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Applied of RNA stabilization system-based oncolytic virus to oral cancer

Research Project

Project/Area Number 17H04401
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionHokkaido University

Principal Investigator

Higashino Fumihiro  北海道大学, 歯学研究院, 准教授 (50301891)

Co-Investigator(Kenkyū-buntansha) 北村 哲也  北海道大学, 医学研究院, 客員研究員 (00451451)
松田 彩  北海道大学, 歯学研究院, 特任助教 (60514312)
安田 元昭  北海道大学, 歯学研究院, 准教授 (90239765)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywordsアデノウイルス / 口腔がん / 腫瘍 / 溶解 / ARE-mRNA / 腫瘍溶解ウイルス / 癌 / トランスレーショナルリサーチ / ARE-mRNA
Outline of Final Research Achievements

In this study, we investigated the effects of the newly developed oncolytic adenovirus Ad + AU. Ad + AU replicated more efficiently in cancer cells than in normal cells, and further induced cell death. Ad + AU was suggested to be an oncolytic virus that is more effective than the clinically applied virus ONYX-015. As a result of examining the effect of Ad + AU using animals, it was clarified that Ad + AU has an oncolytic effect even in a cancer-bearing model. Furthermore, the combined effect of the anticancer drug and Ad + AU was examined, and when used in combination with paclitaxel, the anticancer activity of Ad + AU was enhanced. These results indicate that Ad + AU is a useful oncolytic virus.

Academic Significance and Societal Importance of the Research Achievements

本研究では、Ad+AUの腫瘍溶解効果を確立することができた。多くの種類の腫瘍溶解ウイルスが開発されたが、mRNAの安定化機構を応用したウイルスは我々独自の研究である。抗がん剤など、これまでのがんの治療法は、患者に対して苦痛や副作用が伴うことが多いが、Ad+AUを用いた治療法は、副作用がなく、使用法も簡便で、他のがん治療法との併用も容易なので、非常に有用な治療法になると期待できる。また、アデノウイルスは病原性が低く、遺伝子治療用のベクターとしての実績もあり、安全性が非常に高く、実用化しやすい。さらに、アデノウイルスは複製効率も高く、生産方法も簡便で安価なため、企業化の面でもメリットが高い。

Report

(4 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (24 results)

All 2021 2020 2019 2018 2017 Other

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) (of which Invited: 1 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 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 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Conditionally Replicative Adenovirus Controlled by the Stabilization System of AU-Rich Elements Containing mRNA2020

    • Author(s)
      Mikawa Yohei、Towfik Alam Mohammad、Hossain Elora、Yanagawa-Matsuda Aya、Kitamura Tetsuya、Yasuda Motoaki、Habiba Umma、Ahmed Ishraque、Kitagawa Yoshimasa、Shindoh Masanobu、Higashino Fumihiro
    • Journal Title

      Cancers

      Volume: 12 Issue: 5 Pages: 1205-1205

    • DOI

      10.3390/cancers12051205

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Advantages of Using Paclitaxel in Combination with Oncolytic Adenovirus Utilizing RNA Destabilization Mechanism2020

    • Author(s)
      Hossain Elora、Habiba Umma、Yanagawa-Matsuda Aya、Alam Arefin、Ahmed Ishraque、Towfik Alam Mohammad、Yasuda Motoaki、Higashino Fumihiro
    • Journal Title

      Cancers

      Volume: 12 Issue: 5 Pages: 1210-1210

    • DOI

      10.3390/cancers12051210

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhanced oncolytic activity of E4orf6-deficient adenovirus by facilitating nuclear export of HuR.2020

    • Author(s)
      Ahmed I., Towfik Alam M., Yanagawa-Matsuda A., Hossain E., Kitamura T., Minowa K., Higashino F.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 529 Pages: 494-499

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 口腔扁平上皮がん細胞におけるELAVL2の発現2020

    • Author(s)
      畑中知之、三河洋平、東野史裕、鄭漢忠、安田元昭
    • Journal Title

      北海道歯学雑誌

      Volume: 40 Pages: 79-86

    • NAID

      120006826284

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [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
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adenovirus infection induces HuR relocalization to facilitate virus replication.2018

    • Author(s)
      Jehung J.P., 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 Pages: 1795-1800

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression patterns of ALDH1 and podoplanin predict the risk of malignant transformation in oral leukoplakia.2017

    • Author(s)
      Habiba U, Hida K, Kitamura T, Yanagawa-Matsuda A, Higashino F,Ito YM, Ohiro Y, Totsuka Y, Shindoh M
    • Journal Title

      Oncology Letters

      Volume: 13 Issue: 1 Pages: 321-328

    • DOI

      10.3892/ol.2016.5379

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Radiation therapy enhances the potential of the oncolytic virus in the treatment of osteosarcoma.2021

    • Author(s)
      E. Hossain, F. Higashino
    • Organizer
      AACR Radiation Science and Medicine
    • Related Report
      2019 Annual Research Report
  • [Presentation] 腫瘍溶解アデノウイルスの 効果増強のための試み2020

    • Author(s)
      松田彩、加藤泰史、北村哲也、間石奈湖、樋田京子、東野史裕
    • Organizer
      第109回日本病理学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] mRNAの安定化機構を応用した新しい腫瘍溶解アデノウイルスの開発と解析2020

    • Author(s)
      加藤泰史、北川善政、東野史裕
    • Organizer
      第65回日本口腔外科学会総会・学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 新たに開発した腫瘍溶解アデノウイルスの効果の検討2019

    • Author(s)
      加藤泰史、松田彩、間石奈湖、北村哲也、樋田京子、北川善政、東野史裕
    • Organizer
      第73回 日本口腔科学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 破骨細胞の分化に対するRNA結合タンパクHuRの役割2019

    • Author(s)
      養田稔、伊藤啓介、松田彩、北村哲也、鄭漢忠、東野史裕
    • Organizer
      第73回 日本口腔科学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 破骨細胞の分化・機能とRNA結合タンパクHuRの細胞質局在2019

    • Author(s)
      養田稔、伊藤啓介、松田彩、間石奈湖、北村哲也、樋田京子、鄭漢忠、東野史裕
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2018 Annual Research Report
  • [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
      2018 Annual Research Report
  • [Presentation] Evaluation of the efficacy of newly developed oncolytic adenovirus.2019

    • Author(s)
      Hossain E, Habiba U, Kitamura T, Matsuda AY, Elora Hossain, Higashino F
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Oncolytic potential of an E4-deficient adenovirus that can recognize the stabilization of AU-rich element containing mRNA in cancer cells.2019

    • Author(s)
      Fumihiro Higashino, Aya Yanagawa-Matsuda, Mohammad Towfik-Alam, Tetsuya Kitamura
    • Organizer
      第25回日本遺伝子細胞治療学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 新しいタイプの腫瘍溶解ウイルスの開発‐腫瘍以外の疾患にも応用できるか‐2019

    • Author(s)
      東野史裕
    • Organizer
      第50回北陸小児癌講演会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [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 Annual Research Report
  • [Presentation] Evaluation of cytoskeleton dependent relocalization of HuR in cancer cells2017

    • Author(s)
      Habiba U, Kitamura T, Yanagawa-Matsuda A, Shindoh M, Higashino F
    • Organizer
      第29回日本臨床口腔病理学会
    • Related Report
      2017 Annual Research 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、柳川-松田 彩、北村哲也、北川善政、東野史裕
    • Organizer
      第29回日本臨床口腔病理学会
    • Related Report
      2017 Annual Research Report
  • [Remarks] RNAの安定化を利用!がん細胞を破壊するウイルスを開発その2

    • URL

      https://www.hokudai.ac.jp/news/2020/05/rna2.html

    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 眼内血管新生病または眼内増殖性疾患の治療または予防薬2020

    • Inventor(s)
      東野史裕
    • Industrial Property Rights Holder
      東野史裕
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 改変アデノウイルス及びこれを含む医薬2020

    • Inventor(s)
      2020/03/19
    • Industrial Property Rights Holder
      2020/03/19
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2018 Annual Research Report
    • Overseas

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Published: 2017-04-28   Modified: 2023-12-25  

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