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Identification of cancer stem-like cells of ovarian clear cell carcinoma and analysis of its chemotherapy-resistance mechanism

Research Project

Project/Area Number 26462519
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, 大学院医学系研究科, 教授 (90283788)

Co-Investigator(Kenkyū-buntansha) 古井 辰郎  岐阜大学, 大学院医学系研究科, 准教授 (00313883)
牧野 弘  岐阜大学, 医学部附属病院, 助教 (20649107)
鈴木 紀子  岐阜大学, 大学院医学系研究科, 学術研究補佐員 (40642096)
水野 智子  岐阜大学, 医学部附属病院, 医員 (60444262)
川島 英理子 (佐藤英理子 / 川島 英理子(佐藤英理子))  岐阜大学, 医学部附属病院, 助教 (80444264)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords卵巣癌 / 癌幹細胞 / 明細胞癌 / 卵巣がん / 明細胞腺癌 / 活性酵素 / 活性酸素
Outline of Final Research Achievements

We investigated the relationship between a CSC marker, aldehyde dehydrogenase1 (ALDH1), and clinical prognosis using ovarian clear cell carcinoma tissue samples. As a result, high ALDH1 expression levels are related to advanced stage in clear cell carcinoma cases. ALDH1 expression significantly reduced progression free survival. Furthermore, we investigated the antioxidant mechanism by which CSCs maintain a lower reactive oxygen species (ROS) level, which provides protection from chemotherapeutic agents. In vitro study revealed that ALDH-high cells contained a lower ROS level than ALDH-low cells. Antioxidant enzymes were upregulated in ALDH-high cells. ALDH-high cells showed increased expression of Nrf2, a key transcriptional factor of the antioxidant system.
In conclusion, ALDH-positive CSCs might have increased Nrf2-induced antioxidant scavengers, which lower ROS level relevant to chemoresistance in ovarian clear cell carcinoma.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (15 results)

All 2016 2015 2014

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 10 results,  Acknowledgement Compliant: 5 results) Presentation (2 results)

  • [Journal Article] : A retrospective study of the treatments and prognosis of bone metastasis from cervical cancer (KCOG-G1202s)2016

    • Author(s)
      1.Makino H, Nishio S, Tsubamoto H, Shimada M, Nishikawa R, Kai K, Ito K, Mizuno T, Ushijima K, Morishige K-I
    • Journal Title

      The Journal of Obstetrics and Gynaecology Research

      Volume: 42 Issue: 6 Pages: 701-706

    • DOI

      10.1111/jog.12956

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Creating a Global Community of Practice for Oncofertility.2016

    • Author(s)
      Lauren M. Ataman, Jhenifer K. Rodrigues, Ricardo M. Marinho, João P.J. Caetano, aurício B. Chehin, Eduardo L. Alves da, Motta, Paulo Serafini, Suzuki N, Furui T, Takae S, Sugishita Y, Morishige K-I, Telfer, Satish K. Adiga
    • Journal Title

      Journal of Global Oncology

      Volume: 2 Issue: 2 Pages: 83-96

    • DOI

      10.1007/s12522-015-0219-3

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Clear cell carcinoma of the ovary: comparison of MR findings of histological subtypes2016

    • Author(s)
      5.Kato H, Hatano Y, Makino H, Furui T, Morishige K-I, Matsuo M
    • Journal Title

      Abdom Radiol

      Volume: 41 Issue: 12 Pages: 2476-2483

    • DOI

      10.1007/s00261-016-0777-9

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 低酸素をターゲットとした卵巣癌治療薬の展望2015

    • Author(s)
      鈴木紀子、永澤秀子、水野智子、森重健一郎
    • Journal Title

      産科と婦人科

      Volume: 82 Pages: 1106-1111

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cancer stem-like cells of ovarian clear cell carcinoma are enriched in the ALDH-high population associated with an accelerated scavenging system in reactive oxygen species2015

    • Author(s)
      Mizuno T, Suzuki N, Makino H, Furui T, Morii E, Aoki H, Kunisada T, Morishige K
    • Journal Title

      Gynecologic Oncology

      Volume: 137 Pages: 299-305

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The inhibitory effect of hypoxic cytotoxin on the expansion of cancer stem cells in ovarian cancer2015

    • Author(s)
      Noriko Nozawa-Suzukia, Hideko Nagasawab, Ken Ohnishic, Ken-ichirou Morishigea
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 457 Issue: 4 Pages: 706-711

    • DOI

      10.1016/j.bbrc.2015.01.053

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] IKKβ Regulates VEGF Expression and Is a Potential Therapeutic Target for Ovarian Cancer as an Anti-angiogenic Treatment2015

    • Author(s)
      Kinose, Y. Sawada, K. Makino, H. Ogura, T. Mizuno, T. Suzuki, N. Fujikawa, T. Morii, E. Nakamura, K. Sawada, I. Toda, A. Hashimoto, K. Isobe, A. Mabuchi, S. Ohta, T. Itai, A. Morishige, K. I. Kurachi, H. Kimura, T
    • Journal Title

      Mol Cancer Ther

      Volume: 14 Issue: 4 Pages: 909-19

    • DOI

      10.1158/1535-7163.mct-14-0696

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy of raloxifene hydrochloride for the prevention of health care problems in patients who undergo surgery for endometrial cancer: a multicenter randomized clinical trial2015

    • Author(s)
      Nakamura K, Sawada K, Sugiyama M, Mabuchi S, Hisamatsu T, Nishio Y, Ito K, Kimura T, Kamiura S, Morishige K
    • Journal Title

      Int J Gynecol Cancer

      Volume: 25 Pages: 288-295

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Exploratory study of pre-surgical medications with dienogest or leuprorelin in laparoscopic cystectomy of endometrial cysts2015

    • Author(s)
      Takenaka M, Yano R, Hiraku Y, Shibata M, Hatano K, Yamamoto S, Sato K, Yamamoto K, Morishige KI
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 41 Issue: 8 Pages: 1234-1239

    • DOI

      10.1111/jog.12701

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assessment of uterine enhancement rate after abdominal radical trachelectomy using dynamic contrast-enhanced magnetic resonance imaging2015

    • Author(s)
      Makino H, Furui T, Hayasaki Y, Morishige K-I
    • Journal Title

      Archives of Gynecology and Obstetrics

      Volume: - Issue: 3 Pages: 625-632

    • DOI

      10.1007/s00404-015-3842-7

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation by heat shock protein 22 (HSPB8) of transforming growth factor-α-induced ovary cancer cell migration.2015

    • Author(s)
      Suzuki M, Matsushima-Nishiwaki R, Kuroyanagi G, Suzuki N, Takamatsu R, Furui T, Yoshimi N, Kozawa O, Morishige K.
    • Journal Title

      Arch Biochem Biophys.

      Volume: 571 Pages: 40-49

    • DOI

      10.1016/j.abb.2015.02.030

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Prenatal MR imaging diagnosis of placental invasion.2014

    • Author(s)
      Noda Y, Kanematsu M, Goshima S, Kondo H, Watanabe H, Kawada H, Kawai N, Tanahashi Y, Furui T, Morishige K, Kyongtae T. Bae
    • Journal Title

      Abdom Imaging

      Volume: -

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cancer stem-like cells of ovarian clear cell carcinoma are enriched in the ALDH-high population associated with an accelerated scavenging system in reactive oxygen species2014

    • Author(s)
      Mizuno T, Suzuki N, Makino H, Furui T, Morii E, Aoki H, Kunisada T, Morishige K
    • Journal Title

      Gynecologic Oncology

      Volume: - Issue: 2 Pages: 299-305

    • DOI

      10.1016/j.ygyno.2014.12.005

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 低酸素の視点からみた卵巣内膜症嚢胞における鉄動態2016

    • Author(s)
      竹中基記、鈴木紀子、森美奈子、平山祐、永澤秀子、森重健一郎
    • Organizer
      第14回がんとハイポキシア研究会
    • Place of Presentation
      岐阜グランドホテル
    • Year and Date
      2016-11-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] 子宮頸癌におけるCD44vとxCTの発現と役割2016

    • Author(s)
      森美奈子、竹中基記、牧野弘、古井辰郎、森重健一郎
    • Organizer
      第68回日本産科婦人科学会学術講会
    • Place of Presentation
      東京フォーラム
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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