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Spatiotemporal analyses of the dynamics of hypoxic tumor cells for the optimization of fractionated radiation therapy for cancers

Research Project

Project/Area Number 26670558
Research Category

Grant-in-Aid for Challenging Exploratory Research

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

Principal Investigator

Harada Hiroshi  京都大学, 白眉センター, 准教授 (80362531)

Co-Investigator(Kenkyū-buntansha) Yoshimura Michio  京都大学, 大学院医学研究科, 助教 (40597936)
KOBAYASHI Minoru  京都大学, 大学院医学研究科, 研究員 (40644894)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsがん / 放射線治療 / 分割照射 / 腫瘍内低酸素 / HIF-1 / 放射線治療抵抗性 / 低酸素 / 細胞動態
Outline of Final Research Achievements

In the present study, we exploited a sophisticated strategy which enabled us to tag hypoxic cells with luciferase protein in tumor xenograft by using the hypoxia-responsive transcription factor-dependent Cre-loxP system, and performed spatiotemporal analyses about the dynamics of cancer cells in intratumoral hypoxic regions. What we found is that, 24 hours after hypoxic cells were tagged with luciferase protein in the regions 70-85 micrometers distant regions from tumor blood vessels, the cells were located in 85-100 micrometers from vessels. In the following day (48 hours after the tagging), the cells were detected in necrotic regions located more than 100 micrometer from vessels. These results support an idea that the interval of fractionated radiation therapy for cancer is about 24 hours.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (35 results)

All 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 14 results,  Open Access: 8 results,  Acknowledgement Compliant: 4 results) Presentation (16 results) (of which Int'l Joint Research: 2 results,  Invited: 16 results) Remarks (4 results)

  • [Int'l Joint Research] University of Oxford(英国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Hypoxia-inducible factor 1-mediated characteristic features of cancer cells for tumor radiaresistance.2016

    • Author(s)
      *Harada H.
    • Journal Title

      J Radiat Res

      Volume: 印刷中 Issue: S1 Pages: 99-99

    • DOI

      10.1093/jrr/rrw012

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Evaluation of Tumor-associated Stroma and Its Relationship with Tumor Hypoxia Using Dynamic Contrast-enhanced CT and 18F Misonidazole PET in Murine Tumor Models.2016

    • Author(s)
      Koyasu, S., Tsuji, Y., Harada, H., Nakamoto, Y., Nobashi, T., Kimura, H., Sano, K., Koizumi, K., Hamaji, M., Togashi, K.
    • Journal Title

      Radiology.

      Volume: 278 Issue: 3 Pages: 734-41

    • DOI

      10.1148/radiol.2015150416

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] H3K9me3 facilitates hypoxia-induced p53-dependent apoptosis through repression of APAK.2016

    • Author(s)
      Olcina MM, Leszczynska K, Senra JM, Isa N, Harada H, Hammond EM.
    • Journal Title

      Oncogene

      Volume: 35 Issue: 6 Pages: 793-799

    • DOI

      10.1038/onc.2015.134

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [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 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A novel method to visually determine the intracellular pH of xenografted tumor in vivo by utilizing fluorescent protein as an indicator.2015

    • Author(s)
      Shotaro Tanaka
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 464 Issue: 4 Pages: 1151-1156

    • DOI

      10.1016/j.bbrc.2015.07.095

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1alpha2015

    • Author(s)
      Goto Y, Zeng L, YeomCJ, Zhu Y, Morinibu A, Shinoyam K, Kobayashi M, Hirota K, Itasaka S, Yoshimura M, Tanimoto K, Sowa T, Menju T, Sonobe M, Kakeya H, Toi M, Date H, Hammond EM, Hiraoka M, Harada H.
    • Journal Title

      Nat Commun

      Volume: 6 Issue: 1 Pages: 1-10

    • DOI

      10.1038/ncomms7153

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] H3K9me3 facilitates hypoxia-induced p53-dependent apoptosis through repression of APAK.2015

    • Author(s)
      Olcina MM, Leszczynska K, Senra JM, Isa N, Harada H, Hammond EM.
    • Journal Title

      Oncogene

      Volume: in press

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis of Biocompatible Polysaccharide Analogues and Their Application to In Vivo Optical Tumor Imaging.2015

    • Author(s)
      Miki K, Kimura A, Inoue T, Matsuoka H, Harada H, Hiraoka M, Ohe K
    • Journal Title

      Bull Chem Soc Jpn.

      Volume: in press

    • NAID

      130005075674

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Aberrant IDH3α expression promotes malignant tumor growth by inducing HIF-1-mediated metabolic reprogramming and angiogenesis.2014

    • Author(s)
      Zeng L, Morinibu A, Kobayashi M, Zhu Y, Wang X, Goto Y, Yeom CJ, Zhao T,Hirota K, Shinomiya K, Itasaka S, Yoshimura M, Guo G, Hammond EM, Hiraoka M, Harada H.
    • Journal Title

      Oncogene

      Volume: epub Issue: 36 Pages: 4758-4766

    • DOI

      10.1038/onc.2014.411

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Near-infraredfluorescence imaging of cancer mediated by tumor hypoxia and HIF1α/OATPs signaling axis.2014

    • Author(s)
      Wu JB, Shao C, Li X, Shi C, Li Q, Hu P, Chen YT, Dou X, Sahu D, Li W, Harada H, Zhang Y, Wang R, Zhau HE, Chung LW.
    • Journal Title

      Biomaterials

      Volume: 35 Issue: 28 Pages: 8175-8185

    • DOI

      10.1016/j.biomaterials.2014.05.073

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sonication-Induced Formation of Size-Controlled Self-Assemblies of Amphiphilic Janus-Type Polymers as Optical Tumor-Imaging Agents2014

    • Author(s)
      K. Miki, H. Hashimoto, T. Inoue, H. Matsuoka, H. Harada, M. Hiraoka, K. Ohe
    • Journal Title

      Small

      Volume: 10 Issue: 15 Pages: 3119-3130

    • DOI

      10.1002/smll.201400358

    • NAID

      120005657907

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Plastic induction of CD133AC133-positive cells in the microenvironment of glioblastoma spheroid.2014

    • Author(s)
      Ohnishi K, Tani T, Bando S, Kubota N, Fujii Y, Hatano O, Harada H.
    • Journal Title

      Int J Oncol.

      Volume: 45 Issue: 2 Pages: 581-586

    • DOI

      10.3892/ijo.2014.2483

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] HIF-1-mediated metabolic reprogramming reduces ROS levels and facilitates the metastatic colonization of cancers in lungs.2014

    • Author(s)
      1. Zhao T, Zhu Y, Morinibu A, Kobayashi M, Shinomiya K, Itasaka S, Yoshimura M, Guo G, Hiraoka M, Harada H.
    • Journal Title

      Scientific Reports

      Volume: 4.3793 Issue: 1 Pages: 1-7

    • DOI

      10.1038/srep03793

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination of hybrid peptide with biodegradable gelatin hydrogel for controlled release and enhancement of anti-tumor activity in vivo.2014

    • Author(s)
      Gaowa A,(他7名)
    • Journal Title

      Journal of Controlled Release

      Volume: 176 Pages: 1-7

    • DOI

      10.1016/j.jconrel.2013.12.021

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] がん細胞の糖代謝経路リプログラミングと放射線抵抗性2016

    • Author(s)
      原田浩
    • Organizer
      第18回国際癌治療増感研究シンポジウム
    • Place of Presentation
      奈良
    • Year and Date
      2016-02-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Importance of Hypoxic Niche; Lessons from Hypoxia and Cancer Biology.2015

    • Author(s)
      原田浩
    • Organizer
      BMB2015
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Molecular Biology for the Advancement of Cancer Radiotherapy; in the Past and the Future.2015

    • Author(s)
      原田浩
    • Organizer
      日本放射線腫瘍学会 第28回学術大会
    • Place of Presentation
      群馬
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Tumor Hypoxia, a Potent Inducer of Malignant Phenotypes of Cancer Cells.2015

    • Author(s)
      Hiroshi Harada
    • Organizer
      2nd IFOM-Kyoto University Joint International Symposium
    • Place of Presentation
      京都
    • Year and Date
      2015-10-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] IDH3-HIF-1経路によるがん細胞の糖代謝リプログラミング.2015

    • Author(s)
      原田浩
    • Organizer
      第3回癌と代謝研究会
    • Place of Presentation
      金沢
    • Year and Date
      2015-07-16
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 低酸素バイオロジーに基づく放射線治療の新展開2015

    • Author(s)
      原田浩
    • Organizer
      日本医学放射線学会(JRS)中四国地方会 放射線治療懇話会 特別講演
    • Place of Presentation
      山口
    • Year and Date
      2015-06-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 放射線腫瘍学の視点でみる「がん幹細胞」2015

    • Author(s)
      原田浩
    • Organizer
      広島大学病院放射線治療講演会
    • Place of Presentation
      広島
    • Year and Date
      2015-06-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 低酸素バイオロジー研究に於けるデータベースの活用例2015

    • Author(s)
      原田浩
    • Organizer
      第13回 がんとハイポキシア研究会
    • Place of Presentation
      三島
    • Year and Date
      2015-06-07
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Tumor Hypoxia and Radioresistance.2015

    • Author(s)
      Hiroshi Harada
    • Organizer
      The 15th International Congress for Radiation Research (ICRR2015)
    • Place of Presentation
      京都
    • Year and Date
      2015-05-27
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] がん幹細胞と腫瘍内低酸素 -癌の診断と治療における重要性と展望-2015

    • Author(s)
      原田浩
    • Organizer
      第74回 日本医学放射線学会
    • Place of Presentation
      横浜
    • Year and Date
      2015-04-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 腫瘍内低酸素領域・HIF-1活性を診る意義 -低酸素バイオロジー研究で明らかになったがんの悪性形質獲得メカニズム-.2015

    • Author(s)
      原田浩, 平岡真寛
    • Organizer
      第17回国際癌治療増感シンポジウム
    • Place of Presentation
      奈良
    • Year and Date
      2015-02-06 – 2015-02-07
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] がんの微小環境研究を通して同定された新たな治療標的2015

    • Author(s)
      原田浩, 平岡真寛
    • Organizer
      第3回国際先端生物学・医学・工学会議
    • Place of Presentation
      名古屋
    • Year and Date
      2015-01-15 – 2015-01-16
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] UCHL1 provides novel diagnostic and antimetastatic strategy due to its deubiquitinating effect on HIF-1alpha.2014

    • Author(s)
      Harada H, Hiraoka M
    • Organizer
      Hypoxia Meeting, Oxford university
    • Place of Presentation
      Oxford, UK
    • Year and Date
      2014-07-04
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] IDH3によるがんの代謝リプログラミング機構の解明と新たな治療法確立への展開2014

    • Author(s)
      原田浩, 平岡真寛
    • Organizer
      第18回日本がん分子標的治療学会学術総会
    • Place of Presentation
      仙台
    • Year and Date
      2014-06-25 – 2014-06-27
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] HIF-1 as a Rational Target for Cancer Therapy.2014

    • Author(s)
      Harada H, Hiraoka M
    • Organizer
      International Symposium at Oxford Institute for Radiation Oncology
    • Place of Presentation
      Oxford, UK
    • Year and Date
      2014-05-29
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Importance of HIF-1 in Radiation Oncology.2014

    • Author(s)
      Harada H, Hiraoka M
    • Organizer
      The University of Oxford. Gray Institute for Radiation Oncology & Biology Seminar.
    • Place of Presentation
      Oxford, UK
    • Year and Date
      2014-04-07
    • Related Report
      2014 Research-status Report
    • Invited
  • [Remarks] 京都大学 放射線生物研究センター 原田研究室 ホームページ

    • URL

      http://radiotherapy.kuhp.kyoto-u.ac.jp/biology/index.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 京都大学大学院 医学研究科 放射線腫瘍学・画像応用治療学ホームページ

    • URL

      http://radiotherapy.kuhp.kyoto-u.ac.jp/biology/

    • Related Report
      2014 Research-status Report
  • [Remarks] Nature Communications誌に掲載された研究成果のプレスリリース(京大ホームページ)

    • URL

      http://www.kyoto-u.ac.jp/ja/research/research_results/2014/150113_1.html

    • Related Report
      2014 Research-status Report
  • [Remarks] Nature Communications誌に掲載された論文が、「注目の論文」にて紹介されたページ

    • URL

      http://www.natureasia.com/ja-jp/ncomms/abstracts/61434

    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2022-01-31  

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