2022
Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer
Makker V, Colombo N, Casado Herráez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. New England Journal Of Medicine 2022, 386: 437-448. PMID: 35045221, DOI: 10.1056/nejmoa2108330.Peer-Reviewed Original ResearchConceptsAdvanced endometrial cancerProgression-free survivalEndometrial cancerOverall survivalMedian progression-free survivalPlatinum-based chemotherapy regimenLonger progression-free survivalEnd pointBlinded independent central reviewMedian overall survivalPrimary end pointPhase 3 trialResponse Evaluation CriteriaPlatinum-based chemotherapyIndependent central reviewChemotherapy regimenAdverse eventsStandard therapyCentral reviewPembrolizumabGrade 3LenvatinibChemotherapyPhysician's choicePatients
2021
DHES0815A, a novel antibody-drug conjugate targeting HER2/neu, is highly active against uterine serous carcinomas in vitro and in vivo
Tymon-Rosario J, Bonazzoli E, Bellone S, Manzano A, Pelligra S, Guglielmi A, Gnutti B, Nagarkatti N, Zeybek B, Manara P, Zammataro L, Harold J, Mauricio D, Buza N, Hui P, Altwerger G, Menderes G, Ratner E, Clark M, Andikyan V, Huang GS, Silasi DA, Azodi M, Schwartz PE, Santin AD. DHES0815A, a novel antibody-drug conjugate targeting HER2/neu, is highly active against uterine serous carcinomas in vitro and in vivo. Gynecologic Oncology 2021, 163: 334-341. PMID: 34452746, PMCID: PMC8722447, DOI: 10.1016/j.ygyno.2021.08.014.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedBenzodiazepinesBystander EffectCell Line, TumorCystadenocarcinoma, SerousDrug Resistance, NeoplasmFemaleHumansImmunoconjugatesMiddle AgedPrimary Cell CultureReceptor, ErbB-2TrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsHER2/neuPrimary USC cell linesUSC cell linesUterine serous carcinomaSerous carcinomaHER2/Cell linesBystander killingHER2/neu protein expressionHER2/neu overexpressionProtein expressionNovel treatment optionsAggressive histologic variantNeu protein expressionHER2 protein expressionC-erbB2 gene amplificationSignificant bystander killingUSC xenograftsEndometrial cancerNegative tumorsPoor prognosisPositive tumorsTreatment optionsPreclinical activityHistologic variants
2020
Stage III uterine serous carcinoma: modern trends in multimodality treatment
Li JY, Young MR, Huang G, Litkouhi B, Santin A, Schwartz PE, Damast S. Stage III uterine serous carcinoma: modern trends in multimodality treatment. Journal Of Gynecologic Oncology 2020, 31: e53. PMID: 32266802, PMCID: PMC7286763, DOI: 10.3802/jgo.2020.31.e53.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaExternal beam RTVaginal brachytherapyOverall survivalHuman epidermal growth factor receptorModern treatment eraSentinel node samplingRegional nodal recurrenceKaplan-Meier estimatesLog-rank testCox proportional hazardsExternal beam radiotherapyEpidermal growth factor receptorERA treatmentGrowth factor receptorUSC patientsFree survivalNodal recurrenceTreatment eraMultimodality treatmentPatient characteristicsPerioperative periodRegional nodalSerous carcinomaNode sampling
2019
HER2 testing of gynecologic carcinosarcomas: tumor stratification for potential targeted therapy
Rottmann D, Snir OL, Wu X, Wong S, Hui P, Santin AD, Buza N. HER2 testing of gynecologic carcinosarcomas: tumor stratification for potential targeted therapy. Modern Pathology 2019, 33: 118-127. PMID: 31477811, DOI: 10.1038/s41379-019-0358-x.Peer-Reviewed Original ResearchConceptsEndometrial serous carcinomaHER2-positive tumorsSerous carcinomaSarcoma componentHER2 statusGynecologic carcinosarcomaHER2 expression/amplificationRecent phase II clinical trialPhase II clinical trialCarboplatin-paclitaxel chemotherapyEquivocal HER2 expressionProgression-free survivalAppropriate patient selectionExpression/amplificationFemale genital tractMembranous staining patternHER2 protein expressionHER2 immunohistochemical scoresUterine primaryDismal prognosisPatient selectionCarcinoma componentMixed carcinomasHER2 expressionClinical trialsSacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer
Bardia A, Mayer IA, Vahdat LT, Tolaney SM, Isakoff SJ, Diamond JR, O'Shaughnessy J, Moroose RL, Santin AD, Abramson VG, Shah NC, Rugo HS, Goldenberg DM, Sweidan AM, Iannone R, Washkowitz S, Sharkey RM, Wegener WA, Kalinsky K. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. New England Journal Of Medicine 2019, 380: 741-751. PMID: 30786188, DOI: 10.1056/nejmoa1814213.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnemiaAntibodies, Monoclonal, HumanizedAntigens, NeoplasmAntineoplastic AgentsCamptothecinCell Adhesion MoleculesDiarrheaDose-Response Relationship, DrugFemaleHumansImmunoconjugatesInfusions, IntravenousIrinotecanMaleMiddle AgedNeutropeniaProgression-Free SurvivalSurvival RateTriple Negative Breast NeoplasmsConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerSacituzumab govitecan-hziyProgression-free survivalClinical benefit rateIndependent central reviewBreast cancerResponse rateAdverse eventsOverall survivalCentral reviewBenefit rateHuman trophoblast cell surface antigen 2Refractory metastatic triple-negative breast cancerTrophoblast cell surface antigen 2Median progression-free survivalSN-38Shorter progression-free survivalCell surface antigen 2Blinded independent central reviewDurable objective responsesPrevious anticancer therapyUnacceptable toxic effectsObjective response rateMain adverse reactions
2018
Inhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer
Bonazzoli E, Predolini F, Cocco E, Bellone S, Altwerger G, Menderes G, Zammataro L, Bianchi A, Pettinella F, Riccio F, Han C, Yadav G, Lopez S, Manzano A, Manara P, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Schlessinger J, Santin AD. Inhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer. Clinical Cancer Research 2018, 24: 4845-4853. PMID: 29941483, PMCID: PMC6168417, DOI: 10.1158/1078-0432.ccr-18-0864.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntineoplastic AgentsApoptosisAurora Kinase AAurora Kinase BAzepinesCell Line, TumorCell ProliferationCystadenocarcinoma, SerousDose-Response Relationship, DrugEndometrial NeoplasmsExome SequencingFemaleGene Expression Regulation, NeoplasticHumansMiceMiddle AgedPhosphorylationPrimary Cell CultureProteinsProto-Oncogene Proteins c-mycTriazolesUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaPrimary USC cell linesUSC cell linesC-myc expressionCell linesC-MycChemotherapy-resistant diseaseQRT-PCRHigh c-myc expressionDose-dependent decreaseDose-dependent increasePotential therapeutic targetEffective therapeutic agentMouse xenograft modelClin Cancer ResFresh frozen tumor tissueC-myc gene amplificationUSC xenograftsEndometrial cancerAggressive variantSerous carcinomaWhole-exome sequencing studiesClinical studiesConcentrations/dosesXenograft modelImpact of carboplatin hypersensitivity and desensitization on patients with recurrent ovarian cancer
Altwerger G, Florsheim EB, Menderes G, Black J, Schwab C, Gressel GM, Nelson WK, Carusillo N, Passante T, Huang G, Litkouhi B, Azodi M, Silasi DA, Santin A, Schwartz PE, Ratner ES. Impact of carboplatin hypersensitivity and desensitization on patients with recurrent ovarian cancer. Journal Of Cancer Research And Clinical Oncology 2018, 144: 2449-2456. PMID: 30255380, DOI: 10.1007/s00432-018-2753-y.Peer-Reviewed Original ResearchConceptsCarboplatin hypersensitivityCarboplatin desensitizationHypersensitive patientsOverall survivalRisk factorsOvarian cancerTwo-sided Fisher exactAdvanced stage ovarian cancerInfusion of carboplatinRecurrent ovarian cancerIndependent risk factorLonger overall survivalStage ovarian cancerOvarian cancer patientsLong-term treatmentNew risk factorsHigher likelihoodTwo-sided p valueT-testStudent's t-testDesignRetrospective studyGermline BRCA1/2Improved OSLonger OSDesensitization protocolExceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement
Bellone S, Buza N, Choi J, Zammataro L, Gay L, Elvin J, Rimm DL, Liu Y, Ratner E, Schwartz PE, Santin AD. Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement. Clinical Cancer Research 2018, 24: 3282-3291. PMID: 29351920, PMCID: PMC6050068, DOI: 10.1158/1078-0432.ccr-17-1805.Peer-Reviewed Original ResearchMeSH KeywordsAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyComputational BiologyDrug Resistance, NeoplasmExome SequencingFemaleGene RearrangementHLA AntigensHumansMolecular Targeted TherapyMutationOvarian NeoplasmsPositron Emission Tomography Computed TomographyProgrammed Cell Death 1 ReceptorReceptors, Cell SurfaceRetreatmentT-LymphocytesTreatment OutcomeConceptsImmune checkpoint inhibitor pembrolizumabCheckpoint inhibitor pembrolizumabComplete clinical responseClinical responsePD-L1Ovarian carcinomaAberrant PD-L1 expressionPD-L1 surface expressionAnti-PD1 inhibitorsPD-L1 expressionRemarkable clinical responsesHigh-grade ovarian carcinomaStandard treatment modalityAlternative therapeutic optionClear cell featuresNovel treatment optionsSignificant side effectsT-cell lymphocytesWhole exome sequencing techniqueClin Cancer ResMetastatic human tumorsRecurrent diseaseComplete responseHeavy infiltrationTherapeutic optionsRandomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu.
Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers SK, Secord AA, Havrilesky L, O'Malley DM, Backes F, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi KS, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu. Journal Of Clinical Oncology 2018, 36: 2044-2051. PMID: 29584549, DOI: 10.1200/jco.2017.76.5966.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2Progression-free survivalUterine serous carcinomaRecurrent uterine serous carcinomaMedian progression-free survivalRandomized phase II trialEpidermal growth factor receptor 2Phase II trialGrowth factor receptor 2Serous carcinomaHER2/neuFactor receptor 2II trialTreatment armsReceptor 2Stage IIIHER2/neu-positive diseaseOne-sided log-rank testMethods Eligible patientsPrimary end pointPrimary stage IIIUnexpected safety signalsLog-rank testHumanized monoclonal antibodyEligible patientsMicroRNA signatures discriminate between uterine and ovarian serous carcinomas
Hui P, Gysler SM, Uduman M, Togun TA, Prado DE, Brambs CE, Nallur S, Schwartz PE, Rutherford TJ, Santin AD, Weidhaas JB, Ratner ES. MicroRNA signatures discriminate between uterine and ovarian serous carcinomas. Human Pathology 2018, 76: 133-140. PMID: 29518404, DOI: 10.1016/j.humpath.2018.02.019.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorCarcinomaDiagnosis, DifferentialFemaleGene Expression ProfilingGenetic Predisposition to DiseaseHumansMicroRNAsMiddle AgedNeoplasm GradingNeoplasms, Cystic, Mucinous, and SerousOligonucleotide Array Sequence AnalysisOvarian NeoplasmsPhenotypePredictive Value of TestsReproducibility of ResultsRetrospective StudiesTranscriptomeUterine NeoplasmsConceptsHigh-grade serous carcinomaOvarian serous carcinomaSerous carcinomaOvarian malignancyPrimary ovarian high-grade serous carcinomaOvarian high-grade serous carcinomaMiRNA signatureEndometrial serous carcinomaHigh-grade ovarian serous carcinomaUterine serous carcinomaEndometrial counterpartOvarian primaryTaqMan Low Density Array technologySynchronous primariesEndometrial cancerMetastatic tumorsCarcinomaPrimary siteSignature panelPathological determinationMicroRNA signatureSignificant discriminatory powerCancer cellsMalignancyLineage characteristics
2017
FOXM1 expression is significantly associated with chemotherapy resistance and adverse prognosis in non-serous epithelial ovarian cancer patients
Tassi RA, Todeschini P, Siegel ER, Calza S, Cappella P, Ardighieri L, Cadei M, Bugatti M, Romani C, Bandiera E, Zanotti L, Tassone L, Guarino D, Santonocito C, Capoluongo ED, Beltrame L, Erba E, Marchini S, D’Incalci M, Donzelli C, Santin AD, Pecorelli S, Sartori E, Bignotti E, Odicino F, Ravaggi A. FOXM1 expression is significantly associated with chemotherapy resistance and adverse prognosis in non-serous epithelial ovarian cancer patients. Journal Of Experimental & Clinical Cancer Research 2017, 36: 63. PMID: 28482906, PMCID: PMC5422964, DOI: 10.1186/s13046-017-0536-y.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarcinoma, Ovarian EpithelialCell Line, TumorCell MovementCell ProliferationCell Transformation, NeoplasticCystadenocarcinoma, SerousDisease ProgressionDNA RepairDrug Resistance, NeoplasmFemaleForkhead Box Protein M1Gene Expression ProfilingGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansKaplan-Meier EstimateMiddle AgedNeoplasm GradingNeoplasm MetastasisNeoplasm StagingNeoplasms, Glandular and EpithelialOvarian NeoplasmsPrognosisProtein IsoformsRNA, Small InterferingConceptsForkhead box M1FOXM1 expressionEOC cell linesSerous EOCNormal controlsEOC subtypesCox proportional hazards analysisWorse disease-specific survivalEpithelial ovarian cancer patientsCell linesPlatinum-resistant casesSnap-frozen biopsiesDisease-specific survivalPlatinum-resistant diseaseAdvanced FIGO stageProportional hazards analysisProtein overexpressionClinic-pathological parametersOvarian cancer patientsRT-qPCRTransient siRNA transfectionPARP inhibitor olaparibFIGO stageSerous histologySpecific survival
2016
Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro
Bellone S, Bignotti E, Lonardi S, Ferrari F, Centritto F, Masserdotti A, Pettinella F, Black J, Menderes G, Altwerger G, Hui P, Lopez S, de Haydu C, Bonazzoli E, Predolini F, Zammataro L, Cocco E, Ferrari F, Ravaggi A, Romani C, Facchetti F, Sartori E, Odicino FE, Silasi DA, Litkouhi B, Ratner E, Azodi M, Schwartz PE, Santin AD. Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro. Gynecologic Oncology 2016, 144: 146-152. PMID: 27894751, PMCID: PMC5183545, DOI: 10.1016/j.ygyno.2016.11.023.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsCarboplatinCarcinomaCD4 Lymphocyte CountCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell SurvivalDisease-Free SurvivalDNA Polymerase IIDrug Resistance, NeoplasmEndometrial NeoplasmsFemaleHumansMicrosatellite InstabilityMiddle AgedMutationPoly-ADP-Ribose Binding ProteinsTumor Cells, CulturedConceptsBetter prognosisTumor cell linesInfiltration of CD4Number of CD4Platinum-based chemotherapyT lymphocyte infiltrationPD-1 receptorCell linesLow metastatic capabilityPOLE-mutated tumorsWild-type ECsEC cell linesLymphocyte infiltrationFavorable prognosisPD-1EC patientsType tumorsEnhanced immunogenicityT lymphocytesMolecular subtypesTumors correlatesChemotherapyMetastatic capabilityPrognosisTumorsPlatinum desensitization in patients with carboplatin hypersensitivity: A single-institution retrospective study
Altwerger G, Gressel GM, English DP, Nelson WK, Carusillo N, Silasi DA, Azodi M, Santin A, Schwartz PE, Ratner ES. Platinum desensitization in patients with carboplatin hypersensitivity: A single-institution retrospective study. Gynecologic Oncology 2016, 144: 77-82. PMID: 27789084, DOI: 10.1016/j.ygyno.2016.09.027.Peer-Reviewed Original ResearchConceptsPositive skin testsHypersensitivity reactionsDesensitization protocolSkin testCarboplatin infusionLife-threatening hypersensitivity reactionSingle-institution retrospective studyCarboplatin desensitization protocolPrior hypersensitivity reactionMajority of patientsCarboplatin hypersensitivity reactionsCarboplatin hypersensitivityPulmonary hypertensionAdverse eventsRetrospective reviewRetrospective studyGynecologic cancerGrade 0Patient deathRisk factorsCardiac conditionsPatientsLarger studyInfusionAgeMutational landscape of uterine and ovarian carcinosarcomas implicates histone genes in epithelial–mesenchymal transition
Zhao S, Bellone S, Lopez S, Thakral D, Schwab C, English DP, Black J, Cocco E, Choi J, Zammataro L, Predolini F, Bonazzoli E, Bi M, Buza N, Hui P, Wong S, Abu-Khalaf M, Ravaggi A, Bignotti E, Bandiera E, Romani C, Todeschini P, Tassi R, Zanotti L, Odicino F, Pecorelli S, Donzelli C, Ardighieri L, Facchetti F, Falchetti M, Silasi DA, Ratner E, Azodi M, Schwartz PE, Mane S, Angioli R, Terranova C, Quick CM, Edraki B, Bilgüvar K, Lee M, Choi M, Stiegler AL, Boggon TJ, Schlessinger J, Lifton RP, Santin AD. Mutational landscape of uterine and ovarian carcinosarcomas implicates histone genes in epithelial–mesenchymal transition. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 12238-12243. PMID: 27791010, PMCID: PMC5087050, DOI: 10.1073/pnas.1614120113.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overCarcinosarcomaClass I Phosphatidylinositol 3-KinasesDNA-Binding ProteinsEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHistonesHumansMiddle AgedMutationOvarian NeoplasmsPTEN PhosphohydrolaseTelomeraseTumor Suppressor Protein p53Uterine NeoplasmsConceptsEpithelial-mesenchymal transitionWhole-exome sequencingHistone gene clusterMutational landscapeStable transgenic expressionExcess of mutationsMultiregion whole-exome sequencingHistone genesEvolutionary historyPhylogenetic relationshipsGene clusterHistone H2AChromosome segmentsSeparate lineagesCancer genesGenetic landscapeUterine serous carcinoma cell linesTransgenic expressionGenesCarcinoma cell linesGene TP53Frequent amplificationFrequent deletionsChromosome 6pInvasive propertiesSYD985, 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 HER2Efficacy and tolerability of combination cisplatin and ifosfamide chemotherapy with vaginal cuff brachytherapy in the first line treatment of uterine carcinosarcoma.
Abu-Khalaf MM, Raza MA, Hatzis C, Wang H, Lin K, Higgins S, Ratner E, Silasi DA, Azodi M, Rutherford TJ, Santin AD, Schwartz PE. Efficacy and tolerability of combination cisplatin and ifosfamide chemotherapy with vaginal cuff brachytherapy in the first line treatment of uterine carcinosarcoma. European Journal Of Gynaecological Oncology 2016, 37: 199-203. PMID: 27172745.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnemiaAntineoplastic Combined Chemotherapy ProtocolsBrachytherapyCarcinosarcomaChemoradiotherapyCisplatinDisease-Free SurvivalFemaleHumansIfosfamideMesnaMiddle AgedNeoplasm StagingNeutropeniaProtective AgentsRetrospective StudiesTreatment OutcomeUterine NeoplasmsConceptsVaginal cuff brachytherapyProgression-free survivalFirst-line treatmentOverall survivalUterine carcinosarcomaStage ILine treatmentStage IIIDay 1Anemia grade 1Most common toxicitiesNeutropenia grade 3Cycles of cisplatinMedian overall survivalStage IV diseaseCommon toxicitiesMedian followTreatment discontinuationFree survivalPatient withdrawalCombination cisplatinDose modificationMedian ageRetrospective studyGrade 3
2014
Identification of Optimal Reference Genes for Gene Expression Normalization in a Wide Cohort of Endometrioid Endometrial Carcinoma Tissues
Romani C, Calza S, Todeschini P, Tassi RA, Zanotti L, Bandiera E, Sartori E, Pecorelli S, Ravaggi A, Santin AD, Bignotti E. Identification of Optimal Reference Genes for Gene Expression Normalization in a Wide Cohort of Endometrioid Endometrial Carcinoma Tissues. PLOS ONE 2014, 9: e113781. PMID: 25473950, PMCID: PMC4256201, DOI: 10.1371/journal.pone.0113781.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdultAgedAged, 80 and overCarcinoma, EndometrioidCohort StudiesEndometriumFemaleGene Expression Regulation, NeoplasticGlyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)HumansMiddle AgedNeoplasm StagingOvarian NeoplasmsReal-Time Polymerase Chain ReactionReference ValuesRNARNA, Ribosomal, 18SSoftwareConceptsEndometrial cancer tissuesEndometrial cancer samplesEndometrial carcinoma tissuesHigh-grade tumorsNormal endometrial tissuesEndometrial tumor samplesReal-time RT-PCRGreen real-time RT-PCRSYBR Green real-time RT-PCRTumor degreeEndometrial tissueEndometrial samplesTumor gradeUse of PPIAStudy groupHPRT1 expressionQRT-PCR techniqueCancer tissuesCarcinoma tissuesWider cohortTumor samplesCancer samplesRT-PCRExpression levelsSignificant differencesAfatinib 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 xenograftsSolitomab, an epithelial cell adhesion molecule/CD3 bispecific antibody (BiTE), is highly active against primary chemotherapy‐resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo
English DP, Bellone S, Schwab CL, Roque DM, Lopez S, Bortolomai I, Cocco E, Bonazzoli E, Chatterjee S, Ratner E, Silasi D, Azodi M, Schwartz PE, Rutherford TJ, Santin AD. Solitomab, an epithelial cell adhesion molecule/CD3 bispecific antibody (BiTE), is highly active against primary chemotherapy‐resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo. Cancer 2014, 121: 403-412. PMID: 25251053, PMCID: PMC4304922, DOI: 10.1002/cncr.29062.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, BispecificAntigens, NeoplasmCarcinoma, Ovarian EpithelialCD3 ComplexCell Adhesion MoleculesCell Line, TumorCytotoxicity, ImmunologicDrug Resistance, NeoplasmEpithelial Cell Adhesion MoleculeFemaleFlow CytometryHumansMiddle AgedNeoplasms, Glandular and EpithelialOvarian NeoplasmsT-LymphocytesConceptsOvarian cancer cell linesPeripheral blood lymphocytesTumor cellsCancer cell linesFlow cytometryBlood lymphocytesCell linesMalignant cellsChemotherapy-resistant cell linesChemotherapy-resistant ovarian cancerT cell-mediated killingT-cell activation markersCell-mediated cytotoxicity assayEpCAM expressionPrimary ovarian cancer cell linesFresh ovarian tumorsChemotherapy-resistant diseaseCD3 bispecific antibodyTumor-associated lymphocytesEpithelial ovarian carcinoma cell linesT cell cytotoxicityChromium release assaysFresh tumor cellsOvarian tumor cell linesOvarian tumor cellsTaselisib, a selective inhibitor of PIK3CA, is highly effective on PIK3CA-mutated and HER2/neu amplified uterine serous carcinoma in vitro and in vivo
Lopez S, Schwab CL, Cocco E, Bellone S, Bonazzoli E, English DP, Schwartz PE, Rutherford T, Angioli R, Santin AD. Taselisib, a selective inhibitor of PIK3CA, is highly effective on PIK3CA-mutated and HER2/neu amplified uterine serous carcinoma in vitro and in vivo. Gynecologic Oncology 2014, 135: 312-317. PMID: 25172762, PMCID: PMC4270135, DOI: 10.1016/j.ygyno.2014.08.024.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntineoplastic AgentsCarcinomaCell Cycle CheckpointsCell Line, TumorCell ProliferationClass I Phosphatidylinositol 3-KinasesDrug Screening Assays, AntitumorFemaleGene AmplificationHumansImidazolesIn Situ Hybridization, FluorescenceIn Vitro TechniquesMiceMiddle AgedNeoplasms, Cystic, Mucinous, and SerousOxazepinesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsReceptor, ErbB-2Uterine NeoplasmsXenograft Model Antitumor AssaysConceptsHER2/neu gene amplificationUterine serous carcinomaUSC cell linesNeu gene amplificationCell linesHER2/neuPIK3CA mutationsGene amplificationPhosphorylation of S6Serous carcinomaPIK3CA wild typeG0/G1 phaseSelective inhibitorOncogenic PIK3CA mutationsS6 proteinCell cycle distributionPrimary uterine serous carcinomaWild typeDownstream signalingPrimary USC cell linesCell cycleNovel therapeutic optionsDose-dependent increaseDifferential growth inhibitionG1 phase