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The trial to enhance the effect of oncolytic adenovirus

Research Project

Project/Area Number 17K11660
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionHokkaido University

Principal Investigator

Matsuda Aya  北海道大学, 歯学研究院, 特任助教 (60514312)

Co-Investigator(Kenkyū-buntansha) 北村 哲也  北海道大学, 医学研究院, 客員研究員 (00451451)
東野 史裕  北海道大学, 歯学研究院, 准教授 (50301891)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords腫瘍溶解ウイルス / HuR / ARE-mRNA / アデノウイルス / 口腔がん / ARE-mRNA / 抗がん剤 / 癌 / ウイルス
Outline of Final Research Achievements

We developed an oncolytic adenovirus AdΔE4 that can proliferate depending on the nuclear export and stabilization of ARE-mRNA and lyse cancer cells in which ARE-mRNA is stabilized. We investigated whether the effect of AdΔE4 would be enhanced by stimulation of a system that exports ARE-mRNA to the cytoplasm. Therefore, we examined whether stimulation of ARE-mRNA such as anti-cancer drug and ethanol for nuclear export and stabilization would enhance the oncolytic effect of AdΔE4. Under these treatments, the cytoplasmic relocalization of HuR was enhanced, and the effect of AdΔE4 was activated by the combined use with AdΔE4.

Academic Significance and Societal Importance of the Research Achievements

現在まで多くの種類の腫瘍溶解アデノウイルスが開発されたが、ARE-mRNAの輸送・安定化によりその増殖が制限されるウイルスの開発はわれわれ独自の研究である。これまでに外からの刺激を加えることで、腫瘍溶解効果をさらに増強できる腫瘍溶解ウイルスは他に報告されていない。AdΔE4はARE-mRNAの核外輸送・安定化を促進すると考えられる抗がん剤や放射線など他のがん治療法との併用により効果が増強されると考えられ、非常に有用な治療法になると期待できる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (21 results)

All 2020 2019 2018 2017

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (14 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Cisplatin Relocalizes RNA Binding Protein HuR and Enhances the Oncolytic Activity of E4orf6 Deleted Adenovirus2020

    • Author(s)
      Habiba Umma、Hossain Elora、Yanagawa-Matsuda Aya、Chowdhury Abu Faem Mohammad Almas、Tsuda Masumi、Zaman Asad-uz-、Tanaka Shinya、Higashino Fumihiro
    • Journal Title

      Cancers

      Volume: 12 Issue: 4 Pages: 809-809

    • DOI

      10.3390/cancers12040809

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Application of the dredging method in a case of recurrent ameloblastoma that had spread over a large region of the mandible2020

    • Author(s)
      Kakuguchi Wataru、Ohiro Yoichi、Nakazawa Seitaro、Naito Ryo、Moritani Yasuhito、Nakamichi Yoshiyuki、Horimukai Hiromasa、Kitamura Tetsuya、Tei Kanchu
    • Journal Title

      Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology

      Volume: 32 Issue: 1 Pages: 44-48

    • DOI

      10.1016/j.ajoms.2019.09.006

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The neural ELAVL protein HuB enhances endogenous proto-oncogene activation.2019

    • Author(s)
      Hatanaka T, Higashino F, Tei K, Yasuda M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 517(2) Issue: 2 Pages: 38-45

    • DOI

      10.1016/j.bbrc.2019.07.089

    • NAID

      120006886034

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Carbonic anhydrase 2 (CAII) supports tumor blood endothelial cell survival under lactic acidosis in the tumor microenvironment2019

    • Author(s)
      Dorcas Akuba Muhyia Annan, Nako Maishi, Tomoyoshi Soga, Randa Dawood, Cong Li, Hiroshi Kikuchi, Takayuki Hojo, Masahiro Morimoto, Tetsuya Kitamura, Mohammad Towfik Alam, Kazuyuki Minowa, Nobuo Shinohara, Jin-Min Nam, Yasuhiro Hida, Kyoko Hida
    • Journal Title

      Cell Communication and Signaling

      Volume: 17 Issue: 1 Pages: 169-169

    • DOI

      10.1186/s12964-019-0478-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oncolytic potential of an E4-deficient adenovirus that can recognize the stabilization of AU-rich element containing mRNA in cancer cells.2018

    • Author(s)
      Yanagawa-Matsuda A, Mikawa Y, Habiba U, Kitamura T, Yasuda M, Towfik-Alam M, Kitagawa Y, Minowa K, Shindoh M, Higashino F
    • Journal Title

      Oncol Rep.

      Volume: 41(2) Pages: 954-960

    • DOI

      10.3892/or.2018.6865

    • NAID

      120006709288

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] HuR translocation to the cytoplasm of cancer cells in actin-independent manner.2018

    • Author(s)
      Habiba U., Kuroshima T., Yanagawa-Matsuda A., Kitamura T., Chowdhury A., Jehung J.P., Hossain E., Sano H., Kitagawa Y., Shindoh M., Higashino F.
    • Journal Title

      Experimental Cell Res.

      Volume: 369 Issue: 2 Pages: 218-225

    • DOI

      10.1016/j.yexcr.2018.05.021

    • NAID

      120006712704

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adenovirus infection induces HuR relocalization to facilitate virus replication2018

    • Author(s)
      Jehung JP, Kitamura T, Yanagawa-Matsuda A, Kuroshima T, Towfik A, Yasuda M, Sano H, Kitagawa Y, Minowa K, Shindoh M, Higashino F
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 495 Issue: 2 Pages: 1795-1800

    • DOI

      10.1016/j.bbrc.2017.12.036

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] アデノウイルスの感染によるP-bodyの形態変化とARE-mRNAの安定化2019

    • Author(s)
      松田 彩、黒嶋 雄志、北村 哲也、東野 史裕
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 歯冠周囲に歯原性上皮過誤腫が認められた埋伏智歯の一例2019

    • Author(s)
      松田 彩、北村 哲也、栗橋 可織、間石 奈湖、東野 史裕、樋田 京子
    • Organizer
      第30回 日本臨床口腔病理学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Promotion of metastasis via alteration of vascular endothelium by tumor exosome miRNA2018

    • Author(s)
      Morimoto M., Maishi N., Matsuda A., Kitamura T., Higashino F., Yokoyama A., Kitagawa Y., Hida K.
    • Organizer
      The 66th Annual Meeting of Japanese Association for Dental Research
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Adenovirus infection regulates stress granules and P bodies2018

    • Author(s)
      Jehung J. P., Kitamura T., Matsuda A., Higashino F., Hida K
    • Organizer
      The 66th Annual Meeting of Japanese Association for Dental Research
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Oncolytic potential of an E4-deficient adenovirus2018

    • Author(s)
      Matsuda A., Mikawa Y., Kitamura T., Higashino F
    • Organizer
      The 66th Annual Meeting of Japanese Association for Dental Research
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Combination effect of oncolytic adenovirus with ethanol for human cancer cells2018

    • Author(s)
      Ahmed I., Higashino F., Alam M. T., Kitamura T., Matsuda A., Minowa K
    • Organizer
      The 66th Annual Meeting of Japanese Association for Dental Research
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 破骨細胞におけるHuRの局在2018

    • Author(s)
      伊藤啓介、北村哲也、松田-柳川彩、東野史裕
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Enhancement of tumor cell death by combining cisplatin with E4orf6 gene deleted oncolytic adenovirus2018

    • Author(s)
      Umma Habiba, AyaYanagawa-Matsuda, Tetsuya Kitamura, Elora Hossain, Fumihiro Higashino
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] エナメル上皮腫のbudding形成の分子メカニズム解析2018

    • Author(s)
      篠原早紀、北村哲也、松田彩、高橋智美、飯塚正、東野史裕、樋田京子
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 診断に苦慮した下顎良性歯原性腫瘍の一例2018

    • Author(s)
      松田 彩,北村 哲也,和田 麻由美,高橋 智美,飯塚 正,、間石 奈湖,樋田 京子
    • Organizer
      第29回日本臨床口腔病理学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] がん細胞に対する腫瘍溶解アデノウイルスとエタノールの併用効果2018

    • Author(s)
      Ishrque A., Alam T. M., Kitamura T., Matsuda A., Iizuka T., Higashino F
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] E4領域の遺伝子を欠失した新たな腫瘍溶解アデノウイルスの開発2017

    • Author(s)
      松田 彩,東野 史裕,北村 哲也, 進藤 正信
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 腫瘍溶解アデノウイルスと5-FUとの併用効果の検討2017

    • Author(s)
      金山 純一,松田-柳川 彩,北村 哲也 ,北川 善政 ,東野 史裕
    • Organizer
      第28回日本臨床口腔病理学会総会・学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Evaluation of cytoskeleton dependent relocalization of HuR in cancer cells2017

    • Author(s)
      Umma Habiba, Tetsuya Kitamura, Aya yanagawa Matsuda, Masanobu Shindoh and Fumihiro Higashino
    • Organizer
      第28回日本臨床口腔病理学会総会・学術大会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2024-12-25  

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