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Elucidation of Molecular Mechanism of Cell Death induced by Radiation, Hyperthermia and Ultrasound for Cancer Therapy

Research Project

Project/Area Number 22390229
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionUniversity of Toyama

Principal Investigator

KONDO Takashi  富山大学, 大学院・医学薬学研究部(医学), 教授 (40143937)

Co-Investigator(Kenkyū-buntansha) TABUCHI Yoshiaki  富山大学, 生命科学先端研究センター, 准教授 (20322109)
ZHAO Qing-li  富山大学, 大学院・医学薬学研究部(医学), 助教 (90313593)
TAKASAKI Ichro  富山大学, 生命科学先端研究センター, 助教 (00397176)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2011: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2010: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywords放射線腫瘍学 / 超音波治療学 / 温熱治療学 / ハイパーサーミア / アポトーシス / 放射線 / 超音波 / TAK1 / Chk1 / 遺伝子発現 / がん / 細胞死 / 治療
Research Abstract

Molecular mechanism of cell death induced by ionizing radiation, heat or ultrasound was examined. Stable knockdown of TAK1 caused increase in subG1 fraction and apoptosis induced by X-rays in HeLa cells. Inhibition of DNA-PK increased heat-induced apoptosis in HeLa cells and the knockdown of an identified gene, NR1D1, also enhanced apoptosis. For the cell death induced by ultrasound, cell death signal is modulated by the balance between p53 and Akt via ATM and DNA-PK and the pathway of DNA-PK/Akt is predominant in sonicated cells.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (35 results)

All 2013 2012 2011 2010 Other

All Journal Article (22 results) (of which Peer Reviewed: 22 results) Presentation (8 results) (of which Invited: 4 results) Book (3 results) Remarks (2 results)

  • [Journal Article] Utilization of microRNAs whose expression levels decrease in responseto X-ray irradiation for fine-tuning radiation-controlled gene regulation2013

    • Author(s)
      Morii A, Ogawa R, Watanabe A, Cui Z-G, Takasaki I, Doi T, Kondo T, FuseH
    • Journal Title

      Int J Mol Med (in press)

      Volume: 32 Issue: 1 Pages: 1360-1360

    • DOI

      10.3892/ijmm.2013.1360

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inactivation of DNA-dependent protein kinase promotes heat-induced apoptosis independently of heat-shock protein induction in human cancer cell lines2013

    • Author(s)
      Okazawa S, Furusawa Y, Kariya A,Hassan MA, Arai M, Hayashi R, TabuchiY, Kondo T, Tobe K
    • Journal Title

      PLos One

      Volume: 8(3) Issue: 3 Pages: e58325-e58325

    • DOI

      10.1371/journal.pone.0058325

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The combination of silencing BAG3 and inhibition of the JNK pathway enhances hyperthermia sensitivity in human oral squamous cell carcinoma cells2013

    • Author(s)
      Yunoki T, Kariya A, Kondo T, Hayashi A, and Tabuchi Y
    • Journal Title

      Cancer Lett(inpress)

      Volume: 335 Issue: 1 Pages: 49-49

    • DOI

      10.1016/j.canlet.2013.01.049

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] TGF-beta-activated kinase 1 promotes cell cycle arrest and cell survival of X-ray-irradiated HeLa cells dependent on p21 induction but independent of NF-kB, p38 MAPK and ERK phosphorylations2012

    • Author(s)
      Furusawa Y, Wei ZL, Sakurai H, Tabuchi Y, Li P, Zhao Q-L, Zhao, Nomura T, Saiki I, and Kondo T
    • Journal Title

      Radiat Res

      Volume: 177 Issue: 6 Pages: 766-774

    • DOI

      10.1667/rr2792.1

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of checkpoint kinase 1 abrogates G2/M checkpoint activation and promotes apoptosis under heat stress2012

    • Author(s)
      Furusawa Y, Iizumi T, Fujiwara Y, Zhao Q-L, Tabuchi Y, Nomura T, and Kondo T
    • Journal Title

      Apoptosis

      Volume: 17 Issue: 1 Pages: 102-112

    • DOI

      10.1007/s10495-011-0660-7

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of gene expression in human prostate cancer cells with artificially constructed promoters that are activated in response to ultrasound stimulation2012

    • Author(s)
      Ogawa R., A. Morii, A. Watanabe, Z. G. Cui, G. Kagiya, T. Kondo, N. Doi, L. B. Feril
    • Journal Title

      Ultrason Sonochem

      Volume: 20 Issue: 1 Pages: 460-467

    • DOI

      10.1016/j.ultsonch.2012.05.007

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mitochondria-Targeted Superoxide Dismutase (SOD2) Regulates Radiation Resistance and Radiation Stress Response in HeLa Cells2012

    • Author(s)
      Hosoki, A., S. Yonekura, Q-L. Zhao, Z-L. Wei, I. Takasaki, Y. Tabuchi, L-L. Wang, S. Hasuike, T. Nomura, A. Tachibana, K. Hashiguchi, S. Yonei, T. Kondo and Q-M. Zhang-Akiyama
    • Journal Title

      Journal of Radiation Research

      Volume: 53 Issue: 1 Pages: 58-71

    • DOI

      10.1269/jrr.11034

    • NAID

      10030023538

    • ISSN
      0449-3060, 1349-9157
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA double-strand breaks induced by cavitational mechanical effects of ultrasound in cancer cell lines2012

    • Author(s)
      Furusawa Y., Y. Fujiwara, P. Campbell, Q. L. Zhao, R. Ogawa, M. A. Hassan, Y. Tabuchi, I. Takasaki, A. Takahashi, T. Kondo
    • Journal Title

      PLoS ONE

      Volume: 7 Issue: 1 Pages: e29012-e29012

    • DOI

      10.1371/journal.pone.0029012

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ultrasound-induced new cellular mechanism involved in drug resistance2012

    • Author(s)
      Hassan MA, Furusawa Y, Minemura M, Rapoport N, Sugiyama T, and Kondo T
    • Journal Title

      PLoS One

      Volume: 7 Issue: 12 Pages: e48291-e48291

    • DOI

      10.1371/journal.pone.0048291

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of DNA-dependent protein kinase promotes ultrasound -induced cell death including apoptosis in human leukemia cells2012

    • Author(s)
      Furusawa Y, Fujiwara Y, Hassan MA, Tabuchi Y, Morita A, Enomoto A,and Kondo T
    • Journal Title

      Cancer Lett

      Volume: 322 Issue: 1 Pages: 107-112

    • DOI

      10.1016/j.canlet.2012.02.020

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ultrasound activates ataxia telangiectasia mutated- and Rad-3 related (ATR)-checkpoint kinase 1 (Chk1) pathway in human leukemia Jurkat cells2012

    • Author(s)
      Furusawa Y, Iizumi T, Fujiwara Y, Hassan MA, Tabuchi Y, Nomura T, and Kondo T
    • Journal Title

      Ultrason Sonochem

      Volume: 19 Issue: 6 Pages: 1246-1251

    • DOI

      10.1016/j.ultsonch.2012.04.003

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of gene expression in prostate cancer cells with an artificially constructed promoter responsive to radiation in vitro and in vivo2012

    • Author(s)
      Morii, A., R. Ogawa, A. Watanabe, S. Kakutani, K. Kume, T. Kondo and H. Fuse
    • Journal Title

      Gen Ther

      Volume: 19 Issue: 2 Pages: 219-227

    • DOI

      10.1038/gt.2011.89

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced gene transfection using calcium phosphate co-precipitates and low-intensity pulsed ultrasound2012

    • Author(s)
      Hassan MA, Ahmed IS, Campbell P, Kondo T
    • Journal Title

      Eur J Pharmaceut Sci

      Volume: 47 Pages: 768-773

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular mechanisms of apoptosis induction by 2-dodecylcyclobutane, a radiolytic product of palmitic acid, in human lymphomaU937 cells2012

    • Author(s)
      Yu D-Y
    • Journal Title

      Apoptosis

      Volume: 17 Issue: 6 Pages: 636-645

    • DOI

      10.1007/s10495-012-0698-1

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene networks related to the cell death elicited by hyperthermia2012

    • Author(s)
      Tabuchi Y
    • Journal Title

      Int J Mol Med

      Volume: 29 Pages: 380-386

    • DOI

      10.3892/ijmm.2011.862

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Apoptotic cell death by the novel natural compound, cinobufotalin2012

    • Author(s)
      Emam H
    • Journal Title

      Chem Biol Interact

      Volume: 199 Issue: 3 Pages: 154-160

    • DOI

      10.1016/j.cbi.2012.07.005

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hyperthermia enhances the effect of β-lapachone to cause γH2AX formation and cell death in human osteosarcoma cells2011

    • Author(s)
      Hori T., et al.
    • Journal Title

      Int J Hyperthermia

      Volume: 27 Pages: 53-62

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SOD/catalase mimetic platinum nanoparticles inhibit heat-induced apoptosis in human lymphoma U937 and HH cells2011

    • Author(s)
      Yoshihisa Y., et al.
    • Journal Title

      Free Radic.Res.

      Volume: 45 Issue: 3 Pages: 326-335

    • DOI

      10.3109/10715762.2010.532494

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Indetification of biological functions and gene networks regulated by heat stress in U937 human lymphoma cells2011

    • Author(s)
      Furusawa Y., et al.
    • Journal Title

      Int.J.Mol.Med.

      Volume: 28 Pages: 143-151

    • DOI

      10.3892/ijmm.2011.702

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of Ca^<2+> in ultrasound-elicited bioeffects : progress, perspectives and prospects.2010

    • Author(s)
      Hassan M.A., et al.
    • Journal Title

      Drug Discovery Today

      Volume: 15 Pages: 892-906

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ionizing radiation enhances Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-induced apoptosis through up-regulations of death receptor 4 (DR4) and death receptor 5 (DR5) in human osteosarcoma cells.2010

    • Author(s)
      Hori T., et al.
    • Journal Title

      J.Orthopadeic Res.

      Volume: 28 Pages: 739-745

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ultrasound-induced apoptosis in the presence of Sonazoid and associated alterations in gene expression levels : A ossible therapeutic application.2010

    • Author(s)
      Furusawa Y., et al.
    • Journal Title

      Cancer Lett.

      Volume: 288 Pages: 107-115

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Roles of intracellular oxidative stress in DNA Damage and apoptosis induced by different physical stressors; ionizing radiation, hyperthermia and ultrasound2012

    • Author(s)
      Kondo T, Hassan MA, Zhao QL, Ogawa R, Tabuchi Y, and Furusawa Y
    • Organizer
      28th RBC-NIRS International Symposium, Radiationassociated Repair Proteins and DNA Repair Network
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2012 Final Research Report
  • [Presentation] Roles of intracellular oxidative stress in the enhancement of hyperthermia-induced apoptosis. (ASHO award Lecture)2012

    • Author(s)
      Kondo T
    • Organizer
      The 11th International Congress of Hyperthermic Oncology (ICHO) & The 29th Japanese Congress of Thermal Medicine
    • Place of Presentation
      Kyoto
    • Related Report
      2012 Final Research Report
  • [Presentation] Roles of intracellular oxidative stress in the enhancement of hyperthermia-induced apoptosis.2012

    • Author(s)
      KondoT
    • Organizer
      The 11th International Congress of Hyperthermic Oncology (ICHO) & The 29th Japanese Congress of Thermal Medicine
    • Place of Presentation
      Kyoto
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Roles of intracellular oxidative stress in DNA Damage and apoptosis induced by different physical stressors; ionizing radiation, hyperthermia and ultrasound2012

    • Author(s)
      KondoT
    • Organizer
      28th RBC-NIRS International Symposium, Radiation-associated Repair Proteins and DNA Repair Network
    • Place of Presentation
      Kyoto
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Identification of genes responsive to mild hyperthermia in normal human fibroblastic cells2012

    • Author(s)
      Tabuchi Y
    • Organizer
      The 11th International Congress of Hyperthermic Oncology (ICHO) & The 29th Japanese Congress of Thermal Medicine
    • Place of Presentation
      Kyoto
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Global expression profiling of genes induced by heat stress. Symposium 9, Cell signaling and damage response2012

    • Author(s)
      Tabuchi Y
    • Organizer
      The 11th International Congress of Hyperthermic Oncology (ICHO) & The 29th Japanese Congress of Thermal Medicine
    • Place of Presentation
      Kyoto
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Knockdown of TGF-beta activated kinase 1 (TAK1) promotes cell death induced by ionizing radiation2011

    • Author(s)
      Kondo T., et al.
    • Organizer
      14th International Congress of Radiation Research
    • Place of Presentation
      Warsaw, Poland
    • Related Report
      2011 Annual Research Report
  • [Presentation] Molecular bioeffects of low-intensity ultrasound : DNA damage, apoptosis, and alterations in gene expression.2010

    • Author(s)
      Kondo T., et al.
    • Organizer
      The 2010 International Chemical Congress of Pacific Basin Societies
    • Place of Presentation
      Honolulu, USA
    • Year and Date
      2010-12-16
    • Related Report
      2010 Annual Research Report
  • [Book] 音響サイエンスシリーズ,7.音響バブルとソノケミストリー、第9章バイオ・医学への応用2012

    • Author(s)
      近藤 隆
    • Publisher
      コロナ社
    • Related Report
      2012 Annual Research Report
  • [Book] Chapter 12: Sonodynamic Therapy in Therapeutic Ultrasound: Mechanisms to Applications (Public Health in the 21st Century)2011

    • Author(s)
      Feril LB Jr., Tachibana K, Kondo T, and Campbell P
    • Publisher
      Editor, Frenkel V. 279-295, Nova Science Publishers, Inc
    • Related Report
      2012 Final Research Report
  • [Book] Ultrasound-induced DNA damage and signal transductions indicated by gamma H2AX2011

    • Author(s)
      Furusawa Y, Fijiwara Y, Zhao Q-L, Hassan MA, Ogawa R, Tabuchi Y, Takasaki I,Takahashi A, Ohnishi T, and Kondo T
    • Publisher
      10th International Symposium on Therapeutic Ultrasound (ISTU2010) Editors, Matsumoto Y, Crum LA, and ter Haar GR, 322-325, AIP Conf Proc 1359, American Institute of Physics
    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

      http://www.med.u-toyama.ac.jp/radsci/index.html

    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

      http://www.med.u-toyama.ac.jp/radsci/index.html

    • Related Report
      2010 Annual Research Report

URL: 

Published: 2010-08-23   Modified: 2019-07-29  

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