Anyone used 3bp (3-bromopyruvate)?

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RE: Anyone used 3bp (3-bromopyruvate)?

by JohnnyP on Thu Jan 03, 2019 04:19 PM

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Happy New Year everyone.

Shirley is doing well.  She's still mostly bedridden, but is now able to walk downstairs on her own to go to doctor's appointments.  And her appetite has improved a bit.

Walking.  Reminds me of the death scene in "I remember Mama".  Mama (Irene Dunne) is sitting outside on the front porch of Uncle Chris's house, as he is on his deathbed.  She is reading from his diary, how he gave money for an operation for this child or that child.  Each entry was punctuated with the phrase:  "Walks now".  I say that to Shirley now and then.

We went to our daughter's for Christmas dinner.  A one hour drive each way, plus she sat in her wheel chair for six hours, having a great time.  She only had to go pee once and she used her walker.

At our most recent consultation with her oncologist, we reminded her of Shirley's keto diet.  The oncologist asked if that caused any constipation.  Shirley replied "sometimes", so the doctor wanted to prescribe a pill for that.  I suggested MCT oil, because that can cause diarrhea if you take too much.  She asked "what's MCT?"  I said medium chain triglyceride, made from coconut oil.  She blurted out "give it to her."

I was very disappointed she didn't recognize MCT.  I remembered reading a paper about it earlier this summer as a treatment to prevent or stop cachexia, so I looked it up again:

http://advancedcancerresearchinstitute.com/2015/10/29/clinic

They used a diet of 80% fat, mostly from MCT oil, so I made a shake for her at the time, but forgot it caused diarrhea if you drink too much at once.  As they say, "stuff" happens.  Now we know better, so I just started making shakes again.

My basic recipe for an 8 oz 700 calorie shake:

1 heaping scoop (33g) "VEGA" brand chocolate protein powder

1/2 cup water

1/4 cup coconut cream

1/4 cup (50g) MCT oil

The macros are 85% calories from fat, 12% (22g) from protein, and about 3% (5g) from carbs.  59% of the fat is from MCT oil, as recommended in the paper.

I can drink it, but the stevia taste is too strong for her, so I increased the coconut cream to 1/2 cup.  She also asked me to add some peanut butter, so I added a tablespoon, increasing total carbs to about 10, which is still pretty low.  On her own, she added some coffee and now it tastes really good.  Maybe I can sneak some of the carbs back out of it, hehe.  :)

While she was getting her monthly infusion of Zometa, I asked the scheduling lady if she would forward some emails to our oncologist.  She was glad to do it, so I started with a link to the mercola christofferson slocum video where Dr. Slocum in Turkey shows before and after PET scans of patients under his care.  I may have posted it earlier, but here it is again:

https://www.youtube.com/watch?v=tL8rQ3aNvhs

I called to ask if she had forwarded the material (she had), and while waiting on hold, I listened to all the options.  One of them was the "clinical research department".  I asked about that, and she told me they do clinical trials.  I said they need to see this stuff too!  She said the oncologist will get it to them.

I also sent the MCT cahexia paper.

I sent another one today about 2DG and included this note:

Subject:     Rescue of 2-Deoxyglucose Side Effects by Ketogenic Diet

"Good Morning!!!

More fun stuff for your research staff.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121440/

2DG is a glycolysis inhibitor.  It's a glucose look alike but it can't be metabolized, so tumor cells choke on it.  Normal cells do too, but they can get by very well if ketones are present.  Cancer cells cannot use ketones so the good guys win.

This is part of the treatment protocol used by Dr. Abdul Slocum in his clinic in Turkey.

2DG is not a mystery drug.  Add a radioactive tracer to it and you have FDG-18, used in PET scans.  :)"


RE: Anyone used 3bp (3-bromopyruvate)?

by Jcancom on Fri Jan 04, 2019 02:53 AM

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Happy New Year JohnnyP!

Thank you for welcoming the thread into the New Year! I have been worried about you and your wife! You should have written! A postcard or something? Metabolic treatments have obviously been in motion over the last few months, so I am glad that you touched base again!

I am also glad that you have decided to keep mentally engaged with your treatment team. I suppose the observation that needs to be made is that they are likely all too familiar with exactly what you are talking about. How oblivous can they possibly be? Patient awareness and literacy about treatment options is clearly increasing (This awareness raising is in fact the main rationale for our thread).

{Perhaps the real driver of change will occur when people start voting with their wallets. Specifically, an insurance company or perhaps a consortium of alternative medicine clinics could offer a prepaid cancer treatment package. Considering that the cancer epidemic has now reached the point where everyone is essentially at high risk of cancer during their lifetimes, the clinics could simply allow people to pay ahead for what is now becoming almost inevitable.}  

However, the current system really is not designed nor is it intended that front line workers actually attempt to innovate treatment. These oncology workers likely wind up with a range of mental health problems as a result. Essentially they are stuck in a pathological system that prevents all innovation (even when it is clearly evident that such innovation would benefit patients as mentioned in the video link you provided): the health care workers are then yet more victims of the health care system. I can certainly imagine how people could get stuck in a job such as that, though from where I am now, I would decline a hypothetical million dollars a year to treat patients with treatments that I had no belief in.

BIG news on D's forum. Our homespun metabolic protocol is starting to generate some notable successes! We have been trying for years to reverse engineer a metabolic treatment; now we are finally hitting some traction.

The big insight that we stumbled over was metabolic metronomic dosing. D started this off with his foundation using metronomic 2-DG and ketogenic diet/fasting (fasting can be thought of as a type of metronomic metabolic intervention).

Over the last few months patients are trying this out and it looks like it is truly benefiting them! We are moving on now to a second generation version of this by adding in other metronomic metabolics (such as Vitamin C, methylglyoxal, etc.). It is not clear yet how the second generation treatment will work out, though there is increasing excitement about what has already been demonstrated.

Johnny, you threw D some green for this idea, so it might be worthwhile to consider integrating this into your wife's treatment. The successes so far on the forum have been with people that have what can clearly be called metabolic cancers. Yet, the video showed a fair number of examples of breast cancers that responded to metabolic intervention, so it might be helpful. You could integrate the metabolic elements into metabolic chemo as was done in the video. This way you could stay with your current team, and yet add in some elements on the side with their help. The protocol that is evolving on D's site is similar to what is being done in the Turkish clinic. 

Another one of our insights is that treatment should become a continuous part of the patient's life. You noted monthly Zometa. With the metronomic metabolic approach that is evolving on the forum, treatment is around the clock. This largely avoids the consequences of maximal dosing leading to drug holidays and then rapid tumor progression. One of the charts on D's forum shows what happened during such a drug holiday: The tumor markers went Vertical! Patients on maximal dosing schemes become addicted to chemo. As soon as they stop taking treatment to recover from side effects etc., their tumor growth becomes rapid. With the new metronomic approach all the treatments need to be well tolerated because people would not be able to stand a treatment that could last for days if it weren't. Bascially gentle treatments are a natural consequence of being adminstrered continuously. This constant gentle breeze, counterintuitively, appears to be more effective than intermittent harsh gales.

Another recent post on D's forum might be of interest to you. Research used microneedles to inject honokiol into the breast using a carrier oil. D was very impressed when he realized that this increased the uptake of HK by about 70 fold!

Best Wishes, JohnnyP! I greatly wish that you will find some of the posts here or on the D's forum to be useful. As you are clearly aware now, one must do their homework!

  

RE: Anyone used 3bp (3-bromopyruvate)?

by dumbcritic on Fri Jan 04, 2019 08:35 PM

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Bristol-Myers Squibb buys US rival Celgene in a major deal. I just hope the dreaded 'portfolio rationalisation' doesn't come into play as this could mean the end for many therapies like JCART17 and bb2121 to name a few. There are others too [1,2]

In other news RP3 has been finalised [3] and a Sanofi moves forward with I.T. administered mRNAs [4]. Moderna is working on the latter and currently have three (OX40L, OX40L+IL-23+IL-36y & IL-12).

Refs:

1 https://www.fiercebiotech.com/biotech/celgene-expand-dragonf

2 https://globenewswire.com/news-release/2016/07/19/857040/0/e

3 https://ir.replimune.com/news-releases/news-release-details/

4 https://www.fiercebiotech.com/biotech/sanofi-invests-eu80m-b

RE: Anyone used 3bp (3-bromopyruvate)?

by dumbcritic on Fri Jan 04, 2019 10:07 PM

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On Dec 06, 2018 3:55 AM Jcancom wrote:

Good one critic!

There is even more of an international 3-BP collaboration happening than I had realized. They talked of a private 3-BP conference in Brussels. Why wasn't the thread invited?

Yes, I had wondered about the Yeast article as well, what did they mean by a "wash". Sort of dab on it onto the melanoma? I would want a more thorough description as I am not entirely sure that dabbing would be safe. With a melanoma tumor I thought they meant it more as an IT injection. Do they really mean to just "wash" it onto the skin? The sequence of photos for that figure are quite impressive. I would also be interested in knowing more about this patient's experience.

This article has several points of note. 3-BP is positioned as an anticancer therapy that could control metastasis. The article proposes this as almost a unique property of 3-BP. I am greatly anxious to see how they might develop the idea that 3-BP "results in a dramatic increase" in apoptosis after prolonged exposure though not after only 4 hours. They also hinted at an article about P450 in preparation. Would be a great gift for the season!

The article quoted the 2012 WHO cancer statistics which noted mortality of 8.2 million. Shockingly the recent Globocan estimate for 2018 is a global cancer mortality of 9.6 million. We are within months of hitting an annual global cancer mortality level of 10 million! Something needs to be done!

This is what failure looks like! Hitting 8 figures should be telling us something: Specifically, we are doing something wrong. We need more innovation: We need a more flexible regulatory environment: We need patients that are more aware of the past results of therapies (e.g., chemotherapies) and explore other options: We need greater freedom of Right to Try for patients.

https://www.iarc.fr/featured-news/latest-global-cancer-data- cancer-burden-rises-to-18-1-million-new-cases-and-9-6-million-cancer-deaths-in-2018/"" target="_blank" rel="nofollow">https://www.iarc.fr/featured-news/latest-global-cancer-data- target="_blank" rel="nofollow">https://www.iarc.fr/featured-news/latest-global-cancer-data-

After reading it again, it seems 3-BP was applied topically. Without a published case report it's hard to know if the patient suffered from any side-effects or not. Either way I agree with you and this looked impressive.

We know from previous preclinical studies that IV 3-BP can eliminate metastases [1]. As I've said before, I think the right setting to test this would be in patients with resectable or borderline resectable pancreatic ductal carcinoma who are unable to have FOLFIRINOX. The hope would be that this increase survival. If it does, then testing it with a vaccine could be another option [2].

As for Right-to-Try a number of improvements are needed. The same goes for certain regulations [3].

Refs:

1 http://cancerres.aacrjournals.org/content/62/14/3909.long

2 http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.411

3 https://srconstantin.wordpress.com/2015/12/06/regulatory-pro

RE: Anyone used 3bp (3-bromopyruvate)?

by JohnnyP on Fri Jan 04, 2019 11:35 PM

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J:

This is the clinic we are using:

http://www.pacificcancermedicalcenter.net/index.php

Shirley's oncologist is pictured on the home page.

I was very surprised when she asked "What is MCT oil".

I spoke to her younger colleage on the phone once about Shirley's diet.  She said "Keto is only good for losing weight, it's not for cancer.  Your brain needs glucose."

I said to her "Are you aware of Dr. George Cahill's research in the 60's where he starved patients for forty days?  Their brains were running on 66% ketones."

She replied "I have to get back to work."

I understand it's hard for them to keep up on their reading, that's why WE are doing it and sending them the good finds.

RE: Anyone used 3bp (3-bromopyruvate)?

by Jcancom on Sun Jan 06, 2019 11:34 PM

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JohnnyP, it's great that you're back! Things are actualy getting quite exciting around here. Well perhaps not so much here as over at D's! 

We finally might have something that will meaningfully help people!

Metronomics is the key. Consistently doing something that has therapeutic benefit can have profound of anti-cancer effects. We can now synthesize a substantial amount of the cancer research literature including Vitamin C, various vegetarian type diets, fasting, etc. as at their core being metronomic metabolic treatments. I suppose that there are other successful treatments out there, though my guess now is that most if not all cancer miracle type stories that are reported could after careful consideration be categorized as metronomic metabolic approaches. 

The prototype for our current understanding arose from a patient with pancreatic cancer. Applying a metronomic metabolic treatment has resulted in the last few months in a near complete collapse in CA 19-9 levels. During August and September, the CA 19-9 values decreased by an ORDER of MAGNITUIDE per month! At last labs they were still falling.

It is true that this patient is also being treated with low dose chemo, so some might say, "Well it's the chemo!". Apparently even the oncologist did not believe this; they are seeking advice from D's foundation on how to help their other patients. Basically continusously apply metabolic stress along with chemo and the tumor totally collapses. I would think that those who truly knew what they were doing would not even need the chemo! It might take us a while to get to that point. 

I can certainly see why the clinic in the video you posted that treated with a similar metabolic approach had impressive results. While patients were in a clinic type environment under such a treatment protocol, rapid tumor collapse probably should be expected to be the norm. The problem as was noted is that as soon as patients leave the clinic they will start snacking on cookies etc.. (with our current approach that would not be as big of a concern).

Pancreatic cancer appears to have several features that make it especially notable as a metabolic cancer (highly hypoxic/glycolytic/low nutrient, desmoplasic,etc.). No great surprise either that Prescience was considering bringing 3-BP to the clinic as a treatment for pancreatic cancer. Given this perspective it is difficult to understand why the prognosis for these patients has not greatly changed with this new understanding.    

The basic lesson from pancreatic cancer can then apply more broadly to many other cancers. Dayspring has reported success in most major cancer types. However, I am still somewhat unclear whether the metabolic approach will in fact be universally helpful in essentially all patients. 

I think what brought us to this point was that on D's forum there were patients who were earlier stage, and others who were still responding to chemotherapy etc.. We could then watch to see what helped them. One big eye opener was that it really is more about finding a treatment that will have a net positive effect day in and day out over the course of months. You can always bring out the heavy hitters like 3-BP, though even something such as Eat your Vegetables through time does appear to help.

This was our first successful big idea: Continuous (metronomic) treatment. Even metabolics can be seen to have only a limited cancer effect if treatment is only sporadic. 

There are many many possible effective treatments if they could be applied essentially around the clock. 

This reminds me of the article that you cited. That article noted that over 1,000 cancer patients have been reported to have went into remission through glucose restriction. The approach suggested in the article has been criticized on thread for being extreme, dangerous and unrealistic which to some degree is true, though the basic concept of fasting (when possible), possibly ketogenic diet etc. clearly is not without a scientific foundation.

https://arxiv.org/pdf/1407.7622.pdf

I am not sure whether you are aware, though an update of the above hypothetical treatment has been published. 

https://ac.els-cdn.com/S0306987718303840/1-s2.0-S03069877183

Interestingly, this protocol has already been applied to non-cancer patients. So, it is not as hypothetical as the first report.

The treatment that they are proposing is:

lead in with ketogenic diet, then

1. propanolol and oxygen
2. somatostatin, propranolol,and  phentoalamine
3. insulin

This is expected to give 2 mmol Glucose (36 mg/dL).

The first artitcle noted that in non-ketoadapted individuals even 40-49 mg/dL can result in coma. Yet, it goes on to speak of those who hunger striked for over a year who went down to 20-30 mg/dL without apparent harm. It is quite startling that the above protocol might mimic year long starvation, without the year long starvation part.

Another idea that we have brought into the treatment is to have a variety of metabolic blockers. We have seen that even with something as powerful as 3-BP resistance can and does occur. Yet, if you load up with a range of glycolysis and OXPHOS inhibitors this risk should diminsih. We will still need to watch out for this, though.

The latest exciting idea that is percolating is perhaps including metonomic chemo. Up till now we have been focused on metronomic metabolic. Yet, metronomic chemo could amplify the success we have had with metronomic metabolic. What seems to happen is that metabolic chemo primarily works through changing the tumor vasculature. One article showed how the tumor became almost entirely perfused during metro chemo. Bringing in oxygen and nutrients to the tumor presents a wide range of opportunities to further metabolically stress the tumor mass (also the chemo switch strategy).    

Lots and lots of excitement!

So much to read and try and understand. For example, serine deprivation, glucogenic/ketogenic amino acids, effect of exercise of acid levels etc etc.

JohnnyP, there is a very large amount of thinking and homework to be done! I realize that it is simply a ridiculous burden for a person coping with a loved one with cancer. What I can tell you is that you are almost certainly on the right track. Metabolic thinking is very close to the answer; metronomic metabolic thinking puts you almost directly on top of it. 

Once you can jump that first hurdle you are off to the races.

One of the bigger hurdles to get over is the routine of your life up to this point. Think of how you live now as being part of the cause of the problem and then create a lifestyle that is orthogonal. This is exactly what cancer clinics offer their patients: Lots of vegetables, probably somewhat restricted calories etc..

Best Wishes and Good Luck!     

RE: Anyone used 3bp (3-bromopyruvate)?

by JohnnyP on Mon Jan 07, 2019 01:48 PM

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J:

Google couldn't find a link to a free version of the full article.  :(

Orthoganol?  How about 180°?  :)

Shirley used to live on toast and jam for breakfast, and high carb foods every meal.

Before her diagnosis, she was spending more and more time in bed, so I took on the job of cooking.  One of our favorite things (quick, easy, and cheap) was stacks of pancakes or waffles, syrup for me, jam for her.  I was killing both of us.

After her diagnosis, I learned I was pre-diabetic, so mostly carnivore diet for me, with occasional avocados, cauliflower, broccoli, and blackberries, is about it for me.  My glucose reading is usually about 105, very rare to get below 100.  My ketones average about 0.8.

Shirley's glucose is usally about 95 or so, ketones about 2.2.  She wanted toast and jam this morning, so I gave her 17g of toast and half a teaspoon of marmalade.  A couple hours later, her glucose was 115 and ketones were 1.8.  Not as bad as I thought it would be, but the cancer said thank you for the snack.

She just doesn't believe me that toast is as bad as candy.  Candy is sweeter, so toast can't be that bad, is her thinking.

It's a struggle.  Food is about all she has to look forward to, and she doesn't eat much even then, but she is doing her part to stay under 20g per day, just wish they were low glycemic carbs.

We watch a lot of low carb videos together, mostly the shorter ones, by Dr. Berg, Dr. Ken Berry, Jason Fung, etc.  Now, when we see someone that has become overweight, she says look at the damage carbs have done.

RE: Anyone used 3bp (3-bromopyruvate)?

by JohnnyP on Tue Jan 08, 2019 12:19 AM

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I notice there are only five comments to the Mercola Christofferson Slocum video I posted above, one of which is mine:

(From)

J&S Electronics3 days ago

Dr. Mercola, Travis: Have you tried reaching out to celebrities and ranking politicians that are dying from cancer? John McCain would have been one. Now I hear Olivia Newton John is nearing the end. Save just one of the rich and famous and the cancer world will learn about these life saving protocols."

We need to get this message to Mercola and Christofferson.  One wealthy survivor could fund a small trial.  I think I read that Dr. Ko was only looking for $3M for 3BP?

RE: Anyone used 3bp (3-bromopyruvate)?

by Jcancom on Tue Jan 08, 2019 01:34 AM

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JohnnyP, get off the couch!

With cancer it is important to Go Go Go 24/7! Some of the patients on D's forum appear to be receiving treatments around the clock! From what I can see from their efforts and the impressive results that they are achieving, this might be necessary (at least until we have a much better idea of what we are doing).

You need to be constantly thinking: What am I doing right now that will push down the cancer. On D's site they appear to have the vitamin C/2-DG etc. ivs flowing at all times. These metronomic metabolic approaches simply wear down the cancer! It finally just gives up! That is what our interpretation is now and in the meantime we will be actively searching for yet other treatments to add on if they are found to be needed. 

A great part about this recent insight is that we can stop arguing among ourselves on the forum. With a fair number of metabolic treatments, there is a large amount of disbelief whether they would actually be effective. I really did not want to commit myself on vitamin C or citrate or a wide range of other proposed treatments because they did seem on the surface to perhaps be flaky. However, now that metronomic metabolics has been revealed to us, there is no longer really anything worth arguing about. Any metronomic metabolic treatment approach should have high credibility even on first encounter. 

D's forum had a multi-year brawl questioning the anti-cancer potential of citrate. Why argue about this? A cancer researcher who apparently had successfully treated many patients with a citrate based treatment protocol was repeatedly disparged for his ideas on forum. Yet, it is widely known that citrate/citric acid inhibits PFK. A metronomic treatment using this approach should have significant anti-cancer effects. 

This is exciting! A wide range of metabolic treatments can be seen as essentially being metabollically equivalent and we will be able to discuss the science now united and not divided.

The second article I cited is yet another metabolic approach that has significant potential. Under Right to Try, this treatment already has potential for clinical translation. Moving down to 35 mg/dL glucose without prolonged starvation opens this up to a wide range of patients. I would certainly wonder what would happen if this were done metronomically. I am also interested in how adding in other glycolytic and OXPHOS inhibitiors might amplify the effect.

I am (was) quite confused that your wife continues to have such high glucose levels after such prolonged fasting and weight loss. I do not quite understand that. I did search today for the essential amino acids online today: You could buy all of them individually. There is some research that speaks of amino acid therapy, so it might be worth a try. My guess at this time is that controlling the intake of gluogenic amino acids ( in particular the non-essential ones) might reduce the glucose levels though I am not sure about this.

Such an enormous amount of interesting research to read through. I have been reading about the cell cycle and its relation to the circadian cycle among many other topics. Finding a way to integrate this into the metabolic approach could further amplify the treatment effect.What if we could stop most of the cancer cells at G2 and then apply metabolic blockers? S is a high ATP consuming phase, so it might be worth a try. 

JohnnyP, time to get into gear! There are so many things that you should be trying! Get going!

RE: Anyone used 3bp (3-bromopyruvate)?

by JohnnyP on Tue Jan 08, 2019 07:51 PM

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J:

I mentioned metformin to one of her doctors, he said it's not proven safe for cancer patients.  I mentioned 20mg/kg body weight is way below the max safe dose, he said it doesn't matter that it's proven safe for diabetics, who knows what kind of side effects there might be.

Hmm, I wonder what he would do if he had a patient with both cancer and diabetes.  His head might explode.

So, now she's afraid to take metformin even if I were to get a prescription for my pre-diabetes.

I found two papers on nanocurcumin:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509453/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868037/

I ordered some but she is afraid to take it.  Naturally, she wants to run it by her doctor first, now that he has her scared of things not from him.

J, I know you are trying to help, but we can't go into the clinic and say "let's get going with this 2DG stuff I heard about."  Even Keto is foreign to  them.  They still have a bowl of candy in the infusion room.

The infusion lady had trouble finding a vein and hurt her very badly this last time, leaving a two inch square bruise on her wrist.  She said that's the last time they hurt me.  She is ready to bail on her Zometa.  It's once a month for twelve months, seven more to go, I think.  Then once every three months, but she doesn't want it.

Even if I had a list of over the counter supplements to try, it would be hard getting her to take them.  The few pills she takes now are all she can stand, plus she would want an ok from her doctors.

Are you asking me to set up a home lab and start doing IV's of experimental drugs?  I don't think that will fly with her even if I could buy 2DG, etc.  That stuff can kill you if your ketones are not high enough.

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