Matches in SemOpenAlex for { <https://semopenalex.org/work/W2262306620> ?p ?o ?g. }
Showing items 1 to 82 of
82
with 100 items per page.
- W2262306620 endingPage "14572" @default.
- W2262306620 startingPage "14572" @default.
- W2262306620 abstract "14572 Background: Carbonyl reductases are ubiquitously expressed monomeric NADPH dependent cytosolic enzymes which catalyze reduction of chemically diverse substrates. The study aimed to identify polymorphisms in the gene encoding carbonyl reductase 1 (CBR1) and investigate their influence on doxorubicin disposition. Methods: Patients (N=62) with histologically confirmed invasive breast cancer (Stage I-III) receiving adjuvant chemotherapy were recruited. Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) were administered every 3 weeks for 4–6 cycles. Genomic DNA was isolated from peripheral blood for direct sequencing. Doxorubicin pharmacokinetic parameters were estimated using noncompartmental analysis (WinNonlin) and Mann-Whitney U test was used to assess genotypic-phenotypic correlations. Results: Four CBR1 polymorphisms (-48G>A, c.219G>C, c.627C>T, +967G>A) were identified. Moderate degree of linkage between the c.219G>C, c.627C>T and +967G>A polymorphisms [ID’I>0.7 in all groups] were observed. Major CBR1 haplotypes (>5%) [G-C-G,C-T-A,C-T-G] had a cumulative frequency of 83%. Sequence clustering using complete linkage algorithm identified 2 major groups (D1 and D2) among the 12 CBR1 diplotypes. Patients in the D1 diplotype group had significantly higher clearance [CL/BSA(Lh-1m-2), median: 25.09; range:16.44–55.66] and significantly lower exposure levels of doxorubicin [AUC0-∞/dose/BSA (hm-5):median:15.08;range:6.18–38.03] compared to patients belonging to the D2 diplotype group [CL/BSA(Lh-1m-2), median:20.88;range:8.68–31.79,(P=0.014) and AUC0-∞/dose/BSA(hm-5):median: 21.35; range:9.82–67.17,(P=0.007), respectively]. Patients harboring the D1 diplotype family had lower exposure levels of doxorubicinol [AUC0-∞/dose/BSA (hm- 5): median:8.99; range:3.68–20.63] when compared to patients belonging to the D2 [AUC0- ∞/dose/BSA(hm-5):median:11.28;range:6.25–18.71,P=0.057] diplotype family. Conclusion: The CBR1 D2 diplotypes correlate with significantly higher exposure levels of doxorubicin suggesting lowered intracellular conversion to doxorubicinol in these patients which may predispose them to greater toxicity. No significant financial relationships to disclose." @default.
- W2262306620 created "2016-06-24" @default.
- W2262306620 creator A5010714400 @default.
- W2262306620 creator A5019107660 @default.
- W2262306620 creator A5031180394 @default.
- W2262306620 creator A5031518835 @default.
- W2262306620 creator A5034059147 @default.
- W2262306620 creator A5051566309 @default.
- W2262306620 creator A5068546735 @default.
- W2262306620 creator A5071731093 @default.
- W2262306620 date "2008-05-20" @default.
- W2262306620 modified "2023-09-26" @default.
- W2262306620 title "Carbonyl reductase 1 polymorphisms: Influence of diplotype structures on doxorubicin disposition in Asian breast cancer patients" @default.
- W2262306620 doi "https://doi.org/10.1200/jco.2008.26.15_suppl.14572" @default.
- W2262306620 hasPublicationYear "2008" @default.
- W2262306620 type Work @default.
- W2262306620 sameAs 2262306620 @default.
- W2262306620 citedByCount "0" @default.
- W2262306620 crossrefType "journal-article" @default.
- W2262306620 hasAuthorship W2262306620A5010714400 @default.
- W2262306620 hasAuthorship W2262306620A5019107660 @default.
- W2262306620 hasAuthorship W2262306620A5031180394 @default.
- W2262306620 hasAuthorship W2262306620A5031518835 @default.
- W2262306620 hasAuthorship W2262306620A5034059147 @default.
- W2262306620 hasAuthorship W2262306620A5051566309 @default.
- W2262306620 hasAuthorship W2262306620A5068546735 @default.
- W2262306620 hasAuthorship W2262306620A5071731093 @default.
- W2262306620 hasConcept C104317684 @default.
- W2262306620 hasConcept C121608353 @default.
- W2262306620 hasConcept C126322002 @default.
- W2262306620 hasConcept C134651460 @default.
- W2262306620 hasConcept C135763542 @default.
- W2262306620 hasConcept C181199279 @default.
- W2262306620 hasConcept C197754878 @default.
- W2262306620 hasConcept C2776694085 @default.
- W2262306620 hasConcept C2776755627 @default.
- W2262306620 hasConcept C2781303535 @default.
- W2262306620 hasConcept C530470458 @default.
- W2262306620 hasConcept C54355233 @default.
- W2262306620 hasConcept C55493867 @default.
- W2262306620 hasConcept C71924100 @default.
- W2262306620 hasConcept C86803240 @default.
- W2262306620 hasConcept C90924648 @default.
- W2262306620 hasConcept C98274493 @default.
- W2262306620 hasConceptScore W2262306620C104317684 @default.
- W2262306620 hasConceptScore W2262306620C121608353 @default.
- W2262306620 hasConceptScore W2262306620C126322002 @default.
- W2262306620 hasConceptScore W2262306620C134651460 @default.
- W2262306620 hasConceptScore W2262306620C135763542 @default.
- W2262306620 hasConceptScore W2262306620C181199279 @default.
- W2262306620 hasConceptScore W2262306620C197754878 @default.
- W2262306620 hasConceptScore W2262306620C2776694085 @default.
- W2262306620 hasConceptScore W2262306620C2776755627 @default.
- W2262306620 hasConceptScore W2262306620C2781303535 @default.
- W2262306620 hasConceptScore W2262306620C530470458 @default.
- W2262306620 hasConceptScore W2262306620C54355233 @default.
- W2262306620 hasConceptScore W2262306620C55493867 @default.
- W2262306620 hasConceptScore W2262306620C71924100 @default.
- W2262306620 hasConceptScore W2262306620C86803240 @default.
- W2262306620 hasConceptScore W2262306620C90924648 @default.
- W2262306620 hasConceptScore W2262306620C98274493 @default.
- W2262306620 hasIssue "15_suppl" @default.
- W2262306620 hasLocation W22623066201 @default.
- W2262306620 hasOpenAccess W2262306620 @default.
- W2262306620 hasPrimaryLocation W22623066201 @default.
- W2262306620 hasRelatedWork W2084681273 @default.
- W2262306620 hasRelatedWork W2112946603 @default.
- W2262306620 hasRelatedWork W2165933909 @default.
- W2262306620 hasRelatedWork W2171127432 @default.
- W2262306620 hasRelatedWork W2298028778 @default.
- W2262306620 hasRelatedWork W2365277249 @default.
- W2262306620 hasRelatedWork W2380201224 @default.
- W2262306620 hasRelatedWork W2413498044 @default.
- W2262306620 hasRelatedWork W2579622845 @default.
- W2262306620 hasRelatedWork W4214554217 @default.
- W2262306620 hasVolume "26" @default.
- W2262306620 isParatext "false" @default.
- W2262306620 isRetracted "false" @default.
- W2262306620 magId "2262306620" @default.
- W2262306620 workType "article" @default.