TGF-β regulation of gene expression at early and late stages of HPV16-mediated transformation of human keratinocytes

AbstractIn our in vitro model for HPV16-mediated transformation, HPV16-immortalized human keratinocytes (HKc/HPV16) give rise to differentiation resistant, premalignant cells (HKc/DR). HKc/DR, but not HKc/HPV16, are resistant to growth inhibition by transforming growth factor beta (TGF-β), due to a partial loss of TGF-β receptor type I. We show that TGF-β activates a Smad-responsive reporter construct in HKc/DR to about 50% of the maximum levels of activation observed in HKc/HPV16. To investigate the functional significance of residual TGF-β signaling in HKc/DR, we compared gene expression profiles elicited by TGF-β treatment of HKc/HPV16 and HKc/DR on Agilent 44k human whole genome microarrays. TGF-β altered the expression of cell cycle and MAP kinase pathway genes in HKc/HPV16, but not in HKc/DR. However, epithelial–mesenchymal transition (EMT) responses to TGF-β were comparable in HKc/HPV16 and HKc/DR, indicating that the signaling pathways through which TGF-β elicits growth inhibition diverge from those that induce EMT in HPV16-transformed cells

MOESM4 of Baseline immune profile by CyTOF can predict response to an investigational adjuvanted vaccine in elderly adults

Additional file 4. Workflow to perform viSNE analysis on antigen-specific cells

MOESM1 of Baseline immune profile by CyTOF can predict response to an investigational adjuvanted vaccine in elderly adults

Additional file 1. Mock subtracted IFNÎł responses at Day 1, at Day 8 undepleted, CD4 depleted and CD8 depleted

MOESM2 of Baseline immune profile by CyTOF can predict response to an investigational adjuvanted vaccine in elderly adults

Additional file 2. CyTOF workflow

MOESM3 of Baseline immune profile by CyTOF can predict response to an investigational adjuvanted vaccine in elderly adults

Additional file 3. Percentage of RSV specific CD3+CD4+ and CD3+CD8+ responses

Human papillomavirus status and gene expression profiles of oropharyngeal and oral cancers from European American and African American patients

10.1002/hed.24072HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK38S1E694-E70

A Gene Expression Classifier of Node-Positive Colorectal Cancer1,2

We used digital long serial analysis of gene expression to discover gene expression differences between node-negative and node-positive colorectal tumors and developed a multigene classifier able to discriminate between these two tumor types. We prepared and sequenced long serial analysis of gene expression libraries from one node-negative and one node-positive colorectal tumor, sequenced to a depth of 26,060 unique tags, and identified 262 tags significantly differentially expressed between these two tumors (P < 2 x 10-6). We confirmed the tag-to-gene assignments and differential expression of 31 genes by quantitative real-time polymerase chain reaction, 12 of which were elevated in the node-positive tumor. We analyzed the expression levels of these 12 upregulated genes in a validation panel of 23 additional tumors and developed an optimized seven-gene logistic regression classifier. The classifier discriminated between node-negative and node-positive tumors with 86% sensitivity and 80% specificity. Receiver operating characteristic analysis of the classifier revealed an area under the curve of 0.86. Experimental manipulation of the function of one classification gene, Fibronectin, caused profound effects on invasion and migration of colorectal cancer cells in vitro. These results suggest that the development of node-positive colorectal cancer occurs in part through elevated epithelial FN1 expression and suggest novel strategies for the diagnosis and treatment of advanced disease