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Strategy for the development of new therapy for uterine leiomyoma based on the analysis of sex steroidal action in leiomyoma growth

Research Project

Project/Area Number 18390449
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKobe University

Principal Investigator

OHARA Noriyuki (2008)  Kobe University, 医学部附属病院, 准教授 (70214210)

丸尾 猛 (2006-2007)  Kobe University, 大学院・医学系研究科, 教授 (60135811)

Co-Investigator(Kenkyū-buntansha) YOSHIDA Shigeki  神戸大学, 医学部附属病院, 講師 (70294212)
NAKABAYASHI Koji  神戸大学, 医学系研究科, 助教 (80362789)
MATSUO Hiroya  神戸大学, 保健学研究科, 教授 (60229432)
小原 範之  神戸大学, 医学部附属病院, 准教授 (70214210)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥17,410,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2006: ¥8,700,000 (Direct Cost: ¥8,700,000)
Keywords子宮筋腫 / プロゲステロン受容体モデュレーター / アポトーシス / 細胞外基質蛋白 / コラーゲン / 増殖 / SPRM / CDB-2914 / J867 / 筋腫細胞 / Progesterone receptor
Research Abstract

我々は新しい子宮筋腫治療薬として期待されているプロゲステロン受容体モデュレーター(selective progesterone receptor modulator : SPRM)が子宮筋腫細胞において細胞増殖を抑制し、同時にアポトーシスを誘導することを世界に先駆けて明らかにした。今回の研究でSPRMは小胞体ストレス誘導に続いてアポトーシス関連蛋白発現に影響を及ぼしていることを示した。さらに、SPRMが子宮筋腫細胞での細胞外基質蛋白関連蛋白発現を修飾し、コラーゲン生成を抑制させることを初めて明らかにした。SPRMは子宮筋腫の細胞死を誘導し、またコラーゲン合成を抑制することで子宮筋腫発育を抑制している可能性が推測された。

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (42 results)

All 2008 2007 2006 Other

All Journal Article (17 results) (of which Peer Reviewed: 14 results) Presentation (20 results) Book (5 results)

  • [Journal Article] プロゲステロンの実用化の現状2008

    • Author(s)
      小原範之
    • Journal Title

      日本医事新報 No.4386

      Pages: 94-95

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory mechanism of Bcl-2 in uterine leiomyomas2008

    • Author(s)
      Ohara N
    • Journal Title

      Clin Exp Obstet Gynecol 35

      Pages: 1240-241

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Action of progesterone receptor modulators on uterine leiomyomas2008

    • Author(s)
      Ohara N
    • Journal Title

      Clin Exp Obstet Gynecol 35

      Pages: 165-166

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Selective progesterone receptor modulator asoprisnil down-regulates collagen synthesis in cultured human uterine leiomyoma cells through up-regulating extracellular matrix metalloproteinase inducer2008

    • Author(s)
      Morikawa A, Ohara N, Xu Q, Nakabayashi K, DeManno DA, Chwalisz K, Yoshida S, Maruo T
    • Journal Title

      Hum Reprod 23

      Pages: 944-951

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Progesterone receptor modulator CDB-2914 induces extracellular matrix metalloproteinase inducer in cultured human uterine leiomyoma cells2008

    • Author(s)
      Xu Q, Ohara N, Liu J, Amano M, Sitruk-Ware R, Yoshida S, Maruo T
    • Journal Title

      Mol Hum Reprod 14

      Pages: 181-191

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Selective progesterone receptor modulator asoprisnil down-regulates collagen synthesis in cultured human uterine leiomyoma cells through up-regulating extracellularmatrix metalloproteinase inducer2008

    • Author(s)
      Morikawa H, Ohara N, Xu Q, Nakabayashi K, DeManno DA, Chwalisz K, Yoshida s, Maruo T
    • Journal Title

      Hum Reprod 23

      Pages: 944-951

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of progesterone receptor modulator CDB-2914 0n the expression of extracellularmatrix proteins in cultured human uterine leiomyoma cells2008

    • Author(s)
      Xu Q, Ohara N, Liu J, Amano M, Sitruk-Ware R, Yoshida s, Maruo T
    • Journal Title

      Mol Hum Reprod 14

      Pages: 181-191

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective progesterone receptor modulator asoprisnil induces endoplasmic reticulum stress in cultured human uterine leiomyoma cells2007

    • Author(s)
      Xu Q, Ohara N, Liu J, Nakabayashi K, DeManno D, Chwalisz K, Yoshida S, Maruo T
    • Journal Title

      Am J Physiol Endocrinol Metab 293

    • Related Report
      2008 Final Research Report 2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparative effects of SPRM asoprisnil(J867) on proliferation, apoptosis, and the expression of growth factors in cultured uterine leiomyoma cells and normal myometrial cells2007

    • Author(s)
      Ohara N, Morikawa A, Chen W, Wang J, DeManno DA, Chwalisz K, Maruo T
    • Journal Title

      Reprod Sci 14

      Pages: 20-27

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of levonorgestrel-releasing IUS and progesterone receptor modulator PRM CDB-2914 on uterine leiomyomas2007

    • Author(s)
      Maruo T, Ohara N, Matsuo H, Xu Q, Chen W, Sitruk-Ware R, Johansson EDB
    • Journal Title

      Contraception 75

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel selective progesterone receptor modulator Asoprisnil (J867) inhibits proliferation and induces apoptosis in cultured human uterine leiomyoma cells in the absence of comparable effects on myometrial cells2006

    • Author(s)
      Chen W, Ohara N, Wnag J, Xu Q, Liu J, Morikawa A, Sasaki H, Yoshida S, DeManno DA, Chwalisz K, Maruo T
    • Journal Title

      J Clin Endocrinol Metab 91

      Pages: 1296-1304

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A novel selective progesterone receptor modulator Asoprisnil (J867) down-regulates the expression of EGF, IGF-I, TGF β 3, and their receptors in cultured uterine leiomyoma cells2006

    • Author(s)
      Wang J, Ohara N, Wang Z, Chen W, Morikawa A, Sasaki II, DeManno DA, Chwalisz K, Maruo T
    • Journal Title

      Hum Reprod 21

      Pages: 1869-1877

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Progesterone receptor modulator CDB-2914 down-regulates vascular endothelial growth factor, adrenomedullin and their receptors and modulates progesterone receptor content in cultured human uterine leiomyoma cells2006

    • Author(s)
      Xu Q, Ohara N, Chen W, Liu J, Sasaki H, Morikawa A, Sitruk-Ware R, Johansson ED, Maruo T
    • Journal Title

      Hum Reprod 21

      Pages: 2408-2416

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A putative role of versican in uterine leiomyomas

    • Author(s)
      Ohara N
    • Journal Title

      Clin Exp Obstet Gynecol (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sex steroidal modulation of collagen metabolism in uterine leiomyomas

    • Author(s)
      Ohara N
    • Journal Title

      Clin Exp Obstet Gynecol (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Selective progesterone receptor modulator asoprisnil down-regulates collagen synthesis in cultured human uterine leiomyoma cells through up-regulating extracellular matrix metalloproteinase inducer

    • Author(s)
      Morikawa H, Ohara N, Xu Q, Nakabayashi K, DeManno DA, Chwalisz K, Yoshida S, Maruo T
    • Journal Title

      Hum Reprod (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of progesterone receptor modulator CDB-2914 on the expression of extracellular matrix proteins in cultured human uterine leiomyoma cells

    • Author(s)
      Xu Q, Ohara N, Liu J, Amano M, Sitruk-Ware R, Yoshida S, Maruo T
    • Journal Title

      Mol Hum Reprod (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Attack on uterine fibroids by progesterone receptor modulator in a cell-type specific manner2008

    • Author(s)
      Maruo T
    • Organizer
      International Workshop on Uterine Fibroids
    • Place of Presentation
      Germany
    • Related Report
      2008 Final Research Report
  • [Presentation] Attack on uterine fibroids by progesterone receptor modulator in acell-type specific manner2008

    • Author(s)
      Maruo T, et al
    • Organizer
      International Workshop on Uterine Fibroids
    • Place of Presentation
      Berlin, Germany
    • Related Report
      2008 Annual Research Report
  • [Presentation] Progesterone and progesterone receptor modulator in uterine leiomyoma growth. The Oxford-Kobe Biomedical Seminar2007

    • Author(s)
      Maruo T, Matsuo H, Ohara N, Samoto T, Nakago S, Xu Q, Chen W, Wang J
    • Organizer
      International Symposium on Translational Research in Uterine Biology
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2008 Final Research Report
  • [Presentation] Effects of CDB-2914 on ECM expression in cultured leiomyoma cells2007

    • Author(s)
      Maruo T
    • Organizer
      The 91th International Committee Meeting of the Population Council
    • Place of Presentation
      New York, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Selective progesterone receptor modulator asoprisnil induces endoplasmic reticulum stress in cultured uterine leiomyoma cells2007

    • Author(s)
      Xu Q, Ohara N, Liu J, Sasaki H, Morikawa A, Yoshida S, DeManno D, Chwalisz K, Maruo T
    • Organizer
      The 20th Asian and Oceanic Congress of Obstetrics and Gynecology
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2008 Final Research Report
  • [Presentation] Progesterone and progesterone receptor modulator in uterine leiomyoma growth : their implication in reproductive health2007

    • Author(s)
      Maruo T, Matsuo H, Samoto T, Nakago S, Xu Q, Chen W, Wang J, Ohara N
    • Organizer
      The 12th Annual Conference of the Egyptian Fertility and Sterility Society
    • Place of Presentation
      Cairo, Egypt
    • Related Report
      2008 Final Research Report
  • [Presentation] Selective progesterone receptor modulator asoprisnil induces endoplasmic reticulum stress in cultured human uterine leiomyoma cells2007

    • Author(s)
      Xu Q, Ohara N, Liu J, Morikawa A, Sasaki H, Maruo T
    • Organizer
      第59回日本産科婦人科学会
    • Place of Presentation
      京都
    • Related Report
      2008 Final Research Report
  • [Presentation] 子宮筋腫における選択的プロゲステロン受容体モデュレーターJ867のコラーゲン関連タンパク発現への影響の検討2007

    • Author(s)
      森川哲、小原範之、中林幸士、丸尾猛
    • Organizer
      第59回日本産科婦人科学会
    • Place of Presentation
      京都
    • Related Report
      2008 Final Research Report
  • [Presentation] プロゲステロン受容体モデュレーターならびにGnRH antagonistによるヒト子宮筋腫細胞発育制御機構の解析2007

    • Author(s)
      小原範之
    • Organizer
      第59回日本産科婦人科学会
    • Place of Presentation
      京都
    • Related Report
      2008 Final Research Report
  • [Presentation] Progesterone and progesterone receptor modulator in uterine leiomyoma growth: their implication in reproductive health2007

    • Author(s)
      Maruo T, Matsuo H, Samoto T, Nakago S, Xu Q, Chen W, Wang J, Ohara N
    • Organizer
      The 12th Annual Conference of Egyptian Fertility and Sterility Society
    • Place of Presentation
      Cairo, Egypt,
    • Related Report
      2007 Annual Research Report
  • [Presentation] Progesterone and selective progesterone receptor modulator in uterine leiomyoma growth.International Seminar in Reproductive Endocrinology2006

    • Author(s)
      Maruo T, Matsuo H, Xu Q, Chen W, Wang J, Ohara N
    • Place of Presentation
      Siena, Italy
    • Year and Date
      2006-02-28
    • Related Report
      2008 Final Research Report
  • [Presentation] Comparative effects of SPRM asoprisnil(J867)on the proliferation, apoptosis and the expression of growth factors and ECM in cultured uterine leiomyoma cells and normal myometrial cells2006

    • Author(s)
      Maruo T, Ohara N, Morikawa A, Chen W, Wang J, DeManno D, Chwalisz K
    • Organizer
      The 8th International Conference on the Extracellular Matrix of the Female Reproductive Tract
    • Place of Presentation
      Maui, Hawaii, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] In vitro effects of progesterone and progesterone receptor modulator on uterine leiomyoma growth2006

    • Author(s)
      Maruo T, Ohara N, Matsuo H, Nakago S, Yamada T, Chen W, Xu Q, Wang J, Sitruk-Ware R, Johansson EDB
    • Organizer
      The XVIII FIGO World Congress of Gynecology and Obstetrics
    • Place of Presentation
      Kuala Lumpur, Malaysia
    • Related Report
      2008 Final Research Report
  • [Presentation] Progesterone receptor modulator(CDB-2914) induces apoptosis and inhibits proliferation and VEGF expression in cultured uterine leiomyoma cells but not in cultured normal myometrial cells2006

    • Author(s)
      Maruo T, Ohara N, Xu Q, Chen W, Sitruk-Ware R, Johansson EDB
    • Organizer
      The XVIII FIGO World Congress of Gynecology and Obstetrics
    • Place of Presentation
      Kuala Lumpur, Malaysia
    • Related Report
      2008 Final Research Report
  • [Presentation] Comparative effects of progesterone and PRM CDB-2914 on cultured uterine leiomyoma cells and myometrial cells2006

    • Author(s)
      Maruo T, Matsuo H, Ohara N, Xu Q, Chen W, Sitruk-Ware R, Johansson EDB
    • Organizer
      The 89th International Committee Meeting of the Population Council
    • Place of Presentation
      New York, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Effects of CDB-2914 on PR-A and PR-B in leiomyoma and normal myometrium2006

    • Author(s)
      Maruo T
    • Organizer
      The 89th International Committee Meeting of the Population Council
    • Place of Presentation
      New York, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Progesterone and selective progesterone receptor modulator in uterine leiomyoma growth2006

    • Author(s)
      Maruo T, Matsuo H, Samoto T, Shimomura Y, Kurachi O, Nakago S, Yamada T, Xu Q, Chen W, Wang J, Ohara N
    • Organizer
      The 92th Annual Congress of the Korean Society of Obstetrics and Gynecology
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2008 Final Research Report
  • [Presentation] プロゲステロン受容体モデュレーターCDB-2914は培養子宮筋腫細胞におけるVEGF, adrenomedullinとその受容体発現を抑制する2006

    • Author(s)
      徐沁、小原範之、佐々木紘子、陳衛、丸尾猛
    • Organizer
      第58回日本産科婦人科学会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] 選択的プロゲステロン受容体モデュレーターJ867は組織選択的に培養子宮筋腫細胞の増殖を阻害し、アポトーシスを誘導する2006

    • Author(s)
      森川哲、小原範之、陳衛、王佳茵、丸尾猛
    • Organizer
      第58回日本産科婦人科学会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] SPRM asoprisnil(J867)inhibits the proliferation and induces apoptosis in cultured uterine leiomyoma cells but not in cultured normal myometrial cells2006

    • Author(s)
      Maruo T, Ohara N, Chen W, Wang J, DeManno D, Chwalisz K
    • Organizer
      The 12th World Congress of Gynecological Endocrinology
    • Place of Presentation
      Florence, Italy
    • Related Report
      2008 Final Research Report
  • [Book] Translational research in uterine biology2008

    • Author(s)
      Ohara N, Xu Q, Matsuo H, Maruo T
    • Publisher
      Elsevier, Amsterdam, Progesterone and progesterone receptor modulator in uterine leiomyoma growth
    • Related Report
      2008 Final Research Report
  • [Book] 子宮筋腫とSPRM : 子宮筋腫治療の新戦略. Annual Review 糖尿病・代謝・内分泌2008

    • Author(s)
      小原範之、丸尾猛
    • Publisher
      中外医学社
    • Related Report
      2008 Final Research Report
  • [Book] 子宮筋腫研究の最近の話題と今後の展望. 子宮筋腫の臨床2008

    • Author(s)
      小原範之、丸尾猛
    • Publisher
      メジカルビュー社
    • Related Report
      2008 Final Research Report
  • [Book] Progesterone and progesterone receptor modulator in uterine leiomyomagrowth2008

    • Author(s)
      Ohara N, et al
    • Publisher
      Elsevier, Amsterdam
    • Related Report
      2008 Annual Research Report
  • [Book] Translational research in uterine biology2008

    • Author(s)
      Ohara N, Xu Q, Matsuo H, Maruo T
    • Publisher
      Elsevier(In press)
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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