FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2895445516> ?p ?o ?g. }

• W2895445516 endingPage "1745" @default.
• W2895445516 startingPage "1735" @default.
• W2895445516 abstract "Glioblastoma multiforme (GBM) has a poor prognosis with an overall survival of 14–15 months after surgery, radiation and chemotherapy using temozolomide (TMZ). A major problem is that the tumors acquire resistance to therapy. In an effort to improve the therapeutic efficacy of TMZ, we performed a genome‐wide RNA interference (RNAi) synthetic lethality screen to establish a functional gene signature for TMZ sensitivity in human GBM cells. We then queried the Connectivity Map database to search for drugs that would induce corresponding changes in gene expression. By this approach we identified several potential pharmacological sensitizers to TMZ, where the most potent drug was the established antipsychotic agent Thioridazine, which significantly improved TMZ sensitivity while not demonstrating any significant toxicity alone. Mechanistically, we show that the specific chemosensitizing effect of Thioridazine is mediated by impairing autophagy, thereby preventing adaptive metabolic alterations associated with TMZ resistance. Moreover, we demonstrate that Thioridazine inhibits late‐stage autophagy by impairing fusion between autophagosomes and lysosomes. Finally, Thioridazine in combination with TMZ significantly inhibits brain tumor growth in vivo , demonstrating the potential clinical benefits of compounds targeting the autophagy‐lysosome pathway. Our study emphasizes the feasibility of exploiting drug repurposing for the design of novel therapeutic strategies for GBM." @default.
• W2895445516 created "2018-10-12" @default.
• W2895445516 creator A5005495166 @default.
• W2895445516 creator A5008528112 @default.
• W2895445516 creator A5024269446 @default.
• W2895445516 creator A5032764121 @default.
• W2895445516 creator A5041043163 @default.
• W2895445516 creator A5052389840 @default.
• W2895445516 creator A5056068760 @default.
• W2895445516 creator A5062812619 @default.
• W2895445516 creator A5065173224 @default.
• W2895445516 creator A5065959481 @default.
• W2895445516 creator A5066218031 @default.
• W2895445516 creator A5066633544 @default.
• W2895445516 creator A5068186967 @default.
• W2895445516 creator A5069543439 @default.
• W2895445516 creator A5073036493 @default.
• W2895445516 creator A5077636380 @default.
• W2895445516 creator A5084014841 @default.
• W2895445516 creator A5088710844 @default.
• W2895445516 creator A5089792780 @default.
• W2895445516 creator A5091343254 @default.
• W2895445516 date "2018-12-11" @default.
• W2895445516 modified "2023-10-17" @default.
• W2895445516 title "Thioridazine inhibits autophagy and sensitizes glioblastoma cells to temozolomide" @default.
• W2895445516 cites W1544776535 @default.
• W2895445516 cites W1678795445 @default.
• W2895445516 cites W1966912910 @default.
• W2895445516 cites W1971495943 @default.
• W2895445516 cites W1980889025 @default.
• W2895445516 cites W1988110756 @default.
• W2895445516 cites W1995919174 @default.
• W2895445516 cites W2012065284 @default.
• W2895445516 cites W2029980980 @default.
• W2895445516 cites W2039014242 @default.
• W2895445516 cites W2044580929 @default.
• W2895445516 cites W2051682623 @default.
• W2895445516 cites W2059624809 @default.
• W2895445516 cites W2063704076 @default.
• W2895445516 cites W2065628422 @default.
• W2895445516 cites W2096287682 @default.
• W2895445516 cites W2101228747 @default.
• W2895445516 cites W2102690338 @default.
• W2895445516 cites W2104072199 @default.
• W2895445516 cites W2104697581 @default.
• W2895445516 cites W2105981681 @default.
• W2895445516 cites W2106255061 @default.
• W2895445516 cites W2107223831 @default.
• W2895445516 cites W2115886998 @default.
• W2895445516 cites W2117769306 @default.
• W2895445516 cites W2120134578 @default.
• W2895445516 cites W2120872266 @default.
• W2895445516 cites W2121604817 @default.
• W2895445516 cites W2126968146 @default.
• W2895445516 cites W2133000461 @default.
• W2895445516 cites W2142845200 @default.
• W2895445516 cites W2152007057 @default.
• W2895445516 doi "https://doi.org/10.1002/ijc.31912" @default.
• W2895445516 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30289977" @default.
• W2895445516 hasPublicationYear "2018" @default.
• W2895445516 type Work @default.
• W2895445516 sameAs 2895445516 @default.
• W2895445516 citedByCount "52" @default.
• W2895445516 countsByYear W28954455162019 @default.
• W2895445516 countsByYear W28954455162020 @default.
• W2895445516 countsByYear W28954455162021 @default.
• W2895445516 countsByYear W28954455162022 @default.
• W2895445516 countsByYear W28954455162023 @default.
• W2895445516 crossrefType "journal-article" @default.
• W2895445516 hasAuthorship W2895445516A5005495166 @default.
• W2895445516 hasAuthorship W2895445516A5008528112 @default.
• W2895445516 hasAuthorship W2895445516A5024269446 @default.
• W2895445516 hasAuthorship W2895445516A5032764121 @default.
• W2895445516 hasAuthorship W2895445516A5041043163 @default.
• W2895445516 hasAuthorship W2895445516A5052389840 @default.
• W2895445516 hasAuthorship W2895445516A5056068760 @default.
• W2895445516 hasAuthorship W2895445516A5062812619 @default.
• W2895445516 hasAuthorship W2895445516A5065173224 @default.
• W2895445516 hasAuthorship W2895445516A5065959481 @default.
• W2895445516 hasAuthorship W2895445516A5066218031 @default.
• W2895445516 hasAuthorship W2895445516A5066633544 @default.
• W2895445516 hasAuthorship W2895445516A5068186967 @default.
• W2895445516 hasAuthorship W2895445516A5069543439 @default.
• W2895445516 hasAuthorship W2895445516A5073036493 @default.
• W2895445516 hasAuthorship W2895445516A5077636380 @default.
• W2895445516 hasAuthorship W2895445516A5084014841 @default.
• W2895445516 hasAuthorship W2895445516A5088710844 @default.
• W2895445516 hasAuthorship W2895445516A5089792780 @default.
• W2895445516 hasAuthorship W2895445516A5091343254 @default.
• W2895445516 hasBestOaLocation W28954455161 @default.
• W2895445516 hasConcept C104317684 @default.
• W2895445516 hasConcept C134935766 @default.
• W2895445516 hasConcept C166703698 @default.
• W2895445516 hasConcept C190283241 @default.
• W2895445516 hasConcept C203522944 @default.
• W2895445516 hasConcept C2777389519 @default.
• W2895445516 hasConcept C2778227246 @default.
• W2895445516 hasConcept C2778502085 @default.

• next