Aplicación de anticuerpos monoclonales en oncología

Los anticuerpos monoclonales representan una pieza fundamental en el arsenal terapéutico en oncología. Estos compuestos biológicos de alta complejidad han logrado mejorar la supervivencia de los pacientes con cáncer. Entre los clásicos se encuentran: rituximab, bevacizumab, cetuximab, trastuzumab utilizados a diario en nuestro medio. En la última década, la inmunoterapia se ha posicionado como una terapia eficaz para neoplásias de pronóstico adverso como el melanoma, cáncer de pulmón y renal. En el futuro próximo, los nuevos conjugados de anticuerpos y la terapia con células T quiméricas se presentarán como paradigmas de terapias promisorias en el manejo del cáncer.

Study of Caffeine-Loaded Gelatin Nanoparticles for Treatment of Melanoma and Fibroblast Cells

In this work, we aimed to study the effect of caffeine-loaded gelatin nanoparticles on melanoma cells and fibroblast cells. The B16F10 murine melanoma cells and L929 fibroblast cells were treated with a different dilution ratio of caffeine-loaded gelatin nanoparticles for 24, 48, and 72 h. The cell assay results showed that treatment with caffeine-loaded gelatin nanoparticles (25 % and 50 %) effectively inhibited the proliferation, viability, and migration ability of B16F10 melanoma cells at 48 and 72 h. Moreover, we also found that the cell apoptosis of B16F10 melanoma cells was induced by treatment of 12.5, 25, and 50 % caffeine-loaded gelatin nanoparticles. In the meantime, for L929 fibroblast cells, there was no significant cell cytotoxic effects observed with identical treatment. In summary, the caffeine-loaded gelatin nanoparticles induced apoptotic process inhibited cell viability and migration ability of melanoma cells and could be an alternative therapy for melanoma cancer.

Processing body dynamics drive non-genetic MEK inhibitors tolerance by fine-tuning KRAS and NRAS translation

BackgroundOveractivation of the Mitogen-activated protein kinase (MAPK) pathway is a critical driver of many human cancers. However, therapies that target this pathway have only been effective in a few cancers, as cancers inevitably end up developing resistance. Puzzling observations have suggested that MAPK targeting in tumor fails because of an early compensatory RAS overexpression, but through unexplained mechanisms.MethodsLung, breast, and melanoma cancer cells were incubated with MEK inhibitors (MEKi). Kinetics of expression of KRAS, NRAS mRNA and proteins and processing bodies (PBs) proteins were followed overtime by immunoblot and confocal studies.ResultsHere, we identified a novel mechanism of drug tolerance for MEKi involving PBs essential proteins like DDX6 or LSM14A. MEKi promoted the translation of KRAS and NRAS oncogenes, which in turn triggered BRAF phosphorylation. This overexpression, which occurred in the absence of neo-transcription, depended on PBs dissolution as a source of RAS mRNA reservoir. In addition, in response to MEKi removal, we showed that the process was dynamic since the PBs quickly reformed, reducing MAPK signaling. These results underline a dynamic spatiotemporal negative feedback loop of MAPK signaling via RAS mRNA sequestration. Furthermore, in long-tolerant cells, we observed a LSM14A loss of expression that promoted a low PBs number phenotype together with strong KRAS and NRAS induction capacities.ConclusionsAltogether we describe here a new intricate mechanism involving PB, DDX6 and LSM14A in the translation regulation of essential cellular pathways that pave the way for future therapies altering PBs dissolution to improve cancer targeted-drug therapies.

Green synthesis of bimetallic ZnO–CuO nanoparticles and their cytotoxicity properties

In this study, a simple and green strategy was reported to prepare bimetallic nanoparticles (NPs) by the combination of zinc oxide (ZnO) and copper oxide (CuO) using Sambucus nigra L. extract. The physicochemical properties of these NPs such as crystal structure, size, and morphology were studied by X-ray diffraction (XRD), field emission gun scanning electron microscopy (FEG-SEM), and transmission electron microscopy (TEM). The results suggested that these NPs contained polygonal ZnO NPs with hexagonal phase and spherical CuO NPs with monoclinic phase. The anticancer activity of the prepared bimetallic NPs was evaluated against lung and human melanoma cell lines based on MTT assay. As a result, the bimetallic ZnO/CuO NPs exhibited high toxicity on melanoma cancer cells while their toxicity on lung cancer cells was low.