Search results for " FEM"
showing 10 items of 2305 documents
Noncanonical GLI1 signaling promotes stemness features and in vivo growth in lung adenocarcinoma
2016
Aberrant Hedgehog/GLI signaling has been implicated in a diverse spectrum of human cancers, but its role in lung adenocarcinoma (LAC) is still under debate. We show that the downstream effector of the Hedgehog pathway, GLI1, is expressed in 76% of LACs, but in roughly half of these tumors, the canonical pathway activator, Smoothened, is expressed at low levels, possibly owing to epigenetic silencing. In LAC cells including the cancer stem cell compartment, we show that GLI1 is activated noncanonically by MAPK/ERK signaling. Different mechanisms can trigger the MAPK/ERK/GLI1 cascade including KRAS mutation and stimulation of NRP2 by VEGF produced by the cancer cells themselves in an autocrin…
PTEN status is a crucial determinant of the functional outcome of combined MEK and mTOR inhibition in cancer
2017
AbstractCombined MAPK/PI3K pathway inhibition represents an attractive, albeit toxic, therapeutic strategy in oncology. Since PTEN lies at the intersection of these two pathways, we investigated whether PTEN status determines the functional response to combined pathway inhibition. PTEN (gene, mRNA, and protein) status was extensively characterized in a panel of cancer cell lines and combined MEK/mTOR inhibition displayed highly synergistic pharmacologic interactions almost exclusively in PTEN-loss models. Genetic manipulation of PTEN status confirmed a mechanistic role for PTEN in determining the functional outcome of combined pathway blockade. Proteomic analysis showed greater phosphoprote…
De novo mutations in the X-linked TFE3 gene cause intellectual disability with pigmentary mosaicism and storage disorder-like features
2020
IntroductionPigmentary mosaicism (PM) manifests by pigmentation anomalies along Blaschko’s lines and represents a clue toward the molecular diagnosis of syndromic intellectual disability (ID). Together with new insights on the role for lysosomal signalling in embryonic stem cell differentiation, mutations in the X-linked transcription factor 3 (TFE3) have recently been reported in five patients. Functional analysis suggested these mutations to result in ectopic nuclear gain of functions.Materials and methodsSubsequent data sharing allowed the clustering of de novo TFE3 variants identified by exome sequencing on DNA extracted from leucocytes in patients referred for syndromic ID with or with…
Dietary intake and major food sources of polyphenols in people with type 2 diabetes: The TOSCA.IT Study
2018
Purpose: Proper evaluation of polyphenols intake at the population level is a necessary step in order to establish possible associations with health outcomes. Available data are limited, and so far no study has been performed in people with diabetes. The aim of this work was to document the intake of polyphenols and their major food sources in a cohort of people with type 2 diabetes and in socio-demographic subgroups. Methods: We studied 2573 men and women aged 50–75 years. Among others, anthropometry was measured by standard protocol and dietary habits were investigated by food frequency questionnaire (EPIC). The intake of polyphenols was evaluated using US Department of Agriculture and Ph…
Aging-associated genes and let-7 microRNAs: a contribution to myogenic program dysregulation in oculopharyngeal muscular dystrophy
2019
Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disease caused by an abnormal (GCN) triplet expansion within the polyadenylate-binding protein nuclear 1 gene and consequent mRNA pr...
Shared DNA methylation signatures in childhood allergy: The MeDALL study
2021
Contains fulltext : 232514.pdf (Publisher’s version ) (Open Access) BACKGROUND: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema. OBJECTIVE: We sought to identify DNA methylation profiles associated with childhood allergy. METHODS: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discove…
Real-World Hypertension Prevalence, Awareness, Treatment, and Control in Adult Diabetic Individuals: An Italian Nationwide Epidemiological Survey
2021
Introduction: Hypertesion is the leading cause of morbidity and mortality, worldwide, and its prevalence has been increasing in several countries, including Italy. Aims: To assess hypertension prevalence, awareness, treatment, and control in a real-world sample of adults with self-reported diabetes compared with nondiabetic individuals. Methods: Following the 2018 World Hypertension Day, a nationwide, cross-sectional epidemiological survey on cardiovascular risk factors (“Abbasso la Pressione!”) in 3956 Italian pharmacies enrolled 47217 self-presenting volunteers (≥ 18 years). Participants underwent standardized blood pressure (BP) measurements and answered a questionnaire on cardiovascular…
Switching to dual/monotherapy determines an increase in CD8+ in HIV-infected individuals: An observational cohort study
2018
Background The CD4/CD8 ratio has been associated with the risk of AIDS and non-AIDS events. We describe trends in immunological parameters in people who underwent a switch to monotherapy or dual therapy, compared to a control group remaining on triple antiretroviral therapy (ART). Methods We included patients in Icona who started a three-drug combination ART regimen from an ART-naïve status and achieved a viral load ≤ 50 copies/mL; they were subsequently switched to another triple or to a mono or double regimen. Standard linear regression at fixed points in time (12-24 months after the switch) and linear mixed model analysis with random intercepts and slopes were used to compare CD4 and CD8…
Thyroid Cancer in the Pediatric Age in Sicily: Influence of the Volcanic Environment.
2017
Background/Aim: Pediatric thyroid cancer (TC) is rare but its incidence is increasing. We analyzed incidence and characteristics of pediatric TC in Sicily and comparatively evaluated data from the volcanic and non-volcanic areas. Materials and Methods: All incident pediatric (0-19 years) TCs in Sicily between 2002-2009 were analyzed for the area of residence and compared to data for adults. Results: A total of 54 differentiated TCs (DTC) and nine medullary TCs were diagnosed in Sicily in children between 2002-2009. DTC age standardized rate for the world population (ASRw) was 0.8/105 in females and 0.2/105 in males, with a higher incidence in the volcanic area (ASRw=1.4/105 in females, 0.5/…
Geographical variability in survival of European children with central nervous system tumours
2017
Survival for childhood central nervous system (CNS) tumours varies across Europe, partly because of the difficulty of distinguishing malignant from non-malignant disease. This study examines bias in CNS tumours survival analysis to obtain the reliable and comparable survival figures. We analysed survival data for about 15, 000 children (age <15) diagnosed with CNS between 2000 and 2007, from 71 population- based cancer registries in 27 countries. We selected high- quality data based on registry- specific data quality indicators and recorded observed 1-year and 5-year survival by countries and CNS entity. We provided age- adjusted survival and used a Cox model to calculate the hazard ratios …