TYMS

Summary

Gene Symbol: TYMS
Description: thymidylate synthetase
Alias: HST422, TMS, thymidylate synthase, TSase
Species: human
Products:     TYMS

Top Publications

  1. Braun M, Richman S, Thompson L, Daly C, Meade A, Adlard J, et al. Association of molecular markers with toxicity outcomes in a randomized trial of chemotherapy for advanced colorectal cancer: the FOCUS trial. J Clin Oncol. 2009;27:5519-28 pubmed publisher
    ..Ten polymorphisms were assessed: thymidylate synthase-enhancer region (TYMS-ER), thymidylate synthase 1494 (TYMS-1494), dihydropyrimidine dehydrogenase (DPYD), ..
  2. Largillier R, Etienne Grimaldi M, Formento J, Ciccolini J, Nebbia J, Ginot A, et al. Pharmacogenetics of capecitabine in advanced breast cancer patients. Clin Cancer Res. 2006;12:5496-502 pubmed
    ..polymorphisms may potentially influence pharmacodynamics of fluoropyrimidines, including capecitabine, are thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and dihydropyrimidine dehydrogenase (DPD)...
  3. Kornmann M, Schwabe W, Sander S, Kron M, Strater J, Polat S, et al. Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression levels: predictors for survival in colorectal cancer patients receiving adjuvant 5-fluorouracil. Clin Cancer Res. 2003;9:4116-24 pubmed
    ..In this study, we determined the prognostic value of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression in colorectal cancer patients treated with ..
  4. Kumagai K, Hiyama K, Oyama T, Maeda H, Kohno N. Polymorphisms in the thymidylate synthase and methylenetetrahydrofolate reductase genes and sensitivity to the low-dose methotrexate therapy in patients with rheumatoid arthritis. Int J Mol Med. 2003;11:593-600 pubmed
    ..b>Thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) are key enzymes in the folate metabolism and both have ..
  5. Phan J, Koli S, Minor W, Dunlap R, Berger S, Lebioda L. Human thymidylate synthase is in the closed conformation when complexed with dUMP and raltitrexed, an antifolate drug. Biochemistry. 2001;40:1897-902 pubmed
    b>Thymidylate synthase (TS) is a major target in the chemotherapy of colorectal cancer and some other neoplasms while raltitrexed (Tomudex, ZD1694) is an antifolate inhibitor of TS approved for clinical use in several European countries...
  6. Phan J, Steadman D, Koli S, Ding W, Minor W, Dunlap R, et al. Structure of human thymidylate synthase suggests advantages of chemotherapy with noncompetitive inhibitors. J Biol Chem. 2001;276:14170-7 pubmed
    b>Thymidylate synthase (TS) is a major target in the chemotherapy of colorectal cancer and some other neoplasms...
  7. Trinh B, Ong C, Coetzee G, Yu M, Laird P. Thymidylate synthase: a novel genetic determinant of plasma homocysteine and folate levels. Hum Genet. 2002;111:299-302 pubmed
    The thymidylate synthase gene ( TYMS or TS) encodes a tightly regulated enzyme that catalyzes the conversion of deoxyuridylate to thymidylate, and contains a tandem repeat polymorphism that affects expression of the enzyme...
  8. Duzgun N, Duman T, Morris Y, Tutkak H, Kose K, Ertugrul E, et al. Thymidylate synthase genotype and serum concentrations of homocysteine and folate in Behçet's disease. Clin Rheumatol. 2008;27:1221-5 pubmed publisher
    The aim of this study was to assess whether thymidylate synthase (TYMS) genotype, serum homocysteine, and folate concentrations were related to venous thrombosis in Behçet's disease (BD) patients...
  9. Liu J, Schmitz J, Lin X, Tai N, Yan W, Farrell M, et al. Thymidylate synthase as a translational regulator of cellular gene expression. Biochim Biophys Acta. 2002;1587:174-82 pubmed
    Studies from our laboratory have shown that the folate-dependent enzyme, thymidylate synthase (TS), functions as an RNA binding protein...

More Information

Publications129 found, 100 shown here

  1. Tan W, Miao X, Wang L, Yu C, Xiong P, Liang G, et al. Significant increase in risk of gastroesophageal cancer is associated with interaction between promoter polymorphisms in thymidylate synthase and serum folate status. Carcinogenesis. 2005;26:1430-5 pubmed
    b>Thymidylate synthase (TS) catalyzes the 5,10-methylene-tetrahydrofolate-mediated conversion of deoxyuridine monophosphate to deoxythymydine monophosphate, a nucleotide required for DNA synthesis and repair...
  2. Henríquez Hernández L, Pérez L, Hernández A, de León A, Díaz Chico B, Rosales A. TYMS, MTHFR, p53 and MDR1 gene polymorphisms in breast cancer patients treated with adjuvant therapy. Cancer Epidemiol. 2010;34:490-3 pubmed publisher
    The distribution of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms was investigated in 80 consecutive breast cancer patients treated with adjuvant chemotherapy...
  3. Matsuo K, Ito H, Wakai K, Hirose K, Saito T, Suzuki T, et al. One-carbon metabolism related gene polymorphisms interact with alcohol drinking to influence the risk of colorectal cancer in Japan. Carcinogenesis. 2005;26:2164-71 pubmed
    ..genes for methylenetetrahydrofolate reductase), MTR A2756G (gene for methionine synthase) and TS (gene for thymidylate synthase) tandem repeats polymorphisms, have attracted attention...
  4. Curtin K, Ulrich C, Samowitz W, Bigler J, Caan B, Potter J, et al. Thymidylate synthase polymorphisms and colon cancer: associations with tumor stage, tumor characteristics and survival. Int J Cancer. 2007;120:2226-32 pubmed
    b>Thymidylate synthase (TS) is a key enzyme in folate metabolism, a pathway that is important in colorectal carcinogenesis...
  5. Ranganathan P, Culverhouse R, Marsh S, Mody A, Scott Horton T, Brasington R, et al. Methotrexate (MTX) pathway gene polymorphisms and their effects on MTX toxicity in Caucasian and African American patients with rheumatoid arthritis. J Rheumatol. 2008;35:572-9 pubmed
    ..C1 (ABCC1), C2 (ABCC2), folylpolyglutamyl synthase (FPGS), methylenetetrahydrofolate reductase (MTHFR), and thymidylate synthase (TYMS). Both cohorts included Caucasian Americans and African Americans...
  6. Ruzzo A, Graziano F, Kawakami K, Watanabe G, Santini D, Catalano V, et al. Pharmacogenetic profiling and clinical outcome of patients with advanced gastric cancer treated with palliative chemotherapy. J Clin Oncol. 2006;24:1883-91 pubmed
    ..Specific polymorphisms may influence clinical outcomes of AGC patients. Selecting palliative chemotherapy on the basis of pretreatment genotyping may represent an innovative strategy that warrants prospective studies. ..
  7. Hu H, Kuang L, Zeng X, Li B, Liu E, Zhong M. Predictive value of thymidylate synthase expression in gastric cancer: a systematic review with meta-analysis. Asian Pac J Cancer Prev. 2012;13:261-7 pubmed
    The relationship between thymidylate synthase (TS) expression and outcomes in gastric cancer (GC) patients remains controversial, although most studies reported poor survival and reduced response to fluoropyrimidine were related to high ..
  8. Mandola M, Stoehlmacher J, Zhang W, Groshen S, Yu M, Iqbal S, et al. A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels. Pharmacogenetics. 2004;14:319-27 pubmed
    A 6 bp deletion polymorphism in the thymidylate synthase (TS) gene was investigated in order to determine its function. A luciferase system was used to investigate the function of the 6 bp/1494 polymorphism in vitro...
  9. Kaira K, Ohde Y, Nakagawa K, Okumura T, Murakami H, Takahashi T, et al. Thymidylate synthase expression is closely associated with outcome in patients with pulmonary adenocarcinoma. Med Oncol. 2012;29:1663-72 pubmed publisher
    The aim of this study is to elucidate the prognostic significance of thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT) and dihydropyrimidine dehydrogenase (DPD) in completely resected non-small cell lung cancer (NSCLC)...
  10. Nicolson M, Fennell D, Ferry D, O Byrne K, Shah R, Potter V, et al. Thymidylate synthase expression and outcome of patients receiving pemetrexed for advanced nonsquamous non-small-cell lung cancer in a prospective blinded assessment phase II clinical trial. J Thorac Oncol. 2013;8:930-9 pubmed publisher
    ..retrospective analyses of patients with nonsquamous non-small-cell lung cancer treated with pemetrexed, low thymidylate synthase (TS) expression is associated with better clinical outcomes...
  11. Lu J, Gao C, Wu J, Cao H, Tajima K, Feng J. Polymorphism in the 3'-untranslated region of the thymidylate synthase gene and sensitivity of stomach cancer to fluoropyrimidine-based chemotherapy. J Hum Genet. 2006;51:155-60 pubmed
    To investigate the relationship between polymorphism in the 3'-untranslated region (3'-UTR) of the thymidylate synthase (TS) gene and sensitivity of gastric cancer to 5-fluorouracil (5-FU)-based chemotherapy, 106 cases of advanced gastric ..
  12. Park D, Stoehlmacher J, Zhang W, Tsao Wei D, Groshen S, Lenz H. Thymidylate synthase gene polymorphism predicts response to capecitabine in advanced colorectal cancer. Int J Colorectal Dis. 2002;17:46-9 pubmed
    b>Thymidylate synthase is a target enzyme for chemotherapeutic agents such as 5-fluorouracil and capecitabine, its oral prodrug...
  13. Smit E, Burgers S, Biesma B, Smit H, Eppinga P, Dingemans A, et al. Randomized phase II and pharmacogenetic study of pemetrexed compared with pemetrexed plus carboplatin in pretreated patients with advanced non-small-cell lung cancer. J Clin Oncol. 2009;27:2038-45 pubmed publisher
    ..05, two-sided log-rank test). Polymorphisms of thymidylate synthase, the reduced folate carrier, gamma-glutamyl hydrolase, and methylenetetrahydrofolate reductase (MTHF) were ..
  14. Grimminger P, Schneider P, Metzger R, Vallbohmer D, Holscher A, Danenberg P, et al. Low thymidylate synthase, thymidine phosphorylase, and dihydropyrimidine dehydrogenase mRNA expression correlate with prolonged survival in resected non-small-cell lung cancer. Clin Lung Cancer. 2010;11:328-34 pubmed publisher
    b>Thymidylate synthase (TS), thymidine phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD) are key enzymes in the 5-fluorouracil (5-FU) pathway...
  15. Shaw G, Lu W, Zhu H, Yang W, Briggs F, Carmichael S, et al. 118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects. BMC Med Genet. 2009;10:49 pubmed publisher
    ..5-5.9); MTRR (rs10380) OR = 3.4 (1.6-7.1); MTRR (rs1801394) OR = 0.7 (0.5-0.9); MTRR (rs9332) OR = 2.7 (1.3-5.3); TYMS (rs2847149) OR = 2.2 (1.4-3.5); TYMS (rs1001761) OR = 2.4 (1.5-3.8); and TYMS (rs502396) OR = 2.1 (1.3-3.3)...
  16. Wang X, Wang Y, Wang Y, Cheng J, Wang Y, Ha M. Association of thymidylate synthase gene 3'-untranslated region polymorphism with sensitivity of non-small cell lung cancer to pemetrexed treatment: TS gene polymorphism and pemetrexed sensitivity in NSCLC. J Biomed Sci. 2013;20:5 pubmed publisher
    b>Thymidylate synthase (TS) is a key enzyme responsible for DNA synthesis and repair. Altered expression of TS protein or TS gene polymorphisms has been associated with cancer progression and treatment response...
  17. Wang J, Wang B, Bi J, Di J. The association between two polymorphisms in the TYMS gene and breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 2011;128:203-9 pubmed publisher
    b>Thymidylate synthase (TYMS), which catalyzes the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate, is a central enzyme in the folate metabolic pathway...
  18. Huang Z, Hua D, Li L. The polymorphisms of TS and MTHFR predict survival of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population. Cancer Chemother Pharmacol. 2009;63:911-8 pubmed publisher
    The aim of this study was to investigate the association of the thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) polymorphisms with the clinical outcomes of gastric cancer patients treated with 5-FU-based adjuvant ..
  19. Kawate H, Landis D, Loeb L. Distribution of mutations in human thymidylate synthase yielding resistance to 5-fluorodeoxyuridine. J Biol Chem. 2002;277:36304-11 pubmed
    b>Thymidylate synthase (TS) catalyzes methylation of dUMP to dTMP and is the target of cancer chemotherapeutic agents (e.g. 5-fluorouracil)...
  20. Ishida Y, Kawakami K, Tanaka Y, Kanehira E, Omura K, Watanabe G. Association of thymidylate synthase gene polymorphism with its mRNA and protein expression and with prognosis in gastric cancer. Anticancer Res. 2002;22:2805-9 pubmed
    b>Thymidylate synthase (TS) is a target enzyme of 5-fluorouracil (5-FU). TS has a polymorphic repeated sequence in the 5'-UTR and the polymorphism is associated with TS protein expression...
  21. Dervieux T, Furst D, Lein D, Capps R, Smith K, Walsh M, et al. Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum. 2004;50:2766-74 pubmed
    ..MTXPGs) and inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC) and thymidylate synthase (TS)...
  22. Zhai X, Gao J, Hu Z, Tang J, Qin J, Wang S, et al. Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis. BMC Cancer. 2006;6:138 pubmed
    ..b>Thymidylate synthase (TYMS) is a key enzyme that participates in folate metabolism and catalyzes the conversion of dUMP to dTMP ..
  23. Lecomte T, Ferraz J, Zinzindohoue F, Loriot M, Tregouet D, Landi B, et al. Thymidylate synthase gene polymorphism predicts toxicity in colorectal cancer patients receiving 5-fluorouracil-based chemotherapy. Clin Cancer Res. 2004;10:5880-8 pubmed
    The target enzyme for 5-fluorouracil (5-FU) is thymidylate synthase (TS)...
  24. Krajinovic M, Costea I, Chiasson S. Polymorphism of the thymidylate synthase gene and outcome of acute lymphoblastic leukaemia. Lancet. 2002;359:1033-4 pubmed
    Interindividual variability in response to methotrexate could be caused by variable concentrations of thymidylate synthase. We investigated the possible association between a tandem-repeat polymorphism in the thymidylate synthase promoter,..
  25. Zhang Z, Xu Y, Zhou J, Wang X, Wang L, Hu X, et al. Polymorphisms of thymidylate synthase in the 5'- and 3'-untranslated regions associated with risk of gastric cancer in South China: a case-control analysis. Carcinogenesis. 2005;26:1764-9 pubmed
    ..We hypothesized that the polymorphisms of thymidylate synthase (TYMS) gene involved in folate metabolism are associated with GC risk...
  26. Farrugia D, Ford H, Cunningham D, Danenberg K, Danenberg P, Brabender J, et al. Thymidylate synthase expression in advanced colorectal cancer predicts for response to raltitrexed. Clin Cancer Res. 2003;9:792-801 pubmed
    The purpose of this research was to evaluate the predictive value of expression of thymidylate synthase (TS) and other genes for response to raltitrexed (RTX)...
  27. Mannava S, Grachtchouk V, Wheeler L, Im M, Zhuang D, Slavina E, et al. Direct role of nucleotide metabolism in C-MYC-dependent proliferation of melanoma cells. Cell Cycle. 2008;7:2392-400 pubmed
    ..These included thymidylate synthase (TS), inosine monophosphate dehydrogenase 2 (IMPDH2) and phosphoribosyl pyrophosphate synthetase 2 (PRPS2)...
  28. Yim D, Kim O, An H, Kang H, Ahn D, Hwang S, et al. Polymorphisms of thymidylate synthase gene 5'- and 3'-untranslated region and risk of gastric cancer in Koreans. Anticancer Res. 2010;30:2325-30 pubmed
    b>Thymidylate synthase (TS) plays an important role in the conversion of dUMP to dTMP...
  29. Afzal S, Gusella M, Jensen S, Vainer B, Vogel U, Andersen J, et al. The association of polymorphisms in 5-fluorouracil metabolism genes with outcome in adjuvant treatment of colorectal cancer. Pharmacogenomics. 2011;12:1257-67 pubmed publisher
    ..Low-expression alleles in thymidylate synthase (TYMS) were associated with decreased DFS and overall survival (DFS:hazard ratio [HR] exploration 2.65 [1...
  30. Schiffer C, Clifton I, Davisson V, Santi D, Stroud R. Crystal structure of human thymidylate synthase: a structural mechanism for guiding substrates into the active site. Biochemistry. 1995;34:16279-87 pubmed
    The crystal structure of human thymidylate synthase, a target for anti-cancer drugs, is determined to 3.0 A resolution and refined to a crystallographic residual of 17.8%...
  31. Gusella M, Padrini R. G>C SNP of thymidylate synthase with respect to colorectal cancer. Pharmacogenomics. 2007;8:985-96 pubmed
    Several studies indicate that low thymidylate synthase (TS) protein levels in tumor and normal tissues of colorectal cancer patients are associated with better clinical response to fluorouracil-based chemotherapy and higher risk of ..
  32. James H, Gillis D, Hissaria P, Lester S, Somogyi A, Cleland L, et al. Common polymorphisms in the folate pathway predict efficacy of combination regimens containing methotrexate and sulfasalazine in early rheumatoid arthritis. J Rheumatol. 2008;35:562-71 pubmed
    ..Response to therapy was associated with SLC19A1, MTR, and TYMS polymorphisms...
  33. Kristensen M, Weidinger M, Bzorek M, Pedersen P, Mejer J. Correlation between thymidylate synthase gene variants, RNA and protein levels in primary colorectal adenocarcinomas. J Int Med Res. 2010;38:484-97 pubmed
    This study was designed to compare thymidylate synthase (TS) genotype, mRNA and protein levels in primary colorectal adenocarcinoma, and to examine the correlation between microsatellite instability (MSI) and TS expression...
  34. Shahrokni A, Rajebi M, Saif M. Toxicity and efficacy of 5-fluorouracil and capecitabine in a patient with TYMS gene polymorphism: A challenge or a dilemma?. Clin Colorectal Cancer. 2009;8:231-4 pubmed publisher
    ..The active metabolite, 5-fluorodeoxyuridine monophosphate inhibits thymidylate synthase (TS), thus preventing DNA synthesis, which leads to imbalanced cell growth and ultimately cell death...
  35. de Bock C, Garg M, Scott N, Sakoff J, Scorgie F, Ackland S, et al. Association of thymidylate synthase enhancer region polymorphisms with thymidylate synthase activity in vivo. Pharmacogenomics J. 2011;11:307-14 pubmed publisher
    Two known polymorphisms in the 5' enhancer region (ER) of the thymidylate synthase (TS) gene, a variable number of tandem repeats of a 28?bp sequence (2R/3R) and a further G>C single nucleotide substitution within the repeats, result ..
  36. Henríquez Hernández L, Murias Rosales A, Hernandez Gonzalez A, Cabrera de León A, Díaz Chico B, Mori De Santiago M, et al. Gene polymorphisms in TYMS, MTHFR, p53 and MDR1 as risk factors for breast cancer: a case-control study. Oncol Rep. 2009;22:1425-33 pubmed
    ..05). Gene polymorphisms vary by regions. The present study contributes to the characterization of the genetic pattern of the Canary population. ..
  37. Jakobsen A, Nielsen J, Gyldenkerne N, Lindeberg J. Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphism in normal tissue as predictors of fluorouracil sensitivity. J Clin Oncol. 2005;23:1365-9 pubmed
    To analyze thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with respect to fluorouracil (FU) sensitivity...
  38. Goekkurt E, Hoehn S, Wolschke C, Wittmer C, Stueber C, Hossfeld D, et al. Polymorphisms of glutathione S-transferases (GST) and thymidylate synthase (TS)--novel predictors for response and survival in gastric cancer patients. Br J Cancer. 2006;94:281-6 pubmed
    ..1;7.0) in patients with at least one GSTP1-105I allele (P=0.037). Patients possessing a favourable thymidylate synthase (TS) genotype (2R/2R, 2R/3RC, 3RC/3RC) experienced a superior survival time of 10.2 months (95% CI 5.1;15...
  39. Buqué A, Aresti U, Calvo B, Sh Muhialdin J, Munoz A, Carrera S, et al. Thymidylate synthase expression determines pemetrexed targets and resistance development in tumour cells. PLoS ONE. 2013;8:e63338 pubmed publisher
    ..These results may be useful to employ targets gene expression as resistance markers, a valuable tool for identifying patients likely to receive combination therapy to prevent the development of resistance. ..
  40. Brown K, Kluijtmans L, Young I, McNulty H, Mitchell L, Yarnell J, et al. The thymidylate synthase tandem repeat polymorphism is not associated with homocysteine concentrations in healthy young subjects. Hum Genet. 2004;114:182-5 pubmed
    b>Thymidylate synthase (TYMS) and 5,10-methylenetetrahydrofolate reductase (MTHFR) may compete for their common cofactor 5,10-methylenetetrahyhdrofolate (5,10-meTHF)...
  41. Martinez Balibrea E, Abad A, Aranda E, Sastre J, Manzano J, Diaz Rubio E, et al. Pharmacogenetic approach for capecitabine or 5-fluorouracil selection to be combined with oxaliplatin as first-line chemotherapy in advanced colorectal cancer. Eur J Cancer. 2008;44:1229-37 pubmed publisher
    ..006) were strong independent prognostic factors. According to this, patients harbouring TS-3'UTR +6bp/+6bp and ERCC1-118C/T or C/C genotypes may better receive capecitabine instead of 5FU in an oxaliplatin-based first-line treatment. ..
  42. Tanaka F, Wada H, Fukui Y, Fukushima M. Thymidylate synthase (TS) gene expression in primary lung cancer patients: a large-scale study in Japanese population. Ann Oncol. 2011;22:1791-7 pubmed publisher
    Previous small-sized studies showed lower thymidylate synthase (TS) expression in adenocarcinoma of the lung, which may explain higher antitumor activity of TS-inhibiting agents such as pemetrexed...
  43. Krajinovic M, Costea I, Primeau M, Dulucq S, Moghrabi A. Combining several polymorphisms of thymidylate synthase gene for pharmacogenetic analysis. Pharmacogenomics J. 2005;5:374-80 pubmed
    b>Thymidylate synthase (TS) is an essential enzyme in proliferating cells and an important target for several chemotherapeutics...
  44. Peters G, Backus H, Freemantle S, van Triest B, Codacci Pisanelli G, van der Wilt C, et al. Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism. Biochim Biophys Acta. 2002;1587:194-205 pubmed
    b>Thymidylate synthase (TS) is a key enzyme in the de novo synthesis of 2'-deoxythymidine-5'-monophosphate (dTMP) from 2'-deoxyuridine-5'-monophosphate (dUMP), for which 5,10-methylene-tetrahydrofolate (CH(2)-THF) is the methyl donor...
  45. Fernández Contreras M, Sánchez Hernández J, Gonzalez E, Herráez B, Dominguez I, Lozano M, et al. Combination of polymorphisms within 5' and 3' untranslated regions of thymidylate synthase gene modulates survival in 5 fluorouracil-treated colorectal cancer patients. Int J Oncol. 2009;34:219-29 pubmed
    ..1%) among patients with the unfavourable G&6+/6+ combination. In our study the combination of high TS expression genotypes G&6+/6+ identifies a group of high risk within CRC patients treated with 5FU. ..
  46. Boni V, Bitarte N, Cristobal I, Zarate R, Rodriguez J, Maiello E, et al. miR-192/miR-215 influence 5-fluorouracil resistance through cell cycle-mediated mechanisms complementary to its post-transcriptional thymidilate synthase regulation. Mol Cancer Ther. 2010;9:2265-75 pubmed publisher
    b>Thymidylate synthase (TYMS) is a target of the most widely used chemotherapeutic agents against gastrointestinal malignancies, the fluoropyrimidine-based therapy...
  47. Uchida K, Hayashi K, Kawakami K, Schneider S, Yochim J, Kuramochi H, et al. 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. Clin Cancer Res. 2004;10:433-9 pubmed
    b>Thymidylate synthase (TS), the target enzyme of the fluoropyrimidine class of drugs, has a 28-bp repeat polymorphism in the promoter region that has been associated with response of tumors to 5-fluorouracil-based therapy...
  48. Mauritz R, Giovannetti E, Beumer I, Smid K, van Groeningen C, Pinedo H, et al. Polymorphisms in the enhancer region of the thymidylate synthase gene are associated with thymidylate synthase levels in normal tissues but not in malignant tissues of patients with colorectal cancer. Clin Colorectal Cancer. 2009;8:146-54 pubmed publisher
    The enhancer region of the thymidylate synthase (TS) gene (TSER) contains a polymorphic tandem repeat sequence (2 or 3 repeats, 2R or 3R) and a single-nucleotide polymorphism (G > C) within the second repeat of the 3R alleles which ..
  49. Jekic B, Lukovic L, Bunjevacki V, Milic V, Novakovic I, Damnjanovic T, et al. Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients. Eur J Clin Pharmacol. 2013;69:377-83 pubmed publisher
    Gamma-glutamyl hydrolase (GGH), cyclin D1 (CCND1) and thymidylate synthase (TS) genes encode enzymes that are involved in methotrexate (MTX) action...
  50. Joshi M, Shirota Y, Danenberg K, Conlon D, Salonga D, Herndon J, et al. High gene expression of TS1, GSTP1, and ERCC1 are risk factors for survival in patients treated with trimodality therapy for esophageal cancer. Clin Cancer Res. 2005;11:2215-21 pubmed
    ..S-transferase pi (GSTP1) and excision cross-complementing gene 1 (ERCC1)] and 5-fluorouracil association [thymidylate synthase 1 (TS1)] were measured...
  51. Kim S, Park C, Park S, Park J, Lee J, Lee S. Genetic polymorphisms associated with 5-Fluorouracil-induced neurotoxicity. Chemotherapy. 2010;56:313-7 pubmed publisher
    ..from fluorouracil therapy is known to be associated with the individual genetic background of the enzymes, thymidylate synthase and dihydropyrimidine dehydrogenase...
  52. Wilding C, Relton C, Sutton M, Jonas P, Lynch S, Tawn E, et al. Thymidylate synthase repeat polymorphisms and risk of neural tube defects in a population from the northern United Kingdom. Birth Defects Res A Clin Mol Teratol. 2004;70:483-5 pubmed
    A 28-bp repeat polymorphism in the 5'UTR of the thymidylate synthase (TYMS) gene represents a candidate risk factor for neural tube defects (NTDs) due to involvement in folate-dependent homocysteine metabolism. Non-Hispanic, white, U.S...
  53. Lassmann S, Hennig M, Rosenberg R, Nahrig J, Schreglmann J, Krause F, et al. Thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase mRNA expression in primary colorectal tumors-correlation to tumor histopathology and clinical follow-up. Int J Colorectal Dis. 2006;21:238-47 pubmed
    Evaluation of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and thymidylate synthase (TS) mRNA levels in formalin-fixed, and paraffin-embedded tissues of patients with colorectal cancer and their prognostic and/or ..
  54. Kumar K, Vamsy M, Jamil K. Thymidylate synthase gene polymorphisms effecting 5-FU response in breast cancer patients. Cancer Biomark. 2010;6:83-93 pubmed publisher
    ..The target enzyme for 5- Fluorouracil is thymidylate synthase (TYMS) this enzyme is also involved in folate metabolism...
  55. Zucali P, Giovannetti E, Destro A, Mencoboni M, Ceresoli G, Gianoncelli L, et al. Thymidylate synthase and excision repair cross-complementing group-1 as predictors of responsiveness in mesothelioma patients treated with pemetrexed/carboplatin. Clin Cancer Res. 2011;17:2581-90 pubmed publisher
    ..retrospective study aimed to assess the role of excision repair cross-complementing group-1 (ERCC1) and thymidylate synthase (TS) in tumors, and correlate expression levels and polymorphisms of these key determinants of drug ..
  56. Hitre E, Budai B, Adleff V, Czeglédi F, Horvath Z, Gyergyay F, et al. Influence of thymidylate synthase gene polymorphisms on the survival of colorectal cancer patients receiving adjuvant 5-fluorouracil. Pharmacogenet Genomics. 2005;15:723-30 pubmed
    The present study aimed to prospectively investigate the influence of thymidylate synthase (TS) polymorphisms (5'-TSER, 3'-TSUTR) on the disease-free survival (DFS) and overall survival (OS) of patients with colorectal cancer (CRC) who ..
  57. Kim S, Ozawa S, Saito Y, Kurose K, Kaniwa N, Kamatani N, et al. Fourteen novel genetic variations and haplotype structures of the TYMS gene encoding human thymidylate synthase (TS). Drug Metab Pharmacokinet. 2006;21:509-16 pubmed
    Forty genetic variations including 14 novel ones were found in the human TYMS gene, which encodes thymidylate synthase, in 263 Japanese cancer patients who received 5-fluorouracil (FU)-based chemotherapy...
  58. Fujishima M, Inui H, Hashimoto Y, Azumi T, Yamamoto N, Kato H, et al. Relationship between thymidylate synthase (TYMS) gene polymorphism and TYMS protein levels in patients with high-risk breast cancer. Anticancer Res. 2010;30:4373-9 pubmed
    The thymidylate synthase gene (TYMS) has three functional polymorphisms which are associated with TYMS expression...
  59. Luo H, Lu X, Yao Y, Horie N, Takeishi K, Jorde L, et al. Length polymorphism of thymidylate synthase regulatory region in Chinese populations and evolution of the novel alleles. Biochem Genet. 2002;40:41-51 pubmed
    The tandemly repeated 28-bp sequence in the 5'-terminal regulatory region of human thymidylate synthase (TSER), which has been reported to be polymorphic in different populations, was surveyed in 668 Chinese from 9 Han groups, 8 ethnic ..
  60. Graziano F, Kawakami K, Watanabe G, Ruzzo A, Humar B, Santini D, et al. Association of thymidylate synthase polymorphisms with gastric cancer susceptibility. Int J Cancer. 2004;112:1010-4 pubmed
    We investigated in a case-control study a possible role of thymidylate synthase gene (TS) polymorphisms for gastric cancer susceptibility...
  61. Schwab M, Zanger U, Marx C, Schaeffeler E, Klein K, Dippon J, et al. Role of genetic and nongenetic factors for fluorouracil treatment-related severe toxicity: a prospective clinical trial by the German 5-FU Toxicity Study Group. J Clin Oncol. 2008;26:2131-8 pubmed publisher
    To assess the predictive value of polymorphisms in dihydropyrimidine dehydrogenase (DPYD ), thymidylate synthase (TYMS ), and methylene tetrahydrofolate reductase (MTHFR ) and of nongenetic factors for severe leukopenia, diarrhea, and ..
  62. Gusella M, Frigo A, Bolzonella C, Marinelli R, Barile C, Bononi A, et al. Predictors of survival and toxicity in patients on adjuvant therapy with 5-fluorouracil for colorectal cancer. Br J Cancer. 2009;100:1549-57 pubmed publisher
    ..5FU pharmacokinetics was evaluated at the first cycle. Thymidylate synthase (TYMS) 5'UTR and 3'UTR polymorphisms and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C ..
  63. Gibson L, Celeste L, Lovelace L, Lebioda L. Structures of human thymidylate synthase R163K with dUMP, FdUMP and glutathione show asymmetric ligand binding. Acta Crystallogr D Biol Crystallogr. 2011;67:60-6 pubmed publisher
    b>Thymidylate synthase (TS) is a well validated target in cancer chemotherapy...
  64. Lee S, Noh K, Lee J, Lee E, Min K, Hur G, et al. Thymidylate synthase and ERCC1 as predictive markers in patients with pulmonary adenocarcinoma treated with pemetrexed and cisplatin. Lung Cancer. 2013;81:102-8 pubmed publisher
    Increased expression of thymidylate synthase (TS) is thought to be associated with resistance to antifolate drugs such as pemetrexed...
  65. Marcuello E, Altes A, del Rio E, César A, Menoyo A, Baiget M. 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. Int J Cancer. 2004;112:733-7 pubmed
    b>Thymidylate synthase (TS) is the primary target of 5-fluorouracil (5-FU). A VNTR polymorphism in the TS promoter region is associated with the efficacy of 5-FU-based chemotherapy in colorectal cancer...
  66. Weekes C, Nallapareddy S, Rudek M, Norris Kirby A, Laheru D, Jimeno A, et al. Thymidylate synthase (TYMS) enhancer region genotype-directed phase II trial of oral capecitabine for 2nd line treatment of advanced pancreatic cancer. Invest New Drugs. 2011;29:1057-65 pubmed publisher
    ..toxicity associated with second-line capecitabine treatment of advanced pancreatic cancer patients harboring the TYMS *2/*2 allele...
  67. Mandola M, Stoehlmacher J, Muller Weeks S, Cesarone G, Yu M, Lenz H, et al. A novel single nucleotide polymorphism within the 5' tandem repeat polymorphism of the thymidylate synthase gene abolishes USF-1 binding and alters transcriptional activity. Cancer Res. 2003;63:2898-904 pubmed
    b>Thymidylate synthase (TS) gene expression is modulated by a polymorphism in the 5' regulatory region of the gene...
  68. Sharp L, Little J. Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am J Epidemiol. 2004;159:423-43 pubmed
    ..synthase reductase (MTRR A66G), cystathionine beta-synthase (CBS exon 8, 68-base-pair insertion), and thymidylate synthase (TS enhancer region and 3' untranslated region)--have been investigated in colorectal neoplasia...
  69. Gao C, Takezaki T, Wu J, Liu Y, Ding J, Li S, et al. Polymorphisms in thymidylate synthase and methylenetetrahydrofolate reductase genes and the susceptibility to esophageal and stomach cancer with smoking. Asian Pac J Cancer Prev. 2004;5:133-8 pubmed
  70. Grieu F, Powell B, Beilby J, Iacopetta B. Methylenetetrahydrofolate reductase and thymidylate synthase polymorphisms are not associated with breast cancer risk or phenotype. Anticancer Res. 2004;24:3215-9 pubmed
    ..Functional genetic variants in the methylene tetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) genes may be risk factors for breast cancer because of their central roles in cellular folate ..
  71. Oguri T, Achiwa H, Bessho Y, Muramatsu H, Maeda H, Niimi T, et al. The role of thymidylate synthase and dihydropyrimidine dehydrogenase in resistance to 5-fluorouracil in human lung cancer cells. Lung Cancer. 2005;49:345-51 pubmed
    The expressions of thymidylate synthase (TS) and intracellular metabolic enzymes have been reported to be associated with the sensitivity and/or resistance to 5-fluorouracil (5-FU)...
  72. Massacesi C, Terrazzino S, Marcucci F, Rocchi M, Lippe P, Bisonni R, et al. Uridine diphosphate glucuronosyl transferase 1A1 promoter polymorphism predicts the risk of gastrointestinal toxicity and fatigue induced by irinotecan-based chemotherapy. Cancer. 2006;106:1007-16 pubmed
    ..in uridine diphosphate glucuronosyl transferase (UGT1A1), methylenetetrahydrofolate reductase (MTHFR), and thymidylate synthase (TS) genes, and the incidence of the adverse effects of irinotecan and raltitrexed in previously heavily ..
  73. Dotor E, Cuatrecases M, Martínez Iniesta M, Navarro M, Vilardell F, Guino E, et al. Tumor thymidylate synthase 1494del6 genotype as a prognostic factor in colorectal cancer patients receiving fluorouracil-based adjuvant treatment. J Clin Oncol. 2006;24:1603-11 pubmed
    The purpose of this study was to analyze the value of germline and tumor thymidylate synthase (TS) genotyping as a prognostic marker in a series of colorectal cancer patients receiving adjuvant fluorouracil (FU) -based treatment...
  74. Campalani E, Arenas M, Marinaki A, Lewis C, Barker J, Smith C. Polymorphisms in folate, pyrimidine, and purine metabolism are associated with efficacy and toxicity of methotrexate in psoriasis. J Invest Dermatol. 2007;127:1860-7 pubmed
    ..The reduced folate carrier (RFC) 80A allele and the thymidylate synthase (TS) 3'-untranslated region (3'-UTR) 6 bp deletion were associated with methotrexate-induced toxicity (P=0...
  75. Gibson L, Lovelace L, Lebioda L. The R163K mutant of human thymidylate synthase is stabilized in an active conformation: structural asymmetry and reactivity of cysteine 195. Biochemistry. 2008;47:4636-43 pubmed publisher
    Loop 181-197 of human thymidylate synthase (hTS) populates two conformational states...
  76. Lima A, Azevedo R, Sousa H, Seabra V, Medeiros R. Current approaches for TYMS polymorphisms and their importance in molecular epidemiology and pharmacogenetics. Pharmacogenomics. 2013;14:1337-51 pubmed publisher
    ..However, several mechanisms of resistance to TS inhibitors have been explained as linked to TYMS overexpression...
  77. Ichikawa W, Uetake H, Shirota Y, Yamada H, Nishi N, Nihei Z, et al. Combination of dihydropyrimidine dehydrogenase and thymidylate synthase gene expressions in primary tumors as predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy for metastatic colorectal cancer. Clin Cancer Res. 2003;9:786-91 pubmed
    Dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) gene expressions in metastatic colorectal cancer have been reported to be predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy...
  78. Stoehlmacher J, Park D, Zhang W, Yang D, Groshen S, Zahedy S, et al. A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer. Br J Cancer. 2004;91:344-54 pubmed
    ..genes XPD, ERCC1, XRCC1, XPA, and metabolising genes glutathione S-transferase GSTP1, GSTT1, GSTM1, and thymidylate synthase (TS) were assessed retrospectively in 106 patients with refractory stage IV disease who received 5-FU/..
  79. Zhang J, Cui Y, Kuang G, Li Y, Wang N, Wang R, et al. Association of the thymidylate synthase polymorphisms with esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma. Carcinogenesis. 2004;25:2479-85 pubmed
    Polymorphisms in the untranslated regions (UTRs) of the thymidylate synthase (TS) gene, which may modulate TS transcription and expression, have been associated with susceptibility and prognosis of several tumors...
  80. Calascibetta A, Cabibi D, Martorana A, Sanguedolce G, Rausa L, Feo S, et al. Thymidylate synthase gene promoter polymorphisms are associated with TSmRNA expressions but not with microsatellite instability in colorectal cancer. Anticancer Res. 2004;24:3875-80 pubmed
    ..MSI status and the TSmRNA expression, the polymorphisms of 5-Fluorouracil (5-FU cellular target, the enzyme thymidylate synthase (TS) and TS expression evaluated by means of immunohistochemistry...
  81. Weisman M, Furst D, Park G, Kremer J, Smith K, Wallace D, et al. Risk genotypes in folate-dependent enzymes and their association with methotrexate-related side effects in rheumatoid arthritis. Arthritis Rheum. 2006;54:607-12 pubmed
    ..Low-penetrance risk genotypes in methylenetetrahydrofolate reductase (MTHFR) 677TT, thymidylate synthase (TSER) *2/*2 (variable number of tandem repeats), amino imidazole ribonucleotide transformylase (ATIC) ..
  82. Brody J, Hucl T, Gallmeier E, Winter J, Kern S, Murphy K. Genomic copy number changes affecting the thymidylate synthase (TYMS) gene in cancer: a model for patient classification to aid fluoropyrimidine therapy. Cancer Res. 2006;66:9369-73 pubmed
    b>Thymidylate synthase (TS) is an important target for 5-fluorouracil (5FU)-based therapy...
  83. Takatori R, Takahashi K, Tokunaga D, Hojo T, Fujioka M, Asano T, et al. ABCB1 C3435T polymorphism influences methotrexate sensitivity in rheumatoid arthritis patients. Clin Exp Rheumatol. 2006;24:546-54 pubmed
    ..ATIC) C347G and a 6bp-deletion polymorphism in the 3'-untranslated region of the thymidylase synthase (TYMS) gene are predictive of MTX sensitivity and its adverse effects...
  84. Martinez Balibrea E, Manzano J, Martinez Cardus A, Moran T, Cirauqui B, Catot S, et al. 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 plu. Oncol Rep. 2007;17:637-45 pubmed
    The aim of this study was to investigate the influence of combining thymidylate synthase (TS), X-ray cross complementing factor 1 (XRCC1) and uridine diphosphate glucoronosyltransferase (UGT1A1 *28) polymorphism genotypes in response rate ..
  85. Yu K, Wang W, Ding Y, Li H, Wang Z. Polymorphism of thymidylate synthase gene associated with its protein expression in human colon cancer. World J Gastroenterol. 2008;14:617-21 pubmed
    To correlate the polymorphisms in the 5'-untranslated region with thymidylate synthase (TS) protein expression in Han Chinese colonic neoplasms. Adenocarcinoma samples were from 68 patients who received no treatment before surgery...
  86. Wang Z, Hu Y, Zhao H, Fu C. [Thymidylate synthase expression and therapeutic effect analysis of pemetrexed in advanced lung adenocarcinoma]. Nan Fang Yi Ke Da Xue Xue Bao. 2010;30:978-80 pubmed
    To investigate the expression of thymidylate synthase (TS) in patients with advanced lung adenocarcinoma and its relation with the therapeutic effect of pemetrexed...
  87. Ghosh S, Winter J, Patel K, Kern S. Reexamining a proposal: thymidylate synthase 5'-untranslated region as a regulator of translation efficiency. Cancer Biol Ther. 2011;12:750-5 pubmed publisher
    The DNA replicative gene, thymidylate synthase (TYMS), is inhibited upon treatment with the anticancer drug 5-fluorouracil (5FU)...
  88. Nakagawa T, Tanaka F, Otake Y, Yanagihara K, Miyahara R, Matsuoka K, et al. Prognostic value of thymidylate synthase expression in patients with p-stage I adenocarcinoma of the lung. Lung Cancer. 2002;35:165-70 pubmed
    We investigated thymidylate synthase (TS) expression in tumor tissues and examined the relationship between TS expression and post-operative survival in patients with p-stage I adenocarcinoma of the lung...
  89. Hishida A, Matsuo K, Hamajima N, Ito H, Ogura M, Kagami Y, et al. Associations between polymorphisms in the thymidylate synthase and serine hydroxymethyltransferase genes and susceptibility to malignant lymphoma. Haematologica. 2003;88:159-66 pubmed
    Polymorphisms in thymidylate synthase (TS) 28-bp tandem repeats in the promoter region and in cytosolic serine hydroxymethyltransferase (SHMT1 C1420T) have been reported to modulate the risk of adult acute lymphocytic leukemia (ALL)...
  90. Zhang Z, Shi Q, Sturgis E, Spitz M, Hong W, Wei Q. Thymidylate synthase 5'- and 3'-untranslated region polymorphisms associated with risk and progression of squamous cell carcinoma of the head and neck. Clin Cancer Res. 2004;10:7903-10 pubmed
    ..We hypothesized that polymorphisms of the thymidylate synthase (TYMS) gene, which regulates a key enzyme in folate metabolism required for DNA synthesis and repair, are ..
  91. Chen J, Kyte C, Chan W, Wetmur J, Fuchs C, Giovannucci E. Polymorphism in the thymidylate synthase promoter enhancer region and risk of colorectal adenomas. Cancer Epidemiol Biomarkers Prev. 2004;13:2247-50 pubmed
    b>Thymidylate synthase (TS), a key one-carbon metabolizing gene, encodes an enzyme that converts dUMP to dTMP, the rate-limiting nucleotide in DNA synthesis...
  92. Wang L, Guo R, Fan Z, He X, Gao S, Guo H, et al. Association of methylenetetrahydrofolate reductase and thymidylate synthase promoter polymorphisms with genetic susceptibility to esophageal and cardia cancer in a Chinese high-risk population. Dis Esophagus. 2005;18:177-84 pubmed
    Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) are key enzymes in folate metabolism, which is essential for normal DNA methylation and synthesis...