Journal article
BCG-INDUCED URINARY CYTOKINES INHIBIT MICROVASCULAR ENDOTHELIAL CELL PROLIFERATION
The Journal of urology, Vol.163(6), pp.2014-2021
06/2000
DOI: 10.1016/S0022-5347(05)67620-3
PMID: 10799249
Abstract
Purpose: Angiogenesis is thought to depend on a net balance of molecules that inhibit or stimulate microvascular endothelial cells. A variety of molecules that affect angiogenesis are induced locally by the administration of intravesical bacille Calmette-Guerin (BCG) for superficial bladder cancer. We sought to determine whether BCG-induced urinary cytokines alter the effects of patient urine on assays of angiogenic activity. Materials and Methods: Patients undergoing BCG treatment provided urine samples before and at peak cytokine production times after BCG instillation. Fifty-four urine samples from 8 patients were analyzed by ELISA for a panel of molecules known to affect angiogenesis, and tested for angiogenic activity in human dermal microvascular endothelial cell (HDMEC) proliferation and migration assays. To assess the role of specific BCG-induced cytokines, urinary HDMEC proliferation assays were repeated in the presence of neutralizing antibodies to tumor necrosis factor-alpha (TNF-α), interferon-inducible protein-10 (IP- 10), and/or interferon-gamma (IFN-γ). Results: Urinary IFN-γ, IP-10, TNF- α, and vascular endothelial growth factor (VEGF) were induced to nanogram/ml amounts by BCG treatment. While pre-BCG treatment urine samples minimally stimulated microvascular endothelial cell proliferation (+ 9%), post-BCG treatment urine became progressively inhibitory to endothelial cells (to - 85%, p = 0.005) during weekly treatment courses. Neutralizing antibodies to TNF-α or to IP-10, either alone or in combination, greatly reduced this inhibitory effect. Conclusions: Intravesical BCG induces a cytokine-rich urinary microenvironment that is inhibitory to human endothelial cells. Urinary cytokine profiles and assays of angiogenic inhibition may provide prognostically important information regarding BCG treatment outcomes.
Details
- Title: Subtitle
- BCG-INDUCED URINARY CYTOKINES INHIBIT MICROVASCULAR ENDOTHELIAL CELL PROLIFERATION
- Creators
- CHRISTIAN P. Pavlovich - NewYork–Presbyterian HospitalBIRGIT M. Kräling - NewYork–Presbyterian HospitalROBERT J. Stewart - NewYork–Presbyterian HospitalXIAOHONG Chen - NewYork–Presbyterian HospitalBERNARD H. Bochner - NewYork–Presbyterian HospitalANDREW D. Luster - NewYork–Presbyterian HospitalDIX P. Poppas - NewYork–Presbyterian HospitalMICHAEL A. O’DONNELL - NewYork–Presbyterian Hospital
- Resource Type
- Journal article
- Publication Details
- The Journal of urology, Vol.163(6), pp.2014-2021
- DOI
- 10.1016/S0022-5347(05)67620-3
- PMID
- 10799249
- ISSN
- 0022-5347
- eISSN
- 1527-3792
- Language
- English
- Date published
- 06/2000
- Academic Unit
- Urology
- Record Identifier
- 9984320070802771
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