Showing papers on "Urinary bladder published in 2000"

Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice.

Abstract: Extracellular ATP is implicated in numerous sensory processes ranging from the response to pain to the regulation of motility in visceral organs. The ATP receptor P2X3 is selectively expressed on small diameter sensory neurons, supporting this hypothesis. Here we show that mice deficient in P2X3 lose the rapidly desensitizing ATP-induced currents in dorsal root ganglion neurons. P2X3 deficiency also causes a reduction in the sustained ATP-induced currents in nodose ganglion neurons. P2X3-null mice have reduced pain-related behaviour in response to injection of ATP and formalin. Significantly, P2X3-null mice exhibit a marked urinary bladder hyporeflexia, characterized by decreased voiding frequency and increased bladder capacity, but normal bladder pressures. Immunohistochemical studies localize P2X3 to nerve fibres innervating the urinary bladder of wild-type mice, and show that loss of P2X3 does not alter sensory neuron innervation density. Thus, P2X3 is critical for peripheral pain responses and afferent pathways controlling urinary bladder volume reflexes. Antagonists to P2X3 may therefore have therapeutic potential in the treatment of disorders of urine storage and voiding such as overactive bladder.

Cigarette smoking and bladder cancer in men: a pooled analysis of 11 case-control studies.

Abstract: The primary risk factor for bladder cancer is cigarette smoking. Using a combined analysis of 11 case-control studies, we have accurately measured the relationship between cigarette smoking and bladder cancer in men. Available smoking information on 2,600 male bladder cancer cases and 5,524 male controls included duration of smoking habit, number of cigarettes smoked per day and time since cessation of smoking habit for ex-smokers. There was a linear increasing risk of bladder cancer with increasing duration of smoking, ranging from an odds ratio (OR) of 1.96 after 20 years of smoking (95% confidence interval [CI] 1.48–2.61) to 5.57 after 60 years (CI 4.18–7.44). A dose relationship was observed between number of cigarettes smoked per day and bladder cancer up to a threshold limit of 15–20 cigarettes per day, OR = 4.50 (CI 3.81–5.33), after which no increased risk was observed. An immediate decrease in risk of bladder cancer was observed for those who gave up smoking. This decrease was over 30% after 1–4 years, OR = 0.65 (0.53–0.79), and was over 60% after 25 years of cessation, OR = 0.37 (0.30–0.45). However, even after 25 years, the decrease in risk did not reach the level of the never-smokers, OR = 0.20. (0.17–0.24). The proportion of bladder cancer cases attributable to ever-smoking was 0.66 (0.61–0.70) for all men and 0.73 (0.66–0.79) for men younger than 60. These estimates are higher than previously calculated. Int. J. Cancer 86:289–294, 2000. © 2000 Wiley-Liss, Inc.

Everything you wanted to know about the bladder epithelium but were afraid to ask

Abstract: The mammalian urinary bladder epithelium (urothelium) performs the important function of storing urine for extended periods, while maintaining the urine composition similar to that delivered by the kidneys. The urothelium possesses four properties to perform this function. First, it offers a minimum epithelial surface area-to-urine volume; this reduces the surface area for passive movement of substances between lumen and blood. Second, the passive permeability of the apical membrane and tight junctions is very low to electrolytes and nonelectrolytes. Third, the urothelium has a hormonally regulated sodium absorptive system; thus passive movement of sodium from blood to urine is countered by active sodium reabsorption. Last, the permeability properties of the apical membrane and tight junctions of the urothelium are not altered by most substances found in the urine or blood. The importance of the barrier function of the urothelium is illustrated by infectious cystitis. The loss of the barrier function results in the movement of urinary constituents into the lamina propria and underlying muscle layers, resulting in suprapubic and lower back pain and frequent, urgent, and painful voiding.

Celecoxib Inhibits N-Butyl-N-(4-hydroxybutyl)-nitrosamine-induced Urinary Bladder Cancers in Male B6D2F1 Mice and Female Fischer-344 Rats

Abstract: Epidemiological studies have shown that nonsteroidal anti-inflammatory drugs (NSAIDs) may have a role in the prevention of human cancers. A number of preclinical studies have also suggested that inhibition of cyclooxygenase (COX) with NSAIDs has an anticancer effect in animal models of colon, urinary bladder, skin, and breast. In these studies, we evaluated the COX-2 inhibitor celecoxib in two rodent models of urinary bladder cancer. Male B6D2F1 mice treated with N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) developed transitional and squamous cell urinary bladder cancers, many of which grew rapidly and caused substantial morbidity that required sacrifice of the mice. Groups of mice received various daily doses of celecoxib in the diet (1250, 500, or 200 mg/kg of diet) beginning 7 days before the initiation of 12 weekly doses of OH-BBN. Mice were checked weekly for the presence of palpable urinary bladder masses. The study was terminated at 8 months following the initial treatment with OH-BBN. The percentage of mice with large palpable bladder lesions, which necessitated sacrifice of the mice, was 40% in the OH-BBN control group. In contrast, only 10% of all celecoxib-treated mice required sacrifice before the scheduled termination of the experiment, implying that all three doses of celecoxib inhibited the formation of large palpable lesions. Celecoxib did not significantly alter the incidence of preneoplastic bladder lesions, but did dose-dependently decrease the total number of urinary bladder cancers/mouse, palpable plus microscopic, by 77, 57, and 43% at dosages of 1250, 500, and 200 mg of celecoxib/kg of diet, respectively. In the second model, female Fischer-344 rats were administered OH-BBN twice/week for a period of 8 weeks. After 8 months, all rats developed preneoplastic lesions, whereas roughly 60% of the rats developed relatively small urinary bladder cancers. Rats were treated continually with celecoxib in the diet (500 or 1000 mg/kg of diet) beginning either 1 week prior to the initial OH-BBN treatment or beginning 1 week following the last OH-BBN treatment. Neither celecoxib treatment regimen significantly altered the number of preneoplastic lesions. Whereas celecoxib treatment initiated prior to OH-BBN administration decreased cancer incidence roughly 65%, celecoxib treatment initiated beginning 1 week after the last dose of OH-BBN profoundly decreased cancer incidence (>95%). Celecoxib did not alter the body weights of the mice or rats, or cause other signs of toxicity at any of the doses studied. Taken together these results demonstrate that: (a) celecoxib effectively inhibits tumor growth and enhances survival in the mouse model of urinary bladder cancer; and (b) celecoxib profoundly inhibits development of urinary bladder cancers in the rat model even when administered following the last dose of OH-BBN. Clinical trials will be necessary to determine whether COX-2 inhibitors will provide a clinical benefit in human bladder cancer.

Urothelium-derived inhibitory factor(s) influences on detrusor muscle contractility in vitro.

Abstract: The function of the bladder urothelium in modulating contractile responses of the underlying detrusor smooth muscle to muscarinic stimulation has been examined in the pig bladder. Saturation curves for [3H]-QNB binding demonstrated a greater muscarinic receptor density in the urothelium than in the detrusor smooth muscle. The presence of an intact urothelium on isolated bladder strips inhibited contractions induced by carbachol but not KCl. Contractions of a urothelium-denuded muscle strip were inhibited in the presence of a second bladder strip with an intact urothelium, but not if the second strip was denuded. The urothelium-induced inhibition of contractions was not prevented in the presence of L-NOARG, methylene blue, indomethacin, propranolol, suramin, TEA or apamin. The data suggest the presence of a diffusable, urothelium-derived inhibitory factor, which could not be identified but appears to be neither nitric oxide, a cyclo-oxygenase product, a catecholamine, adenosine, GABA nor an EDHF sensitive to apamin.

Efficacy and Safety of Bacille Calmette-Guérin Immunotherapy in Superficial Bladder Cancer

Abstract: In the United States, bladder cancer is the fourth most common human malignancy. In the past decade, the incidence of bladder cancer has increased by 36%. However, mortality has declined by 8%. Intravesical chemotherapy was considered to be partially responsible for this improvement in survival, but a recent review of clinical studies shows no reduction in disease progression with intravesical chemotherapy. Fortunately, the results of immunotherapy with bacille Calmette-Guerin (BCG) are quite different, and it is expected that patients treated with optimal BCG treatment regimens will have a long-term reduction in tumor recurrence, tumor progression, and cancer mortality.

Naturally-occurring canine transitional cell carcinoma of the urinary bladder A relevant model of human invasive bladder cancer.

Abstract: Invasive bladder cancer results in over 10,000 deaths yearly in the United States alone. More effective therapy for invasive bladder cancer is clearly needed. As new cellular and molecular targets for therapy are identified, relevant animal models are needed to test new therapeutic strategies aimed at these targets prior to human clinical trials. The purpose of this review is to characterize spontaneous invasive transitional cell carcinoma of the urinary bladder (TCC) in dogs, to summarize the similarities and differences between canine and human invasive TCC, and to describe how canine TCC could serve as a relevant model of human invasive bladder cancer. Information was summarized from 102 dogs with TCC evaluated and treated at the Purdue University Veterinary Teaching Hospital, from a review of the Veterinary Medical Data Base, and from reports in the literature. Canine TCC was found to be very similar to human invasive bladder cancer in histopathologic characteristics, molecular features, biological behavior including metastasis, response to medical therapy, and prognosis. Differences between canine and human TCC were few, but included gender predilection with a male:female ratio of 2.8:1 in humans versus a male:female ratio of 0.5:1 in dogs. The location of the TCC within the bladder also differed: Most canine TCC was trigonal in location, whereas more than 50% of human TCC was in the lateral and posterior walls of the bladder. Considering the great similarity between invasive bladder cancer in humans and dogs, spontaneous canine TCC can be considered a relevant animal model of human invasive bladder cancer.

Frequent alteration of p63 expression in human primary bladder carcinomas.

Abstract: p63, a recently identified member of the p53 gene family, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. To explore the penetrance of p63 in bladder carcinogenesis, we performed expression and mutation analyses of two major isotypes, TAp63 and deltaNp63, in 63 bladder specimens. In 12 normal tissues, TAp63 was expressed at an easily detectable level whereas deltaNp63 was absent or extremely low. While none of 47 carcinomas showed allelic deletion of the gene, marked reduction of TAp63 and abnormal overexpression of deltaNp63 were found in 25 (53.2%) and 30 (63.8%) carcinomas, respectively. Tumor-specific alteration of TAp63 and deltaNp63 expression was identified in two and three of six matched sets, respectively. In addition, reduced expression of TAp63 showed a correlation with tumor stage and grade. Abnormal expression of TAp63 or deltaNp63 isoform was also observed in three of four cell lines, and treatment with 5-Aza-2'-deoxycytidine led to up- or down-regulation of TAp63 and/or deltaNp63 expression, suggesting that the promoters of both isoforms might be affected by DNA methylation, but not in a reciprocal fashion. No sequence alteration of p63 was identified in 47 carcinomas whereas 17 (34.8%) of these showed p53 mutations, and no association between p63 expression and the mutational status of p53 or expression of p21Waf1, MDM2, and 14-3-3sigma was recognized. Our data suggest that altered expression of p63 is a frequent event in bladder carcinogenesis and might contribute to the progression of bladder tumors, possibly via the mechanism(s) distinct from the p53 pathway.

Treatment of neurogenic incontinence with botulinum toxin A.

Abstract: To the Editor: Neurogenic urinary incontinence is most often due to detrusor hyperreflexia, and it is usually treated by partially blocking the efferent parasympathetic innervation to the detrusor muscle of the bladder with anticholinergic drugs. These drugs have troublesome side effects, however, and may not restore continence. Botulinum toxin A selectively blocks the release of acetylcholine from nerve endings and accordingly blocks neural transmission. We hypothesized that injections of botulinum toxin A into the detrusor muscle of the bladder might ameliorate detrusor hyperreflexia in patients with neurogenic incontinence by impairing parasympathetic nervous transmission. During the past year, we treated 21 . . .

Cerebral activation during micturition in normal men.

Abstract: Specific cerebral lesions have shown the crucial role of the brain in the control of micturition. The precise identification of the anatomical cerebral structures involved in micturition can contribute to a better understanding of the control of micturition and the development of therapeutic models. Various neuropathological and animal studies have referred to the medulla oblongata, pons, limbic system, superior frontal lobe and premotor cortical regions as areas implicated in micturition control. The aim of this study was to investigate whether the activity of these areas during micturition can be confirmed by PET in normal men. The distribution of the regional cerebral blood flow after bolus injection of (15)O water was used as an indirect measure of cerebral activation. PET scans were performed during the following three conditions: (i) at rest with the bladder empty; (ii) during simulated micturition after instillation of isotonic saline into the urinary bladder; and (iii) the withholding of urine (saline). Normal micturition using this model was achieved in eight out of 12 right-handed normal subjects. The changes in bladder contraction, bladder pressure and intra-abdominal pressure were monitored on-line during the whole scanning session by a cystometry device. The images were analysed using statistical parametric mapping at a significance threshold of P 3.09) without correction for multiple comparisons, we found additional activation in the medial pontine tegmentum, mesencephalon, right thalamus, right middle frontal gyrus and left insula. When urine- withholding was compared with rest, the left insula showed a tendency to activate. We conclude from this study, in which urinary bladder contraction was verified cystometrically, that the onset and maintenance of micturition in normal men is associated with a vast network of cortical and subcortical regions, confirming observations from clinical and animal studies.

Non-steroidal anti-inflammatory drugs and bladder cancer prevention.

Abstract: Inclusion of phenacetin among ‘proven’ human carcinogens by the IARC in 1987, raised concerns about the carcinogenic potential of acetaminophen, its major metabolite Acetaminophen has been implicated as a possible causal agent in the development of cancer of the renal pelvis The bladder and renal pelvis, which derive from the same embryological structure, share the same transitional type of epithelium Past studies have been inconclusive on the possible relationship among these analgesics and bladder cancer but no large, highly detailed study of this association has been conducted A population-based case–control study conducted in Los Angeles, California, involved 1514 incident bladder cancer cases and an equal number of controls who were matched to the index cases by sex, date of birth (within 5 years) and race Detailed information on medication use and prior medical conditions was collected through in-person interviews Regular use of analgesics was not associated with an increased risk of bladder cancer in either men or women In fact, compared with non- or irregular users, regular analgesic users were at a decreased risk of bladder cancer overall (odds ratio (OR) = 081, 95% confidence interval (CI) = 068–096) However, there were clear differences in both the direction and strength of the associations between the different formulation classes of analgesics and bladder cancer risk Intake of phenacetin was positively related to bladder cancer risk in a dose-dependent manner while intake of its major metabolite in humans, acetaminophen, was unrelated to risk Intake of all classes of NSAIDs, except pyrazolon derivatives, were negatively associated with bladder cancer risk, with suggestive evidence that the protective effect varies in strength by subcategories of formulation Acetic acids seemed to exhibit the strongest protective effect, whereas aspirin/other salicylic acids and oxicam showed the weakest protection © 2000 Cancer Research Campaign

Secondary neoplasms of the bladder are histological mimics of nontransitional cell primary tumours: clinicopathological and histological features of 282 cases

Abstract: Aims The incidence, anatomical localization and histological appearances of secondary neoplasms of the urinary bladder are described, with emphasis on the points of distinction from primary tumours. Methods and results A retrospective study of cases at the Royal Hospitals Trust yielded a total of 282 secondary bladder neoplasms, representing 2.3% of all malignant bladder tumours in surgical specimens. The commonest primary sites were the colon (21% of secondary neoplasms), prostate (19%), rectum (12%) and cervix (11%). Most tumours from these sites reached the bladder by direct spread. The most common sites of origin of tumours metastatic to the bladder were stomach (4.3% of all secondary bladder neoplasms), skin (3.9%), lung (2.8%), and breast (2.5%). Secondary tumour deposits were almost always solitary (96.7%), and 54% were located in the bladder neck or trigone. Histologically, 54% of secondary tumours were adenocarcinomas. Immunohistochemical staining patterns with prostate-specific acid phosphatase, prostate-specific antigen, carcinoembryonic antigen, chromogranin and neurone-specific enolase were similar in primary vesical and urachal adenocarcinomas and secondary adenocarcinomas from the gastrointestinal tract. Conclusions The incidence of secondary bladder tumours is comparable to that of nontransitional cell primary tumours. Few secondary tumours have distinctive histological features, hence knowledge of the history and clinical investigations are particularly important in their diagnosis.