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悪性脳腫瘍における糖蛋白糖鎖A2G2Fを分子標的とした創薬の展開

Research Project

Project/Area Number 19659372
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionKurume University

Principal Investigator

山中 龍也  Kurume University, 先端癌治療研究センター, 教授 (20323991)

Co-Investigator(Kenkyū-buntansha) 池中 一裕  自然科学研究機構, 生理学研究所, 教授 (00144527)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2008: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2007: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywords癌 / 糖鎖 / A_2G_2F / LCAレクチン / 分子標的療法 / 脳腫瘍
Research Abstract

我々は悪性脳腫瘍組織および細胞におけるN結合型糖鎖を自動化、簡易化されたHPLCシステムを用いてN結合型糖蛋白質糖鎖の網羅的解析を行い、biantennary bigalactosylated structure with one outer arm fucosylation(Galβ1,4-GlcNAcβ1,2-Manα1,3-)(Galβ1,4-GlcNAcβ1,2-Manα1,6-)Manβ1,4-GlcNAcβ1,4-(Fucα1,6-)GlcNAc,以下A_2G_2F)という糖鎖が正常脳組織には発現せず、悪性神経膠腫組織に特異的に発現していることを明らかにした。更に、A_2G_2Fに特異的に結合するLCAレクチンが神経膠腫培養細胞および組織の腫瘍細胞と特異的に結合し、さらに腫瘍細胞にcaspase依存的アポトーシスを誘導することを明らかとした。
現在、A_2G_2Fに特異的に結合するLCAレクチン或いは抗体を用いてTargeting化学療法、免疫療法、またisotopeなどを用いてin vivoで腫瘍のimagingが可能か等、検討を進めている。また、A_2G_2Fの髄液中、血液中での値を測定することにより、神経膠腫の診断が可能かどうか検討を進めている。今後、悪性神経膠腫に特異的なマーカー分子が明らかとなり、この分子を用いた分子診断、分子標的治療の発展が期待される。LCAレクチン或は抗体に抗癌剤、immunotoxinなどを包合することにより薬剤を病巣局所に集約させ生体の有害事象を最小限に食い止められる可能性がある。また、糖鎖の異常と腫瘍の病態病理に関する知見が得られる可能性がある。糖蛋白糖鎖の研究は、脳腫瘍研究にブレークスルーを与える可能性が期待される。

Report

(3 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (43 results)

All 2009 2008 2007 Other

All Journal Article (22 results) (of which Peer Reviewed: 22 results) Presentation (12 results) Book (6 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Dendritic cell and peptide based vaccination strategies for glioma2009

    • Author(s)
      山中龍也
    • Journal Title

      Neurosurg Rev 32

      Pages: 265-273

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Management of refractory or relapsed primary central nervous system lymphoma2009

    • Author(s)
      山中龍也
    • Journal Title

      Molecular Medicine Reports 2

      Pages: 879-885

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Medical management of brain metastases from lung cancer2009

    • Author(s)
      山中龍也
    • Journal Title

      Oncol Rep 22

      Pages: 1269-1276

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular targeted therapies for glioma2009

    • Author(s)
      Yamanaka R, Saya H
    • Journal Title

      Ann Neurol 66

      Pages: 717-729

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characteristics of patients with brain metastases from lung cancer in a palliative care center2009

    • Author(s)
      Yamanaka R, Koga H, Yamamoto Y, Yamada S, Sano T, Fukushige T
    • Journal Title

      Support care cancer (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 悪性神経膠腫に対する分子標的療法(総説)2009

    • Author(s)
      山中龍也
    • Journal Title

      Brain & Nerve 61

      Pages: 177-188

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 標準治療抵抗性中枢神経系原発悪性リンパ腫に対する薬物療法(総説)2009

    • Author(s)
      山中龍也
    • Journal Title

      Brain & Nerve 61

      Pages: 1155-1164

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dendritic cell and peptide based vaccination strategies for glioma.2009

    • Author(s)
      Yamanaka R
    • Journal Title

      Neurosurg Rev. (Epub ahead of print)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 悪性神経膠腫に対する分子標的療法(総説)2009

    • Author(s)
      山中龍也
    • Journal Title

      Brain, Nerve 61(2)

      Pages: 177-188

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of EphB6 variant-derived epitope peptides recognized by cytotoxic T-lymphocytes from HLA-A24^+ malignant glioma patients.2008

    • Author(s)
      Jin M, Yamanaka R, et al.
    • Journal Title

      Oncol. Rep 19(5)

      Pages: 1277-1283

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Results of treatment of 112 cases of primary CNS lymphoma.2008

    • Author(s)
      Yamanaka R, et al.
    • Journal Title

      Jpn J Clin Oncol 38(5)

      Pages: 373-380

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] EphB6 variant-derived peptides with the ability to induce glioma-reactive cytotoxic T lymphocytes in HLA-A2+ glioma patients.2008

    • Author(s)
      Jin M, Yamanaka R, et al.
    • Journal Title

      Cancer Sci 99(8)

      Pages: 1656-1662

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proteomic Characterization of Primary CNS Diffuse Large B-cell Lymphomas.2008

    • Author(s)
      Li J, Yamanaka R, et al.
    • Journal Title

      J Neurosurg 109(3)

      Pages: 536-546

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] EphA4 promotes cell proliferation and migration through a novel EphA4-FGFRl signaling pathway in the human glioma U251 cell line.2008

    • Author(s)
      Fukai J, Yamanaka R, et al.
    • Journal Title

      Mol Cancer Ther. 7(9)

      Pages: 2768-2678

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cellular and peptide based immnunotherapeutic approaches for glioma.2008

    • Author(s)
      Yamanaka R
    • Journal Title

      Trends Mol Med 14(5)

      Pages: 228-235

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Kinesin superfamily protein-derived peptides with the ability to induce glioma-reactive cytotoxic T lymphocytes in HLA-A24^+ glioma patients2007

    • Author(s)
      Harada M, Ishihara Y, Itoh K and Yamanaka R
    • Journal Title

      Ohcol Rep 17

      Pages: 629-636

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immuno-chemotherapy with a Combination of Rituximab, Methotrexate, Pirarubicin and Procarbazine for Patients with Primary CNS Lymphoma-A preliminary report2007

    • Author(s)
      Yamanaka R, Homma J, Sano M, Tsuchiya N, Yajima N, Shinbo Y, Hasegawa A. Onda K, and Tanaka R
    • Journal Title

      Leukemia Lymphoma 48

      Pages: 1019-1022

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Salvage Therapy and Late Neurotoxicity in Patients with Recurrent Primary CNS Lymphoma treated with a Modified ProMACE-MOPP Hybrid Regimen2007

    • Author(s)
      Yamanaka R, Shinbo Y, Sano M, Homma J, Tsuchiya N, Yajima N, Tamura T, Hondoh H, Takahashi H, Morii K, Onda K, and Tanaka R
    • Journal Title

      Leukemia Lymphoma 48

      Pages: 1119-1126

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Salvage Immuno-Chemotherapy with a Combination of Rituximab, High Dose Cytarabine, Mitoxantrone and Dexamethasone for Patients with Primary CNS Lymphoma: A Preliminary Study2007

    • Author(s)
      Yamanaka R, Hoinma J, Sano M, Tsuchiya N, Yajima N, Takahashi H, Shinbo Y, Hasegawa A, Saitoh T and Tanaka R
    • Journal Title

      Leukemia Lymphoma 48

      Pages: 1429-1433

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peptide-based immunotherapeutic approaches to glioma-Review2007

    • Author(s)
      Yamanaka R, Itoh K
    • Journal Title

      EXPERT OPIN BIOL TH 7

      Pages: 645-649

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 悪性神経膠腫に対するペプチド療法(総説)2007

    • Author(s)
      山生 龍也、伊東 恭悟
    • Journal Title

      BRAIN and NERVE 59

      Pages: 251-261

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 悪性脳腫瘍に対する分子標的治療開発に向けたトランスレーショナル研究2007

    • Author(s)
      山中 龍也
    • Journal Title

      久留米医学会雑誌 70

      Pages: 185-192

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 当院緩和ケア病棟における肺癌脳転移55症例の臨床的検討2009

    • Author(s)
      山中龍也、古賀初代、山本洋介、山田信一、佐野智美、福重哲志
    • Organizer
      第14回日本緩和医療学会学術大会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] 当院緩和ケア病棟における肺癌脳転移55症例の臨床的検討2009

    • Author(s)
      山中龍也、福重哲志
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] 包括的遺伝子発現情報を基にした悪性神経膠腫患者の予後を予測する遺伝子の探索2008

    • Author(s)
      山中龍也, 他
    • Organizer
      第6回日本臨床腫瘍学会
    • Place of Presentation
      福岡
    • Related Report
      2008 Annual Research Report
  • [Presentation] Nleningiomaを合併し、ACNU, Temozolomideに著明に反応したradiation induced gliomaの1例2008

    • Author(s)
      近貴志, 山中龍也, 他
    • Organizer
      第26回日本脳腫瘍病理学会
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report
  • [Presentation] (シンポジウム)脳神経外科における臨床腫瘍認定医の育成プログラム-がん薬物療法専門医・癌治療認定医の立場からの専門医教育2008

    • Author(s)
      山中龍也
    • Organizer
      第67回日本脳神経外科学会総会
    • Place of Presentation
      盛岡
    • Related Report
      2008 Annual Research Report
  • [Presentation] (ワークショップ)高速液体クロマトグラフィーを用いた神経膠芽腫組織内N-結合型糖タンパク質糖鎖の分離、解析2008

    • Author(s)
      山中龍也, 他
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] (ワークショップ)テーラーメイド癌ペプチドワクチン臨床試験の生存解析 : 475症例でのアップデート2008

    • Author(s)
      峯孝志, 山中龍也, 他
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] 包括的遺伝子発現情報を基にした悪性神経膠腫患者の予後を予測する遺伝子の探索2008

    • Author(s)
      山中龍也, 他
    • Organizer
      第46回日本癌治療学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] 下垂体腺腫に対する照射22年後にmeningioma, 30年後にgliomaを発症した1例2008

    • Author(s)
      近貴志, 山中龍也, 他
    • Organizer
      第26回日本脳腫瘍学会
    • Place of Presentation
      松山
    • Related Report
      2008 Annual Research Report
  • [Presentation] Immunologic and clinical effects of personalized selection of peptide vaccines in HLA-A2 positive patients with advanced cancer.2008

    • Author(s)
      Noguchi M, Yamanaka R, et al.
    • Organizer
      The 44^<nd> Meeting of the American Society of Clinical Oncology
    • Place of Presentation
      Chicago
    • Related Report
      2008 Annual Research Report
  • [Presentation] Isolation and Characterization of an N-Linked Oligosaccharide That Is Increased in Glioblastoma Tissue and Cell Line.2008

    • Author(s)
      Yamanaka R, et al.
    • Organizer
      The 13^<th> Meeting of the Society for Neuro-Oncology
    • Place of Presentation
      Las Vegas
    • Related Report
      2008 Annual Research Report
  • [Presentation] Identification of expressed genes characterizing long-term survival in malinant glioma patients2007

    • Author(s)
      Yamanaka R and Nishio K
    • Organizer
      The 12th Meeting of the Society for Neuro-Oncology
    • Place of Presentation
      Dallas,Texas
    • Related Report
      2007 Annual Research Report
  • [Book] Immunotherapeutic approach for malignant glioma by alpha viruses as positive strand RNA viruses. pp125-140, In Therapeutic ribonucleic acids in brain tumors(Erdmann VA, Reifenberger G, Barciszewski J(eds.))2009

    • Author(s)
      Yamanaka R
    • Total Pages
      16
    • Publisher
      Springer
    • Related Report
      2009 Annual Research Report
  • [Book] Immunotherapeutic approach for malignant glioma by alpha viruses as positive strand RNA viruses. In Therapeutic Ribonucleic Acids in Brain Tumors2009

    • Author(s)
      Yamanaka R
    • Publisher
      Springer(In press)
    • Related Report
      2008 Annual Research Report
  • [Book] Dendritic cell vaccine. In Glioma : Immunotherapeutic approachs.2009

    • Author(s)
      Yamanaka R, Kajiwara K
    • Publisher
      Landes Bioscience(In press)
    • Related Report
      2008 Annual Research Report
  • [Book] Alpha Viruses. In Viral Therapy of Cancer.2008

    • Author(s)
      Yamanaka R
    • Publisher
      Wiley
    • Related Report
      2008 Annual Research Report
  • [Book] がん看護実践シリーズ、脳腫瘍2007

    • Author(s)
      山中 龍也
    • Total Pages
      7
    • Publisher
      メジカルフレンド社
    • Related Report
      2007 Annual Research Report
  • [Book] Dendritic cell vaccine. In Yamanaka R(ed.), Glioma : Immunotherapeutic approaches

    • Author(s)
      Yamanaka R, Kajiwara K
    • Publisher
      Landes Bioscience
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://research.kurume-u.ac.jp/K10FRM.php

    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] HLA-A24またはHLA-A2分子結合性EphB6変異体由来ペプチド2008

    • Inventor(s)
      山田亮, 伊東恭悟, 七條茂樹, 山中龍也
    • Industrial Property Rights Holder
      学校法人久留米大学
    • Filing Date
      2008-08-08
    • Related Report
      2008 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] HLA-A24またはHLA-A2分子結合性EphB6変異体由来ペプチド

    • Inventor(s)
      山田 亮, 伊東 恭悟, 七條 茂樹, 山中 龍也
    • Industrial Property Rights Holder
      学校法人久留米大学
    • Industrial Property Number
      2007-000824
    • Related Report
      2007 Annual Research Report

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

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