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Why is the treatment of peritoneal dissemination so difficult? Analyses focusing on microRNA and exosome.

Research Project

Project/Area Number 26293360
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

Sawada Kenjiro  大阪大学, 医学(系)研究科(研究院), 講師 (00452392)

Co-Investigator(Kenkyū-buntansha) 馬淵 誠士  大阪大学, 医学(系)研究科(研究院), 助教 (00452441)
木村 正  大阪大学, 医学(系)研究科(研究院), 教授 (90240845)
橋本 香映  大阪大学, 医学(系)研究科(研究院), 助教 (90612078)
磯部 晶  大阪大学, 医学(系)研究科(研究院), 助教 (60397619)
Research Collaborator Kinose Yasuto  
Nakamura Koji  
Yoshimura Akihiko  
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
KeywordsOvarian cancer / peritoneal dissemination / microRNA / exosome / paclitaxel / 卵巣癌 / マイクロRNA / CD44 miR-99a / バイオマーカー / 腹膜播種 / 卵巣がん / エクソソーム / パクリタキセル耐性 / 低酸素刺激
Outline of Final Research Achievements

The overcome of paclitaxel resistance is a critical issue in ovarian cancer treatment. We aimed to identify key miRNAs which regulate paclitaxel resistance and to pursue those potential as therapeutic targets. Two paclitaxel resistant ovarian cancer cell lines were established by a continuous exposure. MiRNA PCR arrays were performed and miR-194 was found to be one of down-regulated miRNAs. We found that miR-194 acts as a tumor suppressor miRNA through the sensitization to paclitaxel and can be considered as a therapeutic target for paclitaxel-resistant ovarian cancer. Further, we aimed to identify the functional roles of ovarian cancer-derived exosomes during peritoneal dissemination. Exosomes were isolated from ovarian cancer cell lines. Ovarian cancer invasion was significantly promoted in the presence of exosome-treated human peritoneal mesothelial cells (HPMCs). We proved that ovarian cancer-derived exosomes transfer CD-44 to HPMCs, which can facilitate ovarian cancer invasion.

Report

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

    (32 results)

All 2017 2016 2015 2014

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 9 results,  Acknowledgement Compliant: 2 results) Presentation (23 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Exosomes Promote Ovarian Cancer Cell Invasion through Transfer of CD44 to Peritoneal Mesothelial Cells.2017

    • Author(s)
      Nakamura, K. Sawada, K. Kinose, Y. Yoshimura, A. Toda, A. Nakatsuka, E. Hashimoto, K. Mabuchi, S. Morishige, KI. Kurachi, H. Lengyel, E. Kimura, T.
    • Journal Title

      Mol Cancer Res

      Volume: 15(1) Issue: 1 Pages: 78-92

    • DOI

      10.1158/1541-7786.mcr-16-0191

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Clinical relevance of circulating cell-free microRNAs in ovarian cancer.2016

    • Author(s)
      Nakamura, K. Sawada, K. Yoshimura, A. Kinose, Y. Nakatsuka, E. Kimura, T.
    • Journal Title

      Mol Cancer

      Volume: 24;15(1) Issue: 1 Pages: 48-48

    • DOI

      10.1186/s12943-016-0536-0

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The Novel IκB Kinase β Inhibitor, IMD-0560, Has Potent Therapeutic Efficacy in Ovarian Cancer Xenograft ModelMice.2016

    • Author(s)
      Sawada, I. Hashimoto, K. Sawada, K. Kinose, Y. Nakamura, K. Toda, A. Nakatsuka, E. Yoshimura, A. Mabuchi, S. Fujikawa, T. Itai, A. Kimura, T.
    • Journal Title

      Int J Gynecol Cancer

      Volume: 26(4) Issue: 4 Pages: 610-618

    • DOI

      10.1097/igc.0000000000000668

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeting Inhibitor of κB Kinase β Prevents Inflammation-Induced Preterm Delivery by Inhibiting IL-6 Production from Amniotic Cells.2016

    • Author(s)
      Toda, A. Sawada, K. Fujikawa, T. Wakabayashi, A. Nakamura, K. Sawada, I. Yoshimura, A. Nakatsuka, E. Kinose, Y. Hashimoto, K. Mabuchi, S. Tokuhira, A. Nakayama, M. Itai, A. Kurachi, H. Kimura, T.
    • Journal Title

      Am J Pathol

      Volume: 186(3) Pages: 616-629

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Is the exosome a potential target for cancer immunotherapy?2016

    • Author(s)
      Yoshimura, A. Sawada, K. Kimura, T.
    • Journal Title

      Ann Transl Med

      Volume: 5(5) Issue: 5 Pages: 117-117

    • DOI

      10.21037/atm.2017.01.47

    • Related Report
      2016 Annual Research 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 trial.2015

    • 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 Issue: 2 Pages: 288-295

    • DOI

      10.1097/igc.0000000000000333

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The hypoxia-related microRNA miR-199a-3p displays tumor suppressor functions in ovarian carcinoma2015

    • Author(s)
      Kinose, Y. Sawada, K. Nakamura, K. Sawada, I. Toda, A. Nakatsuka, E. Hashimoto, K. Mabuchi, S. Takahashi, K. Kurachi, H. Lengyel, E. Kimura, T.
    • Journal Title

      Oncotarget

      Volume: -

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interleukin 6 receptor is an independent prognostic factor and a potential therapeutic target of ovarian cancer.2015

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

      PloS One

      Volume: 10 Issue: 2 Pages: e0118080-e0118080

    • DOI

      10.1371/journal.pone.0118080

    • Related Report
      2014 Annual Research 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
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 婦人科癌治療に伴う骨粗鬆症に対する介入試験 - デノスマブとリセドロネートの治療効果の比較検討2016

    • Author(s)
      中塚えりか 澤田健二郎 木瀬康人 吉村明彦 黒田浩正 小笹勝巳 中村幸司 馬淵誠士 木村正
    • Organizer
      第31回日本女性医学学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2016-11-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] 婦人科悪性腫瘍治療後の卵巣機能喪失により生じる不定愁訴に対する漢方薬治療の可能性の検討2016

    • Author(s)
      吉村明彦 澤田健二郎 笹野智之 小笹勝巳 黒田浩正 中塚えりか 中村幸司 木瀬康人 木村正
    • Organizer
      第31回日本女性医学学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2016-11-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] 婦人科癌治療に伴う骨粗鬆症に対するデノスマブの有用性の検討2016

    • Author(s)
      中塚えりか 澤田健二郎 木瀬康人 吉村明彦 黒田浩正小笹勝巳 小玉美智子 橋本香映 中村幸司 馬淵誠士 木村正
    • Organizer
      第135回近畿産婦人科学会
    • Place of Presentation
      京都
    • Year and Date
      2016-10-22
    • Related Report
      2016 Annual Research Report
  • [Presentation] Elevated level of serum miR-99a is correlated with serous epithelial ovarian cancer and can be a potential biomarker.2016

    • Author(s)
      Yoshimura, A. Sawada, K. Nakamura, K. Kinose, Y. Nakatsuka, E. Mabuchi, S. Kimura, T.
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Analysis of PAI-1 (plasmin activator inhibitor 1) as a potential therapeutic target for ovarian cancer.2016

    • Author(s)
      Nakatsuka, E. Sawada, K. Nakamura, K. Yoshimura, A. Kinose, Y. Mabuchi, S. Itai, A. Kimura, T.
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Elevated level of circulating microRNA-99a correlates with serous epithelial ovarian cancer and can be used as a potential biomarker.2016

    • Author(s)
      Yoshimura, A. Sawada, K. Nakamura, K. Kinose, Y. Nakatsuka, E. Mabuchi, S. Kimura, T.
    • Organizer
      第68回日本産科婦人科学会学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] PAI-1(plasmin activator inhibitor 1)as a therapeutic target for ovarian cancer.2016

    • Author(s)
      Nakatsuka, E. Sawada, K. Nakamura, K. Yoshimura, A. Makino, H. Sawada, I. Toda, A. Mabuchi, S. Morishige, K. Kimura, T.
    • Organizer
      第68回日本産科婦人科学会学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] Elevated level of circulating microRNA-99a is correlated with serous epithelial ovarian cancer and can be used as a potential biomarker.2016

    • Author(s)
      Yoshimura, A. Sawada, K. Nakamura, K. Kinose, Y. Nakatsuka, E. Mabuchi, S. Kimura, T.
    • Organizer
      AACR Annual Meeting 2016
    • Place of Presentation
      New Orleans, Louisiana, USA
    • Year and Date
      2016-04-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Ovarian cancer cells promote cancer invasion by transferring CD44 to mesothelial cells via exosomes.2015

    • Author(s)
      Koji Nakamura, Kenjiro Sawada, Yasuto Kinose, Erika Nakatsuka, Akihiko Yoshimura, Seiji Mabuchi, Tadashi Kimura
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 卵巣がんにおける PAI-1 (プラスミノーゲン活性化抑制因子 1)の 発現の解析及び新規阻害剤の治療応用への可能性の検討2015

    • Author(s)
      中塚 えりか、澤田 健二郎、中村 幸司、吉村 明彦、木瀬 康人、馬淵 誠士、木村 正
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Ovarian cancer exosomes promote invasion by affecting mesothelial cells through the upregulation of MMP9 secretion and mesothelial cell barrier.2015

    • Author(s)
      Koji Nakamura, Kenjiro Sawada, Yasuto Kinose, Akihiko Yoshimura, Erika Nakatsuka, Seiji Mabuchi, Tadashi Kimura
    • Organizer
      第57回日本婦人科腫瘍学会学術講演会
    • Place of Presentation
      盛岡
    • Year and Date
      2015-08-07
    • Related Report
      2015 Annual Research Report
  • [Presentation] Exosome transfer from ovarian cancer cells to mesothelial cells promotes cell invasion by upregulating MMP-9 secretion and increasing clearance of mesothelial cells.2015

    • Author(s)
      Koji Nakamura, Kenjiro Sawada, Yasuto Kinose, Akihiko Yoshimura, Erika Nakatsuka, Seiji Mabuchi, Tadashi Kimura.
    • Organizer
      American Association for Cancer Research Annual Meeting 2015
    • Place of Presentation
      America, Pennsylvania
    • Year and Date
      2015-04-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 卵巣癌細胞由来exosome の腹膜中皮細胞への情報伝達機構の解明―癌細胞由来CD44 はexosome により中皮細胞に移行し,腹膜中皮のMMP 9 分泌促進,Ecadherin 発現抑制を誘導し腹膜播種を促進する2015

    • Author(s)
      中村幸司 澤田健二郎 木瀬康人 吉村明彦 中塚えりか 戸田有朱香 橋本香映 馬淵誠士 木村正
    • Organizer
      第67回日本産科婦人科学会学術講演会
    • Place of Presentation
      横浜
    • Year and Date
      2015-04-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 卵巣がんにおけるPAI 1(プラスミノーゲン活性化抑制因子1)の発現の検討とその阻害剤の抗がん治療への可能性の検討2015

    • Author(s)
      中塚えりか 澤田健二郎 中村幸司 吉村明彦 木瀬康人 澤田育子 戸田有朱香 馬淵誠士 木村正
    • Organizer
      第67回日本産科婦人科学会学術講演会
    • Place of Presentation
      横浜
    • Year and Date
      2015-04-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 婦人科癌治療後により生じる骨密度低下に対するリセドロン酸ナトリウム水和物(リセドロネート)の有用性の検討2014

    • Author(s)
      木瀬康人. 澤田健二郎. 戸田有朱香. 笹野智之. 澤田育子. 松本有里. 坂田正博. 木村 正
    • Organizer
      第29回日本女性医学学会
    • Place of Presentation
      東京
    • Year and Date
      2014-11-01 – 2014-11-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] 大阪大学における前置胎盤、前置癒着胎盤手術の治療成績と工夫2014

    • Author(s)
      木瀬康人. 小笹勝巳. 松崎慎哉. 金川武司. 澤田健二郎. 木村 正
    • Organizer
      第37回日本産婦人科手術学会
    • Place of Presentation
      札幌
    • Year and Date
      2014-10-11 – 2014-10-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 低酸素関連 microRNA、miR-199a-3p は c-Met の発現抑制により卵巣癌腹膜播種の進展を抑制する2014

    • Author(s)
      木瀬康人. 澤田健二郎. 馬淵誠士. 木村 正
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 卵巣癌においてmiR-194はBMI-1を制御することでパクリタキセル耐性を減弱させる2014

    • Author(s)
      中村幸司. 澤田健二郎. 木瀬康人. 橋本香映. 木村 正
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] The effect of raloxifene hydrochloride for the prevention of health care problems of patients who underwent surgeries for endometrial cancer: A multicenter clinical trial2014

    • Author(s)
      Nakamura, K. Sawada, K. Sugiyama, M. Mabuchi, S. Hisamatsu, T. Nishio, Y. Ito, K. Kimura, T. Kamiura, S. Morishige, K.
    • Organizer
      50th Annual Meeting of the American Society of Clinical Oncology
    • Place of Presentation
      Chicago, U.S.A.
    • Year and Date
      2014-05-30 – 2014-06-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] 子宮体癌術後のヘルスケアに関する多施設共同非盲検ランダム化比較試験-ラロキシフェンは骨密度を上昇させ、コレステロール値を低下させる2014

    • Author(s)
      中村幸司. 澤田健二郎. 杉山三知代. 馬淵誠士. 久松武志. 西尾幸浩. 伊藤公彦. 森重健一郎. 木村 正. 上浦祥司
    • Organizer
      第66回日本産科婦人科学会
    • Place of Presentation
      東京
    • Year and Date
      2014-04-18 – 2014-04-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 低酸素環境下で発現が変動する microRNA の網羅的解析を通じた卵巣癌腹膜播種抑制の分子標的治療の可能性-低酸素刺激で発現低下を示すmiR-199a-3pはc-Metの発現抑制を通じて播種進展を抑制する2014

    • Author(s)
      木瀬康人. 澤田健二郎. 中村幸司. 牧野 弘. 水野智子. 橋本香映. 磯部 晶. 馬淵誠士. 坂田正博. 森重健一郎. 木村 正
    • Organizer
      第66回日本産科婦人科学会
    • Place of Presentation
      東京
    • Year and Date
      2014-04-18 – 2014-04-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Hypoxia related microRNA, miR-199a-3p, inhibits ovarian cancer progression through the suppression of c-Met expression2014

    • Author(s)
      Kinose, Y. Sawada, K. Nakamura, K. Mabuchi, S. Morishige, K. Kimura, T.
    • Organizer
      105th Annual Meeting of the American Association for Cancer Research
    • Place of Presentation
      San Diego, U.S.A.
    • Year and Date
      2014-04-05 – 2014-04-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Identification of microRNA which regulates paclitaxel resistance of ovarian cancer cells - a potential of miR-194 by attenuating paclitaxel resistance through the down-regulation of oncogene BMI-12014

    • Author(s)
      Nakamura, K. Sawada, K. Kinose, Y. Hashimoto, K. Mabuchi, S. Kimura, T.
    • Organizer
      105th Annual Meeting of the American Association for Cancer Research
    • Place of Presentation
      San Diego, U.S.A.
    • Year and Date
      2014-04-05 – 2014-04-09
    • Related Report
      2014 Annual Research Report

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

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