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PubMed1989

Distribution and density of neuropeptide Y-immunoreactive nerve fibres and cells in the horse urinary bladder.

The distribution and density of neuropeptide Y (NPY)-immunoreactive nerve fibres and cells were determined in the urinary bladder of the horse by using the peroxidase-antiperoxidase (PAP) immunohistochemical method. Numerous undulating NPY-immunoreactive nerve fibres were found throughout the vesical wall, sometimes forming nerve bundles which ramified repeatedly as they coursed through the connective tissue septa to give rise to smaller bundles or single fibres which projected into the muscle fascicles forming muscular nerve plexuses, mainly in the bladder base. In the submucosa of this region, NPY-immunoreactive fibres formed a rather dense subepithelial plexus. Numerous NPY-immunoreactive nerve fibres supplied blood vessels and were widely distributed on the vascular adventitia constituting rich perivascular nerve plexuses. In addition, intramural ganglia containing NPY-immunoreactive nerve cell bodies and fibres were identified at the uretero-vesical junction. These results suggest that the equine urinary bladder possesses a rich NPY-peptidergic innervation which shows regional variations in the density of the muscular and subepithelial plexuses, the bladder base being the most richly innervated region. At least some of these NPY-immunoreactive nerve fibres have an intrinsic origin in ganglion cells within the vesical wall.

Animals↗

PubMed1992

Inhibition of two-step urinary bladder carcinogenesis by the somatostatin analogue RC-160.

Fisher 344 female rats were exposed for 4 weeks to the initiator carcinogen N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) 0.05% in the drinking water and thereafter to the promoter carcinogen mitomycin C (0.08 mg per animal per week) intravesically for 12 weeks. High incidence of urinary bladder transitional cell cancers was observed (17 in situ and 17 invasive carcinomas among 40 rats). When the somatostatin analogue RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2) was administered s.c. at the dose of 50 micrograms per animal per day during 6-week period of promotion with mitomycin C, the incidence of urinary bladder cancer was dramatically reduced. Only 1 in situ carcinoma was observed among 20 rats and only preblastomatous lesions (dysplasias and papillomas) occurred. This effect could indicate that RC-160 interferes with the process of promotion by induction of enhanced apoptosis (programmed cell death) of the dysplastic urothelial cells. RC-160 could be tried therapeutically for the hormonal prevention of malignant transformation of preneoplastic lesions in the urinary bladder.

Amino Acid Sequence↗

PubMed1990

[Primary paraganglioma of the urinary bladder: a report of two cases].

We report two cases of primary paraganglioma of the urinary bladder. Case 1. A 61-year-old man was hospitalized with the chief complaints of gross hematuria, dysuria and headache. The patient had a history of hypertension. Cystoscopy disclosed a nonpapillary, sessile tumor in the retrotrigonum of the bladder. An attack of paroxysmal hypertension was induced by bimanual palpation of the tumor, and paraganglioma was suspected. Partial cystectomy with staging pelvic lymphadenectomy was performed. Case 2. A 65-year-old man was hospitalized with the chief complaints of gross hematuria and urinary retention. The patient had no history of hypertension. Cystoscopy disclosed a nonpapillary tumor in the right lateral wall of the bladder. Transurethral resection was performed with no cardiovascular complication. Prostatic needle biopsy showed the histological evidence of prostatic adenocarcinoma. Radical retropubic prostatectomy with limited lymphadenectomy was performed. There was no histological evidence of lymph node involvement of paraganglioma or adenocarcinoma. The histological and biochemical examinations revealed a chromaffin positive, functioning and non-malignant tumor in Case 1, and a chromaffin negative, non-functioning and non-malignant tumor in Case 2. In total, 29 cases of primary paraganglioma of the urinary bladder have been so far reported in Japan. The tumor recurrence, multiple or metastases were recorded in 8 of 29 cases (27.6%), mainly in regional lymph node metastases. We recommend lymphadenectomy at the initial operation, irrespective of pathological finding of the primary paraganglioma of the urinary bladder.

Aged↗

PubMed2005

Decreased phosphatase activity, increased Ca2+ sensitivity, and myosin light chain phosphorylation in urinary bladder smooth muscle of newborn mice.

Developmental changes in the regulation of smooth muscle contraction were examined in urinary bladder smooth muscle from mice. Maximal active stress was lower in newborn tissue compared with adult, and it was correlated with a lower content of actin and myosin. Sensitivity to extracellular Ca2+ during high-K+ contraction, was higher in newborn compared with 3-wk-old and adult bladder strips. Concentrations at half maximal tension (EC50) were 0.57 +/- 0.01, 1.14 +/- 0.12, and 1.31 +/- 0.08 mM. Force of the newborn tissue was inhibited by approximately 45% by the nonmuscle myosin inhibitor Blebbistatin, whereas adult tissue was not affected. The calcium sensitivity in newborn tissue was not affected by Blebbistatin, suggesting that nonmuscle myosin is not a primary cause for increased calcium sensitivity. The relation between intracellular [Ca2+] and force was shifted toward lower [Ca2+] in the newborn bladders. This increased Ca2+ sensitivity was also found in permeabilized muscles (EC50: 6.10 +/- 0.07, 5.77 +/- 0.08, and 5.55 +/- 0.02 pCa units, in newborn, 3-wk-old, and adult tissues). It was associated with an increased myosin light chain phosphorylation and a decreased rate of dephosphorylation. No difference was observed in the myosin light chain phosphorylation rate, whereas the rate of myosin light chain phosphatase-induced relaxation was about twofold slower in the newborn tissue. The decreased rate was associated with a lower expression of the phosphatase regulatory subunit MYPT-1 in newborn tissue. The results show that myosin light chain phosphatase activity can be developmentally regulated in mammalian urinary bladders. The resultant alterations in Ca2+ sensitivity may be of importance for the nervous and myogenic control of the newborn bladders.

Animals↗

PubMed2006

Cytokeratin-20 and seminal vesicle secretory protein VI as possible marker proteins in urinary bladder preneoplastic lesions induced by N-butyl-N-(4-hydroxybutyl) nitrosamine.

BACKGROUND: A simple and non-invasive methods for the diagnosis of transitional cell carcinoma of the bladder are needed for the prevention of invasive tumor. A proteomic technology has recently been developed to facilitate protein profiling of biological mixtures. We tried to detect the marker proteins by proteomic approach during the initiation stages on N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder carcinogenesis in rats. METHODS: Ten rats in group A were given 0.05% BBN in drinking water for 12 weeks. Other 10 rats in group B with 10 rats were designated as a control group and were not given BBN. Whole urinary bladders of all rats were excised at 12 weeks from the beginning of the experiment. Conventional proteomics was performed with high resolution 2-dimension gel electrophoresis followed by computational image analysis and protein identification using mass spectrometry. RESULTS: A comparison of urinary bladder hyperplasia tissue with control tissue showed that five proteins; actin gamma2 propeptide, cytokeratin-20 (CK-20), proapolipoprotein, alpha2 actin (alpha-cardiac actin) and heat shock 27 kDa protein-1 were over-expressed in hyperplastic tissues. Three proteins; transcription factor myocardin, seminal vesicle secretory protein VI (SVS-VI) precursor and hypothetical protein RMT-7 were under-expressed in hyperplastic tissues. CONCLUSION: In our animal mode, BBN-induced urinary bladder mucosal hyperplasia resulted in an increase in the expression of five proteins and a decrease in the expression of three proteins. Of these, CK-20 and SVS-VI seem to be of particular interest. However other method such as Western blotting seems to be needed for confirmation of these proteins and more information on human bladder tissue is needed for clinical application.

Animals↗

PubMed2001

Investigation of human papillomavirus in transitional cell carcinomas of the urinary bladder in South Africa.

AIM: To investigate the prevalence of human papillomavirus in transitional cell carcinoma of the urinary bladder in South Africa. METHODS: Ninety-one archival samples of bladder transitional cell carcinoma were subjected to polymerase chain reaction (PCR) and non-isotopic in situ hybridisation (NISH) for the detection of human papillomavirus 6, 11, 16, 18, 31, and 33 genotypes. RESULTS: HPV was detected in only one case with PCR. HPV was not detected in any of the cases subjected to the NISH system. CONCLUSION: This study shows that although HPV has been shown to be associated with uterine cervical and esophageal squamous cell carcinomas in South Africa, this virus is not present in the transitional cell carcinoma of the urinary bladder in this geographical location. It is suggested that other factors, including nitrosamine exposure, p53 mutation, and additional unknown chromosomal events, may play a role in the carcinogenesis of this neoplasm in the bladder.

Beta-Globulins↗

PubMed1996

[Cavernous hemangioma of urinary bladder: a case report and review of the literature].

We report a case of cavernous hemangioma of the urinary bladder treated with transurethral resection (TUR). A 58-year-old woman was admitted to our department with the chief complaint of macroscopic hematuria. Cystoscopy revealed a red sessile tumor 2 cm in diameter, at the internal urethral orifice. The tumor had a mostly low signal intensity, partly high signal intensity, on T1-weighted, coronal magnetic resonance (MR) images. Computed tomography and T2-weighted MR images did not delineate the tumor. TUR was performed, and the specimen was pathologically diagnosed as cavernous hemangioma of the urinary bladder. A brief description of the case is provided and the literature is reviewed.

Female↗

PubMed1994

Comparative biochemical characteristics of the cat and rabbit urinary bladder.

The cat and the rabbit are two of the most popular models for the study of lower urinary bladder function. The cat has been used extensively for in vivo studies of spinal and supra-spinal micturition reflexes. In contrast, the rabbit has been used extensively for the in vitro study of bladder function. Although the cat and rabbit bladders are approximately the same mass, the cat bladder can generate approximately 6 times the intravesical pressure than the rabbit bladder at the same volume (in vitro response to field stimulation). In order to determine if the increased pressure generation is related to increased cellular energetics, we compared the intracellular concentrations of ATP and creatine phosphate (CP), and the enzyme activities of three enzymes which have important functions in cellular energetics: creatine kinase, citrate synthase, and malic dehydrogenase between the cat and rabbit urinary bladder. The results can be summarized as follows: (1) The bladder weight of the cat and rabbit are similar. (2) The isolated cat bladder can generate approximately 6 times the intravesical pressure of the isolated rabbit bladder. (3) The ATP and CP concentrations of the rabbit are significantly greater than the concentrations in the cat bladder. (4) The hydroxyproline concentration is significantly greater in the cat than the rabbit. (5) The maximum activities of creatine kinase, citrate synthase, and malic dehydrogenase are significantly lower in the cat than the rabbit. In general, it is clear that the ability of the cat to generate high intravesical pressures is not correlated with increased tissue high energy phosphate concentrations, or high enzymatic activities of three specific cytosolic or mitochondrial enzymes.

Adenosine Triphosphate↗

PubMed1993

[A case of asynchronous renal cell carcinoma and urothelial cancer of the urinary bladder and left ureter].

A 49-year-old male with left renal cell carcinoma and urothelial cancer (bladder and residual left ureter), which asynchronously occurred, was reported. He had received radical nephrectomy due to renal cell carcinoma 12 years earlier. He was followed up by his local physician for 7 years postoperatively, during which time no metastatic lesion was detected. However, he presented with macroscopic hematuria on January 7, 1992, and a diagnosis of urinary bladder cancer was made at our hospital. Computerized tomography demonstrated a non-papillary, broad-based tumor on the left wall of the urinary bladder, which histologically was transitional cell carcinoma (grade 3). Radical cystectomy, ureterectomy of the left residual ureter and ileal conduit were performed. Histological examinations showed that the urinary bladder tumor was transitional cell carcinoma, grade 3, pT-3b, and CIS (transitional cell carcinoma, grade 3) was found in the residual left ureter. Chemotherapy containing cis-platinum was performed as an adjuvant therapy, but multiple lung metastatic lesions appeared 2 months postoperatively, the histology of which was transitional cell carcinoma, suggesting metastasis from the urothelial cancer. Chemotherapy was ineffective, and he died of the disease 9 months after the operation. If this patient had been under long-term follow-up, the urothelial cancer may have been resected completely by transurethral resection. Our report indicated the importance of examination of the urinary tract in patients with such cancers, as well as the necessity of long-term follow-up.

Carcinoma, Renal Cell↗

PubMed1995

Influence of strip size and location on contractile responses of rat urinary bladder body strips.

1. We investigated the influence of strip length and dorsal or ventral location of rat urinary bladder strips on contractile responsiveness. 2. No differences occurred in the contractile responses of 0.5, 1.0 and 2.0 cm strips to field stimulation, carbachol, ATP, substance P or to KCl when the data were expressed as either absolute tension or as tension per cross-sectional area. However, correction for strip mass resulted in significant decreases in the contractile responses of the 2.0-cm strips compared with the 0.5-cm strips. 3. No differences occurred in length-tension curves for ventral and dorsal bladder strips, even though the strips from the dorsal surface appeared thinner than those from the ventral surface. 4. Strips from the ventral surface exhibited more variability in response to field stimulation and were less sensitive to atropine pre-treatment than were those from the dorsal surface. They were also less sensitive to the contractile effects of carbachol than dorsal strips. Dorsal and ventral strips were equally responsive to ATP, substance P and KCl. 5. Our data indicate that the contractile responsiveness of rat urinary bladder strips is independent of strip length. Although there are some differences between the cholinergic responsiveness of strips from the ventral and dorsal surfaces of the bladder, the differences are so small that for most studies they will probably have no influence on data interpretation.

Adenosine Triphosphate↗

PubMed1990

Urothelial damage and tumor initiation by urinary metabolites of sodium o-phenylphenate in the urinary bladder of female rats.

Intravesical instillation of 2-phenyl-1,4-benzoquinone (PBQ), a metabolite of sodium o-phenylphenate (Na-OPP), at a concentration of 0.1% in saline caused acute epithelial injury, prolonged inflammation and epithelial hyperplasia in female F344 rats. Ten such instillations of PBQ within 5 weeks resulted in the development of preneoplastic lesions of the urinary bladder epithelium when followed by 5% sodium saccharin feeding for 31 weeks. Since neither urothelial damage nor tumor-initiating activity was observed with either Na-OPP itself or another metabolite, phenylhydroquinone, PBQ may play an essential role in Na-OPP urinary bladder carcinogenesis.

Administration, Intravesical↗

PubMed1982

Tumours in Iceland. 6. Tumours of the urinary bladder, ureter and urethra. A histological classification and some epidemiological and environmental factors.

All primary tumours from the urinary bladder, ureter and urethra submitted for a histological diagnosis in Iceland during the 20 years, 1955-1974, and available for review, were typed histologically according to the World Health Organization Classification published in 1973. The series included 237 tumours, and of these 94.5 per cent were from the bladder. Transitional cell carcinomas constituted the largest group, or 120 in males and 77 in females. For transitional cell carcinomas there was a good correlation between growth patterns, grades and pathological stages. Most of the papillary carcinomas were of grades 1 and 2 and all the purely infiltrating carcinomas were of grade 3. The papillary carcinomas were predominantly superficial and the purely infiltrating were deeply invasive and the degree of cellular anaplasia increased with the depth of invasion from the lamina propria to perivesical tissue and other organs. The incidence of transitional cell carcinoma of the urinary bladder is rising in Icelanders and the incidence in females is the highest reported among European nations. Industrial chemical carcinogens are an unlikely cause of bladder carcinoma in Icelanders but cigarette smoking, and a high consumption of coffee and salted food may play an important role.

Carcinogens, Environmental↗

PubMed2002

Prognostic significance of tumour angiogenesis in schistosoma-associated adenocarcinoma of the urinary bladder.

OBJECTIVE: To report on tumour angiogenesis and its relationship with morphological variables and prognosis in adenocarcinoma of the urinary bladder associated with schistosomiasis. PATIENTS AND METHODS: Fifty-five vesical adenocarcinomas were evaluated from 30 men and 25 women (mean age 47.2 years, sd 8.7, range 30-65) who were followed up after radical cystectomy and urinary diversion for a mean (sd, range) of 61 (43.5, 2.7-159.5) months. Vessels were stained immunohistochemically using an antibody to the platelet endothelial cell-adhesion molecule CD31. Microvessels were counted in active areas of angiogenesis within the tumours (at x250) and the microvessel density (MVD) quantified using the mean of three counts. Treatment failure was defined as death from cancer or the development of local recurrence or distant metastasis. Kaplan-Meier survival curves and Cox's proportional hazard model were used to assess survival. RESULTS: The overall 5- and 10-year survival rates were 57% and 51%, respectively. The presence of lymph node metastasis and high mean vascular density (> 26) were significantly associated with a poor prognosis. The 5-year survival for patients with negative lymph nodes was 66% while no patients with positive nodes survived for 5 years (P < 0.001); the survival was 72% for patients with a low MVD and 33% for those with a high MVD (P = 0.0016). From individual results plotted against vascularity in lymph node-negative patients, there was a significantly better outcome for those with a low MVD (< or = 26; P = 0.0099); this significance was maintained on multivariate analysis. However, there was no significant relationship between angiogenesis and the different clinicopathological factors apart from the grade (P = 0.03); tumour stage, grade and DNA profile had no significant effect on survival in these patients. CONCLUSIONS: These findings suggest that assessing angiogenesis using the MVD provides an independent predictor of survival in patients with adenocarcinoma of the urinary bladder.

Adenocarcinoma↗

PubMed1989

[Arg8]vasopressin-induced contractions of rabbit urinary bladder smooth muscle.

The effects of a number of neurohypophyseal hormones and analogues on the contractility of rabbit urinary bladder smooth muscle in vitro were examined. The order of potency was [Arg8]vasopressin = [Lys8]vasotocin greater than [Lys8]vasopressin greater than [Arg8]vasotocin much greater than [deamino1,D-Arg8]vasopressin greater than oxytocin much greater than pressinoic acid. The maximum tension induced by [Arg8]vasopressin was 4.4 N . cm-2 and the pD2 was 8.7. The effects of [Arg8]vasopressin were competitively antagonized by [(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)1,(O-methyl)Tyr2,Arg8]vasopressin and by [deaminopenicillamine1,Val4,D-Arg8]vasopressin with pA2s of 8.4 and 6.6, respectively. It was concluded that rabbit urinary bladder smooth muscle contains receptors for the neurohypophyseal hormones which have recognition properties similar to V1-vasopressin receptors.

Animals↗

PubMed1989

Cystometric evaluation of early and late irradiation damage to the mouse urinary bladder.

The present study reports a simple, non-invasive, in vivo method for detecting early and late radiation damage to the mouse urinary bladder using transurethral bladder filling. The study also describes a useful experimental model for irradiation of mouse urinary bladder without any concomitant irradiation of the rectum and bony structures and maximal shielding of the small intestine. Within 30 days after single fraction bladder irradiation at 5-30 Gy, repeated cystometric investigations reveal a change in the reservoir function of the bladder illustrated by a considerable dose-dependent decrease in the compliance of the bladder wall. The changes in the reservoir function is reversible hence the bladder function is restored after another month. At various time intervals after the irradiation, however, the late radiation damage appears, the time of manifestation being dose-dependent. This final change is irreversible and consistent with the clinically known contracted bladder.

Animals↗

PubMed1989

Phase II study of carboplatin in locally advanced and metastatic transitional cell carcinoma of the urinary bladder.

Twenty-five previously untreated patients with measurable locally advanced and/or metastatic transitional cell carcinoma of the urinary bladder were included in a phase II study with carboplatin. Bolus injections were administered in 2 courses every 4 weeks at an initial dose of 400 to 450 mg/m2 with the option of increasing the dose to 450 to 500 mg/m2 in individual patients during the second cycle, depending on haematological toxicity. Two patients had a complete response (CR), 13 showed no change (NC) and 9 had progression of disease (PD), including 4 early progressions. There was no delay in treatment because of myelosuppression. Thrombocytopenia led to a reduction in drug dosage. No reduction in renal function was observed. Increased dosage did not increase the response rate. This study indicated the low effectiveness of single agent carboplatin in transitional cell carcinoma of the urinary bladder.

Adult↗

PubMed1990

Intravesical mitomycin C for carcinoma in situ of the urinary bladder.

Mitomycin C was given intravesically over periods of 2-32 months to 34 patients with carcinoma in situ of the urinary bladder. Initial complete response was obtained in 17 patients, 14 of whom remained without evidence of disease during follow-up averaging 28 months from cessation of mitomycin therapy. In three responding patients malignant cells reappeared in the urine during follow-up, although no recurrence of carcinoma could be proven in bladder biopsy specimens. In eight of the 17 non-responders, muscle invasion and/or metastatic disease developed during or after mitomycin treatment. The prostatic urethra was involved in five cases. Chemotherapy had to be discontinued because of chemical cystitis in three cases. Mitomycin C appears to be effective for intravesical treatment of carcinoma in situ of the urinary bladder. Close surveillance of these patients is mandatory, however, and must include monitoring not only of the bladder, but also of the prostatic urethra and the upper urinary tract.

Administration, Intravesical↗

PubMed2006

Promoter hypermethylation of the 14-3-3 sigma, SYK and CAGE-1 genes is related to the various phenotypes of urinary bladder carcinomas and associated with progression of transitional cell carcinomas.

To explore the significance of epigenetic mechanisms in urinary bladder carcinogenesis mediated by methylation of cytosine in CpG dinucleotides at 5' promoter regions, we analysed the methylation status of a broad panel of different genes in transitional cell carcinomas (TCC) and nonurothelial cancers, among which the 14-3-3 sigma, SYK and CAGE-1 genes were recognised as promising target genes. Using methylation-specific PCR, the rate of DNA hypermethylation proved to be related to the various histopathological cancer subtypes. The higher frequency of promoter methylation of the 14-3-3 sigma (57.1%) and SYK (64.3%) genes in high-grade, high-stage TCC in association with a reduced or even lacking immunohistochemical protein expression than in low-grade, low-stage TCC (28.6% and 42.9%, respectively), indicates that aberrant methylation of these genes plays an essential role in the progression of TCC. The importance of DNA hypermethylation in the conversion of TCC from a low to a high malignant potential was strongly supported by the finding that, unlike superficial low-grade TCC, advanced muscle invasive TCC showed a concurrent promoter methylation of the 14-3-3 sigma, SYK and CAGE-1 genes. Squamous cell carcinomas revealed a peak incidence of hypermethylation of the 14-3-3 sigma gene (80%), and conversely, the lowest methylation frequency of the SYK gene (13.3%). Undifferentiated small cell carcinomas disclosed a promoter methylation of the 14-3-3 sigma, SYK and CAGE-1 genes in only a quarter each for the cases. Although a correlation between the methylation status and gene activity in squamous cell and undifferentiated small cell carcinomas was not observed, the underexpression of the SYK protein products in both cancer types and additionally of the 14-3-3 sigma protein in small cell carcinomas appeared to be related to the aggressive clinical behaviour of both these nonurothelial bladder carcinomas. The relevance of the high frequency of DNA hypermethylation of the CAGE-1 antigen in TCC and squamous cell carcinomas merits further study, particularly in relation to anticancer immunotherapy. The methylation status of the PTEN, COX-2, RUNX-3 and HIC-1 genes was found to be unaltered. In conclusion, the different patterns of aberrant methylation of the 14-3-3 sigma, SYK and CAGE-1 genes in the various histopathological cancer types of the urinary bladder point to a role in tumor cell differentiation, resulting in the phenotypical conversion of TCC into nonurothelial carcinomas and in the progression of TCC to a more malignant potential.

14-3-3 Proteins↗

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