Abstract | PURPOSE: EXPERIMENTAL DESIGN: MPE was induced by intrapleural injection of murine adenocarcinoma cells in C57BL/6 mice. Animals were given twice-weekly intraperitoneal injections of 40 mg/kg MuTekdeltaFc or vehicle. MuTekdeltaFc is a soluble Tie2 (sTie2) receptor that binds murine angiopoietins thereby disrupting their interaction with Tie2 receptors expressed on tissues. Animals were killed on day 14. RESULTS:
Angiopoietin/Tie2 axis blockade significantly reduced pleural fluid volume and pleural tumor foci. The mean +/- SEM pleural fluid volumes were 617 +/- 48 microl and 316 +/- 62 microl for the control and treated groups, respectively (P = .001), whereas the mean +/- SEM tumor foci were 7.3 +/- 1.0 and 3.0 +/- 0.52 for the control and treated groups, respectively (P = .001). In addition, tumor-associated cachexia, tumor angiogenesis, pleural vascular permeability, recruitment of inflammatory cells to the pleural cavity, and local elaboration of vascular endothelial growth factor and interleukin 6 were also downregulated, and tumor cell apoptosis was induced in animals treated with the inhibitor. CONCLUSIONS: Our results indicate that the angiopoietin/Tie2 axis is an important component of MPE pathogenesis. Further studies are required to determine whether therapeutic interventions targeting this pathway could be beneficial for patients with MPE.
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Authors | Charalampos Moschos, Ioannis Psallidas, Androniki Kollintza, Sophia Karabela, Andreas Papapetropoulos, Spyros Papiris, Richard W Light, Charis Roussos, Georgios T Stathopoulos, Ioannis Kalomenidis |
Journal | Neoplasia (New York, N.Y.)
(Neoplasia)
Vol. 11
Issue 3
Pg. 298-304
(Mar 2009)
ISSN: 1476-5586 [Electronic] United States |
PMID | 19242611
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiopoietins
- Receptor, TIE-2
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Topics |
- Adenocarcinoma
(complications)
- Angiopoietins
(metabolism)
- Animals
- Apoptosis
(physiology)
- Capillary Permeability
(physiology)
- In Situ Nick-End Labeling
- Inflammation
(metabolism)
- Mice
- Mice, Inbred C57BL
- Pleura
(pathology)
- Pleural Effusion, Malignant
(etiology, metabolism)
- Receptor, TIE-2
(metabolism)
- Signal Transduction
(physiology)
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