2,281 results on '"Bruzzese A."'
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2. Interactions between Schools and Universities: The Example of Lab2go in Calabria
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Giuseppe Prete, Federica Chiappetta, Piefrancesco Riccardi, Rosanna Tucci, Antonio Bruzzese, and Claudio Meringolo
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Recent research emphasizes the need for a more sustained interaction of schools with universities and research institutions. For example, informal after-school programs integrated into the school curriculum can provide opportunities for meaningful interaction with researchers in active learning settings. At the physics department of University of Calabria it has been launched in 2016 a program aimed at recovering disused, and in several cases ancient, instrumentation in laboratories of some schools in the region of Calabria. In 2022, our local project merged into Lab2go, a national project of the National Institute of Nuclear Physics (INFN) (Lab2go; https://web.infn.it/lab2go/) and of University of Rome "La Sapienza" devoted to the enrichment of the laboratory activities of the schools. Lab2go involves a steadily increasing number of schools and has expanded to include chemistry, robotics and other subjects. This contribution discusses some didactic activities developed within Lab2go. The activities of Lab2go are integrated and form part of the (formal) school curriculum as work based experiences, which have become mandatory during the last three years of secondary schools. Thus, this project is an example of how specific policy interventions can lead to the kind of long-term structured collaboration between schools and research institutions needed to favor the shift of focus in science education. [For the full proceedings, see ED656038.]
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- 2023
3. Maternal hypercholesterolaemia during pregnancy affects severity of myocardial infarction in young adults
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Cacciatore, F, Bruzzese, G, Abete, P, Russo, G, Palinski, W, and Napoli, C
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Health Sciences ,Good Health and Well Being - Published
- 2023
4. Randomized phase 2 study of valproic acid combined with simvastatin and gemcitabine/nab-paclitaxel-based regimens in untreated metastatic pancreatic adenocarcinoma patients: the VESPA trial study protocol
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Budillon, Alfredo, Leone, Alessandra, Passaro, Eugenia, Silvestro, Lucrezia, Foschini, Francesca, Iannelli, Federica, Roca, Maria Serena, Macchini, Marina, Bruzzese, Francesca, Garcia Bermejo, Maria Laura, Rodriguez Garrote, Mercedes, Tortora, Giampaolo, Milella, Michele, Reni, Michele, Fuchs, Claudia, Hewitt, Eve, Kubiak, Christine, Di Gennaro, Elena, Giannarelli, Diana, and Avallone, Antonio
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- 2024
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5. Identification and characterization of a new potent inhibitor targeting CtBP1/BARS in melanoma cells
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Filograna, Angela, De Tito, Stefano, Monte, Matteo Lo, Oliva, Rosario, Bruzzese, Francesca, Roca, Maria Serena, Zannetti, Antonella, Greco, Adelaide, Spano, Daniela, Ayala, Inmaculada, Liberti, Assunta, Petraccone, Luigi, Dathan, Nina, Catara, Giuliana, Schembri, Laura, Colanzi, Antonino, Budillon, Alfredo, Beccari, Andrea Rosario, Del Vecchio, Pompea, Luini, Alberto, Corda, Daniela, and Valente, Carmen
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- 2024
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6. Identification and characterization of a new potent inhibitor targeting CtBP1/BARS in melanoma cells
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Angela Filograna, Stefano De Tito, Matteo Lo Monte, Rosario Oliva, Francesca Bruzzese, Maria Serena Roca, Antonella Zannetti, Adelaide Greco, Daniela Spano, Inmaculada Ayala, Assunta Liberti, Luigi Petraccone, Nina Dathan, Giuliana Catara, Laura Schembri, Antonino Colanzi, Alfredo Budillon, Andrea Rosario Beccari, Pompea Del Vecchio, Alberto Luini, Daniela Corda, and Carmen Valente
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C-terminal Binding Protein (CtBP) ,Rossmann fold ,Benzenesulfonamide ,CtBP inhibitor ,Melanoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The C-terminal-binding protein 1/brefeldin A ADP-ribosylation substrate (CtBP1/BARS) acts both as an oncogenic transcriptional co-repressor and as a fission inducing protein required for membrane trafficking and Golgi complex partitioning during mitosis, hence for mitotic entry. CtBP1/BARS overexpression, in multiple cancers, has pro-tumorigenic functions regulating gene networks associated with “cancer hallmarks” and malignant behavior including: increased cell survival, proliferation, migration/invasion, epithelial-mesenchymal transition (EMT). Structurally, CtBP1/BARS belongs to the hydroxyacid-dehydrogenase family and possesses a NAD(H)-binding Rossmann fold, which, depending on ligands bound, controls the oligomerization of CtBP1/BARS and, in turn, its cellular functions. Here, we proposed to target the CtBP1/BARS Rossmann fold with small molecules as selective inhibitors of mitotic entry and pro-tumoral transcriptional activities. Methods Structured-based screening of drug databases at different development stages was applied to discover novel ligands targeting the Rossmann fold. Among these identified ligands, N-(3,4-dichlorophenyl)-4-{[(4-nitrophenyl)carbamoyl]amino}benzenesulfonamide, called Comp.11, was selected for further analysis. Fluorescence spectroscopy, isothermal calorimetry, computational modelling and site-directed mutagenesis were employed to define the binding of Comp.11 to the Rossmann fold. Effects of Comp.11 on the oligomerization state, protein partners binding and pro-tumoral activities were evaluated by size-exclusion chromatography, pull-down, membrane transport and mitotic entry assays, Flow cytometry, quantitative real-time PCR, motility/invasion, and colony assays in A375MM and B16F10 melanoma cell lines. Effects of Comp.11 on tumor growth in vivo were analyzed in mouse tumor model. Results We identify Comp.11 as a new, potent and selective inhibitor of CtBP1/BARS (but not CtBP2). Comp.11 directly binds to the CtBP1/BARS Rossmann fold affecting the oligomerization state of the protein (unlike other known CtBPs inhibitors), which, in turn, hinders interactions with relevant partners, resulting in the inhibition of both CtBP1/BARS cellular functions: i) membrane fission, with block of mitotic entry and cellular secretion; and ii) transcriptional pro-tumoral effects with significantly hampered proliferation, EMT, migration/invasion, and colony-forming capabilities. The combination of these effects impairs melanoma tumor growth in mouse models. Conclusions This study identifies a potent and selective inhibitor of CtBP1/BARS active in cellular and melanoma animal models revealing new opportunities to study the role of CtBP1/BARS in tumor biology and to develop novel melanoma treatments.
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- 2024
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7. Recommendations for recognizing, risk stratifying, treating, and managing children and adolescents with hypoglycemia
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Stefano Zucchini, Stefano Tumini, Andrea Enzo Scaramuzza, Riccardo Bonfanti, Maurizio Delvecchio, Roberto Franceschi, Dario Iafusco, Lorenzo Lenzi, Enza Mozzillo, Stefano Passanisi, Claudia Piona, Ivana Rabbone, Novella Rapini, Andrea Rigamonti, Carlo Ripoli, Giuseppina Salzano, Silvia Savastio, Riccardo Schiaffini, Angela Zanfardino, Valentino Cherubini, Diabetes Study Group of the Italian Society for Pediatric Endocrinology Diabetes, Albino Claudia Accursia, Aloe Monica, Anzelotti Maria Teresa, Arnaldi Claudia, Barbetti Fabrizio, Bassi Marta, Berioli Maria Giulia, Bernardini Luca, Bertelli Enrica, Biagioni Martina, Bobbio Adriana, Bombaci Bruno, Bonfanti Riccardo, Bonura Clara, Bracciolini Giulia Patrizia, Bruzzese Mariella, Bruzzi Patrizia, Buono Pietro, Buscarino Piera, Cadario Francesco, Calcaterra Valeria, Calzi Elena, Cappa Marco, Cardani Roberta, Cardella Francesca, Cardinale Giuliana Marcella, Casertano Alberto, Castorani Valeria, Cauvin Vittoria, Cenciarelli Valentina, Ceruti Franco, Cherubini Valentino, Chiarelli Francesco, Chiari Giovanni, Cianfarani Stefano, Cicchetti Mario, Cipriano Paola, Cirillo Dante, Citriniti Felice, Coccioli Maria Susanna, Confetto Santino, Contreas Giovanna, Coro Anna, Correddu Antonella, Corsini Elisa, Crino’ Antonino, d’Annunzio Giuseppe, De Berardinis Fiorella, De Donno Valeria, De Filippo Gianpaolo, De Marco Rosaria, De Sanctis Luisa, Del Duca Elisabetta, Delvecchio Maurizio, Deodati Annalisa, Di Bonito Procolo, Di Candia Francesca, Faleschini Elena, Fattorusso Valentina, Favia Anna, Federico Giovanni, Felappi Barbara, Ferrari Mara, Ferrito Lucia, Fichera Graziella, Fontana Franco, Fornari Elena, Franceschi Roberto, Franco Francesca, Franzese Adriana, Frongia Anna Paola, Frontino Giulio, Gaiero Alberto, Galassi Sabrina Maria, Gallo Francesco, Gargantini Luigi, Giani Elisa, Gortan Anna Jolanda, Graziani Vanna, Grosso Caterina, Gualtieri Antonella, Guasti Monica, Guerraggio Lucia Paola, Guzzetti Chiara, Iafusco Dario, Iannicelli Gennaro, Iezzi Maria Laura, Ignaccolo Maria Giovanna, Innaurato Stefania, Inzaghi Elena, Iovane Brunella, Iughetti Lorenzo, Kaufmann Peter, La Loggia Alfonso, Lambertini Anna Giulia, Lapolla Rosa, Lasagni Anna, Lazzaro Nicola, Lazzeroni Pietro, Lenzi Lorenzo, Lera Riccardo, Levantini Gabriella, Lezzi Marilea, Lia Rosanna, Liguori Alice, Lo Presti Donatella, Lombardo Fortunato, Lonero Antonella, Longhi Silvia, Lorubbio Antonella, Lucchesi Sonia, Maccioni Rosella, Macedoni Maddalena, Macellaro Patrizia Cristiana, Madeo Simona Filomena, Maffeis Claudio, Mainetti Benedetta, Maltoni Giulio, Mameli Chiara, Mammì Francesco, Manca Bitti Maria Luisa, Mancioppi Valentina, Manco Melania, Marigliano Marco, Marino Monica, Marsciani Alberto, Matteoli Maria Cristina, Mazzali Elena, Minute Marta, Minuto Nicola, Monti Sara, Morandi Anita,, Morganti Gianfranco, Morotti Elisa, Mozzillo Enza, Musolino Gianluca, Olivieri Francesca, Ortolani Federica, Pampanini Valentina, Pardi Daniela, Pascarella Filomena, Pasquino Bruno, Passanisi Stefano, Patera Ippolita Patrizia, Pedini Annalisa, Pennati Maria Cristina, Peruzzi Sonia, Peverelli Paola, Pezzino Giulia, Piccini Barbara, Piccinno Elvira Eugenia Rosaria, Piona Claudia, Piredda Gavina, Piscopo Alessia, Pistone Carmelo, Pozzi Erica, Prandi Elena, Predieri Barbara, Prudente Sabrina, Pulcina Anna, Rabbone Ivana, Randazzo Emioli, Rapini Novella, Reinstadler Petra, Riboni Sara, Ricciardi Maria Rossella, Rigamonti Andrea, Ripoli Carlo, Rossi Virginia, Rossi Paolo, Rutigliano Irene, Sabbion Alberto, Salvatoni Alessandro, Salvo Caterina, Salzano Giuseppina, Sanseviero Mariateresa, Savastio Silvia, Savini Rosanna, Scanu Mariapiera, Scaramuzza Andrea Enzo, Schiaffini Riccardo, Schiavone Maurizio, Schieven Eleonardo, Scipione Mirella, Secco Andrea, Silvestri Francesca, Siri Giulia, Sogno Valin Paola, Sordelli Silvia, Spiri Daniele, Stagi Stefano, Stamati Filomena Andreina, Suprani Tosca, Talarico Valentina, Tiberi Valentina, Timpanaro Tiziana Antonia Lucia, Tinti Davide, Tirendi Antonina, Tomaselli Letizia Grazia, Toni Sonia, Torelli Cataldo, Tornese Gianluca, Trada Michela,, Trettene Adolfo Andrea, Tumini Stefano, Tumminelli Marilena, Valerio Giuliana, Vandelli Sara, Ventrici Claudia, Zampolli Maria, Zanatta Manuela, Zanfardino Angela, Zecchino Clara, Zonca Silvia, and Zucchini Stefano
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adolescents ,automated insulin delivery ,children ,hypoglycemia ,glucagon ,oral glucose ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
There has been continuous progress in diabetes management over the last few decades, not least due to the widespread dissemination of continuous glucose monitoring (CGM) and automated insulin delivery systems. These technological advances have radically changed the daily lives of people living with diabetes, improving the quality of life of both children and their families. Despite this, hypoglycemia remains the primary side-effect of insulin therapy. Based on a systematic review of the available scientific evidence, this paper aims to provide evidence-based recommendations for recognizing, risk stratifying, treating, and managing patients with hypoglycemia. The objective of these recommendations is to unify the behavior of pediatric diabetologists with respect to the timely recognition and prevention of hypoglycemic episodes and the correct treatment of hypoglycemia, especially in patients using CGM or advanced hybrid closed-loop systems. All authors have long experience in the specialty and are members of the Italian Society of Pediatric Endocrinology and Diabetology. The goal of treating hypoglycemia is to raise blood glucose above 70 mg/dL (3.9 mmol/L) and to prevent further decreases. Oral glucose at a dose of 0.3 g/kg (0.1 g/kg for children using “smart pumps” or hybrid closed loop systems in automated mode) is the preferred treatment for the conscious individual with blood glucose
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- 2024
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8. Sodium-glucose cotransporter 2 inhibitor dapagliflozin prevents ejection fraction reduction, reduces myocardial and renal NF-κB expression and systemic pro-inflammatory biomarkers in models of short-term doxorubicin cardiotoxicity
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V. Quagliariello, M. L. Canale, I. Bisceglia, M. Iovine, A. Paccone, C. Maurea, M. Scherillo, A. Merola, V. Giordano, G. Palma, A. Luciano, F. Bruzzese, F. Zito Marino, M. Montella, R. Franco, M. Berretta, D. Gabrielli, G. Gallucci, and N. Maurea
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cancer ,dapagliflozin ,cardio-oncology ,cardioprotection ,doxorubicin ,NF-kB ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundAnthracycline-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in patients with cancer. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exert multiple cardiometabolic benefits in patients with/without type 2 diabetes, chronic kidney disease, and heart failure with reduced and preserved ejection fraction. We hypothesized that the SGLT2i dapagliflozin administered before and during doxorubicin (DOXO) therapy could prevent cardiac dysfunction and reduce pro-inflammatory pathways in preclinical models.MethodsCardiomyocytes were exposed to DOXO alone or combined with dapagliflozin (DAPA) at 10 and 100 nM for 24 h; cell viability, iATP, and Ca++ were quantified; lipid peroxidation products (malondialdehyde and 4-hydroxy 2-hexenal), NLRP3, MyD88, and cytokines were also analyzed through selective colorimetric and enzyme-linked immunosorbent assay (ELISA) methods. Female C57Bl/6 mice were treated for 10 days with a saline solution or DOXO (2.17 mg/kg), DAPA (10 mg/kg), or DOXO combined with DAPA. Systemic levels of ferroptosis-related biomarkers, galectin-3, high-sensitivity C-reactive protein (hs-CRP), and pro-inflammatory chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified. After treatments, immunohistochemical staining of myocardial and renal p65/NF-kB was performed.ResultsDAPA exerts cytoprotective, antioxidant, and anti-inflammatory properties in human cardiomyocytes exposed to DOXO by reducing iATP and iCa++ levels, lipid peroxidation, NLRP-3, and MyD88 expression. Pro-inflammatory intracellular cytokines were also reduced. In preclinical models, DAPA prevented the reduction of radial and longitudinal strain and ejection fraction after 10 days of treatment with DOXO. A reduced myocardial expression of NLRP-3 and MyD-88 was seen in the DOXO-DAPA group compared to DOXO mice. Systemic levels of IL-1β, IL-6, TNF-α, G-CSF, and GM-CSF were significantly reduced after treatment with DAPA. Serum levels of galectine-3 and hs-CRP were strongly enhanced in the DOXO group; on the other hand, their expression was reduced in the DAPA-DOXO group. Troponin-T, B-type natriuretic peptide (BNP), and N-Terminal Pro-BNP (NT-pro-BNP) were strongly reduced in the DOXO-DAPA group, revealing cardioprotective properties of SGLT2i. Mice treated with DOXO and DAPA exhibited reduced myocardial and renal NF-kB expression.ConclusionThe overall picture of the study encourages the use of DAPA in the primary prevention of cardiomyopathies induced by anthracyclines in patients with cancer.
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- 2024
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9. Spontaneous cancer remission after COVID-19: insights from the pandemic and their relevance for cancer treatment
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Meo, Concetta, Palma, Giuseppe, Bruzzese, Francesca, Budillon, Alfredo, Napoli, Claudio, and de Nigris, Filomena
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- 2023
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10. The role of long-acting antipsychotics in illness relapse: an observational study
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I. Berardelli, I. Mancinelli, E. Rogante, D. Erbuto, M. A. Trocchia, L. Longhini, L. Rapisarda, A. Bruzzese, S. Sarubbi, and M. Pompili
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Psychiatry ,RC435-571 - Abstract
Introduction In patients affected by Schizophrenia and Bipolar Disorder disorders the use of antipsychotic drugs is essential in preventing the exacerbation of symptoms. The use of long-acting injectable (LAI) antipsychotics is considered an important treatment option. The aim of this study was to evaluate the incidence and predictors of relapse during antipsychotic treatment with LAIs in a sample of psychiatric outpatients up to a year after the start of long-acting therapy. Objectives The study included 103 adult patients admitted to the psychiatric unit of Sant’Andrea University Hospital in Rome. Methods We evaluated duration of untreated illness, previous treatments, substance abuse, suicidal status, LAI dose, and use of other medicines for association with new episodes of illness or of symptomatic worsening as well as hospitalization, using bivariate and multivariate analyses. Results Seventy-three patients were diagnosed with schizophrenia spectrum and 30 with bipolar disorders. Age at study entry averaged 36.7 years (SD= 11.55). 40.8% of patients were women. The mean age at onset were 23.11 (SD= 7.0). All the other information were reported in Table 1. On 103 patients undergoing with LAI treatment for a year only 9 (8.7%) patients had a relapse during the study period. The two groups differed according to the presence of hospitalization during the 12 months before the LAI treatment (p = .022), in particular patients with relapse were more hospitalized than patients with no relapse (62.5% vs. 21.7%). Moreover, group with relapse were more at risk of suicide during the 12 months before the LAI treatment than the other group, for both suicidal ideation (11.1% vs. 4.3%; p= .015) and attempt (25.0% vs. 3.2%; p= .049). Finally, the two groups differed according to the side effects reported during the year of LAI treatment (χ² =38.48; p< .001). Specifically, patients’ group with relapse reported more side effects caused by parkinsonism (25.0% vs. 1.1%) and tremor (25.0% vs. 0%). No differences were found for the other variables (See table 1). Image: Conclusions In conclusion, our observations confirm the importance of LAI therapy in real word. However, our results indicate that these drugs might not prevent subsequent exacerbations for a proportion of individuals whose illness is stabilised on continuous antipsychotic treatment. Extra pyramidal symptoms in particular might have pathophysiological implications for relapse. Disclosure of Interest None Declared
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- 2024
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11. Circulating cytokines and risk of developing hypertension: A systematic review and meta-analysis
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Elisabetta Caiazzo, Malvika Sharma, Asma O.M. Rezig, Moustafa I. Morsy, Marta Czesnikiewicz-Guzik, Armando Ialenti, Joanna Sulicka-Grodzicka, Pierpaolo Pellicori, Simone H. Crouch, Aletta E. Schutte, Dario Bruzzese, Pasquale Maffia, and Tomasz J. Guzik
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Cytokines ,Incident hypertension ,Risk ,Systematic review ,Meta-analysis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: Immune responses play a significant role in hypertension, though the importance of key inflammatory mediators remains to be defined. We used a systematic literature review and meta-analysis to study the associations between key cytokines and incident hypertension. Methods: We performed a systematic search of Pubmed/Medline, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL), for peer-reviewed studies published up to August 2022. Incident hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg and/or the use of antihypertensive medications. Random effects meta-analyses were used to calculate pooled hazard ratios (HRs)/risk ratios (RRs) and 95% confidence intervals by cytokine levels (highest vs. lowest quartile). Results: Only IL-6 and IL-1β levels have evidence allowing for quantitative evaluation concerning the onset of hypertension. Six studies (10406 participants, 2932 incident cases) examined the association of IL-6 with incident hypertension. The highest versus lowest quartile of circulating IL-6 was associated with a significant HR/RR of hypertension (1.61, 95% CI: 1.00 to 2.60; I2 =87%). After adjusting for potential confounders, including body mass index (BMI), HR/RR was no longer significant (HR/RR: 1.24; 95% CI, 0.96 to 1.61; I2 = 56%). About IL-1β, neither the crude (HR/RR: 1.03; 95% CI, 0.60 to 1.76; n = 2) nor multivariate analysis (HR/RR: 0.97, 95% CI, 0.60 to 1.56; n = 2) suggested a significant association with the risk of developing hypertension. Conclusions: A limited number of studies suggest that higher IL-6, but not IL-1β, might be associated with the development of hypertension.
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- 2024
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12. β2-AR inhibition enhances EGFR antibody efficacy hampering the oxidative stress response machinery
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Vitale Del Vecchio, Luigi Mele, Sameer Kumar Panda, Ibone Rubio Sanchez-Pajares, Laura Mosca, Virginia Tirino, Massimiliano Barbieri, Francesca Bruzzese, Antonio Luciano, Federica Zito Marino, Marina Accardo, Giovanni Francesco Nicoletti, Gianpaolo Papaccio, Antonio Barbieri, and Vincenzo Desiderio
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Cytology ,QH573-671 - Abstract
Abstract The β2-Adrenergic receptor (β2-ARs) is a cell membrane-spanning G protein-coupled receptors (GPCRs) physiologically involved in stress-related response. In many cancers, the β2-ARs signaling drives the tumor development and transformation, also promoting the resistance to the treatments. In HNSCC cell lines, the β2-AR selective inhibition synergistically amplifies the cytotoxic effect of the MEK 1/2 by affecting the p38/NF-kB oncogenic pathway and contemporary reducing the NRF-2 mediated antioxidant cell response. In this study, we aimed to validate the anti-tumor effect of β2-AR blockade and the synergism with MEK/ERK and EGFR pathway inhibition in a pre-clinical orthotopic mouse model of HNSCC. Interestingly, we found a strong β2-ARs expression in the tumors that were significantly reduced after prolonged treatment with β2-Ars inhibitor (ICI) and EGFR mAb Cetuximab (CTX) in combination. The β2-ARs down-regulation correlated in mice with a significant tumor growth delay, together with the MAPK signaling switch-off caused by the blockade of the MEK/ERK phosphorylation. We also demonstrated that the administration of ICI and CTX in combination unbalanced the cell ROS homeostasis by blocking the NRF-2 nuclear translocation with the relative down-regulation of the antioxidant enzyme expression. Our findings highlighted for the first time, in a pre-clinical in vivo model, the efficacy of the β2-ARs inhibition in the treatment of the HNSCC, remarkably in combination with CTX, which is the standard of care for unresectable HNSCC.
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- 2023
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13. Circulating cytokines and risk of developing hypertension: A systematic review and meta-analysis
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Caiazzo, Elisabetta, Sharma, Malvika, Rezig, Asma O.M., Morsy, Moustafa I., Czesnikiewicz-Guzik, Marta, Ialenti, Armando, Sulicka-Grodzicka, Joanna, Pellicori, Pierpaolo, Crouch, Simone H., Schutte, Aletta E., Bruzzese, Dario, Maffia, Pasquale, and Guzik, Tomasz J.
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- 2024
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14. Influence of Safety Warnings on the Prescribing Attitude of JAK Inhibitors for Rheumatoid Arthritis in Italy
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Marino Paroli, Andrea Becciolini, Alberto Lo Gullo, Simone Parisi, Elena Bravi, Romina Andracco, Valeria Nucera, Francesca Ometto, Federica Lumetti, Antonella Farina, Patrizia Del Medico, Matteo Colina, Viviana Ravagnani, Palma Scolieri, Maddalena Larosa, Marta Priora, Elisa Visalli, Olga Addimanda, Rosetta Vitetta, Alessandro Volpe, Alessandra Bezzi, Francesco Girelli, Aldo Biagio Molica Colella, Rosalba Caccavale, Eleonora Di Donato, Giuditta Adorni, Daniele Santilli, Gianluca Lucchini, Eugenio Arrigoni, Ilaria Platè, Natalia Mansueto, Aurora Ianniello, Enrico Fusaro, Maria Chiara Ditto, Vincenzo Bruzzese, Dario Camellino, Gerolamo Bianchi, Francesca Serale, Rosario Foti, Giorgio Amato, Francesco De Lucia, Ylenia Dal Bosco, Roberta Foti, Massimo Reta, Alessia Fiorenza, Guido Rovera, Antonio Marchetta, Maria Cristina Focherini, Fabio Mascella, Simone Bernardi, Gilda Sandri, Dilia Giuggioli, Carlo Salvarani, Maria Ilenia De Andres, Veronica Franchina, Francesco Molica Colella, Giulio Ferrero, Bernd Raffeiner, and Alarico Ariani
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janus kinase inhibitors ,safety warnings ,prescribing attitude ,rheumatoid arthritis ,Medicine - Abstract
Background/Objectives: The Janus kinase inhibitors (JAKi) tofacitinib (TOFA), baricitinib (BARI), upadacitinib (UPA), and filgotinib (FILGO) are effective drugs for the treatment of rheumatoid arthritis. However, the US Food and Drug Administration (FDA) raised concerns about the safety of TOFA after its approval. This prompted the European Medicines Agency (EMA) to issue two safety warnings for limiting TOFA use, then extended a third warning to all JAKi in patients at high risk of developing serious adverse effects (SAE). These include thrombosis, major adverse cardiac events (MACE), and cancer. The purpose of this work was to analyze how the first two safety warnings from the EMA affected the prescribing of JAKi by rheumatologists in Italy. Methods: All patients with rheumatoid arthritis who had been prescribed JAKi for the first time in a 36-month period from 1 July 2019, to 30 June 2022 were considered. Data were obtained from the medical records of 29 Italian tertiary referral rheumatology centers. Patients were divided into three groups of 4 months each, depending on whether the JAKi prescription had occurred before the EMA’s first safety alert (1 July–31 October 2019, Group 1), between the first and second alerts (1 November 2019–29 February 2020, Group 2), or between the second and third alerts (1 March 2021–30 June 2021, Group 3). The percentages and absolute changes in the patients prescribed the individual JAKi were analyzed. Differences among the three groups of patients regarding demographic and clinical characteristics were also assessed. Results: A total of 864 patients were prescribed a JAKi during the entire period considered. Of these, 343 were identified in Group 1, 233 in Group 2, and 288 in Group 3. An absolute reduction of 32% was observed in the number of patients prescribed a JAKi between Group 1 and Group 2 and 16% between Group 1 and Group 3. In contrast, there was a 19% increase in the prescription of a JAKi in patients between Group 2 and Group 3. In the first group, BARI was the most prescribed drug (227 prescriptions, 66.2% of the total), followed by TOFA (115, 33.5%) and UPA (1, 0.3%). In the second group, the most prescribed JAKi was BARI (147, 63.1%), followed by TOFA (65, 27.9%) and UPA (33, 11.5%). In the third group, BARI was still the most prescribed JAKi (104 prescriptions, 36.1%), followed by UPA (89, 30.9%), FILGO (89, 21.5%), and TOFA (33, 11.5%). The number of patients prescribed TOFA decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). The number of patients who were prescribed BARI decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). In contrast, the number of patients prescribed UPA increased between Group 2 and Group 3 (p ˂ 0.01). Conclusions: These data suggest that the warnings issued for TOFA were followed by a reduction in total JAKi prescriptions. However, the more selective JAKi (UPA and FILGO) were perceived by prescribers as favorable in terms of the risk/benefit ratio, and their use gradually increased at the expense of the other molecules.
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- 2024
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15. Analysis of survival rate and persistence predictors of baricitinib in real-world data from a large cohort of rheumatoid arthritis patients
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Parisi, Simone, Andrea, Becciolini, Chiara, Ditto Maria, Lo Gullo, Alberto, Maddalena, Larosa, Palma, Scolieri, Olga, Addimanda, Massimo, Reta, Paroli, Marino, Rosalba, Caccavale, Elisa, Visalli, Rosario, Foti, Giorgio, Amato, Francesco, De Lucia, Ylenia, Dal Bosco, Roberta, Foti, Antonella, Farina, Francesco, Girelli, Simone, Bernardi, Dario, Camellino, Gerolamo, Bianchi, Matteo, Colina, Romina, Andracco, Natalia, Mansueto, Giulio, Ferrero, Patrizia, Del Medico, Aldo, Molica Colella, Veronica, Franchina, Francesco, Molica Colella, Federica, Lumetti, Gilda, Sandri, Carlo, Salvarani, Marta, Priora, Aurora, Ianniello, Valeria, Nucera, Daniele, Santilli, Gianluca, Lucchini, Adorni, Giuditta, Eleonora, Di Donato, Elena, Bravi, Ilaria, Platè, Eugenio, Arrigoni, Alessandra, Bezzi, Cristina, Focherini Maria, Fabio, Mascella, Vincenzo, Bruzzese, Viviana, Ravagnani, Alessia, Fiorenza, Guido, Rovera, Rosetta, Vitetta, Antonio, Marchetta, Alessandro, Volpe, Francesca, Ometto, Alarico, Ariani, and Enrico, Fusaro
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- 2024
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16. Safe and Effective Administration of Caplacizumab in COVID-19-Associated Thrombotic Thrombocytopenic Purpura
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Antonella Bruzzese, Ernesto Vigna, Dario Terzi, Sonia Greco, Enrica Antonia Martino, Valeria Vangeli, Francesco Mendicino, Eugenio Lucia, Virginia Olivito, Caterina Labanca, Rosellina Morelli, Antonino Neri, Fortunato Morabito, Francesco Zinno, Antonio Mastroianni, and Massimo Gentile
- Subjects
COVID-19 ,TTP ,caplacizumab ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Thrombotic thrombocytopenic purpura (TTP) is a potentially life-threatening, rare acute thrombotic microangiopathy (TMA), caused by a severe ADAMTS13 deficiency. As the COVID-19 pandemic rapidly spread around the globe, much data about the pathogenicity of this virus were published. Soon after the detection of the first cases of COVID-19, it was clear that there was a wide range of COVID coagulopathy manifestations, such as deep venous thrombosis, pulmonary thromboembolism, and thrombotic microangiopathies. In the literature, little data have been reported about the association between TTP and COVID-19, and the treatment of COVID-19-associated TTP is still under debate. Here we present the case of a 46-year-old woman who developed a COVID-associated TTP, successfully treated with plasma exchange (PEX), steroids, and caplacizumab.
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- 2023
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17. Is the Number of Citations Related to the Study Methodology in Shoulder Arthroplasty Literature? A Bibliometric and Statistical Analysis of Current Evidence
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Roberto de Giovanni, Amedeo Guarino, Valentina Rossi, Dario Bruzzese, Massimo Mariconda, and Andrea Cozzolino
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Orthopedic surgery ,RD701-811 - Abstract
Background We reviewed the shoulder arthroplasty (SA) literature to correlate citations, methodological characteristics and quality of most-cited articles in this field. We hypothesized that a greater number of citations would be found for high-quality clinical studies. Methods We searched the Web of Knowledge database for the 50 most-cited articles about SA and collected author name, publication year, country of origin, journal, article type, level of evidence (LoE), subject of paper, type of arthroplasty and metrics (number of citations and citation rate). Coleman Methodology Score (CMS) was computed for clinical articles. Statistical analysis of variance and correlation coefficients were used to investigate the relationship between different variables. Results Out of the selected 50 studies on SA, 26% were nonclinical. There were 15,393 citations overall (mean 307.8), with a mean 19.5 citations per year (range 48.3-6.7). Thirty or 60% of all articles were LoE IV. All studies were published between 1984 and 2011 in 8 journals. Reverse SA (RSA) was the most common subject (36% of studies). The United States was the country responsible for most contributions (50% of studies). CMS ranged from 81 to 38 (mean 59.6). RSA received the highest number of citations ( P
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- 2024
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18. Analysis of survival rate and persistence predictors of baricitinib in real-world data from a large cohort of rheumatoid arthritis patients
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Simone Parisi, Becciolini Andrea, Ditto Maria Chiara, Alberto Lo Gullo, Larosa Maddalena, Scolieri Palma, Addimanda Olga, Reta Massimo, Marino Paroli, Caccavale Rosalba, Visalli Elisa, Foti Rosario, Amato Giorgio, De Lucia Francesco, Dal Bosco Ylenia, Foti Roberta, Farina Antonella, Girelli Francesco, Bernardi Simone, Camellino Dario, Bianchi Gerolamo, Colina Matteo, Andracco Romina, Mansueto Natalia, Ferrero Giulio, Del Medico Patrizia, Molica Colella Aldo, Franchina Veronica, Molica Colella Francesco, Lumetti Federica, Sandri Gilda, Salvarani Carlo, Priora Marta, Ianniello Aurora, Nucera Valeria, Santilli Daniele, Lucchini Gianluca, Giuditta Adorni, Di Donato Eleonora, Bravi Elena, Platè Ilaria, Arrigoni Eugenio, Bezzi Alessandra, Focherini Maria Cristina, Mascella Fabio, Bruzzese Vincenzo, Ravagnani Viviana, Fiorenza Alessia, Rovera Guido, Vitetta Rosetta, Marchetta Antonio, Volpe Alessandro, Ometto Francesca, Ariani Alarico, and Fusaro Enrico
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JAK inhibitors ,tsDMARD ,bDMARD ,Rheumatoid arthritis ,Survival rate ,Baricitinib ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Objectives: The persistence in therapy of rheumatoid arthritis drugs and particularly bDMARD is a limiting factor for their long-term use. The randomized controlled trials (RCTs) may not reflect real-world contexts due to strict inclusion and exclusion criteria. Baricitinib, which targets both JAK1 and JAK2, has been used in Italy for several years. The aim of this multi-center study is to assess the real world persistence on therapy of baricitinib in RA patients and to identify predictive factors of baricitinib's survival rate. Methods: This is a retrospective, multicentric, Italian, longitudinal study. All patients were enrolled according to the following criteria: a) age ≥ 18 years old; b) diagnosed with RA according 2010 ACR/EULAR classification criteria; c) treated with baricitinib. In order to describe baricitinib clinical efficacy, the survival rate was evaluated by The Kaplan–Meier curve. Then, predictive factors of drug retention rate were assessed by performing the Cox analysis, identifying which risk factors influenced treatment persistence. Results: Overall, we included 478 patients treated with baricitinib. Among them, 380 (79.5%) were females. Baricitinib's survival rate was 94.6% at 6 months, 87.9% at 12 months, 81.7% at 24 months and 53.4% at 48 months. The Cox analysis regression showed that a higher bDMARDs/tsDMARD line of therapy seems to be a negative prognostic factor for the drug retention rate (HR 1.26 CI 95% 1.07–1.49, p = 0.006. Conclusion: Real-life study confirms baricitinib effectiveness up to 4 years, but previous treatment with bDMARDs was a negative prognostic factor for its survival rate.
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- 2024
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19. Using a mobile nanopore sequencing lab for end-to-end genomic surveillance of Plasmodium falciparum: A feasibility study.
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Aurel Holzschuh, Anita Lerch, Bakar S Fakih, Safia Mohammed Aliy, Mohamed Haji Ali, Mohamed Ali Ali, Daniel J Bruzzese, Joshua Yukich, Manuel W Hetzel, and Cristian Koepfli
- Subjects
Public aspects of medicine ,RA1-1270 - Abstract
Genomic epidemiology holds promise for malaria control and elimination efforts, for example by informing on Plasmodium falciparum genetic diversity and prevalence of mutations conferring anti-malarial drug resistance. Limited sequencing infrastructure in many malaria-endemic areas prevents the rapid generation of genomic data. To address these issues, we developed and validated assays for P. falciparum nanopore sequencing in endemic sites using a mobile laboratory, targeting key antimalarial drug resistance markers and microhaplotypes. Using two multiplexed PCR reactions, we amplified six highly polymorphic microhaplotypes and ten drug resistance markers. We developed a bioinformatics workflow that allows genotyping of polyclonal malaria infections, including minority clones. We validated the panels on mock dried blood spot (DBS) and rapid diagnostic test (RDT) samples and archived DBS, demonstrating even, high read coverage across amplicons (range: 580x to 3,212x median coverage), high haplotype calling accuracy, and the ability to explore within-sample diversity of polyclonal infections. We field-tested the feasibility of rapid genotyping in Zanzibar in close collaboration with the local malaria elimination program using DBS and routinely collected RDTs as sample inputs. Our assay identified haplotypes known to confer resistance to known antimalarials in the dhfr, dhps and mdr1 genes, but no evidence of artemisinin partial resistance. Most infections (60%) were polyclonal, with high microhaplotype diversity (median HE = 0.94). In conclusion, our assays generated actionable data within a few days, and we identified current challenges for implementing nanopore sequencing in endemic countries to accelerate malaria control and elimination.
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- 2024
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20. Depressive symptoms are related to asthma control but not self-management among rural adolescents
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Neha B. Patel, Amarilis Céspedes, Jianfang Liu, and Jean-Marie Bruzzese
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adolescents ,asthma ,comorbid ,depression ,mental health ,non-urban ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundDepression, a relevant comorbidity with asthma, has been reported to be associated with asthma morbidity. Asthma self-management is essential to asthma control and may be negatively impacted by depression. We examined these associations in rural adolescents, a group with relatively high asthma morbidity and depressive symptoms, a population often ignored in asthma research.MethodsWe used baseline data from a randomized trial of an asthma intervention for adolescents in rural South Carolina (n = 197). Adolescents completed the Center for Epidemiological Studies-Depression (CES-D), three indices of asthma self-management (the Asthma Prevention Index, the Asthma Management Index and the Asthma Self-Efficacy Index), and the Asthma Control Test (ACT). Poisson and linear regression tested associations between depression, self-management, and asthma control. The models controlled for demographic variables and included school as a fixed effect.ResultsMost participants (mean age = 16.3 ± 1.2 years) self-identified as female (68.5%) and Black (62.43%). The mean CES-D score was 19.7 ± 10.3, with 61.4% of participants at risk for depression. The depressive symptoms were significantly related to asthma control [β = −0.085, 95% confidence interval (CI) = −0.14 to −0.03] but not to prevention [relative risk (RR) = 1.00, 95% CI = 0.99–1.01], management (RR = 1.00, 95% CI = 0.99–1.01), or self-efficacy (β = −0.002, 95% CI = −0.01 to 0.01),ConclusionsIn this sample of rural adolescents, as depressive symptoms increased, asthma control declined. Depressive symptoms were not associated with asthma self-management, suggesting that the aspects of self-management we assessed are not an avenue by which depression impacts asthma control. Additional research is needed to further understand the relationship between depressive symptoms, asthma self-management, and control.
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- 2024
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21. β2-AR inhibition enhances EGFR antibody efficacy hampering the oxidative stress response machinery
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Del Vecchio, Vitale, Mele, Luigi, Panda, Sameer Kumar, Sanchez-Pajares, Ibone Rubio, Mosca, Laura, Tirino, Virginia, Barbieri, Massimiliano, Bruzzese, Francesca, Luciano, Antonio, Marino, Federica Zito, Accardo, Marina, Nicoletti, Giovanni Francesco, Papaccio, Gianpaolo, Barbieri, Antonio, and Desiderio, Vincenzo
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- 2023
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22. Anti-tumor necrosis factor α: originators versus biosimilars, comparison in clinical response assessment in a multicenter cohort of patients with inflammatory arthropathies
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C. Gioia, A. Picchianti Diamanti, R. Perricone, M.S. Chimenti, A. Afeltra, L. Navarini, A. Migliore, U. Massafra, V. Bruzzese, P. Scolieri, C. Meschini, M. Paroli, R. Caccavale, P. Scapato, R. Scrivo, F. Conti, B. Laganà, and M. Di Franco
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Biosimilars ,bioriginators ,anti-TNF ,inflammatory arthropathies ,Medicine ,Internal medicine ,RC31-1245 - Abstract
Objective. To compare etanercept and adalimumab biosimilars (SB4 and ABP501) and respective bioriginators in terms of safety and efficacy in a real-life contest. Methods. We consequently enrolled patients affected by rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, treated with SB4, and ABP501, or with corresponding originators, belonging to the main biological prescribing centers in the Lazio region (Italy), from 2017 to 2020. Data were collected at recruitment and after 4, 8, 12, and 24 months of therapy. Results. The multicenter cohort was composed by 455 patients treated with biosimilars [SB4/ABP501 276/179; female/male 307/146; biologic disease-modifying anti-rheumatic drug (b-DMARD) naïve 56%, median age/ interquartile range 55/46-65 years] and 436 treated with originators (etanercept/adalimumab 186/259, female/ male 279/157, b-DMARD naïve 67,2%, median age/interquartile range 53/43-62 years). No differences were found about safety, but the biosimilar group presented more discontinuations due to inefficacy (p
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- 2023
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23. 17O hyperfine spectroscopy in surface chemistry and catalysis
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Yu-Kai Liao, Paolo Cleto Bruzzese, Enrico Salvadori, and Mario Chiesa
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17O ,Hyperfine spectroscopy ,HYSCORE ,ENDOR ,Transition metal ions ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Physics ,QC1-999 - Abstract
Oxide-based materials are of key technological importance in different areas including advanced functional materials, solid state chemistry and catalysis. Many of the key questions concerning these areas involve understanding the chemical bond between the metal and the oxygen ions in the first or subsequent coordinating shells. The spectroscopic study of oxygen is therefore of fundamental importance to elucidate the complex interfacial coordination chemistry that underlies the development of metal-oxide supported catalysts and other advanced materials. Oxygen atoms at solid surfaces or lining the pores of zeolite frameworks play a vital role in stabilizing and defining the electronic and geometric structure of single metal atoms or clusters that act as catalytically active sites. In the case of paramagnetic species, EPR and its related hyperfine techniques offer a unique opportunity to explore and understand the nature of the chemical bonding in metal-oxide systems through the detection of the 17O hyperfine interaction. In this perspective we offer an overview of experimental considerations and relevant examples specific to 17O hyperfine spectroscopy of transition metal ions in zeolites relevant to catalysis. 17O hyperfine coupling values are obtained, which allow discriminating σ- and π-bonding channels in metal-oxygen bonds involving first-row transition metal ions. An exhaustive collection of 17O hyperfine and nuclear quadrupole couplings in different systems including molecular and biomolecular chemistry is provided, emphasizing the connection between interfacial and molecular inorganic coordination chemistry.
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- 2023
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24. ‘Our mind could be our biggest challenge’: A qualitative analysis of urban adolescents’ sleep experiences and opportunities for mind-body integrative health approaches to improve sleep
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Malia C. Maier, Jodi Y. Scharf, Melanie A. Gold, April J. Ancheta, Jean-Marie Bruzzese, and Samantha Garbers
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Sleep hygiene ,Mind-body integrative health ,Emotional freedom technique tapping ,Adolescent ,Focus groups ,Intervention development ,Public aspects of medicine ,RA1-1270 - Abstract
Objective: To inform the development of a combined sleep and mind-body integrative health (MBIH) intervention, we explored urban adolescents’ sleep experiences and perceptions of MBIH techniques. Methods: We conducted eight focus groups with school-based health center patients in New York City, exploring sleep experiences; mindfulness, body awareness, tapping, acupressure, and self-hypnosis; and intervention delivery preferences. We recorded, transcribed, and analyzed the discussions applying methods from grounded theory. Results: Participants (n = 25) were ages 14–17, predominantly female (64%), Latino (60%), and Black (40%). Participants reported social, physical, and internal sleep barriers, but had limited success implementing sleep improvement strategies. Participants viewed MBIH techniques positively, noted audio-guided techniques’ accessibility, and were intrigued by less-familiar techniques. Preferences varied around domains of intervention delivery. Conclusion: Results underscore the need for adolescent-informed interventions offering sleep improvement strategies. Participants’ interest and willingness to engage in MBIH techniques present an opportunity for practitioners to develop and deliver sleep interventions incorporating MBIH components to urban adolescents. Varied intervention preferences highlight the need to be adaptable to adolescents’ lived experiences, comfort levels, and learning styles. Innovation: This study elucidates the perspectives of underrepresented adolescents whose perspectives on MBIH have rarely been explored, an important first step in developing tailored interventions.
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- 2023
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25. An Analisys of Application Logs with Splunk : developing an App for the synthetic analysis of data and security incidents
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Bruzzese, Roberto
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Computer Science - Cryptography and Security ,Computer Science - Machine Learning - Abstract
The present work aims to enhance the application logs of an hypothetical infrastructure platform, and to build an App that displays the synthetic data about performance, anomalies and security incidents synthesized in the form of a Dashboard. The reference architecture, with multiple applications and multiple HW distribution, implementing a Service Oriented Architecture, is a real case of which the details have been abstracted because we want to extend the concept to all architectures with similar characteristics., Comment: 32 pages, 32 figures
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- 2019
26. The Initial Mass Function in the Extended Ultraviolet Disk of M83
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Bruzzese, Sarah M., Thilker, David A., Meurer, Gerhardt, Bianchi, Luciana, Watts, Adam B., Ferguson, Annette M. N., de Paz, Armando Gil, Madore, Barry F., Martin, D. Christopher, and Rich, R. Michael
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Astrophysics - Astrophysics of Galaxies - Abstract
Using Hubble Space Telescope ACS/WFC data we present the photometry and spatial distribution of resolved stellar populations of four fields within the extended ultraviolet disk (XUV disk) of M83. These observations show a clumpy distribution of main-sequence stars and a mostly smooth distribution of red giant branch stars. We constrain the upper-end of the initial mass function (IMF) in the outer disk using the detected population of main-sequence stars and an assumed constant star formation rate (SFR) over the last 300 Myr. By comparing the observed main-sequence luminosity function to simulations, we determine the best-fitting IMF to have a power law slope $\alpha=-2.35 \pm 0.3$ and an upper-mass limit $\rm M_{u}=25_{-3}^{+17} \, M_\odot$. This IMF is consistent with the observed H$\alpha$ emission, which we use to provide additional constraints on the IMF. We explore the influence of deviations from the constant SFR assumption, finding that our IMF conclusions are robust against all but strong recent variations in SFR, but these are excluded by causality arguments. These results, along with our similar studies of other nearby galaxies, indicate that some XUV disks are deficient in high-mass stars compared to a Kroupa IMF. There are over one hundred galaxies within 5 Mpc, many already observed with HST, thus allowing a more comprehensive investigation of the IMF, and how it varies, using the techniques developed here., Comment: MNRAS accepted. 28 pages, 7 Tables, 19 Figures. See published article or contact third author for paper with figures at full resolution. (V2: small error in metadata corrected)
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- 2019
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27. 17O hyperfine spectroscopy in surface chemistry and catalysis
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Liao, Yu-Kai, Bruzzese, Paolo Cleto, Salvadori, Enrico, and Chiesa, Mario
- Published
- 2023
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28. ‘Our mind could be our biggest challenge’: A qualitative analysis of urban adolescents’ sleep experiences and opportunities for mind-body integrative health approaches to improve sleep
- Author
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Maier, Malia C., Scharf, Jodi Y., Gold, Melanie A., Ancheta, April J., Bruzzese, Jean-Marie, and Garbers, Samantha
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- 2023
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29. Spontaneous cancer remission after COVID-19: insights from the pandemic and their relevance for cancer treatment
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Concetta Meo, Giuseppe Palma, Francesca Bruzzese, Alfredo Budillon, Claudio Napoli, and Filomena de Nigris
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Medicine - Abstract
Abstract Early in the COVID-19 pandemic, it emerged that the risk of severe outcomes was greater in patients with co-morbidities, including cancer. The huge effort undertaken to fight the pandemic, affects the management of cancer care, influencing their outcome. Despite the high fatality rate of COVID-19 disease in cancer patients, rare cases of temporary or prolonged clinical remission from cancers after SARS-CoV-2 infection have been reported. We have reviewed sixteen case reports of COVID-19 disease with spontaneous cancer reduction of progression. Fourteen cases of remission following viral infections and two after anti-SARS-CoV-2 vaccination. The immune response to COVID-19, may be implicated in both tumor regression, and progression. Specifically, we discuss potential mechanisms which include oncolytic and priming hypotheses, that may have contributed to the cancer regression in these cases and could be useful for future options in cancer treatment.
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- 2023
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30. Willingness to pay for certified wooden products: a critical literature review
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Poratelli Francesca, Blanc Simone, Pippinato Liam, Zanchini Raffaele, Bruzzese Stefano, and Brun Filippo
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voluntary certifications ,forest certifications ,wtp ,consumer ,critical review ,Forestry ,SD1-669.5 - Abstract
Forest certifications aim to promote sustainable forest management through the certification of forest products derived from forests managed according to a set of guidelines. However, managing a forest following the sustainability benchmarks indicated by the different certification systems has a higher cost than non-certified forests. This cost difference is therefore reflected in products made from these certified forests. An Environmentally Certified Timber Product (ECTP), in fact, should be more expensive than its identical competitor made from non-certified wood because of its higher management and chain of custody costs. The purpose of this review is to highlight how, over the past decade (2010–2020), customer willingness to pay (WTP) for ECTPs has been estimated and what parameters lead consumers to choose ECTPs. Results revealed several methodologies for estimating WTP, the main one being Contingent Valuation, although Discrete Choice Experiments would seem to be more effective. In monetary terms, the average WTP obtained ranges from 17% for products with a higher base price, such as furniture, up to 68% for those with a lower price, such as paper. Finally, several parameters drive consumers to choose ECTPs, such as socio-demographic factors, prior knowledge of brands and labels, and choice of product attributes.
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- 2023
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31. Dalbavancin for Acute Bacterial Skin and Skin Structure Infections in Pediatrics: Insights from Continuation Therapy Experience
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Sara Maria Scarano, Eugenia Bruzzese, Marco Poeta, Margherita Del Bene, Alfredo Guarino, and Andrea Lo Vecchio
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dalbavancin ,bacterial infection ,skin infection ,soft tissue infection ,ABSSSI ,children ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Acute Bacterial Skin and Skin Structure Infections (ABSSSI) are marked by substantial morbidity, frequent need for hospitalization, and long courses of intravenous antibiotic therapy. Herein, we report four cases of pediatric patients admitted for ABSSSI and managed with a combination antibiotic regimen incorporating dalbavancin: a second-generation lipoglycopeptide active against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. In our experience, particularly in a setting with a high methicillin-resistance rate, dalbavancin demonstrated safety and efficacy, simplifying ABSSSI management in childhood. Its prolonged half-life enables a single-dose administration regimen, offering potential solutions to numerous challenges encountered in pediatric care, such as extended hospital stays, difficulties in securing and maintaining vascular access, lack of pediatric-specific drug indications, and limited availability of suitable oral formulations.
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- 2024
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32. Osteonecrosis Múltiple inducida por glucocorticoides
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Juan Pablo Bruzzese Pérez, Gonzalo Harretche, Daniel Porcelli, and Claudio Rodriguez
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osteonecrosis ,osteonecrosis multiple ,glucocorticoides ,paciente jóven ,artroplastia ,Medicine ,Medicine (General) ,R5-920 - Abstract
La osteonecrosis múltiple es una entidad poco frecuente que se define por el compromiso de al menos tres regiones diferentes. Es indispensable el abordaje multidisciplinario de los pacientes que la padecen tanto para el diagnóstico como el tratamiento oportuno. Presentamos el caso clínico de un paciente joven que presenta una osteonecrosis múltiple con compromiso de ambas caderas, hombros, rodillas, codo derecho y cuello de pie izquierdo. El principal factor de riesgo presente en nuestro caso es el consumo de glucocorticoides.
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- 2023
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33. Efficacy of a gluten-free diet in reducing the widespread pain index and symptom severity scale in patients affected by fibromyalgia
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V. Bruzzese, C. Marrese, P. Scolieri, and J. Pepe
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Fibromyalgia ,celiac disease ,gluten-free diet ,widespread pain index ,symptom severity score ,Medicine ,Internal medicine ,RC31-1245 - Abstract
Objective. Dietary interventions to improve fibromyalgia (FM) symptoms reported conflicting results. This study aimed to treat FM patients with a gluten-free diet (GFD), alternated with a non-restricted gluten-containing diet, followed by a rechallenge of the GFD. Methods. Twenty postmenopausal women with FM and no history of celiac disease participated. A GFD was assigned for 6 months. This was followed by 3 months of a non-restricted gluten-containing diet and then a new GFD for another 6 months. At each visit, the widespread pain index (WPI) and the symptom severity scale (SS) scores were evaluated. Results. The mean age of the patients enrolled was 53.9±10 years. None of the patients had a diagnosis of irritable bowel disease, although they reported vague gastrointestinal symptoms. After 6 months of a GFD, a statistically significant reduction was observed for the WPI (10.3±1.8 vs 7.7±1.4; p
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- 2023
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34. P1644: ADP-DEPENDENT PLATELET ACTIVATION IS IMPORTANT IN THE DEVELOPMENT OF VENOUS THROMBOSIS DURING A LONG-DISTANCE FLIGHT
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Julie Tourn, Estelle Carminita, Lydie Crescence, Laurie Bruzzese, Nabil Adjriou, Regis Guieu, Christophe Dubois, and Laurence Panicot-Dubois
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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35. D'Accento
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Bruzzese, Angelo
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This music score was submitted for the Kaleidoscope 2020 Call for Scores ,an open access collaboration with the UCLA Music Library. - Published
- 2020
36. Varie Azioni
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Bruzzese, Angelo
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This music score was submitted for the Kaleidoscope 2020 Call for Scores ,an open access collaboration with the UCLA Music Library. - Published
- 2020
37. Couplet
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Bruzzese, Angelo
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This music score was submitted for the Kaleidoscope 2020 Call for Scores ,an open access collaboration with the UCLA Music Library. - Published
- 2020
38. Booster dose of SARS-CoV-2 messenger RNA vaccines strengthens the specific immune response of patients with rheumatoid arthritis: A prospective multicenter longitudinal study
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Chiara Farroni, Alessandra Aiello, Andrea Picchianti-Diamanti, Bruno Laganà, Elisa Petruccioli, Chiara Agrati, Anna Rosa Garbuglia, Silvia Meschi, Daniele Lapa, Gilda Cuzzi, Linda Petrone, Valentina Vanini, Andrea Salmi, Anna Maria Gerarda Altera, Federica Repele, Germana Grassi, Aurora Bettini, Serena Vita, Andrea Mariano, Arianna Damiani, Maria Infantino, Valentina Grossi, Mariangela Manfredi, Laura Niccoli, Vincenzo Puro, Roberta Di Rosa, Simonetta Salemi, Giorgio Sesti, Palma Scolieri, Vincenzo Bruzzese, Maurizio Benucci, Fabrizio Cantini, Emanuele Nicastri, and Delia Goletti
- Subjects
COVID-19 vaccine ,SARS-CoV-2 ,Rheumatoid arthritis ,T-cell response ,Antibody response ,Immunosuppressive therapy ,Infectious and parasitic diseases ,RC109-216 - Abstract
Objectives: To characterize the kinetics of humoral and T-cell responses in rheumatoid arthritis (RA)-patients followed up to 4-6 weeks (T3) after the SARS-CoV-2 vaccine booster dose. Methods: Health care workers (HCWs, n = 38) and patients with RA (n = 52) completing the messenger RNA vaccination schedule were enrolled at T3. In each cohort, 25 subjects were sampled after 5 weeks (T1) and 6 months (T2) from the first vaccine dose. The humoral response was assessed by measuring anti-receptor-binding domain (RBD) and neutralizing antibodies, the T-cell response by interferon-γ-release assay (IGRA), T cell cytokine production, and B cell phenotype at T3 by flow cytometry. Results: Patients with RA showed a significant reduction of antibody titers from T1 to T2 and a significant increase at T3. T-cell response by IGRA persisted over time in patients with RA, whereas it increased in HCWs. Most patients with RA scored positive for anti-RBD, neutralizing antibody and T-cell responses, although the magnitude was lower than HCWs. The spike-specific-cytokine response was mainly clusters of differentiation (CD)4+ T cells restricted in both cohorts and significantly lower with reduced interleukin-2 response and CD4-antigen-responding naïve T cells in patients with RA. Unswitched memory B cells were reduced in patients with RA compared with HCWs independently of vaccination. Conclusion: COVID-19 vaccine booster strengthens the humoral immunity in patients with RA even with a reduced cytokine response.
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- 2022
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39. High levels of blood circulating immune checkpoint molecules in children with new-onset type 1 diabetes are associated with the risk of developing an additional autoimmune disease
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Bruzzaniti, Sara, Piemonte, Erica, Mozzillo, Enza, Bruzzese, Dario, Lepore, Maria Teresa, Carbone, Fortunata, de Candia, Paola, Strollo, Rocky, Porcellini, Antonio, Marigliano, Marco, Maffeis, Claudio, Bifulco, Maurizio, Ludvigsson, Johnny, Franzese, Adriana, Matarese, Giuseppe, and Galgani, Mario
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- 2022
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40. Anxiety among pediatric asthma patients and their parents and quick-reliever medication use: The role of physical activity parenting behaviours
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Rogulj, Marijana, Vukojevic, Katarina, Bruzzese, Jean-Marie, and Lusic Kalcina, Linda
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- 2023
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41. Accuracy of QuantiFERON SARS-CoV-2 research use only assay and characterization of the CD4+ and CD8+ T cell-SARS-CoV-2 response: comparison with a homemade interferon-γ release assay
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Alessandra Aiello, Andrea Coppola, Valentina Vanini, Linda Petrone, Gilda Cuzzi, Andrea Salmi, Anna Maria Gerarda Altera, Carla Tortorella, Gina Gualano, Claudio Gasperini, Palma Scolieri, Alessia Beccacece, Serena Vita, Vincenzo Bruzzese, Roberto Lorenzetti, Fabrizio Palmieri, Emanuele Nicastri, and Delia Goletti
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QuantiFERON SARS-CoV-2 tubes ,Whole-blood ,Spike peptides ,IFN-γ release assay (IGRA), T cell response ,COVID-19 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Objectives: In this study, we aimed to characterize the SARS-CoV-2-specific T cell response detected by the QuantiFERON SARS-CoV-2 research use only assay in terms of accuracy and T cell subsets involved compared with a homemade interferon (IFN)-γ release assay (IGRA).Methods: We evaluated T cell response by the standardized QuantiFERON SARS-CoV-2 tubes (antigen [Ag]1 and Ag2) and a homemade IGRA quantifying IFN-γ response to SARS-CoV-2 spike peptides (homemade-IGRA-SPIKE test). We evaluated the T cell subsets mediating the specific response using flow cytometry.Results: We prospectively enrolled 66 individuals: COVID-19 or post-COVID-19 subjects and NO-COVID-19-vaccinated subjects, including healthy donors and immunocompromised subjects. The standardized kit detected 62.1% (41/66) of T cell responders. Ag2 tube showed a higher IFN-γ quantitative and qualitative response. Ag1 tube response was mainly mediated by CD4+ T cells; Ag2 tube response was mediated by CD4+ and CD8+ T cells. The homemade-IGRA-SPIKE test detected a higher number of responders (52/66, 78.8%) than the QuantiFERON SARS-CoV-2 assay (P = 0.056). The response was found in both T cell subsets, although a higher magnitude and response rate was observed in the CD4+ T cell subset.Conclusion: The QuantiFERON SARS-CoV-2 response is mediated by CD4+ and CD8+ T cells. A lower number of responders is found compared with the homemade-IGRA-SPIKE test, likely because of the different peptide composition.
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- 2022
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42. Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: a multicenter, retrospective, real-world experience with 200 cases outside of controlled clinical trials
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Massimo Gentile, Ernesto Vigna, Salvatore Palmieri, Monica Galli, Daniele Derudas, Roberto Mina, Roberta Della Pepa, Renato Zambello, Enrica Antonia Martino, Antonella Bruzzese, Silvia Mangiacavalli, Elena Zamagni, Catello Califano, Maurizio Musso, Concetta Conticello, Claudio Cerchione, Giuseppe Mele, Nicola Di Renzo, Massimo Offidani, Giuseppe Tarantini, Gloria Margiotta Casaluci, Angela Rago, Roberto Ria, Giuseppina Uccello, Gregorio Barilà, Gaetano Palumbo, Alessandra Pompa, Donatella Vincelli, Marino Brunori, Fabrizio Accardi, Valeria Amico, Angela Amendola, Raffaele Fontana, Velia Bongarzoni, Bernardo Rossini, Emilia Cotzia, Alessandro Gozzetti, Rita Rizzi, Nicola Sgherza, Eleonora Ferretti, Giuseppe Bertuglia, Davide Nappi, Maria Teresa Petrucci, Francesco Di Raimondo, Antonino Neri, Fortunato Morabito, and Pellegrino Musto
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
In the ELOQUENT-3 trial, the combination of elotuzumab, pomalidomide and dexamethasone (EloPd) proved to have a superior clinical benefit over pomalidomide and dexamethasone with a manageable toxicity profile, leading to its approval for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. We report here a real-world experience of 200 cases of RRMM treated with EloPd in 35 Italian centers outside of clinical trials. In our dataset, the median number of prior lines of therapy was two, with 51% of cases undergoing autologous stem cell transplant and 73% having been exposed to daratumumab. After a median follow-up of 9 months, 126 patients had stopped EloPd, most of them (88.9%) because of disease progression. The overall response rate was 55.4%, a finding in line with the pivotal trial results. Regarding adverse events, the toxicity profile in our cohort was similar to that in the ELOQUENT-3 trial, with no significant differences between younger (
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- 2023
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43. Pertussis outbreak in neonates and young infants across Italy, January to May 2024: implications for vaccination strategies
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Poeta, Marco, primary, Moracas, Cristina, additional, Albano, Chiara, additional, Petrarca, Laura, additional, Maglione, Marco, additional, Pierri, Luca, additional, Carta, Maurizio, additional, Montaldo, Paolo, additional, Venturini, Elisabetta, additional, De Luca, Maia, additional, Buonsenso, Danilo, additional, Brambilla, Ilaria, additional, Giacomet, Vania, additional, Lo Vecchio, Andrea, additional, Bruzzese, Eugenia, additional, Midulla, Fabio, additional, Colomba, Claudia, additional, and Guarino, Alfredo, additional
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- 2024
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44. Exploring the Quality of Narrative Feedback Provided to Residents During Ambulatory Patient Care in Medicine and Surgery
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Rebecca Leclair, Jessica S. S. Ho, Heather Braund, Ekaterina Kouzmina, Samantha Bruzzese, Sara Awad, Steve Mann, and Boris Zevin
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Special aspects of education ,LC8-6691 ,Medicine (General) ,R5-920 - Abstract
OBJECTIVES The transition to competency-based medical education (CBME) has increased the volume of residents’ assessment data; however, the quality of the narrative feedback is yet to be used as feedback-on-feedback for faculty. Our objectives were (1) to explore and compare the quality and content of narrative feedback provided to residents in medicine and surgery during ambulatory patient care and (2) to use the Deliberately Developmental Organization framework to identify strengths, weaknesses, and opportunities to improve quality of feedback within CBME. METHODS We conducted a mixed convergent methods study with residents from the Departments of Surgery (DoS; n = 7) and Medicine (DoM; n = 9) at Queen's University. We used thematic analysis and the Quality of Assessment for Learning (QuAL) tool to analyze the content and quality of narrative feedback documented in entrustable professional activities (EPAs) assessments for ambulatory care. We also examined the association between the basis of assessment, time to provide feedback, and the quality of narrative feedback. RESULTS Forty-one EPA assessments were included in the analysis. Three major themes arose from thematic analysis: Communication, Diagnostics/Management, and Next Steps. Quality of the narrative feedback varied; 46% had sufficient evidence about residents’ performance; 39% provided a suggestion for improvement; and 11% provided a connection between the suggestion and the evidence. There were significant differences between DoM and DoS in quality of feedback scores for evidence (2.1 [1.3] vs. 1.3 [1.1]; p
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- 2023
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45. Isolated Valve Amyloid Deposition in Aortic Stenosis: Potential Clinical and Pathophysiological Relevance
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Maddalena Conte, Paolo Poggio, Maria Monti, Laura Petraglia, Serena Cabaro, Dario Bruzzese, Giuseppe Comentale, Aurelio Caruso, Mariagabriella Grimaldi, Emilia Zampella, Annarita Gencarelli, Maria Rosaria Cervasio, Flora Cozzolino, Vittoria Monaco, Veronika Myasoedova, Vincenza Valerio, Adele Ferro, Luigi Insabato, Michele Bellino, Gennaro Galasso, Francesca Graziani, Pietro Pucci, Pietro Formisano, Emanuele Pilato, Alberto Cuocolo, Pasquale Perrone Filardi, Dario Leosco, and Valentina Parisi
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aortic stenosis ,amyloidosis ,inflammation ,aortic valve interstitial cells ,serum amyloid A ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Amyloid deposition within stenotic aortic valves (AVs) also appears frequent in the absence of cardiac amyloidosis, but its clinical and pathophysiological relevance has not been investigated. We will elucidate the rate of isolated AV amyloid deposition and its potential clinical and pathophysiological significance in aortic stenosis (AS). In 130 patients without systemic and/or cardiac amyloidosis, we collected the explanted AVs during cardiac surgery: 57 patients with calcific AS and 73 patients with AV insufficiency (41 with AV sclerosis and 32 without, who were used as controls). Amyloid deposition was found in 21 AS valves (37%), 4 sclerotic AVs (10%), and none of the controls. Patients with and without isolated AV amyloid deposition had similar clinical and echocardiographic characteristics and survival rates. Isolated AV amyloid deposition was associated with higher degrees of AV fibrosis (p = 0.0082) and calcification (p < 0.0001). Immunohistochemistry analysis suggested serum amyloid A1 (SAA1), in addition to transthyretin (TTR), as the protein possibly involved in AV amyloid deposition. Circulating SAA1 levels were within the normal range in all groups, and no difference was observed in AS patients with and without AV amyloid deposition. In vitro, AV interstitial cells (VICs) were stimulated with interleukin (IL)-1β which induced increased SAA1-mRNA both in the control VICs (+6.4 ± 0.5, p = 0.02) and the AS VICs (+7.6 ± 0.5, p = 0.008). In conclusion, isolated AV amyloid deposition is frequent in the context of AS, but it does not appear to have potential clinical relevance. Conversely, amyloid deposition within AV leaflets, probably promoted by local inflammation, could play a role in AS pathophysiology.
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- 2024
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46. Post-Harvest Atmospheric Pressure and Composition Modify the Concentration and Bioaccessibility of α- and β-Carotene in Carrots and Sweet Potatoes
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Batoul Hamieh, Patrick Borel, Sana Raouche, Laurie Bruzzese, Nabil Adjriou, Charlotte Halimi, Gregory Marconot, Guillian Gillet, Jean-Claude Rostain, Régis Guieu, and Charles Desmarchelier
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carotenoids ,vitamin A ,bioavailability ,process ,food matrix ,Chemical technology ,TP1-1185 - Abstract
Provitamin A (proVA) carotenoid synthesis and degradation are strongly influenced by environmental factors, including during post-harvest storage. Hypobaric and hyperbaric storages increase the shelf-life of many crops, but their effects on proVA carotenoids are not known. Our aim was to investigate the effects of modifications of atmospheric pressure and composition on α- and β-carotene concentration and bioaccessibility during the post-harvest storage of carrots and sweet potatoes. Vegetables were stored for 11–14 days at 20 °C in the dark in chambers with modified pressure and O2 concentrations. In carrots, α- and β-carotene concentrations increased significantly during storage, but compared to the control, they were significantly lower in hyperbaria (−23 and −26%, respectively), whereas they did not differ significantly in hypoxia and hypobaria. In sweet potatoes, α- and β-carotene concentrations decreased significantly during storage, but neither hypoxia, hypobaria nor hyperbaria led to any significant change compared to the control. There was a significant increase for carrot α- and β-carotene bioaccessibility in hypobaria and hyperbaria, while there was a significant decrease for sweet potato β-carotene bioaccessibility in hypobaria/hypoxia and normobaria/hypoxia (−45% and −65% vs. control, respectively). Atmospheric pressure and composition during the post-harvest storage of carrots and sweet potatoes modified the concentration and bioaccessibility of proVA carotenoids.
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- 2023
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47. Star formation in the outskirts of DDO 154: A top-light IMF in a nearly dormant disc
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Watts, Adam B., Meurer, Gerhardt R., Lagos, Claudia D. P., Bruzzese, Sarah M., Kroupa, Pavel, and Jerabkova, Tereza
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Astrophysics - Astrophysics of Galaxies - Abstract
We present optical photometry of Hubble Space Telescope (HST) ACS/WFC data of the resolved stellar populations in the outer disc of the dwarf irregular galaxy DDO 154. The photometry reveals that young main sequence stars are almost absent from the outermost HI disc. Instead, most are clustered near the main stellar component of the galaxy. We constrain the stellar initial mass function (IMF) by comparing the luminosity function of the main sequence stars to simulated stellar populations assuming a constant star formation rate over the dynamical timescale. The best-fitting IMF is deficient in high mass stars compared to a canonical Kroupa IMF, with a best-fit slope $\alpha = -2.45$ and upper mass limit $M_U = 16\ M_{\odot}$. This top-light IMF is consistent with predictions of the Integrated Galaxy-wide IMF theory. Combining the HST images with HI data from The HI Nearby Galaxy Survey Treasury (THINGS) we determine the star formation law (SFL) in the outer disc. The fit has a power law exponent $N = 2.92 \pm0.22$ and zero point $A=4.47 \pm 0.65 \times 10^{-7} \ M_{\odot} \ \text{yr}^{-1} \ \text{kpc}^{-2}$. This is depressed compared to the Kennicutt-Schmidt Star Formation Law, but consistent with weak star formation observed in diffuse HI environments. Extrapolating the SFL over the outer disc implies that there could be significant star formation occurring that is not detectable in H$\alpha$. Last, we determine the Toomre stability parameter $Q$ of the outer disc of DDO 154 using the THINGS HI rotation curve and velocity dispersion map. 72% of the HI in our field has $Q\leq 4$ and this incorporates 96% of the observed MS stars. Hence 28% of the HI in the field is largely dormant., Comment: 14 pages, 15 figures, accepted for publication in MNRAS
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- 2018
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48. Booster dose of SARS-CoV-2 messenger RNA vaccines strengthens the specific immune response of patients with rheumatoid arthritis: A prospective multicenter longitudinal study
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Farroni, Chiara, Aiello, Alessandra, Picchianti-Diamanti, Andrea, Laganà, Bruno, Petruccioli, Elisa, Agrati, Chiara, Garbuglia, Anna Rosa, Meschi, Silvia, Lapa, Daniele, Cuzzi, Gilda, Petrone, Linda, Vanini, Valentina, Salmi, Andrea, Altera, Anna Maria Gerarda, Repele, Federica, Grassi, Germana, Bettini, Aurora, Vita, Serena, Mariano, Andrea, Damiani, Arianna, Infantino, Maria, Grossi, Valentina, Manfredi, Mariangela, Niccoli, Laura, Puro, Vincenzo, Rosa, Roberta Di, Salemi, Simonetta, Sesti, Giorgio, Scolieri, Palma, Bruzzese, Vincenzo, Benucci, Maurizio, Cantini, Fabrizio, Nicastri, Emanuele, and Goletti, Delia
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- 2022
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49. Inhibition of autophagy by chloroquine prevents resistance to PI3K/AKT inhibitors and potentiates their antitumor effect in combination with paclitaxel in triple negative breast cancer models
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Stefania Cocco, Alessandra Leone, Maria Serena Roca, Rita Lombardi, Michela Piezzo, Roberta Caputo, Chiara Ciardiello, Susan Costantini, Francesca Bruzzese, Maria José Sisalli, Alfredo Budillon, and Michelino De Laurentiis
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Breast Cancer ,TNBC ,Autophagy ,PI3K/AKT/mTOR inhibitors ,Chloroquine ,Medicine - Abstract
Abstract Background Triple negative breast cancer (TNBC) is an aggressive disease characterized by high risk of relapse and development of resistance to different chemotherapy agents. Several targeted therapies have been investigated in TNBC with modest results in clinical trials. Among these, PI3K/AKT inhibitors have been evaluated in addition to standard therapies, yielding conflicting results and making attempts on elucidating inherent mechanisms of resistance of great interest. Increasing evidences suggest that PI3K/AKT inhibitors can induce autophagy in different cancers. Autophagy represents a supposed mechanism of drug-resistance in aggressive tumors, like TNBC. We, therefore, investigated if two PI3K/AKT inhibitors, ipatasertib and taselisib, could induce autophagy in breast cancer models, and whether chloroquine (CQ), a well known autophagy inhibitor, could potentiate ipatasertib and taselisib anti-cancer effect in combination with conventional chemotherapy. Methods The induction of autophagy after ipatasertib and taselisib treatment was evaluated in MDAMB231, MDAM468, MCF7, SKBR3 and MDAB361 breast cancer cell lines by assaying LC3-I conversion to LC3-II through immunoblotting and immunofluorescence. Other autophagy-markers as p62/SQSTM1 and ATG5 were evaluated by immunoblotting. Synergistic antiproliferative effect of double and triple combinations of ipatasertib/taselisib plus CQ and/or paclitaxel were evaluated by SRB assay and clonogenic assay. Anti-apoptotic effect of double combination of ipatasertib/taselisib plus CQ was evaluated by increased cleaved-PARP by immunoblot and by Annexin V- flow cytometric analysis. In vivo experiments were performed on xenograft model of MDAMB231 in NOD/SCID mice. Results Our results suggested that ipatasertib and taselisib induce increased autophagy signaling in different breast cancer models. This effect was particularly evident in PI3K/AKT resistant TNBC cells, where the inhibition of autophagy by CQ potentiates the therapeutic effect of PI3K/AKT inhibitors in vitro and in vivo TNBC models, synergizing with taxane-based chemotherapy. Conclusion These data suggest that inhibition of authophagy with CQ could overcome mechanism of drug resistance to PI3K/AKT inhibitors plus paclitaxel in TNBC making the evaluation of such combinations in clinical trials warranted.
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- 2022
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50. Accuracy of QuantiFERON SARS-CoV-2 research use only assay and characterization of the CD4+ and CD8+ T cell-SARS-CoV-2 response: comparison with a homemade interferon-γ release assay
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Aiello, Alessandra, Coppola, Andrea, Vanini, Valentina, Petrone, Linda, Cuzzi, Gilda, Salmi, Andrea, Altera, Anna Maria Gerarda, Tortorella, Carla, Gualano, Gina, Gasperini, Claudio, Scolieri, Palma, Beccacece, Alessia, Vita, Serena, Bruzzese, Vincenzo, Lorenzetti, Roberto, Palmieri, Fabrizio, Nicastri, Emanuele, and Goletti, Delia
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- 2022
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