RESUMO
Ewing sarcoma (EWS) is a malignant tumor arising in bone or soft tissue that occurs in adolescent and young adult patients as well as adults later in life. Although non-metastatic EWS is typically responsive to treatment when newly diagnosed, relapsed cases have an unmet need for which no standard treatment approach exists. Recent phase III clinical trials for EWS comparing 7 vs 5 chemotherapy drugs have failed to improve survival. To extend the durability of remission for EWS, we investigated 3 non-chemotherapy adjuvant therapy drug candidates to be combined with chemotherapy. The efficacy of these adjuvant drugs was investigated via anchorage-dependent growth assays, anchorage-independent soft-agar colony formation assays and EWS xenograft mouse models. Enoxacin and entinostat were the most effective adjuvant drug in both long-term in vitro and in vivo adjuvant studies. In the context that enoxacin is an FDA-approved antibiotic, and that entinostat is an investigational agent not yet FDA-approved, we propose enoxacin as an adjuvant drug for further preclinical and clinical investigation in EWS patients.
Assuntos
Tumores Neuroectodérmicos Primitivos Periféricos , Sarcoma de Ewing , Humanos , Animais , Camundongos , Sarcoma de Ewing/tratamento farmacológico , Enoxacino , Benzamidas , Adjuvantes Imunológicos , Adjuvantes Farmacêuticos , Modelos Animais de Doenças , Proteína Supressora de Tumor p53RESUMO
The method employed for depositing nanostructures of conducting polymers dictates potential uses in a variety of applications such as organic solar cells, light-emitting diodes, electrochromics, and sensors. A simple and scalable film fabrication technique that allows reproducible control of thickness, and morphological homogeneity at the nanoscale, is an attractive option for industrial applications. Here we demonstrate that under the proper conditions of volume, doping, and polymer concentration, films consisting of monolayers of conducting polymer nanofibers such as polyaniline, polythiophene, and poly(3-hexylthiophene) can be produced in a matter of seconds. A thermodynamically driven solution-based process leads to the growth of transparent thin films of interfacially adsorbed nanofibers. High quality transparent thin films are deposited at ambient conditions on virtually any substrate. This inexpensive process uses solutions that are recyclable and affords a new technique in the field of conducting polymers for coating large substrate areas.