Sarcomas are mesenchymal cancers with poor prognosis, representing about 20% of all solid malignancies in children, adolescents, and young adults. Radio- and chemoresistance are common features of sarcomas warranting the search for novel prognostic and predictive markers. GARP/LRRC32 is a TGF-β-activating protein that promotes immune escape and dissemination in various cancers. However, if GARP affects the tumorigenicity and treatment resistance of sarcomas is not known. We show that GARP is expressed by human osteo-, chondro-, and undifferentiated pleomorphic sarcomas and is associated with a significantly worse clinical prognosis. Silencing of GARP in bone sarcoma cell lines blocked their proliferation and induced apoptosis. In contrast, overexpression of GARP promoted their growth in vitro and in vivo and increased their resistance to DNA damage and cell death induced by etoposide, doxorubicin, and irradiation. Our data suggest that GARP could serve as a marker with therapeutic, prognostic, and predictive value in sarcoma. We propose that targeting GARP in bone sarcomas could reduce tumour burden while simultaneously improving the efficacy of chemo- and radiotherapy.
Cancer is among the leading causes of mortality worldwide. Current cancer therapies are associated with serious side effects, which further damage patients' health. Therefore, the search for new anticancer agents with no toxic effects on normal and healthy cells is of great interest. Recently, we and other groups have demonstrated that oleocanthal (OLC), a phenolic compound from extra virgin olive oil, exhibits antitumor activity in various tumor models. However, the underlying mechanisms and intracellular targets of OLC remain to be completely elucidated. This review summarizes the current advancers concerning the anticancer activity of OLC, with particular emphasis on the molecular signaling pathways modulated by this compound in different tumor cell types. The major mechanisms of action of OLC include modulation of the apoptotic pathway, the HGF/c-Met pathway, and the signal transducer and activator of transcription 3 signaling pathway, among others. Furthermore, OLC has synergistic effects with anticancer drugs in vitro. Also discussed are OLC bioavailability and its concentration in olive oil. Data summarized here will represent a database for more extensive studies aimed at providing information on molecular mechanisms against cancer induced by OLC.
En este artículo se explica el diseño de una estrategia de educación ambiental enmarcada en los modelos pedagógicos auto estructurantes que utiliza la lúdica como herramienta esencial para construir conceptos e incentivar la investigación. La estrategia se llevó a la práctica con 40 estudiantes de primaria y bachillerato de la Institución Educativa de Isla Fuerte, una localidad marginal afrodescendiente. Aunque no pudo aplicarse en su totalidad, las actividades realizadas permitieron hacer un análisis de la metodología y los resultados obtenidos. El ejercicio aprovechó la tradición oral de la comunidad, despertó la imaginación y la curiosidad, y logró interiorizar conceptos ambientales en los chicos. Aunque se cambiaron algunas actitudes apáticas hacia los problemas ambientales, y se despertó disposición y dedicación, es posible que se requiera tiempo para visibilizar los cambios de percepción alcanzados.
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