RESUMO
Pyrosequencing was compared to Sanger dideoxy sequencing to detect mutations in FKS1 responsible for reduced echinocandin susceptibility in Candida albicans. These methods were in complete agreement for 10 of 12 clinical isolates with elevated echinocandin MICs, supporting the potential feasibility of pyrosequencing to detect mutations within diploid fungi.
Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/genética , Análise Mutacional de DNA/métodos , Equinocandinas/farmacologia , Genes Fúngicos , Glucosiltransferases/genética , Mutação Puntual , Anidulafungina , Sequência de Bases , Candida albicans/enzimologia , Candida albicans/isolamento & purificação , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Caspofungina , DNA Fúngico/genética , Farmacorresistência Fúngica/genética , Humanos , Lipopeptídeos/farmacologia , MicafunginaRESUMO
Incomplete killing was observed for caspofungin against Candida glabrata, which was associated with increased SLT2 expression and elevated chitin content. In contrast, fungicidal activity and no chitin increase were observed in an isogenic Delta slt2 strain, suggesting a role for SLT2 and chitin production in the response of C. glabrata to caspofungin.
Assuntos
Antifúngicos/farmacologia , Candida glabrata/efeitos dos fármacos , Quitina/metabolismo , Farmacorresistência Fúngica , Equinocandinas/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Candida glabrata/enzimologia , Candida glabrata/metabolismo , Caspofungina , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Lipopeptídeos , Testes de Sensibilidade Microbiana , Proteínas Quinases Ativadas por Mitógeno/genética , Regulação para CimaRESUMO
OBJECTIVE: To provide a review of the clinical data supporting the use of sunitinib (Sutent), a multitargeted, small molecule, tyrosine kinase inhibitor, with focus on its approved indication for the treatment of advanced renal cell carcinoma in patients with metastatic disease requiring drug therapy. DATA SOURCE: : A MEDLINE search of the medical literature was conducted using the terms 'sunitinib' and 'SU11248'. References from the articles were reviewed and relevant sources were included. DATA SUMMARY: The introduction of dual tyrosine kinase receptor inhibitors is a novel approach to treating advanced metastatic renal cell carcinoma (mRCC) by preventing angiogenesis and tumor growth. Based on its ability to inhibit several targets involved in angiogenesis and endothelial cell proliferation, sunitinib offers patients with mRCC an alternative for treatment. A recent Phase III study evaluating sunitinib as first-line therapy showed a significant difference when compared to interferonalfa (IFN-alpha) for a progression-free survival of 11 months in the sunitinib arm and 5 months in the IFN-alpha arm (hazard ratio 0.42; 95% CI 0.32-0.54; P50.001). Two Phase II trials determined sunitinib was effective as second-line therapy in mRCC patients who failed previous cytokine treatment. Partial response rates were 40% (95% CI 28%-53%) and 34% (95% CI 25%-44%). Multiple ongoing trials are currently underway to evaluate sunitinib for first-line therapy in mRCC.
