共查询到20条相似文献,搜索用时 15 毫秒
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Sean P. Pitroda Tong Zhou Randy F. Sweis Matthew Filippo Edwardine Labay Michael A. Beckett Helena J. Mauceri Hua Liang Thomas E. Darga Samantha Perakis Sajid A. Khan Harold G. Sutton Wei Zhang Nikolai N. Khodarev Joe G. N. Garcia Ralph R. Weichselbaum 《PloS one》2012,7(10)
Background
Vascular endothelial cells contribute to the pathogenesis of numerous human diseases by actively regulating the stromal inflammatory response; however, little is known regarding the role of endothelial inflammation in the growth of human tumors and its influence on the prognosis of human cancers.Methods
Using an experimental model of tumor necrosis factor-alpha (TNF-α)-mediated inflammation, we characterized inflammatory gene expression in immunopurified tumor-associated endothelial cells. These genes formed the basis of a multivariate molecular predictor of overall survival that was trained and validated in four types of human cancer.Results
We report that expression of experimentally derived tumor endothelial genes distinguished pathologic tissue specimens from normal controls in several human diseases associated with chronic inflammation. We trained these genes in human cancer datasets and defined a six-gene inflammatory signature that predicted significantly reduced overall survival in breast cancer, colon cancer, lung cancer, and glioma. This endothelial-derived signature predicted outcome independently of, but cooperatively with, standard clinical and pathological prognostic factors. Consistent with these findings, conditioned culture media from human endothelial cells stimulated by pro-inflammatory cytokines accelerated the growth of human colon and breast tumors in immunodeficient mice as compared with conditioned media from untreated endothelial cells.Conclusions
This study provides the first prognostic cancer gene signature derived from an experimental model of tumor-associated endothelial inflammation. These findings support the notion that activation of inflammatory pathways in non-malignant tumor-infiltrating endothelial cells contributes to tumor growth and progression in multiple human cancers. Importantly, these results identify endothelial-derived factors that could serve as potential targets for therapy in diverse human cancers. 相似文献4.
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Anna Torri Ottavio Beretta Anna Ranghetti Francesca Granucci Paola Ricciardi-Castagnoli Maria Foti 《PloS one》2010,5(2)
Dendritic cells (DCs) constitute a heterogeneous group of antigen-presenting leukocytes important in activation of both innate and adaptive immunity. We studied the gene expression patterns of DCs incubated with reagents inducing their activation or inhibition. Total RNA was isolated from DCs and gene expression profiling was performed with oligonucleotide microarrays. Using a supervised learning algorithm based on Random Forest, we generated a molecular signature of inflammation from a training set of 77 samples. We then validated this molecular signature in a testing set of 38 samples. Supervised analysis identified a set of 44 genes that distinguished very accurately between inflammatory and non inflammatory samples. The diagnostic performance of the signature genes was assessed against an independent set of samples, by qRT-PCR. Our findings suggest that the gene expression signature of DCs can provide a molecular classification for use in the selection of anti-inflammatory or adjuvant molecules with specific effects on DC activity. 相似文献
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Uncovering a macrophage transcriptional program by integrating evidence from motif scanning and expression dynamics
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Ramsey SA Klemm SL Zak DE Kennedy KA Thorsson V Li B Gilchrist M Gold ES Johnson CD Litvak V Navarro G Roach JC Rosenberger CM Rust AG Yudkovsky N Aderem A Shmulevich I 《PLoS computational biology》2008,4(3):e1000021
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