2022
Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor
Manavella D, McNamara B, Harold J, Bellone S, Hartwich T, Yang-Hartwich Y, Mutlu L, Zipponi M, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Dottino P, Choi J, Alexandrov L, Buza N, Hui P, Santin A. Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor. Gynecologic Oncology 2022, 169: 98-105. PMID: 36525930, PMCID: PMC9925406, DOI: 10.1016/j.ygyno.2022.12.003.Peer-Reviewed Original ResearchConceptsHomologous recombination deficiencyCS cell linesCell linesWestern blotKinase inhibitorsOverall animal survivalProtein expressionDose-dependent increaseDose-dependent inhibitionCarcinosarcoma cell lineTumor growth inhibitionCaspase-3 expressionEndometrioid histologyAggressive malignancyUterine carcinosarcomaCS patientsPreclinical activityClinical trialsEpithelial componentAnimal survivalXenograftsApoptosis markersRecombination deficiencyP-ATRP-Chk1Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma
Harold J, Bellone S, Manavella D, Mutlu L, McNamara B, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Santin A. Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma. Gynecologic Oncology 2022, 168: 157-165. PMID: 36442427, PMCID: PMC9797429, DOI: 10.1016/j.ygyno.2022.11.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtaxia Telangiectasia Mutated ProteinsFemaleHumansLeiomyosarcomaMiceMice, SCIDMutationUterine NeoplasmsX-linked Nuclear ProteinConceptsPatient-derived xenograftsUterine leiomyosarcomaVivo activityVehicle control treatmentMedian overall survivalTumor volume differencesOral scheduleWestern blot analysisOverall survivalOral gavageAggressive malignancyPDX modelsClinical trialsSCID miceTumor measurementsULMS patientsSignificant growth inhibitionNovel ATR inhibitorTumor samplesSignificant toxicityWestern blotKinase inhibitorsATRX mutationsGene mutationsControl vehicleSynergistic activity of neratinib in combination with olaparib in uterine serous carcinoma overexpressing HER2/neu
Yadav G, Roque DM, Bellone S, Manavella DD, Hartwich TMP, Zipponi M, Harold J, Tymon-Rosario J, Mutlu L, Altwerger G, Menderes G, Ratner E, Buza N, Hui P, Huang GS, Andikyan V, Clark M, Azodi M, Schwartz PE, Alexandrov LB, Santin AD. Synergistic activity of neratinib in combination with olaparib in uterine serous carcinoma overexpressing HER2/neu. Gynecologic Oncology 2022, 166: 351-357. PMID: 35641325, DOI: 10.1016/j.ygyno.2022.05.021.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaHER2/neu expressionHER2/neuCombination of olaparibUSC xenograftsUSC cell linesNeu expressionSerous carcinomaLow HER2/neu expressionHER2/neu 3Cell linesHER2/neu gene amplificationNovel therapeutic optionsPolymerase inhibitor olaparibNeu gene amplificationDurable growth inhibitionNeratinib treatmentUSC cellsUSC patientsEndometrial cancerAggressive variantTherapeutic optionsPoor prognosisHER2/Single agent
2021
Minimal uterine serous carcinoma and endometrial polyp: a close clinicopathological relationship
Assem H, Rottmann D, Finkelstein A, Wang M, Ratner E, Santin AD, Buza N, Hui P. Minimal uterine serous carcinoma and endometrial polyp: a close clinicopathological relationship. Human Pathology 2021, 118: 1-8. PMID: 34508766, DOI: 10.1016/j.humpath.2021.09.001.Peer-Reviewed Original ResearchMeSH KeywordsAgedCystadenocarcinoma, SerousEndometrial NeoplasmsFemaleHumansMiddle AgedPolypsUterine NeoplasmsConceptsMinimal uterine serous carcinomaEndometrial polypsUterine serous carcinomaSerous carcinomaHigh stage patientsLow stage patientsPelvic washing cytologyAdvanced stage diseaseEndometrial serous carcinomaHigher stage diseaseLower tumor stageClinical outcome assessmentClose topographic relationshipBackground endometriumExtrauterine diseaseExtrauterine spreadStage diseaseExcellent prognosisLymphovascular invasionClinicopathological relationshipWashing cytologyTumor stageHigh riskPatientsLarge seriesDHES0815A, a novel antibody-drug conjugate targeting HER2/neu, is highly active against uterine serous carcinomas in vitro and in vivo
Tymon-Rosario J, Bonazzoli E, Bellone S, Manzano A, Pelligra S, Guglielmi A, Gnutti B, Nagarkatti N, Zeybek B, Manara P, Zammataro L, Harold J, Mauricio D, Buza N, Hui P, Altwerger G, Menderes G, Ratner E, Clark M, Andikyan V, Huang GS, Silasi DA, Azodi M, Schwartz PE, Santin AD. DHES0815A, a novel antibody-drug conjugate targeting HER2/neu, is highly active against uterine serous carcinomas in vitro and in vivo. Gynecologic Oncology 2021, 163: 334-341. PMID: 34452746, PMCID: PMC8722447, DOI: 10.1016/j.ygyno.2021.08.014.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedBenzodiazepinesBystander EffectCell Line, TumorCystadenocarcinoma, SerousDrug Resistance, NeoplasmFemaleHumansImmunoconjugatesMiddle AgedPrimary Cell CultureReceptor, ErbB-2TrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsHER2/neuPrimary USC cell linesUSC cell linesUterine serous carcinomaSerous carcinomaHER2/Cell linesBystander killingHER2/neu protein expressionHER2/neu overexpressionProtein expressionNovel treatment optionsAggressive histologic variantNeu protein expressionHER2 protein expressionC-erbB2 gene amplificationSignificant bystander killingUSC xenograftsEndometrial cancerNegative tumorsPoor prognosisPositive tumorsTreatment optionsPreclinical activityHistologic variants
2020
Heterozygous/dispermic complete mole confers a significantly higher risk for post-molar gestational trophoblastic disease
Zheng XZ, Qin XY, Chen SW, Wang P, Zhan Y, Zhong PP, Buza N, Jin YL, Wu BQ, Hui P. Heterozygous/dispermic complete mole confers a significantly higher risk for post-molar gestational trophoblastic disease. Modern Pathology 2020, 33: 1979-1988. PMID: 32404958, DOI: 10.1038/s41379-020-0566-4.Peer-Reviewed Original ResearchMeSH KeywordsAdultFemaleGenotypeHumansHydatidiform MoleHydatidiform Mole, InvasiveMiddle AgedPregnancyUterine NeoplasmsYoung AdultConceptsNon-molar gestationsGestational trophoblastic diseaseTrophoblastic diseaseHigh riskGestational trophoblastic neoplasiaProducts of conceptionPatient demographicsClinical followClinical outcomesGynecology HospitalTrophoblastic neoplasiaBeijing ObstetricsFIGO criteriaChinese patientsClinical prognosisPatient managementLarge cohortGestationMolar gestationDiseaseGenetic abnormalitiesChromosomal monosomyChromosomal aneuploidyHydatidiformUniparental disomyExtragonadal Yolk Sac Tumor Limited to the Myometrium: Report of a Case With Potential Fertility Preservation and Molecular Analysis Suggesting Germ Cell Origin
Simpson S, Simoni M, Hui P, Taylor H, Buza N. Extragonadal Yolk Sac Tumor Limited to the Myometrium: Report of a Case With Potential Fertility Preservation and Molecular Analysis Suggesting Germ Cell Origin. International Journal Of Gynecological Pathology 2020, 39: 247-253. PMID: 31033797, DOI: 10.1097/pgp.0000000000000601.Peer-Reviewed Original ResearchConceptsYolk sac tumorExtragonadal yolk sac tumorGerm cell originFuture fertilityIntraoperative frozen section evaluationCell originPatient's strong desirePostpubertal female patientsEvidence of diseaseFrozen section evaluationMarked nuclear atypiaClear treatment algorithmRare malignant neoplasmHigh-grade malignancyEosinophilic hyaline globulesNext-generation sequencing resultsAdjuvant chemotherapySurgical stagingAbdominal myomectomyNulligravid womenIrregular bleedingUterine closureWedge resectionYounger patientsFemale patientsMolecular and clinicopathologic characterization of intravenous leiomyomatosis
Ordulu Z, Chai H, Peng G, McDonald AG, De Nictolis M, Garcia-Fernandez E, Hardisson D, Prat J, Li P, Hui P, Oliva E, Buza N. Molecular and clinicopathologic characterization of intravenous leiomyomatosis. Modern Pathology 2020, 33: 1844-1860. PMID: 32341498, PMCID: PMC7483566, DOI: 10.1038/s41379-020-0546-8.Peer-Reviewed Original ResearchConceptsIntravenous leiomyomatosisAggressive clinical behaviorClinical behaviorArray comparative genomic hybridizationCyclin D1Uterine smooth muscle tumorsSmooth muscle tumorsSmooth muscle proliferationRecurrent chromosome alterationsCommon genetic alterationsFH immunohistochemistryClinicopathologic characterizationImmunohistochemical findingsMesenchymal tumorsMuscle tumorsBenign appearanceMuscle proliferationUterine leiomyomaGroup 1Group 3Nonneoplastic tissuesIndex scoreVascular morphologyProtein expressionComparative genomic hybridization
2019
In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma
Han C, Perrone E, Zeybek B, Bellone S, Tymon-Rosario J, Altwerger G, Menderes G, Feinberg J, Haines K, Muller Karger ME, Bianchi A, Zammataro L, Manzano A, Bonazzoli E, Manara P, Buza N, Hui P, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Lopez S, Santin AD. In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma. Gynecologic Oncology 2019, 156: 430-438. PMID: 31839338, DOI: 10.1016/j.ygyno.2019.11.018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmCamptothecinCell Adhesion MoleculesCell Line, TumorCystadenocarcinoma, SerousFemaleFlow CytometryHumansImmunoconjugatesImmunohistochemistryMiceMice, SCIDMolecular Targeted TherapyRandom AllocationTissue Array AnalysisUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaCell surface antigen 2Sacituzumab govitecanTrop-2 expressionTrop-2Serous carcinomaAntigen 2Advanced/recurrent diseasePrimary uterine serous carcinomaResistant human tumorsSignificant bystander killingUSC patientsUSC xenograftsRecurrent diseaseClinical responseEndometrial cancerAggressive variantPoor prognosisPreclinical activityPrimary tumorIntravenous administrationClinical developmentUSC samplesActive metaboliteSN-38HER2 testing of gynecologic carcinosarcomas: tumor stratification for potential targeted therapy
Rottmann D, Snir OL, Wu X, Wong S, Hui P, Santin AD, Buza N. HER2 testing of gynecologic carcinosarcomas: tumor stratification for potential targeted therapy. Modern Pathology 2019, 33: 118-127. PMID: 31477811, DOI: 10.1038/s41379-019-0358-x.Peer-Reviewed Original ResearchConceptsEndometrial serous carcinomaHER2-positive tumorsSerous carcinomaSarcoma componentHER2 statusGynecologic carcinosarcomaHER2 expression/amplificationRecent phase II clinical trialPhase II clinical trialCarboplatin-paclitaxel chemotherapyEquivocal HER2 expressionProgression-free survivalAppropriate patient selectionExpression/amplificationFemale genital tractMembranous staining patternHER2 protein expressionHER2 immunohistochemical scoresUterine primaryDismal prognosisPatient selectionCarcinoma componentMixed carcinomasHER2 expressionClinical trialsPrecision genotyping diagnosis of lung tumors with trophoblastic morphology in young women
Buza N, Baine I, Hui P. Precision genotyping diagnosis of lung tumors with trophoblastic morphology in young women. Modern Pathology 2019, 32: 1271-1280. PMID: 31028360, DOI: 10.1038/s41379-019-0275-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultChoriocarcinomaFemaleGenotypeHumansLung NeoplasmsMiddle AgedPregnancyTrophoblastic NeoplasmsUterine NeoplasmsConceptsGestational choriocarcinomaLung carcinomaLung massClinical historyLung tumorsGestational originSerum beta-hCG levelsYoung womenTrophoblastic differentiationMetastatic gestational choriocarcinomaSerum beta-hCGBeta-hCG levelsEvidence of diseaseUnique diagnostic challengePrimary lung carcinomaGestational trophoblastic neoplasiaDifferent chemotherapeutic regimensDifferent primary sitesWedge resectionBeta-hCGFemale patientsMetastatic choriocarcinomaThird patientChemotherapeutic regimensImmunophenotypical featuresPaternal uniparental isodisomy of tyrosine hydroxylase locus at chromosome 11p15.4: spectrum of phenotypical presentations simulating hydatidiform moles
Buza N, McGregor SM, Barroilhet L, Zheng X, Hui P. Paternal uniparental isodisomy of tyrosine hydroxylase locus at chromosome 11p15.4: spectrum of phenotypical presentations simulating hydatidiform moles. Modern Pathology 2019, 32: 1180-1188. PMID: 30952972, DOI: 10.1038/s41379-019-0266-0.Peer-Reviewed Original ResearchMeSH KeywordsAbortion, MissedAdultAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorChromosomes, Human, Pair 11CyclophosphamideDactinomycinEtoposideFemaleGenetic LociGenetic Predisposition to DiseaseHumansHydatidiform MoleMaleMethotrexatePhenotypePregnancyTreatment OutcomeTyrosine 3-MonooxygenaseUniparental DisomyUterine NeoplasmsVincristineConceptsPaternal uniparental isodisomyAbnormal trophoblastic proliferationCases of gestationUneventful clinical courseAggressive clinical behaviorUniparental isodisomyTyrosine hydroxylase locusMultiagent chemotherapyClinical courseFirst trimesterClinical complicationsImmunohistochemical featuresClinical behaviorMissed abortionAbnormal gestationsTyrosine hydroxylasePatientsTrophoblastic proliferationVillous cytotrophoblastsStromal cellsPhenotypical presentationChorionic villiGenetic conditionsP57 expressionGestation
2018
Gestational Trophoblastic Tumors: A Timely Review of Diagnostic Pathology
Hui P. Gestational Trophoblastic Tumors: A Timely Review of Diagnostic Pathology. Archives Of Pathology & Laboratory Medicine 2018, 143: 65-74. PMID: 30407075, DOI: 10.5858/arpa.2018-0234-ra.Peer-Reviewed Original ResearchMeSH KeywordsChoriocarcinomaFemaleGestational Trophoblastic DiseaseHumansPlacentaPregnancyTrophoblastic Tumor, Placental SiteUterine NeoplasmsConceptsGestational trophoblastic tumorsTrophoblastic tumorPersistent gestational trophoblastic neoplasiaPlacental site trophoblastic tumorAtypical placental site noduleEarly chemotherapeutic interventionPlacental site noduleEpithelioid trophoblastic tumorGestational trophoblastic neoplasiaClinical featuresGestational choriocarcinomaTrophoblastic neoplasiaHistologic characteristicsPathologic diagnosisClinical managementPrecursor lesionsHigh indexClinical practiceAccurate diagnosisTumorsChemotherapeutic interventionSurveillance programDistinct entityMolecular biomarkersDiagnostic recognitionInhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer
Bonazzoli E, Predolini F, Cocco E, Bellone S, Altwerger G, Menderes G, Zammataro L, Bianchi A, Pettinella F, Riccio F, Han C, Yadav G, Lopez S, Manzano A, Manara P, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Schlessinger J, Santin AD. Inhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer. Clinical Cancer Research 2018, 24: 4845-4853. PMID: 29941483, PMCID: PMC6168417, DOI: 10.1158/1078-0432.ccr-18-0864.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntineoplastic AgentsApoptosisAurora Kinase AAurora Kinase BAzepinesCell Line, TumorCell ProliferationCystadenocarcinoma, SerousDose-Response Relationship, DrugEndometrial NeoplasmsExome SequencingFemaleGene Expression Regulation, NeoplasticHumansMiceMiddle AgedPhosphorylationPrimary Cell CultureProteinsProto-Oncogene Proteins c-mycTriazolesUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaPrimary USC cell linesUSC cell linesC-myc expressionCell linesC-MycChemotherapy-resistant diseaseQRT-PCRHigh c-myc expressionDose-dependent decreaseDose-dependent increasePotential therapeutic targetEffective therapeutic agentMouse xenograft modelClin Cancer ResFresh frozen tumor tissueC-myc gene amplificationUSC xenograftsEndometrial cancerAggressive variantSerous carcinomaWhole-exome sequencing studiesClinical studiesConcentrations/dosesXenograft modelRandomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu.
Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers SK, Secord AA, Havrilesky L, O'Malley DM, Backes F, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi KS, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu. Journal Of Clinical Oncology 2018, 36: 2044-2051. PMID: 29584549, DOI: 10.1200/jco.2017.76.5966.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2Progression-free survivalUterine serous carcinomaRecurrent uterine serous carcinomaMedian progression-free survivalRandomized phase II trialEpidermal growth factor receptor 2Phase II trialGrowth factor receptor 2Serous carcinomaHER2/neuFactor receptor 2II trialTreatment armsReceptor 2Stage IIIHER2/neu-positive diseaseOne-sided log-rank testMethods Eligible patientsPrimary end pointPrimary stage IIIUnexpected safety signalsLog-rank testHumanized monoclonal antibodyEligible patientsMicroRNA signatures discriminate between uterine and ovarian serous carcinomas
Hui P, Gysler SM, Uduman M, Togun TA, Prado DE, Brambs CE, Nallur S, Schwartz PE, Rutherford TJ, Santin AD, Weidhaas JB, Ratner ES. MicroRNA signatures discriminate between uterine and ovarian serous carcinomas. Human Pathology 2018, 76: 133-140. PMID: 29518404, DOI: 10.1016/j.humpath.2018.02.019.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorCarcinomaDiagnosis, DifferentialFemaleGene Expression ProfilingGenetic Predisposition to DiseaseHumansMicroRNAsMiddle AgedNeoplasm GradingNeoplasms, Cystic, Mucinous, and SerousOligonucleotide Array Sequence AnalysisOvarian NeoplasmsPhenotypePredictive Value of TestsReproducibility of ResultsRetrospective StudiesTranscriptomeUterine NeoplasmsConceptsHigh-grade serous carcinomaOvarian serous carcinomaSerous carcinomaOvarian malignancyPrimary ovarian high-grade serous carcinomaOvarian high-grade serous carcinomaMiRNA signatureEndometrial serous carcinomaHigh-grade ovarian serous carcinomaUterine serous carcinomaEndometrial counterpartOvarian primaryTaqMan Low Density Array technologySynchronous primariesEndometrial cancerMetastatic tumorsCarcinomaPrimary siteSignature panelPathological determinationMicroRNA signatureSignificant discriminatory powerCancer cellsMalignancyLineage characteristics
2017
SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine and Ovarian Carcinosarcoma with HER2/Neu Expression
Menderes G, Bonazzoli E, Bellone S, Black J, Predolini F, Pettinella F, Masserdotti A, Zammataro L, Altwerger G, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Azodi M, Schwartz PE, Santin AD. SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine and Ovarian Carcinosarcoma with HER2/Neu Expression. Clinical Cancer Research 2017, 23: 5836-5845. PMID: 28679774, PMCID: PMC5626613, DOI: 10.1158/1078-0432.ccr-16-2862.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAnimalsAntibody-Dependent Cell CytotoxicityCarcinosarcomaCell Line, TumorCell ProliferationDuocarmycinsFemaleGene Expression Regulation, NeoplasticHumansImmunoconjugatesIndolesMaytansineMiceOvarian NeoplasmsPyrrolidinonesReceptor, ErbB-2TrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsAntibody-dependent cellular cytotoxicityHER2/neu expressionHER2/neu 3T-DM1Antibody-drug conjugatesCS cell linesNeu expressionEffector cellsHigh HER2/neu expressionNeu 3HER2-targeting antibody-drug conjugateCell linesBystander killingPatient-derived xenograft modelsNovel HER2-targeting antibody-drug conjugateAggressive gynecologic malignancyHigh HER2 expressionEffective antibody-drug conjugatesHER2/neuClin Cancer ResGynecologic malignanciesOvarian carcinosarcomaHER2 expressionTrastuzumab emtansineSYD985Hydatidiform Moles: Genetic Basis and Precision Diagnosis
Hui P, Buza N, Murphy KM, Ronnett BM. Hydatidiform Moles: Genetic Basis and Precision Diagnosis. Annual Review Of Pathology Mechanisms Of Disease 2017, 12: 449-485. PMID: 28135560, DOI: 10.1146/annurev-pathol-052016-100237.Peer-Reviewed Original Research
2016
Mutational landscape of uterine and ovarian carcinosarcomas implicates histone genes in epithelial–mesenchymal transition
Zhao S, Bellone S, Lopez S, Thakral D, Schwab C, English DP, Black J, Cocco E, Choi J, Zammataro L, Predolini F, Bonazzoli E, Bi M, Buza N, Hui P, Wong S, Abu-Khalaf M, Ravaggi A, Bignotti E, Bandiera E, Romani C, Todeschini P, Tassi R, Zanotti L, Odicino F, Pecorelli S, Donzelli C, Ardighieri L, Facchetti F, Falchetti M, Silasi DA, Ratner E, Azodi M, Schwartz PE, Mane S, Angioli R, Terranova C, Quick CM, Edraki B, Bilgüvar K, Lee M, Choi M, Stiegler AL, Boggon TJ, Schlessinger J, Lifton RP, Santin AD. Mutational landscape of uterine and ovarian carcinosarcomas implicates histone genes in epithelial–mesenchymal transition. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 12238-12243. PMID: 27791010, PMCID: PMC5087050, DOI: 10.1073/pnas.1614120113.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overCarcinosarcomaClass I Phosphatidylinositol 3-KinasesDNA-Binding ProteinsEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHistonesHumansMiddle AgedMutationOvarian NeoplasmsPTEN PhosphohydrolaseTelomeraseTumor Suppressor Protein p53Uterine NeoplasmsConceptsEpithelial-mesenchymal transitionWhole-exome sequencingHistone gene clusterMutational landscapeStable transgenic expressionExcess of mutationsMultiregion whole-exome sequencingHistone genesEvolutionary historyPhylogenetic relationshipsGene clusterHistone H2AChromosome segmentsSeparate lineagesCancer genesGenetic landscapeUterine serous carcinoma cell linesTransgenic expressionGenesCarcinoma cell linesGene TP53Frequent amplificationFrequent deletionsChromosome 6pInvasive propertiesSYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine Serous Carcinoma with HER2/Neu Expression
Black J, Menderes G, Bellone S, Schwab CL, Bonazzoli E, Ferrari F, Predolini F, De Haydu C, Cocco E, Buza N, Hui P, Wong S, Lopez S, Ratner E, Silasi DA, Azodi M, Litkouhi B, Schwartz PE, Goedings P, Beusker PH, van der Lee MM, Timmers CM, Dokter WH, Santin AD. SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine Serous Carcinoma with HER2/Neu Expression. Molecular Cancer Therapeutics 2016, 15: 1900-1909. PMID: 27256376, DOI: 10.1158/1535-7163.mct-16-0163.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsBystander EffectCathepsin BCell Line, TumorCell SurvivalClass I Phosphatidylinositol 3-KinasesCystadenocarcinoma, SerousDisease Models, AnimalDuocarmycinsFemaleGene ExpressionHumansImmunoconjugatesIndolesMiceMiddle AgedMutationPhosphatidylinositol 3-KinasesPyrrolidinonesReceptor, ErbB-2Survival AnalysisUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaAntibody-dependent cellular cytotoxicityHER2/neu expressionAntibody-drug conjugatesT-DM1Neu expressionHER2-targeting antibody-drug conjugateNovel antibody-drug conjugateNovel HER2-targeting antibody-drug conjugatePrimary USC cell linesHigh HER2 expressionHER2/neu oncogeneHER2/neuMouse xenograft modelUSC cell linesFlow cytometry assayEndometrial cancerSerous carcinomaHER2 expressionTrastuzumab emtansineClinical studiesCellular cytotoxicitySYD985Aggressive formExpress HER2