FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2727619305> ?p ?o ?g. }

• W2727619305 endingPage "91" @default.
• W2727619305 startingPage "78" @default.
• W2727619305 abstract "Oncogenic activation of phosphatidylinositol-3 kinase (PI3K) signaling plays a pivotal role in the development of glioblastoma (GBM). However, pharmacological inhibition of PI3K has so far not been therapeutically successful due to adaptive resistance through a rapid rewiring of cancer cell signaling. Here we identified that WEE1 is activated after transient exposure to PI3K inhibition and confers resistance to PI3K inhibition in GBM.Patient-derived glioma-initiating cells and established GBM cells were treated with PI3K inhibitor or WEE1 inhibitor alone or in combination, and cell proliferation was evaluated by CellTiter-Blue assay. Cell apoptosis was analyzed by TUNEL, annexin V staining, and blotting of cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase. Both subcutaneous xenograft and orthotropic xenograft studies were conducted to evaluate the effects of the combination on tumorigenesis; the tumor growth was monitored by bioluminescence imaging, and tumor tissue was analyzed by immunohistochemistry to validate signaling changes.PI3K inhibition activates WEE1 kinase, which in turn phosphorylates cell division control protein 2 homolog (Cdc2) at Tyr15 and inhibits Cdc2 activity, leading to G2/M arrest in a p53-independent manner. WEE1 inhibition abrogated the G2/M arrest and propelled cells to prematurely enter into mitosis and consequent cell death through mitotic catastrophe and apoptosis. Additionally, combination treatment significantly suppressed tumor growth in a subcutaneous model but not in an intracranial model due to limited blood-brain barrier penetration.Our findings highlight WEE1 as an adaptive resistant gene activated after PI3K inhibition, and inhibition of WEE1 potentiated the effectiveness of PI3K targeted inhibition, suggesting that a combinational inhibition of WEE1 and PI3K might allow successful targeted therapy in GBM." @default.
• W2727619305 created "2017-07-14" @default.
• W2727619305 creator A5005930092 @default.
• W2727619305 creator A5018163640 @default.
• W2727619305 creator A5025131780 @default.
• W2727619305 creator A5046338327 @default.
• W2727619305 creator A5074242312 @default.
• W2727619305 creator A5074494657 @default.
• W2727619305 creator A5074662422 @default.
• W2727619305 date "2017-07-07" @default.
• W2727619305 modified "2023-10-13" @default.
• W2727619305 title "Activation of WEE1 confers resistance to PI3K inhibition in glioblastoma" @default.
• W2727619305 cites W1500946936 @default.
• W2727619305 cites W2007920048 @default.
• W2727619305 cites W2009886463 @default.
• W2727619305 cites W2023942118 @default.
• W2727619305 cites W2025183726 @default.
• W2727619305 cites W2026425747 @default.
• W2727619305 cites W2028495676 @default.
• W2727619305 cites W2033182904 @default.
• W2727619305 cites W2035263093 @default.
• W2727619305 cites W2039442869 @default.
• W2727619305 cites W2067040565 @default.
• W2727619305 cites W2070705072 @default.
• W2727619305 cites W2071067115 @default.
• W2727619305 cites W2083259801 @default.
• W2727619305 cites W2097586379 @default.
• W2727619305 cites W2098341282 @default.
• W2727619305 cites W2102348612 @default.
• W2727619305 cites W2102839088 @default.
• W2727619305 cites W2108360575 @default.
• W2727619305 cites W2116622644 @default.
• W2727619305 cites W2120010359 @default.
• W2727619305 cites W2126718734 @default.
• W2727619305 cites W2126783165 @default.
• W2727619305 cites W2127136362 @default.
• W2727619305 cites W2138951875 @default.
• W2727619305 cites W2148636166 @default.
• W2727619305 cites W2150106850 @default.
• W2727619305 cites W2153018894 @default.
• W2727619305 cites W2155426995 @default.
• W2727619305 cites W2158402289 @default.
• W2727619305 cites W2159311956 @default.
• W2727619305 cites W2159630851 @default.
• W2727619305 cites W2164660906 @default.
• W2727619305 cites W2336817903 @default.
• W2727619305 cites W2546514099 @default.
• W2727619305 cites W4244344354 @default.
• W2727619305 doi "https://doi.org/10.1093/neuonc/nox128" @default.
• W2727619305 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5761544" @default.
• W2727619305 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29016926" @default.
• W2727619305 hasPublicationYear "2017" @default.
• W2727619305 type Work @default.
• W2727619305 sameAs 2727619305 @default.
• W2727619305 citedByCount "22" @default.
• W2727619305 countsByYear W27276193052018 @default.
• W2727619305 countsByYear W27276193052019 @default.
• W2727619305 countsByYear W27276193052020 @default.
• W2727619305 countsByYear W27276193052021 @default.
• W2727619305 countsByYear W27276193052022 @default.
• W2727619305 countsByYear W27276193052023 @default.
• W2727619305 crossrefType "journal-article" @default.
• W2727619305 hasAuthorship W2727619305A5005930092 @default.
• W2727619305 hasAuthorship W2727619305A5018163640 @default.
• W2727619305 hasAuthorship W2727619305A5025131780 @default.
• W2727619305 hasAuthorship W2727619305A5046338327 @default.
• W2727619305 hasAuthorship W2727619305A5074242312 @default.
• W2727619305 hasAuthorship W2727619305A5074494657 @default.
• W2727619305 hasAuthorship W2727619305A5074662422 @default.
• W2727619305 hasBestOaLocation W27276193051 @default.
• W2727619305 hasConcept C120504264 @default.
• W2727619305 hasConcept C190283241 @default.
• W2727619305 hasConcept C2781252693 @default.
• W2727619305 hasConcept C29537977 @default.
• W2727619305 hasConcept C31573885 @default.
• W2727619305 hasConcept C502942594 @default.
• W2727619305 hasConcept C55493867 @default.
• W2727619305 hasConcept C62112901 @default.
• W2727619305 hasConcept C62478195 @default.
• W2727619305 hasConcept C86554907 @default.
• W2727619305 hasConcept C86803240 @default.
• W2727619305 hasConcept C93304396 @default.
• W2727619305 hasConcept C95444343 @default.
• W2727619305 hasConceptScore W2727619305C120504264 @default.
• W2727619305 hasConceptScore W2727619305C190283241 @default.
• W2727619305 hasConceptScore W2727619305C2781252693 @default.
• W2727619305 hasConceptScore W2727619305C29537977 @default.
• W2727619305 hasConceptScore W2727619305C31573885 @default.
• W2727619305 hasConceptScore W2727619305C502942594 @default.
• W2727619305 hasConceptScore W2727619305C55493867 @default.
• W2727619305 hasConceptScore W2727619305C62112901 @default.
• W2727619305 hasConceptScore W2727619305C62478195 @default.
• W2727619305 hasConceptScore W2727619305C86554907 @default.
• W2727619305 hasConceptScore W2727619305C86803240 @default.
• W2727619305 hasConceptScore W2727619305C93304396 @default.
• W2727619305 hasConceptScore W2727619305C95444343 @default.
• W2727619305 hasFunder F4320306777 @default.
• W2727619305 hasIssue "1" @default.

• next