Inactivation of Wnt signaling by a human antibody that recognizes the heparan sulfate chains of glypican‐3 for liver cancer therapy

Wei Gao, Heungnam Kim, Mingqian Feng, Yen Phung, Charles P. Xavier, Jeffrey S. Rubin, Mitchell Ho – 6 January 2014 – Wnt signaling is important for cancer pathogenesis and is often up‐regulated in hepatocellular carcinoma (HCC). Heparan sulfate proteoglycans (HSPGs) function as coreceptors or modulators of Wnt activation. Glypican‐3 (GPC3) is an HSPG that is highly expressed in HCC, where it can attract Wnt proteins to the cell surface and promote cell proliferation. Thus, GPC3 has emerged as a candidate therapeutic target in liver cancer.

Disruption of negative feedback loop between vasohibin‐1 and vascular endothelial growth factor decreases portal pressure, angiogenesis, and fibrosis in cirrhotic rats

Laura Coch, Marc Mejias, Annalisa Berzigotti, Ester Garcia‐Pras, Javier Gallego, Jaime Bosch, Raul Mendez, Mercedes Fernandez – 4 January 2014 – Pathological angiogenesis represents a critical hallmark for chronic liver diseases. Understanding the mechanisms regulating angiogenesis is essential to develop new therapeutic strategies that specifically target pathological angiogenesis without affecting physiological angiogenesis. Here we investigated the contribution and therapeutic impact of the endogenous angioinhibitor vasohibin‐1 in portal hypertension and cirrhosis.

Cholangiocyte senescence by way of N‐ras activation is a characteristic of primary sclerosing cholangitis

James H. Tabibian, Steven P. O'Hara, Patrick L. Splinter, Christy E. Trussoni, Nicholas F. LaRusso – 4 January 2014 – Primary sclerosing cholangitis (PSC) is an incurable cholangiopathy of unknown etiopathogenesis. Here we tested the hypothesis that cholangiocyte senescence is a pathophysiologically important phenotype in PSC. We assessed markers of cellular senescence and senescence‐associated secretory phenotype (SASP) in livers of patients with PSC, primary biliary cirrhosis, hepatitis C, and in normals by fluorescent in situ hybridization (FISH) and immunofluorescence microscopy (IFM).

Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S.

Robert J. Wong, Ramsey Cheung, Aijaz Ahmed – 25 December 2013 – Nonalcoholic steatohepatitis (NASH) is currently the third leading indication for liver transplantation (LT) in the U.S. and is predicted to become the leading indication for LT in the near future. The trends in NASH‐related hepatocellular carcinoma (HCC) among LT recipients in the U.S. remain undefined. We performed a retrospective cohort study to evaluate trends in the etiology of HCC among adult LT recipients in the U.S. from 2002 to 2012, using national data from the United Network for Organ Sharing registry.

Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S.

Robert J. Wong, Ramsey Cheung, Aijaz Ahmed – 25 December 2013 – Nonalcoholic steatohepatitis (NASH) is currently the third leading indication for liver transplantation (LT) in the U.S. and is predicted to become the leading indication for LT in the near future. The trends in NASH‐related hepatocellular carcinoma (HCC) among LT recipients in the U.S. remain undefined. We performed a retrospective cohort study to evaluate trends in the etiology of HCC among adult LT recipients in the U.S. from 2002 to 2012, using national data from the United Network for Organ Sharing registry.

Modeling viral kinetics and treatment outcome during alisporivir interferon‐free treatment in hepatitis C virus genotype 2 and 3 patients

Jeremie Guedj, Jing Yu, Micha Levi, Bin Li, Steven Kern, Nikolai V. Naoumov, Alan S. Perelson – 23 December 2013 – Alisporivir (ALV) is a cyclophilin inhibitor with pan‐genotypic activity against hepatitis C virus (HCV). Here, we characterize the viral kinetics observed in 249 patients infected with HCV genotypes 2 or 3 and treated for 6 weeks with different doses of ALV with or without ribavirin (RBV). We use this model to predict the effects of treatment duration and different doses of ALV plus RBV on sustained virologic response (SVR).

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