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Thymidylate synthetase

thymidylate synthase, thymidylate synthetase
Thymidylate synthase catalyzes the methylation of deoxyuridylate to deoxythymidylate using 5,10-methylenetetrahydrofolate (methylene-THF) as a cofactor. This function maintains the dTMP (thymidine-5-prime monophosphate) pool critical for DNA replication and repair. The enzyme has been of interest as a target for cancer chemotherapeutic agents. It is considered to be the primary site of action for 5-fluorouracil, 5-fluoro-2-prime-deoxyuridine, and some folate analogs. Expression of this gene and that of a naturally occuring antisense transcript rTSalpha (GeneID:55556) vary inversely when cell-growth progresses from late-log to plateau phase. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: HAD, CAN, POLYMERASE, dihydrofolate reductase, ERCC1
Papers on thymidylate synthase
B7-H3 increases thymidylate synthase expression via the PI3k-Akt pathway.
Hua et al., Wuxi, China. In Tumour Biol, Feb 2016
Further investigation has revealed elevated expression of thymidylate synthase (TS) and upregulation of the PI3-kinase (PI3K)/Akt pathway in B7-H3 overexpressing cells.
Prognostic significance of thymidylate synthase (TS) expression in cutaneous malignant melanoma.
Ishikawa et al., In Neoplasma, Feb 2016
UNASSIGNED: Thymidylate synthase (TS) plays an essential role in the pathogenesis and development of cancer, and TS-targeting agents have been widely used against different types of cancers.
Biomarkers and prognostic factors for malignant pleural mesothelioma.
Stella et al., Catania, Italy. In Future Oncol, Nov 2015
Finally, thymidylate synthase protein cutoffs may predict mesothelioma response to the association of pemetrexed with a platinum derivative.
Rational selection of predictive pharmacogenomics test for the Fluoropyrimidine/Oxaliplatin based therapy.
Berretta et al., Napoli, Italy. In Eur Rev Med Pharmacol Sci, Nov 2015
MATERIALS AND METHODS: A systematic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted to identify all clinical studies of any association between DPYD and 5-FU correlated to allelic status of 6 validated polymorphisms in five genes Dihydropyrimidine Dehydrogenase (DPYD), Thymidylate Synthase (TYMS), Glutathione S-Transferase (GSTP1), and DNA-repair genes (ERCC2 and XRCC1).
Therapeutic potential of TAS-102 in the treatment of gastrointestinal malignancies.
Peters, Amsterdam, Netherlands. In Ther Adv Med Oncol, Nov 2015
In addition to inhibition of thymidylate synthase, the major mechanism of action of classical fluoropyrimidines, TAS-102's major mechanism of action is incorporation into DNA, thereby causing DNA damage.
TAS-102, a novel antitumor agent: A review of the mechanism of action.
Loupakis et al., Los Angeles, United States. In Cancer Treat Rev, Nov 2015
While both FTD and 5-FU inhibit thymidylate synthase (TS), a central enzyme in DNA synthesis, sufficient TS inhibition by FTD requires continuous infusion; therefore, it is not considered a clinically relevant mechanism with oral dosing.
Inside the biochemical pathways of thymidylate synthase perturbed by anticancer drugs: Novel strategies to overcome cancer chemoresistance.
Costi et al., Modena, Italy. In Drug Resist Updat, Nov 2015
Drugs, which target thymidylate synthase and folate-dependent enzymes, represent an important therapeutic arm in the treatment of various human malignancies.
Pemetrexed Plus Cisplatin Versus Gemcitabine Plus Cisplatin According to Thymidylate Synthase Expression in Nonsquamous Non-Small-Cell Lung Cancer: A Biomarker-Stratified Randomized Phase II Trial.
Ahn et al., Seoul, South Korea. In J Clin Oncol, Sep 2015
PURPOSE: We investigated whether thymidylate synthase (TS) expression is a predictive marker for the clinical outcome of pemetrexed/cisplatin in patients with nonsquamous non-small-cell lung cancer.
The importance of ensemble averaging in enzyme kinetics.
Truhlar et al., Barcelona, Spain. In Acc Chem Res, Mar 2015
Systems discussed include hydride transfer in alcohol dehydrogenase, xylose isomerase, and thymidylate synthase, proton transfer in methylamine dehydrogenase, hydrogen atom transfer in methylmalonyl-CoA mutase, and nucleophilic substitution in haloalkane dehalogenase and two-dimensional potentials of mean force for potentially coupled proton and hydride transfer in the β-oxidation of butyryl-coenzyme A catalyzed by short-chain acyl-CoA dehydrogenase and in the pyruvate to lactate transformation catalyzed by lactate dehydrogenase.
Thymidylate Synthase Polymorphisms and Risk of Lung Cancer among the Jordanian Population: a Case Control Study.
Manasreh et al., Amman, Jordan. In Asian Pac J Cancer Prev, 2014
BACKGROUND: Thymidylate synthase (TS) catalyzes the methylation of deoxyuridylate to deoxythymidylate and is involved in DNA methylation, synthesis and repair.
Correlations between expression levels of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase, and efficacy of 5-fluorouracil-based chemotherapy for advanced colorectal cancer.
Xi et al., Taiyuan, China. In Int J Clin Exp Pathol, 2014
Of these enzymes, thymidylate synthase (TS), thymidine phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD) are known to play important roles in the efficacy of therapeutic agents.
Differences in the efficacy of S-1 monotherapy according to histological type in pretreated patients with advanced non-small cell lung cancer.
Yamamoto et al., Shizuoka, Japan. In Thorac Cancer, 2014
BACKGROUND: S-1 is a novel antimetabolic agent that inhibits thymidylate synthase.
Thymidylate synthase polymorphisms and risk of conotruncal heart defects.
Lammer et al., Austin, United States. In Am J Med Genet A, 2012
observe a 3.6-fold increase in CTD risk among infants who were homozygotes for the 6 bp deletion in the 3'-untranslated region of thymidylate synthase and whose mothers had low folate intake during the peri-conceptional period
Thymidylate synthase (TS) protein expression as a prognostic factor in advanced colorectal cancer: a comparison with TS mRNA expression.
Utsunomiya et al., Tokushima, Japan. In Hepatogastroenterology, 2012
thymidylate synthase(TS) protein expression tends to be related TS mRNA expression and is an independent prognostic factor in advanced colorectal cancer.
Expression of dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase and thymidylate synthase in patients with primary colorectal cancer, and associations with site of first metastasis.
Shirouzu et al., Kurume, Japan. In Anticancer Res, 2012
High expression levels of orotate phosphoribosyl transferase and thymidylate synthase in colorectal cancer appear to be significantly involved in metastasis after curative surgery
Expression levels of thymidylate synthase, dihydropyrimidine dehydrogenase, and thymidine phosphorylase in patients with colorectal cancer.
Hibi et al., Yokohama, Japan. In Anticancer Res, 2012
mRNA expression of TYMS, DPYD, and TYMP is associated with distinct characteristics and may be useful for predicting survival in patients with stage IV colorectal cancer.
Association of thymidylate synthase and hypoxia inducible factor-1alpha DNA polymorphisms with pancreatic cancer.
Gamallo et al., Alacant, Spain. In Tumori, 2012
The variant del14946bp allele within the thymidylate synthase gene single nucelotide polymorphism were associated with the development of pancreatic cancer.
Phase II trial of pemetrexed and bevacizumab in patients with recurrent or metastatic head and neck cancer.
Romkes et al., Pittsburgh, United States. In J Clin Oncol, 2011
DNA was isolated from whole blood samples for the detection of polymorphisms in thymidylate synthase, methylenetetrahydrofolate reductase (MTHFR), and VEGF.
Thymidylate synthase genotype-directed neoadjuvant chemoradiation for patients with rectal adenocarcinoma.
McLeod et al., Saint Louis, United States. In J Clin Oncol, 2011
Polymorphisms in the thymidylate synthase gene (TYMS) had previously defined two risk groups associated with disparate tumor DS rates (60% v 22%).
Multicenter phase II trial of S-1 in patients with cytokine-refractory metastatic renal cell carcinoma.
Akaza et al., Fukuoka, Japan. In J Clin Oncol, 2011
The expression level of thymidylate synthase (TS) mRNA was significantly lower in patients who responded to treatment (t-test, P = .048),
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