ABSTRACT
DEK is an oncoprotein involved in a variety of cellular functions, such as DNA repair, replication, and transcriptional control. DEK is preferentially expressed in actively proliferating and malignant cells, including melanoma cell lines in which DEK was previously demonstrated to play a critical role in proliferation and chemoresistance. Still, the impact of this protein in melanoma progression remains unclear. Thus, we performed a comprehensive analysis of DEK expression in different melanocytic tumors. The immunostaining results of 303 tumors demonstrated negligible DEK expression in benign lesions. Conversely, malignant lesions, particularly in metastatic cases, were largely positive for DEK expression, which was partially associated with genomic amplification. Importantly, DEK overexpression was correlated with histological features of aggressiveness in primary tumors and poor prognosis in melanoma patients. In conclusion, our study provides new insight into the involvement of DEK in melanoma progression, as well as proof of concept for its potential application as a marker and therapeutic target of melanoma.
Subject(s)
Biomarkers, Tumor/metabolism , Chromosomal Proteins, Non-Histone/metabolism , Gene Expression Regulation, Neoplastic , Melanoma/pathology , Oncogene Proteins/metabolism , Poly-ADP-Ribose Binding Proteins/metabolism , Biomarkers, Tumor/genetics , Cell Proliferation , Chromosomal Proteins, Non-Histone/genetics , Disease Progression , Female , Follow-Up Studies , Humans , Immunoenzyme Techniques , Lymphatic Metastasis , Male , Melanoma/genetics , Melanoma/metabolism , Middle Aged , Neoplasm Staging , Oncogene Proteins/genetics , Poly-ADP-Ribose Binding Proteins/genetics , Prognosis , Survival Rate , Tumor Cells, CulturedABSTRACT
The era of targeted therapy has introduced a new therapeutic perspective for melanoma patients. Treatment with BRAFV600 inhibitors has improved overall and disease-free survival in metastatic melanoma patients whose tumors harbor BRAFV600 mutations. Although the BRAFV600E mutation appears to have a critical role in tumor initiation, its expression during tumor progression remains controversial. In fact, various authors claim that BRAFV600E heterogeneity is evident in melanoma tumors. Herein, we investigated the pattern of BRAFV600E expression in matched primary and metastatic samples from 140 patients. Using a combination of real-time PCR and immunohistochemical analyses, we demonstrated that BRAFV600E expression is homogeneous in melanoma tumors and hypothesized that the heterogeneity described by others might be attributable to technical issues when molecular methods are used. We also demonstrated the high efficiency of the anti-BRAFV600E VE1 antibody for the detection of BRAFV600E mutations in melanoma tumors.
Subject(s)
Melanoma/genetics , Mutation , Proto-Oncogene Proteins B-raf/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , Male , Middle Aged , Real-Time Polymerase Chain ReactionABSTRACT
Dada la alta prevalencia de Diabetes Mellitus tipo 2 (DM2),se está llevando a cabo una investigación sobre la diabetes enEuropa y su prevención, mediante la intervención sobre estilosde vida modificables, conocido como Estudio DE_PLAN.Este trabajo forma parte de dicho estudio.Objetivo: evaluar la efectividad de un programa de intervenciónsobre cambios en los estilos de vida (dieta y ejercicio físico)para la prevención del desarrollo de DM2 en individuoscon alto riesgo.Material y método: estudio prospectivo longitudinal en poblaciónde 45 a 70 años, de ambos sexos, en la zona básica desalud de Arévalo. Se realizó un muestreo aleatorio por tarjetasanitaria, estratificado por zona: rural y semiurbana, calculándoseun tamaño muestral de 221 personas.El estudio se desarrolló en tres fases: Fase 1: cribado medianteescala de Findrisk, entrevista clínica, antropometría, analíticay PTOG. Tras la etapa de cribado, a las personas con Findrisk≥14 se les informa del programa de intervención Grupal; Fase2: intervención grupal: 4 talleres teórico-prácticos; y Fase 3:intervención continua. Refuerzo de la motivación y visitas clínicasanuales.Resultados: se excluyeron 21 por ser diabéticos. El Findriskfue ≤ 14 (alto riesgo) en 120 personas. Prevalencia de Diabetesdesconocida de 7,2%. De las 66 personas candidatas deambos sexos, aceptaron participar en el programa de intervención55 (83,3%) y lo terminaron 47. No hubo cambios significativosen el riesgo asociado al índice de masa corporal. Elporcentaje de inactividad inicial fue del 58%, del 11% después (..) (AU)
Given the high prevalence of type 2 Diabetes Mellitus (DM2),a research study on diabetes prevention is being conducted inEurope via an intervention on modifiable life styles known asPLAN Study. The work herein depicted is part of the saidEuropean study.Objective: to assess the effectiveness of an intervention programmeon changes in the life style (diet and physical exercise)to prevent the onset of DM2 in high-risk subjects.Material y methods: longitudinal prospective study in a populationsample aged 45 to 70, both genders, in a basic healtharea in Arévalo. A randomised sampling by health card wascarried out, which was subsequently stratified by area: ruraland semi-urban, with a sample size comprised of 221 people.The study was carried out in three phases: Phase 1: screeningby means of the Findrisk scale, clinical interview, anthropometrics,blood work and oral glucose tolerance test. Afterthe screening phase, subjects with a Findrisk ≥14 wereinformed of the group intervention programme; Phase 2: groupintervention, consisting of 4 theory-practical workshops; Phase3: continued intervention. Reinforcement of motivation andannual clinical visits.Results: 21 diabetic subjects were excluded. The Findrisk scorewas ≤ 14 (high risk) in 120 subjects. Prevalence of unknowndiabetes was 7,2%. Of the 66 candidates from both genders,55 (83,3%) accepted to participate in the programmeand 47 completed it. There were no (..) (AU)
