FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4253460675> ?p ?o ?g. }

• W4253460675 endingPage "3466" @default.
• W4253460675 startingPage "3466" @default.
• W4253460675 abstract "Abstract In multiple myeloma (MM), protein kinase C (PKC) overexpression has been reported including the prognostic adverse patient group with t (4;14) translocation. Importantly, PKC signaling pathways have been implicated in MM cell proliferation, apoptosis, and migration. Here, we investigated the novel, orally available PKC inhibitor Enzastaurin for its anti-MM activity. Enzastaurin specifically inhibits membrane, cytosolic, and nuclear phosphorylation of homologous PKC isoform residues, as well as associated kinase activity, induced by the major PKC activator TPA (Tumor-promoting phorbol ester). Consequently, it also abrogates TPA-induced phosphorylation of signaling molecules downstream of PKC including MARCKS and PKCm. In MM, Enzastaurin inhibits PKC activation triggered by growth factors and cytokines secreted by bone marrow stromal cells (BMSCs); co-stimulation with the extracellular matrix protein fibronectin, VEGF or IL-6; as well as MM patient serum. Phosphorylation of downstream signaling molecules was also abrogated, including cytoplasmic and nuclear ERK, JNK, ribosomal protein S6 and GSK3b as well as nuclear cMyc. Enzastaurin inhibits both proliferation and survival of MM cell lines and MM cells isolated from multidrug- resistant patients; as well as overcomes MM cell growth triggered by tumor cell binding to BMSCs and endothelial cells at a low micromolar range equivalent to the concentrations achieved in patient plasma during clinical trials. Importantly, synergistic cytotoxicity is observed when Enzastaurin is combined with bortezomib. Besides proliferation and survival, Enzastaurin inhibits MM cell adhesion, as well as VEGF- and IGF-1-triggered MM cell migration. It also blocks VEGF- triggered signaling pathways in endothelial cells, thereby inhibiting tubule formation. Finally and most importantly, tumor growth, survival, and angiogenesis are abrogated by Enzastaurin in an in vivo xenograft model of human MM. Our results therefore demonstrate in vitro and in vivo efficacy of the orally available PKC inhibitor Enzastaurin in MM and strongly support its clinical evaluation, alone or in combination therapies, to improve patient outcome in MM." @default.
• W4253460675 created "2022-05-12" @default.
• W4253460675 creator A5000190395 @default.
• W4253460675 creator A5006765393 @default.
• W4253460675 creator A5012186826 @default.
• W4253460675 creator A5017947172 @default.
• W4253460675 creator A5019802024 @default.
• W4253460675 creator A5023152679 @default.
• W4253460675 creator A5030002291 @default.
• W4253460675 creator A5032464400 @default.
• W4253460675 creator A5070221339 @default.
• W4253460675 creator A5073391094 @default.
• W4253460675 creator A5086388918 @default.
• W4253460675 creator A5091207345 @default.
• W4253460675 date "2006-11-16" @default.
• W4253460675 modified "2023-09-30" @default.
• W4253460675 title "Targeting PKC in Multiple Myeloma: In Vitro and In Vivo Effects of the Novel, Orally Available Small-Molecule Inhibitor Enzastaurin (LY317615.HCl)." @default.
• W4253460675 doi "https://doi.org/10.1182/blood.v108.11.3466.3466" @default.
• W4253460675 hasPublicationYear "2006" @default.
• W4253460675 type Work @default.
• W4253460675 citedByCount "0" @default.
• W4253460675 crossrefType "journal-article" @default.
• W4253460675 hasAuthorship W4253460675A5000190395 @default.
• W4253460675 hasAuthorship W4253460675A5006765393 @default.
• W4253460675 hasAuthorship W4253460675A5012186826 @default.
• W4253460675 hasAuthorship W4253460675A5017947172 @default.
• W4253460675 hasAuthorship W4253460675A5019802024 @default.
• W4253460675 hasAuthorship W4253460675A5023152679 @default.
• W4253460675 hasAuthorship W4253460675A5030002291 @default.
• W4253460675 hasAuthorship W4253460675A5032464400 @default.
• W4253460675 hasAuthorship W4253460675A5070221339 @default.
• W4253460675 hasAuthorship W4253460675A5073391094 @default.
• W4253460675 hasAuthorship W4253460675A5086388918 @default.
• W4253460675 hasAuthorship W4253460675A5091207345 @default.
• W4253460675 hasConcept C11960822 @default.
• W4253460675 hasConcept C16930146 @default.
• W4253460675 hasConcept C185592680 @default.
• W4253460675 hasConcept C195794163 @default.
• W4253460675 hasConcept C502942594 @default.
• W4253460675 hasConcept C55493867 @default.
• W4253460675 hasConcept C62112901 @default.
• W4253460675 hasConcept C62478195 @default.
• W4253460675 hasConcept C86803240 @default.
• W4253460675 hasConcept C95444343 @default.
• W4253460675 hasConceptScore W4253460675C11960822 @default.
• W4253460675 hasConceptScore W4253460675C16930146 @default.
• W4253460675 hasConceptScore W4253460675C185592680 @default.
• W4253460675 hasConceptScore W4253460675C195794163 @default.
• W4253460675 hasConceptScore W4253460675C502942594 @default.
• W4253460675 hasConceptScore W4253460675C55493867 @default.
• W4253460675 hasConceptScore W4253460675C62112901 @default.
• W4253460675 hasConceptScore W4253460675C62478195 @default.
• W4253460675 hasConceptScore W4253460675C86803240 @default.
• W4253460675 hasConceptScore W4253460675C95444343 @default.
• W4253460675 hasIssue "11" @default.
• W4253460675 hasLocation W42534606751 @default.
• W4253460675 hasOpenAccess W4253460675 @default.
• W4253460675 hasPrimaryLocation W42534606751 @default.
• W4253460675 hasRelatedWork W2000465491 @default.
• W4253460675 hasRelatedWork W2015725807 @default.
• W4253460675 hasRelatedWork W2020735591 @default.
• W4253460675 hasRelatedWork W2048746479 @default.
• W4253460675 hasRelatedWork W2106969175 @default.
• W4253460675 hasRelatedWork W2117820491 @default.
• W4253460675 hasRelatedWork W2336184425 @default.
• W4253460675 hasRelatedWork W2381340599 @default.
• W4253460675 hasRelatedWork W2384817912 @default.
• W4253460675 hasRelatedWork W3140433164 @default.
• W4253460675 hasVolume "108" @default.
• W4253460675 isParatext "false" @default.
• W4253460675 isRetracted "false" @default.
• W4253460675 workType "article" @default.