Clinical Significance of Heme Oxygenase-1 Expression in Non-Muscle-Invasive Bladder Cancer

Introduction: In several malignant diseases, elevated heme oxygenase-1 (HO-1) is associated with progression or resistance to chemotherapy. We evaluated the clinical significance of HO-1 expression in non-muscle-invasive bladder cancer. Patients and Methods: We examined 109 patients with non-muscle-...

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Veröffentlicht in:Urologia internationalis 2010-01, Vol.85 (3), p.355-363
Hauptverfasser: Miyake, Makito, Fujimoto, Kiyohide, Anai, Satoshi, Ohnishi, Sayuri, Nakai, Yasushi, Inoue, Takeshi, Matsumura, Yoshiaki, Tomioka, Atsushi, Ikeda, Tomohiro, Tanaka, Nobumichi, Hirao, Yoshihiko
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Sprache:eng
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Zusammenfassung:Introduction: In several malignant diseases, elevated heme oxygenase-1 (HO-1) is associated with progression or resistance to chemotherapy. We evaluated the clinical significance of HO-1 expression in non-muscle-invasive bladder cancer. Patients and Methods: We examined 109 patients with non-muscle-invasive bladder cancer. The immunoexpression of HO-1, p53, and Ki-67 was analyzed using paraffin-embedded tissue from transurethral resection in comparison with the clinicopathological variables. Results: Positive expression of HO-1 was found in 66 of 109 tumors (61%), and the positivity of HO-1 correlated significantly with high tumor grade and the altered expression patterns of p53 and Ki-67. In our analysis of 16 cases treated by intravesical administration of anthracyclines, the positive expression of HO-1 correlated with poor disease-free survival (p = 0.015). In in vitro experiments using urothelial cancer cell lines, HO-1 upregulation was observed by exposure to doxorubicin. Moreover, siRNA-mediated suppression of HO-1 upregulation sensitized the urothelial cancer cells to doxorubicin. Conclusions: Our findings suggested that resistance against anthracyclines correlated with HO-1 and expression analysis of HO-1 may be a useful predictive marker for intravesical administration of anthracyclines.
ISSN:0042-1138
1423-0399
DOI:10.1159/000317785