Targeting mitogen‐activated protein kinase kinase with the inhibitor PD0325901 decreases hepatocellular carcinoma growth in vitro and in mouse model systems

Matthew Hennig, Michele T. Yip‐Schneider, Sabrina Wentz, Huangbing Wu, S. K. Hekmatyar, Patrick Klein, Navin Bansal, C. Max Schmidt – 26 March 2010 – Hepatocellular carcinoma (HCC) is a common cause of death from solid organ malignancy worldwide. Extracellular signal‐regulated/mitogen‐activated protein kinase kinase (MEK) signaling is a critical growth regulatory pathway in HCC. Targeting MEK with a novel small molecule inhibitor, PD0325901, may inhibit HCC tumorigenesis.

Consistent beneficial effects of killer cell immunoglobulin‐like receptor 2DL3 and group 1 human leukocyte antigen‐C following exposure to hepatitis C virus

Susanne Knapp, Usama Warshow, Doha Hegazy, Louise Brackenbury, I. Neil Guha, Andrew Fowell, Ann‐Margaret Little, Graeme J. Alexander, William M.C. Rosenberg, Matthew E. Cramp, Salim I. Khakoo – 26 March 2010 – Natural killer cells are a key component in the immune control of viral infections. Their functions are controlled by inhibitory receptors for major histocompatability complex (MHC) class I, including the killer cell immunoglobulin‐like receptors (KIR).

Peginterferon alpha‐2a is associated with higher sustained virological response than peginterferon alfa‐2b in chronic hepatitis C: Systematic review of randomized trials

Tahany Awad, Kristian Thorlund, Goran Hauser, Davor Stimac, Mahasen Mabrouk, Christian Gluud – 26 March 2010 – A combination of weekly pegylated interferon (peginterferon) alpha and daily ribavirin represents the standard of care for the treatment of chronic hepatitis C according to current guidelines. It is not established which of the two licensed products (peginterferon alpha‐2a or peginterferon alfa‐2b) is most effective. We performed a systematic review of head‐to‐head randomized trials to assess the benefits and harms of the two treatments.

Portal fibroblasts: Underappreciated mediators of biliary fibrosis

Jonathan A. Dranoff, Rebecca G. Wells – 26 March 2010 – Portal fibroblasts are an important yet often overlooked nonparenchymal cell population in the liver. They are distinct from hepatic stellate cells, yet like stellate cells differentiate in the setting of chronic injury to fibrogenic myofibroblasts, playing an important role in collagen production in the fibrotic liver. Portal fibroblasts (PFs) are located adjacent to bile duct epithelia and thus play a particularly significant role in biliary fibrosis.

Twelve weeks posttreatment follow‐up is as relevant as 24 weeks to determine the sustained virologic response in patients with hepatitis C virus receiving pegylated interferon and ribavirin

Michelle Martinot‐Peignoux, Christiane Stern, Sarah Maylin, Marie‐Pierre Ripault, Nathalie Boyer, Laurence Leclere, Corinne Castelnau, Nathalie Giuily, Ahmed El Ray, Ana‐Carolina Cardoso, Rami Moucari, Tarik Asselah, Patrick Marcellin – 26 March 2010 – A sustained virologic response (SVR) in patients with chronic hepatitis C receiving pegylated interferon (PEG‐IFN) plus ribavirin is defined as undetectable serum HCV‐RNA at 24 weeks (W+24) posttreatment follow‐up. Viral load outcome in patients with virological relapse (VR) has not been explored.

Sorafenib inhibits the shedding of major histocompatibility complex class I–related chain A on hepatocellular carcinoma cells by down‐regulating a disintegrin and metalloproteinase 9

Keisuke Kohga, Tetsuo Takehara, Tomohide Tatsumi, Hisashi Ishida, Takuya Miyagi, Atsushi Hosui, Norio Hayashi – 26 March 2010 – The ectodomain of major histocompatibility complex class I–related chain A (MICA) is shed from tumor cells, and may be an important means of evading antitumor immunity. This study investigated the roles of a disintegrin and metalloproteinase 9 (ADAM9) in the shedding of MICA in human hepatocellular carcinoma (HCC).

Hepatic resection versus radiofrequency ablation for very early stage hepatocellular carcinoma: A Markov model analysis

Yun Ku Cho, Jae Kyun Kim, Wan Tae Kim, Jin Wook Chung – 26 March 2010 – No adequate randomized trials have been reported for a comparison between hepatic resection (HR) versus radiofrequency ablation (RFA) for the treatment of patients with very early stage hepatocellular carcinoma (HCC), defined as an asymptomatic solitary HCC <2 cm.

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