21 results on '"Fontani, L."'
Search Results
2. Mek1 inhibition in vivo mitigates progressive cardiac concentric hypertrophy promoted by activated Met receptor
- Author
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Sala, V., primary, Gallo, S., additional, Gatti, S., additional, Medico, E., additional, Vigna, E., additional, Cantarella, D., additional, Fontani, L., additional, Natale, M., additional, Morello, M., additional, Ponzetto, A., additional, and Crepaldi, T., additional
- Published
- 2015
- Full Text
- View/download PDF
3. u201cActive\u201d cancer immunotherapy by anti-Met antibody gene transfer
- Author
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Vigna E, Pacchiana G, Mazzone M, Chiriaco C, Fontani L, Basilico C, Pennacchietti S, and Comoglio PM
- Published
- 2008
4. Anatomy of carbonate turbidite mega-beds (M. Cassio Formation, Upper Cretaceous, northern Apennines, Italy)
- Author
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Zuffa, G. G., Fontana, Daniela, Morlotti, E., PREMOLI SILVA, I., Sighinolfi, G. P., and Stefani, C. FONTANI L.
- Subjects
helminthoid Flysch ,carbonate turbidites ,Mega-beds - Published
- 2003
5. On board processing procedures for the Solar Orbiter METIS coronagraph
- Author
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Pancrazzi, M., primary, Focardi, M., additional, Uslenghi, M., additional, Magli, E., additional, Ricci, M., additional, Bemporad, A., additional, Nicolini, G., additional, Landini, F., additional, Romoli, M., additional, Antonucci, E., additional, Fineschi, S., additional, Naletto, G., additional, Nicolosi, P., additional, Spadaro, D., additional, Andretta, V., additional, Errico, W., additional, Bigongiari, F., additional, Fontani, L., additional, Orlandi, M., additional, and Colonna, A., additional
- Published
- 2013
- Full Text
- View/download PDF
6. Recent advances in electronics and software for the METIS coronagraph aboard solar orbiter
- Author
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Focardi, M., primary, Pancrazzi, M., additional, Nicolini, G., additional, Magli, E., additional, Ricci, M., additional, Uslenghi, M., additional, Romoli, M., additional, Landini, F., additional, Antonucci, E., additional, Fineschi, S., additional, Naletto, G., additional, Nicolosi, P., additional, Spadaro, D., additional, Andretta, V., additional, Errico, W., additional, Bigongiari, F., additional, Fontani, L., additional, Orlandi, Marco, additional, and Colonna, Annamaria, additional
- Published
- 2013
- Full Text
- View/download PDF
7. Primary breast cancer stem-like cells metastasise to bone, switch phenotype and acquire a bone tropism signature
- Author
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D′Amico, L, primary, Patanè, S, additional, Grange, C, additional, Bussolati, B, additional, Isella, C, additional, Fontani, L, additional, Godio, L, additional, Cilli, M, additional, D′Amelio, P, additional, Isaia, G, additional, Medico, E, additional, Ferracini, R, additional, and Roato, I, additional
- Published
- 2013
- Full Text
- View/download PDF
8. Power supply system for the tracker detector of the AMS experiment
- Author
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Menichelli, M, Battiston, R, Bizzarri, M, Checcucci, B, Castellini, G, Bakki, P, Banfalvi, A, Blasko, S, Gschwindt, A, Szabó, J, Fontani, L, and Pasuello, G
- Subjects
Detectors and Experimental Techniques - Published
- 1996
9. Poster Session 3: Friday 9 December 2011, 08:30-12:30 * Location: Poster Area
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Kenny, C., primary, Adhya, S., additional, Dworakowski, R., additional, Brickham, B., additional, Maccarthy, P., additional, Monaghan, M., additional, Guzzo, A., additional, Innocenti, F., additional, Vicidomini, S., additional, Lazzeretti, D., additional, Squarciotta, S., additional, De Villa, E., additional, Donnini, C., additional, Bulletti, F., additional, Guerrini, E., additional, Pini, R., additional, Bendjelid, K., additional, Viale, J., additional, Duperret, S., additional, Piriou, V., additional, Jacques, D., additional, Shahgaldi, K., additional, Silva, C., additional, Pedro, F., additional, Deister, L., additional, Brodin, L.-A., additional, Sahlen, A., additional, Manouras, A., additional, Winter, R., additional, Berjeb, N., additional, Cimadevilla, C., additional, Dreyfus, J., additional, Cueff, C., additional, Malanca, M., additional, Chiampan, A., additional, Vahanian, A., additional, Messika-Zeitoun, D., additional, Muraru, D., additional, Peluso, D., additional, Dal Bianco, L., additional, Beraldo, M., additional, Solda', E., additional, Tuveri, M., additional, Cucchini, U., additional, Al Mamary, A., additional, Badano, L., additional, Iliceto, S., additional, Almuntaser, I., additional, King, G., additional, Norris, S., additional, Daly, C., additional, Ellis, E., additional, Murphy, R., additional, Erdei, T., additional, Denes, M., additional, Kardos, A., additional, Foldesi, C., additional, Temesvari, A., additional, Lengyel, M., additional, Bouzas Mosquera, A., additional, Broullon, F., additional, Alvarez-Garcia, N., additional, Peteiro, J., additional, Barge-Caballero, G., additional, Lopez-Perez, M., additional, Lopez-Sainz, A., additional, Castro-Beiras, A., additional, Luotolahti, M., additional, Luotolahti, H., additional, Kantola, I., additional, Viikari, J., additional, Andersen, M., additional, Ersboell, M., additional, Bro-Jeppesen, J., additional, Gustafsson, F., additional, Koeber, L., additional, Hassager, C., additional, Moller, J., additional, Coisne, D., additional, Diakov, C., additional, Vallet, F., additional, Lequeux, B., additional, Blouin, P., additional, Christiaens, L., additional, Esposito, R., additional, Santoro, A., additional, Schiano Lomoriello, V., additional, Raia, R., additional, Santoro, C., additional, De Simone, G., additional, Galderisi, M., additional, Abdula, G., additional, Kosmala, W., additional, Szczepanik-Osadnik, H., additional, Przewlocka-Kosmala, M., additional, Mysiak, A., additional, O' Moore-Sullivan, T., additional, Marwick, T., additional, Tan, Y. T., additional, Wenzelburger, F., additional, Leyva, F., additional, Sanderson, J., additional, Pichler, P., additional, Syeda, B., additional, Hoefer, P., additional, Zuckermann, A., additional, Binder, T., additional, Fijalkowski, M., additional, Koprowski, A., additional, Galaska, R., additional, Blaut, K., additional, Sworczak, K., additional, Rynkiewicz, A., additional, Lee, S., additional, Kim, W., additional, Jung, L., additional, Yun, H., additional, Song, M., additional, Ko, J., additional, Khalifa, E. A., additional, Szymanski, P., additional, Lipczynska, M., additional, Klisieiwcz, A., additional, Hoffman, P., additional, Jorge, C., additional, Silva Marques, J., additional, Robalo Martins, S., additional, Calisto, C., additional, Mieiro, M., additional, Vieira, S., additional, Correia, M., additional, Carvalho De Sousa, J., additional, Almeida, A., additional, Nunes Diogo, A., additional, Park, C., additional, March, K., additional, Tillin, T., additional, Mayet, J., additional, Chaturvedi, N., additional, Hughes, A., additional, Di Bello, V., additional, Giannini, C., additional, Delle Donne, M., additional, De Sanctis, F., additional, Spontoni, P., additional, Cucco, C., additional, Corciu, A., additional, Grigoratos, C., additional, Bogazzi, F., additional, Balbarini, A., additional, Enescu, O., additional, Suran, B., additional, Florescu, M., additional, Cinteza, M., additional, Vinereanu, D., additional, Higuchi, Y., additional, Iwakura, K., additional, Okamura, A., additional, Date, M., additional, Fujii, K., additional, Cortez-Dias, N., additional, Silva, D., additional, Carrilho-Ferreira, P., additional, Magalhaes, A., additional, Ribeiro, S., additional, Goncalves, S., additional, Fiuza, M., additional, Pinto, F., additional, Placido, R., additional, Bordalo, A., additional, Grzywocz, P., additional, Mizia-Stec, K., additional, Chudek, J., additional, Gasior, Z., additional, Maceira Gonzalez, A. M., additional, Cosin Sales, J., additional, Dalli, E., additional, Igual, B., additional, Diago, J., additional, Aguilar, J., additional, Ruvira, J., additional, Cimino, S., additional, Pedrizzetti, G., additional, Tonti, G., additional, Canali, E., additional, Petronilli, V., additional, Boccalini, F., additional, Mattatelli, A., additional, Hiramoto, Y., additional, Iacoboni, C., additional, Agati, L., additional, Trifunovic, D., additional, Ostojic, M., additional, Vujisic-Tesic, B., additional, Petrovic, M., additional, Nedeljkovic, I., additional, Banovic, M., additional, Boricic-Kostic, M., additional, Draganic, G., additional, Tesic, M., additional, Gavina, C., additional, Lopes, R., additional, Lourenco, A., additional, Almeida, J., additional, Rodrigues, J., additional, Pinho, P., additional, Zamorano, J., additional, Leite-Moreira, A., additional, Rocha-Goncalves, F., additional, Clavel, M.-A., additional, Capoulade, R., additional, Dumesnil, J., additional, Mathieu, P., additional, Despres, J.-P., additional, Pibarot, P., additional, Bull, S., additional, Pitcher, A., additional, Augustine, D., additional, D'arcy, J., additional, Karamitsos, T., additional, Rai, A., additional, Prendergast, B., additional, Becher, H., additional, Neubauer, S., additional, Myerson, S., additional, Magne, J., additional, Donal, E., additional, Davin, L., additional, O'connor, K., additional, Pirlet, C., additional, Rosca, M., additional, Szymanski, C., additional, Cosyns, B., additional, Pierard, L., additional, Lancellotti, P., additional, Calin, A., additional, Popescu, B., additional, Beladan, C., additional, Enache, R., additional, Lupascu, L., additional, Sandu, C., additional, Ginghina, C., additional, Kamperidis, V., additional, Hadjimiltiadis, S., additional, Sianos, G., additional, Anastasiadis, K., additional, Grosomanidis, V., additional, Efthimiadis, G., additional, Karvounis, H., additional, Parharidis, G., additional, Styliadis, I., additional, Gonzalez Canovas, C., additional, Munoz-Esparza, C., additional, Bonaque Gonzalez, J., additional, Fernandez, A., additional, Salar Alcaraz, M., additional, Saura Espin, D., additional, Pinar Bermudez, E., additional, Oliva-Sandoval, M., additional, De La Morena Valenzuela, G., additional, Valdes Chavarri, M., additional, Brochet, E., additional, Lepage, L., additional, Attias, D., additional, Detaint, D., additional, Himbert, D., additional, Iung, B., additional, Pirat, B., additional, Little, S., additional, Chang, S., additional, Tiller, L., additional, Kumar, R., additional, Zoghbi, W., additional, Lee, A. P.-W., additional, Hsiung, M., additional, Wan, S., additional, Wong, R., additional, Luo, F., additional, Fang, F., additional, Xie, J., additional, Underwood, M., additional, Sun, J., additional, Yu, C., additional, Jansen, R., additional, Tietge, W., additional, Sijbrandij, K., additional, Cramer, M., additional, De Heer, L., additional, Kluin, J., additional, Chamuleau, S. A. J., additional, Oliveras Vila, T., additional, Ferrer Sistach, E., additional, Delgado Ramis, L., additional, Lopez Ayerbe, J., additional, Vallejo Camazon, N., additional, Gual Capllonch, F., additional, Garcia Alonso, C., additional, Teis Soley, A., additional, Ruyra Baliarda, X., additional, Bayes Genis, A., additional, Negrea, S., additional, Alexandrescu, C., additional, Bourlon, F., additional, Civaia, F., additional, Dreyfus, G., additional, Paetzold, S., additional, Luha, O., additional, Hoedl, R., additional, Stoschitzky, G., additional, Pfeiffer, K., additional, Zweiker, D., additional, Pieske, B., additional, Maier, R., additional, Sevilla, T., additional, Revilla, A., additional, Lopez, J., additional, Vilacosta, I., additional, Arnold, R., additional, Gomez, I., additional, San Roman, J., additional, Nikcevic, G., additional, Djordjevic Dikic, A., additional, Djordjevic, S., additional, Raspopovic, S., additional, Jovanovic, V., additional, Kircanski, B., additional, Pavlovic, S., additional, Milasinovic, G., additional, Ruiz-Zamora, I., additional, Cabrera Bueno, F., additional, Molina, M., additional, Fernandez-Pastor, J., additional, Pena, J., additional, Linde, A., additional, Barrera, A., additional, Alzueta, J., additional, Bremont, C., additional, Bensaid, A., additional, Alonso, H., additional, Zaghden, O., additional, Nahum, J., additional, Dubois-Rande, J., additional, Gueret, P., additional, Lim, P., additional, Lee, S.-P., additional, Park, K., additional, Kim, H.-R., additional, Lee, J.-H., additional, Ahn, H.-S., additional, Kim, J.-H., additional, Kim, H.-K., additional, Kim, Y.-J., additional, Sohn, D.-W., additional, Niemann, M., additional, Herrmann, S., additional, Hu, K., additional, Liu, D., additional, Beer, M., additional, Ertl, G., additional, Wanner, C., additional, Takenaka, T., additional, Tei, C., additional, Weidemann, F., additional, Madeira, H., additional, Mendes Pedro, M., additional, Brito, D., additional, Ippolito, R., additional, De Palma, D., additional, Gati, S., additional, Oxborough, D., additional, Reed, M., additional, Zaidi, A., additional, Ghani, S., additional, Sheikh, N., additional, Papadakis, M., additional, Sharma, S., additional, Chow, V., additional, Ng, A., additional, Pasqualon, T., additional, Zhao, W., additional, Hanzek, D., additional, Chung, T., additional, Yeoh, T., additional, Kritharides, L., additional, Magda, L., additional, Mihalcea, D., additional, Jinga, D., additional, Mincu, R., additional, Ferrazzi, E., additional, Segato, G., additional, Folino, F., additional, Famoso, G., additional, Senzolo, M., additional, Bellu, R., additional, Corbetti, F., additional, Tona, F., additional, Azevedo, O., additional, Quelhas, I., additional, Guardado, J., additional, Fernandes, M., additional, Pereira, V., additional, Medeiros, R., additional, Sousa, P., additional, Santos, W., additional, Pereira, S., additional, Marques, N., additional, Mimoso, J., additional, Marques, V., additional, Jesus, I., additional, Rustad, L., additional, Nytroen, K., additional, Gullestad, L., additional, Amundsen, B., additional, Aakhus, S., additional, Linhartova, K., additional, Sterbakova, G., additional, Necas, J., additional, Kovalova, S., additional, Cerbak, R., additional, Nelassov, N., additional, Korotkijan, N., additional, Shishkina, A., additional, Gagieva, B., additional, Nagaplev, M., additional, Eroshenko, O., additional, Morgunov, M., additional, Parmon, S., additional, Velthuis, S., additional, Van Gent, M., additional, Post, M., additional, Westermann, C., additional, Mager, J., additional, Snijder, R., additional, Koyalakonda, S. P., additional, Anderson, M., additional, Burgess, M., additional, Bergenzaun, L., additional, Chew, M., additional, Ohlin, H., additional, Gjerdalen, G. F., additional, Hisdal, J., additional, Solberg, E., additional, Andersen, T., additional, Radunovic, Z., additional, Steine, K., additional, Rutz, T., additional, Kuehn, A., additional, Petzuch, K., additional, Pekala, M., additional, Elmenhorst, J., additional, Fratz, S., additional, Mueller, J., additional, Hager, A., additional, Hess, J., additional, Vogt, M., additional, Van Der Linde, D., additional, Van De Laar, I., additional, Wessels, M., additional, Bekkers, J., additional, Moelker, A., additional, Tanghe, H., additional, Van Kooten, F., additional, Oldenburg, R., additional, Bertoli-Avella, A., additional, Roos-Hesselink, J., additional, Cresti, A., additional, Fontani, L., additional, Calabria, P., additional, Capati, E., additional, Severi, S., additional, Lynch, M., additional, Saraf, S., additional, Sandler, B., additional, Yoon, S., additional, Kim, S., additional, Ko, C., additional, Ryu, S., additional, Byun, Y., additional, Seo, H., additional, Ciampi, Q., additional, Rigo, F., additional, Pratali, L., additional, Gherardi, S., additional, Villari, B., additional, Picano, E., additional, Sicari, R., additional, Celutkiene, J., additional, Zakarkaite, D., additional, Skorniakov, V., additional, Zvironaite, V., additional, Grabauskiene, V., additional, Sinicyna, J., additional, Gruodyte, G., additional, Janonyte, K., additional, Laucevicius, A., additional, O'driscoll, J., additional, Schmid, K., additional, Marciniak, A., additional, Saha, A., additional, Gupta, S., additional, Smith, R., additional, Sharma, R., additional, Alvarez Garcia, N., additional, Prada, O., additional, Rodriguez Vilela, A., additional, Barge Caballero, G., additional, Lopez Perez, M., additional, Lopez Sainz, A., additional, Castro Beiras, A., additional, Kochanowski, J., additional, Scislo, P., additional, Piatkowski, R., additional, Grabowski, M., additional, Marchel, M., additional, Roik, M., additional, Kosior, D., additional, Opolski, G., additional, Van De Heyning, C. M., additional, Mahjoub, H., additional, Clausen, H., additional, Basaggianis, C., additional, Newton, J., additional, Del Pasqua, A., additional, Carotti, A., additional, Di Carlo, D., additional, Cetrano, E., additional, Toscano, A., additional, Iacobelli, R., additional, Esposito, C., additional, Chinali, M., additional, Pongiglione, G., additional, Rinelli, G., additional, Larsson, M., additional, Bjallmark, A., additional, Caidahl, K., additional, Brodin, L., additional, Gao, H., additional, Lugiez, M., additional, Guivier, C., additional, Rieu, R., additional, D'hooge, J., additional, Hang, G., additional, Guerin, C., additional, Menard, M., additional, Voigt, J.-U., additional, Dungu, J., additional, Campos, G., additional, Jaffarulla, R., additional, Gomes-Pereira, S., additional, Sutaria, N., additional, Baker, C., additional, Nihoyannopoulos, P., additional, Bellamy, M., additional, Harries, D., additional, Walker, N., additional, Pearson, P., additional, Reiken, J., additional, Batteson, J., additional, Kamdar, R., additional, Murgatroyd, F., additional, D'andrea, A., additional, Riegler, L., additional, Scarafile, R., additional, Pezzullo, E., additional, Salerno, G., additional, Bossone, E., additional, Limongelli, G., additional, Russo, M., additional, Pacileo, G., additional, Calabro', R., additional, Kang, Y., additional, Cui, J., additional, Chen, H., additional, Pan, C., additional, Shu, X., additional, Kiotsekoglou, A., additional, Saha, S., additional, Toole, R., additional, Govind, S., additional, Gopal, A., additional, Crispi, F., additional, Bijnens, B., additional, Sepulveda-Swatson, E., additional, Rojas-Benavente, J., additional, Dominguez, J., additional, Illa, M., additional, Eixarch, E., additional, Sitges, M., additional, Gratacos, E., additional, Prinz, C., additional, Faludi, R., additional, Walker, A., additional, Amzulescu, M., additional, Uejima, T., additional, Fraser, A., additional, Voigt, J., additional, Esmaeilzadeh, M., additional, Maleki, M., additional, Amin, A., additional, Vakilian, F., additional, Noohi, F., additional, Ojaghi Haghighi, Z., additional, Nakhostin Davari, P., additional, Bakhshandeh Abkenar, H., additional, Rimbas, R., additional, Dulgheru, R., additional, Margulescu, A., additional, D' Asaro, M., additional, Mizzon, C., additional, Parisi, F., additional, Jung, B.-C., additional, Lee, B.-Y., additional, Kang, H.-J., additional, Kim, M., additional, Kim, Y., additional, Cho, D., additional, Park, S., additional, Hong, S., additional, Lim, D., additional, Shim, W., additional, Bellsham-Revell, H., additional, Tibby, S., additional, Bell, A. J., additional, Miller, O. I., additional, Greil, G., additional, Simpson, J. M., additional, Providencia, R. A., additional, Trigo, J., additional, Botelho, A., additional, Gomes, P., additional, Seca, L., additional, Barra, S., additional, Faustino, A., additional, Costa, G., additional, Quintal, N., additional, Leitao-Marques, A., additional, Nestaas, E., additional, Stoylen, A., additional, Fugelseth, D., additional, Mornos, C., additional, Ionac, A., additional, Petrescu, L., additional, Cozma, D., additional, Dragulescu, D., additional, Mornos, A., additional, Pescariu, S., additional, Fontana, A., additional, Abbate, M., additional, Cazzaniga, M., additional, Giannattasio, C., additional, Trocino, G., additional, Laser, K., additional, Faber, L., additional, Fischer, M., additional, Koerperich, H., additional, Kececioglu, D., additional, Elnoamany, M. F., additional, Dawood, A., additional, Elhabashy, M., additional, Khalil, Y., additional, Piriou, N., additional, Warin-Fresse, K., additional, Caza, M., additional, Fau, G., additional, Crochet, D., additional, Xhabija, N., additional, Allajbeu, I., additional, Petrela, E., additional, Heba, M., additional, Barreiro Perez, M., additional, Martin Fernandez, M., additional, Renilla Gonzalez, A., additional, Florez Munoz, J., additional, Fernandez Cimadevilla, O., additional, Alvarez Pichel, I., additional, Velasco Alonso, E., additional, Leon Duran, D., additional, Benito Martin, E., additional, Secades Gonzalez, S., additional, Gargani, L., additional, Pang, P., additional, Davis, E., additional, Schumacher, A., additional, Silva Ferreira, A., additional, Bettencourt, N., additional, Matos, P., additional, Oliveira, L., additional, Cosin-Sales, J., additional, Lopez Lereu, M., additional, Monmeneu, J., additional, Estornell, J., additional, Tsverava, M., additional, Tsverava, D., additional, Varela, A., additional, Salagianni, M., additional, Galani, I., additional, Andreakos, E., additional, Davos, C., additional, Ikonomidis, I., additional, Lekakis, J., additional, Tritakis, V., additional, Kadoglou, N., additional, Papadakis, J., additional, Trivilou, P., additional, Tzortzis, S., additional, Koukoulis, C., additional, Paraskevaidis, I., additional, Anastasiou-Nana, M., additional, Kim, G., additional, Youn, H., additional, Ibrahimi, P., additional, Bajraktari, G., additional, Jashari, F., additional, Ahmeti, A., additional, Poniku, A., additional, Haliti, E., additional, Henein, M., additional, Pezo Nikolic, B., additional, Jurin, H., additional, Lovric, D., additional, Baricevic, Z., additional, Ivanac Vranesic, I., additional, Lovric Bencic, M., additional, Ernst, A., additional, and Separovic Hanzevacki, J., additional
- Published
- 2011
- Full Text
- View/download PDF
10. Recent advances in electronics and software for the METIS coronagraph aboard solar orbiter
- Author
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Fineschi, Silvano, Fennelly, Judy, Focardi, M., Pancrazzi, M., Nicolini, G., Magli, E., Ricci, M., Uslenghi, M., Romoli, M., Landini, F., Antonucci, E., Fineschi, S., Naletto, G., Nicolosi, P., Spadaro, D., Andretta, V., Errico, W., Bigongiari, F., Fontani, L., Orlandi, Marco, and Colonna, Annamaria
- Published
- 2013
- Full Text
- View/download PDF
11. The AMS brick: an hv power supply for the space experiment AMS-02
- Author
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Cervelli, F., primary, Incagli, M., additional, Spinella, F., additional, Pilo, F., additional, Venanzoni, G., additional, Pedreschi, E., additional, DiFalco, S., additional, Galeotti, S., additional, Piendibene, M., additional, Avanzini, C., additional, Gherarducci, F., additional, Fausto, G., additional, Castellini, G., additional, Casadei, D., additional, Palmonari, F., additional, Sbarra, C., additional, Marin, J., additional, Berdugo, J., additional, Petroni, F., additional, D'Argliano, S., additional, Fontani, L., additional, Puccini, A., additional, Capell, M., additional, Lebedev, A., additional, and Ambrosi, G., additional
- Full Text
- View/download PDF
12. Power supply design for the tracker detector of the AMS experiment.
- Author
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Menichelli, M., Battiston, R., Bizzarri, M., Checcucci, B., Castellini, G., Bakki, P., Banfalvi, A., Blasko, S., Gschwindt, A., Szabo, J., Fontani, L., and Pasuello, G.
- Published
- 1997
- Full Text
- View/download PDF
13. On board processing procedures for the Solar Orbiter METIS coronagraph
- Author
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Bruzzone, Lorenzo, Pancrazzi, M., Focardi, M., Uslenghi, M., Magli, E., Ricci, M., Bemporad, A., Nicolini, G., Landini, Federico, Romoli, M., Antonucci, E., Fineschi, S., Naletto, Giampiero, Nicolosi, P., Spadaro, D., Andretta, V., Errico, W., Bigongiari, F., Fontani, L., Orlandi, M., and Colonna, A.
- Published
- 2013
- Full Text
- View/download PDF
14. Efficacy of CAR-T immunotherapy in MET overexpressing tumors not eligible for anti-MET targeted therapy.
- Author
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Chiriaco C, Donini C, Cortese M, Ughetto S, Modica C, Martinelli I, Proment A, Vitali L, Fontani L, Casucci M, Comoglio PM, Giordano S, Sangiolo D, Leuci V, and Vigna E
- Subjects
- Humans, Mice, Animals, Immunotherapy, T-Lymphocytes, Cell Line, Tumor, Heterografts, Xenograft Model Antitumor Assays, Receptors, Chimeric Antigen
- Abstract
Background: Aberrant activation of the MET receptor in cancer is sustained by genetic alterations or, more frequently, by transcriptional upregulations. A fraction of MET-amplified or mutated tumors are sensible to MET targeting agents, but their responsiveness is typically short-lasting, as secondary resistance eventually occurs. Since in the absence of genetic alterations MET is usually not a tumor driver, MET overexpressing tumors are not/poorly responsive to MET targeted therapies. Consequently, the vast majority of tumors exhibiting MET activation still represent an unmet medical need., Methods: Here we propose an immunotherapy strategy based on T lymphocytes expressing a Chimeric Antigen Receptor (CAR) targeting MET overexpressing tumors of different histotypes. We engineered two different MET-CAR constructs and tested MET-CAR-T cell cytotoxic activity against different MET overexpressing models, including tumor cell lines, primary cancer cells, organoids, and xenografts in immune-deficient mice., Results: We proved that MET-CAR-T exerted a specific cytotoxic activity against MET expressing cells. Cell killing was proportional to the level of MET expressed on the cell surface. While CAR-T cytotoxicity was minimal versus cells carrying MET at physiological levels, essentially sparing normal cells, the activity versus MET overexpressing tumors was robust, significantly controlling tumor cell growth in vitro and in vivo. Notably, MET-CAR-T cells were also able to brake acquired resistance to MET targeting agents in MET amplified cancer cells carrying secondary mutations in downstream signal transducers., Conclusions: We set and validated at the pre-clinical level a MET-CAR immunotherapy strategy potentially beneficial for cancers not eligible for MET targeted therapy with inhibitory molecules, including those exhibiting primary or secondary resistance., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
15. Dual Constant Domain-Fab: A novel strategy to improve half-life and potency of a Met therapeutic antibody.
- Author
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Cignetto S, Modica C, Chiriaco C, Fontani L, Milla P, Michieli P, Comoglio PM, and Vigna E
- Subjects
- A549 Cells, Animals, Antibodies, Monoclonal blood, Antibodies, Monoclonal chemistry, Antibodies, Monoclonal pharmacology, Antineoplastic Agents blood, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Cell Line, Tumor, Colon metabolism, Colon pathology, Colonic Neoplasms metabolism, Colonic Neoplasms pathology, Female, HEK293 Cells, Half-Life, Humans, Immunoglobulin Fab Fragments blood, Immunoglobulin Fab Fragments chemistry, Immunoglobulin Fab Fragments pharmacology, Mice, Inbred NOD, Mice, SCID, Phosphorylation drug effects, Protein Domains, Protein Engineering, Proto-Oncogene Proteins c-met metabolism, Signal Transduction drug effects, Antibodies, Monoclonal therapeutic use, Antineoplastic Agents therapeutic use, Colon drug effects, Colonic Neoplasms drug therapy, Immunoglobulin Fab Fragments therapeutic use, Proto-Oncogene Proteins c-met antagonists & inhibitors
- Abstract
The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. The chimeric monovalent Fab fragment of the DN30 monoclonal antibody (MvDN30) has an odd mechanism of action, based on cell surface removal of Met via activation of specific plasma membrane proteases. However, the short half-life of the Fab, due to its low molecular weight, is a severe limitation for the deployment in therapy. This issue was addressed by increasing the Fab molecular weight above the glomerular filtration threshold through the duplication of the constant domains, in tandem (DCD-1) or reciprocally swapped (DCD-2). The two newly engineered molecules showed biochemical properties comparable to the original MvDN30 in vitro, acting as full Met antagonists, impairing Met phosphorylation and activation of downstream signaling pathways. As a consequence, Met-mediated biological responses were inhibited, including anchorage-dependent and -independent cell growth. In vivo DCD-1 and DCD-2 showed a pharmacokinetic profile significantly improved over the original MvDN30, doubling the circulating half-life and reducing the clearance. In pre-clinical models of cancer, generated by injection of tumor cells or implant of patient-derived samples, systemic administration of the engineered molecules inhibited the growth of Met-addicted tumors., (Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
16. Cardiac concentric hypertrophy promoted by activated Met receptor is mitigated in vivo by inhibition of Erk1,2 signalling with Pimasertib.
- Author
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Sala V, Gallo S, Gatti S, Medico E, Vigna E, Cantarella D, Fontani L, Natale M, Cimino J, Morello M, Comoglio PM, Ponzetto A, and Crepaldi T
- Subjects
- Animals, Cardiomegaly diagnosis, Cardiomegaly drug therapy, Cardiomegaly genetics, Cell Line, Cytoskeleton metabolism, Disease Models, Animal, Extracellular Matrix metabolism, Gap Junctions metabolism, Gene Expression Regulation, Heart Ventricles metabolism, Heart Ventricles pathology, Mice, Mice, Transgenic, Niacinamide pharmacology, Phenotype, Proto-Oncogene Proteins c-met genetics, Ventricular Remodeling genetics, Cardiomegaly metabolism, MAP Kinase Signaling System drug effects, Niacinamide analogs & derivatives, Protein Kinase Inhibitors pharmacology, Proto-Oncogene Proteins c-met metabolism
- Abstract
Cardiac hypertrophy is a major risk factor for heart failure. Hence, its attenuation represents an important clinical goal. Erk1,2 signalling is pivotal in the cardiac response to stress, suggesting that its inhibition may be a good strategy to revert heart hypertrophy. In this work, we unveiled the events associated with cardiac hypertrophy by means of a transgenic model expressing activated Met receptor. c-Met proto-oncogene encodes for the tyrosine kinase receptor of Hepatocyte growth factor and is a strong inducer of Ras-Raf-Mek-Erk1,2 pathway. We showed that three weeks after the induction of activated Met, the heart presents a remarkable concentric hypertrophy, with no signs of congestive failure and preserved contractility. Cardiac enlargement is accompanied by upregulation of growth-regulating transcription factors, natriuretic peptides, cytoskeletal proteins, and Extracellular Matrix remodelling factors (Timp1 and Pai1). At a later stage, cardiac hypertrophic remodelling results into heart failure with preserved systolic function. Prevention trial by suppressing activated Met showed that cardiac hypertrophy is reversible, and progression to heart failure is prevented. Notably, treatment with Pimasertib, Mek1 inhibitor, attenuates cardiac hypertrophy and remodelling. Our results suggest that modulation of Erk1.2 signalling may constitute a new therapeutic approach for treating cardiac hypertrophies., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
17. Inhibition of ligand-independent constitutive activation of the Met oncogenic receptor by the engineered chemically-modified antibody DN30.
- Author
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Vigna E, Chiriaco C, Cignetto S, Fontani L, Basilico C, Petronzelli F, and Comoglio PM
- Subjects
- Animals, Antibodies, Monoclonal chemistry, Antibodies, Monoclonal pharmacokinetics, Antibodies, Monoclonal pharmacology, Cell Line, Tumor, Female, Humans, Immunoglobulin Fragments chemistry, Immunoglobulin Fragments pharmacology, Immunoglobulin Fragments therapeutic use, Mice, Neoplasms metabolism, Neoplasms pathology, Polyethylene Glycols chemistry, Proto-Oncogene Proteins c-met chemistry, Proto-Oncogene Proteins c-met metabolism, Antibodies, Monoclonal therapeutic use, Neoplasms drug therapy, Proto-Oncogene Proteins c-met antagonists & inhibitors
- Abstract
An awesome number of experimental and clinical evidences indicate that constitutive activation of the Met oncogenic receptor plays a critical role in the progression of cancer toward metastasis and/or resistance to targeted therapies. While mutations are rare, the common mechanism of Met activation is overexpression, either by gene amplification ('addiction') or transcriptional activation ('expedience'). In the first instance ligand-independent kinase activation plays a major role in sustaining the transformed phenotype. Anti-Met antibodies directed against the receptor binding site behave essentially as ligand (Hepatocyte Growth Factor, HGF) antagonists and are ineffective to counteract ligand-independent activation. The monovalent chimeric MvDN30 antibody fragment, PEGylated to extend its half-life, binds the fourth IPT domain and induces 'shedding' of the Met extracellular domain, dramatically reducing both the number of receptors on the surface and their phosphorylation. Downstream signaling is thus inhibited, both in the absence or in the presence of the ligand. In vitro, MvDN30 is a strong inhibitor not only of ligand-dependent invasive growth, sustained by both paracrine and autocrine HGF, but notably, also of ligand-independent growth of 'Met-addicted' cells. In immunocompromised mice, lacking expression of Hepatocyte Growth Factor cross-reacting with the human receptor - thus providing, by definition, a model of 'ligand-independent' Met activation - PEGylated MvDN30 impairs growth of Met 'addicted' human gastric carcinoma cells. In a Met-amplified patient-derived colo-rectal tumor (xenopatient) MvDN30-PEG overcomes the resistance to EGFR targeted therapy (Cetuximab). The PEGylated MvDN30 is thus a strong candidate for targeting tumors sustained by ligand-independent Met oncogenic activation., (Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)
- Published
- 2015
- Full Text
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18. Targeted therapy by gene transfer of a monovalent antibody fragment against the Met oncogenic receptor.
- Author
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Vigna E, Pacchiana G, Chiriaco C, Cignetto S, Fontani L, Michieli P, and Comoglio PM
- Subjects
- Animals, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung metabolism, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung pathology, Cell Line, Tumor, Disease Models, Animal, Female, Gene Expression, Gene Transfer Techniques, Genetic Therapy, Genetic Vectors administration & dosage, Genetic Vectors genetics, Humans, Lentivirus genetics, Lung Neoplasms genetics, Lung Neoplasms metabolism, Lung Neoplasms mortality, Lung Neoplasms pathology, Mice, Proto-Oncogene Proteins c-met antagonists & inhibitors, Transduction, Genetic, Tumor Burden genetics, Xenograft Model Antitumor Assays, Immunoglobulin Fab Fragments genetics, Immunoglobulin Fab Fragments metabolism, Proto-Oncogene Proteins c-met genetics, Proto-Oncogene Proteins c-met metabolism
- Abstract
Unlabelled: Due to the key role played in critical sub-populations, Met is considered a relevant therapeutic target for glioblastoma multiforme and lung cancers. The anti-Met DN30 antibody, engineered to a monovalent Fab (Mv-DN30), proved to be a potent antagonist, inducing physical removal of Met receptor from the cell surface. In this study, we designed a gene therapy approach, challenging Mv-DN30 in preclinical models of Met-driven human glioblastoma and lung carcinoma. Mv-DN30 was delivered by a Tet-inducible-bidirectional lentiviral vector. Gene therapy solved the limitations dictated by the short half-life of the low molecular weight form of the antibody. In vitro, upon doxycycline induction, the transgene: (1) drove synthesis and secretion of the correctly assembled Mv-DN30; (2) triggered the displacement of Met receptor from the surface of target cancer cells; (3) suppressed the Met-mediated invasive growth phenotype. Induction of transgene expression in cancer cells-transplanted either subcutaneously or orthotopically in nude mice-resulted in inhibition of tumor growth. Direct Mv-DN30 gene transfer in nude mice, intra-tumor or systemic, was followed by a therapeutic response. These results provide proof of concept for a gene transfer immunotherapy strategy by a Fab fragment and encourage clinical studies targeting Met-driven cancers with Mv-DN30., Key Message: Gene transfer allows the continuous in vivo production of therapeutic Fab fragments. Mv-DN30 is an excellent tool for the treatment of Met-driven cancers. Mv-DN30 gene therapy represents an innovative route for Met targeting.
- Published
- 2014
- Full Text
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19. Primary breast cancer stem-like cells metastasise to bone, switch phenotype and acquire a bone tropism signature.
- Author
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D'Amico L, Patanè S, Grange C, Bussolati B, Isella C, Fontani L, Godio L, Cilli M, D'Amelio P, Isaia G, Medico E, Ferracini R, and Roato I
- Subjects
- Adult, Animals, Bone Neoplasms genetics, Bone and Bones pathology, Breast Neoplasms genetics, Carcinoma genetics, Female, Gene Expression Regulation, Neoplastic, Genes, Switch genetics, Humans, Mice, Mice, Inbred NOD, Mice, SCID, Neoplastic Stem Cells metabolism, Organ Specificity genetics, Phenotype, Bone Neoplasms secondary, Bone and Bones metabolism, Breast Neoplasms pathology, Carcinoma pathology, Neoplastic Stem Cells pathology, Transcriptome physiology
- Abstract
Background: Bone metastases represent a common and severe complication in breast cancer, and the involvement of cancer stem cells (CSCs) in the promotion of bone metastasis is currently under discussion. Here, we used a human-in-mice model to study bone metastasis formation due to primary breast CSCs-like colonisation., Methods: Primary CD44⁺CD24⁻ breast CSCs-like were transduced by a luciferase-lentiviral vector and injected through subcutaneous and intracardiac (IC) routes in non-obese/severe-combined immunodeficient (NOD/SCID) mice carrying subcutaneous human bone implants. The CSCs-like localisation was monitored by in vivo luciferase imaging. Bone metastatic CSCs-like were analysed through immunohistochemistry and flow cytometry, and gene expression analyses were performed by microarray techniques., Results: Breast CSCs-like colonised the human-implanted bone, resulting in bone remodelling. Bone metastatic lesions were histologically apparent by tumour cell expression of epithelial markers and vimentin. The bone-isolated CSCs-like were CD44⁻CD24⁺ and showed tumorigenic abilities after injection in secondary mice. CD44⁻CD24⁺ CSCs-like displayed a distinct bone tropism signature that was enriched in genes that discriminate bone metastases of breast cancer from metastases at other organs., Conclusion: Breast CSCs-like promote bone metastasis and display a CSCs-like bone tropism signature. This signature has clinical prognostic relevance, because it efficiently discriminates osteotropic breast cancers from tumour metastases at other sites.
- Published
- 2013
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20. "Active" cancer immunotherapy by anti-Met antibody gene transfer.
- Author
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Vigna E, Pacchiana G, Mazzone M, Chiriaco C, Fontani L, Basilico C, Pennacchietti S, and Comoglio PM
- Subjects
- Animals, Antibodies, Monoclonal therapeutic use, Cell Line, Tumor, Female, Gene Transfer Techniques, Genetic Vectors, Humans, Lentivirus genetics, Mice, Neoplasms pathology, Phosphorylation, Proto-Oncogene Proteins c-met, Signal Transduction, Antibodies, Monoclonal genetics, Genetic Therapy, Neoplasms therapy, Proto-Oncogene Proteins antagonists & inhibitors, Receptors, Growth Factor antagonists & inhibitors
- Abstract
Gene therapy provides a still poorly explored opportunity to treat cancer by "active" immunotherapy as it enables the transfer of genes encoding antibodies directed against specific oncogenic proteins. By a bidirectional lentiviral vector, we transferred the cDNA encoding the heavy and light chains of a monoclonal anti-Met antibody (DN-30) to epithelial cancer cells. In vitro, the transduced cells synthesized and secreted correctly assembled antibodies with the expected high affinity, inducing down-regulation of the Met receptor and strong inhibition of the invasive growth response. The inhibitory activity resulted (a) from the interference of the antibody with the Met receptor intracellular processing ("cell autonomous activity," in cis) and (b) from the antibody-induced cleavage of Met expressed at the cell surface ("bystander effect," in trans). The monoclonal antibody gene transferred into live animals by systemic administration or by local intratumor delivery resulted in substantial inhibition of tumor growth. These data provide proof of concept both for targeting the Met receptor and for a gene transfer-based immunotherapy strategy.
- Published
- 2008
- Full Text
- View/download PDF
21. [Neuropsychological aspects of schizophrenic mental deterioration].
- Author
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Roccatagliata G, Arcuri T, Ivaldi M, Fontani L, Maffini M, and Cocito L
- Subjects
- Adult, Female, Humans, Male, Schizotypal Personality Disorder diagnosis, Wechsler Scales, Attention, Intelligence Tests, Schizophrenia diagnosis, Schizophrenic Psychology
- Abstract
The authors have administered a test of intelligence (WAIS) and a test of attention (Color Naming) to a group of patients affected by chronic schizophrenic impairment. The scores give shape to a picture of mental deterioration, especially characterized by a decrease of attentive power. This results validates the possibility of a neuropsychological approach to the etiopatogenesis of schizophrenia and supports the hypothesis that an impairment of mental synthesis power may explain both clinical and psychometric features of the disease.
- Published
- 1979
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