Altered expression of mitogen‐activated protein kinases in a rat model of experimental hepatocellular carcinoma

I H McKillop, C M Schmidt, P A Cahill, J V Sitzmann – 30 December 2003 – The mitogen‐activated protein kinase (MAPK) cascade acts as a focal point for signal transduction following activation of both G‐protein‐linked and tyrosine kinase growth factor receptors. A common intermediate between both of these diverse receptor subtypes includes the small guanosine triphosphate (GTP)‐binding protein, p21ras.

Bile acid–independent bile flow is differently regulated by glucagon and secretin in humans after orthotopic liver transplantation

R Lenzen, J Elster, C Behrend, K Hampel, W Bechstein, P Neuhaus – 30 December 2003 – The present study characterizes recovery of bile secretion after orthotopic liver transplantation (OLT) in humans with special regard to hormonal regulation of bile acid‐independent bile flow by glucagon and secretin. Sixty‐seven patients with an uncomplicated postoperative course were studied during the first 3 weeks after OLT to determine normalization of bile flow.

Effect of a xanthine analog on human hepatocellular carcinoma cells (Alexander) in culture and in xenografts in SCID mice

L Marucci, L Varticovski, I M Arias – 30 December 2003 – Hepatocellular carcinoma (HCC) frequently overexpresses the MDR1 gene and is resistant to drugs transported by the multidrug‐resistance efflux pump. A xanthine analog, 1‐(11‐dodecylamino‐10‐hydroxyundecyl)‐ 3,7‐dimethylxanthine (CT‐2584,CTI), is cytotoxic to many tumors in culture and was four times more effective than verapamil in inhibiting Rhodamine 123 secretion in MDR1‐overexpressing Chinese hamster ovary cells.

Hepatocellular carcinoma in primary biliary cirrhosis and its impact on outcomes

D E Jones, J V Metcalf, J D Collier, M F Bassendine, O F James – 30 December 2003 – In this study we have determined the incidence of hepatocellular carcinoma (HCC) development in primary biliary cirrhosis (PBC) and its effects on patient survival. Six hundred and sixty seven patients with liver histology compatible with or diagnostic of PBC were seen over a 20‐year period.

Spontaneous and iatrogenic spreading of liver‐derived cells into peripheral blood of patients with primary liver cancer

M Louha, K Poussin, N Ganne, H Zylberberg, B Nalpas, J Nicolet, F Capron, O Soubrane, C Vons, S Pol, M Beaugrand, P Berthelot, D Franco, J C Trinchet, C Brechot, P Paterlini – 30 December 2003 – The prognosis for patients with primary liver cancer (PLC) often depends on tumor recurrence and the development of extrahepatic metastases, particularly after liver transplantation. We have developed a sensitive test to detect both spontaneous circulation of tumor cells and the spread of liver cells due to chemoembolization and alcoholization.

Transient immunosuppression with FK506 permits long‐term expression of therapeutic genes introduced into the liver using recombinant adenoviruses in the rat

Y Ilan, V K Jona, K Sengupta, A Davidson, M S Horwitz, N Roy‐Chowdhury, J Roy‐Chowdhury – 30 December 2003 – The host immune response limits the duration of expression of adenovirally transduced genes and precludes long‐term gene expression upon re‐administration of the virus. In this study we wished to evaluate whether short‐term immunosuppression of the host, at the time of recombinant virus administration, would allow expression of the therapeutic gene product upon virus reinjection. Gunn rats were used as recipients of recombinant adenoviruses expressing human BUGT (Ad‐hBUGT) or E.

Critical role of Fas/Fas ligand interaction in CD28‐independent pathway of allogeneic murine hepatocyte rejection

T Kawahara, S Kasai, H Yagita, M Sawa, K Kato, M Azuma, A Nakajima, K Okumura, S Futagawa, M Mito – 30 December 2003 – Cytolytic induction of T cells requires both the T‐cell receptor (TCR)‐mediated antigenic stimulation and the CD28‐mediated co‐stimulatory signal. Blockade of the interactions between CD28 and its ligands, CD80 and CD86, prolongs the survival of allografts in some transplantation models.

Relationship between biochemical, virological, and histological response during interferon treatment of chronic hepatitis C

M L Shiffman, C M Hofmann, E B Thompson, A Ferreira‐Gonzalez, M J Contos, A Koshy, V A Luketic, A J Sanyal, A S Mills, C T Garrett – 30 December 2003 – The present study was conducted to evaluate the relationship between biochemical, virological, and histological response during the course of interferon therapy. Ninety consecutive patients with well‐documented chronic hepatitis C virus (HCV) were treated with 5 MU of interferon alfa‐2b three times weekly for 6 months. Liver biopsy was performed, and serum HCV RNA titer was measured before and at the completion of interferon treatment.

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