2020
Neoantigen-based EpiGVAX vaccine initiates antitumor immunity in colorectal cancer
Kim VM, Pan X, Soares KC, Azad NS, Ahuja N, Gamper CJ, Blair AB, Muth S, Ding D, Ladle BH, Zheng L. Neoantigen-based EpiGVAX vaccine initiates antitumor immunity in colorectal cancer. JCI Insight 2020, 5: e136368. PMID: 32376802, PMCID: PMC7253020, DOI: 10.1172/jci.insight.136368.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerColorectal cancerDNA methyltransferase inhibitorAntitumor efficacyAntigen-specific antitumor immune responsesAntitumor T-cell responsesCancer testis antigen expressionAntitumor immune responseT cell responsesAntitumor immunityCancer vaccinesSurvival outcomesCombination therapyAntigen expressionImmune responseMurine modelCTA expressionCell responsesNeoantigensImproved efficacyTumor cellsVaccineEfficacyGVAXMethyltransferase inhibitor
2018
DNA Methylation Patterns Separate Senescence from Transformation Potential and Indicate Cancer Risk
Xie W, Kagiampakis I, Pan L, Zhang YW, Murphy L, Tao Y, Kong X, Kang B, Xia L, Carvalho FLF, Sen S, Yen R, Zahnow CA, Ahuja N, Baylin SB, Easwaran H. DNA Methylation Patterns Separate Senescence from Transformation Potential and Indicate Cancer Risk. Cancer Cell 2018, 33: 309-321.e5. PMID: 29438699, PMCID: PMC5813821, DOI: 10.1016/j.ccell.2018.01.008.Peer-Reviewed Original ResearchConceptsDevelopmental genesDNA methylation patternsPromoter hypermethylation eventsEpigenetic patternsMethylation gainMethylation patternsMethylation changesHypermethylation eventsEpigenetic changesTissue agingSenescenceMetabolic regulatorTissue typesGenesTransformation potentialCellsHypermethylationRegulatorCancer risk
2017
Inhibiting DNA methylation activates cancer testis antigens and expression of the antigen processing and presentation machinery in colon and ovarian cancer cells
Siebenkäs C, Chiappinelli KB, Guzzetta AA, Sharma A, Jeschke J, Vatapalli R, Baylin SB, Ahuja N. Inhibiting DNA methylation activates cancer testis antigens and expression of the antigen processing and presentation machinery in colon and ovarian cancer cells. PLOS ONE 2017, 12: e0179501. PMID: 28622390, PMCID: PMC5473589, DOI: 10.1371/journal.pone.0179501.Peer-Reviewed Original ResearchConceptsSubset of patientsOvarian cancer cell linesAntigen processingCancer cell linesImmune therapyCancer testisSolid tumorsCell linesCancer cellsCancer-testis antigensHost immune systemOvarian cancer cellsTreatment time pointsEpigenetic therapyRelevant low dosesPresentation machineryImmune cellsOvarian cancerAntigen presentationMurine modelTestis antigensInnovative therapiesImmune systemLow dosesTherapyHypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells
Sharma A, Vatapalli R, Abdelfatah E, McMahon K, Kerner Z, Guzzetta A, Singh J, Zahnow C, Baylin S, Yerram S, Hu Y, Azad N, Ahuja N. Hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells. PLOS ONE 2017, 12: e0176139. PMID: 28445481, PMCID: PMC5405959, DOI: 10.1371/journal.pone.0176139.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsATP-Binding Cassette TransportersAzacitidineCaco-2 CellsCamptothecinCell AdhesionCell Line, TumorCell ProliferationColorectal NeoplasmsDNA MethylationDNA RepairGene ExpressionGene Expression ProfilingHCT116 CellsHumansIrinotecanLong Interspersed Nucleotide ElementsMiceMice, Inbred NODMice, SCIDConceptsCRC cell linesColorectal cancerMultiple CRC cell linesPhase 1/2 clinical trialCell linesMetastatic colorectal cancerMajority of patientsNOD-SCID miceColorectal cancer cellsSoft agar assayInitial therapyMetastatic settingCytotoxic chemotherapyCRC treatmentClinical efficacyCancer deathTumor regressionClinical trialsDNA demethylating agentVivo xenograftsChemotherapeutic agentsCancer cellsHCT116 cell linesAgar assayChemotherapy
2013
CHFR silencing or microsatellite instability is associated with increased antitumor activity of docetaxel or gemcitabine in colorectal cancer
Pelosof L, Yerram SR, Ahuja N, Delmas A, Danilova L, Herman JG, Azad NS. CHFR silencing or microsatellite instability is associated with increased antitumor activity of docetaxel or gemcitabine in colorectal cancer. International Journal Of Cancer 2013, 134: 596-605. PMID: 23873170, PMCID: PMC3830586, DOI: 10.1002/ijc.28390.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBase SequenceCell Cycle ProteinsCell Line, TumorColorectal NeoplasmsDeoxycytidineDNA MethylationDNA PrimersDocetaxelFemaleGemcitabineGene SilencingHumansMiceMicrosatellite InstabilityNeoplasm ProteinsPoly-ADP-Ribose Binding ProteinsPromoter Regions, GeneticReal-Time Polymerase Chain ReactionTaxoidsUbiquitin-Protein LigasesXenograft Model Antitumor AssaysConceptsTumor growth inhibitionColorectal cancerCombination therapyCHFR methylationCell linesAdditive tumor growth inhibitionBiomarker-selected patient populationsMicrosatellite instabilityGrowth inhibitionOngoing clinical trialsCRC cell linesCell line xenograftsMSI-H cell linesCRC patientsChemotherapy responsePatient populationPredictive markerClinical trialsDifferential sensitivityTherapeutic effectHuman xenograftsVivo treatmentMSI statusChemotherapy sensitivityGemcitabine
2012
Transient Low Doses of DNA-Demethylating Agents Exert Durable Antitumor Effects on Hematological and Epithelial Tumor Cells
Tsai HC, Li H, Van Neste L, Cai Y, Robert C, Rassool FV, Shin JJ, Harbom KM, Beaty R, Pappou E, Harris J, Yen RW, Ahuja N, Brock MV, Stearns V, Feller-Kopman D, Yarmus LB, Lin YC, Welm AL, Issa JP, Minn I, Matsui W, Jang YY, Sharkis SJ, Baylin SB, Zahnow CA. Transient Low Doses of DNA-Demethylating Agents Exert Durable Antitumor Effects on Hematological and Epithelial Tumor Cells. Cancer Cell 2012, 21: 430-446. PMID: 22439938, PMCID: PMC3312044, DOI: 10.1016/j.ccr.2011.12.029.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntimetabolites, AntineoplasticApoptosisAzacitidineBone Marrow CellsBreast NeoplasmsCell CycleCell Line, TumorCell Transformation, NeoplasticDecitabineDNA DamageDNA MethylationDNA Modification MethylasesGene SilencingHumansLeukemiaMiceMolecular Sequence DataNeoplastic Stem CellsPromoter Regions, GeneticSignal TransductionTumor Cells, CulturedConceptsKey cellular regulatory pathwaysDNA methylation inhibitorPromoter DNA hypermethylationCellular regulatory pathwaysDNA demethylating agentEpithelial tumor cellsPromoter DNA methylationRapid DNA damageCancer stem-like cellsGene reexpressionDNA methylationStem-like cellsMethylation inhibitorDNA hypermethylationRegulatory pathwaysCancer therapy approachesAssociated geneDNA damageTumor cellsImmediate cytotoxicityNanomolar dosesTransient exposureCellsGenesMethylation
2008
Abnormal DNA Methylation of CD133 in Colorectal and Glioblastoma Tumors
Yi JM, Tsai HC, Glöckner S, Lin S, Ohm JE, Easwaran H, James CD, Costello JF, Riggins G, Eberhart CG, Laterra J, Vescovi AL, Ahuja N, Herman JG, Schuebel KE, Baylin SB. Abnormal DNA Methylation of CD133 in Colorectal and Glioblastoma Tumors. Cancer Research 2008, 68: 8094-8103. PMID: 18829568, PMCID: PMC2744404, DOI: 10.1158/0008-5472.can-07-6208.Peer-Reviewed Original ResearchMeSH KeywordsAC133 AntigenAnimalsAntigens, CDAntineoplastic AgentsAzacitidineBrain NeoplasmsCaco-2 CellsCarcinomaColorectal NeoplasmsDecitabineDNA (Cytosine-5-)-MethyltransferasesDNA MethylationFemaleGene DeletionGene Expression Regulation, NeoplasticGlioblastomaGlycoproteinsHCT116 CellsHT29 CellsHumansMiceMice, NudePeptidesTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsDNA methylationMethylation patternsPromoter DNA methylation patternsHistone modification marksDNA methylation patternsDNA methylation changesDNA methylation statusPromoter CpG islandsAberrant DNA methylationAbnormal DNA methylationCultured colon cancerStem-like cell populationTranscription stateModification marksPromoter signaturesCpG islandsSuch methylationIndividual cell linesMethylation changesAberrant genesDifferentiated progenyMethylationMarker proteinsMethylation statusGenes