Molecular targeted therapies in hepatocellular carcinoma

Josep M. Llovet, Jordi Bruix – 26 September 2008 – Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with several genomic alterations. There is evidence of aberrant activation of several signaling cascades such as epidermal growth factor receptor (EGFR), Ras/extracellular signal‐regulated kinase, phosphoinositol 3‐kinase/mammalian target of rapamycin (mTOR), hepatocyte growth factor/mesenchymal‐epithelial transition factor, Wnt, Hedgehog, and apoptotic signaling. Recently a multikinase inhibitor, sorafenib, has shown survival benefits in patients with advanced HCC.

Ammonia impairs neutrophil phagocytic function in liver disease

Debbie L. Shawcross, Gavin A. K. Wright, Vanessa Stadlbauer, Stephen J. Hodges, Nathan A. Davies, Caroline Wheeler‐Jones, Andrew A. Pitsillides, Rajiv Jalan – 26 September 2008 – Hyperammonemia is a feature of liver failure, which is associated with increased risk of infection. The aims of the present study were to determine in vitro, in rats fed an ammoniagenic diet and in patients with cirrhosis, whether induction of hyperammonemia results in neutrophil dysfunction.

Hepatitis C virus envelope components alter localization of hepatocyte tight junction–associated proteins and promote occludin retention in the endoplasmic reticulum

Ignacio Benedicto, Francisca Molina‐Jiménez, Olga Barreiro, Alejandra Maldonado‐Rodríguez, Jesús Prieto, Ricardo Moreno‐Otero, Rafael Aldabe, Manuel López‐Cabrera, Pedro L. Majano – 26 September 2008 – Hepatocyte tight junctions (TJ) play key roles in characteristic liver functions, including bile formation and secretion. Infection by hepatitis C virus (HCV) may cause alterations of the liver architecture and disruption of the bile duct, which ultimately can lead to cholestasis. Herein, we employed the HCV replicon system to analyze the effect of HCV on TJ organization.

RNA‐binding protein insulin‐like growth factor II mRNA‐binding protein 3 expression promotes tumor invasion and predicts early recurrence and poor prognosis in hepatocellular carcinoma

Yung‐Ming Jeng, Cheng‐Chi Chang, Fu‐Chang Hu, Han‐Yi E. Chou, Hsin‐Lien Kao, Ting‐Huang Wang, Hey‐Chi Hsu – 26 September 2008 – Insulin‐like growth factor II mRNA‐binding protein 3 (IMP3) is an RNA‐binding protein expressed in embryonic tissues and multiple cancers. To investigate the role of IMP3 in hepatocellular carcinoma (HCC), its protein expression in the surgically resected unifocal tumors of 377 HCC patients (296 men and 81 women) with ages ranging from 7 to 88 years (mean, 55.49 years) was analyzed by immunohistochemistry.

Control of acute, chronic, and constitutive hyperammonemia by wild‐type and genetically engineered Lactobacillus plantarum in rodents

Charles Nicaise, Deborah Prozzi, Eric Viaene, Christophe Moreno, Thierry Gustot, Eric Quertinmont, Pieter Demetter, Valérie Suain, Philippe Goffin, Jacques Devière, Pascal Hols – 26 September 2008 – Hyperammonemia is a common complication of acute and chronic liver diseases. Often accompanied with side effects, therapeutic interventions such as antibiotics or lactulose are generally targeted to decrease the intestinal production and absorption of ammonia.

Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines

Arnhild Schrage, Katja Wechsung, Katrin Neumann, Michael Schumann, Jörg‐Dieter Schulzke, Britta Engelhardt, Martin Zeitz, Alf Hamann, Katja Klugewitz – 26 September 2008 – Transmigration through the liver endothelium is a prerequisite for the homeostatic balance of intrahepatic T cells and a key regulator of inflammatory processes within the liver. Extravasation into the liver parenchyma is regulated by the distinct expression patterns of adhesion molecules and chemokines and their receptors on the lymphocyte and endothelial cell surface.

The G protein–coupled receptor G2A: Involvement in hepatic lipid metabolism and gallstone formation in mice

Laura E. Johnson, Marc S. Elias, David T. Bolick, Marcus D. Skaflen, Richard M. Green, Catherine C. Hedrick – 26 September 2008 – The G2A receptor is a member of the ovarian cancer G protein–coupled receptor 1 family of stress‐inducible G protein–coupled receptors. In this study, we examined the hepatobiliary effects of loss of function of G2A in mice fed either a chow or lithogenic diet.

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