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Oxaloacetate


dumbcritic
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It has been shown to reduce blood and brain glutamate levels as well as glycolysis. A trial in patients with ndGBM should be open in Dec https://clinicaltrials.gov/ct2/show/NCT04450160


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Daniel
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Posted by: @dumbcritic

It has been shown to reduce blood and brain glutamate levels as well as glycolysis. A trial in patients with ndGBM should be open in Dec https://clinicaltrials.gov/ct2/show/NCT04450160

Thank you!

Just to add a few more references:

Oxaloacetate induces apoptosis in HepG2 cells via inhibition of glycolysis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911603/

Nontoxic Targeting of Energy Metabolism in Preclinical VM-M3 Experimental Glioblastoma https://www.frontiersin.org/articles/10.3389/fnut.2018.00091/full

 


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Jcancom
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@dumbcritic, thank you for your recent series of postings. We have continued to make progress in our understanding of metabolic biology. Adding in oxacolactate is another control lever. It is quite impressive to see how the net around cancer is closing.

Cancer has a number of circuits that it can take advantage of. For example, MCT-1 open cancer cells offers these cells a range of advantages. Yet, these cells would then be open to the effects of 3-BP. Products are in development that would also close down MCT-1.

NAD+/NADH is another point of control. syromet can stop the recycling of NADH--> NAD+. Now oxacolactate can also change the ratio. There are several others that we have explored.

Each of these control points can give us the opportunity to control cancer cell biology. We have been accumulating a list of treatments that will attack cancer if an activity is high or low. The escape routes for  cancer to escape appear to be dwindling. 

As we have seen so many of the glycolytic/TCA intermediates have anti-cancer effects. Citrate, oxacolactate, pyruvate ... . Cancer to a substantial extent depends on a simple supply of glucose that it can convert to lactate resulting in a simple net 0 production of NAD+/NADH. Almost any other of these glycolytic chemicals will throw off the ratio and the simple logic.  

Oncolytic viruses have also captured my attention. It would not be entirely unexpected that they could wind up being the path to the cure through regulators. A treatment that only affects cancer cells is a winner right from the start. Of course, monotherapy is only the first step in the development of a treatment; here is research that was able to amplify the effects of oncolytic viruses  https://pubmed.ncbi.nlm.nih.gov/29367345/


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dumbcritic
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@daniel Thanks. I know a few companies on Amazon (the U.S. site) claim to sell it, but I don't know if they are trustworthy, and even if so it could be cost prohibitive (depending on the dose(s) recommend).


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dumbcritic
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@jcancom No problem. Speaking of OVs, Replimmune's lead product (RP1) is currently in three registration-directed clinical trials and if all goes to plan it should be approved in the next few years [1]. However, 2-DG has been shown to attenuate replication [2], but could synergise with the NDV [3]. I think some clinics in Germany offers the latter. Co-administration (via IT injections) with GM-CSF and/or hyaluronidase may be of help as well.

 

Refs:

1 Dr. Coffin invented all three and was behind the only FDA and EMA approved OV to date (Imlygic) https://jitc.biomedcentral.com/articles/10.1186/s40425-019-0682-1
2 https://pubmed.ncbi.nlm.nih.gov/4350224/
3 https://www.frontiersin.org/articles/10.3389/fmolb.2019.00090/full


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Jcancom
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@dumbcritic, thank you again for your highly informative posts. It is very encouraging that German clinics are possibly offering oncolytic treatment as you suggested. This is should be a safe treatment that could be amplified by various other approaches. I would think that a generic oncolytic treatment should become the standard in cancer management over the medium term.I would also be very encouraged if tehy were treating with anaerobic bacteria as well.

critic, I am quite interested in your opinion of lactate monitors. This has been discussed over a number of years on the compass and on this forum. Monitoring metabolic biomarkers such as lactate, ketones and glucose would seem to be a highly relevant approach in cancer. They probably should be measures that people measure 24/7. Such monitors for glucose and lactate are on or will soon be on the market. Being able to see how treatments could manipulate these values would seem to me to be invaluable. Consider if you treated with DCA. It could be highly informative if there a lactate drop. You could have some insight into whether DCA were doing what you expected it to. If we gained experience with this then perhaps we could see a pattern of responses that occurred with specific lactate changes. People might be able to rapidly cycle through metabolic treatments that did not appear to be responding by consulting the biomarker evidence. As it is now, posters are trying treatments though they sometimes will continue treatment for months without a clear sense of efficacy. Yet, this is one of the main advantages of metabolic treatment, responses (especially as measured by biomarkers can occur rapidly). The 3-BP melanoma patient had a very large response within a day (probably an hour or two) or treatment.

I would be very interested to hear your comments about the feasibility of this idea.

 


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