2020
Pandemic Recovery Using a COVID-Minimal Cancer Surgery Pathway
Boffa DJ, Judson BL, Billingsley KG, Galetta D, Fontanez P, Odermatt C, Lindner K, Mitchell MR, Henderson CM, Carafeno T, Pinto J, Wagner J, Ancuta M, Beley P, Turner AL, Banack T, Laurans MS, Johnson DC, Yoo P, Morton JM, Zurich H, Davis K, Ahuja N. Pandemic Recovery Using a COVID-Minimal Cancer Surgery Pathway. The Annals Of Thoracic Surgery 2020, 110: 718-724. PMID: 32417195, PMCID: PMC7227551, DOI: 10.1016/j.athoracsur.2020.05.003.Peer-Reviewed Original ResearchConceptsSurgery pathwayHospital-acquired COVID-19 infectionLarge academic medical centerCOVID-19 patientsCoronavirus disease 2019 (COVID-19) pandemicCOVID-19 infectionPatient care pathwayAcademic medical centerDisease 2019 pandemicHealth care deliveryOnly surgerySurgery populationElective surgeryPatient survivalRisk of exposureProtection of patientsCare pathwayNosocomial infectionsMedical CenterCare deliverySurgical activityHospitalPatientsSurgeryMost hospitalsExposing 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
2019
A phase 1 trial of the oral DNA methyltransferase inhibitor CC‐486 and the histone deacetylase inhibitor romidepsin in advanced solid tumors
Gaillard SL, Zahurak M, Sharma A, Durham J, Reiss K, Sartorius‐Mergenthaler S, Downs M, Anders N, Ahuja N, Rudek M, Azad N. A phase 1 trial of the oral DNA methyltransferase inhibitor CC‐486 and the histone deacetylase inhibitor romidepsin in advanced solid tumors. Cancer 2019, 125: 2837-2845. PMID: 31012962, PMCID: PMC6663621, DOI: 10.1002/cncr.32138.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAged, 80 and overAnorexiaAntineoplastic Combined Chemotherapy ProtocolsAzacitidineDepsipeptidesDNA Modification MethylasesDrug Administration ScheduleFemaleHistone Deacetylase InhibitorsHumansLong Interspersed Nucleotide ElementsMaleMaximum Tolerated DoseMethyltransferasesMiddle AgedNauseaNeoplasmsConceptsHistone deacetylase inhibitor romidepsinDisease control rateAdvanced solid tumorsPhase 1 studyCC-486Solid tumorsDose-escalation portionPhase 2 doseDose-limiting toxicityPossible clinical benefitPhase 1 trialDose-escalation designElement-1 methylationLINE-1 methylationStable diseaseCommon toxicitiesDose expansionExpansion cohortPrimary outcomeClinical benefitControl rateDrug exposureBlood samplesDay 1Dose levels
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
The Roles of DNA Methylation in the Stages of Cancer
McMahon KW, Karunasena E, Ahuja N. The Roles of DNA Methylation in the Stages of Cancer. The Cancer Journal 2017, 23: 257-261. PMID: 28926425, PMCID: PMC5657558, DOI: 10.1097/ppo.0000000000000279.Peer-Reviewed Original ResearchEpigenetic therapy and chemosensitization in solid malignancy
Ronnekleiv-Kelly SM, Sharma A, Ahuja N. Epigenetic therapy and chemosensitization in solid malignancy. Cancer Treatment Reviews 2017, 55: 200-208. PMID: 28431263, DOI: 10.1016/j.ctrv.2017.03.008.Peer-Reviewed Original ResearchConceptsCombination therapyEpigenetic therapySpecific hematologic malignanciesCertain solid tumorsHistone deacetylase inhibitorsDurable responsesSystemic therapyPatient subsetsSolid malignanciesHematologic malignanciesOvarian cancerBreast cancerDNA methyltransferase inhibitorEpigenetic changesSolid tumorsDeacetylase inhibitorsStandard chemotherapeuticsTherapyClinical potentialCancer cellsTrialsNSCLCMalignancyMethyltransferase inhibitorHypermethylation patterns
2016
Combining Epigenetic and Immunotherapy to Combat Cancer
Chiappinelli KB, Zahnow CA, Ahuja N, Baylin SB. Combining Epigenetic and Immunotherapy to Combat Cancer. Cancer Research 2016, 76: 1683-1689. PMID: 26988985, PMCID: PMC4873370, DOI: 10.1158/0008-5472.can-15-2125.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitor efficacyCheckpoint inhibitor efficacyImmune checkpoint blockadeCurrent clinical trialsT-cell attractionException of melanomaAdvanced human cancersCancer management strategiesEpithelial cancer cellsCheckpoint blockadeMost patientsCombination therapyCancer testisClinical trialsDNA methyltransferase inhibitorMouse modelInhibitor efficacyImmune signalingCancer cellsHuman cancersMethyltransferase inhibitorEpigenetic drugsDemethylating agentExciting recent advancesEndogenous retrovirusesEpigenetic Therapeutics: A New Weapon in the War Against Cancer
Ahuja N, Sharma AR, Baylin SB. Epigenetic Therapeutics: A New Weapon in the War Against Cancer. Annual Review Of Medicine 2016, 67: 73-89. PMID: 26768237, PMCID: PMC4937439, DOI: 10.1146/annurev-med-111314-035900.Peer-Reviewed Original ResearchConceptsEpigenetic therapyPrimary base sequenceNucleosome positioningEpigenetic regulationCellular regulationHeritable patternsEpigenetic mechanismsDNA methylationExplosion of discoveriesGene expressionCancer initiationBase sequenceEpigenomeRegulationFrequent mutationsGenetic abnormalitiesNormal maturationTumor cellsPotent toolChromatinCellsNeoplastic cellsGenesMethylationProtein
2015
Epigenetic 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
Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers
Li H, Chiappinelli KB, Guzzetta AA, Easwaran H, Yen RW, Vatapalli R, Topper MJ, Luo J, Connolly RM, Azad NS, Stearns V, Pardoll DM, Davidson N, Jones PA, Slamon DJ, Baylin SB, Zahnow CA, Ahuja N. Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers. Oncotarget 2014, 5: 587-598. PMID: 24583822, PMCID: PMC3996658, DOI: 10.18632/oncotarget.1782.Peer-Reviewed Original ResearchConceptsDNA methyltransferase inhibitorImmune gene setsImmune-stimulatory roleCytokines/chemokinesCancer-testis antigensGene expression subsetsMethyltransferase inhibitorEpigenetic therapyHuman epithelial cancersMechanism of actionCancer cell linesPrimary tumorGene Set Enrichment AnalysisImmunomodulatory pathwaysImmune regulationPotential therapyTestis antigensPatient biopsiesSolid tumorsEpithelial cancersMultiple cancersLow dosesTumor expression dataAntigen processingTherapyHarnessing 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
The 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
2012
A DNA hypermethylation module for the stem/progenitor cell signature of cancer
Easwaran H, Johnstone SE, Van Neste L, Ohm J, Mosbruger T, Wang Q, Aryee MJ, Joyce P, Ahuja N, Weisenberger D, Collisson E, Zhu J, Yegnasubramanian S, Matsui W, Baylin SB. A DNA hypermethylation module for the stem/progenitor cell signature of cancer. Genome Research 2012, 22: 837-849. PMID: 22391556, PMCID: PMC3337430, DOI: 10.1101/gr.131169.111.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorChromatinCluster AnalysisCpG IslandsDNA MethylationEmbryonic Stem CellsEpigenesis, GeneticGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, NeoplasmGenes, RegulatorHistonesHumansMesenchymal Stem CellsNeoplasmsOligonucleotide Array Sequence AnalysisOsteoblastsPolycomb-Group ProteinsPromoter Regions, GeneticRepressor ProteinsSequence Analysis, DNAConceptsEmbryonic stem cellsBivalent chromatinDevelopmental regulatorsPcG target genesKey developmental regulatorsGenome-wide analysisSubset of genesPolycomb repressor complexesStem cellsAdult stem/progenitor cellsStem-like stateStem/progenitor cellsTranscription statePcG genesRepressor complexNormal stem cellsChromatin statusHypermethylated genesTarget genesDNA hypermethylationCancer genesGlobal methylationChromatinGenesMethylation status
2010
Translational Research in Surgical Disease
Stojadinovic A, Ahuja N, Nazarian SM, Segev DL, Jacobs L, Wang Y, Eberhardt J, Zeiger MA. Translational Research in Surgical Disease. JAMA Surgery 2010, 145: 187-196. PMID: 20157088, DOI: 10.1001/archsurg.2009.280.Peer-Reviewed Original Research
2008
Pancreatic Resection of Isolated Metastases from Nonpancreatic Primary Cancers
Reddy S, Edil BH, Cameron JL, Pawlik TM, Herman JM, Gilson MM, Campbell KA, Schulick RD, Ahuja N, Wolfgang CL. Pancreatic Resection of Isolated Metastases from Nonpancreatic Primary Cancers. Annals Of Surgical Oncology 2008, 15: 3199-3206. PMID: 18784960, DOI: 10.1245/s10434-008-0140-7.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaPancreatic resectionMetachronous lesionsMetastatic lesionsVascular invasionConclusionLong-term survivalResultsForty-nine patientsLymph node metastasisLangerhans cell histiocytosisDistal pancreatectomyPerioperative deathsPostoperative morbidityTotal pancreatectomyIsolated metastasisMedian survivalMetastatic diseaseSynchronous lesionsNode metastasisPrimary diseasePrimary cancerMedian lengthCell carcinomaGallbladder cancerSingle institutionCell histiocytosis
2000
Aging, methylation and cancer.
Ahuja N, Issa JP. Aging, methylation and cancer. Histology And Histopathology 2000, 15: 835-42. PMID: 10963127, DOI: 10.14670/hh-15.835.Peer-Reviewed Original ResearchConceptsAge-related methylationSuch age-related methylationPromoter-associated CpG islandsTumor suppressor geneGene functionDNA methylationCpG islandsMethylation changesFull methylationGene expressionMethylationGenesNovel targetNormal cellsColon cancerAlternate mechanismMost cancersEvidence pointsFundamental markMyoDIGF2HypermethylationDNAERMutations