Association of gankyrin protein expression with early clinical stages and insulin‐like growth factor‐binding protein 5 expression in human hepatocellular carcinoma

Atsushi Umemura, Yoshito Itoh, Katsuhiko Itoh, Kanji Yamaguchi, Tomoki Nakajima, Hiroaki Higashitsuji, Hitoshi Onoue, Manabu Fukumoto, Takeshi Okanoue, Jun Fujita – 26 January 2008 – Gankyrin (also known as PSMD10) is a liver oncoprotein that interacts with multiple proteins including MDM2 and accelerates degradation of the tumor suppressors p53 and Rb. We produced a monoclonal anti‐gankyrin antibody and immunohistochemically assessed the clinicopathological significance of gankyrin overexpression in 43 specimens of human hepatocellular carcinoma (HCC).

Interacting alleles of the coinhibitory immunoreceptor genes cytotoxic T‐lymphocyte antigen 4 and programmed cell‐death 1 influence risk and features of primary biliary cirrhosis

Brian D. Juran, Elizabeth J. Atkinson, Erik M. Schlicht, Brooke L. Fridley, Gloria M. Petersen, Konstantinos N. Lazaridis – 26 January 2008 – Autoimmune diseases such as primary biliary cirrhosis (PBC) result from failure in the immune mechanisms that establish and maintain self‐tolerance. Evidence suggests that these processes are shared among the spectrum of autoimmune syndromes and are likely genetically determined.

Transient elastography is unreliable for detection of cirrhosis in patients with acute liver damage

Abdurrahman Sagir, Andreas Erhardt, Marcus Schmitt, Dieter Häussinger – 26 January 2008 – Transient elastography [FibroScan (FS)] is a rapid, noninvasive, and reproducible method for measuring liver stiffness, which correlates with the degree of liver fibrosis in patients with chronic hepatitis. Whether FS is useful in the detection of preexisting liver fibrosis/cirrhosis in patients presenting with acute liver damage is unclear. Patients with acute liver damage of different etiologies were analyzed.

Telbivudine versus lamivudine in Chinese patients with chronic hepatitis B: Results at 1 year of a randomized, double‐blind trial

Jinlin Hou, You‐Kuan Yin, Daozhen Xu, Deming Tan, Junqi Niu, Xiaqiu Zhou, Yuming Wang, Limin Zhu, Yongwen He, Hong Ren, Mobin Wan, Chengwei Chen, Shanming Wu, Yagang Chen, Jiazhang Xu, Qinhuan Wang, Lai Wei, George Chao, Barbara Fielman Constance, George Harb, Nathaniel A. Brown, Jidong Jia – 26 January 2008 – Chronic hepatitis B and its life‐threatening sequelae are highly prevalent in China. There is a need for effective new therapies to suppress hepatitis B virus (HBV) replication and ameliorate liver disease.

Activation of peroxisome proliferator‐activated receptor‐α inhibits the injurious effects of adiponectin in rat steatotic liver undergoing ischemia–reperfusion

Marta Massip‐Salcedo, M. Amine Zaouali, Susagna Padrissa‐Altés, Arani Casillas‐Ramirez, Joan Rodés, Joan Roselló‐Catafau, Carmen Peralta – 26 January 2008 – Hepatic steatosis is a major risk factor in ischemia–reperfusion (I/R). Adiponectin acts as an antiobesity and anti‐inflammatory hormone. Adiponectin activates peroxisome proliferator‐activated receptor‐α (PPAR‐α), a transcription factor that regulates inflammation in liver disease.

The methionine connection: Homocysteine and hydrogen sulfide exert opposite effects on hepatic microcirculation in rats

Eleonora Distrutti, Andrea Mencarelli, Luca Santucci, Barbara Renga, Stefano Orlandi, Annibale Donini, Vijay Shah, Stefano Fiorucci – 26 January 2008 – Increased intrahepatic resistance in cirrhotic livers is caused by endothelial dysfunction and impaired formation of two gaseous vasodilators, nitric oxide (NO) and hydrogen sulfide (H2S). Homocysteine, a sulfur‐containing amino acid and H2S precursor, is formed from hepatic methionine metabolism. In the systemic circulation, hyperhomocystenemia impairs vasodilation and NO production from endothelial cells.

Leptin's mitogenic effect in human liver cancer cells requires induction of both methionine adenosyltransferase 2A and 2β

Komal Ramani, Heping Yang, Meng Xia, Ainhoa Iglesias Ara, José M. Mato, Shelly C. Lu – 26 January 2008 – Leptin is an adiopokine that plays a pivotal role in the progression of liver fibrogenesis and carcinogenesis. Recently, leptin was shown to be mitogenic in human liver cancer cell lines HepG2 and Huh7. Whether leptin can act as a mitogen in normal hepatocytes is unclear. Methionine adenosyltransferase (MAT) is an essential enzyme that catalyzes the formation of S‐adenosylmethionine (SAMe), the principal methyl donor and precursor of polyamines.

Isolation and characterization of a novel oncogene, amplified in liver cancer 1, within a commonly amplified region at 1q21 in hepatocellular carcinoma

Ning‐Fang Ma, Liang Hu, Jackie M. Fung, Dan Xie, Bo‐Jian Zheng, Leilei Chen, Dong‐Jiang Tang, Li Fu, Zhenguo Wu, Muhan Chen, Yan Fang, Xin‐Yuan Guan – 26 January 2008 – Amplification of 1q21 is the most frequent genetic alteration in human hepatocellular carcinoma (HCC), being detected in 58%‐78% of primary HCC cases by comparative genomic hybridization. Recently, we isolated a candidate oncogene, Amplified in Liver Cancer 1 (ALC1), from 1q21 by hybrid selection. Here we demonstrate that ALC1 was frequently amplified and overexpressed in HCC.

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