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Targeting vascular endothelial growth factor blockade: ascites and pleural effusion formation
H M Verheul1, K Hoekman, A S Jorna
1Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
The Oncologist
|May 10, 2000
Summary
Malignant ascites and pleural effusions (PE) contain high levels of biologically active vascular endothelial growth factor (VEGF). Blocking VEGF activity, such as with SU5416, may benefit cancer patients experiencing recurrent fluid accumulation.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Ascites and pleural effusion (PE) are common in advanced cancer, causing significant patient distress.
- Vascular Endothelial Growth Factor (VEGF) is implicated in malignant fluid accumulation based on preclinical models.
Purpose of the Study:
- To investigate the role of VEGF in the biological activity of ascites and PE in cancer patients.
- To determine if blocking VEGF activity can reduce the effects of ascites and PE on endothelial cells.
Main Methods:
- Measured VEGF activity in ascites and PE from 58 cancer patients.
- Utilized an endothelial cell proliferation assay with human umbilical vein endothelial cells to assess biological activity.
- Tested the effect of a VEGF-neutralizing antibody and a VEGF receptor inhibitor (SU5416).
Main Results:
- Significantly higher VEGF concentrations were found in malignant ascites/PE compared to nonmalignant effusions.
- Biologically active samples showed higher VEGF levels and stimulated endothelial cell proliferation.
- VEGF blockade with an antibody or SU5416 significantly inhibited endothelial cell proliferation.
Conclusions:
- Malignant ascites and PE are rich in biologically active VEGF.
- VEGF blockade presents a promising therapeutic strategy for managing recurrent ascites and PE in cancer patients.
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