Pathogenesis of multi-step progression of urothelial carcinoma and development of innovative treatment
| Project/Area Number |
19K18612
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | The University of Tokushima |
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Principal Investigator |
DAIZUMOTO Kei 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (10745516)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 尿路上皮癌 / DDX31 / TP53 / p53 / 多段階進展 / EGFR / BBN / 膀胱癌 |
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| Outline of Research at the Start |
転移性尿路上皮癌の予後は非常に悪く、全身化学療法の有効性は低く重篤な副作用のため継続が困難となることが多い。治療効果が高く副作用の少ない治療法転移性尿路上皮癌の治療法開発のため、Cancer-specific-therapy を目的とし癌特異的発現分子として新規核小体制御分子Dead box polypeptide 31 (DDX31)を同定した。DDX31は尿路上皮癌の多段階進展機構の初期段階から進行段階で重要な機能を持っていることがわかった。これらの結果をもとに本研究では尿路上皮癌の多段階進展機構の病態解明とDDX31を標的とした治療開発を行う。
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| Outline of Final Research Achievements |
The anti-tumor effect of DDX31 was verified in a preclinical model, and the amino acid sequence of the reciprocal site of DDX31 was identified to create a dominant negative peptide. We also examined the relationship between p53 and DDX31 in the uroepithelial carcinogenesis model using N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) as a uroepithelial carcinogenesis model. The results showed that DDX31 RNA expression was upregulated in the bladder tissue over time compared to the control group.
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| Academic Significance and Societal Importance of the Research Achievements |
尿路上皮癌の遺伝子変異で大きく病態として分かれるのはTP53変異である。これまでの研究から尿路上皮癌・初期段階のTP53 wild type、中期段階のTP53 muation、後期段階のEGFRやHER2などReceptor of Tyrosine kinase (RTK)の活性化の病態解明にはまだ未解明な部分が多く、詳細に解析することで治療法の開発につながることが期待される。最終的に、尿路上皮癌の多段階進展機能のさらなる新機能発見と新規治療法の開発につながっていくことが期待される。
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Report
(3 results)
Research Products
(26 results)
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[Presentation] Galectin-3 is involved in the tumor progression and drug resistance induced by taxane chemotherapy and poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor in castration-resistant prostate cancer2019
Author(s)
Tomoharu Fukumori,Kei Daizumoto, Megumi Tsuda, Keisuke Ozaki, Yoshito Kusuhara, Hidehisa Mori, Tomoya Fukawa, Yasuyo Yamamoto, Kunihisa Yamaguchi, Masayuki Takahashi, Hiro-omi Kanayama,
Organizer
AUA
Related Report
Int'l Joint Research
