Combined endostatin/sFlt‐1 antiangiogenic gene therapy is highly effective in a rat model of HCC

Florian Graepler, Barbara Verbeek, Tilmann Graeter, Irina Smirnow, Hwai Loong Kong, Detlef Schuppan, Michael Bauer, Reinhard Vonthein, Michael Gregor, Ulrich M. Lauer – 28 February 2005 – Hepatocellular carcinoma (HCC) is regarded as a suitable target for antiangiogenic strategies. However, antiangiogenic agents aimed at single targets can be neutralized by upregulation of other proangiogenic factors. Therefore, combined approaches addressing at least two angiogenic targets should be more effective.

Antiviral efficacy of NS3‐serine protease inhibitor BILN‐2061 in patients with chronic genotype 2 and 3 hepatitis C

Markus Reiser, Holger Hinrichsen, Yves Benhamou, Henk W. Reesink, Heiner Wedemeyer, Cristina Avendano, Neus Riba, Chan‐Loi Yong, Gerhard Nehmiz, Gerhard G. Steinmann – 24 February 2005 – BILN‐2061, a specific and potent peptidomimetic inhibitor of the HCV NS3 protease, has recently been shown to markedly lower serum hepatitis C virus (HCV)‐RNA levels in patients chronically infected with HCV genotype 1 in three 2‐day proof of principle studies. The aim of the current study was to assess the antiviral efficacy of BILN‐2061 in patients with genotypes 2 and 3 HCV infection.

Absence of peroxisomes in mouse hepatocytes causes mitochondrial and ER abnormalities

Ruud Dirkx, Ilse Vanhorebeek, Katrin Martens, Arno Schad, Markus Grabenbauer, Dariush Fahimi, Peter Declercq, Paul P. Van Veldhoven, Myriam Baes – 24 February 2005 – Peroxisome deficiency in men causes severe pathology in several organs, particularly in the brain and liver, but it is still unknown how metabolic abnormalities trigger these defects. In the present study, a mouse model with hepatocyte‐selective elimination of peroxisomes was generated by inbreeding Pex5‐loxP and albumin‐Cre mice to investigate the consequences of peroxisome deletion on the functioning of hepatocytes.

Metalloproteinase inhibitor TIMP‐1 affects hepatocyte cell cycle via HGF activation in murine liver regeneration

Fazilat F. Mohammed, Caroline J. Pennington, Zamaneh Kassiri, Jeffrey S. Rubin, Paul D. Soloway, Ulrich Ruther, Dylan R. Edwards, Rama Khokha – 22 February 2005 – Liver regeneration depends on timely restoration of cellular mass while orchestrating structural matrix remodeling. Matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) are known to regulate the extracellular matrix (ECM) turnover and, more recently, the processing of growth factors and cytokines.

Kupffer cells and macrophages are not required for hepatic hepcidin activation during iron overload

Giuliana Montosi, Elena Corradini, Cinzia Garuti, Samuele Barelli, Stefania Recalcati, Gaetano Cairo, Linda Valli, Elisa Pignatti, Chiara Vecchi, Francesca Ferrara, Antonello Pietrangelo – 22 February 2005 – Hepcidin, the iron hormone, is produced by the liver in response to iron and inflammation. Its synthesis during inflammation is triggered by cytokines, but the details of iron activation are obscure.

Contribution of Toll‐like receptor/myeloid differentiation factor 88 signaling to murine liver regeneration

Ekihiro Seki, Hiroko Tsutsui, Yuji Iimuro, Tetsuji Naka, Gakuhei Son, Shizuo Akira, Tadamitsu Kishimoto, Kenji Nakanishi, Jiro Fujimoto – 22 February 2005 – Toll‐like receptors (TLRs) act as innate immune signal sensors and play central roles in host defense. Myeloid differentiation factor (MyD) 88 is a common adaptor molecule required for signaling mediated by TLRs. When the receptors are activated, cells bearing TLRs produce various proinflammatory cytokines in a MyD88‐dependent manner.

The human liver clears both asymmetric and symmetric dimethylarginine

Michiel P.C. Siroen, Joost R. M. van der Sijp, Tom Teerlink, Cors van Schaik, Robert J. Nijveldt, Paul A. M. van Leeuwen – 22 February 2005 – Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) inhibit production of nitric oxide. The concentration of both dimethylarginines is regulated by urinary excretion, although ADMA, but not SDMA, is also subject to degradation by dimethylarginine dimethylaminohydrolase, which is highly expressed in the liver but also present in the kidney. The exact roles of the human liver and kidney in the metabolism of dimethylarginines are currently unknown.

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