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2. Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study

Author

Auer, Johann, Hubauer, Martin, Pandzic, Sead, Preishuber, Eva, Primus-Grabscheit, Carina, Reitgruber, Dietmar, Schmalzer, Florian, Adlbrecht, Christopher, Schober, Andreas, Hajos, Johannes, Keil, Christoph, Schratter, Alexandra, Frick, Matthias, Benda, Magdalena Anna, Mächler, Maximilian, Mutschlechner, Beatrix, Saely, Christoph, Sprenger, Lukas, Lichtenauer, Michael, Eber, Miriam, Hoppe, Uta, Kolbitsch, Tobias, Jirak, Peter Michael, Mirna, Moritz, Schönbauer, Robert, Bergler-Klein, Jutta, Hengstenberg, Christian, Stojkovic, Stefan, Scherr, Daniel, Manninger-Wünscher, Martin, Rohrer, Ursula, Stühlinger, Markus, Schgoer, Wilfried, Schwarzl, Jana, Pürerfellner, Helmut, Derndorfer, Michael, Ebner, Christian, Eder, Veronika, Kollias, Georgios, Sturmberger, Thomas, Sieghartsleitner, Stefan, Vijgen, Johan, Koopman, Peter, Dujardin, Karl, Anné, Wim, De Ceuninck, Michel, Tavernier, Rene, Duytschaever, Mattias, Knecht, Sébastien, Missault, Luc, Vandekerckhove, Yves, Rossenbacker, Tom, Ector, Bavo, Charlier, Filip, Debruyne, Philippe, Dewilde, Willem, Janssens, Luc, Roosen, John, Vankelecom, Bart, Heidbuchel, Hein, Delesie, Michiel, Vervoort, Gert, Rombouts, Hans, Vanassche, Thomas, Engelen, Matthias, Verhamme, Peter, Willems, Rik, Constance, Christian, Pranno, Nicolas, Cox, Jafna, Bata, Iqbal, Macle, Laurent, Aguilar, Martin, Tourigny, Julia Cadrin, Dubuc, Marc, Dyrda, Katia, Guerra, Peter, Khairy, Paul, Mondésert, Blandine, Rivard, Léna, Roy, Denis, Tadros, Rafik, Talajic, Mario, Thibault, Bernard, Nault, Isabelle, Blier, Louis, Champagne, Jean, Molin, Franck, O'Hara, Gilles, Philippon, François, Plourde, Benoit, Sarrazin, Jean-François, Steinberg, Christian, Coufal, Zdenek, Balazsik, David, Mikulica, Michal, Zapeca, Jakub, Cermak, Ondrej, Drasnar, Tomas, Falc, Matej, Hornof, Josef, Racz, Blazej, Weissova, Danica, Linkova, Hana, Paskova, Eva, Petr, Robert, Sirakova, Andrea, Kettner, Jiri, Benak, Ales, Holek, Martin, Podpera, Ivo, Podperova, Monika, Vancura, Vlastimil, Jandik, Tomas, Smid, Jiri, Dedek, Vratislav, Banik, Jan, Durdil, Vaclav, Hnat, Tomas, Lellouche, Nicolas, Rouffiac, Ségolène, Taldir, Guillaume, Bridonneau, Valentin, Couffon, Philippe, Daudin, Magalie, Hamon, Cécile, Lacaze, Jonathan, Quentin, Anne, Thebault, Christophe, Boiffard, Emmanuel, Billon, Olivier, Miette, Fabien, Pouliquen, Hervé, Turlotte, Guillaume, Gorka, Hervé, Albert, Franck, Bayle, Sandrine, Bensaid, Reda, Dasoveanu, Madalina, Demichili, Thibaud, Dutoiu, Teodora, Khalil, Cliff, Loghin, Caterina, Range, Grégoire, Roussel, Laurent, Socié, Pierre, Thuaire, Christophe, Extramiana, Fabrice, Algalarrondo, Vincent, Boughanmi, Haten, El Mansour, Noreddine, Mohammad, Usman, Sellier, Romain, Elbaz, Meyer, Laperche, Clémence, Maury, Philippe, Kiss, Robert, Borsanyi, Tunde, Gingl, Zoltan, Polgar, Balaza, Benczur, Bela, Bodor, Alexandra, Hepp, Tamas, Malati, Eva, Nagy, Laszlo, Erdei, Norbert, Kapus, Jozsef, Kapus, Katalin, Toth, Brigitta, Matoltsy, Andras, Kiss, Tunde, Merkely, Bela, Herczeg, Szilvia, Kiss, Orsolya, Sallo, Zoltan, Toth, Kalman, Habon, Tamas, Rabai, Miklos, Totsimon, Kinga, Zilahi, Zsolt, Bencze, Gabriella, Santa, Janos, Aradi, Daniel, Kelemen, Barbara, Bolognese, Leonardo, Nesti, Martina, Notarstefano, Pasquale Giovanni, D'Orazio, Simona, Cosmi, Franco, Becattini, Cecilia, Agnelli, Giancarlo, Broccatelli, Belinda, Mosconi, Maria Giulia, Paciaroni, Maurizio, Urbini, Chiara, Parato, Vito Maurizio, Notaristefani, Camilla, Scarano, Michele, Ameri, Pietro, Ghigliotti, Giorgio, Guglielmi, Giulia, Lotti, Roberta, Merlo, Andrea Carlo, Muiesan, Maria Lorenza, Abondio, Andrea, Berasi, Caterina, Mattiuzzo, Elena, Mutti, Claudio, Salvetti, Massimo, Pignatelli, Pasquale, Menichelli, Danilo, Pastori, Daniele, Tamiya, Eiji, Matsumoto, Takahiro, Takabe, Tomosato, Yamamoto, Shoichi, Yamashita, Haruyo, Higashiue, Shinichi, Furuya, Onichi, Hiramatsu, Norihiko, Kasuga, Kensuke, Kojima, Saburo, Komooka, Masatoshi, Kuroyanagi, Satoshi, Matsuura, Makoto, Takemoto, Tetsushi, Yamamoto, Shuji, Saito, Katusmi, Abe, Takuro, Ishida, Issei, Iwanami, Yuji, Kataoka, Shohei, Moriyama, Tetsu, Murohashi, Akira, Sasaki, Akihito, Nakamura, Yuichiro, Ueno, Tetsuya, Shimane, Akira, Hamana, Tomoyo, Ichibori, Hirotoshi, Inoue, Tomohiro, Itoh, Mitsuaki, Iwane, Seigo, Kawai, Hiroya, Kokawa, Tatsuya, Masumoto, Akiko, Matsuo, Koki, Miyata, Taishi, Nakano, Shinsuke, Oishi, Shogo, Onishi, Tetsuari, Sawada, Takahiro, Saito, Takayuki, Shoda, Mitsuhiko, Takahashi, Nobuyuki, Takaya, Tomofumi, Taniguchi, Yasuyo, Tsukamoto, Shota, Tsukishiro, Yasue, Tsukiyama, Yoshiro, Tsunamoto, Hiroshi, Uzu, Kenzo, Yamamoto, Hiroyuki, Yamamoto, Tetsuya, Yokoi, Kiminobu, Yoshida, Chiaki, Watanabe, Nobuhiro, Betsuyaku, Tetsuo, Adachi, Kumiko, Awane, Kouichi, Goto, Daisuke, Sakakibara, Mamoru, Watanabe, Masashi, Ueno, Hideki, Hiroe, Yoshitaka, Matsuo, Koshi, Ayata, Kenji, Fukuda, Ko, Hata, Yoshiki, Hashimoto, Katsushi, Matsumi, Hiroaki, Nikaido, Akira, Okamoto, Shuichi, Sime, Iveta, Stirna, Valters, Reinholde, Ilze, Hansone, Silvija, Kozlovska, Anita, Romanova, Janina, Klincare, Dace, Pontaga, Natalja, Dirmans, Igors, Kalnins, Artis, Upite, Dana, Gersamija, Arcils, Teleznikovs, Arturs, Rozkova, Nadezda, Safro, Jelena, Anguera Camós, Ignasi, Domenico Dallaglio, Paolo, Salguero Bodes, Rafael, Arnbas, Fernando, Borrego, Luis, Marco, Alvaro, Jimenez, Javier Ramos, Gómez-Doblas, Juan José, Pérez Cabeza, Alejandro, Ferreira Gonzålez, Ignacio, Limeres Freire, Javier, Lopez Grau, Merce, Viñolas Prat, Xavier, Moreno Weidmann, Zoraida, Guerra Ramos, Jose Maria, Alonso Martin, Maria Concepcion, Campos Garcia, Bieito, Mogro Carranza, Javier Mauricio, Mendez Zurita, Francisco Javier, Rodriguez Font, Enrique, Gonzales Matos, Carlos Eduardo, García Hernando, Víctor, Lindholm, Carl-Johan, Thulin, Jörgen, Wallén, Håkan, Hagwall, Kristina, Eliasson, Ken, Lundvall, Martin, Olsson, Jens, Kjellman, Björn, Lind, Markus, Johansson, Lars, Svedberg, Niclas, Berglund, Stefan, Söderberg, Julia, Zedigh, Christer, Mooe, Thomas, Axelsson, Mattias, Binsell, Emil, Huber, Daniel, Müller, Christian, Danier, Isabelle, Kühne, Michael, Okamura, Bernhard, Schoepfer, Hadrien, Simmen, Cornelia, Reichlin, Tobias, Chollet, Laurève, Lam, Anna, Wittmer, Severin, Rickli, Hans, Gall, Christian, Hametner, Greta, Intorp, Stephanie, Luescher, Daniel, Haegeli, Laurent, Berg, Jan Christopher, Ebrahimi, Ramin, Auricchio, Angelo, Crljenica, Carmela, Moccetti, Tizziano, Monti, Cristina, Pasotti, Elena, Petrova, Iveta, Rossi, Mariagrazia, Mach, François, Namdar, Mehdi, de Groot, Joris, Proost, Virginnio, Neefs, Joline, Linz, Dominik, van Stipdonk, Twan, den Uijl, Dennis, Alings, Marco, Schaap, Jeroen, Segers, Dolf, Wouters, Noemi, Bartels, Louis, Tieleman, Robert, Pisters, Ron, de Vries, Tim, Selig, Jaap, Kuijper, Aaf, Bot, Pieter, Keijzers, Mitran, Verdel, Gerardus, Tukkie, Raymond, van den Bos, Ewout, Kauer, Floris, Oemrawsingh, Rohit, Stevenhagen, Jeroen, van Es, Jan, Lip, Gregory, Gupta, Dhiraj, Kotalczyk, Agnieszka, Gunstone, Anthony, Brixey, Richard David, Gorog, Diana, Dinarvand, Danial, Gue, Ying, Kanji, Rahim, Memtsas, Vassilios, Senior, Roxy, Bioh, Gabriel, Wong, Yuk-Ki, Child, Nick, Piccini, Jonathan P, Caso, Valeria, Connolly, Stuart J, Fox, Keith A A, Oldgren, Jonas, Jones, W Schuyler, Gorog, Diana A, Durdil, Václav, Viethen, Thomas, Neumann, Christoph, Mundl, Hardi, and Patel, Manesh R

Published
2022
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5. Real-world performance and clinical outcome of comprehensive genomic profiling of gastrointestinal tumors: High-volume, single-center experience.

Author

Ricagno, Gianmarco, primary, Angerilli, Valentina, additional, Maddalena, Giulia, additional, De Toni, Chiara, additional, Gasparello, Jessica, additional, Barsotti, Giulia, additional, Mattiuzzo, Elena, additional, Ceccon, Carlotta, additional, Montagna, Aldo, additional, Sabbadin, Marianna, additional, Pittarello, Chiara, additional, Nappo, Floriana, additional, Cerantola, Riccardo, additional, Pante, Francesca, additional, Procaccio, Letizia, additional, Rizzato, Mario Domenico, additional, De Rosa, Antonio, additional, Fassan, Matteo, additional, Bergamo, Francesca, additional, and Lonardi, Sara, additional

Published
2024
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8. 2-Alkoxycarbonyl-3-arylamino-5-substituted thiophenes as a novel class of antimicrotubule agents: Design, synthesis, cell growth and tubulin polymerization inhibition

Author

Romagnoli, Romeo, Kimatrai Salvador, Maria, Schiaffino Ortega, Santiago, Baraldi, Pier Giovanni, Oliva, Paola, Baraldi, Stefania, Lopez-Cara, Luisa Carlota, Brancale, Andrea, Ferla, Salvatore, Hamel, Ernest, Balzarini, Jan, Liekens, Sandra, Mattiuzzo, Elena, Basso, Giuseppe, and Viola, Giampietro

Published
2018
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11. Risk of parenterally transmitted hepatitis following exposure to invasive procedures in Italy: SEIEVA surveillance 2000-2021

Author

Caminada, Susanna, primary, Mele, Annamaria, additional, Ferrigno, Luigina, additional, Alfonsi, Valeria, additional, Crateri, Simonetta, additional, Iantosca, Giuseppina, additional, Sabato, Marise, additional, Tosti, Maria Elena, additional, D’Angelo, Franca, additional, Zotti, Carla, additional, Marengo, Noemi, additional, Cornio, Alessandro Roberto, additional, Russotto, Antonino, additional, Scarvaglieri, Maria Elisabetta, additional, Gallone, Angela, additional, Zoia, Irene, additional, Torchio, Pierfederico, additional, Melcarne, Lucia, additional, Castagno, Paolo, additional, Bassetti, Saveria, additional, Dama, Erika, additional, Orlandi, Silvia, additional, Busso, Stefania, additional, Andreoletti, Michela, additional, Fontana, Manuela, additional, Rametta, Stefania, additional, Cranco, Rosita, additional, Bonacina, Alessandra, additional, Lioce, Duilio, additional, Ciprioti, Rosamary, additional, Cappello, Maria Teresa, additional, Palma, Anna Maria, additional, Musso, Claudia, additional, Bussolino, Paola, additional, Smaniotto, Alessandro, additional, Ruffier, Mario, additional, Verardo, Marina, additional, Cipriani, Alessandro, additional, Cereda, Danilo, additional, Senatore, Sabrina, additional, Donadini, Annalisa, additional, Nespoli, Carla, additional, Gennati, Giorgio, additional, Piro, Antonio, additional, Vezzosi, Luigi, additional, Conca, Matteo, additional, Romani, Michela, additional, Tortorella, Franco Paolo, additional, Merlini, Paola Elvira, additional, Di Caterina, Davide, additional, Faccini, Marino, additional, Lamberti, Anna, additional, Rossetti, Eva, additional, Brugnoli, Rita, additional, Mainardi, Giulia, additional, Vezzoli, Alessandra, additional, Caso, Daniela, additional, Testa, Milena, additional, Costa, Daniela, additional, Senegaglia, Paola, additional, Spagna, Annamaria, additional, Lodola, Silvia, additional, Riboli, Simona, additional, Giompapa, Enza, additional, Roveri, Luigi Guido, additional, Guardigli, Gabriele, additional, Scalvinoni, Vanna, additional, Lombarda, Elena, additional, Gasparri, Serena, additional, Spertini, Silvia, additional, Gamper, Sabine, additional, Moretto, Giacomo, additional, Kofler, Elisabeth, additional, Ploner, Barbara, additional, Runggatscher, Verena, additional, Molinaro, Silvia, additional, Zuccali, Maria Grazia, additional, Franchini, Silvia, additional, Russo, Francesca, additional, Zanella, Francesca, additional, Ballarin, Debora, additional, Fiorito, Nahuel, additional, Zallot, Chiara, additional, Cian, Serena, additional, Bonsembiante, Erminio, additional, Mattiuzzo, Elena, additional, Munarin, Ludovica, additional, Palazzi, Barbara, additional, Sulaj, Arda, additional, Boin, Federica, additional, Carraro, Daniele, additional, Codolo, Antonella, additional, Fragapane, Marilena, additional, Formaglio, Andrea, additional, Giacobbe, Donatella, additional, Fenzi, Federica, additional, Gottardello, Lorena, additional, Cannizzo, Elisabetta, additional, Ceccon, Giulia, additional, De Stefani, Emanuela, additional, Casagrande, Paola, additional, Zotto, Alessandra Dal, additional, Zotto, Rita Dal, additional, Carlotto, Antonio, additional, Zorzi, Gemma, additional, Ivanovska, Sandra, additional, Postiglione, Chiara, additional, Colucci, Laura, additional, Rocco, Giulio, additional, Stacul, Rossana, additional, Breda, Ariella, additional, Bortolossi, Marisa, additional, Iob, Andrea, additional, Micossi, Simonetta, additional, Feltrin, Oriana, additional, Caernelos, Giuseppina, additional, Mela, Marco, additional, Frumento, Virna, additional, Opisso, Anna, additional, Cuccu, Alessandro, additional, Carpi, Antonella, additional, Giuffra, Paola, additional, Torracca, Francesca, additional, Castiglioni, Laura, additional, Mattei, Giovanna, additional, Gualanduzzi, Claudio, additional, Massimiliani, Erika, additional, Rampini, Alessandra, additional, Paglioli, Silvia, additional, Bisaccia, Eufemia, additional, Roversi, Sandra, additional, Resi, Davide, additional, Prengka, Anna, additional, Califano, Annalisa, additional, Santoro, Viviana, additional, Biguzzi, Emilia, additional, Reali, Chiara, additional, Morri, Michela, additional, Senatore, Daniela, additional, Balocchini, Emanuela, additional, Pierozzi, Costanza, additional, Angio, Francesco, additional, Kundisova, Lucia, additional, Isola, Alda, additional, Cecconi, Rossella, additional, Berti, Cristiana, additional, Matarazzo, Francesca, additional, Zini, Paola, additional, Staderini, Chiara, additional, Cordella, Vincenzo, additional, Brugnoli, Sara, additional, Sacchelli, Francesco, additional, Lucchesi, Lara, additional, Luzzoli, Rosa, additional, Gandolfo, Silvia, additional, Cibeca, Piero, additional, Galletti, Nicoletta, additional, Aquino, Francesco, additional, Lari, Maria, additional, Poropat, Roberta, additional, Ferrini, Rita, additional, Barbieri, Alessandro, additional, Conti, Vito, additional, Canale, Alice, additional, Moretti, Katia, additional, Buccino, Aniello, additional, Bartoli, Ilaria, additional, Cioni, Silvia, additional, Gennari, Giulia, additional, Rapaccini, Fabiola, additional, Bekshiu, Lumturi, additional, Zacchini, Federica, additional, Romani, Davide, additional, Sansone, Monica, additional, Foresi, Simona, additional, Piattellini, Giovanni, additional, Pasquale, Anna, additional, Brancaleoni, Maria Grazia, additional, Santocchia, Franco, additional, Proietti, Maria Laura, additional, Fiacchini, Daniel, additional, Giamprini, Maria Sole, additional, Iacobellis, Mariangela, additional, Van Will, Jacqueline, additional, Vaccaro, Alfredo, additional, Sbarbati, Maria Margherita, additional, Amelio, Alessandra, additional, Cimini, Daniela, additional, Moroni, Vania, additional, Francoletti, Daniela, additional, Marcellini, Mirella, additional, Scaccia, Federica, additional, Branchesi, Elisabetta, additional, Saracino, Selena, additional, Mezzanotte, Catia, additional, Cimica, Susanna, additional, Vitale, Vita, additional, Laici, Franca, additional, Petrelli, Irene, additional, Airini, Barbara, additional, Passarini, Gabriella, additional, Ruffini, Lucia, additional, Lambertucci, Anna Maria, additional, Mogetta, Annarita, additional, Ciarrocchi, Giuseppe, additional, Pistolesi, Marina, additional, Fratello, Erika, additional, Picciotti, Francesca, additional, Contrisciani, Roberta, additional, Angelini, Claudio, additional, Ribiscini, Silvia, additional, Scognamiglio, Paola, additional, Vairo, Francesco, additional, De Santis, Claudia, additional, Miglietta, Antonio Salvatore, additional, Colosi, Alberto, additional, Loffredo, Maria Rosaria, additional, Esterini, Giorgio, additional, Pendenza, Alessio, additional, Nappi, Maria Rosaria, additional, Casagni, Luca, additional, Santucci, Luigi, additional, Montecchi, Margherita, additional, Mangiagli, Franca, additional, Aquilani, Silvia, additional, Di Luzio, Giuseppe, additional, Provvidenti, Luca, additional, Giambi, Cristina, additional, Di Giacomo, Manuela, additional, Giansanti, Enrico, additional, Mancini, Cristiana, additional, Turchi, Claudio, additional, Soldato, Graziella, additional, D'Eugenio, Felesina, additional, Albanesi, Ida, additional, Montanaro, Carmen, additional, Di Giorgio, Giovanni, additional, Prozzo, Alessandra, additional, Sabatini, Paola, additional, Simonelli, Mena, additional, Morrone, Gaetano, additional, Citarella, Annarita, additional, Fossi, Elena, additional, Alfieri, Rosa, additional, Scotto, Milena, additional, Caiazzo, Anna Luisa, additional, Liquori, Antonia, additional, Chironna, Maria, additional, Prato, Rosa, additional, Martinelli, Domenico, additional, Fortunato, Francesca, additional, Cappelli, Maria Giovanna, additional, Loconsole, Daniela, additional, Morea, Anna, additional, Del Matto, Giulia, additional, Maluccio, Maria Giuseppina, additional, Pedote, Pasquale, additional, Termite, Stefano, additional, Cambria, Roberta, additional, Caputi, Giovanni, additional, Cipriani, Rosati, additional, Desiante, Francesco, additional, Menolascina, Stefania, additional, Laforgia, Vera, additional, Squicciarini, Rosella, additional, Vitale, Viviana, additional, Matera, Anna Maria, additional, Pagone, Onofrio, additional, Avella, Grazia Maria, additional, Madaro, Antonino, additional, Angelillis, Raffaele, additional, Moffa, Giuseppina, additional, Nesta, Maria, additional, De Santis, Carlo, additional, Ferraro, Marisa, additional, Aprile, Valerio, additional, Antonazzo, Marcello, additional, Laugello, Giovanni, additional, Mignuoli, Anna Domenica, additional, Afflitto, Giuseppe, additional, Caroleo, Benedetto, additional, Scrivano, Francesca, additional, Maradei, Antonio, additional, Romeo, Rocco Cataldo, additional, Zucco, Rossella, additional, Coscarelli, Pierluigi, additional, Bisbano, Alessandro, additional, Monesanti, Maria, additional, De Giorgio, Vincenzo, additional, Giordano, Antonella, additional, Mammì, Pier Domenico, additional, Lazzarino, Elisa, additional, Surace, Vittoria, additional, Mangione, Rossana, additional, Meli, Valentina, additional, Cuccia, Mario, additional, Longhitano, Elena, additional, Delogu, Fiorenzo, additional, Fracasso, Donatella, additional, Marceddu, Maria Vittoria, additional, Flore, Loredana, additional, Eugenia Marras, Maria Valentina, additional, Serpi, Rita, additional, Campus, Marco, additional, and Raggio, Alessia, additional

Published
2023
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13. Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study

Author

Piccini, Jonathan P, primary, Caso, Valeria, additional, Connolly, Stuart J, additional, Fox, Keith A A, additional, Oldgren, Jonas, additional, Jones, W Schuyler, additional, Gorog, Diana A, additional, Durdil, Václav, additional, Viethen, Thomas, additional, Neumann, Christoph, additional, Mundl, Hardi, additional, Patel, Manesh R, additional, Auer, Johann, additional, Hubauer, Martin, additional, Pandzic, Sead, additional, Preishuber, Eva, additional, Primus-Grabscheit, Carina, additional, Reitgruber, Dietmar, additional, Schmalzer, Florian, additional, Adlbrecht, Christopher, additional, Schober, Andreas, additional, Hajos, Johannes, additional, Keil, Christoph, additional, Schratter, Alexandra, additional, Frick, Matthias, additional, Benda, Magdalena Anna, additional, Mächler, Maximilian, additional, Mutschlechner, Beatrix, additional, Saely, Christoph, additional, Sprenger, Lukas, additional, Lichtenauer, Michael, additional, Eber, Miriam, additional, Hoppe, Uta, additional, Kolbitsch, Tobias, additional, Jirak, Peter Michael, additional, Mirna, Moritz, additional, Schönbauer, Robert, additional, Bergler-Klein, Jutta, additional, Hengstenberg, Christian, additional, Stojkovic, Stefan, additional, Scherr, Daniel, additional, Manninger-Wünscher, Martin, additional, Rohrer, Ursula, additional, Stühlinger, Markus, additional, Schgoer, Wilfried, additional, Schwarzl, Jana, additional, Pürerfellner, Helmut, additional, Derndorfer, Michael, additional, Ebner, Christian, additional, Eder, Veronika, additional, Kollias, Georgios, additional, Sturmberger, Thomas, additional, Sieghartsleitner, Stefan, additional, Vijgen, Johan, additional, Koopman, Peter, additional, Dujardin, Karl, additional, Anné, Wim, additional, De Ceuninck, Michel, additional, Tavernier, Rene, additional, Duytschaever, Mattias, additional, Knecht, Sébastien, additional, Missault, Luc, additional, Vandekerckhove, Yves, additional, Rossenbacker, Tom, additional, Ector, Bavo, additional, Charlier, Filip, additional, Debruyne, Philippe, additional, Dewilde, Willem, additional, Janssens, Luc, additional, Roosen, John, additional, Vankelecom, Bart, additional, Heidbuchel, Hein, additional, Delesie, Michiel, additional, Vervoort, Gert, additional, Rombouts, Hans, additional, Vanassche, Thomas, additional, Engelen, Matthias, additional, Verhamme, Peter, additional, Willems, Rik, additional, Constance, Christian, additional, Pranno, Nicolas, additional, Cox, Jafna, additional, Bata, Iqbal, additional, Macle, Laurent, additional, Aguilar, Martin, additional, Tourigny, Julia Cadrin, additional, Dubuc, Marc, additional, Dyrda, Katia, additional, Guerra, Peter, additional, Khairy, Paul, additional, Mondésert, Blandine, additional, Rivard, Léna, additional, Roy, Denis, additional, Tadros, Rafik, additional, Talajic, Mario, additional, Thibault, Bernard, additional, Nault, Isabelle, additional, Blier, Louis, additional, Champagne, Jean, additional, Molin, Franck, additional, O'Hara, Gilles, additional, Philippon, François, additional, Plourde, Benoit, additional, Sarrazin, Jean-François, additional, Steinberg, Christian, additional, Coufal, Zdenek, additional, Balazsik, David, additional, Mikulica, Michal, additional, Zapeca, Jakub, additional, Cermak, Ondrej, additional, Drasnar, Tomas, additional, Falc, Matej, additional, Hornof, Josef, additional, Racz, Blazej, additional, Weissova, Danica, additional, Linkova, Hana, additional, Paskova, Eva, additional, Petr, Robert, additional, Sirakova, Andrea, additional, Kettner, Jiri, additional, Benak, Ales, additional, Holek, Martin, additional, Podpera, Ivo, additional, Podperova, Monika, additional, Vancura, Vlastimil, additional, Jandik, Tomas, additional, Smid, Jiri, additional, Dedek, Vratislav, additional, Banik, Jan, additional, Durdil, Vaclav, additional, Hnat, Tomas, additional, Lellouche, Nicolas, additional, Rouffiac, Ségolène, additional, Taldir, Guillaume, additional, Bridonneau, Valentin, additional, Couffon, Philippe, additional, Daudin, Magalie, additional, Hamon, Cécile, additional, Lacaze, Jonathan, additional, Quentin, Anne, additional, Thebault, Christophe, additional, Boiffard, Emmanuel, additional, Billon, Olivier, additional, Miette, Fabien, additional, Pouliquen, Hervé, additional, Turlotte, Guillaume, additional, Gorka, Hervé, additional, Albert, Franck, additional, Bayle, Sandrine, additional, Bensaid, Reda, additional, Dasoveanu, Madalina, additional, Demichili, Thibaud, additional, Dutoiu, Teodora, additional, Khalil, Cliff, additional, Loghin, Caterina, additional, Range, Grégoire, additional, Roussel, Laurent, additional, Socié, Pierre, additional, Thuaire, Christophe, additional, Extramiana, Fabrice, additional, Algalarrondo, Vincent, additional, Boughanmi, Haten, additional, El Mansour, Noreddine, additional, Mohammad, Usman, additional, Sellier, Romain, additional, Elbaz, Meyer, additional, Laperche, Clémence, additional, Maury, Philippe, additional, Kiss, Robert, additional, Borsanyi, Tunde, additional, Gingl, Zoltan, additional, Polgar, Balaza, additional, Benczur, Bela, additional, Bodor, Alexandra, additional, Hepp, Tamas, additional, Malati, Eva, additional, Nagy, Laszlo, additional, Erdei, Norbert, additional, Kapus, Jozsef, additional, Kapus, Katalin, additional, Toth, Brigitta, additional, Matoltsy, Andras, additional, Kiss, Tunde, additional, Merkely, Bela, additional, Herczeg, Szilvia, additional, Kiss, Orsolya, additional, Sallo, Zoltan, additional, Toth, Kalman, additional, Habon, Tamas, additional, Rabai, Miklos, additional, Totsimon, Kinga, additional, Zilahi, Zsolt, additional, Bencze, Gabriella, additional, Santa, Janos, additional, Aradi, Daniel, additional, Kelemen, Barbara, additional, Bolognese, Leonardo, additional, Nesti, Martina, additional, Notarstefano, Pasquale Giovanni, additional, D'Orazio, Simona, additional, Cosmi, Franco, additional, Becattini, Cecilia, additional, Agnelli, Giancarlo, additional, Broccatelli, Belinda, additional, Mosconi, Maria Giulia, additional, Paciaroni, Maurizio, additional, Urbini, Chiara, additional, Parato, Vito Maurizio, additional, Notaristefani, Camilla, additional, Scarano, Michele, additional, Ameri, Pietro, additional, Ghigliotti, Giorgio, additional, Guglielmi, Giulia, additional, Lotti, Roberta, additional, Merlo, Andrea Carlo, additional, Muiesan, Maria Lorenza, additional, Abondio, Andrea, additional, Berasi, Caterina, additional, Mattiuzzo, Elena, additional, Mutti, Claudio, additional, Salvetti, Massimo, additional, Pignatelli, Pasquale, additional, Menichelli, Danilo, additional, Pastori, Daniele, additional, Tamiya, Eiji, additional, Matsumoto, Takahiro, additional, Takabe, Tomosato, additional, Yamamoto, Shoichi, additional, Yamashita, Haruyo, additional, Higashiue, Shinichi, additional, Furuya, Onichi, additional, Hiramatsu, Norihiko, additional, Kasuga, Kensuke, additional, Kojima, Saburo, additional, Komooka, Masatoshi, additional, Kuroyanagi, Satoshi, additional, Matsuura, Makoto, additional, Takemoto, Tetsushi, additional, Yamamoto, Shuji, additional, Saito, Katusmi, additional, Abe, Takuro, additional, Ishida, Issei, additional, Iwanami, Yuji, additional, Kataoka, Shohei, additional, Moriyama, Tetsu, additional, Murohashi, Akira, additional, Sasaki, Akihito, additional, Nakamura, Yuichiro, additional, Ueno, Tetsuya, additional, Shimane, Akira, additional, Hamana, Tomoyo, additional, Ichibori, Hirotoshi, additional, Inoue, Tomohiro, additional, Itoh, Mitsuaki, additional, Iwane, Seigo, additional, Kawai, Hiroya, additional, Kokawa, Tatsuya, additional, Masumoto, Akiko, additional, Matsuo, Koki, additional, Miyata, Taishi, additional, Nakano, Shinsuke, additional, Oishi, Shogo, additional, Onishi, Tetsuari, additional, Sawada, Takahiro, additional, Saito, Takayuki, additional, Shoda, Mitsuhiko, additional, Takahashi, Nobuyuki, additional, Takaya, Tomofumi, additional, Taniguchi, Yasuyo, additional, Tsukamoto, Shota, additional, Tsukishiro, Yasue, additional, Tsukiyama, Yoshiro, additional, Tsunamoto, Hiroshi, additional, Uzu, Kenzo, additional, Yamamoto, Hiroyuki, additional, Yamamoto, Tetsuya, additional, Yokoi, Kiminobu, additional, Yoshida, Chiaki, additional, Watanabe, Nobuhiro, additional, Betsuyaku, Tetsuo, additional, Adachi, Kumiko, additional, Awane, Kouichi, additional, Goto, Daisuke, additional, Sakakibara, Mamoru, additional, Watanabe, Masashi, additional, Ueno, Hideki, additional, Hiroe, Yoshitaka, additional, Matsuo, Koshi, additional, Ayata, Kenji, additional, Fukuda, Ko, additional, Hata, Yoshiki, additional, Hashimoto, Katsushi, additional, Matsumi, Hiroaki, additional, Nikaido, Akira, additional, Okamoto, Shuichi, additional, Sime, Iveta, additional, Stirna, Valters, additional, Reinholde, Ilze, additional, Hansone, Silvija, additional, Kozlovska, Anita, additional, Romanova, Janina, additional, Klincare, Dace, additional, Pontaga, Natalja, additional, Dirmans, Igors, additional, Kalnins, Artis, additional, Upite, Dana, additional, Gersamija, Arcils, additional, Teleznikovs, Arturs, additional, Rozkova, Nadezda, additional, Safro, Jelena, additional, Anguera Camós, Ignasi, additional, Domenico Dallaglio, Paolo, additional, Salguero Bodes, Rafael, additional, Arnbas, Fernando, additional, Borrego, Luis, additional, Marco, Alvaro, additional, Jimenez, Javier Ramos, additional, Gómez-Doblas, Juan José, additional, Pérez Cabeza, Alejandro, additional, Ferreira Gonzålez, Ignacio, additional, Limeres Freire, Javier, additional, Lopez Grau, Merce, additional, Viñolas Prat, Xavier, additional, Moreno Weidmann, Zoraida, additional, Guerra Ramos, Jose Maria, additional, Alonso Martin, Maria Concepcion, additional, Campos Garcia, Bieito, additional, Mogro Carranza, Javier Mauricio, additional, Mendez Zurita, Francisco Javier, additional, Rodriguez Font, Enrique, additional, Gonzales Matos, Carlos Eduardo, additional, García Hernando, Víctor, additional, Lindholm, Carl-Johan, additional, Thulin, Jörgen, additional, Wallén, Håkan, additional, Hagwall, Kristina, additional, Eliasson, Ken, additional, Lundvall, Martin, additional, Olsson, Jens, additional, Kjellman, Björn, additional, Lind, Markus, additional, Johansson, Lars, additional, Svedberg, Niclas, additional, Berglund, Stefan, additional, Söderberg, Julia, additional, Zedigh, Christer, additional, Mooe, Thomas, additional, Axelsson, Mattias, additional, Binsell, Emil, additional, Huber, Daniel, additional, Müller, Christian, additional, Danier, Isabelle, additional, Kühne, Michael, additional, Okamura, Bernhard, additional, Schoepfer, Hadrien, additional, Simmen, Cornelia, additional, Reichlin, Tobias, additional, Chollet, Laurève, additional, Lam, Anna, additional, Wittmer, Severin, additional, Rickli, Hans, additional, Gall, Christian, additional, Hametner, Greta, additional, Intorp, Stephanie, additional, Luescher, Daniel, additional, Haegeli, Laurent, additional, Berg, Jan Christopher, additional, Ebrahimi, Ramin, additional, Auricchio, Angelo, additional, Crljenica, Carmela, additional, Moccetti, Tizziano, additional, Monti, Cristina, additional, Pasotti, Elena, additional, Petrova, Iveta, additional, Rossi, Mariagrazia, additional, Mach, François, additional, Namdar, Mehdi, additional, de Groot, Joris, additional, Proost, Virginnio, additional, Neefs, Joline, additional, Linz, Dominik, additional, van Stipdonk, Twan, additional, den Uijl, Dennis, additional, Alings, Marco, additional, Schaap, Jeroen, additional, Segers, Dolf, additional, Wouters, Noemi, additional, Bartels, Louis, additional, Tieleman, Robert, additional, Pisters, Ron, additional, de Vries, Tim, additional, Selig, Jaap, additional, Kuijper, Aaf, additional, Bot, Pieter, additional, Keijzers, Mitran, additional, Verdel, Gerardus, additional, Tukkie, Raymond, additional, van den Bos, Ewout, additional, Kauer, Floris, additional, Oemrawsingh, Rohit, additional, Stevenhagen, Jeroen, additional, van Es, Jan, additional, Lip, Gregory, additional, Gupta, Dhiraj, additional, Kotalczyk, Agnieszka, additional, Gunstone, Anthony, additional, Brixey, Richard David, additional, Gorog, Diana, additional, Dinarvand, Danial, additional, Gue, Ying, additional, Kanji, Rahim, additional, Memtsas, Vassilios, additional, Senior, Roxy, additional, Bioh, Gabriel, additional, Wong, Yuk-Ki, additional, and Child, Nick, additional

Published
2022
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19. Pharmacological studies of novel antitumoral compounds

Author

Mattiuzzo, Elena

Subjects
MED/06 Oncologia medica, glucocorticoids, Settore MED/06 - Oncologia Medica, leukemia, cell cycle, glucocorticoids, cell cycle, leukemia
Abstract

Over the years biomedical research was focused on the development of new anticancer agents able to selectively target cancer cells at low concentration efficacy. Based on the idea that oncogenes and tumour suppressor genes are a critical force in the malignant transformation of cells, research efforts have focused on developing drugs that directly target these genes. In the first study we focused on B-cell acute lymphoblastic leukaemia (B-ALL), that is one of the most common paediatric malignant disorders characterized by an accumulation of B-cell blasts reminiscent of normal stages of differentiation and by infiltration of various extramedullary sites. Excessive cell proliferation induced by aberrant entry into the cell cycle is considered an hallmark of cancer. Recent findings have revealed that CDK4/6 and its regulatory subunit cyclin D1 are potentially oncogenes and are overexpressed in a diverse set of human cancers, including B-cell acute lymphoblastic leukemia (B-ALL). Moreover, CDK6 is essential for MLL-rearranged leukemias. These findings suggest that CDK4/6 may be effective targets for therapeutic intervention. To test this possibility, we have inhibited CDK4 and CDK6 in four cell lines of B-ALL, characterized by different genetic rearrangements, using Ribociclib, an orally bioavailable, small molecule inhibitor of both CDK4 and CDK6. At low concentration, Ribociclib potently inhibit CDK4/6 without induction of apoptosis; therefore, standard treatment for newly diagnosed childhood B-ALL patients includes glucocorticoids (GC) treatment, but the molecular basis of GC sensitivity and resistance remains largely unknown; for this reason we have tested if Ribociclib in combination with Dexamethasone, a glucocorticoid that is currently used as antitumour agent in the treatment of leukemia, may lead to synergistic killing of leukemia cells. B-ALL patients that respond poorly to glucocorticoid therapy when diagnosed are usually predicted to undergo relapse. Therefore, understanding the biological mechanisms underlying this poor responsiveness is crucial for the development of more effective therapies.

Published
2018

20. The Viability and Anti-Inflammatory Effects of Hyaluronic Acid-Chitlac-Tracimolone Acetonide- β-Cyclodextrin Complex on Human Chondrocytes

Author

Tarricone, Elena, Elia, Rossella, Mattiuzzo, Elena, Faggian, Alessia, Pozzuoli, Assunta, Ruggieri, Pietro, and Brun, Paola

Abstract

Objective To compare the effects of the complex triamcinolone acetonide-hydroxypropyl-β-cyclodextrin (TA-CD) on in vitroinflamed primary human articular chondrocytes in the presence or absence of the mixture hyaluronic acid-Chitlac, a lactose-modified chitosan (HA-CTL).Design Changes in cell viability and pro-inflammatory cytokines gene expression were analyzed in human chondrocytes using an in vitromodel of macrophage-mediated inflammation. Human monocytes U937 were differentiated to macrophages by phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharides (LPS). The anti-inflammatory effects of the complex TA-CD and HA-CTL mixture were assessed on chondrocytes exposed for 24 hours to U937 conditioned medium (CM), by quantitative polymerase chain reaction analysis.Results The TA-CD viability was enhanced by the presence of the HA-CTL mixture in chondrocyte cultures. The exposure of cells to CM significantly increased interleukin-1β and interleukin-6 gene expression, and when the complex TA-CD was added to the inflamed cells, gene transcription of cytokines was restored to near baseline values, both in the presence or in the absence of HA-CTL mixture.Conclusion The addition of HA-CTL mixture significantly attenuated cytotoxicity induced by TA and preserved the anti-inflammatory effects, thus confirming the chondroprotective role of the HA-CTL mixture.

Published
2021
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21. Design, Synthesis, and Biological Evaluation of 6-Substituted Thieno[3,2-d]pyrimidine Analogues as Dual Epidermal Growth Factor Receptor Kinase and Microtubule Inhibitors

Author

Romagnoli, Romeo, primary, Prencipe, Filippo, additional, Oliva, Paola, additional, Baraldi, Stefania, additional, Baraldi, Pier Giovanni, additional, Schiaffino Ortega, Santiago, additional, Chayah, Mariem, additional, Kimatrai Salvador, Maria, additional, Lopez-Cara, Luisa Carlota, additional, Brancale, Andrea, additional, Ferla, Salvatore, additional, Hamel, Ernest, additional, Ronca, Roberto, additional, Bortolozzi, Roberta, additional, Mariotto, Elena, additional, Mattiuzzo, Elena, additional, and Viola, Giampietro, additional

Published
2019
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22. Lead Optimization-Hit Expansion of New Asymmetrical Pyridinium/Quinolinium Compounds as Choline Kinase α1 Inhibitors

Author

Rubbini, Gianluca, primary, Buades-Martín, Ana Begoña, additional, Kimatrai-Salvador, María, additional, Entrena, Antonio, additional, Gallo-Mezo, Miguel Ángel, additional, Ríos-Marco, Pablo, additional, Marco, Carmen, additional, Mattiuzzo, Elena, additional, Bortolozzi, Roberta, additional, Mariotto, Elena, additional, Greco, Francesco Antonio, additional, Macchiarulo, Antonio, additional, Carrasco-Jiménez, María Paz, additional, Viola, Giampietro, additional, and López-Cara, Luisa Carlota, additional

Published
2018
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26. Multicomponent Approach to Bioactive Peptide-Ecdysteroid Conjugates: Creating Diversity at C6 by Means of the Ugi Reaction.

Author

Lesma, Giordano, Luraghi, Andrea, Rainoldi, Giulia, Mattiuzzo, Elena, Bortolozzi, Roberta, Viola, Giampietro, and Silvani, Alessandra

Subjects
CONJUGATED polymers, ECDYSTEROIDS, PEPTIDES, ECDYSONE, ORGANIC semiconductors
Abstract

An efficient multicomponent protocol has been developed to access two different kinds of peptide-ecdysteroid conjugates. The approach exploits the reactivity of the 6-keto-7-ene group of 20-OH-ecdysone, allowing the unprecedented preparation of 6-amino and 6-isocyanide derivatives. The ecdysteroid derivatives were further employed in the Ugi reaction, together with formaldehyde and various structurally diverse carboxylic acids, isocyanides and amines, to afford a small family of potential multidrug-resistance modulators. [ABSTRACT FROM AUTHOR]

Published
2016
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27. Evaluation of the β-Caryophyllene effects alone or in combination with Ascorbic Acid and d-Glucosamine on inflamed Human Chondrocytes.

Author

Belluzzi, Elisa, Mattiuzzo, Elena, Faggian, Alessia, Venerando, Rina, Benetti, Andrea, Ruggieri, Pietro, and Brun, Paola

Subjects
*CARTILAGE cells, *VITAMIN C, *EXTRACELLULAR matrix, *ARTICULAR cartilage, *INFLAMMATORY mediators, *STAINS & staining (Microscopy), *FIBRONECTINS, *MONOCYTES
Abstract

Background: Osteoarthritis (OA) is a disabling disease affecting all joint tissues and particularly articular cartilage. Moreover, inflammatory process and mediators plays an important role in the initiation and progression of OA determining cartilage extracellular matrix degradation. Aim: The aim of this study is to evaluate the effects of β-caryophyllene (BCP), a plantderived sesquiterpene with anti-inflammatory and antioxidant properties, alone or in combination with ascorbic acid (AA) and d-glucosamine (GlcN) on human primary chondrocytes inflamed with macrophage-derived conditioned medium (CM). Materials and Methods: Cartilage biopsies were obtained from OA patients and controls. Histological staining and immunohistochemistry for inflammatory markers were performed to characterize the tissues. Chondrocytes cell viability, gene expression of pro-inflammatory mediators, metalloproteinases (MMPs), collagen type II and aggrecan levels were analyzed in primary human chondrocytes isolated from OA patients and exposed to the CM of activated U937 monocytes and subsequently treated with BCP alone or in combination with AA and GlcN. Results: Histology and immunohistochemistry analysis pointed out cartilage degeneration, fragmentation and fissuring in OA patients, associated with the presence of positivity to inflammatory molecules compared to controls. The macrophage-derived CM induced a decrease of chondrocyte viability and a significantly increase of inflammatory molecules and MMPs expression. When BCP was added to the inflamed cells, alone or in combination with AA and GlcN, there was an increase of cell viability, a decrease of gene expression of interleukin-1 beta, NF-κB1 and MMP-13 and an increase of ECM matrix molecules (aggrecan and type II collagen). Conclusions: Low-doses of BCP are effective in counteracting the inflammatory effects determined by macrophage-derived CM stimulation on chondrocytes. Moreover, the combined used of BCP, AA and GlcN seems to have synergistic effects in protecting chondrocytes. [ABSTRACT FROM AUTHOR]

Published
2022

28. Autophagy in chronic obstructive pulmonary disease: a modelling study.

Author

Schinello, Giorgia, Mattiuzzo, Elena, Leonardi, Andrea, Di Stefano, Antonino, and Brun, Paola

Subjects
*CHRONIC obstructive pulmonary disease, *AUTOPHAGY
Abstract

The article discuses the role of autophagy in COPD using bronchial epithelial cells and primary bronchial fibroblast cultures treated with the inflammatory media of activated U937 monocytes and analyzed by qPCR and western blotting for the expression of the autophagy markers. LC3B expression was also increased in bronchial biopsies of severe/very severe COPD compared to mild to moderate diseased patients, and in comparison with control non-smokers.

Published
2021

29. Modulation of the LC3B and p62 expression in conjunctival fibroblasts by pro-inflammatory macrophages.

Author

Mattiuzzo, Elena, Tarricone, Elena, Leonardi, Andrea, Di Stefano, Antonino, and Brun, Paola

Subjects
*FIBROBLASTS, *AUTOPHAGY, *HOMEOSTASIS
Abstract

Autophagy is a key regulatory process involved in many biological aspects, including cell survival, tissue regeneration and homeostasis. Recent studies demonstrated that de-regulated autophagy is implicated in some inflammatory diseases. Previous data obtained in our laboratory demonstrated that some autophagic markers such as LC3B, cathpesin D, Beclin-1 are overexpressed in a severe inflammatory disease such as vernal keratoconjunctivitis (VKC). In the present study VKC conjunctival cell cultures were exposed to the inflammatory media of activated U937 monocytes to explore the role of inflammatory factors in the induction of autophagy. Macrophage differentiation of U937 was induced by LPS and PMA and then incubated with fresh DMEM and 10%FBS to produce the conditioned medium. qPCR analysis of the activated cells revealed that IL1beta, TNFalfa were overexpressed. Primary conjunctival cell cultures were then treated with the inflammatory medium conditioned by activated U937and analysed for expression of some autophagic markers at 4, 10 and 24 hours after exposure. qPCR results demonstrated that LC3B, Beclin-1, LAMP1 and p62 increased from 4 to 24 hours. Western blotting analysis revealed cleavage and lipidation of LC3B quantified as an increased LC3BII/LC3BI ratio. In conclusion, our data demonstrated that the environment created by inflammatory macrophages enahances autophagy in VKC conjunctival fibroblasts. [ABSTRACT FROM AUTHOR]

Published
2018

30. Design, synthesis and biological evaluation of 3-substituted-2-oxindole hybrid derivatives as novel anticancer agents

Author

Paola Oliva, Stefania Baraldi, Giuseppe Basso, Romeo Romagnoli, Pier Giovanni Baraldi, Elena Mattiuzzo, Roberta Bortolozzi, Maria Kimatrai Salvador, Luisa Carlota Lopez-Cara, Giampietro Viola, Filippo Prencipe, Romagnoli, Romeo, Baraldi, Pier Giovanni, Prencipe, Filippo, Oliva, Paola, Baraldi, Stefania, Salvador, Maria Kimatrai, Lopez Cara, Luisa Carlota, Bortolozzi, Roberta, Mattiuzzo, Elena, Basso, Giuseppe, and Viola, Giampietro

Subjects
0301 basic medicine, Indoles, Apoptosis, Drug Screening Assays, 2-Oxindole derivatives, In&nbsp, chemistry.chemical_compound, 0302 clinical medicine, GSH depletion, In vitro antiproliferative activity, Michael acceptor, α-bromoacryloyl, Antineoplastic Agents, Cell Line, Tumor, Cell Proliferation, Drug Screening Assays, Antitumor, Glutathione, Humans, Membrane Potential, Mitochondrial, Neoplasms, Reactive Oxygen Species, Structure-Activity Relationship, Drug Design, Pharmacology, Drug Discovery3003 Pharmaceutical Science, Organic Chemistry, In vitro antiproliferative activity, α-bromoacryloyl, Drug Discovery, 2-Oxindole derivative, chemistry.chemical_classification, Tumor, General Medicine, Mitochondrial, Biochemistry, 030220 oncology & carcinogenesis, medicine.symptom, Pharmacophore, Intracellular, Stereochemistry, vitro antiproliferative activity, Membrane Potential, Cell Line, NO, 03 medical and health sciences, medicine, IC50, Reactive oxygen species, Inundefined vitro antiproliferative activity, Antitumor, In vitro, Oxindoles, 030104 developmental biology, Mechanism of action, chemistry, Cell culture
Abstract

The 2-oxindole nucleus is the central core to develop new anticancer agents and its substitution at the 3-position can effect antitumor activity. Utilizing a pharmacophore hybridization approach, a novel series of antiproliferative agents was obtained by the modification of the structure of 3-substituted-2-oxindole pharmacophore by the attachment of the α-bromoacryloyl moiety, acting as a Michael acceptor, at the 5-position of 2-oxindole framework. The impact of the substituent at the 3-position of 2-oxindole core on the potency and selectivity against a panel of seven different cancer cell lines was examined. We found that these hybrid molecules displayed potent antiproliferative activity against a panel of four cancer cell lines, with one-to double digit nanomolar 50% inhibitory concentrations (IC50). A distinctive selective antiproliferative activity was obtained towards CCRF-CEM and RS4; 11 leukemic cell lines. In order to study the possible mechanism of action, we observed that the two most active compounds namely 3(E) and 6(Z) strongly induce apoptosis that follow the mitochondrial pathway. Interestingly a decrease of intracellular reduced glutathione content (GSH) and reactive oxygen species (ROS) production was detected in treated cells compared with controls suggesting that these effects may be involved in their mechanism of action.

Published
2017

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