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1.
Journal of Biomedical Engineering ; (6): 552-555, 2013.
Article in Chinese | WPRIM | ID: wpr-234613

ABSTRACT

This study was aimed to establish rat bladder tumor animal models to investigate the in viva antitumor effect of polyanhydride-pirarubicin (PAD-THP), a long-lasting anti-cancer implant, in the bladder tumor of animal models. The model of bladder cancer was set up with N-butly-N-(4 hydroxybutyl) nitrosamine (BBN) feeding into rats. The PAD-THP long-acting anti-cancer implants containing the drugs and the same dose of the THP naked drug were placed under the bladder mucosa of bladder tumor model in vivo. The pirarubicin plasma concentration was measured with high performance liquid chromatography (HPLC) detection in vivo. The effective drug concentration and lasting period were observed and compared in the animal bodies. The tumor sizes were measured before and after the treatment. The in viva antitumor effects were analyzed and compared. The results showed that more significant antitumor effect of PAD-THP implants on the local drug release characteristics were presented compared with that of the same dose of THP bare drug group and there were significant differences (P<0. 05) between the two methods. All the results indicated that the PAD-THP anti-cancer implants in the postoperative local treatment of bladder tumors would show prosperous in the future for clinical application.


Subject(s)
Animals , Female , Rats , Antineoplastic Agents , Butylhydroxybutylnitrosamine , Delayed-Action Preparations , Disease Models, Animal , Doxorubicin , Implants, Experimental , Polyanhydrides , Rats, Sprague-Dawley , Urinary Bladder Neoplasms , Drug Therapy , Pathology
2.
Acta cir. bras ; 27(8): 529-536, Aug. 2012. ilus, tab
Article in English | LILACS | ID: lil-643620

ABSTRACT

PURPOSE: To determine the effects of water-soluble derivative of green propolis in bladder cancer angiogenesis in rats given N-butyl-(-4-hydroxybutyl) nitrosamine (BBN). METHODS: Nine groups were established, where six of them (Groups 1 to 6), the animals received 0.05% BBN in their drinking water for 14 weeks. From the 32nd to the 40th week, Groups 1, 2, 3 and 4 were treated respectively with water, L-lysine (300 mg/kg/day), celecoxib (30 mg/kg/day) and propolis (300 mg/kg/day). Groups 5 and 6 were given propolis and L-lysine from the 1st to the 40th week (150 mg/kg/day). Microvascular density was determined by histological sections stained for the marker CD-31 and analyzed with specific software. RESULTS: The microvascular density in bladder carcinomas was lower (p<0.01) in rats receiving propolis than in controls given carcinogen only. On the other hand, the microvascular density of tumors in rats receiving carcinogen and L-lysine for 40 weeks from the beginning of carcinogen treatment was significantly higher (p<0.01) than in the corresponding controls. CONCLUSION: Water-soluble derivative of propolis inhibits angiogenesis in BBN-induced rat bladder cancer, while L-lysine treatment stimulates angiogenesis if initiated concurrently with BBN.


OBJETIVO: Determinar os efeitos da própolis verde solúvel em água na angiogênese de câncer de bexiga em ratos que receberam n-butil-(-4-hidroxibutil) nitrosamina (BBN). METODOS: Nove grupos foram estabelecidos, onde em seis destes (grupos de 1 a 6) os animais receberam BBN a 0,05% em água de beber por 14 semanas. Na 32ª semana das 40 semanas, os grupos 1, 2, 3 e 4 foram tratados respectivamente com água, L lisina (300 mg/kg/dia), celecoxibe (30 mg/kg/dia) e própolis (300 mg/kg/dia). Os grupos 5 e 6 receberam própolis e L lisina da 1ª a 40ª semana (150 mg/ kg/dia). A densidade microvascular foi determinada por cortes histológicos corados pelo CD-31 e analisados por programa de computador específico. RESULTADOS: A densidade microvascular em carcinomas de bexiga foi menor com p<0,01 nos ratos que receberam própolis do que nos carcinomas do grupo controle que recebeu apenas carcinógeno. Por outro lado, a densidade microvascular de tumores de ratos que receberam carcinógeno e L-Lisina por 40 semanas desde o início do carcinógeno foi significantemente maior com p<0,01 que a densidade microvascular dos tumores de seu respectivo grupo controle. CONCLUSÃO: A própolis verde solúvel em água inibiu a angiogênese em câncer de bexiga induzido pelo BBN, enquanto a L- lisina estimulou a angiogênese quando iniciada juntamente com o BBN.


Subject(s)
Animals , Female , Rats , Angiogenesis Inhibitors/therapeutic use , Butylhydroxybutylnitrosamine/therapeutic use , Carcinoma/drug therapy , Lysine/therapeutic use , Neovascularization, Pathologic/drug therapy , Propolis/therapeutic use , Urinary Bladder Neoplasms/drug therapy , Carcinoma/pathology , Disease Models, Animal , Neovascularization, Pathologic/pathology , Plant Extracts/therapeutic use , Rats, Wistar , Time Factors , Treatment Outcome , Urinary Bladder Neoplasms/blood supply , Water/chemistry
3.
Acta cir. bras ; 27(2): 185-192, Feb. 2012. ilus, tab
Article in English | LILACS | ID: lil-614540

ABSTRACT

PURPOSE: To determine the effects of green propolis extracted in L-lysine (WSDP) and of L- lysine for 40 weeks on induced rat bladder carcinogenesis. METHODS: The animals (groups I, II, III, IV, V and VI) received BBN during 14 weeks. Group I was treated with propolis 30 days prior received BBN, and then these animals were treated daily with propolis; Groups II and III was treated with subcutaneous and oral propolis (respectively) concurrently with BBN. The animals of Group IV were treated L-lysine; Group V received water subcutaneous; and Group VI received only to BBN. Among the animals not submitted to carcinogenesis induction, Group VII received propolis, Group VIII received L-lysine and Group IX received water. RESULTS: The carcinoma incidence in Group I was lower than that of control (Group VI). The carcinoma multiplicity in Group IV was greater than in Group VI. All animals treated with L-lysine developed carcinomas, and they were also more invasive in Group IV than in controls. On the other hand, Group VIII showed no bladder lesions. CONCLUSION: The WSDP is chemopreventive against rat bladder carcinogenesis, if administered 30 days prior to BBN , and that L-lysine causes promotion of bladder carcinogenesis.


OBJETIVO: Determinar os efeitos da própolis verde extraída em L - Lisina (WSDP) e da L-Lisina por 40 semanas em ratos induzidos a carcinogênese de bexiga. MÉTODOS: Os animais (grupos I, II, III, IV, V e VI) receberam BBN por 14 semanas. O grupo I foi tratado com própolis 30 dias antes de receber BBN e em seguida estes animais foram tratados diariamente com própolis; Os grupos II e III foram tratados com própolis subcutânea e oral (respectivamente) e concorretemente com BBN. Os animais do grupo IV foram tratados com L- Lisina; o grupo V recebeu água subcutânea; o grupo VI recebeu apenas BBN. Entre os animais não submetidos a indução de carcinogênese, Grupo VII, receberam própolis, Grupo VIII, receberam L-Lisina e Grupo IX receberam água. RESULTADOS: A incidência de carcinoma no grupo I foi menor que no grupo controle (grupo IV) A multiplicidade de carcinoma no grupo IV foi maior que no grupo VI. Todos os animais tratados com L - Lisina desenvolveram carcinomas e estes foram mais invasivos no grupo IV que no grupo controle. Por outro lado o grupo VIII não apresentou lesões. CONCLUSÃO: WSDP é quimiopreventiva contra a carcinogese de bexiga se administrada 30 dias antes do início do BBN, e a L - Lisina causa promoção da carcinogênese de bexiga.


Subject(s)
Animals , Female , Rats , Butylhydroxybutylnitrosamine/therapeutic use , Lysine/pharmacology , Plant Extracts/therapeutic use , Propolis/therapeutic use , Urinary Bladder Neoplasms/prevention & control , Anticarcinogenic Agents/pharmacology , Anticarcinogenic Agents/therapeutic use , Carcinogens , Plant Extracts/pharmacology , Propolis/pharmacology , Rats, Wistar , Time Factors , Treatment Outcome , Urinary Bladder Neoplasms/chemically induced , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology
4.
Article in English | IMSEAR | ID: sea-37936

ABSTRACT

Potential inhibitory effects of the antiangiogenic drug TNP-470 on rat urinary bladder carcinogenesis were investigated in F344 male rats initiated with 0.05% BBN in the drinking water for 8 weeks. Group 1 was then continuously treated with TNP-470 by subcutaneous injection using osmotic minipump until the end of the experiment; group 2 served as the control with only initiation. The incidences and multiplicities of papillomas and carcinomas in the TNP-470-treated group were significantly decreased compared to the control group values along with the tumor vascular density. In conclusion, TNP-470 can inhibit rat urinary bladder carcinogenesis, presumably through its effects on angiogenesis.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Animals , Biopsy, Needle , Blotting, Northern , Butylhydroxybutylnitrosamine , Chi-Square Distribution , Cyclohexanes , Dose-Response Relationship, Drug , Drug Administration Schedule , Immunohistochemistry , Male , Neoplasms, Experimental , Neovascularization, Pathologic/prevention & control , Probability , RNA, Messenger/analysis , Random Allocation , Rats , Rats, Inbred F344 , Sensitivity and Specificity , Sesquiterpenes/pharmacology , Urinary Bladder Neoplasms/drug therapy , Vascular Endothelial Growth Factor A/analysis
5.
Korean Journal of Urology ; : 310-315, 2006.
Article in Korean | WPRIM | ID: wpr-56096

ABSTRACT

PURPOSE: Cyclooxygenase (COX)-2 plays an important role in promoting cancer cell proliferation and angiogenesis in human bladder cancer. In this study, we investigated the antitumor or antiangiogenic effects of selective COX-2 inhibitor on N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced rat bladder tumorigenesis. MATERIALS AND METHODS: Forty male Fischer 344 rats (control) were given only 0.05% BBN, while 40 rats (experimental) were administered 1,500mg/ kg celecoxib once daily and this treatment started from 1 week before their BBN treatment. Ten rats from the control groups and the experimental groups were then sacrificed at 4, 12, 16 and 24 weeks after BBN treatment. We observed all the bladders macroscopically as well as microscopically, and we measured the COX-2 expression in the bladder tissues. Utilizing a cDNA microarray, we analyzed the significant differences of gene expression between the 12 week-control group and the 12 week-experimental group. RESULTS: The incidence of tumor was lower in the experimental group than in the control group from week 12 to week 24. The COX-2 expressions were more significantly decreased via the BBN induction (p<0.05) in the experimental groups than in the control groups after 4 weeks. For the 12 week-experimental group, there were 15 genes altered by the administration of selective COX-2 inhibitor, and the selective COX-2 inhibitor especially regulated transgelin, membrane metallo endopeptidase and apolipoprotein E of these 15 genes to prevent the incidence of bladder tumor. CONCLUSIONS: Selective COX-2 inhibitor has an inhibitory effect on BBN-induced rat bladder tumorigenesis. In the pre-neoplastic phase, selective COX-2 inhibitor regulates transgelin, membrane metallo endopeptidase and apolipoprotein E to prevent the incidence of bladder tumor.


Subject(s)
Animals , Humans , Male , Rats , Angiogenesis Inducing Agents , Apolipoproteins , Butylhydroxybutylnitrosamine , Carcinogenesis , Cell Proliferation , Cyclooxygenase 2 , Gene Expression , Incidence , Neprilysin , Oligonucleotide Array Sequence Analysis , Prostaglandin-Endoperoxide Synthases , Transcriptome , Urinary Bladder Neoplasms , Urinary Bladder , Celecoxib
6.
Korean Journal of Pathology ; : 333-338, 2006.
Article in Korean | WPRIM | ID: wpr-42303

ABSTRACT

BACKGROUND: Survivin belongs to the inhibitor of apoptosis family, and it has recently been found to be expressed in most solid tumors. Therefore, its expression is suggested to have prognostic significance. However, no data are available concerning the significance of survivin for the carcinogenesis of bladder cancer. METHODS: In order to induce urothelial tumor in the rat urinary bladder, 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was administered to male Sprague-Dawley rats for 30 weeks. We used immunohistochemistry to investigate the expressions of survivin, HSP90, Bcl-2 and Bax in rat bladder carcinogenesis. RESULTS: Urothelial cell hyperplasia, papilloma, non-invasive urothelial carcinoma and invasive urothelial carcinoma appeared at 5, 10, 20 and 30 weeks, respectively. The expressions of survivin and HSP90 increased sequentially from normal mucosa, hyperplasia, papilloma, non-invasive urothelial carcinoma to invasive urothelial carcinoma. The expressions of Bcl-2 and Bax did not increase, however the number of cases with more than 1 of Bcl-2/Bax expression ratio increased sequentially during the progression of urothelial lesion. The expression of survivin showed a statistically significant correlation with the expression of HSP90 and the Bcl-2/Bax expression ratio. CONCLUSIONS: Our findings suggest that survivin may be involved in the carcinogenesis of rat bladder and its expression is correlated with the expression of HSP90 and the Bcl-2/Bax expression ratio.


Subject(s)
Animals , Humans , Male , Rats , Apoptosis , bcl-2-Associated X Protein , Butylhydroxybutylnitrosamine , Carcinogenesis , Hyperplasia , Immunohistochemistry , Mucous Membrane , Papilloma , Rats, Sprague-Dawley , Urinary Bladder Neoplasms , Urinary Bladder
7.
Korean Journal of Urology ; : 578-584, 2004.
Article in Korean | WPRIM | ID: wpr-109239

ABSTRACT

PURPOSE: Cyclooxygenase-2 (COX-2) plays an important role in promoting cancer cell proliferation and angiogenesis in human bladder cancer. The selective COX-2 inhibitor has antitumor activities in vivo and in vitro in a variety of tumor types. In this study, the antitumor or antiangiogenic effects of selective COX-2 inhibitor on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced rat bladder tumorigenesis were investigated. MATERIALS AND METHODS: Forty male Fischer 344 rats (Control group) were given only 0.05% BBN in water ad libitum, while 40 others (Experimental group) were administered 1,500mug/kg celecoxib once daily through the gavage tube, which started 1 week before the BBN treatment. Ten rats were used as the normal bladder. Ten rats from the control and experimental group were sacrificed 4, 12, 16, and 24 weeks after the start of the BBN treatment. All bladders were evaluated both macroscopically and microscopically. We also measured COX-2 expression, microvessel density (MVD), and vascular endothelial growth factor (VEGF) protein concentrations in the bladder tissues. RESULTS: Macroscopically and microscopically, the incidence of tumor was lower in the experimental group than in the control group from the 12th week to the 24th week. Each incidence of tumor in week 12, week 16, and week 24 was 20%, 50%, and 80% in the control group and 0%, 20%, and 40% in the experimental group, respectively. In both the control and experimental groups, COX-2 expression had a tendency to be concentrated in the cytoplasm of the epithelial cells of the papillary tumor and the endothelial cells adjacent to the vessel the basal layer of bladder. COX-2 and VEGF expression were significantly more decreased in the experimental groups than in the control groups after 4 weeks from the BBN induction (p<0.05). MVD was significantly decreased in the experimental group at week 16 (p<0.05). CONCLUSIONS: The selective COX-2 inhibitor has an inhibitory effect on BBN-induced rat bladder tumorigenesis because of its partially antiangiogenic properties. In the future, the selective COX-2 inhibitor could be expected to play an important role as a chemo-preventive agent and as therapeutic aids in bladder cancer if these inhibitory effects can be reproduced in human bladder tumorigenesis.


Subject(s)
Animals , Humans , Male , Rats , Angiogenesis Inducing Agents , Butylhydroxybutylnitrosamine , Carcinogenesis , Cell Proliferation , Cyclooxygenase 2 , Cytoplasm , Endothelial Cells , Epithelial Cells , Incidence , Microvessels , Urinary Bladder Neoplasms , Urinary Bladder , Vascular Endothelial Growth Factor A , von Willebrand Factor , Water , Celecoxib
8.
Korean Journal of Urology ; : 177-183, 1992.
Article in Korean | WPRIM | ID: wpr-66278

ABSTRACT

It is known that the activity of tumor cells correlates with the malignant potential of tumors. Nucleolar organizer regions(NORs) are loops of DNA which occur in nucleoli and which possess ribosomal DNA genes. Ribosomal DNA genes transcribe to ribosomal RNA by RNA polymerase I and are of vital significance in the ultimate synthesis of protein. Proteins associated with the NORs are stained with silver nitrate(Ag-NORs). Ag-NORs were studied in various tumors and might reflect the activity of cells and might be and indicator of the degree of malignancy in tumors. 0.05 % N-Butyl-N(4-hydroxybutyl) nitrosamine(BBN) in drinking water was given for 8 and 14 weeks to induce pre-neoplastic and neoplastic vesical epithelial lesions in female Wister rats. Ag-NORs were stained by the simple one-step silver colloid staining in routine processed, formalin-fixed paraffin sections of bladder lesions induced by N-butyl-N(4-hydroxybutyl) nitrosamine(BBN) in rat. The mean number of silver stained NORs(Ag-NORs) was as follows : normal transitional epithelium was 1.64+/-0.25(mean+/-SD; n=10), simple hyperplasia was 2.24+/-0.24(n=7). nodular hyperplasia was 2.63+/-0.12 (n=6), transitional cell papilloma was 3.24+/-0.28(n=6) and transitional cell carcinoma was 4.52+/-0.32(n=10). Based on the above results, we concluded that the mean number of Ag-NORs showed a stepwise increase from normal transitional epithelium through simple hyperplasia and nodular hyperplasia to papilloma and carcinoma of bladder epithelium induced by BBN in rat and may reflect proliferative activity of cells. Further investigations may be needed to confirm whether the number or quantification of Ag-NORs is a useful method for evaluating proliferative activity of neoplastic lesions or another indicator of prognosis in human bladder cancer.


Subject(s)
Animals , Female , Humans , Rats , Butylhydroxybutylnitrosamine , Carcinoma, Transitional Cell , Colloids , DNA , DNA, Ribosomal , Drinking Water , Epithelium , Hyperplasia , Nucleolus Organizer Region , Papilloma , Paraffin , Prognosis , RNA Polymerase I , RNA, Ribosomal , Silver , Urinary Bladder Neoplasms , Urinary Bladder
9.
Korean Journal of Urology ; : 583-587, 1992.
Article in Korean | WPRIM | ID: wpr-92153

ABSTRACT

N-buty1-N-(4-hydroxybutyl)nitrosamine(BBN) is known to have a strong. specific carcinogenic action on the urinary bladder of rats. Rat bladder lesions induced by BBN are very similar to those of Pusan histopathologically. To investigate the surface change in the urinary bladder epithelium induced by 0.05% BBN scanning electron microscopic examination was done. Normal bladder epithelium was formed by relatively uniform sized. flat polygonal cells and clearly defined with intercellular ridges. in high magnification, the luminal surface of superficial cell consisted of hexagona1 areas and concave plaques between microridge giving a honeycomb appearance but no microvilli was visible. On BBN administration for 12 weeks, the superficial cells varied in size and shape and covered by numerous uniform round microvilli forming cobble stone appearance. On BBN administration for 12 weeks and water for 6 weeks, the superficial cells were covered with numerous microvilli completely. In some areas numerous pleomorphic microvilli were seen. Although pleomorphic microvilli are not a specific marker for neoplastic transformation, their presence is an indicator. of a markedly abnormal proliferative response.


Subject(s)
Animals , Rats , Butylhydroxybutylnitrosamine , Epithelium , Microscopy, Electron, Scanning , Microvilli , Phenobarbital , Urinary Bladder , Water
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