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2007 Fiscal Year Final Research Report Summary

Research for the influence of anti-cancer medicine on ovarian function

Research Project

Project/Area Number 17591718
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionThe University of Tokyo

Principal Investigator

KUGU Koji  The University of Tokyo, The University of Tokyo Hospital, Assistant Professor (30322051)

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)
Project Period (FY) 2005 – 2007
Keywordsovarian function / apoptosis / malignant tumor / anti-cancer drug
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.

  • Research Products

    (59 results)

All 2008 2007 2006 2005

All Journal Article (37 results) (of which Peer Reviewed: 10 results) Presentation (22 results)

  • [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
    • Journal Title

      International Journal of Oncology 32

      Pages: 593-601

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [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
    • Journal Title

      Genes to Cells 13

      Pages: 771-785

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [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
    • Journal Title

      産婦人科治療 96

      Pages: 106-114

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 更年期に関する新しい用語の解説2008

    • Author(s)
      久具宏司
    • Journal Title

      日本更年期医学会ニューズレター 13

      Pages: 22-23

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 卵子提供、精子提供、代理懐胎の実態と問題点2008

    • Author(s)
      久具宏司
    • Journal Title

      日本医師会雑誌 137

      Pages: 53-58

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] GnRHアナログ療法に伴ううつ症状と認知課題中の前頭葉酸素化ヘモグロビン濃度変化との関連2008

    • Author(s)
      河野稔明, 松尾幸治, 矢野哲, 大須賀穣, 久具宏司, 武谷雄二, 綱島浩一
    • Journal Title

      日本更年期医学会雑誌 16

      Pages: 23-30

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 生殖補助医療はどうあるべきか。医療・生命科学の観点から2008

    • Author(s)
      久具宏司, 五十嵐隆, 米本昌平, 水田祥代, 室伏きみ子, 吉村泰典
    • Journal Title

      学術の動向 13

      Pages: 20-31

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] WHIのどの点が見直されているのか2008

    • Author(s)
      大石元, 久具宏司, 矢野哲, 武谷雄二
    • Journal Title

      HORMONE FRONTIER IN GYNECOLOGY 15

      Pages: 191-196

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] GnRH拮抗薬2008

    • Author(s)
      久具宏司
    • Journal Title

      内分泌・糖尿病科 27

      Pages: 123-132

    • Description
      「研究成果報告書概要(和文)」より
  • [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, Kugu K, Yano T, et al
    • Journal Title

      Genes to Cells 13-7

      Pages: 771-785

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] High incidence of tubal dysfunction is determined by laparoscopy in cases with positive Chlamydia trachomatis antibody despite negative finding in prior hysterosalpingography.2007

    • Author(s)
      Hiroi H, Fujiwara T, Nakazawa M, Osuga Y, Momoeda M, Kugu K, Tano T, Tsutsumi O, Taketani Y
    • Journal Title

      Reproductive Medicine and Biology 6

      Pages: 39-43

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [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
    • Journal Title

      Cancer Letters 248

      Pages: 112-122

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 子宮内膜症2007

    • Author(s)
      広田泰, 大須賀穣, 久具宏司, 武谷雄二
    • Journal Title

      産科と婦人科 74

      Pages: 15-19

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 薬物療法における性差医療-抗うつ薬、骨粗難症治療薬、スタテン、排尿障害治療薬、漢方2007

    • Author(s)
      福島寛子, 久具宏司, 矢野哲, 武谷雄二
    • Journal Title

      産科と婦人科 74

      Pages: 465-472

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 骨盤痛の鑑別診断2007

    • Author(s)
      久具宏司, 矢野哲
    • Journal Title

      産婦人科治療 95

      Pages: 388-393

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 産婦人科医の立場から(代理懐胎)2007

    • Author(s)
      久具宏司
    • Journal Title

      産婦人科の世界 59

      Pages: 919-925

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] High incidence of tubal dysfunction is determined by laparoscopy in cases with positive Chlamydia trachomatis antibody despite negative finding in prior hysterosalpingography.2007

    • Author(s)
      Hiroi H, Osuga Y, Kugu K, Yano T, et al
    • Journal Title

      Reproductive Medicine and Biology 6-1

      Pages: 39-43

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Combined phospho-Akt and PTEN expressions associated with post-treatment hysterectomy after conservative progestin therapy in complex atypical hyperplasia and stage Ia, G1 adenocarcinoma of the endometrium.2007

    • Author(s)
      Minaguchi T, Nakagawa S, Osuga Y, Kugu K, Yano T, et al
    • Journal Title

      Cancer Letters 248-1

      Pages: 112-122

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cellular mechanisms of growth inhibition of human endometrial cancer cell line by an antagonist of growth hormone-releasing hormone.2007

    • Author(s)
      Zhao L, Yano T, Osuga Y, Kugu K, et al
    • Journal Title

      International Journal of Oncology 32-3

      Pages: 593-601

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] 更年期医療の現状と未来2006

    • Author(s)
      大石元, 久具宏司, 矢野哲, 武谷雄二
    • Journal Title

      産婦人科治療 93

      Pages: 1-7

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A case of giant cystic adenomyosis.2006

    • Author(s)
      Koga K, Osuga Y, Hiroi H, Oishi H, Kugu K, Yano T, Taketani Y
    • Journal Title

      Fertility and Sterility 85

      Pages: 748-749

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 女性ホルモン補充療法-WHIと今後2006

    • Author(s)
      久具宏司, 矢野哲, 武谷雄二
    • Journal Title

      内分泌・糖尿病科 22

      Pages: 243-250

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] PCOS症例の排卵誘発2006

    • Author(s)
      久具宏司
    • Journal Title

      日本産科婦人科学会雑誌 58

      Pages: N357-361

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 絨毛癌マーカーhCG・SP1を中心に2006

    • Author(s)
      八杉利治, 久具宏司, 武谷雄二
    • Journal Title

      検査と技術 34

      Pages: 1429-1431

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A case of giant cystic adenomyosis.2006

    • Author(s)
      Koga K, Osuga Y, Kugu K, Yano T, et al
    • Journal Title

      Fertility and Sterility 85-3

      Pages: 748-749

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
    • Journal Title

      Endocrinology 146

      Pages: 808-815

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Results of long-term follow-up after treatment of central precocious puberty with leuprorelin acetate : Evaluation of effectiveness of treatment and recovery of gonadal function.2005

    • Author(s)
      Tanaka T, Niimi H, Matsuo N, Fujieda K, Tachibana K, Ohyama K, Satoh M, Kugu K
    • Journal Title

      Journal of clinical Endocrinology and Metabolism 90

      Pages: 1371-1376

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] GnRH II as a possible cytostatic regulator in the development of endometriosis.2005

    • Author(s)
      Morimoto C, Osuga Y, Yano T, Takemura Y, Harada M, Hirata T, Yoshino O, Koga K, Kugu K, Taketani Y
    • Journal Title

      Human Reproduction 20

      Pages: 3212-3218

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Sciatic endometriosis diagnosed by computerized tomography-guided biopsy and GD10 immunohistochemical staining.2005

    • Author(s)
      Koga K, Osuga Y, Harada M, Hirota Y, Yamada H, Akahane M, Kugu K, Taketani Y
    • Journal Title

      Fertility and Sterility 84

      Pages: 1508, e9-12

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 骨盤痛の鑑別診断2005

    • Author(s)
      久具宏司
    • Journal Title

      産婦人科の世界 57

      Pages: 397-311

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 壮年期の骨を守る2005

    • Author(s)
      久具宏司
    • Journal Title

      ホルモンと臨床 53

      Pages: 479-485

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] セトロレリクス2005

    • Author(s)
      久具宏司
    • Journal Title

      Medical Science Digest 31

      Pages: 305-310

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 骨粗鬆症の疫学2005

    • Author(s)
      久具宏司, 矢野哲, 武谷雄二
    • Journal Title

      臨床婦人科産科 59

      Pages: 1074-1079

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cross-talk between Fas/Fas ligand system and nitric oxide in the pathway subserving granulose cell apoptosis : A possible regulatory mechanism for ovarian follicle atresia.2005

    • Author(s)
      Chen Q, Yano T, Osuga Y, Kugu K, et al
    • Journal Title

      Endocrinology 146-2

      Pages: 808-815

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Results of long-term follow-up after treat ment of central precocious puberty with leuprorelin acetate : Evaluation of effectiveness of treatment and recovery of gonadal function. The TAP-144SR Japanese Study Group on central precocious puberty.2005

    • Author(s)
      Tanaka T, Niimi H, Kugu K, et al
    • Journal Title

      The Journal of Clinical Endocrinology an Metabolism 90-3

      Pages: 1371-1376

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] GnRH II as a possible cytostatic regulator in the development of endometriosis.2005

    • Author(s)
      Morimoto C, Osuga Y, Yano T, Kugu K, et al
    • Journal Title

      Human Reproduction 20-11

      Pages: 3212-3218

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Sciatic endometriosis diagnosed by computerized tomography-guided biopsy and CD 10 immunohistochemical staining.2005

    • Author(s)
      Koga K, Osuga Y, Kugu K, et al
    • Journal Title

      Fertility and Sterility 84-5

      Pages: 1508.e9-12

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 多嚢胞性卵巣症候群に対する排卵誘発2008

    • Author(s)
      久具宏司
    • Organizer
      第26回日本受精着床学会学術講演会
    • Place of Presentation
      福岡
    • Year and Date
      20080800
    • Description
      「研究成果報告書概要(和文)」より
  • [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
    • Year and Date
      20080600
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 生殖補助医療における倫理的側面-産婦人科医の考えるべきこと-2008

    • Author(s)
      久具宏司
    • Organizer
      第159回日本産科婦人科学会茨城地方部会例会
    • Place of Presentation
      水戸(茨城)
    • Year and Date
      20080600
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Cellular mechanisms of growth inhibition of human endometrial cancer cell line by type II GnRH.2008

    • Author(s)
      Yano T, ZhaoL, Osuga Y, Kugu K, et al
    • Organizer
      The Endocrine Society 90th Annual Meeting
    • Place of Presentation
      San Francisco CA USA
    • Year and Date
      20080600
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 産婦人科医療の立場から-代理懐胎を考える-2008

    • Author(s)
      久具宏司
    • Organizer
      日本弁護士連合会人権擁護委員会
    • Place of Presentation
      東京
    • Year and Date
      20080200
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 生殖補助医療における倫理的側面(産婦人科医の考えるべきこと)2008

    • Author(s)
      久具宏司
    • Organizer
      第5回熊本女性医学講座
    • Place of Presentation
      熊本
    • Year and Date
      20080200
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 代理懐胎を考える(医療・生命科学の視点から)2008

    • Author(s)
      久具宏司
    • Organizer
      日本学術会議主催公開講演会
    • Place of Presentation
      東京
    • Year and Date
      20080100
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] PCOS例に対する排卵誘発2007

    • Author(s)
      久具宏司
    • Organizer
      第52回日本生殖医学会学術講演会
    • Place of Presentation
      秋田
    • Year and Date
      20071000
    • Description
      「研究成果報告書概要(和文)」より
  • [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
    • Year and Date
      20070900
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Effect of low-dose HRT combined with vitamin K2 or etidronate on bone metabolism.2007

    • Author(s)
      Nakazawa M, Oishi H, Osuga Y, Kugu K, Yano T, et al
    • Organizer
      20th Asian & Oceanic Congress on Obstetrics & Gynecology
    • Place of Presentation
      Tokyo
    • Year and Date
      20070900
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] The change of oxidative stress marker in serum through menstrual cycle2007

    • Author(s)
      Fujiwara T, Goto M, Nakabayashi M, Koyama S, Fujimoto A, Kugu K, Yano T, Tsutsumi O, Taketani Y
    • Organizer
      The Endocrine Society 89th Annual Meeting
    • Place of Presentation
      Toronto, Canada
    • Year and Date
      20070600
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Expression of adiponectin receptors and its possible implication in the human endometrium.2007

    • Author(s)
      Takemura Y, Osuga Y, Kugu K, Yano T, Taketani Y
    • Organizer
      The Endocrine Society 89th Annual Meeting
    • Place of Presentation
      Toronto, Canada
    • Year and Date
      20070600
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] The change of oxidative stress marker in serum through menstrual cycle.2007

    • Author(s)
      Fujiwara T, Goto M, Kugu K, Yano T, et al
    • Organizer
      The Endocrine Society 89th Annual Meeting
    • Place of Presentation
      Toronto Canada
    • Year and Date
      20070600
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Effect of low-dose HRT combined with vitamin K2 or etidronate on bone metabolism.2007

    • Author(s)
      Nakazawa M, Oishi H, Osuga Y, Kugu K, Yano T, et al
    • Organizer
      The Endocrine Society 89th Annual Meeting
    • Place of Presentation
      Toronto Canada
    • Year and Date
      20070600
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 本邦における多嚢胞性卵巣症候群の新しい診断基準について2007

    • Author(s)
      久具宏司
    • Organizer
      第136回日本生殖医学会関東地方部会
    • Place of Presentation
      壬生(栃木)
    • Year and Date
      20070500
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 卵巣予備能の臨床的評価2006

    • Author(s)
      久具宏司
    • Organizer
      第134回日本生殖医学会関東地方部会
    • Place of Presentation
      高崎 (群馬)
    • Year and Date
      20060600
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] PCOS症例の排卵誘発2006

    • Author(s)
      久具宏司
    • Organizer
      第58回日本産科婦人科学会学術講演会
    • Place of Presentation
      横浜(神奈川)
    • Year and Date
      20060400
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Efficacy of low dose HRT with or without other agents.2005

    • Author(s)
      Kugu K
    • Organizer
      19th Asian & Oceanic Congress on OB/GYN
    • Place of Presentation
      Seoul, South Korea
    • Year and Date
      20051000
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 骨盤痛について〜機能性月経困難症を中心に〜2005

    • Author(s)
      久具宏司
    • Organizer
      日本産婦人科医会千葉県支部日本産科婦人科学会千葉地方部会平成17年度秋季合同研修会
    • Place of Presentation
      市川(千葉)
    • Year and Date
      20051000
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Efficacy of low dose HRT with or without other agents. (Symposia : Menopause)2005

    • Author(s)
      Kugu K
    • Organizer
      19th Asian & Oceanic Congress on Obstetrics & Gynecology
    • Place of Presentation
      Seoul Korea
    • Year and Date
      20051000
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Evaluation of insulin resistance using HOMA-IR in obese and non-obese PCOS patients in Japan.2005

    • Author(s)
      Fujiwa T, Takeushi T, Koyam S, Nakabayashi M, Kugu K, Yano T, Tsutsumi O, Taketani Y
    • Organizer
      The Endocrine Society 87th Annual Meeting
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      20050600
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Evaluation of insulin resistance using HOMA-IR in obese and non-obese PCOS patients in Japan.2005

    • Author(s)
      Fujiwara T, Takeuchi T, Kugu K, Yano T, et al
    • Organizer
      The Endocrine Society 87th Annual Meeting
    • Place of Presentation
      San Diego CA USA
    • Year and Date
      20050600
    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2010-06-09  

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