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Immunosuppressive Prednisolone Enhances Early Cholangiocarcinoma in Syrian Hamsters with Liver Fluke Infection and Administration of N-nitrosodimethylamine

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Pathology & Oncology Research

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.

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Acknowledgements

This research was supported by a grant under the program Strategic Scholarships for Frontier Research Network for the Ph.D. Program Thai Doctoral degree from the Office of the Higher Education Commission, Thailand. The authors also gratefully acknowledge financial support from a Grant-in-Aid for Scientific Research (24590504) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and from the Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission, through the Health Cluster (SHep-GMS), Khon Kaen University. We also wish to thank the Department of Parasitology, Liver Fluke and Cholangiocarcinoma Research Center, Animal Experimental Unit, Research Affairs, Faculty of Medicine, Khon Kaen University, for giving the research assistant (AS54301) and their assistance.

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Correspondence to Thidarut Boonmars.

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Juasook, A., Boonmars, T., Wu, Z. et al. Immunosuppressive Prednisolone Enhances Early Cholangiocarcinoma in Syrian Hamsters with Liver Fluke Infection and Administration of N-nitrosodimethylamine. Pathol. Oncol. Res. 19, 55–62 (2013). https://doi.org/10.1007/s12253-012-9557-1

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