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Jcancom
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This is from the wiki article on omega-3 fatty acids. The second column has x:y where x is the number of carbons and 6 is the number of double bonds. Simple DHA has the most at 6; so does nisinic acid.

D, the metabolic story just goes on and on. It is startling. Often we wind up right back with drugs that we are all too familiar with. The 3-BP --> diclofenac plan above is especially intriguing. The escape routes for cancer are narrower and narrower. On the DCA thread we talked about how to strategically plan the second treatment for maximal effect. With this 3-BP- diclofenac treatment, one could evolve the cancer into a trap. The more of these traps that we find the stronger is our ability to control the cancer. It seems we are approaching a knowledge level in which cancer has no viable counter-strategy.

Best Wishes, J 

 

Hexadecatrienoic acid (HTA) 16:3 (n-3) all-cis-7,10,13-hexadecatrienoic acid
α-Linolenic acid (ALA) 18:3 (n-3) all-cis-9,12,15-octadecatrienoic acid
Stearidonic acid (SDA) 18:4 (n-3) all-cis-6,9,12,15-octadecatetraenoic acid
Eicosatrienoic acid (ETE) 20:3 (n-3) all-cis-11,14,17-eicosatrienoic acid
Eicosatetraenoic acid (ETA) 20:4 (n-3) all-cis-8,11,14,17-eicosatetraenoic acid
Eicosapentaenoic acid (EPA) 20:5 (n-3) all-cis-5,8,11,14,17-eicosapentaenoic acid
Heneicosapentaenoic acid (HPA) 21:5 (n-3) all-cis-6,9,12,15,18-heneicosapentaenoic acid
Docosapentaenoic acid (DPA),
Clupanodonic acid
22:5 (n-3) all-cis-7,10,13,16,19-docosapentaenoic acid
Docosahexaenoic acid (DHA) 22:6 (n-3) all-cis-4,7,10,13,16,19-docosahexaenoic acid
Tetracosapentaenoic acid 24:5 (n-3) all-cis-9,12,15,18,21-tetracosapentaenoic acid
Tetracosahexaenoic acid (Nisinic acid) 24:6 (n-3) all-cis-6,9,12,15,18,21-tetracosahexaenoic acid

 

 


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Daniel
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@jcancom Hi J,

Thank you for the list and nice to hear from you, like always.

Once, we should organize a meeting with Manuel and other friends around 🙂

We can discuss all the things we have learned over the years since we started to first discuss 3BP in the Cancer Compass forum, about 7 years ago .... btw, we should celebrate that somehow ... maybe with a new post on 3BP or metabolic inhibitors in general? 🙂

It's amazing that after all this time, metabolic inhibitors are still not mainstream. Have you seen the news about 2DG in India?

We are conducting a clinical trial in India, in a conventional hospital, and the doctors there have started to implement 2DG not only in oncology patients but also Corona. And the results were great! Some weeks ago we had a call from a doctor from India soooo happy that they started to save lives with 2DG. One man with oxygen levels in the range of 45 (yes crazy) got his oxygen to 70 in about 5 minutes after applying 2DG!

Actually prof Lampidis asked me to publish on Cancer Treatments one article on 2DG and Corona many months ago, but I did not have the chance to do that. 

The point is that metabolic inhibitors are great tools and can save lives both in Oncology filed and other area where metabolism is key (where not?).

Kind regards,
Daniel

 


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Jcancom
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D, that is impressive! Non-Western nations clearly are now the innovation leaders in medicine. It has been so disappointing to see a complete lack of willingness to investigate new treatment approaches in cancer (especially metabolic ones). Most of the clinical leadership for 3-BP has occurred outside of Western mainstream medicine.   

COVID has underlined how much Western medicine has abandoned empirical science. The example that you gave of an almost immediate response to 2-DG highlights a lack of commitment to observational learnings.

D, Corona shows the terrific power of metabolics when resistance is not involved. Without the disease fighting back, patients can receive a large benefit. The problem that we face with cancer is that after round 1 the cancer regroups for another round and another. This is why we have building up the knowledge base over all of these years; we need to have multiple rounds of treatment to respond to cancer resistance.  

A resource such as this forum is of great value to all those struggling with cancer as trying to piece all of this together while caring for or coping with cancer would be much too much. There is an enormous amount of research to try and process and we have only been able to extract a tiny fraction of the total of this research. I am always waiting for that next insight that will push us past the line. I will be very interested in any summary that you might create for all of our efforts.

 


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Jcancom
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Another metabolic? We have often discussed proton pump inhibitors (PPI) on forum. It had never occurred to me that PPIs are highly related to the metabolic perspective: proton pumps are what power mitochondrial OXPHOS! Clearly, this is highly central to metabolics. I had thought that PPIs might be more limited to the cell membrane more than the mitochondria.

Well, if PPIs are directed to the mitochondrial energy supply through OXPHOS that is highly interesting. One might imagine inhibiting the OXHPOS complexes and the proton pumps for added effect. this might be a particularly opportune time to try a formulation (such as chitosan) to direct the treatment directly to the cancer cells, as there can be problems when giving PPIs to all cells (they have a certain toxicity through long term use to mitochondria).

 


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Daniel
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@jcancom Very good point J. 

They do act on lysosomes and as a result they are interfering with autophagy https://pubmed.ncbi.nlm.nih.gov/23478938/  

Along the line of your thoughts, this is interesting: 

Proton pumps are also important in the transport of various substances in the body, as we will see in detail in later sections. And while proton pump inhibitors are designed to interact specifically with the hydrogen/potassium pump in parietal cells of the stomach, research suggests that they likely have nonspecific binding capabilities (3). In other words, their chemical structure enables them to bind to other proton pumps as well. Though PPIs don’t stay in the blood for very long, their binding to proton pumps is essentially irreversible—they will continue to inhibit the proton pump until the master antioxidant glutathione is able to facilitate dissociation (4). https://kresserinstitute.com/dangers-proton-pump-inhibitors/

Glutathione inhibition should increase their effectiveness if that is desired.

We would need to understand what other PPIs they interact with besides their well known target.

Kind regards,
Daniel


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Jcancom
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D, I am not sure if I have this correct, though aren't the OXPHOS subunit themselves proton pumps? They could stop the H+ from being expelled from the mitochondrial matrix. Proton pump inhibitors are very widely prescribed medicines for stomach reflux disease.

I was also thinking about your recent imipramine post. In order for macropinocytosis the actin cytoskeleton needs to remodel. Doesn't fenbendazole interfere with actin? Might be an interesting combination.

 

https://www.nature.com/articles/cddis201067

https://www.frontiersin.org/articles/10.3389/fphar.2016.00452/full


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Jcancom
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Back in 2015, a mito formulation for 3-BP was published. Linking up TPP to 3-BP and thus dragging it into the mitochondria was shown to have large anti-cancer effects in cells. However, no in vivo was included in the article. I have been waiting to see what would happen if this were to go in vivo.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335358/

 

 

As we see here in the cell study, TPP 3-BP was 1-2 LOGS! more potent than 3-BP.

 

 

 

 

 

 

Now we have a new mito-3-BP formulation. This time they also included cancer stem cell targeting with HA and also treated with NIR laser. This one had very large anti-cancer effects. Usually in a well established cancer model even slowing down the growth of cancer is difficult; with this treatment, cancer volume began to decline with days of treatment. Selectively removing cancer stem cells essentially takes away the driving force of cancer growth. Cancer stem cells are what sustain cancer growth while the rest of the tumor bulk merely make up the mass of the cells. It is not clear to me how far the laser would penetrate into the tumor, nor how applicable this wold be to human patients. However, this is a very impressive result. 

This research reported that the mito-3-BP did not appear to be toxic to any of the organ systems of the mice.

PMID: 34990518


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Jcancom
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After posting the above formulations I went through the many other formulations of 3-BP that have been published over the last few years; I count ~17. It is quite impressive.

I then reviewed one of the first formulations-- beta-cyclodextrin. As can be seen below this formulation had very large anti-cancer effects in a pancreatic model.This is a highly powerful result. They injected the mice with the pancreatic cancer cells and then just systemically treated with beta-CD-3BP. This is what cancer treatment has always wanted to achieve! Simply inject the cancer treatment and let it find its target with minimal side-effects-- That's what happened! This represents near precision cancer treatment.

The procedure that they used to formulate the drug was extremely simply. 3-BP + beta cyclodextrin (in DI water) sonicate -- shake - freeze- lyophilized. Cyclodextrin is merely a circular form of glucose; when the CD arrives at the cancer site it dissolves due to the acidity; releasing the 3-BP. 

On the left below we see the control mice. They had massive tumors after 1 month. The mice on the right that were treated with b-CD-3BP had minimal tumors. The graph below shows that there was essentially no tumor growth after 1 month with the treatment.

What is also of interest is that there was no combination treatment given. One might expect that citrate cotreatment with 3-BP would amplify the results as has been seen in previous research, though this and other synergistic treatment was not attempted.   

This research was published in 2014, though it is still of substantial relevance today. While we have briefly mentioned this result on forum before, I do not think that it was highlighted enough. Even though it is a remarkably simple formulation-- it is also extremely powerful. This is one of the few 3-BP formulations that could target cancer cells anywhere in the body without the physical limitations of laser, ultrasound etc..

 

 

 

 

 

 


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Jcancom
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Sorry here is the url for the article on pubmed.

https://pubmed.ncbi.nlm.nih.gov/25326230/


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Daniel
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 @jcancom 

Thank you, J. Very interesting and simple formulation. This is what I would have tried several years "at home".

Kind regards,
Daniel


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Jcancom
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D, there is so much cancer research that we have reviewed over the years and it is difficult to put it all together, though the Beta-cyclodextrin- 3-BP treatment appears to be a very very strong one. It has taken us so many years to think the many potential ideas, though this one would seem to be one of the strongest.

I think that we talked about this one on the cancer compass soon after it was published. From what I remember there was some resentment at how they made straight 3-BP appear toxic. This had not seen with the original research, though one could well imagine that they chose the dose just high enough so that 3-BP would seem toxic without the cyclodextrin. In the study they injected 5 mg/kg bare 3-BP which would be expected to cause considerable toxicity and it did.  

Even still, we have seen how injecting bare 3-BP can cause vein irritation. This is as expected as 3-BP can produce HBr which is a strong acid. Using the cyclodextrin formulation would be a reasonable way to increase patient comfort to avoid such vein problems. Also the cyclodextrin formulation would tend to further concentrate the 3-BP in the tumor environment which would also be a win for the patient. 

beta-cyclodextrin 3-BP might be one of the best treatments that could be placed near the top of a treatment program. As can be seen above in the figure on the right, even monotherapy with this approach yields massive tumor reduction. Remember with Jess, Gemcitabine was placed as the central treatment and then everything was just added on top of that. This did have a powerful anti-cancer effect (yet much of this power actually appears to have been related to the metabolic add-ons that Jess treated with including 3-BP), though depending on chemo locks you into roller coaster in which eventually the cancer will enter an uncontrollable growth stage even with side effects along the way. Patients can misinterpret the decline in tumor markers as real progress against the cancer, when in fact it is mostly just a futile process of selecting those cancer cells that are chemo resistant. Oncologists that can avoid chemotherapy clearly have a great deal of treatment expertise.

As we see in the middle picture above, Gemcitabine monotherapy had minimal anti-cancer effect in the pancreatic model. You really need a top treatment that you can work around, yet chemotherapy itself  offer low treatment power. If you want to move away from the standard of surgery, chemotherapy and radiation, then you need a powerful top line treatment. The above figure suggests that beta-cyclodextrin 3-BP could be such a treatment.

As soon as you have this powerful top line metabolic treatment, there are so many cotreatments that you could consider. With 3-BP, citrate, curcumin, methyl jasmonate, DCA, Fenbendazole, silver nanoparticles, oncolytic viruses, genistein, methylglyoxal, ketogenic diet, paracetamol etc. would then all have potential to amplify the response. Remarkably, in the above research, they did not even bother pursuing such combinations as the monotherapy itself had such a strong showing.

I was somewhat disappointed, though, when reading through the b-CD-3BP patent to find that the apparent intention is to combine with radiation and standard chemotherapy. It would seem more powerful to chart out a new pure metabolic treatment approach. I was surprised when I read the 3-BP citrate combination research that synergy can happen simply by double inhibiting glycolysis with the citrate. Merely inhibiting glycolysis at another glycolytic enzyme with citrate greatly enhanced the treatment power of 3-BP. As noted above several other metabolic inhibitors apparently have the same effect. One really wonders why it would be thought relevant to bring in standard chemo with all of its side-effects when double or triple metabolic inhibition might be free of such complications. This would need to be worked through, once the top line b-CD-3BP were available, then an entire ecosystem of parallel metabolics could emerge.

 

Below is additional results from the above research article. Here we can see the results for caspase-3, MCT-1 and GAPDH for B-CD control, gemcitabine and B-CD-3BP. These figures are quite startling.

The B-CD control on top had a near absence of caspase-3 activity, while having robust MCT1 and GAPDH expression. The tumor as can be seen is simply massive.

The gemcitabine treated mouse only has somewhat activated caspase-3 and reduced MCT-1 and GAPDH expression in comparison to the B-cD control. The 3 B-CD-3BP mice below show enormous caspase-3 activity and minimal activity of MCT-1 and GAPDH. It appears from the H&E column that much of the tumor mass in the B-CD-3BP mice had become a liquified necrotic mass so the expression analysis needed to choose those areas that had not underwent complete metabolic collapse. The one mouse in the middle of the B-CD-3BP group had a somewhat largish tumor mass, though it appears that they might have specifically selected this mouse for analysis as it had the most of any of these mice as seen in the figure above. With the B-CD control and gemcitabine treated mice, all of them appeared to have very large tumor masses.  

What is also of interest is that the next combinations to extend the metabolic collapse for the B-CD3-BP mice would seem obvious. The middle mouse still had some MCT-1 expression, so the initial round of 3-BP was not quite enough. We saw that with the melanoma patient, paracetamol can dramatically enhance the anti-cancer effect of 3-BP. Paracetamol knocks down GSH which acts to block the effects of 3-BP. Removing such a blocker can result in a profound combination effect. Other approaches including OXHPOS inhibition, additional glycolytic inhibition etc. could also amplify the effects beyond monotherapy B-CD-3BP.  

From this base, additional approaches that we have explored on the forum could be applied to weaken cancer from additional angles. What is of particular interest with the initial B-CD-3BP idea is that one would have greatly constrained the metabolic character of the surviving cancer cells. As can be seen below, there is dramatic selection against MCT-1 expression. The article found this to be an unexpected result, however, given the power of 3-BP, it would seem not that unexpected that there would be a dramatic selection against MCT-1 expression. The only cancer cells that could survive would be those without MCT-1 expression. 3-BP would remove all those cancer cells that did express it. This would create an interesting cancer phenotype: namely, the remaining cells would likely be highly constrained in their lactate production. This would be a great win! Lactate causes so many problems! Without an abundance of lactate many good things could happen-- e.g., less metastatic potential, inhibit the reverse Warburg effect, allow for the immune system to respond better against the cancer cells, reduced acidity, ... . Metabolic treatment would create a highly defined change in the cancer environment that would be common for a range of cancer types without reference to the complexities of the internal workings of specific mutations etc of individual cancer cells. Potentially this would allow for a rational metabolic treatment program that would be applicable to cancer in general (instead of trying to treat cancer as idiosyncratic instances). 

It is so discouraging that after all of these years a metabolic approach along the lines that we have discussed for so many years on forum has not emerged. It seems so immoral that patients continue to experience the typical treatment response with gemcitabine as shown above and not that of B-CD-3BP.         

 

 

 

 


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Jcancom
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Wow! This is huge huge news!

Ko Discovery has been given FDA clearance of its IND with a possible start date for a clinical trial for March/April of this year!!! Where did this even come from? I thought they had almost given up on ever starting a 3-Bromopyruvate clinical trial. This is super awesome! As soon as others see that 3-BP is in the game then an entire metabolic ecosystem will evolve. As we have seen over these many years (20 years???) almost any other metabolic treatment will combine strongly with 3-BP. Citrate, methyl jasmonate, silver nanoparticles, recently EM fields, probably oncolytic virus, also probably methylglyoxal and fenbendazole, also ketogenic diet; also genistein; also paracetamol; also DCA, also curcumin. As soon as you have a strong lead treatment (i.e., 3-BP) every else can just amplify the results.

From our current knowledge base this means that cancer should be toast. 3-BP can overwhelm cancer. Combinations should cause truly profound anti-cancer effects. The big worry now is that there is too much anti-cancer effects. 3-BP's main side effect of TLS has caused some problems in the clinic. 3-BP is too good. Cancer clinics really need to stock up on liposomal NAC and Glutathione (GSH). 

Yeah this is amazing! We have waited over 20 years and now finally 3-BP is here. Yeah! There are now almost 10 million annual deaths to cancer; it has become a global crisis. We need something that works: 3-Bromopyruvate works! Wonder if they will disclose the exact formulation?

Funny thing is that I have been waiting for Cage pharma to announce their IND. I guess that there is a race between Ko and Cage to be first to market. Yeah! The more the merrier! Ko is going primary liver; Cage is going pancreatic. I will be very interested to see how they add in co-treatments and other technologies such as genome sequencing to select patients. This is just so amazing. At some point the money feedback effect will occur and this will then go massively large! This treatment could be worth tens of billions in annual sales. In the above figure they showed gemcitabine versus 3-Bromopyruvate. Gemcitabine had close to no effect with pancreatic cancer yet it is a $2billion per year drug. It's almost worthless and it causes large side effects like the loss of hair and it's worth $2 billion? Formulated 3-BP should have no side-effects and it showed truly massive effects without side effects (at least in the above mouse model).

D, I think we deserve an official comment from you on this groundbreaking news! This is the day that changed history. January 22, 2022! Great!

 

 


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Jcancom
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Just to note the 3-BP trial will be a Phase I/ II-A. I do not think that I have ever heard of phase I/II before. 3-BP is such a strong product that it should not be entirely unexpected that the phase I/II could be transformed into a phase 3 trial. Even a small phase I study could produce statistically significant results. What are you supposed to say when perhaps all of the terminal liver cancer patients respond within 15 minutes of a 3-BP injection. How many placebo patients will respond in 15 minutes. With careful selection one could imagine being able to choose those patients with super-responder ability based on MCT-1 status. When news breaks that terminal liver cancer patients are responding to 3-BP there could be a near riot out of the treatment hospital. Even in science there can be a certain resignation to letting the will of the people rule.


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johan
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Hi @jcancom, I can understand your excitement, you've posted relentlessly about 3BP.  Although I understand its potential from a mechanistic point of view, I haven't seen much evidence of successful outcomes in patients. I've read about the recovery of a boy from the Netherlands, but that's it. 

 


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Jcancom
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johan, thank you for replying; I appreciate that.

Through the years there have been a number of reported patients, though most of them have not been fully published. You mentioned the German liver patient, there is also the melanoma patient. What is interesting is the number of people who have looked at the figure below from the article and missed its meaning. What happened was they treated with 3-BP monotherapy through September 2012 and then gave 3 combination treatments with paracetamol. What is really interesting is how powerfully the combo treatment affected the cancer. The very small rectangle on the right figure on the bottom right is the serum LDH with combo treatment! This result was almost 0! 3-BP can have so much power by itself; when needed there are now a wide range of combinations that can greatly amplify the result.  

There are a number of other patient reports that have been noted over the years. There was a lung cancer patient treated in Columbia with a large response; there were several primary liver patients treated in the US, there was a patient treated in Israel, there was the large German clinic with the tragedy. (What was especially interesting there was that the three fatalities at this clinic have a reasonable chance of being TLS victims (i.e., 3-BP destroyed an overwhelming amount of cancer and these patients might have been treated effectively by liposomal NAC). There have also been many successes with 3-BP at Dayspring (Arizona). Also from D's 3-BP page it is noted that Glab has also reported there own patient success stories.

I am so excited that after all of these years that metabolic therapy is finally on the near term horizon. With one lead metabolic (3-BP) other treatments could be added in that will have powerful synergistic effects. 3-BP and more broadly metabolics could help tens of millions of people coping with cancer. This is such an important step forward! 

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110469/


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johan
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Do you think 3BP harms regular cells? 


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Jcancom
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What has been so remarkable is how minimal the harm to other cells has been under 3-BP treatment. The human patients that have received 3-BP have typically experienced no side-effects. This was reported both for the German patient and the melanoma patient. There is essentially no realization that treatment has even occurred, often these patients have felt better almost immediately. This is in stark contrast to chemotherapy which can have a wide range of difficult side effects.

This near lack of side effects at least at the macroscopic scale probably relates to a number of features of 3-BP treatment. With the mice above, the beta-cyclodextrin formulation is able to deliver much of the active 3-BP treatment directly to the tumors. When the bare 3-BP is used there were a number of serious side effects when used at the treatment dose. Yet, 3-BP itself has a certain cancer specificity as it needs to enter cancer cells through MCT-1 which can be upregulated in cancer cells and the acidic environment of cancer also adds specificity. Cancer cells are highly metabolically active relative to normal cells which also helps to direct 3-BP to cancer cells. Combination treatment can then used to amplify the effects even more by also selectively affecting cancer cells. For example, methylglyoxal is known to have cancer selective effects on cancer OXPHOS.        

While 3-BP might not be a theoretically perfect treatment, at the level of the patient, it has been shown to have profoundly large anti-cancer effects while not inflicting typical side effects from other chemotherapies. What is also reassuring about 3-BP is that an antidote in the form of liposomal NAC and GSH can reverse treatment side effects if given quickly enough after treatment.

   


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johan
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Let's hope it's going to be a fair clinical trial. Btw, you mentioned oncolytic virus treatment, in Japan they have approved one such treatment, DELYTACT, for Glioblastoma. 


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Daniel
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Hi @j @jcancom

We have use this for 1.5 years and while using 3BP and Salinomycin we had our best time. There was no harm from both at the dose we used. There were some temp. and reversible side effects from Salinomycin only but never from 3BP. From 3BP only positive, often feeling more energy after the intravenous 3BP. However, I am aware about the patients in Germany who were feeling less energy, which is a sign that the dose is too high, and it starts affecting normal cells.

Regardless of the treatment, we need to be careful and know what we are doing.

Kind regards,
Daniel


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Jcancom
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D, the headline result is so great! This is close to the CURE! Until now medicine has mostly relied on surgery, radiation and chemotherapy. With any level of metastasis these approaches are largely ineffective. Yet, 3-BP has the potential to introduce another major line of treatment: Metabolics!

We have watched as so many of our forum friends over the years have been overcome by cancer. Without the science of a clinical trial definitive answers about dosing, formulation etc. are unknown. It has been so tragic; it has been so difficult for all of us on forum to cope with this knowledge for all of these years. Hundreds of millions of people have become fatalities since 3-BP's anti-cancer effects were first recognized. 3-BP is possibly one of the most powerful anti-cancer small molecules ever discovered.

It is also very disappointing that the Bracht inquiry never seemed to fully report their results. What were the autopsy results for the victims? What effect did a massive overdose of 3-BP have on their organs? Was it TLS? Not reporting this after all these years feels like a coverup. It would seem that they do not want the truth to be told. That truth being that it probably was TLS. Those patients probably did have truly massive anti-cancer effects; they were experiencing TLS and simple corrective treatment was never offered to them. The Bracht tragedy was a double tragedy because this deeper lesson was never explored further.

Science is fundamentally based upon the premise (assumption) of reductionism. If you keep asking questions, then eventually you will arrive at a comprehensive truth. Yet, after decades of chasing after the inner workings of cancer cells, we do not seem to have reached this comprehensive truth. The problem  is that no comprehensive truth can actually emerge through reductionism with cancer : cancer results from thousands and thousands of mutations. Fixing one variant will then lead the selection of cancer cells without this variant. It is in the very nature of cancer that reductionism is defeated. Knowing even more about the fine details about cancer is that helpful. If Warburg were here today, then he would probably immediately voice the logical error that we have been stuck in.

However, with metabolics this futile reductionism does not occur. Metabolics looks at the macroscopic properties of the cancer environment. Change the lactate production, reduce pH, block glucose uptake, change oxygen levels and cancer cell energy levels. These are all observable features of cancer cells that can be observed. These are the cell properties that metabolics seeks to change. Clearly this approach can have large anti-cancer effects. With 3-BP anti-cancer effects can be seen on imaging rapidly after treatment. Metabolics is more concerned with manipulating what is observable than what is not. If the diagnosis is that the car wouldn't go, typical cancer research would carefully study the  mechanism of the internal combustion engine, the onboard computer systems etc.; metabolics would simply replace the flat tire and then drive away in the car.

As seen above in the cyclo-dextrin study, CD-3-BP treatment removed cancer from some of the mice. It is quite a powerful result. The first treated mice with CD-3-BP appears to have had almost no remaining MCT-1 activity. This mouse did not appear to have any remaining detectable cancer activity. Removing MCT-1 activity would fundamentally change the nature of cancer. It might not be completely a cure; cancer in humans is somewhat more complex than in a syngenic line of lab mice, though the MCT-1 lactate pathway is a major part of the cancer network in cancer. It is one of the major reasons that cancer is such a difficult disease to control. The second CD-3BP mouse above in the figure did have some remaining cancer activity, though what is of interest here is that it also had quite a bit of MCT-1 activity. This mouse could then be treated with yet more metabolics to amplify the monotherapy CD-3BP! The MCT-1 door is still open and this would allow 3-BP to continue to enter and then combinations to add yet more anti-cancer power. Hopefully clinical trials with 3-BP will incorporate this insight into the treatment regimen. Even patients that might not initially respond to 3-BP would still be able to respond with combination amplifiers.

D, this is such big news! We have waited so many years for this and it is finally here. It has been so difficult for all of us and now a new era in cancer treatment is near! Once we have that fist metabolic treatment it will be so easy for others to enhance the effect even more. Yeah!     

     

       

 


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Daniel
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@jcancom Hi J, I agree it's nice to see that a clinical trial is going to start, but as we know its a long way until the end. So, hopefully they will make the right choices in terms of cancer type to be treated first and the administration protocol, so that they achieve good enough results to attract investors. In the worse case, with the first trial we finally have the toxicity in humans established, and that can be used as a reference point for clinics around the world willing to move forward with 3BP.

Kind regards,
Daniel


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johan
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Posted by: @daniel

 In the worse case, with the first trial we finally have the toxicity in humans established, and that can be used as a reference point for clinics around the world willing to move forward with 3BP.

Kind regards,
Daniel

exactly. 

 


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Jcancom
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D, this is so exciting!

The FDA has given the green light for a clinical trial for 3-BP. THE FDA! When people ask "Who thinks that 3-BP should be used in treating cancer?": Answer- THE FDA! Right there that will stop any argument 9 times out of 10. 3-BP has had a problem of name recognition, people aren't sure about it, perhaps all that they know is that there was a problem with it in Germany. Now we have a phase I/IIa clinical trial that has been authorized by THE FDA! YEAH!

Ko Discovery's achieving an FDA IND for 3-BP is very impressive. As the Ko Discovery website notes it is a major accomplishment to be granted an IND especially when it is mostly based on the work of a single researcher. 

One of the other things to consider is that 3-BP is now out there in the field; it is out there where people might have some access to it-- it is somewhat closer to the cancer patients who need it in a formulation that could be very effective. There is a certain potential for a democratic response to occur. For example, perhaps we could consider setting up a GoFundMe for 3-BP. The idea would be that any money raised would be used to find the best biomarker to determine who the responders might be.

We know with certainty that there are large responders to 3-BP. Yvar, likely one of the first humans to receive 3-BP, had a truly massive anti-cancer response. Other early patients also had very large responses. What we could do is raise money to find out which patients might be in the top 1% of 3-BP responders. This possibly could be done in alignment with the company running the trial. Basically, we could fund the patient selection round. Small companies can be resource limited and it would probably be of help to them to have this selection done. At the 1% level there could be very large responses.

I think it would interesting if a 3-BP clinical trial could be conducted for patients who were essentially beyond medical help. People who were essentially on the frontier to the other side. I have thought about what would happen if even one of these patients could be pulled back from the frontier. It would be a miracle. It would be like bringing someone back to life. We know that 3-BP is that powerful. I think that a riot would probably break out if 3-BP could do this. It would be such a powerfully emotional experience. If this occurred, then I think regulators would rapidly lose regulatory control of the situation. People would demand an immediate transition to Right to Try.

D, the situation has become somewhat more fluid now that the FDA has granted 3-BP an IND. We both know how extremely powerful 3-BP is as an anti-cancer treatment. As this knowledge becomes more widely understood this could as they say go viral. There has already been extensive use of 3-BP as noted in a few clinical reports, in the patient reports from Dayspring, in the use in other cancer clinics, and with DIY patients. I suspect now that the IND has been granted more clinics might be interested in treating with it. The momentum is now building for 3-BP and metablics! Yeah!       

There is so much potential with 3-BP. In the notes from Cage Pharma on their upcoming 3-BP trial they noted that they were going to do patient selection based upon FDG. That would be awesome! If you intentionally select patients that will respond to 3-BP then you would presumably be able to guarantee 100% response rates. This is such a powerful aspect of 3-BP treatment that is lacking in other cancer therapy you can rapidly determine who will respond possibly even before the treatment starts. These companies might even be able to offer patients a money back guarantee! Who else in medicine does that? People spend all sorts of money and upwards of years of their time often on treatments that really never show any efficacy. Metabolics could immediately show efficacy. In cells, 3-BP takes effect within minutes! -- Something similar appears to happen in humans treated with it.   

We have been waiting for 20 years for 3-BP to move ahead and now finally it is. This could help so many tens of millions of patients; It could also help to redefine the very nature of cancer. Simply blocking the MCT-1 pathway removes one of the most aggressive manifestations of cancer. In a sense not responding to 3-BP could then even be seen as a good thing. 3-BP finally creates strong constraints on how cancer can behave. After thousands of years of cancer as we know it, 3-BP will create cancer 2.0 which has different metabolic properties which are less harmful to people.

 


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Daniel
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@jcancom HI J, yes you are right, this is a very important step for advancement of 3BP.

Regarding the statement, "it is mostly based on the work of a single researcher." I think and as you know this is based on the work of many scientists, doctors and patients. Of both those who experienced success and those experiencing failure. Even the extremely stupid mistakes made by the German clinic using 10x higher dose contributes to the advancement of 3BP and related knowledge.

I think they already organized a GoFundMe. I am not sure if 3BP has enough exposure to help collect large amounts through GoFundMe. On this line, I also sent an e-mail to dr. Ko to see if we can find a way to help - as you know, MCS Formulas has a Donate program focused on helping to accelerate the transition of academic discoveries to the clinical space. 3BP would clearly fit in to this, but I haven't had a response yet from dr. Ko. So I guess they have enough financial support.

Kind regards,
Daniel


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Jcancom
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Topic starter  

D, yes, my statement could be misinterpreted. I was actually paraphrasing from the Ko Discovery website that was referring specifically to the successful IND approval by the FDA for 3-BP.

D, to have an IND approved by the FDA takes a massive massive amount of work. You have to chop down a whole forest and write an entire library to receive such approval. The FDA requires comprehensive research about every aspect of a drug to be allowed into a clinical trial.  The below quote from the website makes the point more clearly that it is a "rare event" for an FDA approval of an IND by such a "small research entity". It truly is very impressive that a small group could achieve that. I wonder whether a freedom of information request would be allowed to access this IND?

 

"As a result of her thorough research, impeccable work and painstaking preparation she has achieved what could be described as a rare event, by receiving this unique, high level of FDA approval, especially as proposed by a small research entity."

 

I am very interested in what the findings were from the Bracht inquiry. We still do not know! It would seem critically important that these results be published now because 3-BP is going into a clinical trial. If they were intentionally trying to coverup the results, then whatever was trying to be hidden should be revealed so that the knowledge can be used to help others. We really do need to know what happened to those patients. What happened to their organs at high doses? That is very important to know. Did 3-BP cause organ damage? Or was it more that there was TLS? Clearly if it turned out to be TLS that would be a truly enormous story and it would completely change how we understand what happened there. My suspicion is that it was TLS as if it were organ damage one suspects that someone would want to have had that reported. Reporting TLS would not neatly fit the narrative.

There have been so many tens of billions of dollars invested into cancer research; there have been so many hundreds of millions of people who have been fatalities of cancer-- when people realize that we are on the last 100 yard sprint to a highly powerful treatment, then we could see large money flow into 3-BP research.

D, there are just so many people who would want to be onside with this as cancer goes down. I want to be there when cancer goes down. It is almost hard to imagine that I am this close to the biggest story in the history of medicine! Go Jcancom! Go Jcancom! Go Jcancom! Go! Go! Yeah! I am proud of me! If I have helped others faced with the difficult challenge of cancer, then I take that as such a tremendous personal honor.

3-BP is such a powerful treatment that things could really happen fast now. You have a lead metabolic treatment such as 3-BP -- almost anything could have strong combining effect. Perhaps MCS should think of doing something like beta-Cyclodextrin citrate or beta-cycldextrin almost anything. beta-cyclodextrin merely gets a chemical into the tumor space; something such as citrate is probably GRAS.   

I have thought of erg. erg was just so filled with this powerful emotional energy. He spoke about "swearing on his mother's grave". D, just so much raw emotional energy. In my particular culture we don't cry at funerals; we don't have much emotion any time. But someone like erg... it must be so difficult to live with all that emotion. But when we get people like that energized and on our side; when they realize that cancer is pretty much toast -- this could go very large, very fast. How doesn't this result in some sort of riot or even revolution? 3-BP can shut cancer in properly selected patients within minutes. How doesn't that cause social disruption? Even some of the first patients could demonstrate basically complete loss of tumor metabolism rapidly. We know that is possible. The only reason that things probably wouldn't get that interesting is that everything will be phrased in such a cryptic scientific way that people will not even know what just happened. Yet, when the tabloids grab hold of this it will be right up their with aliens invade earth!    

I would find it hard to believe that they would turn down GoFundMe money -- get people on their side! There are always more research questions to ask; it is almost endless. However, with metabolic treatments there are research questions that would have high clinical impact that people could fund that would move the ball upfield. For instance, doing some tumor cell genomics or full genome sequencing of patients could be highly revealing. This would give all cancer patients a biomarker that they could test and perhaps allow them insight how they might respond to 3-BP or other metabolics. There are many many questions and a small biotech company can never have enough money to answer them all.

 


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johan
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@daniel @jcancom

since ammonia is often an issue when tumors break down quickly phenylbutyrate might be a good addition to 3BP.

 


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Daniel
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@j yes, Phenylbutyrate was on top of my list as well back in 2015 when searching for "tools" to address TLS just in case https://www.cancertreatmentsresearch.com/tls/

I had them all at home to make sure we don't have a problem when using 3BP.

Kind regards,
Daniel


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dumbcritic
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@jcancom One company is seeking investment to move it into the clinic https://www.cagephar.ma


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Jcancom
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@dumbcritic, this is super-exciting! We have waited for so many years for this! Without the proper formulation and carefully controlled trials in medical equipped facilities one would have never been able to properly analyze the power of 3-BP.

Yes, Cage pharma also appears to be approaching the starting line for their clinical trial which is another excitement. I think that the CD-3-BP mice trial that I reported above is the formulation that Cage intends to move into phase 1. I am not sure whether Ko Discovery intends to start with 3-BP TACE to the liver.

With a 3-BP product then we could have many powerful cotreatments that could synergize with it.

critic, what is your assessment of 3-BP?


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dumbcritic
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Posted by: @jcancom

Just to note the 3-BP trial will be a Phase I/ II-A. I do not think that I have ever heard of phase I/II before. 3-BP is such a strong product that it should not be entirely unexpected that the phase I/II could be transformed into a phase 3 trial. Even a small phase I study could produce statistically significant results. What are you supposed to say when perhaps all of the terminal liver cancer patients respond within 15 minutes of a 3-BP injection. How many placebo patients will respond in 15 minutes. With careful selection one could imagine being able to choose those patients with super-responder ability based on MCT-1 status. When news breaks that terminal liver cancer patients are responding to 3-BP there could be a near riot out of the treatment hospital. Even in science there can be a certain resignation to letting the will of the people rule.

So a dose escalation to find the recommended phase 2 dose, followed by dose expansion cohort(s) of patients. Depending on the data and interactions with the FDA it's possible that a registration-directed phase 2 (potentially pivotal) trial could happen. Moving it earlier lines, randomised, blinded and placebo controlled trials would be needed.

 

I know Merck is running a phase 3 (KEYNOTE-394) which is comparing Keytruda (an anti-PD-1 mAb) or placebo plus best supportive care in advanced hepatocellular carcinoma patients previously treated with Nexavar (sorafenib). So as a potential second-line treated. Based on the data so far, those given Keytruda had a median overall survival of 14.6 months compared to 13 months for patients given placebo. The percentage of patients who were alive at two years was 34.3% for the former compared to 24.9% for the latter. Keytruda also improved progression-free survival and objective response rates.


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