Bozzi, Fabio published the artcileMIF/CD74 axis is a target for novel therapies in colon carcinomatosis, HPLC of Formula: 41270-96-6, the publication is Journal of Experimental & Clinical Cancer Research (2017), 16/1-16/15, database is CAplus and MEDLINE.
Background: Strategies aimed at obtaining a complete cytoredn. are needed to improve long-term survival for patients with colorectal cancer peritoneal carcinomatosis (CRC-pc). Methods: We established organoid models from peritoneal metastases of two naïve CRC patients. A standard paraffin inclusion was conducted to compare their 3D structure and immunohistochem. profile with that of the corresponding surgical samples. RNA expression levels of the CRC stem cell marker LGR5 was measured by in situ hybridization. The secretome of organoids was profiled by mass spectrometry. Energy homeostasis of organoids was interfered with 4-IPP and metformin. Biochem. and metabolic changes after drug treatments were investigated by western blot and mass spectrometry. Mitochondria impairment was evaluated by electron microscopy and mitotraker staining. Results: The two organoids recapitulated their corresponding clin. samples in terms of 3D structure and immmunoistochem. profile and were pos. for the cancer stem cells marker LGR5. Proteomic analyses of organoids highlighted their strong dependence on energy producing pathways, which suggest that their targeting could be an effective therapeutic approach. To test this hypothesis, we treated organoids with two drugs that target metabolism acting on AMP-activated protein kinase (AMPK), the main regulator of cellular energy homeostasis, which may act as metabolic tumor suppressor in CRC. Organoids were treated with 4-IPP, an inhibitor of MIF/CD74 signalling axis which activates AMPK function, or metformin that inhibits mitochondrial respiratory chain complex I. As a new finding we observed that treatment with 4-IPP downregulated AMPK signalling activity, reduced AKT phosphorylation and activated a JNK-mediated stress-signalling response, thus generating mitochondrial impairment and cell death. Metformin treatment enhanced AMPK activation, decreasing the activity of the anabolic factors ribosomal protein S6 and p4EBP-1 and inducing mitochondrial depolarization. Conclusions: We provide evidence that the modulation of AMPK activity may be a strategy for targeting metabolism of CRC-pc organoids.
Journal of Experimental & Clinical Cancer Research published new progress about 41270-96-6. 41270-96-6 belongs to iodides-buliding-blocks, auxiliary class Pyrimidine,Iodide,Benzene,Immunology/Inflammation,MIF, name is 4-Iodo-6-phenylpyrimidine, and the molecular formula is C10H7IN2, HPLC of Formula: 41270-96-6.
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https://en.wikipedia.org/wiki/Iodide,
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