2002 Fiscal Year Final Research Report Summary
Cytochrome P450 and Cyclooxygenease-2 expression in liver tissue surrounding hepatocellur carcinoma : Evaluation of environmental state of multicentric hepatocarcinogenesis
| Project/Area Number |
13671283
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
ITO Hiroshi Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (00232463)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDOME Hiroyuki Chiba University, University Hospital, Assistant, 医学部附属病院, 助手 (10312935)
ISHIKURA Hiroshi Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (70222982)
MIYAZAKI Masaru Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (70166156)
OHTSUKA Masayuki Chiba University, University Hospital, Assistant, 医学部附属病院, 助手 (90334185)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Hepatocellular Carcinoma / Carcinogenesis / Oxidative Stress / Cytochrome P450 / Cyclooxygenase-2 / Multicentric Occurrence |
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| Research Abstract |
BACKGROUND. Hepatocellular carcinoma (HCC) usually originates in chronic hepatitis or liver cirrhosis. Cyclooxygenase-2 (COX-2), a key enzyme in the conversion of arachidonic acid to prostaglandins, and cytochrome P450 (CYP), xenobiotics metabolizing enzymes, are said to be involved in carcinogenesis. In this study, we explored if COX and CYP expression in injured liver tissue was involved in hepatocarcinogenesis, especially multicentric occurrence of HCC.
METHODS. The expression of cyclooxygenase-2 (COX-2) and cytochrome P450 (CYP) in liver tissues from surgical specimens were immunohistochemically examined, and malondialdehyde (MDA) level in liver tissue was also determined.
RESULTS. COX-2 expression in liver tissue surrounding tumor was significantly higher in cases with HCC than in cases with normal liver, and the expression rate of COX-2 grew higher in proportion to degree of fibrosis. There was no difference between cases with HCC and those with normal liver as regards CYP isoform expression in liver tissue surrounding tumors. With all CYP isoforms, the co-expression rate of COX-2 and CYP tended to be higher in cases with HCC than in cases with normal liver, and the co-expression rate of COX-2 and CYP2E1 was significantly higher in the multicentric occurrence (MO) group than in the non-multicentric occurrence (non-MO) group. Moreover, the MDA volume was significantly higher in the MO group (0.633 ± 0.473 μg/mg protein) than in the non-MO group (0.303 ± 0.257, p<0.05).
CONCLUSIONS. Our data suggest that COX-2 and CYP may influence the hepatocarcinogenesis, especially in their multicentric occurrence.
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[Publications] Kataoka M, Shimizu H, Mitsuhashi N, Ohtsuka M, Wakabayashi Y, Ito H, Kimura F, Nakagawa K, Yoshidome H, Shimizu Y, Miyazaki M: "Effect of cold ischemia time on C-X-C chemokine expression and neutrophil accumilation in the graft live after orthotopic liver transplantation in rats"Transplantation. 73. 1730-1735 (2002)
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