Basic research of DDS therapy for malignant brain tumor

• Project/Area Number: 25462274
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kumamoto University
• Principal Investigator: Kuroda Junichiro 熊本大学, 大学院生命科学研究部(医), 助教 (90536731)
• Co-Investigator(Kenkyū-buntansha): 倉津 純一 熊本大学, 大学院生命科学研究部(医), 教授 (20145296) ; 中村 英夫 熊本大学, 医学部附属病院, 講師 (30359963) ; 秀 拓一郎 熊本大学, 医学部附属病院, 診療講師 (40421820) ; 篠島 直樹 熊本大学, 医学部附属病院, 寄附講座教員 (50648269) ; 矢野 茂敏 熊本大学, 大学院生命科学研究部(医), 准教授 (60332871) ; 牧野 敬史 熊本大学, 医学部附属病院, 講師 (90381011)
• Research Collaborator: MATSUMURA Yasuhiro
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: brain tumor / drug delivery system / tissue factor / antibody / ADC / drug delivery / DDS / 血管透過性 / 悪性グリオーマ / モノクローナル抗体 / ドラッグデリバリーシステム / がんと凝固 / fibrin / monoclonal antibody

Outline of Final Research Achievements

We focused on brain tumor cell factor and tumor tissue environmental factor to develop DDS therapy for malignant brain tumor.Tissue factor is one of the trigger molecule for exogenous coagulation in malignant tumor. We examined drug delivery method using anti tissue factor factor monoclonal antibody. First of all, immunostaining of glioma was carried out, and it was confirmed that tissue factor was highly expressed as malignancy increased. Next, we conducted animal experiments in which the glioblastoma cell line was transplanted subcutaneously, and it was confirmed that the anti-tissue factor antibody highly accumulated in the tumor and did not accumulate in normal organs. It is expected to develop into an antibody drug complex using tissue factor antibody.

Research Products

• [Journal Article] A case of an epithelioid glioblastoma with the BRAF V600E mutation colocalized with BRAF intact low-grade diffuse astrocytoma. (2016)
  • Author(s): Kuroda JI, Nobusawa S, Nakamura H, Yokoo H, Ueda R, Makino K, Yano S, Kuratsu JI.
  • Journal Title: Neuropathology Volume: 36 Issue: 2 Pages: 181-186
  • DOI: 10.1111/neup.12258
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Discovery of an uncovered region in fibrin clots and its clinical significance. (2013)
  • Author(s): Hisada Y, Yasunaga M, Hanaoka S, Saijou S, Sugino T, Tsuji A, Saga T, Tsumoto K, Manabe S, Kuroda J, Kuratsu J, Matsumura Y.
  • Journal Title: Sci Rep. Volume: 3 Issue: 1 Pages: 2604-2604
  • DOI: 10.1038/srep02604
  • Peer Reviewed
• [Presentation] 抗組織因子抗体を用いたSPECTによるグリオーマイメージング (2016)
  • Author(s): 高島大輝、安永正浩、黒田順一郎、松村保広 他
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-10-06
• [Presentation] The development of novel imaging and treatment that focuses on coagulation dysfunction of malignant gliomas (2015)
  • Author(s): J. Kuroda , H. Takashima , M. Yasunaga , Y. Matsumura , J. Kuratsu
  • Organizer: EANS2015
  • Place of Presentation: Spain, Madrid
  • Year and Date: 2015-10-18
  • Int'l Joint Research
• [Presentation] 悪性グリオーマの凝固機能異常に着目した新規イメージング及び治療法の開発 (2015)
  • Author(s): 黒田順一郎、高島大輝、安永正浩、松村保広、倉津純一
  • Organizer: 第74回日本脳神経外科学術総会
  • Place of Presentation: 北海道、札幌
  • Year and Date: 2015-10-14