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1. Radioimmunotherapy versus autologous hematopoietic stem cell transplantation in relapsed/refractory follicular lymphoma: a Fondazione Italiana Linfomi multicenter, randomized, phase III trial

Author

Ladetto, M., Tavarozzi, R., Zanni, M., Evangelista, A., Ferrero, S., Tucci, A., Botto, B., Bolis, S., Volpetti, S., Zilioli, V.R., Puccini, B., Arcari, A., Pavone, V., Gaidano, G., Corradini, P., Tani, M., Cavallo, F., Milone, G., Ghiggi, C., Pinto, A., Pastore, D., Ferreri, A.J.M., Latte, G., Patti, C., Re, F., Benedetti, F., Luminari, S., Pennese, E., Bossi, E., Boccomini, C., Anastasia, A., Bottelli, C., Ciccone, G., and Vitolo, U.

Published
2024
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2. Radioimmunotherapy versus autologous hematopoietic stem cell transplantation in relapsed/refractory follicular lymphoma: a Fondazione Italiana Linfomi multicenter, randomized, phase III trial

Author

Ladetto, M., primary, Tavarozzi, R., additional, Zanni, M., additional, Evangelista, A., additional, Ferrero, S., additional, Tucci, A., additional, Botto, B., additional, Bolis, S., additional, Volpetti, S., additional, Zilioli, V.R., additional, Puccini, B., additional, Arcari, A., additional, Pavone, V., additional, Gaidano, G., additional, Corradini, P., additional, Tani, M., additional, Cavallo, F., additional, Milone, G., additional, Ghiggi, C., additional, Pinto, A., additional, Pastore, D., additional, Ferreri, A.J.M., additional, Latte, G., additional, Patti, C., additional, Re, F., additional, Benedetti, F., additional, Luminari, S., additional, Pennese, E., additional, Bossi, E., additional, Boccomini, C., additional, Anastasia, A., additional, Bottelli, C., additional, Ciccone, G., additional, and Vitolo, U., additional

Published
2023
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3. Differences among young adults, adults and elderly chronic myeloid leukemia patients

Author

Salvi, F., Pini, M., Leoni, P., Rupoli, S., Galieni, P., Bigazzi, C., Cantore, N., Palmieri, F., Albano, F., Russo Rossi, A., Rambaldi, A., Intermesoli, T., Palandri, F., Testoni, N., Luatti, S., Soverini, S., Iacobucci, I., Bochicchio, M.T., Apolinari, M., Fogli, M., Cervello, I., Capucci, A., Malagola, M., Malpignano, A., Girasoli, M., Angelucci, E., Usala, E., Storti, S., De Biasi, E., Tagariello, G., Sartori, R., Di Raimondo, F., Vigneri, P., Impera, S., Molica, S., Lanza, F., Viganò, C., Grasso, M., Rapezzi, D., Cavazzini, F., Bosi, A., Santini, V., Capalbo, S.F., Spinosa, G., Pierri, I., Bergamaschi, M., Carella, A.M., Bacigalupo, A., De Blasio, A., Ciccone, F., Di Renzo, N., Musolino, C., Russo, S., Cortelezzi, A., Morra, E., Pungolino, E.M., Luppi, M., Marasca, R., Pogliani, E.M., Gambacorti-Passerini, C., Luciano, L., Ferrara, F., Annunziata, M., Latte, G., Noli, D., Rege-Cambrin, G., Fava, C., Semenzato, G., Binotto, G., Fabbiano, F., Turri, D., Siragusa, S., Caracciolo, C., Musso, M., Porretto, F., Aversa, F., Crugnola, M., Cazzola, M., Orlandi, E., Falini, B., Falzetti, F., Visani, G., Isidori, A., Fioritoni, G., Di Lorenzo, R., Vallisa, D., Trabacchi, E., Petrini, M., Galimberti, S., Pizzuti, M., Zaccaria, A., Salvucci, M., Ronco, F., Ielo, D., Merli, F., Avanzini, P., Tosi, P., Merli, A., Musto, P., De Stefano, V., Sica, S., Latagliata, R., De Fabritiis, P., Trawiska, M., Majolino, I., Pacilli, L., Ronci, B., Cedrone, M., Petti, M.C., Pisani, F., Tafuri, A., Montefusco, E., Iuliano, F., Dore, F., Pardini, S., Bocchia, M., Defina, M., Liberati, A.M., Luzzi, D., Boccadoro, M., Ferrero, D., Vitolo, U., Gherlinzoni, F., Calistri, E., Fanin, R., Pizzolo, G., Meneghini, V., Rodighiero, F., D'Emilio, A., Castagnetti, F., Gugliotta, G., Baccarani, M., Breccia, M., Specchia, G., Levato, L., Abruzzese, E., Rossi, G., Iurlo, A., Martino, B., Pregno, P., Stagno, F., Cuneo, A., Bonifacio, M., Gobbi, M., Russo, D., Gozzini, A., Tiribelli, M., de Vivo, A., Alimena, G., Cavo, M., Martinelli, G., Pane, F., Saglio, G., and Rosti, G.

Published
2015
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4. S113: NATIONAL PEGASPARGASE-MODIFIED RISK-ORIENTED PROGRAM FOR PHILADELPHIA-NEGATIVE ADULT ACUTE LYMPHOBLASTIC LEUKEMIA/LYMPHOBLASTIC LYMPHOMA (PH− ALL/LL). GIMEMA LAL 1913 FINAL RESULTS.

Author

Bassan, R., primary, Chiaretti, S., additional, Della Starza, I., additional, Spinelli, O., additional, Santoro, A., additional, Elia, L., additional, De Propris, M. S., additional, Scattolin, A. M., additional, Paoloni, F., additional, Messina, M., additional, Audisio, E., additional, Marbello, L., additional, Borlenghi, E., additional, Zappasodi, P., additional, Vetro, C., additional, Martinelli, G., additional, Mattei, D., additional, Fracchiolla, N., additional, Bocchia, M., additional, De Fabritiis, P., additional, Bonifacio, M., additional, Candoni, A., additional, Cassibba, V., additional, Di Bartolomeo, P., additional, Latte, G., additional, Trappolini, S., additional, Guarini, A., additional, Vitale, A., additional, Fazi, P., additional, Vignetti, M., additional, Rambaldi, A., additional, and Foà, R., additional

Published
2022
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5. P1144: RADIOIMMUNOTHERAPY (RIT) VERSUS AUTOLOGOUS HEMATOPOIETIC STEM-CELL TRANSPLANTATION (ASCT) IN RELAPSED/REFRACTORY (R/R) FOLLICULAR LYMPHOMA: A FONDAZIONE ITALIANA LINFOMI (FIL) PHASE III TRIAL.

Author

Ladetto, M., primary, Tavarozzi, R., additional, Evangelista, A., additional, Zanni, M., additional, Tucci, A., additional, Anastasia, A., additional, Botto, B., additional, Boccomini, C., additional, Bolis, S., additional, Volpetti, S., additional, Zilioli, V. R., additional, Puccini, B., additional, Arcari, A., additional, Pavone, V., additional, Gaidano, G., additional, Corradini, P., additional, Tani, M., additional, Ferrero, S., additional, Cavallo, F., additional, Milone, G., additional, Ghiggi, C., additional, Pinto, A., additional, Pastore, D., additional, Ferreri, A. J., additional, Latte, G., additional, Patti, C., additional, Re, F., additional, Arcaini, L., additional, Benedetti, F., additional, Usai, S. V., additional, Luminari, S., additional, Mannina, D., additional, Pulsoni, A., additional, Stelitano, C., additional, Pennese, E., additional, Pietrantuono, G., additional, Gherlinzoni, F., additional, Pomponi, F., additional, Olivieri, A., additional, Perrone, T., additional, Rota Scalabrini, D., additional, Califano, C., additional, Falini, B., additional, Ciccone, G., additional, and Vitolo, U., additional

Published
2022
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6. Differences among young adults, adults and elderly chronic myeloid leukemia patients

Author

Castagnetti, F., Gugliotta, G., Baccarani, M., Breccia, M., Specchia, G., Levato, L., Abruzzese, E., Rossi, G., Iurlo, A., Martino, B., Pregno, P., Stagno, F., Cuneo, A., Bonifacio, M., Gobbi, M., Russo, D., Gozzini, A., Tiribelli, M., de Vivo, A., Alimena, G., Cavo, M., Martinelli, G., Pane, F., Saglio, G., Rosti, G., Salvi, F., Pini, M., Leoni, P., Rupoli, S., Galieni, P., Bigazzi, C., Cantore, N., Palmieri, F., Albano, F., Russo Rossi, A., Rambaldi, A., Intermesoli, T., Palandri, F., Testoni, N., Luatti, S., Soverini, S., Iacobucci, I., Bochicchio, MT., Apolinari, M., Fogli, M., Cervello, I., Capucci, A., Malagola, M., Malpignano, A., Girasoli, M., Angelucci, E., Usala, E., Storti, S., De Biasi, E., Tagariello, G., Sartori, R., Di Raimondo, F., Vigneri, P., Impera, S., Molica, S., Lanza, F., Viganò, C., Grasso, M., Rapezzi, D., Cavazzini, F., Bosi, A., Santini, V., Capalbo, SF., Spinosa, G., Pierri, I., Bergamaschi, M., Carella, AM., Bacigalupo, A., De Blasio, A., Ciccone, F., Di Renzo, N., Musolino, C., Russo, S., Cortelezzi, A., Morra, E., Pungolino, EM., Luppi, M., Marasca, R., Pogliani, EM., Gambacorti-Passerini, C., Luciano, L., Ferrara, F., Annunziata, M., Latte, G., Noli, D., Rege-Cambrin, G., Fava, C., Semenzato, G., Binotto, G., Fabbiano, F., Turri, D., Siragusa, S., Caracciolo, C., Musso, M., Porretto, F., Aversa, F., Crugnola, M., Cazzola, M., Orlandi, E., Falini, B., Falzetti, F., Visani, G., Isidori, A., Fioritoni, G., Di Lorenzo, R., Vallisa, D., Trabacchi, E., Petrini, M., Galimberti, S., Pizzuti, M., Zaccaria, A., Salvucci, M., Ronco, F., Ielo, D., Merli, F., Avanzini, P., Tosi, P., Merli, A., Musto, P., De Stefano, V., Sica, S., Latagliata, R., De Fabritiis, P., Trawiska, M., Majolino, I., Pacilli, L., Ronci, B., Cedrone, M., Petti, MC., Pisani, F., Tafuri, A., Montefusco, E., Iuliano, F., Dore, F., Pardini, S., Bocchia, M., Defina, M., Liberati, AM., Luzzi, D., Boccadoro, M., Ferrero, D., Vitolo, U., Gherlinzoni, F., Calistri, E., Fanin, R., Pizzolo, G., Meneghini, V., Rodighiero, F., and DʼEmilio, A.

Published
2015
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8. Lenalidomide treatment of myelodysplastic syndromes with chromosome 5q deletion: Results from the National Registry of the Italian Drug Agency

Author

Arcioni, F., Roncadori, A., Di Battista, V., Tura, S., Covezzoli, A., Cundari, S., Mecucci, C., Abbadessa, A., Alterini, R., Santini, V., Cantonetti, M., Buccisano, F., Bacigalupo, A., Sessarego, M., Tonso, A., Ferrero, D., D'Ardia, S., Tarella, C., Cascavilla, N., Bassan, R., Sancetta, R., Cortelezzi, A., Reda, G., Maria D'Arco, A., De Fabritiis, P., Di Renzo, N., Falini, B., Alimena, G., Avanzini, P., Ilariucci, F., Iuliano, F., La Nasa, G., Caocci, G., Defina, M., Latte, G., Palmas, A., Levis, A., Leone, G., Teresa Voso, M., Leoni, P., Poloni, A., Fozza, C., Crugnola, M., Montanaro, M., Spedini, P., Lanza, F., Pizzuti, M., Pane, F., Paolini, R., Borin, L., Rambaldi, A., Rossi, G., Maria Pelizzari, A., Russo, D., D'Emilio, A., Ruggeri, M., Semenzato, G., Specchia, G., Tagariello, G., Sartori, R., Testore, F., Ciravegna, G., Marasca, R., Cimarosto, L., Fontanive, O., Visani, G., Arcioni, F., Roncadori, A., Di Battista, V., Tura, S., Covezzoli, A., Cundari, S., Mecucci, C., Abbadessa, A., Alterini, R., Santini, V., Cantonetti, M., Buccisano, F., Bacigalupo, A., Sessarego, M., Tonso, A., Ferrero, D., D'Ardia, S., Tarella, C., Cascavilla, N., Bassan, R., Sancetta, R., Cortelezzi, A., Reda, G., Maria D'Arco, A., De Fabritiis, P., Di Renzo, N., Falini, B., Alimena, G., Avanzini, P., Ilariucci, F., Iuliano, F., La Nasa, G., Caocci, G., Defina, M., Latte, G., Palmas, A., Levis, A., Leone, G., Teresa Voso, M., Leoni, P., Poloni, A., Fozza, C., Crugnola, M., Montanaro, M., Spedini, P., Lanza, F., Pizzuti, M., Pane, F., Paolini, R., Borin, L., Rambaldi, A., Rossi, G., Maria Pelizzari, A., Russo, D., D'Emilio, A., Ruggeri, M., Semenzato, G., Specchia, G., Tagariello, G., Sartori, R., Testore, F., Ciravegna, G., Marasca, R., Cimarosto, L., Fontanive, O., and Visani, G.

Subjects
Oncology, Myeloid, Male, Group B, Immunologic Factor, 0302 clinical medicine, Retrospective Studie, hemic and lymphatic diseases, del(5q), Prospective Studies, Registries, Prospective cohort study, Hematology, Leukemia, registry study, Standard treatment, Remission Induction, General Medicine, Middle Aged, lenalidomide, myelodysplastic syndromes, Aged, Chromosomes, Human, Pair 5, Disease Progression, Female, Humans, Immunologic Factors, Italy, Karyotyping, Lenalidomide, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Retrospective Studies, Thalidomide, Chromosome Deletion, 030220 oncology & carcinogenesis, Pair 5, medicine.drug, Human, medicine.medical_specialty, Myelodysplastic Syndrome, Acute, Chromosomes, NO, 03 medical and health sciences, Internal medicine, medicine, business.industry, Myelodysplastic syndromes, Retrospective cohort study, medicine.disease, Settore MED/15, Prospective Studie, business, 030215 immunology
Abstract

Objective The most typical cytogenetic aberration in myelodysplastic syndromes is del(5q), which, when isolated, is associated with refractory anaemia and good prognosis. Based on high rates of erythroid response and transfusion independence, Lenalidomide (LEN) became the standard treatment. This multi-centre study was designed to supplement Italian Registry data on LEN by addressing prescription, administration appropriateness, haematological and cytogenetic responses and disease evolution. Methods MORE study was an observational, non-interventional, multi-centre, retrospective and prospective study. Cases were recruited from 45 Haematological Centres throughout Italy. Data were collected from the Italian National Registry for Lenalidomide administration and supplemented by a MORE data form. Results Data from 190/213 patients were analysed. In all, 149 had been diagnosed by conventional cytogenetics (GROUP A) and 41 only by FISH (GROUP B). Overall erythroid response was obtained in 92.8% of cases. Overall cytogenetic remission was achieved in 22.6% of cases. Disease progression occurred in 15.6% of cases. Clonal cytogenetic evolution characterised progression to AML but not to higher risk MDS. Conclusions Erythroid response to Lenalidomide was similar in MDS with isolated del(5q) and with del(5q) plus one anomaly. Progression to AML or higher risk MDS showed different cytogenetic features.

Published
2018

10. Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study

Author

Mohty, M. Terpos, E. Mateos, M.-V. Cavo, M. Lejniece, S. Beksac, M. Bekadja, M.A. Legiec, W. Dimopoulos, M. Stankovic, S. Durán, M.S. De Stefano, V. Corso, A. Kochkareva, Y. Laane, E. Berthou, C. Salwender, H. Masliak, Z. Pečeliūnas, V. Willenbacher, W. Silva, J. Louw, V. Nemet, D. Borbényi, Z. Abadi, U. Pedersen, R.S. Černelč, P. Potamianou, A. Couturier, C. Feys, C. Thoret-Bauchet, F. Boccadoro, M. Bekadja, M. Hamladji, R.-M. Ali, H.A. Hamdi, S. Touhami, H. Mansour, N.S. Linkesch, W. Abildgaard, N. Hein, M. Eveillard, J.R. Yamani, A.E. Moreau, P. Sanhes, L. Lepeu, G. Laribi, K. Jourdan, E. Fitoussi, O. Allangba, O. Fleury, J. Escoffre, M. Benramdane, R. Cartron, G. Dine, G. Legouffe, E. Harich, H.-D. Illmer, T. Dörfel, S. Hannig, C.V. Koenigsmann, M. Prange-Krex, G. Tamm, I. Zeller, W. Maasberg, M. Schlag, R. Klausmann, M. Uhlig, J. Alkemper, B. Schütz, S. Tessen, H.-W. Mohr, B. Schmidt, P. Heinrich, B. Hebart, H. Seipelt, G. Zoeller, T. Heits, F. Müller-Naendrup, C. Hansen, R. Repp, R. Von Weikersthal, L.F. Schmits, R. Heßling, J. Krammer-Steiner, B. Janzen, V. Schauer, M. Grüner, M.W. Kisro, J. Denzlinger, C. Freier, W. Junghanss, C. Görner, M. Laichinger, K. Ostermann, H. Dürk, H. Hess, G. Reich, G. Matsouka, P. Pouli, A. Anagnostopoulos, A. Masszi, T. Ivanyi, J. Szomor, A. Nagler, A. Magen, H. Avivi, I. Quitt, M. Palumbo, A. Za, T. Vallisa, D. Foa, R. Bosi, A. Vacca, A. Lanza, F. Palazzo, G. Avvisati, G. Ferrara, F. Consoli, U. Cantonetti, M. Angelucci, E. Califano, C. Di Raimondo, F. Guarini, A. Musso, M. Pizzuti, M. Giuliani, N. Ardizzoia, A. Di Renzo, N. Gaidano, G. Gozzetti, A. Pitini, V. Farina, G. Centurioni, R. De Fabritiis, P. Iuliano, F. La Nasa, G. La Verde, G. Pane, F. Recine, U. La Targia, M. Mineo, G. Cangialosi, C. Fagnani, D. Federici, A. Romano, A. Specchia, G. Storti, S. Bongarzoni, V. Bacigalupo, A. Gobbi, M. Latte, G. Mannina, D. Capalbo, S. Jurgutis, M. Woszczyk, D. Hołojda, J. Gornik, S. Pluta, A. Morawiec-Szymonik, E. Kyrcz-Krzemien, S. Homenda, W. Grosicki, S. Sulek, K. Lange, A. Kloczko, J. Starzak-Gwozdz, J. Hellmann, A. Komarnicki, M. Kuliczkowski, K. Viveiros, C. Gonçalves, C. Esefyeva, N. Kaplanov, K. Volodicheva, E. Laricheva, E. Dergacheva, V. Chukavina, M. Volchenko, N. Nazarova, I. Anchukova, L. Ovanesova, E. Salogub, G. Magomedova, L. Kuznetsova, I. Osyunikhina, S. Serdyuk, O. Karyagina, E. Ivanova, V. Černelč, S.P. Coetzee, C. Gunther, K. Moodley, D. Duran, S. Gutiérrez, A.E. De Oteyza, J.P. Capote, F.J. Casanova, M. Sanchez, J.M. Rios-Herranz, E. Ibañez-Garcia, J. Herranz, M.J. Hernandez, B. Sanchez, S.S. Escalante, F. Carnicero, F. Lleonart, J.B. Gironella, M. Martínez, R. De La Guia, A.L. Palomera, L. Iglesias, R. Ramos, F.S. De La Serna, J. Sanchez, P.G. Vidal, J.B. Morfa, M.D. Beksac, T.-M. Vural, F. Aydin, Y. Unal, A. Goker, H. Bilgir, O. Guvenc, B. Turgut, M. Ozet, G.G. Ali, R. Kyselyova, M. Glushko, N. Vybyrana, R. Skrypnyk, I. Tretyak, N. Kharchevska, T. Dyagil, I. Popovs'ka, T. Shimanskiy, V. Lysa, T. Oliynyk, H. Vilchevskaya, K. Kryachok, I. Popovych, Y. Romanyuk, N. Yushchenko, N. Kaplan, P. Rekhtman, G. Pylypenko, H. Kozlov, V. Drach, J. Harousseau, J.-L. Einsele, H. Goldschmidt, H. Facon, T. Michalet, M. Savchenko, V.G. De la Rubia, J. Cook, G. Mellqvist, U.-H. Ludwig, H. EMMOS Investigators

Abstract

Multiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits. © 2018 The Authors

Published
2018

11. Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study

Author

Mohty, M., Terpos, E., Mateos, M. -V., Cavo, M., Lejniece, S., Beksac, M., Bekadja, M. A., Legiec, W., Dimopoulos, M., Stankovic, S., Duran, M. S., De Stefano, Valerio, Corso, A., Kochkareva, Y., Laane, E., Berthou, C., Salwender, H., Masliak, Z., Peceliunas, V., Willenbacher, W., Silva, J., Louw, V., Nemet, D., Borbenyi, Z., Abadi, U., Pedersen, R. S., Cernelc, P., Potamianou, A., Couturier, C., Feys, C., Thoret-Bauchet, F., Boccadoro, M., Bekadja, M., Hamladji, R. -M., Ali, H. A., Hamdi, S., Touhami, H., Mansour, N. S., Linkesch, W., Abildgaard, N., Hein, M., Eveillard, J. R., Yamani, A. E., Moreau, P., Sanhes, L., Lepeu, G., Laribi, K., Jourdan, E., Fitoussi, O., Allangba, O., Fleury, J., Escoffre, M., Benramdane, R., Cartron, G., Dine, G., Legouffe, E., Harich, H. -D., Illmer, T., Dorfel, S., Hannig, C. V., Koenigsmann, M., Prange-Krex, G., Tamm, I., Zeller, W., Maasberg, M., Schlag, R., Klausmann, M., Uhlig, J., Alkemper, B., Schutz, S., Tessen, H. -W., Mohr, B., Schmidt, P., Heinrich, B., Hebart, H., Seipelt, G., Zoeller, T., Heits, F., Muller-Naendrup, C., Hansen, R., Repp, R., Von Weikersthal, L. F., Schmits, R., Hessling, J., Krammer-Steiner, B., Janzen, V., Schauer, M., Gruner, M. W., Kisro, J., Denzlinger, C., Freier, W., Junghanss, C., Gorner, M., Laichinger, K., Ostermann, H., Durk, H., Hess, G., Reich, G., Matsouka, P., Pouli, A., Anagnostopoulos, A., Masszi, T., Ivanyi, J., Szomor, A., Nagler, A., Magen, H., Avivi, I., Quitt, M., Palumbo, A., Za, Tommaso, Vallisa, D., Foa, R., Bosi, A., Vacca, A., Lanza, F., Palazzo, G., Avvisati, G., Ferrara, F., Consoli, U., Cantonetti, M., Angelucci, E., Califano, C., Di Raimondo, F., Guarini, A., Musso, M., Pizzuti, M., Giuliani, N., Ardizzoia, A., Di Renzo, N., Gaidano, G., Gozzetti, A., Pitini, V., Farina, G., Centurioni, R., De Fabritiis, P., Iuliano, F., La Nasa, G., La Verde, G., Pane, F., Recine, U., La Targia, M., Mineo, G., Cangialosi, C., Fagnani, D., Federici, A., Romano, A., Specchia, G., Storti, Sergio, Bongarzoni, V., Bacigalupo, Andrea, Gobbi, M., Latte, G., Mannina, D., Capalbo, S., Jurgutis, M., Woszczyk, D., Holojda, J., Gornik, S., Pluta, A., Morawiec-Szymonik, E., Kyrcz-Krzemien, S., Homenda, W., Grosicki, S., Sulek, K., Lange, A., Kloczko, J., Starzak-Gwozdz, J., Hellmann, A., Komarnicki, M., Kuliczkowski, K., Viveiros, C., Goncalves, C., Esefyeva, N., Kaplanov, K., Volodicheva, E., Laricheva, E., Dergacheva, V., Chukavina, M., Volchenko, N., Nazarova, I., Anchukova, L., Ovanesova, E., Salogub, G., Magomedova, L., Kuznetsova, I., Osyunikhina, S., Serdyuk, O., Karyagina, E., Ivanova, V., Cernelc, S. P., Coetzee, C., Gunther, K., Moodley, D., Duran, S., Gutierrez, A. E., De Oteyza, J. P., Capote, F. J., Casanova, M., Sanchez, J. M., Rios-Herranz, E., Ibanez-Garcia, J., Herranz, M. J., Hernandez, B., Sanchez, S. S., Escalante, F., Carnicero, F., Lleonart, J. B., Gironella, M., Martinez, R., De La Guia, A. L., Palomera, L., Iglesias, R., Ramos, F. S., De La Serna, J., Sanchez, P. G., Vidal, J. B., Morfa, M. D., Beksac, T. -M., Vural, F., Aydin, Y., Unal, A., Goker, H., Bilgir, O., Guvenc, B., Turgut, M., Ozet, G. G., Ali, R., Kyselyova, M., Glushko, N., Vybyrana, R., Skrypnyk, I., Tretyak, N., Kharchevska, T., Dyagil, I., Popovs'Ka, T., Shimanskiy, V., Lysa, T., Oliynyk, H., Vilchevskaya, K., Kryachok, I., Popovych, Y., Romanyuk, N., Yushchenko, N., Kaplan, P., Rekhtman, G., Pylypenko, H., Kozlov, V., Drach, J., Harousseau, J. -L., Einsele, H., Goldschmidt, H., Facon, T., Michalet, M., Savchenko, V. G., De la Rubia, J., Cook, G., Mellqvist, U. -H., Ludwig, H., De Stefano V. (ORCID:0000-0002-5178-5827), Za T., Storti S. (ORCID:0000-0002-4374-3985), Bacigalupo A. (ORCID:0000-0002-9119-567X), Mohty, M., Terpos, E., Mateos, M. -V., Cavo, M., Lejniece, S., Beksac, M., Bekadja, M. A., Legiec, W., Dimopoulos, M., Stankovic, S., Duran, M. S., De Stefano, Valerio, Corso, A., Kochkareva, Y., Laane, E., Berthou, C., Salwender, H., Masliak, Z., Peceliunas, V., Willenbacher, W., Silva, J., Louw, V., Nemet, D., Borbenyi, Z., Abadi, U., Pedersen, R. S., Cernelc, P., Potamianou, A., Couturier, C., Feys, C., Thoret-Bauchet, F., Boccadoro, M., Bekadja, M., Hamladji, R. -M., Ali, H. A., Hamdi, S., Touhami, H., Mansour, N. S., Linkesch, W., Abildgaard, N., Hein, M., Eveillard, J. R., Yamani, A. E., Moreau, P., Sanhes, L., Lepeu, G., Laribi, K., Jourdan, E., Fitoussi, O., Allangba, O., Fleury, J., Escoffre, M., Benramdane, R., Cartron, G., Dine, G., Legouffe, E., Harich, H. -D., Illmer, T., Dorfel, S., Hannig, C. V., Koenigsmann, M., Prange-Krex, G., Tamm, I., Zeller, W., Maasberg, M., Schlag, R., Klausmann, M., Uhlig, J., Alkemper, B., Schutz, S., Tessen, H. -W., Mohr, B., Schmidt, P., Heinrich, B., Hebart, H., Seipelt, G., Zoeller, T., Heits, F., Muller-Naendrup, C., Hansen, R., Repp, R., Von Weikersthal, L. F., Schmits, R., Hessling, J., Krammer-Steiner, B., Janzen, V., Schauer, M., Gruner, M. W., Kisro, J., Denzlinger, C., Freier, W., Junghanss, C., Gorner, M., Laichinger, K., Ostermann, H., Durk, H., Hess, G., Reich, G., Matsouka, P., Pouli, A., Anagnostopoulos, A., Masszi, T., Ivanyi, J., Szomor, A., Nagler, A., Magen, H., Avivi, I., Quitt, M., Palumbo, A., Za, Tommaso, Vallisa, D., Foa, R., Bosi, A., Vacca, A., Lanza, F., Palazzo, G., Avvisati, G., Ferrara, F., Consoli, U., Cantonetti, M., Angelucci, E., Califano, C., Di Raimondo, F., Guarini, A., Musso, M., Pizzuti, M., Giuliani, N., Ardizzoia, A., Di Renzo, N., Gaidano, G., Gozzetti, A., Pitini, V., Farina, G., Centurioni, R., De Fabritiis, P., Iuliano, F., La Nasa, G., La Verde, G., Pane, F., Recine, U., La Targia, M., Mineo, G., Cangialosi, C., Fagnani, D., Federici, A., Romano, A., Specchia, G., Storti, Sergio, Bongarzoni, V., Bacigalupo, Andrea, Gobbi, M., Latte, G., Mannina, D., Capalbo, S., Jurgutis, M., Woszczyk, D., Holojda, J., Gornik, S., Pluta, A., Morawiec-Szymonik, E., Kyrcz-Krzemien, S., Homenda, W., Grosicki, S., Sulek, K., Lange, A., Kloczko, J., Starzak-Gwozdz, J., Hellmann, A., Komarnicki, M., Kuliczkowski, K., Viveiros, C., Goncalves, C., Esefyeva, N., Kaplanov, K., Volodicheva, E., Laricheva, E., Dergacheva, V., Chukavina, M., Volchenko, N., Nazarova, I., Anchukova, L., Ovanesova, E., Salogub, G., Magomedova, L., Kuznetsova, I., Osyunikhina, S., Serdyuk, O., Karyagina, E., Ivanova, V., Cernelc, S. P., Coetzee, C., Gunther, K., Moodley, D., Duran, S., Gutierrez, A. E., De Oteyza, J. P., Capote, F. J., Casanova, M., Sanchez, J. M., Rios-Herranz, E., Ibanez-Garcia, J., Herranz, M. J., Hernandez, B., Sanchez, S. S., Escalante, F., Carnicero, F., Lleonart, J. B., Gironella, M., Martinez, R., De La Guia, A. L., Palomera, L., Iglesias, R., Ramos, F. S., De La Serna, J., Sanchez, P. G., Vidal, J. B., Morfa, M. D., Beksac, T. -M., Vural, F., Aydin, Y., Unal, A., Goker, H., Bilgir, O., Guvenc, B., Turgut, M., Ozet, G. G., Ali, R., Kyselyova, M., Glushko, N., Vybyrana, R., Skrypnyk, I., Tretyak, N., Kharchevska, T., Dyagil, I., Popovs'Ka, T., Shimanskiy, V., Lysa, T., Oliynyk, H., Vilchevskaya, K., Kryachok, I., Popovych, Y., Romanyuk, N., Yushchenko, N., Kaplan, P., Rekhtman, G., Pylypenko, H., Kozlov, V., Drach, J., Harousseau, J. -L., Einsele, H., Goldschmidt, H., Facon, T., Michalet, M., Savchenko, V. G., De la Rubia, J., Cook, G., Mellqvist, U. -H., Ludwig, H., De Stefano V. (ORCID:0000-0002-5178-5827), Za T., Storti S. (ORCID:0000-0002-4374-3985), and Bacigalupo A. (ORCID:0000-0002-9119-567X)

Abstract

Multiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and

Published
2018

12. Post-translational deregulation of YAP1 is genetically controlled in rat liver cancer and determines the fate and stem-like behavior of the human disease

Author

Simile, M.M. (María M.), Latte, G. (Gavinella), Demartis, M.I. (María I.), Brozzetti, S. (Stefania), Calvisi, D.F. (Diego F.), Porcu, A. (Alberto), Feo, C.F. (Claudio F.), Seddaiu, M.A. (María A.), Daino, L. (Lucia), Berasain, C. (Carmen), Tomasi, M.L. (María L.), Avila, M.A. (Matías Antonio), Feo, F. (Francesco), and Pascale, R.M. (Rosa M.)

Subjects
Hepatocarcinogenesis, Progression, Yap targets, Stem cells, Gene expression profile, neoplasms, digestive system diseases
Abstract

Previous studies showed that YAP1 is over-expressed in hepatocellular carcinoma (HCC). Here we observed higher expression of Yap1/Ctgf axis in dysplastic nodules and HCC chemically-induced in F344 rats, genetically susceptible to hepatocarcinogenesis, than in lesions induced in resistant BN rats. In BN rats, highest increase in Yap1- tyr357, p73 phosphorylation and Caspase 3 cleavage occurred. In human HCCs with poorer prognosis (< 3 years survival after partial liver resection, HCCP), levels of YAP1, CTGF, 14–3–3, and TEAD proteins, and YAP1-14-3-3 and YAP1-TEAD complexes were higher than in HCCs with better outcome (> 3 years survival; HCCB). In the latter, higher levels of phosphorylated YAP1-ser127, YAP1-tyr357 and p73, YAP1 ubiquitination, and Caspase 3 cleavage occurred. Expression of stemness markers NANOG, OCT-3/4, and CD133 were highest in HCCP and correlated with YAP1 and YAP1-TEAD levels. In HepG2, Huh7, and Hep3B cells, forced YAP1 over-expression led to stem cell markers expression and increased cell viability, whereas inhibition of YAP1 expression by specific siRNA, or transfection of mutant YAP1 which does not bind to TEAD, induced opposite alterations. These changes were associated, in Huh7 cells transfected with YAP1 or YAP1 siRNA, with stimulation or inhibition of cell migration and invasivity, respectively. Furthermore, transcriptome analysis showed that YAP1 transfection in Huh7 cells induces over-expression of genes involved in tumor stemness. In conclusion, Yap1 post-translational modifications favoring its ubiquitination and apoptosis characterize HCC with better prognosis, whereas conditions favoring the formation of YAP1-TEAD complexes are associated with aggressiveness and acquisition of stemness features by HCC cells.

Published
2016

14. Long-term outcome of chronic myeloid leukemia patients treated frontline with imatinib

Author

Castagnetti, F, Gugliotta, G., Breccia, M., Stagno, F., Iurlo, A., Albano, F., Abruzzese, E., Martino, B., Levato, L., Intermesoli, T., Pregno, P., Rossi, G., Gherlinzoni, F., Leoni, P., Cavazzini, F., Venturi, C., Soverini, S., Testoni, N., Alimena, G., Cavo, M., Martinelli, G., Pane, F., Saglio, G., Rosti, G., Baccarani, M., on behalf of the GIMEMA CML Working Party (Lucarelli, G., Polimeno, G., Ladetto, M., Pini, M., Rupoli, S., Scortechini, A. R., Galieni, P., Bigazzi, C., Cantore, N., Palmieri, F., Specchia, G., Russo, Rossi., Rambaldi, A., Ferrari, M. L., Palandri, F., Luatti, S., Iacobucci, I., Bochicchio, M. T., Apolinari, M., Fogli, M., Cervello, I., Capucci, A., Giuliani, G., Malpignano, A., Girasoli, M., Angelucci, E., Usala, E., De Biasi, E., Tagariello, G., Sartori, R., Di Raimondo, F., Vigneri, P., Molica, S., Lentini, M., Lanza, F., Viganò, C., Grasso, M., Rapezzi, D., Cuneo, A., Ciccone, M., Bosi, A., Gozzini, A., Gobbi, M., Pierri, I., Chianese, R., De Blasio, A., Ciccone, F., Capochiani, E., Pelosini, M., Musolino, C., Russo, S., Cortelezzi, A., Luppi, M., Marasca, R., Pogliani, E. M., Gambacorti-Passerini, C., Luciano, L., Izzo, B., Ferrara, F., Annunziata, M., Mettivier, V., Sessa, U., Latte, G., Noli, D., Rege-Cambrin, G., Fava, C., Semenzato, G., Binotto, G., Fabbiano, F., Turri, D., Siragusa, S., Caracciolo, C., Musso, M., Porretto, F., Cazzola, M., Orlandi, E., Falini, B., Falzetti, F., Visani, G., Isidor, I., Di Bartolomeo, P., Di Lorenzo, R., Vallisa, D., Trabacch, I., Pizzuti, M., Zuffa, E., Salvucci, M., Ronco, F., Lelo, D., Merli, F., Avanzini, P., Tosi, P., Merli, A., Sica, S., Sorà, F., Latagliata, R., De Fabritiis, P., Trawiska, M., Amadori, S., Cantonetti, M., Majolino, I., Pacilli, L., Ronci, B., Cedrone, M., Mengarelli, A., Romano, A., Tafuri, A., Montefusc, O., Iuliano, F., Infusino, S., Dore, F., Fozza, C., Bocchia, M., Defina, M., Liberati, Am., Luzi, D., Boccadoro, M., Ferrero, D., Vitolo, U., Nicolosi, M., Gottardi, M., Calistri, E., Fanin, R., Tiribelli, M., Pizzolo, G., Bonifacio, M., Rodeghiero, F., Di Bona, E. )., Castagnetti, F, Gugliotta, G., Breccia, M., Stagno, F., Iurlo, A., Albano, F., Abruzzese, E., Martino, B., Levato, L., Intermesoli, T., Pregno, P., Rossi, G., Gherlinzoni, F., Leoni, P., Cavazzini, F., Venturi, C., Soverini, S., Testoni, N., Alimena, G., Cavo, M., Martinelli, G., Pane, F., Saglio, G., Rosti, G., Baccarani, M., and on behalf of the GIMEMA CML Working Party [, Palandri F.], Pane, Fabrizio, Gugliotta, G, Breccia, M, Stagno, F, Iurlo, A, Albano, F, Abruzzese, E, Martino, B, Levato, L, Intermesoli, T, Pregno, P, Rossi, G, Gherlinzoni, F, Leoni, P, Cavazzini, F, Venturi, C, Soverini, S, Testoni, N, Alimena, G, Cavo, M, Martinelli, G, Pane, F, Saglio, G, Rosti, G, Baccarani, M, and GAMBACORTI PASSERINI, C

Subjects
DIAGNOSED CHRONIC-PHASE, Oncology, Male, Cancer Research, Time Factors, bcr-abl, Fusion Proteins, bcr-abl, Antineoplastic Agent, Hematology, Anesthesiology and Pain Medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, 80 and over, Cumulative incidence, Young adult, Chronic, Aged, 80 and over, Leukemia, PATIENTS RECEIVING IMATINIB, CHRONIC MYELOGENOUS LEUKEMIA, TYROSINE KINASE INHIBITORS, BCR-ABL1 TRANSCRIPT LEVELS, EARLY MOLECULAR RESPONSE, CML WORKING PARTY, 3-YEAR FOLLOW-UP, EUROPEAN LEUKEMIANET, 400 MG, Myeloid leukemia, Middle Aged, Prognosis, Treatment Outcome, Retreatment, Imatinib Mesylate, Female, Tyrosine kinase, Human, medicine.drug, Adult, medicine.medical_specialty, Time Factor, Adolescent, Prognosi, Protein Kinase Inhibitor, Socio-culturale, Antineoplastic Agents, Treatment results, Follow-Up Studie, Young Adult, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Internal medicine, medicine, Humans, Protein Kinase Inhibitors, Aged, Antineoplastic Combined Chemotherapy Protocol, business.industry, Fusion Proteins, Imatinib, Follow-Up Studies, Surgery, Imatinib mesylate, BCR-ABL Positive, business, Myelogenous
Abstract

For almost 10 years imatinib has been the therapeutic standard of chronic myeloid leukemia. The introduction of other tyrosine kinase inhibitors (TKIs) raised a debate on treatment optimization. The debate is still heated: some studies have protocol restrictions or limited follow-up; in other studies, some relevant data are missing. The aim of this report is to provide a comprehensive, long-term, intention-to-treat, analysis of 559 newly diagnosed, chronic-phase, patients treated frontline with imatinib. With a minimum follow-up of 66 months, 65% of patients were still on imatinib, 19% were on alternative treatment, 12% died and 4% were lost to follow-up. The prognostic value of BCR-ABL1 ratio at 3 months (⩽10% in 81% of patients) was confirmed. The prognostic value of complete cytogenetic response and major molecular response at 1 year was confirmed. The 6-year overall survival was 89%, but as 50% of deaths occurred in remission, the 6-year cumulative incidence of leukemia-related death was 5%. The long-term outcome of first-line imatinib was excellent, also because of second-line treatment with other TKIs, but all responses and outcomes were inferior in high-risk patients, suggesting that to optimize treatment results, a specific risk-adapted treatment is needed for such patients.

Published
2015

19. Differences among young adults, adults and elderly chronic myeloid leukemia patients

Author

Castagnetti, F, Gugliotta, G, Baccarani, M, Breccia, M, Specchia, G, Levato, L, Abruzzese, E, Rossi, G, Iurlo, A, Martino, B, Pregno, P, Stagno, F, Cuneo, A, Bonifacio, M, Gobbi, M, Russo, D, Gozzini, A, Tiribelli, M, De Vivo, A, Alimena, G, Cavo, M, Martinelli, G, Pane, F, Saglio, G, Rosti, G, Salvi, F, Pini, M, Leoni, P, Rupoli, S, Galieni, P, Bigazzi, C, Cantore, N, Palmieri, F, Albano, F, Russo Rossi, A, Rambaldi, A, Intermesoli, T, Palandri, F, Testoni, N, Luatti, S, Soverini, S, Iacobucci, I, Bochicchio, M, Apolinari, M, Fogli, M, Cervello, I, Capucci, A, Malagola, M, Malpignano, A, Girasoli, M, Angelucci, E, Usala, E, Storti, S, De Biasi, E, Tagariello, G, Sartori, R, Di Raimondo, F, Vigneri, P, Impera, S, Molica, S, Lanza, F, Viganò, C, Grasso, M, Rapezzi, D, Cavazzini, F, Bosi, A, Santini, V, Capalbo, S, Spinosa, G, Pierri, I, Bergamaschi, M, Carella, A, Bacigalupo, A, De Blasio, A, Ciccone, F, Di Renzo, N, Musolino, C, Russo, S, Cortelezzi, A, Morra, E, Pungolino, E, Luppi, M, Marasca, R, Pogliani, E, GAMBACORTI PASSERINI, C, Luciano, L, Ferrara, F, Annunziata, M, Latte, G, Noli, D, Rege Cambrin, G, Fava, C, Semenzato, G, Binotto, G, Fabbiano, F, Turri, D, Siragusa, S, Caracciolo, C, Musso, M, Porretto, F, Aversa, F, Crugnola, M, Cazzola, M, Orlandi, E, Falini, B, Falzetti, F, Visani, G, Isidori, A, Fioritoni, G, Di Lorenzo, R, Vallisa, D, Trabacchi, E, Petrini, M, Galimberti, S, Pizzuti, M, Zaccaria, A, Salvucci, M, Ronco, F, Ielo, D, Merli, F, Avanzini, P, Tosi, P, Merli, A, Musto, P, De Stefano, V, Sica, S, Latagliata, R, De Fabritiis, P, Trawiska, M, Majolino, I, Pacilli, L, Ronci, B, Cedrone, M, Petti, M, Pisani, F, Tafuri, A, Montefusco, E, Iuliano, F, Dore, F, Pardini, S, Bocchia, M, Defina, M, Liberati, A, Luzzi, D, Boccadoro, M, Ferrero, D, Vitolo, U, Gherlinzoni, F, Calistri, E, Fanin, R, Pizzolo, G, Meneghini, V, Rodighiero, F, D'Emilio, A, GAMBACORTI PASSERINI, CARLO, D'Emilio, A., Castagnetti, F, Gugliotta, G, Baccarani, M, Breccia, M, Specchia, G, Levato, L, Abruzzese, E, Rossi, G, Iurlo, A, Martino, B, Pregno, P, Stagno, F, Cuneo, A, Bonifacio, M, Gobbi, M, Russo, D, Gozzini, A, Tiribelli, M, De Vivo, A, Alimena, G, Cavo, M, Martinelli, G, Pane, F, Saglio, G, Rosti, G, Salvi, F, Pini, M, Leoni, P, Rupoli, S, Galieni, P, Bigazzi, C, Cantore, N, Palmieri, F, Albano, F, Russo Rossi, A, Rambaldi, A, Intermesoli, T, Palandri, F, Testoni, N, Luatti, S, Soverini, S, Iacobucci, I, Bochicchio, M, Apolinari, M, Fogli, M, Cervello, I, Capucci, A, Malagola, M, Malpignano, A, Girasoli, M, Angelucci, E, Usala, E, Storti, S, De Biasi, E, Tagariello, G, Sartori, R, Di Raimondo, F, Vigneri, P, Impera, S, Molica, S, Lanza, F, Viganò, C, Grasso, M, Rapezzi, D, Cavazzini, F, Bosi, A, Santini, V, Capalbo, S, Spinosa, G, Pierri, I, Bergamaschi, M, Carella, A, Bacigalupo, A, De Blasio, A, Ciccone, F, Di Renzo, N, Musolino, C, Russo, S, Cortelezzi, A, Morra, E, Pungolino, E, Luppi, M, Marasca, R, Pogliani, E, GAMBACORTI PASSERINI, C, Luciano, L, Ferrara, F, Annunziata, M, Latte, G, Noli, D, Rege Cambrin, G, Fava, C, Semenzato, G, Binotto, G, Fabbiano, F, Turri, D, Siragusa, S, Caracciolo, C, Musso, M, Porretto, F, Aversa, F, Crugnola, M, Cazzola, M, Orlandi, E, Falini, B, Falzetti, F, Visani, G, Isidori, A, Fioritoni, G, Di Lorenzo, R, Vallisa, D, Trabacchi, E, Petrini, M, Galimberti, S, Pizzuti, M, Zaccaria, A, Salvucci, M, Ronco, F, Ielo, D, Merli, F, Avanzini, P, Tosi, P, Merli, A, Musto, P, De Stefano, V, Sica, S, Latagliata, R, De Fabritiis, P, Trawiska, M, Majolino, I, Pacilli, L, Ronci, B, Cedrone, M, Petti, M, Pisani, F, Tafuri, A, Montefusco, E, Iuliano, F, Dore, F, Pardini, S, Bocchia, M, Defina, M, Liberati, A, Luzzi, D, Boccadoro, M, Ferrero, D, Vitolo, U, Gherlinzoni, F, Calistri, E, Fanin, R, Pizzolo, G, Meneghini, V, Rodighiero, F, D'Emilio, A, GAMBACORTI PASSERINI, CARLO, and D'Emilio, A.

Abstract

Background: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. Patients and methods: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CMLWP over a 40-year period. Results: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0 cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011). Conclusions: The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome.

Published
2015

22. Deferasirox for Transfusion-Dependent Patients with Myelodysplastic Syndromes: Safety, Efficacy, and Beyond (GIMEMA MDS0306 Trial)

Author

Angelucci, E, Santini, V, Tucci, Aad, Quaresmini, G, Finelli, C, Volpe, A, Quarta, G, Rivellini, F, Sanpaolo, G, Cilloni, D, Salvi, F, Caocci, G, Molteni, A, Vallisa, D, Voso, Maria Teresa, Fenu, S, Borin, L, Latte, G, Alimena, G, Storti, Sergio, Piciocchi, A, Fazi, P, Vignetti, M, Tura, S., Storti, S (ORCID:0000-0002-4374-3985), Angelucci, E, Santini, V, Tucci, Aad, Quaresmini, G, Finelli, C, Volpe, A, Quarta, G, Rivellini, F, Sanpaolo, G, Cilloni, D, Salvi, F, Caocci, G, Molteni, A, Vallisa, D, Voso, Maria Teresa, Fenu, S, Borin, L, Latte, G, Alimena, G, Storti, Sergio, Piciocchi, A, Fazi, P, Vignetti, M, Tura, S., and Storti, S (ORCID:0000-0002-4374-3985)

Abstract

In the absence of randomized, controlled trial data to support iron chelation therapy in transfusion-dependent patients with myelodysplastic syndromes (MDS), continued evidence from large prospective clinical trials evaluating the efficacy and safety of iron chelation therapy in this patient population is warranted.

Published
2014

23. Underserved populations and bacterial and protozoal sexually transmitted infections: a lost health-care opportunity.

Author

FIORE, V., LATTE, G., MADEDDU, G., GALLERI, G., ROCCHITTA, G., NUVOLI, S., CALVISI, D., BAGELLA, P., MANETTI, R., SERRA, P. A., SPANU, A., and BABUDIERI, S.

Abstract

OBJECTIVE: The purpose of our review is an update about the burden of sexually transmitted infections (STIs) among various types of underserved populations, such as migrants, substance abusers, homeless and incarcerated inmates. First-line test and treatment based on the latest available evidence according to the revised guidelines of Centers for Disease Control and Prevention have also been considered. MATERIALS AND METHODS: We performed a comprehensive research using scientific databases such as Medline and Pubmed, followed by a review of citations and reference list. A consultation with other experts in the management of the various subpopulations was also conducted. RESULTS: Health-care is often influenced by social determinants, which play a vital role in the diffusion of STIs. The consequence is a socio-economical and ethnic disparity in the rate of STIs. Early screening and treatment of STIs should be implemented in clinical practice, starting from marginalized social groups, which are the most affected by this health problem. CONCLUSIONS: In the literature, there are very few papers containing information on STIs prevalence in various types of underserved populations, such as migrants, substance abusers, homeless and incarcerated inmates. The availability of more accurate epidemiological data is needed. In these groups, the most relevant barrier is the lower perception of health-care need, with an underestimation of risk and symptoms of STIs, causing a retard of diagnosis and healthcare provision and use. For these populations, targeted interventions are needed, particularly on unaware people, responsible for most STIs transmissions. [ABSTRACT FROM AUTHOR]

Published
2017

25. EPA-1118 - Knowledge of the illness and its relations with quality of life, social functioning, cognitive performances, and adherence in psychotic patients: Toward effectiveness-focused interventions

Author

Avvisati, L., primary, Latte, G., additional, Gilardi, V., additional, Giordano, S., additional, Balletta, R., additional, Prinzivalli, E., additional, Buonaguro, E.F., additional, Elce, C., additional, Rossi, R., additional, Formato, M.V., additional, Acampora, R., additional, Avagliano, C., additional, Fico, G., additional, Mazzola, G., additional, Tomasetti, C., additional, De Bartolomeis, A., additional, and Iasevoli, F., additional

Published
2014
Full Text
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28. Deregulation of DNA-dependent protein kinase catalytic subunit contributes to human hepatocarcinogenesis development and has a putative prognostic value

Author

Evert, M, primary, Frau, M, additional, Tomasi, M L, additional, Latte, G, additional, Simile, M M, additional, Seddaiu, M A, additional, Zimmermann, A, additional, Ladu, S, additional, Staniscia, T, additional, Brozzetti, S, additional, Solinas, G, additional, Dombrowski, F, additional, Feo, F, additional, Pascale, R M, additional, and Calvisi, D F, additional

Published
2013
Full Text
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29. 2251 – Cortical and subcortical gene-expression imaging by different n-methyl-daspartate receptor (nmda-r) antagonists at glutammatergic synapses: implications for dopamine-glutamate interplay in psychoses

Author

Avvisati, L., primary, Rossi, R., additional, Latte, G., additional, Buonaguro, E.F., additional, Eramo, A., additional, Marmo, F., additional, Tomasetti, C., additional, Sarappa, C., additional, Iasevoli, F., additional, and de Bartolomeis, A., additional

Published
2013
Full Text
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37. Temozolomide as salvage treatment in primary brain lymphomas

Author

Reni, M, primary, Zaja, F, additional, Mason, W, additional, Perry, J, additional, Mazza, E, additional, Spina, M, additional, Bordonaro, R, additional, Ilariucci, F, additional, Faedi, M, additional, Corazzelli, G, additional, Manno, P, additional, Franceschi, E, additional, Pace, A, additional, Candela, M, additional, Abbadessa, A, additional, Stelitano, C, additional, Latte, G, additional, and Ferreri, A J M, additional

Published
2007
Full Text
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41. HIGH DOSE SEQUENTIALCHEMOTHERAPY WITH RITUXIMAB AND ASCT AS FIRST LINE THERAPY IN ADULT MCL PATIENTS: CLINICAL AND MOLECULARRESPONSE OF THE MCL0208 TRIAL, A FIL STUDY

Author

Vitolo, U., Federico, M., Chilosi, M., Zamo, A., Paulli, M., Novero, D., Cabras, M. G., Latte, G., Michieli, M., Liberati, A. M., Molinari, A., Gomes, M., Gobbi, M., Luca Arcaini, Gotti, M., Rusconi, C., Cavallo, F., Balzarotti, M., Zinzani, P. L., Re, A., Rossi, G., Chiappella, A., Di Rocco, A., Mian, M., Evangelista, A., Ciccone, G., Ferrero, S., Ladetto, M., Martelli, M., and Cortelazzo, S.

42. Activation of the aryl hydrocarbon receptor and risk of lymphoma subtypes

Author

Sanna, S., Satta, G., Padoan, M., Piro, S., Gambelunghe, A., Lucia Miligi, Ferri, G. M., Magnani, C., Muzi, G., Rigacci, L., Cabras, M. G., Angelucci, E., Latte, G. C., Gabbas, A., Ennas, M. G., and Cocco, P.

Subjects
dual luciferase assay, hemic and lymphatic diseases, case-control study, Original Article, lymphoma, Aryl hydrocarbon receptor, molecular epidemiology
Abstract

The aryl hydrocarbon receptor (AhR) is a transcription factor implicated in several pathways known to be relevant in lymphomagenesis. Aim of our study was to explore the link between AhR activation and risk of lymphoma subtypes. We used a Dual-Luciferase Assay® and a luminometer to detect the activation of the luciferase gene, in HepG2 cells transfected with a specific reporter systems, by a 50 ml serum aliquot of cases of diffuse large B cell lymphoma (N = 108), follicular lymphoma (N = 85), chronic lymphocytic leukemia (N = 72), multiple myeloma (N = 80), and Hodgkin lymphoma (N = 94) and 357 controls who participated in the multicentre Italian study on gene-environment interactions in lymphoma etiology (ItGxE). Risk of each lymphoma subtype associated with AhR activation was calculated with polytomous logistic regression adjusting by age, gender, and study centre. The overall prevalence of AhR activation ranged 13.9-23.6% by subtype, and it varied by study area (8-39%). Risk associated with AhR activation was moderately elevated for follicular lymphoma (OR = 1.56, 95% CI 0.86, 2.80) and chronic lymphocytic leukemia (OR = 1.56, 95% CI 0.83, 2.96). Despite our inconclusive findings about the association with risk of lymphoma subtypes, we showed that the Dual-Luciferase Assay can be reliably and easily applied in population-based studies to detect AhR activation.

43. Underserved populations and bacterial and protozoal sexually transmitted infections: a lost health-care opportunity

Author

Fiore, V., Latte, G., Giordano MADEDDU, Galleri, G., Rocchitta, G., Nuvoli, S., Calvisi, D., Bagella, P., Manetti, R., Serra, P. A., Spanu, A., and Babudieri, S.

Subjects
Male, Transients and Migrants, Databases, Factual, Substance-Related Disorders, Sexual Behavior, Ill-Housed Persons, Sexually Transmitted Diseases, Humans, Female, Delivery of Health Care, Anti-Bacterial Agents
Abstract

The purpose of our review is an update about the burden of sexually transmitted infections (STIs) among various types of underserved populations, such as migrants, substance abusers, homeless and incarcerated inmates. First-line test and treatment based on the latest available evidence according to the revised guidelines of Centers for Disease Control and Prevention have also been considered.We performed a comprehensive research using scientific databases such as Medline and Pubmed, followed by a review of citations and reference list. A consultation with other experts in the management of the various subpopulations was also conducted.Health-care is often influenced by social determinants, which play a vital role in the diffusion of STIs. The consequence is a socio-economical and ethnic disparity in the rate of STIs. Early screening and treatment of STIs should be implemented in clinical practice, starting from marginalized social groups, which are the most affected by this health problem.In the literature, there are very few papers containing information on STIs prevalence in various types of underserved populations, such as migrants, substance abusers, homeless and incarcerated inmates. The availability of more accurate epidemiological data is needed. In these groups, the most relevant barrier is the lower perception of health-care need, with an underestimation of risk and symptoms of STIs, causing a retard of diagnosis and health-care provision and use. For these populations, targeted interventions are needed, particularly on unaware people, responsible for most STIs transmissions.

44. Differences among young adults, adults and elderly chronic myeloid leukemia patients

Author

D. Ielo, Mario Cazzola, A. De Vivo, Mario Petrini, G. Fioritoni, Simona Sica, Fausto Castagnetti, B. Falini, Miriam Fogli, Agostino Cortelezzi, C. Viganò, Giuliana Alimena, Maurizio Musso, G. Spinosa, Flavia Salvi, Giancarlo Latte, Michele Pizzuti, Nicola Cantore, D. Luzzi, B. Ronci, Francesco Merli, Mario Boccadoro, Diamante Turri, Monica Bocchia, Patrizia Tosi, A. M. Carella, Simona Luatti, G. Semenzato, Mariella Grasso, Nicoletta Testoni, Giovanni Martinelli, Ester Pungolino, Giuseppe Tagariello, A. Russo Rossi, Simona Soverini, Francesca Ronco, Franco Iuliano, Giovanni Rosti, Alberto Bosi, Tamara Intermesoli, Dario Ferrero, Sara Galimberti, Giovanna Rege-Cambrin, Ferdinando Porretto, Sabina Russo, Roberto Latagliata, Pellegrino Musto, E. Morra, Agostino Tafuri, Franca Falzetti, Francesco Cavazzini, P. Galieni, Marzia Salvucci, F. Rodighiero, Stefana Impera, Fausto Dore, P. De Fabritiis, V. Meneghini, Elisabetta Calistri, Paolo Vigneri, Ivana Pierri, Michele Cavo, Massimo Pini, Fabrizio Ciccone, Domenico Russo, E Trabacchi, Franco Gherlinzoni, Michele Baccarani, Ilaria Iacobucci, Roberto Sartori, Paolo Avanzini, D. Noli, Roberto Marasca, Simonetta Pardini, A. Malpignano, Maria Concetta Petti, Bruno Martino, M. Bergamaschi, Giovanni Pizzolo, Valeria Santini, E Orlandi, Catia Bigazzi, Serena Rupoli, Giuseppe Saglio, I. Cervello, Clementina Caracciolo, Anna Merli, R. Di Lorenzo, Enrico Pogliani, Francesco Lanza, Mariella Girasoli, M. Apolinari, Caterina Musolino, Francesco Fabbiano, D. Vallisa, Mario Annunziata, Gabriele Gugliotta, V. De Stefano, Ignazio Majolino, Sergio Storti, P. Leoni, Adele Capucci, Massimo Breccia, Alessandro Isidori, Carmen Fava, Gianni Binotto, Carlo Gambacorti-Passerini, L. Pacilli, Mario Tiribelli, Luciano Levato, Felicetto Ferrara, N. Di Renzo, Anna D'Emilio, Francesco Pisani, Fabio Stagno, Monica Crugnola, M. Trawiska, Patrizia Pregno, Marzia Defina, Stefano Molica, Mario Luppi, Michele Malagola, Davide Rapezzi, A. M. Liberati, E. De Biasi, A. Iurlo, Umberto Vitolo, Silvana Capalbo, Maria Teresa Bochicchio, F. Di Raimondo, Franco Aversa, Giuseppe Visani, Fausto Palmieri, Alessandro Rambaldi, Sergio Siragusa, Massimiliano Bonifacio, Luigiana Luciano, Giorgina Specchia, Elisabetta Abruzzese, A. De Blasio, Francesco Albano, Antonio Cuneo, Emilio Usala, Alfonso Zaccaria, R Fanin, Francesca Palandri, Fabrizio Pane, Enrico Montefusco, A. Gozzini, Giulio Rossi, Emanuele Angelucci, A. Bacigalupo, Marco Gobbi, Michele Cedrone, Castagnetti, F., Gugliotta, G., Baccarani, M., Breccia, M., Specchia, G., Levato, L., Abruzzese, E., Rossi, G., Iurlo, A., Martino, B., Pregno, P., Stagno, F., Cuneo, A., Bonifacio, M., Gobbi, M., Russo, D., Gozzini, A., Tiribelli, M., de Vivo, A., Alimena, G., Cavo, M., Martinelli, G., Pane, F., Saglio, G., Rosti, G., on behalf of the, GIMEMA CML Working Party [.., Palandri, F., Testoni, N., Luatti, S., Soverini, S., Iacobucci, I., Bochicchio, M.T., Apolinari, M., Fogli, M., Cervello, I., ]., Castagnetti, Fausto, De Vivo, A., Pane, Fabrizio, Salvi, F., Pini, M., Leoni, P., Rupoli, S., Galieni, P., Bigazzi, C., Cantore, N., Palmieri, F., Albano, F., Russo Rossi, A., Rambaldi, A., Intermesoli, T., Bochicchio, M. T., Capucci, A., Malagola, M., Malpignano, A., Girasoli, M., Angelucci, E., Usala, E., Storti, S., De Biasi, E., Tagariello, G., Sartori, R., Di Raimondo, F., Vigneri, P., Impera, S., Molica, S., Lanza, F., Viganò, C., Grasso, M., Rapezzi, D., Cavazzini, F., Bosi, A., Santini, V., Capalbo, S. F., Spinosa, G., Pierri, I., Bergamaschi, M., Carella, A. M., Bacigalupo, A., De Blasio, A., Ciccone, F., Di Renzo, N., Musolino, C., Russo, S., Cortelezzi, A., Morra, E., Pungolino, E. M., Luppi, M., Marasca, R., Pogliani, E. M., Gambacorti Passerini, C., Luciano, L., Ferrara, F., Annunziata, M., Latte, G., Noli, D., Rege Cambrin, G., Fava, C., Semenzato, G., Binotto, G., Fabbiano, F., Turri, D., Siragusa, S., Caracciolo, C., Musso, M., Porretto, F., Aversa, F., Crugnola, M., Cazzola, M., Orlandi, E., Falini, B., Falzetti, F., Visani, G., Isidori, A., Fioritoni, G., Di Lorenzo, R., Vallisa, D., Trabacchi, E., Petrini, M., Galimberti, S., Pizzuti, M., Zaccaria, A., Salvucci, M., Ronco, F., Ielo, D., Merli, F., Avanzini, P., Tosi, P., Merli, A., Musto, P., De Stefano, V., Sica, S., Latagliata, R., De Fabritiis, P., Trawiska, M., Majolino, I., Pacilli, L., Ronci, B., Cedrone, M., Petti, M. C., Pisani, F., Tafuri, A., Montefusco, E., Iuliano, F., Dore, F., Pardini, S., Bocchia, M., Defina, M., Liberati, A. M., Luzzi, D., Boccadoro, M., Ferrero, D., Vitolo, U., Gherlinzoni, F., Calistri, E., Fanin, R., Pizzolo, G., Meneghini, V., Rodighiero, F., D'Emilio, A., Castagnetti, F, Gugliotta, G, Baccarani, M, Breccia, M, Specchia, G, Levato, L, Abruzzese, E, Rossi, G, Iurlo, A, Martino, B, Pregno, P, Stagno, F, Cuneo, A, Bonifacio, M, Gobbi, M, Russo, D, Gozzini, A, Tiribelli, M, De Vivo, A, Alimena, G, Cavo, M, Martinelli, G, Pane, F, Saglio, G, Rosti, G, Salvi, F, Pini, M, Leoni, P, Rupoli, S, Galieni, P, Bigazzi, C, Cantore, N, Palmieri, F, Albano, F, Russo Rossi, A, Rambaldi, A, Intermesoli, T, Palandri, F, Testoni, N, Luatti, S, Soverini, S, Iacobucci, I, Bochicchio, M, Apolinari, M, Fogli, M, Cervello, I, Capucci, A, Malagola, M, Malpignano, A, Girasoli, M, Angelucci, E, Usala, E, Storti, S, De Biasi, E, Tagariello, G, Sartori, R, Di Raimondo, F, Vigneri, P, Impera, S, Molica, S, Lanza, F, Viganò, C, Grasso, M, Rapezzi, D, Cavazzini, F, Bosi, A, Santini, V, Capalbo, S, Spinosa, G, Pierri, I, Bergamaschi, M, Carella, A, Bacigalupo, A, De Blasio, A, Ciccone, F, Di Renzo, N, Musolino, C, Russo, S, Cortelezzi, A, Morra, E, Pungolino, E, Luppi, M, Marasca, R, Pogliani, E, GAMBACORTI PASSERINI, C, Luciano, L, Ferrara, F, Annunziata, M, Latte, G, Noli, D, Rege Cambrin, G, Fava, C, Semenzato, G, Binotto, G, Fabbiano, F, Turri, D, Siragusa, S, Caracciolo, C, Musso, M, Porretto, F, Aversa, F, Crugnola, M, Cazzola, M, Orlandi, E, Falini, B, Falzetti, F, Visani, G, Isidori, A, Fioritoni, G, Di Lorenzo, R, Vallisa, D, Trabacchi, E, Petrini, M, Galimberti, S, Pizzuti, M, Zaccaria, A, Salvucci, M, Ronco, F, Ielo, D, Merli, F, Avanzini, P, Tosi, P, Merli, A, Musto, P, De Stefano, V, Sica, S, Latagliata, R, De Fabritiis, P, Trawiska, M, Majolino, I, Pacilli, L, Ronci, B, Cedrone, M, Petti, M, Pisani, F, Tafuri, A, Montefusco, E, Iuliano, F, Dore, F, Pardini, S, Bocchia, M, Defina, M, Liberati, A, Luzzi, D, Boccadoro, M, Ferrero, D, Vitolo, U, Gherlinzoni, F, Calistri, E, Fanin, R, Pizzolo, G, Meneghini, V, Rodighiero, F, and D'Emilio, A

Subjects
Male, Pediatrics, Host response, BCR-ABL, Chronic myeloid leukemia, Prognosis, Tyrosine kinase inhibitors, Young adults, Adult, Age Factors, Aged, Aged, 80 and over, Antineoplastic Agents, Female, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Middle Aged, Prospective Studies, Protein Kinase Inhibitors, Protein-Tyrosine Kinases, Spleen, Splenomegaly, Young Adult, Oncology, Hematology, Tyrosine kinase inhibitor, Disease, Antineoplastic Agent, Tyrosin kinase inhibitor, Protein-Tyrosine Kinase, hemic and lymphatic diseases, 80 and over, Age Factor, Young adult, Chronic, Leukemia, Incidence (epidemiology), Myeloid leukemia, bcr-abl1, chronic myeloid leukemia, prognosis, tyrosine kinase inhibitors, young adults, Human, medicine.medical_specialty, Prognosi, Protein Kinase Inhibitor, NO, medicine, Adult patients, business.industry, medicine.disease, Clinical trial, Prospective Studie, Medicine (all), Immunology, BCR-ABL Positive, BCR-ABL, chronic myeloid leukemia, prognosis, tyrosine kinase inhibitors, young adults, business, Myelogenous
Abstract

BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0 cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011). CONCLUSIONS: The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome. CLINICAL TRIAL NUMBERS: NCT00510926, NCT00514488, NCT00769327, NCT00481052. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Published
2015

45. Modulation of glutamatergic functional connectivity by a prototypical antipsychotic: translational inference from a postsynaptic density Immediate-Early Gene-based network analysis

Author

Federica Marmo, Andrea de Bartolomeis, Gianmarco Latte, Giuseppe Giordano, Simona Signoriello, Elisabetta F. Buonaguro, Licia Vellucci, Felice Iasevoli, Camilla Avagliano, Annarita Barone, Carmine Tomasetti, Barone, A., Signoriello, S., Latte, G., Vellucci, L., Giordano, G., Avagliano, C., Buonaguro, E. F., Marmo, F., Tomasetti, C., Iasevoli, F., and de Bartolomeis, A.

Subjects
Male, Cingulate cortex, Homer1, medicine.medical_treatment, HOMER1, Brain network analysi, Biology, Nucleus accumbens, insula, haloperidol, Rats, Sprague-Dawley, Neural Pathway, 03 medical and health sciences, Behavioral Neuroscience, Glutamatergic, 0302 clinical medicine, Neural Pathways, Haloperidol, medicine, Animals, Gene Regulatory Networks, Antipsychotic, Genes, Immediate-Early, In Situ Hybridization, brain network analysis, post-synaptic density, schizophrenia, 030304 developmental biology, 0303 health sciences, Gene Regulatory Network, Neuronal Plasticity, Animal, Brain, Synapse, Rats, Antipsychotic Agent, Receptors, Glutamate, Synapses, Rat, Nerve Net, Transcriptome, Insula, Neuroscience, Postsynaptic density, 030217 neurology & neurosurgery, Antipsychotic Agents, medicine.drug
Abstract

Background Although extensively studied, the effect of antipsychotics is not completely understood at a network level. We tested the hypothesis that acute administration of haloperidol would modulate functional connectivity of brain regions relevant to schizophrenia pathophysiology. To assess putative changes in brain network properties and regional interactivity, we studied the expression of Homer1a, an Immediate Early Gene (IEG) demonstrated to be induced by antipsychotic administration and coding for a protein involved in glutamatergic synapses remodeling. Methods Sprague-Dawley rats (n = 26) assigned to vehicle (VEH; NaCl 0.9%) or haloperidol (HAL; 0.8 mg/kg) were included in the network analysis. Homer1a mRNA induction was evaluated by in situ hybridization. Signal intensity analysis was performed in 33 Regions of Interest (ROIs) in the cortex, the caudate putamen, and the nucleus accumbens. A signal correlation analysis was performed, computing all possible pairwise Pearson correlations among ROIs in the two groups. Two networks were generated for HAL and VEH groups, and their properties and topography were explored. Results VEH and HAL networks showed qualitative differences in global efficiency and clustering coefficient. The HAL network showed enhanced interactivity between cortical and striatal regions, and within caudate putamen subdivisions. On the other hand, it exhibited reduced inter-correlations between cingulate cortex and anterior insula and caudate putamen and nucleus accumbens. Moreover, haloperidol was able to modulate centrality of crucial functional hubs. These preclinical results corroborate and expand the clinical evidence that antipsychotics may modulate specific brain network properties and disease-related circuits’ interactivity.

Published
2021

46. Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study

Author

Mohamad Mohty, Evangelos Terpos, Maria-Victoria Mateos, Michele Cavo, Sandra Lejniece, Meral Beksac, Mohamed Amine Bekadja, Wojciech Legiec, Meletios Dimopoulos, Svetlana Stankovic, Maria Soledad Durán, Valerio De Stefano, Alessandro Corso, Yulia Kochkareva, Edward Laane, Christian Berthou, Hans Salwender, Zvenyslava Masliak, Valdas Pečeliūnas, Wolfgang Willenbacher, João Silva, Vernon Louw, Damir Nemet, Zita Borbényi, Uri Abadi, Robert Schou Pedersen, Peter Černelč, Anna Potamianou, Catherine Couturier, Caroline Feys, Florence Thoret-Bauchet, Mario Boccadoro, Mohamed Bekadja, Rose-Marie Hamladji, Hocine Ait Ali, Selma Hamdi, Hadj Touhami, Nourredine Sidi Mansour, Werner Linkesch, Robert Shou Pedersen, Niels Abildgaard, Marju Hein, Jean Richard Eveillard, Abderrazak el Yamani, Philippe Moreau, Laurence Sanhes, Gérard Lepeu, Kamel Laribi, Eric Jourdan, Olivier Fitoussi, Olivier Allangba, Joël Fleury, Martine Escoffre, Riad Benramdane, Guillaume Cartron, Gérard Dine, Eric Legouffe, Hanns-Detlev Harich, Thomas Illmer, Steffen Dörfel, Carla Verena Hannig, Michael Koenigsmann, Gabriele Prange-Krex, Ingo Tamm, Wolfgang Zeller, Michael Maasberg, Rudolf Schlag, Martine Klausmann, Jens Uhlig, Burkhard Alkemper, Stefan Schütz, Hans-Werner Tessen, Benno Mohr, Peter Schmidt, Bernhard Heinrich, Holger Hebart, Gernot Seipelt, Thomas Zoeller, Frank Heits, Clemens Müller-Naendrup, Richard Hansen, Roland Repp, Ludwig Fischer Von Weikersthal, Rudolf Schmits, Jörg Heßling, B. Krammer-Steiner, Viktor Janzen, Michael Schauer, Marcus W. Grüner, Jens Kisro, Claudio Denzlinger, Werner Freier, Christian Junghanss, Martin Görner, Katharina Laichinger, Helmut Ostermann, Heinz Dürk, Georg Hess, Gernot Reich, Panagiota Matsouka, Anastasia Pouli, Achilles Anagnostopoulos, Tamas Masszi, Janos Ivanyi, Arpad Szomor, Arnon Nagler, Hila Magen, Irit Avivi, Miriam Quitt, Antonio Palumbo, Tommaso Za, Daniele Vallisa, Roberto Foa, Alberto Bosi, Angelo Vacca, Francesco Lanza, Giulia Palazzo, Giuseppe Avvisati, Felicetto Ferrara, Ugo Consoli, Maria Cantonetti, Emanuele Angelucci, Catello Califano, Francesco Di Raimondo, Attilio Guarini, Maurizio Musso, Michele Pizzuti, Nicola Giuliani, Antonio Ardizzoia, Nicola Di Renzo, Gianluca Gaidano, Alessandro Gozzetti, Vincenzo Pitini, Gabriella Farina, Riccardo Centurioni, Paolo De Fabritiis, Francesco Iuliano, Giorgio La Nasa, Giacinto La Verde, Fabrizio Pane, Umberto Recine, Maria La Targia, Giuseppe Mineo, Clotilde Cangialosi, Daniele Fagnani, Augusto Federici, Atelda Romano, Giorgina Specchia, Sergio Storti, Velia Bongarzoni, Andrea Bacigalupo, Marco Gobbi, Giancarlo Latte, Donato Mannina, Silvana Capalbo, Mindaugas Jurgutis, Dariusz Woszczyk, Jadwiga Hołojda, Slawomir Gornik, Andrzej Pluta, Elzbieta Morawiec-Szymonik, Slawomira Kyrcz-Krzemien, Wojciech Homenda, Sebastian Grosicki, Kazimierz Sulek, Andrzej Lange, Janusz Kloczko, Jolanta Starzak-Gwozdz, Andrzej Hellmann, Mieczyslaw Komarnicki, Kazimierz Kuliczkowski, Carolina Viveiros, Cristina Gonçalves, Natalia Esefyeva, Julia Kochkareva, Kamil Kaplanov, Elena Volodicheva, Elena Laricheva, Valentina Dergacheva, Marina Chukavina, Natalia Volchenko, Irina Nazarova, Ludmila Anchukova, Elena Ovanesova, Taras Gritsenko, Galina Salogub, Ludmila Magomedova, Irina Kuznetsova, Svetlana Osyunikhina, Olga Serdyuk, Elena Karyagina, Valentina Ivanova, Slovenia Peter Černelč, Corlia Coetzee, Karen Gunther, Dhayanithi Moodley, Soledad Duran, Asunción Echeveste Gutiérrez, Jaime Perez De Oteyza, Francisco Javier Capote, Maria Casanova, Jesus Martin Sanchez, Eduardo Rios-Herranz, Jeronima Ibañez-Garcia, Maria Jose Herranz, Belen Hernandez, Sara Sanchez Sanchez, Fernando Escalante, Fernando Carnicero, Joan Bargay Lleonart, Mercedes Gironella, Rafael Martínez, Ana Lopez De La Guia, Luis Palomera, Rebeca Iglesias, Fernando Solano Ramos, Javier De La Serna, Pedro Garcia Sanchez, Juan Besalduch Vidal, Miguel Diaz Morfa, Turkey – Meral Beksac, Filiz Vural, Yildiz Aydin, Ali Unal, Hakan Goker, Oktay Bilgir, Birol Guvenc, Mehmet Turgut, Gulsum Gulistan Ozet, Ridvan Ali, Maryna Kyselyova, Nataliia Glushko, Renata Vybyrana, Igor Skrypnyk, Natalya Tretyak, Tetiana Kharchevska, Iryna Dyagil, Tetiana Popovs'ka, Vadim Shimanskiy, Tamila Lysa, Hanna Oliynyk, Kateryna Vilchevskaya, Iryna Kryachok, Yuriy Popovych, Natalia Romanyuk, Natalia Yushchenko, Polina Kaplan, Grygoriy Rekhtman, Halyna Pylypenko, Viktor Kozlov, Johannes Drach, Jean-Luc Harousseau, Hermann Einsele, Hartmut Goldschmidt, Thierry Facon, Mauricette Michalet, Valery G. Savchenko, Javier De la Rubia, Gordon Cook, Ulf-Henrik Mellqvist, Heinz Ludwig, Millennium Pharmaceuticals, Janssen Research and Development, Mohty, Mohamad, Terpos, Evangelo, Mateos, Maria-Victoria, Cavo, Michele, Lejniece, Sandra, Beksac, Meral, Bekadja, Mohamed Amine, Legiec, Wojciech, Dimopoulos, Meletio, Stankovic, Svetlana, Durán, Maria Soledad, De Stefano, Valerio, Corso, Alessandro, Kochkareva, Yulia, Laane, Edward, Berthou, Christian, Salwender, Han, Masliak, Zvenyslava, Pečeliūnas, Valda, Willenbacher, Wolfgang, Silva, João, Louw, Vernon, Nemet, Damir, Borbényi, Zita, Abadi, Uri, Pedersen, Robert Schou, Černelč, Peter, Potamianou, Anna, Couturier, Catherine, Feys, Caroline, Thoret-Bauchet, Florence, Boccadoro, Mario, Mohty, M., Terpos, E., Mateos, M. -V., Cavo, M., Lejniece, S., Beksac, M., Bekadja, M. A., Legiec, W., Dimopoulos, M., Stankovic, S., Duran, M. S., De Stefano, V., Corso, A., Kochkareva, Y., Laane, E., Berthou, C., Salwender, H., Masliak, Z., Peceliunas, V., Willenbacher, W., Silva, J., Louw, V., Nemet, D., Borbenyi, Z., Abadi, U., Pedersen, R. S., Cernelc, P., Potamianou, A., Couturier, C., Feys, C., Thoret-Bauchet, F., Boccadoro, M., Bekadja, M., Hamladji, R. -M., Ali, H. A., Hamdi, S., Touhami, H., Mansour, N. S., Linkesch, W., Abildgaard, N., Hein, M., Eveillard, J. R., Yamani, A. E., Moreau, P., Sanhes, L., Lepeu, G., Laribi, K., Jourdan, E., Fitoussi, O., Allangba, O., Fleury, J., Escoffre, M., Benramdane, R., Cartron, G., Dine, G., Legouffe, E., Harich, H. -D., Illmer, T., Dorfel, S., Hannig, C. V., Koenigsmann, M., Prange-Krex, G., Tamm, I., Zeller, W., Maasberg, M., Schlag, R., Klausmann, M., Uhlig, J., Alkemper, B., Schutz, S., Tessen, H. -W., Mohr, B., Schmidt, P., Heinrich, B., Hebart, H., Seipelt, G., Zoeller, T., Heits, F., Muller-Naendrup, C., Hansen, R., Repp, R., Von Weikersthal, L. F., Schmits, R., Hessling, J., Krammer-Steiner, B., Janzen, V., Schauer, M., Gruner, M. W., Kisro, J., Denzlinger, C., Freier, W., Junghanss, C., Gorner, M., Laichinger, K., Ostermann, H., Durk, H., Hess, G., Reich, G., Matsouka, P., Pouli, A., Anagnostopoulos, A., Masszi, T., Ivanyi, J., Szomor, A., Nagler, A., Magen, H., Avivi, I., Quitt, M., Palumbo, A., Za, T., Vallisa, D., Foa, R., Bosi, A., Vacca, A., Lanza, F., Palazzo, G., Avvisati, G., Ferrara, F., Consoli, U., Cantonetti, M., Angelucci, E., Califano, C., Di Raimondo, F., Guarini, A., Musso, M., Pizzuti, M., Giuliani, N., Ardizzoia, A., Di Renzo, N., Gaidano, G., Gozzetti, A., Pitini, V., Farina, G., Centurioni, R., De Fabritiis, P., Iuliano, F., La Nasa, G., La Verde, G., Pane, F., Recine, U., La Targia, M., Mineo, G., Cangialosi, C., Fagnani, D., Federici, A., Romano, A., Specchia, G., Storti, S., Bongarzoni, V., Bacigalupo, A., Gobbi, M., Latte, G., Mannina, D., Capalbo, S., Jurgutis, M., Woszczyk, D., Holojda, J., Gornik, S., Pluta, A., Morawiec-Szymonik, E., Kyrcz-Krzemien, S., Homenda, W., Grosicki, S., Sulek, K., Lange, A., Kloczko, J., Starzak-Gwozdz, J., Hellmann, A., Komarnicki, M., Kuliczkowski, K., Viveiros, C., Goncalves, C., Esefyeva, N., Kaplanov, K., Volodicheva, E., Laricheva, E., Dergacheva, V., Chukavina, M., Volchenko, N., Nazarova, I., Anchukova, L., Ovanesova, E., Salogub, G., Magomedova, L., Kuznetsova, I., Osyunikhina, S., Serdyuk, O., Karyagina, E., Ivanova, V., Cernelc, S. P., Coetzee, C., Gunther, K., Moodley, D., Duran, S., Gutierrez, A. E., De Oteyza, J. P., Capote, F. J., Casanova, M., Sanchez, J. M., Rios-Herranz, E., Ibanez-Garcia, J., Herranz, M. J., Hernandez, B., Sanchez, S. S., Escalante, F., Carnicero, F., Lleonart, J. B., Gironella, M., Martinez, R., De La Guia, A. L., Palomera, L., Iglesias, R., Ramos, F. S., De La Serna, J., Sanchez, P. G., Vidal, J. B., Morfa, M. D., Beksac, T. -M., Vural, F., Aydin, Y., Unal, A., Goker, H., Bilgir, O., Guvenc, B., Turgut, M., Ozet, G. G., Ali, R., Kyselyova, M., Glushko, N., Vybyrana, R., Skrypnyk, I., Tretyak, N., Kharchevska, T., Dyagil, I., Popovs'Ka, T., Shimanskiy, V., Lysa, T., Oliynyk, H., Vilchevskaya, K., Kryachok, I., Popovych, Y., Romanyuk, N., Yushchenko, N., Kaplan, P., Rekhtman, G., Pylypenko, H., Kozlov, V., Drach, J., Harousseau, J. -L., Einsele, H., Goldschmidt, H., Facon, T., Michalet, M., Savchenko, V. G., De la Rubia, J., Cook, G., Mellqvist, U. -H., Ludwig, H., Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Department of Clinical Therapeutics, Univesrity of Athens, Universidad de Salamanca- CSIC, The Institute of Hematology and Oncology L. and A. Seràgnoli, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Riga Stradins University (RSU), Ankara University, University of Oran Es-Senia [Oran] | Université d'Oran Es-Senia [Oran], Medical University of Lublin, Department of Clinical Therapeutics [Athens, Greece], National and Kapodistrian University of Athens (NKUA), University Clinic of Hematology, Skopje, Complejo Hospitalario de Jaén, Institute of Hematology, Catholic University, Division of Hematology, Foundation IRCCS Policlinico San Matteo, Università degli Studi di Pavia, State Budget Healthcare Insititution of Moscow, North Estonia Medical Centre, Service d'hématologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Asklepios Klinik Altona, Institute of Blood Pathology and Transfusion Medicine, Lviv, Vilnius University Hospital Santariskiu Clinics, Universitätsklinik Innsbruck Innere Medizin V (Innsbruck Austria & Oncotyrol), Instituto de Engenharia de Sistemas e Computadores Investigação e Desenvolvimento em Lisboa (INESC-ID), Instituto Superior Técnico, Universidade Técnica de Lisboa (IST)-Instituto de Engenharia de Sistemas e Computadores (INESC), University Health Network, University of the Free State [South Africa], Clinical Hospital Centre Zagreb, Szegedi Tudományegyetem, Meir Medical Center, Regionshospitalet i Holstebro, Medicinsk Afdeling, University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Janssen-Cilag, Neuss, Janssen-Cilag [Issy-les-Moulineaux], Janssen Research & Development, Divisione di Ematologia dell' Università di Torino, and Azienda Ospedaliera S. Giovanni Battista di Torino

Subjects
Male, Cancer Research, Boronic Acid, [SDV]Life Sciences [q-bio], bortezomib, global, observational study, routine practice, stem cell transplantation, Salvage therapy, Practice Patterns, Dexamethasone, Bortezomib, Routine practice, 0302 clinical medicine, Global, Observational study, Stem cell transplantation, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, 80 and over, Prospective Studies, Practice Patterns, Physicians', Prospective cohort study, Lenalidomide, ComputingMilieux_MISCELLANEOUS, Multiple myeloma, Aged, 80 and over, Hematology, Middle Aged, Boronic Acids, 3. Good health, Thalidomide, Survival Rate, Treatment Outcome, Local, Oncology, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, Adult, Aged, Follow-Up Studies, Humans, Neoplasm Recurrence, Local, Salvage Therapy, medicine.drug, Human, medicine.medical_specialty, NO, Follow-Up Studie, 03 medical and health sciences, Internal medicine, medicine, Survival rate, Physicians', Antineoplastic Combined Chemotherapy Protocol, business.industry, Settore MED/15, medicine.disease, Transplantation, Settore MED/15 - MALATTIE DEL SANGUE, Prospective Studie, Neoplasm Recurrence, business, 030215 immunology
Abstract

© 2018 The Authors., [Background]: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. [Patients and Methods]: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months., [Results]: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide., [Conclusion]: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits., Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc.

Published
2018
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47. Differential cognitive performances between schizophrenic responders and non-responders to antipsychotics: Correlation with course of the illness, psychopathology, attitude to the treatment and antipsychotics doses

Author

Sara Giordano, Felice Iasevoli, Elisabetta F. Buonaguro, Gianmarco Latte, Raffaele Balletta, Andrea de Bartolomeis, DE BARTOLOMEIS, Andrea, Balletta, R, Giordano, S, Buonaguro, Ef, Latte, G, and Iasevoli, Felice

Subjects
Adult, Male, endocrine system, Psychosis, animal structures, medicine.medical_treatment, Psychosi, Verbal memory, Neuropsychological Tests, Antipsychotic, Young Adult, Cognition, Drug Attitude Inventory (DAI), medicine, Humans, Clozapine, Biological Psychiatry, Aged, Psychopathology, Positive and Negative Syndrome Scale, Subjective Well-being under Neuroleptics (SWN), Middle Aged, medicine.disease, Brief Assessment of Cognition in Schizophrenia (BACS), Psychiatry and Mental health, Cross-Sectional Studies, Psychotic Disorders, Schizophrenia, Case-Control Studies, Female, Schizophrenic Psychology, Cognition Disorders, Psychology, hormones, hormone substitutes, and hormone antagonists, Antipsychotic Agents, medicine.drug, Clinical psychology
Abstract

Multiple lines of evidence demonstrate that schizophrenia patients may perform worse than normal controls in several cognitive tasks. However, little is known on putative differences in cognitive functioning between schizophrenia patients responding to antipsychotics and those resistant to the treatment. In this cross-sectional study, 63 subjects (41 schizophrenia and schizoaffective patients and 22 age and sex-matched controls) were enrolled. Patients were divided in resistant (TRS, n=19) and non-resistant to pharmacological treatment (non-TRS, n=22) according to the American Psychiatric Association (APA) criteria for treatment resistance. The Brief Assessment of Cognition in Schizophrenia (BACS) was administered to patients and controls. The following rating scales were administered to schizophrenia patients: the Positive and Negative Syndrome Scale (PANSS), the Drug Attitude Inventory (DAI) and the Subjective Well-being under Neuroleptics (SWN). Statistically significant differences among non-TRS patients, TRS ones, and controls were detected at the BACS. TRS patients performed significantly worse than non-TRS ones on Verbal Memory task, exhibited higher PANSS total and subscales scores and were prescribed higher antipsychotic doses. Poorer performances at the BACS significantly correlated with more severe negative symptoms in TRS but not in non-TRS patients. These results may suggest that TRS patients suffer from a form of the disease with prominent cognitive impairment possibly related to negative symptoms.

Published
2013
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48. Glutamatergic postsynaptic density protein dysfunctions in synaptic plasticity and dendritic spines morphology: relevance to schizophrenia and other behavioral disorders pathophysiology, and implications for novel therapeutic approaches

Author

Carmine Tomasetti, Felice Iasevoli, Andrea de Bartolomeis, Gianmarco Latte, DE BARTOLOMEIS, Andrea, Latte, G, Tomasetti, Carmine, and Iasevoli, Felice

Subjects
Psychosis, Dendritic spine, Dendritic Spines, Neuroscience (miscellaneous), HOMER1, Glutamic Acid, Psychosi, Nerve Tissue Proteins, Antipsychotic, Shank, Cellular and Molecular Neuroscience, Drug Delivery Systems, mental disorders, medicine, Animals, Humans, PSD-95, Neuronal Plasticity, Mental Disorders, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Glutamatergic postsynaptic density, medicine.disease, Synapse, Homer, nervous system, Neurology, Schizophrenia, Child Development Disorders, Pervasive, Synaptic plasticity, Synapses, Autism, Psychology, Neuroscience, Postsynaptic density, Disks Large Homolog 4 Protein, Antipsychotic Agents
Abstract

Emerging researches point to a relevant role of postsynaptic density (PSD) proteins, such as PSD-95, Homer, Shank, and DISC-1, in the pathophysiology of schizophrenia and autism spectrum disorders. The PSD is a thickness, detectable at electronic microscopy, localized at the postsynaptic membrane of glutamatergic synapses, and made by scaffolding proteins, receptors, and effector proteins; it is considered a structural and functional crossroad where multiple neurotransmitter systems converge, including the dopaminergic, serotonergic, and glutamatergic ones, which are all implicated in the pathophysiology of psychosis. Decreased PSD-95 protein levels have been reported in postmortem brains of schizophrenia patients. Variants of Homer1, a key PSD protein for glutamate signaling, have been associated with schizophrenia symptoms severity and therapeutic response. Mutations in Shank gene have been recognized in autism spectrum disorder patients, as well as reported to be associated to behaviors reminiscent of schizophrenia symptoms when expressed in genetically engineered mice. Here, we provide a critical appraisal of PSD proteins role in the pathophysiology of schizophrenia and autism spectrum disorders. Then, we discuss how antipsychotics may affect PSD proteins in brain regions relevant to psychosis pathophysiology, possibly by controlling synaptic plasticity and dendritic spine rearrangements through the modulation of glutamate-related targets. We finally provide a framework that may explain how PSD proteins might be useful candidates to develop new therapeutic approaches for schizophrenia and related disorders in which there is a need for new biological treatments, especially against some symptom domains, such as negative symptoms, that are poorly affected by current antipsychotics.

Published
2013

49. The expression of genes involved in glucose metabolism is affected by N-methyl-D-aspartate receptor antagonism: a putative link between metabolism and an animal model of psychosis

Author

Andrea de Bartolomeis, Chiara Sarappa, Felice Iasevoli, Gianmarco Latte, Luigi Aloj, Livia Avvisati, Iasevoli, Felice, Latte, G, Avvisati, L, Sarappa, C, Aloj, L, and DE BARTOLOMEIS, Andrea

Subjects
Male, Psychosis, striatum, glutamate, Convulsants, Carbohydrate metabolism, Pharmacology, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Dopamine, Hexokinase, medicine, Image Processing, Computer-Assisted, Animals, RNA, Messenger, In Situ Hybridization, biology, Glucose Transporter Type 3, Glutamate receptor, Glucose transporter, Brain, medicine.disease, Rats, schizophrenia, Disease Models, Animal, Glucose, chemistry, Psychotic Disorders, Schizophrenia, biology.protein, Autoradiography, Ketamine, dopamine, Psychology, Transcriptome, medicine.drug, GLUT3
Abstract

Psychosis has been associated with glucose metabolism impairment. Here, we explored the gene expression of hexokinase 1 (Hk1) and glucose transporter 3 (GLUT3) after the administration of a subanesthetic or a subconvulsant dose of ketamine in rats, considered to provide an animal model of psychosis. Indeed, Hk1 and GLUT3 are crucially involved in the glucose utilization in brain tissues and have also been implicated in the pathophysiology of psychosis. Quantitative brain imaging of transcripts was used to evaluate Hk1 and GLUT3 mRNA in rat brain regions related to ketamineinduced behavioral abnormalities. Hk1 transcript was significantly increased by 50 mg/kg ketamine in cortical and subcortical areas, whereas 12 mg/kg ketamine affected Hk1 expression in the auditory cortex only. GLUT3 expression was increased by 12 mg/kg ketamine in the frontal cortex and decreased by 50 mg/kg ketamine in subcortical areas. The results show that Hk1 and GLUT3 are extensively and differentially affected by ketamine dose, supporting the view that glucose metabolism and psychosis may be causally related and suggesting that these molecules may play a role in the pathophysiology of ketamine-induced behavioral abnormalities. V C 2012 Wiley Periodicals, Inc.

Published
2011

50. Temozolomide as salvage treatment in primary brain lymphomas

Author

Michele Reni, Gaetano Corazzelli, Roberto Bordonaro, A Abbadessa, Marina Faedi, Caterina Stelitano, Andrea Pace, Giancarlo Latte, P Manno, A. J. M. Ferreri, Enrico Franceschi, Michele Spina, James Perry, Elena Mazza, Warren P. Mason, M Candela, Fiorella Ilariucci, Francesco Zaja, Reni, M, Zaja, Francesco, Mason, W, Perry, J, Mazza, E, Spina, M, Bordonaro, R, Ilariucci, F, Faedi, M, Corazzelli, G, Manno, P, Franceschi, E, Pace, A, Candela, M, Abbadessa, A, Stelitano, C, Latte, G, Ferreri, A. J., Zaja, F, and Ferreri, Ajm

Subjects
Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Lymphoma, Dacarbazine, medicine.medical_treatment, Salvage therapy, primary brain lymphoma, Internal medicine, Clinical Studies, Temozolomide, Medicine, Humans, phase II trial, Antineoplastic Agents, Alkylating, Aged, Aged, 80 and over, Salvage Therapy, Chemotherapy, business.industry, Brain Neoplasms, Middle Aged, medicine.disease, Surgery, Clinical trial, Radiation therapy, Methotrexate, Female, Neoplasm Recurrence, Local, business, medicine.drug
Abstract

Methotrexate (MTX)-based chemotherapy extends survival in patients with primary brain lymphomas, but it is not clear whether multiagent chemotherapy is superior to MTX alone. Treatment options for patients with recurrent primary brain lymphoma are limited; there is no standard second-line chemotherapy. New chemotherapeutic agents with clear activity in brain lymphoma are needed for treatment of recurrent disease. We report the results of a phase II trial assessing activity of the alkylating agent temozolomide in immunocompetent patients with recurrent primary brain lymphomas, previously treated with high-dose MTX-containing chemotherapy and/or radiotherapy. A median of two courses (range 1-12) of temozolomide 150 mg m(-2) day(-1), for 5 days every 4 weeks was administered to 36 patients yielding nine complete and two partial responses (response rate: 31%; 95% confidence interval 16-46%). One-year survival was 31% ( 95% confidence interval 16-46%). Toxicity was negligible. We conclude that temozolomide is active in recurrent primary brain lymphomas and should further be evaluated in this disease, perhaps in combination with MTX as initial treatment.

Published
2007

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