Search results for "clinical research"

showing 10 items of 474 documents

Threshold Effects of Circulating Angiopoietin-Like 3 Levels on Plasma Lipoproteins.

2017

Abstract Context Angiopoietin-like 3 (ANGPTL3) deficiency in plasma due to loss-of-function gene mutations results in familial combined hypobetalipoproteinemia type 2 (FHBL2) in homozygotes. However, the lipid phenotype in heterozygotes is much milder and does not appear to relate directly to ANGPTL3 levels. Furthermore, the low-density lipoprotein (LDL) phenotype in carriers of ANGPTL3 mutations is unexplained. Objective To determine whether reduction below a critical threshold in plasma ANGPTL3 levels is a determinant of lipoprotein metabolism in FHBL2, and to determine whether proprotein convertase subtilisin kexin type 9 (PCSK9) is involved in determining low LDL levels in this conditio…

0301 basic medicineMaleApolipoprotein BEndocrinology Diabetes and MetabolismClinical BiochemistryBiochemistryLipoprotein particlePCSK9Cohort StudiesHypobetalipoproteinemiaschemistry.chemical_compoundEndocrinologyANGPTL3biologyChemistryMiddle AgedPedigreeLipoproteins LDLPhenotypeKexinlipids (amino acids peptides and proteins)FemaleANGPTL3; familial combined hypolipidemia; PCSK9Lipoproteins HDLAdultmedicine.medical_specialtyHeterozygoteBlotting Western03 medical and health sciencesInternal medicinemedicineHumansGenetic Predisposition to DiseaseClinical Research ArticlesAgedAngiopoietin-Like Protein 3Apolipoproteins BCholesterolPCSK9Biochemistry (medical)medicine.disease030104 developmental biologyEndocrinologyAngiopoietin-like ProteinsLDL receptorMultivariate AnalysisMutationbiology.proteinLinear Modelsfamilial combined hypobetalipoproteinemiaHypobetalipoproteinemiaAngiopoietinsLipoprotein
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Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma.

2015

Few patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) achieve prolonged disease-free survival. Blinatumomab, a bispecific T-cell engaging antibody construct, transiently links CD3-positive T cells to CD19-positive B cells. This phase 2 study evaluated stepwise (9-28-112 μg/d with weekly dose increases; n = 23) or flat (112 μg/d; n = 2) dosing of blinatumomab by continuous infusion, with dexamethasone prophylaxis, in patients with relapsed/refractory DLBCL. Patients received a median of 3 prior lines of therapy. Median time since last regimen was 1.5 months. Seventeen patients ended treatment in cycle 1 (induction), 7 in cycle 2 (consolidation), and 1 in retreatment. Am…

0301 basic medicineMaleCD3 ComplexClinical Trials and ObservationsSalvage therapyPhases of clinical researchKaplan-Meier EstimateBiochemistryGastroenterologyDexamethasone0302 clinical medicineRecurrenceAntibodies BispecificMedicineMolecular Targeted TherapyFatigueRemission InductionHematologyMiddle AgedTumor Burden030220 oncology & carcinogenesisBlinatumomabFemaleImmunotherapyLymphoma Large B-Cell Diffusemedicine.drugAdultmedicine.medical_specialtyFeverImmunologyAntigens CD19Antineoplastic AgentsDisease-Free SurvivalDrug Administration Schedule03 medical and health sciencesAntigens NeoplasmInternal medicineHumansDosingAdverse effectAgedSalvage TherapyDose-Response Relationship Drugbusiness.industryCell Biologymedicine.diseaseLymphomaSurgeryRegimen030104 developmental biologyNervous System DiseasesbusinessDiffuse large B-cell lymphomaBlood
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Phase II study of necitumumab plus modified FOLFOX6 as first-line treatment in patients with locally advanced or metastatic colorectal cancer

2016

Background:This single-arm phase II study investigated the EGFR monoclonal antibody necitumumab plus modified FOLFOX6 (mFOLFOX6) in first-line treatment of locally advanced or metastatic colorectal cancer (mCRC).Methods:Patients received 800-mg intravenous necitumumab (day 1; 2-week cycles), followed by oxaliplatin 85 mg m -2, folinic acid 400 mg m -2, and 5-fluorouracil (400 mg m -2 bolus then 2400 mg m -2 over 46 h). Radiographic evaluation was performed every 8 weeks until progression. Primary endpoint was objective response rate.Results:Forty-four patients were enrolled and treated. Objective response rate was 63.6% (95% confidence interval 47.8-77.6); complete response was observed in …

0301 basic medicineMaleCancer ResearchOrganoplatinum CompoundsLeucovorinPhases of clinical researchmedicine.disease_causeGastroenterology0302 clinical medicineadvanced colorectal cancerAntineoplastic Combined Chemotherapy ProtocolsClinical endpointNeoplasm MetastasisNecitumumabModified FOLFOX6Aged 80 and overnecitumumabAntibodies MonoclonalMiddle AgedOxaliplatinTreatment OutcomeOncologyFluorouracil030220 oncology & carcinogenesisFemaleKRASFluorouracilColorectal Neoplasmsmedicine.drugAdultmedicine.medical_specialtyEGFRNeutropeniamodified FOLFOX6Antibodies Monoclonal HumanizedDisease-Free SurvivalProto-Oncogene Proteins p21(ras)03 medical and health sciencesFolinic acidInternal medicinemedicineKRASHumansAdvanced colorectal cancerAgedbusiness.industrymedicine.diseaseSurvival AnalysisSurgeryOxaliplatinCancérologie030104 developmental biologyClinical StudybusinessNecitumumabBritish Journal of Cancer
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Transcriptome-Wide Analysis Identifies Novel Associations With Blood Pressure.

2017

Hypertension represents a major cardiovascular risk factor. The pathophysiology of increased blood pressure (BP) is not yet completely understood. Transcriptome profiling offers possibilities to uncover genetics effects on BP. Based on 2 populations including 2549 individuals, a meta-analyses of monocytic transcriptome-wide profiles were performed to identify transcripts associated with BP. Replication was performed in 2 independent studies of whole-blood transcriptome data including 1990 individuals. For identified candidate genes, a direct link between long-term changes in BP and gene expression over time and by treatment with BP-lowering therapy was assessed. The predictive value of pro…

0301 basic medicineMaleCandidate geneGene ExpressionGenome-wide association studyBlood Pressure030204 cardiovascular system & hematologyCardiorespiratory Medicine and HaematologyCardiovascularLMNATranscriptome0302 clinical medicineRisk FactorsCEBPAGene expression2.1 Biological and endogenous factorsAetiologyGeneticsMyelin and Lymphocyte-Associated Proteolipid ProteinsBlood Pressure ; Gene Expression ; Genome-wide Association Study ; Hypertension ; Transcriptomeblood pressureGenomicsSingle NucleotideLIM Domain Proteinsblood pressure; gene expression; genome-wide association study; hypertension; transcriptomeStrokeHeart DiseaseHypertensionPublic Health and Health ServicesBiomarker (medicine)FemaleEssential HypertensionPoly(ADP-ribose) PolymerasesBiotechnologyAdulthypertensionClinical SciencesNucleoside Transport ProteinsBiologyPolymorphism Single NucleotideArticle03 medical and health sciencesClinical ResearchInternal MedicineGeneticsHumansPolymorphismgenome-wide association studyGene Expression ProfilingHuman GenomeBlood Pressure DeterminationGene expression profiling030104 developmental biologyGood Health and Well BeingCardiovascular System & Hematologygene expressionCCAAT-Enhancer-Binding ProteinsCarrier ProteinstranscriptomeTranscription Factors
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Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open-label, phase 2 study.

2017

Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug-related adverse events, the other was not drug-related), …

0301 basic medicineMaleWalkingchemistry.chemical_compoundGrip strengthGALNS protein0302 clinical medicineElosulfase alfaQuality of lifeActivities of Daily LivingRespiratory functionFunctional abilityChildGenetics (clinical)education.field_of_studyMucopolysaccharidosis IVChondroitinsulfatases3. Good healthRespiratory Function TestsTreatment OutcomeTolerability6.1 PharmaceuticalsOriginal ArticleFemalePatient Safetyphysical enduranceGALNS protein human [supplementary concept]Adultsafetymedicine.medical_specialtyAdolescentClinical Trials and Supportive ActivitiesPopulationClinical Sciences03 medical and health sciencesYoung Adultmobility limitationClinical ResearchInternal medicinemedicineGeneticsHumansEnzyme Replacement TherapyAdverse effecteducationhuman [supplementary concept]Exercisebusiness.industryEvaluation of treatments and therapeutic interventionsOriginal Articles030104 developmental biologychemistryKeratan SulfateQuality of LifeSelf Reportbusiness030217 neurology & neurosurgeryBiomarkers
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Mesothelioma and thymic tumors: Treatment challenges in (outside) a network setting.

2017

The management of patients with mesothelioma and thymic malignancy requires continuous multidisciplinary expertise at any step of the disease. A dramatic improvement in our knowledge has occurred in the last few years, through the development of databases, translational research programs, and clinical trials. Access to innovative strategies represents a major challenge, as there is a lack of funding for clinical research in rare cancers and their rarity precludes the design of robust clinical trials that could lead to specific approval of drugs. In this context, patient-centered initiatives, such as the establishment of dedicated networks, are warranted. International societies, such as IMI…

0301 basic medicineMesotheliomamedicine.medical_specialtyInternational CooperationPleural NeoplasmsMEDLINESocio-culturaleContext (language use)Translational researchDiseaseSocial Networking03 medical and health sciences0302 clinical medicineMultidisciplinary approachMedicineHumansMesotheliomaPleural NeoplasmIntensive care medicinebusiness.industryGeneral MedicineThymus Neoplasmsmedicine.diseaseClinical trialEuropeSurvival Rate030104 developmental biologyClinical researchOncology030220 oncology & carcinogenesisSurgery; OncologySurgerybusinessDelivery of Health Caremesothelioma thymic tumours clinical trialsHumanEuropean journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
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Microbial Ecology on Solar Panels in Berkeley, CA, United States

2018

Solar panels can be found practically all over the world and represent a standard surface that can be colonized by microbial communities that are resistant to harsh environmental conditions, including high irradiation, temperature fluctuations and desiccation. These properties make them not only ideal sources of stress-resistant bacteria, but also standard devices to study the microbial communities and their colonization process from different areas of Earth. We report here a comprehensive description of the microbial communities associated with solar panels in Berkeley, CA, United States. Cultivable bacteria were isolated to characterize their adhesive capabilities, and UV- and desiccation…

0301 basic medicineMicrobiology (medical)FirmicutesEnvironmental Science and Management030106 microbiologylcsh:QR1-502microbiomeMicrobiologylcsh:MicrobiologyActinobacteria03 medical and health sciencesMetabolomicsMicrobial ecologyClinical ResearchBotanyMetabolomeMetabolomicsStress-resistant bacteriasolar panelsOriginal ResearchmetagenomicsSolar panelsbiologyBacteroidetesbiology.organism_classificationmetabolomicsInfectious Diseasesstress-resistant bacteriaMetagenomicsSoil SciencesMicrobiomeMetagenomicsProteobacteriaFrontiers in Microbiology
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How to Deal with Second Line Dilemma in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis

2019

Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy with chemotherapy (CT) as second line treatment for metastatic colorectal cancer (mCRC). The right sequence of the treatments in all RAS (KRAS/NRAS) wild type (wt) patients has not precisely defined. We evaluated the impact of aforementioned targeted therapies in second line setting, analyzing efficacy and safety data from phase III clinical trials. We performed both direct and indirect comparisons between anti-EGFR and anti-VEGF. Outcomes included disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall su…

0301 basic medicineNeuroblastoma RAS viral oncogene homologOncologyCancer Researchmedicine.medical_specialtytargeted agentsColorectal cancermedicine.medical_treatmentEGFRPopulationPhases of clinical researchcolorectal cancerReviewmedicine.disease_causelcsh:RC254-282meta-analysi03 medical and health sciences0302 clinical medicineInternal medicinemedicineEpidermal growth factor receptoreducationChemotherapyeducation.field_of_studybiologybusiness.industrysequencemedicine.diseaselcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogensVEGFmeta-analysis030104 developmental biologyOncology030220 oncology & carcinogenesisMeta-analysisbiology.proteinKRASsecond linebusinessCancers
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Efficacy of Sequential Ipilimumab Monotherapy versus Best Supportive Care for Unresectable Locally Advanced/Metastatic Gastric or Gastroesophageal Ju…

2017

Abstract Purpose: Ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte–associated protein-4 interactions, enhances T-cell activation and promotes tumor immunity. This phase II study evaluated the safety and efficacy of ipilimumab monotherapy versus best supportive care (BSC) among patients with advanced/metastatic gastric or gastroesophageal junction cancer who achieved at least stable disease with first-line chemotherapy. Experimental Design: Eligible patients were randomized to ipilimumab 10 mg/kg every 3 weeks for four doses, then 10 mg/kg every 12 weeks for up to 3 years, or BSC, which could include continuation of fluoropyrimidine until progression or toxicity. The prim…

0301 basic medicineOncologyAdultMaleCancer Researchmedicine.medical_specialtyDrug-Related Side Effects and Adverse ReactionsEsophageal NeoplasmsPhases of clinical researchIpilimumabDisease-Free Survivallaw.invention03 medical and health sciences0302 clinical medicineRandomized controlled triallawStomach NeoplasmsInternal medicineAntineoplastic Combined Chemotherapy ProtocolsmedicineClinical endpointHumansAdverse effectAgedbusiness.industryCancerMiddle AgedInterim analysismedicine.diseaseIpilimumabSurgeryClinical trial030104 developmental biologyOncology030220 oncology & carcinogenesisFemaleEsophagogastric Junctionbusinessmedicine.drugClinical cancer research : an official journal of the American Association for Cancer Research
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Final results of the McCAVE trial: A double-blind, randomized phase 2 study of vanucizumab (VAN) plus FOLFOX vs. bevacizumab (BEV) plus FOLFOX in pat…

2017

3539 Background: VEGF-A and ANG-2 have complementary roles in regulation of tumor angiogenesis. Targeting VEGF-A with BEV in combination chemotherapy (CT) in mCRC has proven to increase PFS and OS. ANG-2 is overexpressed and associated with poor outcome of mCRC pts receiving BEVcontaining treatment. Hence, dual blockade of VEGF-A and ANG-2 by the bispecific mAb VAN with standard CT may improve clinical activity in mCRC. Methods: All pts received mFOLFOX-6 and were randomized 1:1 to also receive intravenous VAN 2000 mg every other week (Q2W) (Arm A) or BEV 5 mg/kg Q2W (Arm B). The primary end point was investigator assessed progression-free survival (PFS). Key eligibility criteria included …

0301 basic medicineOncologyCancer Researchmedicine.medical_specialtyBevacizumabColorectal cancerbusiness.industryPhases of clinical researchCombination chemotherapymedicine.diseaseSurgeryDouble blind03 medical and health sciences030104 developmental biologyOncologyFOLFOXVanucizumabInternal medicinemedicineIn patientbusinessmedicine.drugJournal of Clinical Oncology
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