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Statements

Subject Item
n2:RIV%2F00179906%3A_____%2F12%3A10133953%21RIV13-MZ0-00179906
rdf:type
n10:Vysledek skos:Concept
rdfs:seeAlso
http://www.lfhk.cuni.cz/Data/files/Casopisy/2012/2012_153.pdf
dcterms:description
The colorectal cancer ranks high among the malignant tumours in incidence and mortality and irinotecan is standardly used in palliative treatment of metastatic disease in every therapeutic line. Unfortunately, the treatment with irinotecan is often associated with severe toxicities, especially neutropenia and diarrhea. The majority of the toxic manifestation is caused by the insufficient deactivation (glucuronidation) of irinotecan active metabolite SN-38 by UGT1A enzyme. The elevated SN-38 plasma concentration is responsible for the hematological and gastrointestinal toxicity that can become life-threatening. The patients carrying the mutation of the gene encoding UGT1A enzyme lack the ability of bilirubin glucuronidation, and suffer from the inherited un-conjugated hyperbilirubinemia (Gilbert syndrome, Crigler-Najjar type 1 and 2 syndrome). The mutations in other enzyme systems also play role in the etiopathogenesis of the irinotecan toxicity: CYP3A (cytochrome P-450), ABC family of transmembrane transporters (adenosine-triphosphate binding cassette). The goal of the contemporary research is to determine the predictive factors that will enable the individual adjustment of the individual drug dosage while minimising the adverse effects and maintaining the treatment benefit. The colorectal cancer ranks high among the malignant tumours in incidence and mortality and irinotecan is standardly used in palliative treatment of metastatic disease in every therapeutic line. Unfortunately, the treatment with irinotecan is often associated with severe toxicities, especially neutropenia and diarrhea. The majority of the toxic manifestation is caused by the insufficient deactivation (glucuronidation) of irinotecan active metabolite SN-38 by UGT1A enzyme. The elevated SN-38 plasma concentration is responsible for the hematological and gastrointestinal toxicity that can become life-threatening. The patients carrying the mutation of the gene encoding UGT1A enzyme lack the ability of bilirubin glucuronidation, and suffer from the inherited un-conjugated hyperbilirubinemia (Gilbert syndrome, Crigler-Najjar type 1 and 2 syndrome). The mutations in other enzyme systems also play role in the etiopathogenesis of the irinotecan toxicity: CYP3A (cytochrome P-450), ABC family of transmembrane transporters (adenosine-triphosphate binding cassette). The goal of the contemporary research is to determine the predictive factors that will enable the individual adjustment of the individual drug dosage while minimising the adverse effects and maintaining the treatment benefit.
dcterms:title
Predictors of Irinotecan Toxicity and Efficacy in Treatment of Metastatic Colorectal Cancer Predictors of Irinotecan Toxicity and Efficacy in Treatment of Metastatic Colorectal Cancer
skos:prefLabel
Predictors of Irinotecan Toxicity and Efficacy in Treatment of Metastatic Colorectal Cancer Predictors of Irinotecan Toxicity and Efficacy in Treatment of Metastatic Colorectal Cancer
skos:notation
RIV/00179906:_____/12:10133953!RIV13-MZ0-00179906
n10:predkladatel
n12:ico%3A00179906
n3:aktivita
n13:I
n3:aktivity
I
n3:cisloPeriodika
4
n3:dodaniDat
n11:2013
n3:domaciTvurceVysledku
n4:5448379 n4:5460913 n4:9990801
n3:druhVysledku
n14:J
n3:duvernostUdaju
n16:S
n3:entitaPredkladatele
n15:predkladatel
n3:idSjednocenehoVysledku
161064
n3:idVysledku
RIV/00179906:_____/12:10133953
n3:jazykVysledku
n6:eng
n3:klicovaSlova
Diarrhea; Neutropenia; Pharmacogenetics; UGT1A1*28; SN-38; Irinotecan
n3:klicoveSlovo
n8:SN-38 n8:UGT1A1%2A28 n8:Diarrhea n8:Neutropenia n8:Irinotecan n8:Pharmacogenetics
n3:kodStatuVydavatele
CZ - Česká republika
n3:kontrolniKodProRIV
[8698CDC4FD19]
n3:nazevZdroje
Acta medica (Hradec Králové) / Universitas Carolina, Facultas Medica Hradec Kralove
n3:obor
n18:FD
n3:pocetDomacichTvurcuVysledku
3
n3:pocetTvurcuVysledku
3
n3:rokUplatneniVysledku
n11:2012
n3:svazekPeriodika
55
n3:tvurceVysledku
Paulík, Adam Filip, Stanislav Grim, Jiří
s:issn
1211-4286
s:numberOfPages
7