title: Talc mediates angiostasis in malignant pleural effusions via endostatin induction.
abstract: Talc remains the most effective sclerosing agent for pleurodesis. However, its mechanism of action in resolving pleural malignant disease remains unclear. The present study evaluated the angiogenic balance in the pleural space in patients with malignant pleural effusions (MPE) following talc insufflation. Patient pleural fluid samples were collected both before and after talc insufflation. The ability of pleural mesothelial cells (PMC) and malignant mesothelioma cells (MMC) to produce endostatin in vitro was compared. The biological effects of pleural fluids and conditioned media from talc-activated PMC on endothelial cells were evaluated by performing proliferation, invasion, tube formation and apoptosis assays. Pleural fluids from patients with MPE who received thoracoscopic talc insufflation contained significantly higher levels of endostatin (median 16.75 ng.mL(-1)) compared with pre-talc instillation (1.06 ng.mL(-1)). Talc-activated PMC released significantly greater amounts of endostatin (mean+/-SEM 1052.39+/-38.66 pg.mL(-1)) when compared with a MMC line (134.73+/-8.72 pg.mL(-1)). In conclusion, talc alters the angiogenic balance in the pleural space from a biologically active and angiogenic environment to an angiostatic milieu. Functional improvement following talc poudrage in patients with malignant pleural effusions may, in part, reflect these alterations in the pleural space.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Dept of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: N
authors.initials: N
authors.lastname: Nasreen
authors.forename: N
authors.initials: N
authors.lastname: Najmunnisa
authors.forename: K A
authors.initials: KA
authors.lastname: Mohammed
authors.forename: S
authors.initials: S
authors.lastname: Brown
authors.forename: Y
authors.initials: Y
authors.lastname: Su
authors.forename: P S
authors.initials: PS
authors.lastname: Sriram
authors.forename: B
authors.initials: B
authors.lastname: Moudgil
authors.forename: R
authors.initials: R
authors.lastname: Loddenkemper
authors.forename: V B
authors.initials: VB
authors.lastname: Antony
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D043169:Endostatins / Q000378:metabolism*; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010316:Particle Size; D016066:Pleural Effusion, Malignant / Q000628:therapy; D018700:Pleurodesis / Q000009:adverse effects* / Q000379:methods; D013627:Talc / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D043169:Endostatins; D013627:Talc