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 carcinomaRandomized 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/mutationCervical 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
2019
Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy
Zammataro L, Lopez S, Bellone S, Pettinella F, Bonazzoli E, Perrone E, Zhao S, Menderes G, Altwerger G, Han C, Zeybek B, Bianchi A, Manzano A, Manara P, Cocco E, Buza N, Hui P, Wong S, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Odicino F, Pecorelli S, Donzelli C, Ardighieri L, Angioli R, Raspagliesi F, Scambia G, Choi J, Dong W, Bilguvar K, Alexandrov LB, Silasi DA, Huang GS, Ratner E, Azodi M, Schwartz PE, Pirazzoli V, Stiegler AL, Boggon TJ, Lifton RP, Schlessinger J, Santin AD. Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 22730-22736. PMID: 31624127, PMCID: PMC6842590, DOI: 10.1073/pnas.1911385116.Peer-Reviewed Original ResearchConceptsPI3K/AKT/mTOR pathwaySquamous cell carcinomaWhole-exome sequencingAKT/mTOR pathwayPrimary cervical cancer cell linesPIK3CA inhibitorsRecurrent cervical cancer patientsMTOR pathwayCombination of copanlisibCervical cancer patientsPI3K/Akt/mTORCervical cancer xenograftsRegression of tumorsCervical cancer cell linesCervical tumor cell linesSingle nucleotide variantsWild-type tumorsRecurrent somatic missense mutationsAkt/mTORCell linesPan-HERCancer cell linesTypes 16/18Cervical cancerCancer patientsPARP-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 activityUterine Artery–sparing Minimally Invasive Radical Trachelectomy: A Case Report and Review of the Literature
Kim S, Chung S, Azodi M, Menderes G. Uterine Artery–sparing Minimally Invasive Radical Trachelectomy: A Case Report and Review of the Literature. Journal Of Minimally Invasive Gynecology 2019, 26: 1389-1395. PMID: 31173940, DOI: 10.1016/j.jmig.2019.05.017.Peer-Reviewed Original ResearchConceptsInvasive radical trachelectomyRadical trachelectomyUterine arteriesCase reportFuture fertilityFertility outcomesUterine arterial blood flowEarly-stage cervical cancerStage IB1 diseaseSquamous cell histologySquamous cell carcinomaArterial blood flowRobotic-assisted approachesMajority of casesIB1 diseaseNormal mensesObstetric outcomesCell histologyPatient demographicsBlood lossOperative timeCervical cancerRecurrence rateCell carcinomaMean age
2015
Factors Predictive of Improved Survival in Patients With Brain Metastases From Gynecologic Cancer
Gressel GM, Lundsberg LS, Altwerger G, Katchi T, Azodi M, Schwartz PE, Ratner ES, Damast S. Factors Predictive of Improved Survival in Patients With Brain Metastases From Gynecologic Cancer. International Journal Of Gynecological Cancer 2015, 25: 1711-1716. PMID: 26332394, PMCID: PMC4623851, DOI: 10.1097/igc.0000000000000554.Peer-Reviewed Original ResearchConceptsBrain metastatic diseaseEpithelial ovarian cancerBrain metastasesEndometrial cancerCervical cancerGynecologic cancerSurgical resectionTwo-year overall survival ratesLargest single-institution experienceSingle institution experienceOverall survival rateOverall survival dataMedian survival timeSignificant hazard ratioLong-term survivalHazard ratioMetastatic diseaseOverall survivalImproved survivalRetrospective reviewIntracranial metastasesPalliative carePoor prognosisCancer increasesFactors Predictive
2012
Downregulation of membrane complement inhibitors CD55 and CD59 by siRNA sensitises uterine serous carcinoma overexpressing Her2/neu to complement and antibody-dependent cell cytotoxicity in vitro: implications for trastuzumab-based immunotherapy
Bellone S, Roque D, Cocco E, Gasparrini S, Bortolomai I, Buza N, Abu-Khalaf M, Silasi DA, Ratner E, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Downregulation of membrane complement inhibitors CD55 and CD59 by siRNA sensitises uterine serous carcinoma overexpressing Her2/neu to complement and antibody-dependent cell cytotoxicity in vitro: implications for trastuzumab-based immunotherapy. British Journal Of Cancer 2012, 106: 1543-1550. PMID: 22531721, PMCID: PMC3341945, DOI: 10.1038/bjc.2012.132.Peer-Reviewed Original ResearchAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityCD55 AntigensCD59 AntigensComplement ActivationCystadenocarcinoma, SerousCytotoxicity, ImmunologicDown-RegulationFemaleFlow CytometryHumansIn Situ Hybridization, FluorescenceMembrane Cofactor ProteinMiddle AgedPrognosisReal-Time Polymerase Chain ReactionReceptor, ErbB-2RNA, Small InterferingTrastuzumabUterine Cervical Neoplasms
2011
The significance of perineural invasion in early-stage cervical cancer
ElSahwi KS, Barber E, Illuzzi J, Buza N, Ratner E, Silasi DA, Santin AD, Azodi M, Schwartz PE, Rutherford TJ. The significance of perineural invasion in early-stage cervical cancer. Gynecologic Oncology 2011, 123: 561-564. PMID: 21968340, DOI: 10.1016/j.ygyno.2011.08.028.Peer-Reviewed Original ResearchConceptsEarly cervical cancerPerineural invasionCervical cancerRisk factorsAdjuvant therapyEarly-stage cervical cancer patientsEarly-stage cervical cancerMultiple high-risk factorsAdjusted hazard ratioIndependent risk factorRetrospective chart reviewLymphovascular space invasionCervical cancer patientsLarger tumor sizeHigh-risk factorsChart reviewHazard ratioCervical stromaParametrial invasionWorse prognosisPoor prognosisSpace invasionTumor sizeMean ageTumor extensionCervical 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
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 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
2008
Cervical carcinosarcoma: a case report.
Abidi A, Menn K, Sherman A, Konia T, Azodi M. Cervical carcinosarcoma: a case report. The Journal Of Reproductive Medicine 2008, 53: 138-40. PMID: 18357808.Peer-Reviewed Original ResearchConceptsCervical carcinosarcomaUterine corpusGood overall prognosisFemale genital tractPelvic radiation treatmentRecurrent diseaseOverall prognosisPostoperative radiationSurgical resectionImproved survivalBetter prognosisUterine cervixPoor prognosisCase reportMultimodal therapyRare neoplasmGenital tractEarly diagnosisCarcinosarcomaRadiation treatmentPrognosisTreatmentEarly stagesResectionCervix
2005
Adenoid cystic carcinoma of the cervix
Koyfman SA, Abidi A, Ravichandran P, Higgins SA, Azodi M. Adenoid cystic carcinoma of the cervix. Gynecologic Oncology 2005, 99: 477-480. PMID: 16139349, DOI: 10.1016/j.ygyno.2005.06.063.Peer-Reviewed Original ResearchMeSH KeywordsAdultCarcinoma, Adenoid CysticFemaleHumansRadiotherapy, AdjuvantUterine Cervical NeoplasmsConceptsCystic carcinomaStage IBHistologic featuresAggressive local therapyType III hysterectomyVaginal cuff radiationEvidence of diseaseStandardized treatment protocolSquamous cell carcinomaExternal beam radiotherapyLocal therapyAggressive neoplasmCell carcinomaTreatment protocolBeam radiotherapyHigh riskCervixCarcinomaAsian femalesPatientsIBHysterectomyRecurrenceNeoplasmsRadiotherapy