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Development of primary early-onset colorectal cancers due to biallelic mutations of the FANCD1/BRCA2 gene

2013

International audience; Fanconi anaemia (FA) is characterized by progressive bone marrow failure, congenital anomalies, and predisposition to malignancy. In a minority of cases, FA results from biallelic FANCD1/BRCA2 mutations that are associated with early-onset leukaemia and solid tumours. Here, we describe the clinical and molecular features of a remarkable family presenting with multiple primary colorectal cancers (CRCs) without detectable mutations in genes involved in the Mendelian predisposition to CRCs. We unexpectedly identified, despite the absence of clinical cardinal features of FA, a biallelic mutation of the FANCD1/BRCA2 corresponding to a frameshift alteration (c.1845_1846del…

AdultBiallelic MutationRNA Splicing[SDV]Life Sciences [q-bio]DNA Mutational AnalysisBiologymedicine.disease_causeArticleFrameshift mutationGeneticsmedicineHumansMissense mutationAge of OnsetGeneAllelesGenetics (clinical)BRCA2 ProteinGeneticsMutationPoint mutationComputational BiologyChromosome BreakageBRCA2 ProteinPedigree3. Good healthAmino Acid SubstitutionMutationFemaleRNA Splice SitesChromosome breakageColorectal NeoplasmsEuropean Journal of Human Genetics
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Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment.

2000

Hyperbaric oxygen (HBO) treatment of human subjects (i.e. exposure to 100% oxygen at a pressure of 2.5 ATA for a total period of 3 x 20 min) caused clear and reproducible DNA damage in lymphocytes, as detected with the comet assay (single cell gel electrophoresis). Induction of DNA damage was found only after the first HBO exposure and not after further treatments of the same individuals. Furthermore, blood taken 24 h after HBO treatment was significantly protected against the induction of DNA damage by hydrogen peroxide (H(2)O(2)) in vitro, indicating that adaptation occurred due to induction of antioxidant defenses. The cells were not significantly protected against the genotoxic effects …

AdultCancer ResearchDNA RepairDNA repairDNA damageCarbon-Oxygen LyasesBiologymedicine.disease_causeSuperoxide dismutasemedicineDNA-(Apurinic or Apyrimidinic Site) LyaseHumansLymphocytesDNA Polymerase betachemistry.chemical_classificationReactive oxygen speciesHyperbaric OxygenationSuperoxide DismutaseMembrane ProteinsGeneral MedicineHydrogen PeroxideCatalaseMolecular biologyDNA-(apurinic or apyrimidinic site) lyaseAdaptation PhysiologicalDeoxyribonuclease IV (Phage T4-Induced)Comet assayOxidative StresschemistryBiochemistryCatalaseEnzyme InductionHeme Oxygenase (Decyclizing)biology.proteinOxidative stressHeme Oxygenase-1DNA DamageCarcinogenesis
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DNA methylation patterns in newborns exposed to tobacco in utero

2015

[Background] Maternal smoking during pregnancy is a major risk factor for adverse health outcomes. The main objective of the study was to assess the impact of in utero tobacco exposure on DNA methylation in children born at term with appropriate weight at birth.

AdultEpigenomicsMothersPhysiologyBiologyGeneral Biochemistry Genetics and Molecular BiologyEpigenesis GeneticAdrenomedullinYoung Adultchemistry.chemical_compoundPregnancyRisk FactorsTobaccoCluster AnalysisHumansAdrenomedullin geneEpigeneticsNewbornsEpigenomicsMedicine(all)ImmunoassayDNA methylationBiochemistry Genetics and Molecular Biology(all)ResearchInfant NewbornGeneral MedicineMethylationFetal BloodGene Expression RegulationchemistryCpG siteMaternal ExposureIn uteroImmunologyDNA methylationCpG IslandsFemaleTobacco Smoke PollutionCotinineGenome-Wide Association StudyDNA hypomethylationJournal of Translational Medicine
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Genome-wide analysis reveals DNA methylation markers that vary with both age and obesity

2014

AbstractThe combination of the obesity epidemic and an aging population presents growing challenges for the healthcare system. Obesity and aging are major risk factors for a diverse number of diseases and it is of importance to understand their interaction and the underlying molecular mechanisms. Herein the authors examined the methylation levels of 27578 CpG sites in 46 samples from adult peripheral blood. The effect of obesity and aging was ascertained with general linear models. More than one hundred probes were correlated to aging, nine of which belonged to the KEGG group map04080. Additionally, 10 CpG sites had diverse methylation profiles in obese and lean individuals, one of which wa…

AdultGenetic Markersmedicine.medical_specialtyAgingAlpha-Ketoglutarate-Dependent Dioxygenase FTOGenome-wide association studyBiologyMicroarrayBioinformaticsEpigenesis GeneticGeneticsmedicineHumansEpigeneticsObesityKEGGTelomeraseAgedMedicinsk genetikGeneticsProteinsGeneral MedicineMethylationDNA MethylationMiddle Agedmedicine.diseaseObesityCpG siteDNA methylationMedical geneticsCpG IslandsFemaleEpigeneticsMedical GeneticsGenome-Wide Association Study
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EPDR1 up-regulation in human colorectal cancer is related to staging and favours cell proliferation and invasiveness

2020

The finding of novel molecular markers for prediction or prognosis of invasiveness in colorectal cancer (CRC) constitutes an appealing challenge. Here we show the up-regulation of EPDR1 in a prospective cohort of 101 CRC patients, in a cDNA array of 43 patients and in in silico analyses. EPDR1 encodes a protein related to ependymins, a family of glycoproteins involved in intercellular contacts. A thorough statistical model allowed us to conclude that the gene is significantly up-regulated in tumour tissues when compared with normal mucosa. These results agree with those obtained by the analysis of three publicly available databases. EPDR1 up-regulation correlates with the TNM staging parame…

AdultMale0301 basic medicineEpithelial-Mesenchymal TransitionColorectal cancerIn silicolcsh:MedicineNerve Tissue ProteinsBiologyArticle//purl.org/becyt/ford/3.3 [https]03 medical and health sciences0302 clinical medicinemedicinecancerHumansNeoplasm InvasivenesshumanProspective StudiesEpithelial–mesenchymal transitionlcsh:ScienceAgedCell ProliferationNeoplasm StagingcolorectalAged 80 and overRegulation of gene expressionMultidisciplinaryCell growthlcsh:RMethylationMiddle Agedmedicine.diseaseColorectal cancerNeoplasm ProteinsUp-RegulationEPDR1Gene Expression Regulation Neoplastic030104 developmental biologyCpG siteCell culture030220 oncology & carcinogenesisCancer research//purl.org/becyt/ford/3 [https]Femalelcsh:QColorectal NeoplasmsTranscriptionScientific Reports
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Associations of LPL and APOC3 gene polymorphisms on plasma lipids in a mediterranean population: Interaction with tobacco smoking and the APOE locus

2002

We conducted a cross-sectional study in a Spanish population (n = 1,029) to investigate associations between the LPL and APOC3 gene loci (LPL-HindIII, LPL-S447X, and APOC3-SstI) and plasma lipid levels and their interaction with APOE polymorphisms and smoking. Carriers of the H− or the X447 allele had higher levels of HDL cholesterol (HDL-C), and lower levels of TG, after adjustment for age, body mass index, alcohol, smoking, exercise, and education (P < 0.01). The APOC3 polymorphism presented additive effects to the LPL variants on TG and HDL-C levels in men, and on TG in women. The most and the least favorable haplotype combinations were H−/X447/S1 and H+/S447/S2, respectively. These comb…

AdultMaleApolipoprotein Emedicine.medical_specialtyapolipoprotein C-IIIPopulationlipoprotein lipaseLocus (genetics)Deoxyribonuclease HindIIIQD415-436Biochemistrylipidschemistry.chemical_compoundApolipoproteins EEndocrinologyInternal medicineHumansMedicineAlleleApolipoproteins CDeoxyribonucleases Type II Site-SpecificeducationTriglyceridesGeneticseducation.field_of_studyLipoprotein lipasePolymorphism Geneticbusiness.industryCholesterolCholesterol HDLSmokingHaplotypeGenetic Variationnutritional and metabolic diseasesCell BiologyCross-Sectional StudiesEndocrinologychemistrySpainFemalelipids (amino acids peptides and proteins)gene-environmental interactionbusinessBody mass index
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Risk of surgical site infections following hip and knee arthroplasty: Results of the ischia-gisio study

2017

Surgical Site Infection (SSI) is one of the major complications following insertion of hip or knee prosthesis. The aim of the present study was to describe rates of SSIs and associated risk factors during hip and knee prosthesis procedures in Italian hospitals. METHODS: Italian hospitals were invited to join the ISChIA (Surgical Site Infections in Arthroplasty Surgery) project and participated in the study on a voluntary basis. SSI surveillance was performed according to the Hospitals in Europe Link for Infection Control through Surveillance (HELICS) -SSI protocol. The study population consisted of all patients who had a prosthetic knee or hip joint replacement between March 2010 and Februa…

AdultMaleArthroplasty Replacement HipOperative TimeSettore MED/42 - Igiene Generale E ApplicataYoung AdultRisk FactorsSettore MED/33 - Malattie Apparato LocomotoreHumansSurgical Wound InfectionProspective StudiesArthroplasty Replacement KneeAgedAged 80 and overInfection Risk Index Operation length Surgical site infection SurveillanceSurveillanceIncidenceEnvironmental and Occupational HealthInfection Risk IndexMiddle AgedOperation lengthinfection risk index; operation length; surgical site infection; surveillance; public health environmental and occupational health; infectious diseasesInfectious DiseasesItalyPopulation SurveillanceMultivariate AnalysisFemalePublic HealthSurgical site infection
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Extent and patterns of MGMT promoter methylation in glioblastoma- and respective glioblastoma-derived spheres.

2010

Abstract Purpose: Quantitative methylation-specific tests suggest that not all cells in a glioblastoma with detectable promoter methylation of the O6-methylguanine DNA methyltransferase (MGMT) gene carry a methylated MGMT allele. This observation may indicate cell subpopulations with distinct MGMT status, raising the question of the clinically relevant cutoff of MGMT methylation therapy. Epigenetic silencing of the MGMT gene by promoter methylation blunts repair of O6-methyl guanine and has been shown to be a predictive factor for benefit from alkylating agent therapy in glioblastoma. Experimental Design: Ten paired samples of glioblastoma and respective glioblastoma-derived spheres (GS), c…

AdultMaleCancer ResearchMethyltransferaseDNA repairBiologyDNA methyltransferaseGene dosageO(6)-Methylguanine-DNA MethyltransferaseGene FrequencyTumor Cells CulturedHumansPromoter Regions GeneticneoplasmsAgedAged 80 and overBrain NeoplasmsO-6-methylguanine-DNA methyltransferaseMethylationDNA MethylationMiddle AgedMolecular biologydigestive system diseasesChromatinOncologyCpG siteDNA methylationFemaleGlioblastomaClinical cancer research : an official journal of the American Association for Cancer Research
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Genome-Wide Association Studies of the PR Interval in African Americans.

2011

The PR interval on the electrocardiogram reflects atrial and atrioventricular nodal conduction time. The PR interval is heritable, provides important information about arrhythmia risk, and has been suggested to differ among human races. Genome-wide association (GWA) studies have identified common genetic determinants of the PR interval in individuals of European and Asian ancestry, but there is a general paucity of GWA studies in individuals of African ancestry. We performed GWA studies in African American individuals from four cohorts (n = 6,247) to identify genetic variants associated with PR interval duration. Genotyping was performed using the Affymetrix 6.0 microarray. Imputation was p…

AdultMaleCancer ResearchMuscle ProteinsSingle-nucleotide polymorphismGenome-wide association studyQH426-470030204 cardiovascular system & hematologyBiologyGenetics and Genomics/Complex TraitsPolymorphism Single NucleotideSodium ChannelsWhite PeopleNAV1.5 Voltage-Gated Sodium ChannelNAV1.8 Voltage-Gated Sodium Channel03 medical and health sciencesElectrocardiography0302 clinical medicineAsian PeopleCardiovascular Disorders/Arrhythmias Electrophysiology and PacingGeneticsSNPHumansCardiac and Cardiovascular SystemsPR intervalInternational HapMap ProjectMyeloid Ecotropic Viral Integration Site 1 ProteinMolecular BiologyGenotypingGenetics (clinical)Ecology Evolution Behavior and Systematics030304 developmental biologyAgedGeneticsHomeodomain Proteins0303 health sciencesArrhythmias CardiacHeart-rate;Atherosclerosis risk; Genetic-analysis; Common variants; Design; Populations; Objectives; Conduction; Disease; TwinsMiddle AgedNeoplasm ProteinsMinor allele frequencyBlack or African AmericanAtrioventricular NodeFemaleT-Box Domain ProteinsImputation (genetics)Research ArticleGenome-Wide Association Study
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Primary cutaneous melanoma in hidden sites is associated with thicker tumours — a study of 829 patients

2001

The aim of this study was to determine if primary cutaneous melanomas in hidden anatomical sites were associated with thicker tumours. Retrospective medical data of 829 patients with melanomas diagnosed at our centre between January 1976 and July 1998 were recorded from our database. Three groups were defined according to the anatomical site of the primary melanoma: (1) visible areas (group 1: 493 patients); (2) visible areas only to the patients or to their partners in privacy (group 2: 281 patients); and (3) hidden areas (group 3: 55 patients). Univariate analysis indicated that patients with melanoma in hidden regions presented significantly thicker tumours (median for group 3: 2.25 vers…

AdultMaleCancer Researchmedicine.medical_specialtySkin NeoplasmsMultivariate analysisAdolescentDiseaseBreslow ThicknessSex FactorsInternal medicinemedicineHumansMelanomaAgedNeoplasm StagingRetrospective StudiesAged 80 and overAnalysis of VarianceUnivariate analysisbusiness.industryMelanomaAge FactorsRetrospective cohort studyMiddle Agedmedicine.diseaseSurgeryAnatomical sitesOncologyCutaneous melanomaFemalebusinessEuropean Journal of Cancer
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