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• W2013851393 abstract "You have accessJournal of UrologyKidney Cancer: Advanced II1 Apr 20101796 PREDICTION FOR AND MECHANISM OF RESPONSE TO DENDRITIC CELL (DC)-BASED IMMUNOTHERAPY IN METASTATIC RENAL CELL CARCINOMA (RCC)– GENE EXPRESSION PROFILING OF PERIPHERAL BLOOD LYMPHOCYTES (PBL) Thomas Schwaab, Thomas Hampton, Benita Wolf, Adrian Schwarzer, Jiang Gui, Jan Fisher, John Seigne, and Marc Ernstoff Thomas SchwaabThomas Schwaab Buffalo, NY More articles by this author , Thomas HamptonThomas Hampton Lebanon, NH More articles by this author , Benita WolfBenita Wolf Hannover, Germany More articles by this author , Adrian SchwarzerAdrian Schwarzer Hannover, Germany More articles by this author , Jiang GuiJiang Gui Lebanon, NH More articles by this author , Jan FisherJan Fisher Lebanon, NH More articles by this author , John SeigneJohn Seigne Lebanon, NH More articles by this author , and Marc ErnstoffMarc Ernstoff Lebanon, NH More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1720AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We recently reported a 50% overall response rate and significant immunologic effects in a Phase II trial of DC-based immunotherapy. This study analyzes predictors and pathways of response using gene expression profiling of PBL in these patients. METHODS 18 patients with metastatic RCC were enrolled. 9 healthy age-matched donors were used as controls (HD). PBL were isolated from leukapheresis product prior to treatment and after the induction cycle. We hybridized RNA to Affymetrix Human Gene 1.0 ST arrays and obtained normalized expression values from Expression Console, initially selecting genes with a fold change greater than 2 (up or down) and a p < .05. We performed Ingenuity Pathway Analysis (IPA) on gene sets based on 1) HD vs RCC 2) treatment effect in patients and 3) differences between responders and non responders. We interrogated the expression behavior of genes belonging to paths found significant by IPA by hierarchical clustering, and identified a consolidated set of genes that belonged to several paths. RESULTS Patients were categorized as responders (R, 3 complete, 6 partial) and non-responders (NR, 4 stable, 5 progressive). Comparing R to all RCC patients, 56 genes of interest were identified and included surface receptors, cell signaling, activation and apoptosis pathways. The vast majority of these genes were up-regulated in RCC compared to HD. Only IL-6, IFN-α, SMAD7, CD40, DEFB1 and CxCL5 were down-regulated (Fold Change (FC) -0.14 to -0.18, p=0.03 to 0.07). Responders showed down-regulation of most genes pre- treatment. However, IL-6, IFN-α and SMAD7 showed significant up-regulation pre-treatment (FC 0.352, p=0.018; FC 0.307, p=0.039; FC 0.399, p=0.032, respectively). To implicate mechanisms of response, 26 genes of interest were identified in an analysis of R compared to NR. No distinct pattern of up- or down regulation was obvious in RCC when compared to HD (17 up- and 9 down-regulated). IL-8, IL-1B, TRAF6 and STAT3 were identified as the genes with the most interactions to other genes. These 4 genes were not preferentially expressed pre-treatment (FC -0.026,p=0.09; FC-0.328,p=0.053; FC0.221, p=0.02, FC-0.309, p=0.0017), but showed a significant up-regulation after treatment (IL-8: FC0.481,p=0.003; IL1B: FC0.861,p=0.00062; TRAF6: FC0.315,p=0.02; STAT3: FC0.078,p=0.062). CONCLUSIONS This study implicates the expression of IL-6, IFN-α and SMAD7 as predictors for response and IL-8, IL-1B, TRAF6 and STAT3 pathways as mechanisms for response. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e697 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Thomas Schwaab Buffalo, NY More articles by this author Thomas Hampton Lebanon, NH More articles by this author Benita Wolf Hannover, Germany More articles by this author Adrian Schwarzer Hannover, Germany More articles by this author Jiang Gui Lebanon, NH More articles by this author Jan Fisher Lebanon, NH More articles by this author John Seigne Lebanon, NH More articles by this author Marc Ernstoff Lebanon, NH More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ..." @default.
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• W2013851393 title "1796 PREDICTION FOR AND MECHANISM OF RESPONSE TO DENDRITIC CELL (DC)-BASED IMMUNOTHERAPY IN METASTATIC RENAL CELL CARCINOMA (RCC)– GENE EXPRESSION PROFILING OF PERIPHERAL BLOOD LYMPHOCYTES (PBL)" @default.
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