Kerem Teke1, Hasan Yilmaz2, Ali Kemal Uslubas2, Gurler Akpinar3, Murat Kasap3, Oguz Mutlu4, Demir Kursat Yildiz5, Nil Guzel3, Ozdal Dillioglugil2. 1. Department of Urology, Kocaeli University School of Medicine, 41380, Kocaeli, Turkey. drtekekerem@gmail.com. 2. Department of Urology, Kocaeli University School of Medicine, 41380, Kocaeli, Turkey. 3. Department of Medical Biology, Kocaeli University School of Medicine, Kocaeli, Turkey. 4. Department of Pharmacology, Kocaeli University School of Medicine, Kocaeli, Turkey. 5. Department of Pathology, Kocaeli University School of Medicine, Kocaeli, Turkey.
Abstract
PURPOSE: Recent studies have shown that Aurora-A expression is associated with bladder cancer initiation and progression. In this study, the effects of intravesical Aurora-A inhibitor Alisertib (ALS) and bacillus Calmette-Guérin (BCG) were compared on bladder carcinogenesis. METHODS: Two mg N-Methyl-N-nitrosourea was administered intravesically to forty of Wistar-albino rats every other week for 8 weeks. At week 10, rats were divided into four groups (10/group): No-treatment (vehicle), ALS-alone, BCG-alone, and ALS + BCG. The intravesical treatment of ALS, BCG, and ALS plus BCG was performed once a week for 6 weeks. At week 16, bladders were collected for immunohistopathological and Western blot analysis. The cell cycle regulators p53, p21, Aurora-A, phosphorylated Aurora-A (p-Aurora-A), and apoptotic marker cleavage of poly [ADP-ribose] polymerase (c-PARP) were determined by Western blot. RESULTS: Histopathologically relatively healthy urothelium was observed in ALS + BCG group (87.5%) compared to the ALS-alone (50%) and the BCG-alone (50%) groups. The lowest expression of p21 and p53 was detected in the BCG-alone, while the highest level of expression was evident in no-treatment group. The ALS treatment alone caused a slight decrease in Aurora-A while there was a dramatic decrease in p-Aurora-A in comparison to no-treatment group. In overall combined treatment with ALS + BCG significantly increased c-PARP compared to all mono-treatments, and decreased all cell cycle parameters compared to no-treatment group. CONCLUSIONS: Although intravesical ALS treatment has similar antiproliferative effects like BCG, ALS + BCG combined treatment led to a best histopathologic and apoptotic response. Consequently, BCG combined with Aurora-A inhibition may provide a new intravesical treatment modality in the prevention of bladder carcinogenesis.
PURPOSE: Recent studies have shown that Aurora-A expression is associated with bladder cancer initiation and progression. In this study, the effects of intravesical Aurora-A inhibitor Alisertib (ALS) and bacillus Calmette-Guérin (BCG) were compared on bladder carcinogenesis. METHODS: Two mg N-Methyl-N-nitrosourea was administered intravesically to forty of Wistar-albino rats every other week for 8 weeks. At week 10, rats were divided into four groups (10/group): No-treatment (vehicle), ALS-alone, BCG-alone, and ALS + BCG. The intravesical treatment of ALS, BCG, and ALS plus BCG was performed once a week for 6 weeks. At week 16, bladders were collected for immunohistopathological and Western blot analysis. The cell cycle regulators p53, p21, Aurora-A, phosphorylated Aurora-A (p-Aurora-A), and apoptotic marker cleavage of poly [ADP-ribose] polymerase (c-PARP) were determined by Western blot. RESULTS: Histopathologically relatively healthy urothelium was observed in ALS + BCG group (87.5%) compared to the ALS-alone (50%) and the BCG-alone (50%) groups. The lowest expression of p21 and p53 was detected in the BCG-alone, while the highest level of expression was evident in no-treatment group. The ALS treatment alone caused a slight decrease in Aurora-A while there was a dramatic decrease in p-Aurora-A in comparison to no-treatment group. In overall combined treatment with ALS + BCG significantly increased c-PARP compared to all mono-treatments, and decreased all cell cycle parameters compared to no-treatment group. CONCLUSIONS: Although intravesical ALS treatment has similar antiproliferative effects like BCG, ALS + BCG combined treatment led to a best histopathologic and apoptotic response. Consequently, BCG combined with Aurora-A inhibition may provide a new intravesical treatment modality in the prevention of bladder carcinogenesis.
Authors: Maximilian Burger; James W F Catto; Guido Dalbagni; H Barton Grossman; Harry Herr; Pierre Karakiewicz; Wassim Kassouf; Lambertus A Kiemeney; Carlo La Vecchia; Shahrokh Shariat; Yair Lotan Journal: Eur Urol Date: 2012-07-25 Impact factor: 20.096
Authors: S E Coupland; N Bechrakis; A Schüler; I Anagnostopoulos; M Hummel; N Bornfeld; H Stein Journal: Br J Ophthalmol Date: 1998-08 Impact factor: 4.638
Authors: Kerem Teke; Tayyar A Ozkan; Oguz O Cebeci; Hasan Yilmaz; Muhammed E Keles; Levend Ozkan; Meltem O Dillioglugil; Demir K Yildiz; Ozdal Dillioglugil Journal: Exp Anim Date: 2017-02-22