2005
Therapeutic vaccines for cervical cancer: dendritic cell-based immunotherapy.
Santin AD, Bellone S, Roman JJ, Burnett A, Cannon MJ, Pecorelli S. Therapeutic vaccines for cervical cancer: dendritic cell-based immunotherapy. Current Pharmaceutical Design 2005, 11: 3485-500. PMID: 16248803, DOI: 10.2174/138161205774414565.Peer-Reviewed Original ResearchMeSH KeywordsCancer VaccinesDendritic CellsFemaleHumansImmunotherapyPapillomaviridaeUterine Cervical NeoplasmsConceptsCervical cancer patientsT cell responsesDendritic cellsCervical cancerCancer patientsE7 oncoproteinsLate-stage cervical cancer patientsTumor-specific T-cell responsesImmune systemCell responsesPowerful antigen-presenting cellsDendritic cell-based immunotherapyPrimary T cell responsesCell-mediated immune responsesAutologous dendritic cellsTherapeutic HPV vaccinesTreatment-induced immunosuppressionPrimary radiation therapyHuman papillomavirus infectionAdvanced cervical cancerCell-based immunotherapyTumor-specific target antigensAntigen-presenting cellsImportant risk factorGold standard treatmentGene expression profiles of primary HPV16- and HPV18-infected early stage cervical cancers and normal cervical epithelium: identification of novel candidate molecular markers for cervical cancer diagnosis and therapy
Santin AD, Zhan F, Bignotti E, Siegel ER, Cané S, Bellone S, Palmieri M, Anfossi S, Thomas M, Burnett A, Kay HH, Roman JJ, O'Brien TJ, Tian E, Cannon MJ, Shaughnessy J, Pecorelli S. Gene expression profiles of primary HPV16- and HPV18-infected early stage cervical cancers and normal cervical epithelium: identification of novel candidate molecular markers for cervical cancer diagnosis and therapy. Virology 2005, 331: 269-291. PMID: 15629771, DOI: 10.1016/j.virol.2004.09.045.Peer-Reviewed Original ResearchConceptsTissue factor pathway inhibitor-2Normal cervical keratinocytesCDKN2A/p16V-myb myeloblastosis viral oncogene homologDifferential expressionMyeloblastosis viral oncogene homologE2F transcription factor 1Cyclin-dependent kinase inhibitor 2AGene expression profilesMesoderm-specific transcriptNovel candidate molecular markersNovel molecular featuresGene expression dataQuantitative real-time PCRSerine proteinase inhibitorTranscription factor 1V-mybDUTP pyrophosphataseProstaglandin E synthaseTopoisomerase II alphaCandidate molecular markersForkhead box M1Growth factor alphaOligonucleotide microarraysExpression profiles
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
2000
Interleukin-10 Increases Th1 Cytokine Production and Cytotoxic Potential in Human Papillomavirus-Specific CD8+ Cytotoxic T Lymphocytes
Santin A, Hermonat P, Ravaggi A, Bellone S, Pecorelli S, Roman J, Parham G, Cannon M. Interleukin-10 Increases Th1 Cytokine Production and Cytotoxic Potential in Human Papillomavirus-Specific CD8+ Cytotoxic T Lymphocytes. Journal Of Virology 2000, 74: 4729-4737. PMID: 10775611, PMCID: PMC111995, DOI: 10.1128/jvi.74.10.4729-4737.2000.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedCytokinesCytotoxicity, ImmunologicFemaleFlow CytometryHistocompatibility Antigens Class IHumansInterleukin-10Interleukin-2Lymphocyte ActivationMembrane GlycoproteinsPapillomaviridaePapillomavirus InfectionsPerforinPore Forming Cytotoxic ProteinsTh1 CellsT-Lymphocytes, CytotoxicTumor Cells, CulturedTumor Virus InfectionsUterine Cervical NeoplasmsConceptsIL-10IL-2Immunosuppressive cytokinesT lymphocytesSolid-phase anti-CD3 antibodyTumor necrosis factor alphaIntracellular perforin levelsTh1 cytokine secretionAutologous tumor cellsTime pointsTumor-specific CTLsTh1 cytokine productionCervical cancer patientsCytotoxic activityCytotoxic T lymphocytesNecrosis factor alphaT cell proliferationAnti-CD3 antibodyIFN-gamma expressionFluorescence-activated cell sorterGrowth factor betaIL-2 expressionLater time pointsAdoptive transfusionCD56 moleculesDevelopment, 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 lymphocytesBinding of the human papillomavirus type 16 E7 oncoprotein and the adeno-associated virus Rep78 major regulatory protein in vitro and in yeast and the potential for downstream effects.
Hermonat PL, Santin AD, Zhan D. Binding of the human papillomavirus type 16 E7 oncoprotein and the adeno-associated virus Rep78 major regulatory protein in vitro and in yeast and the potential for downstream effects. Human Virology 2000, 3: 113-24. PMID: 10881991.Peer-Reviewed Original ResearchMeSH KeywordsAlanineBinding SitesBlotting, WesternChromatography, AffinityDependovirusDNA PrimersDNA, ComplementaryDNA, ViralDNA-Binding ProteinsHumansOncogene Proteins, ViralPapillomaviridaePapillomavirus E7 ProteinsProtein BindingRecombinant Fusion ProteinsTATA-Binding Protein Associated FactorsTATA-Box Binding ProteinTranscription Factor TFIIDTranscription FactorsViral ProteinsYeastsConceptsAAV life cycleHuman papillomavirusTerminal repeat DNACompetitive affinity chromatographyCancer-promoting activityRep78E7 oncoproteinsAAVRep78 proteinDownstream effectsHPV-16 E7 oncoproteinSeries of aminoHuman papillomavirus type 16 E7 oncoproteinHPV 16/18Cervical cancerHPV 16Variety of proteinsType 1Bovine papillomavirus type 1P97 promoterOncogenic transformationPapillomavirus type 1AdenoPotential downstream effectsDosage-dependent manner
1999
Binding of the Human Papillomavirus Type 16 p97 Promoter by the Adeno-associated Virus Rep78 Major Regulatory Protein Correlates with Inhibition*
Zhan D, Santin A, Liu Y, Parham G, Li C, Meyers C, Hermonat P. Binding of the Human Papillomavirus Type 16 p97 Promoter by the Adeno-associated Virus Rep78 Major Regulatory Protein Correlates with Inhibition*. Journal Of Biological Chemistry 1999, 274: 31619-31624. PMID: 10531369, DOI: 10.1074/jbc.274.44.31619.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBovine papillomavirus 1Cell Transformation, NeoplasticCell Transformation, ViralChromatography, AffinityColony-Forming Units AssayDependovirusDNA-Binding ProteinsGene Expression Regulation, ViralMolecular Sequence DataMutationOncogene Proteins, ViralPapillomaviridaePromoter Regions, GeneticProtein BindingRepetitive Sequences, Nucleic AcidRepressor ProteinsViral ProteinsInduction 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 responses
1998
Radiation‐enhanced expression of E6/E7 transforming oncogenes of human papillomavirus‐16 in human cervical carcinoma
Santin A, Hermonat P, Ravaggi A, Chiriva‐Internati M, Pecorelli S, Parham G. Radiation‐enhanced expression of E6/E7 transforming oncogenes of human papillomavirus‐16 in human cervical carcinoma. Cancer 1998, 83: 2346-2352. PMID: 9840534, DOI: 10.1002/(sici)1097-0142(19981201)83:11<2346::aid-cncr14>3.0.co;2-g.Peer-Reviewed Original ResearchConceptsE6/E7 oncoproteinsMHC class ICervical carcinoma cell linesCarcinoma cell linesCervical carcinomaDose-dependent mannerE6/E7High dosesE7 oncoproteinsSiHa cell lineClass IRadiation therapyMajor histocompatibility complex restriction elementCell linesRadiation-induced drug resistanceHigh-risk HPV genotypesHPV-positive cervical carcinoma cell linesTumor cellsE6/E7 oncogenesE7 oncoprotein expressionE7 viral proteinsHuman papillomavirus infectionImportant risk factorTumor rejection antigensHuman papillomavirus 16
1997
Adeno-Associated Virus Rep78 Inhibits Oncogenic Transformation of Primary Human Keratinocytes by a Human Papillomavirus Type 16-rasChimeric
Hermonat PL, Plott RT, Santin AD, Parham GP, Flick JT. Adeno-Associated Virus Rep78 Inhibits Oncogenic Transformation of Primary Human Keratinocytes by a Human Papillomavirus Type 16-rasChimeric. Gynecologic Oncology 1997, 66: 487-494. PMID: 9299265, DOI: 10.1006/gyno.1997.4789.Peer-Reviewed Original ResearchConceptsHuman papillomavirusCervical cancerCervical carcinogenesisPapillomavirus typesHPV 16/18 infectionHuman papillomavirus typesHuman papillomavirus type 16Primary human foreskin keratinocytesCell typesHPV-16 p97 promoterPapillomavirus type 16Ability of AAVPrimary human keratinocytesSeroepidemiologic studiesInverse associationHuman foreskin keratinocytesVirus infectionType 16Host cell typesTransient CAT assaysType 1P97 promoterOncogenic transformationForeskin keratinocytesHuman keratinocytes