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Cancer cell-specific imaging with the fluorescent probe responding by thymidine phosphorylase

Research Project

Project/Area Number 18K05360
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 37030:Chemical biology-related
Research InstitutionShibaura Institute of Technology

Principal Investigator

Hatano Akihiko  芝浦工業大学, 工学部, 教授 (10333163)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
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チミジンホスホリラーゼ / 過リン酸分解反応 / 蛍光プローブ / 癌診断 / 癌マーカー / 有機合成 / 血管新生因子 / TP応答型癌検出プローブ / 蛍光色素 / 蛍光共鳴エネルギー移動 / 酵素活性 / ピリミジンヌクレオシドホスホリラーゼ / ダンシル基 / 反応転換率 / 蛍光団 / 過リン酸分解 / 癌細胞 / 血管新生 / 蛍光イメージング / 癌
Outline of Final Research Achievements

AAngiogenesis is the first step in the growth of cancer cells, and if this stage can be detected, it will lead to early detection. Thymidine phosphorylase (TP) is an angiogenic factor and is involved in the growth and metastasis of cancer cells. We considered that TP observation would be a marker for early detection of cancer cells. In this study, we developed a fluorescent probe that responds to the enzymatic activity of TP, which is an angiogenesis factor, and aimed to visualize the early development process of cancer cells. First, as a diagnostic agent whose fluorescence intensity changes with TP, we attempted to covalently bond a dansyl group as a fluorescent dye and a dabsyl group as a quenching agent to thymidine. When the TP response activity was evaluated using the synthesized probe, it was found that the phosphorolysis decomposition reaction proceeded by about 45% in 1 hour.

Academic Significance and Societal Importance of the Research Achievements

日本人の死因一位は癌である(約30%)。消化器官の内視鏡観察時に癌の疑いのある組織は,ヨード染色による目視判定が行われ,次に対象組織が採取されて病理検査が行われる。ヨード染色は簡便であるが副作用が問題である。癌の判定は組織を少量採取し,病理検査の結果を経て診断と癌組織の切除範囲が決定されるため,時間と労力がかかる。術中の薬剤塗布検査が病理検査と同じ精度で癌組織を検出できれば,癌組織の切除はリアルタイムで実施可能となり,正確,迅速,患者への負担軽減と再発防止に繋がると考えられる。そのため,簡単に癌細胞の場所を診断できるような新しいプローブ分子の開発が望まれている。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (17 results)

All 2022 2020 2019 2018 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (11 results) (of which Int'l Joint Research: 2 results) Remarks (1 results)

  • [Journal Article] Parallel motif triplex formation via a new, bidirectional hydrogen bonding pattern incorporating a synthetic cyanuryl nucleoside into the sense chain2020

    • Author(s)
      Hatano, Akihiko; Shimazaki, Kei; Otsu, Maina; Kawai, Gota
    • Journal Title

      RSC Advances

      Volume: 10 Issue: 38 Pages: 22766-22774

    • DOI

      10.1039/d0ra03889j

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A single-use ceramic-based electrochemical sensor chip using molecularly imprinted carbon paste electrode2020

    • Author(s)
      Aaryashree; Takeda, Yuuto; Kanai, Momoe; Hatano, Akihiko; Yoshimi, Yasuo; Kida, Masahito
    • Journal Title

      Sensors

      Volume: 20 Issue: 20 Pages: 5847-5847

    • DOI

      10.3390/s20205847

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Bio-catalytic synthesis of unnatural nucleosides possessing a large functional group such as a fluorescent molecule by purine nucleoside phosphorylase,2019

    • Author(s)
      A. Hatano, H. Wakana, N. Terado, A.Kojima, C. Nishioka, Y. Iizuka, T. Imaizumi, S. Uehara,
    • Journal Title

      Catalysis Science & Technolog

      Volume: 9 Issue: 18 Pages: 5122-5129

    • DOI

      10.1039/c9cy01063g

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Use of a deoxynojirimycin-fluorophore conjugate as a cell-specific imaging probe targeting α-glucosidase on cell membranes2019

    • Author(s)
      Akihiko Hatano, Yuichi Kanno, Yuya Kondo, Yuta Sunaga, Hatsumi Umezawa, Koji Fukui
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 27 Issue: 5 Pages: 859-864

    • DOI

      10.1016/j.bmc.2019.01.032

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis of a protected ribonucleoside phosphoramidite-linked spin label via an alkynyl chain at the 5′ position of uridine2019

    • Author(s)
      A. Hatano, N, Terado, Y. Kanno, T. Nakamura, G. Kawai
    • Journal Title

      Synthetic Communications

      Volume: 49 Issue: 1 Pages: 136-145

    • DOI

      10.1080/00397911.2018.1545033

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Presentation] レーザーマイクロダイセクション装置によるがん細胞特異的に見られる 核内封入体構成成分としての液滴オルガネラの単離2022

    • Author(s)
      水口 海, 幡野明彦, 八谷如美
    • Organizer
      日本化学会第102春季年会(2022)
    • Related Report
      2021 Annual Research Report
  • [Presentation] ピリミジンヌクレオシドホスホリラーゼによるリボース部位修飾 ヌクレオシドの反応性2022

    • Author(s)
      間弓 利勇・大槻 晃一・幡野明彦
    • Organizer
      日本化学会第102春季年会(2022)
    • Related Report
      2021 Annual Research Report
  • [Presentation] 核酸代謝酵素PyNPによるヌクレオシドへのプリン類似体ベンゾイミダゾール化合物の導入2022

    • Author(s)
      松坂理希・林田拓巳・幡野明彦
    • Organizer
      日本化学会第102春季年会(2022)
    • Related Report
      2021 Annual Research Report
  • [Presentation] SYNTHESIS OF UNNATURAL NUCLEOSIDES LINKED FLUORESCENT GROUP BY NUCLEOSIDE METABOLIC ENZYME2020

    • Author(s)
      Hiroyuki Wakana, Akihiko Hatano
    • Organizer
      14th South East Asian Technical University Consortium Symposium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 核酸代謝酵素類を用いた蛍光部位を持つ非天然ヌクレオシドの合成と反応性の評価2019

    • Author(s)
      若菜 浩幸、鈴木 康、幡野 明彦
    • Organizer
      生体触媒シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] 蛍光部位を持つ非天然ヌクレオシドの核酸代謝酵素を用いた合成と反応性の評価2019

    • Author(s)
      若菜浩幸,鈴木康,寺戸那奈恵,幡野明彦
    • Organizer
      バイオ関連化学シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] Synthesis of unnatural nucleosides containing fluorescent group by using nucleic acid metabolic enzyme2018

    • Author(s)
      H. Wakana, N. Terado, A. Hatano
    • Organizer
      15th Japan-China-Korea Joint Symposium on Enzyme Engineering
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 核酸代謝酵素を用いた修飾プリンのヌクレオシドへの導入2018

    • Author(s)
      鈴木康、若菜浩幸、飯塚佑、幡野明彦
    • Organizer
      生体触媒シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] Development of the imaging probe targeting for thymidine phosphorylase as angiogenic factor of cancer2018

    • Author(s)
      Wakana, Hiroyuki, Hatano, Akihiko
    • Organizer
      生体触媒シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] 血管新生因子であるチミジンホスホリラーゼに応答する蛍光プローブの開発2018

    • Author(s)
      若菜浩幸、幡野明彦
    • Organizer
      酵素工学研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 核酸代謝酵素を用いた蛍光部位導入非天然ヌクレオシドの合成2018

    • Author(s)
      若菜 浩幸,幡野 明彦
    • Organizer
      第12回バイオ関連化学シンポジウム
    • Related Report
      2018 Research-status Report
  • [Remarks] 芝浦工業大学工学部材料工学科生体分子化学研究室

    • URL

      http://www.sic.shibaura-it.ac.jp/~a-hatano/a-hatano/a-hatano.html

    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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