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.
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.
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.
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.
Overall, our data indicate that miR-203 enhances 5-FU chemosensitivity via the downregulation of TYMS in colorectal cancer and provide important insight into the mechanism of 5-FU resistance in colorectal cancer patients.
Notably, cobimetinib appeared to enhance the efficacy of 5-fluorouracil (5-FU) by decreasing TYMS expression, high expression of which is responsible for 5-FU resistance in colorectal cancer.
In this study, TS mRNA expression was examined in primary tumor and normal tissues from 76 patients with high- risk stage II/III colorectal cancer by laser capture microdissection and polymerase chain reaction.
The Oncologist 2017;22:107-114Implications for Practice: This study finds that measurement of tumor levels of thymidylate synthase is not helpful in assigning specific adjuvant treatment for colorectal cancer.
Danenberg tumor profile method (DTP) was used in order to measure mRNA expression levels of thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), and thymidine phosphorylase (TYMP) from 180 patients with colorectal cancer.
MSI in five reference loci, MMR enzymes (hMSH2, hMSH6, hMLH1 and hPMS2), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression were assessed in paraffin embedded tumor specimens, and associated with outcome in 340 consecutive patients completely resected for colorectal cancer stages II-IV and subsequently receiving adjuvant 5-fluorouracil therapy.
Lack of correlation between immunohistochemical expression of E2F-1, thymidylate synthase expression and clinical response to 5-fluorouracil in advanced colorectal cancer.
ZD9331, a highly specific TS inhibitor that dose not require polyglutamation for its activation, has shown activity in patients with refractory ovarian and colorectal cancer.
Associations between polymorphisms in the thymidylate synthase gene, the expression of thymidylate synthase mRNA and the microsatellite instability phenotype of colorectal cancer.
The aim of the present study has been to verify the predictive value of immunohistochemical topoisomerase-I (Topo-I) and TS primary tumour expression in a consecutive series of 62 advanced colorectal cancer patients that received a first line 5-FU/CPT-11 chemotherapy.
Long noncoding RNA XIST is a prognostic factor in colorectal cancer and inhibits 5-fluorouracil-induced cell cytotoxicity through promoting thymidylate synthase expression.
We have shown previously that metastatic tumors of human colorectal cancer in lung as compared to liver have high levels of thymidylate synthase (TS) mRNA expression that correlated with high levels of E2F-1 mRNA expression.
The effect of this polymorphism on the expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT) and thymidine phosphorylase (TP) in colorectal cancer was investigated.