Chemoprevention of BBN-Induced Bladder Carcinogenesis by the Selective Estrogen Receptor Modulator Tamoxifen

Bladder cancer is the fifth most frequent tumor in men and ninth in women in the United States. Due to a high likelihood of recurrence, effective chemoprevention is a significant unmet need. Estrogen receptors (ERs), primarily ERβ, are expressed in normal urothelium and urothelial carcinoma, and blocking ER function with selective ER modulators such as tamoxifen inhibits bladder cancer cell proliferation in vitro. Herein, the chemoprotective potential of tamoxifen was evaluated in female mice exposed to the bladder-specific carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Carcinogen treatment resulted in a 76% tumor incidence and increased mean bladder weights in comparison to controls. In contrast, mice receiving tamoxifen concurrent (8–20 weeks) or concurrent and subsequent (8–32 weeks) to BBN administration had no change in bladder weight and only 10% to 14% incidence of tumors. Non-muscle-invasive disease was present in animals treated with tamoxifen before (5–8 weeks) or after (20–32 weeks) BBN exposure, while incidence of muscle-invasive bladder carcinoma was reduced. ERβ was present in all mice and thus is a potential mediator of the tamoxifen chemoprotective effect. Surprisingly, ERα expression, which was detected in 74% of the mice exposed to BBN alone but not in any controlmice, was correlated with tumor incidence, indicating a possible role for this receptor in carcinogen-induced urothelial tumorigenesis. Thus, these data argue that both ERα and ERβ play a role in modulating carcinogen-induced bladder tumorigenesis. Administration of tamoxifen should be tested as a chemopreventive strategy for patients at high risk for bladder cancer recurrence.     

Reproductive biology of the endemic cyprinid fish Hypselobarbus thomassi (Day, 1874) from Kallada River in the Western Ghats,India

The study provides new information on the reproductive biology of Hypselobarbus thomassi (Day, 1874) an endemic cyprinid fish in the Western Ghats–a biodiversity hotspot of India. A total of 384 specimens (males = 244 and females = 140) were collected monthly from April 2009 to March 2011 from Kallada River of Southern part of Western Ghats, India. Monthly sex ratio indicated that males predominated in the fishery, and an overall sex ratio was significantly different from the expected value of 1:1 (male:female = 1:0.57, x² = 28.17, p < .01). Based on the monthly analysis of gonadosomatic index (GSI) and the proportion of mature individuals, the spawning season of H. thomassi occurred between May to October with a peak in June to August. The length at first maturity (L₅₀) recorded was 290 mm TL in males and 330 mm TL in females. The absolute fecundity ranged between 305 (234 mm TL) to 1,089 (414 mm TL) and relative fecundity oscillated between 77.3–220.69 oocytes/g of fish. The fecundity established a linear relationship with total length, body weight and ovary weight. The findings of this study would be very effective to impose sustainable conservation plan for this threatened species in Kallada River and other Western Ghats river systems.