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Hepcidin/ferroportin expression levels involve efficacy of pegylated-interferon plus ribavirin in hepatitis C virusinfected liver

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World Journal of Gastroenterology 2015年第11期21卷 3291-3299页

作者： Motoyuki Kohjima Tsuyoshi Yoshimoto Munechika Enjoji Nobuyoshi Fukushima Kunitaka Fukuizumi Tsukasa Nakamura Miho Kurokawa Nao Fujimori yusuke Sasaki Yasushi Shimonaka yusuke murata Susumu Koyama Ken Kawabe Kazuhiro Haraguchi Yorinobu Sumida Naohiko Harada Masaki Kato Kazuhiro Kotoh Makoto Nakamuta Department of Gastroenterology and Clinical Research Center National Hospital Organization Kyushu Medical Center Health Care Center Fukuoka University Product Research Department Chugai Pharmaceutical Co.Ltd. Department of Medicine and Bioregulatory Science Kyushu University

AIM:To investigate the relationship between the ironmetabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C ***:The hepatic expression profile of ironmetabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated.A hundred patients with chronic hepatitis C(genotype1b,n = 50; genotype 2,n = 50) were enrolled and retrospectively *** biopsy samples were subjected to quantitative polymerase chain reaction for iron-metabolismrelated genes and protein expression(Western blotting analysis) for *** a control,normal liver tissue was obtained from 18 living donors of liver *** hepcidin level was measured by sensitive liquid chromatography/electrospray ionization tandem mass ***:Iron overload is associated with liver damage by increasing oxidative stress and hepatitis C virus(HCV)is reported to induce iron accumulation in hepatocytes in ***,iron administration suppresses HCV replication in ***,the association between HCV infection and iron metabolism remains *** with controls,patients had significantly higher gene expression for transferrin,iron-regulatoryproteins 1 and 2,divalent metal transporter 1,and ferroportin,but similar for transferrin receptors 1 and2,and *** the expression profiles were compared between sustained virological response(SVR)and non-SVR patients,the former showed significantly lower transcription and protein expression of hepcidin and *** of hepcidin-regulating genes,BMPR1,BMPR2,and hemojuvelin,was significantly increased,whereas BMP2 was decreased in HCV-infected ***2 and hemojuvelin expression was significantly lower in the SVR than non-SVR *** infection affects the expression of iron-metabolism-related genes,leading to iron accumulation in ***:Decrea

关键词： Chronic hepatitis C Iron-metabolism Hepcidin Ferro

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Nitrative and oxidative DNA damage in intrahepatic cholangiocarcinoma patients in relation to tumor invasion

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World Journal of Gastroenterology 2005年第30期11卷 4644-4649页

作者： Somchai Pinlaor Banchob Sripa Ning Ma yusuke Hiraku Puangrat Yongvanit Sopit Wongkham Chawalit Pairojkul Vajarabhongsa Bhudhisawasdi Shinji Oikawa Mariko murata Reiji Semba Shosuke Kawanishi Department of Parasitology Department of Pathology Department of Anatomy Department of Environmental and Molecular Medicine Department of Biochemistry Department of Surgery

AIM： Nitrative and oxidative DNA damage such as 8-nitroguanine and 8-oxo-7,8-dihydro-2＇-deoxyguanosine （8-oxodG） formation has been implicated in initiation and/ or promotion of inflammation-mediated carcinogenesis. The aim of this study is to clarify whether these DNA lesions participate in the progression of intrahepatic cholangiocarcinoma. METHODS： We investigated the relation of the formation of 8-nitroguanine and 8-oxodG and the expression of hypoxia-inducible factor-1α （HIF-1α） with tumor invasion in 37 patients with intra-hepatic cholangiocarcinoma. RESULTS： Immunohistochemical analyses revealed that 8-nitroguanine and 8-oxodG formation occurred to a much greater extent in cancerous tissues than in non-cancerous tissues. HIF-1α could be detected in cancerous tissues in all patients, suggesting low oxygen tension in the tumors. HIF-1α expression was correlated with inducible niltric oxide synthase （iNOS） expression （r = 0.369 and P = 0.025） and 8-oxodG formation （r = 0.398 and P = 0.015）. Double immunofluorescence study revealed that iNOS and HIF-1α co-localized in cancerous tissues. Notably, the formation of 8-oxodG was correlated significantly with lymphatic invasion （r = 0.386 and P = 0.018）. Moreover, 8- nitroguanine and 8-oxodG in non-cancerous tissues were associated significantly with neural invasion （P = 0.042 and P = 0.026, respectively）. These results suggest that reciprocal activation between HIF-1α and iNOS mediates persistent DNA damage, which induces tumor invasiveness via mutations, resulting in poor prognosis. CONCLUSION： The formation of 8-nitroguanine and 8-oxodG plays an important role in multiple steps of genetic changes leading to tumor progression, including invasiveness.

关键词： 8-Nitroguanine 8-Oxo-7,8-dihydro-2'-deoxyguanosine Hypoxia-inducible factor-1α Cholangiocarcinoma Tumor invasion

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