{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:22:26Z","timestamp":1790259746458,"version":"4.1.0"},"reference-count":29,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2009,12,1]],"date-time":"2009-12-01T00:00:00Z","timestamp":1259625600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Best Practice &amp; Research Clinical Haematology"],"published-print":{"date-parts":[[2009,12]]},"DOI":"10.1016\/j.beha.2009.09.004","type":"journal-article","created":{"date-parts":[[2009,12,2]],"date-time":"2009-12-02T10:19:00Z","timestamp":1259749140000},"page":"577-582","source":"Crossref","is-referenced-by-count":77,"title":["Cancer research: from folate antagonism to molecular targets"],"prefix":"10.1016","volume":"22","author":[{"given":"Joseph R.","family":"Bertino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.beha.2009.09.004_bib1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.3181\/00379727-97-23764","article-title":"Inhibition of dihydrofolic reductase by aminopterin and amethopterin","volume":"97","author":"Osborn","year":"1958","journal-title":"Proc Soc Exp Biol Med"},{"key":"10.1016\/j.beha.2009.09.004_bib2","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2008.20.8470","article-title":"Phase II-I-II Study of Two Different Doses and Schedules of Pralatrexate, a High-Affinity Substrate for the Reduced Folate Carrier, in Patients With Relapsed or Refractory Lymphoma Reveals Marked Activity in T-Cell Malignancies","author":"O'Connor","year":"2009","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.beha.2009.09.004_bib3","doi-asserted-by":"crossref","first-page":"6256","DOI":"10.1158\/1078-0432.CCR-04-0645","article-title":"Characterization of a folate transporter in HeLa cells with a low pH optimum and high affinity for pemetrexed distinct from the reduced folate carrier","volume":"10","author":"Wang","year":"2004","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.beha.2009.09.004_bib4","first-page":"1088","article-title":"Effectiveness of high-dose infusions of methotrexate followed by leucovorin in carcinoma of the head and neck","volume":"28","author":"Mitchell","year":"1968","journal-title":"Cancer Res"},{"key":"10.1016\/j.beha.2009.09.004_bib5","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1002\/1097-0142(197504)35:4<1050::AID-CNCR2820350406>3.0.CO;2-F","article-title":"Long-term remission in diffuse histiocytic lymphoma treated with combination sequential chemotherapy","volume":"35","author":"Berd","year":"1975","journal-title":"Cancer"},{"key":"10.1016\/j.beha.2009.09.004_bib6","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1016\/0006-2952(79)90655-5","article-title":"2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline (tmq), a potent non-classical folate antagonist inhibitor\u2013I effect on dihydrofolate reductase and growth of rodent tumors in vitro and in vivo","volume":"28","author":"Bertino","year":"1979","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.beha.2009.09.004_bib7","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1084\/jem.165.3.926","article-title":"Activity of antifolates against Pneumocystis carinii dihydrofolate reductase and identification of a potent new agent","volume":"165","author":"Allegra","year":"1987","journal-title":"J Exp Med"},{"key":"10.1016\/j.beha.2009.09.004_bib8","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1182\/blood.V85.10.2675.bloodjournal85102675","article-title":"Selective treatment of SCID mice bearing methotrexate-transport-resistant human acute lymphoblastic leukemia tumors with trimetrexate and leucovorin protection","volume":"85","author":"Lacerda","year":"1995","journal-title":"Blood"},{"key":"10.1016\/j.beha.2009.09.004_bib9","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1159\/000012112","article-title":"Sequential trimetrexate, 5-fluorouracil and folinic acid are effective and well tolerated in metastatic colorectal carcinoma. The phase II study group of the AIO","volume":"58","author":"Szelenyi","year":"2000","journal-title":"Oncology"},{"key":"10.1016\/j.beha.2009.09.004_bib10","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1097\/00001813-200103000-00003","article-title":"Phase I and pharmacokinetic study of the orally administered farnesyl transferase inhibitor R115777 in patients with advanced solid tumors","volume":"12","author":"Punt","year":"2001","journal-title":"Anticancer Drugs"},{"key":"10.1016\/j.beha.2009.09.004_bib11","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1093\/annonc\/mdf086","article-title":"Modulation of 5-fluorouracil\/leucovorin by trimetrexate\u2013did it work?","volume":"13","author":"Bertino","year":"2002","journal-title":"Ann Oncol"},{"key":"10.1016\/j.beha.2009.09.004_bib12","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/239395b0","article-title":"Enzymatic cleavage of methotrexate provides a method for prevention of drug toxicity","volume":"239","author":"Chabner","year":"1972","journal-title":"Nature"},{"key":"10.1016\/j.beha.2009.09.004_bib13","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1200\/JCO.1996.14.7.2145","article-title":"Carboxypeptidase G2 rescue after high-dose methotrexate","volume":"14","author":"DeAngelis","year":"1996","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.beha.2009.09.004_bib14","doi-asserted-by":"crossref","first-page":"147","DOI":"10.3109\/10428199309149127","article-title":"Asparaginase revisited","volume":"10","author":"Capizzi","year":"1993","journal-title":"Leuk Lymphoma"},{"key":"10.1016\/j.beha.2009.09.004_bib15","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/S0021-9258(17)34875-5","article-title":"Selective multiplication of dihydrofolate reductase genes in methotrexate-resistant variants of cultured murine cells","volume":"253","author":"Alt","year":"1978","journal-title":"J Biol Chem"},{"key":"10.1016\/j.beha.2009.09.004_bib16","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1056\/NEJM199610033351408","article-title":"Intrinsic and acquired resistance to methotrexate in acute leukemia","volume":"335","author":"Gorlick","year":"1996","journal-title":"N Engl J Med"},{"key":"10.1016\/j.beha.2009.09.004_bib17","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/978-1-59745-561-9_34","article-title":"Chemoprotection by transfer of resistance genes","volume":"542","author":"Budak-Alpdogan","year":"2009","journal-title":"Methods Mol Biol"},{"key":"10.1016\/j.beha.2009.09.004_bib18","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.ymthe.2004.06.115","article-title":"Methotrexate and cytarabine inhibit progression of human lymphoma in NOD\/SCID mice carrying a mutant dihydrofolate reductase and cytidine deaminase fusion gene","volume":"10","author":"Budak-Alpdogan","year":"2004","journal-title":"Mol Ther"},{"key":"10.1016\/j.beha.2009.09.004_bib19","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1126\/science.288.5466.669","article-title":"Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease","volume":"288","author":"Cavazzana-Calvo","year":"2000","journal-title":"Science"},{"key":"10.1016\/j.beha.2009.09.004_bib20","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1056\/NEJMp020184","article-title":"Risks and benefits of gene therapy","volume":"348","author":"Noguchi","year":"2003","journal-title":"N Engl J Med"},{"key":"10.1016\/j.beha.2009.09.004_bib21","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1172\/JCI31659","article-title":"Vector integration is nonrandom and clustered and influences the fate of lymphopoiesis in SCID-X1 gene therapy","volume":"117","author":"Deichmann","year":"2007","journal-title":"J Clin Invest"},{"key":"10.1016\/j.beha.2009.09.004_bib22","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1172\/JCI31666","article-title":"Multilineage hematopoietic reconstitution without clonal selection in ADA-SCID patients treated with stem cell gene therapy","volume":"117","author":"Aiuti","year":"2007","journal-title":"J Clin Invest"},{"key":"10.1016\/j.beha.2009.09.004_bib23","doi-asserted-by":"crossref","first-page":"11730","DOI":"10.1073\/pnas.0603635103","article-title":"Unique risk factors for insertional mutagenesis in a mouse model of XSCID gene therapy","volume":"103","author":"Shou","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.beha.2009.09.004_bib24","doi-asserted-by":"crossref","first-page":"12317","DOI":"10.1021\/bi971026e","article-title":"Dihydrofolate reductase protein inhibits its own translation by binding to dihydrofolate reductase mRNA sequences within the coding region","volume":"36","author":"Ercikan-Abali","year":"1997","journal-title":"Biochemistry"},{"key":"10.1016\/j.beha.2009.09.004_bib25","doi-asserted-by":"crossref","first-page":"4756","DOI":"10.1021\/bi00069a009","article-title":"Specific binding of human dihydrofolate reductase protein to dihydrofolate reductase messenger RNA in vitro","volume":"32","author":"Chu","year":"1993","journal-title":"Biochemistry"},{"key":"10.1016\/j.beha.2009.09.004_bib26","first-page":"621","article-title":"Mechanisms of methotrexate resistance in osteosarcoma","volume":"5","author":"Guo","year":"1999","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.beha.2009.09.004_bib27","first-page":"1952","article-title":"A novel single-nucleotide polymorphism in the 3'-untranslated region of the human dihydrofolate reductase gene with enhanced expression","volume":"7","author":"Goto","year":"2001","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.beha.2009.09.004_bib28","doi-asserted-by":"crossref","first-page":"13513","DOI":"10.1073\/pnas.0706217104","article-title":"A miR-24 microRNA binding-site polymorphism in dihydrofolate reductase gene leads to methotrexate resistance","volume":"104","author":"Mishra","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.beha.2009.09.004_bib29","doi-asserted-by":"crossref","first-page":"8080","DOI":"10.1158\/1078-0432.CCR-08-1422","article-title":"miR-192 Regulates dihydrofolate reductase and cellular proliferation through the p53-microRNA circuit","volume":"14","author":"Song","year":"2008","journal-title":"Clin Cancer Res"}],"container-title":["Best Practice &amp; Research Clinical Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1521692609000656?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1521692609000656?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T06:06:05Z","timestamp":1634277965000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1521692609000656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,12]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["S1521692609000656"],"URL":"https:\/\/doi.org\/10.1016\/j.beha.2009.09.004","relation":{},"ISSN":["1521-6926"],"issn-type":[{"value":"1521-6926","type":"print"}],"subject":[],"published":{"date-parts":[[2009,12]]}}}