Cheap, safe cure for most cancers?

Dichloroacetate

· Use: Lactate lowering
· Dose: 25 mg/kg/day by mouth
· Clinical
o Onset: 3 to 12 months after starting medication
o Frequency: 86%
o Paresthesias: Distal limb
o Pain
o Numbness: Distal
o Gait disturbances & falling
o Course: Partial or complete improvement aver 6 to 18 months after stopping drug
· Laboratory: Axonal neuropathy
o NCV: Reduced CMAP & SNAP amplitudes
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http://www.neuro.wustl.edu/neuromuscular/nother/toxic.htm#dichloroacetate



The same author (Stacpoole):

in: Metabolism. 1989 Nov;38(11):1124-44. Links

The pharmacology of dichloroacetate.
·
Stacpoole PW.
Department of Medicine, University of Florida, College of Medicine, Gainesville 32610.

Dichloroacetate (DCA) exerts multiple effects on pathways of intermediary metabolism. It stimulates peripheral glucose utilization and inhibits gluconeogeneis, thereby reducing hyperglycemia in animals and humans with diabetes mellitus. It inhibits lipogenesis and cholesterolgenesis, thereby decreasing circulating lipid and lipoprotein levels in short-term studies in patients with acquired or hereditary disorders of lipoprotein metabolism. By stimulating the activity of pyruvate dehydrogenase, DCA facilitates oxidation of lactate and decreases morbidity in acquired and congenital forms of lactic acidosis. The drug improves cardiac output and left ventricular mechanical efficiency under conditions of myocardial ischemia or failure, probably by facilitating myocardial metabolism of carbohydrate and lactate as opposed to fat. DCA may also enhance regional lactate removal and restoration of brain function in experimental states of cerebral ischemia. DCA appears to inhibit its own metabolism, which may influence the duration of its pharmacologic actions and lead to toxicity. DCA can cause a reversible peripheral neuropathy that may be related to thiamine deficiency and may be ameliorated or prevented with thiamine supplementation. Other toxic effects of DCA may be species-specific and reflect marked interspecies variation in pharmacokinetics. Despite its potential toxicity and limited clinical experience, DCA and its derivatives may prove to be useful in probing regulatory aspects of intermediary metabolism and in the acute or chronic treatment of several metabolic disorders.
PMID: 2554095 [PubMed - indexed for MEDLINE]
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Same author who co-authored the paper cited discussing dichloroacetate as an environmental hazard (Jia M, Coats B, Chadha M, Frentzen B, Perez-Rodriguez J, Chadik PA, Yost RA, Henderson GN, Stacpoole PW :
Human kinetics of orally and intravenously administered low-dose 1,2-(13)C-dichloroacetate. in: J Clin Pharmacol. 2006 Dec;46(12):1449-59.)

wrote the above paper in 1989. He also authored or co-authored additional papers on dichloroacetate found here:

http://www.ncbi.nlm.nih.gov/entrez/...bmed_AbstractPlus&term="Stacpoole+PW"[Author]

I am fairly certain there is only “one” dichloroacetate in PW Stacpoole’s area of study so he can be e-mailed to settle the matter if necessary explaining that there are forum members who think his paper mentioning dichloroacetate in the environment* is not the same dichloroacetate that has recently been suggested for cancer treatment and which has been used for MELAS and related cardiac and metabolic conditions. I think the Belgian paper erroneously refers to dichloroethane as DCA which is a separate issue. I cannot fathom why the Florida paper on the kinetics of dichloroacetate would be any other substance other than the dichloroacetate being discussed here.

(*"Dichloroacetate (DCA) is a putative environmental hazard, owing to its ubiquitous presence in the biosphere and its association with animal and human toxicity." from the opening line of the abstract)

The Belgian confusion could even be due to the way A and E are pronounced in French or Flemish if this paper was orally dictated and then the translator failed to take this into account when translating into English. I am certain neither letter are pronounced as letters the same way they are pronounced in English.

JJM: The J Clin Pharm paper, cited by SG, that concerns a pollutant is pretty clearly not relevant to the discussion of the drug. I, too, appreciate the other articles cited by SG, and the explanation of the Warburg effect by Schneib.
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I agree that dichloroacetate as a pollutant may not be directly relevant to its use as a drug but I do not agree it isn't the same molecule. I cited above the entry for dichloroacetate in the Sigma-Aldrich database which indicates the availability of several different salts (Na, K) and configurations of this substance, 11 in all. I wouldn't go so far as to state it is pretty "clearly" not relevant. If it is common in the environment and could cause neuropathy in, say animals and humans that chronically come in contact (e.g. ingest) with it then there is relevance in its use as a deliberately ingested drug. The kinetics of how human metabolism handles the drug becomes relevant since from what is known about the deleterious effects of the substance indicate it occurs over time and on reaching specific dosages. This would be of relevance both to it being ingested from the environment or deliberately administered.




The following structural diagram is from the only dichloroacetate entry in the following database:

http://www.neuro.wustl.edu/neuromuscular/nother/toxic.htm#dichloroacetate
 

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SteveGrenard said:
I am fairly certain there is only “one” dichloroacetate in PW Stacpoole’s area of study so he can be e-mailed to settle the matter if necessary explaining that there are forum members who think his paper mentioning dichloroacetate in the environment* is not the same dichloroacetate that has recently been suggested for cancer treatment and which has been used for MELAS and related cardiac and metabolic conditions. I think the Belgian paper erroneously refers to dichloroethane as DCA which is a separate issue. I cannot fathom why the Florida paper on the kinetics of dichloroacetate would be any other substance other than the dichloroacetate being discussed here.
Click to expand...
There is only one structure for dichloroacetate. An acetate anion consists of a methyl group (a carbon atom with three hydrogen atoms attached to it) attached to a second carbon which has two oxygen atoms attached to it and a negative charge (for the acetic acid molecule, the carboxyl group is usually portrayed as a carbon atom with one oxygen attached via a double bond and an -OH group attached via a single bond).

In dichloroacetate the two chlorine atoms replace two of the hydrogens in the methyl group. As this group is free to revolve with respect to the carboxyl group there is only one possible structure.
 
JJM said:
[Bold added] What the US calls DCA is still not 1,2-dichloroacetate; as I wrote previously, that is a misnomer for CH2ClCOCl. In acetate (CH3CO2-) the methyl group (CH3) is numbered 2, and anything substituted there is numbered 2. The putative drug is 2,2-dichloroacetate, or CHCl2CO2-. If the chlorine were on the #1 carbon, it would not be called acetate, it would be an acetyl chloride. In fact, unless editorial policies have recently changed, I can't imagine a chemist referring to 2,2-dichloroacetate; it would simply be "dichloroacetate" since there is nowhere else to put chlorine on acetate.

The J Clin Pharm paper, cited by SG, that concerns a pollutant is pretty clearly not relevant to the discussion of the drug. I, too, appreciate the other articles cited by SG, and the explanation of the Warburg effect by Schneib.
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Could the term "1,2-(13)C-dichloroacetate" used in the paper cited by Steve relate to labeling with carbon-13 so that the dichloroacetate administered and its metabolites could be identified, with the "13" indicating that they used the carbon-13 isotope to label the dichloroactate, and the "1,2" indicating that both carbon atoms in the acetate group were carbon-13, rather than saying anything about the structure? If not, what does the "13" refer to?

Or perhaps the reDiscovery Institute have succeeded in one of their aims.
 
yup.

Methyl dichloroacetate-1-13C (1)


Linear Formula: Cl2C13COOCH3, Formula Weight: 142.95
604291 99 atom % 13C (Aldrich)
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From the Sigma-Aldrich Advanced Search Function. The 13 is written as a superscript.

Go to:

http://www.sigmaaldrich.com/catalog/search/AdvancedSearchPage


enter: dichloroacetate

in product name (first) box and search. When you get back the list of dichloroacetate molecules, click on the Methyl dichloroacetate with C13 to see the formula.


604291

Aldrich Methyl dichloroacetate-1-13C

99 atom % 13C

Molecular Formula: Cl2C13COOCH3

Molecular Weight142.95
 
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Mojo said:
Could the term "1,2-(13)C-dichloroacetate" used in the paper cited by Steve relate to labeling with carbon-13 so that the dichloroacetate administered and its metabolites could be identified, with the "13" indicating that they used the carbon-13 isotope to label the dichloroactate, and the "1,2" indicating that both carbon atoms in the acetate group were carbon-13 ...
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You are right about that. However, any reference to 1,2-dichloroacetate, not isotopically-labelled, is a mistake.

[snip, edited to correct:] I re-examined the J Clin Pharm paper, and I think it is referring to acetate. Sorry for my mistake.

Thanks for that clarification.
 
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SteveGrenard said:
Aldrich Methyl dichloroacetate-1-13C

99 atom % 13C

Molecular Formula: Cl2C13COOCH3
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In this case, the 13C label is exclusively in carbon #1, not both carbons as discussed above. (It is interesting to note a slight error in the molecular formula published by Aldrich).
 
JJM said:
The putative antitumor compound, dichloroacetate, has the formula CHCeither the anion or an ester; in this case it is pretty clearly the anion) which is 2,2-dichloroacetate, not 1,2. .
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The 1,2 is referring to the positions of the carbon 13 atoms.
 
That's the sort of thing I was expecting to hear. Many drugs do fine on a sample in a dish, but when you try to use them on a living human being, things don't work out as expected. Hopefully, it will be at least one more useful weapon in the surgeons armoury when he is treating the disease.
 
"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.
Until now it had been assumed that cancer cells used glycolysis because their mitochondria were irreparably damaged. However, Michelakis’s experiments prove this is not the case, because DCA reawakened the mitochondria in cancer cells. The cells then withered and died (Cancer Cell, DOI: 10.1016/j.ccr.2006.10.020)."

So are they saying that cancer cells operate anaerobically? I mean, that is what happens when you stop at glycolysis and don’t complete Kreb’s (a chemical cycle in the mitochondrion). And I wonder what about turning on the mitochondrion (and thus allowing the cell to produce vast amounts of additional energy aerobically) would cause them to die. I am skeptical...
 
Yes.


Payne AG.
Steenblock Research Institute, 1064 Calle Negocio #B, San Clemente, CA 92673, United States.
Chemo- and radio-resistant cancer cells within solid tumors undermine the effectiveness of these approaches to achieving oncolysis. These resistant cells and clusters of cells typically thrive at low oxygen tensions and are reliant on anaerobic metabolic pathways that churn out lactate. This hypoxic state is one that can be exploited and in this paper a novel method is advanced involving tumor cell infiltration by bifidobacterium species which should bring about prodigious lactate synthesis; concomitant blocking of its enzymatic degradation by urea as well as export (from the cell) by use of quercetin; depletion of ATP using exogenous thyroid; and compromised oxidative catabolism of free fatty acids and amino acids via oral intake of l-hydroxycitrate, melatonin and nontoxic NDGA. This "anaerobic pathway cocktail", it is hypothesized, will bring about a profound reduction in intracellular pH and a compromised state of cellular energetics sufficient to effect oncolysis.
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Energy metabolism of the cancer cell: example of mitochondria-rich endocrine tumors]
[Article in French]
· Malthiery Y,
· Savagner F.
Inserm U 694, Biochimie et Biologie moleculaire, CHU, 4, rue Larrey, 49033 Angers Cedex. Yvmalthiery@chu-angers.fr


Most solid tumours preferentially develop glycolytic metabolism, often accompanying tumor aggressiveness. Increase in nucleic acid synthesis is associated with cell proliferation and glucose shunting to the pentose phosphate pathway. High glucose consumption is more associated with a metabolic adaptation than with a mitochondrial defect. Tumor cells do not present specific genetic modifications but adapt their metabolic capacities to their priority needs. However their metabolisms depend on oncogene expression more specifically expressed in this context. The glycolytic pathway is favored by tumor proliferation under hypoxia. Stabilization of HIF1 factor may explain the glycolytic metabolism of the tumors in an anaerobic environment. We demonstrate in two types of mitochondrial rich tumors, that specific defects induce completely different metabolic directions: when familial paragangliomas present a glycolytic metabolism, thyroid oncocytic tumors develop a specific oxidative metabolism.
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Trying2Bopen said:
"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.
Until now it had been assumed that cancer cells used glycolysis because their mitochondria were irreparably damaged. However, Michelakis’s experiments prove this is not the case, because DCA reawakened the mitochondria in cancer cells. The cells then withered and died (Cancer Cell, DOI: 10.1016/j.ccr.2006.10.020)."

So are they saying that cancer cells operate anaerobically? I mean, that is what happens when you stop at glycolysis and don’t complete Kreb’s (a chemical cycle in the mitochondrion). And I wonder what about turning on the mitochondrion (and thus allowing the cell to produce vast amounts of additional energy aerobically) would cause them to die. I am skeptical...
Click to expand...

It is the mitochondria that are responsible for apoptosis- the death of old/diseased cells. No mitos, nothing to kill the bad cells. Good mitos, cancers die before the tumor gets big enough to find.

Hmmm, does that mean that folks with mitochondrial diseases have more cancers? I hadn't heard... though I do have a mito disease, and lately an adrenal 'incidental-oma'... Well, I guess they will have cured my heart disease, when the cancer kills me first...
 
I saw a student article about how the Media (as well as any private funding sources) have ignored this possible cheap, safe, cancer treatment. Being a skeptic, I checked it out. Because you might think a possible cure for ANY cancer would be big news. And a safe, known substance, that is dirt cheap and can be tested in Phase II right away, would be really big news. That the Media would just ignore this, doesn't make sense. Conspiracy theory and all that.

So Google me some News.
Results 1 - 10 of about 59 for Dichloroacetate.

Hmmm, very few stories, hardly any MegaMedia names at all there. A lot of woo sounding stuff about how it won't get funding, how this discovery is being ignored by the press, how it will never be tested.

Maybe Google isn't working. Lets search for acetate.
416 for acetate.

OK, Google is working. (damn, a lot of stories about acetate, breaking news there)

So being a skeptic, check some News sites.

FOX
http://search2.foxnews.com/search?i...*&filter=0&sort=date:D:S:d1&q=Dichloroacetate
0 results

ABC
http://abcnews.go.com/search?searchtext= Dichloroacetate&type=feature
0 hits

NBC
http://nbc.resultspage.com/search?ts=custom&p=Q&uid=400427844&w=Dichloroacetate
0 hits

BBC
http://search.bbc.co.uk/cgi-bin/sea...tate&btn=Search&uri=/?ok&scope=all&go=toolbar
Sorry

There are no results for "Dichloroacetate" on the BBC website.

WTF? Did I spell this wrong?
http://en.wikipedia.org/wiki/Dichloroacetate

No, that is correct. OK something is fookin nuts here.

http://www.msnbc.msn.com/?search=MS...bmit=Search&id=11881780&FORM=AE&os=0&gs=1&p=1
3 hits


Aha! See? The media isn't ignoring the story! No wait, those are all stories about the original story. Jan 22, 23 2007

Hmmm... OK skeptics, debunkin time.

Google News search for "Cancer" stories, 66,838 for cancer.

Google News for cancer+dichloroacetate
about 58 for cancer dichloroacetate.

WTF???

:hb:

Looks like the media is ignoring the story. How strange.
 
Google News, cancer+cure

3,023 for cancer cure.

But no stories about this??? I looked through the first 60, stem cells, Herpes as Brain Cancer Treatment, annual Swing Fore a Cure Golf Classic at Hawk Ridge Country Club, yadda yadda yadda, nothing on Dichloroacetate.

Hmm...

Seems that two side effects of Dichloroacetate are anxiolytic and sedative effects. In other words, it reduces anxiety, and makes you sleepy.

I can see it already, woos facing chemo are going to try this instead. People may die, people may live. The Government will have to shut down illegal Dichloroacetate clinics, Mexico will open woo treatment Spas based on this. People will claim it healed them of cancer, it will be banned from research. Then the Media will cover it.

:wackylaugh:
 
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