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/mutation
2017
Efficacy of neratinib in the treatment of HER2/neu-amplified epithelial ovarian carcinoma in vitro and in vivo
Menderes G, Bonazzoli E, Bellone S, Black JD, Lopez S, Pettinella F, Masserdotti A, Zammataro L, Litkouhi B, Ratner E, Silasi DA, Azodi M, Schwartz PE, Santin AD. Efficacy of neratinib in the treatment of HER2/neu-amplified epithelial ovarian carcinoma in vitro and in vivo. Medical Oncology 2017, 34: 91. PMID: 28397106, PMCID: PMC5896014, DOI: 10.1007/s12032-017-0956-8.Peer-Reviewed Original ResearchConceptsEpithelial ovarian carcinomaOvarian carcinoma xenograftsOvarian cancerOvarian carcinomaCarcinoma xenograftsPreclinical efficacyCell linesTumor cell linesHER2/neu expressionChemotherapy-resistant diseaseOvarian cancer cell linesAvailable treatment strategiesEfficacy of neratinibInhibits xenograft growthNovel therapeutic agentsPrimary tumor cell linesG0/G1 phaseCell cycle distributionCell signaling changesNeratinib treatmentCancer cell linesGynecologic malignanciesOverall survivalNeu expressionClinical trials
2016
Novel targeted therapies in uterine serous carcinoma, an aggressive variant of endometrial cancer.
Menderes G, Clark M, Santin AD. Novel targeted therapies in uterine serous carcinoma, an aggressive variant of endometrial cancer. Discovery Medicine 2016, 21: 293-303. PMID: 27232515.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntineoplastic AgentsClass I Phosphatidylinositol 3-KinasesCyclin ECystadenocarcinoma, SerousEndometrial NeoplasmsEpothilonesExomeFemaleHumansMolecular Targeted TherapyMutationNeoplasm Recurrence, LocalOncogene ProteinsPrognosisProtein Kinase InhibitorsProtein Phosphatase 2RadioimmunotherapyReceptor, ErbB-2Sequence Analysis, DNASignal TransductionTOR Serine-Threonine KinasesTubulin ModulatorsTumor Suppressor Protein p53Uterine NeoplasmsVascular Endothelial Growth Factor AConceptsUterine serous carcinomaEndometrial cancerSerous carcinomaTreatment of USCPIK3CA/AKT/mTOREndometrial cancer casesRecent whole-exome sequencing studiesHER2/neu geneNovel therapeutic targetAkt/mTORBiologic therapyAggressive variantDismal prognosisAggressive subtypeWhole-exome sequencing studiesCancer casesTherapeutic targetSubsequent deathDriver mutationsNeu geneGain of functionCarcinomaTherapyCancerSequencing studies
2014
Afatinib demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro and in vivo
Schwab CL, Bellone S, English DP, Roque DM, Lopez S, Cocco E, Nicoletti R, Bortolomai I, Bonazzoli E, Ratner E, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Santin AD. Afatinib demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro and in vivo. British Journal Of Cancer 2014, 111: 1750-1756. PMID: 25268372, PMCID: PMC4453741, DOI: 10.1038/bjc.2014.519.Peer-Reviewed Original ResearchMeSH KeywordsAdultAfatinibAgedAged, 80 and overAnimalsApoptosisCell CycleCell ProliferationCystadenocarcinoma, SerousEndometrial NeoplasmsFemaleHumansImmunoenzyme TechniquesIn Situ Hybridization, FluorescenceIn Vitro TechniquesMiceMice, SCIDMiddle AgedPhosphorylationQuinazolinesReceptor, ErbB-2Signal TransductionTumor Cells, CulturedUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaUSC cell linesHER2/neu gene amplificationNeu gene amplificationAfatinib exposureOverall survivalCell linesHER2/neu amplificationEfficacy of afatinibPrimary USC cell linesGrowth of HER2Treatment of HER2Serous endometrial cancerErbB tyrosine kinase inhibitorsHER2/neuTyrosine kinase inhibitorsGene amplificationFlow cytometry assayCell cycle distributionUSC xenograftsEndometrial cancerSerous carcinomaUterine cancerAggressive formTumor xenograftsNeratinib shows efficacy in the treatment of HER2/neu amplified uterine serous carcinoma in vitro and in vivo
Schwab CL, English DP, Roque DM, Bellone S, Lopez S, Cocco E, Nicoletti R, Rutherford TJ, Schwartz PE, Santin AD. Neratinib shows efficacy in the treatment of HER2/neu amplified uterine serous carcinoma in vitro and in vivo. Gynecologic Oncology 2014, 135: 142-148. PMID: 25124161, DOI: 10.1016/j.ygyno.2014.08.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell CycleCell Line, TumorFemaleIn Vitro TechniquesMiceQuinolinesReceptor, ErbB-2Signal TransductionUterine NeoplasmsConceptsHER2/neu amplificationUterine serous carcinomaHER2/neuUSC cell linesNeu amplificationNon-amplified cell linesSerous carcinomaCell linesTyrosine kinase inhibitor neratinibEffects of neratinibPrimary USC cell linesEndometrial cancer patientsPotential treatment optionEfficacy of neratinibG0/G1 phaseCell cycle distributionActivation of S6Overall survivalEndometrial cancerAggressive variantTreatment optionsCancer patientsClinical trialsPrimary cell linesHER2 inhibitorsRegulation of tumor cell migration and invasion by the H19/let-7 axis is antagonized by metformin-induced DNA methylation
Yan L, Zhou J, Gao Y, Ghazal S, Lu L, Bellone S, Yang Y, Liu N, Zhao X, Santin AD, Taylor H, Huang Y. Regulation of tumor cell migration and invasion by the H19/let-7 axis is antagonized by metformin-induced DNA methylation. Oncogene 2014, 34: 3076-3084. PMID: 25088204, DOI: 10.1038/onc.2014.236.Peer-Reviewed Original ResearchConceptsTumor cell migrationDNA methylationCell migrationTumor suppressorH19/letPotent tumor suppressorExpression of oncogenesDiverse human cancersMetastasis-promoting genesAnti-diabetic drug metforminLet-7C-MycHuman cancersH19Cell growthNovel mechanismEndometrial cancerPoor prognosisRegulationDrug metforminMethylationTherapeutic opportunitiesSuppressorTumor cellsOncogene
2013
HER2 Expression Beyond Breast Cancer: Therapeutic Implications for Gynecologic Malignancies
English DP, Roque DM, Santin AD. HER2 Expression Beyond Breast Cancer: Therapeutic Implications for Gynecologic Malignancies. Molecular Diagnosis & Therapy 2013, 17: 85-99. PMID: 23529353, PMCID: PMC3660991, DOI: 10.1007/s40291-013-0024-9.Peer-Reviewed Original ResearchConceptsAggressive neoplasmCytotoxic chemotherapy agentsOverall poor survivalTyrosine kinase inhibitorsEpidermal growth factor (EGF) familyGrowth factor familyGynecologic malignanciesEndometrial cancerHER2 expressionClinical trialsOvarian cancerPoor survivalBreast cancerChemotherapy agentsC-erbB2 geneTherapeutic implicationsTumor typesHER2Monoclonal antibodiesSubset of breastKinase inhibitorsCancerNeoplasmsCell survivalBreastEarly stage uterine serous carcinoma: Management updates and genomic advances
Fader AN, Santin AD, Gehrig PA. Early stage uterine serous carcinoma: Management updates and genomic advances. Gynecologic Oncology 2013, 129: 244-250. PMID: 23321062, DOI: 10.1016/j.ygyno.2013.01.004.Peer-Reviewed Original ResearchConceptsEarly stage uterine serous carcinomaUterine serous carcinomaRisk of recurrenceResidual uterine diseaseTaxane-based chemotherapyEarly-stage diseaseNumber of patientsCancer-related deathHigh recurrence rateOptimal management approachHER2/neuPotential therapeutic targetAvailable literaturePIK3CA/Adjuvant therapyCervical involvementStage diseaseBiologic therapyProspective trialEndometrial cancerProspective studyRecurrence rateSerous carcinomaSurvival outcomesAggressive subtype
2009
In vitro activity of pertuzumab in combination with trastuzumab in uterine serous papillary adenocarcinoma
El-Sahwi K, Bellone S, Cocco E, Cargnelutti M, Casagrande F, Bellone M, Abu-Khalaf M, Buza N, Tavassoli FA, Hui P, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. In vitro activity of pertuzumab in combination with trastuzumab in uterine serous papillary adenocarcinoma. British Journal Of Cancer 2009, 102: 134-143. PMID: 19920829, PMCID: PMC2813756, DOI: 10.1038/sj.bjc.6605448.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma, PapillaryAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityCell Line, TumorComplement System ProteinsCytotoxicity, ImmunologicDimerizationDrug Screening Assays, AntitumorDrug SynergismFemaleHumansImmunoglobulin GIn Vitro TechniquesInterleukin-2Killer Cells, NaturalLymphocytesMiddle AgedReceptor, ErbB-2Signal TransductionTrastuzumabUterine NeoplasmsConceptsAntibody-dependent cell-mediated cytotoxicityUSPC cell linesHER2/neu expressionComplement-dependent cytotoxicityStrong antibody-dependent cell-mediated cytotoxicitySerous papillary adenocarcinomaNeu expressionHER2/neuPapillary adenocarcinomaHigh HER2/neu expressionLow HER2/neu expressionCell linesH chromium release assaysPrimary USPC cell linesAdvanced/recurrentCombination of pertuzumabCell-mediated cytotoxicityHumanised monoclonal antibodyChromium release assaysC-erbB2 gene amplificationActivity of pertuzumabNew therapeutic agentsProliferation-based assaysType II receptorEndometrial cancer
2008
A novel CD4 T-cell epitope described from one of the cervical cancer patients vaccinated with HPV 16 or 18 E7-pulsed dendritic cells
Wang X, Santin AD, Bellone S, Gupta S, Nakagawa M. A novel CD4 T-cell epitope described from one of the cervical cancer patients vaccinated with HPV 16 or 18 E7-pulsed dendritic cells. Cancer Immunology, Immunotherapy 2008, 58: 301-308. PMID: 18446336, PMCID: PMC2782377, DOI: 10.1007/s00262-008-0525-2.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigen PresentationCancer VaccinesCD4 AntigensDendritic CellsDose-Response Relationship, DrugEpitopes, T-LymphocyteFemaleHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHuman papillomavirus 16Human papillomavirus 18HumansMolecular Sequence DataNeoplasm StagingOncogene Proteins, ViralPapillomavirus E7 ProteinsSignal TransductionT-LymphocytesUterine Cervical NeoplasmsConceptsT cell epitopesCD4 T cell epitopesT cell responsesT cell clonesHPV 16T cell linesDose escalation phase I clinical trialPeripheral blood mononuclear cellsE7 proteinPositive T-cell responsesPhase I clinical trialAutologous mature DCDendritic cell vaccinationIIA cervical cancerCervical cancer patientsIFN-γ secretionBlood mononuclear cellsHuman papillomavirus type 16Papillomavirus type 16Cell vaccinationStage IBDendritic cellsMature DCsCervical cancerELISPOT assay