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Assessment of the relationship of the radiation sensitizing agents and tumor microenvironments

Research Project

Project/Area Number 15K15454
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Radiation science
Research InstitutionKyoto University

Principal Investigator

Yoshimura Michio  京都大学, 医学研究科, 講師 (40597936)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywordsradiation sensitizer / tumor microenvironment / 放射線増感 / 放射線治療 / 分子標的薬 / 微小環境
Outline of Final Research Achievements

Hypoxic and stroma-rich microenvironments, characteristic features of pancreatic cancers, are associated with a poor prognosis. We found that pancreatic cancer cells secreted more Sonic hedgehog protein (SHH) under hypoxia. The SHH protein secreted from pancreatic cancer cells under hypoxic conditions promoted the growth of fibroblasts by stimulating their Sonic hedgehog signaling pathway. These results suggest that the increased SHH is potentially responsible for the formation of stroma-rich microenvironments in pancreatic cancers, therefore providing a rational basis to target it. RAS/RAF/MEK/ERK pathway is overexpressed in a variety of cancer, and targeting this pathway is considered to be one of the most promising anticancer agents. We found that MEK inhibition showed radiosensitizing effect on a pancreatic cancer cell, MIA PACA-2. MEK inhibition could be a target of radiosensitizing anticancer agents.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (4 results)

All 2018 2017 2015

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] HIF-1 maintains a functional relationship between pancreatic cancer cells and stromal fibroblasts by upregulating expression and secretion of Sonic hedgehog2018

    • Author(s)
      Katagiri Tomohiro、Kobayashi Minoru、Yoshimura Michio、Morinibu Akiyo、Itasaka Satoshi、Hiraoka Masahiro、Harada Hiroshi
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 12 Pages: 10525-10535

    • DOI

      10.18632/oncotarget.24156

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] UCHL1-HIF-1 axis-mediated antioxidant property of cancer cells as a therapeutic target for radiosensitization2017

    • Author(s)
      Nakashima Ryota、Goto Yoko、Koyasu Sho、Kobayashi Minoru、Morinibu Akiyo、Yoshimura Michio、Hiraoka Masahiro、Hammond Ester M.、Harada Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 6879-6879

    • DOI

      10.1038/s41598-017-06605-1

    • NAID

      120006355750

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PLK1 blockade enhances therapeutic effects of radiation by inducing cell cycle arrest at the mitotic phase.2015

    • Author(s)
      Inoue M, Yoshimura M, Kobayashi M, Morinibu A, Itasaka S, Hiraoka M, *Harada H.
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 15666-15666

    • DOI

      10.1038/srep15666

    • NAID

      120005753886

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] PLK1 blockade enhances therapeutic effect of radiation by inducing cell cycle arrest at mitotic phase2015

    • Author(s)
      Michio YOSHIMURA, Minoru INOUE, Minoru KOBAYASHI, Satoshi ITASAKA, Hiroshi HARADA, Masahiro HIRAOKA
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-05-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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