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1,445 results on '"Torelli, G."'

56. An integrated CMOS interface for lambda sensor

Author

Civardi, L., Gatti, U., Maloberti, F., and Torelli, G.

Subjects
Complementary metal oxide semiconductors -- Research, Automobiles -- Pollution control devices, Sensors -- Research, Business, Electronics, Electronics and electrical industries, Transportation industry
Abstract

Automotive pollution can be reduced by suitably controlling the mixture that is fed to the cylinders. This can be performed by means of a feedback loop including a lambda sond and a processing unit which controls the electronic fuel injectors. This paper describes a CMOS interface which adapts the output signal of a lambda sensor to allow its feeding into the processing unit. It provides a differential to a single-ended conversion with a good common mode rejection, a level shifting around a given reference voltage, and an accurate voltage gain. Both design considerations and the measurements performed on an integrated test structure are presented. The measured variation of the large-signal voltage gain for an input signal of 0 to 1 V is within + or - 5% when the input common mode voltage ranges from -1 V to 1 V with respect to the negative supply voltage. An output voltage with a precision within + or - mV is obtained in the presence of an input voltage corresponding to the stochiometric composition of the mixture.

Published
1994

57. A digital front-end and readout microsystem for calorimetry at LHC: the FERMI project

Author

Dell'Acqua, A., Hansen, M., Loftstedt, B., Vanuxem, J.P., Svensson, C., Yuan, J., Hentzell, H., Alippi, C., Breveglieri, L., Dadda, L., Piuri, V., Salice, F., Sami, M., Stefanelli, R., Cattaneo, P., Fumagalli, G., Goggi, V.G., Brigati, S., Gatti, U., Maloberti, F., Torelli, G., Carlson, P., Fuglesang, C., Kerek, A., and Appelquist, G.

Subjects
Calorimeters -- Research, Proton accelerators -- Research, Hadrons -- Measurement, Business, Electronics, Electronics and electrical industries
Abstract

We present a digital solution to the front-end electronics for calorimetric detectors at future supercolliders based on high speed A/D converters, a fully programmable pipeline/digital filter chain and local intelligence. Questions of error correction, fault-tolerance and system redundancy are also considered. A system integration of a multichannel device in a multichip, Silicon-on-Silicon Microsystem hybrid will be used. This solution allows a new level of integration of complex analog and digital functions, with an excellent flexibility in mixing technologies for the different functional blocks. This type of VLSI multichip integration allows a high degree of programmability at both the function and the system level, and offers the possibility of customizing the microsystem with detector-specific functions.

Published
1993

59. The Virgo Project

Author

Vinet, Jean-Yves, primary, Bondu, F., additional, Brillet, A., additional, Cleva, F., additional, Heitmann, H., additional, Latrach, L., additional, Man, N., additional, Pham Tu, M., additional, Barsuglia, M., additional, Brisson, V., additional, Cavalier, F., additional, Davier, M., additional, Hello, P., additional, Heusse, P., additional, Lediberder, F., additional, Marin, P., additional, Caron, B., additional, Dominjon, A., additional, Drezen, C., additional, Flaminio, R., additional, Grave, X., additional, Marion, F., additional, Massonet, L., additional, Mehmel, C., additional, Morand, R., additional, Mours, B., additional, Sannibale, V., additional, Yvert, M., additional, Dognin, L., additional, Ganau, P., additional, Lagrange, B., additional, Mackowski, J.-M., additional, Michel, C., additional, Morgue, M., additional, Napolitano, M., additional, Pinard, L., additional, Boccara, C., additional, Gleyzes, P., additional, Loriette, V., additional, Roger, J.-P., additional, Bernardini, M., additional, Braccini, S., additional, Bradaschia, C., additional, Del Fabbro, R., additional, De Salvo, R., additional, Di Virgilio, A., additional, Ferrante, I., additional, Fidecaro, F., additional, Gennai, A., additional, Giassi, A., additional, Giazotto, A., additional, Holloway, L., additional, La Penna, P., additional, Losurdo, G., additional, Palla, F., additional, Pan, H., additional, Pasqualetti, A., additional, Passuello, D., additional, Poggiani, R., additional, Torelli, G., additional, Zhang, Z., additional, Babusci, D., additional, Bellucci, S., additional, Candusso, G., additional, Giordano, G., additional, Matone, G., additional, Majorana, E., additional, Puppo, P., additional, Rapagnani, P., additional, Ricci, F., additional, Cagnoli, G., additional, Gammaitoni, L., additional, Kovalik, J., additional, Marchesoni, F., additional, Punturo, M., additional, Barone, F., additional, Calloni, E., additional, Di Fiore, L., additional, Grado, A., additional, Milano, L., additional, Russo, G., additional, and Solimeno, S., additional

Published
1997
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61. 2-Mb Embedded Phase Change Memory With 16-ns Read Access Time and 5-Mb/s Write Throughput in 90-nm BCD Technology for Automotive Applications

Author

Carissimi, M., primary, Mukherjee, R., additional, Tyagi, V., additional, Disegni, F., additional, Manfre, D., additional, Torti, C., additional, Gallinari, D., additional, Rossi, S., additional, Gambero, A., additional, Brambilla, D., additional, Zuliani, P., additional, Zurla, R., additional, Cabrini, A., additional, Torelli, G., additional, Pasotti, M., additional, Auricchio, C., additional, Calvetti, E., additional, Capecchi, L., additional, Croce, L., additional, Zanchi, S., additional, Rana, V., additional, and Mishra, P., additional

Published
2019
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67. Antiglioma effects of N6-isopentenyladenosine, an endogenous isoprenoid end product, through the downregulation of epidermal growth factor receptor

Author

Ciaglia E., Abate M., Laezza C., Pisanti S., Vitale M., Seneca V., Torelli G., Franceschelli S., Catapano G., Gazzerro P., and Bifulco M.

Subjects
AMPK, isoprenoids, EGFR, skin and connective tissue diseases, signaling, GBM, respiratory tract diseases
Abstract

Malignant gliomas are highly dependent on the isoprenoid pathway for the synthesis of lipid moieties critical for cell proliferation. The isoprenoid derivative N6-isopentenyladenosine (iPA) displays pleiotropic biological effects, including a direct anti-tumor activity in several tumor models. The antiglioma effects of iPA was then explored in U87MG cells both in vitro and grafted in mice and the related molecular mechanism confirmed in primary derived patients' glioma cells. iPA powerfully inhibited tumor cell growth and induced caspase-dependent apoptosis through a mechanism involving a marked accumulation of the pro-apoptotic BIM protein and inhibition of EGFR. Indeed, activating AMPK following conversion into its iPAMP active form, iPA stimulated EGFR phosphorylation and ubiquitination along a proteasome-mediated pathway which was responsible for receptor degradation and its downstream signaling pathways inhibition, including the STAT3, ERK and AKT cascade. The inhibition of AMPK by compound C prevented iPA-mediated phosphorylation of EGFR, known to precede receptor loss. As expected the block of EGFR degradation, by exposure to the proteasome inhibitor MG132, significantly reduced iPA-induced cell death. Given the importance of receptor degradation in iPA-mediated cytotoxicity, we also documented that the EGFR expression levels in a panel of primary glioma cells confers them a high sensitivity to iPA treatment. In conclusion our study provides the first evidence of iPA antiglioma effect. Indeed, as glioma is driven by aberrant signaling of growth factor receptors, particularly the EGFR, iPA, alone or in association with EGFR targeted therapies, might be a promising therapeutic tool to achieve a potent anti-tumoral effect.

Published
2017
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76. The INFN Eloisatron Project: European Long Intersecting Storage Accelerator

Author

Aglietta, C., Alberini, K., Badino, G., Bari, G., Basile, M., Bassetti, M., Berbiers, J., Bertin, A., Boschi, E., Braginski, V., Bruzzese, R., Cabibbo, N., Romeo, G. Cara, Casaccia, R., Castagnoli, C., Castellina, A., Castelvetri, A., Cifarelli, L., Cindolo, F., Civita, M., Contin, A., D’Ali, G., Dardo, M., Del Papa, C., de Sabbata, V., Ferrario, L., Fulgione, W., Galassini, S., Galeotti, P., Gasperini, M., Giusti, P., Goldoni, R., Iacobucci, G., Laakso, I., Leo, A. R., Leo, M., Luches, G., Maccarrone, G., Marino, A., Massam, T., Melnikov, V. N., Meunier, R., Motta, F., Nania, R., Nassissi, V., Navarra, G., Palmonari, F., Papini, G., Passotti, G., Pelfer, P., Pocci, G., Prisco, G., Puglisi, M., Ricci, M., Rinaldi, G., Rizzuto, C., Rohrbach, F., Rotelli, P., Saavedra, O., Sacchetti, N., Sartorelli, G., Soliani, G., Spadoni, M., Steuer, M., Susinno, G., Tazzari, S., Thorne, K., Torelli, G., Trinchero, G. C., Vallania, P., Venturi, G., Vernetto, S., Villa, F., Vitale, A., Votano, L., Willutzky, M., Zichichi, A., Zichichi, Antonino, editor, and Villa, Francesco, editor

Published
1988
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81. A 32KB 18ns random access time embedded PCM with enhanced program throughput for automotive and smart power applications

Author

Pasotti, M., primary, Carissimi, M., additional, Auricchio, C., additional, Brambilla, D., additional, Calvetti, E., additional, Capecchi, L., additional, Croce, L., additional, Gallinari, D., additional, Mazzaglia, C., additional, Rana, V., additional, Zurla, R., additional, Cabrini, A., additional, and Torelli, G., additional

Published
2017
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83. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma

Author

Cavo, M, Pantani, L, Petrucci, M, Patriarca, F, Zamagni, E, Donnarumma, D, Crippa, C, Boccadoro, M, Perrone, G, Falcone, A, Nozzoli, C, Zambello, R, Masini, L, Furlan, A, Brioli, A, Derudas, D, Ballanti, S, Dessanti, M, De Stefano, V, Carella, A, Marcatti, M, Nozza, A, Ferrara, F, Callea, V, Califano, C, Pezzi, A, Baraldi, A, Grasso, M, Musto, P, Palumbo, A, Tosi, P, Motta, M, Rizzi, S, Fanin, R, Buttignol, S, Foà, R, Levi, A, Calabrese, E, Rambaldi, A, Galli, M, Rossi, G, Ferrari, S, Bringhen, S, Leoni, P, Offidani, M, Polloni, C, Corradini, P, Montefusco, V, Torelli, G, Narni, F, Fioritoni, G, Spadano, A, Cortelazzo, S, Pescosta, N, Billio, A, Lambertenghi Deliliers, G, Baldini, L, Onida, F, Annaloro, C, La Nasa, G, Ledda, A, Zaccaria, A, Cellini, C, De Fabritiis, P, Caravita, T, Siniscalchi, A, Cascavilla, N, Bosi, A, Semenzato, G, Gugliotta, L, Merli, F, Gherlinzoni, F, Angelucci, E, Martelli, M, Petti, M, Pisani, F, Leone, G, Rossi, E, Za, T, Fianchi, L, Catania, G, Spriano, M, Ciceri, F, Peccatori, J, Girlanda, S, Santoro, A, Castagna, L, Palmieri, S, Nobile, F, D'Arco, A, Levis, A, Primon, V, Tamiazzo, S, Guardigni, L, Pasini, S, Gallamini, A, Pietrantuono, G, Martorelli, M, Fattori, P, Pasquini, E, Galieni, P, Ruggieri, M, Morandi, S, Tajana, M, Amadori, D, Ronconi, S, Cangini, D, Ceccolini, M, Gobbi, M, Ballerini, F, Pane, F, Catalano, L, Cangialosi, C, Vallisa, D, Lazzaro, A, Paladini, G, De Sabbata, G, Mozzana, R, Ciambelli, F, Pinotti, G, Rodeghiero, F, Elice, F, Cantore, N, Volpe, S, Pavone, V, Mele, A, Pogliani, E, Rossini, F, Liberati, A, Majolino, I, De Rosa, L, Amadori, S, Rizzo, M, Lauria, F, Gozzetti, A, Aglietta, M, Capaldi, A, Quarta, G, Mele, G, Storti, S, Fraticelli, V, Morabito, F, Gentile, C, Capalbo, S, Gianni, A, Magni, M, Mettivier, V, Nunziata, G, Rizzoli, V, Giuliani, N, Crugnola, M, Bernasconi, C, Fregoni, V, Visani, G, Olivieri, A, Pizzuti, M, La Verde, G, Moscetti, A, Avvisati, G, Tirindelli, M, Longinotti, M, Podda, L, Gallo, E, Pregno, P, Dammacco, F, Perosa, F, Russo, D, Roccaro, A, Bacigalupo, A, Dominietto, A, Musolino, C, Quartarone, E, Tosi P, Motta MR, Rizzi S, Fanin R, Buttignol S, Foà R, Levi A, Calabrese E, Rambaldi A, Galli M, Rossi G, Ferrari S, Bringhen S, Leoni P, Offidani M, Polloni C, Corradini P, Montefusco V, Torelli G, Narni F, Fioritoni G, Spadano A, Cortelazzo S, Pescosta N, Billio A, Lambertenghi Deliliers G, Baldini L, Onida F, Annaloro C, La Nasa G, Ledda A, Zaccaria A, Cellini C, De Fabritiis P, Caravita T, Siniscalchi A, Cascavilla N, Bosi A, Semenzato G, Gugliotta L, Merli F, Gherlinzoni F, Angelucci E, Martelli M, Petti MC, Pisani F, Leone G, Rossi E, Za T, Fianchi L, Catania G, Spriano M, Ciceri F, Peccatori J, Girlanda S, Santoro A, Castagna L, Palmieri S, Nobile F, D'Arco AM, Levis A, Primon V, Tamiazzo S, Guardigni L, Pasini S, Gallamini A, Pietrantuono G, Martorelli MC, Fattori P, Pasquini E, Galieni P, Ruggieri M, Morandi S, Tajana M, Amadori D, Ronconi S, Cangini D, Ceccolini M, Gobbi M, Ballerini F, Pane F, Catalano L, Cangialosi C, Vallisa D, Lazzaro A, Paladini G, De Sabbata G, Mozzana R, Ciambelli F, Pinotti G, Rodeghiero F, Elice F, Cantore N, Volpe S, Pavone V, Mele A, POGLIANI, ENRICO MARIA, Rossini F, Liberati A, Majolino I, De Rosa L, Amadori S, Rizzo M, Lauria F, Gozzetti A, Aglietta M, Capaldi A, Quarta G, Mele G, Storti S, Fraticelli V, Morabito F, Gentile C, Capalbo S, Gianni A, Magni M, Mettivier V, Nunziata G, Rizzoli V, Giuliani N, Crugnola M, Bernasconi C, Fregoni V, Visani G, Olivieri A, Pizzuti M, La Verde G, Moscetti A, Avvisati G, Tirindelli M, Longinotti M, Podda L, Gallo E, Pregno P, Dammacco F, Perosa F, Russo D, Roccaro A, Bacigalupo A, Dominietto A, Musolino C, Quartarone E., Cavo, M, Pantani, L, Petrucci, M, Patriarca, F, Zamagni, E, Donnarumma, D, Crippa, C, Boccadoro, M, Perrone, G, Falcone, A, Nozzoli, C, Zambello, R, Masini, L, Furlan, A, Brioli, A, Derudas, D, Ballanti, S, Dessanti, M, De Stefano, V, Carella, A, Marcatti, M, Nozza, A, Ferrara, F, Callea, V, Califano, C, Pezzi, A, Baraldi, A, Grasso, M, Musto, P, Palumbo, A, Tosi, P, Motta, M, Rizzi, S, Fanin, R, Buttignol, S, Foà, R, Levi, A, Calabrese, E, Rambaldi, A, Galli, M, Rossi, G, Ferrari, S, Bringhen, S, Leoni, P, Offidani, M, Polloni, C, Corradini, P, Montefusco, V, Torelli, G, Narni, F, Fioritoni, G, Spadano, A, Cortelazzo, S, Pescosta, N, Billio, A, Lambertenghi Deliliers, G, Baldini, L, Onida, F, Annaloro, C, La Nasa, G, Ledda, A, Zaccaria, A, Cellini, C, De Fabritiis, P, Caravita, T, Siniscalchi, A, Cascavilla, N, Bosi, A, Semenzato, G, Gugliotta, L, Merli, F, Gherlinzoni, F, Angelucci, E, Martelli, M, Petti, M, Pisani, F, Leone, G, Rossi, E, Za, T, Fianchi, L, Catania, G, Spriano, M, Ciceri, F, Peccatori, J, Girlanda, S, Santoro, A, Castagna, L, Palmieri, S, Nobile, F, D'Arco, A, Levis, A, Primon, V, Tamiazzo, S, Guardigni, L, Pasini, S, Gallamini, A, Pietrantuono, G, Martorelli, M, Fattori, P, Pasquini, E, Galieni, P, Ruggieri, M, Morandi, S, Tajana, M, Amadori, D, Ronconi, S, Cangini, D, Ceccolini, M, Gobbi, M, Ballerini, F, Pane, F, Catalano, L, Cangialosi, C, Vallisa, D, Lazzaro, A, Paladini, G, De Sabbata, G, Mozzana, R, Ciambelli, F, Pinotti, G, Rodeghiero, F, Elice, F, Cantore, N, Volpe, S, Pavone, V, Mele, A, Pogliani, E, Rossini, F, Liberati, A, Majolino, I, De Rosa, L, Amadori, S, Rizzo, M, Lauria, F, Gozzetti, A, Aglietta, M, Capaldi, A, Quarta, G, Mele, G, Storti, S, Fraticelli, V, Morabito, F, Gentile, C, Capalbo, S, Gianni, A, Magni, M, Mettivier, V, Nunziata, G, Rizzoli, V, Giuliani, N, Crugnola, M, Bernasconi, C, Fregoni, V, Visani, G, Olivieri, A, Pizzuti, M, La Verde, G, Moscetti, A, Avvisati, G, Tirindelli, M, Longinotti, M, Podda, L, Gallo, E, Pregno, P, Dammacco, F, Perosa, F, Russo, D, Roccaro, A, Bacigalupo, A, Dominietto, A, Musolino, C, Quartarone, E, Tosi P, Motta MR, Rizzi S, Fanin R, Buttignol S, Foà R, Levi A, Calabrese E, Rambaldi A, Galli M, Rossi G, Ferrari S, Bringhen S, Leoni P, Offidani M, Polloni C, Corradini P, Montefusco V, Torelli G, Narni F, Fioritoni G, Spadano A, Cortelazzo S, Pescosta N, Billio A, Lambertenghi Deliliers G, Baldini L, Onida F, Annaloro C, La Nasa G, Ledda A, Zaccaria A, Cellini C, De Fabritiis P, Caravita T, Siniscalchi A, Cascavilla N, Bosi A, Semenzato G, Gugliotta L, Merli F, Gherlinzoni F, Angelucci E, Martelli M, Petti MC, Pisani F, Leone G, Rossi E, Za T, Fianchi L, Catania G, Spriano M, Ciceri F, Peccatori J, Girlanda S, Santoro A, Castagna L, Palmieri S, Nobile F, D'Arco AM, Levis A, Primon V, Tamiazzo S, Guardigni L, Pasini S, Gallamini A, Pietrantuono G, Martorelli MC, Fattori P, Pasquini E, Galieni P, Ruggieri M, Morandi S, Tajana M, Amadori D, Ronconi S, Cangini D, Ceccolini M, Gobbi M, Ballerini F, Pane F, Catalano L, Cangialosi C, Vallisa D, Lazzaro A, Paladini G, De Sabbata G, Mozzana R, Ciambelli F, Pinotti G, Rodeghiero F, Elice F, Cantore N, Volpe S, Pavone V, Mele A, POGLIANI, ENRICO MARIA, Rossini F, Liberati A, Majolino I, De Rosa L, Amadori S, Rizzo M, Lauria F, Gozzetti A, Aglietta M, Capaldi A, Quarta G, Mele G, Storti S, Fraticelli V, Morabito F, Gentile C, Capalbo S, Gianni A, Magni M, Mettivier V, Nunziata G, Rizzoli V, Giuliani N, Crugnola M, Bernasconi C, Fregoni V, Visani G, Olivieri A, Pizzuti M, La Verde G, Moscetti A, Avvisati G, Tirindelli M, Longinotti M, Podda L, Gallo E, Pregno P, Dammacco F, Perosa F, Russo D, Roccaro A, Bacigalupo A, Dominietto A, Musolino C, and Quartarone E.

Abstract

In a randomized, phase 3 study, superior complete/near-complete response (CR/nCR) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) versus thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autologous stem cell transplantation for newly diagnosed myeloma patients (intention-to-treat analysis; VTD, n = 236; TD, n = 238). This per-protocol analysis (VTD, n = 160; TD, n = 161) specifically assessed the efficacy and safety of consolidation with VTD or TD. Before starting consolidation, CR/nCR rates were not significantly different in the VTD (63.1%) and TD arms (54.7%). After consolidation, CR (60.6% vs 46.6%) and CR/nCR (73.1% vs 60.9%) rates were significantly higher for VTD-treated versus TD-treated patients. VTD consolidation significantly increased CR and CR/nCR rates, but TD did not (McNemar test). With a median follow-up of 30.4 months from start of consolidation, 3-year progression-free survival was significantly longer for the VTD group (60% vs 48% for TD). Grade 2 or 3 peripheral neuropathy (8.1% vs 2.4%) was more frequent with VTD (grade 3, 0.6%) versus TD consolidation. The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation. VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients randomly assigned to the VTD arm of the study. The study is registered at www.clinicaltrials.gov as #NCT01134484.

Published
2012

85. Myeloablative, reduced toxicity versus standard conditioning in AML: a randomized clinical trial from Gruppo Italiano Trapianto di Midollo Osseo (GITMO)

Author

Grassi, A., Mico, C., Oldani, E., Boschini, C., Busca, A., Benedetto, B., Cavattoni, I., Santarone, S., Raimondi, R., Montanari, M., Milone, G., Patrizia Chiusolo, Specchia, G., Guidi, S., Patriarca, F., Bacigalupo, A., Risitano, A. M., Saporiti, G., Pini, M., Pogliani, E. M., Arcese, W., Marotta, G., Carella, A. M., Nagler, A., Corradini, P., Russo, D., Alessandrino, E. P., Torelli, G. F., Mordini, N., Scime, R., Bosi, A., Masciulli, A., Marfisi, R. M., and Rambaldi, A.

Published
2015

87. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy following autologous hematopoietic stem-cell transplantation in patients with newly diagnosed multiple myeloma

Author

Cavo, Michele, Pantani, Lucia, Petrucci, Maria Teresa, Patriarca, Francesca, Zamagni, Elena, Donnarumma, Daniela, Crippa, Claudia, Boccadoro, Mario, Perrone, Giulia, Falcone, Antonietta, Nozzoli, Chiara, Zambello, Renato, Masini, Luciano, Furlan, Anna, Brioli, Annamaria, Derudas, Daniele, Ballanti, Stelvio, Dessanti, Maria Laura, De Stefano, Valerio, Carella, Angelo Michele, Marcatti, Magda, Nozza, Andrea, Ferrara, Felicetto, Callea, Vincenzo, Califano, Catello, Pezzi, Annalisa, Baraldi, Anna, Grasso, Mariella, Musto, Pellegrino, Palumbo, Antonio COLLABORATORI: Tosi, P, Motta, Mr, Rizzi, S, Fanin, R, Buttignol, S, Foà, R, Levi, A, Calabrese, E, Rambaldi, A, Galli, M, Rossi, G, Ferrari, S, Bringhen, S, Leoni, P, Offidani, M, Polloni, C, Corradini, P, Montefusco, V, Torelli, G, Narni, Franco, Fioritoni, G, Spadano, A, Cortelazzo, S, Pescosta, N, Billio, A, Lambertenghi Deliliers, G, Baldini, L, Onida, F, Annaloro, C, La Nasa, G, Ledda, A, Zaccaria, A, Cellini, C, De Fabritiis, P, Caravita, T, Siniscalchi, A, Cascavilla, N, Bosi, A, Semenzato, G, Gugliotta, L, Merli, F, Gherlinzoni, F, Angelucci, E, Martelli, M, Petti, Mc, Pisani, F, Leone, G, Rossi, E, Za, T, Fianchi, L, Catania, G, Spriano, M, Ciceri, F, Peccatori, J, Girlanda, S, Santoro, A, Castagna, L, Palmieri, S, Nobile, F, D'Arco, Am, Levis, A, Primon, V, Tamiazzo, S, Guardigni, L, Pasini, S, Gallamini, A, Pietrantuono, G, Martorelli, Mc, Fattori, P, Pasquini, E, Galieni, P, Ruggieri, M, Morandi, S, Tajana, M, Amadori, D, Ronconi, S, Cangini, D, Ceccolini, M, Gobbi, M, Ballerini, F, Pane, F, Catalano, L, Cangialosi, C, Vallisa, D, Lazzaro, A, Paladini, G, De Sabbata, G, Mozzana, R, Ciambelli, F, Pinotti, G, Rodeghiero, F, Elice, F, Cantore, N, Volpe, S, Pavone, V, Mele, A, Pogliani, E, Rossini, F, Liberati, A, Majolino, I, De Rosa, L, Amadori, S, Rizzo, M, Lauria, F, Gozzetti, A, Aglietta, M, Capaldi, A, Quarta, G, Mele, G, Storti, S, Fraticelli, V, Morabito, F, Gentile, C, Capalbo, S, Gianni, A, Magni, M, Mettivier, V, Nunziata, G, Rizzoli, V, Giuliani, N, Crugnola, M, Bernasconi, C, Fregoni, V, Visani, G, Olivieri, A, Pizzuti, M, La Verde, G, Moscetti, A, Avvisati, G, Tirindelli, M, Longinotti, M, Podda, L, Gallo, E, Pregno, P, Dammacco, F, Perosa, F, Russo, D, Roccaro, A, Bacigalupo, A, Dominietto, A, Musolino, C, Quartarone, E., Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A., Cavo, Michele, Pantani, Lucia, Petrucci, Maria Teresa, Patriarca, Francesca, Zamagni, Elena, Donnarumma, Daniela, Crippa, Claudia, Boccadoro, Mario, Perrone, Giulia, Falcone, Antonietta, Nozzoli, Chiara, Zambello, Renato, Masini, Luciano, Furlan, Anna, Brioli, Annamaria, Derudas, Daniele, Ballanti, Stelvio, Dessanti, Maria Laura, De Stefano, Valerio, Carella, Angelo Michele, Marcatti, Magda, Nozza, Andrea, Ferrara, Felicetto, Callea, Vincenzo, Califano, Catello, Pezzi, Annalisa, Baraldi, Anna, Grasso, Mariella, Musto, Pellegrino, Palumbo, Antonio, Cavo, M, Pantani, L, Petrucci, M, Patriarca, F, Zamagni, E, Donnarumma, D, Crippa, C, Boccadoro, M, Perrone, G, Falcone, A, Nozzoli, C, Zambello, R, Masini, L, Furlan, A, Brioli, A, Derudas, D, Ballanti, S, Dessanti, M, De Stefano, V, Carella, A, Marcatti, M, Nozza, A, Ferrara, F, Callea, V, Califano, C, Pezzi, A, Baraldi, A, Grasso, M, Musto, P, Palumbo, A, Tosi, P, Motta, M, Rizzi, S, Fanin, R, Buttignol, S, Foà, R, Levi, A, Calabrese, E, Rambaldi, A, Galli, M, Rossi, G, Ferrari, S, Bringhen, S, Leoni, P, Offidani, M, Polloni, C, Corradini, P, Montefusco, V, Torelli, G, Narni, F, Fioritoni, G, Spadano, A, Cortelazzo, S, Pescosta, N, Billio, A, Lambertenghi Deliliers, G, Baldini, L, Onida, F, Annaloro, C, La Nasa, G, Ledda, A, Zaccaria, A, Cellini, C, De Fabritiis, P, Caravita, T, Siniscalchi, A, Cascavilla, N, Bosi, A, Semenzato, G, Gugliotta, L, Merli, F, Gherlinzoni, F, Angelucci, E, Martelli, M, Petti, M, Pisani, F, Leone, G, Rossi, E, Za, T, Fianchi, L, Catania, G, Spriano, M, Ciceri, F, Peccatori, J, Girlanda, S, Santoro, A, Castagna, L, Palmieri, S, Nobile, F, D'Arco, A, Levis, A, Primon, V, Tamiazzo, S, Guardigni, L, Pasini, S, Gallamini, A, Pietrantuono, G, Martorelli, M, Fattori, P, Pasquini, E, Galieni, P, Ruggieri, M, Morandi, S, Tajana, M, Amadori, D, Ronconi, S, Cangini, D, Ceccolini, M, Gobbi, M, Ballerini, F, Pane, F, Catalano, L, Cangialosi, C, Vallisa, D, Lazzaro, A, Paladini, G, De Sabbata, G, Mozzana, R, Ciambelli, F, Pinotti, G, Rodeghiero, F, Elice, F, Cantore, N, Volpe, S, Pavone, V, Mele, A, Pogliani, E, Rossini, F, Liberati, A, Majolino, I, De Rosa, L, Amadori, S, Rizzo, M, Lauria, F, Gozzetti, A, Aglietta, M, Capaldi, A, Quarta, G, Mele, G, Storti, S, Fraticelli, V, Morabito, F, Gentile, C, Capalbo, S, Gianni, A, Magni, M, Mettivier, V, Nunziata, G, Rizzoli, V, Giuliani, N, Crugnola, M, Bernasconi, C, Fregoni, V, Visani, G, Olivieri, A, Pizzuti, M, La Verde, G, Moscetti, A, Avvisati, G, Tirindelli, M, Longinotti, M, Podda, L, Gallo, E, Pregno, P, Dammacco, F, Perosa, F, Russo, D, Roccaro, A, Bacigalupo, A, Dominietto, A, Musolino, C, and Quartarone, E

Subjects
Male, Boronic Acid, medicine.medical_treatment, PLUS DEXAMETHASONE, Phases of clinical research, Kaplan-Meier Estimate, Hematopoietic stem cell transplantation, Biochemistry, Antineoplastic Agent, Bortezomib-thalidomide-dexamethasone, Bortezomib, Immunosuppressive Agent, Autologous stem-cell transplantation, MULTIPLE MYELOMA, Antineoplastic Combined Chemotherapy Protocols, thalidomide-dexamethasone, Multiple myeloma, RANDOMIZED PHASE-3, LENALIDOMIDE, STEM CELL TRANSPLANTATION, Hematopoietic Stem Cell Transplantation, PHASE-III TRIAL, Hematology, Middle Aged, CHEMOTHERAPY, Prognosis, Boronic Acids, Combined Modality Therapy, Thalidomide, Transplantation, Autologou, Pyrazines, HIGH-DOSE MELPHALAN, INDUCTION TREATMENT, Female, Autologous, Immunosuppressive Agents, Pyrazine, Human, medicine.drug, MAINTENANCE THERAPY, medicine.medical_specialty, DOXORUBICIN, Antineoplastic Agents, Hormonal, Prognosi, Immunology, Urology, Antineoplastic Agents, dexamethasone, Transplantation, Autologous, Disease-Free Survival, Dexamethasone, Humans, Multiple Myeloma, Cell Biology, medicine, Autologous transplantation, METAANALYSIS, Transplantation, Antineoplastic Combined Chemotherapy Protocol, Hormonal, business.industry, medicine.disease, Surgery, business, Settore MED/15 - Malattie del Sangue
Abstract

In a randomized, phase 3 study, superior complete/near-complete response (CR/nCR) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) versus thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autologous stem cell transplantation for newly diagnosed myeloma patients (intention-to-treat analysis; VTD, n = 236; TD, n = 238). This per-protocol analysis (VTD, n = 160; TD, n = 161) specifically assessed the efficacy and safety of consolidation with VTD or TD. Before starting consolidation, CR/nCR rates were not significantly different in the VTD (63.1%) and TD arms (54.7%). After consolidation, CR (60.6% vs 46.6%) and CR/nCR (73.1% vs 60.9%) rates were significantly higher for VTD-treated versus TD-treated patients. VTD consolidation significantly increased CR and CR/nCR rates, but TD did not (McNemar test). With a median follow-up of 30.4 months from start of consolidation, 3-year progression-free survival was significantly longer for the VTD group (60% vs 48% for TD). Grade 2 or 3 peripheral neuropathy (8.1% vs 2.4%) was more frequent with VTD (grade 3, 0.6%) versus TD consolidation. The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation. VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients randomly assigned to the VTD arm of the study. The study is registered at www.clinicaltrials.gov as #NCT01134484.

Published
2012

88. Different Frequency Classes of Sequences in Heterogeneous Nuclear RNA of Normal Promyelocytes and Lymphoblasts and of Leukemic Blast Cells of Circulating Blood and of the HL60 Line

Author

Torelli, U., Torelli, G., Narni, F., Donelli, A., Ferrari, S., Franchini, G., Calabretta, B., Heimpel, H., editor, Huhn, D., editor, Mueller-Eckhardt, C., editor, Ruhenstroth-Bauer, G., editor, Neth, Rolf, editor, Gallo, Robert C., editor, Graf, Thomas, editor, Mannweiler, Klaus, editor, and Winkler, Kurt, editor

Published
1981
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89. T-cell Interferon-gamma-release assays performance to detect latent tuberculosis infection in immunocompromised patients

Author

Losi, M, Luppi, F, Roversi, P, Ferrara, G, Cerri, S, Ferrari, A, D’Amico, R, Codeluppi, M, Meacci, M, Luppi, M, Torelli, G, Fabbri, L, Richeldi, L, Losi M, Luppi F, Roversi P, Ferrara G, Cerri S, Ferrari A, D’Amico R, Codeluppi M, Meacci M, Luppi M, Torelli G, Fabbri LM, Richeldi L., Losi, M, Luppi, F, Roversi, P, Ferrara, G, Cerri, S, Ferrari, A, D’Amico, R, Codeluppi, M, Meacci, M, Luppi, M, Torelli, G, Fabbri, L, Richeldi, L, Losi M, Luppi F, Roversi P, Ferrara G, Cerri S, Ferrari A, D’Amico R, Codeluppi M, Meacci M, Luppi M, Torelli G, Fabbri LM, and Richeldi L.

Published
2008

90. Efficacy and Safety of Low-Dose Aspirin in Polycythemia Vera

Author

Landolfi, R, Marchioli, R, Kutti, J, Gisslinger, H, Tognoni, G, Patrono, C, Barbui, T, Finazzi, G, Pusterla, S, Falanga, A, Galli, M, Wadenvik, H, Gastl, G, Ludescher, C, Lutz, D, Girschikofsky, M, Michlmayr, G, Rechberger, E, Niessner, H, Ivansich, E, Rain, Jd, Chommienne Thomas, C, Hehlmann, R, Engelich, G, Kohne, E, Kramer, A, Christakis, Ji, Papaioannou, M, Gerotziafas, G, O'Donnell, R, Bennett, M, Lugassy, G, Ellis, M, Eldor, A, Naparstek, E, Marilus, R, Leoni, P, Rupoli, S, Scortechini, Ar, Agostini, V, Volpe, E, Calmieri, F, Volpe, A, Storti, G, Ciampa, A, Dammacco, F, Lauta, Vm, Ranieri, G, Rizzi, R, Orsola, S, Tura, S, Finelli, C, Marino, G, Rossi, G, Almici, C, Capucci, A, Zanetti, F, Giustolisi, R, Cacciola, Rr, Cacciola, E, Peta, A, Magro, D, Frigerio, G, Alberio, F, Beretta, A, Bonferroni, M, Raviolo, A, Ferrini, Prl, Grossi, A, Fabbri, A, Nardelli, S, Centra, A, Musolino, C, Bellomo, G, Trincali, O, Spatari, Giovanna, Foa, P, Gerli, G, Carraro, Mc, Zanella, A, Lurlo, A, Barraco, F, Torelli, G, Marietta, M, Pogliani, E, Miccolis, Ir, La Rocca, A, Puglisi, A, Sardeo, G, Rotoli, B, Martinelli, V, Ciancia, R, Cardarelli, A, Cimino, R, Fasanaro, A, Randi, Ml, Rizzoli, V, Caramatti, C, Gaeta, L, Lazzarino, M, Passamonti, F, Lazzola, M, Malabarba, L, Natale, D, Pulini, S, Davi, G, Gugliotta, L, Ilariucci, F, De Candia, E, Eugenio, S, Amadori, S, Buccisano, F, Mandelli, F, Montefusco, E, Petti, Mc, Spadea, A, Carotenuto, M, Morelli, A, Nobile, M, Longinotti, M, Pardini, Sm, Lauria, F, Buccalossi, A, Gentili, S, Mazza, P, Cervellera, M, Maggi, A, Di Francesco, A, Pasqualoni, E, Chisesi, T, Polacco, A, Capnist, G, Rodeghiero, F, Ruggeri, M, Arrizabalaga, B, Remacha, A, De Mendiguren, Bp, Hernandez Nieto, L, Hernandez Garcia, Mt, Gonzalez Brito, G, Machado, P, Garcia, G, Villegas, A, Pena, A, Fernandez, Ag, Carbonell, F, Del Arco, A, Back, H, Stenke, L, Hansen, S, Larsson, G, Stromblad, G, Lauri, B, Ryden, Bo, Linder, O, Lundholm, Bg, Lannemyr, O, Strandberg, M, Andreasson, B, Stockelberg, D, Pasquariello, F, Tichelli, A, Otremba, B, Hinrichs, Hf, Weber Stadelmann, W, Bareford, D, Oscier, Dg, Bowey, N, Taylor, Pc, de Gaetano, G, Najean, Y, Pearson, Tc, Di Blasio, A, Atashkar, S, Mari, E, Tamayo, D, Borelli, G, Ferri, B, Marfisi, Rm, Olivieri, M, Polidoro, A, Spoltore, R, Levantesi, G, Di Mascio, R, Miceli, G, Sperti, G, Correale, E, Vermjlen, J, and Collins, R.

Subjects
Aspirin, medicine.medical_specialty, business.industry, food and beverages, General Medicine, medicine.disease, Thrombosis, Pulmonary embolism, Venous thrombosis, Polycythemia vera, Relative risk, Internal medicine, Anesthesia, Cardiology, Medicine, Myocardial infarction, business, Contraindication, medicine.drug
Abstract

background The use of aspirin for the prevention of thrombotic complications in polycythemia vera is controversial. methods We enrolled 518 patients with polycythemia vera, no clear indication for aspirin treatment, and no contraindication to such treatment in a double-blind, placebo-controlled, randomized trial to assess the safety and efficacy of prophylaxis with low-dose aspirin (100 mg daily). The two primary end points were the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes. The mean duration of follow-up was about three years. results Treatment with aspirin, as compared with placebo, reduced the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes (relative risk, 0.41; 95 percent confidence interval, 0.15 to 1.15; P=0.09) and the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes (relative risk, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.03). Overall mortality and cardiovascular mortality were not reduced significantly. The incidence of major bleeding episodes was not significantly increased in the aspirin group (relative risk, 1.62; 95 percent confidence interval, 0.27 to 9.71). conclusions Low-dose aspirin can safely prevent thrombotic complications in patients with polycythemia vera who have no contraindications to such treatment.

Published
2004

91. Diagnosis of latent tuberculosis infection in patients with hematological malignancies: use of the new IFN-gamma-based blood tests

Author

Losi, M, Luppi, F, Cerri, S, Ferrari, A, D’Amico, R, Alfieri, P, Roversi, P, Meacci, M, Meccugni, B, Marchetti Dori, I, Pollastri, G, Pederzoli, F, Caracciolo, R, Marasca, R, Luppi, M, Torelli, G, Fabbri, L, Richeldi, L, Losi M, Luppi F, Cerri S, FERRARI, ANDREA, D’Amico R, Alfieri P, Roversi P, Meacci M, Meccugni B, Marchetti Dori I, Pollastri G, Pederzoli F, Caracciolo R, Marasca R, Luppi M, Torelli G, Fabbri LM, Richeldi L, Losi, M, Luppi, F, Cerri, S, Ferrari, A, D’Amico, R, Alfieri, P, Roversi, P, Meacci, M, Meccugni, B, Marchetti Dori, I, Pollastri, G, Pederzoli, F, Caracciolo, R, Marasca, R, Luppi, M, Torelli, G, Fabbri, L, Richeldi, L, Losi M, Luppi F, Cerri S, FERRARI, ANDREA, D’Amico R, Alfieri P, Roversi P, Meacci M, Meccugni B, Marchetti Dori I, Pollastri G, Pederzoli F, Caracciolo R, Marasca R, Luppi M, Torelli G, Fabbri LM, and Richeldi L

Published
2007

93. T-cell Interferon-gamma-release assays performance to detect latent tuberculosis infection in immunocompromised patients

Author

Losi M, Luppi F, Roversi P, Ferrara G, Cerri S, Ferrari A, D’Amico R, Codeluppi M, Meacci M, Luppi M, Torelli G, Fabbri LM, Richeldi L., Losi, M, Luppi, F, Roversi, P, Ferrara, G, Cerri, S, Ferrari, A, D’Amico, R, Codeluppi, M, Meacci, M, Luppi, M, Torelli, G, Fabbri, L, and Richeldi, L

Subjects
T-cell Interferon-gamma-release assays, immunocompromised patients
Published
2008

94. Astrophysical sources of gravitational waves

Author

Caron, B., Dominjon, A., Drezen, C., Flaminio, R., Grave, X., Marion, F., Massonnet, L., Mehmel, C., Morand, R., Mours, B., Yvert, M., Babusci, D., Giordano, G., Matone, G., Mackowski, J. M., Napolitano, M., Pinard, L., Dognin, L., Barone, Fabrizio, Calloni, E., Di Fiore, L., Flagiello, M., Grado, A., Longo, Maurizio, Lops, M., Marano, Stefano, Milano, L., Russo, G., Solimeno, S., Acker, Y., Brillet, A., Bondu, F., Brisson, V., Cavalier, F., Davier, M., Heitmann, H., Hello, P., Jacquemet, M., Latrach, L., Le Diberder, F., Man, C. N., Manh, P. T., Taubmann, M., Vinet, J. Y., Boccara, C., Gleyzes, P. h., Roger, J. P., Loriette, V., Cagnoli, G., Gammaitoni, L., Kovalik, J., Marchesoni, F., Punturo, M., Barsuglia, M., Bernardini, M., Braccini, S., Bradaschia, C., Del Fabbro, R., De Salvo, R., Di Virgilio, A., Ferrante, I., Fidecaro, F., Giassi, A., Giazotto, A., Gorini, G., Holloway, L., Lami, S., Lapenna, P., Losurdo, G., Mancini, S., Morganti, M., Palla, F., Pan, H. B., Passuello, D., Poggiani, R., Torelli, G., Zhang, Z., Majorana, E., Puppo, P., Rapagnani, P., and Ricci, F.

Subjects
Physics, Nuclear and High Energy Physics, Gravitational-wave observatory, Gravitational wave, Astrophysics::High Energy Astrophysical Phenomena, Astrophysics::Instrumentation and Methods for Astrophysics, Astronomy, Astrophysics::Cosmology and Extragalactic Astrophysics, Astrophysics, Gravitational-wave astronomy, Atomic and Molecular Physics, and Optics, LIGO, Gravitational energy, General Relativity and Quantum Cosmology, Neutron star, Gravitational collapse, Astrophysics::Galaxy Astrophysics, Gravitational redshift
Abstract

The interferometric detectors of gravitational waves (GW) (such as VIRGO and LIGO) will search for events in a frequency band within a few Hz and a few kHz, where several sources are expected to emit. In this talk we outline briefly the current theoretical knowledge on the emission of GW in events such as the coalescence of compact binaries, the gravitational collapse, the spinning of a neutron stars. Expected amplitudes are compared with the target sensitivity of the VIRGO/LIGO interferometric detectors.

Published
2000

95. Virgo and interferometer for gravitational wave detection

Author

Caron, B., Dominjon, A., Drezen, C., Flaminio, R., Grave, X., Marion, F., Massonnet, L., Mehmel, C., Morand, R., Mours, B., Yvert, M., Babusci, D., Giordano, G., Matone, G., Mackowski, J. M., Napolitano, M., Pinard, L., Dognin, L., Barone, Fabrizio, Calloni, E., Di Fiore, L., Flagiello, M., Grado, A., Longo, Maurizio, Lops, M., Marano, Stefano, Milano, L., Russo, G., Solimeno, S., Acker, Y., Brillet, A., Bondu, F., Brisson, V., Cavalier, F., Davier, M., Heitmann, H., Hello, P., Jacquemet, M., Latrach, L., Le Diberder, F., Man, C. N., Manh, P. T., Taubmann, M., Vinet, J. Y., Boccara, C., Gleyzes, P. h., Roger, J. P., Loriette, V., Cagnoli, G., Gammaitoni, L., Kovalik, J., Marchesoni, F., Punturo, M., Barsuglia, M., Bernardini, M., Braccini, S., Bradaschia, C., Del Fabbro, R., De Salvo, R., Di Virgilio, A., Ferrante, I., Fidecaro, F., Giassi, A., Giazotto, A., Gorini, G., Holloway, L., Lami, S., Lapenna, P., Losurdo, G., Mancini, S., Morganti, M., Palla, F., Pan, H. B., Passuello, D., Poggiani, R., Torelli, G., Zhang, Z., Majorana, E., Puppo, P., Rapagnani, P., and Ricci, F.

Subjects
Physics, Nuclear and High Energy Physics, Gravitational wave, Detector, Astrophysics::Instrumentation and Methods for Astrophysics, Physics::Optics, Astronomy, Michelson interferometer, Astrophysics::Cosmology and Extragalactic Astrophysics, Astrophysics, Atomic and Molecular Physics, and Optics, law.invention, General Relativity and Quantum Cosmology, Interferometry, law, Astrophysics::Galaxy Astrophysics, Noise (radio)
Abstract

Gravitational waves propagating from rapidly accelerating star masses can be detected by means of interferometric techniques. The Virgo detector is a Michelson interferometer, with two 3 km long Fabry-Perot cavities, that is going to be built in the countryside of Pisa (Italy). Principles of interferometric gravitational wave detection, and the main noise sources in the Virgo apparatus are treated. The Virgo optical scheme and its main components are also described. Finally, an overview on the status of works at the Virgo site is presented.

Published
2000

96. Diagnosis of latent tuberculosis infection in patients with hematological malignancies: use of the new IFN-gamma-based blood tests

Author

Losi M, Luppi F, Cerri S, FERRARI, ANDREA, D’Amico R, Alfieri P, Roversi P, Meacci M, Meccugni B, Marchetti Dori I, Pollastri G, Pederzoli F, Caracciolo R, Marasca R, Luppi M, Torelli G, Fabbri LM, Richeldi L, Losi, M, Luppi, F, Cerri, S, Ferrari, A, D’Amico, R, Alfieri, P, Roversi, P, Meacci, M, Meccugni, B, Marchetti Dori, I, Pollastri, G, Pederzoli, F, Caracciolo, R, Marasca, R, Luppi, M, Torelli, G, Fabbri, L, and Richeldi, L

Subjects
Latent tuberculosis infection, hematological malignancies, IFN-gamma-based blood tests
Published
2007

100. GENE EXPRESSION PROFILING IN B-CELL CHRONIC LYMPHOCYTIC LEUKAEMIA REVEALS DIFFERENTIAL EXPRESSION LEVELS OF EDAG AND ANGIOPOIETIN-2 GENES BETWEEN UNMUTATED AND MUTATED PATIENTS

Author

Maffei R., Marasca R., Severini C., Semeria A., Zucchini P., Ferrari A., Santachiara R., Villani M., Castelli I., Martinelli S., Morselli M., Fontana M., Serra R., Torelli G., MORANDI, ELENA, SILINGARDI, PAOLA, COLACCI, ANNAMARIA, Maffei R., Marasca R., Morandi E., Severini C., Semeria A., Silingardi P., Zucchini P., Ferrari A., Santachiara R., Villani M., Castelli I., Martinelli S., Morselli M., Fontana M., Colacci A., Serra R., and Torelli G.

Subjects
hemic and lymphatic diseases, B-CELL CHRONIC LYMPHOCYTIC LEUKAEMIA, GENE EXPRESSION PROFILING
Abstract

B-cell chronic lymphocytic leukemia (B-CLL) shows a high heterogeneity in the clinical course, spanning from aggressive to completely indolent behaviour. To identify the correspondent gene expression variability, we selected 29 well-defined, newly diagnosed B-CLL patients and we hybridized them on ink-jet printed microarrays comprising about 20,000 oligonucleotide probes. The mutational status of IgVH genes was examined in all 29 CLL cases. Using the classical homology cut off value of 98%, 14 patients (48.3%) had mutated VH genes (M-CLL group) and 15 (51.7%) had unmutated VH sequences (UM-CLL group). As previously reported, different immunoglobulin gene se ments revealed a biased usage related to the mutational immunoglobulin VH gene and poor prognosis was associated with the unmutated subset. Firstly, using 4 different unsupervised clustering algorithms to analyze gene expression data, we identified two robust CLL clusters. Altered expression of genes mainly involved in protein biosynthesis and oxidative phosphorylation differentiated the two main CLL subgroups. These B-CLL biological clusters were not associated with Ig mutational status. Furthermore, we applied another unsupervised algorithm after the exclusion of the genes characterizing the previously identified CLL subsets identifying two new CLL clusters, showing a clear association to the Ig mutational status. In order to identify how the immunoglobulin status could affect the levels of specific genes, we applied supervised clustering based on differences in the IgVH mutation status. Differentially regulated genes were revealed at a significant level of 0.01, yielding 128 genes. Of note, we observed in unmutated CLL cases a down-regulation of genes belonging to B-cell- and antibody-mediated immunity and immunity/defence categories. Moreover, genes involved in Wnt signalling, integrin signalling, inflammation mediated by chemokine and cytokine signalling pathways as well as in T cell activation were found down-regulated in unmutated CLLs. The analysis identified EDAG as the best discriminating gene between M- and UMCLLs. Interestingly, EDAG regulates the proliferation and differentiation of hematopoietic cells and apoptosis resistance through the activation of NF-k B. Again, we found the high expression in UM-CLL of angiopoietin 2 (ANGPT2), inducer of angiogenesis. We evaluated the mRNA levels of EDAG and ANGPT2 in a large cohort of both unpurified and CD19+ purified CLL samples as well as in some cases of LMA, LLA, LMC and in normal PBMCs and CD19+ selected cells, using Real-Time PCR. Then, we analyzed the correlation between EDAG and ANGPT2 mRNA levels as well as their association with immunoglobulin mutational status, haematological parameters and clinical outcome of patients. PO-060

Published
2006

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