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PubMed1981

Influence of total dose and dose schedule on induction of urinary bladder cancer in the mouse by N-butyl-N-(4-hydroxybutyl)nitrosamine.

Dose-response relationships in the induction of urinary bladder cancer in male C57BL/6 x DBA/2-F1 (BDF) mice by intragastric instillation of N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN) were studied. Administration of a total dose of 0 to 80 mg OH-BBN in 10 weekly fractions to groups of 25 mice resulted in a linear increase in carcinoma incidence with dose. OH-BBN administration schedule had a significant effect on cancer incidence: administration of a total dose of 30, 20, or 15 mg OH-BBN in 20 weekly fractions was more effective in cancer induction than was the same total dose given in 5 fractions. A 10 dose administration schedule was of intermediate efficacy. The data obtained indicate that OH-BBN induces urinary bladder cancers in BDF mice in a dose-related manner, with high target organ-specificity, little toxicity, and short tumor latency; induced tumors are primarily transitional cell carcinomas which morphologically resemble their human counterpart. Administration of OH-BBN mice provides a useful model for the experimental study of urinary bladder cancer.

Animals↗
PubMed2003

Impact of Gemcitabine and Cisplatin with radiotherapy in locally advanced or metastatic transitional cell carcinoma of urinary bladder.

OBJECTIVE: The primary object of this study is to evaluate the efficacy and safety of Gemcitabine and Cisplatin along with radiotherapy in transitional cell carcinoma of urinary bladder. PATIENTS AND METHODS: Twenty patients with locally advanced or metastatic TCC of urinary bladder were enrolled during the 22-months period from January, 1999 to October, 2000 and followed up till March 2002. Three patients received 4 cycles, five patients received 5 cycles and twelve patients received 6 cycles of Gemcitabine 1250 mg/m2 on day 1 and day 8 and Cisplatin 80 mg/m2 on day 1; administered every 3 weeks. No patient received prior chemotherapy, radiotherapy or surgery. However, four patients received prior intravesical chemotherapy. All patients received radiotherapy after completion of chemotherapy regimen. RESULTS: Nineteen patients achieved complete response at the end of the treatment. The complete response rate was 95%. The confidence interval was at 95%, level of confidence ranged from 85% to 100%. Median duration of clinical benefit was 21 months. Six patients (30%) were documented neutropenia, three patients (15%) documented thrombocytopenia. No life threatening toxicity was observed. CONCLUSION: Gemcitabine and Cisplatin along with radiotherapy in locally or metastatic Transitional cell carcinoma of urinary bladder, exhibited pronounced response rate among all the patients. The toxicity profile remained extremely low and disease free survival enhanced. The above investigation may further be continued at a larger scale encompassing a wide band of subjects.

Aged↗
PubMed1989

Cell cycle dependence of N-methyl-N-nitrosourea-induced tumour development in the proliferating, partially resected rat urinary bladder.

In the present experiments the dependence of tumour induction upon the different phases of the cell cycle in the proliferating urinary bladder was examined. For stimulation of urothelial proliferation, a one-third resection of the bladder was performed in female Wistar rats. To synchronize the proliferating urothelial cells, hydroxyurea (HU) was given in 23 fractionated, consecutive intraperitoneal doses (0.1 mg/g body weight each) at hourly intervals shortly prior to and during maximal proliferation (between 33 and 55 h following partial cystectomy). The direct-acting urothelial carcinogen N-methyl-N-nitrosourea (MNU) was administered as a single, intravesicular pulse dose (5 mg/kg body weight) during the different cell cycle phases and to control animals with a non-resected, quiescent bladder (G0-phase). The incidence of urothelial bladder tumours was 32.6% in the controls. By comparison, the tumour incidences were 18.9, 9.3, 21.7, 26.3, 25.0 and 30.0%, respectively, when MNU was instilled during the late G1-, early and late S-, G2 + M-, and the early and late postmitotic phase. The results obtained from a total of 283 rats thus clearly document a cell-cycle-specific inhibition of MNU-induced tumour development in the proliferating urinary bladder, particularly when the carcinogen was administered during the early S-phase (P less than 0.016). There were no differences in the histology and extension of the urothelial bladder tumours found in the different experimental groups. MNU has also been shown to produce urothelial tumours in the renal pelvis (overall tumour incidence: 3.2%) and ureters (1.4%) as well as mesenchymal tumours in the bladder (4.9%) and kidneys (1.4%). Conclusions are tentatively drawn about the mechanisms underlying the observed cell-cycle-specific inhibition of urothelial carcinogenesis.

Animals↗
PubMed2003

Primitive neuroectodermal tumor (PNET) of the urinary bladder.

We report on the clinical, morphologic, immunohistochemical, ultrastructural, and molecular cytogenetic features of a primitive neuroectodermal tumor (PNET) primarily arising in the urinary bladder. An 81-year-old man presented with lymphedema of the lower extremities, fatigue, and urge incontinence. Radiographically, a tumor filling the entire cavity of the urinary bladder and extending into the pelvic and retroperitoneal tissue was noted. Histology of tumor biopsies showed a highly cellular, focally necrotic small round-cell tumor with numerous mitoses and occasional rosette-like structures. The tumor cells displayed significant immunoreactivity for neuron-specific enolase (NSE) and the MIC2 gene product (CD99). Dense-core granules were detectable by electron microscopy. A molecular cytogenetic analysis using comparative genomic hybridization (CGH) revealed gains of the chromosomes 3p, 6, 8q, 12, 17q, and 21q. The patient died two weeks after diagnosis. To the best of our knowledge, this is the fifth reported case of a PNET of the urinary bladder, and the first that includes a molecular cytogenetic analysis based on CGH.

12E7 Antigen↗
PubMed1997

Chemopreventive efficacy of piroxicam administered alone or in combination with lycopene and beta-carotene on the development of rat urinary bladder carcinoma after N-butyl-N-(4-hydroxybutyl)nitrosamine treatment.

The effects of the non-steroidal anti-inflammatory drug (NSAID) piroxicam and the carotenoids lycopene and beta-carotene, alone or in combination, on the development of rat superficial urinary bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were studied. Male Fischer 344 rats, 6 weeks old, were given 0.05% BBN in the drinking water for 8 weeks followed by administration of piroxicam (0.0075% in the diet), lycopene (0.0025% in the drinking water) and/or beta-carotene (0.0025% in the drinking water) for 12 weeks, then killed for histological analysis of urinary bladder lesions. Cell proliferation potential was analyzed by immunohistochemical staining of the proliferative cell nuclear antigen (PCNA). Piroxicam alone, piroxicam+lycopene, and piroxicam +lycopene+ beta-carotene all significantly decreased the incidences and numbers of transitional cell carcinomas (TCCs), but the combination of piroxicam with carotenoids did not result in a clear improvement in the preventive potential of piroxicam. Piroxicam+ beta-carotene also caused a significant reduction and lycopene alone a slight but not significant reduction in the number of TCCs. In contrast, beta-carotene alone and lycopene+ beta-carotene were without inhibitory influence on any of the lesion categories examined, and the latter significantly increased the proportion of high-grade TCCs. Nevertheless, all of the chemopreventive agents, either alone or in combination, significantly decreased the TCC PCNA index, the effect extending to the surrounding epithelium in the piroxicam+lycopene and piroxicam+lycopene+beta-carotene groups. These results indicate that the NSAID piroxicam may be a more effective chemopreventive agent than lycopene and beta-carotene for superficial urinary bladder carcinogenesis.

Animals↗
PubMed2000

DNA damage induced by 3,3'-dimethoxybenzidine in liver and urinary bladder cells of rats and humans.

3,3'-Dimethoxybenzidine (DMB), a congener of benzidine used in the dye industry and previously found to be carcinogenic in rats, was evaluated for its genotoxic activity in primary cultures of rat and human hepatocytes and of cells from human urinary bladder mucosa, as well as in liver and bladder mucosa of intact rats. A similar modest dose-dependent frequency of DNA fragmentation was revealed by the alkaline elution technique in metabolically competent primary cultures of both rat and human hepatocytes exposed for 20 h to subtoxic DMB concentrations ranging from 56 to 180 microM. Replicating rat hepatocytes displayed a modest increase in the frequency of micronucleated cells after a 48-h exposure to 100 and 180 microM concentrations. In primary cultures of human urinary bladder mucosa cells exposed for 20 h to 100 and 180 microM DMB, the Comet assay revealed a clear-cut increase of DNA fragmentation. In rats given one-half LD50 of DMB as a single oral dose, the GSH level was reduced in both the liver and urinary bladder mucosa, whereas DNA fragmentation was detected only in the bladder mucosa. Taken as a whole, these results suggest that DMB should be considered a potentially genotoxic chemical in both rats and humans; the selective effect on the rat urinary bladder might be the consequence of pharmacokinetic behavior.

Administration, Oral↗
PubMed1986

A double-blind randomized comparison of the effect and tolerance of Varidase versus saline when instilled in the urinary bladder in patients with catheter problems.

Thirty-eight patients with problems with their urinary catheters were randomly treated with Varidase or normal saline solution once a day for 10 days. Photographs were taken by using a cystoscope before treatment, at day 10 and day 24 after the commencement of treatment. The photographs were evaluated according to the occurrence of pus, debris, coagula and rubor. In the Varidase group the improvements from baseline to day 10 and day 24 were statistically significant (p less than 0.05) in all parameters while there were no statistically significant improvements in the saline group. Comparing the two treatment groups, regarding the changes from baseline to day 10 and day 24, it was statistically demonstrated that Varidase was significantly more effective than saline in all parameters (p less than 0.05). In conclusion, this study shows that Varidase effectively cleans the urinary bladder from pus, fibrin, necrotic tissue and blood clots.

Aged↗
PubMed1988

A novel type of unmyelinated chemosensitive nociceptor in the acutely inflamed urinary bladder.

Single primary afferents supplying the cat urinary bladder were electrophysiologically recorded in the sacral dorsal roots. Under normal conditions, afferents were not spontaneously active when the bladder was empty and innocuous increases of intravesical pressure excited mainly thin myelinated, low-threshold mechanoreceptors. Less than 2.5% of all unmyelinated visceral afferents responded to a mechanical stimulus, but all had high, presumably noxious thresholds. During an acute inflammation induced with intravesical injections of 2.5% mustard oil or 50-100% turpentine oil both populations developed resting activity and changed their mechanosensitive properties. Out of the many unmyelinated afferents without appreciable mechanosensitivity, an entirely new subpopulation was activated by chemical irritants during an acute inflammation. Subsequently, some of these chemosensitive receptors started to display new mechanosensitive properties. This novel population of sensory neurones may contribute considerably to the pathogenesis of visceral pain states including reflex disturbances of bladder motility.

Action Potentials↗
PubMed1994

Antidiuretic response in the urinary bladder of Xenopus laevis: presence of typical aggrephores and apical aggregates.

The urinary bladder of the aquatic toad Xenopus laevis is known to exhibit a low permeability to water and a poor sensitivity to antidiuretic hormone. In order to precise the characteristics and the specific cellular mechanisms of this reduced hydro-osmotic response we used a sensitive volumetric technique to monitor net water flow and studied the correlation between the antidiuretic hormone (ADH)-induced net water flow and the fine ultrastructural appearance of the urinary bladder epithelium. Transmural net water flow was entirely dependent on the osmotic gradient across the preparation and not on the hydrostatic pressure difference. We observed the existence of a low but significant hydro-osmotic response to arginine vasopressin. Freeze-fracture electron microscopy demonstrated the presence of typical aggrephores in the subapical cytoplasm. The response to the hormone was accompanied by the appearance of typical intramembrane aggregates into the apical plasma membrane. Water permeability increase and apical aggregate insertion were both slowly but fully reversible. Except for the multilayered structure of the epithelium and the particularly low response to antidiuretic hormone, all the studied permeability and ultrastructural characteristics of the bladder were thus very similar to those observed in other sensitive epithelia such as the amphibian bladder and skin and the mammalian collecting duct which exhibit a high hydro-osmotic response to the hormone.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2006

Absence of Epstein-Barr virus infection in squamous cell carcinoma of upper urinary tract and urinary bladder.

OBJECTIVES: To address whether Epstein-Barr virus (EBV) infection may be involved in the carcinogenesis of squamous cell carcinoma of the upper urinary tract and urinary bladder (SCC-UB). EBV has been implicated in the genesis of a variety of human cancers, including urothelial carcinoma of the urinary bladder. METHODS: Whether EBV infection is related to SCC-UB carcinogenesis was investigated by in situ hybridization for EBV-encoded RNA and immunohistochemistry for latent membrane protein-1 in 26 cases of SCC-UB. RESULTS: EBV-encoded RNA and latent membrane protein-1 were identified in the control case of nasopharyngeal carcinoma. None of the SCC-UB cases had a nuclear signal of EBV-encoded RNA, and the cancer cells, normal urothelial cells, and inflammatory cells were all negative for latent membrane protein-1, irrespective of the site of SCC-UB. CONCLUSIONS: This study is the first to explore the role of EBV infection in SCC-UB. Our results suggest that EBV infection is not involved in the carcinogenesis of SCC of the renal pelvis, ureter, and urinary bladder.

Aged↗
PubMed1997

Effect of chloroquine on the contractility of the smooth muscles of the rat uterus, trachea and urinary bladder.

This study was performed to investigate the effect of chloroquine (CQ) on the contractility of isolated smooth muscles of the rat uterus, urinary bladder; and trachea. Chloroquine, 4 x 10(-4) mol.l-1 completely abolished uterine contractions produced by 10(-2) IU/ml oxytocin, and 10(-6) mol.l-1 5-hydroxytryptamine (5-HT) and acetylcholine (Ach). Chloroquine also caused a concentration-dependent relaxation of 10(-6) mol.l-1 Ach-contracted rat trachea. Cumulative addition of CQ (10(-8)-10(-3) mol.l-1) to spontaneously contracting rat urinary bladder did not produce any significant effect. It also did not affect the contractile response of the bladder to Ach and 5-HT. The results suggest that CQ inhibits the contractile process in the rat uterus and trachea but not the urinary bladder.

Animals↗
PubMed1989

Comparative study of urinary bladder carcinomas in Japanese and Egyptians.

One hundred six Japanese and 169 Egyptian cases of urinary bladder carcinoma treated by total cystectomy were analyzed histopathologically. Urinary bladder carcinomas in Egypt were encountered at an earlier age than those in Japan. The proportion of carcinomas in Egyptian males was higher than in Japanese males. Squamous cell carcinomas (SCCs) predominated in Egyptian cases whereas transitional cell carcinomas predominated in Japanese cases. The pathological stage of Egyptian cancers was more advanced than in Japanese cases; even grade 1 SCCs showed invasion into the muscular layer. Most carcinomas in Egypt were associated with Schistosoma haematobium infections.

Aged↗
PubMedDate not supplied

[Nephrureterectomy with endoscopic resection of the urinary bladder, ureteral ostium and terminal part in papillary tumors of the upper urinary tracts].

Short- and long-term results of endoscopically assisted nephrureterectomy were studied in 15 patients (7 males and 8 females aged 31-79 years) with papillary tumours of the upper urinary tracts (UUT). Of them, 11 patients have undergone transurethral endoresection of the urinary bladder, ostium and terminal part of the ipsilateral ureter followed by nephrureterectomy from the lumbotomic approach (technique 1) and 4 patients had nephrureterectomy followed by endoscopic intervention (technique 2). Results of standard open nephrureterectomy with resection of the bladder were analyzed retrospectively for 25 patients with papillary tumors of the UUT taken as control. It was found that transurethral endoscopic resection of the bladder, ostium and terminal part of the ipsilateral ureter in nephrureterectomy for papillary tumors of the UUT facilitates the performance, decreases duration and aggression of surgical intervention, diminishes number of complications, shortens hospital stay of the patients and their rehabilitation. Technique 1 is thought more ablastic and simple in performance.

Adult↗
PubMed1979

Transepithelial current-voltage relationships of toad urinary bladder and colon. Estimates of ENaA and shunt resistance.

Studies were done to investigate the transepithelial current-voltage (IT-VT) relationships of urinary bladder and colon of the toad Bufo marinus. Like several other Na transporting epithelia, the IT-VT plots characteristically showed a break at voltage E1, averaging near 124 mV for urinary bladder and 110 mV for colon. With bladders treated with antidiuretic hormone, estimates of ENa and shunt resistance, Rs, were obtained according to a method outlined by Yonath and Civan, 1971 (J Membr. Biol. 5:336-385). Our results not only confirmed their observations, but were consistent with the notion that the values of E1 (IT-VT plots) were the same as those of ENa. In addition, the values of Rs were found to be the same as those estimated from the quotient E1/I1 obtained from the voltage and current coordinates at the break of the IT-VT plot of bladders studied in both stretched and unstretched states. Amiloride at concentrations up to 10(-5) M caused a small decrease of both E1 and E1/I1 of urinary bladder. Similarly, amiloride caused small but significant changes of ENa and RNa of the colon. For both epithelia, the values of E1 and E1/I1 of the IT-VT plots were the same as those of ENa and Rs estimated by an independent method. In general, these findings are similar to those of several other epithelia where the ENa and Rs can be estimated directly from their IT-VT relationships.

Amiloride↗
PubMed1977

Insulin-mediated Na+ transport in the toad urinary bladder.

The characteristics of insulin-induced Na+ transport in the toad urinary bladder were determined and compared to those of aldosterone. Bladders were mounted in modified Ussing chambers, and standard short-circuit current techniques were employed to measure transepithelial Na+ transport. Insulin added to the serosal medium is much more effective than insulin added to the mucosal medium. Serosal insulin concentrations from 10(1) to 10(3) muU/ml increase both the initial rate and the final level of Na+ transport achieved, whereas concentrations from 10(3) to 10(5) muU/ml increase only the initial rate of Na+ transport. Insulin-induced Na+ transport probably does not require glucose. Both insulin- and aldosterone-induced Na+ transport are directly proportional to serosal (but not mucosal) K+ concentration over the physiologic range (2.0-7.0 meq/liter). However, cycloheximide abolishes aldosterone- but not insulin-induced Na+ transport. In addition, insulin stimulates Na+ transport after a maximal response to aldosterone, and aldosterone stimulates Na+ transport after a maximal response to insulin. Thus, although they have several similar characteristics, insulin and aldosterone have at least partially independent mechanisms of action on Na+ transport in the toad urinary bladder.

Aldosterone↗
PubMed1983

Neurotransmission in activation of the contractile response in the human urinary bladder.

The endogenous contracting transmitter at the neuromuscular junction in strips from human urinary bladder has been investigated using field stimulation and selective antagonists. Atropine in low concentrations was found to inhibit bladder contractions whereas higher concentrations of the drug sometimes had the opposite effects. Indomethacin inhibited, phentolamine enhanced and methysergide had no dose-dependent effect on the field stimulation response. It is proposed that acetylcholine is one of the transmitter substances responsible for the contraction of the human detrusor. Species differences which could be responsible for the alleged atropine-resistance of the bladder are discussed. It is concluded that anticholinergic drugs should be of therapeutic value for treatment of muscular hyperactivity in the human urinary bladder.

Acetylcholine↗
PubMedDate not supplied

Urinary bladder tumors in dogs from 4,4'-methylene-bis (2-chloroaniline) (MOCA).

Six female beagle dogs were given a daily dose of 100 mg MOCA, by capsule, 3 days per week for the first 6 weeks and then 5 days per week continuously for periods up to 9.0 years. The dose varied from 8 to 15 mg/kg body weight/day among the dogs. Six female beagle dogs were kept as untreated controls. The test was terminated after 9.0 years of treatment. The average plasma glutamic-pyruvic transaminase activity of the dogs fed MOCA was higher than that of the controls during the first and last two years on test. During the eighth and ninth years the urine sediment from MOCA dogs contained excessive numbers of erythrocytes, leukocytes, and epithelial cells. Some epithelial cells contained abnormalities that suggested neoplasia in the genitourinary tract. One MOCA dog, sacrificed after 8.3 years on test was found to have a papillary transitional cell carcinoma of the urinary bladder. Of four MOCA dogs sacrificed after 9.0 years on test, three were found to have papillary transitional cell carcinomas of the urinary bladder and one had a combined transitional cell carcinoma and adenocarcinoma of the urethra. The urethral tumor had metastasized to the liver, but the papillary transitional cell carcinomas found in the other four dogs did not invade the muscle layers of the bladder wall and did not metastasize. Since no urinary bladder tumors were found in the six control dogs, MOCA was considered to be carcinogenic for the urinary bladder of dogs under the conditions employed (p less than 0.025, Fisher's Exact Test, one tail). Three of five MOCA dogs contained hyperplastic nodules in the liver with no such nodules in six control dogs (p greater than 0.05, Fisher's Exact Test, one tail). This was considered to be suggestive of an effect of MOCA treatment.

Animals↗