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Hypoxic cytotoxin TX-402 might inhibit the expansion of cancer stem cells in ovarian cancer.

Research Project

Project/Area Number 23592443
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionGifu University

Principal Investigator

MORISHIGE Ken-ichirou  岐阜大学, 医学(系)研究科(研究院), 教授 (90283788)

Co-Investigator(Kenkyū-buntansha) ITO Naoki  岐阜大学, 医学部附属病院, 講師 (30184675)
FURUI Tatsurou  岐阜大学, 大学院医学系研究科, 准教授 (00313883)
TOYOKI Hiroshi  岐阜大学, 医学部附属病院, 講師 (40402169)
HAYASAKI You  岐阜大学, 大学院医学系研究科, 助教 (20566492)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Keywords卵巣癌 / 癌幹細胞 / 低酸素 / HIF / がん幹細胞
Research Abstract

In the solid tumor, the region away from the vasculatures are hypoxic and recent studies have revealed that hypoxia inducible factor (HIF) increases the fraction of cancer stem cells (CSCs). TX-402, developed as a hypoxic cytotoxin, inhibited the expression of HIF.We supposed that TX-402 might be a possible candidate as a molecular-targeted drug for ovarian cancer by inhibiting CSC expansion. Hypoxia induced the expression of HIF, stem cell factors, and putative CSC markers. Furthermore, TX-402 inhibited these stem cell factors and CSC markers, dose-dependently.
Next, we constructed the spheroids of ovarian cancer cell line, as a 3D hypoxia model, in which the internal hypoxic region contained CSCs. These hypoxic regions containing CSCs was disappeared by the treatment with TX-402.In conclusion, hypoxia might promote the expansion of CSCs, and TX-402 could be useful for ovarian cancer by inhibiting the hypoxia-induced CSC expansion.

Report

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

    (22 results)

All 2014 2013 2012 2011

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (12 results)

  • [Journal Article] Diffusion-weighted Imaging of Ovarian Torsion: Usefulness of Apparent Diffusion Coefficient (ADC) Values for the Detection of Hemorrhagic Infarction2014

    • Author(s)
      Kato H, Kanematsu M, Uchiyama M, Yano R, Furui T, Morishige KI
    • Journal Title

      Magn Reson Med Sci

      Volume: 13 Pages: 39-44

    • NAID

      130003392989

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An Impact of the Specialization in gynecology and obstetrics departments on pregnant women's choice for maternity institutions2013

    • Author(s)
      Adachi Y, Iso H, Shen J, Ban K, Fukui O, Hashimoto H, Nakashima T, Morishige K, Saijo T
    • Journal Title

      Health Economics Review

      Volume: 3(1) Issue: 1 Pages: 31-31

    • DOI

      10.1186/2191-1991-3-31

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] MR imaging findings with emphasis on intratumoral cyst formation2013

    • Author(s)
      Kato H, Kanematsu M, Ono H, Yano R, Furui T, Morishige KI, Hatano Y
    • Journal Title

      Eur J Radiol

      Volume: 82 Issue: 9 Pages: 417-421

    • DOI

      10.1016/j.ejrad.2013.04.010

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] miR-92a inhibits peritoneal dissemination of ovarian cancer cells by inhibiting integrin α5 expression2013

    • Author(s)
      Ohyagi-Hara C, Sawada K, Mabuchi S, Takahashi T, Kurachi H
    • Journal Title

      Am J Pathol

      Volume: 182(5) Issue: 5 Pages: 1876-1889

    • DOI

      10.1016/j.ajpath.2013.01.039

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ovarian mucinous cystadenoma coexisting with benign Brenner tumor: MR imaging findings2013

    • Author(s)
      Kato H, Kanematsu M, Furui T, Morishige KI, Hirose Y
    • Journal Title

      Abdom Imaging

      Volume: 38 Issue: 2 Pages: 412-416

    • DOI

      10.1007/s00261-012-9887-1

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A Cost-Benefit Analysis on the Specialization in Departments of Obstetrics and Gynecology in Japan2012

    • Author(s)
      Junyi Shen, On Fukui, Hiroyuki Hashimoto, Takako Nakashima, Tadashi Kimura, Kenichiro Morishige and Tatsuyoshi Saijo
    • Journal Title

      Health Economics Review

      Volume: 2(1) Issue: 1 Pages: 2-2

    • DOI

      10.1186/2191-1991-2-2

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Integrin Inhibitors as a Therapeutic Agent for Ovarian Cancer2012

    • Author(s)
      Sawada K, Ohyagi-Hara C, Kimura T Morishige K-I
    • Journal Title

      J Oncol

      Volume: 2012 Pages: 915140-915140

    • DOI

      10.1155/2012/915140

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Postpartum hemorrhage in coagulopathic patients: Preliminary experience with uterine arterial embolization with N-butyl cyanoacrylate2011

    • Author(s)
      Kanematsu M, Watanabe H, Kondo H, Goshima S, Kato H, Furui T, Toyoki H, Morishige K
    • Journal Title

      J Vasc Interv Radiol

      Volume: 22 Issue: 12 Pages: 1773

    • DOI

      10.1016/j.jvir.2011.08.016

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chemotherapy for endometrial carcinoma (GOGO-EM1study):TEC(paclitaxel, epirubicin and carboplatin) is an effective remission-induction and adjuvant therapy2011

    • Author(s)
      Egawa-Takata T, Ueda Y, Fujita M, Yoshino K, Enomoto T
    • Journal Title

      Cancer Chemother Pharmacol

      Volume: 68 Issue: 6 Pages: 1603-10

    • DOI

      10.1007/s00280-011-1638-4

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Postoperative whole pelvic radiotherapy plus concurrent chemotherapy versus extended-field irradiation for early-stage cervical cancer patients with multiple pelvic lymph node metastases2011

    • Author(s)
      Mabuchi S, Okazawa M, Isohashi F, Ohta Y, Maruoka S, Yoshioka Y, Enomoto T, Morishige K, Kamiura S, Kimura T
    • Journal Title

      Gynecol Oncol

      Volume: 120(1) Issue: 1 Pages: 94-100

    • DOI

      10.1016/j.ygyno.2010.09.016

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] Relationship between therapy for uterine cervical cancer and body composition on premenopausal women2013

    • Author(s)
      Kawashima E, Sugiyama M, Misao A, Fujimoto J, Morishige K-I
    • Organizer
      The 5th Scientific Meeting of the Asia Pacific Menopause Federation
    • Place of Presentation
      Japan, Tokyo
    • Related Report
      2013 Final Research Report
  • [Presentation] Relationship between therapy for uterine cervical cancer and body composition on premenopausal women2013

    • Author(s)
      Kawashima E, Sugiyama M, Misao A, Fujimoto J, Morishige K-I
    • Organizer
      The 5th Scientific Meeting of the Asia Pacific Menopause Federation
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] 卵巣明細胞がんにおける癌幹細胞マーカーALDH1の関与2012

    • Author(s)
      水野智子、牧野弘、鈴木紀子、小倉寛則、森重健一郎
    • Organizer
      第50回日本癌治療学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 卵巣癌におけるHIF-1阻害剤によるcancer stem cell-like cellの増大抑制効果に関する検討2012

    • Author(s)
      鈴木紀子、小倉寛則、永澤秀子、森重健一郎
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] 当科における上皮性卵巣癌の再発後長期生存例の検討2012

    • Author(s)
      牧野弘、小倉寛則、森重健一郎
    • Organizer
      第52回日本婦人科腫瘍学会学術講演会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] 卵巣癌細胞におけるHIFを分子標的とした阻害剤の作用メカニズム2012

    • Author(s)
      鈴木 紀子
    • Organizer
      第11回日本婦人科がん分子標的研究会
    • Place of Presentation
      茨城県日光市
    • Related Report
      2012 Research-status Report
  • [Presentation] 卵巣癌におけるHIF-1 阻害剤によるcancer stem cell-like cellの増大抑制効果に関する検討2012

    • Author(s)
      鈴木 紀子
    • Organizer
      第71回 日本癌学会学術総会
    • Place of Presentation
      北海道札幌市
    • Related Report
      2012 Research-status Report
  • [Presentation] 卵巣癌におけるHIF阻害剤の癌幹細胞化抑制効果の検討2012

    • Author(s)
      鈴木 紀子
    • Organizer
      第10回 がんとハイポキシア研究会
    • Place of Presentation
      神奈川県横浜市
    • Related Report
      2012 Research-status Report
  • [Presentation] Lengyel E, Kimura T : Identification of microRNA which regulates peritoneal dissemination of ovarian cancer2011

    • Author(s)
      Ohyagi C, Sawada K, Morishige K-I
    • Organizer
      American Association for Cancer Research 102nd Annual Meeting 2011
    • Place of Presentation
      Orlando, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] HIF-1を分子標的とした阻害剤の 卵巣癌治療薬としての可能性2011

    • Author(s)
      鈴木 紀子
    • Organizer
      第10回日本婦人科がん分子標的研究会
    • Place of Presentation
      島根県松江市
    • Related Report
      2011 Research-status Report
  • [Presentation] HIF-1 targeting inhibit tumor angiogenesis in ovarian cancer2011

    • Author(s)
      鈴木 紀子
    • Organizer
      第70回 日本癌学会学術総会
    • Place of Presentation
      愛知県名古屋市
    • Related Report
      2011 Research-status Report
  • [Presentation] HIF-1阻害剤の卵巣癌治療薬としての可能性2011

    • Author(s)
      鈴木 紀子
    • Organizer
      第9回 がんとハイポキシア研究会
    • Place of Presentation
      東京都豊島区
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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