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Elucidation of the action mechanism of combined treatment with X-ray irradiation and 5-aminolevulinic acid by trantcriptome analysis

Research Project

Project/Area Number 25293270
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Radiation science
Research InstitutionNational Institute of Advanced Industrial Science and Technology

Principal Investigator

Takahashi Junko  国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (80415702)

Co-Investigator(Kenkyū-buntansha) 森 崇  岐阜大学, 応用生物科学部, 教授 (40402218)
岩橋 均  岐阜大学, 応用生物科学部, 教授 (60356540)
Project Period (FY) 2013-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2015: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2014: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2013: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Keywords放射線治療 / X線 / 放射線増感剤 / 5-アミノレブリン酸 / ポルフィリン / がん治療 / 放射線力学療法 / 光線力学療法 / プロトポルフィリン / 増感剤 / マイクロアレイ / アミノレブリン酸 / 放射線 / 放射線療法
Outline of Final Research Achievements

Combined treatment with 5-aminolevulinic acid (ALA) and X-rays improves tumor suppression in vivo. This is because the accumulated protoporphyrin IX from ALA enhances the generation of ROS by the X-ray irradiation. In the present study, a high-energy medical linear accelerator was used instead of a non-medical low energy X-ray irradiator, which had been previously used. Tumor-bearing mice implanted with B16-BL6 melanoma cells were treated with fractionated doses of irradiation (in total, 20 or 30 Gy), using two types of X-ray irradiator after ALA administration. Suppression of tumor growth was enhanced with X-ray irradiation in combination with ALA treatment compared with X-ray treatment alone, using both medical and non-medical X-ray irradiators. “Radiodynamic therapy” using radiation from medical linacs as a physical driving force, rather than the light used in photodynamic therapy, may have potential clinical applications.

Academic Significance and Societal Importance of the Research Achievements

本課題の目標は、光線力学療法の励起メカニズムと類似しているが、光に替わりX線を用い、放射線の腫瘍選択性を高め、深部癌の治療に有効な「放射線力学療法」を開発し、今までの放射線治療では治療できなかったがんの治療に役立てることである。放射線力学療法に用いる放射線増感剤は低分子有機化合物であり、この様な化合物の放射線応答性に関する研究は独創的であり、世界的にも類似の研究はほとんど進められていない。

Report

(6 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (14 results)

All 2018 2017 2016 2015

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) (of which Int'l Joint Research: 2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Verification of radiodynamic therapy by medical linear accelerator using a mouse melanoma tumor model2018

    • Author(s)
      Takahashi Junko、Murakami Mami、Mori Takashi、Iwahashi Hitoshi
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 27281-9

    • DOI

      10.1038/s41598-018-21152-z

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Luteolin as reactive oxygen generator by X-ray and UV irradiation2018

    • Author(s)
      Toyama Michiru、Mori Takashi、Takahashi Junko、Iwahashi Hitoshi
    • Journal Title

      Radiation Physics and Chemistry

      Volume: 146 Pages: 11-18

    • DOI

      10.1016/j.radphyschem.2017.12.022

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Introduction to 5-Aminolevulinic Acid-Protoporphyrin IXMediated Radiodynamic Therapy (RDT)2018

    • Author(s)
      Junko Takahashi、Hitoshi Iwahashi
    • Journal Title

      Clinics in Oncology

      Volume: 2 Pages: 13301-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combined treatment with X-ray irradiation and 5-aminolevulinic acid elicits better transcriptomic response of cell cycle-related factors than X-ray irradiation alone.2016

    • Author(s)
      J. Takahashi, M. Misawa, H. Iwahashi
    • Journal Title

      International Journal of Radiation Biology

      Volume: 12 Issue: 12 Pages: 774-789

    • DOI

      10.1080/09553002.2016.1230240

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Gene expression profiling can predict the fate of HeLa cells exposed to X-ray irradiation with or without protoporphyrin accumulation2015

    • Author(s)
      J. Takahashi, M. Misawa, H. Iwahashi
    • Journal Title

      Genomics Data

      Volume: 5 Pages: 192-194

    • DOI

      10.1016/j.gdata.2015.05.044

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transcriptome Analysis of Porphyrin-Accumulated and X-Ray-Irradiated Cell Cultures under Limited Proliferation and Non-Lethal Conditions2015

    • Author(s)
      Junko Takahashi, Masaki Misawa, Hitoshi Iwahashi
    • Journal Title

      Microarrays

      Volume: 4 Pages: 25-40

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 担癌マウスに対する5-アミノレブリン酸放射線力学療法(RDT)の線量低減効果2016

    • Author(s)
      高橋淳子、村上麻美、森崇、岩橋均
    • Organizer
      ポルフィリン-ALA学会
    • Place of Presentation
      東京大学、東京、日本
    • Year and Date
      2016-04-22
    • Related Report
      2016 Annual Research Report
  • [Presentation] Screening for new non-toxic X-ray responsive substance2016

    • Author(s)
      Michiru Toyama, Takashi Mori, Yui Mizowaki, Junko Takahashi, Hitoshi Iwahashi
    • Organizer
      日本農芸化学会
    • Place of Presentation
      札幌コンベンションセンター(北海道・札幌)
    • Year and Date
      2016-03-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] Combined treatment with X-ray irradiation and 5-aminolevurinic acid inhibits tumor growth in mouse tumor models2015

    • Author(s)
      Junko Takahashi, Masaki Misawa, Hitoshi Iwahashi
    • Organizer
      The 3rd International ALA and Porphyrin Symposium
    • Place of Presentation
      ハワイ(アメリカ)
    • Year and Date
      2015-12-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Transcriptome analysis of porphyrin-accumulated and X-ray irradiated cell cultures2015

    • Author(s)
      Junko Takahashi, Masaki Misawa, Hitoshi Iwahashi
    • Organizer
      The 3rd International ALA and Porphyrin Symposium
    • Place of Presentation
      ハワイ(アメリカ)
    • Year and Date
      2015-12-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ALAを利用した放射線増感の可能性2015

    • Author(s)
      高橋淳子、三澤雅樹、岩橋均
    • Organizer
      第5回ポルフィリン-ALA学会年会
    • Place of Presentation
      東京
    • Year and Date
      2015-04-25 – 2015-04-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 担癌マウスを用いた5-アミノレブリン酸のX線増感効果の検証2015

    • Author(s)
      森崇、村上麻美、岩橋均、三澤雅樹、高橋淳子
    • Organizer
      第5回ポルフィリン-ALA学会年会
    • Place of Presentation
      東京
    • Year and Date
      2015-04-25 – 2015-04-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] ALA投与による放射線増感効果 -細胞応答の網羅的遺伝子発現解析-2015

    • Author(s)
      岩橋均、森崇、村上麻美、三澤雅樹、高橋淳子
    • Organizer
      第5回ポルフィリン-ALA学会年会
    • Place of Presentation
      東京
    • Year and Date
      2015-04-25 – 2015-04-26
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] ALAと鉄剤の併用による放射線増感効果2017

    • Inventor(s)
      高橋淳子、岩橋均、成田善孝、井垣浩、田中徹、石塚昌宏、原武史
    • Industrial Property Rights Holder
      高橋淳子、岩橋均、成田善孝、井垣浩、田中徹、石塚昌宏、原武史
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-253583
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report

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Published: 2013-05-21   Modified: 2020-03-30  

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