News From The Journal Of Clinical Investigation: Jan. 17, 2012

Main Category: Liver Disease / Hepatitis
Also Included In: Cancer / Oncology;  Urology / Nephrology
Article Date: 18 Jan 2012 - 2:00 PST

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VIROLOGY: How to prevent hepatitis B virus reproducing

Infection with hepatitis B virus (HBV) is a major health problem worldwide, despite the fact that a highly effective preventative vaccine exists. A modified form of the immune molecule IFN-alpha is commonly used to treat individuals infected with HBV. The rationale behind this is that IFN-alpha inhibits HBV replication in vivo and in vitro, although the mechanisms by which it does this have not been clearly defined. A team of researchers - led by Maura Dandri, at University Medical Hospital Hamburg-Eppendorf, Germany; and Massimo Levrero, at Sapienza University, Italy - has now identified a new mechanism by which IFN-alpha suppresses HBV replication in vitro and in vivo. The authors hope that this new insight could help in the development of new approaches to treat individuals infected with HBV.

TITLE: IFN-alpha inhibits HBV transcription and replication in cell culture and in humanized mice by targeting the epigenetic regulation of the nuclear cccDNA minichromosome

View this article at: http://www.jci.org/articles/view/58847?key=3a5c4549350a2300311e

ONCOLOGY: Modulating the inflammatory environment in liver cancer modifies outcome

Hepatocellular carcinoma (HCC) is the most common form of liver cancer and the third leading cause of cancer-related death worldwide. In most cases, HCC develops after a sustained period of inflammation in the liver, for example as a result of alcoholism or infection with hepatitis C virus. Genetic mutations that activate the signaling molecule beta-catenin are seen in a subset of HCCs, and individuals with these tumors have a better prognosis. A team of researchers, led by Mireille Viguier and Christine Perret, at the Institut Cochin, Paris, has now generated data in mice that provide a potential molecular explanation for this.

Viguier, Perret, and colleagues found that activation of beta-catenin signaling modulates the inflammatory environment to control tumor development. Specifically, beta-catenin signaling was shown to activate both pro- and anti-inflammatory molecules. The resulting inflammatory environment, while permissive for tumor development also contained components that somewhat restrained tumor development and spread to distant sites. Detailed analysis of these restraining components identified potential new targets for immunotherapeutic approaches to treating patients with HCC.

TITLE: Oncogenic beta-catenin triggers an inflammatory response that determines the aggressiveness of hepatocellular carcinoma in mice

View this article at: http://www.jci.org/articles/view/43937?key=745e8aa8846e5f104b79

NEPHROLOGY: Maintaining integrity in the kidney

A central function of our kidneys is to filter waste from our blood and to divert it into our urine. Specialized cells known as podocytes are key to the integrity of the filtration barrier. Many kidney diseases are characterized by abnormal function of the filtration barrier, which occurs because podocyte morphology (structure) is altered. Such diseases are known as glomerular diseases. A team of researchers led by Lawrence Holzman, at the University of Pennsylvania, Philadelphia, has now identified a molecular pathway involved in the alterations to podocyte morphology observed in mouse models of glomerular disease. They team suggest that inhibitors of molecules in this signaling pathway, for example inhibitors of the FAK-Cas-Crk protein complex, might help prevent the podocyte structural changes associated with glomerular diseases.

TITLE: Crk1/2-dependent signaling is necessary for podocyte foot process spreading in mouse models of glomerular disease

View this article at: http://www.jci.org/articles/view/60070?key=26e460af554f691c1702

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