Curing cancer? The dichloroacetate story January 31, 2007
Posted by Bertalan Meskó in Cancer, Invention, Medicine, Mystery, Policy and Law, science.trackback
Maybe it seems to be a simple solution for curing cancer, but The E-cclesiastic Manifesto blog writes about a drug called dichloroacetate:
A team led by Dr. Evangelos Michelakis at the University of Alberta in Canada have figured out a new use for a safe, cheap chemical already used in medicine for a host of metabolic disorders. This chemical is Dichloroacetate (DCA), and it turns cancer into an angsty, suicidal teenager… the drug must go through the laborious, sisyphic and prohibitively expensive (~ $800m) process of gaining FDA approval. In the case of a drug that needs to be tested on nearly every single type of cancer the process would run into the multiple billions.
This means that no pharmaceutical company is going to get this drug FDA approved, especially since it also makes some of their less effective patented drugs worthless. As a matter of fact, they’ll probably lobby against it with all their might.
But never forget about a possible post-reaction just like in this case as Respectful Insolence commented the story (without using a beta-blocker): Dichloroacetate: One last time… But he writes in the original article that:
So where do I put on my pharma shill hat? Patience, dear readers… This drug has only been tested in cell culture and rats. Yes, the results were promising there, but that does not–I repeat, does not– mean the results will translate to humans.
I’ll follow the reply posts on the subject and will let you know when something important happens.
Update from the comments:
Update of the update:
Update of September:
- Health Canada has approved the first human trial of an experimental cancer drug called dichloroacetate, or DCA, in people with an advanced form of an aggressive brain cancer.
Update of October:
- Dichloroacetate (DCA) Phase II Trial To Begin (Terra Sigillata)
As far as I’m concerned it’s pretty irresponsible to say that DCA is a miracle (according to other blogs and articles on the web), especially without any human test results. I’m not a cancer expert, but I think that - as in many research fields, in pharmacy as well - without any acceptable and authentic evidence - in this case that would be long lasting and as mentioned expensive human drug experiments - it’s just Dr. Michelakis way to make a big splash. (Maybe he’s just competing to Nobel price
)
Another interesting fact is not mentioned in the most articles. DCA can cause pain, numbness and gait disturbances in some patients.
Actually, you’re right. By the way, Orac writes
Those of us who’ve been in the cancer field a while know that all too common are drugs that kill tumors in the Petrie dish and in mice or rats but fail to be nearly as impressive when tested in humans.
I can’t find anything on the human effects of DCA. Where did you find those (pain, numbness…)?
http://en.wikipedia.org/wiki/Dichloroacetic_acid#Adverse_effects
I didn’t read it first on wiki, but i couldn’t find the original link, it was some sort of science site.
Thank you for the link! Greg, don’t you have a blog? I’d really be curious about your opinions, comments on the world’s things.
Your welcome. Answering your question, I had a blog but it wasn’t too succesful. Maybe the opinions of an engineer student aren’t so interesting. Or I shouldn’t have written it in hungarian. (I like picking the latter reason, that saves me from beeing totally miserable
) Sad story, broke my hearth, you’ll never know how great author I am. 
Try the link to the main info page.
http://www.depmed.ualberta.ca/dca/
the original article in the journal Cancer Cell, warning, it is information dense. After reading it, it seems highly legitimate, but needs to be replicated, and then trials on patients run to confirm.
Uh, thanks for the link! I’ll definitely take a deeper look at it today.
work by Stacpoole indicates that toxicity is probably linked to thiamine deficiencies. Possible other toxicities at higher doses to liver function relate to methionine deficiencies, and resulting DNA hypomethylation. Dose level seems to be critical, yet the doses for safe usage are known since it is commonly used for other conditions which cause lactic acidosis. Whether it works will only be determined by treatment of individuals with cancer. Many will have no hope left, so have nothing to lose.
Yes, that’s not gonna happen in 10 years’ time… So even if it works, we won’t know about it.
what are the side effects to DCA could you please elaborate on pain, numbness and gait
You seem to have taken the letter writer’s statement as fact. Actually DCA has been used in treatment since the 1970s for metabolic disorders in children. Cancer research with Dichloroacetate has so far only been conducted in-vitro, but since the drug has been available for so long, I would expect that to change rapidly.
For information on it’s use see:
http://www.stanford.edu/group/hopes/treatmts/ebuffer/j4.html
Thank you for the link, this is the best review I’ve read on the subject.
Dose and duration are likely critical factors with respect to DCA side effects in humans.
I wrote an article about DCA and found two recent studies with conflicting results regarding DCA-induced peripheral neuropathy.
Stacpoole et al. (Pediatrics, 2006) ran a double-blind, randomized, control study of DCA in congenital lactic acidosis for 6 months using 25mg/kg/day and reported that oral DCA was well tolerated. However, Kaufmann et al. (Neurology, 2006) ended a 3-year cross-over clinical trial evaluating the efficacy of DCA in MELAS using 25mg/kg/day early due to peripheral nerve toxicity.
A study published last month (Felitsyn et al., J Neurochem, 2007) using cultured rat Schwann cells and dorsal root ganglia neurons found that DCA caused a dose- and exposure-dependent decrease of myelination, which may account in part for DCA’s clinical peripheral neuropathic effects.
It’s time to update the article, thanks for sharing this…
I have been giving my sister in law dca for 2 weeks. She seemed to be getting a little better. She has 4th stage cancer. But today she was in a lot of pain and we noticed blood in her urine.
Has anybody heard of this side affect if it is caused by dca or not.
I was giviang her 250 mg 2 times a day and incfeased it on Sunday (3 days ago) to 3 times a day. Please e-mail any info to tristarmarketing@aol.com
Toni
I sent an e-mail to you…
HI,
I would like to know more about the efficacy and therapeutic effects of dichloroacetate. can it be adminstered along with chemotherapy for endometrial stromal sarcoma(high grade).
As just a medical student, I only can show you some interesting and relevant links on the subject:
* Dichloroacetate safety
* DCA Research Information
* Wikipedia
I hope that any of them could help.
please send me any information on the use of dca where to purchase it . what dosage is recommended etc.
I came across this blog quite by chance but it made be very happy that there are decent folk about just trying to help others on the internet and not looking for anything lese other than a thank you! So thanks to you all and God Bless any of you who have relatives afflicted with Cancer. Really interesting stuff on this DCA.
Dear Bill, these words assure my that I’m doing my job right. Thank you very much!
and how doesn´t want a Nobel, justified, preze?
http://www.newscientist.com/channel/health/mg19325874.700-cheap-safe-drug-kills-most-cancers.html
The above url is the site that refers to side effects of dichloroacetate.
Is anyone familiar with Graviola or N-tense for treating cancers?
hsibaltimore.com has some info. It is sold by http://www.raintreenutrition.com
Hope this helps someone.
There is also the Great Physician, Jesus Christ, who can heal anything!! Get to know Him!
On March 18, 2007, my beloved wife died at home from metastatic breast cancer. I watched her last 4 hours and saw, heard and winessed her last breath. I do not know whether DCA would have helped 2 years ago, but I know that my wife and I would have tried the drug… Please continue your good work and keep hammering at the doors of the FDA… The oil and drug industry own us all,making billions of profit through lies, deceit, fraud and price gouging. the oil and drug industries are the Bobsie twins.
Thank you for telling us your story, Michael! I’m trying to find relevant and new information about this drug.
ko pienso de que esta droga debe tener algun efecto secundario que puede destruir las mismas celulas.
Since DCA has been in use for metabolic disorders it might be worth looking to see if there is a lower incidence of cancer in the group that has been taking it compared to the general population. This may give a hunch as to whether it also works in humans. There are obvious caveats nonetheless the information may already be available.
It’s interesting what you’re saying. I have to take a deeper look at it to find something relevant.
I’m living at Slovakia and we try the DCA at brain cancer,at pancreas cancer and at goot cancer. The tumor in brain during two weeks of using of DCA in dichloracetatesodium salt, 25 mg / kg diminished of 15 %. Such a diminishing never ocured at any chemo or radiotherapy! At other two cases the control tests will be finished at the beginning of june I shall report again.
Wow! That’s interesting. Would you please make contact with me via e-mail? I’d like to ask you some questions berci.mesko [at] gmail.com
Thank you in advance!
I have a patient with advanced prostate cancer. No other acceptable treatments, he is going to die. Understands this, and also understands possible consequences of DCA, and willing to trial it. 75kg body weight, will give him 30 mg per kg so 2.25 grams per day.
Once daily, twice daily ???
How long to continue for ???
Until side effects, until cured, until notice no change ???.
We have tried a lot of other natural therapies, no good. Last one was selenium ivi for 12 doses over 3 weeks. No change, tests still lousy and still in pain. Hopefully DCA will help.
Can someone let me know the above questions? Thankyou so much.
I think this site answers your questions: http://thedcasite.com/dca_dosage.html
My wife - the heart of my heart - has lung, liver, bone, and lymph nodes cancer. Ordered DCA today May 21,07. Will be here Friday. Will start Saturday morning. Starts radiation within 2 weeks; when she is strong enough she will start chemo. Will this drug be adequate during radiation and chemo…. If anybody has any answers please help me. Thank you. Will keep you briefed.
Dear Tony,
DCA is the chemotherapy itself. I haven’t found any relevant information about DCA and radiotherapy, but if there is, it must be found on this site: http://thedcasite.com.
I hope it helps.
We’re with you and your wife!
Question are there any anti oxidents in Dichoroacetate.The Radiation Oncology told me , to avoid any anti-oxidents while taking Radiation. can anyone answer this Question thank you
Tony, I think you should take a look at it: http://tinyurl.com/yo3unh
I’m glad to know that you have explored DCA in relation to cancer cure. I’m personally interested in these developments as one member of my family has cancer recurrence. I have written about it in my blog back in February 2007, although it was more of a brief note and pointing to information sites about it as I have no actual experience with it with patients. I’m hopeful about this development if only the potentially harmful side effects could be controlled.
Tony, I am a member of the discussion forum at the DCA site. I have taken the liberty to post your question on DCA/antioxidants in relation to radiotherapy. I hope we get a comment or a thought soon. Keep the hope going!
All the best.
K
Here is a reply from the forum in DCA site regarding the use of DCA during radiotherapy.
http://www.thedcasite.com/dcaforum/DCForumID1/55.html
Can the supposed side-effects of DCA usage (pain,numbness,etc) be worse the ones due to chemo, radio or brachytherapy?
Even if there is a semblance of hope from curing cancer the DCA way, I will be more than willing to volunteer. What’s the worst that testing DCA can do against not using it and letting cancer do it?!
Appreciate if anyone can let me know commonly used products that have DCA it them.
I think you’ll find answers here:
* Human Studies: http://tinyurl.com/yud2kx
* DCA Safety: http://tinyurl.com/2486ug
I realize that Dr. Michelakis and his team at Alberta have more or less designated DCA as “theirs” or “his,” but I believe that studies and discovery of DCA happened long before rumor of DCA as a possible cancer treatment began circulation (among others, I know Dr. Stacpoole at UF has been doing extensive research with DCA- possibly even developed it- for decades. I haven’t found direct cancer related studies that he has done YET, but I seem to remember hearing some being rumored as either in process or in proposal).
I understand and am sensitive to the fact that this could very well be an extremely important breakthrough for cancer patients, and I hope that it turns out to be as good as anyone could hope, but I am also aware of others in the medical community who seem a bit hesitant to glorify DCA to such an extent so soon. I can speak for no one but myself, but the media attention and the way that this has been put into public light so forcefully and so soon makes me a little uneasy. I appreciate that some believe that some hope is better than no hope at all, but is it right to advertise it in such a way as this? There’s a fine line of moral thoughtfulness and global repercussion when one is offering what seems to be more than just a glimmer of hope -indeed a possible cure- for something on such great a scheme as cancer. More studies need to be done, and that’s just it. Personally, I have enough hope in humanity that, be it cheap like DCA or not, the human community will find a way to make whatever cure surfaces to be accessible. So for me, that is not the immediate problem at hand. Sure, DCA might very well be a wonder drug; it might not. Time can seem incredibly cruel when something like this is tethered in front of so many in need, and I’m not at all to say that people shouldn’t try to take things into their own hands, but I can only hope that the only information read will be more than just what tells us what we want to hear- there’s a lot of talk of the same possibility, but it seems that skepticism becomes all to easily secondary.
I hope that DCA is truly a leap towards a cure. If it is, then all of the attention that Dr. Michelakis has drawn for himself will not be in vain for all of those who now hang their hopes upon the fruit of his esteem.
You’re absolutely right (I mean absolutely!), that’s why I tried to be neutral in the article. Thank you for the valuable comment!
The cure for cancer is ANTIBODIES.
A modified version of Dr. Donald L. Morton’s BCG treatment for bladder cancer will probably work in most cases. Here it is:
A single CC of old-style (aqueous) tuberculin has to be injected into the tumour of a tuberculin-positive patient. That means, the patient must first have been vaccinated against TB. The tuberculin causes the tumour to become swollen, because of the immune reaction. IF OTHER TUMOURS OR METASTASES BECOME INFLAMED IN SYMPATHY, THE PATIENT IS CURED. Such inflammation can only be due to cancer antibodies.
It is a cure because that variety of cancer will not come back.
Another variant is to add new-style (alcohol-soluble) tuberculin to the old-style. This “marker” will not wash away so quickly, giving the immune system more time to latch on.
As with the Morton bladder-cancer treatment, it may be repeated once a week for six weeks.
Dichloroacetate may indeed be a successful treatment. There is a paucity of information on the subject. However, it is strictly a form of chemotherapy.
Whenever a treatment extends the life of the patient, it allows the immune system time to “latch on” to the oncoprotein. Every cancer has altered DNA, and altered DNA produces altered protein - the oncoprotein. If dichloroacetate kills cancer cells, it is likely that whilst the immune system is cleaning up the debris, it might make the appropriate antibody.
There is an excellent description of the workings of the immune system in “Lamarck’s Signature” (Professor Ted Steele et al.).
Charles Douglas Wehner
My name is Kim. My dad was diagnosed with Lung Cancer 4 months ago. He has had 6 radiation treatments, which shrunk the tumor by half. This past Monday he started a round of chemo. I can only hope and pray that he will get better. Any information on DCA or any other drug that may help my dad and many others out there fighting off this awful disease would be so greatly appreciated.
09/27/07
Below as information for those following the DCA issue.
EDMONTON - Health Canada has approved the first human trial of an experimental cancer drug called dichloroacetate, or DCA, in people with an advanced form of an aggressive brain cancer.
Shannon Montgomery, THE CANADIAN PRESS
The molecule has drawn international attention after the University of Alberta’s Dr. Evangelos Michelakis published promising results in January showing it significantly shrunk tumours in rats. This new trial will give doctors a clue as to whether the research’s impressive results will make the jump into human subjects.
“Typically from the time you report results in animals to the point that you test in a human being, takes about three years, even with the support of the pharmaceutical industry,” Michelakis said Wednesday. “For us to have completed it in eight months is remarkable.”
Researchers hope to try the drug on up to 50 people with glioblastomas over the next 18 months. Michelakis said they are recruiting from the Edmonton area to start, but aren’t ruling out allowing people from other provinces to take part, as long as the funding can be found. The first subjects could begin within a few weeks.
http://healthandfitness.sympatico.msn.ca/
Thank you, Jim, I update the article.
Dear Kim, as a medical student, I can only show you some relevant links on the subject:
* Dichloroacetate safety
* DCA Research Information
* Wikipedia
I hope your father will get better soon!
Hi I’m a Type-1 diabetic. Has anyone tried Methylglyoxal, Acai Berries, Green Tea catchecins, and DCA in combination? While researching AGEs and Diabetic conditions I came across an interesting site.
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Indian Cancer Solution “Methylglyoxal”
Indian cancer researchers have taken a giant step on the road to discovering a solution for cancer by developing a drug that selectively targets the cancer cells without harming the healthy ones.
Researchers in Kolkata claim that patients in “very advanced stages” of cancer for whom all other treatments had failed have been brought back to “excellent” health with the help of a drug formulation they have developed after research spanning more than a decade.
“We have what we think magic bullet against cancer,” says Manju Ray, a biochemist at the Indian Association of the Cultivation of Science (IACS) where the drug was developed under a project funded by the Department of Science and Technology and the Council of Scientific and Industrial Research.
Most currently available anti-cancer drugs are toxic because they also damage the normal cells. Ray says the IACS formulation, containing “Methylglyoxal” as the lead ingredient, combats only the diseased cells, the cherished goal of cancer researchers worldwide. Methylglyoxal is a metabolite in the human body produced during glucose breakdown.
Others involved in the project are Swapna Ghosh of IACS, Manoj Kar and Subhankar Ray of the University College of Science, and Santajit Datta, a medical practitioner. Results of human trial conducted by them with the new drug have recently appeared in the Indian Journal of Physics.
While Americans are going ga-ga with their new anticancer drug “Glivec” - that was featured on the cover of May 28 issue of Time magazine - the low-profile, cash-strapped Kolkata researchers have been working quietly for over a decade shunning publicity until they obtained proof from human trials nine weeks ago.
According to their published paper, the Methylglyoxal-based formulation had “a dramatic positive effect on the patients”.
For instance, the condition of 11 out of the 19 patients treated - most of them in a very advanced stage when the treatment began — are now stated to be in “excellent physical condition”. Five are in stable condition and only three died during the course of the study.
Since the submission of the paper, the number of patients treated has crossed 40 mark with more than 70 per cent success, according to Manju Ray.
Most remarkable fact, according to the scientists was that Methylglyoxal was successful against different types of cancer unlike “Glivec” which targets only the chronic myeloid leukemia.
Those whose health returned to “excellent” condition after treatment with Methylglyoxal included patients in “a very advanced stages” of colon cancer, acute myeloid leukemia, non-Hodgkin’s lymphoma, and cancers of ovary, breast, liver, lung, bone, gall bladder, pancreas and oral cavity.
The patients were inducted for the trial, from January to June 2000, after obtaining permission from the Drug Controller General of India, the scientists said. The drug was administered orally for about six months with gradual reduction of daily dosage from the initial 25 milligrams per kilogram of body weight.
Researchers said development of the drug was preceded by years of basic research involving human cancer cells in culture and animal experiments that showed that Methylglyoxal selectively killed the cancer cells without affecting normal cells by exploiting “a very significant” biochemical difference between the two.
Explaining the mechanism of action, the scientists said cancer cells required a large amount of energy providing substance called ATP (Adenosine-5-Triphosphate) for survival.
“Methylglyoxal inactivates the enzyme (Glyceraldehyde-3- Phosphate Dehydrogenase) needed for ATP production in cancer cells and thereby starves them to death. Normal cells remain unaffected.”
Manju ray said that chemists knew Methylglyoxal molecule for about four decades and its anticancer effects in animals had also been studied. “But surprisingly, no one bothered to initiate further research leading to human trials,” she said.
The researchers said concern in some quarters about safety of Methylglyoxal were not borne out from the clinical trials, which showed that in combination with protective agent like Ascorbic Acid and vitamins, the drug Methylglyoxal had no major toxic effect.
They said there was scope for further enhancing the drug’s efficacy.
Hindustan Times Hyderabaad May 28, 2001
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http://www.biochemj.org/bj/323/0343/bj3230343.htm
Brazilian berry destroys cancer cells in lab, UF study shows
Filed under Research, Health, Sciences, Agriculture on Thursday, January 12, 2006.
GAINESVILLE, Fla. — A Brazilian berry popular in health food contains antioxidants that destroyed cultured human cancer cells in a recent University of Florida study, one of the first to investigate the fruit’s purported benefits.
Published today in the Journal of Agricultural and Food Chemistry, the study showed extracts from acai (ah-SAH’-ee) berries triggered a self-destruct response in up to 86 percent of leukemia cells tested, said Stephen Talcott, an assistant professor with UF’s Institute of Food and Agricultural Sciences.
“Acai berries are already considered one of the richest fruit sources of antioxidants,” Talcott said. “This study was an important step toward learning what people may gain from using beverages, dietary supplements or other products made with the berries.”
He cautioned that the study, funded by UF sources, was not intended to show whether compounds found in acai berries could prevent leukemia in people.
“This was only a cell-culture model and we don’t want to give anyone false hope,” Talcott said. “We are encouraged by the findings, however. Compounds that show good activity against cancer cells in a model system are most likely to have beneficial effects in our bodies.”
http://news.ufl.edu/2006/01/12/berries/
I noticed Inositols (IP-6) is good and can be added to the list above:
IP-6 Research Update
Inositol hexaphosphate ( IP6 ): a novel treatment for pancreatic cancer.
J Surg Res. 2005 Jun 15;126(2):199-203. Somasundar P, Riggs DR, Jackson BJ, Cunningham C, Vona-Davis L, McFadden DW.
Louis A. Johnson VA Medical Center, Clarksburg, West Virginia; Department of Surgery, West Virginia University, Morgantown, West Virginia, USA.
Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate found in food sources high in fiber content. IP6 has been reported to have significant inhibitory effects against a variety of primary tumors including breast and colon. The effects of IP6 have not been evaluated in pancreatic cancer. We hypothesized that IP6 would significantly inhibit cell growth and increase the apoptotic rate of pancreatic cancer in vitro.
CONCLUSIONS: Treatment of pancreatic cancer with the common dietary polyphosphorylated carbohydrate IP6 significantly decreased cellular growth and increased apoptosis. Our findings suggest that IP6 has the potential to become an effective adjunct for pancreatic cancer treatment. Further in vivo and human studies are needed to evaluate safety and clinical utility of this agent in patients with pancreatic cancer.
Caveat: Do not take SAMe or methylating factors if you already have cancer. The above study was done on animals, and pertains only to liver cancer. While it appears certain that methylation-enhancement will prevent cancer from starting, and while it looks very promising in liver cancer, not enough research has been done to show what happens when methylation-enhancing factors are taken during cancer. Most cancers are methionine-dependent. Patients with cancer should never take supplemental methionine.
Methylation and Homocysteine
SAMe is created in the body from methionine and ATP. When SAMe is used for methylation, a chemical reaction occurs where a methyl group is lost, and a by-product is created. This by-product is homocysteine. Homocysteine has gotten a lot of press recently as a culprit in heart attack and stroke. But homocysteine is not a bad thing in and of itself. Only when it’s allowed to accumulate does it start trouble.
If things are going as they’re supposed to, homocysteine is converted to glutathione, a natural antioxidant, or back to methionine. If not converted, homocysteine can inhibit methylation.
Elevated homocysteine causes lipid peroxidation and sticky platelets, both of which are associated with oxidation. It has been recently discovered that pigs with elevated homocysteine have abnormally high iron levels in heart muscle. Iron promotes free radical formation.
Free radicals are not all bad. The body generates them for certain things. Surprising new research shows that homocysteine may help the immune system create the free radicals it uses to fight off invaders. Apparently, a gene that provokes the death of defective cells (apoptosis) begins the “destruct” process by increasing levels of homocysteine.
There is some evidence that oxidative stress may impede methylation, and anything that reduces oxidative stress may enhance methylation. Researchers in Italy found that free radicals greatly reduce the synthesis of proteins, including lipoproteins. They attribute the decreased synthesis to under-methylation. Methylation is critical for protein synthesis, including the synthesis of lipoproteins such as cholesterol.
Vitamins Lower Homocysteine
The natural detoxification of homocysteine can happen only if enough B-vitamins are present. In order to convert homocysteine to glutathione, sufficient vitamin B6 must be present. In order to convert it to methionine, there must be enough folate and vitamin B12. These vitamins, along with TMG (trimethylglycine) which can also lower homocysteine, are called “methylating factors” because they increase SAMe and enhance methylation.
Unfortunately, the American fast-food, meat-based diet is rich in methionine (meat) and poor in B vitamins (vegetables). The best sources of vitamin B6 and folate are unfrozen, uncanned vegetables and grains. Without the crucial B vitamins, homocysteine becomes a problem. High doses of certain vitamins decrease homocysteine by as much as 55 percent, according to a recent study published in Arteriosclerosis, Thrombosis and Vascular Biology.
Methylation Deficiencies
A person can’t go out and have his or her methylation measured. But the effects of under-methylation can be seen as premature aging, cancer, heart disease, liver disease and other chronic illness, depression and birth defects.
Just as the body can become depleted of antioxidants, it can become methylation-depleted. Since SAMe is the number-one methylation substance, anything that depletes SAMe lowers methylation. Anything that interferes with the synthesis of ATP (such as alcohol) will deplete SAMe, as will aging. Lack of vitamins B6, B12 and folic acid will eventually deplete SAMe, and so will unusual demand.
Aging decreases SAMe. As with free radicals, once under-methylation begins, it can snowball into a monster. All sorts of bad things can happen, from broken DNA to cancer, which brings up an important point.
http://www.lef.org/magazine/mag98/aug98-report2.html
http://www.arrowheadhealthworks.com/methgly.htm
Many articles here on methylglyoxal and Cancer.
Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy.
Nat Med 2003 Mar; 9(3): 294-9.
Hammes HP, Du X, Edelstein D, Taguchi T, Matsumura T, Ju Q, Lin J, Bierhaus A, Nawroth P, Hannak D, Neumaier M, Bergfeld R, Giardino I, Brownlee M.
Three of the major biochemical pathways implicated in the pathogenesis of hyperglycemia induced vascular damage (the hexosamine pathway, the advanced glycation end product (AGE) formation pathway and the diacylglycerol (DAG)-protein kinase C (PKC) pathway) are activated by increased availability of the glycolytic metabolites glyceraldehyde-3-phosphate and fructose-6-phosphate. We have discovered that the lipid-soluble thiamine derivative benfotiamine can inhibit these three pathways, as well as hyperglycemia-associated NF-kappaB activation, by activating the pentose phosphate pathway enzyme transketolase, which converts glyceraldehyde-3-phosphate and fructose-6-phosphate into pentose-5-phosphates and other sugars. In retinas of diabetic animals, benfotiamine treatment inhibited these three pathways and NF-kappaB activation by activating transketolase, and also prevented experimental diabetic retinopathy. The ability of benfotiamine to inhibit three major pathways simultaneously might be clinically useful in preventing the development and progression of diabetic complications.
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More results of the methlyglyoxal treatments with several B vitamins
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http://www.kanker-actueel.nl/sitemap/res_ca_nu.methylglyoxal.html
Additional functions
GAPDH is multifunctional like an increasing number of enzymes. In addition to catalysing the 6th step of glycolysis, recent evidence implicates GAPDH in other cellular processes. This came as a surprise to researchers but it makes evolutionary sense to re-use and adapt an existing proteins instead of evolving a novel protein from scratch.
[edit] Transcription and apoptosis
Zheng et al. discovered in 2003 that GAPDH can itself activate transcription. The OCA-S transcriptional coactivator complex contains GAPDH and lactate dehydrogenase, two protein previously only thought to be involved in metabolism. GAPDH moves between the cytosol and the nucleus and may thus link the metabolic state to gene transcription. [1]
In 2005, Hara et al. showed that GAPDH initiates apoptosis. This is not a third function, but can be seen as an activity mediated by GAPDH binding to DNA like in transcription activation, discussed above. The study demonstrated that GAPDH is S-nitrosylated by NO in response to cell stress, which causes it to bind to the protein Siah1, a ubiquitin ligase. The complex moves into the nucleus where Siah1 targets nuclear proteins for degradation, thus initiating controlled cell shutdown. [2] In subsequent study the group demonstrated that deprenyl, which has been used clinically to treat Parkinson’s disease, strongly reduces the apoptotic action of GAPDH by preventing its S-nitrosylation and might thus be used as a drug. [3]
ER to Golgi transport
GAPDH also appears to be involved in the vesicle transport from the endoplasmic reticulum (ER) to the Golgi apparatus which is part of shipping route for secreted proteins. It was found that GAPDH is recruited by rab2 to the vesicular-tubular clusters of the ER where it helps to form COP 1 vesicles. GAPDH is activated via tyrosine phosphorylation by Src. [4]
Cellular location
All steps of glycolysis take place in the cytosol and so does the reaction catalysed by GAPDH. Research in red blood cells indicates that GAPDH and several other glycolytic enzymes assemble in complexes on the inside of the cell membrane. The process appears to be regulated by phosphorylation and oxygenation. [5] Bringing several glycolytic enzymes close to each other is expected to greatly increased the overall speed of glucose breakdown.
http://en.wikipedia.org/wiki/Glyceraldehyde_3-phosphate_dehydrogenase
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Take Deprenel?
Mech Ageing Dev 2002 Apr;123(8):1087-100
Why (-)Deprenyl prolongs survivals of experimental animals: Increase of anti-oxidant enzymes in brain and other body tissues as well as mobilization of various humoral factors may lead to systemic anti-aging effects.
Kitani K, Minami C, Isobe K, Maehara K, Kanai S, Ivy GO, Carrillo MC.
National Institute for Longevity Sciences, 36-3, Gengo, Morioka-cho, Obu-shi, 474-8522, Aichi, Japan.
(-)Deprenyl, a monoamine oxidase B (MAO B) inhibitor is known to upregulate activities of anti-oxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) in brain dopaminergic regions. The drug is also the sole chemical which has been repeatedly shown to increase life spans of several animal species including rats, mice, hamsters and dogs. Further, the drug was recently found to enhance anti-oxidant enzyme activities not only in brain dopaminergic regions but also in extra-brain tissues such as the heart, kidneys, adrenal glands and the spleen. We and others have also observed mobilization of many humoral factors (interferone (INF)-gamma, tumor necrosis factor (TNF)-alpha, interleukine (IL)-1beta,2,6, trophic factors, etc.) and enhancement of natural killer (NK) cell functions by (-)Deprenyl administration. An apparent extension of life spans of experimental animals reported in the past may be better explained by these new observations that (-)Deprenyl upregulate SOD and CAT activities not only in the brain but also in extra-brain vital organs and involve anti-tumorigenic as well as immunomodulatory effect as well. These combined drug effects may lead to the protection of the homeostatic regulations of the neuro-immuno-endocrine axis of an organism against aging.
http://www.anti-aging-guide.com/51deprenyl.php
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July 31, 2007
From http://www.erieblogs.com/archives/2007/07/
Inventor John Kanzius will share the latest updates on his groundbreaking cancer research project to area business and community leaders, during the Manufacturers’ Association’s monthly Eggs ‘n’ Issues briefing, Tuesday, July 31, at the Manufacturers’ Association of Northwest Pennsylvania (http://www.manp.org/) Conference Center, 2171 West 38th Street at 8 am.
The Kanzius Non-invasive Radio Wave Treatment is a potential cancer therapy that uses high-energy radio waves to destroy cancer cells that have been “tagged” with nano particles. Nano particles attached to cancer cells are heated by radio waves to a temperature, which destroys the cancer cells. The technique is non-invasive, and can be provided without the need for auxiliary chemotherapy or radiation. Intensive and promising technological research about the Kanzius Radio wave Treatment is currently under way at M. D. Anderson Cancer Center in Houston, Texas, the University of Pittsburgh Medical Center, the Mayo Clinic and other American medical centers.
http://youtube.com/watch?v=h6vSxR6UKFM
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On Oct. 5, 2007, John said that “the largest research centers and nanoscientists in the world” are involved in this project.
[edit]Inventor: John Kanzius
Sanibel Island [Florida] resident John Kanzius is a former broadcast executive from Pennsylvania who wondered if his background in physics and radio could come in handy in treating the disease from which he suffers: cancer. A person witnessing the device asked him if it might desalinate water. When he ran an experiment using a test tube of salt water, the water began to burn.
John Kanzius’ primary interest is in using this radio frequency nanotechnology to cure cancer. This Hydrogen-from-Salt Water discovery is but an interesting if not annoying detour for him.
He invites interested parties to visit their lab to see a demonstration of the technology.
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http://news.google.com/news?&q=kanzius
Stimulation of Suicidal Erythrocyte Death by Methylglyoxal
Jan Nicolay1, Juliane Schneider1, Olivier Niemoeller1, Ferruh Artunc1, Manuel Portero-Otin2, George Haik Jr.3, Paul Thornalley2, Erwin Schleicher4, Thomas Wieder1, Florian Lang1
1Department of Physiology, and
4Department of Internal Medicine, University of Tübingen,
2Department of Biological Sciences, University of Essex,
3George Haik Eye Clinic, New Orleans, Louisiana
Address of Corresponding Author
Cellular Physiology and Biochemistry 2006;18:223-232 (DOI: 10.1159/000097669)
goto top of page Abstract
Diabetes increases the percentage of circulating erythrocytes exposing phosphatidylserine (PS) at the cell surface. PS-exposing erythrocytes are recognized, bound, engulfed and degraded by macrophages. Thus, PS exposure, a feature of suicidal erythrocyte death or eryptosis, accelerates clearance of affected erythrocytes from circulating blood. Moreover, PS-exposing erythrocytes bind to the vascular wall thus interfering with microcirculation. The present study explored mechanisms involved in the triggering of PS exposure by methylgloxal, an extra- and intracellular metabolite which is enhanced in diabetes. PS exposure, cell size and cytosolic Ca2+-activity after methylglyoxal treatment were measured by FACS analysis of annexin V binding, forward scatter and Fluo-3-fluorescence, respectively, and it was shown that the treatment significantly enhanced the percentage of PS-exposing erythrocytes at concentrations (0.3 µM) encountered in diabetic patients. Surprisingly, methylglyoxal did not significantly increase cytosolic Ca2+ concentration, and at concentrations up to 3 µM, did not decrease the forward scatter. Instead, exposure to methylglyoxal inhibited glycolysis thus decreasing ATP and GSH concentrations. In conclusion, methylglyoxal impairs energy production and anti-oxidative defense, effects contributing to the enhanced PS exposure of circulating erythrocytes and eventually resulting in anemia and deranged microcirculation.
Copyright © 2006 S. Karger AG, Basel
http://content.karger.com/ProdukteDB/
produkte.asp?Aktion=ShowAbstract
&ProduktNr=224332&Ausgabe=232685&ArtikelNr=97669
[Implication of methylglyoxal in diabetes mellitus]
[Article in Romanian]
Artenie A, Artenie R, Ungureanu D, Haulică I, Artenie V.
Clinica a IV-a Medicală, Spitalul Clinic nr.2 C.I. Parhon Iaşi.
Methylglyoxal (MG) is an early glycation product which is implicated in genesis of diabetic complications either as a direct toxin or as a precursor for advanced glycation end products. It is metabolized via S-D-lactoylglutathione to D-lactate by means of the enzymes glyoxalase I and II, which depend on glutattione as cofactor. MG is highly reactive and can bind to and modify proteins by chemical interaction with cellular proteins, action on energy production, induce free radical generation and cell killing. That way MG play a role in the events of the development of diabetic complications.
http://www.ncbi.nlm.nih.gov/sites/entrez?
Db=PubMed&Cmd=ShowDetailView&TermToSearch=
14756009&ordinalpos=1&itool=EntrezSystem2.
PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus
I won’t lose hope. I hope more and more extensive follow up studies and tests shall follow through. This may not be the ultimate cure for now but at least the persons behind this cancer messiah already did a great initial step towards curing cancer.
There will never be an ultimate cure for cancer. All types of cancers must be treated in an individualized way. That’s why personalized medicine has a great future.
Do you feel bad now for recommending that DCA vendor site to those desperate people who read your blog?
Why should I, Mr. Gunn?
Before rejecting this drug, I hope FDA people would take a look at its mechanism or potentials instead of the price that goes with it. Sometimes we get more if we pay more.
“Another year over-And a new one just begun” Anything that may look promising to assist or cure cancer-hey…sign me up! I’m sooo very tired of the toxins that go through my body during chemo. The medical community has discredited me for “asking” and “wanting” to know all that I can to make an informed decision, but have failed to satisfy or have gone as far as saying “I don’t have time” to answer those 3 questions (after making me wait 2 hours beyond my scheduled oncology appointment. I have had 3 oncologists for treatment over the past year. One who will order just about anything according to “standard regime”, no matter how it affects the patient, and then when things didn’t work out (severe allergic reaction for me), he wants to “continue” and in his own words “challenge me”. Thanks, but I want to live a little longer! Transferred to “new oncologist” who saw me a brief 2 visits over 8 months. She was either “too busy, on holidays, or on conference calls”, so was observed by her associates. After a brief encounter with a chemical (Oven Off), the Associate told me, the cancer was spreading! She made her sincere apologies. She informed me she could order a “chemo pill” as she has with a previous patient and is doing remarkably well now. No, I passed on the offer, went home and popped antihistimes all weekend. By Monday am, I was all better!!! I went back on the Friday and asked the oncologist “have you changed your mind about your diagnosis from last Friday?” She exclaimed “Absolutely! What did you do?” Well, I guess I cured my cancer with Antihistimines! maybe you should seek out that other female patient u spoke of and order her up some Antihistimines!
Forgive me her, but sometimes these Drs. are thinking of what now? The best interest of their patients? Or are they truly overwhelmed at “what might be available to offer as options?” Getting back to my 2nd oncologist, Since Aug of 07, small leisons on the chest wall (recurrance of IBC with surgery & 4xAC,1xTax, 3xAC & 10 Herceptin) has now developed into 8 tumors along the scar line underarm. Treatment:Took away Herceptin - Wait & See Approach! What???? So, now I’m working on/with new Oncologist. Consult ended with: Back to Herceptin starting immediately, and a new regime of Vinorelebine? I am totally frustrated, annoyed Scared to no end, and I just want to be “healthy” again. Cure will never be part of my vocabulary, but to have something, anything that will support otherwise a healthy body, is it out there??? This DCA - would have to be a small step beyond Antihistimines, wouldn’t ya think??? lol I would be more than happy to try anything that would not compromise or jepordize the healthier side of what we are going through! So please, keep on searching, pls don’t discredit one’s accomplishments. They are so far & few between. And I always try to remember this “a little bit of something, is a whole lot better than nothing”. God Bless to All! Fran
Hmmmmm, let’s see….side effects VS dying of cancer
To those who say “wait until the testing is complete and the FDA approves DCA,” I respond by saying:
On the day you are diagnosed with cancer and given a life expectancy of maybe 2 to 5 years, then and only then can you say wait. And when you start waiting, then and only then, can you START to develop your new cancer cure using an inexpensive, non-patentable chemical that shows incredibly good promise for curing cancer, but no possible hope of earning back even the tiniest fraction of the cost of studies required for FDA approval.
And by the way, while you’re waiting, you’re being pumped full of some of the most toxic chemicals known to man, and being bombarded with nearly lethal doses of radiation. You’re in pain or feel ill or are physically exhausted, experience sleep disorders, anxiety, depression, dehydration and untold other symptoms. But you get to keep waiting to even get the chance to try out your own cure while you’re trying to get the funding, organize and plan the studies… oh forget it… you’ll be long dead decades before your cure will ever come to market.
But at least you won’t have to wait anymore.