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Exploration of molecular targets for endometriosis-associated ovarian cancer with in vitro multistep carcinogenesis model

Research Project

Project/Area Number 23390387
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

KYO Satoru  金沢大学, 医学系, 准教授 (50272969)

Co-Investigator(Kenkyū-buntansha) TAKAKURA Masahiro  金沢大学, 大学病院, 助教 (20313661)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2013: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2011: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Keywordschocolate cyst / endometriosis / ovarian cancer / immortalization / carcinogenesis / 卵巣チョコレート嚢腫 / 癌化 / 不死化 / 子宮内膜症 / チョコレート嚢胞 / 内膜症 / 上皮細胞 / テロメレース
Research Abstract

To more understand the molecular mechanisms of ovarian carcinogenesis arising from ovarian endometrioma, we first established the immortalized epothelial cells from ovarian endometrioma via overexpressing cyclinD1/cdk4/hTERT cDNA. Based on the genetic analyses of clinical samples, we introduced several genetic factors into these cells to observe the transformed phenotypes. Introduction of dominant negative p53, oncogenic K-ras alleles, together with c-myc overexpression, enabled cells to obtain transformed phenotypes. These 3 steps appeared to be essential for ovarian carcinogenesis associated with endometriosis and thereby will be a promissing molecular target for the novel treatment modality.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (25 results)

All 2014 2013 2012 2011 Other

All Journal Article (21 results) (of which Peer Reviewed: 21 results) Presentation (4 results)

  • [Journal Article] The PRB-dependent FOXO1/IGFBP-1 axis is essential for progestin to inhibit endometrial epithelial growth2013

    • Author(s)
      Nakamura M, Takakura M, Fujii R, Maida Y, Bono Y, Mizumoto Y, Zhang X, Kiyono T and Kyo S
    • Journal Title

      Cancer Lett

      Volume: 336 Pages: 68-75

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of signal transducer and activator of transcription-3 in cell-cell interactions of peritoneal macrophages and endometrial stromal cells in human endometriosis2013

    • Author(s)
      Itoh F, Komohara Y, Takaishi K, Honda R, Tashiro H, Kyo S, Katabuchi H, Takeya M
    • Journal Title

      Fertil Steril

      Volume: 99 Pages: 1705-1713

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Establishment and Characterization of Immortalized Human Amniotic Epithelial Cells2013

    • Author(s)
      Zhou K, Koike C, Yoshida T, Okabe M, Fathy M, Kyo S, Kiyono T, Saito S, Nikaido T
    • Journal Title

      Cell Reprogram

      Volume: 15 Pages: 55-67

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Endometrial cancer stem cells : Are they a possible therapeutic target?2013

    • Author(s)
      Kyo S
    • Journal Title

      Curr.Obstet.Gynecol.Rep

      Volume: 2 Pages: 1-10

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Plasma Membrane proteomics identifies bone marrow stromal antigen 2 as a potential therapeutic target in endometrial cancer2013

    • Author(s)
      Yokoyama T, Enomoto T, Serada S, Morimoto A, Matsuzaki S, Ueda Y, Yoshino K, Fujita M, Kyo S, Iwahori K, Fujimoto M, Kimura T and Naka T
    • Journal Title

      Int.J .Cancer

      Volume: 132 Pages: 472-484

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of Immortalized Human Amniotic Mesenchymal Stem Cells2013

    • Author(s)
      Teng Z, Yoshida T, Okabe M, Toda A, Higuchi O, Nogami M, Yoneda N, Zhou K, Kyo S, Kiyono T, Nikaido T
    • Journal Title

      Cell Transplant

      Volume: 22 Pages: 267-278

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Circulating tumor cells detected by a novel adenovirus-mediated system may be a potent therapeutic marker in gynecologic cancers2012

    • Author(s)
      Takakura M, Kyo S, Nakamura M, Maida Y, Mizumoto Y, Bono Y, Zhang X, Hashimoto Y, Urata Y, Fujiwara T and Inoue M
    • Journal Title

      Br.J .Cancer

      Volume: 107 Pages: 448-454

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protease-activated receptor-stimulated interleukin-6 expression in endometriosis-like lesions in an experimental mouse model of endometriosis2012

    • Author(s)
      Shinohara A, Kutsutake M, Takahashi M, Kyo S, Tachikawa E and Tamura K
    • Journal Title

      J .Pharmacol. Sci

      Volume: 19 Pages: 40-51

    • NAID

      10030760253

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Massive hemothorax due to diaphragmatic endometriosis after a laparoscopic cystectomy of an ovarian endometrioma in a patient without a history of thoracic endometriosis2012

    • Author(s)
      Kyo S, Takakura M, Nishida S, Ozaki S, Oda M and Inoue M
    • Journal Title

      Arh.Gynecol.Obstet

      Volume: 286 Pages: 411-414

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Creation of immortalized epithelial cells from ovarian endometrioma2012

    • Author(s)
      Bono Y, Kyo S, Takakura M, Maida Y, Mizumoto Y, Nakamura M, Nomura K, Kiyono T and Inoue M
    • Journal Title

      Br.J .Cancer

      Volume: 103 Pages: 1205-1213

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Creation of immortalized epithelial cells from ovarian endometrioma.2012

    • Author(s)
      Yukiko Bono
    • Journal Title

      British Journal of Cancer

      Volume: 103 Pages: 1205-1213

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Creation of immortalized epithelial cells from ovarian endometrioma2012

    • Author(s)
      Bono Y, Kyo S, et al.
    • Journal Title

      British Journal of Cancer

      Volume: (in press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dienogest inhibits Toll-like receptor 4 expression induced by co-stimulation of lipopolysaccharide and high-mobility group box 1 in endometrial epithelial cells Fertil2011

    • Author(s)
      Mita S, Shimizu Y, Notsu T, Imada K, Kyo S
    • Journal Title

      Steril

      Volume: 96 Pages: 1485-1489

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Frequency of myeloid dendritic cells can predict the efficacy of wilms' tumor 1 Peptide vaccination2011

    • Author(s)
      Ohno S, Takano F, Ohta Y, Kyo S, Myojo S, Dohi S, Sugiyama H, Ohta T, Inoue M
    • Journal Title

      Anticancer Res

      Volume: 31 Pages: 2447-2452

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] WT1 Peptide Vaccine Stabilized Intractable Ovarian Cancer Patient for One Year : A Case Report2011

    • Author(s)
      Dohi S, Ohno S, Ohno Y, Takakura M, Kyo S, Soma G, Sugiyama H, Inoue M
    • Journal Title

      Anticancer Res

      Volume: 31 Pages: 2441-2445

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Stem cells in endometrium and endometrial cancer : Accumulating evidence and unresolved questions2011

    • Author(s)
      Kyo S, Maida Y and Inoue M
    • Journal Title

      Review article. Cancer Letters

      Volume: 308 Pages: 123-133

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phase I Clinical Study of the Dietary Supplement, Agaricus blazei Murill, in Cancer Patients in Remission2011

    • Author(s)
      Ohno S, Sumiyoshi Y, Hashine K, Shirato A, Kyo S and Inoue M
    • Journal Title

      Evid Based Complement Alternat Med

      Volume: vol. 2011, Article ID 192381 Issue: 1 Pages: 9-9

    • DOI

      10.1155/2011/192381

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activation of NF-κB is a novel target of KRAS-induced endometrial carcinogenesis2011

    • Author(s)
      Mizumoto Y, Kyo S, Kiyono T, Takakura M, Nakamura M, Maida Y, Mori N, Bono Y, Sakurai H and Inoue M
    • Journal Title

      Clin. Cancer Res

      Volume: 17 Pages: 1341-1350

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] a synthetic progestine, inhibits prostaglandin E2 production and aromatase expression by human endometrial epithelial cells in a sheroid culture system2011

    • Author(s)
      Shimizu Y, Mita S, Takeuchi T, Notsu T, Mizuguchi K, Kyo S. Dianogest
    • Journal Title

      Steroids

      Volume: 76 Pages: 60-67

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Forkhead transcription factor FOXO1 is a direct target of progestin to inhibit endometrial epithelial cell growth2011

    • Author(s)
      Kyo S, Sakaguchi J, Kiyono T, Shimizu Y, Maida Y, Mizumoto Y, Mori N, Nakamura M, Takakura M, Miyake M, Sakamoto M and Inoue M
    • Journal Title

      Clin.Cancer Res

      Volume: 17 Pages: 525-537

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Forkhead transcription factor FOXO1 is a direct target of progestin to inhibit endometrial epithelial cell growth2011

    • Author(s)
      Kyo S, Sakaguchi J, et al.
    • Journal Title

      Clin.Cancer Res.

      Volume: 15 Pages: 525-537

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] 卵巣チョコレート嚢胞の in vitro 癌化モデルの作成と癌化経路の解析2014

    • Author(s)
      京 哲
    • Organizer
      第13回婦人科癌分子標的研究会
    • Place of Presentation
      米子
    • Year and Date
      2014-03-15
    • Related Report
      2013 Final Research Report
  • [Presentation] 卵巣チョコレート嚢胞不死化細胞を用いた癌化モデルの作成と発がん分子機構の解析2014

    • Author(s)
      保野由紀子, 京哲, 高倉正博, 中村充宏, 水本泰成, 宮川純奈, 藤原浩
    • Organizer
      第35回エンドメトリオージス学会
    • Place of Presentation
      鹿児島
    • Year and Date
      2014-01-25
    • Related Report
      2013 Final Research Report
  • [Presentation] 子宮内膜症細胞の安定培養系の確率とその研究応用2013

    • Author(s)
      京 哲
    • Organizer
      第34回日本エンドメトリオージス学会 イブニングセミナー
    • Place of Presentation
      宇都宮
    • Year and Date
      2013-01-18
    • Related Report
      2013 Final Research Report
  • [Presentation] 卵巣チョコレート嚢胞不死化細胞を用いた癌化モデルの作成と発がん分子機構の解析

    • Author(s)
      保野由紀子、京哲、高倉正博、中村充宏、水本泰成、 張秀智、宮川純奈、藤原浩
    • Organizer
      第35回日本エンドメトリオーシス学会
    • Place of Presentation
      鹿児島県鹿児島市 城山観光ホテル
    • Related Report
      2013 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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