FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2098584395> ?p ?o ?g. }

• W2098584395 abstract "Due to the frequent dysregulation of the PI3K/AKT/mTOR signaling pathway, mTOR represents a suitable therapeutic target in hepatocellular carcinoma (HCC). However, emerging data from clinical trials of HCC patients indicate that mTOR inhibition by RAD001 (Everolimus) alone has only moderate antitumor efficacy which may be due to the feedback activation of AKT after mTOR inhibition. In this study, we analyzed the effects of dual inhibition of mTOR and AKT on the proliferation of HCC cell lines. In addition, we measured the feedback activation of each of the AKT isoforms after mTOR inhibition in HCC cell lines and their enzymatic activity in primary samples from HCC patients.The activation status of specific AKT isoforms in human HCC samples and corresponding healthy liver tissue was analyzed using an AKT isoform specific in vitro kinase assay. AKT isoform activation after mTOR inhibition was analyzed in three HCC cell lines (Hep3B, HepG2 and Huh7), and the impact of AKT signaling on proliferation after mTOR inhibition was investigated using the novel AKT inhibitor MK-2206 and AKT isoform specific knockdown cells.AKT isoforms become differentially activated during feedback activation following RAD001 treatment. The combination of mTOR inhibition and AKT isoform knockdown showed only a weak synergistic effect on proliferation of HCC cell lines. However, the combinatorial treatment with RAD001 and the pan AKT inhibitor MK-2206 resulted in a strong synergism, both in vitro and in vivo. Moreover, by analyzing primary HCC tissue samples we were able to demonstrate that a hotspot mutation (H1047R) of PI3KCA, the gene encoding the catalytic subunit of PI3K, was associated with increased in vitro kinase activity of all AKT isoforms in comparison to healthy liver tissue of the patient.Our results demonstrate that dual targeting of mTOR and AKT by use of RAD001 and the pan AKT inhibitor MK-2206 does effectively inhibit proliferation of HCC cell lines. These data suggest that combined treatment with RAD001 and MK-2206 may be a promising therapy approach in the treatment of hepatocellular carcinoma." @default.
• W2098584395 created "2016-06-24" @default.
• W2098584395 creator A5001884144 @default.
• W2098584395 creator A5037508856 @default.
• W2098584395 creator A5042541508 @default.
• W2098584395 creator A5044825904 @default.
• W2098584395 creator A5062826138 @default.
• W2098584395 creator A5084099509 @default.
• W2098584395 creator A5086135974 @default.
• W2098584395 date "2012-11-20" @default.
• W2098584395 modified "2023-10-14" @default.
• W2098584395 title "Combined targeting of AKT and mTOR synergistically inhibits proliferation of hepatocellular carcinoma cells" @default.
• W2098584395 cites W1592348719 @default.
• W2098584395 cites W1971837077 @default.
• W2098584395 cites W1975293227 @default.
• W2098584395 cites W1977267072 @default.
• W2098584395 cites W1981406217 @default.
• W2098584395 cites W1983698019 @default.
• W2098584395 cites W1990332775 @default.
• W2098584395 cites W2003832896 @default.
• W2098584395 cites W2004688803 @default.
• W2098584395 cites W2010854338 @default.
• W2098584395 cites W2011424260 @default.
• W2098584395 cites W2016211783 @default.
• W2098584395 cites W2017352677 @default.
• W2098584395 cites W2017605860 @default.
• W2098584395 cites W2023815439 @default.
• W2098584395 cites W2027114592 @default.
• W2098584395 cites W2028704745 @default.
• W2098584395 cites W2035495486 @default.
• W2098584395 cites W2035820016 @default.
• W2098584395 cites W2047073581 @default.
• W2098584395 cites W2053073281 @default.
• W2098584395 cites W2055729918 @default.
• W2098584395 cites W2057697331 @default.
• W2098584395 cites W2058544861 @default.
• W2098584395 cites W2059781917 @default.
• W2098584395 cites W2065703106 @default.
• W2098584395 cites W2069308912 @default.
• W2098584395 cites W2070841378 @default.
• W2098584395 cites W2071394735 @default.
• W2098584395 cites W2077945404 @default.
• W2098584395 cites W2086606630 @default.
• W2098584395 cites W2107813980 @default.
• W2098584395 cites W2110059026 @default.
• W2098584395 cites W2118677643 @default.
• W2098584395 cites W2126783165 @default.
• W2098584395 cites W2138424758 @default.
• W2098584395 cites W2140439371 @default.
• W2098584395 cites W2144724291 @default.
• W2098584395 cites W2144894645 @default.
• W2098584395 cites W2147264139 @default.
• W2098584395 cites W2149218373 @default.
• W2098584395 cites W2150026213 @default.
• W2098584395 cites W2155228605 @default.
• W2098584395 cites W2159714906 @default.
• W2098584395 cites W2159750196 @default.
• W2098584395 cites W2162242700 @default.
• W2098584395 cites W2163986236 @default.
• W2098584395 cites W2165901246 @default.
• W2098584395 cites W2171203591 @default.
• W2098584395 doi "https://doi.org/10.1186/1476-4598-11-85" @default.
• W2098584395 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3545733" @default.
• W2098584395 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23167739" @default.
• W2098584395 hasPublicationYear "2012" @default.
• W2098584395 type Work @default.
• W2098584395 sameAs 2098584395 @default.
• W2098584395 citedByCount "96" @default.
• W2098584395 countsByYear W20985843952013 @default.
• W2098584395 countsByYear W20985843952014 @default.
• W2098584395 countsByYear W20985843952015 @default.
• W2098584395 countsByYear W20985843952016 @default.
• W2098584395 countsByYear W20985843952017 @default.
• W2098584395 countsByYear W20985843952018 @default.
• W2098584395 countsByYear W20985843952019 @default.
• W2098584395 countsByYear W20985843952020 @default.
• W2098584395 countsByYear W20985843952021 @default.
• W2098584395 countsByYear W20985843952022 @default.
• W2098584395 countsByYear W20985843952023 @default.
• W2098584395 crossrefType "journal-article" @default.
• W2098584395 hasAuthorship W2098584395A5001884144 @default.
• W2098584395 hasAuthorship W2098584395A5037508856 @default.
• W2098584395 hasAuthorship W2098584395A5042541508 @default.
• W2098584395 hasAuthorship W2098584395A5044825904 @default.
• W2098584395 hasAuthorship W2098584395A5062826138 @default.
• W2098584395 hasAuthorship W2098584395A5084099509 @default.
• W2098584395 hasAuthorship W2098584395A5086135974 @default.
• W2098584395 hasBestOaLocation W20985843951 @default.
• W2098584395 hasConcept C104317684 @default.
• W2098584395 hasConcept C173396325 @default.
• W2098584395 hasConcept C2779699572 @default.
• W2098584395 hasConcept C43060935 @default.
• W2098584395 hasConcept C502942594 @default.
• W2098584395 hasConcept C53345823 @default.
• W2098584395 hasConcept C54355233 @default.
• W2098584395 hasConcept C55493867 @default.
• W2098584395 hasConcept C62112901 @default.
• W2098584395 hasConcept C62478195 @default.
• W2098584395 hasConcept C75217442 @default.
• W2098584395 hasConcept C81885089 @default.

• next