2022
The Role of PARP‐1 and NF‐κB in Bile‐Induced DNA Damage and Oncogenic Profile in Hypopharyngeal Cells
Doukas PG, Vageli DP, Judson BL. The Role of PARP‐1 and NF‐κB in Bile‐Induced DNA Damage and Oncogenic Profile in Hypopharyngeal Cells. The Laryngoscope 2022, 133: 1146-1155. PMID: 35791892, DOI: 10.1002/lary.30284.Peer-Reviewed Original ResearchConceptsHypopharyngeal cellsAcidic bileNF-κBNF-κB activationGamma-H2A histone family member XHypopharyngeal squamous cell carcinomaOncogenic profileNuclear factor kappa BPARP-1Squamous cell carcinomaB-cell lymphoma 2 expressionNF-κB transcriptional activityFactor kappa BDNA damageEnzyme-linked immunosorbent assayH2A histone family member XCell survivalDNA/RNA damageHypopharyngeal carcinogenesisReflux contentsAnti-apoptotic phenotypeCell carcinomaWidespread DNA damageBAY 11PARP-1 overexpressionNoxious Combination of Tobacco Smoke Nitrosamines with Bile, Deoxycholic Acid, Promotes Hypopharyngeal Squamous Cell Carcinoma, via NFκB, In Vivo.
Vageli DP, Doukas PG, Doukas SG, Tsatsakis A, Judson BL. Noxious Combination of Tobacco Smoke Nitrosamines with Bile, Deoxycholic Acid, Promotes Hypopharyngeal Squamous Cell Carcinoma, via NFκB, In Vivo. Cancer Prevention Research 2022, 15: 297-308. PMID: 35502554, DOI: 10.1158/1940-6207.capr-21-0529.Peer-Reviewed Original ResearchConceptsHypopharyngeal squamous cell carcinomaTobacco smoke componentsSquamous cell carcinomaAerodigestive tract carcinogenesisBile refluxRisk factorsHypopharyngeal cancerCell carcinomaChronic exposureNFκB activationVivo modelUpper aerodigestive tract cancerNoxious combinationLarge-scale studiesIndependent risk factorAerodigestive tract cancerUpper aerodigestive tract carcinogenesisHigh-risk individualsVivo chronic exposurePresence of bileSilent progressionTract cancerTobacco smokingInvasive carcinomaPremalignant lesions
2021
Targeting STAT3 prevents bile reflux‐induced oncogenic molecular events linked to hypopharyngeal carcinogenesis
Vageli DP, Doukas PG, Siametis A, Judson BL. Targeting STAT3 prevents bile reflux‐induced oncogenic molecular events linked to hypopharyngeal carcinogenesis. Journal Of Cellular And Molecular Medicine 2021, 26: 75-87. PMID: 34850540, PMCID: PMC8742186, DOI: 10.1111/jcmm.17011.Peer-Reviewed Original ResearchConceptsBcl-2 overexpressionTranscriptional activationTranscription factorsTranscriptional activitySignal transducerSTAT3 knockdownMolecular eventsCell survivalQPCR analysisLuciferase assaySTAT3 activationTargeting STAT3Oncogenic eventsAberrant activationHypopharyngeal carcinogenesisSTAT3 phosphorylationSTAT3Oncogenic effectsSTAT3 pathwayPharmacologic inhibitionPharmacological inhibitionSTA-21Hypopharyngeal cellsOncogenic profileWestern blotBile reflux and hypopharyngeal cancer
Vageli DP, Doukas SG, Doukas PG, Judson BL. Bile reflux and hypopharyngeal cancer. Oncology Reports 2021, 46: 244. PMID: 34558652, PMCID: PMC8485019, DOI: 10.3892/or.2021.8195.Peer-Reviewed Original ResearchConceptsHypopharyngeal cancerAcidic bileHypopharyngeal carcinogenesisBile refluxRisk factorsGastroesophageal reflux diseaseIndependent risk factorSquamous cell cancerUpper aerodigestive tractElevated p53 expressionAnti-apoptotic effectsReflux diseaseLaryngopharyngeal refluxAerodigestive tractCell cancerGastroesophageal refluxateContribution of STAT3Neck cancerPrecancerous lesionsPremalignant changesNeoplastic changesNF-κBDNA damageP53 expressionBile acidsPepsin Promotes Activation of Epidermal Growth Factor Receptor and Downstream Oncogenic Pathways, at Slightly Acidic and Neutral pH, in Exposed Hypopharyngeal Cells
Doukas PG, Vageli DP, Sasaki CT, Judson BL. Pepsin Promotes Activation of Epidermal Growth Factor Receptor and Downstream Oncogenic Pathways, at Slightly Acidic and Neutral pH, in Exposed Hypopharyngeal Cells. International Journal Of Molecular Sciences 2021, 22: 4275. PMID: 33924087, PMCID: PMC8074291, DOI: 10.3390/ijms22084275.Peer-Reviewed Original ResearchConceptsRelated-signaling pathwaysOncogenic pathwaysLaryngopharyngeal reflux diseaseEpidermal growth factor receptorSpecific oncogenic pathwaysDownstream oncogenic pathwaysGrowth factor receptorHypopharyngeal cellsReflux diseaseRisk factorsTherapeutic approachesIntermittent exposureTumorigenic effectsPronounced activationOncogenic factorSignificant upregulationFactor receptorSTAT3 activationAcidic pepsinEGFR activationCell viabilityPromotes ActivationActivationPrimary cellsCells
2020
The in vivo preventive and therapeutic properties of curcumin in bile reflux‐related oncogenesis of the hypopharynx
Doukas SG, Doukas PG, Sasaki CT, Vageli D. The in vivo preventive and therapeutic properties of curcumin in bile reflux‐related oncogenesis of the hypopharynx. Journal Of Cellular And Molecular Medicine 2020, 24: 10311-10321. PMID: 32691972, PMCID: PMC7521262, DOI: 10.1111/jcmm.15640.Peer-Reviewed Original ResearchConceptsNF-κBRecent pre-clinical studiesHuman hypopharyngeal cellsIndependent risk factorPre-clinical studiesNF-κB activationTherapeutic propertiesHypopharyngeal cellsRisk factorsMolecular eventsHypopharyngeal mucosaBile exposureImmunohistochemical analysisFuture translational developmentBile acidsOncogenic profileHypopharynxCarcinogenic effectsOncogenic functionOverexpression of RelAEpithelial cellsBileTranslational developmentExpression of genesCurcumin
2019
Biliary reflux as a causal factor in hypopharyngeal carcinoma: New clinical evidence and implications
Sasaki CT, Doukas SG, Costa J, Vageli DP. Biliary reflux as a causal factor in hypopharyngeal carcinoma: New clinical evidence and implications. Cancer 2019, 125: 3554-3565. PMID: 31310330, DOI: 10.1002/cncr.32369.Peer-Reviewed Original ResearchConceptsHuman hypopharyngeal squamous cell carcinomaAdjacent normal tissuesIL-6Reflux diseaseHypopharyngeal squamous cell carcinomaMiR-375Respective adjacent normal tissuesMiR-21Pilot studyEsophageal reflux diseaseIndependent risk factorNew clinical evidenceSquamous cell carcinomaOncomiR miR-21NF-κB activationMiR-21/miRTumor suppressor miR-375Quantitative polymerase chain reactionMessenger RNABiliary refluxHypopharyngeal carcinogenesisControl patientsLaryngopharyngeal refluxClinical evidenceHypopharyngeal carcinoma
2016
Gastro-duodenal fluid induced nuclear factor- κappa B activation and early pre-malignant alterations in murine hypopharyngeal mucosa
Vageli DP, Prasad ML, Sasaki CT. Gastro-duodenal fluid induced nuclear factor- κappa B activation and early pre-malignant alterations in murine hypopharyngeal mucosa. Oncotarget 2016, 7: 5892-5908. PMID: 26745676, PMCID: PMC4868729, DOI: 10.18632/oncotarget.6824.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Acids and SaltsBlotting, WesternCells, CulturedDuodenumFluorescent Antibody TechniqueHumansHypopharyngeal NeoplasmsHypopharynxImmunoenzyme TechniquesMiceMice, Inbred C57BLMucous MembraneNF-kappa BPrecancerous ConditionsReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionRNA, MessengerStomachConceptsHypopharyngeal mucosaNF-κB activationVivo modelSignificant NF-κB activationNF-κB pathwayCell proliferation markersΒ-catenin expressionC57BL/6J miceRisk factorsHistologic lesionsCell adhesion moleculeNF-κBVivo effectsProliferation markersP-STAT3B activationAdhesion moleculesNormal keratinocytesOncogenic pathwaysSTAT3 activationΒ-cateninBcl-2E-cadherinKi67Mucosa