2014
Acquired Resistance of EGFR-Mutant Lung Adenocarcinomas to Afatinib plus Cetuximab Is Associated with Activation of mTORC1
Pirazzoli V, Nebhan C, Song X, Wurtz A, Walther Z, Cai G, Zhao Z, Jia P, de Stanchina E, Shapiro EM, Gale M, Yin R, Horn L, Carbone DP, Stephens PJ, Miller V, Gettinger S, Pao W, Politi K. Acquired Resistance of EGFR-Mutant Lung Adenocarcinomas to Afatinib plus Cetuximab Is Associated with Activation of mTORC1. Cell Reports 2014, 7: 999-1008. PMID: 24813888, PMCID: PMC4074596, DOI: 10.1016/j.celrep.2014.04.014.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAfatinibAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorCetuximabDrug Resistance, NeoplasmErbB ReceptorsHumansLung NeoplasmsMechanistic Target of Rapamycin Complex 1MiceMice, NudeMice, TransgenicMultiprotein ComplexesMutationQuinazolinesRandom AllocationTOR Serine-Threonine KinasesXenograft Model Antitumor AssaysConceptsTyrosine kinase inhibitorsFirst-generation tyrosine kinase inhibitorEGFR-mutant lung adenocarcinomaLung adenocarcinomaMechanisms of resistanceEGFR antibody cetuximabPotential therapeutic strategyBiopsy specimensAntibody cetuximabDrug combinationsMouse modelTherapeutic strategiesAfatinibAddition of rapamycinCetuximabDual inhibitionAcquired ResistanceKinase inhibitorsGenomic alterationsAdenocarcinomaPatientsActivationGenomic mechanismsDrugsMTORC1 activationReduced NF1 Expression Confers Resistance to EGFR Inhibition in Lung Cancer
de Bruin EC, Cowell C, Warne PH, Jiang M, Saunders RE, Melnick MA, Gettinger S, Walther Z, Wurtz A, Heynen GJ, Heideman DA, Gómez-Román J, García-Castaño A, Gong Y, Ladanyi M, Varmus H, Bernards R, Smit EF, Politi K, Downward J. Reduced NF1 Expression Confers Resistance to EGFR Inhibition in Lung Cancer. Cancer Discovery 2014, 4: 606-619. PMID: 24535670, PMCID: PMC4011693, DOI: 10.1158/2159-8290.cd-13-0741.Peer-Reviewed Original ResearchConceptsLung cancerMAP-ERK kinase (MEK) inhibitorsEGF receptorEGFR-mutant lung adenocarcinomaKinase inhibitorsHuman lung cancer cell linesResistance of lungSubgroup of patientsLung cancer cell linesCancer cell linesClinical responsivenessCombination therapyEGFR-TKIEGFR mutationsErlotinib resistanceLung adenocarcinomaRAS-ERK signalingEGFR inhibitionMEK inhibitorsErlotinibReduced expressionNF1 expressionPatientsCell linesNeurofibromin levels
2012
MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice
Hoshi N, Schenten D, Nish SA, Walther Z, Gagliani N, Flavell RA, Reizis B, Shen Z, Fox JG, Iwasaki A, Medzhitov R. MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice. Nature Communications 2012, 3: 1120. PMID: 23047678, PMCID: PMC3521499, DOI: 10.1038/ncomms2113.Peer-Reviewed Original ResearchConceptsToll-like receptorsInterleukin-10Mononuclear phagocytesIL-10-deficient miceT helper 17 responsesColonic mononuclear phagocytesDevelopment of colitisInflammatory bowel diseaseColitis developmentBowel diseaseInterleukin-23MyD88 expressionInterleukin-1βInterleukin-6Intestinal homeostasisEpithelial expressionMyD88Multiple cell typesMiceCell typesReceptorsPhagocytesBacterial sensingDistinct populationsHigh levels
2011
Mitochondrial Genome Instability and ROS Enhance Intestinal Tumorigenesis in APCMin/+ Mice
Woo DK, Green PD, Santos JH, D'Souza AD, Walther Z, Martin WD, Christian BE, Chandel NS, Shadel GS. Mitochondrial Genome Instability and ROS Enhance Intestinal Tumorigenesis in APCMin/+ Mice. American Journal Of Pathology 2011, 180: 24-31. PMID: 22056359, PMCID: PMC3338350, DOI: 10.1016/j.ajpath.2011.10.003.Peer-Reviewed Original ResearchConceptsMitochondrial genome instabilityGenome instabilityMtDNA instabilityMaintenance of mtDNAMitochondrial transcription factor AMitochondrial dysfunctionIntestinal tumorigenesisTranscription factor AWnt/β-catenin signalingMitochondrial oxidative phosphorylationMitochondrial ROS productionΒ-catenin signalingOxidative mtDNA damageReactive oxygen species productionMitochondrial DNAOxygen species productionMouse cellsOxidative phosphorylationOvert phenotypeMitochondrial ROSMtDNA damageMtDNA depletionCancer phenotypeAltered amountsTumorigenesis
2009
CASK Deletion in Intestinal Epithelia Causes Mislocalization of LIN7C and the DLG1/Scrib Polarity Complex without Affecting Cell Polarity
Lozovatsky L, Abayasekara N, Piawah S, Walther Z. CASK Deletion in Intestinal Epithelia Causes Mislocalization of LIN7C and the DLG1/Scrib Polarity Complex without Affecting Cell Polarity. Molecular Biology Of The Cell 2009, 20: 4489-4499. PMID: 19726564, PMCID: PMC2770937, DOI: 10.1091/mbc.e09-04-0280.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorEpithelial polarityNormal localizationBasolateral membranePolarity complexMammalian orthologsCell polarityCaenorhabditis elegansMAGUK familyProtein complexesIntestinal epitheliumGrowth factor receptorLIN7CBasolateral localizationComplete knockoutCASK expressionTumor suppressorSubcellular distributionDlg1CASK deletionFactor receptorImmunofluorescence analysisErbB-2Intestinal homeostasisAppropriate localization