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Analysis of radio-resistant and highly invasive cells with using real-time imaging system

Research Project

Project/Area Number 15K19833
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Radiation science
Research InstitutionNational Institutes for Quantum and Radiological Science and Technology

Principal Investigator

Fujita Mayumi  国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 放射線障害治療研究部, 主任研究員(定常) (80580331)

Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords放射線がん治療 / 細胞浸潤 / 放射線照射 / 放射線抵抗浸潤細胞 / 炭素線照射 / リアルタイム観察
Outline of Final Research Achievements

Radiotherapy is one of the important therapeutic option for cancer treatment. However, metastasis is still the main cause of mortality in cancer patients. We previously reported that number of invasive cells were increased after C-ion irradiation on human pancreatic cancer cell line, PANC-1. In order to block these radio-resistant highly invasive PANC-1 cells, in this study, we established the live cell imaging system and examined the specific phenotype of radiation-survived PANC-1 cells. We found that a distinct population of high invasive cells within whole-cultured PANC-1, and these cells were also resistant to radiation. These radio-resistant highly invasive cells experienced higher oxidative stress, showing lower GSH/GSSG ratios, but also greater resistance to it. Overall, we proposed that the treatment of PANC-1 cells with L-buthionine-sulfoximine (BSO), the inhibitor of GSH biosynthesis, was effective to reduce the intercellular GSH content as well as their invasion.

Academic Significance and Societal Importance of the Research Achievements

放射線治療は侵襲のない局所療法であり重要ながん治療法のひとつであるが、今後、生存率をさらに向上させるためには、治療後の再発及び浸潤、転移をいかにして抑制できるかが課題である。我々はこれまでに、炭素イオン線照射はX線に比べ、大多数の癌細胞株の浸潤抑制に効果的であるが、PANC-1など特定の細胞株では浸潤細胞の数が増加することを見いだした。照射によるストレスに打ち勝ち、高い浸潤能を示す放射線抵抗性浸潤細胞は、放射線治療後の再発や浸潤転移につながる可能性が考えられ、これら細胞を効率良く抑制することは極めて重要である。よって本研究の結果は、放射線治療の発展につながる社会的意義が高い成果である。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (12 results)

All 2019 2018 2017 2016 2015 Other

All Int'l Joint Research (2 results) Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 5 results,  Acknowledgement Compliant: 3 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] The National Institutes of Health (NIH)(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] The National Institutes of Health (NIH)(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Role of nitric oxide in pancreatic cancer cells exhibiting the invasive phenotype2019

    • Author(s)
      Fujita Mayumi、Somasundaram Veena、Basudhar Debashree、Cheng Robert Y.S.、Ridnour Lisa A.、Higuchi Harumi、Imadome Kaori、No Jae Hong、Bharadwaj Gaurav、Wink David A.
    • Journal Title

      Redox Biology

      Volume: 22 Pages: 101158-101158

    • DOI

      10.1016/j.redox.2019.101158

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Understanding the tumour micro‐environment communication network from an NOS2/COX2 perspective2018

    • Author(s)
      Basudhar Debashree、Bharadwaj Gaurav、Somasundaram Veena、Cheng Robert Y S、Ridnour Lisa A、Fujita Mayumi、Lockett Stephen J、Anderson Stephen K、McVicar Daniel W、Wink David A
    • Journal Title

      British Journal of Pharmacology

      Volume: 176 Issue: 2 Pages: 155-176

    • DOI

      10.1111/bph.14488

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Molecular Mechanisms of Nitric Oxide in Cancer Progression, Signal Transduction and Metabolism2018

    • Author(s)
      Veena Somasundaram, Debashree Basudhar, Gaurav Bharadwaj, Jae Hong No, Lisa A. Ridnour, Robert Y.S Cheng, Mayumi Fujita, Douglas D. Thomas, Stephen Anderson, Daniel W. McVicar, David A. Wink
    • Journal Title

      Antioxidants and Redox Signaling

      Volume: in press Issue: 8 Pages: 1124-1143

    • DOI

      10.1089/ars.2018.7527

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Metabolic characterization of invaded cells of the pancreatic cancer cell line, PANC-1.2017

    • Author(s)
      Mayumi Fujita, Kaori Imadome, Takashi Imai
    • Journal Title

      Cancer science

      Volume: in press Issue: 5 Pages: 961-971

    • DOI

      10.1111/cas.13220

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Irradiation induces diverse changes in invasive potential in cancer lines2015

    • Author(s)
      Fujita Mayumi, Yamada Shigeru, Imai Takashi.
    • Journal Title

      Semin Cancer Biol

      Volume: 35 Pages: 45-52

    • DOI

      10.1016/j.semcancer.2015.09.003

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Carbon-ion irradiation suppresses migration and invasiveness of human pancreatic carcinoma cells MIAPaCa-2 via Rac1 and RhoA degradation2015

    • Author(s)
      Fujita, M., Imadome, K., Shoji, Y., Isozaki, T., Endo, S., Yamada, S., and Imai, T.
    • Journal Title

      International Journal of Radiation Oncology Biology Physics

      Volume: 未確定 Issue: 1 Pages: 173-180

    • DOI

      10.1016/j.ijrobp.2015.05.009

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Role of Nitric Oxide in Pancreatic Cancer Cells Exhibiting the Invasive Phenotype2018

    • Author(s)
      Mayumi Fujita, Veena Somasundaram, Debashree Basudhar, Robert Y.S Cheng, Lisa A, David A. Wink
    • Organizer
      The 18th Annual CCR-FY1 Colloquium
    • Related Report
      2017 Research-status Report
  • [Presentation] 癌細胞の集団遊走におけるミトコンドリアの細胞内局在2016

    • Author(s)
      今留 香織, 藤田 真由美
    • Organizer
      第39回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Role of Rac1 activity in invasiveness of human pancreatic cancer cell lines irradiated with carbon-ion beams2015

    • Author(s)
      Mayumi Fujita, Takashi Imai
    • Organizer
      The 74th Annual Meeting of the Japanese Cancer Association (JCA)
    • Place of Presentation
      Nagoya-shi
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Effects of Irradiation on Cellular Invasiveness with Regard to Cancer Cell Heterogeneity2015

    • Author(s)
      Mayumi Fujita, Kaori Imadome, Yoshimi Shoji, Takashi Imai
    • Organizer
      15th International Congress of Radiation Research (ICRR 2015)
    • 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: 2020-03-30  

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