2020
Randomized Phase II Trial of Carboplatin–Paclitaxel Compared with Carboplatin–Paclitaxel–Trastuzumab in Advanced (Stage III–IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis
Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers S, Secord AA, Havrilesky L, O'Malley DM, Backes FJ, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi K, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin–Paclitaxel Compared with Carboplatin–Paclitaxel–Trastuzumab in Advanced (Stage III–IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis. Clinical Cancer Research 2020, 26: 3928-3935. PMID: 32601075, PMCID: PMC8792803, DOI: 10.1158/1078-0432.ccr-20-0953.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsCarboplatinChemotherapy, AdjuvantCystadenocarcinoma, SerousCytoreduction Surgical ProceduresDrug Administration ScheduleEndometrial NeoplasmsEndometriumFemaleFollow-Up StudiesHumansMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingPaclitaxelProgression-Free SurvivalReceptor, ErbB-2Survival AnalysisTrastuzumabConceptsProgression-free survivalRandomized phase II trialPhase II trialOverall survivalHER2/neuStage IIICarboplatin-paclitaxelII trialRecurrent diseaseControl armSurvival analysisRecurrent uterine serous carcinomaCarboplatin/paclitaxelUterine serous carcinomaOverall survival analysisEvaluable patientsEligible patientsPrimary endpointSecondary endpointsEndometrial cancerAggressive variantSerous carcinomaPrimary treatmentSurvival medianPatientsDerangements 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/mutationLaparoscopic Posterior Versus Lateral Transversus Abdominis Plane Block in Gynecology
Benabou K, Kim S, Tierney CH, Messom JE, Kyriakides TC, Kashani SM, Silasi DA, Azodi M, Seifi F. Laparoscopic Posterior Versus Lateral Transversus Abdominis Plane Block in Gynecology. JSLS Journal Of The Society Of Laparoscopic & Robotic Surgeons 2020, 24: e2020.00032. PMID: 32831540, PMCID: PMC7434395, DOI: 10.4293/jsls.2020.00032.Peer-Reviewed Original ResearchConceptsTransversus abdominis plane blockPostoperative pain scoresLaparoscopic gynecologic surgeryTAP blockPain scoresGynecologic surgeryPlane blockLateral transversus abdominis plane blockLateral TAP blockPosterior TAP blockTAP block groupBody mass indexDemographic characteristicsPre-operative diagnosisLength of stayRegional anesthesia techniquesDifferent operative proceduresInvasive gynecologic surgeryLaparoscopic posteriorNarcotic intakeOpioid consumptionAnesthesiologists classificationNarcotic usagePostoperative painAnalgesic effect
2019
Adjuvant Hormonal Therapy for Low-Grade Endometrial Stromal Sarcoma
Deshmukh U, Black J, Perez-Irizarry J, Passarelli R, Levy K, Rostkowski A, Hui P, Rutherford TJ, Santin AD, Azodi M, Silasi DA, Ratner E, Litkouhi B, Schwartz PE. Adjuvant Hormonal Therapy for Low-Grade Endometrial Stromal Sarcoma. Reproductive Sciences 2019, 26: 600-608. PMID: 29843577, DOI: 10.1177/1933719118778801.Peer-Reviewed Original ResearchConceptsLow-grade endometrial stromal sarcomaRecurrence-free survivalStage I patientsEndometrial stromal sarcomaAromatase inhibitorsI patientsStage IIStromal sarcomaAdvanced low-grade endometrial stromal sarcomaMean recurrence-free survivalLonger recurrence-free survivalAdjuvant hormonal therapyMedian followProgestin groupUnderwent hysterectomyHormonal therapyDisease recurrenceSide effectsPatientsStage IProgestinsMonthsSarcomaDiseaseTreatmentNiraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial
Moore KN, Secord AA, Geller MA, Miller DS, Cloven N, Fleming GF, Wahner Hendrickson AE, Azodi M, DiSilvestro P, Oza AM, Cristea M, Berek JS, Chan JK, Rimel BJ, Matei DE, Li Y, Sun K, Luptakova K, Matulonis UA, Monk BJ. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. The Lancet Oncology 2019, 20: 636-648. PMID: 30948273, DOI: 10.1016/s1470-2045(19)30029-4.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedBRCA1 ProteinBRCA2 ProteinCanadaCarcinoma, Ovarian EpithelialFallopian Tube NeoplasmsFemaleHumansIndazolesMiddle AgedMutationOvarian NeoplasmsPeritoneal NeoplasmsPiperidinesPoly(ADP-ribose) Polymerase InhibitorsProgression-Free SurvivalTime FactorsUnited StatesYoung AdultConceptsProportion of patientsOvarian cancerAdverse eventsOverall survivalBRCA mutationsCommon treatment-emergent serious adverse eventsCommon drug-related grade 3Treatment-emergent serious adverse eventsWorse treatment-emergent adverse eventsDrug-related grade 3Last platinum-based therapyLater-line treatment optionTreatment-emergent adverse eventsLater-line treatmentPrevious chemotherapy regimensPrimary efficacy populationMedian overall survivalPlatinum-sensitive diseasePrimary peritoneal cancerSerious adverse eventsThird-line therapyLines of therapyNew safety signalsPhase 2 studyPhase 2 trialPI3K 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-erbTen-Year Comparison Study of Type 1 and 2 Endometrial Cancers: Risk Factors and Outcomes
Feinberg J, Albright B, Black J, Lu L, Passarelli R, Gysler S, Whicker M, Altwerger G, Menderes G, Hui P, Santin AD, Azodi M, Silasi DA, Ratner ES, Litkouhi B, Schwartz PE. Ten-Year Comparison Study of Type 1 and 2 Endometrial Cancers: Risk Factors and Outcomes. Gynecologic And Obstetric Investigation 2019, 84: 290-297. PMID: 30602164, DOI: 10.1159/000493132.Peer-Reviewed Original ResearchConceptsType 2 cancerHormone replacement therapyCox regression modelType 2 diseaseRisk factorsEndometrial cancerType 1Use of HRTLess obese patientsBaseline risk factorsEndometrial cancer casesMajor cardiovascular diseasesObese patientsOral contraceptivesOverall survivalClinical courseDiabetes mellitusRetrospective reviewRegression modelsReplacement therapyCardiovascular diseaseCancer casesAdvanced stageHigh mortalityRecurrenceA Novel Approach to Combined Vaginal and Laparoscopic Gynecological Surgery
Tierney C, Chung SH, Feinberg J, Haines K, Yadav G, Azodi M, Menderes G. A Novel Approach to Combined Vaginal and Laparoscopic Gynecological Surgery. JSLS Journal Of The Society Of Laparoscopic & Robotic Surgeons 2019, 23: ejsls.2019.00006. PMID: 31097905, PMCID: PMC6464071, DOI: 10.4293/jsls.2019.00006.Peer-Reviewed Original ResearchConceptsLaparoscopic gynecological surgeryGynecological surgeryCombined vaginalPostoperative complicationsAdnexal surgerySurgical candidatesLaparoscopic surgeryMinor postoperative complicationsPrior abdominal surgeryBenign gynecological surgeryNulliparous patientsPrior laparotomyPostoperative dataTotal hysterectomyAbdominal surgeryLaparoscopic approachMajor complicationsSingle surgeonBenign indicationsCase seriesPelvic abscessAbdominal incisionGynecological proceduresPosterior colpotomyVaginal infections
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 protocolRandomized 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 patients
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 carcinomaSYD985Efficacy 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
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 HER2Influence of robotic-assisted laparoscopic hysterectomy on vaginal cuff healing and brachytherapy initiation in endometrial carcinoma patients
Stahl JM, Park HS, Silasi DA, Azodi M, Damast S. Influence of robotic-assisted laparoscopic hysterectomy on vaginal cuff healing and brachytherapy initiation in endometrial carcinoma patients. Practical Radiation Oncology 2016, 6: 226-232. PMID: 27364883, DOI: 10.1016/j.prro.2015.09.015.Peer-Reviewed Original ResearchConceptsRobotic-assisted laparoscopic hysterectomyVaginal cuff healingEndometrial carcinoma patientsIntravaginal brachytherapyAdjuvant intravaginal brachytherapyCuff healingLaparoscopic hysterectomyCarcinoma patientsEndometrial carcinomaTAH patientsHealing statusHealing timeEarly-stage endometrial carcinomaExternal beam radiation therapyVaginal cuff recurrenceTotal abdominal hysterectomyBeam radiation therapyAbdominal hysterectomySecondary outcomesConsecutive patientsLocal recurrencePrimary outcomeOncology evaluationMean intervalHysterectomyEfficacy 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