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Anti-angiogenic therapy for brain tumors targeting neuro-vascular wiring molecules

Research Project

Project/Area Number 15H04947
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurosurgery
Research InstitutionUniversity of Tsukuba

Principal Investigator

TAKANO SHINGO  筑波大学, 附属病院, 病院講師 (50292553)

Co-Investigator(Kenkyū-buntansha) 加藤 幸成  東北大学, 医学系研究科, 教授 (00571811)
久保田 義顕  慶應義塾大学, 医学部(信濃町), 教授 (50348687)
山下 年晴  筑波大学, 医学医療系, 助教 (50400677)
依馬 正次  滋賀医科大学, 動物生命科学研究センター, 教授 (60359578)
松田 和郎  獨協医科大学, 医学部, 准教授 (80444446)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords神経膠腫 / 神経血管ワイアリング / 血管新生抑制療法 / lenalidomide / chetomin / 低酸素誘導因子 / グリオーマ / slit2 / 血管新生抑制 / 神経血管ワイヤリング / 血管新生 / 血管内皮細胞 / 管腔形成 / siRNA / 脳腫瘍増殖制御 / in vivo imaging / Slit2 / 免疫組織化学 / RT-PCR解析 / western解析
Outline of Final Research Achievements

In order to make baseline of new anti-angiogenic therapy for glioblastoma, we focused on neurovascularar wiring factors. Among neurovascular wiring factors, we found that slit2 expressed in glioblastoma associated with marked angiogenesis and promoted glioblastoma induced angiogenesis using glioblastoma tissues and cell lines. On therapeutic point, lenalidomide inhibited slit2 mRNA expression and chetomin inhibited cell growth under hypoxia and HIF-1α protein expression. Combined therapy with inhibitors of neurovascular wiring factor, slit2 and HIF-1α promise growth inhibition for glioblastoma.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (29 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (15 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 12 results,  Open Access: 5 results,  Acknowledgement Compliant: 7 results) Presentation (13 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Int'l Joint Research] エモリー大学脳神経外科(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] MyD88 Mutation in Elderly Predicts Poor Prognosis in Primary Central Nervous System Lymphoma: Multi-Institutional Analysis2018

    • Author(s)
      Takano Shingo、Hattori Keiichiro、Ishikawa Eiichi、Narita Yoshitaka、Iwadate Yasuo、Yamaguchi Fumio、Nagane Motoo、Akimoto Jiro、Oka Hidehiro、Tanaka Satoshi、Sakata Mamiko、Matsuda Masahide、Yamamoto Tetsuya、Chiba Shigeru、Matsumura Akira
    • Journal Title

      World Neurosurgery

      Volume: 112 Pages: e69-e73

    • DOI

      10.1016/j.wneu.2017.12.028

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic analysis of patients who underwent gross total resection of newly diagnosed glioblastoma2018

    • Author(s)
      Matsuda Masahide、Kohzuki Hidehiro、Ishikawa Eiichi、Yamamoto Tetsuya、Akutsu Hiroyoshi、Takano Shingo、Mizumoto Masashi、Tsuboi Koji、Matsumura Akira
    • Journal Title

      Jornal of Clinical Neuroscience

      Volume: 50 Pages: 172-176

    • DOI

      10.1016/j.jocn.2018.01.009

    • NAID

      120007134222

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 膠芽腫に対する血管新生抑制療法の課題と対処:血管cooptionとmimicry2018

    • Author(s)
      高野晋吾
    • Journal Title

      Jpn J Neurosurg

      Volume: 印刷中

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of bevacizumab therapy in recurrent malignant gliomas in relation to the prior recurrence pattern or tumor location2017

    • Author(s)
      Matsuda Masahide、Ishikawa Eiichi、Yamamoto Tetsuya、Akutsu Hiroyoshi、Takano Shingo、Matsumura Akira
    • Journal Title

      Journal of Clinical Neuroscience

      Volume: 40 Pages: 115-119

    • DOI

      10.1016/j.jocn.2017.02.025

    • NAID

      120007134417

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Assessment of PD-1 positive cells on initial and secondary resected tumor specimens of newly diagnosed glioblastoma and its implications on patient outcome2017

    • Author(s)
      Miyazaki Tsubasa、Ishikawa Eiichi、Matsuda Masahide、Akutsu Hiroyoshi、Osuka Satoru、Sakamoto Noriaki、Takano Shingo、Yamamoto Tetsuya、Tsuboi Koji、Matsumura Akira
    • Journal Title

      Journal of Neuro-Oncology

      Volume: 133 Issue: 2 Pages: 277-285

    • DOI

      10.1007/s11060-017-2451-7

    • NAID

      120007128861

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical significance of disease-specific MYD88 mutations in circulating DNA in primary central nervous system lymphoma2017

    • Author(s)
      Hattori Keiichiro、Sakata-Yanagimoto Mamiko、Suehara Yasuhito、Yokoyama Yasuhisa、Kato Takayasu、Kurita Naoki、Nishikii Hidekazu、Obara Naoshi、Takano Shingo、Ishikawa Eiichi、Matsumura Akira、Hasegawa Yuichi、Chiba Shigeru
    • Journal Title

      Cancer science

      Volume: 109 Issue: 1 Pages: 225-230

    • DOI

      10.1111/cas.13450

    • NAID

      120007134545

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The antiangiogenic role of soluble-form VEGF receptor (sFlt1) in malignant gliomas.2017

    • Author(s)
      6.Takano S, Ishikawa E, Matsuda M, Sakamoto N, Akutsu H, Yamamoto T, Matsumura A
    • Journal Title

      International Journal of Oncology

      Volume: 50 Issue: 2 Pages: 515-524

    • DOI

      10.3892/ijo.2016.3810

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] mmunohistochemistry on IDH 1/2, ATRX, p53 and Ki-67 substitute molecular genetic testing and predict patient prognosis in grade III adult diffuse gliomas.2016

    • Author(s)
      Takano S, Ishikawa E, Sakamoto N, Matsuda M, Akutsu H, Noguchi M, Kato Y, Yamamoto T, Matsumura A
    • Journal Title

      Brain Tumor Pathology

      Volume: 33 Issue: 2 Pages: 107-116

    • DOI

      10.1007/s10014-016-0260-x

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 基礎研究と臨床試験からみた悪性グリオーマにおけるベバシズマブ. 癌と化学療法 Current Organ Topics: 脳腫瘍―グリオーマ2016

    • Author(s)
      高野晋吾
    • Journal Title

      Gan to Kagaku Ryoho

      Volume: 43 Pages: 694-701

    • Related Report
      2016 Annual Research Report
    • Acknowledgement Compliant
  • [Journal Article] 退形成性星細胞腫. 脳腫瘍学-基礎研究と臨床研究の進歩-2016

    • Author(s)
      高野晋吾
    • Journal Title

      日本臨床 74: suppl 7, 377-386,

      Volume: 74, suppl 7 Pages: 377-386

    • Related Report
      2016 Annual Research Report
    • Acknowledgement Compliant
  • [Journal Article] グリオーマの免疫染色定量評価2016

    • Author(s)
      高野晋吾、松田真秀、石川栄一、坂本規影、阿久津博義、木野弘善、山本哲哉、松村 明
    • Journal Title

      Neuro-Oncologyの進歩

      Volume: 23-1 Pages: 14-20

    • NAID

      130005150139

    • Related Report
      2016 Annual Research Report
    • Acknowledgement Compliant
  • [Journal Article] Diagnostic advantage of double immunohistochemistry using two mutation-specific anti-IDH antibodies (HMab-1 and MsMab-1) in gliomas.2015

    • Author(s)
      Takano S, Kato Y, Yamamoto T, Liu X, Ishikawa E, Kaneko MK, Ogasawara S, Matsuda M, Noguchi M, Matsumura A.
    • Journal Title

      Brain Tumor Pathol.

      Volume: 32 Issue: 3 Pages: 169-175

    • DOI

      10.1007/s10014-015-0214-8

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Improvement of long-term results with neoadjuvant chemotherapy and radiotherapy for central nervous system germinoma2015

    • Author(s)
      Takano S, Yamamoto T, Ishikawa E, Akutsu H, Nakai K, Matsuda M, Muroi A, Shibata Y, Mizumoto M, Tsuboi K, Matsumura A
    • Journal Title

      World Neurosurgery

      Volume: 84 Issue: 3 Pages: 846-854

    • DOI

      10.1016/j.wneu.2015.06.029

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neuroendoscopy followed by radiotherapy in cystic craniopharyngiomas-a long-term follow-up2015

    • Author(s)
      Takano S, Akutsu H, Mizumoto M, Yamamoto T, Tsuboi K, Matsumura A
    • Journal Title

      World Neurosurgery

      Volume: 84 Issue: 5 Pages: 1305-1315

    • DOI

      10.1016/j.wneu.2015.06.022

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A high-sensitive HMab-2 specifically detects IDH1-R132H, the most common IDH mutation in gliomas2015

    • Author(s)
      Fujii Y, Ogasawara S, Oki H, Liu X, Kaneko MK, Takano S, Kato Y
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 466 Issue: 4 Pages: 733-739

    • DOI

      10.1016/j.bbrc.2015.09.070

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] グリオーマの血管新生と治療2017

    • Author(s)
      高野晋吾
    • Organizer
      第37回脳神経外科コングレス
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] MyD88 mutation in the elderly predicts a poor prognosis in primary CNS lymphoma: multi-institutional analysis2017

    • Author(s)
      Takano S, Hattori K, Ishikawa E, Narita Y, Iwadate Y, Yamaguchi F, Nagane M, Akimoto J, Oka H, Tanaka S, Sakata M, Matsuda M, Yamamoto T, Chiba S, Matsumura A
    • Organizer
      The 14th Asian Society for Neuro-Oncology Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 低酸素状態でのグリオーマ血管新生の問題点と対策2017

    • Author(s)
      高野晋吾、石川栄一、松田真秀、阿久津博義、鶴淵隆夫、益子良太、松村 明
    • Organizer
      第35回 日本脳腫瘍学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 膠芽腫血管新生抑制の治療標的としての低酸素誘導性因子の重要性2017

    • Author(s)
      高野晋吾, 石川 栄一, 松田 真秀, 益子 良太, 阿久津 博義, 松村 明
    • Organizer
      第76回脳神経外科学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 中枢神経原発リンパ腫の遺伝子変異と予後解析2017

    • Author(s)
      高野晋吾、服部圭一郎、成田善孝、岩立康男、山口文雄、永根基雄、秋元治朗、岡秀宏、田中聡、石川栄一、山本哲哉、坂田麻美子、千葉滋、松村明
    • Organizer
      第35回日本脳腫瘍病理学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 神経血管ワイアリング分子 Slit2のグリオーマ血管新生における役割2016

    • Author(s)
      高野晋吾、石川栄一、坂本規影、松田真秀、山本哲哉、松村 明
    • Organizer
      第34回脳腫瘍病理学会
    • Place of Presentation
      東京都、江東区、東京コンファレンスセンター・有明
    • Related Report
      2016 Annual Research Report
  • [Presentation] グリオーマの血管新生と予後.2016

    • Author(s)
      高野晋吾、石川栄一、松田真秀、上月暎浩、増田洋亮、津田恭二、山本哲哉、松村 明:
    • Organizer
      第75回脳神経外科学会総会
    • Place of Presentation
      福岡県、福岡市、福岡国際会議場
    • Related Report
      2016 Annual Research Report
  • [Presentation] 神経血管ワイアリング分子 Slit2のグリオーマ血管新生における役割2016

    • Author(s)
      高野晋吾、石川栄一、松田真秀、坂本規影、上月暎浩、山本哲哉、松村 明
    • Organizer
      第34回脳腫瘍学会
    • Place of Presentation
      山梨県、甲府市、甲府冨士屋ホテル
    • Related Report
      2016 Annual Research Report
  • [Presentation] 分子診断によるgrade IIIグリオーマの予後解析2015

    • Author(s)
      高野晋吾、山本哲哉、石川栄一、坂本則影、松田真秀、中井 啓、阿久津博義、加藤幸成、松村 明
    • Organizer
      第33回日本脳腫瘍病理学会
    • Place of Presentation
      全日空ホテル(香川県、高松市)
    • Related Report
      2015 Annual Research Report
  • [Presentation] 悪性神経膠腫におけるポドプラニン発現・IDH変異・Aktシグナルによる予後解析.2015

    • Author(s)
      高野晋吾、石川栄一、松田真秀、加藤幸成、山本哲哉、松村 明
    • Organizer
      第16回分子脳神経外科学会
    • Place of Presentation
      アクトシティ浜松(静岡県、浜松市)
    • Related Report
      2015 Annual Research Report
  • [Presentation] Podoplanin expression combined with IDH mutation as a prognostic factor with high grade gliomas.2015

    • Author(s)
      高野晋吾、石川栄一、松田真秀、金子美華、加藤幸成
    • Organizer
      第74回日本癌学会総会
    • Place of Presentation
      名古屋国際会議場(愛知県、名古屋市)
    • Related Report
      2015 Annual Research Report
  • [Presentation] 血管内皮増殖因子(VEGF)/低酸素誘導因子(HIF1)発現はIDH変異とは独立したグリオーマの予後因子である2015

    • Author(s)
      高野晋吾、石川栄一、松田真秀、中井 啓、阿久津博義、山本哲哉、加藤幸成、松村 明.
    • Organizer
      第74回日本脳神経外科学会総会
    • Place of Presentation
      ロイトン札幌(北海道、札幌市)
    • Related Report
      2015 Annual Research Report
  • [Presentation] 悪性神経膠腫に対するベバシズマブ:基礎研究から臨床試験.2015

    • Author(s)
      高野晋吾
    • Organizer
      第74回日本脳神経外科学会総会
    • Place of Presentation
      ロイトンン札幌(北海道、札幌市)
    • Related Report
      2015 Annual Research Report
    • Invited

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Published: 2015-04-16   Modified: 2019-03-29  

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