Advancing the diagnosis and treatment of hepatocellular carcinoma

J. Wallis Marsh, Sydney D. Finkelstein, Myron E. Schwartz, M. Isabel Fiel, Igor Dvorchik – 21 March 2005 – We analyzed global gene expression patterns of 91 human hepatocellular carcinomas (HCCs) to define the molecular characteristics of the tumors and to test the prognostic value of the expression profiles. Unsupervised classification methods revealed two distinctive subclasses of HCC that are highly associated with patient survival. This association was validated via 5 independent supervised learning methods.

Prediction of fibrosis in HCV‐infected liver transplant recipients with a simple noninvasive index

Salvador Benlloch, Marina Berenguer, Martín Prieto, José Miguel Rayón, Victoria Aguilera, Joaquín Berenguer – 21 March 2005 – Recurrent hepatitis C is a frequent event in liver transplantation (LT). Serial liver biopsies remain the best way of monitoring disease progression. Due to the limitations of a liver biopsy, there is an interest in developing noninvasive markers of liver fibrosis. While several models for predicting fibrosis have been constructed in patients who have not undergone transplantation, these are lacking in the transplant population.

Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: A three‐year randomized trial

Henna Rautiainen, Päivi Kärkkäinen, A‐L Karvonen, Heimo Nurmi, Pekka Pikkarainen, Hannu Nuutinen, Martti Färkkilä – 7 March 2005 – Ursodeoxycholic acid (UDCA) is a safe medical therapy for primary biliary cirrhosis (PBC), but its effect on liver histology remains uncertain. Budesonide is a glucocorticoid with high receptor activity and high first‐pass metabolism in liver. We evaluated the combination of budesonide and UDCA on liver histology and compared this with UDCA alone in a 3‐year prospective, randomized, open multicenter study.

Direct hepatic fate specification from mouse embryonic stem cells

Takumi Teratani, Hanako Yamamoto, Kazuhiko Aoyagi, Hiroki Sasaki, Akira Asari, Gary Quinn, Hideo Sasaki, Masaaki Terada, Takahiro Ochiya – 1 March 2005 – The molecules responsible for hepatic differentiation from embryonic stem (ES) cells have yet to be elucidated. Here we have identified growth factors that allow direct hepatic fate‐specification from ES cells by using simple adherent monolayer culture conditions.

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.

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.

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.

SELDI‐TOF MS profiling of serum for detection of the progression of chronic hepatitis C to hepatocellular carcinoma

E. Ellen Schwegler, Lisa Cazares, Laura F. Steel, Bao‐Ling Adam, David A. Johnson, O. John Semmes, Timothy M. Block, Jorge A. Marrero, Richard R. Drake – 22 February 2005 – Proteomic profiling of serum is an emerging technique to identify new biomarkers indicative of disease severity and progression. The objective of our study was to assess the use of surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometry (SELDI‐TOF MS) to identify multiple serum protein biomarkers for detection of liver disease progression to hepatocellular carcinoma (HCC).

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