RESUMO
Tsukamurella spp. are gram-positive rods that can be isolated from the environment in soil and moist areas. In rare instances, they are known to cause infections in immunocompromised hosts. We present the first reported case of Tsukamurella endocarditis in an immunocompromised patient who was successfully treated with a 6-week course of imipenem and trimethoprim-sulfamethoxazole.
Assuntos
Actinobacteria/isolamento & purificação , Endocardite Bacteriana/diagnóstico , Hospedeiro Imunocomprometido , Actinobacteria/genética , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antineoplásicos/uso terapêutico , Diagnóstico Diferencial , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/microbiologia , Feminino , Humanos , Imipenem/administração & dosagem , Imipenem/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoRESUMO
The CD95/CD95L receptor-ligand system is mainly recognised in the induction of apoptosis. However, it has also been shown that CD95L is over-expressed in many cancer types where it modulates immune-evasion and together with its receptor CD95 promotes tumour growth. Here, we show that CD95 surface modification of relatively large microparticles >0.5 µm in diameter, including those made from biodegradable polylactic-co-glycolic acid (PLGA), enhances intracellular uptake by a range of CD95L expressing cells in a process akin to phagocytosis. Using this approach we describe the intracellular uptake of microparticles and agent delivery in neurons, medulloblastoma, breast and ovarian cancer cells in vitro. CD95 modified paclitaxel-loaded PLGA microparticles are shown to be significantly more effective compared to conventional paclitaxel therapy (Taxol) at the same dose in subcutaneous medulloblastoma (∗∗∗P < 0.0001) and orthotopic ovarian cancer xenograft models where a >65-fold reduction in tumour bioluminescence was measured after treatment (∗P = 0.012). This drug delivery platform represents a new way of manipulating the normally advantageous tumour CD95L over-expression towards a therapeutic strategy. CD95 functionalised drug carriers could contribute to the improved function of cytotoxics in cancer, potentially increasing drug targeting and efficacy whilst reducing toxicity.