Molecular targeted therapy focusing invasion signaling in malignant glioma cell
Project/Area Number |
23592117
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Cerebral neurosurgery
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Research Institution | Kanazawa University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
MINAMOTO Toshinari 金沢大学, がん研究所, 教授 (50239323)
SATO Hiroshi 金沢大学, がん研究所, 教授 (00115239)
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Project Period (FY) |
2011 – 2013
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Project Status |
Completed (Fiscal Year 2013)
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Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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Keywords | グリオーマ / 分子標的療法 / Akt / Notch / 増殖 / 浸潤 / GSK3β / テモゾロミド / 薬剤感受性 / MGMT / 膠芽腫 / シグナル伝達 |
Research Abstract |
We assessed the therapeutic possibility of inhibiting Notch and Akt in gliomas using the clinically available, selective small molecule inhibitors. Additionally, we investigated the molecular mechanisms of sensitization of glioblastoma (GBM) cells to temozolomide (TMZ) by GSK3beta inhibition. Notch and Akt inhibitors significantly inhibited cell growth, migration, and invasion in a dose-dependent manner. However, the effect of combination treatment did not exceed that of Akt inhibitor monotherapy in proliferation assay. Inhibition of invasion, further enhanced by combination therapy. Therefore, combination therapy may be effective for inhibiting invasion but not proliferation. GSK3beta inhibition enhanced TMZ effect. c-Myc binds to the MGMT promoter with consequent recruitment of DNMT3A, regulating the levels of MGMT promoter methylation. Therefore, GSK3beta inhibition enhances TMZ effect by silencing MGMT expression via c-Myc-mediated promoter methylation.
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Report
(4 results)
Research Products
(87 results)
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[Journal Article] PCDH10 is required for the tumorigenicity of glioblastoma cells2014
Author(s)
Kanae Echizen, Mitsutoshi Nakada , Tomoatsu Hayashi, Hemragul Sabit, Takuya Furuta, Miyuki Nakai, Ryo Koyama-Nasu, Yukiko Nishimura, Kenzui Taniue, Yasuyuki Morishita, Shinji Hirano, Kenta Terai, Tomoki Todo, Yasushi Ino, Akitake Mukasa, Shunsaku Takayanagi, Ryohei Ohtani, Nobuhito Saito, Tetsu Akiyama
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Journal Title
Biochem. Biophys. Res. Commun.
Volume: 444
Issue: 1
Pages: 13-18
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Ligand-dependent EphB1 signaling suppresses glioma invasion and correlates with patient survival2013
Author(s)
Teng L, Nakada M, Furuyama N, Sabit H, Furuta T, Hayashi Y, Takino T, Dong Y, Sato H, Sai Y, Miyamoto KI, Berens ME, Zhao SG, Hamada JI
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Journal Title
Neuro-Oncology
Volume: 15
Issue: 12
Pages: 1710-1720
DOI
Related Report
Peer Reviewed
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[Journal Article] Integrin α3 is overexpressed in glioma stem-like cells and promotes invasion.2013
Author(s)
Nakada M, Nambu E, Furuyama N, Yoshida Y, Takino T, Hayashi Y, Sato H, Sai Y, Tsuji T, Miyamoto KI, Hirao A, Hamada JI.
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Journal Title
Br J Cancer
Volume: 108
Pages: 2516-2524
DOI
ISBN
9789400747180, 9789400747197
Related Report
Peer Reviewed
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[Journal Article] Combination therapy using Notch and Akt inhibitors is effective for suppressing invasion but not proliferation in glioma cells2012
Author(s)
Jin R, Nakada M, Teng L, Furuta T, Sabit H, Hayashi Y, Demuth T, Hirao A, Sato H, Zhao G, Hamada JI
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Journal Title
Neuroscience letters
Volume: 534
Pages: 316-321
DOI
Related Report
Peer Reviewed
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[Journal Article] Recurrent anaplastic meningioma treatedby sunitinib based on results fromquantitative proteomics2011
Author(s)
Yoshikawa, A., Nakada, M., Ohtsuki, S., Hayashi, Y., Obuchi, W., Sato, Y., Ikeda, C., Watanabe, T., Kawahara, Y., Hasegawa, T., Sabit, H., Kita, D., Nakanuma, Y., Terasaki, T. and Hamada, J.
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Journal Title
NeuropatholAppl Neurobiol
Volume: 38
Issue: 1
Pages: 105-10
DOI
Related Report
Peer Reviewed
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[Journal Article] Aberrant SignalingPathways in Glioma2011
Author(s)
Nakada, M., Kita, D., Watanabe, T., Hayashi, Y., Teng, L., Pyko, I. V. andHamada, J.
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Journal Title
Cancers
Volume: 3
Issue: 3
Pages: 3242-78
DOI
Related Report
Peer Reviewed
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[Presentation] Glycogen synthase kinase 3βpromotes glioma invasion via the FAK/Rac1/JNK/MMP2 pathway2013
Author(s)
Nakada M, Furuta T, Sabit H, Chikano Y, Hayashi Y, Sato H, Minamoto T, Hamada JI
Organizer
4^<rd> Quadrennial Meeting of the World Federation of Neuro-Oncology
Place of Presentation
Marriott Marquis Hotel, San Francisco, CA, USA
Related Report
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[Presentation] Glycogen synthase kinase 3β promotes glioma invasion via the FAK/Rac1/JNK/MMP2 pathway.2013
Author(s)
Nakada M, Furuta T, Sabit H, Chikano Y, Hayashi Y, Sato H, Minamoto T, Hamada JI.
Organizer
4rd Quadrennial Meeting of the World Federation of Neuro-Oncology
Place of Presentation
Marriott Marquis Hotel, San Francisco, CA, USA
Related Report
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[Presentation] Phase I/II study for recurrent glioblastoma with the drugs inhibiting GSK3β2012
Author(s)
Nakada M, Hayashi Y, Miyashita K, Kinoshita M, Furuta T, Sabit H, kita D, Hayashi Y, Uchiyama N, Kawakami K, Minamoto T, Hamada JI
Organizer
Society for Neuro-Onology 17th Annual Meeting 2011
Place of Presentation
Hilton Hotel, Washington DC, USA
Related Report
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[Presentation] 絶対定量プロテオミクスを使用した膠芽腫のプロファイリングとテーラーメイド分子標的療法の提唱2012
Author(s)
中田光俊、林裕,小渕航,大槻純男,古田拓也,木下雅史,渡邉卓也,田中慎吾,喜多大輔,宮下勝吉,淑瑠ヘムラサビット,毛利正直,林康彦,内山尚之,寺崎哲也,濵田潤一郎
Organizer
第71回日本脳神経外科学会総会
Place of Presentation
大阪国際会議場(大阪)
Related Report
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[Presentation] Molecular target profiling by absolute quantitative proteomics in glioblastoma2012
Author(s)
Nakada M, Niska JR, Nambu E, Furuyama N, Hayashi Y, Kita D, Hayashi Y, Berens ME, Hamada JI
Organizer
The 19^<th> International Conference on Brain Tumor Research & Therapy
Place of Presentation
Marriott Gateway on the Falls, Niagara Falls, Canada
Related Report
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[Presentation] Aberrant glycogen synthase kinase 3βis involved in glioma invasion2012
Author(s)
Nakada M, Chikano Y, Sabit H, Furuta T, Miyashita K, Hayashi Y, Sato H, Kawakami K, Minamoto T, Hamada JI
Organizer
9^<th >Meeting for the Asian Society for Neuro-Oncology
Place of Presentation
Taipei International Convention Center, Taiwan
Related Report
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[Presentation] Molecular target profiling by absolute quantitative proteomics in glioblastoma2012
Author(s)
Nakada M, Niska JR, Nambu E, Furuyama N, Hayashi Y, Kita D, Hayashi Y, Berens ME, Hamada JI
Organizer
The 19th International Conference on Brain Tumor Research & Therapy
Place of Presentation
Marriott Gateway on the Falls, Niagara Falls, Canada
Related Report
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[Presentation] Aberrant glycogen synthase kinase 3β is involved in glioma invasion2012
Author(s)
Nakada M, Chikano Y, Sabit H, Furuta T, Miyashita K, Hayashi Y, Sato H, Kawakami K, Minamoto T, Hamada JI
Organizer
9th Meeting for the Asian Society for Neuro-Oncology
Place of Presentation
Taipei International Convention Center, Taiwan
Related Report
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