The survival pathways phosphatidylinositol‐3 kinase (PI3‐K)/phosphoinositide‐dependent protein kinase 1 (PDK1)/Akt modulate liver regeneration through hepatocyte size rather than proliferation

Sanae Haga, Michitaka Ozaki, Hiroshi Inoue, Yasuo Okamoto, Wataru Ogawa, Kiyoshi Takeda, Shizuo Akira, Satoru Todo – 28 December 2008 – Liver regeneration comprises a series of complicated processes. The current study was designed to investigate the roles of phosphoinositide‐dependent protein kinase 1 (PDK1)‐associated pathways in liver regeneration after partial hepatectomy (PH) using liver‐specific Pdk1‐knockout (L‐Pdk1KO) and Pdk1/STAT3 double KO (L‐DKO) mice. There was no liver regeneration, and 70% PH was lethal in L‐Pdk1KO mice.

Hepatitis B virus X protein sensitizes cells to starvation‐induced autophagy via up‐regulation of beclin 1 expression

Hong Tang, Liang Da, Yi Mao, Ying Li, Dong Li, Zhenhua Xu, Feng Li, Yifei Wang, Pierre Tiollais, Tsaiping Li, Mujun Zhao – 28 December 2008 – Human beclin 1 is the first identified mammalian gene to induce autophagy. It is commonly expressed at reduced levels in breast tumors; however, it is overexpressed in hepatitis B virus (HBV)‐infected cancerous liver tissues. To expose the possible mechanism and biological significance of this up‐regulation of beclin 1, we investigated the regulation of beclin 1 expression by HBV x protein (HBx) in hepatic or hepatoma cell lines.

Effect of polyI:C cotreatment on halothane‐induced liver injury in mice

Linling Cheng, Qiang You, Hao Yin, Michael Holt, Christopher Franklin, Cynthia Ju – 28 December 2008 – Drug‐induced liver injury (DILI) is a challenging problem in drug development and clinical practice. Patient susceptibility to DILI is multifactorial, making these reactions difficult to predict and prevent. Clinical observations have suggested that concurrent bacterial and viral infections represent an important risk factor in determining patient susceptibility to developing adverse drug reactions, although the underlying mechanism is not clear.

Competitive inhibition of leptin signaling results in amelioration of liver fibrosis through modulation of stellate cell function

Eran Elinav, Mohammad Ali, Rafi Bruck, Eli Brazowski, Adam Phillips, Yami Shapira, Meirav Katz, Gila Solomon, Zamir Halpern, Arieh Gertler – 28 December 2008 – Leptin signaling is involved in T‐cell polarization and is required for profibrotic function of hepatic stellate cells (HSCs). Leptin‐deficient ob/ob mice do not develop liver fibrosis despite the presence of severe long‐standing steatohepatitis.

A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma

Daniel H. Palmer, Rachel S. Midgley, Noweeda Mirza, Elizabeth E. Torr, Forhad Ahmed, Jane C. Steele, Neil M. Steven, David J. Kerr, Lawrence S. Young, David H. Adams – 28 December 2008 – This is a phase II clinical trial investigating the safety and efficacy of intravenous vaccination with mature autologous dendritic cells (DCs) pulsed ex vivo with a liver tumor cell line lysate (HepG2) in patients with advanced hepatocellular carcinoma (HCC).

Atorvastatin prevents carbohydrate response element binding protein activation in the fructose‐fed rat by activating protein kinase A

Ricardo Rodríguez‐Calvo, Emma Barroso, Lucía Serrano, Teresa Coll, Rosa M. Sánchez, Manuel Merlos, Xavier Palomer, Juan C. Laguna, Manuel Vázquez‐Carrera – 28 December 2008 – High fructose intake contributes to the overall epidemic of obesity and metabolic disease. Here we examined whether atorvastatin treatment blocks the activation of the carbohydrate response element binding protein (ChREBP) in the fructose‐fed rat.

Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population‐based study of U.S. veterans

Hashem B. El‐Serag, Eric A. Engels, Ola Landgren, Elizabeth Chiao, Louise Henderson, Harshinie C. Amaratunge, Thomas P. Giordano – 28 December 2008 – Hepatitis C virus (HCV) may increase the risk of hepatopancreaticobiliary tumors other than hepatocellular carcinoma (HCC). Previous case control studies indicated a possible association between HCV and intrahepatic cholangiocarcinoma (ICC). Little is known about the association between HCV and extrahepatic cholangiocarcinoma (ECC) or pancreatic cancer.

Diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with alcoholic liver disease

Sylvie Naveau, Guillaume Gaudé, Amani Asnacios, Hélène Agostini, Annie Abella, Nadège Barri‐Ova, Barbara Dauvois, Sophie Prévot, Yen Ngo, Mona Munteanu, Axel Balian, Micheline Njiké‐Nakseu, Gabriel Perlemuter, Thierry Poynard – 28 December 2008 – FibroTest has been validated as a biomarker of fibrosis in patients with chronic viral hepatitis, with a similar prognostic value as biopsy. The aim of the study was to compare the diagnostic and prognostic values of FibroTest versus the recently patented biomarkers, FibrometerA, and Hepascore.

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