2024
Utility of next generation sequencing to unequivocally establish clonality in synchronous vs metastatic endometrial and ovarian carcinomas
Greenman M, Bellone S, Hartwich T, Buza N, Santin A. Utility of next generation sequencing to unequivocally establish clonality in synchronous vs metastatic endometrial and ovarian carcinomas. Gynecologic Oncology Reports 2024, 56: 101524. PMID: 39435258, PMCID: PMC11492078, DOI: 10.1016/j.gore.2024.101524.Peer-Reviewed Original ResearchOvarian carcinomaNext generation sequencingPrimary uterine tumorsDiagnostically challenging casesOvarian tumorsPrimary tumorUterine tumorsEndometrial malignancyMetastatic tumorsAdjuvant treatmentClonal relationshipTargeted therapyUtilization of next generation sequencingTumor clonalityGeneration sequencingProtein expression profilesTumorChallenging casesImprove outcomesCarcinomaGold standardGenetic landscapeMalignancyClonalityExpression profiles
2022
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
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
2020
Derangements 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/mutation
2019
In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma
Han C, Perrone E, Zeybek B, Bellone S, Tymon-Rosario J, Altwerger G, Menderes G, Feinberg J, Haines K, Muller Karger ME, Bianchi A, Zammataro L, Manzano A, Bonazzoli E, Manara P, Buza N, Hui P, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Lopez S, Santin AD. In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma. Gynecologic Oncology 2019, 156: 430-438. PMID: 31839338, DOI: 10.1016/j.ygyno.2019.11.018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmCamptothecinCell Adhesion MoleculesCell Line, TumorCystadenocarcinoma, SerousFemaleFlow CytometryHumansImmunoconjugatesImmunohistochemistryMiceMice, SCIDMolecular Targeted TherapyRandom AllocationTissue Array AnalysisUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaCell surface antigen 2Sacituzumab govitecanTrop-2 expressionTrop-2Serous carcinomaAntigen 2Advanced/recurrent diseasePrimary uterine serous carcinomaResistant human tumorsSignificant bystander killingUSC patientsUSC xenograftsRecurrent diseaseClinical responseEndometrial cancerAggressive variantPoor prognosisPreclinical activityPrimary tumorIntravenous administrationClinical developmentUSC samplesActive metaboliteSN-3893 Sacituzumab govitecan in uterine and ovarian carcinosarcomas
Lopez S, Perrone E, Zeybek B, Bellone S, Manzano A, Zammataro L, Han C, Altwerger G, Angioli R, Santin A. 93 Sacituzumab govitecan in uterine and ovarian carcinosarcomas. International Journal Of Gynecological Cancer 2019, 29: a48. DOI: 10.1136/ijgc-2019-igcs.93.Peer-Reviewed Original ResearchCS cell linesAntibody-drug conjugatesSacituzumab govitecanTrop-2 expressionTrop-2Negative tumorsCell linesControl antibody drug conjugatesNovel antibody-drug conjugateAggressive gynecologic malignancyGreater antitumor effectPrimary tumor cell linesRemarkable antitumor activityAggressive carcinosarcomasGynecologic malignanciesOvarian carcinosarcomaPrimary tumorClinical trialsEpithelial tumorsSarcomatous elementsAntitumor effectsAntigen 2CarcinosarcomaActive metaboliteSN-38
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
2007
Overexpression of Clostridium perfringens Enterotoxin Receptors Claudin-3 and Claudin-4 in Uterine Carcinosarcomas
Santin AD, Bellone S, Siegel ER, McKenney JK, Thomas M, Roman JJ, Burnett A, Tognon G, Bandiera E, Pecorelli S. Overexpression of Clostridium perfringens Enterotoxin Receptors Claudin-3 and Claudin-4 in Uterine Carcinosarcomas. Clinical Cancer Research 2007, 13: 3339-3346. PMID: 17545541, DOI: 10.1158/1078-0432.ccr-06-3037.Peer-Reviewed Original ResearchConceptsCarcinosarcoma cell lineClaudin-3Claudin-4Uterine carcinosarcomaClaudin-4 protein expressionCell linesClaudin-4 receptorsCytotoxic Clostridium perfringensNormal endometrial cellsTumor cell necrosisType-specific therapiesImmunodeficient mouse xenograftsAggressive uterine tumorsHigh-affinity receptorQuantitative reverse transcription PCREndometrial cancerAggressive variantUterine tumorsTumor disappearancePrimary tumorReverse transcription-PCREndometrial cellsNovel therapiesReceptor expressionTherapeutic effect
1998
Routine Lymph Node Dissection in the Treatment of Early Stage Cancer:Are We Doing the Right Thing?
Santin A, Parham G. Routine Lymph Node Dissection in the Treatment of Early Stage Cancer:Are We Doing the Right Thing? Gynecologic Oncology 1998, 68: 1-3. PMID: 9454650, DOI: 10.1006/gyno.1997.4900.Peer-Reviewed Original ResearchConceptsLymph node dissectionNode dissectionLymph nodesProphylactic lymph node dissectionRoutine lymph node dissectionRegional lymph nodesRecent immunological studiesTreatment of patientsEarly-stage solid tumorsEarly-stage cancerEarly-stage malignanciesManagement of cancerElective lymphadenectomyTherapeutic dissectionAntitumor reactivitySalvage rateBloc resectionSurgical interventionPrimary tumorRegional nodesStage cancerLymphatic pathwaysMatter of controversySolid tumorsImmune system