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The therapeutic strategy toward overcoming drug resistance of gynecologic cancers utilizing high throughput screening.

Research Project

Project/Area Number 24390375
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionTohoku University

Principal Investigator

YAEGASHI Nobuo  東北大学, 医学(系)研究科(研究院), 教授 (00241597)

Co-Investigator(Kenkyū-buntansha) TOYOSHIMA Masafumi  東北大学, 大学院医学系研究科, 非常勤講師 (70451581)
Co-Investigator(Renkei-kenkyūsha) NAGASE Satoru  山形大学, 医学部, 教授 (00292326)
SUZUKI Fumihiko  東北大学, 大学院医学系研究科, 助教 (20400343)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2014: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Keywordsスクリーニング / 薬剤耐性 / 婦人科がん / 化学療法 / シスプラチン
Outline of Final Research Achievements

The purpose of this study is to search the molecules that can cancel the cisplatin resistance of cancer cells. We explore the molecules that show a synthetic lethal effect with a small amount of CDDP administration in a high-throughput screening using siRNA library consisting of 6650 genes. As a result, a strong expression of TIE-1 was found to be decrease the sensitivity toward cisplatin in several ovarian cancer cell lines. The relationship among TIE-1, ovarian cancer and/or drug resistance has not been reported. In order to examine the significance of TIE-1 expression in ovarian cancer patients, in silico analysis was carried out. We confirmed that TIE-1 high expression group has a significantly poor prognosis by examination of the overall survival in 1582 ovarian cancer patients. Furthermore, we confirmed that apoptosis and γH2AX expressions, a marker for DNA-double strand breaks, were significantly decreased during CDDP administration in TIE-1 over-expressed cells.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (25 results)

All 2015 2014 2013 2012 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Acknowledgement Compliant: 1 results,  Open Access: 2 results) Presentation (13 results) (of which Invited: 1 results)

  • [Journal Article] Inhibition of plasminogen activator inhibitor-1 is a potential therapeutic strategy in ovarian cancer.2015

    • Author(s)
      Mashiko S, Kitatani K, Toyoshima M, Ichimura A, Dan T, Usui T, Ishibashi M, Shigeta S, Nagase S, Miyata T, Yaegashi N
    • Journal Title

      Cancer Biology & Therapy

      Volume: 16 Issue: 2 Pages: 253-260

    • DOI

      10.1080/15384047.2014.1001271

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Solitary uterine metastasis of invasive lobular carcinoma after adjuvant endocrine therapy: a case report.2015

    • Author(s)
      Toyoshima M, Iwahashi H, Shima T, Hayasaka A, Kudo T, Makino H, Igeta S, Matsuura R, Ishigaki N, Akagi K, Sakurada J, Suzuki H, Yoshinaga K
    • Journal Title

      Journal of Medical Case Reports

      Volume: 9 Issue: 1 Pages: 47-47

    • DOI

      10.1186/s13256-014-0511-6

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spontaneous retroperitoneal hemorrhage caused by rupture of an ovarian artery aneurysm: a case report and review of the literature.2015

    • Author(s)
      Toyoshima M, Kudo T, Igeta S, Makino H, Momono Y, Shima T, Matsuura R, Ishigaki N, Akagi K,Takeyama Y, Iwahashi H, Rikimaru H, Sato A, Yoshinaga K
    • Journal Title

      Journal of Medical Case Reports

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical outcome of pelvic exenteration in patients with advanced or recurrent uterine cervical cancer.2014

    • Author(s)
      Tanaka S, Nagase S, Kaiho-Sakuma M, Nagai T, Kurosawa H, Toyoshima M, Tokunaga H, Otsuki T, Utsunomiya H, Takano T, Niikura H, Ito K, Yaegashi N.
    • Journal Title

      Int J Clin Oncol

      Volume: 19 Issue: 1 Pages: 133-138

    • DOI

      10.1007/s10147-013-0534-9

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Paclitaxel-carboplatin for advanced or recurrent carcinosarcoma of the uterus: the Japan Uterine Sarcoma Group and Tohoku Gynecologic Cancer Unit Study2014

    • Author(s)
      Tadao Takano,Takeo Otsuki,Hideki Tokunaga,Masafumi Toyoshima,Hiroki Utsunomiya,Satoru Nagase,Hitoshi Niikura,Kiyoshi Ito,Nobuo Yaegashi,Hidekazu Yamada,Toru Tase,Masahiro Kagabu,Tadahiro Shoji,Toru Sugiyama,Naoki Sato,Toshio Fujimoto,Yukihiro Terada, Junzo Kigawa,et al
    • Journal Title

      Int J Clin Oncol.

      Volume: accepted Issue: 6 Pages: 1052-1058

    • DOI

      10.1007/s10147-013-0658-y

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular Pathogenesis of Uterine Serous Carcinoma2014

    • Author(s)
      Satoru Nagase ・ Fumihiko Suzuki ・ Hideki Tokunaga ・Masafumi Toyoshima ・ Hiroki Utsunomiya ・Hitoshi Niikura ・ Nobuo Yaegashi
    • Journal Title

      Curr Obstet Gynecol Rep

      Volume: 3 Issue: 1 Pages: 33-39

    • DOI

      10.1007/s13669-013-0069-0

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of Postoperative Chemotherapy in Patients with Uterine Carcinosarcoma: A Retrospective Survey of the Tohoku Gynecologic Cancer Unit.2014

    • Author(s)
      Otsuki A, Otsuki T, Tokunaga H, Niikura H, Nagase S, Sugiyama T, Toyoshima M, Utsunomiya H, Yokoyama Y, Mizunuma H, Sato N, Terada Y, Shoji T, Sugiyama T, Nakahara K, Ohta T, Yamada H, Tase T, Nishiyama H, Fujimori K, Takano T, Takahashi F, Watanabe Y, Yaegashi N
    • Journal Title

      International Journal of Clinical Oncology

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Outcomes of Abdominal Radical Trachelectomy: Results of a Multicenter Prospective Cohort Study in a Tohoku Gynecologic Cancer Unit.2014

    • Author(s)
      Tokunaga H, Watanabe Y, Niikura H, Nagase S, Toyoshima M, Shiro R, Yoshihito Yokoyama Y, Mizunuma H, Ohta T, Nishiyama H, Watanabe T, Sato N, Sugiyama T, Takano T, Takahashi F, Yaegashi N
    • Journal Title

      International Journal of Clinical Oncology

      Volume: in press Issue: 4 Pages: 776-780

    • DOI

      10.1007/s10147-014-0763-6

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Feasibility study of gemcitabine plus docetaxel in advanced or recurrent uterine leiomyosarcoma and undifferentiated endometrial sarcoma in Japan2013

    • Author(s)
      Takano T, Niikura H, Ito K, Nagase S, Utsunomiya H, Otsuki T, Toyoshima M, Tokunaga H, Kaiho-Sakuma M, Shiga N, Nagai T, Tanaka S, Otsuki A, Kurosawa H, Shigeta S, Yamaguchi T, Yaegashi N.
    • Journal Title

      International Journal of Clinical Oncology.

      Volume: - Issue: 5 Pages: 897-905

    • DOI

      10.1007/s10147-013-0627-5

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Small Cell Carcinoma of the Uterine Cervix: Clinical Outcome of Concurrent Chemoradiotherapy with a Multidrug Regimen2013

    • Author(s)
      Hideki Tokunaga, Satoru Nagase, Kosuke Yoshinaga, Sota Tanaka, Tomyuki Nagai, Hiroki Kurosawa, Michiko Kaiho-Sakuma, Masafumi Toyoshima, et al
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 229 Issue: 1 Pages: 75-81

    • DOI

      10.1620/tjem.229.75

    • NAID

      130004460037

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional Genomics Identifies Therapeutic Targets for MYC-Driven Cancer2012

    • Author(s)
      Masafumi Toyoshima , Heather L Howie , Maki Imakura , Ryan M Walsh , James E Annis , Aaron N. Chang ,et al
    • Journal Title

      PNAS

      Volume: 109 Issue: 24 Pages: 9545-9550

    • DOI

      10.1073/pnas.1121119109

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hysterescopic inspection and total curettage are insufficient fordiscriminating endometrial cancer from atypical endometrial hyperplasia2012

    • Author(s)
      Hiroki Kurosawa, Kiyoshi ito, Hitoshi Nikura, Tadao Takano, Satoru Nagase, Hiroki Ustunomiya, Takeo Otsuki, Masafumi Toyoshima, Tomoyuki Nagai, Souta Tanaka, Mika Watanabe and Nobuo Yaegashi
    • Journal Title

      Tohoku J. Exp. Med.

      Volume: 228 Pages: 365-370

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Transferrin facilitates DNA-double strand breaks via transferrin receptor 1 in human fallopian tube epithelial cells: possible involvement of transferrin in carcinogenesis.2015

    • Author(s)
      Shigeta S, Toyoshima M, Kitatani K, Ishibashi M, Usui T, Yaegashi N
    • Organizer
      Society for Reproductive Investigation 62th scientific annual meeting
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2015-03-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] セラミドによる卵巣がん播種転移制御2015

    • Author(s)
      北谷和之、豊島将文、臼井利典、重田昌吾、石橋ますみ、永瀬智、八重樫伸生
    • Organizer
      第3回婦人科がんバイオマーカー研究会学術集会
    • Place of Presentation
      九州大学医学部百年講堂(福岡市)
    • Year and Date
      2015-02-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] スフィンゴ脂質セラミドを利用した卵巣がん播種転移薬の可能性2014

    • Author(s)
      北谷和之、豊島将文、臼井利典、重田昌吾、石橋ますみ、永瀬智、八重樫伸生
    • Organizer
      第2回婦人科がんバイオマーカー研究会学術集会
    • Place of Presentation
      東京慈恵会医科大学(東京都港区)
    • Year and Date
      2014-07-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] Investigation of PAI-1 as a new therapeutic target for ovarian cancer.2014

    • Author(s)
      Satsuki Mashiko, Masafumi Toyoshima, Kazuyuki Kitatani , Shogo Shigeta , Masumi Ishibashi , Nobuo Yaegashi
    • Organizer
      第66回日本産科婦人科学会学術総会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2014-04-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] セラミドによる細胞運動性の調節:セラミドリポソームの抗卵巣がん播種転移薬としての可能性2014

    • Author(s)
      北谷和之,豊島将文,増子さつき,重田昌吾,石橋ますみ,永瀬智,八重樫伸生
    • Organizer
      第66回日本産科婦人科学会学術総会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2014-04-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 大規模 siRNA スクリーニングを用いた 卵巣がんのシスプラチン抵抗性を克服する分子標的の検討2014

    • Author(s)
      石橋ますみ、豊島将文、北谷和之、増子さつき、重田昌吾、八重樫伸生
    • Organizer
      第66回日本産科婦人科学会学術総会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2014-04-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 大規模siRNAスクリーニングを用いた卵巣がんのシスプラチン抵抗性を克服する分子標的の検討2013

    • Author(s)
      石橋ますみ、豊島将文、北谷和之、増子さつき、重田昌吾、八重樫伸生
    • Organizer
      第1回婦人科がんバイオマーカー研究会学術集会
    • Place of Presentation
      東京大学 伊藤国際学術研究センター
    • Year and Date
      2013-02-16
    • Related Report
      2012 Annual Research Report
  • [Presentation] c-Myc高発現をバイオマーカーとした卵巣がんにおける治療標的分子の同定2013

    • Author(s)
      豊島将文、北谷和之、増子さつき、重出昌吾、石橋ますみ、八重樫伸生
    • Organizer
      第1回婦人科がんバイオマーカー研究会学術集会
    • Place of Presentation
      東京大学 伊藤国際学術研究センター
    • Year and Date
      2013-02-16
    • Related Report
      2012 Annual Research Report
  • [Presentation] Identification of Targeted therapies for Ovarian Cancer by Functional Genomics2012

    • Author(s)
      Masafumi Toyoshima
    • Organizer
      Marsha Rikin the 9th Ovarian Cancer Research Symposium
    • Place of Presentation
      Seattle, USA(招待講演)
    • Year and Date
      2012-09-07
    • Related Report
      2012 Annual Research Report
  • [Presentation] 卵巣がん転移を標的にした創薬:スフィンゴ脂質の利用

    • Author(s)
      北谷和之・豊島将文・増子さつき・重田昌吾・石橋ますみ・八重樫伸生
    • Organizer
      第12回日本婦人科がん分子標的研究会
    • Place of Presentation
      東大寺総合文化センター、奈良市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 卵巣明細胞腺癌におけるPAI-1の発現と血栓症発症の関連についての検討

    • Author(s)
      増子さつき・豊島将文・北谷和之・重田昌吾・八重樫伸生
    • Organizer
      第65回日本産科婦人科学会学術総会
    • Place of Presentation
      札幌市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 卵管上皮内腺癌におけるDNA二本鎖切断とp53発現の免疫組織学的検討

    • Author(s)
      重田昌吾・豊島将文・増子さつき・北谷和之・八重樫伸生
    • Organizer
      第65回日本産科婦人科学会学術総会
    • Place of Presentation
      札幌市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Identification of Targeted Therapies for Ovarian Cancers by Functional Genomics

    • Author(s)
      Masafumi Toyoshima, Kazuyuki Kitatani, Satsuki Mashiko, Shogo Shigeta and Nobuo Yaegashi
    • Organizer
      第65回日本産科婦人科学会学術総会
    • Place of Presentation
      札幌市
    • Related Report
      2013 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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