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 properties
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 linesPIK3CA 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 responses
2011
Her2/neu extracellular domain shedding in uterine serous carcinoma: implications for immunotherapy with trastuzumab
Todeschini P, Cocco E, Bellone S, Varughese J, Lin K, Carrara L, Guzzo F, Buza N, Hui P, Silasi DA, Ratner E, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Her2/neu extracellular domain shedding in uterine serous carcinoma: implications for immunotherapy with trastuzumab. British Journal Of Cancer 2011, 105: 1176-1182. PMID: 21915118, PMCID: PMC3208497, DOI: 10.1038/bjc.2011.369.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsCulture Media, ConditionedFemaleFlow CytometryGenes, erbB-2HumansImmunohistochemistryImmunotherapyIn Situ Hybridization, FluorescenceMiddle AgedReal-Time Polymerase Chain ReactionTrastuzumabUterine NeoplasmsConceptsAntibody-dependent cell-mediated cytotoxicityTrastuzumab-mediated antibody-dependent cell-mediated cytotoxicityUSC cell linesHER2/neu expressionUSC patientsNeu expressionHER2/ECD levelsCell linesUterine serous carcinoma cell linesCell-mediated cytotoxicityUterine serous carcinomaChromium release assaysHER2/neuFISH-positive tumorsC-erbB2 gene amplificationTrastuzumab-induced cytotoxicityNeu tumorsHealthy womenSerous carcinomaCarcinoma cell linesReal-time PCRTherapeutic effectC-erbB2 genePatientsExpression of Tissue factor in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix: Implications for immunotherapy with hI-con1, a factor VII-IgGFcchimeric protein targeting tissue factor
Cocco E, Varughese J, Buza N, Bellone S, Glasgow M, Bellone M, Todeschini P, Carrara L, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Lockwood CJ, Santin AD. Expression of Tissue factor in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix: Implications for immunotherapy with hI-con1, a factor VII-IgGFcchimeric protein targeting tissue factor. BMC Cancer 2011, 11: 263. PMID: 21693061, PMCID: PMC3141777, DOI: 10.1186/1471-2407-11-263.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaCarcinoma, Squamous CellCell Line, TumorComplement System ProteinsCytotoxicity Tests, ImmunologicDrug Screening Assays, AntitumorFemaleHuman papillomavirus 16Human papillomavirus 18HumansImmunoconjugatesImmunoglobulin GImmunotherapyInterleukin-2KeratinocytesMolecular Targeted TherapyNeoplasm ProteinsNeovascularization, PathologicPapillomavirus InfectionsRNA, MessengerRNA, NeoplasmThromboplastinUterine Cervical NeoplasmsConceptsCervical cancer cell linesPrimary cervical cancer cell linesCervical carcinoma cell linesCancer cell linesCervical cancerCarcinoma cell linesFactor VII/VIIaTissue factorUterine cervixCell linesImportant worldwide health problemTargeting tissue factorStandard treatment modalitySquamous cell carcinomaExpression of TFWorldwide health problemNovel therapeutic agentsNormal cervical keratinocytesAdenocarcinoma histologyBackgroundCervical cancerCancer refractoryRecurrent diseaseCell carcinomaTreatment modalitiesNovel therapies
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
Overexpression of Epithelial Cell Adhesion Molecule in Primary, Metastatic, and Recurrent/Chemotherapy-Resistant Epithelial Ovarian Cancer: Implications for Epithelial Cell Adhesion Molecule-Specific Immunotherapy
Bellone S, Siegel ER, Cocco E, Cargnelutti M, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Overexpression of Epithelial Cell Adhesion Molecule in Primary, Metastatic, and Recurrent/Chemotherapy-Resistant Epithelial Ovarian Cancer: Implications for Epithelial Cell Adhesion Molecule-Specific Immunotherapy. International Journal Of Gynecological Cancer 2009, 19: 860-866. PMID: 19574774, DOI: 10.1111/igc.0b013e3181a8331f.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma, Clear CellAdenocarcinoma, MucinousAdultAntigens, NeoplasmAntineoplastic Combined Chemotherapy ProtocolsBlotting, WesternCarcinoma, PapillaryCell Adhesion MoleculesChemotherapy, AdjuvantCystadenocarcinoma, SerousDrug Resistance, NeoplasmEndometrial NeoplasmsEpithelial Cell Adhesion MoleculeFemaleFlow CytometryHumansImmunoenzyme TechniquesMiddle AgedNeoplasm Recurrence, LocalOrganoplatinum CompoundsOvarian NeoplasmsOvaryPrognosisRetrospective StudiesReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSurvival RateTreatment OutcomeTumor Cells, CulturedConceptsRecurrent epithelial ovarian carcinomaEpithelial ovarian carcinomaNormal ovarian tissuesOvarian carcinoma cell linesOvarian carcinomaEpithelial cell adhesion moleculeEp-CAMCarcinoma cell linesCell adhesion moleculeOvarian tissueChemotherapy-resistant epithelial ovarian cancerFlow cytometryCell linesAdhesion moleculesEp-CAM overexpressionStandard treatment modalityCell adhesion molecule expressionOvarian carcinoma patientsEpithelial ovarian cancerPrimary ovarian carcinomasAdhesion molecule expressionSurface expressionAntibody-mediated therapyHuman monoclonal antibodyEpithelial cell adhesion molecule (EpCAM) expression