Pathogenesis of Liver Fluke Induced Cancer in Thailand

描述（由申请人提供）：人类恶性肿瘤和寄生虫感染之间没有比胆管癌(CCA)-胆管上皮的肝癌-和肝吸虫感染之间的联系更强的联系了。弧菌是致癌物。在整个东亚，在肝吸虫感染流行的地区，CCA的流行率惊人地高。特别是，CCA在泰国东北部非常普遍，那里的生鲤类鱼通常是主食。这些鱼是肝吸虫O. viverrini和华支睾吸虫的中间宿主。在泰国东北部和老挝，尽管广泛使用了抗虫药物吡喹酮，但在一些流行地区，弧菌的流行率接近70%。此外，在泰国，肝癌是最常见的致命肿瘤，在寄生虫流行的地区，CCA的发病率是前所未有的——在美国，CCA约占肝癌的24%，但在泰国孔敬地区，CCA占癌症的87%，是世界上发病率最高的地区。弧菌感染诱导胆管炎症，导致上皮DNA损伤，随后恶性转化为CCA。在感染弧菌的许多人中，有些人严重感染并发展为CCA。本拨款申请的目的是确定o.w verrini的致癌分子，并且，由于一种明显的炎症表型似乎易患CCA，表征那些严重感染o.w verrini的人的炎症表型。加强对猪蛔虫感染患者的免疫学和炎症特征的了解，有助于进行诊断干预，以预防感染和猪蛔虫感染和CCA。这些知识有望指导泰国肝吸虫流行地区的公共卫生政策和提供。此外，研究O. viverrini致癌物质的性质和作用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.