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53. NEUROPSYCHOLOGY

Author

Boman, K. K., primary, Hornquist, L., additional, Rickardsson, J., additional, Lannering, B., additional, Gustafsson, G., additional, Pitchford, N., additional, Davis, E., additional, Walker, D., additional, Hoang, D. H., additional, Pagnier, A., additional, Cousin, E., additional, Guichardet, K., additional, Schiff, I., additional, Dubois-Teklali, F., additional, Krainik, A., additional, Lazar, M. B., additional, Resnik, K., additional, Olsson, I. T., additional, Perrin, S., additional, Burtscher, I. B., additional, Lundgren, J., additional, Kahn, A., additional, Johanson, A., additional, Korzeniewska, J., additional, Dembowska-Baginska, B., additional, Perek-Polnik, M., additional, Walsh, K., additional, Gioia, A., additional, Wells, E., additional, Packer, R., additional, de Speville, E. D., additional, Dufour, C., additional, Bolle, S., additional, Giraudat, K., additional, Longaud, A., additional, Kieffer, V., additional, Grill, J., additional, Puget, S., additional, Valteau-Couanet, D., additional, Hetz-Pannier, L., additional, Noulhiane, M., additional, Chieffo, D., additional, Tamburrini, G., additional, Caldarelli, M., additional, Di Rocco, C., additional, Margelisch, K., additional, Studer, M., additional, Steinlin, M., additional, Leibundgut, K., additional, Heinks, T., additional, Longaud-Vales, A., additional, Chevignard, M., additional, Pujet, S., additional, Sainte-Rose, C., additional, Dellatolas, G., additional, Kahalley, L., additional, Grosshans, D., additional, Paulino, A., additional, Ris, M. D., additional, Chintagumpala, M., additional, Okcu, F., additional, Moore, B., additional, Stancel, H., additional, Minard, C., additional, Guffey, D., additional, Mahajan, A., additional, Herrington, B., additional, Raiker, J., additional, Manning, E., additional, Criddle, J., additional, Karlson, C., additional, Guerry, W., additional, Finlay, J., additional, Sands, S., additional, Dockstader, C., additional, Skocic, J., additional, Bouffet, E., additional, Laughlin, S., additional, Tabori, U., additional, Mabbott, D., additional, Moxon-Emre, I., additional, Scantlebury, N., additional, Taylor, M. D., additional, Malkin, D., additional, Law, N., additional, Kumabe, T., additional, Leonard, J., additional, Rubin, J., additional, Jung, S., additional, Kim, S.-K., additional, Gupta, N., additional, Weiss, W., additional, Faria, C., additional, Vibhakar, R., additional, Spiegler, B., additional, Janzen, L., additional, Liu, F., additional, Decker, L., additional, Lemiere, J., additional, Vercruysse, T., additional, Haers, M., additional, Vandenabeele, K., additional, Geuens, S., additional, Jacobs, S., additional, Van Gool, S., additional, Riggs, L., additional, Piscione, J., additional, Timmons, B., additional, Cunningham, T., additional, Bartels, U., additional, Chakravarty, M., additional, Laperriere, N., additional, Pipitone, J., additional, Strother, D., additional, Hukin, J., additional, Fryer, C., additional, McConnell, D., additional, Secco, D. E., additional, Cappelletti, S., additional, Gentile, S., additional, Cacchione, A., additional, Del Bufalo, F., additional, Staccioli, S., additional, Spagnoli, A., additional, Messina, R., additional, Carai, A., additional, Marras, C. E., additional, Mastronuzzi, A., additional, Brinkman, T., additional, Armstrong, G., additional, Kimberg, C., additional, Gajjar, A., additional, Srivastava, D. K., additional, Robison, L., additional, Hudson, M., additional, Krull, K., additional, Hardy, K., additional, Hostetter, S., additional, Hwang, E., additional, Leiss, U., additional, Bemmer, A., additional, Pletschko, T., additional, Grafeneder, J., additional, Schwarzinger, A., additional, Deimann, P., additional, Slavc, I., additional, Batchelder, P., additional, Wilkening, G., additional, Hankinson, T., additional, Foreman, N., additional, and Handler, M., additional

Published
2014
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54. HIGH GRADE GLIOMAS AND DIPG

Author

Classen, C. F., primary, William, D., additional, Linnebacher, M., additional, Farhod, A., additional, Kedr, W., additional, Elsabe, B., additional, Fadel, S., additional, Van Gool, S., additional, De Vleeschouwer, S., additional, Koks, C., additional, Garg, A., additional, Ehrhardt, M., additional, Riva, M., additional, Agostinis, P., additional, Graf, N., additional, Yao, T.-W., additional, Yoshida, Y., additional, Zhang, J., additional, Ozawa, T., additional, James, D., additional, Nicolaides, T., additional, Kebudi, R., additional, Cakir, F. B., additional, Gorgun, O., additional, Agaoglu, F. Y., additional, Darendeliler, E., additional, Al-Kofide, A., additional, Al-Shail, E., additional, Khafaga, Y., additional, Al-Hindi, H., additional, Dababo, M., additional, Haq, A. U., additional, Anas, M., additional, Barria, M. G., additional, Siddiqui, K., additional, Hassounah, M., additional, Ayas, M., additional, van Zanten, S. V., additional, Jansen, M., additional, van Vuurden, D., additional, Huisman, M., additional, Vugts, D., additional, Hoekstra, O., additional, van Dongen, G., additional, Kaspers, G., additional, Cockle, J., additional, Ilett, E., additional, Scott, K., additional, Bruning-Richardson, A., additional, Picton, S., additional, Short, S., additional, Melcher, A., additional, Benesch, M., additional, Warmuth-Metz, M., additional, von Bueren, A. O., additional, Hoffmann, M., additional, Pietsch, T., additional, Kortmann, R.-D., additional, Eyrich, M., additional, Rutkowski, S., additional, Fruhwald, M. C., additional, Faber, J., additional, Kramm, C., additional, Porkholm, M., additional, Valanne, L., additional, Lonnqvist, T., additional, Holm, S., additional, Lannering, B., additional, Riikonen, P., additional, Wojcik, D., additional, Sehested, A., additional, Clausen, N., additional, Harila-Saari, A., additional, Schomerus, E., additional, Thorarinsdottir, H. K., additional, Lahteenmaki, P., additional, Arola, M., additional, Thomassen, H., additional, Saarinen-Pihkala, U. M., additional, Kivivuori, S.-M., additional, Buczkowicz, P., additional, Hoeman, C., additional, Rakopoulos, P., additional, Pajovic, S., additional, Morrison, A., additional, Bouffet, E., additional, Bartels, U., additional, Becher, O., additional, Hawkins, C., additional, Gould, T. W. A., additional, Rahman, C. V., additional, Smith, S. J., additional, Barrett, D. A., additional, Shakesheff, K. M., additional, Grundy, R. G., additional, Rahman, R., additional, Barua, N., additional, Cronin, D., additional, Gill, S., additional, Lowisl, S., additional, Hochart, A., additional, Maurage, C.-A., additional, Rocourt, N., additional, Vinchon, M., additional, Kerdraon, O., additional, Escande, F., additional, Grill, J., additional, Pick, V. K., additional, Leblond, P., additional, Burzynski, G., additional, Janicki, T., additional, Burzynski, S., additional, Marszalek, A., additional, Ramani, N., additional, Zaky, W., additional, Kannan, G., additional, Morani, A., additional, Sandberg, D., additional, Ketonen, L., additional, Maher, O., additional, Corrales-Medina, F., additional, Meador, H., additional, Khatua, S., additional, Brassesco, M., additional, Delsin, L., additional, Roberto, G., additional, Silva, C., additional, Ana, L., additional, Rego, E., additional, Scrideli, C., additional, Umezawa, K., additional, Tone, L., additional, Kim, S. J., additional, Kim, C.-Y., additional, Kim, I.-A., additional, Han, J. H., additional, Choi, B.-S., additional, Ahn, H. S., additional, Choi, H. S., additional, Haque, F., additional, Layfield, R., additional, Grundy, R., additional, Gandola, L., additional, Pecori, E., additional, Biassoni, V., additional, Schiavello, E., additional, Chiruzzi, C., additional, Spreafico, F., additional, Modena, P., additional, Bach, F., additional, Pignoli, E., additional, Massimino, M., additional, Drogosiewicz, M., additional, Dembowska-Baginska, B., additional, Jurkiewicz, E., additional, Filipek, I., additional, Perek-Polnik, M., additional, Swieszkowska, E., additional, Perek, D., additional, Bender, S., additional, Jones, D. T., additional, Warnatz, H.-J., additional, Hutter, B., additional, Zichner, T., additional, Gronych, J., additional, Korshunov, A., additional, Eils, R., additional, Korbel, J. O., additional, Yaspo, M.-L., additional, Lichter, P., additional, Pfister, S. M., additional, Yadavilli, S., additional, Becher, O. J., additional, Kambhampati, M., additional, Packer, R. J., additional, Nazarian, J., additional, Lechon, F. C., additional, Fowkes, L., additional, Khabra, K., additional, Martin-Retortillo, L. M., additional, Marshall, L. V., additional, Vaidya, S., additional, Koh, D.-M., additional, Leach, M. O., additional, Pearson, A. D., additional, Zacharoulis, S., additional, Schrey, D., additional, Barone, G., additional, Panditharatna, E., additional, Stampar, M., additional, Siu, A., additional, Gordish-Dressman, H., additional, Devaney, J., additional, Hwang, E. I., additional, Chung, A. H., additional, Mittapalli, R. K., additional, Elmquist, W. F., additional, Castel, D., additional, Debily, M.-A., additional, Philippe, C., additional, Truffaux, N., additional, Taylor, K., additional, Calmon, R., additional, Boddaert, N., additional, Le Dret, L., additional, Saulnier, P., additional, Lacroix, L., additional, Mackay, A., additional, Jones, C., additional, Puget, S., additional, Sainte-Rose, C., additional, Blauwblomme, T., additional, Varlet, P., additional, Entz-Werle, N., additional, Maugard, C., additional, Bougeard, G., additional, Nguyen, A., additional, Chenard, M. P., additional, Schneider, A., additional, Gaub, M. P., additional, Tsoli, M., additional, Vanniasinghe, A., additional, Luk, P., additional, Dilda, P., additional, Haber, M., additional, Hogg, P., additional, Ziegler, D., additional, Simon, S., additional, Monje, M., additional, Gurova, K., additional, Gudkov, A., additional, Zapotocky, M., additional, Churackova, M., additional, Malinova, B., additional, Zamecnik, J., additional, Kyncl, M., additional, Tichy, M., additional, Puchmajerova, A., additional, Stary, J., additional, Sumerauer, D., additional, Boult, J., additional, Vinci, M., additional, Perryman, L., additional, Box, G., additional, Jury, A., additional, Popov, S., additional, Ingram, W., additional, Eccles, S., additional, Robinson, S., additional, Emir, S., additional, Demir, H. A., additional, Bayram, C., additional, Cetindag, F., additional, Kabacam, G. B., additional, Fettah, A., additional, Li, J., additional, Jamin, Y., additional, Cummings, C., additional, Bamber, J., additional, Sinkus, R., additional, Nandhabalan, M., additional, Bjerke, L., additional, Burford, A., additional, von Bueren, A., additional, Baudis, M., additional, Clarke, P., additional, Collins, I., additional, Workman, P., additional, Olaciregui, N., additional, Mora, J., additional, Carcaboso, A., additional, Bullock, A., additional, Alonso, M., additional, de Torres, C., additional, Cruz, O., additional, Pencreach, E., additional, Moussalieh, F. M., additional, Guenot, D., additional, Namer, I., additional, Pollack, I., additional, Jakacki, R., additional, Butterfield, L., additional, Hamilton, R., additional, Panigrahy, A., additional, Potter, D., additional, Connelly, A., additional, Dibridge, S., additional, Whiteside, T., additional, Okada, H., additional, Ahsan, S., additional, Raabe, E., additional, Haffner, M., additional, Warren, K., additional, Quezado, M., additional, Ballester, L., additional, Eberhart, C., additional, Rodriguez, F., additional, Ramachandran, C., additional, Nair, S., additional, Quirrin, K.-W., additional, Khatib, Z., additional, Escalon, E., additional, Melnick, S., additional, Classen, C. F., additional, Hofmann, M., additional, Schmid, I., additional, Simon, T., additional, Maass, E., additional, Russo, A., additional, Fleischhack, G., additional, Becker, M., additional, Hauch, H., additional, Sander, A., additional, Grasso, C., additional, Berlow, N., additional, Liu, L., additional, Davis, L., additional, Huang, E., additional, Woo, P., additional, Tang, Y., additional, Ponnuswami, A., additional, Chen, S., additional, Huang, Y., additional, Hutt-Cabezas, M., additional, Dret, L., additional, Meltzer, P., additional, Mao, H., additional, Abraham, J., additional, Fouladi, M., additional, Svalina, M. N., additional, Wang, N., additional, Hulleman, E., additional, Li, X.-N., additional, Keller, C., additional, Spellman, P. T., additional, Pal, R., additional, Jansen, M. H. A., additional, Sewing, A. C. P., additional, Lagerweij, T., additional, Vuchts, D. J., additional, van Vuurden, D. G., additional, Caretti, V., additional, Wesseling, P., additional, Kaspers, G. J. L., additional, Cohen, K., additional, Pearl, M., additional, Kogiso, M., additional, Zhang, L., additional, Qi, L., additional, Lindsay, H., additional, Lin, F., additional, Berg, S., additional, Muscal, J., additional, Amayiri, N., additional, Tabori, U., additional, Campbel, B., additional, Bakry, D., additional, Aronson, M., additional, Durno, C., additional, Gallinger, S., additional, Malkin, D., additional, Qaddumi, I., additional, Musharbash, A., additional, Swaidan, M., additional, Al-Hussaini, M., additional, Shandilya, S., additional, McCully, C., additional, Murphy, R., additional, Akshintala, S., additional, Cole, D., additional, Macallister, R. P., additional, Cruz, R., additional, Widemann, B., additional, Salloum, R., additional, Smith, A., additional, Glaunert, M., additional, Ramkissoon, A., additional, Peterson, S., additional, Baker, S., additional, Chow, L., additional, Sandgren, J., additional, Pfeifer, S., additional, Popova, S., additional, Alafuzoff, I., additional, de Stahl, T. D., additional, Pietschmann, S., additional, Kerber, M. J., additional, Zwiener, I., additional, Henke, G., additional, Muller, K., additional, Sieow, N. Y.-F., additional, Hoe, R. H. M., additional, Tan, A. M., additional, Chan, M. Y., additional, Soh, S. Y., additional, Burrell, K., additional, Chornenkyy, Y., additional, Remke, M., additional, Golbourn, B., additional, Barzczyk, M., additional, Taylor, M., additional, Rutka, J., additional, Dirks, P., additional, Zadeh, G., additional, Agnihotri, S., additional, Hashizume, R., additional, Ihara, Y., additional, Andor, N., additional, Chen, X., additional, Lerner, R., additional, Huang, X., additional, Tom, M., additional, Solomon, D., additional, Mueller, S., additional, Petritsch, C., additional, Zhang, Z., additional, Gupta, N., additional, Waldman, T., additional, Dujua, A., additional, Co, J., additional, Hernandez, F., additional, Doromal, D., additional, Hegde, M., additional, Wakefield, A., additional, Brawley, V., additional, Grada, Z., additional, Byrd, T., additional, Chow, K., additional, Krebs, S., additional, Heslop, H., additional, Gottschalk, S., additional, Yvon, E., additional, Ahmed, N., additional, Cornilleau, G., additional, Paulsson, J., additional, Andreiuolo, F., additional, Guerrini-Rousseau, L., additional, Geoerger, B., additional, Vassal, G., additional, Ostman, A., additional, Parsons, D. W., additional, Trevino, L. R., additional, Gao, F., additional, Shen, X., additional, Hampton, O., additional, Kosigo, M., additional, Baxter, P. A., additional, Su, J. M., additional, Chintagumpala, M., additional, Dauser, R., additional, Adesina, A., additional, Plon, S. E., additional, Wheeler, D. A., additional, Lau, C. C., additional, Gielen, G., additional, Muehlen, A. z., additional, Kwiecien, R., additional, Wolff, J., additional, Lulla, R. R., additional, Laskowski, J., additional, Goldman, S., additional, Gopalakrishnan, V., additional, Fangusaro, J., additional, Kieran, M., additional, Fontebasso, A., additional, Papillon-Cavanagh, S., additional, Schwartzentruber, J., additional, Nikbakht, H., additional, Gerges, N., additional, Fiset, P.-O., additional, Bechet, D., additional, Faury, D., additional, De Jay, N., additional, Ramkissoon, L., additional, Corcoran, A., additional, Jones, D., additional, Sturm, D., additional, Johann, P., additional, Tomita, T., additional, Nagib, M., additional, Bendel, A., additional, Goumnerova, L., additional, Bowers, D. C., additional, Leonard, J. R., additional, Rubin, J. B., additional, Alden, T., additional, DiPatri, A., additional, Browd, S., additional, Leary, S., additional, Jallo, G., additional, Prados, M. D., additional, Banerjee, A., additional, Carret, A.-S., additional, Ellezam, B., additional, Crevier, L., additional, Klekner, A., additional, Bognar, L., additional, Hauser, P., additional, Garami, M., additional, Myseros, J., additional, Dong, Z., additional, Siegel, P. M., additional, Gump, W., additional, Ayyanar, K., additional, Ragheb, J., additional, Krieger, M., additional, Kiehna, E., additional, Robison, N., additional, Harter, D., additional, Gardner, S., additional, Handler, M., additional, Foreman, N., additional, Brahma, B., additional, MacDonald, T., additional, Malkin, H., additional, Chi, S., additional, Manley, P., additional, Bandopadhayay, P., additional, Greenspan, L., additional, Ligon, A., additional, Albrecht, S., additional, Ligon, K. L., additional, Majewski, J., additional, Jabado, N., additional, Cordero, F., additional, Halvorson, K., additional, Taylor, I., additional, Hutt, M., additional, Weingart, M., additional, Price, A., additional, Kantar, M., additional, Onen, S., additional, Kamer, S., additional, Turhan, T., additional, Kitis, O., additional, Ertan, Y., additional, Cetingul, N., additional, Anacak, Y., additional, Akalin, T., additional, Ersahin, Y., additional, Mason, G., additional, Ho, C., additional, Crozier, F., additional, Vezina, G., additional, Packer, R., additional, Hwang, E., additional, Gilheeney, S., additional, Millard, N., additional, DeBraganca, K., additional, Khakoo, Y., additional, Kramer, K., additional, Wolden, S., additional, Donzelli, M., additional, Fischer, C., additional, Petriccione, M., additional, Dunkel, I., additional, Afzal, S., additional, Fleming, A., additional, Larouche, V., additional, Zelcer, S., additional, Johnston, D. L., additional, Kostova, M., additional, Mpofu, C., additional, Decarie, J.-C., additional, Strother, D., additional, Lafay-Cousin, L., additional, Eisenstat, D., additional, Fryer, C., additional, Hukin, J., additional, Hsu, M., additional, Lasky, J., additional, Moore, T., additional, Liau, L., additional, Davidson, T., additional, Prins, R., additional, Hassal, T., additional, Baugh, J., additional, Kirkendall, J., additional, Doughman, R., additional, Leach, J., additional, Jones, B., additional, Miles, L., additional, Hargrave, D., additional, Jacques, T., additional, Savage, S., additional, Saunders, D., additional, Wallace, R., additional, Flutter, B., additional, Morgenestern, D., additional, Blanco, E., additional, Howe, K., additional, Lowdell, M., additional, Samuel, E., additional, Michalski, A., additional, Anderson, J., additional, Arakawa, Y., additional, Umeda, K., additional, Watanabe, K.-i., additional, Mizowaki, T., additional, Hiraoka, M., additional, Hiramatsu, H., additional, Adachi, S., additional, Kunieda, T., additional, Takagi, Y., additional, Miyamoto, S., additional, Venneti, S., additional, Santi, M., additional, Felicella, M. M., additional, Sullivan, L. M., additional, Dolgalev, I., additional, Martinez, D., additional, Perry, A., additional, Lewis, P. W., additional, Allis, D. C., additional, Thompson, C. B., additional, and Judkins, A. R., additional

Published
2014
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55. Interaction of CTLA‐4 (CD152) with CD80 or CD86 inhibits human T‐cell activation

Author

Vandenborre, K, Van Gool, S W, Kasran, A, Ceuppens, J L, Boogaerts, M A, and Vandenberghe, P

Subjects
Immunoconjugates, Membrane Glycoproteins, T-Lymphocytes, Antibodies, Monoclonal, hemic and immune systems, chemical and pharmacologic phenomena, Cytotoxicity Tests, Immunologic, Lymphocyte Activation, Antigens, Differentiation, biological factors, Abatacept, CD28 Antigens, Antigens, CD, B7-1 Antigen, Humans, Original Article, CTLA-4 Antigen, B7-2 Antigen
Abstract

Occupancy of CTLA-4 (cytotoxic T-lymphocyte antigen-4 or CD152) negatively regulates the activation of mouse T lymphocytes, as indicated by the fate of CTLA-4-deficient mice, by the impact of anti-CTLA-4 monoclonal antibodies (mAbs) on mouse T-cell activation in vitro and by the impact of CTLA-4 blockade on the course of experimental tumoral, autoimmune, alloimmune or infectious disease in this animal. The function of human CTLA-4, however, remains less clear. The expression and function of human CTLA-4 were further explored. CTLA-4 was expressed under mitogenic conditions only, its expression being, at least partially, dependent on the secretion of interleukin-2. Memory T cells expressed CTLA-4 with faster kinetics than naive T cells. The functional role of human CTLA-4 was assessed utilizing a panel of four anti-CTLA-4 mAbs that blocked the interaction between CTLA-4 and its ligands. These mAbs, in immobilized form, profoundly inhibited the activation of T cells by immobilized anti-CD3 mAb in the absence of anti-CD28 mAb, but co-stimulated T-cell activation in the presence of anti-CD28 mAb. Finally, and importantly, blockade of the interaction of CTLA-4 with its ligands using soluble anti-CTLA-4 mAbs, in intact form or as Fab fragments, enhanced T-cell activation in several polyclonal or alloantigen-specific CD80- or CD80/CD86-dependent assays, as measured by cytokine production, cellular proliferation or cytotoxic responses. It is concluded that interaction of CTLA-4 with its functional ligands, CD80 or CD86, can down-regulate human T-cell responses, probably by intracellular signalling events and independent of CD28 occupancy.

Published
1999

56. Carnitine biosynthesis. Purification of gamma-butyrobetaine hydroxylase from rat liver

Author

Vaz, F. M., van Gool, S., Ofman, R., IJlst, L., Wanders, R. J., and Other departments

Abstract

gamma-Butyrobetaine hydroxylase catalyse the last step in carnitine biosynthesis, the formation of L-carnitine from gamma-butyrobetaine, a reaction dependent on Fe2+, alpha-ketoglutarate, ascorbate and oxygen. Initial attempts to purify the protein from rat liver showed that gamma-butyrobetaine hydroxylase is unstable. We, therefore, determined the influence of various compounds on the stability of gamma-butyrobetaine hydroxylase at different storage temperatures. The enzyme activity was best conserved by storing the protein at 4 degrees C in the presence of 200 g/l glycerol and 10 mM DTT. We subsequently purified the enzyme from rat liver to apparent homogeneity by liquid chromatography

Published
1999

66. HIGH GRADE GLIOMAS

Author

Leonard, A., primary, Wolff, J., additional, Sengupta, R., additional, Marassa, J., additional, Piwnica-Worms, D., additional, Rubin, J., additional, Pollack, I., additional, Jakacki, R., additional, Butterfield, L., additional, Okada, H., additional, Fangusaro, J., additional, Warren, K. E., additional, Mullins, C., additional, Jurgen, P., additional, Julia, S., additional, Friedrich, C. C., additional, Keir, S., additional, Saling, J., additional, Roskoski, M., additional, Friedman, H., additional, Bigner, D., additional, Moertel, C., additional, Olin, M., additional, Dahlheimer, T., additional, Gustafson, M., additional, Sumstad, D., additional, McKenna, D., additional, Low, W., additional, Nascene, D., additional, Dietz, A., additional, Ohlfest, J., additional, Sturm, D., additional, Witt, H., additional, Hovestadt, V., additional, Quan, D. A. K., additional, Jones, D. T. W., additional, Konermann, C., additional, Pfaff, E., additional, Korshunov, A., additional, Rizhova, M., additional, Milde, T., additional, Witt, O., additional, Zapatka, M., additional, Collins, V. P., additional, Kool, M., additional, Reifenberger, G., additional, Lichter, P., additional, Lindroth, A. M., additional, Plass, C., additional, Jabado, N., additional, Pfister, S. M., additional, Pizer, B., additional, Salehzadeh, A., additional, Brodbelt, A., additional, Mallucci, C., additional, Brassesco, M., additional, Pezuk, J., additional, Morales, A., additional, de Oliveira, J., additional, Roberto, G., additional, Umezawa, K., additional, Valera, E., additional, Rego, E., additional, Scrideli, C., additional, Tone, L., additional, Veringa, S. J. E., additional, Van Vuurden, D. G., additional, Wesseling, P., additional, Vandertop, W. P., additional, Noske, D. P., additional, Wurdinger, T., additional, Kaspers, G. J. L., additional, Hulleman, E., additional, Wright, K., additional, Broniscer, A., additional, Bendel, A., additional, Bowers, D., additional, Crawford, J., additional, Fisher, P., additional, Hassall, T., additional, Armstrong, G., additional, Baker, J., additional, Qaddoumi, I., additional, Robinson, G., additional, Wetmore, C., additional, Klimo, P., additional, Boop, F., additional, Onar-Thomas, A., additional, Ellison, D., additional, Gajjar, A., additional, Cruz, O., additional, de Torres, C., additional, Sunol, M., additional, Rodriguez, E., additional, Alonso, L., additional, Parareda, A., additional, Cardesa, T., additional, Salvador, H., additional, Celis, V., additional, Guillen, A., additional, Garcia, G., additional, Muchart, J., additional, Trampal, C., additional, Martin, M. L., additional, Rebollo, M., additional, Mora, J., additional, Piotrowski, A., additional, Kowalska, A., additional, Coyle, P., additional, Smith, S., additional, Rogers, H., additional, Macarthur, D., additional, Grundy, R., additional, Puccetti, D., additional, Salamat, S., additional, Kennedy, T., additional, Patel, N., additional, Bradley, K., additional, Casey, K., additional, Iskandar, B., additional, Nakano, Y., additional, Okada, K., additional, Osugi, Y., additional, Yamasaki, K., additional, Fujisaki, H., additional, Fukushima, H., additional, Inoue, T., additional, Matsusaka, Y., additional, Sakamoto, H., additional, Hara, J., additional, De Vleeschouwer, S., additional, Ardon, H., additional, Van Calenbergh, F., additional, Sciot, R., additional, Wilms, G., additional, Van Loon, J., additional, Goffin, J., additional, Van Gool, S., additional, Rusinak, D., additional, Knight, P., additional, Onel, K., additional, Wargowski, D., additional, Stettner, A., additional, Al-Ghafari, A., additional, Punjaruk, W., additional, Coyle, B., additional, Kerr, I., additional, Xipell, E., additional, Rodriguez, M., additional, Gonzalez-Huarriz, M., additional, Tunon, M. T., additional, Zazpe, I., additional, Tejada-Solis, S., additional, Diez-Valle, R., additional, Fueyo, J., additional, Gomez-Manzano, C., additional, Alonso, M. M., additional, Pastakia, D., additional, McCully, C., additional, Murphy, R., additional, Bacher, J., additional, Thomas, M., additional, Steffen-Smith, E., additional, Saleem, K., additional, Waldbridge, S., additional, Widemann, B., additional, Warren, K., additional, Miele, E., additional, Buttarelli, F., additional, Arcella, A., additional, Begalli, F., additional, Po, A., additional, Baldi, C., additional, Carissimo, G., additional, Antonelli, M., additional, Donofrio, V., additional, Morra, I., additional, Nozza, P., additional, Gulino, A., additional, Giangaspero, F., additional, Ferretti, E., additional, Elens, I., additional, Pauwels, F., additional, Fritzell, S., additional, Eberstal, S., additional, Sanden, E., additional, Visse, E., additional, Darabi, A., additional, Siesjo, P., additional, McDonald, P., additional, Wrogemann, J., additional, Krawitz, S., additional, Del Bigio, M., additional, Eisenstat, D., additional, Kwiecien, R., additional, Pietsch, T., additional, Faldum, A., additional, Kortmann, R.-D., additional, Warmuth-Metz, M., additional, Rutkowski, S., additional, Slavc, I., additional, Kramm, C. M., additional, Uparkar, U., additional, Geyer, R., additional, Ermoian, R., additional, Ellenbogen, R., additional, Leary, S., additional, Triscott, J., additional, Hu, K., additional, Fotovati, A., additional, Yip, S., additional, Kast, R., additional, Toyota, B., additional, Dunn, S., additional, Hegde, M., additional, Corder, A., additional, Chow, K., additional, Mukherjee, M., additional, Ashoori, A., additional, Brawley, V., additional, Heslop, H., additional, Gottschalk, S., additional, Yvon, E., additional, Ahmed, N., additional, Wong, T.-T., additional, Yang, F.-Y., additional, Lu, M., additional, Liang, H.-F., additional, Wang, H.-E., additional, Liu, R.-S., additional, Teng, M.-C., additional, Yen, C.-C., additional, Agnihotri, S., additional, Ternamian, C., additional, Jones, C., additional, Zadeh, G., additional, Rutka, J., additional, Hawkins, C., additional, Filipek, I., additional, Drogosiewicz, M., additional, Perek-Polnik, M., additional, Swieszkowska, E., additional, Baginska, B. D., additional, Jurkiewicz, E., additional, Perek, D., additional, Kuehn, A., additional, Falkenstein, F., additional, Gnekow, A., additional, Kramm, C., additional, Brooks, M. D., additional, Jackson, E., additional, Mitra, R. D., additional, Rubin, J. B., additional, Liu, X.-Y., additional, Schwartzentruber, J., additional, Fontebasso, A. M., additional, Quang, D.-A. K., additional, Albrecht, S., additional, Dong, Z., additional, Siegel, P., additional, Von Diemling, A., additional, Faury, D., additional, Tabori, U., additional, Majewski, J., additional, Lulla, R., additional, Echevarria, M., additional, Alden, T., additional, DiPatri, A., additional, Tomita, T., additional, Goldman, S., additional, Lin, T., additional, Merchant, T. E., additional, Kocak, M., additional, Panandiker, A. P., additional, Armstrong, G. T., additional, Gielen, G. H., additional, Muehlen, A. z., additional, Hubert, C., additional, Ding, Y., additional, Toledo, C., additional, Paddison, P., additional, Olson, J., additional, Nandhabalan, M., additional, Bjerke, L., additional, Bax, D., additional, Carvalho, D., additional, Bajrami, I., additional, Ashworth, A., additional, Lord, C., additional, Hargrave, D., additional, Reis, R., additional, Workman, P., additional, Little, S., additional, Popov, S., additional, Jury, A., additional, Burford, A., additional, Doey, L., additional, Al-Sarraj, S., additional, Jurgensmeier, J., additional, Chen, L., additional, Kozarewa, I., additional, Baker, S., additional, Perryman, L., additional, Box, G., additional, Raynaud, F., additional, Eccles, S., additional, Viana-Pereira, M., additional, Pereira, M., additional, Forshew, T., additional, Tatevossian, R., additional, Sheer, D., additional, Pimental, J., additional, Pires, M., additional, Sarkar, C., additional, Jha, P., additional, Patrick, I. R. P., additional, Somasundaram, K., additional, Pathak, P., additional, Sharma, M. C., additional, Suri, V., additional, Suri, A., additional, Gerges, N., additional, Haque, T., additional, Nantel, A., additional, Lee, C., additional, Chen, J., additional, Venugopal, C., additional, Singhal, A., additional, Dunham, C., additional, Kerr, J., additional, Verreault, M., additional, Wakimoto, H., additional, Jayanthan, A., additional, Narendran, A., additional, Singh, S., additional, Giraud, G., additional, Holm, S., additional, Gustavsson, B., additional, Kizyma, R., additional, Kizyma, Z., additional, Dvornyak, L., additional, Kotsay, B., additional, Epari, S., additional, Sharma, P., additional, Gurav, M., additional, Gupta, T., additional, Shetty, P., additional, Moiyadi, A., additional, Kane, S., additional, and Jalali, R., additional

Published
2012
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75. Postoperative adjuvant DC vaccination in patients with relapsed high-grade glioma: a prospective, long-term, multivariate analysis in a cohort comparison trial in 66 patients

Author

De Vleeschouwer, S., primary, Fieuws, S., additional, Rutkowski, S., additional, Ardon, H., additional, Van Calenbergh, F., additional, van Loon, J., additional, Goffin, J., additional, Sciot, R., additional, Wilms, G., additional, Demaerel, P., additional, Warmuth-Metz, M., additional, Johannes, E.A.W., additional, Wagner, S., additional, Kaempgen, E., additional, and Van Gool, S., additional

Published
2007
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77. Surgery and adjuvant dendritic cell-based tumour vaccination for patients with relapsed malignant glioma, a feasibility study

Author

Rutkowski, S, primary, De Vleeschouwer, S, additional, Kaempgen, E, additional, Wolff, J E A, additional, Kühl, J, additional, Demaerel, P, additional, Warmuth-Metz, M, additional, Flamen, P, additional, Van Calenbergh, F, additional, Plets, C, additional, Sörensen, N, additional, Opitz, A, additional, and Van Gool, S W, additional

Published
2004
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79. Desmoplastic Infantile Ganglioglioma

Author

De Munnynck, K., primary, Van Gool, S., additional, Van Calenbergh, F., additional, Demaerel, Ph., additional, Uyttebroeck, A., additional, Buyse, G., additional, and Sciot, R., additional

Published
2002
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87. Disease- and treatment-related elevation of the neurodegenerative marker tau in children with hematological malignancies.

Author

Van Gool, S W, Van Kerschaver, E, Brock, P, Pottel, H, Hulstaert, F, Vanmechelen, E, Uyttebroeck, A, Van De Voorde, A, and Vanderstichele, H

Subjects
*LEUKEMIA, *NEUROTOXICOLOGY, *CEREBROSPINAL fluid
Abstract

Children acquire neuropsychologic dysfunctions after chemotherapy for hematologic malignancy. In this study, putative changes in levels of CSF-tau (a marker of neural dysintegrity) in leukemic children prior to and during chemotherapy were studied. Cerebrospinal fluid (CSF) samples were obtained before and during treatment from patients with B cell non-Hodgkin's lymphoma (NHL, n = 10), non-B cell acute lymphoblastic leukemia/NHL (non-B-ALL, n = 48), acute myeloid leukemia (AML, n = 9), other malignant diseases (n = 9), and six control children. A sandwich-type ELISA (INNOTEST hTAU-Ag) was used for measuring CSF-tau. Sixteen out of 50 patients with hematological malignancies, including the patients with proven leukemic CNS invasion, already showed high CSF-tau levels at baseline (>300 pg/ml). The pre-induction treatment for non-B-ALL, consisting of only corticosteroids and methotrexate (MTX), resulted in a significant increase of tau at day 8 (on average to 535 pg/ml). Larger increases as compared to baseline levels of CSF-tau were observed in patients treated for B-NHL with systemic vincristine, corticosteroids and cyclophosphamide, and intrathecal MTX (mean 776 pg/ml at day 8). In two AML patients with CNS invasion, CSF-tau increased during chemotherapy up to 1,500 and 948 pg/ml, respectively. In one non-B-ALL patient with MTX-induced clinical neurotoxicity, CSF-tau was above the detection limit of 2,000 pg/ml. Almost one-third of the patients with hematological malignancies had elevated CSF-tau levels at diagnosis. Transient high levels of CSF-tau, reaching levels observed in other neurodegenerative disorders, were observed during induction chemotherapy for non-B-ALL, B-NHL and CNS+ AML. The clinical implications of both observations will be the subject of further study. [ABSTRACT FROM AUTHOR]

Published
2000
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88. CD57+/CD28- T cells in untreated hemato-oncological patients are expanded and display a Th1-type cytokine secretion profile, ex vivo cytolytic activity and enhanced tendency to apoptosis.

Author

Van den Hove, L E, Van Gool, S W, Vandenberghe, P, Boogaerts, M A, and Ceuppens, J L

Subjects
*CYTOKINES, *T cells, *APOPTOSIS
Abstract

Three-color flow cytometry immunophenotyping revealed significant increases of CD57+ and CD28- cells among both circulating CD4+ and CD8+ T lymphocytes of untreated hemato-oncological patients (n = 54) as compared to healthy donors (n = 55), with CD57 and CD28 expression on the patients' T cells being largely reciprocal. Marked expansion of CD57+ cells among circulating CD4+ T lymphocytes was frequently detected in patients with chronic leukemia of B cell origin (B-CLL, hairy cell leukemia) but not in patients with chronic myeloid leukemia, suggesting a causal relation with the tumor's major histocompatibility complex class II expression. Using immunomagnetic separation techniques, we further demonstrate that the patients' CD57+/CD28- T cells display a typical Th1-type cytokine secretion profile upon anti-CD3 stimulation, with a markedly higher secretion of the Th1-type cytokines IL-2, IFN-gamma, and TNF-alpha than their CD57-/CD28+ counterparts. Cytotoxic activity of circulating CD8+ T lymphocytes, measured ex vivo in an anti-CD3-redirected assay, was almost exclusively exerted by the CD57+/CD28- subset. Moreover, a marked cytotoxic activity was detected within CD4+CD57+ T cells from some B-CLL patients. Finally, the patients' CD57+/CD28- T cells displayed an increased tendency to apoptosis in culture. Collectively, our results indicate that the expanded CD57+/CD28- T cells in hemato-oncological patients represent differentiated effector cells, similar to their (quantitatively minor) counterpart in healthy donors. The reason for their expansion and their pathophysiologic significance, however, remains unclear. [ABSTRACT FROM AUTHOR]

Published
1998
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89. Expression of B7-2 (CD86) molecules by Reed-Sternberg cells of Hodgkin's disease.

Author

Van Gool, S W, Delabie, J, Vandenberghe, P, Coorevits, L, De Wolf-Peeters, C, and Ceuppens, J L

Subjects
*HODGKIN'S disease, *TUMOR immunology, *T cells
Abstract

Ligation of CD28 on T cells with its natural ligands B7-1 (CD80) or B7-2 (CD86) provides a major costimulatory signal for T cells and is of potential importance for tumor rejection. We previously reported a strong expression of B7-1 on Reed-Sternberg cells and anaplastic large cell lymphoma cells. We report here our findings on B7-2 expression by malignant lymphomas (n = 70). B7-2 was present on the neoplastic cells of anaplastic large cell lymphoma in two of three cases studied, and on a subpopulation of the malignant cells in one out of four cases of follicular lymphoma. B7-2 was not expressed by the neoplastic cells of the other non-Hodgkin's lymphomas (n = 32), including T cell-rich B cell lymphoma. In contrast, Reed-Sternberg cells in lymph nodes affected by Hodgkin's disease are strongly positive for B7-2 (n = 31). Evidence for a functional correlate of this expression was obtained by our findings that the combination of anti-B7-1 and anti-B7-2 monoclonal antibodies was more effective than each separately in blocking allogeneic T cell activation (proliferation and cytokine secretion) by Hodgkin's disease-derived cell lines as stimulators. The possible role of B7-1 and B7-2 expression for the course and symptomatology of Hodgkin's disease is discussed. [ABSTRACT FROM AUTHOR]

Published
1997
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90. CD40 triggering of chronic lymphocytic leukemia B cells results in efficient alloantigen presentation and cytotoxic T lymphocyte induction by up-regulation of CD80 and CD86 costimulatory molecules.

Author

Van den Hove, L E, Van Gool, S W, Vandenberghe, P, Bakkus, M, Thielemans, K, Boogaerts, M A, and Ceuppens, J L

Subjects
*LYMPHOCYTIC leukemia, *B cells
Abstract

Freshly collected chronic lymphocytic leukemia B cells (B-CLL cells) are known to be inefficient at stimulating allogeneic T cells, and to lack significant expression of B7 (CD80 and CD86) costimulatory molecules. We investigated the potential of CD40 triggering to up-regulate the expression of adhesion and costimulatory molecules on B-CLL cells, and to enhance their immunogenicity towards allogeneic T cells. B-CLL cells cocultured with human CD40 ligand-expressing mouse fibroblasts rapidly up-regulated CD54 and CD58 adhesion molecules and B7-1 (CD80) and B7-2 (CD86) costimulatory molecules, and acquired a strong stimulatory capacity towards CD4+ as well as isolated CD8+ allogeneic T cells. Costimulation by both CD80 and CD86 proved critical for allogeneic T cell proliferation and CD25 and HLA-DR expression, since these were strongly inhibited by anti-CD80 or anti-CD86 monoclonal antibodies, and completely abrogated by CTLA4-Ig fusion protein, which blocks both CD80 and CD86. B7 costimulation also proved critical for restimulation of primed B-CLL-reactive T cells. Most importantly, priming of purified CD8+ T cells with CD40-triggered allogeneic B-CLL cells resulted in cytotoxic activity against the unstimulated B-CLL cells. These findings raise the possibility that CD40 triggering of B-CLL cells might be exploited in immunotherapeutic protocols. [ABSTRACT FROM AUTHOR]

Published
1997
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91. Accessory Signalling by B7-1 for T Cell Activation Induced by Anti-CD2: Evidence for IL-2-Independent CTL Generation and CsA-Resistant Cytokine Production.

Author

Van Gool, S. W., Kasran, A., Wallays, G., De Boer, M., and Ceuppens, J. L.

Subjects
T cells, ANTIGEN presenting cells, FIBROBLASTS, CELL proliferation, CYTOKINES, LYMPHOCYTES
Abstract

Resting T cells can be activated by selected pairs of anti-CD2 MoAb. Activation is dependent on the presence of accessory cells, which can be replaced by either anti-CD28, or by the combination of IL-1β and IL-6. The present study was undertaken to investigate accessory signalling by B7-1, the natural ligand of CD28, in this pathway of T cell activation. 3T6 mouse fibroblasts were transfected with human B7-1 and used as accessory cells in cultures of purified resting human T cells. In the presence of a stimulating pair of anti-CD2 MoAb, T cell proliferation, production of cytokines (IL-2, IL-4, IL-10, GM-CSF, IFN-γ and TNF-α), and generation of cytotoxic T lymphocytes were all supported by B7-1(+) 3T6 cells but not by control 3T6 cells. Blocking studies with anti-IL-2 + anti-IL-2R MoAb revealed both IL-2-dependent and IL-2-independent CTL generation after B7-1-mediated costimulation. Moreover, a partial or complete resistance to inhibition with CsA was observed for IL-2 production and CTL generation respectively in the presence of the costimulatory signal derived from B7-1 - CD28 interaction. Anti-CD2 MoAb with B7-1 costimulation could directly induce proliferation, IL-2 production and generation of CTL activity in highly purified CD8+ T cells without the help of CD4+ T cells. We conclude that CD28 ligation with the natural ligand B7-1 provides a strong accessory signal for CD4 and CD8 cell activation through CD2. [ABSTRACT FROM AUTHOR]

Published
1995
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92. T Helper-Independent Activation of Human CD8+ Cells: the Role of CD28 Costimulation.

Author

Van Gool, S. W., Yiqun Zhang, Kasran, A., De Boer, M., and Ceuppens, J. L.

Subjects
MHC antibodies, CELLS, T cells, ANTIGEN presenting cells, MICE
Abstract

The concept that activation of MHC class I-restricted CD8+ cells entirely depends on help from MHC class II-restricted CD4+ T cells has recently been supplemented with an alternative model in which CD8+ cells can directly be activated by MHC class I-expressing professional antigen-presenting cells (APC), which are able to deliver an accessory signal. The authors analysed the role of CD28-mediated costimulation for T helper cell-independent activation of purified human CD8+ T cells in two different in vitro models. Freshly isolated CD8+ cells could be activated (proliferation, IL-2 production and cytotoxic activity) by anti-CD3-presenting FcγR+ mouse cells transfected with the human CD28 ligand, CD80, as the only accessory signal. On the other hand, activation of CD8+ cells by allogeneic MHC class I on EBV-transformed B cells, which express two different CD28 ligands, CD80 and CD86, also proceeded very efficiently (proliferation, cytotoxic activity and CD25 expression), but was either not, or only partially, blocked by anti-CD80 and anti-CD86 MoAb or CTLA-4Ig. This indicates that other costimulatory signals are also effective, and that CD28 triggering is not absolutely required for initial T-cell activation. CsA and CD80/CD86-blocking agents were synergistic in completely inhibiting activation of CD8+ cells in the MLR with allogeneic B-cell lines. This combination also induced non-responsiveness of CD8+ cells upon restimulation in the absence of blocking agents. Therefore, although professional APC can apparently provide multiple costimulatory signals for direct activation of CD8+ T cells, the signal derived from CD80/CD86 is unique in providing CsA-resistance. [ABSTRACT FROM AUTHOR]

Published
1996
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94. Effects of co-stimulation by CD58 on human T cell cytokine production: a selective cytokine pattern with induction of high IL-10 production.

Author

Bullens, D M, Rafiq, K, Charitidou, L, Peng, X, Kasran, A, Warmerdam, P A, Van Gool, S W, and Ceuppens, J L

Abstract

CD58 is the ligand for the CD2 molecule on human T cells and has been shown to provide a co-stimulatory signal for T cell activation. However, its physiological role is still unclear. We studied the effects of co-stimulation by CD58 on the production of T(h)1-type (IL-2- and IFN-gamma) or T(h)2 type (IL-4, IL-5 and IL-10) cytokines in an in vitro culture system of purified human T cells with CD58-transfected P815 cells and with anti-CD3 as the primary stimulus. Co-stimulation of T cells by CD58 potently induced IL-10 and IFN-gamma production (at the protein and at the mRNA level), and transforming growth factor-ss production (at the mRNA level), comparable to what can be found in CD80 co-stimulated T cell cultures. In contrast, we found low to absent IL-2, IL-4, IL-5, IL-13 and tumor necrosis factor-alpha production after CD58 co-stimulation, and this was not due to suppressive effects of endogenously produced IL-10. CD80 co-stimulation strongly induced all these cytokines. Intracellular staining for cytokine expression revealed the existence of a T cell subpopulation induced by CD58 co-stimulation to produce both IFN-gamma and IL-10. We furthermore found that the selective cytokine profile induced by CD58 co-stimulation is further accentuated by rIL-12 and by rIFN-alpha. Using cyclosporin A as an inhibitor of the calcineurin enzyme, we could show that production of all cytokines in this system is calcium dependent. CD58 co-stimulation thus induces a cytokine pattern corresponding to that described for T regulatory (T(r)) 1 cells and to the pattern reported to be induced by the newly identified B7 family member, B7-H1.

Published
2001
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95. B7-CD28 interaction is a late acting co-stimulatory signal for human T cell responses.

Author

Zhang, Y Q, Joost van Neerven, R J, Van Gool, S W, Coorevits, L, de Boer, M, and Ceuppens, J L

Abstract

The interaction of CD28 with one of the B7 molecules (CD80 and CD86) on professional antigen-presenting cells (APC) is generally considered as the most important co-stimulatory signal for T cell activation. APC in a resting condition express either no or only low levels of B7 molecules. These are up-regulated as a result of interactions with activated T cells, thus suggesting that B7-CD28 interaction is not required at initiation of T cell activation. To study this issue, we blocked B7-CD28 interaction at various time points after in vitro stimulation of peripheral blood T cells with allogeneic monocytes. Epstein-Barr virus-transformed B cells or soluble antigens. We observed that T cell proliferation and IL-2 production were inhibited by B7-blocking agents (CTLA-4-Ig or anti-B7 mAb) almost to the same degree when added either at initiation of culture or 24 h later. B7-blocking agents still resulted in significant inhibition of allogeneic T cell activation when added after 48 h. Furthermore, when CTLA-4-Ig was added at the start of an allogeneic T cell stimulation, addition of anti-CD28 mAb after 24 h of culture nearly fully restored T cell proliferation to control levels. Finally, we demonstrate that delayed addition of B7-blocking agents together with cyclosporin A 1 day after the onset of culture of T cells with allogeneic B cells is highly efficient to induce energy as evaluated by lack of proliferation, cytotoxic T lymphocyte reactivity and IFN-gamma or IL-5 production upon alloantigen rechallenge. Taken together, our data can explain why B7 expression on APC is not required at the time of initial APC-T cell contact, and suggest that the effect of the CD28 signal indeed consists in prolonging IL-2 production and amplifying T cell responses, rather than in providing a critical co-stimulatory signal at the time of initial TCR triggering.

Published
1997
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96. HIGH GRADE GLIOMAS AND DIPG

Author

Classen C, William D, Linnebacher M, Farhod A, Kedr W, Elsabe B, Fadel S, Van Gool S, De Vleeschouwer S, Koks C, Garg A, Ehrhardt M, Riva M, and Judkins A

97. Compendium Echtscheiding

Author

Coenraad, L. M., Gerard Staats, Stollenwerck, A. H. N., Bie, A. V. T., Boshouwers, K. A., Breederveld, B., Ebben, E., Gompel, P. J. T., Hulten, L. C., Jongekrijg, J. C., Knot, J. G., Kraan, E. E., Leonhard-Strien, W. H. A., Mos-Van Gool, S., Smits, V. M., Vries, B. A., Department of Tax Economics, and Fiscal Institute Tilburg (FIT)

Subjects
levensverzekeringen, Lijfrente, echscheiding, kapitaalverzekering, huwelijksvermogensrecht, scheiding
Abstract

Diverse auteurs gaan in op aspecten rondom scheiding

98. Immunotherapy with subcutaneous immunogenic autologous lysate against glioblastoma : Immunotherapie met subcutaan immunogeen autoloog tumor lysaat tegen glioblastomen

Author

Belmans, J, Locquet, J-P, Van Gool, S, and Bullens, D

Abstract

Being diagnosed with glioblastoma (GBM) is related to a grim future, with patients showing a median overall survival of less than 15 months despite intensive radio- and chemotherapy. As a consequence, the scientific community is searching for adjuvant treatment modalities that might improve the outcome of this devastating disease. In this regard, immunotherapy has gained great interest. One immunotherapeutic strategy uses dendritic cells (DCs) to generate an anti-tumor response induced by the patient's own immune system. This DC-based active immunotherapy consists of two groups using either ex vivo grown DCs or in vivo targeting of these cells. The latter condition might be preferred because of efficiency, variable response rates of ex vivo grown DCs plus limited migration to lymphoid tissue, as well as practical and economic reasons (time-consuming, labour-intensive process requiring sterile handling leading to an expensive vaccine). In order to induce a broader immune response against the cancer cells and because of the strong heterogeneity of these tumors, whole tumor cell lysate is being preferred as an antigenic source in glioma. Moreover, we were wondering if the tumor lysate vaccination could benefit from the implementation of nanoparticles (NPs) in this treatment. These small particles are able to improve DC immunotherapy for example by their variable physicochemical properties, by combining antigen and adjuvant internalisation and by rendering the opportunity to target DCs in vivo. To achieve this goal, a nanovaccine was generated by surface loading polystyrene NPs with whole tumor lysate and this way aiming for a passive targeting of DCs following subcutaneous injection. Based on the knowledge our research group obtained concerning the strength of the immunogenic signature of our lysate product, we investigated the potential effect and immune mechanisms of naked autologous immunogenic tumor lysate and lysate-NP conjugates, without the addition of DCs or adjuvants, to treat GBM in a preclinical mouse model. Following proof of antigen internalisation by DCs in vitro and subsequent antigen processing and presentation, a positive survival effect in preclinical murine glioma models was observed by subcutaneous lysate injections. Next, the process of nanovaccine generation was started by stably conjugating lysate to the surface of NPs. Following an optimisation process which judged size, antigen conjugation, in vitro DC internalisation and, in a limited manner, toxicity, the most ideal nanovaccine composition was tested in the glioma mouse models. Comparable results as for autologous lysate treatment were observed, showing survival benefit of subcutaneous nanovaccine administrations. In both treatment modalities, the immune response was characterized by an increase of T cells and a diminished immune suppression in the brain, with the induction of a tumor-specific immunological memory. Finally, combinatorial treatment strategies of autologous lysate vaccination or nanovaccine with TMZ chemotherapy lead to ameliorated survival outcome in glioma-bearing mice. The presented work demonstrated that subcutaneous injection of autologous whole tumor lysate can dose-dependently initiate an immune response that suppresses tumor growth of gliomas. The effectiveness of lysate treatment for gliomas offers a time and cost-effective approach in comparison to DC therapy, and thus it should be considered as a potential adjuvant treatment for glioma. With the nanovaccine research we aimed for a feasibility proof-of-concept study for using lysate-loaded NPs in the treatment of GBM that can be expanded in future. Further optimisation of a nanovaccine e.g. by co-delivery of antigens and immune adjuvants or active targeting of DCs, might be the future for autologous lysate vaccination. status: published

Published
2019

100. Molecular and Translational Classifications of DAMPs in Immunogenic Cell Death

Author

Abhishek D Garg, Lorenzo eGalluzzi, Lionel eApetoh, Thais eBaert, Raymond B Birge, Jose Manuel Bravo-San Pedro, Karine eBreckpot, David eBrough, Ricardo eChaurio, Mara eCirone, An eCoosemans, Pierre G Coulie, Dirk eDe Ruysscher, Luciana eDini, Peter ede Witte, Aleksandra M Dudek-Peric, Alberto eFaggioni, Jitka eFucikova, Udo S Gaipl, Jakub eGolab, Marie-Lise eGougeon, Michael R Hamblin, Akseli eHemminki, Martin eHerrmann, James W. Hodge, Oliver eKepp, Guido eKroemer, Dmitri V Krysko, Walter G Land, Frank eMadeo, Angelo A. Manfredi, Stephen R. Mattarollo, Christian eMaueroder, Nicolò eMerendino, Gabriele eMulthoff, Thomas ePabst, Jean-Ehrland eRicci, Chiara eRiganti, Erminia eRomano, Nicole eRufo, Mark J. Smyth, Jürgen eSonnemann, Radek eSpisek, John eStagg, Erika eVacchelli, Peter eVandenabeele, Lien eVandenberk, Benoit J Van Den Eynde, Stefaan Willy Van Gool, Francesca eVelotti, Laurence eZitvogel, Patrizia eAgostinis, Research Programs Unit, Translational Cancer Biology (TCB) Research Programme, Medicum, Transplantation Laboratory, Garg, Ad, Galluzzi, L, Apetoh, L, Baert, T, Birge, Rb, Bravo San Pedro, Jm, Breckpot, K, Brough, D, Chaurio, R, Cirone, M, Coosemans, A, Coulie, Pg, De Ruysscher, D, Dini, L, de Witte, P, Dudek Peric, Am, Faggioni, A, Fucikova, J, Gaipl, U, Golab, J, Gougeon, Ml, Hamblin, Mr, Hemminki, A, Herrmann, M, Hodge, Jw, Kepp, O, Kroemer, G, Krysko, Dv, Land, Wg, Madeo, F, Manfredi, ANGELO ANDREA M. A., Mattarollo, Sr, Maueroder, C, Merendino, N, Multhoff, G, Pabst, T, Ricci, Je, Riganti, C, Romano, E, Rufo, N, Smyth, Mj, Sonnemann, J, Spisek, R, Stagg, J, Vacchelli, E, Vandenabeele, P, Vandenberk, L, Van den Eynde, Bj, Van Gool, S, Velotti, F, Zitvogel, L, Agostinis, P., Dini, Luciana, Manfredi, Aa, Medicine and Pharmacy academic/administration, Laboratory of Molecullar and Cellular Therapy, Basic (bio-) Medical Sciences, Chemistry, and UCL - SSS/DDUV - Institut de Duve

Subjects
medicine.medical_treatment, APOPTOTIC CALRETICULIN EXPOSURE, anti-tumor immunity, immunogenicity, PHOTODYNAMIC THERAPY, 0302 clinical medicine, translational medicine, oncoimmunology, Immunology and Allergy, Cytotoxic T cell, Medicine, Anti-tumor immunity, Immunogenicity, Immunotherapy, Molecular medicine, Oncoimmunology, Patient prognosis, Translational medicine, Immunology, 0303 health sciences, immunotherapy, molecular medicine, patient prognosis, RIBOSOMAL-PROTEIN DIMER, Classification, ddc, 3. Good health, 030220 oncology & carcinogenesis, Immunogenic cell death, Molecular Medicine, ACTIVATING POLYPEPTIDE-II, HIGH HYDROSTATIC-PRESSURE, lcsh:Immunologic diseases. Allergy, ANTICANCER IMMUNE-RESPONSES, 3122 Cancers, 610 Medicine & health, 03 medical and health sciences, Immune system, HUMAN TUMOR-CELLS, FORMYL PEPTIDE RECEPTORS, 030304 developmental biology, business.industry, Biology and Life Sciences, CYTOTOXIC T-LYMPHOCYTES, Dendritic cell, NEGATIVE BREAST-CANCER, Cancer cell, molecular dicine, 3111 Biomedicine, business, lcsh:RC581-607
Abstract

The immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology of neoplastic cells. It is now clear that cancer cells can succumb to some anticancer therapies by undergoing a peculiar form of cell death that is characterized by an increased immunogenic potential, owing to the emission of the so-called "damage-associated molecular patterns" (DAMPs). The emission of DAMPs and other immunostimulatory factors by cells succumbing to immunogenic cell death (ICD) favors the establishment of a productive interface with the immune system. This results in the elicitation of tumor-targeting immune responses associated with the elimination of residual, treatment-resistant cancer cells, as well as with the establishment of immunological memory. Although ICD has been characterized with increased precision since its discovery, several questions remain to be addressed. Here, we summarize and tabulate the main molecular, immunological, preclinical, and clinical aspects of ICD, in an attempt to capture the essence of this phenomenon, and identify future challenges for this rapidly expanding field of investigation. ispartof: Frontiers in Immunology vol:6 issue:NOV ispartof: location:Switzerland status: published

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