-109, Hershey Medical Center, Hershey, PA 17033; office phone: (717) 531-6409; email: isz1@psu.edu; website.

Footnotes

  1. Roy S, Loh HH. Effects of opioids on the immune system. Neurochem Res 1996;21:1375-1386
  2. Risdahl JM, Khanna KV, Peterson PK, Molitor TW. Opiates and infection. J Neuroimmunol 1998;83:4-18
  3. Makman MH. Morphine receptors in immunocytes and neurons. Adv Neuroimmunol 1994;4:69-82
Therapeutic Substance(s): 
Therapeutic intervention: 
Disease(s): 

Oncolytic Virus Treatment

field_vote: 

From Wikipeda:

Oncolytic virus Treatment

From Wikipedia, the free encyclopedia

An oncolytic virus is a virus that preferentially infects and kills cancer cells.[1][2] As the infected cancer cells are destroyed by oncolysis, they release new infectious virus particles or virions to help destroy the remaining tumour.[3][4] Oncolytic viruses are thought not only to cause direct destruction of the tumour cells, but also to stimulate host anti-tumour immune responses.[5][6]

The potential of viruses as anti-cancer agents was first realised in the early twentieth century, although coordinated research efforts did not begin until the 1960s.[7] A number of viruses including adenovirus, reovirus, measles, herpes simplex, Newcastle disease virus and vaccinia have now been clinically tested as oncolytic agents.[8] Most current oncolytic viruses are engineered for tumour selectivity, although there are naturally occurring examples such as reovirus and the senecavirus,[9] resulting in clinical trials.[10]

The first oncolytic virus approved by a national regulatory agency is genetically not modified ECHO-7 strain enterovirus RIGVIR, approved in Latvia in 2004 for treatment of skin melanoma.[11] Later (in 2015 and 2016 respectively) it was also approved in Georgia (country)[12] and Armenia. In 2005 Chinese company, Shanghai Sunway Biotech registered an oncolytic adenovirus, a genetically modified adenovirus named H101. It gained regulatory approval in 2005 from the CFDA, for the treatment of head and neck cancer.[13] The drug talimogene laherparepvec (OncoVex, T-VEC) was the first oncolytic herpes virus ( a modified herpes simplex virus), approved for use by the USFDA and by the EMA in the EU in 2015 for the treatment of advanced inoperable melanoma. In a combined decision, members of the FDA's Oncology Drug Advisory Committee and Cellular, Tissue and Gene Therapies Advisory Committee voted 22-1 to recommend approval of the oncolytic immunotherapy.[14]

Contents

History

A connection between cancer regression and viruses has long been theorised, and case reports of regression noted in cervical cancer, Burkitt lymphoma and Hodgkin lymphoma, after immunisation or infection with an unrelated virus appeared at the beginning of the 20th century.[15] Efforts to treat cancer through immunisation or virotherapy (deliberate infection with a virus), began in the mid-20th century.[15][16] As the technology for creating a custom virus did not exist, all early efforts focused on finding natural oncolytic viruses. During the 1960s, promising research involved using poliovirus,[17] adenovirus,[15] Coxsackie virus,[18] ECHO enterovirus RIGVIR[19] and others.[16] The early complications were occasional cases of uncontrolled infection, resulting in significant morbidity and mortality; the very frequent development of an immune response, while harmless to the patient,[15] destroyed the virus and thus prevented it from destroying the cancer.[17] Only certain cancers could be treated through virotherapy was also recognised very early.[18] Even when a response was seen, these responses were neither complete nor durable.[15] The field of virotherapy was nearly abandoned for a time, as the technology required to modify viruses didn't exist and chemotherapy and radiotherapy technology enjoyed early success. However, now these technologies have been thoroughly developed, cancer is still a major cause of mortality and there is still a need for novel cancer therapies, this sidelined therapy has now gained renewed interest.[15][20]

Herpes simplex virus

Herpes simplex virus (HSV) was one of the first viruses to be adapted to attack cancer cells selectively, because it was well understood, easy to manipulate and relatively harmless in its natural state (merely causing cold sores) so likely to pose fewer risks. The herpes simplex virus type 1 (HSV-1) mutant 1716 lacks both copies of the ICP34.5 gene, and as a result is no longer able to replicate in terminally differentiated and non-dividing cells but will infect and cause lysis very efficiently in cancer cells, and this has proved to be an effective tumour-targeting strategy.[21][22] In a wide range of in vivo cancer models, the HSV1716 virus has induced tumour regression and increased survival times.[23][24][25]

In 1996, the first approval was given in Europe for a clinical trial using the oncolytic virus HSV1716. From 1997 to 2003, strain HSV1716 was injected into tumours of patients with glioblastoma multiforme, a highly malignant brain tumour, with no evidence of toxicity or side effects, and some long-term survivors.[26][27][28] Other safety trials have used HSV1716 to treat patients with melanoma and squamous-cell carcinoma of head and neck.[29][30] Since then other studies have shown that the outer coating of HSV1716 variants can be targeted to specific types of cancer cells,[31] and can be used to deliver a variety of additional genes into cancer cells, such as genes to split a harmless prodrug inside cancer cells to release toxic chemotherapy,[32] or genes which command infected cancer cells to concentrate protein tagged with radioactive iodine, so that individual cancer cells are killed by micro-dose radiation as well as by virus-induced cell lysis.[33]

Other oncolytic viruses based on HSV have also been developed and are in clinical trials, most notably OncoVex GM-CSF, developed by Amgen, which has successfully completed a pivotal Phase III trial for advanced melanoma. This study met its primary endpoint (durable response rate) with a very high degree of statistical significance in March 2013, the first positive phase 3 study for an oncolytic virus in the western world.[citation needed]

Oncorine (H101)

The first oncolytic virus to be approved by a regulatory agency was a genetically modified adenovirus named H101 by Shanghai Sunway Biotech. It gained regulatory approval in 2005 from China's State Food and Drug Administration (SFDA) for the treatment of head and neck cancer.[13][34] Sunway's H101 and the very similar Onyx-15 have been engineered to remove a viral defense mechanism that interacts with a normal human gene p53, which is very frequently dysregulated in cancer cells.[34] Despite the promises of early in vivo lab work, these viruses do not specifically infect cancer cells, but they still kill cancer cells preferentially.[34] While overall survival rates are not known, short-term response rates are approximately doubled for H101 plus chemotherapy when compared to chemotherapy alone.[34] It appears to work best when injected directly into a tumour, and when any resulting fever is not suppressed.[34] Systemic therapy (such as through infusion through an intravenous line) is desirable for treating metastatic disease.[35] It is now marketed under the brand name Oncorine.[36]

Mechanisms of action

Direct oncolysis

Direct oncolysis, the cell killing effect produced by viral infection of cancer cells, was the original concept of oncolytic viruses.[1][37] By specific infection of a tumour cell, the virus multiplies within it until it causes cell lysis, releasing a second generation of virus to then infect surrounding cells.[3]

Immunotherapy

With advances in cancer immunotherapy such as immune checkpoint inhibitors, increased interest was given to the prospect of oncolytic viruses as immunotherapies. There are two main considerations of the interaction between oncolytic viruses and the immune system.

Immunity as an obstacle

A major obstacle to the success of oncolytic viruses is the patient immune system which naturally attempts to deactivate any virus. This can be a particular problem for intravenous injection, where the virus must first survive interactions with the blood complement and neutralising antibodies.[38] It has been shown that immunosuppression by chemotherapy and inhibition of the complement system can enhance oncolytic virus therapy.[39][40][41]

Pre-existing immunity can be partly avoided by using viruses that are not common human pathogens. However, this does not avoid subsequent antibody generation. However, some studies have shown that pre-immunity to oncolytic viruses doesn't cause a significant reduction in efficacy.[42]

Alternatively, the viral vector can be coated with a polymer such as polyethylene glycol, shielding it from antibodies, but this also prevents viral coat proteins adhering to host cells.[43]

Another way to help oncolytic viruses reach cancer growths after intravenous injection, is to hide them inside macrophages (a type of white blood cell). Macrophages automatically migrate to areas of tissue destruction, especially where oxygen levels are low, characteristic of cancer growths, and have been used successfully to deliver oncolytic viruses to prostate cancer in animals.[44]

Immunity as an ally

Although it poses a hurdle by inactivating viruses, the patient's immune system can also act as an ally against tumors; infection attracts the attention of the immune system to the tumour and may help to generate useful and long-lasting antitumor immunity.[45][46] This essentially produces a personalised Cancer vaccine.

Many cases of spontaneous remission of cancer have been recorded, though not fully understood, they are thought likely to be a result of a sudden immune response or infection.[47] Efforts to induce this phenomenon have used cancer vaccines (derived from cancer cells or selected cancer antigens), or direct treatment with immune-stimulating factors on skin cancers.[48] Some oncolytic viruses are very immunogenic and may by infection of the tumour, elicit an anti-tumor immune response, especially viruses delivering cytokines or other immune stimulating factors.[49]

Oncolytic behaviour of wild-type viruses

Vesicular stomatitis virus

Vesicular stomatitis virus (VSV) is a rhabdovirus, consisting of 5 genes encoded by a negative sense, single-stranded RNA genome. In nature, VSV infects insects as well as livestock, where it causes a relatively localized and non-fatal illness. The low pathogenicity of this virus is due in large part to its sensitivity to interferons, a class of proteins that are released into the tissues and bloodstream during infection. These molecules activate genetic anti-viral defence programs that protect cells from infection and prevent spread of the virus. However, in 2000, Stojdl, Lichty et al.[50] demonstrated that defects in these pathways render cancer cells unresponsive to the protective effects of interferons and therefore highly sensitive to infection with VSV. Since VSV undergoes a rapid cytolytic replication cycle, infection leads to death of the malignant cell and roughly a 1000-fold amplification of virus within 24h. VSV is therefore highly suitable for therapeutic application, and several groups have gone on to show that systemically administered VSV can be delivered to a tumour site, where it replicates and induces disease regression, often leading to durable cures.[51][52][53][54] Attenuation of the virus by engineering a deletion of Met-51 of the matrix protein ablates virtually all infection of normal tissues, while replication in tumour cells is unaffected.[51]

Recent research has shown that this virus has the potential to cure brain tumours, thanks to its oncolytic properties.[55]

Poliovirus

Main article: PVSRIPO

Poliovirus is a natural neuropathogen, making it the obvious choice for selective replication in tumours derived from neuronal cells. Poliovirus has a plus-strand RNA genome, the translation of which depends on a tissue-specific internal ribosome entry site (IRES) within the 5' untranslated region of the viral genome, which is active in cells of neuronal origin and allows translation of the viral genome without a 5' cap. Gromeier et al. (2000)[56] replaced the normal poliovirus IRES with a rhinovirus IRES, altering tissue specificity. The resulting PV1(RIPO) virus was able to selectively destroy malignant glioma cells, while leaving normal neuronal cells untouched.[57]

Reovirus

Reoviruses, an acronym for respiratory enteric orphan virus, generally infect mammalian respiratory and bowel systems. Most people have been exposed to reovirus by adulthood; however, the infection does not typically produce symptoms. The link to the reovirus' oncolytic ability was established after it was discovered to reproduce well in various cancer cell lines and lyses these cells.[58]

Reolysin is a formulation of reovirus that is currently in clinical trials for the treatment of various cancers.[59]

Senecavirus

Senecavirus, also known as Seneca Valley Virus, is a naturally occurring wild-type oncolytic picornavirus discovered in 2001 as a tissue culture contaminate at Genetic Therapy, Inc. The initial isolate, SVV-001, is being developed as an anti-cancer therapeutic by Neotropix, Inc. under the name NTX-010 for cancers with neuroendocrine features including small cell lung cancer and a variety of pediatric solid tumours.

RIGVIR

Main article: RIGVIR

In the 1960s, a group of scientists in Latvia led by Dr. Aina Muceniece studied oncolytic activity of ECHO viruses, but in 1968 a clinical trial of 5 ECHO enterovirus strains began (in trials participated stage-IV cancer patients volunteers). Scientists decided to continue researching ECHO-7 strain of ECHO virus (later called RIGVIR), because it showed the most pronounced oncolytic properties. III-phase trials started in 1988 with the aim to compare effect of RIGVIR therapy with results of chemotherapy and radiation therapy. In 2004 RIGVIR was patented and registered in Latvia and since then it has been used in cancer therapy.[19] RIGVIR virus was approved in Georgia in February 2015,[12] but in 2016 it was approved also in Armenia. Recent retrospective study published in Melanoma Research revealed that IB-IIC melanoma patients treated with oncolytic virus RIGVIR were 4.39–6.57-fold lower mortality than those, who according to melanoma treatment guidelines did not receive virotherapy and were only observed.[60] In 2015 Rigvir was included into the Latvian National guidelines for treatment of skin cancer and melanoma, developed by the Riga Eastern Clinical University Hospital Task Force.[61] In July 2016 new positive results were published in APMIS journal about RIGVIR efficacy in treatment of lung cancer and histiocytic sarcoma.[62]

Semliki Forest virus

Semliki Forest virus (SFV) is a virus that naturally infects cells of the central nervous system and causes encephalitis. A genetically engineered form has been pre-clinically tested as an oncolytic virus against the severe brain tumour type glioblastoma. The SFV was genetically modified with microRNA target sequences so that it only replicated in brain tumour cells and not in normal brain cells. The modified virus reduced tumour growth and prolonged survival of mice with brain tumours.[63] The modified virus was also found to efficiently kill human glioblastoma tumour cell lines.[63]

Other

The maraba virus, first identified in Brazilian sandflies, is being tested clinically.[64][65]

Engineering oncolytic viruses

Directed evolution

An innovative approach of drug development termed "directed evolution" involves the creation of new viral variants or serotypes specifically directed against tumour cells via rounds of directed selection using large populations of randomly generated recombinant precursor viruses. The increased biodiversity produced by the initial homologous recombination step provides a large random pool of viral candidates which can then be passed through a series of selection steps designed to lead towards a pre-specified outcome (e.g. higher tumor specific activity) without requiring any previous knowledge of the resultant viral mechanisms that are responsible for that outcome. The pool of resultant oncolytic viruses can then be further screened in pre-clinical models to select an oncolytic virus with the desired therapeutic characteristics.[66]

Directed evolution was applied on human adenovirus, one of many viruses that are being developed as oncolytic agents, to create a highly selective and yet potent oncolytic vaccine. As a result of this process, ColoAd1 (a novel chimeric member of the group B adenoviruses) was generated. This hybrid of adenovirus serotypes Ad11p and Ad3 shows much higher potency and tumour selectivity than the control viruses (including Ad5, Ad11p and Ad3) and was confirmed to generate approximately two logs more viral progeny on freshly isolated human colon tumour tissue than on matching normal tissue.[66]

Attenuation

Attenuation involves deleting viral genes, or gene regions, to eliminate viral functions that are expendable in tumour cells, but not in normal cells, thus making the virus safer and more tumour-specific. Cancer cells and virus-infected cells have similar alterations in their cell signalling pathways, particularly those that govern progression through the cell cycle.[67] A viral gene whose function is to alter a pathway is dispensable in cells where the pathway is defective, but not in cells where the pathway is active.

The enzymes thymidine kinase and ribonucleotide reductase in cells are responsible for DNA synthesis and are only expressed in cells which are actively replicating.[68] These enzymes also exist in the genomes of certain viruses (E.g. HSV, vaccinia) and allow viral replication in quiescent(non-replicating) cells,[69] so if they are inactivated by mutation the virus will only be able to replicate in proliferating cells, such as cancer cells.

Tumour targeting

There are two main approaches for generating tumour selectivity: transductional and non-transductional targeting.[citation needed]

  • Transductional targeting involves modifying the viral coat proteins to target tumour cells while reducing entry to non-tumour cells. This approach to tumour selectivity has mainly focused on adenoviruses and HSV-1, although it is entirely viable with other viruses.[citation needed]
  • Non-transductional targeting involves altering the genome of the virus so it can only replicate in cancer cells, most frequently as part of the attenuation of the virus.[citation needed]
    • Transcription targeting can also be used, where critical parts of the viral genome are placed under the control of a tumour-specific promoter. A suitable promoter should be active in the tumour but inactive in the majority of normal tissue, particularly the liver, which is the organ that is most exposed to blood born viruses. Many such promoters have been identified and studied for the treatment of a range of cancers.[citation needed]
    • Similarly, viral replication can be finely tuned with the use of microRNAs (miRNA) artificial target sites or miRNA response elements (MREs). Differential expression of miRNAs between healthy tissues and tumors permit to engineer oncolytic viruses detargeted from certain tissues of interest while allowing its replication in the tumor cells.

Double targeting with both transductional and non-transductional targeting methods is more effective than any one form of targeting alone.[70]

Further information: Oncolytic adenovirus

Reporter genes

 
Viral luciferase expression in a mouse tumour

Both in the laboratory and in the clinic it is useful to have a simple means of identifying cells infected by the experimental virus. This can be done by equipping the virus with 'reporter genes' not normally present in viral genomes, which encode easily identifiable protein markers. One example of such proteins is GFP (Green fluorescent protein) which, when present in infected cells, will cause a fluorescent green light to be emitted when stimulated by blue light.[71][72] An advantage of this method is that it can be used on live cells and in patients with superficial infected lesions, it enables rapid non-invasive confirmation of viral infection.[73] Another example of a visual marker useful in living cells is luciferase, an enzyme from the firefly which in the presence of luciferin, emits light detectable by specialized cameras.[71]

 
Vaccinia virus infected cells expressing beta-glucuronidase (blue colour)

The E. coli enzymes beta-glucuronidase and beta-galactosidase can also be encoded by some viruses. These enzymes, in the presence of certain substrates, can produce intense colored compounds useful for visualizing infected cells and also for quantifying gene expression.

Modifications to improve oncolytic activity

Oncolytic viruses can be used against cancers in ways that are additional to lysis of infected cells.

Suicide genes

Viruses can be used as vectors for delivery of suicide genes, encoding enzymes that can metabolise a separately administered non-toxic pro-drug into a potent cytotoxin, which can diffuse to and kill neighbouring cells. One herpes simplex virus, encoding a thymidine kinase suicide gene, has progressed to phase III clinical trials. The herpes simplex virus thymidine kinase phosphorylates the pro-drug, ganciclovir, which is then incorporated into DNA, blocking DNA synthesis.[74] The tumour selectivity of oncolytic viruses ensures that the suicide genes are only expressed in cancer cells, however a 'bystander effect' on surrounding tumour cells has been described with several suicide gene systems.[75]

Suppression of angiogenesis

Angiogenesis (blood vessel formation) is an essential part of the formation of large tumour masses. Angiogenesis can be inhibited by the expression of several genes, which can be delivered to cancer cells in viral vectors, resulting in suppression of angiogenesis, and oxygen starvation in the tumour. The infection of cells with viruses containing the genes for angiostatin and endostatin synthesis inhibited tumour growth in mice. Enhanced antitumour activities have been demonstrated in a recombinant vaccinia virus encoding anti-angiogenic therapeutic antibody and with an HSV1716 variant expressing an inhibitor of angiogenesis.[76][77]

Radioiodine

 
Adenoviral NIS gene expression in a mouse tumour (Located at the crosshairs) following intravenous delivery of virus (Left) compared to an uninfected control mouse (Right)

Addition of the sodium-iodide symporter (NIS) gene to the viral genome causes infected tumour cells to express NIS and accumulate iodine. When combined with radioiodine therapy it allows local radiotherapy of the tumour, as used to treat thyroid cancer. The radioiodine can also be used to visualise viral replication within the body by the use of a gamma camera.[71] This approach has been used successfully preclinically with adenovirus, measles virus and vaccinia virus.[78][79][80]

Approved therapeutic agents

Clinical research

In 2014-2016 period a number of clinical trials were initiated for a wide range of oncolytic virus products, reflecting the ongoing clinical development of this class of therapy.[86]

AgentIndicationPhaseStatusRouteNotesRef
Ad5-yCD/mutTKSR39rep-hIL12 Prostate carcinoma I Recruiting Intraprostatic As single agent NCT02555397
Cavatak Bladder carcinoma I Recruiting Intravesical Optionally combined with low-dose mitomycin C NCT02316171
  Melanoma I Recruiting Intratumoral Combined with ipilimumab NCT02307149
          Combined with pembrolizumab NCT02565992
CG0070 Bladder carcinoma II No longer available Intravesical As single agent NCT02143804
      Recruiting Intravesical As single agent NCT02365818
DNX-2401 Brain tumors I Recruiting Intratumoral Combined with IFNγ NCT02197169
G207 Brain tumors I Not yet recruiting Intratumoral Optionally combined with radiation therapy NCT02457845
GL-ONC1 Ovarian cancer Ib Recruiting Intraperitoneal As single agent NCT02759588
HF10 Melanoma II Recruiting Intratumoral Combined with ipilimumab NCT02272855
  Solid tumors I Recruiting Intratumoral As single agent NCT02428036
Imlygic® Hepatocellular carcinoma I Not yet recruiting Intratumoral As single agent NCT02509507
  Melanoma n.a. Enrolling by invitation Intratumoral As single agent NCT02173171
    II Recruiting Intratumoral As single agent NCT02366195
          Combined with surgery NCT02211131
    III Active, not recruiting Intratumoral Combined with pembrolizumab NCT02263508
      Available Intratumoral As single agent NCT02147951
            NCT02297529
  Soft tissue sarcoma I/II Recruiting Intratumoral Combined with radiotherapy NCT02453191
JX-594 Hepatocellular carcinoma III Not yet recruiting Intratumoral Combined with sorafenib NCT02562755
MG1-MA3 Solid tumors I/II Recruiting Intravenous Combined with a MAGEA3-encoding adenovirus NCT02285816
MV-NIS Gynecological tumors II Recruiting Intraperitoneal As single agent NCT02364713
  Multiple myeloma II Recruiting Intravenous Combined with cyclophosphamide NCT02192775
OBP-301 Solid tumors I Not yet recruiting Intratumoral As single agent NCT02293850
Reolysin® Brain tumors I Recruiting Intravenous Combined with GM-CSF s.c. NCT02444546
  Multiple myeloma I Recruiting Intravenous Combined with dexamethasone plus a proteasomal inhibitor NCT02101944
            NCT02514382
Toca 511 Brain tumors II/III Not yet recruiting Intratumoral Combined with 5-FC and standard chemotherapy NCT02414165
  Solid tumors I/II Recruiting Intratumoral Intravenous Combined with 5-FC NCT02576665
             

Abbreviations: 5-FC, 5-fluorocytosine; GM-CSF, granulocyte macrophage colony-stimulating factor; IFNγ, interferon γ; MAGEA3, melanoma antigen family A3; s.c.,sub cutem.*initiated between 2014, March 1 and 2015, October 31.

Approved somewhere

  • Talimogene laherparepvec was approved by the US FDA in 2015, with the brand name Imlygic, for the treatment of melanoma in patients with inoperable tumors.[82] In Jan 2016 it was approved in Europe for some inoperable melanoma.[87]
  • Oncorine, by Shanghai Sunway Biotech, was approved in China for Head and neck cancer in 2005.[88] It is based on the adenovirus H101.
  • RIGVIR, approved for melanoma treatment in Latvia (2004), Georgia (2015) and Armenia (2016) for melanoma treatment.

Started phase III

  • Reolysin, by Oncolytics Biotech, is in phase III for head and neck cancer.[89] An interim data release showed that this phase III had already obtained statistically significant tumor shrinkage in patients at their 6-week scan,[90] although the trial will not be complete until the overall survival data matures. Encouraging early results in colorectal cancer.[91][92] In total there are 31 clinical studies either completed or ongoing, including many testing Reolysin alongside standard chemotherapies in a variety of solid cancers.[93]

Started phase II

  • JX-594, by Jennerex, is currently in phase II for hepatocellular carcinoma.[94] JX-594 is a thymidine kinase-deleted Vaccinia virus plus GM-CSF.[95][96]
  • Seneca Valley virus (NTX-010) and (SVV-001), oncolytic picornavirus, is in phase II for small cell lung cancer and neuroblastoma.[9][88][97][98]
  • ColoAd1 was developed by Psioxus Therapeutics Ltd using the process of directed evolution. ColoAd1 has successfully completed recruitment in a Phase I clinical trials of ColoAd1.[citation needed] The trial involved recruiting patients with metastatic solid tumours where no standard treatment options were applicable. Samples from these patients showed evidence of virus replication within tumour sites after intravenous delivery. The second phase of the ColoAd1 study is planned to commence in 2014 and will examine efficacy in patients with metastatic colorectal cancer. Unlike many other oncolytic viruses, ColoAd1 can be administered by intravenous injection rather than requiring intra-tumoral injection. A second trial is comparing the efficacy of the intravenous approach versus direct intra-tumoural injection to assess the most effective method of delivering ColoAd1 to cancer patients (see the EU Clinical Trials Register for further details). A third trial is examining the intra-peritoneal route of delivery for women with late stage ovarian cancer.
  • Cavatak[99][100] is a coxsackie virus which is in phase II clinical trials for the treatment of malignant melanoma.[101]

Started phase I

  • SEPREHVIR (HSV-1716), by Virttu Biologics,[102] completed phase I in glioblastoma, in squamous cell carcinoma of head and neck, and in melanoma. Ongoing phase I dose escalation study of intratumoral HSV-1716 in pediatric/young adult patients with non–central nervous system solid tumours and a new phase I/IIa study in mesothelioma commenced in 2012.[103][104]
  • CGTG-102 (Ad5/3-D24-GMCSF), by Oncos Therapeutics,[105] while in phase I was already used to treat 200 advanced cancer patients in the company's Advanced Therapy Access Program.[106]
  • GL-ONC1, by Genelux, is in phase Ib administered intravenously for solid tumours.[107] Additional trials are ongoing utilising alternative methods of administration including intrapleural administration for patients with malignant pleural effusion,[108] intraperitoneal injection for patients with advanced peritoneal carcinomatosis,[109] intraperitoneal injection for recurrent ovarian cancer,[110] and intravenous injection in combination therapy in head and neck cancers.[111]
  • MV-NIS, an engineered measles virus has shown to be effective in targeted destruction of myeloma plasma cells. Radioactive Iodine imaging provides a novel technique for NIS gene expression monitoring.[112]
  • DNX-2401 is an oncolytic adenovirus with US Orphan drug status for glioma.[113]
  • ONCOS-102 is an engineered human serotype 5/3 adenovirus coding for human GM-CSF optimized to induce systemic anti-tumor T cell response in cancer patients. It has completed a phase I trial and is starting another for malignant pleural mesothelioma (MPM).[114]

Oncolytic viruses in conjunction with existing cancer therapies

It is in conjunction with conventional cancer therapies that oncolytic viruses have often showed the most promise, since combined therapies operate synergistically with no apparent negative effects.[115]

Clinical trials

Onyx-015 underwent trials in conjunction with chemotherapy before it was abandoned in the early 2000s. The combined treatment gave a greater response than either treatment alone, but the results were not entirely conclusive.[116] Hepres simplex virus, adenovirus, reovirus and murine leukemia virus are also undergoing clinical trials as a part of combination therapies.[117]

Pre-clinical research

Chen et al. (2001)[118] used CV706, a prostate-specific adenovirus, in conjunction with radiotherapy on prostate cancer in mice. The combined treatment resulted in a synergistic increase in cell death, as well as a significant increase in viral burst size (the number of virus particles released from each cell lysis). No alteration in viral specificity was observed.

SEPREHVIR (HSV-1716) has also shown synergy in pre-clinical research when used in combination with several cancer chemotherapies.[119][120]

The anti-angiogenesis drug Bevacizumab (anti-VEGF antibody) has been shown to reduce the inflammatory response to oncolytic HSV and improve virotherapy in mice.[121]

In fiction

In science fiction, the concept of an oncolytic virus was first introduced to the public in Jack Williamson's novel Dragon's Island, published in 1951, although Williamson's imaginary virus was based on a bacteriophage rather than a mammalian virus.[122] Dragon's Island is also known for being the source of the term "genetic engineering".[123]

The plot of the Hollywood film I Am Legend is based on the premise that a worldwide epidemic was caused by a viral cure for cancer.[citation needed]

See also

References

Further reading

  • Harrington, Vile, Pandha (2008). Viral Therapy of Cancer. Hoboken, N.J.: Wiley. ISBN 0470019220.
  • Thorne, Kirn, Liu (2011). Oncolytic Viruses: Methods and Protocols (Methods in Molecular Biology). New York: Humana Press. ISBN 1617793396.
  • Sinkovics (2005). Viral therapy of human cancers. New York: Dekker. ISBN 0824759133.

External links

Therapeutic Substance(s): 
Therapeutic intervention: 
Disease(s): 

Ozone Therapy

field_vote: 

Ozone Therapy Information, Ozone Therapy Articles, and Ozone Therapy Studies

Ozone Therapy Summary: (from http://www.oxygenhealingtherapies.com/ozone_therapy.html)
Ozone Therapy is a medical therapy that has been used worldwide for over 50 years with dramatic success and safety. In North America Ozone Therapy has not yet been fully recognized by the medical authorities, however if you review our ever growing list of Ozone Doctors, you will see that it is being adopted more and more by formally 'traditional' medical practitioners. It is clear that Ozone Therapy works, and it is becoming one of the most useful tools in medical clinics across America and around the World. (See "A Review of Ozone Therapy Applications" to learn how ozone is being administered). If you are completely new to Ozone and are wondering what all the fuss is about, read our new section Ozone Therapy Basics and then come back to these articles.

What does it do? To breifly summarize, ozone accomplishes these very important tasks in your body:

1/ Ozone is AntiAging (some of those AntiAging effects can be attributed to the following list of actions...)
2/ Ozone Increases Oxygenation of your Cells (it has been proven that cancer and disease grow in poorly oxygenated tissues in your body).
3/ Ozone Modulcates your Immune System (for those with a weakened immune system, Ozone will boost the immune system. For those with Auto-Immune Disorders, Ozone will modulate the immune system to help to stop it from attacking healthy human cells.)
4/ Ozone Increases Energy Production in your Cells (your cells need energy to be healthy; low energy levels mean that you and your cells will not be healthy and will age)
5/ Ozone Increases the Activity of your "Anti-Oxidant Enzyme Systems". This means ozone will reduce the oxidation levels of your body.
6/ Ozone Reduces the level of acidity of your body (never mind the Alkaline Water...use Ozone!)
7/ Ozone kills Bacteria, Viruses (and virtually all other disease causing organisms) on contact
8/ Ozone Kills Cancer cells on contact


The IOA - The International Ozone Association holds International Ozone Congresses every two years in various locations around the world. AEPROMO - The Spanish Association of Medical Professionals in Ozone Therapy also holds World Ozone Congresses every two years. The recent Ozone Congress held June 2012 in Madrid Spain attracted Ozone Therapy Doctors from 25 countries around the world! Countries such as Brazil, Germany, Russia, Spain, Italy, Turkey, Austria, and even the USA all have their own Ozone Thearpy Associations which hold yearly conventions (Congresses) where physicians from around the world attend to present their new findings, new procedures, and results of new studies. In 2009 there was a very public announcement in Toronto Canada, an announcement that shook the world when everyday "allopathic" medical doctors openly announced that Ozone not only can ozone be used to successfully treat herniated discs, but the studies indicate that Ozone Therapy works far better than traditional surgery!

The word is out and the door is open. Whether you are already knowledgeable about Ozone and know its value in medicine, or whether you are a skeptic, you will enjoy this site on Ozone Therapy. Review the articles posted here, learn about how ozone works, take a course from one of our many Ozone Courses. Learn.

Read the articles in this section to find out how Ozone Therapy may help you!

Psorinum, the anti cancer miracle from India.

field_vote: 
At the ASCO(American Society of Clinical Oncology) congress in Chicago from June 4th to 8th 2010, the world's most prestigious congress of clinical oncology with 30 to 35,000 participants, was published on the poster section a rather sensational result in the treatment of non-small cell lung cancer with an increase of five year survival from an expected <1% to 44%!!
There are also extremely good results in the treatment of gastro.intestinal cancers.
 
by Aradeep Chtterjee et al from Calcutta, India.
Although, great advances have been made in the treatment of some forms of cancer and new advances in surgery, radiotherapy, and chemotherapy leading to an increase in cure rates have been achieved, such interventions are often too much expensive and beyond the reach of many cancer patients of the developing as well as of the developed countries. In developing countries, majority of the cancer patients have inadequate access to the mainstream cancer treatments due to lack of proper medical infrastructures, skills, and above all limited financial resources.
Some types of cancer (i.e., liver, gall bladder, pancreatic, and stomach) are still associated with poor prognosis to conventional cancer treatments.
 
Side effects of the chemotherapy and radiation therapy are also intolerable to many cancer patients. In most of the situations, elderly cancer patients cannot be provided with conventional cancer treatments because of old age-related problems . As a result, alternative cancer treatments have become an important feature of oncology regardless of geographic region and they appear to exist in greater abundance through out the world. Many alternative cancer therapeutic modalities are now being practiced in India, and one of them which has gained significant popularity is called Psorinum Therapy .
 
The investigational anticancer drug used in this alternative cancer therapy is “Psorinum” which is derived from the sphere of homeopathy. The supportive treatments of Psorinum Therapy are adopted both from the spheres of allopathy and homeopathy. Psorinum is an alcoholic extract of the scabies, slough, and pus cells. According to the pre-clinical data, “Psorinum-6x” (“x” stands for decimal potency of homeopathy) activates different immune effector cells (e.g., T cells, and accessory cells like, macrophages, dendritic cells, and natural killer cells) which can trigger a complex antitumor immune response . In a rat model study, daily oral administration of Psorinum 6x at doses up to 0.5 ml/Kg body weight/day for 2 weeks resulted in no adverse side effect  Published retrospective and prospective studies also support the efficacy of Psorinum Therapy in treating patients with various malignancies.
 
In an observational, open level and single arm study on158 patients with histologically confirmed stomach, gall bladder, liver and pancreatic cancer, complete tumor response occurred in 28 (17.72%) cases and partial tumor response occurred in 56 (35.44%) of cases The participants' eligibility criteria included histopathology/cytopathology confirmation of malignancy, inoperable tumor, and no prior chemotherapy or radiation therapy. The primary outcome measures of the study were (i) to assess the radiological tumor response (ii) to find out how many participants survived at least 1 year, 2 years, 3 years, 4 years and finally 5 years after the beginning of the study considering each type of cancer. Psorinum-6x was administered orally to all the participants up to 0.02ml/Kg body weight as a single dose in empty stomach per day for 2 years along with allopathic and homeopathic supportive cares. There were 42 stomach cancers, 40 gall bladder cancers, 44 pancreatic cancers and 32 liver cancers included in the final analysis of the study. 
Some other homeopathic medicines were also used for supportive care:
Table 1
Details of the frequently used homeopathic medicines for the purpose of the supportive cares.
NameOriginDosingPowerUsed to control ailments
(1) Chelidonium majus Herb-Chelidonium majus Up to 0.04 ml/Kg body weight/day orally Mother tincture (1) Abnormal liver functions
 (2) Dysponea
(2) Carduus marianus Herb-Carduus marianus Up to 0.04 ml/Kg body weight/day orally Mother tincture (1) Abnormal liver function
 (2) Cholestasis
(3) Baryta carbonica Barium carbonate Up to 0.02 ml/Kg body weight/day orally 200c (1) Anaemia
 (2) Cancer-related pain
(4) Conium maculatum Herb-Conium maculatum Up to 0.02 ml/Kg body weight/day orally 200c (1)Heart troubles
(2) Abnormal blood pressure
(5) Carbo animalis Animal charcoal Up to 0.02 ml/Kg body weight/day orally 200c (1) Cough
(2) Constipation
(6) Bryonia alba Herb-Bryonia alba Up to 0.02 ml/Kg body weight/day orally 200c (1) Dysponea
(2) Cancer-related pain
(7) Medorrhinum Gonorrhoeal cocci Up to 0.02 ml/Kg body weight/day orally 200c (1) Abnormal blood sugar
(2) Cancer-related pain
(8) Thuja occidentalis Herb-Thuja occidentalis Up to 0.02 ml/Kg body weight/day orally Mother tincture (1) Abdominal distension
(2) Electrolytic imbalance
(9) Cholesterinum Cholesterine Up to 0.02 ml/Kg body weight/day orally 200c (1) Abnormal liver function
(2) Cholestasis
(10) Lycopodium clavatum Herb-Lycopodium clavatum Up to 0.02 ml/Kg body weight/day orally 200c (1) Abdominal distension
(2) Cancer-related pain
 
 (5.95%) participants were dropped out from the study as they opted for conventional cancer treatments, among them 4 of stomach, 2 of gall bladder, 3 of pancreatic, and 1 of liver cancers.  Among the 158 participants, 84 (53.16%) were male and 74 (46.84%) were female. According to the AJCC TNM staging system, 39 (24.68%) were diagnosed at stage-III, and 112 (70.89%) were diagnosed at stage-IV. The participants' Karnofsky status was between 40–70%, and Eastern Cooperative Oncology Group (ECOG) status was between 2-3. Among the 39 participants (24.68%) who were diagnosed at stage-III, 13 (33.33%) had complete response and 16 (41.03%) had radiological partial response. Among the 112 (70.89%) participants who were diagnosed at stage-IV, 12 (10.71%) had radiological complete response and 38 (33.93%) had radiological partial response
 
In this study, no adverse side effects were observed from the drug Psorinum. However, very few patients reported to have mild oral irritation and skin itching which were successfully controlled by the supportive cares. Psorinum Therapy was also effective in improving the disease symptoms and the quality of life of the participants. At least 60% participants of stage-III and at least 45% participants of stage-IV reported that the therapy was effective in reducing their cancer-related pain, cough, dysponea, nausea and vomiting, fatigue, constipation and improving appetite, and weakness. These were also confirmed after examining the participants clinically. Improvements were also observed in the lab investigations like Complete Blood Count (CBC), Liver Function Test (LFT), Kidney function test, AFP level, and CA 19.9. These lab investigations were done as a part of their routine clinical check ups. Among the 158 participants, 98 (62.03%) were aged 65 years or more. Better outcomes were observed among the participants below 65 years of age than the participants who were over the age of 65. The outcomes did not vary significantly while considering gender.
Table 2
TNM Staging, partial and complete tumor response in each cancer type.
Primary cancer typesNo. of participantsTNM Staging of the participantsNo. of patients: Complete tumor response occurredNo. of patients: Partial tumor response occurred
Diagnosed at stage-II and stage-IIIDiagnosed at stage-IV
Stomach 42 11 31 6 (14.29%) 16 (38.1%)
G. Bladder 40 13 27 7 (17.5%) 17 (42.5%)
Pancreas 44 9 35 8 (18.18%) 13 (29.55%)
Liver 32 13 19 7 (21.87%) 10 (31.25%)
Table 3
Survival outcomes in each cancer type.
Primary organ affectedNo. of PatientsMaleFemaleSurvived at least 1 yearSurvived at least 2 yearsSurvived at least 3 yearsSurvived at least 4 yearsSurvived at least 5 years
Stomach 42 22 20 34 24 21 20 16 (38.1%)
G. Bladder 40 21 19 32 25 20 18 15 (37.5%)
Pancreas 44 24 20 34 28 27 21 17 (38.64%)
Liver 32 17 15 26 22 19 17 14 (43.75%)
 
Discussion
The cumulative 5-year survival was 39.24% for patients who received Psorinum treatment, compared with an estimated 5-year survival of 23% for stomach cancer, 10% for liver cancer, <4% for pancreatic cancer and <15% for gall bladder cancer for patients taking conventional therapies. 28 patients (17.72%) had a complete recovery from their cancer in this study.
 
Psorinum in the treatment of Non Small Cell Lung Cancer(NSCLC)
In another phase II, open-level, single arm, and single stage  study, also performed by Dr Chatterje et al, 95 participants were included with NSCLC.
According to the AJCC TNM staging system, 58 (61.05%) of them diagnosed at stage IV. According to the RECIST criteria, complete tumor
response occurred in 19 (20%) cases and partial tumor response occurred in 28 (29.47%) cases. 82 (86.32%) of them survived at least 1 yr, 70
(73.68%) survived at least 2 yrs, 58 (61.05%) survived at least 3 yrs, 49 (51.58%) survived at least 4 yrs, and 42 (44.21%) of them survived at
least 5 yrs. These participants did not receive chemotherapy, radiation therapy, or any other investigational cancer treatments. Participants
reported no side effects from the drug psorinum.
 
Regarding pancreatic cancer:
44 patients participated in the study with Psorinum D6, 0,02 ml per kg body weight in the morning on empty stomach. Survival after first year 34,
after 2 years 28, after 3 years 27, after 4 years 21, and after 5 years 17 of the patients were still alive, equal to a 5-year survival of 39% - Probably the highest ever recorded 5 yearr survival on Pancreatic  Cancer published so far in medicine history!!
These results were examined by a very critical an independent expert commission at the National Cancer Institute in Bethesda, near Washington DC, USA, who has accepted the results, so that Dr. Chatterjee was able to present the results at the ASCO conference. There are plans to make more research on Psorinum on the famous MD Andersson Cancer Institute in Houston,  Texas, USA
The treatment is suitable for many more cancer types, but research has so far been focused on the more difficult cancers.
Dr Mikael Nordfors has been treating a few patients in Europe with Psorinum, with similar results as in India. He also combines psorinum treatment with GcMAF, LDN, Cancer psychotherapy and other immune strengthening treatments
Some of these case stories are published below.
 
 
Therapeutic Substance(s): 
Therapeutic intervention: 

Todoxin, the immune stimulant from Serbia

field_vote: 

From http://torexin.com/Cancer.html, http://torexin.com/dah_studija.html and http://torexin.com/hiv_aids.html


Issue 11/1998 of 08/06/1998
Introductory remark

In regard with so called "alternative" medicaments there has been a discussion going on for some time about a preparation called "TODoXIN". There is too little information on the effectiveness of this preparation, but the articles are circulating on the topic of "the medicine: 'TODoXIN'" expressing excitement or rejection. As far as we know, there are no underpinned contributions in which all the knowledge would be critically worked out and summarized. By the following detailed article we wish to fill this gap.

Introduction

"TODoXIN" is a herbal remedy which has been applied on over 7,000 patients in the cases of different (oncogen) viruses and against HIV-infection effects for 10 years. It was developed by Dr. Todor Jovanovic, a physician born in Vrani Do, Kosovo, in 1935. Dr. Jovanovic studied medicine in Belgrade and finished his specialization in Allergology. After the graduation he carried out research in the UN Research Centre for Nuclear Medicine and in military research centre in Vinca, near Belgrade. The main field of the research was search for histocompatible materials for implantats. Another field of intensive work was the research and monitoring of immunostimulating effects of plant extracts.

In 1987, Dr. Jovanovic applied for a patent on TODoXIN recipe. After that, he made an effort to get the support of experts and institutions in the country and abroad for his projects. There were, among others, the president of Serbian Academy of Science and Art, Dusan Kanazir, Luk Montagnier, the man who discovered HIV, as well as the leader of the special program of WHO for AIDS, Jonathan Man.

Because of the sparse data, no one showed interest for that project, except for the leader of a research group from Austria. With the Austrian partners in the research, Dr. Jovanovic signed a long-term contract on cooperation in 1988. The goal of the cooperation was to test the remedy on the international scale, galenic development and later, submission of the appropriate study results, obtaining the international approval and production.

After it has been proved toxicologically safe in 1988, the Austrian team, in collaboration with the Karolinska Institute for Immunology in Stockholm, in 1988-89, succeeded in showing the immunostimulating properties of TODoXIN in vitro, as well as the development of pharmacodynamic model of effect mechanisms induced on the immuoendocrinal level. That model could have been tested ex vitro and and confirmed in vivo. It was followed by intensive medical observation of its use, in collaboration with some clinical workers and physicians, in a wide spectrum of potential indications for immunostimulating properties of TODoXIN. On the basis of the data obtained by early 1991, the scientists of National Institutes of Health (NIH), in Washington, expressed their readiness to examine TODoXIN in vitro within the "Developmental Therapeutics Program". The studies of HIV culturing proved that cell bearable concentrations of active agents of TODoXIN can inhibit HIV up to 100%.

At the end of 1991 TODoXIN was given the license for production in Yugoslavia under the register number 4684 dd 31/10/88, as a "dietetic product based on honey and medicinal herbs ". The records on HIV- inhibiting capacity of TODoXIN, obtained at NIH, as well as the results of HIV-positive patients treated with TODoXIN since 1988, were not presented until the 10th International Conference on AIDS in Yokohama (1994), because NIH which was late in giving the permission for releasing the data.

On the basis of these data the Austrian research group succeeded in winning over the European virologists and AIDS researchers, prof. Richard Teddar and Dr. Clive Loveday from UCL Medical School of London, to the scientific collaboration. The data jointly won over the years that followed were appraised and designated as “very promising" by members of the British Medical Research Council – MRC and HIV Clinical Trial Centre – prof. A. Brackenridge, prof. D. Jeefries, prof. I. Weller and Dr J. Darbyshire.

On the 11. International AIDS Conference in Vancouver (1996), an official symposium on TODoXIN was held, where the most recent data were presented.

After that, the Department for Retro virology of Royal Free Medical School in London came up with offer to carry out further studies in England under official supervision of pharmaceutical authorities, MRC and one ethical committee. The results of these studies were supposed to support the official request for registration of TODoXIN in the European Union. The study started, after longer preparations, in September 1997, after it had been established that TODoXIN is to be produced in the future by Dr. Jovanovic together with an Austrian partner in the research, within one Austrian firm.

In the course of the study, Dr. Jovanovic decided to accept the offers of English researchers and their American partners to have TODoXIN produced in the USA in the future and to carry out further study over there. In order to present data which were up-to-date in 1998. to American partners, the London study, started in 1997, was interrupted in March 1998, and a new study was started, using the first laboratory samples of American TODoXIN. A separate American study is still about to start this year in California. Therefore, for the precaution sake, no new TODoXIN data were presented in the 12th International AIDS Conference in Geneva.


Composition

TODoXIN is made exclusively of plants and does not contain any synthetic components and preservatives.

Plants or parts of plants which are used for preparation are regularly tested for toxins which naturally occur, and for the presence of toxically substances used in agriculture (DDT, Lindan, Dieldrin, Endrin, Hexachlorbenzol, heavy metals, nitrites, nitrates, fungi, aerobic and anaerobic bacteria etc.)

In a joint poster session (abstract PA0340) presented by "TODoXIN Study Group" at 10th International AIDS Conference in Yokohama (1994) to the Department of Immunology of the Karolinska Institute (Sweden) and National Institutes of Health of the USA the composition of TODoXIN was presented in the following way:

"TODoXIN is a novel antiviral and immunostimulating preparation based upon an ion carrier molecule with specific binding affinities and a carrier specific substrate formulation. TODoXIN's formulation is unique in three aspects:

1. It comprises a very broad spectrum of physiologically active, cis-oriented and water soluble carbohydrates, carboxylic acids, vitamins, fat soluble vitamins, coenzymes and enzymes such as Amylases, Phosphates and Catalyses.

2. It contains both agonic and antagonic agents such as Ca and Fe, in physiologically relevant concentrations.

3. It contains a spectrum of minerals in permanent solution."

Micro-nutrients present in TODoXIN are exclusively of plant origin. They are obtained directly from fruits (mainly citrus fruits). Formulation also contains about 20 vol.-% honey.

Herbal active substance is kept in secret by Dr. Jovanovic. At present, there is a patent procedure running on the territory of the Former Yugoslavia. The exact composition, as well as pharmacokinetic data are not available for publication (not even in the editorial office). However, every therapeutic physician who would like to apply TODoXIN can have access to this data.


The up to date experience confirm the following indication:

myelo-proliferative syndrome

osteosarkoma

acute lymphoblast leukemia

acute myeloid leukemia

malignant lymphoma

adenocarcinom

testicular tumor, prostate, breast, rectum, cradle, lungs, skin and all gynecologist cancers.

 

There is hope even in case of very progressive diseases, like in lang metastasis, liver, bones. In many cases when patients were inoperable, because of diffusible infiltration of primary tumor into adjoining tissue and many metastasis even in case of bone decalcification, after TODOXIN therapy, the primary tumor is more clearly differentiated, looses in mass and becomes operable. Metastasis has disappeared, bones have been recalcificated and patients experienced complete remission. This phenomenon is 100 times more frequent than so called spontaneous remission in oncology practice.

However, it is most useful to start TODOXIN therapy as soon as the diagnosis has been established, for the effects are much better if it starts sooner. In progressive stadiums of cancer, a week can sometimes has the same significance as a whole year in different phases of cancer.

HIV/AIDS INFECTION

TODoXIN is in official use since 1963. Over 1300 HIV1 and 2 infected patients have been treated and the results are:

At patients whose virus serum was observed in short intervals, periodical appearance of HIV1 free virus (RNA virus serum) was noticed in the beginning of therapy during first 14 days of the high dose therapy cycles (taking every 2 hours).

 

There comes the increasing of 20 times above the average values and after that the gentle decreasing of virus serum which is on the detection limit (up to 4 log) in period between second and sixth week. Further on the value of virus serum constantly decreases (at detection limit, less than 20c/ml) after two to four cycles of the high dose therapy, that is 12-14 weeks.

After 6-18 months, the number of CD 4 cells increases for 50-150% of basic values and it happens with most patients. The time necessary for reaching and exceed the referent values is proportional to time extend of HIV infection before the therapy.

The significant changes during the therapy initiate the introduction of special forward therapy with corresponding dozes. This therapy deduces the clinical symptoms of viremia to minimum (to less than 2%).

Therapeutic Substance(s): 
Therapeutic intervention: 

Medical Cannabis Compounds

field_vote: 

Cannabis: Food and Medicine

Mark Pedersen quote

 

Cannabis is a food — not a substance, not an illicit drug, not a herb. It is simply a food, and as with all superfoods, it has a myriad of healing properties, according to Mark Pedersen of the eCS Therapies Center, an organization which concentrates on cannabis education.

 

“My life mission is to change the cannabis law throughout our country and the world, and see cannabis treated like any other agricultural crop, the same as spinach or lettuce or any other product,” Pedersen said. “[Cannabis is a] food, it's a superfood, and that's the way it should be.”

 

Pedersen has been a cannabis patient for more than 20 years and intimately involved in trying to change state laws in the United States for the past 10 years. “What I have been about over the last 10 years is I've traveled the country, I've interviewed cannabis patients throughout, and I've interviewed scientists and doctors, as well as different people in different levels of government, all talking about cannabis — and cannabis particularly as medicine,” he said.

 

“Over the course of the last four and a half to five years I have been producing cannabis oil for the chronically and terminally ill while I've been living here in Colorado and of late, that has moved to where I pretty much deal with end-of-life cases, Stage IV cancers and such. I've worked with children as young as the age of 8 months, [as well as] with adults and seniors.”

 

Mark Pedersen

“When we deal with treating illness with prescription drugs we're dealing with poison, plain and simple.”

Mark Pedersen

 

Discovering cannabis therapy

 

A native of Missouri and father of three, Pedersen has his own testimonial on the effectiveness of cannabis as medicine. “At one point in my life I was working 80-plus hours a week,” he said. “I was a certified welder and pipe fitter. I worked in power plants — a heavy-metal worker. I worked with very toxic and noxious things like asbestos and such. I also had a small computer consulting business with about 12 to 13 business clients. And I had a benevolence ministry. I did counseling, both spiritual and financial counseling, as well as a great deal of hospital visitations. That is when I first experienced spending a lot of time with people who were dying. I also had a food pantry, which then grew into a pantry association which covered three counties. This is where my life was. Quite literally, I worked 80-plus hours a week. Then I became ill.

 

“The community where I grew up and later worked in, the principle industry there was lead smelting. The pollution was in our air. It was in the dust that blew in from the roads. It was everywhere in our home. We had our home tested by a consulting firm and found it off the charts for lead, arsenic, and the different byproducts of the lead industry. I had purchased a house in that small community and proceeded to add some rooms to it, opening up the walls and pulling up the carpet, and I exposed my family to 100 years worth of those carcinogens. That really pushed me over the edge.”

 

Pedersen's health declined to the point where he was unable to work, lost his home, cars, careers, and marriage. He also lost his oldest daughter when she was 20 years old. Pedersen noted she had been sick most of her life, probably due to the same types of toxic exposures.

 

“My original diagnosis was severe migraines and fibromyalgia,” Pedersen said. “That's pretty much what it amounted to. My disability happened in 1997, and that's when I rediscovered cannabis in a blip in a fibromyalgia newsgroup — if you remember the newsgroups. I saw that cannabis can be effective in treating fibromyalgia and the pain. I went to a friend of mine and got some poor quality cannabis and started treating myself with it in the best way I knew how which was smoking it. I discovered that in three weeks my fibromyalgia symptoms were subsiding substantially. My migraines, which had been sometimes two to three moderate to severe migraines a week, down to practically nil very quickly. I still had migraines, but they weren't nearly as severe. A lot of the different issues I had were subsiding and I thought ‘What's the deal here? Is this real?' Why, if this is real, why aren't more people experiencing it?

 

“But, the amazing thing I discovered was the change in my memories. I started remembering things — important things — things you aren't supposed to forget like the birth of your children. So I started investigating further.”

 

Pedersen continued delving into the benefits of cannabis until his learning journey became a crusade to educate others in 2006. “More people need cannabis because cannabis is actually a neuroprotectant and it helps people with memory and cognitive function,” he noted.

 

According to Pedersen, common perceptions of cannabis having the opposite effect of enhanced memory and cognitive function is largely due to the difference between how cannabis is used recreationally versus medicinally. “It has to do with the quantities they use and the methods they use in taking it,” he explained. “I can tell you first hand, if you were using large quantities, you would find that cognitive function would go up, and the euphoria [experienced] would go away.

 

“What I can tell you is that it also comes down to other factors. The quality of the cannabis that people get can make a lot of difference as far as the effects that we see. Understand, when we talk about the euphoria that people experience from cannabis, this is a side effect. This is actually an endogenous side effect, and the reason I say that is because it's why and the way it's affecting the body and to explain that I have to jump back and explain the cannabis plant has what is called a phytocannabinoid system.”

 

Endocannabinoids and phytocannabinoids

 

“All humans, actually all mammals including some invertebrates, have what is called an endocannabinoid system,” Pedersen said. “So, basically what this means is that we produce within our bodies chemicals that are very similar to the chemicals that are produced by the cannabis plant. This is particularly important. The phytocannabinoids produced by cannabis are not the same thing as the endocannabinoids, but the similarities are what make it so vitally important as a medicine.

 

“To give you an idea, the cannabinoid THC, in your bloodstream, and the endogenous chemical that you produce called anandamide — you cannot tell the difference between the two. The effects would be the same within your body, and that's particularly important because THC is the only active ingredient found in the cannabis plant. There are many other cannabinoids but they don't have the same effect as THC does because THC so accurately replicates the function of anandamide within the human body that's why it's particularly important.

 

“The effects of THC are felt when that chemical makes its way to those receptors within the brain, according to Pedersen. “The euphoria we experience is basically identical to the experience we have, what people call ‘runner's high',” he said. “Basically, that happens whenever anandamide is released into your bloodstream because you've exerted yourself and because one of the responsibilities of your endocannabinoid system is modulating the chemicals that repair our cells and strip away the waste and deal with the cells like cancer cells. That is part of the functioning or main functions of our endocannabinoid system.”

 

“Ignorance is people who don't understand what they're dealing with — what they're talking about when they are drafting state policy, and then you end up with all this twisted logic.”Mark Pedersen

 

Cannabis is food; food is medicine

 

According to Pedersen, in most cases when we talk about cannabis, people see through the eyes of pharmaceuticals or prescription drugs and this puts major limits on the cannabis discussion.

 

“When we deal with treating illness with prescription drugs we're dealing with poison, plain and simple,” he said. “When we deal with cannabis, cannabis is non-toxic and cannabis is actually a superfood even more nutritious than flax. So when we deal with cannabis, we're actually treating illness with food — nutrition, essentially. We're providing nutrition to our primary endocrine system — to our endocannabinoid system. So when we talk about what illnesses are we treating, basically what illness is in your body? What is it that your immune system is called into check?

 

“People have asked me, ‘Does cannabis treat Parkinson's disease?' I say ‘Yes.' They say, ‘Does it treat multiple sclerosis?' Yes. ‘Does it treat brain cancer? Stomach cancer? Prostate cancer?' ‘Yes' They go through the whole gamut and it's like, what is it that affects your body? What are the things that your immune system must deal with? Well, these are all the things that cannabis can assist us with because by fortifying our endocannabinoid system, we are aiding it in dealing with all of these issues. We produce cancer throughout our whole body throughout our whole life. We deal with cancer cells, you know, even in our mother's womb.”

 

Pedersen added that our endocannabinoid system is a major part of our primary endocrine system and is a crucial part of modulating the chemicals that control and maintain the body's homeostasis. The phytocannabinoids actually mimic the body's own endocannabinoids.

 

“If we produce cancer cells throughout our life, why is it at some point in time that suddenly now cancer is allowed to take — to run rampant?”, he asked. “And, we believe that the cause [of most cancer] is man-made — caused by the chemicals we ingest within the food we eat, prescription drugs, and other toxins we are exposed to. So, something affects our endocannabinoid system — throws it out of whack, it doesn't work the way it should — and then when we take large doses of phytocannabinoids, it's kind of like giving a super-charge to that system to kick it into working again. “And then we start seeing tumors shrinking — we start to see people responding remarkably.

 

“Cannabis as medicine hasn't come anywhere close to seeing where it's going to be from a commercial standpoint. Cannabis has the potential to replace upwards of 90 percent of the known pharmacopia — in so many different ways, because we are talking about a non-toxic substance treating terminal illness — treating debilitating illness. I have seen incredible miracles. I have stopped pediatric seizures in three minutes in my living room, when there was no drug on the market short of general anesthetic that could accomplish that task. Now, you may say that's bragging, but, I don't care. It's not me, it's the cannabis.”

 

Inside Knowledge

Did You Know?

More on cannabis
From The Cannabist: In 2016, we saw some important cannabis research published in top medical journals — research that flips the script on previously held beliefs and research that backs up what we’ve already seen anecdotally with medical cannabis. Here are some of the year’s most important scientific studies on cannabis:

Medical Marijuana Laws Reduce Prescription Medication Use In Medicare Part D

Pot-Smokers Harm Gums; Other Physical Effects Slight

Effects of Medical Marijuana on Migraine Headache Frequency in an Adult Population

Subjective Aggression During Alcohol and Cannabis Intoxication Before and After Aggression Exposure

GW Pharmaceuticals Announces Second Positive Phase 3 Pivotal Trial for Epidiolex (cannabidiol) in the Treatment of Lennox-Gastaut Syndrome

 

Cannabis and cancer

 

In addition to his commitment to changing both laws and perceptions, Pedersen plans to continue to utilize cannabis to help the people who come to him.

 

“I truly want to deal with legitimate illnesses, particularly terminal illnesses, that has become my focus, particularly children,” he said. “When patients come to me they are most often at Stage IV [of cancer], and at Stage IV they are already on chemotherapy and/or radiation. So, I'm not only dealing with the issues of the cancer, I'm also dealing with the issues of the traditional therapies the patient has already been undergoing. Treating the side effects of the chemo and radiation quite often eclipses the cancer.

 

“Wouldn't it be great if we lived in a world where when we had these terrible, terrible illnesses come about, like cancer, we chose the least volatile treatment first? And, why not choose the least volatile treatment first? Why not treat the cancer with food first? Then, if you don't see any development — if you don't see anything positive within a short period, then move on to the toxic substances. Why? Why not? Well, I'll tell you why not. And, the reason is because of expense. It's how much money our medical community rakes in from cancer therapy. A lot. This is really, truly the reason why we are not talking about the least volatile treatment first. Really, that's what we're talking.”

 

Cannabis can not only be an effective, valid cancer treatment, but also a first-line preventative measure, according to Pedersen.

 

“Cannabis affects a weakened and/or damaged endocannabinoid system, essentially supercharging it,” Pedersen explained. “The endocannabinoid system is responsible for dealing  with cancerous tumors, as well as basic cell health. Cannabis has actually been found to stimulate the production of endocannabinoids. Because it works with this endogenous system, it is effective in treating all forms of cancer – albeit, with varying levels of success based on the condition of the patient's heath, current damage from the cancer and conventional treatments, age, etc. Of course, cannabis oil is an excellent preventative treatment.  I have a family ravaged by stomach cancer. After losing one, too late to save him, I am now successfully treating a twin brother…preventative for another brother and sister.

 

“I wish more newly diagnosed cancer patients would try non-toxic cannabis first before moving onto toxic, neuro-damaging chemotherapy. However, most of the patients whom I treat with cannabis oil are taking it in addition to conventional therapies.  The fact that cannabis is nontoxic, makes it the perfect adjunct.

 

“Cannabis is a valid treatment for cancer — through the entire range of stages of cancers. Even at Stage IV, we are seeing miracles. We see the most astounding things. But the biggest factor I see with the patients I treat is improved quality of life. To be able to spend your remaining years, whatever number of years they be, with some quality of life — you enjoy your family and be able to go out peacefully, this is a very important factor, too.

 

“But, the real value that we are going to see in cancer cannabis therapies is going to come about when we really start seeing cannabis as food, because once cannabis is truly legal, and we can work with the amount — basically we get the price down on the plant material so everyone can afford it, we can start changing these things. Imagine a world where cancer is no more than an inconvenience. We know that patients can consume cannabis over extended periods of time because of the fact it's non-toxic and the fact it's a superfood and highly nutritious. They can consume it indefinitely. You can't do that with prescription drugs. You can't do that with these other therapies. Your kidneys and liver give out. I think cannabis stands the potential of replacing all cancer therapies. All cancer therapies.”

 

Utilizing cannabis therapy

 

 

There is a myriad of ways to utilize cannabis therapy including oral ingestion, suppositories, topical application, smoking, and vaping, according to Pedersen. But not all methods are created equal.

 

“When we smoke or vaporize cannabis, we take into our bodies upwards of 15 percent of the cannabinoids found in the cannabis,” Pedersen said. “When we eat cannabis, we take it orally, sublingually, or however, by mouth — we take into the body upwards of 30 percent of the cannabinoids that actually have medicinal value. When we take it orally, we also experience a great deal of euphoria, particularly if you don't take it regularly. Now, with suppositories, we get upwards of three times what you would get orally. You get 70 percent plus of the medicinal benefit from the cannabinoids. But, the other benefit you get from this is you get a dramatically reduced amount of euphoria and this has to do with the way it passes through in our rectum. Basically, the majority of the medication is making its way into the system, avoiding our liver, and by doing so we avoid much of the euphoria. So, you can understand that with the patients I'm working with, which are mostly end-of-life, Stage IV type scenarios, I'm really pushing the suppositories.

 

“When you are talking about topical applications, we have seen some really remarkable things with that. Much depends on the strength of the salve. We have seen a lot of salves you get in dispensaries that really aren't potent enough to do anything effectively. If the salves are potent enough, we see some remarkable benefits. It's perhaps one of the easiest ways to show patients the benefit of cannabis, particularly with people over the age of 50 or 60 years old. If you just allow them to apply a little bit to a knuckle, in 15 to 20 minutes they'll be back for more to apply to their hands and their other joints. The benefits are quite remarkable, increased mobility and much less pain with the topicals.”

 

“Understand, that there is no state in the country where cannabis is actually legal. Cannabis is not legal in Colorado. Cannabis is highly regulated here. It's still considered by law to be a harmful, dangerous drug.”Mark Pedersen

 

Cannabis is not marijuana

 

The term marijuana is actually a derogatory, slang term, according to Pedersen, and one he never uses. “It's a derogatory term given to cannabis back in the time when certain people — the powers that be — were seeking to make cannabis illegal for financial benefit,” he explained. “That is the reason why cannabis was made illegal in 1937 was because of that very reason. The term marijuana was adopted because they wanted to confuse people so people would not make the association with cannabis. In 1938, the American Medical Association petitioned the federal government to get a medicinal waiver for medicinal cannabis. Of course, Congress refused.

 

“It was all a smokescreen. Its original reason was because certain players had the opportunity to make many many millions of dollars by displacing an entire industry, and the industry we are talking about is the industrial hemp industry. DuPont had just come out with nylon a couple of years before and when we think about nylon, we think about clothing, but looking through 1930s eyes, when we are talking about nylon we would be thinking about synthetic rope. Well, in the 1930s they couldn't compete with hemp because hemp was a superior product all the way around.”

 

Hemp and cannabis are one and the same thing, according to Pedersen.

 

“Some years back, they began trying to change the vernacular so you'd hear the word hemp — understand that back in the 40s and before, it was all called hemp,” he said. “It was all hemp because it was all one plant. Now there are three different designations we find within cannabis. Basically, it's cannabis sativa, cannabis indica, and cannabis ruderalis. But, when we talk about cannabis as medicine, it quite often is a blending of all three. The reasons for that are because different strains grown for different purposes grow at different rates. Different stages have different levels of different cannabinoids and once they realized this, they began cultivating it to basically concentrate those particular products or benefits within the plant.

 

“From an industrial hemp level, we are talking about a product that can be used to produce a wide range of different things, everything from plastics to food to building supplies, it just goes on and on and on. But, it is not a separate thing as they have tried to make it out to [be]. It's insane. It's all one thing. It's all cannabis.”

 

 

The legislative battle

 

Much of the battle to change legislation boils down to education, according to Pedersen.

 

“This is part of what I'm seeking to change legislatively in the work I'm doing in drafting state policy, but it all comes back to education and understanding about what we're talking about when we're talking about cannabis,” he said. “Ignorance is people who don't understand what they're dealing with — what they're talking about when they are drafting state policy, and then you end up with all this twisted logic.

 

“Understand, that there is no state in the country where cannabis is actually legal. Cannabis is not legal in Colorado. Cannabis is highly regulated here. It's still considered by law to be a harmful, dangerous drug. That is very important. The federal government has, since 1971, a controlled substance list which basically rates them from Schedule 1 to Schedule 5. Every state in the union has their own list, and some states look to the federal government for that list. The state of Colorado is one of those states. It's actually in it's revised statutes where it says that when it comes to controlled substances we look to the federal government. That's really important because we have a state like Colorado where people think cannabis is legal.”

 

However, that is definitely not the case, according to Pedersen. In Colorado, cannabis is rated as a Schedule 1 drug. As a comparison, heroin is also considered a Schedule 1 drug.

 

“So, now we see this huge disparity in the law,” he said. “[In Colorado] we have a controlled substance Schedule 1 drug that is being sold by 21-year-olds in retail stores. Think about what it would be like if a store opened up down the street from you and started selling heroin. You would see the bars on the windows and bars on the doors. You would see the big armed guard that stands out front. Just like we're seeing with cannabis in Colorado. The only difference is, cannabis is non-toxic. If you were to consume a cannabis regimen of 60 grams in one sitting, you would have a very uncomfortable experience followed by a very long sleep. Then you would probably have a couple of days you would be walking around in a cloud, then you would feel like a million bucks. You would not die from it because cannabis cannot kill you. Cannabis is food. It's food.”

 

This stark contradiction in law and drug scheduling is one thing Pedersen has been addressing in his legislative initiatives for the past seven years. “Why we treat it this way is because these states continue to maintain that cannabis is a schedule 1 drug,” he explained. “If you read the initiatives that I've written, in every one of them the very first mission is the removal of cannabis entirely from the controlled substances because food doesn't belong on a controlled substances list.”

 

Drug scheduling is not the only hurdle facing Pedersen in his legislative journey, another major problem is what he calls “baby steps.”

 

“The problem we have encountered all along is that baby steps do not work,” he said. “When it comes to issues like cannabis, the problem is that with each step that you make you create ancillary industries that exist only because of prohibition. Now, let me explain. Where Colorado is can be considered a baby step. They are on their way toward full legalization, some would say. But, the problem is that maintaining cannabis as a Schedule 1 drug is imperative so they can maintain the same level of controls. There is special packaging that has been developed and endorsed by the state. It's always money. It's always money. So, we have companies that their only purpose is designing special packaging. That's why I call my bills — my initiatives that I've written, the latest one for 2018 — a reset button because if my initiative was to go into place, all of this would go away. We would go back to square one; cannabis would be treated as a food, as it was prior to 1937.”

 

Inside Knowledge

Did You Know?

ECS Therapy Center
The startling evidence of the ECS and the plethora of resulting scientific evidence that has followed has failed to morph the public dialogue about cannabis use from harmful, illegal substance to low-risk, non-toxic, potential health therapy or simple nutritional supplement for most, if not, all human beings. Nor, has public or professional education been a focus of policymakers. In short, the prohibition of cannabis has failed to become an issue of public health. Our mission is to develop a public health model for cannabis therapy.
Learn More

 

Battle of public perception

 

One of the major challenges facing Pedersen's efforts in getting cannabis legally reclassified is one of public perception. But, it is changing.

 

“In the events that I have held around the country, particularly in the Bible Belt, I'd say that 70 percent of those people are Sunday, go-to-church Christians,” he said. “I have taken and provided oil to a Kentucky Baptist preacher for his son. I have counseled with a Baptist preacher in a small town in Nebraska. I had a preacher in the middle of Oklahoma who his congregation was pooling cash to send one of their congregants who had cancer out to Colorado to get medication. I just met with a pastor here in Colorado who is hugely supportive of the work that I do.

 

“So, what we have here is we have a disparity in people's concepts. We have people who are within the cannabis community who truly don't think the rest of the world really would understand. But the fact is, the only reason people don't understand is because they just haven't received the education. How do we counteract that? We counteract it with education. We do it the same way in which cannabis was made illegal. It began becoming illegal in 1927, I believe it was, with California, and then by 1937, there were 20-some odd states that had pushed for these laws. And again, it all came about because of the fact that the people had no control in their own government. The lawmakers were determining these laws and passing them in the states' statutes. That's how cannabis became illegal.

 

“So, how do we change it back? We do it by working, particularly within those states that can do a direct initiative, where the people can truly decide their future and what the future of cannabis is, not crooked lawmakers.”

 

Changing cannabis' reputation as a drug that provides a “high” is another battle of misinformation and public misconception, according to Pedersen.

 

“People falsely compare it to the response we receive when we are talking about alcohol, but they are two completely different things,” he said. “When we consume alcohol it's held in our liver, as it's converted into a non-toxic substance — a substance that won't poison us. You know, even a spoonful of alcohol into our bloodstream will kill us. It has to be converted into a substance that our body can tolerate, and so when we consume vast amounts of alcohol what do we see? We see our liver swelling as it seeks to try to hold that alcohol — that poison — in there and not release it into the rest of our system. But, at some point, it cascades into our bloodstream and then it makes its way into our brain. What happens there? It begins killing our brain cells. That's poisoning.

 

“Well now, let's talk about cannabis in our systems. When we consume cannabis, it passes through our liver. Our liver sees it as food because that's rightly what it truly is. It's not only food, it's a substance that is familiar to our bodies. It's familiar because we produce these chemicals, endocannabinoids. OK, so what does our liver do? Cannabis passes right through the liver, and we consume what we need right then and then it stores the rest in our fat cells. This is why when in later times we exert ourselves and we need to call upon our endocannabinoids to repair our cells our body releases those phytocannabinoids stored up in our fat cells into our bloodstream. This is also why we can still test positive for cannabis sometimes weeks after we've consumed it — it's been stored away in our fat cells because our bodies naturally realize that cannabis is food.”

 

According to Pedersen,  the book “The eCS Therapy Companion Guide: A Reference Source for Your Endocannabinoid System”, written by Dr. Regina Nelson with contributions by Pedersen, is a great place to start if you want to learn the truth about cannibis. “It's available on Amazon,” he said. “Basically, what we sought to do with this book is to show the world the truth – to identify a lot of the falsehoods about cannabis, and to help people to understand that cannabis truly is food.”

 

But what about our children if cannabis becomes legal, or a “food”?

 

“We have a responsibility as parents to teach our children how we believe they should grow up,” Pedersen said. “And when we talk about cannabis, I can tell you that cannabis is non-toxic — that the euphoria we experience with cannabis does not harm us in any way, and that actually the longer we consume cannabis the less euphoria we experience — so, basically, it's negligible — it doesn't exist. Particularly among our children. Our children actually respond less quickly than we do as adults.

 

“So, the question comes down to, if you have an issue with your child experiencing euphoria, whether it's because of cannabis or any other substance, this is your personal duty as a parent to bring it up, to discuss it and also take and make sure your child adheres to those tenets that you personally subscribe to as a family. This is not something that is the duty of law enforcement or our court system because we are talking about food.

 

“Our schools and our law enforcement are not the ones who are supposed to teach the values to our children. We are supposed to teach values to our children,” Pedersen said. “We are supposed to instruct our children what is right and what is wrong. Laws are not in place to make children obey them. No. We instill those values in our children, as parents.

 

“You know, I raised three children. Not one of my children drank bleach or ammonia — none of those things. We never had a lock on the cupboard where those things were contained. Our kids knew where the Tylenol was in the medicine cabinet. They didn't go take it without talking to us first. They never even thought about doing that.”

 

Conclusion

 

The myriad of health and disease-fighting benefits of cannabis are almost impossible to comprehensively list, but it is clear it is an amazing weapon in the war against cancer. Cannabis, which is non-toxic, is proven to be an immune stimulant, an effective pain reliever, anti-nausea,  cancer-fighting, and appetite-stimulating nervous system tonic and superfood.

 

The battle to reclassify cannabis as a food and not as a scheduled drug is an ongoing and crucial one. Pedersen and others who share his views are fighting to bring cannabis to a place in our society where it is an available, affordable superfood that can help people successfully fight and prevent all manner of serious illnesses, including cancer.

 

Therapeutic Substance(s): 
Therapeutic intervention: 
Disease(s): 

Melatonin

field_vote: 

article sited from http://www.naturalnews.com/022981_melatonin_cancer_breast.html#ixzz1ORKeEIS1

(NaturalNews) Melatonin is nature's sleeping pill. It is secreted by the light sensitive pineal gland which regulates our biological clock and synchronizes our hormonal-immune network. Our level of melatonin rises with darkness and falls with light. According to Dr. Uzzi Reiss, in his book Natural Hormone Balance, a healthy pineal gland produces 2.5 milligrams of melatonin every twenty-four hours.

Melatonin plays a central role in the natural aging processes of the body. When pineal production begins to diminish, at around age 40, the decline sets off changes in the operation of the body's cells. The physiology of the cell shifts from repair and rejuvenation to aging and degeneration.

Recent studies are now showing that as our levels of melatonin sink, our chances for breast cancer rise. Many women with breast cancer have lower levels of melatonin than those without the disease. Laboratory experiments indicate that lower levels of melatonin stimulate growth of breast cancer cells. Adding melatonin to these cells inhibits their growth.

Breast cancer and melatonin: studies and results

According to a study at the Department of Physiology, Faculty of Science, University of Extremadura, Badajoz, Spain, published in Molecular and Cellular Biochemistry, Oct. 2005, melatonin increases the survival time of animals with untreated mammary tumors.

The aim of the study was to evaluate the therapeutic effect of melatonin on rats with advanced and untreated mammary tumors. Mammary tumors were chemically induced in rats. Following appearance of the tumors, the effect of melatonin was evaluated based on the survival time, tumor multiplicity, and tumor volume up until the death of the animals. Additionally, the variations in prolactin, noradrenaline and adrenaline concentrations, and percentage of NK cells were evaluated after one month of the melatonin treatment.

Results indicate that daily administration of melatonin increased significantly the survival time of tumor bearing animals compared to the control non-melatonin receiving rats. However, the lengthened survival time did not correlate with changes in either tumor multiplicity or growth rates. Animals with mammary tumors exhibited increased levels of prolactin and catecholamine concentrations compared to the healthy animals. The administration of melatonin stabilized the hormone levels, returning them to the levels of the healthy animals. Rats with mammary tumors also presented lower percentages of NK cells, however these levels were not increased with the administration of melatonin. Researchers concluded that melatonin is beneficial during advanced breast cancer. It increases survival time, perhaps by improving the homeostatic and neuroendocrine equilibrium which is imbalanced during advanced breast cancer.

As published in the International Journal of Cancer, January, 2006, researchers at the Department of Physiology and Pharmacology, School of Medicine, University of Cantabria, Santander, Spain, found that melatonin inhibits the growth of induced mammary tumors by decreasing the local biosynthesis of estrogens through the modulation of aromatase activity. They note that melatonin inhibits the growth of breast cancer cells by interacting with estrogen-responsive pathways, effectively behaving as an anti-estrogenic hormone. They had previously described that melatonin reduces aromatase expression and activity in human breast cancer cells, thus modulating local estrogen biosynthesis.

To investigate the in vivo aromatase-inhibitory properties of melatonin in the current study, the indoleamine was administered to rats bearing induced mammary tumors ovariectomized and treated with testosterone. In these castrated animals, the growth of the estrogen-sensitive tumors depended on the local aromatization of testosterone to estrogens. Ovariectomy significantly reduced the size of the tumors while the administration of testosterone to ovariectomized animals stimulated tumor growth, an effect that was suppressed by administration of melatonin or the aromatase inhibitor aminoglutethimide. Uterine weight of the rats, which depended on the local synthesis of estrogens, was increased by testosterone, except in those animals that were also treated with melatonin or aminoglutethimide. The growth-stimulatory effects of testosterone on the uterus and tumors depended exclusively on locally formed estrogens, since no changes in serum estradiol were appreciated in testosterone treated rats.

Tumors from animals treated with melatonin had lower microsomal aromatase activity than tumors of animals from other groups, and incubation with melatonin decreased the aromatase activity of microsomal fractions of tumors. Animals treated with melatonin had the same survival probability as the castrated animals and significantly higher survival probability than those not castrated.

Researchers conclude that melatonin could exert its antitumoral effects on hormone dependent mammary tumors by inhibiting the aromatase activity of the tumoral tissue.

And in the April, 2007 edition of Oncology Report, this same research team at the University of Cantabria, Santander, Spain, reports the effects of MT1 melatonin receptor over-expression on the aromatase-suppressive effect of melatonin in human breast cancer cells. They note that a major mechanism through which melatonin reduces the development of breast cancer is based on its anti-estrogenic actions by interfering at different levels with the estrogen-signaling pathways.

Transfection of the MT1 melatonin receptor in the breast cancer cells significantly decreased aromatase activity, and MT1-transfected cells showed a level of aromatase activity that was 50% of vector-transfected cells. The proliferation of estrogen-sensitive cells in an estradiol-free media but in the presence of testosterone (an indirect measure of aromatase activity) was strongly inhibited by melatonin in those cells over-expressing the MT1 receptor. This inhibitory effect of melatonin on cell growth was higher on MT1 transfected cells than in vector transfected cells. In MT1-transfected cells, aromatase activity was inhibited by melatonin. The same concentrations of melatonin did not significantly influence the aromatase activity of the vector-transfected cells. MT1 melatonin receptor transfection induced a 55% inhibition of aromatase expression in comparison to vector-transfected cells. Additionally, in MT1-transfected cells, melatonin treatment inhibited aromatase expression and induced a higher down-regulation of aromatase expression than in vector-transfected cells.

The researchers concluded that their findings point to the importance of the MT1 melatonin receptor in mediating the oncostatic action of melatonin in human breast cancer cells, and confirm the MT1 melatonin receptor as a major mediator in the melatonin signaling pathway in breast cancer.

Supplementing with melatonin

Since production of melatonin by the pineal gland begins to decline at age 40, it follows that anyone over the age of 40 may be melatonin deficient and may benefit from supplementation as a preventative. Since melatonin is produced while you sleep, it also follows that if you do not get enough sleep, your levels of melatonin may be deficient. Enough sleep is 8 or more hours. Supplementing with melatonin may also be indicated for those who now have or once had breast cancer.

Your melatonin level can be measured with a simple blood test.

According to Dr. Reiss, you should not take melatonin if you have exhausted adrenal glands, symptomized by constant fatigue, low blood pressure, feeling faint when standing up, and low tolerance for physical and emotional stress. Melatonin can reduce the production of cortisol and would be contraindicated for this condition. When adrenal glands are again healthy, supplementation can be started. Women who are trying to conceive should not take melatonin as it could negatively impact the ovulation process.

Melatonin supplements are synthesized to be bio-identical with your own melatonin. They are available at health food stores in capsules, sublingual drops, pills, and as an oral spray.

For anti-aging, Dr. Reiss recommends starting with 0.25 to 0.5 milligrams and increasing the dose gradually until you notice a side effect. The optimal dose is usually 1 to 5 milligrams.

Side effects from excess melatonin are drowsiness upon waking, wild dreams that are not pleasant, waking up nervous, sweating, or with palpitations, and decreased estrogen and progesterone levels.

There is disagreement among authorities as to whether higher doses of melatonin should be recommended for cancer prevention. Dr. Reiss recommends 20 to 40 milligrams daily for prevention. He notes that participants in studies using these very high doses did not develop the side effects seen at lower doses.

Dr. John Lee, in his book What Your Doctor May Not Tell You About Breast Cancer, says that high melatonin levels reduce the ovarian production of estrogens and progesterone, and this is the feedback that is thought to be protective against breast cancer. However, he stresses that all the body's hormones must be in balance, and more is not better when it comes to melatonin. He recommends supplementing with no more than 1 milligram of melatonin sublingually just before bedtime.

If you choose to rely on you own production of melatonin, be aware that production of melatonin rises from bedtime until the middle of the night, and then slowly declines throughout the rest of the night. This production is dependent on you sleeping in a dark room. If you get up during the night and turn on the light or open the refrigerator door, your melatonin production will abruptly stop.

Therapeutic Substance(s): 
Disease(s): 

Natural Anti-inflammatory Substances

field_vote: 

It is a well known fact that many disease conditions are related to chronic inflammation.

On this page, we will list all kinds of natural anti-inflammatory treatments.

Boswellia

field_vote: 
  1. Boswellia serrata

    From Wikipedia, the free encyclopedia
    Boswellia serrata
    Boswellia serrata (Salai) in Kinnarsani WS, AP W2 IMG 5840.jpg
    in Kinnerasani Wildlife Sanctuary, Andhra Pradesh, India.
    Scientific classification
    Kingdom: Plantae
    (unranked): Angiosperms
    (unranked): Eudicots
    (unranked): Rosids
    Order: Sapindales
    Family: Burseraceae
    Genus: Boswellia
    Species: B. serrata
    Binomial name
    Boswellia serrata
    Triana & Planch.

    Boswellia serrata is a plant that produces Indian frankincense, Salai, referred to in Sanskrit as shallaki and in Latin as Olibanum Indicum.[1] the plant is native to much of India and the Punjab region that extends into Pakistan.[2]

    Contents

    Medical usage

    In Ayurvedic medicine Indian frankincense has been used for hundreds of years for the treatment of arthritis.[3][4]

     

    Extracts of Boswellia serrata have been clinically studied for osteoarthritis and joint function, particularly for osteoarthritis of the knee, with the research showing a slight improvement of both pain and function compared to a placebo.[5] Positive effects of Boswellia in some chronic inflammatory diseases including rheumatoid arthritis, bronchial asthma, osteoarthritis, ulcerative colitis and Crohn's disease have been reported.[6] Some see Boswellia serrata as a promising alternative to NSAIDs, warranting further investigation in pharmacological studies and clinical trials.[7][8]

    Topical application

    Boswellia serrata has been recently developed for topical use in a patent-pending formula in Sano Relief Gel. Boswellia serrata is used in the manufacture of the anti-wrinkle agent "Boswelox",[9] which has been criticised as being ineffective.[10]

    Active constituents

    Boswellic acid and other pentacyclic triterpene acids are present. Beta-boswellic acid is the major constituent.

    External links

    References

  2. European Scientific Cooperative on Phytotherapy (2009). E/S/C/O/P Monographs: The Scientific Foundation for Herbal Medicinal Products. Second Edition, Supplement 2009. European Scientific Cooperative on Phytotherapy. p. 184. ISBN 9781901964080.
  3. "USDA GRIN Taxonomy". Retrieved 15 October 2014.
  4. "JOINT RELIEF". www.herbcompanion.com. Retrieved 2009-01-12.
  5. https://americanindianimports.com/content/9_shallaki-natural-anti-inflammatory
  6. Cameron, M; Chrubasik, S (May 22, 2014). "Oral herbal therapies for treating osteoarthritis". Cochrane Summaries. Retrieved June 6, 2014.
  7. Ammon, HP (2010). "Modulation of the immune system by Boswellia serrata extracts and boswellic acids". Phytomedicine. 17 (11): 862–7. doi:10.1016/j.phymed.2010.03.003.
  8. Abdel-Tawab, M; Werz, O; Schubert-Zsilavecz, M (Jun 2011). "Boswellia serrata: an overall assessment of in vitro, preclinical, pharmacokinetic and clinical data". Clin Pharmacokinet. 50 (6): 349–69. doi:10.2165/11586800-000000000-00000. PMID 21553931.
  9. Siddiqui, MZ (2011). "Boswellia serrata, a potential antiinflammatory agent: an overview". Indian J Pharm Sci. 73: 255–61. doi:10.4103/0250-474X.93507. PMC 3309643Freely accessible. PMID 22457547.
  10. Wrinkle breakthrough claim from L'Oreal
  11. L'Oreal slammed over cream claims
Therapeutic Substance(s): 
Therapeutic intervention: 
Disease(s): 

Curcumin

field_vote: 

From www.cancertutor.com

Turmeric is widely used in India as a spice and has been around for more than 4,000 years. It is a cornerstone of Ayurvedic medicine and other traditional medicines from around the world. Turmeric is not spicy, as some people may think, but is used to add a rich flavor to foods.

It is the common ingredient in many curries. Grown as a root crop, it can be used as a root directly (as it often is in cooking) or converted to a powder for use as a spice. For example, turmeric seasons yellow curry at Thai restaurants and a variety of curry dishes at Indian restaurants. Commonly known as the “yellow-colored spice,” it is even used as a natural coloring agent in foods in the United States, for instance in French’s mustard and other products that have a yellow color.

When using turmeric as a food (or dietary supplement), one should take into consideration important factors such as whether it is synthetic, GMO, or grown with the use of pesticides and herbicides. Further, turmeric is available in many grades, ranging from very good to very poor. To get the benefits of turmeric, one must choose the right cultivar.

Turmeric is a very powerful adaptogenic and anti-inflammatory compound when grown and processed responsibly. Its many health benefits come from a powerhouse compound in its root: curcumin.

Curcumin — a vital component of turmeric

The most vital therapeutic component in turmeric is curcumin.  Although curcumin was described more than a century ago, the last two decades have seen an explosion of research into the compound and its numerous health benefits. Currently there are more than 8,000 published studies on turmeric and curcumin, making it one of the most researched natural ingredients. Curcumin has been shown to have more than 600 potential health benefits despite making up only 2-5 percent of the turmeric root on average.

Curcumin Targets

As you can see from the above diagram, curcumin provides both a multitargeted and monotargeted approach to its therapeutic actions. [1] Multitargeted means that curcumin works on hundreds of biochemical processes. For example, it works on transcriptional factors, protein kinases, adhesion molecules, enzymes, and inflammatory cytokines through its multifunctional actions and effects. Monotargeted means that, like conventional pharmaceuticals, curcumin works specifically on single-targeted pathways. Additionally, curcumin works by inhibiting the same pathways as NSAIDs — in addition to more than 100 other inflammatory pathways — without the unwanted effects.

For those who are interested in the scientific specifics, curcumin has been shown to reduce inflammation via NF-kB a major switch which plays an important role in health and disease (see image below). In addition, curcumin reduces COX-2, 5-LOX, C-reactive protein, IL-1 beta, IL-6, IL-12, TNF-alpha, IFN-gamma, AP-1, macrophage inflammatory protein, matrix metalloproteinase, human leukocyte elastase (HLE), several types of protein kinases, adhesion molecules, and genes involved with inflammation — to name a few (see image below). In addition to reducing and inhibiting factors that aggravate health conditions, curcumin also activates important protective factors such as Nrf2.

NF-kb Role in Health and Disease

Bosmeric-SR inhibits COX and LOX

 Other protective factors include curcumin’s demonstrated ability to boost antitumor immunity through different mechanisms. These include: increased population of CD8+ and CD4+ T cells, along with increase in Th1 cytokines like IFNγ, which mediate tumor cell apoptosis. Curcumin can block Treg cell development, thereby decreasing immunosuppressive cytokines like IL-10 and TGFβ. Curcumin also reduces tumor-induced T-cell apoptosis. All these actions help to invalidate the overall immunosuppressive environment created by a tumor (which is how the tumor avoids being recognized by the immune system) and lead to tumor regression. Thus curcumin has the ability to provide a favorable response by supporting the immune system and restoring immune system-mediated elimination of tumors. [2]

The foregoing explanation is heavy on scientific terminology. In simple terms, curcumin has been shown to exhibit the following properties: [3]

  • Antioxidant
  • Anti-inflammatory
  • Antiviral
  • Antibacterial
  • Antifungal
  • Anticancer

The above effects are mediated through the regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other enzymes. For those who have severe chronic inflammatory health conditions—such as rheumatoid and psoriatic arthritis, Crohn’s disease, ulcerative colitis, and even some cancers—you probably have been treated with pharmaceutical immunosuppressive agents and anticancer agents, offering some benefits along with heavy side effects and a large list of black-box warnings (see The Dangers of NSAIDs: Black Box Warning) . Curcumin has been shown to work similarly to these powerful medications, but without unwanted and unpleasant side effects.

Curcumin: A natural pharmaceutical without side effects?

Curcumin exhibits activities similar to an astonishing number of major pharmaceutical anti-inflammatory drugs and chemotherapy drugs, including (but far from limited to) the following: COX-2 inhibitors (Celebrex), TNF blockers (Humira, Remicade, and Enbrel), vascular endothelial cell growth-factor blockers (Avastin), human epidermal growth-factor receptor blockers (Erbitux, Erlotinib, and Gefitinib), HER2 blockers (Herceptin), topoisomerase inhibitors (Camptothecin), tubulin inhibitors (paclitaxel, Taxol), and BCR-ABL1 tyrosine kinase inhibitors (Gleevec) — without side effects.* In fact, there are no reports of death or serious injury from the consumption of turmeric or curcumin — just millions of tasty meals. [4]

So promising is the therapeutic potential of curcumin that a recent turmeric study published in Cancer Letters is paving the way for a revolution in the way that we understand and treat cancer, titled “Targeting Cancer Stem Cells by Curcumin and Clinical Applications.” [5] Researchers in the United States demonstrated via many cell and animal studies that curcumin has the ability to target cancer stem cells (CSCs), getting to the root cause of tumor formation and malignancy. [6]

CSCs are the deadliest cell types within a tumor or blood cancer, since stem cells have the ability to give rise to all the cell types found within a particular cancer. CSCs are capable of dividing (by mitosis) to form either two stem cells (increasing the size of the stem population) or one daughter cell that goes on to differentiate into a variety of cell types and one daughter cell that retains stem-cell properties. This means that CSCs are tumorigenic (tumor forming) and tumor sustaining. Therefore, it makes good medical sense to focus cancer therapy on treating the disease at this level. CSCs are also increasingly recognized to be the cause of relapse and metastasis following conventional cancer treatment.

Turmeric and curcumin extract have been extensively studied for their ability to kill various cancer-cell lines. Research identifies a number of ways in which curcumin provides an ideal CSC-targeting therapy, including the following: [7]

Regulation of the CSC self-renewal pathway: Curcumin appears to directly and indirectly influence at least three self-renewal pathways within cancer stem cells, namely Wnt/b-catenin, sonic hedgehog 89 (SHH), and Notch. The authors list 12 different cancer-cell lines that curcumin appears to affect positively.

Modulation of microRNA: MicroRNAs are short noncoding RNA sequences that regulate approximately 33 percent of the protein-coding genes in the human genome. They bind to target messenger RNAs (mRNAs), leading to their degradation or inactivation. Curcumin has been found to alter the expression of microRNAs in cancer stem cells in a way that would suggest a strong suppression of tumor formation.

In addition to the dozens of anticancer activities that curcumin has demonstrated, it also acts as a chemotherapy and radiation-therapy sensitizer. This means that it helps sensitize the tumors to cancer therapies, making those treatments more effective. In other words, making toxic therapies more targeted. Curcumin can sensitize tumors to many different chemotherapeutic agents, including doxorubicin, 5-FU, paclitaxel, vincristine, melphalan, butyrate, cisplatin, celecoxib, vinorelbine, gemcitabine, oxaliplatin, etoposide, sulfinosine, thalidomide, and bortezomib.

Chemosensitization has been observed in cancers of the breast, colon, pancreas, GI tract, liver, blood, lung, prostate, bladder, cervix, ovary, head, neck, and brain, as well as in multiple myeloma, leukemia, and lymphoma. Similar studies have also revealed that curcumin can increase the sensitivity to gamma radiation of a variety of tumors, including glioma, neuroblastoma, cervical carcinoma, epidermal carcinoma, prostate cancer, and colon cancer. How curcumin acts as a chemosensitizer and radiosensitizer has also been studied extensively. [8] For example, it downregulates various growth-regulatory pathways and specific genetic targets, including genes for NF-kB, STAT3, COX-2, Akt, antiapoptotic proteins, growth-factor receptors, and multidrug-resistance proteins. [9]

Furthermore, curcumin also helps protect healthy tissues from the toxic side effects of chemotherapy and radiation therapy. Curcumin has been shown to protect healthy organs and tissues such as the liver, kidney, oral mucosa, and heart from chemotherapy- and radiotherapy-induced toxicity. The protective effects of curcumin appear to be mediated in a variety of ways: through activating Nrf2 and inducing the expression of antioxidant enzymes (e.g., heme oxygenase-1, glutathione peroxidase, modulatory subunit of gamma-glutamyl-cysteine ligase, NAD(P)H:quinone oxidoreductase 1, and increase glutathione — a product of the modulatory subunit of gamma-glutamyl-cysteine ligase), directly quenching free radicals, and inhibiting p300 HAT activity — to name a few. [10]

To summarize all that dense scientific language, curcumin exhibits some of the most amazing anticancer properties, such as the following, which apply to most cancers:

  • Inhibits TNF-alpha, NF-kB, and hundreds of other mechanisms that stimulate inflammation [11]
    • As little as 150 mg of curcumin twice daily, standardized to three curcuminoids orally, can significantly decrease TNF-alpha [12]
  • Prevents multidrug-resistant cancers [13]
  • Destroys cancer stem cells (CSC) [14]
  • Protects tissues and organs from chemotherapy- and radiation-induced damage (reducing overall toxicity from these treatments) [15]
  • Works synergistically with chemotherapy and radiation therapy to make those therapies more targeted and, therefore, more effective. [16]

In addition to inhibiting and influencing the biological mechanisms of inflammation as described earlier, curcumin has been shown to improve endothelial function and reduce vascular inflammation (which increases blood flow and prevents plaque buildup in the arteries), downregulate adipokines (including resistin and leptin, factors involved in obesity) and monocyte chemotactic protein-1, and upregulate Nrf2 (key factors involved in brain-inflammatory processes and brain-degeneration issues that manifest in disorders such as epilepsy, Alzheimer’s, traumatic brain injury, and other neurodegenerative conditions).

So what does all this mean in terms of preventing and treating disease? It means curcumin may be the most powerful natural therapeutic substance for a wide array of acute and chronic health conditions.

Conditions helped by curcumin*

  • Osteoarthritis
  • Autoimmune arthritis (rheumatoid)
  • Ulcerative colitis and Crohn’s disease
  • Cancer (breast, prostate, brain, colon, bone, and liver), via immune-modulating, angiogenesis, tumorigenic properties
  • Allergies and asthma
  • Diabetes and diabetic neuropathy
  • Cardiovascular diseases
  • Obesity
  • Fibromyalgia and other chronic-pain syndromes
  • Neurodegenerative diseases (Alzheimer’s disease, Parkinson’s, traumatic brain injury, epilepsy, etc.)
  • Acne, psoriasis, and eczema
  • Liver diseases (toxic insults and dysfunction)

Which form of curcumin is best for me?

Now that you know some of the amazing benefits of curcumin, and you’ve seen that there is a lot of low-quality curcumin on the market, how can you tell what is best?

The gold standard for curcumin is called Curcumin C3 Complex, (which is part of Bosmeric-SR formula; see The Vital Role of Boswellia (Frankincense) for Cancer).  It is the patented form of curcumin that contains standardized 95 percent curcuminoids and is supported by 50 human clinical studies (and counting) at major universities, hospitals, and health-care institutions worldwide, making Curcumin C3 Complex the most clinically studied brand of curcumin on the market today.

Curcumin C3 Complex is not only the most effective form of curcumin and the most clinically studied but also contains the three major constituents (curcuminoids) in specific ratios, guaranteed:

  • Curcumin (70-80 percent)
  • Bidemothoxy curcumin (2.5-6.5 percent)
  • Demethoxy curcumin (15-25 percent)

These three curcuminoids are guaranteed to be in the same ratios in every batch, which is almost unheard of in the natural-product world. Most importantly, these curcuminoid ratios are also the precise ratios that have undergone the most clinical studies. This guaranteed uniformity ensures consistency of health benefits and enables physicians to more accurately recommend and administer these incredibly beneficial compounds.

What about generic curcumin extract standardized to 95 percent curcuminoids?

If you’re familiar with curcumin supplements, then you’re familiar with the ways in which companies try to assure consumers that they’re getting what they’re paying for. Most companies use generic “standardized 95 percent curcuminoids,” but that standardization doesn’t guarantee that the curcuminoid ratios are exactly in the proportions that have been clinically studied. In fact in a recent study in 2016 on the “Strong Anti-inflammatory Effects of Curcumin” by Vetivicka and Vetivickova, demonstrated that only Curcumin C3 Complex had both anti-inflammatory and immunological activity in comparison to four other brands of generic 95 percent curcuminoids in both vitro and vivo testing.

The study showed the other major brands and sources of generic 95 percent curcuminoids had little to none inflammatory and immunological activities. Thus not all curcumins available are equal.  The reason for the difference it is not the just the total amount of the three specific curcuminoids that was patented in Curcumin C3 Complex but also the process on how they are extracted.  Therefore since generics cannot extract the curcuminoids in the same way, their physiological benefits differ and in this case there is little to no activity.

This explains why in the clinical trials there are benefits to lowering inflammation through a variety of mechanisms and improving cancer outcomes but many people in the public do not obtain this benefit when they use generic 95 percent curcuminoid products. Thus generic standardization limits the effectiveness and purity of most curcumin supplements. Generic curcumin has no potency guarantee and is not validated by third-party testing; most supplements fall short of efficacy and safety measures. With this recent study, it proves again the difference between real science of proven natural patented ingredients and the ineffective generic products that are heavily marketed.

Supplement manufacturers from China and India, driving the marketplace to provide the cheapest product possible, generally purchase generic curcumin products. In this competitive international marketplace, corners are cut to further drive down costs; the most basic cuts are to safety (not testing enough or at all) and efficacy (not verifying clinical effectiveness).

Most companies (including MLM companies, health-practitioner channels, and retailers) will purchase generic curcuminoids not knowing (or caring) which type of turmeric they come from, how the turmeric is grown (whether pesticides, herbicides, GMO, or synthetics were used), whether harmful solvents were used for the extraction process, whether the product was irradiated, or whether or not the curcuminoids are effective. All that matters is the bottom line and having a “buzz worthy” ingredient. Thus by providing a substandard material and citing the clinical studies done on Curcumin C3 Complex as also applicable to their curcumin, these generic suppliers are misleading the consumers.

Remember, the FDA classifies a dietary supplement as “not intended to treat, prevent, or cure disease.” This limitation actually works in unscrupulous supplement companies’ favor. Since the FDA has defined what a supplement can’t do, supplement manufacturers can take advantage of this disclaimer by obtaining the cheapest (even completely ineffective) product because they are not being held to any standard of efficacy, potency, or purity. In essence, they don’t have to provide products that actually work anywhere close to how they are marketed.

Curcumin C3 Complex (see The Vital Role of Boswellia (Frankincense) for Cancer) contains only this proven form — the curcumin supported by the most safety data. This safety data has been reviewed and acknowledged by the FDA for GRAS (generally recognized as safe) status, a process that includes a comprehensive review of safety and toxicology data. Most other curcumin products on the market cannot make that claim.

Because Curcumin C3 Complex is made using a patented and proprietary process, the safety data for Curcumin C3 Complex is not applicable to other curcumin products. In fact, many other curcumin-supplement companies derive their indirect and direct health claims and advertising from research studies using Curcumin C3 Complex and not their own products! And you may see other curcumin products advertise that their curcumin is touted to be safe, but I recommend using Curcumin C3 Complex found in Bosmeric-SR, which is the only one that is guaranteed safe.

The use of turmeric and curcumin supplements has skyrocketed because of the enormous amounts of research published on a near-weekly basis (again, there are over eight thousand studies). Curcumin is one of the top five best-selling herbal ingredients every year. Because of this high demand, many companies and products state that they use curcumin, but, in actuality, their curcumin compounds are not as potent, as effective, or even as safe. The only one I recommend is found in Bosmeric-SR (see The Vital Role of Boswellia (Frankincense) for Cancer).

Natural versus Synthetic

As I touched on in the previous section, because of the competition in the marketplace and the drive for higher profit margins, you might have thought you tried Curcumin C3 Complex in the past. Over the past few years, companies have been caught claiming Curcumin C3 Complex on their label when in fact they were selling generic curcumin, synthetic curcumin, or turmeric extract. More nefariously, some companies have added a small amount of Curcumin C3 Complex to their product but illegally cut the product with generic curcumin, synthetic curcumin, or turmeric powder to make the margins on the product better.

This year synthetic curcumin was discovered being sold as turmeric extract with forged certificates of analysis. A major company selling curcumin extract in India for export to the United States was adulterating their product with synthetic curcumin (43 percent). What makes it worse is that the company was not revealing the synthetic contents. This leads one to a few obvious questions. What was it synthesized from? What chemicals were used? What process did they use to make it? And the most important question: is it safe for consumption by humans?

Synthetically made materials may have distinctively different pharmacological activities compared to natural products. If a company is selling synthetic curcumin and not identifying that some or all of the product was synthetically derived, that lack of transparency is not only misleading consumers who think they are taking a product derived from turmeric root, but it has the potential to hurt people.

Therefore, in order to avoid questionable contract manufacturers, I prefer to go directly to the source of ensuring each batch is consistent and guaranteed every time.  This is what you get with Bosmeric-SR, 100 percent guaranteed of the right form (purity) and dose (potency) of Curcumin C3 Complex each time you take it.

In a time when it seems everyone is trying to make a fast buck on supplements, transparent quality control and safety protocols have never been more important. Curcumin C3 Complex (as well as Bosmeric-SR) is manufactured in an FDA-inspected facility compliant with CGMP (the FDA’s standard for “current good manufacturing processes”). Its manufacturer maintains quality through the sourcing of raw material; they have direct control and access throughout the sourcing and manufacturing process. They use only analytical and biological testing labs audited and certified by the National Accreditation Board for Testing and Calibration Laboratories (NABL). Bosmeric-SR is manufactured in state-of-the-art facilities assessed by NSF International and certified to be in compliance with GMP. [17]

Again, although all manufacturing facilities should be up to these standards, because of the staffing limitations of the FDA and other regulatory agencies (since there are hundreds of contract manufacturers opening all over the country on a regular basis), not all companies actually comply with current FDA regulations.

Whether you decide to use Bosmeric-SR or not, it is important that you know the guidelines and the regulations that all supplements should abide by. The more informed we are, the higher standards these companies will have to hold themselves to if they want to stay in business.

What about the newer forms of curcumin that claim to be better absorbed?

Many companies claim to be selling newer forms of curcumin that they advertise as “new and improved,” “better absorbed,” and “more bioavailable” products. The industry uses these new buzzwords to help sell products, but as you might imagine, they aren’t necessarily providing the results they’re promising. I am not saying that some products do not have additional benefits or even improve on the benefits of a previous formulation. But when I started looking into actual formulations and actual data for “better absorbed” curcumin, what I found was shocking.

Bioavailability: A path and not a destination

The supplement industry has placed a disproportionate emphasis on the role of bioavailability of their formulations, but bioavailability is not the sole criterion for judging the therapeutic effect of curcumin.  Bioavailability is the amount of a substance (in this case curcumin) that is absorbed and made available at the site of physiological activity.  Therefore increasing bioavailability is important, but making sure that the substances, which are measured, also have health benefits is critical.

Vast amounts of research, along with the expert opinions of those who specialize in the field of curcuminoids, have continually maintained that bioavailability is only a “path” and not the “destination.” Enhanced bioavailability cannot be used as an alternative to or as a substitute for clinical studies. Now, I am interested in increasing bioavailability with all my products (see article on Black Pepper), and I also favor those companies that have invested in making their products more bioavailable. But these companies must have also initiated, supported, and invested their resources in several curcumin-based clinical trials. Science trumps buzzwords, always.

Formulations that contain curcumin-phosphatidyl choline, curcumin-lecithin, and micronized and micelle-curcumin mixtures deliver curcumin as a small fraction of the actual mass (most offer less than 20 percent curcuminoids; one even provides only 7 percent). Although the studies on these products show some benefits (as they should, since they are providing some curcumin), their claims of “29 to 60 times to even “185 times more absorbed” contain flat-out skewed data.

When curcuminoids are absorbed in the body, they are converted to many byproducts or metabolites such as glucuronides. Studies of these newer formulations are measuring not the actual curcuminoids but these other metabolites. They are using the increase in the metabolites to show increased absorption, but they are not actually providing those metabolites directly. For example, the above formulations do not inhibit the biotransformation of curcuminoids, which is the limiting factor for improving bioavailability. Instead, these formulations just load the body with more of the inactive glucuronide metabolites of curcuminoids. Additionally, many of these metabolites have been recently discovered to have little to no anti-inflammatory effects! [18]

Companies routinely misrepresent data and skew it to exaggerate the comparisons between formulations — especially in relation to other products. In fact, pharmaceutical companies may be the biggest offenders in this area. According to a handful of medical studies on the pharmaceutical industry, most of the comparison graphs and data that pharmaceutical sales reps and advertisements presented to doctors were not accurate. [19]

If this happens within the pharmaceutical industry — which the FDA regulates — you can imagine what happens when there is no regulation or oversight for such marketing from dietary-supplement companies. Exaggerated graphs and data are shown every day in supplement advertising and by sales reps. Store clerks, doctors, and the general public have probably seen a chart that shows “increased absorption” or “better bioavailability.”

Often these charts are comparing apples to oranges. As one example, I was presented with studies on curcumin that showed increased absorption rates, but those higher rates were for curcumin in a liquid versus a tablet form, and the company giving the presentation sold only tablets. This is a common trick in which sales representatives extrapolate data from one form or type of supplement and try to use it to their advantage; most products, when taken as a liquid, deliver better absorption than as a solid. In the case of this tablet company, however, they were attempting to misguide me with inaccurate data that made their product look better than it was.

Another newer form of curcumin uses something called “colloidal dispersion technology” and states that it has “enhanced absorption and bioavailability up to twenty-seven times.” A sales rep from the nutraceuticals company marketing this product arrived at my office and tried to tell me that this new curcumin was superior to anything else on the market. He had a colorful graph showing that it was “twenty-seven times” more absorbable than “regular” curcumin.

He did not know that I was familiar with the study used for the infographic. In that study, the authors tested their newer form of curcumin (which contained far less curcumin than most brands) against a turmeric product, but they (purposely) never stated the actual quantity of curcuminoids that the comparison product contained — only that theirs dissolved better in water. Thus, the rep was using an invalid comparison, which is sadly all too common.

Aside from that, however, this salesman didn’t mention that his product contained far fewer curcuminoids, and he declined to disclose the product’s sources. On top of that, a supplement that disperses better in water does not necessarily correlate to improved efficacy or absorption in the blood. What does this mean to the consumer? It means that dietary-supplement companies that sell these sorts of well-marketed “more bioavailable” products can make bigger claims and bigger profit margins while using lower potency or lower amounts of curcuminoids.

Another wrinkle in the bioavailability competition is the rise of lipid- or nano-encapsulated ingredients. These processes take standard ingredients and encapsulate them in tiny absorbable particles, making them smaller and more dispersible. Nanoparticles may be beneficial, although they certainly have their detractors, but with curcumin I tend to use what is tried and true. To date, no nanoparticle curcumin has been studied against Curcumin C3 Complex — just generic, nonstandardized curcumin powder or extracts without disclosed potencies. Generic forms never test against patented forms. Again, be wary of unsourced supplement studies and read very carefully between the lines—especially when it comes to an extremely popular compound like curcumin.

When assessing the bioavailability of curcumin in the body, ignoring the role of curcumin’s metabolites reveals a lack of knowledge and expertise. Curcumin breaks down into certain metabolites, which are mainly tetrahydrocurcumin, curcumin glucuronides, and sulfates. While the positive effects of tetrahydrocurcumin have been recognized, most bioavailability studies have failed to quantify the bioconversion of curcumin into this efficacious metabolite, tetrahydrocurcumin. [20]

This means that most studies are not giving the full therapeutic picture. The bioefficacy of glucuronides and sulfate metabolites, which is what the newer forms of curcumin formulations are claiming are better absorbed, has not been well established. They even have been shown to be less active and have weak activity. [21] Furthermore, they have no anti-inflammatory effects, nor do they have any effect on mitotic catastrophe, an important step in preventing proliferation of some cancerous cells. [22]

A world-renowned cancer and inflammation researcher in natural therapeutics announced at a recent cancer conference that his research demonstrated that “curcumin glucuronides show very little antiproliferative activity against human cancer-cell lines and have no inhibitory effect on NF-kB, thus lacking the anti-inflammatory activity of curcuminoids.” [23]

Although many products sold in health-food stores, on the Internet, through MLM companies, and through doctors’ networks may claim better absorption, they are measuring curcumin metabolites — especially the glucuronides — and thus are missing the stronger intended anti-inflammatory effect. In the real world, such absorption claims have nothing to do with efficacy; they’re simply the stuff of cleverly written research articles, with graphs that seem to illustrate meaningful differences, and very convincing marketing campaigns. Again, instead of searching for the “new and improved,” I tend to go with what has been tried and true — and backed by research.

Since many products are being introduced into the market almost monthly, and it would be impossible to go through all the comparisons here, I have provided comparisons on the most popular curcumin products being sold on the market which is described in detail in my book An Inflammation Nation.

Comparison of Curcumin in Bosmeric-SR vs Other Curcumin Products 1

Comparison of Curcumin Bosmeric-SR vs Other Curcumin Products 2

Turmeric cultivation and processing: What is best?

Since so many supplement companies focus on marketing “better absorption,” maybe we should ask them, better absorption of what, exactly? What type of curcumin are they using, and how is it cultivated and processed? You might make a smoothie with a high-quality blender such as a Vitamix, but that doesn’t mean that the smoothie is good for you — especially if it contains conventional, nonorganic, and GMO foods. What makes a smoothie better for you is not just the quality of the blender but, more importantly, the quality of the ingredients.

Most companies that sell curcumin products have no control of the actual turmeric crop, nor any control over how it is cultivated (e.g., with pesticides, herbicides, radiation, or GMOs). These companies only worry about getting the cheapest raw ingredients from the world market (mainly from China) and then trying to improve upon them with their proprietary processes.

However, when using foods as medicine, starting with the best ingredients makes the biggest difference. The curcumin in Bosmeric-SR is controlled, from crop cultivation at the farms to the highest certified processing facilities, to a patented process of extracting the specific ratio of curcuminoids — guaranteed batch to batch — to the manufacturing of the unique delivery system. All of this ensures a superior product that is consistent, potent, pure, and effective every time.

Taking things a step further, I have ensured that the Curcumin C3 Complex in Bosmeric-SR is not irradiated. Here’s why this is vitally important.

Many people are not aware that since 9/11, all food ingredients imported into the United States must be irradiated to ensure “safety” and destroy contaminants (bacteria, fungus, etc.). I have researched extensively and traveled to India (where most of the turmeric is grown) and discovered that almost all curcumin — especially curcumin grown in China, which is the second largest producer — is irradiated prior to being sent to the United States. My experience in India was truly disheartening. During my search for the best type of turmeric/curcumin, I witnessed many batches of raw product being sent to facilities to get irradiated. At these various facilities (which irradiate products and then provide certification of the completion of such treatment), there was no difference in the amount of radiation used to sterilize each different product.

For example, I personally witnessed the irradiation of a variety of herbal turmeric products from the biggest exporters in India (exporters that provide turmeric/curcumin to the major retailers and common brands at the health-food stores). These exporters have their products irradiated at the same dose that is used to sterilize surgical equipment. We are all familiar with the harmful effects of extreme doses of radiation, and sterilizing the herbal ingredients at that extreme level dramatically decreases the effectiveness of the antioxidants, phytonutrients, and other important aspects.

Curcumin C3 Complex is also non-irradiated to preserve the therapeutic benefits that are stripped out by massive doses of “protective” radiation. It does cost more to obtain certifications and to follow extremely strict importation procedures to ensure that there are no contaminants (bacteria, fungus, etc.) without irradiating anything. Naturally, it takes extra money, time and steps of quality control, but it is worth it to provide the true benefits of these incredibly powerful natural ingredients. Most of my patients who have tried other turmeric supplements said they did not work as well as they expected, but almost all reported that when they took Bosmeric-SR, they noticed an immediate and ongoing difference.

Not only does Bosmeric-SR have ensured potency and efficacy because it uses Curcumin C3 Complex, but it also has guaranteed safety from contaminants like heavy metals. Heavy metals? How do they wind up in any supplement? When supplement manufacturers request turmeric, the bulk spice is shipped to the United States in large containers. During the past few years — especially in 2008, 2011, and again in 2013 — independent consumer groups discovered that 33 percent of turmeric and curcumin supplements failed quality testing, and many popular brands contained lead and other contaminants. [24] Turmeric was being shipped in lead containers (mostly from India and China), and the containers’ linings were leaching lead into the turmeric. Makes you wonder about other foods, such as grains, shipped in those containers.

During the time of greatest lead contamination, many patients who came to see me were taking turmeric supplements for their joint pain. They told me they were taking it because they had read all the health benefits, but they felt that they were actually getting worse. No surprise: they were taking products from companies whose turmeric/curcumin products failed safety tests for lead contamination. Even worse, the patients had high levels of lead when we screened them using blood testing. This is a tragically obvious example of why purity is so important.

You will almost always get what you pay for. Sometimes a bargain costs you far more in the end. Remember, by the FDA’s own definition, “Dietary supplements are not intended to prevent, treat, reverse, or cure any disease.” Far too many companies follow that rule, but not to avoid getting in trouble for making sensationalistic health claims; instead they use the FDA’s disclaimer to absolve them of providing high-quality, effective, or safe products.

Furthermore, it is important to make sure that no harmful, toxic solvents are used in the process of extracting real curcumin from turmeric, as solvent residues do remain on extracted products and can cause harm. No harmful solvents are used in the extraction of the Curcumin C3 Complex used in Bosmeric-SR. Again, this processing is an investment in the health of anyone taking Bosmeric-SR; it costs slightly more to make a cleaner and safer product than to use cheap, poisonous chemicals, but it’s an investment worth making for so many reasons.

In addition to checking purity and quality of source, one must make sure that they’re getting real curcuminoids from real turmeric. Companies in China and India can make synthetic curcuminoids in the laboratory, creating something like a pharmaceutical compound. This is why you see turmeric/curcumin products priced as low as $2-5 for a bottle on the Internet. These cheap products are usually synthetically derived; you are taking an isolated molecular compound, and therefore, you are not receiving the full benefits of the curcuminoids — as well as the other active turmeric compounds.

Cheaper products mean that more harmful chemicals have been used in the production process, and, thus, they expose you to greater risk of side effects and allergic reactions. Next time you see a cheap generic turmeric product, see if the word “natural” is listed in the ingredients. I can say with near 100 percent certainty that you will see only the words turmeric or curcumin or turmeric extract (or powder) or curcumin extract (or powder). All the supplements with their ingredients listed this way will be priced at or below five dollars per bottle. On top of that, some branded turmeric or curcumin products are actually synthetics. Some supplement companies sell products honestly thinking they are using real turmeric when they are actually purchasing synthetic curcumin or turmeric and don’t even know it! The deception can seem insidious, but it’s not over yet.

When investigating your dietary supplements, always look for NSF (National Sanitation Foundation) and CGMP (current good manufacturing practice) certifications and a guarantee that the supplements have been formulated and packaged in registered ISO 22000 facilities only. These certifications establish strict guidelines that make sure the manufacturer follows ethical practices that all boil down to ensuring that the label matches the contents of the bottle. These certifications ensure compliance by requiring audits that verify that the company is meeting the highest standards of manufacturing and handling of products at all times.

I prefer to obtain a finished product directly from the company that owns the patents and ingredients instead of buying from third-party vendors — especially when it comes to turmeric, because of all the pitfalls I described above. Since the FDA does not regulate dietary supplements but only offers guidelines (which are not enforced until after an adverse report or event), many companies cheat their customers and increase their bottom line by blending patented ingredients with generic ones.

In essence, this means that they can state on their labels they are using the patented ingredients—like Curcumin C3 Complex — when in fact the product might contain only 5 percent to 10 percent Curcumin C3 Complex. The rest could be generic turmeric powder or even synthetic curcumin extracts. This practice is so widespread as to be epidemic. Consumer groups decry it, but federal agencies do not have the resources to investigate every supplement manufacturer.

Since I work closely with the manufacturers of the ingredients I use in my products, I know the raw cost of the product — that is, the actual price of the product before it is sold to wholesalers and then to retailers. Even nutrition companies that sell exclusively to healthcare providers and on the Internet join the many online discount vitamin companies (I like to call them the “big-box vitamin shops” or “discount warehouses” of supplements) that sell Curcumin C3 Complex at prices lower than the actual raw cost of the product.

No matter how much volume discount a company receives, the price of any product at retail should never be lower than the raw cost. Products sold below raw cost guarantee that the branded ingredient is being cut or diluted with generic or synthetic ingredients, or it contains other ingredients altogether. If you look at a patented ingredient and find a competitor with a price that is greatly lower or even half the price, you’re virtually guaranteed that the cheap product would not meet its label claims of potency or purity if tested.

Therefore, when looking for turmeric/curcumin — and, really, any other natural products — make sure they are:

  • Tested for heavy metals (there is a high risk of lead contamination in cheap supplements)
  • Produced in an NSF- and CGMP-certified facility
  • Manufactured in an ISO 22000-certified facility
  • Guaranteed for potency and purity, with documentation and third-party test results
  • Using patented ingredients (like Curcumin C3 Complex, for example) to ensure quality, potency, and purity
  • Certified GRAS (generally regarded as safe) by FDA

How much Curcumin C3 Complex should one take?

Now that you better understand the potential pitfalls of generic curcumin, I would like to talk about the product I know best and tell you how you can use it best to achieve your health and wellness goals.

Most of the clinical studies on the use of curcuminoids suggest a daily dose from 1 g (1,000 mg) to 3 g (3,000 mg), in divided doses for a better response (e.g., 1,000 mg three times a day). I recommend the divided doses because when curcumin is absorbed into the body, it has a short “peak” and then falls off over time. Therefore, multiple doses provide a better response throughout the day. The more chronic or severe the health condition, the higher the dose that the person would require. Some studies suggest upward of 8 g (8,000 mg) or more for severe, life-threatening diseases or end-stage cancers. [25]

When I first started recommending turmeric — and especially Curcumin C3 Complex — my patients were taking multiple pills three times daily, as there were no other options. That was one of the driving forces behind the development of Bosmeric-SR. I made sure we improved the efficacy of curcuminoids (through a combination of synergistic ingredients) and the potency of curcumin itself through a unique delivery system that requires just one to two caplets, twice daily with food. Those with severe health conditions, such as cancer, can take two caplets three times daily with food for twenty-four hours of full support.

Bosmeric-SR comes in an easy-to-swallow bilayered vegetarian caplet that has an immediate action — meaning it is designed to start working within 20 minutes (like a “fast tab”) but also incorporates sustained release for over eight hours of support. This specific type of sustained release provides the clinical benefits of 3 g (or more) of curcuminoids with the intake of just 1 g.

What about taking curcumin products during chemotherapy, radiation, or imaging (CT and PET scans)?

In the past, most oncologists and internal medicine physicians advised their patients not to take anything herbal while undergoing their chemotherapy and radiation treatments. Thankfully, this is now considered to be out-of-date advice.

Most recent studies (in vivo studies on various cancers) have shown that animals and human patients that took the combination of conventional treatment along with curcumin did better than those taking conventional treatment alone. Curcumin has been shown to have both chemo-protective and radio-protective benefits. [26] In other words, it helps protect the healthy cells from the damaging effects of chemotherapy and radiation. Thus, curcumin has a threefold effect:

  1. Curcumin reduces the toxic side effect of damage to healthy cells.
  2. Curcumin decreases inflammation and other dangerous cancer signals that aggravate cells (see figure Curcumin Targets).
  3. Curcumin sensitizes cancer cells to chemotherapy and radiation, which makes these toxic therapies more targeted (helping to attack the cancer, while leaving healthy, unaffected cells and tissues unharmed). [27]

Curcumin is only one means that might be able to improve someone’s treatment outcomes. Bosmeric-SR and all of its synergistic compounds may be an important part of an overall protocol for those suffering from cancer. The ingredients in Bosmeric-SR have not only healing aspects but also protective or preventative aspects. For that reason, I recommend all my patients take Bosmeric-SR for added radiation protection when they get CT and PET scans, and other imaging as well, including full-body scans at the airport.

For more detailed information on 10 steps to optimum health using diet and lifestyle changes and the use of natural anti-inflammatories, please read An Inflammation Nation.

Modified by permission from An Inflammation Nation by Sunil Pai © 2015.

Article Information
  1. A B Kunnumakkara, P Anand, and B B Aggarwal, “Curcumin Inhibits Proliferation, Invasion, Angiogenesis, and Metastasis of Different Cancers Through Interaction with Multiple Cell Signaling Proteins,” Cancer Lett 269, no. 2 (2008): 199–225, doi: 10.1016/j.canlet.2008.03.009.
  2. B Sayantan et al., “Curcumin and Tumor Immune-Editing: Resurrecting the Immune System,” Cell Div 10 (2015): 6, published online Oct 12, 2015, doi: 10.1186/s13008-015-0012-z.
  3. S Prasad et al., “Curcumin,” 1053–64.
Therapeutic Substance(s): 
Therapeutic intervention: 

DMSO

field_vote: 
Disease(s): 

Green Tea extract

field_vote: 

From www.cancertutor.com

TREATMENT RATING: This cancer treatment is rated ONLY as being effective on newly diagnosed cancer patients who do not have a fast-growing cancer and their cancer has not spread significantly. If you are an advanced cancer patient who has had a lot of chemotherapy, radiation or surgery or you have a potentially fast-growing cancer, do not use this treatment as your primary cancer treatment, use one of the protocols linked to on the following web page as your primary treatment:
Chapter on Natural Treatments For Advanced Cancer Patients

How It Works

Green Tea Polyphenols (GTP), particularly EGCG or EGCg (epigallocatechin gallate) not only inhibit an enzyme required for cancer cell growth, but also kills cancer cells with no ill effect on healthy cells. (1)

Green Tea

Dry green tea leaves are about 40 percent polyphenols by weight, and the most potent of these is EGCG. A team of scientists at Purdue University determined: “In the presence of EGCg, the cancer cells literally failed to grow or enlarge after division then presumably because they did not reach the minimum size needed to divide they underwent programmed cell death, or apoptosis.” EGCG, an antioxidant, is considered many times more potent than the Vitamin E or Vitamin C antioxidant properties. In a 1997 study, researchers from the University of Kansas determined that EGCG is twice as powerful as resveratrol, which itself is known to kill cancer cells (see the Grape Cure page).

Green Tea is also a key element of cancer prevention. (2) Researchers have known for years that the incidence of prostate cancer is considerably lower in Asian countries. One possible explanation advanced by scientists is the high consumption of plant foods among Asian populations. Another is the growing number of laboratory studies indicating that green tea — the most popular tea in China, Japan and other Asian countries — has anti-tumor effects.” (4)  Black tea is more popular in Western countries.

Worldwide, about 80 percent of the tea consumed is black tea. Both teas come from the same plant (Camellia sinensis). Black tea is fermented; green tea is not. Next to water, tea is the most widely consumed beverage in the world. Green tea contains more polyphenols — chemicals that act as powerful antioxidants and nontoxic, cancer preventive agents — than black tea. (3)  It has been speculated that the low lung cancer rate in Japan — despite the high rate of smoking — is due to green tea consumption.

Green Tea Vendor

Supercharging this Treatment

It would be a shame if someone went on a Green Tea treatment plan without also adding a few nutrients to make it a Dr. Rath Cellular Solution or Osiecki Cancer Technique treatment plan. Both of these treatment plans use Green Tea, but they add other nutrients that supercharge the Green Tea's ability to stop the spread of cancer cells.

This diet must be supplemented with treatments that kill cancer cells. Fortunately, green tea can be combined with virtually any other alternative treatment.

An alternative cancer treatment should be a complete treatment protocol. Do NOT forget to study the complete treatment protocol for Stage I, II and III cancer patients and the complete treatment protocol for Stage IV cancer patients:
Treatment For Stage I, II and III Cancer Patients
Treatment For Stage IV Cancer Patients

Site – Comments

  • GreenTea.com – Vendor and expert on green tea plants (grow your own green tea plants!!)
  • Chinese Food – Excellent Article
  • Green Teas – Excellent Article – Some technical information
Article Information
  1. http://www.dailymail.co.uk/health/article-2937811/How-green-tea-KILL-cancer-cells-Compound-destroys-disease-leaving-healthy-cells-unscathed.html
  2. http://preventcancer.aicr.org/site/PageServer?pagename=foodsthatfightcancer_green_tea
  3. http://umm.edu/health/medical/altmed/herb/green-tea
Therapeutic intervention: 

Resveratrol

field_vote: 

The Secrets of Resveratrol's Health Benefits

From www.drmercola.com
 

 

grapes, wine, resveratrolScientists have unraveled a mystery that has perplexed scientists since resveratrol, a chemical found in red wine and other foods, was first discovered to have health benefits: how does it control inflammation?

New research explains resveratrol's effect on inflammation, and also shows how it can be used to treat potentially deadly inflammatory disease, such as appendicitis, peritonitis, and systemic sepsis.

Resveratrol stops inflammation with a one-two punch that prevents your body from creating two different molecules known to trigger inflammation -- sphingosine kinase and phospholipase D.

 


Dr. Mercola's Comments:


Resveratrol is a potent antioxidant found in certain fruits, vegetables and cocoa that is emerging as a modern-day fountain of youth. The science surrounding this compound is so compelling that it has become one of my all-time favorite antioxidants, and I believe one that shows real promise of health benefits.

Resveratrol is typically associated with grapes and red wine, and was originally believed to be the reason for the so-called “French Paradox” -- the tendency for French people to have great cardiovascular health despite a “poor” diet and love for wine.

This newest study reveals one way in which resveratrol helps to protect your health, and that is by preventing your body from sphingosine kinase and phospholipase D -- two molecules known to trigger inflammation.

While inflammation is a natural response in your body (it’s a process in which your body’s white blood cells protect you from outside invaders such as bacteria and viruses), it’s possible for your body to exist in a chronically inflamed state.

Chronic inflammation is not a beneficial bodily response, and in fact has been linked to numerous chronic diseases including heart disease.

What Makes Resveratrol a Unique Antioxidant

Resveratrol is unique among antioxidants because it can cross the blood-brain barrier to help protect your brain and nervous system, and studies show that its benefits are wide reaching, including:

• Protecting your cells from free radical damage

• Inhibiting the spread of cancer, especially prostate cancer

• Lowering your blood pressure

• Keeping your heart healthy and improving elasticity in your blood vessels

• Normalizing your anti-inflammatory response

• Helping to prevent Alzheimer’s disease

Because resveratrol appears to be so effective at warding off many diseases associated with aging, it is often referred to a “fountain of youth” that can extend lifespan.

Already, animal studies have shown that resveratrol helped overweight mice run farther and live about 20 percent longer. It has even been found to increase the lifespan of human cells.

Resveratrol also seems to produce many similar benefits as exercise, and I suspect it would be a powerful addition to exercise. I personally take resveratrol because of this belief.

The Best Sources of Resveratrol

Resveratrol is found in grapes, which produce it as a defense against fungi. Muscadine grapes actually have the highest concentration of resveratrol in nature because of their extra thick skins and numerous seeds where it is concentrated.

Resveratrol is also found in abundance in red wine, and it’s highly soluble in alcohol, meaning your body may absorb more of it from red wine than from other sources. But there ARE other sources out there, including cocoa, dark chocolate and peanuts.

If you opt to take a resveratrol supplement, there are numerous products on the market. Be sure to look for one made from muscadine grapes that uses WHOLE grape skins and seeds, as this is where many of the benefits are concentrated.

Therapeutic Substance(s): 
Therapeutic intervention: 
Disease(s): 

Photodynamic Therapy

field_vote: 

Photodynamic therapy

From Wikipedia, the free encyclopedia

Photodynamic therapy (PDT), sometimes called photochemotherapy, is a form of phototherapy involving light and a photosensitizing chemical substance, used in conjunction with molecular oxygen to elicit cell death (phototoxicity). PDT has proven ability to kill microbial cells, including bacteria, fungi and viruses.[1] PDT is popularly used in treating acne. It is used clinically to treat a wide range of medical conditions, including wet age-related macular degeneration, psoriasis, atherosclerosis and has shown some efficacy in anti-viral treatments, including herpes. It also treats malignant cancers[2] including head and neck, lung, bladder and particular skin. The technology has also been tested for treatment of prostate cancer, both in a dog model[3] and in prostate cancer patients.[4]

It is recognised as a treatment strategy that is both minimally invasive and minimally toxic. Other light-based and laser therapies such as laser wound healing and rejuvenation, or intense pulsed light hair removal do not require a photosensitizer.[5] Photosensitisers have been employed to sterilise blood plasma and water in order to remove blood-borne viruses and microbes and have been considered for agricultural uses, including herbicides and insecticides.

Photodynamic therapy's advantages lessen the need for delicate surgery and lengthy recuperation and minimal formation of scar tissue and disfigurement. A side effect is the associated photosensitisation of skin tissue.[5]

Contents

Basics

PDT applications involve three components:[2] a photosensitizer, a light source and tissue oxygen. The wavelength of the light source needs to be appropriate for exciting the photosensitizer to produce radicals and/or reactive oxygen species. These are free radicals (Type I) generated through electron abstraction or transfer from a substrate molecule and highly reactive state of oxygen known as singlet oxygen (Type II).

PDT is a multi-stage process. First a photosensitiser with negligible dark toxicity is administered, either systemically or topically, in the absence of light. When a sufficient amount of photosensitiser appears in diseased tissue, the photosensitiser is activated by exposure to light for a specified period. The light dose supplies sufficient energy to stimulate the photosensitiser, but not enough to damage neighbouring healthy tissue. The reactive oxygen kills the target cells.[5]

Photochemical processes

When a photosensitiser is in its excited state (3Psen*) it can interact with molecular triplet oxygen (3O2) and produce radicals and reactive oxygen species (ROS), crucial to the Type II mechanism. These species include singlet oxygen (1O2), hydroxyl radicals (•OH) and superoxide (O2−) ions. They can interact with cellular components including unsaturated lipids, amino acid residues and nucleic acids. If sufficient oxidative damage ensues, this will result in target-cell death (only within the illuminated area).[5]

Photochemical mechanisms

When a chromophore molecule, such as a cyclic tetrapyrrolic molecule, absorbs a photon, one of its electrons is promoted into a higher-energy orbital, elevating the chromophore from the ground state (S0) into a short-lived, electronically excited state (Sn) composed of vibrational sub-levels (Sn′). The excited chromophore can lose energy by rapidly decaying through these sub-levels via internal conversion (IC) to populate the first excited singlet state (S1), before quickly relaxing back to the ground state.[5]

The decay from the excited singlet state (S1) to the ground state (S0) is via fluorescence (S1 → S0). Singlet state lifetimes of excited fluorophores are very short (τfl. = 10−9–10−6 seconds) since transitions between the same spin states (S → S or T → T) conserve the spin multiplicity of the electron and, according to the Spin Selection Rules, are therefore considered "allowed" transitions. Alternatively, an excited singlet state electron (S1) can undergo spin inversion and populate the lower-energy first excited triplet state (T1) via intersystem crossing (ISC); a spin-forbidden process, since the spin of the electron is no longer conserved. The excited electron can then undergo a second spin-forbidden inversion and depopulate the excited triplet state (T1) by decaying to the ground state (S0) via phosphorescence (T1→ S0). Owing to the spin-forbidden triplet to singlet transition, the lifetime of phosphorescence (τP = 10−3 − 1 second) is considerably longer than that of fluorescence.[5]

Photosensitisers and photochemistry

Tetrapyrrolic photosensitisers in the excited singlet state (1Psen*, S>0) are relatively efficient at intersystem crossing and can consequently have a high triplet-state quantum yield. The longer lifetime of this species is sufficient to allow the excited triplet state photosensitiser to interact with surrounding bio-molecules, including cell membrane constituents.[5]

Photochemical reactions

Excited triplet-state photosensitisers can react via Type-I and Type-II processes. Type-I processes can involve the excited singlet or triplet photosensitiser (1Psen*, S1; 3Psen*, T1), however due to the short lifetime of the excited singlet state, the photosensitiser can only react if it is intimately associated with a substrate. In both cases the interaction is with readily oxidisable or reducible substrates. Type-II processes involve the direct interaction of the excited triplet photosensitiser (3Psen*, T1) with molecular oxygen (3O2, 3Σg).[5]

Type-I processes

Type-I processes can be divided into Type I(i) and Type I(ii). Type I (i) involves the transfer of an electron (oxidation) from a substrate molecule to the excited state photosensitiser (Psen*), generating a photosensitiser radical anion (Psen•−) and a substrate radical cation (Subs•+). The majority of the radicals produced from Type-I(i) reactions react instantaneously with oxygen, generating a mixture of oxygen intermediates. For example, the photosensitiser radical anion can react instantaneously with molecular oxygen (3O2) to generate a superoxide radical anion (O2•−), which can go on to produce the highly reactive hydroxyl radical (OH•), initiating a cascade of cytotoxic free radicals; this process is common in the oxidative damage of fatty acids and other lipids.[5]

The Type-I process (ii) involves the transfer of a hydrogen atom (reduction) to the excited state photosensitiser (Psen*). This generates free radicals capable of rapidly reacting with molecular oxygen and creating a complex mixture of reactive oxygen intermediates, including reactive peroxides.[5]

Type-II processes

Type-II processes involve the direct interaction of the excited triplet state photosensitiser (3Psen*) with ground state molecular oxygen (3O2, 3Σg); a spin allowed transition—the excited state photosensitiser and ground state molecular oxygen are of the same spin state (T).[5]

When the excited photosensitiser collides with molecular oxygen, a process of triplet-triplet annihilation takes place (3Psen* 1Psen and 3O2 1O2). This inverts the spin of one oxygen molecule's (3O2) outermost antibonding electrons, generating two forms of singlet oxygen (1Δg and 1Σg), while simultaneously depopulating the photosensitiser's excited triplet state (T1 → S0). The higher-energy singlet oxygen state (1Σg, 157kJ mol−1 > 3Σg) is very short-lived (1Σg ≤ 0.33 milliseconds (methanol), undetectable in H2O/D2O) and rapidly relaxes to the lower-energy excited state (1Δg, 94kJ mol−1 > 3Σg). It is, therefore, this lower-energy form of singlet oxygen (1Δg) that is implicated in cell injury and cell death.[5]

The highly-reactive oxygen species (1O2) produced via the Type-II process act near to their site generation and within a radius of approximately 20 nm, with a typical lifetime of approximately 40 nanoseconds in biological systems.[5]

It is possible that (over a 6 μs period) singlet oxygen can diffuse up to approximately 300 nm in vivo. Singlet oxygen can theoretically only interact with proximal molecules and structures within this radius. ROS initiate reactions with many biomolecules, including amino acid residues in proteins, such as tryptophan; unsaturated lipids like cholesterol and nucleic acid bases, particularly guanosine and guanine derivatives, with the latter base more susceptible to ROS. These interactions cause damage and potential destruction to cellular membranes and enzyme deactivation, culminating in cell death.[5]

It is probable that in the presence of molecular oxygen and as a direct result of the photoirradiation of the photosensitiser molecule, both Type-I and II pathways play a pivotal role in disrupting cellular mechanisms and cellular structure. Nevertheless, considerable evidence suggests that the Type-II photo-oxygenation process predominates in the induction of cell damage, a consequence of the interaction between the irradiated photosensitiser and molecular oxygen. Cells in vivo may be partially protected against the effects of photodynamic therapy by the presence of singlet oxygen scavengers (such as histidine). Certain skin cells are somewhat resistant to PDT in the absence of molecular oxygen; further supporting the proposal that the Type-II process is at the heart of photoinitiated cell death.[5]

The efficiency of Type-II processes is dependent upon the triplet state lifetime τT and the triplet quantum yield (ΦT) of the photosensitiser. Both of these parameters have been implicated in phototherapeutic effectiveness; further supporting the distinction between Type-I and Type-II mechanisms. However, the success of a photosensitiser is not exclusively dependent upon a Type-II process. Multiple photosensitisers display excited triplet lifetimes that are too short to permit a Type-II process to occur. For example, the copper metallated octaethylbenzochlorin photosensitiser has a triplet state lifetime of less than 20 nanoseconds and is still deemed to be an efficient photodynamic agent.[5]

Reactive oxygen species

In air and tissue, molecular oxygen occurs in a triplet state, whereas almost all other molecules are in a singlet state. Reactions between triplet and singlet molecules are forbidden by quantum mechanics, making oxygen relatively non-reactive at physiological conditions. A photosensitizer is a chemical compound that can be promoted to an excited state upon absorption of light and undergo intersystem crossing (ISC) with oxygen to produce singlet oxygen. This species is highly cytotoxic, rapidly attacking any organic compounds it encounters. It is rapidly eliminated from cells, in an average of 3 µs.[6]

Photosensitisers

Many photosensitizers for PDT exist. They divide into porphyrins, chlorophylls and dyes.[7] Examples include aminolevulinic acid (ALA), Silicon Phthalocyanine Pc 4, m-tetrahydroxyphenylchlorin (mTHPC) and mono-L-aspartyl chlorin e6 (NPe6).

Photosensitizers commercially available for clinical use include Allumera, Photofrin, Visudyne, Levulan, Foscan, Metvix, Hexvix, Cysview and Laserphyrin, with others in development, e.g. Antrin, Photochlor, Photosens, Photrex, Lumacan, Cevira, Visonac, BF-200 ALA,[7][8] Amphinex[9] and Azadipyrromethenes.

The major difference between photosensitizers is the parts of the cell that they target. Unlike in radiation therapy, where damage is done by targeting cell DNA, most photosensitizers target other cell structures. For example, mTHPC localizes in the nuclear envelope.[10] In contrast, ALA localizes in the mitochondria[11] and methylene blue in the lysosomes.[12]

Cyclic tetrapyrrolic chromophores

Cyclic tetrapyrrolic molecules are fluorophores and photosensitisers. Cyclic tetrapyrrolic derivatives have an inherent similarity to the naturally occurring porphyrins present in living matter—consequently they have little or no toxicity in the absence of light.

Porphyrins

Porphyrins are a group of naturally occurring and intensely coloured compounds, whose name is drawn from the Greek word porphura, or purple. These molecules perform biologically important roles, including oxygen transport and photosynthesis and have applications in fields ranging from fluorescent imaging to medicine. Porphyrins are tetrapyrrolic molecules, with the heart of the skeleton a heterocyclic macrocycle, known as a porphine. The fundamental porphine frame consists of four pyrrolic sub-units linked on opposing sides (α-positions, numbered 1, 4, 6, 9, 11, 14, 16 and 19) through four methine (CH) bridges (5, 10, 15 and 20), known as the meso-carbon atoms/positions. The resulting conjugated planar macrocycle may be substituted at the meso- and/or β-positions (2, 3, 7, 8, 12, 13, 17 and 18): if the meso- and β-hydrogens are substituted with non-hydrogen atoms or groups, the resulting compounds are known as porphyrins.[5]

The inner two protons of a free-base porphyrin can be removed by strong bases such as alkoxides, forming a dianionic molecule; conversely, the inner two pyrrolenine nitrogens can be protonated with acids such as trifluoroacetic acid affording a dicationic intermediate. The tetradentate anionic species can readily form complexes with most metals.[5]

Absorption spectroscopy

Porphyrin's highly conjugated skeleton produces a characteristic ultra-violet visible (UV-VIS) spectrum. The spectrum typically consists of an intense, narrow absorption band (ε > 200000 l mol−1 cm−1) at around 400 nm, known as the Soret or B band, followed by four longer wavelength (450–700 nm), weaker absorptions (ε > 20000 l mol−1 cm−1 (free-base porphyrins)) referred to as the Q bands.

The Soret band arises from a strong electronic transition from the ground state to the second excited singlet state (S0 → S2); whereas the Q band is a result of a weak transition to the first excited singlet state (S0 → S1). The dissipation of energy via internal conversion (IC) is so rapid that fluorescence is only observed from depopulation of the first excited singlet state to the lower-energy ground state (S1 → S0).[5]

Ideal photosensitisers

The key characteristic of a photosensitiser is the ability to preferentially accumulate in diseased tissue and induce a desired biological effect via the generation of cytotoxic species. Specific criteria:[13]

  • Strong absorption with a high extinction coefficient in the red/near infrared region of the electromagnetic spectrum (600–850 nm)—allows deeper tissue penetration. (Tissue is much more transparent at longer wavelengths (~700–850 nm). Longer wavelengths allow the light to penetrate deeper[9] and treat larger structures.)[9]
  • Suitable photophysical characteristics: a high-quantum yield of triplet formation (ΦT ≥ 0.5); a high singlet oxygen quantum yield (ΦΔ ≥ 0.5); a relatively long triplet state lifetime (τT, μs range); and a high triplet-state energy (≥ 94 kJ mol−1). Values of ΦT= 0.83 and ΦΔ = 0.65 (haematoporphyrin); ΦT = 0.83 and ΦΔ = 0.72 (etiopurpurin); and ΦT = 0.96 and ΦΔ = 0.82 (tin etiopurpurin) have been achieved
  • Low dark toxicity and negligible cytotoxicity in the absence of light. (The photosensitizer should not be harmful to the target tissue until the treatment beam is applied.)
  • Preferential accumulation in diseased/target tissue over healthy tissue
  • Rapid clearance from the body post-procedure
  • High chemical stability: single, well-characterised compounds, with a known and constant composition
  • Short and high-yielding synthetic route (with easy translation into multi-gram scales/reactions)
  • Simple and stable formulation
  • Soluble in biological media, allowing intravenous administration. Otherwise, a hydrophilic delivery system must enable efficient and effective transportation of the photosensitiser to the target site via the bloodstream.
  • Low photobleaching to prevent degradation of the photosensitizer so it can continue producing singlet oxygen
  • Natural fluorescence (Many optical dosimetry techniques, such as fluorescence spectroscopy, depend on fluorescence.)[14]

First generation

While the disadvantages associated with first generation photosensitisers HpD and Photofrin (skin sensitivity and weak absorption at 630 nm) permitted some therapeutic use, they markedly reduced application to a wider field of disease. Second generation photosensitisers were key to the development of photodynamic therapy.[5]

Second generation

5-Aminolaevulinic acid

5-Aminolaevulinic acid (ALA) is a prodrug used to treat and image multiple superficial cancers and tumours. ALA a key precursor in the biosynthesis of the naturally occurring porphyrin, haem.[5]

Haem is synthesised in every energy-producing cell in the body and is a key structural component of haemoglobin, myoglobin and other haemproteins. The immediate precursor to haem is protoporphyrin IX (PPIX), an effective photosensitiser. Haem itself is not a photosensitiser, due to the coordination of a paramagnetic ion in the centre of the macrocycle, causing significant reduction in excited state lifetimes.[5]

The haem molecule is synthesised from glycine and succinyl coenzyme A (succinyl CoA). The rate-limiting step in the biosynthesis pathway is controlled by a tight (negative) feedback mechanism in which the concentration of haem regulates the production of ALA. However, this controlled feedback can be by-passed by artificially adding excess exogenous ALA to cells. The cells respond by producing PPIX (photosensitiser) at a faster rate than the ferrochelatase enzyme can convert it to haem.[5]

ALA, marketed as Levulan, has shown promise in photodynamic therapy (tumours) via both intravenous and oral administration, as well as through topical administration in the treatment of malignant and non-malignant dermatological conditions, including psoriasis, Bowen's disease and Hirsutism (Phase II/III clinical trials).[5]

ALA accumulates more rapidly in comparison to other intravenously administered sensitisers. Typical peak tumour accumulation levels post-administration for PPIX are usually achieved within several hours; other (intravenous) photosensitisers may take up to 96 hours to reach peak levels. ALA is also excreted more rapidly from the body (∼24 hours) than other photosensitisers, minimising photosensitivity side effects.[5]

Esterified ALA derivatives with improved bioavailability have been examined. A methyl ALA ester (Metvix) is now available for basal cell carcinoma and other skin lesions. Benzyl (Benvix) and hexyl ester (Hexvix) derivatives are used for gastrointestinal cancers and for the diagnosis of bladder cancer.[5]

Verteporfin

Benzoporphyrin derivative monoacid ring A (BPD-MA) marketed as Visudyne (Verteporfin, for injection) has been approved by health authorities in multiple jurisdictions, including US FDA, for the treatment of wet AMD beginning in 1999. It has also undergone Phase III clinical trials (USA) for the treatment of cutaneous non-melanoma skin cancer.[5]

The chromophore of BPD-MA has a red-shifted and intensified long-wavelength absorption maxima at approximately 690 nm. Tissue penetration by light at this wavelength is 50% greater than that achieved for Photofrin (λmax. = 630 nm).[5]

Verteporfin has further advantages over the first generation sensitiser Photofrin. It is rapidly absorbed by the tumour (optimal tumour-normal tissue ratio 30–150 minutes post-intravenous injection) and is rapidly cleared from the body, minimising patient photosensitivity (1–2 days).[5]

Purlytin

Chlorin photosensitiser tin etiopurpurin is marketed as Purlytin. Purlytin has undergone Phase II clinical trials for cutaneous metastatic breast cancer and Kaposi's sarcoma in patients with AIDS (acquired immunodeficiency syndrome). Purlytin has been used successfully to treat the non-malignant conditions psoriasis and restenosis.[5]

Chlorins are distinguished from the parent porphyrins by a reduced exocyclic double bond, decreasing the symmetry of the conjugated macrocycle. This leads to increased absorption in the long-wavelength portion of the visible region of the electromagnetic spectrum (650–680 nm). Purlytin is a purpurin; a degradation product of chlorophyll.[5]

Purlytin has a tin atom chelated in its central cavity that causes a red-shift of approximately 20–30 nm (with respect to Photofrin and non-metallated etiopurpurin, λmax.SnEt2 = 650 nm). Purlytin has been reported to localise in skin and produce a photoreaction 7–14 days post-administration.[5]

Foscan

Tetra(m-hydroxyphenyl)chlorin (mTHPC) is in clinical trials for head and neck cancers under the trade name Foscan. It has also been investigated in clinical trials for gastric and pancreatic cancers, hyperplasia, field sterilisation after cancer surgery and for the control of antibiotic-resistant bacteria.[5]

Foscan has a singlet oxygen quantum yield comparable to other chlorin photosensitisers but lower drug and light doses (approximately 100 times more photoactive than Photofrin).[5]

Foscan can render patients photosensitive for up to 20 days after initial illumination.[5]

Lutex

Lutetium texaphyrin, marketed under the trade name Lutex and Lutrin, is a large porphyrin molecule. Texaphyrins are expanded porphyrins that have a penta-aza core. It offers strong absorption in the 730–770 nm region. Tissue transparency is optimal in this range. As a result, Lutex-based PDT can (potentially) be carried out more effectively at greater depths and on larger tumours.[5]

Lutex has entered Phase II clinical trials for evaluation against breast cancer and malignant melanomas.[5]

A Lutex derivative, Antrin, has undergone Phase I clinical trials for the prevention of restenosis of vessels after cardiac angioplasty by photoinactivating foam cells that accumulate within arteriolar plaques. A second Lutex derivative, Optrin, is in Phase I trials for AMD.[5]

Texaphyrins also have potential as radiosensitisers (Xcytrin) and chemosensitisers. Xcytrin, a gadolinium texaphyrin (motexafin gadolinium), has been evaluated in Phase III clinical trials against brain metastases and Phase I clinical trials for primary brain tumours.[5]

ATMPn

9-Acetoxy-2,7,12,17-tetrakis-(β-methoxyethyl)-porphycene has been evaluated as an agent for dermatological applications against psoriasis vulgaris and superficial non-melanoma skin cancer.[5]

Zinc phthalocyanine

A liposomal formulation of zinc phthalocyanine (CGP55847) has undergone clinical trials (Phase I/II, Switzerland) against squamous cell carcinomas of the upper aerodigestive tract. Phthalocyanines (PCs) are related to tetra-aza porphyrins. Instead of four bridging carbon atoms at the meso-positions, as for the porphyrins, PCs have four nitrogen atoms linking the pyrrolic sub-units. PCs also have an extended conjugate pathway: a benzene ring is fused to the β-positions of each of the four-pyrrolic sub-units. These rings strengthen the absorption of the chromophore at longer wavelengths (with respect to porphyrins). The absorption band of PCs is almost two orders of magnitude stronger than the highest Q band of haematoporphyrin. These favourable characteristics, along with the ability to selectively functionalise their peripheral structure, make PCs favourable photosensitiser candidates.[5]

A sulphonated aluminium PC derivative (Photosense) has entered clinical trials (Russia) against skin, breast and lung malignancies and cancer of the gastrointestinal tract. Sulphonation significantly increases PC solubility in polar solvents including water, circumventing the need for alternative delivery vehicles.[5]

PC4 is a silicon complex under investigation for the sterilisation of blood components against human colon, breast and ovarian cancers and against glioma.[5]

A shortcoming of many of the metallo-PCs is their tendency to aggregate in aqueous buffer (pH 7.4), resulting in a decrease, or total loss, of their photochemical activity. This behaviour can be minimised in the presence of detergents.[5]

Metallated cationic porphyrazines (PZ), including PdPZ+, CuPZ+, CdPZ+, MgPZ+, AlPZ+ and GaPZ+, have been tested in vitro on V-79 (Chinese hamster lung fibroblast) cells. These photosensitisers display substantial dark toxicity.[5]

Naphthalocyanines

Naphthalocyanines (NCs) are an extended PC derivative. They have an additional benzene ring attached to each isoindole sub-unit on the periphery of the PC structure. Subsequently, NCs absorb strongly at even longer wavelengths (approximately 740–780 nm) than PCs (670–780 nm). This absorption in the near infrared region makes NCs candidates for highly pigmented tumours, including melanomas, which present significant absorption problems for visible light.[5]

However, problems associated with NC photosensitisers include lower stability, as they decompose in the presence of light and oxygen. Metallo-NCs, which lack axial ligands, have a tendency to form H-aggregates in solution. These aggregates are photoinactive, thus compromising the photodynamic efficacy of NCs.[5]

Silicon naphthalocyanine attached to copolymer PEG-PCL (poly(ethylene glycol)-block-poly(ε-caprolactone)) accumulates selectively in cancer cells and reaches a maximum concentration after about one day. The compound provides real time near-infrared (NIR) fluorescence imaging with an extinction coefficient of 2.8 × 105 M−1 cm−1 and combinatorial phototherapy with dual photothermal and photodynamic therapeutic mechanisms that may be appropriate for adriamycin-resistant tumors. The particles had a hydrodynamic size of 37.66 ± 0.26 nm (polydispersity index = 0.06) and surface charge of −2.76 ± 1.83 mV.[15]

Functional groups

Altering the peripheral functionality of porphyrin-type chromophores can affect photodynamic activity.[5]

Diamino platinum porphyrins show high anti-tumour activity, demonstrating the combined effect of the cytotoxicity of the platinum complex and the photodynamic activity of the porphyrin species.[5]

Positively charged PC derivatives have been investigated. Cationic species are believed to selectively localise in the mitochondria.[5]

Zinc and copper cationic derivatives have been investigated. The positively charged zinc complexed PC is less photodynamically active than its neutral counterpart in vitro against V-79 cells.[5]

Water-soluble cationic porphyrins bearing nitrophenyl, aminophenyl, hydroxyphenyl and/or pyridiniumyl functional groups exhibit varying cytotoxicity to cancer cells in vitro, depending on the nature of the metal ion (Mn, Fe, Zn, Ni) and on the number and type of functional groups. The manganese pyridiniumyl derivative has shown the highest photodynamic activity, while the nickel analogue is photoinactive.[5]

Another metallo-porphyrin complex, the iron chelate, is more photoactive (towards HIV and simian immunodeficiency virus in MT-4 cells) than the manganese complexes; the zinc derivative is photoinactive.[5]

The hydrophilic sulphonated porphyrins and PCs (AlPorphyrin and AlPC) compounds were tested for photodynamic activity. The disulphonated analogues (with adjacent substituted sulphonated groups) exhibited greater photodynamic activity than their di-(symmetrical), mono-, tri- and tetra-sulphonated counterparts; tumour activity increased with increasing degree of sulphonation.[5]

Third generation

Many photosensitisers are poorly soluble in aqueous media, particularly at physiological pH, limiting their use.[5]

Alternate delivery strategies range from the use of oil-in-water (o/w) emulsions to carrier vehicles such as liposomes and nanoparticles. Although these systems may increase therapeutic effects, the carrier system may inadvertently decrease the "observed" singlet oxygen quantum yield (ΦΔ): the singlet oxygen generated by the photosensitiser must diffuse out of the carrier system; and since singlet oxygen is believed to have a narrow radius of action, it may not reach the target cells. The carrier may limit light absorption, reducing singlet oxygen yield.[5]

Another alternative that does not display the scattering problem is the use of moieties. Strategies include directly attaching photosensitisers to biologically active molecules such as antibodies.[5]

Metallation

Various metals form into complexes with photosensitiser macrocycles. Multiple second generation photosensitisers contain a chelated central metal ion. The main candidates are transition metals, although photosensitisers co-ordinated to group 13 (Al, AlPcS4) and group 14 (Si, SiNC and Sn, SnEt2) metals have been synthesised.[5]

The metal ion does not confer definite photoactivity on the complex. Copper (II), cobalt (II), iron (II) and zinc (II) complexes of Hp are all photoinactive in contrast to metal-free porphyrins. However, texaphyrin and PC photosensitisers do not contain metals; only the metallo-complexes have demonstrated efficient photosensitisation.[5]

The central metal ion, bound by a number of photosensitisers, strongly influences the photophysical properties of the photosensitiser. Chelation of paramagnetic metals to a PC chromophore appears to shorten triplet lifetimes (down to nanosecond range), generating variations in the triplet quantum yield and triplet lifetime of the photoexcited triplet state.[5]

Certain heavy metals are known to enhance inter-system crossing (ISC). Generally, diamagnetic metals promote ISC and have a long triplet lifetime. In contrast, paramagnetic species deactivate excited states, reducing the excited-state lifetime and preventing photochemical reactions. However, exceptions to this generalisation include copper octaethylbenzochlorin.[5]

Many metallated paramagnetic texaphyrin species exhibit triplet-state lifetimes in the nanosecond range. These results are mirrored by metallated PCs. PCs metallated with diamagnetic ions, such as Zn2+, Al3+ and Ga3+, generally yield photosensitisers with desirable quantum yields and lifetimes (ΦT 0.56, 0.50 and 0.34 and τT 187, 126 and 35 μs, respectively). Photosensitiser ZnPcS4 has a singlet oxygen quantum yield of 0.70; nearly twice that of most other mPCs (ΦΔ at least 0.40).[5]

Expanded metallo-porphyrins

Expanded porphyrins have a larger central binding cavity, increasing the range of potential metals.[5]

Diamagnetic metallo-texaphyrins have shown photophysical properties; high triplet quantum yields and efficient generation of singlet oxygen. In particular, the zinc and cadmium derivatives display triplet quantum yields close to unity. In contrast, the paramagnetic metallo-texaphyrins, Mn-Tex, Sm-Tex and Eu-Tex, have undetectable triplet quantum yields. This behaviour is parallel with that observed for the corresponding metallo-porphyrins.[5]

The cadmium-texaphyrin derivative has shown in vitro photodynamic activity against human leukemia cells and Gram positive (Staphylococcus) and Gram negative (Escherichia coli) bacteria. Although follow-up studies have been limited with this photosensitiser due to the toxicity of the complexed cadmium ion.[5]

A zinc-metallated seco-porphyrazine has a high quantum singlet oxygen yield (ΦΔ 0.74). This expanded porphyrin-like photosensitiser has shown the best singlet oxygen photosensitising ability of any of the reported seco-porphyrazines. Platinum and palladium derivatives have been synthesised with singlet oxygen quantum yields of 0.59 and 0.54, respectively.[5]

Metallochlorins/bacteriochlorins

The tin (IV) purpurins are more active when compared with analogous zinc (II) purpurins, against human cancers.[5]

Sulphonated benzochlorin derivatives demonstrated a reduced phototherapeutic response against murine leukemia L1210 cells in vitro and transplanted urothelial cell carcinoma in rats, whereas the tin (IV) metallated benzochlorins exhibited an increased photodynamic effect in the same tumour model.[5]

Copper octaethylbenzochlorin demonstrated greater photoactivity towards leukemia cells in vitro and a rat bladder tumour model. It may derive from interactions between the cationic iminium group and biomolecules. Such interactions may allow electron-transfer reactions to take place via the short-lived excited singlet state and lead to the formation of radicals and radical ions. The copper-free derivative exhibited a tumour response with short intervals between drug administration and photodynamic activity. Increased in vivo activity was observed with the zinc benzochlorin analogue.[5]

Metallo-phthalocyanines

PCs properties are strongly influenced by the central metal ion. Co-ordination of transition metal ions gives metallo-complexes with short triplet lifetimes (nanosecond range), resulting in different triplet quantum yields and lifetimes (with respect to the non-metallated analogues). Diamagnetic metals such as zinc, aluminium and gallium, generate metallo-phthalocyanines (MPC) with high triplet quantum yields (ΦT ≥ 0.4) and short lifetimes (ZnPCS4 τT = 490 Fs and AlPcS4 τT = 400 Fs) and high singlet oxygen quantum yields (ΦΔ ≥ 0.7). As a result, ZnPc and AlPc have been evaluated as second generation photosensitisers active against certain tumours.[5]

Metallo-naphthocyaninesulfobenzo-porphyrazines (M-NSBP)

Aluminium has been successfully coordinated to M-NSBP. The resulting complex showed photodynamic activity against EMT-6 tumour-bearing Balb/c mice (disulphonated analogue demonstrated greater photoactivity than the mono-derivative).[5]

Metallo-naphthalocyanines

Work with zinc NC with various amido substituents revealed that the best phototherapeutic response (Lewis lung carcinoma in mice) with a tetrabenzamido analogue. Complexes of silicon (IV) NCs with two axial ligands in anticipation the ligands minimise aggregation. Disubstituted analogues as potential photodynamic agents (a siloxane NC substituted with two methoxyethyleneglycol ligands) are an efficient photosensitiser against Lewis lung carcinoma in mice. SiNC[OSi(i-Bu)2-n-C18H37]2 is effective against Balb/c mice MS-2 fibrosarcoma cells.Siloxane NCs may be efficacious photosensitisers against EMT-6 tumours in Balb/c mice. The ability of metallo-NC derivatives (AlNc) to generate singlet oxygen is weaker than the analogous (sulphonated) metallo-PCs (AlPC); reportedly 1.6–3 orders of magnitude less.[5]

In porphyrin systems, the zinc ion appears to hinder the photodynamic activity of the compound. By contrast, in the higher/expanded π-systems, zinc-chelated dyes form complexes with good to high results.[5]

An extensive study of metallated texaphyrins focused on the lanthanide (III) metal ions, Y, In, Lu, Cd, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm and Yb found that when diamagnetic Lu (III) was complexed to texaphyrin, an effective photosensitiser (Lutex) was generated. However, using the paramagnetic Gd (III) ion for the Lu metal, exhibited no photodynamic activity. The study found a correlation between the excited-singlet and triplet state lifetimes and the rate of ISC of the diamagnetic texaphyrin complexes, Y(III), In (III) and Lu (III) and the atomic number of the cation.[5]

Paramagnetic metallo-texaphyrins displayed rapid ISC. Triplet lifetimes were strongly affected by the choice of metal ion. The diamagnetic ions (Y, In and Lu) displayed triplet lifetimes ranging from 187, 126 and 35 μs, respectively. Comparable lifetimes for the paramagnetic species (Eu-Tex 6.98 μs, Gd-Tex 1.11, Tb-Tex < 0.2, Dy-Tex 0.44 × 10−3, Ho-Tex 0.85 × 10−3, Er-Tex 0.76 × 10−3, Tm-Tex 0.12 × 10−3 and Yb-Tex 0.46) were obtained.[5]

Three measured paramagnetic complexes measured significantly lower than the diamagnetic metallo-texaphyrins.[5]

In general, singlet oxygen quantum yields closely followed the triplet quantum yields.[5]

Various diamagnetic and paramagnetic texaphyrins investigated have independent photophysical behaviour with respect to a complex's magnetism. The diamagnetic complexes were characterised by relatively high fluorescence quantum yields, excited-singlet and triplet lifetimes and singlet oxygen quantum yields; in distinct contrast to the paramagnetic species.[5]

The +2 charged diamagnetic species appeared to exhibit a direct relationship between their fluorescence quantum yields, excited state lifetimes, rate of ISC and the atomic number of the metal ion. The greatest diamagnetic ISC rate was observed for Lu-Tex; a result ascribed to the heavy atom effect. The heavy atom effect also held for the Y-Tex, In-Tex and Lu-Tex triplet quantum yields and lifetimes. The triplet quantum yields and lifetimes both decreased with increasing atomic number. The singlet oxygen quantum yield correlated with this observation.

Photophysical properties displayed by paramagnetic species were more complex. The observed data/behaviour was not correlated with the number of unpaired electrons located on the metal ion. For example:

  • ISC rates and the fluorescence lifetimes gradually decreased with increasing atomic number.
  • Gd-Tex and Tb-Tex chromophores showed (despite more unpaired electrons) slower rates of ISC and longer lifetimes than Ho-Tex or Dy-Tex.

To achieve selective target cell destruction, while protecting normal tissues, either the photosensitizer can be applied locally to the target area, or targets can be locally illuminated. Skin conditions, including acne, psoriasis and also skin cancers, can be treated topically and locally illuminated. For internal tissues and cancers, intravenously administered photosensitizers can be illuminated using endoscopes and fiber optic catheters.[citation needed]

Photosensitizers can target viral and microbial species, including HIV and MRSA.[16] Using PDT, pathogens present in samples of blood and bone marrow can be decontaminated before the samples are used further for transfusions or transplants.[17] PDT can also eradicate a wide variety of pathogens of the skin and of the oral cavities. Given the seriousness that drug resistant pathogens have now become, there is increasing research into PDT as a new antimicrobial therapy.[18]

Applications

Vascular targeting

Some photosensitisers naturally accumulate in the endothelial cells of vascular tissue allowing 'vascular targeted' PDT.

Verteporfin was shown to target the neovasculature resulting from macular degeneration in the macula within the first thirty minutes after intravenous administration of the drug.

Compared to normal tissues, most types of cancers are especially active in both the uptake and accumulation of photosensitizers agents, which makes cancers especially vulnerable to PDT.[19] Since photosensitizers can also have a high affinity for vascular endothelial cells.[20]

Acne

PDT is currently in clinical trials as a treatment for severe acne. Initial results have shown for it to be effective as a treatment only for severe acne.[21] The treatment causes severe redness and moderate to severe pain and burning sensation. (see also: Levulan) One phase II trial, while it showed improvement, was not superior to blue/violet light alone.[22]

Ophthalmology

As cited above, verteporfin was widely approved for the treatment of wet AMD beginning in 1999. The drug targets the neovasculature that is caused by the condition.

History

Modern era

In the late nineteenth century. Finsen successfully demonstrated phototherapy by employing heat-filtered light from a carbon-arc lamp (the "Finsen lamp") in the treatment of a tubercular condition of the skin known as lupus vulgaris, for which he won the 1903 Nobel Prize in Physiology or Medicine.[5]

In 1913 another German scientist, Meyer-Betz, described the major stumbling block of photodynamic therapy. After injecting himself with haematoporphyrin (Hp, a photosensitiser), he swiftly experienced a general skin sensitivity upon exposure to sunlight—a recurrent problem with many photosensitisers.[5]

The first evidence that agents, photosensitive synthetic dyes, in combination with a light source and oxygen could have potential therapeutic effect was made at the turn of the 20th century in the laboratory of Hermann von Tappeiner in Munich, Germany. Germany was leading the world in industrial dye synthesis at the time.[5]

While studying the effects of acridine on paramecia cultures, Oscar Raab, a student of von Tappeiner observed a toxic effect. Fortuitously Raab also observed that light was required to kill the paramecia.[23] Subsequent work in von Tappeiner's laboratory showed that oxygen was essential for the 'photodynamic action' – a term coined by von Tappeiner.[24]

Von Tappeiner and colleagues performed the first PDT trial in patients with skin carcinoma using the photosensitizer, eosin. Of 6 patients with a facial basal cell carcinoma, treated with a 1% eosin solution and long-term exposure either to sunlight or arc-lamp light, 4 patients showed total tumour resolution and a relapse-free period of 12 months.[25]

In 1924 Policard revealed the diagnostic capabilities of hematoporphyrin fluorescence when he observed that ultraviolet radiation excited red fluorescence in the sarcomas of laboratory rats.[26] Policard hypothesized that the fluorescence was associated with endogenous hematoporphyrin accumulation.

In 1948 Figge and co-workers[27] showed on laboratory animals that porphyrins exhibit a preferential affinity to rapidly dividing cells, including malignant, embryonic and regenerative cells. They proposed that porphyrins could be used to treat cancer.

Photosensitizer Haematoporphyrin Derivative (HpD), was first characterised in 1960 by Lipson.[28] Lipson sought a diagnostic agent suitable for tumor detection. HpD allowed Lipson to pioneer the use of endoscopes and HpD fluorescence.[29] HpD is a porphyrin species derived from haematoporphyrin, Porphyrins have long been considered as suitable agents for tumour photodiagnosis and tumour PDT because cancerous cells exhibit significantly greater uptake and affinity for porphyrins compared to normal tissues. This had been observed by other researchers prior to Lipson.

Thomas Dougherty and co-workers[30] at Roswell Park Cancer Institute, Buffalo NY, clinically tested PDT in 1978. They treated 113 cutaneous or subcutaneous malignant tumors with HpD and observed total or partial resolution of 111 tumors.[31] Dougherty helped expand clinical trials and formed the International Photodynamic Association, in 1986.[citation needed]

John Toth, product manager for Cooper Medical Devices Corp/Cooper Lasersonics, noticed the "photodynamic chemical effect" of the therapy and wrote the first white paper naming the therapy "Photodynamic Therapy" (PDT) with early clinical argon dye lasers circa 1981. The company set up 10 clinical sites in Japan where the term "radiation" had negative connotations.

HpD, under the brand name Photofrin, was the first PDT agent approved for clinical use in 1993 to treat a form of bladder cancer in Canada. Over the next decade, both PDT and the use of HpD received international attention and greater clinical acceptance and led to the first PDT treatments approved by U.S. Food and Drug Administration Japa and parts of Europe for use against certain cancers of the oesophagus and non-small cell lung cancer.[5]

[32] Photofrin had the disadvantages of prolonged patient photosensitivity and a weak long-wavelength absorption (630 nm). This led to the development of second generation photosensitisers, including Verteporfin (a benzoporphyrin derivative, also known as Visudyne) and more recently, third generation targetable photosensitisers, such as antibody-directed photosensitisers.[5]

In the 1980s, David Dolphin, Julia Levy and colleagues developed a novel photosensitizer, verteporfin.[33][34] Verteporfin, a porphyrin derivative, is activated at 690 nm, a much longer wavelength than Photofrin. It has the property of preferential uptake by neovasculature. It has been widely tested for its use in treating skin cancers and received FDA approval in 2000 for the treatment of wet age related macular degeneration. As such it was the first medical treatment ever approved for this condition, which is a major cause of vision loss.

Russia

Russia was the quickest to advance PDT use clinically and made many advances. They pioneered a photosensitizer called Photogem which, like HpD, was derived from haematoporphyrin in 1990 by Mironov and coworkers. Photogem was approved by the Ministry of Health of Russia and tested clinically from February 1992 to 1996. A pronounced therapeutic effect was observed in 91 percent of the 1500 patients. 62 percent had total tumor resolution. A further 29 percent had >50% tumor shrinkage. In early diagnosis patients 92 percent experienced complete resolution.[35]

Russian scientists collaborated with NASA scientists who were looking at the use of LEDs as more suitable light sources, compared to lasers, for PDT applications.[36] [37] [38]

Asia

Since 1990, the Chinese have been developing clinical expertise with PDT, using domestically produced photosensitizers, derived from Haematoporphyrin.[39] China is notable for its expertise in resolving difficult to reach tumours.[40]

Poland

In the 1990s the team of Polish professor Aleksander Sieroń developed the process and devices for PDT treatment, while improving photosensitizer compounds at the University of Bytom in Poland.

Miscellany

PUVA therapy uses psoralen as photosensitiser and UVA ultraviolet as light source, but this form of therapy is usually classified as a separate form of therapy from photodynamic therapy.[41][42]

To allow treatment of deeper tumours some researchers are using internal chemiluminescence to activate the photosensitiser.[43]

See also

References

  1. Laptev R, Nisnevitch M, Siboni G, Malik Z, Firer MA (July 2006). "Intracellular chemiluminescence activates targeted photodynamic destruction of leukaemic cells". Br. J. Cancer. 95 (2): 189–96. doi:10.1038/sj.bjc.6603241. PMC 2360622Freely accessible. PMID 16819545.

 

Therapeutic intervention: 
Disease(s): 

Cardiovascular Treatments

field_vote: 

Here we will list all kinds of treatments for Cardiovascular Disaeses.

EDTA

field_vote: 

EDTA Chelation
The Real "Miracle" Therapy for Vascular Disease, (from http://www.life-enhancement.com/magazine/article/78-edta-chelation-the-real-miracle-therapy-for-vascular-disease)

The story of EDTA chelation therapy is as much political as it is medical. Consider these facts:

  • EDTA chelation may be one of the most effective, least expensive, and safest treatments for heart disease ever developed, yet it is practiced by perhaps only 2,000 physicians in the United States.
  • EDTA chelation is not typically covered by medical insurance, even though insurance companies would save billions of dollars each year if they did.
  • Although they save far more lives than conventional treatments for heart disease and other chronic degenerative diseases at a fraction of the cost, physicians who practice and promote EDTA chelation for these uses have been harassed, vilified, smeared, and, in some cases, driven from their profession by powerful medical societies and government agencies that practice and promote conventional medical treatments.

What Is EDTA Chelation?
EDTA chelation is a therapy by which repeated administrations of a weak synthetic amino acid (EDTA, ethylenediamine tetra-acetic acid) gradually reduce atherosclerotic plaque and other mineral deposits throughout the cardiovascular system by literally dissolving them away.

EDTA chelation has frequently been compared to a "Roto-Rooter" in the cardiovascular system, because it removes plaque and returns the arterial system to a smooth, healthy, pre-atherosclerotic state. A better metaphor might be "Liquid-Plumr," because, where Roto-Rooter violently scrapes deposits off the interior surfaces of your plumbing with a rapidly rotating blade, Liquid-Plumr simply dissolves them away.

Roto-Rooter is a far better metaphor for conventional medical treatments for heart disease, all of which are closely tied to the concept of the cardiovascular system as plumbing. When a pipe/artery gets clogged, simply ream it out or flatten the deposits (angioplasty). If that doesn't work, just cut away the bad section(s) and replace it (them) with a new piece of pipe (coronary artery bypass graft, or CABG). It's the same basic strategy older cities use for replacing their century-old water mains. And we know how successful that is!

"Because EDTA is so effective at removing unwanted minerals and metals from the blood, it has been the standard 'FDA-approved' treatment for lead, mercury, aluminum and cadmium poisoning for more than 50 years."

CABG, known affectionately in the medical profession as "cabbage," is the most frequently performed surgery in the United States. At up to $50,000 per procedure, that indeed amounts to a lot of "cabbage," not only for cardiac surgeons but also for hospitals. As we shall see, these figures provide a powerful incentive for physicians to reject an effective, but inexpensive and unpatentable treatment like EDTA chelation.

It is commonplace for physicians who regularly prescribe EDTA chelation to encounter heart disease patients who have failed all the standard treatments but who make remarkable - even unbelievable - recoveries once given EDTA. Other patients, on waiting lists for CABG surgery, found they did not need the surgery following a series of EDTA chelation treatments.

EDTA exerts its beneficial effects on the body because this molecule is extremely proficient at chemically bonding with mineral and metal ions. This bonding process, known as chelation, is a natural and essential physiologic process that goes on constantly in the body. EDTA's chelating abilities make it ideal for many tasks:

  • Because EDTA is so effective at removing unwanted minerals and metals from the blood, it has been the standard "FDA-approved" treatment for lead, mercury, aluminum and cadmium poisoning for more than 50 years. EDTA normalizes the distribution of most metallic elements in the body.
  • Because it is so safe and effective, EDTA is also used widely as a stabilizer for packaged food. Minute amounts of EDTA (33-800 PPM) added to food help to preserve flavor and color and to retard spoilage and rancidity. (Read your food labels.)
  • Because EDTA inhibits blood clotting so well, it is routinely added to blood samples that are drawn for testing purposes.*
  • EDTA improves calcium and cholesterol metabolism by eliminating metallic catalysts that can damage cell membranes by producing oxygen free radicals.

Thanks to these and probably other effects of EDTA, it has been reported to have a wide variety of benefits.

*If you followed the O.J. Simpson trial, you probably know that EDTA was featured prominently. The defense contended that EDTA, supposedly found in certain of "The Juice's" blood drops at the murder scene, indicated that that blood had spent some time in a collection tube before being "planted" by the LAPD. If there was EDTA in Simpson's blood, though, it may well have come from the meal he ate on the plane ride from Chicago to LA.

EDTA Chelation vs. Conventional Therapy for Vascular Disease
Researchers first started to notice EDTA in the days during and after World War II when men who worked in battery factories or painted ships with lead-based paint began coming down with lead poisoning from their high exposure in these jobs. EDTA was found to be extremely effective for removing the lead from the men's bodies, but what really made people sit up and take notice was an apparent reduction in symptoms of heart disease in many of these men.

The first systematic study of EDTA in people with atherosclerosis was published in 1956.1 When the researchers gave 20 patients with confirmed heart disease a series of 30 I.V. EDTA treatments, 19 of the patients experienced improvement, as measured by an increase in physical activity. Another study 4 years later in a similar population found that 3 months of EDTA infusions resulted in decreases in the severity and frequency of anginal episodes, reduced use of nitroglycerin (a common anti-angina drug), increased work capacity and improved ECG (electrocardiogram) findings.2

It soon became clear from these and later studies that EDTA treatments result in progressive and widespread improvement and stabilization of cardiovascular function. This is in contrast to standard treatments, such as angioplasty or CABG, which instantaneously restore normal function in the few treated arteries, but leave the rest of the body completely untreated (there's every reason to believe that if arteries are clogged in the heart, they're also clogged in other vital organs, like the kidneys and brain). High-tech treatments for heart disease, such as angioplasty and CABG, long hailed as medical breakthroughs, are in fact, oversold, overpriced, and ineffective, especially when compared with EDTA chelation. The truth of this assertion has been demonstrated on numerous occasions over the last 2 decades:

  • The average mortality for CABG surgery is 4% to 10%.3,4 In fact, CABG has no overall effect on improving survival. According to one study published in the New England Journal of Medicine, "As compared with medical therapy, coronary artery bypass surgery appears neither to prolong life nor to prevent myocardial infarction in patients who have mild angina or who are asymptomatic after infarction in the five-year period after coronary angiography."5 By contrast, mortality rates for EDTA chelation, when carried out according to accepted protocols, approaches 0%.6
  • Grafted coronary arteries are more than 10 times as likely to close up again within 3 years compared with coronary arteries that are not replaced with a graft.7 Improved blood flow following EDTA chelation therapy is permanent as long as regular EDTA therapy (either oral or I.V.) is maintained.
  • Significant cerebral dysfunction, especially in older patients, is commonly seen following CABG.8 Because EDTA chelation restores blood flow to the brain, it often results in improved cognition and memory.9
  • Atherosclerosis is typically a body-wide disease. If your coronary arteries are occluded, it's a safe bet that arteries in your brain, kidneys, lungs, and other vital organs are also occluded. Angioplasty or CABG can clean out only a few arteries supplying the heart. Another surgical procedure, endarterectomy, is commonly used to clear out the carotid arteries that supply the brain. When patients who have undergone carotid endarterectomy are treated with EDTA afterwards, the degree of subsequent restenosis (re-occlusion) drops by 10%.10
  • Despite the danger and costs associated with these procedures, they are often only temporary fixes. Restenosis of treated coronary arteries occurs within 6 months in as many as one in three cases.11 By contrast, EDTA chelation permanently removes blood vessel obstructions throughout the body without dangerous and expensive surgery. How well does EDTA chelation work? Virtually every study that has looked at the efficacy of EDTA chelation in vascular disease has demonstrated significant improvements. Here is a brief sampling of a few of the major results:
  • A 1993 meta-analysis of 19 studies of 22,765 patients receiving EDTA chelation therapy for vascular disease found measurable improvement in 87%.12
  • In a study of 2,870 patients with various degrees of degenerative diseases, especially vascular disease, almost 90% of the patients showed excellent improvement, as measured by walking distance, ECG, and Doppler changes.13
  • A small, blinded, crossover study of patients with peripheral vascular disease found significant improvements in walking distance and ankle/brachial blood flow.14
  • In 30 patients with carotid artery stenosis, there was a 30% improvement in blood flow after EDTA treatment.15
  • Using retinal photographs in patients with macular degeneration, one researcher demonstrated significant improvement following EDTA treatment.16
  • EDTA chelation treatment was evaluated in patients with carotid and coronary disease using technetium 99 isotope techniques. Significant improvement in arterial blood flow and ejection fraction (a measure of heart pumping ability) was reported.17,18
  • When 65 patients on the waiting list for CABG surgery for a mean of 6 months were treated with EDTA chelation therapy, the symptoms in 89% (58) improved so much they were able to cancel their surgery. In the same study, of 27 patients recommended for limb amputation due to poor peripheral circulation, EDTA chelation resulted in saving 24 limbs.19

Negative Results?
Of course there have been a few studies that did not (at first) seem to support the efficacy of EDTA chelation therapy. The most prominent apparently well-controlled studies have been two Danish trials 20,21 and a New Zealand trial,22 all of which reported no apparent benefits. A close analysis of these studies, however, revealed problems with both the controls and the interpretation of the data.

"Because EDTA chelation restores blood flow to the brain, it often results in improved cognition and memory."

As noted by Chappell and Janson,6 the standard EDTA chelation treatment protocol was not followed in these trials. They all included primarily smokers (notoriously poor responders) with severe vascular disease who received only 20 I.V. treatments. With such patients, 30 to 40 treatments are normally required before a significant effect is typically seen. Although the New Zealand trial was supposedly placebo-controlled, the "placebo" used actually had chelating properties of its own. Thus, the fact that the differences from "placebo" were small is meaningless.

When the raw data from the New Zealand study were examined, it was found that 26% of the EDTA-treated patients compared with only 12% of the "placebo" controls achieved an improvement of greater than 100% in walking distance; among nonsmokers or smokers who had quit, 66% of the EDTA-treated group increased their walking distance an average of 86% compared with 45% of the controls, who improved by just 56%. Reduced blood flow, as measured by the ankle/brachial index, was found in 6% of the EDTA-treated patients and 35% of the controls. Although the authors of these studies reached negative conclusions, in fact, their data actually supported the use of EDTA chelation.

How Safe Is EDTA Chelation?
EDTA, is a safe, nontoxic substance. The LD50 (so called when the dose will kill 50% of experimental animals) for EDTA is 2000 mg/kg body weight, which makes it about 3.5 times less toxic than aspirin. Although the FDA refuses to approve it for treating vascular disease, EDTA chelation has been the approved treatment for lead or other heavy metal poisoning for 50 years. When administered according to the treatment protocol developed by the American College for Advancement in Medicine (ACAM), I.V. chelation is more than 300 times safer than CABG surgery. Most side effects of treatment involve minor discomfort (eg, nausea, dizziness, headache) that resolves quickly.

The greatest risks occur when an infusion is given too rapidly or in too large a dose. These risks virtually vanish when EDTA is administered by a properly trained physician who follows the ACAM protocol. To the extent that oral EDTA is a completely noninvasive therapy, it is even safer than I.V. EDTA.

I.V. or Oral EDTA?
Most chelation therapy carried out today involves I.V. administration of EDTA, however, oral EDTA, which has a history at least as long as its I.V. cousin, is an option that is only now starting to be appreciated. Clinical experience suggests that oral chelation provides some, but not all, of the benefits of I.V. therapy. Overall, the difference in benefits is more one of degree and speed than of quality.

I.V. therapy has a direct and powerful effect on the body almost instantaneously. An I.V. session usually lasts about 3 to 4 hours, during which about 1500 mg to 3000 mg of EDTA (plus vitamin C and other nutrients) are administered. The number of treatments necessary (generally about 20-50 sessions) depends on the individual's condition. Candidates for I.V. chelation are people that have been diagnosed with serious atherosclerosis, heavy metal poisoning, or symptoms of vascular occlusion or significant calcification of tissues. Only about 3% to 8% of an oral dose of EDTA is absorbed, compared with 100% of an I.V. dose. Therefore, the time and dosage required to achieve the same benefits with the oral form are quite different. What can be achieved in only a few hours with I.V. EDTA chelation may take several weeks or months with oral EDTA chelation. However, oral EDTA may be appropriate for people whose condition does not demand rapid action. For example, oral chelation can be used to:

  • avoid complications and diseases that result from heavy metals and calcification
  • prevent the formation of blood clots, thus reducing your chance of a heart attack or stroke
  • lower the level of blood cholesterol
  • help thin the blood
  • aid in reducing lipid peroxidation, a major cause of atherosclerosis
  • protect the body against certain carcinogens, pathogens and other toxins that can reduce the quality of health

Oral EDTA is not meant to replace I.V. therapy for those people who have serious vascular disease. It is very useful, though, for people who have completed an I.V. course and want to stay on a maintenance program, for people who "for whatever reason" are unable or unwilling to undergo I.V. chelation, and for those whose I.V. treatments may have been interrupted.

The Politics of EDTA Chelation
Organizations like the American Heart Association and the American Medical Association, which condemn EDTA chelation as ineffective for treating vascular disease, often quote the Danish and New Zealand studies, mentioned earlier, to support their position.20-22 What they fail to mention is that the Danish studies were criticized by the Danish Committee for Investigation into Scientific Dishonesty because of improper randomization and double-blinding, as well as premature breaking of the blinding code, which amounted to a deliberate bias. When the results of the New Zealand study were examined by two independent statisticians, it was concluded that the trial actually supported the efficacy of EDTA.23

"Virtually every study that has looked at the efficacy of EDTA chelation in vascular disease has demonstrated significant improvements."

It is unlikely that any other issue in modern medicine has been more highly politicized than that of EDTA chelation therapy, and it is clear that most of the opposition to EDTA is due to the threat this therapy represents, not to patients' health but to the bank balances of orthodox physicians, pharmaceutical companies, and hospitals. Treating cardiovascular diseases is big business in the United States (and the rest of the Western world), bringing in tens of billions of dollars each year.

As Garry Gordon, MD, DO, the "Father of Chelation Therapy" has pointed out, "Every time a surgeon does a heart bypass, he takes home a luxury sports car." Each CABG procedure costs between $25,000 and $50,000; each angioplasty costs about $15,000; drugs for reducing cholesterol, lowering high blood pressure, and normalizing heart rhythm bring the pharmaceutical industry hundreds of millions of dollars each year. And these are just the most common examples. What happens when you add EDTA chelation therapy to this mix?

A course of I.V. EDTA chelation therapy costs between $2000 and $4000; oral EDTA is even less costly. To the degree that these therapies reduce the need for the more expensive conventional therapies - a large degree, indeed - they threaten to diminish the income of a significant portion of the medical establishment. Consider this one example: As noted earlier, in a study of 65 patients who were treated with I.V. EDTA while they were waiting for CABG surgery, 58 (89%) no longer required the procedure.19 At $50,000 per procedure not done, that means that surgeons and hospitals gave up nearly $3 million just for these few patients. Now remember, that CABG is the most common surgical procedure performed in the US (368,000 in 1989).24

Given these figures, it's not hard to understand why the medical profession is so in love with CABG and related procedures. As one physician noted, "It pays the bills." So enamored are they of these procedures that they perform them even when they are not necessary. In an article published in no less prestigious a publication than the Journal of the American Medical Association, the authors concluded that only 56% of the surgeries performed were for appropriate reasons, 30% for equivocal reasons, and 14% for inappropriate reasons. The percentage of appropriate surgeries varied from 37% in some hospitals to 78% in others.25 When you consider that even when it is "appropriate," CABG surgery is no better than conventional medical treatments for improving survival,5 you have to wonder whether the real "miracle" of heart surgery does not entail bringing people back from death's door, as much as turning a common chronic degenerative disease into a source of outrageous fortune. If you needed one example of why the cost of health care has gone into earth orbit, you need look no further than the conventional treatment of heart disease.

"If you needed one example of why the cost of health care has gone into earth orbit, you need look no further than the conventional treatment of heart disease."

Given these figures, it's also not very hard to understand why the medical profession has reacted so violently against physicians who practice chelation therapy, often attempting, in the words of that great seeker of medical truth (that's a joke folks), Dr. Victor Herbert, "to put them out of business." Because EDTA has long been approved for treating heavy metal poisoning, and because physicians are free to use any "approved" medication for any use they see fit, as long it does not endanger the patient, EDTA chelation therapy is perfectly legal. This has not stopped medical boards in a number of states from bringing charges against physicians who prescribe EDTA chelation for vascular disease, smearing them as "quacks," and attempting to restrict the use of this therapy. Fortunately, most of these attempts have failed.23

You can be certain that if EDTA had a large pharmaceutical company advocating its use, these problems would quickly evaporate. But since the patent for EDTA ran out nearly 30 years ago, there are no huge profits to be made from marketing it. With no pot of gold at the end of the EDTA rainbow, no one is going to put up the hundreds of millions of dollars required to do the randomized, double-blind, placebo-controlled clinical trials required to get the FDA to approve EDTA for vascular disease. And with few large, randomized, double-blind, placebo-controlled clinical trials to refer to, the conventional medical establishment feels justified in condemning EDTA therapy as "unproven." It's a familiar "Catch 22" that faces all natural or unpatentable therapies.

Conclusion
While most American physicians choose to remain blind to the benefits of EDTA, those who prescribe it are free to witness its life-enhancing benefits on a daily basis. One of those physicians is Dr. Garry Gordon, whose own life was saved by EDTA and who has been a leader in chelation therapy since the early 1960s. "I have taken on patients who were inoperable, who had already had every known form of bypass surgery, who had no more veins in their legs to strip out and put into their heart, and who were sent home to die, and I could get those people back to full functioning," says Dr. Gordon.

For an interview with Dr. Garry Gordon, see Exclusive Interview with Garry Gordon, M.D., D.O.: Oral Chelation for Improved Heart Function - Apr. 1997  
POTENTIAL BENEFITS OF EDTA CHELATION
Prevents cholesterol deposits
Reduces blood cholesterol levels
Lowers high blood pressure
Avoids by-pass surgery
Avoids angioplasty
Reserves digitalis toxicity
Removes calcium from atherosclerotic plaques
Dissolves intra-arterial blood clots
Normalizes cardiac arrythmias
Has an anti-aging effect
Reduces excessive heart contractions
Increases intracellular potassium
Reduces heart irritability
Improves heart function
Removes mineral and drug deposits
Dissolves kidney stones
Reduces serum iron levels
Reduces heart valve calcification
Reduces varicose veins
Heals calcified necrotic ulcers
Reduces intermittent claudication
Improves vision in diabetic retinopathy
Decreases macular degeneration
Dissolves small cataracts
Eliminates heavy metal toxicity
Makes arterial walls more flexible
Prevents osteoarthritis
Reduces rheumatoid arthritis symptoms
Lowers diabetics' insulin needs
Reduces Alzheimer-like symptoms
Reverses senility
Reduce stroke/heart attack after-effects
Prevents cancer
Improves memory
Reverses diabetic gangrene
Restores impaired vision
Detoxifies snake and spider venoms

Adapted from Walker M., Gordon G., Douglass W.C. The Chelation Answer

References

1. Clarke NE, Clarke CN, Mosher RE. Treatment of angina pectoris with disodium ethylene diamine tetraacetic acid. Am J Med Sci. 1956;December:654-666.
2. Meltzer LE, Ural E, Kitchell JR. The treatment of coronary artery heart disease with disodium EDTA. In: Seven M, ed. Metal-Binding in Medicine. Philadelphia: JB Lippincott; 1960.
3. Edmunds LH, Stephenson LW, Edie RN, Ratcliffe MB. Open-heart surgery in octogenarians. N Engl J Med. 1988;319:131-136.
4. CASS Principal Investigators and the Associates. Coronary artery surgery study (CASS): a randomized trial of coronary artery bypass surgery: Survival data. Circulation. 1983;68:939-950.
5. CASS Principal Investigators and the Associates. Myocardial infarction and mortality in the Coronary Artery Surgery Study randomized trial. N Engl J Med. 1984;310:750-758.
6. Chappell LT, Janson M. EDTA chelation therapy in the treatment of vascular disease. J Cardiovasc Nurs. 1996;10:78-86.
7. Cashin WL, Sanmarco ME, Nessim SA, Blankenhorn DH. Accelerated progression of atherosclerosis in coronary vessels with minimal lesions that are bypassed. N Engl J Med. 1984;311:824-828.
8. Arom KV, Cohen DE, Strobl FT. Effect of intraoperative intervention on neurological outcome based on electroencephalographic monitoring during cardiopulmonary bypass. Ann Thorac Surg. 1988;48:476-483.
9. Olszewer E, Carter JP. EDTA chelation therapy in chronic degenerative disease. Med Hypotheses. 1988;27:41-49.
10. Holliday HJ. Carotid restenosis: A case for EDTA chelation. J Adv Med. 1996;9.
11. Parisi AF, Folland ED, Hartigan PA. Comparison of angioplasty with medical therapy in the treatment of single-vessel coronary artery disease. N Engl J Med. 1992;326:10-16.
12. Chappell LT, Stahl JP. The correlation between EDTA chelation therapy and improvement in cardiovascular function: a meta-analysis. J Adv Med. 1993;6:139-160.
13. Olszewer E, Carter JP. EDTA chelation therapy in chronic degenerative disease. Med Hypotheses. 1988;27:41-49.
14. Olszewer E, Sabbag FC, Carter JP. A pilot double-blind study of sodium-magnesium EDTA in peripheral vascular disease. J Natl Med Assoc. 1990;82:173-174.
15. Rudolph CJ, McDonagh EW, Barber RK. A non-surgical approach to obstructive carotid stenosis using EDTA chelation. J Adv Med. 1991;4:157-166.
16. Rudolph CJ, Samuels RT, McDonagh EW. Visual field evidence of macular degeneration reversal using a combination of EDTA chelation and multiple vitamin and trace mineral therapy. J Adv Med. 1994;7:203-212.
17. Casdorph HR. EDTA chelation therapy, II: efficacy in brain disorders. J Holist Med. 1981;3:101-117.
18. Casdorph HR. EDTA chelation therapy: efficacy in arteriosclerotic heart disease. J Holist Med. 1981;3:53-59.
19. Hancke C, Flytie K. Benefits of EDTA chelation therapy on arteriosclerosis. J Adv Med. 1993;6:161-172.
20. Sloth-Nielsen J, Guldager B, Mouritzen C, et al. Arteriographic findings in EDTA chelation therapy on peripheral arteriosclerosis. Am J Surg. 1991;162:122-125.
21. Guldager B, Jelnes R, Jorgensen SJ, et al. EDTA treatment of intermittent claudication - a double-blind, placebo-controlled study. J Intern Med. 1992;231:261-267.
22. van Rij AM, Solomon C, Packer SGK, Hopkins WG. Chelation therapy for intermittent claudication: a double-blind, randomized, controlled trial. Circulation. 1994;90:1194-1199.
23. Schachter MB. Overview, historical background and current status of EDTA chelation therapy for atherosclerosis. J Adv Med. 1996;9:159-177.
24. Gundy P. Cardiovascular diseases remain nation's leading cause of death. JAMA. 1992;267:335-336.
25. Winslow CM, Kosecoff JB, Chassin M, Kanouse DE, Brook RH. The appropriateness of performing coronary artery bypass surgery. JAMA. 1988;260:505-509.

Therapeutic Substance(s): 
Therapeutic intervention: 

Hibiscus as medical herb Hibiscus sabdariffa L.

field_vote: 

A double-blind, placebo-controlled clinical trial was conducted in 65 men and women, age 30 –70 y, with systolic BP Daily consumption of 3 c hibiscus tea, an amount readily incorporated into the diet, lowers BP in pre- and mildly hypertensive adults and may prove an effective component of the dietary changes recommended for people at risk of developing hypertension.

Therapeutic intervention: 

Lyme Treatment

field_vote: 

Lymes Disease, or more adequately Chronic Systemic Multiinfection Disease Syndrome is a disease caused by a combination of bacterias, parasites and viruses with the common denominator that they all have an ability to depress immune function, which in turn makes the body susceptible to even more infections. It is like a burglar entering your house, turning of the burglar alarm, and then inviting all his friends to have a party....

It is often, but notalways related to tick bites...
Recent reserach has demonstrated that Babesiosis ca be transmitted by blood transfusions, and that this is very hard to prevent as detection methods are unprecise.

The most common infections are differents types of Borrelia, Babesia, Bartonella, Ehrlichia, Chlamydia Pneumoniae, Mycoplasma, Cocksackie Virus, Epsein Barr Virus, Herpes Simplex type 6 virus, Rickettsia etc

Lyme disease is transmitted by the bite of a tick, and the disease is prevalent across the United States and throughout the world. Ticks know no borders and respect no boundaries. A patient's county of residence does not accurately reflect his or her Lyme disease risk because people travel, pets travel, and ticks travel. This creates a dynamic situation with many opportunities for exposure to Lyme disease for each individual. - See more at: http://www.ilads.org/lyme/about-lyme.php#sthash.ydRjEJtT.dpuf

Basic Information about Lyme Disease

By The International Lyme and Associated Diseases Society

  1. 1

    Lyme disease is transmitted by the bite of a tick, and the disease is prevalent across the United States and throughout the world. Ticks know no borders and respect no boundaries. A patient's county of residence does not accurately reflect his or her Lyme disease risk because people travel, pets travel, and ticks travel. This creates a dynamic situation with many opportunities for exposure to Lyme disease for each individual.

  2. 2

    Lyme disease is a clinical diagnosis. The disease is caused by a spiral-shaped bacteria (spirochete) called Borrelia Burgdorferi. The Lyme spirochete can cause infection of multiple organs and produce a wide range of symptoms. Case reports in the medical literature document the protean manifestations of Lyme disease, and familiarity with its varied presentations is key to recognizing disseminated disease.

  3. 3

    Fewer than 50% of patients with Lyme disease recall a tick bite. In some studies this number is as low as 15% in culture-proven infection with the Lyme spirochete.

  4. 4

    Fewer than 50% of patients with Lyme disease recall any rash. Although the erythema migrans (EM) or “bull’s-eye” rash is considered classic, it is not the most common dermatologic manifestation of early-localized Lyme infection. Atypical forms of this rash are seen far more commonly. It is important to know that the EM rash is pathognomonic of Lyme disease and requires no further verification prior to starting an appropriate course of antibiotic therapy.

  5. 5

    The Centers For Disease Control And Prevention (CDC) surveillance criteria for Lyme disease were devised to track a narrow band of cases for epidemiologic purposes. As stated on the CDC website, the surveillance criteria were never intended to be used as diagnostic criteria, nor were they meant to define the entire scope of Lyme disease.

  6. 6

    The elisa screening test is unreliable. The test misses 35% of culture proven Lyme disease (only 65% sensitivity) and is unacceptable as the first step of a two-step screening protocol. By definition, a screening test should have at least 95% sensitivity.

  7. 7

    Of patients with acute culture-proven Lyme disease, 20–30% remain seronegative on serial western blot sampling. Antibody titers also appear to decline over time; thus while the western blot may remain positive for months, it may not always be sensitive enough to detect chronic infection with the Lyme spirochete. For “epidemiological purposes” the CDC eliminated from the western blot analysis the reading of bands 31 and 34. These bands are so specific to Borrelia Burgdorferi that they were chosen for vaccine development. Since a vaccine for Lyme disease is currently unavailable, however, a positive 31 or 34 band is highly indicative of Borrelia Burgdorferi exposure. Yet these bands are not reported in commercial Lyme tests.

  8. 8

    When used as part of a diagnostic evaluation for Lyme disease, the western blot should be performed by a laboratory that reads and reports all of the bands related to Borrelia Burgdorferi. Laboratories that use FDA approved kits (for instance, the mardx marblot®) are restricted from reporting all of the bands, as they must abide by the rules of the manufacturer. These rules are set up in accordance with the CDC's surveillance criteria and increase the risk of false-negative results. The commercial kits may be useful for surveillance purposes, but they offer too little information to be useful in patient management.

  9. 9

    There are 5 subspecies of Borrelia Burgdorferi, over 100 strains in the USA, and 300 strains worldwide. This diversity is thought to contribute to the antigenic variability of the spirochete and its ability to evade the immune system and antibiotic therapy, leading to chronic infection.

  10. 10

    Testing for Babesia, Anaplasma, Ehrlichia and Bartonella (other tick-transmitted organisms) should be performed. The presence of co-infection with these organisms points to probable infection with the Lyme spirochete as well. If these coinfections are left untreated, their continued presence increases morbidity and prevents successful treatment of Lyme disease.

  11. 11

    A preponderance of evidence indicates that active ongoing spirochetal infection with or without other tick-borne coinfections is the cause of the persistent symptoms in chronic Lyme disease.

  12. 12

    There has never been a study demonstrating that 30 days of antibiotic treatment cures chronic Lyme disease. However there is a plethora of documentation in the us and european medical literature demonstrating by histology and culture techniques that short courses of antibiotic treatment fail to eradicate the Lyme spirochete. Short treatment courses have resulted in upwards of a 40% relapse rate, especially if treatment is delayed.

  13. 13

    Most cases of chronic Lyme disease require an extended course of antibiotic therapy to achieve symptomatic relief. The return of symptoms and evidence of the continued presence of Borrelia Burgdorferi indicates the need for further treatment. The very real consequences of untreated chronic persistent Lyme infection far outweigh the potential consequences of long-term antibiotic therapy.

  14. 14

    Many patients with chronic Lyme disease require prolonged treatment until the patient is symptom-free. Relapses occur and retreatment may be required. There are no tests currently available to provethat the organism is eradicated or that the patient with chronic Lyme disease is cured.

  15. 15

    Like Syphilis in the 19th century, Lyme disease has been called the great imitator and should be considered in the differential diagnosis of rheumatologic and neurologic conditions, as well as Chronic Fatigue Syndrome, Fibromyalgia, Somatization Disorder and any difficult-to-diagnose multi-system illness.

Disclaimer: The foregoing information is for educational purposes only. It is not intended to replace or supersede patient care by a healthcare provider. If an individual suspects the presence of a tick-borne illness, that individual should consult a healthcare provider who is familiar with the diagnosis and treatment of tick-borne diseases.

- See more at: http://www.ilads.org/lyme/about-lyme.php#sthash.ydRjEJtT.dpuf

Basic Information about Lyme Disease

By The International Lyme and Associated Diseases Society

  1. 1

    Lyme disease is transmitted by the bite of a tick, and the disease is prevalent across the United States and throughout the world. Ticks know no borders and respect no boundaries. A patient's county of residence does not accurately reflect his or her Lyme disease risk because people travel, pets travel, and ticks travel. This creates a dynamic situation with many opportunities for exposure to Lyme disease for each individual.

  2. 2

    Lyme disease is a clinical diagnosis. The disease is caused by a spiral-shaped bacteria (spirochete) called Borrelia Burgdorferi. The Lyme spirochete can cause infection of multiple organs and produce a wide range of symptoms. Case reports in the medical literature document the protean manifestations of Lyme disease, and familiarity with its varied presentations is key to recognizing disseminated disease.

  3. 3

    Fewer than 50% of patients with Lyme disease recall a tick bite. In some studies this number is as low as 15% in culture-proven infection with the Lyme spirochete.

  4. 4

    Fewer than 50% of patients with Lyme disease recall any rash. Although the erythema migrans (EM) or “bull’s-eye” rash is considered classic, it is not the most common dermatologic manifestation of early-localized Lyme infection. Atypical forms of this rash are seen far more commonly. It is important to know that the EM rash is pathognomonic of Lyme disease and requires no further verification prior to starting an appropriate course of antibiotic therapy.

  5. 5

    The Centers For Disease Control And Prevention (CDC) surveillance criteria for Lyme disease were devised to track a narrow band of cases for epidemiologic purposes. As stated on the CDC website, the surveillance criteria were never intended to be used as diagnostic criteria, nor were they meant to define the entire scope of Lyme disease.

  6. 6

    The elisa screening test is unreliable. The test misses 35% of culture proven Lyme disease (only 65% sensitivity) and is unacceptable as the first step of a two-step screening protocol. By definition, a screening test should have at least 95% sensitivity.

  7. 7

    Of patients with acute culture-proven Lyme disease, 20–30% remain seronegative on serial western blot sampling. Antibody titers also appear to decline over time; thus while the western blot may remain positive for months, it may not always be sensitive enough to detect chronic infection with the Lyme spirochete. For “epidemiological purposes” the CDC eliminated from the western blot analysis the reading of bands 31 and 34. These bands are so specific to Borrelia Burgdorferi that they were chosen for vaccine development. Since a vaccine for Lyme disease is currently unavailable, however, a positive 31 or 34 band is highly indicative of Borrelia Burgdorferi exposure. Yet these bands are not reported in commercial Lyme tests.

  8. 8

    When used as part of a diagnostic evaluation for Lyme disease, the western blot should be performed by a laboratory that reads and reports all of the bands related to Borrelia Burgdorferi. Laboratories that use FDA approved kits (for instance, the mardx marblot®) are restricted from reporting all of the bands, as they must abide by the rules of the manufacturer. These rules are set up in accordance with the CDC's surveillance criteria and increase the risk of false-negative results. The commercial kits may be useful for surveillance purposes, but they offer too little information to be useful in patient management.

  9. 9

    There are 5 subspecies of Borrelia Burgdorferi, over 100 strains in the USA, and 300 strains worldwide. This diversity is thought to contribute to the antigenic variability of the spirochete and its ability to evade the immune system and antibiotic therapy, leading to chronic infection.

  10. 10

    Testing for Babesia, Anaplasma, Ehrlichia and Bartonella (other tick-transmitted organisms) should be performed. The presence of co-infection with these organisms points to probable infection with the Lyme spirochete as well. If these coinfections are left untreated, their continued presence increases morbidity and prevents successful treatment of Lyme disease.

  11. 11

    A preponderance of evidence indicates that active ongoing spirochetal infection with or without other tick-borne coinfections is the cause of the persistent symptoms in chronic Lyme disease.

  12. 12

    There has never been a study demonstrating that 30 days of antibiotic treatment cures chronic Lyme disease. However there is a plethora of documentation in the us and european medical literature demonstrating by histology and culture techniques that short courses of antibiotic treatment fail to eradicate the Lyme spirochete. Short treatment courses have resulted in upwards of a 40% relapse rate, especially if treatment is delayed.

  13. 13

    Most cases of chronic Lyme disease require an extended course of antibiotic therapy to achieve symptomatic relief. The return of symptoms and evidence of the continued presence of Borrelia Burgdorferi indicates the need for further treatment. The very real consequences of untreated chronic persistent Lyme infection far outweigh the potential consequences of long-term antibiotic therapy.

  14. 14

    Many patients with chronic Lyme disease require prolonged treatment until the patient is symptom-free. Relapses occur and retreatment may be required. There are no tests currently available to provethat the organism is eradicated or that the patient with chronic Lyme disease is cured.

  15. 15

    Like Syphilis in the 19th century, Lyme disease has been called the great imitator and should be considered in the differential diagnosis of rheumatologic and neurologic conditions, as well as Chronic Fatigue Syndrome, Fibromyalgia, Somatization Disorder and any difficult-to-diagnose multi-system illness.

Disclaimer: The foregoing information is for educational purposes only. It is not intended to replace or supersede patient care by a healthcare provider. If an individual suspects the presence of a tick-borne illness, that individual should consult a healthcare provider who is familiar with the diagnosis and treatment of tick-borne diseases.

- See more at: http://www.ilads.org/lyme/about-lyme.php#sthash.ydRjEJtT.dpuf

Basic Information about Lyme Disease

By The International Lyme and Associated Diseases Society

  1. 1

    Lyme disease is transmitted by the bite of a tick, and the disease is prevalent across the United States and throughout the world. Ticks know no borders and respect no boundaries. A patient's county of residence does not accurately reflect his or her Lyme disease risk because people travel, pets travel, and ticks travel. This creates a dynamic situation with many opportunities for exposure to Lyme disease for each individual.

  2. 2

    Lyme disease is a clinical diagnosis. The disease is caused by a spiral-shaped bacteria (spirochete) called Borrelia Burgdorferi. The Lyme spirochete can cause infection of multiple organs and produce a wide range of symptoms. Case reports in the medical literature document the protean manifestations of Lyme disease, and familiarity with its varied presentations is key to recognizing disseminated disease.

  3. 3

    Fewer than 50% of patients with Lyme disease recall a tick bite. In some studies this number is as low as 15% in culture-proven infection with the Lyme spirochete.

  4. 4

    Fewer than 50% of patients with Lyme disease recall any rash. Although the erythema migrans (EM) or “bull’s-eye” rash is considered classic, it is not the most common dermatologic manifestation of early-localized Lyme infection. Atypical forms of this rash are seen far more commonly. It is important to know that the EM rash is pathognomonic of Lyme disease and requires no further verification prior to starting an appropriate course of antibiotic therapy.

  5. 5

    The Centers For Disease Control And Prevention (CDC) surveillance criteria for Lyme disease were devised to track a narrow band of cases for epidemiologic purposes. As stated on the CDC website, the surveillance criteria were never intended to be used as diagnostic criteria, nor were they meant to define the entire scope of Lyme disease.

  6. 6

    The elisa screening test is unreliable. The test misses 35% of culture proven Lyme disease (only 65% sensitivity) and is unacceptable as the first step of a two-step screening protocol. By definition, a screening test should have at least 95% sensitivity.

  7. 7

    Of patients with acute culture-proven Lyme disease, 20–30% remain seronegative on serial western blot sampling. Antibody titers also appear to decline over time; thus while the western blot may remain positive for months, it may not always be sensitive enough to detect chronic infection with the Lyme spirochete. For “epidemiological purposes” the CDC eliminated from the western blot analysis the reading of bands 31 and 34. These bands are so specific to Borrelia Burgdorferi that they were chosen for vaccine development. Since a vaccine for Lyme disease is currently unavailable, however, a positive 31 or 34 band is highly indicative of Borrelia Burgdorferi exposure. Yet these bands are not reported in commercial Lyme tests.

  8. 8

    When used as part of a diagnostic evaluation for Lyme disease, the western blot should be performed by a laboratory that reads and reports all of the bands related to Borrelia Burgdorferi. Laboratories that use FDA approved kits (for instance, the mardx marblot®) are restricted from reporting all of the bands, as they must abide by the rules of the manufacturer. These rules are set up in accordance with the CDC's surveillance criteria and increase the risk of false-negative results. The commercial kits may be useful for surveillance purposes, but they offer too little information to be useful in patient management.

  9. 9

    There are 5 subspecies of Borrelia Burgdorferi, over 100 strains in the USA, and 300 strains worldwide. This diversity is thought to contribute to the antigenic variability of the spirochete and its ability to evade the immune system and antibiotic therapy, leading to chronic infection.

  10. 10

    Testing for Babesia, Anaplasma, Ehrlichia and Bartonella (other tick-transmitted organisms) should be performed. The presence of co-infection with these organisms points to probable infection with the Lyme spirochete as well. If these coinfections are left untreated, their continued presence increases morbidity and prevents successful treatment of Lyme disease.

  11. 11

    A preponderance of evidence indicates that active ongoing spirochetal infection with or without other tick-borne coinfections is the cause of the persistent symptoms in chronic Lyme disease.

  12. 12

    There has never been a study demonstrating that 30 days of antibiotic treatment cures chronic Lyme disease. However there is a plethora of documentation in the us and european medical literature demonstrating by histology and culture techniques that short courses of antibiotic treatment fail to eradicate the Lyme spirochete. Short treatment courses have resulted in upwards of a 40% relapse rate, especially if treatment is delayed.

  13. 13

    Most cases of chronic Lyme disease require an extended course of antibiotic therapy to achieve symptomatic relief. The return of symptoms and evidence of the continued presence of Borrelia Burgdorferi indicates the need for further treatment. The very real consequences of untreated chronic persistent Lyme infection far outweigh the potential consequences of long-term antibiotic therapy.

  14. 14

    Many patients with chronic Lyme disease require prolonged treatment until the patient is symptom-free. Relapses occur and retreatment may be required. There are no tests currently available to provethat the organism is eradicated or that the patient with chronic Lyme disease is cured.

  15. 15

    Like Syphilis in the 19th century, Lyme disease has been called the great imitator and should be considered in the differential diagnosis of rheumatologic and neurologic conditions, as well as Chronic Fatigue Syndrome, Fibromyalgia, Somatization Disorder and any difficult-to-diagnose multi-system illness.

Disclaimer: The foregoing information is for educational purposes only. It is not intended to replace or supersede patient care by a healthcare provider. If an individual suspects the presence of a tick-borne illness, that individual should consult a healthcare provider who is familiar with the diagnosis and treatment of tick-borne diseases.

- See more at: http://www.ilads.org/lyme/about-lyme.php#sthash.ydRjEJtT.dpuf

Basic Information about Lyme Disease

By The International Lyme and Associated Diseases Society

  1. 1

    Lyme disease is transmitted by the bite of a tick, and the disease is prevalent across the United States and throughout the world. Ticks know no borders and respect no boundaries. A patient's county of residence does not accurately reflect his or her Lyme disease risk because people travel, pets travel, and ticks travel. This creates a dynamic situation with many opportunities for exposure to Lyme disease for each individual.

  2. 2

    Lyme disease is a clinical diagnosis. The disease is caused by a spiral-shaped bacteria (spirochete) called Borrelia Burgdorferi. The Lyme spirochete can cause infection of multiple organs and produce a wide range of symptoms. Case reports in the medical literature document the protean manifestations of Lyme disease, and familiarity with its varied presentations is key to recognizing disseminated disease.

  3. 3

    Fewer than 50% of patients with Lyme disease recall a tick bite. In some studies this number is as low as 15% in culture-proven infection with the Lyme spirochete.

  4. 4

    Fewer than 50% of patients with Lyme disease recall any rash. Although the erythema migrans (EM) or “bull’s-eye” rash is considered classic, it is not the most common dermatologic manifestation of early-localized Lyme infection. Atypical forms of this rash are seen far more commonly. It is important to know that the EM rash is pathognomonic of Lyme disease and requires no further verification prior to starting an appropriate course of antibiotic therapy.

  5. 5

    The Centers For Disease Control And Prevention (CDC) surveillance criteria for Lyme disease were devised to track a narrow band of cases for epidemiologic purposes. As stated on the CDC website, the surveillance criteria were never intended to be used as diagnostic criteria, nor were they meant to define the entire scope of Lyme disease.

  6. 6

    The elisa screening test is unreliable. The test misses 35% of culture proven Lyme disease (only 65% sensitivity) and is unacceptable as the first step of a two-step screening protocol. By definition, a screening test should have at least 95% sensitivity.

  7. 7

    Of patients with acute culture-proven Lyme disease, 20–30% remain seronegative on serial western blot sampling. Antibody titers also appear to decline over time; thus while the western blot may remain positive for months, it may not always be sensitive enough to detect chronic infection with the Lyme spirochete. For “epidemiological purposes” the CDC eliminated from the western blot analysis the reading of bands 31 and 34. These bands are so specific to Borrelia Burgdorferi that they were chosen for vaccine development. Since a vaccine for Lyme disease is currently unavailable, however, a positive 31 or 34 band is highly indicative of Borrelia Burgdorferi exposure. Yet these bands are not reported in commercial Lyme tests.

  8. 8

    When used as part of a diagnostic evaluation for Lyme disease, the western blot should be performed by a laboratory that reads and reports all of the bands related to Borrelia Burgdorferi. Laboratories that use FDA approved kits (for instance, the mardx marblot®) are restricted from reporting all of the bands, as they must abide by the rules of the manufacturer. These rules are set up in accordance with the CDC's surveillance criteria and increase the risk of false-negative results. The commercial kits may be useful for surveillance purposes, but they offer too little information to be useful in patient management.

  9. 9

    There are 5 subspecies of Borrelia Burgdorferi, over 100 strains in the USA, and 300 strains worldwide. This diversity is thought to contribute to the antigenic variability of the spirochete and its ability to evade the immune system and antibiotic therapy, leading to chronic infection.

  10. 10

    Testing for Babesia, Anaplasma, Ehrlichia and Bartonella (other tick-transmitted organisms) should be performed. The presence of co-infection with these organisms points to probable infection with the Lyme spirochete as well. If these coinfections are left untreated, their continued presence increases morbidity and prevents successful treatment of Lyme disease.

  11. 11

    A preponderance of evidence indicates that active ongoing spirochetal infection with or without other tick-borne coinfections is the cause of the persistent symptoms in chronic Lyme disease.

  12. 12

    There has never been a study demonstrating that 30 days of antibiotic treatment cures chronic Lyme disease. However there is a plethora of documentation in the us and european medical literature demonstrating by histology and culture techniques that short courses of antibiotic treatment fail to eradicate the Lyme spirochete. Short treatment courses have resulted in upwards of a 40% relapse rate, especially if treatment is delayed.

  13. 13

    Most cases of chronic Lyme disease require an extended course of antibiotic therapy to achieve symptomatic relief. The return of symptoms and evidence of the continued presence of Borrelia Burgdorferi indicates the need for further treatment. The very real consequences of untreated chronic persistent Lyme infection far outweigh the potential consequences of long-term antibiotic therapy.

  14. 14

    Many patients with chronic Lyme disease require prolonged treatment until the patient is symptom-free. Relapses occur and retreatment may be required. There are no tests currently available to provethat the organism is eradicated or that the patient with chronic Lyme disease is cured.

  15. 15

    Like Syphilis in the 19th century, Lyme disease has been called the great imitator and should be considered in the differential diagnosis of rheumatologic and neurologic conditions, as well as Chronic Fatigue Syndrome, Fibromyalgia, Somatization Disorder and any difficult-to-diagnose multi-system illness.

Disclaimer: The foregoing information is for educational purposes only. It is not intended to replace or supersede patient care by a healthcare provider. If an individual suspects the presence of a tick-borne illness, that individual should consult a healthcare provider who is familiar with the diagnosis and treatment of tick-borne diseases.

- See more at: http://www.ilads.org/lyme/about-lyme.php#sthash.ydRjEJtT.dpuf

Basic Information about Lyme Disease

By The International Lyme and Associated Diseases Society

  1. 1

    Lyme disease is transmitted by the bite of a tick, and the disease is prevalent across the United States and throughout the world. Ticks know no borders and respect no boundaries. A patient's county of residence does not accurately reflect his or her Lyme disease risk because people travel, pets travel, and ticks travel. This creates a dynamic situation with many opportunities for exposure to Lyme disease for each individual.

  2. 2

    Lyme disease is a clinical diagnosis. The disease is caused by a spiral-shaped bacteria (spirochete) called Borrelia Burgdorferi. The Lyme spirochete can cause infection of multiple organs and produce a wide range of symptoms. Case reports in the medical literature document the protean manifestations of Lyme disease, and familiarity with its varied presentations is key to recognizing disseminated disease.

  3. 3

    Fewer than 50% of patients with Lyme disease recall a tick bite. In some studies this number is as low as 15% in culture-proven infection with the Lyme spirochete.

  4. 4

    Fewer than 50% of patients with Lyme disease recall any rash. Although the erythema migrans (EM) or “bull’s-eye” rash is considered classic, it is not the most common dermatologic manifestation of early-localized Lyme infection. Atypical forms of this rash are seen far more commonly. It is important to know that the EM rash is pathognomonic of Lyme disease and requires no further verification prior to starting an appropriate course of antibiotic therapy.

  5. 5

    The Centers For Disease Control And Prevention (CDC) surveillance criteria for Lyme disease were devised to track a narrow band of cases for epidemiologic purposes. As stated on the CDC website, the surveillance criteria were never intended to be used as diagnostic criteria, nor were they meant to define the entire scope of Lyme disease.

  6. 6

    The elisa screening test is unreliable. The test misses 35% of culture proven Lyme disease (only 65% sensitivity) and is unacceptable as the first step of a two-step screening protocol. By definition, a screening test should have at least 95% sensitivity.

  7. 7

    Of patients with acute culture-proven Lyme disease, 20–30% remain seronegative on serial western blot sampling. Antibody titers also appear to decline over time; thus while the western blot may remain positive for months, it may not always be sensitive enough to detect chronic infection with the Lyme spirochete. For “epidemiological purposes” the CDC eliminated from the western blot analysis the reading of bands 31 and 34. These bands are so specific to Borrelia Burgdorferi that they were chosen for vaccine development. Since a vaccine for Lyme disease is currently unavailable, however, a positive 31 or 34 band is highly indicative of Borrelia Burgdorferi exposure. Yet these bands are not reported in commercial Lyme tests.

  8. 8

    When used as part of a diagnostic evaluation for Lyme disease, the western blot should be performed by a laboratory that reads and reports all of the bands related to Borrelia Burgdorferi. Laboratories that use FDA approved kits (for instance, the mardx marblot®) are restricted from reporting all of the bands, as they must abide by the rules of the manufacturer. These rules are set up in accordance with the CDC's surveillance criteria and increase the risk of false-negative results. The commercial kits may be useful for surveillance purposes, but they offer too little information to be useful in patient management.

  9. 9

    There are 5 subspecies of Borrelia Burgdorferi, over 100 strains in the USA, and 300 strains worldwide. This diversity is thought to contribute to the antigenic variability of the spirochete and its ability to evade the immune system and antibiotic therapy, leading to chronic infection.

  10. 10

    Testing for Babesia, Anaplasma, Ehrlichia and Bartonella (other tick-transmitted organisms) should be performed. The presence of co-infection with these organisms points to probable infection with the Lyme spirochete as well. If these coinfections are left untreated, their continued presence increases morbidity and prevents successful treatment of Lyme disease.

  11. 11

    A preponderance of evidence indicates that active ongoing spirochetal infection with or without other tick-borne coinfections is the cause of the persistent symptoms in chronic Lyme disease.

  12. 12

    There has never been a study demonstrating that 30 days of antibiotic treatment cures chronic Lyme disease. However there is a plethora of documentation in the us and european medical literature demonstrating by histology and culture techniques that short courses of antibiotic treatment fail to eradicate the Lyme spirochete. Short treatment courses have resulted in upwards of a 40% relapse rate, especially if treatment is delayed.

  13. 13

    Most cases of chronic Lyme disease require an extended course of antibiotic therapy to achieve symptomatic relief. The return of symptoms and evidence of the continued presence of Borrelia Burgdorferi indicates the need for further treatment. The very real consequences of untreated chronic persistent Lyme infection far outweigh the potential consequences of long-term antibiotic therapy.

  14. 14

    Many patients with chronic Lyme disease require prolonged treatment until the patient is symptom-free. Relapses occur and retreatment may be required. There are no tests currently available to provethat the organism is eradicated or that the patient with chronic Lyme disease is cured.

  15. 15

    Like Syphilis in the 19th century, Lyme disease has been called the great imitator and should be considered in the differential diagnosis of rheumatologic and neurologic conditions, as well as Chronic Fatigue Syndrome, Fibromyalgia, Somatization Disorder and any difficult-to-diagnose multi-system illness.

Disclaimer: The foregoing information is for educational purposes only. It is not intended to replace or supersede patient care by a healthcare provider. If an individual suspects the presence of a tick-borne illness, that individual should consult a healthcare provider who is familiar with the diagnosis and treatment of tick-borne diseases.

- See more at: http://www.ilads.org/lyme/about-lyme.php#sthash.ydRjEJtT.dpuf

Basic Information about Lyme Disease

By The International Lyme and Associated Diseases Society

  1. 1

    Lyme disease is transmitted by the bite of a tick, and the disease is prevalent across the United States and throughout the world. Ticks know no borders and respect no boundaries. A patient's county of residence does not accurately reflect his or her Lyme disease risk because people travel, pets travel, and ticks travel. This creates a dynamic situation with many opportunities for exposure to Lyme disease for each individual.

  2. 2

    Lyme disease is a clinical diagnosis. The disease is caused by a spiral-shaped bacteria (spirochete) called Borrelia Burgdorferi. The Lyme spirochete can cause infection of multiple organs and produce a wide range of symptoms. Case reports in the medical literature document the protean manifestations of Lyme disease, and familiarity with its varied presentations is key to recognizing disseminated disease.

  3. 3

    Fewer than 50% of patients with Lyme disease recall a tick bite. In some studies this number is as low as 15% in culture-proven infection with the Lyme spirochete.

  4. 4

    Fewer than 50% of patients with Lyme disease recall any rash. Although the erythema migrans (EM) or “bull’s-eye” rash is considered classic, it is not the most common dermatologic manifestation of early-localized Lyme infection. Atypical forms of this rash are seen far more commonly. It is important to know that the EM rash is pathognomonic of Lyme disease and requires no further verification prior to starting an appropriate course of antibiotic therapy.

  5. 5

    The Centers For Disease Control And Prevention (CDC) surveillance criteria for Lyme disease were devised to track a narrow band of cases for epidemiologic purposes. As stated on the CDC website, the surveillance criteria were never intended to be used as diagnostic criteria, nor were they meant to define the entire scope of Lyme disease.

  6. 6

    The elisa screening test is unreliable. The test misses 35% of culture proven Lyme disease (only 65% sensitivity) and is unacceptable as the first step of a two-step screening protocol. By definition, a screening test should have at least 95% sensitivity.

  7. 7

    Of patients with acute culture-proven Lyme disease, 20–30% remain seronegative on serial western blot sampling. Antibody titers also appear to decline over time; thus while the western blot may remain positive for months, it may not always be sensitive enough to detect chronic infection with the Lyme spirochete. For “epidemiological purposes” the CDC eliminated from the western blot analysis the reading of bands 31 and 34. These bands are so specific to Borrelia Burgdorferi that they were chosen for vaccine development. Since a vaccine for Lyme disease is currently unavailable, however, a positive 31 or 34 band is highly indicative of Borrelia Burgdorferi exposure. Yet these bands are not reported in commercial Lyme tests.

  8. 8

    When used as part of a diagnostic evaluation for Lyme disease, the western blot should be performed by a laboratory that reads and reports all of the bands related to Borrelia Burgdorferi. Laboratories that use FDA approved kits (for instance, the mardx marblot®) are restricted from reporting all of the bands, as they must abide by the rules of the manufacturer. These rules are set up in accordance with the CDC's surveillance criteria and increase the risk of false-negative results. The commercial kits may be useful for surveillance purposes, but they offer too little information to be useful in patient management.

  9. 9

    There are 5 subspecies of Borrelia Burgdorferi, over 100 strains in the USA, and 300 strains worldwide. This diversity is thought to contribute to the antigenic variability of the spirochete and its ability to evade the immune system and antibiotic therapy, leading to chronic infection.

  10. 10

    Testing for Babesia, Anaplasma, Ehrlichia and Bartonella (other tick-transmitted organisms) should be performed. The presence of co-infection with these organisms points to probable infection with the Lyme spirochete as well. If these coinfections are left untreated, their continued presence increases morbidity and prevents successful treatment of Lyme disease.

  11. 11

    A preponderance of evidence indicates that active ongoing spirochetal infection with or without other tick-borne coinfections is the cause of the persistent symptoms in chronic Lyme disease.

  12. 12

    There has never been a study demonstrating that 30 days of antibiotic treatment cures chronic Lyme disease. However there is a plethora of documentation in the us and european medical literature demonstrating by histology and culture techniques that short courses of antibiotic treatment fail to eradicate the Lyme spirochete. Short treatment courses have resulted in upwards of a 40% relapse rate, especially if treatment is delayed.

  13. 13

    Most cases of chronic Lyme disease require an extended course of antibiotic therapy to achieve symptomatic relief. The return of symptoms and evidence of the continued presence of Borrelia Burgdorferi indicates the need for further treatment. The very real consequences of