Topoisomerase inhibitor camptothecin sensitizes mouse hepatocytes in vitro and in vivo to TNF‐mediated apoptosis

Hannes Hentze, Markus Latta, Gerald Künstle, Saravanakumar Dhakshinamoorthy, Poh Yong Ng, Alan G. Porter, Albrecht Wendel – 26 April 2004 – Topoisomerases are nuclear enzymes that maintain and modulate DNA structure. Inhibitors of topoisomerases like camptothecin (CPT), etoposide, and others are widely used antitumor drugs that interfere with transcription, induce DNA strand breaks, and trigger apoptosis preferentially in dividing cells.

An oncolytic adenoviral vector of Smac increases antitumor activity of TRAIL against HCC in human cells and in mice

Zifei Pei, Liang Chu, Weiguo Zou, Zilai Zhang, Songbo Qiu, Rong Qi, Jinfa Gu, Cheng Qian, Xinyuan Liu – 26 April 2004 – Hepatocellular carcinoma (HCC) displays a high resistance to tumor necrosis factor–related apoptosis–inducing ligand (TRAIL)–mediated cell death. To increase sensitivity of HCC cells to TRAIL, we have constructed an oncolytic adenoviral vector (ZD55) and used this vector to deliver second mitochondria‐derived activator of caspases (Smac) and TRAIL genes (ZD55‐Smac and ZD55‐TRAIL, respectively) into HCC cells.

A double‐blind randomized controlled trial of infliximab associated with prednisolone in acute alcoholic hepatitis

Sylvie Naveau, Sylvie Chollet‐Martin, Sébastien Dharancy, Philippe Mathurin, Pauline Jouet, Marie‐Astrid Piquet, Thierry Davion, Frédéric Oberti, Philippe Broët, Dominique Emilie, for the Foie‐Alcool group of the Association Française pour l'Etude du Foie (AFEF) – 26 April 2004 – Tumor necrosis factor‐α (TNF‐α) may contribute to the progression of acute alcoholic hepatitis (AAH). The aim of this study was to evaluate the efficacy of an association of infliximab and prednisolone at reducing the 2‐month mortality rate among patients with severe AAH.

Murine alanine aminotransferase: cDNA cloning, functional expression, and differential gene regulation in mouse fatty liver

Sanjay B. Jadaho, Rong‐Ze Yang, Qiang Lin, Hong Hu, Frank A. Anania, Alan R. Shuldiner, Da‐Wei Gong – 26 April 2004 – Alanine aminotransferase (ALT) is a widely used index of liver integrity or hepatocellular damage in clinics as well as a key enzyme in intermediatary metabolism. In this study, we have cloned the complementary DNAs of murine homologues of human alanine aminotransferase 1 and 2 (ALT1 and ALT2). The deduced peptides of murine ALT1 (mALT1) and ALT2 (mALT2) share 87% and 93% identity, respectively, with their human counterparts at the amino acid level.

Caspase induction by IgA antimitochondrial antibody: IgA‐mediated biliary injury in primary biliary cirrhosis

Shuji Matsumura, Judy Van de Water, Patrick Leung, Joseph A. Odin, Kazuhide Yamamoto, Gregory J. Gores, Keith Mostov, Aftab A. Ansari, Ross L. Coppel, Yasushi Shiratori, M. Eric Gershwin – 26 April 2004 – Anti‐mitochondrial antibodies (AMAs) have long been recognized as a serological hallmark of primary biliary cirrhosis (PBC). Although high titers of immunoglobulin (Ig)A AMAs are found in bile, saliva, and urine of patients, a pathogenic role for this antibody has remained elusive.

Pivotal role of superoxide anion and beneficial effect of antioxidant molecules in murine steatohepatitis

Alexis Laurent, Carole Nicco, Jeanne Tran Van Nhieu, Didier Borderie, Christiane Chéreau, Filomena Conti, Patrick Jaffray, Olivier Soubrane, Yvon Calmus, Bernard Weill, Frédéric Batteux – 26 April 2004 – Nonalcoholic fatty liver disease, frequently associated with obesity, can lead to nonalcoholic steatohepatitis (NASH) and cirrhosis. The pathophysiology of NASH is poorly understood, and no effective treatment is available. In view of a potential deleterious role for reactive oxygen species (ROS), we investigated the origin of ROS overproduction in NASH.

Synbiotic modulation of gut flora: Effect on minimal hepatic encephalopathy in patients with cirrhosis

Qing Liu, Zhong Ping Duan, Da Kang Ha, Stig Bengmark, Jelica Kurtovic, Stephen M. Riordan – 26 April 2004 – Minimal hepatic encephalopathy (MHE) is an important disorder that may seriously impair daily functioning and quality of life in patients with cirrhosis. Treatment with lactulose is of benefit. The possible role of synbiotics (probiotics and fermentable fiber) has not been assessed. We screened 97 consecutive cirrhotic patients without overt hepatic encephalopathy for MHE using the number connection test and measurement of brainstem auditory evoked potentials.

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