<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">A Drouillard</style></author><author><style face="normal" font="default" size="100%">F Puleo</style></author><author><style face="normal" font="default" size="100%">J B Bachet</style></author><author><style face="normal" font="default" size="100%">S Ouazzani</style></author><author><style face="normal" font="default" size="100%">Annabelle Calomme</style></author><author><style face="normal" font="default" size="100%">P Demetter</style></author><author><style face="normal" font="default" size="100%">G Verset</style></author><author><style face="normal" font="default" size="100%">J L Van Laethem</style></author><author><style face="normal" font="default" size="100%">R Maréchal</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">DLL4 expression is a prognostic marker and may predict gemcitabine benefit in resected pancreatic cancer.</style></title><secondary-title><style face="normal" font="default" size="100%">Br J Cancer</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adaptor Proteins, Signal Transducing</style></keyword><keyword><style  face="normal" font="default" size="100%">Adenocarcinoma</style></keyword><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Aged, 80 and over</style></keyword><keyword><style  face="normal" font="default" size="100%">Antimetabolites, Antineoplastic</style></keyword><keyword><style  face="normal" font="default" size="100%">Biomarkers, Tumor</style></keyword><keyword><style  face="normal" font="default" size="100%">Calcium-Binding Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Carcinoma, Pancreatic Ductal</style></keyword><keyword><style  face="normal" font="default" size="100%">Chemotherapy, Adjuvant</style></keyword><keyword><style  face="normal" font="default" size="100%">Deoxycytidine</style></keyword><keyword><style  face="normal" font="default" size="100%">Disease-Free Survival</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">immunohistochemistry</style></keyword><keyword><style  face="normal" font="default" size="100%">Intercellular Signaling Peptides and Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Kaplan-Meier Estimate</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">middle aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Multivariate Analysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Pancreatic Neoplasms</style></keyword><keyword><style  face="normal" font="default" size="100%">Prognosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptor, Notch1</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptor, Notch3</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2016</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2016 Nov 08</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">115</style></volume><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;There is an increasing interest for Notch signalling pathway and particularly Delta-like ligand 4 (DLL4) as potential therapeutic target to improve outcome for patients with pancreatic ductal adenocarcinoma (PDAC).&lt;/p&gt;

&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;Using immunohistochemistry (IHC) and tissue microarray (TMA), we assessed the expression patterns of DLL4, Notch1 and Notch3 in 151 patients from two independent cohorts of resected PDAC. We investigated the prognostic and the predictive significance of these proteins.&lt;/p&gt;

&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;High IHC DLL4 expression in cancer cells was associated with worse overall survival (OS) and disease-free survival (DFS) than low DLL4 expression (median OS: 12.9 vs 30.4 months, P=0.004 and median DFS: 8.8 vs 17.4 months, P=0.02). High DLL4 expression remained a significant negative prognostic factor in multivariate analysis (HR for OS: 2.1, P=0.02 and HR for DFS: 2.0, P=0.02). Low DLL4 abundance was associated with a longer OS-only for patients who received an adjuvant gemcitabine-based chemotherapy (P&amp;lt;0.001) but not for patients who did not receive gemcitabine (P=0.72). Furthermore, the interaction test for adjuvant gemcitabine therapy was statistically significant (P&amp;lt;0.001). The validating cohort recapitulated the findings of the training cohort.&lt;/p&gt;

&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;Low DLL4 abundance in tumour cells may predict the benefit from adjuvant gemcitabine therapy after PDAC resection.&lt;/p&gt;
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