2023
Uterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor
McNamara B, Harold J, Manavella D, Bellone S, Mutlu L, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Yang K, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Burton E, Inagaki H, Albers A, Zhang C, Bollag G, Schlessinger J, Santin A. Uterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor. Gynecologic Oncology 2023, 172: 65-71. PMID: 36958197, PMCID: PMC10192120, DOI: 10.1016/j.ygyno.2023.03.009.Peer-Reviewed Original ResearchConceptsUterine leiomyosarcomaPDX modelsGain of functionMedian overall survivalPhase I trialOral gavage dailyVivo activityTumor growth inhibitionTumor volume differencesTumor cell proliferationOverall survivalTolerable toxicityI trialOral treatmentTreatment cohortsGavage dailyAggressive tumorsSCID miceULMS patientsPK studiesTumor samplesWestern blotCell proliferationControl vehicleLeiomyosarcoma
2022
Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma
Harold J, Bellone S, Manavella D, Mutlu L, McNamara B, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Santin A. Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma. Gynecologic Oncology 2022, 168: 157-165. PMID: 36442427, PMCID: PMC9797429, DOI: 10.1016/j.ygyno.2022.11.014.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsUterine leiomyosarcomaVivo activityVehicle control treatmentMedian overall survivalTumor volume differencesOral scheduleWestern blot analysisOverall survivalOral gavageAggressive malignancyPDX modelsClinical trialsSCID miceTumor measurementsULMS patientsSignificant growth inhibitionNovel ATR inhibitorTumor samplesSignificant toxicityWestern blotKinase inhibitorsATRX mutationsGene mutationsControl vehicle
2020
Modeling biological and genetic diversity in upper tract urothelial carcinoma with patient derived xenografts
Kim K, Hu W, Audenet F, Almassi N, Hanrahan AJ, Murray K, Bagrodia A, Wong N, Clinton TN, Dason S, Mohan V, Jebiwott S, Nagar K, Gao J, Penson A, Hughes C, Gordon B, Chen Z, Dong Y, Watson PA, Alvim R, Elzein A, Gao SP, Cocco E, Santin AD, Ostrovnaya I, Hsieh JJ, Sagi I, Pietzak EJ, Hakimi AA, Rosenberg JE, Iyer G, Vargas HA, Scaltriti M, Al-Ahmadie H, Solit DB, Coleman JA. Modeling biological and genetic diversity in upper tract urothelial carcinoma with patient derived xenografts. Nature Communications 2020, 11: 1975. PMID: 32332851, PMCID: PMC7181640, DOI: 10.1038/s41467-020-15885-7.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBiopsyCamptothecinCarcinoma, Transitional CellFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenetic VariationHigh-Throughput Nucleotide SequencingHumansImmunoconjugatesInterleukin Receptor Common gamma SubunitMaleMiceMice, Inbred NODMice, SCIDMiddle AgedMutationNeoplasm MetastasisNeoplasm TransplantationPhenotypePrecision MedicineProspective StudiesQuinolinesRetrospective StudiesSequence Analysis, RNATrastuzumabUrinary Bladder NeoplasmsUrotheliumConceptsUpper tract urothelial carcinomaUrothelial carcinomaCorresponding patient tumorsEstablishment of patientHigh genomic concordancePersonalized medicine strategiesHER2 kinase inhibitorDisease-specific modelsUTUC patientsCell line modelsPDX modelsBladder cancerTreatment paradigmGenomic concordanceInvasive tumorsSuperior efficacyPatient tumorsPatientsKinase inhibitorsAntibody drugsMedicine strategiesBiological heterogeneityCarcinomaXenograftsTumorsSacituzumab govitecan, an antibody‐drug conjugate targeting trophoblast cell‐surface antigen 2, shows cytotoxic activity against poorly differentiated endometrial adenocarcinomas in vitro and in vivo
Perrone E, Manara P, Lopez S, Bellone S, Bonazzoli E, Manzano A, Zammataro L, Bianchi A, Zeybek B, Buza N, Tymon‐Rosario J, Altwerger G, Han C, Menderes G, Huang GS, Ratner E, Silasi D, Azodi M, Hui P, Schwartz PE, Scambia G, Santin AD. Sacituzumab govitecan, an antibody‐drug conjugate targeting trophoblast cell‐surface antigen 2, shows cytotoxic activity against poorly differentiated endometrial adenocarcinomas in vitro and in vivo. Molecular Oncology 2020, 14: 645-656. PMID: 31891442, PMCID: PMC7053235, DOI: 10.1002/1878-0261.12627.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmAntineoplastic AgentsCamptothecinCarcinoma, EndometrioidCell Adhesion MoleculesCell DifferentiationCell Line, TumorCell SurvivalEndometrial NeoplasmsFemaleHumansImmunoconjugatesImmunohistochemistryIrinotecanMiceMice, SCIDTissue Array AnalysisXenograft Model Antitumor AssaysConceptsAntibody-dependent cell cytotoxicityCell surface antigen 2EC cell linesSacituzumab govitecanTrop-2 expressionPrimary tumor cell linesTrop-2Xenograft modelAntigen 2Cell linesTumor cell linesCommon gynecologic malignancyFuture clinical trialsChromium release assaysParaffin-embedded tumorsTumor growth inhibitionSignificant bystander killingEC xenograftsGynecologic malignanciesEndometrial cancerEndometrial adenocarcinomaEndometrioid carcinoma tissuesPreclinical activityControl antibodyClinical trials
2019
In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma
Han C, Perrone E, Zeybek B, Bellone S, Tymon-Rosario J, Altwerger G, Menderes G, Feinberg J, Haines K, Muller Karger ME, Bianchi A, Zammataro L, Manzano A, Bonazzoli E, Manara P, Buza N, Hui P, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Lopez S, Santin AD. In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma. Gynecologic Oncology 2019, 156: 430-438. PMID: 31839338, DOI: 10.1016/j.ygyno.2019.11.018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmCamptothecinCell Adhesion MoleculesCell Line, TumorCystadenocarcinoma, SerousFemaleFlow CytometryHumansImmunoconjugatesImmunohistochemistryMiceMice, SCIDMolecular Targeted TherapyRandom AllocationTissue Array AnalysisUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaCell surface antigen 2Sacituzumab govitecanTrop-2 expressionTrop-2Serous carcinomaAntigen 2Advanced/recurrent diseasePrimary uterine serous carcinomaResistant human tumorsSignificant bystander killingUSC patientsUSC xenograftsRecurrent diseaseClinical responseEndometrial cancerAggressive variantPoor prognosisPreclinical activityPrimary tumorIntravenous administrationClinical developmentUSC samplesActive metaboliteSN-38PARP-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 activityPI3K oncogenic mutations mediate resistance to afatinib in HER2/neu overexpressing gynecological cancers
Bonazzoli E, Cocco E, Lopez S, Bellone S, Zammataro L, Bianchi A, Manzano A, Yadav G, Manara P, Perrone E, Haines K, Espinal M, Dugan K, Menderes G, Altwerger G, Han C, Zeybek B, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. PI3K oncogenic mutations mediate resistance to afatinib in HER2/neu overexpressing gynecological cancers. Gynecologic Oncology 2019, 153: 158-164. PMID: 30630630, PMCID: PMC6430698, DOI: 10.1016/j.ygyno.2019.01.002.Peer-Reviewed Original ResearchMeSH KeywordsAdultAfatinibAgedAnimalsAntineoplastic AgentsCell Line, TumorClass I Phosphatidylinositol 3-KinasesClass Ia Phosphatidylinositol 3-KinaseDrug Resistance, NeoplasmFemaleGenital Neoplasms, FemaleHumansMiceMice, SCIDMiddle AgedMutationPhosphatidylinositol 3-KinasesProtein Kinase InhibitorsReceptor, ErbB-2TransfectionXenograft Model Antitumor AssaysConceptsHER2/neuAKT/mTOR pathwayPIK3CA mutationsMTOR pathwayActivity of afatinibEffect of afatinibPI3K/AKT/mTOR pathwayPotential mechanismsPIK3CA/AKT/mTOR pathwayRapid tumor growthGreater compensatory increasePI3K mutationsAmplification/mutationOncogenic PIK3CA mutationsAfatinib exposurePIK3CA H1047RGynecological cancerClinical trialsMTOR inhibitorsAfatinibTumor growthCompensatory increasePhosphorylated Akt proteinPIK3CA geneC-erb
2018
In vitro and in vivo activity of IMGN853, an Antibody-Drug Conjugate targeting Folate Receptor Alpha linked to DM4, in biologically aggressive endometrial cancers
Altwerger G, Bonazzoli E, Bellone S, Egawa-Takata T, Menderes G, Pettinella F, Bianchi A, Riccio F, Feinberg J, Zammataro L, Han C, Yadav G, Dugan K, Morneault A, Ponte JF, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. In vitro and in vivo activity of IMGN853, an Antibody-Drug Conjugate targeting Folate Receptor Alpha linked to DM4, in biologically aggressive endometrial cancers. Molecular Cancer Therapeutics 2018, 17: molcanther.0930.2017. PMID: 29440294, PMCID: PMC5932245, DOI: 10.1158/1535-7163.mct-17-0930.Peer-Reviewed Original ResearchConceptsEndometrial cancerXenograft modelCell linesTumor cell linesPatient-derived xenograft modelsUterine cancer cell linesAggressive endometrial cancersEndometrial cancer deathsExpression of FRαPrimary USC cell linesRecurrent endometrial cancerReceptor alpha expressionUSC cell linesImpressive antitumor activityMol Cancer TherUSC patientsCancer cell linesMedian survivalCancer deathPDX modelsPreclinical dataUterine cancerComplete resolutionIMGN853Grade 3
2017
Superior in vitro and in vivo activity of trastuzumab-emtansine (T-DM1) in comparison to trastuzumab, pertuzumab and their combination in epithelial ovarian carcinoma with high HER2/neu expression
Menderes G, Bonazzoli E, Bellone S, Altwerger G, Black JD, Dugan K, Pettinella F, Masserdotti A, Riccio F, Bianchi A, Zammataro L, de Haydu C, Buza N, Hui P, Wong S, Huang GS, Litkouhi B, Ratner E, Silasi DA, Azodi M, Schwartz PE, Santin AD. Superior in vitro and in vivo activity of trastuzumab-emtansine (T-DM1) in comparison to trastuzumab, pertuzumab and their combination in epithelial ovarian carcinoma with high HER2/neu expression. Gynecologic Oncology 2017, 147: 145-152. PMID: 28705408, PMCID: PMC5605415, DOI: 10.1016/j.ygyno.2017.07.009.Peer-Reviewed Original ResearchConceptsHigh HER2/neu expressionHER2/neu expressionEpithelial ovarian cancerHER2/neuAnti-tumor activityEOC cell linesT-DM1Neu expressionChemotherapy-resistant epithelial ovarian cancerLimited anti-tumor activityAntibody-dependent cell-mediated cytotoxicity (ADCC) activityCell linesSuperior anti-tumor activityCombination of trastuzumabLethal gynecologic malignancyEpithelial ovarian carcinomaTumor growth inhibitionEOC xenograftsGynecologic malignanciesPreclinical dataOvarian carcinomaOvarian cancerClinical studiesXenograft modelSingle agentSYD985, a novel duocarmycin-based HER2-targeting antibody-drug conjugate, shows promising antitumor activity in epithelial ovarian carcinoma with HER2/Neu expression
Menderes G, Bonazzoli E, Bellone S, Black J, Altwerger G, Masserdotti A, Pettinella F, Zammataro L, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. SYD985, a novel duocarmycin-based HER2-targeting antibody-drug conjugate, shows promising antitumor activity in epithelial ovarian carcinoma with HER2/Neu expression. Gynecologic Oncology 2017, 146: 179-186. PMID: 28473206, PMCID: PMC5533304, DOI: 10.1016/j.ygyno.2017.04.023.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntineoplastic Agents, AlkylatingBystander EffectCarcinoma, Ovarian EpithelialCell Line, TumorDuocarmycinsFemaleHumansImmunotoxinsIndolesMaytansineMiceMice, SCIDMiddle AgedNeoplasms, Glandular and EpithelialOvarian NeoplasmsPyrrolidinonesRandom AllocationReceptor, ErbB-2TrastuzumabXenograft Model Antitumor AssaysConceptsHER2/neu expressionAntibody-dependent cellular cytotoxicityEpithelial ovarian cancerLow HER2/neu expressionPeripheral blood lymphocytesHER2/neu 3Antibody-drug conjugatesT-DM1Neu expressionEOC cell linesNeu 3HER2-targeting antibody-drug conjugateNovel antibody-drug conjugateNovel HER2-targeting antibody-drug conjugateEpithelial ovarian carcinomaOvarian cancer xenograftsAnti-tumor activityCell linesEOC xenograftsTrastuzumab emtansineCancer xenograftsBlood lymphocytesOvarian cancerOvarian carcinomaSYD985
2015
Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo
Lopez S, Cocco E, Black J, Bellone S, Bonazzoli E, Predolini F, Ferrari F, Schwab CL, English DP, Ratner E, Silasi DA, Azodi M, Schwartz PE, Terranova C, Angioli R, Santin AD. Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo. Molecular Cancer Therapeutics 2015, 14: 2519-2526. PMID: 26333383, PMCID: PMC4636465, DOI: 10.1158/1535-7163.mct-15-0383.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsCell CycleCell Line, TumorCell SurvivalClass I Phosphatidylinositol 3-KinasesCystadenocarcinoma, SerousDose-Response Relationship, DrugDrug SynergismFemaleGene AmplificationHumansImidazolesImmunoblottingMice, SCIDMutationOxazepinesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationQuinolinesReceptor, ErbB-2Uterine NeoplasmsXenograft Model Antitumor AssaysConceptsHER2/neu gene amplificationNeu gene amplificationUSC xenograftsUterine serous carcinomaGene amplificationUterine serous carcinoma cell linesSingle-agent therapyNovel therapeutic optionsWild-type PIK3CADose-dependent increaseIdeal therapeutic targetUSC cell linesCell linesDose-dependent declineFlow cytometry assayG0-G1 phaseCell cycle distributionOncogenic PIK3CA mutationsPercentage of cellsUSC patientsEndometrial cancerAggressive variantSerous carcinomaTherapeutic optionsCarcinoma cell linesEvaluation of a novel human IgG1 anti-claudin3 antibody that specifically recognizes its aberrantly localized antigen in ovarian cancer cells and that is suitable for selective drug delivery
Romani C, Cocco E, Bignotti E, Moratto D, Bugatti A, Todeschini P, Bandiera E, Tassi R, Zanotti L, Pecorelli S, Sartori E, Odicino FE, de Marco A, Santin AD, Ravaggi A, Mitola S. Evaluation of a novel human IgG1 anti-claudin3 antibody that specifically recognizes its aberrantly localized antigen in ovarian cancer cells and that is suitable for selective drug delivery. Oncotarget 2015, 6: 34617-34628. PMID: 26416446, PMCID: PMC4741477, DOI: 10.18632/oncotarget.5315.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeoplasmAntibody AffinityAntineoplastic AgentsBlotting, WesternCell Line, TumorClaudin-3Drug CarriersDrug Delivery SystemsEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryHumansImmunoglobulin GMiceMice, SCIDMicroscopy, ConfocalMicroscopy, FluorescenceOvarian NeoplasmsReal-Time Polymerase Chain ReactionRNA, Small InterferingSurface Plasmon ResonanceTransfectionXenograft Model Antitumor AssaysConceptsClostridium perfringens enterotoxinTumor cellsActive anti-cancer compoundsHuman IgG1 Fc domainHuman ovarian cancer cell linesOvarian cancer cell linesOvarian cancer patientsOvarian carcinoma xenograftsOvarian cancer cellsIgG1 Fc domainCancer cell linesAggressive tumorsCancer patientsCarcinoma xenograftsOncological settingIgG1 antibodiesClaudin3Anti-cancer compoundsChimeric antibodyAntitumor efficacySelective drug deliveryPerfringens enterotoxinCancer cellsAntibodiesFc domainClostridium perfringens enterotoxin C‐terminal domain labeled to fluorescent dyes for in vivo visualization of micrometastatic chemotherapy‐resistant ovarian cancer
Cocco E, Shapiro EM, Gasparrini S, Lopez S, Schwab CL, Bellone S, Bortolomai I, Sumi NJ, Bonazzoli E, Nicoletti R, Deng Y, Saltzman WM, Zeiss CJ, Centritto F, Black JD, Silasi DA, Ratner E, Azodi M, Rutherford TJ, Schwartz PE, Pecorelli S, Santin AD. Clostridium perfringens enterotoxin C‐terminal domain labeled to fluorescent dyes for in vivo visualization of micrometastatic chemotherapy‐resistant ovarian cancer. International Journal Of Cancer 2015, 137: 2618-2629. PMID: 26060989, PMCID: PMC4573336, DOI: 10.1002/ijc.29632.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsTumor fluorescenceChemotherapy-resistant ovarian cancerClaudin-3Human ovarian cancer xenograftsTime of surgeryOvarian cancer patientsNeoadjuvant chemotherapy treatmentOvarian cancer xenograftsHealthy organsVivo visualizationTime of intervalBackground fluorescence ratioClostridium perfringens enterotoxinChemotherapy-naïveMicrometastatic diseaseMalignant ascitesOvarian diseaseResidual diseaseOvarian tumorsCancer patientsCancer xenograftsChemotherapy treatmentIP injectionOvarian cancerNeratinib shows efficacy in the treatment of HER2 amplified carcinosarcoma in vitro and in vivo
Schwab CL, English DP, Black J, Bellone S, Lopez S, Cocco E, Bonazzoli E, Bussi B, Predolini F, Ferrari F, Ratner E, Silasi DA, Azodi M, Rutherford T, Schwartz PE, Santin AD. Neratinib shows efficacy in the treatment of HER2 amplified carcinosarcoma in vitro and in vivo. Gynecologic Oncology 2015, 139: 112-117. PMID: 26260909, PMCID: PMC4587290, DOI: 10.1016/j.ygyno.2015.08.002.Peer-Reviewed Original ResearchConceptsHER2/neuTreatment of HER2Efficacy of neratinibCarcinosarcoma cell lineTumor growthCell linesEffective treatment optionDeadliest gynecologic malignancyG0/G1 phaseCell cycle distributionCell signaling changesActivation of S6Neratinib treatmentGynecologic malignanciesOverall survivalTreatment optionsClinical trialsXenograft growthNew therapiesHER2NeratinibFlow cytometryNeuCycle distributionSignaling changes
2014
T-DM1, a novel antibody-drug conjugate, is highly effective against uterine and ovarian carcinosarcomas overexpressing HER2
Nicoletti R, Lopez S, Bellone S, Cocco E, Schwab CL, Black JD, Centritto F, Zhu L, Bonazzoli E, Buza N, Hui P, Mezzanzanica D, Canevari S, Schwartz PE, Rutherford TJ, Santin AD. T-DM1, a novel antibody-drug conjugate, is highly effective against uterine and ovarian carcinosarcomas overexpressing HER2. Clinical & Experimental Metastasis 2014, 32: 29-38. PMID: 25398397, PMCID: PMC4310789, DOI: 10.1007/s10585-014-9688-8.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsCarcinosarcomaCell Line, TumorCell ProliferationFemaleImmunoconjugatesM Phase Cell Cycle CheckpointsMaytansineMiceMice, SCIDOvarian NeoplasmsReceptor, ErbB-2TrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsCS cell linesT-DM1Cell linesFlow cytometryNovel antibody-drug conjugateAggressive clinical behaviorNovel treatment optionsG2/M phase cell cycle arrestHER2 protein overexpressionM phase cell cycle arrestPhase cell cycle arrestAntibody-drug conjugatesDisease refractoryPrimary HER2Vehicle miceOvarian carcinosarcomaPoor prognosisUterine carcinosarcomaCS patientsTreatment optionsClinical behaviorLonger survivalCell cycle arrestHER2 amplificationCarcinosarcomaAfatinib 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 xenografts
2011
Eradication of chemotherapy‐resistant CD44+ human ovarian cancer stem cells in mice by intraperitoneal administration of clostridium perfringens enterotoxin
Casagrande F, Cocco E, Bellone S, Richter CE, Bellone M, Todeschini P, Siegel E, Varughese J, Arin‐Silasi D, Azodi M, Rutherford TJ, Pecorelli S, Schwartz PE, Santin AD. Eradication of chemotherapy‐resistant CD44+ human ovarian cancer stem cells in mice by intraperitoneal administration of clostridium perfringens enterotoxin. Cancer 2011, 117: 5519-5528. PMID: 21692061, PMCID: PMC3701957, DOI: 10.1002/cncr.26215.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsCarcinoma, Ovarian EpithelialCell Line, TumorChlorocebus aethiopsClaudin-3ClaudinsClostridium perfringensEnterotoxinsFemaleFlow CytometryHumansHyaluronan ReceptorsInjections, IntraperitonealMiceMice, SCIDMiddle AgedNeoplasms, Glandular and EpithelialNeoplastic Stem CellsOvarian NeoplasmsReal-Time Polymerase Chain ReactionVero CellsXenograft Model Antitumor AssaysConceptsOvarian cancer stem cellsCancer stem cellsClostridium perfringens enterotoxinCPE-induced cytotoxicityIntraperitoneal administrationStem cellsC.B-17/SCID miceChemotherapy-resistant cancer stem cellsHuman ovarian cancer stem cellsPerfringens enterotoxinClaudin-4 genesStem cell linesLong-term survivalOvarian cancer cellsReal-time polymerase chain reactionTight junction proteinsHigh-affinity receptorMultiple intraperitoneal administrationCancer stem cell linesPolymerase chain reactionSmall-interfering RNACell xenograftsSCID miceSignificant inhibitory effectChemotherapy resistance
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
2007
Overexpression of Clostridium perfringens Enterotoxin Receptors Claudin-3 and Claudin-4 in Uterine Carcinosarcomas
Santin AD, Bellone S, Siegel ER, McKenney JK, Thomas M, Roman JJ, Burnett A, Tognon G, Bandiera E, Pecorelli S. Overexpression of Clostridium perfringens Enterotoxin Receptors Claudin-3 and Claudin-4 in Uterine Carcinosarcomas. Clinical Cancer Research 2007, 13: 3339-3346. PMID: 17545541, DOI: 10.1158/1078-0432.ccr-06-3037.Peer-Reviewed Original ResearchConceptsCarcinosarcoma cell lineClaudin-3Claudin-4Uterine carcinosarcomaClaudin-4 protein expressionCell linesClaudin-4 receptorsCytotoxic Clostridium perfringensNormal endometrial cellsTumor cell necrosisType-specific therapiesImmunodeficient mouse xenograftsAggressive uterine tumorsHigh-affinity receptorQuantitative reverse transcription PCREndometrial cancerAggressive variantUterine tumorsTumor disappearancePrimary tumorReverse transcription-PCREndometrial cellsNovel therapiesReceptor expressionTherapeutic effectOverexpression of claudin‐3 and claudin‐4 receptors in uterine serous papillary carcinoma
Santin AD, Bellone S, Marizzoni M, Palmieri M, Siegel ER, McKenney JK, Hennings L, Comper F, Bandiera E, Pecorelli S. Overexpression of claudin‐3 and claudin‐4 receptors in uterine serous papillary carcinoma. Cancer 2007, 109: 1312-1322. PMID: 17326053, DOI: 10.1002/cncr.22536.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsClaudin-3Claudin-4Clostridium perfringensCystadenocarcinoma, PapillaryCystadenocarcinoma, SerousDrug Resistance, NeoplasmEnterotoxinsFemaleGene ExpressionHumansInjections, IntraperitonealMembrane ProteinsMiceMice, SCIDMiddle AgedReverse Transcriptase Polymerase Chain ReactionRNA, MessengerTumor Cells, CulturedUp-RegulationUterine Cervical NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous papillary carcinomaClaudin-4 receptorsUSPC cell linesSerous papillary carcinomaClaudin-3Endometrial cancerPapillary carcinomaClaudin-4 protein expressionChemotherapy-resistant variantsCytotoxic Clostridium perfringensSublethal intraperitoneal injectionsReverse transcriptase-polymerase chain reactionQuantitative reverse transcriptase-polymerase chain reactionTumor cell necrosisSCID mouse xenograftsType-specific therapiesDose-dependent cytotoxic effectCell linesTight junction proteinsControl tissue samplesHigh-affinity receptorAggressive variantTumor disappearanceIntraperitoneal injectionPolymerase chain reaction