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13 results on '"Riccardi Laura"'

1. Abietane-Type Diterpenoids Inhibit Protein Tyrosine Phosphatases by Stabilizing an Inactive Enzyme Conformation

Author

Hjortness, Michael K, Riccardi, Laura, Hongdusit, Akarawin, Ruppe, Sophia, Zhao, Mengxia, Kim, Edward Y, Zwart, Peter H, Sankaran, Banumathi, Arthanari, Haribabu, Sousa, Marcelo C, De Vivo, Marco, and Fox, Jerome M

Subjects
Biochemistry and Cell Biology, Medicinal and Biomolecular Chemistry, Chemical Sciences, Biological Sciences, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Generic health relevance, Abietanes, Humans, Models, Molecular, Molecular Dynamics Simulation, Nuclear Magnetic Resonance, Biomolecular, Protein Domains, Protein Folding, Protein Kinase Inhibitors, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Medical Biochemistry and Metabolomics, Biochemistry & Molecular Biology, Biochemistry and cell biology, Medical biochemistry and metabolomics, Medicinal and biomolecular chemistry
Abstract

Protein tyrosine phosphatases (PTPs) contribute to a striking variety of human diseases, yet they remain vexingly difficult to inhibit with uncharged, cell-permeable molecules; no inhibitors of PTPs have been approved for clinical use. This study uses a broad set of biophysical analyses to evaluate the use of abietane-type diterpenoids, a biologically active class of phytometabolites with largely nonpolar structures, for the development of pharmaceutically relevant PTP inhibitors. Results of nuclear magnetic resonance analyses, mutational studies, and molecular dynamics simulations indicate that abietic acid can inhibit protein tyrosine phosphatase 1B, a negative regulator of insulin signaling and an elusive drug target, by binding to its active site in a non-substrate-like manner that stabilizes the catalytically essential WPD loop in an inactive conformation; detailed kinetic studies, in turn, show that minor changes in the structures of abietane-type diterpenoids (e.g., the addition of hydrogens) can improve potency (i.e., lower IC50) by 7-fold. These findings elucidate a previously uncharacterized mechanism of diterpenoid-mediated inhibition and suggest, more broadly, that abietane-type diterpenoids are a promising source of structurally diverse-and, intriguingly, microbially synthesizable-molecules on which to base the design of new PTP-inhibiting therapeutics.

Published
2018

2. Liver Transplantation in Patients with Alcoholic Liver Disease: A Retrospective Study

Author

Vassallo, Gabriele A., Tarli, Claudia, Rando, Maria Margherita, Mosoni, Carolina, Mirijello, Antonio, Agyei-Nkansah, Adwoa, Antonelli, Mariangela, Sestito, Luisa, Perotti, Germano, Di Giuda, Daniela, Agnes, Salvatore, Grieco, Antonio, Gasbarrini, Antonio, Addolorato, Giovanni, Abbate, Valeria, Ainora, Maria Elena, Annicchiarico, Brigida Eleonora, Avolio, Alfonso Wolfango, Biolato, Marco, Calia, Rosaria, De Matthaeis, Nicoletta, Cristina d'Angelo, Null, Ferrarese, Daniele, Ferrulli, Anna, Garcovich, Matteo, Frongillo, Francesco, Marrone, Giuseppe, Miele, Luca, Nure, Eda, Pietrogiacomi, Paola, Pizzolante, Fabrizio, Pompili, Maurizio, Ponziani, Francesca Romana, Rapaccini, Gian Ludovico, Riccardi, Laura, Rinninella, Emanuele, Sganga, Gabriele, Siciliano, Massimo, and Zocco, Maria Assunta

Subjects
Liver Cirrhosis, Male, Alcoholic liver disease, Cirrhosis, medicine.medical_treatment, Settore MED/18 - CHIRURGIA GENERALE, Medicine (miscellaneous), Kaplan-Meier Estimate, Liver transplantation, Toxicology, Gastroenterology, Liver disease, 0302 clinical medicine, Postoperative Complications, Liver Cirrhosis, Alcoholic, Recurrence, Cause of Death, Alcoholic Liver Diseases | Liver Transplantation | Alcohol Abstinence, Alcohol Abstinence, Liver Diseases, Graft Survival, Liver Neoplasms, General Medicine, Middle Aged, Alcoholic, surgical procedures, operative, Psychiatry and Mental Health, 030211 gastroenterology & hepatology, Female, Adult, Reoperation, medicine.medical_specialty, Liver tumor, 03 medical and health sciences, Internal medicine, Aged, Follow-Up Studies, Humans, Liver Diseases, Alcoholic, Liver Transplantation, Retrospective Studies, Survival Analysis, medicine, Survival rate, business.industry, Postoperative complication, medicine.disease, Transplantation, business, 030217 neurology & neurosurgery
Abstract

Aim Alcoholic liver disease (ALD) is the most common liver disease in the Western World. Liver transplantation (LT) is the treatment for end-stage ALD. However, many transplant centers are still reluctant to transplant these patients because of the risk of alcohol relapse, recurrence of the primary liver disease and associated post-transplant complications. We examined survival rate, prevalence of primary liver disease recurrence, re-transplantation and post-transplant complications among transplanted patients for alcoholic cirrhosis compared with those transplanted for viral cirrhosis. Methods data about patients transplanted for alcoholic and viral cirrhosis at the Gemelli Hospital from January 1995 to April 2016 were retrospectively collected. Survival rate was evaluated according to the Kaplan-Meier method. Recurrence was defined as histological evidence of primary liver disease. Data on the onset of complication, causes of death and graft failure after liver transplant were analyzed. Results There was no statistically significant difference regarding survival rate between the two groups. Only patients transplanted for viral cirrhosis presented with primary liver disease recurrence. There was a higher rate of cancer development in patients transplanted for alcoholic cirrhosis. Cancer was the major cause of death in this population. Risk factors associated with the onset of cancer were a high MELD score at the transplant time and smoking after transplantation. Conclusion ALD is a good indication for LT. Patients transplanted for alcoholic cirrhosis should receive regular cancer screening and should be advised against smoking. Short summary No difference was found between patients transplanted for alcoholic cirrhosis and viral cirrhosis in term of survival rate. Only patients transplanted for viral cirrhosis presented primary liver disease recurrence. A higher rate of cancer development was found in patients transplanted for alcoholic cirrohosis. This complication was associated with post-trasplant smoking.

Published
2018

3. Single hepatocellular carcinoma smaller than 2 cm: are ethanol injection and radiofrequency ablation equally effective?

Author

Pompili, Maurizio, Matthaeis, Nicoletta, Saviano, Antonio, Sio, Ilario, Francica, Giampiero, Brunello, Franco, Cantamessa, Alessandro, Giorgio, Antonio, Scognamiglio, Umberto, Fornari, Fabio, Giangregorio, Francesco, Fabio Piscaglia, Gualandi, Silvia, Caturelli, Eugenio, Roselli, Paola, Riccardi, Laura, Rapaccini, Gian Ludovico, Pompili, Maurizio, De Matthaeis, Nicoletta, Saviano, Antonio, De Sio, Ilario, Francica, Giampiero, Brunello, Franco, Cantamessa, Alessandro, Giorgio, Antonio, Scognamiglio, Umberto, Fornari, Fabio, Giangregorio, Francesco, Piscaglia, Fabio, Gualandi, Silvia, Caturelli, Eugenio, Roselli, Paola, Riccardi, Laura, and Rapaccini, Gian Ludovico

Subjects
Adult, Male, Carcinoma, Hepatocellular, Hepatocellular carcinoma, Prognosi, liver cirrhosis, Settore MED/12 - GASTROENTEROLOGIA, overall survival, Antineoplastic Agents, Injections, Intralesional, Antineoplastic Agent, Retrospective Studie, Humans, neoplasms, Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA, Aged, Proportional Hazards Models, Retrospective Studies, Aged, 80 and over, Ethanol, liver cirrhosi, Settore MED/09 - MEDICINA INTERNA, Liver Neoplasms, Middle Aged, Prognosis, tumor recurrence, digestive system diseases, Tumor Burden, surgical procedures, operative, Liver Neoplasm, Proportional Hazards Model, Catheter Ablation, Female, radiofrequency ablation, Neoplasm Recurrence, Local, percutaneous ethanol injection, Human
Abstract

The impact of radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) on survival in patients with small hepatocellular carcinoma (HCC) is unclear. We compared their efficacy in cirrhotics with single HCC ≤2 cm.Two hundred forty-four cirrhotics with single HCC ≤2 cm treated with PEI (108 cases) or RFA (136 cases) were enrolled in the study. Eighty-one patients in each group were selected for propensity score matching analysis.The five-year survival was not significantly different (64.7% in PEI and 72.9% in RFA group) but the 5-year recurrence (73.3% in PEI and 49% in RFA group, p=0.023) and local tumor progression (49% in PEI and 30.1% in RFA group, p=0.018) were higher in the PEI group.PEI and RFA are equally effective in treating HCCs smaller than 2 cm in terms of 5-year survival, despite higher cumulative and local recurrence rates, in patients treated with PEI.

Published
2015

4. Non Alcoholic Fatty Liver Disease is Associated with Increased GHBP and Reduced GH/IGF-I Levels

Author

Fusco, Alessandra, Miele, Luca, D'Uonnolo, A, Forgione, Alessandra, Riccardi, Laura, Cefalo, Consuelo, Barini, Angelina, Bianchi, Alfredo, Giampietro, A, Cimino, V, Landolfi, Raffaele, Grieco, Alessandro, and De Marinis, L.

Subjects
Adult, Blood Glucose, Male, GHBP, NAFLD, GH, Obesity, IGFBP-3, Settore MED/09 - MEDICINA INTERNA, Settore MED/13 - ENDOCRINOLOGIA, Middle Aged, nafld, Fatty Liver, Insulin-Like Growth Factor Binding Proteins, Cross-Sectional Studies, Non-alcoholic Fatty Liver Disease, Growth Hormone, Humans, Female, Insulin-Like Growth Factor I, Carrier Proteins, Glycoproteins
Abstract

Nonalcoholic fatty liver disease (NAFLD) has been described in adult GH deficiency syndrome. Furthermore, chronic liver disease can be associated with significant changes in levels of IGF-I, GH-binding protein (GHBP), IGF-binding proteins (IGFBPs) and acid-labile subunit (ALS). However, the effect of liver steatosis on the GHBP production has not been investigated yet.To explore whether GH secretion and/or levels of IGF-I, IGFBP-3, ALS and GHBP could be altered in obese patients in relation to the presence of liver steatosis.A total of 115 obese patients (BMI30) were enrolled in the protocol (65 patients with liver steatosis and 50 age- and BMI-matched controls). In all patients, the following parameters were studied: serum levels of glucose, insulin, the HOMA index, IGF-I, GHBP, IGFBP-3, ALS and GH after GHRH and arginine stimulation test.As expected, patients with NAFLD had blood glucose, insulin, HOMA-R significantly higher than controls, indicating a more severe insulin-resistance state in NAFLD. Furthermore, patients with NAFLD had higher levels of GHBP and IGFBP-3 and lower GH peak and IGF-I levels as compared to controls. No difference was found in ALS levels between the groups. In a multivariate analysis, GHBP was positively associated with hepatic steatosis while IGF-1 was negatively associated with hepatic steatosis.This study demonstrates that in patients with NAFLD, the GHBP levels are increased, and that the GH/IGF-I axis is significantly altered probably leading to reduced IGF-I bioavailability at tissue level.

Published
2011

5. Ethanol injection is highly effective for hepatocellular carcinoma smaller than 2 cm

Author

Pompili, Maurizio, Nicolardi, Erica, Abbate, Valeria, Miele, Luca, Riccardi, Laura, Covino, Marcello, De Matthaeis, Nicoletta, Grieco, Alessandro, Landolfi, Raffaele, and Rapaccini, Gl

Subjects
Adult, Aged, 80 and over, Male, Carcinoma, Hepatocellular, Ethanol, Brief Article, Settore MED/09 - MEDICINA INTERNA, Liver Neoplasms, Middle Aged, digestive system diseases, Disease-Free Survival, Injections, Cohort Studies, Survival Rate, Treatment Outcome, Humans, Female, Aged
Abstract

To analyze the long-term prognosis in a cohort of western cirrhotic patients with single hepatocellular carcinoma treated with ethanol injection.One-hundred forty-eight patients with solitary hepatocellular carcinoma were enrolled. The tumor diameter was lower than 2 cm in 47 patients but larger in the remaining 101 patients. The impact of some pre-treatment clinical and laboratory parameters and of tumor recurrence on patients' survival was assessed.Among the pre-treatment parameters, only a tumor diameter of less than 2 cm was an independent prognostic factor of survival. The occurrence of new nodules in other liver segments and the neoplastic portal invasion were linked to a poorer prognosis at univariate analysis. Patients with a single hepatocellular carcinoma smaller than 2 cm showed a better 5-year cumulative survival (73.0% vs 47.9%) (P = 0.009), 3-year local recurrence rate (29.1% vs 51.5%) (P = 0.011), and 5-year distant intrahepatic recurrence rate (52.9% vs 62.8%) (P = 0.054) compared to patients with a larger tumor.The 5-year survival rate of patients with single hepatocellular carcinoma2 cm undergoing ethanol injection is excellent and comparable to that achieved using radiofrequency ablation.

Published
2010

6. Elastography assessment in patients with chronic HCV infection

Author

Abenavoli, L, Addolorato, Giovanni, Riccardi, Laura, Gasbarrini, Antonio, Gasbarrini, Giovanni Battista, and Rapaccini, Gl

Subjects
Liver Cirrhosis, Settore MED/12 - GASTROENTEROLOGIA, Elasticity Imaging Techniques, Humans, Hepatitis C, Chronic, Sensitivity and Specificity
Abstract

Liver fibrosis (LB) assessment plays an important role in hepatology. A common characteristic of all chronic liver diseases is the occurrence and progression of fibrosis towards cirrhosis. Besides its plain interest for prognosis purposes, determining the fibrosis reveals the natural history of the disease and the risk factors associated with its progression to guide the antifibrotic action of different treatments.Today, in clinical practice there are three available methods for the evaluation of LB. Biopsy, which is still considered as the 'gold standard' method. Serological markers and their mathematical combination are suggested in the last years in alternative to LB. More recently, transient elastography (TE) was proposed. TE is a simple and noninvasive method for measuring liver stiffness. This technique is based on the progression speed of an elastic shear wave within the liver.Currently, there are just a few studies capable of evaluating the TE effectiveness in chronic liver diseases, mainly in patients infected with hepatitis C virus (HCV). Its application must also be studied in the monitoring of patients suffering from chronic HCV infection and subjected to a treatment that can modify their degree of liver fibrosis. The results of TE must be interpreted according to the clinical background of the specialist.

Published
2008

7. Platelet count does not predict bleeding in cirrhotic patients: Results from the PRO-LIVER Study

Author

Basili, S. a, Raparelli, V. b., Napoleone, L. b., Talerico, G. a., Corazza, G. R. c., Perticone, F. d., Sacerdoti, D. e., Andriulli, A. f., Licata, A. g., Pietrangelo, A., Picardi, A. i., Raimondo, G. j., Violi, F., Palasciano, G., D’Alitto, F., Palmieri, V. O., Santovito, D., Michele, Di, Croce, D., Brocco, G., Fasolato, S., Cecchetto, S., Bombonato, L., Bertoni, G., Restuccia, M., Andreozzi, T., Liguori, P., Caroleo, M. L., Perticone, B., Staltari, M., Manfredini, O., Giorgi, De, Averna, A., Giammanco, M., Granito, A., Pettinari, A., Marinelli, I., Bolondi, S., Falsetti, L., Salvi, L., Durante-Mangoni, A., Cesaro, E., Farinaro, F., Ragone, V., Morana, E., Ippolito, I., Iacobellis, A., Niro, A., Merla, G., Maimone, A., Cacciola, S., Varvara, I., Drenaggi, D., Staffolani, D., Vespasiani-Gentilucci, S., Galati, U., Gallo, G., Davì, P., Schiavone, G., Santilli, C., Tana, F., Soresi, C., Bianchi, Giovanni, Carderi, B., Pinto, I., Tuttolomondo, A., Ferrari, A., Gresele, G., Fierro, P., Morelli, T., Laffi, O., Romanelli, G., Arena, R. G., Stasi, U., Gasbarrini, A., Garcovich, M., Zocco, M. A., Riccardi, L., Ainora, M. E., Capeci, W., Martino, Giuseppe, Nobili, P., Cavallo, L., Frugiuele, M., Greco, P., Ventura, P., Cuoghi, C., Marcacci, M., Serviddio, G., Vendemiale, G., Villani, R., Gargano, R., Vidili, G., Cesare, Di, Masala, V., Delitala, M., Invernizzi, G., Vincenzo, P., Minno, Di, Tufano, G., Purrello, A., Privitera, F., Forgione, G., Curigliano, A., Senzolo, V., Rodríguez-Castro, M., Giannelli, K. I., Serra, G., Neri, C., Pignataro, S., Rizzetto, P., Debernardi, M., Svegliati, V. W., Bergamaschi, B. G., Masotti, G., Costanzo, M., Antonio, F., Angelico, F., Del, Ben, Polimeni, M., Proietti, L., Cangemi, M., Romiti, R., Toriello, G. F., Sperduti, F., Santangelo, N., Visioli, G., Todisco, G., Vestri, Anna, Farcomeni, R., Corrao, A., Gobbi, S., Corradini, E., Costantino, G., Tripepi, G., Angelico, M., Bolondi, L., D’Amico, G., Franchis, De, Gatta, R., Tassone, A., Anzaldi, E. J., Barone, M., Bazzini, M., Bianchi, C., Boari, P. I., Bracco, B., Buonauro, C., Buttà, A., Buzzetti, E., Calabria, S., Caradio, F., Carleo, P., Carrabba, Maria, Castorani, D., Cecchetto, L., Cicco, L., Cimini, S., Colombo, C., B. M., Vuono, De, Denegri, S., Del, Corso, Giosia, Di, Donnarumma, P., Giorgini, E., Grassi, P., Grembiale, D., Hijazi, A., Iamele, D., Lorusso, L., Marchese, G., Marra, Alberto, Masala, M., Miceli, M., Montebianco, G., Murgia, A. L., Naccarato, G., Padula, P., Pattoneri, D., Perego, P., Pesce, F., Petramala, P., Piano, L., Pinto, S., Pinna, D., Pignataro, M., Pretti, F. S., Pucci, V., Salinaro, G., Salzano, F., Santarossa, A., Scarpini, C., Scicali, F., Sirico, R., Suppressa, D., Talia, P., Torres, M., Traversa, D., Vazzana, M., Vecchio, Claudia, Vettore, R., Vitale, E., Basili, S., Raparelli, V., Napoleone, L., Talerico, G., Corazza, G.R., Perticone, F., Sacerdoti, D., Andriulli, A., Licata, A., Pietrangelo, A., Picardi, A., Raimondo, G., Violi, F., Palasciano, Giuseppe, D’Alitto, Felicia, Palmieri, Vincenzo Ostilio, Santovito, Daniela, Di Michele, Dario, Croce, Giuseppe, Brocco, Silvia, Fasolato, Silvano, Cecchetto, Lara, Bombonato, Giancarlo, Bertoni, Michele, Restuccia, Tea, Andreozzi, Paola, Liguori, Maria Livia, Caroleo, Benedetto, Perticone, Maria, Staltari, Orietta, Manfredini, Roberto, De Giorgi, Alfredo, Averna, Maurizio, Giammanco, Antonina, Granito, Alessandro, Pettinari, Irene, Marinelli, Sara, Bolondi, Luigi, Falsetti, Lorenzo, Salvi, Aldo, Durante-Mangoni, Emanuele, Cesaro, Flavio, Farinaro, Vincenza, Ragone, Enrico, Morana, Ignazio, Ippolito, Antonio, Iacobellis, Angelo, Niro, Grazia, Merla, Antonio, Maimone, Sergio, Cacciola, Irene, Varvara, Doriana, Drenaggi, Davide, Staffolani, Silvia, Vespasiani-Gentilucci, Umberto, Galati, Giovanni, Gallo, Paolo, Davì, Giovanni, Schiavone, Cosima, Santilli, Francesca, Tana, Claudio, Soresi, Maurizio, Bianchi Giovanni, Battista, Carderi, Isabella, Pinto, Antonio, Tuttolomondo, Antonino, Ferrari, Giovanni, Gresele, Paolo, Fierro, Tiziana, Morelli, Olivia, Laffi, Giacomo, Romanelli, Roberto Giulio, Arena, Umberto, Stasi, Cristina, Gasbarrini, Antonio, Garcovich, Matteo, Zocco, Maria Assunta, Riccardi, Laura, Ainora, Maria Elena, Capeci, William, Martino Giuseppe, Pio, Nobili, Lorenzo, Cavallo, Maurizio, Frugiuele, Pierluigi, Greco, Antonio, Ventura, Paolo, Cuoghi, Chiara, Marcacci, Matteo, Serviddio, Gaetano, Vendemiale, Gianluigi, Villani, Rosanna, Gargano, Ruggiero, Vidili, Gianpaolo, Di Cesare, Valentina, Masala, Maristella, Delitala, Giuseppe, Invernizzi, Pietro, Vincenzo, Ronca, Di Minno, Giovanni, Tufano, Antonella, Purrello, Francesco, Privitera, Graziella, Forgione, Alessandra, Curigliano, Valentina, Senzolo, Marco, Rodríguez-Castro, Kryssia Isabel, Giannelli, Gianluigi, Serra, Carla, Neri, Sergio, Pignataro, Pietro, Rizzetto, Mario, Debernardi, Venon Wilma, Svegliati, Baroni Gianluca, Bergamaschi, Gaetano, Masotti, Michela, Costanzo, Filippo, Antonio, Figliomeni, Angelico, Francesco, Del Ben, Maria, Polimeni, Licia, Proietti, Marco, Cangemi, Roberto, Romiti Giulio, Francesco, Toriello, Filippo, Sperduti, Nicolò, Santangelo, Giuseppe, Visioli, Giacomo, Todisco, Tommaso, Vestri Anna, Rita, Farcomeni, Alessio, Corrao, Salvatore, Gobbi, Paolo, Corradini, Elena, Costantino, Giorgio, Tripepi, Giovanni, Angelico, Mario, D’Amico, Gennaro, De Franchis, Roberto, Gatta, Angelo, Tassone, Eliezer Joseph, Anzaldi, Massimiliano, Barone, Milena, Bazzini, Cristina, Bianchi, Paola Ilaria, Boari, Benedetta, Bracco, Christian, Buonauro, Agostino, Buttà, Carmelo, Buzzetti, Elena, Calabria, Stefano, Caradio, Federica, Carleo, Pietro, Carrabba Maria, Domenica, Castorani, Luigi, Cicco, Sebastiano, Cimini, Claudia, Colombo, Barbara Maria, De Vuono, Stefano, Denegri, Andrea, Del Corso, Lisette, Di Giosia, Paolo, Donnarumma, Emilia, Giorgini, Paolo, Grassi, Davide, Grembiale, Alessandro, Hijazi, Daniel, Iamele, Luigi, Lorusso, Giusi, Marchese, Alessandra, Marra Alberto, Maria, Miceli, Giuseppe, Montebianco, Abenavoli Ludovico, Murgia, Giuseppe, Naccarato, Paola, Padula, Donatella, Pattoneri, Paolo, Perego, Francesca, Pesce, Paola, Petramala, Luigi, Piano, Salvatore, Pinto, Daniela, Pinna, Miriam, Pignataro, Francesca Serena, Pretti, Vincenzo, Pucci, Giacomo, Salinaro, Francesco, Salzano, Andrea, Santarossa, Claudia, Scarpini, Francesca, Scicali, Roberto, Sirico, Domenico, Suppressa, Patrizia, Talia, Michela, Torres, Daniele, Traversa, Matteo, Vazzana, Natale, Vecchio Claudia, Rita, Vettore, Elia, Vitale, Francesco, Basili, S, Raparelli, V, Napoleone, L, Talerico, G, Corazza, G, Perticone, F, Sacerdoti, D, Andriulli, A, Licata, A, Pietrangelo, A, Picardi, A, Raimondo, G, Violi, F, Palasciano, G, D'Alitto, F, Palmieri, V, Santovito, D, Di Michele, D, Croce, G, Brocco, S, Fasolato, S, Cecchetto, L, Bombonato, G, Bertoni, M, Restuccia, T, Andreozzi, P, Liguori, M, Caroleo, B, Perticone, M, Staltari, O, Manfredini, R, De Giorgi, A, Averna, M, Giammanco, A, Granito, A, Pettinari, I, Marinelli, S, Bolondi, L, Falsetti, L, Salvi, A, Durante-Mangoni, E, Cesaro, F, Farinaro, V, Ragone, E, Morana, I, Ippolito, A, Iacobellis, A, Niro, G, Merla, A, Maimone, S, Cacciola, I, Varvara, D, Drenaggi, D, Staffolani, S, Vespasiani-Gentilucci, U, Galati, G, Gallo, P, Davi, G, Schiavone, C, Santilli, F, Tana, C, Soresi, M, Bianchi Giovanni, B, Carderi, I, Pinto, A, Tuttolomondo, A, Ferrari, G, Gresele, P, Fierro, T, Morelli, O, Laffi, G, Romanelli, R, Arena, U, Stasi, C, Gasbarrini, A, Garcovich, M, Zocco, M, Riccardi, L, Ainora, M, Capeci, W, Martino Giuseppe, P, Nobili, L, Cavallo, M, Frugiuele, P, Greco, A, Ventura, P, Cuoghi, C, Marcacci, M, Serviddio, G, Vendemiale, G, Villani, R, Gargano, R, Vidili, G, Di Cesare, V, Masala, M, Delitala, G, Invernizzi, P, Vincenzo, R, Di Minno, G, Tufano, A, Purrello, F, Privitera, G, Forgione, A, Curigliano, V, Senzolo, M, Rodriguez-Castro, K, Giannelli, G, Serra, C, Neri, S, Pignataro, P, Rizzetto, M, Debernardi, V, Svegliati, B, Bergamaschi, G, Masotti, M, Costanzo, F, Antonio, F, Angelico, F, Del Ben, M, Polimeni, L, Proietti, M, Cangemi, R, Romiti, G, Toriello, F, Sperduti, N, Santangelo, G, Visioli, G, Todisco, T, Vestri Anna, R, Farcomeni, A, Corrao, S, Gobbi, P, Corradini, E, Costantino, G, Tripepi, G, Angelico, M, D'Amico, G, De Franchis, R, Gatta, A, Tassone, E, Anzaldi, M, Barone, M, Bazzini, C, Bianchi, P, Boari, B, Bracco, C, Buonauro, A, Butta, C, Buzzetti, E, Calabria, S, Caradio, F, Carleo, P, Carrabba Maria, D, Castorani, L, Cicco, S, Cimini, C, Colombo, B, De Vuono, S, Denegri, A, Del Corso, L, Di Giosia, P, Donnarumma, E, Giorgini, P, Grassi, D, Grembiale, A, Hijazi, D, Iamele, L, Lorusso, G, Marchese, A, Marra, A, Miceli, G, Montebianco, A, Murgia, G, Naccarato, P, Padula, D, Pattoneri, P, Perego, F, Pesce, P, Petramala, L, Piano, S, Pinto, D, Pinna, M, Pignataro, F, Pretti, V, Pucci, G, Salinaro, F, Salzano, A, Santarossa, C, Scarpini, F, Scicali, R, Sirico, D, Suppressa, P, Talia, M, Torres, D, Traversa, M, Vazzana, N, Vecchio Claudia, R, Vettore, E, Vitale, F, S Basili, V Raparelli, L Napoleone, G Talerico, G Corazza, F Perticone, D Sacerdoti, A Andriulli, A Licata, A Pietrangelo, A Picardi, G Raimondo, F Violi, MD on behalf of PRO-LIVER Collaborator, Palasciano Giuseppe, D’Alitto Felicia, Palmieri Vincenzo Ostilio, Santovito Daniela, Di Michele Dario, Croce Giuseppe, Brocco Silvia, Fasolato Silvano, Cecchetto Lara, Bombonato Giancarlo, Bertoni Michele, Restuccia Tea, Andreozzi Paola, Liguori Maria Livia, Caroleo Benedetto, Perticone Maria, Staltari Orietta, Manfredini Roberto, De Giorgi Alfredo, Averna Maurizio, Giammanco Antonina, Granito Alessandro, Pettinari Irene, Marinelli Sara, Bolondi Luigi, Falsetti Lorenzo, Salvi Aldo, Durante-Mangoni Emanuele, Cesaro Flavio, Farinaro Vincenza, Ragone Enrico, Morana Ignazio, Ippolito Antonio, Iacobellis Angelo, Niro Grazia, Merla Antonio, Maimone Sergio, Cacciola Irene, Varvara Doriana, Drenaggi Davide, Staffolani Silvia, Vespasiani-Gentilucci Umberto, Galati Giovanni, Gallo Paolo, Davi Giovanni, Schiavone Cosima, Santilli Francesca, Tana Claudio, Soresi Maurizio, Bianchi Giovanni Battista, Carderi Isabella, Pinto Antonio, Tuttolomondo Antonino, Ferrari Giovanni, Gresele Paolo, Fierro Tiziana, Morelli Olivia, Laffi Giacomo, Romanelli Roberto Giulio, Arena Umberto, Stasi Cristina, Gasbarrini Antonio, Garcovich Matteo, Zocco Maria Assunta, Riccardi Laura, Ainora Maria Elena, Capeci William, Martino Giuseppe Pio, Nobili Lorenzo, Cavallo Maurizio, Frugiuele Pierluigi, Greco Antonio, Ventura Paolo, Cuoghi Chiara, Marcacci Matteo, Serviddio Gaetano, Vendemiale Gianluigi, Villani Rosanna, Gargano Ruggiero, Vidili Gianpaolo, Di Cesare Valentina, Masala Maristella, Delitala Giuseppe, Invernizzi Pietro, Vincenzo Ronca, Di Minno Giovanni, Tufano Antonella, Purrello Francesco, Privitera Graziella, Forgione Alessandra, Curigliano Valentina, Senzolo Marco, Rodríguez-Castro Kryssia Isabel, Giannelli Gianluigi, Serra Carla, Neri Sergio, Pignataro Pietro, Rizzetto Mario, Debernardi Venon Wilma, Svegliati Baroni Gianluca, Bergamaschi Gaetano, Masotti Michela, Costanzo Filippo, Antonio Figliomeni, Angelico Francesco, Del Ben Maria, Polimeni Licia, Proietti Marco, Cangemi Roberto, Romiti Giulio Francesco, Toriello Filippo, Sperduti Nicolò, Santangelo Giuseppe, Visioli Giacomo, Todisco Tommaso, Vestri Anna Rita, Farcomeni Alessio, Corrao Salvatore, Gobbi Paolo, Corradini Elena, Costantino Giorgio, Tripepi Giovanni, Angelico Mario, D’Amico Gennaro, de Franchis Roberto, Gatta Angelo, Tassone Eliezer Joseph, Anzaldi Massimiliano, Barone Milena, Bazzini Cristina, Bianchi Paola Ilaria, Boari Benedetta, Bracco Christian, Buonauro Agostino, Buttà Carmelo, Buzzetti Elena, Calabria Stefano, Caradio Federica, Carleo Pietro, Carrabba Maria Domenica, Castorani Luigi, Cicco Sebastiano, Cimini Claudia, Colombo Barbara Maria, De Vuono Stefano, Denegri Andrea, Del Corso Lisette, Di Giosia Paolo, Donnarumma Emilia, Giorgini Paolo, Grassi Davide, Grembiale Alessandro, Hijazi Daniel, Iamele Luigi, Lorusso Giusi, Marchese Alessandra, Marra Alberto Maria, Miceli Giuseppe, Montebianco Abenavoli Ludovico, Murgia Giuseppe, Naccarato Paola, Padula Donatella, Pattoneri Paolo, Perego Francesca, Pesce Paola, Petramala Luigi, Piano Salvatore, Pinto Daniela, Pinna Miriam, Pignataro Francesca Serena, Pretti Vincenzo, Pucci Giacomo, Salinaro Francesco, Salzano Andrea, Santarossa Claudia, Scarpini Francesca, Scicali Roberto, Sirico Domenico, Suppressa Patrizia, Talia Michela, Torres Daniele, Traversa Matteo, Vazzana Natale, Vecchio Claudia Rita, Vettore Elia, Vitale Francesco, Corazza, G. R., Guidacci, Raimondo, Palasciano, G., D'Alitto, F., Palmieri, V. O., Santovito, D., Di Michele, D., Croce, G., Brocco, S., Fasolato, S., Cecchetto, L., Bombonato, G., Bertoni, M., Restuccia, T., Andreozzi, P., Liguori, M. L., Caroleo, B., Perticone, M., Staltari, O., Manfredini, R., De Giorgi, A., Averna, M., Giammanco, A., Granito, A., Pettinari, I., Marinelli, S., Bolondi, L., Falsetti, L., Salvi, A., Durante-Mangoni, E., Cesaro, F., Farinaro, V., Ragone, E., Morana, I., Ippolito, A., Iacobellis, A., Niro, G., Merla, A., Maimone, S., Cacciola, I., Varvara, D., Drenaggi, D., Staffolani, S., Vespasiani-Gentilucci, U., Galati, G., Gallo, P., Davi, G., Schiavone, C., Santilli, F., Tana, C., Soresi, M., Bianchi Giovanni, B., Carderi, I., Pinto, A., Tuttolomondo, A., Ferrari, G., Gresele, P., Fierro, T., Morelli, O., Laffi, G., Romanelli, R. G., Arena, U., Stasi, C., Gasbarrini, A., Garcovich, M., Zocco, M. A., Riccardi, L., Ainora, M. E., Capeci, W., Martino Giuseppe, P., Nobili, L., Cavallo, M., Frugiuele, P., Greco, A., Ventura, P., Cuoghi, C., Marcacci, M., Serviddio, G., Vendemiale, G., Villani, R., Gargano, R., Vidili, G., Di Cesare, V., Masala, M., Delitala, G., Invernizzi, P., Vincenzo, R., Di Minno, G., Tufano, A., Purrello, F., Privitera, G., Forgione, A., Curigliano, V., Senzolo, M., Rodriguez-Castro, K. I., Giannelli, G., Serra, C., Neri, S., Pignataro, P., Rizzetto, M., Debernardi, V. W., Svegliati, B. G., Bergamaschi, G., Masotti, M., Costanzo, F., Antonio, F., Angelico, F., Del Ben, M., Polimeni, L., Proietti, M., Cangemi, R., Romiti, G. F., Toriello, F., Sperduti, N., Santangelo, G., Visioli, G., Todisco, T., Vestri Anna, R., Farcomeni, A., Corrao, S., Gobbi, P., Corradini, E., Costantino, G., Tripepi, G., Angelico, M., D'Amico, G., De Franchis, R., Gatta, A., Tassone, E. J., Anzaldi, M., Barone, M., Bazzini, C., Bianchi, P. I., Boari, B., Bracco, C., Buonauro, A., Butta, C., Buzzetti, E., Calabria, S., Caradio, F., Carleo, P., Carrabba Maria, D., Castorani, L., Cicco, S., Cimini, C., Colombo, B. M., De Vuono, S., Denegri, A., Del Corso, L., Di Giosia, P., Donnarumma, E., Giorgini, P., Grassi, D., Grembiale, A., Hijazi, D., Iamele, L., Lorusso, G., Marchese, A., Marra, A. M., Miceli, G., Montebianco, A. L., Murgia, G., Naccarato, P., Padula, D., Pattoneri, P., Perego, F., Pesce, P., Petramala, L., Piano, S., Pinto, D., Pinna, M., Pignataro, F. S., Pretti, V., Pucci, G., Salinaro, F., Salzano, A., Santarossa, C., Scarpini, F., Scicali, R., Sirico, D., Suppressa, P., Talia, M., Torres, D., Traversa, M., Vazzana, N., Vecchio Claudia, R., Vettore, E., and Vitale, F.

Subjects
Liver Cirrhosis, Male, Settore MED/09 - Medicina Interna, 030204 cardiovascular system & hematology, Gastroenterology, Severity of Illness Index, cjirrhosis, ACTIVATION, 0302 clinical medicine, Risk Factors, Medicine, Platelet, Prospective Studies, Prospective cohort study, RISK, Aged, 80 and over, medicine.diagnostic_test, PRO-LIVER, Platelet, cirrhosis, gastrointestinal bleeding, ASSOCIATION, Middle Aged, Prognosis, Italy, 030211 gastroenterology & hepatology, Female, Gastrointestinal Hemorrhage, Human, Adult, Platelets, medicine.medical_specialty, Prognosi, Liver Cirrhosi, MEDLINE, COAGULATION, gastrointestinal bleeding, Socio-culturale, Hemorrhage, Hepatology, Follow-Up Studie, 03 medical and health sciences, Text mining, Internal medicine, Severity of illness, ENDOTOXEMIA, Pro-Liver Study, Humans, HEMOSTASIS, International Normalized Ratio, Aged, Proportional Hazards Models, Prothrombin time, Cirrhosi, Platelet Count, Bleeding, Liver Cirrhosis, business.industry, Proportional hazards model, Platelet Count, Risk Factor, cirrhosis, bleeding, Thrombocytopenia, Prospective Studie, THROMBOSIS, Platelets, cjirrhosis, bleeding, PRO-LIVER, Proportional Hazards Model, Prothrombin Time, business, DECOMPENSATED CIRRHOSIS, Follow-Up Studies
Abstract

OBJECTIVES: Thrombocytopenia is a hallmark for patients with cirrhosis and it is perceived as a risk factor for bleeding events. However, the relationship between platelet count and bleeding is still unclear. METHODS: We investigated the relationship between platelet count and major or clinical relevant nonmajor bleedings during a follow-up of ∼4 years. RESULTS: A total of 280 cirrhotic patients with different degrees of liver disease (67% males; age 64±37 years; 47% Child–Pugh B and C) were followed up for a median of 1,129 (interquartile range: 800–1,498) days yielding 953.12 patient-year of observation. The annual rate of any significant bleeding was 5.45%/year (3.57%/year and 1.89%/year for major and minor bleeding, respectively). Fifty-two (18.6%) patients experienced a major (n=34) or minor (n=18) bleeding event, predominantly from gastrointestinal origin. Platelet counts progressively decreased with the worsening of liver disease and were similar in patients with or without major or minor bleeding: a platelet count ≤50×103/μl was detected in 3 (6%) patients with and in 20 (9%) patients without any bleeding event. Conversely, prothrombin time-international normalized ratio was slightly higher in patients with overall or major bleeding. On Cox proportional hazard analysis, only a previous gastrointestinal bleeding (hazard ratio (HR): 1.96; 95% confidence interval: 1.11–3.47; P=0.020) and encephalopathy (HR: 2.05; 95% confidence interval: 1.16–3.62; P=0.013) independently predicted overall bleeding events. CONCLUSIONS: Platelet count does not predict unprovoked major or minor bleeding in cirrhotic patients.

Published
2018

8. Pharmacophore Hybridization To Discover Novel Topoisomerase II Poisons with Promising Antiproliferative Activity

Author

Marco De Vivo, Jose M. Arencibia, Anna Minarini, Elirosa Minniti, Laura Riccardi, José-Antonio Ortega, Maria Laura Greco, Marco Borgogno, Claudia Sissi, Ortega, Jose Antonio, Riccardi, Laura, Minniti, Elirosa, Borgogno, Marco, Arencibia, Jose M, Greco, Maria L, Minarini, Anna, Sissi, Claudia, and De Vivo, Marco

Subjects
0301 basic medicine, Protein Conformation, Computational biology, Pharmacology, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Cell Line, Tumor, Drug Discovery, medicine, Quinazoline, Humans, Topoisomerase II Inhibitors, Etoposide, Cell Proliferation, biology, 010405 organic chemistry, Chemistry, Topoisomerase, Topoisomerase type II, Poisons, quinazoline, anticancer, Anticancer drug, 0104 chemical sciences, Molecular Docking Simulation, DNA Topoisomerases, Type II, 030104 developmental biology, Drug Design, ddc:540, biology.protein, Molecular Medicine, Pharmacophore, Medical science, Type II topoisomerase, Human cancer, medicine.drug
Abstract

We used a pharmacophore hybridization strategy to combine key structural elements of merbarone and etoposide and generated new type II topoisomerase (topoII) poisons. This first set of hybrid topoII poisons shows promising antiproliferative activity on human cancer cells, endorsing their further exploration for anticancer drug discovery.

Published
2017

9. Incidence and Recurrence of Portal Vein Thrombosis in Cirrhotic Patients

Author

Violi, F., Corazza, G. R., Caldwell, S. H., Talerico, G., Romiti, G. F., Napoleone, L., Perticone, F., Bolondi, L., Pietrangelo, A., Vestri, A. R., Raparelli, V., Basili, S., Elena, A. M., Paola, A., Angelo, A., Bottino, Francesco, Mario, A., Antonio, F., Massimiliano, A., Umberto, A., Maurizio, A., Milena, B., Cristina, B., Gaetano, B., Michele, B., Battista, B. G., Ilaria, B. P., Benedetta, B., Giancarlo, B., Christian, B., Silvia, B., Agostino, B., Carmelo, B., Buzzetti, E., Irene, C., Stefano, C., Roberto, C., William, C., Santagati, Federica, Isabella, C., Pietro, C., Benedetto, C., Domenica, C. M., Luigi, C., Maurizio, C., Lara, C., Flavio, C., Sebastiano, C., Claudia, C., Maria, C. B., Elena, C., Amato, Salvatore, Giorgio, C., Filippo, C., Giuseppe, C., Chiara, C., Valentina, C., Felicia, D., Gennaro, D., Roberto, D. F., Alfredo, D. G., Stefano, D. V., Wilma, D. V., Maria, D. B., Lisette, D. C., Giuseppe, D., Andrea, D., Valentina, D. C., Paolo, D. G., Dario, D. M., Giovanni, D. M., Emilia, D., Davide, D., Emanuele, D. -M., Falsetti, L., Alessio, F., Vincenza, F., Silvano, F., Giovanni, F., Tiziana, F., Alessandra, F., Pierluigi, F., Giovanni, G., Vigneri, Paolo, Matteo, G., Ruggiero, G., Antonio, G., Angelo, G., Antonina, G., Gianluigi, G., Alessandro, G., Davide, G., Daniel, H., Angelo, I., Luigi, I., Pietro, I., Antonio, I., Giacomo, L., Anna, L., Livia, L. M., Giusi, L., Sergio, M., Roberto, M., Matteo, M., Alessandra, M., Sara, M., Maria, M. A., Pio, M. G., Maristella, M., Michela, M., Antonio, M., Giuseppe, M., Ludovico, M. A., Ignazio, M., Olivia, M., Paola, N., Sergio, N., Grazia, N., Lorenzo, N., Donatella, P., Giuseppe, P., Ostilio, P. V., Daniele, P., Francesca, P., Maria, P., Paola, P., Luigi, P., Irene, P., Salvatore, P., Antonio, P., Serena, P. F., Pietro, P., Pasquale, P., Miriam, P., Daniela, P., Licia, P., Vincenzo, P., Graziella, P., Giacomo, P., Francesco, P., Enrico, R., Giovanni, R., Tea, R., Laura, R., Mario, R., Isabel, R. -C. K., Giulio, R. R., Eleonora, R., David, S., Francesco, S., Aldo, S., Andrea, S., Giuseppe, S., Claudia, S., Francesca, S., Daniela, S., Cosima, S., Roberto, S., Marco, S., Carla, S., Gaetano, S., Domenico, S., Maurizio, S., Nicolo, S., Silvia, S., Orietta, S., Stasi, C., Patrizia, S., Gianluca, S. B., Michela, T., Claudio, T., Joseph, T. E., Tommaso, T., Filippo, T., Daniele, T., Matteo, T., Giovanni, T., Antonella, T., Antonino, T., Doriana, V., Natale, V., Rita, V. C., Gianluigi, V., Paolo, V., Umberto, V. -G., Elia, V., Gianpaolo, V., Villani, R., Ronca, V., Giacomo, V., Francesco, V., Assunta, Z. M., Paolo, P., Marco, P., and Francesco Violi, Gino Roberto Corazza, Stephen H. Caldwell, Giovanni Talerico, Giulio Francesco Romiti, Laura Napoleone, Francesco Perticone, Luigi Bolondi, Antonello Pietrangelo, Anna Rita Vestri, Valeria Raparelli, Stefania Basili, Ainora Maria Elena, Andreozzi Paola, AndriulliAngelo,Angelico Francesco, Angelico Mario, Figliomeni Antonio, Anzaldi Massimiliano, Arena Umberto, Averna Maurizio, Barone Milena, Bazzini Cristina, Bergamaschi Gaetano, Bertoni Michele, Bianchi, Giovanni Battista, Bianchi Paola Ilaria, Boari Benedetta, Bombonato Giancarlo, Bracco Christian, Brocco Silvia, Buonauro, Agostino, Buttà Carmelo, Buzzetti Elena, Cacciola Irene, Calabria Stefano, Cangemi Roberto, Capeci William, Caradio, Federica, Carderi Isabella, Carleo Pietro, Caroleo Benedetto, Carrabba Maria Domenica, Castorani Luigi, Cavallo Maurizio, Cecchetto Lara, Cesaro Flavio, Cicco Sebastiano, Cimini Claudia, Colombo Barbara Maria, Corradini Elena, Corrao Salvatore, Costantino Giorgio, Costanzo Filippo, Croce Giuseppe, Cuoghi Chiara, Curigliano Valentina, D’Alitto Felicia, D’Amico Gennaro, De Franchis Roberto, De Giorgi Alfredo, De Vuono Stefano, Debernardi Venon Wilma, Del Ben Maria, Del Corso Lisette, Delitala Giuseppe, Denegri Andrea, Di Cesare Valentina, Di Giosia Paolo, Di Michele Dario, Di Minno Giovanni, Donnarumma Emilia, Drenaggi Davide, Durante-Mangoni Emanuele, Falsetti Lorenzo, FarcomeniAlessio, FarinaroVincenza, Fasolato Silvano, Ferrari Giovanni, Fierro Tiziana, Forgione Alessandra, Frugiuele Pierluigi, Galati Giovanni, Gallo Paolo, Garcovich Matteo, Gargano Ruggiero, Gasbarrini Antonio, Gatta Angelo, Giammanco Antonina, Giannelli Gianluigi, Giorgini Paolo, Gobbi Paolo, Granito Alessandro, GrassiDavide, Greco Antonio, Grembiale Alessandro, Gresele Paolo, Hijazi Daniel, Iacobellis, Angelo, Iamele Luigi, Invernizzi Pietro, Ippolito Antonio, Laffi, Giacomo, Licata Anna, Liguori Maria Livia, Lorusso Giusi, Maimone Sergio, Manfredini Roberto, Marcacci Matteo, Marchese Alessandra, Marinelli Sara, Marra Alberto Maria, Martino Giuseppe Pio, Masala Maristella, Masotti Michela, Merla Antonio, Miceli Giuseppe, Montebianco Abenavoli Ludovico, Morana Ignazio, Morelli Olivia, Murgia Giuseppe, Naccarato Paola, Neri Sergio, Niro Grazia, Nobili Lorenzo, Padula Donatella, PalascianoGiuseppe, PalmieriVincenzoOstilio, PastoriDaniele, Pattoneri Paolo, Perego Francesca, Perticone Maria, Pesce Paola, Petramala Luigi, Pettinari Irene, Piano Salvatore, Picardi Antonio, Pignataro Francesca Serena, Pignataro Pietro, Pignatelli Pasquale, PinnaMiriam, Pinto Antonio, Pinto Daniela, Polimeni Licia, Pretti Vincenzo, Privitera Graziella, Proietti Marco, Pucci Giacomo, Purrello Francesco, Ragone Enrico, Raimondo Giovanni, Restuccia Tea, Riccardi Laura, RizzettoMario, Rodríguez- Castro Kryssia Isabel, Romanelli Roberto Giulio, Ruscio Eleonora, Sacerdoti David, Salinaro Francesco, Salvi Aldo, Salzano Andrea, SantangeloGiuseppe, Santarossa Claudia, Santilli Francesca, Santovito Daniela, Scarpini Francesca, Schiavone Cosima, Scicali Roberto, SenzoloMarco, Serra Carla, Serviddio Gaetano, Sirico Domenico, Soresi Maurizio, Sperduti Nicolò, Staffolani Silvia, Staltari Orietta, Stasi Cristina, Suppressa Patrizia, Svegliati Baroni Gianluca, Talia Michela, Tana Claudio, Tassone Eliezer Joseph, Todisco Tommaso, Toriello Filippo, Torres Daniele, Traversa Matteo, Tripepi Giovanni, Tufano Antonella, Tuttolomondo Antonino, Varvara Doriana, Vazzana Natale, Vecchio Claudia Rita, Vendemiale Gianluigi, Ventura Paolo, Vespasiani-Gentilucci Umberto, Vettore Elia, Vidili Gianpaolo, Villani Rosanna, Vincenzo Ronca, Visioli Giacomo, Vitale Francesco, Zocco Maria Assunta.

Subjects
Liver Cirrhosis, Male, medicine.medical_specialty, Letter to the editor, Time Factors, MEDLINE, Portal Vein Thrombosis Cirrhotic Patients, outcomes, NO, coagulopathy, Recurrence, Risk Factors, Medicine, Humans, Aged, Female, Incidence, Italy, Middle Aged, Prospective Studies, Registries, Ultrasonography, Doppler, Venous Thrombosis, Portal Vein, portal vein thrombosis, Prospective cohort study, risk-factors, liver-transplantation, mortality, Ultrasonography, business.industry, Incidence (epidemiology), portal vein thrombosis, liver-transplantation, risk-factors, coagulopathy, mortality, outcomes, Doppler, Hematology, medicine.disease, Portal vein thrombosis, Radiology, business
Abstract

Cirrhosis has been long considered a risk factor for bleeding due to the co-existence of the so-called ‘coagulopathy’. More recently, however, compelling evidences have been provided on the occurrence of thrombotic events in the portal and systemic circulation.3–5 Portal vein thrombosis (PVT) is predominantly observed in patients with moderate to severe liver failure with a variable prevalence ranging from 0.6 to 25%. Only fewstudies have provided a longitudinal assessment of the PVT incidence and its sequelae, including recurrence and survival.9–14 Due to the variability of PVT incidence and the paucity of data regarding recurrence and survival,15–20 we prospectively analysed the incidence and the recurrence of PVT in the population of Portal vein thrombosis Relevance On Liver cirrhosis: ItalianVenous thromboticEventsRegistry (PROLIVER), a multi-centre study,8 which involved 43 enrolling centres in Italy (ClinicalTrials.gov Identifier: NCT01470547).

Published
2019

10. Novel xanthone-polyamine conjugates as catalytic inhibitors of human topoisomerase IIα

Author

Neil Osheroff, Jo Ann W. Byl, Elirosa Minniti, Anna Minarini, Michela Rosini, Marco De Vivo, Laura Riccardi, Claudia Sissi, Minniti, Elirosa, Byl, Jo Ann W., Riccardi, Laura, Sissi, Claudia, Rosini, Michela, De Vivo, Marco, Minarini, Anna, and Osheroff, Neil

Subjects
0301 basic medicine, Polyamine, ATPase, Clinical Biochemistry, Pharmaceutical Science, Biochemistry, chemistry.chemical_compound, Adenosine Triphosphate, ATP hydrolysis, Catalytic Domain, Drug Discovery, Xanthone, Polyamines, Topoisomerase II Inhibitors, chemistry.chemical_classification, DNA cleavage, biology, DNA topoisomerase IIα, DNA-Binding Proteins, Molecular Docking Simulation, Molecular Medicine, DNA topoisomerase II, Stereochemistry, Xanthones, Antineoplastic Agents, Type II, Catalytic inhibitor, Article, Catalysis, 03 medical and health sciences, Antigens, Neoplasm, Humans, Antigens, Binding site, Molecular Biology, Binding Sites, Drug Discovery3003 Pharmaceutical Science, Topoisomerase, Organic Chemistry, DNA, Anticancer drug, DNA Topoisomerases, Type II, 030104 developmental biology, Enzyme, chemistry, Xanthone derivative, biology.protein, Neoplasm, Nucleic Acid Conformation, DNA Cleavage, 3003, Topoisomerase-II Inhibitor, DNA Topoisomerases
Abstract

It has been proposed that xanthone derivatives with anticancer potential act as topoisomerase II inhibitors because they interfere with the ability of the enzyme to bind its ATP cofactor. In order to further characterize xanthone mechanism and generate compounds with potential as anticancer drugs, we synthesized a series of derivatives in which position 3 was substituted with different polyamine chains. As determined by DNA relaxation and decatenation assays, the resulting compounds are potent topoisomerase IIα inhibitors. Although xanthone derivatives inhibit topoisomerase IIα-catalyzed ATP hydrolysis, mechanistic studies indicate that they do not act at the ATPase site. Rather, they appear to function by blocking the ability of DNA to stimulate ATP hydrolysis. On the basis of activity, competition, and modeling studies, we propose that xanthones interact with the DNA cleavage/ligation active site of topoisomerase IIα and inhibit the catalytic activity of the enzyme by interfering with the DNA strand passage step.

Published
2017

11. Pharmacogenetics and Treatment Response in Narcolepsy Type 1: Relevance of the Polymorphisms of the Drug Transporter Gene ABCB1

Author

Corrado Zenesini, Susi Pelotti, Monica Moresco, Giuseppe Plazzi, Laura Natalia Riccardi, Leonardo Caporali, Fabio Pizza, Moresco, Monica, Riccardi, LAURA NATALIA, Pizza, Fabio, Zenesini, Corrado, Caporali, Leonardo, Plazzi, Giuseppe, and Pelotti, Susi

Subjects
0301 basic medicine, Oncology, Adult, Male, medicine.medical_specialty, Pharmacology (medical), Pharmacology, Neurology (clinical), ATP Binding Cassette Transporter, Subfamily B, Cataplexy, Genotype, Venlafaxine Hydrochloride, DNA Mutational Analysis, Venlafaxine, Modafinil, Polymorphism, Single Nucleotide, Severity of Illness Index, Efficacy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, mental disorders, medicine, Humans, Drug transmembrane transport, Benzhydryl Compounds, Narcolepsy, Cytochrome P-450 CYP3A Inducers, Middle Aged, medicine.disease, 030104 developmental biology, Pharmacogenetics, Antidepressive Agents, Second-Generation, Female, medicine.symptom, Psychology, 030217 neurology & neurosurgery, medicine.drug
Abstract

Objective Narcolepsy type 1 (NT1) is a chronic hypersomnia clinically characterized by daytime sleepiness and cataplexy. Narcolepsy type 1 treatments target individual symptoms: wake-promoting agents (eg, modafinil) are effective for sleepiness, antidepressants (eg, venlafaxine) on cataplexy, whereas sodium oxybate on both. Narcolepsy type 1 patients variably respond to modafinil and venlafaxine independently of individual clinical features. Objective Given the potential influence of drug transmembrane transport (glycoprotein-P) on drug response, we explored the relation between genetic polymorphisms in the ABCB1 gene and clinical response to modafinil/venlafaxine in NT1. Methods Individual drug response and genotypes were assessed in 107 NT1 patients (males/females, 64/43; mean age, 38 ± 21 years) treated with modafinil and/or venlafaxine at stable doses for at least 3 months. Minisequencing was performed to detect single-nucleotide polymorphisms in ABCB1. Patients with different responses to treatment were contrasted by Fisher exact test and multivariate analysis. Results The ABCB1 diplotype was significantly associated with clinical response to modafinil, with the CGC-TTT (1236/2677/3435) being more frequent in the modafinil responder versus nonresponder group (P = 0.013). Conversely, no significant associations with clinical response to venlafaxine were found. Conclusions The ABCB1 variants modulate therapeutic response to modafinil and may partly explain pharmacoresistance in NT1 patients.

Published
2016

12. CYP2B6 gene single-nucleotide polymorphisms in an Italian population sample and relationship with nicotine dependence

Author

Francesco Carano, Gianmarco Ferri, Laura Natalia Riccardi, Stefania Ceccardi, Carla Bini, Susi Pelotti, Riccardi, Laura Natalia, Carano, Francesco, Bini, Carla, Ceccardi, Stefania, Ferri, Gianmarco, and Pelotti, Susi

Subjects
Fagerstrom Test for Nicotine Dependence, Sampling Studie, CYP2B6, Genotype, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Sampling Studies, Nicotine, Gene Frequency, Surveys and Questionnaires, medicine, Humans, Surveys and Questionnaire, Genetic Predisposition to Disease, Allele, Allele frequency, Alleles, Biotransformation, Genetics (clinical), Genetics, Medicine (all), General Medicine, Tobacco Use Disorder, Genotype frequency, Cytochrome P-450 CYP2B6, Italy, medicine.drug, Human
Abstract

The extensively polymorphic CYP2B6 gene metabolizes endogenous and exogenous compounds, among which are nicotine and bupropion, although its contribution to the systemic metabolism of nicotine still remains controversial. In the present study, the distribution of the CYP2B6 variant and genotype frequencies were analyzed in a sample of 202 Italian individuals who were also invited to answer the Fagerström test for nicotine dependence (FTND), in an effort to assess the involvement of CYP2B6 polymorphisms in nicotine dependence. Eight single-nucleotide polymorphisms of CYP2B6 were tested and seven different variants were identified showing frequencies similar to the European population. The reduced activity of the CYP2B6*6 variant was significantly (p=0.025) distributed among the nicotine-dependent individuals compared to non-nicotine dependents. Also, the CYP2B6*1/*6 genotype achieved statistical significance (p=0.016) within the nicotine-dependent individuals. The high occurrence of CYP2B6*6 carriers among nicotine-dependent individuals may suggest a possible involvement in nicotine dependence, with a potential impact on smoking cessation treatments tailored to the individual smoker's genotype.

Published
2015

13. Expanding X-chromosomal forensic haplotype frequencies database: Italian population data of four linkage groups

Author

Donata Luiselli, Stefania Sarno, Carla Bini, Susi Pelotti, Laura Natalia Riccardi, Francesco Carano, Stefania Ceccardi, Bini, Carla, Riccardi, Laura Natalia, Ceccardi, Stefania, Carano, Francesco, Sarno, Stefania, Luiselli, Donata, and Pelotti, Susi

Subjects
Forensic Genetics, Genetic Linkage, X-12, Haplotype frequencie, STR marker, Str markers, Sample (statistics), Investigator, Biology, computer.software_genre, Forensic Genetic, Pathology and Forensic Medicine, Modal haplotype, Genetic, Genetic linkage, Databases, Genetic, Haplotype, Genetics, Kinship, Humans, X-chromosome, Linkage (software), Chromosomes, Human, X, Database, Medicine (all), Forensic science, Haplotypes, Italy, Microsatellite Repeat, Argu, Kinship analysi, computer, Human, Microsatellite Repeats
Abstract

Requests for solving complex kinship casework involving at least one female are increasing and in these circumstances the analysis of X-chromosomal STR markers plays a relevant role. Actually, it is well known the superior statistical power of X-STRs compared to autosomal markers in solving relationship when two sisters or half-sisters are involved and none of parents is available, in maternity testing or in cases involving close relatives as alternative putative fathers. In addition, the possibility to amplify more loci simultaneously and the strategy based on the analysis of four linkage groups to obtain the X-haplotype provide a powerful and validated tool. Nevertheless, haplotypes frequency distribution in different populations is still needed for calculation of probabilities in relationship testing. Published haplotype frequencies from German population data are available, but in different caseworks we found unreported X-haplotypes. To enlarge the forensic X-chromosome database, we present haplotype frequencies and other parameter of forensic interest obtained from 200 anonymous DNA samples of unrelated Italian males for the four linkage groups included in the Investigator Argus X-12 kit. From the comparison of the Italian sample haplotype frequencies with other populations, significant genetic distances were found with Asian and African populations, but not with Europeans. Finally, casework examples of complex kinship analysis are presented.

Published
2014

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