Genomes and Genes
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 22.214.171.124.
Publications369 found, 100 shown here
- 5-fluorouracil: mechanisms of action and clinical strategiesDaniel 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...
- Thymidylate synthase as a determinant of pemetrexed sensitivity in non-small cell lung cancerK 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. 2011Although 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 ..
- ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapyY Shirota
University of Southern California/Norris Comprehensive Cancer Center and Response Genetics Inc, Los Angeles, CA 90033, USA
J Clin Oncol 19:4298-304. 2001PURPOSE: 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)/..
- Thymidylate synthase expression and prognosis in colorectal cancer: a systematic review and meta-analysisSanjay Popat
Section of Cancer Genetics, Institute of Cancer Research, Sutton SM2 5NG, UK
J Clin Oncol 22:529-36. 2004A number of studies have investigated the relationship between thymidylate synthase (TS) expression and survival in colorectal cancer (CRC) patients...
- Thymidylate synthase and dihydrofolate reductase expression in non-small cell lung carcinoma: the association with treatment efficacy of pemetrexedChung 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. 2011b>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)...
- Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFOX-4 chemotherapyAnnamaria Ruzzo
Institute of Biochemistry G Fornaini, University of Urbino, Urbino, Italy
J Clin Oncol 25:1247-54. 2007....
- Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumorsP G Johnston
NCI Navy Medical Oncology Branch, National Institutes of Health, Bethesda, Maryland 20889 5105
Cancer Res 55:1407-12. 1995b>Thymidylate synthase (TS) is the target enzyme for 5-fluorouracil (5-FU)...
- Significance of thymidylate synthase and thyroid transcription factor 1 expression in patients with nonsquamous non-small cell lung cancer treated with pemetrexed-based chemotherapyJong 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. 2011This 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 ..
- Thymidylate synthase expression and genotype have no major impact on the clinical outcome of colorectal cancer patients treated with 5-fluorouracilMarina 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. 2011b>Thymidylate synthase (TS) expression levels appear to be related to response to 5-fluorouracil-(5-FU)-based chemotherapy in colorectal cancer (CRC) patients...
- Thymidylate synthase and ERCC1 as predictive markers in patients with pulmonary adenocarcinoma treated with pemetrexed and cisplatinSeung 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. 2013Increased expression of thymidylate synthase (TS) is thought to be associated with resistance to antifolate drugs such as pemetrexed...
- 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 synthaseTakafumi 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...
- A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levelsMichael 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. 2004A 6 bp deletion polymorphism in the thymidylate synthase (TS) gene was investigated in order to determine its function.
- Identification and functional analysis of single nucleotide polymorphism in the tandem repeat sequence of thymidylate synthase geneKazuyuki Kawakami
Department of Surgery, Kanazawa University School of Medicine, Kanazawa 920 8641, Japan
Cancer Res 63:6004-7. 2003The 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...
- Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritisThierry 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)...
- miR-192/miR-215 influence 5-fluorouracil resistance through cell cycle-mediated mechanisms complementary to its post-transcriptional thymidilate synthase regulationValentina Boni
Oncology Unit, Casa Sollievo Sofferenza, S Giovanni Rotondo, Italy
Mol Cancer Ther 9:2265-75. 2010b>Thymidylate synthase (TYMS) is a target of the most widely used chemotherapeutic agents against gastrointestinal malignancies, the fluoropyrimidine-based therapy...
- Thymidylate synthase but not excision repair cross-complementation group 1 tumor expression predicts outcome in patients with malignant pleural mesothelioma treated with pemetrexed-based chemotherapyLuisella 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. 2010The relationship between thymidylate synthase (TS) expression and outcome in patients with malignant pleural mesothelioma (MPM) treated with pemetrexed (P) was retrospectively evaluated.
- Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancerH 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 ..
- The catalytic mechanism and structure of thymidylate synthaseC W Carreras
Department of Pharmaceutical Chemistry, University of California San Francisco 94143 0448, USA
Annu Rev Biochem 64:721-62. 1995b>Thymidylate synthase (TS, EC 126.96.36.199) 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...
- Induction of thymidylate synthase as a 5-fluorouracil resistance mechanismG 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. 2002b>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...
- Role of genetic and nongenetic factors for fluorouracil treatment-related severe toxicity: a prospective clinical trial by the German 5-FU Toxicity Study GroupMatthias Schwab
Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, University of Stuttgart, Stuttgart, Germany
J Clin Oncol 26:2131-8. 2008To 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 ..
- Cloning, expression, and characterization of Babesia gibsoni dihydrofolate reductase-thymidylate synthase: inhibitory effect of antifolates on its catalytic activity and parasite proliferationGabriel 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. 2008Dihydrofolate 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...
- Predictive value of thymidylate synthase expression in advanced colorectal cancer patients receiving fluoropyrimidine-based chemotherapy: evidence from 24 studiesLi Xin Qiu
Cancer Center, Nanjing Drum Tower Hospital, Nanjing Medical University, Nanjing, China
Int J Cancer 123:2384-9. 2008The published data about thymidylate synthase (TS) expression and its predictive value in advanced colorectal cancer (CRC) patients receiving fluoropyrimidine-based chemotherapy seemed inconclusive...
- Mechanisms of acquired chemoresistance to 5-fluorouracil and tomudex: thymidylate synthase dependent and independent networksWeiguang Wang
Research Institute in Healthcare Science, School of Applied Sciences, University of Wolverhampton, Wolverhampton, WV1 1SB, UK
Cancer Chemother Pharmacol 59:839-45. 2007b>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.
- Immunohistochemical demonstration of fluoropyrimidine-metabolizing enzymes in various types of cancerShingo 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)...
- Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphism in normal tissue as predictors of fluorouracil sensitivityAnders Jakobsen
Danish Colorectal Cancer, Group South, Vejle Hospital, 7100 Vejle, Denmark
J Clin Oncol 23:1365-9. 2005To analyze thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with respect to fluorouracil (FU) sensitivity.
- Case-control analysis of thymidylate synthase polymorphisms and risk of lung cancerQiuling 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 ..
- Thymidylate synthase gene polymorphism predicts toxicity in colorectal cancer patients receiving 5-fluorouracil-based chemotherapyThierry Lecomte
Service de Gastroenterologie, Assistance Publique Hopitaux de Paris, Hopital Europeen Georges Pompidou, Paris
Clin Cancer Res 10:5880-8. 2004The target enzyme for 5-fluorouracil (5-FU) is thymidylate synthase (TS)...
- Human thymidylate synthase is in the closed conformation when complexed with dUMP and raltitrexed, an antifolate drugJ Phan
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 92908, USA
Biochemistry 40:1897-902. 2001b>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...
- Prognostic value of thymidylate synthase expression in patients with p-stage I adenocarcinoma of the lungTatsuo 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. 2002We 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...
- 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 trialMarianne 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...
- Prognostic and predictive value of thymidylate synthase expression in primary colorectal cancerM Karlberg
Department of Oncology and Pathology, CCK R8 03, Karolinska University Hospital, S 171 76 Stockholm, Sweden
Anticancer Res 30:645-51. 2010To investigate thymidylate synthase (TS) expression in primary colorectal cancer (CRC) as a prognostic and predictive marker of benefit for adjuvant chemotherapy.
- Combined therapy with a thymidylate synthase-inhibiting vector and S-1 has effective antitumor activity against 5-FU-resistant tumorsKyuichi 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. 2011High levels of intratumoral thymidylate synthase (TS) expression are associated with resistance to 5-fluorourcil (5-FU)...
- 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 cancerMyung 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 ..
- Predictors of survival and toxicity in patients on adjuvant therapy with 5-fluorouracil for colorectal cancerM 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 ..
- Significance of folate receptor alpha and thymidylate synthase protein expression in patients with non-small-cell lung cancer treated with pemetrexedDaniel 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.
- Nuclear localization of de novo thymidylate biosynthesis pathway is required to prevent uracil accumulation in DNAAmanda 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...
- Gene polymorphisms in TYMS, MTHFR, p53 and MDR1 as risk factors for breast cancer: a case-control studyL 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...
- Altered tissue 3'-deoxy-3'-[18F]fluorothymidine pharmacokinetics in human breast cancer following capecitabine treatment detected by positron emission tomographyLaura M Kenny
Department of Oncology, Imperial College London, London, United Kingdom
Clin Cancer Res 15:6649-57. 2009We 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)...
- Pemetrexed indirectly activates the metabolic kinase AMPK in human carcinomasScott B Rothbart
Department of Pharmacology and Toxicology and the Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA
Cancer Res 70:10299-309. 2010The 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 ..
- Molecular genetics of para-aminosalicylic acid resistance in clinical isolates and spontaneous mutants of Mycobacterium tuberculosisVanessa 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...
- Squamous cell carcinoma of the lung compared with other histotypes shows higher messenger RNA and protein levels for thymidylate synthasePaolo Ceppi
Thoracic Oncology Unit, Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Orbassano, Torino, Italy
Cancer 107:1589-96. 2006In patients with cancer, one of the main mechanism of resistance to antimetabolite drugs is related to higher levels of thymidylate synthase (TS) activity.
- 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 cellsElisa 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...
- The role of thymidylate synthase expression in prognosis and outcome of adjuvant chemotherapy in patients with rectal cancerP G Johnston
National Cancer Institute Navy Medical Oncology Branch, National Cancer Institute, Bethesda, MD 20889
J Clin Oncol 12:2640-7. 1994We 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 ..
- P21Cip1 is a critical mediator of the cytotoxic action of thymidylate synthase inhibitors in colorectal carcinoma cellsJames 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...
- One-carbon metabolism related gene polymorphisms interact with alcohol drinking to influence the risk of colorectal cancer in JapanKeitaro 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...
- Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumorsA 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 ..
- Uracil incorporation into genomic DNA does not predict toxicity caused by chemotherapeutic inhibition of thymidylate synthaseYuhong 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. 2008b>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...
- LY231514, a pyrrolo[2,3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzymesC 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)...
- A ribosomal function is necessary for efficient splicing of the T4 phage thymidylate synthase intron in vivoK Semrad
Institute of Microbiology and Genetics, Vienna Biocenter, 1030 Wien, Austria
Genes Dev 12:1327-37. 1998Splicing 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...
- High gene expression of TS1, GSTP1, and ERCC1 are risk factors for survival in patients treated with trimodality therapy for esophageal cancerMary 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...
- Thymidylate synthase gene variations: predictive and prognostic markersGeorg 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 ..
- E2F1 overexpression correlates with thymidylate synthase and survivin gene expressions and tumor proliferation in non small-cell lung cancerCheng Long Huang
Department of Second Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
Clin Cancer Res 13:6938-46. 2007We 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).
- 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...
- Uridine diphosphate glucuronosyl transferase 1A1 promoter polymorphism predicts the risk of gastrointestinal toxicity and fatigue induced by irinotecan-based chemotherapyCristian 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 ..
- Pemetrexed (ALIMTA), a novel multitargeted antineoplastic agentAlex 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...
- 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 cellsJen 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...
- Nuclear thymidylate synthase expression, p53 expression and 5FU response in colorectal carcinomaN A Wong
Department of Pathology, University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG
Br J Cancer 85:1937-43. 2001b>Thymidylate synthase (TS) is a key enzyme in DNA synthesis and is inhibited by metabolites of the chemotherapeutic agent 5-fluorouracil (5FU)...
- Antisense-induced down-regulation of thymidylate synthase and enhanced cytotoxicity of 5-FUdR in 5-FUdR-resistant HeLa cellsP J Ferguson
Cancer Research Laboratories, London Regional Cancer Centre, London, Ontario, Canada
Br J Pharmacol 134:1437-46. 20011. Thymidylate synthase (TS) is a target for several anticancer drugs...
- Inhibition of dUTPase induces synthetic lethality with thymidylate synthase-targeted therapies in non-small cell lung cancerPeter 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. 2012Chemotherapies 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...
- New prognostic indicator for non-small-cell lung cancer, quantitation of thymidylate synthase by real-time reverse transcription polymerase chain reactionYasushi Shintani
Department of Surgery, E1, Osaka University Graduate School of Medicine, Osaka, Japan
Int J Cancer 104:790-5. 2003b>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...
- Discovery of a novel class of potent human deoxyuridine triphosphatase inhibitors remarkably enhancing the antitumor activity of thymidylate synthase inhibitorsSeiji 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...
- Pemetrexed for previously treated patients with non-small cell lung cancer and differences in efficacy according to thymidylate synthase expressionSatoshi 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...
- Associations between gene polymorphisms of thymidylate synthase with its protein expression and chemosensitivity to 5-fluorouracil in pancreatic carcinoma cellsQiang 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. 2011b>Thymidylate synthase (TS) is a key regulatory enzyme for de novo DNA synthesis...
- In vivo mutations of thymidylate synthase (encoded by thyA) are responsible for thymidine dependency in clinical small-colony variants of Staphylococcus aureusIndranil 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...
- Polymorphisms in the thymidylate synthase and dihydropyrimidine dehydrogenase genes predict response and toxicity to capecitabine-raltitrexed in colorectal cancerJosefa 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 ..
- 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-fluorouracilM C Etienne
Centre Antoine Lacassagne, Nice, France
Br J Cancer 79:1864-9. 1999The 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)...
- 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 cancerBong 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...
- Expression of thymidylate synthase in human non-small cell lung cancerY Otake
Department of Thoracic Surgery, Kyoto University Hospital
Jpn J Cancer Res 90:1248-53. 19995-Fluorouracil (5-FU) has been used worldwide, and the correlation between its effects and thymidylate synthase (TS) expression has been reported in gastrointestinal malignancy...
- Combining several polymorphisms of thymidylate synthase gene for pharmacogenetic analysisM 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. 2005b>Thymidylate synthase (TS) is an essential enzyme in proliferating cells and an important target for several chemotherapeutics...
- Thymidilate synthase expression predicts longer survival in patients with stage II colon cancer treated with 5-flurouracil independently of microsatellite instabilityMarisa 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 ..
- Preoperative chemoradiation for rectal cancer using capecitabine and celecoxib correlated with posttreatment assessment of thymidylate synthase and thymidine phosphorylase expressionKeith R Unger
Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia 22908, USA
Int J Radiat Oncol Biol Phys 80:1377-82. 2011b>Thymidylate synthase (TS) and thymidine phosphorylase (TP) expression have been shown to be predictors of response to therapy...
- Structure of an RNA dimer of a regulatory element from human thymidylate synthase mRNASergey 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. 2011A 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...
- Kinetics and ligand-binding preferences of Mycobacterium tuberculosis thymidylate synthases, ThyA and ThyXJoshua 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...
- RAD001 shows activity against gastric cancer cells and overcomes 5-FU resistance by downregulating thymidylate synthaseKyung 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)...
- Reexamining a proposal: thymidylate synthase 5'-untranslated region as a regulator of translation efficiencySoma Ghosh
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA
Cancer Biol Ther 12:750-5. 2011The DNA replicative gene, thymidylate synthase (TYMS), is inhibited upon treatment with the anticancer drug 5-fluorouracil (5FU)...
- Cooperation between an intrinsically disordered region and a helical segment is required for ubiquitin-independent degradation by the proteasomeSandra 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...
- Alternative thymidylate synthase, ThyX, involved in Corynebacterium glutamicum ATCC 13032 survival during stationary growth phaseMijeong Park
Department of Biology, Kyung Hee University, Seoul, Korea
FEMS Microbiol Lett 307:128-34. 2010A BLASTP search has shown the presence of a gene homologous to an alternative thymidylate synthase (TS), thyX, in Corynebacterium glutamicum ATCC 13032...
- Prognostic significance of miR-215 in colon cancerMihriban Karaayvaz
Department of Pathology, State University of New York at Stony Brook, Stony Brook, NY 11794 8691, USA
Clin Colorectal Cancer 10:340-7. 2011We 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...
- 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. 2004Many 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...
- 2-[11C]thymidine positron emission tomography as an indicator of thymidylate synthase inhibition in patients treated with AG337Paula Wells
Imperial College School of Medicine, Hammersmith Hospital, London, UK
J Natl Cancer Inst 95:675-82. 2003Some 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...
- Flavin-dependent thymidylate synthase ThyX activity: implications for the folate cycle in bacteriaDamien Leduc
Inserm Avenir Group, Institut de Génétique et de Microbiologie, CNRS UMR8621, F 91405 Orsay, France
J Bacteriol 189:8537-45. 2007Although 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...
- Significance of thymidylate synthase gene expression level in patients with adenocarcinoma of the lungHiroshi Hashimoto
Department of Surgery II, National Defense Medical College, Saitama, Japan
Cancer 106:1595-601. 2006b>Thymidylate synthase (TS) catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) and is a key enzyme for DNA synthesis...
- Structure-based discovery of inhibitors of thymidylate synthaseB 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...
- Thymidyl biosynthesis enzymes as antibiotic targetsAnatoly Chernyshev
Department of Chemistry, University of Iowa, Iowa City, IA 52242 1294, USA
Appl Microbiol Biotechnol 74:282-9. 2007The 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 ..
- Thymidylate synthase (TS) gene expression in primary lung cancer patients: a large-scale study in Japanese populationF Tanaka
Second Department of Surgery, University of Environmental and Occupational Health, Kitakakyushu, Japan
Ann Oncol 22:1791-7. 2011Previous 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.
- Phenotypic enhancement of thymidylate synthetase pathway inhibitors following ablation of Neil1 DNA glycosylase/lyaseLorena 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...
- Association between dietary folate intake and clinical outcome in head and neck squamous cell carcinomaD Kawakita
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
Ann Oncol 23:186-92. 2012The 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.
- Thymineless death in colon carcinoma cells is mediated via fas signalingJ 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 ..
- Synthesis and evaluation of 5-substituted 2'-deoxyuridine monophosphate analogues as inhibitors of flavin-dependent thymidylate synthase in Mycobacterium tuberculosisMartin 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...
- 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 inhibitorsAleem 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...
- Polymorphism of thymidylate synthase gene and chemosensitivity of 5-fluorouracil regimen in metastatic gastrointestinal cancerYue Hong Cui
Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
J Dig Dis 10:118-23. 2009To explore the polymorphism of thymidylate synthase (TS) gene and chemosensitivity of a 5-fluorouracil (5-FU)-containing regimen in metastatic colorectal and gastric cancer.
- Thymidine kinase, thymidylate synthase, and dihydropyrimidine dehydrogenase profiles of cell lines of the National Cancer Institute's Anticancer Drug ScreenJ 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...
- Mycobacterium tuberculosis thymidylate synthase gene thyX is essential and potentially bifunctional, while thyA deletion confers resistance to p-aminosalicylic acidAmanda 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. 2012b>Thymidylate synthase (TS) enzymes catalyse the biosynthesis of deoxythymidine monophosphate (dTMP or thymidylate), and so are important for DNA replication and repair...
- Collateral sensitivity to novel thymidylate synthase inhibitors correlates with folate cycle enzymes impairment in cisplatin-resistant human ovarian cancer cellsGaetano 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 ..
- TYMS, MTHFR, p53 and MDR1 gene polymorphisms in breast cancer patients treated with adjuvant therapyLuis 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...
- Cellular pharmacology of multi- and duplex drugs consisting of ethynylcytidine and 5-fluoro-2'-deoxyuridineIrene 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%)...
- 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 therapyRobyn 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 ..
- Methylenetetrahydrofolate reductase (MTHFR) C677T and thymidylate synthase promoter (TSER) polymorphisms in Indonesian children with and without leukemiaElisa 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. 2008Genetic 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 ..
- Anticancer antifolates: current status and future directionsJohn 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...
- Defining the role of mutations in Plasmodium vivax dihydrofolate reductase-thymidylate synthase gene using an episomal Plasmodium falciparum transfection systemAlyson 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...
- Germline polymorphisms may act as predictors of response to preoperative chemoradiation in locally advanced T3 rectal tumorsKaren 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.
- Folate Status, Genomic Uracil, and the Balance of Base Excision Repair ActivityMichael 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...
- Correlative Studies for NCI Study#7916: Phase I Clinical Trial of Intravenous FAUPatricia Mucci LoRusso; Fiscal Year: 2010DESCRIPTION (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...
- Inhibition of IGF-1R: A Therapeutic Strategy for Colon Cancer Stem-like CellsBhaumik 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)..
- Identification of post-transcriptionally regulated targets by TrIP-Chip/SeqJingfang 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...
- The Role of Dynamics in Enzyme Mechanism and InhibitionAndrew 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...
- Stromal modulation of response to Thymidylate synthase inhibitorsMARIA 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 ..
- THYMIDYLATE SYNTHASE AND FLUORODEOXYURIDINE RESISTANCEFranklin G Berger; Fiscal Year: 2012DESCRIPTION (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...
- Optimization of pyrimidinyl prodrugs (PYPs) for malaria chemotherapyPRADIPSINH 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...
- Conotruncal defects: genetic and nutritional riskEDWARD 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;..
- Discovery of novel PCFT-targeted agentsLarry 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-..
- Mechanisms of Cytotoxicity and Radiosensitization for AntimetabolitesDonna 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...
- Prognostic Molecular Markers of Colorectal CancerUpender 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...
- Chemotherapy targeting human thymidylate synthase messenger RNATHOMAS 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...
- Genetic determinants associated with pemetrexed response and toxicityM 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...
- CELLULAR EFFECTS OF INHIBITION OF THYMIDYLATE SYNTHASERICHARD MORAN; Fiscal Year: 1993Inhibition of the key enzyme thymidylate synthase (TS) is a major cause of the activity of 5-fluorouracil (5-FU) as a cancer chemotherapeutic agent...
- CYCLIC NUCLEOTIDES, CYCLOPHOSPHAMIDES, AND ANTIVIRALSWESLEY 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/..
- NOVEL TREATMENT OF REFRACTORY GI MALIGNANCIESScott 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...
- Tunneling and Dynamics in Enzyme Catalyzed ReactionsAmnon Kohen; Fiscal Year: 2012..A mechanistic investigation of C-H bond activation in alternative dihydrofolate reductases (DHFRs) and thymidylate synthase (TSase) will be conducted...
- EDITING OF THYMIDYLATE SYNTHASE RNABRUCE DOLNICK; Fiscal Year: 2002b>Thymidylate synthase is the enzyme responsible for the de novo synthesis of thymidylate and is a major target in chemotherapy...
- Molecular Correlates--Oxaliplatin/5FU/XRT, Esophageal CALakshmi 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 ..
- STRUCTURE BASED DRUG DESIGNRobert 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 ..
- CELLULAR PHARMACOLOGY OF THE STEREOISOMERS OF LEUCOVORINRichard 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 ..
- TUMOR MARKERS TO PREDICT TREATMENT RESPONSELynn 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. ..
- PET IMAGING OF DRUG KINETICS AND PATHWAYSAnthony Shields; Fiscal Year: 2002..an antimetabolite that is incorporated into DNA after sequential activation by thymidine kinase 1 (TK) and thymidylate synthase (TS)...
- Molecular Approach in Predicting 5-Fluorouracil EfficacyRobert 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...
- MOLECULAR AND ELECTRONIC STRUCTURES OF ANTIFOLATE DRUGSVivian Cody; Fiscal Year: 1991..biological mechanisms regulating folate-dependent enzymes, in particular dihydrofolate reductase (DHFR) and thymidylate synthase (TS)...
- QUORUM SENSING IN HUMAN CELLSBRUCE 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)...
- QUORUM SENSING IN HUMAN CELLSBRUCE 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)...
- NCI OUTSTANDING INVESTIGATORS GRANTFrank Maley; Fiscal Year: 2000Because 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...
- MOLECULAR PROGNOSTIC INDICATORS IN COLORECTAL CANCERLeonard 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...
- RTS AND ITS ROLE IN CHEMOTHERAPYBRUCE 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...
- PROTECTION OF HOST TISSUES FROM FDURD TOXICITYJonathan 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)...
- RELATION OF THYMIDYLATE SYNTHASE STRUCTURE TO FUNCTIONJAMES APPLEMAN; Fiscal Year: 1992b>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...
- THYMIDYLATE SYNTHASE GENE EXPRESSIONLee Johnson; Fiscal Year: 2002b>Thymidylate synthase (TS) is an essential enzyme in proliferating cells and an important target of chemotherapeutic drugs...
- MULTISUBSTRATE ENZYME INHIBITORSARTHUR BROOM; Fiscal Year: 1991The 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 ..
- FLUOROPYRIMIDINE RESPONSE MODULATION BY FOLINIC ACIDSONDRA 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...
- CRYSTALLOGRAPHIC STUDIES OF THYMIDYLATE SYNTHASEJanet Finer Moore; Fiscal Year: 2003The broad objectives of the work are to understand the functions of thymidylate synthase (TS) and other nucleotide, RNA and DNA-modifying enzymes...
- PROGRAMMED/NONPROGRAMMED CYTOX BY FLUOROPYRIMIDINESJonathan 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 ..
- ANTIMALARIAL ACTIVITY OF OROTIC ACID ANALOGSPRADIPSINH RATHOD; Fiscal Year: 1993..If successful in vitro, it will tell us that derivatives of dihydroorotate may also be highly effective antimalarial drugs...
- 5 FLUOROURACIL TARGET IN EUKARYOTIC CELLSDavid 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...
- The Yeast Exosome as a Model Anticancer Drug TargetJames 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. ..
- THE MECHANISM OF ACTION OF THYMIDYLATE SYNTHETASER Dunlap; Fiscal Year: 1980....
- A Molecular Approach For Opportunistic HIV-1 InfectionsKaren Anderson; Fiscal Year: 2007..Two enzymes crucial for DNA synthesis and one-carbon transfers are thymidylate synthase and dihydrofolate reductase...
- SYNTHESIS OF NOVEL THYMIDYLATE SYNTHASE INHIBITORSRobert Kempton; Fiscal Year: 1992..b>Thymidylate synthase (TS, EC 2.1.1...
- PROTEIN STRUCTURE-FUNCTION STUDIES USING UAG SUPPRESSORSJeffrey 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...
- Thymidylate Synthases: Modes of Catalysis and InhibitionLukasz Lebioda; Fiscal Year: 2009The 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...
- GENE INTERACTIONS IN COLON CANCERLeonard 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, ..
- Novel Single, Dual and Multitargeted Inhibitors of RTKsAleem Gangjee; Fiscal Year: 2007..abstract_text> ..
- MOLECULAR PROGNOSTIC INDICATORS IN ESOPHAGEAL CANCERPeter 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 ..
- CRYPTOSPORIDIUM DHFR AS A CHEMOTHERAPEUTIC TARGETRichard Nelson; Fiscal Year: 1999..are the parasite dihydropteroate synthase (DHPS) and, in protozoa, the bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS)...
- STRUCTURE BASED ANALOGS AS ANTIOPPORTUNISTIC AGENTSAleem 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). ..
- Third Generation Antiopportunistic AgentsAleem Gangjee; Fiscal Year: 2003..Screening against tuberculosis (NIAID) and tumor cells in culture (NCI) is also proposed. ..
- NOVEL NONINDUCIBLE THYMIDYLATE SYNTHASE INHIBITORSAleem Gangjee; Fiscal Year: 2004..Recent studies indicate that the clinically used TS inhibitors 5FU, 5FdR, AD1694, and LY23154 all induce thymidylate synthase (TS) synthesis...
- Alpha Folate Receptor Mediated GARFTase Inhibitors as Selective Antitumor AgentsAleem Gangjee; Fiscal Year: 2010....
- Single Agents with Designed Combination Chemotherapy PotentialAleem Gangjee; Fiscal Year: 2010..that each inhibit VEGFR-2 and PDGFR-$, (tumor angiogenic effects) and remarkably also inhibit human thymidylate synthase (hTS) (cytotoxic effects)...
- DRUG SYNERGY WITH ANTIFOLATE COMBINATIONSJohn 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 ..
- rTS Signaling Mimetics As Novel Cancer TherapeuticsJie 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...
- Antitumor Antimitotics That Reverse Tumor ResistanceAleem 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. ..
- Novel, P. jirovecii Specific Antipneumocystis AgentsAleem Gangjee; Fiscal Year: 2009..These agents could be used alone or in combination to treat PCP thus providing novel agents against a new target. ..
- MECHANISMS OF DTMP SYNTHASE AND DCMP HYDROXYMETHLYLASELARRY HARDY; Fiscal Year: 1993b>Thymidylate synthase (TS) is an essential enzyme for DNA synthesis and is a target for anticancer and antimicrobial drugs...
- APTAMER BASED BACTERIAL INHIBITION SYSTEMJonathan 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...
- DTMP SYNTHASE: NMR AND MECHANISTIC STUDIESR 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 ..
- THYMIDYLATE SYNTHASE INHIBITORS IN HEAD AND NECK CANCERYoucef 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. ..
- NON INVASIVE MEASUREMENT OF THYMIDYLATE SYNTHASE INHIBITPatricia Price; Fiscal Year: 2001DESCRIPTION: (Applicant's Description) Thymidylate synthase (TS) is the target of several anticancer agents due its important role in the de novo synthesis of DNA...
- Prognostic Markers in Trials for Head and Neck CancerKevin Cullen; Fiscal Year: 2005Our 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 ..
- SITE-DIRECTED DRUG DISCOVERYJames 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 ..
- PROGNOSTIC INDICATORS IN LOCALIZED COLON CANCERHEINZ 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 ..