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Enhanced antitumor effect of combination intravesical mitomycin C and bacillus Calmette-Guerin therapy in an orthotopic bladder cancer model

  • Authors:
    • Masashi Matsushima
    • Minoru Horinaga
    • Ryuichi Fukuyama
    • Hitoshi Yanaihara
    • Eiji Kikuchi
    • Makoto Kawachi
    • Masahiro Iida
    • Yoko Nakahira
    • Mototsugu Oya
    • Hirotaka Asakura
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Saitama Medical School, Saitama 350-0495, Japan, Department of Pathology, Konankosei Hospital, Aichi 483-8704, Japan, Department of Urology, Keio University School of Medicine, Tokyo 160-8582, Japan
  • Pages: 13-19
    |
    Published online on: November 23, 2010
       https://doi.org/10.3892/ol.2010.217
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Abstract

Intravesical immunotherapy with bacillus Calmette-Guerin (BCG) is currently the most successful adjuvant agent for the treatment and/or prophylaxis of non-muscle-invasive bladder cancer (NMIBC). However, NMIBCs recur in 60-70% of cases and 30% of these recurrent tumors present with a higher grade and more invasive properties. Patients that do not respond to intravesical BCG therapy are considered to be a challenge for urologists. Thus, novel conservative possibilities should be explored. To test the efficacy of a novel therapeutic approach, we examined the antitumor effect of combination therapy by intravesical administration of mitomycin C (MMC) plus BCG, infusing the two drugs simultaneously, in an orthotopic bladder cancer model. Intravesical BCG and MMC administration showed a dose-dependent survival (n=8 per group). The combination of MMC and BCG provided a significant survival advantage compared to the BCG-alone (p=0.035) and MMC-alone groups (p=0.040) (n=8 per group). The group with combined MMC/BCG exhibited a survival period similar to that achieved with an amount eight times higher that of BCG (n=10 per group). Ki-67 labeling index of cancer cells, showing tumor proliferation, was significantly lower in the combined group compared to the BCG-alone (p<0.05), MMC-alone (p<0.01) and control groups (p<0.01). No difference was detected between the combined group and the BCG-alone group with regard to CD3, T-cell infiltration and CD68 macrophage activity. The combined MMC/BCG treatment decreased the tumor appearance rate, improved the survival period and reduced the cellular proliferation rate in tumors compared to the BCG-alone treatment. The results suggest that the combined intravesical MMC/BCG treatment induced an enhanced antitumor effect against bladder tumors. The combined MMC/BCG treatment also showed a survival period similar to that achieved using a dose eight times higher of BCG-alone.
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Copy and paste a formatted citation
Spandidos Publications style
Matsushima M, Horinaga M, Fukuyama R, Yanaihara H, Kikuchi E, Kawachi M, Iida M, Nakahira Y, Oya M, Asakura H, Asakura H, et al: Enhanced antitumor effect of combination intravesical mitomycin C and bacillus Calmette-Guerin therapy in an orthotopic bladder cancer model. Oncol Lett 2: 13-19, 2011.
APA
Matsushima, M., Horinaga, M., Fukuyama, R., Yanaihara, H., Kikuchi, E., Kawachi, M. ... Asakura, H. (2011). Enhanced antitumor effect of combination intravesical mitomycin C and bacillus Calmette-Guerin therapy in an orthotopic bladder cancer model. Oncology Letters, 2, 13-19. https://doi.org/10.3892/ol.2010.217
MLA
Matsushima, M., Horinaga, M., Fukuyama, R., Yanaihara, H., Kikuchi, E., Kawachi, M., Iida, M., Nakahira, Y., Oya, M., Asakura, H."Enhanced antitumor effect of combination intravesical mitomycin C and bacillus Calmette-Guerin therapy in an orthotopic bladder cancer model". Oncology Letters 2.1 (2011): 13-19.
Chicago
Matsushima, M., Horinaga, M., Fukuyama, R., Yanaihara, H., Kikuchi, E., Kawachi, M., Iida, M., Nakahira, Y., Oya, M., Asakura, H."Enhanced antitumor effect of combination intravesical mitomycin C and bacillus Calmette-Guerin therapy in an orthotopic bladder cancer model". Oncology Letters 2, no. 1 (2011): 13-19. https://doi.org/10.3892/ol.2010.217
Copy and paste a formatted citation
x
Spandidos Publications style
Matsushima M, Horinaga M, Fukuyama R, Yanaihara H, Kikuchi E, Kawachi M, Iida M, Nakahira Y, Oya M, Asakura H, Asakura H, et al: Enhanced antitumor effect of combination intravesical mitomycin C and bacillus Calmette-Guerin therapy in an orthotopic bladder cancer model. Oncol Lett 2: 13-19, 2011.
APA
Matsushima, M., Horinaga, M., Fukuyama, R., Yanaihara, H., Kikuchi, E., Kawachi, M. ... Asakura, H. (2011). Enhanced antitumor effect of combination intravesical mitomycin C and bacillus Calmette-Guerin therapy in an orthotopic bladder cancer model. Oncology Letters, 2, 13-19. https://doi.org/10.3892/ol.2010.217
MLA
Matsushima, M., Horinaga, M., Fukuyama, R., Yanaihara, H., Kikuchi, E., Kawachi, M., Iida, M., Nakahira, Y., Oya, M., Asakura, H."Enhanced antitumor effect of combination intravesical mitomycin C and bacillus Calmette-Guerin therapy in an orthotopic bladder cancer model". Oncology Letters 2.1 (2011): 13-19.
Chicago
Matsushima, M., Horinaga, M., Fukuyama, R., Yanaihara, H., Kikuchi, E., Kawachi, M., Iida, M., Nakahira, Y., Oya, M., Asakura, H."Enhanced antitumor effect of combination intravesical mitomycin C and bacillus Calmette-Guerin therapy in an orthotopic bladder cancer model". Oncology Letters 2, no. 1 (2011): 13-19. https://doi.org/10.3892/ol.2010.217
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