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.

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.

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.

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.

Gilbert syndrome redefined: A complex genetic haplotype influences the regulation of glucuronidation

Ursula Ehmer, Sandra Kalthoff, Bastian Fakundiny, Brigitte Pabst, Nicole Freiberg, Ronald Naumann, Michael P. Manns, Christian P. Strassburg – 27 December 2011 – Gilbert syndrome (GS) is characterized by intermittent unconjugated hyperbilirubinemia without structural liver damage, affecting about 10% of the white population. In GS the UGT1A1*28 variant reduces bilirubin conjugation by 70% and is associated with irinotecan and protease inhibitor side effects. The aim of this study was to characterize potential in vivo consequences of UGT1A gene variability in GS.

Zinc finger transcription factor 191, directly binding to β‐catenin promoter, promotes cell proliferation of hepatocellular carcinoma

Guoyuan Liu, Songmin Jiang, Chenji Wang, Wei Jiang, Zulong Liu, Chao Liu, Hexige Saiyin, Xianmei Yang, Suqin Shen, Deke Jiang, Ping Zhou, Dingding Han, Xiaohui Hu, Qing Yi, Long Yu – 27 December 2011 – Activation of β‐catenin, the central effector of the canonical wingless‐type (Wnt) pathway, has been implicated in hepatocellular carcinoma (HCC). However, the transcription regulation mechanism of the β‐catenin gene in HCC remains unknown. Here we report that human zinc finger protein 191 (ZNF191) is a potential regulator of β‐catenin transcription.

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