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The secret of radiation-surviving cell : multidisciplinary approach to eradicate cancer

Research Project

Project/Area Number 20390319
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionHokkaido University

Principal Investigator

NISHIOKA Takeshi  Hokkaido University, 大学院・保健科学研究院, 教授 (80271659)

Co-Investigator(Kenkyū-buntansha) YASUDA Motoaki  北海道大学, 大学院・歯学研究科, 准教授 (90239765)
HAGA Hisahi  北海道大学, 大学院・理学研究院, 准教授 (00292045)
TUTSMI Kaori  北海道大学, 大学院・保健科学研究院 (80344505)
SAKAI Masaharu  北海道大学, 大学院・保健科学研究院 (50162269)
HOMMA Akiniro  北海道大学, 大学院・医学研究科 (30312359)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2010: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2008: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
Keywords放射線生物学 / irradiation / p16 / repopulation / mitosis / MMP / HIF1-alpha / radiation / cancer stem cell / cell movement / Radiotherapy / TGFB-1 / 細胞形態 / 細胞運動
Research Abstract

Treatment with any cytotoxic agent can trigger surviving cells in a tumor to divide faster than before. This phenomenon is widely recognized as "repopulation". To better clarify the mechanism, gene expression profiling and pathological experiments were performed. A mouse fibrosarcoma cell line, QRsP, was used. Cells were irradiated with 10 Gy. Colony assay and cloning were performed. Six clones were established. cDNA analysis was performed on the clone that showed the largest number of colonies on the 2nd 10 Gy irradiation. Mouse transplantation experiment was then carried out. cDNA analysis showed that cyclin-dependent kinase inhibitors, p16 and p57 were down-regulated ; 14.8- and 12.0-fold, respectively for the tolerant clone. Matrix metalloproteinase 3 and 13 were up-regulated ; 22.5- and 25.8-fold, respectively. Transplantation ratio was 100% (5/5) for the tolerant clone whereas it was 40% (2/5) for the parent. Under light microscope, the mean mitotic cell number was 4.0+/-3.9 for the parent, and 12.8+/-3.4 for the tolerant clone (p<0.01, Student's t-test). This study implies that repopulation is not a temporary reaction to irradiation. It is caused probably by "clonal" gene-expression changes, though it remains unknown whether the changes are attributable to tolerant cell selection or to gene mutation/modification.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (14 results)

All 2011 2010 2009 2008

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (2 results)

  • [Journal Article] Hypoxic-inducible factor-1α might up-regulate matrix metalloproteinase in subclones that survive 10-Gy X-irradiation.2011

    • Author(s)
      Nishioka T, Yamazaki R.
    • Journal Title

      Jpn J Radiol. 29

      Pages: 226-7

    • NAID

      50008069770

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Radiation-induced cancer cell repopulation : a possible mechanism implied by experiments using transplantable mouse-derived sarcoma cell line.2011

    • Author(s)
      Nishioka T, Yasuda M, Takeshima T, Haga H, Miyai Y, Shibata K, Yamazaki R, Shirato H, Teduka M, Date H.
    • Journal Title

      Cell Struct Funct. 36

      Pages: 13-20

    • NAID

      40019163767

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Radiation-induced Cancer Cell Repopulation : A Possible Mechanism Implied by Experiments Using Transplantable Mouse-derived Sarcoma Cell Line.2011

    • Author(s)
      Takeshi Nishioka
    • Journal Title

      Cell Structure and Function

      Volume: 36 Pages: 13-20

    • NAID

      40019163767

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cesium implant for tongue carcinoma with a thickness of 1.5cm or more : cases successfully treated with a Modified Manchester System.2010

    • Author(s)
      Nishioka T, Fujino M, Homma A, Yamashita T, Sato A, Ohmori K, Obinata K, Shirato H, Notani K, Nishio M.
    • Journal Title

      Yonsei Med J. 51

      Pages: 557-61

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Integrin betal-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix.2010

    • Author(s)
      Ishihara S, Haga H, Yasuda M, Mizutani T, Kawabata K, Shirato H, Nishioka T.
    • Journal Title

      Biochem Biophys Res. 396

      Pages: 651-5

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synchronous monitoring of external/internal respiratory motion : validity of respiration-gated radiotherapy for liver tumors.2009

    • Author(s)
      Nishioka T, Nishioka S, Kawahara M
    • Journal Title

      Japanese journal of Radiology 27

      Pages: 285-289

    • NAID

      50007342472

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nishioka T, Miyai Y, Haga H, Kawabata K, Shirato H, Homma A, Shibata K, and Yasuda M2009

    • Author(s)
      Nishioka T, Miyai Y, Haga H
    • Journal Title

      Cell Struct Funct 34

      Pages: 17-22

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Superselective high-dose cisplatin infusion with concomitant radiotherapy in patients with advanced cancer of the nasal cavity and paranasal sinuses : a single institution experience.2009

    • Author(s)
      Homma A, Oridate N, Suzuki F, Taki S, Asano T, Yoshida D, Onimaru R, Nishioka T
    • Journal Title

      Cancer 115

      Pages: 4705-14

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Superselective high-dose cisplatin infusion with concomitant radiotherapy in patients with advanced cancer of the nasal cavity and paranasal sinuses : a single institution experience.2009

    • Author(s)
      Tsutsumi K, Tsuda M, Yazawa N, Nakamura H, Ishihara S, Haga H, Yasuda M, Yamazaki R, Shirato H, Kawaguchi H, Nishioka T
    • Journal Title

      Cell Structure and Function 34

      Pages: 86-96

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel function of transcription factor ATF5 : blockade of p53-dependent apoptosis induced by ionizing irradiation2009

    • Author(s)
      Nishioka T
    • Journal Title

      Cell Structure and Function 34

      Pages: 17-22

    • NAID

      40017160761

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clear cell adenocarcinoma of the uterine cervix arising fro m a background of cervical endometriosis2009

    • Author(s)
      Hiromura T
    • Journal Title

      British Journal of Radiology 82

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Surgical complications of salvage total laryngectomy following concurrent chemoradiotherapy2008

    • Author(s)
      Furuta Y
    • Journal Title

      International Journal of Clinical Oncology 13

      Pages: 521-7

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Matrix Metalloproteinases Are Up-regulated In Sub-clones That Survived 10Gy Irradiation : A Possible Role Of Hypoxic-inducible Factor-alpha (HIF1a)2010

    • Author(s)
      Takeshi Nishioka
    • Organizer
      2010 Annual meeting of American Society of Radiation Oncology Biology Physics
    • Place of Presentation
      San Diego USA
    • Year and Date
      2010-11-02
    • Related Report
      2010 Final Research Report
  • [Presentation] Increased Invasiveness And Non-spheroid Morphology Change Of Human Lung Adenocarcinoma Cells That Survived 10gy Irradiation2009

    • Author(s)
      Takeshi Nishioka
    • Organizer
      Annual meeting of American Society of Therapeutic Radiology Oncology Biology Physics
    • Place of Presentation
      Chicago、America
    • Year and Date
      2009-11-02
    • Related Report
      2009 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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