"0"^^ . "Nejv\u00FDznamn\u011Bj\u0161\u00ED v\u00FDsledky: 1)protin\u00E1dorov\u00E1 \u00FA\u010Dinnost v\u00EDcejadern\u00E9ho komplexu platiny BBR3464 je ur\u010Dena tvorbou m\u016Fstk\u016F del\u0161\u00EDho dosahu, kter\u00E9 vytvo\u0159\u00ED toto cytostatikum v DNA, co\u017E br\u00E1n\u00ED opraven\u00ED t\u011Bchto po\u0161kozen\u00ED NER; 2) pochopen\u00ED \u00FAlohy protein\u016F XPA a RPA a"@cs . "Rozli\u0161en\u00ED a oprava po\u0161kozen\u00ED DNA platinov\u00FDmi cytostatiky.Vztah k v\u00FDvoji nov\u00FDch l\u00E9\u010Div proti rakovin\u011B." . "2003-07-31+02:00"^^ . . "cancer" . "platinum" . . "14"^^ . . "Recognition and repair of DNA damage by antitumor platinum drugs.Relations to the development of new anticancer drugs."@en . "14"^^ . . . . . "DNA" . . . "NL6058" . . . "http://www.isvav.cz/projectDetail.do?rowId=NL6058"^^ . "0"^^ . . . "1"^^ . "Cytotoxicita platinov\u00FDch komplex\u016F z\u00E1vis\u00ED v n\u00E1dorov\u00FDch bu\u0148k\u00E1ch na typu,po\u010Dtu a distribuci neopraviteln\u00FDch po\u0161kozen\u00ED DNA.Oprava po\u0161kozen\u00E9 DNA je tedy d\u016Fle\u017Eit\u00FDm faktorem,kter\u00FD ur\u010Duje klinickou \u00FA\u010Dinnost.Testov\u00E1ny budou n\u00E1sleduj\u00EDc\u00ED pracovn\u00ED hypot\u00E9zy. Rozpozn\u00E1n\u00ED adukt\u016F vytvo\u0159en\u00FDch na DNA komplexy platiny slo\u017Ekami nukleotidov\u00E9 excizn\u00ED opravy(NER),vyskytuj\u00EDc\u00EDmi se v lidsk\u00FDch bu\u0148k\u00E1ch,z\u00E1vis\u00ED na schopnosti t\u011Bchto adukt\u016F destabilizovat dvou\u0161roubovici DNA. Aby bylo dosa\u017Eeno klinicky vyu\u017Eiteln\u00E9 protin\u00E1dorov\u00E9 \u00FA\u010Dinnosti,je nezbytn\u00FD vznik takov\u00E9ho aduktu,kter\u00FD naru\u0161uje pravideln\u00E9 uspo\u0159\u00E1d\u00E1n\u00ED dvojit\u00E9 \u0161roubovice DNA,ani\u017E by do\u0161lo ve v\u00FDrazn\u00E9 m\u00ED\u0159e k vyvol\u00E1n\u00ED d\u011Bj\u016F vedouc\u00EDch k NER. S c\u00EDlem prov\u011B\u0159it tyto hypot\u00E9zy experiment\u00E1ln\u011B,budou p\u0159ipraveny pr\u00F3by DNA obsahuj\u00EDc\u00ED jedin\u00FD adukt komplexu platiny v p\u0159edem zvolen\u00FDch sekvenc\u00EDch nukleotid\u016F.Testov\u00E1na bude \u00FA\u010Dinnost slo\u017Eek lidsk\u00E9ho NER tyto adukty opravovat." . . "Repair" . "antitumor drugs" . "Cytotoxicity of platinum antitumor drugs depends on the type, number and distribution of unrepaired DNA lesions in cancer cells.Dna repair is likely to be an important determinant of clinical efficacy.The following hypothesis will be tested: Recognition of platinum-DNA adducts by human nucleotide excision repair (NER) depends on their ability to destabilize DNA double-helix. To achieve biological and clinical efficacy,it is necessary to obtain platinum-DNA adducts that distort the double helix without eliciting substantial exision repair responses. To test these hypotheses experimentally,a series of DNA substrates containing a single site-specific platinum adduct at a specific position will be designed and purified.The capacity of human NER to process these site-directed adducts will be tested."@en . "conformation" . . . . "Repair;DNA;platinum;cancer;antitumor drugs;conformation;recognition"@en .