RESUMEN
New approaches are needed to overcome intrinsic therapy resistance in glioblastoma (GBM). Because GBMs exhibit sexual dimorphism and are reported to express steroid hormone receptors, we reasoned that signaling through the androgen receptor (AR) could mediate therapy resistance in GBM, much as it does in AR-positive prostate and breast cancers. We found that nearly half of GBM cell lines, patient-derived xenografts (PDX), and human tumors expressed AR at the transcript and protein level-with expression levels overlapping those of primary prostate cancer. Analysis of gene expression datasets also revealed that AR expression is higher in GBM patient samples than normal brain tissue. Multiple clinical-grade antiandrogens slowed the growth of and radiosensitized AR-positive GBM cell lines and PDXs in vitro and in vivo Antiandrogens blocked the ability of AR-positive GBM PDXs to engage adaptive transcriptional programs following radiation and slowed the repair of radiation-induced DNA damage. These results suggest that combining blood-brain barrier permeable antiandrogens with radiation may have promise for patients with AR-positive GBMs.
Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Glioblastoma/tratamiento farmacológico , Receptores Androgénicos/metabolismo , Antagonistas de Andrógenos/farmacología , Animales , Femenino , Humanos , Ratones , Ratones SCIDRESUMEN
In this study, we compared the effectiveness of armoise and clove bud essential oils (EOs) and the combination of low concentrations of copper (Cu) and lactic acid (LA) against E. coli O157:H7 in a laboratory medium. Three strains of Escherichia coli O157:H7 (ATCC700599, ATCC51659, and ATCC43895) were used in this study. Antibacterial activity was determined by measuring the turbidity of a broth medium and by determination of bacterial populations. Our results showed that armoise (0.15% v/v), clove bud (0.1% v/v) EOs, or Cu (50 ppm) in combination with LA (0.2% v/v) caused a minimum 5.0 log reduction of E. coli O157:H7 in the laboratory medium. Cu in combination with LA may thus be preferable to EOs in food in order to control the growth of foodborne pathogens. In addition, the combination treatment of Cu and LA could provide the food industry with a practical approach to reducing the risk of foodborne pathogens.