Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures

The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s) at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK) signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by 'RTK swapping' by interfering with PDGFRβ phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in cancer cells reveal them to be promising anticancer agents for further investigation.

Centres diürns d'atenció a la gent gran: grau de satisfacció dels usuaris i familiars

Estudi descriptiu sobre els centres de dia i centres de serveis per a la gent gran, dos recursos que ofereixen atenció diürna, i sobre la satisfacció que comporta assistir a un o a l’altre. OBJECTIUS. Descriure i comparar dos models d’atenció diürna per a la gent gran, i els graus de satisfacció d’aquells que els utilitzen. MÈTODES. Estudi multicèntric descriptiu, de disseny és transversal. Portat a terme entre els mesos d’abril i juny de 2011, en set centres de serveis i un centre de dia, ha inclòs un total de 296 persones. S’ha fet una valoració del grau de satisfacció d’usuaris i familiars mitjançant una enquesta de disseny propi. RESULTATS. Els centres de dia, que es troben situats en zones urbanes, ofereixen un únic servei (servei d’estada), on el 41,94% de les persones tenen una elevada dependència. Els centres de serveis, que estan situats en zones rurals, ofereixen serveis d’estada, ambulatoris, tallers i atenció a domicili, i el 25,58% de les persones mostra una dependència elevada. El grau de satisfacció en els dos tipus de centres és elevada tant en famílies 87,63%, com en usuaris 96.5% . CONCLUSIÓ. Són dos models que tenen similituds, però ofereixen diferents tipus de serveis. Creats amb més de 15 anys de diferència, és possible que el centre de serveis acabi sent l’evolució natural del centre de dia.

Indicadores sociales y psicosociales de calidad de vida de las personas mayores en un municipio = Social and psychosocial quality of life indicators of older persons in a municipality

A research about the quality of life of the older persons of a municipality starting from the analysis of the perceptions, evaluations and expectations related to concrete spheres of their lives (familiar characteristics, housing, health, nearby environment, activities, needs and dependencies and persons helping them to satisfy needs) is presented. Answers to 1988 questionnaires obtained from two representative samples of older per - sons living in private homes in the city have been analysed: persons over 65 years old and a specific one composed by a sub-sample of the general one, with persons over 75 years living alone. Data shaping contextual indicators related to housing have been analysed. The auto - nomy to drive and the evaluation of on’s health seem to be positive indicators to take in account while sutying quality of life at these ages. Sentinel indicators of the physical and relational conditions in the family and indicators of dependency are analysed as well. The evaluations of the older persons about their own life conditions are also analysed through psychosocial indicators connected to housing, nearby environmenent, their activities andincomes. The results obtained are applicable in order to improve the decision making process in social intervention programmes developed in the field of ageing aiming to take into account their perspectives