2023
A study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer
Baretti M, Murphy A, Zahurak M, Gianino N, Parkinson R, Walker R, Lopez-Vidal T, Zheng L, Rosner G, Ahuja N, Kurt S, Azad N. A study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer. Clinical Epigenetics 2023, 15: 74. PMID: 37120591, PMCID: PMC10149019, DOI: 10.1186/s13148-023-01485-x.Peer-Reviewed Original ResearchConceptsColorectal cancer patientsAdvanced colorectal cancer patientsImmune checkpoint inhibitor therapyMedian progression-free survivalDurable partial responseHematological adverse eventsMMR-proficient tumorsCheckpoint inhibitor therapyAdvanced colorectal cancerProgression-free survivalImmune cell infiltrationHistone deacetylasesImmunologic shiftCheckpoint inhibitorsRECIST criteriaAdverse eventsCheckpoint therapyOverall survivalPartial responseInhibitor therapyMedian ageColorectal cancerFurther mechanistic investigationsCancer patientsCell infiltration
2022
Bile acid distributions, sex-specificity, and prognosis in colorectal cancer
Cai Y, Shen X, Lu L, Yan H, Huang H, Gaule P, Muca E, Theriot CM, Rattray Z, Rattray NJW, Lu J, Ahuja N, Zhang Y, Paty PB, Khan SA, Johnson CH. Bile acid distributions, sex-specificity, and prognosis in colorectal cancer. Biology Of Sex Differences 2022, 13: 61. PMID: 36274154, PMCID: PMC9590160, DOI: 10.1186/s13293-022-00473-9.Peer-Reviewed Original ResearchConceptsLeft-sided colon tumorsRight-sided colon tumorsColon cancer patientsColorectal cancerTumor locationBile acidsColon tumorsCancer patientsQuantitative immunofluorescencePrimary tumor locationImmune regulatory cellsRecurrence-free survivalBile acid metabolismSecondary bile acidsBile acid distributionBile acid analysisBackgroundBile acidsOverall survivalRegulatory cellsCRC patientsMale patientsPatient sexImmune cellsPatient prognosisImmune response1147: DISPARITIES IN TIME TO TREATMENT INITIATION IN COLORECTAL CANCER IN THE US FROM 2004-2018: ANALYSIS OF THE NATIONAL CANCER DATABASE
Khatri R, Chhoda A, Sharma A, Farrell J, Ahuja N, Ehrlich A, Friedenberg F. 1147: DISPARITIES IN TIME TO TREATMENT INITIATION IN COLORECTAL CANCER IN THE US FROM 2004-2018: ANALYSIS OF THE NATIONAL CANCER DATABASE. Gastroenterology 2022, 162: s-270-s-271. DOI: 10.1016/s0016-5085(22)60641-3.Peer-Reviewed Original Research
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
2019
MAPT promoter CpG island hypermethylation is associated with poor prognosis in patients with stage II colorectal cancer
Wang C, Liu Y, Guo W, Zhu X, Ahuja N, Fu T. MAPT promoter CpG island hypermethylation is associated with poor prognosis in patients with stage II colorectal cancer. Cancer Management And Research 2019, 11: 7337-7343. PMID: 31496795, PMCID: PMC6689138, DOI: 10.2147/cmar.s206731.Peer-Reviewed Original ResearchStage II colorectal cancerColorectal cancerFive-year overall survival rateStage II CRC patientsOverall survival rateCox regression analysisImportant prognostic variablesProximal colon tumorsCpG island methylator phenotype (CIMP) statusMicrotubule-associated protein tauCIMP-high tumorsPromoter CpG islandsCRC patientsWorse prognosisPoor prognosisPrognostic valuePrognostic markerPrognostic variablesPatientsHigh tumorSurvival rateAlzheimer's diseaseColon tumorsMultivariate analysisProtein tauEpigenetic priming prior to pembrolizumab in mismatch repair-proficient advanced colorectal cancer.
Murphy A, Walker R, Lutz E, Parkinson R, Ahuja N, Zheng L, Jaffee E, Azad N. Epigenetic priming prior to pembrolizumab in mismatch repair-proficient advanced colorectal cancer. Journal Of Clinical Oncology 2019, 37: 591-591. DOI: 10.1200/jco.2019.37.4_suppl.591.Peer-Reviewed Original ResearchArm BArm AColorectal cancerAdvanced CRC patientsMedian treatment cycleMMR-deficient CRCMMR-proficient tumorsLines of chemotherapyAdvanced colorectal cancerPre-treatment biopsiesPost-treatment biopsiesPredictors of responseEpigenetic therapyCTCAE v4.0CRC patientsImmune checkpointsMedian ageProficient tumorsRepeat biopsySingle institutionDisease progressionArm C.Arm CGrade 3Patients
2018
A Phase I Trial of a Guadecitabine (SGI-110) and Irinotecan in Metastatic Colorectal Cancer Patients Previously Exposed to Irinotecan
Lee V, Wang J, Zahurak M, Gootjes E, Verheul H, Parkinson R, Kerner Z, Sharma A, Rosner G, De Jesus-Acosta A, Laheru D, Le DT, Oganesian A, Lilly E, Brown T, Jones P, Baylin S, Ahuja N, Azad N. A Phase I Trial of a Guadecitabine (SGI-110) and Irinotecan in Metastatic Colorectal Cancer Patients Previously Exposed to Irinotecan. Clinical Cancer Research 2018, 24: 6160-6167. PMID: 30097434, DOI: 10.1158/1078-0432.ccr-18-0421.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerNeutropenic feverMetastatic colorectal cancer patientsDurable partial responseMost common toxicitiesDose-escalation studyColorectal cancer patientsInjection site reactionsOngoing phase IIPhase I trialInitial disease progressionCycles of treatmentCommon toxicitiesDrain infectionEvaluable patientsStable diseaseColonic obstructionPartial responseI trialMulticenter trialColorectal cancerGastrointestinal cancerSite reactionsCancer patientsDisease progressionAutomated diagnosis of colon cancer using hyperspectral sensing
Beaulieu RJ, Goldstein SD, Singh J, Safar B, Banerjee A, Ahuja N. Automated diagnosis of colon cancer using hyperspectral sensing. International Journal Of Medical Robotics And Computer Assisted Surgery 2018, 14: e1897. PMID: 29479794, DOI: 10.1002/rcs.1897.Peer-Reviewed Original ResearchConceptsColorectal cancerPossible metastatic diseaseColorectal cancer detectionColorectal cancer reliesMultiple tumor typesMetastatic diseaseOperative resectionSurgical resectionPathologic evaluationSurgical managementCancer reliesTumor specimensColon specimensColon cancerTumor typesPatient specimensCancerResectionPatientsDiagnostic methodsTumorsCancer detectionDiagnostic technologiesContrast agents
2017
Genomics of peritoneal surface malignancies
Singh J, Sharma A, Ahuja N. Genomics of peritoneal surface malignancies. Journal Of Peritoneum (and Other Serosal Surfaces) 2017, 2 DOI: 10.4081/joper.2017.62.Peer-Reviewed Original ResearchPeritoneal malignancyHyperthermic intraperitoneal chemotherapyPeritoneal surface malignanciesLong-term survivalPrediction of responseAppendiceal neoplasmsIntraperitoneal chemotherapySurface malignanciesPeritoneal mesotheliomaPeritoneal metastasisPseudomyxoma peritoneiAggressive cytoreductionColorectal cancerTargeted therapyTerminal diseaseTherapeutic markersClinical decisionMalignancyClinical therapyTherapyGenomic alterationsMetastasisGenomic anomaliesGenomic characterizationCytoreductionHypomethylating 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 assayChemotherapyCombination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat; a phase 2 consortium/stand Up 2 cancer study
Azad NS, el-Khoueiry A, Yin J, Oberg AL, Flynn P, Adkins D, Sharma A, Weisenberger DJ, Brown T, Medvari P, Jones PA, Easwaran H, Kamel I, Bahary N, Kim G, Picus J, Pitot HC, Erlichman C, Donehower R, Shen H, Laird PW, Piekarz R, Baylin S, Ahuja N. Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat; a phase 2 consortium/stand Up 2 cancer study. Oncotarget 2017, 5: 35326-35338. PMID: 28186961, PMCID: PMC5471058, DOI: 10.18632/oncotarget.15108.Peer-Reviewed Original ResearchConceptsCombination epigenetic therapyMetastatic colorectal cancerRECIST responseCRC patientsMedian progression-free survivalCycles of therapySignificant clinical activityMetastatic CRC patientsProgression-free survivalSubset of patientsM2 days 1Serial tumor biopsiesMulti-institutional studyHistone deacetylase inhibitor entinostatEpigenetic therapyColorectal cell linesSubcutaneous azacitidinePrimary endpointPrior therapyLiver involvementOverall survivalTolerable therapySerial biopsiesColorectal cancerClinical activityDifferential 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
2016
Locally advanced primary recto-sigmoid cancers: Improved survival with multivisceral resection
Laurence G, Ahuja V, Bell T, Grim R, Ahuja N. Locally advanced primary recto-sigmoid cancers: Improved survival with multivisceral resection. The American Journal Of Surgery 2016, 214: 432-436. PMID: 28082009, DOI: 10.1016/j.amjsurg.2016.12.018.Peer-Reviewed Original ResearchConceptsMultivisceral resectionAdvanced colorectal cancerColorectal cancerCancer patientsYear survivalNon-metastatic colorectal cancerRadiation treatmentRecto-sigmoid cancerFive-year survivalSignificant associated morbidityKaplan-Meier analysisExtensive surgical proceduresGreatest survival advantageEligible patientsAssociated morbiditySelect patientsMeier analysisStandard surgeryRadical operationSEER dataAdjacent organsSurgical proceduresSurvival advantagePatientsSurgical specialistsO1-10-3 Associations of IGFBP3 SNPs, methylation and recurrence risk in patients with stage II colorectal cancer
Fu T, Li F, Ye J, Liu Z, Wolfgang C, Iacobuzio-Donahue C, Tong W, Liu B, Ahuja N. O1-10-3 Associations of IGFBP3 SNPs, methylation and recurrence risk in patients with stage II colorectal cancer. Annals Of Oncology 2016, 27: vii78. DOI: 10.1093/annonc/mdw521.016.Peer-Reviewed Original ResearchPassive Hyperspectral Sensing Reliably Identifies Colorectal Cancer in Intraoperative Colon Specimens
Beaulieu R, Goldstein S, Banerjee A, Safar B, Ahuja N. Passive Hyperspectral Sensing Reliably Identifies Colorectal Cancer in Intraoperative Colon Specimens. Journal Of The American College Of Surgeons 2016, 223: s34. DOI: 10.1016/j.jamcollsurg.2016.06.087.Peer-Reviewed Original ResearchColorectal cancerColon specimensIGFBP-3 Gene Methylation in Primary Tumor Predicts Recurrence of Stage II Colorectal Cancers
Fu T, Pappou EP, Guzzetta AA, de Freitas Calmon M, Sun L, Herrera A, Li F, Wolfgang CL, Baylin SB, Iacobuzio-Donahue CA, Tong W, Ahuja N. IGFBP-3 Gene Methylation in Primary Tumor Predicts Recurrence of Stage II Colorectal Cancers. Annals Of Surgery 2016, 263: 337-344. PMID: 25822686, PMCID: PMC4648704, DOI: 10.1097/sla.0000000000001204.Peer-Reviewed Original ResearchConceptsStage II colorectal cancerRisk of recurrenceIGFBP-3 methylationLymph nodesColorectal cancerHazard ratioPrimary tumorHigh riskIndependent cohortFive-year recurrence-free survival ratesRecurrence-free survival ratesHigh-risk patientsSignificant prognostic factorsIdentification of patientsProportional hazards modelIGFBP-3Prognostic factorsTumor characteristicsPredicts RecurrenceHazards modelPatientsRecurrenceSurvival rateMultivariate analysisSurgery
2015
A phase I study of investigational agent SGI-110 combined with irinotecan in previously treated metastatic colorectal cancer patients.
Wang J, Gootjes E, Uram J, Zahurak M, El-Khoueiry A, Verheul H, Ahuja N, Azad N. A phase I study of investigational agent SGI-110 combined with irinotecan in previously treated metastatic colorectal cancer patients. Journal Of Clinical Oncology 2015, 33: tps797-tps797. DOI: 10.1200/jco.2015.33.3_suppl.tps797.Peer-Reviewed Original ResearchDose level 1SGI-110Colorectal cancerPhase ITumor biopsiesDay 1Metastatic colorectal cancer patientsRandomized phase II studyMajor eligibility criteriaPeriodic CT scansPhase II studyGrowth factor supportColorectal cancer patientsM2 days 1Metastatic colon adenocarcinomaMetastatic colon cancerCRC cell linesAdditional dose levelsEvaluation of biomarkersMeasureable diseaseTotal therapyII studyIrinotecan therapyDose escalationFactor support
2014
CpG island methylator phenotype and its association with malignancy in sporadic duodenal adenomas
Sun L, Guzzetta AA, Fu T, Chen J, Jeschke J, Kwak R, Vatapalli R, Baylin SB, Iacobuzio-Donahue CA, Wolfgang CL, Ahuja N. CpG island methylator phenotype and its association with malignancy in sporadic duodenal adenomas. Epigenetics 2014, 9: 738-746. PMID: 24518818, PMCID: PMC4063833, DOI: 10.4161/epi.28082.Peer-Reviewed Original ResearchConceptsCpG island methylator phenotypeSporadic duodenal adenomasDuodenal adenomasBRAF mutationsVillous typeMethylator phenotypeCIMP-high statusPeriampullary locationAggressive managementDuodenal adenocarcinomaClinicopathologic featuresColorectal cancerColorectal adenomasKRAS mutationsHigh riskAdenomasMLH1 methylationCIMP statusCancerous lesionsOlder ageP16 methylationTumorsMalignancyInfrequent eventRole of methylation
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 sensitivityGemcitabineThe CpG Island Methylator Phenotype: What's in a Name?
Hughes LA, Melotte V, de Schrijver J, de Maat M, Smit VT, Bovée JV, French PJ, van den Brandt PA, Schouten LJ, de Meyer T, van Criekinge W, Ahuja N, Herman JG, Weijenberg MP, van Engeland M. The CpG Island Methylator Phenotype: What's in a Name? Cancer Research 2013, 73: 5858-5868. PMID: 23801749, DOI: 10.1158/0008-5472.can-12-4306.Peer-Reviewed Original ResearchConceptsCpG island methylator phenotypeTranslocation methylcytosine dioxygenase 2Tumor typesMethylator phenotypePrimary human astrocytesHuman neoplasiaIsocitrate dehydrogenase 1 (IDH1) mutationCpG island promoter methylationColorectal cancerOllier's diseaseAdrenocortical carcinomaProstate cancerMultiple enchondromasHuman astrocytesClinical practiceRenal cellsIDH2 mutationsCancer typesCancerDioxygenase 2Promoter methylationFunction mutationsMafucci's syndromeNeoplasiaLeukemia