2020
Exposing Hidden Targets: Combining epigenetic and immunotherapy to overcome cancer resistance
Olino K, Park T, Ahuja N. Exposing Hidden Targets: Combining epigenetic and immunotherapy to overcome cancer resistance. Seminars In Cancer Biology 2020, 65: 114-122. PMID: 31911188, DOI: 10.1016/j.semcancer.2020.01.001.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsResponse ratePeripheral T-cell lymphomaTriple-negative breast cancerLarge B-cell lymphomaDurable response rateEffective standard therapyDeath protein 1Solid organ tumorsInhibitory immune receptorsT-cell lymphomaNegative breast cancerB-cell lymphomaAdvanced malignanciesMost patientsStandard therapyClinical efficacyCommon malignancyHepatobiliary cancersTherapeutic optionsNeck cancerOrgan tumorsInitial respondersOvarian cancerProstate cancerBreast cancer
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 1
2017
Hypomethylating 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
2016
Methylation of MGMT Is Associated with Poor Prognosis in Patients with Stage III Duodenal Adenocarcinoma
Fu T, Sharmab A, Xie F, Liu Y, Li K, Wan W, Baylin SB, Wolfgang CL, Ahuja N. Methylation of MGMT Is Associated with Poor Prognosis in Patients with Stage III Duodenal Adenocarcinoma. PLOS ONE 2016, 11: e0162929. PMID: 27643594, PMCID: PMC5028050, DOI: 10.1371/journal.pone.0162929.Peer-Reviewed Original ResearchConceptsDisease-free survivalCpG island methylator phenotypeDuodenal adenocarcinomaOverall survivalMethylation of MGMTMGMT methylationMicrosatellite instabilityPoor prognosisKRAS mutationsCox proportional hazards modelMGMT unmethylated groupTumor molecular featuresChemotherapy/radiotherapyIndependent prognostic factorO6-methylguanine-DNA methyltransferase methylation statusWorse overall survivalPossible prognostic valueProportional hazards modelMGMT methylation statusPrognostic factorsClinicopathological characteristicsTumor characteristicsMethylation statusPrognostic valueTumor differentiationLong‐term outcomes in treatment of retroperitoneal sarcomas: A 15 year single‐institution evaluation of prognostic features
Abdelfatah E, Guzzetta AA, Nagarajan N, Wolfgang CL, Pawlik TM, Choti MA, Schulick R, Montgomery EA, Meyer C, Thornton K, Herman J, Terezakis S, Frassica D, Ahuja N. Long‐term outcomes in treatment of retroperitoneal sarcomas: A 15 year single‐institution evaluation of prognostic features. Journal Of Surgical Oncology 2016, 114: 56-64. PMID: 27076350, PMCID: PMC4917421, DOI: 10.1002/jso.24256.Peer-Reviewed Original ResearchConceptsCompartmental resectionRPS patientsSurgical resectionPrognostic factorsR0/R1 marginsR0/R1 resectionEn bloc surgical resectionBloc surgical resectionCornerstone of therapyMainstay of treatmentFive-year survivalRetrospective chart reviewPresence of metastasesEn bloc resectionExtent of resectionConnective tissue tumorsJohns Hopkins HospitalWarrants further investigationR1 resectionRetroperitoneal sarcomaChart reviewMedian survivalR1 marginsDistal recurrenceLocal recurrence
2015
Time to Chemotherapy After Abdominoperineal Resection: Comparison Between Primary Closure and Perineal Flap Reconstruction
Althumairi AA, Canner JK, Ahuja N, Sacks JM, Safar B, Efron JE. Time to Chemotherapy After Abdominoperineal Resection: Comparison Between Primary Closure and Perineal Flap Reconstruction. World Journal Of Surgery 2015, 40: 225-230. PMID: 26336877, DOI: 10.1007/s00268-015-3224-0.Peer-Reviewed Original ResearchConceptsFlap reconstruction groupAdjuvant chemotherapyFlap reconstructionPrimary closureAbdominoperineal resectionWound complicationsRectal adenocarcinomaReconstruction groupWound healingPerineal flap reconstructionPerineal wound complicationsPrimary closure groupPerineal wound closureLength of healingRetrospective reviewClosure groupChemotherapyPatientsPerineal defectsWound closureHealingResectionComplicationsAdenocarcinomaLength of timeEpigenetic therapy for solid tumors: from bench science to clinical trials
Juo YY, Gong XJ, Mishra A, Cui X, Baylin SB, Azad NS, Ahuja N. Epigenetic therapy for solid tumors: from bench science to clinical trials. Epigenomics 2015, 7: 215-235. PMID: 25942532, DOI: 10.2217/epi.14.73.Peer-Reviewed Original ResearchConceptsEpigenetic agentsCpG island promotersSolid tumorsGlobal DNA methylationOptimal patient selectionTumor suppressor geneNew therapeutic modalitiesChromatin changesCancer epigenomeHistone deacetylase inhibitorsDNA methylationDNA methyltransferaseEpigenetic therapyHormonal therapyDrug regimenSuppressor genePatient selectionFuture trialsHematologic malignanciesRecent trialsClinical trialsSignificant efficacyTherapeutic modalitiesPhenotype changesDeacetylase inhibitors
2014
Clinicopathologic Presentation and Natural History of Anorectal Melanoma: A Case Series of 18 Patients
Hicks CW, Pappou EP, Magruder JT, Gazer B, Fang S, Wick EC, Gearhart SL, Ahuja N, Efron JE. Clinicopathologic Presentation and Natural History of Anorectal Melanoma: A Case Series of 18 Patients. JAMA Surgery 2014, 149: 608-611. PMID: 24848283, DOI: 10.1001/jamasurg.2013.4643.Peer-Reviewed Original ResearchConceptsAnorectal melanomaOverall disease-specific mortalityNatural historyDisease-specific mortalityDisease-specific survivalNonspecific presenting symptomsWide local excisionRare malignant neoplasmVariable natural historyNonspecific presentationPresenting symptomAbdominoperineal resectionLocal excisionCase seriesMedian timeSurgical managementRectal lesionsMalignant neoplasmsPrognostic parametersClinicopathologic presentationLate diagnosisAdvanced stageIncorrect diagnosisSmall lesionsLarger studyHarnessing the potential of epigenetic therapy to target solid tumors
Ahuja N, Easwaran H, Baylin SB. Harnessing the potential of epigenetic therapy to target solid tumors. Journal Of Clinical Investigation 2014, 124: 56-63. PMID: 24382390, PMCID: PMC3871229, DOI: 10.1172/jci69736.Peer-Reviewed Original Research
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
The Heat of the Matter: Comment on “Initial Experience With Hyperthermic Intraperitoneal Chemotherapy”
Ahuja N. The Heat of the Matter: Comment on “Initial Experience With Hyperthermic Intraperitoneal Chemotherapy”. JAMA Surgery 2012, 147: 924-924. PMID: 23117831, DOI: 10.1001/archsurg.2012.1292.Peer-Reviewed Original Research
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