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2. Functional, pathogenic, and pharmacological roles of protein folding intermediates

Author

Biasini, E, Faccioli, P, Biasini E., Faccioli P., Biasini, E, Faccioli, P, Biasini E., and Faccioli P.

Abstract

Protein expression and function in eukaryotic cells are tightly harmonized processes modulated by the combination of different layers of regulation, including transcription, processing, stability, and translation of messenger RNA, as well as assembly, maturation, sorting, recycling, and degradation of polypeptides. Integrating all these pathways and the protein quality control machinery, deputed to avoid the production and accumulation of aberrantly folded proteins, determines protein homeostasis. Over the last decade, the combined development of accurate time-resolved experimental techniques and efficient computer simulations has opened the possibility of investigating biological mechanisms at atomic resolution with physics-based models. A meaningful example is the reconstruction of protein folding pathways at atomic resolution, which has enabled the characterization of the folding kinetics of biologically relevant globular proteins consisting of a few hundred amino acids. Combining these innovative computational technologies with rigorous experimental approaches reveals the existence of non-native metastable states transiently appearing along the folding process of such proteins. Here, we review the primary evidence indicating that these protein folding intermediates could play roles in disparate biological processes, from the posttranslational regulation of protein expression to disease-relevant protein misfolding mechanisms. Finally, we discuss how the information encoded into protein folding pathways could be exploited to design an entirely new generation of pharmacological agents capable of promoting the selective degradation of protein targets.

Published
2023

3. Outcomes of Sorafenib and Metronomic Capecitabine in Child-Pugh B patients with advanced hepatocellular carcinoma in the era of immunotherapy: A real-life comparison with best supportive care

Author

Stefanini, B., primary, Bucci, L., additional, Santi, V., additional, Reggidori, N., additional, Lani, L., additional, Granito, A., additional, Pellizzaro, F., additional, Cabibbo, G., additional, Di Marco, M., additional, Ghittoni, G., additional, Campani, C., additional, Svegliati-Baroni, G., additional, Foschi, F.G., additional, Giannini, E.G., additional, Biasini, E., additional, Saitta, C., additional, Magalotti, D., additional, Sangiovanni, A., additional, Morisco, F., additional, Gasbarrini, A., additional, Rapaccini, G.L., additional, Masotto, A., additional, Sacco, R., additional, Vidili, G., additional, Mega, A., additional, Azzaroli, F., additional, Nardone, G., additional, Brandi, G., additional, Sabbioni, S., additional, Brunetto, M.R., additional, Vitale, A., additional, and Trevisani, F., additional

Published
2023
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4. Lack of substantial improvements in the landscape of alcohol-related hepatocellular carcinoma in the last 15 years: The need to improve cancer prevention and surveillance

Author

Reggidori, N., primary, Bucci, L., additional, Santi, V., additional, Stefanini, B., additional, Lani, L., additional, Rampoldi, D., additional, Caturelli, E., additional, Farinati, F., additional, Masotto, A., additional, Mega, A., additional, Biasini, E., additional, Foschi, F.G., additional, Svegliati-Baroni, G., additional, Sangiovanni, A., additional, Campani, C., additional, Raimondo, G., additional, Vidili, G., additional, Gasbarrini, A., additional, Celsa, C., additional, Di Marco, M., additional, Giannini, E.G., additional, Sacco, R., additional, Brunetto, M.R., additional, Azzaroli, F., additional, Magalotti, D., additional, Morisco, F., additional, Rapaccini, G.L., additional, Nardone, G., additional, Vitale, A., additional, and Trevisani, F., additional

Published
2023
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5. Comparison of prognostic models in advanced hepatocellular carcinoma patients undergoing Sorafenib: A multicenter study

Author

Marasco, G, Colecchia, A, Bacchi Reggiani ML, Celsa, C, Farinati, F, Giannini, Eg, Benevento, F, Rapaccini, Gl, Caturelli, E, Di Marco, M, Biasini, E, Marra, F, Morisco, F, Foschi, Fg, Zoli, M, Gasbarrini, A, Baroni, Gs, Masotto, A, Sacco, R, Raimondo, G, Azzaroli, F, Mega, A, Vidili, G, Brunetto, Mr, Nardone, G, Dajti, E, Ravaioli, F, Avanzato, F, Festi, D, Trevisani, F, group, Italian Liver Cancer (ITA. LI. CA., Marasco G., Colecchia A., Bacchi Reggiani M.L., Celsa C., Farinati F., Giannini E.G., Benevento F., Rapaccini G.L., Caturelli E., Di Marco M., Biasini E., Marra F., Morisco F., Foschi F.G., Zoli M., Gasbarrini A., Baroni G.S., Masotto A., Sacco R., Raimondo G., Azzaroli F., Mega A., Vidili G., Brunetto M.R., Nardone G., Dajti E., Ravaioli F., Avanzato F., Festi D., Trevisani F., Marasco, G., Colecchia, A., Bacchi Reggiani, M. L., Celsa, C., Farinati, F., Giannini, E. G., Benevento, F., Rapaccini, G. L., Caturelli, E., Di Marco, M., Biasini, E., Marra, F., Morisco, F., Foschi, F. G., Zoli, M., Gasbarrini, A., Baroni, G. S., Masotto, A., Sacco, R., Raimondo, G., Azzaroli, F., Mega, A., Vidili, G., Brunetto, M. R., Nardone, G., Dajti, E., Ravaioli, F., Avanzato, F., Festi, D., and Trevisani, F.

Subjects
Oncology, Male, Survival, Hepatocellular carcinoma, Cohort study, Hepatocellular carcinoma, Prognosis, Sorafenib, Survival, Severity of Illness Index, Antineoplastic Agent, 0302 clinical medicine, Prospective Studies, Liver Neoplasms, Gastroenterology, Middle Aged, Sorafenib, Prognosis, Treatment Outcome, Italy, Liver Neoplasm, 030220 oncology & carcinogenesis, Cohort, 030211 gastroenterology & hepatology, Female, Liver cancer, Cohort study, medicine.drug, medicine.medical_specialty, Carcinoma, Hepatocellular, Prognosi, Settore MED/12 - GASTROENTEROLOGIA, Antineoplastic Agents, Risk Assessment, 03 medical and health sciences, Internal medicine, medicine, Humans, neoplasms, Prognostic models, Neoplasm Staging, Proportional Hazards Models, Retrospective Studies, Hepatology, business.industry, Settore MED/09 - MEDICINA INTERNA, Gold standard, medicine.disease, digestive system diseases, Multicenter study, business
Abstract

Background: Sorafenib is the gold standard therapy for the advanced hepatocellular carcinoma (HCC). No scoring/staging is universally accepted to predict the survival of these patients. Aims: To evaluate the accuracy of the available prognostic models for HCC to predict the survival of advanced HCC patients treated with Sorafenib included in the Italian Liver Cancer (ITA.LI.CA.) multicenter cohort. Methods: The performance of several prognostic scores was assessed through a Cox regression-model evaluating the C-index and the Akaike Information Criterion (AIC). Results: Data of 1129 patients were analyzed. The mean age of patients was 61.6 years, and 80.8% were male. During a median follow-up period of 13 months, 789 patients died. The median period of Sorafenib administration was 4 months. All the prognostic scores were able to predict the overall survival (p

Published
2021

6. Hepatectomy Versus Sorafenib in Advanced Non-Metastatic Hepatocellular Carcinoma: A Real-Life Multicentric Weighted Comparison

Author

Famularo, S, Donadon, M, Cipriani, F, Giuliante, F, Ferri, S, Celsa, C, Ferrero, A, Foschi, F, Baiocchi, G, Biasini, E, Campani, C, Valle, R, Pellizzaro, F, Baroni, G, Raimondo, G, Mega, A, Chiarelli, M, Maestri, M, Gasbarrini, A, Jovine, E, Grazi, G, Rapaccini, G, Ruzzenente, A, Morisco, F, Sacco, R, Memeo, R, Crespi, M, Antonucci, A, Bernasconi, D, Romano, F, Griseri, G, Aldrighetti, L, Torzilli, G, Trevisani, F, Famularo, Simone, Donadon, Matteo, Cipriani, Federica, Giuliante, Felice, Ferri, Silvia, Celsa, Ciro, Ferrero, Alessandro, Foschi, Francesco Giuseppe, Baiocchi, Gian Luca, Biasini, Elisabetta, Campani, Claudia, Valle, Raffaele Dalla, Pellizzaro, Filippo, Baroni, Gianluca Svegliati, Raimondo, Giovanni, Mega, Andrea, Chiarelli, Marco, Maestri, Marcello, Gasbarrini, Antonio, Jovine, Elio, Grazi, Gian Luca, Rapaccini, Gian Ludovico, Ruzzenente, Andrea, Morisco, Filomena, Sacco, Rodolfo, Memeo, Riccardo, Crespi, Michele, Antonucci, Adelmo, Bernasconi, Davide P, Romano, Fabrizio, Griseri, Guido, Aldrighetti, Luca, Torzilli, Guido, Trevisani, Franco, Famularo, S, Donadon, M, Cipriani, F, Giuliante, F, Ferri, S, Celsa, C, Ferrero, A, Foschi, F, Baiocchi, G, Biasini, E, Campani, C, Valle, R, Pellizzaro, F, Baroni, G, Raimondo, G, Mega, A, Chiarelli, M, Maestri, M, Gasbarrini, A, Jovine, E, Grazi, G, Rapaccini, G, Ruzzenente, A, Morisco, F, Sacco, R, Memeo, R, Crespi, M, Antonucci, A, Bernasconi, D, Romano, F, Griseri, G, Aldrighetti, L, Torzilli, G, Trevisani, F, Famularo, Simone, Donadon, Matteo, Cipriani, Federica, Giuliante, Felice, Ferri, Silvia, Celsa, Ciro, Ferrero, Alessandro, Foschi, Francesco Giuseppe, Baiocchi, Gian Luca, Biasini, Elisabetta, Campani, Claudia, Valle, Raffaele Dalla, Pellizzaro, Filippo, Baroni, Gianluca Svegliati, Raimondo, Giovanni, Mega, Andrea, Chiarelli, Marco, Maestri, Marcello, Gasbarrini, Antonio, Jovine, Elio, Grazi, Gian Luca, Rapaccini, Gian Ludovico, Ruzzenente, Andrea, Morisco, Filomena, Sacco, Rodolfo, Memeo, Riccardo, Crespi, Michele, Antonucci, Adelmo, Bernasconi, Davide P, Romano, Fabrizio, Griseri, Guido, Aldrighetti, Luca, Torzilli, Guido, and Trevisani, Franco

Abstract

OBJECTIVE: The aim of the study was to compare SURG vs SOR regarding the OS and progression-free survival (PFS) in a real-world clinical scenario. BACKGROUND DATA: The treatment for advanced nonmetastatic HCC belonging to the Barcelona Clinic Liver Cancer stage C (BCLC C) is still controversial. METHODS: BCLC C patients without extrahepatic spread and tumoral invasion of the main portal trunk were considered. Surgical patients were obtained from the HE.RC.O.LE.S. Register, whereas sorafenib patients were obtained from the ITA.LI.CA register The inverse probability weighting (IPW) method was adopted to balance the confounders between the 2 groups. RESULTS: Between 2008 and 2019, 478 patients were enrolled: 303 in SURG and 175 in SOR group. Eastern Cooperative Oncological Group Performance Status (ECOG-PS), presence of cirrhosis, steatosis, Child-Pugh grade, hepatitis B virus and hepatitis C virus, alcohol intake, collateral veins, bilobar disease, localization of the tumor thrombus, number of nodules, alpha-fetoprotein, age, and Charlson Comorbidity index were weighted by IPW to create two balanced pseudo-populations: SURG = 374 and SOR = 263. After IPW, 1-3-5 years OS was 83.6%, 68.1%, 55.9% for SURG, and 42.3%, 17.8%, 12.8% for SOR (P [removed]0, and by the intrahepatic location of portal vein invasion. At Cox regression, sorafenib treatment (hazard ratio 4.436; 95% confidence interval 3.19-6.15; P < 0.001) and Charlson Index (hazard ratio 1.162; 95% confidence interval 1.06-1.27; P = 0.010) were the only independent predictors of mortality. PFS at 1-3-5 years were 65.9%, 40.3%, 24.3% for SURG and 21.6%, 3.5%, 2.9% for SOR (P = 0.007). CONCLUSIONS: In BCLC C patients without extrahepatic spread but with intrahepatic portal invasion, liver resection, if feasible, was followed by better OS and PFS compared with sorafenib.

Published
2022

8. T.08.3 CHARACTERISTICS AND SURVIVAL OF PATIENTS WITH PRIMARY BILIARY CHOLANGITIS AND HEPATOCELLULAR CARCINOMA

Author

Giannini, E.G., primary, Pieri, G., additional, Labanca, S., additional, Plaz Torres, M.C., additional, Gasbarrini, A., additional, Biasini, E., additional, Campani, C., additional, Cazzagon, N., additional, Foschi, F.G., additional, Mega, A., additional, Masotto, A., additional, Raimondo, G., additional, Rapaccini, G.L., additional, Sacco, R., additional, Caturelli, E., additional, Guarino, M., additional, Tovoli, F., additional, Vidili, G., additional, Brunetto, M.R., additional, Nardone, G., additional, Svegliati-Baroni, G., additional, Magalotti, D., additional, Azzaroli, F., additional, Cabibbo, G., additional, Di Marco, M., additional, Sangiovanni, A., additional, and Trevisani, F., additional

Published
2022
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10. Full atomistic model of prion structure and conversion

Author

Spagnolli, G, Rigoli, M, Orioli, S, Sevillano, A, Faccioli, P, Wille, H, Biasini, E, Requena, J, Spagnolli G., Rigoli M., Orioli S., Sevillano A. M., Faccioli P., Wille H., Biasini E., Requena J. R., Spagnolli, G, Rigoli, M, Orioli, S, Sevillano, A, Faccioli, P, Wille, H, Biasini, E, Requena, J, Spagnolli G., Rigoli M., Orioli S., Sevillano A. M., Faccioli P., Wille H., Biasini E., and Requena J. R.

Published
2019

11. Ok google, how could i design therapeutics against prion diseases?

Author

Rigoli, M, Spagnolli, G, Faccioli, P, Requena, J, Biasini, E, Rigoli M., Spagnolli G., Faccioli P., Requena J. R., Biasini E., Rigoli, M, Spagnolli, G, Faccioli, P, Requena, J, Biasini, E, Rigoli M., Spagnolli G., Faccioli P., Requena J. R., and Biasini E.

Abstract

A number of previous successful attempts in the search for therapeutics for a variety of human pathologies highlight the importance of computational technologies in the drug discovery pipeline. This approach, often referred to as computer-aided drug design, is unfortunately inapplicable when the precise information regarding the three-dimensional structure of disease-associated proteins or the mechanism by which they are altered to generate misfolded isoforms are missing. A typical example is represented by prion diseases, fatal pathologies of the nervous system characterized by the conformational conversion of a physiological protein called PrP C into a misfolded and infectious isoform referred to as PrP Sc . Missing information regarding the atomic structure of PrP Sc as well as the mechanism of templated conversion of PrP C has severely halted the discovery of effective therapies for prion diseases. In this manuscript, we review emerging opportunities to apply computer-aided techniques to target PrP C , PrP Sc or to design inhibitors of prion replication, and discuss how these fast-evolving technologies could lay the groundwork for the application of entirely novel rational drug design schemes for these devastating pathologies.

Published
2019

12. Pharmacological inactivation of the prion protein by targeting a folding intermediate

Author

Spagnolli, G, Massignan, T, Astolfi, A, Biggi, S, Rigoli, M, Brunelli, P, Libergoli, M, Ianeselli, A, Orioli, S, Boldrini, A, Terruzzi, L, Bonaldo, V, Maietta, G, Lorenzo, N, Fernandez, L, Codeseira, Y, Tosatto, L, Linsenmeier, L, Vignoli, B, Petris, G, Gasparotto, D, Pennuto, M, Guella, G, Canossa, M, Altmeppen, H, Lolli, G, Biressi, S, Pastor, M, Requena, J, Mancini, I, Barreca, M, Faccioli, P, Biasini, E, Spagnolli, Giovanni, Massignan, Tania, Astolfi, Andrea, Biggi, Silvia, Rigoli, Marta, Brunelli, Paolo, Libergoli, Michela, Ianeselli, Alan, Orioli, Simone, Boldrini, Alberto, Terruzzi, Luca, Bonaldo, Valerio, Maietta, Giulia, Lorenzo, Nuria L, Fernandez, Leticia C, Codeseira, Yaiza B, Tosatto, Laura, Linsenmeier, Luise, Vignoli, Beatrice, Petris, Gianluca, Gasparotto, Dino, Pennuto, Maria, Guella, Graziano, Canossa, Marco, Altmeppen, Hermann C, Lolli, Graziano, Biressi, Stefano, Pastor, Manuel M, Requena, Jesús R, Mancini, Ines, Barreca, Maria L, Faccioli, Pietro, Biasini, Emiliano, Spagnolli, G, Massignan, T, Astolfi, A, Biggi, S, Rigoli, M, Brunelli, P, Libergoli, M, Ianeselli, A, Orioli, S, Boldrini, A, Terruzzi, L, Bonaldo, V, Maietta, G, Lorenzo, N, Fernandez, L, Codeseira, Y, Tosatto, L, Linsenmeier, L, Vignoli, B, Petris, G, Gasparotto, D, Pennuto, M, Guella, G, Canossa, M, Altmeppen, H, Lolli, G, Biressi, S, Pastor, M, Requena, J, Mancini, I, Barreca, M, Faccioli, P, Biasini, E, Spagnolli, Giovanni, Massignan, Tania, Astolfi, Andrea, Biggi, Silvia, Rigoli, Marta, Brunelli, Paolo, Libergoli, Michela, Ianeselli, Alan, Orioli, Simone, Boldrini, Alberto, Terruzzi, Luca, Bonaldo, Valerio, Maietta, Giulia, Lorenzo, Nuria L, Fernandez, Leticia C, Codeseira, Yaiza B, Tosatto, Laura, Linsenmeier, Luise, Vignoli, Beatrice, Petris, Gianluca, Gasparotto, Dino, Pennuto, Maria, Guella, Graziano, Canossa, Marco, Altmeppen, Hermann C, Lolli, Graziano, Biressi, Stefano, Pastor, Manuel M, Requena, Jesús R, Mancini, Ines, Barreca, Maria L, Faccioli, Pietro, and Biasini, Emiliano

Abstract

Recent computational advancements in the simulation of biochemical processes allow investigating the mechanisms involved in protein regulation with realistic physics-based models, at an atomistic level of resolution. These techniques allowed us to design a drug discovery approach, named Pharmacological Protein Inactivation by Folding Intermediate Targeting (PPI-FIT), based on the rationale of negatively regulating protein levels by targeting folding intermediates. Here, PPI-FIT was tested for the first time on the cellular prion protein (PrP), a cell surface glycoprotein playing a key role in fatal and transmissible neurodegenerative pathologies known as prion diseases. We predicted the all-atom structure of an intermediate appearing along the folding pathway of PrP and identified four different small molecule ligands for this conformer, all capable of selectively lowering the load of the protein by promoting its degradation. Our data support the notion that the level of target proteins could be modulated by acting on their folding pathways, implying a previously unappreciated role for folding intermediates in the biological regulation of protein expression.

Published
2021

13. The changing scenario of hepatocellular carcinoma in Italy: an update

Author

Garuti, F., Neri, A., Avanzato, F., Gramenzi, A., Rampoldi, D., Rucci, P., Farinati, F., Giannini, E. G., Piscaglia, F., Rapaccini, Gian Ludovico, Di Marco, Maria Teresa, Caturelli, E., Zoli, M., Sacco, R., Cabibbo, G., Marra, F., Mega, A., Morisco, F., Gasbarrini, Antonio, Svegliati-Baroni, G., Foschi, F. G., Missale, G., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Brunetto, M. R., Trevisani, F., Biselli, M., Caraceni, P., Santi, V., Granito, A., Muratori, L., Sansone, V., Tovoli, F., Dajti, E., Marasco, G., Ravaioli, F., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Cela, E. M., Facciorusso, A., Cacciato, V., Casagrande, E., Moscatelli, A., Pellegatta, G., De Matthaeis, Nicoletta, Allegrini, G., Lauria, V., Ghittoni, G., Pelecca, G., Chegai, F., Coratella, F., Ortenzi, M., Biasini, E., Olivani, A., Inno, A., Marchetti, F., Busacca, A., Camma, C., Di Martino, V., Rizzo, G. E. M., Franze, M. S., Saitta, C., Sauchella, A., Bevilacqua, V., Berardinelli, D., Borghi, A., Gardini, A. C., Conti, Francesco, Cucchetti, A., Dall'Aglio, A. C., Ercolani, G., Campani, C., Di Bonaventura, C., Gitto, S., Malerba, P. C. A., Capasso, Monica, Guarino, Mariateresa, Oliveri, F., Romagnoli, V., Rapaccini G. L. (ORCID:0000-0002-6467-857X), Di Marco M., Gasbarrini A. (ORCID:0000-0002-7278-4823), de Matthaeis N., Conti F., Capasso M., Guarino M., Garuti, F., Neri, A., Avanzato, F., Gramenzi, A., Rampoldi, D., Rucci, P., Farinati, F., Giannini, E. G., Piscaglia, F., Rapaccini, Gian Ludovico, Di Marco, Maria Teresa, Caturelli, E., Zoli, M., Sacco, R., Cabibbo, G., Marra, F., Mega, A., Morisco, F., Gasbarrini, Antonio, Svegliati-Baroni, G., Foschi, F. G., Missale, G., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Brunetto, M. R., Trevisani, F., Biselli, M., Caraceni, P., Santi, V., Granito, A., Muratori, L., Sansone, V., Tovoli, F., Dajti, E., Marasco, G., Ravaioli, F., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Cela, E. M., Facciorusso, A., Cacciato, V., Casagrande, E., Moscatelli, A., Pellegatta, G., De Matthaeis, Nicoletta, Allegrini, G., Lauria, V., Ghittoni, G., Pelecca, G., Chegai, F., Coratella, F., Ortenzi, M., Biasini, E., Olivani, A., Inno, A., Marchetti, F., Busacca, A., Camma, C., Di Martino, V., Rizzo, G. E. M., Franze, M. S., Saitta, C., Sauchella, A., Bevilacqua, V., Berardinelli, D., Borghi, A., Gardini, A. C., Conti, Francesco, Cucchetti, A., Dall'Aglio, A. C., Ercolani, G., Campani, C., Di Bonaventura, C., Gitto, S., Malerba, P. C. A., Capasso, Monica, Guarino, Mariateresa, Oliveri, F., Romagnoli, V., Rapaccini G. L. (ORCID:0000-0002-6467-857X), Di Marco M., Gasbarrini A. (ORCID:0000-0002-7278-4823), de Matthaeis N., Conti F., Capasso M., and Guarino M.

Abstract

Background and aims: Epidemiology of hepatocellular carcinoma (HCC) is changing in most areas of the world. This study aimed at updating the changing scenario of aetiology, clinical presentation, management and prognosis of HCC in Italy during the last 15 years. Methods: Retrospective analysis of the Italian Liver Cancer (ITA.LI.CA) database included 6034 HCC patients managed in 23 centres from 2004 to 2018. Patients were divided into three groups according to the date of cancer diagnosis (2004-2008, 2009-2013 and 2014-2018). Results: The main results were: (i) a progressive patient ageing; (ii) a progressive increase of non-viral cases and, particularly, of ‘metabolic’ and ‘metabolic + alcohol’ HCCs; (iii) a slightly decline of cases diagnosed under surveillance, but with an incremental use of the semiannual schedule; (iv) a favourable cancer stage migration; (v) an increased use of radiofrequency ablation to the detriment of percutaneous ethanol injection; (vi) improved outcomes of ablative and transarterial treatments; (vii) an improved overall survival (adjusted for the lead time in surveyed patients) in the last calendar period, particularly in viral patients; (viii) a large gap between the number of potential candidates (according to oncologic criteria and age) to liver transplant and that of transplanted patients. Conclusions: During the last 15 years several aspects of HCC scenario have changed, as well as its management. The improvement in patient survival observed in the last period was likely because of a larger use of thermal ablation with respect to the less effective alcohol injection and to an improved management of intermediate stage patients.

Published
2021

14. Identification of clinical phenotypes and related survival in patients with large hccs

Author

Carr, B. I., Guerra, V., Donghia, R., Farinati, F., Giannini, E. G., Muratori, L., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Sacco, R., Celsa, C., Campani, C., Mega, A., Guarino, M., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Biasini, E., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Brunetto, M. R., Trevisani, F., Rapaccini G. L. (ORCID:0000-0002-6467-857X), Di Marco M., Guarino M., Gasbarrini A. (ORCID:0000-0002-7278-4823), Carr, B. I., Guerra, V., Donghia, R., Farinati, F., Giannini, E. G., Muratori, L., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Sacco, R., Celsa, C., Campani, C., Mega, A., Guarino, M., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Biasini, E., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Brunetto, M. R., Trevisani, F., Rapaccini G. L. (ORCID:0000-0002-6467-857X), Di Marco M., Guarino M., and Gasbarrini A. (ORCID:0000-0002-7278-4823)

Abstract

Background. Hepatocellular carcinoma (HCC) factors, especially maximum tumor diameter (MTD), tumor multifocality, portal vein thrombosis (PVT), and serum alpha-fetoprotein (AFP), influence survival. Aim. To examine patterns of tumor factors in large HCC patients. Methods. A database of large HCC patients was examined. Results. A multiple Cox proportional hazard model on death identified low serum albumin levels and the presence of PVT and multifocality, with each having a hazard ratio ≥2.0. All combinations of these three parameters were examined in relation to survival. Using univariate Cox analysis, the combination of albumin >3.5 g/dL and the absence of both PVT and multifocality had the best survival rate, while all combinations that included the presence of PVT had poor survival and hazard ratios. We identified four clinical phenotypes, each with a distinct median survival: patients with or without PVT or multifocality plus serum albumin ≥3.5 (g/dL), with each subgroup displaying high (≥100 IU/mL) or low (<100 IU/mL) blood AFP levels. Across a range of MTDs, we identified only two significant trends, blood AFP and platelets. Conclusions. Patients with large HCCs have distinct phenotypes and survival, as identified by the combination of PVT, multifocality, and blood albumin levels.

Published
2021

15. Comparison of prognostic models in advanced hepatocellular carcinoma patients undergoing Sorafenib: A multicenter study

Author

Marasco, G., Colecchia, A., Bacchi Reggiani, M. L., Celsa, C., Farinati, F., Giannini, E. G., Benevento, F., Rapaccini, Gian Ludovico, Caturelli, E., Di Marco, Maria Teresa, Biasini, E., Marra, F., Morisco, F., Foschi, F. G., Zoli, M., Gasbarrini, Antonio, Baroni, G. S., Masotto, A., Sacco, R., Raimondo, G., Azzaroli, F., Mega, A., Vidili, G., Brunetto, M. R., Nardone, G., Dajti, E., Ravaioli, F., Avanzato, F., Festi, D., Trevisani, F., Rapaccini G. L. (ORCID:0000-0002-6467-857X), Di Marco M., Gasbarrini A. (ORCID:0000-0002-7278-4823), Marasco, G., Colecchia, A., Bacchi Reggiani, M. L., Celsa, C., Farinati, F., Giannini, E. G., Benevento, F., Rapaccini, Gian Ludovico, Caturelli, E., Di Marco, Maria Teresa, Biasini, E., Marra, F., Morisco, F., Foschi, F. G., Zoli, M., Gasbarrini, Antonio, Baroni, G. S., Masotto, A., Sacco, R., Raimondo, G., Azzaroli, F., Mega, A., Vidili, G., Brunetto, M. R., Nardone, G., Dajti, E., Ravaioli, F., Avanzato, F., Festi, D., Trevisani, F., Rapaccini G. L. (ORCID:0000-0002-6467-857X), Di Marco M., and Gasbarrini A. (ORCID:0000-0002-7278-4823)

Abstract

Background: Sorafenib is the gold standard therapy for the advanced hepatocellular carcinoma (HCC). No scoring/staging is universally accepted to predict the survival of these patients. Aims: To evaluate the accuracy of the available prognostic models for HCC to predict the survival of advanced HCC patients treated with Sorafenib included in the Italian Liver Cancer (ITA.LI.CA.) multicenter cohort. Methods: The performance of several prognostic scores was assessed through a Cox regression-model evaluating the C-index and the Akaike Information Criterion (AIC). Results: Data of 1129 patients were analyzed. The mean age of patients was 61.6 years, and 80.8% were male. During a median follow-up period of 13 months, 789 patients died. The median period of Sorafenib administration was 4 months. All the prognostic scores were able to predict the overall survival (p<0.001) at univariate analysis, except the Albumin-Bilirubin score. The Italian Liver Cancer score (CLIP) yielded the highest accuracy (C-index 0.604, AIC 9898), followed by the ITA.LI.CA. prognostic score (C-index 0.599, AIC 9915). Conclusions: The CLIP score had the highest accuracy in predicting the overall survival of HCC patients treated with Sorafenib, although its performance remained poor. Further studies are needed to refine the current ability to predict the outcome of HCC patients undergoing Sorafenib.

Published
2021

18. The cellular prion protein beyond prion diseases

Author

Manni, G, Lewis, V, Senesi, M, Spagnolli, G, Fallarino, F, Collins, SJ, Mouillet-Richard, S, Biasini, E, Manni, G, Lewis, V, Senesi, M, Spagnolli, G, Fallarino, F, Collins, SJ, Mouillet-Richard, S, and Biasini, E

Abstract

The cellular prion protein (PrPC), a cell surface glycoprotein originally identified for its central role in prion diseases (also called transmissible spongiform encephalopathies), has recently been implicated in the pathogenesis of other neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases, by acting as a toxicity-transducing receptor for different misfolded protein isoforms, or in some case by exerting neuroprotective effects. Interestingly, PrPC has also been reported to play unexpected functions outside the nervous system, for example by contributing to myelin homeostasis, regulating specific processes of the immune system and participating in various aspects of cancer progression. Collectively, these observations point to a much broader role for PrPC in physiological and disease processes than originally assumed. In this manuscript, we provide an overview of what is known about the role of PrPC beyond prion disorders and discuss the potential implications of targeting this protein in different diseases.

Published
2020

19. All-Atom Simulation of HET-s Prion Replication

Author

Terruzzi, L, Spagnolli, G, Boldrini, A, Requena, J, Biasini, E, Faccioli, P, Luca Terruzzi, Giovanni Spagnolli, Alberto Boldrini, Jesús R. Requena, Emiliano Biasini, Pietro Faccioli, Terruzzi, L, Spagnolli, G, Boldrini, A, Requena, J, Biasini, E, Faccioli, P, Luca Terruzzi, Giovanni Spagnolli, Alberto Boldrini, Jesús R. Requena, Emiliano Biasini, and Pietro Faccioli

Abstract

Prions are self-replicative protein particles lacking nucleic acids. Originally discovered for causing infectious neurodegenerative disorders, they have also been found to play several physiological roles in a variety of species. Functional and pathogenic prions share a common mechanism of replication, characterized by the ability of an amyloid conformer to propagate by inducing the conversion of its physiological, soluble counterpart. Since time-resolved biophysical experiments are currently unable to provide full reconstruction of the physico-chemical mechanisms responsible for prion replication, one must rely on computer simulations. In this work, we show that a recently developed algorithm called Self-Consistent Path Sampling (SCPS) overcomes the computational limitations of plain MD and provides a viable tool to investigate prion replication processes using state-of-the-art all-atom force fields in explicit solvent. First, we validate the reliability of SCPS simulations by characterizing the folding of a class of small proteins and comparing against the results of plain MD simulations. Next, we use SCPS to investigate the replication of the prion forming domain of HET-s, a physiological fungal prion for which high-resolution structural data are available. Our atomistic reconstruction shows remarkable similarities with a previously reported mechanism of mammalian PrPSc propagation obtained using a simpler and more approximate path sampling algorithm. Together, these results suggest that the propagation of prions generated by evolutionary distant proteins may share common features. In particular, in both these cases, prions propagate their conformation through a very similar templating mechanism.

Published
2020

20. Curative therapies are superior to standard of care (transarterial chemoembolization) for intermediate stage hepatocellular carcinoma

Author

Pecorelli A, Lenzi B, Gramenzi A, Garuti F, Farinati F, Giannini EG, Ciccarese F, Piscaglia F, Rapaccini GL, Di Marco M, Caturelli E, Zoli M, Borzio F, Sacco R, Cabibbo G, Felder M, Morisco F, Gasbarrini A, Baroni GS, Foschi FG, Biasini E, Masotto A, Virdone R, Bernardi M, Trevisani F, Bolondi L, Biselli M, Bucci L, Caraceni P, Cucchetti A, Domenicali M, Venerandi L, Giacomin A, Maddalo G, Pozzan C, Vani V, Poggio PD, Olmi S, Balsamo C, Vavassori E, Benvegnù L, Cappelli A, Golfieri R, Mosconi C, Renzulli M, Bosco G, Roselli P, Dell'Isola S, Ialungo AM, Bruzzone L, Picciotto A, Marenco S, Risso D, Sammito G, Savarino V, Cammà C, Maida M, Costantino A, Barcellona MR, Affronti A, Mega A, Rinninella E, Mismas V, Cappa FM, Dall'Aglio AC, Feletti V, Lanzi A, Neri E, Stefanini GF, Tamberi S, Missale G, Porro E, Guarino M, Gemini S, Schiadà L, for the Italian LiverCancer (ITA. LI. CA) group, Donatella Magalotti, Carla Serra, Pecorelli A, Lenzi B, Gramenzi A, Garuti F, Farinati F, Giannini EG, Ciccarese F, Piscaglia F, Rapaccini GL, Di Marco M, Caturelli E, Zoli M, Borzio F, Sacco R, Cabibbo G, Felder M, Morisco F, Gasbarrini A, Baroni GS, Foschi FG, Biasini E, Masotto A, Virdone R, Bernardi M, Trevisani F, Bolondi L, Biselli M, Bucci L, Caraceni P, Cucchetti A, Domenicali M, Magalotti D, Serra C, Venerandi L, Giacomin A, Maddalo G, Pozzan C, Vani V, Poggio PD, Olmi S, Balsamo C, Vavassori E, Benvegnù L, Cappelli A, Golfieri R, Mosconi C, Renzulli M, Bosco G, Roselli P, Dell'Isola S, Ialungo AM, Bruzzone L, Picciotto A, Marenco S, Risso D, Sammito G, Savarino V, Cammà C, Maida M, Costantino A, Barcellona MR, Affronti A, Mega A, Rinninella E, Mismas V, Cappa FM, Dall'Aglio AC, Feletti V, Lanzi A, Neri E, Stefanini GF, Tamberi S, Missale G, Porro E, Guarino M, Gemini S, Schiadà L, Pecorelli, A., Lenzi, B., Gramenzi, A., Garuti, F., Farinati, F., Giannini, E. G., Ciccarese, F., Piscaglia, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Cabibbo, G., Felder, M., Morisco, F., Gasbarrini, A., Baroni, G. S., Foschi, F. G., Biasini, E., Masotto, A., Virdone, R., Bernardi, M., Trevisani, F., Bolondi, L., Biselli, M., Bucci, L., Caraceni, P., Cucchetti, A., Domenicali, M., Magalotti, D., Serra, C., Venerandi, L., Giacomin, A., Maddalo, G., Pozzan, C., Vani, V., Poggio, P. D., Olmi, S., Balsamo, C., Vavassori, E., Benvegnu, L., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Bosco, G., Roselli, P., Dell'Isola, S., Ialungo, A. M., Bruzzone, L., Picciotto, A., Marenco, S., Risso, D., Sammito, G., Savarino, V., Camma, C., Maida, M., Costantino, A., Barcellona, M. R., Affronti, A., Mega, A., Rinninella, E., Mismas, V., Cappa, F. M., Dall'Aglio, A. C., Feletti, V., Lanzi, A., Neri, E., Stefanini, G. F., Tamberi, S., Missale, G., Porro, E., Guarino, M., Gemini, S., Schiada, L., Pecorelli, Anna, Lenzi, Barbara, Gramenzi, Annagiulia, Garuti, Francesca, Farinati, Fabio, Giannini, Edoardo G, Ciccarese, Francesca, Piscaglia, Fabio, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cabibbo, Giuseppe, Felder, Martina, Morisco, Filomena, Gasbarrini, Antonio, Baroni, Gianluca Svegliati, Foschi, Francesco G, Biasini, Elisabetta, Masotto, Alberto, Virdone, Roberto, Bernardi, Mauro, and Trevisani, Franco

Subjects
Sorafenib, Male, Niacinamide, medicine.medical_specialty, Standard of care, Carcinoma, Hepatocellular, Antineoplastic Agents, Gastroenterology, Intermediate stage, 03 medical and health sciences, 0302 clinical medicine, HCC, BCLC-B, Treatment, Hepatology, Internal medicine, medicine, Humans, Chemoembolization, Therapeutic, Propensity Score, Aged, Neoplasm Staging, Retrospective Studies, intermediate stage, treatment, business.industry, Patient Selection, Phenylurea Compounds, Liver Neoplasms, Settore MED/09 - MEDICINA INTERNA, Standard of Care, Middle Aged, medicine.disease, Survival Analysis, Treatment Outcome, Italy, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Propensity score matching, Multivariate Analysis, 030211 gastroenterology & hepatology, Female, Liver function, Liver cancer, business, medicine.drug
Abstract

Background and aims the Barcelona Clinic Liver Cancer intermediate stage (BCLC-B) of hepatocellular carcinoma (HCC) includes extremely heterogeneous patients in terms of tumor burden and liver function. Transarterial-chemoembolization (TACE) is the first-line treatment for these patients although it may be risky/useless for someone, while others could undergo curative treatments. This study assesses the treatment type performed in a large cohort of BCLC-B patients and its outcome. Methods retrospective analysis of 485 consecutive BCLC-B patients from the ITA.LI.CA database diagnosed with naive HCC after 1999. Patients were stratified by treatment. Results 29 patients (6%) were lost to follow-up before receiving treatment. Treatment distribution was: TACE (233, 51.1%), curative treatments (145 patients, 31.8%), sorafenib (18, 3.9%), other (39, 8.5%), best supportive care (BSC) (21, 4.6%). Median survival (95% CI) was 45 months (37.4-52.7) for curative treatments, 30 (24.7-35.3) for TACE, 14 (10.5-17.5) for sorafenib, 14 (5.2-22.7) for other treatments and 10 (6.0-14.2) for BSC (p

Published
2017

22. Laser ablation is superior to TACE in large-sized hepatocellular carcinoma: A pilot case-control study

Author

Morisco, Filomena, Camera, Silvia, Guarino, Maria, Tortora, Raffaella, Cossiga, Valentina, Vitiello, Anna, Cordone, Gabriella, Caporaso, Nicola, Di Costanzo, Giovan Giuseppe, Zoli, M., Garuti, F., Neri, A., Piscaglia, F., Lenzi, B., Valente, M., Trevisani, F., Bolondi, L., Biselli, M., Caraceni, P., Cucchetti, A., Domenicali, M., Gramenzi, A., Magalotti, D., Serra, C., Venerandi, L., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Giannini, E. G., Brunacci, M., Moscatelli, A., Pellegatta, G., Savarino, V., Caturelli, E., Roselli, P., Lauria, V., Pelecca, G., Dell'Isola, S., Ialungo, A. M., Rastrelli, E., Cabibbo, G., Cammà, C., Attardo, S., Rossi, M., Cavani, G., Virdone, R., Affronti, A., Nardone, G., Felder, M., Mega, A., Ciccarese, F., Del Poggio, P., Olmi, S., Foschi, F. G., Bevilacqua, V., Dall'Aglio, A. C., Ercolani, G., Fiorini, E., Casadei Gardini, A., Lanzi, A., Mirici Cappa, F., Sacco, R., Mismas, V., Svegliati Barone, G., Schiadà, L., Farinati, F., Gazzola, A., Murer, F., Pozzan, C., Vanin, V., Rapaccini, G. L., de Matthaeis, N., Gasbarrini, A., Rinninella, E., Olivani, A., Missale, G., Biasini, E., Di Marco, M., Balsamo, C., Vavassori, E., Masotto, A., Marchetti, F., Valerio, M., Marra, F., Aburas, S., Campani, C., Dragoni, G., Borzio, F., Benvegnù, L., Festi, D., Marasco, Giovanni, Ravaioli, Federico, Morisco, Filomena, Camera, Silvia, Guarino, Maria, Tortora, Raffaella, Cossiga, Valentina, Vitiello, Anna, Cordone, Gabriella, Caporaso, Nicola, Di Costanzo, Giovan Giuseppe, Zoli, M., Garuti, F., Neri, A., Piscaglia, F., Lenzi, B., Valente, M., Trevisani, F., Bolondi, L., Biselli, M., Caraceni, P., Cucchetti, A., Domenicali, M., Gramenzi, A., Magalotti, D., Serra, C., Venerandi, L., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Giannini, E.G., Brunacci, M., Moscatelli, A., Pellegatta, G., Savarino, V., Caturelli, E., Roselli, P., Lauria, V., Pelecca, G., Dell'Isola, S., Ialungo, A.M., Rastrelli, E., Cabibbo, G., Cammà, C., Attardo, S., Rossi, M., Cavani, G., Virdone, R., Affronti, A., Nardone, G., Felder, M., Mega, A., Ciccarese, F., Del Poggio, P., Olmi, S., Foschi, F.G., Bevilacqua, V., Dall'Aglio, A.C., Ercolani, G., Fiorini, E., Casadei Gardini, A., Lanzi, A., Mirici Cappa, F., Sacco, R., Mismas, V., Svegliati Barone, G., Schiadà, L., Farinati, F., Gazzola, A., Murer, F., Pozzan, C., Vanin, V., Rapaccini, G.L., de Matthaeis, N., Gasbarrini, A., Rinninella, E., Olivani, A., Missale, G., Biasini, E., Di Marco, M., Balsamo, C., Vavassori, E., Masotto, A., Marchetti, F., Valerio, M., Marra, F., Aburas, S., Campani, C., Dragoni, G., Borzio, F., Benvegnù, L., Festi, D., Marasco, Giovanni, Ravaioli, Federico, Giannini, E. G., Ialungo, A. M., Foschi, F. G., Dall'Aglio, A. C., Rapaccini, G. L., Garuti, Franca, Venerandi, Laura, Mega, Angela, Fiorini, Elisabetta, Lanzi, Andrea, and Balsamo, Carlo

Subjects
medicine.medical_specialty, Large HCC, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Survival rate, Laser ablation, TACE, Univariate analysis, business.industry, Standard treatment, Large HCC, Laser ablation, TACE, Oncology, Cancer, Hepatology, medicine.disease, BCLC Stage, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Liver cancer, business, Research Paper
Abstract

// Filomena Morisco 1 , Silvia Camera 1 , Maria Guarino 1 , Raffaella Tortora 2 , Valentina Cossiga 1 , Anna Vitiello 1 , Gabriella Cordone 2 , Nicola Caporaso 1 , Giovan Giuseppe Di Costanzo 2 and Italian Liver Cancer (ITA.LI.CA) group 1 Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Naples, Italy 2 Hepatology Unit, “Cardarelli” Hospital, Naples, Italy Correspondence to: Filomena Morisco, email: filomena.morisco@unina.it Keywords: large HCC; laser ablation; TACE Received: December 13, 2017 Accepted: February 27, 2018 Published: April 03, 2018 ABSTRACT Background: Limited therapies are available for large (≥40 mm) unresectable hepatocellular carcinoma (HCC). Currently, the standard treatment with transarterial chemoembolisation (TACE) is unsatisfactory with high recurrence rate and limited effect on survival. Laser Ablation (LA) has emerged as a relatively new technique characterized by high efficacy and good safety. This study is aimed to evaluate the efficacy of LA in comparison to TACE in patients with large HCC. Methods: Eighty-two patients with a single HCC nodule ≥40 mm (BCLC stage A or B) were enrolled in this case-control study. Forty-one patients were treated with LA and 41 patients were treated with TACE. Response to therapy was evaluated according to the mRECIST criteria. Survival was calculated with Kaplan-Meier from the time of cancer diagnosis to death with values censored at the date of the last follow-up. Results: Twenty-six (63.4%) and 8 (19.5%) patients had a complete response after LA and TACE, respectively ( p 60 mm. LA resulted superior to TACE especially in nodules ranging between 51 and 60 mm in diameter, with a complete response rate post-LA and post-TACE of 75% and 14.3%, respectively ( p = 0.0133). The 36 months cumulative survival rate in patients treated with LA and TACE was 55.4% and 48.8%, respectively. The disease recurrence rates after LA and TACE were 19.5% and 75.0%, respectively. Conclusions: LA is a more effective therapeutic option than TACE in patients with solitary large HCC.

Published
2018

23. Metabolic disorders across hepatocellular carcinoma in Italy

Author

Morisco, F., Guarino, M., Valvano, M. R., Auriemma, F., Farinati, F., Giannini, E. G., Ciccarese, F., Tovoli, F., Rapaccini, Gian Ludovico, Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Cabibbo, G., Felder, M., Benvengu, L., Gasbarrini, Antonio, Svegliati Baroni, G., Foschi, F. G., Biasini, E., Masotto, A., Virdone, R., Marra, F., Caporaso, N., Trevisani, F., Sessa, A., Marafatto, F., Peserico, G., Pozzan, C., Brunacci, M., Moscatelli, A., Pellegatta, G., Savarino, V., Del Poggio, P., Olmi, S., De Matthaeis, Nicoletta, Balsamo, C., Vavassori, E., Roselli, P., Lauria, V., Pelecca, G., Mismas, V., Rossi, M., Attardo, S., Cavani, G., Mega, A., Rinninella, Emanuele, Ortolani, A., Bevilacqua, V., Chiara Dall'Aglio, A., Ercolani, G., Fiorini, Carlo Ettore, Casadei Gardini, A., Lanzi, Alessio, Mirici Cappa, F., Missale, G., Porro, E., Marchetti, F., Valerio, M., Affronti, A., Orlando, E., Rosa Barcellona, M., Aburas, S., Dragoni, G., Campani, C., Biselli, M., Bucci, L., Caraceni, P., Cucchetti, A., Domenicali, M., Garuti, F., Gramenzi, A., Magalotti, D., Serra, C., Granito, A., Negrini, G., Napoli, L., Piscaglia, F., Morisco, F., Guarino, M., Valvano, M. R., Auriemma, F., Farinati, F., Giannini, E. G., Ciccarese, F., Tovoli, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Cabibbo, G., Felder, M., Benvengu, L., Gasbarrini, A., Svegliati Baroni, G., Foschi, F. G., Biasini, E., Masotto, A., Virdone, R., Marra, F., Caporaso, N., Trevisani, F., Sessa, A., Marafatto, F., Peserico, G., Pozzan, C., Brunacci, M., Moscatelli, A., Pellegatta, G., Savarino, V., Del Poggio, P., Olmi, S., de Matthaeis, N., Balsamo, C., Vavassori, E., Roselli, P., Lauria, V., Pelecca, G., Mismas, V., Rossi, M., Attardo, S., Cavani, G., Mega, A., Rinninella, E., Ortolani, A., Bevilacqua, V., Chiara Dall'Aglio, A., Ercolani, G., Fiorini, E., Casadei Gardini, A., Lanzi, A., Mirici Cappa, F., Missale, G., Porro, E., Marchetti, F., Valerio, M., Affronti, A., Orlando, E., Rosa Barcellona, M., Aburas, S., Dragoni, G., Campani, C., Biselli, M., Bucci, L., Caraceni, P., Cucchetti, A., Domenicali, M., Garuti, F., Gramenzi, A., Magalotti, D., Serra, C., Granito, A., Negrini, G., Napoli, L., Piscaglia, F., Morisco, Filomena, Guarino, Maria, Valvano, Maria R., Auriemma, Francesco, Farinati, Fabio, Giannini, Edoardo G., Ciccarese, Francesca, Tovoli, Francesco, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cabibbo, Giuseppe, Felder, Martina, Benvengù, Luisa, Gasbarrini, Antonio, Svegliati Baroni, Gianluca, Foschi, Francesco G., Biasini, Elisabetta, Masotto, Alberto, Virdone, Roberto, Marra, Fabio, Caporaso, Nicola, Trevisani, Franco, Sessa, Anna, Marafatto, Filippo, Peserico, Giulia, Pozzan, Caterina, Brunacci, Matteo, Moscatelli, Alessandro, Pellegatta, Gaia, Savarino, Vincenzo, Del Poggio, Paolo, Olmi, Stefano, de Matthaeis, Nicoletta, Balsamo, Claudia, Vavassori, Elena, Roselli, Paola, Lauria, Valentina, Pelecca, Giorgio, Mismas, Valeria, Rossi, Margherita, Attardo, Simona, Cavani, Giulia, Mega, Andrea, Rinninella, Emanuele, Ortolani, Alessio, Bevilacqua, Vittoria, Chiara Dall'Aglio, Anna, Ercolani, Giorgio, Fiorini, Erica, Casadei Gardini, Andrea, Lanzi, Arianna, Mirici Cappa, Federica, Missale, Gabriele, Porro, Emanuela, Marchetti, Fabiana, Valerio, Matteo, Affronti, Andrea, Orlando, Emanuele, Rosa Barcellona, Maria, Aburas, Sami, Dragoni, Gabriele, Campani, Claudia, Biselli, Maurizio, Bucci, Laura, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Garuti, Francesca, Gramenzi, Annagiulia, Magalotti, Donatella, Serra, Carla, Granito, Alessandro, Negrini, Giulia, Napoli, Lucia, Piscaglia, Fabio, Valvano, Maria R, Giannini, Edoardo G, and Foschi, Francesco G

Subjects
Oncology, Male, obesity, Databases, Factual, Hepatocellular carcinoma, 0302 clinical medicine, Risk Factors, Prospective cohort study, diabetes, Metabolic disorder, Liver Neoplasms, Diabetes, hepatocellular carcinoma, Middle Aged, Metabolic syndrome, Portal vein thrombosis, Italy, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, medicine.medical_specialty, Carcinoma, Hepatocellular, Settore MED/12 - GASTROENTEROLOGIA, Obesity, metabolic syndrome, 03 medical and health sciences, Databases, Metabolic Diseases, Internal medicine, medicine, Diabetes Mellitus, Humans, Factual, Aged, Neoplasm Staging, Retrospective Studies, Hepatology, business.industry, Carcinoma, Hepatocellular, medicine.disease, Survival Analysis, BCLC Stage, Multivariate Analysis, diabete, Liver function, business
Abstract

Background: Metabolic disorders are well-known risk factors for HCC. Conversely, their impact on the natural history of HCC is not established. This study aimed at evaluating the impact of metabolic disorders on clinical features, treatment and survival of HCC patients regardless of its aetiology. Methods: We analysed the ITA.LI.CA database regarding 839 HCC patients prospectively collected. The following metabolic features were analysed: BMI, diabetes, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. According to these features, patients were divided into 3 groups: 0-1, 2 and 3-5 metabolic features. Results: As compared with patients with 0-1 metabolic features, patients with 3-5 features showed lower percentage of HCC diagnosis on surveillance (P=.021), larger tumours (P=.038), better liver function (higher percentage of Child-Pugh class A [P=.007] and MELD&nbsp

Published
2018

25. Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study

Author

Piscaglia, Fabio, Svegliati Baroni, Gianluca, Barchetti, Andrea, Pecorelli, Anna, Marinelli, Sara, Tiribelli, Claudio, Bellentani, Stefano, Bernardi M, Biselli M, Bernardi M, Biselli M, Caraceni P, Domenicali M, Garuti F, Gramenzi A, Lenzi B, Magalotti D, Cescon M, Ravaioli M, Del Poggio P, Olmi S, Rapaccini GL, Balsamo C, Di Nolfo MA, Vavassori E, Alberti A, Benvegnù L, Gatta A, Giacomin A, Vanin V, Pozzan C, Maddalo G, Giampalma E, Cappelli A, Golfieri R, Mosconi C, Renzulli M, Roselli P, Dell'Isola S, Ialungo AM, Risso D, Marenco S, Sammito G, Bruzzone L, Bosco G, Grieco A, Pompili M, Rinninella E, Siciliano M, Chiaramonte M, Guarino M, Cammà C, Maida M, Costantino A, Barcellona MR, Schiadà L, Gemini S, Lanzi A, Stefanini GF, Dall'Aglio AC, Cappa FM, Suzzi A, Mussetto A, Treossi O, Missale G, Porro E, Mismas V, Vivaldi C, Bolondi L, Zoli M, Granito A, Malagotti D, Tovoli F, Trevisani F, Venerandi L, Brandi G, Cucchetti A, Bugianesi E, Vanni E, Mezzabotta L, Cabibbo G, Petta S, Fracanzani A, Fargion S, Marra F, Fani B, Biasini E, Sacco R, CAPORASO, NICOLA, Colombo M, D'Ambrosio R, Crocè LS, Patti R, Giannini EG, Loria P, Lonardo A, Baldelli E, Miele L, Farinati F, Borzio M, Dionigi E, Soardo G, Caturelli E, Ciccarese F, Virdone R, Affronti A, Foschi FG, Borzio F., MORISCO, FILOMENA, Piscaglia, Fabio, Svegliati Baroni, Gianluca, Barchetti, Andrea, Pecorelli, Anna, Marinelli, Sara, Tiribelli, Claudio, Bellentani, Stefano, Bernardi M, Biselli M, Bernardi, M, Biselli, M, Caraceni, P, Domenicali, M, Garuti, F, Gramenzi, A, Lenzi, B, Magalotti, D, Cescon, M, Ravaioli, M, Del Poggio, P, Olmi, S, Rapaccini, Gl, Balsamo, C, Di Nolfo, Ma, Vavassori, E, Alberti, A, Benvegnù, L, Gatta, A, Giacomin, A, Vanin, V, Pozzan, C, Maddalo, G, Giampalma, E, Cappelli, A, Golfieri, R, Mosconi, C, Renzulli, M, Roselli, P, Dell'Isola, S, Ialungo, Am, Risso, D, Marenco, S, Sammito, G, Bruzzone, L, Bosco, G, Grieco, A, Pompili, M, Rinninella, E, Siciliano, M, Chiaramonte, M, Guarino, M, Cammà, C, Maida, M, Costantino, A, Barcellona, Mr, Schiadà, L, Gemini, S, Lanzi, A, Stefanini, Gf, Dall'Aglio, Ac, Cappa, Fm, Suzzi, A, Mussetto, A, Treossi, O, Missale, G, Porro, E, Mismas, V, Vivaldi, C, Bolondi, L, Zoli, M, Granito, A, Malagotti, D, Tovoli, F, Trevisani, F, Venerandi, L, Brandi, G, Cucchetti, A, Bugianesi, E, Vanni, E, Mezzabotta, L, Cabibbo, G, Petta, S, Fracanzani, A, Fargion, S, Marra, F, Fani, B, Biasini, E, Sacco, R, Morisco, Filomena, Caporaso, Nicola, Colombo, M, D'Ambrosio, R, Crocè, L, Patti, R, Giannini, Eg, Loria, P, Lonardo, A, Baldelli, E, Miele, L, Farinati, F, Borzio, M, Dionigi, E, Soardo, G, Caturelli, E, Ciccarese, F, Virdone, R, Affronti, A, Foschi, Fg, Borzio, F., Fabio Piscagliaxxx, Gianluca Svegliati-Baroni, Andrea Barchetti, Anna Pecorellixxx, Sara Marinellixxx, Claudio Tiribelli, and, Stefano Bellentani, on behalf of the HCC-NAFLD Italian Study Group [, Mauro Bernardi, Maurizio Biselli, Paolo Caraceni, Marco Domenicali, Francesca Garuti, Annagiulia Gramenzi, Barbara Lenzi, Donatella Magalotti, Matteo Cescon, Matteo Ravaioli, Emanuela Giampalma, Rita Golfieri, Cristina Mosconi, Luigi Bolondi, Marco Zoli, Alessandro Granito, Francesco Tovoli, Franco Trevisani, Laura Venerandi, Giovanni Brandi, Alessandro Cucchetti, ], DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE, Facolta' di MEDICINA e CHIRURGIA, AREA MIN. 06 - Scienze mediche, Da definire, Croce', Saveria, and HCC NAFLD Italian Study, Group

Subjects
Male, Cirrhosis, Survival, Chronic liver disease, Gastroenterology, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Nonalcoholic fatty liver disease, 80 and over, Prospective Studies, Chronic, Prospective cohort study, Aged, 80 and over, Medicine (all), Liver Neoplasms, hepatocellular carcinoma, Middle Aged, Hepatitis C, Liver Neoplasm, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Competing risk analysi, 030211 gastroenterology & hepatology, Female, Non Alcoholic SteatoHepatitis=NASH, Human, medicine.medical_specialty, Aged, Carcinoma, Hepatocellular, Hepatitis C, Chronic, Humans, Hepatology, Competing risk analysis, Milan criteria, 03 medical and health sciences, Internal medicine, medicine, Survival rate, business.industry, Settore MED/09 - MEDICINA INTERNA, Carcinoma, nutritional and metabolic diseases, Hepatocellular, medicine.disease, digestive system diseases, Nonalcoholic fatty liver disease, hepatocellular carcinoma, clinical patterns, business, clinical patterns
Abstract

none 31 no Nonalcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of metabolic syndrome and may evolve into hepatocellular carcinoma (HCC). Only scanty clinical information is available on HCC in NAFLD. The aim of this multicenter observational prospective study was to assess the clinical features of patients with NAFLD-related HCC (NAFLD-HCC) and to compare them to those of hepatitis C virus (HCV)-related HCC. A total of 756 patients with either NAFLD (145) or HCV-related chronic liver disease (611) were enrolled in secondary care Italian centers. Survival was modeled according to clinical parameters, lead-time bias, and propensity analysis. Compared to HCV, HCC in NAFLD patients had a larger volume, showed more often an infiltrative pattern, and was detected outside specific surveillance. Cirrhosis was present in only about 50% of NAFLD-HCC patients, in contrast to the near totality of HCV-HCC. Regardless of tumor stage, survival was significantly shorter (P = 0.017) in patients with NAFLD-HCC, 25.5 months (95% confidence interval 21.9-29.1), than in those with HCV-HCC, 33.7 months (95% confidence interval 31.9-35.4). To eliminate possible confounders, a propensity score analysis was performed, which showed no more significant difference between the two groups. Additionally, analysis of patients within Milan criteria submitted to curative treatments did not show any difference in survival between NAFLD-HCC and HCV-HCC (respectively, 38.6 versus 41.0 months, P = nonsignificant) CONCLUSIONS: NAFLD-HCC is more often detected at a later tumor stage and could arise also in the absence of cirrhosis, but after patient matching, it has a similar survival rate compared to HCV infection; a future challenge will be to identify patients with NAFLD who require more stringent surveillance in order to offer the most timely and effective treatment. Fabio Piscagliaxxx; Gianluca Svegliati-Baroni; Andrea Barchetti; Anna Pecorellixxx; Sara Marinellixxx; Claudio Tiribelli; and; Stefano Bellentani; on behalf of the HCC-NAFLD Italian Study Group [;Mauro Bernardi; Maurizio Biselli; Paolo Caraceni; Marco Domenicali; Francesca Garuti; Annagiulia Gramenzi; Barbara Lenzi; Donatella Magalotti; Matteo Cescon; Matteo Ravaioli; Emanuela Giampalma; Rita Golfieri; Cristina Mosconi; Luigi Bolondi; Marco Zoli; Alessandro Granito; Francesco Tovoli; Franco Trevisani; Laura Venerandi; Giovanni Brandi; Alessandro Cucchetti;] Fabio Piscagliaxxx; Gianluca Svegliati-Baroni; Andrea Barchetti; Anna Pecorellixxx; Sara Marinellixxx; Claudio Tiribelli; and; Stefano Bellentani; on behalf of the HCC-NAFLD Italian Study Group [;Mauro Bernardi; Maurizio Biselli; Paolo Caraceni; Marco Domenicali; Francesca Garuti; Annagiulia Gramenzi; Barbara Lenzi; Donatella Magalotti; Matteo Cescon; Matteo Ravaioli; Emanuela Giampalma; Rita Golfieri; Cristina Mosconi; Luigi Bolondi; Marco Zoli; Alessandro Granito; Francesco Tovoli; Franco Trevisani; Laura Venerandi; Giovanni Brandi; Alessandro Cucchetti;]

Published
2016

27. Estimation of lead-time bias and its impact on the outcome of surveillance for the early diagnosis of hepatocellular carcinoma

Author

Cucchetti A., Trevisani F., Pecorelli A., Erroi V., Farinati F., Ciccarese F., Rapaccini G. L., Di Marco M., Caturelli E., Giannini E. G., Zoli M., Borzio F., Cabibbo G., Felder M., Gasbarrini A., Sacco R., Foschi F. G., Missale G., Morisco F., Baroni G. S., Virdone R., Bernardi M., Pinna A. D., Bolondi L., Biselli M., Caraceni P., Garuti F., Gramenzi A., Lenzi B., Magalotti D., Piscaglia F., Serra C., Ravaioli M., Venerandi L., Del Poggio P., Olmi S., Balsamo C., Di Nolfo M. A., Vavassori E., Alberti A., Benvegnu L., Gatta A., Giacomin A., Vanin V., Pozzan C., Maddalo G., Giampalma E., Cappelli A., Golfieri R., Mosconi C., Renzulli M., Dell'Isola S., Ialungo A. M., Roselli P., Risso D., Marenco S., Sammito G., Bruzzone L., Bosco G., Grieco A., Pompili M., Rinninella E., Siciliano M., Chiaramonte M., Guarino M., Camma C., Maida M., Di Martino A., Barcellona M. R., Schiada L., Gemini S., Biasini E., Porro E., del Ricambio M., Mismas V., Vivaldi C., Cucchetti, A, Trevisani, F, Pecorelli, A, Erroi, V, Farinati, F, Ciccarese, F, Rapaccini, Gl, Di Marco, M, Caturelli, E, Giannini, Eg, Zoli, M, Borzio, F, Cabibbo, G, Felder, M, Gasbarrini, A, Sacco, R, Foschi, Fg, Missale, G, Morisco, Filomena, Baroni, G, Virdone, R, Bernardi, M, Pinna, Ad, Italian Liver Cancer, Group, Alessandro, Cucchetti, Franco, Trevisani, Anna, Pecorelli, Virginia, Erroi, Fabio, Farinati, Francesca, Ciccarese, Gian, Lodovico Rapaccini, Mariella Di, Marco, Eugenio, Caturelli, Edoardo, G. Giannini, Marco, Zoli, Franco, Borzio, Giuseppe, Cabibbo, Martina, Felder, Antonio, Gasbarrini, Rodolfo, Sacco, Francesco, Giuseppe Foschi, Gabriele, Missale, Filomena, Morisco, Gianluca, Svegliati Baroni, Roberto, Virdone, Mauro, Bernardi, Antonio D., Pinna, for the Italian Liver Cancer Group [.., Bolondi, Luigi, Maurizio, Biselli, Piscaglia, Fabio, ]., Cucchetti, A., Trevisani, F., Pecorelli, A., Erroi, V., Farinati, F., Ciccarese, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Giannini, E. G., Zoli, M., Borzio, F., Cabibbo, G., Felder, M., Gasbarrini, A., Sacco, R., Foschi, F. G., Missale, G., Morisco, F., Baroni, G. S., Virdone, R., Bernardi, M., Pinna, A. D., Bolondi, L., Biselli, M., Caraceni, P., Garuti, F., Gramenzi, A., Lenzi, B., Magalotti, D., Piscaglia, F., Serra, C., Ravaioli, M., Venerandi, L., Del Poggio, P., Olmi, S., Balsamo, C., Di Nolfo, M. A., Vavassori, E., Alberti, A., Benvegnu, L., Gatta, A., Giacomin, A., Vanin, V., Pozzan, C., Maddalo, G., Giampalma, E., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Dell'Isola, S., Ialungo, A. M., Roselli, P., Risso, D., Marenco, S., Sammito, G., Bruzzone, L., Bosco, G., Grieco, A., Pompili, M., Rinninella, E., Siciliano, M., Chiaramonte, M., Guarino, M., Camma, C., Maida, M., Di Martino, A., Barcellona, M. R., Schiada, L., Gemini, S., Biasini, E., Porro, E., del Ricambio, M., Mismas, V., and Vivaldi, C.

Subjects
Male, medicine.medical_specialty, Pediatrics, Carcinoma, Hepatocellular, Time Factors, Hepatocellular carcinoma, Settore MED/12 - GASTROENTEROLOGIA, Disease, Gastroenterology, Bias, Internal medicine, Overall survival, medicine, Humans, Early Detection of Cancer, Aged, Estimation, Surveillance, Hepatology, business.industry, Liver Neoplasms, medicine.disease, digestive system diseases, Lead time bias, Cirrhosis, Female, business, Lead-time bias, Follow-Up Studies
Abstract

Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. Background & Aims: Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. Methods: One-thousand three-hundred and eighty Child–Pugh class A/B patients from the ITA.LI.CA database, in whom HCC was detected during semiannual surveillance (n = 850), annual surveillance (n = 234) or when patients came when symptomatic (n = 296), were selected. Lead-time was estimated by means of appropriate formulas and Monte Carlo simulation, including 1000 patients for each arm. Results: The 5-year overall survival after HCC diagnosis was 32.7% in semiannually surveilled patients, 25.2% in annually surveilled patients, and 12.2% in symptomatic patients (p

Published
2014

28. A new marker for monitoring alcohol abuse? A pilot study on heavy drinkers

Author

INGEGNOLI A, BIASINI E, BONI I, ALTAVILLA N, LANDINI F, MERLI R, IORI V, ARAGONA G, CAVALLARO LG, MAINO M, FRANZ A, VESCOVI P, DI MARIO F., CAVESTRO , GIULIA MARTINA, Ingegnoli, A, Biasini, E, Boni, I, Altavilla, N, Landini, F, Merli, R, Iori, V, Cavestro, GIULIA MARTINA, Aragona, G, Cavallaro, Lg, Maino, M, Franz, A, Vescovi, P, and DI MARIO, F.

Published
2003

29. Exploring the role of MKK7 in excitotoxicity and cerebral ischemia: a novel pharmacological strategy against brain injury

Author

Vercelli, A, primary, Biggi, S, additional, Sclip, A, additional, Repetto, I E, additional, Cimini, S, additional, Falleroni, F, additional, Tomasi, S, additional, Monti, R, additional, Tonna, N, additional, Morelli, F, additional, Grande, V, additional, Stravalaci, M, additional, Biasini, E, additional, Marin, O, additional, Bianco, F, additional, di Marino, D, additional, and Borsello, T, additional

Published
2015
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32. Measurement of the Semileptonic Decays B --> D tau- nubar_tau and B --> D* tau- nubar_tau

Author

Aubert, B., Bona, M., Karyotakis, Y., P. Lees, J., Poireau, V., Prencipe, E., Prudent, X., Tisserand, V., Garra Tico, J., Grauges, E., Lopez, L., Palano, A., Pappagallo, M., Eigen, G., Stugu, B., Sun, Luyan, S. Abrams, G., Battaglia, M., N. Brown, D., G. Jacobsen, R., T. Kerth, L., G. Kolomensky, Yu., Lynch, G., L. Osipenkov, I., T. Ronan, M., Tackmann, K., Tanabe, T., M. Hawkes, C., Soni, N., T. Watson, A., Koch, H., Schroeder, T., J. Asgeirsson, D., G. Fulsom, B., Hearty, C., S. Mattison, T., A. Mckenna, J., Barrett, M., Khan, A., E. Blinov, V., D. Bukin, A., R. Buzykaev, A., P. Druzhinin, V., B. Golubev, V., P. Onuchin, A., I. Serednyakov, S., I. Skovpen, Yu., P. Solodov, E., Yu. Todyshev, K., Bondioli, M., Curry, S., Eschrich, I., Kirkby, D., J. Lankford, A., Lund, P., Mandelkern, M., C. Martin, E., P. Stoker, D., Abachi, S., Buchanan, C., Atmacan, H., W. Gary, J., Liu, Franklin, Long, O., M. Vitug, G., Yasin, Z., Zhang, L., Sharma, V., Campagnari, C., M. Hong, T., Kovalskyi, D., A. Mazur, M., D. Richman, J., W. Beck, T., M. Eisner, A., J. Flacco, C., Heusch, C.A., Kroseberg, J., S. Lockman, W., J. Martinez, A., Schalk, T., A. Schumm, B., Seiden, A., G. Wilson, M., O. Winstrom, L., H. Cheng, C., Doll, D.A., Echenard, B., Fang, F., G. Hitlin, D., Narsky, I., Piatenko, T., C. Porter, F., Andreassen, R., Mancinelli, G., T. Meadows, B., Mishra, K., D. Sokoloff, M., C. Bloom, P., T. Ford, W., Gaz, A., F. Hirschauer, J., Nagel, M., Nauenberg, U., G. Smith, J., R. Wagner, S., Ayad, R., Soffer, A., H. Toki, W., J. Wilson, R., Feltresi, E., Hauke, A., Jasper, H., Karbach, M., Merkel, J., Petzold, A., Spaan, B., Wacker, K., J. Kobel, M., Nogowski, R., R. Schubert, K., Schwierz, R., Volk, A., Bernard, D., R. Bonneaud, G., Latour, E., Verderi, M., J. Clark, P., Playfer, S., E. Watson, J., Andreotti, M., Bettoni, D., Bozzi, C., Calabrese, R., Cecchi, A., Cibinetto, G., Franchini, P., Luppi, E., Negrini, M., Petrella, A., Piemontese, L., Santoro, V., Baldini-Ferroli, R., Calcaterra, A., de Sangro, R., Finocchiaro, G., Pacetti, S., Patteri, P., M. Peruzzi, I., Piccolo, M., Rama, M., Zallo, A., Buzzo, A., Contri, R., Lo Vetere, M., M. Macri, M., R. Monge, M., Passaggio, S., Patrignani, C., Robutti, E., Santroni, A., Tosi, S., S. Chaisanguanthum, K., Morii, M., Adametz, A., Marks, J., Schenk, S., Uwer, U., Klose, V., M. Lacker, H., J. Bard, D., D. Dauncey, P., Tibbetts, M., K. Behera, P., Chai, X., J. Charles, M., Mallik, U., Cochran, J., B. Crawley, H., Dong, L., T. Meyer, W., Prell, S., I. Rosenberg, E., E. Rubin, A., Gao, Y.Y., V. Gritsan, A., J. Guo, Z., K. Lae, C., Arnaud, N., Béquilleux, J., d'Orazio, A., Davier, M., Firmino da Costa, J., Grosdidier, G., Le Diberder, F., Lepeltier, V., M. Lutz, A., Pruvot, S., Roudeau, P., H. Schune, M., Serrano, J., Sordini, V., Stocchi, A., Wormser, G., J. Lange, D., M. Wright, D., Bingham, I., P. Burke, J., Chavez, C.A., R. Fry, J., Gabathuler, E., Gamet, R., E. Hutchcroft, D., J. Payne, D., Touramanis, C., J. Bevan, A., K. Clarke, C., Di Lodovico, F., Sacco, R., Sigamani, M., Cowan, G., Paramesvaran, S., C. Wren, A., L. Davis, C., G. Denig, A., Fritsch, M., Gradl, W., E. Alwyn, K., Bailey, D., J. Barlow, R., Jackson, G., D. Lafferty, G., J. West, T., I. Yi, J., Anderson, J., Chen, C., Jawahery, A., Roberts, D.A., Simi, G., M. Tuggle, J., Dallapiccola, C., Li, Xiaojian, Salvati, E., Saremi, S., Cowan, R., Dujmic, D., H. Fisher, P., W. Henderson, S., Sciolla, G., Spitznagel, M., Taylor, F., K. Yamamoto, R., Zhao, M., M. Patel, P., H. Robertson, S., Lazzaro, A., Lombardo, V., Palombo, F., M. Bauer, J., Cremaldi, L., Godang, R., Kroeger, R., J. Summers, D., W. Zhao, H., Simard, M., Taras, P., Nicholson, H., de Nardo, G., Lista, L., Monorchio, D., Onorato, G., Sciacca, C., Raven, G., L. Snoek, H., P. Jessop, C., J. Knoepfel, K., M. Losecco, J., F. Wang, W., Corwin, L.A., Honscheid, K., Kagan, H., Kass, R., P. Morris, J., M. Rahimi, A., Regensburger, J.J., J. Sekula, S., K. Wong, Q., L. Blount, N., Brau, J., Frey, R., Igonkina, O., A. Kolb, J., Lu, M., Rahmat, R., B. Sinev, N., Strom, D., Strube, J., Torrence, E., Castelli, G., Gagliardi, N., Margoni, M., Morandin, M., Posocco, M., Rotondo, M., Simonetto, F., Stroili, R., Voci, C., del Amo Sanchez, P., Ben-Haim, E., Briand, H., Calderini, G., Chauveau, J., Hamon, O., Leruste, Ph., Ocariz, J., Perez, A., Prendki, J., Sitt, S., Gladney, L., Biasini E. Manoni, M., Angelini, C., Batignani, G., Bettarini, S., Carpinelli, M., Cervelli, A., Forti, F., A. Giorgi, M., Lusiani, A., Marchiori, G., Morganti, M., Neri, N., Paoloni, E., Rizzoab, G., Walsha, J.J., Lopes Pegna, D., Lu, C., Olsen, J., J. S. Smith, A., V. Telnov, A., Anulli, F., Baracchini, E., Cavoto, G., Faccini, R., Ferrarotto, F., Ferroni, F., Gaspero, M., D. Jacksona, P., Li Gioia, L., A. Mazzonia, M., Morgantia, S., Pireddaa, G., Rengaab, F., Voenaa, C., Ebert, M., Hartmann, T., Schöder, H., Waldi, R., Adye, T., Franek, B., O. Olaiya, E., F. Wilson, F., Emery, S., Escalier, M., Esteve, L., Hamel de Monchenault, G., Kozanecki, W., Vasseur, G., Yèche, Ch., Zito, M., R. Chen, X., Liu, Hong, Park, W., V. Purohit, M., M. White, R., R. Wilson, J., T. Allen, M., Aston, D., Bartoldus, R., F. Benitez, J., Cenci, R., P. Coleman, J., R. Convery, M., C. Dingfelder, J., Dorfan, J., P. Dubois-Felsmann, G., Dunwoodie, W., C. Field, R., M. Gabareen, A., T. Graham, M., Grenier, P., Hast, C., R. Innes, W., Kaminski, J., H. Kelsey, M., Kim, H., Kim, P., L. Kocian, M., W. G. S. Leith, D., Li, S., Lindquist, B., Luitz, S., Luth, V., L. Lynch, H., B. Macfarlane, D., Marsiske, H., Messner, R., R. Muller, D., Neal, H., Nelson, S., P. O'Grady, C., Ofte, I., Perl, M., N. Ratcliff, B., Roodman, A., A. Salnikov, A., H. Schindler, R., Schwiening, J., Snyder, A., Su, D., K. Sullivan, M., Suzuki, K., K. Swain, S., M. Thompson, J., Va'Vra, J., P. Wagner, A., Weaver, M., West, C.A., J. Wisniewski, W., Wittgen, M., H. Wright, D., W. Wulsin, H., K. Yarritu, A., Yi, K., C. Young, C., Ziegler, V., R. Burchat, P., J. Edwards, A., S. Miyashita, T., Ahmed, Mohamed-Salem, S. Alam, M., A. Ernst, J., Pan, B., A. Saeed, M., B. Zain, S., M. Spanier, S., J. Wogsland, B., Eckmann, R., L. Ritchie, J., M. Ruland, A., J. Schilling, C., F. Schwitters, R., W. Drummond, B., M. Izen, J., C. Lou, X., Bianchi, F., Gamba, D., Pelliccioni, M., Bomben, M., Bosisio, L., Cartaro, C., Della Ricca, G., Lanceri, L., Vitale, L., Azzolini, V., Lopez-March, N., Martinez-Vidal, F., Milanes, D.A., Oyanguren, A., Albert, J., Banerjee, Sw., Bhuyan, B., H. F. Choi, H., Hamano, K., Kowalewski, R., J. Lewczuk, M., M. Nugent, I., M. Roney, J., J. Sobie, R., J. Gershon, T., F. Harrison, P., Ilic, J., E. Latham, T., B. Mohanty, G., R. Band, H., Chen, X., Dasu, S., T. Flood, K., Pan, Y., Prepost, R., O. Vuosalo, C., L. Wu, S., Laboratoire d'Annecy de Physique des Particules (LAPP), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Laboratoire Leprince-Ringuet (LLR), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Laboratoire de l'Accélérateur Linéaire (LAL), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), Laboratoire de Physique Nucléaire et de Hautes Énergies (LPNHE), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, BABAR, Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], 12.15.Hh, 13.20.-v, 13.20.He, 14.40.Nd, 14.80.Cp, High Energy Physics::Experiment, High Energy Physics - Experiment
Abstract

We present measurements of the semileptonic decays B- --> D0 tau- nubar_tau, B- --> D*0 tau- nubar_tau, B0bar --> D+ tau- nubar_tau, and B0bar --> D*+ tau- nubar_tau, which are sensitive to non--Standard Model amplitudes in certain scenarios. The data sample consists of 232x10^6 Upsilon(4S) --> BBbar decays collected with the BaBar detector at the PEP-II e+e- collider. We select events with a D or D* meson and a light lepton (ell=e or mu) recoiling against a fully reconstructed B meson. We perform a fit to the joint distribution of lepton momentum and missing mass squared to distinguish signal B --> D(*) tau- nubar_tau (tau- --> ell- nubar_ell nu_tau) events from the backgrounds, predominantly B --> D(*) ell- nubar_ell. We measure the branching-fraction ratios R(D) == BR(B --> D tau- nubar_tau) / BR(B --> D ell- nubar_ell) and R(D*) == BR(B --> D* tau- nubar_tau) / BR(B --> D* ell- nubar_ell) and, from a combined fit to B- and B0bar channels, obtain the results R(D)=(41.6 +/- 11.7 +/- 5.2)% and R(D*)=(29.7 +/- 5.6 +/- 1.8)%, where the uncertainties are statistical and systematic. Normalizing to measured B- --> D(*)0 ell- nubar_ell branching fractions, we obtain BR(B --> D tau- nubar_tau)=(0.86 +/- 0.24 +/- 0.11 +/- 0.06)% and BR(B --> D* tau- nubar_tau)=(1.62 +/- 0.31 +/- 0.10 +/- 0.05)%, where the additional third uncertainty is from the normalization mode. We also present, for the first time, distributions of the lepton momentum, p*_ell, and the squared momentum transfer, q^2., Comment: 29 pages, 19 postscript figures, submitted to Phys. Rev. D

Published
2009
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33. Exclusive Initial-State-Radiation Production of the $D \bar D$, $D \bar D^*$, and $D^* \bar D^*$, Systems

Author

Aubert, B., Karyotakis, Y., P. Lees, J., Poireau, V., Prencipe, E., Prudent, X., Tisserand, V., Garra Tico, J., Grauges, E., Lopez, L., Palano, A., Pappagallo, M., Eigen, G., Stugu, B., Sun, Luyan, Battaglia, M., N. Brown, D., T. Kerth, L., G. Kolomensky, Yu., Lynch, G., L. Osipenkov, I., Tackmann, K., Tanabe, T., M. Hawkes, C., Soni, N., T. Watson, A., Koch, H., J. Asgeirsson, D., G. Fulsom, B., Hearty, C., S. Mattison, T., A. Mckenna, J., Barrett, M., Khan, A., Randle-Conde, A., E. Blinov, V., D. Bukin, A., R. Buzykaev, A., P. Druzhinin, V., B. Golubev, V., P. Onuchin, A., I. Serednyakov, S., I. Skovpen, Yu., P. Solodov, E., Yu. Todyshev, K., Bondioli, M., Curry, S., Eschrich, I., Kirkby, D., J. Lankford, A., Lund, P., Mandelkern, M., C. Martin, E., P. Stoker, D., Abachi, S., Buchanan, C., Atmacan, H., W. Gary, J., Liu, Franklin, Long, O., M. Vitug, G., Yasin, Z., Zhang, L., Sharma, V., Campagnari, C., M. Hong, T., Kovalskyi, D., A. Mazur, M., D. Richman, J., W. Beck, T., M. Eisner, A., Heusch, C.A., Kroseberg, J., S. Lockman, W., J. Martinez, A., Schalk, T., A. Schumm, B., Seiden, A., O. Winstrom, L., H. Cheng, C., Doll, D.A., Echenard, B., Fang, F., G. Hitlin, D., Narsky, I., Piatenko, T., C. Porter, F., Andreassen, R., Mancinelli, G., T. Meadows, B., Mishra, K., M. D. Sokoloff, And, C. Bloom, P., T. Ford, W., Gaz, A., F. Hirschauer, J., Nagel, M., Nauenberg, U., G. Smith, J., R. Wagner, S., Ayad, R., Soffer, A., H. Toki, W., J. Wilson, R., Feltresi, E., Hauke, A., Jasper, H., Karbach, M., Merkel, J., Petzold, A., Spaan, B., Wacker, K., J. Kobel, M., Nogowski, R., R. Schubert, K., Schwierz, R., Volk, A., Bernard , D., R. Bonneaud, G., Latour, E., Verderi, M., J. Clark, P., Playfer, S., E. Watson, J., Andreottia, M., Bettoni, D., Bozzi, C., Calabrese, R., Cecchi, A., Cibinetto, G., Franchini, P., Luppi, E., Negrini, M., Petrella, A., Piemontes, L., Santoro, V., Baldini-Ferroli, R., Calcaterra, A., De Sangro, R., Finocchiaro, G., Pacetti, S., Patteri, P., M. Peruzzi, I., Piccolo, M., Rama, M., Zallo, A., Contri, R., Guido, E., Lo Vetere, M., R. Monge, M., Passaggio, S., Patrignani, C., Robutti, E., Tosi, S., S. Chaisanguanthum, K., Morii, M., Adametz, A., Marks, J., Schenk, S., Uwer, U., U. Bernlochner, F., Klose, V., M. Lacker, H., J. Bard, D., D. Dauncey, P., Tibbetts, M., K. Behera, P., Chai, X., J. Charles, M., Mallik, U., Cochran, J., B. Crawley, H., Dong, L., T. Meyer, W., Prell, S., I. Rosenberg, E., E. Rubin, A., Gao, Y.Y., V. Gritsan, A., J. Guo, Z., Arnaud, N., Béquilleux, J., D'Orazio, A., Davier, M., Firmino Da Costa, J., Grosdidier, G., Le Diberder, F., Lepeltier, V., M. Lutz, A., Pruvot, S., Roudeau, P., H. Schune, M., Serrano, J., Sordini, V., Stocchi, A., Wormser, G., J. Lange, D., M. Wright, D., Bingham, I., P. Burke, J., Chavez, C.A., R. Fry, J., Gabathuler, E., Gamet, R., E. Hutchcroft, D., J. Payne, D., Touramanis, C., J. Bevan, A., K. Clarke, C., Di Lodovico, F., Sacco, R., Sigamani, M., Cowan, G., Paramesvaran, S., C. Wren, A., L. Davis, C., G. Denig, A., Fritsch, M., Gradl, W., Hafner, A., E. Alwyn, K., Bailey, D., J. Barlow, R., Jackson, G., D. Lafferty, G., J. West, T., I. Yi, J., Anderson, J., Chen, C., Jawahery, A., Roberts, D.A., Simi, G., M. Tuggle, J., Dallapiccola, C., Salvati, E., Saremi, S., Cowan, R., Dujmic, D., H. Fisher, P., W. Henderson, S., Sciolla, G., Spitznagel, M., K. Yamamoto, R., Zhao, M., M. Patel, P., H. Robertson, S., Schram, M., Lazzaroab, A., Lombardoa, V., Palomboab, F., Stracka, S., M. Bauer, J., Cremaldi, L., Godang, R., Kroeger, R., J. Summers, D., W. Zhao, H., Simard, M., Taras, P., Nicholson, H., De Nardo, G., Lista, L., Monorchio, D., Onorato, G., Sciacca, C., Raven, G., L. Snoek, H., P. Jessop, C., J. Knoepfel, K., M. Losecco, J., F. Wang, W., Corwin, L.A., Honscheid, K., Kagan, H., Kass, R., P. Morris, J., M. Rahimi, A., Regensburger, J.J., J. Sekula, S., K. Wong, Q., L. Blount, N., Brau, J., Frey, R., Igonkina, O., A. Kolb, J., Lu, M., Rahmat, R., B. Sinev, N., Strom, D., Strube, J., Torrence, E., Castelli, G., Gagliardi, N., Margoni, M., Morandin, M., Posocca, M., Rotondo, M., Simonetto, F., Stroili, R., Voci, C., Del Amo Sanchez, P., Ben-Haim, E., Briand, H., Chauveau, J., Hamon, O., Leruste, Ph., Ocariz, J., Perez, A., Prendki, J., Sitt, S., Gladney, L., Biasini E. Manoni, M., Angelini, C., Batignani, G., Bettarini, S., Calderini, G., Carpinelli, M., Cervelli, A., Forti, F., A. Giorgi, M., Lusiani, A., Marchiori, G., Morganti, M., Neri, N., Paoloni, E., Rizzo, G., J. Walsh, J., Lopes Pegna, D., Lu, C., Olsen, J., J. S. Smith, A., V. Telnov, A., Anulli, F., Baracchini, E., Cavoto, G., Faccini, R., Ferrarotto, F., Ferroni, F., Gaspero, M., D. Jacksona, P., Li Gioia, L., A. Mazzoni, M., Morganti, S., Piredda, G., Renga, F., Voena, C., Ebert, M., Hartmann, T., Schröder, H., Waldi, R., Adye, T., Franek, B., O. Olaiya, E., F. Wilson, F., Emery, S., Esteve, L., Hamel De Monchenault, G., Kozanecki, W., Vasseur, G., Yèche, Ch., Zito, M., R. Chen, X., Liu, Hong, Park, W., V. Purohit, M., M. White, R., R. Wilson, J., T. Allen, M., Aston, D., Bartoldus, R., F. Benitez, J., Cenci, R., P. Coleman, J., R. Convery, M., C. Dingfelder, J., Dorfan, J., P. Dubois-Felsmann, G., Dunwoodie, W., C. Field, R., M. Gabareen, A., T. Graham, M., Grenier, P., Hast, C., R. Innes, W., Kaminski, J., H. Kelsey, M., Kim, H., Kim, P., L. Kocian, M., W. G. S. Leith, D., Li, S., Lindquist, B., Luitz, S., Luth, V., L. Lynch, H., B. Macfarlane, D., Marsiske, H., Messner, R., R. Muller, D., Neal, H., Nelson, S., P. O'Grady, C., Ofte, I., Perl, M., N. Ratcliff, B., Roodman, A., A. Salnikov, A., H. Schindler, R., Schwiening, J., Snyder, A., Su, D., K. Sullivan, M., Suzuki, K., K. Swain, S., M. Thompson, J., Va'Vra, J., P. Wagner, A., Weaver, M., West, C.A., J. Wisniewski, W., Wittgen, M., H. Wright, D., W. Wulsin, H., K. Yarritu, A., Yi, K., C. Young, C., Ziegler, V., R. Burchat, P., J. Edwards, A., S. Miyashita, T., Ahmed, Mohamed-Salem, S. Alam, M., A. Ernst, J., Pan, B., A. Saeed, M., B. Zain, S., M. Spanier, S., J. Wogsland, B., Eckmann, R., L. Ritchie, J., M. Ruland, A., J. Schilling, C., F. Schwitters, R., W. Drummond, B., M. Izen, J., C. Lou, X., Bianchi, F., Gamba, D., Pelliccioni, M., Bomben, M., Bosisio, L., Cartaro, C., Della Ricca, G., Lancer, L., Vitale, L., Azzolini, V., Lopez-March, N., Martinez-Vidal, F., Milanes, D.A., Oyanguren, A., Kowalewski, R., J. Lewczuk, M., M. Nugent, I., M. Roney, J., J. Sobie, R., J. Gershon, T., F. Harrison, P., Ilic, J., E. Latham, T., B. Mohanty, G., M. T. Puccio, E., R. Band, H., Chen, X., Dasu, S., T. Flood, K., Pan, Y., Prepost, R., O. Vuosalo, C., L. Wu, S., Schroeder, T., Laboratoire d'Annecy de Physique des Particules (LAPP), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Laboratoire Leprince-Ringuet (LLR), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de l'Accélérateur Linéaire (LAL), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Nucléaire et de Hautes Énergies (LPNHE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, BABAR, Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
High Energy Physics - Experiment (hep-ex), High Energy Physics::Phenomenology, [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], FOS: Physical sciences, High Energy Physics::Experiment, High Energy Physics - Experiment
Abstract

We perform a study of the exclusive production of $D \bar D$, $D \bar D^*$, and $D^* \bar D^*$ in initial-state-radiation events, from $e^+ e^-$ annihilations at a center-of-mass energy near 10.58 GeV, to search for charmonium and possible new resonances. The data sample corresponds to an integrated luminosity of 384 $fb^{-1}$ and was recorded by the BaBar experiment at the PEP-II storage rings. The $D \bar D$, $D \bar D^*$, and $D^* \bar D^*$ mass spectra show clear evidence of several $\psi$ resonances. However, there is no evidence for $Y(4260) \to D \bar D^*$ or $Y(4260)\to D^* \bar D^*$., Comment: 16 pages, 8 tables, 13 postscript figures, submitted to Phys. Rev. D

Published
2009
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37. The safety of Sonovue in abdominal applications: retrospective analysis of 23188 investigations

Author

Piscaglia, F, Bolondi, L, Italian Society for Ultrasound in Medicine, Aiani, Biology Study Group on Ultrasound Contrast Agents 1 L., Luigi Angeli, M., Arienti, V., Barozzi, L., Basilico, R., Bertolotto, M., Biasini, E., Busilacchi, P., Calliada, F., Caremani, * M., Caturelli, E., Celli, N., Colecchia, A., Cova, L., Assunta Cova, M., Crocetti, L., de Sio, I., Drudi, Francesco Maria, Ferraioli, G., Filice, C., Fornari, F., Gaiani, S., Giangregorio, F., Giorgio, A., Ierace, T., Lencioni, R., Livraghi, T., Magnolfi, F., Martegani, A., Meloni, F., Menozzi, G., Pelosi, G., Pompili, M., Riccardi, L., Ricci, P., Rubaltelli, L., Sacerdoti, D., Serafini, G., Serra, C., Solbiati, L., Tacconi, D., Valentino, M., Vidili, G., Vitali, F., Piscaglia F., Bolondi L., and Italian Society for Ultrasound in Medicine and Biology (SIUMB) Study Group on Ultrasound Contrast Agents.

Subjects
medicine.medical_specialty, Acoustics and Ultrasonics, Sulfur Hexafluoride, Biophysics, Contrast Media, Abdomen, medicine, Retrospective analysis, Adverse Drug Reaction Reporting Systems, Humans, Radiology, Nuclear Medicine and imaging, Adverse effect, Phospholipids, Retrospective Studies, Ultrasonography, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Magnetic resonance imaging, Retrospective cohort study, Safety profile, medicine.anatomical_structure, Liver, Abdominal examination, Radiology, business
Abstract

The aim of the present retrospective study was to assess the incidence of adverse events (AE) of a second-generation ultrasound contrast agent in real clinical practice. A total of 28 Italian Centres provided data on the postmarketing use of SonoVue (Bracco Spa, Milan, Italy) in abdominal examination performed between December 2001 and December 2004. A total of 23 188 investigations were reported. No fatal event occurred. AEs were reported in 29 cases, of which only two were graded as serious; the rest, 27, were nonserious (23 mild, three moderate and one severe). The overall reporting rate of serious AE was 0.0086%. Overall, only four AEs required treatment (two serious, two nonserious including one moderate and one severe AEs). In conclusion, the present large-scale retrospective analysis showed that SonoVue has a good safety profile in abdominal applications, with an AE reporting rate lower than or similar to that reported for radiologic and magnetic resonance contrast agents.

Published
2006

38. Proteasome inhibition and aggregation in Parkinson's disease: a comparative study in untransfected and transfected cells

Author

Biasini, E., Fioriti, L., Ceglia, I., Invernizzi, R., Bertoli, Alessandro, Chiesa, R., and Forloni, G.

Subjects
Proteasome Endopeptidase Complex, Leupeptins, Parkinson's disease, Ubiquitin-Protein Ligases, Synucleins, Nerve Tissue Proteins, Parkinson Disease, Transfection, PC12 Cells, Rats, mesencephalic cultures, Rats, Sprague-Dawley, Cysteine Endopeptidases, synuclein, Mesencephalon, Multienzyme Complexes, parkin, protein misfolding, ubiquitin-proteasome, alpha-Synuclein, Animals, Humans, RNA, Messenger, Cell Aggregation
Abstract

Dysfunction of the ubiquitin-proteasome system (UPS) has been implicated in Parkinson's disease (PD) and other neurodegenerative disorders. We have investigated the effect of UPS inhibition on the metabolism of alpha-synuclein (SYN) and parkin, two proteins genetically and histopathologically associated to PD. Pharmacological inhibition of proteasome induced accumulation of both parkin and SYN in transfected PC12 cells. We found that this effect was caused by increased protein synthesis rather than impairment of protein degradation, suggesting that inhibition of the UPS might lead to non-specific up-regulation of cytomegalovirus (CMV)-driven transcription. To investigate whether endogenous parkin and SYN can be substrate of the UPS, untransfected PC12 cells and primary mesencephalic neurones were exposed to proteasome inhibitors, and parkin and SYN expression was evaluated at both protein and mRNA level. Under these conditions, we found that proteasome inhibitors did not affect the level of endogenous parkin and SYN. However, we confirmed that dopaminergic neurones were selectively vulnerable to the toxicity of proteasome inhibitors. Our results indicate that studies involving the use of proteasome inhibitors, particularly those in which proteins are expressed from a heterologous promoter, are subjected to potential artefacts that need to be considered for the interpretation of the role of UPS in PD pathogenesis.

Published
2004

39. Role of lipid rafts and GM1 in the segregation and processing of Prion Protein

Author

Botto, L, Cunati, D, Coco, S, Sesana, M, Bulbarelli, A, Biasini, E, Colombo, L, Negro, A, Chiesa, R, Masserini, M, Palestini, P, BOTTO, LAURA MARIA, CUNATI, DIANA, COCO, SILVIA, SESANA, MARIA SILVIA, BULBARELLI, ALESSANDRA, MASSERINI, MASSIMO ERNESTO, PALESTINI, PAOLA NOVERINA ADA, Botto, L, Cunati, D, Coco, S, Sesana, M, Bulbarelli, A, Biasini, E, Colombo, L, Negro, A, Chiesa, R, Masserini, M, Palestini, P, BOTTO, LAURA MARIA, CUNATI, DIANA, COCO, SILVIA, SESANA, MARIA SILVIA, BULBARELLI, ALESSANDRA, MASSERINI, MASSIMO ERNESTO, and PALESTINI, PAOLA NOVERINA ADA

Published
2014

42. Raccomandazioni sul trattamento del paziente odontoiatrico in terapia anticoagulante

Author

Adrario, E., Alberton, M., Antonimi, M., Barbieri, A., Bazzato, Mf, Biasini, E., Bosco, M., Boscolo, I., Bozza, R., Camaioni, D., DA CORTE, S., DI MASSA, A., Dpl, Diana, Favaro, R., Giacomo, Favero, Giovanni, Bavero, Floreani, S., Ghiotto, Pg, Lorenzi, P., Manani, G., Marino, D., Mazzuchin, M., Olivi, R., Petrini, F., Risita, M., Rizzo, F., Ruffato, L., Ruggi, M., Ruzza, C., Semenzato, E., Stifano, M., Tognazzo, F., Tommasino, C., Tonello, S., Trevisan, A., Vellardi, P., and Zanette, Gastone

Published
2003

43. RACCOMANDAZIONI SULLE CARATTERISTICHE DELL'AMBULATORIO ODONTOIATRICO IN RELAZIONE ALL'EROGAZIONE DI INTERVENTI DI ANESTESIA ODONTOSTOMATOLOGICA EFFETTUATI IN ANSIOLISI

Author

Adrario, E., Alberton, M., Antonimi, M., Barbieri, A., Bazzato, Mf, Biasini, E., Bosco, M., Boscolo, I., Bozza, R., Camaioni, D., DA CORTE, S., DI MASSA, A., Dpl, Diana, Favaro, R., Giacomo, Favero, Giovanni, Bavero, Floreani, S., Ghiotto, Pg, Lorenzi, P., Manani, G., Marino, D., Mazzuchin, M., Olivi, R., Petrini, F., Risita, M., Rizzo, F., Ruffato, L., Ruggi, M., Ruzza, C., Semenzato, E., Stifano, M., Tognazzo, F., Tommasino, C., Tonello, S., Trevisan, A., Vellardi, P., and Zanette, Gastone

Published
2003

44. A Mutant Prion Protein Sensitizes Neurons to Glutamate-Induced Excitotoxicity

Author

Biasini, E., primary, Unterberger, U., additional, Solomon, I. H., additional, Massignan, T., additional, Senatore, A., additional, Bian, H., additional, Voigtlaender, T., additional, Bowman, F. P., additional, Bonetto, V., additional, Chiesa, R., additional, Luebke, J., additional, Toselli, P., additional, and Harris, D. A., additional

Published
2013
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