Search results for "Agent"

showing 10 items of 8904 documents

Imatinib spares cKit-expressing prostate neuroendocrine tumors, whereas kills seminal vesicle epithelial-stromal tumors by targeting PDGFR-β

2017

Abstract Prostate cancer is a leading cause of cancer-related death in males worldwide. Indeed, advanced and metastatic disease characterized by androgen resistance and often associated with neuroendocrine (NE) differentiation remains incurable. Using the spontaneous prostate cancer TRAMP model, we have shown that mast cells (MCs) support in vivo the growth of prostate adenocarcinoma, whereas their genetic or pharmacologic targeting favors prostate NE cancer arousal. Aiming at simultaneously targeting prostate NE tumor cells and MCs, both expressing the cKit tyrosine kinase receptor, we have tested the therapeutic effect of imatinib in TRAMP mice. Imatinib-treated TRAMP mice experience a pa…

0301 basic medicineMaleCancer ResearchReceptor tyrosine kinaseAntineoplastic AgentProstate cancerMice0302 clinical medicineProstatebiologySeminal VesiclesImmunohistochemistryGene Expression Regulation NeoplasticNeuroendocrine TumorsProto-Oncogene Proteins c-kitmedicine.anatomical_structureOncology030220 oncology & carcinogenesisImatinib MesylateFemaleNeuroendocrine Tumormedicine.drugTrampHumanSignal TransductionPCA3medicine.medical_specialtyStromal cellXenograft Model Antitumor AssayProtein Kinase InhibitorAntineoplastic AgentsMice TransgenicReceptor Platelet-Derived Growth Factor beta03 medical and health sciencesInternal medicineSeminal VesiclemedicineAnimalsHumansProtein Kinase InhibitorsAnimalProstatic NeoplasmsImatinibBiomarkermedicine.diseaseXenograft Model Antitumor AssaysDisease Models Animal030104 developmental biologyEndocrinologyImatinib mesylateProstatic Neoplasmbiology.proteinCancer researchBiomarkers
researchProduct

A phase I dose-escalation study of IMAB362 (Zolbetuximab) in patients with advanced gastric and gastro-oesophageal junction cancer

2018

Introduction IMAB362 (Zolbetuximab) is a chimeric monoclonal antibody that binds to Claudin-18.2, a target antigen specific to cancer cells. In vitro, IMAB362 mediates cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity; thus, IMAB362 may serve as a potent, targeted immunotherapeutic agent. Methods This first-in-human phase I study enroled adult patients (N = 15) with advanced gastric or gastro-oesophageal junction cancer into five sequential single dose-escalation cohorts (33, 100, 300, 600, and 1000 mg/m2) following a 3 + 3 design. Safety/tolerability, including determination of maximum tolerated dose and recommended phase II dose, were the pr…

0301 basic medicineMaleCancer Researchmedicine.medical_specialtyTime FactorsEsophageal NeoplasmsMaximum Tolerated Dosemedicine.medical_treatmentMedizinGastroenterologyAntibodies Monoclonal/administration & dosage03 medical and health sciences0302 clinical medicineAntineoplastic Agents ImmunologicalPharmacokineticsAntineoplastic Agents Immunological/administration & dosageStomach NeoplasmsInternal medicineGermanymedicineHumansDrug Dosage CalculationsAdverse effectInfusions IntravenousAgedbusiness.industryCancerAntibodies MonoclonalEsophagogastric Junction/drug effectsImmunotherapyMiddle Agedmedicine.diseaseLatviaddc:030104 developmental biologyTreatment OutcomeOncologyTolerabilityResponse Evaluation Criteria in Solid Tumors030220 oncology & carcinogenesisToxicityDisease ProgressionFemaleStomach Neoplasms/drug therapyEsophagogastric JunctionEsophageal Neoplasms/drug therapybusinessProgressive disease
researchProduct

LXR agonist treatment of blastic plasmacytoid dendritic cell neoplasm restores cholesterol efflux and triggers apoptosis

2016

International audience; Blastic plasmacytoid dendritic cell (PDC) neoplasm (BPDCN) is an aggressive hematological malignancy with a poor prognosis that derives from PDCs. No consensus for optimal treatment modalities is available today and the full characterization of this leukemia is still emerging. We identified here a BPDCN-specific transcriptomic profile when compared with those of acute myeloid leukemia and T-acute lymphoblastic leukemia, as well as the transcriptomic signature of primary PDCs. This BPDCN gene signature identified a dysregulation of genes involved in cholesterol homeostasis, some of them being liver X receptor (LXR) target genes. LXR agonist treatment of primary BPDCN …

0301 basic medicineMaleCellProliferationApoptosisExpressionPlasmacytoid dendritic cellPrecursor T-Cell Lymphoblastic Leukemia-LymphomaBiochemistryMice0302 clinical medicinepolycyclic compoundsSTAT5 Transcription Factor[ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/HematologyATP Binding Cassette Transporter Subfamily G Member 1Liver X ReceptorsInhibitionMyeloid NeoplasiabiologyMyeloid leukemiafood and beveragesMyeloid-Leukemia[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/HematologyHematologyInterleukin-3 Receptor3. Good healthLeukemiamedicine.anatomical_structureCholesterol030220 oncology & carcinogenesisFemalelipids (amino acids peptides and proteins)In-VivoATP Binding Cassette Transporter 1ImmunologyActivationAntineoplastic Agentsdigestive system03 medical and health sciencesCell Line TumormedicineAnimalsHumansLiver X receptorProtein kinase BCell ProliferationCell growthCell BiologyDendritic Cellsmedicine.diseaseXenograft Model Antitumor Assays030104 developmental biologyProstate-Cancer CellsABCA1biology.proteinCancer researchDensity-Lipoprotein ReceptorInterleukin-3Proto-Oncogene Proteins c-akt
researchProduct

Mouse tissue distribution and persistence of the food-born fusariotoxins Enniatin B and Beauvericin

2016

The fusariotoxins Enniatin B (Enn B) and Beauvericin (Bea) have recently aroused interest as food contaminants and as potential anticancer drugs. However, limited data are available about their toxic profile. Aim of this study was to investigate their pharmacological behavior in vivo and their persistence in mice. Therefore, liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to analyze the distribution of Enn B and Bea in selected tissue samples and biological fluids originating from mice treated intraperitoneally with these cyclohexadepsipeptides. Overall, no toxicological signs during life time or pathological changes were observed. Moreover, both fusariotoxins were found …

0301 basic medicineMaleColonBiological AvailabilityAntineoplastic AgentsUrinePharmacologyToxicologyTandem mass spectrometryArticlePersistence (computer science)03 medical and health scienceschemistry.chemical_compoundMice0404 agricultural biotechnologyLiquid chromatography–mass spectrometryIn vivoTandem Mass SpectrometryDepsipeptidesAnimalsTissue DistributionDepsipeptide04 agricultural and veterinary sciencesGeneral MedicineMetabolism040401 food scienceBeauvericinT-2 Toxin030104 developmental biologychemistryLiverChromatography Liquid
researchProduct

Positioning of darunavir/cobicistat-containing antiretroviral regimens in real life: results from a large multicentre observational prospective cohor…

2019

Abstract Background Study aim was to evaluate the safety and durability of darunavir/cobicistat (DRV/c) in a real life setting. Methods Multicentre prospective cohort study performed in the context of SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals). Patients were evaluated at baseline, week 24 and 48. Changes were evaluated using the paired t test or signed rank test. The multivariable analysis was performed using a general linear model, after ranking of not normally distributed variables. Results A total of 249 patients were included, 72 (29%) were in DRV/c-based dual therapies (DT). Hypercholesterolemia, HC, (total cholesterol (TC) ≥ 200 mg/dL or low density-C (LDL-C) ≥ 13…

0301 basic medicineMaleHIV Infections0302 clinical medicineDualMedicineHIV InfectionPharmacology (medical)030212 general & internal medicineProspective StudiesProspective cohort studyDarunavirCobicistatMiddle AgedViral LoadTolerabilityTolerabilityAnti-Retroviral AgentsCohortMolecular MedicineDrug Therapy CombinationFemaleDarunavir/cobicistatHumanmedicine.drugAdverse eventAdultlcsh:Immunologic diseases. Allergymedicine.medical_specialty030106 microbiologyContext (language use)Durability03 medical and health sciencesDarunavir/cobicistat Dual Durability Tolerability CISAI Adverse eventsVirologyInternal medicineHumansDarunavirbusiness.industryResearchHypertriglyceridemiamedicine.diseaseCISAIDiscontinuationProspective StudieAdverse eventsHIV-1Anti-Retroviral AgentCobicistatbusinesslcsh:RC581-607
researchProduct

Efficacy and tolerability of switching to a dual therapy with darunavir/ritonavir plus raltegravir in HIV-infected patients with HIV-1 RNA ≤50 cp/…

2017

Background: Nucleos(t)ide reverse transcriptase inhibitors (NRTI) toxicity may represent a threat for long-term success of combined antiretroviral therapy. Some studies have suggested a possible improvement of NRTI-related toxicity after switching to NRTI-sparing regimens. Objectives: We aimed to explore the efficacy and tolerability of switching to darunavir/ritonavir (DRV/r) plus raltegravir (RAL) while having a viral load (VL) ≤50 copies/mL in the clinical setting. Study design: Treatment-experienced HIV 1-infected patients enrolled in the ICONA Foundation Study cohort were included if they switched their current regimen to DRV/r + RAL with a HIV-RNA ≤50 copies/mL. Different defin…

0301 basic medicineMaleHIV InfectionsAntiretroviral therapy; Darunavir/ritonavir; Efficacy; NRTI-sparing regimen; Raltegravir; Tolerability; Microbiology (medical); Infectious DiseasesAntiretroviral therapy; Darunavir/ritonavir; Efficacy; NRTI-sparing regimen; Raltegravir; Tolerability; Adult; Anti-HIV Agents; Cohort Studies; Darunavir; Drug Therapy Combination; Female; HIV Infections; HIV-1; Humans; Italy; Male; Middle Aged; RNA Viral; Raltegravir Potassium; Ritonavir; Viral LoadGastroenterologyCohort StudiesAntiretroviral therapy; Darunavir/ritonavir; Efficacy; NRTI-sparing regimen; Raltegravir; Tolerability0302 clinical medicineMedicineNRTI-sparing regimen030212 general & internal medicineViralDarunavireducation.field_of_studyLamivudineGeneral MedicineMiddle AgedViral LoadTolerabilityAntiretroviral therapyInfectious DiseasesTolerabilityItalyCombinationRNA ViralDrug Therapy CombinationFemaleViral loadmedicine.drugAdultMicrobiology (medical)medicine.medical_specialtyEfficacyAnti-HIV Agents030106 microbiologyPopulationDarunavir/ritonavir; Raltegravir; Efficacy; Tolerability; Antiretroviral therapy; NRTI-sparing regimenSettore MED/17 - MALATTIE INFETTIVELower riskNO03 medical and health sciencesDrug TherapyInternal medicineRaltegravir PotassiumHumanseducationDarunavirRitonavirbusiness.industryDarunavir/ritonavirRaltegravirRaltegravirHIV-1RNARitonavirbusinessAntiretroviral therapy; Darunavir/ritonavir; Efficacy; NRTI-sparing regimen; Raltegravir; Tolerability;
researchProduct

Inflammasome activation in Ankylosing Spondylitis is associated to gut dysbiosis

2021

Objective: We undertook this study to evaluate the activation and functional relevance of inflammasome pathways in ankylosing spondylitis (AS) patients and rodent models and their relationship to dysbiosis. Methods: An inflammasome pathway was evaluated in the gut and peripheral blood from 40 AS patients using quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), flow cytometry, and confocal microscopy, and was compared to that of 20 healthy controls and 10 patients with Crohn’s disease. Bacteria was visualized using silver stain in human samples, and antibiotics were administered to HLA–B27–transgenic rats. The NLRP3 inhibitor MCC950 was admini…

0301 basic medicineMaleInflammasomesmedicine.medical_treatmentInterleukin-1betaInterleukin-23Mice0302 clinical medicineCrohn DiseaseNLRC4Interleukin 23Immunology and AllergyIleitisHLA-B27 AntigenSulfonamidesReverse Transcriptase Polymerase Chain ReactionCaspase 1Interleukin-17Interleukin-18InflammasomeIleitisMiddle AgedImmunohistochemistryAnti-Bacterial AgentsDNA-Binding ProteinsCytokineIndenesFemaleInterleukin 17Rats Transgenicmedicine.drugAdultAdolescentImmunologyReceptors Cell Surface03 medical and health sciencesAIM2Young AdultRheumatologyIleumNLR Family Pyrin Domain-Containing 3 ProteinmedicineAnimalsHumansSpondylitis AnkylosingFurans030203 arthritis & rheumatologybusiness.industryCalcium-Binding Proteinsmedicine.diseaseGastrointestinal MicrobiomeRatsCARD Signaling Adaptor Proteins030104 developmental biologyCase-Control StudiesImmunologyDysbiosisJointsbusinessDysbiosis
researchProduct

Incidence and risk factors for liver enzyme elevation among naive HIV-1-infected patients receiving ART in the ICONA cohort

2019

AbstractObjectivesTo evaluate the incidence and risk factors for liver enzyme elevations (LEE) in patients initiating first-line ART in the ICONA prospective observational cohort, between June 2009 and December 2017.Patients and methodsIn total, 6575 ART-naive patients were selected, initiating two NRTIs with the third drug being a boosted PI (n=2436; 37.0%), an NNRTI (n=2384; 36.3%) or an integrase strand transfer inhibitor (INSTI) (n=1755; 26.7%). HBV surface antigen and HCV RNA were detected in 3.9% and 5.8% of the study population. Inverse probability weighted Cox regression analysis was used to calculate the HRs, according to first-line regimen, for LEE, defined as ALT or AST increases…

0301 basic medicineMaleIntegrase inhibitorHepatitis B Surface AntigenHIV Infections0302 clinical medicineRisk Factorshivh epatitis c rna surface antigens follow-up homosexuality integrase inhibitors hepatitis b virus hepatitis b virus measurement hiv infections hepatotoxicity hepatitis c virus coinfection nucleoside reverse transcriptase inhibitors non-nucleoside reverse transcriptase inhibitors cox proportional hazards models baseline value liver enzyme raltegravirPharmacology (medical)HIV Infection030212 general & internal medicineProspective StudiesProspective cohort studyCoinfectionIncidence (epidemiology)Liver DiseaseIncidenceLiver Diseasesvirus diseasesHepatitis CMiddle AgedHepatitis CReverse Transcriptase InhibitorInfectious DiseasesCohortCoinfectionPopulation studyRegression AnalysisReverse Transcriptase InhibitorsFemalemedicine.drugHumanMicrobiology (medical)Adultmedicine.medical_specialtyAnti-HIV AgentsRegression AnalysiNO03 medical and health sciencesInternal medicinemedicineHumansHIV Integrase InhibitorsHIV Protease InhibitorPharmacologyHepatitis B Surface Antigensbusiness.industryAnti-HIV AgentHIV ARTHIV Protease Inhibitorsmedicine.diseaseRaltegravir030112 virologyHIV Integrase InhibitorProspective StudieHIV-1businessAdult Anti-HIV Agents Coinfection Female Hepatitis B Surface Antigens Hepatitis C HIV Infections HIV Integrase Inhibitors HIV Protease Inhibitors HIV-1 Humans Incidence Liver Diseases Male Middle Aged Prospective Studies Regression Analysis Reverse Transcriptase Inhibitors Risk Factors
researchProduct

Repurposing of the Antiepileptic Drug Levetiracetam to Restrain Neuroendocrine Prostate Cancer and Inhibit Mast Cell Support to Adenocarcinoma

2021

A relevant fraction of castration-resistant prostate cancers (CRPC) evolve into fatal neuroendocrine (NEPC) tumors in resistance to androgen deprivation and/or inhibitors of androgen receptor pathway. Therefore, effective drugs against both CRPC and NEPC are needed. We have previously described a dual role of mast cells (MCs) in prostate cancer, being capable to promote adenocarcinoma but also to restrain NEPC. This finding suggests that a molecule targeting both MCs and NEPC cells could be effective against prostate cancer. Using an in silico drug repurposing approach, here we identify the antiepileptic drug levetiracetam as a potential candidate for this purpose. We found that the protein…

0301 basic medicineMaleLevetiracetammast cellsneuroendocrine differentiationNeuroendocrine differentiationCell DegranulationAndrogen deprivation therapyProstate cancer0302 clinical medicineTumor Cells CulturedImmunology and AllergySV2AOriginal ResearchMembrane Glycoproteinsdrug repurposingCell Differentiationprostate cancerGene Expression Regulation NeoplasticMatrix Metalloproteinase 9030220 oncology & carcinogenesisAdenocarcinomaAnticonvulsantsLevetiracetammedicine.druglcsh:Immunologic diseases. AllergyImmunologyAntineoplastic AgentsMice TransgenicNerve Tissue Proteins03 medical and health sciencesmedicineAnimalsHumanstumor microenvironmentmouse modelsHigh-grade prostatic intraepithelial neoplasiadrug repurposing; mast cells; mouse models; neuroendocrine differentiation; prostate cancer; tumor microenvironmentCell Proliferationbusiness.industryDrug RepositioningProstatic NeoplasmsNeoplasms Experimentalmedicine.diseaseCarcinoma Neuroendocrinedrug repurposing mast cells mouse models neuroendocrine differentiation prostate cancer tumor microenvironmentAndrogen receptorMice Inbred C57BL030104 developmental biologyCancer researchlcsh:RC581-607business
researchProduct

Levosimendan prevents doxorubicin-induced cardiotoxicity in time- and dose-dependent manner: implications for inotropy.

2019

Abstract Aims Levosimendan (LEVO) a clinically-used inodilator, exerts multifaceted cardioprotective effects. Case-studies indicate protection against doxorubicin (DXR)-induced cardiotoxicity, but this effect remains obscure. We investigated the effect and mechanism of different regimens of levosimendan on sub-chronic and chronic doxorubicin cardiotoxicity. Methods and results Based on preliminary in vivo experiments, rats serving as a sub-chronic model of doxorubicin-cardiotoxicity and were divided into: Control (N/S-0.9%), DXR (18 mg/kg-cumulative), DXR+LEVO (LEVO, 24 μg/kg-cumulative), and DXR+LEVO (acute) (LEVO, 24 μg/kg-bolus) for 14 days. Protein kinase-B (Akt), endothelial nitric oxi…

0301 basic medicineMaleMice 129 StrainTime FactorsHeart DiseasesNitric Oxide Synthase Type IIIPhysiology030204 cardiovascular system & hematologyPharmacology03 medical and health sciences0302 clinical medicineEnosPhysiology (medical)medicineCyclic AMPCyclic GMP-Dependent Protein KinasesAnimalsDoxorubicinMyocytes CardiacCalcium SignalingRats WistarProtein kinase BCyclic GMPCells CulturedSimendanCardioprotectionMice KnockoutCardiotoxicityAntibiotics AntineoplasticbiologyDose-Response Relationship DrugChemistryCalcium-Binding ProteinsMammary Neoplasms ExperimentalCardiovascular AgentsLevosimendanbiology.organism_classificationCyclic AMP-Dependent Protein KinasesMyocardial ContractionCardiotoxicityPhospholambanMice Inbred C57BL030104 developmental biologyDoxorubicinMilrinoneFemaleCardiology and Cardiovascular MedicineProto-Oncogene Proteins c-aktmedicine.drugCardiovascular research
researchProduct