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
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 abilityTumorsInhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer
Bonazzoli E, Predolini F, Cocco E, Bellone S, Altwerger G, Menderes G, Zammataro L, Bianchi A, Pettinella F, Riccio F, Han C, Yadav G, Lopez S, Manzano A, Manara P, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Schlessinger J, Santin AD. Inhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer. Clinical Cancer Research 2018, 24: 4845-4853. PMID: 29941483, PMCID: PMC6168417, DOI: 10.1158/1078-0432.ccr-18-0864.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntineoplastic AgentsApoptosisAurora Kinase AAurora Kinase BAzepinesCell Line, TumorCell ProliferationCystadenocarcinoma, SerousDose-Response Relationship, DrugEndometrial NeoplasmsExome SequencingFemaleGene Expression Regulation, NeoplasticHumansMiceMiddle AgedPhosphorylationPrimary Cell CultureProteinsProto-Oncogene Proteins c-mycTriazolesUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaPrimary USC cell linesUSC cell linesC-myc expressionCell linesC-MycChemotherapy-resistant diseaseQRT-PCRHigh c-myc expressionDose-dependent decreaseDose-dependent increasePotential therapeutic targetEffective therapeutic agentMouse xenograft modelClin Cancer ResFresh frozen tumor tissueC-myc gene amplificationUSC xenograftsEndometrial cancerAggressive variantSerous carcinomaWhole-exome sequencing studiesClinical studiesConcentrations/dosesXenograft model
2011
Serum Human Epididymis Protein 4 and Risk for Ovarian Malignancy Algorithm as New Diagnostic and Prognostic Tools for Epithelial Ovarian Cancer Management
Bandiera E, Romani C, Specchia C, Zanotti L, Galli C, Ruggeri G, Tognon G, Bignotti E, Tassi RA, Odicino F, Caimi L, Sartori E, Santin AD, Pecorelli S, Ravaggi A. Serum Human Epididymis Protein 4 and Risk for Ovarian Malignancy Algorithm as New Diagnostic and Prognostic Tools for Epithelial Ovarian Cancer Management. Cancer Epidemiology Biomarkers & Prevention 2011, 20: 2496-2506. PMID: 22028406, PMCID: PMC3237732, DOI: 10.1158/1055-9965.epi-11-0635.Peer-Reviewed Original ResearchConceptsHuman epididymis protein 4Epithelial ovarian cancerSerum human epididymis protein 4Independent prognostic factorOvarian Malignancy AlgorithmPrognostic factorsMalignancy AlgorithmProgression-free survivalLymph node involvementOvarian cancer managementPreoperative serum samplesProtein 4Ovarian benign cystsElevated CA125Node involvementPositive cytologyPostmenopausal womenPremenopausal womenMultivariable analysisMulticenter studyPrognostic valueAdvanced ageOvarian cancerBenign cystsObstetricians stage
2004
Immunological treatment of ovarian cancer
Cannon MJ, Santin AD, O'Brien TJ. Immunological treatment of ovarian cancer. Current Opinion In Obstetrics & Gynecology 2004, 16: 87-92. PMID: 15128013, DOI: 10.1097/00001703-200402000-00015.Peer-Reviewed Original ResearchConceptsImmunological treatmentOvarian cancerAntibody responseClinical trialsAntigen-specific helper T lymphocytesAdvanced stage ovarian cancerHuman anti-mouse antibody responseAnti-mouse antibody responseImportant target antigenNovel immunological treatmentsDendritic cell vaccinationNovel immunotherapeutic strategiesT cell immunityT lymphocyte responsesStage ovarian cancerHelper T lymphocytesRecent clinical trialsOvarian tumor antigenElicit antibody responsesMouse monoclonal antibodyEvasion of immunityTime of treatmentCell vaccinationRecurrent diseaseImmunotherapeutic strategies
2001
Intrathecal cytotoxic T-cell immunotherapy for metastatic leptomeningeal melanoma.
Clemons-Miller AR, Chatta GS, Hutchins L, Angtuaco EJ, Ravaggi A, Santin AD, Cannon MJ. Intrathecal cytotoxic T-cell immunotherapy for metastatic leptomeningeal melanoma. Clinical Cancer Research 2001, 7: 917s-924s. PMID: 11300492.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, NeoplasmB-LymphocytesCD8-Positive T-LymphocytesCytokinesDendritic CellsEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryGp100 Melanoma AntigenHumansImmunotherapyImmunotherapy, AdoptiveIndiumInterferon-gammaInterleukin-2Interleukin-4Interleukin-6MART-1 AntigenMelanomaMembrane GlycoproteinsMeningeal NeoplasmsMiddle AgedMonophenol MonooxygenaseNeoplasm ProteinsProteinsReverse Transcriptase Polymerase Chain ReactionTime FactorsTissue DistributionT-Lymphocytes, CytotoxicTumor Cells, CulturedTumor Necrosis Factor-alphaConceptsTumor necrosis factor alphaNecrosis factor alphaNeurological symptomsLeptomeningeal melanomaFactor alphaLow-dose IL-2 administrationType 1 cytokine profileAutologous dendritic cellsIL-2 administrationRight carotid arteryIntra-arterial deliveryT-cell immunotherapyGreater lytic activityLoss of hearingCTL infusionCytokine profileAutologous EBVDendritic cellsRecurrent melanomaOmmaya reservoirSpecific CTLIL-6IL-4Specific lysisLower extremities
1997
Multiple cellular proteins are recognized by the adeno‐associated virus Rep78 major regulatory protein and the amino‐half of Rep78 is required for many of these interactions
Hermonat P, Carter C, Parham G, Quirk J, Santin A. Multiple cellular proteins are recognized by the adeno‐associated virus Rep78 major regulatory protein and the amino‐half of Rep78 is required for many of these interactions. IUBMB Life 1997, 43: 409-420. PMID: 9350349, DOI: 10.1080/15216549700204201.Peer-Reviewed Original ResearchConceptsMultiple cellular proteinsCellular proteinsHeterologous gene expressionHuman chromosome 19Multi-functional proteinMajor regulatory proteinSite-specific integrationAAV DNA replicationLarge T antigenRep78 proteinReplication proteinsDNA replicationProtein interactionsRegulatory proteinsTranscriptional levelChromosome 19Rep78Assay systemGene expressionCellular extractsT antigenProteinAAV DNASpecific integrationCoimmunoprecipitation