FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W578015800> ?p ?o ?g. }

• W578015800 abstract "Multiple myeloma (MM) is an incurable B-cell malignancy mainly localized to the bone marrow. Our aim was to examine the growth- and survival-promoting role of the IGF-IR and its downstream signaling components in MM cells to identify potential targets for therapy. Octreotide, a somatostatin analog that has been demonstrated to interfere with the actions of IGF-I, induced growth inhibition in both IL-6-dependent and IL-6-independent MM cell lines expressing the somatostatin receptors sst2, sst3 and sst5. Additionally, a slight pro-apoptotic effect could be observed in a few cell lines. In primary MM cells octreotide induced apoptosis, an effect that was abrogated by exogenously added IGF-I, but not by IL-6.Inhibition of IGF-I signaling in Karpas 707 cells, using either the anti-IGF-IR antibody αIR3 or the PI 3-K inhibitors LY294002 and wortmannin, increased sensitivity to apoptosis induced by dexamethasone. Exogenously added IGF-I prevented dexamethasone-induced apoptosis, an effect that could partly be mimicked by the pharmacological GSK-3β inhibitors LiCl and SB415286. Thus, we suggest the GSK-3β as an important mediator of the anti-apoptotic effects of IGF-IR signaling in MM.Using rapamycin we selectively inhibited mTOR, a phosphoprotein downstream of the IGF-IR. In MM cell lines rapamycin induced G0/G1-arrest, an effect being associated with an increase of the cyclin-dependent kinase inhibitor p27 and a decrease of the cyclins D2, D3 and E. Interestingly, in primary MM cells rapamycin induced apoptosis. Moreover, rapamycin potentiated dexamethasone-induced apoptosis, an effect that was associated with a downregulation of the anti-apoptotic protein survivin. Strikingly, the combinatorial treatment with rapamycin and dexamethasone suppressed the anti-apoptotic effects of exogenously added IGF-I and IL-6, thus suggesting this drug-combination to be active also in vivo. Two newly developed, selective IGF-I RTK inhibitors proved to be very effective in MM cell lines and in primary MM cells providing 50-90% growth inhibition within 48 h of incubation. The inhibitors induced massive apoptosis together with a prominent cell cycle arrest in the G2/M-phase. Importantly, the IGF-I RTK inhibitors downregulated the tyrosine phosphorylation of the IGF-IR β-chain but not of the insulin receptor β-chain. In conclusion, the IGF-IR potently promotes growth and survival of MM cells. Therefore, interfering with the IGF-IR signaling pathway might be a suitable strategy to improve MM treatment." @default.
• W578015800 created "2016-06-24" @default.
• W578015800 creator A5002202838 @default.
• W578015800 creator A5045152338 @default.
• W578015800 creator A5052542248 @default.
• W578015800 creator A5057873373 @default.
• W578015800 creator A5067670855 @default.
• W578015800 date "2003-01-01" @default.
• W578015800 modified "2023-09-27" @default.
• W578015800 title "Targeting the Insulin-like Growth Factor Receptor (IGF-IR) Survival Pathways in Multiple Myeloma Using Selective IGF-IR Tyrosine Kinase Inhibitors" @default.
• W578015800 hasPublicationYear "2003" @default.
• W578015800 type Work @default.
• W578015800 sameAs 578015800 @default.
• W578015800 citedByCount "0" @default.
• W578015800 crossrefType "journal-article" @default.
• W578015800 hasAuthorship W578015800A5002202838 @default.
• W578015800 hasAuthorship W578015800A5045152338 @default.
• W578015800 hasAuthorship W578015800A5052542248 @default.
• W578015800 hasAuthorship W578015800A5057873373 @default.
• W578015800 hasAuthorship W578015800A5067670855 @default.
• W578015800 hasConcept C126322002 @default.
• W578015800 hasConcept C134018914 @default.
• W578015800 hasConcept C185592680 @default.
• W578015800 hasConcept C190283241 @default.
• W578015800 hasConcept C2776912716 @default.
• W578015800 hasConcept C2778308172 @default.
• W578015800 hasConcept C502942594 @default.
• W578015800 hasConcept C55493867 @default.
• W578015800 hasConcept C62478195 @default.
• W578015800 hasConcept C71924100 @default.
• W578015800 hasConcept C86554907 @default.
• W578015800 hasConcept C86803240 @default.
• W578015800 hasConcept C95444343 @default.
• W578015800 hasConceptScore W578015800C126322002 @default.
• W578015800 hasConceptScore W578015800C134018914 @default.
• W578015800 hasConceptScore W578015800C185592680 @default.
• W578015800 hasConceptScore W578015800C190283241 @default.
• W578015800 hasConceptScore W578015800C2776912716 @default.
• W578015800 hasConceptScore W578015800C2778308172 @default.
• W578015800 hasConceptScore W578015800C502942594 @default.
• W578015800 hasConceptScore W578015800C55493867 @default.
• W578015800 hasConceptScore W578015800C62478195 @default.
• W578015800 hasConceptScore W578015800C71924100 @default.
• W578015800 hasConceptScore W578015800C86554907 @default.
• W578015800 hasConceptScore W578015800C86803240 @default.
• W578015800 hasConceptScore W578015800C95444343 @default.
• W578015800 hasLocation W5780158001 @default.
• W578015800 hasOpenAccess W578015800 @default.
• W578015800 hasPrimaryLocation W5780158001 @default.
• W578015800 hasRelatedWork W1521372172 @default.
• W578015800 hasRelatedWork W1527396907 @default.
• W578015800 hasRelatedWork W1982710936 @default.
• W578015800 hasRelatedWork W1992394857 @default.
• W578015800 hasRelatedWork W2002535735 @default.
• W578015800 hasRelatedWork W2012589659 @default.
• W578015800 hasRelatedWork W2047822416 @default.
• W578015800 hasRelatedWork W2051583323 @default.
• W578015800 hasRelatedWork W2163220531 @default.
• W578015800 hasRelatedWork W2164050810 @default.
• W578015800 hasRelatedWork W2243155356 @default.
• W578015800 hasRelatedWork W2274924671 @default.
• W578015800 hasRelatedWork W2561895577 @default.
• W578015800 hasRelatedWork W2582468125 @default.
• W578015800 hasRelatedWork W2587011361 @default.
• W578015800 hasRelatedWork W3032234624 @default.
• W578015800 hasRelatedWork W3080090838 @default.
• W578015800 hasRelatedWork W3198856605 @default.
• W578015800 hasRelatedWork W651318355 @default.
• W578015800 hasRelatedWork W2626790400 @default.
• W578015800 isParatext "false" @default.
• W578015800 isRetracted "false" @default.
• W578015800 magId "578015800" @default.
• W578015800 workType "article" @default.