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 ResDistinct pattern of TP53 mutations in human immunodeficiency virus–related head and neck squamous cell carcinoma
Gleber‐Netto F, Zhao M, Trivedi S, Wang J, Jasser S, McDowell C, Kadara H, Zhang J, Wang J, William WN, Lee JJ, Nguyen ML, Pai SI, Walline HM, Shin DM, Ferris RL, Carey TE, Myers JN, Pickering CR, Consortium F. Distinct pattern of TP53 mutations in human immunodeficiency virus–related head and neck squamous cell carcinoma. Cancer 2017, 124: 84-94. PMID: 29053175, PMCID: PMC5785080, DOI: 10.1002/cncr.31063.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCadherinsCarcinoma, Squamous CellCase-Control StudiesCaspase 8Class I Phosphatidylinositol 3-KinasesCyclin D1Cyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18ErbB ReceptorsF-Box-WD Repeat-Containing Protein 7FemaleHead and Neck NeoplasmsHistone MethyltransferasesHistone-Lysine N-MethyltransferaseHIV InfectionsHLA-A AntigensHumansIn Situ HybridizationIntracellular Signaling Peptides and ProteinsKelch-Like ECH-Associated Protein 1LIM Domain ProteinsMaleMiddle AgedNF-E2-Related Factor 2Nuclear ProteinsPapillomaviridaePapillomavirus InfectionsProtein Serine-Threonine KinasesProto-Oncogene Proteins p21(ras)Receptor, Notch1Receptor, Notch2Receptor, Transforming Growth Factor-beta Type IIReceptors, Transforming Growth Factor betaSquamous Cell Carcinoma of Head and NeckTranscription FactorsTumor Suppressor Protein p53Tumor Suppressor ProteinsConceptsHuman immunodeficiency virus-infected individualsHuman immunodeficiency virus (HIV) infectionNeck squamous cell carcinomaHuman papillomavirus (HPV) statusImmunodeficiency virus infectionVirus-infected individualsSquamous cell carcinomaSample of HIVTP53 mutation frequencyHNSCC patientsCell carcinomaHistopathological differencesPolymerase chain reactionIon Reporter softwareP16 immunostainingDistinct biologyVirus infectionHigh incidenceHIVHNSCCMultiplex polymerase chain reactionDistinct patternsHIV virusTumor samplesTP53 geneMutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors
Zhang M, Singh R, Peng S, Mazumdar T, Sambandam V, Shen L, Tong P, Li L, Kalu NN, Pickering CR, Frederick M, Myers JN, Wang J, Johnson FM. Mutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors. Cancer Letters 2017, 392: 71-82. PMID: 28126323, PMCID: PMC5404895, DOI: 10.1016/j.canlet.2017.01.024.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsApoptosisCarcinoma, Squamous CellCell Cycle ProteinsCell Line, TumorCell ProliferationCheckpoint Kinase 1Checkpoint Kinase 2Dose-Response Relationship, DrugG2 Phase Cell Cycle CheckpointsGenotypeHead and Neck NeoplasmsHumansLIM Domain ProteinsMice, NudeMolecular Targeted TherapyMutationNuclear ProteinsPhenotypeProtein Kinase InhibitorsProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene ProteinsPteridinesPyrazolesPyrimidinesPyrimidinonesRas ProteinsRNA InterferenceSignal TransductionSmad4 ProteinSquamous Cell Carcinoma of Head and NeckThiophenesTime FactorsTransfectionTumor BurdenUreaXenograft Model Antitumor AssaysConceptsPolo-like kinase 1Cell linesLIM protein AjubaHNSCC cell linesInhibitor-induced apoptosisProtein expressionCell cycle inhibitorsCell cycle arrestKnockdown of PLK1Neck squamous cell carcinomaAjubaExogenous expressionNeck squamous cell carcinoma (HNSCC) tumorsSquamous cell carcinoma tumorsKinase 1HNSCC mouse modelSquamous cell carcinomaSubstrate inhibitionHigher drug dosesPotential candidate biomarkersGenomic alterationsMitotic inhibitorsPLK1 inhibitionSensitive cell linesMutations