2024
Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)
Sheth S, Oh J, Bellone S, Siegel E, Greenman M, Mutlu L, McNamara B, Pathy S, Clark M, Azodi M, Altwerger G, Andikyan V, Huang G, Ratner E, Kim D, Iwasaki A, Levi A, Buza N, Hui P, Flaherty S, Schwartz P, Santin A. Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147). Clinical Cancer Research 2024, 30: of1-of10. PMID: 38592381, DOI: 10.1158/1078-0432.ccr-23-3639.Peer-Reviewed Original ResearchConceptsRandomized phase II trialCD4/CD8 T cellsT cellsHPV clearanceArm BNo significant differenceClinical surveillanceRate of HPV clearanceSecondary outcomesPre-neoplastic cervical lesionsCervical intraepithelial neoplasiaT cell infiltrationT cell responsesSignificant differenceCIN3 patientsIntraepithelial neoplasiaArm ACervical lesionsImiquimod groupSurveillance armVaginal suppositoriesProspective trialsArm CHPV vaccinationImiquimod
2022
Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients
Ortigoza MB, Yoon H, Goldfeld KS, Troxel AB, Daily JP, Wu Y, Li Y, Wu D, Cobb GF, Baptiste G, O’Keeffe M, Corpuz MO, Ostrosky-Zeichner L, Amin A, Zacharioudakis IM, Jayaweera DT, Wu Y, Philley JV, Devine MS, Desruisseaux MS, Santin AD, Anjan S, Mathew R, Patel B, Nigo M, Upadhyay R, Kupferman T, Dentino AN, Nanchal R, Merlo CA, Hager DN, Chandran K, Lai JR, Rivera J, Bikash CR, Lasso G, Hilbert TP, Paroder M, Asencio AA, Liu M, Petkova E, Bragat A, Shaker R, McPherson DD, Sacco RL, Keller MJ, Grudzen CR, Hochman JS, Pirofski LA, Rahman F, Ajayi A, Rodriguez S, Ledesma A, Keeling D, Rappoport N, Ebel S, Kim J, Chang M, Chan K, Patel P, Martocci A, Dave S, Darwish Y, Taveras M, Shoyelu V, Xin P, Iturrate E, Moldolsky L, Raimondo B, Mendez S, Hughes P, Sterling S, Lord A, Yaghi S, Veloso K, Sheikh M, Visconti-Ferrara E, Fleming A, Youn H, Jane Fran B, Medina R, McKell R, Khan S, Hamilton T, Sanchez C, Patel N, Cleare L, Vergnolle O, Nakouzi A, Quevedo G, Bortz R, Wirchnianski A, Florez C, Babb R, Ayala J, Tsagaris K, James A, Eke I, Obeidallah A, Sandu O, Sohval S, Serrano-Rahman L, Uehlinger J, Bartash R, Al-Abduladheem A, Gendlina I, Sheridan C, Bortnick A, Eichler J, Kaufman R, Yukelis S, Pennock M, Goggin M, Shen C, Annam J, Khokhar A, Barboto D, Lally B, Lee A, Lee M, Yang X, Allen S, Malaviya A, Moussa O, Park R, Sample R, Bae A, Benoni G, Boerger L, Baker L, Luther M, Ameti L, Briggs N, Golden M, Gormally M, Huang G, Johnson R, Morrison A, Montagna-Hill M, Rivera B, Cortezzo G, Debski K, Nicoletti, DeBenedictis K, Davis R, Marshall C, Duque Cuartas M, Beauchamps L, Bertran-Lopez J, Gonzales Zamora J, Delgado-Lelievre M, Dominguez S, Lee C, Kusack H, Karakeshishyan V, Hajaz A, Deniz D, Garcia G, Dae K, Blenet P, Jaffe D, Olson L, Sabogal D, Blust O, Del Prete Perez V, Bornia C, Rodriguez-Perez V, Calderon V, Ramdev R, Jolly A, Guzman I, Guerra R, Brito S, Hobbs R, Denham R, Dick J, Hernandez M, Nielsen L, Anjum S, Mader S, Stutz T, Mammadova M, Nichols P, Khan T, Boktour M, Castaneda B, Benitez B, Hinojosa E, Guerra B, Ortiz A, Hebbeler-Clark R, McShane P, Hibbard R, Hawkins B, Dohanich E, Wadle C, Greenlee K, Brooks J, Herrick C, Gode A, Bergl P, Hu K, Patel J, Srinivasan S, Graf J, Klis C, Reimer K, Carpenter E, Naczek C, Petersen R, Dex R, Drossart J, Zelten J, Brummitt C, Liang M, Yanny L, Dennison G, Runningen P, Brzezinski B, Fiebig S, Naczek C, Kasdorf M, Parameswaran L, Corcoran A, Rohatgi A, Wronska M, Wu X, Srinivasan R, Deng F, Filardo T, Pendse J, Blaser S, Whyte O, Gallagher J, Thomas O, Ramos D, Sturm-Reganato C, Fong C, Daus I, Payoen A, Chiofolo J, Friedman M, Wu D, Jacobson J, Schneider J, Sarwar U, Wang H, Huebinger R, Dronavalli G, Bai Y, Grimes C, Eldin K, Umana V, Martin J, Heath T, Bello F, Ransford D, Laurent-Rolle M, Shenoi S, Akide-Ndunge O, Thapa B, Peterson J, Knauf K, Patel S, Cheney L, Tormey C, Hendrickson J. Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients. JAMA Internal Medicine 2022, 182: 115-126. PMID: 34901997, PMCID: PMC8669605, DOI: 10.1001/jamainternmed.2021.6850.Peer-Reviewed Original ResearchConceptsCCP recipientsPlacebo recipientsSecondary outcomesSymptom durationHospitalized patientsPrimary outcomeDay 28COVID-19SARS-CoV-2 serostatusSARS-CoV-2 titersWorld Health Organization (WHO) ordinal scaleCOVID-19 convalescent plasmaConvalescent plasma usePlacebo-controlled trialLess daysExploratory subgroup analysisNon-Hispanic blacksSARS-CoV-2CCP efficacyConcomitant medicationsAdverse eventsClinical improvementSymptom onsetConvalescent plasmaMedian ageLenvatinib 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 choicePatientsRandomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial
Powell MA, Filiaci VL, Hensley ML, Huang HQ, Moore KN, Tewari KS, Copeland LJ, Secord AA, Mutch DG, Santin A, Warshal DP, Spirtos NM, DiSilvestro PA, Ioffe OB, Miller DS. Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial. Journal Of Clinical Oncology 2022, 40: 968-977. PMID: 35007153, PMCID: PMC8937015, DOI: 10.1200/jco.21.02050.Peer-Reviewed Original ResearchConceptsProgression-free survivalUterine carcinosarcomaOvarian carcinosarcomaEligible patientsHazard ratioMore patientsPC armMedian progression-free survivalRandomized phase III trialNRG Oncology trialsPhase III trialsPI armsGenitourinary hemorrhageHematologic toxicityMedian OSIII trialsLonger OSStandard treatmentGreater death rateStage IIINoninferiority designOncology trialsPatientsStage IStage IV
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
Neratinib in patients with HER2-mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial
Oaknin A, Friedman CF, Roman LD, D’Souza A, Brana I, Bidard F, Goldman J, Alvarez EA, Boni V, ElNaggar AC, Passalacqua R, T.M. K, Santin AD, Keyvanjah K, Xu F, Eli LD, Lalani AS, Bryce RP, Hyman DM, Meric-Bernstam F, Solit DB, Monk BJ. Neratinib in patients with HER2-mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial. Gynecologic Oncology 2020, 159: 150-156. PMID: 32723675, PMCID: PMC8336424, DOI: 10.1016/j.ygyno.2020.07.025.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultDiarrheaFemaleHumansKaplan-Meier EstimateMiddle AgedMutationNauseaNeoplasm Recurrence, LocalProgression-Free SurvivalProtein Kinase InhibitorsQuinolinesReceptor, ErbB-2Response Evaluation Criteria in Solid TumorsSeverity of Illness IndexUterine Cervical NeoplasmsConceptsProgression-free survivalClinical benefit rateObjective response rateCervical cancerOverall survivalHER2 mutationsBasket trialsMetastatic/recurrent cervical cancerAdvanced/recurrent diseaseMedian progression-free survivalCommon HER2 mutationsGrade 3 diarrheaGrade 4 eventsHER2-mutant cancersSafety of neratinibCommon adverse eventsMedian overall survivalRecurrent cervical cancerMetastatic cervical cancerNew safety signalsPhase II basket trialPlatinum-based treatmentTyrosine kinase inhibitorsWarrants further investigationEligible patientsStage 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 samplingDerangements 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/mutationFirst-in-Human, Multicenter, Phase I Dose-Escalation and Expansion Study of Anti-Mesothelin Antibody–Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors
Hassan R, Blumenschein GR, Moore KN, Santin AD, Kindler HL, Nemunaitis JJ, Seward SM, Thomas A, Kim SK, Rajagopalan P, Walter AO, Laurent D, Childs BH, Sarapa N, Elbi C, Bendell JC. First-in-Human, Multicenter, Phase I Dose-Escalation and Expansion Study of Anti-Mesothelin Antibody–Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors. Journal Of Clinical Oncology 2020, 38: 1824-1835. PMID: 32213105, PMCID: PMC7255978, DOI: 10.1200/jco.19.02085.Peer-Reviewed Original ResearchConceptsAnetumab ravtansineDose-escalation cohortsMetastatic solid tumorsAnti-mesothelin antibodySolid tumorsExpansion cohortClinical activityCommon drug-related adverse eventsDrug-related adverse eventsPhase I Dose-EscalationMultiple solid tumor typesPhase IDose-expansion studyI Dose-EscalationPeripheral sensory neuropathyPhase II studyRecurrent ovarian cancerRecurrent solid tumorsPreliminary antitumor activityDrug-related deathsFavorable pharmacokinetic profileSolid tumor typesAntibody-drug conjugatesStable diseaseAdult patientsPhase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002)
Santin AD, Deng W, Frumovitz M, Buza N, Bellone S, Huh W, Khleif S, Lankes HA, Ratner ES, O'Cearbhaill RE, Jazaeri AA, Birrer M. Phase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002). Gynecologic Oncology 2020, 157: 161-166. PMID: 31924334, PMCID: PMC7127981, DOI: 10.1016/j.ygyno.2019.12.034.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsRecurrent cervical cancerPD-L1 expressionPlatinum-based chemotherapyCervical cancerStable diseaseGrade 3 treatment-related adverse eventsGrade 4 treatment-related adverse eventsGrade 5 treatment-related adverse eventsECOG PS 0Prior systemic therapyRecurrent cervical carcinomaResponse/toxicitySingle-agent nivolumabSystemic chemotherapy regimenTolerability of nivolumabImmune checkpoint inhibitorsPercent of patientsAcceptable safety profilePhase II trialKey eligibility criteriaPhase II evaluationECOG PSNivolumab 3RECIST 1.1
2019
PARP-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 activityAdjuvant 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 IProgestinsMonthsSarcomaDiseaseTreatmentSacituzumab 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 reactionsPI3K 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 mortalityRecurrence
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 protocolMicroRNA 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
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 agentFOXM1 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