Search

Your search keyword '"Sisto, F."' showing total 13 results
Start Over Author "Sisto, F." Database OpenAIRE
13 results on '"Sisto, F."'

1. Identification and characterization of the a-CA in the outer membrane vesicles produced by Helicobacter pylori

Author

Ronci M, Del Prete S, Puca V, Carradori S, Carginale V, Muraro R, Mincione G, Aceto A, Sisto F, Supuran CT, Grande R, and Capasso C.

Subjects
Carbonic anydrases, biofilm, mass spectrometry, outer membrane vesicles (OMVs), protonography
Abstract

The genome of Helicobacter pylori encodes for carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the ?- and ?-CA classes, which together with urease, have a pivotal role in the acid acclimation of the microorganism within the human stomach. Recently, in the exoproteome of H. pylori, a CA with no indication of the corresponding class was identified. Here, using the protonography and the mass spectrometry, a CA belonging to the ?-class was detected in the outer membrane vesicles (OMVs) generated by planktonic and biofilm phenotypes of four H. pylori strains. The amount of this metalloenzyme was higher in the planktonic OMVs (pOMVs) than in the biofilm OMVs (bOMVs). Furthermore, the content of ?-CA increases over time in the pOMVs. The identification of the ?-CA in pOMVs and bOMVs might shed new light on the role of this enzyme in the colonization, survival, persistence, and pathogenesis of H. pylori.

Published
2019
Full Text
View/download PDF

4. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes

Author

Tricoci, P, Huang, Z, Held, C, Moliterno, Dj, Armstrong, Pw, Van de Werf, F, White, Hd, Aylward, Pe, Wallentin, L, Chen, E, Lokhnygina, Y, Pei, J, Leonardi, S, Rorick, Tl, Kilian, Am, Jennings, Lh, Ambrosio, G, Bode, C, Cequier, A, Cornel, Jh, Diaz, R, Erkan, A, Huber, K, Hudson, Mp, Jiang, L, Jukema, Jw, Lewis, Bs, Lincoff, Am, Montalescot, G, Nicolau, Jc, Ogawa, H, Pfisterer, M, Prieto, Jc, Ruzyllo, W, Sinnaeve, Pr, Storey, Rf, Valgimigli, M, Whellan, Dj, Widimsky, P, Strony, J, Harrington, Ra, Mahaffey, Kw, Huo, Y, Lixin, J, Isaza, D, Grande, P, Laine, M, Wong, L, Ofner, P, Yamaguchi, T, Park, Sj, Nordrehaug, Je, Providencia, L, Cheem, Th, Dalby, A, Betriu, A, Chen, Mf, Verheugt, F, Frye, Rl, Hochman, J, Steg, Pg, Bailey, Kr, Easton, Jd, Lincoff, A, Underwood, Fd, Wrestler, J, Larson, D, Vandyne, B, Kilian, A, Harmelin-Kadouri, R, Layton, L, Lipka, L, Petrauskas, S, Qidwai, M, Sorochuck, C, Temple, T, Mason, D, Sydlowski, D, Gallagher, B, Villasin, A, Beernaert, A, Douglas, S, Garrett, J, Wiering, J, Adriaenssens, T, Ganame, J, Hulselmans, M, Katz, Jn, Kayaert, P, La Gerche, A, Onsea, K, Zalewski, J, Johnson, A, O'Briant, J, Smith, M, Akerblom, A, Armaganijan, L, Bertolami, A, Brennan, M, da Ponte Nacif SA, de Campos Gonzaga, C, Dequadros, A, Déry, Jp, Dev, S, Ducrocq, G, Eapen, Zp, Echenique, L, Eggers, K, Garcia, H, Guimaraes, Hp, Hagstrom, E, Hanet, C, James, S, Jonelid, B, Kolls, Bj, Leiria, T, Leite, R, Lombardi, C, Lopes, Rd, Malagutti, P, Mathews, R, Mehta, Rh, Melloni, C, Piccini, Jp, Rodriques Soares, P, Roe, Mt, Shah, Br, Stashenko, G, Szczech, La, Truffa, A, Varenhorst, C, Vranckx, P, Williams, J, Kilaru, R, White, Ja, Binkowitz, B, He, W, Ramos, Ms, Hasbani, E, Farras, Ha, Luz del Valle, L, Zapata, G, Centeno, Ep, Hominal, M, Beloscar, J, Panno, M, Berli, M, Carlevaro, O, Wasserman, T, Lembo, L, Diez, F, Bettinotti, M, Allall, O, Macin, S, Hii, C, Bett, N, Aroney, C, Roberts-Thomson, P, Arstall, M, Horowitz, J, Prasan, A, Farshid, A, Rankin, J, Duffy, S, Sinhal, A, Hendricks, R, Waites, J, Hill, A, French, J, Adams, M, Soward, A, Dick, R, Jepson, N, Nelson, G, Thompson, P, Neunteufl, T, Pachinger, O, Leisch, F, Siostrzonek, P, Roithinger, F, Pieske, B, Weber, H, Eber, B, Zenker, G, Sinnaeve, P, Roosen, J, Vervoort, G, Coussement, P, Striekwold, H, Boland, J, Van Dorpe, A, Dujardin, K, Mertens, D, Vanneste, L, Celen, H, Lesseliers, H, Vrolix, M, Leone, A, De Maeseneire, S, Hellemans, S, Silva, Fa, Franken, M, Moraes JB Jr, Mora, R, Michalaros, Y, Perin, M, Guimaraes, Ae, da Silva DG, Mattos, Ma, Alves AR Jr, Hernandes, Me, Golin, V, da Silva SA, Ardito, W, Dery, Jp, Mukherjee, A, Tanguay, Jf, Kornder, J, Lutchmedial, S, Degrace, M, Klinke, P, Constance, C, Nogareda, G, Wong, G, Macdonald, P, Senaratne, M, Rupka, D, Halperin, F, Ramanathan, K, Natarajan, M, Lai, C, Brossoit, R, Tymchak, W, Rose, B, Dupuis, R, Mansour, S, Bata, I, Zadra, R, Turek, M, Madan, M, Le May, M, Leon, L, Perez, L, Yovaniniz, P, Pedemonte, O, Campos, P, Pincetti, C, Sepulveda, P, Li, W, Zhao, R, Li, Z, Yang, Y, Chen, J, Li, H, Jiang, Y, Li, D, Qu, P, Sun, Y, Zheng, Y, Zhou, C, Zhang, F, Wei, M, Wang, D, Lemus, J, Fernandez, Rl, Jaramillo, C, Ochoa, J, Velez, S, Cano, N, Lutz, J, Botero, R, Jaramillo, M, Saaib, J, Sanchez, G, Hernandez, H, Mendoza, F, Rizcala, A, Urina, M, Polasek, R, Motovska, Z, Zemanek, D, Ostransky, J, Kettner, J, Spinar, J, Groch, L, Ramik, C, Stumar, J, Linhart, A, Pleva, L, Niedobova, E, Macha, J, Vojacek, J, Stipal, R, Galatius, S, Eggert, S, Mickley, H, Egstrup, K, Pedersen, O, Hvilsted, L, Sykulski, R, Skagen, K, Dodt, K, Klarlund, K, Husted, S, Jensen, G, Melchior, T, Sjoel, A, Steffensen, Fh, Airaksinen, Ke, Laukkanen, Ja, Syvanne, Ms, Kotila, Mj, Mikael, K, Naveri, Hk, Hekkala, Am, Mustonen, Jn, Halkosaari, M, Ohlmann, P, Khalife, K, Dibon, O, Hirsch, Jl, Furber, A, Nguyen-Khac, Jo, Delarche, N, Probst, V, Lim, P, Bayet, G, Dauphin, R, Levai, L, Galinier, M, Belhassane, A, Wiedemann, Jy, Fouche, R, Coisne, D, Henry, P, Schiele, F, Boueri, Z, Vaquette, B, Davy, Jm, Cottin, Y, D'Houdain, F, Danchin, N, Cassat, C, Messner, P, Elbaz, M, Coste, P, Zemour, G, Maupas, E, Feldman, L, Soto, Fx, Ferrari, E, Haltern, G, Heuer, H, Genth-Zotz, S, Loges, C, Stellbrink, C, Terres, W, Ferrar, M, Zeymer, U, Brachmann, J, Mudra, H, Vohringer, Hf, vom Dah, J, Kreuzer, J, Hill, S, Kleinertz, K, Kadel, C, Appel, Kf, Nienabe, C, Behrens, S, Frantz, S, Mehrhof, F, Krings, P, Hengstenberg, C, Lueders, S, Hanefel, C, Krulls-Munch, J, Dorse, T, Leschke, M, Nogai, K, Butter, C, Darius, H, Fichtlscherer, Hp, Schmitt, C, Kasisk, Hp, Dorr, M, Fran, N, Jereczek, M, Wiemer, M, Nickenig, G, Boudriot, E, Werner, G, Altila, T, Strasser, R, Baldus, S, Desaga, M, Buerke, M, Land, S, Schunkert, H, Schulze, Ho, Holmer, S, Sohn, Hy, Burkhardt, W, Lauer, B, Schwimmbeck, P, Schoeller, R, Lapp, H, Gross, M, Kindermann, I, Schuster, P, Yu, Cm, Lee, S, Merkely, B, Apro, D, Lupkovics, G, Edes, I, Ungi, I, Piroth, Z, Csapo, K, Dezsi, Ca, Herczeg, B, Sereg, M, Butnaru, A, Lewis, B, Rosenschein, U, Mosseri, M, Turgeman, Y, Pollak, A, Shotan, A, Hammerman, H, Rozenman, Y, Gottlieb, S, Atar, S, Weiss, A, Marmor, A, Iakobishvili, Z, Mascia, F, De Cesare, N, Piovaccari, G, Ceravolo, R, Fiscella, A, Salvioni, A, Silvestri, O, Moretti, L, Severi, S, Carmina, Mg, De Caterina, R, Fattore, L, Terrosu, P, Trimarco, B, Ardissino, D, Uguccioni, L, Auguadro, C, Gregorio, G, De Ferrari, G, Testa, R, Evola, R, De Servi, S, Sganzerla, P, Vassanelli, C, Brunelli, C, Scherillo, M, Tamburino, C, Limido, A, Luzza, F, Percoco, Gf, Sinagra, G, Volpe, M, Crea, F, Fedele, F, Rasetti, G, Cinelli, F, Merlini, P, Sisto, F, Biancoli, S, Fresco, C, Corrada, E, Casolo, G, Santini, M, D'Alessandro, B, Antoniucci, D, Tuccillo, B, Assennato, P, Puccioni, E, Pasquetto, G, Perna, Gp, Morgagni, G, Takizawa, K, Kato, K, Oshima, S, Yagi, M, Asai, T, Kamiya, H, Hirokami, M, Sakota, S, Sueyoshi, A, Shimomura, H, Hashimoto, T, Miyahara, M, Matsumura, T, Nakao, K, Kakuta, T, Nakamura, S, Nishi, Y, Kawajiri, K, Nagai, Y, Takahashi, A, Ikari, Y, Hara, K, Koga, T, Fujii, K, Tobaru, T, Tsunoda, R, Uchiyama, T, Hirayama, H, Fujimoto, K, Sakurai, S, Tanigawa, T, Ohno, M, Yamamoto, E, Ikuta, S, Kato, A, Kikuta, K, Takami, A, Chong, Wp, Ong, Tk, Yusof, A, Maskon, O, Kahar, A, Breedveld, Rw, Bendermacher, Pe, Hamer, Bj, Oude Ophuis AJ, Nierop, Pr, Westendorp, Ic, Beijerbacht, Hp, Herrman, Jp, van 't Hof AW, Troquay, Rp, van der Meer, P, Peters, Rh, van Rossum, P, Liem, A, Pieterse, Mg, van Eck JW, van der Zwaan, C, Pasupati, S, Elliott, J, Tisch, J, Hart, H, Luke, R, Scott, D, Ternouth, I, White, H, Hamer, A, Harding, S, Wilkins, G, O'Meeghan, T, Harrison, N, Nilsen, D, Thalamus, J, Aaberge, L, Brunvand, H, Lutterbey, G, Omland, Tm, Eritsland, J, Wiseth, R, Aase, O, Campos, C, Horna, M, Toce, L, Salazar, M, Przewlocki, T, Ponikowski, P, Kasprzak, J, Kopaczewski, J, Musial, W, Mazurek, W, Kawecka-Jaszcz, K, Pluta, W, Dobrzycki, S, Loboz-Grudzien, K, Lewczuk, J, Karwowski, D, Grajek, S, Dudek, D, Trusz-Gluza, M, Kornacewicz-Jach, Z, Gil, R, Ferreira, J, Gavina, C, Ferreira, R, Martins, D, Garcia-Rinaldi, R, Ufret, R, Vazquez-Tanus, J, Banchs, H, Wong, A, Tan, Hc, Guerra, M, Ebrahim, I, Roux, J, Blomerus, P, Saaiman, A, Corbett, C, Pillay, T, Freeman, V, Horak, A, Zambakides, C, Burgess, L, Yoon, Jh, Ahn, Th, Gwon, Hc, Seong, Iw, Kim, Hs, Jeong, Mh, Kim, Yd, Chae, Sc, Hernandez, Jm, Pique, M, Fernandez Portales, J, Paz, Ma, Lopez Palop, R, Iniguez, A, Diaz Fernandez, J, Alvarez, P, Sanz, E, Heras, M, Sala, J, Goicolea, J, Cruz Fernandez, J, Serra, A, Fernandez Ortiz, A, Calle, G, Barriales, V, Albarran, A, Curos, A, Molano Casimiro FJ, Suarez, Ma, Franco, Sn, Bayon, J, Suarez, J, Belchi, J, Moreu, J, San Martin, M, Melgares Moreno, R, Aguirre Salcedo, J, Gonzalez Juanatey JR, Martinez Romero, P, Galache Osuna JG, Albertsson, P, Diderholm, E, Lycksell, M, Rasmanis, G, Swahn, E, Cherfan, P, Christensen, K, Lundman, P, Larson, Le, Vasko, P, Pripp, Cm, Johansson, A, Moccetti, T, Corti, R, Pieper, M, Mach, F, Eberli, F, Jeger, R, Rickli, H, Vogt, P, Windecker, S, Wu, Cj, Kao, Hl, Charng, Mj, Chang, Kc, Chen, Zc, Tsa, Cd, Shyu, Kg, Lai, Wt, Hsieh, Ic, Hou, Jy, Yeh, Hi, Ueng, Kc, Yin, Wh, Timurkaynak, T, Yigit, Z, Yilmaz, M, Boyaci, A, Sahin, M, Goktekin, O, Bozkurt, E, Ercan, E, Yildirir, A, Muthusamy, R, Keeling, P, Levy, T, Zaman, A, Cohen, A, Gorog, D, Baumbach, A, Oldroyd, K, Kadr, H, Tait, G, Bellenger, N, Davis, G, Shakespeare, C, Senior, R, Bruce, D, Uren, N, Trouton, T, Ahsan, A, Hamed, A, Malik, I, Sarma, J, Millar-Craig, M, Robson, H, Kennon, S, Sprigings, D, Brodie, B, Kang, Gs, Thomas, G, Cheng, Sc, Espinoza, A, Kassas, S, Jafar, Z, Kumar, P, Izzo, M, Wiseman, A, Chandna, H, Felten, W, D'Urso, M, Gudipati, Cr, Coram, R, Gill, S, Bengtson, J, Chang, M, Raisinghani, A, Blankenship, J, Harbor, Wf, Kraft, P, Ashraf, R, Chambers, J, Albirini, A, Malik, A, Ziada, K, Slepian, M, Taussig, A, Vernon, H, Jetty, P, Islam, Ma, Canaday, D, Martin, T, Burchenal, Jj, Gencheff, N, Nygaard, T, Panchal, V, Merritt, R, Abrahams, L, Lambert, C, Reyes, P, Leimbach, W, Chhabra, A, Caputo, R, Imburgia, M, Erickson, B, Kleiman, N, Hunter, J, Dehning, M, Graham, B, Strain, J, White, Jk, Mcgarvey, J Jr, Henderson, D, Treasure, C 2nd, Mirro, M, Pancholy, S, Helmy, T, Westerhausen, D, Dib, N, Penny, W, Kim, H, Degregorio, M, Jay, D, Kmonicek, J, Berlowitz, M, Starling, M, Langevin, E, Nelson, R, Singer, A, Siachos, A, Gibson, G, Parrott, C, Held, J, Puleo, P, Wolford, T, Omar, B, Brilakis, E, Lewis, S, Heller, L, Brener, S, Addo, T, Lieberman, S, Eisenberg, D, Feldman, R, Waksman, R, Waltman, J, Schulman, S, Bounds, C, Voyce, S, Batchelor, W, Dobies, D, Pasnoori, V, Chandrashekhar, Y, Vetrovec, G, Azrin, M, Spriggs, D, Hirsch, C, Smucker, M, Chetcuti, S, Stella, R, Levite, H, Shoukfeh, M, Vidovich, M, Saucedo, J, Fintel, D, Low, R, Gellman, J, Ahsan, C, Unks, Dm, Tolleson, T, Ceccoli, H, Aggarwal, K, Bhaktaram, V, Olson, C, Decaro, M, Kaluski, E, Mehta, V, Puma, J, Singh, V, Fulmer, J, Lewis, D, Khadra, S, Staniloae, C, East, M, Sundram, Ps, Anderson, J, Wasserman, H, Guy, D, Brill, D, Kruse, K, Ebrahimi, R, Nguyen, T, Keating, F, Srivastava, R, Wassmer, P, Todd, J 3rd, Stein, M, Hamzeh, I, Laxson, D, Hodson, R, Puri, S, Vijayaraghavan, K, Gazmuri, R, Chu, A, Vijay, N, Rabinowitz, A, Block, T, Agarwal, H, Martin, J, Zetterlund, P, Fortuin, D, Macdonell, A 3rd, Zouzoulas, S, Chepuri, V, Schmalfuss, C, Karve, M, Aviles, R, Lieberman, E, Amlani, M, Murphy, S, Shapiro, T, Herzog, E, Ariani, K, Bhagwat, R, Hockstad, E, Kai, W, Saririan, M, Roth, R, Weiland, F, Atassi, K, Harjai, K, Muhlestein, J, Marsh, R, Shokooh, S, Nahhas, A, Labroo, A, Mayor, M, Koshy, S, Tariq, M, Rayos, G, Jones, S, Klugherz, B, Dewey, R, Rashid, Hu, Wohns, D, Feiring, A, Bowles, M, Rohrbeck, S, Monroe, Vs, De Gottlieb, A, Gumm, D, Brown, C 3rd, Chang, D, Kalaria, V, Minisi, A, Joumaa, M, Josephson, R, Kleczka, J, Silver, K, Coleman, P, Brachfeld, C, Saltiel, F, Reiner, J, Carell, E, Hanovich, G, Rosenberg, M, Das, G, Blick, D, and Universitat de Barcelona

Subjects
Male, Pyridines, medicine.medical_treatment, Kaplan-Meier Estimate, law.invention, Lactones, Randomized controlled trial, law, Thrombin receptor antagonist, clopidogrel, placebo, thienopyridine derivative, vorapaxar, antithrombocytic agent, lactone, proteinase activated receptor 1, pyridine derivative, Coronary Artery Bypass, Vorapaxar, Cardiovascular diseases [NCEBP 14], Drugs, General Medicine, Middle Aged, Combined Modality Therapy, Cardiovascular diseases, Cardiovascular Diseases, Cardiology, Platelet aggregation inhibitor, Drug Therapy, Combination, Female, Plaquetes sanguínies, Intracranial Hemorrhages, Major bleeding, Medicaments, medicine.drug, medicine.medical_specialty, Acute coronary syndrome, Bypass cardiopulmonary, Hemorrhage, Pharmacotherapy, Blood platelets, Double-Blind Method, Angioplasty, Internal medicine, medicine, Humans, Receptor, PAR-1, Acute Coronary Syndrome, Aged, business.industry, Malalties cardiovasculars, medicine.disease, Surgery, Bypass cardiopulmonar, business, Platelet Aggregation Inhibitors, Follow-Up Studies
Abstract

Item does not contain fulltext BACKGROUND: Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. METHODS: In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS: Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P

Published
2012
Full Text
View/download PDF

6. A rapid computational model for estimating the performance of compliant airfoils in cascades

Author

Sisto, F., Avila, Mathew R., and Naval Postgraduate School (U.S.)

Subjects
ROTOR BLADES(TURBOMACHINERY), Turbomachinery Aeroelasticity
Abstract

We consider the problem of designing the blades in a turbomachine to have a specific schedule of structural stiffness in order to achieve more favorable aerothermodynamic performance characteristics than is possible with rigid blades. The problem of "aerothermodynamic tailoring" is extremely complex because of the need to couple the flow computation over a deforable surface with the structual dynamics computation. In this report an anlysis is presented with accomplishes this objective by means of a two-dimensional incompressible potential flow model using vortex sheet representation of the blades. Details of the analysis and of the resulting computer program together with representative results are described. Naval Postgraduate School, Monterey, CA http://archive.org/details/rapidcomputation00sist National Research Council

Published
1992

10. Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: A new approach for drug delivery

Author

Luisa Pascucci, Eugenio Parati, Lucia Viganò, Giulio Alessandri, Piero Ceccarelli, Maria Ester Bernardo, Gianpietro Bondiolotti, Maurizio Muraca, Silvia Maria Doglia, Augusto Pessina, Arianna Bonomi, Valentina Coccè, Emilio Ciusani, Francesca Sisto, Alberta Locatelli, Diletta Ami, Pascucci, L, Coccè, V, Bonomi, A, Ami, D, Ceccarelli, P, Ciusani, E, Viganò, L, Locatelli, A, Sisto, F, Doglia, S, Parati, E, Bernardo, M, Muraca, M, Alessandri, G, Bondiolotti, G, Pessina, A, Pascucci, L., Cocce, V., Bonomi, A., Ami, D., Ceccarelli, P., Ciusani, E., Vigano, L., Locatelli, A., Sisto, F., Doglia, S. M., Parati, E., Bernardo, M. E., Muraca, M., Alessandri, G., Bondiolotti, G., and Pessina, A.

Subjects
BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Paclitaxel, Mesenchymal stromal cells, Exosome, Microvesicles, Drug delivery, Pharmaceutical Science, FIS/07 - FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA), Antineoplastic Agents, Exosomes, Cell Line, Antineoplastic Agent, chemistry.chemical_compound, Mice, Drug Delivery Systems, Microvesicle, Neoplasms, Cell Line, Tumor, Animals, Humans, Secretion, Tumor microenvironment, Mesenchymal Stromal Cell, Animal, Mesenchymal stem cell, Mesenchymal Stem Cells, In vitro, Cell biology, chemistry, Cell culture, Immunology, Neoplasm, Drug Delivery System, Human
Abstract

Mesenchymal stromal cells (MSCs) have been proposed for delivering anticancer agents because of their ability to home in on tumor microenvironment. We found that MSCs can acquire strong anti-tumor activity after priming with Paclitaxel (PTX) through their capacity to uptake and then release the drug. Because MSCs secrete a high amount of membrane microvesicles (MVs), we here investigated the role of MVs in the releasing mechanism of PTX. The murine SR4987 line was used as MSC model. The release of PTX from SR4987 in the conditioned medium (CM) was checked by HPLC and the anti-tumor activity of both CM and MVs was tested on the human pancreatic cell line CFPAC-1. MVs were isolated by ultracentrifugation, analyzed by transmission (TEM) and scanning electron microscopy (SEM), and the presence of PTX by the Fourier transformed infrared (FTIR) microspectroscopy. SR4987 loaded with PTX (SR4987PTX) secreted a significant amount of PTX and their CM possessed strong anti-proliferative activity on CFPAC-1. At TEM and SEM, SR4987PTX showed an increased number of "vacuole-like" structures and shed a relevant number of MVs, but did not differ from untreated SR4987. However, SR4987PTX-derived-MVs (SR4987PTX-MVs) demonstrated a strong anti proliferative activity on CFPAC-1. FTIR analysis of SR4987PTX-MVs showed the presence of an absorption spectrum in the corresponding regions of the PTX marker, absent in MVs from SR4987. Our work is the first demonstration that MSCs are able to package and deliver active drugs through their MVs, suggesting the possibility of using MSCs as a factory to develop drugs with a higher cell-target specificity. © 2014 Elsevier B.V.

Published
2014

11. Assessment of human herpesvirus-6 infection in mesenchymal stromal cellsex vivoexpanded for clinical use

Author

Arianna Bonomi, Angela Cometa, Maria Ester Bernardo, Loredana Cavicchini, Francesco Locatelli, Francesca Sisto, Augusto Pessina, Valentina Coccè, Maura Ferrari, Pessina, A., Bonomi, A., Cocce, V., Bernardo, M. E., Cometa, A. M., Ferrari, M., Sisto, F., Cavicchini, L., and Locatelli, F.

Subjects
Herpesvirus 6, Human, viruses, medicine.medical_treatment, Blotting, Western, Mesenchymal stromal cells, Roseolovirus Infections, Hematopoietic stem cell transplantation, Biology, Polymerase Chain Reaction, Virus, HHV-6, Membrane Cofactor Protein, Mice, Cell Line, Tumor, medicine, Animals, Humans, Transplantation, Virus receptor, Mesenchymal stem cell, virus diseases, Hematopoietic stem cell, Herpesvirus, Mesenchymal Stem Cells, Fetal Blood, biology.organism_classification, Immunohistochemistry, Infectious Diseases, medicine.anatomical_structure, DNA, Viral, Immunology, Human herpesvirus 6, Bone marrow, Ex vivo
Abstract

Infection or reactivation of human herpesvirus (HHV)-6 represents a potentially serious complication (often involving the central nervous system) in patients receiving either solid organ or hematopoietic stem cell transplantation. The objective of this study was to assess the risk of HHV-6 infectionreactivation in mesenchymal stromal cells (MSCs). MSCs are multipotent cells displaying immunomodulatory properties that have been already successfully used in the clinical setting to enhance hematopoietic stem cell engraftment and to treat steroid-refractory acute graft-versus-host disease. We analyzed 20 samples of ex vivo expanded MSCs, at different passages of culture, isolated both from bone marrow and from umbilical cord blood. Through Western blotting and immunocytochemistry techniques, we investigated the presence of the HHV-6 receptor (CD46) on cell surface, whereas the presence of HHV-6 DNA was evaluated by nested polymerase chain reaction assay. All of the MSC samples tested were positive for the virus receptor (CD46), suggesting their potential susceptibility to HHV-6. However, none of the MSC samples derived from cultures, performed in the perspective of clinical use, was found to harbor HHV-6. This preliminary observation on a consistent number of MSC samples, some of them tested at late in vitro passages, indicates a good safety profile of the product in terms of HHV-6 contamination. Nevertheless, it remains important to set up in vitro experimental models to study MSCs' susceptibility to HHV-6 (and HHV-7) infection, to verify their capacity to integrate the virus into cellular DNA, and to investigate which experimental conditions are able to induce virus reactivation. © 2009 John Wiley & Sons AS.

Published
2009
Full Text
View/download PDF

12. Human skin-derived fibroblasts used as a 'Trojan horse' for drug delivery

Author

A. Vitale, C. A. M. La Porta, Emilio Ciusani, Valentina Coccè, Augusto Pessina, Maura Brambilla, Eugenio Parati, Arianna Bonomi, S. Colombo, Paolo Brambilla, Francesca Sisto, Giulio Alessandri, Coccè, V, Vitale, A, Colombo, S, Bonomi, A, Sisto, F, Ciusani, E, Alessandri, G, Parati, E, Brambilla, P, Brambilla, M, La Porta, C, and Pessina, A

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Stromal cell, Paclitaxel, Dermatology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Drug Delivery Systems, Cell Line, Tumor, medicine, Humans, Anaerobiosis, Cell Proliferation, chemotherapy, mesenchymal stem cells, human stromal dermal fibroblasts, drug delivery, business.industry, Melanoma, Mesenchymal stem cell, Biological activity, Cell cycle, Fibroblasts, medicine.disease, Coculture Techniques, 030104 developmental biology, chemistry, Apoptosis, 030220 oncology & carcinogenesis, Drug delivery, Cancer research, business
Abstract

SummaryBackground Drug toxicity currently represents the main challenge of tumour chemotherapy. Our group recently developed a new method for drug delivery inspired by the ‘Trojan Horse’ concept. Human mesenchymal stem cells (hMSCs) have been shown to play the role of new ‘horses’ in delivering anti-tumour agents, without involving any genetic manipulation. As human stromal dermal fibroblasts (hSDFs) represent an interesting alternative to hMSCs, being easy to isolate, they could be an ideal candidate for this kind of procedure. Aim To investigate whether hSDFs can take up and deliver paclitaxel (PTX) in sufficient concentrations to inhibit a very aggressive melanoma tumour (IgR39) in vitro. Methods hSDFs were primed with high doses of PTX, and then the effect of drug delivery on IgR39 melanoma proliferation in vitro was evaluated using several assays (antiproliferation, transwell cocultures, rosette assays and colony growth assays). Furthermore, the cell cycle and PTX uptake/release mechanism of hSDFs were studied both under both normal and hypoxic conditions. Results hSDFs incorporated PTX and then released it with unaffected pharmacological activity, inhibiting human IgR39 melanoma growth in vitro. The hypoxic conditions did not induce changes in cell cycle pattern and the uptake–release mechanism with PTX was not affected. Conclusions hSDFs can be used as a Trojan horse, as the released drug was functionally active. These results indicated that these cells could be used for clinical treatment as the drug was released into the cellular environment and the primed cells underwent apoptosis.

Published
2015

13. Prevalence of the Internalization-Associated Gene prtF1 in a Bacterial Population of Streptococcus pyogenes Isolated from Children with Acute Pharyngotonsillitis before and after Antibiotic Therapy

Author

A. Lanzafame, Francesco Broccolo, Roberto Mattina, Clementina Cocuzza, Francesca Sisto, Cocuzza, C, Lanzafame, A, Sisto, F, Broccolo, F, and Mattina, R

Subjects
Microbiology (medical), Streptococcus pyogenes, media_common.quotation_subject, education, Immunology, Tonsillitis, Erythromycin, Streptococcus pyogene, Bacterial population, Microbial Sensitivity Tests, Biology, beta-Lactams, medicine.disease_cause, Polymerase Chain Reaction, Microbiology, law.invention, law, Drug Resistance, Multiple, Bacterial, medicine, Humans, Treatment Failure, Adhesins, Bacterial, Child, Internalization, Gene, Polymerase chain reaction, media_common, Pharmacology, Microbial Sensitivity Test, Pharyngitis, medicine.disease, Anti-Bacterial Agents, Pharyngiti, Acute Disease, beta-Lactam, medicine.symptom, Tonsilliti, Human, medicine.drug
Abstract

The prevalence of the internalization-associated prtF1 gene was studied in 837 isolates of Streptococcus pyogenes obtained from 713 pediatric patients presenting with acute pharyngotonsillitis before and after antibiotic therapy. Its association with macrolide resistance and with bacteriological treatment failure was determined. The bacterial population isolated from baseline pharyngeal swabs showed an overall prtF1 positivity rate of 33%. A higher prtF1 positivity was found among erythromycin-resistant strains (45%) showing, however, marked differences between the inducible (iMLS), constitutive (cMLS), and efflux pump (M) resistance phenotypes. The prevalence was statistically higher (p < 0.001) in strains belonging to iMLS (84%) and cMLS (67%) phenotypes as compared to the M phenotype (15%). Interestingly, the prevalence of the prtF1 gene was significantly lower (p = 0.04) in strains belonging to M resistance phenotype as compared to erythromycin-susceptible strains (28%). Failed bacterial eradication was demonstrated in 124 patients. The prtF1 positivity rate remained unchanged in strains isolated before and after therapy in patients treated with macrolides (9/54). On the other hand, the positivity rate for the prtF1 gene was significantly higher (p = 0.015) in strains isolated after therapy with beta-lactams (21/70) as compared to baseline isolates (6/70), indicating a differential selection imposed on the organism by these agents. Finally, a high overall eradication rate (88%) of prtF1-positive isolates, belonging to both the erythromycin-susceptible and -resistant phenotypes, was demonstrated following macrolide treatment

Published
2004
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results