RESUMEN
We report on the underlying molecular mechanisms likely responsible for the high-level fluconazole resistance in a Candida lusitaniae clinical isolate. Fluconazole resistance correlated with overexpression of ERG11 and of several efflux pump genes, in particular, the orthologs of the Candida albicans MDR1, PDR16, CDR1, CDR2, and YOR1.
Asunto(s)
Candida/efectos de los fármacos , Candida/genética , Farmacorresistencia Fúngica/genética , Fluconazol/farmacología , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Transportadoras de Casetes de Unión a ATP/genética , Sistema Enzimático del Citocromo P-450/genética , Cartilla de ADN , Proteínas Fúngicas/genética , Humanos , Proteínas de Transporte de Membrana/genética , Metiltransferasas/genética , Oxidorreductasas/genética , Reacción en Cadena de la Polimerasa/métodosRESUMEN
Circadian rhythms can be altered in severe illness such as cancer; the rest-activity circadian cycle has been used as a reference for the administration of chemotherapy at specific times in order to improve tolerability and efficacy. We assessed the feasibility of the method in our center in a sample of patients with metastatic colorectal cancer selected for chronomodulated chemotherapy. Activity of the circadian rhythms were measured non-invasively in 10 patients with metastatic colorectal cancer by wrist actimetry, and compared to healthy subjects. Patients and healthy subjects were requested to wear an actigraph, a wristwatch that records the number of accelerations per minute, for 3 days. Healthy subjects exhibited high activity levels during daytime, followed by low activity levels during the night. In patients, the contrast between daytime activity and nocturnal sleep was noticeably less marked, and a wide inter-patient variability was observed. All the patients wore the actigraph with a total compliance. Actimetry may provide a simple and innovative tool to study the circadian system and may be considered as an objective and accurate method to evaluate the individual health status ("conditions of life") in cancer patients, independently of all ("quality of life" questionnaires.