2023
Harnessing small extracellular vesicles for pro-oxidant delivery: novel approach for drug-sensitive and resistant cancer therapy
Kang C, Ren X, Lee D, Ramesh R, Nimmo S, Yang-Hartwich Y, Kim D. Harnessing small extracellular vesicles for pro-oxidant delivery: novel approach for drug-sensitive and resistant cancer therapy. Journal Of Controlled Release 2023, 365: 286-300. PMID: 37992875, PMCID: PMC10872719, DOI: 10.1016/j.jconrel.2023.11.031.Peer-Reviewed Original ResearchSmall extracellular vesiclesMDR cancer cellsMultidrug resistanceCancer cellsDrug resistanceReactive oxygen speciesExtracellular vesiclesOvarian cancer cellsDrug-resistant cancersApoptotic cell deathCancer treatment strategiesTreatment strategiesTherapy highlightClinical problemMDR tumorsDrug responsivenessP-glycoproteinPotent anticancer activityCancer treatmentRedox balanceATP productionOxidative stressTumorsVivo studiesMitochondrial dysfunctionNRF2 controls iron homeostasis and ferroptosis through HERC2 and VAMP8
Anandhan A, Dodson M, Shakya A, Chen J, Liu P, Wei Y, Tan H, Wang Q, Jiang Z, Yang K, Garcia J, Chambers S, Chapman E, Ooi A, Yang-Hartwich Y, Stockwell B, Zhang D. NRF2 controls iron homeostasis and ferroptosis through HERC2 and VAMP8. Science Advances 2023, 9: eade9585. PMID: 36724221, PMCID: PMC9891695, DOI: 10.1126/sciadv.ade9585.Peer-Reviewed Original ResearchConceptsLabile iron poolNFE2L2/Human ovarian cancer tissuesCancer cellsOvarian cancer cell linesOvarian cancer tissuesIntracellular labile iron poolIron homeostasisCancer cell linesPreclinical modelsNrf2 inhibitionCancer tissuesNrf2 levelsCancer treatmentFerroptotic deathNrf2Ferroptosis resistanceKnockout cellsCell linesUntapped strategyFerroptosisIron poolCellsHomeostasisExpression
2021
A Benzenesulfonamide-based Mitochondrial Uncoupler Induces Endoplasmic Reticulum Stress and Immunogenic Cell Death in Epithelial Ovarian Cancer
Bi F, Jiang Z, Park W, Hartwich TMP, Ge Z, Chong KY, Yang K, Morrison MJ, Kim D, Kim J, Zhang W, Kril LM, Watt DS, Liu C, Yang-Hartwich Y. A Benzenesulfonamide-based Mitochondrial Uncoupler Induces Endoplasmic Reticulum Stress and Immunogenic Cell Death in Epithelial Ovarian Cancer. Molecular Cancer Therapeutics 2021, 20: molcanther.mct-21-0396-a.2021. PMID: 34625503, PMCID: PMC8643344, DOI: 10.1158/1535-7163.mct-21-0396.Peer-Reviewed Original ResearchConceptsEpithelial ovarian cancerImmunogenic cell deathOvarian cancerTumor progressionAntitumor adaptive immune responsesDamage-associated molecular patternsCancer cellsMitochondrial uncouplerAdaptive immune responsesOvarian cancer modelCause of deathCurrent chemotherapeutic agentsNew therapeutic strategiesOvarian cancer cellsCancer cell proliferationCell deathEndoplasmic reticulum stressGynecologic malignanciesClinical outcomesEndoplasmic reticulum stress sensorNew anticancer therapiesPeritoneal fluidInduces Endoplasmic Reticulum StressImmune responseAbdominal cavity
2016
TRX-E-002-1 Induces c-Jun–Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo
Alvero AB, Heaton A, Lima E, Pitruzzello M, Sumi N, Yang-Hartwich Y, Cardenas C, Steinmacher S, Silasi DA, Brown D, Mor G. TRX-E-002-1 Induces c-Jun–Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo. Molecular Cancer Therapeutics 2016, 15: 1279-1290. PMID: 27196760, DOI: 10.1158/1535-7163.mct-16-0005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Line, TumorCell ProliferationCell SurvivalCisplatinDrug Resistance, NeoplasmDrug SynergismFemaleFlavonoidsGene Expression Regulation, NeoplasticHumansMiceNeoplasm Recurrence, LocalNeoplasm TransplantationNeoplastic Stem CellsOvarian NeoplasmsPhosphorylationProto-Oncogene Proteins c-junSignal TransductionXenograft Model Antitumor AssaysConceptsCancer stem cellsOvarian cancer cellsTumor burdenOvarian cancerCancer cellsChemoresistant cancer stem cellsOvarian cancer stem cellsIntraperitoneal tumor burdenRecurrent ovarian cancerBest therapeutic optionManagement of patientsCombination of cisplatinEpithelial ovarian cancerCell deathStem cellsTumor repairDisease recurrenceMaintenance treatmentPatient survivalTherapeutic optionsHigh mortalityStemness propertiesMonotherapyDeathVehicle control
2014
p53 protein aggregation promotes platinum resistance in ovarian cancer
Yang-Hartwich Y, Soteras MG, Lin ZP, Holmberg J, Sumi N, Craveiro V, Liang M, Romanoff E, Bingham J, Garofalo F, Alvero A, Mor G. p53 protein aggregation promotes platinum resistance in ovarian cancer. Oncogene 2014, 34: 3605-3616. PMID: 25263447, DOI: 10.1038/onc.2014.296.Peer-Reviewed Original ResearchConceptsPro-apoptotic functionP53 aggregationProtein aggregationP53 aggregatesNormal transcriptional activationTwo-dimensional gel electrophoresisCancer cellsCancer cell survivalKey transcriptional factorGenetic mutationsHigh-grade serous ovarian carcinomaP53 inactivationP53 proteinStem cell propertiesCancer stem cell propertiesCellular homeostasisTranscriptional activationCancer stem cellsTranscriptional factorsTumor-initiating capacityP53 turnoverCell survivalHGSOC cellsStem cellsPotential therapeutic targetDetection of p53 Protein Transcriptional Activity by Chromatin Immunoprecipitation
Yang-Hartwich Y, Romanoff E, Bingham J, Alvero AB, Mor G. Detection of p53 Protein Transcriptional Activity by Chromatin Immunoprecipitation. Methods In Molecular Biology 2014, 1219: 87-93. PMID: 25308264, DOI: 10.1007/978-1-4939-1661-0_8.Peer-Reviewed Original ResearchConceptsTranscriptional activityP53 transcriptional activityChromatin immunoprecipitationTranscription-dependent activityDNA-binding domainExpression of hundredsImportant cellular functionsKey transcriptional mediatorAbility of p53Protein's transcriptional activityP53-induced apoptosisResult of mutationsGenome integrityCellular homeostasisCellular functionsTranscriptional mediatorsTarget genesPromoter regionApoptotic genesCell deathReal-time quantitative polymerase chain reactionCancer cellsQuantitative polymerase chain reactionImmunoprecipitationGenesDetection of p53 Protein Aggregation in Cancer Cell Lines and Tumor Samples
Yang-Hartwich Y, Bingham J, Garofalo F, Alvero AB, Mor G. Detection of p53 Protein Aggregation in Cancer Cell Lines and Tumor Samples. Methods In Molecular Biology 2014, 1219: 75-86. PMID: 25308263, DOI: 10.1007/978-1-4939-1661-0_7.Peer-Reviewed Original ResearchConceptsCancer cell linesPro-apoptotic functionAggregation of p53P53 proteinCancer cellsCell linesP53 aggregationAmyloid-like oligomersProtein aggregationApoptotic signalsInactive conformationTumor samplesFunctional p53ProteinGenetic mutationsTumor progressionCentral roleP53Dysfunctional p53 proteinCellsAggregationMutationsApoptosisDeregulationLines
2013
TLR2 enhances ovarian cancer stem cell self-renewal and promotes tumor repair and recurrence
Chefetz I, Alvero A, Holmberg J, Lebowitz N, Craveiro V, Yang-Hartwich Y, Yin G, Squillace L, Soteras M, Aldo P, Mor G. TLR2 enhances ovarian cancer stem cell self-renewal and promotes tumor repair and recurrence. Cell Cycle 2013, 12: 511-521. PMID: 23324344, PMCID: PMC3587452, DOI: 10.4161/cc.23406.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, Ovarian EpithelialDrug Resistance, NeoplasmFemaleHomeodomain ProteinsHumansHyaluronan ReceptorsInflammationMiceMice, NudeMyeloid Differentiation Factor 88Nanog Homeobox ProteinNeoplasm Recurrence, LocalNeoplasms, Glandular and EpithelialNeoplastic Stem CellsNF-kappa BOctamer Transcription Factor-3Ovarian NeoplasmsSOXB1 Transcription FactorsToll-Like Receptor 2Tumor Cells, CulturedTumor MicroenvironmentConceptsOvarian cancer stem cellsCancer stem cellsTumor repairEOC stem cellsTLR2-MyD88NFκB pathwaySpecific pro-inflammatory pathwaysStem cellsMajority of patientsEpithelial ovarian cancer stem cellsPrimary ovarian cancerPro-inflammatory pathwaysPro-inflammatory microenvironmentCell populationsStemness-associated genesChemoresistant recurrent diseaseRecurrent diseaseEOC patientsRecent compelling evidenceOvarian cancerTumor injuryRecurrenceCancer cell populationsTumor initiationCancer cells
2012
Constitutive proteasomal degradation of TWIST-1 in epithelial–ovarian cancer stem cells impacts differentiation and metastatic potential
Yin G, Alvero AB, Craveiro V, Holmberg JC, Fu HH, Montagna MK, Yang Y, Chefetz-Menaker I, Nuti S, Rossi M, Silasi DA, Rutherford T, Mor G. Constitutive proteasomal degradation of TWIST-1 in epithelial–ovarian cancer stem cells impacts differentiation and metastatic potential. Oncogene 2012, 32: 39-49. PMID: 22349827, PMCID: PMC3703656, DOI: 10.1038/onc.2012.33.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationFemaleHumansHyaluronan ReceptorsMiceMyeloid Differentiation Factor 88Neoplasm MetastasisNeoplasms, Glandular and EpithelialNeoplastic Stem CellsNuclear ProteinsOvarian NeoplasmsProteasome Endopeptidase ComplexProteolysisTumor Cells, CulturedTwist-Related Protein 1ConceptsEpithelial ovarian cancer stem cellsEpithelial-mesenchymal transitionCancer stem cellsMesenchymal-epithelial transitionEOC stem cellsStem cellsTwist-1Differentiation processEpithelial cancer stem cellsSpecific cell typesEpithelial cancer cellsSpheroid-forming cellsProteasomal degradationEpithelial stem cellsMolecular mechanismsCell typesProgenitor cellsMetastasis processCancer metastasisCancer cellsDifferentiationMetastatic potentialAdditional signalsCellsCritical process