Pathogenesis of Liver Fluke Induced Cancer in Thailand

描述（由申请人提供）：人类恶性肿瘤与寄生虫感染之间的联系没有比胆管癌（CCA）-胆管上皮肝癌-与肝吸虫肝吸虫感染之间的联系更强的联系。O.灵猫蛋白是致癌物质。在整个东亚，肝吸虫感染流行的地区CCA的患病率非常高。特别是，CCA在泰国东北部非常普遍，未煮熟的鲤科鱼通常是主食。这些鱼是肝吸虫O. viverrini和Clonelis sinensis。在泰国东北部和老挝，尽管广泛使用抗蠕虫药物吡喹酮，但O。在某些流行地区，灵猫病的发病率接近70%。此外，在泰国，肝癌是最普遍的致命性肿瘤，在寄生虫流行的地区，CCA的发病率是前所未有的-CCA在美国占肝癌的24%，但在泰国的孔敬地区占癌症的87%，是世界上发病率最高的地区。O.灵猫病毒感染诱导胆管炎症，导致上皮DNA损伤和随后的CCA恶性转化。在众多感染O.灵猫，有些成为严重感染和发展CCA。这项资助申请的目的是鉴定O.并且，由于一种独特的炎症表型似乎易患CCA，因此可以表征严重感染O.维韦里尼。提高对O.灵猫感染应有助于诊断干预，以防止感染和O。灵猫感染和CCA。这方面的知识可以预期指导公共卫生政策和交付在泰国肝吸虫流行的位置。此外，还对O.灵猫蛋白将具有重要的生物医学意义。

DESCRIPTION (provided by applicant): There is no stronger link between a human malignancy and a parasitic infection than the link between cholangiocarcinoma (CCA)-hepatic cancer of the bile duct epithelia-and infection with the liver fluke, Opisthorchis viverrini. O. viverrini is carcinogenic. Throughout East Asia, there is a strikingly high prevalence of CCA in regions where liver fluke infection is endemic. In particular, CCA is extremely prevalent in Northeast Thailand, where uncooked cyprinoid fish is often a dietary staple. These fish are the intermediate hosts of the liver flukes O. viverrini and Clonorchis sinensis. In Northeast Thailand and Laos, despite widespread administration of the anti-worm drug praziquantel, the prevalence of O. viverrini approaches 70% in some endemic areas. Moreover, in Thailand, liver cancer is the most prevalent of the fatal neoplasias, and rates of CCA in regions where the parasite is endemic are unprecedented-CCA is responsible for about 24% of liver cancers in the U.S.A. but represents 87% of cancers in Thailand's Khon Kaen region, the highest incidence in the world. O. viverrini infection induces inflammation of the bile ducts, resulting in DNA damage of the epithelium and subsequent malignant transformation to CCA. Among the many people infected with O. viverrini, some become heavily infected and develop CCA. The objectives of this grant application are to identify the carcinogenic molecules of O. viverrini and, because a distinct inflammation phenotype appears to predispose to CCA, to characterize the inflammation phenotype of those persons who become heavily infected with O. viverrini. Enhanced understanding of immunological and inflammation characteristics of patients with O. viverrini infections should facilitate diagnostic interventions to prevent infection and O. viverrini infection and CCA. This knowledge can be expected to guide public health policy and delivery in liver fluke endemic locations in Thailand. Moreover, characterization of the nature and action of the carcinogens of O. viverrini would be of fundamental biomedical significance.