1. Prognostic significance of IL-8-STAT-3 pathway in astrocytomas: Correlation with IL-6, VEGF and microvessel morphometry
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Piperi, Christina, Samaras, Vassilis, Levidou, Georgia, Kavantzas, Nikolaos, Boviatsis, Efstathios, Petraki, Kalliopi, Grivas, Athanasios, Barbatis, Calypso, Varsos, Vassilis, Patsouris, Efstratios, and Korkolopoulou, Penelope
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ASTROCYTOMAS , *CANCER prognosis , *CANCER immunology , *INTERLEUKINS , *IMMUNOSUPPRESSIVE agents , *CANCER cell growth , *GENE expression , *VASCULAR endothelial growth factors - Abstract
Abstract: Malignant astrocytomas are highly vascular neoplasms characterized by a potent angiogenic and immunosuppressive phenotype. Th2-cytokines (IL-6/IL-8) are implicated as major regulators of glioma cell growth and invasiveness. STAT-3, a downstream transducer of cytokine signaling is positively associated with tumor angiogenesis. The present study aimed to investigate the expression of IL-8 and p-STAT-3 in 97 diffusely infiltrating astrocytomas of various grades, in relation to IL-6, VEGF, clinicopathological features, microvascular characteristics and patients’ survival. IL-8 expression was localized in neoplastic cells, being associated with p-STAT-3 (p =0.0013), IL-6 (p =0.0004) and VEGF (p <0.0001) around areas of necrosis as well as in perivascular inflammatory and endothelial cells. All the molecules under study correlated with tumor grade and degree of necrosis (p <0.05, respectively). p-STAT-3, IL-8 and VEGF expression was positively associated with microvessel density (p =0.0491, p <0.0001 and p =0.0118, respectively). Univariate analysis indicated that overexpression of IL-8 and IL-6 adversely affected survival in the entire cohort whereas increased p-STAT-3 expression was predictive of improved survival in high grade (III/IV) astrocytomas (p =0.0032). In multivariate analysis only IL-8 expression (p =0.043) retained its significance. The prognostic significance of IL-8 expression and its correlation with p-STAT-3 and VEGF implicates this novel signaling pathway in astroglial tumors progression providing new targets for effective immunotherapy. [Copyright &y& Elsevier]
- Published
- 2011
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