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-38
2018
Inhibition 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 patients
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 emtansineSYD985
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 HER2Dual CCNE1/PIK3CA targeting is synergistic in CCNE1-amplified/PIK3CA-mutated uterine serous carcinomas in vitro and in vivo
Cocco E, Lopez S, Black J, Bellone S, Bonazzoli E, Predolini F, Ferrari F, Schwab CL, Menderes G, Zammataro L, Buza N, Hui P, Wong S, Zhao S, Bai Y, Rimm DL, Ratner E, Litkouhi B, Silasi DA, Azodi M, Schwartz PE, Santin AD. Dual CCNE1/PIK3CA targeting is synergistic in CCNE1-amplified/PIK3CA-mutated uterine serous carcinomas in vitro and in vivo. British Journal Of Cancer 2016, 115: 303-311. PMID: 27351214, PMCID: PMC4973158, DOI: 10.1038/bjc.2016.198.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorClass I Phosphatidylinositol 3-KinasesCyclin EDNA Copy Number VariationsFemaleGene Knockdown TechniquesHeterograftsHumansIn Situ Hybridization, FluorescenceIn Vitro TechniquesMiceMutationOncogene ProteinsPhosphatidylinositol 3-KinasesRNA, MessengerTissue Array AnalysisUterine NeoplasmsConceptsUterine serous carcinomaSerous carcinomaTumor growthCyclin E1 (CCNE1) gene amplificationRecurrent uterine serous carcinomaPrimary USC cell linesNovel therapeutic optionsSingle-agent treatmentIdeal therapeutic targetUSC cell linesCyclin E1 expressionUSC patientsUSC xenograftsInhibited cell growthCell cycle analysisAggressive variantTherapeutic optionsCCNE1 amplificationEndometrial tumorsCYC065Therapeutic targetClinical optionPIK3CA driver mutationsDriver mutationsXenograftsEfficacy and tolerability of combination cisplatin and ifosfamide chemotherapy with vaginal cuff brachytherapy in the first line treatment of uterine carcinosarcoma.
Abu-Khalaf MM, Raza MA, Hatzis C, Wang H, Lin K, Higgins S, Ratner E, Silasi DA, Azodi M, Rutherford TJ, Santin AD, Schwartz PE. Efficacy and tolerability of combination cisplatin and ifosfamide chemotherapy with vaginal cuff brachytherapy in the first line treatment of uterine carcinosarcoma. European Journal Of Gynaecological Oncology 2016, 37: 199-203. PMID: 27172745.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnemiaAntineoplastic Combined Chemotherapy ProtocolsBrachytherapyCarcinosarcomaChemoradiotherapyCisplatinDisease-Free SurvivalFemaleHumansIfosfamideMesnaMiddle AgedNeoplasm StagingNeutropeniaProtective AgentsRetrospective StudiesTreatment OutcomeUterine NeoplasmsConceptsVaginal cuff brachytherapyProgression-free survivalFirst-line treatmentOverall survivalUterine carcinosarcomaStage ILine treatmentStage IIIDay 1Anemia grade 1Most common toxicitiesNeutropenia grade 3Cycles of cisplatinMedian overall survivalStage IV diseaseCommon toxicitiesMedian followTreatment discontinuationFree survivalPatient withdrawalCombination cisplatinDose modificationMedian ageRetrospective studyGrade 3
2015
Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo
Lopez S, Cocco E, Black J, Bellone S, Bonazzoli E, Predolini F, Ferrari F, Schwab CL, English DP, Ratner E, Silasi DA, Azodi M, Schwartz PE, Terranova C, Angioli R, Santin AD. Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo. Molecular Cancer Therapeutics 2015, 14: 2519-2526. PMID: 26333383, PMCID: PMC4636465, DOI: 10.1158/1535-7163.mct-15-0383.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsCell CycleCell Line, TumorCell SurvivalClass I Phosphatidylinositol 3-KinasesCystadenocarcinoma, SerousDose-Response Relationship, DrugDrug SynergismFemaleGene AmplificationHumansImidazolesImmunoblottingMice, SCIDMutationOxazepinesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationQuinolinesReceptor, ErbB-2Uterine NeoplasmsXenograft Model Antitumor AssaysConceptsHER2/neu gene amplificationNeu gene amplificationUSC xenograftsUterine serous carcinomaGene amplificationUterine serous carcinoma cell linesSingle-agent therapyNovel therapeutic optionsWild-type PIK3CADose-dependent increaseIdeal therapeutic targetUSC cell linesCell linesDose-dependent declineFlow cytometry assayG0-G1 phaseCell cycle distributionOncogenic PIK3CA mutationsPercentage of cellsUSC patientsEndometrial cancerAggressive variantSerous carcinomaTherapeutic optionsCarcinoma cell linesSolitomab, an EpCAM/CD3 bispecific antibody construct (BiTE®), is highly active against primary uterine and ovarian carcinosarcoma cell lines in vitro
Ferrari F, Bellone S, Black J, Schwab CL, Lopez S, Cocco E, Bonazzoli E, Predolini F, Menderes G, Litkouhi B, Ratner E, Silasi DA, Azodi M, Schwartz PE, Santin AD. Solitomab, an EpCAM/CD3 bispecific antibody construct (BiTE®), is highly active against primary uterine and ovarian carcinosarcoma cell lines in vitro. Journal Of Experimental & Clinical Cancer Research 2015, 34: 123. PMID: 26474755, PMCID: PMC4609066, DOI: 10.1186/s13046-015-0241-7.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, BispecificAntigens, NeoplasmAntineoplastic AgentsCarcinosarcomaCD3 ComplexCell Adhesion MoleculesCell Line, TumorCell ProliferationCoculture TechniquesCytokinesCytotoxicity, ImmunologicDrug Resistance, NeoplasmEpithelial Cell Adhesion MoleculeFemaleFlow CytometryHumansKiller Cells, NaturalLymphocyte ActivationMiddle AgedOvarian NeoplasmsT-Lymphocytes, CytotoxicUterine NeoplasmsConceptsCS cell linesPeripheral blood lymphocytesT cellsEpCAM/CD3-bispecific antibodyCell linesT cell-mediated killingT-cell activation markersFlow cytometryCD3 bispecific antibodyChromium release assaysT cell proliferationCarcinosarcoma cell lineFlow cytometry assaySingle-chain antibody constructCS cellsPositive cell linesH 51CrOvarian carcinosarcomaPleural effusionActivation markersGynecologic tumorsPoor prognosisCS patientsRecurrent/Blood lymphocytesPIK3CA oncogenic mutations represent a major mechanism of resistance to trastuzumab in HER2/neu overexpressing uterine serous carcinomas
Black JD, Lopez S, Cocco E, Bellone S, Altwerger G, Schwab CL, English DP, Bonazzoli E, Predolini F, Ferrari F, Ratner E, Silasi DA, Azodi M, Schwartz PE, Santin AD. PIK3CA oncogenic mutations represent a major mechanism of resistance to trastuzumab in HER2/neu overexpressing uterine serous carcinomas. British Journal Of Cancer 2015, 113: 1020-1026. PMID: 26325104, PMCID: PMC4651122, DOI: 10.1038/bjc.2015.306.Peer-Reviewed Original ResearchConceptsUSC cell linesCell linesPIK3CA-mutated tumorsUterine serous carcinomaHER2/neuXenograft mouse modelOncogenic PIK3CA mutationsPrimary HER2Trastuzumab treatmentSerous carcinomaCarcinoma cell linesMechanisms of resistancePIK3CA mutationsTrastuzumab efficacyMouse modelTrastuzumabMouse xenograftsHER2Tumor growthMajor mechanismOncogenic mutationsWild-type cell linesSitu hybridisationSolitomab, an EpCAM/CD3 bispecific antibody construct (BiTE), is highly active against primary uterine serous papillary carcinoma cell lines in vitro
Bellone S, Black J, English DP, Schwab CL, Lopez S, Cocco E, Bonazzoli E, Predolini F, Ferrari F, Ratner E, Silasi DA, Azodi M, Schwartz PE, Santin AD. Solitomab, an EpCAM/CD3 bispecific antibody construct (BiTE), is highly active against primary uterine serous papillary carcinoma cell lines in vitro. American Journal Of Obstetrics And Gynecology 2015, 214: 99.e1-99.e8. PMID: 26272866, PMCID: PMC4698047, DOI: 10.1016/j.ajog.2015.08.011.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, BispecificAntigens, NeoplasmAntineoplastic AgentsAscitic FluidCarcinoma, PapillaryCD3 ComplexCD4-Positive T-LymphocytesCell Adhesion MoleculesCell Line, TumorCell ProliferationCell SurvivalCoculture TechniquesCytokinesCytotoxicity, ImmunologicEpithelial Cell Adhesion MoleculeFemaleFlow CytometryHumansLymphocyte ActivationNeoplasms, Cystic, Mucinous, and SerousT-Lymphocytes, CytotoxicUterine NeoplasmsConceptsUterine serous carcinoma cell linesUterine serous carcinomaEpithelial cell adhesion moleculeCell adhesion molecule expressionCarcinoma cell linesChromium release assaysSerous carcinoma cellsPeripheral blood lymphocytesAdhesion molecule expressionCell adhesion moleculeEpithelial cell adhesion molecule (EpCAM) expressionSerous carcinomaAdhesion moleculesBlood lymphocytesMolecule expressionT cellsAscitic fluidCell linesTumor-associated T cellsT cell-mediated killingT-cell activation markersFlow cytometryTumor cellsCarcinoma cellsRobust immunologic responsesA Technique for Vascular Control During Robotic-assisted Laparoscopic Myomectomy
Donat LC, Menderes G, Tower AM, Azodi M. A Technique for Vascular Control During Robotic-assisted Laparoscopic Myomectomy. Journal Of Minimally Invasive Gynecology 2015, 22: 543. PMID: 25680685, DOI: 10.1016/j.jmig.2015.02.003.Peer-Reviewed Original ResearchConceptsRobotic-assisted myomectomyBlood lossVascular controlUterine vesselsVascular clipsUtero-ovarian vesselsUterine artery occlusionJehovah's Witness patientsExperienced laparoscopic surgeonsRobotic-assisted approachesArtery occlusionUterine arteriesBlood transfusionPeritoneal windowSurgical morbidityLaparoscopic myomectomyFertility preservationSymptomatic leiomyomasSubserosal injectionBulldog clampsMyomectomyRobotic myomectomyTemporary occlusionLaparoscopic surgeonsRobotic approachDacomitinib (PF-00299804), a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor, demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro
Zhu L, Lopez S, Bellone S, Black J, Cocco E, Zigras T, Predolini F, Bonazzoli E, Bussi B, Stuhmer Z, Schwab CL, English DP, Ratner E, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Santin AD. Dacomitinib (PF-00299804), a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor, demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro. Tumor Biology 2015, 36: 5505-5513. PMID: 25669172, PMCID: PMC5573583, DOI: 10.1007/s13277-015-3218-4.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaReceptor tyrosine kinase inhibitorsHER2/neu gene amplificationTyrosine kinase inhibitorsUSC cell linesNeu gene amplificationEndometrial cancerIrreversible pan-ErbB receptor tyrosine kinase inhibitorEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsEpidermal growth factor receptor 2Cell linesKinase inhibitorsEffect of dacomitinibStandard salvage chemotherapyGrowth factor receptor 2Serous endometrial cancerFlow cytometry-based assayHER2/neuFactor receptor 2Dose-dependent declineGene amplificationCell cycle distributionCytometry-based assayGrowth inhibitionComparison of Lymphedema Incidence Between 2 Lymphadenectomy Techniques in Patients With Uterine Cancer Undergoing Robotic Staging
Menderes G, Azodi M, Schwartz P, Silasi DA. Comparison of Lymphedema Incidence Between 2 Lymphadenectomy Techniques in Patients With Uterine Cancer Undergoing Robotic Staging. International Journal Of Gynecological Cancer 2015, 25: 160-165. PMID: 25386859, DOI: 10.1097/igc.0000000000000308.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma, Clear CellAdultAgedAged, 80 and overCarcinoma, EndometrioidCarcinosarcomaConnecticutCystadenocarcinoma, SerousEndometrial NeoplasmsFemaleFollow-Up StudiesHumansIncidenceLymph Node ExcisionLymph NodesLymphatic MetastasisLymphedemaMiddle AgedNeoplasm StagingPara-Aortic BodiesPelvic NeoplasmsPrognosisRoboticsUterine NeoplasmsConceptsSelective pelvic lymphadenectomyExternal iliac lymph nodesLower extremity lymphedemaStandard pelvic lymphadenectomyIliac lymph nodesPelvic lymphadenectomyLymph nodesLymphadenectomy groupRobotic stagingExtremity lymphedemaUterine cancerPara-aortic lymph nodesPelvic lymphadenectomy groupIncidence of lymphedemaMean operative timePelvic lymph nodesBody mass indexPostoperative hospitalizationSelective lymphadenectomyConsecutive patientsEndometrial cancerEndometrioid adenocarcinomaLymphedema incidenceMass indexOperative time
2014
Afatinib demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro and in vivo
Schwab CL, Bellone S, English DP, Roque DM, Lopez S, Cocco E, Nicoletti R, Bortolomai I, Bonazzoli E, Ratner E, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Santin AD. Afatinib demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro and in vivo. British Journal Of Cancer 2014, 111: 1750-1756. PMID: 25268372, PMCID: PMC4453741, DOI: 10.1038/bjc.2014.519.Peer-Reviewed Original ResearchMeSH KeywordsAdultAfatinibAgedAged, 80 and overAnimalsApoptosisCell CycleCell ProliferationCystadenocarcinoma, SerousEndometrial NeoplasmsFemaleHumansImmunoenzyme TechniquesIn Situ Hybridization, FluorescenceIn Vitro TechniquesMiceMice, SCIDMiddle AgedPhosphorylationQuinazolinesReceptor, ErbB-2Signal TransductionTumor Cells, CulturedUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaUSC cell linesHER2/neu gene amplificationNeu gene amplificationAfatinib exposureOverall survivalCell linesHER2/neu amplificationEfficacy of afatinibPrimary USC cell linesGrowth of HER2Treatment of HER2Serous endometrial cancerErbB tyrosine kinase inhibitorsHER2/neuTyrosine kinase inhibitorsGene amplificationFlow cytometry assayCell cycle distributionUSC xenograftsEndometrial cancerSerous carcinomaUterine cancerAggressive formTumor xenograftsT‐DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo
English DP, Bellone S, Schwab CL, Bortolomai I, Bonazzoli E, Cocco E, Buza N, Hui P, Lopez S, Ratner E, Silasi D, Azodi M, Schwartz PE, Rutherford TJ, Santin AD. T‐DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo. Cancer Medicine 2014, 3: 1256-1265. PMID: 24890382, PMCID: PMC4302675, DOI: 10.1002/cam4.274.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAgedAged, 80 and overAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsApoptosisCarcinomaCell Cycle CheckpointsCell ProliferationDisease Models, AnimalFemaleGene AmplificationGene ExpressionGene Expression Regulation, NeoplasticHumansImmunohistochemistryIn Situ Hybridization, FluorescenceMaytansineMiddle AgedReceptor, ErbB-2RNA, MessengerTrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaUSC cell linesNovel antibody-drug conjugateT-DM1USC xenograftsAntibody-drug conjugatesSerous carcinomaAntibody-dependent cell-mediated cytotoxicityEpidermal growth factor receptor 2Cell linesPrimary USC cell linesGrowth factor receptor 2Cell-mediated cytotoxicityChromium release assaysNovel treatment optionsHER2 protein overexpressionFactor receptor 2HER2 gene amplificationHER2 protein expressionC-erbB2 gene amplificationGene amplificationDisease refractoryPrimary HER2USC cellsUSC patients
2013
Tubulin‐β‐III overexpression by uterine serous carcinomas is a marker for poor overall survival after platinum/taxane chemotherapy and sensitivity to epothilones
Roque DM, Bellone S, English DP, Buza N, Cocco E, Gasparrini S, Bortolomai I, Ratner E, Silasi D, Azodi M, Rutherford TJ, Schwartz PE, Santin AD. Tubulin‐β‐III overexpression by uterine serous carcinomas is a marker for poor overall survival after platinum/taxane chemotherapy and sensitivity to epothilones. Cancer 2013, 119: 2582-2592. PMID: 23585021, PMCID: PMC3700638, DOI: 10.1002/cncr.28017.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCystadenocarcinoma, SerousDrug Resistance, NeoplasmEpothilonesFemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMiddle AgedNeoplasm StagingPaclitaxelPlatinum CompoundsPredictive Value of TestsPrognosisReal-Time Polymerase Chain ReactionTubulinTubulin ModulatorsUp-RegulationUterine NeoplasmsConceptsUterine serous carcinomaOvarian serous carcinomaOverall survivalSerous carcinomaP-glycoproteinClinical outcomesPaclitaxel resistanceTreatment of USCPlatinum/taxane chemotherapyPoor overall survivalFresh frozen tissue samplesReal-time polymerase chain reactionCell linesTaxane chemotherapyEndometrial cancerPoor outcomePoor prognosisPolymerase chain reactionFresh frozen tissueMedian inhibitory concentrationClinical investigationSubset of individualsGlycoprotein expressionCarcinomaImmunohistochemistryLandscape of somatic single-nucleotide and copy-number mutations in uterine serous carcinoma
Zhao S, Choi M, Overton JD, Bellone S, Roque DM, Cocco E, Guzzo F, English DP, Varughese J, Gasparrini S, Bortolomai I, Buza N, Hui P, Abu-Khalaf M, Ravaggi A, Bignotti E, Bandiera E, Romani C, Todeschini P, Tassi R, Zanotti L, Carrara L, Pecorelli S, Silasi DA, Ratner E, Azodi M, Schwartz PE, Rutherford TJ, Stiegler AL, Mane S, Boggon TJ, Schlessinger J, Lifton RP, Santin AD. Landscape of somatic single-nucleotide and copy-number mutations in uterine serous carcinoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 2916-2921. PMID: 23359684, PMCID: PMC3581983, DOI: 10.1073/pnas.1222577110.Peer-Reviewed Original ResearchConceptsNuRD chromatin-remodeling complexSomatic copy number variationsSomatic mutationsCell proliferation pathwaysCopy number mutationsDNA mismatch repairCopy number variationsCopy number lossChromatin remodelingTranscriptional machineryCopy number gainsChromosome segmentsFrequent mutationsChromosome 19Loss of TP53Cell cycleCancer genesWhole-exome sequencingBurden of mutationsMismatch repairProliferation pathwaysDNA damageMutational landscapeNormal DNAFrequent amplification
2011
Uterine and ovarian carcinosarcomas overexpressing Trop-2 are sensitive to hRS7, a humanized anti-Trop-2 antibody
Raji R, Guzzo F, Carrara L, Varughese J, Cocco E, Bellone S, Betti M, Todeschini P, Gasparrini S, Ratner E, Silasi DA, Azodi M, Schwartz P, Rutherford TJ, Buza N, Pecorelli S, Santin AD. Uterine and ovarian carcinosarcomas overexpressing Trop-2 are sensitive to hRS7, a humanized anti-Trop-2 antibody. Journal Of Experimental & Clinical Cancer Research 2011, 30: 106. PMID: 22075385, PMCID: PMC3224774, DOI: 10.1186/1756-9966-30-106.Peer-Reviewed Original ResearchConceptsAntibody-dependent cellular cytotoxicityAnti-Trop-2 antibodyTrop-2Cell linesEffective treatment optionChromium release assaysComplement-dependent cytotoxicityCarcinosarcoma cell lineCell surface markersOvarian carcinosarcomaTreatment optionsControl antibodyHRS7Cellular cytotoxicityHigher positivityTherapeutic strategiesHuman uterineTumor tissueFlow cytometryImmunohistochemistryRT-PCRSurface expressionAntibodiesHuman IgGCarcinosarcoma