Development of Urinary Bladder Pre-Neoplasia by Schistosoma haematobium Eggs and Chemical Carcinogen in Mice

Schistosoma haematobium is a biocarcinogen of human urinary bladder (UB). The present study investigated developing UB cancer mouse model by injecting S. haematobium eggs into the bladder wall and introduction of chemical carcinogens. Histopathological findings showed mild hyperplasia to epithelial vacuolar change, and high grade dysplasia. Squamous metaplasia was observed in the S. haematobium eggs+NDMA group at week 12 but not in other groups. Immunohistochemistry revealed significantly high expression of Ki-67 in urothelial epithelial cells of the S. haematobium eggs+BBN group at week 20. The qRT-PCR showed high expression of p53 gene in S. haematobium eggs group at week 4 and S. haematobium eggs+BBN group at week 20. E-cadherin and vimentin showed contrasting expression in S. haematobium eggs+BBN group. Such inverse expression of E-cadherin and vimentin may indicate epithelial mesenchymal transition in the UB tissue. In conclusion, S. haematobium eggs and nitrosamines may transform UB cells into squamous metaplasia and dysplasia in correlation with increased expression of Ki-67. Marked decrease in E-cadherin and increase in p53 and vimentin expressions may support the transformation. The present study introduces a promising modified animal model for UB cancer study using S. haematobium eggs.

Anticancer Effect of Magnolia officinalis' Extract on N-butyl-N-(4-hydroxybutyl) Nitrosamine Induced Bladder Cancer in Mice / 대한비뇨기과학회지

PURPOSE: Magnolia officinalis has been used in traditional Chinese medicine to treat a variety of diseases. The main constituents of Magnolia officinalis are honokiol and magnolol, which have a variety of pharmacological effects, such as antitumor, antioxidant, antimicrobial, anti-inflammatory etc. This study examined the anticancer effect of a Magnolia officinalis' extract on urinary bladder cancer in vivo. MATERIALS AND METHODS: Male mice C3H/He were used as the experimental animals. The mice were divided into ten groups. Normal drinking water was provided to group 1(5 mice) for 20 weeks and 0.05% N-butyl- N-(4-hydroxybutyl) nitrosamine(BBN) was added to in the drinking water of group 2(5 mice). 0.1, 0.3, 1.0 and 3.0% Magnolia officinalis' extract was added to groups 3, 4, 5 and 6, respectively(5 mice each), and 0.1, 0.3, 1.0 and 3.0% Magnolia officinalis' extract plus 0.05% BBN was added to groups 7, 8, 9 and 10, respectively(10 mice each) for the same period. All surviving mice were sacrificed at week 20 to investigate the occurrence of bladder cancer, stage and grade. RESULTS: Bladder cancer was not observed in groups 1, 3, 4, 5 and 6 mice. The rates of bladder cancer occurrence were 57.1, 66.7, 44.4 and 20.0% in groups 7, 8, 9 and 10, respectively. The incidence decreased with increasing concentration of Magnolia officinalis (p=0.005). However, the stage and grade were not associated with the concentration of Magnolia officinalis(each p>0.05). CONCLUSIONS: This study showed that Magnolia officinalis has some protective effect against bladder cancer. In the future, Magnolia officinalis may be expected to play an important role as a chemo-preventive and therapeutic agent or as a complementary agent in bladder cancer.

The Effects of Intravesical BCG Instillation on Bladder Cancer Induced by N-butyl-N-(4-hydroxybutyl) Nitrosamine / 대한비뇨기과학회지

PURPOSE: We investigate the effects of intravesical BCG therapy on the occurance of superficial bladder cancer induced by N-butyl-N-(4-hydroxybutyl) nitrosamine(BBN) in Fisher 344 rats in vivo. We also examine whether NO mediated the antitumor activity of BCG against superficial bladder cancer in Fisher 344 rats. MATERIALS AND METHODS: BBN(0.1%) is orally administered for 20 weeks and it is combined with BCG(0.27mg) or NG-monomethyl-L-arginine (NG MMA, 10mg). once every week from 8th week to 19th week. The rats are sacrified at 20th week. NO secretion in urine for 24 ours is significantly increased in the BCG treated rats compared to the animals treated with saline or NGMMA. RESULTS: Pathologic findings demonstrate that the incidence of carcinoma is not statistically different in saline, BCG, NGMMA(p>0.05). However the size and number of tumor is decreased in the BCG treated rats compared with saline or NGMMA treated rats bearing bladder cancer induced by BBN(p<0.05). Inducible NO synthase(iNOS) is strongly induced in bladder tissue of rats treated with BCG and NGMMA but not in saline. CONCLUSIONS: Intravesical instillation of BCG on bladder cancer induced by BBN does not decrease the cancer occurrence but reduces the number and size of bladder cancer. Our results suggest that nitric oxide induced by intravesical instillation of BCG may mediate antitumor activity against the occupance of superficial bladder cancer.

Experimental Study on Hyperplasia of Urinary Bladder Epithelium Induced by N-Butyl-N-(4-Hydroxybutyl) Nitrosamine in Rats / 대한비뇨기과학회지

Hyperplasia of the uninary bladder epithelium in Wistar strain female rats after administration of 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine(BBN) was examined histologically and the effect of fat diet on the development of hyperplasia of the urinary bladder was studied. Hyperplasia of the urinary bladder epithelium was consistently observed after 4 weeks, and its extent increased with the period of BBN administration. Some of the hyperplastic lesion, showed a tendency to regress following removal of the carcinogenic stimuli. High fat diet has no effect on hyperplastic change of the urinary bladder in rats.

Ultrastructural Observations on Epithelial Changes of the Urinary Bladder in Rats Induced by N-Butyl-N-(4-Hydroxybutyl) Nitrosamine / 대한비뇨기과학회지

Sequential epithelial changes of the urinary bladder in rats induced by N-butyl-N-(4-hydroxybutyl) nitrosamine(BBN) were studied by means of transmission electron microscopy. 0.05% BBN was administered orally in Wistar strain rats for 4 to 12 weeks and sacrificed at the 4th to 20th week. The urinary bladder epithelial changes were classified into 4 categories by conventional light microscopic criteria; normal transitional epithelium, mucosal epithelial hyperplasia, transitional epithelial papilloma and transitional cell carcinoma. The ultrastructural characteristics of the urinary bladder epithelium in rats induced by BBN are as follows; 1. General cellular appearances corresponded to a gradual sequential changes from hyperplasia to carcinoma, and the basement membrane became uneven and/or incomplete in carcinoma. 2. Irregularity of nuclear configurations was proportionally increased together with nuclear membranes and chromatin. 3. Development of intercellular infoldings and desmosomes was much irregular and marked in the neoplastic lesions. 4. Alterations of subcellular organelles began to appear from the hyperplastic epithelium, and also were reflected by increased number of tonofibrils and desmosomal changes according to the degree of malignant potentiality.