3 replies to this topic

[pone11]

There is a great thread going on the use of 3-bromopyruvate (3-BP) - an alkalyzing agent - to fight cancer.   3-BP is a pyruvate mimic that exploits the large numbers of glucose shuttles on the surface of a cancer cell to get into cancer cells in large quantities and kill the cancer by shutting down glycolysis:

 

http://www.longecity...-a-cancer-cure/

 

I had the idea in that thread that we could use 3-BP to locate early stage cancers.   The idea is that during your yearly checkup, they would give you a controlled infusion of 3-BP, then monitor you in the following days for tumor lysis products.   If you had a small growing cancer, or tissues that were pre-cancerous, you would expect to find tumor lysis products.   Here is original post:

 

http://www.longecity...e-2#entry711578

 

Early detection of the cancer - particularly if it was pre-cancerous - would greatly enhance your treatment options and survival rates.   Particularly for the impossible-to-treat cancers like some kinds of pancreatic cancers, we might discover that 3-BP could completely eradicate the cancer during very early intervention.   These kinds of cancers rarely show symptoms until it is much too late.

 

User @resveratrol_guy asked me to document this idea in a separate thread, so this thread is my attempt at that.

 

 

 

Edited by pone11, 15 February 2015 - 01:08 AM.

[resveratrol_guy]

I support this brilliant idea.

 

Now... how much 3BP to administer? Given that "normal" cells are 95% OXPHOS and 5% glycolytic (percentage of mitochondria in one state or the other), and glycopathological cells are 50% OXPHOS and 50% glycolytic, crudely speaking, I would suggest setting the "Warburg threshold" to around 23% glycolytic, which is the average. That is, administer enough 3BP to deal a fatal blow to 23% glycolytic cells, but not 24% ones (or thereabouts). This would be high enough to protect truly normal cells, but low enough to capture many precancerous cells.

 

A more sophisticated embodiment would involve a continuous Warburg threshold, gradually lowering the dose from, say, 51% to 8%, while monitoring the hematological proteome for tumor lysis in real time. Once lysis was detected, the process would stop. The output would be the Warburg threshold at which a certain characteristic degree of lysis occurred. For example, if 48% turned out to create a lysis spike, then we would suspect a nearly metastatic cancer; if 10% did the job, then we would have an early stage one which might perhaps be benign.

 

For a crude mockup, we could just take textbook blood tests before and after each stepdown in the Warburg threshold and watch for vague signs of lysis, e.g. elevated ESR or BUN or whatever it happens to be. Using several weak signals is as good as using one strong one, qualitatively speaking.

 

It's cheap, at least in its first incarnation, and is broad-based yet emphasizes the detection of malignant tumors, thereby bypassing the traditional complaint that sophisticated imaging and blood tests encourage unncessary surgeries and waste medical resources. This sounds like a Kickstarter campaign, at some point...

 

[pone11]

I support this brilliant idea.

 

Now... how much 3BP to administer? Given that "normal" cells are 95% OXPHOS and 5% glycolytic (percentage of mitochondria in one state or the other), and glycopathological cells are 50% OXPHOS and 50% glycolytic, crudely speaking, I would suggest setting the "Warburg threshold" to around 23% glycolytic, which is the average. That is, administer enough 3BP to deal a fatal blow to 23% glycolytic cells, but not 24% ones (or thereabouts). This would be high enough to protect truly normal cells, but low enough to capture many precancerous cells.

 

A more sophisticated embodiment would involve a continuous Warburg threshold, gradually lowering the dose from, say, 51% to 8%, while monitoring the hematological proteome for tumor lysis in real time. Once lysis was detected, the process would stop. The output would be the Warburg threshold at which a certain characteristic degree of lysis occurred. For example, if 48% turned out to create a lysis spike, then we would suspect a nearly metastatic cancer; if 10% did the job, then we would have an early stage one which might perhaps be benign.

 

For a crude mockup, we could just take textbook blood tests before and after each stepdown in the Warburg threshold and watch for vague signs of lysis, e.g. elevated ESR or BUN or whatever it happens to be. Using several weak signals is as good as using one strong one, qualitatively speaking.

 

It's cheap, at least in its first incarnation, and is broad-based yet emphasizes the detection of malignant tumors, thereby bypassing the traditional complaint that sophisticated imaging and blood tests encourage unncessary surgeries and waste medical resources. This sounds like a Kickstarter campaign, at some point...

 

I think FDA might shut down a kickstarter project.  I handed this idea off to a researcher, and he liked it but said it would never get by a review board.   The fear would be that - even at a low dose - one in N people might get really sick or die.   You need the benefit of a large population study to establish safety at different doses within your proposed protocol.

 

I do wish I was a billionaire because this seems like the kind of project that can make a huge difference to the world and the research would not be rocket science, in either complexity or in cost.

[resveratrol_guy]

 

I support this brilliant idea.

 

Now... how much 3BP to administer? Given that "normal" cells are 95% OXPHOS and 5% glycolytic (percentage of mitochondria in one state or the other), and glycopathological cells are 50% OXPHOS and 50% glycolytic, crudely speaking, I would suggest setting the "Warburg threshold" to around 23% glycolytic, which is the average. That is, administer enough 3BP to deal a fatal blow to 23% glycolytic cells, but not 24% ones (or thereabouts). This would be high enough to protect truly normal cells, but low enough to capture many precancerous cells.

 

A more sophisticated embodiment would involve a continuous Warburg threshold, gradually lowering the dose from, say, 51% to 8%, while monitoring the hematological proteome for tumor lysis in real time. Once lysis was detected, the process would stop. The output would be the Warburg threshold at which a certain characteristic degree of lysis occurred. For example, if 48% turned out to create a lysis spike, then we would suspect a nearly metastatic cancer; if 10% did the job, then we would have an early stage one which might perhaps be benign.

 

For a crude mockup, we could just take textbook blood tests before and after each stepdown in the Warburg threshold and watch for vague signs of lysis, e.g. elevated ESR or BUN or whatever it happens to be. Using several weak signals is as good as using one strong one, qualitatively speaking.

 

It's cheap, at least in its first incarnation, and is broad-based yet emphasizes the detection of malignant tumors, thereby bypassing the traditional complaint that sophisticated imaging and blood tests encourage unncessary surgeries and waste medical resources. This sounds like a Kickstarter campaign, at some point...

 

I think FDA might shut down a kickstarter project.  I handed this idea off to a researcher, and he liked it but said it would never get by a review board.   The fear would be that - even at a low dose - one in N people might get really sick or die.   You need the benefit of a large population study to establish safety at different doses within your proposed protocol.

 

I do wish I was a billionaire because this seems like the kind of project that can make a huge difference to the world and the research would not be rocket science, in either complexity or in cost.

 

 

Fair enough. Where's Peter Nygaard?

 

Seriously, all that's required is (1) patients who understand the risks but are desperate to know their cancer status and willing to contribute to a humanitarian effort and (2) a pro-stem-cell government (nod to Bahamas, Thailand, and others). As more and more properly informed patients are recruited, the risk profile will become increasingly clear. I'm sure that if you said "I have a new scanner that can see inside you by blasting you with xrays, but don't worry it's not too much", you also might have trouble raising money or getting approval. But, CT scanners exist. So why not a lysis scanner?