Immunohistologic study on the expressions of α‐fetoprotein and protein induced by vitamin K absence or antagonist II in surgically resected small hepatocellular carcinoma

Miwako Fujioka, Yutaka Nakashima, Osamu Nakashima, Masamichi Kojiro – 30 December 2003 – Sixty‐eight cases of single hepatocellular carcinoma (HCC) with less than 3 cm of diameter were immunohistochemically examined for the expressions of α‐fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA‐II). In cancerous tissues, the expression rate was significantly higher for PIVKA‐II (34 cases [50%]) than AFP (21 cases [31%]) (P < .05), suggesting a higher specificity of PIVKA‐II to small HCC.

Effective treatment of small murine hepatocellular carcinoma by dendritic cells

Wei‐Chen Lee, Hui‐Chuan Wang, Long‐Bin Jeng, Yang‐Jen Chiang, Chen‐Rong Lia, Pei‐Fang Huang, Miin‐Fu Chen, Shiguang Qian, Lina Lu – 30 December 2003 – Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis. This investigation examined whether dendritic cell–based immunotherapy can treat murine HCC effectively. Bone marrow–derived dendritic cells were propagated from C57BL/10J mice in GM‐CSF (4 ng/mL) and interleukin (IL)‐4 (1,000 μ/mL). The dendritic cells were pulsed with a Hepa1‐6 lysate overnight and employed to treat murine HCC.

High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: A potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis

Valerie Paradis, Gabriel Perlemuter, Franck Bonvoust, Delphine Dargere, Beatrice Parfait, Michel Vidaud, Marc Conti, Stephane Huet, Nathalie Ba, Catherine Buffet, Pierre Bedossa – 30 December 2003 – Nonalcoholic steatohepatitis (NASH) may progress to liver fibrosis and cirrhosis. Mechanisms directly involved in the development of fibrosis have been poorly investigated.

Oxidized low‐density lipoproteins bind to the scavenger receptor, CD36, of hepatic stellate cells and stimulate extracellular matrix synthesis

Wilhelm Schneiderhan, Alexandra Schmid‐Kotsas, Jinshun Zhao, Adolf Grünert, Andreas Nüssler, Hans Weidenbach, Andre Menke, Roland M. Schmid, Guido Adler, Max G. Bachem – 30 December 2003 – Cumulating evidence suggests that oxidative stress resulting in lipid peroxidation and protein modification is involved in the pathogenesis of chronic liver injury and fibrogenesis. We investigated the effects of oxidized low‐density lipoproteins (oxLDL) on collagen and fibronectin synthesis of cultured human and rat hepatic stellate cells (HSC).

Chronic ethanol consumption stimulates hepatitis B virus gene expression and replication in transgenic mice

Jonathan Larkin, Marcia M. Clayton, Jie Liu, Mark A. Feitelson – 30 December 2003 – Epidemiologic observations show a higher frequency of hepatitis B virus (HBV) serologic markers in chronic alcoholics compared with the general population. This may be the result of an increased susceptibility of alcoholics to infection and/or to an ethanol‐mediated stimulation of HBV gene expression and replication. To test the latter hypothesis, HBV transgenic SCID mice, which support consistent levels of virus replication, were fed with a standard Lieber‐DiCarli or isocaloric diet for 5 weeks.

Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy

Man‐Fung Yuen, Erwin Sablon, Chee‐Kin Hui, He‐Jun Yuan, Hilde Decraemer, Ching‐Lung Lai – 30 December 2003 – Factors associated with hepatitis B virus (HBV) DNA breakthrough and the significance of YMDD variants without the presence of wild‐type YMDD during prolonged lamivudine treatment are unknown. We studied the amino acid sequence of codon 552 (YMDD motif) and codon 528 by means of a line probe assay in 159 chronic HBV patients (median follow‐up 29.6 months).

Increased production of vascular endothelial growth factor in peritoneal macrophages of cirrhotic patients with spontaneous bacterial peritonitis

Pilar Cejudo‐Martín, Josefa Ros, Miguel Navasa, Javier Fernández, Guillermo Fernádez‐Varo, Luis Ruiz‐del‐Arbol, Francisca Rivera, Vicente Arroyo, Juan Rodés, Wladimiro Jiménez – 30 December 2003 – Spontaneous bacterial peritonitis (SBP) is a common complication of cirrhotic patients with ascites that usually results in renal failure and death despite the efficacy of the current antibiotic therapy. The pathogenesis of these phenomena is poorly known but it has been related to the production of vasoactive cell mediators locally acting on the splanchnic vasculature.

High rates of hepatocellular carcinoma in cirrhotic patients with high liver cell proliferative activity

Maria Francesca Donato, Eliana Arosio, Ersilio Del Ninno, Guido Ronchi, Pietro Lampertico, Alberto Morabito, Maria Rita Balestrieri, Massimo Colombo – 30 December 2003 – The prevalence, risk factors, and clinical significance of high liver cell proliferative activity were investigated in 208 well‐compensated cirrhotic patients (150 men; 50 years; 135 with chronic hepatitis C) who had been under prospective surveillance for hepatocellular carcinoma (HCC) with annual abdominal ultrasound (US) and serum α‐fetoprotein (AFP) determination.

Hepatitis B virus X protein increases expression of p21Cip‐1/WAF1/MDA6 and p27Kip‐1 in primary mouse hepatocytes, leading to reduced cell cycle progression

Liang Qiao, Kevin Leach, Robert McKinstry, Donna Gilfor, Adly Yacoub, Jong Sung Park, Steven Grant, Philip B. Hylemon, Paul B. Fisher, Paul Dent – 30 December 2003 – Previously, we have linked prolonged intense mitogen‐activated protein kinase (MAP kinase; MAPK) signaling in hepatocytes to increased expression of p21Cip‐1/WAF1/MDA6 (p21) and p16INK4a (p16), that leads to a p21‐dependent growth arrest. In this study, we investigated the impact of hepatitis B virus X protein (pX) expression on MAPK‐modulated cell cycle progression in primary mouse hepatocytes.

Bile acid feeding increased proliferative activity and apical bile acid transporter expression in both small and large rat cholangiocytes

Gianfranco Alpini, Yoshiyuki Ueno, Shannon S. Glaser, Marco Marzioni, Jo Lynne Phinizy, Heather Francis, Gene LeSage – 30 December 2003 – Bile acids (BA) enter cholangiocytes by the Na+‐dependent apical BA transporter (ABAT). By this mechanism, taurocholate (TC) and taurolithocholate (TLC) increase cholangiocyte proliferation. No in vivo studies exist regarding the anatomical sites involved in BA‐regulation of cholangiocyte growth. Specific cholangiocyte subpopulations participate in BA‐regulated proliferation.

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