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).

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.

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.

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.

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.

Modeling complex decay profiles of hepatitis B virus during antiviral therapy

Harel Dahari, Emi Shudo, Ruy M. Ribeiro, Alan S. Perelson – 28 December 2008 – Typically, hepatitis B virus (HBV) decays in patients under therapy in a biphasic manner. However, more complex decay profiles of HBV DNA (e.g., flat partial response, triphasic, and stepwise), for which we have no clear understanding, have also been observed in some treated patients.

Telithromycin‐associated hepatotoxicity: Clinical spectrum and causality assessment of 42 cases

Allen D. Brinker, Ronald T. Wassel, Jenna Lyndly, Jose Serrano, Mark Avigan, William M. Lee, Leonard B. Seeff – 28 December 2008 – Telithromycin is the first of a new class of ketolide antibiotics with increased activity against penicillin‐resistant and erythromycin‐resistant pneumococci. This agent received approval by the United States Food and Drug Administration (FDA) in 2004 for treatment of upper and lower respiratory infections. Following market introduction, spontaneous reports of telithromycin‐associated hepatotoxicity, including frank liver failure, were received.

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