Overexpression of CXCL5 mediates neutrophil infiltration and indicates poor prognosis for hepatocellular carcinoma

Shao‐Lai Zhou, Zhi Dai, Zheng‐Jun Zhou, Xiao‐Ying Wang, Guo‐Huan Yang, Zheng Wang, Xiao‐Wu Huang, Jia Fan, Jian Zhou – 18 June 2012 – CXCL5 (epithelial neutrophil‐activating peptide‐78) is a member of a proangiogenic subgroup of the CXC‐type chemokine family of small, secreted proteins. Recently, evidence that CXCL5 is involved in carcinogenesis and cancer progression has emerged.

Protective role of V‐set and immunoglobulin domain‐containing 4 expressed on kupffer cells during immune‐mediated liver injury by inducing tolerance of liver T‐ and natural killer T‐cells

Keunok Jung, Miseon Kang, Cheol Park, Yung Hyun Choi, Youkyung Jeon, Se‐Ho Park, Su‐Kil Seo, Dan Jin, Inhak Choi – 18 June 2012 – V‐set and Ig domain‐containing 4 (VSIG4, CRIg, or Z39Ig), a newly identified B7‐related cosignaling molecule, is a complement receptor and a coinhibitory ligand that negatively regulates T‐cell immunity. Despite its exclusive expression on liver Kupffer cells (KCs) that play key roles in liver tolerance, the physiological role of VSIG4 in liver tolerance remains undefined.

The liver‐specific tumor suppressor STAT5 controls expression of the reactive oxygen species–generating enzyme NOX4 and the proapoptotic proteins PUMA and BIM in mice

Ji Hoon Yu, Bing‐Mei Zhu, Gregory Riedlinger, Keunsoo Kang, Lothar Hennighausen – 18 June 2012 – Loss of signal transducer and activator of transcription 5 (STAT5) from liver tissue results in steatosis and enhanced cell proliferation. This study demonstrates that liver‐specific Stat5‐null mice develop severe hepatic steatosis as well as hepatocellular carcinomas at 17 months of age, even in the absence of chemical insults. To understand STAT5′s role as a tumor suppressor, we identified and investigated new STAT5 target genes.

Hepatitis B virus X protein modulates oncogene yes‐associated protein by CREB to promote growth of hepatoma cells

Tao Zhang, Junping Zhang, Xiaona You, Qian Liu, Yumei Du, Yuen Gao, Changliang Shan, Guangyao Kong, Youliang Wang, Xiao Yang, Lihong Ye, Xiaodong Zhang – 18 June 2012 – Hepatitis B virus X protein (HBx) plays critical roles in the development of hepatocellular carcinogenesis (HCC). Yes‐associated protein (YAP), a downstream effector of the Hippo‐signaling pathway, is an important human oncogene. In the present article, we report that YAP is involved in the hepatocarcinogenesis mediated by HBx.

High sustained virologic response rates in rapid virologic response patients in the large real‐world PROPHESYS cohort confirm results from randomized clinical trials

Patrick Marcellin, Hugo Cheinquer, Manuela Curescu, Geoffrey M. Dusheiko, Peter Ferenci, Andrzej Horban, Donald Jensen, Gabriella Lengyel, Alessandra Mangia, Denis Ouzan, Massimo Puoti, Maribel Rodriguez‐Torres, Mitchell L. Shiffman, Manuela Schmitz, Fernando Tatsch, Mario Rizzetto – 18 June 2012 – The ability to predict which patients are most likely to achieve a sustained virologic response (SVR) with peginterferon/ribavirin would be useful in optimizing treatment for hepatitis C virus (HCV).

Identification of type I and type II interferon‐induced effectors controlling hepatitis C virus replication

Philippe Metz, Eva Dazert, Alessia Ruggieri, Johanna Mazur, Lars Kaderali, Artur Kaul, Ulf Zeuge, Marc P. Windisch, Martin Trippler, Volker Lohmann, Marco Binder, Michael Frese, Ralf Bartenschlager – 18 June 2012 – Persistent infection with hepatitis C virus (HCV) can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. All current therapies of hepatitis C include interferon‐alpha (IFN‐α). Moreover, IFN‐gamma (IFN‐γ), the only type II IFN, strongly inhibits HCV replication in vitro and is the primary mediator of HCV‐specific antiviral T‐cell responses.

Pioglitazone and vitamin E for nonalcoholic steatohepatitis: A cost utility analysis

Suzanne E. Mahady, Germaine Wong, Jonathan C. Craig, Jacob George – 18 June 2012 – Nonalcoholic steatohepatitis (NASH) is the commonest liver disease in developed countries. However, there are no current data on the cost‐effectiveness of therapeutic options such as lifestyle modification, pioglitazone, or vitamin E. We undertook a cost utility analysis to compare these strategies.

Plasmacytoid dendritic cells induce efficient stimulation of antiviral immunity in the context of chronic hepatitis B virus infection

Jeremie Martinet, Vincent Leroy, Tania Dufeu‐Duchesne, Sylvie Larrat, Marie‐Jeanne Richard, Fabien Zoulim, Joel Plumas, Caroline Aspord – 18 June 2012 – The immune control of hepatitis B virus (HBV) infection is essential for viral clearance. Therefore, restoring functional anti–HBV immunity is a promising immunotherapeutic approach to treatment of chronic infection. Plasmacytoid dendritic cells (pDCs) play a crucial role in triggering antiviral immunity through their ability to capture and process viral antigens and subsequently induce adaptive immune responses.

Promotion of liver regeneration/repair by farnesoid X receptor in both liver and intestine in mice

Lisheng Zhang, Yan‐Dong Wang, Wei‐Dong Chen, Xichun Wang, Guiyu Lou, Nian Liu, Min Lin, Barry M. Forman, Wendong Huang – 18 June 2012 – Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily and is the primary bile acid receptor. We previously showed that FXR was required for the promotion of liver regeneration/repair after physical resection or liver injury. However, the mechanism by which FXR promotes liver regeneration/repair is still unclear.

Oncogenic activation of glypican‐3 by c‐Myc in human hepatocellular carcinoma

Li Li, Ronghua Jin, Xiaoli Zhang, Fudong Lv, Lifeng Liu, Daojie Liu, Kai Liu, Ning Li, Dexi Chen – 18 June 2012 – Glypican‐3 (GPC3) is a heparan sulfate proteoglycan that has an important role in cell growth and differentiation, and its function in tumorigenesis is tissue‐dependent. In hepatocellular carcinoma (HCC), the overexpression of GPC3 has been demonstrated to be a reliable diagnostic indicator. However, the mechanisms that regulate the expression and function of GPC3 remain unclear.

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