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PLoS One ; 5(4): e9948, 2010 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-20376347

RESUMEN

BACKGROUND: Xenotropic murine leukemia-related retrovirus (XMRV) is a recently discovered retrovirus that has been linked to human prostate cancer and chronic fatigue syndrome (CFS). Both diseases affect a large fraction of the world population, with prostate cancer affecting one in six men, and CFS affecting an estimated 0.4 to 1% of the population. PRINCIPAL FINDINGS: Forty-five compounds, including twenty-eight drugs approved for use in humans, were evaluated against XMRV replication in vitro. We found that the retroviral integrase inhibitor, raltegravir, was potent and selective against XMRV at submicromolar concentrations, in MCF-7 and LNCaP cells, a breast cancer and prostate cancer cell line, respectively. Another integrase inhibitor, L-000870812, and two nucleoside reverse transcriptase inhibitors, zidovudine (ZDV), and tenofovir disoproxil fumarate (TDF) also inhibited XMRV replication. When combined, these drugs displayed mostly synergistic effects against this virus, suggesting that combination therapy may delay or prevent the selection of resistant viruses. CONCLUSIONS: If XMRV proves to be a causal factor in prostate cancer or CFS, these discoveries may allow for rational design of clinical trials.


Asunto(s)
Evaluación Preclínica de Medicamentos/métodos , Síndrome de Fatiga Crónica/virología , Gammaretrovirus/efectos de los fármacos , Neoplasias de la Próstata/virología , Pirrolidinonas/farmacología , Infecciones por Retroviridae/tratamiento farmacológico , Infecciones Tumorales por Virus/tratamiento farmacológico , Antivirales , Línea Celular Tumoral , Femenino , Humanos , Virus de la Leucemia Murina/efectos de los fármacos , Masculino , Pruebas de Sensibilidad Microbiana , Pirrolidinonas/uso terapéutico , Raltegravir Potásico , Replicación Viral/efectos de los fármacos
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