Germ‐line mutations of the p16INK4(MTS1) gene occur in a subset of patients with hepatocellular carcinoma

P Chaubert, R Gayer, A Zimmermann, C Fontolliet, B Stamm, F Bosman, P Shaw – 30 December 2003 – The molecular mechanisms of hepatocarcinogenesis are poorly understood. Only very recently has there been a suggestion of familial hepatocellular carcinoma (HCC). We have analyzed the status of the p16INK4(MTS1) gene, a cyclin‐dependent kinase inhibitor, in 26 patients with HCC of different etiologies. Four patients carried hemizygous germ‐line point mutations of the p16INK4(MTS1) gene, suggesting the existence of familial HCC involving this gene.

Effect of cell density and epidermal growth factor on the inducible expression of CYP3A and CYP1A genes in human hepatocytes in primary culture

J Greuet, L Pichard, J C Ourlin, C Bonfils, J Domergue, P Le Treut, P Maurel – 30 December 2003 – The influence of cell density and epidermal growth factor (EGF) on the expression and inducibility of cytochrome P450 (CYP) genes of the CYP3A and CYP1A families in adult human hepatocytes in primary culture has been evaluated. Only when cultured at subconfluence and in the presence of EGF did hepatocytes exhibit a proliferative response, assessed by measuring DNA synthesis and cyclin A accumulation.

Expression of costimulatory molecules B7‐1 (CD80) and B7‐2 (CD86) on human hepatocellular carcinoma

T Tatsumi, T Takehara, K Katayama, K Mochizuki, M Yamamoto, T Kanto, Y Sasaki, A Kasahara, N Hayashi – 30 December 2003 – Costimulation mediated by costimulatory molecules, such as B7‐1 and B7‐2, which are ligands for the CD28/cytolytic T lymphocyte associated antigen (CTLA)‐4 counter‐receptor, plays an important role in the induction of T cell‐mediated antitumor immunity.

Pretreatment virus load and multiple amino acid substitutions in the interferon sensitivity–determining region predict the outcome of interferon treatment in patients with chronic genotype 1b hepatitis C virus infection

K Chayama, A Tsubota, M Kobayashi, K Okamoto, M Hashimoto, Y Miyano, H Koike, M Kobayashi, I Koida, Y Arase, S Saitoh, Y Suzuki, N Murashima, K Ikeda, H Kumada – 30 December 2003 – Hepatitis C virus (HCV) genotype 1b and high pretreatment virus load are predictive factors of poor response to interferon therapy in patients with chronic hepatitis C. To further examine the factors predicting the response to interferon in patients with genotype 1b infection, we analyzed 110 consecutive patients with HCV who were treated with a total of 624 million units of lymphoblastoid interferon alfa.

Effects of extended cold preservation and transplantation on the rat liver microcirculation

H Imamura, A Brault, P M Huet – 30 December 2003 – Liver sinusoidal endothelial cell impairment and/or microcirculatory disturbances are thought to induce storage‐related graft failure; however, the respective roles of changes induced by extended cold preservation and transplantation, as well as their interactions, are still unknown.

Expression of hepatocyte growth factor and its receptor, the c‐met proto‐oncogene, in hepatocellular carcinoma

T Ueki, J Fujimoto, T Suzuki, H Yamamoto, E Okamoto – 30 December 2003 – The c‐met proto‐oncogene encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF), a potent mitogen and motogen for epithelial cells. Because of its profound effects on cell growth and motility, HGF may be important in the development of cancer metastases in hepatocellular carcinoma (HCC).

Liver cell proliferation induced by nafenopin and cyproterone acetate is not associated with increases in activation of transcription factors NF‐κB and AP‐1 or with expression of tumor necrosis factor α

M Menegazzi, A Carcereri‐De Prati, H Suzuki, H Shinozuka, M Pibiri, R Piga, A Columbano, G M Ledda‐Columbano – 30 December 2003 – Our previous studies have shown a different pattern of immediate early gene and growth factor gene expression between compensatory liver regeneration occurring after cell loss/death and direct hyperplasia induced by primary mitogens.

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