2023
Monitoring Treatment Response, Early Recurrence, and Survival in Uterine Serous Carcinoma and Carcinosarcoma Patients Using Personalized Circulating Tumor DNA Biomarkers
Bellone S, McNamara B, Mutlu L, Demirkiran C, Hartwich T, Harold J, Yang-Hartwich Y, Siegel E, Santin A. Monitoring Treatment Response, Early Recurrence, and Survival in Uterine Serous Carcinoma and Carcinosarcoma Patients Using Personalized Circulating Tumor DNA Biomarkers. International Journal Of Molecular Sciences 2023, 24: 8873. PMID: 37240216, PMCID: PMC10219151, DOI: 10.3390/ijms24108873.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCarcinosarcomaCirculating Tumor DNACystadenocarcinoma, SerousFemaleHumansMutationNeoplasm Recurrence, LocalUterine NeoplasmsConceptsUterine serous carcinomaCS patientsEarly recurrenceDroplet digital polymerase chain reactionCA 125Serous carcinomaCtDNA testingTime of surgeryTime of recurrenceReliable tumor biomarkersTumour DNA biomarkersCarcinosarcoma patientsUSC patientsRecurrent diseaseOccult diseaseOverall survivalEndometrial cancerAggressive variantInitial treatmentRecurrent tumorsResidual tumorClinical findingsTreatment courseTreatment trialsPIK3CA mutationsUterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor
McNamara B, Harold J, Manavella D, Bellone S, Mutlu L, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Yang K, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Burton E, Inagaki H, Albers A, Zhang C, Bollag G, Schlessinger J, Santin A. Uterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor. Gynecologic Oncology 2023, 172: 65-71. PMID: 36958197, PMCID: PMC10192120, DOI: 10.1016/j.ygyno.2023.03.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFemaleGene AmplificationHumansLeiomyosarcomaMAP Kinase Kinase 4MiceMice, SCIDNeoplasm Recurrence, LocalPelvic NeoplasmsUterine NeoplasmsConceptsUterine leiomyosarcomaPDX modelsGain of functionMedian overall survivalPhase I trialOral gavage dailyVivo activityTumor growth inhibitionTumor volume differencesTumor cell proliferationOverall survivalTolerable toxicityI trialOral treatmentTreatment cohortsGavage dailyAggressive tumorsSCID miceULMS patientsPK studiesTumor samplesWestern blotCell proliferationControl vehicleLeiomyosarcoma
2021
Progression of Cystadenoma to Mucinous Borderline Ovarian Tumor in Young Females: Case Series and Literature Review
Beroukhim G, Ozgediz D, Cohen PJ, Hui P, Morotti R, Schwartz PE, Yang-Hartwich, Vash-Margita A. Progression of Cystadenoma to Mucinous Borderline Ovarian Tumor in Young Females: Case Series and Literature Review. Journal Of Pediatric And Adolescent Gynecology 2021, 35: 359-367. PMID: 34843973, DOI: 10.1016/j.jpag.2021.11.003.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentChildCystadenoma, MucinousFemaleHumansNeoplasm Recurrence, LocalOvarian CystsOvarian NeoplasmsRetrospective StudiesConceptsMucinous borderline ovarian tumorsBorderline ovarian tumorsOvarian tumorsYale-New Haven HospitalRetrospective chart reviewBenign ovarian tumorsBenign ovarian lesionsRate of recurrenceNew Haven HospitalAbdominal painPreoperative characteristicsChart reviewDisease recurrenceRecurrent cystsCase seriesChief complaintClinical presentationClinicopathologic featuresFemale patientsMucinous cystadenomaOvarian cystsOvarian lesionsTumor stageAdolescent patientsSubsequent surveillancePersonalized models of heterogeneous 3D epithelial tumor microenvironments: Ovarian cancer as a model
Horst EN, Bregenzer ME, Mehta P, Snyder CS, Repetto T, Yang-Hartwich Y, Mehta G. Personalized models of heterogeneous 3D epithelial tumor microenvironments: Ovarian cancer as a model. Acta Biomaterialia 2021, 132: 401-420. PMID: 33940195, PMCID: PMC8969826, DOI: 10.1016/j.actbio.2021.04.041.Peer-Reviewed Original ResearchMeSH KeywordsExtracellular MatrixFemaleHumansNeoplasm Recurrence, LocalOvarian NeoplasmsPrecision MedicineTumor MicroenvironmentConceptsOptimal adjuvant treatmentTumor microenvironmentOvarian cancerCancer modelAdverse clinical outcomesHeterogeneous patient populationMinimal residual diseaseDifferent tumor locationsConventional cancer treatmentsEpithelial tumor microenvironmentModels of cancerAdjuvant treatmentDurable responsesTreatment failureClinical outcomesResidual diseasePatient populationTumor locationDisease progressionEffective therapyFundamental cancer biologyDiverse tumor microenvironmentsIndividual patientsSame patientPatient biopsies
2018
Mutational landscape of primary, metastatic, and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors
Li C, Bonazzoli E, Bellone S, Choi J, Dong W, Menderes G, Altwerger G, Han C, Manzano A, Bianchi A, Pettinella F, Manara P, Lopez S, Yadav G, Riccio F, Zammataro L, Zeybek B, Yang-Hartwich Y, Buza N, Hui P, Wong S, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Zizioli V, Odicino F, Pecorelli S, Ardighieri L, Silasi DA, Litkouhi B, Ratner E, Azodi M, Huang GS, Schwartz PE, Lifton RP, Schlessinger J, Santin AD. Mutational landscape of primary, metastatic, and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 116: 619-624. PMID: 30584090, PMCID: PMC6329978, DOI: 10.1073/pnas.1814027116.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAzepinesBRCA1 ProteinBRCA2 ProteinCell Line, TumorClass I Phosphatidylinositol 3-KinasesFemaleHumansMiceMutationNeoplasm MetastasisNeoplasm Recurrence, LocalOvarian NeoplasmsProteinsProto-Oncogene Proteins c-mycTriazolesTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsOvarian cancerWhole-exome sequencingC-myc amplificationRecurrent tumorsPrimary tumorBET inhibitorsChemotherapy-resistant diseaseRecurrent ovarian cancerLethal gynecologic malignancyBilateral ovarian cancerChemotherapy-resistant tumorsPrimary metastatic tumorsMutational landscapeSomatic mutationsFresh-frozen tumorsGynecologic malignanciesMetastatic tumorsPrimary cell linesC-MYC gainPIK3CA amplificationTranscoelomic metastasisTherapeutic targetPatientsMetastatic abilityTumors
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
Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence
Sumi NJ, Lima E, Pizzonia J, Orton SP, Craveiro V, Joo W, Holmberg JC, Gurrea M, Yang-Hartwich Y, Alvero A, Mor G. Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence. Journal Of Visualized Experiments 2014, 51815. PMID: 25407815, PMCID: PMC4353409, DOI: 10.3791/51815.Peer-Reviewed Original ResearchConceptsRecurrent ovarian cancerOvarian cancerVisible light rangeAnatomical locationOptical imaging platformAvailable chemotherapy agentsLethal gynecologic malignancyOvarian cancer recurrenceEpithelial ovarian cancerNovel therapy optionsAppropriate animal modelsMultiple angular positionsLight rangeIdentification of tumorsGynecologic malignanciesRecurrent diseaseSurgical debulkingChemoresistant diseaseCombination chemotherapyClinical profileNon-invasive imagingTherapy optionsCancer recurrenceX-rayChemotherapy agents
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