2015
Evaluation of a novel human IgG1 anti-claudin3 antibody that specifically recognizes its aberrantly localized antigen in ovarian cancer cells and that is suitable for selective drug delivery
Romani C, Cocco E, Bignotti E, Moratto D, Bugatti A, Todeschini P, Bandiera E, Tassi R, Zanotti L, Pecorelli S, Sartori E, Odicino FE, de Marco A, Santin AD, Ravaggi A, Mitola S. Evaluation of a novel human IgG1 anti-claudin3 antibody that specifically recognizes its aberrantly localized antigen in ovarian cancer cells and that is suitable for selective drug delivery. Oncotarget 2015, 6: 34617-34628. PMID: 26416446, PMCID: PMC4741477, DOI: 10.18632/oncotarget.5315.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeoplasmAntibody AffinityAntineoplastic AgentsBlotting, WesternCell Line, TumorClaudin-3Drug CarriersDrug Delivery SystemsEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryHumansImmunoglobulin GMiceMice, SCIDMicroscopy, ConfocalMicroscopy, FluorescenceOvarian NeoplasmsReal-Time Polymerase Chain ReactionRNA, Small InterferingSurface Plasmon ResonanceTransfectionXenograft Model Antitumor AssaysConceptsClostridium perfringens enterotoxinTumor cellsActive anti-cancer compoundsHuman IgG1 Fc domainHuman ovarian cancer cell linesOvarian cancer cell linesOvarian cancer patientsOvarian carcinoma xenograftsOvarian cancer cellsIgG1 Fc domainCancer cell linesAggressive tumorsCancer patientsCarcinoma xenograftsOncological settingIgG1 antibodiesClaudin3Anti-cancer compoundsChimeric antibodyAntitumor efficacySelective drug deliveryPerfringens enterotoxinCancer cellsAntibodiesFc domainClostridium perfringens enterotoxin C‐terminal domain labeled to fluorescent dyes for in vivo visualization of micrometastatic chemotherapy‐resistant ovarian cancer
Cocco E, Shapiro EM, Gasparrini S, Lopez S, Schwab CL, Bellone S, Bortolomai I, Sumi NJ, Bonazzoli E, Nicoletti R, Deng Y, Saltzman WM, Zeiss CJ, Centritto F, Black JD, Silasi DA, Ratner E, Azodi M, Rutherford TJ, Schwartz PE, Pecorelli S, Santin AD. Clostridium perfringens enterotoxin C‐terminal domain labeled to fluorescent dyes for in vivo visualization of micrometastatic chemotherapy‐resistant ovarian cancer. International Journal Of Cancer 2015, 137: 2618-2629. PMID: 26060989, PMCID: PMC4573336, DOI: 10.1002/ijc.29632.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsTumor fluorescenceChemotherapy-resistant ovarian cancerClaudin-3Human ovarian cancer xenograftsTime of surgeryOvarian cancer patientsNeoadjuvant chemotherapy treatmentOvarian cancer xenograftsHealthy organsVivo visualizationTime of intervalBackground fluorescence ratioClostridium perfringens enterotoxinChemotherapy-naïveMicrometastatic diseaseMalignant ascitesOvarian diseaseResidual diseaseOvarian tumorsCancer patientsCancer xenograftsChemotherapy treatmentIP injectionOvarian cancerClostridium Perfringens Enterotoxin (CPE) and CPE-Binding Domain (c-CPE) for the Detection and Treatment of Gynecologic Cancers
Black JD, Lopez S, Cocco E, Schwab CL, English DP, Santin AD. Clostridium Perfringens Enterotoxin (CPE) and CPE-Binding Domain (c-CPE) for the Detection and Treatment of Gynecologic Cancers. Toxins 2015, 7: 1116-1125. PMID: 25835384, PMCID: PMC4417958, DOI: 10.3390/toxins7041116.Peer-Reviewed Original ResearchConceptsClostridium perfringens enterotoxinClaudin-3Claudin-4Perfringens enterotoxinAggressive human cancer cellsGynecologic malignanciesGynecologic cancerHuman cancer cellsOperative settingHuman tumorsCancer cellsPotential roleTumorsSurface proteinsEnterotoxinTreatmentHigh affinitySurgeryMalignancyCancerCytolysisReceptors
2013
Claudins Overexpression in Ovarian Cancer: Potential Targets for Clostridium Perfringens Enterotoxin (CPE) Based Diagnosis and Therapy
English DP, Santin AD. Claudins Overexpression in Ovarian Cancer: Potential Targets for Clostridium Perfringens Enterotoxin (CPE) Based Diagnosis and Therapy. International Journal Of Molecular Sciences 2013, 14: 10412-10437. PMID: 23685873, PMCID: PMC3676847, DOI: 10.3390/ijms140510412.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsClaudin-3Claudin-4ClaudinsEnterotoxinsFemaleGenetic TherapyHumansOvarian NeoplasmsConceptsClostridium perfringens enterotoxinOvarian cancerClaudin-3Chemotherapy-resistant ovarian cancerPerfringens enterotoxinAggressive solid tumorsTight junction proteinsMalignant human tissuesPotent cytolytic toxinClaudin overexpressionOvarian tumorsSolid tumorsClaudin-4CancerJunction proteinsParacellular permeabilityPotential targetExact roleTumorsAttractive targetHuman tissuesSurface proteinsCytolytic toxinEnterotoxinClaudin family
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
2010
Clostridium perfringens enterotoxin carboxy-terminal fragment is a novel tumor-homing peptide for human ovarian cancer
Cocco E, Casagrande F, Bellone S, Richter CE, Bellone M, Todeschini P, Holmberg JC, Fu HH, Montagna MK, Mor G, Schwartz PE, Arin-Silasi D, Azoudi M, Rutherford TJ, Abu-Khalaf M, Pecorelli S, Santin AD. Clostridium perfringens enterotoxin carboxy-terminal fragment is a novel tumor-homing peptide for human ovarian cancer. BMC Cancer 2010, 10: 349. PMID: 20598131, PMCID: PMC2908101, DOI: 10.1186/1471-2407-10-349.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma, Clear CellAnimalsCarcinoma, PapillaryCarcinoma, Squamous CellChlorocebus aethiopsClaudin-3Claudin-4Clostridium perfringensCystadenocarcinoma, SerousDrug Resistance, NeoplasmEnterotoxinsFemaleFibroblastsFlow CytometryHumansMembrane ProteinsMiceMice, SCIDOvarian NeoplasmsPeptide FragmentsReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSpheroids, CellularTissue DistributionTransplantation, HeterologousTumor Cells, CulturedUterine Cervical NeoplasmsVero CellsConceptsChemotherapy-resistant ovarian cancerClostridium perfringens enterotoxinOvarian cancerOvarian carcinoma cell linesClaudin-3Carcinoma cell linesNovel tumor-homing peptideCarboxy-terminal fragmentTumor cellsResistant ovarian cancer cell linesCell linesNew diagnostic tracersCPE peptideOvarian cancer cell linesResistant ovarian cancer cellsResistant ovarian carcinomaHuman ovarian cancerRelevant animal modelsOvarian tumor cellsOvarian cancer cellsChemotherapy-resistant ovarian cancer cellsHuman epithelial tumorsTime-dependent internalizationCancer cell linesBio-distribution studies
2009
Development and characterization of a human single-chain antibody fragment against claudin-3: a novel therapeutic target in ovarian and uterine carcinomas
Romani C, Comper F, Bandiera E, Ravaggi A, Bignotti E, Tassi RA, Pecorelli S, Santin AD. Development and characterization of a human single-chain antibody fragment against claudin-3: a novel therapeutic target in ovarian and uterine carcinomas. American Journal Of Obstetrics And Gynecology 2009, 201: 70.e1-70.e9. PMID: 19426958, PMCID: PMC3701950, DOI: 10.1016/j.ajog.2009.02.010.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, PapillaryCell Line, TumorCell SeparationClaudin-3Enzyme-Linked Immunosorbent AssayFemaleFlow CytometryGene LibraryHumansImmunoglobulin FragmentsMembrane ProteinsMicroscopy, ConfocalOvarian NeoplasmsSelf-Sustained Sequence ReplicationSensitivity and SpecificitySurface Plasmon ResonanceUterine Cervical NeoplasmsConceptsClaudin-3Uterine serous carcinoma cell linesSerous papillary carcinomaHuman antibody phage display libraryNovel therapeutic targetEnzyme-linked immunosorbent assayEnzyme-linked immunosorbentHuman single-chain antibody fragmentAntibody phage display libraryCarcinoma cell linesUterine carcinomaNovel antitumor agentsPapillary carcinomaTherapeutic targetSingle-chain antibody fragmentHuman antibodiesHuman malignanciesImmunosorbent assayConformational epitopesPhage display libraryCarcinomaCell linesSurface immunofluorescenceCell surface immunofluorescenceAntitumor agents
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 effectOverexpression of claudin‐3 and claudin‐4 receptors in uterine serous papillary carcinoma
Santin AD, Bellone S, Marizzoni M, Palmieri M, Siegel ER, McKenney JK, Hennings L, Comper F, Bandiera E, Pecorelli S. Overexpression of claudin‐3 and claudin‐4 receptors in uterine serous papillary carcinoma. Cancer 2007, 109: 1312-1322. PMID: 17326053, DOI: 10.1002/cncr.22536.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsClaudin-3Claudin-4Clostridium perfringensCystadenocarcinoma, PapillaryCystadenocarcinoma, SerousDrug Resistance, NeoplasmEnterotoxinsFemaleGene ExpressionHumansInjections, IntraperitonealMembrane ProteinsMiceMice, SCIDMiddle AgedReverse Transcriptase Polymerase Chain ReactionRNA, MessengerTumor Cells, CulturedUp-RegulationUterine Cervical NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous papillary carcinomaClaudin-4 receptorsUSPC cell linesSerous papillary carcinomaClaudin-3Endometrial cancerPapillary carcinomaClaudin-4 protein expressionChemotherapy-resistant variantsCytotoxic Clostridium perfringensSublethal intraperitoneal injectionsReverse transcriptase-polymerase chain reactionQuantitative reverse transcriptase-polymerase chain reactionTumor cell necrosisSCID mouse xenograftsType-specific therapiesDose-dependent cytotoxic effectCell linesTight junction proteinsControl tissue samplesHigh-affinity receptorAggressive variantTumor disappearanceIntraperitoneal injectionPolymerase chain reaction
2006
Differential gene expression profiles between tumor biopsies and short-term primary cultures of ovarian serous carcinomas: Identification of novel molecular biomarkers for early diagnosis and therapy
Bignotti E, Tassi RA, Calza S, Ravaggi A, Romani C, Rossi E, Falchetti M, Odicino FE, Pecorelli S, Santin AD. Differential gene expression profiles between tumor biopsies and short-term primary cultures of ovarian serous carcinomas: Identification of novel molecular biomarkers for early diagnosis and therapy. Gynecologic Oncology 2006, 103: 405-416. PMID: 16725184, DOI: 10.1016/j.ygyno.2006.03.056.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBiopsyClaudin-3Claudin-4Cystadenocarcinoma, SerousEpithelial CellsFemaleGene Expression ProfilingHumansImmunohistochemistryKallikreinsMammaglobin AMembrane ProteinsMiddle AgedNeoplasm ProteinsOvarian NeoplasmsReverse Transcriptase Polymerase Chain ReactionTumor Cells, CulturedUteroglobinConceptsGene expression profilesGene expression profilingExpression profilingExpression profilesGenetic fingerprintsDifferential gene expression profilesNovel molecular biomarkersGene expression productsOvarian serous papillary carcinomaGene expression dataHuman genesGene expressionMolecular biomarkersOligonucleotide microarraysExpression productsPrimary tumor cell culturesExpression dataQuantitative RT-PCREnterotoxin receptorGenesMicroarray dataKallikrein 6Ovarian serous carcinomaProtein levelsMammaglobin 2
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