{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T16:45:48Z","timestamp":1758991548581},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,6,6]],"date-time":"2007-06-06T00:00:00Z","timestamp":1181088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Many patients with retinoblastoma have a genetic predisposition to cancer and external beam radiation therapy and alkylating agent chemotherapy may increase their risk of secondary malignancy. Identification of effective chemotherapy agents for retinoblastoma that are not associated with an elevated risk of secondary malignancy would be beneficial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Twenty\u2010six specimens of fresh retinoblastoma tumor cells were studied in vitro with a PT430 competitive displacement assay. Differential displacement of the PT430 by methotrexate and not trimetrexate was considered indicative of a defect in reduced folate carrier (RFC)\u2010mediated transport. Elevations in the accumulation of PT430 were considered indicative of dihydrofolate reductase (DHFR) amplification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In 9 of the 26 (35%) samples, displacement by methotrexate was less than half the displacement by trimetrexate indicative of a defect in the RFC. In 5 of the 26 (19%) samples, trimetrexate did not displace the PT430. In 7 of 26 (27%) samples, the peak PT430 accumulation was suggestive of DHFR overexpression. Overall 9 of 26 (35%) samples had no evidence of a transport defect or DHFR overexpression and would be anticipated to be potentially sensitive to methotrexate. In 15 of the 26 (58%), no defects existed in trimetrexate displacement or DHFR overexpression and would be anticipated to be potentially sensitive to trimetrexate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results would support consideration of a phase II study to determine the effectiveness of trimetrexate for recurrent intra\u2010ocular retinoblastoma. Pediatr Blood Cancer 2008;50:573\u2013576. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.21266","type":"journal-article","created":{"date-parts":[[2007,6,6]],"date-time":"2007-06-06T21:48:21Z","timestamp":1181166501000},"page":"573-576","source":"Crossref","is-referenced-by-count":3,"title":["Impairments in antifolate transport are common in retinoblastoma tumor samples"],"prefix":"10.1002","volume":"50","author":[{"given":"Richard G.","family":"Gorlick","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H.","family":"Abramson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Sowers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth Anne","family":"Mazza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ira J.","family":"Dunkel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,1,9]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1996.01100140539004"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1996.01100140548005"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1996.01100140521001"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.1.12"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.120.12.1653"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(02)01348-X"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199610033351408"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1993.11.1.5"},{"key":"e_1_2_6_10_2","first-page":"469","article-title":"Chemosensitivity and multidrug resistance to antineoplastic drugs in retinoblastoma cell lines","volume":"9","author":"Chan HS","year":"1989","journal-title":"Anticancer Res"},{"key":"e_1_2_6_11_2","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1182\/blood.V80.5.1158.1158","article-title":"Defective transport as a mechanism of acquired resistance to methotrexate in patients with acute lymphocytic leukemia","volume":"80","author":"Trippett T","year":"1992","journal-title":"Blood"},{"key":"e_1_2_6_12_2","first-page":"621","article-title":"Mechanisms of methotrexate resistance in osteosarcoma","volume":"5","author":"Guo W","year":"1999","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.3.1013"},{"key":"e_1_2_6_14_2","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1182\/blood.V85.2.500.500","article-title":"Elevated dihydrofolate reductase and impaired methotrexate transport as elements in methotrexate resistance in childhood acute lymphocytic leukemia","volume":"85","author":"Matherly LH","year":"1995","journal-title":"Blood"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.05.054"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(98)94006-4"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(01)00562-0"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1201\/b14820-17"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006982-200412000-00002"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ohc.2004.11.002"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/88.5.270"},{"key":"e_1_2_6_22_2","doi-asserted-by":"crossref","first-page":"4182","DOI":"10.1200\/JCO.2001.19.21.4182","article-title":"Acute myeloblastic leukemia as a second malignancy in a patient with hereditary retinoblastoma","volume":"19","author":"Nishimura S","year":"2001","journal-title":"J Clin Oncol"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199902043400504"},{"key":"e_1_2_6_24_2","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 leukemia tumors with trimetrexate and leucovorin protection","volume":"85","author":"Lacerda JF","year":"1995","journal-title":"Blood"},{"key":"e_1_2_6_25_2","article-title":"Therapeutic responses in childhood acute lymphoblastic leukemia (ALL) and haplotypes of gamma glutamyl hydrolase (GGH) gene","author":"Garcia\u2010Bournissen F","year":"2006","journal-title":"Leuk Res"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1517\/14622416.5.7.819"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.10.3832"},{"key":"e_1_2_6_28_2","first-page":"1952","article-title":"A novel single\u2010nucleotide polymorphism in the 3'\u2010untranslated region of the human dihydrofolate reductase gene with enhanced expression","volume":"7","author":"Goto Y","year":"2001","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_29_2","first-page":"S18\u201071","article-title":"Trimetrexate: Experience with solid tumors","author":"Haller DG","year":"1997","journal-title":"Semin Oncol"},{"key":"e_1_2_6_30_2","first-page":"4973","article-title":"Pediatric phase I trial and pharmacokinetic study of trimetrexate","volume":"47","author":"Balis FM","year":"1987","journal-title":"Cancer Res"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/mpo.2950210409"},{"key":"e_1_2_6_32_2","first-page":"2981","article-title":"High\u2010dose trimetrexate and minimal\u2010dose leucovorin: a case for selective protection","volume":"4","author":"Hum M","year":"1998","journal-title":"Clin Cancer Res"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpbc.21266","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.21266","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T19:57:18Z","timestamp":1696881438000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.21266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,9]]},"references-count":31,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2008,3]]}},"alternative-id":["10.1002\/pbc.21266"],"URL":"https:\/\/doi.org\/10.1002\/pbc.21266","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,1,9]]}}}