36 results on '"Pospisilova E"'
Search Results
2. Depth-resolved analysis of historical painting model samples by means of laser-induced breakdown spectroscopy and handheld X-ray fluorescence
- Author
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Pospíšilová, E., Novotný, K., Pořízka, P., Hradil, D., Hradilová, J., Kaiser, J., and Kanický, V.
- Published
- 2018
- Full Text
- View/download PDF
3. Structural studies on DCL-1 (CD302), human leukocyte receptor: SW02.S7–100
- Author
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Pospisilova, E., Kavan, D., Chmelik, J., Ruzickova, B., and Novak, P.
- Published
- 2013
4. Correlation of Monocytes, Lymphocytes and Monocyte Ratio (LMR) and Circulating Tumor Cells (CTCs) Presence in Head and Neck Cancer (HNC) Patients during Radiotherapy (RT)
- Author
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Szelachowska, J., primary, Pomiecko-Olszowy, A., additional, Zielecka-Dębska, D.M., additional, Łata-Woźniak, E., additional, Wiśniewska, I., additional, Kulesza, G., additional, Maciejczyk, A., additional, Kolostova, K., additional, Pospisilova, E., additional, Fialova, M., additional, Lichoń, K., additional, Matkowski, R., additional, and Bobek, V., additional
- Published
- 2019
- Full Text
- View/download PDF
5. Circulating tumor cells in renal cancer
- Author
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Klézl, P., primary, Sonsky, J., additional, Grill, R., additional, Pospisilova, E., additional, Kolostova, K., additional, and Bobek, V., additional
- Published
- 2019
- Full Text
- View/download PDF
6. Atmospheric pressure plasma polymerization of organics: effect of the presence and position of double bonds on polymerization mechanisms, plasma stability and coating chemistry
- Author
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Mertens, J., primary, Baneton, J., additional, Ozkan, A., additional, Pospisilova, E., additional, Nysten, B., additional, Delcorte, A., additional, and Reniers, F., additional
- Published
- 2019
- Full Text
- View/download PDF
7. Differences in p53 and Bcl-2 expression in relation to cell proliferation during the development of human embryos
- Author
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Lichnovsky, V, Kolar, Z, Murray, P, Hlobilkova, A, Cernochova, D, Pospisilova, E, Vojtesek, B, and Nenutil, R
- Published
- 1998
8. Ezetimibe added to statin therapy after acute coronary syndromes
- Author
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Cannon, Christopher P., Blazing, Michael A., Giugliano, Robert P., Mccagg, Amy, White, Jennifer A., Theroux, Pierre, Darius, Harald, Lewis, Basil S., Ophuis, Ton Oude, Jukema, J. Wouter, De Ferrari, Gaetano M., Ruzyllo, Witold, De Lucca, Paul, Kyungah, Im, Bohula, Erin A., Reist, Craig, Wiviott, Stephen D., Tershakovec, Andrew M., Musliner, Thomas A., Braunwald, Eugene, Califf, Musliner T, Robert M., Tershakovec, A, Gurfinkel, E, Aylward, P, Tonkin, A, Maurer, G, Van de Werf, F, Nicolau, Jc, Theroux, P, Genest, J, Armstrong, P, Corbalan, R, Isaza, D, Spinar, J, Grande, P, Voitk, J, Kesaniemi, A, Bassand, Jp, Farnier, M, Darius, H, Keltai, M, Mathur, A, Mittal, S, Reddy, K, Lewis, B, De Ferrari GM, Ophuis, To, Jukema, J, White, H, Pedersen, T, Britto, F, Ruzyllo, W, Carrageta, M, Duris, T, Dalby, A, Seung, Kb, Lopez-Sendon, J, Dellborg, M, Mach, F, Guneri, S, Parkhomenko, A, Brady, A, Cannon, C, Blazing, M, Ballantyne, C, de Lemos, J, Kleiman, N, Mcguire, Dk, Centeno, E, Casalins, M, Cartasegna, L, Beltrano, Mc, Guerrero, R, Fanuele, M, Berra, F, Egido, J, Colombo, H, Dellatorre, M, Terns, P, Blumberg, E, Reges, P, Azize, G, Ramos, H, Fernandez, R, Carlessi, C, Milesi, R, Schmuck, R, Duronto, E, Procopio, G, Carlevaro, O, Maffeo, H, Beloscar, J, Viso, M, Hominal, M, Castoldi, M, Bluguermann, J, Mauro, D, Macin, S, Cocco, N, Ruiz, N, Ricart, J, Lozada, A, Nani, S, Turri, D, Fernandez, H, Caruso, O, Zarandon, R, Bono, J, Arias, V, Allall, O, Marino, J, Cusimano, S, Schygiel, P, Buzetti, C, Penaloza, N, Berli, M, Worthley, S, Roach, A, Chew, D, Wright, T, Leitch, J, Hicks, E, Rankin, J, Venn-Edmonds, C, Lehman, R, Morrison, H, Shaw, J, Mak, V, Hii, C, Smith, K, Cross, D, Lilwall, L, Nelson, G, Loxton, A, Horowitz, J, Rose, J, Steinwender, C, Leisch, F, Kammler, J, Brussee, H, Zweiker, R, Niederl, E, Weihs, W, Giorgio, G, Lang, I, Drexel, H, Zanolin, D, Hoppe, U, Atzenhofer-Baumgartner, K, Pichler, M, Hainzer, D, Eber, B, Pichler, F, Foeger, B, Wechselberger, T, Mayr, H, Hofer, J, Stockenhuber, F, Warlits, B, Huber, K, Egger, F, Weidinger, F, Ziegler, B, Jirak, P, Metzler, B, Pachinger, O, Wanitschek, M, Auer, J, Grabscheit, G, Podczeck-Schweighofer, A, Priesnitz, T, Frank, H, El Allaf, D, Marechal, P, Roosen, J, Joly, E, Lefebvre, P, Arend, C, Sinnaeve, P, De Velder, L, Hellemans, S, Vanhauwaert, B, Van Dorpe, A, Heyse, A, Vantomme, C, Striekwold, H, Van Den Broeck, D, Lancellotti, P, Schoors, D, Lemoine, I, Taeymans, Y, De Wolf, L, Brike, C, Vercauteren, S, Tahon, S, Vervoort, G, Mestdagh, I, Pirenne, B, Cardinal, F, Lips, S, Dujardin, K, Debrouwer, K, Dhooghe, G, Holvoet, G, van de Borne, P, Renard, M, De Clippel, M, Lesseliers, H, Van Miert, N, Saraiva, J, Vicente, C, Rossi, P, Dos Santos LB, Duda, N, Tognon, Ap, Serrano, C, Gomes, Fl, Manenti, Er, Silveira, Ds, Maia, L, Mouco, Om, Paiva, M, Antonangelo, A, de Souza, J, Lino, Ea, Leães, P, Blacher, Mg, Kormann, A, Ultramari, Ft, Dutra, O, Mendelski, Am, Morgado, S, Ardito, W, Greque, G, Ardito, Rv, Pimentel Filho, P, Zucchetti, C, Alves, A, Seabra, Am, Mattos, M, Miranda, Lf, Silva, D, Uehara, Rm, Marin Neto, J, Schmidt, A, Braga, J, Rodrigues, A, Abrantes, J, Pinheiro, L, Bodanese, L, Magedanz, Éh, Piegas, L, Dos Santos ES, Wainstein, M, Ribeiro, J, Stein, R, Marino, R, Machado, Vm, Moraes Junior, J, Guimarães, S, da Costa FA, Ferraz, Rf, Albuquerque, D, Rocha, Rm, de Carvalho Moreira, R, Dohmann, H, Costantini, C, Tarastchuk, Jc, Coelho, O, Cirillo, W, Sousa, A, Almeira, As, Stefanini, E, Silva, F, Teixeira, M, da Cunha, C, Précoma, D, Facchi, Tl, Rupka, D, Thiessen, S, Warnica, J, Smith, B, Della Siega, A, Klinke, P, Nelson, S, Dion, D, Gilbert, N, Hui, W, Kvill, L, Sussex, B, Luther, A, Dupuis, R, Ouimet, F, Pandey, A, Clarus, S, Senaratne, M, Ferdinandis, H, Mukherjee, A, Bozek, B, Vizel, S, Markov, G, Zimmermann, R, Stephens, W, Tremblay, B, Wong, G, Uchida, N, Brossoit, R, Peck, C, Van Kieu, C, Forgione, M, Bata, I, Cossett, J, Kostuk, W, Arnold, M, Bone, C, Grondin, F, Bilodeau, N, Gosselin, G, David, M, Giannoccaro, J, Beresford, P, Polasek, P, Roberts, P, Doucet, M, Beaudry, M, Cheung, S, Cleveland, T, Bhargava, R, Mccallum, A, Ma, P, Morrissette, J, Cleveland, D, Chadwyn, D, Nigro, F, Weeks, A, Cryderman, C, Leader, R, Houde, G, Rousseau, S, Pearce, M, Radyk, M, Lonn, E, Magi, A, Lefkowitz, C, Sandrin, F, Coffin, N, Lubelsky, B, Coldwell, J, Habot, J, Mcpherson, C, De Larochelliere, R, Roy, M, Haichin, R, Barber, C, Bhesania, T, Kitagawa, H, To, T, Donnelly, B, Tymchak, W, Harris, L, Kouz, S, Huynh, T, St Jacques, B, Lamy, A, Rizzo, A, Stein, J, Childs, C, Wong, B, Poirier, R, Gupta, M, Dela Cruz, C, Constance, C, Gauthier, M, Ervin, F, Ouellette, M, Kokis, A, Lemay, C, Kwok, K, Leung, C, Lee, D, Nesmith, J, Renton, J, Syan, G, Turek, M, Hogan, D, Griffin, P, Lipson, A, Winestock, J, Abramson, B, Fogel, A, Gagne, C, Bergeron, J, Clarke, A, Slipp, S, Darcel, I, Carling-Chambers, L, Kannampuzha, P, Pallie, S, Krekorian, S, Vertes, G, Roth, S, Lai, K, Heath, J, Perez, L, Arriagada, G, Castro, P, Villa, F, Rodríguez, M, Ramos, G, Baraona, F, Núñez, A, García, M, Jofre, C, Silva, P, Lamich, R, Yovaniniz, P, Escobar, E, Dussaubat, A, Segura, E, Ramirez, M, Lapostol, C, Palma, A, Encina, L, Zapata, M, Baeza, N, Varela, P, Pérez, L, Jaramillo, C, Ruiz, S, Sanchez, G, Perdomo, I, Manzur, F, Cohen, Le, Velasquez, J, Arana, C, Alvarez, Y, Triana, M, Balaguera, J, de Salazar, D, Rendon, N, Botero, R, Ruiz, A, Saaibi, J, Medina, J, Jaramillo, M, Calderón, Mj, Delgado, J, Bohorquez, R, Medina, Mf, Herrera, M, Rosales, D, Mendoza, F, Martinez, S, Ternera, A, Castro, R, Baiz, A, Martinez, M, Orozco, A, Suarez, M, Fonseca, Y, Beltran, R, Cepeda, M, Jaramillo, N, Valenzuela, C, Gutierrez, M, Sanchez, A, Vitovec, J, Hlinomaz, O, Poloczek, M, Mayer, O, Veselka, J, Vejvoda, J, Soucek, M, Spac, J, Novobilsky, K, Srp, V, Francek, L, Branny, M, Sknouril, L, Motovska, Z, Rohac, F, Stankova, A, Fiala, T, Holub, M, Zeman, K, Pohludkova, L, Pospisilova, E, Tuma, P, Cihalik, C, Oral, I, Podpera, I, Stepanovova, R, Uricar, M, Solar, M, Pelouch, R, Porzer, M, Grussmannova, K, Stipal, R, Reichert, P, Hradec, J, Kral, J, Sejkova, B, Janek, B, Pitha, J, Linhart, A, Polacek, P, Koeber, L, Clemmensen, P, Hebin, Ch, Schmidt, E, Pedersen, Ms, Roseva-Nielsen, N, Kristensen, K, Bang-Hansen, T, Jensen, J, Laage-Petersen, J, Nielsen, H, Stokholm, E, Thayssen, P, Cappelen, H, Jensen, T, Winther-Friis, B, Klausen, I, Hedegaard, B, May, O, Andersen, M, Bottzauw, J, Lush, A, Markenvard, J, Vestager, Km, Bronnum-Schou, J, Hempel, H, Petersen, J, Nielsen, Aj, Thomsen, K, Nielsen, T, Nygaard, A, Sykulski, R, Jensen, Bs, Ralfkiaer, N, Gottschalck, H, Rasmussen, S, Pedersen, Lr, Dodt, K, Skovsbøl, M, Andersen, O, Tuxen, C, Meier, Aw, Kristensen, T, Rasmussen, O, Lopez, J, Salazar, D, Sanchez, L, Rosero, F, Penaherrera, E, Duarte, Yc, Marmol, R, Andrade, G, Guzman, E, Morillo, A, Aug, L, Loogna, I, Laanmets, P, Mustonen, J, Mäntylä, P, Kesäniemi, A, Ukkola, O, Kervinen, H, Juhela, S, Juvonen, J, Toppinen, A, Jarvenpaa, J, Syvanne, M, Svahn, T, Voutilainen, S, Huotari, A, Nikkila, M, Raiskinmäki, S, Kotila, M, Rajala, A, Laukkanen, J, Hiltunen, P, Melin, J, Nyman, K, Luukkonen, J, Kosonen, P, Huttunen, M, Seppänen, V, Airaksinen, J, Juonala, M, Lehto, S, Savolainen, K, Halkosaari, M, Sia, J, Palomaki, A, Luoma, J, Utriainen, S, Valpas, S, Tiensuu, T, Lilleberg, J, Kainulainen, R, Schiele, F, Bassand, J, Meneveau, N, Galinier, M, Jean, M, Martelet, M, Mouallem, J, Elbaz, M, Puel, J, Carrié, D, Coisne, D, Varroud-Vial, N, Jaboureck, O, Dujardin, J, Leroy, F, Mansourati, J, Funck, F, Jourdain, P, Guillard, N, Coviaux, F, Gay, A, Dourmap-Collas, C, Froger-Bompas, C, Paillard, F, Tricot, O, Maquin-Mavier, I, Dubois-Rande, Jl, Pongas, D, Paris, Ap, Delahaye, F, Ovize, M, Benyahya, L, Bonnet, J, Belle, L, Mangin, L, Lafitte, B, Zemour, G, Doux, N, Agraou, B, El Mansour, N, Traisnel, G, El Jarroudi, M, Ohlmann, P, Diadema, B, Escande, M, Legros, G, Demarcq, Jm, Haftel, Y, Alsagheer, S, Dambrine, P, Cottin, Y, Ghostine, S, Caussin, C, Gacem, A, Bouvier, Jm, Poulard, J, Davy, J, Furber, A, Prunier, F, Muenzel, T, Genth-Zotz, S, Appel, K, Kretzschmar, D, Ferrari, M, Terres, W, Uher, T, Schulze, H, Ochs, H, Morbach, S, Duengen, H, Gross, M, Oezcelik, C, Tahirovic, E, Heuer, H, Laschewski, B, Kadel, C, Rahn, G, Steiner, S, Kreuzer, J, Tsoy, I, Zeiher, A, Muegge, A, Hanefeld, C, Boehm, S, Boudriot, E, Hodenberg, E, Lippe, B, Hausdorf, C, Sydow, K, Baldus, S, Schlesner, C, Tiroch, K, Haltern, G, Guelker, H, Wilhelm, J, Dietz, S, Ebelt, H, Buerke, M, Rupprecht, H, Rittgen, J, Schaeufele, T, Meinhardt, G, Schieber, M, Honold, M, Sieprath, S, Nienaber, C, Hacker, J, Butter, C, Lapp, H, Hirn, S, Pauschinger, M, Zahn, R, Scheffler, U, Schaefer, A, Schieffer, B, Tebbe, U, Kriete, M, Mudra, H, Raeder, T, Braun, P, Zeymer, U, Kouraki, K, Reppel, M, Schunkert, H, Weil, J, Olbrich, H, Schwaiger, P, Mueller, O, Blessing, E, Buss, I, Bohlscheid, V, Kaddatz, J, Skowasch, D, Nickenig, G, Twelker, K, Osterhues, H, Varghese, T, Burghard, S, Kaeaeb, S, Klauss, V, Sohn, Hy, Hauptmann, K, Schulze, M, Gall, K, Felix, S, Doerr, M, Mante, J, Gulba, D, Freick, M, Werner, G, Kleinertz, K, Hobbach, Hp, Halbach, M, Mueller-Ehmsen, J, Mueller, Me, Mitrovic, V, Peil, A, Laufs, U, vom Dahl, J, Baumanns, S, Scholtz, W, Wiemer, M, Haude, M, Van de Loo, A, Pistorius, K, Schaefer, J, Schwinger, R, Goeing, O, Jung, W, Birkemeyer, R, Lee, W, Kong, S, Yu, C, Chui, K, Merkely, B, Szelényi, Z, Polgár, P, Svab, S, Herczeg, B, Bajcsi, É, Vértes, A, Davidovits, S, Nagy, A, Király, C, Lupkovics, G, Kenéz, A, Poór, F, Takács, J, Kirschner, R, Simonyi, G, Koncz, J, Édes, I, Gergely, S, Katona, A, Nagy, E, Kovács, Z, Gyetvai, I, Salamon, C, Kolman, É, Sitkei, É, Csapó, K, Molnar, K, Mező, I, Sereg, M, Reddy, P, Manjunath, C, Narayanappa, S, Kumar, S, Sinha, N, Kapoor, A, Christopher, J, Reddy, G, Rani, M, Oomman, A, Ramamurthee, K, Kumar, N, Pasha, Ss, Rao, C, Murty, Gs, Chopra, A, Kapila, D, Bali, H, Chattree, K, Hasan, O, Suryaprakash, G, Rao, D, Babu, R, Bhargavi, M, Naik, S, Khan, S, Chopra, V, Sapra, R, Kaul, U, Ghose, T, Menon, R, Battikadi, S, Mullasari, A, Subban, Vk, Dani, S, Iby, M, Chandra, P, Sethi, S, Bhargava, M, Arora, P, Tyagi, G, Padmanabhan, T, Malhotra, S, Talwar, K, Shafiq, N, Kasliwal, R, Bansal, M, Eldar, M, Berger, M, Shechter, M, Atar, S, Roguin, N, Kilimnik, M, Hayek, T, Hamoud, S, Katz, A, Plaev, T, Shotan, A, Vazan, A, Weiss, A, Leibowitz, D, Zimlichman, R, Ben-Aharon, J, Hammerman, H, Dragu, R, Rozenman, Y, Witzling, V, Tzivoni, D, Moriel, M, Halkin, A, Sheps, D, Bogomolny, N, Mosseri, M, Khudyak, Y, Halabi, S, Uziel-Iunger, K, Yuval, R, Shimoni, S, Caspi, A, Botwin, S, Gavish, D, Sandler, A, Pollak, A, Kreisberg, B, Hussein, O, Jabal, K, Henkin, Y, Grosbard, A, Rosenschein, U, Rivlin, E, Zeltser, D, Platner, N, Porter, A, Harel, N, Lishner, M, Elis, A, Karny, M, Fuchs, S, Stein, G, Grossman, E, Gealel, Z, Schlaeffer, F, Liberty, I, Golik, A, Tzuman, O, De Ferrari, G, Pavesi, C, Poggio, L, Damiano, S, Pazzano, As, Mennuni, M, Paloscia, L, Mascellanti, M, Piovaccari, G, Grosseto, D, Mascia, F, Vetrano, A, Zingarelli, A, Mazzantini, S, Visconti, L, Terzi, G, Senni, M, Gavazzi, A, Scuri, P, Carmelo, M, De Caterina, R, Conti, M, Novo, S, Graceffa, A, Arvigo, L, Lunetta, M, Filardi, P, Chiariello, M, Scala, O, Pirozzi, E, Musella, F, Moretti, L, Testa, M, Vicentini, A, De Feo, S, Biasucci, L, Cardillo, Mt, Puccioni, E, Galli, M, Menegato, A, Margheri, M, Maresta, A, Gatti, C, Guarini, P, Damiano, M, Golino, P, Porcu, M, Fele, N, Gensini, G, Lombardi, A, Ciuti, G, Bernardi, D, Mariani, P, Paolini, E, Marenzi, G, Moltrasio, M, Terrosu, P, Chessa, P, Guglielmino, G, Miccoli, F, Oldoino, E, Ragni, M, Poli, M, Basso, V, Rapezzi, C, Branzi, A, Gallelli, I, Perna, G, Guazzarotti, F, Marra, S, Usmiani, T, Olivari, Z, Calzolari, D, Santoro, G, Minneci, C, Achilli, A, Nassiacos, D, Sommariva, L, Romeo, F, Fedele, Francesco, Mancone, Massimo, Foschi, Ml, Bruno, N, Centurion, C, Patrizi, G, De Maria, E, Gonnelli, S, Vichi, V, Cassadonte, F, Rotella, G, Capucci, A, Villani, G, Gaspardone, A, Ferrante, R, Scollo, V, Pancaldi, L, Saccà, S, Gabrielli, D, Ciliberti, D, Savini, E, Binaghi, G, Di Biase, M, Ieva, R, Fattore, L, Cicia, G, Cavallini, C, Tamburino, C, Sacco, A, Mafrici, A, Di Pasquale, G, Pavesi, Pc, Scioli, R, Lioy, E, Occhiuzzi, E, Matino, Mg, Russo, V, Moscogiuri, Mg, Cuccia, C, Forgione, C, Volpe, M, Palano, F, Branca, G, Rossi, R, Modena, M, Olaru, Ia, Zanini, R, Cianflone, D, Cristell, N, Pantaleoni, M, Guiducci, U, Menozzi, C, Gaddi, O, Fasulo, A, Indolfi, C, Emanuele, V, Guerra, F, Iliceto, S, Marotta, C, Morocutti, G, Presbitero, P, Rossi, M, Bonatti, S, Grieco, A, Chiodi, L, Betti, I, Zuppiroli, A, Fanelli, R, Stanco, G, Azzolini, P, Ruggieri, C, Bocconcelli, P, Airoldi, F, Tavano, D, Brunelli, C, Caso, P, Scalzone, A, Ghigliotti, G, Facciorusso, A, Sim, K, Kiam, O, Chee, K, Bin Ismail, O, Zambahari, R, Ophuis, T, van Nes, E, Werter, Cj, Ophuis, Aj, Troquay, Rp, Hamer, Bj, Lenderink, T, Feld, Rj, van Hessen MW, Viergever, Ep, van der Sluis, A, Lok, Dj, Badings, Ea, Nierop, Pr, Danse, Iy, Hermans, Wr, Holwerda, Nj, Thijssen, Hj, Theunissen, Lj, van der Zwaan, C, Van Den Berg BJ, Hendriks, Ih, Ronner, E, Withagen, Aj, Dijkshoorn-Giesen, Ah, Ezechiels, Jp, Kuijper, Af, Den Hartog FR, Van Kalmthout PM, Buijs, Em, van der Zeijst, M, Zwart, Pa, Zuidgeest, Ja, van Eck, M, Daniels, Mc, van der Ven-Elzebroek, N, Van 't Hof, A, van Boven AJ, van der Weerdt, A, Dunselman, Ph, Alings, Ma, van Es RF, The, Sh, Gurlek, C, Liem, Ah, van Lennep HW, Van Vlies, B, Kalkman, C, Swart, Hp, van der Bij, P, Taverne, R, Ciampricotti, R, van Dam, C, Spierenburg, H, van Ruijven, I, van Kempen LH, Willems, Ff, Dirkali, A, Stoel, I, Plomp, J, Veldmeijer, S, Tjeerdsma, G, Nijmeijer, R, Van Hal JM, Bartels, Gl, Posma, Jl, Linssen, Gc, Fauser, Cg, Waalewijn, Ra, Groenemeijer, Be, Pos, L, Fast, Jh, Droste, Ht, Westenburg, J, Veenstra, W, Koolen, J, van Loo LW, Smits, W, Milhous, Jg, van Rossum, P, 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Sabatine, M., Marti, J., Perlman, R., Pavlides, A., Joffe, I., Albirini, A., Campbell, T., Puri, S., Lopez, C., Pearce, D., Shah, D., McPherson, J., Donegan, R., Murdock, D., Block, D., Malik, A., Musina, R., Dauber, I., Varner, C., Bach, R., Palazzolo, M., Bhalla, H., Thompson, M., Pollock, S., Johnson, S., Lipson, L., Brunk, S., Karas, S., Vicari, R., Kuvin, J., Mooney, P., Aycock, G., Lane, B., Sharma, M., Gibson, T., Chang, G., DiVito, P., Mehta, R., Watkins, K., Chiu, A., Gunderson, J., Tedder, B., Williams, P., Hage-Korban, E., Childs, A., Banerjee, S., Kazi, F., Bennett, J., Barnes, D., Wohns, D., Noorman, C., Aggarwal, K., Lau-Sickman, A., Paulowski, J., Amos, M., Rider, J., Fenton, S., Schantz, M., Hakas, J., Mcsorley, J., Felten, W., Bitzer, V., Russell, J., Loyo, J., Adjei, A., Mehta, K., Uretsky, B., Hale, M., Shaikh, S., Miller, M., Hollenbaugh, D., Crawford, K., Fortuin, D., Galindo, A., Del Core, M., Butkus, E., Collins, J., Prior, J., Hahn, R., Greene-Nashold, J., 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E., Cullen, T., Eisenberg, S., Chronos, N., Allen, R.P., Erickson, B., Mahon, K., Kirby, A., Siegel, C., Stroud, L., Johnson, J., Panchal, V., Pearson, A., Abell, T., De Gregorio, M., Boomer, L., Vahdat, O., VanNatta, B., Long, P., Chalavarya, G., Skatrud, L., Carey, C., Wright, W., Mechem, C., Matthews, B., Adams, A., Vora, K., Wead, J., Koren, M., Gregory, D., El Khadra, M., Peacock, G., Kieval, J., Barron, M., Lewis, D., Grice, R., Bobek, M., Moore, C., Nygaard, T., Fischell, T., Salman, W., Schneider, C., Muhlestein, B., Peeler, D., Chang, D., Todd, A., Chilakamarri, V., Hanley, P., Gelormini, J., Iacona, M.A., Effron, B., Mazzurco, S., Mazzella, M., Wyman, P., Orchard, R., Battin, D., Rezkalla, S., Bishop, C., Sharp, S., Gredler, F., Knap, P., Fadel, M., Saucedo, J., Keng, A., Imburgia, M., Blank, E., Effat, M., Khoury, S., Mardis, R., Baldari, D., Tafuri, L., Mascolo, R., Taylor, D., Mandviwala, M., Khan, W., Mumford, T., Mayer, N., Mitchell, B., Oliver, T., Lombardi, W., Zimmerman, T., Rohrbeck, S., Cooke, L., Craig, M., Mego, D., Griffin, B., Perez, J., LeClerc, K., Addington, J., Aboufakher, R., Ahmed, A., Westecott, B., Steel, K., Hawkins, K., Shah, A., Ward, U., McGreevy, M., Goldberg, R., Prashad, R., McDonough, C., Silver, K., Josephson, R., Witsaman, S., Labib, S., Woodhead, G., Schrank, J., Bell, K., Chandna, H., Holly, D., Bethea, C., Fife, B., Gruberg, L., Singer, A., Ramgadoo, M., Lalonde, T., Morin, R., French, W., Barillas, O., Gradner, G., Kahn, Z., Gress, J., Rocco, D., Thew, S., Stifter, W., Fisher, M., McNamara, J., Kupfer, J., Agocha, A., Cush, S., Jones, S., Whitaker, T., Stover, T., Kumkumian, G., Kent, K., Greenberg, A., Pandey, P., Pytlewski, G., Matsumura, M., Kai, W., Sameshima, S., Thomas, J., MacNicholas, D., Pillai, K., Jones, D., Navas, J.P., Laskoe, B., Patel, P., Fini, G., Minor, S., Shipwash, T., Cabrera-Santamaria, A., Rivera, E., Mincher, L., Jafar, M., Yen, M., Finkle, C., Rahimtoola, A., Severson, L., Labroo, A., Jinich, D., Tam, K., Vogel, C., Aggarwal, R., Zakhary, B., Curtis, S., Lyster, M., Humphrey, K., Lavine, P., Fujise, K., Birnbaum, Y., Allen, J., Kesselbrenner, M., Michel, K., Staniloae, C., Liu, M., Sonel, A., Macioce-Caffas, A., Amidon, T., Leggett, J., Yedinak, S., Gudmundsson, G., Sabharwal, J., Dagefoerde, N., Wu, W., Meyerrose, G., Roongsritong, C., Jenkins, L., Lieberman, S., Sokol, S., Gutierrez, C., Nelson, C., Barrett, J., Hotchkiss, D., Farley, A., Atassi, K., Christy, L., Baig, M., Di Fazio, J., Meengs, M., Thomas, K., Surmitis, J., DeVault, S., Farhat, N., Hulyalkar, A., Riddell, L., Rivera, W., Sheynberg, B., Kobayashi, J., Katsaropoulos, J., Jan, M., Krucoff, M., Paterno, C., Chandrasekaran, S., Curry, R., Cassavar, D., Wheeler, M., McGarvey, J., Schwarz, L., Miller, E., Andrea, B., Carswell, B.S., Lurie, M., Patti, J., Bowden, W., Vasiliauskas, T., Latham, R., Schwartz, B., Bradford, L., Mattleman, S., Wertheimer, J., Goulden, D., Khan, M., Hawkins, B., Ostfeld, R., Mueller, H., Ash, Y., Wilson, V., Bayer, M., Marshall, J., Dobies, D., Dawson, G., Osman, A., Saba, F., Costello, T., Fuentes, F., Underwood, C., Vijay, N., Washam, M., Dietz, W., Glasgow, B., Mukherjee, S., Hinchion, N., Speirs, S., Thornley, A., Lee, K., Movahed, M., Strootman, D., Chernick, R., Parrott, C., Flock, C., Marques, V., Syzmanski, E., Rama, P., Domingo, D., Wu, L., Bauer, B., Dionisopoulos, P., Aggarwal, A., Holcomb, R., Foster, R., Hancock, T., Hargrove, J., Fletcher, A., Stine, R., Bullivant, M., Adams, K., Lohman, J., Klepper, V., Kabour, A., Neidhardt, J., Phillips, W., Tardiff, S., Aji, J., Corut, S., Foster, G., Firek, C., St Goar, F., Sumner, R., Davis, T., Schneider, R., Schneider, W., Villa, A., Desai, V., Chhabra, A., Banks, K., Herzog, W., Burley, T., Quyyumi, A., Smiley, W., Manocha, P., Fishbein, G., Weller, C., Coffman, A., Kim, C., Kedia, A., Firth, B., Rizvi, M., Dahiya, R., Foster, B., Balcells, E., Metzger, D.C., Lester, J., Bissett, J., Fahdi, I., Sides, E.A., Azrin, M., Martin, C., Quick, A., Conaway, D., Garg, M., Schallert, G., Lancaster, L., Mckissick, S., Atieh, M., Garbarino, J., Eisenberg, D., Uusinarkaus, K., Wirtemburg, P., Ellis, J., Cristaldi, J., Berglund, R., Negus, B., Pappas, J., Rocha, R., Nguyen, T., Stone, J., Janosik, D., Labovitz, A., Elmore, N., Dave, R., Loffredo, K., Gabriel, G., Snyder, C., Ahmed, O., Stone, H., Kelley, M., Diffenback, M., Friedman, B., Zirkle, J., Severa, L., Sample, S., Dignen, K., Raisinghani, A., Ben-Yehuda, O., Ghannadian, B., Moscoso, R., Mankowski, J., Boliek, W., Rukavina, M., Davis, W., Ledbetter, S., Handel, F., Mastouri, R., Mahenthiran, J., Foltz, J., Malhotra, V., Jonas, J., Berk, M., Singh, V., Nelson, M., Elsner, G., Gall, J., Kondo, N., Frank, S., Chandraratna, P., Ranasinghe, S., Ebrahimi, R., Treadwell, M., Walters, B., Hughes, L., Kramer, J., Kumar, K., Mente, T., Lachterman, B., Schifferdecker, B., Munshi, K., Sease, D., Waldo, D., Chandler, G., Manns, D., Nahhas, A., Kamalesh, M., Williams, V., Reich, D., Desalca, M., Sharma, S., Liston, M., Gupta, K., Costa, M., Altschuller, A., Lemmertz, K., Shanes, J., Hansen, C., Therrien, M., Mendelson, R., Ramnarine, R., Myers, G., Donovan, C., Klein, M., Fine, D., Owens, S., Murray, C., Ketroser, R., Heifetz, S., Darnell, Z., Touchon, R., Taghizadeh, B., Bohle, D., Norwood, D., Forrest, T., Jackson, S., Shumate, K., Bayles, A., Masroor, M., North, W.K., Fishberg, R., Merveil-Ceneus, B., Butcher, R., Menapace, F., Kilbride, S., Ramabadran, R.S., Loukinen, K., Khalil, J., Ramabadran, R., Walsh, S., Gill, S., Cyncar, R., McLachlan, J., Surakanti, V., Rusterholtz, L., Shoukfeh, F., Stephenson, L., Tsang, M., Nolan, V., Gilchrist, I., Jefferson, D., Feldman, T., Reyes, L., Santos, R., Little, W., Wesley, D., Gharib, W., Mendell, A., Esham, G., Kakavas, P., Whitcomb, C., Book, K., Bazzi, A., Alvarez, J., Cohen, Y., Ayres, T., Rhule, V., Labib, A., Schuler, P., Zughaib, M., Telck, K., Bikkina, M., Turnbull, K., Sharma, T., Orosz, S., Shah, R., Petrino, M., Hughes, M., Hershey, J., Hudock, D., Hui, P., Von Bakonyi, A., Arnold, A., Kappel, D., Pennock, G., Cloud, B., Tucker, K., Harp, L., Hoover, C., Eisenhauer, M., Roth, J., Young, C., Thai, H., Escalante, A., Bautista, J., Gazmuri, R., Nyland, J., Cubeddu, L., DeFranco, A., Dias, D., Fielding, M., Reeves, R., Hermany, P., Meissner-Dengler, S., Evans, M., Flores, E., Tannenbaum, A., McGarr, K., Moran, J., Stout, E., Allred, S., Henderson, D., Crandall, L., Strote, J., Voyles, W., Robeson, D., Bedoya, R., Omar, B., Pettyjohn, F., Revere, C., Coy, K., Margolis, J., Sotolongo, C., Scheffel, M., Munir, A., Shirwany, A., Douglas, L., Girala, R., Humphreys, R., Agarwal, J., Bankowski, D., Watson, R., Bishop, B., Klementowicz, P., Blais, D., Cohen, B., Lobur, E., Dimenna, J., Dempsey, K., Izzo, M., Bondi, L., Carell, E., Eaton, C., Saltiel, F., Grewal, G., Connolly, T., Little, T., Wiegman, P., Gips, S., Held, J., Paraschos, A., Quesada, R., Goudreau, E., Sears, M., Istfan, P., Holt, S., McClung, J., Nguyen, N., Quintana, O., Gottlieb, D., Knutson, T., Barringhaus, K., Lester, F., Sullivan, P., Rodriguez-Ospina, L., Cannon, Cp, Blazing, Ma, Giugliano, Rp, Mccagg, A, White, Ja, Theroux, P, Darius, H, Lewis, B, Ophuis, To, Jukema, Jw, De Ferrari, Gm, Ruzyllo, W, De Lucca, P, Im, K, Bohula, Ea, Reist, C, Wiviott, Sd, Tershakovec, Am, Musliner, Ta, Braunwald, E, Califf, Rm, for the IMPROVE-IT, Investigator, Cianflone, D, Cardiovascular Division (SZG), Brigham and Women's Hospital [Boston], College of Information Science and Engineering, Ritsumeikan University, Montreal Heart Institute (MONTREAL HEART INSTITUTE), Laboratoire des Micro-algues toxiques, Institut Louis Malardé [Papeete] (ILM), Institut de Recherche pour le Développement (IRD)-Institut de Recherche pour le Développement (IRD), Interuniversity Cardiology Institute Netherlands, Institute of Cardiology (WARSAW - Cardiology), Institute of Cardiology, Merck Sharp & Dohme Corp., Merck & Co. Inc, DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, Facolta' di MEDICINA e CHIRURGIA, AREA MIN. 06 - Scienze mediche, Cannon, C.P., Blazing, M.A., Giugliano, R.P., Mccagg, A., White, J.A., Lewis, B.S., Jukema, J.W., De Lucca, P., Im, K., Bohula, E.A., Reist, C., Wiviott, S.D., Tershakovec, A.M., Musliner, T.A., Braunwald, E., Califf, R.M., for the IMPROVE-IT Investigators [.., C. Rapezzi, ], Other departments, Cannon, Christopher P, Blazing, Michael A., Giugliano, Robert P., Mccagg, Amy, White, Jennifer A., Theroux, Pierre, Darius, Harald, Lewis, Basil S., Ophuis, Ton Oude, Jukema, J. Wouter, De Ferrari, Gaetano M., Ruzyllo, Witold, De Lucca, Paul, Kyungah, Im, Bohula, Erin A., Reist, Craig, Wiviott, Stephen D., Tershakovec, Andrew M., Musliner, Thomas A., Braunwald, Eugene, and Califf, Robert M.
- Subjects
Male ,Simvastatin ,acute coronary syndrome ,aged ,anticholesteremic agents ,azetidines ,cardiovascular diseases ,cholesterol, ldl ,double-blind method ,drug therapy, combination ,ezetimibe ,female ,humans ,hydroxymethylglutaryl-coa reductase inhibitors ,kaplan-meier estimate ,male ,middle aged ,simvastatin ,triglycerides ,medicine (all ,[SDV]Life Sciences [q-bio] ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Bococizumab ,Triglyceride ,chemistry.chemical_compound ,0302 clinical medicine ,Azetidine ,Cardiovascular Disease ,Anticholesteremic Agent ,Acute Coronary Syndrome ,Aged ,Anticholesteremic Agents ,Azetidines ,Cardiovascular Diseases ,Cholesterol, LDL ,Double-Blind Method ,Drug Therapy, Combination ,Female ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Middle Aged ,Triglycerides ,030212 general & internal medicine ,Medicine (all) ,Research Support, Non-U.S. Gov't ,Hazard ratio ,General Medicine ,Acute Coronary Syndrome, Aged ,Anticholesteremic Agents, Azetidines, Cardiovascular Diseases ,Ezetimibe, Female, Humans ,Male, Middle Aged ,3. Good health ,Multicenter Study ,Editorial ,Cholesterol ,Randomized Controlled Trial ,Combination ,Ezetimibe ,lipids (amino acids, peptides, and proteins) ,Human ,medicine.drug ,medicine.medical_specialty ,Acute Coronary Syndroms ,Urology ,Acute Coronary Syndrome/drug therapy ,Anticholesteremic Agents/adverse effects ,Anticholesteremic Agents/therapeutic use ,Azetidines/adverse effects ,Azetidines/therapeutic use ,Cardiovascular Diseases/epidemiology ,Cardiovascular Diseases/mortality ,Cardiovascular Diseases/prevention & control ,Cholesterol, LDL/blood ,Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ,Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ,Simvastatin/therapeutic use ,Triglycerides/blood ,NO ,LDL ,03 medical and health sciences ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Drug Therapy ,Internal medicine ,Journal Article ,medicine ,Comparative Study ,Alirocumab ,business.industry ,PCSK9 ,ta3121 ,Lomitapide ,DOENÇAS CARDIOVASCULARES ,Endocrinology ,chemistry ,Statin Therapy ,Hydroxymethylglutaryl-CoA Reductase Inhibitor ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known.METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years.RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (PCONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.).
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- 2015
9. NMR structure of human DCL-1 (CD302) extracellular domain
- Author
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Pospisilova, E., primary, Kukacka, Z., additional, Kavan, D., additional, Novak, P., additional, and Chmelik, J., additional
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- 2017
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10. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes.
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IMPROVE-IT Investigators, Musliner, T., Tershakovec, A., Gurfinkel, E., Aylward, P., Tonkin, A., Maurer, G., Van de Werf, F., Nicolau, J.C., Theroux, P., Genest, J., Armstrong, P., Corbalan, R., Isaza, D., Spinar, J., Grande, P., Voitk, J., Kesaniemi, A., Bassand, J.P., Farnier, M., Darius, H., Keltai, M., Mathur, A., Mittal, S., Reddy, K., Lewis, B., De Ferrari, G.M., Ophuis, T.O., Jukema, J., White, H., Pedersen, T., Britto, F., Ruzyllo, W., Carrageta, M., Duris, T., Dalby, A., Seung, K.B., Lopez-Sendon, J., Dellborg, M., Mach, F., Guneri, S., Parkhomenko, A., Brady, A., Cannon, C., Blazing, M., Ballantyne, C., de Lemos, J., Kleiman, N., McGuire, D.K., Centeno, E., Casalins, M., Cartasegna, L., Beltrano, M.C., Guerrero, R., Fanuele, M., Berra, F., Egido, J., Colombo, H., Dellatorre, M., Terns, P., Blumberg, E., Reges, P., Azize, G., Ramos, H., Fernandez, R., Carlessi, C., Milesi, R., Schmuck, R., Duronto, E., Procopio, G., Carlevaro, O., Maffeo, H., Beloscar, J., Viso, M., Hominal, M., Castoldi, M., Bluguermann, J., Mauro, D., Macin, S., Cocco, N., Ruiz, N., Ricart, J., Lozada, A., Nani, S., Turri, D., Fernandez, H., Caruso, O., Zarandon, R., Bono, J., Arias, V., Allall, O., Marino, J., Cusimano, S., Schygiel, P., Buzetti, C., Penaloza, N., Berli, M., Worthley, S., Roach, A., Chew, D., Wright, T., Leitch, J., Hicks, E., Rankin, J., Venn-Edmonds, C., Lehman, R., Morrison, H., Shaw, J., Mak, V., Hii, C., Smith, K., Cross, D., Lilwall, L., Nelson, G., Loxton, A., Horowitz, J., Rose, J., Steinwender, C., Leisch, F., Kammler, J., Brussee, H., Zweiker, R., Niederl, E., Weihs, W., Giorgio, G., Lang, I., Drexel, H., Zanolin, D., Hoppe, U., Atzenhofer-Baumgartner, K., Pichler, M., Hainzer, D., Eber, B., Pichler, F., Foeger, B., Wechselberger, T., Mayr, H., Hofer, J., Stockenhuber, F., Warlits, B., Huber, K., Egger, F., Weidinger, F., Ziegler, B., Jirak, P., Metzler, B., Pachinger, O., Wanitschek, M., Auer, J., Grabscheit, G., Podczeck-Schweighofer, A., Priesnitz, T., Frank, H., El Allaf, D., Marechal, P., Roosen, J., Joly, E., Lefebvre, P., Arend, C., Sinnaeve, P., De Velder, L., Hellemans, S., Vanhauwaert, B., Van Dorpe, A., Heyse, A., Vantomme, C., Striekwold, H., Van Den Broeck, D., Lancellotti, P., Schoors, D., Lemoine, I., Taeymans, Y., De Wolf, L., Brike, C., Vercauteren, S., Tahon, S., Vervoort, G., Mestdagh, I., Pirenne, B., Cardinal, F., Lips, S., Dujardin, K., Debrouwer, K., Dhooghe, G., Holvoet, G., van de Borne, P., Renard, M., De Clippel, M., Lesseliers, H., Van Miert, N., Saraiva, J., Vicente, C., Rossi, P., Dos Santos, L.B., Duda, N., Tognon, A.P., Serrano, C., Gomes, F.L., Manenti, E.R., Silveira, D.S., Maia, L., Mouco, O.M., Paiva, M., Antonangelo, A., de Souza, J., Lino, E.A., Leães, P., Blacher, M.G., Kormann, A., Ultramari, F.T., Dutra, O., Mendelski, A.M., Morgado, S., Ardito, W., Greque, G., Ardito, R.V., Pimentel Filho, P., Zucchetti, C., Alves, A., Seabra, A.M., Mattos, M., Miranda, L.F., Silva, D., Uehara, R.M., Marin Neto, 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J.G., van Rossum, P., Stuij, S., Scott, R., Richards, A.M., Morrison, Z., Devlin, G., Fisher, R., Stewart, R., Benetar, J., Voss, J., Wong, S., Scott, D., Luke, R., Tang, E., Davidson, L., Hamer, A., Wilson, S., Price, R., Hart, H., Turner, A., Jortveit, J., Calic, S., Gundersen, T., Brunvand, H., Fosse, L., Nygaard, O., Gjellefall, B., Gravdal, S.A., Ringstad, R., Atar, D., Clausen, H., Hysing, J., Arvesen, K., Topper, M., Flagstad, E., Graven, T., Haug, H.H., Dalin, L., Al-Ani, R., Otterstad, J., Ausen, K., Aaser, E., Olufsen, M., Halvorsen, S., Gullestad, L., Stueflotten, W., Waage, K., Stødle, R.M., Hall, C., Aase, O., Nordeng, J., Soyland, E., Fageraas, E.R., Lied, A., Aske, R., Raouf, N., Johansson, J., Herrscher, T., Skogrand, E., Bjornstad, H., Aagnes, I., Arntsen, B.I., Vegsundvaag, J., Skjold, M.E., Velle, H., Aambakk, M.B., Skjetne, O., Byfuglien, A., Rodriguez, J., Galvez, D., Medina, F., Hernandez, H.A., Chavez, V., Morales, R., Huapalla, E., Velasquez, D., Torres, F., Aguirre, O., Yanez, L., Andrade, M., Campos, C., Arce, R., Mogrovejo, W., Osores, F., Bustamante, G., Rodriguez, M., Berrospi, P., Garcia, C., Talledo, M., Navarro, P., Horna, M., Herrera, V., Kadziela, J., Rybicka-Musialik, A., Trusz-Gluza, M., Berger-Kucza, A., Musial, W., Tycinska, A., Gil, R., Gziut, A., Gorny, J., Tyllo, M., Reszka, Z., Mickiewicz-Pawlowska, M., Wrzosek, B., Kosior, J., Staneta, P., Korzeniak, R., Kalarus, Z., Markowicz, E., Miekus, P., Konarzewski, M., Kleinrok, A., Puzniak, M., Grajek, S., Janus, M., Krzyzanowski, M., Hoffmann, A., Muzalewski, P., Polonski, L., Kazik, A., Nowalany-Kozielska, E., Wojciechowska, C., Ponikowski, P., Nawrocka, S., Filipiak, K., Serafin, A., Dubiel, J., Mielecki, W., Ogorek, M., Kopcik, D., Jaworska, K., Skonieczny, G., Kawecka-Jaszcz, K., Bryniarski, L., Tracz, W., Lesniak-Sobelga, A., Jankielewicz, J., Zaluska, R., Trojnar, R., Kawalek, P., Gaciong, Z., Pulkowski, G., Anaszewicz, M., Samul, W., Adamus, J., Cholewa, M., Kubik, L., Szczechowicz, R., Rekosz, J., Kwiatkowska, D., Gajek, J., Mazurek, W., Kominek, M., Siminiak, T., Guzniczak, E., Monteiro, P., Providencia, L., Monteiro, S., Pinho, T., Gavina, C., Sousa, C., Loureiro, J., Ferreira, A.R., Cardoso, A., Araujo, J., Rebolo, I., Catarino, C., Santos, J., Nunes, L.P., Mimoso, J., Marques, N., Leitao, M., Pais, J., Fernandes, A., Diogo, A., Nóbrega, J., Moreira, J.I., Mateus, P., Oliveira, J., Selas, M., Ribeiro, V., Albuquerque, A., Reis, R., Ramos, A., Salazar, F., Nair, D., Ng, C.K., Yeo, D., Wong, A., Funiak, S., Belicova, M., Striezova, I., Krajci, P., Sojka, G., Herman, O., Zemberova, A., Pella, D., Fedacko, J., Banikova, A., Micko, K., Macek, V., Moscovic, M., Vahala, P., Vykoukalova, T., Dzupina, A., Marusakova, M., Stevlik, J., Akubzanova, E., Hatalova, K., Burgess, L., Coetzee, C., Mabin, T., Roos, J., Mohamed, Z., Pillay, T., Corbett, C., Bodenstein, W., Tayob, F., Ebrahim, I., Bolsman, C., Horak, A., Lloyd, E., Pretorius, M., Commerford, P., De Andrade, M., Roux, J., Murray, A., Soma, P., Delport, E., Cassel, G., Van Zyl, L., Cronje, T., Sarvan, M., Moodley, R., Guerra, M., Swanepoel, N., Bayat, J., Klug, E., Hellig, S., Yoon, J., Kim, J., Chung, W., Choi, Y., Cho, M., Lee, S., Kwon, H., Hong, B., Seung, K., Chang, K., Rha, S., Jeong, M.H., Hong, Y., Lee, C., Seong, I., Jeong, J., Tahk, S., Yoon, M., Chae, S.C., Kim, H., Lopez, V., Roldan, J.M., Mancisidor, P., Froufe, J., López, A., Franco, S., Molina, A., Soriano, F., Cobos, M., Mejía, H.D., Sanz, R., Vazquez, A., Garri, F., Esteban, I., Marco, P., Artaecheverria, J., Cequier, A., Esplugas, E., Gonzalez, J., de Sa, E., Armada, E., Worner, F., Hernández, I., Roncales, F., Gomollon, J., del Rio, A., Alameda, J., Basilio, E., Rafols, M., Ferres, R., Molla, C., Pascual, J., Cortada, J., García, C., Iglesias, G., Villa, E., Aros, F., Goya, I., Bueno, M., Pereira, R.V., Clavero, X., Pasaron, C.D., Jorda, R., Pereira, R., Perez, O., de Teresa, E., Navarro, M., de la Guia, F., Lozano, T., Antorrena, I., Aranda, M., Alonso, L., Mirelis, J., Alcasena, S., Paniagua, V.A., Juanatey, J., Gregorian, L., Munoz, J., Escorihuela, A., Sanz, A., Flores, A., Garcia, P.A., Alfonso, F., Marin, E., Lozano, A., Bethencourt, A., Grau, A., Rubio, A., Sala, J., Royuela, N., San Jose, J., Bugos, V., de Valdecilla, H., Martin, J., Jimenez, R., Felgueres, M., Escalera, P., Ruiz, R., Bescos, L., Sanchez, I., Chavarri, M., Casares, G., Johanson, P., Hultsberg-Olsson, G., Witt, N., Samad, B., Damm, T., Risenfors, M., Ortgren, L., Henareh, L., Jernberg, T., Berglund, M., Karlsson, J., Koch, A., Lycksell, M., Lundgren, C., Herlitz, J., Sjölin, M., Erlinge, D., Matson, E., Cizinsky, S., Carlsson, F., Ryttberg, B., Johansson, K., Tygesen, H., Bergsten, J., Naslund, U., Sundholm, C., Timberg, I., Wikström, P., Hårdhammar, P., Lisbeth, A., Lund, L., Hage, C., Rosenqvist, U., Grändås, M., Larsson, L., Hammerman, A., Andersson, G., Johansson, S., Bennermo, M., Tjerneld, H., Forsgren, M., Eriksson, K., Eriksson, M., Bengtsson, P.O., Yu, W., Ceder-Brolin, K., Stafberg, C., Andersson, E., Roussine, V., Ångman, K., Melin, B., Thorsen, S., Lundell, L., Buijs, F., Östberg, S., Sigaud, P., Moccetti, T., Bondio, M., Kuehlkamp, V., Pieper, M., Gallino, A., Zender, H., Genné, D., Gauthey, J., Wilhelm, M., Saner, H., Trachsel, L., Roethlisberger, C., Schlaepfer, H., Kujawski, T., Pagnamenta, A., Meyer-Monard, S., Krapf, R., Biedermann, B., Schneider, H., Rickli, H., Ramsay, D., Linka, A., Ballmer, P., Oswald, M., Girod, G., Charng, M., Shu-Ling, H., Ping-Han, L., Wu, C., Liu, S., Lin, M., Chian-Yi, W., Yeh, H., Mei-Juan, C., Hsieh, I., Wang, Y., Ural, E., Sahin, T., Yildiz, Z., Kayikcioglu, M., Kultursay, H., Yigit, Z., Calpar, I., Ata, N., Goktekin, O., Senol, U., Yalcin, R., Timurkaynak, T., Kaya, U., Yildirir, A., Karacaglar, E., Faynyk, A., Sorokivskyy, M., Koval, O., Kaplan, P., Kraiz, I., Popova, K., Kyyak, Y., Barnett, O., Karpenko, O., Todoriuk, L., Tseluyko, V., Kopytsya, M., Petyunina, O., Kovalskyy, I., Zhukova, Y., Katerenchuk, I., M'yakinkova, L., Lutay, Y., Syvolap, V., Kyselov, S., Vakaliuk, I., Nesterak, R., Nikonov, V., Feskov, O., Goloborodko, B., Golovtsev, Y., Berezniakov, I., Lebedynska, M., Rudenko, L., Tutov, I., Ahsan, A., Burton, J., Levy, T., Lakeman, N., Spratt, J., Langford, E., Sutcliffe, S., Khwanda, A., Davis, G., Rodrigues, E., Dickinson, D., Been, M., Trouton, T., Riddell, J., Moriarty, A., McEneaney, D., Squire, I., Narayan, H., Goode, G., Helliwell, L., Boos, C., Greaves, K., Knops, K., Pegge, N., Signy, M., Wong, Y., Moore, S., Fluck, D., Atkinson, C., Adgey, A., McKeag, N., Bishop, A., Glover, J., Barbir, M., Breen, J., Robson, H., Townend, J., Dwenger, E., Ekpo, E., Shakespeare, C., Barr, C., McClements, B., McAllister, A., De Belder, M., Cooke, J., Williams, S., Daniel, D., Pye, M., Griffith, K., Wright, L., Trevelyan, J., Doughty, A., Hughes, E., Phillips, C., Penny, W., Groves, P., Kardos, A., Purvis, J., McNeill, A., Jones, A., Brown, J., Saeed, B., Sprigings, D., Herity, N., Brown, C., Unks, M., Cauthren, T., Bertolet, B., Jones, M., Decker, S., Chambers, J., Stahlberg, J., Varma, S., Gencheff, N., Price, A., McElroy, D., Chu, A., Crutchfield, B., Eaton, G., Looney, A., Qureshi, M., Wilks, J., Drenning, D., Overman, A., Andreou, C., Russo, P., Stuckey, T., Pruitt, H., D'Urso, M., DeRaad, R., Rogers, W., Thorington, S., Pasquini, J., Iwaoka, R., Tannenbaum, M., Prouty, D., Wiseman, A., Sharow, A., Graham, B., Ali, M.I., Dale, H., Tarsi, D., Picone, M., Juarez, S., Hamroff, G., Hollenweger, L., Scirica, B., Sabatine, M., Marti, J., Perlman, R., Pavlides, A., Joffe, I., Albirini, A., Campbell, T., Puri, S., Lopez, C., Pearce, D., Shah, D., McPherson, J., Donegan, R., Murdock, D., Block, D., Malik, A., Musina, R., Dauber, I., Varner, C., Bach, R., Palazzolo, M., Bhalla, H., Thompson, M., Pollock, S., Johnson, S., Lipson, L., Brunk, S., Karas, S., Vicari, R., Kuvin, J., Mooney, P., Aycock, G., Lane, B., Sharma, M., Gibson, T., Chang, G., DiVito, P., Mehta, R., Watkins, K., Chiu, A., Gunderson, J., Tedder, B., Williams, P., Hage-Korban, E., Childs, A., Banerjee, S., Kazi, F., Bennett, J., Barnes, D., Wohns, D., Noorman, C., Aggarwal, K., Lau-Sickman, A., Paulowski, J., Amos, M., Rider, J., Fenton, S., Schantz, M., Hakas, J., Mcsorley, J., Felten, W., Bitzer, V., Russell, J., Loyo, J., Adjei, A., Mehta, K., Uretsky, B., Hale, M., Shaikh, S., Miller, M., Hollenbaugh, D., Crawford, K., Fortuin, D., Galindo, A., Del Core, M., Butkus, E., Collins, J., Prior, J., Hahn, R., Greene-Nashold, J., Alexander, J., Genova, E., MacDonell, A., Broadwater, S., Kereiakes, D., White, D., Lopez, M., Schenks, R., Lui, H., Gibbons, P., Davis, B., Thornton, K., Daley, P., Budzon, S., McCullum, K., Delio-Cox, B., Nadar, V., Keim, S., McLaurin, B., Davis, C., Betzu, R., Al-Jumaily, J., Bolli, R., Alshaher, M., Leesar, M., Collins, T., Akkad, H., Bilazarian, S., Marsters, M., Kennett, J., Melegrito, K., Mostel, E., Harris, R., Chang, M., Hatfield, G., Makam, S., Garvey, M., Levite, H., White, J., Abdel-Latief, A., Pelletier, L., Carr, K., Mckenna, K., De Lemos, J., Soto, G., Kozina, J., Harris, D., Vlastaris, A., Bittel, B., Riba, A., Gugudis, J., Singh, N., Qureshi, I., Doty, W., Lehmann, J., Lieber, I., Martin, S., Nicu, M., Bhalodkar, N., Ravi, P., Canto, J., Bass, M., Campbell, C., Steinhubl, S., Moles, K., Harjai, K., Stapleton, D.D., Hoey, K., Erwin, J., Fikes, W., Stein, B., Sabatino, K., Teklinski, A., Colfer, H., Ward, P., Langevin, E., Faucett, S., Mamdani, S., DeSimone, L., Tuohy, E., Cullen, T., Eisenberg, S., Chronos, N., Allen, R.P., Erickson, B., Mahon, K., Kirby, A., Siegel, C., Stroud, L., Johnson, J., Panchal, V., Pearson, A., Abell, T., De Gregorio, M., Boomer, L., Vahdat, O., VanNatta, B., Long, P., Chalavarya, G., Skatrud, L., Carey, C., Wright, W., Mechem, C., Matthews, B., Adams, A., Vora, K., Wead, J., Koren, M., Gregory, D., El Khadra, M., 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K., Bayles, A., Masroor, M., North, W.K., Fishberg, R., Merveil-Ceneus, B., Butcher, R., Menapace, F., Kilbride, S., Ramabadran, R.S., Loukinen, K., Khalil, J., Ramabadran, R., Walsh, S., Gill, S., Cyncar, R., McLachlan, J., Surakanti, V., Rusterholtz, L., Shoukfeh, F., Stephenson, L., Tsang, M., Nolan, V., Gilchrist, I., Jefferson, D., Feldman, T., Reyes, L., Santos, R., Little, W., Wesley, D., Gharib, W., Mendell, A., Esham, G., Kakavas, P., Whitcomb, C., Book, K., Bazzi, A., Alvarez, J., Cohen, Y., Ayres, T., Rhule, V., Labib, A., Schuler, P., Zughaib, M., Telck, K., Bikkina, M., Turnbull, K., Sharma, T., Orosz, S., Shah, R., Petrino, M., Hughes, M., Hershey, J., Hudock, D., Hui, P., Von Bakonyi, A., Arnold, A., Kappel, D., Pennock, G., Cloud, B., Tucker, K., Harp, L., Hoover, C., Eisenhauer, M., Roth, J., Young, C., Thai, H., Escalante, A., Bautista, J., Gazmuri, R., Nyland, J., Cubeddu, L., DeFranco, A., Dias, D., Fielding, M., Reeves, R., Hermany, P., Meissner-Dengler, S., Evans, M., Flores, E., Tannenbaum, A., McGarr, K., Moran, J., Stout, E., Allred, S., Henderson, D., Crandall, L., Strote, J., Voyles, W., Robeson, D., Bedoya, R., Omar, B., Pettyjohn, F., Revere, C., Coy, K., Margolis, J., Sotolongo, C., Scheffel, M., Munir, A., Shirwany, A., Douglas, L., Girala, R., Humphreys, R., Agarwal, J., Bankowski, D., Watson, R., Bishop, B., Klementowicz, P., Blais, D., Cohen, B., Lobur, E., Dimenna, J., Dempsey, K., Izzo, M., Bondi, L., Carell, E., Eaton, C., Saltiel, F., Grewal, G., Connolly, T., Little, T., Wiegman, P., Gips, S., Held, J., Paraschos, A., Quesada, R., Goudreau, E., Sears, M., Istfan, P., Holt, S., McClung, J., Nguyen, N., Quintana, O., Gottlieb, D., Knutson, T., Barringhaus, K., Lester, F., Sullivan, P., Rodriguez-Ospina, L., Cannon, C.P., Blazing, M.A., Giugliano, R.P., McCagg, A., White, J.A., Lewis, B.S., Jukema, J.W., De Lucca, P., Im, K., Bohula, E.A., Reist, C., Wiviott, S.D., Tershakovec, A.M., Musliner, T.A., Braunwald, E., Califf, R.M., IMPROVE-IT Investigators, Musliner, T., Tershakovec, A., Gurfinkel, E., Aylward, P., Tonkin, A., Maurer, G., Van de Werf, F., Nicolau, J.C., Theroux, P., Genest, J., Armstrong, P., Corbalan, R., Isaza, D., Spinar, J., Grande, P., Voitk, J., Kesaniemi, A., Bassand, J.P., Farnier, M., Darius, H., Keltai, M., Mathur, A., Mittal, S., Reddy, K., Lewis, B., De Ferrari, G.M., Ophuis, T.O., Jukema, J., White, H., Pedersen, T., Britto, F., Ruzyllo, W., Carrageta, M., Duris, T., Dalby, A., Seung, K.B., Lopez-Sendon, J., Dellborg, M., Mach, F., Guneri, S., Parkhomenko, A., Brady, A., Cannon, C., Blazing, M., Ballantyne, C., de Lemos, J., Kleiman, N., McGuire, D.K., Centeno, E., Casalins, M., Cartasegna, L., Beltrano, M.C., Guerrero, R., Fanuele, M., Berra, F., Egido, J., Colombo, H., Dellatorre, M., Terns, P., Blumberg, E., Reges, P., Azize, G., Ramos, H., Fernandez, R., Carlessi, C., Milesi, R., Schmuck, R., Duronto, E., Procopio, G., Carlevaro, O., Maffeo, H., Beloscar, J., Viso, M., Hominal, M., Castoldi, M., Bluguermann, J., Mauro, D., Macin, S., Cocco, N., Ruiz, N., Ricart, J., Lozada, A., Nani, S., Turri, D., Fernandez, H., Caruso, O., Zarandon, R., Bono, J., Arias, V., Allall, O., Marino, J., Cusimano, S., Schygiel, P., Buzetti, C., Penaloza, N., Berli, M., Worthley, S., Roach, A., Chew, D., Wright, T., Leitch, J., Hicks, E., Rankin, J., Venn-Edmonds, C., Lehman, R., Morrison, H., Shaw, J., Mak, V., Hii, C., Smith, K., Cross, D., Lilwall, L., Nelson, G., Loxton, A., Horowitz, J., Rose, J., Steinwender, C., Leisch, F., Kammler, J., Brussee, H., Zweiker, R., Niederl, E., Weihs, W., Giorgio, G., Lang, I., Drexel, H., Zanolin, D., Hoppe, U., Atzenhofer-Baumgartner, K., Pichler, M., Hainzer, D., Eber, B., Pichler, F., Foeger, B., Wechselberger, T., Mayr, H., Hofer, J., Stockenhuber, F., Warlits, B., Huber, K., Egger, F., Weidinger, F., Ziegler, B., Jirak, P., Metzler, B., Pachinger, O., Wanitschek, M., Auer, J., Grabscheit, G., Podczeck-Schweighofer, A., Priesnitz, T., Frank, H., El Allaf, D., Marechal, P., Roosen, J., Joly, E., Lefebvre, P., Arend, C., Sinnaeve, P., De Velder, L., Hellemans, S., Vanhauwaert, B., Van Dorpe, A., Heyse, A., Vantomme, C., Striekwold, H., Van Den Broeck, D., Lancellotti, P., Schoors, D., Lemoine, I., Taeymans, Y., De Wolf, L., Brike, C., Vercauteren, S., Tahon, S., Vervoort, G., Mestdagh, I., Pirenne, B., Cardinal, F., Lips, S., Dujardin, K., Debrouwer, K., Dhooghe, G., Holvoet, G., van de Borne, P., Renard, M., De Clippel, M., Lesseliers, H., Van Miert, N., Saraiva, J., Vicente, C., Rossi, P., Dos Santos, L.B., Duda, N., Tognon, A.P., Serrano, C., Gomes, F.L., Manenti, E.R., Silveira, D.S., Maia, L., Mouco, O.M., Paiva, M., Antonangelo, A., de Souza, J., Lino, E.A., Leães, P., Blacher, M.G., Kormann, A., Ultramari, F.T., Dutra, O., Mendelski, A.M., Morgado, S., Ardito, W., Greque, G., Ardito, R.V., Pimentel Filho, P., Zucchetti, C., Alves, A., Seabra, A.M., Mattos, M., Miranda, L.F., Silva, D., Uehara, R.M., Marin Neto, 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David, M., Giannoccaro, J., Beresford, P., Polasek, P., Roberts, P., Doucet, M., Beaudry, M., Cheung, S., Cleveland, T., Bhargava, R., McCallum, A., Ma, P., Morrissette, J., Cleveland, D., Chadwyn, D., Nigro, F., Weeks, A., Cryderman, C., Leader, R., Houde, G., Rousseau, S., Pearce, M., Radyk, M., Lonn, E., Magi, A., Lefkowitz, C., Sandrin, F., Coffin, N., Lubelsky, B., Coldwell, J., Habot, J., McPherson, C., De Larochelliere, R., Roy, M., Haichin, R., Barber, C., Bhesania, T., Kitagawa, H., To, T., Donnelly, B., Tymchak, W., Harris, L., Kouz, S., Huynh, T., St Jacques, B., Lamy, A., Rizzo, A., Stein, J., Childs, C., Wong, B., Poirier, R., Gupta, M., Dela Cruz, C., Constance, C., Gauthier, M., Ervin, F., Ouellette, M., Kokis, A., Lemay, C., Kwok, K., Leung, C., Lee, D., Nesmith, J., Renton, J., Syan, G., Turek, M., Hogan, D., Griffin, P., Lipson, A., Winestock, J., Abramson, B., Fogel, A., Gagne, C., Bergeron, J., Clarke, A., Slipp, S., Darcel, I., Carling-Chambers, L., Kannampuzha, P., Pallie, S., Krekorian, S., Vertes, G., Roth, S., Lai, K., Heath, J., Perez, L., Arriagada, G., Castro, P., Villa, F., Rodríguez, M., Ramos, G., Baraona, F., Núñez, A., García, M., Jofre, C., Silva, P., Lamich, R., Yovaniniz, P., Escobar, E., Dussaubat, A., Segura, E., Ramirez, M., Lapostol, C., Palma, A., Encina, L., Zapata, M., Baeza, N., Varela, P., Pérez, L., Jaramillo, C., Ruiz, S., Sanchez, G., Perdomo, I., Manzur, F., Cohen, L.E., Velasquez, J., Arana, C., Alvarez, Y., Triana, M., Balaguera, J., de Salazar, D., Rendon, N., Botero, R., Ruiz, A., Saaibi, J., Medina, J., Jaramillo, M., Calderón, M.J., Delgado, J., Bohorquez, R., Medina, M.F., Herrera, M., Rosales, D., Mendoza, F., Martinez, S., Ternera, A., Castro, R., Baiz, A., Martinez, M., Orozco, A., Suarez, M., Fonseca, Y., Beltran, R., Cepeda, M., Jaramillo, N., Valenzuela, C., Gutierrez, M., Sanchez, A., Vitovec, J., Hlinomaz, O., Poloczek, M., Mayer, O., Veselka, J., Vejvoda, J., Soucek, M., Spac, J., Novobilsky, K., 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Szelényi, Z., Polgár, P., Svab, S., Herczeg, B., Bajcsi, É., Vértes, A., Davidovits, S., Nagy, A., Király, C., Lupkovics, G., Kenéz, A., Poór, F., Takács, J., Kirschner, R., Simonyi, G., Koncz, J., Édes, I., Gergely, S., Katona, A., Nagy, E., Kovács, Z., Gyetvai, I., Salamon, C., Kolman, É., Sitkei, É., Csapó, K., Molnar, K., Mező, I., Sereg, M., Reddy, P., Manjunath, C., Narayanappa, S., Kumar, S., Sinha, N., Kapoor, A., Christopher, J., Reddy, G., Rani, M., Oomman, A., Ramamurthee, K., Kumar, N., Pasha, S.S., Rao, C., Murty, G.S., Chopra, A., Kapila, D., Bali, H., Chattree, K., Hasan, O., Suryaprakash, G., Rao, D., Babu, R., Bhargavi, M., Naik, S., Khan, S., Chopra, V., Sapra, R., Kaul, U., Ghose, T., Menon, R., Battikadi, S., Mullasari, A., Subban, V.K., Dani, S., Iby, M., Chandra, P., Sethi, S., Bhargava, M., Arora, P., Tyagi, G., Padmanabhan, T., Malhotra, S., Talwar, K., Shafiq, N., Kasliwal, R., Bansal, M., Eldar, M., Berger, M., Shechter, M., Atar, S., Roguin, N., Kilimnik, M., 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Ieva, R., Fattore, L., Cicia, G., Cavallini, C., Tamburino, C., Sacco, A., Mafrici, A., Di Pasquale, G., Pavesi, P.C., Scioli, R., Lioy, E., Occhiuzzi, E., Matino, M.G., Russo, V., Moscogiuri, M.G., Cuccia, C., Forgione, C., Volpe, M., Palano, F., Branca, G., Rossi, R., Modena, M., Olaru, I.A., Zanini, R., Cianflone, D., Cristell, N., Pantaleoni, M., Guiducci, U., Menozzi, C., Gaddi, O., Fasulo, A., Indolfi, C., Emanuele, V., Guerra, F., Iliceto, S., Marotta, C., Morocutti, G., Presbitero, P., Rossi, M., Bonatti, S., Grieco, A., Chiodi, L., Betti, I., Zuppiroli, A., Fanelli, R., Stanco, G., Azzolini, P., Ruggieri, C., Bocconcelli, P., Airoldi, F., Tavano, D., Brunelli, C., Caso, P., Scalzone, A., Ghigliotti, G., Facciorusso, A., Sim, K., Kiam, O., Chee, K., Bin Ismail, O., Zambahari, R., Ophuis, T., van Nes, E., Werter, C.J., Ophuis, A.J., Troquay, R.P., Hamer, B.J., Lenderink, T., Feld, R.J., van Hessen, M.W., Viergever, E.P., van der Sluis, A., Lok, D.J., Badings, E.A., Nierop, P.R., Danse, I.Y., Hermans, W.R., Holwerda, N.J., Thijssen, H.J., Theunissen, L.J., van der Zwaan, C., Van Den Berg, B.J., Hendriks, I.H., Ronner, E., Withagen, A.J., Dijkshoorn-Giesen, A.H., Ezechiels, J.P., Kuijper, A.F., Den Hartog, F.R., Van Kalmthout, P.M., Buijs, E.M., van der Zeijst, M., Zwart, P.A., Zuidgeest, J.A., van Eck, M., Daniels, M.C., van der Ven-Elzebroek, N., Van 't Hof, A., van Boven, A.J., van der Weerdt, A., Dunselman, P.H., Alings, M.A., van Es, R.F., The, S.H., Gurlek, C., Liem, A.H., van Lennep, H.W., Van Vlies, B., Kalkman, C., Swart, H.P., van der Bij, P., Taverne, R., Ciampricotti, R., van Dam, C., Spierenburg, H., van Ruijven, I., van Kempen, L.H., Willems, F.F., Dirkali, A., Stoel, I., Plomp, J., Veldmeijer, S., Tjeerdsma, G., Nijmeijer, R., Van Hal, J.M., Bartels, G.L., Posma, J.L., Linssen, G.C., Fauser, C.G., Waalewijn, R.A., Groenemeijer, B.E., Pos, L., Fast, J.H., Droste, H.T., Westenburg, J., Veenstra, W., Koolen, J., van Loo, L.W., Smits, W., Milhous, J.G., van Rossum, P., Stuij, S., Scott, R., Richards, A.M., Morrison, Z., Devlin, G., Fisher, R., Stewart, R., Benetar, J., Voss, J., Wong, S., Scott, D., Luke, R., Tang, E., Davidson, L., Hamer, A., Wilson, S., Price, R., Hart, H., Turner, A., Jortveit, J., Calic, S., Gundersen, T., Brunvand, H., Fosse, L., Nygaard, O., Gjellefall, B., Gravdal, S.A., Ringstad, R., Atar, D., Clausen, H., Hysing, J., Arvesen, K., Topper, M., Flagstad, E., Graven, T., Haug, H.H., Dalin, L., Al-Ani, R., Otterstad, J., Ausen, K., Aaser, E., Olufsen, M., Halvorsen, S., Gullestad, L., Stueflotten, W., Waage, K., Stødle, R.M., Hall, C., Aase, O., Nordeng, J., Soyland, E., Fageraas, E.R., Lied, A., Aske, R., Raouf, N., Johansson, J., Herrscher, T., Skogrand, E., Bjornstad, H., Aagnes, I., Arntsen, B.I., Vegsundvaag, J., Skjold, M.E., Velle, H., Aambakk, M.B., Skjetne, O., Byfuglien, A., Rodriguez, J., Galvez, D., Medina, F., Hernandez, H.A., Chavez, V., Morales, R., Huapalla, E., Velasquez, D., Torres, F., 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- Abstract
Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years. The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016). Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benef
- Published
- 2015
11. NMR structure of the lymphocyte receptor NKR-P1A
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Chmelik, J., primary, Rozbesky, D., additional, Pospisilova, E., additional, Adamek, D., additional, and Novak, P., additional
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- 2015
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12. NMR structure of the lymphocyte receptor NKR-P1A
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Chmelik, J., primary, Rozbesky, D., additional, Pospisilova, E., additional, and Novak, P., additional
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- 2014
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13. ID 157 – EEG source monitoring of alfa activity during qi gong practice
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Pánek, D., Kovářová, L., Krajča, V., Brunovský, M., Pavlů, D., and Pospíšilová, E.
- Published
- 2016
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14. 18. The occurrence of alpha activity during cyclical repetitive movement
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Pánek, D.L., Kovářová, L., Pavlů, D., Krajča, V., and Pospíšilová, E.
- Published
- 2015
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15. Sesquiterpenes α-humulene and β-caryophyllene oxide enhance the efficacy of 5-fluorouracil and oxaliplatin in colon cancer cells
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Ambrož Martin, Šmatová Markéta, Šadibolová Michaela, Pospíšilová Eva, Hadravská Pavlína, Kašparová Michaela, Skarková Veronika Hanušová, Králová Věra, and Skálová Lenka
- Subjects
terpenes ,caco-2 ,sw-620 ,combination therapy ,Pharmaceutical industry ,HD9665-9675 - Abstract
The present study is designed to find out if sesquiterpenes, α-humulene (HUM), valencene (VAL), β-caryphyllene-oxide (CAO) and trans-nerolidol (NER), are able to improve the antiproliferative effect of classical cytostatic drugs, 5-fluorouracil (FU) and oxaliplatin (1,2-diaminocyclohexaneoxalato-platinum, OxPt), in colon cancer cell lines Caco-2 and SW-620. In addition, the possible mechanisms of sesquiterpene action are studied. The results show significant ability of HUM and especially of CAO to enhance the anti-proliferative effects of FU and OxPt in cancer cell lines Caco-2 and SW-620. On the other hand, VAL and NER are ineffective. The action of CAO could be partly based on its ability to disrupt the mitochondrial membrane potential and to activate initiator caspases, but other mechanisms are probably also involved. Based on these results, CAO seems to have the potential for combination therapy of colon cancers and deserves further study.
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- 2019
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16. Reduction of postincisional allodynia by subcutaneous bupivacaine: findings with a new model in the hairy skin of the rat.
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Duarte AM, Pospisilova E, Reilly E, Mujenda F, Hamaya Y, Strichartz GR, Duarte, Adriana M, Pospisilova, Eva, Reilly, Erin, Mujenda, Florence, Hamaya, Yoshihiro, and Strichartz, Gary R
- Published
- 2005
17. PRENATAL DIAGNOSIS IN TWO FAMILIES WITH METHYLMALONIC ACIDEMIA DUE TO COBALAMIN B DEFICIENCY
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Pospisilova, E., Mrazova, L., Priby, D., Chrastina, P., Soucek, R., Martincova, O., Sylvie Šťastná, Halova, K., Kantarska, D., Gregova, E., Kosarova, M., Chodorova, I., Dvorakova, H., Elleder, M., and Zeman, J.
18. Ornithine transcarbamylase deficiency with organic acid pattern mimicking long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
- Author
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Kostalova, E., Sylvie Šťastná, Pospisilova, E., Dvorakova, L., and Zeman, J.
19. A0704 - Rapid feedback on the effects of anticancer mitochondrially targeted tamoxifen using circulating tumor cells.
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Klézl, P., Kolostova, K., Bielcikova, Z., Stursa, J., Werner, L., Neuzil, J., Balinthova, S., Dvorakova, S., Molnarova, L., Pospisilova, E., Gregusova, A., Sonsky, J., Grill, R., and Bobek, V.
- Subjects
- *
ANTINEOPLASTIC agents , *TAMOXIFEN - Published
- 2024
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20. 71 - Circulating tumor cells in renal cancer.
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Klézl, P., Sonsky, J., Grill, R., Pospisilova, E., Kolostova, K., and Bobek, V.
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- *
RENAL cancer , *CANCER cells , *VASCULAR endothelial growth factors , *SECONDARY primary cancer - Published
- 2019
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21. Circulating tumor cells in patients with cervical cancer undergoing chemoradiotherapy combined with brachytherapy.
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Reginacova K, Pospisilova E, Kubecova M, Svobodova P, Bobek V, and Kolostova K
- Abstract
Circulating tumor cells (CTCs) have significant potential to become an important tool for monitoring the effects of treatment in solid tumors. The present study reports the occurance of CTCs in cervical cancer (CC) patients during radical chemoradiotherapy (CRT), including brachytherapy (BRT), and during the follow-up period. Patients diagnosed with CC treated with radical CRT were included in the study (n=30). A total of 167 CTC-tests (MetaCell
® ) were provided at predefined testing time points during the study follow-up (e.g., before CRT, after CRT, every three months of follow-up). In parallel with CTC-testing, SCC-Ag were measured to compare their predictive values during treatment. CTCs were present in 96% (25/26) of patients at the time of diagnosis and in 61% (14/23) after treatment. Patients who relapsed during the 36-month follow-up (n=10) showed an elevation in pre-treatment CTC- numbers, similarly there was a significant increase in pre-treatment SCC-Ag. As next, an increased number of CTCs was observed approximately 12 weeks before relapse was diagnosed by standard imaging modalities (MRI, US, PET-CT) in 3 of 4 patients. In addition to standardized vital cytomorphology of enriched CTCs, quantitative PCR (qPCR) was used to inform the nature of CTCs before treatment. Analysis revealed increased SOX2 and POUSF expression in CTCs in the group of patients with recurrence (P < 0.02). Disease aggressiveness may be related to increased expression of stem cell markers, as found in samples from relapsed patients. CTCs may be an aid to assess tumor burden and disease aggressiveness. An increase in CTCs precedes an increase in SCC-Ag and confirmation of relapse by imaging, as shown in our study., Competing Interests: None., (AJCR Copyright © 2024.)- Published
- 2024
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22. Human bone marrow stromal cells: the impact of anticoagulants on stem cell properties.
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Ferencakova M, Benova A, Raska I Jr, Abaffy P, Sindelka R, Dzubanova M, Pospisilova E, Kolostova K, Cajka T, Paclik A, Zikan V, and Tencerova M
- Abstract
Background: Bone marrow stromal cells (BMSCs) are the source of multipotent stem cells, which are important for regenerative medicine and diagnostic purposes. The isolation of human BMSCs from the bone marrow (BM) cavity using BM aspiration applies the method with collection into tubes containing anticoagulants. Interactions with anticoagulants may affect the characteristics and composition of isolated BMSCs in the culture. Thus, we investigated how anticoagulants in isolation procedures and cultivation affect BMSC molecular characteristics. Methods: BM donors (age: 48-85 years) were recruited from the hematology clinic. BM aspirates were obtained from the iliac crest and divided into tubes coated with ethylenediaminetetraacetic acid (EDTA) or heparin anticoagulants. Isolated BMSCs were analyzed by flow cytometry and RNA-seq analysis. Further cellular and molecular characterizations of BMSCs including CFU, proliferation and differentiation assays, cytometry, bioenergetic assays, metabolomics, immunostaining, and RT-qPCR were performed. Results: The paired samples of isolated BMSCs obtained from the same patient showed increased cellular yield in heparin vs. EDTA samples, accompanied by the increased number of CFU colonies. However, no significant changes in molecular characteristics were found between heparin- and EDTA-isolated BMSCs. On the other hand, RNA-seq analysis revealed an increased expression of genes involved in nucleotide metabolism and cellular metabolism in cultivated vs. non-cultivated BMSCs regardless of the anticoagulant, while genes involved in inflammation and chromatin remodeling were decreased in cultivated vs. non-cultivated BMSCs. Conclusion: The type of anticoagulant in BMSC isolation did not have a significant impact on molecular characteristics and cellular composition, while in vitro cultivation caused the major change in the transcriptomics of BMSCs, which is important for future protocols using BMSCs in regenerative medicine and clinics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ferencakova, Benova, Raska, Abaffy, Sindelka, Dzubanova, Pospisilova, Kolostova, Cajka, Paclik, Zikan and Tencerova.)
- Published
- 2023
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23. Mitochondrially targeted tamoxifen in patients with metastatic solid tumours: an open-label, phase I/Ib single-centre trial.
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Bielcikova Z, Stursa J, Krizova L, Dong L, Spacek J, Hlousek S, Vocka M, Rohlenova K, Bartosova O, Cerny V, Padrta T, Pesta M, Michalek P, Hubackova SS, Kolostova K, Pospisilova E, Bobek V, Klezl P, Zobalova R, Endaya B, Rohlena J, Petruzelka L, Werner L, and Neuzil J
- Abstract
Background: Mitochondria present an emerging target for cancer treatment. We have investigated the effect of mitochondrially targeted tamoxifen (MitoTam), a first-in-class anti-cancer agent, in patients with solid metastatic tumours., Methods: MitoTam was tested in an open-label, single-centre (Department of Oncology, General Faculty Hospital, Charles University, Czech Republic), phase I/Ib trial in metastatic patients with various malignancies and terminated oncological therapies. In total, 75 patients were enrolled between May 23, 2018 and July 22, 2020. Phase I evaluated escalating doses of MitoTam in two therapeutic regimens using the 3 + 3 design to establish drug safety and maximum tolerated dose (MTD). In phase Ib, three dosing regimens were applied over 8 and 6 weeks to evaluate long-term toxicity of MitoTam as the primary objective and its anti-cancer effect as a secondary objective. This trial was registered with the European Medicines Agency under EudraCT 2017-004441-25., Findings: In total, 37 patients were enrolled into phase I and 38 into phase Ib. In phase I, the initial application of MitoTam via peripheral vein indicated high risk of thrombophlebitis, which was avoided by central vein administration. The highest dose with acceptable side effects was 5.0 mg/kg. The prevailing adverse effects (AEs) in phase I were neutropenia (30%), anaemia (30%) and fever/hyperthermia (30%), and in phase Ib fever/hyperthermia (58%) together with anaemia (26%) and neutropenia (16%). Serious AEs were mostly related to thromboembolic (TE) complications that affected 5% and 13% of patients in phase I and Ib, respectively. The only statistically significant AE related to MitoTam treatment was anaemia in phase Ib (p = 0.004). Of the tested regimens weekly dosing with 3.0 mg/kg for 6 weeks afforded the best safety profile with almost all being grade 1 (G1) AEs. Altogether, five fatalities occurred during the study, two of them meeting criteria for Suspected Unexpected Serious Adverse Events Reporting (SUSAR) (G4 thrombocytopenia and G5 stroke). MitoTam showed benefit evaluated as clinical benefit rate (CBR) in 37% patients with the largest effect in renal cell carcinoma (RCC) where four out of six patients reached disease stabilisation (SD), one reached partial response (PR) so that in total, five out of six (83%) patients showed CBR., Interpretation: In this study, the MTD was established as 5.0 mg/kg and the recommended dose of MitoTam as 3.0 mg/kg given once per week via central vein with recommended preventive anti-coagulation therapy. The prevailing toxicity included haematological AEs, hyperthermia/fever and TE complications. One fatal stroke and non-fatal G4 thrombocytopenia were recorded. MitoTam showed high efficacy against RCC., Funding: Smart Brain Ltd., Translation: For the Czech translation of the abstract see Supplementary Materials section., Competing Interests: J.N., J.S and L.W. are owners of MitoTax s.r.o. that co-owns the MitoTam intellectual property., (© 2023 The Author(s).)
- Published
- 2023
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24. Immune activation of the monocyte-derived dendritic cells using patients own circulating tumor cells.
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Kolostova K, Pospisilova E, Matkowski R, Szelachowska J, and Bobek V
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- Humans, Granulocyte-Macrophage Colony-Stimulating Factor pharmacology, Interleukin-4 pharmacology, Interleukin-6 pharmacology, Prostaglandins E pharmacology, Dendritic Cells metabolism, Monocytes metabolism, Neoplastic Cells, Circulating metabolism
- Abstract
Background: Dendritic cell (DC) therapy counts to the promising strategies how to weaken and eradicate cancer disease. We aimed to develop a good manufacturing practice (GMP) protocol for monocyte-derived DC (Mo-DC) maturation using circulating tumor cells lysates with subsequent experimental T-cell priming in vitro., Methods: DC differentiation was induced from a population of immunomagnetically enriched CD14 + monocytes out of the leukapheresis samples (n = 6). The separation was provided automatically, in a closed bag system, using CliniMACS Prodigy
® separation protocols (Miltenyi Biotec). For differentiation and maturation of CD14 + cells, DendriMACs® growing medium with supplements (GM-CSF, IL-4, IL-6, IL-1B, TNFa, PGE) was used. Immature Mo-DCs were loaded with autologous circulating tumor cell (CTCs) lysates. Autologous CTCs were sorted out by size-based filtration (MetaCell® ) of the leukapheresis CD14-negative fraction. A mixture of mature Mo-DCs and autologous non-target blood cells (NTBCs) was co-cultured and the activation effect of mature Mo-DCs on T-cell activation was monitored by means of multimarker gene expression profiling., Results: New protocols for mMo-DC production using automatization and CTC lysates were introduced including a feasible in vitro assay for mMo-DC efficacy evaluation. Gene expression analysis revealed elevation for following genes in NTBC (T cells) subset primed by mMo-DCs: CD8A, CD4, MKI67, MIF, TNFA, CD86, and CD80 (p ≤ 0.01)., Conclusion: Summarizing the presented data, we might conclude mMo-DCs were generated using CliniMACS Prodigy® machine and CTC lysates in a homogenous manner showing a potential to generate NTBC activation in co-cultures. Identification of the activation signals in T-cell population by simple multimarker-qPCRs could fasten the process of effective mMo-DC production., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2022
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25. Enrichment of circulating trophoblasts from maternal blood using filtration-based Metacell® technology.
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Weymaere J, Vander Plaetsen AS, Van Den Branden Y, Pospisilova E, Tytgat O, Deforce D, and Van Nieuwerburgh F
- Subjects
- DNA, Female, Fetus, Humans, Male, Pregnancy, Technology, Prenatal Diagnosis methods, Trophoblasts
- Abstract
In a cell-based non-invasive prenatal test (cbNIPT), intact circulating trophoblasts (CTs) are isolated from maternal blood for subsequent genetic analysis. Enrichment of these CTs from maternal blood is the most challenging step in the cbNIPT workflow. This study aims to assess the suitability of the filtration-based Metacell® technology to enrich CTs from maternal blood at week 10 to 13 of gestation. The Metacell® technology is a novel size-based enrichment technology that combines blood filtration through 8 μm pores with an in vitro culture method. Three protocols were evaluated. First, 8 mL or 16 mL of maternal blood was filtered and subsequently cultured in vitro on the separation membrane for 3 days in RPMI 1640. In addition, 16 mL of maternal blood was filtered, and immediately processed without further culturing. Y-chromosome-specific qPCR or STR analysis was performed to evaluate the enrichment of CTs. A total of 44 samples from pregnant women, out of which 26 were carrying a male fetus, were processed. Although five enriched male fetus samples show detectable male DNA quantities, it cannot be excluded that the obtained positive signal is caused by cell-free fetal DNA sticking to the Metacell® separation membrane. In conclusion, the Metacell® technology, tested as described, is not suitable for consistent enrichment of CTs., Competing Interests: We confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. All authors have approved the manuscript and agree with submission to PLOS ONE. The authors have declared that no competing interests exist.
- Published
- 2022
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26. Characterization of circulating tumor cells in early breast cancer patients receiving neoadjuvant chemotherapy.
- Author
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Jakabova A, Bielcikova Z, Pospisilova E, Petruzelka L, Blasiak P, Bobek V, and Kolostova K
- Abstract
Background and Aims: The aim of this study was to characterize circulating tumor cells (CTCs) during neoadjuvant chemotherapy (NACT) in early and locally advanced breast cancer (LABC) patients. Using ultrasound, tumor volume measurement was compared with the presence and the molecular nature of CTCs over multiple time intervals corresponding to treatment periods., Methods: A total of 20 patients diagnosed with breast cancer (BC) of different histotypes were monitored during the NACT period and in the follow-up period (~5 years). Peripheral blood for CTCs ( n = 115) was taken prior to NACT, after two to three chemotherapy cycles, after the completion of NACT (before surgery) and at some time points during adjuvant therapy. CTCs were enriched using a size-based filtration method (MetaCell®) capturing viable cells, which enabled vital fluorescence microscopy. A set of tumor-associated (TA) genes and chemoresistance-associated (CA) genes was analyzed by qPCR in the enriched CTC fractions., Results: The analysis of tumor volume reduction after administration of anthracyclines (AC) and taxanes (TAX) during NACT showed that AC therapy was responsive in 60% (12/20) of tumors, whereas TAX therapy was responsive in 30% (6/20; n.s.). After NACT, CTCs were still present in 70.5% (12/17) of patients (responders versus non-responders, 61.5% versus 100%; not significant).In triple-negative BC (TNBC) patients ( n = 8), tumor volume reduction was observed in 75% cases. CTCs were significantly reduced in 42.9% of all HER2-negative BC patients. In HER2+ tumors, CTC reduction was reported in 16.6% only. Relapses were also more prevalent in the HER2-positive patient group (28.5 versus 66.6%).During NACT, the presence of CTCs (three tests for each patient) identified patients with relapses and indicated significantly shorter progression-free survival (PFS) rates ( p = 0.03). Differentiation between progressive disease and non-progressive disease was obtained when the occurrence of excessive expression for CA genes in CTCs was compared ( p = 0.024). Absence of tumor volume reduction was also significantly indicative for progressive disease ( p = 0.0224).Disseminated CTCs in HER2-negative tumors expressed HER2 in 29% of samples collected during the overall follow-up period (16/55), and in 32% of samples during the follow-up of NACT (10/31). The change accounted for 78.5% of HER2-negative patients (11/14) in total, and 63.6% of the conversion cases occurred during NACT (7/11). For the remaining four patients (36.3%), conversion to HER2+ CTCs occurred later during adjuvant therapy. We believe there is the possibility of preventing further progression by identifying less responsive tumors during NACT using CTC monitoring, which could also be used effectively during adjuvant therapy., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)
- Published
- 2021
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27. Next generation sequencing of glioblastoma circulating tumor cells: non-invasive solution for disease monitoring.
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Kolostova K, Pospisilova E, Pavlickova V, Bartos R, Sames M, Pawlak I, and Bobek V
- Abstract
Treatment of aggressive glioblastoma multiforme (GBM) must be based on very precise histological and molecular diagnostic of GBM type. According to the WHO guidelines, only tissue biopsy is a relevant source of cellular material evaluated in the diagnostic process to specify the tumor features. Nevertheless, obtaining a GBM biopsy is complicated and relies mostly on resection surgery. Evaluating circulating free DNA and/or circulating tumor cells (CTCs) in the clinic, using a liquid biopsy could represent a non-invasive cancer care optimization. In the present study, the peripheral blood of patients undergoing GBM resection (n = 18) was collected and examined for CTCs. The feasibility of GBM molecular diagnostics from a simple non-invasive peripheral blood withdrawal was evaluated. The size-based enriched CTCs were analyzed using cytomorphology and their origin confirmed based on mutational analysis. In addition, shared DNA mutations in CTCs and in primary tumor tissue were searched. For the identification of CTCs, next generation sequencing (NGS) was used. The GeneReader™ sequencing platform enables targeted sequencing of a 12-gene panel and direct evaluation of detected gene variations using QIAGEN Clinical Insight Analyze (QCI-A) software with a special algorithm for liquid biopsy sequencing analysis. Herein, we present a standard operating procedure for CTC enrichment in GBM patients, CTC in vitro culture, CTC cytomorphological evaluation, and NGS analysis of CTCs using the QIAGEN Actionable Insights Tumor (ATP) Panel. CTCs were present in all tested patients (18/18). The NGS data generated for formalin-fixed paraffin-embedded (FFPE) primary tumor tissues and CTCs reached significantly high-quality parameters. The comparisons between different sample types (CTCs vs. primary tumors) and sampling area (different primary tumor regions) showed a significant level of concordance, indicating CTC testing could be used for patient monitoring and recurrence awareness. Notably, more mutations were detected when analyzing CTC samples compared with the paired primary tumors (n = 3). The results confirm the feasibility of using CTCs as a source of tumor DNA in a diagnostic process, especially when evaluating the molecular characteristics of GBMs. A major advantage of the presented NGS approach for detecting CTCs is the simultaneous identification of several markers relevant for GBM diagnostics, allowing molecular diagnostics on cytological specimens and potential administration of innovative targeted therapies., Competing Interests: None., (AJTR Copyright © 2021.)
- Published
- 2021
28. Detection of Circulating Tumor Cells in Renal Cell Carcinoma: Disease Stage Correlation and Molecular Characterization.
- Author
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Klezl P, Pospisilova E, Kolostova K, Sonsky J, Maly O, Grill R, Pawlak I, and Bobek V
- Abstract
The presence of circulating tumor cells (CTCs) in patients with solid tumors is associated with poor prognosis. However, there are limited data concerning the detection of CTCs in renal cell cancer (RCC). The aim of this study is to evaluate the presence of CTCs in peripheral blood of patients with RCC undergoing surgery (n = 186). CTCs were tested before and after surgery as well as during the follow-up period afterwards. In total 495 CTC testing in duplicates were provided. To enrich CTCs, a size-based separation protocol and tube MetaCell® was used. CTCs presence was evaluated by single cell cytomorphology based on vital fluorescence microscopy. Additionally, to standardly applied fluorescence stains, CTCs viability was controlled by mitochondrial activity. CTCs were detected independently on the sampling order in up to 86.7% of the tested blood samples in patients undergoing RCC surgery. There is higher probability of CTC detection with growing tumor size, especially in clear cell renal cell cancer (ccRCC) cases. Similarly, the tumor size corresponds with metastasis presence and lymph node positivity and CTC detection. This paper describes for the first-time successful analysis of viable CTCs and their mitochondria as a part of the functional characterization of CTCs in RCC.
- Published
- 2020
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29. Circulating Endometrial Cells in Women With Spontaneous Pneumothorax.
- Author
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Kiss I, Pospisilova E, Kolostova K, Maly V, Stanek I, Lischke R, Schutzner J, Pawlak I, and Bobek V
- Subjects
- Adult, CA-125 Antigen genetics, Case-Control Studies, Endometriosis genetics, Female, Humans, Keratin-18 genetics, Liquid Biopsy, Membrane Proteins genetics, Middle Aged, Mucin-1 genetics, Pleural Diseases genetics, Pneumothorax diagnosis, Pneumothorax genetics, Receptor, ErbB-2 genetics, Transcriptome, Vimentin genetics, Young Adult, Endometriosis blood, Endometrium cytology, Pleural Diseases blood, Pneumothorax blood
- Abstract
Background: The occurrence of catamenial pneumothorax (CP) is rare, and the awareness of this diagnosis among physicians is insufficient. CP is highly correlated with pelvic endometriosis and remains the most common form of thoracic endometriosis syndrome. Circulating endometrial cells (CECs) have been previously detected in patients with pelvic endometriosis. Could CECs bring new insights into pneumothorax management?, Methods: This study aims to describe the occurrence and molecular characteristics of CECs in women with spontaneous pneumothorax (SP) (N = 20) with high suspicion of its catamenial character. CECs were enriched from peripheral blood by size-based separation (MetaCell). In addition to cytomorphology, gene expression profiling of captured cells was performed for 24 endometriosis-associated genes., Results: CECs were present in all 20 patients with SP. Enriched CECs exhibited four character features: epithelial, stem cell-like, stroma-like, and glandular. However, not all of them were present in every sampling. Gene expression profiling revealed two distinct phenotypes of CECs in SP and/or CP: one of them refers to the diaphragm openings syndrome and the other to endometrial tissue pleural implantations. Comparisons of the gene expression profiles of CECs in pneumothorax (CECs-SP group) with CECs in pelvic endometriosis (CECs-non-SP group) have revealed significantly higher expression of HER2 in the CECs-SP group compared with the CECs-non-SP group., Conclusions: This proof-of-concept study demonstrates successful isolation and characterization of CECs in patients with SP. Identification of CECs in SP could alert endometriosis involvement and help early referral to gynecologic consultation for further examination and treatment., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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30. Circulating Endometrial Cells: A New Source of Information on Endometriosis Dynamics.
- Author
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Pospisilova E, Kiss I, Souckova H, Tomes P, Spicka J, Matkowski R, Jedryka M, Ferrero S, Bobek V, and Kolostova K
- Abstract
The focus of the presented work was to isolate and characterize circulating endometrial cells (CECs) enriched from peripheral blood (PB) of patients with diagnosed endometriosis. The molecular characteristics of CECs could be supportive for an understanding of endometriosis pathogenesis and treatment decisions in the future., Material and Methods: Blood samples ( n = 423) were tested for CECs presence. Subsequently, gene expression analysis (GEA) was carried out for CECs. In parallel, CECs presence and characteristics were tested during menstrual cycle (MC) phases in 11 patients. CECs were enriched by size-based separation., Results: CECs were present in 78.4% of the tested blood samples. In line with the revised American Fertility Society (rAFS) classification, CECs presence was confirmed in all the acknowledged endometriosis stages: minimal, mild, moderate, and severe. Surprisingly, CECs negativity rate was also reported for severe disease in 21.1% of cases. The CECs captured during MC phases displayed different cytomorphology, including epithelial, stromal, and stem cell-like characteristics. The highest CECs numbers were detected in the mid-secretory phase of MC, which corresponds to uterine lining decidualization. CECs captured during mid-secretory periods expressed genes KRT18 , NANOG , and VIM in higher amounts when compared to the proliferative phase of MC, where genes KRT19 and ESR1 were mostly elevated. GEA of the super-positive CECs samples (1000 CECs/8 mL PB) revealed high expression of genes KRT18 , VIM , NANOG , and FLT1 . The expression of these genes was also elevated in the endometriosis tissue samples and endometrioma., Conclusion: The panel of the identified CEC genes could be tested in a prospective manner to confirm the role of CECs in endometriosis pathogenesis and diagnostics.
- Published
- 2019
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31. Molecular characterization and heterogeneity of circulating tumor cells in breast cancer.
- Author
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Jakabova A, Bielcikova Z, Pospisilova E, Matkowski R, Szynglarewicz B, Staszek-Szewczyk U, Zemanova M, Petruzelka L, Eliasova P, Kolostova K, and Bobek V
- Subjects
- Adult, Aged, Breast Neoplasms genetics, Breast Neoplasms pathology, Estrogen Receptor alpha genetics, Female, Gene Expression Regulation, Neoplastic, Humans, Middle Aged, Neoplasm Staging, Receptor, ErbB-2 genetics, Biomarkers, Tumor genetics, Breast Neoplasms blood, Genetic Heterogeneity, Neoplastic Cells, Circulating pathology
- Abstract
Introduction: This study analyzes peripheral blood samples from breast cancer (BC) patients. CTCs from peripheral blood were enriched by size-based separation and were then cultivated in vitro. The primary aim of this study was to demonstrate the antigen independent CTC separation method with high CTC recovery. Subsequently, CTCs enriched several times during the treatment were characterized molecularly., Methods: Patients with different stages of BC (N = 167) were included into the study. All patients were candidates for surgery, surgical diagnostics, or were undergoing chemotherapy. In parallel, 20 patients were monitored regularly and in addition to CTC presence, also CTC character was examined by qPCR, with special focus on HER2 and ESR status., Results: CTC positivity in the cohort was 76%. There was no significant difference between the tested groups, but the highest CTC occurrence was identified in the group undergoing surgery and similarly in the group before the start of neoadjuvant treatment. On the other hand, the lowest CTC frequencies were observed in the menopausal patient group (56%), ESR+ patient group (60%), and DCIS group (44.4%). It is worth noting that after completion of neoadjuvant therapy (NACT) CTCs were present in 77.7% of cases. On the other hand, patients under hormonal treatment were CTC positive only in 52% of cases., Discussions: Interestingly, HER2 and ESR status of CTCs differs from the status of primary tumor. In 50% of patients HER2 status on CTCs changed not only from HER2+ to HER2-, but also from HER2- to HER2+ (33%). ESR status in CTCs changed only in one direction from ESR+ to ESR-., Conclusions: Data obtained from the present study suggest that BC is a heterogeneous disease but CTCs may be detected independently of the disease characteristics in 76% of patients at any time point during the course of the disease. This relatively high CTC occurrence in BC should be considered when planning the long-term patient monitoring.
- Published
- 2017
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32. Molecular characterization of circulating tumor cells in ovarian cancer.
- Author
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Kolostova K, Pinkas M, Jakabova A, Pospisilova E, Svobodova P, Spicka J, Cegan M, Matkowski R, and Bobek V
- Abstract
The main focus of the study was to detect circulating tumor cells (CTCs) in ovarian cancer (OC) patients using a new methodological approach (MetaCell(TM)) which is based on size-dependent separation of CTCs and subsequent cytomorphological evaluation. Cytomorphological evaluation using vital fluorescence microscopy approach enables to use the captured cells for further RNA/DNA analysis. The cytomorphological analysis is then completed by gene expression analysis (GEA). GEA showed that relative expression of EPCAM is elevated in CTC-enriched fractions in comparison to the whole peripheral blood sample and that the expression grows with in vitro cultivation time. Comparison of the relative gene expression level in the group of peripheral blood samples and CTC-fraction samples confirmed a statistically significant difference for the following genes (p < 0.02): KRT7, WT1, EPCAM, MUC16, MUC1, KRT18 and KRT19. Thus, we suggest that the combination of the above listed genes could confirm CTCs presence in OC patients with higher specificity than when GEA tests are performed for one marker only. The GEA revealed two separate clusters identifying patients with or without CTCs.
- Published
- 2016
33. Calcium influx rescues adenylate cyclase-hemolysin from rapid cell membrane removal and enables phagocyte permeabilization by toxin pores.
- Author
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Fiser R, Masin J, Bumba L, Pospisilova E, Fayolle C, Basler M, Sadilkova L, Adkins I, Kamanova J, Cerny J, Konopasek I, Osicka R, Leclerc C, and Sebo P
- Subjects
- Animals, Cell Line, Clathrin metabolism, Endocytosis drug effects, Ion Transport drug effects, Macrophages cytology, Mice, Adenylate Cyclase Toxin pharmacology, Cell Membrane Permeability drug effects, Macrophages metabolism, Membrane Microdomains metabolism, Potassium metabolism
- Abstract
Bordetella adenylate cyclase toxin-hemolysin (CyaA) penetrates the cytoplasmic membrane of phagocytes and employs two distinct conformers to exert its multiple activities. One conformer forms cation-selective pores that permeabilize phagocyte membrane for efflux of cytosolic potassium. The other conformer conducts extracellular calcium ions across cytoplasmic membrane of cells, relocates into lipid rafts, translocates the adenylate cyclase enzyme (AC) domain into cells and converts cytosolic ATP to cAMP. We show that the calcium-conducting activity of CyaA controls the path and kinetics of endocytic removal of toxin pores from phagocyte membrane. The enzymatically inactive but calcium-conducting CyaA-AC⁻ toxoid was endocytosed via a clathrin-dependent pathway. In contrast, a doubly mutated (E570K+E581P) toxoid, unable to conduct Ca²⁺ into cells, was rapidly internalized by membrane macropinocytosis, unless rescued by Ca²⁺ influx promoted in trans by ionomycin or intact toxoid. Moreover, a fully pore-forming CyaA-ΔAC hemolysin failed to permeabilize phagocytes, unless endocytic removal of its pores from cell membrane was decelerated through Ca²⁺ influx promoted by molecules locked in a Ca²⁺-conducting conformation by the 3D1 antibody. Inhibition of endocytosis also enabled the native B. pertussis-produced CyaA to induce lysis of J774A.1 macrophages at concentrations starting from 100 ng/ml. Hence, by mediating calcium influx into cells, the translocating conformer of CyaA controls the removal of bystander toxin pores from phagocyte membrane. This triggers a positive feedback loop of exacerbated cell permeabilization, where the efflux of cellular potassium yields further decreased toxin pore removal from cell membrane and this further enhances cell permeabilization and potassium efflux.
- Published
- 2012
- Full Text
- View/download PDF
34. Inflammasome activation by adenylate cyclase toxin directs Th17 responses and protection against Bordetella pertussis.
- Author
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Dunne A, Ross PJ, Pospisilova E, Masin J, Meaney A, Sutton CE, Iwakura Y, Tschopp J, Sebo P, and Mills KH
- Subjects
- Adenylate Cyclase Toxin toxicity, Animals, CD4-Positive T-Lymphocytes enzymology, CD4-Positive T-Lymphocytes microbiology, Carrier Proteins metabolism, Caspase 1 metabolism, Cell Polarity immunology, Cells, Cultured, Epitopes, T-Lymphocyte immunology, Inflammation enzymology, Inflammation microbiology, Inflammation prevention & control, Inflammation Mediators physiology, Interleukin-17 deficiency, Interleukin-17 physiology, Interleukin-1beta biosynthesis, Interleukin-1beta physiology, Intubation, Intratracheal, Mice, Mice, Inbred C57BL, Mice, Knockout, NLR Family, Pyrin Domain-Containing 3 Protein, Respiratory Tract Infections enzymology, Respiratory Tract Infections microbiology, Respiratory Tract Infections pathology, Adenylate Cyclase Toxin physiology, Bordetella pertussis immunology, CD4-Positive T-Lymphocytes immunology, Inflammation Mediators metabolism, Interleukin-17 biosynthesis, Respiratory Tract Infections prevention & control
- Abstract
Inflammasome-mediated IL-1beta production is central to the innate immune defects that give rise to certain autoinflammatory diseases and may also be associated with the generation of IL-17-producing CD4(+) T (Th17) cells that mediate autoimmunity. However, the role of the inflammasome in driving adaptive immunity to infection has not been addressed. In this article, we demonstrate that inflammasome-mediated IL-1beta plays a critical role in promoting Ag-specific Th17 cells and in generating protective immunity against Bordetella pertussis infection. Using a murine respiratory challenge model, we demonstrated that the course of B. pertussis infection was significantly exacerbated in IL-1R type I-defective (IL-1RI(-/-)) mice. We found that adenylate cyclase toxin (CyaA), a key virulence factor secreted by B. pertussis, induced robust IL-1beta production by dendritic cells through activation of caspase-1 and the NALP3-containing inflammasome complex. Using mutant toxins, we demonstrate that CyaA-mediated activation of caspase-1 was not dependent on adenylate cyclase enzyme activity but was dependent on the pore-forming capacity of CyaA. In addition, CyaA promoted the induction of Ag-specific Th17 cells in wild-type but not IL-1RI(-/-) mice. Furthermore, the bacterial load was enhanced in IL-17-defective mice. Our findings demonstrate that CyaA, a virulence factor from B. pertussis, promotes innate IL-1beta production via activation of the NALP3 inflammasome and, thereby, polarizes T cell responses toward the Th17 subtype. In addition to its known role in subverting host immunity, our findings suggest that CyaA can promote IL-1beta-mediated Th17 cells, which promote clearance of the bacteria from the respiratory tract.
- Published
- 2010
- Full Text
- View/download PDF
35. Adenylate cyclase toxin translocates across target cell membrane without forming a pore.
- Author
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Osickova A, Masin J, Fayolle C, Krusek J, Basler M, Pospisilova E, Leclerc C, Osicka R, and Sebo P
- Subjects
- Adenylate Cyclase Toxin genetics, Amino Acid Substitution, Animals, Cells, Cultured, Dendritic Cells immunology, Epitopes, T-Lymphocyte immunology, Macrophages immunology, Mice, Models, Biological, Monocytes immunology, Mutagenesis, Site-Directed, Mutant Proteins genetics, Mutant Proteins metabolism, Ovalbumin immunology, Protein Transport, T-Lymphocytes, Cytotoxic immunology, Adenylate Cyclase Toxin metabolism, Cell Membrane metabolism
- Abstract
The adenylate cyclase toxin-haemolysin of Bordetella (CyaA) targets CD11b(+) myeloid phagocytes and translocates across their cytoplasmic membrane an adenylate cyclase (AC) enzyme that catalyses conversion of cytosolic ATP into cAMP. In parallel, CyaA acts as a cytolysin forming cation-selective pores, which permeabilize cell membrane and eventually provoke cell lysis. Using cytolytic activity, potassium efflux and patch-clamp assays, we show that a combination of substitutions within the pore-forming (E570Q) and acylation-bearing domain (K860R) ablates selectively the cell-permeabilizing activity of CyaA. At the same time, however, the capacity of such mutant CyaA to translocate the AC domain across cytoplasmic membrane into cytosol of macrophage cells and to elevate cellular cAMP concentrations remained intact. Moreover, the combination of E570Q+K860R substitutions suppressed the residual cytolytic activity of the enzymatically inactive CyaA/OVA/AC(-) toxoid on CD11b-expressing monocytes, while leaving unaffected the capacity of the mutant toxoid to deliver in vitro a reporter CD8(+) T cell epitope from ovalbumin (OVA) to the cytosolic pathway of dendritic cells for MHC class I-restricted presentation and induce in vivo an OVA-specific cytotoxic T cell response. CyaA, hence, employs a mechanism of AC enzyme domain translocation across cellular membrane that avoids passage across the cytolytic pore formed by toxin oligomers.
- Published
- 2010
- Full Text
- View/download PDF
36. Post-operative pain behavior in rats is reduced after single high-concentration capsaicin application.
- Author
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Pospisilova E and Palecek J
- Subjects
- Animals, Behavior, Animal drug effects, Disease Models, Animal, Male, Nociceptors drug effects, Rats, Rats, Wistar, Capsaicin administration & dosage, Nociceptors metabolism, Pain Measurement drug effects, Pain Threshold drug effects, Pain, Postoperative metabolism, Pain, Postoperative prevention & control, TRPV Cation Channels metabolism
- Abstract
Surgical procedures associated with tissue injury are often followed by increased sensitivity to innocuous and noxious stimuli in the vicinity of the surgical wound. The aim of this study was to evaluate the role of transient receptor potential vanilloid 1 receptor (TRPV1) containing nociceptors in this process, by their functional inactivation using a high-concentration intradermal injection of capsaicin in a rat plantar incision model. Paw withdrawal responses to mechanical stimuli (von Frey filaments 10-367mN) and to radiant heat applied on plantar skin were tested in animals treated with capsaicin or the vehicle 6 days and 24h before or 2h after the incision was made. In the vehicle-treated animals, mechanical and thermal sensitivity increased significantly 1-96h following the incision. Capsaicin applied 24h before the surgery was most effective and significantly diminished the development of post-incisional mechanical allodynia and hyperalgesia. Thermal hypoalgesia was present in the incised paw after the capsaicin treatment. Capsaicin application 6 days before the incision induced thermal hypoalgesia before the incision but did not prevent completely the thermal hyperalgesia after the incision, while there was also a reduction of mechanical hypersensitivity. Application of the capsaicin injection after the incision showed its first effect at 2h after the injection and at 24h the effect was comparable with the 6 days pretreatment. Our results show an important role of TRPV1-containing nociceptors in the development of post-surgical hypersensitivity and suggest that local, high-concentration capsaicin treatment could be used to reduce it.
- Published
- 2006
- Full Text
- View/download PDF
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