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.
With the recognition that TS is an important therapeutic target, direct and specific inhibitors have been developed and are under intensive preclinical and clinical evaluation, primarily in patients with colorectal cancer, with demonstrable activity.
We tested the hypothesis that HSP90 transcriptional and functional inhibition can inhibit cell cycle progression, downregulate TS levels and sensitize colorectal cancer (CRC) cell lines to the effects of 5FU.
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.
We have found that mRNA levels of the E2F family of transcription factors correlates with TS message levels and are higher in lung metastases than in liver metastases of colorectal cancers.
We have determined that the AHL, 3-oxododecanoyl homoserine lactone (3-oxo-C12-(L)-HSL) can down-regulate thymidylate synthase protein at 10 micromol/L and reduce H630 (human colorectal cancer) growth by 50% at 23 micromol/L (IC50) in cell culture.
We found that a combination of germline TS polymorphisms is an independent prognostic marker in selecting CRC patients with worse prognosis, and it may be worthwhile to examine whether these patients would benefit from an alternative therapy.
We found that a combination of germline TS polymorphisms is an independent prognostic marker in selecting CRC patients with worse prognosis, and it may be worthwhile to examine whether these patients would benefit from an alternative therapy.
We designed a nested case-control study within the prospective Physicians' Health Study to investigate whether TS polymorphisms independently predict risk of CRC and simultaneously the overall survival after the disease in the same population.
We aimed to study the expression of TS and Topo I in patients with resected CRC who received adjuvant chemotherapy and correlated it with clinical outcome.
Variants in the dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase and thymidylate synthase genes predict early toxicity of 5-fluorouracil in colorectal cancer patients.
Using a dominant model for the variant allele, several SNPs were significantly associated with CRC including MTHFD1 rs8003379 (OR = 1.65; 95% CI = 1.00-2.73) and rs17824591 (OR = 1.98; 95% CI = 1.14-3.41) and the TYMSrs2853533 SNP (OR = 1.38; 95% CI = 1.05-1.80).
Tumour samples from 73 patients CRC who were treated in advanced stage with either irinotecan alone or in combination with 5-FU/leucovorin, were analysed for expression of TS, hMLH1 and hMSH2 using immunohistochemistry (IHC).
Tumour samples from 73 patients CRC who were treated in advanced stage with either irinotecan alone or in combination with 5-FU/leucovorin, were analysed for expression of TS, hMLH1 and hMSH2 using immunohistochemistry (IHC).
TS mRNA expression was shown to be significantly higher in the pulmonary metastases (mean TS/beta-actin ratio, 19.7; n = 7) as compared with the hepatic metastases (mean TS/beta-actin ratio, 4.7; n = 11) of colorectal cancer.
To address this issue, we studied TSER genotype, TS expression, and activity with specific polymerase chain reaction and activity assays (TS catalytic activity and FdUMP binding) in normal (liver, mucosa) and malignant (primary tumor and liver metastasis) tissues from 83 patients with CRC.
Thymidylate synthase, dihydropyrimidine dehydrogenase, orotate phosphoribosyltransferase mRNA and protein expression levels in solid tumors in large scale population analysis.
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.
This study investigated the effect of surgically induced ischaemia in a xenograft model of a colorectal cancer on the expression of a range of prognostic, predictive, and hypoxic markers, with a particular emphasis on thymidylate synthase.
This study aimed to assess the range of gene copies per nucleus of thymidylate synthase (TYMS), thymidine phosphorylase (TP) and dihydrofolate reductase (DHFR) in colorectal cancer, and to evaluate its prognostic significance following adjuvant chemotherapy, since these enzymes are closely related to efficacy of 5-fluorouracil (5FU).
This meta-analysis suggests that the TSER polymorphism in TS gene but not TS1494del6 polymorphism might be a protective factor for CRC among Caucasian populations.