title: The angiogenetic pathway in malignant pleural effusions: Pathogenetic and therapeutic implications.
abstract: Increased permeability of the pleural microvasculature is generally attributed to the substances that are released in inflammatory and malignant pleural effusions, although the exact pathogenetic mechanisms of malignant pleural effusions are unclear. Current therapies used to prevent the re-accumulation of pleural fluid and relieve symptoms are of variable efficacy and may cause serious adverse effects. Understanding the mechanisms of fluid accumulation would hopefully permit the development of more specific, effective and safer treatment modalities. Angiogenesis, pleural vascular increased permeability and inflammation are considered central to the pathogenesis of malignant pleural effusions. Vascular endothelial growth factor (VEGF) is a member of the VEGF/platelet-derived factor gene family and consists of at least six isoforms. Since it was shown that VEGF contributes to the formation of malignant pleural effusions, there have been some attempts to implicate, therapeutically, this finding using different molecules (ZD6474, PTK 787 and bevacizumab). However, the role of the biological axis of VEGF and angiopoietins needs further investigation in both the pathogenesis and the treatment of malignant pleural effusion. In both non-small-cell lung carcinoma and breast cancer, it has been shown that the ligand for CXCR4, CXCL12 or SDF-1α, exhibited peak levels of expression in organs that were the preferred destination for their respective metastases. Recent findings imply that new therapeutic strategies aimed at blocking the SDF-1-CXCR4 axis may have significant applications for patients by modulating the trafficking of hemato/lymphopoietic cells and inhibiting the metastatic behavior of tumor cells as well. The purpose of this report is to review novel pathogenetic and therapeutic implications regarding the angiogenetic pathways in malignant pleural effusions.
authors.affiliation: Department of Thoracic Medicine, Medical School, University of Crete, Heraklion,  Greece.
authors.forename: Foteini
authors.initials: F
authors.lastname: Economidou
authors.forename: George
authors.initials: G
authors.lastname: Margaritopoulos
authors.forename: Katerina M
authors.initials: KM
authors.lastname: Antoniou
authors.forename: Nikolaos M
authors.initials: NM
authors.lastname: Siafakas