2020
Preclinical Activity of Sacituzumab Govitecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2 (Trop-2) Linked to the Active Metabolite of Irinotecan (SN-38), in Ovarian Cancer
Perrone E, Lopez S, Zeybek B, Bellone S, Bonazzoli E, Pelligra S, Zammataro L, Manzano A, Manara P, Bianchi A, Buza N, Tymon-Rosario J, Altwerger G, Han C, Menderes G, Ratner E, Silasi DA, Azodi M, Hui P, Schwartz PE, Scambia G, Santin AD. Preclinical Activity of Sacituzumab Govitecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2 (Trop-2) Linked to the Active Metabolite of Irinotecan (SN-38), in Ovarian Cancer. Frontiers In Oncology 2020, 10: 118. PMID: 32117765, PMCID: PMC7028697, DOI: 10.3389/fonc.2020.00118.Peer-Reviewed Original ResearchTrop-2 expressionEOC cell linesSacituzumab govitecanEpithelial ovarian cancerPrimary tumor cell linesPreclinical activityTrop-2EOC xenograftsOvarian cancerTrophoblast cell surface antigen 2Cell linesActive metaboliteTumor cell linesImpressive anti-tumor activityCell surface antigen 2Lethal gynecologic malignancyHigh ADCC activityAnti-tumor activityParaffin-embedded tumorsSignificant bystander killingGynecologic malignanciesADCC activityEOC tissuesOvarian tumorsClinical trials
2019
51 In vitro and in vivo activity of sacituzumab govitecan, in ovarian cancer
Perrone E, Lopez S, Zeibek B, Bellone S, Zammataro L, Manzano A, Bonazzoli E, Manara P, Scambia G, Santin A. 51 In vitro and in vivo activity of sacituzumab govitecan, in ovarian cancer. International Journal Of Gynecological Cancer 2019, 29: a29. DOI: 10.1136/ijgc-2019-igcs.51.Peer-Reviewed Original ResearchEpithelial ovarian cancerTrop-2 expressionSacituzumab govitecanPrimary tumor cell linesEOC cell linesTrop-2EOC xenograftsOvarian cancerCell linesTumor cell linesAggressive epithelial ovarian cancerLethal gynecologic malignancyHigh ADCC activityGreater antitumor effectParaffin-embedded tumorsGynecologic malignanciesADCC activityOvarian tumorsPreclinical activityClinical trialsEpithelial tumorsSignificant bystander effectAntitumor effectsStrong stainingActive metaboliteHuman Ovarian Cancer Tumor Formation in Severe Combined Immunodeficient (SCID) Pigs
Boettcher AN, Kiupel M, Adur MK, Cocco E, Santin AD, Bellone S, Charley SE, Blanco-Fernandez B, Risinger JI, Ross JW, Tuggle CK, Shapiro EM. Human Ovarian Cancer Tumor Formation in Severe Combined Immunodeficient (SCID) Pigs. Frontiers In Oncology 2019, 9: 9. PMID: 30723704, PMCID: PMC6349777, DOI: 10.3389/fonc.2019.00009.Peer-Reviewed Original ResearchPreclinical animal modelsSCID pigsOvarian carcinomaAnimal modelsEar tissueLate-stage diseaseLethal gynecologic malignancyOvarian cancer researchImmunodeficient pigsGynecologic malignanciesCarcinoma cell linesImmunohistochemical phenotypeCytokeratin 7Ovarian cancerXenotransplantation modelNeck musclesOrthotopic modelTumor massOvCa cellsPapillary carcinoma cell lineCarcinomaControl pigsClaudin-4Claudin-3Tumors
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 abilityTumorsA novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma
Han C, Bellone S, Siegel ER, Altwerger G, Menderes G, Bonazzoli E, Egawa-Takata T, Pettinella F, Bianchi A, Riccio F, Zammataro L, Yadav G, Marto JA, Penet MF, Levine DA, Drapkin R, Patel A, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. A novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma. Gynecologic Oncology 2018, 149: 585-591. PMID: 29572027, PMCID: PMC5986604, DOI: 10.1016/j.ygyno.2018.03.050.Peer-Reviewed Original ResearchConceptsHigh-grade serous ovarian carcinomaSerous ovarian carcinomaIL-6Ovarian cancerOvarian carcinomaE-cadHigh-grade serous ovarian adenocarcinomaEarly-stage ovarian cancerROC analysisEarly detectionMajority of patientsLethal gynecologic malignancyStage ovarian cancerOvarian cancer patientsBenign gynecologic pathologyNon-cancer controlsSerous ovarian adenocarcinomaEffective cancer screeningSerous ovarian cancerMultiple biomarker panelsFour-marker panelHigh differential gene expressionGynecologic malignanciesCA 125IL-1ra
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 agent
2005
Treatment of Chemotherapy-Resistant Human Ovarian Cancer Xenografts in C.B-17/SCID Mice by Intraperitoneal Administration of Clostridium perfringens Enterotoxin
Santin AD, Cané S, Bellone S, Palmieri M, Siegel ER, Thomas M, Roman JJ, Burnett A, Cannon MJ, Pecorelli S. Treatment of Chemotherapy-Resistant Human Ovarian Cancer Xenografts in C.B-17/SCID Mice by Intraperitoneal Administration of Clostridium perfringens Enterotoxin. Cancer Research 2005, 65: 4334-4342. PMID: 15899825, DOI: 10.1158/0008-5472.can-04-3472.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsCarcinoma, PapillaryCell Line, TumorClaudin-3Claudin-4Cystadenocarcinoma, SerousDrug Resistance, NeoplasmEnterotoxinsFemaleHumansInjections, IntraperitonealMembrane ProteinsMiceMice, SCIDMiddle AgedOvarian NeoplasmsReceptors, Cell SurfaceUterine Cervical NeoplasmsXenograft Model Antitumor AssaysConceptsClaudin-4 genesRecurrent ovarian cancerPrimary ovarian tumorsOvarian cancerHuman ovarian cancerOvarian tumorsClaudin-3C.B-17/SCID micePrimary human ovarian cancersHuman ovarian cancer xenograftsCytotoxic Clostridium perfringensOvarian tumor burdenAdvanced stage diseaseChemotherapy-resistant diseaseLethal gynecologic malignancyOvarian cancer xenograftsRecurrent ovarian tumorsRelevant clinical modelInhibited tumor growthSCID mouse xenograftsDose-dependent cytotoxic effectTight junction proteinsHigh-affinity receptorQuantitative reverse transcription PCRClostridium perfringens enterotoxin