RESUMO
Immune checkpoint inhibitors have improved the clinical management of some cancer cases, yet patients still fail to respond to immunotherapy. Dysregulated metabolism is a common feature of many cancers, and metabolites are known to modulate functions in cancer cells. To identify potential metabolic pathways involved in anti-tumor immune response, we employed a metabolic inhibitor-based drug screen in human lung cancer cell lines and examined expression changes in a panel of immune regulator genes. Notably, pharmacologic inhibition of dihydrofolate reductase (DHFR) downregulated cancer cell expression of cluster of differentiation 24 (CD24), an anti-phagocytic surface protein. Genetic modulation of DHFR resulted in decrease of CD24 expression, whereas tetrahydrofolate, the product of DHFR, enhanced CD24 expression. DHFR inhibition and the consequent CD24 decrease enhanced T cell-mediated tumor cell killing, whereas replenishment of DHFR or CD24 partially mitigated the immune-mediated tumor cell killing that resulted from methotrexate treatment in cancer cells. Moreover, publicly available clinical data analyses further revealed the link between DHFR, CD24, and the antitumor immune response in lung cancer patients. Our study highlights a novel connection between folate metabolism and the anti-tumor immune response and partially interprets how DHFR inhibitors lead to clinical benefits when combined with cancer immunotherapy agents.
RESUMO
Objetivo: determinar la motivación laboral hacia la investigación científica que presenta el profesional de enfermería asistencial en el Hospital Nacional Arzobispo Loayza. Material y método: estudio descriptivo de corte transversal, constituido por una muestra de 211 profesionales enfermeros que cumplieron con los criterios de selección. Se aplicó un cuestionario tipo Likert que comprende 24 ítems, el cual fue validado mediante juicio de expertos y prueba piloto. La información se procesó y analizó en el software estadístico SPSS versión 21 para obtener tablas de frecuencias absolutas seg£n la variable requerida. Resultados: un 66.3 por ciento indica sentirse motivado a realizar investigación científica como una forma de alcanzar el crecimiento profesional, así como un 43.6 por ciento no realiza investigación porque afirma que implica mayor responsabilidad en su actividad profesional. Además, un 46.9 por ciento del profesional de enfermería afirma que el ambiente físico donde labora no es el adecuado para realizar investigación científica. Conclusiones: la motivación laboral intrínseca está relacionada principalmente con el desarrollo personal, el logro y el crecimiento profesional; y los indicadores con mayor porcentaje obtenido de la motivación laboral extrínseca son condiciones del ambiente físico, el bajo salario, la falta de recursos materiales, y la sobrecarga laboral dentro del horario de trabajo quienes dificultan realizar investigación.
Objective: To determine the work motivation towards the scientific research presented by the professional nursing care center at National Hospital. Material and Method: A descriptive cross-sectional study, a sample consisting of 203 professional nurses who met the selection criteria. Likert questionnaire comprising of 24 items, which was validated by an expert opinion and the pilot test was applied. The information is processed and analyzed in the statistical software SPSS version 21 for tables of absolute frequencies to the required variables. Results: 66.3 percent of the report felt motivated to conduct scientific research as a way to achieve professional growth and 43.6 percent was no conducted because it said that it implies greater responsibility for their work. In addition, 46.9 percent of the nurses say that the physical environment where they work is not adequate for scientific research. Conclusions: The intrinsic work motivation is primarily related to personal development, achievement and professional growth; indicators obtained with the highest percentage of extrinsic work motivation are conditions of the physical environment, low wages, lack of material resources, and the work overload of the difficult work schedule of than who conducted the research.