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 agentDual-Targeting Nanoparticles for In Vivo Delivery of Suicide Genes to Chemotherapy-Resistant Ovarian Cancer Cells
Cocco E, Deng Y, Shapiro EM, Bortolomai I, Lopez S, Lin K, Bellone S, Cui J, Menderes G, Black JD, Schwab CL, Bonazzoli E, Yang F, Predolini F, Zammataro L, Altwerger G, de Haydu C, Clark M, Alvarenga J, Ratner E, Azodi M, Silasi DA, Schwartz PE, Litkouhi B, Saltzman WM, Santin AD. Dual-Targeting Nanoparticles for In Vivo Delivery of Suicide Genes to Chemotherapy-Resistant Ovarian Cancer Cells. Molecular Cancer Therapeutics 2017, 16: 323-333. PMID: 27956521, PMCID: PMC5292071, DOI: 10.1158/1535-7163.mct-16-0501.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorCell SurvivalDisease Models, AnimalDrug CarriersDrug Delivery SystemsDrug Resistance, NeoplasmEnterotoxinsFemaleGene ExpressionGene Transfer TechniquesGenes, Transgenic, SuicideGenetic TherapyHumansMiceNanoparticlesOvarian NeoplasmsPromoter Regions, GeneticTumor BurdenXenograft Model Antitumor AssaysConceptsOvarian cancer cellsClostridium perfringens enterotoxinChemotherapy-resistant ovarian cancer cellsIntraperitoneal injectionCancer cellsMultiple intraperitoneal injectionsOvarian cancer xenograftsOvarian tumor cell linesLethal gynecologic cancerTumor-bearing miceOvarian cancer cell deathVivo biodistribution studiesGene therapySuicide gene therapyGynecologic cancerCancer xenograftsOvarian cancerCancer cell deathTherapeutic approachesControl nanoparticlesTumor growthTumor cell linesClaudin-3Biodistribution studiesTumor cells
2016
SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine Serous Carcinoma with HER2/Neu Expression
Black J, Menderes G, Bellone S, Schwab CL, Bonazzoli E, Ferrari F, Predolini F, De Haydu C, Cocco E, Buza N, Hui P, Wong S, Lopez S, Ratner E, Silasi DA, Azodi M, Litkouhi B, Schwartz PE, Goedings P, Beusker PH, van der Lee MM, Timmers CM, Dokter WH, Santin AD. SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine Serous Carcinoma with HER2/Neu Expression. Molecular Cancer Therapeutics 2016, 15: 1900-1909. PMID: 27256376, DOI: 10.1158/1535-7163.mct-16-0163.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsBystander EffectCathepsin BCell Line, TumorCell SurvivalClass I Phosphatidylinositol 3-KinasesCystadenocarcinoma, SerousDisease Models, AnimalDuocarmycinsFemaleGene ExpressionHumansImmunoconjugatesIndolesMiceMiddle AgedMutationPhosphatidylinositol 3-KinasesPyrrolidinonesReceptor, ErbB-2Survival AnalysisUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaAntibody-dependent cellular cytotoxicityHER2/neu expressionAntibody-drug conjugatesT-DM1Neu expressionHER2-targeting antibody-drug conjugateNovel antibody-drug conjugateNovel HER2-targeting antibody-drug conjugatePrimary USC cell linesHigh HER2 expressionHER2/neu oncogeneHER2/neuMouse xenograft modelUSC cell linesFlow cytometry assayEndometrial cancerSerous carcinomaHER2 expressionTrastuzumab emtansineClinical studiesCellular cytotoxicitySYD985Aggressive formExpress HER2
2014
T‐DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo
English DP, Bellone S, Schwab CL, Bortolomai I, Bonazzoli E, Cocco E, Buza N, Hui P, Lopez S, Ratner E, Silasi D, Azodi M, Schwartz PE, Rutherford TJ, Santin AD. T‐DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo. Cancer Medicine 2014, 3: 1256-1265. PMID: 24890382, PMCID: PMC4302675, DOI: 10.1002/cam4.274.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAgedAged, 80 and overAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsApoptosisCarcinomaCell Cycle CheckpointsCell ProliferationDisease Models, AnimalFemaleGene AmplificationGene ExpressionGene Expression Regulation, NeoplasticHumansImmunohistochemistryIn Situ Hybridization, FluorescenceMaytansineMiddle AgedReceptor, ErbB-2RNA, MessengerTrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaUSC cell linesNovel antibody-drug conjugateT-DM1USC xenograftsAntibody-drug conjugatesSerous carcinomaAntibody-dependent cell-mediated cytotoxicityEpidermal growth factor receptor 2Cell linesPrimary USC cell linesGrowth factor receptor 2Cell-mediated cytotoxicityChromium release assaysNovel treatment optionsHER2 protein overexpressionFactor receptor 2HER2 gene amplificationHER2 protein expressionC-erbB2 gene amplificationGene amplificationDisease refractoryPrimary HER2USC cellsUSC patients