. . "0"^^ . "Mechanismus \u00FA\u010Dinku polymern\u00EDch l\u00E9\u010Div a jejich intracelul\u00E1rn\u00ED distribuce" . . "http://www.isvav.cz/projectDetail.do?rowId=GP305/04/P004"^^ . "0"^^ . "2"^^ . "2"^^ . "Mechanism of action of polymeric drugs and their intracellular distribution"@en . "1"^^ . "At present, the polymeric conjugates based on poly N-(2-hydroxypropyl)-methacrylamide (HPMA) [1-7] are used as a carriers for anticancer drug - doxorubicin. Conjugation of doxorubicin with a polymeric carrier and optionally targeted with targeting structure, strongly influences its physico-chemical character. This is the reason why different forms of polymeric conjugates enter the cells via different pathways [9]. To improve the properties of currently used anticancer polymeric conjugates the detailed characterization of pharmacokinetics, drug action, internalization, anticancer effect and unwanted side-effects is necessary. The techniques of fluorescence microscopy and confocal microscopy will be used to follow the subcellular localization and intracellular trafficking of free doxorubicin as well as new polymeric conjugates, to visualize drug dependent changes in the organization of organelles (mitochondria, Golgi apparatus, lysozomes, ER) and to distinguish between the apoptotic and"@en . . "The key factor determining the efficacy of polymer conjugates based on N-(2-hydroxypropyl)methacrylamide (HPMA) coupled to doxorubicin (Dox) via a proteolytically cleavable spacer is not the release of doxorubicin from its peptidic spacer, but the rate a"@en . . . "Rozhoduj\u00EDc\u00EDm parametrem ovliv\u0148uj\u00EDc\u00EDm \u00FA\u010Dinnost polymern\u00EDch konjug\u00E1t\u016F na b\u00E1zi N-(2-hydroxypropyl)methacrylamidu (HPMA) nesouc\u00EDch doxorubicin nav\u00E1zan\u00FD na polymern\u00ED nosi\u010D pomoc\u00ED proteolyticky \u0161t\u011Bpiteln\u00E9 vazby nen\u00ED \u0161t\u011Bpitelnost peptidov\u00E9 spojky, ale rychlost"@cs . . "GP305/04/P004" . . . . "Neuvedeno."@en . . . . . . . . "Jako polymern\u00ED nosi\u010De cytostatika doxorubicinu jsou v sou\u010Dasnosti vyu\u017E\u00EDv\u00E1ny kopolymery na b\u00E1zi N-(2-hydroxypropyl)-methakrylamidu (HPMA ) [1-7]. Po nav\u00E1z\u00E1n\u00ED cytostatika -doxorubicinu na polymern\u00ED nosi\u010D, kter\u00FD m\u016F\u017Ee n\u00E9st i sm\u011Brovac\u00ED strukturu, je podstatn\u011Bovlivn\u011Bn fyzik\u00E1ln\u011B-chemick\u00FD charakter tohoto l\u00E9\u010Diva. To je d\u016Fvod pro\u010D r\u016Fzn\u00E9 formy polymern\u00EDch konjug\u00E1t\u016F vstupuj\u00ED do n\u00E1dorov\u00FDch bun\u011Bk odli\u0161n\u00FDmi mechanismy [9]. V\u00FDvoj nov\u00FDch generac\u00ED protin\u00E1dorov\u00FDch l\u00E9\u010Div s vy\u0161\u0161\u00EDm terapeutick\u00FDm potenci\u00E1lem je podm\u00EDn\u011Bn dokonalou anal\u00FDzou farmakokinetiky, mechanismu protin\u00E1dorov\u00E9ho \u00FA\u010Dinku, zp\u016Fsobu internalizace a ne\u017E\u00E1douc\u00EDch vedlej\u0161\u00EDch \u00FA\u010Dink\u016F pou\u017E\u00EDvan\u00FDch struktur. Pro sledov\u00E1n\u00ED intracelul\u00E1rn\u00ED distribuce a voln\u00E9ho doxorubicinu a modifikovan\u00FDch forem polymern\u00EDch konjug\u00E1t\u016Fa pro stanoven\u00ED jejich vlivu na organely (mitochondrie, Golgiho apar\u00E1t, lysoz\u00F3my, endocytick\u00FD kompartment, ER) a anal\u00FDzu odli\u0161en\u00ED apoptotick\u00E9 a/nebo nekrotick\u00E9 smrti, pou\u017Eijeme fluorescen\u010Dn\u00ED a konfok\u00E1ln\u00ED mikroskop. Z\u00EDskan\u00E9 \u00FAdaje pak v kombinaci s" . . "2007-10-16+02:00"^^ . . . .