To identify the genes responsible for carcinogenesis and progression of hepatocellular carcinoma (HCC), we screened differentially expressed genes in several human HCC cell lines. Among these genes, Gpr49 was up-regulated in PLC/PRF/5 and HepG2. Gpr49 is a member of the glycoprotein hormone receptor subfamily, which includes the thyroid-stimulating hormone receptor (TSHR). However, Gpr49 remains to be an orphan G-protein-coupled receptor. H epatocellular carcinoma (HCC) is one of the most common tumors worldwide, and its incidence is unlikely to be reduced in the near future in spite of much effort. In the geographic areas in which the incidence of HCC is high, it occurs most frequently after chronic liver disease resulting from hepatitis virus infection. 1 Therefore, development of antiviral therapy is expected to contribute significantly to a decrease in the incidence of HCC. At the same time, it is very important to elucidate the molecular mechanisms of hepatocarcinogenesis and develop specific measures for prevention. Various genetic alterations in HCC have been reported, but much remains unknown. We have attempted to elucidate gene alterations in HCC by using mRNA differential display polymerase chain reaction (mRNA DD-PCR) to investigate the differences in mRNA expression in HCC cell lines. For example, we successfully cloned DRH1 as a novel molecule down-regulated in advanced HCC, 2 although the direct role of DRH1 in the progression of HCC has not been elucidated.We report here that Gpr49, 3,4 which belongs to the glycoprotein hormone receptor subfamily, is markedly up-regulated in HCCs carrying ␤-catenin mutations. It has recently been established that ␤-catenin is involved in carcinogenesis through activation of the Wnt-signaling pathway, 5 and that several genes, such as c-myc and cyclin D1, are the downstream targets in this pathway. 6-8 Our result suggests that Gpr49 is one of these downstream genes. Materials and MethodsPatients and Cell Lines. We analyzed 38 primary HCCs and their corresponding noncancerous liver tissues

In distal pancreatectomy for the non-fibrotic pancreas, ultrasonic dissection without suture closure of the stump reduced the incidence of pancreatic fistula compared with conventional division and suture, in this randomized trial.

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Background. Prediction and prevention of hepatitis B virus (HBV)-related

Severe influenza is characterized by cytokine storm and multiorgan failure with metabolic energy disorders and vascular hyperpermeability. In the regulation of energy homeostasis, the pyruvate dehydrogenase (PDH) complex plays an important role by catalyzing oxidative decarboxylation of pyruvate, linking glycolysis to the tricarboxylic acid cycle and fatty acid synthesis, and thus its activity is linked to energy homeostasis. The present study tested the effects of diisopropylamine dichloroacetate (DADA), a new PDH kinase 4 (PDK4) inhibitor, in mice with severe influenza. Infection of mice with influenza A PR/8/34(H1N1) virus resulted in marked down-regulation of PDH activity and ATP level, with selective up-regulation of PDK4 in the skeletal muscles, heart, liver and lungs. Oral administration of DADA at 12-h intervals for 14 days starting immediately after infection significantly restored PDH activity and ATP level in various organs, and ameliorated disorders of glucose and lipid metabolism in the blood, together with marked improvement of survival and suppression of cytokine storm, trypsin up-regulation and viral replication. These results indicate that through PDK4 inhibition, DADA effectively suppresses the host metabolic disorder-cytokine cycle, which is closely linked to the influenza virus-cytokine-trypsin cycle, resulting in prevention of multiorgan failure in severe influenza.