| Project/Area Number |
10044255
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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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 | FUKUI MEDICAL UNIVERSITY, DEPARTMENT OF OBSTETRICS AND GYNECOLOGY |
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Principal Investigator |
KOTSUJI Fumikazu Fukui Medical University, Dept. of OB/GYN, Professor, 医学部, 教授 (50153573)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Yoshio Fukui Medical University, Dept. of OB/GYN, Instructor, 医学部, 助手 (60220688)
TAJIMA Kimihisa Fukui Medical University, Dept. of OB/GYN, Instructor, 医学部・附属病院, 助手 (60303377)
HOSOKAWA Kumiko Fukui Medical University, Dept. of OB/GYN, Assistant Professor, 医学部, 講師 (60199495)
YONEKURA Yoshiharu Fukui Medical University, Biomedical Imaging Center, Professor, 高エネルギー医学研究センター, 教授 (60135572)
SASAKI Hiromasa Fukui Medical University, Dept. of OB/GYN, Instructor, 医学部, 助手 (20225890)
TSNG Benjami University of Ottawa Department of Obste, Professor
AMSTERDAM Ab The Weizmann Institute of Science Depart, Associate
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1999: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | Granulosa Cell / Differentiation / Apoptosis / Progesterone / Oncogenesis / cisplatin / theophylline / Ovarian Cancer / Xiap / ステロイド産生 / p53 / Mdm2 / シスプラチン / 上皮性卵巣癌細胞 |
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| Research Abstract |
1. Molecular mechanism of steroidogenesis and apoptosis in human granulosa cells.
Using human granulosa cell lines (HO-23), it was confirmed that glucocorticoids and extracellular matrix(ECM) enhanced P4 production while bFGF and phorbol ester TPA suppressed it, that glucocorticoids, ECM and bFGF inhibited p53-induced apoptosis of HO-23 cells while TPA enhanced it, and that apoptosis at early stage does not interrupt steroidogenesis.
2. Establishment of a new treatment strategy for ovarian cancer:
(1) The Efficacy of combination of cisplatin and theophylline:
We have found that cisplatin synergies with theophylline in induction of cell death in human ovarian cancerous cells with mutated p53 and HaRAS (HRP-53) in concentrations lower 3-5 times than these normally administered in ovarian cancer therapy.
(2) We have demonstrated that Xiap down-regulation in p53 wild-type resistant human ovarian cancer cells induces caspase-3-mediated MDM2 processing, leading to increased p53 content and apoptosis. While ineffective alone in p53-mutant cancer cells, suppression of Xiap content by antisense expression can significant enhance the pro-apoptoic effects of wild type-p53 sense expression. In addition, these findings suggest that Xiap may be a novel target.
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