Background: Urinary incontinence (UI) is a common problem in adults, especially among the elderly. We examined the prevalence and risk factors of UI and potential factors hindering individuals from seeking treatment for UI among a community-dwelling population aged over 40 years. Methods: Data were collected by mailing a 23-item urinary incontinence questionnaire to a random sample of community-dwelling individuals aged 40-75 years (n = 3500) in seven towns of Shiga Prefecture, Japan. Collected data were then used to estimate the prevalence of UI and to provide information regarding subtypes of UI, knowledge and self-perception about UI. Results: The overall response rate was 52.5%. Prevalence of UI for male and female respondents were 10.5% and 53.7%, respectively. The incidence of urge incontinence increased as age increased in the male group. In women, stress incontinence was prevalent at all ages and the incidence of urge incontinence increased over 70 years of age. Urinary incontinence was more likely as activities of daily living limitations and cystitis increased. Women with a history of hysterectomy or diabetes mellitus and men who had stroke were at increased risk for UI. Of those who reported UI, only 3% had ever consulted doctors or other health care professionals concerning it, 25% recognized their condition as a disease and 38% considered it curable by appropriate treatments. In addition, 63% regarded UI as an unavoidable consequence of aging, 63% considered their condition was embarrassing and 54% were reluctant to seek treatment from a health professional. Conclusions: Although UI is common among community-dwelling individuals over 40 years of age, the majority of affected individuals remained untreated due to lack of knowledge and/or a negative perception of UI. Thus, community education on UI may be needed to increase the number of UI patients who receive treatment.
Background: New methods for detection of bladder cancer are needed because cystoscopy is both invasive and expensive and urine cytology has low sensitivity. We screened proteins as tumor markers for bladder cancer by proteomic analysis of cancerous and healthy tissues and investigated the diagnostic accuracy of one such marker in urine. Methods: Three specimens of bladder cancer and healthy urothelium, respectively, were used for proteome differential display using narrow-pH-range twodimensional electrophoresis. To evaluate the presence of calreticulin (CRT) as detected by Western blotting, we obtained 22 cancerous and 10 noncancerous surgical specimens from transurethral resection or radical cystectomy. To evaluate urinary CRT, we collected 70 and 181 urine samples from patients with and without bladder cancer, respectively. Anti-CRT COOH-terminus antibody was used to detect CRT in tissue and urine. Results: Proteomic analysis revealed increased CRT (55 kDa; pI 4.3) in cancer tissue. Quantitative Western blot analysis showed that CRT was increased in cancer tissue (P ؍ 0.0003). Urinary CRT had a sensitivity of 73% (95% confidence interval, 62-83%) at a specificity of 86% (80 -91%) for bladder cancer in the samples tested. Conclusions: Proteomic analysis is useful in searching for candidate proteins as biomarkers and led to the
The mainstay in the management of invasive bladder cancer continues to be radical cystectomy. With regard to improvement of quality of life, however, therapies that preserve the bladder are desirable. We investigated the use of intravesical PLK-1 small interfering RNA (siRNA) against bladder cancer. Patients with bladder cancers expressing high levels of PLK-1 have a poor prognosis compared with patients with low expression. Using siRNA/cationic liposomes, the expression of endogenous PLK-1 could be suppressed in bladder cancer cells in a time-and dose-dependent manner. As a consequence, PLK-1 functions were disrupted. Inhibition of bipolar spindle formation, accumulation of cyclin B1, reduced cell proliferation, and induction of apoptosis were observed. In order to determine the efficacy of the siRNA/liposomes in vivo, we established an orthotopic mouse model using a LUC-labeled bladder cancer cell line, UM-UC-3 LUC . PLK-1 siRNA was successfully transfected into the cells, reduced PLK-1 expression, and prevented the growth of bladder cancer in this mouse model. This is the first demonstration, to our knowledge, of inhibition of cancer growth in the murine bladder by intravesical siRNA/cationic liposomes. We believe intravesical siRNA instillation against bladder cancer will be useful as a therapeutic tool.
Using proteomic analysis, we previously identified calreticulin (CRT) as a potentially useful urinary marker for bladder cancer. Now, we have also identified γ γ γ γ-synuclein (SNCG) and a soluble isoform of catechol-o-methyltransferase (s-COMT) as novel candidates for tumor markers in bladder cancer, by means of proteomic analysis. In the process of establishing a superior tumor marker system, we investigated the diagnostic value of a combination assay of these three proteins. Voided urine samples were obtained from 112 bladder cancer and 230 control patients. Urinary CRT, SNCG, and s-COMT were measured as a combined marker by quantitative western blot analysis. Relative concentration of each protein was calculated and the diagnostic value of a concomitant examination of these markers was evaluated by receiver operator characteristic analysis. With the best diagnostic cutoff, the overall sensitivity of the combined markers was 76.8% (95% confidence interval, 69-81%) with a specificity of 77.4% (72-80%), while those of a single use of CRT were 71.4% and 77.8%, respectively. When evaluated in relation to tumor characteristics, such as grade, stage, size, and outcome of urinary cytology, the diagnostic capacity of the combined markers was equal to or better than that of CRT in all categories. Concomitant use of CRT, SNCG, and s-COMT had higher sensitivity for detection of bladder cancer than did single use of CRT. Our study suggests that use of this panel of markers will improve the diagnosis of bladder cancer and may allow the development of a protein microarray assay or multi-channel enzyme-linked immunosorbent assay. (Cancer Sci 2004; 95: 955-961) ladder cancer is a common urothelial cancer with an estimated 57,400 and 13,000 diagnosed cases per year in the United States and Japan, respectively. 1, 2) Approximately 70% of bladder cancers are superficial 3) and respond well to endoscopic transurethral resection. However, 50% to 70% of these patients experience tumor recurrence, and 10% to 15% of recurrent tumors progress to muscle invasive disease. 4) Because the propensity for local recurrence extends over the lifetime, patients with superficial bladder cancer must undergo life-long surveillance.Cystoscopy is the mainstay in diagnosing bladder cancer. However, this procedure is unsuitable for screening of large groups because of its invasiveness and expense. In addition, follow-up cystoscopy for bladder cancer patients treated endoscopically represents a considerable part of the workload of any urological unit. Therefore, new tests with high specificity and sensitivity that are easy to perform are needed for both screening and monitoring the response to treatment of bladder cancer. Voided urine cytology (VUC) has been used in both diagnosis and follow-up of superficial bladder cancer since its first description by Papanicolaou and Marshall in 1945, but it has poor sensitivity although high specificity, particularly in well-differentiated cancer.5) To date, several urine-based markers for bladder cancer have ...
Proteome analysis of bladder cancer with narrow-range pH 2-DE has identified a novel protein on chromosome 7 encoded by ORF 24 (C7orf24) as one of the highly expressed proteins in cancer cells. C7orf24 is currently registered in the protein database as a hypothetical protein with unknown function. The homologs of C7orf24 in other animals have also been registered as putative protein genes. Western blot analysis using a mAb against C7orf24 confirmed its higher expression in bladder cancer compared with normal tissue. Several other cancer cell lines were also found to express C7orf24. However, the introduction of C7orf24 into Rat-1 or NIH3T3 cells did not cause malignant transformation. A stable transfectant of NIH3T3 cells with recombinant retrovirus vector was produced for a growth rate assay, and a higher growth rate was observed in C7orf24-expressing cells compared with the controls. Six kinds of small interfering RNAs (siRNAs) were then produced, and C7orf24-siRNA#5 showed a strong knockdown effect on protein expression and significant antiproliferative effects on cancer cell lines were demonstrated by the MTT assay. Therefore, C7orf24 may have an important role in cancer cell proliferation, and may be an appropriate therapeutic target molecule against cancer.
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