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Radiosensitization based on intracellular redox control in cancer stem cells

Research Project

Project/Area Number 15H04904
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), 名誉教授 (40143937)

Co-Investigator(Kenkyū-buntansha) 田渕 圭章  富山大学, 研究推進機構 研究推進総合支援センター, 教授 (20322109)
松谷 裕二  富山大学, 大学院医学薬学研究部(薬学), 教授 (50255858)
小川 良平  富山大学, 大学院医学薬学研究部(医学), 准教授 (60334736)
趙 慶利  富山大学, 大学院医学薬学研究部(医学), 助教 (90313593)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2015: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywordsスルファサラジン / 幹細胞 / 放射線 / 放射線治療 / 活性酸素 / 温熱 / 大気圧プラズマ / 酸化ストレス / 細胞死 / がん幹細胞 / グルタチオン / 過酸化水素
Outline of Final Research Achievements

Sulfasalazine (SSZ) is an inhibitor of the cystine-glutamate antiporter known to reduce intracellular glutathione level and increase cellular oxidative stress, giving its anti-tumor potential. SSZ enhanced radiation-induced apoptosis in Molt-4 cells via the involvement of both intrinsic and extrinsic apoptotic pathways. In addition, to understand characteristics of stem cells, the immortalized human amniotic mesenchymal cells (iHAMs) and immortalized human amniotic epithelial cells (iHAEs) were utilized. To reveal response of these cells against X-rays and hydrogen peroxide, intracellular reactive oxygen species (ROS), cell viability, and apoptois were examined. Intracellular ROS level significantly increased in iHAMs after treatment, consequently cell viability also significantly decreased in iHAMs, but not in iHAEs. Radiation-induced apoptosis was also higher in iHAMs. Furthermore, proteins related to oxidative stress were also determined and detailed mechanism was discussed.

Report

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

    (35 results)

All 2017 2016 2015 Other

All Journal Article (17 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 17 results,  Open Access: 7 results,  Acknowledgement Compliant: 4 results) Presentation (13 results) (of which Int'l Joint Research: 7 results,  Invited: 4 results) Book (4 results) Remarks (1 results)

  • [Journal Article] Cold atmospheric helium plasma causes synergistic enhancement in cell death with hyperthermia and an additive enhancement with radiation2017

    • Author(s)
      Moniruzzaman Rohan, Qing-Li Zhao, Paras Jawaid, Keigo Takeda, Kenji Ishikawa, Masaru Hori, Kei Tomihara, Noguchi Kyo, Takashi Kondo, and Makoto Noguchi
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 11659-11659

    • DOI

      10.1038/s41598-017-11877-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 3-O-trans-p-coumaroyl-alphitolic acid, a triterpenoid from Zizyphus jujuba, leads to apoptotic cell death in human leukemia cells through reactive oxygen species production and activation of the unfolded protein response2017

    • Author(s)
      Mitsuhashi Y, Furusawa Y, Aradate T, Zhao QL, Moniruzzaman R, Kanamori M, Noguchi K, Kondo T
    • Journal Title

      PLoS One

      Volume: 12(8) Issue: 8 Pages: e0183712-e0183712

    • DOI

      10.1371/journal.pone.0183712

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Checkpoint kinase 2 is dispensable for regulation of the p53 response but is required for G2/M arrest and cell survival in cells with p53 defects under heat stress2017

    • Author(s)
      Furusawa Yukihiro、Yamanouchi Yuka、Iizumi Takashi、Zhao Qing-Li、Mitsuhashi Yohei、Morita Akinori、Enomoto Atushi、Tabuchi Yoshiaki、Kondo Takashi
    • Journal Title

      Apoptosis

      Volume: 22 Issue: 10 Pages: 1225-1234

    • DOI

      10.1007/s10495-017-1402-2

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhancement of hyperthermia-induced apoptosis by 5Z-7-oxozeaenol, a TAK1 inhibitor, in Molt-4 cells2017

    • Author(s)
      Li P, Zhao, Q-L, Jawaid P; Rehman MU, Ahmed K, Sakurai H, Kondo T
    • Journal Title

      Int J Hyperthermia

      Volume: 22 Issue: 4 Pages: 1-11

    • DOI

      10.1080/02656736.2017.1278629

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Overexpression of the anti-apoptotic protein BAG3 in human choroidal melanoma. A case report2017

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

      Oncol Lett

      Volume: 13(6) Issue: 6 Pages: 4169-4172

    • DOI

      10.3892/ol.2017.5958

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hyperthermia and radiation reduce the toxic side-effects of bufadienolides for cancer therapy2017

    • Author(s)
      Emam H, Refaat A, Jawaid P, Rehman MU, Li P, Zhao QL, Kondo T
    • Journal Title

      Oncol Lett

      Volume: 14(1) Issue: 1 Pages: 1035-1040

    • DOI

      10.3892/ol.2017.6256

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Potential hazards of fenvalerate in massive pollution influence the apoptosis sensitivity2017

    • Author(s)
      Cui Zheng-Guo、Jin Yu-Jie、Sun Lu、Zakki Shahbaz Ahmad、Li Meng-Ling、Feng Qian-Wen、Kondo Takashi、Ogawa Ryohei、Inadera Hidekuni
    • Journal Title

      Journal of Applied Toxicology

      Volume: 38 Issue: 2 Pages: 240-247

    • DOI

      10.1002/jat.3517

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparison of biological effects of modulated electro-hyperthermia and conventional heat treatment in human lymphoma U937 cells2016

    • Author(s)
      Andocs G, Rehman MU, Zhao QL, Tabuchi Y, Kanamori M, Kondo T
    • Journal Title

      Cell Death and Discovery

      Volume: 2 Issue: 1 Pages: 16039-16039

    • DOI

      10.1038/cddiscovery.2016.39

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Helium based cold atmospheric plasma-induced reactive oxygen species-mediated apoptotic pathway attenuated by platinum nanoparticles.2016

    • Author(s)
      Jawaid P, Rehman MU, Zhao QL, Takeda K, Ishikawa K, Hori M, Shimizu T, Kondo T:
    • Journal Title

      J. Cell Mol Med

      Volume: 20 Issue: 9 Pages: 1737-1748

    • DOI

      10.1111/jcmm.12880

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Low dose spiruchostatin-B, a potent histone deacetylase inhibitor enhances radiation-induced apoptosis in human lymphoma U937 cells via modulation of redox signaling2016

    • Author(s)
      Rehman MU, Jawaid P, Zhao QL, Li P, Narita K, Kato T, Shimizu T, Kondo T
    • Journal Title

      Free Radic Res

      Volume: 24 Issue: 6 Pages: 1-15

    • DOI

      10.3109/10715762.2015.1115029

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Gene network analysis of genes involved in enhancement of hyperthermia sensitivity by knockdown of BAG3 in human oral squamous cell carcinoma cells2016

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

      Int J Mol Med

      Volume: 38 Issue: 1 Pages: 236-242

    • DOI

      10.3892/ijmm.2016.2621

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comprehensive and computational analysis of genes in human umbilical vein endotherial cells responsive to X-irradiation2016

    • Author(s)
      Furusawa Y, Zhao QL,Hattori Y, Tabuchi Y, Iwasaki T, Nomura T, Kondo T
    • Journal Title

      Genomics Data

      Volume: 8 Pages: 126-130

    • DOI

      10.1016/j.gdata.2016.05.007

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dual effects of nanoparticles on radiation therapy: as radiosensitizers and radioprotectors2016

    • Author(s)
      Rehman MU, Jawaid P, Kondo T
    • Journal Title

      Radiation Environment and Medicine

      Volume: 5 Pages: 40-45

    • NAID

      40020835108

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of platinum nanoparticles on cell death induced by ultrasound in human lymphoma U937 cells2016

    • Author(s)
      Jawaid P, RehmanMU, Hassan MA, Zhao QL, Li P, Miyamoto Y, Misawa M, Ogawa R, Shimizu T, and Kondo T
    • Journal Title

      Ultrason Sonochem

      Volume: 31 Pages: 206-215

    • DOI

      10.1016/j.ultsonch.2015.12.013

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hyperthermia: an effective strategy to induce apoptosis in cancer cells2015

    • Author(s)
      Ahmed K, Tabuchi Y, and Kondo T
    • Journal Title

      Apoptosis

      Volume: 20 Issue: 11 Pages: 1411-1419

    • DOI

      10.1007/s10495-015-1168-3

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Roles of ROS and PKC-betaII in ionizing radiation-induced eNOS activation in human vascular endothelial cells.2015

    • Author(s)
      Sakata K, Kondo T, Mizuno N, Shoji M, Yasui H, Yamamori T, Inanami O, Yokoo H, Yoshimura N, Hattori Y.
    • Journal Title

      Vascular Pharmacology

      Volume: - Pages: 55-65

    • DOI

      10.1016/j.vph.2015.03.016

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cellular effects of low-intensity pulsed ultrasound and X-irradiation in combination in two human leukemia cell lines2015

    • Author(s)
      Buldakov MA, Hassan MA, Jawaid P, Cherdyntseva NV, Kondo T
    • Journal Title

      Ultrason Sonochem

      Volume: 23 Pages: 339-346

    • DOI

      10.1016/j.ultsonch.2014.08.018

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 酸化ストレス制御による細胞死増強2017

    • Author(s)
      近藤 隆
    • Organizer
      第19回癌治療増感研究シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 放射線および超音波誘発細胞死におよぼす白金および金ナノ粒子の影響2017

    • Author(s)
      近藤 隆,P. Jawaid,M. U. Rehman, 趙 慶利,小川良平,清水忠道,宮本有生,野口 京
    • Organizer
      第55回日本放射線腫瘍学会生物部会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Bicyclic depsipeptides, novel histone deacetylase inhibitors enhanced hyperthermia-induced apoptosis via HDAC inhibition and modulation of intracellular reactive oxygen species2017

    • Author(s)
      Rehman MU, Jawaid P, Zhao QL, Narita K, Katoh T, Noguchi K, Kondo T
    • Organizer
      第23回癌治療増感研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 放射線生物学への期待-他の物理的因子と比較して2017

    • Author(s)
      近藤 隆
    • Organizer
      平成29年度若手放射線生物学研究会専門研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] DNA損傷応答経路を標的とした温熱増感の可能性2017

    • Author(s)
      古澤之裕,飯泉天志,田渕圭章,近藤 隆
    • Organizer
      日本ハイパーサーミア学会第34回大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Comparative studies on enhancement of cell killing induced by ultrasound in the presence of platinum and go0ld nanoparticles2016

    • Author(s)
      Kondo T
    • Organizer
      5th Joint Meeting of the Acoustical Society of America and the Acoustical Society of Japan
    • Place of Presentation
      Honolulu
    • Year and Date
      2016-11-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Differential role of small sized gold nano-particles on X-irradiation and ultrasound induced cell death2016

    • Author(s)
      Jawaid P, Rehman MU, Zhao QL, Kondo T
    • Organizer
      23rd annual meeting of the society of redox biology and medicine, a joint meeting with society for free radical research international
    • Place of Presentation
      San Francisco
    • Year and Date
      2016-11-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Combination of cold atmospheric helium plasma and mild hyperthermia causes a synergistic enhancement in cell death mainly via up-regulation of intracellular reactive oxygen species2016

    • Author(s)
      Rehman MU, Moniruzzaman R, Zhao QL, Jawaid P, Kondo T
    • Organizer
      23rd annual meeting of the society of redox biology and medicine, a joint meeting with society for free radical research international
    • Place of Presentation
      San Francisco
    • Year and Date
      2016-11-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 物理的治療因子の整形外科治療への応用-放射線、温熱、超音波そしてプラズマ-2015

    • Author(s)
      近藤 隆
    • Organizer
      第30回日本整形外科学会基礎学術集会
    • Place of Presentation
      富山
    • Year and Date
      2015-10-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Spiruchostatin-B, potent histone deacetylase inhibitor enhances radio-sensitivity in human leukemia cells by Fas-mitochondria pathway2015

    • Author(s)
      Rehman MU, Jawaid P, Zhao QL, Narita K, Katoh T, Shimizu T, Kondo T
    • Organizer
      The 15th International Congress of Radiation Research
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The lysolipin I enhances radiation-induced apoptosis2015

    • Author(s)
      Zhao QL, Rehman MU, Igarashi Y, Kondo T
    • Organizer
      The 15th International Congress of Radiation Research
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dual effects of platinum nano-particles on cell death induced by X-irradiation and ultrasound in human lymphoma U937 cells2015

    • Author(s)
      Jawaid P, Rehman MU, Zhao QL, Li P, Miyamoto Y, Kondo T
    • Organizer
      The 15th International Congress of Radiation Research
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The mechanisms underlying irradiation-induced eNOS activation in human vascular endothelial cells2015

    • Author(s)
      Sakata K, Mizuno N, Kondo T, Yoshimura N, Hattori Y
    • Organizer
      The 15th International Congress of Radiation Research
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Book] Hyperthermic Oncology from Bench to Bedside2016

    • Author(s)
      Tabuchi Y, Ahmed K, Kondo T
    • Total Pages
      12
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Book] Sonochemistry and the Acoustic Bubble2015

    • Author(s)
      Kondo T
    • Total Pages
      23
    • Publisher
      Elsevier Inc
    • Related Report
      2015 Annual Research Report
  • [Book] Skin Aging and Photoaging: Physiology, Clinical Aspects and Emerging Therapies2015

    • Author(s)
      Rehman MU, Kondo T, Shimizu T
    • Total Pages
      15
    • Publisher
      Nova Science Publishers
    • Related Report
      2015 Annual Research Report
  • [Book] 放射線生物学2015

    • Author(s)
      近藤 隆
    • Total Pages
      8
    • Publisher
      近代出版
    • Related Report
      2015 Annual Research Report
  • [Remarks] 富山大学医学部放射線基礎医学講座

    • URL

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

    • Related Report
      2017 Annual Research Report

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

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