2020
Preclinical Activity of Sacituzumab Govitecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2 (Trop-2) Linked to the Active Metabolite of Irinotecan (SN-38), in Ovarian Cancer
Perrone E, Lopez S, Zeybek B, Bellone S, Bonazzoli E, Pelligra S, Zammataro L, Manzano A, Manara P, Bianchi A, Buza N, Tymon-Rosario J, Altwerger G, Han C, Menderes G, Ratner E, Silasi DA, Azodi M, Hui P, Schwartz PE, Scambia G, Santin AD. Preclinical Activity of Sacituzumab Govitecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2 (Trop-2) Linked to the Active Metabolite of Irinotecan (SN-38), in Ovarian Cancer. Frontiers In Oncology 2020, 10: 118. PMID: 32117765, PMCID: PMC7028697, DOI: 10.3389/fonc.2020.00118.Peer-Reviewed Original ResearchTrop-2 expressionEOC cell linesSacituzumab govitecanEpithelial ovarian cancerPrimary tumor cell linesPreclinical activityTrop-2EOC xenograftsOvarian cancerTrophoblast cell surface antigen 2Cell linesActive metaboliteTumor cell linesImpressive anti-tumor activityCell surface antigen 2Lethal gynecologic malignancyHigh ADCC activityAnti-tumor activityParaffin-embedded tumorsSignificant bystander killingGynecologic malignanciesADCC activityEOC tissuesOvarian tumorsClinical trialsSacituzumab govitecan, an antibody‐drug conjugate targeting trophoblast cell‐surface antigen 2, shows cytotoxic activity against poorly differentiated endometrial adenocarcinomas in vitro and in vivo
Perrone E, Manara P, Lopez S, Bellone S, Bonazzoli E, Manzano A, Zammataro L, Bianchi A, Zeybek B, Buza N, Tymon‐Rosario J, Altwerger G, Han C, Menderes G, Huang GS, Ratner E, Silasi D, Azodi M, Hui P, Schwartz PE, Scambia G, Santin AD. Sacituzumab govitecan, an antibody‐drug conjugate targeting trophoblast cell‐surface antigen 2, shows cytotoxic activity against poorly differentiated endometrial adenocarcinomas in vitro and in vivo. Molecular Oncology 2020, 14: 645-656. PMID: 31891442, PMCID: PMC7053235, DOI: 10.1002/1878-0261.12627.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmAntineoplastic AgentsCamptothecinCarcinoma, EndometrioidCell Adhesion MoleculesCell DifferentiationCell Line, TumorCell SurvivalEndometrial NeoplasmsFemaleHumansImmunoconjugatesImmunohistochemistryIrinotecanMiceMice, SCIDTissue Array AnalysisXenograft Model Antitumor AssaysConceptsAntibody-dependent cell cytotoxicityCell surface antigen 2EC cell linesSacituzumab govitecanTrop-2 expressionPrimary tumor cell linesTrop-2Xenograft modelAntigen 2Cell linesTumor cell linesCommon gynecologic malignancyFuture clinical trialsChromium release assaysParaffin-embedded tumorsTumor growth inhibitionSignificant bystander killingEC xenograftsGynecologic malignanciesEndometrial cancerEndometrial adenocarcinomaEndometrioid carcinoma tissuesPreclinical activityControl antibodyClinical trials
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 abilityTumorsA novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma
Han C, Bellone S, Siegel ER, Altwerger G, Menderes G, Bonazzoli E, Egawa-Takata T, Pettinella F, Bianchi A, Riccio F, Zammataro L, Yadav G, Marto JA, Penet MF, Levine DA, Drapkin R, Patel A, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. A novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma. Gynecologic Oncology 2018, 149: 585-591. PMID: 29572027, PMCID: PMC5986604, DOI: 10.1016/j.ygyno.2018.03.050.Peer-Reviewed Original ResearchConceptsHigh-grade serous ovarian carcinomaSerous ovarian carcinomaIL-6Ovarian cancerOvarian carcinomaE-cadHigh-grade serous ovarian adenocarcinomaEarly-stage ovarian cancerROC analysisEarly detectionMajority of patientsLethal gynecologic malignancyStage ovarian cancerOvarian cancer patientsBenign gynecologic pathologyNon-cancer controlsSerous ovarian adenocarcinomaEffective cancer screeningSerous ovarian cancerMultiple biomarker panelsFour-marker panelHigh differential gene expressionGynecologic malignanciesCA 125IL-1ra
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 emtansineSYD985Superior in vitro and in vivo activity of trastuzumab-emtansine (T-DM1) in comparison to trastuzumab, pertuzumab and their combination in epithelial ovarian carcinoma with high HER2/neu expression
Menderes G, Bonazzoli E, Bellone S, Altwerger G, Black JD, Dugan K, Pettinella F, Masserdotti A, Riccio F, Bianchi A, Zammataro L, de Haydu C, Buza N, Hui P, Wong S, Huang GS, Litkouhi B, Ratner E, Silasi DA, Azodi M, Schwartz PE, Santin AD. Superior in vitro and in vivo activity of trastuzumab-emtansine (T-DM1) in comparison to trastuzumab, pertuzumab and their combination in epithelial ovarian carcinoma with high HER2/neu expression. Gynecologic Oncology 2017, 147: 145-152. PMID: 28705408, PMCID: PMC5605415, DOI: 10.1016/j.ygyno.2017.07.009.Peer-Reviewed Original ResearchConceptsHigh HER2/neu expressionHER2/neu expressionEpithelial ovarian cancerHER2/neuAnti-tumor activityEOC cell linesT-DM1Neu expressionChemotherapy-resistant epithelial ovarian cancerLimited anti-tumor activityAntibody-dependent cell-mediated cytotoxicity (ADCC) activityCell linesSuperior anti-tumor activityCombination of trastuzumabLethal gynecologic malignancyEpithelial ovarian carcinomaTumor growth inhibitionEOC xenograftsGynecologic malignanciesPreclinical dataOvarian carcinomaOvarian cancerClinical studiesXenograft modelSingle agentEfficacy of neratinib in the treatment of HER2/neu-amplified epithelial ovarian carcinoma in vitro and in vivo
Menderes G, Bonazzoli E, Bellone S, Black JD, Lopez S, Pettinella F, Masserdotti A, Zammataro L, Litkouhi B, Ratner E, Silasi DA, Azodi M, Schwartz PE, Santin AD. Efficacy of neratinib in the treatment of HER2/neu-amplified epithelial ovarian carcinoma in vitro and in vivo. Medical Oncology 2017, 34: 91. PMID: 28397106, PMCID: PMC5896014, DOI: 10.1007/s12032-017-0956-8.Peer-Reviewed Original ResearchConceptsEpithelial ovarian carcinomaOvarian carcinoma xenograftsOvarian cancerOvarian carcinomaCarcinoma xenograftsPreclinical efficacyCell linesTumor cell linesHER2/neu expressionChemotherapy-resistant diseaseOvarian cancer cell linesAvailable treatment strategiesEfficacy of neratinibInhibits xenograft growthNovel therapeutic agentsPrimary tumor cell linesG0/G1 phaseCell cycle distributionCell signaling changesNeratinib treatmentCancer cell linesGynecologic malignanciesOverall survivalNeu expressionClinical trials
2015
Neratinib shows efficacy in the treatment of HER2 amplified carcinosarcoma in vitro and in vivo
Schwab CL, English DP, Black J, Bellone S, Lopez S, Cocco E, Bonazzoli E, Bussi B, Predolini F, Ferrari F, Ratner E, Silasi DA, Azodi M, Rutherford T, Schwartz PE, Santin AD. Neratinib shows efficacy in the treatment of HER2 amplified carcinosarcoma in vitro and in vivo. Gynecologic Oncology 2015, 139: 112-117. PMID: 26260909, PMCID: PMC4587290, DOI: 10.1016/j.ygyno.2015.08.002.Peer-Reviewed Original ResearchConceptsHER2/neuTreatment of HER2Efficacy of neratinibCarcinosarcoma cell lineTumor growthCell linesEffective treatment optionDeadliest gynecologic malignancyG0/G1 phaseCell cycle distributionCell signaling changesActivation of S6Neratinib treatmentGynecologic malignanciesOverall survivalTreatment optionsClinical trialsXenograft growthNew therapiesHER2NeratinibFlow cytometryNeuCycle distributionSignaling changes
2014
Institutional Review of Primary Non-Hodgkin Lymphoma of the Female Genital Tract
Ahmad AK, Hui P, Litkouhi B, Azodi M, Rutherford T, McCarthy S, Xu ML, Schwartz PE, Ratner E. Institutional Review of Primary Non-Hodgkin Lymphoma of the Female Genital Tract. International Journal Of Gynecological Cancer 2014, 24: 1250-1255. PMID: 25010039, PMCID: PMC8139417, DOI: 10.1097/igc.0000000000000201.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBleomycinCombined Modality TherapyCyclophosphamideCytarabineDiagnosis, DifferentialDoxorubicinFemaleGenital Neoplasms, FemaleGynecologic Surgical ProceduresHumansLymphoma, Non-HodgkinMiddle AgedPrednisolonePrednisonePregnancyPregnancy Complications, NeoplasticRetrospective StudiesSurvival AnalysisTeniposideVincristineYoung AdultConceptsNon-Hodgkin lymphomaFemale genital tractGenital tractGynecologic malignanciesPara-aortic lymph nodesPrimary non-Hodgkin lymphomaDiffuse large B-cell lymphomaYale-New Haven HospitalLarge B-cell lymphomaConcomitant radiation therapyRadical gynecologic surgeryCommon histologic typeOverall median survivalSingle institution experienceStem cell transplantationRare gynecologic malignancyDiagnosis of lymphomaAnn Arbor systemB-cell lymphomaWorld Health OrganizationMedian survivalRecurrent diseaseCombination chemotherapyMedian ageUterine corpus
2013
Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment
Craveiro V, Yang-Hartwich Y, Holmberg JC, Joo WD, Sumi NJ, Pizzonia J, Griffin B, Gill SK, Silasi DA, Azodi M, Rutherford T, Alvero AB, Mor G. Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment. Cancer Medicine 2013, 2: 751-762. PMID: 24403249, PMCID: PMC3892380, DOI: 10.1002/cam4.115.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, PhytogenicCarcinoma, Ovarian EpithelialDrug Resistance, NeoplasmFemaleHEK293 CellsHumansHyaluronan ReceptorsMiceMice, NudeMyeloid Differentiation Factor 88Neoplasms, Glandular and EpithelialNeoplastic Stem CellsOvarian NeoplasmsPaclitaxelPhenotypeRecurrenceSnail Family Transcription FactorsTranscription FactorsTumor BurdenXenograft Model Antitumor AssaysConceptsEpithelial ovarian cancerRecurrent epithelial ovarian cancerOvarian cancer stem cellsEOC stem cellsCancer stem cellsQuantitative polymerase chain reactionRecurrent diseaseOvarian cancerEOC cellsVivo ovarian cancer modelsStem cellsDoses of paclitaxelLethal gynecologic malignancyOvarian cancer modelProcess of recurrenceWestern blot analysisMaintenance therapyGynecologic malignanciesPrimary diseaseAggressive diseaseEOC patientsPrimary tumorPolymerase chain reactionAggressive phenotypePaclitaxel treatment
2006
0692: The Incidence of Postoperative Delirium in Geriatric Patients Undergoing Surgery for Suspected Gynecologic Malignancies
Mcalpine J, Hodgson E, Richman S, Zelterman D, Su Y, Abramovitz S, Kelly M, Azodi M, Rutherford T, Schwartz P. 0692: The Incidence of Postoperative Delirium in Geriatric Patients Undergoing Surgery for Suspected Gynecologic Malignancies. International Journal Of Gynecological Cancer 2006, 16: 794.2-794. DOI: 10.1136/ijgc-00009577-200610001-00692.Peer-Reviewed Original ResearchAtypical presentations of carboplatin hypersensitivity reactions: Characterization and management in patients with gynecologic malignancies
McAlpine JN, Kelly MG, O'Malley DM, Azodi M, Coombe K, Schwartz PE, Rutherford TJ. Atypical presentations of carboplatin hypersensitivity reactions: Characterization and management in patients with gynecologic malignancies. Gynecologic Oncology 2006, 103: 288-292. PMID: 16647749, DOI: 10.1016/j.ygyno.2006.03.007.Peer-Reviewed Original ResearchConceptsSkin testingPlatinum hypersensitivityAllergy symptomsCarboplatin cycleLife-threatening adverse eventsCarboplatin skin testingCarboplatin-treated patientsCycles/patientDuration of symptomsRetrospective chart reviewSystemic allergic reactionsCarboplatin hypersensitivity reactionsContinuation of treatmentNegative predictive valueAPH patientsChart reviewChemotherapeutic cyclesGynecologic malignanciesAdverse eventsAtypical presentationDose escalationMedian onsetHypersensitivity reactionsAllergic reactionsMedian number