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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Sun Dec 18, 2016 11:57 PM                   Quote | Reply

Wow, our thread has been drifting along and we have been missing out on quite a bit that has been happening in the 3-BP universe.

For example, I had been very unaware of the severity of burden on global health related to the fungal infection, C. neoformans. This infection causes substantial mortaility and morbidity among those with HIV and cancer. Existing treatments are not highly effective, nor inexpensive. 3-BP appears to have a considerable potential to help treat this condition and perhaps others as expressed in the recent 3-BP review.

https://www.ncbi.nlm.nih.gov/pubmed/?term=27983708

https://www.ncbi.nlm.nih.gov/pubmed/?term=23541578

This newly revealed potential role for 3-BP might be of considerable importance in assisting 3-BP through the clinic for cancer. Obviously a large dataset of patients treated safely and effectively with it for other rationales could be extremely helpful. It also might explain something that has puzzled me for quite a while. Why are some Chinese online chemical houses offering kilogram scale quantities of pharmaceutical grade 3-BP? I could not understand that. Perhaps the above is a plausible explanation.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Meech90 on Mon Dec 26, 2016 11:42 AM                   Quote | Reply

What do you guys think of this recent article saying that a high fat diet aids in the spread of cancer due to CD36, which is a protein identified to be important to metastasis and mediated by fatty acids: https://www.sciencedaily.com/releases/2016/12/161207132117.h  Seems to go against the conventional wisdom of the metabolic theory of cancer.

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RE: Anyone used 3bp (3-bromopyruvate)?
by dumbcritic on Mon Jan 02, 2017 12:33 PM                   Quote | Reply

Dr. Ko will give a presentation entitled: 'Understanding and Targeting Cancer Cell Energy Metabolism' at this http://metabolictherapeuticsconference.com/speakers/

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Sat Jan 21, 2017 07:12 PM                   Quote | Reply

I want the thread to know that a poster and friend of our thread, falcon, has lost his mother to cancer. He tried his best to find the treatments that would be of help, though the cancer was stronger. It sobering to remember that several others who have posted to our thread have likewise succumbed to their illness.

I so greatly wish that 2017 will bring more happiness and less sorrow in cancer therapy.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Sat Jan 21, 2017 07:14 PM                   Quote | Reply

Along that line of thought there is this:

https://www.nytimes.com/2016/12/07/health/cancer-immunothera

If the TIL approach that has been championed by the NCI for decades could finally globailze from melanoma to a wider range of cancers, then this would be a sparkle of light to celebrate.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Sat Jan 21, 2017 07:44 PM                   Quote | Reply

Pluripotency runs through the metabolic system? Question is: could you selectively differentiate cancer cells?

https://www.ncbi.nlm.nih.gov/pubmed/25738455?dopt=Abstract&a

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Sat Jan 21, 2017 11:04 PM                   Quote | Reply

I also noticed that another patent application has been filed for Mito-3-BP. This one clearly has large potential. If we can sidestep all those issues of cell entry through MCT and just drag it in an ionic tug boat, then the game certainly changes. The original article of a few years back was impressive.

I would still like to see the in vivo work. I want to be clear that toxicity is not an issue. I am not entirely sure how specific Mito-3-BP would be for cancerous cells. It would be great if this could be clarified.

Is it typical that multiple patents will be filed, when the research into a product seems dormant? There have been quite a few Mito-3-BP patents filed to date and additional publication of research has not been forthcoming.

http://www.freshpatents.com/-dt20170119ptan20170014361.php

Wonder why https://www.ncbi.nlm.nih.gov/pubmed/27983708 went with 3-BrOP over Mito-3-BP? (perhaps Mito-3-BrOP?)

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Tue Jan 24, 2017 06:43 PM                   Quote | Reply

This is starting to get quite exciting!

We have talked for a long time about minicells.

There are three ingredients needed: a therapeutic payload, minicells and a targetting mechanism. Only the last item posed particular trouble sourcing.

The bispecific antibodies needed were not readily available, some were from animal sources which could cause an immune response etc.. The below article apparently has found a way around these obstacles by using folic acid and off-the-shelve ingredients. They showed as a proof of principle that using the payload of shRNA VEGF they could achieve a response in mice.

The article noted that the presence of folic acid reduces the effectiveness of the folic acid coated minicells. This makes me wonder whether reducing folic acid levels (with anti-folates?) might increase the anti-cancer effect noted in the article.

Figure 8 from the article was somewhat misleading. The figure shows the tumor, liver cells and heart cells lit up due to the high presence of the minicells. This might indicate concerns about possible side effects to the heart and the liver. However, the authors explain that the minicells were only present in these organs due to blood flow: it was expected that little if any of the minicells would actually be retained in the tissues, most of the minicells were retained in the tumor. Are there not tests that look for chemicals that are incorporated into cells and not merely bystanders?

The research into minicells continues and they increasingly appear to offer an attractive therapeutic platform. I can hardly wait to see what results will be obtained when oncoviruses, mito-3BP, shRNA LDH, ... are tried. A wisely chosen combination should have simply near total power to control cancer.

Engeneic, the company developing these minicells, notes on their website, that they are researching chemotherapies that are 1000 more potent than those currently used. Such chemo could never be used systemically, though in minicells dosed at 1 million times lower doses, there would likely be no side effects.

(Not sure of the broader relevance of the PSMA [prostate specific membrane antigen] uptake noted in the article for prostate cancer.)

https://www.ncbi.nlm.nih.gov/pubmed/27378204

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Tue Jan 24, 2017 07:22 PM                   Quote | Reply

Hmm, this goes back to ernemef's article on the radioactive PMSA treatment.

http://atlasofscience.org/a-novel-radionuclide-treatment/

No, side effects were noted in normal prostate cells.

Would have liked to see in the folate minicell article if there might have been any prostate problems. Normal prostate cells express PMSA, prostate cancer cells express quite a bit more. Wonder if this might limit the application of folate minicells cells as a cancer treatment.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Wed Jan 25, 2017 12:07 AM                   Quote | Reply

Very interesting!

Here's a preprint of an article that focuses in on the GSH 3-BP connection. The point noted earlier on the thread that 3-BP has a nearly singularly unique property among chemotherapeutics in that it can be recalled by applying GSH/NAC is highlighted in the article. This feature if it had been fully appreciated at Bracht might have changed what happened there. GSH/NAC should become a standard on the shelf emergency protocol for 3-BP treatment crises.

The article below is also of interest in that it goes on to mention high dose paracetamol with NAC rescue. I thought that there was an error when the article talked of >10g/m2 that seemed much too much paracetamol (perhaps even toxically so).

However, https://www.ncbi.nlm.nih.gov/pubmed/12690304 was a phase 1 trial using an MTD of 15g/m2. It is surprising to me that this has not been noted before. A combination of 3-BP along with high dose paracetamol with NAC rescue might yield more responses, though this would need to be done carefully preferably within a highly professional medical context.

This study found a counterintuitive decrease in effectiveness with high dose paracetamol treatment. https://www.ncbi.nlm.nih.gov/pubmed/17526808  &nbs

Would really like to see a minicell treatment using paracetamol or shGSH. In my view it is becoming increasingly clear that using systemic dosing when minicells are available is primitive.

http://ac.els-cdn.com/S0306987716303462/1-s2.0-S030698771630

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Wed Jan 25, 2017 12:23 AM                   Quote | Reply

Brings me back to this one.

Wonder why the preprint didn't mention Curcumin?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567432/

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Wed Jan 25, 2017 10:42 PM                   Quote | Reply

Dayspring is once again an official named 3-Bromopyruvate clinic.

http://www.dayspringcancerclinic.com/

I think in light of what happened at Bracht the thread should consider a treatment protocol that could address some of the safety issues that are inherent to the use of 3-BP.

Some of the ideas I have thought of include:

- on-site GSH if treatment were to go wrong (though not necessarily requiring that the clinic itself would administer it)

- spectrophotometer to confirm dosing for each batch

- only single patient dosing if a new batch or formulation is used with a 1 hour window to the next dosing

- no single employee clinics. If something were to go wrong, then a team would be needed to help

- more transparency with actual clinical results would also be very welcome

The big concern is that even after a serious incident often there are no changes that would truly improve safety.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Wed Jan 25, 2017 10:59 PM                   Quote | Reply

I am sure that D was all over this one, though I only noticed now that metformin combined with 2DG seems to be fairly effective. The idea was that 2DG for blocking glycolysis and metformin for OXPHOS. An article noted that using only 2DG or 3-BP might be ineffective because only one energy pathway would be blocked.

https://www.ncbi.nlm.nih.gov/pubmed/21992792

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RE: Anyone used 3bp (3-bromopyruvate)?
by dumbcritic on Mon Jan 30, 2017 06:26 PM                   Quote | Reply

“We will start with a baseline trial testing the arginine-depleting drug against sarcomas with this defect, and then we can begin layering additional drugs on top of that therapy,” Van Tine said. “Unlike breast cancer, for example, sarcomas currently have no targeted therapies. If this strategy is effective, it could transform the treatment of 90 percent of sarcoma tumors.”

https://medicine.wustl.edu/news/study-unveils-new-way-starve

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RE: Anyone used 3bp (3-bromopyruvate)?
by dumbcritic on Mon Jan 30, 2017 11:51 PM                   Quote | Reply

Look to improve in-situ tumor vaccination

In preclinical studies although cryoablated mice remain tumor free, only 20-50% survive a rechallenge with melanoma cells, indicating that a minority developed efficient immunologic memory against the tumor. These findings emphasized the need to boost antitumor immunity by combining tumor-destructive treatment with adjuvant immunotherapy. In further studies with the administration of the toll-like receptor (TLR) 9 agonist, CpG oligodeoxynucleotides, immediately after the ablation elevates the numbers of cytotoxic t lymphocytes in the lymph nodes and promoted survival rates upon rechallenge to 90-100% http://cancerres.aacrjournals.org/content/66/14/7285.long http://journals.plos.org/plosone/article?id=10.1371/journal. http://cancerres.aacrjournals.org/content/68/13/5390.long

Individual TLR agonists can significantly improve the host's immune response to small tumors. But to be effective against large established tumors, a number of TLR agonist combinations seem to be needed. Based on preliminary studies, the combination of TLRs 7/8 with a TLR 9 can eliminate most large established tumors https://jitc.biomedcentral.com/articles/10.1186/2051-1426-2- To further improve upon these effects then you could also add a STING agonist as well http://www.cell.com/cell-reports/fulltext/S2211-1247(15)00432-5 Some previous studies shows that TLR 9 and STING synergistic effect http://onlinelibrary.wiley.com/doi/10.1002/eji.201445132/ful

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RE: Anyone used 3bp (3-bromopyruvate)?
by dumbcritic on Tue Jan 31, 2017 12:09 AM                   Quote | Reply

'' Seems to go against the conventional wisdom of the metabolic theory of cancer.'' It's the chicken or the egg argument. Whether it's the metabolic abnormalities that cause the mutations observed in cancer cells or whether it's the mutations that produce the metabolic abnormalities. It's possible as certain cancer cells evolve they can utilize certain lipids. So this might call into question the ketogenic diet for patients.

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RE: Anyone used 3bp (3-bromopyruvate)?
by chris1023 on Fri Feb 03, 2017 01:04 PM                   Quote | Reply

I also think they should post clinical findings in all cases. Not just the ones that respond.

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RE: Anyone used 3bp (3-bromopyruvate)?
by dumbcritic on Sat Feb 11, 2017 01:30 AM                   Quote | Reply

Legally as of Jan of this year, it should be much tougher for a company to simply disappear with regards to posting results of finished trials https://www.statnews.com/2016/09/16/clinical-trials-reportin

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Tue Feb 14, 2017 09:10 PM                   Quote | Reply

Happy Valentine's Day  everyone!

D has set such a great tone of love and compassion on our thread that it seems such an appropriate date to post. His research efforts and his personal devotion as a caregiver have set an example to all of a love filled life.

I have been reading some very exciting metabolic cancer research and have been carefully contemplating the events of the last year. I have concluded that the fundamental message of our thread of propounding the virtues of cancer metabolics is as valid as ever. There is so much unexplored potential on this horizon it is truly bewildering that it has not been examined in more detail.

One group that is exploring this landscape is Dayspring. They are now reporting another patient. This patient is dated Feb 2017 and has stage IV bile duct cancer. I am unsure whether some of these patients would even be treated elsewhere. It is highly impressive that Dayspring has consistently reported patients that from the reports provided seem almost unhelpable. (Of course, they are selecting which patients are reported.) We would really love to hear from patients who might have been treated at Dayspring with 3-BP. Perhaps  you read our thread and this helped you decide, please post we would all really love to hear from you.

I also impressed by the integrity Dayspring has shown by staying with 3-BP treatment when it would be so much easier to move into another treatment. Dayspring probably has one of the best understandings of anyone in the world of the clinical effectiveness of 3-BP and it is reassuring to see that their clinical experience supports continued use.

Feel the love!

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Tue Feb 14, 2017 11:43 PM                   Quote | Reply

This one has several statements that really jumped off the page for me.

"It is to be noted that many studies have shown that cells with aerobic glycolysis have a clear proliferative advantage over cells that use mitochondrial oxidative phosphorylation "

To what extent might the strategy of cancer be to simply starve normal cells of glucose? It is true that glycolysis is not efficient versus OXPHOS, though with cancer consuming up to 200 the glucose of other cells perhaps it is simply a strategy of gobbling up all the food in sight perhaps forcing neighbouring cells to evolve in the same direction. Not sure if they considered this idea within the concept of their theory.

They developed a theory that Warburg's effect might be the driver of cancer. With one metabolic driver as :"the teleological reason for recruiting of α-ketoglutarate as a cosubstrate to regulate the activity of HIF1"

"metabolic plasticity is a built-in feature that allows even normal cells to acquire aerobic glycolysis under many physiological conditions."

They are pushing a Warburg plus effect "the initial event in sporadic cancer is the fortuitous shift to aerobic glycolysis, which then provides a unique environment for cells to proliferate rapidly and evolve in a cooperative fashion."

Love to see some lab research that could mimic cancer in the lab using this approach.

"in principle, Warburg effect, once initiated, can substitute for a mutation"

"indicates that fluctuating levels of α-ketoglutarate can drive a cell to a new phenotype purely due to noise in the system."

"a fortuitous metabolic shift followed by epigenetic modification and genetic alterations seems to be the sequence of events that occurs in cases of sporadic cancers. "

"the role of hexokinase II (HXKII) and glucose metabolism in aerobic glycolysis is highlighted by the observation that H-19 hepatoma cells produce more lactate when glucose is used as the carbon source as compared to galactose. Consistent with this, HXII protein, an apoptotic suppressor, is associated with mitochondrial fraction only when glucose but not galactose was used as the carbon source,

INDICATING that apoptotic suppression is specific to glucose metabolism "

That one really leapt off the page for me. Apoptotic suppression is specific to glucose versus galactose metabolism? I would need to read up on that one. Could apoptosis be encouraged by simply switching to galactose?

"can also explain the phenomenon of reversion of cancer cells to normal cells " Very startling! Cancer cells can revert back to normal cells?

"more than 90% of ovarian cancer is due to ovulation-induced wound repair"

The far reaching position of the article:

"because of noise, a stable glycolytic phenotype can be manifested and propagated during cell division in normal cells, independent of genetic or epigenetic event, provides a conceptually new avenue that would radically alter the way we think about cancer. "

Cancer that could be independent of genetics, the thread has taken a weaker take on this by often suggesting that genetics is downstream of the driving process. This article is putting forward the seemingly radical proposition that cancer or a precancer state could exist in normal cells due to a stable glycolysis created from noise in the biological system.

"a cancerous state as one of the aberrant developmental options available to a normal cell"

https://www.ncbi.nlm.nih.gov/pubmed/22704333

A very thought provoking article.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Wed Feb 15, 2017 07:42 PM                   Quote | Reply

critic, the article that I just posted resolves the chicken and egg question in a fairly unique way, there is no chicken and egg! The article is proposing that a cancer phenotype could spontaneously emerge simply noise in the biological system. They suggest that this could push cells into a stable hyperglycolysis state without the need for genetic or epigenetic drivers. This would seem to be a new and innovative departure from the current accepted wisdom.

Yes, chris I think greater transparency about results from 3-BP treating clinics should be forthcoming. If clinical trials are not to begin in the near time horizon, I am unclear why such disclosures are not a legal requirement.

We have learned from the Bracht investigation that a substantial number of patients were treated with 3-BP there (perhaps more than 100) and apparently few if any actually saw a benefit from their treatment. I am not sure why this has not been more fully reported and investigated by the media and investigators. Regulators allowed this and other clinics to continue treating patients, while tacitly permitting efficacy claims on the clinic websites. At the same time this treatment did not help the patients.

3-BP is a maturing treatment and fuller disclosure of clinical activity should be required. It would be very helpful if the Right to Try activists were to advocate for such disclosures. Many people have succombed to illnesses all the while seeking treatments from clinics who would reasonably have been expected to know such treatment would be futile. Where is the rage?

I was also thinking that the idea of an initial treatment with sub-therapeutic 3-BP dosing should also be encouraged. 3-BP is a fairly unique treatment in that it can show very rapid effectiveness. Many people including some on thread likely would be willing to pay for 3-BP if it were known to be effective before a substantial bill was due for a full round of treatment. 3-BP clinics that offered such a treatment plan would be showing good that they believed in their product and were focused on the best interests of their patients. We should also be advancing this concept which has now been discussed on thread of years.

I would really love to hear from the stage IV bile duct cancer. We have been through a lot of grief with what happened at the Bracht clinic, it would be so uplifting to hear some success stories. I am sure you must be familiar with our thread, please post!

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RE: Anyone used 3bp (3-bromopyruvate)?
by Meech90 on Wed Feb 15, 2017 07:48 PM                   Quote | Reply

On the note of glycolysis and apoptosis suppression: it can be logically assumed that in cells in cells with mutated or inactivated p53 (large amount of cancers, over 50%), that mdm2 is activated since activation of mdm2 suppresses activation of p53. mTOR is an activator of mdm2. mTOR also activated HIF1-a. p53 is a tumour suppressor protein. During the cell cycle, if there is cell damage, p53 halts cell cycle progression in the G1-S phase and it attempts to repair the damage. If damage is successfully repaired, it allows the cell cycle to continue as normal, but if the cell cannot be repaired, it initiates apoptosis. You can see where the mutation or disabling of this gene could lead to infinite replication among cancer cells. This is all part of the PI3K-Akt-mTOR pathway, and this pathway is enabled by either PTEN being knocked out or via a mutation called PIK3CA. I'm not sure how many cancers exhibit mutations in the PI3K-Akt-mTOR pathway but it certainly is not all of them. This could be one partial explanation of why glycolysis can lead to suppression of apoptosis. mTOR can encourage both glycolysis through activation of HIF-1a as well as suppression of apoptosis by indirectly shutting off p53. This is all hypothesis by me by the way, so take it with a grain of salt haha.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Meech90 on Wed Feb 15, 2017 07:49 PM                   Quote | Reply

Sorry about the lack of formatting. I typed it on mobile and I guess the line spacing wasn't recognized.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Wed Feb 15, 2017 08:22 PM                   Quote | Reply

Meech, thank you for posting.

Yes, cancer appears to have strategically switched to glycolysis partly to prevent the apoptosis inititation mechanism of mitochondria. In recent research it was found that mitochondria can circulate in the blood stream. Would be very interesting to know whether injecting functional mitochondria into cancer patients might show efficacy.

I was also glad to read more about HIF-1. As you mentioned and also in the recent article I cited there are important feedback loops with HIF-1.

Starting from the basic metabolic machinery layers of feedbacks loops accumulate. Considering that life most likely began as not much more than glycolysis and DNA greatly clarifies what is truly the essential essence of cancer.

Don't worry about formatting, there is no edit function here so it is best to just let typos happen.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Wed Feb 15, 2017 08:31 PM                   Quote | Reply

Go Oz Go!

Wow!

"In less than 20 minutes the tumour had gone purple then black"

https://www.qbiotics.com/index.php/public-relations

This is only for intratumoral and is only in phase 1 though it is impressive.

D, how might they be able to convert this to a systemic drug?

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Wed Feb 15, 2017 08:48 PM                   Quote | Reply

I elect ernemef, to go up to the mangrove swamps of Northern Queensland and locate some seeds from the Blushwood tree. Erne, mind the crocs up there, there's some mighty big hungry crocs in those swamps.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Wed Feb 15, 2017 09:56 PM                   Quote | Reply

Click on the 3D model Jmol interactive image link to see it. https://en.wikipedia.org/wiki/EBC-46

Molecular Formula C30H42O10.

Appears to have truly profound anti-cancer properties limited to intratumoral injection.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182759/

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RE: Anyone used 3bp (3-bromopyruvate)?
by dumbcritic on Thu Feb 16, 2017 03:09 AM                   Quote | Reply

G100 is administered intratumorally. The first group had three patients in it and all had locoregional stage IIIB merkel cell carcinoma. The drug was injected on days 0 and 7 followed by surgery on day 28. Two of the three are still recurrence free at months 19 and 23 and the other patient had a pathologic complete response. In the second group then seven patients had stage IV. This was injected on days 0, 7 and 21. It was followed by optional treatment cycles in months 2-4. If patients had this then on day 0 they got a single fraction of 8 Gy of radiotherapy to one tumour followed by injections on days 1-3, 7, 14 and 35. Two of the seven patients have had reductions of their tumour burden by 30% or more and responses are ongoing (17 and 18 months). Most of the side-effects were mild http://www.immunedesign.com/wp-content/uploads/2016/06/MCC-A This can be combined with other IT treatments like IL12 http://www.immunedesign.com/wp-content/uploads/2016/04/2016- SD-101 is another agent that is administered intratumorally. In this trial they recruited 28 patients with biopsy-confirmed, untreated, low-grade B-cell lymphoma (follicular, marginal or chronic lymphocytic leukemia/small lymphocytic lymphoma) with lymph node involvement (appropriate candidates for watch and wait). Most of them had stage III or IV follicular lymphoma. On days 0 and 1 they all got 2 Gy of radiotherapy followed by injections on days 1, 8, 15, 22 and 29. Around 70-75% had reductions in their tumour burden. For most patients the responce has been durable ranging up to almost day 600. Three patients had a partial response (PR) and1 had a complete response (CR) as measured by Cheson criteria. http://files.shareholder.com/downloads/DVAX/2548598851x0x921

Rose bengal (PV-10) has been used IT for HCC and liver mets http://provectusbio.com/media/docs/publications/CIO%202017%2

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RE: Anyone used 3bp (3-bromopyruvate)?
by ernemef on Thu Feb 16, 2017 08:15 AM                   Quote | Reply

Thanks J for your faith in my ability to undertake such an honorable task but regretfully I'm afraid I must decline. I am still recovering from a recent trip to Lisbon to have a PAE (prostate artery embolization) performed by Professor Pisco on my prostate cancer. He has done 29 so far. I would have been number 30 but although all external tests were propitious, once they were inside unfortunately my prostate artery was found to be too narrow for their catheter and so the operation failed much to my regret, and I have had to return to Australia much lighter in the hip pocket.

As well as the embolization I would have received a mini dose of docetaxel directly into the prostate at the same time.

I think we are going to see a lot more prostate PAEs done in the near future.

Obviously the procedure could be adapted to 3BP once it is proved safe and maybe even the mangrove swamp berry extract as well.

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RE: Anyone used 3bp (3-bromopyruvate)?
by peggyznd on Thu Feb 16, 2017 06:12 PM                   Quote | Reply

The blue scorpion venom is not tested in any clinical trials, and is not apparently of any interest to others than those who sell it. Must say that this is not likely to give benefit, but wish it were possible to kill tumors so easily. If it were the case, some pharmaceutical company or academic center would be breeding these scorpions and creating a meaningful product.

There are often 'active' ingredients which work in a petri dish or seem to help an individual or two, but without real studies, this type of reporting is quite unreliable. Sorry to have to remind us.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Feb 16, 2017 07:59 PM                   Quote | Reply

Thank you very much for posting, ernemef!

Seems like everyone has more interesting things to write than I do. I am more of a talker than a listener, though it is often instructive to pay careful attention to what others say when you need to inhale.

Prostate TACE? Is this a new one? D suggested that TACE could be done nearly anywhere in the human body. I wonder if the conceptual idea of controlling cancer and converting it to a truly chronic life long illness by simply TACEing all the major organs might be valid. Patients might wind up with large cancer burdens while at the same maintaining good overal organ function.

The Blushwood tree treatment seems ridiculously powerful as an intratumoral injection.

"Usually when you treat a tumor it takes several weeks for it to resolve, but this is very, very rapid. There’s a purpling of the area, of the tumor itself, and you see that within five minutes and you come back the next day and the tumor’s black and you come back a few days later and the tumor’s fallen off.”

http://naturalsociety.com/blushwood-berries-kill-cancer-75-c

Wow! These were the results that they found with almost 200 animal patients. The two phase 1 clinical trials are finding similar results in people. Would really love to see whether this might be transitioned to a systemic treatment.

"If this goes well, there is potential for treating internal tumours where injection can be guided through imaging processes."

http://www.ucansurvive.org/editor/assets/qimr_articles/natur

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Feb 16, 2017 08:33 PM                   Quote | Reply

Anyone notice that someone known to our thread has an article published? Well done.

CELLULAR ACIDIFICATION AS A NEW APPROACH TO CANCER TREATMENT AND TO THE UNDERSTANDING AND THERAPEUTICS OF NEURODEGENERATIVE DISEASES

The article discusses the role of the acid/base balance within and outside of cancer cells as a regulator of cancer survival.

I was very impressed by the article I recently cited that tried to focus on the emergence of hyperglycolysis as a cell state that could be stably maintained even without genetic changes merely due to cell noise. It is hard to know for sure, though the above article appears to provide a solid framework to consider that the acid base relationship might be an equally fundamental driver of cancer cells possibly in a more intuitive manner (while this is probably intereconnected) than even hyperglycolysis.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Feb 16, 2017 08:47 PM                   Quote | Reply

Would have liked to see the article mention ACCA.

"Highly malignant tumors rely heavily on aerobic glycolysis (metabolism of glucose to lactic acid even under ample tissue oxygen; Warburg Effect) and thus need to efflux lactic acid via MCTs to the tumor micro-environment to maintain a robust glycolytic flux and to prevent the tumor from being "pickled to death ... a small-molecule inhibitor alpha-cyano-4-hydroxycinnamic acid (ACCA; CHC) to show that inhibiting lactic acid efflux is a very effective therapeutic strategy against highly glycolytic malignant tumors" wiki Monocarboxylate transporter

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RE: Anyone used 3bp (3-bromopyruvate)?
by zmkdr on Thu Feb 16, 2017 09:58 PM                   Quote | Reply

I tried blue scorpion venom during the month of January with no effect. I actually progressed.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Fri Feb 17, 2017 06:28 PM                   Quote | Reply

Thank you very much for posting, ernemef!

Seems like everyone has more interesting things to write than I do. I am more of a talker than a listener, though it is often instructive to pay careful attention to what others say when you need to inhale.

Wow, prostate TACE! Is this a new one?

D suggested that TACE could be done nearly anywhere in the human body. I wonder if the conceptual idea of controlling cancer and converting it to a truly chronic life long illness by simply TACEing all the major organs might be valid. Patients might wind up with large cancer burdens while at the same maintaining good overal organ function.

The Blushwood tree treatment seems ridiculously powerful as an intratumoral injection.

"Usually when you treat a tumor it takes several weeks for it to resolve, but this is very, very rapid. There’s a purpling of the area, of the tumor itself, and you see that within five minutes and you come back the next day and the tumor’s black and you come back a few days later and the tumor’s fallen off.”

These were the results that they found with almost 200 animal patients. The two phase 1 clinical trials are finding similar results in a small number of people. Would really love to see whether this might be transitioned to a systemic treatment.

"If this goes well, there is potential for treating internal tumours where injection can be guided through imaging processes."

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Fri Feb 17, 2017 09:14 PM                   Quote | Reply

It has only now occurred to me that the two patients reports for 3-BP that we have endlessly referenced on thread did not report on why these patients responded so profoundly to treatment.

Hopefully any future articles on 3-BP published patients will have detailed reasons for why one patient might have responded, while another patient did not respond. In this genomic age it would not be unreasonable to expect full genome sequencing of the patient's somatic and cancer cells. Having such details would be of great benefit as this would give prospective patients even greater insight into their liklikhood of responding and inspire them to seek 3-BP if it were felt to have particular potential for a particular patient. It might also allow for manipulaiton of a patient's biology to increase the chance of success.

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RE: Anyone used 3bp (3-bromopyruvate)?
by mikeadams on Fri Feb 17, 2017 10:03 PM                   Quote | Reply

From this https://sciencebasedmedicine.org/3-bromopyruvate-the-latest-

''As I pointed out with DCA, the widespread use of 3-BP leading to complications such as these deaths of patients under Ross’ care could endanger its clinical trials and approval. After all, what companies or venture capital firms would want to partner to fund studies of 3-BP after this news? If 3-BP is really an effective anticancer treatment in humans, this recklessness on the part of alternative cancer clinics could deny cancer patients a truly effective drug by tainting it with their association.''

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Fri Feb 17, 2017 11:35 PM                   Quote | Reply

mike, thank you for posting.

Welcome aboard!

Always great to have someone new to the discussion with a fresh outlook. Posters do not have to agree with the main narrative of the thread here, though those with dissenting opinion need to point to evidence instead of rhetoric to gain the confidence of the thread.

Yes, the sciencebasedmedicine does have a strongly articulated stance favoring the scientific method.

However, for a site that is strongly orientated to factual reporting there are some statements made in the above url needing rebuttal.

For example, as we have discussed on several occasions on this thread the treatment effect seen in the melanoma patient cited on sbm was not "minimal". Combination of 3-BP with paracetamol produced a profound anti-effect after two combo treatments. The patient's LDH went from 4500 to 12. I simply do not see how this can be dismissed. Such a dramatic decline constitutes a metabolic cure. See pubmed: 24636230. Notice on the far right of Figure 3 that LDH levels approach 0 after the 2nd combo treatment.

It is also unclear to me why the sbm site goes on at length describing how truly hopeless the liver patient's plight was. There did not seem to be any available options, the patient was in an acute terminal stage of cancer and 3-BP consistently had profound anti-cancer effects. We have also noted on several occasions on thread that the demise of the patient could with some justification be understood to have resulted from focusing too heavily on his cancer and not enough on his liver function. The sbm goes on and on with these long extended quotes: all of which boil down to the patient was profoundly sick; 3-BP had a profound anti-cancer effect. Do they think that we do not know how to read?

Also the comments from the url are no longer avaiable. One interesting comment that was made was that sbm vehemently denied that the article was suggesting that 3-BP was quack medicine, instead that it was medicine treated by a quack. There is a large distinction and they wanted it to be clearly known that even though quack medicine and 3-BP were often used in the same sentence that it should in no way imply that they believe that 3-Bp is quack medicine. OK?

Given the ongoing depth of research that continues to accumulate behind 3-BP, it becomes ever less credible to suggest that 3-BP is in fact quack medicine.

sbm also describes Dayspring as a quack clinic. At the same time Dayspring has continued to post 3-BP success stories with patients that in fairness would seem to truly have no available options. Also of note is that MD Anderson, widely considered the world's premiere Cancer Center (therefore, not a quack clinic) has developed a slightly modified version of 3-BP called 3-BrOP and has reported some equally impressive preclinical results with it. Not much has been heard of it though of late. Quote | Reply

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Sat Feb 18, 2017 10:38 PM                   Quote | Reply

Very exciting!

I have spent the day firming up my understanding on the mechanism behind DCA. D's site has a great review from earlier in the year and his article motivated me to learn more.

The translational research continues to role out for DCA. The role of GSTZ1 genotypes, the importance of upregulating SLC5A8, a new formulation that is emerging (diisopropylamine dichloroacetate), and also a chitosan-dichloroacetate (CSDC) formulation are all helping to move DCA forward even more than 10 years since its debut. A similar path of incremental development might also emerge for 3-BP.

One question: How might upregulating Pyruvate dehydrogenase phosphatase (PDCP1) fit into DCA treatment?

DCA turns Pyruvate dehydrogenase (PDH) back on by turning Pyruvate dehydrogenase kinase (PDK) off. With PDH on, pyruvate can continue along the normal metabolic path to acetyl-CoA and onward to the TCA cycle and then OXPHOS.

Pyruvate dehydrogenase phosphatase (PDCP1) also reverses the phosphorylation of PDK. DCA and PDCP1 both turn down PDK activity, so perhaps it might be worthwhile to increase PDPC1.

Also wonder about the newly discovered mitochondrial pyruvate carriers. Might increasing MPC activity in order to move pyruvate into the mitochondria be helpful to fuel up OXPHOS? PMID:27911865 Appears that cancer has used this for metabolic reprogramming. Felt really great to develop a firmer understanding of DCA. today. Very encouraging to see all these products moving closer and closer to the goal line.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Sat Feb 18, 2017 10:49 PM                   Quote | Reply

I just have to post this one.

Anyone care to guess how many journal articles were published in 2000 came back as hits for "Warburg effect" AND (cancer or tumor)?

0!

We might now all take the "Warburg effect" as a near central truth about cancer, though this is only a recent trend. It has only been in the last 10 years that there has been an enormous interest develop in it. Probably in fair measure as a result of DCA and then 3-BP.

Difficult to understand that the scientific community would be so fixated on the latest fads and nearly entirely neglect what our thread understands as an integral component of cancer.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4784299/

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Sun Feb 19, 2017 01:19 PM                   Quote | Reply

Speechless!

PMC4440852

Phase 1 clinical trial started last March .

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RE: Anyone used 3bp (3-bromopyruvate)?
by peggyznd on Sun Feb 19, 2017 03:51 PM                   Quote | Reply

Where is the reference to the Phase I clinical trial? I can't findit, but do get led to a series of studies.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Sun Feb 19, 2017 04:27 PM                   Quote | Reply Very startling! In the article the tumor volumes went to zero and stayed there. I never remember seeing that before.

Active ingredient appears to be synthetic cyclic dinucleotide (CDN) derivatives. Cyclic dinucleotides are basically two nucleotides attached through the phosphate group.

One can only hope that we will soon enter an era in which home remedies for serious medical conditions can be discontinued. Go pharma, go!

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Sun Feb 19, 2017 11:23 PM                   Quote | Reply

ernemef, just reading about this one and I was thinking of you. Heard of Bipolar Androgen Therapy? Aften the CDNs everything seems like a home remedy, though perhaps you might be interested.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Wed Feb 22, 2017 01:51 PM                   Quote | Reply

2DG and fenofibrates.

https://www.sciencedaily.com/releases/2016/05/160518141255.h

There is a fair amount of excitement on D's site over citrate. It is truly amazing how many points along the metabolic pathway are available for manipulation. It would be well advised for all of us to carefully reflect on how energy is used by cells and how these steps are regulated. The answer seems to be right there.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Wed Feb 22, 2017 10:01 PM                   Quote | Reply

Very exciting everyone. There is a real ah ha type moment out there putting together citrate and the other anti-metabolics into an integrated approach treatment strategy.

I think this has been mentioned on the thread before, though I have only recently looked at this one more carefully. Calithera is working on a glutaminase product that can hugely reduce its activty (pdf below seems to suggest 100%?). Combining a pharmaceutical such as that with other metabolic interventions could significantly increase effectiveness. Glutamine as several important functions that are of interest to our thread.

http://www.calithera.com/wp-content/uploads/2016/11/Phase-1-

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RE: Anyone used 3bp (3-bromopyruvate)?
by kbmac on Thu Feb 23, 2017 01:33 AM                   Quote | Reply

Please send  me the link to chinese source of 3BP. Thank you

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RE: Anyone used 3bp (3-bromopyruvate)?
by kbmac on Thu Feb 23, 2017 01:36 AM                   Quote | Reply

Please send me the chinese contact to purchse 3BP. Thank you.

Karen

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RE: Anyone used 3bp (3-bromopyruvate)?
by Meech90 on Thu Feb 23, 2017 06:08 PM                   Quote | Reply

The main exciting news for me here is that safe dosages of glutamine inhibitors are being tested. I feel like a much better strategy can be thought of than solely the one that the trial was testing.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Meech90 on Thu Feb 23, 2017 06:12 PM                   Quote | Reply

By blocking the PI3K/mTOR/Akt pathway, I would assume that you're conditioning the cells to be more sensitive to apoptosis through eliminating a pathway that tends to block p53, and blocking an escape mechanism from this pathway seems to doubly do that. I would think adding a cytotoxic chemotherapy to this protocol would yield some promising results. Especially since the majority of patients experienced tumour progression arrest, indicating that the combination therapy was sufficient to block the tumour's metastatic and proliferative properties but was largely unsuccessful at inducing apoptosis.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Feb 23, 2017 09:39 PM                   Quote | Reply

Meech, you are so correct. Often with cancer trials they are testing a drug in a way that could never be shown effectiveness. Perhaps the rule that drugs need to show efficacy as single agents should be relaxed.

I was not clear about what I meant about the ah ha. This was meant to express my appreciation of all the other metabolic targets out there.

I have been very focused on 3-BP and have not been as aware of the others as I should have been. There is a whole list of them. 3-BP, DCA, ketogenic diet, sodium fluoride (applicable to humans?), citrate, alpha lipoic acid and hyroxycitrate, and on and on. D's polypharmacy approach makes so much sense. Others should be aware that rotating through them until finding something that creates a response is a fairly good strategy.

Wonder when a clinical trial might start up based on this idea. Instead of a trial with one or two agents, why not try a basket full? The end point would be best response. One of the great parts of many metabolic approaches is that knowing whether a response will or will not occur often can be discovered very quickly. Often people will stick with something even when it has not been shown to be effective.

I have been reading through quite a few articles of late and these caught my eye.

Passenger Deletions Generate Therapeutic Vulnerabilities in Cancer

The example given in the article is ENO1 and ENO2 from  glycolysis. Article notes that often a cancer gene can be mutated and along with it a nearby gene such as ENO1. This would not cause a problem for the cancer because there is a backup copy with ENO2. Together they are essential genes, though when one is mutated the cell can carry on. Now if the backup copy is also inactivated by a pharmaceutical, the cancer cell cannot carry on, while the normal cells can lose ENO2 activity and still have a backup with ENO1.

That's pretty neat thinking.

Identification and characterization of essential genes in the human genome

This article found that there are about 2000 essential genes.

Might be worth doing a moon shot, finding all the genes that have redundancy and finding a blocker for all of them. Cancer cells that had one of these missing would be unable to survive if the other one were blocked. This would be all the more true of later stage cancers that had a greater tumor burden. It would also be true of e.g. melanoma which is known to have a very high mutation burden compared to other types.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Fri Feb 24, 2017 09:18 PM                   Quote | Reply

Something has put into perspective what we have been trying to achieve on our thread over the last four thousand, 2 hundred and fifty posts.

The lastest pubmed article that is pulled up by a search for 3-BP is PMID:27938509. This article begins by noting that liver cancer (HCC) is a leading cause of cancer mortaility worldwide. PMID:25651787 calls liver cancer the number 2 global cause of cancer mortailty.

Most of these patients are not diagnosed until a late stage of the illness. At which point there is only one FDA approved option: sorafenib. Sorafenib was approved in 2008. The partial response rate is 2%. Sorafenib was found to increase median survival by 2.8 months. The article then described what happened when they combined sorafenib with antiglycolytics including 3-BP in cell culture. They tried 3-BP, it was not effective in combo.They tried Gossypol, it was not effecitve.They  tried lmatinib, it was not effective.They  tried Lonidamine, it was not effective. They tried 2DG, it was effective. "This profound decrease in cellular-ATP level was observed in both parental and sorafenib resistant Huh7 cells." The authors talk about moving this one further along in the research pipe. This article highlights for me the substantial potential of the metabolic approach to help many people who are coping with metastatic illness. This is all the more true when you compare the Global Cancer Statistics article noted above to the version of the article quoted in the above described research from the year before. As can be seen by such a comparison we are now in the midst of a global cancer pandemic. It is urgently necessary to try innovations such as what is reported with the anti-glycolytic combination. Otherwise the numbers are going to continue to increase exponentially. (It is somewhat surprising though that this research is being reported 10 years after the approval of sorafenib.) Quote | Reply

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RE: Anyone used 3bp (3-bromopyruvate)?
by ernemef on Sat Feb 25, 2017 12:10 AM                   Quote | Reply

Jcancom, yes I have heard of it but was switched off from reading up on it by the words Androgen Therapy which I am averse to. Now that I have had a proper look at it I am certainly interested though it is still very experimental and far off clinically I'm afraid, but a step in the right direction.

Here are a few comments: A New Prostate Cancers Treatment Strategy – Part 3 of 3

Bipolar androgen therapy is probably not for “men who have not yet had any treatment for prostate cancer”. Moreover, the long-term effects or dangers of the therapy aren’t yet known. Only longer, larger trials will mitigate uncover any risks associated with the treatment. And one expert worries that alternating testosterone levels could actually shorten men’s lives. “A cancer cubicle could escape and grow, as happened in breast cancer when this method was tried with estrogen, causing early death,” said Dr Anthony D’Amico, chief of radiation oncology at Brigham and Women’s Hospital in Boston. D’Amico agreed with the think over authors that bipolar androgen therapy is not ready to be used in clinical practice and doctors should wait for the results of ongoing trials before gift it to men.

The promising developments always seem to be just over the horizon. Maybe however the time is nigh for banishing the bogie of testosterone in prostate cancer. A few studies have shown that patients with high levels of testosterone survive longer than those with low levels, though I can't recall where I read this. Professor Morgentaler (Boston) has for many years been thinking along these lines..

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RE: Anyone used 3bp (3-bromopyruvate)?
by dumbcritic on Sat Feb 25, 2017 06:12 AM                   Quote | Reply

A new paper: Press-pulse: a novel therapeutic strategy for the metabolic management of cancer http://nutritionandmetabolism.biomedcentral.com/articles/10.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Sat Feb 25, 2017 02:20 PM                   Quote | Reply

Good one critic! The article was very well written and pulled together many of the ideas that have been of long term interest of the thread.

I think it might have been helpful for the article to have included the idea of cycling through various anti-glycolytics. I do not think the article was explicit in this regard, though mentioning several in the class (including 3-BP) might be understood to imply this.

Something that has perhaps not been talked about enough in the cancer as a metabolic illness conversation is mitochondrial replacement (mitophagy). The article went into depth discussing the deficiencies in mitochondrial function related to cancer. A simple minded rebuttal would be if cancer is caused by defective mitochondria, then why not make more mitochondria (hopefully ones that are not defective). See url below starting at post #127.

As a reply to post #127:

"But since mitochondria are already shut down, I don't see the point of an anti-mitochondrial in general, especially as that might damage the entire organism."

Doing a mitochondrial reset and eliminating "zombie mitchondria" might allow for mitogenesis to create functional mitochondria. Functional mitochondria could then undergo apoptosis. I am not sure, though, whether functional mitochondria would emerge from this process.

It is interesting to note that PQQ, niacin and others mentioned in the Longecity thread do have anti-cancer activity. However, it is not clear to me whether this is related to the mitogenesis pathway.

Also very interesting about NAD+/NADH ratio. They are involved in mitogenesis reset and these chemicals are also involved in the rationale for lactate?

http://www.longecity.org/forum/topic/86297-a-protocol-to-upg

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Sat Feb 25, 2017 06:02 PM                   Quote | Reply

Dear ernemef: I am so glad that you are in that class of cancer patients that can be more circumspect and demand a higher level of evidence. Bipolar Androgen Therapy is counter-intuitive and one would want it to be more consensus than controversial before putting one's toe into the water.

Ideally the same would be true for all cancer patients. n=1 experiments may or may not be much more helpful than n=0 experiments. Yet, upon the onset of metastatic illness, usually after extensive traditional therapies have been tried, then non-approved sometimes are almost the only option which has been a focal point of the thread.

I was quite stunned by the liver cancer statistics. I had not fully appreciated the global magnitude of the problem. The latest statistics noted three quarter of a million deaths in 2012, perhaps a million or more this year. And all there is is sorafenib? It took 10 years to think of 2DG?

We need more Warburg thinking!

You really do not need to be a genius, all we need is a conspiracy to tilt the conversation to metabolics. We can simply sideline others by changing the vocabulary. Those who were not talking in metabolese would be the out crowd. In a Tower of Babel scenario, one can simply win the argument through force of demography.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Mon Feb 27, 2017 08:54 PM                   Quote | Reply

Very exciting! A new 3-BP article. PMID:28236852 Not really that new, I think we talked about this one a few months ago, though it is great to see it now in pubmed. This one highlights the considerable importance of GSH in 3-BP effectiveness. Several interesting ideas emerged from the paper for me.1. possibly limiting cysteine in the diet.2. possibly specifically targetting tumors for GSH depletion. 3. use of GSH rescue therapy if trouble were to be encountered with 3-BP. I noted the below url before. The highest dose was able to greatly decrease glutaminase levels. This should reduce glutamate levels. GSH needs glutamate to be synthesized. However, this would not be tumor specific. What might happen to 3-BP safety with maximal whole body GSH depletion? http://www.calithera.com/wp-content/uploads/2016/11/Phase-1- is encouraging to watch the ongoing accumulation of 3-BP research. There is potential and admittedly risk involved with this. Perhaps chitosan acetaminophen might help?

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Mon Feb 27, 2017 10:48 PM                   Quote | Reply

ernemef, very interesting article in the forthcoming April volume of Medical Hypotheses. The hypothesis that is presented is that prostate cancer results from menopause (somewhat indirectly). Look forward to hearing your thoughts.

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RE: Anyone used 3bp (3-bromopyruvate)?
by ernemef on Tue Feb 28, 2017 06:56 AM                   Quote | Reply

Jcancom, for years I have been sucpicious of prostatic infection due to sexual intercourse as a cause of benign prostatic hyperplasia and subsequentally prostate cancer, largely due to the widespread nature of its occurrence. I used to suspect a connection with vaginal fungal infections which are very common, but my GP didn't think much of the idea. She is a woman after all. However the menapausal connection throws new light on the matter. Maybe, maybe. Unfortunatly once you have undergone the transformation to the cancerous state it doesn't help much what the cause was. I wonder what the incidence is for homosexual men.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Tue Feb 28, 2017 06:20 PM                   Quote | Reply

ernemef, there has been so much great cancer news that I have been reading lately that I was thinking that we should call for a global "Cancer is nearly defeated" event for this weekend coming up. With this news about BPH prehaps being pre-malignancy, the idea is all the more relevant.

I had not realized how enlarged the prostate can become with BPH. wiki shows it as this huge growth that covers much of the male urogenital tract. If this were to be a simple infection, then treating with curative intent could help us determine whether BPH does eventually progress to cancer. Considering the symptomatic consequences of BPH I suspect that quite a few guys will now be visiting their doctors for curative antibacterial/antifungal? treatments.

There would be a strong parallel to peptic ulcers and H.pylori. From what I understand BPH is now commonly treated more as a cryptic inflammation than as an infection. This is how ulcers were always treated. Simply treating the inflammation and not the infection probably did not help reduce the risk of stomach cancer, same would be true for BPH. This is a very exciting development and is one of those times where you really have to wonder how this was not convincingly pieced together before. It has been sitting right there for us for decades and no one could put it into words.

Amazing how much great news there is out there, most of which people are largely unaware of. For example, it has been reported in 2015 that a H. pylori vaccine is safe and fairly effective. H. pylori is an essential cofactor in up to 85% of stomach cancer which is currently one of the world's biggest cancer mortaility risks.

Also the report that you mentioned about 177Lu for prostate cancer. Two clinical trials for this are opening up in the States. The hypothesis about the menopausal link to prostate gives us the possibility that in the medium term that most prostate cancer would never manifest.

Report out today that the T-Car trial with Kite has shown almost 40% 6 month complete responders.

Blushwood Tree, immunotherapy, the cell results for 2DG + sorafenib, ...

There is enough good news out there for a celebration (in my opinion).

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RE: Anyone used 3bp (3-bromopyruvate)?
by ipappas on Wed Mar 01, 2017 06:03 PM                   Quote | Reply

Hi J, thanks for keeping the thread alive !

If you noticed, the article you cited PMID:28236852 (do you have the full-text?), is authored by Dr. El Sayed, who treated the patient with metastatic melanoma in Egypt in 2014. He had used paracetamol to deplete tumor glutathione. This means he still believes in this approach and we may see more results coming!

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RE: Anyone used 3bp (3-bromopyruvate)?
by ipappas on Wed Mar 01, 2017 06:28 PM                   Quote | Reply

Hi all, I don't know if you noticed the paper PMID: 28193528, co-authored by our dear friend Danielus! Congratulations!

It discusses at length (quite technical) the abnormalities of intracellular alkalinization along with extracellular acidification typical in solid tumors and leukemic cells and the relationship between pH and the Wardburg effect. It reviews various cellular acidifiers that have shown strong anticancer properties: Salinomycin, Metformin, DCA, 3BP, and others.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Wed Mar 01, 2017 11:18 PM                   Quote | Reply

Dear ipappas:

The 3-BP story continues and the research continues to pile up. The basic story line continues to confirm the basic findings reported 15 years ago.

It is very exciting to see further investigation by the group who treated the melanoma patient (read the article through a library). I think there should be more such clinical reports that are followed up with subsequent theoretical in the scientific literature. Sometimes with clinical reports there are large unresolved question marks that are never addressed. For example, there is still a large mystery of why the original liver patient treated with 3-BP responded in such a massive way. It would be very helpful if this were to be answered.

Yeah, if we were to have another patient report, then I would probably freak (as would many others on the thread). Many of the reports of 3-BP to date have been of very late stage patients, if they could report on one who while late stage also had some reasonable expectation that they could regain health then the entire nature of the discussion would change. How ethical would it then be for end stage patients without treatment options not to have freer access to 3-BP? That would apply to the 8 million cancer patients who are not expected to see it to the end of the year. At the core of our years long 3-BP journey, there has been lurking a profoundly absent sense of basic morality which is not easily attributable to anyone or anything in particular.

The newly cited research clearly opens up a range of new clinical avenues to extend the initial result. I am somewhat concerned though about when normal cells might become vulnerable to knocking down GSH with 3-BP treatment.

I just realized that the Ko group also have a GSH article out PMID:27582536 from October. It is quite interesting to see how the two groups wrote on the same topic, though had different spins.

With  PMID:27582536, I was interested in the finding that glutathione S-transferase is the enzyme that forms the 3-BP-GSH conjugates. Wonder if you might be able to get around having to lower GSH levels and simply knock down  glutathione S-transferase. At least this might be interesting to look at in cells.

The article also reported for the first time that 3-BP actually upregulates GSH related genes. That is quite interesting. Some people might introduce resistance to 3-BP by simply dosing up too slowly. The GSH genes would increase and then oppose 3-BP.

Also like how both articles noted the importance of reducing GSH over simply upping 3-BP and consequently its risk. The Minimal Inhibition Concentration decreased by up to 8 times by simply adding a GSH depletor in the earlier article. These articles highlight for me how much of the so called informed commentary related to 3-BP has instead been ill-informed. For example, most popular reports on PMID:24636230 suggested that 3-BP had not been successful. This is largely untrue. Figure 3 (at the right) shows a near disappearance in LDH. The current articles can shed some light on how to interpret the Figure. When the LDH level fell by 25% (4000--> 3000) with a low dose of 3-BP, this should suggest that perhaps GSH is countering the effectivenss of 3-BP. As more doses of mono 3-BP are applied the LDH continues to decline to around 1500, perhaps a 60% decline. This should give yet more hints of the opposing effect of GSH. 3-BP is working, it is entering the cell though there is some pushback (perhaps GSH?). Then when the paracetamol is combined the LDH plunges to 12! LDH has declined by 99.8%!!! It is a large stretch to consider this some great example of how 3-BP was ineffective, as was widely reported. 3-BP needed a little help and then it had a massive effect. The October report noted, though that optimizing 3-BP once it has reached the inside of the cell is not truly the real challenge. 3-BP has so much inherent power to destroy cancer cells once in the cytoplasm that it removing these blocks such as GSH really should not be overly strenuous. The big problem though is simply attaining cell entry. Both of these articles took months and months (approaching a year) to be formally published. It does not seem unreasonable to me that these articles could be added to pubmed once they are received and then corrected/edited. I am not sure whether that is how it works, though 8 months seems a rediculously glacial time frame. Even the article that has only been uploaded to pubmed within the last few days already seems dated. For intance it does not cite the article also on 3-BP and GSH nor does it cite the article that researched the proteome and 3-BP. Having such a highly deliberated publishing model results in research that is hot off the press being somewhat stale. Quote | Reply

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Mar 02, 2017 08:41 PM                   Quote | Reply

Early stage, though plausible. I think the thead commented on this anti-malarial approach a few years back.

PMID:26461094

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Fri Mar 03, 2017 11:33 PM                   Quote | Reply

A long standing mystery on the thread is the identity of tow liver patients treated with 3-BP as reported on the Hopkins site. Might have found them.

The Ministry of Health in Israel granted permission for 3-BrPA treatment "under the compassionate use protocol in two clinical patients who received the drug intra-arterially. In both cases, patients were diagnosed with end-stage liver cancer (HCC and cholangiocarcinoma, respectively). As a result, both treatments were technically successful and no drug-related toxicities were recorded." PMID:26989470 And as a followup to PMID:25569102 with the quite startling comment that ccRCC has a near absence of mitochondria, there was this PMID:27418963. I have wondered if there might be any interest from the ccRCC community in 3-BP.A fair amount of 3-BP research seems to be below the radar. Two of the above articles do not pull up under a search for 3-BP. Is there a way to search pubmed that would search articles for the text "bromopyruvate"? Quote | Reply

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Sun Mar 05, 2017 02:32 PM                   Quote | Reply

Congratulations to Germany for upholding patient choice and respecting fundamental human rights! Given German medical law it is no great surprise that the initial published 3-BP patient was treated there, a point that has not been stressed enough on our thread.

No other nation allow for human treatment with little more than pre-clinical mouse research. This innovation bottleneck is a central feature of the minimal progress that has been made in biomedical research.

The German recognition of the sanctity of the patient doctor relationship outside of democratic inteference  demonstrates a commitement to freedom. Further, allowing decisions to be made at a local level creates an innovation driver (as was seen with 3-BP). Central planning failed? Who knew?

With the massive amount of pre-clinical research that is constantly being published, patients in need of innovative medical treatment should be aware that Germany might offer them options within their established medical system that would not be available anywhere else in the world.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Sun Mar 05, 2017 08:25 PM                   Quote | Reply

Interesting Germany has recently changed the prescription status of 3-BP. How would a doctor write a prescripiton for a drug which has not been approved?

http://www.bfarm.de/SharedDocs/Risikoinformationen/Pharmakov

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Sun Mar 05, 2017 08:42 PM                   Quote | Reply

Finder, your help would be appreciated.

Does the above url imply that 3-BP is currently within the authority of the Pharmacovigilance Division of Bfarm?

This is confusing. The FDA would not convolute 3-BP with other products in its Orange book. It appears that this is being done with 3-BP at Bfarm.

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RE: Anyone used 3bp (3-bromopyruvate)?
by dumbcritic on Mon Mar 06, 2017 08:38 AM                   Quote | Reply

I'm guessing it's due to what happened in Brüggen-Bracht. I wonder if compassionate use will still be allowed?

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Mon Mar 06, 2017 09:32 PM                   Quote | Reply

critic, I have also been thinking along compassionate lines. Why have they stopped compassionate use? This seems very strange to me. The FDA went through a thorough analysis of the evidence and concluded that a phase 1 clinical trial with 3-BP was warranted. The clinical trial has yet to start after all of these years, though why not have a compassionate use program? Compassionate use through perhaps Hopkins could would not need the formal structure or cost of a formal clinical trial, though could gather valuable information in terms of patient response etc.

Quite exciting to see that a second edition of Tripping over the Truth was published last month. The narrative of the Metabolic thought leaders that has been central to much of our online discussions has largely been maintained.

I had started to wonder whether there might yet be a way to the goal line for the Somatic Mutation Theory, though the book continues to strongly rebut this theory. Book also notes that a metabolic clinic in Turkey has applied many familars such as 2DG, DCA, ketogenic, etc. and appears to report a fair amount of success. Love to know whether they have also used 3-BP.

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RE: Anyone used 3bp (3-bromopyruvate)?
by entery on Thu Mar 09, 2017 03:50 PM                   Quote | Reply

Hi everyone!

Does anyone know about a clinic preferably in Europe, that can help me with getting a central venous catheter (port) ?

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RE: Anyone used 3bp (3-bromopyruvate)?
by Danielus on Thu Mar 09, 2017 04:20 PM                   Quote | Reply

Hi, most in Germany if you are sent by a doctor (e.g. from cancer private clinics).

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RE: Anyone used 3bp (3-bromopyruvate)?
by entery on Thu Mar 09, 2017 04:30 PM                   Quote | Reply

Hi Daniel,

I would not be sent by any doctor, since it would not be used for any conventional treatment.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Danielus on Thu Mar 09, 2017 04:57 PM                   Quote | Reply

Hi Entery, that is why I mentioned cancer treatment clinics - there are many in Germany - you could go to one of thise a few times (one that has a Dr. not a Naturopath) and also ask the Dr. for a letter to instal a port-a-cath.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Danielus on Thu Mar 09, 2017 04:58 PM                   Quote | Reply

I meant a small private cancer clinic.

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RE: Anyone used 3bp (3-bromopyruvate)?
by entery on Thu Mar 09, 2017 06:15 PM                   Quote | Reply

Thanks Daniel, I will consider that. I have tried using peripheral venous catheter for some time now, but I don't think it will work when I start with 2DG and 3BP.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Danielus on Thu Mar 09, 2017 06:22 PM                   Quote | Reply

You are welcome Entery. For 2DG I havent heard of issues but 3BP, to my knowledge, will be best with a port.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Mar 09, 2017 06:51 PM                   Quote | Reply

entery, would be a very good idea to have some GSH on hand.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Sat Mar 11, 2017 03:52 PM                   Quote | Reply

Very exciting news!

FDA management is changing and with it the possibility that their regulatory stance on issues that we have constantly discussed over the last many years might actually budge. Probably most importantly there can be at least a moment in which our state of consciousness can shift and an important lesson can be learned: life does not have to be an endless repeat of the past.

That is worth repeating! Life really does not have to be the same as it always was.

The FDA might finally be exiting Einsteins's insanity loop.

That is:

1. Fail

2. Go to back to 1

The fact that nearly all stage standardized solid cancer mortaility rates have remained unchanged for at least 50 years has to be recognized as failure.

It is self-apparently true that if the FDA changes the rules of the game wisely, then there will be a powerful wave of biomedical progress that will clearly be apparent to the patient communities. Basically, we will know that they made the right changes when the medicines of the future finally move from the lab to patients. We'll have to monitor whether this a real or cosmetic change.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Sun Mar 12, 2017 12:21 AM                   Quote | Reply

Been thinking about how FDA policy changes could help move things forward. Very excited! All this talk of moon shots and we are still on the launch pad even after a trillion dollars of government investment. If they could simply adjust some of the rules, another trillion dollars and still awaiting ignition would not have to happen.

For instance, why not simply extend an unlimited Right to Try for those who have life expectancies of at most a few months? Posters on our thread have talked about their fears of how treating their terminally ill loved ones might result in professional misconduct charges applying to those you were hleping them. Combining such an interpretation of Right To Try with a Duty to Report would be a powerful innovation driver. For instance, consider how this could drive 3-BP forward if of 1000 terminal cancer patients even 10 had a response even close to that of the two published patients we refer to constantly on our thread.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Wed Mar 15, 2017 06:55 PM                   Quote | Reply

Appears to be some developing news on the Bracht investigation. The report is expected by the end of this month.

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RE: Anyone used 3bp (3-bromopyruvate)?
by peggyznd on Thu Mar 16, 2017 12:05 AM                   Quote | Reply

Jcancom, Re your reference to 3BP "even 10 had a response even close to that of the two published patients". Concerned that phrase may be interpreted by some readers to think that these two patients were somehow cured, or had long-term benefit.

In the situation of the young liver cancer patient, he was thought to have died of liver failure, though no autopsy was done. THat is not the outcome that anyone wanted, of course. He had had some limited response to another FDA-approved drug, used off-label, but with the first treatment of 3BP, went into a coma, and after a total of 9 treatments, went into liver failure and died.

Not exactly the response that we would want for other patients. Let us be more precise about what we know and not imply something that is not factual. This is too important to create misperceptions.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Danielus on Thu Mar 16, 2017 05:16 AM                   Quote | Reply

Dear Peggy,

Let’s not mislead people here, which I see you are constantly doing.

Regarding the liver cancer patient:

1. The published article is clearly showing the effectiveness of 3BP in the case of the boy, a substance that extended his life. This evidence is represented by at least two major institutions of this world, i.e. John Hopkins University of USA and Frankfurt University Hospital of Germany. Not to speak about the people representing those institutions who each of them are world leaders of both science and clinical interventions in their fields.

2. The father of the boy, a scientist himself, can demonstrate step by step with impressive scientific evidence that 3BP was extremely valuable for his dear son, and that was the reason why his dear son could live more. If you like to contact him, I am sure you will find his contact details at the Dutch University he is working for

These are facts, no questions.

Now I am asking the people reading this, what should we do? Listen to someone like you who constantly is trying to push 3BP in to the negative light or listen to some of the best scientist and medical doctors of this world.

The choice is in our hands on selecting the value and filtering out the noise that is created by various people with various reasons, believes or needs behind.

Let’s not forget, that as it was discovered some time ago and shared with all here there is a Forbes article indicating that every now and then, Peggy was financially supported by some of the largest Pharma companies of this world. That tells me there is a conscious  or unconscious bias is her judgement and statements.

The point is that I am a little tired of all this noise, intended or un intended.

Check the facts. Not the stories. There is both scientific and clinical evidence published by some of the best of this world showing the positive facts regarding 3BP. The rest is noise.

Kind regards,

Daniel

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RE: Anyone used 3bp (3-bromopyruvate)?
by dumbcritic on Thu Mar 16, 2017 07:04 AM                   Quote | Reply

''Initial results with Sorafenib were encouraging. Thus, tumor growth appeared to have halted during the first 2 months of Sorafenib application, even with some regression of tumor volume. However, after 6 months, CT scans indicated a renewed expansion of the tumor’s mass, and Sorafenib treatment was halted. 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. On the basis of this condition, a duodenal feeding tube was installed and continuous (24 h) enteral feeding was started. The caloric intake was adjusted to 2000–3000 kCalories per day.''

''Due to a large tumor burden at the presentation, it was determined to try to obtain a very high dosing with 3BP in the first treatment month. A second treatment was scheduled 2 weeks after the first, the third after 4 weeks. After the second application (128 mg), which went without any acute problems, the patient started to get disturbed. Four days later, the patient went into a hepatic coma and was hospitalized. The diagnosis was hepatic coma, which usually results in death. It was suspected that the patient was undergoing a potential tumor lysis syndrome (TLS) after three 3BP treatments. Without additional help from the hospital, the patient was allowed to leave the hospital by ambulance and transferred back home. After 4 h at home, he began to show signs of recovery, and by nightfall, he was completely back to baseline, with most of his mental capabilities functioning. The recovery continued over the next day. The patient was able to consume food and have social interactions with his friends, without any memory of the comatic phase. The treatment team, in close communication with the patient and his parents, and with their consent, decided to continue with the 3BP treatment as scheduled, with modifications in which the blood chemistry was carefully monitored. Especially, ammonia, urea, and potassium were added to the weekly schedule for monitoring. A medication for reducing blood ammonia in liver cancer patients, Hepamerz was prescribed (6000 mg/day) and used for the patient as needed, but always following application of 3BP.''

''Pre existing ascites and edema continued to be a major problem for the patient, and despite daily exercise, his mobility continued to be limited. However, during the summer of 2009 he started to regain his physical strength and went out in his wheelchair regularly for a promenade. In addition, the patient celebrated his 18th birthday at his home surrounded by many friends and family members on September 9, 2009. The photo of the patient in Fig. 5 was taken on his birthday. At the end of October 2009, a part of the discomforting ascites was removed by CT-guided puncture. 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. In December 2009 the edema and ascites were becoming more problematic. Liver functions were overloaded due to rapid destruction of the tumor cells resulting in the liver’s inefficient detoxification. Despite regeneration of the healthy liver cells, this process apparently could not compensate adequately for the rapid destruction of tumor cells and could not detoxify the dead cancer cell debris fast enough. Consequently, the blood albumin levels were decreasing. The patient passed away 2 years after his first diagnosis due to an overload of liver function. The patient (Fig. 5) 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.''

Taken from the free PDF https://link.springer.com/article/10.1007%2Fs10863-012-9417-

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Mar 16, 2017 06:02 PM                   Quote | Reply

critic, good one! Other commentators of 3-BP have pulled out a long quote from this article and then have created their own interpretation based upon the assumption that no one will even actually bother reading the quote (or the article).

Let the people read the article and decide for themselves! It is hard to imagine that anything but a favorable impression of 3-BP would emerge relating to the treatment of this specific patient.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Mar 16, 2017 06:07 PM                   Quote | Reply

I have actually followed my own advice and several interesting aspects of the article came into focus for me. The Sorafenib that they treated with (I have learned recently) has a 2% response rate, where the responses typically appear to be short-lived (28 days?). The patient in the article experienced tumor stabilization if not perhaps a regression, though this might not actually qualify as a response (perhaps at least a 20% reduction is a more typical minimum). Even still the patient continue to detiorate symptomatically.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Mar 16, 2017 06:12 PM                   Quote | Reply

I was also interested in what they followed up with: TACE Gemcitabine and Cisplatin.

They performed one treatment but it was found that these chemos were so cytotoxic that they decided against using them again. In fact, even while the patient was now in an emerging end stage of his illness it was thought best to treat with no additional approved medications but instead wait a month for authorization to treat with 3-BP. An immediate bolus dose was give when this approval was authorized.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Mar 16, 2017 06:21 PM                   Quote | Reply

I have been unsure on this point for years. Does 3-BP actually contribute meaningfully to the therapeutic options of those patients who can undergo TACE? I mean how high a hurdle is it for even a chemo drug to destroy cancer cells when you are essentially delivering the drug directly to the region of the cancer?

Apparently this is a hurdle too high sometimes for chemo. The liver patient received the standard of care to the book and even though he was in a near pre-morbid state decided to wait one month for 3-BP treatment while offering no other supplemental treatments.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Mar 16, 2017 06:27 PM                   Quote | Reply

"The patient (Fig.5) 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."

One of the authors of the article after the Bracht incident has retracted the above statement. However, in carefully reading the article is very hard to understand why the statement would need to be retracted: the above statement appears entirely consistent with the text of the article. The liver patient had been in a nearly constant symptomatic decline for 9 months before starting on 3-BP. Yet, within hours of the first 3-BP appears to have regained his appetite. He continued to enjoy symptomatic benefits from 3-BP treatment for 11 months.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Mar 16, 2017 06:39 PM                   Quote | Reply

I have been thinking lately of how the FDA could demonstrate that they are sincerely interested in embracing meaningful regulatory change. The idea of allowing for approval designations without requiring efficicay demonstrations has been suggested. However, it has occurred to me that 3-BP really does not need such a change: 3-BP could easily demonstrate efficacy measures if different measures were allowed for approval. The reasoning being that proving long term survival benefits would likely take a long time, probably years and a large amount of money. If we were to move to an efficacy measure such as reduction in metabollicaly active tumore mass then that is something that 3-BP can achieve within 15 minutes.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Mar 16, 2017 06:47 PM                   Quote | Reply

Without 3-BP being given some level of officially recognized approved, we are stuck in the strange circumstance that mainstream medicine sometimes feels that the best treatment option is to withhold all further treatment as noted above instead of offering their patients the most powerful known cytostatic drug ("The rate of tumor necrosis due to 3BP treatment seems to exceed all known cytostatic drugs" .) [quoted from the liver patient article] {Wouldn't cytotoxic be the more appropriate word than cytostatic?}

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Mar 16, 2017 06:55 PM                   Quote | Reply

In terms of actual cure of long term response by the liver patient or melanoma patient, no it is true that they did not achieve this. However, these patients were specifically selected on the basis that they did not have long term survival potential. Notably even though both had truly large tumor burdens when 3-BP treatment started neither of the patients appeared to have metabolically active cancer detectable on their last labs.

Where I was going with if "even 10 had a response close ..." was that if you were to treat patients who actually had a functioning liver (liver patient had 5% liver function) and a functioning lung ( melanoma patient had perhaps 50% lung funciton) then you could start to see unquestionable benefits in terms of survival etc. Apparently, the stage IV lung patient treated with 3-BP from Columbia achieved these milestones.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Mar 16, 2017 07:01 PM                   Quote | Reply

Perhaps the real point of note is that the patient benefited from his treatment. There is no way that I could imagine that he would have been smiling on his 18th birthday photo without 3-BP treatment. It seems nearly impossible to imagine that he would have even be alive. The approved treatments that he received did not even provide him with a short term symptomatic boost.

Basically, his response is exactly what we would want for others. The two patients had truly overwhelming responses. I totally agree this is too important to create misperceptions.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Mar 16, 2017 07:09 PM                   Quote | Reply

One aspect that some readers of the thread might not be fully aware of is that the reason why he went into a coma after the second treatment round is that TLS developed. TLS? 3-BP was so overwhelmingly effective for this patient as an anti-cancer drug that too many cancer cells were killed. 3-BP kills too many cancer cells? First world problem? 3-BP is one of the first cancer drugs that you have more therapeutic index under the hood than you actually need. Same problem in the melanoma patient: 99.8% reduction in LDH. Almost more cancer destruction than is desirable at any given time. Liver patient's demise is likely attributable to too much cancer destruction not enough liver function.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Mar 16, 2017 07:41 PM                   Quote | Reply

Sorry for hogging the mic, though it is one way of preventing others from just making things up.

Appears the possible outcome of the Bracht investigation is currently in evolution. We should know in about 2 weeks.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Mar 16, 2017 08:20 PM                   Quote | Reply

That's interesting.

In the write up of the melanoma patient, they quote 2-3.5 mg/kg 3-BP dosage from the liver patient article as their treatment guide. What is strange is that the quote from the liver patient article is referring to 3-BP TACE not IV.

Stranger still is that even with what appears to be an enormous dose reduction, they still reported a 99.8% reduction in LDH production from the tumor.

It would be of enormous help if a phase 1 trial could be done to help clarify such issues.

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RE: Anyone used 3bp (3-bromopyruvate)?
by peggyznd on Thu Mar 16, 2017 09:15 PM                   Quote | Reply

I stand by my statement that we must be careful not to imply by any statements that 3-BP (or any other compound,what ever it is) can be valuable in cancer treatment on the basis of the responses in the two patients referenced at the beginning of this thread. Since I am most familiar with the young man who had an extremely rare liver cancer, and whose cancer was essentially untreatable per the history, his story may or may not have relevance for cancer as a whole, nor even for liver cancers as a group.

It is the story of a teenage who was treated under dire circumstances, first with a drug sorafenib/Nexavar which had been recently approved in the USA in 12/2005 for adult kidney cancer patients who had progression despite earlier failed treatments. The Progression Free Survival for the responding group was 167 DAYS, with just 2% of kidney cancer patients having a partial response. Stats from the Phase III trial in hepatocellular carcinoma (a more common liver cancer) showed a median TTP (Time to Progression of disease) of 2.8 months. Sadly, this must have been the most rationale drug to give this boy, and required special permission to do so, as it had never been tested in that age group.

Per the report, he had an initial response, which was remarkable, but that was discontinued due to rising liver measures that exceeded the tolerable levels. After six months of treatment--nearly twice the length of time of the median in the trials--there was more tumor growth. The boy's health had deteriorated and he was put on a feeding tube.

By this time, requests were made to access 3BP in early 2009, but before permission came, and with the grim situation, chemo meds were given, along with other meds. Concerned with interaction of these meds with the forthcoming 3BP, chemo was halted, and 3BP began.

This was two treatments in one day, the patient was discharged to go home, and he seemed to have an appetite. TWo weeks later, he received another treatment and went into a coma four days later. Sent home from the hospital in the coma, the boy began to recover.

Additional treatments followed, and with some improvement in his general health, but by the end of year, the boy had died, reportedly "due an overlaod of liver function."

Case studies are often the basis for designing Phase I trial which test the safety of the proposed meds. This case study, despite its obvious disappointing results, may have value in creating a such a trial.

Similarly, this case study also reveals that there was a relatively lengthy response to the use of sorafenib, in a cancer, never previously treated, and iwth greater duration of response than with the other liver cancer types. This may also lead to a Phase I trial, also valuable. One might also ask if the sequence use of sorafenib, followed by the chemo and then the 3BP was the cause for the extra months he seemed to have gained.

Beyond that, we need to be cautious about what any of these limited case report mean to treatment as a whole. Pretty defensible approach and protective of patients who with grim prognosis.

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RE: Anyone used 3bp (3-bromopyruvate)?
by Jcancom on Thu Mar 16, 2017 10:05 PM                   Quote | Reply

Anyone know why  http://www.3bpko.com/ is now open?

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RE: Anyone used 3bp (3-bromopyruvate)?
by kccoc on Sat Mar 18, 2017 10:52 AM                   Quote | Reply

and we stand by the following statemets by Danielus;

1. "Dear Peggy, Let’s not mislead people here, which I see you are constantly doing."

2. " ....every now and then, Peggy was financially supported by some of the largest Pharma companies of this world. That tells me there is a conscious  or unconscious bias is her judgement and statements"

By that, we need to be cautious.

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RE: Anyone used 3bp (3-bromopyruvate)?
by peggyznd on Sat Mar 18, 2017 12:37 PM                   Quote | Reply

Please do clarify what you think is misleading as to how I have discussed 3BP and its use in the single young liver cancer patient from the published report. This case study is just that, a part of a larger discussion, does not provide any objective proof to support its use for cancer patients as a whole. It does not even describe the exact formulation of 3BP, rather just "speciallly formulated 3BP (patented and proprietary)". To point out this basic lack of information and to explain the range of treatments given to the young patient is not misleading.

I am concerned that there is too little known about the drug to promote it as if it were a safe and effective therapy. That is not misleading, simply cautious.

I acknowledge openly here and in my other patient advocacy work that I have twice a year served on an ethic committee for Roche, along with a number of academic leaders and internationally prominent human rights advocates. In that setting, I advocate for the patient's rights to a good trial design, respectful treatment and a chance to stay on their drug, should it be beneficial. In addition, 3-4 times a year I speak to oncology nurses and some sales staff about my own experience receiving a medication, Proleukin (Prometheus Labs) which savedmy life. For that I receive a small check, a flight to the meeting, a stay in an airport hotel, and the opportunity to tell those nurses what it like to be desperate for a cure from kidney cancer and melanoma. Other than that, I live on savings and Social Security, glad to be alive to be able to do so.

I also am a volunteer in a number of patient advocacy groups, especially centered around kidney cancer education, lobbying for federal funds for additional research, or just simply explaining treatment options.

Do point out to me any particulars of any bias which you see, and we can discuss it openly. It is indeed appropriate to be cautious and clear-headed about any of the meds and therapies which are promoted to us patients. We must carefully review the facts, assess them objectively, and tender warnings when warranted.

Peggyzuckerman@gmail.com

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