Minerval!!! Targeti...
 

Minerval!!! Targeting the Cancer's Lipid Membrane!  

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Jcancom
(@jcancom)
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25/01/2019 6:39 pm  

Minerval!

This is the first in a new line of cancer treatment targeting the abnormal lipids found in cancer. It might be related to the findings from the Brazilian bee research. A recently completed clinical trial used very large doses that apparently were non-toxic. This looks to be close to a natural product, so sourcing it should not be overly difficult.  

http://www.bioscirep.org/content/39/1/BSR20181661.full-text.pdf

http://www.lipopharma.com/index.php/en/


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Daniel
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25/01/2019 7:59 pm  

Very intresting J. Do you know where you can get Minerval (2-Hydroxyoleic acid) in high quantities?

Here are some nice slides on the same  https://www.medicamentos-innovadores.org/sites/default/files/medinnovadores/Español/Eventos/2011/13_04_2011_FarmaBiotech_Onco/present_lipopharma_pharmaind_minerval_abr11.pdf

It seems that it is most relevant to brain cancer. Should I move this topic you started to the brain c section?


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Jcancom
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25/01/2019 9:11 pm  

D is quite remarkable! They dosed up to 16g in a clinical trial and then decided on a tolerated dose of 12 grams! The article below suggests that adding in glycolysis inhibitors such as 2-DG etc. might combine well. Research also talks of how biomarkers might help in selecting responders.

http://www.bioscirep.org/content/39/1/BSR20181661.full-text.pdf

I can see what you mean about the supply issue. The chemical houses have it ... at an extraordinarily high price. Oleic acid can be bought online by the gallon, yet add in another double bonded oxygen and the price increases dramatically.

If you like you could move this to the Brain Cancer Section, though it might have wider applicability. They might want to start with brain cancer as an orphan indication.

Best Wishes, Jcancom 


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Daniel
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25/01/2019 9:45 pm  

J, I sent the info to Manuel - the company is Spanish and as they speak the same language, the co may decide to help them on compassionate basis with the product. Kind regards, Daniel


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Jcancom
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25/01/2019 9:58 pm  

Great Thinking D! I though that might be a good work around.


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Jcancom
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25/01/2019 10:01 pm  

It is frustrating, though how all you need to do is add a hydroxyl right by the COOH and you could convert oleic acid to 2-hydroxyoleic acid. Unfortunately, it isn't that easy.


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Jcancom
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28/01/2019 6:47 pm  

D, 2-hydroxyoleic acid has potential, especially due to its super low toxicity. Attacking the unique chemistry of the cancer cell membrane opens up an entirely new frontier of opportunity in cancer medicine.

Page 10 of the patent describes the synthesis

https://patents.google.com/patent/US20140288176A1/en?oq=US+2014%2f028817.6+A1

 


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Almo
 Almo
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03/10/2019 2:23 pm  

Has anyone use this agoainst glioblastoma?results?


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Daniel
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03/10/2019 5:48 pm  

@almo

Hi Almo, I think Manuel used this product but if I remember correctly there was not much benefit from it. Please check with Manuel.

Kind regards,
Daniel


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Jcancom
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04/10/2019 5:41 am  

D, this is so great! There is so much energy on this forum as others find useful ideas and look into them. This is what you always intended: create a clearinghouse of ideas that could help narrow things down for people. Seeing all the new people who see the value here is very rewarding. Now that you have a summary page the info here could be of even greater benefit. Perhaps having another webpage devoted to the distillation of our knowledge would be even better. There can be so much commentary on this forum that it might stand in the way to treatment for some patients. A page with only the facts might be of help to them.

Great Job D! Best Wishes, J

 


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Almo
 Almo
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04/10/2019 8:51 am  

@daniel thank you! I will try contact @manuone

 


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Daniel
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04/10/2019 4:04 pm  

@jcancom

Hi J, Thnak you! Step by step we will do a lot. And I think at some point we can even pay for some things to be done so that we can advance even faster. That is my dream with the supplement company that I will start in a few months (profit of which 50% will go to research, etc.). Imagine there will be one day when we can support financially research groups to advance fast the valuable findings. I am sure that day will come. Kind regards, Daniel


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johan
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04/10/2019 4:15 pm  

@daniel

sounds absolutely fabulous Daniel!


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Jcancom
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05/10/2019 5:22 pm  

D, did you see this one? Glycogen! Amazing yet another metabolic target. Perhaps this explains how cancer can withstand merely glucose restriction. Also pressing glycogen could offer yet another lever. It continues to surprise me how interlocked cancer truly is to metabolism, but it essentially has to be doesn't it? Cancer simply is so interwoven with metabolic dysfunction. From this vantage, point one would suspect almost anything along these metabolic pathways will be distorted. 

https://www.sciencedaily.com/releases/2019/10/191004132341.htm

Hmm, you know D, this might be another great request that I could make of you; a figure of the full metabolic circuit diagram. wiki linked to an online resource that showed it in full detail. This shows the central mechanisms open for cancer to exploit.   

This one is actually a condensed version.  

 

 


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Jcancom
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05/10/2019 5:28 pm  

Whoa! Very cool! I did not know that you could even do that. The image just pasted into the above post. johan's avatar is very cool, yet my post above might be viewed by the forum as even a notch above.

Add "https:" in front of the text below to form the url for the jpg image. When I paste the full url the forum software automatically posts the image itself which I do not want. By navigating to the url you can magnify the image, though this is not possible with my post above. 

//upload.wikimedia.org/wikipedia/commons/a/a8/Human_Metabolism_-_Pathways.jpg


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Jcancom
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05/10/2019 5:49 pm  

This is the one that I was actually thinking about. This is the entire metabolic map of humans.

http://biochemical-pathways.com/#/map/1

 

The one below is from wiki and is more abbreviated; actually it is much easier to see and understand what is going on.   https://en.wikipedia.org/wiki/Metabolic_pathway

(for some reason the labels did not paste in with the figure)

Metro-style map of major metabolic pathways


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Jcancom
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05/10/2019 6:05 pm  

This is beta oxidation. One thing that has been in the recesses of mind for a while is: why not overload the cell with NADH with beta oxidation? The idea here would be increase NADH and then turn off OXPHOS subunit 1 that processes it with perhaps Methylglyoxal. Why would you want to do this, as you would also be making a lot of ATP with the acetyl--COA (10 per cycle)? Well, for one you would have rerouted the glycolysis pathway, perhaps this would mean less lactate export. Also the NADH to NAD+ ratio would change; this ratio has substantial relevance for how the cell controls internal processes. This might be one to investigate further.   

Cn-acyl-CoA + FAD + NAD+
+ H
2
O
+ CoA → Cn-2-acyl-CoA + FADH
2
+ NADH + H+
+ acetyl-CoA


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johan
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05/10/2019 6:14 pm  

lol, definitely a notch or two above my avatar, J.!

It's funny you posted this picture of the metabolic pathways today b/c just yesterday I was thinking of buying one of those metabolic pathway posters to hang in my office.

 


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Jcancom
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05/10/2019 6:37 pm  

johan, I would say go for it. Of course, it is always easier to spend other people's money. Yet, these metabolic pathways really are what we have spent the last many years discussing endlessly. When you have the metabolic pathway map you have a bird's eye view of what is actually happening and a much better sense of how the overall network functions and how it interacts.

The great thing with this map is that this is all there is, there is no logic that is somehow external to it. Cancer is essentially imprisoned in this logic which is an extraordinary limitation. If you were able to shut-down all the pathways of energy selectively for cancer, that would be it. There would then be no hidden trick that it could use. There are actually fewer pathways on the figure than one might have suspected (especially the "subway" map on wiki that I posted above, the Roche one is quite intense. It is likely true that it would be naive to think that there is a simple single "answer" that one could derive from these figures, yet being able to jolt cancer with e.g., the idea of going through beta-oxidation and then shutting off OXPHOS and overloading the cell with NADH, or depleting glycogen and then returning with a glucose reduction strategy could be the next generation of ideas that some on the forum might be able to apply to exploit another dimension of cancer weakness.  

A 15 minute daily mediation on such a map would certainly increase your state of cancer consciousness. I am sure such deliberations would be much more instructive than a calm blue ocean etc..


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Shanti
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05/10/2019 7:05 pm  

This is the one I use, the same as what Jcancom linked to: http://biochemical-pathways.com/#/map/1.

You can actually download the poster for printing here: https://www.roche.com/sustainability/philanthropy/science_education/pathways/pathways-ordering.htm I printed it out on 8x11 paper and taped them together with 4 inch wide packing tape so it is like they are laminated.  Then you can draw on it with dry-erase markers.  Such a nerd, I know, lol. 


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Jcancom
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05/10/2019 7:13 pm  

Shanti, that is very impressive! The Roche figure is almost too much information. However, the way I see it is usually best to let yourself be exposed to the full intensity of a challenge and then let yourself grow into the challenge. At first it seems completely overwhelming, however, after a while it is no big deal. The problem that many people seem to make is that they never allow themselves to go omniscient so they are perpetually stuck with an impoverished vocabulary, point of view etc. Nonetheless, also having the "subway" map can give you reference point as the Roche can be difficult to navigate around. 


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Manuone
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05/10/2019 7:20 pm  

Hi guys! I am alive and healthy! haha
For four days I have not had any side effects! Next week my mother will start but practically in monotherapy without adding drugs at the moment.
This is the plan:
- First week: "new molecule"
- Second week: "new molecule" + the usual cocktail
- Third week: ¨new molecule x2 "+ the usual cocktail
I have not found interactions with other drugs and having no answers I clearly choose to risk.
It is true that mitochondrial toxic accumulation should be taken into account. It is possible that in vivo this toxicity does not occur but if there is in vitro evidence of mitophagy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880956/

kind regards


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Shanti
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05/10/2019 7:21 pm  

@jcancom

Yes, it really is too much, especially because the printable chart from Roche has higher plants and bacteria pathways on it too!  Although there is a certain beauty about it all together on one chart, I am thinking of getting a simpler one though, for practicality.  Meanwhile, I am going to work on going omniscient ❤️ .


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Shanti
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05/10/2019 7:33 pm  

@manuone

Hi Manuone, It is really great to hear from you, alive and well, and even without side effects. Glad to see you posting.

-Shanti


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johan
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05/10/2019 8:42 pm  

@manuone

well done and good luck next week with the new addition to your mother's treatment plan. I'm sure it'll work out great!


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Jcancom
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05/10/2019 8:57 pm  

Manuone, I have been so worried! Thank you for posting! While some of the other posters have shown their emotional power more openly (notably erg), even those of a more reserved inclination have emotional stirrings as well.It clearly demonstrates your integrity that you chose the "doctor's commitment" of taking the medicine that you would prescribe and treat with.

You are perhaps one of the only humans to have ever tried this molecule, so it truly is about breaking new ground. I am glad that you are thinking of this in terms of first monotherapy, I understand that the sort of endless caution that is shown in clinical trials is not available to you, though considering the power of this treatment it seems wise to take heed. You need some sense of the response and effects of this, which dose escalation can effectively provide. Adding in anti-glycolytics such as 2-DG as suggested in the patent could also amplify effectiveness. Perhaps it would be good to go back to the patent and figure out what molarity would be applicable in vivo in humans. At certain combo doses there was especially effective synergistic power. 


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johan
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06/10/2019 1:39 am  

there´s also synergy with that other lignan, Manuel.

 


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Jcancom
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06/10/2019 2:39 am  

Wow, good one johan! The article below used from best that I can tell ~ 1mg/kg (Second paragraph of Discussion). They did reference 20x higher though I do not know if they actually included those results; they did mention that there were no side effects even at this dose. Your figure shows 20 mg/kg! Very large effect. State your sources! I am not sure where your figure is sourced from.

https://www.sciencedirect.com/science/article/pii/S2589004218300452


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Jcancom
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06/10/2019 3:07 am  

johan, man, there are 187 TMZ HNK articles that is too many to go through. Help us out which one?

Found it! This is just scary. We could be looking at massive massive levels of effectiveness. I did not realize it but your figure was only talking about neat Honokiol.  Did your figure even include the TMZ in the combo? Strange part is that I remember a video where they noted that TMZ in GBM might not actually have no effect that it might relate more to a ketogenic effect.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045382/

This could become a pile-on. Once we have a nice strong lever to work within the new addition then we could find these synergistic add-ons that greatly add power. Nice one johan!


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johan
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06/10/2019 5:37 am  

Thanks, J.! TMZ continues to be the standard treatment for GBM, it amazes me.


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