FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4361945925> ?p ?o ?g. }

• W4361945925 abstract "<div>Abstract<p><b>Purpose:</b> Aberrant activation of the NF-κB transcription factors underlies the aggressive behavior and poor outcome of pancreatic ductal adenocarcinoma (PDAC). However, clinically effective and safe NF-κB inhibitors are not yet available. Because NF-κB transcription factors can be activated by the interleukin-1 receptor-associated kinases (IRAKs) downstream of the Toll-like receptors (TLRs), but has not been explored in PDAC, we sought to investigate the role of IRAKs in the pathobiology of PDAC.</p><p><b>Experimental Design:</b> We examined the phosphorylation status of IRAK4 (p-IRAK4), the master regulator of TLR signaling, in PDAC cell lines, in surgical samples and commercial tissue microarray. We then performed functional studies using small-molecule IRAK1/4 inhibitor, RNA-interference, and CRISPR/Cas9n techniques to delineate the role of IRAK4 in NF-κB activity, chemoresistance, cytokine production, and growth of PDAC cells <i>in vitro</i> and <i>in vivo</i>.</p><p><b>Results:</b> p-IRAK4 staining was detectable in the majority of PDAC lines and about 60% of human PDAC samples. The presence of p-IRAK4 strongly correlated with phospho-NF-κB/p65 staining in PDAC samples and is predictive of postoperative relapse and poor overall survival. Inhibition of IRAK4 potently reduced NF-κB activity, anchorage-independent growth, chemoresistance, and secretion of proinflammatory cytokines from PDAC cells. Both pharmacologic suppression and genetic ablation of IRAK4 greatly abolished PDAC growth in mice and augmented the therapeutic effect of gemcitabine by promoting apoptosis, reducing tumor cell proliferation and tumor fibrosis.</p><p><b>Conclusions:</b> Our data established IRAK4 as a novel therapeutic target for PDAC treatment. Development of potent IRAK4 inhibitors is needed for clinical testing. <i>Clin Cancer Res; 23(7); 1748–59. ©2016 AACR</i>.</p></div>" @default.
• W4361945925 created "2023-04-05" @default.
• W4361945925 creator A5008330168 @default.
• W4361945925 creator A5011921947 @default.
• W4361945925 creator A5026024685 @default.
• W4361945925 creator A5030541475 @default.
• W4361945925 creator A5058965019 @default.
• W4361945925 creator A5060974000 @default.
• W4361945925 creator A5064343766 @default.
• W4361945925 creator A5066901504 @default.
• W4361945925 creator A5080642100 @default.
• W4361945925 date "2023-03-31" @default.
• W4361945925 modified "2023-10-16" @default.
• W4361945925 title "Data from Constitutive IRAK4 Activation Underlies Poor Prognosis and Chemoresistance in Pancreatic Ductal Adenocarcinoma" @default.
• W4361945925 doi "https://doi.org/10.1158/1078-0432.c.6525797" @default.
• W4361945925 hasPublicationYear "2023" @default.
• W4361945925 type Work @default.
• W4361945925 citedByCount "0" @default.
• W4361945925 crossrefType "posted-content" @default.
• W4361945925 hasAuthorship W4361945925A5008330168 @default.
• W4361945925 hasAuthorship W4361945925A5011921947 @default.
• W4361945925 hasAuthorship W4361945925A5026024685 @default.
• W4361945925 hasAuthorship W4361945925A5030541475 @default.
• W4361945925 hasAuthorship W4361945925A5058965019 @default.
• W4361945925 hasAuthorship W4361945925A5060974000 @default.
• W4361945925 hasAuthorship W4361945925A5064343766 @default.
• W4361945925 hasAuthorship W4361945925A5066901504 @default.
• W4361945925 hasAuthorship W4361945925A5080642100 @default.
• W4361945925 hasBestOaLocation W43619459252 @default.
• W4361945925 hasConcept C164027704 @default.
• W4361945925 hasConcept C203014093 @default.
• W4361945925 hasConcept C2776914184 @default.
• W4361945925 hasConcept C2777730290 @default.
• W4361945925 hasConcept C2778690821 @default.
• W4361945925 hasConcept C2779730028 @default.
• W4361945925 hasConcept C502942594 @default.
• W4361945925 hasConcept C86803240 @default.
• W4361945925 hasConceptScore W4361945925C164027704 @default.
• W4361945925 hasConceptScore W4361945925C203014093 @default.
• W4361945925 hasConceptScore W4361945925C2776914184 @default.
• W4361945925 hasConceptScore W4361945925C2777730290 @default.
• W4361945925 hasConceptScore W4361945925C2778690821 @default.
• W4361945925 hasConceptScore W4361945925C2779730028 @default.
• W4361945925 hasConceptScore W4361945925C502942594 @default.
• W4361945925 hasConceptScore W4361945925C86803240 @default.
• W4361945925 hasLocation W43619459251 @default.
• W4361945925 hasLocation W43619459252 @default.
• W4361945925 hasOpenAccess W4361945925 @default.
• W4361945925 hasPrimaryLocation W43619459251 @default.
• W4361945925 hasRelatedWork W1858869890 @default.
• W4361945925 hasRelatedWork W1903606388 @default.
• W4361945925 hasRelatedWork W1993799438 @default.
• W4361945925 hasRelatedWork W2023499824 @default.
• W4361945925 hasRelatedWork W2101586744 @default.
• W4361945925 hasRelatedWork W2145676965 @default.
• W4361945925 hasRelatedWork W2150059300 @default.
• W4361945925 hasRelatedWork W2735084243 @default.
• W4361945925 hasRelatedWork W2801909890 @default.
• W4361945925 hasRelatedWork W3098059394 @default.
• W4361945925 isParatext "false" @default.
• W4361945925 isRetracted "false" @default.
• W4361945925 workType "article" @default.