FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2096009033> ?p ?o ?g. }

• W2096009033 endingPage "6039" @default.
• W2096009033 startingPage "6029" @default.
• W2096009033 abstract "Abstract Purpose: Melanoma is relatively resistant to chemotherapy; improved targeting of molecules critical for cell proliferation and survival are needed. Phosphatidylinositol-3 kinase (PI3K) is an important target in melanoma; however, activity of PI3K inhibitors (PI3KI) is limited. Our purpose was to assess mTOR as a cotarget for PI3K. Methods: Using a method of quantitative immunofluorescence to measure mTOR expression in a large melanoma cohort, we studied associations with PI3K subunits, p85 and p110α. We assessed addition of the mTOR inhibitor rapamycin to 2 PI3KIs, NVP-BKM120 and LY294002. We studied in vitro activity of a novel dual PI3K/mTOR inhibitor NVP-BEZ235 and activity of the combination of NVP-BEZ235 and the MAP/ERK kinase (MEK) inhibitor AZD6244. Results: Strong coexpression of mTOR and p110α was observed (ρ = 0.658; P &lt; 0.0001). Less coexpression was seen with p85 (ρ = 0.239; P &lt; 0.0001). Strong synergism was shown between rapamycin and both PI3KIs. Activity of both PI3KIs was similarly enhanced with all rapamycin concentrations used. The dual PI3K/mTOR inhibitor effectively inhibited viability in 23 melanoma cell lines (IC50 values in the nanomolar range), regardless of B-Raf mutation status, with resultant reduction in clonogenicity and downregulation of pAkt and pP70S6K. Synergism was seen when combining NVP-BEZ235 and AZD6244, with resultant increases in poly(ADP-ribose) polymerase and caspase-2 cleavage. Conclusions: mTOR and p110α are coexpressed in melanoma. Rapamycin concentrations as low as 1 nmol/L enhance activity of PI3KIs. The dual PI3K/mTOR inhibitor NVP-BEZ235 is highly active in melanoma cells in vitro, suggesting that concurrent PI3K and mTOR targeting in melanoma warrants further investigation, both alone and in combination with MEK inhibitors." @default.
• W2096009033 created "2016-06-24" @default.
• W2096009033 creator A5001175430 @default.
• W2096009033 creator A5013767340 @default.
• W2096009033 creator A5025447613 @default.
• W2096009033 creator A5027326018 @default.
• W2096009033 creator A5029775131 @default.
• W2096009033 creator A5057160792 @default.
• W2096009033 creator A5067591137 @default.
• W2096009033 date "2010-12-15" @default.
• W2096009033 modified "2023-09-26" @default.
• W2096009033 title "Vertical Targeting of the Phosphatidylinositol-3 Kinase Pathway as a Strategy for Treating Melanoma" @default.
• W2096009033 cites W1979782687 @default.
• W2096009033 cites W1988620734 @default.
• W2096009033 cites W1991394829 @default.
• W2096009033 cites W1994376203 @default.
• W2096009033 cites W2004691500 @default.
• W2096009033 cites W2009886463 @default.
• W2096009033 cites W2013036515 @default.
• W2096009033 cites W2014096417 @default.
• W2096009033 cites W2016514257 @default.
• W2096009033 cites W2017563355 @default.
• W2096009033 cites W2019349725 @default.
• W2096009033 cites W2019809220 @default.
• W2096009033 cites W2022848869 @default.
• W2096009033 cites W2039628288 @default.
• W2096009033 cites W2056891806 @default.
• W2096009033 cites W2060809474 @default.
• W2096009033 cites W2066179587 @default.
• W2096009033 cites W2067667773 @default.
• W2096009033 cites W2071285300 @default.
• W2096009033 cites W2077230170 @default.
• W2096009033 cites W2077945404 @default.
• W2096009033 cites W2086409166 @default.
• W2096009033 cites W2087012714 @default.
• W2096009033 cites W2087861588 @default.
• W2096009033 cites W2094079572 @default.
• W2096009033 cites W2100158834 @default.
• W2096009033 cites W2101995865 @default.
• W2096009033 cites W2104381422 @default.
• W2096009033 cites W2107218721 @default.
• W2096009033 cites W2108307140 @default.
• W2096009033 cites W2119886330 @default.
• W2096009033 cites W2124727390 @default.
• W2096009033 cites W2129318139 @default.
• W2096009033 cites W2141417189 @default.
• W2096009033 cites W2142528126 @default.
• W2096009033 cites W2143945587 @default.
• W2096009033 cites W2151258296 @default.
• W2096009033 cites W2152606604 @default.
• W2096009033 cites W2155009617 @default.
• W2096009033 cites W2155459097 @default.
• W2096009033 cites W2156266404 @default.
• W2096009033 cites W2159530979 @default.
• W2096009033 cites W2163188200 @default.
• W2096009033 cites W2171095731 @default.
• W2096009033 cites W2413151491 @default.
• W2096009033 cites W2528718143 @default.
• W2096009033 doi "https://doi.org/10.1158/1078-0432.ccr-10-1490" @default.
• W2096009033 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3058635" @default.
• W2096009033 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21169255" @default.
• W2096009033 hasPublicationYear "2010" @default.
• W2096009033 type Work @default.
• W2096009033 sameAs 2096009033 @default.
• W2096009033 citedByCount "71" @default.
• W2096009033 countsByYear W20960090332012 @default.
• W2096009033 countsByYear W20960090332013 @default.
• W2096009033 countsByYear W20960090332014 @default.
• W2096009033 countsByYear W20960090332015 @default.
• W2096009033 countsByYear W20960090332016 @default.
• W2096009033 countsByYear W20960090332017 @default.
• W2096009033 countsByYear W20960090332018 @default.
• W2096009033 countsByYear W20960090332019 @default.
• W2096009033 countsByYear W20960090332020 @default.
• W2096009033 countsByYear W20960090332022 @default.
• W2096009033 countsByYear W20960090332023 @default.
• W2096009033 crossrefType "journal-article" @default.
• W2096009033 hasAuthorship W2096009033A5001175430 @default.
• W2096009033 hasAuthorship W2096009033A5013767340 @default.
• W2096009033 hasAuthorship W2096009033A5025447613 @default.
• W2096009033 hasAuthorship W2096009033A5027326018 @default.
• W2096009033 hasAuthorship W2096009033A5029775131 @default.
• W2096009033 hasAuthorship W2096009033A5057160792 @default.
• W2096009033 hasAuthorship W2096009033A5067591137 @default.
• W2096009033 hasBestOaLocation W20960090331 @default.
• W2096009033 hasConcept C184235292 @default.
• W2096009033 hasConcept C185592680 @default.
• W2096009033 hasConcept C190283241 @default.
• W2096009033 hasConcept C2776912716 @default.
• W2096009033 hasConcept C2777658100 @default.
• W2096009033 hasConcept C2780610907 @default.
• W2096009033 hasConcept C2781465904 @default.
• W2096009033 hasConcept C502942594 @default.
• W2096009033 hasConcept C53227056 @default.
• W2096009033 hasConcept C55493867 @default.
• W2096009033 hasConcept C57074206 @default.
• W2096009033 hasConcept C62112901 @default.
• W2096009033 hasConcept C86554907 @default.

• next