title: Immunosuppressive prednisolone enhances early cholangiocarcinoma in Syrian hamsters with liver fluke infection and administration of N-nitrosodimethylamine.
abstract: Chronic infection with Opisthorchis viverrini for many years has been associated with the development of hepatobiliary diseases including cholangiocarcinoma. It is well known that inflammation is a key component of the tumor microenvironment, and that chronic inflammation plays an important role in tumorigenesis. Therefore, in this study cholangiocarcinogenesis was induced in Syrian hamsters in order to observe the cancer-related inflammation. The Syrian hamsters were divided into 5 groups: uninfected controls; normal Syrian hamsters infected with O. viverrini (OV); immunosuppressed Syrian hamsters infected with O. viverrini (OVis); normal Syrian hamsters infected with O. viverrini and administered N-nitrosodimethylamine (CCA); and immunosuppressed Syrian hamsters infected with O. viverrini and administered N-nitrosodimethylamine (CCAis). Syrian hamster livers were later observed for gross pathology and histopathological changes; COX2 was analyzed by immunohistochemical staining. We found a decreased number of inflammatory cells surrounding the hepatic bile duct in the OVis group, but not in the OV and CCAis groups. However, in the CCAis group (with suppressed immunity) early appearance and greater severity of cholangiocarcinoma were observed; gross pathological examination revealed many cancer nodularities on the liver surface, and histopathological studies showed the presence of cancer cells, findings which correlated with the predominant expression of COX2. The present study suggests that host immune responses are intended to ameliorate pathology, and they are also crucially associated with pathogenesis in O. viverrini infection; the unbalancing of host immunity may enhance cancer-related inflammation.
authors.affiliation: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Amornrat
authors.initials: A
authors.lastname: Juasook
authors.forename: Thidarut
authors.initials: T
authors.lastname: Boonmars
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Wu
authors.forename: Watcharin
authors.initials: W
authors.lastname: Loilome
authors.forename: Kulathida
authors.initials: K
authors.lastname: Veteewuthacharn
authors.forename: Nissana
authors.initials: N
authors.lastname: Namwat
authors.forename: Pakkayanee
authors.initials: P
authors.lastname: Sudsarn
authors.forename: Orasa
authors.initials: O
authors.lastname: Wonkchalee
authors.forename: Pranee
authors.initials: P
authors.lastname: Sriraj
authors.forename: Ratchadawan
authors.initials: R
authors.lastname: Aukkanimart
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D018281:Cholangiocarcinoma / Q000139:chemically induced / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D002908:Chronic Disease; D003043:Cocarcinogenesis; D006224:Cricetinae; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004128:Dimethylnitrosamine; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000469:parasitology / Q000473:pathology; D008099:Liver / Q000737:chemistry / Q000469:parasitology / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000469:parasitology / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D008647:Mesocricetus; D009889:Opisthorchiasis / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D011239:Prednisolone / Q000494:pharmacology*
chemical_list: D007166:Immunosuppressive Agents; D011239:Prednisolone; D051546:Cyclooxygenase 2; D004128:Dimethylnitrosamine