• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of molecular imaging tracers for anticancer drug resistant proteins

Research Project

Project/Area Number 21390409
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionNagoya University

Principal Investigator

WAKABAYASHI Toshihiko  名古屋大学, 大学院・医学系研究科, 教授 (50220835)

Co-Investigator(Kenkyū-buntansha) NATSUME Atsushi  名古屋大学, 大学院・医学系研究科, 准教授 (30362255)
SUZUKI Masaaki  独立行政法人理化学研究所, 分子イメージング科学研究センター, 副センター長 (90093046)
KOYAMA Hiroko  岐阜大学, 大学院・医学系研究科, 助教 (50402160)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2010: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2009: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Keywords分子イメージング / 脳腫瘍 / 分子イメーグング / MGMT / PETトレーサー / 分子 / イメージング / 有機合成 / 臨床応用
Research Abstract

The DNA repair protein O6-methylguanine-DNA methyltransferase(MGMT, AGT) is a determinant of the resistance of tumor cells to alkylating anticancer agents that target the O6 position of guanine. MGMT promoter methylation in tumors is regarded as the most common predictor of the responsiveness of glioblastoma to alkylating agents. However, MGMT promoter methylation status has been investigated mainly by methylation-specific PCR(MSP), which is a qualitative and subjective assay. In addition, the actual enzymatic activities associated with the methylation status of MGMT have not been explored. In the present study, we aimed to create a novel non-invasive MGMT imaging rather than MSP. First, we performed bisulfite pyrosequencing, and its correlation with enzymatic activity was determined using a novel quantitative assay for studying the functional activity of MGMT. MGMT enzymatic activity was assessed using fluorometrically labeled oligonucleotide substrates containing MGMT-specific DNA lesions and capillary electrophoresis to detect and quantify these lesions. In comparison with existing traditional assays, this assay was equally sensitive but less time consuming and easier to perform. MGMT promoter methylation was assessed in 41 glioblastomas by bisulfite pyrosequencing, and 5 samples with different values were chosen for comparison with enzymatic assays. In comparative studies, MGMT promoter methylation values obtained by bisulfite pyrosequencing were inversely proportional to the measured enzymatic activity. The present results indicate that the quantification of MGMT methylation by bisulfite pyrosequencing represents its enzymatic activity and thus, its therapeutic responsiveness to alkylating agents.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (62 results)

All 2011 2010 2009

All Journal Article (22 results) (of which Peer Reviewed: 9 results) Presentation (31 results) Book (9 results)

  • [Journal Article] A multicenter phase I trial of combination therapy with interferon-beta and temozolomide for high-grade gliomas(INTEGRA study) the final report2011

    • Author(s)
      Wakabayashi T, Kayama T, Nishikawa R, Takahashi H, Hoshimoto N, TakahashiJ, Aoki T, Sugiyama K, Ogura M, Natsume A, Yoshida J.
    • Journal Title

      J Neurooncol

      Volume: 14

    • Related Report
      2011 Final Research Report
  • [Journal Article] Benefits of interferon-beta and temozolomide combination therapy for newly diagnosed primary glioblastoma with the unmethylated MGMT promoter2011

    • Author(s)
      Motomura K, Natsume A, Kishida Y, Higashi H, Kondo Y, Nakasu Y, Abe T, Namba H, Wakai K, Wakabayashi T.
    • Journal Title

      A multicenter study

      Volume: 117 Pages: 1721-1730

    • Related Report
      2011 Final Research Report
  • [Journal Article] Cytokine networks in glioma2011

    • Author(s)
      Iwami K, Natsume A, Wakabayashi T
    • Journal Title

      Neurosurg Rev

      Volume: 第34巻 Pages: 253-264

    • Related Report
      2011 Final Research Report
  • [Journal Article] Long-term survival in patients with newly diagnosed primary central nervous system lymphoma treated with dexamethasone, etoposide2011

    • Author(s)
      Motomura K, Natsume A, Fujii M, Ito M, Momota H, Wakabayashi T
    • Journal Title

      Leukemia and Lymphoma Epub ahead of print

    • Related Report
      2011 Final Research Report
  • [Journal Article] The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promotor methylation and is a better prognostic factor for glioma2011

    • Author(s)
      Ohka F, Natsume A, Motomura K, KishidaY, Kondo Y, Abe T, Nakasu Y, Namba H, Wakai K, Fukui T, Momota H, Iwami K, Kinjo S, Ito M, Fujii M, Wakabayashi T
    • Journal Title

      PLoS One

      Volume: 6(8)

    • Related Report
      2011 Final Research Report
  • [Journal Article] Intravenous administration of temozolomide as a useful alternative over oral treatment with temozolomide capsules in patients with gliomas2011

    • Author(s)
      Motomura K, Natsume A, Wakabayashi T
    • Journal Title

      J Neurooncol

      Volume: 13

    • Related Report
      2011 Final Research Report
  • [Journal Article] Glioma-initiating cells and molecular pathology2011

    • Author(s)
      Natsume A, Kinjo S, Yuki K, Kato T, Ohno M, Motomura K, Iwami K, Wakabayashi T
    • Journal Title

      Implications for therapy Brain

      Volume: 28 Pages: 1-28

    • Related Report
      2011 Final Research Report
  • [Journal Article] Rhabdoid glioblastoma in a child2011

    • Author(s)
      Momota H, Iwami K, Fujii M, MotomuraK, Natsume A, Ogino J, Hasegawa T, Wakabayashi T
    • Journal Title

      case report and literature review

      Volume: 28 Pages: 65-70

    • Related Report
      2011 Final Research Report
  • [Journal Article] The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promotor methylation and is a better prognostic factor for glioma2011

    • Author(s)
      Ohka F, Natsume A, Wakabayashi T
    • Journal Title

      PLoS One

      Volume: 6

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term survival in patients with newly diagnosed primary central nervous system lymphoma treated with dexamethasone, etoposide, ifosfamide and carboplatin chemotherapy and whole-brain radiation therapy2011

    • Author(s)
      Motomura K, Natsume A, Wakabayashi T
    • Journal Title

      Leukemia and Lymphoma

      Volume: (印刷中)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytokine networks in glioma2011

    • Author(s)
      Iwami K, Wakabayashi T
    • Journal Title

      Neurosurg Rev

      Volume: 34 Pages: 253-264

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human neural stem cells transduced with IFN-beta and cytosine deaminase genes intensify bystander effect in experimental glioma2010

    • Author(s)
      S Ito, A Natsume, S Shimato, M Ohno, T Kato, P Chansakul, T Wakabayashi, SUKim.
    • Journal Title

      Cancer Gene Ther

      Volume: 17 Pages: 299-306

    • Related Report
      2011 Final Research Report
  • [Journal Article] Epigenetic aberrations and therapeutic implications in gliomas2010

    • Author(s)
      A Natsume, Y Kondo, M Ito, K Momota, T Wakabayashi, J Yohida
    • Journal Title

      Cancer Scinece

      Volume: 101(6) Pages: 1331-1336

    • NAID

      10026592977

    • Related Report
      2011 Final Research Report
  • [Journal Article] Efficient delivery of liposome-mediated MGMT-siRNA reinforces the cytotoxity of temozolomide in GBM-initiating cells2010

    • Author(s)
      T Kato, A Natsume, H Toda, H Iwazumi, T Sugita, R Hachisu, R Watanabe, KYuki, K Motomura, K Bankiewicz, T Wakabayashi
    • Journal Title

      Gene Therapy

      Volume: 17(11) Pages: 1363-1371

    • Related Report
      2011 Final Research Report
  • [Journal Article] Retrovirally engineered T cell-based immunotherapy targeting type-III variant epidermal growth factor receptor, a gloma-associated antigen2010

    • Author(s)
      M Ohno, A Natsume, H Iwamizu, D Ito, Y Toi, K Iwami, K Noritake, M Ito, KMotomura, J Yoshida, K Yoshikawa, T Wakabayashi
    • Journal Title

      Cancer Scinece

      Volume: 101(12) Pages: 2518-2524

    • Related Report
      2011 Final Research Report
  • [Journal Article] A free-radical scavenger protects the neural progenitor cells in the dentate subgranular zone of the hippocampus from cell death after X-irradiation2010

    • Author(s)
      Motomura K, Ogura M, Natsume A, Yokoyama H, Wakabayashi T
    • Journal Title

      Neuroscience Letters

      Volume: 485(1) Pages: 65-70

    • Related Report
      2011 Final Research Report
  • [Journal Article] Retrovirally engineered T-cell-based immunotherapy targeting type-III variant epidermal growth factor receptor, a glioma-associated antigen2010

    • Author(s)
      Ohno M, Natsume A, et al
    • Journal Title

      Cancer Science

      Volume: 101 Pages: 2518-24

    • NAID

      10027834208

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient delivery of liposome-mediated MGMT-siRNA reinforces the cytotoxity of temozolomide in GBM-initiating cells2010

    • Author(s)
      Kato T, Natsume A, et al
    • Journal Title

      Gene Therapy

      Volume: 17 Pages: 1363-71

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic aberrations and therapeutic implications in gliomas2010

    • Author(s)
      Natsume A, et al
    • Journal Title

      Cancer Science

      Volume: 101 Pages: 1331-6

    • NAID

      10026592977

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Type I interferon inhibits astrocytic gliosis and promote functional r2009

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

      Journal of Neurotrauma

      Volume: 26 Pages: 41-53

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human neural stem cells transduced with IFN-beta and cytosine2009

    • Author(s)
      Ito S, et al.
    • Journal Title

      Cancer Gene Therapy

      Volume: 1 Pages: 1-2

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The modulation of microRNAs by type I IFN through the activation2009

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

      Molecular Cancer Research

      Volume: 7 Pages: 2022-2030

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 膠芽腫の治療経験から次の戦略を探る2011

    • Author(s)
      若林俊彦
    • Organizer
      第5回信州脳腫瘍研究会
    • Place of Presentation
      松本
    • Year and Date
      2011-10-28
    • Related Report
      2011 Final Research Report
  • [Presentation] 悪性脳腫瘍の治療戦略2011

    • Author(s)
      若林俊彦
    • Organizer
      ノーベルファーマ全体研修会
    • Place of Presentation
      東京
    • Year and Date
      2011-02-18
    • Related Report
      2011 Final Research Report
  • [Presentation] 脳腫瘍治療の近未来を担うシーズを探る2011

    • Author(s)
      若林俊彦
    • Organizer
      第25回熊本脳神経外科懇話会
    • Place of Presentation
      熊本
    • Year and Date
      2011-02-18
    • Related Report
      2011 Final Research Report
  • [Presentation] 脳神経疾患に対する脳外科医療の現状と今後の展望2011

    • Author(s)
      若林俊彦
    • Organizer
      大同病院学術講演会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-02-12
    • Related Report
      2011 Final Research Report
  • [Presentation] Clinical trial of Interferon-beta and Temozolomide combination therapy for malignant glioma with radiotherapy2011

    • Author(s)
      若林俊彦
    • Organizer
      財団法人がん研究振興財団第24回国際がん研究シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] Sugita scholarship program2011

    • Author(s)
      若林俊彦
    • Organizer
      The 79th AANS
    • Place of Presentation
      Denver
    • Related Report
      2011 Final Research Report
  • [Presentation] 悪性脳腫瘍治療の最近の知見2011

    • Author(s)
      若林俊彦
    • Organizer
      第31回日本脳神経外科コングレス総会
    • Place of Presentation
      横浜(招待講演)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 最近の悪性脳腫瘍治療の進歩2011

    • Author(s)
      若林俊彦
    • Organizer
      第52回日本神経学会学術集会
    • Place of Presentation
      東京(招待講演)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 悪性脳腫瘍治療のブレイクスルーを目指して2010

    • Author(s)
      若林俊彦
    • Organizer
      南大阪最先端医療研究会
    • Place of Presentation
      大阪
    • Year and Date
      2010-10-22
    • Related Report
      2011 Final Research Report
  • [Presentation] 悪性脳腫瘍に対する分子標的療法を目指した遺伝子治療の今後の展望2010

    • Author(s)
      若林俊彦
    • Organizer
      第52回千葉神経外科研究会
    • Place of Presentation
      千葉
    • Year and Date
      2010-10-15
    • Related Report
      2011 Final Research Report
  • [Presentation] 悪性神経膠腫の治療成績向上を目指した治療戦略2010

    • Author(s)
      若林俊彦
    • Organizer
      第5回青森県脳腫瘍セミナー
    • Place of Presentation
      弘前
    • Year and Date
      2010-09-17
    • Related Report
      2011 Final Research Report
  • [Presentation] 悪性腫瘍克服の実現に向けて2010

    • Author(s)
      若林俊彦
    • Organizer
      第3回玄海脳腫瘍セミナー
    • Place of Presentation
      博多
    • Year and Date
      2010-07-09
    • Related Report
      2011 Final Research Report
  • [Presentation] 悪性神経膠腫の術後補助療法の治療戦略2010

    • Author(s)
      若林俊彦
    • Organizer
      第1回京都脳腫瘍セミナー
    • Place of Presentation
      大阪
    • Year and Date
      2010-07-03
    • Related Report
      2011 Final Research Report
  • [Presentation] 悪性脳腫瘍治療戦略の基礎的研究から臨床最前線まで2010

    • Author(s)
      若林俊彦
    • Organizer
      第113回山口県脳神経外科懇話会
    • Place of Presentation
      宇部
    • Year and Date
      2010-06-26
    • Related Report
      2011 Final Research Report
  • [Presentation] 悪性脳腫瘍への挑戦:INTEGRA studyに期待すること2010

    • Author(s)
      若林俊彦
    • Organizer
      第10回高知県脳神経外科研究会
    • Place of Presentation
      高知
    • Year and Date
      2010-06-25
    • Related Report
      2011 Final Research Report
  • [Presentation] 遺伝性脳腫瘍の病理と臨床2010

    • Author(s)
      若林俊彦
    • Organizer
      第28回日本脳腫瘍病理学会
    • Place of Presentation
      大阪
    • Year and Date
      2010-05-22
    • Related Report
      2011 Final Research Report
  • [Presentation] 脳神経外科領域におけるNano-surgeryへの展開2010

    • Author(s)
      若林俊彦
    • Organizer
      ナノ学会第8回大会
    • Place of Presentation
      名古屋
    • Year and Date
      2010-05-13
    • Related Report
      2011 Final Research Report
  • [Presentation] テモダールをはじめとした化学療法の最新の治療成績と今後の展望2010

    • Author(s)
      若林俊彦、夏目敦至、藤井正純、渋井壮一郎
    • Organizer
      第30回日本脳神経外科コングレス総会
    • Place of Presentation
      横浜
    • Year and Date
      2010-05-07
    • Related Report
      2011 Final Research Report
  • [Presentation] ニューロサイエンスに基づく脳神経外科医療の進歩2010

    • Author(s)
      若林俊彦
    • Organizer
      奈良県立医科大学脳神経外科教室開講50周年記念講演会
    • Place of Presentation
      大阪
    • Year and Date
      2010-04-24
    • Related Report
      2011 Final Research Report
  • [Presentation] 膠芽腫の生命予後改善に向けた集学的治療の工夫2010

    • Author(s)
      若林俊彦
    • Organizer
      脳腫瘍治療のUp to date
    • Place of Presentation
      愛媛
    • Year and Date
      2010-04-23
    • Related Report
      2011 Final Research Report
  • [Presentation] Gene therapy for malignant glioma ; Current status and future prospect2010

    • Author(s)
      若林俊彦
    • Organizer
      The 28th annual spring meeting of the Korean Neurosurgical Society
    • Place of Presentation
      Busan(釜山)
    • Year and Date
      2010-04-09
    • Related Report
      2011 Final Research Report
  • [Presentation] INTEGRA study :開発の経緯と今後の展望2010

    • Author(s)
      若林俊彦
    • Organizer
      徳島脳腫瘍セミナー2010
    • Place of Presentation
      徳島
    • Year and Date
      2010-02-22
    • Related Report
      2011 Final Research Report
  • [Presentation] 脳神経外科手術戦略と術後補助療法の今後の展開2010

    • Author(s)
      若林俊彦
    • Organizer
      第1回沖縄県テモダール講演会
    • Place of Presentation
      那覇
    • Year and Date
      2010-02-05
    • Related Report
      2011 Final Research Report
  • [Presentation] 膠芽腫の世界的標準治療の日本からの発信を目指して2010

    • Author(s)
      若林俊彦
    • Organizer
      第3回金沢脳腫瘍セミナー
    • Place of Presentation
      金沢
    • Year and Date
      2010-01-30
    • Related Report
      2011 Final Research Report
  • [Presentation] 悪性脳腫瘍に対する先駆的治療戦略2010

    • Author(s)
      若林俊彦
    • Organizer
      第60回山形脳神経外科懇話会
    • Place of Presentation
      山形
    • Year and Date
      2010-01-15
    • Related Report
      2011 Final Research Report
  • [Presentation] 初発膠芽腫に対するIFN-b+テモダール併用化学放射線療法のランダム化第2相試験2010

    • Author(s)
      若林俊彦、夏目敦至、藤井正純、渋井壮一郎
    • Organizer
      第69回日本脳神経外科学会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2011 Final Research Report
  • [Presentation] Mulitomodal treatment strategy for glioma2010

    • Author(s)
      若林俊彦
    • Organizer
      the 4th Indian Japanese Friendship Neurosurgicla Meeting
    • Place of Presentation
      Cochin
    • Related Report
      2011 Final Research Report
  • [Presentation] Recent Advanced neurosurgical procedure using integrated system of intraoperative MRI and neuronavigation with multimodal neuroradiological images2010

    • Author(s)
      若林俊彦
    • Organizer
      The 4th harpin international neurosurgical meeting in china 2010
    • Place of Presentation
      ハルピン
    • Related Report
      2011 Final Research Report
  • [Presentation] Mulitomodal treatment strategy for glioma2010

    • Author(s)
      若林俊彦
    • Organizer
      the 4th Indian Japanese Friendship Neurosurgicla Meeting
    • Place of Presentation
      Cochin, India
    • Related Report
      2010 Annual Research Report
  • [Presentation] 脳腫瘍診療の現状とPETへの期待2009

    • Author(s)
      若林俊彦
    • Organizer
      日本メジフィジックス社内講演会
    • Place of Presentation
      東京
    • Year and Date
      2009-12-25
    • Related Report
      2011 Final Research Report
  • [Presentation] A Japanese multicenter clinical trial of interferon-beta and temozolomide2009

    • Author(s)
      Wakabayashi T
    • Organizer
      The 17^<th> International conference of brain tumor research and therapy
    • Place of Presentation
      Hakodate, Japan
    • Year and Date
      2009-06-09
    • Related Report
      2009 Annual Research Report
  • [Book] 脳神経外科速報2011

    • Author(s)
      若林俊彦
    • Publisher
      メディカ出版
    • Related Report
      2011 Final Research Report
  • [Book] 化学とマイクロ・ナノシステム研究脳神経外科領域におけるマイクロナノシステムの臨床への応用2011

    • Author(s)
      若林俊彦、夏目敦至、藤井正純、吉田純
    • Related Report
      2011 Final Research Report
  • [Book] 免疫細胞治療II難治性の悪性グリオーマに対する治療戦略のブレイクスルー(突破口)を免疫治療に期待したい2011

    • Author(s)
      田中怜子
    • Publisher
      幻冬舎
    • Related Report
      2011 Final Research Report
  • [Book] 脳腫瘍の外科ー社会が望む脳腫瘍外科/術中MRI時代のlowgrade glioma手術戦略2011

    • Author(s)
      大畑健治
    • Publisher
      ミック大阪
    • Related Report
      2011 Final Research Report
  • [Book] 先達の息吹2011

    • Author(s)
      宮本享
    • Publisher
      メディカ出版
    • Related Report
      2011 Final Research Report
  • [Book] 新しい手術のモダリティー2011

    • Author(s)
      桑野博
    • Publisher
      総合医学社
    • Related Report
      2011 Final Research Report
  • [Book] 神経膠腫ー診断から治療までー画像診断と外科治療の融合2011

    • Author(s)
      若林敏彦、夏目敦至、藤井正純
    • Publisher
      秀潤社
    • Related Report
      2011 Final Research Report
  • [Book] 新時代の脳腫瘍学:診断・治療の最前線IV.脳腫瘍の診断脳腫瘍の腫瘍マーカー神経膠腫2011

    • Author(s)
      若林俊彦
    • Publisher
      日本臨床
    • Related Report
      2011 Annual Research Report
  • [Book] 脳腫瘍臨床病理カラーアトラス(第3版)Astrocytoma grade IV ; Glioblastoma2010

    • Author(s)
      若林俊彦
    • Total Pages
      250
    • Publisher
      医学書院
    • Related Report
      2010 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi