The function of metformin in colorectal cancer (CRC) patients with diabetes mellitus (DM) remains a controversial topic because studies are increasingly focusing on epidemiologic features. We examined Notch1/Hes1 signaling in CRC with DM (DM-CRC) and investigated alterations in signaling caused by metformin treatment. For this purpose, information on pathological characteristics was collected from each patient. The proliferation of epithelium labeled with proliferating cell nuclear antigen and the differentiation of goblet cells were investigated using immunohistochemistry and periodic acid-Schiff staining, respectively. The factors involved in Notch1/Hes1 signaling were detected using qRT-PCR and western blot. In our study, we found that lymphatic metastasis, pTNM staging, and the carcinoembryonic antigen level were significantly different between groups. The depth of crypts and the rate of proliferating cell nuclear antigen-positive cells were distinctly higher in DM-CRC and patients who were managed with insulin. Moreover, the goblet cell differentiation rate was decreased in DM-CRC. The expression of Dll1, Notch1, Math1, and RBP-Jκ was increased in DM-CRC, whereas the expression of Dll4 and Hes1 was decreased in this group in normal tissue. In CRC tissue, the expression of Dll1 and Notch1 was clearly higher than that in DM-CRC. Furthermore, the trend in these changes was aggravated with insulin management and alleviated with metformin treatment. In conclusion, the abnormal cell proliferation and differentiation observed in DM-CRC are correlated with overactivated Notch1/Hes1 signaling, which is potentially relieved by metformin treatment.
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Publication date: Available online 18 January 2017 Source: Free Radical Biology and Medicine Author(s): Jayne Louise Wilson, Frédéric Boui...
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Publication date: March 2017 Source: Free Radical Biology and Medicine, Volume 104 from #AlexandrosSfakianakis via Alexandros G.Sfak...
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Publication date: July 2017 Source: European Journal of Cancer, Volume 79 Author(s): Simon Pernot, Cecile Badoual, Magali Terme, Florence...
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Introduction. The incompleteness of medical records is a significant problem that affects the quality of health care services in many hospit...
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Abstract Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenetic disorder that is caused by mutations in the genes PK...
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Inflammation is an important component of diabetic retinal damage. We previously reported that a novel β-adrenergic receptor agonist, Compou...
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An ambitious plan to save a melting glacier in the Swiss Alps with showers of artificial snow will be tested this summer from #AlexandrosS...
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by Yiquan Wu, Adrian Prager, Simone Boos, Moritz Resch, Ilija Brizic, Michael Mach, Sabrina Wildner, Laura Scrivano, Barbara Adler Herpesv...
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Abstract The aims of this study were to (1) determine if older people at their fast walking speed (FWS) are able to reach the speed require...
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