191 results on '"Califano, D"'
Search Results
2. Alternative academic approaches for testing homologous recombination deficiency in ovarian cancer in the MITO16A/MaNGO-OV2 trial
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Capoluongo, E.D., Pellegrino, B., Arenare, L., Califano, D., Scambia, G., Beltrame, L., Serra, V., Scaglione, G.L., Spina, A., Cecere, S.C., De Cecio, R., Normanno, N., Colombo, N., Lorusso, D., Russo, D., Nardelli, C., D’Incalci, M., Llop-Guevara, A., Pisano, C., Baldassarre, G., Mezzanzanica, D., Artioli, G., Setaro, M., Tasca, G., Roma, C., Campanini, N., Cinieri, S., Sergi, A., Musolino, A., Perrone, F., Chiodini, P., Marchini, S., and Pignata, S.
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- 2022
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3. PARP Inhibitors in Endometrial Cancer: Current Status and Perspectives
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Musacchio L, Caruso G, Pisano C, Cecere SC, Di Napoli M, Attademo L, Tambaro R, Russo D, Califano D, Palaia I, Muzii L, Benedetti Panici P, and Pignata S
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endometrial cancer ,parp inhibitors ,pten mutation ,p53 mutation ,homologous recombination deficiency ,immune checkpoint inhibitors ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Lucia Musacchio,1 Giuseppe Caruso,1 Carmela Pisano,2 Sabrina Chiara Cecere,2 Marilena Di Napoli,2 Laura Attademo,2 Rosa Tambaro,2 Daniela Russo,3 Daniela Califano,3 Innocenza Palaia,1 Ludovico Muzii,1 Pierluigi Benedetti Panici,1 Sandro Pignata2 1Department of Maternal and Child Health and Urological Sciences, University “Sapienza”, Policlinico Umberto I, Rome, Italy; 2Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, Italy; 3Functional Genomic Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, ItalyCorrespondence: Sandro PignataDepartment of Urology and Gynecology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Via Semmola, Naples 80131, ItalyTel +39 0815903409Fax +39 0815903861Email s.pignata@istitutotumori.na.itAbstract: Advanced, recurrent and metastatic endometrial cancer (EC) has a dismal prognosis due to poor response rates to conventional treatments. In the era of precision medicine, the improved understanding of cancer genetics and molecular biology has led to the development of targeted therapies, such as poly (ADP-ribose) polymerase (PARP) inhibitors. This class of drugs that inhibit PARP enzymes has been investigated in many different types of tumors and its use in the treatment of gynecological malignancies has rapidly increased over the past few years. Data from several clinical trials showed that PARP inhibitors have a beneficial role in cancers with a defect in the homologous DNA recombination system, regardless of the BRCA mutational status. Since EC frequently shows mutations in PTEN and TP53 genes, indirectly involved in the homologous DNA recombination pathway, several in vivo and in vitro studies investigated the efficacy of PARP inhibitors in EC, showing promising results. This review will discuss the use of PARP inhibitors in endometrial cancer, summarizing data from preclinical studies and providing an overview of the ongoing trials, with a special focus on the development of combined treatment strategies with PARP inhibitors and immune checkpoint inhibitors.Keywords: endometrial cancer, PARP inhibitors, PTEN mutation, P53 mutation, homologous recombination deficiency, immune checkpoint inhibitors
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- 2020
4. Trabectedin in Ovarian Cancer: is it now a Standard of Care?
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Ventriglia, J., Paciolla, I., Cecere, S.C., Pisano, C., Di Napoli, M., Arenare, L., Setola, S.V., Losito, N.S., Califano, D., Orditura, M., and Pignata, S.
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- 2018
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5. Alternative academic approaches for testing homologous recombination deficiency in ovarian cancer in the MITO16A/MaNGO-OV2 trial
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Capoluongo ED, B, Pellegrino, Arenare L, Califano D, Scambia G, L, Beltrame, V, Serra, Scaglione GL, Spina A, Cecere SC, De Cecio R, N, Normanno, N, Colombo, Lorusso D, Russo D, Nardelli C, M, D'Incalci, Llop-Guevara A, Pisano C, G, Baldassarre, Mezzanzanica D, Artioli G, Setaro M, Tasca G, C, Roma, Campanini N, Cinieri S, A, Sergi, Musolino A, Perrone F, Chiodini P, S, Marchini, Pignata S, Institut Català de la Salut, [Capoluongo ED] Department of Molecular Medicine and Medical Biotechnology, Università degli Studi di Napoli Federico II, Naples, Italy. Azienda Ospedaliera per L'Emergenza, Cannizzaro, Catania, Italy. [Pellegrino B] Department of Medicine and Surgery, University of Parma, Parma, Italy. Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy. Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC), Parma, Italy. [Arenare L] Clinical Trial Unit, Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Naples, Italy. [Califano D] Microenvironment Molecular Targets Unit, Istituto Nazionale Tumori IRCCS – Fondazione G. Pascale, Naples, Italy. [Scambia G] Department of Women and Child Health, Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. Department of Life Science and Public Health, Catholic University of Sacred Heart Largo Agostino Gemelli, Rome, Italy. [Beltrame L] Molecular Pharmacology laboratory, Group of Cancer Pharmacology IRCCS Humanitas Research Hospital, Rozzano, Italy. [Serra V, Guevara A] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Capoluongo, E, Pellegrino, B, Arenare, L, Califano, D, Scambia, G, Beltrame, L, Serra, V, Scaglione, G, Spina, A, Cecere, S, De Cecio, R, Normanno, N, Colombo, N, Lorusso, D, Russo, D, Nardelli, C, D'Incalci, M, Llop-Guevara, A, Pisano, C, Baldassarre, G, Mezzanzanica, D, Artioli, G, Setaro, M, Tasca, G, Roma, C, Campanini, N, Cinieri, S, Sergi, A, Musolino, A, Perrone, F, Chiodini, P, Marchini, S, Pignata, S, Capoluongo, E D, Scaglione, G L, and Cecere, S C
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Cancer Research ,Paclitaxel ,Genetic Phenomena::Recombination, Genetic::Homologous Recombination [PHENOMENA AND PROCESSES] ,Ovaris - Càncer - Aspectes genètics ,neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas [ENFERMEDADES] ,Carboplatin ,Other subheadings::Other subheadings::/genetics [Other subheadings] ,Humans ,Homologous Recombination ,Recombinació genètica ,Platinum ,fenómenos genéticos::recombinación genética::recombinación homóloga [FENÓMENOS Y PROCESOS] ,Ovarian Neoplasms ,Mangifera ,molecular testing ,Otros calificadores::Otros calificadores::/genética [Otros calificadores] ,Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms [DISEASES] ,RD ,HRR ,Myriad ,ovarian cancer ,Ovaris - Càncer - Tractament ,Bevacizumab ,Oncology ,HRD ,Female ,Poly(ADP-ribose) Polymerases - Abstract
Molecular testing; Ovarian cancer Proves moleculars; Càncer d'ovaris Pruebas moleculares; Cáncer de ovarios Background The detection of homologous recombination deficiency (HRD) can identify patients who are more responsive to platinum and poly ADP ribose polymerase inhibitors (PARPi). MyChoice CDx (Myriad) is the most used HRD test in ovarian cancer (OC). However, some limitations of commercial tests exist, because of the high rate of inconclusive results, costs, and the impossibility of evaluating functional resistance mechanisms. Patients and methods Two academic genomic tests and a functional assay, the RAD51 foci, were evaluated to detect HRD. One hundred patients with high-grade OC enrolled in the MITO16A/MaNGO-OV2 trial and treated with first-line therapy with carboplatin, paclitaxel, and bevacizumab were analyzed. Results The failure rate of the two genomic assays was 2%. The sensitivity in detecting HRD when compared with Myriad was 98.1% and 90.6%, respectively. The agreement rate with Myriad was 0.92 and 0.87, with a Cohen’s κ coefficient corresponding to 0.84 and 0.74, respectively. For the RAD51 foci assay, the failure rate was 30%. When the test was successful, discordant results for deficient and proficient tumors were observed, and additional HRD patients were identified compared to Myriad; sensitivity was 82.9%, agreement rate was 0.65, and Cohen’s κ coefficient was 0.18. The HRD detected by genomic assays and residual tumor at primary surgery and stage was correlated with progression-free survival at multivariate analysis. Conclusions Results suggest the feasibility of academic tests for assessing HRD status that show robust concordance with Myriad and correlation with clinical outcome. The contribution of the functional information related to the RAD51 foci test to the genomic data needs further investigation. This work was supported by funding from the AIRC [grant numbers IG 2016 – ID. 18921 and IG 2021 – ID. 25932 projects – P.I. SP and CO-2018-12367051 (Ministero della Salute) P.I SP]; Ricerca Corrente grant M2/7 from Ministero della Salute to DC, Ricerca Corrente from Ministero della Salute to SP. SM is supported by the Italian Association for Cancer Research [grant number IG-2017 n: IG19997]. MITO16A/MaNGO-OV2 trial was partially supported by Roche. AL is a recipient of a grant from the Asociación Española contra el Cáncer (AECC) [grant number INVES20095LLOP]. VS is a recipient of a grant from the Instituto de Salud Carlos III [grant number CPII19/00033] and a European grant for personalized medicine [grant number ERAPERMED 2019-215]. BP is a recipient of a grant from GOIRC. BP was supported by ESMO with a Clinical Translational Fellowship aid supported by Roche. Any views, opinions, findings, conclusions, or recommendations expressed in this material are those solely of the authors and do not necessarily reflect those of ESMO or Roche. NC has received funding from AstraZeneca (to the institution). FP has received funding from Roche, AstraZeneca, Pfizer, Merck Sharp & Dome, Bayer, Incyte, Taiho Oncology, Janssen Cilag, Exelixis, Aileron, and Daiichi Sankyo (grants to the institution for clinical trial activities).
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- 2022
6. The Prognostic Value of the Circulating-Tumor DNA in High-Grade Serous Epithelial Ovarian Cancer: Experience From MITO-16a/MANGO-OV2a/ Clinical Trial
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Paracchini, L., Arenare, L., Scambia, G., Pisano, C., Ferrero, A., Chiodini, P., Califano, D., Pignata, S., D'Incalci, M., and Marchini, S.
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- 2023
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7. A Potential Pathogenetic Mechanism for Multiple Endocrine Neoplasia Type 2 Syndromes Involves ret-Induced Impairment of Terminal Differentiation of Neuroepithelial Cells
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Califano, D., D'Alessio, A., Colucci-D'Amato, G. L., De Vita, G., Monaco, C., Santelli, G., Di Fiore, P. P., Vecchio, G., Fusco, A., Santoro, M., and De Franciscis, V.
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- 1996
8. Effect of trail pheromones and weather on the moving behaviour of the army ant Eciton burchellii
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Califano, D. and Chaves-Campos, J.
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- 2011
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9. The Tyrosine Phosphatase Shp-2 Mediates Intracellular Signaling Initiated by Ret Mutants
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D’Alessio, A, Califano, D, Incoronato, M, Santelli, G, Florio, T, Schettini, G, Carlomagno, M S., Cerchia, L, and de Franciscis, V
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- 2003
10. The ASI P-Band Helicopter-Borne Integrated Sounder-Sar System: Preliminary Results of The 2018 Morocco Desert Campaign
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Perna, S., primary, Facchinetti, C., additional, Formaro, R., additional, Gennarelli, G., additional, Gerekos, C., additional, Lanari, R., additional, Longo, F., additional, Ludeno, G., additional, d'Alessandro, M. Mariotti, additional, Natale, A., additional, Noviello, C., additional, Alberti, G., additional, Palmese, G., additional, Papa, C., additional, Pica, G., additional, Rocca, F., additional, Salzillo, G., additional, Soldovieri, F., additional, Tebaldini, S., additional, Thakur, S., additional, Berardino, P., additional, Bruzzone, L., additional, Califano, D., additional, Catapano, I., additional, Ciofaniello, L., additional, Donini, E., additional, and Esposito, C., additional
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- 2019
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11. An improved airborne VHF radar sounder for ice and desert exploration
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Gennarelli, G., primary, Ludeno, G., additional, Catapano, I., additional, Soldovieri, F., additional, Alberti, G., additional, Califano, D., additional, Ciofaniello, L., additional, Palmese, G., additional, Papa, C., additional, Pica, G., additional, Salzillo, G., additional, Facchinetti, C., additional, and Longo, F., additional
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- 2018
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12. IFN-γ increases susceptibility to influenza A infection through suppression of group II innate lymphoid cells
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Califano, D, primary, Furuya, Y, additional, Roberts, S, additional, Avram, D, additional, McKenzie, A N J, additional, and Metzger, D W, additional
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- 2018
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13. Lipase biofilm deposited by Matrix Assisted Pulsed Laser Evaporation technique
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Antonio Aronne a, Francesco Bloisi b, c, Raffaela Calabria d, Valeria Califano d, Laura E. Depero e, Esther Fanelli a, Stefania Federici e, Patrizio Massoli d, Luciano R.M. Vicari b, Aronne, Antonio, Bloisi, Francesco, Raffaela, Calabria, Valeria, Califano, Laura E., Depero, Fanelli, Esther, Stefania, Federici, Patrizio, Massoli, and Vicari, LUCIANO ROSARIO MARIA
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Materials science ,Immobilized enzyme ,MAPLE ,Analytical chemistry ,General Physics and Astronomy ,engineering.material ,biosensor ,Pulsed laser deposition ,Matrix (chemical analysis) ,Enzyme immobilization ,Deposition (phase transition) ,Lipase ,Lypase ,Maple ,biology ,Substrate (chemistry) ,Surfaces and Interfaces ,General Chemistry ,Condensed Matter Physics ,Evaporation (deposition) ,Surfaces, Coatings and Films ,Biosensors ,Chemical engineering ,biology.protein ,engineering ,Biodiesel - Abstract
Lipase is an enzyme that finds application in biodiesel production and for detection of esters and triglycerides in biosensors. Matrix Assisted Pulsed Laser Evaporation (MAPLE), a technique derived from Pulsed Laser Deposition (PLD) for deposition of undamaged biomolecules or polymers, is characterized by the use of a frozen target obtained from a solution/suspension of the guest material (to be deposited) in a volatile matrix (solvent). The presence of the solvent avoids or at least reduces the potential damage of guest molecules by laser radiation but only the guest material reaches the substrate in an essentially solvent-free deposition. MAPLE can be used for enzymes immobilization, essential for industrial application, allowing the development of continuous processes, an easier separation of products, the reuse of the catalyst and, in some cases, enhancing enzyme properties (pH, temperature stability, etc.) and catalytic activity in non-aqueous media. Here we show that MAPLE technique can be used to deposit undamaged lipase and that the complex structure (due to droplets generated during extraction from target) of the deposited material can be controlled by changing the laser beam fluence.
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- 2015
14. Interferometric experiments with the first Italian airborne P-band radar
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Fornaro, G., primary, Tebaldini, S., additional, Perna, S., additional, Mariotti d'Alessandro, M., additional, Berardino, P., additional, Lanari, R., additional, Manzo, M., additional, Rocca, F., additional, Soldovieri, F., additional, Alberti, G., additional, Papa, C., additional, Salzillo, G., additional, Pica, G., additional, Palmese, G., additional, Califano, D., additional, Ciofaniello, L., additional, Longo, F., additional, Facchinetti, C., additional, and Formaro, R., additional
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- 2016
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15. Complex regulation of the cyclin-dependent kinase inhibitor p27kip1 in thyroid cancer cells by the PI3K/AKT pathway: regulation of p27kip1 expression and localization
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Motti, M. L., Califano, D., Troncone, G., Marco, C., Migliaccio, I., Palmieri, E., Pezzullo, L., Palombini, L., Alfredo Fusco, Viglietto, G., Motti, Ml, Califano, D, Troncone, Giancarlo, DE MARCO, C, Migliaccio, I, Palmieri, E, Pezzullo, L, Palombini, Lucio, Fusco, Alfredo, and Viglietto, G.
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Cytoplasm ,Time Factors ,Morpholines ,Blotting, Western ,Cell Cycle Proteins ,Protein Serine-Threonine Kinases ,Transfection ,Phosphatidylinositol 3-Kinases ,Cytosol ,Cell Line, Tumor ,Proto-Oncogene Proteins ,Humans ,Thyroid Neoplasms ,Phosphorylation ,S-Phase Kinase-Associated Proteins ,Reverse Transcriptase Polymerase Chain Reaction ,Tumor Suppressor Proteins ,PTEN Phosphohydrolase ,Flow Cytometry ,Phosphoric Monoester Hydrolases ,Androstadienes ,Enzyme Activation ,Gene Expression Regulation, Neoplastic ,Original Research Paper ,Bromodeoxyuridine ,Microscopy, Fluorescence ,Chromones ,Wortmannin ,Proto-Oncogene Proteins c-akt ,Cyclin-Dependent Kinase Inhibitor p27 - Abstract
Functional inactivation of the tumor suppressor p27(kip1) in human cancer occurs either through loss of expression or through phosphorylation-dependent cytoplasmic sequestration. Here we demonstrate that dysregulation of the PI3K/AKT pathway is important in thyroid carcinogenesis and that p27(kip1) is a key target of the growth-regulatory activity exerted by this pathway in thyroid cancer cells. Using specific PI3K inhibitors (LY294002, wortmannin, and PTEN) and a dominant active AKT construct (myrAKT), we demonstrated that the PI3K/AKT pathway controlled thyroid cell proliferation by regulating the expression and subcellular localization of p27. Results obtained with phospho-specific antibodies and with transfection of nonphosphorylable p27(kip1) mutant constructs demonstrated that PI3K/AKT-dependent regulation of p27(kip1) mislocalization in thyroid cancer cells occurred via phosphorylation of p27(kip1) at T157 and T198 (but not at S10 or T187). Finally, we evaluated whether these results were applicable to human tumors. Analysis of 100 thyroid carcinomas indicated that p27(kip1) phosphorylation at T157/T198 and cytoplasmic mislocalization were preferentially associated with activation of the PI3K/AKT pathway. Thus the PI3/AKT pathway and its effector p27(kip1) play major roles in thyroid carcinogenesis.
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- 2005
16. Signaling through ras is essential for ret oncogene induced cell differentiation in PC12 cells
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CALIFANO D., D'ALESSIO A., COLUCCI D'AMATO G. L., CALÌ G., CANNADA BARTOLI P., SANTELLI G., DE FRANCISCIS V., RIZZO, CLAUDIA, VECCHIO, GIANCARLO, Califano, D., Rizzo, Claudia, D'Alessio, A., COLUCCI D'AMATO, G. L., Calì, G., CANNADA BARTOLI, P., Santelli, G., Vecchio, Giancarlo, and DE FRANCISCIS, V.
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- 2000
17. miR-191 Down-Regulation Plays a Role in Thyroid Follicular Tumors through CDK6 Targeting
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Colamaio M, Borbone E, Russo L, Bianco M, Federico A, Califano D, Chiappetta G, Pallante P, Troncone G, Battista S, and Fusco A.
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endocrine system ,miR-1 expression ,endocrine system diseases ,thyroid neoplasias - Abstract
Context:Well-differentiated thyroid carcinomas include papillary (PTC) and follicular (FTC) carcinomas. FTC is usually a more aggressive form of cancer than the more common papillary type. miR-191 expression is frequently altered in several neoplasias, being up-regulated in some cases, such as pancreatic carcinomas, and down-regulated in other carcinomas, such as melanomas.Objective:The objective was to evaluate the expression and the role of miR-191 in thyroid carcinogenesis.Design:The expression of miR-191 was analyzed in tissues from patients with follicular adenoma (n = 24), FTC (n = 24), PTC (n = 15), anaplastic thyroid carcinoma (n = 8), and the follicular variant of PTC (n = 6) compared with normal thyroid tissues by quantitative RT-PCR. miR-191 expression was restored in the follicular thyroid cell line WRO, and the effects on cell proliferation, migration, and target expression were evaluated.Results:miR-191 is down-regulated in follicular adenoma, FTC, and follicular variant of PTC. We identified CDK6, a serine-threonine kinase involved in the control of cell cycle progression, as a novel target of miR-191. Restoration of miR-191 expression in WRO cells reduces cell growth and migration rate on vitronectin. CDK6 overexpression, correlated with miR-191 down-regulation, was found in follicular adenoma and FTC, suggesting a role of miR-191 down-regulation in the generation of these neoplasias.Conclusions:Our results suggest that miR-191 down-regulation plays a role in thyroid neoplasias of the follicular histotype, likely by targeting CDK6.
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- 2011
18. Echo Simulator Systems for Exomars 2016 Radar Doppler Altimeters tests
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Cirillo, G., primary, Gagliardi, M., additional, Palmese, G., additional, Califano, D., additional, Ciofaniello, L., additional, Laiso, R. D., additional, Bortone, M., additional, Santovito, M. R., additional, Alberti, G., additional, Mattei, S., additional, and Pepe, P., additional
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- 2015
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19. Phenol derived CVFM analogs inhibitors of ras farnesyl transferase possessing cellular in vitro activity
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CALIENDO, GIUSEPPE, FIORINO, FERDINANDO, GRIECO, PAOLO, PERISSUTTI, ELISA, RAMUNNO, ANNA, SANTAGADA, VINCENZO, ALBRIZIO, STEFANIA, CALIFANO D., GIULIANO A., SANTELLI G., Caliendo, Giuseppe, Fiorino, Ferdinando, Grieco, Paolo, Perissutti, Elisa, Ramunno, Anna, Santagada, Vincenzo, Albrizio, Stefania, Califano, D., Giuliano, A., and Santelli, G.
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phenol-derived peptide ,Structure-activity relationship ,antitumor agents - Abstract
A study was performed on structure-activity relationships of a series of phenol-derived CVFM analogs as inhibitors of ras Farnesyltransferase (FTase). The effect of various substituents on the phenol ring was examd., while the VFM moiety of the potent inhibitor CVFM was kept const. The FTase inhibitory activity, reported as IC50, was influenced by both the chem. properties and the relative position of the substituents on the phenolic ring. The most active compds. in this series contained a chloro or bromine substituent on the phenolic ring. Subsequently the authors have tested the effects of these FTase inhibitors on the anchorage-dependent growth of two rat epithelial cell lines, FRTL-5 and the same line v-Ha-ras transformed. While most of the compds. were inactive, two showed a growth inhibitory effect: I was active against normal as well against transformed cells while II was active only against transformed cells.
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- 1998
20. Overexpression of the HIP gene coding for a heparin/heparan sulfate-binding protein in human thyroid carcinomas
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de Nigris F, Visconti R, Cerutti J, Califano D, Mineo A, Santoro M, Santelli G, Fusco A, de NIGRIS, Filomena, Visconti, R, Cerutti, J, Califano, D, Mineo, A, Santoro, M, Santelli, G, Fusco, A., F. d., Nigri, R., Visconti, J., Cerutti, D., Califano, A., Mineo, Santoro, Massimo, G., Santelli, and Fusco, Alfredo
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Heparin ,metabolism, Carrier Protein ,Carcinoma ,Papillary ,Thyroid Gland ,metabolism, Thyroid Neoplasm ,metabolism, Humans, Thyroid Gland ,metabolism, Tumor Cell ,Carcinoma, Papillary ,Up-Regulation ,genetics, Gene Expression Regulation ,Gene Expression Regulation, Neoplastic ,Neoplastic, Heparin ,metabolism, Heparitin Sulfate ,Cultured, Up-Regulation ,Tumor Cells, Cultured ,Humans ,Heparitin Sulfate ,Thyroid Neoplasms ,Carrier Proteins - Abstract
A subtractive library screening was performed to identify changes in gene expression that occur during the process of neoplastic transformation of thyroid cells. A cDNA library was constructed from a human thyroid papillary carcinoma cell line (NPA) subtracted with cDNAs from normal thyroid cells (HTC 2). The differential screening of this library lead to the isolation of 39 cDNA clones; six of them showed homology with a recently isolated gene, named HIP, that codes for a protein belonging to a novel class of heparin/heparan sulfate-binding proteins. Northern blot analysis revealed HIP gene overexpression in all of the human thyroid carcinoma cell lines analyzed, as compared to the HTC 2 cells. HIP expression was particularly abundant in the anaplastic carcinoma-derived cell lines. The analysis of surgically removed thyroid tumors showed overexpression of HIP gene in all of the carcinomas, independent of the histotype, although the largest increase in HIP expression was observed in the undifferentiated forms. In contrast, none of the benign adenomas or normal thyroid tissues showed HIP overexpression. To establish the role of HIP overexpression in cell transformation, the NPA cell line was transfected with an eukaryotic expression vector carrying the HIP gene in the antisense orientation. Stable transfectants expressed reduced HIP mRNA levels and showed morphological changes, such as becoming spindle-shaped and growing scattered. The growth rate of the antisense clones was greatly reduced compared to the NPA cells transfected with the backbone vector. Taken together, these results indicate that HIP gene overexpression is associated with thyroid carcinogenesis and strongly suggest its involvement in thyroid cell growth regulation.
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- 1998
21. Akt-dependent T198 phosphorylation of cicli-dependent kinase inhibitor p27kip1 in breast cancer
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Motti ML, De Marco C, Califano D, Fusco A, and Viglietto G.
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- 2004
22. Secondary Instabilities in Two-Dimensional Collisionless Magnetic Field Line Reconnection in a Fluid Plasma
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Pegoraro, Francesco and Califano, D. DEL S. A. R. T. O. F.
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- 2004
23. Thyroid specific expression of the Ki-ras oncogene in transgenic mice
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Santelli G., de Franciscis V., Chiappetta G., D'Alessio A., Califano D., Mineo A., Monaco C., VECCHIO, GIANCARLO, V Zappia, M Salvatore ,F Ragione, Santelli, G., de Franciscis, V., Chiappetta, G., D'Alessio, A., Califano, D., Mineo, A., Monaco, C., and Vecchio, Giancarlo
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- 1993
24. Design and Validation of a Multimode Multifrequency VHF/UHF Airborne Radar
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Papa, C., primary, Alberti, G., additional, Salzillo, G., additional, Palmese, G., additional, Califano, D., additional, Ciofaniello, L., additional, Daniele, M., additional, Facchinetti, C., additional, Longo, F., additional, Formaro, R., additional, Catapano, I., additional, Crocco, L., additional, Gennarelli, G., additional, and Soldovieri, F., additional
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- 2014
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25. The Tyrosine Phosphatase Shp-2 Mediates Intracellular Signaling Initiated by Ret Mutants
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D?ALESSIO A. 1, CALIFANO D 1., INCORONATO M 2., SANTELLI G. 1, FLORIO T. 3-4, SCHETTINI G. 3-4, CARLOMAGNO M.S. 2, and CERCHIA L. 5 AND DE FRANCISCIS V. 5
- Abstract
The Src homology 2-containing tyrosine phosphatase, Shp-2, is a crucial enzyme that mediates intracellular signaling and is implicated in cell proliferation and differentiation. Here we investigated the involvement of the Shp-2 tyrosine phosphatase in determining the downstream signaling pathways initiated by the Ret oncogene, carrying either the cysteine 634 to tyrosine or the methionine 918 to threonine substitutions. These mutations convert the receptor tyrosine kinase, Ret, into a dominant transforming protein and induce constitutive activation of its intrinsic tyrosine kinase activity leading to congenital and sporadic cancers in neuroendocrine organs. Using the PC12, rat pheochromocytoma cell line, as model system, we show that Shp-2 mediates immediate-early gene expression if induced by either of the mutant alleles. Furthermore, we show that Shp-2 activity is required for RetM918Tinduced Akt activation. The results indicate that Shp-2 is a downstream mediator of the mutated receptors RetC634Y and RetM918T, thus suggesting that it may act as a limiting factor in Ret-associated endocrine tumors, in the neoplastic syndromes multiple endocrine neoplasia types 2A and 2B.
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- 2003
26. Effect of trail pheromones and weather on the moving behaviour of the army ant Eciton burchellii
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Califano, D., primary and Chaves-Campos, J., additional
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- 2010
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27. 99 mTc red blood cells scintigraphy in pediatric cutaneous vascular lesions of maxillo-facial area
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Fiore, F., Califano, L., Cortese, Antonio, Califano, D., and Mansi, L.
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- 1990
28. Erratum: Isolation of a SIR-like gene, SIR-T8, that is overexpressed in thyroid carcinoma cell lines and tissues
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de Nigris, F, primary, Cerutti, J, additional, Morelli, C, additional, Califano, D, additional, Chiariotti, L, additional, Viglietto, G, additional, Santelli, G, additional, and Fusco, A, additional
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- 2002
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29. Isolation of a SIR-like gene, SIR-T8, that is overexpressed in thyroid carcinoma cell lines and tissues
- Author
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de Nigris, F, primary, Cerutti, J, additional, Morelli, C, additional, Califano, D, additional, Chiariotti, L, additional, Viglietto, G, additional, Santelli, G, additional, and Fusco, A, additional
- Published
- 2002
- Full Text
- View/download PDF
30. Regulation of thymosin beta10 expression by TSH and other mitogenic signals in the thyroid gland and in cultured thyrocytes
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Viglietto, G, primary, Califano, D, additional, Bruni, P, additional, Baldassarre, G, additional, Vento, MT, additional, Belletti, B, additional, Fedele, M, additional, Santelli, G, additional, Boccia, A, additional, Manzo, G, additional, Santoro, M, additional, and Fusco, A, additional
- Published
- 1999
- Full Text
- View/download PDF
31. ChemInform Abstract: Phenol‐Derived CVFM Analogue Inhibitors of Ras Farnesyltransferase Possessing Cellular in vitro Activity.
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CALIENDO, G., primary, FIORINO, F., additional, GRIECO, P., additional, PERISSUTTI, E., additional, RAMUNNO, A., additional, SANTAGADA, V., additional, ALBRIZIO, S., additional, CALIFANO, D., additional, GIULIANO, A., additional, and SANTELLI, G., additional
- Published
- 1999
- Full Text
- View/download PDF
32. Transforming potential of dail oncogene in transgenic mice
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Monaco, C., primary, Califano, D., additional, D'Alessio, A., additional, Chiappetta, G., additional, Palmieri, G., additional, Casamassini, A., additional, Colucci-D'Amato, L., additional, Santelli, G., additional, Mineo, A., additional, Manzo, G., additional, D'Urso, M., additional, de Franciscis, V., additional, and Vecchio, G., additional
- Published
- 1994
- Full Text
- View/download PDF
33. Effects of the activated Ki-ras expression on thyroid epithelial cells in vivo and in vitro
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Califano, D., primary, Santelli, G., additional, de Franciscis, V., additional, Chiappetta, G., additional, Monaco, C., additional, D'Alessio, A., additional, Mineo, A., additional, Manzo, G., additional, and Vecchio, G., additional
- Published
- 1994
- Full Text
- View/download PDF
34. Synthesis and Cytotoxic Evaluation of Novel Spirohydantoin Derivatives of the Dihydrothieno[2,3-b]naphtho-4,9-dione System
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Gomez-Monterrey, I., Santelli, G., Campiglia, P., Califano, D., Falasconi, F., Pisano, C., Vesci, L., Lama, T., Grieco, P., and Novellino, E.
- Abstract
The synthesis and cytotoxic evaluation of 3-(alkyl)(alkyl-substituted)spiro[(dihydroimidazo-2,4-dione)-5,3-(2,3-dihydrothieno[2,3-b]naphtho-4,9-dione)]derivatives are described. Evaluation of these analogues against the MCF-7 human breast carcinoma and SW 620 human colon carcinoma cell lines uncovered for most of the compounds a cytotoxic potency comparable to or greater than that of doxorubicin. Compound
15 exhibited remarkable cytotoxic activity against several other human solid tumor cell lines. Interestingly, only a partial cross-resistance to compound15 in selected tumor cell sublines known to be resistant to doxorubicin (MCF-7/Dx and A2780/Dx) was observed, whereas a total absence of cross-resistance in a tumor cell subline selected for resistance to cisplatin was found (A2780/DDP).- Published
- 2005
35. Human dbl proto-oncogene in 85 kb of Xq26, and determination of the transcription initiation site
- Author
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Palmieri, G., Franciscis, V. de, Casamassimi, A., Romano, G., Torino, A., Pingitore, P., Califano, D., Santelli, G., Eva, A., and Vecchio, G.
- Published
- 2000
- Full Text
- View/download PDF
36. Synthesis and biological activity of pseudopeptides inhibitors of Ras farnesyl transferase containing unconventional amino acids
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Caliendo, G., Fiorino, F., Grieco, P., Perissutti, E., Luca, S. De, Giuliano, A., Santelli, G., Califano, D., Severino, B., and Santagada, V.
- Published
- 1999
- Full Text
- View/download PDF
37. Phenol-derived CVFM analog inhibitors of Ras Farnesyltransferase possessing cellular in vitro activity
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Caliendo, G., Fiorino, E., Grieco, P., Perissutti, E., Ramunno, A., Santagada, V., Albrizio, S., Califano, D., Giuliano, A., and Santelli, G.
- Published
- 1998
- Full Text
- View/download PDF
38. Ligand stimulation of a Ret chimeric receptor carrying the activating mutation responsible for the multiple endocrine neoplasia type 2B.
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Rizzo, C, Califano, D, Colucci-D'Amato, G L, De Vita, G, D'Alessio, A, Dathan, N A, Fusco, A, Monaco, C, Santelli, G, Vecchio, G, Santoro, M, and de Franciscis, V
- Abstract
Inherited activating mutations of Ret, a receptor tyrosine kinase, predispose to multiple endocrine neoplasia (MEN) types 2A and 2B and familial medullary thyroid carcinoma. To investigate the effects induced by acute stimulation of Ret, we transfected both PC12 and NIH 3T3 cells with a molecular construct in which the ligand-binding domain of the epidermal growth factor receptor was fused to the catalytic domain of Ret. Acute stimulation of the chimeric receptor induced PC12 cells to express a neuronal-like phenotype. Moreover, we introduced the dominant mutation, responsible for the multiple endocrine neoplasia type 2B, in the catalytic domain of the Ret chimera. Expression of the mutant chimera, in the absence of ligand stimulation, induces the PC12 cells to acquire a flat morphology with short neuritic processes and transforms the NIH 3T3 cells. Stimulation of the mutant chimera with epidermal growth factor causes a drastic overgrowth of long neuritic processes, with the induction of the suc1-associated protein tyrosine phosphorylation in PC12 cells and higher transforming efficiency in NIH 3T3 cells. These data indicate that the gain-of-function MEN2B mutation does not abrogate ligand responsiveness of Ret and suggest that the presence of Ret ligand could play a role in the pathogenesis of the MEN2B syndrome.
- Published
- 1996
39. Production of Transgenic Mice Expressing the Ki-ras Oncogene under the Control of a Thyroglobulin Promoter
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Santelli, G., Franciscis, V. D., Giuseppe PORTELLA, Chiappetta, G., D Alessio, A., Califano, D., Rosati, R., Mineo, A., Monaco, C., Manzo, G., Pozzi, L., Vecchio, G., Santelli, G., DE FRANCISCIS, V., Portella, Giuseppe, Chiappetta, G., D' ALESSIO, A., Califano, D., Rosati, R., Mineo, A., Monaco, C., Manzo, G., Pozzi, L., and Vecchio, Giancarlo
- Subjects
ACTIVATION ,HIGH-FREQUENCY ,CARCINOMAS ,CHLORAMPHENICOL ACETYLTRANSFERASE ,PAPILLARY ,GENE ,TISSUE-SPECIFIC EXPRESSION ,TRANSFORMATION ,THYROID EPITHELIAL-CELLS ,SARCOMA-VIRUS - Abstract
Transgenic mice have been generated bearing three fusion genes consisting of (a) a 900-base pair rat thyroglobulin promoter followed by a gene coding for a chloroamphenicol acetyl transferase activity; (b) the same promoter followed by the complementary DNA of the human activated Ki-ras oncogene; (c) a 2000-base pair rat thyroglobulin promoter followed by the complementary DNA of the human activated Ki-ras. We have shown that the 900-base pair rat thyroglobulin promoter is able to direct the expression of the reporter gene specifically in the thyroid gland of transgenic mice. The mice bearing the two Ki-ras constructs, which express the transgene in thyroid glands, show thyroid abnormalities, although at very low incidence. These lesions appear after a long latency and with a benign aspect, thus suggesting that, in agreement with literature data on naturally occurring human thyroid tumors, the action of an activated ras gene is not sufficient to attain a complete malignant conversion of thyroid glands in vivo. However, ras expression in thyroid follicular cells represents a favorable ground for tumor development, as shown by the fact that goitrogen stimulation experiments increase the occurrence of tumors.
40. High HMGA2 expression and high body mass index negatively affect the prognosis of patients with ovarian cancer
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Califano, D., Pignata, S., Losito, N. S., Ottaiano, A., Greggi, S., Simone, V., Cecere, S., Aiello, C., Esposito, F., Alfredo Fusco, Chiappetta, G., Califano, D., Pignata, S., Losito, N. S., Ottaiano, A., Greggi, S., DE SIMONE, V., Cecere, S., Aiello, C., Esposito, F., Fusco, Alfredo, and Gennaro, G.
- Subjects
hmga2 - Abstract
HMGA2 is a small, non-histone, chromatin-associated protein with a key role in tumorigenesis and adipogenesis. Indeed, HMGA2 overexpression has been frequently detected in several malignant neoplasms and inhibition of its expression prevents thyroid cell transformation. Moreover, HMGA2 null mice show a pigmy phenotype with a great reduction in fat tissue. To investigate whether HMGA2 expression correlates with clinico-pathological parameters and patient outcome, immunohistochemical analysis of HMGA2 expression was performed in ovarian cancer specimens from 117 patients. HMGA2 overexpression was found in 39% of the cases and, interestingly, positively correlated with the Body Mass Index (BMI). Moreover, high BMI (>=25 kg/m2 ) and high HMGA2 expression/BMI combined evaluation predicted shorter disease free survival. High BMI (>=25 kg/m2 ), high expression of HMGA2 and high HMGA2 expression/BMI combined evaluation predicted shorter overall survival. In multivariate analysis, the concomitant high expression of HMGA2 and high BMI (>=25 kg/m2 ) was an independent prognostic factor. Finally, the Body Mass Index (>=25 kg/m2 ) negatively correlated with the patient response to chemotherapy (P = 0.039). Therefore, the data reported herein suggest that the combined evaluation of HMGA2 expression and obesity assessed through BMI, can be considered a marker of poor prognosis in patients affected by ovarian carcinoma. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.
41. Activated RET/PTC oncogene elicits immediate early and delayed response genes in PC12 cells
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Califano, D., Monaco, C., Vita, G., D Alessio, A., Dathan, N. A., Possenti, R., Vecchio, G., Alfredo Fusco, Santoro, M., Franciscis, V., Califano, D., Monaco, C., DE VITA, Gabriella, D'Alessio, A., Dathan, N. A., Possenti, R., Vecchio, Giancarlo, Fusco, Alfredo, Santoro, Massimo, and de Franciscis, V.
- Subjects
EXPRESSION ,congenital, hereditary, and neonatal diseases and abnormalities ,endocrine system ,PHEOCHROMOCYTOMA ,RET PROTO-ONCOGENE ,endocrine system diseases ,NEURON-SPECIFIC ENOLASE ,SIGNAL-TRANSDUCTION ,TYROSINE KINASE ,ONCOGENE ,Receptors, Nerve Growth Factor ,PC12 Cells ,MAMMALIAN-CELLS ,Proto-Oncogene Proteins ,Animals ,Drosophila Proteins ,Promoter Regions, Genetic ,neoplasms ,Genes, Immediate-Early ,Neurons ,VGF GENE ,NERVE GROWTH-FACTOR ,Proto-Oncogene Proteins c-ret ,Receptor Protein-Tyrosine Kinases ,PC12 ,Rats, Inbred F344 ,Rats ,PHEOCHROMOCYTOMA CELLS ,RET ,RAS ,Signal Transduction - Abstract
The expression of the receptor-like tyrosine kinase RET is associated with tumors, tissues or cell lines of neural crest origin. In addition RET products (Ret) are involved in determining cell fate during the differentiation of the enteric nervous system and during renal organogenesis. However, as yet, no direct evidence exists to indicate that the Ret kinase activity might interfere in a specific way with cellular differentiation, or proliferation, of a neural crest derived cell line. By using two constitutively activated forms of RET (RET/PTC1 and RET/PTC3) in transient transfection experiments, we have obtained evidence that active RET could reprogramme the gene expression pattern in the rat pheochromocytoma PC12 cell line. Transcription driven by gene promoters, such as NGFI-A and vgf, which belong, respectively, to primary and delayed response genes to nerve growth factor (NGF), and by the neuron-specific enolase (NSE) promoter, is rapidly induced by the expression of activated RET oncogenes. This induction is not elicited in other non neural derived cell types tested. We also demonstrate that endogenous ras activity is required for RET induction of these neural markers. Finally, in the RET/PTC transfected PC12 cells, NGF is unable to induce further their transcription. This suggests that RET/PTC could share an intracellular signalling pathway with the NGF-receptor.
42. Thymosin beta-10 gene expression as a possible tool in diagnosis of thyroid neoplasias
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Chiappetta, G., Francesca Pentimalli, Monaco, M., Fedele, M., Pasquinelli, R., Pierantoni, Gm, Ribecco, Mt, Santelli, G., Califano, D., Pezzullo, L., Fusco, A., Chiappetta, G., Pentimalli, F., Monaco, M., Fedele, M., Pasquinelli, R., Pierantoni, GIOVANNA MARIA, Ribecco, M. T., Santelli, G., Califano, D., Pezzullo, L., and Fusco, Alfredo
- Subjects
Adenoma ,Thymosin ,Cell Movement ,Cell Line, Tumor ,Carcinoma ,Disease Progression ,Thyroid Gland ,Humans ,Thyroid Neoplasms ,Immunohistochemistry ,Cell Proliferation - Abstract
Overexpression of thymosin beta-10 (TB10) has been shown in rat thyroid transformed cell lines, and in human thyroid carcinoma tissues and cell lines. To investigate whether TB10 detection could be a valid tool in the diagnosis of human thyroid neoplasias, we extended the analysis of TB10 expression to a large number of thyroid hyperproliferative and neoplastic tissues using an immunohistochemical assay. Our analyses showed a TB10 positive staining in all human thyroid carcinomas particularly in the anaplastic histotypes, whereas no TB10 immunostaining was observed in normal thyroid, in adenomas and the majority of the goiters. These results suggest that the evaluation of TB10 gene expression may be considered a promising means of diagnosis of human thyroid hyperproliferative disorders.
43. Overexpression of the HIP gene coding for a heparin/heparan sulfate- binding protein in human thyroid carcinomas
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filomena de nigris, Visconti, R., Cerutti, J., Califano, D., Mineo, A., Santoro, M., Santelli, G., and Fusco, A.
44. A new airborne multi-mode and multi-band low frequency radar
- Author
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Alberti, G., Papa, C., Palmese, G., Salzillo, G., Ciofaniello, L., Califano, D., Daniele, M., Adirosi, D., francesco longo, Facchinetti, C., and Formaro, R.
45. Thymosin β-10 gene overexpression correlated with the highly malignant neoplastic phenotype of transformed thyroid cells in vivo and in vitro
- Author
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Califano, D., Monaco, C., Santelli, G., Giuliano, A., Veronese, M. L., Berlingieri, M. T., Franciscis, V., Berger, N., Trapasso, F., Santoro, M., Viglietto, G., and Alfredo Fusco
46. Biological Role of Tumor/Stromal CXCR4-CXCL12-CXCR7 in MITO16A/MaNGO-OV2 Advanced Ovarian Cancer Patients
- Author
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Crescenzo D’Alterio, Anna Spina, Laura Arenare, Paolo Chiodini, Maria Napolitano, Francesca Galdiero, Luigi Portella, Vittorio Simeon, Simona Signoriello, Francesco Raspagliesi, Domenica Lorusso, Carmela Pisano, Nicoletta Colombo, Gian Franco Zannoni, Nunzia Simona Losito, Rossella De Cecio, Giosuè Scognamiglio, Daniela Califano, Daniela Russo, Valentina Tuninetti, Maria Carmela Piccirillo, Piera Gargiulo, Francesco Perrone, Sandro Pignata, Stefania Scala, D'Alterio, C., Spina, A., Arenare, L., Chiodini, P., Napolitano, M., Galdiero, F., Portella, L., Simeon, V., Signoriello, S., Raspagliesi, F., Lorusso, D., Pisano, C., Colombo, N., Zannoni, G. F., Losito, N. S., De Cecio, R., Scognamiglio, G., Califano, D., Russo, D., Tuninetti, V., Piccirillo, M. C., Gargiulo, P., Perrone, F., Pignata, S., Scala, S., D'Alterio, C, Spina, A, Arenare, L, Chiodini, P, Napolitano, M, Galdiero, F, Portella, L, Simeon, V, Signoriello, S, Raspagliesi, F, Lorusso, D, Pisano, C, Colombo, N, Zannoni, G, Losito, N, De Cecio, R, Scognamiglio, G, Califano, D, Russo, D, Tuninetti, V, Piccirillo, M, Gargiulo, P, Perrone, F, Pignata, S, and Scala, S
- Subjects
Cancer Research ,CXCR4-CXCL12-CXCR7 axi ,ovarian cancer ,Oncology ,endocrine system diseases ,embryonic structures ,chemokine ,tumor microenvironment ,biological phenomena, cell phenomena, and immunity ,biological factors ,prognosi ,CXCR4-CXCL12-CXCR7 axis ,prognosis - Abstract
This study investigated the prognostic role of the CXCR4-CXCL12-CXCR7 axis in advanced epithelial ovarian cancer (EOC) patients receiving first-line treatment within the MITO16A/MaNGO-OV2 phase-IV trial. CXCR4-CXCL12-CXCR7 expression was evaluated in the epithelial and stromal component of 308 EOC IHC-stained tumor samples. The statistical analysis focused on biomarkers’ expression, their association with other variables and prognostic value. Zero-inflated tests, shrinkage, bootstrap procedures, and multivariable models were applied. The majority of EOC (75.0%) expressed CXCR4 and CXCR7, 56.5% expressed the entire CXCR4-CXCL12-CXCR7 axis, while only 4.6% were negative for CXCL12 and its cognate receptors, in regard to the epithelial component. Stromal CXCL12 and CXCR7, expressed in 11.2% and 65.5%, respectively, were associated with the FIGO stage. High CXCL12 in epithelial cancer cells was associated with shorter progression-free and overall survival. However, after adjusting for overfitting due to best cut-off multiplicity testing, the significance was lost. This is a wide-ranging, prospective study in which CXCR4-CXCL12-CXCR7 were systematically evaluated in epithelial and stromal components, in selected stage III-IV EOC. Although CXCL12 was not prognostic, epithelial expression identified high-risk FIGO stage III patients for PFS. These data suggest that it might be worth studying the CXCL12 axis as a therapeutic target to improve treatment efficacy in EOC patients.
- Published
- 2022
47. Thromboembolic events and antithrombotic prophylaxis in advanced ovarian cancer patients treated with bevacizumab: secondary analysis of the phase IV MITO-16A/MaNGO-OV2A trial
- Author
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Francesco Perrone, Ugo De Giorgi, Maria Carmela Piccirillo, Annamaria Ferrero, Andrea Lissoni, Mariateresa Lapresa, Laura Arenare, Giorgio Bogani, Nicoletta Colombo, Daniela Califano, Angiolo Gadducci, Enrico Breda, Raimondo Di Liello, Giovanni Scambia, Andrea De Censi, Gennaro Daniele, Piera Gargiulo, Sandro Pignata, Paolo Scollo, Ciro Gallo, Margherita Nardin, Saverio Cinieri, Rossella Lauria, Francesco Raspagliesi, Vanda Salutari, Simona Frezzini, Carmela Pisano, Stefano Greggi, Domenica Lorusso, G. Artioli, Mariagrazia Distefano, Sabrina Chiara Cecere, Dionyssios Katsaros, Germana Tognon, Clorinda Schettino, Di Liello, R, Arenare, L, Raspagliesi, F, Scambia, G, Pisano, C, Colombo, N, Frezzini, S, Tognon, G, Artioli, G, Gadducci, A, Lauria, R, Ferrero, A, Cinieri, S, De Censi, A, Breda, E, Scollo, P, De Giorgi, U, Lissoni, A, Katsaros, D, Lorusso, D, Salutari, V, Cecere, S, Lapresa, M, Nardin, M, Bogani, G, Distefano, M, Greggi, S, Gargiulo, P, Schettino, C, Gallo, C, Daniele, G, Califano, D, Perrone, F, Pignata, S, Piccirillo, M, Di Liello, R., Arenare, L., Raspagliesi, F., Scambia, G., Pisano, C., Colombo, N., Frezzini, S., Tognon, G., Artioli, G., Gadducci, A., Lauria, R., Ferrero, A., Cinieri, S., De Censi, A., Breda, E., Scollo, P., De Giorgi, U., Lissoni, A. A., Katsaros, D., Lorusso, D., Salutari, V., Cecere, S. C., Lapresa, M., Nardin, M., Bogani, G., Distefano, M., Greggi, S., Gargiulo, P., Schettino, C., Gallo, C., Daniele, G., Califano, D., Perrone, F., Pignata, S., and Piccirillo, M. C.
- Subjects
medicine.medical_specialty ,Bevacizumab ,medicine.drug_class ,medicine.medical_treatment ,venous thromboembolism ,ovarian cancer ,Carcinoma, Ovarian Epithelial ,Antineoplastic Agents, Immunological ,Fibrinolytic Agents ,Secondary analysis ,Internal medicine ,Thromboembolism ,Antithrombotic ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Cumulative incidence ,Aged ,Ovarian Neoplasms ,Chemotherapy ,business.industry ,Incidence (epidemiology) ,Anticoagulant ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,Oncology ,Female ,Ovarian cancer ,business ,medicine.drug - Abstract
IntroductionThe use of routine antithrombotic prophylaxis is not recommended for advanced cancer patients receiving chemotherapy. The effect of bevacizumab-containing therapy on the risk of thromboembolic events remains controversial in ovarian cancer patients. We report on the incidence of thromboembolic events and the prevalence of antithrombotic therapy in patients enrolled in the single arm, phase IV, MITO-16A/MaNGO-OV2A trial.MethodsIn this trial, potential prognostic factors for patients with previously untreated ovarian cancer receiving a combination of platinum-based chemotherapy and bevacizumab were explored and the final analysis has already been reported. In this secondary analysis, the occurrence of thromboembolic events and the use of antithrombotic therapy were described according to the clinical characteristics of the patients. The prognostic role of thromboembolic events for progression-free and overall survival were also evaluated.ResultsFrom October 2012 to November 2014, 398 eligible patients were enrolled. 76 patients (19.1%) were receiving some type of anticoagulant or anti-aggregant treatment at baseline. Overall, 24 thromboembolic events were reported (cumulative incidence of 6.0%). The occurrence of thromboembolic events was not associated with baseline patient characteristics and was not modified by the use of antithrombotic prophylaxis (HR 0.60, 95% CI 0.18 to 2.0). Occurrence of thromboembolic events was not associated with progression-free survival (HR 1.34, 95% CI 0.83 to 2.15) or overall survival (HR 0.78, 95% CI 0.37 to 1.61).ConclusionsIn our study, a 6.0% rate of thromboembolic events was reported during treatment with bevacizumab plus chemotherapy. Thromboembolic events were not associated with the clinical characteristics of the patients or with the use of antithrombotic prophylaxis, nor did they significantly affect the long-term prognosis.Trial registration numberNCT01706120
- Published
- 2021
48. Evaluation of angiogenesis-related genes as prognostic biomarkers of bevacizumab treated ovarian cancer patients: Results from the phase iv mito16a/mango ov-2 translational study
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Gustavo Baldassarre, Nicoletta Colombo, Eliana Bignotti, Vincenzo Canzonieri, Vittorio Simeon, Paolo Chiodini, Sabrina Chiara Cecere, Gian Luca Rampioni Vinciguerra, Daniela Califano, Maria Carmela Piccirillo, Francesca Citron, Giovanni Scambia, Daniela Russo, Marco Montella, Francesco Perrone, Gian Franco Zannoni, Anna Spina, Alessandra Ciucci, Germana Tognon, Clorinda Schettino, Laura Arenare, Nunzia Simona Losito, Michele Del Sesto, Rossella De Cecio, Sandro Pignata, Gabriella Ferrandina, Piera Gargiulo, Giosuè Scognamiglio, Daniela Gallo, Simona Signoriello, Califano, D, Gallo, D, Vinciguerra, G, De Cecio, R, Arenare, L, Signoriello, S, Russo, D, Ferrandina, G, Citron, F, Losito, N, Gargiulo, P, Simeon, V, Scambia, G, Cecere, S, Montella, M, Colombo, N, Tognon, G, Bignotti, E, Zannoni, G, Canzonieri, V, Ciucci, A, Spina, A, Scognamiglio, G, Del Sesto, M, Schettino, C, Piccirillo, M, Perrone, F, Chiodini, P, Pignata, S, Baldassarre, G, Califano, D., Gallo, D., Vinciguerra, G. L. R., De Cecio, R., Arenare, L., Signoriello, S., Russo, D., Ferrandina, G., Citron, F., Losito, N. S., Gargiulo, P., Simeon, V., Scambia, G., Cecere, S. C., Montella, M., Colombo, N., Tognon, G., Bignotti, E., Zannoni, G. F., Canzonieri, V., Ciucci, A., Spina, A., Scognamiglio, G., Del Sesto, M., Schettino, C., Piccirillo, M. C., Perrone, F., Chiodini, P., Pignata, S., and Baldassarre, G.
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Oncology ,Cancer Research ,medicine.medical_specialty ,Bevacizumab ,Angiogenesis ,medicine.medical_treatment ,Article ,law.invention ,Bevacizumab treatment ,MicroRNAs ,Ovarian cancer ,Vessel density ,Randomized controlled trial ,Maintenance therapy ,law ,Internal medicine ,Medicine ,RC254-282 ,Chemotherapy ,business.industry ,Hazard ratio ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,MicroRNA ,medicine.disease ,Angiogenesi ,Settore MED/40 - GINECOLOGIA E OSTETRICIA ,Biomarker (medicine) ,business ,medicine.drug - Abstract
Simple Summary The possibility to identify, with appropriate biomarkers, patients that might mostly benefit from any given treatment is the basis of personalized oncology. Cancer biomarkers should be properly identified and validated on a large number of patients possibly enrolled in dedicated clinical trials. Here, we report the first molecular results of the MITO16A-ManGo-OV2 phase IV trial that was specifically designed to identify prognostic biomarkers of survival in epithelial ovarian cancer patients treated in first line with carboplatin-paclitaxel plus Bevacizumab (NCT01706120), a treatment for which validated predictive or prognostic biomarkers are still lacking. With this work we propose not only novel possible biomarkers for Bevacizumab-treated patients but also a way through which they can be properly collected, analyzed and statistically evaluated in the frame of large multicenter clinical trials. Abstract Background. Epithelial ovarian cancer (EOC) is a rare, highly lethal disease. In a subset of high grade EOC patients, maintenance therapy with the antiangiogenic drug Bevacizumab (BEV) is a valuable option. To date, no validated predictive or prognostic biomarkers exist for selecting EOC patients that might benefit from BEV treatment. Methods. Immunohistochemistry and RT-qPCR evaluated the expression of seven angiogenesis-related proteins and of a twelve microRNAs angio-signature in EOC patients, treated in first line with chemotherapy plus BEV (MITO16A/ManGO OV-2 phase IV trial). Centralized statistical analyses assessed the associations between each biomarker, clinical prognostic factors and survival outcomes. Results. High miR-484 expression was associated with longer progression-free and overall survival. Notably, the combined expression of miR-484 and its target VEGFB identified a subset of patients that might mostly benefit from BEV treatment. No other significant correlations were found between the other analyzed biomarkers and patients’ survival. The application of a shrinkage procedure to adjust for over-fitting hazard ratio estimates reduced the association significance. Conclusions. The analysis of angiogenesis related biomarkers in EOC patients homogenously treated with BEV in first line provides novel insight in their prognostic value and suggests that some of them might merit to be tested as predictive markers of drug activity in dedicated randomized trials.
- Published
- 2021
49. Carboplatin and paclitaxel plus avelumab compared with carboplatin and paclitaxel in advanced or recurrent endometrial cancer (MITO END-3): a multicentre, open-label, randomised, controlled, phase 2 trial
- Author
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Sandro Pignata, Giovanni Scambia, Clorinda Schettino, Laura Arenare, Carmela Pisano, Davide Lombardi, Ugo De Giorgi, Claudia Andreetta, Saverio Cinieri, Carmine De Angelis, Domenico Priolo, Claudia Casanova, Marta Rosati, Filippo Greco, Elena Zafarana, Ilaria Schiavetto, Serafina Mammoliti, Sabrina Chiara Cecere, Vanda Salutari, Simona Scalone, Alberto Farolfi, Marilena Di Napoli, Domenica Lorusso, Piera Gargiulo, Daniela Califano, Daniela Russo, Anna Spina, Rossella De Cecio, Paolo Chiodini, Francesco Perrone, Valentina Accinno, Chiara Altavilla, Giovanna Antonelli, Grazia Artioli, Francesco Avola, Bonifacio Barbara, Valentina Barbato, Michele Bartoletti, Simona Bevilacqua, Roberto Bordonaro, Oriana Borghese, Gaetano Buonfanti, Floriana Camarda, Giuliana Canzanella, Vittoria Carbone, Maria Rita Carbone, Giulia Carlo Stella, Chiara Cassani, Fabrizio Castagna, Monica Cattaneo, Margherita Cinefra, Nicoletta Colombo, Serena Corsetti, Monia Dall'Agata, Maria D'Amico, Gennaro Daniele, Elvira De Marino, Giovanni De Matteis, Sabino De Placido, Gabriella Del Bene, Antonia Del Giudice, Francesca Del Monte, Michele Del Sesto, Maddalena Donini, Giuliana Drudi, Gianluca Falcone, Adolfo Favaretto, Giulia Ferrera, Manuela Florio, Valeria Forestieri, Maria Stella Gallo, Ciro Gallo, Francesca Garibaldi, Fabiana Gerevini, Viola Ghizzoni, Maria Olga Giganti, Anna Gimigliano, Elena Giudice, Nicoletta Gnocchi, Adriano Gravina, Stefano Greggi, Maria Laura Iaia, Annalisa Ilardi, Gelsomina Iovine, Gabriella Ippoliti, Giulia Irollo, Ilenia Isidori, Mariateresa Lapresa, Giuseppe Lavenia, Laura Longhitano, Bortot Lucia, Gabriella Luzi, Sara Mariano, Valentina Marino, Giovanna Marrapese, Marilena Martino, Roberta Matocci, Enrica Mazzoni, Daniela Mercuri, Maria Mirto, Giovanna Mollo, Abbondanza Montinaro, Marta Moscatelli, Anna Maria Mosconi, Lucia Musacchio, Nicoletta Nanni, Pamela Natalucci, Milena Sabrina Nicoloso, Michele Orditura, Gabriella Maria Parma, Rodolfo Passalacqua, Michela Pelone, Maria Teresa Perri, Bruno Perrucci, Alessandra Piancastelli, Maria Carmela Piccirillo, Antonio Piccolo, Stefania Rapisardi, Giorgia Ravaglia, Teresa Ribecco, Caterina Ricci, Marianna Roccio, Fiorella Romano, Daniela Sambataro, Alfonso Savio, Ada Sbriglia, Cono Scaffa, Concetta Sergi, Francesca Sgandurra, Roberto Sorio, Stefano Stabile, Gianna Tabaro, Margherita Tambaro, Stefano Tamberi, Angelica Tecchiato, Angela Maria Trujillo, Eleonora Zaccarelli, Pignata, S, Scambia, G, Schettino, C, Arenare, L, Pisano, C, Lombardi, D, De Giorgi, U, Andreetta, C, Cinieri, S, De Angelis, C, Priolo, D, Casanova, C, Rosati, M, Greco, F, Zafarana, E, Schiavetto, I, Mammoliti, S, Cecere, S, Salutari, V, Scalone, S, Farolfi, A, Di Napoli, M, Lorusso, D, Gargiulo, P, Califano, D, Russo, D, Spina, A, De Cecio, R, Chiodini, P, Perrone, F, Accinno, V, Altavilla, C, Antonelli, G, Artioli, G, Avola, F, Barbara, B, Barbato, V, Bartoletti, M, Bevilacqua, S, Bordonaro, R, Borghese, O, Buonfanti, G, Camarda, F, Canzanella, G, Carbone, V, Carbone, M, Carlo Stella, G, Cassani, C, Castagna, F, Cattaneo, M, Cinefra, M, Colombo, N, Corsetti, S, Dall'Agata, M, D'Amico, M, Daniele, G, De Marino, E, De Matteis, G, De Placido, S, Del Bene, G, Del Giudice, A, Del Monte, F, Del Sesto, M, Donini, M, Drudi, G, Falcone, G, Favaretto, A, Ferrera, G, Florio, M, Forestieri, V, Gallo, M, Gallo, C, Garibaldi, F, Gerevini, F, Ghizzoni, V, Giganti, M, Gimigliano, A, Giudice, E, Gnocchi, N, Gravina, A, Greggi, S, Iaia, M, Ilardi, A, Iovine, G, Ippoliti, G, Irollo, G, Isidori, I, Lapresa, M, Lavenia, G, Longhitano, L, Lucia, B, Luzi, G, Mariano, S, Marino, V, Marrapese, G, Martino, M, Matocci, R, Mazzoni, E, Mercuri, D, and Mirto, M
- Subjects
Oncology ,Carboplatin - Abstract
Background: Adding immunotherapy to first-line chemotherapy might improve outcomes for patients with advanced or recurrent endometrial cancer. We aimed to compare carboplatin and paclitaxel versus avelumab plus carboplatin and paclitaxel as first-line treatment with avelumab given concurrent to chemotherapy and as maintenance after the end of chemotherapy. Methods: MITO END-3 is an open-label, randomised, controlled, phase 2 trial conducted at 31 cancer institutes, hospitals, and universities in Italy. Eligible patients were aged 18 years or older with histologically confirmed advanced (FIGO stage III–IV) or recurrent endometrial cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and no previous systemic anticancer therapy as primary treatment for advanced or metastatic disease. Participants were randomly assigned (1:1) using a computerised minimisation procedure stratified by centre, histology, and stage at study entry, to either receive carboplatin (area under the curve [AUC] 5 mg/mL × min) and paclitaxel (175 mg/m2; standard group) intravenously every 3 weeks for six to eight cycles or avelumab (10 mg/kg intravenously) added to carboplatin and paclitaxel (experimental group) every 3 weeks and then every 2 weeks as a single maintenance treatment after the end of chemotherapy until disease progression or unacceptable toxicity. Patients, treating clinicians, and those assessing radiological examinations were not masked to study treatment. The primary endpoint was investigator-assessed progression-free survival, measured in the intention-to-treat (ITT) population. Patients who received at least one dose of study drug were included in the safety analysis. Experimental group superiority was tested with 80% power and one-tailed α 0·20. This trial is registered with ClinicalTrials.gov (NCT03503786) and EudraCT (2016–004403–31). Findings: From April 9, 2018, to May 13, 2021, 166 women were assessed for eligibility and 39 were excluded. 125 eligible patients were randomly assigned to receive carboplatin and paclitaxel (n=62) or avelumab plus carboplatin and paclitaxel (n=63) and included in the ITT population. The median follow-up was 23·3 months (IQR 13·2–29·6) and was similar between the two groups. 91 progression-free survival events were reported, with 49 events in 62 patients in the standard group and 42 events in 63 patients in the experimental group. The median progression-free survival was 9·9 months (95% CI 6·7–12·1) in the standard group and 9·6 months (7·2–17·7) in the experimental group (HR of progression or death 0·78 [60% CI 0·65–0·93]; one-tailed p=0·085). Serious adverse events were reported more frequently in the experimental group (24 vs seven events in the standard group); neutrophil count decrease was the most frequent grade 3–4 adverse event (19 [31%] of 61 patients in the experimental group vs 26 [43%] of 61 patients in the standard group). Two deaths occurred in the experimental group during treatment (one respiratory failure following severe myositis [possibly related to treatment] and one cardiac arrest [not related to treatment]). Interpretation: Adding avelumab to first-line chemotherapy deserves further testing in patients with advanced or recurrent endometrial cancer, although consideration of mismatch repair status is warranted.
- Published
- 2023
50. Olaparib beyond progression compared with platinum chemotherapy after secondary cytoreductive surgery in patients with recurrent ovarian cancer: phase III randomized, open-label MITO 35b study, a project of the MITO-MANGO groups
- Author
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Clorinda Schettino, Lucia Musacchio, Michele Bartoletti, Paolo Chiodini, Laura Arenare, Gustavo Baldassarre, Daniela Califano, Ettore Capoluongo, Maria Paola Costi, Maurizio D'Incalci, Sergio Marchini, Delia Mezzanzanica, Nicola Normanno, Stefania Scala, Stefano Greggi, Francesco Perrone, Sandro Pignata, Schettino, C., Musacchio, L., Bartoletti, M., Chiodini, P., Arenare, L., Baldassarre, G., Califano, D., Capoluongo, E., Costi, M. P., D'Incalci, M., Marchini, S., Mezzanzanica, D., Normanno, N., Scala, S., Greggi, S., Perrone, F., and Pignata, S.
- Subjects
Ovarian Neoplasms ,Mangifera ,BRCA1 protein ,BRCA2 protein ,ovarian cancer ,Adenosine Diphosphate ,Carcinoma, Ovarian Epithelial ,Cytoreduction Surgical Procedures ,Female ,Humans ,Neoplasm Recurrence, Local ,Phthalazines ,Piperazines ,Platinum ,Poly(ADP-ribose) Polymerase Inhibitors ,Ribose ,Antineoplastic Agents ,Carcinoma ,Obstetrics and Gynecology ,Neoplasm Recurrence ,Local ,Oncology ,Ovarian Epithelial - Abstract
BackgroundPoly (ADP-ribose) polymerase inhibitors have transformed the management landscape for patients with ovarian cancer, demonstrating remarkable improvements in progression-free survival and overall survival. Unfortunately, most relapses are due to an acquired mechanism of resistance to these agents. We hypothesize that secondary cytoreductive surgery, removing resistant clones, might help to overcome the development of resistance to poly (ADP-ribose) polymerase inhibitors, prolonging their therapeutic effect.Primary ObjectiveTo determine the efficacy of olaparib beyond progression compared with standard platinum-based chemotherapy in patients with recurrent ovarian cancer progressed during or after poly (ADP-ribose) polymerase inhibitor maintenance therapy after secondary cytoreductive surgery.Study HypothesisOlaparib administered beyond progression is more effective in increasing progression-free survival and progression-free survival 2 compared with second-line platinum-based chemotherapy in patients after secondary cytoreductive surgery.Trial DesignPhase III, randomized, open-label, multicenter trial. Eligible patients will be randomized in a 1:1 ratio to receive olaparib or platinum-based chemotherapy of the investigator’s choice.Major Eligibility CriteriaEligible patients must have high-grade serous or endometrioid ovarian cancer progressed during or after first-line poly (ADP-ribose) polymerase inhibitor maintenance therapy and must have undergone secondary cytoreductive surgery.Primary EndpointThe dual primary endpoints will include progression-free survival and progression-free survival 2. Progression-free survival is defined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as the time between randomization and progression or death from any cause. Progression-free survival 2 is defined by the investigator using RECIST version 1.1 as the time frame from randomization to the second progression or death from any cause after subsequent treatment.Sample SizeApproximately 200 patients will be enrolled in this study.Estimated Dates for Completing Accrual and Presenting ResultsEnrollment will be completed in 2024. Results will be presented in 2026.Trial RegistrationEudraCT 2021-000245-41NCT05255471
- Published
- 2022
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