tumor specific new boron agent for BNCT

• Project/Area Number: 24390293
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Okayama University
• Principal Investigator: MATSUI Hideki 岡山大学, 医歯(薬)学総合研究科, 教授 (30157234)
• Co-Investigator(Kenkyū-buntansha): MICHIUE Hiroyuki 岡山大学, 大学院医歯薬学総合研究科, 助教 (20572499)
• Co-Investigator(Renkei-kenkyūsha): ONO Koji 京都大学, 原子炉実験所中性子医療高度化研究部門, 教授 (90122407) ; MIYATAKE Shin-ichi 大阪医科大学, 先端医療開発部門, 教授 (90209916)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2012: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
• Keywords: がん / ホウ素中性子捕捉療法 / 粒子線治療 / 悪性脳腫瘍 / ホウ素薬剤研究 / 細胞内導入 / ホウ素製剤 / リポソーム / ペプチド / 細胞膜通過ペプチド / テーラーメイド / 難治性がん / 腫瘍徳的ペプチド / タンパク質導入 / タンパク質セラピー法 / ポリアルギニン

Outline of Final Research Achievements

New anti-cancer therapy with boron neutron capture therapy (BNCT) is based on the nuclear reaction of boron-10 with neutron irradiation. In BNCT clinical trial, two boron compounds, BPA (boronophenylalanine) and BSH (sodium borocaptate), were used for BNCT. BPA is taken up into cells through amino acid transporters that are expressed highly in almost all malignant cells, but BSH cannot pass through the cell membrane and remains outside the cell. To overcome this disadvantage of BSH in BNCT, we used a cell-penetrating peptide system for transduction of BSH. CPP (cell-membrane penetrating peptide) is very common peptide domains that transduce many physiologically active substances into cells in vitro and in vivo. BSH-fused CPPs can penetrate the cell membrane and localize inside a cell. BSH-CPP is one of the most promising boron agent in next generation BNCT.

Research Products

• [Journal Article] Novel leucine zipper motif-based hybrid peptide delivers functional peptide cargo inside cells. (2015)
  • Author(s): Hakata, Y., S. Tsuchiya, H. Michiue, T. Ohtsuki, H. Matsui, M. Miyazawa, and M. Kitamatsu
  • Journal Title: Chem. Comm. Volume: 51 Issue: 2 Pages: 413-416
  • DOI: 10.1039/c4cc07459a
  • Peer Reviewed / Open Access
• [Journal Article] Cdk5rap1-mediated 2-methylthio modification of mitochondrial tRNAs governs protein translation and contributes to myopathy in mice and humans. (2015)
  • Author(s): Wei FY, Zhou B, Suzuki T, Miyata K, Ujihara Y, Horiguchi H, Takahashi N, Xie P, Michiue H, Fujimura A, Kaitsuka T, Matsui H, Koga Y, Mohri S, Suzuki T, Oike Y, Tomizawa K.
  • Journal Title: Cell Metab Volume: 21 Issue: 3 Pages: 413-6
  • DOI: 10.1016/j.cmet.2015.01.019
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The acceleration of boron neutron capture therapy using multi-linked mercaptoundecahydrododecaborate (BSH) fused cell-penetrating peptide. (2014)
  • Author(s): Michiue H, Sakurai Y, Kondo N, Kitamatsu M, Bin F, Nakajima K, Hirota Y, Kawabata S, Nishiki T, Ohmori I, Tomizawa K, Miyatake S, Ono K, Matsui H.
  • Journal Title: Biomaterials. Volume: 35 Issue: 10 Pages: 3396-3405
  • DOI: 10.1016/j.biomaterials.2013.12.055
  • Peer Reviewed
• [Journal Article] A Protein Transduction Method using 01igo-Arginine (3R) For the Delivery of Transcription Factors into Cell Nuclei (2012)
  • Author(s): Hi tsuda T, Michiue H. Ki tamatsu M, Fuj iraura A, Wang F, Yamaraoto T, Han X-J, Tazawa H, Uneda A, Ohmori l, Nishiki T, Tomizaia T, Matsui H.
  • Journal Title: Biomaterials Volume: 33 Pages: 4665-4672
  • Peer Reviewed
• [Journal Article] Combining Poly-Arginine with the Hydrophobic Counter-anion 4-(1-Pyrenyl)-Butyric Acid for Protein Transduction in Transdermal Delivery (2012)
  • Author(s): Candan G, Michiue H, Ishikawa S, Fuj imura A, Hayashi K. Uneda A, Mori A, Ohmori l, Nishiki T, Matsui H, Tomizawa K
  • Journal Title: Biomaterials Volume: 33(Epub 2012 Jun 26.) Issue: 27 Pages: 6468-6475
  • DOI: 10.1016/j.biomaterials.2012.04.056
  • NAID: 120005232488
  • Peer Reviewed
• [Journal Article] CACNAlA variants may modify the epilptic phenotype of Dravet syndrome (2012)
  • Author(s): Ohmori l, Ouchida M, Kobayashi K, Jitsuraori Y, Mori A, Michiue H, Nishiki T, Ohtsuka Y, Matsui H ,
  • Journal Title: Neurobiology of Disease Volume: 50 Pages: 209-217
  • Peer Reviewed
• [Journal Article] RGS2 mediates the anxiolytic fffect of oxytocin. (2012)
  • Author(s): Okimoto N, Bosch OJ, Slattery DA. Pflaum K, Matsushita H, Wei F-Y. Ohmor i M, Nishiki T, Ohmor i l, Hiramatsu Y, Matsui H, Neumann ID. Tomizawa K.
  • Journal Title: Brain Res Volume: 1, 453 Pages: 26-33
  • Peer Reviewed
• [Journal Article] Antidepressant-like effect of sildenafil through oxytocin-dependent cyelic AMP response element-binding protein phosphorylation, (2012)
  • Author(s): Matsushita H, Matsuzaki M, Han XJ. Nishiki T, Ohmori l, Michiue H, Matsui H, Tomizawa K.
  • Journal Title: Neuroscience Volume: 200 Pages: 13-18
  • Peer Reviewed
• [Journal Article] Ca2+-independent syntax in binding to the C2B effector region of synaptotagmin. (2012)
  • Author(s): Masumoto T, Suzuki K, Ohmori I, Michiue H, Tomizawa K, Fujimura A, Nishiki T, Matsui H.
  • Journal Title: Hoi Cell Neurosci Volume: 49 Pages: 1-8
  • Peer Reviewed
• [Journal Article] Oxytocin : a thetapeutic target for lental disorders (2012)
  • Author(s): Mitsuhiro Matsuzaki, Hiroaki Matsushita. Kazuhito Tomizawa, Hideki Matsui
  • Journal Title: J Physiol Sci Volume: 62 Pages: 119-133
  • Peer Reviewed
• [Presentation] The development of whitening peptide with peptide percutaneous drug delivery system (2015)
  • Author(s): 道上宏之 大久保奈々子 北松瑞生 松下博昭 西木禎一 松井秀樹
  • Organizer: 第92回 日本生理学会大会
  • Place of Presentation: 神戸国際会議場・展示場 （神戸 ポートアイランド）
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] 脳血液関門通過可能なアクチン重合抑制薬による膠芽腫に対する抗浸潤効果の検討 (2014)
  • Author(s): 道上宏之 林桂一郎 山田浩司 中山大輝 黒住和彦 市川智継 松下博昭 西木禎一 竹居孝二 富澤一仁 松井秀樹
  • Organizer: 第３２回日本脳腫瘍学会学術大会
  • Place of Presentation: シェラトン・グランデ・トーキョー・ベイ・ホテル「
  • Year and Date: 2014-11-30 – 2014-12-02
• [Presentation] 臨床応用へ向けた新規BSH-peptideの開発およびその薬物動態評価 (2014)
  • Author(s): 林 祐里、道上宏之、井口佳哉、北松瑞生、竹中文章、松下博昭、西木禎一、松井秀樹
  • Organizer: 平成26年度京都大学原子炉実験所専門研究会
  • Place of Presentation: 京都大学原子炉実験所 事務棟大会議室
  • Year and Date: 2014-09-29 – 2014-09-30
• [Presentation] Short-Arginine domainを用いた新規BSH-peptideによる臨床応用へ向けた取り組み (2014)
  • Author(s): 林祐里,道上宏之, 井口佳哉,北松瑞生,松下博昭,西木禎一,富澤一仁,松井秀樹
  • Organizer: 第11回日本中性子捕捉療法学会学術大会
  • Place of Presentation: 大阪大学（吹田キャンパス）コンベンションセンター
  • Year and Date: 2014-07-05 – 2014-07-06
• [Presentation] Novel multi-linked mercaptoundecahydrododecaborate (BSH) fused cell-penetrating peptide accelerated boron neutron capture therapy (BNCT) (2014)
  • Author(s): Michiue H, Iguchi Y, Sakurai Y, Kondo N, Kitamatsu M, Kawabata S, Miyatake, Nishiki T, Tomizawa K, Ono K, Matsui H
  • Organizer: 16th International Congress on Neutron Capture Therapy
  • Place of Presentation: Pörssitalo, Fabianinkatu 14, 00100 Helsinki, Finland
  • Year and Date: 2014-06-14 – 2014-06-19
• [Presentation] オキシトシンは情動と記憶の制御を行い、精神疾患治療の標的である(口演)。 (2012)
  • Author(s): 松井秀樹
  • Organizer: 第90回日本生理学会大会(シンポジウム『母と子の相互関係は脳を変容する』)
  • Place of Presentation: タワーホール船堀(東京)
  • Year and Date: 2012-03-27
• [Presentation] タンパク質セラピー法と標的型バイオナノカプセルによる中性子補足療法剤の開発 。 (2012)
  • Author(s): 松井秀樹
  • Organizer: 第29回 医用高分子研究会講座
  • Place of Presentation: 産業技術総合研究所 臨海副都心センター(東京)(招待講演)
• [Presentation] 低酸素誘導による膠芽腫新規浸潤因子の発見と機能解析 (2012)
  • Author(s): 道上宏之、松井秀樹, 他
  • Organizer: 第30回日本脳腫瘍学会学術集会
  • Place of Presentation: グランドプリンスホテル広島(広島市)
• [Presentation] 小胞放出Ca2+センサーシナプトタグミンの中間型SNARE膜融合複合体への結合と解離(口演) (2012)
  • Author(s): 増本年男、松井秀樹, 他
  • Organizer: 第64回日本生理学会中国四国地方会
  • Place of Presentation: 高知市文化プラザ(高知市)
• [Presentation] Requirement of Ca2+ binding to the C2B for dissociation of synaptotagmin from trans-SNARE complexes (poster) (2012)
  • Author(s): Masumoto T, Matsui H, et al
  • Organizer: Neuroscience 2012 (42nd annual meeting of the Society for Neurosience)
  • Place of Presentation: Ernest N. Morial Convention Center (New Orleans, LA. USA)
• [Presentation] Ca2+-independent binding of synaptotagrain to syntaxin via its C2B effectorregion (poster) (2012)
  • Author(s): Nishiki T, Matsui H, et al
  • Organizer: Neuroscience 2012 (42nd annual meeting of the Society for Neurosience)
  • Place of Presentation: Ernest N. Morial Convention Center (New Orleans, LA, USA)
• [Presentation] SCN9A遺伝子変異/多型がドラベ症候群の臨床型に及ぼす影響 (2012)
  • Author(s): 大守伊織、松井秀樹, 他
  • Organizer: 第46回日本てんかん学会
  • Place of Presentation: 都市センターホテル(東京)
• [Presentation] Ca2+-induced dissociation of synaptotagiin from trans-SNARE complexes (poster) (2012)
  • Author(s): T Masumoto, H Matsui, et al
  • Organizer: Neuroscience 2012 (第35回日本神経科学大会)
  • Place of Presentation: 名古屋国際会議場
• [Remarks]
  • URL: http://seiril.med.okayama-u.ac.jp/