FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3048373112> ?p ?o ?g. }

• W3048373112 abstract "High-dose methotrexate is a cornerstone agent in the chemotherapeutic treatment of patients with osteosarcoma. However, patients often develop methotrexate-induced toxicities. We aim to identify determinants of methotrexate-induced toxicities in osteosarcoma patients by investigating the relation between drug plasma levels, methotrexate-induced toxicities, and germline variants in genes related to drug absorption, distribution, metabolism, and elimination. A cohort of 114 osteosarcoma patients was genotyped for 1,931 variants in 231 genes using the Drug Metabolism Enzymes and Transporters Plus array. Methotrexate plasma levels and laboratory measurements during and after high-dose methotrexate treatment concerning renal function, liver damage, and myelopoiesis to reflect toxicity outcomes were obtained. One hundred and thirteen patients and a subset of 545 variants in 176 genes passed quality control checks. Methotrexate plasma levels showed associations with creatinine, alanine aminotransferase, and hemoglobin. Genetic variant rs3736599 in the 5'-untranslated region of SULT1E1 was associated with lower 48 hour methotrexate plasma levels [coef -0.313 (95% CI -0.459 - -0.167); p = 2.60 × 10-5]. Association with methotrexate-induced decreased thrombocyte counts was found for two intronic variants in CYP2B6 {rs4803418 [coef -0.187 (95% CI -0.275 - -0.099); p = 3.04 × 10-5] and rs4803419 [coef -0.186 (95% CI -0.278 - -0.093); p = 8.80 × 10-5]}. An association with increased thrombocyte counts was identified for the intronic variant rs4808326 in CYP4F8 [coef 0.193 (95% CI 0.099 - 0.287); p = 6.02 × 10-5]. Moreover, a secondary analysis with a binary approach using CTCAE toxicity criteria resulted in a nominal significant associations (p < 0.05) for two out of three variants (rs4803418 and rs4808326). This is the first study to identify genetic variants in SULT1E1, CYP2B6, and CYP4F8 to be associated with methotrexate pharmacokinetics and toxicities. Validation of these variants in an independent cohort and further functional investigation of variants in the identified genes is needed to determine if and how they affect methotrexate plasma levels and the development of methotrexate-induced toxicities." @default.
• W3048373112 created "2020-08-18" @default.
• W3048373112 creator A5004194069 @default.
• W3048373112 creator A5025935523 @default.
• W3048373112 creator A5033645413 @default.
• W3048373112 creator A5037151292 @default.
• W3048373112 creator A5040793363 @default.
• W3048373112 creator A5054734188 @default.
• W3048373112 creator A5064691832 @default.
• W3048373112 creator A5069495532 @default.
• W3048373112 creator A5073191678 @default.
• W3048373112 creator A5076321542 @default.
• W3048373112 creator A5079496433 @default.
• W3048373112 date "2020-08-12" @default.
• W3048373112 modified "2023-10-16" @default.
• W3048373112 title "Analysis of Drug Metabolizing Gene Panel in Osteosarcoma Patients Identifies Association Between Variants in SULT1E1, CYP2B6 and CYP4F8 and Methotrexate Levels and Toxicities" @default.
• W3048373112 cites W1598956904 @default.
• W3048373112 cites W1656539109 @default.
• W3048373112 cites W1664168469 @default.
• W3048373112 cites W1828199879 @default.
• W3048373112 cites W1965210135 @default.
• W3048373112 cites W1971035689 @default.
• W3048373112 cites W1975903555 @default.
• W3048373112 cites W1981527886 @default.
• W3048373112 cites W1987178620 @default.
• W3048373112 cites W2007548292 @default.
• W3048373112 cites W2011669229 @default.
• W3048373112 cites W2013623834 @default.
• W3048373112 cites W2016058563 @default.
• W3048373112 cites W2017050568 @default.
• W3048373112 cites W2018780534 @default.
• W3048373112 cites W2018838463 @default.
• W3048373112 cites W2019688507 @default.
• W3048373112 cites W2035815658 @default.
• W3048373112 cites W2038526706 @default.
• W3048373112 cites W2056941568 @default.
• W3048373112 cites W2063280109 @default.
• W3048373112 cites W2063469101 @default.
• W3048373112 cites W2063693592 @default.
• W3048373112 cites W2063725536 @default.
• W3048373112 cites W2075744546 @default.
• W3048373112 cites W2077718321 @default.
• W3048373112 cites W2077746558 @default.
• W3048373112 cites W2079675818 @default.
• W3048373112 cites W2112309180 @default.
• W3048373112 cites W2114076312 @default.
• W3048373112 cites W2118783447 @default.
• W3048373112 cites W2129471193 @default.
• W3048373112 cites W2133829107 @default.
• W3048373112 cites W2141820415 @default.
• W3048373112 cites W2147327697 @default.
• W3048373112 cites W2155766871 @default.
• W3048373112 cites W2166320441 @default.
• W3048373112 cites W2187779543 @default.
• W3048373112 cites W2322263796 @default.
• W3048373112 cites W2329218644 @default.
• W3048373112 cites W2329372490 @default.
• W3048373112 cites W2501152284 @default.
• W3048373112 cites W2613180806 @default.
• W3048373112 cites W2617130599 @default.
• W3048373112 cites W2801625303 @default.
• W3048373112 cites W2804686050 @default.
• W3048373112 doi "https://doi.org/10.3389/fphar.2020.01241" @default.
• W3048373112 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7435008" @default.
• W3048373112 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32903464" @default.
• W3048373112 hasPublicationYear "2020" @default.
• W3048373112 type Work @default.
• W3048373112 sameAs 3048373112 @default.
• W3048373112 citedByCount "6" @default.
• W3048373112 countsByYear W30483731122021 @default.
• W3048373112 countsByYear W30483731122022 @default.
• W3048373112 countsByYear W30483731122023 @default.
• W3048373112 crossrefType "journal-article" @default.
• W3048373112 hasAuthorship W3048373112A5004194069 @default.
• W3048373112 hasAuthorship W3048373112A5025935523 @default.
• W3048373112 hasAuthorship W3048373112A5033645413 @default.
• W3048373112 hasAuthorship W3048373112A5037151292 @default.
• W3048373112 hasAuthorship W3048373112A5040793363 @default.
• W3048373112 hasAuthorship W3048373112A5054734188 @default.
• W3048373112 hasAuthorship W3048373112A5064691832 @default.
• W3048373112 hasAuthorship W3048373112A5069495532 @default.
• W3048373112 hasAuthorship W3048373112A5073191678 @default.
• W3048373112 hasAuthorship W3048373112A5076321542 @default.
• W3048373112 hasAuthorship W3048373112A5079496433 @default.
• W3048373112 hasBestOaLocation W30483731121 @default.
• W3048373112 hasConcept C104317684 @default.
• W3048373112 hasConcept C126322002 @default.
• W3048373112 hasConcept C135763542 @default.
• W3048373112 hasConcept C143998085 @default.
• W3048373112 hasConcept C2776598434 @default.
• W3048373112 hasConcept C2781059491 @default.
• W3048373112 hasConcept C43563269 @default.
• W3048373112 hasConcept C54355233 @default.
• W3048373112 hasConcept C55775858 @default.
• W3048373112 hasConcept C71924100 @default.
• W3048373112 hasConcept C86803240 @default.
• W3048373112 hasConcept C90924648 @default.
• W3048373112 hasConcept C98274493 @default.
• W3048373112 hasConceptScore W3048373112C104317684 @default.
• W3048373112 hasConceptScore W3048373112C126322002 @default.

• next