Matches in SemOpenAlex for { <https://semopenalex.org/work/W2116968980> ?p ?o ?g. }
Showing items 1 to 93 of
93
with 100 items per page.
- W2116968980 abstract "We studied the consequences of interfering with DNA topoisomerase IIalpha (topo IIalpha) activity on melphalan-induced cytotoxicity. In order to accomplish our goal we used three different approaches to interfere with topo IIalpha. These include: i) use of three V79 Chinese hamster lung fibroblast-derived mutant cell lines, V507, V511, and V513 that are dysfunctional in topo IIalpha activity; ii) treatment of cells with etoposide (VP-16) which inhibits topo IIalpha through the formation of DNA-enzyme cleavable complex; and iii) exposure of cells to merbarone or ICRF-187 (Zinecard) that inhibits the activity of topo IIalpha by restricting its access to DNA. Based on clonogenic survival assays, all three approaches resulted in a significant potentiation of cytotoxicity of melphalan suggesting that topo IIalpha plays an important role in processing of DNA damage induced by melphalan. Furthermore, using alkaline elution assay, we show that melphalan-induced DNA cross-link formation and its repair is faster in V511 cells compared to the parental V79 cells. However, melphalan-induced sister chromatid exchanges (SCE) are found to be significantly higher in V511 cells compared to V79 cells. In addition, we find an excellent correlation between melphalan-induced SCE and cytotoxicity. These results could be explained on the assumption that topo IIalpha plays an important role in damage processing through excision repair of melphalan-induced DNA cross-links. However, in the absence of topo IIalpha the damages are primarily processed by recombination repair which may be prone to deleterious genetic alterations resulting in increased lethality as the frequency of recombination increases. In summary, our results demonstrate that: i) topo IIalpha deficiency is associated with increased sensitivity to melphalan; ii) deficiency of topo IIalpha is associated with an increase in melphalan-induced SCE; iii) increase in melphalan-induced SCE is associated with an increase in cytotoxicity; and iv) downregulation of topo IIalpha may be a useful approach to modulate the cytotoxicity of melphalan in combination chemotherapy regimens. These results have several important clinical implications. First, interference with topo IIalpha using agents such as VP-16 or ICRF-187 may provide a useful approach to enhance the efficacy of melphalan in combination chemotherapy regimens. Second, tumors which develop resistance to topo IIalpha-directed drugs due to quantitative or qualitative alterations in topo IIalpha may show increased susceptibility to a chemotherapy regimen containing melphalan." @default.
- W2116968980 created "2016-06-24" @default.
- W2116968980 creator A5007588723 @default.
- W2116968980 creator A5032644557 @default.
- W2116968980 creator A5037635525 @default.
- W2116968980 creator A5091627772 @default.
- W2116968980 date "2002-02-01" @default.
- W2116968980 modified "2023-09-26" @default.
- W2116968980 title "Interference with topoisomerase IIα potentiates melphalan cytotoxicity" @default.
- W2116968980 doi "https://doi.org/10.3892/ijo.20.2.311" @default.
- W2116968980 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11788894" @default.
- W2116968980 hasPublicationYear "2002" @default.
- W2116968980 type Work @default.
- W2116968980 sameAs 2116968980 @default.
- W2116968980 citedByCount "4" @default.
- W2116968980 countsByYear W21169689802012 @default.
- W2116968980 crossrefType "journal-article" @default.
- W2116968980 hasAuthorship W2116968980A5007588723 @default.
- W2116968980 hasAuthorship W2116968980A5032644557 @default.
- W2116968980 hasAuthorship W2116968980A5037635525 @default.
- W2116968980 hasAuthorship W2116968980A5091627772 @default.
- W2116968980 hasConcept C104317684 @default.
- W2116968980 hasConcept C109316439 @default.
- W2116968980 hasConcept C117262875 @default.
- W2116968980 hasConcept C143425029 @default.
- W2116968980 hasConcept C147897179 @default.
- W2116968980 hasConcept C153911025 @default.
- W2116968980 hasConcept C193104389 @default.
- W2116968980 hasConcept C202751555 @default.
- W2116968980 hasConcept C2776694085 @default.
- W2116968980 hasConcept C2778119113 @default.
- W2116968980 hasConcept C2778684742 @default.
- W2116968980 hasConcept C2779071816 @default.
- W2116968980 hasConcept C2780500152 @default.
- W2116968980 hasConcept C502942594 @default.
- W2116968980 hasConcept C54355233 @default.
- W2116968980 hasConcept C552990157 @default.
- W2116968980 hasConcept C55493867 @default.
- W2116968980 hasConcept C81885089 @default.
- W2116968980 hasConcept C86339819 @default.
- W2116968980 hasConcept C86803240 @default.
- W2116968980 hasConcept C94966510 @default.
- W2116968980 hasConcept C95444343 @default.
- W2116968980 hasConceptScore W2116968980C104317684 @default.
- W2116968980 hasConceptScore W2116968980C109316439 @default.
- W2116968980 hasConceptScore W2116968980C117262875 @default.
- W2116968980 hasConceptScore W2116968980C143425029 @default.
- W2116968980 hasConceptScore W2116968980C147897179 @default.
- W2116968980 hasConceptScore W2116968980C153911025 @default.
- W2116968980 hasConceptScore W2116968980C193104389 @default.
- W2116968980 hasConceptScore W2116968980C202751555 @default.
- W2116968980 hasConceptScore W2116968980C2776694085 @default.
- W2116968980 hasConceptScore W2116968980C2778119113 @default.
- W2116968980 hasConceptScore W2116968980C2778684742 @default.
- W2116968980 hasConceptScore W2116968980C2779071816 @default.
- W2116968980 hasConceptScore W2116968980C2780500152 @default.
- W2116968980 hasConceptScore W2116968980C502942594 @default.
- W2116968980 hasConceptScore W2116968980C54355233 @default.
- W2116968980 hasConceptScore W2116968980C552990157 @default.
- W2116968980 hasConceptScore W2116968980C55493867 @default.
- W2116968980 hasConceptScore W2116968980C81885089 @default.
- W2116968980 hasConceptScore W2116968980C86339819 @default.
- W2116968980 hasConceptScore W2116968980C86803240 @default.
- W2116968980 hasConceptScore W2116968980C94966510 @default.
- W2116968980 hasConceptScore W2116968980C95444343 @default.
- W2116968980 hasLocation W21169689801 @default.
- W2116968980 hasLocation W21169689802 @default.
- W2116968980 hasOpenAccess W2116968980 @default.
- W2116968980 hasPrimaryLocation W21169689801 @default.
- W2116968980 hasRelatedWork W1501188086 @default.
- W2116968980 hasRelatedWork W1567719786 @default.
- W2116968980 hasRelatedWork W1586329649 @default.
- W2116968980 hasRelatedWork W1598282819 @default.
- W2116968980 hasRelatedWork W1968293348 @default.
- W2116968980 hasRelatedWork W1979297684 @default.
- W2116968980 hasRelatedWork W1983009519 @default.
- W2116968980 hasRelatedWork W1987239902 @default.
- W2116968980 hasRelatedWork W2014550317 @default.
- W2116968980 hasRelatedWork W2038180581 @default.
- W2116968980 hasRelatedWork W2058959188 @default.
- W2116968980 hasRelatedWork W2059905649 @default.
- W2116968980 hasRelatedWork W2099238800 @default.
- W2116968980 hasRelatedWork W2122104782 @default.
- W2116968980 hasRelatedWork W2160957049 @default.
- W2116968980 hasRelatedWork W2300214082 @default.
- W2116968980 hasRelatedWork W2398520074 @default.
- W2116968980 hasRelatedWork W2405697486 @default.
- W2116968980 hasRelatedWork W2406125082 @default.
- W2116968980 hasRelatedWork W2942386843 @default.
- W2116968980 isParatext "false" @default.
- W2116968980 isRetracted "false" @default.
- W2116968980 magId "2116968980" @default.
- W2116968980 workType "article" @default.