Inhibition of EP1 in conjunction with Sorafenib for liver cancer chemoprevention

抑制 EP1 与索拉非尼联合用于肝癌化学预防

• 批准号: 8057487
• 负责人: Chang Han
• 金额: $ 6万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-20 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8057487
• 关键词: BAY 54-9085; Malignant neoplasm of liver; cancer chemoprevention

DESCRIPTION (provided by applicant): Primary liver cancers are highly malignant tumors in human and their incidences are rising in the United States. The overall survival of patients with liver cancer is grim and currently no efficient chemoprevention is available. On the basis of our published and ongoing studies, we hypothesize that the EP1 receptor plays a key role in prostaglandin-induced hepatic carcinogenesis and that inhibition of EP1 in combination with the multikinase inhibitor, sorafenib, may represent a novel and safe approach for effective chemoprevention. This hypothesis will be examined in the two specific aims using complementary animal models of hepatic carcinogenesis. Aim 1 will evaluate the combination effect of EP1 inhibition and sorafenib on the development of hepatocellular cancer induced by the hepatic carcinogen, diethylnitrosamine. Aim 2 will examine the combination effect of EP1 inhibition and sorafenib on the development of intrahepatic cholangiocellular carcinoma induced by Pten/Smad4 disruption. The proposed studies are expected to provide important implications for future chemoprevention of human liver cancer.

描述（由申请人提供）： 原发性肝癌是人类的高度恶性肿瘤，其发病率在美国呈上升趋势。肝癌患者的总体生存状况严峻，目前尚无有效的化学预防方法。根据我们已发表和正在进行的研究，我们假设 EP1 受体在前列腺素诱导的肝癌发生中发挥关键作用，并且与多激酶抑制剂索拉非尼联合抑制 EP1 可能代表一种新颖且安全的有效化学预防方法。该假设将使用肝癌发生的互补动物模型在两个特定目标中进行检验。目标 1 将评估 EP1 抑制和索拉非尼对肝癌致癌物二乙基亚硝胺诱导的肝细胞癌发展的联合作用。目标 2 将检查 EP1 抑制和索拉非尼对 Pten/Smad4 破坏诱导的肝内胆管细胞癌发展的联合作用。拟议的研究预计将为未来人类肝癌的化学预防提供重要意义。