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Your search keyword '"Abbruzzese, C."' showing total 10 results
Start Over Author "Abbruzzese, C." Publisher biomed central
10 results on '"Abbruzzese, C."'

1. Endothelial damage in septic shock patients as evidenced by circulating syndecan-1, sphingosine-1-phosphate and soluble VE-cadherin: a substudy of ALBIOS

Author

Piotti, A., Novelli, D., Meessen, J. M. T. A., Ferlicca, D., Coppolecchia, S., Marino, A., Salati, G., Savioli, M., Grasselli, G., Bellani, G., Pesenti, A., Masson, S., Caironi, P., Gattinoni, L., Gobbi, M., Fracasso, C., Latini, R., Bruzzone, P., Pagan, F., Russo, R., Confalonieri, A., Abbruzzese, C., Vergnano, B., Faenza, S., Siniscalchi, A., Pierucci, E., Noto, A., Pezzi, A., Spanu, P., Parrini, V., Oggioni, R., Pasetti, G. S., Casadio, M. C., Buontempo, R., Carrer, S., Piccoli, F., Rizzi, T., Caricato, A., La Sala, M., Antonaci, A., Fassini, P., Paganini, S., Porta, V., Moise, G., Marell, S., Furia, M., Urbano, M. C., Carobbi, R., Poleni, S., Kandil, H., Ballotta, A., Bettini, F., Sanseverino, M., Gatta, A., Cecchini, F., Guatteri, L., Ciceri, G., Raimondi, F., Colombo, R., Ferraris, S., Borelli, M., Bellato, V., Cancellieri, F., Senni, S., Bertocchi, E., Ferri, P., Moioli, G., Fedele, A., Molin, A., Salsi, P., Brunori, E., Elisei, D., Maggio, G., Nicola, F. G., Cavana, M., Morelli, G., Guarino, A., Isetta, M., Tulli, G., Mangani, V., Rossi, N., Ferrari, M., Bona, F., Vay, M., Bartoli, T., Gallo, M., Vettoretto, K., Morte, M. D., Boselli, E., Puscio, D., Bovo, M., Galzerano, A., Carli, M., Zagara, G., Piotti, A, Novelli, D, Meessen, J, Ferlicca, D, Coppolecchia, S, Marino, A, Salati, G, Savioli, M, Grasselli, G, Bellani, G, Pesenti, A, Masson, S, Caironi, P, Gattinoni, L, Gobbi, M, Fracasso, C, and Latini, R

Subjects
Male, Letter, medicine.medical_treatment, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Gastroenterology, 0302 clinical medicine, VE-cadherin, Sphingosine, Septic shock, 80 and over, Medicine, Endothelial dysfunction, Phosphorylation, Aged, 80 and over, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Shock, Biomarker, Glycocalyx, Sphingosine-1-phosphate, Syndecan-1, Aged, Antigens, CD, Biomarkers, Cadherins, Endothelium, Female, Humans, Italy, Lysophospholipids, Middle Aged, Retrospective Studies, Shock, Septic, Extravasation, 3. Good health, CD, Endothelial stem cell, medicine.medical_specialty, Sepsis, 03 medical and health sciences, Internal medicine, Albumins, Settore MED/41 - ANESTESIOLOGIA, Renal replacement therapy, Antigens, business.industry, Septic, Research, Albumin, 030208 emergency & critical care medicine, lcsh:RC86-88.9, medicine.disease, business
Abstract

Background Septic shock is characterized by breakdown of the endothelial glycocalyx and endothelial damage, contributing to fluid extravasation, organ failure and death. Albumin has shown benefit in septic shock patients. Our aims were: (1) to identify the relations between circulating levels of syndecan-1 (SYN-1), sphingosine-1-phosphate (S1P) (endothelial glycocalyx), and VE-cadherin (endothelial cell junctions), severity of the disease, and survival; (2) to evaluate the effects of albumin supplementation on endothelial dysfunction in patients with septic shock. Methods This was a retrospective analysis of a multicenter randomized clinical trial on albumin replacement in severe sepsis or septic shock (the Albumin Italian Outcome Sepsis Trial, ALBIOS). Concentrations of SYN-1, S1P, soluble VE-cadherin and other biomarkers were measured on days 1, 2 and 7 in 375 patients with septic shock surviving up to 7 days after randomization. Results Plasma concentrations of SYN-1 and VE-cadherin rose significantly over 7 days. SYN-1 and VE-cadherin were elevated in patients with organ failure, and S1P levels were lower. SYN-1 and VE-cadherin were independently associated with renal replacement therapy requirement during ICU stay, but only SYN-1 predicted its new occurrence. Both SYN-1 and S1P, but not VE-cadherin, predicted incident coagulation failure. Only SYN-1 independently predicted 90-day mortality. Albumin significantly reduced VE-cadherin, by 9.5% (p = 0.003) at all three time points. Conclusion Circulating components of the endothelial glycocalyx and of the endothelial cell junctions provide insights into severity and progression of septic shock, with special focus on incident coagulation and renal failure. Albumin supplementation lowered circulating VE-cadherin consistently over time. Clinical Trial Registration: ALBIOS ClinicalTrials.gov number NCT00707122.

Published
2021

2. Pressure support ventilation + sigh in acute hypoxemic respiratory failure patients: study protocol for a pilot randomized controlled trial, the PROTECTION trial

Author

Mauri, T, Foti, G, Fornari, C, Constantin, J, Guerin, C, Pelosi, P, Ranieri, M, Conti, S, Tubiolo, D, Rondelli, E, Lovisari, F, Fossali, T, Spadaro, S, Grieco, D, Navalesi, P, Calamai, I, Becher, T, Roca, O, Wang, Y, Knafelj, R, Cortegiani, A, Mancebo, J, Brochard, L, Pesenti, A, Grasselli, G, Spinelli, E, Abbruzzese, C, Rona, R, Bronco, A, Villa, S, Gianni, S, Papoff, A, Pinciroli, R, Colombo, R, Sproccati, C, Mandelli, P, Villa, F, Patroniti, N, Brunetti, I, Ball, L, Volta, C, Lazzeri, M, Maragoni, E, Eleuteri, D, Bello, G, Dell'Anna, A, Garofalo, E, Bruni, A, Biamonte, E, D'Andrea, R, Querci, L, Pierucci, E, Spina, R, Mori, I, Tomeo, F, Mercat, A, Beloncle, F, Jochmans, S, Mazerand, S, Baboi, L, Yonis, H, Jabaudon, M, Godet, T, Jovaisa, T, Barnes, T, Tariq, U, Weiler, N, Schädler, D, Frerichs, I, García-de-Acilu, M, Vidal, A, Rosas, E, Calvo, C, Zhou, J, Karagiannis, S, Zisopoulou, V, Staikos, I, Noc, M, Fister, M, Radsel, P, Gregoretti, C, Sabella, I, Raineri, S, Mauri, Tommaso, Foti, Giuseppe, Fornari, Carla, Constantin, Jean-Michel, Guerin, Claude, Pelosi, Paolo, Ranieri, Marco, Conti, Sara, Tubiolo, Daniela, RONDELLI, EGLE ROSALIA, Lovisari, Federica, Fossali, Tommaso, Spadaro, Savino, Grieco, Domenico Luca, Navalesi, Paolo, Calamai, Italo, Becher, Tobias, Roca, Oriol, Wang, Yu-Mei, Knafelj, Rihard, Cortegiani, Andrea, Mancebo, Jordi, Brochard, Laurent, Pesenti, Antonio, Volta, CA, dell'Anna, A, Calvo, CP, Zhou, JX, Raineri, SM, Mauri, T, Foti, G, Fornari, C, Constantin, J, Guerin, C, Pelosi, P, Ranieri, M, Conti, S, Tubiolo, D, Rondelli, E, Lovisari, F, Fossali, T, Spadaro, S, Grieco, D, Navalesi, P, Calamai, I, Becher, T, Roca, O, Wang, Y, Knafelj, R, Cortegiani, A, Mancebo, J, Brochard, L, Pesenti, A, Grasselli, G, Spinelli, E, Abbruzzese, C, Rona, R, Bronco, A, Villa, S, Gianni, S, Papoff, A, Pinciroli, R, Colombo, R, Sproccati, C, Mandelli, P, Villa, F, Patroniti, N, Brunetti, I, Ball, L, Volta, C, Lazzeri, M, Maragoni, E, Eleuteri, D, Bello, G, Dell'Anna, A, Garofalo, E, Bruni, A, Biamonte, E, D'Andrea, R, Querci, L, Pierucci, E, Spina, R, Mori, I, Tomeo, F, Mercat, A, Beloncle, F, Jochmans, S, Mazerand, S, Baboi, L, Yonis, H, Jabaudon, M, Godet, T, Jovaisa, T, Barnes, T, Tariq, U, Weiler, N, Schädler, D, Frerichs, I, García-de-Acilu, M, Vidal, A, Rosas, E, Calvo, C, Zhou, J, Karagiannis, S, Zisopoulou, V, Staikos, I, Noc, M, Fister, M, Radsel, P, Gregoretti, C, Sabella, I, Raineri, S, Mauri, Tommaso, Foti, Giuseppe, Fornari, Carla, Constantin, Jean-Michel, Guerin, Claude, Pelosi, Paolo, Ranieri, Marco, Conti, Sara, Tubiolo, Daniela, RONDELLI, EGLE ROSALIA, Lovisari, Federica, Fossali, Tommaso, Spadaro, Savino, Grieco, Domenico Luca, Navalesi, Paolo, Calamai, Italo, Becher, Tobias, Roca, Oriol, Wang, Yu-Mei, Knafelj, Rihard, Cortegiani, Andrea, Mancebo, Jordi, Brochard, Laurent, Pesenti, Antonio, Volta, CA, dell'Anna, A, Calvo, CP, Zhou, JX, and Raineri, SM

Abstract

BACKGROUND: Adding cyclic short sustained inflations (sigh) to assisted ventilation yields optimizes lung recruitment, decreases heterogeneity and reduces inspiratory effort in patients with acute hypoxemic respiratory failure (AHRF). These findings suggest that adding sigh to pressure support ventilation (PSV) might decrease the risk of lung injury, shorten weaning and improve clinical outcomes. Thus, we conceived a pilot trial to test the feasibility of adding sigh to PSV (the PROTECTION study). METHODS: PROTECTION is an international randomized controlled trial that will be conducted in 23 intensive care units (ICUs). Patients with AHRF who have been intubated from 24 h to 7 days and undergoing PSV from 4 to 24 h will be enrolled. All patients will first undergo a 30-min sigh test by adding sigh to clinical PSV for 30 min to identify early oxygenation responders. Then, patients will be randomized to PSV or PSV + sigh until extubation, ICU discharge, death or day 28. Sigh will be delivered as a 3-s pressure control breath delivered once per minute at 30 cmH2O. Standardized protocols will guide ventilation settings, switch back to controlled ventilation, use of rescue treatments, performance of spontaneous breathing trial, extubation and reintubation. The primary endpoint of the study will be to verify the feasibility of PSV + sigh evaluated through reduction of failure to remain on assisted ventilation during the first 28 days in the PSV + sigh group versus standard PSV (15 vs. 22%). Failure will be defined by switch back to controlled ventilation for more than 24 h or use of rescue treatments or reintubation within 48 h from elective extubation. Setting the power to 80% and first-risk order to 5%, the computed size of the trial is 129 patients per arm. DISCUSSION: PROTECTION is a pilot randomized controlled trial testing the feasibility of adding sigh to PSV. If positive, it will provide physicians with an effective addition to standard PSV for lung protection, a

Published
2018

3. 37th International Symposium on Intensive Care and Emergency Medicine (part 1 of 3)

Author

Karavana, V., Smith, I., Kanellis, G., Sigala, I., Kinsella, T., Zakynthinos, S., Liu, L., Chen, J., Zhang, X., Liu, A., Guo, F., Liu, S., Yang, Y., Qiu, H., Grimaldi, D. G., Kaya, E., Acicbe, O., Kayaalp, I., Asar, S., Dogan, M., Eren, G., Hergunsel, O., Pavelescu, D., Grintescu, I., Mirea, L., Guanziroli, M., Gotti, M., Marino, A., Cressoni, M., Vergani, G., Chiurazzi, C., Chiumello, D., Gattinoni, L., Spano, S., Massaro, F., Moustakas, A., Johansson, S., Larsson, A., Perchiazzi, G., Zhang, X. W., Guo, F. M., Chen, J. X., Xue, M., Qiu, H. B., Yang, L., Fister, M., Knafelj, R., Suzer, M. A., Kavlak, M. E., Atalan, H. K., Gucyetmez, B., Cakar, N., Weller, D., Grootendorst, A. F., Dijkstra, A., Kuijper, T. M., Cleffken, B. I., Regli, A., De Keulenaer, B., Van Heerden, P., Hadfield, D., Hopkins, P. A., Penhaligon, B., Reid, F., Hart, N., Rafferty, G. F., Grasselli, G., Mauri, T., Lazzeri, M., Carlesso, E., Cambiaghi, B., Eronia, N., Maffezzini, E., Bronco, A., Abbruzzese, C., Rossi, N., Foti, G., Bellani, G., Pesenti, A., Bassi, G. Li, Panigada, M., Ranzani, O., Kolobow, T., Zanella, A., Berra, L., Parrini, V., Kandil, H., Salati, G., Livigni, S., Amatu, A., Girardis, M., Barbagallo, M., Moise, G., Mercurio, G., Costa, A., Vezzani, A., Lindau, S., Babel, J., Cavana, M., Torres, A., Ranzani, O. T., Umbrello, M., Taverna, M., Formenti, P., Mistraletti, G., Vetrone, F., Baisi, A., Garnero, A. G., Novotni, D. N., Arnal, J. A., Urner, M., Fan, E., Dres, M., Vorona, S., Brochard, L., Ferguson, N. D., Goligher, E. C., Leung, C., Joynt, G., Wong, W., Lee, A., Gomersall, C., Poels, S., Casaer, M., Schetz, M., Van den Berghe, G., Meyfroidt, G., Holzgraefe, B., Von Kobyletzki, L. B., Cianchi, G., Becherucci, F., Batacchi, S., Cozzolino, M., Franchi, F., Di Valvasone, S., Ferraro, M. C., Peris, A., Phiphitthanaban, H., Wacharasint, P., Wongsrichanalai, V., Lertamornpong, A., Pengpinij, O., Wattanathum, A., Oer-areemitr, N., Boddi, M., Cappellini, E., Ciapetti, M., Di Lascio, G., Bonizzoli, M., Lazzeri, C., Katsin, M. L., Hurava, M. Y., Dzyadzko, A. M., Hermann, A., Schellongowski, P., Bojic, A., Riss, K., Robak, O., Lamm, W., Sperr, W., Staudinger, T., Buoninsegni, L. Tadini, Parodo, J., Ottaviano, A., Cecci, L., Corsi, E., Ricca, V., de Garibay, A. Perez Ruiz, Ende-Schneider, B., Schreiber, C., Kreymann, B., Turani, F., Resta, M., Niro, D., Castaldi, P., Boscolo, G., Gonsales, G., Martini, S., Belli, A., Zamidei, L., Falco, M., Lamas, T., Mendes, J., Galazzi, A., Benco, B., Binda, F., Masciopinto, L., Lissoni, A., Adamini, I., Thamjamrassri, T., Watcharotayangul, J., Numthavaj, P., Kongsareepong, S., Higuera, J., Cabestrero, D., Rey, L., Narváez, G., Blandino, A., Aroca, M., Saéz, S., De Pablo, R., Mohamed, A., Sklar, M., Munshi, L., Alban, L., Turrini, C., Taccone, P., Marenghi, C., Spadaro, S., Volta, C., Alonso, D. Cabestrero, González, L. Rey, Franci, A., Stocchi, G., Cappuccini, G., Socci, F., Guetti, C., Rastrelli, P., Nestorowicz, A., Glapinski, J., Fijalkowska-Nestorowicz, A., Wosko, J., Duprez, F., Bonus, T., Cuvelier, G., Mashayekhi, S., Ollieuz, S., Reychler, G., Kuchyn, I., Bielka, K., Sergienko, A., Jones, H., Day, C., Park, S. C., Yeom, S. R., Myatra, S. N., Gupta, S., Rajnala, V., Divatia, J., Silva, J. Villalobos, Olvera, O. Aguilera, Schulte, R. Cavazos, Bermudez, M. Castañeda, Zorrilla, L. Pariente, Ferretis, H. Lopez, García, K. Trejo, Balciuniene, N., Ramsaite, J., Kriukelyte, O., Krikscionaitiene, A., Tamosuitis, T., Terragni, P., Brazzi, L., Falco, D., Pistidda, L., Magni, G., Bartoletti, L., Mascia, L., Filippini, C., Ranieri, V., Kyriakoudi, A., Rovina, N., Koltsida, O., Konstantellou, E., Kardara, M., Kostakou, E., Gavriilidis, G., Vasileiadis, I., Koulouris, N., Koutsoukou, A., Van Snippenburg, W., Kröner, A., Flim, M., Buise, M., Hemler, R., Spronk, P., Noffsinger, B., Singh, B., Hockings, L., Spina, C., Magni, F., Di Giambattista, C., Vargiolu, A., Citerio, G., Scaramuzzo, G., Waldmann, A. D., Böhm, S. H., Ragazzi, R., Volta, C. A., Heines, S. J., Strauch, U., Van de Poll, M. C., Roekaerts, P. M., Bergmans, D. C., Sosio, S., Gatti, S., Punzi, V., Asta, A., Mroczka, J., Yaroshetskiy, A. I, Rezepov, N. A., Mandel, I. A., Gelfand, B. R., Ozen, E., Karakoc, E., Ayyildiz, A., Kara, S., Ekemen, S., Yelken, B. Buyukkidan, Saasouh, W., Freeman, J., Turan, A., Hajjej, Z., Sellami, W., Bousselmi, M., Samoud, W., Gharsallah, H., Labbene, I., Ferjani, M., Vetrugno, L., Barbariol, F., Forfori, F., Regeni, I., Della Rocca, G., Jansen, D., Jonkman, A., Doorduin, J., Roesthuis, L., Van der Hoeven, J., Heunks, L., Marocco, S. Arrigoni, Bottiroli, M., Pinciroli, R., Galanti, V., Calini, A., Gagliardone, M., Fumagalli, R., Ippolito, D., Sala, V. L., Meroni, V., Elbanna, M., Nassar, Y., Abdelmohsen, A., Yahia, M., Mongodi, S., Mojoli, F., Via, G., Tavazzi, G., Fava, F., Pozzi, M., Iotti, G. A., Bouhemad, B., Ruiz-Ferron, F., Simón, J. Serrano, Gordillo-Resina, M., Chica-Saez, V., Garcia, M. Ruiz, Vela-Colmenero, R., Redondo-Orts, M., Gontijo-Coutinho, C., Ozahata, T., Nocera, P., Franci, D., Santos, T., Carvalho-Filho, M., Fochi, O., Nacoti, M., Signori, D., Bonacina, D., Bonanomi, E., Bonvecchio, E., Stella, A., Roldi, E., Orlando, A., Luperto, M., Trunfio, D., Licitra, G., Martinelli, R., Vannini, D., Giuliano, G., Näslund, E., Lindberg, L. G., Lund, I., Frithiof, R., Nichols, A., Pentakota, S., Kodali, B., Pranskunas, A., Kiudulaite, I., Simkiene, J., Damanskyte, D., Pranskuniene, Z., Arstikyte, J., Vaitkaitis, D., Pilvinis, V., Brazaitis, M., Pool, R., Haugaa, H., Botero, A., Escobar, D., Maberry, D., Tønnessen, T., Zuckerbraun, B., Pinsky, M., Gomez, H., Lyons, H., Trimmings, A., Domizi, R., Scorcella, C., Damiani, E., Pierantozzi, S., Tondi, S., Monaldi, V., Carletti, A., Zuccari, S., Adrario, E., Pelaia, P., Donati, A., Kazune, S., Grabovskis, A., Volceka, K., Rubins, U., Bol, M., Suverein, M., Delnoij, T., Driessen, R., Heines, S., Delhaas, T., Vd Poll, M., Sels, J., Jozwiak, M., Chambaz, M., Sentenac, P., Richard, C., Monnet, X., Teboul, J. L., Bitar, Z., Maadarani, O., Al Hamdan, R., Huber, W., Malbrain, M., Chew, M., Mallat, J., Tagami, T., Hundeshagen, S., Wolf, S., Mair, S., Schmid, R., Aron, J., Adlam, M., Dua, G., Mu, L., Chen, L., Yoon, J., Clermont, G., Dubrawski, A., Duhailib, Z., Al Assas, K., Shafquat, A., Salahuddin, N., Donaghy, J., Morgan, P., Valeanu, L., Stefan, M., Provenchere, S., Longrois, D., Shaw, A., Mythen, M. G., Shook, D., Hayashida, D., Munson, S. H., Sawyer, A., Mariyaselvam, M., Blunt, M., Young, P., Nakwan, N., Khwannimit, B., Checharoen, P., Berger, D., Moller, P., Bloechlinger, S., Bloch, A., Jakob, S., Takala, J., Van den Brule, J. M., Stolk, R., Vinke, E., Van Loon, L. M., Pickkers, P., Van der Hoeven, J. G., Kox, M., Hoedemaekers, C. W., Werner-Moller, P., Bertini, P., Guarracino, F., Colosimo, D., Gonnella, S., Brizzi, G., Mancino, G., Baldassarri, R., Pinsky, M. R., Amitrano, D., Goslar, T., Stajer, D., Radsel, P., De Vos, R., Dijk, N. Bussink-van, Stringari, G., Cogo, G., Devigili, A., Graziadei, M. Ceola, Bresadola, E., Lubli, P., Amella, S., Marani, F., Polati, E., Gottin, L., Colinas, L., Hernández, G., Vicho, R., Serna, M., Canabal, A., Cuena, R., Gimenez, J., Mercado, P., Depret, F., Sassi, K., Herner, A., Abded, N., Elghonemi, M., Monir, A., Nikhilesh, J., Apurv, T., Uber, A. U., Grossestreuer, A., Moskowitz, A., Patel, P., Holmberg, M. J., Donnino, M. W., Graham, C. A., Hung, K., Lo, R., Leung, L. Y., Lee, K. H., Yeung, C. Y., Chan, S. Y., Trembach, N., Zabolotskikh, I., Caldas, J., Panerai, R., Camara, L., Ferreira, G., Almeida, J., de Oliveira, G. Queiroz, Jardim, J., Bor-Seng-Shu, E., Lima, M., Nogueira, R., Jatene, F., Zeferino, S., Galas, F., Robinson, T., Hajjar, L. A., Oliveira, M., Norgueira, R., Groehs, R., Ferreira-Santos, L., Oliveira, G., Hajjar, L., Ribeiro, J., Gaiotto, F., Lisboa, L., Fukushima, J., Rizk, S., Osawa, E., Franco, R., Kalil, R., Chlabicz, M., Sobkowicz, B., Kaminski, K., Kazimierczyk, R., Musial, W., Tycińska, A., Siranovic, M., Gopcevic, A., Gavranovic, Z. G., Horvat, A. H., Krolo, H., Rode, B., Videc, L., Trifi, A., Abdellatif, S., Ismail, K. Ben, Bouattour, A., Daly, F., Nasri, R., Lakhal, S. Ben, Beurton, A., Girotto, V., Galarza, L., Guedj, T., Iliæ, M. Karaman, Sakic, L., NN, V., Stojcic, L., Alphonsine, J., Lai, C., Tapanwong, N., Chuntupama, P., Hoellthaler, J., Lahmer, T., Latham, H., Bengtson, C. D., Satterwhite, L., Stites, M., Simpson, S. Q., Skladzien, T., Cicio, M., Garlicki, J., Serednicki, W., Wordliczek, J., Vargas, P., Salazar, A., Espinoza, M., Graf, J., Kongpolprom, N., Sanguanwong, N., Jonnada, S., Gerrard, C., Jones, N., Morley, T., Thorburn, P. T., Musaeva, T., Horst, S., Lipcsey, M., Kawati, R., Pikwer, A., Rasmusson, J., Castegren, M., Shilova, A., Yafarova, A., Gilyarov, M., Stojiljkovic, D. L. Loncar, Ulici, A., Reidt, S., Lam, T., Jancik, J., Ragab, D., Taema, K., Farouk, W., Saad, M., Liu, X., Uber, A., Montissol, S., Donnino, M., Andersen, L. W., Perlikos, F., Lagiou, M., Papalois, A., Kroupis, C., Toumpoulis, I., Carter, D., Sardo, S., Landoni, G., Kongsayreepong, S., Sungsiri, R., Wongsripunetit, P., Marchio, P., Guerra-Ojeda, S., Gimeno-Raga, M., Mauricio, M. D., Valles, S. L., Aldasoro, C., Jorda, A., Aldasoro, M., Vila, J. M., Borg, U. B., Neitenbach, A. M., García, M., González, P. Guijo, Romero, M. Gracia, Orduña, P. Saludes, Cano, A. Gil, Rhodes, A., Grounds, R. M., Cecconi, M., Lee, C., Hatib, F., Jian, Z., Rinehart, J., De Los Santos, J., Canales, C., Cannesson, M., García, M. I. Monge, Scheeren, T., Chantziara, V., Vassi, A., Michaloudis, G., Sanidas, E., Golemati, S., Bateman, R. M., Mokhtar, A., Omar, W., Aziz, K. Abdel, El Azizy, H., Nielsen, D. L. Lykke, Holler, J. G., Lassen, A., Eriksson, M., Strandberg, G., Capoletto, C., Nakamura, R., Risk, S., Park, C., Dias, F., D’Arrigo, N., Fortuna, F., Redaelli, S., Zerman, L., Becker, L., Serrano, T., Cotes, L., Ramos, F., Fadel, L., Coelho, F., Mendes, C., Real, J., Pedron, B., Kuroki, M., Costa, E., and Azevedo, L.

Subjects
Critical Care and Intensive Care Medicine, Meeting Abstracts
Published
2017

4. Chlorpromazine overcomes temozolomide resistance in glioblastoma by inhibiting Cx43 and essential DNA repair pathways.

Author

Matarrese P, Signore M, Ascione B, Fanelli G, Paggi MG, and Abbruzzese C

Subjects
Humans, Cell Line, Tumor, Gene Expression Regulation, Neoplastic drug effects, Drug Synergism, Brain Neoplasms drug therapy, Brain Neoplasms pathology, Brain Neoplasms genetics, Chlorpromazine pharmacology, Chlorpromazine therapeutic use, Temozolomide pharmacology, Temozolomide therapeutic use, Glioblastoma drug therapy, Glioblastoma pathology, Glioblastoma genetics, DNA Repair drug effects, Connexin 43 metabolism, Connexin 43 genetics, Drug Resistance, Neoplasm drug effects, Drug Resistance, Neoplasm genetics
Abstract

Background: In the fight against GBM, drug repurposing emerges as a viable and time-saving approach to explore new treatment options. Chlorpromazine, an old antipsychotic medication, has recently arisen as a promising candidate for repositioning in GBM therapy in addition to temozolomide, the first-line standard of care. We previously demonstrated the antitumor efficacy of chlorpromazine and its synergistic effects with temozolomide in suppressing GBM cell malignant features in vitro. This prompted us to accomplish a Phase II clinical trial to evaluate the efficacy and safety of adding chlorpromazine to temozolomide in GBM patients with unmethylated MGMT gene promoter. In this in vitro study, we investigate the potential role of chlorpromazine in overcoming temozolomide resistance., Methods: In our experimental set, we analyzed Connexin-43 expression at both the transcriptional and protein levels in control- and chlorpromazine-treated GBM cells. DNA damage and subsequent repair were assessed by immunofluorescence of γ-H2AX and Reverse-Phase Protein microArrays in chlorpromazine treated GBM cell lines. To elucidate the relationship between DNA repair systems and chemoresistance, we analyzed a signature of DNA repair genes in GBM cells after treatment with chlorpromazine, temozolomide and Connexin-43 downregulation., Results: Chlorpromazine treatment significantly downregulated connexin-43 expression in GBM cells, consequently compromising connexin-dependent cellular resilience, and ultimately contributing to cell death. In line with this, we observed concordant post-translational modifications of molecular determinants involved in DNA damage and repair pathways. Our evaluation of DNA repair genes revealed that temozolomide elicited an increase, while chlorpromazine, as well as connexin-43 silencing, a decrease in DNA repair gene expression in GBM cells., Conclusions: Chlorpromazine potentiates the cytotoxic effects of the alkylating agent temozolomide through a mechanism involving downregulation of Cx43 expression and disruption of the cell cycle arrest essential for DNA repair processes. This finding suggests that chlorpromazine may be a potential therapeutic strategy to overcome TMZ resistance in GBM cells by inhibiting their DNA repair mechanisms., (© 2024. The Author(s).)

Published
2024
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5. Chlorpromazine induces cytotoxic autophagy in glioblastoma cells via endoplasmic reticulum stress and unfolded protein response.

Author

Matteoni S, Matarrese P, Ascione B, Ricci-Vitiani L, Pallini R, Villani V, Pace A, Paggi MG, and Abbruzzese C

Subjects
Chlorpromazine pharmacology, Dopamine Antagonists pharmacology, Glioblastoma mortality, Humans, Survival Analysis, Autophagy genetics, Chlorpromazine therapeutic use, Dopamine Antagonists therapeutic use, Endoplasmic Reticulum Stress drug effects, Glioblastoma drug therapy, Unfolded Protein Response drug effects
Abstract

Background: Glioblastoma (GBM; grade IV glioma) is characterized by a very short overall survival time and extremely low 5-year survival rates. We intend to promote experimental and clinical research on rationale and scientifically driven drug repurposing. This may represent a safe and often inexpensive way to propose novel pharmacological approaches to GBM. Our precedent work describes the role of chlorpromazine (CPZ) in hindering malignant features of GBM. Here, we investigate in greater detail the molecular mechanisms at the basis of the effect of CPZ on GBM cells., Methods: We employed proteomics platforms, i.e., activity-based protein profiling plus mass spectrometry, to identify potential cellular targets of the drug. Then, by means of established molecular and cellular biology techniques, we assessed the effects of this drug on GBM cell metabolic and survival pathways., Results: The experimental output indicated as putative targets of CPZ several of factors implicated in endoplasmic reticulum (ER) stress, with consequent unfolded protein response (UPR). Such a perturbation culminated in a noticeable reactive oxygen species generation and intense autophagic response that resulted in cytotoxic and abortive effects for six GBM cell lines, three of which growing as neurospheres, while it appeared cytoprotective for the RPE-1 human non-cancer neuro-ectodermal cell line., Conclusions: This discrepancy could be central in explaining the lethal effects of the drug on GBM cells and the relatively scarce cytotoxicity toward normal tissues attributed to this compound. The data presented here offer support to the multicenter phase II clinical trial we have undertaken, which consists of the addition of CPZ to first-line treatment of GBM patients carrying a hypo- or un-methylated MGMT gene, i.e. those characterized by intrinsic resistance to temozolomide., (© 2021. The Author(s).)

Published
2021
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6. Repurposing chlorpromazine in the treatment of glioblastoma multiforme: analysis of literature and forthcoming steps.

Author

Abbruzzese C, Matteoni S, Persico M, Villani V, and Paggi MG

Subjects
Chlorpromazine pharmacology, Drug Repositioning, Female, Humans, Male, Brain Neoplasms drug therapy, Chlorpromazine therapeutic use, Glioblastoma drug therapy
Abstract

Background: Glioblastoma multiforme is a CNS cancer characterized by diffuse infiltrative growth, aggressive clinical behavior and very poor prognosis. The state-of-art clinical approach to this disease consists of surgical resection followed by radiotherapy plus concurrent and adjuvant chemotherapy with temozolomide. Tumor recurrence occurs in virtually all cases, therefore, despite any treatment, the median survival is very low (14.6 months), which makes the approach to these patients a challenging clinical issue., Main Body: The escalating costs and times required for new medications to reach the bedside make repurposing or repositioning of old drugs, when scientific bases allow their use in other pathologies, an appealing strategy. Here, we analyze a number of literature data concerning the antipsychotic chlorpromazine, the founder of the phenothiazines class of drugs, a medication widely used in the clinics for approximately 60 years. The drug exerts its effects on psychiatric patients by interfering with the dopamine receptor D 2 , although more recent pharmacodynamics studies ascribe chlorpromazine a series of biological effects on cancer cells, all converging in hindering also glioblastoma survival capabilities., Short Conclusions: On these bases, and assisted by the information on the well-established chlorpromazine toxicity and dosage in humans, we designed a Phase II clinical trial involving the combination of chlorpromazine with the standard treatment, temozolomide, in the adjuvant phase of the therapeutic protocol. Patients displaying hypo-methylation of the MGMT gene, and thus intrinsically resistant to temozolomide, will be enrolled. The endpoints of this study are the analysis of toxicity and clinical activity, as evaluated in terms of Progression-Free Survival, of the association of chlorpromazine with the first-line treatment for this very serious form of cancer.

Published
2020
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7. The kinase inhibitor SI113 induces autophagy and synergizes with quinacrine in hindering the growth of human glioblastoma multiforme cells.

Author

Matteoni S, Abbruzzese C, Matarrese P, De Luca G, Mileo AM, Miccadei S, Schenone S, Musumeci F, Haas TL, Sette G, Carapella CM, Amato R, Perrotti N, Signore M, and Paggi MG

Subjects
Apoptosis drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Drug Synergism, Glioblastoma genetics, Glioblastoma pathology, Humans, Neoplasm Proteins genetics, Protein Kinase Inhibitors pharmacology, Signal Transduction drug effects, Autophagy drug effects, Glioblastoma drug therapy, Pyrazoles pharmacology, Pyrimidines pharmacology, Quinacrine pharmacology
Abstract

Background: Glioblastoma multiforme (GBM), due to its location, aggressiveness, heterogeneity and infiltrative growth, is characterized by an exceptionally dismal clinical outcome. The small molecule SI113, recently identified as a SGK1 inhibitor, has proven to be effective in restraining GBM growth in vitro and in vivo, showing also encouraging results when employed in combination with other antineoplastic drugs or radiotherapy. Our aim was to explore the pharmacological features of SI113 in GBM cells in order to elucidate the pivotal molecular pathways affected by the drug. Such knowledge would be of invaluable help in conceiving a rational offensive toward GBM., Methods: We employed GBM cell lines, either established or primary (neurospheres), and used a Reverse-Phase Protein Arrays (RPPA) platform to assess the effect of SI113 upon 114 protein factors whose post-translational modifications are associated with activation or repression of specific signal transduction cascades., Results: SI113 strongly affected the PI3K/mTOR pathway, evoking a pro-survival autophagic response in neurospheres. These results suggested the use of SI113 coupled, for maximum efficiency, with autophagy inhibitors. Indeed, the association of SI113 with an autophagy inhibitor, the antimalarial drug quinacrine, induced a strong synergistic effect in inhibiting GBM growth properties in all the cells tested, including neurospheres., Conclusions: RPPA clearly identified the molecular pathways influenced by SI113 in GBM cells, highlighting their vulnerability when the drug was administered in association with autophagy inhibitors, providing a strong molecular rationale for testing SI113 in clinical trials in associative GBM therapy.

Published
2019
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8. Drug repurposing for the treatment of glioblastoma multiforme.

Author

Abbruzzese C, Matteoni S, Signore M, Cardone L, Nath K, Glickson JD, and Paggi MG

Subjects
Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Brain Neoplasms genetics, Brain Neoplasms metabolism, Clinical Trials as Topic, Drug Repositioning, Energy Metabolism drug effects, Gene Regulatory Networks drug effects, Glioblastoma genetics, Glioblastoma metabolism, Humans, Structure-Activity Relationship, Antineoplastic Agents therapeutic use, Brain Neoplasms drug therapy, Glioblastoma drug therapy
Abstract

Background: Glioblastoma Multiforme is the deadliest type of brain tumor and is characterized by very poor prognosis with a limited overall survival. Current optimal therapeutic approach has essentially remained unchanged for more than a decade, consisting in maximal surgical resection followed by radiotherapy plus temozolomide., Main Body: Such a dismal patient outcome represents a compelling need for innovative and effective therapeutic approaches. Given the development of new drugs is a process presently characterized by an immense increase in costs and development time, drug repositioning, finding new uses for existing approved drugs or drug repurposing, re-use of old drugs when novel molecular findings make them attractive again, are gaining significance in clinical pharmacology, since it allows faster and less expensive delivery of potentially useful drugs from the bench to the bedside. This is quite evident in glioblastoma, where a number of old drugs is now considered for clinical use, often in association with the first-line therapeutic intervention. Interestingly, most of these medications are, or have been, widely employed for decades in non-neoplastic pathologies without relevant side effects. Now, the refinement of their molecular mechanism(s) of action through up-to-date technologies is paving the way for their use in the therapeutic approach of glioblastoma as well as other cancer types., Short Conclusion: The spiraling costs of new antineoplastic drugs and the long time required for them to reach the market demands a profoundly different approach to keep lifesaving therapies affordable for cancer patients. In this context, repurposing can represent a relatively inexpensive, safe and fast approach to glioblastoma treatment. To this end, pros and cons must be accurately considered.

Published
2017
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9. Hepatitis C virus core protein modulates pRb2/p130 expression in human hepatocellular carcinoma cell lines through promoter methylation.

Author

Mileo AM, Mattarocci S, Matarrese P, Anticoli S, Abbruzzese C, Catone S, Sacco R, Paggi MG, and Ruggieri A

Subjects
Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular metabolism, Cell Cycle genetics, Cell Line, Tumor, CpG Islands, Epigenesis, Genetic, Gene Expression, Gene Silencing, Hepatitis C Antigens genetics, Humans, Intracellular Space metabolism, Liver Neoplasms genetics, Liver Neoplasms metabolism, Multigene Family, Protein Transport, Retinoblastoma Protein genetics, Retinoblastoma Protein metabolism, Retinoblastoma-Like Protein p130 metabolism, Viral Core Proteins genetics, DNA Methylation, Gene Expression Regulation, Hepatitis C Antigens metabolism, Promoter Regions, Genetic, Retinoblastoma-Like Protein p130 genetics, Viral Core Proteins metabolism
Abstract

Background: Hepatitis C Virus (HCV) infection is associated with chronically evolving disease and development of hepatocellular carcinoma (HCC), albeit the mechanism of HCC induction by HCV is still controversial. The nucleocapsid (core) protein of HCV has been shown to be directly implicated in cellular transformation and immortalization, enhancing the effect of oncogenes and decreasing the one of tumor suppressor genes, as RB1 and its protein product pRB. With the aim of identifying novel molecular mechanisms of hepatocyte transformation by HCV, we examined the effect of HCV core protein on the expression of the whole Retinoblastoma (RB) family of tumor and growth suppressor factors, i.e. pRb, p107 and pRb2/p130., Methods: We used a model system consisting of the HuH-7, HCV-free, human hepatocellular carcinoma cell line and of the HuH-7-CORE cells derived from the former and constitutively expressing the HCV core protein. We determined pRb, p107 and pRb2/p130 protein and mRNA amount of the respective genes RB1, RBL1 and RBL2, RBL2 promoter activity and methylation as well as DNA methyltransferase 1 (DNMT1) and 3b (DNMT3b) expression level. The effect of pRb2/p130 over-expression on the HCV core-expressing HuH-7-CORE cells was also evaluated., Results: We found that the HCV core protein expression down-regulated pRb2/p130 protein and mRNA levels in HuH-7-CORE cells by inducing promoter hyper-methylation with the concomitant up-regulation of DNMT1 and DNMT3b expression. When pRb2/p130 expression was artificially re-established in HuH-7-CORE cells, cell cycle analysis outlined an accumulation in the G0/G1 phase, as expected., Conclusions: HCV core appears indeed able to significantly down-regulate the expression and the function of two out of three RB family tumor and growth suppressor factors, i.e. pRb and pRb2/p130. The functional consequences at the level of cell cycle regulation, and possibly of more complex cell homeostatic processes, may represent a plausible molecular mechanism involved in liver transformation by HCV.

Published
2015
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10. Determination of SGK1 mRNA in non-small cell lung cancer samples underlines high expression in squamous cell carcinomas.

Author

Abbruzzese C, Mattarocci S, Pizzuti L, Mileo AM, Visca P, Antoniani B, Alessandrini G, Facciolo F, Amato R, D'Antona L, Rinaldi M, Felsani A, Perrotti N, and Paggi MG

Subjects
Aged, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell pathology, Disease-Free Survival, Female, Gene Expression Regulation, Neoplastic, Humans, Immediate-Early Proteins genetics, Lung Neoplasms genetics, Lung Neoplasms pathology, Male, Middle Aged, Neoplasm Staging, Prognosis, Protein Serine-Threonine Kinases genetics, RNA, Messenger genetics, RNA, Messenger metabolism, Signal Transduction, Carcinoma, Non-Small-Cell Lung metabolism, Carcinoma, Squamous Cell metabolism, Immediate-Early Proteins metabolism, Lung Neoplasms metabolism, Protein Serine-Threonine Kinases metabolism
Abstract

Background: Lung cancer represents the most frequent cause of death for cancer. In non-small cell lung cancer (NSCLC), which accounts for the vast majority of this disease, only early detection and treatment, when possible, may significantly affect patient's prognosis. An important role in NSCLC malignancy is attributed to the signal transduction pathways involving PI3Kinase, with consequent activation of the AKT family factors. The serum and glucocorticoid kinase (SGK) factors, which share high structural and functional homologies with the AKT factors, are a family of ubiquitously expressed serine/threonine kinases under the control of cellular stress and hormones. SGK1 is the most represented SGK member., Methods: By means of immunohistochemistry and quantitative real-time PCR, we determined SGK1 protein and mRNA expression in a cohort of 66 formalin-fixed, paraffin-embedded NSCLC surgical samples. All samples belonged to patients with a well-documented clinical history., Results: mRNA expression was significantly higher in squamous cell carcinomas, and correlated with several clinical prognostic indicators, being elevated in high-grade tumors and in tumors with bigger size and worse clinical stage. No correlation was found between SGK1 protein expression and these clinical parameters., Conclusions: This explorative analysis of SGK1 expression in NSCLC samples highlights the potential role of this factor in NSCLC patients' prognosis. Moreover, the higher expression in the squamous cell carcinoma subtype opens new therapeutic possibilities in this NSCLC subtype by designing specific kinase inhibitors.

Published
2012
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