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Development of new anti-angiogenic drugs for non-VEGF pathway using drug repositioning

Research Project

Project/Area Number 18K08944
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionOkayama University

Principal Investigator

Michiue Hiroyuki  岡山大学, 中性子医療研究センター, 准教授 (20572499)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords抗血管新生療法 / 抗血管背陰性薬 / 脳腫瘍幹細胞 / 膠芽腫 / VEGF / 既存薬再開発 / 血液脳関門 / 血管内皮細胞 / 悪性脳腫瘍 / 腫瘍血管 / 分化 / 虚血 / 薬剤スクリーニング / ドラッグリポジショニング / 抗血管新生薬 / 集学的治療 / アバスチン / 低酸素
Outline of Final Research Achievements

The current treatments for malignant brain tumors are mainly surgery, radiation therapy, and chemotherapy, and in addition to this, multidisciplinary treatment by combination therapy such as immunotherapy is performed, but the prognosis is previously poor.
Among them, the concept of anti-angiogenic therapy for malignant tumors has been advocated since the 1970s, and the development of bevacizumab, an anti-human VEGF monoclonal antibody, has been shown to be effective in colorectal cancer, ovarian cancer, lung cancer, etc. However, no prognosis-prolonging effect was observed in malignant tumors. This time, we have identified the cause of this treatment resistance and identified a new effect by using it in combination with a new drug.

Academic Significance and Societal Importance of the Research Achievements

悪性腫瘍に栄養や酸素などを供給する腫瘍血管の形成をブロックして、腫瘍を兵糧攻めにする抗血管新生療法は、概念として素晴らしいものである。膠芽腫(悪性神経膠腫)に対する抗血管新生療法は、臨床試験において有効性を示さなかった。これはこの治療法の概念を否定するものでなく、使用したVEGFR/VEGF-R経路阻害薬の抗VEGF抗体だけでは不十分であるとの仮説を立て、本研究の着想に至った。我々は、治療抵抗性の原因となると考えた脳腫瘍幹細胞由来の新たな血管を攻撃する薬剤の開発研究を行った。またこの薬剤がどのような働きをするかを解明し、今後の研究発展へ繋げた。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (27 results)

All 2021 2020 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (19 results) (of which Int'l Joint Research: 6 results,  Invited: 8 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Complementary Leucine Zippering System for Effective Intracellular Delivery of Proteins by Cell-Penetrating Peptides2021

    • Author(s)
      Mizuki Kitamatsu, Hiroki Yuasa, Takashi Ohtsuki, Hiroyuki Michiue
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 33 Pages: 116036-116041

    • DOI

      10.1016/j.bmc.2021.116036

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Self-assembling A6K peptide nanotubes as a mercaptoundecahydrododecaborate (BSH) delivery system for boron neutron capture therapy (BNCT)2021

    • Author(s)
      Michiue H, Kitamatsu M, Fukunaga A, Tsuboi N, Fujimura A, Matsushita H, Igawa K, Kasai T, Kondo N, Matsui H, Furuya S.
    • Journal Title

      J Control Release.

      Volume: 330 Pages: 788-796

    • DOI

      10.1016/j.jconrel.2020.11.001

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improvement of Water Solubility of Mercaptoundecahydrododecaborate (BSH)-Peptides by Conjugating with Ethylene Glycol Linker and Interaction with Cyclodextrin2021

    • Author(s)
      Kitamatsu Mizuki、Nakamura-Tachibana Ayaka、Ishikawa Yoshimichi、Michiue Hiroyuki
    • Journal Title

      Processes

      Volume: 9 Issue: 1 Pages: 167-167

    • DOI

      10.3390/pr9010167

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A leucine zipper-based peptide hybrid delivers functional Nanog protein inside the cell nucleus.2019

    • Author(s)
      Yoshiyuki Hakata, Hiroyuki Michiue, Takashi Ohtsuki, Masaaki Miyazawa and Mizuki Kitamatsu
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 29 Issue: 7 Pages: 878-881

    • DOI

      10.1016/j.bmcl.2019.02.004

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Boron Neutron Capture Therapy Combined with Early Successive Bevacizumab Treatments for Recurrent Malignant Gliomas ? A Pilot Study2018

    • Author(s)
      SHIBA Hiroyuki、TAKEUCHI Koji、HIRAMATSU Ryo、FURUSE Motomasa、NONOGUCHI Naosuke、KAWABATA Shinji、KUROIWA Toshihiko、KONDO Natsuko、SAKURAI Yoshinori、SUZUKI Minoru、ONO Koji、OUE Shiro、ISHIKAWA Eiichi、MICHIUE Hiroyuki、MIYATAKE Shin-Ichi
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 58 Issue: 12 Pages: 487-494

    • DOI

      10.2176/nmc.oa.2018-0111

    • NAID

      130007531206

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oxytocin inhibits corticosterone-induced apoptosis in primary hippocampal neurons.2018

    • Author(s)
      Hein Min Latt, Hiroaki Matsushita, Miku Morino, Yuuri Koga, Hiroyuki Michiue, Teiichi Nishiki, Kazuhito Tomizawa, Hideki Matsui
    • Journal Title

      Neuroscience

      Volume: - Pages: 383-389

    • DOI

      10.1016/j.neuroscience.2018.03.025

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] グルコース輸送体標的ホウ素薬剤による悪性脳腫瘍BNCTの新しい戦略2020

    • Author(s)
      道上宏之
    • Organizer
      第79回日本脳神経外科学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] グルコース輸送体を標的とした新規ホウ素製剤開発へ向けて2020

    • Author(s)
      道上宏之
    • Organizer
      令和2年度京都大学複合原子力科学研究所専門研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 「ホウ素薬剤開発の現状 ~基礎研究より橋渡し研究へ向けて~2020

    • Author(s)
      道上宏之
    • Organizer
      令和2年度 第1回量子医療研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 両親媒性ペプチドを用いたホウ素ペプチド創薬2020

    • Author(s)
      道上宏之
    • Organizer
      「ナノ・バイオ融合によるエネルギー集積・高度利用研究拠点形成」   シンポジウム 「ペプチドの新たな未来へ向けて」
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] The role of calcineurin in controlling cell function in hair generation2020

    • Author(s)
      Hiroyuki Michiue
    • Organizer
      National Symposium and Workshop in Anti-Aging Medicine
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Translational research in hair generation from lab to life2020

    • Author(s)
      Hiroyuki Michiue
    • Organizer
      National Symposium and Workshop in Anti-Aging Medicine
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] New drug discovery with drug re-positioning system toward GBM treatment2019

    • Author(s)
      Hiroyuki Michiue, Nobushige Tsuboi, Keiichiro Hayashi, Hideki Matsui, Kazuhiko Kurozumi
    • Organizer
      2019 Society of Neuro-Oncology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] New peptide Drug Delivery System with BSH toward future BNCT clinical application2019

    • Author(s)
      Hiroyuki Michiue, Asami Fukunaga, Mizuki Kitamatsu, Natsuko Kondo, Yoshinori Sakurai, Atsushi Fujimura, Kazuyo Igawa, Hideki Matsui, Shuichi Furuya
    • Organizer
      10th Young Reserchers BNCT Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ペプチドDDSを用いた新規ホウ素 薬剤製剤化への取り組み2019

    • Author(s)
      道上宏之
    • Organizer
      第3回NTRCシンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] The cell biological evaluation with Nagoya University BNCT system2019

    • Author(s)
      道上宏之, 井川和代, 古矢修一, 市川康明, 吉橋幸子, 瓜谷章, 渡辺賢一, 鬼柳善明, 土田一輝
    • Organizer
      第16回日本中性子捕捉療法学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ホウ素中性子捕捉療法(BNCT)のメラノーマ治療における位置づけ~BNCTの基礎より最新の研究まで~2018

    • Author(s)
      道上宏之
    • Organizer
      第6回岡山メラノーマ治療研究会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 再発メラノーマに対するBNCTを含めた新規集学的治療の取り組み2018

    • Author(s)
      道上宏之
    • Organizer
      第22回日本がん免疫学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] ペプチドDDSを用いた新規ホウ素薬剤の構築2018

    • Author(s)
      道上宏之 福永麻美 北松瑞生  近藤夏子  櫻井良憲  藤村篤史  井川和代  松井秀樹  古矢修一
    • Organizer
      第15回日本中性子捕捉療法学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] New multidisciplinary treatment with Boron Neutron Capture Therapy (BNCT) against melanoma2018

    • Author(s)
      道上宏之
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] New self-assembling peptide Drug Delivery System with BSH toward clinical application2018

    • Author(s)
      道上宏之
    • Organizer
      18th International Congress on Neutron Capture Therapy (ICNCT-18)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] New A6k boron drug delivery system for clinical application of Boron Neutron Capture Therapy (BNCT)2018

    • Author(s)
      道上宏之
    • Organizer
      2018 Annual Meeting and Education Day of the Society for Neuro-Oncology.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] BNCTを用いた新規岡山大学メラノーマ集学的治療へ向けた取り組み2018

    • Author(s)
      道上宏之
    • Organizer
      第2回中性子医療研究センターシンポジウム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] BNCT治療の現実とこれから2018

    • Author(s)
      道上宏之
    • Organizer
      第2回中性子医療研究センターシンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] 脳腫瘍幹細胞由来の腫瘍血管を標的とした新規抗血管新生療法の開発2018

    • Author(s)
      道上宏之
    • Organizer
      第36回日本脳腫瘍学会学術集会
    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] グルコース結合ホウ素薬剤2020

    • Inventor(s)
      道上宏之
    • Industrial Property Rights Holder
      道上宏之
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] グルコース結合ホウ素薬剤2020

    • Inventor(s)
      道上宏之 高口豊
    • Industrial Property Rights Holder
      道上宏之 高口豊
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-051323
    • Filing Date
      2020
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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