The Regin-Angiotensin System in Hepatitis and Hepatoma

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Mary Maluccio is a board certified surgical oncologist. She has recently secured a tenure track position at Indiana University. Her immediate career goal is to set up a productive laboratory research environment. Her long term career goals include: 1) leading clinical research protocols based on observations made in the laboratory and 2) increasing her presence within the cancer research community. With a concentrated effort in an academic environment committed to supporting a translational research approach, she feels that she has the potential to put together solid R01 grant applications for research protocols that will not only help answer questions about cancer biology, but change the way we treat cancer patients. Her clinical and basic science interests currently focus on studies investigating hepatocellular carcinoma biology and the impact of the stromal cells on the malignant phenotype. Primary liver cancer is a worldwide problem with limited therapies and a pathophysiology that remains unclear. An investigation into the role of the renin-angiotensin system in hepatitis and the development of hepatocellular cancer is something completely novel. The primary objectives of the proposal are 1) to use an established preclinical model of hepatitis associated cancer to investigate the stromal influence and molecular mechanisms associated with hepatocellular tumorigenesis, 2) to investigate the influence of the renin-angiotensin system and the consequences of AII receptor signal transduction on tumor growth 3) determine the level of expression and localization of renin-angiotensin system elements in liver tissue and tumors of patients with hepatitis and hepatocellular cancer, and 4) to determine if there is a link between the renin-angiotensin system and tumor growth that would expose a novel therapeutic target. This study entails the use of human liver specimens from the patients along a continuum of hepatitis related liver disease (stage 0 through stage 4), including patients with hepatitis who have developed hepatocellular carcinoma. The preclinical model involves a human hepatitis derived hepatocellular carcinoma xenograft into an immunodeficient mouse.