Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection

Yasuhiro Asahina, Kaoru Tsuchiya, Nobuharu Tamaki, Itsuko Hirayama, Tomohiro Tanaka, Mitsuaki Sato, Yutaka Yasui, Takanori Hosokawa, Ken Ueda, Teiji Kuzuya, Hiroyuki Nakanishi, Jun Itakura, Yuka Takahashi, Masayuki Kurosaki, Nobuyuki Enomoto, Namiki Izumi – 23 July 2010 – An increase in the aging population is an impending problem. A large cohort study was carried out to determine the influence of aging and other factors on hepatocarcinogenesis in patients treated with interferon. Biopsy‐proven 2547 chronic hepatitis C patients registered at our referral center since 1992 were included.

Cytosolic calcium regulates liver regeneration in the rat

Laura Lagoudakis, Isabelle Garcin, Boris Julien, Kis Nahum, Dawidson A. Gomes, Laurent Combettes, Michael H. Nathanson, Thierry Tordjmann – 23 July 2010 – Liver regeneration is regulated by growth factors, cytokines, and other endocrine and metabolic factors. Calcium is important for cell division, but its role in liver regeneration is not known. The purpose of this study was to understand the effects of cytosolic calcium signals in liver growth after partial hepatectomy (PH).

Octamer 4 (Oct4) mediates chemotherapeutic drug resistance in liver cancer cells through a potential Oct4–AKT–ATP‐binding cassette G2 pathway

Xiao Qi Wang, Weg M. Ongkeko, Lin Chen, Zhen Fan Yang, Ping Lu, Kwok Kin Chen, Jay P. Lopez, Ronnie T.P. Poon, Sheung Tat Fan – 23 July 2010 – Chemoresistance presents a major obstacle to the efficacy of chemotherapeutic treatment of cancers. Using chemotherapeutic drugs to select drug‐resistant cancer cells in hepatocellular carcinoma (HCC) and several other cancer cell lines, we demonstrate that chemoresistant cells displayed cancer stem cell features, such as increased self‐renewal ability, cell motility, multiple drug resistance, and tumorigenicity.

Glycosylation of fibroblast growth factor receptor 4 is a key regulator of fibroblast growth factor 19–mediated down‐regulation of cytochrome P450 7A1

Vassilis Triantis, Eirikur Saeland, Nora Bijl, Ronald P. Oude‐Elferink, Peter L. M. Jansen – 23 July 2010 – De novo bile acid synthesis in the liver needs to be tightly regulated in order to maintain optimal bile flow and prevent cholestasis. In the liver, fibroblast growth factor 19 (FGF19) regulates bile acid synthesis by down‐regulating messenger RNA levels of cytochrome P450 7A1 (CYP7A1). FGF19 acts through fibroblast growth factor receptor 4 (FGFR4), and β‐Klotho has recently been recognized as a modulator of FGFR4 activity.

Cytosolic phospholipase A2α and peroxisome proliferator‐activated receptor γ signaling pathway counteracts transforming growth factor β–mediated inhibition of primary and transformed hepatocyte growth

Chang Han, William C. Bowen, Guiying Li, Anthony J. Demetris, George K. Michalopoulos, Tong Wu – 23 July 2010 – Hepatocellular carcinoma often develops in the setting of abnormal hepatocyte growth associated with chronic hepatitis and liver cirrhosis. Transforming growth factor β (TGF‐β) is a multifunctional cytokine pivotal in the regulation of hepatic cell growth, differentiation, migration, extracellular matrix production, stem cell homeostasis, and hepatocarcinogenesis. However, the mechanisms by which TGF‐β influences hepatic cell functions remain incompletely defined.

c‐Jun mediates hepatitis C virus hepatocarcinogenesis through signal transducer and activator of transcription 3 and nitric oxide–dependent impairment of oxidative DNA repair

Keigo Machida, Hidekazu Tsukamoto, Jian‐Chang Liu, Yuan‐Ping Han, Sugantha Govindarajan, Michael M. C. Lai, Shizuo Akira, Jing‐hsiung James Ou – 23 July 2010 – Hepatocellular carcinoma (HCC) occurs in a significant number of patients with hepatitis C virus (HCV) infection. HCV causes double‐strand DNA breaks and enhances the mutation frequency of proto‐oncogenes and tumor suppressors. However, the underlying mechanisms for these oncogenic events are still elusive.

Lipid rafts are essential for peroxisome biogenesis in HepG2 cells

Jannes Woudenberg, Krzysztof P. Rembacz, Mark Hoekstra, Antonella Pellicoro, Fiona A. J. van den Heuvel, Janette Heegsma, Sven C. D. van IJzendoorn, Andreas Holzinger, Tsuneo Imanaka, Han Moshage, Klaas Nico Faber – 23 July 2010 – Peroxisomes are particularly abundant in the liver and are involved in bile salt synthesis and fatty acid metabolism.

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