Castration decreases bladder tumor growth in mice Free

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Hormone-based treatments are effective and well tolerated for treating the most common malignancies in men and women, cancers of the prostate and breast. Steroid hormones can influence mitogenic signaling pathways, apoptosis, and cell cycle checkpoints and recent studies have suggested a role in cancer of tissues not typically associated with steroid hormone control. Steroid hormones have been little studied in bladder cancer, but it has long been known that the incidence of bladder cancer in men is three fold greater than in women, a difference that cannot be attributed to environmental or lifestyle factors alone. In addition, castration reduces incidence of chemically induced bladder tumors in rodents. It is unclear if this effect is due to hormonal influences on activation of carcinogens or a direct effect on cell proliferation. We examined the effect of castration on bladder tumor growth in the UPII-SV40T transgenic mouse model of bladder cancer, which express the SV40 large T antigen specifically in the urothelium and reliably develop bladder tumors. A unique flat panel detector-based cone beam computed tomography (FPDCT) system was used to longitudinally monitor bladder tumor growth. The system acquires 290 2D projection images in 10 seconds. These images were used to produce a 3D volume with true isotropic resolution of (180 μm)³ using a filtered back projection-based Feldkamp’s (FDK) reconstruction algorithm. Using the reconstructed images, data were analyzed using Amira^® version 3.1.1-1 for MacOSX and NIH ImageJ 1.36b, and tumors were confirmed by histology. Animals were anesthetized and imaged at 24 weeks of age, randomized, and either castrated (six animals) or sham-operated (seven animals). At 28 and 32 weeks of age, animals were again anesthetized and imaged. At the 24-week imaging session, animals had bladder tumors ranging in size from 0-23 μm³. Castrated animals at 28 and 32 weeks had an average bladder tumor size of 1.5 μm³ and 2.8 μm³, respectively, while intact animals had average bladder tumor sizes of 19.1 μm³ and 37.7 μm³. These data indicate that castration can decrease bladder tumor growth in an SV40 large T antigen driven model system and that hormonal therapy of bladder cancer may be effective in controlling recurrent bladder cancer.