2022
Synergistic 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
DHES0815A, 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 variantsHyperimmune plasma infusion in an immunocompromised Covid-19 patient previously treated for follicular lymphoma
Levi G, Rocchetti C, Magri R, Uccelli S, Bottone D, Quadri F, Novali M, Santin AD, Bezzi M. Hyperimmune plasma infusion in an immunocompromised Covid-19 patient previously treated for follicular lymphoma. Monaldi Archives For Chest Disease 2021, 91 PMID: 34121379, DOI: 10.4081/monaldi.2021.1867.Peer-Reviewed Original ResearchConceptsPlasma infusionFollicular lymphomaHyperimmune plasmaCOVID-19COVID-19 patientsStandard of careInflammatory indexFirst doseImmunocompetent patientsRadiological findingsSecond doseNasopharyngeal swabsPoor prognosisCaucasian womenImproved outcomesPositive testPatientsSubsequent onsetLimited dataFeverLymphomaInfusionDoseDaysObinutuzumab
2020
Uterine serous carcinoma: Molecular features, clinical management, and new and future therapies
Lee EK, Fader AN, Santin AD, Liu JF. Uterine serous carcinoma: Molecular features, clinical management, and new and future therapies. Gynecologic Oncology 2020, 160: 322-332. PMID: 33160694, DOI: 10.1016/j.ygyno.2020.10.017.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaMolecular featuresDistant recurrenceExtrauterine spreadMultimodality treatmentEndometrial cancerPoor prognosisSerous carcinomaAggressive subtypeClinical managementNovel therapiesFuture therapiesCurrent managementTherapyKey molecular featuresChemotherapySurgeryCarcinomaPrognosisRecurrenceRadiotherapyCancerSubtypesPreclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas
Lopez S, Perrone E, Bellone S, Bonazzoli E, Zeybek B, Han C, Tymon-Rosario J, Altwerger G, Menderes G, Bianchi A, Zammataro L, Manzano A, Manara P, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Raspagliesi F, Angioli R, Buza N, Hui P, Bond HM, Santin AD. Preclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas. Oncotarget 2020, 11: 560-570. PMID: 32082489, PMCID: PMC7007291, DOI: 10.18632/oncotarget.27342.Peer-Reviewed Original ResearchSacituzumab govitecanTrop-2 expressionTrop-2Ovarian carcinosarcomaWeekly intravenous administrationSignificant tumor growth inhibitionTumor growth inhibitionCS cell linesCell linesCell surface markersNegative cell linesAggressive carcinosarcomasCarcinosarcoma patientsPrimary carcinosarcomaOverall survivalPoor prognosisPreclinical activityRare cancersIntravenous administrationXenograft modelActive drugCarcinosarcomaActive metaboliteFFPE tumorsCell viability assays
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
Novel targeted therapies in ovarian and uterine carcinosarcomas.
Han C, Altwerger G, Menderes G, Haines K, Feinberg J, Lopez S, Manzano A, Varughese J, Santin AD. Novel targeted therapies in ovarian and uterine carcinosarcomas. Discovery Medicine 2018, 25: 309-319. PMID: 30021104.Peer-Reviewed Original ResearchConceptsMultiple genes/pathwaysPI3K/Akt/mTORFemale genital tractEffective treatment strategiesUnmet medical needAkt/mTORGynecologic tumorsPoor prognosisUterine carcinosarcomaAggressive tumorsTreatment modalitiesBiphasic tumorWhole-exome sequencing studiesGenital tractTreatment strategiesCarcinomatous componentCarcinosarcomaMedical needAberrant activationTumorsGenes/pathwaysCell cycle regulationGenetic landscapeSequencing studiesPrognosis
2015
Solitomab, 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 lymphocytes
2014
T-DM1, a novel antibody-drug conjugate, is highly effective against uterine and ovarian carcinosarcomas overexpressing HER2
Nicoletti R, Lopez S, Bellone S, Cocco E, Schwab CL, Black JD, Centritto F, Zhu L, Bonazzoli E, Buza N, Hui P, Mezzanzanica D, Canevari S, Schwartz PE, Rutherford TJ, Santin AD. T-DM1, a novel antibody-drug conjugate, is highly effective against uterine and ovarian carcinosarcomas overexpressing HER2. Clinical & Experimental Metastasis 2014, 32: 29-38. PMID: 25398397, PMCID: PMC4310789, DOI: 10.1007/s10585-014-9688-8.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsCarcinosarcomaCell Line, TumorCell ProliferationFemaleImmunoconjugatesM Phase Cell Cycle CheckpointsMaytansineMiceMice, SCIDOvarian NeoplasmsReceptor, ErbB-2TrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsCS cell linesT-DM1Cell linesFlow cytometryNovel antibody-drug conjugateAggressive clinical behaviorNovel treatment optionsG2/M phase cell cycle arrestHER2 protein overexpressionM phase cell cycle arrestPhase cell cycle arrestAntibody-drug conjugatesDisease refractoryPrimary HER2Vehicle miceOvarian carcinosarcomaPoor prognosisUterine carcinosarcomaCS patientsTreatment optionsClinical behaviorLonger survivalCell cycle arrestHER2 amplificationCarcinosarcomaRegulation of tumor cell migration and invasion by the H19/let-7 axis is antagonized by metformin-induced DNA methylation
Yan L, Zhou J, Gao Y, Ghazal S, Lu L, Bellone S, Yang Y, Liu N, Zhao X, Santin AD, Taylor H, Huang Y. Regulation of tumor cell migration and invasion by the H19/let-7 axis is antagonized by metformin-induced DNA methylation. Oncogene 2014, 34: 3076-3084. PMID: 25088204, DOI: 10.1038/onc.2014.236.Peer-Reviewed Original ResearchConceptsTumor cell migrationDNA methylationCell migrationTumor suppressorH19/letPotent tumor suppressorExpression of oncogenesDiverse human cancersMetastasis-promoting genesAnti-diabetic drug metforminLet-7C-MycHuman cancersH19Cell growthNovel mechanismEndometrial cancerPoor prognosisRegulationDrug metforminMethylationTherapeutic opportunitiesSuppressorTumor cellsOncogene
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 expressionCarcinomaImmunohistochemistryClass III β-tubulin overexpression in ovarian clear cell and serous carcinoma as a maker for poor overall survival after platinum/taxane chemotherapy and sensitivity to patupilone
Roque DM, Bellone S, Buza N, Romani C, Cocco E, Bignotti E, Ravaggi A, Rutherford TJ, Schwartz PE, Pecorelli S, Santin AD. Class III β-tubulin overexpression in ovarian clear cell and serous carcinoma as a maker for poor overall survival after platinum/taxane chemotherapy and sensitivity to patupilone. American Journal Of Obstetrics And Gynecology 2013, 209: 62.e1-62.e9. PMID: 23583215, DOI: 10.1016/j.ajog.2013.04.017.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily B, Member 1Cell LineCystadenocarcinoma, SerousDose-Response Relationship, DrugDown-RegulationDrug Resistance, NeoplasmEpothilonesFemaleHumansImmunohistochemistryKaplan-Meier EstimateMicrotubulesNeoplasms, Glandular and EpithelialOvarian NeoplasmsPaclitaxelPrognosisReal-Time Polymerase Chain ReactionTaxoidsTubulinTubulin ModulatorsConceptsClass III β-tubulinClear cell carcinomaIII β-tubulinCell carcinomaOverall survivalP-glycoproteinClass III β-tubulin overexpressionClinical outcomesPolymerase chain reactionPaclitaxel resistanceClass III β-tubulin expressionPlatinum/taxane chemotherapyPoor overall survivalSerous papillary carcinomaChain reactionOvarian clear cellFresh frozen tissue samplesReal-time polymerase chain reactionCell linesTime polymerase chain reactionPolymerase chain reaction resultsΒ-tubulin expressionTaxane chemotherapyPoor outcomePoor prognosis
2012
Targeted therapy for high-risk endometrial carcinoma
Roque D, Schwartz P, Santin A. Targeted therapy for high-risk endometrial carcinoma. Journal Of Clinical Practice 2012, 9: 539-554. DOI: 10.2217/cpr.12.44.Peer-Reviewed Original ResearchType II endometrial cancerEndometrial cancerHigh-risk endometrial carcinomaHigh-risk cancerAggressive clinical courseRational therapeutic strategiesMolecular pathway alterationsClinical courseEndometrial carcinomaPoor prognosisClinical behaviorDisease burdenTargeted therapyTherapeutic strategiesSmall molecule inhibitorsClinical advancesPathway alterationsDistinct histopathologyCytotoxic agentsCancerCurrent standardImmunotherapyMolecular characterizationCarcinomaPrognosis
2011
The significance of perineural invasion in early-stage cervical cancer
ElSahwi KS, Barber E, Illuzzi J, Buza N, Ratner E, Silasi DA, Santin AD, Azodi M, Schwartz PE, Rutherford TJ. The significance of perineural invasion in early-stage cervical cancer. Gynecologic Oncology 2011, 123: 561-564. PMID: 21968340, DOI: 10.1016/j.ygyno.2011.08.028.Peer-Reviewed Original ResearchConceptsEarly cervical cancerPerineural invasionCervical cancerRisk factorsAdjuvant therapyEarly-stage cervical cancer patientsEarly-stage cervical cancerMultiple high-risk factorsAdjusted hazard ratioIndependent risk factorRetrospective chart reviewLymphovascular space invasionCervical cancer patientsLarger tumor sizeHigh-risk factorsChart reviewHazard ratioCervical stromaParametrial invasionWorse prognosisPoor prognosisSpace invasionTumor sizeMean ageTumor extension
2005
Amplification of c‐erbB2 oncogene
Santin AD, Bellone S, Van Stedum S, Bushen W, Palmieri M, Siegel ER, De Las Casas LE, Roman JJ, Burnett A, Pecorelli S. Amplification of c‐erbB2 oncogene. Cancer 2005, 104: 1391-1397. PMID: 16116605, DOI: 10.1002/cncr.21308.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAgedBiomarkers, TumorBiopsy, NeedleCystadenocarcinoma, PapillaryFemaleGene AmplificationGene Expression Regulation, NeoplasticGenes, erbB-2HumansImmunohistochemistryIn Situ Hybridization, FluorescenceMiddle AgedProbabilityPrognosisReceptor, ErbB-2Risk AssessmentSampling StudiesSensitivity and SpecificityStatistics, NonparametricSurvival AnalysisUterine NeoplasmsConceptsNeu gene amplificationHER-2/neu geneEndometrial carcinomaGene amplificationSerous papillary endometrial carcinomaTumor cellsHER-2/neuNeu genePapillary endometrial carcinomaKaplan-Meier curvesImportant prognostic indicatorAfrican American patientsDisease-related deathLog-rank testShorter survival timeFISH-negative patientsNovel treatment strategiesC patientsSame tumor samplesAggressive variantPatient survivalPoor outcomePoor prognosisPrognostic indicatorClinical management