Cancer cure ,and nobody noticed,

[undergroundpanther]

http://www.depmed.ualberta.ca/dca/

[uppityperson]

1. Thank you, will be interesting to see what trials show.

we can hope for the best.

[DainBramaged]

2. It will have to be privately funded because drug companies can't make money on it

FDA testing is going to cost millions, so a lot of private funding is going to be necessary to perform trials.

[Trillo]

17. Fill me in on that.

What I read is that the pharmaceutical is already manufactured for another disorder, and has been for a long time.

Was that incorrect?

If it is available, it should be an easy and simple matter to find people for trials. If it's super expensive to do this, then somebody or a whole lotofbodys are getting ripped off. Guess who those people might be?

[DainBramaged]

18. Here

http://laughingsquid.com/dca-may-have-big-impact-on-the-fight-against-cancer/


The drug companies can't make money on a proven cheap drug, so they have no intention of funding research for it's use elsewhere.

[Trillo]

21. "Open-source" medical research.

That's an interesting concept.

Tinfoil time: I wonder about the U.S. government's continued failure to fund any medical research that might be cheap and inexpensive, and about the charges through the years that it either actively obfuscates or disrupts any research that might result in something "inexpensive", or fails to investigate such disruption allowing it to continue when it may be perpetrated by third-parties. It seems that with any income based taxation system, there's an inherent or structural incentive to increase others' expenses which in turn leads to increased taxation revenues.

Increasing the political process, or power of the political overseer, in every Department, as Bush has reportedly recently done through Executive Order, simply increases this distrust.

edited for comma usage.

[parasim]

3. and apparently no one cares...

One would think that what appears to be a potential cure for cancer would be front page news.

Hey, I got an idea, let's declare cancer cells terrorists.

Hell, we're currently pumping $6 billion a month into the War on Terror. Seems to me thecost of the human trials needed to prove this cure would be a drop in the bucket compared to that.

Or, maybe we could ask Bill Gates. You'd think he might be able to spare a billion or so to do the trials.

[babylonsister]

10. People care; I sent this to KO last week after it was posted on DU:

http://www.democraticunderground.com/discuss/duboard.php?az=show_topic&forum=389&topic_id=89859

Did Scientists CURE CANCER last week and nobody noticed?

Posted by matcom
<snip>

New Scientist has received an unprecedented amount of interest in this story from readers. If you would like up-to-date information on any plans for clinical trials of DCA in patients with cancer, or would like to donate towards a fund for such trials, please visit the site set up by the University of Alberta and the Alberta Cancer Board. We will also follow events closely and will report any progress as it happens.

It sounds almost too good to be true: a cheap and simple drug that kills almost all cancers by switching off their “immortality”. The drug, dichloroacetate (DCA), has already been used for years to treat rare metabolic disorders and so is known to be relatively safe.

It also has no patent, meaning it could be manufactured for a fraction of the cost of newly developed drugs.

Evangelos Michelakis of the University of Alberta in Edmonton, Canada, and his colleagues tested DCA on human cells cultured outside the body and found that it killed lung, breast and brain cancer cells, but not healthy cells. Tumours in rats deliberately infected with human cancer also shrank drastically when they were fed DCA-laced water for several weeks.

DCA attacks a unique feature of cancer cells: the fact that they make their energy throughout the main body of the cell, rather than in distinct organelles called mitochondria. This process, called glycolysis, is inefficient and uses up vast amounts of sugar.

<snip>

The next step is to run clinical trials of DCA in people with cancer. These may have to be funded by charities, universities and governments: pharmaceutical companies are unlikely to pay because they can’t make money on unpatented medicines. The pay-off is that if DCA does work, it will be easy to manufacture and dirt cheap.


more......

http://www.newscientist.com/article/dn10971-cheap-safe-...

[orleans]

4. i just read a rather lengthy article in new scientist about this. n/t

[Igel]

5. The New Scientist article, and link to abstract:

New Scientist link: 
http://www.newscientist.com/article/dn10971-cheap-safe-drug-kills-most-cancers.html


I can't get access to the article itself (not that I'd
understand it all)--the university I get to online journals
through doesn't have access to the last year's articles, and I
don't have a subscription (I'm a linguist)--but the summary
seems to imply that not all cancers are going to be as
affected.  I also don't know if I agree with what appears to
be their posited mechanism for oncogenesis: either New
Scientist got it wrong, I don't think they can really account
for oncogenesis.  If this is the case, DCA and its mimics
aren't cures, but treatments that reduce the size of tumors
and prevents metastasis.

------------------
Cancer Cell Volume 11, Issue 1 , January 2007, Pages 37-51
(doi:10.1016/j.ccr.2006.10.020)
A Mitochondria-K+ Channel Axis Is Suppressed in Cancer and Its
Normalization Promotes Apoptosis and Inhibits Cancer Growth 

Sébastien Bonnet1, Stephen L. Archer1, 2, Joan
Allalunis-Turner3, Alois Haromy1, Christian Beaulieu4, Richard
Thompson4, Christopher T. Lee5, Gary D. Lopaschuk5, 6, Lakshmi
Puttagunta7, Sandra Bonnet1, Gwyneth Harry1, Kyoko Hashimoto1,
Christopher J. Porter8, Miguel A. Andrade8, Bernard Thebaud1,
6 and Evangelos D. Michelakis1, ,  
<deleted affiliations .. all at Canadian institutions,
Alberta or Ottawa>

Received 25 November 2005;  revised 12 July 2006;  accepted 18
October 2006.  Published: January 15, 2007.  Available online
16 January 2007. 


Summary
The unique metabolic profile of cancer (aerobic glycolysis)
might confer apoptosis resistance and be therapeutically
targeted. Compared to normal cells, several human cancers have
high mitochondrial membrane potential (&#916;&#936;m)
and low expression of the K+ channel Kv1.5, both contributing
to apoptosis resistance. Dichloroacetate (DCA) inhibits
mitochondrial pyruvate dehydrogenase kinase (PDK), shifts
metabolism from glycolysis to glucose oxidation, decreases
&#916;&#936;m, increases mitochondrial H2O2, and
activates Kv channels in all cancer, but not normal, cells;
DCA upregulates Kv1.5 by an NFAT1-dependent mechanism. DCA
induces apoptosis, decreases proliferation, and inhibits tumor
growth, without apparent toxicity. Molecular inhibition of
PDK2 by siRNA mimics DCA. The mitochondria-NFAT-Kv axis and
PDK are important therapeutic targets in cancer; the orally
available DCA is a promising selective anticancer agent.

[mopinko]

6. people are not tissue cultures, or even mice

this treatment still has a long way to go before it can rightly be called a cure.

[Tom Joad]

7. very unlikely this is a "cancer cure". It may help in treatment of some cancers.

[Bruce McAuley]

8. Cheap and not patentable.

http://www.newscientist.com/channel/health/mg19325874.700-cheap-safe-drug-kills-most-cancers.html
I also did some checking around on availability.
It's not available from my local pharmacy.
It's not available on eBay.
It IS available from Chinese manufacturers, but dosage might be problematic.
It is a byproduct of other organochlorene manufacture, and can be reduced from trichloroacetate.
It has been given to humans for other illnesses, and has a track record.
I'm looking to acquire some just for the hell of it.

Bruce

[suziedemocrat]

12. Who is the woman in your Avatar?

A lot of people have that Avatar - and I've never known who it is.

Nevermind... found out .... Suzanna Arundhati Roy - Indian novelist, writer and activist. She won the Booker Prize in 1997 for her first novel, The God of Small Things, and, in 2002, the Lannan Cultural Freedom Prize.

p.s. - Great news on the cancer cure. There should be public funding for some of these FDA trails.

[and-justice-for-all]

9. Yeah, I noticed...

..Then I sent the story to a local NBC affiliate.

[Turn CO Blue]

11. Hard to say it will actually cure cancer in humans

just because it works on cells in a petrie dish or even if it works on mice.

Remember when they injected obese mice with the hormone Leptin and the mice quickly, consistently and dramatically lost all their excess weight, and then they did human trials and injected Leptin into obese humans and it had no affect whatsoever?

Anyway I do hope it does cure cancer -- my mother's death was painful and slow from lung cancer.

[Mayberry Machiavelli]

13. The idea that this will not even be researched because it can't be patented is absurd.

If it truly has as much promise as implied on the various DU threads related to this, it will be investigated.

http://www.democraticunderground.com/discuss/duboard.php?az=view_all&address=389x121845

[undergroundpanther]

14. Umm

Too many companies operate on a psychopathic model.
They won't research it unless it can be EXPLOITED.
The reason so many diseases are not cured but "maintained" is because of the PROFITS lie in maintaining a "health problem" generates VS 1 sale and maybe no repeat customers to make it profitable..
http://www.commondreams.org/views04/0218-01.htm
http://ponerology.blogspot.com/2006/01/ideologies-their-use-and-misuse-in.html

http://newint.org/features/2003/04/01/narcissim/

[Mayberry Machiavelli]

15. The point is, research does not require pharmaceutical companies. It is not a necessary

condition.

[A Simple Game]

16. Exactly why we need single payer health care.

It would be profitable to find a cure if the taxpayers were paying the bills.

[HiFructosePronSyrup]

20. Yeah.

The NCI continually operates a massive research project into this sort of thing.

Patentable or otherwise.

Shame it's got to turn into a big conspiracy theory.

[atommom]

19. This has been posted here before. It CAN be patented for a new use.

And yes, it may be promising, but this is very early in the game. Many drugs looked even better than this in initial trials, and then turned out not to be effective in humans. It's not getting a lot of MSM press because it's too early to say whether it will work on humans or not. To report on it now might raise false hope. I agree that there are many reasons to distrust big pharma, but in this particular case, I don't see anything fishy. Here is a piece about why the hysteria over this drug is overblown at this stage.


1. 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. In fact, most likely, they will not. 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. In the 1980's it was immunotherapy. Man, some immunotherapies totally melted tumors away but, sadly, didn't do nearly as well in human trials. The same is true of antiangiogenic therapy, pioneered by my surgical and scientific hero Judah Folkman. In 1998, it was all over the media (see pictures below) that antiangiogenic therapy would be the "cure" (or at least would turn cancer into a manageable chronic disease). These drugs dramatically shrank tumors in mice in two major studies published in Cell and even induced tumor dormancy, as described in Nature. Guess what? They didn't do the same thing in humans. Don't get me wrong, antiangiogenic drugs have proven to be a useful addition to our anticancer armamentarium (not to mention an area of research interest for me). However, remember the saying: "If it sounds too good to be true, it probably is." Well, it probably is in the case of DCA.

Mouse.jpgCancer.jpg

2. Cancer is not a single disease. It is many diseases, and requires many different approaches. This drug showed activity against several cancers in vitro, but there are conventional chemotherapeutic drugs that also show activity against lots of cancers. In fact, the comparison to antiangiogenics becomes even more relevant here, because antiangiogenic drugs theoretically could act against any cancer. That's because they target normal cells lining blood vessels, which are needed to grow new blood vessels to supply tumors with blood and oxygen. These cells are very stable, and much less prone to the mutations that cancer cells undergo with such frequency that can lead to resistance. In contrast. DCA targets the tumor cells themselves, which are far more likely to develop resistance. Bloggers ranting against big pharma are showing magical thinking in assuming that this drug will work against nearly all tumors, given that at best only 60-90% of cancers even demonstrate the Warburg effect. Indeed, remember how I mentioned that in this study DCA inhibited tumor growth by 60% or more in rats? Pretty impressive, yes? Compare this result to that obtained by angiostatin and endostatin, both of which melted experimental mouse tumors away to a few dormant cells. Neither were anywhere as impressive against human tumors. That doesn't mean antiangiogenics aren't useful cancer drugs (Bevicuzimab, in particular is quite effective at potentiating the effect of chemotherapy in colorectal cancer, for example), but they are useful in the same way that a number of chemotherapeutic agents are usefu: as an additional weapon. They are not miracle cures, and I'd be willing to bet that DCA isn't, either.

3. Here's where the worst misinformation is being spread about this story. It will not cost $600-800 million to do clinical trials to test this drug, yet certain bloggers are acting as if that much money will be needed to to see if this drug works in humans. That's just a load of crap. That figure refers to the total cost of bringing a new drug to market, from idea to research and development, to synthesis, to cell culture and animal studies, to patent applications, to all the clinical trials needed, to filing the regulatory documentation, all of which together can sometimes approach $1 billion. It does not refer to the amount of money required to do a clinical trial to see if there is efficacy in humans, the logical next step after what has been published thus far. In contrast to what's being spewed into the blogosphere, to run a preliminary trial to determine if there is evidence of efficacy in humans could be done for costs that are well within the means of an investigator, if he's willing to apply for grants. All he would require is a few hundred thousand dollars for a small preliminary trial (less ideal) or probably between $1 and $5 million for an intermediate-sized Phase II study against one tumor (it's the Phase III trials, with thousands of patients, that cost tens of millions of dollars). Most NIH R01 grants are funded for between $1 and $2 million (mine's for a little more than $1.3 million over 5 years), and clinical R01 grants can be funded for up to a few million dollars. Thus, this is not by any means an unreasonable amount of money to be trying raise to do the trial to confirm in humans the preclinical data and, if the effect is as great in humans as it is in animals, should be adequate to detect the drug's promise. If that turns out not to be a big enough sample, then that would imply either that (1) this drug isn't effective at all in humans or (2) isn't any more effective than many other conventional chemotherapeutics that we already have. True, the funding climate sucks these days, but Michelakis is funded by grants from the Canadian Institutes for Health Research (CIHR), Alberta Heritage Foundation for Medical Research (AHFMR), and Canadian Foundation for Innovation. He's perfectly free to apply to the NIH and other organizations for funding. Given such compelling preclinical data, hewould stand a very good chance of being funded.

4. Lastly, there was nothing stopping the investigator from patenting the idea of using DCA to treat cancer. I know someone who is doing just that for a use of a drug that's FDA-approved for treating something totally unrelated to cancer. indeed, I sincerely hope that Michelakis has, in fact, done this, because now that his results have published it's too late; the cat's out of the bag. If he had done that, he could then have licensed his idea to whatever pharmaceutical company was interested, and that pharmaceutical company would then have had a patent on the use of this drug to treat cancer. If Michelakis hasn't done that, well, I applaud his idealism (or curse his naïveté); he shot himself in the foot and made his idea less appealing to industry.

I'm not in any way saying that it isn't a problem that drug companies show little or no interest in potentially promising new compounds that they can't patent. It can be a problem, just as "orphan" drugs often don't make it to market because there aren't enough patients who could benefit from the them to make it profitable for drug companies to invest in developing and marketing them. In those cases, there are government programs to encourage the manufacture of these drugs. Perhaps a similar sort of program should be in place for situations like this or perhaps tax incentives to encourage pharmaceutical companies to manufacture drugs like this. Also, if this drug were truly the miracle cure that it's being represented as, believe me, pharmaceutical companies would find a way to make money off of it, either by trying to modify it to make it more effective or adding a molecule to target it more closely to the cancer cell.

more: http://scienceblogs.com/insolence/2007/01/in_which_my_words_will_be_misinterpreted.php

[Mayberry Machiavelli]

22. Thank you for this informative post. The issue of increasing reliance on private sector

funding of medical research vs. public, and difficulty funding research into orphan drugs, is very real, although I think the problem is less that Rx companies are spending more money on research (why would this be a problem) than that the government share of research money is stagnant (increased less than inflation this last year).

The points you bring up are good. Because one guy published one study, people seem to have taken leave of any skepticism: "It's the cure for cancer!" How many of THOSE have we had over the last few decades, whether it's antiangiogenesis drugs, immune modulating drugs, monoclonal antibodies and many more, all of which showed promise, none of which are "the cure for cancer" (which there will never be ONE because it's such a wide group of different diseases).

Because dichloroacetate has actually already undergone clinical trials in humans for treatment of mitochondrial disorders, some of the initial barriers to study of this drug are already crossed.

In my other thread which I linked elsewhere in this thread, there are examples of some of the trials, in humans, that have been done on DCA for mitochondrial diseases. They definitely show toxicity to the nerves, one of the pediatric studies was terminated due to nerve toxicity issues.

Of interest, DCA is actually known to be carcinogenic to the liver, at least in mice. Apparently the mouse exposure causing liver cancer is at higher levels than have been used in the clinical trials of DCA in humans:


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15036762&query_hl=1&itool=pubmed_docsum

1: Toxicology. 2004 Mar 1;196(1-2):127-36.Click here to read Links
Hypomethylation of DNA and the insulin-like growth factor-II gene in dichloroacetic and trichloroacetic acid-promoted mouse liver tumors.

* Tao L,
* Li Y,
* Kramer PM,
* Wang W,
* Pereira MA.

Department of Pathology, Medical College of Ohio, 3055 Arlington Avenue, Toledo, OH 43614-5806, USA. [e-mail]

Dichloroacetic acid (DCA) and trichloroacetic acid (TCA) are mouse liver carcinogens. DNA hypomethylation is a common molecular event in cancer that is induced by DCA and TCA. Hypomethylation of DNA and the insulin-like growth factor-II (IGF-II) gene was determined in DCA- and TCA-promoted liver tumors. Mouse liver tumors were initiated by N-methyl-N-nitrosourea and promoted by either DCA or TCA. By dot-blot analysis using an antibody for 5-methylcytosine, the DNA in DCA- and TCA-promoted tumors was demonstrated to be hypomethylated. The methylation status of 28 CpG sites in the differentially methylated region-2 (DMR-2) of mouse IGF-II gene was determined. In liver, 79.3 +/- 1.7% of the sites were methylated, while in DCA- and TCA-treated mice, only 46.4 +/- 2.1% and 58.0 +/- 1.7% of them were methylated and 8.7 +/- 2.6% and 10.7 +/- 7.4% were methylated in tumors. The decreased methylation found in liver from mice exposed to DCA or TCA occurred only in the upstream region of DMR-2, while in tumors it occurred throughout the probed region. mRNA expression of the IGF-II gene was increased in DCA- and TCA-promoted liver tumors but not in non-involved liver from DCA- and TCA-exposed mice. The results support the hypothesis that DNA hypomethylation is involved in the mechanism for the tumorigenicity of DCA and TCA.

PMID: 15036762

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10807555&query_hl=1&itool=pubmed_DocSum

1: Environ Health Perspect. 2000 May;108 Suppl 2:241-59.Click here to read Links
Mode of action of liver tumor induction by trichloroethylene and its metabolites, trichloroacetate and dichloroacetate.

* Bull RJ.

Pacific Northwest National Laboratory, U.S. Department of Energy, Richland, WA 99352-0999, USA. [e-mail]

Trichloroethylene (TCE) induces liver cancer in mice but not in rats. Three metabolites of TCE may contribute--chloral hydrate (CH), dichloroacetate (DCA), and trichloroacetate (TCA). CH and TCA appear capable of only inducing liver tumors in mice, but DCA is active in rats as well. The concentrations of TCA in blood required to induce liver cancer approach the mM range. Concentrations of DCA in blood associated with carcinogenesis are in the sub-microM range. The carcinogenic activity of CH is largely dependent on its conversion to TCA and/or DCA. TCA is a peroxisome proliferator in the same dose range that induces liver cancer. Mice with targeted disruptions of the peroxisome proliferator-activated receptor alpha (PPAR-alpha) are insensitive to the liver cancer-inducing properties of other peroxisome proliferators. Human cells do not display the responses associated with PPAR-alpha that are observed in rodents. This may be attributed to lower levels of expressed PPAR-alpha in human liver. DCA treatment produces liver tumors with a different phenotype than TCA. Its tumorigenic effects are closely associated with differential effects on cell replication rates in tumors, normal hepatocytes, and suppression of apoptosis. Growth of DCA-induced tumors has been shown to arrest after cessation of treatment. The DCA and TCA adequately account for the hepatocarcinogenic responses to TCE. Low-level exposure to TCE is not likely to induce liver cancer in humans. Higher exposures to TCE could affect sensitive populations. Sensitivity could be based on different metabolic capacities for TCE or its metabolites or result from certain chronic diseases that have a genetic basis.

PMID: 10807555

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10771136&query_hl=1&itool=pubmed_DocSum

1: Toxicology. 2000 Apr 14;145(2-3):115-25.Click here to read Links
In vivo MRI measurements of tumor growth induced by dichloroacetate: implications for mode of action.

* Miller JH,
* Minard K,
* Wind RA,
* Orner GA,
* Sasser LB,
* Bull RJ.

Pacific Northwest National Laboratory, Molecular Biosciences, PO Box 999-P7-56, Richland, WA 99352, USA.

Dichloroacetate (DCA) is an important by-product of the chlorination of drinking water that produces liver cancer in rodents. Assessment of the risk that results from concentrations that occur in drinking water will be dependent upon the mode of action held responsible for these tumors. A study by Stauber and Bull in mice treated with DCA demonstrated a lesion distribution that was skewed towards many small, altered foci of cells that are assumed to be precursor lesions . The present study was designed to determine the extent to which the tumorigenic effects of DCA could be explained by its effect on tumor growth rates (i.e. tumor promoting activity). In vivo magnetic resonance imaging (MRI) allowed accurate determination of growth rates of individual lesions in mice that had been treated with DCA in drinking water at 2 g/l. Out of thirty treated mice, ten were found to have hepatic tumors detectable by MRI at 48 weeks of treatment. These tumor-bearing animals were assigned to two groups matched on the size of lesions observed by in vivo MR1. Treatment with DCA continued in one group of five mice and was stopped in the other. For both groups, tumor growth rates were determined by measuring changes in size of all lesions greater than 1 mm(3) in volume during a 14-day period. Removal of DCA treatment resulted in growth rates that could not be distinguished from zero across all lesion sizes represented in the sample. These data are in agreement with previous observations of DCAs effects on replication rates within tumors (Stauber and Bull, (1997)). Tumor growth rates observed in animals maintained on treatment decreased with lesion volume in a manner that is consistent with a stochastic Gompertz birth-death process proposed by Tan . Parameters of this model obtained by fitting measured growth rates were used to predict the lesion-size distribution expected after one year of DCA treatment. The shape of the predicted lesion-size distribution was similar to that observed by Stauber and Bull (Stauber and Bull, (1997)) in mice sacrificed after 40 weeks of DCA treatment. We conclude that the effects of DCA on the division and/or death rates of spontaneously initiated cells can account for the predominance of small lesions in DCA-treated animals.

PMID: 10771136

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10632141&query_hl=1&itool=pubmed_DocSum

1: J Toxicol Environ Health A. 1999 Dec 24;58(8):485-507. Links
Hepatocarcinogenicity in the male B6C3F1 mouse following a lifetime exposure to dichloroacetic acid in the drinking water: dose-response determination and modes of action.

* DeAngelo AB,
* George MH,
* House DE.

National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. [e-mail]

Male B6C3F, mice were exposed to dichloroacetic acid (DCA) in the drinking water in order to establish a dose response for the induction of hepatocellular cancer and to examine several modes of action for the carcinogenic process. Groups of animals were exposed to control, 0.05, 0.5, 1, 2, or 3.5 g/L DCA in the drinking water for 90-100 wk. Mean daily doses (MDD) of 8, 84, 168, 315, and 429 mg/kg/d of DCA were calculated. The prevalence (percent of animals) with hepatocellular carcinoma (HC) was significantly increased in the 1-g/L (71%), 2-g/L (95%), and 3.5-g/L (100%) treatment groups when compared to the control (26%). HC multiplicity (tumors/animal) was significantly increased by all DCA treatments-0.05 g/L (0.58), 0.5 g/L (0.68), 1 g/L (1.29), 2 g/L (2.47), and 3.5 g/L (2.90)-compared to the control group (0.28). Based upon HC multiplicity, a no-observed-effect level (NOEL) for hepatocarcinogenicity could not be determined. Hepatic peroxisome proliferation was significantly increased only for 3.5 g/L DCA treatment at 26 wk. and did not correlate with the liver tumor response. The severity of hepatotoxicity increased with DCA concentration. Below 1 g/L, hepatotoxicity was mild and transient as demonstrated by the severity indices and serum lactate dehydrogenase activity. An analysis of generalized hepatocyte proliferation reflected the mild hepatotoxicity and demonstrated no significant treatment effects on the labeling index of hepatocytes outside proliferative lesions. Consequently, the induction of liver cancer by DCA does not appear to be conditional upon peroxisome induction or chemically sustained cell proliferation. Hepatotoxicity, especially at the higher doses, may exert an important influence on the carcinogenic process.

PMID: 10632141

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9703483&query_hl=1&itool=pubmed_DocSum

1: Environ Health Perspect. 1998 Aug;106 Suppl 4:989-94.Click here to read Links
Clinical pharmacology and toxicology of dichloroacetate.

* Stacpoole PW,
* Henderson GN,
* Yan Z,
* James MO.

Department of Medicine, College of Medicine, University of Florida, Gainesville, USA. [e-mail]

Dichloroacetate (DCA) is a xenobiotic of interest to both environmental toxicologists and clinicians. The chemical is a product of water chlorination and of the metabolism of various drugs and industrial chemicals. Its accumulation in groundwater and at certain Superfund sites is considered a potential health hazard. However, concern about DCA toxicity is predicated mainly on data obtained in inbred rodent strains administered DCA at doses thousands of times higher than those to which humans are usually exposed. In these animals, chronic administration of DCA induces hepatotoxicity and neoplasia. Ironically, the DCA doses used in animal toxicology experiments are very similar to those used clinically for the chronic or acute treatment of several acquired or hereditary metabolic or cardiovascular diseases. As a medicinal, DCA is generally well tolerated and stimulates the activity of the mitochondrial pyruvate dehydrogenase enzyme complex, resulting in increased oxidation of glucose and lactate and an amelioration of lactic acidosis. By this mechanism, the drug may also enhance cellular energy metabolism. DCA is dehalogenated in vivo to monochloroacetate and glyoxylate, from which it can be further catabolized to glycolate, glycine, oxalate, and carbon dioxide. It remains to be determined whether important differences in its metabolism and toxicology exist in humans between environmentally and clinically relevant doses.

PMID: 9703483

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=8980710&query_hl=1&itool=pubmed_DocSum

1: Toxicology. 1996 Dec 18;114(3):207-21.Click here to read Links
The carcinogenicity of dichloroacetic acid in the male Fischer 344 rat.

* DeAngelo AB,
* Daniel FB,
* Most BM,
* Olson GR.

National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.

The chlorinated acetic acids, in particular dichloroacetic acid (DCA), are found as chlorine disinfection by-products in finished drinking water supplies. DCA has previously been demonstrated to be a mouse liver carcinogen. Chronic studies are described in which male Fischer (F344) rats were exposed to DCA in their drinking water. In the first study, 28 day old rats were exposed to a regimen of 0.05, 0.5 and 5.0 g/l DCA. When animals in the high dose group began to exhibit peripheral hind leg neuropathy, the dose was lowered in stages to 1 g/l. These animals were sacrificed at 60 weeks due to the severe, irreversible neuropathy and were not included in this analysis. The remaining groups of animals were treated for 100 weeks. In the second study, rats were initially exposed to 2.5 g/l DCA which was lowered to 1 g/l after 18 weeks. The mean daily concentration (MDC) of 1.6 g/l was calculated over the 103 week exposure period. Time-weighted mean daily doses (MDD) based on measured water consumption were 3.6, 40.2 and 139 mg/kg bw/day for the 0.05, 0.5 and 1.6 g/l DCA respectively. Based upon the pathologic examination, DCA induced observable signs of toxicity in the nervous system, liver and myocardium. However, treatment related neoplastic lesions were observed only in the liver. A statistically significant increase of carcinogenicity (hepatocellular carcinoma) was noted at 1.6 g/l DCA. Exposure to 0.5 g/l DCA increased-hepatocellular neoplasia, (carcinoma and adenoma) at 100 weeks. These data demonstrate that DCA is an hepatocarcinogen to the male F344 rat. Calculation of the MDD at which 50% of the animals exhibited liver neoplasia indicated that the F344 male rat (approximately 10 mg/kg bw/day) is ten times more sensitive than the B6C3F1 male mouse (approximately 100 mg/kg bw/day). A "no observed effects level' (NOEL) of 0.05 g/l (3.6 mg/kg/day) was the same as for the mouse (3-8 mg/kg/day).

PMID: 8980710

[MonkeyFunk]

23. oh ffs...

it's not a cure for cancer. It's a compound that shows some degree of promise.

I can kill cancer cells by soaking them in bleach, but Clorox is not yet a cure for cancer.