FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1994523215> ?p ?o ?g. }

• W1994523215 endingPage "773" @default.
• W1994523215 startingPage "767" @default.
• W1994523215 abstract "Myelosuppression is one of the major side effects of most anticancer drugs. To confer myeloprotection, our laboratory generated drug-resistant mutants of select target human enzymes for gene transfer to the bone marrow. Mutants of two of these enzymes, dihydrofolate reductase (DHFR F/S) and thymidylate synthase (TS G52S), were previously shown to confer resistance to methotrexate and 5-FU, respectively, and recently a fusion cDNA of both mutant enzymes (DHFR F/S-TS G52S) was shown to confer dual resistance to both antimetabolites. In this study, we examined the sensitivity of the DHFR F/S-TS G52S fusion protein to the multitargeted antifolate, pemetrexed (LY231514, Alimta), which targets both DHFR and TS and is currently in phase III trials for the treatment of solid tumors and in combination with cisplatin has been shown to be an advance in the treatment of mesothelioma. The K(i) for the DHFR F/S portion of the purified fusion protein to pemetrexed was increased by greater than 9000-fold when compared to wtDHFR (8000 versus 0.86 nM), while the K(i) for the TS G52S portion of the fusion protein to pemetrexed was similar to that of wtTS (2.8 versus 3.1 nM). When the fusion gene was retrovirally transduced into NIH 3T3 fibroblasts, the IC(50) to pemetrexed was three- to four-fold higher than cells transduced with DHFR F/S or TS G52S alone (163 versus 53 and 45 nM, respectively). Similarly, expression of the DHFR F/S-TS G52S fusion gene in retrovirally transduced mouse marrow cells resulted in an increased survival of CFU-GM colonies when compared to cells transduced with either of the mutants alone. Co-expression of mutant DHFR and TS enzymes has additive effects in conferring resistance to pemetrexed-induced toxicity. This construct may be useful for conferring myeloprotection to patients receiving this drug." @default.
• W1994523215 created "2016-06-24" @default.
• W1994523215 creator A5006868141 @default.
• W1994523215 creator A5012047866 @default.
• W1994523215 creator A5026438002 @default.
• W1994523215 creator A5027001679 @default.
• W1994523215 creator A5064988009 @default.
• W1994523215 creator A5068505847 @default.
• W1994523215 creator A5082874698 @default.
• W1994523215 creator A5090964554 @default.
• W1994523215 date "2004-09-10" @default.
• W1994523215 modified "2023-10-18" @default.
• W1994523215 title "Protection of hematopoietic stem cells from pemetrexed toxicity by retroviral gene transfer with a mutant dihydrofolate reductase-mutant thymidylate synthase fusion gene" @default.
• W1994523215 cites W16336426 @default.
• W1994523215 cites W1963844573 @default.
• W1994523215 cites W1967656190 @default.
• W1994523215 cites W1975243176 @default.
• W1994523215 cites W1984219340 @default.
• W1994523215 cites W2013908437 @default.
• W1994523215 cites W2016758458 @default.
• W1994523215 cites W2017072211 @default.
• W1994523215 cites W2019491580 @default.
• W1994523215 cites W2033710051 @default.
• W1994523215 cites W2044519843 @default.
• W1994523215 cites W2072252524 @default.
• W1994523215 cites W2084709487 @default.
• W1994523215 cites W2090281205 @default.
• W1994523215 cites W2102627969 @default.
• W1994523215 cites W2175264506 @default.
• W1994523215 cites W2200991233 @default.
• W1994523215 cites W2210033643 @default.
• W1994523215 cites W2411515331 @default.
• W1994523215 cites W4243932715 @default.
• W1994523215 cites W4247590927 @default.
• W1994523215 cites W4360754311 @default.
• W1994523215 doi "https://doi.org/10.1038/sj.cgt.7700683" @default.
• W1994523215 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15359285" @default.
• W1994523215 hasPublicationYear "2004" @default.
• W1994523215 type Work @default.
• W1994523215 sameAs 1994523215 @default.
• W1994523215 citedByCount "17" @default.
• W1994523215 countsByYear W19945232152012 @default.
• W1994523215 countsByYear W19945232152013 @default.
• W1994523215 countsByYear W19945232152015 @default.
• W1994523215 countsByYear W19945232152017 @default.
• W1994523215 countsByYear W19945232152019 @default.
• W1994523215 crossrefType "journal-article" @default.
• W1994523215 hasAuthorship W1994523215A5006868141 @default.
• W1994523215 hasAuthorship W1994523215A5012047866 @default.
• W1994523215 hasAuthorship W1994523215A5026438002 @default.
• W1994523215 hasAuthorship W1994523215A5027001679 @default.
• W1994523215 hasAuthorship W1994523215A5064988009 @default.
• W1994523215 hasAuthorship W1994523215A5068505847 @default.
• W1994523215 hasAuthorship W1994523215A5082874698 @default.
• W1994523215 hasAuthorship W1994523215A5090964554 @default.
• W1994523215 hasBestOaLocation W19945232151 @default.
• W1994523215 hasConcept C104317684 @default.
• W1994523215 hasConcept C111829193 @default.
• W1994523215 hasConcept C123321153 @default.
• W1994523215 hasConcept C123894998 @default.
• W1994523215 hasConcept C143065580 @default.
• W1994523215 hasConcept C153911025 @default.
• W1994523215 hasConcept C181199279 @default.
• W1994523215 hasConcept C185592680 @default.
• W1994523215 hasConcept C203014093 @default.
• W1994523215 hasConcept C2776694085 @default.
• W1994523215 hasConcept C2777240266 @default.
• W1994523215 hasConcept C2778239845 @default.
• W1994523215 hasConcept C2778397455 @default.
• W1994523215 hasConcept C2780456651 @default.
• W1994523215 hasConcept C2781059491 @default.
• W1994523215 hasConcept C2781320022 @default.
• W1994523215 hasConcept C2781382166 @default.
• W1994523215 hasConcept C40767141 @default.
• W1994523215 hasConcept C54355233 @default.
• W1994523215 hasConcept C55493867 @default.
• W1994523215 hasConcept C86803240 @default.
• W1994523215 hasConceptScore W1994523215C104317684 @default.
• W1994523215 hasConceptScore W1994523215C111829193 @default.
• W1994523215 hasConceptScore W1994523215C123321153 @default.
• W1994523215 hasConceptScore W1994523215C123894998 @default.
• W1994523215 hasConceptScore W1994523215C143065580 @default.
• W1994523215 hasConceptScore W1994523215C153911025 @default.
• W1994523215 hasConceptScore W1994523215C181199279 @default.
• W1994523215 hasConceptScore W1994523215C185592680 @default.
• W1994523215 hasConceptScore W1994523215C203014093 @default.
• W1994523215 hasConceptScore W1994523215C2776694085 @default.
• W1994523215 hasConceptScore W1994523215C2777240266 @default.
• W1994523215 hasConceptScore W1994523215C2778239845 @default.
• W1994523215 hasConceptScore W1994523215C2778397455 @default.
• W1994523215 hasConceptScore W1994523215C2780456651 @default.
• W1994523215 hasConceptScore W1994523215C2781059491 @default.
• W1994523215 hasConceptScore W1994523215C2781320022 @default.
• W1994523215 hasConceptScore W1994523215C2781382166 @default.
• W1994523215 hasConceptScore W1994523215C40767141 @default.
• W1994523215 hasConceptScore W1994523215C54355233 @default.
• W1994523215 hasConceptScore W1994523215C55493867 @default.
• W1994523215 hasConceptScore W1994523215C86803240 @default.

• next