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dc.contributor.authorJubb, AMen
dc.contributor.authorTurley, Hen
dc.contributor.authorMoeller, HCen
dc.contributor.authorSteers, Gen
dc.contributor.authorHan, Cen
dc.contributor.authorLi, J-Len
dc.contributor.authorLeek, Ren
dc.contributor.authorTan, EYen
dc.contributor.authorSingh, Ben
dc.contributor.authorMortensen, NJen
dc.contributor.authorNoguera-Troise, Ien
dc.contributor.authorPezzella, Fen
dc.contributor.authorGatter, KCen
dc.contributor.authorThurston, Gen
dc.contributor.authorFox, SBen
dc.contributor.authorHarris, ALen
dc.date.accessioned2017-11-27T16:41:32Z
dc.date.available2017-11-27T16:41:32Z
dc.date.issued2009-11-17en
dc.identifier.urihttp://hdl.handle.net/10026.1/10309
dc.description.abstract

BACKGROUND: Delta-like ligand 4 (Dll4) is a Notch ligand that is upregulated by hypoxia and vascular endothelial growth factor-A (VEGF-A) and is reported to have a role in tumor angiogenesis. Evidence from xenograft studies suggests that inhibiting Dll4-Notch signalling may overcome resistance to anti-VEGF therapy. The aim of this study was to characterise the expression of Dll4 in colon cancer and to assess whether it is associated with markers of hypoxia and prognosis. METHOD: In all, 177 colon cancers were represented in tissue microarrays. Immunohistochemistry was performed using validated antibodies against Dll4, VEGF, hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, prolyl hydroxylase (PHD)1, PHD2, PHD3 and carbonic anhydrase 9 (CA9). RESULTS: The expression of Dll4 was observed preferentially in the endothelium of 71% (125 out of 175) of colon cancers, but not in the endothelium adjacent to normal mucosa (none out of 107, P<0.0001). The expression of VEGF was significantly associated with HIF-2alpha (P<0.0001) and Dll4 (P=0.010). Only HIF-2alpha had a significant multivariate prognostic effect (hazard ratio 1.61, 95% confidence interval 1.01-2.57). Delta-like ligand 4 was also expressed by neoplastic cells, particularly neoplastic goblet cells. CONCLUSION: Endothelial expression of Dll4 is not a prognostic factor, but is significantly associated with VEGF. Assessing endothelial Dll4 expression may be critical in predicting response to anti-VEGF therapies.

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dc.format.extent1749 - 1757en
dc.languageengen
dc.language.isoengen
dc.subjectAdolescenten
dc.subjectAdulten
dc.subjectAgeden
dc.subjectAged, 80 and overen
dc.subjectBasic Helix-Loop-Helix Transcription Factorsen
dc.subjectBiomarkers, Tumoren
dc.subjectCell Hypoxiaen
dc.subjectColonic Neoplasmsen
dc.subjectEndothelial Cellsen
dc.subjectFemaleen
dc.subjectGoblet Cellsen
dc.subjectHumansen
dc.subjectImmunohistochemistryen
dc.subjectIntercellular Signaling Peptides and Proteinsen
dc.subjectMaleen
dc.subjectMiddle Ageden
dc.subjectNeovascularization, Pathologicen
dc.subjectPrognosisen
dc.subjectSurvival Rateen
dc.subjectVascular Endothelial Growth Factor Aen
dc.subjectYoung Adulten
dc.titleExpression of delta-like ligand 4 (Dll4) and markers of hypoxia in colon cancer.en
dc.typeJournal Article
plymouth.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/19844231en
plymouth.issue10en
plymouth.volume101en
plymouth.publication-statusPublisheden
plymouth.journalBr J Canceren
dc.identifier.doi10.1038/sj.bjc.6605368en
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine/UoA01 Clinical Medicine
dc.publisher.placeEnglanden
dc.identifier.eissn1532-1827en
dc.rights.embargoperiodNot knownen
rioxxterms.versionofrecord10.1038/sj.bjc.6605368en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.typeJournal Article/Reviewen


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