Following our discussion on Cancer Compass, Dr. Jason shared with usrelevant information related to 3BP treatments and next to that some more info on Salinomycin and new treatments he is currently using with very good results.
Jason R. Williams, MD is a board certified Radiologist who specializes in the diagnosis of conditions using imaging technology. With such technology, he can deliver treatments locally via methods such as TACE. He was part of the team who at the end of last year made the news around the world with a great success. Using Salinomycin and 3BP, during one month, the team succeeded to cure a stage IV lung cancer patient who was not responding to conventional methods.
I am not allowed to share the documents I have received from Dr. Jasonbut I am allowed to share a summary of that:
1. Various doses and preparation methods have been considered in order to obtain stable 3BP solutions. In general, the dose used is in the same range as the one we know from the various publications, i.e. around 2 mg/kg. I only saw results from administration via TACE. From the formulation point of view, the most relevant aspect to me is the fact that in order to obtain a more stable solution, 3BP has to be first mixed with water for injection. This mixture can than be inserted in the NaCl bag (I will address the how in more details in the 3BP page of my blog so that you have a clear view on where this fits into the preparation method, if that is not clear now). Indeed, I know that the 3BP prepared in Egypt as delivered to the melanoma patient used the same technique, but somehow I did forgot about it and was not aware about its strong impact on the stability… Note: for your reference, if 3BP is mixed with water (e.g. 500mg in 10ml) will be stable for a month or more (if stored at 4C).
2.Dr. Ko’s biggest concern is that people will use to the wrong way and give it a bad name.
3. For the use of 3BP patient selection and administration is key. This is because from what Dr. Jason learned, in some cases there is resistance developed to 3BP and that the tumor will return more aggressive. Similar to the results from chemotherapy. This is why Dr. Jasonthinks “debulking (ie surgery or ablation) would be useful. The lower the tumor burden, the better chance that 3-BP can completely eliminate a tumor. Larger tumors do not get enough 3-BP to provide adequate tumor killing before it will mutate (become resistant) and resurge.”
Indeed, he shared with me pictures showing cases where tumor became more aggressive after the treatment with 3BP. This is an important reference point for us. Until now, we have severalexamples of people doing better with the 3BP treatment and knowing that is possible to also go the wrong way is important. As a result we have to think and try design treatment protocols that would reduce such risks. At the end of this post I will discuss how I think we may be able to reduce these risks.
4. Dr. Jason also thinks “Smaller tumor (pancreas, pelvis and sacrum) seemed to respond fully”
5. Dr. Jason will connect me with people that have been treated with 3BP and are alive
6. Due to the risks Dr. Jason has identified related to the 3BP treatment, he prefers to useintra-tumoral immunotherapy and ablation, as the success rate is much higher, looks like >80%. This sounds very interesting and I will ask more questions about this treatment route. I even intendto havea page dedicated to that if Dr. Jason will supply enough info.
7. Some relevant information related to Salinomycin treatment schedule has been shared as well: I will implement this on the Salinomycin page I intend to build soon but the most relevant point here is that there are various places in theworld where patients are treated with Salinomycin and where the treatment cycle include 5days treatment / week and 4 consecutive weeks. From my personal experience I think this may depend on the patient response and if the response is great lower treatment frequency may be required. Note that the published report where Salinomycin was used on humans at Heidelberg 2012, teh treatment cycle was during 24 days, one day on and one off. Again, to me Salinomycin is the most effective treatments I have seen so far. That is all about Salinomycin. Valium and Propranolol may be used for pre treatment before Sal treatment – I have to check this one.
9. Results seems to be better when combining Sal with 3BP compared to when using single substances for treatment.
10. Received a very interesting article on the lactate transport. I will study and come back with conclusion:http://www.ncbi.nlm.nih.gov/pubmed/24928781
11. Dr. Jason thinks “there are still uses for 3BP and hopefully with the right combo, it can be even better”
12. On the future of 3BP: “Patent issues and analogs make developmentchallenging”
After all the above my questions are:
– Was paracetamol or any other technique to reduce glutathione used? This may be able to counteract the resistance if there is no change in metabolism.
– Was there a PET/CT scan performed after tumors became more aggressive? If yes were they more active on PET or become invisible on PET? This is very important since the tumor metabolism may be changed. If yes, which I believe is the case, we can come up with strategies to stop those as well.
– The patients were treated only at the clinic or they also had continuous treatment at home?
My conclusion from all input from Dr. Jason is as also suggested by Dayspring Clinic: in some cases 3BP is effective in affecting tumors that may not be anymore responsive to mainstream medicine. However 3BP treatment is an art and to make the best out of 3BP treatment we need to support 3BP. And we need to learn more on how to do that.
For now I wish to thank Dr. Jason for his kindness in sharing important information with us. Based on the info I have received and e-mail exchange with other people it is clear that he is focused on getting the best outcome for his patients.
Ok, so what we get from Dr. Jason is that tumors that only partially respond to 3BP may stop their responsiveness and start growing again. I can imagine that as well, based on what I understand so far. But based on the same, I can also imagine ways to counteract that trend when that happens, while I do think this will only happen in limited cases. So here is what is in my mind for now:
As we have learned, 3BP will work against cells that have MCT1 transporters activated. There is literature available (reference to be added) suggesting that MCT1 cells may only be present at the surface of the tumors in case of large tumors (small tumors may all consist of MCT1 expressing cells). The MCT1 expressing cells will be there where they have access to oxygen and lactate/lactic acid (i.e. in an acidic environment). Once you kill those you are going to be left with cells that are using glucose only and not lactate. These may be the cells who are observed by dr. Jason as growing back fast since those relying on glutamine are usually slower in development (reference needed). If that is the case, then we can have severalmain strategies against them:
1. Anti angiogenesis inhibitors:those cells thatsurvive, in order to proliferate they will need to build a structure of veins through angiogenesis. That means that using angiogenesis inhibitors together with 3BP will help.
Here is a list of angiogenesis inhibitors known to have anti-cancer effects: Thalidomide, Albendazole, Captopril, Celecoxib,Myo-InositolTrisPyroPhosphate,Shark Cartilage,Bee venom,Sa-mi-yeon-geon-tang. Most of them are known to have strong anti-cancer effects alone and I will discuss them separately in this blog (including the dosage and sources).
2. Proton transport inhibitors: this is an impressive strategy specifically addressed by Prof. Salvador Harguyndei. Using this strategy alone, this great professor and oncologist from Spain has succeeded to cure a good number of his patients including pancreatic cancer, breast cancer and ovarian cancer. This strategy will be specifically addressed on my blog as I think is one of the great anti cancer strategies. The idea is simple and will be very effective against highly glycolytic cells that may not be sensitive to 3BP: during glycolysis cancer cells will produce a lot of protons. This will acidify the intracellular space. This is not what cancer cells like since they prefer a high pH (they are more alkaline than normal cells). By inhibiting the transport of protons out of the cancer cells the intarcellular acidity will increase and that in turn will kill the cancer cells. To this strategy you can add local hyperthermia that will help to further lower the intracellular pH.
3. Glycolisis inhibitors: to be discussed but simple inhibitors are 2DG
4. M2 macrophage inhibitors: seehttp://www.sciencedaily.com/releases/2015/08/150812200529.htm
5. Microtubule dynamics inhibitors:Mebendazole, Griseofulvin or Noscapine
6.PDK1 inhibitors such as DCA (Dichloroacetate ) or ALA (Alpha Lipoic Acid)
Received answer from Dr. Williams to my questions above. Here is the summary:
1. They were also continuously in the search for a more stable formulation that would be more effective.
2. They have used Paracetamol but lower dose compared to that used in Egypt case.
3. Those tumors that have evolved after 3BP treatment were even more visible on PET scan (as I expected based on the mechanism I imagine). This is good because so far we (think) understand what is happening:
– one option is that simply the formulation used was not the best
– the other option is that the formulation was effective but what was left there were the cells functioning on glycolisis only.
There are strategies to stop those or to convert them again into 3BP responding cells. A little repeating the above but with a bit different angle:
1. To stop the cells based on glycolisis we can:
– use proton transport inhibitors (see above)
– use glycolisis inhibitors (see above)
– used PDK1 inhibitors such as DCA (Dichloroacetate ) or ALA (Alpha Lipoic Acid)
– Salinomycin may do the job as well while not only fucused on glycolisis due to its mechanism of action
– they are fast deviding cells so they need Iron to duplicate: use Artemisin, high dose Vitamin C
– they are fast dividing cells so microtubule dynamics inhibitors such as Mebendazole, Griseofulvin or Noscapine will help
2. To convert the cells into MCT1 expressing cells:
– they need Oxygen for respiration so put Oxygen into the body:Myo-InositolTrisPyroPhosphate, Hydrogen Peroxide, EWOT, etc.
– they need PDH so use DCA (Dichloroacetate ) or ALA (Alpha Lipoic Acid)
– they need acidity so don’t use high dose alkaline treatments such as NaBic
– use Sodium Butyrate that will enhance MCTs expression including MCT1
In case the cells have MCT1 but still not responding we need to:
1. Use Gluthadiole inhibitors: Paracetamol
2. Make sure the 3BP solution is effective: use various formulations (there is a debate on what is the best buffer and weather there should be used any)
3.Make sure 3BP is getting to the tumor: use various administration routes and add Nitroglicerine or B3 (Niancin) vitamin to open up the veins
4. Make sure you do not use MCT1 antagonists: e.g. Quercetin, Ibuprofen, Statins, etc. (will be discussed on the 3BP page)
Ideas, comments, suggestions on the above are always welcome! So please comment 🙂