2023
In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma.
Mutlu L, Manavella D, Bellone S, McNamara B, Harold J, Mauricio D, Siegel E, Buza N, Hui P, Hartwich T, Yang-Hartwich Y, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Dottino P, Schwartz P, Santin A. In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma. Molecular Cancer Therapeutics 2023, 22: 1404-1412. PMID: 37676984, DOI: 10.1158/1535-7163.mct-23-0126.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaAntibody-dependent cellular cytotoxicityT-DXdUSC patientsUSC cell linesTrastuzumab deruxtecanSerous carcinomaHER2 expressionClinical trialsRecurrent uterine serous carcinomaTopoisomerase I inhibitor payloadSignificant antibody-dependent cellular cytotoxicityCell linesMultiple tumor indicationsPrimary USC cell linesLow HER2 expressionFuture clinical trialsHigh recurrence ratePeripheral blood lymphocytesERBB2 gene amplificationGrowth suppressionHER2-overexpressing cell linesTumor growth suppressionOverall survivalStandard chemotherapy
2018
MicroRNA 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
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
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 agent
2016
Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro
Bellone S, Bignotti E, Lonardi S, Ferrari F, Centritto F, Masserdotti A, Pettinella F, Black J, Menderes G, Altwerger G, Hui P, Lopez S, de Haydu C, Bonazzoli E, Predolini F, Zammataro L, Cocco E, Ferrari F, Ravaggi A, Romani C, Facchetti F, Sartori E, Odicino FE, Silasi DA, Litkouhi B, Ratner E, Azodi M, Schwartz PE, Santin AD. Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro. Gynecologic Oncology 2016, 144: 146-152. PMID: 27894751, PMCID: PMC5183545, DOI: 10.1016/j.ygyno.2016.11.023.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsCarboplatinCarcinomaCD4 Lymphocyte CountCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell SurvivalDisease-Free SurvivalDNA Polymerase IIDrug Resistance, NeoplasmEndometrial NeoplasmsFemaleHumansMicrosatellite InstabilityMiddle AgedMutationPoly-ADP-Ribose Binding ProteinsTumor Cells, CulturedConceptsBetter prognosisTumor cell linesInfiltration of CD4Number of CD4Platinum-based chemotherapyT lymphocyte infiltrationPD-1 receptorCell linesLow metastatic capabilityPOLE-mutated tumorsWild-type ECsEC cell linesLymphocyte infiltrationFavorable prognosisPD-1EC patientsType tumorsEnhanced immunogenicityT lymphocytesMolecular subtypesTumors correlatesChemotherapyMetastatic capabilityPrognosisTumors
2014
Taselisib, a selective inhibitor of PIK3CA, is highly effective on PIK3CA-mutated and HER2/neu amplified uterine serous carcinoma in vitro and in vivo
Lopez S, Schwab CL, Cocco E, Bellone S, Bonazzoli E, English DP, Schwartz PE, Rutherford T, Angioli R, Santin AD. Taselisib, a selective inhibitor of PIK3CA, is highly effective on PIK3CA-mutated and HER2/neu amplified uterine serous carcinoma in vitro and in vivo. Gynecologic Oncology 2014, 135: 312-317. PMID: 25172762, PMCID: PMC4270135, DOI: 10.1016/j.ygyno.2014.08.024.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntineoplastic AgentsCarcinomaCell Cycle CheckpointsCell Line, TumorCell ProliferationClass I Phosphatidylinositol 3-KinasesDrug Screening Assays, AntitumorFemaleGene AmplificationHumansImidazolesIn Situ Hybridization, FluorescenceIn Vitro TechniquesMiceMiddle AgedNeoplasms, Cystic, Mucinous, and SerousOxazepinesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsReceptor, ErbB-2Uterine NeoplasmsXenograft Model Antitumor AssaysConceptsHER2/neu gene amplificationUterine serous carcinomaUSC cell linesNeu gene amplificationCell linesHER2/neuPIK3CA mutationsGene amplificationPhosphorylation of S6Serous carcinomaPIK3CA wild typeG0/G1 phaseSelective inhibitorOncogenic PIK3CA mutationsS6 proteinCell cycle distributionPrimary uterine serous carcinomaWild typeDownstream signalingPrimary USC cell linesCell cycleNovel therapeutic optionsDose-dependent increaseDifferential growth inhibitionG1 phaseT‐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
2010
Primary Cervical Carcinoma Cell Lines Overexpress Epithelial Cell Adhesion Molecule (EpCAM) and Are Highly Sensitive to Immunotherapy With MT201, a Fully Human Monoclonal Anti-EpCAM Antibody
Richter CE, Cocco E, Bellone S, Bellone M, Casagrande F, Todeschini P, Rüttinger D, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Primary Cervical Carcinoma Cell Lines Overexpress Epithelial Cell Adhesion Molecule (EpCAM) and Are Highly Sensitive to Immunotherapy With MT201, a Fully Human Monoclonal Anti-EpCAM Antibody. International Journal Of Gynecological Cancer 2010, 20: 1440-1447. PMID: 21370592, PMCID: PMC3701951, DOI: 10.1111/igc.0b013e3181fb18a1.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntigens, NeoplasmCarcinomaCell Adhesion MoleculesCell Culture TechniquesCell Line, TumorEpithelial Cell Adhesion MoleculeFemaleFlow CytometryGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunotherapyMiddle AgedTreatment OutcomeUterine Cervical NeoplasmsYoung AdultConceptsCervical carcinoma cell linesEpithelial cell adhesion moleculeComplement-dependent cytotoxicityCervical cancer cell linesInterleukin-2Real-time polymerase chain reactionCarcinoma cell linesCell adhesion moleculeCancer cell linesAggressive tumorsPolymerase chain reactionAdhesion moleculesPrimary cervical cancer cell linesCell linesRelease assaysFlow cytometryHighest messenger RNA expressionStandard salvage therapyCell adhesion molecule expressionEffective treatment optionAdhesion molecule expressionChain reactionHuman monoclonal antibodyMessenger RNA expressionEpithelial cell adhesion molecule (EpCAM) expression
2009
Human Kallikrein 5
Bandiera E, Zanotti L, Bignotti E, Romani C, Tassi R, Todeschini P, Tognon G, Ragnoli M, Santin AD, Gion M, Pecorelli S, Ravaggi A. Human Kallikrein 5. International Journal Of Gynecological Cancer 2009, 19: 1015-1021. PMID: 19820362, DOI: 10.1111/igc.0b013e3181ab597f.Peer-Reviewed Original ResearchConceptsOvarian carcinomaBorderline tumorsHealthy controlsPathological lesionsKLK5 levelsSpontaneous humoral immune responseBenign pathological lesionsImmune-based therapiesOvarian borderline tumorsSera of patientsHumoral immune responseBenign pelvic massesOvarian cancer progressionPotential new biomarkersEnzyme-linked immunosorbentOvarian cancer detectionHealthy womenPelvic massHumoral responseAntibody responseObstetricians stageImmune responsePatientsNew biomarkersCarcinoma
2007
Human Papillomavirus Type 16 and 18 E7-Pulsed Dendritic Cell Vaccination of Stage IB or IIA Cervical Cancer Patients: a Phase I Escalating-Dose Trial
Santin AD, Bellone S, Palmieri M, Zanolini A, Ravaggi A, Siegel ER, Roman JJ, Pecorelli S, Cannon MJ. Human Papillomavirus Type 16 and 18 E7-Pulsed Dendritic Cell Vaccination of Stage IB or IIA Cervical Cancer Patients: a Phase I Escalating-Dose Trial. Journal Of Virology 2007, 82: 1968-1979. PMID: 18057249, PMCID: PMC2258728, DOI: 10.1128/jvi.02343-07.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, ViralAntibody FormationCancer VaccinesCarcinomaCD4-Positive T-LymphocytesDendritic CellsDNA-Binding ProteinsEnzyme-Linked Immunosorbent AssayFemaleHemocyaninsHumansImmunity, CellularNeoplasm StagingOncogene Proteins, ViralPapillomavirus E7 ProteinsPapillomavirus VaccinesRecombinant ProteinsUterine Cervical NeoplasmsVaccinationConceptsCervical cancer patientsIIA cervical cancer patientsDendritic cell vaccinationHuman papillomavirus type 16Cancer patientsDC vaccinationStage IBPapillomavirus type 16Cell vaccinationE7 antigenType 16Delayed-type hypersensitivity reactionEnzyme-linked immunosorbent spotHPV E7 antigenLimited tumor burdenT-cell countsEvidence of diseaseIIA cervical cancerT cell responsesKeyhole limpet hemocyaninEnzyme-linked immunosorbentHPV16/18 E7Vaccine doseAutologous DCsDTH responseClaudin 4 identifies a wide spectrum of epithelial neoplasms and represents a very useful marker for carcinoma versus mesothelioma diagnosis in pleural and peritoneal biopsies and effusions
Facchetti F, Lonardi S, Gentili F, Bercich L, Falchetti M, Tardanico R, Baronchelli C, Lucini L, Santin A, Murer B. Claudin 4 identifies a wide spectrum of epithelial neoplasms and represents a very useful marker for carcinoma versus mesothelioma diagnosis in pleural and peritoneal biopsies and effusions. Virchows Archiv 2007, 451: 669-680. PMID: 17609977, DOI: 10.1007/s00428-007-0448-x.Peer-Reviewed Original ResearchConceptsDiagnosis of mesotheliomaSpindle cell neoplasmCell neoplasmsEpithelial neoplasmsFollicular dendritic cell sarcomaDendritic cell sarcomaBiphasic synovial sarcomaNeoplastic mesothelial cellsMetastatic tumor cellsSerosal metastasisPeritoneal biopsiesReactive effusionsMetastatic carcinomaSynovial sarcomaPrimary carcinomaCell sarcomaMesotheliomaMesothelial cellsMesothelioma diagnosisReactive mesotheliumUseful markerCarcinomaClaudin-4NeoplasmsCytological samples
2006
Correlation between serological immune response analyzed by a new ELISA for HPV-16/18 E7 oncoprotein and clinical characteristics of cervical cancer patients
Ravaggi A, Romani C, Pasinetti B, Tassi RA, Bignotti E, Bandiera E, Odicino FE, Ragnoli M, Donzelli C, Falchetti M, Calza S, Santin AD, Pecorelli S. Correlation between serological immune response analyzed by a new ELISA for HPV-16/18 E7 oncoprotein and clinical characteristics of cervical cancer patients. Archives Of Virology 2006, 151: 1899-1916. PMID: 16732494, DOI: 10.1007/s00705-006-0787-y.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, ViralAntibody SpecificityBiomarkersBiotinCancer VaccinesCarcinomaDisease ProgressionDNA-Binding ProteinsEnzyme-Linked Immunosorbent AssayFemaleHumansImmunoglobulin GOncogene Proteins, ViralPapillomavirus E7 ProteinsPapillomavirus VaccinesPrecancerous ConditionsRecombinant ProteinsSensitivity and SpecificityStreptavidinUterine Cervical NeoplasmsVaccinationConceptsCervical cancer patientsCancer patientsHealthy womenHuman papillomavirusE7 oncoproteinsPre-invasive neoplasiaAutologous dendritic cellsSerological immune responsesCervical cancer developmentCapture ELISA methodType of responseHPV 16/18Clinical characteristicsDendritic cellsAntibody levelsAntibody inductionCervical carcinomaSerological evaluationAntibody prevalenceImmune responseAdjunctive toolPatientsCancer developmentELISA methodPotential marker
1996
Effects of Irradiation on the Expression of Surface Antigens in Human Ovarian Cancer
Santin A, Hiserodt J, Fruehauf J, DiSaia P, Pecorelli S, Granger G. Effects of Irradiation on the Expression of Surface Antigens in Human Ovarian Cancer. Gynecologic Oncology 1996, 60: 468-474. PMID: 8774659, DOI: 10.1006/gyno.1996.0075.Peer-Reviewed Original ResearchConceptsMHC class ISurface antigenHER2-neuHigh dosesClass IITumor cellsCell linesClass IICAM-1 antigenHuman ovarian cancerHuman ovarian carcinoma cell linesOvarian carcinoma cell linesCA 125Carcinoma cell linesOvarian cancerICAM-1Radiation therapyIrradiation-induced upregulationImmune recognitionTumor tissueAntigenDosesCellsExposureExpression