Integration of genomic analysis and in vivo transfection to identify sprouty 2 as a candidate tumor suppressor in liver cancer

Susie A. Lee, Coral Ho, Ritu Roy, Cynthia Kosinski, Mohini A. Patil, Aaron D. Tward, Jane Fridlyand, Xin Chen – 19 December 2007 – Hepatocellular carcinoma (HCC) is 1 of the leading causes of cancer‐related deaths worldwide, yet the molecular genetics underlying this malignancy are still poorly understood. In our study, we applied statistical methods to correlate human HCC gene expression data obtained from complementary DNA (cDNA) microarrays and corresponding DNA copy number variation data obtained from array‐based comparative genomic hybridization.

Activation of liver X receptor sensitizes mice to gallbladder cholesterol crystallization

Hirdesh Uppal, Yonggong Zhai, Archana Gangopadhyay, Shaheen Khadem, Songrong Ren, James A. Moser, Wen Xie – 19 December 2007 – Gallstone disease is a hepatobiliary disorder due to biochemical imbalances in the gallbladder bile. In this report, we show that activation of nuclear receptor liver X receptor (LXR) sensitized mice to lithogenic diet–induced gallbladder cholesterol crystallization, which was associated with dysregulation of several hepatic transporters that efflux cholesterol, phospholipids, and bile salts.

Hemodynamic effects of urotensin II and its specific receptor antagonist palosuran in cirrhotic rats

Jonel Trebicka, Ludger Leifeld, Martin Hennenberg, Erwin Biecker, Andreas Eckhardt, Nicolas Fischer, Andrea Schulze Pröbsting, Christoph Clemens, Frank Lammert, Tilman Sauerbruch, Jörg Heller – 19 December 2007 – In cirrhosis, splanchnic vasodilation contributes to portal hypertension, subsequent renal sodium retention, and formation of ascites. Urotensin II(U‐II) is a constrictor of large conductive vessels. Conversely, it relaxes mesenteric vessels, decreases glomerular filtration, and increases renal sodium retention. In patients with cirrhosis, U‐II plasma levels are increased.

Acute liver failure: Summary of a workshop

William M. Lee, Robert H. Squires, Scott L. Nyberg, Edward Doo, Jay H. Hoofnagle – 19 December 2007 – Acute liver failure (ALF) is a rare but challenging clinical syndrome with multiple causes; a specific etiology cannot be identified in 15% of adult and 50% of pediatric cases. The course of ALF is variable and the mortality rate is high. Liver transplantation is the only therapy of proven benefit, but the rapidity of progression and the variable course of ALF limit its use.

Ciliary neurotrophic factor receptor α subunit–modulated multiple downstream signaling pathways in hepatic cancer cell lines and their biological implications

Xin Hu, Yingjun Zhao, Xianghuo He, Jinjun Li, Tao Wang, Weiping Zhou, Dafang Wan, Hongyang Wang, Jianren Gu – 19 December 2007 – Ciliary neurotrophic factor (CNTF) plays important roles in a variety of tissues including neural and non‐neural systems, but the function of CNTF and its receptor (CNTFR) in liver remains unclear. In this study, we demonstrate that CNTFRα is expressed heterogeneously in normal human liver and hepatocellular carcinoma (HCC) specimens but not in hepatoblastoma specimens.

A novel “patient‐like” model of cholangiocarcinoma progression based on bile duct inoculation of tumorigenic rat cholangiocyte cell lines

Alphonse E. Sirica, Zichen Zhang, Guan‐Hua Lai, Toru Asano, Xue‐Ning Shen, Deanna J. Ward, Arvind Mahatme, Jennifer L. DeWitt – 14 December 2007 – Intrahepatic cholangiocarcinoma typically presents in an advanced stage in which treatment options are limited. In an effort to recapitulate key biological and clinical features of the progressive disease, we established a novel rat model based on bile duct inoculation of rat cholangiocyte cell lines in different stages of tumor progression.

Increased oxidative stress in cirrhotic rat livers: A potential mechanism contributing to reduced nitric oxide bioavailability

Jorge Gracia‐Sancho, Bàrbara Laviña, Aina Rodríguez‐Vilarrupla, Héctor García‐Calderó, Mercedes Fernández, Jaume Bosch, Joan‐Carles García‐Pagán – 10 December 2007 – In cirrhotic livers, decreased nitric oxide (NO) bioavailability is a major factor increasing intrahepatic vascular tone. In several vascular disorders, an increase in superoxide (O2−) has been shown to contribute to reduced NO bioavailability through its reaction with NO to form peroxynitrite. This study was aimed to test the hypothesis that, in cirrhotic livers, increased O2−, by reacting with NO, reduces NO bioavailability.

Distinct hepatitis C virus core and F protein quasispecies in tumoral and nontumoral hepatocytes isolated via microdissection

Rodolphe Sobesky, Cyrille Feray, François Rimlinger, Nicolas Derian, Alexandre Dos Santos, Anne‐Marie Roque‐Afonso, Didier Samuel, Christian Bréchot, Valérie Thiers – 28 November 2007 – Hepatitis C virus (HCV) genetic variability may be involved in liver carcinogenesis. We investigated HCV core and corresponding putative F protein genetic variability in hepatocellular carcinoma (HCC) and cirrhotic nodules. Hepatocyte clusters from 7 patients with HCC and HCV1b‐related cirrhosis were isolated via microdissection of HCC tissues and 2 nontumoral cirrhotic nodules.

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