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2010 Fiscal Year Final Research Report

Optical Imaging of Intratumoral HIF-1 activity to Optimize Treatment Regimens for Chemoradiotherapy

Research Project

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Project/Area Number 21791184
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Radiation science
Research InstitutionKyoto University

Principal Investigator

HARADA Hiroshi  Kyoto University, 生命科学系キャリアパス形成ユニット, 講師 (80362531)

Project Period (FY) 2009 – 2010
Keywords放射線 / 腫瘍(がん) / 低酸素 / 微小環境 / 光イメージング
Research Abstract

Here, I and my colleagues performed a series of optical imaging experiments to visualize intratumoral HIF-1 activity, and optimized some combination of radiation with antitumor drugs, which could modulate HIF-1 activity, such as a VEGF neutralizing agent, bevacizumab, and a HIF-1 inhibitor, YC-1.
1. Optical imaging experiments showed that administration of a VEGF-neutralizing agent, bevacizumab, temporally induced vascular normalization and decreased hypoxic fraction in tumor xenografts 1 day after the treatment. When radiation treatment was given in this timing, the combined treatment significantly delayed tumor growth compared to radiation therapy alone.
2. We found that administration of a HIF-1 inhibitor, YC-1, suppressed radiation-induced activation of intratumoral HIF-1 activity, and then significantly delayed the growth of recurrent tumor after radiation therapy.

  • Research Products

    (44 results)

All 2011 2010 2009 Other

All Journal Article (18 results) Presentation (19 results) Book (6 results) Remarks (1 results)

  • [Journal Article] AHR, a novel acute hypoxia-response sequence, drives reporter gene under hypoxia in vitro and in vivo.2011

    • Author(s)
      Cilek MZ, Hirohata S, Hatipoglu OF, Ogawa H, Miyoshi T, Inagaki J, Ohtsuki T, Harada H, Kamikawa S, Kusachi S, Ninomiya Y.
    • Journal Title

      Cell Biol Int. 35

      Pages: 1-8

  • [Journal Article] Synthesis and biological evaluation of indolyl chalcones as antitumor agents.2010

    • Author(s)
      Kumar D, Kumar NM, Akamatsu K, Kusaka E, Harada H, Ito T.
    • Journal Title

      Bioorg Med Chem Lett. 20

      Pages: 3916-3919

  • [Journal Article] Indolequinone-rhodol conjugate as fluorescent probe for hypoxic cells : enzymatic activation and fluorescence properties.2010

    • Author(s)
      Komatsu H, Harada H, Tanabe K, Hiraoka M, Nishimoto S.
    • Journal Title

      MedChemComm. 1

      Pages: 50-53

  • [Journal Article] Hypoxia-inducible factor 1 in Tumor Radioresistance.2010

    • Author(s)
      Harada H, Hiraoka M.
    • Journal Title

      Current Signal Transduction Therapy. 5

      Pages: 188-196

  • [Journal Article] A novel strategy to tag matrix metalloproteinases-positive cells for in vivo imaging of invasive and metastatic activity of tumor cells.2010

    • Author(s)
      Zhao T, Harada H, Teramura Y, Tanaka S, Itasaka S, Moriniibu A, Shinomiya K, Zhu Y, Hanaoka H, Iwata H, Saji H, Hiraoka M.
    • Journal Title

      J Control Release. 144

      Pages: 109-114

  • [Journal Article] Ring-opening metathesis polymerization-based synthesis of polymeric nanoparticle for enhanced tumor imaging in vivo : Synergistic effect of folate-receptor targeting and PEGylation.2010

    • Author(s)
      Miki K, Oride K, Inoue S, Kuramochi Y, Nayak RR, Matsuoka H, Harada H, Hiraoka M, Ohe K.
    • Journal Title

      Biomaterials. 31

      Pages: 934-942

  • [Journal Article] Monitoring of Hypoxia-selective Enzymatic Reduction of Indolequinone derivative by 19F-NMR.2009

    • Author(s)
      Tanabe K, Komatsu H, Harada H, Hiraoka M, Nishimoto S.
    • Journal Title

      Photomedicine and Photobiology. 31

      Pages: 31-32

  • [Journal Article] The Akt/mTOR pathway assures the synthesis of HIF-1alpha protein in a glucose- and reoxygenation-dependent manner in irradiated tumors.2009

    • Author(s)
      Harada H, Itasaka S, Kizaka-Kondoh S, Shibuya K, Morinibu A, Shinomiya K, Hiraoka M.
    • Journal Title

      J.Biol.Chem. 284

      Pages: 5332-5342

  • [Journal Article] The intravenous anesthetics barbiturates inhibit hypoxia-inducible factor 1 activation.2009

    • Author(s)
      Wakamatsu T, Tanaka T, Oda S, Nishi K, Harada H, Daijo H, Takabuchi S, Fukuda K, Hirota K.
    • Journal Title

      Euro J Pharm. 617

      Pages: 17-22

  • [Journal Article] Treatment regimen determines whether a HIF-1 inhibitor enhances or inhibits the effect of radiation therapy.2009

    • Author(s)
      Harada H, Itasaka S, Zhu Y, Zeng L, Xie X, Morinibu A, Shinomiya K, Hiraoka M.
    • Journal Title

      Br J Cancer. 100

      Pages: 747-757

  • [Journal Article] The HIF-1-active microenvironment : An environmental target for cancer therapy.2009

    • Author(s)
      Kizaka-Kondoh S, Tanaka S, Harada H, Hiraoka M.
    • Journal Title

      Adv Drug Deliv Rev. 61

      Pages: 623-632

  • [Journal Article] HIF imaging is useful to determine the timing of combining Bevacizumab with radiation.2009

    • Author(s)
      Ou G, Itasaka S, Zeng L, Shibuya K, Yi J, Harada H, Hiraoka M.
    • Journal Title

      Int J Radiat Oncol Biol Phys. 75

      Pages: 463-467

  • [Journal Article] Monitoring of biological one-electron reduction by 19F-NMR using hypoxia selective activation of a 19F-labeled indolequinone derivative.2009

    • Author(s)
      Tanabe K, Harada H, Narazaki M, Tanaka K, Inafuku K, Komatsu H, Ito T, Yamada H, Chujo Y, Matsuda T, Hiraoka M, Nishimoto S.
    • Journal Title

      J Am Chem Soc. 131

      Pages: 15982-15983

  • [Journal Article] Ring-Opening Metathesis Polymerization-Based Synthesis of ICG-Containing Amphiphilic Triblock Copolymers for in Vivo Tumor Imaging.2009

    • Author(s)
      Miki K, Kuramochi Y, Oride K, Inoue S, Harada H, Hiraoka M, Ohe K.
    • Journal Title

      Bioconjugate Chem. 20

      Pages: 511-517

  • [Journal Article] Radiolytic activation of cytarabine prodrug possessing 2-oxoalkyl group: one-electron reduction and cytotoxicity characteristics.2009

    • Author(s)
      Hirata N, Fujisawa Y, Tanabe K, Harada H, Hiraoka M, Nishimoto S.
    • Journal Title

      Org Biomol Chem. 7

      Pages: 651-654

  • [Journal Article] Aigiogenic roles of adrenomodulin through VEGF induction.

    • Author(s)
      Maki T, Ihara M, Fujita Y, Nambu T, Harada H, Ito H, Nakao K, Tomimoto H, Takahashi R.
    • Journal Title

      NeuroReport. (in press)

  • [Journal Article] Effective encapsulation of a new cationic gadolinium chelate into apoferitin and its evaluation as a MRI contrast agent.

    • Author(s)
      Makino A, Harada H, Okada T, Kimura H, Amano H, Saji H, Hiraoka M, Kimura S.
    • Journal Title

      Nanomedicine. (in press)

  • [Journal Article] Angiogenic and vasoprotective effects of adrenomedulin on prevention of cognitive decline after chronic cerebral hypoperfusion in mice.

    • Author(s)
      Maki T, Ihara M, Fujita Y, Nambu T, Miyashita K, Yamada M, Washida K, Nishio K, Ito H, Harada H, Yokoi H, Arai H, Itoh H, Nakao K, Takahashi R, Tomimoto H.
    • Journal Title

      Stroke. (in press.)

  • [Presentation] 放射線生物学的視点で迫る「腫瘍低酸素・放射線抵抗性・がん再発の時空間関係」2011

    • Author(s)
      原田浩
    • Organizer
      第13回国際癌治療増感シンポジウム
    • Place of Presentation
      奈良
    • Year and Date
      20110211-20110212
  • [Presentation] Tracking the dynamics of hypoxic tumor cells during tumor growth and after radiation therapy.2011

    • Author(s)
      Harada H.
    • Organizer
      The 1st International Symposium for Molecular-targeting Radiation Therapy.
    • Place of Presentation
      Kyoto.
    • Year and Date
      20110203-20110204
  • [Presentation] 光イメージングで迫る放射線治療後のがん再発メカニズム2010

    • Author(s)
      原田浩
    • Organizer
      東北大学大学院医学研究科附属創生応用医学研究センター酸素医学コアセンターシンポジウム
    • Place of Presentation
      仙台
    • Year and Date
      2010-11-19
  • [Presentation] 高精度放射線治療法の確立を見据えた低酸素イメージングの方向性2010

    • Author(s)
      原田浩
    • Organizer
      第50回日本核医学会学術総会シンポジウム:放射線治療計画に貢献するPET/CTの展望
    • Place of Presentation
      大宮ソニックシティ
    • Year and Date
      2010-11-12
  • [Presentation] 放射線治療後のがん局所再発における低酸素がん細胞の動態2010

    • Author(s)
      原田浩
    • Organizer
      第53回日本放射線影響学会
    • Place of Presentation
      京都テルサ
    • Year and Date
      2010-10-21
  • [Presentation] 低酸素がん細胞の腫瘍内ダイナミクスと放射線治療抵抗性2010

    • Author(s)
      原田浩
    • Organizer
      第69回日本癌学会学術総会シンポジウム#17.
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-09-23
  • [Presentation] 低酸素がん細胞の腫瘍内動態解析~がんの再発メカニズムの解明~2010

    • Author(s)
      原田浩
    • Organizer
      群馬大学Clinical Oncology Research研究会
    • Place of Presentation
      群馬大学
    • Year and Date
      2010-06-03
  • [Presentation] Tracking the Dynamics of Hypoxic Tumor Cells during Local Tumor Recurrence after Radiation Therapy.2010

    • Author(s)
      Harada H.
    • Organizer
      Fourth Military Medical University Seminar. Xi'an, China.
    • Year and Date
      2010-05-24
  • [Presentation] Reoxygenation, HIF-1, and Radioresistance.2010

    • Author(s)
      原田浩
    • Organizer
      第12回癌治療増感研究シンポジウム
    • Year and Date
      2010-02-14
  • [Presentation] HIF-1の活性化を介した癌の巧妙な放射線耐性機構~in vivo光イメージングによるアプローチ~2009

    • Author(s)
      原田浩
    • Organizer
      第41回日本臨床分子形態学会
    • Place of Presentation
      神戸
    • Year and Date
      20090903-20090905
  • [Presentation] 低酸素誘導性因子-1(HIF-1)による癌の放射線耐性機構の解明とその克服2009

    • Author(s)
      原田浩
    • Organizer
      第52回日本放射線影響学会
    • Place of Presentation
      広島
    • Year and Date
      2009-11-13
  • [Presentation] Peri-necrotic tumor cells cause recurrence after radiotherapy through migration to tumor blood vessels.2009

    • Author(s)
      Harada H.
    • Organizer
      International Symposium/Retreat, Kyoto University Global COE Program
    • Place of Presentation
      Center for Frontier Medicine.
    • Year and Date
      2009-11-07
  • [Presentation] Optical Imaging of Tumo Hypoxia, Cell Cycle, pH, and DNA double strand breaks to Analyze the Molecular Mechanism Underlying Tumor Radioresistance.2009

    • Author(s)
      Harada H.
    • Organizer
      3rd International Symposium on Nanomedicine.
    • Year and Date
      2009-11-04
  • [Presentation] A Molecular Mechanism Underlying HIF-1-mediated Tumor Radioresistance.2009

    • Author(s)
      原田浩
    • Organizer
      2009年度日本癌学会
    • Year and Date
      2009-10-03
  • [Presentation] Optical Imaging of Intratumoral HIF-1 Activity to Elucidate the Mechanism Underlying HIF-1-mediated Tumor Radioresistance.2009

    • Author(s)
      Harada H.
    • Organizer
      Two Interests Seminars at Gray Institute for Radiation Oncology & Biology, University of Oxford.
    • Place of Presentation
      Oxford. United Kingdom.
    • Year and Date
      2009-09-25
  • [Presentation] がんの放射線耐性機構の解明と放射線治療への展開-HIF-1活性のイメージング研究に基づく提言-2009

    • Author(s)
      原田浩
    • Organizer
      第39回放射線による制癌シンポジウム
    • Place of Presentation
      富山
    • Year and Date
      2009-07-11
  • [Presentation] Tumor Hypoxia : A Microenvironmental Target in Cancer Therapy.2009

    • Author(s)
      Harada H.
    • Organizer
      Asian Association of Radiation Research (AARR) Award Session in 2nd Asian Congress for Radiation Research (ACRR).
    • Place of Presentation
      Seoul, Korea.
    • Year and Date
      2009-05-20
  • [Presentation] Optical Imaging of Intratumoral HIF-1 Activity to Elucidate the Mechanism Underlying HIF-1-mediated Tumor Radioresistance.2009

    • Author(s)
      Harada H.
    • Organizer
      Symposium #10 (Tumor Microenvironment) in 2nd Asian Congress for Radiation Research (ACRR).
    • Place of Presentation
      Seoul, Korea.
    • Year and Date
      2009-05-19
  • [Presentation] Identification of the source of Tumor recurrence after radiation therapy.2009

    • Author(s)
      Harada H.
    • Organizer
      Radiation Oncology Seminar in Seoul National University, Seoul.
    • Year and Date
      2009-05-18
  • [Book] Pharmaceutical Perspectives of Cancer Therapeutics.Springer(Protein Transduction Domain-mediated Delivery of Anti-cancer Drugs and Proteins.Lu Y and Mahato RI)(eds).2009

    • Author(s)
      Harada H, Hiraoka M.
    • Total Pages
      297-319
  • [Book] 癌の臨床(がんの放射線抵抗性機構の解明と放射線治療への展開-HIF-1活性のイメージング研究に基づく提言),552009

    • Author(s)
      原田浩、平岡真寛
    • Total Pages
      847-853
  • [Book] 放射線生物研究(2nd Asian Congress of Radiation Research(アジア放射線研究会議)に参加して-世界の放射線科学研究の動向分析-),442009

    • Author(s)
      原田浩
    • Total Pages
      360-363
  • [Book] 放射線生物研究(Hypoxia-inducible Factor-1(HIF-1)による放射線治療後の腫瘍増殖亢進機構),442009

    • Author(s)
      原田浩平岡真寛
    • Total Pages
      60-69
  • [Book] Targets in Gene Therapy.(Gene Therapy Strategy for Tumor Hypoxia.)

    • Author(s)
      Harada H.
    • Publisher
      (in press.)
  • [Book] からだと酸素の辞典(低酸素がん細胞の光学イメージング)

    • Author(s)
      原田浩、平岡真寛
    • Publisher
      (印刷中)
  • [Remarks] ホームページ等

    • URL

      http://www.cp.kyoto-u.ac.jp/Harada/

URL: 

Published: 2012-02-13   Modified: 2016-04-21  

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