Drag repositioning for malignant glioma targeting glioma stem cells
Project/Area Number |
26293322
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Neurosurgery
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Research Institution | Kanazawa University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
HIRAO Atsushi 金沢大学, がん進展制御研究所, 教授 (90343350)
MINAMOTO Toshinari 金沢大学, がん進展制御研究所, 教授 (50239323)
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Research Collaborator |
DONG Yu
FURUTA Takuya
SABIT Hemragul
KITABAYASHI Tomohiro
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
|
Keywords | グリオーマ / 幹細胞 / ドラッグリポジショニング / 脳神経疾患 / 化学療法 |
Outline of Final Research Achievements |
Glioma stem cell (GSC)-targeted therapy is a promising approach to treat patients with glioblastoma (GBM). Here, we identified fluspirilene, a traditional antipsychotic drug, as a GSC-targeting agent, selected from thousands of existing drugs with the purpose of drug repositioning. We initially screened drug libraries for small-molecule compounds showing a greater efficacy in inhibiting the proliferation and survival of different GSC lines. Drugs already reported to show therapeutic effects against GBM or those under clinical trials were excluded from subsequent screening. Among the candidate drugs, fluspirilene demonstrated a significant inhibitory effect on the proliferation and invasion of glioma cells as well as in the model mice treated with the drug. These effects were associated with the inactivation of the signal transducer and activator of transcription 3 (STAT3). Redeveloping of fluspirilene is a promising approach for the treatment of GBM.
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] The role of AKT isoforms in glioblastoma: AKT3 delays tumor progression2016
Author(s)
Joy A, Kapoor M, Georges J, Butler L, Chang Y, Li C, Crouch A, Smirnov I, Nakada M, Hepler J, Marty M, Feuerstein BG
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Journal Title
J Neurooncol
Volume: 130
Pages: 43-52
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Serine/Threonine kinase MLK4 determines Mesenchymal Identity in Glioma Stem Cells in an NFkB-dependent manner2016
Author(s)
Kim SH, Ezhilarasan R, Chhipa R, Ladner K, Phillips E, Sparks A, Taylor D, Furuta T, Sabit H, Kurozumi K, Kuroiwa T, Akio A, Gallego-Perez1 D, Sulman EP, Cheng S, Lee J, Nakada M, Guttridge D, DasGupta B, Goidts V, Bhat KP, Walker J, Nakano I.
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Journal Title
Cancer Cell
Volume: 29
Issue: 2
Pages: 201-213
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Recurrent neomorphic mutations of MTOR in central nervous system and testicular germ cell tumors may be targeted for therapy2016
Author(s)
Ichimura K, Fukushima S, Totoki Y, Matsushita Y, Otsuka A, Tomiyama A, Niwa T, Takami H, Nakamura T, Suzuki T, Fukuoka K, Yanagisawa T, Mishima K, Nakazato Y, Hosoda F, Narita Y, Shibui S, Yoshida A, Mukasa A, Saito N, Kumabe T, Kanamori M, Tominaga T, Kobayashi K, Shimizu S, Nagane M, Iuchi T, Nakada M, et al.
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Journal Title
Acta Neuropathologica
Volume: ND
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Strong therapeutic potential of γ-secretase inhibitor MRK003 for CD44-high and CD133-low glioblastoma initiating cells.2015
Author(s)
Tanaka S, Nakada M, Yamada D, Nakano I, Todo T, Ino Y, Hoshii T, Tadokoro Y, Ohta K, Ali MA, Hayashi Y, Hamada J, Hirao A.
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Journal Title
J Neurooncol.
Volume: 121
Issue: 2
Pages: 239-50
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Glycogen synthase kinase 3β sustains invasion of glioblastoma via the focal adhesion kinase, Rac1 and c-Jun N-terminal kinase-mediated pathway.2015
Author(s)
Chikano Y, Domoto T, Furuta T, Sabit H, Kitano-Tamura A, Ilya V. Pyko, Takino T, Sai Y, Hayashi Y, Sato H, Miyamoto K, Nakada M, MinamotoT.
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Journal Title
Molecular Cancer Therapeutics
Volume: 14
Issue: 2
Pages: 564-574
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Drug repositioning targeting glioma stem cells2016
Author(s)
Nakada M, Dong Y, Kitabayashi Y, Sabit H, Furuta T, Hirao A
Organizer
Society for Neuro-Onology 21st Annual Meeting 2016
Place of Presentation
Scottsdale Fairmont Princess Hotel, Scottsdale, Arizona, USA
Year and Date
2016-11-17
Related Report
Int'l Joint Research
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