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The development of a novel microRNA replacement therapy for ovarian cancer - a potential of patient derived-exosomes as a carrier.

Research Project

Project/Area Number 18K09227
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionOsaka University

Principal Investigator

Sawada Kenjiro  大阪大学, 医学系研究科, 講師 (00452392)

Co-Investigator(Kenkyū-buntansha) 馬淵 誠士  奈良県立医科大学, 医学部, 講師 (00452441)
小玉 美智子  大阪大学, 医学系研究科, 助教 (70791391)
木村 正  大阪大学, 医学系研究科, 教授 (90240845)
橋本 香映  大阪大学, 医学部附属病院, 特任准教授(常勤) (90612078)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords卵巣癌 / マイクロRNA / エクソソーム / バイオマーカー / DDS / 腹膜播種 / miR-99a-5p / miR-1290
Outline of Final Research Achievements

MicroRNAs (miRNAs) affect key features of cancer cells. Exosomes are stable in body fluid and therefore can serve as a promising candidate for miRNA carrier. In ovarian cancer treatment, omentum should be taken at surgery and normal fibroblasts can be collected from omentum. The aim of this study is to pursue the possibility of fibroblast derived-exosomes as a carrier for miRNA replacement therapy. At surgery, omentum was collected and fibroblasts were primary cultured. Thereafter, exosomes were collected from culture media. Synthesized miR-199a-3p was corporated into exosomes by electroporation. The treatment of miR-199a-3p-loaded exosomes (M199-exosomes) was assessed. The treatment of M199-exosomes drastically increased miR-199a-3p expression followed by c-Met down-regulation and significantly inhibited the proliferation and invasion of ovarian cancer cells in vitro and in vivo. As a conclusion, exosomes derived from patients’ fibroblasts can serve as superior carrier of miRNA.

Academic Significance and Societal Importance of the Research Achievements

卵巣癌患者大網由来のエクソソームを核酸試薬のキャリアとして用いた場合、卵巣がん細胞への選択性と効率の高い核酸の取り込みが期待でき、治療効果が期待できることを証明した。今後の新規の核酸治療への応用の可能性を提示した。腹膜播種は腹膜癌や婦人科癌に留まらず、胃癌や大腸癌などの消化器癌においても、極めて難治で、治癒はほぼ不可能である。今回の研究成果は、消化器癌などにおける腹膜播種形成にも応用できると考えており、新規の癌治療として臨床応用できる可能性を有している。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2021 2020 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (4 results)

  • [Journal Article] Exploring the potential of engineered exosomes as delivery systems for tumor-suppressor microRNA replacement therapy in ovarian cancer2020

    • Author(s)
      Kobayashi Masaki、Sawada Kenjiro、Miyamoto Mayuko、Shimizu Aasa、Yamamoto Misa、Kinose Yasuto、Nakamura Koji、Kawano Mahiru、Kodama Michiko、Hashimoto Kae、Kimura Tadashi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 527 Issue: 1 Pages: 153-161

    • DOI

      10.1016/j.bbrc.2020.04.076

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exosomal miR-1290 is a potential biomarker of high-grade serous ovarian carcinoma and can discriminate patients from those with malignancies of other histological types2018

    • Author(s)
      Kobayashi Masaki、Sawada Kenjiro、Nakamura Koji、Yoshimura Akihiko、Miyamoto Mayuko、Shimizu Aasa、Ishida Kyoso、Nakatsuka Erika、Kodama Michiko、Hashimoto Kae、Mabuchi Seiji、Kimura Tadashi
    • Journal Title

      Journal of Ovarian Research

      Volume: 11 Issue: 1 Pages: 81-81

    • DOI

      10.1186/s13048-018-0458-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exosomal miR-99a-5p is elevated in sera of ovarian cancer patients and promotes cancer cell invasion by increasing fibronectin and vitronectin expression in neighboring peritoneal mesothelial cells2018

    • Author(s)
      Yoshimura Akihiko、Sawada Kenjiro、Nakamura Koji、Kinose Yasuto、Nakatsuka Erika、Kobayashi Masaki、Miyamoto Mayuko、Ishida Kyoso、Matsumoto Yuri、Kodama Michiko、Hashimoto Kae、Mabuchi Seiji、Kimura Tadashi
    • Journal Title

      BMC Cancer

      Volume: 18 Issue: 1 Pages: 1065-1065

    • DOI

      10.1186/s12885-018-4974-5

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Patient-derived Exosomes Can Work as a Carrier of siRNA Delivery for the Treat- ment of Ovarian Cancer Peritoneal Dissemination.2021

    • Author(s)
      Shimizu, A. Sawada, K. Kobayashi, M. Yamamoto, M. Yagi, T. Kimura, T.
    • Organizer
      第62回日本婦人科腫瘍学会学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Excellent Usefulness of Engineered Exosomes as a Carrier for Tumor-suppressor microRNA Replacement Therapy of Ovarian Cancer2021

    • Author(s)
      kobayashi, M. Sawada, K. Miyamoto, M. Shimizu, A. Yamamoto, M. Kawano, M. Kodama, M. Hashimoto, K. Kimura, T.
    • Organizer
      第62回日本婦人科腫瘍学会学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Potential of patient-derived exosomes as a carrier of siRNA delivery for the treatment of ovarian cancer peritoneal dissemination2020

    • Author(s)
      Shimizu, A. Sawada, K. Kobayashi, M. Miyamoto, M. Kinose, Y. Kodama, M. Hashimoto, K. Kimura, T.
    • Organizer
      第72回日本産科婦人科学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] The potential of engineered exosomes as a carrier of tumor-suppressor microRNA replacement therapy for ovarian cancer2020

    • Author(s)
      Kobayashi, M. Sawada, K. Miyamoto, M. Shimizu, A. Yamamoto, M. Kawano, M. Kodama, M. Hashimoto, K. Kimura, T.
    • Organizer
      第72回日本産科婦人科学会
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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