During the past days I was “forced” to go back to 3BP and think more about it in the context in which I hear more and more about people who are responding but even more important people not responding (out of which some very good friends …).
Actually, when I hear about patients/friends not responding to 3BP, I start to loose my trust in 3BP but than I went back to our file and saw the response so clear in the blood test in our case, during every cycle of 3BP we had (response to one cycle even visible on CT). And than the trust comes back and with that the question WHY? [Note, now we are using Diflunisal (next to many others including some immunotheraphies), which seems to show response. After the Diflu cycle, we will probably go back to 3BP if appropriate and depending on what my wife likes]
In the end, we are battling the challenge of humanity, i.e. cancer. Fighting in a field where the conventional medicine of this world could not help us … and so far successfully.
Back to the question WHY. I know that this question is constantly in the mind of some great scientists involved in the 3BP research. Why some people are responding and some not? Of course, there can be so many explanations, that include blood type, tumor perfusion, MCT expression, 3BP administration strategy and stability of the specific formulation … and so on … However, I feel the main answer is connected to the following statement I came across while reading some patents on Diflu: “Thus each type of tumor has an intrinsic average intercellular pH, which, for example, in the case of breast tumors is about 6.7 and in the case of colon tumors about 6.9.” Ref
The interesting point is that this statement or piece of information may be the right link between two facts:
- A pattern that seems to emerge from all the outcomes we hear of following 3BP treatment, i.e. most of the responding patients are breast cancer patients. (And many of which are simply using the oral administration strategy mainly.) Next to that one prostate, one melanoma, one adrenal, one lung, one pancreas, two liver (but these liver cases were TACE which may be seen as forced and direct administration and should not be compared to the others – my personal opinion). I am not sure about others but at least this is what comes to my mind in terms of most relevant cases.
. - Recently, we have seen an article published stating that 3BP transport is higher when the extracellular milieu is acidic:
The cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH:At pH6.0, the affinity of cancer cells for 3BP transport correlates with their sensitivity, a pattern that does not occur at pH7.4. In the three cell lines, the uptake of 3BP is dependent on the protonmotive force and is decreased by MCTs (monocarboxylate transporters) inhibitors. In the SK-BR-3 cell line, a sodium-dependent transport also occurs. Butyrate promotes the localization of MCT-1 at the plasma membrane and increases the level of MCT-4 expression, leading to a higher sensitivity for 3BP … We find that the affinity for 3BP transport is higher when the extracellular milieu is acidic. This is a typical phenotype of tumour microenvironment and explains the lack of secondary effects of 3BP already described in invivo studies [Ko et al. (2004) Biochem. Biophys. Res. Commun. 324, 269-275].
Yes, while it needs to be investigated further, it is probably the extracellular pH that makes the difference. And breast cancer seems to be one that is characterized by an even lower extracellular pH and this may facilitate the transport of 3BP inside the cancer cells. What are the other cancers characterized by an more acidic tumor environment? That remains to be further investigated. However,this could be a way to select patients that are likely to respond to 3BP treatment. Since the extracellular pH is inverse proportional with the glycolysis (i.e. the higher the glycolisis, the lower the extracellular pH will be) a simple way to identify potential respondents to 3BP is to use PET scan intensity as a reference (however, as discussed here, we need to remember that in my view besides low extracellular pH there is a need for Oxygen as well in order to have the cancer cells able to be fueled by lactate).
Yes, MCT transporters are highly dependent on pH. Transport rates are increased over 10-fold by lowering the pH one unit from 7.4 to 6.4. (Ref.) And as we know, the transporters used by 3BP to enter the cancer cells are the MCTs.
As discussed in other 3BP-related articles on this website, getting response is the first challenge. Maintaining that is another challenge that needs to be addressed together with other drugs, including angiogenesis inhibitors and glycoinhibitors.
Other references:
Disclaimer: https://www.cancertreatmentsresearch.com/?p=1735
I have a supply of 3BP in the fridge waiting for me to figure out how to utilize it in my wife’s ovarian cancer therapies. Her cancer lurks in the abdomen with numerous mesentery implants of concern. We’ve kept it at bay 6 1/2 years with various chemos, HBOT, IVC, ketogenic diet, supplements, off-labels and on and on but it’s still there.
I initially thought IV 3BP might be the way to go but never understood how it could survive the long trip through tightly regulated, slightly alkaline blood. Lately, and after reading your recent thoughts, I think oral and topical might be more appropriate. I believe the path from stomach to colon is acidic to very acidic. We’re constantly aware of how close the cancer is to the GI tract and with my limited grasp of how the 3BP would be utilized, I like the fact it can go straight to the cancer’s neighborhood.
One other point. To date I’ve piled on more and more therapies as the years go by, driving my poor dear wife a little crazy with it all. I like the way you seem to vary the attack, dropping one therapy as you start another and then going back. I’m going to be looking at that.
What about cannabis oil? I am seeing more people using it effectively than any other protocol.
What do you mean Bernhard with seeing more people using it effectively? Do you know more people having good response or you are referring to the info on the web?
(In my opinion, cannabis oil has indeed serious science behind and it may be effective for some.)
Where does one get 3-BP? I have a similar story with Ovarian Cancer, 5 years.
I am glad it helps Fred. I remember RGCC suggesting many clinics would alternate their (effective) treatments switching every two weeks to one month in order to avoid build up of resistance.
Daniel, I’m still trying to decide on which way to go with 3BP. My wife recently developed shingles, disappointing because her tumor marker was quickly dropping under a new half-dose Taxol regimen. We had to shut down chemo for three weeks. During this time she developed a good amount of ascites fluid in the abdomen. We don’t know if it is a product of cancer or the shingles. If it is malignant ascites it is not good sign. We need to quickly become more aggressive.
If we administer 3BP orally it will go straight to the stomach/GI. From there the path of 3BP to the abdominal implants and ascites is a mystery to me. Frustrating because the cancer is in the abdomen, inches away. I’m an audio engineer but not afraid to ask very stupid questions. You’ve presented an oral administration which seems very straightforward and topical/DMSO which is also interesting. Would these two methods have a chance or do you see IV as the most efficient approach. I am setup to do IV-3BP, HBOT, IV-C.
Reading your thoughts above I wondered about the ovarian tumor cell environment. While the following paper is more concerned with imaging, it seems to suggest it the ovarian tumor intracellular pH is >7.0 and the extracellular pH is <7.0, potentially good for 3BP:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533099/
I have a tentative 3 week 3BP cycle I can email if you're interested. As always, I'm looking for any quick thoughts you might have (I know you have your own battles).
Daniel,
I like your theory on pH. I also would like to re-emphasize one of the possibilities you’ve pointed out: MCT1 expression levels in different tissues. You can find it online (free access) Nature Genetics, 45:104-108. Birosy et al. MCT-1mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors. The data is in the supplemental section.
Tanks for the suggestion Tom. I went through that paper before but somehow I never read the supplemental section. After your suggestion, I found it here http://sabatinilab.wi.mit.edu/pubs/SUPPLEMENTARY/suppbirsoy.pdf and on page 7 it shows the relative expression of MCT1 in cancer cell lines and their normal tissue of origins. There are many points you can get from there but one point I would conclude based on this overview is that nebulizing 3BP should be relatively safe since the lung normal tissue shows much lower level compared to its cancer cell line (assuming the 3BP dose is applied from low to the levels of response). Also, if the results are correct than normal colon tissue may be affected by 3BP as a side effect. What do you think?
Yes, colon would be the most affected organ.
Fred,
You can do both, i.e, one followed by another with a few hours of rest or supporting measures in between, e.g., the HBOT you have in your garage or high dose vit C. It’s been done before.
has any body used 5BP for lymphoma or leukemia?
sorry, should be 3BP
Hey, Jurgen.
3-BrOP is highly similar to 3-BP ( it simply adds a few carbons on one end).
3-BrOP has been found to be quite effective with leukemia and lymphoma.
It is not clear whether MD Anderson intends to move it forward.
http://www.cancercuremedicine.com/news-md-anderson-3-brop-or-glycolysin.html
Dear Daniel,
I would like to request your ideas and help concerning the use of 3BP for High Grade Serous Ovarian CA . Diagnosed 1 1/2 years ago-numerous surgeries, 6 months chemo with Gemzar and Cisplat. Just had large incisional hernia repair. Went back for 1 month follow up to learn 2 areas were showing tumor growth/enlargement. One in the left subphrenic area and one above my belly button near the peritoneum. I believe the 3BP may hold promise. Doc at MD Anderson recommends starting more chemo but I am hoping to do something less toxic. What would be the best delivery? Are there any DR.s anywhere in the world you could recommend that could actively treat me? Do you know of any HGSOC patients who have been treated successfully? Thank you.
Dear Sylvia,
I am sorry to hear about the challenges you went through and hope from now on will only go well.
For 3BP specifically, I can only recommend Dayspring https://www.cancertreatmentsresearch.com/?page_id=409
For 3BP and many beyond that I would consider Dr. Jason Williams https://www.cancertreatmentsresearch.com/?page_id=409 but that is an expensive option.
On 3BP line, I would also contact dr. Ko Young as she may start (or already started) clinical trials in a few places across the world, including administration via TACE. For her e-mail address check my post on 3BP https://www.cancertreatmentsresearch.com/?p=47
If you decide to go further with chemo, reading this may help https://www.cancertreatmentsresearch.com/?p=970
For ovarian issues, Salinomycin may make very much sense also combined with chemo https://www.cancertreatmentsresearch.com/?p=49
Beyond this there are various other treatments that may be relevant (some already discussed on this website) so if you have more questions just send me an e-mail.
All the best,
Daniel
Hi Daniel,
Thanks for your research. Do you have any more information on whether Dr. Ko is beginning clinical trials? I have emailed her but have not heard back yet. And along those lines, do you know if it has effectiveness with treating multiple myeloma? Thank you again.
Dear Dana,
You are very welcome. I have no recent info on dr. Ko’s progression with the clinical trials on 3BP and indeed she is usually not responding e-mails. Best would be if you can call her. Based on some literature also added here https://www.cancertreatmentsresearch.com/?p=1306 3BP is expected to be effective in MM.
Kind regards,
Daniel
Unconfirmed report of a 3-BP incident at Dayspring.
https://www.reddit.com/user/letoullec/comments/7v1un0/did_the_experimental_cancer_drug_3bromopyruvate/
hi J,
i know its early to say, but it could easily be tumor lysis syndrome. 🙁
Totally agree. All the signs of what happened in Germany suggest TLS, and this unfortunate event fits to that and is potentially a result of hepatic comma. Same happened to the Dutch boy first time treated with 3BP at Frankfurt Hospital (based on what I discussed with his father – a scientist in bio).
I am not sure about this.
With Bracht, once the incident was reported there was worldwide coverage.
When I checked online, the story was covered extensively by mainstream media and the blogosphere.
The tragedy of Bracht likely created many millions of “media impressions” and to a certain extent moved 3-BP
into mass consciousness.
With this purported incident at Dayspring I have not found any other references other than the unconfirmed report above from reddit. This seems suspicious to me.
Dayspring has recently begun to make more strenuous assertions regarding the efficacy of 3-BP.
For instance, in the last several days they uploaded videos to their testimonies section of patients that describe their 3-BP experience. http://www.dayspringcancerclinic.com/3-bromopyruvate-and-dayspring-cancer-clinic/testimony/
Also, this article published on Cancer Tutor on February 1st, asserts that 3-BP gives patients long term benefit. I had not been entirely clear whether this would be true; others with medical expertise who have treated with 3-BP have encountered problems with resistance.
“Dayspring adds complementary therapies to the 3BP protocol. This helps detoxify the body and enhance immune function. Together, this treatment helps the body re-establish long-term health. This is not a short-term extension of life.” https://www.cancertutor.com/3bp-detox-immune/
Good point J. I will check if this is true.
D, I noticed the other day that there was a surge of new members on the site over the last day or so. Is this true? For some reason I am not able to access this information now, though when I looked yesterday there was about 15 new members that recently joined on one day.
Am I reading this correctly?
The investigators do not think that there was a problem with 3-BP?
I guess that would obviously have been an easy thing to have discovered right away.
Where does this leave us?
Incorrect formulation or TLS?
https://www.abda.de/amk-nachricht/artikel/0518-informationen-der-institutionen-und-behoerden-amk-beurteilung-von-rezepturarzneimitteln-mit-u/print.htm
Hi J, thank you. Interesting link. Yes, it seems that is what they state. So, that is a step forward in terms of understanding possible origin of the problem. Based on knowledge from various sources I strongly believe the origin of the unfortunate events was TLS. In any case, I used 3BP for about 2 years in cycles with no issues, so I am positively biased. 🙂
Btw, I succeeded to find a good developer who solved the tech issues with the website and I am very happy with that 🙂
D, TLS?
I want to be sure on this.
If this is TLS, then this completely redefines the narrative of Bracht.
Basically, if it is TLS, then 3-BP becomes essentially a cure for a broad segment of cancer patients. In the incident 3 of 5 patients developed this response.
In light of this it almost starts to seem that the slowness of the investigation could be thought of as a way of covering up this truth.
Can we really be that sure?
This is a headline worthy finding!
The first global wave of 3-BP coverage was that it caused severe side effects. Yet, a second wave of 3-BP coverage might now proclaim that 3-BP did not cause so much as severe side effects as curative responses that were not properly medically managed.
This is a very very large development if it can be substantiated.
Yes, J, all the evidence from what I see leads to the same, i.e. TLS. Patients in Germany 2016, young patient in Germany at Frankfurt University, and one other patient in South Africa I know (who used 5-10x higher dose by mistake) all had signs of TLS. It’s a lot to say but to me the conclusion, based on many pieces of the puzzle, is that 3BP acts the best against cancer cells with the first IVs and that effectiveness depends on the dose. The effectiveness could be even dangerous at the beginning, when the tumor sees first time 3BP. That is why we need clinical trials …
D, this is a dramatic development!
D, do you have any sense when this might break in the media? We could have dramatic headlines. When people truly understand what this means —there could be a panic. The initial Bracht headlines went viral; the new interpretation could as well.
Are they trying to hush this up? Do they want people not to know the truth? Exactly how could they stop people now? Yet, at the same time I agree that this probably needs to move to a more controlled context. Giving higher doses would be more dangerous and would require TLS monitoring.
This also raises the question of how the hospitals that received the patients responded. Did they not treat them for TLS symptoms? That is hard to imagine!!! If you go back to our first off thread emails about this I think we talked immediately about the potential for TLS. Would the doctors not have actually thought of this?
In retrospect it does start to fit into place. If this were a “poisonous” response due to a bad formulation, then why did not all the patients have severe side effects? It, of course, makes perfect sense that not all the patients would develop TLS even if they were given quite high doses as some would not be expected to respond even at such doses.
I want to put this out there, though I want to give the investigators at least a chance to prepare a response.
How will they respond when we start putting out the headline that 3-BP IS the CURE for CANCER?
If this is in fact what they found, then it would difficult for them to counter such a conclusion.
The question of therapeutic index does certainly arise. How fine a line might there be between destroying cancer and having a fatal response in the patient due to shutting down glycolysis more broadly?
Of course with medicine they always want a fair amount of wiggle room so that giving somewhat more will not cause severe side effects. Thus, the suggested dosing range was possibly just below the curative dosing. We also noted right off that the Bracht dosing did seem somewhat aggressive; I was surprised when they started to move up to somewhere near 3 mg/kg. That seemed dangerous and outside of what had been the norm.
Something else that seems strange to me.
If I recall correctly, at least some of the patients did make it to hospital alive, though some time later some of them expired.
Wouldn’t these patients have had every imaginable test done on them? Shouldn’t TLS be an obvious diagnosis if not at the time at least subsequently when the labs were all assembled? How could this possibly have taken 2 years for this to have been brought to light?
If this were TLS, meaning that 3-BP is essentially a potentially curative treatment for some terminal cancer patients under strict medical observation, then should not this have been made clear to the public much sooner than this? Is it ethical to withhold such information from the millions of people who have passed away from cancer over the last 2 years while this has been investigated?
HI J,
I do not remember the details anymore but from what I recall they used up to 5mg/kg. I think (but it is speculation until proven otherwise) the issue was related to the fact that, the doctor who started like one year before the incident with 3BP, he became confident on it and was pushing the dose higher and higher since he only saw response in some patients and he wanted to help more. Then, as reported by patients, there was some time frame when he did not had 3BP anymore but he was accumulating new patients. Next, he has access again to 3BP and starts to give to the new patients but he starts with those at the same dose as he was given to “old”patients, that is ~5mg/kg. From what I also heard, the new patients were in a very challenging state, such that no other clinic would accept them while the hospital send them home to die.
Now imagine you combine the following:
– patients with high tumor load
– a treatment that is the most effective in the first phase of the treatment (i explained elsewhere why this happens and I have both theory and facts to support)
– patients new to the treatment
– very high dose of the effective treatment
What you can expect in this case is clearly a high amount of TLS.
Now, add to the above the fact that most advanced cancer patients have their liver already under high pressure due to the tumor load (constantly also generating lysis).
Finally you have high TLS in under performing liver. This is the best formula for hepatic coma.
What is expected when hepatic coma occurs? Patients will start vomiting and if the ammonia is at too high level that would go directly to the brain (which is to be expected since the liver dose not do its job well – in healthy people the liver will convert ammonia into urea). Ammonia in turn will lead to shrinkage of the brain cells and can be fatal. What is only known in academic space is that in this case the diuretic medicine Bumetanide (Burinex) can help https://www.med.uio.no/imb/english/research/news-and-events/news/2014/when-ammonia-becomes-toxic.html Now I realize I should send this info to the Dayspring clinic as it is useful to know.
To my knowledge, vomiting and brain issues are two aspects often cited as experienced by the patients at the German clinic in the summer of 2016. And I have one more case in mind fitting perfectly to all the points above (high tumor load + first time 3BP + directly high IV dose (they made a mistake), leading to vomiting).
I do not think anyone will actually state 3BP is the cure for cancer since it is not the responsibility of the investigation team to make such a claim. And I think this is very fair to expect. Such a claim can only be ethically done when there is enough evidence. The only ethical and fair claim that can be done at this point is that based on the evidence generated so far (science and case reports), 3BP seems to have the potential to stand above the conventional cancer treatments available today. But in order to convert that potential in an actually usable tool, clinical trials are required.
Unfortunately for the industry and as a result for the patients, 3BP effectiveness can be achieved even by those not skilled in the art and the substance it is easy accessible (I know this sounds strange). So from the ownership point of view, there is no unique aspect that could be converted in Intellectual Property and represent a barrier to entry for competitors. That is of course not attractive to major industry players. Yet, it could be attractive to smaller players. A little hope on this line: I was contacted by potential investors in 3BP who are now doing their due diligence at this point. Let’s hope one day it goes to the clinical trials. Hopefully during this life time ….
At least we are doing our job hear to create awareness about it, collecting and sharing facts + a bit of speculation from our side around that subject.
Kind regards,
Daniel
D, has there been any response yet in German media?
Finder has said that Dutch media is following this story very carefully. If 3-BP caused fatal TLS in 3 of 5 patients treated in Bracht, then would this not be worthy of a headline? This should mean that with proper medical management 3-BP will possibly be a cancer cure for terminally ill patients.
At what point would this become an investigation of the investigators? 8 million people succumb to cancer every year. Is there not an ethical and legal duty to humanity to report in a prompt manner information that might prevent such tragedies? If the investigators have evidence that the Bracht patients underwent a TLS response then this should be publicly disclosed.
I haven’t seen anything new, J. I hope and expect that when relevant info will be found, that will be presented to the public. However, after so long time researching and discussing 3BP here and on CancerCompass, as well as the learning from using it, I think we do have enough information to judge the potential of 3BP.
Btw, I do not know what the developer that I hired change with this website but now it doesn’t come up on Google searches … so still some things to address with this website …
D, if Bracht was TLS this IS big news for 3-BP.
We have not been sure about this question for the last two years.
As soon as this becomes confirmed then we will start
posting: “3-BP is the cure for cancer!”. I am not sure why Dutch media have not picked up on this yet.
If the three people from Bracht who had fatal TLS responses from 3-BP, then their labs should confirm this. If they did confirm this, then there would be another media whirlwind as 3-BP as announced as a cancer cure. If the side effects caused by 3-BP at Bracht were not related to TLS, but something else, then at least they could eliminate the TLS possibility.
So, either 3-BP is the cure or it isn’t.
Why have we not already experienced a viral media wave on this?
Hi J,
Based on my experience, this is not that black and white, like 3-BP is the cure or it isn’t. So far we have seen that in some context which we think we understand partially, 3BP shows anti cancer effects. But in other cases it doesn’t, even in patients who saw response to prior treatment. Maybe the solution is to attack from beginning with higher dose 3BP but then be in a hospital that is ready to fight TLS. Things are a bit more complex, and that is why we need a combo of clinical trials + deep and focus research. The question now is how we can enable that as it requires important financial support?
Kind regards,
Daniel
D, what I was thinking more is that in the Netherlands this is top news. We have had thread conversations about 3-BP for years. I am wondering what happens when the TLS interpretation reaches the front page?
The interest in 3-BP treatment in the Netherlands and elsewhere would likely become intense. There would then need to be thought given to how this could be scaled up in a safe manner.
I have some doubts about TLS being the cause for (all) the deaths, because 3BP shouldn’t be able alone to cause that. It would be useful to find out if the patients also took a glutaminolysis inhibitor, a glutathione depleting agent, or had high expression on monocarboxylate transporter 1.
ovidiu, thank you commenting.
Usually when I reach a panic point I am no longer able to think clearly anymore.
I am glad that you are still able to think critically about this.
Yet, the TLS theory is starting to congeal for me. The url I posted noted that the 3-BP has been reported by the media to be pure. This shuts down one important avenue of possibilities and redirects us to think what else it could have been. TLS does start to make sense. As D noted the worker at Bracht was pushing 3-BP hoping for better responses. This was well outside of what we had been accustomed to. He was also treating with all sorts of other alternatives such as curcumin which is a strong GLO1 inhibitor. It does start to seem quite possible that this could all converge on TLS. Things would all converge and there would be no sense that such a response should have been expected beforehand.
Pushing beyond 2 mg/kg with all the rest could have done it.
There are still a few things that do not make sense.
Why wouldn’t TLS have been the first thought that everyone had after the incident and treated accordingly? TLS is a treatable condition. Were these patients actually not treated for it, assuming they had it?
Is there a legal obligation of the investigators to make a timely report of TLS if the investigation has concluded that this is what happened? Under international law, one would expect that a duty to report such a finding is legally required. Does there non-reporting to date signify that TLS has not been ascertained. Have the investigators acknowledged to date their legal obligation under human rights laws to make this disclosure?
Hi Ovidiu,
There is no question that 3BP can cause TLS. TLS has been experienced by the Dutch boy treated with 3BP given via TACE (case report published by John Hopkins University and Frankfurt university) and actually nearly killed the boy – fortunately TLS was managed well at a hospital here in the Netherlands, so the boy could recover.
You are right, there are various ways to further improve the effectiveness of 3BP when addressing the points you’ve made and we did intensively discussed them here and on CancerCompass. What an intensive discussion we had on Cancer Compass starting back in 2014 … and J fueled that so nicely with his endless energy and enthusiasm …
Kind regards,
Daniel
D … and the melanoma patient. His entire tumor mass collapsed after that second combo with acetaminophen. If this patient had survived I do not think it would be possible that TLS would not have happened.
What if after all these years 3-BP came through for us? In all of human history no real progress has ever been made against metastatic cancer. The a priori probability that 3-BP would help was very close to zero. However, now the numbers have moved around quite a bit. Dayspring has lately been making more assertive statements about 3-BP’s effectiveness.
I promised to myself that all those people that we met along the way and who lost their loved ones that this would not be in vain; that we would build and grow and make each life lost a step towards a cure. If TLS is behind Bracht, then this will be a promise kept.
I wish that some statement will soon be made to help clarify if our speculations are in fact valid. If they are valid then 3-BP could become at the top of global headlines as a cancer treatment.
While looking for new articles on 3-BP, I found something interesting, a new compound called NEO218, which is synthesized by covalently conjugating 3-BP to perillyl alcohol (they don’t say which isomer, one of them is expensive, the other costs 50% more than 3-BP). Quoting from the article:
– severely lowered cellular ATP content below life-sustaining levels
– triggered rapid necrosis
– treatment of HCT116 cells with 3-BP resulted in prompt development of resistance, based on the emergence of MCT-1-negative cells
– this was not the case with NEO218, and highly 3-BP-resistant cells remained exquisitely sensitive to NEO218
A perillyl alcohol-conjugated analog of 3-bromopyruvate without cellular uptake dependency on monocarboxylate transporter 1 and with activity in 3-BP-resistant tumor cells.
https://www.ncbi.nlm.nih.gov/pubmed/28450161
ovidiu, yes we have discussed NEO218 here and on cancer compass. It is a very exciting development!
If 3-BP can selectively enter cancer cells using NEO218, then it would be a much much more powerful treatment. I am waiting on further news on its development.
From my current understanding NEO218 uses POH’s interaction with the plasma membrane of the cancer cell to allow it selective entry.
J, one more addition: being sure about something in oncology is challenging at this point … so we are left with making an educated guess for now.
Yes, J. Various plugins to protect from spam were down and receiving a lot of spam. Some new registered users were spam and some real.
Hi Dana
as far as i know this is quite useful against MM:
https://jhu.pure.elsevier.com/en/publications/killing-multiple-myeloma-cells-with-the-small-molecule-3-bromopyr-5
Hi Daniel
in the preparation IV of 3BP does not put you may need a PH meter;¿because the mixture with the correct quantities has a ph
suitable for intravenous infusion?.Does it occur the same in not buffer version?.thank you
D, I have been looking everywhere for the CAS number for radiolabeled 3-BP.
Might you know this?
J, I would not expect to have a CAS for a combo of substances.
D, I think I posted about this about a year ago on the compass thread. I was surfing around some of the chemical houses and I stumbled onto a radiolabeled 3-BP with a CAS number. I was fairly shocked. Was there really demand for such a chemical? My guess is Yes. From what I remember this was just plain 3-BP
with one of the carbon atoms replaced with C14. Actually now that I think about it, it occurs to me that this might have been in one of the 3-BP patents.
This has me super excited! 3-BP has been out there for 20 years and it still has not really got very far. There have been some very large responses, though others do not have such responses. What I think would help
so much is having a biomarker that could prospectively identify those patients that would have super responses.
I am not sure how the radiochemistry works, though the game plan that I have is to give something like a radiolabeled 3-BP or lactate and then do a PET/CAT (whatever) scan and see if the entire tumor mass would light up. With the liver patient and the melanoma patient, such scans would have clearly shown that they would be Super-responders. The great part about this is that with the melanoma patient he actually did not
respond at first; it was only when they added in the paracetamol. Yet, with the 3-BP scanner, the response would still be highly predictable because all you need is for the radiolabeled 3-BP to enter via MCT-1.
What is also fairly interesting about this is that it perhaps could be done under the radar. A patient could go
in for a fairly routine scan, use the existing infrastructure and possibly determine that they were super responders.
The idea here is that 3-BP would then have a very large amount of momentum to be approved under an orphan indication. The argument that has been ongoing about 3-BP could then no longer continue.
D, what do you think? I believe that finder has been thinking and working to move this idea forward quietly,
though it might be good to start a conversation about this.
Hi J,
it’s always a pleasure to read your e-mails full of energy.
The world is full of value J. There is so much valuable research, indicating so much potential for cancer patients. The difficult part is related to the fact that anything major to be done in this world requires financing. There are many dreamers like us, but is so difficult to generate a coherent move towards value if you are not an organisation with people paid to do that. Which brings us back to the current industry. So the question is J, what can we do to help advance the most valuable ideas, that the industry is not picking up due to various reasons? This is really not a rhetorical question. I really need input as I am currently thinking intensively about this.
Last time when I spoke with “finder” from CC, he was going through some challenging times. Not sure if he is still working on this line. I will check with him.
I am sure dr. ko on the other hand is working on this line. But something seems to keep her in the same place, since there is nothing happening after all these year (soon we can say tens of years).
Kind regards,
Daniel
D, the Bracht trial has started.
Prosecutors are claiming that he administered an overdose of 3-6 times of 3-BP.
What is of particular interest is that the patients were reported to have had a fatal “brain failure”.
Doesn’t this suggest TLS?
Would there not have been organic damage?
What did the autopsy results find?
The dramatic realization that might emerge from this trial is that 3-BP did, in fact, produce overwhelming
anti-tumor responses and the patients were unable to cope with the TLS. This could completely reframe
the discussion about 3-BP. 3-BP might then be seen as a cancer drug that worked too well than as a drug
that was primarily toxic.
https://www.dw.com/en/german-healer-denies-manslaughter-of-cancer-patients/a-48112127
Hi J,
Now I am back. Thanks for the info. The research team investigated the case for long time. So I trust the outcome. If they came to the conclusion that the dose administrated to the patients was 3-6 times higher, the story may change a lot. Why would you go so high? I can only imagine that was a mistake of the doctor when calculating. I can also imagine (speculation) that the administration time was reduced in a clinic compared to 2 to 2.5 hours that must be allocated to the safe dose (as they always need to fit in more patients). And since we know that both the infusion time as well as concentration plays a role in the determination of the optimal therapeutic dose, a 3-6 times higher dose may actually mean even more. Here is a patent on the impact of 3BP administration time in animals https://patents.google.com/patent/EP2114413B1
I am very surprised to hear that the dose was so high and in this conditions is difficult for me to try to guess what happened as I do not have relevant reference points in this range. Even drinking water in the range of 3-6x more than what is recommended and doing that too fast will kill you.
What I know is that when 3BP is used in the range of 2mg/kg given in about 2h, IV, it is both safe and has anti cancer effects at least in some patients. Even if taking 2x more I do not expected to be lethal if given in e.g. 3h. But beyond that, it is unknown to me.
Kind regards,
Daniel
Very very big news everyone!
3-BP intellectual property has been transferred to South Korea!
Most of the metabolic thought leaders appear to be onside.
Hello to our high intelligence Asian overlords!
Metabolic therapy has been dithered and dathered for almost a century by the West since Warburg.
It might have taken another century the way things have been inching forward:
Now? Things might actually happen!
Interesting, Dr. Ko is originally from S. Korea. I hope you are right and progress on this moves forward!
Below article seems to say combining ketogenic diet and Metformin have same effect of 3-Bromopyruvate (3BP)
https://sci-hub.yncjkj.com/10.1016/j.mehy.2011.04.001
Is it true? Is it all anti-tumor activity of 3-BP?
Please share your finding, so I would be encouraged to share & ask about my finding here, more.
Dear Mahdi,
In theory, Ketogenic diet, Metformin and 3-Bromopyruvate (3BP), they all have the same effect on cancer cells as they are all anti-cancer approaches. In practice, because they all fight cancer via a different mechanism, they will have different effects. What is important is that they all work along the same direction and not opposite, so they can be combined to enhance the anti-cancer effects.
Kind regards,
Daniel