Anti-tumor effect of alkylating pyrrole-imidazole polyamide targeting rhabdomyosarcoma specific fusion gene PAX3-FOXO1
| Project/Area Number |
15K10930
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatric surgery
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| Research Institution | Nihon University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
杉藤 公信 日本大学, 医学部, 研究医員 (10328750)
藤原 恭子 日本大学, 医学部, 助教 (40595708)
越永 從道 日本大学, 医学部, 教授 (70205376)
植草 省太 日本大学, 医学部, 専修医 (70746338)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 医学 / 臨床外科学 / 小児腫瘍学 / 横紋筋肉腫 / ピロール・イミダゾール・ポリアミド / CBI / 融合遺伝子 |
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| Outline of Final Research Achievements |
Alveolar rhabdomyosarcoma (ARMS) is one of the typical subtypes of rhabdomyosarcoma (RMS), and is characterized by a frequent chromosomal translocation. This translocation results in the formation of fusion gene including PAX3-FOXO1, which possess tumor promoting functions. In the present study, we have synthesized pyrrole-imidazole polyamides (PIP) recognizing PAX3-FOXO1 fusion site and conjugated them with alkylating agent chlorambucil. That molecule (Rhab-ChB1) could specifically bind to DNA with PAX3-FOXO1 fusion site sequence, but not to negative control DNA. Rhab-ChB1 showed strong growth suppressing effect, not only on fusion gene positive cells, but also on fusion gene negative cells. Flow cytometry analysis elucidated that the treatment with Rhab-ChB 1 provoked G2/M arrest. Since the effective concentration of Rhab-ChB1 was almost 100 times lower than that of ChB itself, Rhab-ChB1 may be developed as a new effective alkylating agent.
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Report
(4 results)
Research Products
(2 results)
