Research for the influence of anti-cancer medicine on ovarian function
| Project/Area Number |
17591718
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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 | The University of Tokyo |
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Principal Investigator |
KUGU Koji The University of Tokyo, The University of Tokyo Hospital, Assistant Professor (30322051)
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| Co-Investigator(Kenkyū-buntansha) |
YANO Tetsu THE UNIVERSITY OF TOKYO, The University of Tokyo Hospital, Associate Professor (90251264)
OSUGA Yutaka THE UNIVERSITY OF TOKYO, The University of Tokyo Hospital, Assistant Professor (80260496)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | ovarian function / apoptosis / malignant tumor / anti-cancer drug |
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| Research Abstract |
Caspases, a family of aspartic acid-specific cysteine proteases, are considered to be death effectors that possess an obligate specificity for cleavage of target proteins at aspartate residues in diverse cell lineages. They take part in the final steps of cell death committal via their unique ability to cleave a wide spectrum of homeostatic proteins. Among these targets are nuclear and cytoskeletal proteins., although it remains to be established whether cleavage of these proteins is required for the execution of all cell deaths.
We further showed that nitric oxide (NO) inhibited Fas/Fas ligand system-induced apoptosis by suppressing activation of the caspases, pointing to a cross-talk between Fas/Fas ligand system-induced apoptosis pathway and NO-mediated antiapoptotic pathway in ovarian follicle atresia through rat granulose cell culture system.
hScrib, human homologue of Drosophila neoplastic tumor suppressor, was identified as a target of human papilloma-virus E6 oncoprotein for the ubiquitin-mediated degradation. We report that hScrib is a novel death substrate targeted by caspase. Full-length hScrib was cleaved by caspase during death ligands-induced apoptosis, which generates a p170 C-terminal fragments in Hela cells. The reported results indicate that caspase-dependent cleavage of hScrib in a critical step for detachment of cell contact during the process of apoptosis.
Further investigations into the mechanisms of ovarian follicle apoptosis on the basis of the present results may bring pathogenesis of ovarian failure into light, which should be a great breakthrough for reproductive medicine.
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Report
(4 results)
Research Products
(70 results)
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[Journal Article] Cellular mechanisms of growth inhibition of human endometrial cancer cell line by an antagonist of growth hormone-releasing hormone.2008
Author(s)
Zhao L, Yano T, Osuga Y, Nakagawa S, Oishi H, Wada-Hiraike O, Tang X, Yano N, Kugu K, Schally AV, Taketani Y
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Journal Title
International Journal of Oncology 32
Pages: 593-601
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] hScrib, a human homologue of Drosophila neoplastic tumor suppressor, is a novel death substrate targeted by caspase during the process of apoptosis.2008
Author(s)
Sone K, Nakagawa S, Nakagawa K, Takizawa S, Matsumoto Y, Nagasaka K, Tsuruga T, Hiraike H, Hiraike-Wada O, Miyamoto Y, Oda K, Yasugi T, Kugu K, Yano T, Taketani Y
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Journal Title
Genes to Cells 13
Pages: 771-785
Description
「研究成果報告書概要(和文)」より
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[Journal Article] 全自動化学発光免疫測定法を原理としたARCHITECT[○!R]アナライザーi2000[○!R]こよる下垂体・性腺ホルモン6項目測定法の臨床的検討2008
Author(s)
苛原稔, 松崎利也, 藤井俊策, 水沼英樹, 内田浩, 吉村泰典, 久具宏司, 武谷雄二, 高橋健太郎, 野田洋一, 松尾隆志, 堂地勉
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[Journal Article] Combined phospho-Akt and PTEN expressions associated with posttreatment hysterectomy after conservative progestin therapy in complex atypical hyperplasia and stage Ia, G1 adenocarcinoma of the endometrium.2007
Author(s)
Minaguchi T, Nakagawa S, Takazawa Y, Nei T, Horie K, Fujiwara T, Osuga Y, Yasugi T, Kugu K, Tano T, Yoshikawa H, Taketani Y
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Journal Title
Cancer Letters 248
Pages: 112-122
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Cross-talk between Fas/Fas ligand system and nitric oxide in the path-way subserving granulose cell apoptosis : A possible regulatory mechanism for ovarian follicle atresia2005
Author(s)
Chen Q, Yano T, Matsumi H, Osuga Y, Yano N, Xu J, Wada O, Koga K, Fuiiwara T, Kugu K, Taketani Y
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Journal Title
Endocrinology 146
Pages: 808-815
Description
「研究成果報告書概要(和文)」より
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[Presentation] Cellular mechanisms of growth inhibition of human endometrial cancer cell line by type II GnRH.2008
Author(s)
Yano T, Zhao L, Osuga Y, Nakagawa S, Oishi H, Wada-Hiraike O, Yano N, Kugu K, Taketani Y
Organizer
The Endocrine Society 90th Annual Meeting
Place of Presentation
San Francisco, CA, USA
Description
「研究成果報告書概要(和文)」より
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[Presentation] Effect of low-dose HRT combined with vitamin K2 or etidronate on bone metabolism.2007
Author(s)
Nakazawa M, Oishi H, Fukushima H, Fujiwara T, Osuga Y, Momoeda M, Kugu K, Takeuchi T, Yano T, Taketani Y
Organizer
20th Asian & Oceanic Congress on Obstetrics and Gynecology
Place of Presentation
Tokyo, Japan
Description
「研究成果報告書概要(和文)」より
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