2024
Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)
Sheth S, Oh J, Bellone S, Siegel E, Greenman M, Mutlu L, McNamara B, Pathy S, Clark M, Azodi M, Altwerger G, Andikyan V, Huang G, Ratner E, Kim D, Iwasaki A, Levi A, Buza N, Hui P, Flaherty S, Schwartz P, Santin A. Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147). Clinical Cancer Research 2024, 30: of1-of10. PMID: 38592381, DOI: 10.1158/1078-0432.ccr-23-3639.Peer-Reviewed Original ResearchConceptsRandomized phase II trialCD4/CD8 T cellsT cellsHPV clearanceArm BNo significant differenceClinical surveillanceRate of HPV clearanceSecondary outcomesPre-neoplastic cervical lesionsCervical intraepithelial neoplasiaT cell infiltrationT cell responsesSignificant differenceCIN3 patientsIntraepithelial neoplasiaArm ACervical lesionsImiquimod groupSurveillance armVaginal suppositoriesProspective trialsArm CHPV vaccinationImiquimod
2020
Derangements in HUWE1/c-MYC pathway confer sensitivity to the BET bromodomain inhibitor GS-626510 in uterine cervical carcinoma
Bonazzoli E, Bellone S, Zammataro L, Gnutti B, Guglielmi A, Pelligra S, Nagarkatti N, Manara P, Tymon-Rosario J, Zeybek B, Altwerger G, Menderes G, Han C, Ratner E, Silasi DA, Huang GS, Andikyan V, Azodi M, Schwartz PE, Santin AD. Derangements in HUWE1/c-MYC pathway confer sensitivity to the BET bromodomain inhibitor GS-626510 in uterine cervical carcinoma. Gynecologic Oncology 2020, 158: 769-775. PMID: 32600791, PMCID: PMC8253557, DOI: 10.1016/j.ygyno.2020.06.484.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsCell Line, TumorFemaleHumansImidazolesIn Situ Hybridization, FluorescenceIsoxazolesMiceMiddle AgedProteinsProto-Oncogene Proteins c-mycSignal TransductionTumor Suppressor ProteinsUbiquitin-Protein LigasesUterine Cervical NeoplasmsXenograft Model Antitumor AssaysYoung AdultConceptsC-myc expressionC-Myc pathwayTwice-daily oral dosesC-MycWestern blotChemotherapy-resistant diseaseUterine cervical carcinomaPotential therapeutic targetEffective therapeutic agentDose-response decreaseCC xenograftsCell line growthOral dosesCervical carcinomaPrimary tumorDeletion/mutationClinical studiesTherapeutic targetTherapeutic agentsNormal tissuesBET inhibitorsVivo activityQRT-PCRCell proliferationGene deletion/mutationPhase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002)
Santin AD, Deng W, Frumovitz M, Buza N, Bellone S, Huh W, Khleif S, Lankes HA, Ratner ES, O'Cearbhaill RE, Jazaeri AA, Birrer M. Phase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002). Gynecologic Oncology 2020, 157: 161-166. PMID: 31924334, PMCID: PMC7127981, DOI: 10.1016/j.ygyno.2019.12.034.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsRecurrent cervical cancerPD-L1 expressionPlatinum-based chemotherapyCervical cancerStable diseaseGrade 3 treatment-related adverse eventsGrade 4 treatment-related adverse eventsGrade 5 treatment-related adverse eventsECOG PS 0Prior systemic therapyRecurrent cervical carcinomaResponse/toxicitySingle-agent nivolumabSystemic chemotherapy regimenTolerability of nivolumabImmune checkpoint inhibitorsPercent of patientsAcceptable safety profilePhase II trialKey eligibility criteriaPhase II evaluationECOG PSNivolumab 3RECIST 1.1
2019
PARP-1 activity (PAR) determines the sensitivity of cervical cancer to olaparib
Bianchi A, Lopez S, Altwerger G, Bellone S, Bonazzoli E, Zammataro L, Manzano A, Manara P, Perrone E, Zeybek B, Han C, Menderes G, Ratner E, Silasi DA, Huang GS, Azodi M, Newberg JY, Pavlick DC, Elvin J, Frampton GM, Schwartz PE, Santin AD. PARP-1 activity (PAR) determines the sensitivity of cervical cancer to olaparib. Gynecologic Oncology 2019, 155: 144-150. PMID: 31434613, PMCID: PMC6788971, DOI: 10.1016/j.ygyno.2019.08.010.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsApoptosisCell Growth ProcessesCell Line, TumorDose-Response Relationship, DrugDrug Resistance, NeoplasmFemaleG2 Phase Cell Cycle CheckpointsHumansM Phase Cell Cycle CheckpointsMice, SCIDMiddle AgedPhthalazinesPiperazinesPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsUterine Cervical NeoplasmsXenograft Model Antitumor AssaysYoung AdultConceptsPoly (ADP-ribose) polymerase (PARP) inhibitorsCervical cancerCC cell linesCell linesPARP-1 activityOverall animal survivalMajor health problemCC cell growthXenograft tumor growthWestern blot assaysG2/M phaseVivo antitumor activityCC xenograftsCC patientsPreclinical activityPAR expressionCell cycle arrestOvarian cancerPrimary cell linesOlaparib treatmentUseful biomarkerHealth problemsTumor growthAnimal survivalOlaparib activityAdjuvant Hormonal Therapy for Low-Grade Endometrial Stromal Sarcoma
Deshmukh U, Black J, Perez-Irizarry J, Passarelli R, Levy K, Rostkowski A, Hui P, Rutherford TJ, Santin AD, Azodi M, Silasi DA, Ratner E, Litkouhi B, Schwartz PE. Adjuvant Hormonal Therapy for Low-Grade Endometrial Stromal Sarcoma. Reproductive Sciences 2019, 26: 600-608. PMID: 29843577, DOI: 10.1177/1933719118778801.Peer-Reviewed Original ResearchConceptsLow-grade endometrial stromal sarcomaRecurrence-free survivalStage I patientsEndometrial stromal sarcomaAromatase inhibitorsI patientsStage IIStromal sarcomaAdvanced low-grade endometrial stromal sarcomaMean recurrence-free survivalLonger recurrence-free survivalAdjuvant hormonal therapyMedian followProgestin groupUnderwent hysterectomyHormonal therapyDisease recurrenceSide effectsPatientsStage IProgestinsMonthsSarcomaDiseaseTreatment
2015
Use of Monsel solution to treat obstetrical hemorrhage: a review and comparison to other topical hemostatic agents
Miller DT, Roque DM, Santin AD. Use of Monsel solution to treat obstetrical hemorrhage: a review and comparison to other topical hemostatic agents. American Journal Of Obstetrics And Gynecology 2015, 212: 725-735. PMID: 25577672, PMCID: PMC4457701, DOI: 10.1016/j.ajog.2014.12.029.Peer-Reviewed Original ResearchMeSH KeywordsFemaleFerric CompoundsHemostaticsHumansPostpartum HemorrhagePregnancySulfatesYoung AdultConceptsTopical hemostatic agentsMonsel's solutionHemostatic agentsAbnormal placentationFuture fertilityFocal placenta accretaPelvic artery embolizationSuccessful uterine preservationExcessive blood lossTime of deliveryResource-poor nationsObstetric surgeryPeripartum hemorrhageUterine preservationArtery embolizationCesarean hysterectomyPlacenta accretaBalloon tamponadeBlood lossMaternal deathsObstetrical hemorrhageAdverse sequelaePlacental bedCompression suturesSide effects
2011
Serum Human Epididymis Protein 4 and Risk for Ovarian Malignancy Algorithm as New Diagnostic and Prognostic Tools for Epithelial Ovarian Cancer Management
Bandiera E, Romani C, Specchia C, Zanotti L, Galli C, Ruggeri G, Tognon G, Bignotti E, Tassi RA, Odicino F, Caimi L, Sartori E, Santin AD, Pecorelli S, Ravaggi A. Serum Human Epididymis Protein 4 and Risk for Ovarian Malignancy Algorithm as New Diagnostic and Prognostic Tools for Epithelial Ovarian Cancer Management. Cancer Epidemiology Biomarkers & Prevention 2011, 20: 2496-2506. PMID: 22028406, PMCID: PMC3237732, DOI: 10.1158/1055-9965.epi-11-0635.Peer-Reviewed Original ResearchConceptsHuman epididymis protein 4Epithelial ovarian cancerSerum human epididymis protein 4Independent prognostic factorOvarian Malignancy AlgorithmPrognostic factorsMalignancy AlgorithmProgression-free survivalLymph node involvementOvarian cancer managementPreoperative serum samplesProtein 4Ovarian benign cystsElevated CA125Node involvementPositive cytologyPostmenopausal womenPremenopausal womenMultivariable analysisMulticenter studyPrognostic valueAdvanced ageOvarian cancerBenign cystsObstetricians stage
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
Human Kallikrein 5
Bandiera E, Zanotti L, Bignotti E, Romani C, Tassi R, Todeschini P, Tognon G, Ragnoli M, Santin AD, Gion M, Pecorelli S, Ravaggi A. Human Kallikrein 5. International Journal Of Gynecological Cancer 2009, 19: 1015-1021. PMID: 19820362, DOI: 10.1111/igc.0b013e3181ab597f.Peer-Reviewed Original ResearchConceptsOvarian carcinomaBorderline tumorsHealthy controlsPathological lesionsKLK5 levelsSpontaneous humoral immune responseBenign pathological lesionsImmune-based therapiesOvarian borderline tumorsSera of patientsHumoral immune responseBenign pelvic massesOvarian cancer progressionPotential new biomarkersEnzyme-linked immunosorbentOvarian cancer detectionHealthy womenPelvic massHumoral responseAntibody responseObstetricians stageImmune responsePatientsNew biomarkersCarcinomaHuman Papillomavirus Type 16 (HPV-16) Virus-Like Particle L1-Specific CD8+ Cytotoxic T Lymphocytes (CTLs) Are Equally Effective as E7-Specific CD8+ CTLs in Killing Autologous HPV-16-Positive Tumor Cells in Cervical Cancer Patients: Implications for L1 Dendritic Cell-Based Therapeutic Vaccines
Bellone S, El-Sahwi K, Cocco E, Casagrande F, Cargnelutti M, Palmieri M, Bignotti E, Romani C, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Human Papillomavirus Type 16 (HPV-16) Virus-Like Particle L1-Specific CD8+ Cytotoxic T Lymphocytes (CTLs) Are Equally Effective as E7-Specific CD8+ CTLs in Killing Autologous HPV-16-Positive Tumor Cells in Cervical Cancer Patients: Implications for L1 Dendritic Cell-Based Therapeutic Vaccines. Journal Of Virology 2009, 83: 6779-6789. PMID: 19386711, PMCID: PMC2698533, DOI: 10.1128/jvi.02443-08.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCancer VaccinesCapsid ProteinsCell Line, TumorDendritic CellsFemaleGene Expression ProfilingHuman papillomavirus 16HumansMiddle AgedOncogene Proteins, ViralPapillomavirus E7 ProteinsPapillomavirus InfectionsRepressor ProteinsRNA, ViralT-Lymphocytes, CytotoxicUterine Cervical NeoplasmsYoung AdultConceptsCervical cancer patientsCytotoxic T lymphocytesAutologous tumor cellsCancer patientsDendritic cellsT lymphocytesL1 VLPsCervical cancerTumor cellsE7 RNADendritic cell-based therapeutic vaccineE7-specific cytotoxic T lymphocytesHPV-16 positive cervical cancerCell-mediated immune responsesExpression levelsAutologous dendritic cellsHPV-16 VLPPromising prophylactic vaccineE7-specific CD8Human papillomavirus infectionT lymphocyte responsesStrong cytolytic activityTreatment of patientsPeripheral blood lymphocytesPrimary cervical tumors