| Project/Area Number |
22591036
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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 |
Hematology
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| Research Institution | Osaka University |
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Principal Investigator |
MIZUKI Masao 大阪大学, 医学部附属病院, 准教授 (80283761)
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| Co-Investigator(Kenkyū-buntansha) |
KANAKURA Yuzuru 大阪大学, 医学系研究科, 教授 (20177489)
SHIBAYAMA Hirohiko 大阪大学, 医学系研究科, 講師 (60346202)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 血液腫瘍学 / レセプター型チロシンキナーゼ / プロテアゾーム阻害剤 / 活性化変異 / ER stress / 樹状細胞 / 白血病 / plasmacytoid DC / class I mutation / class II mutation / FGFR3 / multiple myeloma |
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| Research Abstract |
The ectopically expressed fibroblast growth factor receptor 3 (FGFR3) and its constitutive active mutations have been detected in patients with multiple myeloma (MM). This study investigated whether the cytotoxic effects of bortezomib on malignant plasma cells are associated with FGFR3 expression andthe existence of mutations of FGFR3. Materials and Methods: Cell apoptosis assays were performed in a plasmacytoma cell line, FR4 cells and a myeloma cell line, RPMI8226 cells overexpressing wild-type FGFR3 (FGFR3WT) or two different mutants, FGFR3K650E or FGFR3Y373C, and the induction of endoplasmic reticulum (ER) stress protein was compared between each type of cells. Results: FR4 cells with FGFR3K650E showed enhanced sensitivity to bortezomib together with increased induction of ER stress proteins, compared to FR4 cells with mock, FGFR3WT or FGFR3Y373C. RPMI8226 cells with FGFR3K650E also showed enhanced bortezomib sensitivity. Conclusion: This study indicated that FGFR3K650E is associated with bortezomib sensitivity in malignant plasma cells via ER stress pathways.
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