The immunosuppressive pipeline: Meeting unmet needs in liver transplantation

Nazia Selzner, David R. Grant, Itay Shalev, Gary A. Levy – 28 September 2010 – Liver transplantation is now recognized as the treatment of choice for end‐stage liver failure. Its success can be attributed largely to the generation of selective immunosuppressive agents, which have resulted in a dramatic reduction in the incidence of acute rejection and improvements in the short‐ and long‐term outcomes of patients.

Tumor necrosis factor α sensitizes primary murine hepatocytes to Fas/CD95‐induced apoptosis in a Bim‐ and Bid‐dependent manner

Kathrin Schmich, Rebekka Schlatter, Nadia Corazza, Karine Sá Ferreira, Michael Ederer, Thomas Brunner, Christoph Borner, Irmgard Merfort – 24 September 2010 – Fas/CD95 is a critical mediator of cell death in many chronic and acute liver diseases and induces apoptosis in primary hepatocytes in vitro. In contrast, the proinflammatory cytokine tumor necrosis factor α (TNFα) fails to provoke cell death in isolated hepatocytes but has been implicated in hepatocyte apoptosis during liver diseases associated with chronic inflammation.

C‐reactive protein impairs hepatic insulin sensitivity and insulin signaling in rats: Role of mitogen‐activated protein kinases

Liang Xi, Changting Xiao, Robert H.J. Bandsma, Mark Naples, Khosrow Adeli, Gary F. Lewis – 24 September 2010 – Plasma C‐reactive protein (CRP) concentration is increased in the metabolic syndrome, which consists of a cluster of cardiovascular disease risk factors, including insulin resistance. It is not known, however, whether CRP is merely a marker of accompanying inflammation or whether it contributes causally to insulin resistance. The objective of this study is to investigate the role that CRP may play in the development of insulin resistance.

Adipose triglyceride lipase is a major hepatic lipase that regulates triacylglycerol turnover and fatty acid signaling and partitioning

Kuok Teong Ong, Mara T. Mashek, So Young Bu, Andrew S. Greenberg, Douglas G. Mashek – 24 September 2010 – Despite advances in our understanding of the ways in which nutrient oversupply and triacylglycerol (TAG) anabolism contribute to hepatic steatosis, little is known about the lipases responsible for regulating hepatic TAG turnover. Recent studies have identified adipose triglyceride lipase (ATGL) as a major lipase in adipose tissue, although its role in the liver is largely unknown. Thus, we tested the contribution of ATGL to hepatic lipid metabolism and signaling.

Antihepatoma activity of chaetocin due to deregulated splicing of hypoxia‐inducible factor 1α pre‐mRNA in mice and in vitro

Yoon‐Mi Lee, Ji‐Hong Lim, Haejin Yoon, Yang‐Sook Chun, Jong‐Wan Park – 24 September 2010 – Chaetocin, an antibiotic produced by Chaetomium species fungi, was recently found to have antimyeloma activity. Here we examined whether chaetocin has anticancer activities against solid tumors. Chaetocin inhibited the growth of mouse and human hepatoma grafts in nude mice. Immunohistochemical analyses revealed that chaetocin inhibits hypoxia‐inducible factor‐1α (HIF‐1α) expression and vessel formation in the tumors.

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