Patatin‐like phospholipase domain‐containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease

Weiqin Chen, Benny Chang, Lan Li, Lawrence Chan – 26 August 2010 – PNPLA3 (adiponutrin), a novel patatin‐like phospholipase domain‐containing enzyme, is expressed at high level in fat, but also in other tissues including liver. Polymorphisms in PNPLA3 have been linked to obesity and insulin sensitivity. Notably, a nonsynonymous variant rs738409(G) allele of the PNPLA3 gene was found to be strongly associated with both nonalcoholic and alcoholic fatty liver disease. We have generated Pnpla3−/− mice by gene targeting.

Preclinical assessment of simultaneous targeting of epidermal growth factor receptor (ErbB1) and ErbB2 as a strategy for cholangiocarcinoma therapy

Zichen Zhang, Regina A. Oyesanya, Deanna J. W. Campbell, Jorge A. Almenara, Jennifer L. DeWitt, Alphonse E. Sirica – 26 August 2010 – Overexpression of epidermal growth factor receptor (ErbB1) and/or ErbB2 has been implicated in the pathogenesis of cholangiocarcinoma, suggesting that combined ErbB1/ErbB2 targeting might serve as a target‐based therapeutic strategy for this highly lethal cancer.

Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease

Brent A. Neuschwander‐Tetri, Jeanne M. Clark, Nathan M. Bass, Mark L. Van Natta, Aynur Unalp‐Arida, James Tonascia, Claudia O. Zein, Elizabeth M. Brunt, David E. Kleiner, Arthur J. McCullough, Arun J. Sanyal, Anna Mae Diehl, Joel E. Lavine, Naga Chalasani, Kris V. Kowdley, NASH Clinical Research Network – 26 August 2010 – The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) was formed to conduct multicenter studies on the etiology, contributing factors, natural history, and treatment of nonalcoholic steatohepatitis (NASH).

Transforming growth factor‐beta induces senescence in hepatocellular carcinoma cells and inhibits tumor growth

Serif Senturk, Mine Mumcuoglu, Ozge Gursoy‐Yuzugullu, Burcu Cingoz, Kamil Can Akcali, Mehmet Ozturk – 26 August 2010 – Senescence induction could be used as an effective treatment for hepatocellular carcinoma (HCC). However, major senescence inducers (p53 and p16Ink4a) are frequently inactivated in these cancers. We tested whether transforming growth factor‐β (TGF‐β) could serve as a potential senescence inducer in HCC. First, we screened for HCC cell lines with intact TGF‐β signaling that leads to small mothers against decapentaplegic (Smad)‐targeted gene activation.

PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease

Elizabeth K. Speliotes, Johannah L. Butler, Cameron D. Palmer, Benjamin F. Voight, the GIANT Consortium the MIGen Consortium, the NASH CRN, Joel N. Hirschhorn – 26 August 2010 – Single nucleotide polymorphisms (SNPs) near 7 loci have been associated with liver function tests or with liver steatosis by magnetic resonance spectroscopy. In this study we aim to test whether these SNPs influence the risk of histologically‐confirmed nonalcoholic fatty liver disease (NAFLD).

Deleterious effects of beta‐blockers on survival in patients with cirrhosis and refractory ascites

Thomas Sersté, Christian Melot, Claire Francoz, François Durand, Pierre‐Emmanuel Rautou, Dominique Valla, Richard Moreau, Didier Lebrec – 26 August 2010 – Beta‐blockers may have a negative impact on survival in patients with cirrhosis and refractory ascites. The aim of this study was to evaluate the effect of the administration of beta‐blockers on long‐term survival in patients with cirrhosis and refractory ascites.

The association of genetic variability in patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease

Yaron Rotman, Christopher Koh, Joseph M. Zmuda, David E. Kleiner, T. Jake Liang, the NASH CRN – 26 August 2010 – Genome‐wide association studies identified single‐nucleotide polymorphisms (SNPs) that are associated with increased hepatic fat or elevated liver enzymes, presumably reflecting nonalcoholic fatty liver disease (NAFLD).

Direct activation of forkhead box O3 by tumor suppressors p53 and p73 is disrupted during liver regeneration in mice

Svitlana Kurinna, Sabrina A. Stratton, Wen‐Wei Tsai, Kadir C. Akdemir, Weisong Gu, Pallavi Singh, Triona Goode, Gretchen J. Darlington, Michelle Craig Barton – 26 August 2010 – The p53 family of proteins regulates the expression of target genes that promote cell cycle arrest and apoptosis, which may be linked to cellular growth control as well as tumor suppression. Within the p53 family, p53 and the transactivating p73 isoform (TA‐p73) have hepatic‐specific functions in development and tumor suppression.

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