Matches in SemOpenAlex for { <https://semopenalex.org/work/W4377029658> ?p ?o ?g. }
Showing items 1 to 75 of
75
with 100 items per page.
- W4377029658 abstract "<b>Abstract ID 23594</b> <b>Poster Board 249</b> Chemotherapy has remained the mainstay for the treatment of multiple types of cancers. In particular, topical use of chemotherapy has been used for skin cancers. Though effective, topical chemotherapy has been limited due to adverse effects such as local and even systemic toxicities. Our recent studies demonstrated that exposure to pro-oxidative stressors, including therapeutic agents induces the generation of extracellular vesicles known as microvesicle particles (MVP) which are dependent on activation of the Platelet-activating factor-receptor (PAFR), a G-protein coupled receptor present on various cell types, and acid sphingomyelinase (aSMase), an enzyme required for MVP biogenesis. Based upon this premise, we tested the hypothesis that topical application of gemcitabine will induce MVP generation in human and murine skin. Our <i>ex vivo</i> studies using human skin explants demonstrate that gemcitabine treatment results in MVP generation in a dose-dependent manner in a process blocked by PAFR antagonist and aSMase inhibitor. Importantly, gemcitabine-induced MVPs carry PAFR agonists. To confirm the mechanisms, we employed PAFR-expressing and deficient (<i>Ptafr<sup>-/-</sup></i>) mouse models as well as mice deficient in aSMase enzyme (<i>Spmd1<sup>-/-</sup></i>). Using genetic-based approaches, our studies demonstrated that gemcitabine-induced MVP release in WT mice was blunted in <i>Ptafr<sup>-/-</sup></i> and <i>Spmd1<sup>-/-</sup></i> mice. Overall, these findings indicate that pharmacological strategies to target the PAFR/aSMase pathway to block MVP release could be used as a promising approach for improving gemcitabine efficacy." @default.
- W4377029658 created "2023-05-19" @default.
- W4377029658 creator A5010914920 @default.
- W4377029658 creator A5022230642 @default.
- W4377029658 creator A5028851840 @default.
- W4377029658 creator A5032644073 @default.
- W4377029658 creator A5049243484 @default.
- W4377029658 creator A5055174770 @default.
- W4377029658 creator A5072908204 @default.
- W4377029658 creator A5074366734 @default.
- W4377029658 date "2023-05-18" @default.
- W4377029658 modified "2023-09-29" @default.
- W4377029658 title "Significance of topical chemotherapy application on human and murine skin" @default.
- W4377029658 doi "https://doi.org/10.1124/jpet.122.235940" @default.
- W4377029658 hasPublicationYear "2023" @default.
- W4377029658 type Work @default.
- W4377029658 citedByCount "0" @default.
- W4377029658 crossrefType "proceedings-article" @default.
- W4377029658 hasAuthorship W4377029658A5010914920 @default.
- W4377029658 hasAuthorship W4377029658A5022230642 @default.
- W4377029658 hasAuthorship W4377029658A5028851840 @default.
- W4377029658 hasAuthorship W4377029658A5032644073 @default.
- W4377029658 hasAuthorship W4377029658A5049243484 @default.
- W4377029658 hasAuthorship W4377029658A5055174770 @default.
- W4377029658 hasAuthorship W4377029658A5072908204 @default.
- W4377029658 hasAuthorship W4377029658A5074366734 @default.
- W4377029658 hasBestOaLocation W43770296581 @default.
- W4377029658 hasConcept C126322002 @default.
- W4377029658 hasConcept C150903083 @default.
- W4377029658 hasConcept C185592680 @default.
- W4377029658 hasConcept C190283241 @default.
- W4377029658 hasConcept C207001950 @default.
- W4377029658 hasConcept C26291073 @default.
- W4377029658 hasConcept C2776694085 @default.
- W4377029658 hasConcept C2777851122 @default.
- W4377029658 hasConcept C2780258809 @default.
- W4377029658 hasConcept C2781457462 @default.
- W4377029658 hasConcept C502942594 @default.
- W4377029658 hasConcept C55493867 @default.
- W4377029658 hasConcept C71924100 @default.
- W4377029658 hasConcept C86803240 @default.
- W4377029658 hasConcept C95444343 @default.
- W4377029658 hasConcept C98274493 @default.
- W4377029658 hasConceptScore W4377029658C126322002 @default.
- W4377029658 hasConceptScore W4377029658C150903083 @default.
- W4377029658 hasConceptScore W4377029658C185592680 @default.
- W4377029658 hasConceptScore W4377029658C190283241 @default.
- W4377029658 hasConceptScore W4377029658C207001950 @default.
- W4377029658 hasConceptScore W4377029658C26291073 @default.
- W4377029658 hasConceptScore W4377029658C2776694085 @default.
- W4377029658 hasConceptScore W4377029658C2777851122 @default.
- W4377029658 hasConceptScore W4377029658C2780258809 @default.
- W4377029658 hasConceptScore W4377029658C2781457462 @default.
- W4377029658 hasConceptScore W4377029658C502942594 @default.
- W4377029658 hasConceptScore W4377029658C55493867 @default.
- W4377029658 hasConceptScore W4377029658C71924100 @default.
- W4377029658 hasConceptScore W4377029658C86803240 @default.
- W4377029658 hasConceptScore W4377029658C95444343 @default.
- W4377029658 hasConceptScore W4377029658C98274493 @default.
- W4377029658 hasLocation W43770296581 @default.
- W4377029658 hasOpenAccess W4377029658 @default.
- W4377029658 hasPrimaryLocation W43770296581 @default.
- W4377029658 hasRelatedWork W1947741425 @default.
- W4377029658 hasRelatedWork W2004172311 @default.
- W4377029658 hasRelatedWork W2013765863 @default.
- W4377029658 hasRelatedWork W2037182962 @default.
- W4377029658 hasRelatedWork W2084547689 @default.
- W4377029658 hasRelatedWork W2463515876 @default.
- W4377029658 hasRelatedWork W2748952813 @default.
- W4377029658 hasRelatedWork W2899084033 @default.
- W4377029658 hasRelatedWork W2913223560 @default.
- W4377029658 hasRelatedWork W4235616939 @default.
- W4377029658 isParatext "false" @default.
- W4377029658 isRetracted "false" @default.
- W4377029658 workType "article" @default.