Targeting heat shock protein 90 with non‐quinone inhibitors: A novel chemotherapeutic approach in human hepatocellular carcinoma

Marco Breinig, Eloisi Caldas‐Lopes, Benjamin Goeppert, Mona Malz, Ralf Rieker, Frank Bergmann, Peter Schirmacher, Matthias Mayer, Gabriela Chiosis, Michael André Kern – 23 June 2009 – The inhibition of heat shock protein 90 (Hsp90) has emerged as a promising antineoplastic strategy in diverse human malignancies. Hsp90 has been predicted to be involved in hepatocellular carcinoma (HCC) development; however, its role in hepatocarcinogenesis remains elusive.

Toll‐like receptor 3 signaling attenuates liver regeneration

Elina Zorde‐Khvalevsky, Rinat Abramovitch, Hila Barash, Irit Spivak‐Pohis, Ludmila Rivkin, Jacob Rachmilewitz, Eithan Galun, Hilla Giladi – 23 June 2009 – The current model for liver regeneration suggests that cell damage triggers Toll‐like receptor (TLR) signaling via MyD88, leading to the induction of nuclear factor κB (NF‐κB) and secretion of inflammatory cytokines that in turn prime liver regeneration.

Inhibiting glycosphingolipid synthesis ameliorates hepatic steatosis in obese mice

Hongmei Zhao, Malgorzata Przybylska, I‐Huan Wu, Jinhua Zhang, Panagiotis Maniatis, Joshua Pacheco, Peter Piepenhagen, Diane Copeland, Cynthia Arbeeny, James A. Shayman, Johannes M. Aerts, Canwen Jiang, Seng H. Cheng, Nelson S. Yew – 23 June 2009 – Steatosis in the liver is a common feature of obesity and type 2 diabetes and the precursor to the development of nonalcoholic steatohepatitis (NASH), cirrhosis, and liver failure. It has been shown previously that inhibiting glycosphingolipid (GSL) synthesis increases insulin sensitivity and lowers glucose levels in diabetic rodent models.

Chromodomain helicase/adenosine triphosphatase DNA binding protein 1–like (CHD1l) gene suppresses the nucleus‐to‐mitochondria translocation of nur77 to sustain hepatocellular carcinoma cell survival

Leilei Chen, Liang Hu, Tim Hon Man Chan, George Sai‐Wah Tsao, Dan Xie, Ke‐Ke Huo, Li Fu, Stephanie Ma, Bo‐Jian Zheng, Xin‐Yuan Guan – 23 June 2009 – Amplification of 1q21 has been detected in 58% to 78% of primary hepatocellular carcinoma cases, suggesting that one or more oncogenes within the amplicon play a critical role in the development of this disease. The chromodomain helicase/adenosine triphosphatase DNA binding protein 1–like gene (CHD1L) is a recently identified oncogene localized at 1q21.

L‐ornithine phenylacetate attenuates increased arterial and extracellular brain ammonia and prevents intracranial hypertension in pigs with acute liver failure

Lars Marius Ytrebø, Rune Gangsøy Kristiansen, Hanne Mæhre, Ole Martin Fuskevåg, Trine Kalstad, Arthur Revhaug, María Jover Cobos, Rajiv Jalan, Christopher F. Rose – 23 June 2009 – Hyperammonemia is a feature of acute liver failure (ALF), which is associated with increased intracranial pressure (ICP) and brain herniation.

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