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New oligonucleotide therapeutics using polymeric nano-micelles conjugated with tumor suppressive microRNA in bladder cancer

Research Project

Project/Area Number 18K09198
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionKagoshima University

Principal Investigator

YAMADA Yasutoshi  鹿児島大学, 医歯学域医学系, 講師 (40437968)

Co-Investigator(Kenkyū-buntansha) 榎田 英樹  鹿児島大学, 医歯学域医学系, 准教授 (80347103)
吉野 裕史  鹿児島大学, 医歯学域医学系, 助教 (90642611)
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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords膀胱癌 / microRNA / ナノミセル / ドラッグデリバリー / miR-218 / miR-1 / マイクロRNA / 核酸医薬 / 高分子ナノミセル
Outline of Final Research Achievements

We synthesized chimeric double strand microRNA (miR) containing nucleotide sequence of tumor suppressive miR-218. When miR-218 conjugated with unit PIC administrated to bladder cancer (BC) cell lines, the intra-cellular concentration of miR-218 increased more than one hundred time compared to before administration. Apoptosis was induced in the treated cells by the MagicRed analysis. Next, administrating the exosome with high expression of tumor suppressive miR-1 to BC cells repressed cell proliferation, migration and invasion compared to the controls. In vivo study showed that the xenograft size was significantly reduced in the mice with injection of the miR-1 exosome compared to the controls.

Academic Significance and Societal Importance of the Research Achievements

一連の研究により、癌抑制型マイクロRNAをin vitroあるいはin vivoで投与する新規マイクロRNA投与手段を開発できた。さらに抗腫瘍効果を確認できた。最適化のためさらなる条件の検討が必要ではあるが、これまでin vitroでリポフェクタミン法によるトランスフェクションしか導入手段がなかったため、今後、癌抑制型マイクロRNAの臨床応用の可能性を拓くことが出来たことは学術的意義が大きい。実臨床で治療手段の少ない膀胱癌患者にとって福音となり得る。

Report

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

    (6 results)

All 2021 2020 2019 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (2 results) Remarks (1 results)

  • [Journal Article] EHHADH contributes to cisplatin resistance through regulation by tumor-suppressive microRNAs in bladder cancer2021

    • Author(s)
      Okamura Shunsuke、Yoshino Hirofumi、Kuroshima Kazuki、Tsuruda Masafumi、Osako Yoichi、Sakaguchi Takashi、Yonemori Masaya、Yamada Yasutoshi、Tatarano Shuichi、Nakagawa Masayuki、Enokida Hideki
    • Journal Title

      BMC Cancer

      Volume: 21 Issue: 1 Pages: 48-48

    • DOI

      10.1186/s12885-020-07717-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oncogenic effects of RAB27B through exosome independent function in renal cell carcinoma including sunitinib-resistant2020

    • Author(s)
      Tsuruda Masafumi、Yoshino Hirofumi、Okamura Shunsuke、Kuroshima Kazuki、Osako Yoichi、Sakaguchi Takashi、Sugita Satoshi、Tatarano Shuichi、Nakagawa Masayuki、Enokida Hideki
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 5 Pages: e0232545-e0232545

    • DOI

      10.1371/journal.pone.0232545

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of PHGDH expression in bladder cancer: potential targeting therapy with gemcitabine/cisplatin and the contribution of promoter DNA hypomethylation2020

    • Author(s)
      Hirofumi Yoshino, Hideki Enokida, Yoichi Osako, Nijiro Nohata, Masaya Yonemori, Satoshi Sugita, Kazuki Kuroshima, Masafumi Tsuruda, Shuichi Tatarano, Masayuki Nakagawa.
    • Journal Title

      Molecular Oncology

      Volume: 54 Issue: 9 Pages: 2190-2202

    • DOI

      10.1002/1878-0261.12697

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] PHGDHを標的とした新規膀胱癌治療の可能性とその発現機構の解明2021

    • Author(s)
      吉野裕史, 大迫洋一, 鶴田雅史, 黒島和樹, 岡村俊介, 榎田英樹, 中川昌之.
    • Organizer
      第30回泌尿器科分子・細胞研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 膀胱癌に対するナノミセル型薬物搬送システムを介した癌抑制型マイクロRNAによる新規核酸治療の開発2019

    • Author(s)
      榎田英樹
    • Organizer
      107回 日本泌尿器科学会総会
    • Related Report
      2018 Research-status Report
  • [Remarks] 鹿児島大学大学院医歯学総合研究科 腫瘍学講座泌尿器科学分野

    • URL

      http://www.kufm.kagoshima-u.ac.jp/~urology/

    • Related Report
      2019 Research-status Report

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

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