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Attempt to enhance the effect of oncolytic adenovirus.

Research Project

Project/Area Number 19K19221
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionHokkaido University

Principal Investigator

Alam Mohammad Towfik  北海道大学, 歯学研究院, 学術研究員 (60641694)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsアデノウイルス / 口腔がん / 腫瘍 / 溶解 / エタノール / 腫瘍溶解ウイルス / 癌 / トランスレーショナルリサーチ
Outline of Research at the Start

2019年度は、口腔がん細胞への効果検証を中心に解析する。口腔がん培養細胞をエタノール処理し、細胞質に存在するHuRが最も多いエタノールの条件を決定する。次に、その条件下で、Ad+AUの口腔がんに対する腫瘍溶解効果、即ち増殖ウイルス数を確定し、XTT assayにより細胞死を検討する。2020年度は、既存の腫瘍溶解ウイルスONYX-015との比較を行う。ONYX-015とAd+AU+エタノールでどちらがその効果が増強されるか、上述と同様に検討する。

Outline of Final Research Achievements

In this study, we investigated whether the oncolytic effect of oncolytic adenovirus Ad + AU was enhanced by ethanol treatment. After determining the optimum concentration of ethanol, the oncolytic effect of Ad + AU on cancer cells was examined. The addition of ethanol activated both virus growth efficiency and cell death by Ad + AU. Furthermore, tumors of cancer cells were prepared in nude mice, and Ad + AU and ethanol were administered to examine the enhancement of the oncolytic effect in vivo. Ad + AU suppressed the growth of this tumor, and the system treated with both virus and ethanol further suppressed the growth of the tumor. These results indicate that ethanol can activate the oncolytic activity of Ad + AU.

Academic Significance and Societal Importance of the Research Achievements

本研究では、エタノールによるAd+AUの腫瘍溶解効果増強を証明することができた。この特徴は他の多くの腫瘍溶解ウイルスにはないこのウイルス独自の有利性である。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

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

    (4 results)

All 2020 2019

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

  • [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
      2020 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
      2020 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
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [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
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2022-12-28  

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