Treatment response in the PIVENS trial is associated with decreased hedgehog pathway activity

Cynthia D. Guy, Ayako Suzuki, Manal F. Abdelmalek, James L. Burchette, Anna Mae Diehl, for the NASH CRN – 22 May 2014 – Hedgehog (Hh) ligand production by ballooned hepatocytes drives nonalcoholic steatohepatitis (NASH) progression in mice. The NIDDK‐sponsored PIVENS trial (NCT00063622) showed that vitamin E (VitE) improved NASH. We investigated whether VitE treatment and improvement in NASH were associated with changes in Hh pathway activity.

Autocrine vascular endothelial growth factor signaling promotes cell proliferation and modulates sorafenib treatment efficacy in hepatocellular carcinoma

Sui Peng, Ye Wang, Hong Peng, Dong Chen, Shunli Shen, Baogang Peng, Minhu Chen, Riccardo Lencioni, Ming Kuang – 22 May 2014 – Tumor cells express vascular endothelial growth factor (VEGF) that can activate VEGF receptors (VEGFRs) on or within tumor cells to promote growth in an angiogenesis‐independent fashion; however, this autocrine VEGF pathway has not been reported in hepatocellular carcinoma (HCC). Sorafenib, an angiogenic inhibitor, is the only drug approved for use in advanced HCC patients. Yet the treatment efficacy is diverse and the mechanism behind it remains undetermined.

Etanercept blocks inflammatory responses orchestrated by TNF‐α to promote transplanted cell engraftment and proliferation in rat liver

Preeti Viswanathan, Sorabh Kapoor, Vinay Kumaran, Brigid Joseph, Sanjeev Gupta – 21 May 2014 – Engraftment of transplanted cells is critical for liver‐directed cell therapy, but most transplanted cells are rapidly cleared from liver sinusoids by proinflammatory cytokines/chemokines/receptors after activation of neutrophils or Kupffer cells (KCs). To define whether tumor necrosis factor alpha (TNF‐α) served roles in cell‐transplantation–induced hepatic inflammation, we used the TNF‐α antagonist, etanercept (ETN), for studies in syngeneic rat hepatocyte transplantation systems.

Dual role of B7 costimulation in obesity‐related nonalcoholic steatohepatitis and metabolic dysregulation

Antonios Chatzigeorgiou, Kyoung‐Jin Chung, Ruben Garcia‐Martin, Vasileia‐Ismini Alexaki, Anne Klotzsche‐von Ameln, Julia Phieler, David Sprott, Waldemar Kanczkowski, Theodora Tzanavari, Mohktar Bdeir, Sibylle Bergmann, Marc Cartellieri, Michael Bachmann, Polyxeni Nikolakopoulou, Andreas Androutsellis‐Theotokis, Gabriele Siegert, Stefan R. Bornstein, Michael H. Muders, Louis Boon, Katia P.

Shotgun proteomics: Identification of unique protein profiles of apoptotic bodies from biliary epithelial cells

Ana Lleo, Weici Zhang, W. Hayes McDonald, Erin H. Seeley, Patrick S.C. Leung, Ross L. Coppel, Aftab A. Ansari, David H. Adams, Simon Afford, Pietro Invernizzi, M. Eric Gershwin – 20 May 2014 – Shotgun proteomics is a powerful analytic method to characterize complex protein mixtures in combination with multidimensional liquid chromatography‐tandem mass spectrometry (LC‐MS/MS).

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