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We're Not "DON" Yet: Optimal Dosing and Prodrug Delivery of 6-Diazo-5-oxo-L-norleucine ... - 0 views

www.ncbi.nlm.nih.gov/...PMC6130910 glutamine DON dosing cancer
shared by Nathan Goodyear on 17 Mar 24 - No Cached
  • Glutamine is the most abundant amino acid in blood
  • Rapidly proliferating healthy cells (GI epithelium, lymphocytes) or cells under physiologic stress have increased demand for glutamine
  • Glutamine is transported into cells by one of multiple amino acid transporters (e.g. ASCT2, BOAT2), several of which are thought to be upregulated in cancer cells
  • ...10 more annotations...
  • it is hydrolyzed to glutamate and ammonia by glutaminase (‘glutaminolysis’)
  • Glutamate, produced from glutamine by glutaminase and glutamine amidotransferase activities, may be further metabolized to alpha ketoglutarate and provide a carbon skeleton source for the mitochondrial tricarboxylic acid cycle (TCA cycle)
  • Glutamine-derived glutamate is also involved in the synthesis of the reducing equivalent glutathione, vital to maintaining cellular redox status
  • Many tumors become largely dependent on glutamine to provide carbon and nitrogen building blocks needed for proliferation
  • In cancer model systems, Eagle and colleagues first demonstrated tumor cells in culture require supplementation with exogenous glutamine for efficient proliferation
  • It was subsequently shown that when deprived of glutamine tumor cells undergo apoptosis
  • The most well-characterized oncogene to regulate glutamine metabolism is MYC (9), which enhances glutaminase expression, upregulates glutamine transporters, and enhances glutamine utilization in energy production and biosynthesis
  • Other pro-tumorigenic regulators such as KRAS and mTOR, as well as tumor suppressors (p53, VHL) have also been associated with alterations in glutamine metabolism
  • Tumor cells are highly adaptable and alter nutrient uptake and metabolic networks to resist single agent glutaminase inhibition
  • cells in the microenvironment of several tumor types upregulate glutamine production, thereby enabling tumor cells to escape glutaminase inhibition
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Press-pulse: a novel therapeutic strategy for the metabolic management of cancer - PMC - 0 views

www.ncbi.nlm.nih.gov/...PMC5324220 metabolic disease Press-pulse cancer Thomas seyfried metabolic reprogramming
shared by Nathan Goodyear on 18 Mar 24 - No Cached
  • Nathan Goodyear on 18 Mar 24
     
    Bench to clinical application
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The impact of the microbiome in cancer: Targeting metabolism of cancer cells and host -... - 0 views

www.ncbi.nlm.nih.gov/...PMC9708872 tumor microbiome cancer gut microbiome TME metabolism
shared by Nathan Goodyear on 20 Mar 24 - No Cached
  • Nathan Goodyear on 20 Mar 24
     
    Studies have found that high-salt diet can enhance the function of natural killer (NK) cells by enriching the abundance of Bifidobacterium, thus inhibiting tumor growth (63). High dietary fiber can enrich A. muciniphila, activate innate immunity, reshape the tumor microenvironment, and exert the function of inhibiting tumor (64). Notably, Wargo et al. have confirmed that high-dietary fiber diet can enhance anti-tumor immunity and increase the infiltration of tumor-killing T cells, while commercial probiotics treatment alone does not enhance the efficacy of immunotherapy. This study suggests that probiotics intervention is strain-specific and should be put in a specific dietary environment to make sense, to some extent (65).
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Vitamin C and Doxycycline: A synthetic lethal combination therapy targeting metabolic f... - 0 views

www.oncotarget.com/...text vitamin C doxycycline CSC cancer stem cells
shared by Nathan Goodyear on 27 Mar 24 - No Cached
  • Nathan Goodyear on 27 Mar 24
     
    vitamin C + doxy inhibits CSC
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