Search results for "Signaling System"

showing 10 items of 105 documents

Effects of carboxyamidotriazole on in vitro models of imatinib-resistant chronic myeloid leukemia.

2008

Although imatinib mesylate (IM) has revolutionized the treatment of chronic myeloid leukemia (CML), some patients develop resistance with progression of leukemia. Alternative or additional targeting of signaling pathways deregulated in bcr-abl-driven CML cells may provide a feasible option for improving clinical response and overcoming resistance. In this study, we show that carboxyamidotriazole (CAI), an orally bioavailable calcium influx and signal transduction inhibitor, is equally effective in inhibiting the proliferation and bcr-abl dependent- and independent-signaling pathways in imatinib-resistant CML cells. CAI inhibits phosphorylation of cellular proteins including STAT5 and CrkL a…

PhysiologyMAP Kinase Signaling SystemClinical BiochemistryFusion Proteins bcr-ablDown-RegulationApoptosisSignal transduction inhibitorPharmacologyPiperazineschemistry.chemical_compoundhemic and lymphatic diseasesCell Line TumorLeukemia Myelogenous Chronic BCR-ABL PositivemedicineHumansEnzyme InhibitorsPhosphotyrosineCMLneoplasmsIn Situ Hybridization FluorescenceChronic Myelogenous LeukemiaCell ProliferationCarboxyamidotriazolebusiness.industryCAIMyeloid leukemiaImatinibCell BiologyTriazolesmedicine.diseaseCRKLEnzyme ActivationGene Expression Regulation NeoplasticLeukemiaImatinib mesylatePyrimidineschemistryDrug Resistance NeoplasmMolecular ProbesBenzamidesimatinib resistanceImatinib Mesylateras ProteinsCML; imatinib resistance; CAICarboxyamidotriazolebusinesssignal transductionChronic myelogenous leukemiamedicine.drugJournal of cellular physiology
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Influence of organophosphate poisoning on human dendritic cells.

2013

Organophosphourus compounds (OPC, including nerve agents and pesticides) exhibit acute toxicity by inhibition of acetylcholinesterase. Lung affections are frequent complications and a risk factor for death. In addition, epidemiological studies reported immunological alterations after OPC exposure. In our experiments we investigated the effects of organophosphourus pesticides dimethoate and chlorpyrifos on dendritic cells (DC) that are essential for the initial immune response, especially in the pulmonary system. DC, differentiated from the monocyte cell line THP-1 by using various cytokines (IL-4, GM-CSF, TNF-α, Ionomycin), were exposed to organophosphourus compounds at different concentrat…

Programmed cell deathInsecticidesMAP Kinase Signaling Systemmedicine.medical_treatmentPoison controlPharmacologyToxicologyMonocytesProinflammatory cytokineCell Linechemistry.chemical_compoundOrganophosphate PoisoningmedicineHumansDimethoatePesticidesProtein kinase BCell Deathbusiness.industryMonocyteCell DifferentiationGeneral MedicineDendritic cellDendritic Cellsmedicine.anatomical_structureCytokinechemistryImmunologyIonomycinCytokinesChlorpyrifosbusinessChemico-biological interactions
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Parthenolide induces caspase-independent and AIF-mediated cell death in human osteosarcoma and melanoma cells

2013

The mechanism of the cytotoxic effect exerted by parthenolide on tumor cells is not clearly defined today. This article shows that parthenolide stimulates in human osteosarcoma MG63 and melanoma SK-MEL-28 cells a mechanism of cell death, which is not prevented by z-VAD-fmk and other caspase inhibitors. In particular treatment with parthenolide rapidly stimulated (1-2 h) reactive oxygen species (ROS) generation by inducing activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) and NADPH oxidase. This event caused depletion of thiol groups and glutathione, NF-κB inhibition, c-Jun N-terminal kinase (JNK) activation, cell detachment from the matrix, and cellular shrinkage. The increa…

Programmed cell deathMAP Kinase Signaling SystemPhysiologyClinical BiochemistryAmino Acid Chloromethyl Ketoneschemistry.chemical_compoundCell Line TumorSettore BIO/10 - BiochimicaHumansParthenolidePropidium iodideFragmentation (cell biology)MelanomaCaspaseOsteosarcomaCell DeathbiologyNF-kappa BApoptosis Inducing FactorNADPH OxidasesCell BiologyCaspase InhibitorsCell biologyGene Expression Regulation NeoplasticchemistryApoptosisCell cultureCaspasesbiology.proteinApoptosis-inducing factorReactive Oxygen SpeciesSesquiterpenesParthenolide caspase-independent cell death ROS AIFJournal of Cellular Physiology
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Decreased SAPK/JNK signalling affects cytokine release and STAT3 activation in psoriatic fibroblasts.

2015

STAT3 Transcription FactorMAP Kinase Signaling Systemmedicine.medical_treatmentDermatologyBiochemistryp38 Mitogen-Activated Protein KinasesPsoriasismedicineSapk jnkHumansPsoriasisPhosphorylationSTAT3Molecular BiologyStat3 activationMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3biologyChemistryInterleukin-6Tumor Necrosis Factor-alphaInterleukin-8JNK Mitogen-Activated Protein KinasesTranscription Factor RelAFibroblastsmedicine.diseaseSignallingCytokineCase-Control StudiesCancer researchbiology.proteinPhosphorylationTumor necrosis factor alphaExperimental dermatology
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The mitotic kinase Aurora-A promotes distant metastases by inducing epithelial-to-mesenchymal transition in ERα+ breast cancer cells

2013

In this study, we demonstrate that constitutive activation of Raf-1 oncogenic signaling induces stabilization and accumulation of Aurora-A mitotic kinase that ultimately drives the transition from an epithelial to a highly invasive mesenchymal phenotype in estrogen receptor α-positive (ERα(+)) breast cancer cells. The transition from an epithelial- to a mesenchymal-like phenotype was characterized by reduced expression of ERα, HER-2/Neu overexpression and loss of CD24 surface receptor (CD24(-/low)). Importantly, expression of key epithelial-to-mesenchymal transition (EMT) markers and upregulation of the stemness gene SOX2 was linked to acquisition of stem cell-like properties such as the ab…

Smad5 ProteinCancer ResearchEpithelial-Mesenchymal TransitionMAP Kinase Signaling SystemReceptor ErbB-2Active Transport Cell NucleusEstrogen receptorMice NudeBreast NeoplasmsBiologyArticleMicebreast cancerSOX2Cell MovementCell Line TumorGeneticsAnimalsHumansEpithelial–mesenchymal transitionKinase activityNeoplasm MetastasisPhosphorylationRNA Small InterferingMolecular BiologyAurora Kinase Ametastases mitosisSOXB1 Transcription FactorsEstrogen Receptor alphaCD24 AntigenXenograft Model Antitumor AssaysstemneGene Expression Regulation NeoplasticProto-Oncogene Proteins c-rafSettore BIO/18 - GeneticaTumor progressionembryonic structuresCancer researchMCF-7 CellsNeoplastic Stem CellsProto-Oncogene Proteins c-rafFemaleRNA InterferenceSignal transductionEstrogen receptor alphaNeoplasm Transplantation
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A systems biology perspective on cholangiocellular carcinoma development: focus on MAPK-signaling and the extracellular environment.

2008

Background/Aims Multiple genes have been implicated in cholangiocellular carcinoma (CCC) development. However, the overall neoplastic risk is likely associated with a much lower number of critical physiological pathways. Methods To investigate this hypothesis, we extracted all published genetic associations for the development of CCC from PubMed (genetic association studies, but also studies associating genes and CCC in general, i.e. functional studies in cell lines, genetic studies in humans, knockout mice etc.) and integrated CCC microarray data. Results We demonstrated the MAPK pathway was consistently enriched in CCC. Comparing our data to genetic associations in HCC often successfully …

SorafenibMAPK/ERK pathwayNiacinamideMAP Kinase Signaling SystemPyridinesSystems biologyAntineoplastic AgentsOncogenomicsBiologyCholangiocarcinomaMiceDatabases GeneticmedicineAnimalsHumansGeneOligonucleotide Array Sequence AnalysisHepatologyMicroarray analysis techniquesKinasePhenylurea CompoundsSystems BiologyBenzenesulfonatesComputational BiologySorafenibBiological EvolutionBile Ducts IntrahepaticBile Duct NeoplasmsMultigene FamilyImmunologyKnockout mouseCancer researchExtracellular Spacemedicine.drugJournal of hepatology
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Hematopoietic stem cell quiescence and function are controlled by the CYLD–TRAF2–p38MAPK pathway

2015

Tesio at al. identify a novel pathway controlled by the tumor suppressor and deubiquitinase cylindromatosis (CYLD), which is involved in the regulation of hematopoietic stem cell quiescence and repopulation potential.

TRAF2Tumor suppressor geneMAP Kinase Signaling SystemImmunologyRegulatorBiologyp38 Mitogen-Activated Protein KinasesArticleMicemedicineAnimalsImmunology and AllergyMice KnockoutRegulation of gene expressionNF-kappa BHematopoietic stem cellCell BiologyHematopoietic Stem CellsTNF Receptor-Associated Factor 2PhenotypeDeubiquitinating Enzyme CYLDCell biologyCysteine EndopeptidasesHaematopoiesismedicine.anatomical_structureGene Expression RegulationMutationStem cellJournal of Experimental Medicine
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Acidic Environment Leads to ROS-Induced MAPK Signaling in Cancer Cells

2011

Tumor micromilieu often shows pronounced acidosis forcing cells to adapt their phenotype towards enhanced tumorigenesis induced by altered cellular signalling and transcriptional regulation. In the presents study mechanisms and potential consequences of the crosstalk between extra- and intracellular pH (pH(e), pH(i)) and mitogen-activated-protein-kinases (ERK1/2, p38) was analyzed. Data were obtained mainly in AT1 R-3327 prostate carcinoma cells, but the principle importance was confirmed in 5 other cell types. Extracellular acidosis leads to a rapid and sustained decrease of pH(i) in parallel to p38 phosphorylation in all cell types and to ERK1/2 phosphorylation in 3 of 6 cell types. Furth…

Tumor PhysiologyIntracellular Spacelcsh:MedicineSignal transductionERK signaling cascadeMolecular cell biologyNeoplasmsBasic Cancer ResearchTumor MicroenvironmentSignaling in Cellular ProcessesPhosphorylationCyclic AMP Response Element-Binding ProteinCreb Signalinglcsh:ScienceCellular Stress ResponsesMultidisciplinaryKinaseMechanisms of Signal TransductionSignaling cascadesHydrogen-Ion ConcentrationProtein-Tyrosine KinasesCell biologyOncologyMedicinePhosphorylationMitogen-Activated Protein KinasesSodium-Potassium-Exchanging ATPaseIntracellularResearch ArticleCell SurvivalMAP Kinase Signaling Systemp38 mitogen-activated protein kinasesIntracellular pHBiologyCREBModels BiologicalCell GrowthDogsCell Line TumorAnimalsHumansProtein Kinase InhibitorsBiologyPI3K/AKT/mTOR pathwaylcsh:RRatsEnzyme ActivationCancer cellbiology.proteinlcsh:QExtracellular SpaceReactive Oxygen SpeciesAcidsPLoS ONE
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Reactive oxygen species activation of MAPK pathway results in VEGF upregulation as an undesired irradiation response

2013

Background Radioresistance limits the effectiveness of radiotherapy in head and neck squamous cell carcinoma. We previously demonstrated post-radiogenic mitogen-activated protein kinase (MAPK) pathway activation and vascular endothelial growth factor (VEGF) release resulting in reduced tumor cell response. Here, we examined the association of this mechanism with the induction of reactive oxygen species (ROS) under irradiation (IR). Methods Intracellular ROS after IR were measured. We modeled radiation-induced ROS by exposure of two SCC lines to H2O2 and evaluated the impact of irradiation and ROS on ERK phosphorylation by Western blot, immunohistochemistry, and ELISA. Results We found eleva…

Vascular Endothelial Growth Factor AMAPK/ERK pathwayCancer ResearchPathologymedicine.medical_specialtyMAP Kinase Signaling SystemBlotting WesternEnzyme-Linked Immunosorbent AssayBiologyRadiation TolerancePathology and Forensic Medicinechemistry.chemical_compoundDownregulation and upregulationCell Line TumorNitrilesButadienesmedicineHumansEnzyme InhibitorsExtracellular Signal-Regulated MAP KinasesProtein kinase Achemistry.chemical_classificationReactive oxygen speciesHydrogen PeroxideImmunohistochemistryCytoprotectionUp-RegulationVascular endothelial growth factorVascular endothelial growth factor AOtorhinolaryngologychemistryCytoprotectionCarcinoma Squamous CellCancer researchPeriodonticsElectrophoresis Polyacrylamide GelOral SurgeryReactive Oxygen SpeciesIntracellularJournal of Oral Pathology & Medicine
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Activation of mitogen-activated protein kinase extracellular signal-related kinase in head and neck squamous cell carcinomas after irradiation as par…

2010

Background. Irradiation plays a pivotal role in head and neck squamous cell carcinoma (HNSCC) treatment. However, especially recurrent tumors frequently show increased radioresistance. We analyzed irradiation-stimulated mitogen-activated protein kinase (MAPK) signaling pathways to define cellular rescue mechanisms. Methods. Irradiated HNSCC cells were screened for MAPK activation and results were confirmed and refined by functional analyses. Extracellular signal-regulated kinase (ERK) inhibitor U0126 application enabled us to specify postradiogenic cellu- lar responses. Vascular endothelial growth factor (VEGF) levels were analyzed additionally. Results. We observed a pronounced and time-de…

Vascular Endothelial Growth Factor AMAPK/ERK pathwayMAP Kinase Signaling SystemMice NudeMicechemistry.chemical_compoundCell Line TumorRadioresistanceNitrilesButadienesmedicineAnimalsHumansEnzyme InhibitorsExtracellular Signal-Regulated MAP KinasesProtein kinase AbiologyKinasebusiness.industryRadiotherapy Dosagemedicine.diseaseImmunohistochemistryHead and neck squamous-cell carcinomaUp-RegulationVascular endothelial growth factorOtorhinolaryngologychemistryHead and Neck NeoplasmsMitogen-activated protein kinaseCarcinoma Squamous CellCancer researchbiology.proteinMitogen-Activated Protein KinasesSignal transductionbusinessNeoplasm TransplantationSignal TransductionHead & Neck
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