| Autor: |
Jessica E. Sagers, Adam S. Brown, Sasa Vasilijic, Rebecca M. Lewis, Mehmet I. Sahin, Lukas D. Landegger, Roy H. Perlis, Isaac S. Kohane, D. Bradley Welling, Chirag J. Patel, Konstantina M. Stankovic |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
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| Zdroj: |
Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
2045-2322 |
| DOI: |
10.1038/s41598-018-23609-7 |
| Popis: |
Abstract The computational repositioning of existing drugs represents an appealing avenue for identifying effective compounds to treat diseases with no FDA-approved pharmacotherapies. Here we present the largest meta-analysis to date of differential gene expression in human vestibular schwannoma (VS), a debilitating intracranial tumor, and use these data to inform the first application of algorithm-based drug repositioning for this tumor class. We apply an open-source computational drug repositioning platform to gene expression data from 80 patient tumors and identify eight promising FDA-approved drugs with potential for repurposing in VS. Of these eight, mifepristone, a progesterone and glucocorticoid receptor antagonist, consistently and adversely affects the morphology, metabolic activity, and proliferation of primary human VS cells and HEI-193 human schwannoma cells. Mifepristone treatment reduces VS cell viability more significantly than cells derived from patient meningiomas, while healthy human Schwann cells remain unaffected. Our data recommend a Phase II clinical trial of mifepristone in VS. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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