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#31 pone11
Posted 01 February 2015 - 03:47 PM resveratrol_guy, on 01 Feb 2015 - 4:08 PM, said: So as I understand it, plain vanilla IV 3BP is basically useless; one needs paracetamol to lower the glutathione antioxidant defense of the tumor cells in order to make it effective. (Organ-targetted 3BP-only therapy is potententially effective, but the delivery mechanics are obviously nontrivial, so IMO this is an impractical approach.) So it kind of sounds like 3BP causes HK2 to indirectly downregulate glycolysis. Then, robbed of half their energy, normal oxidative stress becomes an overwhelming tax on the cancer cells which are also glutathione depleted, resulting in cell death. (Not to forget salinomycin, but I'm no expert on it.) Somehow, during this process, we need to preferentially protect healthy cells. Perhaps a proapoptic agent which is also an antioxidant, such as reveratrol or pterostilbene, would be useful. c60oo (and similarly, nicotinamide riboside) might be useful as well, judging from the original Baati experiment, although it's not completely clear whether or not it would protect cancer once it had already developed, even though it appears to prevent it in the first place. Anyway, I'm just trying to think of a way to protect the patient from undue oxidative and neurological stress (nicotine? lithium? NGF eye drops?) while we fry the cancer. This isn't idle fascination; a friend of a friend of mine (not the guy above) has metastatic pancreatic cancer. I've told his wife about 3BP, for starters.
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A ketogenic diet has obvious benefits, but is unpalatable to some people, even some people with cancer. (And with digestive cancers, the fat load would require increased synthetic enzyme intake, if it could be tolerated at all.)

[Mods: IMO this is "the" 3BP thread, based on internal search ranking, so I vote to keep it that way.] The way I read the original research that I responded to, cancer upregulates the HK2 enzyme, and it uses this to increase glucose going into the damaged mitochondria that are stuck in glycolysis. The primary mechanism that explains the success of 3BP is that it downregulates HK2 in all cells. But because cancer cells are the only ones that rely on HK2 heavily for glycolysis, this ends up being a method of attack that is preferential against cancer. Downregulating HK2 in a normal cell will not kill it.

It was not clear to me that you had to have paracetamol for the effect to take place. Did you find any in vitro studies where 3BP alone did not work, but 3BP + paracetamol did?

Ketogenic diet should be an additive therapy here, as would be any other pro-oxidative therapy. Dominic D'Agostino's research shows the added benefits of hyperbaric oxygen. As a pure speculation, I am guessing that ozone injection (as practiced by Dr Shallenberger in Nevada) might have a positive effect as well, since it tends to flood the cell with oxygen and create a cascade of events that increase the NAD+/NADH ratio and speeds up aerobic metabolism.

One of the most intriguing parts of Dominic's research is his finding that a ketone ester will put a mouse into a chemically induced ketosis for hours. The esters are too expensive at this point to make commercially, but it suggests that at some point in the future it might be possible to buy an ester and spend much of the day in ketosis without the pain of a ketogenic diet.
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#32 pone11
Posted 01 February 2015 - 03:51 PM mag1, on 01 Feb 2015 - 4:18 PM, said: Thanks. I am liking this is THE 3-BP thread.
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I want to generate a positive vibe so that all the cool people will join in. The problem with this forum is that there is no good way to filter down all the bogus cancer threads so that ones like 3-BP are more prominent.

Longecity does not have many hard core cancer patients posting, so the threads do not have the same urgency as elsewhere. Check out some of the latest posts from the cancercompass forum. http://www.cancercom...all,65701,0.htm The best way to get attention on Longecity is to generate traffic in the thread. You might want to cross post significant new posts in that other thread.

You don't want urgency. You want respect for good science and the truth. Forums with desperate patients tend to just give a thumbs up for every idea including bad ones.

Have you found any new human trials of 3BP conducted within peer review research of an academic institution, not by a for-profit cancer clinic?

Edited by pone11, 01 February 2015 - 03:52 PM.


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#33 resveratrol_guy
Posted 01 February 2015 - 04:57 PM pone11, on 01 Feb 2015 - 4:47 PM, said:
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The way I read the original research that I responded to, cancer upregulates the HK2 enzyme, and it uses this to increase glucose going into the damaged mitochondria that are stuck in glycolysis. The primary mechanism that explains the success of 3BP is that it downregulates HK2 in all cells. But because cancer cells are the only ones that rely on HK2 heavily for glycolysis, this ends up being a method of attack that is preferential against cancer. Downregulating HK2 in a normal cell will not kill it.

It was not clear to me that you had to have paracetamol for the effect to take place. Did you find any in vitro studies where 3BP alone did not work, but 3BP + paracetamol did?

Ketogenic diet should be an additive therapy here, as would be any other pro-oxidative therapy. Dominic D'Agostino's research shows the added benefits of hyperbaric oxygen. As a pure speculation, I am guessing that ozone injection (as practiced by Dr Shallenberger in Nevada) might have a positive effect as well, since it tends to flood the cell with oxygen and create a cascade of events that increase the NAD+/NADH ratio and speeds up aerobic metabolism.

One of the most intriguing parts of Dominic's research is his finding that a ketone ester will put a mouse into a chemically induced ketosis for hours. The esters are too expensive at this point to make commercially, but it suggests that at some point in the future it might be possible to buy an ester and spend much of the day in ketosis without the pain of a ketogenic diet.

Maybe it's an overstatement to say that paracetamol is necessary to potentiate the benefits of IV 3BP. But then again, is there any good reason not to use it, because it's a well-understood and low-risk drug if we're talking about short term moderate doses? Temporary glutathione suppression should not be an issue, if only we can preferentially protect the normal cells.

I do recall D'Agostino mentioning that hyperbaric oxygen is anticancer (most likely due to favoring OXPHOS over glycolysis), but in the same video, he showed images of cell membrane damage resulting from the therapy. Damaged membranes might increase the risk of cancer in the long term. So I would think the ketogenic approach (especially the "ketodrinks" that you mentioned) would be safer. (Hopefully a less regulated marketplace will spur mass-production soon, so the product will be cheap the second that the research is done.)

However, despite the apparent promise of 3BP and antiglycolysis in general, I think the opposite approach is worth considering: demotivate the cancer by putting it on welfare, wherein it becomes addicted to chemotherapy to the detriment of its aggressive capacity.


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#34 mag1
Posted 01 February 2015 - 06:32 PM The article with the patient with metastatic melanoma showed a fairly modest response when given 8 doses of 3-BP at the recommended dose. However, two combination doses of 3-BP and paracetamol cured the cancer! (see figure 3 from the below url).
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http://www.ncbi.nlm....les/PMC4110469/

The other published human 3-BP patient report noted a very large anti-tumor response to straight 3-BP though at a higher dose than in the above report.

http://www.ncbi.nlm....pubmed/22382780

It should be pointed out that paracetamol is nothing more than acetaminophen. We had a bottle of it lying around and did not even know that this was paracetamol. Is a prescription even required for it?

The readers of this thread are a hard bunch to impress. The cancer compass url that I gave in a earlier post, mentioned that minicell treated mice required a 25,000 times (or greater) reduction in chemotherapy while still achieving curative responses. In one noted report mice were cured of cancer using 4 time weekly dosing of 520 ng! I was stunned by these results. Wasn't anyone else?

With minicells, it does not really matter that much what anti-cancer drug is loaded into minicells. Yet, loading minicells with 3-BP, paracetamol and salinomycin might produce interesting results.
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#35 mag1
Posted 01 February 2015 - 06:51 PM The only two accessible published patient reports in humans of 3-BP are noted in my last post.
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It is disgraceful that so many years after the original research was published there is almost no human experience with 3-BP. This extraordinary ignorance puts patients in a very difficult position. If they try the drug with the present minimal information regarding its use in humans they might regret it. The patients reports chosen likely reflect strong positive publication bias. What were the results with other patients who the authors of the papers might also have treated. Should not these details be included in the journal articles? However, given the limited choices presented to many cancer patients, many might feel that 3-BP is there best chance.

I strongly believe that the outcomes in treating patients with 3-BP and other alternative treatments should be required by law to be published. A simple online journal of such reports would be invaluable in helping patients make the best treatment choices.

It has been reported that the Columbian clinic has published a positive report using 3-BP and salinomycin in lung cancer. However, it does not appear to be on pubmed yet. 3-BP is also being used clinically in Germany, though no published reports. The Dayspring clinic has been granted the right to treat with 3-BP, though it is not clear whether anyone has actually received 3-BP treatment from them. The initiation of the American phase 1 trial for 3-BP which was authorized to begin immediate enrolment almost 2 years ago is now being pushed further into 2015 (perhaps the spring).

Edited by mag1, 01 February 2015 - 06:52 PM.


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#36 pone11
Posted 01 February 2015 - 07:34 PM mag1, on 01 Feb 2015 - 7:32 PM, said: The article with the patient with metastatic melanoma showed a fairly modest response when given 8 doses of 3-BP at the recommended dose. However, two combination doses of 3-BP and paracetamol cured the cancer! (see figure 3 from the below url).
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http://www.ncbi.nlm....les/PMC4110469/

The other published human 3-BP patient report noted a very large anti-tumor response to straight 3-BP though at a higher dose than in the above report.

http://www.ncbi.nlm....pubmed/22382780

It should be pointed out that paracetamol is nothing more than acetaminophen. We had a bottle of it lying around and did not even know that this was paracetamol. Is a prescription even required for it?

The readers of this thread are a hard bunch to impress. The cancer compass url that I gave in a earlier post, mentioned that minicell treated mice required a 25,000 times (or greater) reduction in chemotherapy while still achieving curative responses. In one noted report mice were cured of cancer using 4 time weekly dosing of 520 ng! I was stunned by these results. Wasn't anyone else?

With minicells, it does not really matter that much what anti-cancer drug is loaded into minicells. Yet, loading minicells with 3-BP, paracetamol and salinomycin might produce interesting results. Be careful about Figure 3. Figure 3 does not show cancer as cured. Figure 3 shows that LDH went to near-zero levels after the treatments. LDH is a metabolite that is often a good marker for cancer progression.

What was that patient's final outcome? If there were skin cancers that had metastasized why didn't they biopsy the tumor and try to show explicit regression of an established tumor? It's a waste of such a good outcome for them to not go further than measuring a metabolite.

Since you are seriously ambitious about pursuing 3BP, can I suggest you contact the main researchers on that study and ask them about that, and then also ask them about future human trials they are conducting, as well as other groups they know about?

I missed the study on minicells, can you repost the link and summarize what these are and how they work?

What I like about Longecity is that the readers approach EVERY claim with a similar skepticism that a scientist might show, and they evaluate evidence critically. That's a good thing, because it keeps people sharp and it keeps conversations focused on science. On nearly every other health forum I visit, people who cannot read or understand science just throw emotions at each other. Claims with little proof are easily believed, and claims with fantastic proof are easily dismissed. I agree with you this is a hard place to make a point, but generally I find the dynamic much healthier, and people do not waste time on silly claims.

Edited by pone11, 01 February 2015 - 07:37 PM.


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#37 mag1
Posted 01 February 2015 - 09:47 PM From the article regarding the patient with metastatic melanoma"
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"Serum LDH, a good parameter for the evaluation of tumors such as melanoma, is superior to the presence of a residual tumor mass for predicting treatment outcome

... Interestingly, serum LDH level reflects metabolic energy activity of cancer cells inside tumor mass, which may be a more sensitive indicator of tumor activity than tumor size.

... When discussing anticancer effects of 3BP, serum LDH level estimation as a response to treatment is critical, as 3BP is a structural analog of both lactate and pyruvate. Lactate produced through activity of LDH fuels aerobic populations inside tumors via metabolic symbiosis."

The authors are stressing the point that mere tumor burden at death in this patient report is not as relevant as the fact that the tumor mass had lost almost all viability. I am not entirely sure, though it seems quite possible that a tumor mass that had lost its ability to produce lactate is essential destroyed. LDH a widely used biomarker for tumor burden.

It should be emphasized that the near elimination of LDH occurred after only 2 combination treatments.

The below url nicely summarizes 3-BP research. It provides some background on a third successful human patient treated with 3-BP, though no journal reference is given.

https://www.dropbox....view_A.pdf?dl=0

The cancer compass url I posted earlier goes through all the details of minicells treatment. One of the members of the thread is trying to arrange minicell treatment. As you read through the posts (these posts are the recent ones), it turns out that minicell treatment poses surprisingly few obstacles to those with some lab background.

The below url provides a good introduction to minicells. On page 5 of the article, (Figure 1A) notice that 520 nanograms of monastrol 4 times per week loaded onto minicells cured the mice of cancer! NANOGRAMS! A weekly dose of 125,000 ng of free monastrol had almost no effect on slowing tumor volume. Such small doses even below the scale of homeopathy are possible because the minicells specifically target cancer cells.

http://www.tandfonli...61/cc.6.17.4648

Cell Cycle. 2007 Sep 1;6(17):2099-105. Epub 2007 Jun 27. Bacterially-derived nanocells for tumor-targeted delivery of chemotherapeutics and cell cycle inhibitors.

The one emotion that I might throw around on this forum regarding 3-BP is exasperation. How could treating seriously ill cancer patients with drugs that have often proven ineffective be considered ethical when the results from 3-BP appear quite impressive?
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#38 pone11
Posted 01 February 2015 - 11:39 PM
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mag1, on 01 Feb 2015 - 10:47 PM, said: From the article regarding the patient with metastatic melanoma"

"Serum LDH, a good parameter for the evaluation of tumors such as melanoma, is superior to the presence of a residual tumor mass for predicting treatment outcome

... Interestingly, serum LDH level reflects metabolic energy activity of cancer cells inside tumor mass, which may be a more sensitive indicator of tumor activity than tumor size.

... When discussing anticancer effects of 3BP, serum LDH level estimation as a response to treatment is critical, as 3BP is a structural analog of both lactate and pyruvate. Lactate produced through activity of LDH fuels aerobic populations inside tumors via metabolic symbiosis."

The authors are stressing the point that mere tumor burden at death in this patient report is not as relevant as the fact that the tumor mass had lost almost all viability. I am not entirely sure, though it seems quite possible that a tumor mass that had lost its ability to produce lactate is essential destroyed. LDH a widely used biomarker for tumor burden.

It should be emphasized that the near elimination of LDH occurred after only 2 combination treatments.

All clear, and the question still is why didn't they report the tumor mass. It's an odd thing to say that the metabolite better predicts outcome but then not show the outcome.

mag1, on 01 Feb 2015 - 10:47 PM, said: The below url nicely summarizes 3-BP research. It provides some background on a third successful human patient treated with 3-BP, though no journal reference is given.

https://www.dropbox....view_A.pdf?dl=0

The cancer compass url I posted earlier goes through all the details of minicells treatment. One of the members of the thread is trying to arrange minicell treatment. As you read through the posts (these posts are the recent ones), it turns out that minicell treatment poses surprisingly few obstacles to those with some lab background. The one thing I would point out on the study that combines 3BP and Paracetamol is that the data is not as conclusive as you think. With 3BP alone the LDH levels appear to be in steady decline, and then only at about 20 days into the study do they introduce Paracetamol. That really spoils the data. They should have had two separate test groups, one with 3BP only, and one with the two drugs combined from the start. I only read the charts, so maybe I am missing something?

mag1, on 01 Feb 2015 - 10:47 PM, said: The below url provides a good introduction to minicells. On page 5 of the article, (Figure 1A) notice that 520 nanograms of monastrol 4 times per week loaded onto minicells cured the mice of cancer! NANOGRAMS! A weekly dose of 125,000 ng of free monastrol had almost no effect on slowing tumor volume. Such small doses even below the scale of homeopathy are possible because the minicells specifically target cancer cells.

http://www.tandfonli...61/cc.6.17.4648

Cell Cycle. 2007 Sep 1;6(17):2099-105. Epub 2007 Jun 27. Bacterially-derived nanocells for tumor-targeted delivery of chemotherapeutics and cell cycle inhibitors. The minicell approach looks wrong for delivery of 3BP. The entire point of 3BP is that it exploits the fact that cancer cells have these elevated HK2 levels and more pathways into the cell and mitochondria both for delivery of glucose. 3BP is selectively targeting cancer cells by riding through those gateways into the cell. What possible reason would there be to use minicells? The whole point of 3BP is that normal cells won't uptake enough of it to kill their energy metabolism, but cancer cells will. You don't get added benefit through minicells? People should just focus on getting real trials with humans done with 3BP, not wasting time on new science. No new science is required to just test what already exists and seems to work well.

Morever, minicells as they are described are just a package. They are not the trick used to deliver the package, and that is the hard part of the problem. Each cancer has a different way of altering the cell membrane, and you have to figure out what that is *for each type and variation of cancer* and how to use that membrane structure in order to deliver the minicell. That's what cancer scientists have been trying to do for the last 30 years and largely falling on their faces in failure. Many times they develop a drug that selectively delivers into a cancer cell, the cancer cell then evolves over time to overcome that architecture. What makes 3BP unique is that it appears to be utilizing the primary energy pathway for the cancer cell, which the cancer cell cannot evolve away without changing its whole metabolic approach.

Maybe I am not understanding something about how minicells get delivered?

mag1, on 01 Feb 2015 - 10:47 PM, said: The one emotion that I might throw around on this forum regarding 3-BP is exasperation. How could treating seriously ill cancer patients with drugs that have often proven ineffective be considered ethical when the results from 3-BP appear quite impressive? Well, it did not help that the researcher who originally discovered 3BP is claiming it as his proprietary discovery. Many might have been scared away because of threats of litigation.

The system is also very broken because research money is available for proprietary drugs or things that can be turned into proprietary drugs. It could be that some see 3BP as free and therefore not something that can be made proprietary. And those who see it as proprietary are leaving it to the researcher who claims this to get his own funding.

If you really care about this, why not contact the researchers of the study you post, as I suggested? They might know of other human trials and you could start to track those. They might also have a perspective on why more groups are not jumping on this. I already posted about Dominic D'Agostino's group in Florida, and they want to test a different HK2 inhibitor similar in action to 3BP. They cannot get funding, even though they already have very impressive in vitro results. The system is corrupt. It's not about pure science. It's about groups with money finding ways to make money for themselves, and sometimes it is about not funding things that you think might hurt your other interests.

Edited by pone11, 01 February 2015 - 11:55 PM.


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#39 mag1
Posted 02 February 2015 - 12:15 AM The tumor mass itself did not seem relevant to them. It was just a large mass of destroyed tumor cells. LDH is a traditional method to determine whether a determine is actually active. In the 2012 patient report, they noted that none of the cancer cells they found in the patient were viable. There was just liters of fluid of destroyed liver cancer cells.
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The authors consider the decline in 3-BP from over 4000 to 1800 with single 3-BP treatment to be "minimal"

"After ethics committee approval and written patient consent, the patient received 3BP intravenous infusions (1-2.2 mg/kg), but the anticancer effect was minimal as indicated by a high serum LDH level.

...Maximum LDH decrease upon combined treatment confirmed that tumoral GSH was antagonistic to 3BP-induced melanoma cell death. That might indicate a shut down in glycolysis in melanoma cells and signal metabolic cure of metastatic melanoma."

They already knew that 3-BP was not likely to be as effective as a combination would be. They go on to note that previous research had found that 3-BP alone was not sufficient to effectively treat melanoma. It had been found that a GSH depleotr would be needed (e.g. paracetamol).

The minicells allow for dramatic reduction in dosage, the combination with a variety of other medications, and direct targeting to cancer cells. The research has noted that some cancer are resistant to 3-BP treatment because they lack MCT receptors. A cancer would likely never be able to withstand being subjected to 3-BP if it gained entry into the cell. Minicells provide this opportunity because any cancer receptor can be added to the surface of the minicell. There are many receptors to choose from. The bi-specific antibodies on the minicells could be changed and the cancer cell would have no way to defend itself. Cancer cell can shut off entry via MCTs.

The suspicion would be that pharmaceutical companies are working overtime trying to find a better and patentable form of 3-BP. It is possible that they have not been able to accomplish this. Possibly the molecule needs to be as simple as 3-BP to work and perhaps this means that there is a problem making the drug different enough from 3-BP to file a valid patent.

I would be inclined to watch the 3-BP story develop from the sidelines.
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#40 pone11
Posted 02 February 2015 - 01:15 AM mag1, on 02 Feb 2015 - 01:15 AM, said: The tumor mass itself did not seem relevant to them. It was just a large mass of destroyed tumor cells. LDH is a traditional method to determine whether a determine is actually active. In the 2012 patient report, they noted that none of the cancer cells they found in the patient were viable. There was just liters of fluid of destroyed liver cancer cells.
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The authors consider the decline in 3-BP from over 4000 to 1800 with single 3-BP treatment to be "minimal"

"After ethics committee approval and written patient consent, the patient received 3BP intravenous infusions (1-2.2 mg/kg), but the anticancer effect was minimal as indicated by a high serum LDH level.

...Maximum LDH decrease upon combined treatment confirmed that tumoral GSH was antagonistic to 3BP-induced melanoma cell death. That might indicate a shut down in glycolysis in melanoma cells and signal metabolic cure of metastatic melanoma."

They already knew that 3-BP was not likely to be as effective as a combination would be. They go on to note that previous research had found that 3-BP alone was not sufficient to effectively treat melanoma. It had been found that a GSH depleotr would be needed (e.g. paracetamol). Good science requires good experiments. Changing a protocol mid-stream isn't the way you do it in order to record the purest result.

I'm not saying that 3BP is not effective. I'm not saying the combination therapy wasn't better. I'm saying the way they reported it is not great science.

mag1, on 02 Feb 2015 - 01:15 AM, said: The minicells allow for dramatic reduction in dosage, the combination with a variety of other medications, and direct targeting to cancer cells. The research has noted that some cancer are resistant to 3-BP treatment because they lack MCT receptors. A cancer would likely never be able to withstand being subjected to 3-BP if it gained entry into the cell. Minicells provide this opportunity because any cancer receptor can be added to the surface of the minicell. There are many receptors to choose from. The bi-specific antibodies on the minicells could be changed and the cancer cell would have no way to defend itself. Cancer cell can shut off entry via MCTs.

The suspicion would be that pharmaceutical companies are working overtime trying to find a better and patentable form of 3-BP. It is possible that they have not been able to accomplish this. Possibly the molecule needs to be as simple as 3-BP to work and perhaps this means that there is a problem making the drug different enough from 3-BP to file a valid patent.

I would be inclined to watch the 3-BP story develop from the sidelines.

The value of minicells is to deliver massive doses of toxic chemicals in a targeted way, just into cancer cells. 3BP does not need this. They can already get a toxic dose selectively into just cancer cells. Moreover, the presence of 3BP outside of normal cells does not appear to be toxic to those cells. Therefore there is no need to avoid a systemic toxicity with 3BP in the current dosing regimens.

If you had a minicell, what is the mechanism for getting it into the cell? The answer to that would be different for different types of cancers. Why introduce a new problem you didn't have with 3BP alone? Minicells appears to solve a problem that doesn't need to be solved, relative to this particular therapy 3BP.

I contacted the researchers on both of the 3BP studies you posted today. We'll see if they have any information on new studies or on reasons for slow uptake by other researchers.
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#41 mag1
Posted 02 February 2015 - 06:37 PM I am very glad that they did not put science before their ethical obligations. These researchers were able to clearly show that straight 3-BP had a fairly modest effect on the patient's LDH level after several treatments at the given dosage level. They then showed that paracetamol in combination with 3-BP had a very profound and immediate effect on LDH levels after 2 treatments. Science in general (and 3-BP treatment in particular) would be much further advanced if such a more practical (adaptive and moral) scientific approach were used in research. Adaptive designs merely respond to circumstances as they arise. There is no compelling argument to be made that experiments must rigidly continue with an hypothesis that has been shown to be invalid. 3-BP alone was not shown to be overly effective as a single agent at the dosage used in the patient report. There was research that suggested paracetamol would increase its effectiveness. When they did the combination, the result was a much more effective treatment.
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The minicells deliver nanoscale doses directly to cancer cells. 3-BP will only be effective in cancer cells that express MCTs. Not all cancer cells do. Cancer has always had an infuriating ability to become resistant to any treatment. This is why cancer has yet to be cured. If even a single cancer cell becomes resistant to a treatment, then there will be a recurrence. Minicells might get around this problem by allowing 3-BP to enter any cancer cell (even those cancer cells without MCTs). As has been pointed out on this thread, cancer cells likely would not be able to change their primary method of energy metabolism.

Minicells might appear to be a side-issue until it is noted that the patients reported in the published reports had massive responses and were likely selected for publication because of these overwhelming responses. Patients with different patterns of MCT receptor expression might display much less favourable responses to 3-BP treatment. The publication of such disappointing results might hold back 3-BP for many years while the reasons behind such disappointments were investigated.

3-BP is a strong candidate for preventative cancer management. 3-BP enclosed in minicells might allow miniscule doses of the drug to completely prevent the emergence of cancer. It might not be considered ethical or be shown to be effective if it were to be given systemically.
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#42 pone11
Posted 02 February 2015 - 11:15 PM mag1, on 02 Feb 2015 - 7:37 PM, said: The minicells deliver nanoscale doses directly to cancer cells. 3-BP will only be effective in cancer cells that express MCTs. Not all cancer cells do. Cancer has always had an infuriating ability to become resistant to any treatment. This is why cancer has yet to be cured. If even a single cancer cell becomes resistant to a treatment, then there will be a recurrence. Minicells might get around this problem by allowing 3-BP to enter any cancer cell (even those cancer cells without MCTs). As has been pointed out on this thread, cancer cells likely would not be able to change their primary method of energy metabolism.
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Minicells might appear to be a side-issue until it is noted that the patients reported in the published reports had massive responses and were likely selected for publication because of these overwhelming responses. Patients with different patterns of MCT receptor expression might display much less favourable responses to 3-BP treatment. The publication of such disappointing results might hold back 3-BP for many years while the reasons behind such disappointments were investigated.

3-BP is a strong candidate for preventative cancer management. 3-BP enclosed in minicells might allow miniscule doses of the drug to completely prevent the emergence of cancer. It might not be considered ethical or be shown to be effective if it were to be given systemically. I saw one researcher claim that 3BP might treat 95% of all cancers. How about we get the drug tested for those 95% and worry about the 5% later? It's not like there is a flood of 3BP research in humans and we have the resources to dilute that research in so many directions.

I still think you don't seem to understand that most of the 3BP is already going into the cancer cell, and it is staying out of the normal cells. If a drug does not threaten normal cells, and most of it goes into the target cancer cell, what added benefit do you get from minicell encapsulation? You keep trying to solve a problem that doesn't need to be solved, for this drug.

Contrast that to one of the many lethal toxins that are used in chemotherapy. These drugs kill healthy cells, not just cancer cells. For such a drug, there is a huge benefit to the minicell, as a  way to release the toxic payload only inside of a cancer cell. We don't have that problem for 3BP, and your approach doesn't improve effectiveness of 3BP in the cancer cell. It's not clear what problem you want to solve.
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#43 niner
Posted 02 February 2015 - 11:15 PM I'm not sure how much of a cure this was, since the guy died from a cardiac metastatic lesion, leading to hypoxemia. He was reported to have died 12 Oct 2012. Maybe if they had started the treatment earlier, and started the acetaminophen at the same time it might have turned out differently.
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#44 mag1
Posted 03 February 2015 - 12:04 AM The patients selected in the published reports were patients that medicine had nothing left to offer. In both instances the responses the patients had to 3-BP treatment was extreme.
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The German report of liver cancer was extraordinary. The boy would have been offered the best possible options for his treatment. These options showed dim prospects of success using standard treatment. The ethics committee carefully deliberated what should be done. When the decision of the committee was decided in favor of allowing 3-BP treatment, treatment began immediately. There were no side effects. How many chemotherapy patients could say that? When they gave another dose, there were still no immediate side-effects, though later that day the boy went into a coma because there had been an overwhelmingly massive destruction of cancer cells (Tumor lysis syndrome). It is not entirely clear how the doctors had not anticipated such an outcome or why the ethics panel did not require monitoring for such a likely side-effect.

The question that springs to mind is why are not all end stage cancer patients demanding this treatment? Over half a million cancer deaths are expected in America this year! It will not take many more published reports similar to the one from Germany before there is a rush by desperate end stage cancer patients to try it.

The metastatic melanoma patient also had a hopelessly severe cancer burden. It is not difficult to imagine how a conventional oncologist might react if such a patient were thrust unto the doctor for care. Such a patient would have few possible treatment options. The article notes that the patient had run out of treatment choices. This patient also experienced no side effects from treatment and was standing comfortably after his treatments. Dismissing the metabolic cure of the patient with combination 3-BP and peracetamol treatment seems unreasonable. It is not hard to imagine that such a patient could have been saved if a surgical intervention had restored his ability to breathe.

Edited by mag1, 03 February 2015 - 12:06 AM.


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#45 mag1
Posted 03 February 2015 - 12:29 AM The 95% figure for the cancers that 3-BP could treat actually represents 100% of active cancer. The 5% figure given for cancers that could not be treated by 3-BP are those cancers that are metabolically inactive. Such cancers would not be aggressive or possibly even life threatening.
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It should be further noted that in neither of the published reports with 3-BP did the patients actually succumb to cancer even though the illness burden was overwhelming. The metastatic melanoma patient succumbed to hypoxemia and the liver cancer patient succumbed to liver failure. The liver cancer patient had liters of fluid filled with cancer cells. None of the cancer cells were found to be viable.
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#46 pone11
Posted 03 February 2015 - 01:32 AM mag1, on 03 Feb 2015 - 01:04 AM, said: The patients selected in the published reports were patients that medicine had nothing left to offer. In both instances the responses the patients had to 3-BP treatment was extreme.
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The German report of liver cancer was extraordinary. The boy would have been offered the best possible options for his treatment. These options showed dim prospects of success using standard treatment. The ethics committee carefully deliberated what should be done. When the decision of the committee was decided in favor of allowing 3-BP treatment, treatment began immediately. There were no side effects. How many chemotherapy patients could say that? When they gave another dose, there were still no immediate side-effects, though later that day the boy went into a coma because there had been an overwhelmingly massive destruction of cancer cells (Tumor lysis syndrome). It is not entirely clear how the doctors had not anticipated such an outcome or why the ethics panel did not require monitoring for such a likely side-effect.

The question that springs to mind is why are not all end stage cancer patients demanding this treatment? Over half a million cancer deaths are expected in America this year! It will not take many more published reports similar to the one from Germany before there is a rush by desperate end stage cancer patients to try it.

The metastatic melanoma patient also had a hopelessly severe cancer burden. It is not difficult to imagine how a conventional oncologist might react if such a patient were thrust unto the doctor for care. Such a patient would have few possible treatment options. The article notes that the patient had run out of treatment choices. This patient also experienced no side effects from treatment and was standing comfortably after his treatments. Dismissing the metabolic cure of the patient with combination 3-BP and peracetamol treatment seems unreasonable. It is not hard to imagine that such a patient could have been saved if a surgical intervention had restored his ability to breathe. I can't remember which thread mentioned it, but there are new laws sweeping through the US state legislatures now that make it legal for a patient with a terminal illness to seek treatments that the FDA has NOT approved. That's an incredibly important step, but as the sad cases above make clear, when a patient allows the cancer to get too far, the cure can be as bad as the disease. That's no fault of 3BP I guess, and they just need to get experience in not killing too much cancer too quickly. I think that is a good problem to have probably, if the alternative is a therapy that barely stops the growth of the cancer.

Let's hope that patient demand alone forces researchers to start to take 3BP more seriously.

If you had cancer, I wonder if you wouldn't prefer 3BP as the first line treatment. Getting that to happen would be tough.

As an aside, have any of the animal studies looked at using 3BP to treat primary brain cancers? Does 3BP easily cross the blood brain barrier?

mag1, on 03 Feb 2015 - 01:29 AM, said: The 95% figure for the cancers that 3-BP could treat actually represents 100% of active cancer. The 5% figure given for cancers that could not be treated by 3-BP are those cancers that are metabolically inactive. Such cancers would not be aggressive or possibly even life threatening. Okay, so no need for minicells here! And that is great news, because 3BP by itself might be both safe and effective for a wide array of cancers!
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#47 resveratrol_guy
<p class="posted_info desc lighter ipsType_small">Posted 03 February 2015 - 04:42 PM pone11, on 03 Feb 2015 - 02:32 AM, said:
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As an aside, have any of the animal studies looked at using 3BP to treat primary brain cancers? Does 3BP easily cross the blood brain barrier? 3BP might work with brain tumors, with a little help: "C6 glioma transfected with DAO and treated with D-serine together with 3BP-sensitized glioma cells to 3BP and decreased markedly proliferation, clonogenic power and viability in a three-dimensional tumor model with lesser effect on normal astrocytes".

https://www.ncbi.nlm...pubmed/21921941

Obviously there's the Alzheimer's risk to consider as well, if there's any human reality to it. But better that, than glioma.

But let's be honest about this: there are no pharmabucks in 3BP, especially after the patent fiasco, so the odds of getting a clinical trial concluded and published (like the interminably delayed one mentioned above) is essentially zip. And how would you test something this broad, anyway? One cancer at a time, until the next Ice Age?

If 3BP is in any way true to its hype, it will be tested by individuals in desperate situations, at Dayspring or other clinics like the Colombian one. The accumulation of dirty data that comes from those trials-of-one will far outweigh the value of any particular nonhappening "good science" trial with no funding and no route to profits. Obviously patients need to be informed that this substance is still stuck in the lab, but they deserve the choice.

And seriously, we're not talking about finding the boiling point of water here. The data analysis required to do good science, even over the course of decades, would be overwhelming. (And then the nerds would pick it apart with "poorly constructed trial" etc. etc. forever.) The dirty data approach will be faster, and ultimately, save more lives and provide more information. Even if 3BP "only" raises 5-year survival for pancreatic cancer to 10%, that would be a Nobel Prize level accomplishment. OTOH if it's all hot air, then I think that would become rapidly obvious through crowd reporting, probably before this pseudotrial even kicks off. At least, in that case, we'll be off to the next drug candidate while the FDA is still sharpening its pencils.

The reality is probably that 3BP needs assistance from other compounds, along the lines of minicell therapy or the article above. But that's optimization. Let's take what we can get and allow people to try to fix their life-threatening problems. (This goes to the "Right to Try" legislation alluded to above. Right to Try is complicated like any piece of American legislation, but there are certainly elements in it that make good ethical sense.)

I'm not against good science. It's just that biology is too complicated, and cancer moves too quickly. It is no understatement to say that every cancer is a computer trying to solve a molecular problem. It has a gun to your head, and as soon as it figures out how to pull the trigger, it could kill you. Are you going to sit there trying to figure out how the gun works, or start attacking it with everything you have, learning what you can from others who have fought off similar attackers?

Edited by resveratrol_guy, 03 February 2015 - 04:42 PM.


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#48 pone11
<p class="posted_info desc lighter ipsType_small">Posted 03 February 2015 - 06:35 PM resveratrol_guy, on 03 Feb 2015 - 5:42 PM, said:
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pone11, on 03 Feb 2015 - 02:32 AM, said:

As an aside, have any of the animal studies looked at using 3BP to treat primary brain cancers? Does 3BP easily cross the blood brain barrier? 3BP might work with brain tumors, with a little help: "C6 glioma transfected with DAO and treated with D-serine together with 3BP-sensitized glioma cells to 3BP and decreased markedly proliferation, clonogenic power and viability in a three-dimensional tumor model with lesser effect on normal astrocytes".

https://www.ncbi.nlm...pubmed/21921941

Obviously there's the Alzheimer's risk to consider as well, if there's any human reality to it. But better that, than glioma.

But let's be honest about this: there are no pharmabucks in 3BP, especially after the patent fiasco, so the odds of getting a clinical trial concluded and published (like the interminably delayed one mentioned above) is essentially zip. And how would you test something this broad, anyway? One cancer at a time, until the next Ice Age?

If 3BP is in any way true to its hype, it will be tested by individuals in desperate situations, at Dayspring or other clinics like the Colombian one. The accumulation of dirty data that comes from those trials-of-one will far outweigh the value of any particular nonhappening "good science" trial with no funding and no route to profits. Obviously patients need to be informed that this substance is still stuck in the lab, but they deserve the choice.

And seriously, we're not talking about finding the boiling point of water here. The data analysis required to do good science, even over the course of decades, would be overwhelming. (And then the nerds would pick it apart with "poorly constructed trial" etc. etc. forever.) The dirty data approach will be faster, and ultimately, save more lives and provide more information. Even if 3BP "only" raises 5-year survival for pancreatic cancer to 10%, that would be a Nobel Prize level accomplishment. OTOH if it's all hot air, then I think that would become rapidly obvious through crowd reporting, probably before this pseudotrial even kicks off. At least, in that case, we'll be off to the next drug candidate while the FDA is still sharpening its pencils.

The reality is probably that 3BP needs assistance from other compounds, along the lines of minicell therapy or the article above. But that's optimization. Let's take what we can get and allow people to try to fix their life-threatening problems. (This goes to the "Right to Try" legislation alluded to above. Right to Try is complicated like any piece of American legislation, but there are certainly elements in it that make good ethical sense.)

I'm not against good science. It's just that biology is too complicated, and cancer moves too quickly. It is no understatement to say that every cancer is a computer trying to solve a molecular problem. It has a gun to your head, and as soon as it figures out how to pull the trigger, it could kill you. Are you going to sit there trying to figure out how the gun works, or start attacking it with everything you have, learning what you can from others who have fought off similar attackers?

Here is full text for the rat brain cancer study you linked:

http://www.nature.co...cgt201159a.html

How weird that they did not do a lifespan result in that experiment. I get the feeling they treated the rats for a short time and then just killed them to get their data. What a loss to not understand the real effects of the treatment on the overall course of the disease....

I'm all for dirty data. Right to try laws should help researchers who want to conduct such trials to not need approval from the FDA. That's really important to streamlining the process.
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#49 mag1
<p class="posted_info desc lighter ipsType_small">Posted 03 February 2015 - 06:41 PM Tumor Lysis Syndrome is a completely preventable and treatable medical condition. (For example, Prophylactic allopurinol can be prescribed to patients. Kayexalate can be prescribed to reduce serum potassium levels. etc.)
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Minicells might help, though, in avoiding this problem altogether. When giving straight 3BP, there is a real sense that you are riding on a lion. The dosing curves showed that 3-BP has no measurable effect on cancer at small enough doses, though once the therapeutic effect of 3-BP begins there is a rapid dose response. This problem might still need to be worked through, in order that 3-BP could be given safely. Consider that if the metastatic melanoma patient had lived his entire tumor mass had been destroyed. A Tumor lysis response under such conditions would not be unexpected.

However, consider how minicells might help avoid the tumor lysis problem. A minicell with 1 million or more drug molecules certainly would destroy a cancer cell once it gained entry. There would therefore be a linear response over the entire range of therapeutic dosing. It would, thus, be easy to avoid a tumor lysis response with minicells. This is illustrated in Figure 1A from http://www.tandfonli...61/cc.6.17.4648. The dosing in the mice showed how easy it is with minicells to control the cancer elimination process.
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#50 mag1
<p class="posted_info desc lighter ipsType_small">Posted 03 February 2015 - 07:00 PM Does anyone know how to change the tags on this thread? I am not sure whether this can be done once the thread has been created.
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I would like to add the tag "The cure for cancer". So many of the other cancer topics are really not related to curing truly extreme levels of metastatic illness as 3-BP has shown itself capable of. I would like to see whether any other therapeutic with a cancer cure tag could match 3-BP. Perhaps minicells? Car T-cells? Let's throw down the gauntlet and see who steps up.

Changing the tag could really help focus attention on the astonishing anti-cancer properties that have been demonstrated by 3-BP. Most of the other threads with the cancer tag do not appear to offer curative responses for those with severe metastatic illness. I eat my fruits and vegetables and I highly recommend them to others reading this thread. It's just that I do not think they would cure someone with severe metastatic cancer.
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#51 pone11
<p class="posted_info desc lighter ipsType_small">Posted 03 February 2015 - 08:33 PM mag1, on 03 Feb 2015 - 7:41 PM, said: Tumor Lysis Syndrome is a completely preventable and treatable medical condition. (For example, Prophylactic allopurinol can be prescribed to patients. Kayexalate can be prescribed to reduce serum potassium levels. etc.)
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Minicells might help, though, in avoiding this problem altogether. When giving straight 3BP, there is a real sense that you are riding on a lion. The dosing curves showed that 3-BP has no measurable effect on cancer at small enough doses, though once the therapeutic effect of 3-BP begins there is a rapid dose response. This problem might still need to be worked through, in order that 3-BP could be given safely. Consider that if the metastatic melanoma patient had lived his entire tumor mass had been destroyed. A Tumor lysis response under such conditions would not be unexpected.

However, consider how minicells might help avoid the tumor lysis problem. A minicell with 1 million or more drug molecules certainly would destroy a cancer cell once it gained entry. There would therefore be a linear response over the entire range of therapeutic dosing. It would, thus, be easy to avoid a tumor lysis response with minicells. This is illustrated in Figure 1A from http://www.tandfonli...61/cc.6.17.4648. The dosing in the mice showed how easy it is with minicells to control the cancer elimination process. The very first sentence of the abstract from the study you link is:  "Chemotherapeutic drug therapy in cancer is seriously hampered by severe toxicity primarily due to indiscriminate drug distribution and consequent collateral damage to normal cells."

Minicells are about preventing collateral damage to NORMAL cells. They don't change the nature of the death for the cancer cell. Dead is dead. ANY therapy that kills a large enough number of cancer cells at one moment is going to create a tumor lysis problem.

Anyone delivering these 3BP therapies is going to need to become extremely expert at managing tumor lysis. It's about delivering just enough of a dose to kill cancers, and then every few hours monitoring the blood for the byproducts of those dead cells. Once that lysis heads back down, they can then redose 3BP. But does a significant gap between 3BP doses allow the cancer cells to reestablish? How tricky is it in practice to dance between death by living cancer and death by dying cancer?

This is why I can't help but wonder if these 3BP treatments wouldn't have the most value right at the start of cancer treatment, rather than waiting for terminal condition. But getting permission to use 3BP when you are not yet "terminal" might be tough?
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#52 mag1
<p class="posted_info desc lighter ipsType_small">Posted 03 February 2015 - 08:57 PM The point to focus on is that minicells can be dosed in a precise way to destroy exactly the number of cancer cells that would be safe in avoiding tumor lysis syndrome but yet still highly effective.
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Consider this. When you inject 100 minicells loaded with 1 million drug particles into someone with cancer, 30 cancer cells might be destroyed (as per the results of one of the published studies). If you increase the dose 1000 fold to 100,000 minicells you will destroy 30,000 cancer cells. If you increase the dose a further 1000 fold to 100,000,000 (10^10 was the maximum tolerated dose in the human phase 1 trial) minicells, then you will destroy 30,000,000 cancer cells. The number of cancer cells destroyed is completely proportional to minicell dose. Finding the safe dosing range to avoid tumor lysis syndrome would be easy. The number of cancer cells that would create a risk of tumor lysis syndrome is likely a widely known quantity. The mouse study that I referenced in my last post showed how easy it was to use minicells to induce a safe gradual reduction in tumour volumes.

However, injecting straight 3-BP dose not have such a clear linear relationship between dose and cancer cell destruction. Over much of the low end of the dosing range, it does not appear that 3-BP has any appreciable influence on cell survival. A certain minimum threshold of molar dose needs to be reached before 3-BP becomes effective. It seems a more difficult task to precisely determine how many cancer cells will be destroyed for a given dosage of 3-BP. Two doses of paracetamol with 3-BP in the one patient report example resulted in an extreme response. Straight 3-BP appears to be a powerful yet currently somewhat unpredictable treatment. It will likely not require extensive experience with it to figure out the correct dosing, though it does highlight the dangers that could arise from treatment by the do it yourselfers.
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#53 mag1
<p class="posted_info desc lighter ipsType_small">Posted 03 February 2015 - 09:40 PM It is particularly interesting to reread the patient report from Germany. It does not seem outrageous to suggest that the patient's ultimate demise might be related to tumor lysis syndrome. Figure 3 show that after the 10th 3-BP treatment the patient experienced the highest level of urea noted in the figure.
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From the article "About 1 l of ascites fluid was removed and sent to the pathology lab for cellular analysis. ... This lack of tumor cells in the ascites suggested that the tumors in the liver were well encapsulated and dead. In December 2009 the edema and ascites were becoming more problematic. Liver functions were over-loaded due to rapid destruction of the tumor cells resulting in the liver’s inefficient detoxification. ...The patient passed away 2 years after his first diagnosis due to an overload of liver function."

This is quite startling and revealing about the problems related to 3-BP treatment. Even with 11 months of 3-BP treatment the excess of cancer cell destruction was causing severe medical problems. More than any other factor, the inability to carefully control the rate of cancer cell destruction was likely the central contributing factor in the boy's demise. The doctors in his treatment were very well of tumor lysis syndrome at this point and likely had considerable medical expertise to draw upon concerning TLS, though this still largely was insufficient to create a more favourable result.

As the article further notes in the conclusion : "The rate of tumor necrosis due to 3BP treatment seems to exceed all known cytostatic drugs." If this unprecedented power of 3-BP to destroy cancer cells is not tamed, then the potential of 3-BP might be lost.

Questions arise to the strategy used with the patient. The article notes that the cancer had largely disappeared from the patient. The scans show a startling regression of his tumors. Why was it felt necessary to continue to aggressively destroy more tumor mass at the tenth dose? The patient was already overwhelmed by destroyed tumor cells. Giving his body time to clear the cancer cells that had already been destroyed would, in retrospect, have been a much better strategy.
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#54 pone11
<p class="posted_info desc lighter ipsType_small">Posted 03 February 2015 - 10:02 PM mag1, on 03 Feb 2015 - 9:57 PM, said: The point to focus on is that minicells can be dosed in a precise way to destroy exactly the number of cancer cells that would be safe in avoiding tumor lysis syndrome but yet still highly effective.
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Consider this. When you inject 100 minicells loaded with 1 million drug particles into someone with cancer, 30 cancer cells might be destroyed (as per the results of one of the published studies). If you increase the dose 1000 fold to 100,000 minicells you will destroy 30,000 cancer cells. If you increase the dose a further 1000 fold to 100,000,000 (10^10 was the maximum tolerated dose in the human phase 1 trial) minicells, then you will destroy 30,000,000 cancer cells. The number of cancer cells destroyed is completely proportional to minicell dose. Finding the safe dosing range to avoid tumor lysis syndrome would be easy. The number of cancer cells that would create a risk of tumor lysis syndrome is likely a widely known quantity. The mouse study that I referenced in my last post showed how easy it was to use minicells to induce a safe gradual reduction in tumour volumes.

However, injecting straight 3-BP dose not have such a clear linear relationship between dose and cancer cell destruction. Over much of the low end of the dosing range, it does not appear that 3-BP has any appreciable influence on cell survival. A certain minimum threshold of molar dose needs to be reached before 3-BP becomes effective. It seems a more difficult task to precisely determine how many cancer cells will be destroyed for a given dosage of 3-BP. Two doses of paracetamol with 3-BP in the one patient report example resulted in an extreme response. Straight 3-BP appears to be a powerful yet currently somewhat unpredictable treatment. It will likely not require extensive experience with it to figure out the correct dosing, though it does highlight the dangers that could arise from treatment by the do it yourselfers. Ah, the point you want to make here is that you can deliver a lethal dose to less than 100% of all the cancer cells. If you dose 3BP systemically, you run a risk of either having no effect on any cell, or massively killing many cells at once. A good analogy might be that you want to shoot 30 rats in a room filled with 300 rats. Minicells might let you use 30 bullets to kill 30 rats. Systemic dosing of 3BP might be more like exposing all 300 rats to a toxin like a poison gas. Potentially you end up killing 150+ rats all at once.

So for the patient with a small tumor load, systemic use of 3BP might be okay. For a patient with a terminal condition and high tumor load, minicells might give you a way to limit the collateral damage of tumor lysis by killing off less than 100% of the cancer on each dosing.

Edited by pone11, 03 February 2015 - 10:15 PM.


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#55 pone11
<p class="posted_info desc lighter ipsType_small">Posted 03 February 2015 - 10:05 PM mag1, on 03 Feb 2015 - 10:40 PM, said: Questions arise to the strategy used with the patient. The article notes that the cancer had largely disappeared from the patient. The scans show a startling regression of his tumors. Why was it felt necessary to continue to aggressively destroy more tumor mass at the tenth dose? The patient was already overwhelmed by destroyed tumor cells. Giving his body time to clear the cancer cells that had already been destroyed would, in retrospect, have been a much better strategy. I agree, but it is easy to say and *maybe* it is very hard to do. Someone who is familiar with tumor lysis might be able to add nuance to this.
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#56 mag1
<p class="posted_info desc lighter ipsType_small">Posted 03 February 2015 - 10:14 PM The important point to note is that the article reports that the boy succumbed to liver overload not cancer. There was no reason to push more 3-BP at the tenth dose.
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Given the scans from the article it is reasonably clear that the cancer had been well controlled if not cured. Why did they feel it necessary to continue destroying cancer cells? Figure 4D shows a clear control of his cancer while also showing a substantial amount of ascites.
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#57 pone11
<p class="posted_info desc lighter ipsType_small">Posted 03 February 2015 - 10:29 PM mag1, on 03 Feb 2015 - 11:14 PM, said: The important point to note is that the article reports that the boy succumbed to liver overload not cancer. There was no reason to push more 3-BP at the tenth dose.
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Given the scans from the article it is reasonably clear that the cancer had been well controlled if not cured. Why did they feel it necessary to continue destroying cancer cells? Figure 4D shows a clear control of his cancer while also showing a substantial amount of ascites. The only points I can think of off the top of my head (and it's pure speculation):


 * There are not a lot of people with experience in this area, since no one ever "cures" metastatic liver cancer!   Literally, the doctors might have been getting their very first clinical experience in this level of tumor lysis.


 * They might have been researchers more than clinicians, and maybe they were a little too focused on measuring cancer load and not focused enough on measuring patient well being.

Has anyone looked at using 3BP as a prophylactic? It would be interesting to maybe transfuse it once a year into a healthy person, and monitor the byproducts that are excreted over the next month. For most people it would have no effect because there is no cancer. For those with early stage cancers, it might simultaneously kill the cancer while it is in an early stage, as well as act as a diagnostic tool for the presence of cancer by virtue of the presence of lysis byproducts appearing after the infusion.
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#58 mag1
<p class="posted_info desc lighter ipsType_small">Posted 03 February 2015 - 10:54 PM It raises substantial questions concerning medical competency. This is all the more surprising as there was an ethics oversight committee that presumably was in place to ensure that the best interests of the patient would be the primary consideration and not exploring maximal dosing of 3-BP.
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It should be noted that the 3-BP treatment was a substantial success for the patient. Before treatment: "By now, the health condition of the patient had deteriorated, in fact, so far that he could not consume sufficient amounts of food to sustain life... While the patient’s health was deteriorating,...". When 3-BP treatment was started the patient had no obvious treatment options and it might be an exaggeration to suggest that his life expectancy was measured in even weeks. With 3-BP treatment, the patient lived about 11 months with a reasonably high quality of life. The patient "was able to survive a much longer period than expected with an improved quality of life, which is clearly attributable to the treatment with 3BP."

By fully acknowledging that 3-BP treatment in this instance resulted in an overwhelmingly more favorable result, it might encourage others in a similar circumstance to seek such treatment and advance this mode of treatment for those with extremely severe illness. Once it has been widely understood that such cancers benefit from this treatment, earlier interventions might be shown to be even more helpful. It should be noted that large numbers of patients do exist in such extreme end stages of cancer and clinical trials including such patients could lead to rapid clinical results.

Perhaps a 3-BP clinical trial could be conducted in patients with life expectancies of days. Results of such trials might be available in weeks. It is quite possible that such trials could demonstrate statistically significant improvements in survival. Many cancer trials require 5 or more years to generate results which often result in uncertain read outs. For example only with a certain sub-group at a certain stage of cancer or genotype might benefit. Further trials are often required taking yet more years.
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#59 mag1
<p class="posted_info desc lighter ipsType_small">Posted 04 February 2015 - 08:47 PM
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"About 1 l of ascites fluid was removed and sent to the pathology lab for cellular analysis. An outcome of an increased lymphocyte count with some mesothelial cells, but no malignant cells was obtained. This lack of tumor cells in the ascites suggested that the tumors in the liver were well encapsulated and dead."

A translational study “case report” on the small molecule “energy blocker” 3-bromopyruvate (3BP) as a potent anticancer agent: from bench side to bedside J Bioenerg Biomembr (2012) 44:163–170

This is a more complete quote than the one posted above.

This is startling. The article described the patient as having incurable liver cancer as February 2009. In October 2009, the above quote notes that no live tumor cells were found in 1 liter of ascites and apparently the liver tumors might have been destroyed. It would be very interesting to know how much tumor burden was present at that time (from an LDH measurement or a scan). The scans shown in the article show substantial remissions of the tumor masses.*Quote
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Advert:Advertise on LongeCity===#60 resveratrol_guy=== <p class="posted_info desc lighter ipsType_small">Posted 05 February 2015 - 02:05 AM I met yet another pancreatic cancer patient (early stage, poor guy working a low-end job), so I dug this up for him and whom it may concern. (Pancreatic is perhaps the best test of all generalized anticancer therapies, on account of its hardwall tumors resistant to chemotherapy penetration, and tragically, it's abysmal 5-year survival rate.)
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I have more to say but I'm outta time for the moment. This thread is freaking brilliant, so keep it coming, people. I had no idea how ignorant I was about all this. Don't worry about the keywords. Google sees all.

"The microencapsulation of 3-BrPA represents a promising step towards achieving the goal of systemically deliverable antiglycolytic tumor therapy. The strong anticancer effects of β-CD-3-BrPA combined with its favorable toxicity profile suggest that clinical trials, particularly in patients with [pancreatic ductal adenocarcinoma], should be considered." https://www.ncbi.nlm...pubmed/25326230

"We conclude that: i) concurrent use of 2-DG and 3-BrPA has better anticancer effects in pancreatic cancer cells, ii) 3-BrPA impairs the mitochondria of pancreatic cancer cells and induces cell necrosis, and iii) HIF-1α regulates the anticancer effects of 2-DG and 3-BrPA in pancreatic cancer cells." https://www.ncbi.nlm...pubmed/23076497

"The results show that the inhibitors lowered cellular survival and increased cellular necrosis. Mitogenic signaling pathways were affected by 3BP but not by IAA." https://www.ncbi.nlm...pubmed/20392992

^ 2010 -- ignored or WTF?!

"Treatment with the anti-glycolytic agent 3-bromopyruvate almost completely blocked cell viability, self-renewal potential, NF-κB binding activity, and stem cell-related signaling and reverted gemcitabine resistance", i.e. restored tumor vulnerability to the #1 most effective pancreatic cancer drug. Try https://tinyurl.com/oyfm7kt if the link below doesn't work.

http://www.impactjou...iew&path[=2120]

Edited by resveratrol_guy, 05 February 2015 - 02:16 AM.