Thymidylate synthase and microsatellite instability in colorectal cancer: implications for disease free survival, treatment response and survival with metastases.
The TS genotype of 68 patients with colorectal cancer was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis in peripheral blood mononuclear cells and tumour tissue.
Thymidylate synthase expression pattern, expression level and single nucleotide polymorphism are predictors for disease-free survival in patients of colorectal cancer treated with 5-fluorouracil.
Long Survival and Severe Toxicity Under 5-Fluorouracil-Based Therapy in a Patient With Colorectal Cancer Who Harbors a Germline Codon-Stop Mutation in TYMS.
Thymidylate synthase (TS) is the target enzyme for 5-fluorouracil (5-FU), and TS expression may determine clinical response and survival after therapy with 5-FU in colorectal cancer.
Expression of thymidylate synthase (TS) and the 5-fluorouracil (5-FU) metabolic enzymes, including dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT), thymidine phosphorylase (TP), and uridine phosphorylase (UP), has been reported to be associated with the sensitivity to 5-FU-based chemotherapy in colorectal cancer.
Our data suggest that genotyping patients for the thymidylate synthase polymorphism would be useful in identifying patients who are more likely to respond to capecitabine treatment for advanced colorectal cancer.
The result suggests that mRNA translation is responsible for the genotype-dependent difference of TS protein expression, as is consistent with our previous observation in colorectal cancer.
Melatonin may serve as a potential therapeutic option on its own, or in conjunction with 5-FU, in the treatment of patients with advanced or chemoresistant CRC.Melatonin inhibits the growth of 5-FU resistant colorectal cancer (CRC) cells through upregulation of miR-215-5p and a concomitant downregulation of TYMS.
In this study, primary tumors obtained from 1,129 patients with colorectal cancer were used to measure the mRNA expression levels of the following genes associated with the effects of standard chemotherapy for colorectal cancer: 5-fluorouracil (5-FU)-related thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD) and thymidine phosphorylase (TYMP); folate-related dihydrofolate reductase (DHFR), folylpolyglutamate synthase (FPGS) and gamma-glutamyl hydrolase (GGH); irinotecan-related topoisomerase I (TOP1); oxaliplatin-related excision repair cross-complementing 1 (ERCC1); biologic agent-related vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR).
In this study, therefore, we examined the effect of a combination of TS silencing by an RNA interfering molecule, chemically synthesized short hairpin RNA against TS (shTS), and 5-FU on the growth of human colorectal cancer cell (DLD-1) both in vitro and in vivo.
Floxuridine (5'-fluorodeoxyuridine, FUdR) acts as an inhibitor of DNA replication by binding to thymidylate synthase and is widely used to treat colorectal cancer.
Dihydropyrimidine dehydrogenase and thymidylate synthase polymorphisms and their association with 5-fluorouracil/leucovorin chemotherapy in colorectal cancer.
This study suggests that common genetic variation in MTHFR but not TYMS may be useful for predicting toxicity from capecitabine in patients with advanced colorectal cancer.
Correlations to histopathological parameters and clinical follow-up revealed an association of TP, DPD and TS mRNA expression patterns with tumor stage and suggested new prognostic and predictive markers for patients with colorectal cancer.
Combination of polymorphisms within 5' and 3' untranslated regions of thymidylate synthase gene modulates survival in 5 fluorouracil-treated colorectal cancer patients.