. "3196"^^ . . "Management of neoplastic diseases is one of the greatest challenges of medicine. Amongst the most difficult cancers are malignant mesotheliomas (MM) with no current treatment. Vitamin E analogues, epitomised by alpha-tocopheryl succinate (a-TOS), present a promise as potential anti-mesothelioma agents. We showed that a-TOS induced selective apoptosis in MM cells, sensitises them to TRAIL, and suppresses MM in mouse models. The precise mechanisms, by which a-TOS induces apoptotic signaling, sensitises cells to TRAIL, and by which it shows selectivity to MM cells, are not known. This project will delineate these pathways using a novel approach, in which cells will be treated and probed for activation of signalling pathways using genomic and proteomic approaches. We will use l;atest techniques to study expression on the level of mRNA and protein and on the level of post-translational modifications. These results will help transfer of vitamin E analogues into clinical practice."@en . "1"^^ . . "Cell death pathways in mesothelioma cells exposed to pharmacological and immunological inducers of apoptosis: genomic and proteomic approach"@en . . . . . . "3196"^^ . . "L\u00E9\u010Dba neoplastick\u00FDch chorob pat\u0159\u00ED k nejv\u011Bt\u0161\u00EDm v\u00FDzv\u00E1m sou\u010Dasn\u00E9 medic\u00EDny. Mezi nejobt\u00ED\u017En\u011Bj\u0161\u00ED typy rakoviny pat\u0159\u00ED malign\u00ED mesotheliomy (MM), pro n\u011B\u017E v sou\u010Dasnosti neexistuje l\u00E9\u010Dba. Analogy vitaminu E, representovan\u00E9 alfa-tokoferyl sukcin\u00E1tem (a-TOS) p\u0159edstavuj\u00ED velmi nad\u011Bjn\u00E9 l\u00E1tky s protimesothelion\u00E1ln\u00EDm \u00FA\u010Dinkem. Prok\u00E1zali jsme, \u017Ee a-TOS vyvol\u00E1v\u00E1 v MM bun\u011B\u010Dn\u00FDch lini\u00EDch, kter\u00E9 jsou relativn\u011B resistentn\u00ED v\u016F\u010Di jin\u00FDm induktor\u016Fm, selektivn\u00ED apoptosu, \u017Ee je zcitlivuje v\u016F\u010Di imunologick\u00E9mu induktoru TRAILu, a \u017Ee potla\u010Duje MM v my\u0161\u00EDch modelech. P\u0159esn\u00E9 mechanismy, jimi\u017E a-TOS vyvol\u00E1v\u00E1 apoptosu, nejsou zn\u00E1my. Tento projekt se soust\u0159ed\u00ED na nalezen\u00ED takov\u00FDchto sign\u00E1ln\u00EDch drah a jejich anal\u00FDzu pomoc\u00ED genomick\u00FDch a proteomick\u00FDch technik. V t\u00E9to pr\u00E1ci budou pou\u017Eity nejnov\u011Bj\u0161\u00ED technologie, kter\u00E9 umo\u017En\u00ED studium pr\u00EDslu\u0161n\u00FDch drah na z\u00E1klad\u011B exprese gen\u016F na \u00FArovni mRNA a proteinu, ale tak\u00E9 na \u00FArovni post-transla\u010Dn\u00EDch modifikac\u00ED. Tyto poznatky umo\u017En\u00ED budouc\u00ED p\u0159enesen\u00ED analog\u016F vitaminu E do klinick\u00E9 praxe."@cs . "Sign\u00E1ln\u00ED dr\u00E1hy bun\u011B\u010Dn\u00E9 smrti v mesotheliom\u00E1ln\u00EDch bu\u0148k\u00E1ch d\u00EDky \u00FA\u010Dinku farmakologick\u00FDch a imunologick\u00FDch induktor\u016F apoptosy: genomick\u00FD a proteomick\u00FD p\u0159\u00EDstup"@cs . . . "3"^^ . "0"^^ . "5"^^ . "2006-01-01+01:00"^^ . "Proteomics; genomics; mesotheliomas; vitamin E analogues; immunological inducers"@en . "2008-12-31+01:00"^^ . . "5"^^ .