Matches in SemOpenAlex for { <https://semopenalex.org/work/W2086074262> ?p ?o ?g. }
Showing items 1 to 90 of
90
with 100 items per page.
- W2086074262 abstract "Tumor blood vessels are distinctly abnormal in structure and function. When compared to normal vessels, they are enlarged, tortuous, leaky, poorly covered by pericytes and with a defective basement membrane. VEGF is a prominent cytokine responsible for the hyperpermeable state of tumor microvasculature to plasma macromolecules. The phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway functions downstream of VEGF and can activate the production of the free radical gas nitric oxide (NO) through the enzyme endothelial NO synthase (eNOS), a key player for the in vivo biological activity of VEGF. In the present study, we investigated the effect of NVP-BYL719, a novel, synthetic low molecular mass compound, which potently and selectively inhibits class I PI3K isoform alpha activity, on vascular leakage in tumors and its impact on tumor progression in an orthotopic breast cancer model (BN472) in syngeneic rats. Effects on the vasculature were investigated in normal and tumor tissues via tumor interstitial fluid pressure (IFP) measurements in conscious animals via radio-telemetry and a modified Miles assay. The antiangiogenic effect of NVP-BYL719 and its impact on tumor progression was also assessed in an U87MG glioblastoma subcutaneous xenograft tumor model. Pathway inhibition was confirmed using tumor histology and Reverse Phase Protein Array (RPPA) approaches. NVP-BYL719 inhibits VEGF driven tissue formation as well as neo-vascularization of the newly formed tissue. Moreover, the compound strongly inhibited microvessel permeability in normal tissue as determined in the modified miles assay. Similarly, tumor interstitial fluid pressure (IFP), a phenomenon that is directly dependent on tumor vessel permeability, was significantly reduced (up to 43%) by NVP-BYL719 in a dose-dependent manner, upon oral administration in BN472 mammary carcinoma grown orthotopically in syngeneic rats. Concomitantly, tumor growth was significantly inhibited in BN472 mammary carcinoma and U87MG xenografts. The compound was well tolerated with no significant body weight loss at any tested dose. In conclusion, our data suggest that NVP-BYL719, a Class I PI3K selective inhibitor of p110 alpha, interferes with the tumor vasculature system. Thus, the anti-angiogenic proprieties of NVP-BYL719 might participate to the antitumor activity (or efficacy) of the compound. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3743. doi:1538-7445.AM2012-3743" @default.
- W2086074262 created "2016-06-24" @default.
- W2086074262 creator A5004338973 @default.
- W2086074262 creator A5006668214 @default.
- W2086074262 creator A5009403375 @default.
- W2086074262 creator A5010136394 @default.
- W2086074262 creator A5020617247 @default.
- W2086074262 creator A5022308157 @default.
- W2086074262 creator A5044326792 @default.
- W2086074262 creator A5086893977 @default.
- W2086074262 creator A5089863595 @default.
- W2086074262 date "2012-04-15" @default.
- W2086074262 modified "2023-10-18" @default.
- W2086074262 title "Abstract 3743: NVP-BYL719, a selective inhibitor of the class Ia PI3K isoform alpha impairs angiogenesis and microvascular permeability." @default.
- W2086074262 doi "https://doi.org/10.1158/1538-7445.am2012-3743" @default.
- W2086074262 hasPublicationYear "2012" @default.
- W2086074262 type Work @default.
- W2086074262 sameAs 2086074262 @default.
- W2086074262 citedByCount "0" @default.
- W2086074262 crossrefType "proceedings-article" @default.
- W2086074262 hasAuthorship W2086074262A5004338973 @default.
- W2086074262 hasAuthorship W2086074262A5006668214 @default.
- W2086074262 hasAuthorship W2086074262A5009403375 @default.
- W2086074262 hasAuthorship W2086074262A5010136394 @default.
- W2086074262 hasAuthorship W2086074262A5020617247 @default.
- W2086074262 hasAuthorship W2086074262A5022308157 @default.
- W2086074262 hasAuthorship W2086074262A5044326792 @default.
- W2086074262 hasAuthorship W2086074262A5086893977 @default.
- W2086074262 hasAuthorship W2086074262A5089863595 @default.
- W2086074262 hasConcept C113045295 @default.
- W2086074262 hasConcept C121608353 @default.
- W2086074262 hasConcept C126322002 @default.
- W2086074262 hasConcept C142724271 @default.
- W2086074262 hasConcept C150903083 @default.
- W2086074262 hasConcept C185592680 @default.
- W2086074262 hasConcept C207001950 @default.
- W2086074262 hasConcept C2776107976 @default.
- W2086074262 hasConcept C2776436680 @default.
- W2086074262 hasConcept C2780394083 @default.
- W2086074262 hasConcept C502942594 @default.
- W2086074262 hasConcept C55493867 @default.
- W2086074262 hasConcept C62478195 @default.
- W2086074262 hasConcept C71924100 @default.
- W2086074262 hasConcept C75217442 @default.
- W2086074262 hasConcept C86554907 @default.
- W2086074262 hasConcept C86803240 @default.
- W2086074262 hasConceptScore W2086074262C113045295 @default.
- W2086074262 hasConceptScore W2086074262C121608353 @default.
- W2086074262 hasConceptScore W2086074262C126322002 @default.
- W2086074262 hasConceptScore W2086074262C142724271 @default.
- W2086074262 hasConceptScore W2086074262C150903083 @default.
- W2086074262 hasConceptScore W2086074262C185592680 @default.
- W2086074262 hasConceptScore W2086074262C207001950 @default.
- W2086074262 hasConceptScore W2086074262C2776107976 @default.
- W2086074262 hasConceptScore W2086074262C2776436680 @default.
- W2086074262 hasConceptScore W2086074262C2780394083 @default.
- W2086074262 hasConceptScore W2086074262C502942594 @default.
- W2086074262 hasConceptScore W2086074262C55493867 @default.
- W2086074262 hasConceptScore W2086074262C62478195 @default.
- W2086074262 hasConceptScore W2086074262C71924100 @default.
- W2086074262 hasConceptScore W2086074262C75217442 @default.
- W2086074262 hasConceptScore W2086074262C86554907 @default.
- W2086074262 hasConceptScore W2086074262C86803240 @default.
- W2086074262 hasLocation W20860742621 @default.
- W2086074262 hasOpenAccess W2086074262 @default.
- W2086074262 hasPrimaryLocation W20860742621 @default.
- W2086074262 hasRelatedWork W1965710598 @default.
- W2086074262 hasRelatedWork W1975427881 @default.
- W2086074262 hasRelatedWork W1986206057 @default.
- W2086074262 hasRelatedWork W1990095055 @default.
- W2086074262 hasRelatedWork W1994437330 @default.
- W2086074262 hasRelatedWork W1996319994 @default.
- W2086074262 hasRelatedWork W2009289648 @default.
- W2086074262 hasRelatedWork W2010526464 @default.
- W2086074262 hasRelatedWork W2086841409 @default.
- W2086074262 hasRelatedWork W2092768795 @default.
- W2086074262 hasRelatedWork W2127931911 @default.
- W2086074262 hasRelatedWork W2142906517 @default.
- W2086074262 hasRelatedWork W2148140793 @default.
- W2086074262 hasRelatedWork W2150497617 @default.
- W2086074262 hasRelatedWork W2151619877 @default.
- W2086074262 hasRelatedWork W2331669180 @default.
- W2086074262 hasRelatedWork W2337269035 @default.
- W2086074262 hasRelatedWork W2467780838 @default.
- W2086074262 hasRelatedWork W3081931373 @default.
- W2086074262 hasRelatedWork W2798900444 @default.
- W2086074262 isParatext "false" @default.
- W2086074262 isRetracted "false" @default.
- W2086074262 magId "2086074262" @default.
- W2086074262 workType "article" @default.