2017
Fluorouracil Enhances Photodynamic Therapy of Squamous Cell Carcinoma via a p53-Independent Mechanism that Increases Protoporphyrin IX levels and Tumor Cell Death
Anand S, Rollakanti KR, Brankov N, Brash DE, Hasan T, Maytin EV. Fluorouracil Enhances Photodynamic Therapy of Squamous Cell Carcinoma via a p53-Independent Mechanism that Increases Protoporphyrin IX levels and Tumor Cell Death. Molecular Cancer Therapeutics 2017, 16: 1092-1101. PMID: 28336806, PMCID: PMC5497500, DOI: 10.1158/1535-7163.mct-16-0608.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiosynthetic PathwaysCarcinoma, Squamous CellCell DeathCell Line, TumorCell ProliferationCombined Modality TherapyDisease Models, AnimalFluorouracilGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHemeHumansMicePhotochemotherapyProtoporphyrinsTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsSquamous cell carcinomaActinic keratosesPhotodynamic therapyP53-null tumorsNew therapeutic approachesMol Cancer TherCell deathCell carcinomaTherapeutic responsePpIX levelsTherapeutic approachesMouse modelSkin cancerSCC precursorsHeme synthesis pathwayTumorsKeratosesDeathP53PDT efficacyInductionPretreatmentNeoadjuvantCombination approachSurgery
2009
Stochastic fate of p53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia
Klein AM, Brash DE, Jones PH, Simons BD. Stochastic fate of p53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 107: 270-275. PMID: 20018764, PMCID: PMC2806764, DOI: 10.1073/pnas.0909738107.Peer-Reviewed Original ResearchConceptsP53 mutationsNonmelanoma skin cancer incidenceSame cumulative doseSkin cancer incidenceUVB radiationUV-irradiated epidermisP53 tumor suppressor geneP53-mutant clonesCumulative doseCancer incidenceP53 mutant cellsHigh-intensity exposureMurine epidermisPreneoplastic clonesTumor suppressor geneProgenitor cellsExposure resultsPrecancerous cellsPreneoplastic cellsHuman epidermisB radiationClones of cells
2008
Preneoplastic lesion growth driven by the death of adjacent normal stem cells
Chao DL, Eck JT, Brash DE, Maley CC, Luebeck EG. Preneoplastic lesion growth driven by the death of adjacent normal stem cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 15034-15039. PMID: 18815380, PMCID: PMC2567488, DOI: 10.1073/pnas.0802211105.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisClone CellsComputer SimulationEpidermisMiceModels, BiologicalPrecancerous ConditionsSkin NeoplasmsStem CellsTumor Suppressor Protein p53Ultraviolet RaysConceptsNormal stem cellsStem cellsClonal expansionCell replicationMutant cellsNormal cell replicationMutant clonesProliferative advantageDorsal epidermisCell mutationTissue architectureClonesClone growthBiological observationsCell killingApoptosis rateReplicationMutationsGrowth rateCellsGrowthNormal territoriesApoptosisExponential growth modelImportant stepProgressive apoptosis resistance prior to senescence and control by the anti-apoptotic protein BCL-xL
Rochette PJ, Brash DE. Progressive apoptosis resistance prior to senescence and control by the anti-apoptotic protein BCL-xL. Mechanisms Of Ageing And Development 2008, 129: 207-214. PMID: 18262222, PMCID: PMC2652169, DOI: 10.1016/j.mad.2007.12.007.Peer-Reviewed Original ResearchMeSH KeywordsAdultApoptosisBcl-X ProteinCells, CulturedCellular SenescenceDiploidyFemaleFibroblastsHumansRNA, Small InterferingTelomereTumor Suppressor Protein p53ConceptsAnti-apoptotic protein Bcl-xLBcl-xLProtein Bcl-xLLevels of p53Pro-apoptotic protein BaxApoptosis reductionAnti-apoptotic proteinsPro-apoptotic BaxNormal balanceAnti-apoptotic Bcl-xLUV-induced apoptosisOld cellsApoptosis resistanceProgressive disruptionSenescent cellsApoptosisBaxProtein BaxHuman diploid fibroblastsCellsYoung cellsDiploid fibroblastsGenotoxic stressLevels
2007
Bcl-2 is the target of a UV-inducible apoptosis switch and a node for UV signaling
Knezevic D, Zhang W, Rochette PJ, Brash DE. Bcl-2 is the target of a UV-inducible apoptosis switch and a node for UV signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 11286-11291. PMID: 17586682, PMCID: PMC2040891, DOI: 10.1073/pnas.0701318104.Peer-Reviewed Original Research
2005
Knockdown of p53 levels in human keratinocytes accelerates Mcl-1 and Bcl-xL reduction thereby enhancing UV-light induced apoptosis
Chaturvedi V, Sitailo LA, Qin JZ, Bodner B, Denning MF, Curry J, Zhang W, Brash D, Nickoloff BJ. Knockdown of p53 levels in human keratinocytes accelerates Mcl-1 and Bcl-xL reduction thereby enhancing UV-light induced apoptosis. Oncogene 2005, 24: 5299-5312. PMID: 15940268, DOI: 10.1038/sj.onc.1208650.Peer-Reviewed Original ResearchConceptsMouse modelP53 levelsP53 siRNAHuman keratinocytesMcl-1Skin cancer developmentKnockout mouse modelP53 tumor suppressor geneCultured human keratinocytesBcl-xL antiapoptotic proteinBcl-xL levelsCommon causeParadoxical responseSkin cancerAccelerated eliminationUltraviolet light exposureWild-type p53Cancer developmentTumor suppressor geneUV-induced DNA damageEpidermal responseE2F-1 levelsPrimary culturesSiRNA-based approachAbnormal cellsColonization of adjacent stem cell compartments by mutant keratinocytes
Brash DE, Zhang W, Grossman D, Takeuchi S. Colonization of adjacent stem cell compartments by mutant keratinocytes. Seminars In Cancer Biology 2005, 15: 97-102. PMID: 15652454, DOI: 10.1016/j.semcancer.2004.08.006.ChaptersMeSH KeywordsAnimalsApoptosisKeratinocytesMutagenesisSkin NeoplasmsStem CellsTumor Suppressor Protein p53Ultraviolet RaysConceptsStem cell compartmentMutant stem cellsCell compartmentStem cellsDNA-damaged cellsNon-mutational mechanismsMutant cellsAdditional genesClonal expansionSelection pressureP53 mutant cellsUVB-induced apoptosisMutant keratinocytesCancer developmentCompartmentsCellsAbsence of escapeKeratinocyte clonesAdditional territoryClinical phenotypeAdjacent compartmentsGenesMechanismClonesPhenotype
2004
UVB-induced apoptosis drives clonal expansion during skin tumor development
Zhang W, Hanks AN, Boucher K, Florell SR, Allen SM, Alexander A, Brash DE, Grossman D. UVB-induced apoptosis drives clonal expansion during skin tumor development. Carcinogenesis 2004, 26: 249-257. PMID: 15498793, PMCID: PMC2292404, DOI: 10.1093/carcin/bgh300.Peer-Reviewed Original Research
2003
Antigen-specific immunity does not mediate acute regression of UVB-induced p53-mutant clones
Remenyik É, Wikonkál NM, Zhang W, Paliwal V, Brash DE. Antigen-specific immunity does not mediate acute regression of UVB-induced p53-mutant clones. Oncogene 2003, 22: 6369-6376. PMID: 14508517, DOI: 10.1038/sj.onc.1206657.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHomeodomain ProteinsHumansImmune SystemMiceMice, KnockoutMutationTumor Suppressor Protein p53Ultraviolet RaysConceptsAntigen-specific immunityP53-mutant clonesUltraviolet BAcute regressionNatural killer T cellsKiller T cellsRag1 knockout miceChronic UVB irradiationMurine skin tumorsInduction of carcinomasSignificant differencesUVB carcinogenesisT cellsSkin tumorsKnockout micePersistence of clonesEpidermal thicknessMurine epidermisUVB irradiationEpidermal sheetsImmunityChronic irradiationGene 1MiceRegressionInactivating E2f1 reverts apoptosis resistance and cancer sensitivity in Trp53-deficient mice
Wikonkal NM, Remenyik E, Knezevic D, Zhang W, Liu M, Zhao H, Berton TR, Johnson DG, Brash DE. Inactivating E2f1 reverts apoptosis resistance and cancer sensitivity in Trp53-deficient mice. Nature Cell Biology 2003, 5: 655-660. PMID: 12833065, DOI: 10.1038/ncb1001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Cycle ProteinsCell SurvivalCell Transformation, NeoplasticCells, CulturedDNA DamageDNA-Binding ProteinsE2F Transcription FactorsE2F1 Transcription FactorFemaleFibroblastsGene Expression Regulation, NeoplasticGenes, SuppressorKeratinocytesMaleMiceMice, KnockoutMutationSex RatioSkin NeoplasmsTranscription FactorsTumor Suppressor Protein p53Ultraviolet RaysConceptsUVB-induced apoptosisEarly-onset tumorsDouble knockout miceTrp53-deficient miceKnockout miceCancer sensitivityUVB exposureGenetic abnormalitiesMiceKeratinocyte apoptosisProtective mechanismApoptosis defectsApoptosis resistanceApoptosisDouble knockoutApoptosis pathwayE2F1 transcription factorE2F1 functionsPrimary fibroblastsE2F1Trp53S phase
2002
New careers for antioxidants
Brash DE, Havre PA. New careers for antioxidants. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 13969-13971. PMID: 12391310, PMCID: PMC137820, DOI: 10.1073/pnas.232574399.Commentaries, Editorials and LettersTransformed and tumor-derived human cells exhibit preferential sensitivity to the thiol antioxidants, N-acetyl cysteine and penicillamine.
Havre PA, O'Reilly S, McCormick JJ, Brash DE. Transformed and tumor-derived human cells exhibit preferential sensitivity to the thiol antioxidants, N-acetyl cysteine and penicillamine. Cancer Research 2002, 62: 1443-9. PMID: 11888918.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAntioxidantsApoptosisCell LineCell Transformation, NeoplasticFibroblastsGenes, mycHumansNeoplasmsPenicillamineTumor Suppressor Protein p53ConceptsMouse embryo fibroblasts
2001
Escaping the stem cell compartment: Sustained UVB exposure allows p53-mutant keratinocytes to colonize adjacent epidermal proliferating units without incurring additional mutations
Zhang W, Remenyik E, Zelterman D, Brash D, Wikonkal N. Escaping the stem cell compartment: Sustained UVB exposure allows p53-mutant keratinocytes to colonize adjacent epidermal proliferating units without incurring additional mutations. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 13948-13953. PMID: 11707578, PMCID: PMC61147, DOI: 10.1073/pnas.241353198.Peer-Reviewed Original ResearchThe DNA Damage Signal for Mdm2 Regulation, Trp53 Induction, and Sunburn Cell Formation In Vivo Originates from Actively Transcribed Genes
Brash D, Wikonkal N, Remenyik E, van der Horst G, Friedberg E, Cheo D, van Steeg H, Westerman A, van Kranen H. The DNA Damage Signal for Mdm2 Regulation, Trp53 Induction, and Sunburn Cell Formation In Vivo Originates from Actively Transcribed Genes. Journal Of Investigative Dermatology 2001, 117: 1234-1240. PMID: 11710938, DOI: 10.1046/j.0022-202x.2001.01554.x.Peer-Reviewed Original ResearchConceptsDNA photoproductsDNA damage signalsUnrepaired DNA lesionsCell formationSpecific genome regionsTumor suppressor proteinCsb-/- miceUltraviolet-induced apoptosisNucleotide excision repair genesApoptosis signal pathwayExcision repair genesActive genesMutant cellsGenome regionsDNA repairSuppressor proteinDamage signalsMDM2 regulationWild typeDNA lesionsPrevents cellsHomozygous inactivationGenesRepair genesDNA signalsTransgenic expression of survivin in keratinocytes counteracts UVB-induced apoptosis and cooperates with loss of p53
Grossman D, Kim P, Blanc-Brude O, Brash D, Tognin S, Marchisio P, Altieri D. Transgenic expression of survivin in keratinocytes counteracts UVB-induced apoptosis and cooperates with loss of p53. Journal Of Clinical Investigation 2001, 108: 991-999. PMID: 11581300, PMCID: PMC200956, DOI: 10.1172/jci13345.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisChromosomal Proteins, Non-HistoneGene ExpressionHumansInhibitor of Apoptosis ProteinsKeratin-14KeratinocytesKeratinsMiceMice, KnockoutMice, TransgenicMicrotubule-Associated ProteinsNeoplasm ProteinsPhenotypePromoter Regions, GeneticSkinSurvivinTumor Suppressor Protein p53Ultraviolet Rays
1999
Induction of cyclin-dependent kinase inhibitors and G1 prolongation by the chemopreventive agent N-acetylcysteine
Liu M, Wikonkal N, Brash D. Induction of cyclin-dependent kinase inhibitors and G1 prolongation by the chemopreventive agent N-acetylcysteine. Carcinogenesis 1999, 20: 1869-1872. PMID: 10469636, DOI: 10.1093/carcin/20.9.1869.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsAnticarcinogenic AgentsAntioxidantsCell CycleCell LineChromansCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p21CyclinsFibroblastsFree Radical ScavengersG1 PhaseGene Expression RegulationGene Expression Regulation, NeoplasticGenes, p16GlutathioneHumansKeratinocytesMiceModels, BiologicalNeoplasm ProteinsPapillomaSkin NeoplasmsTumor Cells, CulturedTumor Suppressor Protein p53ConceptsCyclin-dependent kinase inhibitorNovel molecular basisCell cycle transitionKinase inhibitorsDNA replicationDNA repairCellular differentiationMolecular basisG1 prolongationGene expressionAntioxidant N-acetylcysteineN-acetylcysteineIntracellular glutathione levelsArrestAgent N-acetylcysteineInductionInhibitorsGlutathione levelsCyclinChemopreventive agentsChemopreventive activityDifferentiationUsual mechanismP53ReplicationUV Induces p21WAF1/CIP1 Protein in Keratinocytes Without p53
Liu M, Wikonkal N, Brash D. UV Induces p21WAF1/CIP1 Protein in Keratinocytes Without p53. Journal Of Investigative Dermatology 1999, 113: 283-284. PMID: 10469320, DOI: 10.1046/j.1523-1747.1999.00657.x.Peer-Reviewed Original ResearchCyclin-Dependent Kinase Inhibitor p21CyclinsDNA ReplicationHumansKeratinocytesTumor Suppressor Protein p53Ultraviolet Rays
1998
Antioxidant action via p53-mediated apoptosis.
Liu M, Pelling JC, Ju J, Chu E, Brash DE. Antioxidant action via p53-mediated apoptosis. Cancer Research 1998, 58: 1723-9. PMID: 9563490.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsAntioxidantsApoptosisBlotting, NorthernBlotting, WesternButhionine SulfoximineCells, CulturedDimercaprolDose-Response Relationship, DrugGene Expression Regulation, NeoplasticGlutathioneMiceOxidation-ReductionPyrrolidonecarboxylic AcidSulfhydryl CompoundsThiazolesThiazolidinesTumor Cells, CulturedTumor Suppressor Protein p53Vitamin EConceptsP53 inductionCellular redox potentialP53-dependent apoptosisNormal cellsP53-mediated apoptosisTumor suppressor geneP53 mRNA translationCellular thiol levelsMRNA translationRedox sensorProtein stabilitySuppressor geneP53 tumor suppressor geneNontoxic antioxidantsApoptosisCell linesSulfur-containing antioxidantsBiological effectsPrimary culturesElevated p53 expressionCellsInductionN-acetylcysteineGlutathione levelsRedox potential
1996
Cellular proofreading
Brash D. Cellular proofreading. Nature Medicine 1996, 2: 525-526. PMID: 8616708, DOI: 10.1038/nm0596-525.Commentaries, Editorials and Letters
1992
Status of the p53 tumor suppressor gene in human squamous carcinoma cell lines.
Reiss M, Brash DE, Muñoz-Antonia T, Simon JA, Ziegler A, Vellucci VF, Zhou ZL. Status of the p53 tumor suppressor gene in human squamous carcinoma cell lines. Oncology Research Featuring Preclinical And Clinical Cancer Therapeutics 1992, 4: 349-57. PMID: 1486218.Peer-Reviewed Original Research