Adenovirus-mediated overexpression of RORα (Ad-RORα) or treatment with the RORα activator, SR1078, reduced aerobic glycolysis and down-regulated biosynthetic pathways in hepatoma cells. Ad-RORα and SR1078 reduced the expression

of pyruvate dehydrogenase kinase 2 (PDK2) and inhibited the phosphorylation of PDHe1α, subsequently shifted pyruvate to complete oxidation. The RORα-mediated decrease in PDK2 levels was caused by up-regulation of p21 rather than p53. Furthermore, RORα inhibited hepatoma growth both in vitro and in a xenograft model in vivo. We also found that suppression of PDK2 inhibited hepatoma growth in a xenograft model. These findings mimic the altered glucose utilization and GDC-973 hepatoma growth caused by glutamine deprivation. Finally, tumor tissue from 187 hepatocellular carcinoma patients expressed lower levels of RORα than adjacent non-tumor tissue, supporting a potential beneficial effect of RORα activation in the treatment of liver cancer. Conclusion: The data reported herein show that RORα mediates reprogramming of glucose metabolism in hepatoma cells in response to glutamine deficiency. The relationships established here between glutamine AZD2281 ic50 metabolism, RORα expression and signaling, and aerobic glycolysis have

implications for therapeutic targeting of liver cancer metabolism. (Hepatology 2014) “
“Background and Aim:  Gastric fundus perforation is a serious complication of endoscopic mucosal resection and endoscopic submucosal dissection performed for the removal of early gastric cancers or subepithelial tumors. The novel over-the-scope MCE公司 clip (OTSC) has recently been found to be effective for closing gastrointestinal-tract perforations and accesses for natural orifice transluminal endoscopic surgery. However, feasibility studies of OTSCs in gastric fundus perforation are still lacking. The aim of this study was therefore to demonstrate the feasibility of endoscopic closure of gastric fundus perforation using the OTSC system in a dog model. Methods:  Gastric fundus

perforations were created by needle-knife electrocautery in seven dogs. The perforations were then closed using the OTSC clipping system. Stomach distension was maintained by maximum insufflation with air and methylene blue solution (500 mL) was instilled to submerge the closed perforation. Leaks were detected laparoscopically. Results:  Perforations were closed in all seven cases with a mean time of 18.5 ± 6.4 min (11–28 min). Twin Grasper assistance failed to release the OTSCs in two of the seven cases (2/7, 28.6%) because of difficulties associated with the J-maneuver (retroflexion of endoscope) required for the gastric fundus procedure, and OTCS were forced into place by suction. Minor leakage was observed in one case (1/7, 14.3%). No damages related to the clip system were found during postmortem examinations.