| Project/Area Number |
12671605
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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 |
Obstetrics and gynecology
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
SHIGEMASA kazushi Hiroshima University Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (30294557)
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| Co-Investigator(Kenkyū-buntansha) |
HIRATA eiji Hiroshima University Medical Hospital, Medical staff, 医学部附属病院, 医員
白山 裕子 広島大学, 医学部, 医員
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | ovarian cancer / matrix metalloprotease / serine protease / cell cycle control / apoptosis / MCL-1 / p53 / COX-2 / メタロプロテアーゼ / SCCE / Antileukoprotease / p27 / cyclin E / プロテアーゼ / testisin / MMP-2 / MMP-7 / MMP-9 / TIMP-1 / TIMP-2 |
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| Research Abstract |
(1) Expression of matrix metalloproteinases and their inhibitors in ovarian cancer
We have identified that co-expression of MMP-2, MT1-MMP, and TIMP-2 within the same tumor seems play an important role in the progression of ovarian cancer and that elevated MMP-9 expression together with low expression of TIMP-1 may also contribute to the lymph node metastasis of ovarian carcinoma cells. We also identified that both MMP-2 and MMP-9 is frequently overexpressed in ovarian cancer cells disseminated in the peritoneal cavity and that determination of cellular MMP-2 and MMP-9 expression could potentially be useful in distinguishing cancer cells from mesothelial cells in peritoneal fluid cytological specimens from patients with ovarian epithelial carcinoma.
(2) Determination of serine proteases overexpressed in ovarian cancer
We have identified that the testisin transcript was abundant in ovarian carcinoma but was not detected in normal ovary using Northern blot hybridization. Semi-quantitative P
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CR examination revealed that the testisin mRNA levels in ovarian low malignant potential tumors and in ovarian carcinomas were significantly elevated compared to that in normal ovaries. Testisin overexpression rates in advanced stage diseases were significantly higher than that in early stage diseases in ovarian carcinoma samples. These results suggest that the induction of the testisin transcript may contribute to the development, the progression, and to the invasive / metastatic capacity of ovarian carcinomas. We also examined expression of the protease inhibitor antileukoprotease and the serine protease stratum corneum chymotryptic enzyme (SCCE) in ovarian tumors. Immunohistochemical expression of ALP protein was observed in ovarian tumor cells, whereas little or no staining was observed in normal ovarian surface epithelium. Like SCCE, ALP is highly overexpressed in ovarian tumor cells, which begs the question of whether it remains an effective inhibitor of SCCE of whether it is discordant in time or space and is ineffective as an inhibitor of the SCCE enzyme. Less
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