Search results for "Lung"

showing 10 items of 2389 documents

Amphiregulin contained in NSCLC-exosomes induces osteoclast differentiation through the activation of EGFR pathway

2017

AbstractNon-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. The majority of patients are diagnosed in advanced disease stage. Bone metastasis is the most frequent complication in NSCLC resulting in osteolytic lesions. The perfect balance between bone-resorbing osteoclasts and bone-forming osteoblasts activity is lost in bone metastasis, inducing osteoclastogenesis. In NSCLC, the epidermal growth factor receptor (EGFR) pathway is constitutively activated. EGFR binds Amphiregulin (AREG) that is overexpressed in several cancers such as colon, breast and lung. Its levels in plasma of NSCLC patients correlate with poor prognosis and AREG was recently …

0301 basic medicineLung NeoplasmsCellular differentiationAmphiregulin exosomes NSCLC EGFROsteoclastsExosomes NSCLC AmphiregulinNSCLCExosomesMice0302 clinical medicineSettore BIO/13 - Biologia ApplicataCarcinoma Non-Small-Cell LungMedicineEpidermal growth factor receptorRNA Small InterferingMultidisciplinarybiologyQProteolytic enzymesRBone metastasisCell Differentiation3. Good healthErbB ReceptorsGene Expression Regulation Neoplasticmedicine.anatomical_structureRANKL030220 oncology & carcinogenesisMedicineEngineering sciences. TechnologySciencePrimary Cell CultureBone NeoplasmsAmphiregulinArticle03 medical and health sciencesAmphiregulinOsteoclastCell Line TumorAnimalsHumansbusiness.industryRANK LigandBiological Transportmedicine.diseaseMicrovesiclesCoculture Techniquesrespiratory tract diseases030104 developmental biologyRAW 264.7 CellsImmunologybiology.proteinCancer researchbusiness
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PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer.

2018

The cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway detects cytosolic DNA to activate innate immune responses. Poly(ADP-ribose) polymerase inhibitors (PARPi) selectively target cancer cells with DNA repair deficiencies such as those caused by BRCA1 mutations or ERCC1 defects. Using isogenic cell lines and patient-derived samples, we showed that ERCC1-defective non-small cell lung cancer (NSCLC) cells exhibit an enhanced type I IFN transcriptomic signature and that low ERCC1 expression correlates with increased lymphocytic infiltration. We demonstrated that clinical PARPi, including olaparib and rucaparib, have cell-autonomous immunomodulatory properties in ERCC1-defecti…

0301 basic medicineLung NeoplasmsDNA repairPoly (ADP-Ribose) Polymerase-1Triple Negative Breast NeoplasmsPoly(ADP-ribose) Polymerase InhibitorsPoly (ADP-Ribose) Polymerase InhibitorB7-H1 AntigenOlaparib03 medical and health scienceschemistry.chemical_compoundInterferon-gamma0302 clinical medicinePARP1Carcinoma Non-Small-Cell LungHumansRucaparibA549 cellChemistryBRCA1 ProteinMembrane ProteinsGeneral MedicineEndonucleasesIsogenic human disease modelsNucleotidyltransferasesDNA-Binding Proteins030104 developmental biologyA549 Cells030220 oncology & carcinogenesisCancer cellCancer researchFemaleResearch ArticleThe Journal of clinical investigation
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Profile of the Roche cobas® EGFR mutation test v2 for non-small cell lung cancer

2017

Abstract: Introduction: The discovery of driver mutations in non-small cell lung cancer (NSCLC) has led to the development of genome-based personalized medicine. Fifteen to 20% of adenocarcinomas harbor an epidermal growth factor receptor (EGFR) activating mutation associated with responses to EGFR tyrosine kinase inhibitors (TKIs). Individual laboratories' expertise and the availability of appropriate equipment are valuable assets in predictive molecular pathology, although the choice of methods should be determined by the nature of the samples to be tested and whether the detection of only well-characterized EGFR mutations or rather, of all detectable mutations, is required.Areas covered:…

0301 basic medicineLung NeoplasmsEGFRDNA Mutational Analysis2734Real-Time Polymerase Chain Reactionmedicine.disease_causeBioinformaticsGenomePathology and Forensic Medicineresistance03 medical and health sciences0302 clinical medicineCarcinoma Non-Small-Cell LungGeneticsHumansMedicineEpidermal growth factor receptorLiquid biopsyLung cancerMolecular Biologycobas®Mutationliquid biopsybiologyReverse Transcriptase Polymerase Chain Reactionbusiness.industryMolecular pathologymedicine.diseaseTKIErbB Receptors030104 developmental biology030220 oncology & carcinogenesisCancer researchbiology.proteinMolecular Medicinecompanion diagnosticHuman medicineReagent Kits DiagnosticPersonalized medicinemutationbusinessCompanion diagnosticExpert Review of Molecular Diagnostics
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Genome-wide profiling of non-smoking-related lung cancer cells reveals common RB1 rearrangements associated with histopathologic transformation in EG…

2020

The etiology and the molecular basis of lung adenocarcinomas (LuADs) in nonsmokers are currently unknown. Furthermore, the scarcity of available primary cultures continues to hamper our biological understanding of non-smoking-related lung adenocarcinomas (NSK-LuADs). We established patient-derived cancer cell (PDC) cultures from metastatic NSK-LuADs, including two pairs of matched EGFR-mutant PDCs before and after resistance to tyrosine kinase inhibitors (TKIs), and then performed whole-exome and RNA sequencing to delineate their genomic architecture. For validation, we analyzed independent cohorts of primary LuADs. In addition to known non-smoker-associated alterations (e.g. RET, ALK, EGFR…

0301 basic medicineLung NeoplasmsEGFRUbiquitin-Protein LigasesAdenocarcinoma of Lungmedicine.disease_cause03 medical and health sciences0302 clinical medicineGermline mutationtyrosine kinase inhibitorsmedicineGenetic predispositionHumanswhole-exome sequencingLung cancerGeneProtein Kinase InhibitorsExome sequencingMutationbusiness.industryEGFR RB1 lung adenocarcinoma nonsmokers tyrosine kinase inhibitors whole-exome sequencingHematologyrespiratory systemmedicine.diseaselung adenocarcinomadigestive system diseasesrespiratory tract diseasesErbB ReceptorsRetinoblastoma Binding Proteins030104 developmental biologyOncologyDrug Resistance Neoplasm030220 oncology & carcinogenesisCancer cellMutationCancer researchbusinessRB1Tyrosine kinaseMicrotubule-Associated Proteinsnonsmokers
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MET-EGFR dimerization in lung adenocarcinoma is dependent on EGFR mtations and altered by MET kinase inhibition

2017

Advanced lung cancer has poor survival with few therapies. EGFR tyrosine kinase inhibitors (TKIs) have high response rates in patients with activating EGFR mutations, but acquired resistance is inevitable. Acquisition of the EGFR T790M mutation causes over 50% of resistance; MET amplification is also common. Preclinical data suggest synergy between MET and EGFR inhibitors. We hypothesized that EGFR-MET dimerization determines response to MET inhibition, depending on EGFR mutation status, independently of MET copy number. We tested this hypothesis by generating isogenic cell lines from NCI-H1975 cells, which co-express L858R and T790M EGFR mutations, namely H1975L858R/T790M (EGFR TKI resista…

0301 basic medicineLung NeoplasmsKinase InhibitorsCancer Treatmentlcsh:MedicinePhysical ChemistryBiochemistryFluorophotometryT790MSpectrum Analysis Techniques0302 clinical medicineFluorescence Resonance Energy TransferMedicine and Health SciencesPhosphorylationEnzyme Inhibitorslcsh:ScienceExtracellular Signal-Regulated MAP KinasesEGFR inhibitorsStainingMice Inbred BALB CMultidisciplinaryFluorescent in Situ HybridizationPhysicsCell StainingProto-Oncogene Proteins c-metPrecipitation TechniquesErbB ReceptorsChemistryOncologySpectrophotometry030220 oncology & carcinogenesisPhysical SciencesErlotinibDimerizationProtein BindingResearch Articlemedicine.drugChemical physicsMice NudeMolecular Probe TechniquesAdenocarcinoma of LungAdenocarcinomaBiologyResearch and Analysis Methods03 medical and health sciencesGefitinibGrowth factor receptorCell Line TumormedicineAnimalsHumansImmunoprecipitationMolecular Biology TechniquesLung cancerProtein Kinase InhibitorsMolecular BiologyCell ProliferationCell growthlcsh:RReproducibility of ResultsBiology and Life SciencesDimers (Chemical physics)medicine.diseaseMolecular biologyIsogenic human disease modelsProbe Hybridizationrespiratory tract diseasesHEK293 Cells030104 developmental biologyChemical PropertiesSpecimen Preparation and TreatmentFocal Adhesion Protein-Tyrosine KinasesMutationEnzymologylcsh:QProtein MultimerizationProto-Oncogene Proteins c-aktCytogenetic TechniquesPLOS ONE
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A molecular hypothesis to explain direct and inverse co-morbidities between Alzheimer's Disease, Glioblastoma and Lung cancer.

2017

Epidemiological studies indicate that patients suffering from Alzheimer’s disease have a lower risk of developing lung cancer, and suggest a higher risk of developing glioblastoma. Here we explore the molecular scenarios that might underlie direct and inverse co-morbidities between these diseases. Transcriptomic meta-analyses reveal significant numbers of genes with inverse patterns of expression in Alzheimer’s disease and lung cancer, and with similar patterns of expression in Alzheimer’s disease and glioblastoma. These observations support the existence of molecular substrates that could at least partially account for these direct and inverse co-morbidity relationships. A functional analy…

0301 basic medicineLung NeoplasmsMolecular biology[SDV]Life Sciences [q-bio]Gene ExpressionDiseaseCàncer--Fisiologia patològicaComorbidityTranscriptomeMedicineDinàmica molecularMultidisciplinaryQLung Cancer:Enginyeria biomèdica [Àrees temàtiques de la UPC]R3. Good healthAlzheimer's disease (AD)MedicineDisease SusceptibilityAlzheimer's diseaseSignal transductionSignal TransductionCentral Nervous System (CNS)ScienceModels BiologicalArticle03 medical and health sciencesImmune systemcáncerAlzheimer DiseaseDementia[CHIM]Chemical SciencesHumansLung cancerbusiness.industryGenetic Variationmedicine.diseaseComorbidityCNS cancerAlzheimer Malaltia d'030104 developmental biologyGliobastomas (GBM)ImmunologyCancer researchDementiabusinessGlioblastomaReactive Oxygen SpeciesNon-small-cell lung cancerBiomarkers
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The potential of neurotrophic tyrosine kinase (NTRK) inhibitors for treating lung cancer

2016

Abstract: Introduction: Molecular alterations in neurotrophic tyrosine kinase (NTRK) genes have been identified in several solid tumors including lung cancer. Pre-clinical and clinical evidence suggested their potential role as oncogenic drivers and predictive biomarkers for targeted inhibition, leading to the clinical development of a new class of compounds blocking the NTRK molecular pathway, which are currently undner early clinical investigation. Area covered: This review describes the biology of the NTRK pathway and its molecular alterations in lung cancer. It focuses on the pre-clinical and clinical development of emerging NTRK inhibitors, which have shown very promising activity in e…

0301 basic medicineLung NeoplasmsNTRKinhibitorsNTRK1/2/3Settore MED/06 - Oncologia Medicamedicine.medical_treatmentReceptor Protein-Tyrosine KinasesEntrectinibPharmacologyTargeted therapy03 medical and health sciences0302 clinical medicineMedicineAnimalsHumansPharmacology (medical)In patientNTRKinhibitorLung cancerProtein Kinase InhibitorsTrkA/B/CPharmacologyNTRK1/2/3; TrkA/B/C; NTRKinhibitors; targeted therapy; lung cancerbiologybusiness.industryPharmacology. TherapyReceptor Protein-Tyrosine KinasesGeneral Medicinemedicine.diseasetargeted therapySettore CHIM/08 - Chimica Farmaceuticalung cancer030104 developmental biology030220 oncology & carcinogenesisbiology.proteinCancer researchbusinessEarly phaseTyrosine kinaseNeurotrophin
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Central nervous system involvement in ALK-rearranged NSCLC : promising strategies to overcome crizotinib resistance

2016

ABSTRACT: Introduction: ALK rearranged Non Small Cell Lung Cancers (NSCLCs) represent a distinct subgroup of patients with peculiar clinic-pathological features. These patients exhibit dramatic responses when treated with the ALK tyrosine kinase inhibitor Crizotinib, albeit Central Nervous System (CNS) activity is much less impressive than that observed against extracranial lesions. CNS involvement has become increasingly observed in these patients, given their prolonged survival. Several novel generation ALK inhibitors have been developing to increase CNS penetration and to provide more complete ALK inhibition. Areas covered: The CNS activity of Crizotinib and novel generation ALK inhibito…

0301 basic medicineLung NeoplasmsSettore MED/06 - Oncologia MedicaPyridinesPyridineDrug ResistanceNSCLCTyrosine-kinase inhibitorALK translocations Brain metastases central nervous system metastases leptomeningeal metastases NSCLC Animals Antineoplastic Agents Brain Neoplasms Carcinoma Non-Small-Cell Lung Drug Design Drug Resistance Neoplasm Gene Rearrangement Humans Lung Neoplasms Protein Kinase Inhibitors Pyrazoles Pyridines Receptor Protein-Tyrosine Kinases Oncology Pharmacology (medical)Cns penetrationAntineoplastic Agent0302 clinical medicinecentral nervous system metastasesCarcinoma Non-Small-Cell Lunghemic and lymphatic diseasesMedicinePharmacology (medical)Anaplastic Lymphoma Kinaseleptomeningeal metastaseNon-Small-Cell LungGene RearrangementBrain NeoplasmsReceptor Protein-Tyrosine Kinasemedicine.anatomical_structureOncology030220 oncology & carcinogenesisNon small cellHumanmedicine.drugBrain metastasemedicine.drug_classCentral nervous systemProtein Kinase InhibitorCNS InvolvementAntineoplastic AgentsALK translocationBrain Neoplasm03 medical and health sciencesCrizotinibAnimalsHumansCns activityCrizotinib resistanceProtein Kinase Inhibitorsleptomeningeal metastasescentral nervous system metastaseCrizotinibAnimalbusiness.industryCarcinomaReceptor Protein-Tyrosine KinasesBrain metastasesLung Neoplasm030104 developmental biologyALK translocationsDrug Resistance NeoplasmDrug DesignPyrazoleImmunologyCancer researchNeoplasmPyrazolesHuman medicinebusinessExpert review of anticancer therapy
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Comprehensive Analysis of SWI/SNF Inactivation in Lung Adenocarcinoma Cell Models

2020

Simple Summary: Mammalian SWI/SNF complexes regulate gene expression by reorganizing the way DNA is packaged into chromatin. SWI/SNF subunits are recurrently altered in tumors at multiple levels, including DNA mutations as well as alteration of the levels of RNA and protein. Cancer cell lines are often used to study SWI/SNF function, but their patterns of SWI/SNF alterations can be complex. Here, we present a comprehensive characterization of DNA mutations and RNA and protein expression of SWI/SNF members in 38 lung adenocarcinoma (LUAD) cell lines. We show that over 85% of our cell lines harbored at least one alteration in one SWI/SNF subunit. In addition, over 75% of our cell lines lacked…

0301 basic medicineLung adenocarcinomaCancer ResearchcellsCellgenetic processesmacromolecular substancesBiologylcsh:RC254-282Articlelaw.inventionTranscriptome03 medical and health sciences0302 clinical medicinelawmedicineEpigeneticsMulti-omicsSWI/SNF complexepigeneticsCancermulti-omicslcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogensmedicine.diseaselung adenocarcinomaSWI/SNFcell models3. Good healthCell biologyChromatinenzymes and coenzymes (carbohydrates)lung cancer030104 developmental biologymedicine.anatomical_structureOncology030220 oncology & carcinogenesisCell modelSuppressorEpigeneticsbiological phenomena cell phenomena and immunityLung cancerSWI/SNF complex
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Microenvironmental Th9 and Th17 lymphocytes induce metastatic spreading in lung cancer.

2020

Immune microenvironment plays a critical role in lung cancer control versus progression and metastasis. In this investigation, we explored the effect of tumor-infiltrating lymphocyte subpopulations on lung cancer biology by studying in vitro cocultures, in vivo mouse models, and human lung cancer tissue. Lymphocyte conditioned media (CM) induced epithelial-mesenchymal transition (EMT) and migration in both primary human lung cancer cells and cell lines. Correspondingly, major accumulation of Th9 and Th17 cells was detected in human lung cancer tissue and correlated with poor survival. Coculturing lung cancer cells with Th9/Th17 cells or exposing them to the respective CM induced EMT in canc…

0301 basic medicineLymphocyteT cellsInflammationMetastasis03 medical and health sciences0302 clinical medicinemedicineLung cancerCancerInflammationbiologybusiness.industryCancerGeneral Medicinemedicine.disease030104 developmental biologymedicine.anatomical_structureOncologyCell culture030220 oncology & carcinogenesisCancer cellbiology.proteinCancer researchmedicine.symptomAntibodybusiness
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