Development of novel combined therapies with anti-EGFR monoclonal antibody and anticancer drug for malignant gliomas
| Project/Area Number |
22591618
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Kyorin University |
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Principal Investigator |
NAGANE Motoo 杏林大学, 医学部, 教授 (60327468)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 神経膠腫 / EGFR / モノクローナル抗体 / 分子標的治療薬 / 化学療法 / EGFRvIII / シグナル伝達阻害 / MMR / EGVFvIII / Akt |
|---|
| Research Abstract |
Treatment of glioblastoma (GBM) cells overexpressing driver oncogenic wild-type EGFR or a mutant EGFRvIII with a humanized anti-EGFR monoclonal antibody nimotuzumab (Nimo) resulted in reduction in tyrosine phosphorylation of EGFRvIIIpreferentially, which was associated with a decrease in Akt phosphorylation. Combination treatment of nimotuzumab with temozolomide (TMZ), the standard chemotherapeutic drug for GBM, significantly suppressed growth and elongated survival of mice bearing subcutaneous or intracerebral human GBM tumors overexpressing EGFRvIII. The sensitivity to the combination treatment was affected in regrown tumor cells which had lost expression of mismatch repair (MMR) proteins MSH6 and MLH1, suggesting that the resistance to this combination treatment might involve expression changes of MMR effectors.
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Report
(4 results)
Research Products
(78 results)
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[Journal Article] SHP-2/PTPN11 mediates gliomagenesis driven by PDGFRA and Ink4a/Arf aberrations in mice and humans2011
Author(s)
Liu K-W, Feng H, Bachoo R, Kazlauskas A, Smith EM, Symes K, Hamilton RL, Nagane M, Nishikawa R, Hu B, Cheng S-Y
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Journal Title
J Clin Invest
Volume: 121
Pages: 905-917
Related Report
Peer Reviewed
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[Journal Article] SHP-2/PTPN11 mediates gliomagenesis driven by PDGFRA and Ink4a/Arf aberrations in mice and humans.2011
Author(s)
Liu K-W, Feng H, Bachoo R, Kazlauskas A, Smith EM, Symes K, Hamilton RL, Nagane M, Nishikawa R, Hu B, Cheng S-Y
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Journal Title
J Clin Invest
Volume: (In press)
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Peer Reviewed
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[Presentation] 再発悪性神経膠腫を対象としたベバシズマブの多施設共同第II相臨床試験2011
Author(s)
永根基雄, 西川亮, 成田善孝, 倉津純一, 小林浩之, 杉山一彦, 青木友和, 篠浦伸禎, 高野晋吾, 岡田和喜, 松谷雅生
Organizer
第49回日本癌治療学会
Place of Presentation
名古屋
Year and Date
2011-10-29
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