2018
A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent
Thakar M, Hu Y, Morreale M, Lerner L, Lin W, Sen R, Cai Y, Karunasena E, Thakar M, Saggi S, Keer H, Ahuja N. A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent. PLOS ONE 2018, 13: e0199130. PMID: 29927979, PMCID: PMC6013229, DOI: 10.1371/journal.pone.0199130.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaDNA methyltransferase 1Chemotherapeutic agent irinotecanEpigenetic modulating agentsPDAC cell linesCell viabilityMechanism of actionSystemic chemotherapyCancer mortalityChemotherapy responseDuctal adenocarcinomaChemotherapy agentsEpigenetic sensitizationModulating agentsGuadecitabineAdditional studiesPancreatic cellsSerial concentrationsRest periodCell linesNanomolar concentrationsImproved responseEpigenetic modulatorsSensitizationMethyltransferase 1Treatment with epigenetic agents profoundly inhibits tumor growth in leiomyosarcoma
De Carvalho Fischer C, Hu Y, Morreale M, Lin WY, Wali A, Thakar M, Karunasena E, Sen R, Cai Y, Murphy L, Zahnow CA, Keer H, Thakar M, Ahuja N. Treatment with epigenetic agents profoundly inhibits tumor growth in leiomyosarcoma. Oncotarget 2018, 9: 19379-19395. PMID: 29721210, PMCID: PMC5922404, DOI: 10.18632/oncotarget.25056.Peer-Reviewed Original ResearchDNA methyltransferase inhibitorEpigenetic modulatorsLMS cell linesCell linesMES-SAApoptotic pathwayCell cycleMethyltransferase inhibitorCell survivalDifferentiation patternsEpigenetic agentsNovel chemotherapeutic regimensPotential therapeutic applicationsLeiomyosarcoma cell lineRare mesenchymal neoplasmSpectrum of sensitivityChemotherapeutic regimensPoor prognosisMesenchymal neoplasmsSensitive linesTumor growthGuadecitabineTherapeutic applicationsAdditional studiesModulator
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 assayChemotherapyEpigenetically altered miR-1247 functions as a tumor suppressor in pancreatic cancer
Yi JM, Kang EJ, Kwon HM, Bae JH, Kang K, Ahuja N, Yang K. Epigenetically altered miR-1247 functions as a tumor suppressor in pancreatic cancer. Oncotarget 2017, 5: 26600-26612. PMID: 28460450, PMCID: PMC5432282, DOI: 10.18632/oncotarget.15722.Peer-Reviewed Original ResearchConceptsCpG island hypermethylationTumor suppressorEctopic expressionPancreatic cancer cellsIsland hypermethylationPancreatic cancer cell linesHuman cancersPutative target genesCancer cell linesNumber of miRNAsChromosome condensation 2Role of miRNAsCell linesMolecular functional roleCancer cellsCpG island methylationPotential tumor suppressorTarget genesEpigenetic alterationsGene expressionMalignant human cancersIsland methylationDirect targetLuciferase reporterFunctional roleDifferential expression of hENT1 and hENT2 in colon cancer cell lines
Liu Y, Zuo T, Zhu X, Ahuja N, Fu T. Differential expression of hENT1 and hENT2 in colon cancer cell lines. Genetics And Molecular Research 2017, 16 PMID: 28218790, DOI: 10.4238/gmr16019549.Peer-Reviewed Original ResearchConceptsColon cancer cell linesCancer cell linesMetastatic CRCColorectal cancerHENT1 expressionCell linesHigh hENT1 expressionLow hENT1 expressionMetastatic colorectal cancerNucleoside analoguesHuman equilibrative nucleoside transporter 1Equilibrative nucleoside transporter 1Real-time polymerase chain reactionDrug-based treatmentQuantitative real-time polymerase chain reactionHuman colon cancer cell linesNucleoside transporter 1Clinical responseMost patientsMetastatic cell linesMetastatic sitesMetastatic tumorsTransporter expression profilesPolymerase chain reactionDifferent drug responses
2014
Functional Identification of Cancer-Specific Methylation of CDO1, HOXA9, and TAC1 for the Diagnosis of Lung Cancer
Wrangle J, Machida EO, Danilova L, Hulbert A, Franco N, Zhang W, Glöckner SC, Tessema M, Van Neste L, Easwaran H, Schuebel KE, Licchesi J, Hooker CM, Ahuja N, Amano J, Belinsky SA, Baylin SB, Herman JG, Brock MV. Functional Identification of Cancer-Specific Methylation of CDO1, HOXA9, and TAC1 for the Diagnosis of Lung Cancer. Clinical Cancer Research 2014, 20: 1856-1864. PMID: 24486589, PMCID: PMC4019442, DOI: 10.1158/1078-0432.ccr-13-2109.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerThree-gene panelLung cancerIndependent cohortPrimary NSCLC samplesCell lung cancerNSCLC cell linesNovel diagnostic biomarkersAdjuvant chemotherapyMolecular diagnostic testsCancer Genome AtlasCancer mortalityCancer-specific methylationSurgical specimensNSCLC samplesMolecular stagingEarly diagnosisDiagnostic biomarkersNormal tissuesDiagnostic testsCohortCancerGenome AtlasMethylation biomarkersCell lines
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
DNA methylation biomarker candidates for early detection of colon cancer
Yi JM, Dhir M, Guzzetta AA, Iacobuzio-Donahue CA, Heo K, Yang KM, Suzuki H, Toyota M, Kim HM, Ahuja N. DNA methylation biomarker candidates for early detection of colon cancer. Tumor Biology 2012, 33: 363-372. PMID: 22238052, PMCID: PMC3593674, DOI: 10.1007/s13277-011-0302-2.Peer-Reviewed Original ResearchConceptsPromoter DNA hypermethylationCpG island hypermethylationDNA hypermethylationColon cancer cell linesCancer cell linesGene expressionIsland hypermethylationCell linesDNA microarray approachEpigenetic therapeutic targetsGenome-wide platformsPromoter CpG island hypermethylationCancer-specific methylationTumor suppressor geneCancer-specific eventBisulfite sequencingCpG islandsTCERG1LMicroarray approachPromoter regionSuppressor geneGenesColorectal cancer cell linesHuman cancersCommon hallmark
2009
Prognostic Significance of Gremlin1 (GREM1) Promoter CpG Island Hypermethylation in Clear Cell Renal Cell Carcinoma
van Vlodrop IJ, Baldewijns MM, Smits KM, Schouten LJ, van Neste L, van Criekinge W, van Poppel H, Lerut E, Schuebel KE, Ahuja N, Herman JG, de Bruïne AP, van Engeland M. Prognostic Significance of Gremlin1 (GREM1) Promoter CpG Island Hypermethylation in Clear Cell Renal Cell Carcinoma. American Journal Of Pathology 2009, 176: 575-584. PMID: 20042676, PMCID: PMC2808066, DOI: 10.2353/ajpath.2010.090442.Peer-Reviewed Original ResearchConceptsClear cell renal cell carcinomaCell renal cell carcinomaRenal cell carcinomaCcRCC cell linesCell carcinomaIndependent patient seriesSignificant worse survivalMean vessel densityCell linesOverall survivalWorse survivalClinical outcomesPatient seriesTumor characteristicsPrognostic significanceTumor sizeBone morphogenetic protein antagonistFuhrman gradeMethylation-specific PCRUnivariate analysisVessel densityAngiogenic parametersMultivariate analysisActive angiogenesisTumor angiogenesis
2008
Convergence of Mutation and Epigenetic Alterations Identifies Common Genes in Cancer That Predict for Poor Prognosis
Chan TA, Glockner S, Yi JM, Chen W, Van Neste L, Cope L, Herman JG, Velculescu V, Schuebel KE, Ahuja N, Baylin SB. Convergence of Mutation and Epigenetic Alterations Identifies Common Genes in Cancer That Predict for Poor Prognosis. PLOS Medicine 2008, 5: e114. PMID: 18507500, PMCID: PMC2429944, DOI: 10.1371/journal.pmed.0050114.Peer-Reviewed Original ResearchConceptsTumor suppressor geneUnbiased genome-wide approachSuppressor geneGenome-wide approachesKey tumor suppressor genesBreast cancer cell linesSet of genesCancer cell linesLarge-scale sequencingTumor suppressor statusPromoter CpG island hypermethylationCell linesCpG island hypermethylationTumor-type specificRecent sequencingBiology of cancerEpigenetic eventsCancer genomesEpigenetic analysisEpigenetic alterationsCommon genesTumor suppressorSignificant genesGenetic changesIsland hypermethylationEpigenetic Inactivation of the Canonical Wnt Antagonist SRY-Box Containing Gene 17 in Colorectal Cancer
Zhang W, Glöckner S, Guo M, Machida EO, Wang DH, Easwaran H, Van Neste L, Herman JG, Schuebel KE, Watkins DN, Ahuja N, Baylin SB. Epigenetic Inactivation of the Canonical Wnt Antagonist SRY-Box Containing Gene 17 in Colorectal Cancer. Cancer Research 2008, 68: 2764-2772. PMID: 18413743, PMCID: PMC2823123, DOI: 10.1158/0008-5472.can-07-6349.Peer-Reviewed Original ResearchConceptsGene 17T-cell factor-dependent transcriptionHigh-mobility group transcription factorsFactor-dependent transcriptionMethylation-dependent silencingRegulation of developmentOverexpression of Sox17Cell linesCpG island hypermethylationWnt pathway activityPrecursor cell functionRepression domainHMG boxTranscription factorsDeletion analysisCpG islandsGene silencingDNA hypermethylationGene expressionPromoter regionEpigenetic inactivationCanonical WntGenetic changesIsland hypermethylationSOX17
2007
Methylation-induced silencing of ASC/TMS1, a pro-apoptotic gene, is a late-stage event in colorectal cancer
Riojas MA, Guo M, Glöckner SC, Machida EO, Baylin SB, Ahuja N. Methylation-induced silencing of ASC/TMS1, a pro-apoptotic gene, is a late-stage event in colorectal cancer. Cancer Biology & Therapy 2007, 6: 1710-1716. PMID: 17986858, DOI: 10.4161/cbt.6.11.4829.Peer-Reviewed Original ResearchConceptsASC/TMS1Normal colorectal tissue samplesCRC cell linesColorectal tissue samplesColorectal cancerColorectal adenomasMethylation-specific PCRCell linesMRNA expressionPro-apoptotic genesPrimary colorectal cancer specimensStage 1 cancerStage 2 cancerStage 3 cancerRight-sided tumorsPrimary colorectal cancerStage 4 cancerColorectal cancer specimensTissue samplesColorectal cancer cell linesNormal colorectal tissuesUnmethylated cell linesDifferent human neoplasmsCancer cell linesLate-stage eventComparing the DNA Hypermethylome with Gene Mutations in Human Colorectal Cancer
Schuebel KE, Chen W, Cope L, Glöckner SC, Suzuki H, Yi JM, Chan TA, Van Neste L, Van Criekinge W, van den Bosch S, van Engeland M, Ting AH, Jair K, Yu W, Toyota M, Imai K, Ahuja N, Herman JG, Baylin SB. Comparing the DNA Hypermethylome with Gene Mutations in Human Colorectal Cancer. PLOS Genetics 2007, 3: e157. PMID: 17892325, PMCID: PMC1988850, DOI: 10.1371/journal.pgen.0030157.Peer-Reviewed Original ResearchConceptsTranscriptome-wide approachCpG island DNA hypermethylationHuman colorectal cancer samplesHuman cancer genomesTumor-specific hypermethylationEpigenetic screensTranscriptional silencingIndividual genesCancer genomesEpigenetic changesDNA hypermethylationGene mutationsGenesHypermethylationCell linesIndividual tumorsHuman colorectal cancerColorectal cancer samplesCancer samplesMutationsColorectal cancerCancer biomarkersGenomeSilencingPromoter
1999
CpG island methylator phenotype in colorectal cancer
Toyota M, Ahuja N, Ohe-Toyota M, Herman J, Baylin S, Issa J. CpG island methylator phenotype in colorectal cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 8681-8686. PMID: 10411935, PMCID: PMC17576, DOI: 10.1073/pnas.96.15.8681.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAge FactorsCarrier ProteinsCloning, MolecularColorectal NeoplasmsCpG IslandsDNA MethylationDNA RepairGenes, p16Genes, Tumor SuppressorHumansMicrosatellite RepeatsMutL Protein Homolog 1Neoplasm ProteinsNuclear ProteinsPhenotypePolymerase Chain ReactionSulfitesTumor Cells, CulturedConceptsCpG island methylator phenotypeColorectal cancerMethylator phenotypeSporadic colorectal cancerMismatch repair deficiencyCpG islandsAge-dependent mannerNormal colonic cellsCpG island amplificationHigh incidenceColon cancerTHBS1 methylationNormal colonPromoter region CpG islandsSporadic tumorsCancerMicrosatellite instabilityColonic cellsTumor suppressor geneCpG island methylationRepair deficiencyCancer-specific mannerHMLH1 methylationCell linesTranscriptional inactivationMethylation and silencing of the Thrombospondin-1 promoter in human cancer
Li Q, Ahuja N, Burger P, Issa J. Methylation and silencing of the Thrombospondin-1 promoter in human cancer. Oncogene 1999, 18: 3284-3289. PMID: 10359534, DOI: 10.1038/sj.onc.1202663.Peer-Reviewed Original ResearchConceptsGlioblastoma multiformeTHBS1 expressionThrombospondin-1De novo methylationHuman cancersCell linesPrimary glioblastoma multiformeMethylation-associated inactivationNovo methylationCpG islandsPrimary tumorCpG sitesAngiogenesis inhibitorsTHBS1 methylationMethylation statusMolecular defectsHuman neoplasmsMethylationHuman tumorsDetectable expressionCancerTumorsExpressionCommon featureSilencing
1998
Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma
Herman J, Umar A, Polyak K, Graff J, Ahuja N, Issa J, Markowitz S, Willson J, Hamilton S, Kinzler K, Kane M, Kolodner R, Vogelstein B, Kunkel T, Baylin S. Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 6870-6875. PMID: 9618505, PMCID: PMC22665, DOI: 10.1073/pnas.95.12.6870.Peer-Reviewed Original ResearchConceptsCpG islandsMismatch repair genesCell linesDNA mismatch repairMMR-deficient cell linesDNA methylationSuch methylationSporadic primary colorectal cancerEpigenetic inactivationMMR capacityMismatch repairRepair genesMethylationFunctional consequencesColorectal cancer cell linesCancer cell linesPromoter hypermethylationHypermethylationMicrosatellite instabilityProtein expressionHMLH1 proteinGenesColorectal cancerHMLH1 protein expressionInactivation