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Chem."},{"key":"10.1016\/j.drup.2016.06.004_bib0355","first-page":"265","article-title":"Induction of mitochondrial mutations in human cells by methotrexate","volume":"31","author":"Hoar","year":"1985","journal-title":"Basic Life Sci."},{"key":"10.1016\/j.drup.2016.06.004_bib0360","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/BF02796468","article-title":"Methionine dependence in cancer cells \u2013 a review","volume":"18","author":"Hoffman","year":"1982","journal-title":"In Vitro"},{"key":"10.1016\/j.drup.2016.06.004_bib0365","doi-asserted-by":"crossref","first-page":"9038","DOI":"10.1074\/jbc.274.13.9038","article-title":"Inhibition of hypoxia-inducible factor 1 activation by carbon monoxide and nitric oxide. Implications for oxygen sensing and signaling","volume":"274","author":"Huang","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.drup.2016.06.004_bib0370","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s10930-009-9174-3","article-title":"Proteomic analysis of methylarginine-containing proteins in HeLa cells by two-dimensional gel electrophoresis and immunoblotting with a methylarginine-specific antibody","volume":"28","author":"Hung","year":"2009","journal-title":"Protein J."},{"key":"10.1016\/j.drup.2016.06.004_bib0375","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0083-6729(08)00404-4","article-title":"Molecular mechanisms of adaptation to folate deficiency","volume":"79","author":"Ifergan","year":"2008","journal-title":"Vitam. Horm."},{"key":"10.1016\/j.drup.2016.06.004_bib0380","doi-asserted-by":"crossref","first-page":"20687","DOI":"10.1074\/jbc.M802812200","article-title":"The reduced folate carrier (RFC) is cytotoxic to cells under conditions of severe folate deprivation. 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A."},{"key":"10.1016\/j.drup.2016.06.004_bib0435","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/j.addr.2004.01.002","article-title":"A review of folate receptor alpha cycling and 5-methyltetrahydrofolate accumulation with an emphasis on cell models in vitro","volume":"56","author":"Kamen","year":"2004","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.drup.2016.06.004_bib0440","doi-asserted-by":"crossref","first-page":"3288","DOI":"10.1182\/blood-2005-10-4048","article-title":"Coexistence of multiple mechanisms of PT523 resistance in human leukemia cells harboring 3 reduced folate carrier alleles: transcriptional silencing, inactivating mutations, and allele loss","volume":"107","author":"Kaufman","year":"2006","journal-title":"Blood"},{"key":"10.1016\/j.drup.2016.06.004_bib0445","doi-asserted-by":"crossref","first-page":"21680","DOI":"10.1016\/S0021-9258(20)80595-X","article-title":"Regulation of folate and one-carbon metabolism in mammalian cells. IV. 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Chem."},{"key":"10.1016\/j.drup.2016.06.004_bib0450","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1080\/713803569","article-title":"Variation of hepatic methotrexate 7-hydroxylase activity in animals and humans","volume":"48","author":"Kitamura","year":"1999","journal-title":"IUBMB Life"},{"key":"10.1016\/j.drup.2016.06.004_bib0455","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1126\/science.1227670","article-title":"Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer","volume":"339","author":"Kreso","year":"2013","journal-title":"Science"},{"key":"10.1016\/j.drup.2016.06.004_bib0460","first-page":"5020","article-title":"Interaction of polyglutamyl derivatives of methotrexate, 10-deazaaminopterin, and dihydrofolate with dihydrofolate reductase","volume":"46","author":"Kumar","year":"1986","journal-title":"Cancer Res."},{"key":"10.1016\/j.drup.2016.06.004_bib0465","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0304-3835(80)90117-2","article-title":"The role of 7-hydroxymethotrexate during methotrexate anti-cancer therapy","volume":"9","author":"Lankelma","year":"1980","journal-title":"Cancer Lett."},{"key":"10.1016\/j.drup.2016.06.004_bib0470","doi-asserted-by":"crossref","first-page":"29386","DOI":"10.1074\/jbc.M114.593244","article-title":"Mammalian mitochondrial and cytosolic folylpolyglutamate synthetase maintain the subcellular compartmentalization of folates","volume":"289","author":"Lawrence","year":"2014","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.drup.2016.06.004_bib0475","first-page":"942","article-title":"Folylpoly-gamma-glutamate synthetase gene mRNA splice variants and protein expression in primary human leukemia cells, cell lines, and normal human tissues","volume":"7","author":"Leclerc","year":"2001","journal-title":"Clin. 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Chem."},{"key":"10.1016\/j.drup.2016.06.004_bib0525","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/1475-2867-13-107","article-title":"FPGS rs1544105 polymorphism is associated with treatment outcome in pediatric B-cell precursor acute lymphoblastic leukemia","volume":"13","author":"Liu","year":"2013","journal-title":"Cancer Cell Int."},{"key":"10.1016\/j.drup.2016.06.004_bib0530","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nrc1074","article-title":"5-Fluorouracil: mechanisms of action and clinical strategies","volume":"3","author":"Longley","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.drup.2016.06.004_bib0535","doi-asserted-by":"crossref","first-page":"21665","DOI":"10.1016\/S0021-9258(20)80593-6","volume":"268","author":"Lowe","year":"1993","journal-title":"J. Biol. 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Horm."},{"key":"10.1016\/j.drup.2016.06.004_bib0595","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1021\/bi00551a005","article-title":"Interactions of pig liver methylenetetrahydrofolate reductase with methylenetetrahydropteroylpolyglutamate substrates and with dihydropteroylpolyglutamate inhibitors","volume":"19","author":"Matthews","year":"1980","journal-title":"Biochemistry"},{"key":"10.1016\/j.drup.2016.06.004_bib0600","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0065-2571(87)90012-4","article-title":"Folylpolyglutamates as substrates and inhibitors of folate-dependent enzymes","volume":"26","author":"Matthews","year":"1987","journal-title":"Adv. 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Chem."},{"key":"10.1016\/j.drup.2016.06.004_bib0620","doi-asserted-by":"crossref","first-page":"6181","DOI":"10.1016\/S0021-9258(18)38101-8","article-title":"Decreased folylpolyglutamate synthetase activity as a mechanism of methotrexate resistance in CCRF-CEM human leukemia sublines","volume":"266","author":"McCloskey","year":"1991","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.drup.2016.06.004_bib0625","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.2174\/1381612033453712","article-title":"Anticancer antifolates: current status and future directions","volume":"9","author":"McGuire","year":"2003","journal-title":"Curr. Pharm. Des."},{"key":"10.1016\/j.drup.2016.06.004_bib0630","first-page":"535","article-title":"Evolution of drug resistance in CCRF-CEM human leukemia cells selected by intermittent methotrexate exposure","volume":"7","author":"McGuire","year":"1995","journal-title":"Oncol. Res."},{"key":"10.1016\/j.drup.2016.06.004_bib0635","first-page":"1996","article-title":"Cross-resistance studies of folylpolyglutamate synthetase-deficient, methotrexate-resistant CCRF-CEM human leukemia sublines","volume":"7","author":"McGuire","year":"1993","journal-title":"Leukemia"},{"key":"10.1016\/j.drup.2016.06.004_bib0640","doi-asserted-by":"crossref","first-page":"5776","DOI":"10.1016\/S0021-9258(19)70697-8","article-title":"Enzymatic synthesis of folylpolyglutamates. Characterization of the reaction and its products","volume":"255","author":"McGuire","year":"1980","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.drup.2016.06.004_bib0645","first-page":"6395","article-title":"Role of methotrexate polyglutamates in methotrexate- and sequential methotrexate-5-fluorouracil-mediated cell kill","volume":"45","author":"McGuire","year":"1985","journal-title":"Cancer Res."},{"key":"10.1016\/j.drup.2016.06.004_bib0650","first-page":"193","article-title":"Folylpolyglutamate synthetase expression in antifolate-sensitive and -resistant human cell lines","volume":"10","author":"McGuire","year":"1998","journal-title":"Oncol. Res."},{"key":"10.1016\/j.drup.2016.06.004_bib0655","doi-asserted-by":"crossref","first-page":"13012","DOI":"10.1074\/jbc.275.17.13012","article-title":"Human cytosolic and mitochondrial folylpolyglutamate synthetase are electrophoretically distinct. Expression in antifolate-sensitive and -resistant human cell lines","volume":"275","author":"McGuire","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.drup.2016.06.004_bib0660","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/BF00194535","article-title":"Exploitation of folate and antifolate polyglutamylation to achieve selective anticancer chemotherapy","volume":"14","author":"McGuire","year":"1996","journal-title":"Invest. New Drugs"},{"key":"10.1016\/j.drup.2016.06.004_bib0665","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.1365-313X.2010.04336.x","article-title":"Functional analysis of folate polyglutamylation and its essential role in plant metabolism and development","volume":"64","author":"Mehrshahi","year":"2010","journal-title":"Plant J."},{"key":"10.1016\/j.drup.2016.06.004_bib0670","doi-asserted-by":"crossref","first-page":"9079","DOI":"10.1038\/srep09079","article-title":"Association of FPGS genetic polymorphisms with primary retroperitoneal liposarcoma","volume":"5","author":"Miao","year":"2015","journal-title":"Sci. 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