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Epigenetic Analyses of Brain Tumors for Development of Diagnosis and Treatment in the Era of Postgenome

Research Project

Project/Area Number 19591669
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NATSUME Atsushi  Nagoya University, 医学部附属病院, 特任准教授 (30362255)

Co-Investigator(Kenkyū-buntansha) YOSHIDA Jun  名古屋大学, 大学院・医学系研究科, 教授 (40158449)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords脳腫瘍 / 遺伝子 / ゲノム / エピジェネティクス / 診断 / 治療 / DNAメチル化 / MGMT / パイロシークエンス / マイクロアレイ / 脳腫瘍幹細胞 / 免疫療法 / 組織培養 / 脳腫瘍の起源
Research Abstract

本研究では、pyrosequenceを用いてエピジェネティクなDNAメチル化変化を定量することを試みた。Pyrosequence法は、従来のmethylation-specific PCR(MSP)の不定量性を改良した斬新な方法である。MSPでは、メチル化の有無しか判定できないのに対し、Pyrosequencingではグリオーマの腫瘍組織は0-90%にわたる広範囲なメチル化が起こることを認めた。基準値を設けるとMSPとの相関も認められた。また、免疫組織染色との相関、テモゾロミドを投与した神経膠腫症例における予後との相関についても検討した。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (53 results)

All 2009 2008 2007 Other

All Journal Article (30 results) (of which Peer Reviewed: 12 results) Presentation (19 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Interferon-beta, MCNU, and conventional radiotherapy for pediatric patients with brainstem glioma2009

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

      Pediatr Blood Cancer (in press)

    • Related Report
      2008 Final Research Report
  • [Journal Article] p16 promoter methylation in the serum as a basis for the molecular diagnosis of gliomas2009

    • Author(s)
      Wakabayashi T, Natsume A, Hatano H
    • Journal Title

      Neurosurgery 64(3)

    • Related Report
      2008 Final Research Report
  • [Journal Article] Synergistic induction of NY-ESO-1 antigen expression by a novel histone deacetylase inhibitor, valproic acid, with 5-aza-2'-deoxycytidine in glioma cells2009

    • Author(s)
      Oi S, Natsume A, Ito M
    • Journal Title

      J Neurooncol 92(1)

      Pages: 15-22

    • Related Report
      2008 Final Research Report
  • [Journal Article] Type I Interferon Inhibits Astrocytic Gliosis and Promotes Functional Recovery after Spinal Cord Injury by Deactivation of the MEK/ERK Pathway2009

    • Author(s)
      Ito M, Natsume A, Takeuchi H
    • Journal Title

      J Neurotrauma 26(1)

      Pages: 41-53

    • Related Report
      2008 Final Research Report
  • [Journal Article] Type I Interferon Inhibits Astrocytic Gliosis and Promotes Functional Recovery after Spinal Cord Injury by Deactivation of the MEK/ERK Path way.2009

    • Author(s)
      Ito M, Natsume A, Takeuchi H, et al.
    • Journal Title

      J Neurotrauma 26

      Pages: 41-53

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interferon-beta, MCNU, and conventional radiotherapy for pediatric patients with brainstem glioma.2009

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

      Pediatr Blood Cancer (In press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic induction of NY-ESO-1 antigen expression by a novel histone deacetylase inhibitor, valproic acid, with 5-aza-2'-deoxycytidine in glioma cells.2009

    • Author(s)
      Oi S, Natsume A, Ito M, et al.
    • Journal Title

      J Neurooncol 92

      Pages: 15-22

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p16 promoter methylation in the serum as a basis for the molecular diagnosis of gliomas.2009

    • Author(s)
      Wakabayashi T, Natsume A., Hatano H, et al.
    • Journal Title

      Neurosurgery 64

      Pages: 461-452

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A phase I clinical trial of interferon-beta gene therapy for high- grade glioma : novel findings from gene expression profiling and autopsy2008

    • Author(s)
      Wakabayashi T, Natsume A, Hashizume Y
    • Journal Title

      J Gene Med 10(4)

      Pages: 329-339

    • Related Report
      2008 Final Research Report
  • [Journal Article] A multicenter phase I trial of interferon-beta and temozolomide combination therapy for high-grade gliomas (INTEGRA Study)2008

    • Author(s)
      Wakabayashi T, Kayama T, Nishikawa R
    • Journal Title

      Jpn J Clin Oncol 38(10)

      Pages: 715-718

    • Related Report
      2008 Final Research Report
  • [Journal Article] Identification of a human leukocyte antigen-A24-restricted T-cell epitope derived from interleukin-13 receptor alpha2 chain, a glioma-associated antigen2008

    • Author(s)
      Shimato S, Natsume A, Wakabayashi T
    • Journal Title

      J Neurosurg 109(1)

      Pages: 117-122

    • Related Report
      2008 Final Research Report
  • [Journal Article] Gene therapy for high-grade glioma : current approaches and future directions2008

    • Author(s)
      Natsume A, Yoshida J
    • Journal Title

      Cell Adh Migr 2(3)

      Pages: 186-191

    • Related Report
      2008 Final Research Report
  • [Journal Article] The DNA demethylating agent 5-aza-2'-deoxycytidine activates NY-ESO-1 antigenicity in orthotopic human glioma2008

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

      Int J Cancer 122(11)

      Pages: 2542-2553

    • Related Report
      2008 Final Research Report
  • [Journal Article] A combination of IFN-beta and temozolomide in human glioma xenograft models : implication of p53-mediated MGMT downregulation2008

    • Author(s)
      Natsume A, Wakabayashi T, Ishii D
    • Journal Title

      Cancer Chemother Pharmacol 61(4)

      Pages: 653-659

    • Related Report
      2008 Final Research Report
  • [Journal Article] Variable DNA methylation patterns associated with progression of disease in hepatocellular carcinomas2008

    • Author(s)
      Gao W, Kondo Y, Shen L
    • Journal Title

      Carcinogenesis 29(10)

      Pages: 1901-1910

    • Related Report
      2008 Final Research Report
  • [Journal Article] A combination of IFN-beta and temozolomide in human glioma xenograft models : implication of p53-inediated MGMT downregulation.2008

    • Author(s)
      Natsume A, Wakabayashi T, Ishii D, et al.
    • Journal Title

      Cancer Chemother Pharmacol 61

      Pages: 653-659

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The DNA demethylating agent 5-aza-2'-deoxycytidine activates NY-ESO-1 antigenicity in orthotopic human glioma.2008

    • Author(s)
      Natsume A, Wakabayashi T, Tsujimura K, et al.
    • Journal Title

      Int J Cancer 122

      Pages: 2542-2553

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene therapy for high-grade glioma : current approaches and future directions.2008

    • Author(s)
      Natsume A, Yoshida J
    • Journal Title

      Cell Adh Migr 2

      Pages: 186-191

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a human leukocyte antigen-A24-restricted T-cell epitope derived from interleukin-13 receptor alpha2 chain, a glioma-associated antigen.2008

    • Author(s)
      Shimato S, Natsume A, Wakabayashi T, et al.
    • Journal Title

      J Neurosurg 109

      Pages: 117-122

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A phase I clinical trial of interferon-beta gene therapy for high-grade glioma : novel findings from gene expression profiling and autopsy.2008

    • Author(s)
      Wakabayashi T, Natsume A, Hashizume Y, et al.
    • Journal Title

      J Gene Med 10

      Pages: 329-339

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Aurora-B function increases formation of multinucleated cells in p53 gene deficient cells and enhances anti-tumor effect of temozolomide in human glioma cells2007

    • Author(s)
      Tsuno T, Natsume A, Katsumata S
    • Journal Title

      J Neurooncol 83(3)

      Pages: 249-258

    • Related Report
      2008 Final Research Report
  • [Journal Article] Intravenously transplanted human neural stem cells migrate to the injured spinal cord in adult mice in an SDF-1- and HGF-dependent manner2007

    • Author(s)
      Takeuchi H, Natsume A, Wakabayashi T
    • Journal Title

      Neurosci Lett 426(2)

      Pages: 69-74

    • Related Report
      2008 Final Research Report
  • [Journal Article] Human neural stem cells target and deliver therapeutic gene to experimental leptomeningeal medulloblastoma2007

    • Author(s)
      Shimato S, Natsume A, Takeuchi H
    • Journal Title

      Gene Ther 14(15)

      Pages: 1132-1142

    • Related Report
      2008 Final Research Report
  • [Journal Article] Malignant transformation-related genes in meningiomas : allelic loss on 1p36 and methylation status of p73 and RASSF1A2007

    • Author(s)
      Nakane Y, Natsume A, Wakabayashi T
    • Journal Title

      J Neurosurg 107(2)

      Pages: 398-404

    • Related Report
      2008 Final Research Report
  • [Journal Article] Genetically heterogeneous glioblastoma recurring with disappearance of 1p/19q losses : case report2007

    • Author(s)
      Ito M, Wakabayashi T, Natsume A
    • Journal Title

      Neurosurgery 61(1)

    • Related Report
      2008 Final Research Report
  • [Journal Article] The free-radical scavenger edaravone restores the differentiation of human neural precursor cells after radiation-induced oxidative stress2007

    • Author(s)
      Ishii J, Natsume A, Wakabayashi T
    • Journal Title

      Neurosci Lett 423(3)

      Pages: 225-230

    • Related Report
      2008 Final Research Report
  • [Journal Article] Efficacy of temozolomide is correlated with 1p loss and methylation of the deoxyribonucleic acid repair gene MGMT in malignant gliomas2007

    • Author(s)
      Ishii D, Natsume A, Wakabayashi T
    • Journal Title

      Neurol Med Chir (Tokyo) 47(8)

      Pages: 341-349

    • NAID

      110006368605

    • Related Report
      2008 Final Research Report
  • [Journal Article] Efficacy of temozolomide is correlated with 1p Loss and Methylation of the Deoxyribonucleic Acid Repair Gene MGMT in Malignant Gliomas2007

    • Author(s)
      Ishii D, Natsume A, Wakabayashi T, Hatano H, Asano Y, Takeuchi H, Shimato S, Ito M, Fujii M, Yoshida J.
    • Journal Title

      Neurol Med Chir (Tokyo) 47

      Pages: 341-350

    • NAID

      110006368605

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetically heterogenous glioblastoma recurring with disappearance of 1p/19q losses: case report2007

    • Author(s)
      Ito M, Wakabayashi T, Natsume A, Hatano H, Fujii M, Yoshida J.
    • Journal Title

      Neurosurgery 61

      Pages: 168-169

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Malignant transformation-related genes in meningioma: allelic loss on 1 p36 and methylation status of p73 and RASSF1A2007

    • Author(s)
      Nakane Y, Natsume A, Wakabayashi T, Oi S, Ito M, Inao S, Saito K, Yoshida J.
    • Journal Title

      J Neurosurg 107

      Pages: 398-404

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 脳腫瘍幹細胞の起源 : エピジェネティクス解析とポリコーム蛋白標的治療の開発2008

    • Author(s)
      夏目敦至
    • Organizer
      第26回日本脳腫瘍学会
    • Place of Presentation
      愛媛県
    • Related Report
      2008 Final Research Report
  • [Presentation] 脳腫瘍治療の最近の進歩2008

    • Author(s)
      夏目敦至
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Final Research Report
  • [Presentation] グリオーマ幹細胞に対する分子標的治療の開発2008

    • Author(s)
      夏目敦至
    • Organizer
      第67回日本脳神経外科学会総会
    • Place of Presentation
      盛岡
    • Related Report
      2008 Final Research Report
  • [Presentation] Characteristics of AtypicalMeningiomas2008

    • Author(s)
      Natsume,A
    • Organizer
      6th International Congress on Meningiomas and Cerebral Venous System
    • Place of Presentation
      Boston, MA, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] グリオーマ幹細胞の網羅的エピジェネティクス解析2008

    • Author(s)
      夏目敦至
    • Organizer
      第9回日本分子脳神経外科学会
    • Place of Presentation
      京都
    • Related Report
      2008 Final Research Report
  • [Presentation] TARGETING OF GLIOMA CELLS EXPRESSING THE EGFR TYPE 3 VARIANT USING GENETICALLY ENGINEERED T-CELLS2008

    • Author(s)
      Natsume, A
    • Organizer
      The 14th Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      Sapporo
    • Related Report
      2008 Final Research Report
  • [Presentation] NEURAL STEM CELLS TRANSDUCED WITH THE IFN-beta AND CYTOSINE DEAMINASE GENES ENHANCE BYSTANDER EFFECT IN EXPERIMENTAL GLIOMAS2008

    • Author(s)
      Natsume, A
    • Organizer
      The 14th Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      Sapporo
    • Related Report
      2008 Final Research Report
  • [Presentation] THE DNA DEMETHYLATING AGENT 5- AZA-2-DEOXYCYTIDINE INDUCES THE EXPRESSION OF CANCER-TESTIS ANTIGENS IN HUMAN GLIOMAS : EPIGENETIC TARGET FOR TUMOR IMMUNOTHERAPY2008

    • Author(s)
      Natsume, A
    • Organizer
      The 17th International Conference on Brain Tumor Research and Therapy
    • Place of Presentation
      Hakodate, Japan
    • Related Report
      2008 Final Research Report
  • [Presentation] A JAPANESE MULTICENTER CLINICAL TRIAL OF INTERFERON-B AND TEMOZOLOMIDE COMBINATION THERAPY FOR HIGH-GRADE GLIOMAS : FROM BENCH TO BEDSIDE2008

    • Author(s)
      Natsume, A
    • Organizer
      The 17th International Conference on Brain Tumor Research and Therapy
    • Place of Presentation
      Hakodate, Japan
    • Related Report
      2008 Final Research Report
  • [Presentation] GLOBAL ANALYSES OF POLYCOMB MEDIATED TRANSCRPTIONALREPRESSION AND DNA METHYLATION TARGETS IN BRAIN TUMOR STEM CELLS2008

    • Author(s)
      Natsume, A
    • Organizer
      The 17th International Conference on Brain Tumor Research and Therapy
    • Place of Presentation
      Hakodate, Japan
    • Related Report
      2008 Final Research Report
  • [Presentation] ポストゲノム時代のエピジェネティクス解析 : MGMT遺伝子メチル化の定量の試み2008

    • Author(s)
      夏目敦至
    • Organizer
      第26回 日本脳腫瘍病理学会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] A JAPANESE MULTICENTER CLINICAL TRIAL OF INTERFERON-B AND TEMOZOLOMIDE COMBINATION THERAPY FOR HIGH-GRADE GLIOMAS : FROM BENCH TO BEDSIDE.2008

    • Author(s)
      Natsume A
    • Organizer
      The 17th International Conference on Brain Tum or Research and Therapy.
    • Place of Presentation
      Hakodate, Japan
    • Related Report
      2008 Annual Research Report
  • [Presentation] GLOBAL ANALYSES OF POLYCOMB MEDIATED TRANSCRPTIONALREPRESSION AND DNA METHYLATION TARGETS IN BRAIN TUMOR STEM CELLS.2008

    • Author(s)
      Natsume A
    • Organizer
      The 17th International Conference on Brain Tum or Research and Therapy.
    • Place of Presentation
      Hakodate, Japan
    • Related Report
      2008 Annual Research Report
  • [Presentation] THE DNA DEMETHYLATING AGENT 5- AZA-2-DEOXYCYTIDINE INDUCES THE EXPRESSION OF CANCER-TESTIS ANTIGENS IN HUMAN GLIOMAS : EPIGENETIC TAEGET FOR TUMOR IMMUNOTHERAPY.2008

    • Author(s)
      Natsume A
    • Organizer
      The 17th International Conference on Brain Tum or Research and Therapy.
    • Place of Presentation
      Hakodate, Japan
    • Related Report
      2008 Annual Research Report
  • [Presentation] Characteristics of AtjnpicalMenmgiomas.2008

    • Author(s)
      Natsume A
    • Organizer
      6th International Congress on Meningiomas and Cerebral Venous System.
    • Place of Presentation
      Boston, MA< USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] グリオーマ幹細胞の網羅的エピジェネティクス解析2007

    • Author(s)
      夏目敦至
    • Organizer
      第25回日本脳腫瘍学会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] バルプロ酸とDNAメチル化酵素阻害薬による2007

    • Author(s)
      夏目敦至
    • Organizer
      グリオーマの癌精巣抗原遺伝子のクロマチン構造変化第25回日本脳腫瘍学会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] Epigenetic target for cancer-testis antigen-based tumor immunotherapy2007

    • Author(s)
      夏目敦至
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] グリオーマ幹細胞の網羅的エピジェネティクス解析2007

    • Author(s)
      夏目敦至
    • Organizer
      第66回日本脳神経外科学会総会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Book] グリオーマのエピジェネティクス解析(黒岩敏彦)2009

    • Author(s)
      夏目敦至
    • Total Pages
      164
    • Publisher
      金芳堂
    • Related Report
      2008 Final Research Report
  • [Book] 脳212009

    • Author(s)
      夏目敦至
    • Total Pages
      146
    • Publisher
      金芳堂
    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.nagoya-u.ac.jp/cgrm/

    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

      http://www.med.nagoya-u.ac.jp/cgrm/

    • Related Report
      2008 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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