Expression profiling of liver cell lines expressing entire or parts of hepatitis C virus open reading frame

Hideki Aizaki, Takashi Harada, Motoyuki Otsuka, Naohiko Seki, Mami Matsuda, Yue Wei Li, Hayato Kawakami, Yoshiharu Matsuura, Tatsuo Miyamura, Tetsuro Suzuki – 7 March 2007 – Although hepatitis C virus (HCV) is a causative agent of liver diseases, its mechanism of pathogenesis is still unclear, mainly because of the lack of adequate cell culture systems to support HCV infection and replication. In this report, we describe development and characterization of human hepatoma cell lines constitutively expressing entire (Hep394) or parts (Hep352, Hep3294) of the HCV open reading frame (ORF).

Dysregulation of glycogen synthase kinase‐3β signaling in hepatocellular carcinoma cells

Christèle Desbois‐Mouthon, Marie‐José Blivet‐Van Eggelpoë, Eléonore Beurel, Mathieu Boissan, Roland Delélo, Axelle Cadoret, Jacqueline Capeau – 7 March 2007 – It has been reported that upstream components of the insulin‐like growth factor (IGF) signaling axis could be overexpressed during hepatocarcinogenesis in humans and rodents. However, the signal transduction pathways activated downstream have been poorly studied.

Inhibition of HBV replication by siRNA in a stable HBV‐producing cell line

Masayoshi Konishi, Catherine H. Wu, George Y. Wu – 7 March 2007 – Potent inhibition of endogenous gene expression by RNA interference has been achieved by using sequence‐specific posttranscriptional gene silencing through the action of small interfering RNA molecules (siRNA). In these reports, the natural function of genes could be deduced through the ensuing loss of function. Based on the extraordinary effectiveness in silencing endogenous genes, we wondered whether siRNA could be applied against viral replication in a hepatitis B virus (HBV) model using HBV‐specific siRNA.

Feedback regulation of bile acid synthesis in primary human hepatocytes: Evidence that CDCA is the strongest inhibitor

Ewa Ellis, Magnus Axelson, Anna Abrahamsson, Gösta Eggertsen, Anders Thörne,, Grzegorz Nowak, Bo‐Göran Ericzon, Ingemar Björkhem,, Curt Einarsson – 7 March 2007 – Primary human hepatocytes were used to elucidate the effect of individual bile acids on bile acid formation in human liver. Hepatocytes were treated with free as well as glycine‐conjugated bile acids. Bile acid formation and messenger RNA (mRNA) levels of key enzymes and the nuclear receptor short heterodimer partner (SHP) were measured after 24 hours.

Influence of newly synthesized cholesterol on bile acid synthesis during chronic inhibition of bile acid absorption

Marco Bertolotti, Lisa Zambianchi, Lucia Carulli, Maria Sole Simonini, Marina Del Puppo, Marzia Galli Kienle, Paola Loria, Adriano Pinetti, Nicola Carulli – 7 March 2007 – The effects of newly synthesized cholesterol availability on bile acid synthesis are largely unknown, particularly in humans. The present study was aimed to study the changes induced on bile acid synthesis by simvastatin, a competitive inhibitor of hydroxymethyl glutaryl‐CoA (HMG‐CoA) reductase, the rate‐limiting enzyme of cholesterol synthesis, during pharmacologic interruption of the enterohepatic circulation.

High frequency of chimerism in transplanted livers

Irene Oi‐Lin Ng, Kok‐Lung Chan, Wai‐Hung Shek, Joyce Man‐Fong Lee, Daniel Yee‐Tak Fong, Chung‐Mau Lo, Sheung‐Tat Fan – 7 March 2007 – Recent studies have shown that primitive stem cells can mobilize and differentiate into hepatocytes. We investigated the time and extent in which cells of recipient origins could differentiate into hepatocytes and other cells in human liver allografts. Microsatellite analysis, which can assess quantitatively the proportions of recipient and donor DNA, was performed in posttransplantation liver biopsy specimens from 17 patients at various times.

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