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 response
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
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 ResearchMeSH KeywordsAdultAgedAged, 80 and overColorectal NeoplasmsFemaleHumansMaleMiddle AgedProspective StudiesROC CurveSensitivity and SpecificitySpectrum AnalysisConceptsColorectal 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
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 assayChemotherapyPostoperative complications following intraoperative radiotherapy in abdominopelvic malignancy: A single institution analysis of 113 consecutive patients
Abdelfatah E, Page A, Sacks J, Pierorazio P, Bivalacqua T, Efron J, Terezakis S, Gearhart S, Fang S, Safar B, Pawlik TM, Armour E, Hacker‐Prietz A, Herman J, Ahuja N. Postoperative complications following intraoperative radiotherapy in abdominopelvic malignancy: A single institution analysis of 113 consecutive patients. Journal Of Surgical Oncology 2017, 115: 883-890. PMID: 28252805, PMCID: PMC5572190, DOI: 10.1002/jso.24597.Peer-Reviewed Original ResearchConceptsExternal beam radiation therapyPostoperative complication rateIntraoperative radiotherapyComplication rateInstitution experienceGrade IIAcceptable perioperative morbidityComplications grade IICurative-intent resectionPostoperative surgical complicationsClavien-Dindo scaleMost common diagnosesMargin-negative resectionSingle-institution analysisJohns Hopkins HospitalBeam radiation therapyAbdominopelvic malignanciesRadiotherapy variablesLocoregional controlPerioperative complicationsPerioperative deathsPerioperative morbidityPostoperative complicationsWound complicationsSurgical complicationsCombination 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 activity
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 specialistsTumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients
Fu T, Liu Y, Li K, Wan W, Pappou EP, Iacobuzio-Donahue CA, Kerner Z, Baylin SB, Wolfgang CL, Ahuja N. Tumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients. Oncotarget 2016, 5: 86480-86489. PMID: 27880934, PMCID: PMC5349928, DOI: 10.18632/oncotarget.13441.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedColorectal NeoplasmsCpG IslandsDNA MethylationFemaleHumansMaleMiddle AgedMutL Protein Homolog 1Neoplasm StagingPhenotypePrognosisConceptsDisease-free survivalStage II colorectal cancer patientsStage II CRC patientsCpG island methylator phenotypeMLH1 methylation statusColorectal cancer patientsOverall survivalLymphovascular invasionCRC patientsCancer patientsMucin productionMethylator phenotypeKaplan-Meier analysisPoor clinical outcomeMethylation statusDuodenal adenocarcinomaClinical outcomesAggressive featuresPoor prognosisPrognostic valuePatient subgroupsTumor locationMultivariate analysisPatientsM groupIGFBP-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
Spectrin Repeat Containing Nuclear Envelope 1 and Forkhead Box Protein E1 Are Promising Markers for the Detection of Colorectal Cancer in Blood
Melotte V, Yi JM, Lentjes MH, Smits KM, Van Neste L, Niessen HE, Wouters KA, Louwagie J, Schuebel KE, Herman JG, Baylin SB, van Criekinge W, Meijer GA, Ahuja N, van Engeland M. Spectrin Repeat Containing Nuclear Envelope 1 and Forkhead Box Protein E1 Are Promising Markers for the Detection of Colorectal Cancer in Blood. Cancer Prevention Research 2015, 8: 157-164. PMID: 25538088, PMCID: PMC4316751, DOI: 10.1158/1940-6207.capr-14-0198.Peer-Reviewed Original ResearchAgedArea Under CurveBiomarkers, TumorCell Line, TumorColorectal NeoplasmsCytoskeletal ProteinsDNA MethylationFemaleForkhead Transcription FactorsHumansMaleMiddle AgedNerve Tissue ProteinsNuclear ProteinsPromoter Regions, GeneticReal-Time Polymerase Chain ReactionROC CurveSensitivity and SpecificityTransfection
2014
The promise of methylation on beads for cancer detection and treatment
Guzzetta AA, Pisanic T, Sharma P, Yi JM, Stark A, Wang TH, Ahuja N. The promise of methylation on beads for cancer detection and treatment. Expert Review Of Molecular Diagnostics 2014, 14: 845-852. PMID: 25136840, PMCID: PMC4427839, DOI: 10.1586/14737159.2014.943665.Peer-Reviewed Original ResearchConceptsChoice of treatmentPrognostic value of CpG island methylator phenotype among colorectal cancer patients: a systematic review and meta-analysis
Juo YY, Johnston FM, Zhang DY, Juo HH, Wang H, Pappou EP, Yu T, Easwaran H, Baylin S, van Engeland M, Ahuja N. Prognostic value of CpG island methylator phenotype among colorectal cancer patients: a systematic review and meta-analysis. Annals Of Oncology 2014, 25: 2314-2327. PMID: 24718889, PMCID: PMC4239805, DOI: 10.1093/annonc/mdu149.Peer-Reviewed Original ResearchConceptsDisease-free survivalCpG island methylator phenotypeColorectal cancer patientsCRC patientsOverall survivalHazard ratioPredictive factorsPrognostic valueCancer patientsPredictive valuePatient disease-free survivalShorter disease-free survivalCancer-specific mortalityAdditional survival benefitMethylator phenotypeShorter overall survivalMicrosatellite instability statusAdjuvant chemotherapyDFS benefitSurvival benefitWorse prognosisCRC prognosisPooled analysisSubgroup analysisNineteen studiesCpG 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 sensitivityGemcitabineIncidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases
Karagkounis G, Torbenson MS, Daniel HD, Azad NS, Diaz LA, Donehower RC, Hirose K, Ahuja N, Pawlik TM, Choti MA. Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases. Cancer 2013, 119: 4137-4144. PMID: 24104864, PMCID: PMC3967132, DOI: 10.1002/cncr.28347.Peer-Reviewed Original ResearchConceptsColorectal liver metastasesSurgical therapyBRAF mutationsLiver metastasesKRAS statusPrognostic impactKRAS mutationsMolecular biomarkersThird of patientsRecurrence-free survivalKRAS gene mutationsPrognostic determinantsColorectal metastasesSurgical cohortWorse survivalClinicopathologic factorsIndependent predictorsCancer surgeryClinicopathologic featuresTumor numberPrognostic significanceBRAF analysisColorectal cancerLiver surgeryLower incidence
2012
Colorectal Cancer Stem Cells—Hype or Real?: Comment on “Combined CD133+/CD44+ Expression as a Prognostic Indicator of Disease-Free Survival in Patients With Colorectal Cancer”
Ahuja N. Colorectal Cancer Stem Cells—Hype or Real?: Comment on “Combined CD133+/CD44+ Expression as a Prognostic Indicator of Disease-Free Survival in Patients With Colorectal Cancer”. JAMA Surgery 2012, 147: 24-25. PMID: 22250107, DOI: 10.1001/archsurg.2011.1218.Peer-Reviewed Original ResearchMeSH KeywordsAC133 AntigenAntigens, CDColorectal NeoplasmsFemaleGlycoproteinsHumansHyaluronan ReceptorsMalePeptides
2011
The CpG island methylator phenotype in colorectal cancer: Progress and problems
Hughes LA, Bakker C, Smits KM, van den Brandt PA, Jonkers D, Ahuja N, Herman JG, Weijenberg MP, van Engeland M. The CpG island methylator phenotype in colorectal cancer: Progress and problems. Biochimica Et Biophysica Acta 2011, 1825: 77-85. PMID: 22056543, DOI: 10.1016/j.bbcan.2011.10.005.Peer-Reviewed Original ResearchConceptsCpG island methylator phenotypeColorectal cancerMethylator phenotypeMolecular pathological epidemiologySporadic colorectal cancerEnvironmental risk factorsPotential clinical importanceMultiple gene panelsOnly original research articlesRisk factorsUnselected seriesInclusion criteriaUnselected casesTrue prevalenceClinical importanceSystematic reviewDisease trendsOriginal research articlesGene panelPrevalenceDistinct subgroupsCancerPrimary causePhenotypeUniversal definition
2009
Methylation of TFPI2 in Stool DNA: A Potential Novel Biomarker for the Detection of Colorectal Cancer
Glöckner S, Dhir M, Yi JM, McGarvey KE, Van Neste L, Louwagie J, Chan TA, Kleeberger W, de Bruïne A, Smits KM, Bakker C, Jonkers DM, Stockbrügger R, Meijer GA, Oort FA, Iacobuzio-Donahue C, Bierau K, Herman JG, Baylin SB, Van Engeland M, Schuebel KE, Ahuja N. Methylation of TFPI2 in Stool DNA: A Potential Novel Biomarker for the Detection of Colorectal Cancer. Cancer Research 2009, 69: 4691-4699. PMID: 19435926, PMCID: PMC3062162, DOI: 10.1158/0008-5472.can-08-0142.Peer-Reviewed Original ResearchConceptsTissue factor pathway inhibitor-2Colorectal cancerStool DNATFPI2 methylationStage INonmetastatic colorectal cancerHuman colorectal cancerPotential novel biomarkersCRC patientsNoncancer controlsColorectal carcinogenesisNovel biomarkersUseful adjunctPotential tumor suppressor geneNoninvasive strategyTumor suppressor geneEarly detectionAberrant DNA methylationPatientsFrequent eventCancerAberrant methylationSuppressor geneBiomarkers