| Project/Area Number |
17K16812
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Urology
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| Research Institution | Keio University |
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Principal Investigator |
Ogihara Koichiro 慶應義塾大学, 医学部(信濃町), 特任助教 (30626677)
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| Research Collaborator |
KIKUCHI Eiji
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 膀胱癌 / 癌幹細胞 / CD44 / sulfasalazine / シスプラチン / 膀胱内注入療法 / 癌 / 細胞・組織 / 発現制御 / トランスレーショナルリサーチ / 薬剤反応性 |
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| Outline of Final Research Achievements |
CD44v protein expression was examined immunohistochemically in muscle invasive bladder cancer (MIBC) patients who underwent radical cystectomy. CD44v expression was independently associated with disease recurrence and cancer-specific death in MIBC. Sulfasalazine (SSZ) exerted cytotoxic effects against bladder cancer cells. SSZ in combination with cisplatin (CDDP) appeared to exert strong cytotoxic effects. The inhibitory effects of SSZ with or without CDDP were investigated using murine lung metastatic models. The combination of SSZ with CDDP exerted stronger inhibitory effects on the establishment of lung tumor nodules than SSZ or CDDP alone. The inhibitory effects of SSZ was also investigated using murine orthotopic models. Bladder weight in mice treated with SSZ was significantly lower than that in mice treated with vehicle control.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究において癌幹細胞マーカーであるCD44vの発現が膀胱癌の独立した予後因子であることを示し、そのCD44vに関連した治療抵抗性膀胱癌に対する新規治療としてsulfasalazineを用いた治療の確立が可能であることが示唆された。
癌幹細胞は膀胱癌だけでなく、消化器癌をはじめとする多くの癌に存在している。本研究の成果は癌研究に及ぼす波及効果はもちろんのこと、他疾患における新規治療の新たな切り口となり得るため、その波及効果は非常に大きいと推測される。
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