FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4361819595> ?p ?o ?g. }

• W4361819595 abstract "<div>Abstract<p><b>Purpose:</b> Resistance to antiangiogenic tyrosine kinase inhibitors such as sunitinib is an important clinical problem, but its underlying mechanisms are largely unknown. We analyzed tumor sunitinib levels in mice and patients and studied sensitivity and resistance mechanisms to sunitinib.</p><p><b>Experimental Design:</b> Intratumoral and plasma sunitinib concentrations in mice and patients were determined. Sunitinib exposure on tumor cell proliferation was examined. Resistant tumor cells were derived by continuous exposure and studied for alterations in intracellular sunitinib accumulation and activity.</p><p><b>Results:</b> Intratumoral concentrations of sunitinib in mice and patients were 10.9 ± 0.5 and 9.5 ± 2.4 μmol/L, respectively, whereas plasma concentrations were 10-fold lower, 1.0 ± 0.1 and 0.3 ± 0.1 μmol/L, respectively. Sunitinib inhibited tumor cell growth at clinically relevant concentrations <i>in vitro</i>, with IC₅₀ values of 1.4 to 2.3 μmol/L. Continuous exposure to sunitinib resulted in resistance of 786-O renal and HT-29 colon cancer cells. Fluorescent microscopy revealed intracellular sunitinib distribution to acidic lysosomes, which were significantly higher expressed in resistant cells. A 1.7- to 2.5-fold higher sunitinib concentration in resistant cells was measured because of increased lysosomal sequestration. Despite the higher intracellular sunitinib accumulation, levels of the key signaling p-Akt and p-ERK 1/2 were unaffected and comparable with untreated parental cells, indicating reduced effectiveness of sunitinib.</p><p><b>Conclusion:</b> We report that sunitinib inhibits tumor cell proliferation at clinically relevant concentrations and found lysosomal sequestration to be a novel mechanism of sunitinib resistance. This finding warrants clinical evaluation whether targeting lysosomal function will overcome sunitinib resistance. <i>Clin Cancer Res; 17(23); 7337–46. ©2011 AACR</i>.</p></div>" @default.
• W4361819595 created "2023-04-05" @default.
• W4361819595 creator A5001593696 @default.
• W4361819595 creator A5003107448 @default.
• W4361819595 creator A5004518590 @default.
• W4361819595 creator A5007946879 @default.
• W4361819595 creator A5011171028 @default.
• W4361819595 creator A5011288026 @default.
• W4361819595 creator A5013852274 @default.
• W4361819595 creator A5015341987 @default.
• W4361819595 creator A5019928738 @default.
• W4361819595 creator A5020883449 @default.
• W4361819595 creator A5036871568 @default.
• W4361819595 creator A5041487312 @default.
• W4361819595 creator A5057455457 @default.
• W4361819595 creator A5080015946 @default.
• W4361819595 creator A5088673015 @default.
• W4361819595 date "2023-03-31" @default.
• W4361819595 modified "2023-09-27" @default.
• W4361819595 title "Data from Lysosomal Sequestration of Sunitinib: A Novel Mechanism of Drug Resistance" @default.
• W4361819595 doi "https://doi.org/10.1158/1078-0432.c.6519713.v1" @default.
• W4361819595 hasPublicationYear "2023" @default.
• W4361819595 type Work @default.
• W4361819595 citedByCount "0" @default.
• W4361819595 crossrefType "posted-content" @default.
• W4361819595 hasAuthorship W4361819595A5001593696 @default.
• W4361819595 hasAuthorship W4361819595A5003107448 @default.
• W4361819595 hasAuthorship W4361819595A5004518590 @default.
• W4361819595 hasAuthorship W4361819595A5007946879 @default.
• W4361819595 hasAuthorship W4361819595A5011171028 @default.
• W4361819595 hasAuthorship W4361819595A5011288026 @default.
• W4361819595 hasAuthorship W4361819595A5013852274 @default.
• W4361819595 hasAuthorship W4361819595A5015341987 @default.
• W4361819595 hasAuthorship W4361819595A5019928738 @default.
• W4361819595 hasAuthorship W4361819595A5020883449 @default.
• W4361819595 hasAuthorship W4361819595A5036871568 @default.
• W4361819595 hasAuthorship W4361819595A5041487312 @default.
• W4361819595 hasAuthorship W4361819595A5057455457 @default.
• W4361819595 hasAuthorship W4361819595A5080015946 @default.
• W4361819595 hasAuthorship W4361819595A5088673015 @default.
• W4361819595 hasConcept C121608353 @default.
• W4361819595 hasConcept C126322002 @default.
• W4361819595 hasConcept C134018914 @default.
• W4361819595 hasConcept C185592680 @default.
• W4361819595 hasConcept C202751555 @default.
• W4361819595 hasConcept C2778820342 @default.
• W4361819595 hasConcept C2779490328 @default.
• W4361819595 hasConcept C502942594 @default.
• W4361819595 hasConcept C55493867 @default.
• W4361819595 hasConcept C71924100 @default.
• W4361819595 hasConcept C79879829 @default.
• W4361819595 hasConcept C98274493 @default.
• W4361819595 hasConceptScore W4361819595C121608353 @default.
• W4361819595 hasConceptScore W4361819595C126322002 @default.
• W4361819595 hasConceptScore W4361819595C134018914 @default.
• W4361819595 hasConceptScore W4361819595C185592680 @default.
• W4361819595 hasConceptScore W4361819595C202751555 @default.
• W4361819595 hasConceptScore W4361819595C2778820342 @default.
• W4361819595 hasConceptScore W4361819595C2779490328 @default.
• W4361819595 hasConceptScore W4361819595C502942594 @default.
• W4361819595 hasConceptScore W4361819595C55493867 @default.
• W4361819595 hasConceptScore W4361819595C71924100 @default.
• W4361819595 hasConceptScore W4361819595C79879829 @default.
• W4361819595 hasConceptScore W4361819595C98274493 @default.
• W4361819595 hasLocation W43618195951 @default.
• W4361819595 hasOpenAccess W4361819595 @default.
• W4361819595 hasPrimaryLocation W43618195951 @default.
• W4361819595 hasRelatedWork W1982307539 @default.
• W4361819595 hasRelatedWork W1989862969 @default.
• W4361819595 hasRelatedWork W2027434493 @default.
• W4361819595 hasRelatedWork W2103529332 @default.
• W4361819595 hasRelatedWork W2216016299 @default.
• W4361819595 hasRelatedWork W2318852361 @default.
• W4361819595 hasRelatedWork W2991525471 @default.
• W4361819595 hasRelatedWork W3130532818 @default.
• W4361819595 hasRelatedWork W3196954506 @default.
• W4361819595 hasRelatedWork W32471882 @default.
• W4361819595 isParatext "false" @default.
• W4361819595 isRetracted "false" @default.
• W4361819595 workType "article" @default.