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BCG-INDUCED URINARY CYTOKINES INHIBIT MICROVASCULAR ENDOTHELIAL CELL PROLIFERATION

2000; Lippincott Williams & Wilkins; Volume: 163; Issue: 6 Linguagem: Inglês

10.1016/s0022-5347(05)67620-3

1527-3792

Christian P. Pavlovich, Birgit M. Kräling, Robert Stewart, Xiaohong Chen, Bernard H. Bochner, Andrew D. Luster, Dix P. Poppas, Michael A. O’Donnell,

Angiogenesis and VEGF in Cancer

No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Jun 2000BCG-INDUCED URINARY CYTOKINES INHIBIT MICROVASCULAR ENDOTHELIAL CELL PROLIFERATION CHRISTIAN P. PAVLOVICH, BIRGIT M. KRÄLING, ROBERT J. STEWART, XIAOHONG CHEN, BERNARD H. BOCHNER, ANDREW D. LUSTER, DIX P. POPPAS, and MICHAEL A. O’DONNELL CHRISTIAN P. PAVLOVICHCHRISTIAN P. PAVLOVICH More articles by this author , BIRGIT M. KRÄLINGBIRGIT M. KRÄLING More articles by this author , ROBERT J. STEWARTROBERT J. STEWART More articles by this author , XIAOHONG CHENXIAOHONG CHEN More articles by this author , BERNARD H. BOCHNERBERNARD H. BOCHNER More articles by this author , ANDREW D. LUSTERANDREW D. LUSTER More articles by this author , DIX P. POPPASDIX P. POPPAS More articles by this author , and MICHAEL A. O’DONNELLMICHAEL A. O’DONNELL More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)67620-3AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail 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. References 1 : Intravesical chemotherapy versus immunotherapy for superficial bladder cancer. Semin Urol Oncol1996; 14: 17. Google Scholar 2 : Long-term complete remission in bladder carcinoma in situ with intravesical TICE bacillus Calmette-Guerin: Overview analysis of six phase II clinical trials. Urology1991; 38: 507. Google Scholar 3 : Superficial bladder cancer: decreasing the risk of recurrence. Oncology1996; 10: 1617. Google Scholar 4 : Analysis of mucosal bladder leucocyte subpopulations in patients treated with intravesical Bacillus Calmette-Guerin. Urol Res1989; 17: 299. 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Google Scholar From the James Buchanan Brady Foundation, Department of Urology, The New York Hospital - Cornell Medical Center, New York, New York, the Surgical Research Laboratory, Department of Surgery, Children’s Hospital - Harvard Medical School, Boston, Massachusetts, the Division of Urology, Department of Surgery, The Toronto Hospital, University of Toronto, Toronto, Canada, the Division of Urology, Department of Surgery, Beth Israel Deaconess Medical Center - Harvard Medical School, Boston, Massachusetts, the Department of Urology, USC/Norris Comprehensive Cancer Center, Los Angeles, California, and the Infectious Disease Unit, Department of Medicine, Massachusetts General Hospital - Harvard Medical School, Charlestown, Massachusetts© 2000 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byReis L, Ferreira U, Billis A, Cagnon V and Fávaro W (2018) Anti-Angiogenic Effects of the Superantigen Staphylococcal Enterotoxin B and Bacillus Calmette-Guérin Immunotherapy for Nonmuscle Invasive Bladder CancerJournal of Urology, VOL. 187, NO. 2, (438-445), Online publication date: 1-Feb-2012.O’DONNELL M, KROHN J and DeWOLF W (2018) SALVAGE INTRAVESICAL THERAPY WITH INTERFERON-α2B PLUS LOW DOSE BACILLUS CALMETTE-GUERIN IS EFFECTIVE IN PATIENTS WITH SUPERFICIAL BLADDER CANCER IN WHOM BACILLUS CALMETTE-GUERIN ALONE PREVIOUSLY FAILEDJournal of Urology, VOL. 166, NO. 4, (1300-1305), Online publication date: 1-Oct-2001. Volume 163Issue 6June 2000Page: 2014-2021 Advertisement Copyright & Permissions© 2000 by American Urological Association, Inc.Keywordsendothelial cellsangiogenesisurinary cytokinesIP-10TNF-αBCGMetricsAuthor Information CHRISTIAN P. PAVLOVICH More articles by this author BIRGIT M. KRÄLING More articles by this author ROBERT J. STEWART More articles by this author XIAOHONG CHEN More articles by this author BERNARD H. BOCHNER More articles by this author ANDREW D. LUSTER More articles by this author DIX P. POPPAS More articles by this author MICHAEL A. O’DONNELL More articles by this author Expand All Advertisement PDF downloadLoading ...