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Genome-wide Screening of Novel Genes Responsible for Tumor Radioresistance

Research Project

Project/Area Number 16K15576
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, 放射線生物研究センター, 教授 (80362531)

Co-Investigator(Kenkyū-buntansha) 吉村 通央  京都大学, 医学研究科, 講師 (40597936)
後藤 容子  京都大学, 医学研究科, 特定助教 (60755651)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsがん / 放射線 / 治療抵抗性 / 責任遺伝子 / スクリーニング / 抵抗性 / 原因遺伝子 / 遺伝学的スクリーニング / 放射線抵抗性
Outline of Final Research Achievements

Through a genetic screening experiment, we successfully identified novel genes which potentially induce radioresistance of cancer cells. Clonogenic cell survival assay with the use of their expression vector confirmed that some of the genes actually increase radioresistance of cancer cells. We revealed mechanisms of action of one of the genes; it increased the levels of an intracellular antioxidant, GSH, for radioresistance. IHC analysis for clinical tumor samples found positive correlation between the expression levels of the gene product and poor prognosis of cancer patients.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (50 results)

All 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (17 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 15 results,  Open Access: 11 results,  Acknowledgement Compliant: 3 results) Presentation (28 results) (of which Int'l Joint Research: 6 results,  Invited: 28 results) Book (1 results) Remarks (2 results)

  • [Int'l Joint Research] オックスフォード大学/インペリアルカレッジ・ロンドン(英国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] University of Oxford/Imperial College London(英国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] HIF-1 maintains a functional relationship between pancreatic cancer cells and stromal fibroblasts by upregulating expression and secretion of Sonic hedgehog2018

    • Author(s)
      Katagiri Tomohiro、Kobayashi Minoru、Yoshimura Michio、Morinibu Akiyo、Itasaka Satoshi、Hiraoka Masahiro、Harada Hiroshi
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 12 Pages: 10525-10535

    • DOI

      10.18632/oncotarget.24156

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulatory mechanisms of hypoxia-inducible factor 1 activity: Two decades of knowledge2018

    • Author(s)
      Koyasu Sho、Kobayashi Minoru、Goto Yoko、Hiraoka Masahiro、Harada Hiroshi
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 3 Pages: 560-571

    • DOI

      10.1111/cas.13483

    • NAID

      120006454672

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A circadian clock gene, PER2, activates HIF-1 as an effector molecule for recruitment of HIF-1α to promoter regions of its downstream genes2017

    • Author(s)
      Kobayashi Minoru、Morinibu Akiyo、Koyasu Sho、Goto Yoko、Hiraoka Masahiro、Harada Hiroshi
    • Journal Title

      The FEBS Journal

      Volume: 284 Issue: 22 Pages: 3804-3816

    • DOI

      10.1111/febs.14280

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The emerging roles of the ubiquitination/deubiquitination system in tumor radioresistance regarding DNA damage responses, cell cycle regulation, hypoxic responses, and antioxidant properties: Insight into the development of novel radiosensitizing strategies2017

    • Author(s)
      Goto Yoko、Koyasu Sho、Kobayashi Minoru、Harada Hiroshi
    • Journal Title

      Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis

      Volume: 803-805 Pages: 76-81

    • DOI

      10.1016/j.mrfmmm.2017.07.007

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] UCHL1-HIF-1 axis-mediated antioxidant property of cancer cells as a therapeutic target for radiosensitization2017

    • Author(s)
      Nakashima Ryota、Goto Yoko、Koyasu Sho、Kobayashi Minoru、Morinibu Akiyo、Yoshimura Michio、Hiraoka Masahiro、Hammond Ester M.、Harada Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 6879-6879

    • DOI

      10.1038/s41598-017-06605-1

    • NAID

      120006355750

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] pH-Responsive near-infrared fluorescent cyanine dyes for molecular imaging based on pH sensing2017

    • Author(s)
      Miki Koji、Kojima Kentaro、Oride Kazuaki、Harada Hiroshi、Morinibu Akiyo、Ohe Kouichi
    • Journal Title

      Chemical Communications

      Volume: 53 Issue: 55 Pages: 7792-7795

    • DOI

      10.1039/c7cc03035e

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HIF-1-mediated suppression of mitochondria electron transport chain function confers resistance to lidocaine-induced cell death2017

    • Author(s)
      Okamoto Akihisa、Sumi Chisato、Tanaka Hiromasa、Kusunoki Munenori、Iwai Teppei、Nishi Kenichiro、Matsuo Yoshiyuki、Harada Hiroshi、Takenaga Keizo、Bono Hidemasa、Hirota Kiichi
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 3816-3816

    • DOI

      10.1038/s41598-017-03980-7

    • NAID

      120006364104

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HIF-1とがんの代謝2017

    • Author(s)
      原田浩
    • Journal Title

      実験医学

      Volume: 35 Pages: 1586-1592

    • Related Report
      2017 Annual Research Report
  • [Journal Article] がん特異的グルコース代謝経路による放射線抵抗性と放射線治療増感への展開2017

    • Author(s)
      後藤容子、中島良太、原田浩
    • Journal Title

      放射線生物研究

      Volume: 52 Pages: 277-290

    • NAID

      40021362518

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Hypoxia-inducible factor 1 promotes chemoresistance of lung cancer by inducing carbonic anhydrase IX espression2017

    • Author(s)
      Sowa T, Menju T, Chen-Yoshikawa TF, Takahashi K, Nishikawa S, Nakanishi T, Shikuma K, Motoyama H, Hijiya K, Aoyama A, Sato T, Sonobe M, Harada H, Date H
    • Journal Title

      Cancer Medicine

      Volume: 6 Issue: 1 Pages: 288-297

    • DOI

      10.1002/cam4.991

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cigarette smoke reversibly activates hypoxia-inducible factor 1 in a reactive oxygen species-dependent manner2016

    • Author(s)
      Daijo H, Hoshino Y, Kai S, Suzuki K, Nishi K, Matsuo Y, Harada H, Hirota K
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 34424-34424

    • DOI

      10.1038/srep34424

    • NAID

      120005850269

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] LY6E: a conductor of malignant tumor growth through modulation of the PTEN/PI3K/Akt/HIF-1 axis2016

    • Author(s)
      Harada H et al.
    • Journal Title

      Oncotarget

      Volume: 7(40) Issue: 40 Pages: 65837-65848

    • DOI

      10.18632/oncotarget.11670

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] VHL-deficient renal cancer cells gain resistance to mitochondria-activating apoptosis inducers by activating AKT through the IGF1R-PI3K pathway2016

    • Author(s)
      Yamaguchi R, Harada H, Hirota K
    • Journal Title

      Tumor Biology

      Volume: 37 Issue: 10 Pages: 13295-13306

    • DOI

      10.1007/s13277-016-5260-2

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [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
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Potent anti-tutor effects of EGFR-targeted hybrid peptide on mice bearing liver metastases2016

    • Author(s)
      Gaowa A, Horibe T, Kohno M, Harada H, Hiraoka M, Kawakami K
    • Journal Title

      Clin Exp Metastasis

      Volume: 33 Issue: 1 Pages: 87-95

    • DOI

      10.1007/s10585-015-9760-z

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [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
      2016 Research-status 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
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 照準を合わせろ! がんに対する放射線治療の現状と課題2018

    • Author(s)
      原田浩
    • Organizer
      第13回京都大学附置研究所・センターシンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Hypoxic Microenvironments in Malignant Solid Tumors2018

    • Author(s)
      Harada H
    • Organizer
      International Mini-symposium on Organs under Stress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] がん・低酸素・HIF-12018

    • Author(s)
      原田浩
    • Organizer
      国立京都医療センター臨床研究センター特別講演会.
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 腫瘍内微小環境と放射線感受性・抵抗性2018

    • Author(s)
      原田浩
    • Organizer
      JASTRO第8回放射線生物学セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 細胞の低酸素応答を担う新規遺伝子の作用機序と機能2017

    • Author(s)
      原田浩
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] がんに対する放射線治療の現状・課題・私たちの取り組み;低酸素バイオロジーの視点から2017

    • Author(s)
      原田浩
    • Organizer
      富山大学医歯薬総合研究科特別講演会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] How can we overcome tumor radioresistance; lessons from hypoxia biology2017

    • Author(s)
      Harada H
    • Organizer
      The 1st isRTB
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] がんに対する放射線治療の現状と課題2017

    • Author(s)
      原田浩
    • Organizer
      知の拠点セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Radioresistance of Cancer Cells; Lessons from HIF-1 Biology2017

    • Author(s)
      原田浩
    • Organizer
      放射線生物学セミナー in Gifu
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] HIF-1バイオロジーで迫るがんの放射線抵抗性2017

    • Author(s)
      原田浩
    • Organizer
      若手放射線生物研究専門研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] HIF-1の生物学:基礎研究から創薬研究への展開2017

    • Author(s)
      原田浩
    • Organizer
      新規分子標的治療薬創薬に向けた大学発ベンチャー基盤の確立シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] がんの悪性進展と治療抵抗性を担うHIF-1を中心とする遺伝子ネットワーク2017

    • Author(s)
      原田浩
    • Organizer
      第5回低酸素研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] がん細胞のグルコース代謝2017

    • Author(s)
      原田浩
    • Organizer
      第19回京都大学大学院生命科学研究科シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Tumor hypoxia; an imaging and therapeutic target of interest for innovative radiation therapy2017

    • Author(s)
      Harada H
    • Organizer
      The 3rd Bordeaux-Kyoto Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 悪性固形腫瘍内の低酸素環境 -放射線生物学の視点から-2017

    • Author(s)
      原田浩
    • Organizer
      日本放射線腫瘍学会 第46回 放射線による制癌シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 腫瘍の微小環境と放射線感受性2017

    • Author(s)
      原田浩
    • Organizer
      日本放射線腫瘍学会 第7回 放射線生物学セミナー
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 現代生物学が放射線治療に指し示すもの2017

    • Author(s)
      原田浩
    • Organizer
      第15回 九州放射線治療システム研究会
    • Place of Presentation
      福岡
    • Related Report
      2016 Research-status Report
    • 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2017

    • Author(s)
      原田浩
    • Organizer
      日本がん分子標的治療学会 第12回トランスレーショナルリサーチワークショップ
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 生物研究の方向性; 放射線腫瘍学における生物研究2016

    • Author(s)
      原田浩
    • Organizer
      日本放射線腫瘍学会第29回学術大会
    • Place of Presentation
      京都
    • Year and Date
      2016-11-25
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] HIF-1を中心とする活性酸素ストレス応答の分子基盤と機能2016

    • Author(s)
      原田浩
    • Organizer
      日本放射線影響学会第59回大会
    • Place of Presentation
      広島
    • Year and Date
      2016-10-26
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Function of the UCHL1-HIF-1 Axis in Distant Metastasis and Radioresistance of Cancer Cells2016

    • Author(s)
      Hiroshi Harada
    • Organizer
      International Symposium of Radiation Biology Center, Kyoto University 2016
    • Place of Presentation
      Kyoto
    • Year and Date
      2016-09-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 放射線生物学・最近の話題 -低酸素とがん幹細胞-2016

    • Author(s)
      原田浩
    • Organizer
      第18回 日本放射線腫瘍学会(JASTRO)夏季セミナー
    • Place of Presentation
      名古屋
    • Year and Date
      2016-08-06
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Radioresistance of Cancer Cells; Lessons from HIF-1 Biology2016

    • Author(s)
      Hiroshi Harada
    • Organizer
      Annual Meeting of Association for Radiation Research 2016
    • Place of Presentation
      Leicester, UK
    • Year and Date
      2016-06-27
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Tumor Hypoxia; a Potent Inducer of Malignant Phenotypes and Radioresistance of Cancer Cells2016

    • Author(s)
      Hiroshi Harada
    • Organizer
      The 2nd KU RBC-CEA Joint Workshop
    • Place of Presentation
      Kyoto
    • Year and Date
      2016-04-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] がんの悪性化と治療抵抗性を左右する「腫瘍内微小環境」2016

    • Author(s)
      原田浩
    • Organizer
      第77回京都大学丸の内セミナー
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 悪性固形腫瘍内の微小環境と放射線抵抗性2016

    • Author(s)
      原田浩
    • Organizer
      第124回 熊本放射線腫瘍研究会
    • Place of Presentation
      熊本
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] がん・低酸素・HIF-12016

    • Author(s)
      原田浩
    • Organizer
      第27回 Forum in Dojin
    • Place of Presentation
      熊本
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] がん細胞の糖代謝経路と放射線抵抗性のクロストーク2016

    • Author(s)
      原田浩
    • Organizer
      第45回放射線による制癌シンポジウム
    • Place of Presentation
      大阪
    • Related Report
      2016 Research-status Report
    • Invited
  • [Book] 放射線医科学2016

    • Author(s)
      原田浩
    • Total Pages
      189
    • Publisher
      医療科学社
    • Related Report
      2016 Research-status Report
  • [Remarks] 京都大学放射線生物研究センターがん細胞生物学分野HP

    • URL

      http://www.rbc.kyoto-u.ac.jp/cancer_biology/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 京都大学放射線生物研究センターがん細胞生物学分野ホームページ

    • URL

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

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2022-06-16  

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