Search results for " Basic"

showing 10 items of 10515 documents

Homozygous Familial Hypercholesterolemia in Spain Prevalence and Phenotype-Genotype Relationship

2016

Background— Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor ( LDLR ), apolipoprotein B ( APOB ), proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), and LDL protein receptor adaptor 1 ( LDLRAP1 ). No epidemiological studies have assessed HoFH prevalence or the clinical and molecular characteristics of this condition. Here, we aimed to characterize HoFH in Spain. Methods and Results— Data were collected from the Spanish Dyslipidemia Regist…

Male0301 basic medicineOncologyLdl receptor geneApolipoprotein BLipid-lowering therapyFamilial hypercholesterolemia030204 cardiovascular system & hematologyCompound heterozygosity0302 clinical medicineAutosomal-dominant hypercholesterolemiaRisk FactorsEpidemiologyPrevalenceDiseaseRegistriesGenetics (clinical)Molecular EpidemiologybiologyhypercholesterolemiaHomozygoteDouble-blindMiddle AgedPhenotypeCardiovascular DiseasesApolipoprotein B-100allelesFemalelipids (amino acids peptides and proteins)Proprotein Convertase 9Cardiology and Cardiovascular MedicineMutationsAdultGenetic MarkersHeterozygotemedicine.medical_specialtyInhibitorAdolescentPlacebo-controlled trialHyperlipoproteinemia Type IIlipidsYoung Adult03 medical and health sciencesInternal medicineGeneticsmedicineHumansGenetic Predisposition to DiseaseAlleleAdaptor Proteins Signal TransducingRecessive hypercholesterolemiaPCSK9registriesCholesterol LDLApolipoprotein-bmedicine.disease030104 developmental biologyEndocrinologyReceptors LDLSpainMutationLDL receptorbiology.proteinmutationDyslipidemia
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A Phase Ib Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Cobimetinib and Duligotuzumab in Patients with Previously Treat…

2017

Abstract Lessons Learned Cobimetinib and duligotuzumab were well tolerated as single agents and in combination with other agents. The cobimetinib and duligotuzumab combination was associated with increased toxicity, most notably gastrointestinal, and limited efficacy in the patient population tested. Background KRAS-mutant tumors possess abnormal mitogen-activated protein kinases (MAPK) pathway signaling, leading to dysregulated cell proliferation. Cobimetinib blocks MAPK signaling. The dual-action antibody duligotuzumab (MEHD7945A) inhibits ligand binding to both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3). Blockade of EGFR/HER3 and inhibitio…

Male0301 basic medicineOncologyMAPK/ERK pathwayCancer ResearchReceptor ErbB-3MAP Kinase Kinase 1Administration Oralmedicine.disease_causechemistry.chemical_compound0302 clinical medicinePiperidinesAntineoplastic Combined Chemotherapy ProtocolsMedicineProspective StudiesEpidermal growth factor receptor31biologyMiddle AgedErbB ReceptorsTreatment OutcomeOncologyTolerability030220 oncology & carcinogenesisFemaleDrug EruptionsKRASmedicine.symptomColorectal NeoplasmsSignal TransductionAdultmedicine.medical_specialty4HypokalemiaAcneiform eruptionProto-Oncogene Proteins p21(ras)03 medical and health sciencesAcneiform EruptionsInternal medicineHumansAdverse effectAgedNeoplasm StagingCobimetinibDose-Response Relationship Drugbusiness.industryClinical Trial Resultsmedicine.disease030104 developmental biologychemistryAstheniaImmunoglobulin Gbiology.proteinAzetidinesbusinessProgressive diseaseThe Oncologist
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Genetic systems for a new approach to risk of progression of diabetic retinopathy.

2016

OBJECTIVE: To evaluate the risk of progression of diabetic retinopathy (DR) using new strategies to obtain genetic information in type 2 diabetes (T2D) based on interfering ribonucleic acid (RNA). MATERIAL AND METHODS: A prospective multicentre case-control study of 132 participants was distributed into: T2D with (+DR) or without (-DR) (T2DG; n=77), and a control group (CG; n=55). After an eye examination and personal interview, tears were collected for molecular analysis (expression of microRNAs [miRNAs] (miRCURY ARN Isolation Kit, Qiagen)]. Libraries, 137 vs. 140bp (GeneMapper, Applied Biosystems), were obtained in 18 samples (T2DG+DR=6; T2DG-DR=6; CG=6) by performing next-generation sequ…

Male0301 basic medicineOncologyMicro RNAsmedicine.medical_specialtyBiomarcadores preclinicosType 2 diabetesMicro-ARNBioinformaticsRisk AssessmentInterference by RNA03 medical and health sciencesDiabetic retinopathyInternal medicineType 2 diabetes mellitusmedicineHumansProspective StudiesFamily historyAgedDiabetic Retinopathymedicine.diagnostic_testSequence Analysis RNAbusiness.industryPre-clinical biomarkersType 2 Diabetes MellitusGenetic systemsRetinopatia diabeticaGeneral MedicineDiabetic retinopathyMiddle Agedmedicine.diseaseInterferencia por ARNMolecular analysisDiabetes mellitus tipo 2030104 developmental biologyDiabetes Mellitus Type 2Eye examinationCase-Control StudiesDisease ProgressionTearsFemalebusinessBiomarcadores preclínicos Diabetes mellitus tipo 2 Diabetic retinopathy Interference by RNA Interferencia por ARN Micro RNAs Micro-ARN Pre-clinical biomarkers Retinopatía diabética Type 2 diabetes mellitus
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Non-targeted metabolomic biomarkers and metabotypes of type 2 diabetes: A cross-sectional study of PREDIMED trial participants

2019

Aim. - To characterize the urinary metabolomic fingerprint and multi-metabolite signature associated with type 2 diabetes (T2D), and to classify the population into metabotypes related to T2D. Methods. - A metabolomics analysis using the 1 H-NMR-based, non-targeted metabolomic approach was conducted to determine the urinary metabolomic fingerprint of T2D compared with non-T2D participants in the PREDIMED trial. The discriminant metabolite fingerprint was subjected to logistic regression analysis and ROC analyses to establish and to assess the multi-metabolite signature of T2D prevalence, respectively. Metabotypes associated with T2D were identified using the k-means algorithm. Results. - A …

Male0301 basic medicineOncologyNon targetedendocrine system diseasesCross-sectional studyEndocrinology Diabetes and MetabolismType 2 diabetesDiet MediterraneanLogistic regressionDiabetis no-insulinodependentEndocrinologyRisk FactorsNon-insulin-dependent diabetesDietoteràpiaeducation.field_of_studyFactors de risc en les malaltiesBiochemical markersGeneral MedicineMiddle AgedMetabolismeMetabolòmicaCardiovascular DiseasesMarcadors bioquímicsMetabolomeFemalemedicine.medical_specialtyRisk factors in diseasesPopulationUrinalysis03 medical and health sciencesMedicina preventivaMetabolomicsInternal medicineInternal MedicinemedicineHumansMetabolomicseducationAgedPreventive medicineReceiver operating characteristicbusiness.industryDiet therapynutritional and metabolic diseasesmedicine.diseasePredimedMetabolismCross-Sectional Studies030104 developmental biologyDiabetes Mellitus Type 2businesshuman activitiesBiomarkersDiabetic AngiopathiesDiabetes & Metabolism
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Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium

2016

Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10−6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up. Res…

Male0301 basic medicineOncologyPREDICTIONMyocardial Infarctionlcsh:MedicineGenome-wide association studyCoronary Artery DiseaseCardiovascular MedicineSUSCEPTIBILITY030204 cardiovascular system & hematologyCardiovascularBioinformaticsincident myocardial infarctionCohort StudiesCoronary artery diseaseMathematical and Statistical Techniques0302 clinical medicineDESIGNMedicine and Health Sciences2.1 Biological and endogenous factorsProspective StudiesMyocardial infarctionAetiologyCooperative Behaviorlcsh:ScienceProspective cohort studyRISKscreening and diagnosisMultidisciplinaryResearch Support Non-U.S. Gov'tSingle NucleotideGenomicsMiddle Aged3. Good healthMultidisciplinary SciencesDetectionCHROMOSOME 9P21Heart DiseaseResearch DesignCardiovascular DiseasesCARDIOVASCULAR-DISEASEPhysical SciencesScience & Technology - Other TopicsFemaleStatistics (Mathematics)4.2 Evaluation of markers and technologiesResearch ArticleCohort studymedicine.medical_specialtyGeneral Science & TechnologyCardiologySingle-nucleotide polymorphismResearch and Analysis MethodsGenome ComplexityPolymorphism Single Nucleotide03 medical and health sciencescoronary hearth diseaseInternal medicineMD MultidisciplinaryGenome-Wide Association StudiesGeneticsJournal ArticlemedicineHumansSNPGenetic Predisposition to DiseasePolymorphismStatistical MethodsHeart Disease - Coronary Heart DiseaseMETAANALYSISAgedGenetic associationta112Science & Technologybusiness.industryPreventionlcsh:RHuman GenomeBiology and Life SciencesComputational BiologyHuman GeneticsGenome AnalysisROTTERDAMmedicine.diseaseIntronsGood Health and Well Being030104 developmental biologyGenetic LociGenetics of Diseaselcsh:Q3111 BiomedicinebusinessMathematicsMeta-AnalysisGenome-Wide Association StudyPLOS ONE
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Palbociclib plus endocrine therapy in HER2 negative, hormonal receptor-positive, advanced breast cancer: A real-world experience

2019

Data from 423 human epidermal growth factor receptor 2-negative (HER2−), hormone receptor-positive (HR+) advanced breast cancer (aBC) patients treated with palbociclib and endocrine therapy (ET) were provided by 35 Italian cancer centers and analyzed for treatment outcomes. Overall, 158 patients were treated in first line and 265 in second/later lines. We observed 19 complete responses and 112 partial responses. The overall response rate (ORR) was 31% (95% confidence interval [CI], 26.6–35.4) and clinical benefit was 52.7% (95% CI, 48–57.5). ORR was negatively affected by prior exposure to everolimus/exemestane (p = 0.002) and favorably influenced by early line-treatment (p < 0.0001). At…

Male0301 basic medicineOncologyPyridinesReceptor ErbB-2PhysiologyClinical BiochemistryPiperazineschemistry.chemical_compound0302 clinical medicineExemestaneAntineoplastic Combined Chemotherapy Protocolsadvanced breast cancer; hormonal therapy; endocrine resistance; palbociclib; real-world settingBreastAged 80 and overadvanced breast cancerhormonal therapyadvanced breast cancer hormonal therapy; endocrine resistance; palbociclib; real-world settingMiddle AgedTreatment OutcomeReceptors Estrogen030220 oncology & carcinogenesisToxicityFemaleReceptors Progesteronemedicine.drugAdultadvanced breast cancer hormonal therapy; endocrine resistance; palbociclib; real-world setting; Physiology; Clinical Biochemistry; Cell Biologymedicine.medical_specialtypalbociclibBreast NeoplasmsPalbociclibNeutropeniaadvanced breast cancer hormonal therapyDisease-Free Survivalendocrine resistance03 medical and health sciencesInternal medicinereal-world settingmedicineHumansAgedEverolimusSettore MED/06 - ONCOLOGIA MEDICAbusiness.industryCancerCell Biologymedicine.diseaseConfidence interval030104 developmental biologychemistryMED/06 - ONCOLOGIA MEDICAbusinessHormone
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Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multice…

2018

Summary Background Encorafenib plus binimetinib and encorafenib alone improved progression-free survival compared with vemurafenib in patients with BRAF V600 -mutant melanoma in the COLUMBUS trial. Here, we report the results of the secondary endpoint of overall survival. Methods COLUMBUS was a two-part, randomised, open-label, phase 3 study done at 162 hospitals in 28 countries. Eligible patients were aged at least 18 years with histologically confirmed, locally advanced, unresectable, or metastatic cutaneous melanoma, or unknown primary melanoma, BRAF V600E or BRAF V600K mutation, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and were treatment naive or had pr…

Male0301 basic medicineOncologySkin NeoplasmsTime FactorsMedizinPhases of clinical researchGene mutationchemistry.chemical_compound0302 clinical medicineAntineoplastic Combined Chemotherapy ProtocolsVemurafenibMelanomaAged 80 and overTrametinibSulfonamides10177 Dermatology ClinicBinimetinibMiddle AgedProgression-Free SurvivalPhenotypeOncologyTolerability030220 oncology & carcinogenesisDisease ProgressionFemale2730 Oncologymedicine.drugAdultProto-Oncogene Proteins B-rafmedicine.medical_specialty610 Medicine & healthYoung Adult03 medical and health sciencesInternal medicineBiomarkers TumormedicineHumansGenetic Predisposition to DiseaseProgression-free survivalProtein Kinase InhibitorsAgedPerformance statusbusiness.industry030104 developmental biologyVemurafenibchemistryMutationBenzimidazolesCarbamatesbusinessThe Lancet Oncology
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Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer

2018

Rossella De Luca,1 Livio Blasi,2 Massimiliano Alù,2 Valerio Gristina,1 Giuseppe Cicero1 1Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy; 2Medical Oncology Unit, ARNAS Hospital Civico, Di Cristina, Benfratelli, Palermo, Italy Purpose: Pancreatic carcinoma is the neoplasia with the major mortality, and main standard treatments in this cancer increase survival but do not lead to complete recovery of the patient. The aim of this study was to evaluate the efficacy of Abraxane® (nab-paclitaxel) in Italian patients with metastatic pancreatic cancer (MPC).Patients and methods: We conducted a retrospective …

Male0301 basic medicineOncologyTime Factorsmedicine.medical_treatmentPharmaceutical ScienceKaplan-Meier EstimatechemotherapyMetastasis0302 clinical medicineRisk FactorsDrug DiscoveryClinical endpointOriginal ResearchMiddle AgedTreatment OutcomeItalyTolerabilityCA 19-9030220 oncology & carcinogenesisFemaleCA19-9medicine.drugmedicine.medical_specialtyCA-19-9 AntigenPaclitaxeloverall survivalPainAntineoplastic AgentsAdenocarcinomaDisease-Free SurvivalAbraxane03 medical and health sciencesAlbuminsInternal medicinemedicineHumansmetastasisAbraxane chemotherapy pancreatic carcinoma metastasis CA 19-9 pain overall survivalSurvival rateAgedRetrospective StudiesPharmacologyChemotherapyDrug Design Development and Therapypancreatic carcinomabusiness.industryCancermedicine.diseaseGemcitabinePancreatic Neoplasms030104 developmental biologyLinear ModelsAlbumin-Bound PaclitaxelbusinessDrug Design, Development and Therapy
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Clinical Implications of Discordant Early Molecular Responses in CML Patients Treated with Imatinib

2019

A reduction in BCR-ABL1/ABL1IS transcript levels to &lt

Male0301 basic medicineOncologyTreatment outcomeFusion Proteins bcr-ablAntineoplastic Agentlcsh:ChemistryBcr abl10302 clinical medicinehemic and lymphatic diseasesimatinib mesylateBCR-ABL1; European Leukemia Net; chronic myeloid leukemia; early molecular response; imatinib mesylatelcsh:QH301-705.5<i>BCR-ABL1</i>SpectroscopyAged 80 and overGeneral MedicineMiddle AgedComputer Science ApplicationsTreatment Outcome030220 oncology & carcinogenesisFemaleHumanmedicine.drugAdultmedicine.medical_specialtyProtein Kinase InhibitorAntineoplastic AgentsArticleCatalysisEuropean Leukemia NetInorganic Chemistry03 medical and health scienceschronic myeloid leukemiaLeukemia Myelogenous Chronic BCR-ABL PositiveInternal medicineBiomarkers TumormedicineHumansIn patientRNA MessengerPhysical and Theoretical ChemistryProtein Kinase InhibitorsMolecular BiologyAgedbusiness.industryOrganic ChemistryImatinibBCR-ABL1030104 developmental biologyImatinib mesylatelcsh:Biology (General)lcsh:QD1-999early molecular responsebusiness
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Vinflunine in the treatment of relapsed metastatic urothelial cancer: A systematic review and meta-analysis of real-world series

2019

Background. Vinflunine (VFL) is approved in Europe as second-line treatment of metastatic urothelial cancer after failure of platinum-containing therapy. We performed a systematic review and meta-analysis of real-world data (RWD) to assess utilization, efficacy and safety of VFL. \ud \ud Methods. We performed a MEDLINE search for the period of 1/1/2000-31/8/2017. Full-length articles providing post-marketing RWD on VFL in patients failing previous chemotherapy were eligible. Interventional clinical trials were excluded. \ud \ud Results: Ten studies with 797 patients were identified. According to pooled REs analysis, overall response rate was 19%, most frequent, all-grade toxicities were fat…

Male0301 basic medicineOncologyUrologic Neoplasmsmedicine.medical_specialtyVomitingNauseamedicine.medical_treatmentMEDLINEPlatinum CompoundsNeutropeniaVinblastine03 medical and health scienceschemistry.chemical_compound0302 clinical medicineRecurrenceInternal medicineAntineoplastic Combined Chemotherapy ProtocolsHumansMedicineNeoplasm MetastasisFatigueAgedChemotherapyVinfluninebusiness.industryNauseaHematologyMiddle Agedmedicine.diseaseEuropeClinical trialTreatment Outcome030104 developmental biologyOncologychemistry030220 oncology & carcinogenesisMeta-analysisVomitingFemalemedicine.symptombusinessConstipationCritical Reviews in Oncology/Hematology
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