2024
Preclinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition in low grade serous ovarian cancer
McNamara B, Demirkiran C, Hartwich T, Bellone S, Manavella D, Mutlu L, Greenman M, Zipponi M, Yang-Hartwich Y, Yang K, Ratner E, Schwartz P, Coma S, Pachter J, Santin A. Preclinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition in low grade serous ovarian cancer. Gynecologic Oncology 2024, 183: 133-140. PMID: 38493021, DOI: 10.1016/j.ygyno.2024.01.028.Peer-Reviewed Original ResearchLow grade serous ovarian carcinomaWhole-exome-sequencingGain-of-function mutationsVS-4718Preclinical efficacyLow grade serous ovarian cancerSerous ovarian cancerControl-treated miceTumor growth inhibitionWild-type KRASLoss of heterozygosityDecreased p-ERKRAF/MEK inhibitionMedian survivalOvarian cancerRecurrence rateTherapeutic optionsOral gavageTumor growthTumor samplesIn vivo activityMAPK pathway genesRAF/MEK inhibitorsP-ERKEx vivo
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 vehicleHomologous recombination deficiency (HRD) signature-3 in ovarian and uterine carcinosarcomas correlates with preclinical sensitivity to Olaparib, a poly (adenosine diphosphate [ADP]- ribose) polymerase (PARP) inhibitor
Tymon-Rosario JR, Manara P, Manavella DD, Bellone S, Hartwich TMP, Harold J, Yang-Hartwich Y, Zipponi M, Choi J, Jeong K, Mutlu L, Yang K, Altwerger G, Menderes G, Ratner E, Huang GS, Clark M, Andikyan V, Azodi M, Schwartz PE, Alexandrov LB, Santin AD. Homologous recombination deficiency (HRD) signature-3 in ovarian and uterine carcinosarcomas correlates with preclinical sensitivity to Olaparib, a poly (adenosine diphosphate [ADP]- ribose) polymerase (PARP) inhibitor. Gynecologic Oncology 2022, 166: 117-125. PMID: 35599167, DOI: 10.1016/j.ygyno.2022.05.005.Peer-Reviewed Original ResearchConceptsUterine carcinosarcomaCS cell linesSignature 3Cell linesPolymerase inhibitorsOverall animal survivalFresh tumor samplesPoly (ADP-ribose) polymerase (PARP) inhibitorsXenograft tumor growthG2/M phaseAggressive malignancyCS patientsPrimary tumorCell cycle arrestPrimary cell linesPoor survivalClinical studiesPreclinical sensitivityCarcinosarcomaTumor growthAnimal survivalOlaparib activityTumor samplesOlaparibAntitumor activity
2018
Claudin3 is localized outside the tight junctions in human carcinomas
Corsini M, Ravaggi A, Odicino F, Santin AD, Ravelli C, Presta M, Romani C, Mitola S. Claudin3 is localized outside the tight junctions in human carcinomas. Oncotarget 2018, 9: 18446-18453. PMID: 29719617, PMCID: PMC5915084, DOI: 10.18632/oncotarget.24858.Peer-Reviewed Original ResearchExpression of Claudin3Tight junction proteinsTight junctionsEpithelial-derived tumorsProstate carcinomaOncomine databaseClaudin3Tumor samplesCBioPortal databaseTumoral tissueGene alterationsHuman carcinomasTherapeutic drugsTissue samplesJunction proteinsNovel diagnostic probesHealthy tissueImmunofluorescence analysisCarcinomaTumorsNumber alterationsTissueAlterationsSurgeryBladder
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 differences
2010
HER-2/NEU overexpression in vulvar Paget disease: the Yale experience
Richter CE, Hui P, Buza N, Silasi DA, Azodi M, Santin AD, Schwartz PE, Rutherford TJ. HER-2/NEU overexpression in vulvar Paget disease: the Yale experience. Journal Of Clinical Pathology 2010, 63: 544. PMID: 20418225, DOI: 10.1136/jcp.2010.077446.Peer-Reviewed Original ResearchConceptsVulvar Paget's diseasePaget's diseaseNeu overexpressionOutcome dataHER-2/neu expressionHER-2/neuEfficacy of trastuzumabExtensive reconstructive proceduresHigh recurrence rateMedical record searchInteresting treatment optionSurgical treatmentRecurrence rateTreatment optionsNeu expressionClinical trialsReconstructive proceduresTissue microarrayPatientsRecord searchTumor samplesYale experienceDiseaseNeuStaining results
1996
Differential Effects of High-Dose Gamma Irradiation on the Production of Transforming Growth Factor-Beta in Fresh and Established Human Ovarian Cancer
Santin A, Hiserodt J, DiSaia P, Pecorelli S, Granger G. Differential Effects of High-Dose Gamma Irradiation on the Production of Transforming Growth Factor-Beta in Fresh and Established Human Ovarian Cancer. Gynecologic Oncology 1996, 61: 403-408. PMID: 8641623, DOI: 10.1006/gyno.1996.0164.Peer-Reviewed Original ResearchConceptsOvarian carcinoma cell linesCarcinoma cell linesOvarian tumorsFresh tumorsCell linesHigh dosesImmunoinhibitory cytokinesTumor cellsFresh ovarian tumorsTGF-beta secretionTGF-beta productionCytokines TNF-alphaFresh tumor cellsWeak immunological responseFresh tumor samplesHuman ovarian cancerHuman ovarian carcinoma cell linesTNF-alphaOvarian cancerImmunological responseIFN-gammaCytokinesTumorsTumor samplesContinuous cell lines