Selective treatment of SCID mice bearing methotrexate-transport-resistant human acute lymphoblastic leukemia tumors with trimetrexate and leucovorin protection Journal Article
| Authors: | Lacerda, J. F.; Göker, E.; Kheradpour, A.; Dennig, D.; Elisseyeff, Y.; Jagiello, C.; O'Reilly, R. J.; Bertino, J. R. |
| Article Title: | Selective treatment of SCID mice bearing methotrexate-transport-resistant human acute lymphoblastic leukemia tumors with trimetrexate and leucovorin protection |
| Abstract: | Impaired transport of methotrexate (MTX) is a common resistance mechanism of tumor cells to this drug. Trimetrexate (TMTX), a second-generation folate antagonist, is still active against MTX-transport-resistant cells because it enters cells by passive diffusion and does not use the reduced folate transport system for cell entry. Therefore, although leucovorin (LV) protects MTX-sensitive cells from TMTX toxicity, MTX-transport defective cells are poorly rescued by LV. Severe combined immunodeficiency mice bearing MTX- transport-resistant CCRF-CEM acute lymphoblastic leukemia tumors were treated with TMTX alone or with the combination of TMTX and LV, with tumor regressions in both groups (P < .001) and without significant toxicity. These results indicate that TMTX with LV protection may be a useful therapeutic regimen for patients with MTX-transport-defective acute lymphoblastic leukemia. Furthermore, resistance to TMTX plus LV may result in reversion to MTX sensitivity. |
| Keywords: | human cell; nonhuman; methotrexate; animal cell; mouse; animal; mice; antineoplastic combined chemotherapy protocols; cytotoxicity; drug effect; drug resistance; mice, scid; acute lymphoblastic leukemia; folinic acid; leukemia cell; transplantation, heterologous; neoplasm transplantation; tumor growth; leucovorin; combined immunodeficiency; biological transport; tumor resistance; cell membrane transport; trimetrexate; protection; leukemia, lymphocytic, acute; active transport; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s. |
| Journal Title: | Blood |
| Volume: | 85 |
| Issue: | 10 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 1995-05-15 |
| Start Page: | 2675 |
| End Page: | 2679 |
| Language: | English |
| PUBMED: | 7742525 |
| PROVIDER: | scopus |
| DOI: | 10.1182/blood.V85.10.2675.bloodjournal85102675 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |
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