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
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