ABSTRACT
Introducción: La subunidad ácido-lábil (ALS) tiene un papel importante en los efectos endocrinos de los factores de crecimiento similares a la insulina (IGF) en tejidos diana. Históricamente ha recibido una atención limitada. El objetivo de nuestro estudio fue describir el rango normal de ALS en niños sanos y su relación con otros factores de crecimiento. Pacientes y métodos: Se diseñó un estudio descriptivo transversal. Se recopilaron datos sobre edad, altura, índice de masa corporal, edad gestacional, antropometría al nacer y niveles séricos de ALS, IGF1 e IGFBP3 de niños sanos de 2 a 15años con estatura estándar. Los niveles de ALS, IGF1 e IGFBP3 se midieron mediante ELISA. Se utilizaron modelos de normalización GAMLSS para la estandarización de variables. Resultados: Se recogieron muestras de 446 niños. En niños prepúberes, los niveles de ALS, IGF1 e IGFBP3 se correlacionaron de manera positiva en ambos sexos y con la edad (p<0,01). Los niveles de ALS, IGF1 e IGFBP3 y la relación molar IGF1/IGFBP3 fueron significativamente diferentes entre ambos sexos y más altos en los niños puberales (p<0,01). Se realizaron gráficas de normalidad por género para cada uno de los componentes del complejo ternario y para las relaciones molares IGF1/IGFBP3 e IGFBP3/ALS. Además, se construyeron fórmulas modelo para calcular el Z Score según la edad y el sexo. ConclusionesEste estudio podría determinar valores de referencia específicos por edad y sexo para IGF1, IGFBP3, ALS, IGF1/IGFBP3 e IGFBP3/ALS en niños españoles y parece establecer la relación entre edad, sexo y estadio puberal. (AU)
Introduction: The acid-labile subunit (ALS) plays an important role in the endocrine effects of insulin-like growth factors (IGFs) on target tissues. Historically, it has attracted limited attention. The aim of our study was to describe the normal range of ALS in healthy children and its association with other growth factors. Patients and methods: We designed a cross-sectional descriptive study. We collected data on age, height, body mass index, gestational age, anthropometry at birth and serum levels of ALS, IGF1 and IGFBP3 in healthy children aged 2-15years with a normal height. The levels of ALS, IGF1 and IGFBP3 were measured by ELISA. We fitted GAMLSS normalization models to standardize the variables. Results: Samples were collected from 446 children. In prepubertal children, the levels of ALS, IGF1 and IGFBP3 were positively correlated in both sexes and with age (P<.01). We found significant differences in the levels of ALS, IGF1 and IGFBP3 and the IGF1/IGFBP3 molar ratio between the sexes and higher levels in pubertal boys (P<.01). We generated normal probability plots for each sex for each of the components of the ternary complex and for the IGF1/IGFBP3 and IGFBP3/ALS molar ratios. In addition, we extracted equations from the models for the calculation of z-scores for age and sex. Conclusions: This study may contribute to age- and sex-specific reference values for IGF1, IGFBP3 and ALS levels and IGF1/IGFBP3 and IGFBP3/ALS ratios in Spanish children and suggests an association between age, sex and pubertal stage. (AU)
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Insulin-Like Growth Factor I , Insulin-Like Growth Factor Binding Protein 3 , Epidemiology, Descriptive , Cross-Sectional Studies , Spain , Body Mass IndexABSTRACT
INTRODUCTION: The acid-labile subunit (ALS) plays an important role in the endocrine effects of insulin-like growth factors (IGFs) on target tissues. Historically, it has attracted limited attention. The aim of our study was to describe the normal range of ALS in healthy children and its association with other growth factors. PATIENTS AND METHODS: We designed a cross-sectional descriptive study. We collected data on age, height, body mass index, gestational age, anthropometry at birth and serum levels of ALS, IGF1 and IGFBP3 in healthy children aged 2-15 years with a normal height. The levels of ALS, IGF1 and IGFBP3 were measured by ELISA. We fitted GAMLSS normalization models to standardize the variables. RESULTS: Samples were collected from 446 children. In prepubertal children, the levels of ALS, IGF1 and IGFBP3 were positively correlated in both sexes and with age (P < .01). We found significant differences in the levels of ALS, IGF1 and IGFBP3 and the IGF1/IGFBP3 molar ratio between the sexes and higher levels in pubertal boys (P < .01). We generated normal probability plots for each sex for each of the components of the ternary complex and for the IGF1/IGFBP3 and IGFBP3/ALS molar ratios. In addition, we extracted equations from the models for the calculation of z-scores for age and sex. CONCLUSIONS: This study may contribute age- and sex-specific reference values for IGF1, IGFBP3 and ALS levels and IGF1/IGFBP3 and IGFBP3/ALS ratios in Spanish children and suggests an association between age, sex, and pubertal stage.
Subject(s)
Reference Values , Male , Infant, Newborn , Female , Humans , Child , Child, Preschool , Adolescent , Spain , Cross-Sectional Studies , Gestational AgeABSTRACT
â¢OGM surgery is much more complex than a simple debate of "from above or from below" (transcranial vs endoscopic).â¢Lateral Sub-frontal and Superior Interhemispheric seem the most effective, superior and versatile approaches for OGM.â¢Minimally Invasive Transcranial approaches showed no inferiority in OGM sized <4 âcm.â¢Endoscopic Endonasal Approaches showed inferior results in surgical and in functional outcomes for OGM.
ABSTRACT
Diagnosis and classification of gliomas mostly relies on histopathology and a few genetic markers. Here we interrogated microarray gene expression profiles (GEP) of 268 diffuse astrocytic gliomas-33 diffuse astrocytomas (DA), 52 anaplastic astrocytomas (AA) and 183 primary glioblastoma (GBM)-based on multivariate analysis, to identify discriminatory GEP that might support precise histopathological tumor stratification, particularly among inconclusive cases with II-III grade diagnosed, which have different prognosis and treatment strategies. Microarrays based GEP was analyzed on 155 diffuse astrocytic gliomas (discovery cohort) and validated in another 113 tumors (validation set) via sequential univariate analysis (pairwise comparison) for discriminatory gene selection, followed by nonnegative matrix factorization and canonical biplot for identification of discriminatory GEP among the distinct histological tumor subtypes. GEP data analysis identified a set of 27 genes capable of differentiating among distinct subtypes of gliomas that might support current histological classification. DA + AA showed similar molecular profiles with only a few discriminatory genes overexpressed (FSTL5 and SFRP2) and underexpressed (XIST, TOP2A and SHOX2) in DA vs AA and GBM. Compared to DA + AA, GBM displayed underexpression of ETNPPL, SH3GL2, GABRG2, SPX, DPP10, GABRB2 and CNTN3 and overexpression of CHI3L1, IGFBP3, COL1A1 and VEGFA, among other differentially expressed genes.
Subject(s)
Astrocytoma/genetics , Brain Neoplasms/genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Astrocytoma/diagnosis , Brain Neoplasms/diagnosis , Discriminant Analysis , Female , Humans , Linear Models , Male , Middle Aged , Multivariate Analysis , Mutation , Oligonucleotide Array Sequence Analysis , Signal Transduction , SoftwareABSTRACT
BACKGROUND: The prognostic impact of the expression profile of genes recurrently amplified in glioblastoma multiforme (GBM) remains controversial. METHODS: We investigated the RNA gene expression profile of epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4), murine doble minute 4 (MDM4), and platelet derived growth factor receptor alpha (PDGFRA) in 83 primary GBM tumors vs. 42 normal brain tissue samples. Interphase FISH (iFISH) analysis for the four genes, together with analysis of intragenic deletions in EGFR and PDGFRA, were evaluated in parallel at the DNA level. As validation cohort, publicly available RNA gene expression data on 293 samples from 10 different GBM patient series were also studied. RESULTS: At the RNA level, CDK4 was the most frequently overexpressed gene (90%) followed by EGFR (58%) and PDGFRA (58%). Chromosome 7 copy number alterations, i.e., trisomy (49%) and polysomy (44%), showed no clear association with EGFR gene expression levels. In turn, intragenic EGFR deletions were found in 39 patients (47%), including EGFRvIII (46%) in association with EGFRvIVa (4%), EGFRvII (2%) or other EGFR deletions (3%) and PDGFRA deletion of exons 8-9 was found in only two tumors (2%). CONCLUSIONS: Overall, none of the gene expression profiles and/or intragenic EGFR deletions showed a significant impact on overall survival of GBM supporting the notion that other still unraveled features of the disease might play a more relevant prognostic role in GBM.
