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Genome-wide screening of blood markers for hypoxic cancer cells within malignant solid tumors

Research Project

Project/Area Number 21K19445
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 52:General internal medicine and related fields
Research InstitutionKyoto University

Principal Investigator

Harada Hiroshi  京都大学, 生命科学研究科, 教授 (80362531)

Co-Investigator(Kenkyū-buntansha) 小林 稔  京都大学, 生命科学研究科, 特定助教 (40644894)
Project Period (FY) 2021-07-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Keywordsがん / 微小環境 / 低酸素 / マーカー / が
Outline of Research at the Start

悪性固形腫瘍(がん)の内部には、血管から十分な酸素が供給されない領域が存在する。そこに巣食う低酸素がん細胞には抗がん剤や放射線治療が効きにくいことから、低酸素がん細胞を多く含む腫瘍を患っている患者を選別し、適切な医療を提供する必要がある。本研究では、がん患者の血液に含まれる成分によって低酸素がん細胞の量を簡便にモニターする手法を開発し、個別化医療の実現に繋げることを目指す。

Outline of Final Research Achievements

The oxygen environment in solid tumors is heterogeneous, with hypoxic regions that do not receive sufficient oxygen from blood vessels existing in areas 70 to 100 microns away from the vessels. Since cancer cells in this region have acquired resistance to radiotherapy, it is urgent to establish a simple and accurate method to monitor the amount of hypoxic regions in different tumors in different patients in order to realize personalized medicine for cancer patients.
As a result of searching for proteins expressed and secreted by hypoxia-stimulated cancer cells, four proteins including SPINK1, which we had already discovered, were identified. By selecting cases in which all four genes are highly expressed, we confirmed the possibility of monitoring tumor hypoxic fractions with high accuracy.

Academic Significance and Societal Importance of the Research Achievements

本研究で見出した4遺伝子の発現・分泌レベルを基に、腫瘍低酸素を高精度に予測するシステムの確立できると期待される。そうしてできた手法をがん患者に適用することによって、癌患者に対する個別化医療が実現されることが期待される。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (26 results)

All 2023 2022 2021 Other

All Int'l Joint Research (2 results) Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (14 results) (of which Int'l Joint Research: 4 results,  Invited: 10 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

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

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] University of Oxford(英国)

    • Related Report
      2021 Research-status Report
  • [Journal Article] ZBTB2 links p53 deficiency to HIF-1-mediated hypoxia signaling to promote cancer aggressiveness2022

    • Author(s)
      Koyasu Sho、Horita Shoichiro、Saito Keisuke、Kobayashi Minoru、Ishikita Hiroshi、Chow Christalle CT、Kambe Gouki、Nishikawa Shigeto、Menju Toshi、Morinibu Akiyo、Okochi Yasushi、Tabuchi Yoshiaki、Onodera Yasuhito、Takeda Norihiko、Date Hiroshi、Semenza Gregg L、Hammond Ester M、Harada Hiroshi
    • Journal Title

      EMBO reports

      Volume: 24 Issue: 1 Pages: 54042-54042

    • DOI

      10.15252/embr.202154042

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 放射線による細胞死と組織障害2022

    • Author(s)
      百海享洲、武内智史、王美惠、宮長真広、嶋貫悠、小林稔、原田浩
    • Journal Title

      医学のあゆみ

      Volume: 283 Pages: 23445-23450

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Proteolysis of a histone acetyl reader, ATAD2, induces chemoresistance of cancer cells under severe hypoxia by inhibiting cell cycle progression in S phase2022

    • Author(s)
      Haitani Takao、Kobayashi Minoru、Koyasu Sho、Akamatsu Shusuke、Suwa Tatsuya、Onodera Yasuhito、Nam Jin-Min、Nguyen Phuong Thi Lien、Menju Toshi、Date Hiroshi、Ogawa Osamu、Harada Hiroshi
    • Journal Title

      Cancer Letters

      Volume: 528 Pages: 76-84

    • DOI

      10.1016/j.canlet.2021.12.028

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tumor microenvironment and radioresistance.2021

    • Author(s)
      Suwa T, Kobayashi M, Nam JM, Harada H.
    • Journal Title

      Exp Mol Med.

      Volume: 53 Issue: 6 Pages: 1029-1029

    • DOI

      10.1038/s12276-021-00640-9

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An Overview of the Recent Development of Anticancer Agents Targeting the HIF-1 Transcription Factor2021

    • Author(s)
      Shirai Y, Chow CCT, Kambe G, Suwa T, Kobayashi M, Takahashi I, Harada H, Nam JM.
    • Journal Title

      Cancers

      Volume: 13 Issue: 11 Pages: 2813-2813

    • DOI

      10.3390/cancers13112813

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SPINK1 as a plasma marker for tumor hypoxia and a therapeutic target for radiosensitization.2021

    • Author(s)
      Suwa T, Kobayashi M, Shirai Y, Nam JM, Tabuchi Y, Takeda N, Akamatsu S, Ogawa O, Mizowaki T, Hammond EM, Harada H.
    • Journal Title

      JCI Insight.

      Volume: 6 Issue: 21

    • DOI

      10.1172/jci.insight.148135

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Hypoxic tumor cells: their dynamics during tumor growth and involvement in recurrence after radiation therapy2023

    • Author(s)
      Hiroshi HARADA
    • Organizer
      Sussex-Japan Genome Stability Meeting
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Crosstalk between cellular hypoxia signaling and DNA damage response mediated by a HIF-1 activator, ZBTB22023

    • Author(s)
      Gouki KAMBE, Minoru KOBAYASHI, Sho KOYASU, Hiroshi HARADA
    • Organizer
      ATW2023
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] がん抑制機構と低酸素応答機構をつなぐ新規遺伝子の同定と活用2022

    • Author(s)
      原田浩
    • Organizer
      第27回癌治療増感研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 血漿内SPINK1濃度を指標にした腫瘍内低酸素分画のモニタリング2022

    • Author(s)
      原田浩、諏訪達也
    • Organizer
      第59回JASTRO生物部会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 固形腫瘍内の不均一な酸素環境におけるがん細胞の動態と転移2022

    • Author(s)
      原田浩
    • Organizer
      第31回 日本がん転移学会学術集会・総会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 酸素生物学で迫るがん細胞の素顔2022

    • Author(s)
      原田浩
    • Organizer
      名古屋大学大学院創薬科学研究科 第154回創薬科学セミナー
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Radioresistance of hypoxic tumor cells; lessons from hypoxia and HIF-1 biology2022

    • Author(s)
      Hiroshi HARADA
    • Organizer
      The 5th Asian Congress of Radiation Research
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Tumor Hypoxic Fraction (THF)を予測する血漿バイオマーカーSPINK12022

    • Author(s)
      諏訪達也、小林稔、白井友香理、武田憲彦、溝脇尚志、原田浩
    • Organizer
      がんとハイポキシア研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Radioresistance of Hypoxic Tumor Cells2022

    • Author(s)
      Hiroshi HARADA
    • Organizer
      The 13th isDDRHD-2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 酸素生物学と放射線腫瘍学の接点2021

    • Author(s)
      原田浩
    • Organizer
      日本量子医科学会第1回学術総会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 高線量放射線照射後の腫瘍内酸素環境の変化に基づく分割照射法の再考2021

    • Author(s)
      原田浩
    • Organizer
      第34回日本放射線腫瘍学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] HIFシグナルが加速する悪性固形腫瘍内の細胞社会ダイバーシティー2021

    • Author(s)
      原田浩
    • Organizer
      第94回日本生化学学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 泌タンパク質 SPINK1 を活用した腫瘍内低酸素のモニタリングと放射線増感2021

    • Author(s)
      諏訪達也
    • Organizer
      低酸素研究会2021
    • Related Report
      2021 Research-status Report
  • [Presentation] 低酸素バイオロジーの視点で見るハイパーサーミアによる放射線増感2021

    • Author(s)
      原田浩
    • Organizer
      第38回日本ハイパーサーミア学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Remarks] 京都大学大学院生命科学研究科がん細胞生物学分野ホームページ

    • URL

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

    • Related Report
      2022 Annual Research Report
  • [Remarks] 京都大学大学院生命科学研究科がん細胞生物学分野ホームページ

    • URL

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

    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] 低酸素バイオマーカー及びその利用2022

    • Inventor(s)
      諏訪達也、小林稔、原田浩
    • Industrial Property Rights Holder
      諏訪達也、小林稔、原田浩
    • Industrial Property Rights Type
      特許
    • Filing Date
      2022
    • Related Report
      2022 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 低酸素バイオマーカー及びその利用2021

    • Inventor(s)
      諏訪達也、小林稔、原田浩
    • Industrial Property Rights Holder
      諏訪達也、小林稔、原田浩
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-108196
    • Filing Date
      2021
    • Related Report
      2021 Research-status Report

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Published: 2021-07-13   Modified: 2024-01-30  

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