Clinical implications of thymidylate synthetase, dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferase activity levels in colorectal carcinoma following radical resection and administration of adjuvant 5-FU chemotherapy.
Combination of polymorphisms within 5' and 3' untranslated regions of thymidylate synthase gene modulates survival in 5 fluorouracil-treated colorectal cancer patients.
Combined analysis of genetic polymorphisms in thymidylate synthase, uridine diphosphate glucoronosyltransferase and X-ray cross complementing factor 1 genes as a prognostic factor in advanced colorectal cancer patients treated with 5-fluorouracil plus oxaliplatin or irinotecan.
DPD and TS expressions were measured by reverse transcription-PCR in surgically resected materials of primary colorectal tumors from 37 patients who went on to receive oral treatment of uracil and tegafur and leucovorin for either synchronous or metachronous metastatic diseases.
Immunohistochemical analysis of thymidylate synthase, p16(INK4a), cyclin-dependent kinase 4 and cyclin D1 in colorectal cancers receiving preoperative chemotherapy: significance of p16(INK4a)-mediated cellular arrest as an indicator of chemosensitivity to 5-fluorouracil.
In this study, the mRNA expression levels of these 81 selected genes and the genes of 5-FU-related enzymes, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyltransferase (OPRT), were measured using real-time quantitative RT-PCR assays of surgically resected materials from primary colorectal tumors in 22 patients.
In this study, we investigated the association between both DPD and TS expressions in primary colorectal tumor and the antitumor effect in patients with metastatic colorectal cancer when treated with a fluoropyrimidine-based protocol.
Loss of heterozygosity at the thymidylate synthase (TS) locus on chromosome 18 affects tumor response and survival in individuals heterozygous for a 28-bp polymorphism in the TS gene.
Median gene expression levels of TP and TS did not differ significantly between primary colorectal tumor and corresponding lymph node metastasis but median DPD gene expression levels in the lymph node metastases were significantly higher compared to matched primary colorectal tumors (p=0.015).
Mutations were detected at positions 961 and/or 1031 in the 3'-untranslated regions of the TS gene from the metastases; mutations at these sites were also detected in DNA isolated from normal colon mucosa (n=4) and primary colorectal tumors (n=4).
Polymorphisms in the thymidylate synthase and dihydropyrimidine dehydrogenase genes predict response and toxicity to capecitabine-raltitrexed in colorectal cancer.
Prognostic significance of numeric aberrations of genes for thymidylate synthase, thymidine phosphorylase and dihydrofolate reductase in colorectal cancer.
Single nucleotide polymorphism in the 5' tandem repeat sequences of thymidylate synthase gene predicts for response to fluorouracil-based chemotherapy in advanced colorectal cancer patients.
Studies thus far involving colorectal tumors obtained from patients have focused predominantly on the predictive value of levels of TS expression and p53 mutations in determining response to 5-FU.