Celyad Oncology SA, announced that the Company has entered into a clinical trial collaboration with MSD, a tradename of Merck & Co., Inc., through a subsidiary. Celyad Oncology will conduct the Phase Ib KEYNOTE-B79 clinical trial, which will evaluate Celyad Oncology’s investigational non-gene edited allogeneic CAR T candidate, CYAD-101, following FOLFIRI preconditioning chemotherapy, with MSD’s anti-PD-1 therapy, KEYTRUDA® in refractory metastatic colorectal cancer patients with microsatellite stable/ mismatch-repair proficient disease.
Recent studies investigating the role of MHC class II+ exosomes released by Intestinal epithelial cells report conflicting findings of either immune enhancing or immunosuppressive activities. In addition to modulating inflammatory responses, recent findings suggest that MHC class II expression by intestinal stem cells may elicit crosstalk that promotes epithelial renewal.
Morphic Therapeutic announced that the first healthy volunteers have received MORF-057 in a Phase I clinical trial designed to evaluate MORF-057’s safety and pharmacokinetic profile in addition to predictive pharmacodynamic signals. MORF-057 is in clinical development as an oral small molecule inhibitor of the α4β7 integrin for the treatment of inflammatory bowel disease with an initial focus on ulcerative colitis.
Researchers showed that Rab13 regulated the secretion of small extracellular vesicles (sEVs) corresponding to both traditional exosomes and a novel subset of vesicles containing both β1-integrin and Rab13. They found that exposure of recipient cells to sEVs from KRAS mutant donor cells increased proliferation and tumorigenesis and that knockdown of Rab13 blocked these effects. Thus, Rab13 serves as both a cargo protein and as a regulator of sEV secretion.
Investigators evaluated aspirin-mediated effects on phenotype and stem cell markers in intestinal organoids derived from mouse and human familial adenomatous polyposis patients. colorectal cancer cell lines were used to study effects on motility, invasion, Wnt signalling and epithelial-mesenchymal transition.
[Cellular and Molecular Gastroenterology and Hepatology]
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Dunbar, K., Valanciute, A., Lima, A., Vinuela, P. F., Jamieson, T., Rajasekaran, V., Blackmur, J., Ochocka-Fox, A.-M., Guazzelli, A., Cammareri, P., Arends, M. J., Sansom, O. J., Myant, K. B., Farrington, S. M., Dunlop, M. G., & Din, F. V. N. (2020). Aspirin rescues Wnt-driven stem-like phenotype in human intestinal organoids and increases the Wnt antagonist Dickkopf-1. Cellular and Molecular Gastroenterology and Hepatology. https://doi.org/10.1016/j.jcmgh.2020.09.010 Cite
Stimulator of interferon genes promote intestinal epithelial cells REG3γ expression to inhibit enteric infection and intestinal inflammation, thus, maintaining the intestinal homeostasis.
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Yu, Y., Yang, W., Bilotta, A. J., Yu, Y., Zhao, X., Zhou, Z., Yao, S., Xu, J., Zhou, J., Dann, S. M., Li, Y., & Cong, Y. (n.d.). STING controls intestinal homeostasis through promoting antimicrobial peptide expression in epithelial cells. The FASEB Journal, n/a(n/a). https://doi.org/10.1096/fj.202001524R Cite
Scientists investigated the role of protein tyrosine phosphatase receptor type F (PTPRF), a receptor-type tyrosine phosphatase, in regulating Wnt signaling in colorectal cancer. Knockdown of PTPRF decreased cell proliferation in patient-derived primary colon cancer cells and established colorectal cancer cell lines.
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Gan, T., Stevens, A. T., Xiong, X., Wen, Y.-A., Farmer, T. N., Li, A. T., Stevens, P. D., Golshani, S., Weiss, H. L., Mark Evers, B., & Gao, T. (2020). Inhibition of protein tyrosine phosphatase receptor type F suppresses Wnt signaling in colorectal cancer. Oncogene, 1–13. https://doi.org/10.1038/s41388-020-01472-z Cite
The authors identified a novel dual-target inhibitor, APIO-EE-07, that could block both RSK1 and MSK2 kinase activity in a dose-dependent manner. APIO-EE-07 inhibited cell growth and induced apoptosis and also increased expression of Bax as well as cleaved caspase-3 and -PARP in colon cancer cells by downregulating RSK1 and MSK2 downstream targets, including CREB and ATF1.
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Discovery of a novel dual-target inhibitor against RSK1 and MSK2 to suppress growth of human colon cancer | Oncogene. (n.d.). Retrieved September 24, 2020, from https://www.nature.com/articles/s41388-020-01467-w Cite
Hemin catalyzed the formation of reactive oxygen species (ROS) and induced oxidative DNA damage as well as DNA strand breaks in both HCEC and CRC cells. In contrast, inorganic iron hardly affected ROS levels and only slightly increased DNA damage. Hemin, but not inorganic iron, caused cell death and reduced cell viability.
[Cell Death & Disease]
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Seiwert, N., Wecklein, S., Demuth, P., Hasselwander, S., Kemper, T. A., Schwerdtle, T., Brunner, T., & Fahrer, J. (2020). Heme oxygenase 1 protects human colonocytes against ROS formation, oxidative DNA damage and cytotoxicity induced by heme iron, but not inorganic iron. Cell Death & Disease, 11(9), 1–16. https://doi.org/10.1038/s41419-020-02950-8 Cite
The authors discuss the host–microbiota interactions in colorectal cancer that have been reported so far, with particular focus on mechanisms that are linked to intestinal barrier disruption, genotoxicity and deleterious inflammation. They further comment on unknowns and on the outstanding challenges in the field, and how cutting-edge technological advances might help to overcome these.
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Researchers found that peptide YY was required in the small intestine to maintain normal electrophysiology in the presence of vasoactive intestinal polypeptide, a potent stimulator of ion secretion classically produced by enteric neurons.
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McCauley, H. A., Matthis, A. L., Enriquez, J. R., Nichol, J. T., Sanchez, J. G., Stone, W. J., Sundaram, N., Helmrath, M. A., Montrose, M. H., Aihara, E., & Wells, J. M. (2020). Enteroendocrine cells couple nutrient sensing to nutrient absorption by regulating ion transport. Nature Communications, 11(1), 4791. https://doi.org/10.1038/s41467-020-18536-z Cite