Zaixian Zhang1, Qingquan Xu2, Xiaobo Huang2, Jia Yang1, Yanhong Xu1, Guixiang Zhang1. 1. Department of Radiology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200080, China. 2. Department of Urology, Peking University People's Hospital Beijing 100044, China.
Abstract
OBJECTIVE: To compare the efficacy of early versus delayed surgical castration on prolonging survival and further to investigate the anticancer effect and potential value of targeting androgen in the therapeutic intervention of bladder cancer. MATERIALS AND METHODS: N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) was used to induce bladder cancer in male mice. Mice were randomly divided into three groups: the early castration group (on which castration was perform at 4 weeks after first time of BBN administration), the delayed castration group (on which castration was perform at 20 weeks after first time of BBN administration), and the sham-castrated group. Mice were monitored daily throughout their lifespan until cancer-related death or the progress of an obviously moribund appearance, at which time the mice were killed. Androgen receptor expression and cell proliferation and apoptosis analysis were also evaluated. RESULTS: The average lifespan in early castration, delayed castration and sham-castrated groups were 315.8 days, 300.1 days and 254.6 days, respectively. Early castration conferred a statistically significant survival advantage when compared with the sham-castrated group (P < 0.05). However, the difference in the lifespan between the delayed castration group and the sham-castrated group was not statistically significant (P = 0.198). Both early and delayed castration significantly increased apoptosis of tumor cells when compared with the sham-castrated group (both P < 0.01), which was also accompanied by a significant decrease in cells proliferation (both P < 0.01). Prolonged survival of mice in early castration group was correlated with a lower G/B value (genitourinary tract weight/body weight) at death than the sham-castrated mice. CONCLUSION: Early castration had an overall survival benefit when compared with the sham-castrated treatment in BBN-induced bladder cancer mice. This finding may enhance the feasibility of androgen ablation treatment in patients with bladder cancer.
OBJECTIVE: To compare the efficacy of early versus delayed surgical castration on prolonging survival and further to investigate the anticancer effect and potential value of targeting androgen in the therapeutic intervention of bladder cancer. MATERIALS AND METHODS:N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) was used to induce bladder cancer in male mice. Mice were randomly divided into three groups: the early castration group (on which castration was perform at 4 weeks after first time of BBN administration), the delayed castration group (on which castration was perform at 20 weeks after first time of BBN administration), and the sham-castrated group. Mice were monitored daily throughout their lifespan until cancer-related death or the progress of an obviously moribund appearance, at which time the mice were killed. Androgen receptor expression and cell proliferation and apoptosis analysis were also evaluated. RESULTS: The average lifespan in early castration, delayed castration and sham-castrated groups were 315.8 days, 300.1 days and 254.6 days, respectively. Early castration conferred a statistically significant survival advantage when compared with the sham-castrated group (P < 0.05). However, the difference in the lifespan between the delayed castration group and the sham-castrated group was not statistically significant (P = 0.198). Both early and delayed castration significantly increased apoptosis of tumor cells when compared with the sham-castrated group (both P < 0.01), which was also accompanied by a significant decrease in cells proliferation (both P < 0.01). Prolonged survival of mice in early castration group was correlated with a lower G/B value (genitourinary tract weight/body weight) at death than the sham-castrated mice. CONCLUSION: Early castration had an overall survival benefit when compared with the sham-castrated treatment in BBN-induced bladder cancermice. This finding may enhance the feasibility of androgen ablation treatment in patients with bladder cancer.
Entities:
Keywords:
Androgen receptor; bladder cancer; castration; mouse model
Authors: C J Grubbs; R A Lubet; A T Koki; K M Leahy; J L Masferrer; V E Steele; G J Kelloff; D L Hill; K Seibert Journal: Cancer Res Date: 2000-10-15 Impact factor: 12.701