Katsuhiro Babaya

Effects of single chemotherapeutic agents on development of urinary bladder tumor induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in rats

SummaryChemotherapeutic agents were evaluated for effect on the development of urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in male Wistar strain rats. Seven hundred and two rats were given 0.05% BBN in drinking water for 8 weeks. After BBN treatment, the animals were divided into 26 groups to follow regimens of single chemotherapy. All drugs were administered intraperitoneally except in one group that was treated orally. In our experimental series, 5-fluorouracil (5-FU), N-(2-tetrahydrofuryl)-5-fluorouracil (FT-207), carbazilquinone (CQ), vincristine (VCR) and cis-diamminedichloroplatinum (CDDP) were effective in inhibiting the incidence of bladder tumor, however, adriamycin (ADM), mitomycin C (MMC), neocarsinostatin (NCS), cyclophosphamide (CPM) and bleomycin (BLM) were not effective.

Scanning electron microscopy of changes in the urinary bladder in dogs treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN).

SummaryThe fine structures of the bladder mucosa during BBN carcinogenesis and of bladder tumors induced by BBN in dogs were examined by scanning electron microscopy. Normal dog bladder mucosa was covered with polygonal superficial cells with peaked microridges, but no microvilli. Microridges and uniform microvilli were observed in hyperplastic mucosa. In low grade papillary tumors induced by low doses of BBN, pleomorphic microvilli predominated. In dogs which received high doses of BBN, bizarre pleomorphic microvilli and blebs were observed in papillary lesions, whereas bumpy surfaces with thick short microvilli were observed in non-papillary lesions. These sequential changes which were observed in dog bladder mucosa during BBN carcinogenesis parallelled the changes that occurred in the process of chemical carcinogenesis in rodents, and dog bladder tumors were similar to those of rodents and of human bladder cancers.

Rat urinary bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine and N-methyl-N-nitrosourea

SummaryThe present investigation was conducted to examine the combination effect of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) and N-methyl-N-nitrosourea(MNU) in rat urinary bladder carcinogenesis. Experiment 1 was performed in the groups treated by oral BBN administration in combination with MNU intraversical instillation and their control groups. In the groups given both BBN and MNU, the ratio of rats with the nonpapillary type to carcinoma-bearing rats was significantly higher than in the controls. Since most of the carcinomas were non-invasive, the observation period was prolonged in the groups given both BBN and MNU in experiment 2. However, even after a longer observation period, no invasive carcinoma was observed. These results suggest that high-grade and invasive carcinomas similar to those induced by BBN and MNU in the heterotopically transplanted rat bladder cannot be induced in the natural bladder of the rat.

Neoadjuvant Therapy for Locally Invasive Bladder Cancer

The present investigation was conducted to examine the effect of neoadjuvant PVB and CAP regimens for locally invasive bladder cancer and consisted of two studies: (1) a retrospective nonrandomized study of neoadjuvant PVB therapy, and (2) a well-controlled randomized study of neoadjuvant CAP therapy. A total of 25 patients with primary locally invasive bladder cancer were entered into the PVB study between January 1981 and December 1985. Since 1986, 31 patients have been randomized into the CAP study. In the PVB-treated group, a 71.4% complete response (CR) plus partial response (PR) rate and a 71.4% downstaging were noted. On the other hand, in the CAP-treated group, a 50.0% CR plus PR rate and a 88.9% downstaging were noted. The 2- and 5-year survival rates of neoadjuvant PVB were 78.6 and 60.6%, respectively. In contrast, the 2-year survival rate of the neoadjuvant CAP-treated group was 100% at a mean follow-up of 15.8 months. No statistical significance was achieved in the survival rates. These results indicated that neoadjuvant PVB and CAP would be useful in the management of invasive bladder cancer.