2020
Modeling biological and genetic diversity in upper tract urothelial carcinoma with patient derived xenografts
Kim K, Hu W, Audenet F, Almassi N, Hanrahan AJ, Murray K, Bagrodia A, Wong N, Clinton TN, Dason S, Mohan V, Jebiwott S, Nagar K, Gao J, Penson A, Hughes C, Gordon B, Chen Z, Dong Y, Watson PA, Alvim R, Elzein A, Gao SP, Cocco E, Santin AD, Ostrovnaya I, Hsieh JJ, Sagi I, Pietzak EJ, Hakimi AA, Rosenberg JE, Iyer G, Vargas HA, Scaltriti M, Al-Ahmadie H, Solit DB, Coleman JA. Modeling biological and genetic diversity in upper tract urothelial carcinoma with patient derived xenografts. Nature Communications 2020, 11: 1975. PMID: 32332851, PMCID: PMC7181640, DOI: 10.1038/s41467-020-15885-7.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBiopsyCamptothecinCarcinoma, Transitional CellFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenetic VariationHigh-Throughput Nucleotide SequencingHumansImmunoconjugatesInterleukin Receptor Common gamma SubunitMaleMiceMice, Inbred NODMice, SCIDMiddle AgedMutationNeoplasm MetastasisNeoplasm TransplantationPhenotypePrecision MedicineProspective StudiesQuinolinesRetrospective StudiesSequence Analysis, RNATrastuzumabUrinary Bladder NeoplasmsUrotheliumConceptsUpper tract urothelial carcinomaUrothelial carcinomaCorresponding patient tumorsEstablishment of patientHigh genomic concordancePersonalized medicine strategiesHER2 kinase inhibitorDisease-specific modelsUTUC patientsCell line modelsPDX modelsBladder cancerTreatment paradigmGenomic concordanceInvasive tumorsSuperior efficacyPatient tumorsPatientsKinase inhibitorsAntibody drugsMedicine strategiesBiological heterogeneityCarcinomaXenograftsTumorsFirst-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 patients
2018
Mutational landscape of primary, metastatic, and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors
Li C, Bonazzoli E, Bellone S, Choi J, Dong W, Menderes G, Altwerger G, Han C, Manzano A, Bianchi A, Pettinella F, Manara P, Lopez S, Yadav G, Riccio F, Zammataro L, Zeybek B, Yang-Hartwich Y, Buza N, Hui P, Wong S, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Zizioli V, Odicino F, Pecorelli S, Ardighieri L, Silasi DA, Litkouhi B, Ratner E, Azodi M, Huang GS, Schwartz PE, Lifton RP, Schlessinger J, Santin AD. Mutational landscape of primary, metastatic, and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 116: 619-624. PMID: 30584090, PMCID: PMC6329978, DOI: 10.1073/pnas.1814027116.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAzepinesBRCA1 ProteinBRCA2 ProteinCell Line, TumorClass I Phosphatidylinositol 3-KinasesFemaleHumansMiceMutationNeoplasm MetastasisNeoplasm Recurrence, LocalOvarian NeoplasmsProteinsProto-Oncogene Proteins c-mycTriazolesTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsOvarian cancerWhole-exome sequencingC-myc amplificationRecurrent tumorsPrimary tumorBET inhibitorsChemotherapy-resistant diseaseRecurrent ovarian cancerLethal gynecologic malignancyBilateral ovarian cancerChemotherapy-resistant tumorsPrimary metastatic tumorsMutational landscapeSomatic mutationsFresh-frozen tumorsGynecologic malignanciesMetastatic tumorsPrimary cell linesC-MYC gainPIK3CA amplificationTranscoelomic metastasisTherapeutic targetPatientsMetastatic abilityTumors
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
Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer
Yin M, Li X, Tan S, Zhou HJ, Ji W, Bellone S, Xu X, Zhang H, Santin AD, Lou G, Min W. Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer. Journal Of Clinical Investigation 2016, 126: 4157-4173. PMID: 27721235, PMCID: PMC5096908, DOI: 10.1172/jci87252.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsErbB ReceptorsFemaleHeterograftsHumansIntercellular Adhesion Molecule-1Macrophage-1 AntigenMacrophagesMiceMice, NudeNeoplasm MetastasisNeoplasm ProteinsNeoplasm TransplantationOvarian NeoplasmsSpheroids, CellularVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1ConceptsTumor-associated macrophagesOvarian cancerTranscoelomic metastasisTumor cellsICAM-1Mouse modelEpithelial ovarian cancerOvarian cancer growthOvarian cancer metastasisSpheroid formationOvarian cancer progressionVEGF/VEGFRTumor cell proliferationPharmacological blockadeMetastatic cancerColon cancerCancer growthMetastasisAntibody neutralizationTumor growthCancerClinical pathologyCancer metastasisCancer progressionΑMβ2 integrin
2015
Immunotherapy and targeted therapy for cervical cancer: an update
Menderes G, Black J, Schwab CL, Santin AD. Immunotherapy and targeted therapy for cervical cancer: an update. Expert Review Of Anticancer Therapy 2015, 16: 83-98. PMID: 26568261, DOI: 10.1586/14737140.2016.1121108.Peer-Reviewed Original ResearchConceptsCervical cancer patientsCervical cancerCancer patientsImmune check pointsUse of immunotherapyMetastatic cervical cancerPrognosis of patientsActionable driver mutationsTyrosine kinase inhibitorsImmune system interactionsImmunotherapy studiesMedian survivalAngiogenesis inhibitorsChemotherapeutic drugsPatientsDriver mutationsKinase inhibitorsNew therapeuticsCancerNext-generation sequencingImmunotherapyTherapyGeneration sequencingInhibitorsPrognosis
2010
Overexpression of EpCAM in Uterine Serous Papillary Carcinoma: Implications for EpCAM-Specific Immunotherapy With Human Monoclonal Antibody Adecatumumab (MT201)
El-Sahwi K, Bellone S, Cocco E, Casagrande F, Bellone M, Abu-Khalaf M, Buza N, Tavassoli FA, Hui P, Rüttinger D, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Overexpression of EpCAM in Uterine Serous Papillary Carcinoma: Implications for EpCAM-Specific Immunotherapy With Human Monoclonal Antibody Adecatumumab (MT201). Molecular Cancer Therapeutics 2010, 9: 57-66. PMID: 20053761, PMCID: PMC2806489, DOI: 10.1158/1535-7163.mct-09-0675.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmCarcinoma, PapillaryCell Adhesion MoleculesCell Line, TumorCell MembraneCystadenocarcinoma, SerousDrug Resistance, NeoplasmDrug Screening Assays, AntitumorEpithelial Cell Adhesion MoleculeFemaleFlow CytometryGene Expression Regulation, NeoplasticHumansImmunoglobulin GImmunohistochemistryImmunotherapyInterleukin-2Killer Cells, NaturalMiddle AgedNeoplasm MetastasisRNA, MessengerUterine NeoplasmsConceptsUterine serous papillary carcinomaUSPC cell linesNormal endometrial cellsPrimary USPC cell linesAntibody-dependent cellular cytotoxicitySerous papillary carcinomaCellular cytotoxicityPapillary carcinomaCell linesFlow cytometryAdvanced/recurrentStandard treatment modalityCell-dependent cytotoxicityUterine serous carcinomaComplement-dependent cytotoxicitySurface expressionHuman monoclonal antibodyNovel therapeutic strategiesFresh frozen biopsiesHigh surface expressionEpithelial cell adhesion moleculeOverexpression of EpCAMParaffin-embedded tissuesMedian copy numberSerous carcinoma
2008
Claudin‐7 expression in human epithelial ovarian cancer
TASSI RA, BIGNOTTI E, FALCHETTI M, RAVANINI M, CALZA S, RAVAGGI A, BANDIERA E, FACCHETTI F, PECORELLI S, SANTIN AD. Claudin‐7 expression in human epithelial ovarian cancer. International Journal Of Gynecological Cancer 2008, 18: 1262-1271. PMID: 18298564, DOI: 10.1111/j.1525-1438.2008.01194.x.Peer-Reviewed Original ResearchConceptsEpithelial ovarian carcinomaHistologic typeClaudin-7 expressionClaudin-7Ovarian carcinomaOvarian cancerPeritoneal cavityEOC cellsMetastatic epithelial ovarian carcinomaHuman epithelial ovarian cancerCLDN-7 expressionMain histologic typesEpithelial ovarian cancerProtein levelsGrade of differentiationReverse transcription-polymerase chain reactionTranscription-polymerase chain reactionTight junction proteinsNovel diagnostic markerEpithelium cell lineSingle neoplastic cellsHuman normal tissuesPleural effusionPathologic stageInflammatory cells
2007
Gene expression profile of ovarian serous papillary carcinomas: identification of metastasis-associated genes
Bignotti E, Tassi RA, Calza S, Ravaggi A, Bandiera E, Rossi E, Donzelli C, Pasinetti B, Pecorelli S, Santin AD. Gene expression profile of ovarian serous papillary carcinomas: identification of metastasis-associated genes. American Journal Of Obstetrics And Gynecology 2007, 196: 245.e1-245.e11. PMID: 17346539, DOI: 10.1016/j.ajog.2006.10.874.Peer-Reviewed Original ResearchMeSH KeywordsCystadenocarcinoma, SerousFemaleGene Expression ProfilingHumansMiddle AgedNeoplasm MetastasisOvarian NeoplasmsConceptsMetastasis-associated genesGene expressionOverexpression of CXCL12Gene expression profilesGene expression profilingMetastatic ovarian cancerNumber of invasionsHepsin geneHuman genesExpression profilingExpression profilesOligonucleotide microarraysQuantitative real-time polymerase chain reactionOvarian cancerGenesProbe setsPrimary ovarian serous carcinomaOvarian serous papillary carcinomaSerous papillary ovarian carcinomasProtein levelsSerous papillary carcinomaReal-time polymerase chain reactionOvarian serous carcinomaOspCPredictive genes
2002
Novel immunotherapeutic strategies in gynecologic oncology. Dendritic cell-based immunotherapy for ovarian cancer.
Santin AD, Bellone S, Underwood LJ, O'Brien TJ, Ravaggi A, Pecorelli S, Cannon MJ. Novel immunotherapeutic strategies in gynecologic oncology. Dendritic cell-based immunotherapy for ovarian cancer. Minerva Obstetrics And Gynecology 2002, 54: 133-44. PMID: 12032451.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntigens, NeoplasmCancer VaccinesChildClinical Trials as TopicCombined Modality TherapyDendritic CellsFemaleGPI-Linked ProteinsHumansImmunohistochemistryImmunotherapyKallikreinsMatrix Metalloproteinase 7Membrane ProteinsNeoplasm MetastasisOvarian NeoplasmsSerine EndopeptidasesT-Lymphocytes, CytotoxicTumor Cells, CulturedConceptsTumor antigensOvarian cancerChemotherapy-resistant ovarian cancerOvarian tumor-associated antigensDendritic cell-based immunotherapyTumor-specific immune responsesEffective tumor antigensTherapeutic DC vaccinationNovel immunotherapeutic strategiesStandard treatment modalityCell-based immunotherapyOvarian tumor antigenSpecific immune responseTumor-associated antigensPotential of DCDC vaccinationImmunotherapeutic strategiesDendritic cellsCancer vaccinationCancer patientsGynecologic oncologyTreatment modalitiesNatural adjuvantImmune responseAntigen preparations
1994
Follow-up after Primary Therapy: Management of the Symptomatic Patient—Surgery
Pecorelli S, Sartori E, Santin A. Follow-up after Primary Therapy: Management of the Symptomatic Patient—Surgery. Gynecologic Oncology 1994, 55: s138-s142. PMID: 7835798, DOI: 10.1006/gyno.1994.1353.Peer-Reviewed Original ResearchConceptsSecondary surgeryStage IIICCisplatin chemotherapyStage INegative second-look surgeryMacroscopic residual tumorNegative second lookSecond-line chemotherapyEvidence of diseaseResidual tumor volumeSecond-look surgeryImportant prognostic parameterBowel obstructionPelvic recurrencePrimary surgeryPrimary therapyMost patientsPalliative roleResidual tumorPatients surgeryPrognostic parametersDefinitive procedureDegree of differentiationVisible tumorTumor volume