2017 Fiscal Year Final Research Report
Assessment of the efficacy of combined treatment with temsirolimus and custirsen for renal cell carcinoma
| Project/Area Number |
15K10589
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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 |
Urology
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 腎細胞癌 / temsirolimus / custirsen / clusterin |
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| Outline of Final Research Achievements |
We investigated the efficacy of combined treatment with temsirolimus plus custirsen in a human RCC Caki-1 model. Although clusterin expression was increased by temsirolims, additional treatment of Caki-1 significantly inhibited clusterin upregulation. Combined treatment of temsirolimus and custirsen synergistically enhanced the sensitivity of Caki-1 to temsirolimus. Apoptotic changes were marked in Caki-1 following combined treatment with a sublethal dose of temsirolimus and custirsen, accompanying the significant downregulation of Mcl-1. In-vivo systemic administration of temsirolimus plus custirsen significantly inhibited the growth of Caki-1 tumors compared with that of temsirolimus plus control ODN.
Silencing of clusterin using custirsen resulted in the further enhancement of proapoptotic activity induced by temsirolimus in a human RCC model.
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| Free Research Field |
泌尿器科悪性腫瘍
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