B型肝炎pre-S突變蛋白誘發肝炎的分子機制研究(B)HepatitisBvirus(.docVIP

病毒相關腫瘤之致病機制與標靶治療Pathogenesis and Therapy of Virus-associated Cancers) 蘇益仁 Ih-Jen Su 特聘研究員Distinguish InvestigatorPhone: (06) 2083422 ext. 65201 Fax: (06) 2083466E-mail: suihjen@nhri.org.tw Dr. Ih-Jen Su obtained his MD from College of Medicine, National Taiwan University in 1969 and Ph.D from Institute of Pathology, National Taiwan University in 1988. He became a professor in Department of Pathology, National Taiwan University in 1991. He is the recipient of many awards and honors in recognition of his contribution to Pathology research. He joined the Division of Infectious Diseases (formerly Division of Clinical Research), NHRI as a director in 2002. Research Interests ＊Biology and pathology of malignant lymphoma, particularly EBV-associated T cell lymphoma. ＊Pathogenesis and mechanism of HBV pre-S mutants and hepatocarcinogenesis. ＊Pathogenesis and therapy of virus-associated hemophagocytic syndrome  HBV has been closely associated with the development of HCC. In the past years, we identified per-S mutants prevalent in patients with HCC for up to 65%, as compared to the below 10% in patients with chronic hepatitis. The emergence of pre-S mutant in serum may provide a potentially predictive marker for the development of HCC. The pre-S mutants are retained in endoplasmic reticulum (ER) and induces ER stress (Am J Pathol, 2004). The pre-S2 mutant can upregulate cyclin A and induces nodular transformation of hepatocytes and hepatoma in transgenic mice. (Hepatology, 2005；Cancer science, 2006；J Gastroenterol Hepatol, 2008). In the past year, we found endothelial growth factor (VEGF)-A was upregulated by pre-S mutants. The enhanced expression of VEGF-A and activation of Akt/mTOR in GGHs provides a potential mechanism to explain the progression from GGHs to HCC in chronic HBV infection (Hepatology, 2009 in press). In the coming years, pre-S1 and pre-S2 mutants transgenic mice will be established and to test whether PPAR agonists and resveratrol could pr