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52. Centromere sliding on a mammalian chromosome

Author

Purgato, Stefania, Belloni, Elisa, Piras, Francesca M., Zoli, Monica, Badiale, Claudia, Cerutti, Federico, Mazzagatti, Alice, Perini, Giovanni, Della Valle, Giuliano, Nergadze, Solomon G., Sullivan, Kevin F., Raimondi, Elena, Rocchi, Mariano, and Giulotto, Elena

Published
2015
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54. Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Author

D'Agostino, Armando, Aguglia, Andrea, Barbui, Corrado, Bartoli, Francesco, Carrà, Giuseppe, Cavallotti, Simone, Chirico, Margherita, Ostinelli, Edoardo G, Zangani, Caroline, Martinotti, Giovanni, Ostuzzi, Giovanni, Bertolini, Federico, Calandra, Carmela, Callegari, Camilla, D’Agostino, Armando, Lucii, Claudio, Mastromo, Daniele, Moretti, Daniele, Monzani, Emiliano, Porcellana, Matteo, Prestia, Davide, Nose, Michela, Purgato, Marianna, Turrini, Giulia, Mazzi, Maria, Angela, Papola, Davide, Gastaldon, Chiara, Terlizzi, Samira, Piccoli, Alberto, Ruggeri, Mirella, De Fazio, Pasquale, Magliocco, Fabio, Caroleo, Mariarita, Raffaele, Gaetano, Ostinelli, Edoardo, Giuseppe, Bolognesi, Simone, Debolini, Sara, Pierantozzi, Elisa, Fargnoli, Francesco, Del Zanna, Maria, Giannini, Alessandra, Luccarelli, Livia, De Capua, Alberto, Annese, Pasqua, Maria, Cerretini, Massimiliano, Tozzi, Fiorella, Magnani, Nadia, Cardamone, Giuseppe, Bardicchia, Francesco, Facchi, Edvige, Soscia, Federica, Zotos, Spyridon, Biancosino, Bruno, Zonta, Filippo, Pompei, Francesco, Zizolfi, Daniele, Ielmini, Marta, Caselli, Ivano, Giana, Edoardo, Buzzi, Aldo, Emanuele, Diurni, Marcello, Milano, Anna, Sani, Emanuele, Calzolari, Roberta, Bortolaso, Paola, Piccinelli, Marco, Cazzamalli, Sara, Caterina, Alberini, Gabro, Piantanida, Silvia, Costantini, Chiara, Paronelli, Chiara, Di Caro, Angela, Moretti, Valentina, Gozzi, Mauro, D'Ippolito, Chiara, Barbanti Silva, Veronica, Papalini, Alessandro, Corbo, Mariangela, Campese, Ornella, Fiori, Federica, Lorusso, Marco, Di Capro, Lucia, Viceconte, Daniela, Mancini, Valerio, Suraniti, Francesco, Signorelli, Maria, Salvina, Rossi, Eugenio, Lupoli, Pasqualino, Menchetti, Marco, Terzi, Laura, Boso, Marianna, Risaro, Paolo, De Paoli, Giuseppe, Catania, Cristina, Tarricone, Ilaria, Caretto, Valentina, Storbini, Viviana, Emiliani, Roberta, Balzarro, Beatrice, Carra, Giuseppe, Tabacchi, Tommaso, Nava, Roberto, Bono, Adele, Provenzi, Milena, Brambilla, Giulia, Aspesi, Flora, Tremolada, Martina, Castagna, Gloria, Bava, Mattia, Verrengia, Enrica, Lucchi, Sara, Oriani, Maria, Ginevra, Barchiesi, Michela, Pacetti, Monica, Magni, Laura, Rosa, Rossi, Giuseppe, Beneduce, Rossella, Tura, Giovanni, Battista, Laffranchini, Laura, Ferrato, Farida, Restaino, Francesco, Limosani, Ivan, Ghio, Lucio, Ferro, Maurizio, Parise, Vincenzo, Fricchione, Balletta, Giovanni, Addeo, Lelio, De Vivo, Elisa, Di Benedetto, Rossella, Pinna, Federica, Carpiniello, Bernardo, Spano, Mariangela, Giacomin, Marzio, Pecile, Damiano, Mattei, Chiara, Fabrici, Elisabetta, Pascolo, Panarello, Sofia, Peresson, Giulia, Vitucci, Claudio, Bonavigo, Tommaso, Perini, Giovanni, Boschello, Filippo, Strizzolo, Stefania, Gardellin, Francesco, Di Giannantonio, Massimo, Fizzotti, Carlo, Cossetta, Edoardo, Di Gregorio, Luana, Sozzi, Francesca, Boncompagni, Giancarlo, La Barbera, Daniele, Colli, Giuseppe, Laurenzi, Sabrina, Luca, Maria, D'Agostino A., Aguglia A., Barbui C., Bartoli F., Carra G., Cavallotti S., Chirico M., Ostinelli E.G., Zangani C., Martinotti G., Ostuzzi G., Nose M., Purgato M., Turrini G., Mazzi M.A., Papola D., Gastaldon C., Terlizzi S., Bertolini F., Piccoli A., Ruggeri M., De Fazio P., Magliocco F., Caroleo M., Raffaele G., Bergamelli E., Lucii C., Bolognesi S., Debolini S., Pierantozzi E., Fargnoli F., Del Zanna M., Giannini A., Luccarelli L., De Capua A., Annese P.M., Cerretini M., Tozzi F., Magnani N., Cardamone G., Bardicchia F., Facchi E., Soscia F., Zotos S., Biancosino B., Zonta F., Pompei F., Callegari C., Zizolfi D., Poloni N., Ielmini M., Caselli I., Giana E., Buzzi A., Diurni M., Milano A., Sani E., Calzolari R., Bortolaso P., Piccinelli M., Cazzamalli S., Alberini G., Piantanida S., Costantini C., Paronelli C., Di Caro A., Moretti V., Gozzi M., D'Ippolito C., Barbanti S.V., Alessandro P., Corbo M., Campese O., Fiori F., Lorusso M., Di Capro L., Viceconte D., Mancini V., Suraniti F., Signorelli M.S., Rossi E., Lupoli P., Menchetti M., Terzi L., Boso M., Risaro P., De Paoli G., Catania C., Tarricone I., Caretto V., Storbini V., Emiliani R., Balzarro B., Tabacchi T., Nava R., Bono A., Provenzi M., Brambilla G., Aspesi F., Trotta G., Tremolada M., Castagna G., Bava M., Verrengia E., Lucchi S., Oriani M.G., Barchiesi M., Pacetti M., Amerio A., Amore M., Serafini G., Magni L.R., Rossi G., Beneduce R., Tura G.B., Laffranchini L., Mastromo D., Ferrato F., Restaino F., Monzani E., Porcellana M., Limosani I., Ghio L., Ferro M., Parise V.F., Balletta G., Addeo L., De Vivo E., Di Benedetto R., Pinna F., Carpiniello B., Spano M., Giacomin M., Pecile D., Mattei C., Fabrici E.P., Panarello S., Peresson G., Vitucci C., Bonavigo T., Perini G., Boschello F., Strizzolo S., Gardellin F., di Giannantonio M., Moretti D., Fizzotti C., Cossetta E., Di Gregorio L., Sozzi F., Boncompagni G., La Barbera D., Colli G., Laurenzi S., Calandra C., Luca M., D'Agostino, A, Aguglia, A, Barbui, C, Bartoli, F, Carra, G, Cavallotti, S, Chirico, M, Ostinelli, E, Zangani, C, Martinotti, G, Ostuzzi, G, D'Agostino, Armando, Aguglia, Andrea, Barbui, Corrado, Bartoli, Francesco, Carrà, Giuseppe, Cavallotti, Simone, Chirico, Margherita, Ostinelli, Edoardo G, Zangani, Caroline, Martinotti, Giovanni, Ostuzzi, Giovanni, and LA BARBERA, DANIELE

Subjects
Long-acting injectable antipsychotic, Cross-Sectional Studies, Off-label, Personality disorder, Bipolar disorder, Delayed-Action Preparations, Schizophrenia, Humans, Long-acting injectable antipsychotics, Off-Label Use, Antipsychotic Agents, Settore MED/25 - Psichiatria
Abstract

Introduction: Information on the off–label use of Long–Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on– vs off–label LAIs and predictors of off–label First– or Second–Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method: In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off– or on–label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off–label group. Results: SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on– and off–label use. Approximately 1 in 4 patients received an off–label prescription. In the off–label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p= 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p= 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion: Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off–label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co–morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns.

Published
2022

58. Direct and Coordinate Regulation of ATP-binding Cassette Transporter Genes by Myc Factors Generates Specific Transcription Signatures That Significantly Affect the Chemoresistance Phenotype of Cancer Cells

Author

Porro, Antonio, Haber, Michelle, Diolaiti, Daniel, Iraci, Nunzio, Henderson, Michelle, Gherardi, Samuele, Valli, Emanuele, Munoz, Marcia A., Xue, Chengyuan, Flemming, Claudia, Schwab, Manfred, Wong, Jason H., Marshall, Glenn M., Della Valle, Giuliano, Norris, Murray D., and Perini, Giovanni

Published
2010
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60. Fine Mapping of a Replication Origin of Human DNA

Author

Giacca, Mauro, Zentilin, Lorena, Norio, Paolo, Diviacco, Silvia, Dimitrova, Daniela, Contreas, Giovanna, Biamonti, Giuseppe, Perini, Giovanni, Weighardt, Florian, Riva, Silvano, and Falaschi, Arturo

Published
1994

62. PRDM12 in Health and Diseases

Author

Rienzo, Monica, primary, Di Zazzo, Erika, additional, Casamassimi, Amelia, additional, Gazzerro, Patrizia, additional, Perini, Giovanni, additional, Bifulco, Maurizio, additional, and Abbondanza, Ciro, additional

Published
2021
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63. Expression of spliced oncogenic Ikaros isoforms in Philadelphia-positive acute lymphoblastic leukemia patients treated with tyrosine kinase inhibitors: implications for a new mechanism of resistance

Author

Iacobucci, Ilaria, Lonetti, Annalisa, Messa, Francesca, Cilloni, Daniela, Arruga, Francesca, Ottaviani, Emanuela, Paolini, Stefania, Papayannidis, Cristina, Piccaluga, Pier Paolo, Giannoulia, Panagiota, Soverini, Simona, Amabile, Marilina, Poerio, Angela, Saglio, Giuseppe, Pane, Fabrizio, Berton, Giorgio, Baruzzi, Anna, Vitale, Antonella, Chiaretti, Sabina, Perini, Giovanni, Foà, Robin, Baccarani, Michele, and Martinelli, Giovanni

Published
2008
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65. CHAF1A Blocks Neuronal Differentiation and Promotes Neuroblastoma Oncogenesis via Metabolic Reprogramming

Author

Tao, Ling, primary, Moreno‐Smith, Myrthala, additional, Ibarra‐García‐Padilla, Rodrigo, additional, Milazzo, Giorgio, additional, Drolet, Nathan A., additional, Hernandez, Blanca E., additional, Oh, Young S., additional, Patel, Ivanshi, additional, Kim, Jean J., additional, Zorman, Barry, additional, Patel, Tajhal, additional, Kamal, Abu Hena Mostafa, additional, Zhao, Yanling, additional, Hicks, John, additional, Vasudevan, Sanjeev A., additional, Putluri, Nagireddy, additional, Coarfa, Cristian, additional, Sumazin, Pavel, additional, Perini, Giovanni, additional, Parchem, Ronald J., additional, Uribe, Rosa A., additional, and Barbieri, Eveline, additional

Published
2021
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66. Multi-omic analyses of the MYCN network unveil new potential vulnerabilities in childhood neuroblastoma

Author

Perini, Giovanni, Ciaccio, Roberto <1990>, Perini, Giovanni, and Ciaccio, Roberto <1990>

Abstract

Neuroblastoma is the first neurogenic-extracranial solid cancer occurring in infancy and childhood. The genetic aberration most commonly associated with a poor prognosis is MYCN gene’s amplification. We hypothesize that effective anti-MYC therapeutics can be developed by understanding the regulation and function of N-MYC in neuroblastoma. Since N-MYC is an intrinsically disordered protein, it is still challenging to target this transcription factor, however, the model is shifting significantly after discovering novel therapeutic targets that impact MYC-driven tumorigenesis. The following work explores how MYCN expression affects the induction and maintenance of neuroblastoma. By using different multi-omic approaches and many promising innovative techniques, we were able to identify and characterize new potential vulnerabilities of this pathology, which may work in concert with N-MYC for the instruction of a high-risk neuroblastoma phenotype. My studies’ first objective was to investigate whether and how N-MYC can regulate transcription of lncRNAs by comparing transcriptional profiles between non-amplified and MYCN-amplified neuroblastoma cells. Here, we singled out lncNB1, which is selectively higher expressed in high MYCN cells only and it is also firmly and almost uniquely transcribed in neuroblastoma among all types of cancers. Our data showed that N-MYC directly activates transcription of lncNB1, instructing a complex network of molecular interactions, ultimately resulting in increased N-MYC protein stability, reinforcing the N-MYC oncogenetic program. The second objective was to assess how high N-MYC expression may cooperate to establish a dynamic regulatory axis with the E2F3 transcription factor, impacting the development of the high-risk cancer phenotype. Taken together, our unbias screenings uncovered potential candidates that help to fill the knowledge gap in understanding what is the impact of N-MYC in childhood neuroblastoma, providing new opportunities

Published
2021

68. A G316A Polymorphism in the Ornithine Decarboxylase Gene Promoter Modulates MYCN-Driven Childhood Neuroblastoma

Author

Gamble, Laura D., primary, Purgato, Stefania, additional, Henderson, Michelle J., additional, Di Giacomo, Simone, additional, Russell, Amanda J., additional, Pigini, Paolo, additional, Murray, Jayne, additional, Valli, Emanuele, additional, Milazzo, Giorgio, additional, Giorgi, Federico M., additional, Cowley, Mark, additional, Ashton, Lesley J., additional, Bhalshankar, Jaydutt, additional, Schleiermacher, Gudrun, additional, Rihani, Ali, additional, Van Maerken, Tom, additional, Vandesompele, Jo, additional, Speleman, Frank, additional, Versteeg, Rogier, additional, Koster, Jan, additional, Eggert, Angelika, additional, Noguera, Rosa, additional, Stallings, Raymond L., additional, Tonini, Gian Paolo, additional, Fong, Kwun, additional, Vaksman, Zalman, additional, Diskin, Sharon J., additional, Maris, John M., additional, London, Wendy B., additional, Marshall, Glenn M., additional, Ziegler, David S., additional, Hogarty, Michael D., additional, Perini, Giovanni, additional, Norris, Murray D., additional, and Haber, Michelle, additional

Published
2021
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69. In vivo transcriptional regulation of N-Myc target genes is controlled by E-box methylation

Author

Perini, Giovanni, Diolaiti, Daniel, Porro, Antonio, and Valle, Giuliano Della

Subjects
Chromatin -- Research, Neuroblastoma -- Research, Science and technology
Abstract

N-Myc is a transcription factor that forms heterodimers with the protein Max and binds gene promoters by recognizing a DNA sequence, CACGTG, called E-box. The identification of N-myc target genes is an important step for understanding N-Myc biological functions in both physiological and pathological contexts. In this study, we describe the identification of N-Myc-responsive genes through chromatin immunoprecipitation and methylation-sensitive restriction analysis. Results show that N-Myc is a direct regulator of several identified genes, and that methylation of the CpG dinucleotide within the E-box prevents the access of N-Myc to gene promoters in vivo. Furthermore, methylation profile of the E-box within the promoters of EGFR and CASP8, two genes directly controlled by Myc, is cell type-specific, suggesting that differential E-box methylation may contribute to generating unique patterns of Myc-dependent transcription. This study illuminates a central role of DNA methylation in controlling N-Myc occupancy at gene promoters and modulating its transcriptional activity in cancer cells. chromatin immunoprecipitation | neuroblastoma | C-Myc | EGFR | Caspase 8

Published
2005

71. ABCC Multidrug Transporters in Childhood Neuroblastoma: Clinical and Biological Effects Independent of Cytotoxic Drug Efflux

Author

Henderson, Michelle J., Haber, Michelle, Porro, Antonio, Munoz, Marcia A., Iraci, Nunzio, Xue, Chengyuan, Murray, Jayne, Flemming, Claudia L., Smith, Janice, Fletcher, Jamie I., Gherardi, Samuele, Kwek, Chin-Kiat, Russell, Amanda J., Valli, Emanuele, London, Wendy B., Buxton, Allen B., Ashton, Lesley J., Sartorelli, Alan C., Cohn, Susan L., Schwab, Manfred, Marshall, Glenn M., Perini, Giovanni, and Norris, Murray D.

Published
2011
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74. Withdrawal: Nitric oxide protects neuroblastoma cells from apoptosis induced by serum deprivation through cAMP-response element-binding protein (CREB) activation

Author

Ciani, Elisabetta, Guidi, Sandra, Della Valle, Giuliano, Perini, Giovanni, Bartesaghi, Renata, and Contestabile, Antonio

Subjects
Time Factors, Transcription, Genetic, Cell Survival, Blotting, Western, Tetrazolium Salts, Apoptosis, Enzyme-Linked Immunosorbent Assay, Nitric Oxide, Transfection, Biochemistry, Culture Media, Serum-Free, Neuroblastoma, Genes, Reporter, In Situ Nick-End Labeling, Tumor Cells, Cultured, Humans, Protein Isoforms, Withdrawals/Retractions, Phosphorylation, Cyclic AMP Response Element-Binding Protein, Luciferases, Molecular Biology, Nitrites, Neurons, Dose-Response Relationship, Drug, Colforsin, Cell Biology, Cyclic AMP-Dependent Protein Kinases, Thiazoles, Microscopy, Fluorescence, Mutation, Plasmids
Abstract

The transcription factor cAMP-response element-binding protein (CREB) mediates survival in many cells, including neurons. Recently, death of cerebellar granule neurons due to nitric oxide (NO) deprivation was shown to be accompanied by down-regulation of CREB activity (). We now provide evidence that overproduction of endogenous NO or supplementation with exogenous NO renders SK-N-BE human neuroblastoma cells more resistant to apoptosis induced by serum deprivation. Parental cells underwent apoptosis after 24 h of serum deprivation, an outcome largely absent in clones overexpressing human neuronal nitric oxide synthase (nNOS). This protective effect was reversed by the inhibition of NOS itself or soluble guanylyl cyclase, pointing at cGMP as an intermediate effector of NO-mediated rescue. A slow-releasing NO donor protected parental cells to a significant extent, thus confirming the survival effect of NO. The impaired viability of serum-deprived parental cells was accompanied by a strong decrease of CREB phosphorylation and transcriptional activity, effects significantly attenuated in nNOS-overexpressing clones. To confirm the role of CREB in survival, the ectopic expression of CREB and/or protein kinase A largely counteracted serum deprivation-induced cell death of SK-N-BE cells, whereas transfection with a CREB negative mutant was ineffective. These experiments indicate that CREB activity is an important step for NO-mediated survival in neuronal cells.

Published
2020

75. Reasons for initiating long-acting antipsychotics in psychiatric practice: findings from the STAR Network Depot Study

Author

Barbui, Corrado, Bertolini, Federico, Bartoli, Francesco, Calandra, Carmela, Callegari, Camilla, Carrà, Giuseppe, D’Agostino, Armando, Lucii, Claudio, Martinotti, Giovanni, Mastromo, Daniele, Moretti, Daniele, Monzani, Emiliano, Porcellana, Matteo, Prestia, Davide, Ostuzzi, Giovanni, Nose, Michela, Purgato, Marianna, Turrini, Giulia, Mazzi, Maria, Angela, Papola, Davide, Gastaldon, Chiara, Terlizzi, Samira, Piccoli, Alberto, Ruggeri, Mirella, De Fazio, Pasquale, Magliocco, Fabio, Caroleo, Mariarita, Raffaele, Gaetano, D'Agostino, Armando, Ostinelli, Edoardo, Giuseppe, Chirico, Margherita, Cavallotti, Simone, Bolognesi, Simone, Debolini, Sara, Pierantozzi, Elisa, Fargnoli, Francesco, Del Zanna, Maria, Giannini, Alessandra, Luccarelli, Livia, De Capua, Alberto, Annese, Pasqua, Maria, Cerretini, Massimiliano, Tozzi, Fiorella, Magnani, Nadia, Cardamone, Giuseppe, Bardicchia, Francesco, Facchi, Edvige, Soscia, Federica, Zotos, Spyridon, Biancosino, Bruno, Zonta, Filippo, Pompei, Francesco, Zizolfi, Daniele, Poloni, Nicola, Ielmini, Marta, Caselli, Ivano, Giana, Edoardo, Buzzi, Aldo, Emanuele, Diurni, Marcello, Milano, Anna, Sani, Emanuele, Calzolari, Roberta, Bortolaso, Paola, Piccinelli, Marco, Cazzamalli, Sara, Caterina, Alberini, Gabro, Piantanida, Silvia, Costantini, Chiara, Paronelli, Chiara, Di Caro, Angela, Moretti, Valentina, Gozzi, Mauro, D'Ippolito, Chiara, Barbanti Silva, Veronica, Papalini, Alessandro, Corbo, Mariangela, Campese, Ornella, Fiori, Federica, Lorusso, Marco, Di Capro, Lucia, Viceconte, Daniela, Mancini, Valerio, Suraniti, Francesco, Signorelli, Maria, Salvina, Rossi, Eugenio, Lupoli, Pasqualino, Menchetti, Marco, Terzi, Laura, Boso, Marianna, Risaro, Paolo, De Paoli, Giuseppe, Catania, Cristina, Tarricone, Ilaria, Caretto, Valentina, Storbini, Viviana, Emiliani, Roberta, Balzarro, Beatrice, Carra, Giuseppe, Tabacchi, Tommaso, Nava, Roberto, Bono, Adele, Provenzi, Milena, Brambilla, Giulia, Aspesi, Flora, Tremolada, Martina, Castagna, Gloria, Bava, Mattia, Verrengia, Enrica, Lucchi, Sara, Oriani, Maria, Ginevra, Barchiesi, Michela, Pacetti, Monica, Aguglia, Andrea, Magni, Laura, Rosa, Rossi, Giuseppe, Beneduce, Rossella, Tura, Giovanni, Battista, Laffranchini, Laura, Ferrato, Farida, Restaino, Francesco, Limosani, Ivan, Ghio, Lucio, Ferro, Maurizio, Parise, Vincenzo, Fricchione, Balletta, Giovanni, Addeo, Lelio, De Vivo, Elisa, Di Benedetto, Rossella, Pinna, Federica, Carpiniello, Bernardo, Spano, Mariangela, Giacomin, Marzio, Pecile, Damiano, Mattei, Chiara, Fabrici, Elisabetta, Pascolo, Panarello, Sofia, Peresson, Giulia, Vitucci, Claudio, Bonavigo, Tommaso, Perini, Giovanni, Boschello, Filippo, Strizzolo, Stefania, Gardellin, Francesco, Di Giannantonio, Massimo, Fizzotti, Carlo, Cossetta, Edoardo, Di Gregorio, Luana, Sozzi, Francesca, Boncompagni, Giancarlo, La Barbera, Daniele, Colli, Giuseppe, Laurenzi, Sabrina, Luca, Maria, Crocamo, Carlo, Barbui, C, Bertolini, F, Bartoli, F, Calandra, C, Callegari, C, Carrà, G, D'Agostino, A, Lucii, C, Martinotti, G, Mastromo, D, Moretti, D, Monzani, E, Porcellana, M, Prestia, D, and Ostuzzi, G

Subjects
medicine.medical_specialty, psychiatric practice, lcsh:RC435-571, Treatment adherence, viruses, medicine.medical_treatment, antipsychotic, long-acting injectable, prescribing attitudes, survey, immune system diseases, lcsh:Psychiatry, medicine, Psychiatry, Antipsychotic, prescribing attitude, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Original Research, business.industry, lcsh:RM1-950, virus diseases, lcsh:Therapeutics. Pharmacology, Long acting, Psychology (miscellaneous), business
Abstract

Background: Long acting injectable (LAI) antipsychotics have been claimed to ensure treatment adherence and possibly reduce the daily burden of oral formulations. So far, only surveys investigating the theoretical prescribing attitudes of clinicians have been employed. On this basis, we aimed to investigate reasons for prescribing LAIs in a real-world, unselected sample of patients. Methods: The STAR Network Depot Study is an observational, multicentre study consecutively enrolling adults initiating a LAI over a 12-months period. Clinical severity was assessed with the Brief Psychiatric Rating Scale, and patient’s attitude toward medications with the Drug Attitude Inventory 10 items. Psychiatrists recorded reasons for LAI prescribing for each study participant. Responses were grouped into six non-mutually exclusive categories: aggressiveness, patient engagement, ease of drug taking, side-effects, stigma, adherence. Results: Of the 451 patients included, two-thirds suffered from chronic psychoses. Improving patient engagement with the outpatient psychiatric service was the most common reason for prescribing LAIs (almost 80% of participants), followed by increasing treatment adherence (57%), decreasing aggressiveness (54%), and improving ease of drug taking (52%). After adjusting for confounders, logistic regression analyses showed that reasons for LAI use were associated with LAI choice (e.g. first-generation LAIs for reducing aggressiveness). Conclusion: Despite the wide availability of novel LAI formulation and the emphasis on their wider use, our data suggest that the main reasons for LAI use have remained substantially unchanged over the years, focusing mostly on improving patient’s engagement. Further, clinicians follow implicit prescribing patterns when choosing LAIs, and this may generate hypotheses for future experimental studies.

Published
2020

78. Recognition of bZIP proteins by the human T-cell leukaemia virus transactivator Tax

Author

Perini, Giovanni, Wagner, Susanne, and Green, Michael R.

Subjects
HTLV (Viruses) -- Physiological aspects, DNA binding proteins -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The human T-cell leukemia virus transactivator Tax interacts with the basic region of bZIP proteins, enhancing their DNA binding ability while stimulating bZIP dimerization. Though no specific leucine zipper is required, Tax alters the DNA site selection by creating an affinity to specific DNA binding sites for the Tax-bZIP complexes. This behavior suggests that transcription factor dimerization control is a common regulatory mode.

Published
1995

80. Expression of doxorubicin-daunorubicin resistance genes in different anthracycline-producing mutants of Streptomyces peucetius

Author

Colombo, Anna L., Solinas, Maria M., Perini, Giovanni, Biamonti, Giuseppe, Zanella, Giuseppe, Caruso, Marinella, Torti, Francesca, Filippini, Silvia, Inventi-Solari, Augusto, and Garofano, Luisa

Subjects
Drug resistance in microorganisms -- Genetic aspects, Streptomyces -- Genetic aspects, Anthracyclines -- Physiological aspects, Biological sciences
Abstract

The expression of doxorubicin gene (ric1) and daunorubicin (ric2) in the different mutant strains of Streptomyces peucetius was investigated using Northern blot analysis of RNA transcripts from these genes. Results reveal that the concentration of RNA transcript is higher in strain 7600 than in strain 7900. Two other mutants, strain 8600 and strain 9700 did not express the transcript although both strains were derived from strain 7900. ric1 and ric2 exhibit different restriction patterns and are not homologous, however, both genes confer resistance to the strains producing them.

Published
1992

81. Erratum to: Centromere sliding on a mammalian chromosome

Author

Purgato, Stefania, Belloni, Elisa, Piras, Francesca M., Zoli, Monica, Badiale, Claudia, Cerutti, Federico, Mazzagatti, Alice, Perini, Giovanni, Della Valle, Giuliano, Nergadze, Solomon G., Sullivan, Kevin F., Raimondi, Elena, Rocchi, Mariano, and Giulotto, Elena

Published
2015
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84. The absence of dystrophin brain isoform expression in healthy human heart ventricles explains the pathogenesis of 5' X-linked dilated cardiomyopathy

Author

Neri Marcella, Valli Emanuele, Alfano Giovanna, Bovolenta Matteo, Spitali Pietro, Rapezzi Claudio, Muntoni Francesco, Banfi Sandro, Perini Giovanni, Gualandi Francesca, and Ferlini Alessandra

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background In X-linked dilated cardiomyopathy due to dystrophin mutations which abolish the expression of the M isoform (5'-XLDC), the skeletal muscle is spared through the up-regulation of the Brain (B) isoform, a compensatory mechanism that does not appear to occur in the heart of affected individuals. Methods We quantitatively studied the expression topography of both B and M isoforms in various human heart regions through in-situ RNA hybridization, Reverse-Transcriptase and Real-Time PCR experiments. We also investigated the methylation profile of the B promoter region in the heart and quantified the B isoform up regulation in the skeletal muscle of two 5'-XLDC patients. Results Unlike the M isoform, consistently detectable in all the heart regions, the B isoform was selectively expressed in atrial cardiomyocytes, but absent in ventricles and in conduction system structures. Although the level of B isoform messenger in the skeletal muscle of 5'-XLDC patients was lower that of the M messenger present in control muscle, it seems sufficient to avoid an overt muscle pathology. This result is consistent with the protein level in XLDC patients muscles we previously quantified. Methylation studies revealed that the B promoter shows an overall low level of methylation at the CG dinucleotides in both atria and ventricles, suggesting a methylation-independent regulation of the B promoter activity. Conclusions The ventricular dilatation seen in 5'-XLDC patients appears to be functionally related to loss of the M isoform, the only isoform transcribed in human ventricles; in contrast, the B isoform is well expressed in heart but confined to the atria. Since the B isoform can functionally replace the M isoform in the skeletal muscle, its expression in the heart could potentially exert the same rescue function. Methylation status does not seem to play a role in the differential B promoter activity in atria and ventricles, which may be governed by other regulatory mechanisms. If these mechanisms could be deduced, de-silencing of the B isoform may represent a therapeutic strategy in 5'-XLDC patients.

Published
2012
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85. The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35

Author

Liu, Pei Y., primary, Tee, Andrew E., additional, Milazzo, Giorgio, additional, Hannan, Katherine M., additional, Maag, Jesper, additional, Mondal, Sujanna, additional, Atmadibrata, Bernard, additional, Bartonicek, Nenad, additional, Peng, Hui, additional, Ho, Nicholas, additional, Mayoh, Chelsea, additional, Ciaccio, Roberto, additional, Sun, Yuting, additional, Henderson, Michelle J., additional, Gao, Jixuan, additional, Everaert, Celine, additional, Hulme, Amy J., additional, Wong, Matthew, additional, Lan, Qing, additional, Cheung, Belamy B., additional, Shi, Leming, additional, Wang, Jenny Y., additional, Simon, Thorsten, additional, Fischer, Matthias, additional, Zhang, Xu D., additional, Marshall, Glenn M., additional, Norris, Murray D., additional, Haber, Michelle, additional, Vandesompele, Jo, additional, Li, Jinyan, additional, Mestdagh, Pieter, additional, Hannan, Ross D., additional, Dinger, Marcel E., additional, Perini, Giovanni, additional, and Liu, Tao, additional

Published
2019
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86. Drugging MYCN Oncogenic Signaling through the MYCN-PA2G4 Binding Interface

Author

Koach, Jessica, primary, Holien, Jessica K., additional, Massudi, Hassina, additional, Carter, Daniel R., additional, Ciampa, Olivia C., additional, Herath, Mika, additional, Lim, Taylor, additional, Seneviratne, Janith A., additional, Milazzo, Giorgio, additional, Murray, Jayne E., additional, McCarroll, Joshua A., additional, Liu, Bing, additional, Mayoh, Chelsea, additional, Keenan, Bryce, additional, Stevenson, Brendan W., additional, Gorman, Michael A., additional, Bell, Jessica L., additional, Doughty, Larissa, additional, Hüttelmaier, Stefan, additional, Oberthuer, Andre, additional, Fischer, Matthias, additional, Gifford, Andrew J., additional, Liu, Tao, additional, Zhang, Xiaoling, additional, Zhu, Shizhen, additional, Gustafson, W. Clay, additional, Haber, Michelle, additional, Norris, Murray D., additional, Fletcher, Jamie I., additional, Perini, Giovanni, additional, Parker, Michael W., additional, Cheung, Belamy B., additional, and Marshall, Glenn M., additional

Published
2019
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87. Abstract 2616: A novel iron-chelating agent reduces MYC transcription via E2F gene family regulation

Author

Valli, Emanuele, primary, Xue, Chengyuan, additional, Cheung, Leanna, additional, Gamble, Laura, additional, Pandher, Ruby, additional, Giacomo, Simone Di, additional, Burkhart, Catherine, additional, Fedtsova, Natalia, additional, Ferrucci, Francesca, additional, Makarov, Sergei, additional, Telfer, Thomas, additional, Codd, Rachel, additional, Scott, David, additional, Perini, Giovanni, additional, Osterman, Andrei, additional, Gudkov, Andrei, additional, Norris, Murray, additional, and Haber, Michelle, additional

Published
2019
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89. Neuroblastoma targeted therapy: employment of CRISPR gene-editing to explore relevant markers and potential targets in aggressive tumours

Author

Perini, Giovanni, Pigini, Paolo <1991>, Perini, Giovanni, and Pigini, Paolo <1991>

Abstract

Neuroblastoma is a tumour originating from the sympathetic nervous system, and represents the most common extracranial solid cancer in childhood. Despite the malignancy is extremely heterogeneous, about 25% of all cases is characterized by MYCN-gene amplification, aggressive tumour and poor survival. The network of genes that are deregulated in this group of patients represents a focal point for targeted-therapy discovery. Along this research line, the first objective of the present project was to investigate the prognostic significance of a single nucleotide polymorphism (SNP) located in the promoter of ODC1, a neuroblastoma prognostic marker involved in polyamine biosynthesis. The SNP genotype was first associated with survival of a large cohort of patients with aggressive neuroblastoma. Then, CRISPR-editing revealed that the SNP genotype affects ODC1 expression and proliferation of neuroblastoma cells. At last, the SNP was found to influence cell sensibility to DFMO, an ODC1 inhibitor that is currently under trial for treatment of aggressive neuroblastoma. The second objective was to investigate the role in neuroblastoma development and progression of RUNX1T1, a poorly studied transcription repressor involved in distinct development events and cancers. Survival analysis of a cohort of neuroblastoma patients revealed that RUNX1T1 is a potential oncosuppressor. In apparent contrast, RUNX1T1 knockout by CRISPR-editing demonstrated that the gene promotes aggressiveness of neuroblastoma cells. Transcriptome analysis of the mutant cells then evidenced deregulation of a significant number of genes and pathways that are prognostic markers in neuroblastoma, therefore depicting a multifunctional regulation network that could be exploited for new therapies. The third and last objective was to test a novel therapeutic approach based on MYCN-amplification targeting via CRISPR-cleavage. In vitro experiments demonstrated that the system efficiently and specifically impairs the

Published
2019

90. Inhibition of polyamine synthesis and uptake reduces tumor progression and prolongs survival in mouse models of neuroblastoma

Author

Gamble, Laura D., Purgato, Stefania, Murray, Jayne, Xiao, Lin, Yu, Denise M. T., Hanssen, Kimberley M., Giorgi, Federico M., Carter, Daniel R., Gifford, Andrew J., Valli, Emanuele, Milazzo, Giorgio, Kamili, Alvin, Mayoh, Chelsea, Liu, Bing, Eden, Georgina, Sarraf, Sara, Allan, Sophie, Di Giacomo, Simone, Flemming, Claudia L., Russell, Amanda J., Cheung, Belamy B., Oberthuer, Andre, London, Wendy B., Fischer, Matthias, Trahair, Toby N., Fletcher, Jamie, I, Marshall, Glenn M., Ziegler, David S., Hogarty, Michael D., Burns, Mark R., Perini, Giovanni, Norris, Murray D., Haber, Michelle, Gamble, Laura D., Purgato, Stefania, Murray, Jayne, Xiao, Lin, Yu, Denise M. T., Hanssen, Kimberley M., Giorgi, Federico M., Carter, Daniel R., Gifford, Andrew J., Valli, Emanuele, Milazzo, Giorgio, Kamili, Alvin, Mayoh, Chelsea, Liu, Bing, Eden, Georgina, Sarraf, Sara, Allan, Sophie, Di Giacomo, Simone, Flemming, Claudia L., Russell, Amanda J., Cheung, Belamy B., Oberthuer, Andre, London, Wendy B., Fischer, Matthias, Trahair, Toby N., Fletcher, Jamie, I, Marshall, Glenn M., Ziegler, David S., Hogarty, Michael D., Burns, Mark R., Perini, Giovanni, Norris, Murray D., and Haber, Michelle

Abstract

Amplification of the MYCN oncogene is associated with an aggressive phenotype and poor outcome in childhood neuroblastoma. Polyamines are highly regulated essential cations that are frequently elevated in cancer cells, and the rate-limiting enzyme in polyamine synthesis, ornithine decarboxylase 1 (ODC1), is a direct transcriptional target of MYCN. Treatment of neuroblastoma cells with the ODC1 inhibitor difluoromethylornithine (DFMO), although a promising therapeutic strategy, is only partially effective at impeding neuroblastoma cell growth due to activation of compensatory mechanisms resulting in increased polyamine uptake from the surrounding microenvironment. In this study, we identified solute carrier family 3 member 2 (SLC3A2) as the key transporter involved in polyamine uptake in neuroblastoma. Knockdown of SLC3A2 in neuroblastoma cells reduced the uptake of the radiolabeled polyamine spermidine, and DFMO treatment increased SLC3A2 protein. In addition, MYCN directly increased polyamine synthesis and promoted neuroblastoma cell proliferation by regulating SLC3A2 and other regulatory components of the polyamine pathway. Inhibiting polyamine uptake with the small-molecule drug AMXT 1501, in combination with DFMO, prevented or delayed tumor development in neuroblastoma-prone mice and extended survival in rodent models of established tumors. Our findings suggest that combining AMXT 1501 and DFMO with standard chemotherapy might be an effective strategy for treating neuroblastoma.

Published
2019

91. Drugging MYCN Oncogenic Signaling through the MYCN-PA2G4 Binding Interface

Author

Koach, Jessica, Holien, Jessica K., Massudi, Hassina, Carter, Daniel R., Ciampa, Olivia C., Herath, Mika, Lim, Taylor, Seneviratne, Janith A., Milazzo, Giorgio, Murray, Jayne E., McCarroll, Joshua A., Liu, Bing, Mayoh, Chelsea, Keenan, Bryce, Stevenson, Brendan W., Gorman, Michael A., Bell, Jessica L., Doughty, Larissa, Huettelmaier, Stefan, Oberthuer, Andre, Fischer, Matthias, Gifford, Andrew J., Liu, Tao, Zhang, Xiaoling, Zhu, Shizhen, Gustafson, W. Clay, Haber, Michelle, Norris, Murray D., Fletcher, Jamie I., Perini, Giovanni, Parker, Michael W., Cheung, Belamy B., Marshall, Glenn M., Koach, Jessica, Holien, Jessica K., Massudi, Hassina, Carter, Daniel R., Ciampa, Olivia C., Herath, Mika, Lim, Taylor, Seneviratne, Janith A., Milazzo, Giorgio, Murray, Jayne E., McCarroll, Joshua A., Liu, Bing, Mayoh, Chelsea, Keenan, Bryce, Stevenson, Brendan W., Gorman, Michael A., Bell, Jessica L., Doughty, Larissa, Huettelmaier, Stefan, Oberthuer, Andre, Fischer, Matthias, Gifford, Andrew J., Liu, Tao, Zhang, Xiaoling, Zhu, Shizhen, Gustafson, W. Clay, Haber, Michelle, Norris, Murray D., Fletcher, Jamie I., Perini, Giovanni, Parker, Michael W., Cheung, Belamy B., and Marshall, Glenn M.

Abstract

MYCN is a major driver for the childhood cancer, neuroblastoma, however, there are no inhibitors of this target. Enhanced MYCN protein stability is a key component of MYCN oncogenesis and is maintained by multiple feedforward expression loops involving MYCN transactivation target genes. Here, we reveal the oncogenic role of a novel MYCN target and binding protein, proliferation-associated 2AG4 (PA2G4). Chromatin immunoprecipitation studies demonstrated that MYCN occupies the PA2G4 gene promoter, stimulating transcription. Direct binding of PA2G4 to MYCN protein blocked proteolysis of MYCN and enhanced colony formation in a MYCN-dependent manner. Using molecular modeling, surface plasmon resonance, and mutagenesis studies, we mapped the MYCN-PA2G4 interaction site to a 14 amino acid MYCN sequence and a surface crevice of PA2G4. Competitive chemical inhibition of the MYCN-PA2G4 protein-protein interface had potent inhibitory effects on neuroblastoma tumorigenesis in vivo. Treated tumors showed reduced levels of both MYCN and PA2G4. Our findings demonstrate a critical role for PA2G4 as a cofactor in MYCN-driven neuroblastoma and highlight competitive inhibition of the PA2G4-MYCN protein binding as a novel therapeutic strategy in the disease. Significance: Competitive chemical inhibition of the PA2G4-MYCN protein interface provides a basis for drug design of small molecules targeting MYC and MYCN-binding partners in malignancies driven by MYC family oncoproteins.

Published
2019

92. The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35

Author

Liu, Pei Y., Tee, Andrew E., Milazzo, Giorgio, Hannan, Katherine M., Maag, Jesper, Mondal, Sujanna, Atmadibrata, Bernard, Bartonicek, Nenad, Peng, Hui, Ho, Nicholas, Mayoh, Chelsea, Ciaccio, Roberto, Sun, Yuting, Henderson, Michelle J., Gao, Jixuan, Everaert, Celine, Hulme, Amy J., Wong, Matthew, Lan, Qing, Cheung, Belamy B., Shi, Leming, Wang, Jenny Y., Simon, Thorsten, Fischer, Matthias, Zhang, Xu D., Marshall, Glenn M., Norris, Murray D., Haber, Michelle, Vandesompele, Jo, Li, Jinyan, Mestdagh, Pieter, Hannan, Ross D., Dinger, Marcel E., Perini, Giovanni, Liu, Tao, Liu, Pei Y., Tee, Andrew E., Milazzo, Giorgio, Hannan, Katherine M., Maag, Jesper, Mondal, Sujanna, Atmadibrata, Bernard, Bartonicek, Nenad, Peng, Hui, Ho, Nicholas, Mayoh, Chelsea, Ciaccio, Roberto, Sun, Yuting, Henderson, Michelle J., Gao, Jixuan, Everaert, Celine, Hulme, Amy J., Wong, Matthew, Lan, Qing, Cheung, Belamy B., Shi, Leming, Wang, Jenny Y., Simon, Thorsten, Fischer, Matthias, Zhang, Xu D., Marshall, Glenn M., Norris, Murray D., Haber, Michelle, Vandesompele, Jo, Li, Jinyan, Mestdagh, Pieter, Hannan, Ross D., Dinger, Marcel E., Perini, Giovanni, and Liu, Tao

Abstract

The majority of patients with neuroblastoma due to MYCN oncogene amplification and consequent N-Myc oncoprotein over-expression die of the disease. Here our analyses of RNA sequencing data identify the long noncoding RNA lncNB1 as one of the transcripts most overexpressed in MYCN-amplified, compared with MYCN-non-amplified, human neuroblastoma cells and also the most over-expressed in neuroblastoma compared with all other cancers. lncNB1 binds to the ribosomal protein RPL35 to enhance E2F1 protein synthesis, leading to DEPDC1B gene transcription. The GTPase-activating protein DEPDC1B induces ERK protein phosphorylation and N-Myc protein stabilization. Importantly, lncNB1 knockdown abolishes neuroblastoma cell clonogenic capacity in vitro and leads to neuroblastoma tumor regression in mice, while high levels of lncNB1 and RPL35 in human neuroblastoma tissues predict poor patient prognosis. This study therefore identifies lncNB1 and its binding protein RPL35 as key factors for promoting E2F1 protein synthesis, N-Myc protein stability and N-Myc-driven oncogenesis, and as therapeutic targets.

Published
2019

94. Inhibition of polyamine synthesis and uptake reduces tumor progression and prolongs survival in mouse models of neuroblastoma

Author

Gamble, Laura D., primary, Purgato, Stefania, additional, Murray, Jayne, additional, Xiao, Lin, additional, Yu, Denise M. T., additional, Hanssen, Kimberley M., additional, Giorgi, Federico M., additional, Carter, Daniel R., additional, Gifford, Andrew J., additional, Valli, Emanuele, additional, Milazzo, Giorgio, additional, Kamili, Alvin, additional, Mayoh, Chelsea, additional, Liu, Bing, additional, Eden, Georgina, additional, Sarraf, Sara, additional, Allan, Sophie, additional, Di Giacomo, Simone, additional, Flemming, Claudia L., additional, Russell, Amanda J., additional, Cheung, Belamy B., additional, Oberthuer, Andre, additional, London, Wendy B., additional, Fischer, Matthias, additional, Trahair, Toby N., additional, Fletcher, Jamie I., additional, Marshall, Glenn M., additional, Ziegler, David S., additional, Hogarty, Michael D., additional, Burns, Mark R., additional, Perini, Giovanni, additional, Norris, Murray D., additional, and Haber, Michelle, additional

Published
2019
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95. A new BCR-ABL1 Drosophila model as a powerful tool to elucidate the pathogenesis and progression of chronic myeloid leukemia

Author

Bernardoni, Roberto, primary, Giordani, Giorgia, additional, Signorino, Elisabetta, additional, Monticelli, Sara, additional, Messa, Francesca, additional, Pradotto, Monica, additional, Rosso, Valentina, additional, Bracco, Enrico, additional, Giangrande, Angela, additional, Perini, Giovanni, additional, Saglio, Giuseppe, additional, and Cilloni, Daniela, additional

Published
2018
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97. Abstract 2453: Eradication of neuroblastoma by suppressing the expression of a single noncoding RNA

Author

Tee, Andrew E., primary, Liu, Pei Y., additional, Milazzo, Giorgio, additional, Hannan, Kate M., additional, Maag, Jesper, additional, Bartonicek, Nenad, additional, Song, Renhua, additional, Jiang, Chen C., additional, Zhang, Xu D., additional, Norris, Murray D., additional, Haber, Michelle, additional, Marshall, Glenn M., additional, Li, Jinyan, additional, Vandesompele, Jo, additional, Mattick, John S., additional, Mestdagh, Pieter, additional, Perini, Giovanni, additional, Hannan, Ross D., additional, Dinger, Marcel E., additional, and Liu, Tao, additional

Published
2018
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99. Factors associated with first- versus second-generation long-acting antipsychotics prescribed under ordinary clinical practice in Italy

Author

Ostuzzi, G, Mazzi, M, Terlizzi, S, Bertolini, F, Aguglia, A, Bartoli, F, Bortolaso, P, Callegari, C, Caroleo, M, Carrà, G, Corbo, M, D'Agostino, A, Gastaldon, C, Lucii, C, Magliocco, F, Martinotti, G, Nosé, M, Ostinelli, E, Papola, D, Piccinelli, M, Piccoli, A, Purgato, M, Tabacchi, T, Turrini, G, Ruggeri, M, Barbui, C, De Fazio, P, Raffaele, G, Chirico, M, Cavallotti, S, Bolognesi, S, Debolini, S, Pierantozzi, E, Fargnoli, F, Del Zanna, M, Giannini, A, Luccarelli, L, De Capua, A, Annese, P, Cerretini, M, Tozzi, F, Magnani, N, Cardamone, G, Bardicchia, F, Facchi, E, Soscia, F, Zotos, S, Biancosino, B, Zonta, F, Pompei, F, Zizolfi, D, Poloni, N, Ielmini, M, Caselli, I, Giana, E, Buzzi, A, Diurni, M, Milano, A, Sani, E, Calzolari, R, Cazzamalli, S, Alberini, G, Piantanida, S, Costantini, C, Paronelli, C, Di Caro, A, Moretti, V, Gozzi, M, D'Ippolito, C, Barbanti, S, Alessandro, P, Campese, O, Fiori, F, Lorusso, M, Di Capro, L, Viceconte, D, Mancini, V, Suraniti, F, Signorelli, M, Rossi, E, Lupoli, P, Menchetti, M, Terzi, L, Boso, M, Risaro, P, De Paoli, G, Catania, C, Tarricone, I, Caretto, V, Storbini, V, Emiliani, R, Balzarro, B, Nava, R, Bono, A, Provenzi, M, Brambilla, G, Aspesi, F, Tremolada, M, Castagna, G, Bava, M, Verrengia, E, Lucchi, S, Oriani, M, Barchiesi, M, Pacetti, M, Magni, L, Rossi, G, Beneduce, R, Tura, G, Laffranchini, L, Mastromo, D, Ferrato, F, Restaino, F, Monzani, E, Porcellana, M, Limosani, I, Ghio, L, Ferro, M, Parise, V, Balletta, G, Addeo, L, De Vivo, E, Benedetto, R, Pinna, F, Carpiniello, B, Spano, M, Giacomin, M, Pecile, D, Mattei, C, Fabrici, E, Panarello, S, Peresson, G, Vitucci, C, Bonavigo, T, Perini, G, Boschello, F, Strizzolo, S, Gardellin, F, Di Giannantonio, M, Moretti, D, Fizzotti, C, Cossetta, E, Gregorio, L, Sozzi, F, Boncompagni, G, Barbera, D, Colli, G, Laurenzi, S, Calandra, C, Luca, M, Ostuzzi, Giovanni, Mazzi, Maria Angela, Terlizzi, Samira, Bertolini, Federico, Aguglia, Andrea, Bartoli, Francesco, Bortolaso, Paola, Callegari, Camilla, Caroleo, Mariarita, Carrà, Giuseppe, Corbo, Mariangela, D'Agostino, Armando, Gastaldon, Chiara, Lucii, Claudio, Magliocco, Fabio, Martinotti, Giovanni, Nosé, Michela, Ostinelli, Edoardo Giuseppe, Papola, Davide, Piccinelli, Marco Piero, Piccoli, Alberto, Purgato, Marianna, Tabacchi, Tommaso, Turrini, Giulia, Ruggeri, Mirella, Barbui, Corrado, De Fazio, Pasquale, Raffaele, Gaetano, Chirico, Margherita, Cavallotti, Simone, Bolognesi, Simone, Debolini, Sara, Pierantozzi, Elisa, Fargnoli, Francesco, Del Zanna, Maria, Giannini, Alessandra, Luccarelli, Livia, De Capua, Alberto, Annese, Pasqua Maria, Cerretini, Massimiliano, Tozzi, Fior-Ella, Magnani, Nadia, Cardamone, Giuseppe, Bardicchia, Francesco, Facchi, Edvige, Soscia, Federica, Zotos, Spyridon, Biancosino, Bruno, Zonta, Filippo, Pompei, Francesco, Zizolfi, Daniele, Poloni, Nicola, Ielmini, Marta, Caselli, Ivano, Giana, Edoardo, Buzzi, Aldo, Diurni, Marcello, Milano, Anna, Sani, Emanuele, Calzolari, Roberta, Piccinelli, Marco, Cazzamalli, Sara, Alberini, Gabrio, Piantanida, Silvia, Costantini, Chiara, Paronelli, Chiara, Di Caro, Angela, Moretti, Valentina, Gozzi, Mauro, D'Ippolito, Chiara, Barbanti, Silva Veronica, Alessandro, Papalini, Campese, Ornella, Fiori, Federica, Lorusso, Marco, Di Capro, Lucia, Viceconte, Daniela, Mancini, Valerio, Suraniti, Francesco, Signorelli, Maria Salvina, Rossi, Eugenio, Lupoli, Pasqualino, Menchetti, Marco, Terzi, Laura, Boso, Marianna, Risaro, Paolo, De Paoli, Giuseppe, Catania, Cristina, Tarricone, Ilaria, Caretto, Valentina, Storbini, Viviana, Emiliani, Roberta, Balzarro, Beatrice, Nava, Roberto, Bono, Adele, Provenzi, Milena, Brambilla, Giulia, Aspesi, Flora, Tremolada, Martina, Castagna, Gloria, Bava, Mattia, VERRENGIA, ENRICA, LUCCHI, SARA, Oriani, Maria Ginevra, Barchiesi, Michela, Pacetti, Monica, Magni, Laura Rosa, Rossi, Giuseppe, Beneduce, Rossella, Tura, Giovanni Battista, Laffranchini, Laura, Mastromo, Daniele, Ferrato, Farida, Restaino, Francesco, Monzani, Emiliano, Porcellana, Matteo, Limosani, Ivan, Ghio, Lucio, Ferro, Maurizio, Parise, Vincenzo Fricchione, Balletta, Giovanni, Addeo, Lelio, De Vivo, Elisa, Benedetto, Rossella Di, Pinna, Federica, Carpiniello, Bernardo, Spano, Mariangela, Giacomin, Marzio, Pecile, Damiano, Mattei, Chiara, Fabrici, Elisabetta Pascolo, Panarello, Sofia, Peresson, Giulia, Vitucci, Claudio, Bonavigo, Tommaso, Perini, Giovanni, Boschello, Filippo, Strizzolo, Stefania, Gardellin, Francesco, Di Giannantonio, Massimo, Moretti, Daniele, Fizzotti, Carlo, Cossetta, Edoardo, Gregorio, Luana Di, Sozzi, Francesca, Boncompagni, Giancarlo, Barbera, Daniele La, Colli, Giuseppe, Laurenzi, Sabrina, Calandra, Carmela, Luca, Maria, Ostuzzi, G, Mazzi, M, Terlizzi, S, Bertolini, F, Aguglia, A, Bartoli, F, Bortolaso, P, Callegari, C, Caroleo, M, Carrà, G, Corbo, M, D'Agostino, A, Gastaldon, C, Lucii, C, Magliocco, F, Martinotti, G, Nosé, M, Ostinelli, E, Papola, D, Piccinelli, M, Piccoli, A, Purgato, M, Tabacchi, T, Turrini, G, Ruggeri, M, Barbui, C, De Fazio, P, Raffaele, G, Chirico, M, Cavallotti, S, Bolognesi, S, Debolini, S, Pierantozzi, E, Fargnoli, F, Del Zanna, M, Giannini, A, Luccarelli, L, De Capua, A, Annese, P, Cerretini, M, Tozzi, F, Magnani, N, Cardamone, G, Bardicchia, F, Facchi, E, Soscia, F, Zotos, S, Biancosino, B, Zonta, F, Pompei, F, Zizolfi, D, Poloni, N, Ielmini, M, Caselli, I, Giana, E, Buzzi, A, Diurni, M, Milano, A, Sani, E, Calzolari, R, Cazzamalli, S, Alberini, G, Piantanida, S, Costantini, C, Paronelli, C, Di Caro, A, Moretti, V, Gozzi, M, D'Ippolito, C, Barbanti, S, Alessandro, P, Campese, O, Fiori, F, Lorusso, M, Di Capro, L, Viceconte, D, Mancini, V, Suraniti, F, Signorelli, M, Rossi, E, Lupoli, P, Menchetti, M, Terzi, L, Boso, M, Risaro, P, De Paoli, G, Catania, C, Tarricone, I, Caretto, V, Storbini, V, Emiliani, R, Balzarro, B, Nava, R, Bono, A, Provenzi, M, Brambilla, G, Aspesi, F, Tremolada, M, Castagna, G, Bava, M, Verrengia, E, Lucchi, S, Oriani, M, Barchiesi, M, Pacetti, M, Magni, L, Rossi, G, Beneduce, R, Tura, G, Laffranchini, L, Mastromo, D, Ferrato, F, Restaino, F, Monzani, E, Porcellana, M, Limosani, I, Ghio, L, Ferro, M, Parise, V, Balletta, G, Addeo, L, De Vivo, E, Benedetto, R, Pinna, F, Carpiniello, B, Spano, M, Giacomin, M, Pecile, D, Mattei, C, Fabrici, E, Panarello, S, Peresson, G, Vitucci, C, Bonavigo, T, Perini, G, Boschello, F, Strizzolo, S, Gardellin, F, Di Giannantonio, M, Moretti, D, Fizzotti, C, Cossetta, E, Gregorio, L, Sozzi, F, Boncompagni, G, Barbera, D, Colli, G, Laurenzi, S, Calandra, C, Luca, M, Ostuzzi, Giovanni, Mazzi, Maria Angela, Terlizzi, Samira, Bertolini, Federico, Aguglia, Andrea, Bartoli, Francesco, Bortolaso, Paola, Callegari, Camilla, Caroleo, Mariarita, Carrà, Giuseppe, Corbo, Mariangela, D'Agostino, Armando, Gastaldon, Chiara, Lucii, Claudio, Magliocco, Fabio, Martinotti, Giovanni, Nosé, Michela, Ostinelli, Edoardo Giuseppe, Papola, Davide, Piccinelli, Marco Piero, Piccoli, Alberto, Purgato, Marianna, Tabacchi, Tommaso, Turrini, Giulia, Ruggeri, Mirella, Barbui, Corrado, De Fazio, Pasquale, Raffaele, Gaetano, Chirico, Margherita, Cavallotti, Simone, Bolognesi, Simone, Debolini, Sara, Pierantozzi, Elisa, Fargnoli, Francesco, Del Zanna, Maria, Giannini, Alessandra, Luccarelli, Livia, De Capua, Alberto, Annese, Pasqua Maria, Cerretini, Massimiliano, Tozzi, Fior-Ella, Magnani, Nadia, Cardamone, Giuseppe, Bardicchia, Francesco, Facchi, Edvige, Soscia, Federica, Zotos, Spyridon, Biancosino, Bruno, Zonta, Filippo, Pompei, Francesco, Zizolfi, Daniele, Poloni, Nicola, Ielmini, Marta, Caselli, Ivano, Giana, Edoardo, Buzzi, Aldo, Diurni, Marcello, Milano, Anna, Sani, Emanuele, Calzolari, Roberta, Piccinelli, Marco, Cazzamalli, Sara, Alberini, Gabrio, Piantanida, Silvia, Costantini, Chiara, Paronelli, Chiara, Di Caro, Angela, Moretti, Valentina, Gozzi, Mauro, D'Ippolito, Chiara, Barbanti, Silva Veronica, Alessandro, Papalini, Campese, Ornella, Fiori, Federica, Lorusso, Marco, Di Capro, Lucia, Viceconte, Daniela, Mancini, Valerio, Suraniti, Francesco, Signorelli, Maria Salvina, Rossi, Eugenio, Lupoli, Pasqualino, Menchetti, Marco, Terzi, Laura, Boso, Marianna, Risaro, Paolo, De Paoli, Giuseppe, Catania, Cristina, Tarricone, Ilaria, Caretto, Valentina, Storbini, Viviana, Emiliani, Roberta, Balzarro, Beatrice, Nava, Roberto, Bono, Adele, Provenzi, Milena, Brambilla, Giulia, Aspesi, Flora, Tremolada, Martina, Castagna, Gloria, Bava, Mattia, VERRENGIA, ENRICA, LUCCHI, SARA, Oriani, Maria Ginevra, Barchiesi, Michela, Pacetti, Monica, Magni, Laura Rosa, Rossi, Giuseppe, Beneduce, Rossella, Tura, Giovanni Battista, Laffranchini, Laura, Mastromo, Daniele, Ferrato, Farida, Restaino, Francesco, Monzani, Emiliano, Porcellana, Matteo, Limosani, Ivan, Ghio, Lucio, Ferro, Maurizio, Parise, Vincenzo Fricchione, Balletta, Giovanni, Addeo, Lelio, De Vivo, Elisa, Benedetto, Rossella Di, Pinna, Federica, Carpiniello, Bernardo, Spano, Mariangela, Giacomin, Marzio, Pecile, Damiano, Mattei, Chiara, Fabrici, Elisabetta Pascolo, Panarello, Sofia, Peresson, Giulia, Vitucci, Claudio, Bonavigo, Tommaso, Perini, Giovanni, Boschello, Filippo, Strizzolo, Stefania, Gardellin, Francesco, Di Giannantonio, Massimo, Moretti, Daniele, Fizzotti, Carlo, Cossetta, Edoardo, Gregorio, Luana Di, Sozzi, Francesca, Boncompagni, Giancarlo, Barbera, Daniele La, Colli, Giuseppe, Laurenzi, Sabrina, Calandra, Carmela, and Luca, Maria

Abstract

Background For many years, long-acting intramuscular (LAI) antipsychotics have been prescribed predominantly to chronic and severe patients, as a last resort when other treatments failed. Recently, a broader and earlier use of LAIs, particularly second-generation LAIs, has been emphasized. To date, few studies attempted to frame how this change in prescribing took place in real-world practice. Therefore, this study aimed to describe the clinical features of patients prescribed with LAIs, and to explore possible prescribing differences between first- and second-generations LAIs under ordinary clinical practice in Italy. Methods The STAR Network “Depot” Study is an observational, longitudinal, multicenter study involving 35 centers in Italy. In the cross-sectional phase, patients prescribed with LAIs were consecutively recruited and assessed over a period of 12 months. Descriptive statistics and multivariable logistic regression analyses were employed. Results Of the 451 recruited patients, 61% were males. The level of social and working functioning was heterogeneous, as was the severity of disease. Seventy-two per cent of the patients had a diagnosis of the schizophrenia spectrum. Seventy per cent were prescribed with second-generation antipsychotic (SGA) LAIs (mostly paliperidone, aripiprazole and risperidone). Compared to first-generation antipsychotic (FGA) LAIs, patients prescribed with SGA LAIs were more often younger; employed; with a diagnosis of the schizophrenia spectrum or bipolar disorder; with higher levels of affective symptoms; with fewer LAI prescriptions in the past. Discussion LAIs' prescribing practices appear to be more flexible as compared to the past, although this change is mostly restricted to SGA LAIs.

Published
2018

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