2024
Targetable ERBB2/HER2 Mutations in Gynecologic Malignancies: Clinicopathological, Immunohistochemical, and Molecular Correlations.
Manrai P, McHenry A, Sun T, Santin A, Ratner E, Lin D, Elvin J, Hui P, Buza N. Targetable ERBB2/HER2 Mutations in Gynecologic Malignancies: Clinicopathological, Immunohistochemical, and Molecular Correlations. International Journal Of Gynecological Pathology 2024 PMID: 38914011, DOI: 10.1097/pgp.0000000000001050.Peer-Reviewed Original ResearchEndometrial carcinomaGynecologic malignanciesTyrosine kinase domainHER2-mutated non-small cell lung cancerTargeted anti-HER2 therapyNon-small cell lung cancerHigh-grade endometrioid adenocarcinomasFam-trastuzumab deruxtecanOvarian mucinous adenocarcinomaAnti-HER2 therapyAnti-HER2 drugsHER2 3+US Food and Drug AdministrationCell lung cancerEndometrial serous carcinomaSolid tumor typesStandard treatment recommendationsFood and Drug AdministrationFluorescence in situ hybridizationGynecological cancer typesEndometrial primaryMullerian originSerous carcinomaHER2 IHCEndometrioid adenocarcinoma
2023
Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression
Mauricio D, Bellone S, Mutlu L, McNamara B, Manavella D, Demirkiran C, Verzosa M, Buza N, Hui P, Hartwich T, Harold J, Yang-Hartwich Y, Zipponi M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Santin A. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression. Gynecologic Oncology 2023, 170: 38-45. PMID: 36610380, PMCID: PMC10445234, DOI: 10.1016/j.ygyno.2022.12.018.Peer-Reviewed Original ResearchConceptsHER2/neu expressionDS-8201aAntibody-drug conjugatesNeu expressionCS cell linesTrastuzumab deruxtecanOvarian carcinosarcomaTopoisomerase I inhibitor payloadCell linesAggressive gynecologic malignancyLimited therapeutic optionsEffective antibody-drug conjugatesCarcinosarcoma cell lineGynecologic malignanciesTherapeutic optionsIsotype controlSarcomatous elementsXenograft modelBystander killingFlow cytometryTumor cellsCarcinosarcomaAntitumor activityVivo studiesVivo activity
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 abilityTumors
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 agentComprehensive Analysis of PAX8 Expression in Epithelial Malignancies of the Uterine Cervix
Wong S, Hong W, Hui P, Buza N. Comprehensive Analysis of PAX8 Expression in Epithelial Malignancies of the Uterine Cervix. International Journal Of Gynecological Pathology 2017, 36: 101-106. PMID: 27362905, DOI: 10.1097/pgp.0000000000000309.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaEpithelial malignanciesPAX8 expressionAdenosquamous carcinomaMajority of SCCsCervical squamous cell carcinomaPossible primary sitesEndometrioid-type tumorsWeak nuclear stainingTissue microarray slidesGynecologic malignanciesEndometrial adenocarcinomaEndometrioid adenocarcinomaMetastatic lesionsEndometrial carcinomaMetastatic sitesUterine cervixCell carcinomaCervical tumorsEndocervical adenocarcinomaDifferential diagnosisPrimary siteAdenocarcinomaCarcinomaMalignancy
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
2011
Urinary hCG Screening in the Gynecologic Oncology Population
Richter C, Buza N, Hui P, Silasi D, Azodi M, Santin A, Rutherford T, Schwartz P. Urinary hCG Screening in the Gynecologic Oncology Population. Journal Of Gynecologic Surgery 2011, 27: 143-146. DOI: 10.1089/gyn.2010.0048.Peer-Reviewed Original ResearchGestational trophoblastic diseasePositive urine pregnancy testUrine pregnancy testGynecologic malignanciesUrinary hCGTrophoblastic diseasePregnancy testHuman chorionic gonadotropin testingClear cell ovarian carcinomaGynecologic oncology clinicGynecologic oncology populationRetrospective chart reviewHCG testingChart reviewNonpregnant patientsConsecutive patientsOncology populationPrimary peritonealOncology clinicVaginal carcinomaNongynecologic malignanciesUterine cancerFallopian tubeOvarian carcinomaOvarian cancer