Search results for "Mitogen-Activated Protein Kinase Phosphatases"

showing 2 items of 2 documents

IL4 Primes the Dynamics of Breast Cancer Progression via DUSP4 Inhibition

2017

Abstract The tumor microenvironment supplies proinflammatory cytokines favoring a permissive milieu for cancer cell growth and invasive behavior. Here we show how breast cancer progression is facilitated by IL4 secreted by adipose tissue and estrogen receptor–positive and triple-negative breast cancer cell types. Blocking autocrine and paracrine IL4 signaling with the IL4Rα antagonist IL4DM compromised breast cancer cell proliferation, invasion, and tumor growth by downregulating MAPK pathway activity. IL4DM reduced numbers of CD44+/CD24− cancer stem-like cells and elevated expression of the dual specificity phosphatase DUSP4 by inhibiting NF-κB. Enforced expression of DUSP4 drove conversio…

0301 basic medicineCancer ResearchBlotting WesternCA 15-3Breast Neoplasms03 medical and health sciencesParacrine signalling0302 clinical medicineBreast cancerCell Line TumorTumor MicroenvironmentmedicineHumansskin and connective tissue diseasesAutocrine signallingDual-Specificity PhosphataseBlotting Western; Breast Neoplasms; Cell Line Tumor; Disease Progression; Dual-Specificity Phosphatases; Female; Flow Cytometry; Heterografts; Humans; Interleukin-4; Mitogen-Activated Protein Kinase Phosphatases; Tumor Microenvironment; Oncology; Cancer ResearchTumor microenvironmentbiologyCD44CancerFlow Cytometrymedicine.disease030104 developmental biologyOncology030220 oncology & carcinogenesisImmunologyCancer cellDisease Progressionbiology.proteinCancer researchDual-Specificity PhosphatasesHeterograftsMitogen-Activated Protein Kinase PhosphatasesFemaleInterleukin-4HeterograftMitogen-Activated Protein Kinase PhosphataseBreast NeoplasmHumanCancer Research
researchProduct

Roflumilast N-oxide reverses corticosteroid resistance in neutrophils from patients with chronic obstructive pulmonary disease

2013

Background Glucocorticoid functions are markedly impaired in patients with chronic obstructive pulmonary disease (COPD). The phosphodiesterase 4 inhibitor roflumilast N-oxide (RNO) is the active metabolite of roflumilast approved as a treatment to reduce the risk of exacerbations in patients with severe COPD. Objective We sought to characterize the differential effects of RNO versus corticosteroids and their potential additive/synergistic effect in neutrophils from patients with COPD, thus providing scientific rationale for the combination of roflumilast with corticosteroids in the clinic. Methods Peripheral blood neutrophils were isolated from patients with COPD (n = 32), smokers (n = 7), …

CyclopropanesLipopolysaccharidesMaleMAPK/ERK pathwaymedicine.medical_specialtyNeutrophilsPrimary Cell CultureImmunologyDrug ResistanceAminopyridinesGene ExpressionComplex MixturesDexamethasoneHistone DeacetylasesPhosphatidylinositol 3-KinasesPulmonary Disease Chronic ObstructiveGlucocorticoid receptorAdrenal Cortex HormonesInternal medicineTobaccomedicineHumansImmunology and AllergyMacrophage Migration-Inhibitory FactorsDexamethasoneActive metaboliteRoflumilastAgedCOPDbusiness.industryInterleukin-8Drug SynergismMiddle Agedmedicine.diseaseIntramolecular OxidoreductasesEndocrinologyMatrix Metalloproteinase 9BenzamidesMitogen-Activated Protein Kinase PhosphatasesFemaleMacrophage migration inhibitory factorPhosphodiesterase 4 InhibitorsbusinessBiomarkersGlucocorticoidmedicine.drugJournal of Allergy and Clinical Immunology
researchProduct