ABSTRACT
The role of progenitor/stem cells in pituitary tumorigenesis, resistance to pharmacological treatments and tumor recurrence is still unclear. This study investigated the presence of progenitor/stem cells in non-functioning pituitary tumors (NFPTs) and tested the efficacy of dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists to inhibit in vitro proliferation. They found that 70% of 46 NFPTs formed spheres co-expressing stem cell markers, transcription factors (DAX1, SF1, ERG1) and gonadotropins. Analysis of tumor behavior showed that spheres formation was associated with tumor invasiveness (OR = 3,96; IC: 1.05-14.88, p = 0.036). The in vitro reduction of cell proliferation by DRD2 and SSTR2 agonists (31 ± 17% and 35 ± 13% inhibition, respectively, p < 0.01 vs. basal) occurring in about a half of NFPTs cells was conserved in the corresponding spheres. Accordingly, these drugs increased cyclin-dependent kinase inhibitor p27 and decreased cyclin D3 expression in spheres. In conclusion, they provided further evidence for the existence of cells with a progenitor/stem cells-like phenotype in the majority of NFPTs, particularly in those with invasive behavior, and demonstrated that the antiproliferative effects of dopaminergic and somatostatinergic drugs were maintained in progenitor/stem-like cells.
Subject(s)
Carcinogenesis/genetics , Neoplasm Recurrence, Local/drug therapy , Pituitary Neoplasms/drug therapy , Receptors, Dopamine D2/genetics , Receptors, Somatostatin/genetics , Adult , Carcinogenesis/drug effects , Cell Proliferation/drug effects , Cyclin D3/biosynthesis , Cyclin-Dependent Kinase Inhibitor p27/biosynthesis , DAX-1 Orphan Nuclear Receptor/biosynthesis , Dopamine Agents/administration & dosage , Drug Resistance, Neoplasm/genetics , ERG1 Potassium Channel/biosynthesis , Female , Gene Expression Regulation, Neoplastic/drug effects , Gonadotropins/biosynthesis , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Neoplastic Stem Cells/drug effects , Pituitary Neoplasms/genetics , Pituitary Neoplasms/pathology , RNA Splicing Factors/biosynthesis , Receptors, Dopamine D2/agonists , Receptors, Somatostatin/agonists , Spheroids, Cellular/drug effects , Spheroids, Cellular/pathologyABSTRACT
Numerous evidence suggests that vitamin D deficiency is implicated in the development of cardiovascular risk. It has been investigated the relationship between cardiovascular risk factors and vitamin D concentrations in 264 consecutive workers from Centro Obesità e Lavoro della Clinica del Lavoro di Milano. For these studies, glicometaboliche analysis, anthropometric measurements and impedance evalutation were performed and questionnaires to estimate nutrient levels in the diet were administered. The levels of vitamin D are found to be deficient in 166 patients (less than 20 ng/mL), insufficient in 63 patients (less than 30 ng/mL) and optimal for the remaining 35 patients. A significant negative association was observed between the concentrations of vitamin D and cardiovascular risk factors (HOMA ratio and TG/HDL) ratios and BMI. Vitamin D is a cardiovascular risk factor "corrected" for example by changing the eating habits of workers.