Personalidade e bem-estar subjetivo na excelência profissional: validação de escalas junto de gestores portugueses

O presente estudo teve como objetivo a validação da Satisfaction With Life Scale (SWLS; Diener, Emmons, Larsen, & Griffin, 1985) e da Core Self-Evaluations Scale (CSES; Judge, Erez, Bono, & Thoresen, 2003) junto de gestores empresariais portugueses (N = 108). A escala SWLS avalia a componente cognitiva do bem-estar psicológico, isto é, a satisfação percebida face à qualidade das condições de vida. A CSES, centrada na valoração básica que a pessoa faz do seu self, abarca quatro dimensões de personalidade: autoestima, autoeficácia generalizada, neuroticismo e lócus de controlo. Os resultados encontrados sugerem que ambos os instrumentos apresentam índices adequados de precisão e que os constructos iniciais definidos pelos autores se mantêm parcialmente na estrutura dimensional das escalas nesta amostra portuguesa, havendo maior proximidade na SWLS. Foi observada, ainda, uma correlação positiva e estatisticamente significativa entre traços de personalidade avaliados pela CSES e a satisfação com a vida avaliada pela SWLS, em particular relativamente aos itens reportados à perceção de autoeficácia.

A glycolytic phenotype is associated with prostate cancer progression and aggressiveness: a role for Monocarboxylate Transporters as metabolic targets for therapy.

Metabolic adaptation is considered an emerging hallmark of cancer, whereby cancer cells exhibit high rates of glucose consumption with consequent lactate production. To ensure rapid efflux of lactate, most cancer cells express high levels of monocarboxylate transporters (MCTs), which therefore may constitute suitable therapeutic targets. The impact of MCT inhibition, along with the clinical impact of altered cellular metabolism during prostate cancer (PCa) initiation and progression, has not been described. Using a large cohort of human prostate tissues of different grades, in silico data, in vitro and ex vivo studies, we demonstrate the metabolic heterogeneity of PCa and its clinical relevance. We show an increased glycolytic phenotype in advanced stages of PCa and its correlation with poor prognosis. Finally, we present evidence supporting MCTs as suitable targets in PCa, affecting not only cancer cell proliferation and survival but also the expression of a number of hypoxia-inducible factor target genes associated with poor prognosis. Herein, we suggest that patients with highly glycolytic tumours have poorer outcome, supporting the notion of targeting glycolytic tumour cells in prostate cancer through the use of MCT inhibitors.

MET is required for the recruitment of anti-tumoural neutrophils

Mutations or amplification of the MET proto-oncogene are involved in the pathogenesis of several tumours, which rely on the constitutive engagement of this pathway for their growth and survival. However, MET is expressed not only by cancer cells but also by tumour-associated stromal cells, although its precise role in this compartment is not well characterized. Here we show that MET is required for neutrophil chemoattraction and cytotoxicity in response to its ligand hepatocyte growth factor (HGF). Met deletion in mouse neutrophils enhances tumour growth and metastasis. This phenotype correlates with reduced neutrophil infiltration to both the primary tumour and metastatic sites. Similarly, Met is necessary for neutrophil transudation during colitis, skin rash or peritonitis. Mechanistically, Met is induced by tumour-derived tumour necrosis factor (TNF)-a or other inflammatory stimuli in both mouse and human neutrophils. This induction is instrumental for neutrophil transmigration across an activated endothelium and for inducible nitric oxide synthase production upon HGF stimulation. Consequently, HGF/MET-dependent nitric oxide release by neutrophils promotes cancer cell killing, which abates tumour growth and metastasis. After systemic administration of a MET kinase inhibitor, we prove that the therapeutic benefit of MET targeting in cancer cells is partly countered by the pro-tumoural effect arising from MET blockade in neutrophils. Our work identifies an unprecedented role of MET in neutrophils, suggests a potential 'Achilles' heel' of MET-targeted therapies in cancer, and supports the rationale for evaluating anti-MET drugs in certain inflammatory diseases.