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In recent years, immune checkpoint inhibitors (ICPI) have become established as an integral part of drug tumor therapy. They belong to a group of monoclonal antibodies that promote anti-cancer cell immune response. Inhibitory signaling pathways are interrupted by binding to CTLA-4 and PD-1 or PD-L1, which increases the activity of cytotoxic T lymphocytes and reduces the immunological tolerance to tumor cells.Diarrhea - a symptom of enterocolitis - is the most common side effect of ICPI therapy after dermatological phenomena. A combined CTLA-4 and PD-1 blockade may affect up to 44 % of patients. The symptoms of ICPI-associated colitis are similar to the clinical appearance of inflammatory bowel disease.The treatment of affected patients should follow a standardized approach. Both the European and American Oncology Societies offer specific recommendations for the diagnosis and treatment of ICPI-associated adverse reactions. Rapid immunosuppressant treatments, to include steroids and biologics, are necessary to reduce morbidity once differential diagnoses are excluded. It may then be possible to subsequently resume ICPI therapy.Immune-mediated hepatitis is a potential side effect which occurs about 6 to 14 weeks after initiation of therapy. It is usually asymptomatic and characterized by an increase in serum transaminases. Lipasemia, without clinical signs of acute pancreatitis, is a common laboratory finding, which usually has no therapeutic consequence., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Cancer stem cells (CSC) are associated with tumor resistance and are characterized in gastric cancer (GC). Studies have indicated that Notch and wnt-beta-catenin pathways are crucial for CSC development. Using CD44 + CSCs, we investigated the role of these pathways in GC carcinogenesis. We performed cell proliferation, wound healing, invasion, tumorsphere, and apoptosis assays. Immunoblot analysis of downstream signaling targets of Notch and wnt-beta-catenin were tested after gamma-secretase inhibitor IX (GSI) treatment. Immunohistochemistry, immunofluorescence, and Fluorescence activated cell sorting (FACS) were used to determine CD44 and Hairy enhancer of split-1 (Hes1) expression in human GC tissues. CD44 + CSCs were subcutaneously injected into NMR-nu/nu mice and treated with vehicle or GSI. GC patients with expression of CD44 and Hes1 showed overall reduced survival. CD44 + CSCs showed high expression of Hes1. GSI treatment showed effective inhibition of cell proliferation, migration, invasion, tumor sphere formation of CD44 + CSCs, and induced apoptosis. Importanly, Notch1 was found to be important in mediating a crosstalk between Notch and wnt-beta-catenin in CD44 + CSCs. Our study highlights a crosstalk between Notch and wnt-beta-catenin in gastric CD44 + CSCs. Expression of CD44 and Hes1 is associated with patient overall survival. GSI could be an alternative drug to treat GC. Stem Cells Translational Medicine 2017;6:819-829., (© 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)