2021
Targeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis
Knitz MW, Bickett TE, Darragh LB, Oweida AJ, Bhatia S, Van Court B, Bhuvane S, Piper M, Gadwa J, Mueller AC, Nguyen D, Nangia V, Osborne DG, Bai X, Ferrara SE, Boss MK, Goodspeed A, Burchill MA, Tamburini BAJ, Chan ED, Pickering CR, Clambey ET, Karam SD. Targeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis. Journal For ImmunoTherapy Of Cancer 2021, 9: e001955. PMID: 33883256, PMCID: PMC8061827, DOI: 10.1136/jitc-2020-001955.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, ImmunologicalBasic-Leucine Zipper Transcription FactorsCell Line, TumorCombined Modality TherapyDendritic CellsDrug Resistance, NeoplasmHead and Neck NeoplasmsImmune Checkpoint InhibitorsImmunotherapyInterleukin-2 Receptor alpha SubunitLymphocyte DepletionMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutPhenotypeRadiation Dose HypofractionationRadiation ToleranceRepressor ProteinsSquamous Cell Carcinoma of Head and NeckT-Lymphocytes, RegulatoryTumor BurdenTumor MicroenvironmentTumor Necrosis Factor Receptor Superfamily, Member 9ConceptsCombination radiation therapyRadiation therapyDendritic cellsLymph nodesMouse modelRadioresistant tumorsRegulatory T-cell depletionT cell effector responsesTumor-draining lymph nodesNeck squamous cell carcinomaOral squamous cell carcinoma tumorsT cell-dependent responsesSquamous cell carcinoma tumorsAnti-CD137 treatmentDC activation statusGy x 5Higher Treg numbersPlasticity of TregsAdoptive transfer studiesT-cell depletionSquamous cell carcinomaCell-dependent responsesOrthotopic mouse modelTumor necrosis factorαNew therapeutic opportunities
2020
Loss of p53 drives neuron reprogramming in head and neck cancer
Amit M, Takahashi H, Dragomir MP, Lindemann A, Gleber-Netto FO, Pickering CR, Anfossi S, Osman AA, Cai Y, Wang R, Knutsen E, Shimizu M, Ivan C, Rao X, Wang J, Silverman DA, Tam S, Zhao M, Caulin C, Zinger A, Tasciotti E, Dougherty PM, El-Naggar A, Calin GA, Myers JN. Loss of p53 drives neuron reprogramming in head and neck cancer. Nature 2020, 578: 449-454. PMID: 32051587, PMCID: PMC9723538, DOI: 10.1038/s41586-020-1996-3.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic AntagonistsAdrenergic NeuronsAnimalsCell DivisionCell TransdifferentiationCellular ReprogrammingDisease Models, AnimalDisease ProgressionFemaleHumansMaleMiceMice, Inbred BALB CMicroRNAsMouth NeoplasmsNerve FibersNeuritesReceptors, AdrenergicRetrospective StudiesSensory Receptor CellsTumor MicroenvironmentTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsOral cancerNerve fibersAdrenergic nerve fibersPoor clinical outcomeTrigeminal sensory neuronsLoss of TP53Sensory denervationAdrenergic nervesChemical sympathectomyNerve densitySensory nervesClinical outcomesSolid tumor microenvironmentLoss of p53Neck cancerPharmacological blockadeEndogenous neuronsRetrospective analysisMouse modelSensory neuronsAdrenergic phenotypeAdrenergic receptorsTumor growthTumor progressionTumor microenvironment
2017
Replication Stress Leading to Apoptosis within the S-phase Contributes to Synergism between Vorinostat and AZD1775 in HNSCC Harboring High-Risk TP53 Mutation
Tanaka N, Patel AA, Tang L, Silver NL, Lindemann A, Takahashi H, Jaksik R, Rao X, Kalu NN, Chen TC, Wang J, Frederick MJ, Johnson F, Gleber-Netto FO, Fu S, Kimmel M, Wang J, Hittelman WN, Pickering CR, Myers JN, Osman AA. Replication Stress Leading to Apoptosis within the S-phase Contributes to Synergism between Vorinostat and AZD1775 in HNSCC Harboring High-Risk TP53 Mutation. Clinical Cancer Research 2017, 23: 6541-6554. PMID: 28790110, PMCID: PMC5724758, DOI: 10.1158/1078-0432.ccr-17-0947.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCarcinoma, Squamous CellCell Cycle ProteinsCell Line, TumorCell ProliferationDNA DamageDNA ReplicationDrug SynergismFemaleHead and Neck NeoplasmsHistone Deacetylase InhibitorsHumansHydroxamic AcidsMiceMutationNuclear ProteinsPhosphorylationProtein-Tyrosine KinasesPyrazolesPyrimidinesPyrimidinonesRisk FactorsS PhaseSquamous Cell Carcinoma of Head and NeckTumor Suppressor Protein p53VorinostatConceptsOrthotopic mouse modelHNSCC cellsOral cancerMouse modelNeck squamous cell carcinomaSquamous cell carcinomaCombination of vorinostatProlongs animal survivalHNSCC cell linesClin Cancer ResClonogenic survival assaysAdvanced HNSCCAdvanced headStandard therapyCell carcinomaCure rateEffective therapyClinical investigationCell cycleP53 mutationsTumor growthVorinostatAnimal survivalAZD1775Cancer Res
2016
Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates
Chitsazzadeh V, Coarfa C, Drummond JA, Nguyen T, Joseph A, Chilukuri S, Charpiot E, Adelmann CH, Ching G, Nguyen TN, Nicholas C, Thomas VD, Migden M, MacFarlane D, Thompson E, Shen J, Takata Y, McNiece K, Polansky MA, Abbas HA, Rajapakshe K, Gower A, Spira A, Covington KR, Xiao W, Gunaratne P, Pickering C, Frederick M, Myers JN, Shen L, Yao H, Su X, Rapini RP, Wheeler DA, Hawk ET, Flores ER, Tsai KY. Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates. Nature Communications 2016, 7: 12601. PMID: 27574101, PMCID: PMC5013636, DOI: 10.1038/ncomms12601.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCarcinogenesisCarcinoma, Squamous CellDisease ProgressionDNA Mutational AnalysisExome SequencingFemaleGene Expression ProfilingGenomicsHigh-Throughput Nucleotide SequencingHumansKeratosis, ActinicMiceMice, HairlessMolecular Targeted TherapyPrecancerous ConditionsSequence Analysis, RNASkinSkin NeoplasmsUltraviolet RaysConceptsCross-species genomic analysisCross-species identificationCross-species analysisKey genomic changesGenomic analysisGenomic changesTranscriptional driversDistinct precancerous lesionsGenomic driversPotential targetSquamous cell carcinoma developmentMolecular similarityActinic keratosisAccessible modelDiverse sitesCutaneous squamous cell carcinomaHuman samplesSquamous cell carcinomaHairless mouse modelProgression sequenceMouse modelCarcinoma developmentCell carcinomaPrecancerous lesionsCommon treatment
2001
Is p53 Haploinsufficient for Tumor Suppression? Implications for the p53+/- Mouse Model in Carcinogenicity Testing
Venkatachalam S, Tyner S, Pickering C, Boley S, Recio L, French J, Donehower L. Is p53 Haploinsufficient for Tumor Suppression? Implications for the p53+/- Mouse Model in Carcinogenicity Testing. Toxicologic Pathology 2001, 29: 147-154. PMID: 11695551, DOI: 10.1080/019262301753178555.Peer-Reviewed Original ResearchConceptsEnhanced tumor susceptibilityWild-type p53 alleleP53-deficient miceMouse modelP53 alleleP53 dosageTumor susceptibilityTransgenic mouse modelWild-type littermatesDifferent tumor typesP53 tumor suppressor geneTumor suppressionP53 LOHTumor typesTumorsTumor suppressor geneMiceP53 lossHaploinsufficient tumor suppressorCarcinogenicity testingPreliminary dataOncogenic lesionsCancer formationMechanisms of genotoxicityTumor suppressor