Matches in SemOpenAlex for { <https://semopenalex.org/work/W2409916698> ?p ?o ?g. }
Showing items 1 to 60 of
60
with 100 items per page.
- W2409916698 endingPage "5" @default.
- W2409916698 startingPage "61" @default.
- W2409916698 abstract "High-dose methotrexate (HDMTX) regimens were initially designed to overcome methotrexate (MTX) resistance due to defective transport of the drug. At high concentrations, enough MTX diffuses into resistant cells to saturate and inhibit the target enzyme, dihydrofolate reductase (DHFR). The high doses of MTX needed to achieve these high drug concentrations must be administered with the reduced folate antidote, leucovorin (LV; 5-formyltetrahydrofolate), to prevent increased toxicity. To increase MTX therapeutic index, LV rescue must be selective, i.e., more effective in normal than in tumor cells. In experimental models, selective rescue can be achieved if strict LV administration guidelines are respected. Since both MTX and LV use the membrane transport system, it was hypothesized that selective rescue occurred because transport-deficient, MTX-resistant tumor cells also transported LV poorly. The unsatisfactory clinical results frequently obtained with HDMTX regimens suggest a need to re-evaluate this underlying rationale, especially in view of recent findings concerning the mechanisms of MTX resistance and LV rescue. Experimentally, cells resistant to MTX because of an increased or altered DHFR, decreased metabolism to polyglutamates, or decreased thymidylate synthase activity are not always significantly more sensitive to higher concentrations of MTX. Furthermore, recent studies on human small cell lung cancer cell lines suggest that decreased MTX polyglutamate metabolism and thymidylate synthase activity might be prevalent MTX-resistant mechanisms in human tumors. Selective LV rescue could also occur through mechanisms other than selective uptake by normal tissues.(ABSTRACT TRUNCATED AT 250 WORDS)" @default.
- W2409916698 created "2016-06-24" @default.
- W2409916698 creator A5067138875 @default.
- W2409916698 date "1987-01-01" @default.
- W2409916698 modified "2023-09-23" @default.
- W2409916698 title "Biochemical and pharmacologic rationale for high-dose methotrexate." @default.
- W2409916698 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/2448656" @default.
- W2409916698 hasPublicationYear "1987" @default.
- W2409916698 type Work @default.
- W2409916698 sameAs 2409916698 @default.
- W2409916698 citedByCount "5" @default.
- W2409916698 countsByYear W24099166982021 @default.
- W2409916698 crossrefType "journal-article" @default.
- W2409916698 hasAuthorship W2409916698A5067138875 @default.
- W2409916698 hasConcept C123321153 @default.
- W2409916698 hasConcept C126322002 @default.
- W2409916698 hasConcept C19831878 @default.
- W2409916698 hasConcept C2776694085 @default.
- W2409916698 hasConcept C2778397455 @default.
- W2409916698 hasConcept C2780035454 @default.
- W2409916698 hasConcept C2780456651 @default.
- W2409916698 hasConcept C2781059491 @default.
- W2409916698 hasConcept C2781320022 @default.
- W2409916698 hasConcept C2781382166 @default.
- W2409916698 hasConcept C29730261 @default.
- W2409916698 hasConcept C71924100 @default.
- W2409916698 hasConcept C98274493 @default.
- W2409916698 hasConceptScore W2409916698C123321153 @default.
- W2409916698 hasConceptScore W2409916698C126322002 @default.
- W2409916698 hasConceptScore W2409916698C19831878 @default.
- W2409916698 hasConceptScore W2409916698C2776694085 @default.
- W2409916698 hasConceptScore W2409916698C2778397455 @default.
- W2409916698 hasConceptScore W2409916698C2780035454 @default.
- W2409916698 hasConceptScore W2409916698C2780456651 @default.
- W2409916698 hasConceptScore W2409916698C2781059491 @default.
- W2409916698 hasConceptScore W2409916698C2781320022 @default.
- W2409916698 hasConceptScore W2409916698C2781382166 @default.
- W2409916698 hasConceptScore W2409916698C29730261 @default.
- W2409916698 hasConceptScore W2409916698C71924100 @default.
- W2409916698 hasConceptScore W2409916698C98274493 @default.
- W2409916698 hasIssue "5" @default.
- W2409916698 hasLocation W24099166981 @default.
- W2409916698 hasOpenAccess W2409916698 @default.
- W2409916698 hasPrimaryLocation W24099166981 @default.
- W2409916698 hasRelatedWork W136397467 @default.
- W2409916698 hasRelatedWork W1537065657 @default.
- W2409916698 hasRelatedWork W1619766838 @default.
- W2409916698 hasRelatedWork W1974617422 @default.
- W2409916698 hasRelatedWork W2015027939 @default.
- W2409916698 hasRelatedWork W2114000036 @default.
- W2409916698 hasRelatedWork W2134043283 @default.
- W2409916698 hasRelatedWork W2169602887 @default.
- W2409916698 hasRelatedWork W2312586824 @default.
- W2409916698 hasRelatedWork W2409916698 @default.
- W2409916698 isParatext "false" @default.
- W2409916698 isRetracted "false" @default.
- W2409916698 magId "2409916698" @default.
- W2409916698 workType "article" @default.