PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 2007575-0 1991 Decreased folylpolyglutamate synthetase activity as a mechanism of methotrexate resistance in CCRF-CEM human leukemia sublines. Methotrexate 67-79 folylpolyglutamate synthase Homo sapiens 10-39 2007575-8 1991 Decreased polyglutamylation was attributable to folylpolyglutamate synthetase (FPGS) activity in R30dm extracts which was 1, 2, and less than or equal to 10% of CCRF-CEM extracts with the substrates MTX, aminopterin, and naturally occurring folates, respectively. Methotrexate 199-202 folylpolyglutamate synthase Homo sapiens 48-77 2007575-8 1991 Decreased polyglutamylation was attributable to folylpolyglutamate synthetase (FPGS) activity in R30dm extracts which was 1, 2, and less than or equal to 10% of CCRF-CEM extracts with the substrates MTX, aminopterin, and naturally occurring folates, respectively. Methotrexate 199-202 folylpolyglutamate synthase Homo sapiens 79-83 2007575-9 1991 Comparison of cell lines with varying levels of resistance to short term MTX exposure indicated that the extent of MTX resistance was proportional to the reduction of FPGS activity. Methotrexate 73-76 folylpolyglutamate synthase Homo sapiens 167-171 2007575-9 1991 Comparison of cell lines with varying levels of resistance to short term MTX exposure indicated that the extent of MTX resistance was proportional to the reduction of FPGS activity. Methotrexate 115-118 folylpolyglutamate synthase Homo sapiens 167-171 2007575-10 1991 The evidence supported decreased FPGS activity as the mechanism of resistance to short MTX exposure in the cell lines investigated. Methotrexate 87-90 folylpolyglutamate synthase Homo sapiens 33-37 3190739-4 1988 It was a much more potent linear competitive inhibitor of human FPGS than the corresponding methotrexate derivative previously described (Ki = 0.15-0.26 and 3 microM respectively). Methotrexate 92-104 folylpolyglutamate synthase Homo sapiens 64-68 2168155-8 1990 The relative distribution of products synthesized from methotrexate or tetrahydrofolate by FPGS was not altered by addition of NaHCO3. Methotrexate 55-67 folylpolyglutamate synthase Homo sapiens 91-95 3840051-1 1985 The glutamylation of methotrexate catalyzed by beef liver folypolyglutamate synthetase (FPGS) is activated by addition of pteroic acid. Methotrexate 21-33 folylpolyglutamate synthase Homo sapiens 88-92 2906805-2 1988 COOH-18O-labeled folate, methotrexate, and dihydropteroate, in addition to [17O]-glutamate, were synthesized and used as substrates for folylpolyglutamate synthetase (FPGS) isolated from Escherichia coli, hog liver, and rat liver and for dihydrofolate synthetase (DHFS) isolated from E. coli. Methotrexate 25-37 folylpolyglutamate synthase Homo sapiens 167-171 3431589-0 1987 Synthesis and biologic activity of new side-chain-altered methotrexate and aminopterin analogs with dual inhibitory action against dihydrofolate reductase and folylpolyglutamate synthetase. Methotrexate 58-70 folylpolyglutamate synthase Homo sapiens 159-188 3619447-11 1987 Comparison of MTX with its higher polyglutamates (MTX-Glu2 to MTX-Glu6) as FPGS substrates indicated a significant decrease in Vmax values with increasing glutamate chain length which was partially compensated for by a corresponding decrease in Km. Methotrexate 14-17 folylpolyglutamate synthase Homo sapiens 75-79 2448652-1 1987 Folate monoglutamates and classical antifols such as methotrexate (MTX) are converted intracellularly to poly-gamma-glutamyl forms by folylpolyglutamate synthetase (FPGS). Methotrexate 53-65 folylpolyglutamate synthase Homo sapiens 134-163 2448652-1 1987 Folate monoglutamates and classical antifols such as methotrexate (MTX) are converted intracellularly to poly-gamma-glutamyl forms by folylpolyglutamate synthetase (FPGS). Methotrexate 53-65 folylpolyglutamate synthase Homo sapiens 165-169 2448652-1 1987 Folate monoglutamates and classical antifols such as methotrexate (MTX) are converted intracellularly to poly-gamma-glutamyl forms by folylpolyglutamate synthetase (FPGS). Methotrexate 67-70 folylpolyglutamate synthase Homo sapiens 134-163 2448652-1 1987 Folate monoglutamates and classical antifols such as methotrexate (MTX) are converted intracellularly to poly-gamma-glutamyl forms by folylpolyglutamate synthetase (FPGS). Methotrexate 67-70 folylpolyglutamate synthase Homo sapiens 165-169 3431589-1 1987 Replacement of the glutamic acid (Glu) moiety in methotrexate (MTX) and aminopterin (AMT) by 2-amino-4-phosphonobutyric acid (APBA) and ornithine (Orn) has been found to give analogs that retain the ability to inhibit dihydrofolate reductase (DHFR) while also displaying high activity against folylpolyglutamate synthetase (FPGS). Methotrexate 63-66 folylpolyglutamate synthase Homo sapiens 293-322 3431589-1 1987 Replacement of the glutamic acid (Glu) moiety in methotrexate (MTX) and aminopterin (AMT) by 2-amino-4-phosphonobutyric acid (APBA) and ornithine (Orn) has been found to give analogs that retain the ability to inhibit dihydrofolate reductase (DHFR) while also displaying high activity against folylpolyglutamate synthetase (FPGS). Methotrexate 63-66 folylpolyglutamate synthase Homo sapiens 324-328 3873989-1 1985 The antifolate drugs methotrexate (MTX) and aminopterin (AM) have been tested as substrates for folylpolyglutamate synthetase (FPGS) partially purified from beef liver. Methotrexate 21-33 folylpolyglutamate synthase Homo sapiens 96-125 3756000-7 1986 5-Formyltetrahydrofolate, which is used as a rescue agent in high-dose methotrexate-rescue chemotherapy, is a better alternate substrate of FPGS than is methotrexate and therefore is a potent competitive inhibitor of the glutamylation of methotrexate. Methotrexate 71-83 folylpolyglutamate synthase Homo sapiens 140-144 3873989-1 1985 The antifolate drugs methotrexate (MTX) and aminopterin (AM) have been tested as substrates for folylpolyglutamate synthetase (FPGS) partially purified from beef liver. Methotrexate 21-33 folylpolyglutamate synthase Homo sapiens 127-131 3873989-1 1985 The antifolate drugs methotrexate (MTX) and aminopterin (AM) have been tested as substrates for folylpolyglutamate synthetase (FPGS) partially purified from beef liver. Methotrexate 35-38 folylpolyglutamate synthase Homo sapiens 96-125 3873989-1 1985 The antifolate drugs methotrexate (MTX) and aminopterin (AM) have been tested as substrates for folylpolyglutamate synthetase (FPGS) partially purified from beef liver. Methotrexate 35-38 folylpolyglutamate synthase Homo sapiens 127-131 3873989-4 1985 Based on their ratios of Vmax to Km, AM is a better substrate than is MTX for the beef liver FPGS. Methotrexate 70-73 folylpolyglutamate synthase Homo sapiens 93-97 3873989-6 1985 The 7-hydroxy metabolites of MTX and AM also are substrates for FPGS. Methotrexate 29-32 folylpolyglutamate synthase Homo sapiens 64-68 3873989-8 1985 Folinic acid, often used as the rescue agent in high-dose MTX therapy, has a low Km with mammalian FPGS (7 microM). Methotrexate 58-61 folylpolyglutamate synthase Homo sapiens 99-103 3873989-11 1985 This inhibition is competitive, presumably because folinic acid and MTX are competing substrates for FPGS. Methotrexate 68-71 folylpolyglutamate synthase Homo sapiens 101-105 3873989-18 1985 Our observations using MTX and AM with the enzymatic FPGS system help to rationalize the therapeutic use of antifolates. Methotrexate 23-26 folylpolyglutamate synthase Homo sapiens 53-57 6577780-4 1983 Folylpolyglutamate synthetase, partially purified from mouse liver, was found to accept a variety of folate derivatives as substrates, including pteroic acid and methotrexate; however, the concentration of these substrates that saturated the reaction varied considerably. Methotrexate 162-174 folylpolyglutamate synthase Homo sapiens 0-29 32694622-3 2020 Applying whole-exome sequencing to eight triplicate samples, we identified in one patient relapse-specific mutations in the folylpolyglutamate synthetase (FPGS) gene, whose product catalyzes the addition of multiple glutamate residues (polyglutamation) to methotrexate upon their entry into the cells. Methotrexate 256-268 folylpolyglutamate synthase Homo sapiens 124-153 32391884-0 2020 Effects of germline variants in DHFR and FPGS on methotrexate metabolism and relapse of leukemia. Methotrexate 49-61 folylpolyglutamate synthase Homo sapiens 41-45 32391884-3 2020 The intergenic SNP rs1382539 located in a regulatory element of DHFR was associated with increased levels of short-chain MTX polyglutamates (P = 1.1 x 10-8) due to suppression of enhancer activity, while rs35789560 in FPGS (p.R466C, P = 5.6 x 10-9) was associated with decreased levels of long-chain MTX polyglutamates through reduced catalytic activity. Methotrexate 121-124 folylpolyglutamate synthase Homo sapiens 218-222 32940699-0 2021 Association of altered folylpolyglutamate synthetase pre-mRNA splicing with methotrexate unresponsiveness in early rheumatoid arthritis. Methotrexate 76-88 folylpolyglutamate synthase Homo sapiens 23-52 33564926-8 2021 Moreover, our team has already developed two LC-MS/MS-based methods to respectively quantify methotrexate in plasma samples and two key proteins (gamma-glutamyl hydrolase [GGH] and folylpolyglutamate synthetase [FPGS]) in peripheral blood mononuclear cells (PBMC). Methotrexate 93-105 folylpolyglutamate synthase Homo sapiens 212-216 32694622-3 2020 Applying whole-exome sequencing to eight triplicate samples, we identified in one patient relapse-specific mutations in the folylpolyglutamate synthetase (FPGS) gene, whose product catalyzes the addition of multiple glutamate residues (polyglutamation) to methotrexate upon their entry into the cells. Methotrexate 256-268 folylpolyglutamate synthase Homo sapiens 155-159 32694622-8 2020 Functional characterization of the FPGS mutants showed that they directly resulted in decreased enzymatic activity, leading to significant reduction in methotrexate polyglutamation, and therefore likely contributed to drug resistance and relapse in these cases. Methotrexate 152-164 folylpolyglutamate synthase Homo sapiens 35-39 32587478-0 2020 beta-catenin promotes MTX resistance of leukemia cells by down-regulating FPGS expression via NF-kappaB. Methotrexate 22-25 folylpolyglutamate synthase Homo sapiens 74-78 32793886-9 2020 Results: HDACIs upregulated the ratio of FPGS/GGH expression resulting in increased polyglutamylation of MTX, but also downregulated expression of the target molecule of MTX: DHFR. Methotrexate 105-108 folylpolyglutamate synthase Homo sapiens 41-45 32587478-2 2020 In the present study, we demonstrate a critical role of beta-catenin-NF-kappaB-FPGS pathway in MTX resistance in the human T-lineage ALL cell lines. Methotrexate 95-98 folylpolyglutamate synthase Homo sapiens 79-83 32587478-10 2020 Conclusions: Taken together, our results demonstrate that beta-catenin may contribute to MTX resistance in leukemia cells via the beta-catenin-NF-kappaB-FPGS pathway, posing beta-catenin as a potential target for combination treatments during ALL therapy. Methotrexate 89-92 folylpolyglutamate synthase Homo sapiens 153-157 31522319-12 2020 A model including both BMI and FPGS rs10106 could modestly predict methotrexate intolerance with an accuracy of 66.3%. Methotrexate 67-79 folylpolyglutamate synthase Homo sapiens 31-35 32256983-6 2020 METHODS: This review discusses the effects of FPGS and GGH on chemosensitivity to cancer chemotherapeutic agents such as antifolates, such as methotrexate, and 5-fluorouracil. Methotrexate 142-154 folylpolyglutamate synthase Homo sapiens 46-50 32256983-10 2020 Generally, high FPGS and/or low GGH activity is associated with increased chemosensitivity of cancer cells to methotrexate and 5-fluorouracil, while low FPGS and/or high GGH activity seems to correspond to resistance to these drugs. Methotrexate 110-122 folylpolyglutamate synthase Homo sapiens 16-20 31522319-13 2020 CONCLUSIONS: A clinical-genetic model including BMI and SNP FPGS 10101 was found to have a modest prediction ability for methotrexate intolerance. Methotrexate 121-133 folylpolyglutamate synthase Homo sapiens 60-64 31522319-15 2020 SNP FPGS rs10106 and low body mass index were associated with methotrexate intolerance. Methotrexate 62-74 folylpolyglutamate synthase Homo sapiens 4-8 29475458-11 2018 In vitro, the relief effect of LV after MTX administration was significantly enhanced after FPGS knockdown in al cell lines, whereas enhancement of FPGS expression by NaBu treatment significantly reduced this relief effect. Methotrexate 40-43 folylpolyglutamate synthase Homo sapiens 92-96 31779260-4 2019 Once inside leukemic cells, MTX is metabolized into methotrexate polyglutamates (MTX-PG) by action of the enzyme folylpolyglutamate synthetase (FPGS), leading to a longer action compared to that of MTX alone. Methotrexate 28-31 folylpolyglutamate synthase Homo sapiens 144-148 31779260-4 2019 Once inside leukemic cells, MTX is metabolized into methotrexate polyglutamates (MTX-PG) by action of the enzyme folylpolyglutamate synthetase (FPGS), leading to a longer action compared to that of MTX alone. Methotrexate 81-84 folylpolyglutamate synthase Homo sapiens 144-148 31779260-4 2019 Once inside leukemic cells, MTX is metabolized into methotrexate polyglutamates (MTX-PG) by action of the enzyme folylpolyglutamate synthetase (FPGS), leading to a longer action compared to that of MTX alone. Methotrexate 81-84 folylpolyglutamate synthase Homo sapiens 144-148 31008996-1 2019 BACKGROUND: Folylpolyglutamate synthetase (FPGS) is a crucial enzyme in both cellular folate homeostasis and the intracellular retention of folate analogue drugs like methotrexate (MTX), which is commonly used for the treatment of (pediatric) leukemia and the anchor drug in rheumatoid arthritis (RA) treatment. Methotrexate 167-179 folylpolyglutamate synthase Homo sapiens 12-41 31008996-1 2019 BACKGROUND: Folylpolyglutamate synthetase (FPGS) is a crucial enzyme in both cellular folate homeostasis and the intracellular retention of folate analogue drugs like methotrexate (MTX), which is commonly used for the treatment of (pediatric) leukemia and the anchor drug in rheumatoid arthritis (RA) treatment. Methotrexate 167-179 folylpolyglutamate synthase Homo sapiens 43-47 31008996-1 2019 BACKGROUND: Folylpolyglutamate synthetase (FPGS) is a crucial enzyme in both cellular folate homeostasis and the intracellular retention of folate analogue drugs like methotrexate (MTX), which is commonly used for the treatment of (pediatric) leukemia and the anchor drug in rheumatoid arthritis (RA) treatment. Methotrexate 181-184 folylpolyglutamate synthase Homo sapiens 12-41 31008996-1 2019 BACKGROUND: Folylpolyglutamate synthetase (FPGS) is a crucial enzyme in both cellular folate homeostasis and the intracellular retention of folate analogue drugs like methotrexate (MTX), which is commonly used for the treatment of (pediatric) leukemia and the anchor drug in rheumatoid arthritis (RA) treatment. Methotrexate 181-184 folylpolyglutamate synthase Homo sapiens 43-47 31008996-8 2019 Moreover, the UHPLC-MS/MS method also allowed evaluation of FPGS enzyme kinetic parameters revealing Km values for the substrates MTX and L-glutamic acid of 64 micromol/L and 2.2 mmol/L, respectively. Methotrexate 130-133 folylpolyglutamate synthase Homo sapiens 60-64 31008996-10 2019 CONCLUSIONS: Collectively, given its sensitivity with low cell numbers and avoidance of radioactive substrates, UHPLC-MS/MS-based analysis of FPGS activity may be eligible for routine therapeutic drug monitoring of MTX in RA and leukemia for therapy (non)response evaluations. Methotrexate 215-218 folylpolyglutamate synthase Homo sapiens 142-146 30851225-4 2019 Mechanistically, SKA1 overexpression lead to a downregulation of folylpoly-gamma-glutamate synthetase (FPGS), a key enzyme that converts MTX into its active form, MTX-PG. Methotrexate 137-140 folylpolyglutamate synthase Homo sapiens 65-101 30851225-4 2019 Mechanistically, SKA1 overexpression lead to a downregulation of folylpoly-gamma-glutamate synthetase (FPGS), a key enzyme that converts MTX into its active form, MTX-PG. Methotrexate 137-140 folylpolyglutamate synthase Homo sapiens 103-107 30851225-6 2019 ChIP analysis revealed that RPB3 binds the promoter region of the FPGS gene and triggers FPGS transcription upon MTX treatment in SW1353, a MTX-sensitive OS cell line lacking endogenous SKA1 expression. Methotrexate 113-116 folylpolyglutamate synthase Homo sapiens 89-93 30851225-9 2019 Collectively, our study has established the de novo MTX-resistant cell line SF-86 and identified SKA1 as a novel regulator of FPGS, playing a key role in the development of de novo MTX-resistance in OS. Methotrexate 181-184 folylpolyglutamate synthase Homo sapiens 126-130 24168269-1 2013 BACKGROUND: Folypolyglutamate synthase (FPGS) catalyzes the polyglutamation of folates and antifolates, such as methotrexate (MTX), to produce highly active metabolites. Methotrexate 112-124 folylpolyglutamate synthase Homo sapiens 12-38 28598776-5 2017 Expression of genes important to the transport (SLC19A1, ABCB1, ABCC1, ABCG2), metabolism (FPGS, GGH), and mechanism of action (TYMS, MTR, MTRR) of MTX, including for the adenosine receptors ADORA1, ADORA2A, ADORA2B, ADORA3 and ADORA3variant were quantitated by real-time PCR in each nodule sample. Methotrexate 148-151 folylpolyglutamate synthase Homo sapiens 91-95 29095107-1 2017 AIM: To investigate the impact of polymorphisms in the FPGS, GGH and SLCO1B1 genes on high dose methotrexate (HD-MTX) related toxicity in Chinese patients with non-Hodgkin lymphoma (NHL). Methotrexate 96-108 folylpolyglutamate synthase Homo sapiens 55-59 27987364-0 2016 Effect of the Polymorphism of Folylpolyglutamate Synthetase on Treatment of High-Dose Methotrexate in Pediatric Patients with Acute Lymphocytic Leukemia. Methotrexate 86-98 folylpolyglutamate synthase Homo sapiens 30-59 27987364-1 2016 BACKGROUND The aim of this study was to investigate the association of the polymorphism of folylpolyglutamate synthetase (FPGS) with the dynamic plasma concentration of methotrexate (MTX) in pediatric patients with acute lymphocytic leukemia (ALL), as well as the prognosis. Methotrexate 169-181 folylpolyglutamate synthase Homo sapiens 91-120 27987364-1 2016 BACKGROUND The aim of this study was to investigate the association of the polymorphism of folylpolyglutamate synthetase (FPGS) with the dynamic plasma concentration of methotrexate (MTX) in pediatric patients with acute lymphocytic leukemia (ALL), as well as the prognosis. Methotrexate 169-181 folylpolyglutamate synthase Homo sapiens 122-126 27987364-1 2016 BACKGROUND The aim of this study was to investigate the association of the polymorphism of folylpolyglutamate synthetase (FPGS) with the dynamic plasma concentration of methotrexate (MTX) in pediatric patients with acute lymphocytic leukemia (ALL), as well as the prognosis. Methotrexate 183-186 folylpolyglutamate synthase Homo sapiens 91-120 27987364-1 2016 BACKGROUND The aim of this study was to investigate the association of the polymorphism of folylpolyglutamate synthetase (FPGS) with the dynamic plasma concentration of methotrexate (MTX) in pediatric patients with acute lymphocytic leukemia (ALL), as well as the prognosis. Methotrexate 183-186 folylpolyglutamate synthase Homo sapiens 122-126 27987364-7 2016 CONCLUSIONS Polymorphism of FPGS rs1544105 might be used as an effective approach for prediction of the treatment outcome of MTX. Methotrexate 125-128 folylpolyglutamate synthase Homo sapiens 28-32 26547381-0 2016 Folylpolyglutamate synthetase splicing alterations in acute lymphoblastic leukemia are provoked by methotrexate and other chemotherapeutics and mediate chemoresistance. Methotrexate 99-111 folylpolyglutamate synthase Homo sapiens 0-29 26547381-3 2016 We have recently shown that impaired folylpolyglutamate synthetase (FPGS) splicing possibly contributes to the loss of FPGS activity in MTX-resistant leukemia cell line models and adult leukemia patients. Methotrexate 136-139 folylpolyglutamate synthase Homo sapiens 68-72 26547381-3 2016 We have recently shown that impaired folylpolyglutamate synthetase (FPGS) splicing possibly contributes to the loss of FPGS activity in MTX-resistant leukemia cell line models and adult leukemia patients. Methotrexate 136-139 folylpolyglutamate synthase Homo sapiens 119-123 26652611-6 2016 The FPGS rs10106 variant was also associated with MTX survival (p = 0.005) and toxicity (p = 0.021). Methotrexate 50-53 folylpolyglutamate synthase Homo sapiens 4-8 26652611-8 2016 CONCLUSION: FPGS and ABCB1 genetic variants can influence the outcome in RA patients receiving MTX monotherapy. Methotrexate 95-98 folylpolyglutamate synthase Homo sapiens 12-16 24908438-0 2014 Influence of genetic polymorphisms of FPGS, GGH, and MTHFR on serum methotrexate levels in Chinese children with acute lymphoblastic leukemia. Methotrexate 68-80 folylpolyglutamate synthase Homo sapiens 38-42 24908438-10 2014 CONCLUSIONS: These data indicate that FPGS rs1544105, GGH rs3758149, and MTHFR rs1801133 polymorphisms contribute to the variability of MTX pharmacokinetics, and their genotyping may be useful to reduce toxicities associated with MTX therapy. Methotrexate 136-139 folylpolyglutamate synthase Homo sapiens 38-42 25013492-1 2014 Folylpolyglutamate synthase (FPGS) is the key enzyme that converts the chemotherapeutic agent, methotrexate (MTX), into MTX polyglutamate. Methotrexate 95-107 folylpolyglutamate synthase Homo sapiens 0-27 25013492-1 2014 Folylpolyglutamate synthase (FPGS) is the key enzyme that converts the chemotherapeutic agent, methotrexate (MTX), into MTX polyglutamate. Methotrexate 95-107 folylpolyglutamate synthase Homo sapiens 29-33 25013492-1 2014 Folylpolyglutamate synthase (FPGS) is the key enzyme that converts the chemotherapeutic agent, methotrexate (MTX), into MTX polyglutamate. Methotrexate 109-112 folylpolyglutamate synthase Homo sapiens 0-27 25013492-1 2014 Folylpolyglutamate synthase (FPGS) is the key enzyme that converts the chemotherapeutic agent, methotrexate (MTX), into MTX polyglutamate. Methotrexate 109-112 folylpolyglutamate synthase Homo sapiens 29-33 27980801-4 2016 The purpose of this study was to investigate the allelic frequencies in different ethnic and/or population groups in the 10 polymorphisms of enzyme proteins and transporters related to the MTX response and pharmacokinetics including MTHFR, TYMS, RFC1, FPGS, GGH, ABCB1, ABCC2 and ABCG2 in unrelated healthy Japanese adults and patients with RA. Methotrexate 189-192 folylpolyglutamate synthase Homo sapiens 252-256 27146084-2 2016 Reduced folate carrier-1 (RFC-1), folypolyformyl glutamate synthase (FPGS), and gamma-glutamyl hydrolase (GGH) are important transporters and enzymes that convert methotrexate (MTX) in the body. Methotrexate 163-175 folylpolyglutamate synthase Homo sapiens 34-67 27146084-2 2016 Reduced folate carrier-1 (RFC-1), folypolyformyl glutamate synthase (FPGS), and gamma-glutamyl hydrolase (GGH) are important transporters and enzymes that convert methotrexate (MTX) in the body. Methotrexate 163-175 folylpolyglutamate synthase Homo sapiens 69-73 27146084-2 2016 Reduced folate carrier-1 (RFC-1), folypolyformyl glutamate synthase (FPGS), and gamma-glutamyl hydrolase (GGH) are important transporters and enzymes that convert methotrexate (MTX) in the body. Methotrexate 177-180 folylpolyglutamate synthase Homo sapiens 34-67 27146084-2 2016 Reduced folate carrier-1 (RFC-1), folypolyformyl glutamate synthase (FPGS), and gamma-glutamyl hydrolase (GGH) are important transporters and enzymes that convert methotrexate (MTX) in the body. Methotrexate 177-180 folylpolyglutamate synthase Homo sapiens 69-73 25225283-11 2014 Patients with the folylpolyglutamate synthase (FPGS) rs4451422 wild-type genotype had higher concentrations of MTX-PG3 (p<0.05), MTX-PG4+5 (p<0.05), and total MTX-PG (p<0.05) in both cohorts. Methotrexate 111-114 folylpolyglutamate synthase Homo sapiens 18-45 25225283-11 2014 Patients with the folylpolyglutamate synthase (FPGS) rs4451422 wild-type genotype had higher concentrations of MTX-PG3 (p<0.05), MTX-PG4+5 (p<0.05), and total MTX-PG (p<0.05) in both cohorts. Methotrexate 111-114 folylpolyglutamate synthase Homo sapiens 47-51 24762994-0 2014 [Correlation analysis of FPGS rs10760502G>a polymorphism with prognosis and MTX-related toxicity in pediatric B-cell acute lymphoblastic leukemia]. Methotrexate 79-82 folylpolyglutamate synthase Homo sapiens 25-29 24762994-1 2014 This study was aimed to explore the relation between folylpolyglutamate synthetase (FPGS) rs10760502 polymorphism and prognosis and methotrexate (MTX)-related toxicities in pediatric B-cell acute lymphoblastic leukemia (B-ALL). Methotrexate 132-144 folylpolyglutamate synthase Homo sapiens 84-88 24762994-1 2014 This study was aimed to explore the relation between folylpolyglutamate synthetase (FPGS) rs10760502 polymorphism and prognosis and methotrexate (MTX)-related toxicities in pediatric B-cell acute lymphoblastic leukemia (B-ALL). Methotrexate 146-149 folylpolyglutamate synthase Homo sapiens 84-88 24168269-1 2013 BACKGROUND: Folypolyglutamate synthase (FPGS) catalyzes the polyglutamation of folates and antifolates, such as methotrexate (MTX), to produce highly active metabolites. Methotrexate 112-124 folylpolyglutamate synthase Homo sapiens 40-44 24168269-1 2013 BACKGROUND: Folypolyglutamate synthase (FPGS) catalyzes the polyglutamation of folates and antifolates, such as methotrexate (MTX), to produce highly active metabolites. Methotrexate 126-129 folylpolyglutamate synthase Homo sapiens 12-38 24168269-1 2013 BACKGROUND: Folypolyglutamate synthase (FPGS) catalyzes the polyglutamation of folates and antifolates, such as methotrexate (MTX), to produce highly active metabolites. Methotrexate 126-129 folylpolyglutamate synthase Homo sapiens 40-44 21418912-0 2011 [Differential gene expression of folylpolyglutamate synthetase in cytoplasm and mitochondria in acquired methotrexate enantiomers resistant to lung cancer A549 cell lines]. Methotrexate 105-117 folylpolyglutamate synthase Homo sapiens 33-62 22698741-1 2012 Folylpolyglutamate synthetase (FPGS) is the key enzyme that converts chemotherapy drug Methotrexate (MTX) into MTXPG. Methotrexate 101-104 folylpolyglutamate synthase Homo sapiens 31-35 22698741-2 2012 The expression level of FPGS directly influences MTX-sensitivity of tumor cells. Methotrexate 49-52 folylpolyglutamate synthase Homo sapiens 24-28 22698741-3 2012 Compared with B-cell acute lymphocytic leukemia (B-ALL), T-cell acute lymphocytic leukemia (T-ALL) cells express a lower level of FPGS, which results in insensitivity of the cells to MTX. Methotrexate 183-186 folylpolyglutamate synthase Homo sapiens 130-134 22698741-5 2012 In this study, FPGS expression plasmid containing mbr element at the 5" upstream of the gene was constructed and transfected into Jurkat cells to sensitize the cells to MTX. Methotrexate 169-172 folylpolyglutamate synthase Homo sapiens 15-19 22698741-6 2012 Western blotting and MTT assay were applied to detect the FPGS expression level and suppression rate of the cells treated by MTX, respectively. Methotrexate 125-128 folylpolyglutamate synthase Homo sapiens 58-62 22698741-7 2012 We found that the mbr enhanced the expression of FPGS significantly and increased sensitivity of Jurkat cells to MTX efficiently, while FPGS expression plasmid without mbr element had less effect. Methotrexate 113-116 folylpolyglutamate synthase Homo sapiens 49-53 23949282-0 2013 Targeted expression of human folylpolyglutamate synthase for selective enhancement of methotrexate chemotherapy in osteosarcoma cells. Methotrexate 86-98 folylpolyglutamate synthase Homo sapiens 29-56 23949282-4 2013 In the present study, we proved the hypothesis that transfer of the human fpgs gene into osteosarcoma cells may augment their MTX sensitivity. Methotrexate 126-129 folylpolyglutamate synthase Homo sapiens 74-78 23858048-5 2013 Expression of SLC19A1, GGH, FPGS, ABCC1, and MTRR was significantly higher in patients receiving MTX compared to those not receiving MTX (p < 0.05). Methotrexate 97-100 folylpolyglutamate synthase Homo sapiens 28-32 22698741-0 2012 [The mbr-FPGS efficient expression plasmid enhances the sensitivity of Jurkat cells to methotrexate]. Methotrexate 87-99 folylpolyglutamate synthase Homo sapiens 9-13 22698741-1 2012 Folylpolyglutamate synthetase (FPGS) is the key enzyme that converts chemotherapy drug Methotrexate (MTX) into MTXPG. Methotrexate 87-99 folylpolyglutamate synthase Homo sapiens 0-29 22698741-1 2012 Folylpolyglutamate synthetase (FPGS) is the key enzyme that converts chemotherapy drug Methotrexate (MTX) into MTXPG. Methotrexate 87-99 folylpolyglutamate synthase Homo sapiens 31-35 22698741-1 2012 Folylpolyglutamate synthetase (FPGS) is the key enzyme that converts chemotherapy drug Methotrexate (MTX) into MTXPG. Methotrexate 101-104 folylpolyglutamate synthase Homo sapiens 0-29 21418912-1 2011 OBJECTIVE: To investigate the relationship between the resistance of methotrexate (MTX) enantiomer and the gene expression levels of folylpolyglutamate synthetase (FPGS). Methotrexate 69-81 folylpolyglutamate synthase Homo sapiens 133-162 21418912-1 2011 OBJECTIVE: To investigate the relationship between the resistance of methotrexate (MTX) enantiomer and the gene expression levels of folylpolyglutamate synthetase (FPGS). Methotrexate 69-81 folylpolyglutamate synthase Homo sapiens 164-168 21418912-1 2011 OBJECTIVE: To investigate the relationship between the resistance of methotrexate (MTX) enantiomer and the gene expression levels of folylpolyglutamate synthetase (FPGS). Methotrexate 83-86 folylpolyglutamate synthase Homo sapiens 133-162 21418912-1 2011 OBJECTIVE: To investigate the relationship between the resistance of methotrexate (MTX) enantiomer and the gene expression levels of folylpolyglutamate synthetase (FPGS). Methotrexate 83-86 folylpolyglutamate synthase Homo sapiens 164-168 21219404-2 2011 METHODS: Eight gene polymorphisms within the MTX pathway genes, namely, RFC, BCRP, MTHFR (two), FPGS, gamma-glutamyl hydrolase (GGH; two) and ATIC, were genotyped using TaqMan assays. Methotrexate 45-48 folylpolyglutamate synthase Homo sapiens 96-100 19902562-7 2009 On regression analyses, FPGS rs1544105, TYMS rs2853539, DHFR rs7387, and ADA rs244076 were identified as putative predictors for MTX response. Methotrexate 129-132 folylpolyglutamate synthase Homo sapiens 24-28 20072153-2 2010 The antifolate methotrexate (MTX), a universal component of ALL therapies, is metabolized by folylpoly-gamma-glutamate synthetase (FPGS) into long-chain polyglutamates (MTX-PG(3-7)), resulting in enhanced cytotoxicity from prolonged inhibition of dihydrofolate reductase (DHFR) and thymidylate synthetase (TS). Methotrexate 15-27 folylpolyglutamate synthase Homo sapiens 93-129 20072153-2 2010 The antifolate methotrexate (MTX), a universal component of ALL therapies, is metabolized by folylpoly-gamma-glutamate synthetase (FPGS) into long-chain polyglutamates (MTX-PG(3-7)), resulting in enhanced cytotoxicity from prolonged inhibition of dihydrofolate reductase (DHFR) and thymidylate synthetase (TS). Methotrexate 15-27 folylpolyglutamate synthase Homo sapiens 131-135 20072153-2 2010 The antifolate methotrexate (MTX), a universal component of ALL therapies, is metabolized by folylpoly-gamma-glutamate synthetase (FPGS) into long-chain polyglutamates (MTX-PG(3-7)), resulting in enhanced cytotoxicity from prolonged inhibition of dihydrofolate reductase (DHFR) and thymidylate synthetase (TS). Methotrexate 29-32 folylpolyglutamate synthase Homo sapiens 93-129 20072153-2 2010 The antifolate methotrexate (MTX), a universal component of ALL therapies, is metabolized by folylpoly-gamma-glutamate synthetase (FPGS) into long-chain polyglutamates (MTX-PG(3-7)), resulting in enhanced cytotoxicity from prolonged inhibition of dihydrofolate reductase (DHFR) and thymidylate synthetase (TS). Methotrexate 29-32 folylpolyglutamate synthase Homo sapiens 131-135 18672898-1 2008 Folylpoly-gamma-glutamate synthetase (FPGS, EC 6.3.2.17) is an ATP-dependent ligase that catalyzes formation of poly-gamma-glutamate derivatives of reduced folates and antifolates such as methotrexate and 5,10-dideaza-5,6,7,8-tetrahydrofolate (DDAH 4PteGlu 1). Methotrexate 188-200 folylpolyglutamate synthase Homo sapiens 0-36 19131550-1 2009 Folylpoly-gamma-gluatamate synthetase (FPGS) catalyzes the polyglutamylation and thus intracellular retention of folates and antifolates (eg, methotrexate; MTX) through the addition of multiple glutamate equivalents to their gamma-carboxyl residue. Methotrexate 142-154 folylpolyglutamate synthase Homo sapiens 0-37 19131550-1 2009 Folylpoly-gamma-gluatamate synthetase (FPGS) catalyzes the polyglutamylation and thus intracellular retention of folates and antifolates (eg, methotrexate; MTX) through the addition of multiple glutamate equivalents to their gamma-carboxyl residue. Methotrexate 142-154 folylpolyglutamate synthase Homo sapiens 39-43 19426680-1 2009 In vitro treatment of human T-cell leukemia cells with 7-hydroxymethotrexate, the major metabolite of methotrexate resulted in acquired resistance as a result of the complete loss of folypolyglutamate synthetase (FPGS) activity. Methotrexate 64-76 folylpolyglutamate synthase Homo sapiens 213-217 18672898-1 2008 Folylpoly-gamma-glutamate synthetase (FPGS, EC 6.3.2.17) is an ATP-dependent ligase that catalyzes formation of poly-gamma-glutamate derivatives of reduced folates and antifolates such as methotrexate and 5,10-dideaza-5,6,7,8-tetrahydrofolate (DDAH 4PteGlu 1). Methotrexate 188-200 folylpolyglutamate synthase Homo sapiens 38-42 18025275-5 2007 We generated an in vitro model of FPGS overexpression and inhibition in breast cancer cells by stably transfecting human MDA-MB-435 breast cancer cells with the sense FPGS cDNA or FPGS-targeted small interfering RNA, respectively, and investigated the effects of FPGS modulation on chemosensitivity to 5FU and methotrexate. Methotrexate 310-322 folylpolyglutamate synthase Homo sapiens 34-38 18025275-3 2007 FPGS modulation affects the chemosensitivity of cancer cells to antifolates, such as methotrexate, and 5-fluorouracil (5FU) by altering polyglutamylation of antifolates and specific target intracellular folate cofactors. Methotrexate 85-97 folylpolyglutamate synthase Homo sapiens 0-4 18025275-7 2007 However, the effects of FPGS modulation on the chemosensitivity of breast cancer cells to 5FU and methotrexate seem to be highly complex and depend not only on polyglutamylation of a specific target intracellular folate cofactor or methotrexate, respectively, but also on total intracellular folate pools and polyglutamylation of other intracellular folate cofactors. Methotrexate 98-110 folylpolyglutamate synthase Homo sapiens 24-28 18025275-7 2007 However, the effects of FPGS modulation on the chemosensitivity of breast cancer cells to 5FU and methotrexate seem to be highly complex and depend not only on polyglutamylation of a specific target intracellular folate cofactor or methotrexate, respectively, but also on total intracellular folate pools and polyglutamylation of other intracellular folate cofactors. Methotrexate 232-244 folylpolyglutamate synthase Homo sapiens 24-28 16884772-0 2007 Molecular basis for decreased folylpoly-gamma-glutamate synthetase expression in a methotrexate resistant CCRF-CEM mutant cell line. Methotrexate 83-95 folylpolyglutamate synthase Homo sapiens 30-66 12439601-3 2002 To better understand these differences in MTXPG accumulation, we developed a model to characterize the cellular influx and efflux of MTX, formation of MTXPG by the addition of glutamyl residues catalyzed by FPGS (folylpolyglutamate synthetase), and cleavage of glutamyl residues from MTXPG by GGH (gamma-glutamyl hydrolase). Methotrexate 42-45 folylpolyglutamate synthase Homo sapiens 207-211 17286537-0 2007 Exploratory analysis of four polymorphisms in human GGH and FPGS genes and their effect in methotrexate-treated rheumatoid arthritis patients. Methotrexate 91-103 folylpolyglutamate synthase Homo sapiens 60-64 17286537-1 2007 The enzyme folylpoly-gamma-glutamase synthethase (FPGS) plays an important role in the intracellular polyglutamation of the disease-modifying antirheumatic drug methotrexate (MTX) and the length of the polyglutamated MTX product correlates with the time that MTX resides in the cell. Methotrexate 161-173 folylpolyglutamate synthase Homo sapiens 11-48 17286537-1 2007 The enzyme folylpoly-gamma-glutamase synthethase (FPGS) plays an important role in the intracellular polyglutamation of the disease-modifying antirheumatic drug methotrexate (MTX) and the length of the polyglutamated MTX product correlates with the time that MTX resides in the cell. Methotrexate 161-173 folylpolyglutamate synthase Homo sapiens 50-54 17286537-1 2007 The enzyme folylpoly-gamma-glutamase synthethase (FPGS) plays an important role in the intracellular polyglutamation of the disease-modifying antirheumatic drug methotrexate (MTX) and the length of the polyglutamated MTX product correlates with the time that MTX resides in the cell. Methotrexate 175-178 folylpolyglutamate synthase Homo sapiens 11-48 17286537-1 2007 The enzyme folylpoly-gamma-glutamase synthethase (FPGS) plays an important role in the intracellular polyglutamation of the disease-modifying antirheumatic drug methotrexate (MTX) and the length of the polyglutamated MTX product correlates with the time that MTX resides in the cell. Methotrexate 175-178 folylpolyglutamate synthase Homo sapiens 50-54 16707018-1 2006 BACKGROUND: Expression of folylpoly-gamma-glutamate synthetase (FPGS) gene is two- to three-fold higher in B-precursor ALL (Bp- ALL) than in T-lineage ALL (T-ALL) and correlates with intracellular accumulation of methotrexate (MTX) polyglutamates and lymphoblast sensitivity to MTX. Methotrexate 213-225 folylpolyglutamate synthase Homo sapiens 26-62 16707018-1 2006 BACKGROUND: Expression of folylpoly-gamma-glutamate synthetase (FPGS) gene is two- to three-fold higher in B-precursor ALL (Bp- ALL) than in T-lineage ALL (T-ALL) and correlates with intracellular accumulation of methotrexate (MTX) polyglutamates and lymphoblast sensitivity to MTX. Methotrexate 213-225 folylpolyglutamate synthase Homo sapiens 64-68 16707018-1 2006 BACKGROUND: Expression of folylpoly-gamma-glutamate synthetase (FPGS) gene is two- to three-fold higher in B-precursor ALL (Bp- ALL) than in T-lineage ALL (T-ALL) and correlates with intracellular accumulation of methotrexate (MTX) polyglutamates and lymphoblast sensitivity to MTX. Methotrexate 227-230 folylpolyglutamate synthase Homo sapiens 26-62 16707018-1 2006 BACKGROUND: Expression of folylpoly-gamma-glutamate synthetase (FPGS) gene is two- to three-fold higher in B-precursor ALL (Bp- ALL) than in T-lineage ALL (T-ALL) and correlates with intracellular accumulation of methotrexate (MTX) polyglutamates and lymphoblast sensitivity to MTX. Methotrexate 227-230 folylpolyglutamate synthase Homo sapiens 64-68 16707018-1 2006 BACKGROUND: Expression of folylpoly-gamma-glutamate synthetase (FPGS) gene is two- to three-fold higher in B-precursor ALL (Bp- ALL) than in T-lineage ALL (T-ALL) and correlates with intracellular accumulation of methotrexate (MTX) polyglutamates and lymphoblast sensitivity to MTX. Methotrexate 278-281 folylpolyglutamate synthase Homo sapiens 26-62 16707018-1 2006 BACKGROUND: Expression of folylpoly-gamma-glutamate synthetase (FPGS) gene is two- to three-fold higher in B-precursor ALL (Bp- ALL) than in T-lineage ALL (T-ALL) and correlates with intracellular accumulation of methotrexate (MTX) polyglutamates and lymphoblast sensitivity to MTX. Methotrexate 278-281 folylpolyglutamate synthase Homo sapiens 64-68 16707018-13 2006 Understanding the lineage-specific mechanisms of FPGS expression should lead to improved therapeutic strategies aimed at overcoming MTX resistance or inducing apoptosis in leukemic cells. Methotrexate 132-135 folylpolyglutamate synthase Homo sapiens 49-53 12673886-0 2003 Expression of folylpolyglutamyl synthetase predicts poor response to methotrexate therapy in patients with rheumatoid arthritis. Methotrexate 69-81 folylpolyglutamate synthase Homo sapiens 14-42 12673886-1 2003 OBJECTIVE: The enzyme folylpolyglutamyl synthetase (FPGS) is involved in the resistance to methotrexate in tumor cell lines. Methotrexate 91-103 folylpolyglutamate synthase Homo sapiens 22-50 12673886-1 2003 OBJECTIVE: The enzyme folylpolyglutamyl synthetase (FPGS) is involved in the resistance to methotrexate in tumor cell lines. Methotrexate 91-103 folylpolyglutamate synthase Homo sapiens 52-56 12673886-2 2003 The aim of the present study was to determine the impact of FPGS mRNA expression on resistance to methotrexate therapy in patients with rheumatoid arthritis (RA). Methotrexate 98-110 folylpolyglutamate synthase Homo sapiens 60-64 12673886-10 2003 Multivariate logistic regression analysis revealed that female sex (p = 0.009) and FPGS mRNA expression (p = 0.004) were independent predictive factors for failure to achieve a response to methotrexate therapy. Methotrexate 189-201 folylpolyglutamate synthase Homo sapiens 83-87 12673886-11 2003 CONCLUSION: FPGS mRNA expression is an independent predictive factor associated with poor response to methotrexate therapy in RA patients. Methotrexate 102-114 folylpolyglutamate synthase Homo sapiens 12-16 17286537-1 2007 The enzyme folylpoly-gamma-glutamase synthethase (FPGS) plays an important role in the intracellular polyglutamation of the disease-modifying antirheumatic drug methotrexate (MTX) and the length of the polyglutamated MTX product correlates with the time that MTX resides in the cell. Methotrexate 217-220 folylpolyglutamate synthase Homo sapiens 11-48 17286537-1 2007 The enzyme folylpoly-gamma-glutamase synthethase (FPGS) plays an important role in the intracellular polyglutamation of the disease-modifying antirheumatic drug methotrexate (MTX) and the length of the polyglutamated MTX product correlates with the time that MTX resides in the cell. Methotrexate 217-220 folylpolyglutamate synthase Homo sapiens 50-54 17286537-1 2007 The enzyme folylpoly-gamma-glutamase synthethase (FPGS) plays an important role in the intracellular polyglutamation of the disease-modifying antirheumatic drug methotrexate (MTX) and the length of the polyglutamated MTX product correlates with the time that MTX resides in the cell. Methotrexate 217-220 folylpolyglutamate synthase Homo sapiens 11-48 17286537-1 2007 The enzyme folylpoly-gamma-glutamase synthethase (FPGS) plays an important role in the intracellular polyglutamation of the disease-modifying antirheumatic drug methotrexate (MTX) and the length of the polyglutamated MTX product correlates with the time that MTX resides in the cell. Methotrexate 217-220 folylpolyglutamate synthase Homo sapiens 50-54 15542523-1 2004 BACKGROUND: Folylpoly-gamma-glutamate synthetase (FPGS) converts intracellular folates and antifolates (for example, methotrexate (MTX)) to polyglutamates. Methotrexate 117-129 folylpolyglutamate synthase Homo sapiens 12-48 15542523-1 2004 BACKGROUND: Folylpoly-gamma-glutamate synthetase (FPGS) converts intracellular folates and antifolates (for example, methotrexate (MTX)) to polyglutamates. Methotrexate 117-129 folylpolyglutamate synthase Homo sapiens 50-54 15542523-1 2004 BACKGROUND: Folylpoly-gamma-glutamate synthetase (FPGS) converts intracellular folates and antifolates (for example, methotrexate (MTX)) to polyglutamates. Methotrexate 131-134 folylpolyglutamate synthase Homo sapiens 12-48 15542523-1 2004 BACKGROUND: Folylpoly-gamma-glutamate synthetase (FPGS) converts intracellular folates and antifolates (for example, methotrexate (MTX)) to polyglutamates. Methotrexate 131-134 folylpolyglutamate synthase Homo sapiens 50-54 11187907-3 2000 Mechanisms of MTX resistance include (1) decreased transport via the reduced folate carrier (RFC), (2) altered levels of target enzymes, eg dihydrofolate reductase (DHFR) and thymidylate synthase (TS), (3) decreased ratio of folylpolyglutamate synthetase (FPGS)/folylpolyglutamate hydrolase (FPGH). Methotrexate 14-17 folylpolyglutamate synthase Homo sapiens 225-254 11187907-3 2000 Mechanisms of MTX resistance include (1) decreased transport via the reduced folate carrier (RFC), (2) altered levels of target enzymes, eg dihydrofolate reductase (DHFR) and thymidylate synthase (TS), (3) decreased ratio of folylpolyglutamate synthetase (FPGS)/folylpolyglutamate hydrolase (FPGH). Methotrexate 14-17 folylpolyglutamate synthase Homo sapiens 256-260 11187907-7 2000 Acute myeloid leukemia (AML) cells, considered MTX resistant, expressed two-fold lower levels of FPGS mRNA compared to c/preB-ALL (P = 0.04). Methotrexate 47-50 folylpolyglutamate synthase Homo sapiens 97-101 10470377-16 1999 The sensitivity of model cells, expressing a range of FPGS activities similar to that observed in leukemia blasts, to MTX varied over four orders of magnitude. Methotrexate 118-121 folylpolyglutamate synthase Homo sapiens 54-58 10500832-10 1999 Enzyme kinetics of the enzyme folylpolyglutamate synthetase (FPGS) were studied, demonstrating FPGS in the myeloid cell lines and patient samples had a higher K(m) for MTX as a substrate than lymphoid cells. Methotrexate 168-171 folylpolyglutamate synthase Homo sapiens 61-65 10500832-10 1999 Enzyme kinetics of the enzyme folylpolyglutamate synthetase (FPGS) were studied, demonstrating FPGS in the myeloid cell lines and patient samples had a higher K(m) for MTX as a substrate than lymphoid cells. Methotrexate 168-171 folylpolyglutamate synthase Homo sapiens 95-99 10777604-7 2000 Higher expression of hmFPGS relative to hcFPGS was observed in some sublines of CCRF-CEM with acquired MTX resistance suggesting that differential expression of the hmFPGS isoform may contribute to MTX resistance caused by decreased FPGS activity. Methotrexate 103-106 folylpolyglutamate synthase Homo sapiens 23-27 10777604-7 2000 Higher expression of hmFPGS relative to hcFPGS was observed in some sublines of CCRF-CEM with acquired MTX resistance suggesting that differential expression of the hmFPGS isoform may contribute to MTX resistance caused by decreased FPGS activity. Methotrexate 198-201 folylpolyglutamate synthase Homo sapiens 23-27 10499632-1 1999 The aim of this study was to investigate the influence of folylpolyglutamyl synthetase (FPGS) activity on the cellular pharmacology of the classical antifolates raltitrexed and methotrexate (MTX) using two human leukemia cell lines, CCRF-CEM and CCRF-CEM:RC2Tomudex. Methotrexate 177-189 folylpolyglutamate synthase Homo sapiens 58-86 10499632-1 1999 The aim of this study was to investigate the influence of folylpolyglutamyl synthetase (FPGS) activity on the cellular pharmacology of the classical antifolates raltitrexed and methotrexate (MTX) using two human leukemia cell lines, CCRF-CEM and CCRF-CEM:RC2Tomudex. Methotrexate 177-189 folylpolyglutamate synthase Homo sapiens 88-92 10499632-1 1999 The aim of this study was to investigate the influence of folylpolyglutamyl synthetase (FPGS) activity on the cellular pharmacology of the classical antifolates raltitrexed and methotrexate (MTX) using two human leukemia cell lines, CCRF-CEM and CCRF-CEM:RC2Tomudex. Methotrexate 191-194 folylpolyglutamate synthase Homo sapiens 58-86 10499632-1 1999 The aim of this study was to investigate the influence of folylpolyglutamyl synthetase (FPGS) activity on the cellular pharmacology of the classical antifolates raltitrexed and methotrexate (MTX) using two human leukemia cell lines, CCRF-CEM and CCRF-CEM:RC2Tomudex. Methotrexate 191-194 folylpolyglutamate synthase Homo sapiens 88-92 10507318-1 1999 We investigated the expression of the folylpolyglutamate synthetase (FPGS) gene at the mRNA level in MOLT-3 and K562 human leukemia cell lines sensitive, or made resistant, to methotrexate (MTX) and/or trimetrexate (TMQ), or raltitrexed (ZD1694). Methotrexate 176-188 folylpolyglutamate synthase Homo sapiens 38-67 10507318-1 1999 We investigated the expression of the folylpolyglutamate synthetase (FPGS) gene at the mRNA level in MOLT-3 and K562 human leukemia cell lines sensitive, or made resistant, to methotrexate (MTX) and/or trimetrexate (TMQ), or raltitrexed (ZD1694). Methotrexate 176-188 folylpolyglutamate synthase Homo sapiens 69-73 10507318-1 1999 We investigated the expression of the folylpolyglutamate synthetase (FPGS) gene at the mRNA level in MOLT-3 and K562 human leukemia cell lines sensitive, or made resistant, to methotrexate (MTX) and/or trimetrexate (TMQ), or raltitrexed (ZD1694). Methotrexate 190-193 folylpolyglutamate synthase Homo sapiens 38-67 10507318-1 1999 We investigated the expression of the folylpolyglutamate synthetase (FPGS) gene at the mRNA level in MOLT-3 and K562 human leukemia cell lines sensitive, or made resistant, to methotrexate (MTX) and/or trimetrexate (TMQ), or raltitrexed (ZD1694). Methotrexate 190-193 folylpolyglutamate synthase Homo sapiens 69-73 10507318-3 1999 A slight increase in the expression of the FPGS gene was observed in the TMQ-resistant MOLT-3 cells (MOLT-3/TMQ800); moreover, sequential development of MTX resistance in the TMQ-resistant cells (MOLT-3/TMQ800-MTX10,000) resulted in a further enhancement of FPGS mRNA expression despite of decreased polyglutamation capacity in this subline. Methotrexate 153-156 folylpolyglutamate synthase Homo sapiens 43-47 10507318-4 1999 Another MTX-resistant subline with impaired reduced folate carrier (MOLT-3/MTX10,000) also showed overexpression of FPGS mRNA. Methotrexate 8-11 folylpolyglutamate synthase Homo sapiens 116-120 10029597-0 1999 Role of folylpolyglutamate synthetase and folylpolyglutamate hydrolase in methotrexate accumulation and polyglutamylation in childhood leukemia. Methotrexate 74-86 folylpolyglutamate synthase Homo sapiens 8-37 10029597-8 1999 Multivariate analysis showed that FPGS, but not FPGH, was an independent contributor for MTX-Glu1-6 accumulation, but not for MTX-Glu4-6 accumulation. Methotrexate 89-92 folylpolyglutamate synthase Homo sapiens 34-38 10470377-17 1999 MTX toxicity was dependent on cytosolic FPGS activity as this drug does not enter the mitochondria, and cells expressing very high levels of FPGS solely in the mitochondria were resistant to MTX. Methotrexate 0-3 folylpolyglutamate synthase Homo sapiens 40-44 10470377-17 1999 MTX toxicity was dependent on cytosolic FPGS activity as this drug does not enter the mitochondria, and cells expressing very high levels of FPGS solely in the mitochondria were resistant to MTX. Methotrexate 191-194 folylpolyglutamate synthase Homo sapiens 141-145 9778690-1 1998 Synthesis of poly(gamma-glutamyl) metabolites of many antifolates, such as methotrexate (MTX), by folylpolyglutamate synthetase (FPGS) is often essential to their cytotoxic activity. Methotrexate 75-87 folylpolyglutamate synthase Homo sapiens 98-127 9778690-1 1998 Synthesis of poly(gamma-glutamyl) metabolites of many antifolates, such as methotrexate (MTX), by folylpolyglutamate synthetase (FPGS) is often essential to their cytotoxic activity. Methotrexate 75-87 folylpolyglutamate synthase Homo sapiens 129-133 9778690-1 1998 Synthesis of poly(gamma-glutamyl) metabolites of many antifolates, such as methotrexate (MTX), by folylpolyglutamate synthetase (FPGS) is often essential to their cytotoxic activity. Methotrexate 89-92 folylpolyglutamate synthase Homo sapiens 98-127 9778690-1 1998 Synthesis of poly(gamma-glutamyl) metabolites of many antifolates, such as methotrexate (MTX), by folylpolyglutamate synthetase (FPGS) is often essential to their cytotoxic activity. Methotrexate 89-92 folylpolyglutamate synthase Homo sapiens 129-133 9778690-2 1998 FPGS expression in the MTX-sensitive human T-lymphoblastic leukemia cell line CCRF-CEM and a number of MTX-resistant sublines was previously investigated at the DNA, RNA, and activity levels. Methotrexate 23-26 folylpolyglutamate synthase Homo sapiens 0-4 9778690-2 1998 FPGS expression in the MTX-sensitive human T-lymphoblastic leukemia cell line CCRF-CEM and a number of MTX-resistant sublines was previously investigated at the DNA, RNA, and activity levels. Methotrexate 103-106 folylpolyglutamate synthase Homo sapiens 0-4 9778690-6 1998 An MTX transport-defective line, however, displays both higher FPGS protein and activity levels. Methotrexate 3-6 folylpolyglutamate synthase Homo sapiens 63-67 9778690-7 1998 For several sublines in which the only apparent mechanism of MTX resistance is decreased FPGS activity, the FPGS protein level is decreased proportionally. Methotrexate 61-64 folylpolyglutamate synthase Homo sapiens 89-93 9778690-7 1998 For several sublines in which the only apparent mechanism of MTX resistance is decreased FPGS activity, the FPGS protein level is decreased proportionally. Methotrexate 61-64 folylpolyglutamate synthase Homo sapiens 108-112 9306433-0 1997 gamma-Glutamyl hydrolase and folylpolyglutamate synthetase activities predict polyglutamylation of methotrexate in acute leukemias. Methotrexate 99-111 folylpolyglutamate synthase Homo sapiens 29-58 9224825-5 1997 There was a significant relationship between FPGS mRNA and enzyme activity in lymphoblasts from children with newly diagnosed ALL, and blast FPGS mRNA and activity increased after methotrexate treatment. Methotrexate 180-192 folylpolyglutamate synthase Homo sapiens 45-49 9224825-5 1997 There was a significant relationship between FPGS mRNA and enzyme activity in lymphoblasts from children with newly diagnosed ALL, and blast FPGS mRNA and activity increased after methotrexate treatment. Methotrexate 180-192 folylpolyglutamate synthase Homo sapiens 141-145 9306433-2 1997 The steady-state level of long-chain MTX polyglutamates depends on the balance of activities of two enzymes: folylpolyglutamate synthetase (FPGS), which adds glutamates to MTX in a gamma-carboxyl linkage, and gamma-glutamyl hydrolase (GGH) or conjugase, which sequentially removes the terminal glutamate residue of MTX polyglutamates. Methotrexate 37-40 folylpolyglutamate synthase Homo sapiens 109-138 9306433-2 1997 The steady-state level of long-chain MTX polyglutamates depends on the balance of activities of two enzymes: folylpolyglutamate synthetase (FPGS), which adds glutamates to MTX in a gamma-carboxyl linkage, and gamma-glutamyl hydrolase (GGH) or conjugase, which sequentially removes the terminal glutamate residue of MTX polyglutamates. Methotrexate 37-40 folylpolyglutamate synthase Homo sapiens 140-144 9306433-4 1997 The ratio between GGH and FPGS activities was better at predicting the amount of polyglutamate accumulated in the 24-h [3H]MTX assay compared to the determination of either activity alone. Methotrexate 123-126 folylpolyglutamate synthase Homo sapiens 26-30 8608962-9 1996 However, folylpolyglutamate-synthetase(FPGS) mRNA was only moderately decreased in the 2 ZD1694-resistant sub-lines and to an even lesser extent in MOLT-3/MTX.p-9. Methotrexate 155-158 folylpolyglutamate synthase Homo sapiens 39-43 8568828-3 1996 Attempted ligation of DL-4,4-F2Glu to methotrexate (MTX), catalyzed by human folylpoly-gamma-glutamate synthetase (FPGS), revealed that DL-4,4-F2Glu is a poor alternate substrate. Methotrexate 38-50 folylpolyglutamate synthase Homo sapiens 77-113 8568828-3 1996 Attempted ligation of DL-4,4-F2Glu to methotrexate (MTX), catalyzed by human folylpoly-gamma-glutamate synthetase (FPGS), revealed that DL-4,4-F2Glu is a poor alternate substrate. Methotrexate 38-50 folylpolyglutamate synthase Homo sapiens 115-119 8568828-3 1996 Attempted ligation of DL-4,4-F2Glu to methotrexate (MTX), catalyzed by human folylpoly-gamma-glutamate synthetase (FPGS), revealed that DL-4,4-F2Glu is a poor alternate substrate. Methotrexate 52-55 folylpolyglutamate synthase Homo sapiens 77-113 8568828-3 1996 Attempted ligation of DL-4,4-F2Glu to methotrexate (MTX), catalyzed by human folylpoly-gamma-glutamate synthetase (FPGS), revealed that DL-4,4-F2Glu is a poor alternate substrate. Methotrexate 52-55 folylpolyglutamate synthase Homo sapiens 115-119 7890662-7 1995 Following growth of HL-60 cells with [3H]MTX, used as a model folate compound, a large reduction in its intracellular polyglutamate pools was shown during maturation which quantitatively reflected the decline in FPGS activity as well as folate transport inward (Sirotnak, F.M., Jacobson, D.M., and Yang, C-H. (1986) J. Biol. Methotrexate 41-44 folylpolyglutamate synthase Homo sapiens 212-216 7562910-13 1995 Further evaluation of the growth inhibitory activity of 3 against the MTX-resistant subline of CCRF-CEM cells (R30dm) with decreased FPGS indicated that poly-gamma-glutamylation was important for its action. Methotrexate 70-73 folylpolyglutamate synthase Homo sapiens 133-137 7517720-3 1994 We determined the expression of FPGS activity in blasts from children with ALL at diagnosis and after treatment with MTX as a single agent, before conventional remission induction therapy. Methotrexate 117-120 folylpolyglutamate synthase Homo sapiens 32-36 7517720-5 1994 Comparable lineage differences in normal lymphoid versus nonlymphoid cells suggest a lineage-specific control of FPGS expression, FPGS activity increased in ALL blasts after in vivo exposure to MTX. Methotrexate 194-197 folylpolyglutamate synthase Homo sapiens 113-117 7517720-5 1994 Comparable lineage differences in normal lymphoid versus nonlymphoid cells suggest a lineage-specific control of FPGS expression, FPGS activity increased in ALL blasts after in vivo exposure to MTX. Methotrexate 194-197 folylpolyglutamate synthase Homo sapiens 130-134 8408021-2 1993 Role of folylpoly-gamma-glutamate synthetase in methotrexate metabolism and cytotoxicity. Methotrexate 48-60 folylpolyglutamate synthase Homo sapiens 8-44 8408021-4 1993 CHO cells expressing human FPGS metabolized MTX to polyglutamates characteristic of human cells. Methotrexate 44-47 folylpolyglutamate synthase Homo sapiens 27-31 8408021-5 1993 Cellular MTX accumulation and metabolism to polyglutamates were dependent on the level of FPGS activity and were unaffected by putative gamma-glutamyl hydrolase inhibitors. Methotrexate 9-12 folylpolyglutamate synthase Homo sapiens 90-94 8408021-7 1993 After short term exposure to MTX, cells expressing higher levels of FPGS were more sensitive to the drug. Methotrexate 29-32 folylpolyglutamate synthase Homo sapiens 68-72