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3-BP Imaging study Good one!  


Jcancom
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I am not sure how we missed this article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337871/ but it is a good one. It shows that even after 2 hours the metabolic effects of 3-BP can be discerned by FDG PET imaging.

{Am I the only one that is not overly impressed with the new web interface for pubmed? Typically upgrading website interfaces does not add value. It might seem dull, but if a site is working don't try to redecorate for the fun of it. With pubmed now there does not appear to be an easy way to scroll through the pages as there was before. They worked so hard on the upgrade ... and they made it worse!} 

The 3-BP article is exciting! If the same imaging were done with human patients, then the 3-BP conversation could rapidly change. 2 hours to a response? There are probably a great many patients who would be interested in that.The endless discussions questioning the possible efficacy of 3-BP could quickly be brought to an end, with a few dramatic 3-BP response.

What is especially important to recognize is that it is not even necessarily only about the response, but the illness timeline. Many treatments can take months and months to have a demonstrable response as evidenced by biomarkers etc. Even within 2 hours 3-BP could be evaluated for success; if success were not achieved then you could then move onto something else. This is one flaw in modern clinical trials, they do not add this aspect to the determination of efficacy. All clinical trials currently do is follow patients without regards to the opportunity cost of time involved in treatment.  I great wish that when the 3-BP clinical trials start that they will include imaging to demonstrate patient response and even more powerfully for patient selection. 

 


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NA
 NA
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Hey Jcancom! How are you? Any news on when the 3BP clinical trials start?


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dng050
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The potential of 3BP seems very promising. But I have not seen any stories of complete remission, not even from clinics which supposedly are experienced in giving this treatment, such as the Daysprign Cancer Clinic.

Is there any recent updates on 3BP which can afford us more hope?


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dng050
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Manuone
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J! Glad to read you again! You have come back with force with one of your favorite molecules such as 3 bp!
It sounds interesting because observing a "fast" efficacy would avoid subjecting the patient to treatments with no effectiveness.
I have some topics to discuss that I will be publishing step by step! 🙂


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Jcancom
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Johan, we need more mystical light!

I am okish. Just not 100%. I have never not been 100% in my life. It is frustrating. We have been making great progress on the forum over the last year or two, I really want to see us move it up a notch.

There seem to be clinical trials popping up everywhere for 3-BP on the horizon now. This is a very exciting time for 3-BP clinical development. If there were to be FDG PET prescreening and then monitoring for response, then things could become quite interesting. It is quite frustrating that after all of these years there are people that can still question the basic premise of 3-BP treatment. It would not take too many  PET scans that showed rapid cessation of FDG imaging to stop the argument.  

I tried to move the photo from the article into this post though the software wouldn't let me. I attached it below. Take a look! The 3-BP treated animals no longer have bright yellow tumor activity after 2 hours post-treatment!


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Daniel
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Posted by: @jcancom

I am not sure how we missed this article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337871/ but it is a good one. It shows that even after 2 hours the metabolic effects of 3-BP can be discerned by FDG PET imaging.

{Am I the only one that is not overly impressed with the new web interface for pubmed? Typically upgrading website interfaces does not add value. It might seem dull, but if a site is working don't try to redecorate for the fun of it. With pubmed now there does not appear to be an easy way to scroll through the pages as there was before. They worked so hard on the upgrade ... and they made it worse!} 

The 3-BP article is exciting! If the same imaging were done with human patients, then the 3-BP conversation could rapidly change. 2 hours to a response? There are probably a great many patients who would be interested in that.The endless discussions questioning the possible efficacy of 3-BP could quickly be brought to an end, with a few dramatic 3-BP response.

What is especially important to recognize is that it is not even necessarily only about the response, but the illness timeline. Many treatments can take months and months to have a demonstrable response as evidenced by biomarkers etc. Even within 2 hours 3-BP could be evaluated for success; if success were not achieved then you could then move onto something else. This is one flaw in modern clinical trials, they do not add this aspect to the determination of efficacy. All clinical trials currently do is follow patients without regards to the opportunity cost of time involved in treatment.  I great wish that when the 3-BP clinical trials start that they will include imaging to demonstrate patient response and even more powerfully for patient selection. 

 

J, its very nice to hear from you again. Did we miss this one even in cancer compass discussions?

 

I think there is one very important point that these results highlight:

3BP can induce tumour necrosis and can do that fast.

This is extremely important information that can help us to design a successful clinical trial, and if we do not take it into account will lead to a complete failure with tumors growing faster than before.

To clarify my point:

3BP can be essentially implemented in two different ways:

1. intra-arterial (or released at the tumor location)

2. intravenous (systemic)

 

1) When 3BP is administered at the tumor location, this will produce necrosis (assuming that the tumor is well perused and the micro-circulation functions). There are two potential outcomes in this case:

a) the tumor well addressed and 3BP induced complete necrosis - GREAT outcome - more likely in animal studies

b) the tumor is large and not completely destroyed  - outcome worse than without 3BP treatment - more likely in humans

The outcome will be worse in the second case because, necrosis will be perceived by the body as a wound. In this case, immediately after that, an inflammatory reaction is initiated and fibroblasts are deployed at the tumor location that will become part of the tumor micro-system. That means, that in a matter of days, the tumor can be seen on CT larger (due to the fibroblast and others). And these fibroblasts will further deliver the nutrients required for the tumor to grow even better than before.

All this is not theory - it has been observed on CT in humans.

This can happen not only with 3BP, but with all treatments that trigger strong necrosis while not doing the job completely.

So what can we do to avoid the kick back of the tumor in this case?

- One option is to maintain the treatment until the tumor is completely destroyed - that can not be done easily with trans-arterial chemo embolisation, unless a metronomic approach can be found

- The other option is to inhibit the strong reaction of the human-body to necrosis (inflamation-related events including fibroblast activity). That could be achieved with strong anti-inflammatory (glycolisis inhibitors) given immediately after the treatment (3BP in this case) that induces partial necrosis. One such a treatment that can be implemented immediately is Phlorezin or 2DG metronomic (both discussed on this website in separated posts).

2) The other way we can use 3BP is intravenous (systemic treatment) - this treatment may lead to some tumor regression (we've seen about 17% after the first month of use), not very strong, but maybe most important will "clean" the blood of circulating tumor cells and help reduce the chance of metastasis.

In conclusion:

- If 3BP is applied at the tumor location, to maintain its effectiveness it needs the support of strong anti-inflammatory options.

- If applied intravenously may help extend life of cancer patients by avoiding (further) metastatsis. We used 3BP for long time in this way and we did saw good benefits.

Finally, soon (in a few days) we will launch the supplement company and I will have time again to allocate to our nice discussions here and address new treatment options. So I am happy to see you back J, and hope to see you more often again as it is always a pleasure 😉

Kind regards,
Daniel

 

 

 

 

 

 

 


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Jcancom
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dng050, you are right that it has been quite disappointing that over 20 years there has been so little clinical advance with 3-BP. 3-BP has such large potential and yet for some reason it never seemed to interest the pharmaceutical industry. It would be so helpful if they were to do a full workup with 3-BP and find the best possible chemical and the best possible formulation. This might never happen.

Nevertheless, there has been a large amount of 3-BP pre-clinical research; possibly the most for a cancer drug that has never even started a clinical trial.

The 3-BRoP formulation is of particular note. By simply adding a few carbons on the end of 3-BP, an enhancement appeared to occur.

There is also the POH-3-BP combination. That is quite exciting! The research suggested that they could simply move 3-BP into cells without respect to MCT-1 expression. That would be stunning if they could show this in human clinical trials. The only barrier at this time is actually for 3-BP to selectively gain entry into cancer cells. Once 3-BP is inside it attacks almost everything. I very much would like to see more research about POH-3BP.

There is also the research using ethyl bromopyruvate. Roughly 3-BP in a pro-drug formulation. Some patients have been injected with 3-BP largely unformulated. This really not a great idea. 3-BP can decompose into HBr (hydrobromic acid is a strong acid). Patients have noted how painful these acids can be for veins. Formulating the treatment properly would avoid these problems. Unfortunately, clinical research on these lines does not appear to have to been conducted. 

It is also important not to become entirely focused on 3-BP. We have finally seen substantial confirmations of the metabolic approach emerging from Turkey's Chemothermia clinic. They have many of the well known metabolic treatments (their website has also mentioned that they have used 3-BP in the past (perhaps presently as well)). Their patient series with lung cancer using metabolics was highly impressive 40+ month survival in advanced patients (vs. historical controls of roughly 8 months).

There are so many metabolic treatments that we have encountered over the years; it is surprising how many have demonstrated efficacy. We have been interested in 3-BP for so many years (it clearly has some limitations in that it should be administered under reasonable medical supervision), though when the dog dewormer (Fenbendazole) hit the headlines there was a near global buying panic. Without the need for IV dosing, a medical prescription, or concern for TLS, FB had considerable advantages.  

Awareness has been growing about metabolic cancer treatment and as treatments move to the clinic we could finally see a well researched product that can consistently help patients.

 

       


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NA
 NA
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Finally, soon (in a few days) we will launch the supplement company and I will have time again to allocate to our nice discussions here and address new treatment options. So I am happy to see you back J, and hope to see you more often again as it is always a pleasure 😉

Kind regards,
Daniel

That's fantastic news, D! 


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Jcancom
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manuone, exactly!

Imagine being able to rotate out of a cancer treatment after only one day and then on to another. Or even better, have a subclinical dosing to establish that response will occur even before a treatment dose.

Clinical trials today do not even pick up on this important aspect of being able to quickly establish treatment efficacy. They could say, well 3-BP did not work for that patient. Yet, that is not necessarily the primary consideration. It is important that minimal time was wasted in establishing that it was not effective. Other cancer treatments can take months or even years to reach such a conclusion. Think about all those patients who often are non-responders in those trials. All that time on the trial has been at the cost of not trying other potential therapies. Metabolics have a near unbeatable advantage over all of these other treatments.  


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Daniel
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@johan

Thank you Johan. Btw, I was speaking on the phone during the past days with https://www.cancertreatmentsresearch.com/community/profile/adifer/ who is dealing with a brain-stem glioma of his child. It seems that they had some good response with PhenylButyrate (large reduction on two dimensions but a little longer in high and that brings some difficult complications that hopefully they will solve - adi will post here an update asap).

Kind regards,
Daniel


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Jcancom
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D, I think we did totally miss this article. It is a very good one. It shows how important it is to do one's homework. There are hundreds and hundreds of articles on 3-BP, one really does need to go through them all carefully. This was exactly what I had been thinking for a long time on the compass: how can we show with imaging that rapid responses occur with 3-BP. The patient reports clearly suggested that this was happening, though showing imaging with a rapid reduction in FDG uptake makes it all too dramatically clear.  

D, what might be of dramatic benefit in humans would be intratumoral (e.g. skin cancers). The Toronto clinic was using 3-BP with intra-tumoral application. It must have been highly effective because there are already highly effective intra-tumoral cancer therapies. An FDG PET for such a tumor might show very profound anti-cancer effects quite rapidly.

Yes, this is great news about the supplement company. I realize that it is important for you to establish a financially sustainable base for doing what you love. Thank you for your kind words. I am glad to be back with my friends on forum, might not be 100%, but it's nice to be back and nice to know that I have been missed. I appreciate all the well wishes from my friends.

The compass forum has been closed, so the forum will now be my home base for posting. 

 

 


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NA
 NA
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Posted by: @daniel

@johan

Thank you Johan. Btw, I was speaking on the phone during the past days with https://www.cancertreatmentsresearch.com/community/profile/adifer/ who is dealing with a brain-stem glioma of his child. It seems that they had some good response with PhenylButyrate (large reduction on two dimensions but a little longer in high and that brings some difficult complications that hopefully they will solve - adi will post here an update asap).

Kind regards,
Daniel

That's the best news!! ? 


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Daniel
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@johan Yes, Johan, its nice to hear about the effectiveness of PhenylButyrate but let-s hope and pray they solve the complications related to the progression on the other axis. Kind regards, Daniel


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Daniel
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Posted by: @jcancom

D, I think we did totally miss this article. It is a very good one. It shows how important it is to do one's homework. There are hundreds and hundreds of articles on 3-BP, one really does need to go through them all carefully. This was exactly what I had been thinking for a long time on the compass: how can we show with imaging that rapid responses occur with 3-BP. The patient reports clearly suggested that this was happening, though showing imaging with a rapid reduction in FDG uptake makes it all too dramatically clear.  

D, what might be of dramatic benefit in humans would be intratumoral (e.g. skin cancers). The Toronto clinic was using 3-BP with intra-tumoral application. It must have been highly effective because there are already highly effective intra-tumoral cancer therapies. An FDG PET for such a tumor might show very profound anti-cancer effects quite rapidly.

Yes, this is great news about the supplement company. I realize that it is important for you to establish a financially sustainable base for doing what you love. Thank you for your kind words. I am glad to be back with my friends on forum, might not be 100%, but it's nice to be back and nice to know that I have been missed. I appreciate all the well wishes from my friends.

The compass forum has been closed, so the forum will now be my home base for posting. 

 

 

Thanks J. Indeed, financial sustainability is very important if we want to move projects such as 3BP from dreaming to reality. Trust me, with the supplement company, we will be the first forum group who will get to the point of having the capability to move projects such as 3BP to clinical space. I work hard for that and promises that will happen, and it will only take a few years to get there.

The compass admins were anyway behaving strangely. I tried to answer some people and they would not publish my post. I tried to send private msg, but I was not allowed. I am not sure what made them changed - it was so good some years ago.

 

 

 


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Posted by: @daniel

@johan Yes, Johan, its nice to hear about the effectiveness of PhenylButyrate but let-s hope and pray they solve the complications related to the progression on the other axis. Kind regards, Daniel

I'm praying they will, considering how unresponsive DIPG is to standard treatment this gives hope.  


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NA
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Posted by: @johan
Posted by: @daniel

@johan Yes, Johan, its nice to hear about the effectiveness of PhenylButyrate but let-s hope and pray they solve the complications related to the progression on the other axis. Kind regards, Daniel

I'm praying they will, considering how unresponsive DIPG is to standard treatment this gives hope.  

This is an interesting study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5670105/

 "As only non-molecularly charged, lipophilic, and relatively small sized drugs are likely to passively diffuse through the BBB, out of 51 drugs modeled, only 8 (15%)—carmustine, lomustine, erlotinib, vismodegib, lenalomide, thalidomide, vorinostat, and mebendazole—are theoretically qualified for systemic administration in DIPG. " 

I read about a patient responding (+ 1 year) to radiation coupled with Vorinostat. Interestingly Vorinostat is an HDACi, as is PB.

I'm thinking metronomic chemotherapy could be an option to explore(considering the above).

Panobinostat: https://pubmed.ncbi.nlm.nih.gov/28234741/

Extreme dose rate proton therapy:
https://www.thebraintumourcharity.org/brain-tumour-diagnosis-treatment/adult-brain-tumour-research/extreme-dose-rate-proton-therapy/

On a mission to beat childhood brain tumours:
https://www.thebraintumourcharity.org/brain-tumour-diagnosis-treatment/child-brain-tumour-research/finding-new-treatments-for-aggressive-childhood-brain-tumours/

https://www.researchgate.net/publication/287252184_Curcumin_for_the_Treatment_of_Glioblastoma
https://pubmed.ncbi.nlm.nih.gov/27543754/

 

 


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Daniel
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@johan Thank you Johan! I will add here @adifer so he will be notified too.

Kind regards,
Daniel


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NA
 NA
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Posted by: @daniel

@johan Thank you Johan! I will add here @adifer so he will be notified too.

Kind regards,
Daniel

Combined Therapy of AXL and HDAC Inhibition Reverses Mesenchymal Transition in Diffuse Intrinsic Pontine Glioma by Selleckchem | Jun 11 2020:

https://www.selleckchem.com/blog/Combined-Therapy-of-AXL-and-HDAC-Inhibition-Reverses-Mesenchymal-Transition-in-Diffuse-Intrinsic-Pontine-Glioma.html

 

Identification of new therapeutic targets and natural compounds against diffuse intrinsic pontine glioma (DIPG). Apr 22, 2020:

https://www.physiciansweekly.com/identification-of-new-therapeutic-targets-and-natural-compounds-against-diffuse-intrinsic-pontine-glioma-dipg/

 


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Jcancom
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D, this is very good news about your intentions for the supplement company. There are so many formulations that could enhance treatment efficacy. If we could develop the skill set necessary, then there might be a great deal of potential to help patients. Having a good understanding of what was within the rules would be important: Where is the line between a supplement and a treatment?

Yes, the compass had become more frustrating through time. They were taking days to approve my posts and they also blocked my personal messages. Nevertheless they were one of the only online forums that allowed honest discussion about 3-BP. Virtually every single other forum did not want to be associated with it. 


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Daniel
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@jcancom Hi J, just for clarity: the supplement company will donate 50% of its profits to selected projects such as 3BP without expecting anything in return, other than the benefits for cancer patients.

The line between supplement and treatment is very well defined by regulations. Supplements can not be claimed as treating any disease. And that is good because there are so many out there desperate to make money. One such supplement manufacturer (I am not going to give names here) I see selling even Fenbendazole as a supplement when that is a drug for animals. Crazy.


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Jcancom
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D, this is great! This is exactly what we need! We need money to do interesting research (as you mentioned). Perhaps we could even find benefactors who could help us out. Oftentimes money becomes more of a distraction than a help; People then focus on the money and not on trying to achieve their goal. However, when you have thought about something carefully for a long time, then you can start to see ways that money could be productively spent.

With some "soft" money that could be directed in exploratory research we could investigate some interesting questions. Consider for example, the FDG PET scan idea for 3-BP. These scans are not that overly expensive. Possibly ~US $1,500. I have seen prices for FDG PET much lower in some developing nations ~ $300. A before (3-BP) and after (3-BP) scan done 2 days apart could show the extreme potential of 3-BP. It has been endlessly frustrating over all of these years not having a strong rebuttal to those who claim that 3-BP is ineffective. The argument could be stopped immediately if we could pull out some PET scans. We could even load the dice in our favor by simply using a pre-treatment dose and checked for response in biomarkers (of course, in this instance we would be transparent about our selection methods). Finally getting this important information out to patients would be a valuable public service. With a bit of extra money that we could access, we could help patients in this way.


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NA
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Posted by: @johan

DIPG tumors are sensitive to cholesterol interference

Posted by: @daniel

@johan Thank you Johan! I will add here @adifer so he will be notified too.

Kind regards,
Daniel

Combined Therapy of AXL and HDAC Inhibition Reverses Mesenchymal Transition in Diffuse Intrinsic Pontine Glioma by Selleckchem | Jun 11 2020:

https://www.selleckchem.com/blog/Combined-Therapy-of-AXL-and-HDAC-Inhibition-Reverses-Mesenchymal-Transition-in-Diffuse-Intrinsic-Pontine-Glioma.html

 

Identification of new therapeutic targets and natural compounds against diffuse intrinsic pontine glioma (DIPG). Apr 22, 2020:

https://www.physiciansweekly.com/identification-of-new-therapeutic-targets-and-natural-compounds-against-diffuse-intrinsic-pontine-glioma-dipg/

 

 

- Fluoxetine as an antidepressant medicine improves the effects of ionizing radiation for the treatment
of glioma (May 2020):

https://www.researchgate.net/publication/341366519_Fluoxetine_as_an_antidepressant_medicine_improves_the_effects_of_ionizing_radiation_for_the_treatment_of_glioma

- Dual Inhibition of PI3K/AKT and MEK/ERK Pathways Induces Synergistic Antitumor
Effects in Diffuse Intrinsic Pontine Glioma Cells:
"concomitant HDAC and proteasome inhibition appears to be a promising therapeutic strategy
that targets metabolic vulnerabilities in DIPG."

https://www.sciencedirect.com/science/article/pii/S1936523316301383

- Promising drug combination against lethal childhood brain cancers(panobinostat and marizomib):

https://www.nih.gov/news-events/news-releases/scientists-find-promising-drug-combination-against-lethal-childhood-brain-cancers

 

 


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Daniel
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@jcancom Hey J. I am very happy you understand the relevance of the supplement company in generating the support required to do so much more for cancer patients. I just posted the announcement on the start up of the company https://www.cancertreatmentsresearch.com/our-mcs-formulas-food-supplement-company-is-up-and-running/


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Jcancom
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D, this is great! Cancer is the great chameleon, so we need to be adaptive as well. At a certain point the returns from yet more science begins to diminish and other points of view (political, social empowerment etc.) need to be brought online. It is quite positive that you are pursuing this new venture.

Are you considering formulations of your products? For example, liposomal (etc.) honokiol (etc.)? Supplement companies do seem to offer such formulations e.g. liposomal vitamin C, though I am not entirely sure where the line might be drawn between supplement and drug with such formulations. For example, would nano-methylglyoxal (MG is a naturally occurring chemical, nano for chitosan formulation) be considered to be a supplement?

Best Wishes on your new enterprise, J


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Daniel
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@jcancom Hi J,

Thanks a lot! Totally agree. At some point we need to do more. Very good examples are metronomic 2DG or 3BP or Salinomycin. I had enough of repeating the story of these. It's clear: the science is there, the lab results are there, the clinical results are there. We need to move on. I mean we, the society. Otherwise I better stop with all this and go to a normal life, normal job, nice holidays, weekends with BBQ, evenings at the TV. Yes, I dream back to all these, but I think we have a responsibility and this is why I chose to spend my days and nights working on oncology. I think we are not far from getting to breakthroughs. There are many good people in this world. But we need to unite our efforts and move from all possible directions to make a change. Coronavirus- times demonstrated that the world can move in a coherent manner against a diseases. Let's do that against cancer too!

Kind regards,
Daniel


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