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Role of glutamine and its metabolite ammonia in crosstalk of cancer-associated fibroblasts and cancer cells


johan
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"Cancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, play an indispensable role in cancer initiation, progression, metastasis, and metabolism. The limitations of traditional treatments can be partly attributed to the lack of understanding of the role of the tumor stroma. For this reason, CAF targeting is gradually gaining attention, and many studies are trying to overcome the limitations of tumor treatment with CAF as a breakthrough. Glutamine (GLN) has been called a “nitrogen reservoir” for cancer cells because of its role in supporting anabolic processes such as fuel proliferation and nucleotide synthesis, but ammonia is a byproduct of the metabolism of GLN and other nitrogenous compounds. Moreover, in some studies, GLN has been reported as a fundamental nitrogen source that can support tumor biomass. In this review, we discuss the latest findings on the role of GLN and ammonia in the crosstalk between CAFs and cancer cells as well as the potential therapeutic implications of nitrogen metabolism."

https://cancerci.biomedcentral.com/articles/10.1186/s12935-021-02121-5


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Daniel
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Thanks @j 

Fibroblast are a very important subject in oncology. They are those that fuel cancer growth even when there are no more blood vessels at the tumor. This is an important resistance mechanism to angiogenesis inhibitors. They are those rescuing tumors when tumors are suddenly damaged. They can help tumor grow faster than before the damage (induced via e.g. radiation).

Fibroblast function relies on fermentation. This one other reason why glycolisis inhibitors are so helpful.

The last case presented in this article https://www.cancertreatmentsresearch.com/10-cases-of-complete-remission-from-stage-4-cancers-after-using-supplements-or-repurposed-drugs/ demonstrated the power of effective fibroblast inhibition.

Kind regards,

Daniel

 

 


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johan
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@daniel 

yes such a great example, you see these advanced cancers receding within a matter of days given the right treatment, it shows what can be achieved even in those latest stages of cancer


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johan
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johan
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Posted by: @daniel

This one other reason why glycolisis inhibitors are so helpful.

 

I was thinking of the following strategy:

Butyrate (preferentially induces apoptosis in glycolytic cells) followed by Citric acid (Glycolysis inhibitor).


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Daniel
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@j Thank you for sharing the thought. Both are indeed outstanding supplements.

Kind regards,
Daniel


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johan
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Posted by: @daniel

@j Thank you for sharing the thought. Both are indeed outstanding supplements.

Kind regards,
Daniel

Indeed. The results Dr. Alberto Halabe achieved with only citric acid: http://www.journalijar.com/uploads/118_IJAR-17108.pdf

My theory is that citric acid treatment might be even more effective if the patient is treated first with supplements to increase butyrate, such as Tributyrin. And I'd add phenyl-butyrate.

A low-carb, high-fat (or high-protein) diet can lower butyrate production, a high fiber diet would be a better option during such treatment (and probably after treatment as well). 


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