2024
Preclinical evaluation of avutometinib and defactinib in high‐grade endometrioid endometrial cancer
Hartwich T, Mansolf M, Demirkiran C, Greenman M, Bellone S, McNamara B, Nandi S, Alexandrov L, Yang‐Hartwich Y, Coma S, Pachter J, Santin A. Preclinical evaluation of avutometinib and defactinib in high‐grade endometrioid endometrial cancer. Cancer Medicine 2024, 13: e70210. PMID: 39240189, PMCID: PMC11378359, DOI: 10.1002/cam4.70210.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBenzamidesCarcinoma, EndometrioidCell Line, TumorCell ProliferationEndometrial NeoplasmsExome SequencingFemaleFocal Adhesion Kinase 1HumansImidazolesMiceNeoplasm GradingOxazepinesProtein Kinase InhibitorsPyrazinesSulfonamidesXenograft Model Antitumor AssaysConceptsFocal adhesion kinaseWhole-exome sequencingEndometrial cancer cell linesVS-4718Cell linesRas/MAPK pathwayPhosphorylated focal adhesion kinaseWestern blot assayWhole-exome sequencing resultsRAF/MEK inhibitionEAC cell linesBlot assayP-FAKGenetic landscapeCell cycleEndometrial cancerGenetic derangementsDefactinibP-MEKGrowth inhibitionRAF/MEKRas/MAPKCell viabilityP-ERKHigh-grade endometrial cancer
2022
Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti-PD-1 Immunotherapy in Endometrial Carcinoma.
Chow RD, Michaels T, Bellone S, Hartwich T, Bonazzoli E, Iwasaki A, Song E, Santin AD. Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti-PD-1 Immunotherapy in Endometrial Carcinoma. Cancer Discovery 2022, 13: 312-331. PMID: 36301137, PMCID: PMC9905265, DOI: 10.1158/2159-8290.cd-22-0686.Peer-Reviewed Original ResearchMeSH KeywordsBrain NeoplasmsDNA Mismatch RepairEndometrial NeoplasmsFemaleHumansImmunotherapyNeoplastic Syndromes, HereditaryConceptsAnti-PD-1 immunotherapyImmune checkpoint blockadeMMRd tumorsNK cellsEndometrial carcinomaICB responseMutation burdenT-cell-driven immunityPhase II clinical trialMMRd endometrial cancersPD-1 inhibitorsMismatch repair-deficient cancersTumor-extrinsic factorsHigh response rateEffector CD8Antitumor immunityEndometrial cancerCancer immunotherapyImmune cellsLonger survivalClinical trialsPrimary resistanceT cellsResponse rateMMRd
2009
Overexpression of Epithelial Cell Adhesion Molecule in Primary, Metastatic, and Recurrent/Chemotherapy-Resistant Epithelial Ovarian Cancer: Implications for Epithelial Cell Adhesion Molecule-Specific Immunotherapy
Bellone S, Siegel ER, Cocco E, Cargnelutti M, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Overexpression of Epithelial Cell Adhesion Molecule in Primary, Metastatic, and Recurrent/Chemotherapy-Resistant Epithelial Ovarian Cancer: Implications for Epithelial Cell Adhesion Molecule-Specific Immunotherapy. International Journal Of Gynecological Cancer 2009, 19: 860-866. PMID: 19574774, DOI: 10.1111/igc.0b013e3181a8331f.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma, Clear CellAdenocarcinoma, MucinousAdultAntigens, NeoplasmAntineoplastic Combined Chemotherapy ProtocolsBlotting, WesternCarcinoma, PapillaryCell Adhesion MoleculesChemotherapy, AdjuvantCystadenocarcinoma, SerousDrug Resistance, NeoplasmEndometrial NeoplasmsEpithelial Cell Adhesion MoleculeFemaleFlow CytometryHumansImmunoenzyme TechniquesMiddle AgedNeoplasm Recurrence, LocalOrganoplatinum CompoundsOvarian NeoplasmsOvaryPrognosisRetrospective StudiesReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSurvival RateTreatment OutcomeTumor Cells, CulturedConceptsRecurrent epithelial ovarian carcinomaEpithelial ovarian carcinomaNormal ovarian tissuesOvarian carcinoma cell linesOvarian carcinomaEpithelial cell adhesion moleculeEp-CAMCarcinoma cell linesCell adhesion moleculeOvarian tissueChemotherapy-resistant epithelial ovarian cancerFlow cytometryCell linesAdhesion moleculesEp-CAM overexpressionStandard treatment modalityCell adhesion molecule expressionOvarian carcinoma patientsEpithelial ovarian cancerPrimary ovarian carcinomasAdhesion molecule expressionSurface expressionAntibody-mediated therapyHuman monoclonal antibodyEpithelial cell adhesion molecule (EpCAM) expression
2002
Induction of tumour-specific CD8+ cytotoxic T lymphocytes by tumour lysate-pulsed autologous dendritic cells in patients with uterine serous papillary cancer
Santin AD, Bellone S, Ravaggi A, Roman JJ, Pecorelli S, Parham GP, Cannon MJ. Induction of tumour-specific CD8+ cytotoxic T lymphocytes by tumour lysate-pulsed autologous dendritic cells in patients with uterine serous papillary cancer. British Journal Of Cancer 2002, 86: 151-157. PMID: 11857027, PMCID: PMC2746546, DOI: 10.1038/sj.bjc.6600026.Peer-Reviewed Original ResearchConceptsAutologous tumor cellsUterine serous papillary cancerAutologous dendritic cellsT cellsPatient 1Patient 3Tumor cellsDendritic cellsPapillary cancerOvarian cancerAutologous tumor target cellsTumor lysate-pulsed DCsAnti-HLA class IUterine serous papillary carcinomaColor flow cytometric analysisCancer-specific CD8Cisplatinum-based chemotherapyLumboaortic lymph nodesPapillary cancer patientsTumor-specific toleranceTumor-specific CD8Intracellular cytokine expressionHigh-grade ovarian cancerT lymphocyte responsesStrong cytolytic activity
2000
Development and Therapeutic Effect of Adoptively Transferred T Cells Primed by Tumor Lysate-Pulsed Autologous Dendritic Cells in a Patient with Metastatic Endometrial Cancer
Santin AD, Hermonat PL, Ravaggi A, Bellone S, Cowan C, Coke C, Pecorelli S, Cannon MJ, Parham GP. Development and Therapeutic Effect of Adoptively Transferred T Cells Primed by Tumor Lysate-Pulsed Autologous Dendritic Cells in a Patient with Metastatic Endometrial Cancer. Gynecologic And Obstetric Investigation 2000, 49: 194-203. PMID: 10729762, DOI: 10.1159/000010246.Peer-Reviewed Original ResearchMeSH KeywordsAgedCD56 AntigenCD8-Positive T-LymphocytesCombined Modality TherapyDendritic CellsEndometrial NeoplasmsFemaleFlow CytometryHepatic ArteryHistocompatibility Antigens Class IHumansImmunophenotypingImmunotherapy, AdoptiveLiver NeoplasmsL-Lactate DehydrogenaseT-LymphocytesTomography, X-Ray ComputedUric AcidConceptsAutologous dendritic cellsDendritic cellsT cellsLiver metastasesEndometrial cancerAutologous Epstein-Barr virus-transformed lymphoblastoid cellsNK-sensitive K562 cellsSerial gamma camera imagingType 1 cytokine biasTumor-specific T cellsTwo-color flow cytometric analysisPeripheral blood T cellsLarge liver metastasesMetastatic endometrial cancerAutologous tumor cellsTumor-specific CD8T cell responsesEpstein-Barr virus-transformed lymphoblastoid cellsSerum uric acidIntracellular IFN-gammaBlood T cellsLactate dehydrogenaseT-cell immunotherapyLarge tumor massSerial time points