1,721,005 research outputs found
G>C SNP of thymidylate synthase with respect to colorectal cancer.Pharmacogenomics. 2007 Aug;8(8):985-96.PMID: 17716232
No full textSeveral studies indicate that low thymidylate synthase (TS) protein levels in tumor and normal tissues of colorectal cancer patients are associated with better clinical response to fluorouracil-based chemotherapy and higher risk of toxicity. However no correlation or even reverse correlation has also been reported. These conflicting results may be partly due to the methodological limitations of the immunohistochemical techniques generally used to quantify thymidylate synthase expression. In this sense, a genetic approach aiming at determining the influence of the TS gene polymorphisms on clinical outcome seems more appealing. So far three polymorphisms have been identified and studied in the TYMS gene: the variable number of 28-bp tandem repeats (2R or 3R) in the 5'UTR; the G > C substitution at the 12th nucleoticle in the second repeat of the 3R allele (3RG > 3RC) and the 6-bp deletion in the 3'UTR (+6bp/-6bp 3'UTR). In vitro studies indicate that each of these polymorphisms can influence thymidylate synthase expression. In particular, the G > C SNIP, which alters the E-box sequence binding an upstream stimulatory factor (USF-1), seems more important than the variable number of tandem repeats in determining TS gene expression in that the 3RC allele has a reduced translational activity compared with the 3RG allele, while showing the same activity as the 2R allele. In contrast with the in vitro findings, the clinical studies in colorectal patients failed to find a consistent relationship between the G > C polymorphism and clinical outcome measures (response, survival or toxicity). This discrepancy may be due to methodological heterogeneities amongst the studies, including genotyping in normal or tumor tissues, loss of heterozygosity in tumor cells not evaluated, variable doses and schedules of fluorouracil-based therapy, and variable tumor stage. The complexity of TYMS gene regulation, and the possibility that other polymorphisms may contribute to fluorouracil response, call for further studies before TYMS genotyping can be used in clinical practice to select colorectal cancer patients who are most likely to benefit from chemotherapy
A new limited sampling strategy for 5-fluorouracil AUC determination following rapid i.v. bolus
No full textI.F. 2.1
A novel G/C single-nucleotide polymorphism in the double 28-bp repeat thymidylate synthase allele
No full text
Relationships between bioelectrical impedance parameters and fluorouracil pharmacokinetics
No full textI.F. 2.21
Frequency of uridine monophosphate synthase Gly(213)Ala polymorphism in Caucasian gastrointestinal cancer patients and healthy subjects, investigated by means of new, rapid genotyping assays
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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