2024
Integrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix
Bellone S, Jeong K, Halle M, Krakstad C, McNamara B, Greenman M, Mutlu L, Demirkiran C, Hartwich T, Yang-Hartwich Y, Zipponi M, Buza N, Hui P, Raspagliesi F, Lopez S, Paolini B, Milione M, Perrone E, Scambia G, Altwerger G, Ravaggi A, Bignotti E, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Quick C, Angioli R, Terranova C, Zaidi S, Nandi S, Alexandrov L, Siegel E, Choi J, Schlessinger J, Santin A. Integrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2321898121. PMID: 38625939, PMCID: PMC11046577, DOI: 10.1073/pnas.2321898121.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingPatient-derived-xenograftsBase excision repairCopy number lossMultiregion whole-exome sequencingCopy number gainHigh-grade neuroendocrine carcinomaCNV analysisPhylogenetic analysisEvolutionary historyNeuroendocrine cervical cancerHuman papillomavirus DNAMutator phenotypeSensitivity to afatinibGenetic landscapeRecurrent mutationsRNA sequencingGene fusionsMutational landscape analysisExcision repairGenesMutationsPan-HERConsistent with deficiencyNeuroendocrine carcinoma
2020
Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan
Zeybek B, Manzano A, Bianchi A, Bonazzoli E, Bellone S, Buza N, Hui P, Lopez S, Perrone E, Manara P, Zammataro L, Altwerger G, Han C, Tymon-Rosario J, Menderes G, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin A. Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan. Scientific Reports 2020, 10: 973. PMID: 31969666, PMCID: PMC6976591, DOI: 10.1038/s41598-020-58009-3.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaSacituzumab govitecanTrop-2 expressionAntibody-drug conjugatesCell surface markersXenograft modelTrop-2Adenocarcinoma/adenosquamous carcinomaAnti-Trop-2 antibodyCell linesWeekly intravenous administrationSignificant tumor growth inhibitionCervical cancer patientsPrimary cervical cancerStrong diffuse stainingPrimary cervical tumorsCervical cancer cell linesEpithelial solid tumorsReal-time polymerase chain reactionTumor growth inhibitionHuman placental tissuePositive cell linesNegative cell linesVivo antitumor activityCancer cell lines
2011
Cervical carcinomas overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody
Varughese J, Cocco E, Bellone S, Ratner E, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Buza N, Pecorelli S, Santin AD. Cervical carcinomas overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody. American Journal Of Obstetrics And Gynecology 2011, 205: 567.e1-567.e7. PMID: 21889762, PMCID: PMC3224189, DOI: 10.1016/j.ajog.2011.06.093.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAntibodies, MonoclonalAntigens, NeoplasmBiomarkers, TumorCarcinoma, Squamous CellCell Adhesion MoleculesCell Line, TumorComplement System ProteinsDrug Resistance, NeoplasmDrug SynergismFemaleFlow CytometryGene Expression Regulation, NeoplasticHumansImmunoglobulin GInterleukin-2Killer Cells, NaturalReal-Time Polymerase Chain ReactionUterine Cervical NeoplasmsConceptsAntibody-dependent cell-mediated cytotoxicityAnti-Trop-2 antibodyTrop-2 expressionReal-time polymerase chain reactionCell surface markersCervical cancerPolymerase chain reactionHighest messenger RNA expressionCell-dependent cytotoxicityCell-mediated cytotoxicityNovel treatment optionsChromium release assaysConventional treatment modalitiesChain reactionComplement-dependent cytotoxicityEffects of interleukinMessenger RNA expressionLevel of cytotoxicityCancer refractoryCervical carcinomaTreatment optionsTreatment modalitiesIL-2Normal cervixRelease assaysExpression 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
Clostridium perfringens enterotoxin carboxy-terminal fragment is a novel tumor-homing peptide for human ovarian cancer
Cocco E, Casagrande F, Bellone S, Richter CE, Bellone M, Todeschini P, Holmberg JC, Fu HH, Montagna MK, Mor G, Schwartz PE, Arin-Silasi D, Azoudi M, Rutherford TJ, Abu-Khalaf M, Pecorelli S, Santin AD. Clostridium perfringens enterotoxin carboxy-terminal fragment is a novel tumor-homing peptide for human ovarian cancer. BMC Cancer 2010, 10: 349. PMID: 20598131, PMCID: PMC2908101, DOI: 10.1186/1471-2407-10-349.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma, Clear CellAnimalsCarcinoma, PapillaryCarcinoma, Squamous CellChlorocebus aethiopsClaudin-3Claudin-4Clostridium perfringensCystadenocarcinoma, SerousDrug Resistance, NeoplasmEnterotoxinsFemaleFibroblastsFlow CytometryHumansMembrane ProteinsMiceMice, SCIDOvarian NeoplasmsPeptide FragmentsReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSpheroids, CellularTissue DistributionTransplantation, HeterologousTumor Cells, CulturedUterine Cervical NeoplasmsVero CellsConceptsChemotherapy-resistant ovarian cancerClostridium perfringens enterotoxinOvarian cancerOvarian carcinoma cell linesClaudin-3Carcinoma cell linesNovel tumor-homing peptideCarboxy-terminal fragmentTumor cellsResistant ovarian cancer cell linesCell linesNew diagnostic tracersCPE peptideOvarian cancer cell linesResistant ovarian cancer cellsResistant ovarian carcinomaHuman ovarian cancerRelevant animal modelsOvarian tumor cellsOvarian cancer cellsChemotherapy-resistant ovarian cancer cellsHuman epithelial tumorsTime-dependent internalizationCancer cell linesBio-distribution studies
2008
Recurrent endometrial carcinoma regression with the use of the aromatase inhibitor anastrozole
Bellone S, Shah HR, McKenney JK, Stone PJ, Santin AD. Recurrent endometrial carcinoma regression with the use of the aromatase inhibitor anastrozole. American Journal Of Obstetrics And Gynecology 2008, 199: e7-e10. PMID: 18550023, DOI: 10.1016/j.ajog.2008.04.012.Peer-Reviewed Original Research
2004
The novel serine protease tumor-associated differentially expressed gene-14 (KLK8/Neuropsin/Ovasin) is highly overexpressed in cervical cancer
Cane' S, Bignotti E, Bellone S, Palmieri M, De Las Casas L, Roman JJ, Pecorelli S, Cannon MJ, O'Brien T, Santin AD. The novel serine protease tumor-associated differentially expressed gene-14 (KLK8/Neuropsin/Ovasin) is highly overexpressed in cervical cancer. American Journal Of Obstetrics And Gynecology 2004, 190: 60-66. PMID: 14749636, DOI: 10.1016/j.ajog.2003.07.020.Peer-Reviewed Original ResearchConceptsCervical cancer cell linesReverse transcriptase-polymerase chain reactionTranscriptase-polymerase chain reactionCancer cell linesCervical cancerCervical tumorsParaffin-embedded cervical cancer specimensPrimary cervical cancer cell linesCell linesPersistent cervical cancerNormal cervical epithelial cellsCervical cancer specimensCervical biopsy specimensChain reactionHuman cervical tumorsPrimary tumor cell linesCervical epithelial cellsCervical cancer therapyNovel molecular targetsGene 14Useful diagnostic toolFrequency of expressionPrimary adenocarcinomaStandard treatmentPolymerase chain reaction
2003
The novel serine protease tumor‐associated differentially expressed gene–15 (matriptase/MT‐SP1) is highly overexpressed in cervical carcinoma
Santin AD, Cane' S, Bellone S, Bignotti E, Palmieri M, De Las Casas LE, Anfossi S, Roman JJ, O'Brien T, Pecorelli S. The novel serine protease tumor‐associated differentially expressed gene–15 (matriptase/MT‐SP1) is highly overexpressed in cervical carcinoma. Cancer 2003, 98: 1898-1904. PMID: 14584072, DOI: 10.1002/cncr.11753.Peer-Reviewed Original ResearchIn vitro induction of tumor-specific HLA class I-restricted CD8+ cytotoxic T lymphocytes from patients with locally advanced breast cancer by tumor antigen-pulsed autologous dendritic cells11Supported in part by grants from the Arkansas Breast Cancer Research Program, the Arkansas Special Population Network (A-SPAN), and the Camillo Golgi Foundation, Brescia, Italy (to A.S.).
Kass R, Agha J, Bellone S, Palmieri M, Canè S, Bignotti E, Henry-Tillman R, Hutchins L, Cannon MJ, Klimberg S, Santin AD. In vitro induction of tumor-specific HLA class I-restricted CD8+ cytotoxic T lymphocytes from patients with locally advanced breast cancer by tumor antigen-pulsed autologous dendritic cells11Supported in part by grants from the Arkansas Breast Cancer Research Program, the Arkansas Special Population Network (A-SPAN), and the Camillo Golgi Foundation, Brescia, Italy (to A.S.). Journal Of Surgical Research 2003, 112: 189-197. PMID: 12888337, DOI: 10.1016/s0022-4804(03)00147-1.Peer-Reviewed Original ResearchConceptsAutologous tumor cellsAdvanced breast cancerHLA class IAntigen-pulsed dendritic cellsIntracellular cytokine expressionDendritic cellsBreast cancerFlow cytometric analysisTumor cellsCytokine expressionClass IT lymphocytesAutologous Epstein-Barr virus-transformed lymphoblastoid cell linesTumor antigen-pulsed dendritic cellsTumor lysate-pulsed dendritic cellsLysate-pulsed dendritic cellsPowerful antigen-presenting cellsTwo-color flow cytometric analysisCytometric analysisPeripheral blood mononuclear cellsSurface markersVirus-transformed lymphoblastoid cell linesEpstein-Barr virus-transformed lymphoblastoid cell linesColor flow cytometric analysisBreast Cancer Research Program
2002
Vaccination with HPV-18 E7–Pulsed Dendritic Cells in a Patient with Metastatic Cervical Cancer
Santin AD, Bellone S, Gokden M, Cannon MJ, Parham GP. Vaccination with HPV-18 E7–Pulsed Dendritic Cells in a Patient with Metastatic Cervical Cancer. New England Journal Of Medicine 2002, 346: 1752-1753. PMID: 12037163, DOI: 10.1056/nejm200205303462219.Peer-Reviewed Original Research
2001
Tumor-Infiltrating Lymphocytes Contain Higher Numbers of Type 1 Cytokine Expressors and DR+ T Cells Compared with Lymphocytes from Tumor Draining Lymph Nodes and Peripheral Blood in Patients with Cancer of the Uterine Cervix
Santin A, Ravaggi A, Bellone S, Pecorelli S, Cannon M, Parham G, Hermonat P. Tumor-Infiltrating Lymphocytes Contain Higher Numbers of Type 1 Cytokine Expressors and DR+ T Cells Compared with Lymphocytes from Tumor Draining Lymph Nodes and Peripheral Blood in Patients with Cancer of the Uterine Cervix. Gynecologic Oncology 2001, 81: 424-432. PMID: 11371133, DOI: 10.1006/gyno.2001.6200.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedCarcinoma, Squamous CellCD4-CD8 RatioCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCytokinesFemaleHLA-DR AntigensHumansImmunophenotypingInterferon-gammaInterleukin-2Interleukin-4Lymph NodesLymphocytesLymphocytes, Tumor-InfiltratingMiddle AgedNeoplasm StagingReceptors, Interleukin-2Th1 CellsTh2 CellsUterine Cervical NeoplasmsConceptsType 1 cytokinesLymph nodesPeripheral bloodT cellsTumor tissueLymphocyte subsetsStage IB-IIA cervical cancerAntigen-experienced T lymphocytesIB-IIA cervical cancerTumor draining lymph nodeActivation markers HLA-DREarly activation markers CD25Draining Lymph NodesMarkers HLA-DRType 2 cytokinesCervical cancer patientsRegional lymph nodesActivation markers CD25Tumor-Infiltrating LymphocytesMajor leukocyte populationsFunction of lymphocytesCervical tumor tissuesDifferent anatomical sitesHLA-DRUterine cervix
2000
Development, characterization and distribution of adoptively transferred peripheral blood lymphocytes primed by human papillomavirus 18 E7--pulsed autologous dendritic cells in a patient with metastatic adenocarcinoma of the uterine cervix.
Santin AD, Hermonat PL, Ravaggi A, Bellone S, Cowan C, Korourian S, Pecorelli S, Cannon MJ, Parham GP. Development, characterization and distribution of adoptively transferred peripheral blood lymphocytes primed by human papillomavirus 18 E7--pulsed autologous dendritic cells in a patient with metastatic adenocarcinoma of the uterine cervix. European Journal Of Gynaecological Oncology 2000, 21: 17-23. PMID: 10726612.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsAutologous dendritic cellsDendritic cellsT cellsMetastatic diseaseUterine cervixAutologous Epstein-Barr virus-transformed lymphoblastoid cellsNK-sensitive K562 cellsSerial gamma camera imagingTumor-specific T cellsTwo-color flow cytometric analysisPeripheral blood T cellsTumor cellsIntracellular cytokine productionAutologous tumor cellsExtensive metastatic diseaseInvasive cervical cancerTumor-specific CTLsIntracellular cytokine expressionEpstein-Barr virus-transformed lymphoblastoid cellsBlood mononuclear cellsTreatment of patientsBlood T cellsCytotoxic T cellsPeripheral blood lymphocytes
1999
Induction of Human Papillomavirus-Specific CD4+ and CD8+ Lymphocytes by E7-Pulsed Autologous Dendritic Cells in Patients with Human Papillomavirus Type 16- and 18-Positive Cervical Cancer
Santin A, Hermonat P, Ravaggi A, Chiriva-Internati M, Zhan D, Pecorelli S, Parham G, Cannon M. Induction of Human Papillomavirus-Specific CD4+ and CD8+ Lymphocytes by E7-Pulsed Autologous Dendritic Cells in Patients with Human Papillomavirus Type 16- and 18-Positive Cervical Cancer. Journal Of Virology 1999, 73: 5402-5410. PMID: 10364287, PMCID: PMC112596, DOI: 10.1128/jvi.73.7.5402-5410.1999.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaCarcinoma, Squamous CellCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DivisionDendritic CellsDNA-Binding ProteinsFemaleHistocompatibility TestingHLA-A AntigensHLA-B AntigensHLA-C AntigensHumansImmunophenotypingInterferon-gammaInterleukin-4Intracellular FluidK562 CellsOncogene Proteins, ViralPapillomaviridaePapillomavirus E7 ProteinsPapillomavirus InfectionsT-Lymphocytes, CytotoxicTumor Cells, CulturedTumor Virus InfectionsUterine Cervical NeoplasmsConceptsAutologous dendritic cellsAutologous tumor cellsDendritic cellsHuman papillomavirus type 16Cervical cancerLymphoblastoid cell linesPapillomavirus type 16HPV 16CTL populationsT cellsType 16Autologous Epstein-Barr virus-transformed lymphoblastoid cell linesAnti-HLA class II antibodiesAutologous tumor target cellsAnti-HLA class ICytotoxic T lymphocyte responsesTwo-color flow cytometric analysisVirus-transformed lymphoblastoid cell linesEpstein-Barr virus-transformed lymphoblastoid cell linesT cell proliferative responsesTumor cellsPotential tumor-specific targetClass II antibodiesIntracellular cytokine expressionT lymphocyte responsesSecretion of Vascular Endothelial Growth Factor in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix
SANTIN A, HERMONAT P, RAVAGGI A, PECORELLI S, CANNON M, PARHAM G. Secretion of Vascular Endothelial Growth Factor in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix. Obstetrics And Gynecology 1999, 94: 78-82. DOI: 10.1097/00006250-199907000-00015.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorSquamous cell carcinomaEndothelial growth factorVascular endothelial growth factor (VEGF) secretionSquamous cell linesUterine cervixCell carcinomaGrowth factor secretionGrowth factorFactor secretionCell linesSensitive enzyme-linked immunosorbentSignificant differencesEnzyme-linked immunosorbentCervical carcinoma cell linesImmunosuppressive cytokinesHistologic typeCervical cancerCarcinoma cell linesCervical tumorsBiologic behaviorHematogenous metastasisAdenocarcinomaCervixRadiation treatmentSecretion of vascular endothelial growth factor in adenocarcinoma and squamous cell carcinoma of the uterine cervix.
Santin A, Hermonat P, Ravaggi A, Pecorelli S, Cannon M, Parham G. Secretion of vascular endothelial growth factor in adenocarcinoma and squamous cell carcinoma of the uterine cervix. Obstetrics And Gynecology 1999, 94: 78-82. PMID: 10389722, DOI: 10.1016/s0029-7844(99)00282-3.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorSquamous cell carcinomaEndothelial growth factorVascular endothelial growth factor (VEGF) secretionSquamous cell linesUterine cervixCell carcinomaGrowth factor secretionGrowth factorFactor secretionCell linesSensitive enzyme-linked immunosorbentSignificant differencesEnzyme-linked immunosorbentCervical carcinoma cell linesImmunosuppressive cytokinesHistologic typeCervical cancerCarcinoma cell linesCervical tumorsBiologic behaviorHematogenous metastasisAdenocarcinomaCervixRadiation treatment
1997
Differential Transforming Growth Factor-β Secretion in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix
Santin A, Hermonat P, Hiserodt J, Fruehauf J, Schranz V, Barclay D, Pecorelli S, Parham G. Differential Transforming Growth Factor-β Secretion in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix. Gynecologic Oncology 1997, 64: 477-480. PMID: 9062154, DOI: 10.1006/gyno.1996.4579.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaCarcinoma, Squamous CellFemaleHumansTransforming Growth Factor betaTumor Cells, CulturedUterine Neoplasms
1996
Development and characterization of a clinically useful animal model of epithelial ovarian cancer in the Fischer 344 rat
Government. T, Rose, Tocco, Granger, DiSaia, Hamilton, Santin, Hiserodt. Development and characterization of a clinically useful animal model of epithelial ovarian cancer in the Fischer 344 rat. American Journal Of Obstetrics And Gynecology 1996, 175: 593-599. PMID: 8828419, DOI: 10.1053/ob.1996.v175.a73595.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAnimalsDisease Models, AnimalEpitheliumFemaleFlow CytometryHistocompatibility Antigens Class IHistocompatibility Antigens Class IIInjections, IntraperitonealIntercellular Adhesion Molecule-1MiceMice, NudeNeoplasm TransplantationOvarian NeoplasmsRatsRats, Inbred F344Tumor Cells, CulturedConceptsNuTu-19 cellsMajor histocompatibility complex class IEpithelial ovarian cancerHistocompatibility complex class IFischer 344 ratsComplex class IOvarian cancerCell surface antigensAnimal modelsAnimal survivalSurface antigenMajor histocompatibility complex class II antigensOvarian cancer animal modelKaplan-Meier survival analysisHuman ovarian epithelial carcinomaTumor cellsCell linesClass IClass II antigensExperimental animal modelsViable tumor cellsFemale athymic miceOvarian epithelial carcinomaParental tumor cellsUseful animal modelEffects of cytokines combined with high‐dose gamma irradiation on the expression of major histocompatibility complex molecules and intercellular adhesion molecule‐1 in human ovarian cancers
Santin A, Rose G, Hiserodt J, Fruehauf J, Eck L, Garcia R, Schranz V, Disaia P, Pecorelli S, Granger G. Effects of cytokines combined with high‐dose gamma irradiation on the expression of major histocompatibility complex molecules and intercellular adhesion molecule‐1 in human ovarian cancers. International Journal Of Cancer 1996, 65: 688-694. PMID: 8598323, DOI: 10.1002/(sici)1097-0215(19960301)65:5<688::aid-ijc21>3.0.co;2-2.Peer-Reviewed Original ResearchConceptsMHC class 1TNF-alphaAntigen expressionIFN-gammaFresh tumorsOvarian cell linesTumor cellsIntercellular adhesion molecule-1Cell linesICAM-1 antigen expressionHuman ovarian cancer cell linesOvarian cancer cell linesMajor histocompatibility complex moleculesICAM-1 antigenCytokines TNF-alphaClass 1Adhesion molecule-1Human ovarian cancerHuman ovarian tumorsEffects of cytokinesHuman ovarian cell linesRemoval of cytokinesICAM-1 surfaceHistocompatibility complex moleculesCancer cell lines