"1"^^ . "fluoropyrimidines; toxicity; DPD; mutation; sequencing; qRT-PCR; dihydropyrimidinase; hypermethylation"@en . . "1"^^ . "1A8708" . "fluoropyrimidines" . . "The aim of the project is pharmacogenomic analysis of the severe toxicity development following fluoropyrimidines treatment, focused on catabolic enzymes of their metabolism DPD and DPYS. A clinical utilization of the analysis will be evaluated. Using molecular biology approaches we will perform analysis of a) mutation in DPYD/DPYS b) their expression c) DPYD promoter in population of patients treated by fluoropyrimidines w/wo toxicity. Population frequency of mutations will be performed. Mutations will be studied by DHPLC/sequencing. Novel mutations will be characterized by computer modeling of protein structure. Expression will be quantified by real-time PCR. Promoter sequences will be studied by methylation-specific PCR/sequencing. Statistical analysis of results and their correlation with clinical data allows assessment of: reduction of morbidity and mortality, treatment efficacy in patients w/wo pharmacogenomic analysis and evaluation of inpatient and treatment costs."@en . . " qRT-PCR" . . . "0"^^ . . "http://www.isvav.cz/projectDetail.do?rowId=1A8708"^^ . "The result of the project are new biological and clinical information that solves issues related toxicity of cancer treatment and specification of genetic and epigenetic factors of the patient"@en . "Anal\u00FDza genetick\u00FDch a epigenetick\u00FDch faktor\u016F vedouc\u00EDch k rozvoji projev\u016F z\u00E1va\u017En\u00E9 a\u017E let\u00E1ln\u00ED toxicity l\u00E9\u010Dby fluoropyrimidiny u onkologick\u00FDch pacient\u016F" . " mutation" . "2005-08-01+02:00"^^ . " sequencing" . " DPD" . . "C\u00EDlem projektu je farmakogenomick\u00E1 anal\u00FDza vzniku z\u00E1va\u017En\u00E9 toxicity po aplikaci fluoropyrimidin\u016F, zam\u011B\u0159en\u00E1 na katabolick\u00E9 enzymy jejich metabolismu - dihydropyrimidindehydrogen\u00E1zu (DPD) a dihydropyrimidin\u00E1zu (DPYS), a mo\u017Enosti jej\u00ED klinick\u00E9 aplikace. Pomoc\u00ED metod molekul\u00E1rn\u00ED biologie provedeme u pacient\u016F s/bez v\u00FDskytu z\u00E1va\u017En\u00E9 toxicity a) muta\u010Dn\u00ED anal\u00FDzy DPYD/DPYS b) anal\u00FDzu jejich exprese, c) anal\u00FDzu promotoru DPYD. Ur\u010Den\u00ED frekvence mutac\u00ED bude provedeno na vzorc\u00EDch neselektovan\u00E9 populace Muta\u010Dn\u00ED anal\u00FDza bude provedena kombinac\u00ED DHPLC/sekvenov\u00E1n\u00ED. Nov\u00E9 mutace budou studov\u00E1ny pomoc\u00ED molekul\u00E1rn\u00EDho modelov\u00E1n\u00ED. Exprese bude kvantifikov\u00E1na real-time RT-PCR. Promotorov\u00E9 sekvence budou studov\u00E1ny pomoc\u00ED metyl specifick\u00E9ho PCR/sekvenov\u00E1n\u00ED. Po statistick\u00E9 anal\u00FDze v\u00FDsledk\u016F bude vyhodnoceno: zkr\u00E1cen\u00ED doby hospitalizace, morbidity a mortality, \u00FA\u010Dinnosti terapie u pacient\u016F l\u00E9\u010Den\u00FDch fluoropyrimidiny s/bez farmakogenomick\u00E9 anal\u00FDzy p\u0159edch\u00E1zej\u00EDc\u00ED l\u00E9\u010Dbu." . "5"^^ . " toxicity" . "5"^^ . . . . . . "2008-03-05+01:00"^^ . . . "ANALYSIS OF GENETIC AND EPIGENETIC EVENTS RESPONSIBLE FOR DEVELOPMENT OF SEVERE AND LETHAL TOXICITY FOLLOWING FLUOROPYRIMIDINES TREATMENT IN ONCOLOGY PATIENTS"@en . "2010-04-06+02:00"^^ . . . " dihydropyrimidinase" . . . "2008-12-31+01:00"^^ . "V\u00FDsledkem projektu jsou nov\u00E9 biologick\u00E9 a klinick\u00E9 informace, kter\u00E9 \u0159e\u0161\u00ED problematiku vztahu toxicity n\u00E1dorov\u00E9 l\u00E9\u010Dby a specifikace genetick\u00FDch a epigenetick\u00FDch faktor\u016F pacienta."@cs .