2023
The Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo
Han C, McNamara B, Bellone S, Harold J, Manara P, Hartwich T, Mutlu L, Yang-Hartwich Y, Zipponi M, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Dottino P, Schwartz P, Santin A. The Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo. Gynecologic Oncology 2023, 170: 172-178. PMID: 36706643, PMCID: PMC10023457, DOI: 10.1016/j.ygyno.2023.01.015.Peer-Reviewed Original ResearchConceptsCombination of olaparibOvarian cancerHER2 expressionSingle agentCell linesGynecologic cancer mortalityHER2-negative tumorsOvarian cancer cell linesOvarian cancer patientsEpithelial ovarian carcinomaNovel therapeutic optionsOC cell linesUnmet medical needPoly (ADP-ribose) polymerase (PARP) inhibitorsPan-ErbB inhibitorSingle-agent olaparibPolymerase inhibitor olaparibPoly (ADP-ribose) polymerase (PARP) inhibitor olaparibPrimary HER2Cancer cell linesNegative tumorsTherapeutic optionsCancer mortalityCancer patientsNeu expressionTrastuzumab 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
2016
Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer
Yin M, Li X, Tan S, Zhou HJ, Ji W, Bellone S, Xu X, Zhang H, Santin AD, Lou G, Min W. Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer. Journal Of Clinical Investigation 2016, 126: 4157-4173. PMID: 27721235, PMCID: PMC5096908, DOI: 10.1172/jci87252.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsErbB ReceptorsFemaleHeterograftsHumansIntercellular Adhesion Molecule-1Macrophage-1 AntigenMacrophagesMiceMice, NudeNeoplasm MetastasisNeoplasm ProteinsNeoplasm TransplantationOvarian NeoplasmsSpheroids, CellularVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1ConceptsTumor-associated macrophagesOvarian cancerTranscoelomic metastasisTumor cellsICAM-1Mouse modelEpithelial ovarian cancerOvarian cancer growthOvarian cancer metastasisSpheroid formationOvarian cancer progressionVEGF/VEGFRTumor cell proliferationPharmacological blockadeMetastatic cancerColon cancerCancer growthMetastasisAntibody neutralizationTumor growthCancerClinical pathologyCancer metastasisCancer progressionΑMβ2 integrin
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
2008
Induction of human tumor‐associated differentially expressed gene‐12 (TADG‐12/TMPRSS3)‐specific cytotoxic T lymphocytes in human lymphocyte antigen‐A2.1–positive healthy donors and patients with advanced ovarian cancer
Bellone S, Anfossi S, O'Brien TJ, Cannon MJ, Silasi D, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Induction of human tumor‐associated differentially expressed gene‐12 (TADG‐12/TMPRSS3)‐specific cytotoxic T lymphocytes in human lymphocyte antigen‐A2.1–positive healthy donors and patients with advanced ovarian cancer. Cancer 2008, 115: 800-811. PMID: 19117353, DOI: 10.1002/cncr.24048.Peer-Reviewed Original ResearchConceptsOvarian cancer patientsPeptide-specific CTLsOvarian cancerCancer patientsHealthy donorsLymphocyte antigenEnzyme-linked immunosorbent spot-forming cell assayHuman cytotoxic T-lymphocyte responsesNatural killer-sensitive K562 cellsAnti-HLA class I monoclonal antibodiesImmunogenic peptidesPeptide-loaded target cellsType 1 cytokine profileAdvanced stage ovarian cancerCytotoxic T lymphocyte responsesSpecific cytotoxic T lymphocytesClass I monoclonal antibodiesMonoclonal antibody stimulationPotential immunogenic peptidesDendritic cell immunotherapyAdvanced ovarian cancerCTL precursor frequenciesIntracellular cytokine expressionT lymphocyte responsesHuman lymphocyte antigenGeneration of CA125-specific cytotoxic T lymphocytes in human leukocyte antigen-A2.1-positive healthy donors and patients with advanced ovarian cancer
Bellone S, Anfossi S, O'Brien TJ, Cannon MJ, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Generation of CA125-specific cytotoxic T lymphocytes in human leukocyte antigen-A2.1-positive healthy donors and patients with advanced ovarian cancer. American Journal Of Obstetrics And Gynecology 2008, 200: 75.e1-75.e10. PMID: 18976739, DOI: 10.1016/j.ajog.2008.08.014.Peer-Reviewed Original ResearchConceptsPeptide-specific cytotoxic T lymphocytesCytotoxic T lymphocytesHuman leukocyte antigenLeukocyte antigenOvarian cancerT lymphocytesHuman cytotoxic T-lymphocyte responsesCytotoxic T-lymphocyte precursor frequenciesNatural killer-sensitive targetsPeptide-loaded target cellsType 1 cytokine profileCytotoxic T lymphocyte responsesT lymphocyte precursor frequenciesPotential immunogenic peptidesAdvanced ovarian cancerClass I antibodiesIntracellular cytokine expressionT lymphocyte responsesPositive healthy donorsInterferon-gamma productionT lymphocyte populationsPeripheral blood leukocytesCytokine profileELISPOT assayCytokine expression
2004
Discrimination between uterine serous papillary carcinomas and ovarian serous papillary tumours by gene expression profiling
Santin AD, Zhan F, Bellone S, Palmieri M, Cane S, Gokden M, Roman JJ, O'Brien TJ, Tian E, Cannon MJ, Shaughnessy J, Pecorelli S. Discrimination between uterine serous papillary carcinomas and ovarian serous papillary tumours by gene expression profiling. British Journal Of Cancer 2004, 90: 1814-1824. PMID: 15208622, PMCID: PMC2409747, DOI: 10.1038/sj.bjc.6601791.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCarcinoma, PapillaryCells, CulturedCystadenocarcinoma, SerousDiagnosis, DifferentialFemaleFlow CytometryGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunohistochemistryMiddle AgedOligonucleotide Array Sequence AnalysisOvarian NeoplasmsReceptor, ErbB-2Reverse Transcriptase Polymerase Chain ReactionUterine NeoplasmsConceptsUterine serous papillary carcinomaGene expressionOverexpressed genesSerous papillary carcinomaGene expression fingerprintGene expression profilingHuman genesC-erbB2 geneExpression fingerprintsMolecular basisExpression profilingPapillary carcinomaOligonucleotide microarraysExpression productsQuantitative RT-PCRGenesClinical tissue samplesProbe setsTwo-fold differenceMore effective treatment modalitiesEffective treatment modalitySerous papillary tumorsPlasminogen activator inhibitorDifferent biological behaviorDevelopment of novelRestoration of tumor specific human leukocyte antigens class I‐restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer
Santin AD, Bellone S, Palmieri M, Bossini B, Cane' S, Bignotti E, Roman JJ, Cannon MJ, Pecorelli S. Restoration of tumor specific human leukocyte antigens class I‐restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer. International Journal Of Gynecological Cancer 2004, 14: 64-75. PMID: 14764031, DOI: 10.1111/j.1048-891x.2004.014175.x.Peer-Reviewed Original ResearchConceptsPeripheral blood lymphocytesAdvanced ovarian cancerAdvanced ovarian cancer patientsDendritic cellsOvarian cancer patientsOvarian cancerT cellsCancer patientsClass ILymphoblastoid cell linesTumor antigen-loaded dendritic cellsTumor lysate-pulsed dendritic cellsTumor-specific T-cell responsesAutologous ovarian cancer cellsAutologous tumor target cellsDC stimulationLysate-pulsed dendritic cellsType 1 cytokine biasAntigen-loaded dendritic cellsAnti-HLA class IAutologous Epstein-Barr virusIFN-gamma-positive cellsSpecific human leukocyte antigenProfessional antigen presenting cellsAdoptive T-cell immunotherapy
2002
Novel immunotherapeutic strategies in gynecologic oncology. Dendritic cell-based immunotherapy for ovarian cancer.
Santin AD, Bellone S, Underwood LJ, O'Brien TJ, Ravaggi A, Pecorelli S, Cannon MJ. Novel immunotherapeutic strategies in gynecologic oncology. Dendritic cell-based immunotherapy for ovarian cancer. Minerva Obstetrics And Gynecology 2002, 54: 133-44. PMID: 12032451.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntigens, NeoplasmCancer VaccinesChildClinical Trials as TopicCombined Modality TherapyDendritic CellsFemaleGPI-Linked ProteinsHumansImmunohistochemistryImmunotherapyKallikreinsMatrix Metalloproteinase 7Membrane ProteinsNeoplasm MetastasisOvarian NeoplasmsSerine EndopeptidasesT-Lymphocytes, CytotoxicTumor Cells, CulturedConceptsTumor antigensOvarian cancerChemotherapy-resistant ovarian cancerOvarian tumor-associated antigensDendritic cell-based immunotherapyTumor-specific immune responsesEffective tumor antigensTherapeutic DC vaccinationNovel immunotherapeutic strategiesStandard treatment modalityCell-based immunotherapyOvarian tumor antigenSpecific immune responseTumor-associated antigensPotential of DCDC vaccinationImmunotherapeutic strategiesDendritic cellsCancer vaccinationCancer patientsGynecologic oncologyTreatment modalitiesNatural adjuvantImmune responseAntigen preparations
2001
Increased levels of interleukin‐10 and transforming growth factor‐β in the plasma and ascitic fluid of patients with advanced ovarian cancer
Santin A, Bellone S, Ravaggi A, Roman J, Smith C, Pecorelli S, Cannon M, Parham G. Increased levels of interleukin‐10 and transforming growth factor‐β in the plasma and ascitic fluid of patients with advanced ovarian cancer. BJOG An International Journal Of Obstetrics & Gynaecology 2001, 108: 804-808. PMID: 11510703, DOI: 10.1111/j.1471-0528.2001.00206.x.Peer-Reviewed Original ResearchConceptsOvarian cancer patientsAdvanced ovarian cancerIL-10Cancer patientsOvarian cancerAscitic fluidPlasma levelsPeritoneal fluidAdvanced ovarian cancer patientsElevated TGF-beta levelsImmunosuppressive cytokine IL-10Anti-tumor immune functionDetectable IL-10TGF-beta levelsCytokine IL-10Time of surgeryDepartment of ObstetricsTGF-beta releasePlasma samplesNormal female controlsSensitive enzyme-linked immunosorbentEnzyme-linked immunosorbentImmunosuppressive cytokinesInterleukin-10Prospective studyPhenotypic and Functional Analysis of Tumor-Infiltrating Lymphocytes Compared with Tumor-Associated Lymphocytes from Ascitic Fluid and Peripheral Blood Lymphocytes in Patients with Advanced Ovarian Cancer
Santin AD, Hermonat PL, Ravaggi A, Bellone S, Roman JJ, Smith CV, Pecorelli S, Radominska-Pandya A, Cannon MJ, Parham GP. Phenotypic and Functional Analysis of Tumor-Infiltrating Lymphocytes Compared with Tumor-Associated Lymphocytes from Ascitic Fluid and Peripheral Blood Lymphocytes in Patients with Advanced Ovarian Cancer. Gynecologic And Obstetric Investigation 2001, 51: 254-261. PMID: 11408737, DOI: 10.1159/000058060.Peer-Reviewed Original ResearchConceptsTumor-associated lymphocytesTumor-infiltrating lymphocytesPeripheral blood lymphocytesAdvanced ovarian cancerType 1 cytokinesT cellsBlood lymphocytesOvarian cancerAscitic fluidAntigen-experienced T lymphocytesActivation markers HLA-DREarly activation markers CD25Markers HLA-DRType 2 cytokinesActivation markers CD25Major leukocyte populationsIL-2 pathwayIL-2 receptorFunction of lymphocytesIL-2 productionLow surface expressionLymphocyte subsetsHigher proportionHLA-DRActivation markers
2000
Induction of Ovarian Tumor-Specific CD8+ Cytotoxic T Lymphocytes by Acid-Eluted Peptide-Pulsed Autologous Dendritic Cells
SANTIN A, BELLONE S, RAVAGGI A, PECORELLI S, CANNON M, PARHAM G. Induction of Ovarian Tumor-Specific CD8+ Cytotoxic T Lymphocytes by Acid-Eluted Peptide-Pulsed Autologous Dendritic Cells. Obstetrics And Gynecology 2000, 96: 422-430. DOI: 10.1097/00006250-200009000-00019.Peer-Reviewed Original ResearchConceptsAutologous tumor cellsAdvanced ovarian cancerT lymphocyte responsesCytotoxic T lymphocytesDendritic cellsT lymphocytesOvarian cancerTumor cellsLymphocyte responsesTumor-specific cytotoxic T-cell responseTumour peptide-pulsed dendritic cellsAutologous ovarian cancer cellsAutologous ovarian tumor cellsPeptide-pulsed dendritic cellsAnti-HLA class ICytotoxic T lymphocyte responsesCytotoxic T cell responsesTwo-color flow cytometric analysisPeripheral blood mononuclear cellsHLA-A2 monoclonal antibodyClass IAutologous dendritic cellsTumor-specific CD8T cell responsesStrong cytolytic activityIn vitro induction of tumor-specific human lymphocyte antigen class I–restricted CD8+ cytotoxic T lymphocytes by ovarian tumor antigen–pulsed autologous dendritic cells from patients with advanced ovarian cancer
Santin A, Hermonat P, Ravaggi A, Bellone S, Pecorelli S, Cannon M, Parham G. In vitro induction of tumor-specific human lymphocyte antigen class I–restricted CD8+ cytotoxic T lymphocytes by ovarian tumor antigen–pulsed autologous dendritic cells from patients with advanced ovarian cancer. American Journal Of Obstetrics And Gynecology 2000, 183: 601-609. PMID: 10992180, DOI: 10.1067/mob.2000.107097.Peer-Reviewed Original ResearchConceptsAutologous tumor cellsAdvanced ovarian cancerTumor lysate-pulsed dendritic cellsLysate-pulsed dendritic cellsCytotoxic T lymphocytesDendritic cellsAntigen class IT lymphocytesOvarian cancerTumor cellsAutologous Epstein-Barr virus-transformed lymphoblastoid cell linesTumor-specific cytotoxic T-cell responseAutologous ovarian cancer cellsAutologous ovarian tumor cellsHuman leukocyte antigen (HLA) class IAdvanced stage ovarian cancerCytotoxic T lymphocyte responsesClass I monoclonal antibodiesCytotoxic T cell responsesVirus-transformed lymphoblastoid cell linesEpstein-Barr virus-transformed lymphoblastoid cell linesClass IHuman lymphocyte antigen class IAutologous dendritic cellsHigh cytotoxic activityInduction of ovarian tumor-specific CD8+ cytotoxic T lymphocytes by acid-eluted peptide-pulsed autologous dendritic cells.
Santin A, Bellone S, Ravaggi A, Pecorelli S, Cannon M, Parham G. Induction of ovarian tumor-specific CD8+ cytotoxic T lymphocytes by acid-eluted peptide-pulsed autologous dendritic cells. Obstetrics And Gynecology 2000, 96: 422-30. PMID: 10960637, DOI: 10.1016/s0029-7844(00)00916-9.Peer-Reviewed Original ResearchConceptsAutologous tumor cellsAdvanced ovarian cancerPeptide-pulsed dendritic cellsT lymphocyte responsesDendritic cellsT lymphocytesOvarian cancerTumor cellsLymphocyte responsesTumor-specific cytotoxic T-cell responsePeptide-pulsed autologous dendritic cellsTumour peptide-pulsed dendritic cellsAutologous ovarian cancer cellsAutologous ovarian tumor cellsAnti-HLA class ICytotoxic T lymphocyte responsesCytotoxic T cell responsesTwo-color flow cytometric analysisPeripheral blood mononuclear cellsHLA-A2 monoclonal antibodyClass IAutologous dendritic cellsTumor-specific CD8T cell responsesStrong cytolytic activity