Mycophenolic acid augments interferon‐stimulated gene expression and inhibits hepatitis C Virus infection in vitro and in vivo

Qiuwei Pan, Petra E. de Ruiter, Herold J. Metselaar, Jaap Kwekkeboom, Jeroen de Jonge, Hugo W. Tilanus, Harry L.A. Janssen, Luc J.W. van der Laan – 27 December 2011 – Mycophenolic acid (MPA) is a highly effective immunosuppressant that has broad antiviral activity against different viruses and can act in synergy with interferon‐α (IFN‐α) on hepatitis C virus (HCV) replication. MPA is a potent inosine monophosphate dehydrogenase (IMPDH) inhibitor but the antiviral mechanisms are less understood.

Hedgehog pathway activation parallels histologic severity of injury and fibrosis in human nonalcoholic fatty liver disease

Cynthia D. Guy, Ayako Suzuki, Marzena Zdanowicz, Manal F. Abdelmalek, James Burchette, Aynur Unalp, Anna Mae Diehl, for the NASH CRN – 27 December 2011 – The Hedgehog (HH)‐signaling pathway mediates several processes that are deregulated in patients with metabolic syndrome (e.g., fat mass regulation, vascular/endothelial remodeling, liver injury and repair, and carcinogenesis). The severity of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome generally correlate.

Elastin accumulation is regulated at the level of degradation by macrophage metalloelastase (MMP‐12) during experimental liver fibrosis

Antonella Pellicoro, Rebecca L. Aucott, Prakash Ramachandran, Andrew J. Robson, Jonathan A. Fallowfield, Victoria K. Snowdon, Stephen N. Hartland, Madeleine Vernon, Jeremy S. Duffield, R. Christopher Benyon, Stuart J. Forbes, John P. Iredale – 27 December 2011 – Elastin has been linked to maturity of liver fibrosis. To date, the regulation of elastin secretion and its degradation in liver fibrosis has not been characterized. The aim of this work was to define elastin accumulation and the role of the paradigm elastase macrophage metalloelastase (MMP‐12) in its turnover during fibrosis.

Amplified in breast cancer 1 enhances human cholangiocarcinoma growth and chemoresistance by simultaneous activation of Akt and Nrf2 pathways

Qiang Chen, Wenjiao Li, Yunyan Wan, Xiaochun Xia, Qiao Wu, Yanling Chen, Zhide Lai, Chundong Yu, Wengang Li – 27 December 2011 – Transcriptional coactivator amplified in breast cancer 1 (AIB1) plays important roles in the progression of several cancers such as prostate cancer, breast cancer, and hepatocellular carcinoma. However, its role in cholangiocarcinoma (CCA), a chemoresistant bile duct carcinoma with a poor prognosis, remains unclear. In this study we found that AIB1 protein was frequently overexpressed in human CCA specimens and CCA cell lines.

Synergistic inhibition of hepatocellular carcinoma growth by cotargeting chromatin modifying enzymes and poly (ADP‐ribose) polymerases

Jun‐Xiang Zhang, Da‐Qiang Li, Aiwu Ruth He, Mona Motwani, Vasilis Vasiliou, Jeyanthy Eswaran, Lopa Mishra, Rakesh Kumar – 27 December 2011 – Hepatocellular carcinoma (HCC) is a particularly lethal form of cancer, yet effective therapeutic options for advanced HCC are limited. The poly(ADP‐ribose) polymerases (PARPs) and histone deacetylases (HDACs) are emerging to be among the most promising targets in cancer therapy, and sensitivity to PARP inhibition depends on homologous recombination (HR) deficiency and inhibition of HDAC activity blocks the HR pathway.

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