• Title/Summary/Keyword: bladder cancer

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Oxidative Stress Induces Hypomethylation of LINE-1 and Hypermethylation of the RUNX3 Promoter in a Bladder Cancer Cell Line

  • Wongpaiboonwattana, Wikrom;Tosukhowong, Piyaratana;Dissayabutra, Thasinas;Mutirangura, Apiwat;Boonla, Chanchai
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3773-3778
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    • 2013
  • Increased oxidative stress and changes in DNA methylation are frequently detected in bladder cancer patients. We previously demonstrated a relationship between increased oxidative stress and hypomethylation of the transposable long-interspersed nuclear element-1 (LINE-1). Promoter hypermethylation of a tumor suppressor gene, runt-related transcription factor 3 (RUNX3), may also be associated with bladder cancer genesis. In this study, we investigated changes of DNA methylation in LINE-1 and RUNX3 promoter in a bladder cancer cell (UM-UC-3) under oxidative stress conditions, stimulated by challenge with $H_2O_2$ for 72 h. Cells were pretreated with an antioxidant, tocopheryl acetate for 1 h to attenuate oxidative stress. Methylation levels of LINE-1 and RUNX3 promoter were measured by combined bisulfite restriction analysis PCR and methylation-specific PCR, respectively. Levels of LINE-1 methylation were significantly decreased in $H_2O_2$-treated cells, and reestablished after pretreated with tocopheryl acetate. Methylation of RUNX3 promoter was significantly increased in cells exposed to $H_2O_2$. In tocopheryl acetate pretreated cells, it was markedly decreased. In conclusion, hypomethylation of LINE-1 and hypermethylation of RUNX3 promoter in bladder cancer cell line was experimentally induced by reactive oxygen species (ROS). The present findings support the hypothesis that oxidative stress promotes urothelial cell carcinogenesis through modulation of DNA methylation. Our data also imply that mechanistic pathways of ROS-induced alteration of DNA methylation in a repetitive DNA element and a gene promoter might differ.

Prognostic Value of Tissue Vascular Endothelial Growth Factor Expression in Bladder Cancer: a Meta-analysis

  • Huang, Yu-Jing;Qi, Wei-Xiang;He, Ai-Na;Sun, Yuan-Jue;Shen, Zan;Yao, Yang
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.645-649
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    • 2013
  • Objective: The prognostic role of vascular endothelial growth factor (VEGF) in bladder cancer remains controversial. This meta-analysis aimed to explore any association between overexpression and survival outcomes. Methods: We systematically searched for studies investigating the relationships between VEGF expression and outcome of bladder cancer patients. Study quality was assessed using the Newcastle-Ottawa Scale. After careful review, survival data were extracted from eligible studies. A meta-analysis was performed to generate combined hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS). Results: A total of 1,285 patients from 11 studies were included in the analysis. Our results showed that tissue VEGF overexpression in patients with bladder cancer was associated with poor prognosis in terms of OS (HR, 1.843; 95% CI, 1.231-2.759; P = 0.003), DFS (HR, 1.498; 95% CI, 1.255-1.787; P = 0.000) and DSS (HR, 1.562; 95% CI, 0.996-1.00; P = 0.052), though the difference for DSS was not statistically significant. In addition, there was no evidence of publication bias as suggested by Begg's and Egger's tests except for DFS (Begg's test, P = 0.221; Egger's test, P = 0.018). Conclusion: The present meta-analysis indicated elevated VEGF expression to be associated with a poor prognosis in patients with bladder cancer.

Low Microsomal Epoxide Hydrolase Expression is Associated with Bladder Carcinogenesis and Recurrence

  • Zhang, Zhe;Yu, Xiu-Yue;Zhang, Guo-Jun;Guo, Kun-Feng;Kong, Chui-Ze
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.2
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    • pp.521-525
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    • 2012
  • Microsomal epoxide hydrolase (mEH) plays a significant role in the metabolism of numerous xenobiotics and is associated with several forms of cancer. Here, we investigated the role of mEH expression in bladder carcinogenesis, subsequent progression and recurrence. The expression of mEH was analyzed by Western blot in 50 bladder urothelial carcinoma and 20 normal epithelial tissues. There was a significantly higher mEH expression in the normal epithelium (P<0.05) and mEH expression was lower in high stage than in low stage tumors (P<0.05). Further, immunohistochmistry in 106 bladder urothelial carcinoma demonstrated mEH expression to be negatively correlated with histological grade, pT stage and recurrence (P<0.05). These findings suggest the important role of mEH in bladder carcinogenesis, cancer development and recurrence, providing support for efforts to develop mEH-based gene therapy.

Can Recurrence and Progression be Predicted by HYAL-1 Expression in Primary T1 Bladder Cancer?

  • Mammadov, Elnur;Aslan, Guven;Tuna, Burcin;Bozkurt, Ozan;Yorukoglu, Kutsal
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10401-10405
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    • 2015
  • Background: Molecular prognostic markers have been under investigation for the last decade and no validated marker to date has been proven to be used in daily clinical practice for urinary bladder cancers. The aim of the present study is to evaluate the significance of HYAL-1 expression in prediction of recurrence and progression in pT1 urothelial carcinomas. Materials and Methods: Eighty-nine urothelial carcinoma cases staged as T1 according to 2004 WHO classification were studied. Representative sections from every case were stained immunohistochemically for HYAL-1 and scored between 0 and +3, according to staining density, and graded as low and high for the scores 0-1 and 2-3, respectively. Results: Of the 89 pT1 bladder cancer patients, HYAL-1 expression was high in 92.1% (82 patients; 72 patients +3 and 10 patients +2) and low in 7.9% (only 7 patients; 6 patients +1 and 1 patient 0) of the cases. Of the 89 patients, 38 (42.7%) had recurrence and 22 (24.7%) showed progression. HYAL-1 staining did not show significant characteristics for tumor grade, accompanying CIS, multiplicity, tumor size, age and sex. HYAL-1 expression did not have any prognostic value in estimating recurrence or progression. Conclusions: HYAL-1 expression was found to be high, but did not have any prognostic importance in T1 bladder urothelial carcinomas.

Functional RsaI/PstI Polymorphism in Cytochrome P450 2E1 Contributes to Bladder Cancer Susceptibility: Evidence from a Meta-analysis

  • Deng, Xiao-Dong;Gao, Qin;Zhang, Bo;Zhang, Li-Xia;Zhang, Wei;Er, Zhe-Er Mu;Xie, Ying;Ma, Ying;Liu, Yun
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4977-4982
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    • 2014
  • Background: Cytochrome P450 2E1 (CYP2E1) might be involved in the development of bladder cancer. However, previous studies of any association between CYP2E1 RsaI/PstI polymorphism and bladder cancer risk have yielded conflicting results. In this study, we performed a more precise estimation of the relationship by a meta-analysis based on the currently available evidence from the literature. Method: To assess the effect of CYP2E1 RsaI/PstI polymorphism on bladder cancer susceptibility, a meta-analysis of 6 available studies with 1,510 cases and 1,560 controls were performed through Feb 2014. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of association for CYP2E1 RsaI/PstI polymorphism under different genetic models. Results: When available studies were pooled into the meta-analysis, we found that the C1C2 and C2C2 genotypes of CYP2E1 RsaI/PstI polymorphism significantly decreased bladder cancer risk under different genetic models (heterozygote: OR=0.766, 95%CI=0.613-0.957, $P_{OR}$=0.019; homozygote: OR=0.51, 95%CI=0.303-0.858, $P_{OR}$=0.011; dominant: OR=0.733, 95%CI=0.593-0.905, $P_{OR}$=0.004; recessive: OR=0.565, 95%CI=0.337-0.947, $P_{OR}$=0.030). Subgroup analysis indicated that C2C2 genotype was significantly associated with decreased bladder cancer risk under the homozygote genetic model in Caucasians. There was no evidence of heterogeneity or publication bias. Conclusions: The current meta-analysis suggested that the CYP2E1 RsaI/PstI polymorphism might be associated with bladder cancer susceptibility, especially in Caucasians. Further studies are needed to validate the above conclusion.

Prognostic Significance of Nestin Expression in pT1 High-Grade Bladder Urothelial Carcinoma Patients Treated with Intravesical BCG

  • Sen, Volkan;Bozkurt, Ozan;Demir, Omer;Tuna, Burcin;Yorukoglu, Kutsal;Ellidokuz, Hulya;Mungan, Ugur
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10813-10817
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    • 2015
  • Background: Possible roles of nestin expression in terms of predicting intravesical BCG therapy response in T1 high grade bladder cancer patients were investigated. Materials and Methods: T1 high grade bladder cancer patients who were treated with intravesical BCG between 1990-2009 were included. Immunohistochemical staining for nestin expression was performed. Nestin(+) and nestin(-) patients were compared in terms of recurrence and progression rates. Results: Sixty-three patients were included and median follow-up time was twenty-five months. After staining; 33 patients (52.4%) were classified as nestin (+) and 30 (47.6%) as (-). Nestin (+) patients were more likely to recur compared to nestin (-) patients (60.6% vs. 30%, p<0.05). Progression rates were also higher in nestin (+) patients, although this result did not reach statistical significance (15.2 % vs. 10 %, p=0.710). Conclusions: Nestin expression, which seems effective in predicting recurrence, appears to have a potential role in the urothelial carcinoma tumorigenesis. Patients with high grade bladder cancer and positive nestin expression need close follow-up and might be informed about more tendency to recur. Further comprehensive studies including larger patient cohorts may clarify the role of nestin in bladder cancer.

Urothelial Carcinoma of the Bladder: Radiologic Perspective (방광 요로상피세포암: 영상의학적 관점)

  • Dong Won Kim;Seong Kuk Yoon;Sang Hyeon Kim
    • Journal of the Korean Society of Radiology
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    • v.82 no.5
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    • pp.1033-1052
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    • 2021
  • Bladder cancer is a relatively common cancer type, with a high recurrence rate, that can be often encountered in the imaging study. Accurate diagnosis and staging have a significant impact on determining treatment and evaluating prognosis. Bladder cancer has been evaluated by transurethral resection of bladder tumor for clinical staging and treatment, but it is often understaged when compared with final pathologic result by radical cystectomy. If the location, size, presence of muscle invasion, lymph node metastasis, distant metastasis, and presence of upper urinary tract cancer can be accurately diagnosed and evaluated in an imaging study, it can be treated and managed more appropriately. For an accurate diagnosis, radiologists who evaluate the images must be aware of the characteristics of bladder cancer as well as its types, imaging techniques, and limitations of imaging studies. Recent developments in MRI with functional imaging have improved the quality of bladder imaging and the evaluation of cancer. In addition, the Vesical Imaging Reporting and Data System was published to objectively assess the possibility for muscle invasion of cancer. Radiologists need to know the types of bladder cancer treatment and how to evaluate the changes after treatment. In this article, the characteristics of bladder urothelial carcinoma, various imaging studies, and findings are reviewed.

Clinical Study for the One Case that Sequela of Bladder Cancer Patient Treatments by Korean Medicine (방광암 후유증 환자 치험 1례)

  • Cho, Seong-Hee;Song, Yu-Rim
    • The Journal of Korean Obstetrics and Gynecology
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    • v.28 no.2
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    • pp.156-164
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    • 2015
  • Objectives : This study aims to report the effect of Korean medicine treatment on Sequela of Bladder Cancer. Methods : The patient was treated with korean medicine of Paljeongsan-gamibang, acupuncture at Qihai (CV6), Guanyuan (CV4), Qugu (CV2), Hyeolhae (SP10), Sameumgyo (SP6) and we evaluated treatment effects by visual analogue scale (VAS) and urine analysis (UA) finding. Results : After treatments, the symptoms such as perineal pain, painful urination, dysuria, anorexia were improved and taking number of narcotic analgesic was reduced. Conclusions : This clinical study suggests that korean medicine treatment shows possibility to care for sequela of bladder cancer patient.

Cancer Risks among Welders and Occasional Welders in a National Population-Based Cohort Study: Canadian Census Health and Environmental Cohort

  • MacLeod, Jill S.;Harris, M. Anne;Tjepkema, Michael;Peters, Paul A.;Demers, Paul A.
    • Safety and Health at Work
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    • v.8 no.3
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    • pp.258-266
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    • 2017
  • Background: Welders are exposed to many known and suspected carcinogens. An excess lung cancer risk among welders is well established, but whether this is attributable to welding fumes is unclear. Excess risks of other cancers have been suggested, but not established. We investigated welding cancer risks in the population-based Canadian Census Health and Environmental Cohort. Methods: Among 1.1 million male workers, 12,845 welders were identified using Standard Occupational Classification codes and followed through retrospective linkage of 1991 Canadian Long Form Census and Canadian Cancer Registry (1992-2010) records. Hazard ratios (HRs) were calculated using Cox proportional hazards models based on estimated risks of lung cancer, mesothelioma, and nasal, brain, stomach, kidney, and bladder cancers, and ocular melanoma. Lung cancer histological subtypes and risks by industry group and for occasional welders were examined. Some analyses restricted comparisons to blue-collar workers to minimize effects of potential confounders. Results: Among welders, elevated risks were observed for lung cancer [HR: 1.16, 95% confidence interval (CI): 1.03-1.31], mesothelioma (HR: 1.78, 95% CI: 1.01-3.18), bladder cancer (HR: 1.40, 95% CI: 1.15-1.70), and kidney cancer (HR: 1.30, 95% CI: 1.01-1.67). When restricted to blue-collar workers, lung cancer and mesothelioma risks were attenuated, while bladder and kidney cancer risks increased. Conclusion: Excess risks of lung cancer and mesothelioma may be partly attributable to factors including smoking and asbestos. Welding-specific exposures may increase bladder and kidney cancer risks, and particular sources of exposure should be investigated. Studies that are able to disentangle welding effects from smoking and asbestos exposure are needed.

Epidemiology, Incidence and Mortality of Bladder Cancer and their Relationship with the Development Index in the World

  • Mahdavifar, Neda;Ghoncheh, Mahshid;Pakzad, Reza;Momenimovahed, Zohre;Salehiniya, Hamid
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.1
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    • pp.381-386
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    • 2016
  • Background: Bladder cancer is an international public health problem. It is the ninth most common cancer and the fourteenth leading cause of death due to cancer worldwide. Given aging populations, the incidence of this cancer is rising. Information on the incidence and mortality of the disease, and their relationship with level of economic development is essential for better planning. The aim of the study was to investigate bladder cancer incidence and mortality rates, and their relationship with the the Human Development Index (HDI) in the world. Materials and Methods: Data were obtained from incidence and mortality rates presented by GLOBOCAN in 2012. Data on HDI and its components were extracted from the global bank site. The number and standardized incidence and mortality rates were reported by regions and the distribution of the disease were drawn in the world. For data analysis, the relationship between incidence and death rates, and HDI and its components was measured using correlation coefficients and SPSS software. The level of significance was set at 0.05. Results: In 2012, 429,793 bladder cancer cases and 165,084 bladder death cases occurred in the world. Five countries that had the highest age-standardized incidence were Belgium 17.5 per 100,000, Lebanon 16.6/100,000, Malta 15.8/100,000, Turkey 15.2/100,000, and Denmark 14.4/100,000. Five countries that had the highest age-standardized death rates were Turkey 6.6 per 100,000, Egypt 6.5/100,000, Iraq 6.3/100,000, Lebanon 6.3/100,000, and Mali 5.2/100,000. There was a positive linear relationship between the standardized incidence rate and HDI (r=0.653, P<0.001), so that there was a positive correlation between the standardized incidence rate with life expectancy at birth, average years of schooling, and the level of income per person of population. A positive linear relationship was also noted between the standardized mortality rate and HDI (r=0.308, P<0.001). There was a positive correlation between the standardized mortality rate with life expectancy at birth, average years of schooling, and the level of income per person of population. Conclusions: The incidence of bladder cancer in developed countries and parts of Africa was higher, while the highest mortality rate was observed in the countries of North Africa and the Middle East. The program for better treatment in developing countries to reduce mortality from the cancer and more detaiuled studies on the etiology of are essential.