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2. A novel likely pathogenetic variant p.(Cys235Arg) of the MEN1 gene in multiple endocrine neoplasia type 1 with multifocal glucagonomas

Author

Pathologie Pathologen staf, Cancer, Smirne, C, Giacomini, G M, Berton, A M, Pasini, B, Mercalli, F, Prodam, F, Caputo, M, Brosens, L A A, Mollero, E L M, Pitino, R, Pirisi, M, Aimaretti, G, Ghigo, E, Pathologie Pathologen staf, Cancer, Smirne, C, Giacomini, G M, Berton, A M, Pasini, B, Mercalli, F, Prodam, F, Caputo, M, Brosens, L A A, Mollero, E L M, Pitino, R, Pirisi, M, Aimaretti, G, and Ghigo, E

Published
2024

3. A novel likely pathogenetic variant p.(Cys235Arg) of the MEN1gene in multiple endocrine neoplasia type 1 with multifocal glucagonomas

Author

Smirne, C., Giacomini, G. M., Berton, A. M., Pasini, B., Mercalli, F., Prodam, F., Caputo, M., Brosens, L. A. A., Mollero, E. L. M., Pitino, R., Pirisi, M., Aimaretti, G., and Ghigo, E.

Abstract

Purpose: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary endocrine syndrome caused by pathogenic variants in MEN1tumor suppressor gene. Diagnosis is commonly based on clinical criteria and confirmed by genetic testing. The objective of the present study was to report on a MEN1 case characterized by multiple pancreatic glucagonomas, with particular concern on the possible predisposing genetic defects. Methods: While conducting an extensive review of the most recent scientific evidence on the unusual glucagonoma familial forms, we analyzed the MEN1gene in a 35-year-old female with MEN1, as well as her son and daughter, using Sanger and next-generation sequencing (NGS) approaches. We additionally explored the functional and structural consequences of the identified variant using in silico analyses. Results: NGS did not show any known pathogenic variant in the tested regions. However, a new non-conservative variant in exon 4 of MEN1gene was found in heterozygosity in the patient and in her daughter, resulting in an amino acid substitution from hydrophobic cysteine to hydrophilic arginine at c.703T > C, p.(Cys235Arg). This variant is absent from populations databases and was never reported in full papers: its characteristics, together with the high specificity of the patient’s clinical phenotype, pointed toward a possible causative role. Conclusion: Our findings confirm the need for careful genetic analysis of patients with MEN1 and establish a likely pathogenic role for the new p.(Cys235Arg) variant, at least in the rare subset of MEN1 associated with glucagonomas.

Published
2024
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4. Pegylated interferon α plus ribavirin for the treatment of chronic hepatitis C: A multicentre independent study supported by the Italian Drug Agency

Author

Mascolo, M.C., Cursaro, C., Scuteri, A., Ranieri, J., Monti, M., Bellentani, S., Gasbarrini, A., Pompili, M., Puoti, C., Bellis, L., Regazzetti, A., Maffezzini, E., Pietrangelo, A., Abbati, G., Raimondo, G., Scribano, L., Martines, D., Baroni, G. Svegliati, Faraci, G., Schianchi, S., Fornaciari, G., Fabris, P., Madonia, S., Civitavecchia, G., Pirisi, M., Smirne, C., Borghi, A., Sardini, C., Andreoletti, M., Morisco, F., Caporaso, N., Fargion, S., Fatta, E., Masutti, F., Bonaventura, M.E., Autolitano, A., Russello, M., Bellia, A., Toniutto, P., Bitetto, D., Mecenate, F., Pasulo, L., Lucà, M.G., Picardi, A., Vespasiani, U., Grattagliano, I., Palasciano, G., Romagno, D., Crespi, C., Gianstefani, A., Gobbo, G., Monti, V., Giannelli, G., Napoli, N., Nosotti, Raspanti, A., Cuccorese, Colombo, A.E., Floridia, Plattella, M.S., Cassano, P., Gentile, I., Blanc, P.L., Messina, V., Bonfante, S., Bellissima, P., Toti, M., Vecchiet, J., Falasca, K., Portelli, V., De Stefano, G., Pietromatera, G., Viganò, P., Re, T., Andreoni, M., Raineri, G., Massari, M., Grossi, P.A., Caputo, S., Cassola, G., Feasi, M., Foti, G., Kunkar, A., Corti, G., Baragli, F., Caterini, L., Migliorini, D., Chiodera, A., Calleri, G., Spezia, C., Baiguera, C., Puoti, M., Brancaccio, G., Gaeta, G.B., Vento, S., Di Biagio, A., Nicolini, L., Liberti, A., Iannece, M.D., Contini, C., Tacconi, D., Caremani, M., Almi, P., Chimenti, M., Cosco, Messeri, D., Esperti, F.C., Paffetti, A., Mastropietro, C., Moretti, A., Spagnolo, A.L., Lomonaco, L., Calì, A., Mandelli, G., Spinzi, G.C., Framarin, L., Berrutti, M., Boccia, S., Simone, L., Pazzi, P., Fornari, F., Comparato, G., Casetti, T., Foschi, F.G., Bertin, T., Salvagnini, M., Samori, A., Ferretti, E., Casiraghi, M.A., Marin, R., Ciancio, A., Campo, N., Testa, R., Rocco, A., Federico, A., Loguercio, C., Rizzo, S., Giannini, E.G., Corbo, M., Riegler, G., Esposito, P., Ricci, G.L., Rosina, Floriano, Tosti, Maria Elena, Borghesio, Elisabetta, Masocco, Maria, Mele, Alfonso, Coppola, Carmine, Milella, Michele, Borgia, Guglielmo, Andreone, Pietro, Koch, Maurizio, Zignego, Anna Linda, Romano, Mario, Carrara, Maurizio, Almasio, Piero Luigi, Azzola, Emilio, Nardone, Gerardo, Benedetti, Antonio, Carosi, Giampiero, Mazzotta, Francesco, Sagnelli, Evangelista, and Rizzetto, Mario

Published
2014
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5. Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

Author

Bellan, M, Patti, G, Hayden, E, Azzolina, D, Pirisi, M, Acquaviva, A, Aimaretti, G, Aluffi Valletti, P, Angilletta, R, Arioli, R, Avanzi, G, Avino, G, Balbo, P, Baldon, G, Baorda, F, Barbero, E, Baricich, A, Barini, M, Barone-Adesi, F, Battistini, S, Beltrame, M, Bertoli, M, Bertolin, S, Bertolotti, M, Betti, M, Bobbio, F, Boffano, P, Boglione, L, Borre, S, Brucoli, M, Calzaducca, E, Cammarata, E, Cantaluppi, V, Cantello, R, Capponi, A, Carriero, A, Casciaro, F, Castello, L, Ceruti, F, Chichino, G, Chirico, E, Cisari, C, Cittone, M, Colombo, C, Comi, C, Croce, E, Daffara, T, Danna, P, Della Corte, F, De Vecchi, S, Dianzani, U, Di Benedetto, D, Esposto, E, Faggiano, F, Falaschi, Z, Ferrante, D, Ferrero, A, Gagliardi, I, Gaidano, G, Galbiati, A, Gallo, S, Garavelli, P, Gardino, C, Garzaro, M, Gastaldello, M, Gavelli, F, Gennari, A, Giacomini, G, Giacone, I, Giai Via, V, Giolitti, F, Gironi, L, Gramaglia, C, Grisafi, L, Inserra, I, Invernizzi, M, Krengli, M, Labella, E, Landi, I, Landi, R, Leone, I, Lio, V, Lorenzini, L, Maconi, A, Malerba, M, Manfredi, G, Martelli, M, Marzari, L, Marzullo, P, Mennuni, M, Montabone, C, Morosini, U, Mussa, M, Nerici, I, Nuzzo, A, Olivieri, C, Padelli, S, Panella, M, Parisini, A, Pasche, A, Pau, A, Pedrinelli, A, Percivale, I, Re, R, Rigamonti, C, Rizzi, E, Rognoni, A, Roveta, A, Salamina, L, Santagostino, M, Saraceno, M, Savoia, P, Sciarra, M, Schimmenti, A, Scotti, L, Spinoni, E, Smirne, C, Tarantino, V, Tillio, P, Vaschetto, R, Vassia, V, Zagaria, D, Zavattaro, E, Zeppegno, P, Zottarelli, F, Sainaghi, P, Bellan M., Patti G., Hayden E., Azzolina D., Pirisi M., Acquaviva A., Aimaretti G., Aluffi Valletti P., Angilletta R., Arioli R., Avanzi G. C., Avino G., Balbo P. E., Baldon G., Baorda F., Barbero E., Baricich A., Barini M., Barone-Adesi F., Battistini S., Beltrame M., Bertoli M., Bertolin S., Bertolotti M., Betti M., Bobbio F., Boffano P., Boglione L., Borre S., Brucoli M., Calzaducca E., Cammarata E., Cantaluppi V., Cantello R., Capponi A., Carriero A., Casciaro F. G., Castello L. M., Ceruti F., Chichino G., Chirico E., Cisari C., Cittone M. G., Colombo C., Comi C., Croce E., Daffara T., Danna P., Della Corte F., De Vecchi S., Dianzani U., Di Benedetto D., Esposto E., Faggiano F., Falaschi Z., Ferrante D., Ferrero A., Gagliardi I., Gaidano G., Galbiati A., Gallo S., Garavelli P. L., Gardino C. A., Garzaro M., Gastaldello M. L., Gavelli F., Gennari A., Giacomini G. M., Giacone I., Giai Via V., Giolitti F., Gironi L. C., Gramaglia C., Grisafi L., Inserra I., Invernizzi M., Krengli M., Labella E., Landi I. C., Landi R., Leone I., Lio V., Lorenzini L., Maconi A., Malerba M., Manfredi G. F., Martelli M., Marzari L., Marzullo P., Mennuni M., Montabone C., Morosini U., Mussa M., Nerici I., Nuzzo A., Olivieri C., Padelli S. A., Panella M., Parisini A., Pasche A., Pau A., Pedrinelli A. R., Percivale I., Re R., Rigamonti C., Rizzi E., Rognoni A., Roveta A., Salamina L., Santagostino M., Saraceno M., Savoia P., Sciarra M., Schimmenti A., Scotti L., Spinoni E., Smirne C., Tarantino V., Tillio P. A., Vaschetto R., Vassia V., Zagaria D., Zavattaro E., Zeppegno P., Zottarelli F., Sainaghi P. P., Bellan, M, Patti, G, Hayden, E, Azzolina, D, Pirisi, M, Acquaviva, A, Aimaretti, G, Aluffi Valletti, P, Angilletta, R, Arioli, R, Avanzi, G, Avino, G, Balbo, P, Baldon, G, Baorda, F, Barbero, E, Baricich, A, Barini, M, Barone-Adesi, F, Battistini, S, Beltrame, M, Bertoli, M, Bertolin, S, Bertolotti, M, Betti, M, Bobbio, F, Boffano, P, Boglione, L, Borre, S, Brucoli, M, Calzaducca, E, Cammarata, E, Cantaluppi, V, Cantello, R, Capponi, A, Carriero, A, Casciaro, F, Castello, L, Ceruti, F, Chichino, G, Chirico, E, Cisari, C, Cittone, M, Colombo, C, Comi, C, Croce, E, Daffara, T, Danna, P, Della Corte, F, De Vecchi, S, Dianzani, U, Di Benedetto, D, Esposto, E, Faggiano, F, Falaschi, Z, Ferrante, D, Ferrero, A, Gagliardi, I, Gaidano, G, Galbiati, A, Gallo, S, Garavelli, P, Gardino, C, Garzaro, M, Gastaldello, M, Gavelli, F, Gennari, A, Giacomini, G, Giacone, I, Giai Via, V, Giolitti, F, Gironi, L, Gramaglia, C, Grisafi, L, Inserra, I, Invernizzi, M, Krengli, M, Labella, E, Landi, I, Landi, R, Leone, I, Lio, V, Lorenzini, L, Maconi, A, Malerba, M, Manfredi, G, Martelli, M, Marzari, L, Marzullo, P, Mennuni, M, Montabone, C, Morosini, U, Mussa, M, Nerici, I, Nuzzo, A, Olivieri, C, Padelli, S, Panella, M, Parisini, A, Pasche, A, Pau, A, Pedrinelli, A, Percivale, I, Re, R, Rigamonti, C, Rizzi, E, Rognoni, A, Roveta, A, Salamina, L, Santagostino, M, Saraceno, M, Savoia, P, Sciarra, M, Schimmenti, A, Scotti, L, Spinoni, E, Smirne, C, Tarantino, V, Tillio, P, Vaschetto, R, Vassia, V, Zagaria, D, Zavattaro, E, Zeppegno, P, Zottarelli, F, Sainaghi, P, Bellan M., Patti G., Hayden E., Azzolina D., Pirisi M., Acquaviva A., Aimaretti G., Aluffi Valletti P., Angilletta R., Arioli R., Avanzi G. C., Avino G., Balbo P. E., Baldon G., Baorda F., Barbero E., Baricich A., Barini M., Barone-Adesi F., Battistini S., Beltrame M., Bertoli M., Bertolin S., Bertolotti M., Betti M., Bobbio F., Boffano P., Boglione L., Borre S., Brucoli M., Calzaducca E., Cammarata E., Cantaluppi V., Cantello R., Capponi A., Carriero A., Casciaro F. G., Castello L. M., Ceruti F., Chichino G., Chirico E., Cisari C., Cittone M. G., Colombo C., Comi C., Croce E., Daffara T., Danna P., Della Corte F., De Vecchi S., Dianzani U., Di Benedetto D., Esposto E., Faggiano F., Falaschi Z., Ferrante D., Ferrero A., Gagliardi I., Gaidano G., Galbiati A., Gallo S., Garavelli P. L., Gardino C. A., Garzaro M., Gastaldello M. L., Gavelli F., Gennari A., Giacomini G. M., Giacone I., Giai Via V., Giolitti F., Gironi L. C., Gramaglia C., Grisafi L., Inserra I., Invernizzi M., Krengli M., Labella E., Landi I. C., Landi R., Leone I., Lio V., Lorenzini L., Maconi A., Malerba M., Manfredi G. F., Martelli M., Marzari L., Marzullo P., Mennuni M., Montabone C., Morosini U., Mussa M., Nerici I., Nuzzo A., Olivieri C., Padelli S. A., Panella M., Parisini A., Pasche A., Pau A., Pedrinelli A. R., Percivale I., Re R., Rigamonti C., Rizzi E., Rognoni A., Roveta A., Salamina L., Santagostino M., Saraceno M., Savoia P., Sciarra M., Schimmenti A., Scotti L., Spinoni E., Smirne C., Tarantino V., Tillio P. A., Vaschetto R., Vassia V., Zagaria D., Zavattaro E., Zeppegno P., Zottarelli F., and Sainaghi P. P.

Abstract

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk.

Published
2020

12. Pegylated interferon α plus ribavirin for the treatment of chronic hepatitis C: A multicentre independent study supported by the Italian Drug Agency

Author

Rosina, Floriano, Tosti, Maria Elena, Borghesio, Elisabetta, Masocco, Maria, Mele, Alfonso, Coppola, Carmine, Milella, Michele, Borgia, Guglielmo, Andreone, Pietro, Koch, Maurizio, Zignego, Anna Linda, Romano, Mario, Carrara, Maurizio, Almasio, Piero Luigi, Azzola, Emilio, Nardone, Gerardo, Benedetti, Antonio, Carosi, Giampiero, Mazzotta, Francesco, Sagnelli, Evangelista, Rizzetto, Mario, Mascolo, M. C., Cursaro, C., Scuteri, A., Crespi, C., Gianstefani, A., Ranieri, J., Monti, M., Corti, G., Blanc, P. L., Baragli, F., Bellentani, S., Gasbarrini, A., Pompili, M., Mecenate, F., Picardi, A., Vespasiani, U., Nosotti, Null, Null, A. Picardi, Ricci, G. L., Paffetti, A., Mastropietro, C., Moretti, A., Spagnolo, A. L., Puoti, C., Bellis, L., Regazzetti, A., Maffezzini, E., Pietrangelo, A., Abbati, G., Borghi, A., Sardini, C., Raimondo, G., Scribano, L., Martines, D., Svegliati Baroni, G., Faraci, G., Schi anchi, S., Fornaciari, G., Massari, M., Fabris, P., Bertin, T., Salvagnini, M., Madonia, S., Calì, A., Civitavecchia, G., Pirisi, M., Smirne, C., Andreoletti, M., Morisco, F., Caporaso, N., Gentile, I., Brancaccio, G., Gaeta, G. B., Liberti, A., Iannece, M. D., Rocco, A., Federico, A., Loguercio, C., Riegler, G., Esposito, P., Fargion, S., Fatta, E., Masutti, F., Bonaventura, M. E., Autolitano, A., Russello, M., Bellia, A., Toniutto, P., Bitetto, D., Pasulo, L., Lucà, M. G., Grattagliano, I., Palasciano, G., Romagno, D., Giannelli, G., Napoli, N., Plattella, M. S., Cassano, P., Gobbo, G., Monti, V., Raspanti, A., Cuccorese, Null, Colombo, A. E., Mandelli, G., Spinzi, G. C., Floridia, Null, Messina, V., Bonfante, S., Bellissima, P., Toti, M., Vecchiet, J., Falasca, K., Portelli, V., Stefano, G. De, Pietromatera, G., Viganò, P., Re, T., Andreoni, M., Null, G. Raineri, Grossi, P. A., Caputo, S., Cassola, G., Feasi, M., Biagio, A. Di, Nicolini, LAURA AMBRA, Giannini, EDOARDO GIOVANNI, Corbo, M., Foti, G., Kunkar, A., Caterini, L., Migliorini, D., Chiodera, A., Calleri, G., Spezia, C., Framarin, L., Null, M. Berrutti, Ciancio, A., Baiguera, C., Puoti, M., Vento, S., Contini, C., Boccia, S., Casiraghi, M. A., Simone, L., Tacconi, D., Caremani, M., Almi, P., Chimenti, M., Cosco, Null, Messeri, D., Esperti, F. C., Lomonaco, L., Pazzi, P., Fornari, F., Comparato, G., Casetti, T., Foschi, F. G., Samori, A., Ferretti, E., Marin, R., Campo, N., Testa, R., Rizzo, S., Rosina, F, Tosti, ME, Borghesio, E, Masocco, M, Mele, A, Coppola, C, Milella, M, Borgia, G, Andreone, P, Koch, M, Zignego, AL, Romano, M, Carrara, M, Almasio, PL, Azzola, E, Nardone, G, Benedetti, A, Carosi, G, Mazzotta, F, Sagnelli, E, Rizzetto, M, Rosina, F., Tosti, M. E., Borghesio, E., Masocco, M., Mele, A., Coppola, C., Milella, M., Borgia, Guglielmo, Andreone, P., Koch, M., Zignego, A. L., Romano, M., Carrara, M., Almasio, P. L., Azzola, E., Nardone, GERARDO ANTONIO PIO, Benedetti, A., Carosi, G., Mazzotta, F., Sagnelli, E., Rizzetto, M., Aifa, Aisf, Simit, Aigo, Sige, Gentile, Ivan, Morisco, Filomena, Et, Al, Floriano Rosina, Maria Elena Tosti, Elisabetta Borghesio, Maria Masocco, Alfonso Mele, Carmine Coppola, Michele Milella, Guglielmo Borgia, Pietro Andreone, Maurizio Koch, Anna Linda Zignego, Mario Romano, Maurizio Carrara, Piero Luigi Almasio, Emilio Azzola, Gerardo Nardone, Antonio Benedetti, Giampiero Carosi, Francesco Mazzotta, Evangelista Sagnelli, and Mario Rizzetto

Subjects
Registrie, Male, Cirrhosis, medicine.disease_cause, Polyethylene Glycol, Gastroenterology, Polyethylene Glycols, chemistry.chemical_compound, Hepatitis Viruses, Hepatitis Viruse, Prospective Studies, Viral, Registries, Chronic, Prospective cohort study, Drug Carrier, Drug Carriers, Settore MED/12 - Gastroenterologia, Medicine (all), Recombinant Protein, Middle Aged, Hepatitis C, Recombinant Proteins, Treatment Outcome, Italy, Combination, RNA, Viral, Population study, Drug Therapy, Combination, Female, Human, medicine.medical_specialty, Genotype, Hepatitis C virus, Alpha interferon, Ribavirin, Sustained virological response (SVR), Treatment, Antiviral Agents, Follow-Up Studie, Hepatology, Drug Therapy, Internal medicine, medicine, Humans, Antiviral Agent, business.industry, Interferon-alpha, HCV therapy, Hepatitis C, Chronic, medicine.disease, Clinical trial, Prospective Studie, chemistry, Immunology, RNA, Follow-Up Studies, business
Abstract

a b s t r a c t Background: Data on the efficacy of Peg-interferon/ribavirin therapy for chronic hepatitis C are mostly derived from treatment of selected patients enrolled in clinical trials. This study aimed to assess the effectiveness of Peg-interferon/ribavirin therapy in “real world” chronic hepatitis C patients in Italy. Methods: Independent observational multicentre study including consecutive patients receiving Peginterferon/ribavirin in the 18 months before (retrospective phase) and after (prospective phase) the start of the study. Results: 4176 patients were eligible. The final study population consisted of 2051 patients in the retrospective and 2073 in the prospective phase. Sustained virological response was achieved by 1036 patients (50.5%) during the retrospective phase: 325 were genotypes 1/4 (34.1%) and 684 were genotypes 2/3 (67.2%) and by 800 patients (38.6%) during the prospective phase: 300 were genotypes 1/4 (28.4%) and 473 were genotypes 2/3 (51.5%). During multivariate analysis genotypes 2/3 were significantly associated with higher sustained virological response rates; cirrhosis and -glutamil-transpeptidase >2 times the normal limit were associated with poorer response. Conclusions: The response to Peg-interferon/ribavirin therapy in “real world” clinical practice is distinctly lower than in registration trials. The difference in response rates was more pronounced among easy-totreat than among difficult-to-treat hepatitis C virus genotypes.

Published
2014

13. The ALBI Grade Provides Objective Hepatic Reserve Phenotyping across Each BCLC Stage of Hepatocellular Carcinoma

Author

Pinato, D.J., primary, Sharma, R., additional, Yen, C., additional, Arizumi, T., additional, Bettinger, D., additional, Jang, J.W., additional, Smirne, C., additional, Kim, Y.W., additional, Kudo, M., additional, Howell, J., additional, Ramaswami, R., additional, Burlone, M.E., additional, Guerra, V., additional, Thimme, R., additional, Ishizuka, M., additional, Pirisi, M., additional, Stebbing, J., additional, Kubota, K., additional, and Carr, B.I., additional

Published
2016
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15. Apolipoprotein E genotypes modulate fibrosis progression in patients with chronic hepatitis C and persistently normal transaminases

Author

Fabris, C., Vandelli, C., Toniutto, Pierluigi, Minisini, R., Colletta, C., Falleti, Edmondo, Smirne, C., and Pirisi, Mario

Subjects
Adult, Liver Cirrhosis, Male, Time Factors, Adolescent, Biopsy, European Continental Ancestry Group, Risk Assessment, White People, Body Mass Index, Young Adult, Apolipoproteins E, Genetic, Risk Factors, Humans, Genetic Predisposition to Disease, Chronic, Polymorphism, Child, Chi-Square Distribution, Polymorphism, Genetic, Alanine Transaminase, Hepatitis C, Chronic, Middle Aged, Prognosis, Hepatitis C, Cholesterol, Logistic Models, Phenotype, Italy, Disease Progression, Biological Markers, Female, Follow-Up Studies, Biomarkers
Abstract

Carriage of the apolipoprotein E (Apo E) variants, E2, E3 and E4, affects cholesterol metabolism and may be involved in the persistence of hepatitis C virus (HCV) infection. Our aim was to verify whether carriage of specific Apo E variants modulates the course of hepatitis C.We studied a cohort of 116 HCV-positive patients (49 male subjects) with persistently normal transaminases and an Ishak staging score ≤ 2 at an initial biopsy. These untreated patients underwent regular clinical monitoring (median histological follow up: 10 years). Apo E variants were genotyped and results were related to the histological outcome.The mean ± standard deviation staging scores were 0.9 ± 0.7 at entry versus 1.9 ± 1.2 at the end of follow up, P0.0001. Initial and final staging scores in the E3/E3 homozygotes (n = 74) were 1.0 ± 0.7 versus 2.1 ± 1.3, P0.0001, while in the remaining patients (n = 42) they were 0.9 ± 0.6 versus 1.5 ± 1.0, P0.002. A synergistic effect was observed between Apo E polymorphisms and baseline serum cholesterol values: patients not carrying any E3 allele, as well as carriers of a single E3 allele with serum cholesterol concentration190 mg/dL were more likely to have a favorable outcome (final vs initial staging score increased in 7/66, did not change in 10/46, and decreased in 3/4, P0.005).Some of the variability in the natural history of patients with persistently normal transaminases with initially mild hepatitis C can be related to their Apo E genetic background.

Published
2011

17. ACE genotype, body weight changes and target organ damage in renal transplant recipients

Author

Stratta, P., Smirne, C., Fangazio, S., Cornella, C., Lazzarich, E., Minisini, R., Pierluigi Toniutto, Fabris, C., Barbé, C., and Pirisi, M.

Subjects
Adult, Male, Time Factors, Genotype, Graft Survival, DNA, Middle Aged, Peptidyl-Dipeptidase A, Prognosis, Weight Gain, Kidney Transplantation, Young Adult, Gene Frequency, Humans, Female, Alleles, Aged, Follow-Up Studies, Retrospective Studies
Abstract

Carriage of the angiotensin-converting enzyme (ACE) D-allele favors weight gain in mid-life and, possibly, cardiovascular complications; we aimed to verify the relationship between these conditions and ACE polymorphisms in the renal transplant (RTx) setting.ACE genotypes were evaluated in 169 RTx recipients (107 males, 62 females) and related to body mass index (BMI; kg/m2) changes 1 year after transplant, as well as to cardiovascular events and allograft loss. Allelic frequencies and body weights were compared with those of a control group (age- and sex-matched healthy blood donors).Allelic frequencies were 0.639 and 0.669 for the D-allele, and 0.361 and 0.331 for the I-allele, in recipients and controls, respectively (p=NS). In the patient population, carriage of the I/ allele was associated with a BMI23 at the time of RTx (p0.005). In contrast, in the control group, higher BMI values tended to occur in D/ carriers. Moreover, BMI values were higher in the control group (24.7 -/+ 3.5 vs. 23.6 -/+ 3.3, p=0.003) but, 1 year after RTx, this difference was nullified. At multivariate analysis, the factors associated with weight gain after RTx were ACE D/D (odds ratio [OR] = 2.35, 95% confidence interval [95% CI], 1.00-5.49) and age at RTxor=49 years (OR=2.82, 95% CI, 1.30-6.13); the factors associated with cardiovascular events and/or allograft loss were cyclosporine-based immunosuppressive regimen (p=0.002), history of smoking (p=0.005) and dyslipidemia (p0.05).Body weight at the time of RTx and weight gain 1 year after RTx, but not cardiovascular complications and allograft loss, are related to the ACE I/D genotype of RTx recipients.

Published
2008

20. [High serum levels of Transforming Growth Factor-beta1, Interleukin-10 and Vascular Endothelial Growth Factor in pancreatic adenocarcinoma patients]

Author

Smirne, C., Camandona, Michele, Alabiso, O., Bellone, G., and Emanuelli, G.

Abstract

Pancreatic adenocarcinomas are among the most aggressive types of cancer with an extremely poor diagnosis. Since this type of cancer is not well amenable to chemo- and radiotherapy or immunotherapy, surgical resection remains the only feasible treatment to date. Transforming Growth Factor (TGF)-beta and Interleukin (IL)-10 are potent immunomodulators that have been shown to suppress several aspects of the immune response. Vascular Endothelial Growth Factor (VEGF) is a powerful angiogenic factor, recently thought to be involved in neoangiogenesis and metastasis spreading. Therefore the three cytokines may contribute, by different pathways, to immune escape and growth of tumor. This study was conducted to determine the possible significance of TGF-beta1, IL-10 and VEGF as markers for monitoring the clinical course of pancreatic adenocarcinoma patients.Cytokine serum levels were measured in 30 pancreatic cancer patients and in 30 age and sex-matched healthy subjects.In comparison to serum concentrations in controls, TGF-beta1, IL-10 and VEGF levels were significantly elevated in all patients. Where the patients were divided by groups on the basis of the clinical stage of the disease, no differences were observed in TGF-beta1 levels among the groups. On the contrary, IL-10 and VEGF were more represented in stage IV patients than in stage II and III patients. In addition, the 14 patients who underwent surgical resection had postoperative cytokine serum levels markedly lower than those observed at diagnosis.Overall, the results suggest the importance of these markers in predicting the biological activity of the disease and suggest new targets for future rational therapies.

Published
2006

25. Chlamydia trachomatis prevalence in North-West Italy

Author

Grio, R., Bello, L., Smirne, C., Francesco D'Addato, Latino, M. A., Corvetto, L., Intinis, G., Spagnolo, E., Maffei, S., and Leotta, E.

Subjects
Adult, Sexually Transmitted Diseases, Bacterial, Adolescent, Ligase Chain Reaction, Chlamydia trachomatis, Chlamydia Infections, Middle Aged, Statistics, Nonparametric, Uterine Cervicitis, Sexual Partners, Italy, Risk Factors, Surveys and Questionnaires, Prevalence, Humans, Mass Screening, Female, Child, Endometritis, Retrospective Studies
Abstract

Chlamydia (C.) trachomatis infection is the most common sexually transmitted disease (STD) among sexually active adolescents and young adults in Europe. The aim of this study was to determine the prevalence of C. trachomatis among sexually active women in Piedmont, Italy and the correlation between some risk factors and C. trachomatis infection.In our study 31,419 sexually active women aged 12-55 were screened for C. trachomatis by Abbott's ligase chain reaction (LCR) using cervical swabs during the period 1997-2001 at St. Anna Obstetric-Gynecological Hospital, Turin. All the patients answered a specific questionnaire.In our analysis the prevalence of C. trachomatis infection was found to be 1.23%, and the average age among the infected patients was 36.98 years. Statistical analysis was performed using the chi squared test; a p0.05 was considered significant. A correlation was found between a positive test result and the age at the first intercourse (p0.001), the number of sexual partners in the preceding 6 months (p0.001), the presence of symptoms (p0.001), a low level of education (p0.001) and an East-European and Central-Northern African citizenship (p0.001). No statistically significant differences were found among the contraceptive methods used, whether an hormonal or a barrier type; a marked increment of the risk was observed when no contraception was used.Frequent microbiological examinations are desirable for patients whose anamnesis shows an augmented risk of contracting sexually transmitted infections in order to avoid long term complications from misdiagnosed or asymptomatic pathologies, as often happens with C. trachomatis.

Published
2004

29. [The pro-apoptotic factors Fas Ligand and Trail. Molecular mechanisms, physiopathological role and therapeutic potential]

Author

Busso, V, Smirne, C, Ferrero, Ivana, Segir, R, Abrate, S, Bellone, G, and Emanuelli, G.

Subjects
Receptors, TNF-Related Apoptosis-Inducing Ligand, Fas Ligand Protein, Membrane Glycoproteins, Receptors, Animals, Humans, Apoptosis, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Signal Transduction
Abstract

Programmed cell death, also known as apoptosis, is a normal physiologic process which occurs during embryonic development as well as in maintenance of tissue homeostasis. Increasing evidence suggests that alterations in cell death contribute to the pathogenesis of a number of human diseases, including cancer, viral infections, autoimmune diseases and acquired immunodeficiency syndrome (AIDS). The extraordinary research activity of the past few years has resulted in the characterization of the principal proteins involved in the apoptosis machinery. An area of particular interest has been the induction of apoptosis by two death receptor/ligand pairs, Fas/Fas Ligand and DR4-DR5/TRAIL. The identification of these molecules with the recruited signaling pathways could clarify their physiopathological implications, having a significant impact upon potential therapeutic interventions in diseases associated with cell survival alterations.

Published
2001

36. 1155 IINTERLEUKIN 28B RS12979860 C/T POLYMORPHISM AND SERUM CHOLESTEROL AS PREDICTORS OF FIBROSIS PROGRESSION IN PATIENTS WITH CHRONIC HEPATITIS C AND PERSISTENTLY NORMAL TRANSAMINASES

Author

Fornasiere, E., primary, Cmet, S., additional, Bitetto, D., additional, Cussigh, A., additional, Fumólo, E., additional, Bignulin, S., additional, Fontanini, E., additional, Colletta, C., additional, Vandelli, C., additional, Ceriani, E., additional, Smirne, C., additional, Bignulin, E., additional, Falleti, E., additional, Fabris, C., additional, Toniutto, P., additional, and Pirisi, M., additional

Published
2011
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37. T-9 Interleukin 28B rs12979860 C/T polymorphism and serum cholesterol as predictors of fibrosis progression in patients with chronic hepatitis C and persistently normal transaminases

Author

Fornasiere, E., primary, Cmet, S., additional, Bitetto, D., additional, Cussigh, A., additional, Fumolo, E., additional, Bignulin, S., additional, Fontanini, E., additional, Colletta, C., additional, Vandelli, C., additional, Ceriani, E., additional, Smirne, C., additional, Bignulin, E., additional, Falleti, E., additional, Fabris, C., additional, Toniutto, P., additional, and Pirisi, M., additional

Published
2011
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38. 688 IL6 POLYMORPHISMS PLAY A ROLE IN INFLUENCING THE HISTOLOGICAL PROGRESSION IN PATIENTS WITH CHRONIC HCV INFECTION AND NORMAL TRANSAMINASES

Author

Fornasiere, E., primary, Vandelli, C., additional, Falleti, E., additional, Colletta, C., additional, Fontanini, E., additional, Camet, S., additional, Cussigh, A., additional, Bitetto, D., additional, Smirne, C., additional, Minisini, R., additional, Fabris, C., additional, Toniutto, P., additional, and Pirisi, M., additional

Published
2010
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40. T.N.34 IL6 POLYMORPHISMS PLAY A ROLE IN INFLUENCING THE HISTOLOGICAL PROGRESSION IN PATIENTS WITH CHRONIC HCV INFECTION AND NORMAL TRANSAMINASES

Author

Fornasiere, E., primary, Vandelli, C., additional, Falleti, E., additional, Colletta, C., additional, Fontanini, E., additional, Cmet, S., additional, Cussigh, A., additional, Bitetto, D., additional, Smirne, C., additional, Minisini, R., additional, Fabris, C., additional, Toniutto, P., additional, and Pirisi, M., additional

Published
2010
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44. [725] INSULIN RESISTANCE, INSULIN SECRETION AND

Author

Limoncini, A., primary, Smirne, C., additional, Corliano, F., additional, Marconi, C., additional, Scaglia, E., additional, Carnevale, G., additional, Toniutto, P., additional, Fabris, C., additional, and Pirisi, M., additional

Published
2007
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47. 2 OP C-kit proto-oncogene and the cell associated forms of its ligand stem cell factor are differentially expressed in normal, premalignant and malignant lesions of colon mucosa

Author

Tibaudi, D., primary, Carbone, A., additional, Smirne, C., additional, Ferrero, I., additional, Sozzi, M., additional, Gramigni, C., additional, Nano, M., additional, Dughera, L., additional, Bellone, G., additional, Dei Poli, M., additional, and Emanuelli, G., additional

Published
2002
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49. Aberrant activation of c-kit protects colon carcinoma cells against apoptosis and enhances their invasive potential

Author

Bellone, G., Carbone, A., Sibona, N., Bosco, O., Tibaudi, D., Smirne, C., Martone, T., Gramigni, C., Michele Camandona, Emanuelli, G., and Rodeck, U.

Subjects
Stem Cell Factor, Antibodies, Monoclonal, Down-Regulation, Apoptosis, SCF, colon carcinoma, Oligonucleotides, Antisense, Enzyme Activation, Proto-Oncogene Proteins c-kit, Phenotype, Matrix Metalloproteinase 9, Cell Movement, c-kit, Colonic Neoplasms, Cell Adhesion, Tumor Cells, Cultured, Humans, Matrix Metalloproteinase 2, Neoplasm Invasiveness, Cell Division
Abstract

Multiple genetic aberrations contribute to the development of biologically aggressive, clinically malignant colorectal carcinomas (CRCs). Some of these have been linked to inappropriate signaling through the tyrosine kinase moieties of growth factor receptors. We have described previously (G. Bellone et al., J. Cell. Physiol., 172: 1-11, 1997) that human CRCs overexpress both the receptor tyrosine kinase c-kit and its ligand, stem cell factor (SCF), relative to normal mucosa cells, thus establishing an autocrine c-kit-mediated loop. In addition, we noted that exogenous SCF contributes to anchorage-independent growth of HT-29 colon carcinoma cells in semisolid medium. Here, we investigated possible roles of the c-kit/SCF autocrine/paracrine system in survival and invasive capacity of DLD-1 colon carcinoma cells. We report that SCF was required for migration and invasion of DLD-1 cells through reconstituted basement membranes (Matrigel) and up-regulated gelatinase (matrix metalloproteinase-9) activity in DLD-1 cells. Furthermore, we describe that SCF supported survival of DLD-1 cells in growth factor-deprived conditions. These results suggest multiple roles of c-kit activation in support of the malignant phenotype of DLD-1 cells related to growth, survival, migration, and invasive potential.

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