SummaryThe serum and glucocorticoid inducible kinase SGK1 was originally cloned from mammary tumor cells. SGK1 was found to be upregulated in a variety of tumors, but down-regulated in several distinct tumors. Thus, evidence for a role of SGK1 in tumor growth remained conflicting. According to in vitro observations, SGK1 is upregulated by the oncogene b-catenin and negatively regulates the proapoptotic transcription factor FOXO3a, which in turn stimulates transcription of the Bcl2-interacting mediator BIM. This study aimed to define the role of SGK1 in colon carcinoma in vivo. SGK1 knockout mice (sgk1 2/2 ) and their wild type littermates (sgk1 1/1 ) were subjected to chemical cancerogenesis (intraperitoneal injection of 20 mg/kg 1,2-dimethylhydrazine followed by three cycles of 30 g/L synthetic dextran sulfate sodium for 7 days). Moreover, SGK1 was silenced in HEK293 cells. FOXO3a and BIM protein abundance was determined by Western blotting and immunohistochemistry. Following chemical cancerogenesis, sgk1 2/2 mice developed significantly less colonic tumors than sgk1 1/1 mice. According to Western blotting and immunohistochemistry, SGK1 deficiency enhanced the expression of FOXO3a and BIM both, in vitro and in vivo. SGK1 deficiency counteracts the development of colonic tumors, an effect at least in part due to up-regulation of FOXO3a and BIM.2009 IUBMB IUBMB Life, 61 (7): [768][769][770][771][772][773][774][775][776] 2009
Metastatic melanoma is notorious for its immune evasion and resistance to conventional chemotherapy. The recent success of ipilimumab, a human monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), in increasing the median survival time and stabilizing the disease progression renewed, hopes in treatment for melanoma. Currently, ipilimumab and high-dose interleukin-2 (IL-2; Aldesleukin) are approved as monotherapies for the treatment of patients with unresectable advanced melanoma, and pegylated interferon-α2b (p-IFN-α2b) is approved as an adjuvant for the treatment of patients with surgically resected high-risk melanoma. The present review describes the currently approved immune-modulators and the promising immune-based interventions that are currently in clinical trials. We present the four commonly used strategies to boost immune responses against the tumors; monoclonal antibodies, cytokines, cancer vaccines, and adoptive T cell transfer. The corresponding lists of ongoing clinical trials include details of the trial phase, target patients, intervention details, status of the study, and expected date of completion. Further, our review discusses the challenges faced by immunotherapy and the various strategies adopted to overcome them.
Background/Aims: Gum arabic (GA) is a Ca2+-, Mg2+- and K+-rich dietary fiber used for the treatment of patients with chronic kidney disease in Middle Eastern countries. In healthy mice, GA treatment increases creatinine clearance, renal ADH excretion, as well as intestinal and renal excretion of Mg2+ and Ca2+. GA decreases plasma Pi concentration, urinary Pi and Na+ excretion. The present study explored the effects of GA on renal function in diabetic mice. Methods: Metabolic cage experiments were performed on Akita mice (akita+/–), which spontaneously develop insulin deficiency and thus hyperglycemia. Plasma and urinary concentrations of Na+, K+ and Ca2+ were measured by flame photometry (AFM 5051, Eppendorf, Germany), creatinine by the Jaffé method, phosphate photometrically, urea by an enzymatic method, glucose utilizing a glucometer and an enzymatic kit, aldosterone using an RIA, urinary albumin fluorometrically, and blood pressure by the tail-cuff method. Results: GA (10% in drinking water) significantly increased urinary excretion of Ca2+ and significantly decreased plasma phosphate and urea concentrations, urinary flow rate, urinary Na+, phosphate and glucose excretion, blood pressure and proteinuria. Conclusions: GA treatment decreases blood pressure and proteinuria in diabetic mice and may thus prove beneficial in diabetic nephropathy.
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