@article{3004193,
    title = "Prognostic significance of IL-8-STAT-3 pathway in astrocytomas: Correlation with IL-6, VEGF and microvessel morphometry",
    author = "Piperi, C. and Samaras, V. and Levidou, G. and Kavantzas, N. and Boviatsis, E. and Petraki, K. and Grivas, A. and Barbatis, C. and Varsos, V. and Patsouris, E. and Korkolopoulou, P.",
    journal = "Cytokine",
    year = "2011",
    volume = "55",
    number = "3",
    pages = "387-395",
    issn = "1043-4666, 1096-0023",
    doi = "10.1016/j.cyto.2011.05.012",
    keywords = "interleukin 6;  interleukin 8;  STAT3 protein;  vasculotropin, adult;  aged;  article;  astrocytoma;  cancer grading;  cancer growth;  cancer survival;  cell infiltration;  clinical feature;  controlled study;  disease association;  disease severity;  female;  gene overexpression;  human;  human tissue;  immunohistochemistry;  immunoreactivity;  major clinical study;  male;  microvasculature;  predictive value;  priority journal;  prognosis;  protein expression;  protein function;  protein localization;  protein targeting;  signal transduction, Adult;  Aged;  Aged, 80 and over;  Astrocytoma;  Brain Neoplasms;  Cohort Studies;  Female;  Humans;  Immunotherapy;  Interleukin-6;  Interleukin-8;  Male;  Microvessels;  Middle Aged;  Neovascularization, Pathologic;  Prognosis;  Signal Transduction;  STAT3 Transcription Factor;  Tumor Markers, Biological;  Vascular Endothelial Growth Factor A;  Vascular Neoplasms",
    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. © 2011 Elsevier Ltd."
}