thymidylate synthase

Summary

Summary: An enzyme of the transferase class that catalyzes the reaction 5,10-methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45.

Top Publications

  1. ncbi 5-fluorouracil: mechanisms of action and clinical strategies
    Daniel B Longley
    Cancer Research Centre, Department of Oncology, Queen s University Belfast, University Floor, Belfast City Hospital, 97 Lisburn Road, Belfast BT9 7AB, Northern Ireland
    Nat Rev Cancer 3:330-8. 2003
  2. pmc Thymidylate synthase as a determinant of pemetrexed sensitivity in non-small cell lung cancer
    K Takezawa
    Department of Medical Oncology, Kinki University Faculty of Medicine, 377 2 Ohno Higashi, Osaka Sayama, Osaka 589 8511, Japan
    Br J Cancer 104:1594-601. 2011
  3. ncbi ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy
    Y Shirota
    University of Southern California/Norris Comprehensive Cancer Center and Response Genetics Inc, Los Angeles, CA 90033, USA
    J Clin Oncol 19:4298-304. 2001
  4. ncbi Thymidylate synthase expression and prognosis in colorectal cancer: a systematic review and meta-analysis
    Sanjay Popat
    Section of Cancer Genetics, Institute of Cancer Research, Sutton SM2 5NG, UK
    J Clin Oncol 22:529-36. 2004
  5. ncbi Thymidylate synthase and dihydrofolate reductase expression in non-small cell lung carcinoma: the association with treatment efficacy of pemetrexed
    Chung Yu Chen
    Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, No 7, Chung Shan South Road, Taipei 100, Taiwan
    Lung Cancer 74:132-8. 2011
  6. ncbi Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFOX-4 chemotherapy
    Annamaria Ruzzo
    Institute of Biochemistry G Fornaini, University of Urbino, Urbino, Italy
    J Clin Oncol 25:1247-54. 2007
  7. ncbi Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors
    P G Johnston
    NCI Navy Medical Oncology Branch, National Institutes of Health, Bethesda, Maryland 20889 5105
    Cancer Res 55:1407-12. 1995
  8. ncbi Significance of thymidylate synthase and thyroid transcription factor 1 expression in patients with nonsquamous non-small cell lung cancer treated with pemetrexed-based chemotherapy
    Jong Mu Sun
    Division of Hematology Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
    J Thorac Oncol 6:1392-9. 2011
  9. ncbi Thymidylate synthase expression and genotype have no major impact on the clinical outcome of colorectal cancer patients treated with 5-fluorouracil
    Marina Vignoli
    Fondazione Farmacogenomica Fiorgen, Sesto Fiorentino, Italy Dipartimento di Fisiopatologia Clinica, Sezione di Genetica Medica, Universita di Firenze, Firenze, Italy
    Pharmacol Res 64:242-8. 2011
  10. ncbi Thymidylate synthase and ERCC1 as predictive markers in patients with pulmonary adenocarcinoma treated with pemetrexed and cisplatin
    Seung Hyeun Lee
    Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, 126 1, Anam Dong 5 Ga, Seongbuk gu, Seoul 136 705, Republic of Korea
    Lung Cancer 81:102-8. 2013

Detail Information

Publications369 found, 100 shown here

  1. ncbi 5-fluorouracil: mechanisms of action and clinical strategies
    Daniel B Longley
    Cancer Research Centre, Department of Oncology, Queen s University Belfast, University Floor, Belfast City Hospital, 97 Lisburn Road, Belfast BT9 7AB, Northern Ireland
    Nat Rev Cancer 3:330-8. 2003
    ..Such target genes might prove to be therapeutically valuable as new targets for chemotherapy, or as predictive biomarkers of response to 5-FU-based chemotherapy...
  2. pmc Thymidylate synthase as a determinant of pemetrexed sensitivity in non-small cell lung cancer
    K Takezawa
    Department of Medical Oncology, Kinki University Faculty of Medicine, 377 2 Ohno Higashi, Osaka Sayama, Osaka 589 8511, Japan
    Br J Cancer 104:1594-601. 2011
    Although a high level of thymidylate synthase (TS) expression in malignant tumours has been suggested to be related to a reduced sensitivity to the antifolate drug pemetrexed, no direct evidence for such an association has been ..
  3. ncbi ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy
    Y Shirota
    University of Southern California/Norris Comprehensive Cancer Center and Response Genetics Inc, Los Angeles, CA 90033, USA
    J Clin Oncol 19:4298-304. 2001
    PURPOSE: To test the hypotheses of whether the relative mRNA expression of the thymidylate synthase (TS) gene and the excision cross-complementing (ERCC1) gene are associated with response to and survival of fluorouracil (5-FU)/..
  4. ncbi Thymidylate synthase expression and prognosis in colorectal cancer: a systematic review and meta-analysis
    Sanjay Popat
    Section of Cancer Genetics, Institute of Cancer Research, Sutton SM2 5NG, UK
    J Clin Oncol 22:529-36. 2004
    A number of studies have investigated the relationship between thymidylate synthase (TS) expression and survival in colorectal cancer (CRC) patients...
  5. ncbi Thymidylate synthase and dihydrofolate reductase expression in non-small cell lung carcinoma: the association with treatment efficacy of pemetrexed
    Chung Yu Chen
    Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, No 7, Chung Shan South Road, Taipei 100, Taiwan
    Lung Cancer 74:132-8. 2011
    b>Thymidylate synthase (TS) and dihydrofolate reductase (DHFR) are target enzymes of inhibition by pemetrexed, an antifolate for treatment of advanced non-small-cell lung cancer (NSCLC)...
  6. ncbi Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFOX-4 chemotherapy
    Annamaria Ruzzo
    Institute of Biochemistry G Fornaini, University of Urbino, Urbino, Italy
    J Clin Oncol 25:1247-54. 2007
    ....
  7. ncbi Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors
    P G Johnston
    NCI Navy Medical Oncology Branch, National Institutes of Health, Bethesda, Maryland 20889 5105
    Cancer Res 55:1407-12. 1995
    b>Thymidylate synthase (TS) is the target enzyme for 5-fluorouracil (5-FU)...
  8. ncbi Significance of thymidylate synthase and thyroid transcription factor 1 expression in patients with nonsquamous non-small cell lung cancer treated with pemetrexed-based chemotherapy
    Jong Mu Sun
    Division of Hematology Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
    J Thorac Oncol 6:1392-9. 2011
    This study is to evaluate whether thymidylate synthase (TS) or thyroid transcription factor 1 (TTF1) protein expression can predict clinical outcomes for pemetrexed-based chemotherapy in patients with nonsquamous non-small cell lung ..
  9. ncbi Thymidylate synthase expression and genotype have no major impact on the clinical outcome of colorectal cancer patients treated with 5-fluorouracil
    Marina Vignoli
    Fondazione Farmacogenomica Fiorgen, Sesto Fiorentino, Italy Dipartimento di Fisiopatologia Clinica, Sezione di Genetica Medica, Universita di Firenze, Firenze, Italy
    Pharmacol Res 64:242-8. 2011
    b>Thymidylate synthase (TS) expression levels appear to be related to response to 5-fluorouracil-(5-FU)-based chemotherapy in colorectal cancer (CRC) patients...
  10. ncbi Thymidylate synthase and ERCC1 as predictive markers in patients with pulmonary adenocarcinoma treated with pemetrexed and cisplatin
    Seung Hyeun Lee
    Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, 126 1, Anam Dong 5 Ga, Seongbuk gu, Seoul 136 705, Republic of Korea
    Lung Cancer 81:102-8. 2013
    Increased expression of thymidylate synthase (TS) is thought to be associated with resistance to antifolate drugs such as pemetrexed...
  11. ncbi Synergistic antitumor effect of S-1 and the epidermal growth factor receptor inhibitor gefitinib in non-small cell lung cancer cell lines: role of gefitinib-induced down-regulation of thymidylate synthase
    Takafumi Okabe
    Department of Medical Oncology, Kinki University School of Medicine, Osaka Sayama, Osaka, Japan
    Mol Cancer Ther 7:599-606. 2008
    ..Gefitinib inhibited the expression of the transcription factor E2F-1, resulting in the down-regulation of thymidylate synthase at the mRNA and protein levels...
  12. ncbi A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels
    Michael V Mandola
    Department of Molecular Biology, The University of Medicine and Dentistry of New Jersey, School of Osteopathic Medicine, Stratford, New Jersey 08084, USA
    Pharmacogenetics 14:319-27. 2004
    A 6 bp deletion polymorphism in the thymidylate synthase (TS) gene was investigated in order to determine its function.
  13. ncbi Identification and functional analysis of single nucleotide polymorphism in the tandem repeat sequence of thymidylate synthase gene
    Kazuyuki Kawakami
    Department of Surgery, Kanazawa University School of Medicine, Kanazawa 920 8641, Japan
    Cancer Res 63:6004-7. 2003
    The variable number of tandem repeat (VNTR) of thymidylate synthase (TS) gene, mainly 2 repeat (2R) and 3 repeat (3R), is one of the genetic variations that can potentially predict the effectiveness of 5-fluorouracil-based chemotherapy...
  14. ncbi 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
    Thierry Dervieux
    Prometheus Laboratories, San Diego, California, USA
    Arthritis Rheum 50:2766-74. 2004
    ..MTXPGs) and inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC) and thymidylate synthase (TS)...
  15. ncbi miR-192/miR-215 influence 5-fluorouracil resistance through cell cycle-mediated mechanisms complementary to its post-transcriptional thymidilate synthase regulation
    Valentina Boni
    Oncology Unit, Casa Sollievo Sofferenza, S Giovanni Rotondo, Italy
    Mol Cancer Ther 9:2265-75. 2010
    b>Thymidylate synthase (TYMS) is a target of the most widely used chemotherapeutic agents against gastrointestinal malignancies, the fluoropyrimidine-based therapy...
  16. ncbi Thymidylate synthase but not excision repair cross-complementation group 1 tumor expression predicts outcome in patients with malignant pleural mesothelioma treated with pemetrexed-based chemotherapy
    Luisella Righi
    University of Torino, Division of Pathology, Thoracic Oncology, and Thoracic Surgery, Department of Clinical and Biological Sciences at San Luigi Hospital, Orbassano, Italy
    J Clin Oncol 28:1534-9. 2010
    The relationship between thymidylate synthase (TS) expression and outcome in patients with malignant pleural mesothelioma (MPM) treated with pemetrexed (P) was retrospectively evaluated.
  17. ncbi Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer
    H C Kwon
    Department of Internal Medicine, Dong A University College of Medicine, Busan, Korea
    Ann Oncol 18:504-9. 2007
    ..aim of this study was to determine whether expressions of the excision repair cross-complementing (ERCC1), thymidylate synthase (TS), and glutathione S-transferase P1 (GSTP1) predict clinical outcome in patients with advanced gastric ..
  18. ncbi The catalytic mechanism and structure of thymidylate synthase
    C W Carreras
    Department of Pharmaceutical Chemistry, University of California San Francisco 94143 0448, USA
    Annu Rev Biochem 64:721-62. 1995
    b>Thymidylate synthase (TS, EC 2.1.1.45) catalyzes the reductive methylation of dUMP by CH2H4folate to produce dTMP and H2folate. Knowledge of the catalytic mechanism and structure of TS has increased substantially over recent years...
  19. ncbi Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism
    G J Peters
    Department of Medical Oncology, VU University Medical Center, P O Box 7057, 1007 MB, Amsterdam, The Netherlands
    Biochim Biophys Acta 1587:194-205. 2002
    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...
  20. ncbi Role of genetic and nongenetic factors for fluorouracil treatment-related severe toxicity: a prospective clinical trial by the German 5-FU Toxicity Study Group
    Matthias Schwab
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, University of Stuttgart, Stuttgart, Germany
    J Clin Oncol 26:2131-8. 2008
    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 ..
  21. pmc Cloning, expression, and characterization of Babesia gibsoni dihydrofolate reductase-thymidylate synthase: inhibitory effect of antifolates on its catalytic activity and parasite proliferation
    Gabriel O Aboge
    National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada cho, Obihiro, Hokkaido, Japan
    Antimicrob Agents Chemother 52:4072-80. 2008
    Dihydrofolate reductase-thymidylate synthase (DHFR-TS) is a well-validated antifolate drug target in certain pathogenic apicomplexans, but not in the genus Babesia, including Babesia gibsoni...
  22. ncbi Predictive value of thymidylate synthase expression in advanced colorectal cancer patients receiving fluoropyrimidine-based chemotherapy: evidence from 24 studies
    Li Xin Qiu
    Cancer Center, Nanjing Drum Tower Hospital, Nanjing Medical University, Nanjing, China
    Int J Cancer 123:2384-9. 2008
    The published data about thymidylate synthase (TS) expression and its predictive value in advanced colorectal cancer (CRC) patients receiving fluoropyrimidine-based chemotherapy seemed inconclusive...
  23. ncbi Mechanisms of acquired chemoresistance to 5-fluorouracil and tomudex: thymidylate synthase dependent and independent networks
    Weiguang Wang
    Research Institute in Healthcare Science, School of Applied Sciences, University of Wolverhampton, Wolverhampton, WV1 1SB, UK
    Cancer Chemother Pharmacol 59:839-45. 2007
    b>Thymidylate synthase (TS) over-expression is widely accepted as a major molecular mechanism responsible for 5-fluorouracil (5-FU) and tomudex (TDX) resistance. In this study, the importance of TS in 5-FU and TDX resistance was evaluated.
  24. ncbi Immunohistochemical demonstration of fluoropyrimidine-metabolizing enzymes in various types of cancer
    Shingo Kamoshida
    Department of Pathology, Fujita Health University School of Medicine, Toyoake, Aichi 470 1192, Japan
    Oncol Rep 14:1223-30. 2005
    ..dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS)...
  25. ncbi Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphism in normal tissue as predictors of fluorouracil sensitivity
    Anders Jakobsen
    Danish Colorectal Cancer, Group South, Vejle Hospital, 7100 Vejle, Denmark
    J Clin Oncol 23:1365-9. 2005
    To analyze thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with respect to fluorouracil (FU) sensitivity.
  26. ncbi Case-control analysis of thymidylate synthase polymorphisms and risk of lung cancer
    Qiuling Shi
    Department of Epidemiology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Carcinogenesis 26:649-56. 2005
    ..b>Thymidylate synthase (TYMS) is involved in the metabolism of folate and the provision of nucleotides needed for DNA synthesis ..
  27. ncbi Thymidylate synthase gene polymorphism predicts toxicity in colorectal cancer patients receiving 5-fluorouracil-based chemotherapy
    Thierry Lecomte
    Service de Gastroenterologie, Assistance Publique Hopitaux de Paris, Hopital Europeen Georges Pompidou, Paris
    Clin Cancer Res 10:5880-8. 2004
    The target enzyme for 5-fluorouracil (5-FU) is thymidylate synthase (TS)...
  28. ncbi Human thymidylate synthase is in the closed conformation when complexed with dUMP and raltitrexed, an antifolate drug
    J Phan
    Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 92908, USA
    Biochemistry 40:1897-902. 2001
    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...
  29. ncbi Prognostic value of thymidylate synthase expression in patients with p-stage I adenocarcinoma of the lung
    Tatsuo Nakagawa
    Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, 53 Shogoin Kawahara cho, Sakyo ku, Kyoto 606 8397, Japan
    Lung Cancer 35:165-70. 2002
    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...
  30. ncbi 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
    Marianne C Nicolson
    Thoracic Oncology, Aberdeen Royal Infirmary, University of Aberdeen, Aberdeen, United Kingdom
    J Thorac Oncol 8:930-9. 2013
    ..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...
  31. ncbi Prognostic and predictive value of thymidylate synthase expression in primary colorectal cancer
    M Karlberg
    Department of Oncology and Pathology, CCK R8 03, Karolinska University Hospital, S 171 76 Stockholm, Sweden
    Anticancer Res 30:645-51. 2010
    To investigate thymidylate synthase (TS) expression in primary colorectal cancer (CRC) as a prognostic and predictive marker of benefit for adjuvant chemotherapy.
  32. ncbi Combined therapy with a thymidylate synthase-inhibiting vector and S-1 has effective antitumor activity against 5-FU-resistant tumors
    Kyuichi Kadota
    Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Kagawa University, Kagawa 761 0793, Japan
    Int J Oncol 38:355-63. 2011
    High levels of intratumoral thymidylate synthase (TS) expression are associated with resistance to 5-fluorourcil (5-FU)...
  33. ncbi The efficacy of pemetrexed as a third- or fourth-line therapy and the significance of thymidylate synthase expression in patients with advanced non-small cell lung cancer
    Myung Hee Chang
    Division of Hematology Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon dong, Seoul 135 710, Republic of Korea
    Lung Cancer 69:323-9. 2010
    ..We also analyzed thymidylate synthase (TS) expression in tumor tissues to determine whether TS expression is correlated with the clinical ..
  34. pmc Predictors of survival and toxicity in patients on adjuvant therapy with 5-fluorouracil for colorectal cancer
    M Gusella
    Laboratory of Pharmacology and Molecular Biology, Oncology Department, Azienda ULSS 18 Rovigo, Trecenta, Italy
    Br J Cancer 100:1549-57. 2009
    ..5FU pharmacokinetics was evaluated at the first cycle. Thymidylate synthase (TYMS) 5'UTR and 3'UTR polymorphisms and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C ..
  35. pmc Significance of folate receptor alpha and thymidylate synthase protein expression in patients with non-small-cell lung cancer treated with pemetrexed
    Daniel C Christoph
    Department of Medicine, Division of Medical Oncology, University of Colorado Denver, Aurora, Colorado 80045, USA
    J Thorac Oncol 8:19-30. 2013
    ..We investigated FRA as a biomarker for pemetrexed-based chemotherapy and compared it with thymidylate synthase (TS), the main target of pemetrexed.
  36. pmc Nuclear localization of de novo thymidylate biosynthesis pathway is required to prevent uracil accumulation in DNA
    Amanda J MacFarlane
    Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA
    J Biol Chem 286:44015-22. 2011
    ..de novo thymidylate biosynthesis, a pathway composed of the enzymes serine hydroxymethyltransferase (SHMT), thymidylate synthase (TYMS), and dihydrofolate reductase...
  37. ncbi Gene polymorphisms in TYMS, MTHFR, p53 and MDR1 as risk factors for breast cancer: a case-control study
    L A Henríquez-Hernández
    Clinical Science Department, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain
    Oncol Rep 22:1425-33. 2009
    ..05). Gene polymorphisms vary by regions. The present study contributes to the characterization of the genetic pattern of the Canary population...
  38. ncbi Altered tissue 3'-deoxy-3'-[18F]fluorothymidine pharmacokinetics in human breast cancer following capecitabine treatment detected by positron emission tomography
    Laura M Kenny
    Department of Oncology, Imperial College London, London, United Kingdom
    Clin Cancer Res 15:6649-57. 2009
    We showed in preclinical models that thymidylate synthase (TS) inhibition leads to redistribution of the nucleoside transporter, ENT1, to the cell membrane and hence increases tissue uptake of [(18)F]fluorothymidine (FLT)...
  39. pmc Pemetrexed indirectly activates the metabolic kinase AMPK in human carcinomas
    Scott B Rothbart
    Department of Pharmacology and Toxicology and the Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA
    Cancer Res 70:10299-309. 2010
    The chemotherapeutic drug pemetrexed, an inhibitor of thymidylate synthase, has an important secondary target in human leukemic cells, aminoimidazolecarboxamide ribonucleotide formyltransferase (AICART), the second folate-dependent enzyme ..
  40. pmc Molecular genetics of para-aminosalicylic acid resistance in clinical isolates and spontaneous mutants of Mycobacterium tuberculosis
    Vanessa Mathys
    Laboratory of Molecular Pathology of Tuberculosis, Pasteur Institute, Scientific Institute of Public Health, Brussels, Belgium
    Antimicrob Agents Chemother 53:2100-9. 2009
    ..The alternative mechanism(s) or pathway(s) associated with PAS resistance appears to be PAS concentration dependent, in marked contrast to thyA-mutated PAS-resistant isolates...
  41. ncbi Squamous cell carcinoma of the lung compared with other histotypes shows higher messenger RNA and protein levels for thymidylate synthase
    Paolo Ceppi
    Thoracic Oncology Unit, Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Orbassano, Torino, Italy
    Cancer 107:1589-96. 2006
    In patients with cancer, one of the main mechanism of resistance to antimetabolite drugs is related to higher levels of thymidylate synthase (TS) activity.
  42. ncbi Molecular mechanisms underlying the synergistic interaction of erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, with the multitargeted antifolate pemetrexed in non-small-cell lung cancer cells
    Elisa Giovannetti
    Division of Pharmacology and Chemotherapy, Department of Internal Medicine, 55, Via Roma, 56126 Pisa, Italy
    Mol Pharmacol 73:1290-300. 2008
    ..Cells were characterized by heterogeneous expression of pemetrexed determinants, including thymidylate synthase (TS) and dihydrofolate reductase (DHFR), and mutations potentially affecting chemosensitivity...
  43. ncbi The role of thymidylate synthase expression in prognosis and outcome of adjuvant chemotherapy in patients with rectal cancer
    P G Johnston
    National Cancer Institute Navy Medical Oncology Branch, National Cancer Institute, Bethesda, MD 20889
    J Clin Oncol 12:2640-7. 1994
    We assessed the prognostic importance of the level of thymidylate synthase (TS) expression in patients with primary rectal cancer and whether, for Dukes' B and C cancer patients, the benefit of chemotherapy was associated with TS ..
  44. ncbi P21Cip1 is a critical mediator of the cytotoxic action of thymidylate synthase inhibitors in colorectal carcinoma cells
    James I Geller
    Division of Molecular Therapeutics, Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cancer Res 64:6296-303. 2004
    ..colon carcinoma cell lines to the cytotoxic effects of 5-fluorouracil combined with leucovorin and to the thymidylate synthase inhibitor, ZD9331, dependent on thymineless stress-induced DNA damage, independent of p53...
  45. ncbi One-carbon metabolism related gene polymorphisms interact with alcohol drinking to influence the risk of colorectal cancer in Japan
    Keitaro Matsuo
    Division of Epidemiology and Prevention, Aichi Cancer Center, Nagoya 464 8681, Japan
    Carcinogenesis 26:2164-71. 2005
    ..genes for methylenetetrahydrofolate reductase), MTR A2756G (gene for methionine synthase) and TS (gene for thymidylate synthase) tandem repeats polymorphisms, have attracted attention...
  46. ncbi Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors
    A R Hanauske
    Eli Lilly and Company, Indianapolis, Indiana 46285, USA
    Oncologist 6:363-73. 2001
    ..inhibits multiple folate-dependent enzymes involved in both purine and pyrimidine synthesis including thymidylate synthase, dihydrofolate reductase, glycinamide ribonucleotide formyltransferase, and aminoimidazole carboxamide ..
  47. pmc Uracil incorporation into genomic DNA does not predict toxicity caused by chemotherapeutic inhibition of thymidylate synthase
    Yuhong Luo
    Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA
    DNA Repair (Amst) 7:162-9. 2008
    b>Thymidylate synthase (TS) is an important target of several chemotherapeutic agents, including 5-FU and raltitrexed (Tomudex). During TS inhibition, TTP levels decrease with a subsequent increase in dUTP...
  48. ncbi LY231514, a pyrrolo[2,3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes
    C Shih
    Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA
    Cancer Res 57:1116-23. 1997
    ..that LY231514 and its synthetic gamma-polyglutamates (glu3 and glu5) exert potent inhibition against thymidylate synthase (TS)...
  49. pmc A ribosomal function is necessary for efficient splicing of the T4 phage thymidylate synthase intron in vivo
    K Semrad
    Institute of Microbiology and Genetics, Vienna Biocenter, 1030 Wien, Austria
    Genes Dev 12:1327-37. 1998
    Splicing of the group I intron of the T4 thymidylate synthase (td) gene was uncoupled from translation by introducing stop codons in the upstream exon. This resulted in severe splicing deficiency in vivo...
  50. ncbi High gene expression of TS1, GSTP1, and ERCC1 are risk factors for survival in patients treated with trimodality therapy for esophageal cancer
    Mary Beth Moore Joshi
    Thoracic Oncology Program and Division of Cancer Biostatistics, Duke University Medical Center, Durham, NC 27710, USA
    Clin Cancer Res 11:2215-21. 2005
    ..To assess the relationship between molecular markers associated with chemotherapy resistance and survival in esophageal cancer patients treated with trimodality therapy...
  51. ncbi Thymidylate synthase gene variations: predictive and prognostic markers
    Georg Lurje
    Division of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, California, USA
    Mol Cancer Ther 8:1000-7. 2009
    ..Although conflicting results have been reported, higher thymidylate synthase (TS) protein and mRNA expression levels in tumors have generally been associated with poor clinical outcome ..
  52. ncbi E2F1 overexpression correlates with thymidylate synthase and survivin gene expressions and tumor proliferation in non small-cell lung cancer
    Cheng Long Huang
    Department of Second Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
    Clin Cancer Res 13:6938-46. 2007
    We investigated the clinical significance of E2F1 gene expression in relation to its target genes, thymidylate synthase (TS) and Survivin, in case of non-small-cell lung cancer (NSCLC).
  53. ncbi Methylenetetrahydrofolate reductase gene polymorphisms: genomic predictors of clinical response to fluoropyrimidine-based chemotherapy?
    E Marcuello
    Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Avda S Antoni M Claret 167, 08025, Barcelona, Spain
    Cancer Chemother Pharmacol 57:835-40. 2006
    ..Methylenetetrahydrofolate reductase (MTHFR) may play a central role in the action of 5-FU, an inhibitor of thymidylate synthase, by converting 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate...
  54. ncbi Uridine diphosphate glucuronosyl transferase 1A1 promoter polymorphism predicts the risk of gastrointestinal toxicity and fatigue induced by irinotecan-based chemotherapy
    Cristian Massacesi
    Department of Oncology and Radiotherapy, Ospedali Riuniti, Ancona, Italy
    Cancer 106:1007-16. 2006
    ..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 ..
  55. ncbi Pemetrexed (ALIMTA), a novel multitargeted antineoplastic agent
    Alex A Adjei
    Mayo Clinic and Foundation, Departments of Oncology, Rochester, Minnesota, USA
    Clin Cancer Res 10:4276s-4280s. 2004
    ..These enzymes are thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase...
  56. ncbi Up-regulation of extracellular signal-regulated kinase 1/2-dependent thymidylate synthase and thymidine phosphorylase contributes to cisplatin resistance in human non-small-cell lung cancer cells
    Jen Chung Ko
    Department of Internal Medicine, Hsinchu Hospital, Chiayi, Taiwan
    J Pharmacol Exp Ther 338:184-94. 2011
    ..to antimetabolite chemotherapeutics, and its mechanism of cytotoxicity is involved in the inhibition of thymidylate synthase (TS). TS and thymidine phosphorylase (TP) are key enzymes of the pyrimidine salvage pathway...
  57. pmc Nuclear thymidylate synthase expression, p53 expression and 5FU response in colorectal carcinoma
    N A Wong
    Department of Pathology, University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG
    Br J Cancer 85:1937-43. 2001
    b>Thymidylate synthase (TS) is a key enzyme in DNA synthesis and is inhibited by metabolites of the chemotherapeutic agent 5-fluorouracil (5FU)...
  58. pmc Antisense-induced down-regulation of thymidylate synthase and enhanced cytotoxicity of 5-FUdR in 5-FUdR-resistant HeLa cells
    P J Ferguson
    Cancer Research Laboratories, London Regional Cancer Centre, London, Ontario, Canada
    Br J Pharmacol 134:1437-46. 2001
    1. Thymidylate synthase (TS) is a target for several anticancer drugs...
  59. ncbi Inhibition of dUTPase induces synthetic lethality with thymidylate synthase-targeted therapies in non-small cell lung cancer
    Peter M Wilson
    Department of Pathology, Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, University of Southern California, Los Angeles, CA 90089, USA
    Mol Cancer Ther 11:616-28. 2012
    Chemotherapies that target thymidylate synthase (TS) continue to see considerable clinical expansion in non-small cell lung cancer (NSCLC). One drawback to TS-targeted therapies is drug resistance and subsequent treatment failure...
  60. ncbi New prognostic indicator for non-small-cell lung cancer, quantitation of thymidylate synthase by real-time reverse transcription polymerase chain reaction
    Yasushi Shintani
    Department of Surgery, E1, Osaka University Graduate School of Medicine, Osaka, Japan
    Int J Cancer 104:790-5. 2003
    b>Thymidylate synthase (TS) is an enzyme that catalyzes an important DNA biosynthesis process. The gene expression of TS has not been reported in non-small-cell lung cancer (NSCLC) patients...
  61. ncbi Discovery of a novel class of potent human deoxyuridine triphosphatase inhibitors remarkably enhancing the antitumor activity of thymidylate synthase inhibitors
    Seiji Miyahara
    Tsukuba Research Center, Taiho Pharmaceutical Co Ltd, Okubo 3, Tsukuba, Ibaraki 300 2611, Japan
    J Med Chem 55:2970-80. 2012
    ..This is the first in vivo evidence that human dUTPase inhibitors enhance the antitumor activity of TS inhibitors. On the basis of these findings, it was concluded that compound 26 is a promising candidate for clinical development...
  62. ncbi Pemetrexed for previously treated patients with non-small cell lung cancer and differences in efficacy according to thymidylate synthase expression
    Satoshi Igawa
    Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara, Japan
    Chemotherapy 58:313-20. 2012
    ..with advanced non-small cell lung cancer (NSCLC) including salvage treatment, and to evaluate whether thymidylate synthase (TS) expression is a predictor for pemetrexed efficacy...
  63. ncbi Associations between gene polymorphisms of thymidylate synthase with its protein expression and chemosensitivity to 5-fluorouracil in pancreatic carcinoma cells
    Qiang Zhang
    Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
    Chin Med J (Engl) 124:262-7. 2011
    b>Thymidylate synthase (TS) is a key regulatory enzyme for de novo DNA synthesis...
  64. pmc In vivo mutations of thymidylate synthase (encoded by thyA) are responsible for thymidine dependency in clinical small-colony variants of Staphylococcus aureus
    Indranil Chatterjee
    Institute of Medical Microbiology and Hygiene, Institutes of Infectious Disease Medicine, University of Saarland, Homburg Saar, Germany
    J Bacteriol 190:834-42. 2008
    ..As SXT inhibits the synthesis of tetrahydrofolic acid, which acts as a cofactor for thymidylate synthase (thyA), the survival of TD-SCVs depends exclusively on the availability of external thymidine...
  65. ncbi Polymorphisms in the thymidylate synthase and dihydropyrimidine dehydrogenase genes predict response and toxicity to capecitabine-raltitrexed in colorectal cancer
    Josefa Salgado
    Laboratory of Biotechnology, University Clinic of Navarra, 31008 Pamplona, Navarra, Spain
    Oncol Rep 17:325-8. 2007
    ..b>Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) gene polymorphisms could be highly informative tools in the ..
  66. pmc A multifactorial approach including tumoural epidermal growth factor receptor, p53, thymidylate synthase and dihydropyrimidine dehydrogenase to predict treatment outcome in head and neck cancer patients receiving 5-fluorouracil
    M C Etienne
    Centre Antoine Lacassagne, Nice, France
    Br J Cancer 79:1864-9. 1999
    The prognostic value of tumoural epidermal growth factor receptor (EGFR), p53, thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) was analysed on 82 advanced head and neck cancer patients (71 men, 11 women; mean age 59)...
  67. ncbi Comprehensive analysis of excision repair complementation group 1, glutathione S-transferase, thymidylate synthase and uridine diphosphate glucuronosyl transferase 1A1 polymorphisms predictive for treatment outcome in patients with advanced gastric cancer
    Bong Gun Seo
    Department of Internal Medicine, Dong A University College of Medicine, Busan, Korea
    Oncol Rep 22:127-36. 2009
    ..The low expression type (2R/2R, 2R/3C and 3C/3C) of TS was associated with a high incidence of grade >or=3 neutropenia in cases of advanced gastric cancer treated with FOLFIRI...
  68. ncbi Expression of thymidylate synthase in human non-small cell lung cancer
    Y Otake
    Department of Thoracic Surgery, Kyoto University Hospital
    Jpn J Cancer Res 90:1248-53. 1999
    5-Fluorouracil (5-FU) has been used worldwide, and the correlation between its effects and thymidylate synthase (TS) expression has been reported in gastrointestinal malignancy...
  69. ncbi Combining several polymorphisms of thymidylate synthase gene for pharmacogenetic analysis
    M Krajinovic
    Centre de Recherche, Hopital Sainte Justine, Centre Hospitalier Universitaire Mère Enfant, 3175 Cote Sainte Catherine, Montreal, Quebec, Canada H3T 1C5
    Pharmacogenomics J 5:374-80. 2005
    b>Thymidylate synthase (TS) is an essential enzyme in proliferating cells and an important target for several chemotherapeutics...
  70. ncbi Thymidilate synthase expression predicts longer survival in patients with stage II colon cancer treated with 5-flurouracil independently of microsatellite instability
    Marisa Donada
    ACADEM Department, Cattinara Hospital, University of Trieste, Surgical Pathology Bldg, Strada di Fiume 447, 34149 Trieste, Italy
    J Cancer Res Clin Oncol 137:201-10. 2011
    ..evaluated in patients with colon cancer, either the role of genes involved in the 5-FU pathway, such as thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) or the role of microsatellite ..
  71. ncbi Preoperative chemoradiation for rectal cancer using capecitabine and celecoxib correlated with posttreatment assessment of thymidylate synthase and thymidine phosphorylase expression
    Keith R Unger
    Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia 22908, USA
    Int J Radiat Oncol Biol Phys 80:1377-82. 2011
    b>Thymidylate synthase (TS) and thymidine phosphorylase (TP) expression have been shown to be predictors of response to therapy...
  72. pmc Structure of an RNA dimer of a regulatory element from human thymidylate synthase mRNA
    Sergey Dibrov
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Acta Crystallogr D Biol Crystallogr 67:97-104. 2011
    A sequence around the start codon of the mRNA of human thymidylate synthase (TS) folds into a secondary-structure motif in which the initiation site is sequestered in a metastable hairpin...
  73. pmc Kinetics and ligand-binding preferences of Mycobacterium tuberculosis thymidylate synthases, ThyA and ThyX
    Joshua H Hunter
    Department of Chemistry, University of Washington, Seattle, Washington, United States of America
    PLoS ONE 3:e2237. 2008
    ..b>Thymidylate synthase (TS) enzymes from other species offer good targets for drug development and the M...
  74. ncbi RAD001 shows activity against gastric cancer cells and overcomes 5-FU resistance by downregulating thymidylate synthase
    Kyung Hun Lee
    Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
    Cancer Lett 299:22-8. 2010
    ..Furthermore, RAD001 conferred sensitivity to 5-FU-resistant cell lines by downregulating thymidylate synthase (TS)...
  75. pmc Reexamining a proposal: thymidylate synthase 5'-untranslated region as a regulator of translation efficiency
    Soma Ghosh
    Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA
    Cancer Biol Ther 12:750-5. 2011
    The DNA replicative gene, thymidylate synthase (TYMS), is inhibited upon treatment with the anticancer drug 5-fluorouracil (5FU)...
  76. pmc Cooperation between an intrinsically disordered region and a helical segment is required for ubiquitin-independent degradation by the proteasome
    Sandra P Melo
    Department of Biological Sciences and Center for Colon Cancer Research, University of South Carolina, Columbia, South Carolina 29208, USA
    J Biol Chem 286:36559-67. 2011
    ..One such substrate is the pyrimidine biosynthetic enzyme thymidylate synthase (EC 2.1.1...
  77. ncbi Alternative thymidylate synthase, ThyX, involved in Corynebacterium glutamicum ATCC 13032 survival during stationary growth phase
    Mijeong Park
    Department of Biology, Kyung Hee University, Seoul, Korea
    FEMS Microbiol Lett 307:128-34. 2010
    A BLASTP search has shown the presence of a gene homologous to an alternative thymidylate synthase (TS), thyX, in Corynebacterium glutamicum ATCC 13032...
  78. pmc Prognostic significance of miR-215 in colon cancer
    Mihriban Karaayvaz
    Department of Pathology, State University of New York at Stony Brook, Stony Brook, NY 11794 8691, USA
    Clin Colorectal Cancer 10:340-7. 2011
    We have previously shown that miR-215 suppressed the expression of key targets such as thymidylate synthase (TS), dihydrofolate reductase, and denticleless protein homolog (DTL) in colon cancer...
  79. ncbi Expression of thymidylate synthase is correlated with proliferative activity in non-small cell lung cancer (NSCLC)
    Tatsuo Nakagawa
    Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, 53 Shogoin Kawahara cho, Sakyo ku, Kyoto 606 8507, Japan
    Lung Cancer 43:145-9. 2004
    Many experimental studies have revealed that enhanced thymidylate synthase (TS) expression is significantly correlated with higher proliferative activity of tumor cells, which may account for a poor prognosis of high-TS patients...
  80. ncbi 2-[11C]thymidine positron emission tomography as an indicator of thymidylate synthase inhibition in patients treated with AG337
    Paula Wells
    Imperial College School of Medicine, Hammersmith Hospital, London, UK
    J Natl Cancer Inst 95:675-82. 2003
    Some anticancer drugs inhibit thymidylate synthase (TS), a key enzyme for thymidine nucleotide biosynthesis. Cells can compensate for depleted thymidine levels by taking up extracellular thymidine via a salvage pathway...
  81. pmc Flavin-dependent thymidylate synthase ThyX activity: implications for the folate cycle in bacteria
    Damien Leduc
    Inserm Avenir Group, Institut de Génétique et de Microbiologie, CNRS UMR8621, F 91405 Orsay, France
    J Bacteriol 189:8537-45. 2007
    Although flavin-dependent ThyX proteins show thymidylate synthase activity in vitro and functionally complement thyA defects in heterologous systems, direct proof of their cellular functions is missing...
  82. ncbi Significance of thymidylate synthase gene expression level in patients with adenocarcinoma of the lung
    Hiroshi Hashimoto
    Department of Surgery II, National Defense Medical College, Saitama, Japan
    Cancer 106:1595-601. 2006
    b>Thymidylate synthase (TS) catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) and is a key enzyme for DNA synthesis...
  83. ncbi Structure-based discovery of inhibitors of thymidylate synthase
    B K Shoichet
    Department of Pharmaceutical Chemistry, University of California, San Francisco 94143
    Science 259:1445-50. 1993
    ..Chemical Directory, a database of commercially available compounds, for molecules that are complementary to thymidylate synthase (TS), a chemotherapeutic target...
  84. ncbi Thymidyl biosynthesis enzymes as antibiotic targets
    Anatoly Chernyshev
    Department of Chemistry, University of Iowa, Iowa City, IA 52242 1294, USA
    Appl Microbiol Biotechnol 74:282-9. 2007
    The two long-known "classical" enzymes of uridyl-5-methylation, thymidylate synthase and ribothymidyl synthase, have been joined by two alternative methylation enzymes, flavin-dependent thymidylate synthase and folate-dependent ..
  85. ncbi Thymidylate synthase (TS) gene expression in primary lung cancer patients: a large-scale study in Japanese population
    F Tanaka
    Second Department of Surgery, University of Environmental and Occupational Health, Kitakakyushu, Japan
    Ann Oncol 22:1791-7. 2011
    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.
  86. ncbi Phenotypic enhancement of thymidylate synthetase pathway inhibitors following ablation of Neil1 DNA glycosylase/lyase
    Lorena Taricani
    Merck Research Laboratory, Palo Alto, CA, USA
    Cell Cycle 9:4876-83. 2010
    ..These data suggest Neil1 may be a critical mediator of BER of incorporated dUMP following TS pathway inhibition...
  87. ncbi Association between dietary folate intake and clinical outcome in head and neck squamous cell carcinoma
    D Kawakita
    Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
    Ann Oncol 23:186-92. 2012
    The association between dietary folate intake, two polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS), and survival in head and neck squamous cell carcinoma (HNSCC) patients is not clarified.
  88. pmc Thymineless death in colon carcinoma cells is mediated via fas signaling
    J A Houghton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA
    Proc Natl Acad Sci U S A 94:8144-9. 1997
    ..We have developed human colon carcinoma cell models deficient in thymidylate synthase that demonstrate acute (TS- cells) or delayed (Thy4 cells) apoptosis following DNA damage induced by ..
  89. ncbi Synthesis and evaluation of 5-substituted 2'-deoxyuridine monophosphate analogues as inhibitors of flavin-dependent thymidylate synthase in Mycobacterium tuberculosis
    Martin Kögler
    Katholieke Universiteit Leuven, Rega Institute for Medical Research, Leuven, Belgium
    J Med Chem 54:4847-62. 2011
    ..has been synthesized and evaluated as potential inhibitors of mycobacterial ThyX, a novel flavin-dependent thymidylate synthase in Mycobacterium tuberculosis...
  90. pmc Design, synthesis, and biological evaluation of classical and nonclassical 2-amino-4-oxo-5-substituted-6-methylpyrrolo[3,2-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors
    Aleem Gangjee
    Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, Pennsylvania 15282, USA
    J Med Chem 51:68-76. 2008
    ..d]pyrimidin-5-yl)methyl]benzoyl}- l-glutamic acid 4 and 11 nonclassical analogues 5- 15 as potential dual thymidylate synthase (TS) and dihydrofolate reductase (DHFR) inhibitors...
  91. ncbi Polymorphism of thymidylate synthase gene and chemosensitivity of 5-fluorouracil regimen in metastatic gastrointestinal cancer
    Yue Hong Cui
    Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
    J Dig Dis 10:118-23. 2009
    To explore the polymorphism of thymidylate synthase (TS) gene and chemosensitivity of a 5-fluorouracil (5-FU)-containing regimen in metastatic colorectal and gastric cancer.
  92. ncbi Thymidine kinase, thymidylate synthase, and dihydropyrimidine dehydrogenase profiles of cell lines of the National Cancer Institute's Anticancer Drug Screen
    J L Grem
    Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute at the National Naval Medical Center, Bethesda, Maryland 20889, USA
    Clin Cancer Res 7:999-1009. 2001
    ..b>Thymidylate synthase (TS) protein expression was determined by Western analysis...
  93. pmc Mycobacterium tuberculosis thymidylate synthase gene thyX is essential and potentially bifunctional, while thyA deletion confers resistance to p-aminosalicylic acid
    Amanda S Fivian-Hughes
    Division of Mycobacterial Research, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
    Microbiology 158:308-18. 2012
    b>Thymidylate synthase (TS) enzymes catalyse the biosynthesis of deoxythymidine monophosphate (dTMP or thymidylate), and so are important for DNA replication and repair...
  94. ncbi Collateral sensitivity to novel thymidylate synthase inhibitors correlates with folate cycle enzymes impairment in cisplatin-resistant human ovarian cancer cells
    Gaetano Marverti
    Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, University of Modena and Reggio Emilia, Via Campi 287, 41100 Modena, Italy
    Eur J Pharmacol 615:17-26. 2009
    ..In this resistant line, which showed elevated expression of the folate cycle enzymes, thymidylate synthase (TS) and dihydrofolate reductase (DHFR), due to cisplatin-resistance phenotype, collateral sensitivity ..
  95. ncbi TYMS, MTHFR, p53 and MDR1 gene polymorphisms in breast cancer patients treated with adjuvant therapy
    Luis Alberto Henríquez-Hernández
    Clinical Science Department, Universidad de Las Palmas de Gran Canaria, Spain
    Cancer Epidemiol 34:490-3. 2010
    ..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...
  96. pmc Cellular pharmacology of multi- and duplex drugs consisting of ethynylcytidine and 5-fluoro-2'-deoxyuridine
    Irene V Bijnsdorp
    Department Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
    Invest New Drugs 29:248-57. 2011
    ..3 nM), resistance due to thymidine kinase (TK) deficiency was greatly reduced. The prodrugs inhibited thymidylate synthase (TS) in FM3A/0 cells (80-90%), but to a lower extent in FM3A/TK(-) (10-50%)...
  97. ncbi p53, deleted in colorectal cancer gene, and thymidylate synthase as predictors of histopathologic response and survival in low, locally advanced rectal cancer treated with preoperative adjuvant therapy
    Robyn P M Saw
    Department of Surgery, Royal Prince Alfred Hospital, Sydney, Australia
    Dis Colon Rectum 46:192-202. 2003
    ..three potential molecular genetic markers of prognosis (p53, deleted in colorectal cancer gene, and thymidylate synthase) in Dukes Stage B and C low rectal tumors treated with adjuvant therapy and to determine whether they ..
  98. ncbi Methylenetetrahydrofolate reductase (MTHFR) C677T and thymidylate synthase promoter (TSER) polymorphisms in Indonesian children with and without leukemia
    Elisa Giovannetti
    Department of Medical Oncology, VU Institute for Cancer and Immunology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
    Leuk Res 32:19-24. 2008
    Genetic variations in the polymorphic tandem repeat sequence of the enhancer region of the thymidylate synthase promoter (TSER), as well as in methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, influence methotrexate ..
  99. ncbi Anticancer antifolates: current status and future directions
    John J McGuire
    Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Curr Pharm Des 9:2593-613. 2003
    ..design studies, two new classes of antifolate enzyme inhibitors were elaborated-direct inhibitors of thymidylate synthase (TMPS) and direct inhibitors of one or both of the two folate-dependent enzymes of de novo purine synthesis...
  100. pmc Defining the role of mutations in Plasmodium vivax dihydrofolate reductase-thymidylate synthase gene using an episomal Plasmodium falciparum transfection system
    Alyson M Auliff
    Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Weary Dunlop Drive, Gallipoli Barracks, Enoggera, QLD 4051, Australia
    Antimicrob Agents Chemother 54:3927-32. 2010
    ..throughout Australasia and is caused by point mutations within the parasite dihydrofolate reductase (DHFR)-thymidylate synthase. Several unique mutations have been reported in P...
  101. ncbi Germline polymorphisms may act as predictors of response to preoperative chemoradiation in locally advanced T3 rectal tumors
    Karen Lise G Spindler
    Department of Oncology, Vejle Hospital, Vejle, Denmark
    Dis Colon Rectum 50:1363-9. 2007
    ..This study was designed to investigate the predictive value of a new combination of three gene polymorphisms: thymidylate synthase, epidermal growth factor receptor Sp1-216, and epidermal growth factor A61G.

Research Grants67

  1. Folate Status, Genomic Uracil, and the Balance of Base Excision Repair Activity
    Michael D Wyatt; Fiscal Year: 2011
    ..In particular, N5,N10 methylene tetrahydrofolate is required by thymidylate synthase to convert dUMP to TMP, which is the only de novo source of TMP...
  2. Correlative Studies for NCI Study#7916: Phase I Clinical Trial of Intravenous FAU
    Patricia Mucci LoRusso; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): The thymidylate synthase (TS) inhibitor 5-fluorouracil (5FU) is the "backbone" of cancer treatment in many malignancies. Unfortunately, tumors can be resistant to 5FU due to upregulation of TS...
  3. Inhibition of IGF-1R: A Therapeutic Strategy for Colon Cancer Stem-like Cells
    Bhaumik B Patel; Fiscal Year: 2013
    ..At the same time, expression of thymidylate synthase (TS), the putative target of miR-215, as well as integrin alpha-V (CD51) and myeloid cell leukemia-1 (MCL-1)..
  4. Identification of post-transcriptionally regulated targets by TrIP-Chip/Seq
    Jingfang Ju; Fiscal Year: 2013
    ..Our recent studies revealed that miR-215 is involved in regulating some key anticancer targets, e.g. thymidylate synthase and dihydrofolate reductase...
  5. The Role of Dynamics in Enzyme Mechanism and Inhibition
    Andrew L Lee; Fiscal Year: 2013
    ..paired with small molecule synthesis and steady-state kinetics, will be applied to a 64 kD enzyme, thymidylate synthase (TS), from E. coli...
  6. Stromal modulation of response to Thymidylate synthase inhibitors
    MARIA MARJORETTE PENA; Fiscal Year: 2013
    ..Inhibitors of the enzyme thymidylate synthase (TS), particularly fluoropyrimidines, have been used for many years in the clinical management of a variety ..
  7. THYMIDYLATE SYNTHASE AND FLUORODEOXYURIDINE RESISTANCE
    Franklin G Berger; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Thymidylate synthase (TS) catalyzes the reductive methylation of dUMP to dTMP, a reaction that is essential for the de novo biosynthesis of dTTP for DNA replication and cell proliferation...
  8. Optimization of pyrimidinyl prodrugs (PYPs) for malaria chemotherapy
    PRADIPSINH RATHOD; Fiscal Year: 2009
    ..hit: Over the last two decades, the PI has systematically considered multiple ways to attack malarial thymidylate synthase with nanomolar-level enzyme inhibitors active in whole cell assays...
  9. Conotruncal defects: genetic and nutritional risk
    EDWARD JAMES LAMMER; Fiscal Year: 2010
    ..reductase, betaine homocysteine methyltransferases 1&2, N-acetyltransferase 1, and thymidylate synthase);2) studying genetic variation of two folate transporters, folate receptor-alpha and reduced folate carrier;..
  10. Discovery of novel PCFT-targeted agents
    Larry H Matherly; Fiscal Year: 2013
    ..Another cytotoxic hPCFT substrate, AG112, was a potent inhibitor of thymidylate synthase. AG71 was tested in vivo against subcutaneous human hepatoma cells in SCID mice and showed potent hPCFT-..
  11. Mechanisms of Cytotoxicity and Radiosensitization for Antimetabolites
    Donna S Shewach; Fiscal Year: 2013
    ..as hydroxyurea (ribonucleotide reductase inhibitor), and fluorodeoxyuridine, methotrexate and pemetrexed (thymidylate synthase inhibitors) to produce the first unifying hypothesis for antimetabolite radiosensitization...
  12. Prognostic Molecular Markers of Colorectal Cancer
    Upender Manne; Fiscal Year: 2009
    ..in colon cancer), p53, p21waf-1, p27Kip-1, Mdm2, cyclin E, Ki67, Bcl-2, Bax, MUC1, cyclooxygenase 2, and thymidylate synthase. The extent of apoptosis will be determined utilizing TUNEL...
  13. Chemotherapy targeting human thymidylate synthase messenger RNA
    THOMAS C HERMANN; Fiscal Year: 2013
    ..The proposed research is intended to discover novel anti-cancer agents that inhibit expression of thymidylate synthase (TS), the sole intracellular de novo source of thymidylate for DNA biosynthesis...
  14. Genetic determinants associated with pemetrexed response and toxicity
    M Eileen Dolan; Fiscal Year: 2013
    ..The most significant interaction at clinically achievable concentrations is with thymidylate synthase (TYMS), although the drug is known to target at least two other folate dependent enzymes...
  15. CELLULAR EFFECTS OF INHIBITION OF THYMIDYLATE SYNTHASE
    RICHARD MORAN; Fiscal Year: 1993
    Inhibition of the key enzyme thymidylate synthase (TS) is a major cause of the activity of 5-fluorouracil (5-FU) as a cancer chemotherapeutic agent...
  16. CYCLIC NUCLEOTIDES, CYCLOPHOSPHAMIDES, AND ANTIVIRALS
    WESLEY BENTRUDE; Fiscal Year: 1993
    ..prodrug delivery of known or potential antivirals and antitumor agents, with a focus on previously targeted thymidylate synthase in thymidine kinase-deficient drug- resistant HSV-1 mutants; and, 2) potential cAMP or cGMP antagonist/..
  17. NOVEL TREATMENT OF REFRACTORY GI MALIGNANCIES
    Scott Wadler; Fiscal Year: 1999
    ..these agents on mRNA, protein levels and activity for the target enzymes, ribonucleotide reductase (RR) and thymidylate synthase (TS), were performed in vitro which demonstrated a positive interaction between 5FU + HU + IFN...
  18. Tunneling and Dynamics in Enzyme Catalyzed Reactions
    Amnon Kohen; Fiscal Year: 2012
    ..A mechanistic investigation of C-H bond activation in alternative dihydrofolate reductases (DHFRs) and thymidylate synthase (TSase) will be conducted...
  19. EDITING OF THYMIDYLATE SYNTHASE RNA
    BRUCE DOLNICK; Fiscal Year: 2002
    b>Thymidylate synthase is the enzyme responsible for the de novo synthesis of thymidylate and is a major target in chemotherapy...
  20. Molecular Correlates--Oxaliplatin/5FU/XRT, Esophageal CA
    Lakshmi Pendyala; Fiscal Year: 2002
    ..after therapy with 5FU (colon cancer) or 5FU/cisplatin (gastric cancer) are inversely associated with thymidylate synthase (TS), dihydropyrmidine dehydrogenase (DPD) and the excision repair cross-complementing-1 (ERCC-1) gene ..
  21. STRUCTURE BASED DRUG DESIGN
    Robert Stroud; Fiscal Year: 2004
    ..The essential enzyme function is the well recognized anti-cancer target, human thymidylate synthase (TS), the rate-limiting enzyme that provides the sole de novo pathway for synthesis of the DNA-base dTMP ..
  22. CELLULAR PHARMACOLOGY OF THE STEREOISOMERS OF LEUCOVORIN
    Richard Schilsky; Fiscal Year: 1991
    ..reductive cleavage of folates and HPLC chromatography of p-aminobenzoyl polyglutamates; assessment of thymidylate synthase activity by incorporation of (3H) deoxyuridine into DNA; and the use of a novel photoactive analogue of ..
  23. TUMOR MARKERS TO PREDICT TREATMENT RESPONSE
    Lynn Dressler; Fiscal Year: 2005
    ..Two subcontracts are included in this proposal, one to support the CALGB Pathology Coordinating Office functions at OSU relevant to this study and the other in support of the molecular studies being performed by USC. ..
  24. PET IMAGING OF DRUG KINETICS AND PATHWAYS
    Anthony Shields; Fiscal Year: 2002
    ..an antimetabolite that is incorporated into DNA after sequential activation by thymidine kinase 1 (TK) and thymidylate synthase (TS)...
  25. Molecular Approach in Predicting 5-Fluorouracil Efficacy
    Robert Diasio; Fiscal Year: 2005
    ..could be identified by quantitating the expression levels of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS). The specific aims of the current application include: Spec...
  26. MOLECULAR AND ELECTRONIC STRUCTURES OF ANTIFOLATE DRUGS
    Vivian Cody; Fiscal Year: 1991
    ..biological mechanisms regulating folate-dependent enzymes, in particular dihydrofolate reductase (DHFR) and thymidylate synthase (TS)...
  27. QUORUM SENSING IN HUMAN CELLS
    BRUCE DOLNICK; Fiscal Year: 2002
    ..previously discovered in our laboratory, produces a naturally occurring antisense RNA (rTSalpha) to human thymidylate synthase (TS) RNAs and two proteins (rTSalpha and rTSbeta)...
  28. QUORUM SENSING IN HUMAN CELLS
    BRUCE DOLNICK; Fiscal Year: 2003
    ..previously discovered in our laboratory, produces a naturally occurring antisense RNA (rTSalpha) to human thymidylate synthase (TS) RNAs and two proteins (rTSalpha and rTSbeta)...
  29. NCI OUTSTANDING INVESTIGATORS GRANT
    Frank Maley; Fiscal Year: 2000
    Because of the role that thymidylate synthase (TS) and deoxycytidylate deaminase (DD) play in providing nucleotide products for DNA synthesis, they have become prime targets for chemotherapy...
  30. MOLECULAR PROGNOSTIC INDICATORS IN COLORECTAL CANCER
    Leonard Saltz; Fiscal Year: 2000
    ..Recent data from the laboratory of Dr. Peter Danenberg indicate that a high relative expression of thymidylate synthase mRNA (determined by quantitative RT-PCR) strongly predicts for failure to respond to FU/LV...
  31. RTS AND ITS ROLE IN CHEMOTHERAPY
    BRUCE DOLNICK; Fiscal Year: 1999
    ..rTS is a gene which overlaps the human thymidylate synthase (TS) gene and is encoded by the opposite strand of DNA...
  32. PROTECTION OF HOST TISSUES FROM FDURD TOXICITY
    Jonathan Maybaum; Fiscal Year: 2002
    ..that this sclerosis is caused by the direct injury of biliary epithelium due to drug-induced inhibition of thymidylate synthase (TS)...
  33. RELATION OF THYMIDYLATE SYNTHASE STRUCTURE TO FUNCTION
    JAMES APPLEMAN; Fiscal Year: 1992
    b>Thymidylate synthase (TS) catalyzes the conversion of dUMP and [6R]-5,10- methylenetetrahydrofolate (CH2H4folate) to dTMP and H2folate by reductive methylation, in which CH2H4folate is both methyl donor and reducing agent...
  34. THYMIDYLATE SYNTHASE GENE EXPRESSION
    Lee Johnson; Fiscal Year: 2002
    b>Thymidylate synthase (TS) is an essential enzyme in proliferating cells and an important target of chemotherapeutic drugs...
  35. MULTISUBSTRATE ENZYME INHIBITORS
    ARTHUR BROOM; Fiscal Year: 1991
    The long range goals of the project are to develop potent and specific multisubstrate inhibitors of thymidylate synthase, to use these as probes to study the active site of the enzyme and to develop from this information useful new ..
  36. FLUOROPYRIMIDINE RESPONSE MODULATION BY FOLINIC ACID
    SONDRA BERGER; Fiscal Year: 1990
    ..CF is thought to direct the action of FUra to inhibition of thymidylate synthase (TS), an enzyme pivotal in DNA biosynthesis and critical for tumor cell growth...
  37. CRYSTALLOGRAPHIC STUDIES OF THYMIDYLATE SYNTHASE
    Janet Finer Moore; Fiscal Year: 2003
    The broad objectives of the work are to understand the functions of thymidylate synthase (TS) and other nucleotide, RNA and DNA-modifying enzymes...
  38. PROGRAMMED/NONPROGRAMMED CYTOX BY FLUOROPYRIMIDINES
    Jonathan Maybaum; Fiscal Year: 1999
    ..about the consequences of modulating proteins involved in the formation of DNA lesions following thymidylate synthase inhibition (uracil-DNA-glycosylase), progression of cells though the cell cycle (p21/WAF1/Cip1) or the ..
  39. ANTIMALARIAL ACTIVITY OF OROTIC ACID ANALOGS
    PRADIPSINH RATHOD; Fiscal Year: 1993
    ..If successful in vitro, it will tell us that derivatives of dihydroorotate may also be highly effective antimalarial drugs...
  40. 5 FLUOROURACIL TARGET IN EUKARYOTIC CELLS
    David Priest; Fiscal Year: 2000
    ..application would investigate folate-based control of CpG site methylation in the promoter region of the thymidylate synthase gene leading to attenuation of expression...
  41. The Yeast Exosome as a Model Anticancer Drug Target
    James Butler; Fiscal Year: 2004
    ..8S rRNA processing. These experiments should clarify the connection between 5FU and rRNA processing and therefore provide a new pathway to which anticancer drugs can be targeted. ..
  42. THE MECHANISM OF ACTION OF THYMIDYLATE SYNTHETASE
    R Dunlap; Fiscal Year: 1980
    ....
  43. A Molecular Approach For Opportunistic HIV-1 Infections
    Karen Anderson; Fiscal Year: 2007
    ..Two enzymes crucial for DNA synthesis and one-carbon transfers are thymidylate synthase and dihydrofolate reductase...
  44. SYNTHESIS OF NOVEL THYMIDYLATE SYNTHASE INHIBITORS
    Robert Kempton; Fiscal Year: 1992
    ..b>Thymidylate synthase (TS, EC 2.1.1...
  45. PROTEIN STRUCTURE-FUNCTION STUDIES USING UAG SUPPRESSORS
    Jeffrey Miller; Fiscal Year: 1993
    ..Additional experiments, including the use of second-site revertants, will be employed to pinpoint important contacts in the protein, as will attempts to change the specificity of ligand binding for each protein under study...
  46. Thymidylate Synthases: Modes of Catalysis and Inhibition
    Lukasz Lebioda; Fiscal Year: 2009
    The enzyme, thymidylate synthase (TS) catalyzes the reaction that produces thymidylate (TMP). Depletion of TMP by inhibition of TS results in death of rapidly dividing cells, such as cancer cells...
  47. GENE INTERACTIONS IN COLON CANCER
    Leonard Augenlicht; Fiscal Year: 2003
    ..c-myc may influence outcome in at least 3 ways: both c-myc and thymidylate synthase (TS) bind TS protein and are translationally regulated by formation of these ribonucleoprotein structures, ..
  48. Novel Single, Dual and Multitargeted Inhibitors of RTKs
    Aleem Gangjee; Fiscal Year: 2007
    ..abstract_text> ..
  49. MOLECULAR PROGNOSTIC INDICATORS IN ESOPHAGEAL CANCER
    Peter Danenberg; Fiscal Year: 2001
    ..The applicant will investigate the association between intratumoral expressions of thymidylate synthase, ERCC1, thymidine phosphorylase, bcl-2, bax and the p53 mutational status in esophageal squamous cell ..
  50. CRYPTOSPORIDIUM DHFR AS A CHEMOTHERAPEUTIC TARGET
    Richard Nelson; Fiscal Year: 1999
    ..are the parasite dihydropteroate synthase (DHPS) and, in protozoa, the bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS)...
  51. STRUCTURE BASED ANALOGS AS ANTIOPPORTUNISTIC AGENTS
    Aleem Gangjee; Fiscal Year: 2001
    ..The analogues synthesized will also be submitted for screening against tuberculosis (NIAID) parasitic diseases (WHO) and tumor cells in culture (NCI). ..
  52. Third Generation Antiopportunistic Agents
    Aleem Gangjee; Fiscal Year: 2003
    ..Screening against tuberculosis (NIAID) and tumor cells in culture (NCI) is also proposed. ..
  53. NOVEL NONINDUCIBLE THYMIDYLATE SYNTHASE INHIBITORS
    Aleem Gangjee; Fiscal Year: 2004
    ..Recent studies indicate that the clinically used TS inhibitors 5FU, 5FdR, AD1694, and LY23154 all induce thymidylate synthase (TS) synthesis...
  54. Alpha Folate Receptor Mediated GARFTase Inhibitors as Selective Antitumor Agents
    Aleem Gangjee; Fiscal Year: 2010
    ....
  55. Single Agents with Designed Combination Chemotherapy Potential
    Aleem Gangjee; Fiscal Year: 2010
    ..that each inhibit VEGFR-2 and PDGFR-$, (tumor angiogenic effects) and remarkably also inhibit human thymidylate synthase (hTS) (cytotoxic effects)...
  56. DRUG SYNERGY WITH ANTIFOLATE COMBINATIONS
    John Galivan; Fiscal Year: 1990
    ..studies have shown the dihydrofolate reductase (DHFR) inhibitors can be combined with a folate based thymidylate synthase (TS) inhibitor (N10-propartyl-5,8- dideazafolate, PDDF) to yield synergistic tumor cell growth inhibition ..
  57. rTS Signaling Mimetics As Novel Cancer Therapeutics
    Jie Wang; Fiscal Year: 2006
    ..applicant): The Dolnick laboratory recently reported a novel signaling pathway governing both the level of thymidylate synthase protein (TS) and the cytoskeleton function in human cancer cells...
  58. Antitumor Antimitotics That Reverse Tumor Resistance
    Aleem Gangjee; Fiscal Year: 2010
    ..The study will also further define the mechanism of action of the novel series and could afford agents for clinical use. ..
  59. Novel, P. jirovecii Specific Antipneumocystis Agents
    Aleem Gangjee; Fiscal Year: 2009
    ..These agents could be used alone or in combination to treat PCP thus providing novel agents against a new target. ..
  60. MECHANISMS OF DTMP SYNTHASE AND DCMP HYDROXYMETHLYLASE
    LARRY HARDY; Fiscal Year: 1993
    b>Thymidylate synthase (TS) is an essential enzyme for DNA synthesis and is a target for anticancer and antimicrobial drugs...
  61. APTAMER BASED BACTERIAL INHIBITION SYSTEM
    Jonathan Blum; Fiscal Year: 2001
    ..the analysis of these aptamers, including some which inhibit an enzyme required for nucleotide metabolism, thymidylate synthase, and others which interfere with bacterial growth...
  62. DTMP SYNTHASE: NMR AND MECHANISTIC STUDIES
    R Dunlap; Fiscal Year: 1991
    ..of this proposal is the use of NMR, mechanistic strategies, and immunochemical approaches to study thymidylate synthase which catalyses the 5, 10-methylenetetrahydrofolate- dependent reductive methylation of deoxyuridylate to ..
  63. THYMIDYLATE SYNTHASE INHIBITORS IN HEAD AND NECK CANCER
    Youcef Rustum; Fiscal Year: 2000
    ..The proposed studies are expected to provide a rational basis for the design of clinical protocols in head and neck cancer. ..
  64. NON INVASIVE MEASUREMENT OF THYMIDYLATE SYNTHASE INHIBIT
    Patricia Price; Fiscal Year: 2001
    DESCRIPTION: (Applicant's Description) Thymidylate synthase (TS) is the target of several anticancer agents due its important role in the de novo synthesis of DNA...
  65. Prognostic Markers in Trials for Head and Neck Cancer
    Kevin Cullen; Fiscal Year: 2005
    Our fundamental hypothesis is that readily identifiable biomarkers, including p53, thymidylate synthase and enzymes in the glutathione pathway are critical determinants of response and long term outcome for patients receiving chemotherapy ..
  66. SITE-DIRECTED DRUG DISCOVERY
    James Wells; Fiscal Year: 2002
    ..This method was applied to generate a potent and novel inhibitor for thymidylate synthase, an essential enzyme in pyrimidine metabolism with therapeutic applications in cancer and infectious ..
  67. PROGNOSTIC INDICATORS IN LOCALIZED COLON CANCER
    HEINZ LENZ; Fiscal Year: 1999
    ..The applicant's preliminary findings indicate that overexpression of thymidylate synthase (TS), an enzyme necessary for DNA synthesis, is a strong predictor for recurrence in patients with stage II ..