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  1. Bladder Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing bladder cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  2. Tetrachloroethylene exposure and bladder cancer risk

    DEFF Research Database (Denmark)

    Vlaanderen, Jelle; Straif, Kurt; Ruder, Avima

    2014-01-01

    -analysis demonstrates an increased risk of bladder cancer in dry cleaners, reported in both cohort and case-control studies, and some evidence for an exposure-response relationship. Although dry cleaners incur mixed exposures, tetrachloroethylene could be responsible for the excess risk of bladder cancer because...... it is the primary solvent used and it is the only chemical commonly used by dry cleaners that is currently identified as a potential bladder carcinogen. Relatively crude approaches in exposure assessment in the studies of "tetrachloroethylene-exposed workers" may have attenuated the relative risks....

  3. Recurrent urinary tract infection and risk of bladder cancer in the Nijmegen bladder cancer study

    NARCIS (Netherlands)

    Vermeulen, S.; Hanum, N.; Grotenhuis, A.J.; Castano-Vinyals, G.; Heijden, A.G. van der; Aben, K.K.H.; Mysorekar, I.U.; Kiemeney, L.A.L.M.

    2015-01-01

    BACKGROUND: Controversy exists on whether urinary tract infection (UTI) is a risk factor for urinary bladder cancer (UBC). Here, the association is investigated using data from one of the largest bladder cancer case-control studies worldwide. METHODS: Information on (i) history and age at onset of r

  4. What Are the Risk Factors for Bladder Cancer?

    Science.gov (United States)

    ... Food and Drug Administration (FDA), use of the diabetes medicine pioglitazone (Actos) for more than one year may be linked with an increased risk of bladder cancer. This possible link is still an area of ...

  5. Schistosomiasis and the risk of bladder cancer in Alexandria, Egypt.

    OpenAIRE

    Bedwani, R.; Renganathan, E.; El Kwhsky, F.; Braga, C.; Abu Seif, H. H.; Abul Azm, T.; Zaki, A.; De Franceschi, S.; Boffetta, P; La Vecchia, C.

    1998-01-01

    The relationship between history of schistosomiasis and bladder cancer risk was investigated using data from a case-control study conducted between January 1994 and July 1996 in Alexandria, Egypt. Cases were 190 subjects with incident, histologically confirmed invasive cancer of the bladder, and controls were 187 subjects admitted to hospital for acute, non-neoplastic, non-urinary tract conditions. Eighty-six cases (45%) vs 69 controls (37%) reported a history of urinary schistosomiasis. The ...

  6. Bladder cancer, a review of the environmental risk factors

    Directory of Open Access Journals (Sweden)

    Letašiová Silvia

    2012-06-01

    Full Text Available Abstract Background Many epidemiological studies and reviews have been performed to identify the causes of bladder cancer. The aim of this review is to investigate the links between various environmental risk factors and cancer of the bladder. Methods A systematic literature search was performed using PubMed, Science Direct, Scopus, Scholar Google and Russian Google databases to identify reviews and epidemiological studies on bladder cancer risk factors associated with the environment published between 1998 and 2010. Only literature discussing human studies was considered. Results Smoking, mainly cigarette smoking, is a well known risk factor for various diseases, including bladder cancer. Another factor strongly associated with bladder cancer is exposure to arsenic in drinking water at concentrations higher than 300 µg/l. The most notable risk factor for development of bladder cancer is occupational exposure to aromatic amines (2-naphthylamine, 4-aminobiphenyl and benzidine and 4,4'-methylenebis(2-chloroaniline, which can be found in the products of the chemical, dye and rubber industries as well as in hair dyes, paints, fungicides, cigarette smoke, plastics, metals and motor vehicle exhaust. There are also data suggesting an effect from of other types of smoking besides cigarettes (cigar, pipe, Egyptian waterpipe, smokeless tobacco and environmental tobacco smoking, and other sources of arsenic exposure such as air, food, occupational hazards, and tobacco. Other studies show that hairdressers and barbers with occupational exposure to hair dyes experience enhanced risk of bladder cancer. For example, a study related to personal use of hair dyes demonstrates an elevated bladder cancer risk for people who used permanent hair dyes at least once a month, for one year or longer. Conclusion Smoking, in particular from cigarettes, exposure to arsenic in drinking water, and occupational exposure to aromatic amines and 4,4'-methylenebis(2-chloroaniline

  7. Epidemiology and risk factors of urothelial bladder cancer

    NARCIS (Netherlands)

    Burger, M.; Catto, J.W.; Dalbagni, G.; Grossman, H.B.; Herr, H.; Karakiewicz, P.; Kassouf, W.; Kiemeney, L.A.L.M.; La Vecchia, C.; Shariat, S.; Lotan, Y.

    2013-01-01

    CONTEXT: Urothelial bladder cancer (UBC) is a disease of significant morbidity and mortality. It is important to understand the risk factors of this disease. OBJECTIVE: To describe the incidence, prevalence, and mortality of UBC and to review and interpret the current evidence on and impact of the r

  8. Schistosomiasis and the risk of bladder cancer in Alexandria, Egypt.

    Science.gov (United States)

    Bedwani, R; Renganathan, E; El Kwhsky, F; Braga, C; Abu Seif, H H; Abul Azm, T; Zaki, A; Franceschi, S; Boffetta, P; La Vecchia, C

    1998-04-01

    The relationship between history of schistosomiasis and bladder cancer risk was investigated using data from a case-control study conducted between January 1994 and July 1996 in Alexandria, Egypt. Cases were 190 subjects with incident, histologically confirmed invasive cancer of the bladder, and controls were 187 subjects admitted to hospital for acute, non-neoplastic, non-urinary tract conditions. Eighty-six cases (45%) vs 69 controls (37%) reported a history of urinary schistosomiasis. The corresponding multivariate odds ratio (OR) of bladder cancer -- after allowance for age, sex, education, smoking, other urinary infections and high-risk occupations -- was 1.72 (95% confidence interval (CI) 1.0-2.9). The ORs were 0.22 (95% CI 0.1-0.4) for intestinal schistosomiasis and 0.32 (95% CI 0.1-1.9) for schistosomiasis of other types. The OR for urinary schistosomiasis was higher in subjects who were younger at first diagnosis (OR of 3.3 for or = 35 years). The ORs were 15.8 for male ever-smokers with a history of urinary schistosomiasis, compared with never-smokers without such a history, and 3.2 for men ever-infected with urinary Schistosoma haematobium and ever-employed in high-risk occupations, compared with those never-infected and with no high-risk occupational history. This study confirms that clinical history of urinary schistosomiasis is significantly, but modestly, associated with increased bladder cancer risk, explaining some 16% of bladder cancer cases in this Egyptian population.

  9. [Benzidine dyes and risk of bladder cancer].

    Science.gov (United States)

    Miyakawa, M; Yoshida, O

    1989-12-01

    Until the early 1970's there was little concern about dyes which contain benzidine as an integral part of their chemical structure. Furthermore, use of the finished dyes was not considered dangerous. To ascertain whether azo dyes are associated with risk of development of bladder tumors in workers who handpaint Yuzen-type silk kimonos in Kyoto, we investigated the disintegration of dyes to benzidine. In these studies, we found that in rats and mice benzidine-based dyes are metabolized to benzidine and that the azo linkage of benzidine dyes is reduced by Escherichia coli and soil bacteria. These experimental findings were reported previously. In this report, we outline an approach to these studies. Many of the dyes used to color paper, textiles, lipstick, bait used by fishermen, as well as hair dyes, and dyes used in research, for pharmaceutical products, and by defence personnel for the detection of liquid chemical warfare agents, have been shown to be potentially mutagenic or carcinogenic. We review the literature on these dyes.

  10. AB267. Association of genetic polymorphism of CCNE1 and RIP2 with bladder cancer risk

    OpenAIRE

    Liang, Enli

    2016-01-01

    Background A single nucleotide polymorphism is identified at CCNE1 and RIP2. We evaluated the relationship between the CCNE1 or RIP2 and the risk, clinic stage and pathologic grade of bladder cancer. Methods Peripheral venous blood samples were obtained from 176 patients with bladder cancer and 210 controls with no cancers of any kinds. The diagnoses, pathological stage of bladder cancer were all determined according to the pathological reports of transurethral bladder cancer resection and ra...

  11. Consumption of vegetables and fruit and the risk of bladder cancer in the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Büchner, F.L.; Bueno de Mesquita, H.B.; Ros, M.M.; Kampman, E.

    2009-01-01

    Previous epidemiologic studies found inconsistent associations between vegetables and fruit consumption and the risk of bladder cancer. We therefore investigated the association between vegetable and fruit consumption and the risk of bladder cancer among participants of the European Prospective Inve

  12. polymorphisms, occupational and environmental exposures and risk of bladder cancer

    OpenAIRE

    Pavanello, Sofia; Mastrangelo, Giuseppe; Placidi, Donatella; Campagna, Marcello; Pulliero, Alessandra; Carta, Angela; Arici, Cecilia; Porru, Stefano

    2010-01-01

    Abstract Cytochrome P4501A2 (CYP1A2) is a key enzyme for activation of bladder carcinogens. Polymorphisms in the 5?-noncoding promoter region of CYP1A2 gene [mainly ?2467T/delT(rs35694136) and ?163C/A(rs762551)], are crucial in modifying CYP1A2 activity in smokers. Within the framework of a hospital-based case/control study, we investigated the relationship between CYP1A2 polymorphisms, occupational/environmental exposures and bladder cancer (BC) risk. The study population included...

  13. Pioglitazone use and the risk of bladder cancer.

    Science.gov (United States)

    Kuo, Hsin-Wei; Tiao, Mao-Meng; Ho, Shu-Chen; Yang, Chun-Yuh

    2014-02-01

    This study aimed to identify the risk association between pioglitazone exposure and bladder cancer. A nested case-control study was performed using a representative database randomly sampled from National Health Insurance enrollees. The source cohort consisted of newly diagnosed diabetic patients from 1997 to 2009. Cases were identified as those with a diagnosis of bladder cancer from 2002 to 2009. For each case, four matched control individuals were randomly selected. A multiple logistic regression model was used to estimate the relative magnitude of risk in relation to the use of pioglitazone. In total, 259 cases and 1036 controls were identified. The prevalent use of pioglitazone is similar in cases and controls (adjusted odds ratio, 1.20; 95% confidence interval, 0.58-2.49). Compared to nonusers, these values were 1.08 (0.41-2.88) for those with cumulative pioglitazone use ≤ 8268 mg and 1.35 (0.48-3.79) for those with cumulative pioglitazone use > 8268 mg. This study does not provide support for the risk association between pioglitazone exposure and bladder cancer. Further confirmation is needed due to the limitation of small case number with relatively shorter exposure duration and lower cumulative dose.

  14. Risk of bladder cancer in patients with diabetes

    DEFF Research Database (Denmark)

    Goossens, Maria E; Zeegers, Maurice P; Bazelier, Marloes T;

    2015-01-01

    OBJECTIVE: The objective of this study was to examine the association between diabetes, and both urinary bladder cancer (UBC) risk and mortality. METHODS: We conducted a retrospective cohort study using data from the UK Clinical Practice Research Datalink (CPRD) linked to the Office of National...... Statistics (ONS). Patients diagnosed with diabetes mellitus type 1 or 2, or using antidiabetic drugs (ADDs), were compared to matched non-diabetic controls. Cox proportional hazards models were used to estimate the risk and mortality of UBC. We adjusted for age, sex, smoking status and body mass index...... were similar if we restricted our analysis to an inception cohort. We noticed a small increased risk during the first year after diagnosis (HR=1.26 (95% CI 1.05 to 1.52)), which could be explained by detection bias. There was no influence of the severity of diabetes as measured by the glycated...

  15. Consumption of raw cruciferous vegetables is inversely associated with bladder cancer risk.

    Science.gov (United States)

    Tang, Li; Zirpoli, Gary R; Guru, Khurshid; Moysich, Kirsten B; Zhang, Yuesheng; Ambrosone, Christine B; McCann, Susan E

    2008-04-01

    Cruciferous vegetables contain isothiocyanates, which show potent chemopreventive activity against bladder cancer in both in vitro and in vivo studies. However, previous epidemiologic studies investigating cruciferous vegetable intake and bladder cancer risk have been inconsistent. Cooking can substantially reduce or destroy isothiocyanates, and could account for study inconsistencies. In this hospital-based case-control study involving 275 individuals with incident, primary bladder cancer and 825 individuals without cancer, we examined the usual prediagnostic intake of raw and cooked cruciferous vegetables in relation to bladder cancer risk. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with unconditional logistic regression, adjusting for smoking and other bladder cancer risk factors. We observed a strong and statistically significant inverse association between bladder cancer risk and raw cruciferous vegetable intake (adjusted OR for highest versus lowest category = 0.64; 95% CI, 0.42-0.97), with a significant trend (P = 0.003); there were no significant associations for fruit, total vegetables, or total cruciferous vegetables. The associations observed for total raw crucifers were also observed for individual raw crucifers. The inverse association remained significant among current and heavy smokers with three or more servings per month of raw cruciferous vegetables (adjusted ORs, 0.46 and 0.60; 95% CI, 0.23-0.93 and 0.38-0.93, respectively). These data suggest that cruciferous vegetables, when consumed raw, may reduce the risk of bladder cancer, an effect consistent with the role of dietary isothiocyanates as chemopreventive agents against bladder cancer.

  16. Occupation and Risk of Bladder Cancer in Nordic Countries

    DEFF Research Database (Denmark)

    Hadkhale, Kishor; Martinsen, Jan Ivar; Weiderpass, Elisabete;

    2016-01-01

    OBJECTIVE: The purpose of the study was to describe the variation of bladder cancer incidence according to occupational categories in the Nordic countries. METHODS: The study cohort comprised 15 million individuals older than 30 years who participated in one or more population censuses in 1960......, 1970, 1980/1981, and/or 1990. Standardized incidence ratios (SIRs) were estimated for 53 occupational categories. RESULTS: Significantly increased SIRs were observed among tobacco workers (1.57; 95% confidence interval [CI] 1.24 to 1.96), chimney sweeps (1.48; 95% CI 1.21 to 1.80), waiters (1.43; 95......% CI 1.33 to 1.53), hairdressers (1.28; 95% CI 1.18 to 1.40), seamen (1.22; 95% CI 1.16 to 1.30), printers (1.21; 95% CI 1.14 to 1.30), and plumbers (1.20; 95% CI 1.13 to 1.30). A significantly decreased risk of bladder cancer was observed among gardeners (0.78, 0.75 to 0.80), forestry workers (0...

  17. Controversies Related to Diabetes and Risk of Bladder Cancer.

    Science.gov (United States)

    Spradling, Kyle; Youssef, Ramy F

    2016-03-15

    In recent years, a growing number of case-control and cohort studies have suggested that patients with diabetes mellitus (DM) may have a higher risk of developing bladder cancer (BC). However, the body of evidence linking DM and BC is controversial and largely composed of observational studies with significant heterogeneity in study design. In this review, we outline the current body of evidence associating DM with BC. We also highlight the evidence surrounding the relationship between BC and two antidiabetic medications, metformin and pioglitazone. Currently, not enough evidence is available to decisively conclude that DM is associated with an increased risk for development of BC. Similarly, the current body of evidence is inadequate to establish a causal relationship between pioglitazone and BC nor a protective relationship between metformin and BC.

  18. Polymorphisms in DNA repair genes, smoking, and bladder cancer risk: findings from the International Consortium of Bladder Cancer

    Science.gov (United States)

    Stern, Mariana C.; Lin, Jie; Figueroa, Jonine D.; Kelsey, Karl T.; Kiltie, Anne E.; Yuan, Jian-Min; Matullo, Giuseppe; Fletcher, Tony; Benhamou, Simone; Taylor, Jack A.; Placidi, Donatella; Zhang, Zuo-Feng; Steineck, Gunnar; Rothman, Nathaniel; Kogevinas, Manolis; Silverman, Debra; Malats, Nuria; Chanock, Stephen; Wu, Xifeng; Karagas, Margaret R.; Andrew, Angeline S.; Nelson, Heather H.; Bishop, D. Timothy; Sak, Sei Chung; Choudhury, Ananya; Barrett, Jennifer H; Elliot, Faye; Corral, Román; Joshi, Amit D.; Gago-Dominguez, Manuela; Cortessis, Victoria K.; Xiang, Yong-Bing; Vineis, Paolo; Sacerdote, Carlotta; Guarrera, Simonetta; Polidoro, Silvia; Allione, Alessandra; Gurzau, Eugen; Koppova, Kvetoslava; Kumar, Rajiv; Rudnai, Peter; Porru, Stefano; Carta, Angela; Campagna, Marcello; Arici, Cecilia; Park, SungShim Lani; Garcia-Closas, Montserrat

    2009-01-01

    Tobacco smoking is the most important and well-established bladder cancer risk factor, and a rich source of chemical carcinogens and reactive oxygen species that can induce damage to DNA in urothelial cells. Therefore, common variation in DNA repair genes might modify bladder cancer risk. In this study we present results from meta- and pooled analyses conducted as part of the International Consortium of Bladder Cancer. We included data on 10 single nucleotide polymorphisms corresponding to 7 DNA repair genes from 13 studies. Pooled- and meta-analyses included 5,282 cases and 5,954 controls of non-Latino white origin. We found evidence for weak but consistent associations with ERCC2 D312N (rs1799793) (per allele OR = 1.10; 95% CI = 1.01–1.19; p = 0.021), NBN E185Q (rs1805794) (per allele OR = 1.09; 95% CI = 1.01–1.18; p = 0.028), and XPC A499V (rs2228000) (per allele OR = 1.10; 95% CI = 1.00–1.21, p = 0.044). The association with NBN E185Q was limited to ever smokers (interaction p = 0.002), and was strongest for the highest levels of smoking dose and smoking duration. Overall, our study provides the strongest evidence to date for a role of common variants in DNA repair genes in bladder carcinogenesis. PMID:19706757

  19. Phase 2 study of adjuvant intravesical instillations of apaziquone for high risk nonmuscle invasive bladder cancer.

    NARCIS (Netherlands)

    Hendricksen, K.; Cornel, E.B.; Reijke, T.M. de; Arentsen, H.C.; Chawla, S.; Witjes, J.A.

    2012-01-01

    PURPOSE: We studied the safety and efficacy of multiple adjuvant apaziquone instillations in patients with high risk nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Patients with high risk nonmuscle invasive urothelial carcinoma of the bladder underwent transurethral resection of all bladd

  20. Cigarette Smoking and the Risk of Bladder Cancer in Men and Women

    Directory of Open Access Journals (Sweden)

    Quirk Jeffrey T

    2004-09-01

    Full Text Available Abstract Although cigarette smoking is a principal risk factor for bladder cancer in both men and women, few studies have statistically evaluated whether gender modifies the effect of smoking on bladder cancer risk. We initiated the present case-control study at Roswell Park Cancer Institute in Buffalo, New York, U.S., to provide further data on this important issue. We observed similar risk estimates for men and women with comparable smoking exposures, but did not observe a statistically significant interaction between gender and lifetime smoking exposure. We conclude that cigarette smoking is a major risk factor for bladder cancer in both sexes, but that gender does not modify the effect of smoking on bladder cancer risk.

  1. High risk bladder cancer: current management and survival

    Directory of Open Access Journals (Sweden)

    Anna M. Leliveld

    2011-04-01

    Full Text Available PURPOSE: To evaluate the pattern of care in patients with high risk non muscle invasive bladder cancer (NMIBC in the Comprehensive Cancer Center North-Netherlands (CCCN and to assess factors associated with the choice of treatment, recurrence and progression free survival rates. MATERIALS AND METHODS: Retrospective analysis of 412 patients with newly diagnosed high risk NMIBC. Clinical, demographic and follow-up data were obtained from the CCCN Cancer Registry and a detailed medical record review. Uni and multivariate analysis was performed to identify factors related to choice of treatment and 5 year recurrence and progression free survival. RESULTS: 74/412 (18% patients with high risk NMIBC underwent a transurethral resection (TUR as single treatment. Adjuvant treatment after TUR was performed in 90.7% of the patients treated in teaching hospitals versus 71.8 % in non-teaching hospitals (p 80 years OR 0.1 p = 0.001 and treatment in non-teaching hospitals (OR 0.25; p < 0.001 were associated with less adjuvant treatment after TUR. Tumor recurrence occurred in 191/392 (49% and progression in 84 /392 (21.4% patients. The mean 5-years progression free survival was 71.6% (95% CI 65.5-76.8. CONCLUSION: In this pattern of care study in high risk NMIBC, 18% of the patients were treated with TUR as single treatment. Age and treatment in non-teaching hospitals were associated with less adjuvant treatment after TUR. None of the variables sex, age, comorbidity, hospital type, stage and year of treatment was associated with 5 year recurrence or progression rates.

  2. Use of thiazolidinediones and risk of bladder cancer

    DEFF Research Database (Denmark)

    Bazelier, Marloes T; de Vries, Frank; Vestergaard, Peter;

    2013-01-01

    ) of bladder cancer were estimated using Cox proportional hazards models. Time-dependent adjustments were made for age, comorbidity, and drug use. Four different treatment stages were defined: current use of either a biguanide or a sulfonylureum (stage 1), current use of a biguanide and a sulfonylureum...

  3. Bladder Cancer Advocacy Network

    Science.gov (United States)

    ... future bladder cancer research through the Patient Survey Network. Read More... The JPB Foundation 2016 Bladder Cancer ... 2016 Young Investigator Awardees The Bladder Cancer Advocacy Network (BCAN) has announced the recipients of the 2016 ...

  4. High-risk bladder cancer: improving outcomes with perioperative chemotherapy

    Directory of Open Access Journals (Sweden)

    Daniel Y.C. Heng

    2011-12-01

    Full Text Available Despite treatment with radical cystectomy and pelvic lymph node dissection, muscle invasive bladder cancer has a relapse rate of 50%. Patients can develop regionally advanced or metastatic disease that ultimately leads to death. The addition of neoadjuvant or adjuvant chemotherapy to reduce the risk of relapse and death has been extensively studied over the past two decades. Two contemporary trials coupled with a recent meta-analysis evaluating neoadjuvant chemotherapy demonstrated a modest but real improvement in overall survival. This has made neoadjuvant chemotherapy a standard of care. Clinical trials evaluating adjuvant chemotherapy in patients with high-risk disease have been plagued with statistical flaws and have, therefore, been unable to define the survival impact of this approach. It is hoped that ongoing adjuvant trials that are powered to detect small but meaningful clinical differences will clarify the benefit of chemotherapy after cystectomy. Since there are theoretical advantages and disadvantages to each of these approaches, both are widely used in North America. The evidence behind each approach and potential future developments in this field will be described.

  5. GENETIC RISK MARKERS FOR SUPERFICIAL AND INVASIVE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    V. N. Pavlov

    2011-01-01

    Full Text Available To reveal possible associations of the polymorphic variants of the cytochrome P450 and enzymes glutathione-S-transferase genes with the risk for bladder cancer (BC, the authors analyzed the frequency of genotypes and alleles at the polymorphic loci of the CYP1A1 (A2454G, GSTM1 (del, and GSTP1 (A313G genes in 208 patients diagnosed as having BC (104 patients with invasive BC and 104 with superficial BC and in 367 patients without identified oncopathology. The *1A*2C (OR = 3.42 and *2C*2С (OR = 6.98 genotypes, *2C (OR = 3.73 allele of the CYP1A1 gene and the GG (OR = 2.53 genotype of the GSTP1 gene were ascertained to be genetic markers for a risk for BC. The presence of the *2C (OR = 1.69 allele of the CYP1A1 gene, the G (OR = 2.40 allele and the AG genotype (OR = 2.40 of the GSTP1 gene was associated with the invasive forms of BC. There were no substantial differences in the distribution of the frequency of genotypes of the GSTM1 gene between the samples of patients and healthy individuals.

  6. Pioglitazone has a dubious bladder cancer risk but an undoubted cardiovascular benefit.

    Science.gov (United States)

    Ryder, R E J

    2015-03-01

    On 8 April 2014, a US jury ordered Takeda and Eli Lilly to pay $9 bn in punitive damages after finding that they had concealed the cancer risks associated with pioglitazone. By contrast, on 28 August 2014, the long-awaited outcome of the 10-year Kaiser Permanente Northern California study was announced. That study was specifically designed to investigate whether patients exposed to pioglitazone were at an increased risk of bladder cancer and found no association; thus, at last, the controversial issue has been resolved. A review, in retrospect, of the story of the proposed link between pioglitazone and bladder cancer reveals flaws at every stage. In 2012, a BMJ editorial, in keeping with some other contemporary reports, stated 'it can confidently be assumed that pioglitazone increases the risk of bladder cancer'. Examination of the information which led to such a statement shows that: 1) the pre-clinical findings of bladder cancer in male rats is not indicative of human risk; 2) there is no association between bladder cancer and pioglitazone in randomized controlled trials, once cases that could not plausibly be related to treatment are removed; and 3) the observational studies that have suggested a link have over-extrapolated from the data: pioglitazone-treated patients had more risk factors for bladder cancer than those not treated with pioglitazone. Meanwhile careful study of randomized controlled trials shows evidence of cardiovascular benefit from pioglitazone in Type 2 diabetes, a condition which results, more than anything, in premature cardiovascular death and morbidity.

  7. Rosiglitazone Use and the Risk of Bladder Cancer in Patients With Type 2 Diabetes.

    Science.gov (United States)

    Han, Eugene; Jang, Suk-Yong; Kim, Gyuri; Lee, Yong-Ho; Choe, Eun Yeong; Nam, Chung Mo; Kang, Eun Seok

    2016-02-01

    Patients with diabetes have a higher incidence of bladder cancer; however, the association between thiazolidinedione use and bladder cancer risk has been controversial. We aimed to investigate whether pioglitazone or rosiglitazone use is associated with bladder cancer risk in patients with type 2 diabetes mellitus.This nationwide nested case-control study used data set obtained from the Korean National Health Insurance Service National Sample Cohort 2002 to 2013. Among the 47,738 patients with incident diabetes, 85 cases of newly diagnosed bladder cancer and 850 controls (1:10 matched by age, sex, index year, and diabetes diagnosis year) were recruited. Type 2 diabetes mellitus and bladder cancer were diagnosed using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision code.More cases of bladder cancer were diagnosed in men (81.2%), and the stratified age peaked at 70 to 79 years old. Exclusive rosiglitazone use raised the incidence of bladder cancer (odds ratio [OR] = 3.07, 95% confidence interval [CI ] = 1.48-6.37). The risk of bladder cancer started to increase after less than 3 months use (OR = 3.30, 95% CI = 1.02-10.70) and peaked at 3 to 12 months of rosiglitazone use (OR = 4.48, 95% CI = 1.51-13.31). Patients were first exposed to exclusive rosiglitazone within 1 year (OR = 11.74, 95% CI = 2.46-56.12) and those who had consistently used it for 1 year (OR = 4.48 95% CI = 1.51-13.31), had higher risks of bladder cancer compared with nonthiazolidinedione users. Neither pioglitazone use nor exclusive pioglitazone use were associated with an increased incidence of bladder cancer.Rosiglitazone use is associated with an increased risk of incident bladder cancer independent of age and sex in patients with type 2 diabetes mellitus. The highest odds of bladder cancer in rosiglitazone users was seen in those with <1 year of exposure.

  8. Risk factors for bladder cancer in a cohort exposed to aromatic amines

    Energy Technology Data Exchange (ETDEWEB)

    Schulte, P.A.; Ringen, K.; Hemstreet, G.P.; Altekruse, E.B.; Gullen, W.H.; Tillett, S.; Allsbrook, W.C. Jr.; Crosby, J.H.; Witherington, R.; Stringer, W.

    1986-11-01

    Occupational and nonoccupational risk factors for bladder cancer were analyzed in a cohort of 1385 workers with known exposure to a potent bladder carcinogen, beta-naphthylamine. Bladder cancer was approximately seven times (95% confidence interval (CI) = 3.9, 12.4) more likely in exposed rather than nonexposed individuals, yet, otherwise, the groups were generally similar in other exogenous or hereditary risk factors. A total of 13 cases of bladder cancer were identified. After the first year of a screening program involving 380 members of the cohort, 9 of the 13 cases of bladder cancer and 36 persons with atypical bladder cytology, histology, or pathology were compared with 335 noncases for distributions of different variables. Occupational variables were significant in a multivariate model that controlled for age, cigarette smoking history, and source of drinking water. The estimated odds ratio for the association for bladder cancer and the duration of employment, when controlling of these other variables, is 4.3 (95% CI = 1.8, 10.3). In addition to the occupational factors, age was significant in the multivariate analysis. Other potential risk factors, such as consumption of coffee or artificial sweeteners, use of phenacetin, or decreased use of vitamin A were not found to be significantly different in cases and noncases.

  9. Non-alcoholic beverages and risk of bladder cancer in Uruguay

    Directory of Open Access Journals (Sweden)

    Acosta Giselle

    2007-03-01

    Full Text Available Abstract Background Bladder cancer is the fourth most frequent malignancy among Uruguayan men. A previous study from Uruguay suggested a high risk of bladder cancer associated with maté drinking. We conducted an additional case-control study in order to further explore the role of non-alcoholic beverages in bladder carcinogenesis. Methods In the time period 1996–2000, 255 incident cases with transitional cell carcinoma of the bladder and 501 patients treated in the same hospitals and in the same time period were frequency matched on age, sex, and residence. Both cases and controls were face-to-face interviewed on occupation, tobacco smoking, alcohol drinking and intake of maté, coffee, tea, and soft drinks. Statistical analysis was carried out by unconditional multiple logistic regression. Results Ever maté drinking was positively associated with bladder cancer (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.2–3.9 and the risk increased for increasing duration and amount of maté drinking. Both coffee and tea were strongly associated with bladder cancer risk (OR for coffee drinking 1.6, 95% CI 1.2–2.3; OR for tea drinking 2.3, 95% CI 1.5–3.4. These results were confirmed in a separate analysis of never-smokers. Conclusion Our results suggest that drinking of maté, coffee and tea may be risk factors for bladder carcinoma in Uruguay.

  10. Defining and treating the spectrum of intermediate risk nonmuscle invasive bladder cancer

    NARCIS (Netherlands)

    Kamat, A.M.; Witjes, J.A.; Brausi, M.; Soloway, M.; Lamm, D.; Persad, R.; Buckley, R.; Bohle, A.; Colombel, M.; Palou, J.

    2014-01-01

    PURPOSE: Low, intermediate and high risk categories have been defined to help guide the treatment of patients with nonmuscle invasive bladder cancer (Ta, T1, CIS). However, while low and high risk disease has been well classified, the intermediate risk category has traditionally comprised a heteroge

  11. Prognostic value of p53 for high risk superficial bladder cancer with long-term followup.

    NARCIS (Netherlands)

    Moonen, P.M.J.; Balken-Ory, B. van; Kiemeney, L.A.L.M.; Schalken, J.A.; Witjes, J.A.

    2007-01-01

    PURPOSE: The risk of muscle invasive disease in a high risk patient with superficial bladder cancer is up to 50%. Identifying patients at risk for progression remains an unsolved problem. A suggested prognosticator is mutations in the p53 tumor suppressor gene. We determined the value of p53 mutatio

  12. A prospective study on active and environmental tobacco smoking and bladder cancer risk (The Netherlands)

    NARCIS (Netherlands)

    Zeegers, M.P.A.; Goldbohm, R.A.; Brandt, P.A. van den

    2002-01-01

    Objective: In a prospective cohort study among 120,852 adult subjects the authors investigated the associations between cigarette, cigar, pipe, environmental tobacco smoking (ETS), and bladder cancer. Methods: In 1986 all subjects completed a questionnaire on cancer risk factors. Follow-up for incid

  13. Genome-wide interaction study of smoking and bladder cancer risk

    Science.gov (United States)

    Figueroa, Jonine D.; Han, Summer S.; Garcia-Closas, Montserrat; Baris, Dalsu; Jacobs, Eric J.; Kogevinas, Manolis; Schwenn, Molly; Malats, Nuria; Johnson, Alison; Purdue, Mark P.; Caporaso, Neil; Landi, Maria Teresa; Prokunina-Olsson, Ludmila; Wang, Zhaoming; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Vineis, Paolo; Siddiq, Afshan; Cortessis, Victoria K.; Kooperberg, Charles; Cussenot, Olivier; Benhamou, Simone; Prescott, Jennifer; Porru, Stefano; Bueno-de-Mesquita, H.Bas; Trichopoulos, Dimitrios; Ljungberg, Börje; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth; Tjønneland, Anne; Brenan, Paul; Chang-Claude, Jenny; Riboli, Elio; Conti, David; Gago-Dominguez, Manuela; Stern, Mariana C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Hohensee, Chancellor; Rodabough, Rebecca; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Chen, Constance; De Vivo, Immaculata; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Lindstrom, Sara; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Karagas, Margaret R.; Schned, Alan; Armenti, Karla R.; Hosain, G.M.Monawar; Haiman, Chris A.; Fraumeni, Joseph F.; Chanock, Stephen J.; Chatterjee, Nilanjan; Rothman, Nathaniel; Silverman, Debra T.

    2014-01-01

    Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study (GWAS) of smoking and bladder cancer risk based on primary scan data from 3002 cases and 4411 controls from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P values < 5 × 10− 5 were evaluated further in an independent dataset of 2422 bladder cancer cases and 5751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial dataset and in the combined dataset, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers [combined odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.20–1.50, P value = 5.18 × 10− 7]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67–0.84, P value = 6.35 × 10− 7). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, whereas the additive interaction analysis identified more loci with associations among smokers—including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene–environment interactions for tobacco and bladder cancer. PMID:24662972

  14. Innovation in Bladder Cancer Immunotherapy.

    Science.gov (United States)

    Grossman, H Barton; Lamm, Donald L; Kamat, Ashish M; Keefe, Stephen; Taylor, John A; Ingersoll, Molly A

    2016-10-01

    Bladder cancer is understudied despite its high prevalence and its remarkable response to immunotherapy. Indeed, funding for studies to explore mechanisms of tumor immunity and novel new therapeutics is disproportionately lower for bladder cancer in comparison with malignancies of the breast, prostate, or lung. However, the recent successes of checkpoint blockade therapy suggest that new therapeutic strategies are on the horizon for bladder cancer. Here, we give a perspective into the evolution of bladder cancer therapy, focusing on strategies to treat high-risk nonmuscle invasive disease, followed by a discussion of recent advances in the treatment of muscle invasive bladder cancer and their potential applicability to lower stage disease. Finally, we explore immunotherapeutic strategies, which have been demonstrated to be successful in the treatment of other malignancies, for their potential to treat and cure patients with nonmuscle and muscle invasive bladder cancer.

  15. What Is Bladder Cancer?

    Science.gov (United States)

    ... of the bladder through a tube called the urethra . Start and spread of bladder cancer The wall of the bladder has several layers, ... called the renal pelvis ), the ureters, and the urethra. Patients with bladder cancer sometimes have other tumors in these places, so ...

  16. Personal hair dye use and the risk of bladder cancer: a case-control study from The Netherlands

    NARCIS (Netherlands)

    Ros, M.M.; Gago-Dominguez, M.; Aben, K.K.; Bueno-De-Mesquita, H.B.; Kampman, E.; Vermeulen, S.; Kiemeney, L.A.

    2012-01-01

    BACKGROUND: Several studies have suggested an increased risk of bladder cancer among hairdressers, who are occupationally exposed to hair dyes. There has also been concern about a possible increased risk of bladder cancer among users of hair dyes. However, the association between personal hair dye u

  17. Personal hair dye use and the risk of bladder cancer: a case–control study from The Netherlands

    NARCIS (Netherlands)

    Ros, M.; Gago-Dominguez, M.; Bueno de Mesquita, H.B.; Kampman, E.; Vermeulen, S.H.; Kiemeney, L.A.

    2012-01-01

    Background - Several studies have suggested an increased risk of bladder cancer among hairdressers, who are occupationally exposed to hair dyes. There has also been concern about a possible increased risk of bladder cancer among users of hair dyes. However, the association between personal hair dye

  18. Personal hair dye use and the risk of bladder cancer : a case-control study from The Netherlands

    NARCIS (Netherlands)

    Ros, Martine M.; Gago-Dominguez, Manuela; Aben, Katja K. H.; Bueno-de-Mesquita, H. Bas; Kampman, Ellen; Vermeulen, Sita H.; Kiemeney, Lambertus A.

    2012-01-01

    Several studies have suggested an increased risk of bladder cancer among hairdressers, who are occupationally exposed to hair dyes. There has also been concern about a possible increased risk of bladder cancer among users of hair dyes. However, the association between personal hair dye use and bladd

  19. Genome-wide association study identifies multiple loci associated with bladder cancer risk

    Science.gov (United States)

    Figueroa, Jonine D.; Ye, Yuanqing; Siddiq, Afshan; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Prokunina-Olsson, Ludmila; Cortessis, Victoria K.; Kooperberg, Charles; Cussenot, Olivier; Benhamou, Simone; Prescott, Jennifer; Porru, Stefano; Dinney, Colin P.; Malats, Núria; Baris, Dalsu; Purdue, Mark; Jacobs, Eric J.; Albanes, Demetrius; Wang, Zhaoming; Deng, Xiang; Chung, Charles C.; Tang, Wei; Bas Bueno-de-Mesquita, H.; Trichopoulos, Dimitrios; Ljungberg, Börje; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth; Tjønneland, Anne; Brenan, Paul; Chang-Claude, Jenny; Riboli, Elio; Conti, David; Gago-Dominguez, Manuela; Stern, Mariana C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Hohensee, Chancellor; Rodabough, Rebecca; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Chen, Constance; De Vivo, Immaculata; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Lindstrom, Sara; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Kamat, Ashish M.; Lerner, Seth P.; Barton Grossman, H.; Lin, Jie; Gu, Jian; Pu, Xia; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Kogevinas, Manolis; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Schwenn, Molly; Karagas, Margaret R.; Johnson, Alison; Schned, Alan; Armenti, Karla R.; Hosain, G.M.; Andriole, Gerald; Grubb, Robert; Black, Amanda; Ryan Diver, W.; Gapstur, Susan M.; Weinstein, Stephanie J.; Virtamo, Jarmo; Haiman, Chris A.; Landi, Maria T.; Caporaso, Neil; Fraumeni, Joseph F.; Vineis, Paolo; Wu, Xifeng; Silverman, Debra T.; Chanock, Stephen; Rothman, Nathaniel

    2014-01-01

    Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10−5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10−9) and rs907611 on 11p15.5 (P = 4.11 × 10−8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10−7) and rs4510656 on 6p22.3 (P = 6.98 × 10−7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis. PMID:24163127

  20. Red and processed meat intake and risk of bladder cancer: a meta-analysis.

    Science.gov (United States)

    Li, Fei; An, Shengli; Hou, Lina; Chen, Pengliang; Lei, Chengyong; Tan, Wanlong

    2014-01-01

    Findings from epidemiologic studies concerning red and processed meat intake and bladder cancer risk remain conflicting. Thus, we conducted this meta-analysis to examine the associations of red and processed meat intake with bladder cancer. Eligible studies published up to May 2014 were retrieved via both computer searches and review of references. Finally, we identified 14 studies on red meat (involving 9,084 cases) and 11 studies on processed meat (7,562 cases) involving up to 1,558,848 individuals. Random-effects models were used to estimate summary relative risk estimates (SRRE) based on high vs. low intake, and heterogeneity between study results was explored through stratified analyses on the basis of red/processed meat category, gender, study design and geographical region. Overall, the SRRE for all studies regarding red meat intake was 1.15 (95% CI: 0.97-1.36). Significant positive association was observed between processed meat consumption and bladder cancer (SRRE = 1.22; 95% CI: 1.04-1.43). Interestingly, increased by 25% and 33% risk of bladder cancer were observed for red meat and processed meat intake respectively in populations from the American continent. In conclusion, our fi ndings showed that there was an absence of an association between red meat intake and bladder cancer, but suggested that high consumption of processed meat probably correlated with rising risk of bladder cancer. In addition, positive relationships were observed regarding people intake of red and processed meat in the American continent. These findings need to be confirmed in future research.

  1. Risk factors for bladder cancer: challenges of conducting a literature search using PubMed.

    Science.gov (United States)

    Joshi, Ashish; Preslan, Elicia

    2011-04-01

    The objective of this study was to assess the risk factors for bladder cancer using PubMed articles from January 2000 to December 2009. The study also aimed to describe the challenges encountered in the methodology of a literature search for bladder cancer risk factors using PubMed. Twenty-six categories of risk factors for bladder cancer were identified using the National Cancer Institute Web site and the Medical Subject Headings (MeSH) Web site. A total of 1,338 PubMed searches were run using the term "urinary bladder cancer" and a risk factor term (e.g., "cigarette smoking") and were screened to identify 260 articles for final analysis. The search strategy had an overall precision of 3.42 percent, relative recall of 12.64 percent, and an F-measure of 5.39 percent. Although search terms derived from MeSH had the highest overall precision and recall, the differences did not reach significance, which indicates that for generalized, free-text searches of the PubMed database, the searchers' own terms are generally as effective as MeSH terms.

  2. Influence of metformin intake on the risk of bladder cancer in type 2 diabetes patients

    NARCIS (Netherlands)

    Goossens, Maria E; Buntinx, Frank; Zeegers, Maurice P; Driessen, J H M; De Bruin, Marie L; de Vries, Frank

    2015-01-01

    OBJECTIVE: The aim of this study is to look at the influence of metformin intake and duration, on urinary bladder cancer (UBC) risk, with sulfonylurea (SU) only users as control using a new-user design (inception cohort). METHODS: We conducted a retrospective cohort study using data from the UK Clin

  3. Food, nutrient and heterocyclic amine intake and the risk of bladder cancer.

    Science.gov (United States)

    García-Closas, Reina; García-Closas, Montserrat; Kogevinas, Manolis; Malats, Núria; Silverman, Debra; Serra, Consol; Tardón, Adonina; Carrato, Alfredo; Castaño-Vinyals, Gemma; Dosemeci, Mustafa; Moore, Lee; Rothman, Nathaniel; Sinha, Rashmi

    2007-07-01

    Fruit and vegetable intake has been linked to bladder cancer risk; however, evidence for other foods or specific dietary factors is inconclusive. The association between diet and bladder cancer risk was evaluated among 912 incident bladder cancer cases and 873 controls in Spain. Data were consistent with a reduced bladder cancer risk associated with high fruit intake; however, the association was significant only among current smokers (OR (95% CI) for 5th versus 1st quintile: 0.5 (0.3-0.9), p trend=0.009). Evaluation of food subgroups showed significant inverse associations with high intakes of berries, Liliaceae vegetables and yellow-orange vegetables. The latter association was stronger among individuals with the GSTM1 present than the null genotype (0.4 (0.2, 0.7) and 0.9 (0.6, 1.3), respectively; p for interaction=0.04). Meat or fish intake, their cooking methods or level of doneness, or heterocyclic amine intakes were not significantly associated with risk. Intake of folate, other B-vitamins (B12, B6, B2) and retinol was also associated with a reduced risk, the strongest associations being for vitamin B6 (0.6 (0.4, 0.8) p trend=0.0006) and retinol (0.6 (0.4-0.9) p trend=0.004). Our findings indicate that fruit and vegetable intake, as well as B-vitamin and retinol intake might be associated with a reduced bladder cancer risk.

  4. Pioglitazone and the risk of bladder cancer: An Indian retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Sunil Gupta

    2015-01-01

    Full Text Available Aim: To determine whether pioglitazone is associated with an increased risk of bladder cancer among Indian type 2 diabetic patients. Methods: A retrospective data analysis of 2222 type 2 diabetic patients was conducted. The study subjects were divided into two equal groups: 1111 pioglitazone users and 1111 pioglitazone non-users. The safety of pioglitazone therapy was analyzed in terms of occurrence of bladder and other types of cancers along with its efficacy in terms of glycemic control. Parameters for assessing safety were duration of disease, duration of usage and total dose of pioglitazone consumed across age groups, glycemic control, obesity and family history of any cancer. Bladder cancer prevalence was analyzed on the basis of urinary cytology, urine routine and microscopy, hematuria, urinary nuclear matrix protein 22 analysis and ultrasonography. Results: Of the 2222 cases analysed, there was no evidence of bladder cancer in any of the studied groups, (p=not significant which was also evident among 1111 patients on Pioglitazone therapy with a cumulative dose consumption of 2737 mg to 1,31,400 mg. On subgroup analysis, there was no evidence of bladder cancer amongst patients with age >60 years, duration of diabetes > 10 years and uncontrolled diabetics (HbA1c >8% with cumulative pioglitazone consumption of >28,000 mg. A significant number of patients achieved good glycemic control (HbA1c <7.5% with pioglitazone therapy. Conclusion: Pioglitazone therapy was not associated with occurrence of bladder cancer among Indian type 2 diabetic patients and demonstrated good glycemic control.

  5. Optimal Treatment for Intermediate- and High-Risk, Nonmuscle-Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    A.P.M. van der Meijden

    2006-01-01

    Full Text Available According to clinical and pathological factors the prognosis of a patient with non-muscle invasive bladder tumors can be assessed. The prognosis is determined by the likelihood of recurrence(30-70% and/or progression to muscle invasive bladder cancer(1-15%.Trans urethral resection of bladder tumors remains the initial therapy but adjuvant intravesical instillations are necessary.All patients benefit from a single immediate post operative instillation with a chemotherapeutic agent and for low risk tumors this is the optimal therapy.Patients with intermediate and high risk tumors need more intravesical chemo-or immunotherapy. Chemotherapy reduces recurrences but not progression. Intravesical immunotherapy(BCG prevents or delays progression. Patients at high risk for progression may need upfront cystectomy.

  6. Smoking, occupation, history of selected diseases and bladder cancer risk in Manisa, Turkey.

    Science.gov (United States)

    Erdurak, Koray; Dundar, Pinar E; Ozyurt, Beyhan C; Negri, Eva; La Vecchia, Carlo; Tay, Ziya

    2014-01-01

    The aim of the study was to identify and quantify the reasons for the high bladder cancer rates in Turkey. We conducted a case-control study in Manisa, Turkey, in 2011. The study included 173 patients with incident, histologically confirmed bladder cancer and 282 controls who were frequency matched by age, sex and geographic area, admitted to the main hospital of Manisa for a wide range of acute diseases. Adjusted odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were derived from multiple logistic regression models. Compared with never smokers, the OR was 2.9 (95% CI 1.5-5.4) for moderate (occupations a priori defined as being of high risk (OR=1.3), nor with farming (OR=1.2). Bladder cancer risk was directly related to the history of urinary tract infections (OR=1.9, 95% CI 1.2-3.1) but not to diabetes (OR=0.7) or kidney (OR=0.7) and prostate (OR=1.3) diseases. Tobacco is the major risk factor for bladder cancer in Manisa, being responsible for 56% of cases; urinary tract infections account for 19% of cases, whereas the role of occupational exposure is limited in this, predominantly rural, population.

  7. Strong association between long and heterogeneous telomere length in blood lymphocytes and bladder cancer risk in Egyptian.

    Science.gov (United States)

    Wang, Hongkun; Wang, Ying; Kota, Krishna K; Kallakury, Bhaskar; Mikhail, Nabiel N; Sayed, Douaa; Mokhtar, Ahmed; Maximous, Doaa; Yassin, Etemad H; Gouda, Iman; Sobitan, Adebiyi; Sun, Bing; Loffredo, Christopher A; Zheng, Yun-Ling

    2015-11-01

    Although it is widely recognized that telomere dysfunction plays an important role in cancer, the relationship between telomere function and bladder cancer risk is not well defined. In a case-control study of bladder cancer in Egypt, we examined relationships between two telomere features and bladder cancer risk. Telomere fluorescent in situ hybridization was used to measure telomere features using short-term cultured blood lymphocytes. Logistic regression was used to estimate the strength of association between telomere features and the risk of urothelial carcinoma of the bladder. High telomere length variation (TLV) across all chromosomal ends was significantly associated with an increased risk of bladder cancer [adjusted odds ratios (OR) = 2.22, 95% confidence interval (CI) = 1.48-3.35], as was long average telomere length (OR = 3.19, 95% CI = 2.07, 4.91). Further, TLV and average telomere length jointly affected bladder cancer risk: when comparing individuals with long telomere length and high TLV to those with short telomere length and low TLV, the adjusted OR was 14.68 (95% CI: 6.74-31.98). These associations were stronger among individuals who are 60 years of age or younger. In summary, long and heterogeneous telomere length in blood lymphocytes was strongly associated with an increased bladder cancer risk in Egyptian and the association was modulated by age.

  8. Treatment Option Overview (Bladder Cancer)

    Science.gov (United States)

    ... Cancer Treatment Bladder Cancer Screening Research Bladder Cancer Treatment (PDQ®)–Patient Version General Information About Bladder Cancer ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) depends on ...

  9. Large-scale evaluation of candidate genes identifies associations between VEGF polymorphisms and bladder cancer risk.

    Directory of Open Access Journals (Sweden)

    Montserrat García-Closas

    2007-02-01

    Full Text Available Common genetic variation could alter the risk for developing bladder cancer. We conducted a large-scale evaluation of single nucleotide polymorphisms (SNPs in candidate genes for cancer to identify common variants that influence bladder cancer risk. An Illumina GoldenGate assay was used to genotype 1,433 SNPs within or near 386 genes in 1,086 cases and 1,033 controls in Spain. The most significant finding was in the 5' UTR of VEGF (rs25648, p for likelihood ratio test, 2 degrees of freedom = 1 x 10(-5. To further investigate the region, we analyzed 29 additional SNPs in VEGF, selected to saturate the promoter and 5' UTR and to tag common genetic variation in this gene. Three additional SNPs in the promoter region (rs833052, rs1109324, and rs1547651 were associated with increased risk for bladder cancer: odds ratio (95% confidence interval: 2.52 (1.06-5.97, 2.74 (1.26-5.98, and 3.02 (1.36-6.63, respectively; and a polymorphism in intron 2 (rs3024994 was associated with reduced risk: 0.65 (0.46-0.91. Two of the promoter SNPs and the intron 2 SNP showed linkage disequilibrium with rs25648. Haplotype analyses revealed three blocks of linkage disequilibrium with significant associations for two blocks including the promoter and 5' UTR (global p = 0.02 and 0.009, respectively. These findings are biologically plausible since VEGF is critical in angiogenesis, which is important for tumor growth, its elevated expression in bladder tumors correlates with tumor progression, and specific 5' UTR haplotypes have been shown to influence promoter activity. Associations between bladder cancer risk and other genes in this report were not robust based on false discovery rate calculations. In conclusion, this large-scale evaluation of candidate cancer genes has identified common genetic variants in the regulatory regions of VEGF that could be associated with bladder cancer risk.

  10. Use of nonsteroidal anti-inflammatory drugs and bladder cancer risk: a meta-analysis of epidemiologic studies.

    Directory of Open Access Journals (Sweden)

    Haifeng Zhang

    Full Text Available PURPOSE: Several epidemiologic studies have evaluated the association between nonsteroidal anti-inflammatory drugs (NSAIDs and bladder cancer risk and the results were varied. Thus, we conducted a comprehensive meta-analysis of studies exclusively dedicated to the relationship between the 3 most commonly used analgesics and bladder cancer risk. METHODS: A systematic literature search up to November 2012 was performed in PubMed database for 3 categories of analgesics: acetaminophen, aspirin or non-aspirin NSAIDs. Study-specific risk estimates were pooled using a random-effects model. RESULTS: Seventeen studies (8 cohort and 9 case-control studies, involving a total of 10,618 bladder cancer cases, were contributed to the analysis. We found that acetaminophen (relative risk [RR] 1.01, 95% confidence interval [CI] 0.88-1.17 and aspirin (RR 1.02, 95% CI 0.91-1.14 were not associated with bladder cancer risk. Although non-aspirin NSAIDs was statistically significantly associated with reduced risk of bladder cancer among case-control studies (but not cohort studies, the overall risk was not statistically significant (RR 0.87, 95% CI 0.73-1.05. Furthermore, we also found that non-aspirin NSAIDs use was significantly associated with a 43% reduction in bladder cancer risk among nonsmokers (RR 0.57, 95% CI 0.43-0.76, but not among current smokers. CONCLUSION: The results of our meta-analysis suggest that there is no association between use of acetaminophen, aspirin or non-aspirin NSAIDs and bladder cancer risk. However, non-aspirin NSAIDs use might be associated with a reduction in risk of bladder cancer for nonsmokers.

  11. Elevated bladder cancer risk due to colorants--a statewide case-control study in North Rhine-Westphalia, Germany.

    Science.gov (United States)

    Golka, Klaus; Heitmann, Peter; Gieseler, Frank; Hodzic, Jasmin; Masche, Nicolas; Bolt, Hermann M; Geller, Frank

    2008-01-01

    Occupational exposure to aromatic amines is a known bladder cancer risk factor, whereas the impact of exposure to azo dyes, which may release aromatic amines in humans, is at present controversial. Therefore, the impact of occupational exposures to colorants was investigated in 156 bladder cancer cases and 336 controls in the state of North Rhine-Westphalia. All bladder cancer cases and controls (diagnosed with prostate cancer) requested after-care treatment. The subjects were investigated using a questionnaire for all occupations ever performed for more than 6 mo and for exposures to several possible occupational and nonoccupational bladder carcinogens. The relative bladder cancer risk was adjusted for age and smoking. The adjusted odds ratio (OR) for bladder cancer was elevated in 7 painters (OR 1.98, 95% CI 0.64-6.11), 4 hairdressers (OR 4.9, 95% CI 0.85-28.39), and 16 cases who reported a wood processing occupation (OR 1.19, 95% CI 0.58-2.41). Ten of these 16 cases reported chronic exposure to colorants (OR 1.84, 95% CI 0.68-4.95). The results of this epidemiological study confirm the hypothesis that individuals exposed to colorants show an elevated bladder cancer risk.

  12. Citrus fruit intake and bladder cancer risk: a meta-analysis of observational studies.

    Science.gov (United States)

    Liang, Sudong; Lv, Gaofei; Chen, Weikai; Jiang, Jianxin; Wang, Jingqun

    2014-11-01

    Epidemiological studies have investigated the association between citrus fruit and bladder cancer risk; however, the results are inconsistent. To assess these issues, we conducted a meta-analysis of currently available studies. We identified relevant articles by searching the MEDLINE and EMBASE databases. We calculated the summary relative risk (RR) with 95% confidence interval (95% CI) using a random effect model. We included eight case-control studies and six cohort studies in the meta-analysis. There was a significant inverse association between citrus fruit intake and bladder cancer risk in all pooled studies (RR: 0.85; 95% CI, 0.76-0.94) and case-control studies (RR: 0.77; 95% CI, 0.64-0.92), but not in the cohort studies (RR: 0.96; 95% CI, 0.87-1.07). Our results suggest that citrus fruit intake is related to decreased bladder cancer risk. Subsequent well-designed, large prospective studies are needed to obtain better understanding of this relationship.

  13. Genetic variants in telomere-maintenance genes and bladder cancer risk

    Institute of Scientific and Technical Information of China (English)

    Chengyuan Gu; Yao Zhu; Dingwei Ye

    2013-01-01

    Telomere maintenance genes play an important role in maintaining the integrity of the telomere structure that protects chromosome ends, and telomere dysfunction may lead to tumorigenesis. Genetic variation in telomere maintenance genes has been confirmed. Cumulative evidence shows that the dif erence of telomere length and stability among the indi-vidual depends on the genetic variants of telomere maintenance genes. Genetic variants in telomere maintenance genes may af ect telomere length and stability, thus the increased cancer risk. This review intends to summarize the association of genetic variants in telomere maintenance genes with bladder cancer risk.

  14. Fruits, vegetables, and bladder cancer risk: a systematic review and meta-analysis.

    Science.gov (United States)

    Vieira, Ana R; Vingeliene, Snieguole; Chan, Doris S M; Aune, Dagfinn; Abar, Leila; Navarro Rosenblatt, Deborah; Greenwood, Darren C; Norat, Teresa

    2015-01-01

    Smoking is estimated to cause about half of all bladder cancer cases. Case-control studies have provided evidence of an inverse association between fruit and vegetable intake and bladder cancer risk. As part of the World Cancer Research/American Institute for Cancer Research Continuous Update Project, we conducted a systematic review and meta-analysis of prospective studies to assess the dose-response relationship between fruit and vegetables and incidence and mortality of bladder cancer. We searched PubMed up to December 2013 for relevant prospective studies. We conducted highest compared with lowest meta-analyses and dose-response meta-analyses using random effects models to estimate summary relative risks (RRs) and 95% confidence intervals (CIs), and used restricted cubic splines to examine possible nonlinear associations. Fifteen prospective studies were included in the review. The summary RR for an increase of 1 serving/day (80 g) were 0.97 (95% CI: 0.95-0.99) I(2)  = 0%, eight studies for fruits and vegetables, 0.97 (95% CI: 0.94-1.00, I(2)  = 10%, 10 studies) for vegetables and 0.98 (95% CI: 0.96-1.00, I(2)  = 0%, 12 studies) for fruits. Results were similar in men and women and in current, former and nonsmokers. Amongst fruits and vegetables subgroups, for citrus fruits the summary RR for the highest compared with the lowest intake was 0.87 (95% CI: 0.76-0.99, I(2)  = 0%, eight studies) and for cruciferous vegetables there was evidence of a nonlinear relationship (P = 0.001). The current evidence from cohort studies is not consistent with a role for fruits and vegetables in preventing bladder cancer.

  15. Variety in vegetable and fruit consumption and risk of bladder cancer in the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Büchner, F.L.; Bueno de Mesquita, H.B.; Ros, M.M.; Kampman, E.; Duijnhoven, van F.J.B.

    2011-01-01

    Recent research does not show an association between fruit and vegetable consumption and bladder cancer risk. None of these studies investigated variety in fruit and vegetable consumption, which may capture different aspects of consumption. We investigated whether a varied consumption of vegetables

  16. Pioglitazone does not increase the risk of type II diabetes in patients with bladder cancer: A retrospective study.

    Science.gov (United States)

    Dong, Youhong; Wang, Anping

    2016-07-01

    The aim of the retrospective study was to analyze the effect of pioglitazone on the expression of tumor tissue inflammation factor interleukin (IL)-8, macrophage colony-stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF) of type II diabetes in bladder cancer patients. In addition, whether there was a correlation between pioglitazone and the occurrence of male bladder cancer was also investigated. In total, 42 male cases diagnosed with type II diabetes secondary to bladder cancer were selected. Forty male cases, with simplex type II diabetes but not with bladder cancer, served as the control. Tumor biopsy specimens were collected to detect the expression levels of IL-8, M-CSF and VEGF. The results showed that the expression of IL-8, M-CSF and VEGF of the simplex diabetes group was significantly lower than that of the secondary to tumor group (Ppioglitazone, duration of diabetes, average fasting blood sugar and glycated hemoglobin levels, was not statistically significant. Multivariable logistic regression analysis revealed that the expression levels of IL-8, M-CSF and VEGF were independent risk factors for the occurrence of bladder cancer (Ppioglitazone (P>0.05). In conclusion, oral pioglitazone may not increase the risk of type II diabetes patients with bladder cancer. However, the occurrence of bladder cancer be associated with the increasing expression levels of IL-8, M-CSF and VEGF.

  17. Cigarette Smoking, N-Acetyltransferase 2 Acetylation Status, and Bladder Cancer Risk

    DEFF Research Database (Denmark)

    Marcus, P.M.; Hayes, R.B.; Vineis, P.;

    2000-01-01

    Tobacco use is an established cause of bladder cancer. The ability to detoxify aromatic amines, which are present in tobacco and are potent bladder carcinogens, is compromised in persons with the N-acetyltransferase 2 slow acetylation polymorphism. The relationship of cigarette smoking with bladder...

  18. [Occupational hazards and bladder cancer].

    Science.gov (United States)

    Nizamova, R S

    1991-01-01

    Occupational exposure to health hazards was studied in 258 industrial workers who had developed cancer of the bladder against 454 matched controls. All the test subjects and controls were residents of the Tambov Province centers of chemical industry. Statistical significance (relative risk-4.7) was established for exposure to aromatic amines. For those contacting with aniline dyes the relative risk (RR) made up 2.4. The risk to develop bladder cancer in powder shops (RR-3.2) was attributed to the hazards of dyes and diphenylamine. In leather-shoe and textile industry the exposure to dyes was not safe (RR-6.1), neither was it to chemicals, oil products, pesticides, overheating (RR-3.2, 1.6, 3.2 and 2.9, respectively). It is stated that in line with a significant risk to develop bladder cancer at exposure to aromatic amines there exist a number of occupational factors contributing to this risk.

  19. Pioglitazone prescription increases risk of bladder cancer in patients with type 2 diabetes: an updated meta-analysis.

    Science.gov (United States)

    He, Shiyao; Tang, Yu-hong; Zhao, Guobin; Yang, Xiaolong; Wang, Dehou; Zhang, Ye

    2014-03-01

    Pioglitazone is widely used for glycemic control in patients with type 2 diabetes mellitus, but evidence regarding the association between pioglitazone and bladder cancer risk is confusing. A systematic search of databases was carried out, and other relevant papers were also identified. Then, the analyses were conducted according to the PRISMA and MOOSE guidelines. After quality assessment, nine datasets from 10 available studies were included on the basis of inclusion criteria. The incidence of bladder cancer among pioglitazone ever users and never users, pooled from four cohort and one randomized studies, were 84.51 and 66.68 per 100,000 person-years, respectively. Nine studies representing 2,596,856 diabetic patients were recognized as eligible for overall study; the result suggested an increased risk of bladder cancer in patients exposed to pioglitazone. A persistent significance was detected after being adjusted by age, gender, and use of other diabetes medications. Subgroup analyses indicated that the significantly increased incidence of bladder cancer was found in men, but not in women. Additionally, the analyses addressing increasing exposure to pioglitazone observed a dose-response relation between exclusive ever use of pioglitazone and bladder cancer in terms of cumulative duration of use and cumulative dosage. With some limitations, our results suggest an increased risk of bladder cancer in diabetic patients using pioglitazone, especially for men with long-term and high-dose exposure. Additional studies are needed to provide more precise evidences to support our results.

  20. Type 2 diabetes mellitus, insulin-use and risk of bladder cancer in a large cohort study.

    Science.gov (United States)

    Newton, Christina C; Gapstur, Susan M; Campbell, Peter T; Jacobs, Eric J

    2013-05-01

    Type 2 diabetes mellitus (T2DM) is associated with increased bladder cancer incidence in some, but not all, studies. Many studies had limited statistical power and few examined risk by insulin-use, duration of diabetes or cancer stage. We examined the association between T2DM and bladder cancer incidence in the Cancer Prevention Study II Nutrition Cohort, a large prospective study with information on insulin-use and duration of diabetes. Diabetes and insulin-use were ascertained from a questionnaire at study enrollment in 1992 or 1993 and updated in 1997 and every 2 years thereafter. During follow-up through 2007, 1,852 cases of incident bladder cancer were identified among 172,791 participants. Multivariable adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using extended Cox regression modeling. There were no associations of T2DM with the risk of bladder cancer overall (RR = 1.01, 95% CI: 0.87-1.17), noninvasive disease (RR = 0.93, 95% CI: 0.76-1.14) or invasive disease (RR = 1.13, 95% CI: 0.91-1.40). Compared to participants without T2DM, risk of invasive bladder cancer was higher among participants who had had T2DM for >15 years (RR = 1.63, 95% CI: 1.09-2.43) and among those using insulin (RR = 1.64, 95% CI: 1.18-2.27). These results do not support an association of T2DM with overall bladder cancer incidence, but do suggest positive associations of long-term T2DM and insulin-use or other factors correlated with severe diabetes, with invasive bladder cancer incidence.

  1. Fruit and vegetable intakes are associated with lower risk of bladder cancer among women in the Multiethnic Cohort Study.

    Science.gov (United States)

    Park, Song-Yi; Ollberding, Nicholas J; Woolcott, Christy G; Wilkens, Lynne R; Henderson, Brian E; Kolonel, Laurence N

    2013-08-01

    Fruits and vegetables have been examined for their possible effects on the risk of bladder cancer, as they contain numerous nutrients, phytochemicals, and antioxidants with potentially anticarcinogenic properties. In a prospective analysis of 185,885 older adults participating in the Multiethnic Cohort Study, we examined whether the consumption of fruits and vegetables, or of nutrients concentrated in fruits and vegetables, was associated with bladder cancer risk. Cox proportional hazards models were used to calculate HRs and 95% CIs for bladder cancer in relation to dietary intakes. A total of 581 invasive bladder cancer cases (429 men and 152 women) were diagnosed over a mean follow-up period of 12.5 y. In women, total fruits and vegetables [HR = 0.35 (95% CI: 0.22, 0.56); highest vs. lowest quartile], total vegetables [HR = 0.49 (95% CI: 0.29, 0.83)], yellow-orange vegetables [HR = 0.48 (95% CI: 0.30, 0.77)], total fruits [HR = 0.54 (95% CI: 0.34, 0.85)], and citrus fruits [HR = 0.56 (95% CI: 0.34, 0.90)] were inversely associated with the risk of invasive bladder cancer in risk factor-adjusted models. In addition, women with the highest intakes of vitamins A, C, and E; the carotenoids α-carotene, β-carotene, and β-cryptoxanthin; and folate had a lower risk of bladder cancer. For men, no associations for fruits, vegetables, or nutrients were found overall, although inverse associations were observed for vegetable intake among current smokers, and in ethnic-specific analyses, for fruit and vegetable intake among Latinos specifically. Our findings suggest that greater consumption of fruits and vegetables may lower the risk of invasive bladder cancer among women and highlight the need for specific subgroup analyses in future studies.

  2. Non-muscle invasive bladder cancer risk stratification

    Directory of Open Access Journals (Sweden)

    Sumit Isharwal

    2015-01-01

    Conclusion: EORTC and CUETO risk tables are the two best-established models to predict recurrence and progression in patients with NMIBC though they tend to overestimate risk and have poor discrimination for prognostic outcomes in external validation. Future research should focus on enhancing the predictive accuracy of risk assessment tools by incorporating additional prognostic factors such as depth of lamina propria invasion and molecular biomarkers after rigorous validation in multi-institutional cohorts.

  3. Competing Risks Data Analysis with High-dimensional Covariates:An Application in Bladder Cancer

    Institute of Scientific and Technical Information of China (English)

    Leili Tapak; Massoud Saidijam; Majid Sadeghifar; Jalal Poorolajal; Hossein Mahjub

    2015-01-01

    Analysis of microarray data is associated with the methodological problems of high dimension and small sample size. Various methods have been used for variable selection in high-dimension and small sample size cases with a single survival endpoint. However, little effort has been directed toward addressing competing risks where there is more than one failure risks. This study compared three typical variable selection techniques including Lasso, elastic net, and likelihood-based boosting for high-dimensional time-to-event data with competing risks. The per-formance of these methods was evaluated via a simulation study by analyzing a real dataset related to bladder cancer patients using time-dependent receiver operator characteristic (ROC) curve and bootstrap .632+prediction error curves. The elastic net penalization method was shown to outper-form Lasso and boosting. Based on the elastic net, 33 genes out of 1381 genes related to bladder cancer were selected. By fitting to the Fine and Gray model, eight genes were highly significant (P< 0.001). Among them, expression of RTN4, SON, IGF1R, SNRPE, PTGR1, PLEK, and ETFDH was associated with a decrease in survival time, whereas SMARCAD1 expression was associated with an increase in survival time. This study indicates that the elastic net has a higher capacity than the Lasso and boosting for the prediction of survival time in bladder cancer patients. Moreover, genes selected by all methods improved the predictive power of the model based on only clinical variables, indicating the value of information contained in the microarray features.

  4. Chemoprevention of bladder cancer.

    Science.gov (United States)

    Kamat, Ashish M; Lamm, Donald L

    2002-02-01

    micronutrients might be impossible to synthesize in the laboratory, the general population finds it easier to take vitamin supplements. Unfortunately, dietary changes such as decreasing fat and increasing fruit and vegetable intake are more difficult to initiate. There is a mistaken notion that simply because an agent is naturally occurring, it cannot be as beneficial as taking a substance synthesized in the laboratory. Even in a high-risk group such as nuclear-bomb survivors in Japan, high consumption of vegetables and fruit is protective against bladder cancer [44]. Encouraging patients to follow an essentially healthy food habit lifestyle will be a significant contribution in the fight against cancer.

  5. Red meat, dietary nitrosamines, and heme iron and risk of bladder cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

    NARCIS (Netherlands)

    Jakszyn, P.; Gonzalez, C.A.; Lujan-Barroso, L.; Ros, M.M.; Bueno-De-Mesquita, H.B.; Roswall, N.; Tjonneland, A.M.; Buchner, F.L.; Egevad, L.; Overvad, K.; Raaschou-Nielsen, O.; Clavel-Chapelon, F.; Boutron-Ruault, M.C.; Touillaud, M.S.; Chang-Claude, J.; Allen, N.E.; Kiemeney, L.A.L.M.; Key, T.J.; Kaaks, R.; Boeing, H.; Weikert, S.; Trichopoulou, A.; Oikonomou, E.; Zylis, D.; Palli, D.; Berrino, F.; Vineis, P.; Tumino, R.; Mattiello, A.; Peeters, P.H.M.; Parr, C.L.; Gram, I.T.; Skeie, G.; Sanchez, M.J.; Larranaga, N.; Ardanaz, E.; Navarro, C.; Rodriguez, L.; Ulmert, D.; Ehrnstrom, R.; Hallmans, G.; Ljungberg, B.; Roddam, A.W.; Bingham, S.A.; Khaw, K.T.; Slimani, N.; Boffetta, P.A.; Jenab, M.; Mouw, T.; Michaud, D.S.; Riboli, E.

    2011-01-01

    BACKGROUND: Previous epidemiologic studies found inconsistent results for the association between red meat intake, nitrosamines [NDMA: N-nitrosodimethylamine, and ENOC (endogenous nitroso compounds)], and the risk of bladder cancer. We investigated the association between red meat consumption, dieta

  6. Chromosomal imbalance in the progression of high-risk non-muscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Ørntoft Torben

    2009-05-01

    Full Text Available Abstract Background Non-muscle invasive bladder neoplasms with invasion of the lamina propria (stage T1 or high grade of dysplasia are at "high risk" of progression to life-threatening cancer. However, the individual course is difficult to predict. Chromosomal instability (CI is associated with high tumor stage and grade, and possibly with the risk of progression. Methods To investigate the relationship between CI and subsequent disease progression, we performed a case-control-study of 125 patients with "high-risk" non-muscle invasive bladder neoplasms, 67 with later disease progression, and 58 with no progression. Selection criteria were conservative (non-radical resections and full prospective clinical follow-up (> 5 years. We investigated primary lesions in 59, and recurrent lesions in 66 cases. We used Affymetrix GeneChip® Mapping 10 K and 50 K SNP microarrays to evaluate genome wide chromosomal imbalance (loss-of-heterozygosity and DNA copy number changes in 48 representative tumors. DNA copy number changes of 15 key instability regions were further investigated using QPCR in 101 tumors (including 25 tumors also analysed on 50 K SNP microarrays. Results Chromosomal instability did not predict any higher risk of subsequent progression. Stage T1 and high-grade tumors had generally more unstable genomes than tumors of lower stage and grade (mostly non-primary tumors following a "high-risk" tumor. However, about 25% of the "high-risk" tumors had very few alterations. This was independent of subsequent progression. Recurrent lesions represent underlying field disease. A separate analysis of these lesions did neither reflect any difference in the risk of progression. Of specific chromosomal alterations, a possible association between loss of chromosome 8p11 and the risk of progression was found. However, the predictive value was limited by the heterogeneity of the changes. Conclusion Chromosomal instability (CI was associated with "high risk

  7. Coffee, green tea, and caffeine consumption and subsequent risk of bladder cancer in relation to smoking status: a prospective study in Japan.

    Science.gov (United States)

    Kurahashi, Norie; Inoue, Manami; Iwasaki, Motoki; Sasazuki, Shizuka; Tsugane, Shoichiro

    2009-02-01

    Coffee and caffeine consumption are thought to increase the risk of bladder cancer. However, few studies have stratified this risk by smoking status, which is a potential confounder. Here, we investigated the association between coffee, green tea (another major source of caffeine), and caffeine, and bladder cancer incidence in relation to smoking status. We conducted a population-based prospective study in a cohort of Japanese, comprising a total of 49 566 men and 54 874 women aged 40–69 years who reported their coffee and green tea consumption at baseline. During follow-up from 1990 through 2005, 164 men and 42 women were newly diagnosed with bladder cancer. Cigarette smoking was associated with an increased risk of bladder cancer, with a strong dose–response relationship. Coffee was positively associated with bladder cancer risk in men, without statistical significance. When stratified by smoking status, coffee and caffeine consumption were associated with an increased risk of bladder cancer in never- or former-smoking men, with hazard ratios (95% confidence interval) in the highest categories of coffee (one or more cups per day) and caffeine consumption compared with the lowest of 2.24 (95% CI = 1.21–4.16) and 2.05 (95% CI = 1.15–3.66), respectively. In conclusion, cigarette smoking was confirmed as a risk factor for bladder cancer. Coffee and caffeine may be associated with an increased bladder cancer risk in never or former smokers among Japanese men.

  8. Basal Tumor Cell Isolation and Patient-Derived Xenograft Engraftment Identify High-Risk Clinical Bladder Cancers

    Science.gov (United States)

    Skowron, K. B.; Pitroda, S. P.; Namm, J. P.; Balogun, O.; Beckett, M. A.; Zenner, M. L.; Fayanju, O.; Huang, X.; Fernandez, C.; Zheng, W.; Qiao, G.; Chin, R.; Kron, S. J.; Khodarev, N. N.; Posner, M. C.; Steinberg, G. D.; Weichselbaum, R. R.

    2016-01-01

    Strategies to identify tumors at highest risk for treatment failure are currently under investigation for patients with bladder cancer. We demonstrate that flow cytometric detection of poorly differentiated basal tumor cells (BTCs), as defined by the co-expression of CD90, CD44 and CD49f, directly from patients with early stage tumors (T1-T2 and N0) and patient-derived xenograft (PDX) engraftment in locally advanced tumors (T3-T4 or N+) predict poor prognosis in patients with bladder cancer. Comparative transcriptomic analysis of bladder tumor cells isolated from PDXs indicates unique patterns of gene expression during bladder tumor cell differentiation. We found cell division cycle 25C (CDC25C) overexpression in poorly differentiated BTCs and determined that CDC25C expression predicts adverse survival independent of standard clinical and pathologic features in bladder cancer patients. Taken together, our findings support the utility of BTCs and bladder cancer PDX models in the discovery of novel molecular targets and predictive biomarkers for personalizing oncology care for patients. PMID:27775025

  9. Application of multi-SNP approaches Bayesian LASSO and AUC-RF to detect main effects of inflammatory-gene variants associated with bladder cancer risk.

    Directory of Open Access Journals (Sweden)

    Evangelina López de Maturana

    Full Text Available The relationship between inflammation and cancer is well established in several tumor types, including bladder cancer. We performed an association study between 886 inflammatory-gene variants and bladder cancer risk in 1,047 cases and 988 controls from the Spanish Bladder Cancer (SBC/EPICURO Study. A preliminary exploration with the widely used univariate logistic regression approach did not identify any significant SNP after correcting for multiple testing. We further applied two more comprehensive methods to capture the complexity of bladder cancer genetic susceptibility: Bayesian Threshold LASSO (BTL, a regularized regression method, and AUC-Random Forest, a machine-learning algorithm. Both approaches explore the joint effect of markers. BTL analysis identified a signature of 37 SNPs in 34 genes showing an association with bladder cancer. AUC-RF detected an optimal predictive subset of 56 SNPs. 13 SNPs were identified by both methods in the total population. Using resources from the Texas Bladder Cancer study we were able to replicate 30% of the SNPs assessed. The associations between inflammatory SNPs and bladder cancer were reexamined among non-smokers to eliminate the effect of tobacco, one of the strongest and most prevalent environmental risk factor for this tumor. A 9 SNP-signature was detected by BTL. Here we report, for the first time, a set of SNP in inflammatory genes jointly associated with bladder cancer risk. These results highlight the importance of the complex structure of genetic susceptibility associated with cancer risk.

  10. Influence of metformin intake on the risk of bladder cancer in type 2 diabetes patients

    DEFF Research Database (Denmark)

    Goossens, Maria E; Buntinx, Frank; Zeegers, Maurice P;

    2015-01-01

    AIM: The aim of this study was to look at the influence of metformin intake and duration, on urinary bladder cancer (UBC) risk, with sulfonylurea (SU) only users as control using a new user design (inception cohort). METHODS: We conducted a retrospective cohort study using data from the UK Clinical...... Practice Research Datalink (CPRD) including all patients with at least one prescription of oral anti-diabetic drugs (ADD) and/or insulin. The risk of UBC in different groups of ADD users (metformin alone (one), metformin in combination (two) with other ADD medication (glinides, glitazones, DPP-4-inhibitors......, SUs, insulin or more than one combination), all metformin users (1 + 2) was compared with SU only users using Cox proportional hazards models. The estimates were adjusted for age, gender, smoking status, BMI and diabetes duration. RESULTS: The inception cohort included 165,398 participants of whom 132...

  11. No evidence of correlation between p53 codon 72 polymorphism and risk of bladder cancer in Moroccan patients

    Directory of Open Access Journals (Sweden)

    Noâma Berrada

    2013-01-01

    Full Text Available Background: The p53 codon 72 polymorphism has been investigated extensively for its association with various cancers around the world. Several studies have investigated the association between p53 polymorphism at codon 72 and risk of developing bladder cancer, but the results are still controversial. Aim: The aim of our study was to evaluate the association between the p53 polymorphism and the bladder cancer risk among Moroccan patients. Materials and Methods: This study was carried out on fresh biopsies from 41 patients with bladder cancer confirmed and 38 blood samples from control donors. Deoxyribonucleic acid was genotyped by "Allele-specific polymerase chain reaction" using specific primers to each polymorphic variant. Results: Frequencies of Arg/Arg, Arg/Pro and Pro/Pro genotypes among cases were 17%, 66%, and 17%, while in controls the frequencies of Arg/Arg, Arg/Pro and Pro/Pro were 15.8%, 63.2%, and 21%, respectively. The difference between cases and controls was not statistically significant. An increased risk of bladder cancer development was not clearly related to any polymorphic variant of the p53 Arg72Pro in our study group from Moroccan population. Moreover, the frequency of the Arg allele was higher (71.45% than the Pro allele (28.55% in high stage of bladder tumors, but this difference was statistically not significant. Conclusion: This study suggests that Arg allele could be more involved in developing bladder tumor in Moroccan population than the Pro allele. Therefore, enlarging the sampling will be necessary to confirm this association in Moroccan population.

  12. Polymorphic enzymes, urinary bladder cancer risk, and structural change in the local industry.

    Science.gov (United States)

    Ovsiannikov, Daniel; Selinski, Silvia; Lehmann, Marie-Louise; Blaszkewicz, Meinolf; Moormann, Oliver; Haenel, Matthias W; Hengstler, Jan G; Golka, Klaus

    2012-01-01

    In the 1990s, an uncommonly high percentage of glutathione S-transferase M1 (GSTM1) negative bladder cancer cases (70%) was reported in the greater Dortmund area. The question arose as to whether this uncommonly high percentage of GSTM1 negative bladder cancer cases was due to environmental and/or occupational exposure decades ago. Thus, 15 years later, another study on bladder cancer was performed in the same area after the coal, iron, and steel industries had finally closed in the 1990s. In total 196 bladder cancer patients from the St.-Josefs-Hospital Dortmund-Hörde and 235 controls with benign urological diseases were assessed by questionnaire and genotyped for GSTM1, glutathione S-transferase T1 (GSTT1), and the N-acetyltransferase 2 (NAT2) tag SNP rs1495741. The frequency of the GSTM1 negative genotype was 52% in bladder cancer cases and thus lower compared to a previous study performed from 1992 to 1995 in the same area (70%). NAT2 genotypes were distributed equally among cases and controls (63% slow acetylators). Fewer GSTT1 negative genotypes were present in cases (17%) than in controls (20%).

  13. Reproductive factors and menopausal hormone therapy and bladder cancer risk in the NIH-AARP Diet and Health Study.

    Science.gov (United States)

    Daugherty, Sarah E; Lacey, James V; Pfeiffer, Ruth M; Park, Yikyung; Hoover, Robert N; Silverman, Debra T

    2013-07-15

    The incidence of bladder cancer among women is at least one-third to one-fourth that observed among men in many countries. Even after accounting for known risk factors, the reason for this gender disparity remains unexplained. We conducted a comprehensive evaluation of reproductive factors and exogenous hormone use with a primary focus on menopausal hormone therapy use and risk of bladder cancer in women in the NIH-AARP Diet and Health Study. Reproductive and hormonal factors were ascertained on the baseline questionnaire in 1995-1996 among 201,492 females who were followed until December 31, 2006. During follow-up, 651 cases of bladder cancer were diagnosed. A subset of women provided detailed information on use of MHT in a second questionnaire in 1996-1997. In this analysis, 127,361 females were followed through June 30, 2002 and 198 incident bladder cancer cases were identified. Cox proportional hazard models, adjusted for smoking status, cigarettes per day and body mass index using age as the time metric, were used to obtain hazard ratios (HRs). A reduced risk was observed among parous women (HR=0.76; 95% CI 0.62-0.93) and women who reported late age at menarche (≥15 years) (HR=0.57; 95% CI 0.39-0.84). Women who reported ever using estrogen and progestin therapy had a decreased risk (HR=0.53; 95% CI: 0.34-0.83) compared with women who did not report MHT use. No association was observed for estrogen only users (HR=0.82; 95% CI: 0.58-1.15). Our results suggest a putative role for sex hormones in the etiology of bladder cancer among women.

  14. Fruit and vegetable consumption and risk of bladder cancer: an updated meta-analysis of observational studies.

    Science.gov (United States)

    Liu, Huan; Wang, Xing-Chun; Hu, Guang-Hui; Guo, Zhui-Feng; Lai, Peng; Xu, Liang; Huang, Tian-Bao; Xu, Yun-Fei

    2015-11-01

    This meta-analysis was conducted to assess the association between fruit and vegetable intake and bladder cancer risk. Eligible studies published up to August 2014 were retrieved both through a computer search of PubMed, Embase and the Cochrane library and through a manual review of references. The summary relative risks with 95% confidence intervals (CIs) for the highest versus the lowest intakes of fruits and vegetables were calculated with random-effects models. Heterogeneity and publication bias were also evaluated. Potential sources of heterogeneity were detected with metaregression. Subgroup analyses and sensitivity analyses were also performed. A total of 27 studies (12 cohort and 15 case-control studies) were included in this meta-analysis. The summary relative risks for the highest versus lowest were 0.84 (95% CI: 0.72-0.96) for vegetable intake and 0.81 (95% CI: 0.73-0.89) for fruit intake. The dose-response analysis showed that the risk of bladder cancer decreased by 8% (relative risk=0.92; 95% CI: 0.87-0.97) and 9% (relative risk=0.91; 95% CI: 0.83-0.99) for every 200 g/day increment in vegetable and fruit consumption, respectively. Sensitivity analysis confirmed the stability of the results. Our findings suggest that intake of vegetables and fruits may significantly reduce the risk of bladder cancer. Further well-designed prospective studies are warranted to confirm these findings.

  15. Outcomes of BCG Induction in High-Risk Non-Muscle-Invasive Bladder Cancer Patients (NMIBC): A Retrospective Cohort Study

    Science.gov (United States)

    Ghauri, Rashid; Ahmed, Monis J; Shah, Muhammad F; Nasir, Irfan ul Islam; Siddiqui, Jasim; Ahmed, Irfan; Mir, Khurram

    2017-01-01

    Non-muscle-invasive bladder cancer (NMIBC) is categorized into high-risk and low-risk groups. Although, bacillus Calmette-Guerin (BCG) is the recommended adjuvant therapy of high-risk bladder tumor, optimal schedule (induction versus maintenance) of this therapy is a subject of debate. The objective was to evaluate outcomes of induction BCG in high-risk NMIBC patients at Shaukat Khanum Memorial Cancer Hospital & Research Centre, Pakistan and retrospective cohort study conducted in the department of urology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Pakistan. Three-year disease-free survival and progression-free survival was the main outcome measure. Data of 68 high-risk (Ta and T1 with G3 or high-grade subtype) bladder cancer patients who underwent transurethral resection followed by six-weekly intravesical BCG instillation was included in the study. Recurrence was described as biopsy-proven bladder cancer; whereas the presence of muscle invasion was considered as progression. Disease-free survival and progression-free survival were defined as time intervals elapsed between the starting date of BCG instillation and recurrence or progression, respectively. Kaplan-Meier curve was employed to estimate the three-year study end-points. Disease-free survival at three years was observed to be 66.2% and progression-free survival at 86.8%. The use of induction BCG alone for high-risk patients of NMIBC is a viable option both in terms of effective disease-free and progression-free survival rates. PMID:28168135

  16. Genetics Home Reference: bladder cancer

    Science.gov (United States)

    ... Cancer Survivorship ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) BLADDER CANCER Sources for This Page American Cancer Society: What Are the Key Statistics for Bladder Cancer? Bryan RT, Hussain SA, James ...

  17. Rs710521[A] on chromosome 3q28 close to TP63 is associated with increased urinary bladder cancer risk.

    Science.gov (United States)

    Lehmann, Marie-Louise; Selinski, Silvia; Blaszkewicz, Meinolf; Orlich, Michael; Ovsiannikov, Daniel; Moormann, Oliver; Guballa, Christoph; Kress, Alexander; Truss, Michael C; Gerullis, Holger; Otto, Thomas; Barski, Dimitri; Niegisch, Günter; Albers, Peter; Frees, Sebastian; Brenner, Walburgis; Thüroff, Joachim W; Angeli-Greaves, Miriam; Seidel, Thilo; Roth, Gerhard; Dietrich, Holger; Ebbinghaus, Rainer; Prager, Hans M; Bolt, Hermann M; Falkenstein, Michael; Zimmermann, Anna; Klein, Torsten; Reckwitz, Thomas; Roemer, Hermann C; Löhlein, Dietrich; Weistenhöfer, Wobbeke; Schöps, Wolfgang; Beg, Anwer E; Aslam, Muhammad; Bánfi, Gergely; Romics, Imre; Ickstadt, Katja; Schwender, Holger; Winterpacht, Andreas; Hengstler, Jan G; Golka, Klaus

    2010-12-01

    Single nucleotide polymorphism (SNP) rs710521[A], located near TP63 on chromosome 3q28, was identified to be significantly associated with increased bladder cancer risk. To investigate the association of rs710521[A] and bladder cancer by new data and by meta-analysis including all published data, rs710521 was studied in 1,425 bladder cancer cases and 1,740 controls that had not been included in previous studies. Blood samples were collected from 1995 to 2010 in Germany (n = 948/1,258), Hungary (n = 262/65), Venezuela (n = 112/190) and Pakistan (n = 103/227) supplemented by a meta-analysis of 5,695 cases and 40,187 controls. Detection of a A/G substitution (rs710521) on chromosome 3q28, position 191128627 was done via fast real-time polymerase chain reaction (rt-PCR). Rs710521[A] is associated with increased risk in the unadjusted analysis (OR = 1.21; 95% Cl = 1.04-1.40; P = 0.011) and in the recessive model adjusted for age, gender, smoking habits and ethnicity (OR = 1.23; 95% Cl = 1.05-1.44; P = 0.010). No difference between individuals occupationally exposed versus not occupationally exposed to urinary bladder carcinogens was observed concerning the relevance of rs710521[A]. Similarly, rs710521[A] did not confer different susceptibility in smokers and non-smokers. Performing a meta-analysis of 5,695 cases and 40,187 controls including all published studies on rs710521, a convincing association with bladder cancer risk was obtained (OR = 1.18; 95% Cl = 1.12-1.25; P < 0.0001). However, the odds ratio is relatively small.

  18. Bladder cancer risk associated with genotypic polymorphism of the matrix metalloproteinase-1 and 7 in North Indian population.

    Science.gov (United States)

    Srivastava, Priyanka; Gangwar, Ruchika; Kapoor, Rakesh; Mittal, Rama D

    2010-01-01

    Matrix metalloproteinases (MMPs) contribute to tumor invasion and microenvironment, hence are associated with bladder cancer risk. We therefore, tested whether polymorphisms in MMP genes modify the risk of bladder cancer (BC) and whether smoke exposure modifies this risk. Genotyping was performed in 200 BC patients and 200 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). MMP1-1607 2G/2G and MMP7-181 GG genotype were associated with increased risk of BC (p BCG) treated non muscle invasive BC (NMIBC) patients (log rank p, 0.030). Our data suggested that MMP1-1607 2G and MMP7-181 G allele were associated with high risk of BC, which was quite evident amongst smokers too. BCG treated NMIBC patients reflected protective effect for 2G allele carrier (1G/2G + 2G/2G) of MMP1-1607. This study provided new support for the association of MMP1-1607 and MMP7-181 in bladder cancer development, the tumorigenic effect of which was observed to be more enhanced in case of tobacco exposure.

  19. Risk of urinary bladder cancer: a case-control analysis of industry and occupation

    Directory of Open Access Journals (Sweden)

    Wu Xifeng

    2009-12-01

    Full Text Available Abstract Background Uncertainty remains about urinary bladder cancer (UBC risk for many occupations. Here, we investigate the association between occupation, industry and UBC. Methods Lifetime occupational history was collected by in-person interview for 604 newly diagnosed UBC patients and 604 cancer-free controls. Each job title was assigned a two-digit industry code and a three-digit occupation code. Odds ratios (ORs for UBC associated with ever being employed in an industry or occupation were calculated by unconditional logistic regression adjusting for age, gender and smoking status. We also examined UBC risk by duration of employment (>0 to Results Significantly increased risk of UBC was observed among waiters and bartenders (OR 2.87; 95% CI 1.05 to 7.72 and occupations related to medicine and health (OR 2.17; 95% CI 1.21 to 3.92, agricultural production, livestock and animal specialties (OR 1.90; 95% CI 1.03 to 3.49, electrical assembly, installation and repair (OR 1.69; 95% CI 1.07 to 2.65, communications (OR 1.74; 95% CI 1.00 to 3.01, and health services (OR 1.58; 95% CI 1.02 to 2.44. For these occupations we also observed a significant excess risk of UBC for long-term work (i.e. ≥10 years, with the exception of waiters and bartenders. Employment for 10 years or more was associated with increased risk of UBC in general farmers (OR 9.58; 95% CI 2.18 to 42.05, agricultural production of crops (OR 3.36; 95% CI 1.10 to 10.27, occupations related to bench working (OR 4.76; 95% CI 1.74 to 13.01, agricultural, fishery, forestry & related (OR 4.58; 95% CI 1.97 to 10.65, transportation equipment (OR 2.68; 95% CI 1.03 to 6.97, and structural work (OR 1.85; 95% CI 1.16 to 2.95. Conclusions This study provides evidence of increased risk of UBC for occupations that were previously reported as at-risk. Workers in several occupation and industry groups have a significantly higher risk of UBC, particularly when duration of employment is 10 years or

  20. Molecular Diagnosis in Bladder Cancer

    NARCIS (Netherlands)

    T.C.M. Zuiverloon (Tahlita)

    2013-01-01

    textabstractEpidemiologyBladder cancer (BC) is the most prevalent type of urothelial cancer and is associated with thehighest costs of all cancer types due to intensive patient surveillance. Because bladder tumorsfrequently recur, patients need to be monitored extensively [1-4]. Incidence increases

  1. Circulating tumor cells detection has independent prognostic impact in high-risk non-muscle invasive bladder cancer.

    Science.gov (United States)

    Gazzaniga, Paola; de Berardinis, Ettore; Raimondi, Cristina; Gradilone, Angela; Busetto, Gian Maria; De Falco, Elena; Nicolazzo, Chiara; Giovannone, Riccardo; Gentile, Vincenzo; Cortesi, Enrico; Pantel, Klaus

    2014-10-15

    High-risk non-muscle invasive bladder cancer (NMIBC) progresses to metastatic disease in 10-15% of cases, suggesting that micrometastases may be present at first diagnosis. The prediction of risks of progression relies upon EORTC scoring systems, based on clinical and pathological parameters, which do not accurately identify which patients will progress. Aim of the study was to investigate whether the presence of CTC may improve prognostication in a large population of patients with Stage I bladder cancer who were all candidate to conservative surgery. A prospective single center trial was designed to correlate the presence of CTC to local recurrence and progression of disease in high-risk T1G3 bladder cancer. One hundred two patients were found eligible, all candidate to transurethral resection of the tumor followed by endovesical adjuvant immunotherapy with BCG. Median follow-up was 24.3 months (minimum-maximum: 4-36). The FDA-approved CellSearch System was used to enumerate CTC. Kaplan-Meier methods, log-rank test and multivariable Cox proportional hazard analysis was applied to establish the association of circulating tumor cells with time to first recurrence (TFR) and progression-free survival. CTC were detected in 20% of patients and predicted both decreased TFR (log-rank p < 0.001; multivariable adjusted hazard ratio [HR] 2.92 [95% confidence interval: 1.38-6.18], p = 0.005), and time to progression (log-rank p < 0.001; HR 7.17 [1.89-27.21], p = 0.004). The present findings provide evidence that CTC analyses can identify patients with Stage I bladder cancer who have already a systemic disease at diagnosis and might, therefore, potentially benefit from systemic treatment.

  2. Bladder cancer; Cancer de la Vessie

    Energy Technology Data Exchange (ETDEWEB)

    Pointreau, Y. [Service de radiotherapie, centre regional universitaire de cancerologie Henry-S.-Kaplan CHU de Tours, Hpital Bretonneau, 37 - Tours (France); Universite Francois-Rabelais de Tours, GICC, 37 - Tours (France); CNRS, UMR 6239 -Genetique, Immunotherapie, Chimie et Cancer-, 37 - Tours (France); CHRU de Tours, laboratoire de pharmacologie-toxicologie, 37 - Tours (France); Denis, F. [Centre Jean-Bernard, 72 - Le Mans (France); Klotz, S.; Durdux, C. [Service d' oncologie-radiotherapie, hopital europeen Georges-Pompidou, 75 - Paris (France); Denis, F. [Centre Jean-Bernard, 72 - Le Mans (France)

    2010-07-01

    Bladder cancer is an urologic common tumor after prostate carcinoma. Radical treatment of localized invasive tumor is based on cystectomy. Surgical mutilation could be important when Bricker's urinary derivation is performed. Moreover, delayed metastasis frequently appeared in spite of radical surgery. Thus, chemoradiotherapy is a valid alternative treatment to cystectomy for selected patients. Cisplatin or derivatives are usually concurrently administered to radiation therapy up to 60 - 65 Gy. Patients undergo control cystoscopy at mid-time of treatment in order to select responders from non responders. For majority of cases, the empty bladder should be entirely treated with added margins (about 20 mm) to build the PTV. Control assessment could be improved by echography, cone beam imaging as well as bladder fiduciaries implantation before treatment. From a case report, this review summarizes the technical aspects of radiation therapy (GTV, CTV and PTV, organs at risk, planning) and main acute and late related toxicities. (authors)

  3. Emerging Immunotargets in Bladder Cancer.

    Science.gov (United States)

    Massari, Francesco; Ciccarese, Chiara; Vau, Nuno; Santoni, Matteo; Montironi, Rodolfo; Cheng, Liang; Marques, Rita C; Scarpelli, Marina; Fonseca, Jorge; Matrana, Marc R; Holger, Moch; Cascinu, Stefano; Tortora, Giampaolo; Lopez-Beltran, Antonio

    2016-01-01

    Bladder cancer treatment, namely systemic therapy, was dominated in the last three decades due to the absence of newer therapeutic options other than chemotherapy regimens. Chemotherapy, by itself, both in first and second-line seems to have achieved the modest plateau of its possibilities at the cost of non-negligible toxicity. Targeted therapies, which changed the therapy of many different tumors, seem rather ineffective in bladder cancer. More recently, a new generation of Immunotherapy based regimens represent the most promising avenue for the future systemic treatment of bladder cancer. Checkpoint inhibition, namely PD1/PD-L1 pathway inhibition, showed impressive results in many other tumor types and are expected to become a major player in the treatment of bladder cancer. Other immunotherapy strategies such as fusion proteins represent distant, although promising, options. A brief overview of the current status of bladder cancer immunotherapy is presented.

  4. Drugs Approved for Bladder Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bladder cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  5. Methylenetetrahydrofolate Reductase Polymorphisms at Familial Bladder Cancer: Case Report

    Directory of Open Access Journals (Sweden)

    Gulay Ceylan

    2016-02-01

    Full Text Available Bladder cancer is the seventh most common cancer in men in the world, it is the second most seen cancer after lung cancer and the first in urogenital tumours in Turkey. Many molecular epidemiologic studies have been reported to investigate the associations between the MTHFR C677T and A1298C polymorphisms and bladder cancer risk. In this report, a family with transitional bladder cancer have also MTHFR A1298C heterozygosity which supports the association between MTHFR variants and bladder cancer. This %uFB01nding should be further validated by prospective and larger studies with more diverse ethnic groups.

  6. Association between MDM2 SNP309 T>G polymorphism and the risk of bladder cancer: new data in a Chinese population and an updated meta-analysis

    Directory of Open Access Journals (Sweden)

    Xie LG

    2015-12-01

    Full Text Available Linguo Xie,1,2,* Yan Sun,2,* Tao Chen,1,2,* Dawei Tian,1,2 Yujuan Li,3 Yu Zhang,1,2 Na Ding,2 Zhonghua Shen,1,2 Hao Xu,1,2 Xuewu Nian,4 Nan Sha,1,2 Ruifa Han,1,2 Hailong Hu,1,2 Changli Wu1,2 Objective: Human murine double minute 2 protein (MDM2 is mainly a negative regulator of p53 tumor suppressor pathway. We aimed to investigate the association between MDM2 SNP309 polymorphism and bladder cancer risk. Methods: A total of 535 bladder cancer patients and 649 health controls were recruited for our study. MDM2 SNP309 T>G polymorphism was genotyped by polymerase chain reaction-ligase detection reaction method. Logistic regression was used to analyze the relationship between the genotype and susceptibility of bladder cancer. Kaplan–Meier estimates and log-rank test were obtained to analyze the association between the genotype and risk of recrudesce in nonmuscle-invasive bladder cancer patients. A multivariable Cox proportional hazards model was fitted to identify independent prognostic factors. To further investigate the association, we conducted a meta-analysis including six studies. Results: The frequency of the MDM2 SNP309 T>G polymorphism showed no significant difference between cases and controls (all P>0.05. In the stratification analysis, the results showed that G allele carriers were prone to have a significant decrease in risk of low-grade bladder cancer (adjusted odds ratio: 0.613, 95% confidence interval: 0.427–0.881, and G variant was associated with a significantly reduced risk of recurrence in nonmuscle-invasive bladder cancer patients with or without chemotherapy (P<0.05. The results of the meta-analysis showed that G allele and GG genotype of MDM2 SNP309 polymorphism were significantly associated with increased risk of bladder cancer in Caucasians (both P<0.05, and no association was observed in total populations and Asians (P>0.05. Conclusion: MDM2 SNP309 T>G polymorphism has no influence on bladder cancer risk in Asians, but

  7. TSP-1-1223 A/G Polymorphism as a Potential Predictor of the Recurrence Risk of Bladder Cancer in a Chinese Population

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    Xiao Yang

    2013-01-01

    Full Text Available Backgrounds. TSP-1 is a glycoprotein that functions in the biology of bladder cancer. We investigated the relationship between the distribution of TSP-1-1223 A/G polymorphism (rs2169830 and the clinical characteristics of bladder cancer. Materials and Methods. TaqMan assay was performed to determine the genotype of 609 cases and 670 control subjects in a Chinese population. Logistic regression was used to assess the association between the polymorphism and the risk of bladder cancer. Quantitative real-time polymerase chain reaction was performed to determine TSP-1 mRNA expression. Survival curves were generated using the Kaplan-Meier method. Results. No significant differences were detected in the genotype frequencies of healthy control subjects and patients with bladder cancer. By contrast, the time until the first recurrence differed significantly between genotypes (P=0.017. The expression of TSP-1 mRNA in bladder cancer tissues was lower in patients with an AG genotype than in those with an AA genotype. The lowest expression was observed in patients with a GG genotype. Conclusions. In conclusion, TSP-1-1223 A/G polymorphism may contribute to the recurrence of bladder cancer in Chinese population.

  8. Bladder cancer documentation of causes: multilingual questionnaire, 'bladder cancer doc'.

    Science.gov (United States)

    Golka, Klaus; Abreu-Villaca, Yael; Anbari Attar, Rowshanak; Angeli-Greaves, Miriam; Aslam, Muhammad; Basaran, Nursen; Belik, Rouslana; Butryee, Chaniphun; Dalpiaz, Orietta; Dzhusupov, Keneshbek; Ecke, Thorsten H; Galambos, Henrieta; Galambos, Henrieta; Gerilovica, Helena; Gerullis, Holger; Gonzalez, Patricia Casares; Goossens, Maria E; Gorgishvili-Hermes, Lela; Heyns, Chris F; Hodzic, Jasmin; Ikoma, Fumihiko; Jichlinski, Patrice; Kang, Boo-Hyon; Kiesswetter, Ernst; Krishnamurthi, Kannan; Lehmann, Marie-Louise; Martinova, Irina; Mittal, Rama Devi; Ravichandran, Beerappa; Romics, Imre; Roy, Bidyut; Rungkat-Zakaria, Fransiska; Rydzynski, Konrad; Scutaru, Cristian; Shen, Jianhua; Soufi, Maria; Toguzbaeva, Karlygash; Vu Duc, Trinh; Widera, Agata; Wishahi, Mohamed; Hengstler, Jan G

    2012-06-01

    There is a considerable discrepancy between the number of identified occupational-related bladder cancer cases and the estimated numbers particularly in emerging nations or less developed countries where suitable approaches are less or even not known. Thus, within a project of the World Health Organisation Collaborating Centres in Occupational Health, a questionnaire of the Dortmund group, applied in different studies, was translated into more than 30 languages (Afrikaans, Arabic, Bengali, Chinese, Czech, Dutch, English, Finnish, French, Georgian, German, Greek, Hindi, Hungarian, Indonesian, Italian, Japanese, Kannada, Kazakh, Kirghiz, Korean, Latvian, Malay, Persian (Farsi), Polish, Portuguese, Portuguese/Brazilian, Romanian, Russian, Serbo-Croatian, Slovak, Spanish, Spanish/Mexican, Tamil, Telugu, Thai, Turkish, Urdu, Vietnamese). The bipartite questionnaire asks for relevant medical information in the physician's part and for the occupational history since leaving school in the patient's part. Furthermore, this questionnaire is asking for intensity and frequency of certain occupational and non-occupational risk factors. The literature regarding occupations like painter, hairdresser or miner and exposures like carcinogenic aromatic amines, azo dyes, or combustion products is highlighted. The questionnaire is available on www.ifado.de/BladderCancerDoc.

  9. MOLECULAR PROGNOSTIC MARKERS OF URINE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    V. N. Pavlov

    2012-01-01

    Full Text Available Bladder cancer (BC remains a current problem in oncourology. Despite that bladder cancer risk factors have been studied and described in the literature, new molecular and genetic mechanisms have been identified that predisposes to the disease development. There are numerous cellular processes involve in BC pathogenesis. The less-aggressive, non-invasive slow progressing bladder cancer types are defined by Ras-MAPK system activation. Tumors that are more aggressive and have low cancer-specific survival rate are characterized by changes in retinoblastoma genes and p53. Attempts are made to develop prognostic tests to predict tumor behavior, targeted treatment. perspectively, BC patients will be treated using molecular genetic markers allowing the accurate prediction of the patient’s tumor behavior and fitting the treatment tactics on the individual basis.

  10. Risk of bladder cancer among patients with diabetes treated with a 15 mg pioglitazone dose in Korea: a multi-center retrospective cohort study.

    Science.gov (United States)

    Jin, Sang-Man; Song, Sun Ok; Jung, Chang Hee; Chang, Jin-Sun; Suh, Sunghwan; Kang, Seung Min; Jung, Inkyung; Park, Cheol-Young; Kim, Jae Hyeon; Cho, Jae Hyoung; Lee, Byung-Wan

    2014-02-01

    It has not yet been determined whether chronic exposure to relatively low doses of pioglitazone increases risk of bladder cancer. We aimed to assess the risk of bladder cancer associated with pioglitazone in Korean patients. This was a retrospective cohort study of diabetic patients who had ≥ 2 clinic visits between November 2005 and June 2011 at one of four tertiary referral hospitals in Korea. A prevalent case-control analysis nested within the cohort was conducted to further adjust confounders. A total of 101,953 control patients and 11,240 pioglitazone-treated patients were included, in which there were 237 and 30 cases of incidental bladder cancer (64.9 and 54.9 per 100,000 person-years; age, sex-adjusted HR 1.135, 95% confidence interval [CI] 0.769-1.677), respectively. In the prevalent case-control analysis nested within the cohort, use of pioglitazone for a duration of > 6 months, but not ever use of pioglitazone, was associated with an increased rate of bladder cancer as compared to never use of pioglitazone. In conclusion, we failed to exclude the possible association between use of pioglitazone for a duration of > 6 months and bladder cancer.

  11. High-Risk Non-Muscle-Invasive Bladder Cancer-Therapy Options During Intravesical BCG Shortage.

    Science.gov (United States)

    Veeratterapillay, Rajan; Heer, Rakesh; Johnson, Mark I; Persad, Raj; Bach, Christian

    2016-09-01

    Bladder cancer is the second commonest urinary tract malignancy with 70-80 % being non-muscle invasive (NMIBC) at diagnosis. Patients with high-risk NMIBC (T1/Tis, with high grade/G3, or CIS) represent a challenging group as they are at greater risk of recurrence and progression. Intravesical Bacilli Calmette-Guerin (BCG) is commonly used as first line therapy in this patient group but there is a current worldwide shortage. BCG has been shown to reduce recurrence in high-risk NMIBC and is more effective that other intravesical agents including mitomycin C, epirubicin, interferon-alpha and gemcitabine. Primary cystectomy offers a high change of cure in this cohort (80-90 %) and is a more radical treatment option which patients need to be counselled carefully about. Bladder thermotherapy and electromotive drug administration with mitomycin C are alternative therapies with promising short-term results although long-term follow-up data are lacking.

  12. An association between hOGG1 Ser326Cys polymorphism and the risk of bladder cancer in non-smokers: a meta-analysis

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    Ji Changwei

    2012-08-01

    Full Text Available Abstract Background Bladder cancer results from complex interactions between many genetic and environment factors. The polymorphism Ser326Cys in hOGG1 gene has been reported to be associated with bladder cancer in some studies, though the results remain inconclusive. To explore this relationship of hOGG1 polymorphism and the susceptibility for bladder cancer and the impact of smoking exposures, a cumulative meta-analysis was performed in this study. Methods We extracted the data from the Pubmed database up to January 9, 2012 using the search phrases “hOGG1, Ser326Cys polymorphism and bladder cancer”. Seven case–control studies were identified, including 2474 patients and 2408 controls. Four of them provided the analysis of smoking effects, with 1372 smokers and 947 non-smokers. The odds ratios (ORs and associated 95 % confidence intervals (CIs were calculated using fixed- or random- effects models. Results Regarding the overall association between the hOGG1 326Cys allele and bladder cancer risk, the meta-analysis did not reveal a significant effect in the additive model (OR: 1.06, 95 % CI: 0.96-1.26; p = 0.49, the recessive genetic model (OR: 1.05, 95 % CI: 0.65-1.70; p = 0.85 or the dominant genetic model (OR: 1.07, 95 % CI: 0.87-1.32; p = 0.53. Similarly, no significant relationship was observed in the stratified analysis by ethnicity, study design and Hardy-Weinberg equilibrium (all p > 0.05. In the non-smokers, however, hOGG1 326Cys allele significantly increased the risk for bladder cancer and the ORs in the additive model, homozygote contrast and recessive genetic model were 1.59 (p = 0.02, 2.53(p = 0.003 and 2.41(p = 0.0005, respectively. Nevertheless, in the smoker subgroup, similar findings could not be found in all genetic models (all p > 0.05. Conclusions The association between the hOGG1 326Cys allele and bladder cancer was significant in non-smoker population, while was non-detectable in

  13. Estimation of risk of developing bladder cancer among workers exposed to coal tar pitch volatiles in the primary aluminum industry.

    Science.gov (United States)

    Tremblay, C; Armstrong, B; Thériault, G; Brodeur, J

    1995-03-01

    To confirm the relationship between exposure to coal tar pitch volatiles and bladder cancer among primary aluminum production workers, we carried out a case-control study among blue-collar workers who had worked more than 1 year between 1950-1979 in a major plant using mostly the Soderberg process in the Province of Québec. Cases of bladder cancer (ICD code 188) diagnosed between 1970-1979 (n = 69) were mostly included in a previously reported study. To these were added cases diagnosed between 1980-1988 (n = 69). Each case was matched to three controls on date of birth, date of hiring, and length of service at the company. Smoking habits were assessed from the medical records at the company. Benzene-soluble matter (BSM) and benzo(a)pyrene (BaP) were used as indicators of environmental exposure to coal tar pitch volatiles in the workplace. The estimated risk for current smokers was 2.63 (95% C.I. 1.29-5.37). Estimates of risk by occupational exposure were adjusted for smoking. Men who had worked in the Soderberg potrooms were at higher risk of developing the disease, the risk increasing with the time spent in these departments. Similarly, a strong association between risk and cumulative exposure to BSM or to BaP was observed. The risks associated with cumulative exposure to BSM (mg/m3-years) and to BaP (microgram/m3-years) were described with mathematical models. Using a linear model (1 + bx) and lagging 10 years before the diagnosis, BaP cumulative exposure was a better indicator of risk than BSM cumulative exposure. The risk for each year of exposure to BaP at a concentration of 1 microgram/m3 increased by 1.7% (0.8%-3.2%). Using the same model for BSM, a worker exposed to the current threshold limit value of 0.2 mg/m3 for 40 years will sustain a risk of 2.22 (1.56-3.48). Comparison of risks according to different periods of diagnosis (1970-1979 vs. 1980-1988) did not reveal any significant temporal changes on risk estimates.

  14. Future directions in bladder cancer immunotherapy: towards adaptive immunity.

    Science.gov (United States)

    Smith, Sean G; Zaharoff, David A

    2016-01-01

    The clinical management of bladder cancer has not changed significantly in several decades. In particular, intravesical bacillus Calmette-Guérin (BCG) immunotherapy has been a mainstay for high-risk nonmuscle invasive bladder cancer since the late 1970s/early 1980s. This is despite the fact that bladder cancer has the highest recurrence rates of any cancer and BCG immunotherapy has not been shown to induce a tumor-specific immune response. We and others have hypothesized that immunotherapies capable of inducing tumor-specific adaptive immunity are needed to impact bladder cancer morbidity and mortality. This article summarizes the preclinical and clinical development of bladder cancer immunotherapies with an emphasis on the last 5 years. Expected progress in the near future is also discussed.

  15. Refinement of the prediction of N-acetyltransferase 2 (NAT2) phenotypes with respect to enzyme activity and urinary bladder cancer risk.

    Science.gov (United States)

    Selinski, Silvia; Blaszkewicz, Meinolf; Ickstadt, Katja; Hengstler, Jan G; Golka, Klaus

    2013-12-01

    Polymorphisms of N-acetyltransferase 2 (NAT2) are well known to modify urinary bladder cancer risk as well as efficacy and toxicity of pharmaceuticals via reduction in the enzyme's acetylation capacity. Nevertheless, the discussion about optimal NAT2 phenotype prediction, particularly differentiation between different degrees of slow acetylation, is still controversial. Therefore, we investigated the impact of single nucleotide polymorphisms and their haplotypes on slow acetylation in vivo and on bladder cancer risk. For this purpose, we used a study cohort of 1,712 bladder cancer cases and 2,020 controls genotyped for NAT2 by RFLP-PCR and for the tagSNP rs1495741 by TaqMan(®) assay. A subgroup of 344 individuals was phenotyped by the caffeine test in vivo. We identified an 'ultra-slow' acetylator phenotype based on combined *6A/*6A, *6A/*7B and *7B/*7B genotypes containing the homozygous minor alleles of C282T (rs1041983, *6A, *7B) and G590A (rs1799930, *6A). 'Ultra-slow' acetylators have significantly about 32 and 46 % lower activities of caffeine metabolism compared with other slow acetylators and with the *5B/*5B genotypes, respectively (P < 0.01, both). The 'ultra-slow' genotype showed an association with bladder cancer risk in the univariate analysis (OR = 1.31, P = 0.012) and a trend adjusted for age, gender and smoking habits (OR = 1.22, P = 0.082). In contrast, slow acetylators in general were not associated with bladder cancer risk, neither in the univariate (OR = 1.02, P = 0.78) nor in the adjusted (OR = 0.98, P = 0.77) analysis. In conclusion, this study suggests that NAT2 phenotype prediction should be refined by consideration of an 'ultra-slow' acetylation genotype.

  16. Surveillance of bladder cancer

    NARCIS (Netherlands)

    M.M.N. van der Aa (Madelon)

    2009-01-01

    textabstractThe urinary bladder together with the pyelum, ureters and urethra form the urinary tract system (figure 1.1); the system that is responsible for the excretion and collection of urine. With approximately 357,000 new cases per year worldwide, tumours of the urinary tract system contribute

  17. Adaptive radiotherapy for bladder cancer using deformable image registration of empty and full bladder

    DEFF Research Database (Denmark)

    Juneja, Prabhjot; Caine, H.; Hunt, P.;

    2015-01-01

    A common objective of various adaptive radiotherapy (ART) strategies for bladder cancer is to reduce irradiation of normal tissue, thereby reduce the risk of radiation induced toxicity, and maintain or improve the target coverage. Bladder radiotherapy, typically involves generous margins (up to 20...... that incorporates the extreme deformations of the bladder, and is applicable from the first day of treatment. Deformation vector fields (DVFs), measured from the deformable image registration between empty and full bladder CTs, were scaled and constrained to construct the a-PTVs. For each patient, four a-PTVs were...

  18. Evaluation of a Bladder Cancer Cluster in a Population of Criminal Investigators with the Bureau of Alcohol, Tobacco, Firearms and Explosives—Part 2: The Association of Cancer Risk and Fire Scene Investigation

    Directory of Open Access Journals (Sweden)

    Susan R. Davis

    2013-01-01

    Full Text Available This study evaluated the association of bladder cancer risk and fire scene investigation within a cohort of white male criminal investigators with the United States Bureau of Alcohol, Tobacco, Firearms and Explosives that was found to be at increased risk for bladder cancer. Medical surveillance data were used in a nested case-control study to determine odds ratios (ORs estimating the relative risk of the cancer associated with post-fire investigation. The study comprised seven bladder cancer cases and 1525 controls. Six of the cases reported holding assignments associated with post-fire investigation. The OR for bladder cancer was 19.01 (95% confidence interval = 1.94–186.39 for those holding any one or more of these assignments for one to four years versus zero years and 12.56 (1.14–138.58 for those holding any one or more of these assignments for five or more years versus zero years. The risk for bladder cancer is significantly elevated for those holding post-fire investigation assignments compared to those not holding these assignments.

  19. Evaluation of a bladder cancer cluster in a population of criminal investigators with the Bureau of Alcohol, Tobacco, Firearms and Explosives--part 2: the association of cancer risk and fire scene investigation.

    Science.gov (United States)

    Davis, Susan R; Tao, Xuguang; Bernacki, Edward J; Alfriend, Amy S; Delowery, Mark E

    2013-01-01

    This study evaluated the association of bladder cancer risk and fire scene investigation within a cohort of white male criminal investigators with the United States Bureau of Alcohol, Tobacco, Firearms and Explosives that was found to be at increased risk for bladder cancer. Medical surveillance data were used in a nested case-control study to determine odds ratios (ORs) estimating the relative risk of the cancer associated with post-fire investigation. The study comprised seven bladder cancer cases and 1525 controls. Six of the cases reported holding assignments associated with post-fire investigation. The OR for bladder cancer was 19.01 (95% confidence interval = 1.94-186.39) for those holding any one or more of these assignments for one to four years versus zero years and 12.56 (1.14-138.58) for those holding any one or more of these assignments for five or more years versus zero years. The risk for bladder cancer is significantly elevated for those holding post-fire investigation assignments compared to those not holding these assignments.

  20. Metabolic phenotype of bladder cancer.

    Science.gov (United States)

    Massari, Francesco; Ciccarese, Chiara; Santoni, Matteo; Iacovelli, Roberto; Mazzucchelli, Roberta; Piva, Francesco; Scarpelli, Marina; Berardi, Rossana; Tortora, Giampaolo; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo

    2016-04-01

    Metabolism of bladder cancer represents a key issue for cancer research. Several metabolic altered pathways are involved in bladder tumorigenesis, representing therefore interesting targets for therapy. Tumor cells, including urothelial cancer cells, rely on a peculiar shift to aerobic glycolysis-dependent metabolism (the Warburg-effect) as the main energy source to sustain their uncontrolled growth and proliferation. Therefore, the high glycolytic flux depends on the overexpression of glycolysis-related genes (SRC-3, glucose transporter type 1 [GLUT1], GLUT3, lactic dehydrogenase A [LDHA], LDHB, hexokinase 1 [HK1], HK2, pyruvate kinase type M [PKM], and hypoxia-inducible factor 1-alpha [HIF-1α]), resulting in an overproduction of pyruvate, alanine and lactate. Concurrently, bladder cancer metabolism displays an increased expression of genes favoring the pentose phosphate pathway (glucose-6-phosphate dehydrogenase [G6PD]) and the fatty-acid synthesis (fatty acid synthase [FASN]), along with a decrease of AMP-activated protein kinase (AMPK) and Krebs cycle activities. Moreover, the PTEN/PI3K/AKT/mTOR pathway, hyper-activated in bladder cancer, acts as central regulator of aerobic glycolysis, hence contributing to cancer metabolic switch and tumor cell proliferation. Besides glycolysis, glycogen metabolism pathway plays a robust role in bladder cancer development. In particular, the overexpression of GLUT-1, the loss of the tumor suppressor glycogen debranching enzyme amylo-α-1,6-glucosidase, 4-α-glucanotransferase (AGL), and the increased activity of the tumor promoter enzyme glycogen phosphorylase impair glycogen metabolism. An increase in glucose uptake, decrease in normal cellular glycogen storage, and overproduction of lactate are consequences of decreased oxidative phosphorylation and inability to reuse glucose into the pentose phosphate and de novo fatty acid synthesis pathways. Moreover, AGL loss determines augmented levels of the serine-to-glycine enzyme

  1. The Danish Bladder Cancer Database

    DEFF Research Database (Denmark)

    Hansen, Erik; Larsson, Heidi Jeanet; Nørgaard, Mette

    2016-01-01

    -year mortality following curative-intended radiation therapy was 32% (95% CI: 24-39) and 1-year cancer-specific mortality was 23% (95% CI: 16-31) in 2013. CONCLUSION: This preliminary DaBlaCa-data report showed that the treatment of MIBC in Denmark overall meet high international academic standards. The database......AIM OF DATABASE: The aim of the Danish Bladder Cancer Database (DaBlaCa-data) is to monitor the treatment of all patients diagnosed with invasive bladder cancer (BC) in Denmark. STUDY POPULATION: All patients diagnosed with BC in Denmark from 2012 onward were included in the study. Results...... presented in this paper are predominantly from the 2013 population. MAIN VARIABLES: In 2013, 970 patients were diagnosed with BC in Denmark and were included in a preliminary report from the database. A total of 458 (47%) patients were diagnosed with non-muscle-invasive BC (non-MIBC) and 512 (53%) were...

  2. Hypertension, diuretics and antihypertensives in relation to bladder cancer

    Science.gov (United States)

    Jiang, Xuejuan; Castelao, J.Esteban; Yuan, Jian-Min; Groshen, Susan; Stern, Mariana C.; Conti, David V.; Cortessis, Victoria K.; Coetzee, Gerhard A.; Pike, Malcolm C.; Gago-Dominguez, Manuela

    2010-01-01

    The aim of this study is to investigate the relationships between hypertension, hypertension medication and bladder cancer risk in a population-based case–control study conducted in Los Angeles. Non-Asians between the ages of 25 and 64 years with histologically confirmed bladder cancers diagnosed between 1987 and 1996 were identified through the Los Angeles County Cancer Surveillance Program. A total of 1585 cases and their age-, gender- and race-matched neighborhood controls were included in the analyses. Conditional logistic regression models were used to examine the relationship between history of hypertension, medication use and bladder cancer risk. A history of hypertension was not related to bladder cancer; however, among hypertensive individuals, there was a significant difference in bladder cancer risk related to the use of diuretics or antihypertensive drugs (P for heterogeneity = 0.004). Compared with individuals without hypertension, hypertensive individuals who regularly used diuretics/antihypertensives had a similar risk [odds ratio (OR) 1.06; 95% confidence interval (CI) 0.86–1.30], whereas untreated hypertensive subjects had a 35% reduction in risk (OR: 0.65; 95% CI: 0.48–0.88). A greater reduction in bladder cancer risk was observed among current-smokers (OR: 0.43; 95% CI: 0.27–0.71) and carriers of GSTM1-null (homozygous absence) genotypes (OR: 0.43; 95% CI: 0.22–0.85). Similarly, among smokers with GSTM1-null genotype, levels of 4-aminobiphenyl-hemoglobin adducts were significantly lower among untreated hypertensive individuals (45.7 pg/g Hb) compared with individuals without hypertension (79.8 pg/g Hb) (P = 0.009). In conclusion, untreated hypertension was associated with a reduced risk of bladder cancer. PMID:20732908

  3. Management of the urethra in urothelial bladder cancer

    OpenAIRE

    Kanaroglou, Androniki; Shayegan, Bobby

    2009-01-01

    The standard of care in the management of invasive urothelial cancer of the bladder is radical cystectomy and pelvic lymphadenectomy. Although uncommon, recurrence of disease in the retained urethra following cystectomy carries a poor prognosis. The need for assessment of risk of recurrence is greater now than ever with wider adoption of orthotopic bladder substitution. This review will address the contemporary management of the urethra following cystectomy for urothelial cancer.

  4. Spectroscopic Imaging of Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Demos, S G; Gandour-Edwards, R; Ramsamooj, R; deVere White, R

    2003-01-01

    The feasibility of developing bladder cancer detection methods using intrinsic tissue optical properties is the focus of this investigation. In vitro experiments have been performed using polarized elastic light scattering in combination with tissue autofluorescence in the NIR spectral region under laser excitation in the green and red spectral regions. The experimental results obtained from a set of tissue specimens from 25 patients reveal the presence of optical fingerprint characteristics suitable for cancer detection with high contrast and accuracy. These photonic methods are compatible with existing endoscopic imaging modalities which make them suitable for in-vivo application.

  5. Stages of Bladder Cancer

    Science.gov (United States)

    ... from a well that has high levels of arsenic . Drinking water that has been treated with chlorine . ... of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative ...

  6. Occupational exposure to solvents and bladder cancer

    DEFF Research Database (Denmark)

    Hadkhale, Kishor; Martinsen, Jan Ivar; Weiderpass, Elisabete;

    2017-01-01

    logistic regression model was used to estimate hazard ratios (HR) and their 95% confidence intervals (95% CI). Increased risks were observed for trichloroethylene (HR 1.23, 95% 95% CI 1.12-1.40), toluene (HR 1.20, 95% CI 1.00-1.38), benzene (HR 1.16, 95% CI 1.04-1.31), aromatic hydrocarbon solvents (HR 1...... of occupational exposure to trichloroethylene, perchloroethylene, aromatic hydrocarbon solvents, benzene and toluene and the risk of bladder cancer. This article is protected by copyright. All rights reserved....

  7. CYP1A1 (Ile462Val), CYP1B1 (Ala119Ser and Val432Leu), GSTM1 (null), and GSTT1 (null) polymorphisms and bladder cancer risk in a Turkish population.

    Science.gov (United States)

    Berber, Ufuk; Yilmaz, Ismail; Yilmaz, Omer; Haholu, Aptullah; Kucukodaci, Zafer; Ates, Ferhat; Demirel, Dilaver

    2013-01-01

    We aimed to investigate bladder cancer risk with reference to polymorphic variants of cytochrome p450 (CYP) 1A1, CYP1B1, glutathione S-transferase (GST) M1, and GSTT1 genes in a case control study. Polymorphisms were examined in 114 bladder cancer patients and 114 age and sex-matched cancer-free subjects. Genotypes were determined using allele specific PCR for CYP1A1 and CYP1B1 genes, and by multiplex PCR and melting curve analysis for GSTM1 and GSTT1 genes. Our results revealed a statistically significant increased bladder cancer risk for GSTT1 null genotype carriers with an odds ratio of 3.06 (95% confidence interval=1.39-6.74, p=0.006). Differences of CYP1A1, CYP1B1 and GSTM1 genotype frequencies were not statistically significant between patients and controls. However, the specific combination of GSTM1 null, GSTT1 null, and CYP1B1 codon 119 risk allele carriers and specific combination of GSTM1 present, GSTT1 null, and CYP1B1 432 risk allele carriers exhibited increased cancer risk in the combined analysis. We did not observe any association between different genotype groups and prognostic tumor characteristics of bladder cancer. Our results indicate that inherited absence of GSTT1 gene may be associated with bladder cancer susceptibility, and specific combinations of GSTM1, GSTT1 and CYP1B1 gene polymorphisms may modify bladder cancer risk in the Turkish population, without any association being observed for CYP1A1 gene polymorphism and bladder cancer risk.

  8. Dietary intake of vegetables and fruits and the modification effects of GSTM1 and NAT2 genotypes on bladder cancer risk.

    Science.gov (United States)

    Lin, Jie; Kamat, Ashish; Gu, Jian; Chen, Meng; Dinney, Colin P; Forman, Michele R; Wu, Xifeng

    2009-07-01

    We analyzed the association between intakes of vegetables and fruits as defined by the U.S. Department of Agriculture pyramid food groups and bladder cancer risk using data collected in a large case-control study. The study included 884 histologically confirmed bladder cancer cases and 878 healthy controls matched to cases by age (+/-5 years), gender, and ethnicity. Significant inverse associations were observed for intakes of total vegetables, cruciferous vegetables, orange vegetables, dark green vegetables, and bladder cancer risk. Compared with those in the lowest quartile of total vegetable intake, the odds ratios for the 2nd, 3rd, and 4th quartiles of total vegetable intake were 0.84 [95% confidence interval (95% CI), 0.64-1.10], 0.71 (95% CI, 0.54-0.95), and 0.67 (95% CI, 0.50-0.90), respectively (P for trend = 0.004). Compared with those in the lowest quartile, those in the highest quartile of cruciferous vegetable intake had an odds ratio of 0.69 (95% CI, 0.52-0.92; P for trend = 0.001) and those in the highest quartile of orange vegetable intake had an odds ratio of 0.68 (95% CI, 0.52-0.91; P for trend = 0.006). Furthermore, the protective effect of cruciferous vegetables was more evident in subjects carrying GSTM1-null (odds ratio, 0.43; 95% CI, 0.25-0.73 for the 4th quartile of intake) and NAT2-slow genotypes (odds ratio, 0.56; 95% CI, 0.33-0.97 for the 4th quartile of intake). No association was observed for intakes of total fruits or citrus fruits. Our data strongly support that high vegetable consumption, especially cruciferous vegetable intake, may protect against bladder cancer and that genetic variants of GSTM1 and NAT2 may modify the association.

  9. Parity, Age at First Birth, and Risk of Death from Bladder Cancer: A Population-Based Cohort Study in Taiwan

    Science.gov (United States)

    Chiu, Hui-Fen; Chen, Brian K.; Yang, Chun-Yuh

    2016-01-01

    The evidence is limited on the relationship between reproductive factors and bladder cancer (BC). We studied 1,292,462 women who had a first and singleton delivery between 1 January 1978 and 31 December 1987. Each woman in the study cohort was tracked from their first childbirth to 31 December 2009. Vital status of the women was determined by crosswalking records with a computerized mortality database. We used Cox proportional hazard regression models to estimate the hazard ratios (HRs) of death from BC associated with maternal age at first birth and parity. The data showed 63 BC deaths during 34,980,246 person-years of follow-up. BC mortality rate was 0.90 cases for every 100,000 person-years. Compared with women who gave birth under the age of 23, the adjusted HR was 1.24 (95% confidence interval (CI) = 0.66–2.35) for women who gave birth between age 23 and 26 and 2.30 (95% CI = 1.21–4.39) for women who gave birth over the age of 26. Increasing age at first birth (p for trend = 0.01) is associated with a trend in increasing risk of BC mortality. Relative to women who had a single childbirth, the adjusted HRs were 1.17 (95% CI = 0.51–2.69) for women who gave birth to two children, and 1.31 (95% CI = 0.56–3.10) for women with three or more childbirths, respectively. These results were not statistically significant. Study results suggests that giving birth at an early age may confer a protective effect on the risk of death from BC. PMID:27918463

  10. Urinary Bladder Cancer in Yemen

    Science.gov (United States)

    Al-Samawi, Abdullah Saleh; Aulaqi, Saleh Mansoor

    2013-01-01

    Objectives The aims of this study are to highlight the clinicopathological features of urinary bladder cancer in Yemen, and to describe the histological grading of urothelial neoplasms according to the World Health Organization and International Society of Urologic pathology (WHO/ISUP 1998) classification. Methods This is a descriptive record-based study of 316 cases of bladder cancer diagnosed by two pathologists at the Department of pathology, Sana'a University from 1st January 2005 to 30th April 2009. The diagnoses were made on hematoxylin and eosin stained sections and categorized according to WHO/ISUP 1998 classification. Results Out of 316 urinary bladder cancers, 248 (78%) were urothelial neoplasms, 53 (17%) were squamous cell carcinoma, 7 (2%) were adenocarcinoma, and 3 (1%) were rhabdomyosarcoma. The remaining cases were metastatic carcinomas (n=3), small cell carcinoma (n=1), and non-Hodgkin's lymphoma (n=1). The urothelial neoplasms observed were carcinoma in situ 4 (2%), papilloma 7 (3%), papillary urothelial neoplasm of low malignant potential 26 (11%), papillary urothelial carcinoma of low grade 107 (43%), papillary urothelial carcinoma of high grade 18 (7%), and non-papillary urothelial carcinoma of high grade 85 (34%), with 60 years mean age for males and 58 years for females; along with a male to female ratio of 4:1. The peak incidence was observed in the 61-70 years age group. Conclusion This study documents a high frequency of urothelial neoplasms, mostly papillary urothelial carcinoma of low grade and non-papillary urothelial carcinoma of high grade with male preponderance and peak incidence in 6th decade of age. PMID:24044060

  11. Urinary Bladder Cancer in Yemen

    Directory of Open Access Journals (Sweden)

    Abdullah Saleh Al-Samawi

    2013-09-01

    Full Text Available Objectives: The aims of this study are to highlight the clinicopathological features of urinary bladder cancer in Yemen, and to describe the histological grading of urothelial neoplasms according to the World Health Organization and International Society of Urologic pathology (WHO/ISUP 1998 classification.Methods: This is a descriptive record-based study of 316 cases of bladder cancer diagnosed by two pathologists at the Department of pathology, Sana'a University from 1st January 2005 to 30th April 2009. The diagnoses were made on hematoxylin and eosin stained sections and categorized according to WHO/ISUP 1998 classification.Results: Out of 316 urinary bladder cancers, 248 (78% were urothelial neoplasms, 53 (17% were squamous cell carcinoma, 7 (2% were adenocarcinoma, and 3 (1% were rhabdomyosarcoma. The remaining cases were metastatic carcinomas (n=3, small cell carcinoma (n=1, and non-Hodgkin's lymphoma (n=1. The urothelial neoplasms observed were carcinoma in situ 4 (2%, papilloma 7 (3%, papillary urothelial neoplasm of low malignant potential 26 (11%, papillary urothelial carcinoma of low grade 107 (43%, papillary urothelial carcinoma of high grade 18 (7%, and non-papillary urothelial carcinoma of high grade 85 (34%, with 60 years mean age for males and 58 years for females; along with a male to female ratio of 4:1. The peak incidence was observed in the 61-70 years age group.Conclusion: This study documents a high frequency of urothelial neoplasms, mostly papillary urothelial carcinoma of low grade and non-papillary urothelial carcinoma of high grade with male preponderance and peak incidence in 6th decade of age.

  12. Novel non invasive diagnostic strategies in bladder cancer.

    Science.gov (United States)

    Truta, Anamaria; Popon, Tudor Adrian Hodor; Saraci, George; Ghervan, Liviu; Pop, Ioan Victor

    2016-01-01

    Bladder cancer is one of the most commonly diagnosed malignancies worldwide, derived from the urothelium of the urinary bladder and defined by long asymptomatic and atypical clinical picture. Its complex etiopathogenesis is dependent on numerous risk factors that can be divided into three distinct categories: genetic and molecular abnormalities, chemical or environmental exposure and previous genitourinary disorders and family history of different malignancies. Various genetic polymorphisms and microRNA might represent useful diagnostic or prognostic biomarkers. Genetic and molecular abnormalities - risk factors are represented by miRNA or genetic polymorphisms proved to be part of bladder carcinogenesis such as: genetic mutations of oncogenes TP53, Ras, Rb1 or p21 oncoproteins, cyclin D or genetic polymorhisms of XPD,ERCC1, CYP1B1, NQO1C609T, MDM2SNP309, CHEK2, ERCC6, NRF2, NQO1Pro187Ser polymorphism and microRNA (miR-143, -145, -222, -210, -10b, 576-3p). The aim of our article is to highlight the most recent acquisitions via molecular biomarkers (miRNAs and genetic polymorphisms) involved in bladder cancer in order to provide early diagnosis, precise therapy according to the molecular profile of bladder tumors, as well as to improve clinical outcome, survival rates and life quality of oncological patients. These molecular biomarkers play a key role in bladder carcinogenesis, clinical evolution, prognosis and therapeutic response and explain the molecular mechanisms involved in bladder carcinogenesis; they can also be selected as therapeutic targets in developing novel therapeutic strategies in bladder malignancies. Moreover, the purpose in defining these molecular non invasive biomarkers is also to develop non invasive screening programs in bladder malignancies with the result of decreasing bladder cancer incidence in risk population.

  13. Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

    NARCIS (Netherlands)

    Zamora-Ros, R.; Sacerdote, C.; Ricceri, F.; Weiderpass, E.; Roswall, N.; Buckland, G.; St-Jules, D.E.; Overvad, K.; Kyro, C.; Fagherazzi, G.; Kvaskoff, M.; Severi, G.; Chang-Claude, J.; Kaaks, R.; Nothlings, U.; Trichopoulou, A.; Naska, A.; Trichopoulos, D.; Palli, D.; Grioni, S.; Mattiello, A.; Tumino, R.; Gram, I.T.; Engeset, D.; Huerta, J.M.; Molina-Montes, E.; Arguelles, M.; Amiano, P.; Ardanaz, E.; Ericson, U.; Lindkvist, B.; Nilsson, L.M.; Kiemeney, L.A.L.M.; Ros, M.; Bueno-De-Mesquita, H.B.; Peeters, P.H.M.; Khaw, K.T.; Wareham, N.J.; Knaze, V.; Romieu, I.; Scalbert, A.; Brennan, P.; Wark, P.; Vineis, P.; Riboli, E.; Gonzalez, C.A.

    2014-01-01

    BACKGROUND: There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of

  14. Rs11892031[A] on chromosome 2q37 in an intronic region of the UGT1A locus is associated with urinary bladder cancer risk.

    Science.gov (United States)

    Selinski, Silvia; Lehmann, Marie-Louise; Blaszkewicz, Meinolf; Ovsiannikov, Daniel; Moormann, Oliver; Guballa, Christoph; Kress, Alexander; Truss, Michael C; Gerullis, Holger; Otto, Thomas; Barski, Dimitri; Niegisch, Günter; Albers, Peter; Frees, Sebastian; Brenner, Walburgis; Thüroff, Joachim W; Angeli-Greaves, Miriam; Seidel, Thilo; Roth, Gerhard; Volkert, Frank; Ebbinghaus, Rainer; Prager, Hans M; Bolt, Hermann M; Falkenstein, Michael; Zimmermann, Anna; Klein, Torsten; Reckwitz, Thomas; Roemer, Hermann C; Hartel, Mark; Weistenhöfer, Wobbeke; Schöps, Wolfgang; Rizvi, S Adibul Hassan; Aslam, Muhammad; Bánfi, Gergely; Romics, Imre; Ickstadt, Katja; Hengstler, Jan G; Golka, Klaus

    2012-09-01

    Recently, rs11892031[A] has been identified in a genome-wide association study (GWAS) to confer increased risk of urinary bladder cancer (UBC). To confirm this association and additionally study a possible relevance of exposure to urinary bladder carcinogens, we investigated the IfADo UBC study group, consisting of eight case-control series from different regions including 1,805 cases and 2,141 controls. This analysis was supplemented by a meta-analysis of all published data, including 13,395 cases and 54,876 controls. Rs11892031 A/A was significantly associated with UBC risk in the IfADo case-control series adjusted to cigarette smoking, gender, age and ethnicity (OR = 1.18; 95% CI = 1.02-1.37; P = 0.026). In the meta-analysis, a convincing association with UBC risk was obtained (OR = 1.19; 95% Cl = 1.12-1.26; P < 0.0001). Interestingly, the highest odds ratios were obtained for individual case-control series with a high degree of occupational exposure to polycyclic aromatic hydrocarbons and aromatic amines: cases with suspected occupational UBC (OR = 1.41) and cases from the highly industrialized Ruhr area (OR = 1.98) compared with Ruhr area controls (all combined OR = 1.46). Odds ratios were lower for study groups with no or a lower degree of occupational exposure to bladder carcinogens, such as the Hungary (OR = 1.02) or the ongoing West German case-control series (OR = 1.06). However, the possible association of rs11892031[A] with exposure to bladder carcinogens still should be interpreted with caution, because in contrast to the differences between the individual study groups, interview-based data on occupational exposure were not significantly associated with rs11892031. In conclusion, the association of rs11892031[A] with UBC risk could be confirmed in independent study groups.

  15. Photodynamic management of bladder cancer

    Science.gov (United States)

    Johansson, A.; Stepp, H.; Beyer, W.; Pongratz, T.; Sroka, R.; Bader, M.; Kriegmair, M.; Zaak, D.; Waidelich, R.; Karl, A.; Hofstetter, A.; Stief, C.; Baumgartner, R.

    2009-06-01

    Bladder cancer (BC) is among the most expensive oncological diseases. Any improvement in diagnosis or therapy carries a high potential for reducing costs. Fluorescence cystoscopy relies on a selective formation of Protoporphyrin IX (PpIX) or more general photoactive porphyrins (PAP) in malignant urothelium upon instillation of 5-aminolevulinic acid (5-ALA) or its hexyl-derivative h-ALA. Fluorescence cystoscopy equipment has been developed with the aim to compensate for the undesired distortion caused by the tissue optical properties by displaying the red fluorescence simultaneously with the backscattered blue light. Many clinical studies proved a high sensitivity in detecting flat carcinoma in situ and small papillary malignant tumours. As a result, recurrence rates were significantly decreased in most studies. The limitation lies in a low specificity, caused by false positive findings at inflamed bladder wall. Optical coherence tomography (OCT) is currently being investigated as a promising tool to overcome this limitation. H-ALA-PDT (8 or 16 mM h-ALA in 50 ml instillation for 1-2 h, white light source, catheter applicator) has recently been investigated in a phase I study. 17 patients were applied 100 J/cm2 (3 patients received incrementing doses of 25 - 50 - 100 J/cm2) during approx. 1 hour irradiation time in 3 sessions, 6 weeks apart. PDT was performed without any technical complications. Complete photobleaching of the PpIX-fluorescence, as intended, could be achieved in 43 of 45 PDT-sessions receiving 100 J/cm2. The most prominent side effects were postoperative urgency and bladder pain, all symptoms being more severe after 16 mM h-ALA. Preliminary evaluation shows complete response assessed at 3 months after the third PDT-session (i.e. 6 months after first treatment) in 9 of 12 patients. 2 of these patients were free of recurrence until final follow-up at 84 weeks.

  16. Copy Number Analysis of 24 Oncogenes: MDM4 Identified as a Putative Marker for Low Recurrence Risk in Non Muscle Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Samanta Salvi

    2014-07-01

    Full Text Available Patients with non-muscle invasive bladder cancer (NMIBC generally have a high risk of relapsing locally after primary tumor resection. The search for new predictive markers of local recurrence thus represents an important goal for the management of this disease. We studied the copy number variations (CNVs of 24 oncogenes (MDM4, MYCN, ALK, PDGFRA, KIT, KDR, DHFR, EGFR, MET, SMO, FGFR1, MYC, ABL1, RET, CCND1, CCND2, CDK4, MDM2, AURKB, ERBB2, TOP2A, AURKA, AR and BRAF using multiplex ligation probe amplification technique to verify their role as predictive markers of recurrence. Formalin-fixed paraffin-embedded tissue samples from 43 patients who underwent transurethral resection of the bladder (TURB were used; 23 patients had relapsed and 20 were disease-free after 5 years. Amplification frequencies were analyzed for all genes and MDM4 was the only gene that showed significantly higher amplification in non recurrent patients than in recurrent ones (0.65 vs. 0.3; Fisher’s test p = 0.023. Recurrence-free survival analysis confirmed the predictive role of MDM4 (log-rank test p = 0.041. Our preliminary results indicate a putative role for the MDM4 gene in predicting local recurrence of bladder cancer. Confirmation of this hypothesis is needed in a larger cohort of NMIBC patients.

  17. NOTCH pathway inactivation promotes bladder cancer progression.

    Science.gov (United States)

    Maraver, Antonio; Fernandez-Marcos, Pablo J; Cash, Timothy P; Mendez-Pertuz, Marinela; Dueñas, Marta; Maietta, Paolo; Martinelli, Paola; Muñoz-Martin, Maribel; Martínez-Fernández, Mónica; Cañamero, Marta; Roncador, Giovanna; Martinez-Torrecuadrada, Jorge L; Grivas, Dimitrios; de la Pompa, Jose Luis; Valencia, Alfonso; Paramio, Jesús M; Real, Francisco X; Serrano, Manuel

    2015-02-01

    NOTCH signaling suppresses tumor growth and proliferation in several types of stratified epithelia. Here, we show that missense mutations in NOTCH1 and NOTCH2 found in human bladder cancers result in loss of function. In murine models, genetic ablation of the NOTCH pathway accelerated bladder tumorigenesis and promoted the formation of squamous cell carcinomas, with areas of mesenchymal features. Using bladder cancer cells, we determined that the NOTCH pathway stabilizes the epithelial phenotype through its effector HES1 and, consequently, loss of NOTCH activity favors the process of epithelial-mesenchymal transition. Evaluation of human bladder cancer samples revealed that tumors with low levels of HES1 present mesenchymal features and are more aggressive. Together, our results indicate that NOTCH serves as a tumor suppressor in the bladder and that loss of this pathway promotes mesenchymal and invasive features.

  18. Fruits and vegetables intake and risk of bladder cancer: a PRISMA-compliant systematic review and dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Xu, Chang; Zeng, Xian-Tao; Liu, Tong-Zu; Zhang, Chao; Yang, Zhong-Hua; Li, Sheng; Chen, Xiao-Yan

    2015-05-01

    Clinical practice recommends eating ≥2.5 cups of fruits and vegetables (FVs) each day for cancer prevention, in which the evidence from epidemiological studies for the association between FVs intake and bladder cancer (BC) prevention is inconsistent.We searched the PubMed, Embase, and Willy online Library for relevant studies published up to September 27, 2014. Prospective cohort studies investigated FVs intake, and the risk of BC with ≥3 categories of exposure was included. A dose-response meta-analysis was carried out to evaluate the association between FVs intake and risk of BC.Fourteen cohorts with 17 studies including 9447 cases were identified. No evidence of nonlinear association was examined between FVs intake and risk of BC. The summarized relevant risk (RR) of every 0.2 serving increment a day was 1.00 (95%CI: 0.99, 1.00; P = 0.17; I = 41.7%; n = 14) for total fruits; 0.99 (95%CI: 0.96, 1.01; P = 0.28; I = 37.0%; n = 13) for total vegetables; and 0.99 (95%CI: 0.97, 1.01; P = 0.24; I = 57.5%; n = 8) for both FVs. In further analysis, we observed inverse association between every 0.2 serving increment of green leafy vegetables intake a day and risk of BC (RR = 0.98, 95%CI: 0.96, 0.99; I = 0.0%; P cruciferous vegetables (RR = 0.97, 95%CI: 0.93, 1.01; P = 0.19; I = 55.8%; n = 8) nor for citrus (RR = 1.00, 95%CI: 1.00, 1.00; P = 0.83; I = 0.0%; n = 7). Subgroup analysis showed consistent results.Little evidence supports a beneficial effect for total fruits, vegetables, both FVs, and citrus intake against bladder cancer. Green leafy vegetables may help prevent bladder cancer.

  19. Urinary bladder cancer risk in relation to a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor-binding protein-3 (IGFBP3) gene.

    Science.gov (United States)

    Selinski, Silvia; Lehmann, Marie-Louise; Blaszkewicz, Meinolf; Ovsiannikov, Daniel; Moormann, Oliver; Guballa, Christoph; Kress, Alexander; Truss, Michael C; Gerullis, Holger; Otto, Thomas; Barski, Dimitri; Niegisch, Günter; Albers, Peter; Frees, Sebastian; Brenner, Walburgis; Thüroff, Joachim W; Angeli-Greaves, Miriam; Seidel, Thilo; Roth, Gerhard; Volkert, Frank; Ebbinghaus, Rainer; Prager, Hans-Martin; Lukas, Cordula; Bolt, Hermann M; Falkenstein, Michael; Zimmermann, Anna; Klein, Torsten; Reckwitz, Thomas; Roemer, Hermann C; Hartel, Mark; Weistenhöfer, Wobbeke; Schöps, Wolfgang; Rizvi, S Adibul Hassan; Aslam, Muhammad; Bánfi, Gergely; Romics, Imre; Ickstadt, Katja; Hengstler, Jan G; Golka, Klaus

    2012-02-01

    Currently, twelve validated genetic variants have been identified that are associated with urinary bladder cancer (UBC) risk. However, those validated variants explain only 5-10% of the overall inherited risk. In addition, there are more than 100 published polymorphisms still awaiting validation or disproval. A particularly promising of the latter unconfirmed polymorphisms is rs2854744 that recently has been published to be associated with UBC risk. The [A] allele of rs2854744 has been reported to be associated with a higher promoter activity of the insulin-like growth factor-binding protein-3 (IGFBP3) gene, which may lead to increased IGFBP-3 plasma levels and cancer risk. Therefore, we investigated the association of rs2854744 with UBC in the IfADo case-control series consisting of 1,450 cases and 1,725 controls from Germany, Hungary, Venezuela and Pakistan. No significant association of rs2854744 with UBC risk was obtained (all study groups combined: unadjusted P = 0.4446; adjusted for age, gender and smoking habits P = 0.6510), besides a small effect of the [A] allele in the Pakistani study group opposed to the original findings (unadjusted P = 0.0508, odds ratio (OR) = 1.43 for the multiplicative model) that diminished after adjustment for age, gender and smoking habits (P = 0.7871; OR = 0.93). Associations of rs2854744 with occupational exposure to urinary bladder carcinogens and smoking habits were also not present. A meta-analysis of all available case-control series including the original discovery study resulted in an OR of 1.00 (P = 0.9562). In conclusion, we could not confirm the recently published hypothesis that rs2854744 in the IGFBP3 gene is associated with UBC risk.

  20. Does occupational exposure to solvents and pesticides in association with glutathione S-transferase A1, M1, P1, and T1 polymorphisms increase the risk of bladder cancer? The Belgrade case-control study.

    Directory of Open Access Journals (Sweden)

    Marija G Matic

    Full Text Available OBJECTIVE: We investigated the role of the glutathione S-transferase A1, M1, P1 and T1 gene polymorphisms and potential effect modification by occupational exposure to different chemicals in Serbian bladder cancer male patients. PATIENTS AND METHODS: A hospital-based case-control study of bladder cancer in men comprised 143 histologically confirmed cases and 114 age-matched male controls. Deletion polymorphism of glutathione S-transferase M1 and T1 was identified by polymerase chain reaction method. Single nucleotide polymorphism of glutathione S-transferase A1 and P1 was identified by restriction fragment length polymorphism method. As a measure of effect size, odds ratio (OR with corresponding 95% confidence interval (95%CI was calculated. RESULTS: The glutathione S-transferase A1, T1 and P1 genotypes did not contribute independently toward the risk of bladder cancer, while the glutathione S-transferase M1-null genotype was overrepresented among cases (OR = 2.1, 95% CI = 1.1-4.2, p = 0.032. The most pronounced effect regarding occupational exposure to solvents and glutathione S-transferase genotype on bladder cancer risk was observed for the low activity glutathione S-transferase A1 genotype (OR = 9.2, 95% CI = 2.4-34.7, p = 0.001. The glutathione S-transferase M1-null genotype also enhanced the risk of bladder cancer among subjects exposed to solvents (OR = 6,5, 95% CI = 2.1-19.7, p = 0.001. The risk of bladder cancer development was 5.3-fold elevated among glutathione S-transferase T1-active patients exposed to solvents in comparison with glutathione S-transferase T1-active unexposed patients (95% CI = 1.9-15.1, p = 0.002. Moreover, men with glutathione S-transferase T1-active genotype exposed to pesticides exhibited 4.5 times higher risk in comparison with unexposed glutathione S-transferase T1-active subjects (95% CI = 0.9-22.5, p = 0.067. CONCLUSION: Null or low-activity genotypes of the

  1. Expression and Significance of Oct4 in Bladder Cancer

    Institute of Scientific and Technical Information of China (English)

    XU Kai; ZHU Zhaohui; ZENG Fuqing; DONG Jihua

    2007-01-01

    In order to detect the expression of Oct4 in bladder cancer tissue and cell line BIU-87, immunohistochemistry was used in 49 bladder cancer biopsy samples and immunofluorescence and reverse transcription-PCR were performed on bladder cancer cell line BIU-87. Forty of 49 bladdercancer samples showed the expression of Oct4 in about 0.6% cancer cells. The positive rate and den-sity of Oct4 expression had no obvious relationship with the grade, recurrence or metastasis of blad-der cancer (P0.05). A few Oct4 positive cells were found in bladder cancer cell line BlU-87, which was also confirmed by RT-PCR. This study indicated the existence of few Oct4 positive cells in bladder cancer, which may be the bladder cancer stem cells. This study may provide the foundation for isolation and identification of bladder cancer stem cells.

  2. [Influence of a priori parameters on bayesian relative risks estimations. Spatial distribution of bladder cancer in the urban area of Grenoble].

    Science.gov (United States)

    Colonna, M

    2006-12-01

    Bayesian estimates of disease relative risks is currently the gold standard in disease mapping when the disease is rare and/or when the geographical area is small. Its use has become quite easy with adhoc software. However, the implicit mechanisms of the choices made by the user must be clearly identified. We were interested here in the consequences of the choice of the hyper a priori parameters. We have compared results obtained using various hyper a priori parameters. The consequences of these choices are illustrated through the example of the incidence of bladder cancer among men in the urban area of Grenoble. We show that the risks can appear weak from a statistical point of view but important from an epidemiologic point of view in the presentation of the results.

  3. Pathway analysis of bladder cancer genome-wide association study identifies novel pathways involved in bladder cancer development

    Science.gov (United States)

    Chen, Meng; Rothman, Nathaniel; Ye, Yuanqing; Gu, Jian; Scheet, Paul A.; Huang, Maosheng; Chang, David W.; Dinney, Colin P.; Silverman, Debra T.; Figueroa, Jonine D.; Chanock, Stephen J.; Wu, Xifeng

    2016-01-01

    Genome-wide association studies (GWAS) are designed to identify individual regions associated with cancer risk, but only explain a small fraction of the inherited variability. Alternative approach analyzing genetic variants within biological pathways has been proposed to discover networks of susceptibility genes with additional effects. The gene set enrichment analysis (GSEA) may complement and expand traditional GWAS analysis to identify novel genes and pathways associated with bladder cancer risk. We selected three GSEA methods: Gen-Gen, Aligator, and the SNP Ratio Test to evaluate cellular signaling pathways involved in bladder cancer susceptibility in a Texas GWAS population. The candidate genetic polymorphisms from the significant pathway selected by GSEA were validated in an independent NCI GWAS. We identified 18 novel pathways (P < 0.05) significantly associated with bladder cancer risk. Five of the most promising pathways (P ≤ 0.001 in any of the three GSEA methods) among the 18 pathways included two cell cycle pathways and neural cell adhesion molecule (NCAM), platelet-derived growth factor (PDGF), and unfolded protein response pathways. We validated the candidate polymorphisms in the NCI GWAS and found variants of RAPGEF1, SKP1, HERPUD1, CACNB2, CACNA1C, CACNA1S, COL4A2, SRC, and CACNA1C were associated with bladder cancer risk. Two CCNE1 variants, rs8102137 and rs997669, from cell cycle pathways showed the strongest associations; the CCNE1 signal at 19q12 has already been reported in previous GWAS. These findings offer additional etiologic insights highlighting the specific genes and pathways associated with bladder cancer development. GSEA may be a complementary tool to GWAS to identify additional loci of cancer susceptibility.

  4. Progress in Personalizing Chemotherapy for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    James S. Chang

    2012-01-01

    Full Text Available Platinum-based chemotherapy is commonly used for the treatment of locally advanced and metastatic bladder cancer. However, there are currently no methods to predict chemotherapy response in this disease setting. A better understanding of the biology of bladder cancer has led to developments of molecular biomarkers that may help guide clinical decision making. These biomarkers, while promising, have not yet been validated in prospective trials and are not ready for clinical applications. As alkylating agents, platinum drugs kill cancer cells mainly through induction of DNA damage. A microdosing approach is currently being tested to determine if chemoresistance can be identified by measuring platinum-induced DNA damage using highly sensitive accelerator mass spectrometry technology. The hope is that these emerging strategies will help pave the road towards personalized therapy in advanced bladder cancer.

  5. Pathology of bilharzial bladder cancer.

    Science.gov (United States)

    Godwin, J T; Hanash, K

    1984-01-01

    Retrospective review of bladder carcinoma at this institution has revealed a high incidence of squamous cell carcinoma associated with bilharzia infection as has been found in other Mideast and African countries. Associated inflammatory and epithelial metaplastic changes were commonly noted and apparently represent early changes in the development of carcinoma, particularly in view of the progression from squamous metaplasia to in situ and infiltrating carcinoma observed in both bladder and ureter. The relationship between bilharzia infection and the development of bladder carcinoma has been postulated to be related to several factors; however, as yet the specific etiologic relationship and pathogenesis have not been defined.

  6. Current clinical practice gaps in the treatment of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) with emphasis on the use of bacillus Calmette-Guerin (BCG): results of an international individual patient data survey (IPDS)

    NARCIS (Netherlands)

    Witjes, J.A.; Palou, J.; Soloway, M.; Lamm, D.; Kamat, A.M.; Brausi, M.; Persad, R.; Buckley, R.; Colombel, M.; Bohle, A.

    2013-01-01

    OBJECTIVES: To examine the management of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), particularly with regard to the use of bacillus Calmette-Guerin (BCG) therapy, in North America and Europe. To compare NMIBC management practices to European Association of Urology (EAU)

  7. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim;

    2007-01-01

    the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed...... with the use of Medline; additional cited works not detected on the initial search regarding neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and chemotherapy for patients with metastatic urothelial cancer were reviewed. Evidence-based recommendations for diagnosis and management...... trials have yet compared survival with transurethral resection of bladder tumor alone versus cystectomy for the management of patients with muscle-invasive disease. Collaborative international adjuvant chemotherapy trials are needed to assist researchers in assessing the true value of adjuvant...

  8. Optimizing systemic therapy for bladder cancer.

    Science.gov (United States)

    Pal, Sumanta K; Milowsky, Matthew I; Plimack, Elizabeth R

    2013-07-01

    Over the past several decades, few new systemic agents have been incorporated into the treatment paradigm for bladder cancer. Platinum-based therapy remains the cornerstone of treatment in the perioperative and metastatic settings. Despite level one evidence, use of cisplatin-based therapy in the neoadjuvant setting has been dismal. Second-line therapy for metastatic disease has only modest activity with no survival benefit. However, the elucidation and investigation of novel molecular targets, new therapeutics, and associated biomarkers with strong biologic rationale are actively changing the landscape in bladder cancer. Although the field is moving rapidly, no new drug approvals are currently pending and a need remains to continue to educate the medical oncology and urology communities on the optimal use of currently available treatments. This article outlines the evidence, including that from prospective studies and meta-analyses, providing the basis for the current recommendations from NCCN, and details previous and ongoing studies of targeted therapy for bladder cancer.

  9. Paraneoplastic retinopathy associated with occult bladder cancer

    DEFF Research Database (Denmark)

    Nivean, M; Muttuvelu, Danson V; Afzelius, Pia Maria Tullia

    2016-01-01

    The aim was to report the first case of cancer-associated retinopathy (CAR) presenting before bladder cancer diagnosis. A 71-year-old woman with a history of bilateral vision loss underwent subsequent complete ophthalmic examination include a fluorescein angiography, full-field electroretinogram...... (ERG), serology including serum antibodies for CAR, and positron emission tomography-computed tomography (PET-CT) scan. The patient was diagnosed with bladder carcinoma revealed by PET-CT. Timely recognition of this entity may be crucial for an increased patient survival thus adult onset progressive...

  10. Deciphering the Roles of Thiazolidinediones and PPARγ in Bladder Cancer

    Science.gov (United States)

    Chiu, Melody; McBeth, Lucien; Sindhwani, Puneet

    2017-01-01

    The use of thiazolidinedione (TZD) therapy in type II diabetic patients has proven useful in the lowering of blood glucose levels. However, recent investigations have shown that there may be potential health concerns associated, including the risk of developing bladder cancer as well as complications in the cardiovasculature. TZDs are ligands for the nuclear receptor PPARγ, and activation causes lipid uptake and insulin sensitization, both of which are critical processes for diabetic patients whose bodies are unable to utilize insulin effectively. Several studies have shown that PPARγ/TZDs decrease IGF-1 levels and, thus, reduce cancer growth in carcinomas such as the pancreas, colon, liver, and prostate. However, other studies have shed light on the potential of the receptor as a biomarker for uroepithelial carcinomas, particularly due to its stimulatory effect on migration of bladder cancer cells. Furthermore, PPARγ may provide the tumor-promoting microenvironment by de novo synthesis of nutrients that are needed for bladder cancer development. In this review, we closely examine the TZD class of drugs and their effects on PPARγ in patient studies along with additional molecular factors that are positive modulators, such as protein phosphatase 5 (PP5), which may have considerable implications for bladder cancer therapy.

  11. Automatic staging of bladder cancer on CT urography

    Science.gov (United States)

    Garapati, Sankeerth S.; Hadjiiski, Lubomir M.; Cha, Kenny H.; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Weizer, Alon; Alva, Ajjai; Paramagul, Chintana; Wei, Jun; Zhou, Chuan

    2016-03-01

    Correct staging of bladder cancer is crucial for the decision of neoadjuvant chemotherapy treatment and minimizing the risk of under- or over-treatment. Subjectivity and variability of clinicians in utilizing available diagnostic information may lead to inaccuracy in staging bladder cancer. An objective decision support system that merges the information in a predictive model based on statistical outcomes of previous cases and machine learning may assist clinicians in making more accurate and consistent staging assessments. In this study, we developed a preliminary method to stage bladder cancer. With IRB approval, 42 bladder cancer cases with CTU scans were collected from patient files. The cases were classified into two classes based on pathological stage T2, which is the decision threshold for neoadjuvant chemotherapy treatment (i.e. for stage >=T2) clinically. There were 21 cancers below stage T2 and 21 cancers at stage T2 or above. All 42 lesions were automatically segmented using our auto-initialized cascaded level sets (AI-CALS) method. Morphological features were extracted, which were selected and merged by linear discriminant analysis (LDA) classifier. A leave-one-case-out resampling scheme was used to train and test the classifier using the 42 lesions. The classification accuracy was quantified using the area under the ROC curve (Az). The average training Az was 0.97 and the test Az was 0.85. The classifier consistently selected the lesion volume, a gray level feature and a contrast feature. This predictive model shows promise for assisting in assessing the bladder cancer stage.

  12. The Relationship between Food Intake and Bladder Cancer: A Case Control Study

    Directory of Open Access Journals (Sweden)

    2015-01-01

    Full Text Available Background & aim: Bladder cancer is the second most common cancer of the urinary tract worldwide and the third most common cancer among Iranian males. Despite the relative high incidence of bladder cancer in Iran, no study has examined the relationship between dietary factors and bladder cancer. The aim of the present study was to investigate this relationship. Methods: The present case-control study was carried out on fifty-five patients with bladder cancer and including 110 cancer-free patients as controls. Dietary intake was evaluated using a food frequency questionnaire. To investigate the relationship between food items and bladder cancer, the subjects were classified according to the tertile of food items. The odds ratio was calculated for each tertile and the first tertile was considered as the reference group. Results: Our findings revealed that among food groups, animal fat (OR=19.76, fat (OR=12.92, junk foods (OR=8.1, organ meat (OR=5.47, processed meat (OR=5.34 and sweets (OR=3.62 were involved in the development of bladder cancer. In bladder carcinogenesis, an inverse association was recorded between consumption of low fat dairy products (OR=0.31, yoghurt (OR =0.14, fish (OR = 0.13, specific fruits (OR=0.13 and the development of bladder cancer. Conclusion: Animal products and sources of saturated fat are associated with an increased in risk of bladder cancer. The protective effect of olive oil, specific fruits, vegetables, low-fat dairy fermented was observed to reduce the risk of bladder cancer.

  13. Natural biology and management of nonmuscle invasive bladder cancer

    DEFF Research Database (Denmark)

    Scarpato, Kristen R; Tyson, Mark D; Clark, Peter E

    2016-01-01

    PURPOSE OF REVIEW: This article reviews the natural biology of noninvasive bladder cancer and its management strategies while summarizing the most recent advances in the field. RECENT FINDINGS: Nonmuscle invasive bladder cancer (NMIBC) has a tendency to recur and progress. Risk stratification has...... treatment, especially in refractory high-risk cases, include the addition of intravesical hyperthermia, combination and sequential therapy with existing agents and the use of novel agents such as mycobacterial cell wall extract. New data are emerging regarding the potential role of active surveillance...... in low-risk patients. SUMMARY: NMIBC represents a variety of disease states and continues to pose management challenges. As our understanding of tumor biology improves and technology advances, achieving better outcomes through individualized care may be possible....

  14. Reducing aluminum: an occupation possibly associated with bladder cancer.

    Science.gov (United States)

    Thériault, G; De Guire, L; Cordier, S

    1981-02-15

    A case-control study, undertaken to identify reasons for the exceptionally high incidence of bladder cancer among men in the Chicoutimi census division of the province of Quebec, revealed an increased risk associated with employment in the electrolysis department of an aluminum reduction plant. The estimated relative risk was 2.83 (95% confidence interval; 1.06 to 7.54). An interaction was found between such employment and cigarette smoking, resulting in a combined relative risk of 5.70 (95% confidence interval: 2.00 to 12.30). These findings suggest that employment in an aluminum reduction plant accounts for part of the excess of bladder cancer in the region studied.

  15. Image-guided radiotherapy of bladder cancer: bladder volume variation and its relation to margins

    DEFF Research Database (Denmark)

    Muren, Ludvig; Redpath, Anthony Thomas; Lord, Hannah

    2007-01-01

    BACKGROUND AND PURPOSE: To control and account for bladder motion is a major challenge in radiotherapy (RT) of bladder cancer. This study investigates the relation between bladder volume variation and margins in conformal and image-guided RT (IGRT) for this disease. MATERIALS AND METHODS: The cor...

  16. Radical radiotherapy for urinary bladder cancer

    DEFF Research Database (Denmark)

    Fokdal, Lars; von der Maase, Hans; Høyer, Morten

    2006-01-01

    The exact value of radiotherapy in the treatment of muscle-invasive       bladder cancer is difficult to establish, as most studies exploring this       issue are retrospective with different procedures for selecting patients       for treatment, as well as varying treatment strategies. An estima...

  17. Impact of proteomics on bladder cancer research

    DEFF Research Database (Denmark)

    Celis, Julio E; Gromova, Irina; Moreira, José Manuel Alfonso

    2004-01-01

    Detecting bladder cancer at an early stage and predicting how a tumor will behave and act in response to therapy, as well as the identification of new targets for therapeutic intervention, are among the main areas of research that will benefit from the current explosion in the number of powerful ...

  18. Bladder cancer: molecular determinants of personalized therapy.

    Science.gov (United States)

    Lopez-Beltran, Antonio; Santoni, Matteo; Massari, Francesco; Ciccarese, Chiara; Tortora, Giampaolo; Cheng, Liang; Moch, Holger; Scarpelli, Marina; Reymundo, Carlos; Montironi, Rodolfo

    2015-01-01

    Several molecular and genetic studies have provided new perspectives on the histologic classification of bladder tumors. Recent developments in the field of molecular mutational pathway analyses based on next generation sequencing technology together with classic data derived from the description of mutations in the FGFR3 (fibroblast growth factor receptor 3) gene, mutations on TP53 gene, and cDNA technology profiling data gives support to a differentiated taxonomy of bladder cancer. All these changes are behind the use of non-traditional approach to therapy of bladder cancer patients and are ready to change our daily practice of uro-oncology. The observed correlation of some molecular alterations with tumor behavior and the identification of their targets at cellular level might support the use of molecular changes together with morphological data to develop new clinical and biological strategies to manage patients with urothelial cancer. The current review provides comprehensive data to support personalized therapy for bladder cancer based on an integrated approach including pathologic and clinical features and molecular biology.

  19. Utility of Clinical Risk Stratification in the Selection of Muscle-Invasive Bladder Cancer Patients for Neoadjuvant Chemotherapy: A Retrospective Cohort Study

    Science.gov (United States)

    von Rundstedt, Friedrich-Carl; Mata, Douglas A.; Kryvenko, Oleksandr N.; Shah, Anup A.; Jhun, Iny; Lerner, Seth P.

    2016-01-01

    Introduction: Level I evidence supports the use of cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer prior to radical cystectomy (RC). On average, 30–40% of patients achieve a complete pathologic response (i.e., stage pT0) after receiving NAC. Some centers risk-stratify patients, suggesting that there may be a higher-risk population that would derive the most benefit from NAC. Recently, a risk-stratification model developed at M.D. Anderson Cancer Center (MDACC) specified criteria for clinical staging and patient selection for NAC. We applied this model to our own RC patient cohort and evaluated our own experience with clinical risk stratification and the effect of NAC on post treatment risk categories. Methods: We retrospectively reviewed the charts of consecutive patients who underwent RC at two institutions between 2004 and 2014 and noted whether or not they received NAC. We determined the clinical stage by reviewing the exam under anesthesia, transurethral resection biopsy (TURBT) pathology, and preoperative imaging. Patients with cT2-T4a node-negative disease were included. Those with sarcomatoid features or adenocarcinoma were excluded. Patients were classified as high risk if they had tumor-associated hydronephrosis, clinical stage≥T3b-T4a disease, variant histology (i.e., micropapillary or small cell), or lymphovascular invasion (LVI), as specified by the MDACC model. Variables were examined for associations with cancer-specific survival (CSS), overall survival (OS), and risk-category reclassification. Results: We identified 166 patients with a median follow-up time of 22.2 months. In all, 117 patients (70.5%) did not receive NAC, 68 (58.1%) of whom we classified as high risk. Among patients not receiving NAC, CSS and OS were significantly decreased in high-risk patients (log-rank test p = 0.01 for both comparisons). The estimated age-adjusted hazard ratios of high-risk classification for cancer-specific and overall

  20. Chemoradiation May Help Some Patients with Bladder Cancer Avoid Radical Surgery

    Science.gov (United States)

    Researchers in the United Kingdom have found that adding chemotherapy to radiation therapy as a treatment for bladder cancer may reduce the risk of a recurrence more than radiation alone, without causing a substantial increase in side effects.

  1. Neoadjuvant Chemotherapy in Neuroendocrine Bladder Cancer: A Case Report

    OpenAIRE

    Prelaj, Arsela; Rebuzzi, Sara Elena; Magliocca, Fabio Massimo; Speranza, Iolanda; Corongiu, Emanuele; Borgoni, Giuseppe; Perugia, Giacomo; Liberti, Marcello; Bianco, Vincenzo

    2016-01-01

    Patient: Male, 71 Final Diagnosis: Neuroendocrine cancer bladder Symptoms: Dysuria • haematuria Medication: — Clinical Procedure: Transurethral resection of the bladder tumor Specialty: Oncology Objective: Rare disease Background: Small cell carcinoma of the urinary bladder is a rare and aggressive form of bladder cancer that mainly presents at an advanced stage. As a result of its rarity, it has been described in many case reports and reviews but few retrospective and prospective trials, sho...

  2. Are retinol, vitamin C, vitamin E, folate and carotenoids intake associated with bladder cancer risk? : results from the Netherlands cohort study

    NARCIS (Netherlands)

    Zeegers, M.P.A.; Goldbohm, R.A.; Brandt, P.A. van den

    2001-01-01

    In the Netherlands Cohort Study among 120 852 subjects aged 55-69 years at baseline (1986), the association between vitamins and carotenoids intake, vitamin supplement use, and bladder cancer incidence was examined. Exposure status was measured with a food-frequency questionnaire. After 6.3 years of

  3. Microsatellite instability in bladder cancer

    DEFF Research Database (Denmark)

    Gonzalez-Zulueta, M; Ruppert, J M; Tokino, K;

    1993-01-01

    Somatic instability at microsatellite repeats was detected in 6 of 200 transitional cell carcinomas of the bladder. Instabilities were apparent as changes in (GT)n repeat lengths on human chromosome 9 for four tumors and as alterations in a (CAG)n repeat in the androgen receptor gene on the X...... chromosome for three tumors. Single locus alterations were detected in three tumors, while three other tumors revealed changes in two or more loci. In one tumor we found microsatellite instability in all five loci analyzed on chromosome 9. The alterations detected were either minor 2-base pair changes...

  4. BK virus as a potential oncovirus for bladder cancer in a renal transplant patient.

    Science.gov (United States)

    Yin, Wen-Yao; Lee, Ming-Che; Lai, Ning-Sheng; Lu, Ming-Chi

    2015-04-01

    Renal transplant patients have high risk for bladder cancer. The reactivation of BK virus is common in renal transplant patients especially in the urinary tract. There was some evidence suggesting that the reactivation of BK virus (BKV) in renal transplant patients may associate with the development of bladder cancer. Here we demonstrated that a patient that had persistent elevated BKV viruria (urine BKV DNA concentration more than 10(11) copies/ml) after renal transplantation. Then, bladder cancer was found in 13 months after kidney transplantation. The urine BKV DNA concentration was detected by real-time PCR and the BKV DNA in the bladder tumor was detected by PCR. BKV DNA was found in the marginal and central part of the bladder tumor. After removal of the bladder cancer, the urine BKV viral load in this patients dropped dramatically to <10(2) copies/ml. However, the urine viral load had increased modestly to 10(6) copies/ml in 3 months after surgery. Since there is a close correlation between the urine BK viral load and the presence of bladder cancer, we suggested that there might be a causal relationship between the reactivation of BKV and the development of bladder cancer in renal transplant patient.

  5. Designing the selenium and bladder cancer trial (SELEBLAT, a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium

    Directory of Open Access Journals (Sweden)

    Goossens Maria E

    2012-03-01

    Full Text Available Abstract Background In Belgium, bladder cancer is the fifth most common cancer in males (5.2% and the sixth most frequent cause of death from cancer in males (3.8%. Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence. Method The SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at http://www.seleblat.org. Patients are randomly assigned to selenium yeast (200 μg/day supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study. Design The SELEnium and BLAdder cancer Trial (SELEBLAT is a phase III randomized, placebo-controlled, academic, double-blind superior trial. Discussion This is the first report on a selenium randomized trial in bladder cancer patients. Trial registration ClinicalTrials.gov identifier: NCT00729287

  6. Neoadjuvant chemotherapy for invasive bladder cancer.

    Science.gov (United States)

    Sonpavde, Guru; Sternberg, Cora N

    2012-04-01

    Neoadjuvant cisplatin-based combination chemotherapy is an established standard for resectable muscle-invasive bladder cancer, a disease with a pattern of predominantly distant and early recurrences. Pathologic complete remission appears to be an intermediate surrogate for survival when employing combination chemotherapy. Moreover, baseline host and tumor tissue studies may enable the discovery of biomarkers predictive of activity. The neoadjuvant setting also provides a window of opportunity to evaluate novel biologic agents or rational combinations of biologic agents to obtain a signal of biologic activity. The residual tumor after neoadjuvant therapy may be exploited to study the mechanism of action and resistance. Cisplatin-ineligible patients warrant the evaluation of tolerable neoadjuvant regimens. Given that bladder cancer is characterized by initial localized presentation in the vast majority of cases, the paradigm of neoadjuvant therapy may expedite the development of novel systemic agents.

  7. Urinary bladder cancer in dogs, a naturally occurring model for cancer biology and drug development.

    Science.gov (United States)

    Knapp, Deborah W; Ramos-Vara, José A; Moore, George E; Dhawan, Deepika; Bonney, Patty L; Young, Kirsten E

    2014-01-01

    Each year more than 65,000 people are diagnosed with urinary bladder cancer, and more than 14,000 people die from the disease in the United States. Studies in relevant animal models are essential to improve the management of bladder cancer. Naturally occurring bladder cancer in dogs very closely mimics human invasive bladder cancer, specifically high-grade invasive transitional cell carcinoma (TCC; also referred to as invasive urothelial carcinoma) in cellular and molecular features; biological behavior, including sites and frequency of metastasis; and response to therapy. Canine bladder cancer complements experimentally induced rodent tumors in regard to animal models of bladder cancer. Results of cellular and molecular studies and -omics analyses in dogs are expected to lead to improved detection of TCC and preneoplastic lesions, earlier intervention, better prediction of patient outcome, and more effective TCC management overall. Studies in dogs are being used to help define heritable risks (through very strong breed-associated risk) and environment risks and to evaluate prevention and treatment approaches that benefit humans as well as dogs. Clinical treatment trials in pet dogs with TCC are considered a win-win scenario by clinician scientists and pet owners. The individual dog benefits from effective treatment, the results are expected to help other dogs, and the findings are expected to ultimately help humans with TCC. This article provides an overview of canine TCC, a summary of the similarities and differences between canine and human invasive TCC, and examples of the types of valuable translational research that can be done using dogs with naturally occurring TCC.

  8. One case treated bladder cancer with Immunity-herbal acupuncture

    Directory of Open Access Journals (Sweden)

    Dong-Suk Kim

    2002-02-01

    Full Text Available In oriental medicine bladder cancer had been called '溺血(Hematuria', 血淋(Blood Stranguria', 濕熱河注(Downward Flow of Damp-heat' and so on. The symptoms are Hematuria, Oliguria, Lower abdomen pain, febrile sensation and Anemia etc. These are similar to the symptoms of bladder cancer by modem medicine. I have experienced a bladder cancer patient who was diagnosed as stage Ⅲ. She has been treated bladder cancer with Immunity herbal acupuncture and Her clinical and objective symptoms have been better. Therefore I report this results.

  9. One case treated bladder cancer with Immunity-herbal acupuncture

    OpenAIRE

    2002-01-01

    In oriental medicine bladder cancer had been called '溺血(Hematuria)', 血淋(Blood Stranguria)', 濕熱河注(Downward Flow of Damp-heat)' and so on. The symptoms are Hematuria, Oliguria, Lower abdomen pain, febrile sensation and Anemia etc. These are similar to the symptoms of bladder cancer by modem medicine. I have experienced a bladder cancer patient who was diagnosed as stage Ⅲ. She has been treated bladder cancer with Immunity herbal acupuncture and Her clinical and objective symptoms have been bett...

  10. [Bladder cancer at an early age in father and son].

    Science.gov (United States)

    Ovsiannikov, D; Stöhr, R; Hartmann, A; Böttrich, R; Hengstler, J G; Golka, K

    2011-12-01

    Bladder cancer may be caused by external factors like tobacco smoking, but may also be familial. We report on a father and son who developed this tumour at the ages of 45 and 35. Testing various genetic markers including the mismatch repair proteins MLH1, MSH2 and MSH6, whose loss is associated with a higher risk for hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome), did not point to a familial disease. Thus the heavy smoking habits of the two patients must be considered as causal.

  11. Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry.

    Science.gov (United States)

    Figueroa, Jonine D; Middlebrooks, Candace D; Banday, A Rouf; Ye, Yuanqing; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Koutros, Stella; Kiemeney, Lambertus A; Rafnar, Thorunn; Bishop, Timothy; Furberg, Helena; Matullo, Giuseppe; Golka, Klaus; Gago-Dominguez, Manuela; Taylor, Jack A; Fletcher, Tony; Siddiq, Afshan; Cortessis, Victoria K; Kooperberg, Charles; Cussenot, Olivier; Benhamou, Simone; Prescott, Jennifer; Porru, Stefano; Dinney, Colin P; Malats, Núria; Baris, Dalsu; Purdue, Mark P; Jacobs, Eric J; Albanes, Demetrius; Wang, Zhaoming; Chung, Charles C; Vermeulen, Sita H; Aben, Katja K; Galesloot, Tessel E; Thorleifsson, Gudmar; Sulem, Patrick; Stefansson, Kari; Kiltie, Anne E; Harland, Mark; Teo, Mark; Offit, Kenneth; Vijai, Joseph; Bajorin, Dean; Kopp, Ryan; Fiorito, Giovanni; Guarrera, Simonetta; Sacerdote, Carlotta; Selinski, Silvia; Hengstler, Jan G; Gerullis, Holger; Ovsiannikov, Daniel; Blaszkewicz, Meinolf; Castelao, Jose Esteban; Calaza, Manuel; Martinez, Maria Elena; Cordeiro, Patricia; Xu, Zongli; Panduri, Vijayalakshmi; Kumar, Rajiv; Gurzau, Eugene; Koppova, Kvetoslava; Bueno-De-Mesquita, H Bas; Ljungberg, Börje; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth C; Tjønneland, Anne; Brennan, Paul; Chang-Claude, Jenny; Riboli, Elio; Conti, David; Stern, Marianna C; Pike, Malcolm C; Van Den Berg, David; Yuan, Jian-Min; Hohensee, Chancellor; Jeppson, Rebecca P; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Turman, Constance; De Vivo, Immaculata; Giovannucci, Edward; Hunter, David J; Kraft, Peter; Lindstrom, Sara; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Kamat, Ashish M; Zhang, Liren; Gong, Yilei; Pu, Xia; Hutchinson, Amy; Burdett, Laurie; Wheeler, William A; Karagas, Margaret R; Johnson, Alison; Schned, Alan; Monawar Hosain, G M; Schwenn, Molly; Kogevinas, Manolis; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Andriole, Gerald; Grubb, Robert; Black, Amanda; Diver, W Ryan; Gapstur, Susan M; Weinstein, Stephanie; Virtamo, Jarmo; Haiman, Christopher A; Landi, Maria Teresa; Caporaso, Neil E; Fraumeni, Joseph F; Vineis, Paolo; Wu, Xifeng; Chanock, Stephen J; Silverman, Debra T; Prokunina-Olsson, Ludmila; Rothman, Nathaniel

    2016-03-15

    Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer.

  12. Frequent somatic CDH1 loss-of-function mutations in plasmacytoid variant bladder cancer.

    Science.gov (United States)

    Al-Ahmadie, Hikmat A; Iyer, Gopa; Lee, Byron H; Scott, Sasinya N; Mehra, Rohit; Bagrodia, Aditya; Jordan, Emmet J; Gao, Sizhi Paul; Ramirez, Ricardo; Cha, Eugene K; Desai, Neil B; Zabor, Emily C; Ostrovnaya, Irina; Gopalan, Anuradha; Chen, Ying-Bei; Fine, Samson W; Tickoo, Satish K; Gandhi, Anupama; Hreiki, Joseph; Viale, Agnès; Arcila, Maria E; Dalbagni, Guido; Rosenberg, Jonathan E; Bochner, Bernard H; Bajorin, Dean F; Berger, Michael F; Reuter, Victor E; Taylor, Barry S; Solit, David B

    2016-04-01

    Plasmacytoid bladder cancer is an aggressive histologic variant with a high risk of disease-specific mortality. Using whole-exome and targeted sequencing, we find that truncating somatic alterations in the CDH1 gene occur in 84% of plasmacytoid carcinomas and are specific to this histologic variant. Consistent with the aggressive clinical behavior of plasmacytoid carcinomas, which frequently recur locally, CRISPR/Cas9-mediated knockout of CDH1 in bladder cancer cells enhanced cell migration.

  13. Preoperative irradiation and cystectomy for bladder cancer.

    Science.gov (United States)

    Smith, J A; Batata, M; Grabstald, H; Sogani, P C; Herr, H; Whitmore, W F

    1982-03-01

    Between 1971 and 1974, 101 patients at Memorial Sloan-Kettering Cancer Center underwent planned integrated treatment for bladder cancer with 2000 rads by megavoltage delivered to the whole pelvis over five consecutive days followed by radical cystectomy within a week. The overall five-year survival rate was 39%; the hospital mortality rate was 2%. In the pelvis alone tumor recurred in 9% of the patients. These results support other studies demonstrating the efficacy of this and other regimens of preoperative irradiation and cystectomy.

  14. The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease.

    Science.gov (United States)

    Fu, Yi-Ping; Kohaar, Indu; Moore, Lee E; Lenz, Petra; Figueroa, Jonine D; Tang, Wei; Porter-Gill, Patricia; Chatterjee, Nilanjan; Scott-Johnson, Alexandra; Garcia-Closas, Montserrat; Muchmore, Brian; Baris, Dalsu; Paquin, Ashley; Ylaya, Kris; Schwenn, Molly; Apolo, Andrea B; Karagas, Margaret R; Tarway, McAnthony; Johnson, Alison; Mumy, Adam; Schned, Alan; Guedez, Liliana; Jones, Michael A; Kida, Masatoshi; Hosain, G M Monawar; Malats, Nuria; Kogevinas, Manolis; Tardon, Adonina; Serra, Consol; Carrato, Alfredo; Garcia-Closas, Reina; Lloreta, Josep; Wu, Xifeng; Purdue, Mark; Andriole, Gerald L; Grubb, Robert L; Black, Amanda; Landi, Maria T; Caporaso, Neil E; Vineis, Paolo; Siddiq, Afshan; Bueno-de-Mesquita, H Bas; Trichopoulos, Dimitrios; Ljungberg, Börje; Severi, Gianluca; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth C; Tjønneland, Anne; Brennan, Paul; Chang-Claude, Jenny; Riboli, Elio; Prescott, Jennifer; Chen, Constance; De Vivo, Immaculata; Govannucci, Edward; Hunter, David; Kraft, Peter; Lindstrom, Sara; Gapstur, Susan M; Jacobs, Eric J; Diver, W Ryan; Albanes, Demetrius; Weinstein, Stephanie J; Virtamo, Jarmo; Kooperberg, Charles; Hohensee, Chancellor; Rodabough, Rebecca J; Cortessis, Victoria K; Conti, David V; Gago-Dominguez, Manuela; Stern, Mariana C; Pike, Malcolm C; Van Den Berg, David; Yuan, Jian-Min; Haiman, Christopher A; Cussenot, Olivier; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Porru, Stefano; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Grossman, H Barton; Wang, Zhaoming; Deng, Xiang; Chung, Charles C; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Fraumeni, Joseph; Chanock, Stephen J; Hewitt, Stephen M; Silverman, Debra T; Rothman, Nathaniel; Prokunina-Olsson, Ludmila

    2014-10-15

    A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) ≥ 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 × 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (P(trend) = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models.

  15. The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease

    Science.gov (United States)

    Fu, Yi-Ping; Kohaar, Indu; Moore, Lee E.; Lenz, Petra; Figueroa, Jonine D.; Tang, Wei; Porter-Gill, Patricia; Chatterjee, Nilanjan; Scott-Johnson, Alexandra; Garcia-Closas, Montserrat; Muchmore, Brian; Baris, Dalsu; Paquin, Ashley; Ylaya, Kris; Schwenn, Molly; Apolo, Andrea B.; Karagas, Margaret R.; Tarway, McAnthony; Johnson, Alison; Mumy, Adam; Schned, Alan; Guedez, Liliana; Jones, Michael A.; Kida, Masatoshi; Monawar Hosain, GM; Malats, Nuria; Kogevinas, Manolis; Tardon, Adonina; Serra, Consol; Carrato, Alfredo; Garcia-Closas, Reina; Lloreta, Josep; Wu, Xifeng; Purdue, Mark; Andriole, Gerald L.; Grubb, Robert L.; Black, Amanda; Landi, Maria T.; Caporaso, Neil E.; Vineis, Paolo; Siddiq, Afshan; Bueno-de-Mesquita, H. Bas; Trichopoulos, Dimitrios; Ljungberg, Börje; Severi, Gianluca; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth C.; Tjønneland, Anne; Brennan, Paul; Chang-Claude, Jenny; Riboli, Elio; Prescott, Jennifer; Chen, Constance; De Vivo, Immaculata; Govannucci, Edward; Hunter, David; Kraft, Peter; Lindstrom, Sara; Gapstur, Susan M.; Jacobs, Eric J.; Diver, W. Ryan; Albanes, Demetrius; Weinstein, Stephanie J.; Virtamo, Jarmo; Kooperberg, Charles; Hohensee, Chancellor; Rodabough, Rebecca J.; Cortessis, Victoria K.; Conti, David V.; Gago-Dominguez, Manuela; Stern, Mariana C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Haiman, Christopher A.; Cussenot, Olivier; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Porru, Stefano; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Grossman, H. Barton; Wang, Zhaoming; Deng, Xiang; Chung, Charles C.; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Fraumeni, Joseph; Chanock, Stephen J.; Hewitt, Stephen M.; Silverman, Debra T.; Rothman, Nathaniel; Prokunina-Olsson, Ludmila

    2014-01-01

    A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell cycle protein. We performed genetic fine mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r2≥0.7) associated with increased bladder cancer risk. From this group we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWAS, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele odds ratio (OR) =1.18 (95%CI=1.09-1.27, p=4.67×10−5 vs. OR =1.01 (95%CI=0.93-1.10, p=0.79) for non-aggressive disease, with p=0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (p=0.013) and, independently, with each rs7257330-A risk allele (ptrend=0.024). Over-expression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E over-expression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models. PMID:25320178

  16. Case-control study of bladder cancer in New Jersey. I. Occupational exposures in white males.

    Science.gov (United States)

    Schoenberg, J B; Stemhagen, A; Mogielnicki, A P; Altman, R; Abe, T; Mason, T J

    1984-05-01

    The occupational bladder cancer risk for New Jersey white males was estimated with the use of both industry-job title-based and exposure-based analyses of data from 658 incident cases and 1,258 general population controls. The overall bladder cancer risk attributable to occupational exposures was estimated as 20-22%. A wide variety of employment categories and exposures contributed to this risk. Odds ratios were significantly high for employment as garage and gas station workers and food counter workers and/or cooks and for exposure to leather, rubber, paint, printing ink, and other organic compounds. Odds ratios for textile mill workers, chemical workers, and metal workers for the a priori high-risk employment category and odds ratios for those exposed to dyes, chlorinated compounds, and rubber showed significant differences between younger and older subjects. Bladder cancer risk associated with occupational exposures was not limited to persons with initial exposures before 25 years of age. However, there was significantly decreasing risk for bladder cancer with increasing age at first exposure for chemical workers and metal workers and for the a priori high-risk materials and metals. Drivers and/or deliverymen and miscellaneous laborers had significantly increasing bladder cancer risk with increasing duration of employment.

  17. General Information about Bladder Cancer

    Science.gov (United States)

    ... from a well that has high levels of arsenic . Drinking water that has been treated with chlorine . ... of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative ...

  18. Dogs Sniff out Bladder Cancer

    Institute of Scientific and Technical Information of China (English)

    Helen Pearson; 秦阳阳

    2004-01-01

    @@ Dogs have always taken an inordinate① interest in urine. But now UK researchers have put that penchant② to good use, and shown that the animals can detect signs of bladder③ cancer in human pee④.

  19. The health economics of bladder cancer: an updated review of the published literature.

    Science.gov (United States)

    Yeung, Christina; Dinh, Tuan; Lee, Joseph

    2014-11-01

    The purpose of this paper is to provide a current view of the economic burden of bladder cancer, with a focus on the cost effectiveness of available interventions. This review updates a previous systematic review and includes 72 new papers published between 2000 and 2013. Bladder cancer continues to be one of the most common and expensive malignancies. The annual cost of bladder cancer in the USA during 2010 was $US4 billion and is expected to rise to $US5 billion by 2020. Ten years ago, urinary markers held the potential to lower treatment costs of bladder cancer. However, subsequent real-world experiments have demonstrated that further work is necessary to identify situations in which these technologies can be applied in a cost-effective manner. Adjunct cytology remains a part of diagnostic standard of care, but recent research suggests that it is not cost effective due to its low diagnostic yield. Analysis of intravesical chemotherapy after transurethral resection of bladder tumor (TURBT), neo-adjuvant therapy for cystectomy, and robot-assisted laparoscopic cystectomy suggests that these technologies are cost effective and should be implemented more widely for appropriate patients. The existing literature on the cost effectiveness of bladder cancer treatments has improved substantially since 2000. The body of work now includes many new models, registry analyses, and real-world studies. However, there is still a need for new implementation guidelines, new risk modeling tools, and a better understanding of the empirical burden of bladder cancer.

  20. Oncolytic Viruses in the Treatment of Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Kyle G. Potts

    2012-01-01

    Full Text Available Bladder carcinoma is the second most common malignancy of the urinary tract. Up to 85% of patients with bladder cancer are diagnosed with a tumor that is limited to the bladder mucosa (Ta, T1, and CIS. These stages are commonly termed as non-muscle-invasive bladder cancer (NMIBC. Although the treatment of NMIBC has greatly improved in recent years, there is a need for additional therapies when patients fail bacillus Calmette-Guérin (BCG and chemotherapeutic agents. We propose that bladder cancer may be an ideal target for oncolytic viruses engineered to selectively replicate in and lyse tumor cells leaving normal cells unharmed. In support of this hypothesis, here we review current treatment strategies for bladder cancer and their shortcomings, as well as recent advancements in oncolytic viral therapy demonstrating encouraging safety profiles and antitumor activity.

  1. THE STUDY OF MICROSATELLITES ALTERATION IN DIAGNOSES OF BLADDER CANCER

    Institute of Scientific and Technical Information of China (English)

    Zhao Jun; He Dalin; Yang Lin; He Hui; Nan Xunyi

    2006-01-01

    Objective To investigate the possibility of microsatellite alteration (MA) in diagnosis of bladder cancer of Chinese people, and find the better panel which will be used in clinic. Methods A total of 6 and 10microsatellite markers were chosen, PCR-SSLP silver staining assay was performed in 31 and 32 bladder cancers tissue,exfoliate cells in urine and 10, 15 non-bladder cancers exfoliate cells in urine, respectively. Results MA (+) was found in 28 out of 31, 30 out of 32 bladder cancers, and the sensitivity was 90.3%, 93.7% respectively. The MA of urine sediment of 25 non-bladder cancers was negative, and the specificity was 100%. The cytology was carried out among 19 out of 31, 20 out of 32 bladder cancers at the same time, 2 cases ( 10.3 %) and 3 cases ( 15 % ) were found cancer positive, and the sensitivity is significantly lower than that by the analysis of MA in exfoliated cells. Conclusion MA was not associated with grade and stage of the bladder cancer. MA assay is a sensitive and effective method for the early detection of bladder cancer and post-operation surveillance.

  2. URINARY BLADDER CANCER WITH FOCUS ON OCCUPATIONAL DYE WORKERS

    Directory of Open Access Journals (Sweden)

    K.Revathi

    2015-11-01

    Full Text Available Benzidine based azo dyes are proven carcinogens, mutagens and have been linked to bladder cancer of human beings and laboratory animals. The textile and dyestuff manufacturing industry are the two major sources for releasing of azo dyes. Various research groups have started work on genotoxic effect of textile dyes in occupational workers of textile dye industry. Bladder cancer is the most common form of cancer in dye industries. Most of people between age 50 and 70 group of are diagnosed with bladder cancer. Men are more likely than the women to develop bladder cancer. Bladder cancer is a disease in which abnormal cells multiply without control in the bladder. The most common type of bladder cancer begins in cells lining the inside of the bladder and is called transitional cell carcinoma. Tumor markers are substances that can be found in the body when cancer is present. They are most often found in the blood or urine. The review deals about the impacts of the industry dyes on human health.

  3. Urovysion™ testing can lead to early identification of intravesical therapy failure in patients with high risk non-muscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Jared M. Whitson

    2009-12-01

    Full Text Available Purpose: In this study, we investigated the ability of UroVysion™ to assess response to intravesical therapy in patients with high risk superficial bladder tumors. Materials and methods: We performed a retrospective review of patients undergoing intravesical therapy for high risk superficial bladder tumors. Urine specimens were collected for UroVysion™ analysis before and immediately after a course of intravesical therapy. Cytology and cystoscopy were performed six weeks after treatment, using either a positive cytology or visible abnormality on cystoscopy as a prompt for biopsy. The operating characteristics of the UroVysion™ test were then determined. Results: 41 patients were identified in whom 47 cycles of induction and 41 cycles of maintenance intravesical therapy were given during the study period. This yielded a total of 88 treatment and evaluation cycles. Median follow-up was 9 months per induction (range 1-21 months and 13 months per patient (range 1-25 months. A total of 133 urine samples were collected for UroVysion™ of which 40 were positive. Based upon standard clinical evaluation, 41 biopsies were performed which detected 20 recurrences. UroVysion™ testing performed immediately upon completion of therapy for the 41 patients undergoing biopsy yielded a sensitivity, specificity, and accuracy of 85%, 61%, and 71%. Conclusions: The use of UroVysion™ following intravesical therapy for high-risk superficial bladder tumors helps to identify patients at high risk of refractory or recurrent disease who should undergo immediate biopsy under anesthesia.

  4. Studies on the relation between bladder cancer and benzidine or its derived dyes in Shanghai.

    Science.gov (United States)

    You, X Y; Chen, J G; Hu, Y N

    1990-08-01

    Shanghai is the largest industrial centre in China and has a history of about 50 years in producing and applying benzidine derived dyes. A series of epidemiological studies on the carcinogenicity of benzidine and its derived dyes have been performed since 1979. This report describes three such studies. A case-control study was carried out on 344 cases of bladder cancer, each matched for age and sex, with a person without bladder cancer. Factors studied were occupational exposure, smoking, drinking, medical histories, and family history of bladder cancer and other carcinomas. The correlation between bladder cancer and occupational exposures (relative risk (RR) 5.71) was greater than that between bladder cancer and smoking (RR 1.53). A retrospective cohort study was conducted in seven dyestuffs factories where benzidine had served as an intermediate in the manufacture of dyes before 1976. The cohort was made up of 550 men and 186 women. The men were divided into two groups according to job; 354 were assigned to a presynthesis group and 196 to a postsynthesis group. Those in the presynthesis group were thought to have been exposed to benzidine and the subjects in the postsynthesis group were exposed mainly to its derived dyes. The 15 cases of bladder cancer diagnosed were all in the presynthesis group, although an excess of bladder cancer was also seen in the whole cohort. The standardised incidence ratio (SIR) of bladder cancer was 1918 in the whole cohort and 3500 in the presynthesis group. Moreover, the SIR of bladder cancer in a subgroup working directly with the assignment, transport, and mixing of benzidine was as high as 7500. A further retrospective cohort study was made on incidence of cancer among 1420 workers who used benzidine derived dyes in 43 textile printing and dyeing factories. No excess carcinoma was found. These results suggest that, in Shanghai, the main cause of bladder cancer is occupational exposure, especially to benzidine. The risk of bladder

  5. Tyrosine kinase ETK/BMX is up-regulated in bladder cancer and predicts poor prognosis in patients with cystectomy.

    Science.gov (United States)

    Guo, Shengjie; Sun, Feng; Guo, Zhiyong; Li, Wei; Alfano, Alan; Chen, Hegang; Magyar, Clara E; Huang, Jiaoti; Chai, Toby C; Qiu, Shaopeng; Qiu, Yun

    2011-03-07

    Deregulation of the non-receptor tyrosine kinase ETK/BMX has been reported in several solid tumors. In this report, we demonstrated that ETK expression is progressively increased during bladder cancer progression. We found that down-regulation of ETK in bladder cancer cells attenuated STAT3 and AKT activity whereas exogenous overexpression of ETK had opposite effects, suggesting that deregulation of ETK may attribute to the elevated activity of STAT3 and AKT frequently detected in bladder cancer. The survival, migration and invasion of bladder cancer cells were significantly compromised when ETK expression was knocked down by a specific shRNA. In addition, we showed that ETK localizes to mitochondria in bladder cancer cells through interacting with Bcl-XL and regulating ROS production and drug sensitivity. Therefore, ETK may play an important role in regulating survival, migration and invasion by modulating multiple signaling pathways in bladder cancer cells. Immunohistochemistry analysis on tissue microarrays containing 619 human bladder tissue samples shows that ETK is significantly upregulated during bladder cancer development and progression and ETK expression level predicts the survival rate of patients with cystectomy. Taken together, our results suggest that ETK may potentially serve as a new drug target for bladder cancer treatment as well as a biomarker which could be used to identify patients with higher mortality risk, who may be benefited from therapeutics targeting ETK activity.

  6. Tyrosine kinase ETK/BMX is up-regulated in bladder cancer and predicts poor prognosis in patients with cystectomy.

    Directory of Open Access Journals (Sweden)

    Shengjie Guo

    Full Text Available Deregulation of the non-receptor tyrosine kinase ETK/BMX has been reported in several solid tumors. In this report, we demonstrated that ETK expression is progressively increased during bladder cancer progression. We found that down-regulation of ETK in bladder cancer cells attenuated STAT3 and AKT activity whereas exogenous overexpression of ETK had opposite effects, suggesting that deregulation of ETK may attribute to the elevated activity of STAT3 and AKT frequently detected in bladder cancer. The survival, migration and invasion of bladder cancer cells were significantly compromised when ETK expression was knocked down by a specific shRNA. In addition, we showed that ETK localizes to mitochondria in bladder cancer cells through interacting with Bcl-XL and regulating ROS production and drug sensitivity. Therefore, ETK may play an important role in regulating survival, migration and invasion by modulating multiple signaling pathways in bladder cancer cells. Immunohistochemistry analysis on tissue microarrays containing 619 human bladder tissue samples shows that ETK is significantly upregulated during bladder cancer development and progression and ETK expression level predicts the survival rate of patients with cystectomy. Taken together, our results suggest that ETK may potentially serve as a new drug target for bladder cancer treatment as well as a biomarker which could be used to identify patients with higher mortality risk, who may be benefited from therapeutics targeting ETK activity.

  7. IMMUNOHISTOCHEMICAL ANALYSIS OF UROTHELIAL BLADDER CANCERS

    Directory of Open Access Journals (Sweden)

    Katarina Bevizova

    2013-01-01

    Full Text Available Malignant cancers of urinary bladder are the second most common malignancy of the urinary tract and the fourth most common malignancy in general, especially in men. The aim of this study was a retrospective analysis of selected markers (p53, Ki-67 and E-cadherin of urinary bladder cancers from the Department of Urology in Bratislava, Slovak Republic between years 2007 and 2009. We analysed 244 patients (202 males, 42 females with diagnosed bladder cancer via cystoscopy and subsequent transurethral resection. Patients’ age varied from 36 to 98 years. Obtained samples were fixed by 10% buffered formalin for 24 to 48 h. Subsequently, they were dehydrated in ascending ethanol series and embedded in paraffin. The parafin sections of 5 µm were prepared by microtome and they were stained by haematoxylin and eosin. The antibodies against to p53, Ki-67 and E-cadherin were used in immunohistochemical analysis. Statistical evaluation was performed via SPSS using non-parametric Kruskal-Wallis test and p values<0.05 were considered statistically significant. No significant differences in the expression of selected markers were found between genders. Expression of p53 and Ki-67, in G1 and G2 of low grade tumours was lower in comparison to their expression in G3 tumors. Expression of E-cadherin was the opposite in this case. The expression of p53 and Ki-67 positively correlated with tumor’s depth of invasion, while the expression of E-cadherin significantly decreased. In case of T4 tumors, the expression of all markers exhibited consistently high values. When analysing tumor multiplicity, the expression of p53 and Ki-67 significantly decreased, while the expression of E-cadherin significantly increased. Based on the obtained results it can be concluded that the analysis of p53, Ki-67 and E-cadherin expression is essential for diagnostics and prognostics of bladder cancer and should be routinely used in daily practise together with

  8. Bladder Cancer Immunotherapy: BCG and Beyond

    Directory of Open Access Journals (Sweden)

    Eric J. Askeland

    2012-01-01

    Full Text Available Mycobacterium bovis bacillus Calmette-Guérin (BCG has become the predominant conservative treatment for nonmuscle invasive bladder cancer. Its mechanism of action continues to be defined but has been shown to involve a T helper type 1 (Th1 immunomodulatory response. While BCG treatment is the current standard of care, a significant proportion of patients fails or do not tolerate treatment. Therefore, many efforts have been made to identify other intravesical and immunomodulating therapeutics to use alone or in conjunction with BCG. This paper reviews the progress of basic science and clinical experience with several immunotherapeutic agents including IFN-α, IL-2, IL-12, and IL-10.

  9. Bladder Cancer Immunotherapy: BCG and Beyond.

    Science.gov (United States)

    Askeland, Eric J; Newton, Mark R; O'Donnell, Michael A; Luo, Yi

    2012-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) has become the predominant conservative treatment for nonmuscle invasive bladder cancer. Its mechanism of action continues to be defined but has been shown to involve a T helper type 1 (Th1) immunomodulatory response. While BCG treatment is the current standard of care, a significant proportion of patients fails or do not tolerate treatment. Therefore, many efforts have been made to identify other intravesical and immunomodulating therapeutics to use alone or in conjunction with BCG. This paper reviews the progress of basic science and clinical experience with several immunotherapeutic agents including IFN-α, IL-2, IL-12, and IL-10.

  10. Glutathione S-transferase P1 ILE105Val polymorphism in occupationally exposed bladder cancer cases.

    Science.gov (United States)

    Kopps, Silke; Angeli-Greaves, Miriam; Blaszkewicz, Meinolf; Prager, Hans-Martin; Roemer, Hermann C; Lohlein, Dietrich; Weistenhofer, Wobbeke; Bolt, Hermann M; Golka, Klaus

    2008-01-01

    The genotype glutathione S-transferase P1 (GSTP1) influences the risk for bladder cancer among Chinese workers occupationally exposed to benzidine. Studies of Caucasian bladder cancer cases without known occupational exposures showed conflicting results. Research was thus conducted to define the role of GSTP1 genotypes in Caucasian bladder cancer cases with an occupational history of exposure to aromatic amines. DNA from 143 cases reported to the Industrial Professional Associations (Berufsgenossenschaften) in Germany from 1996 to 2004, who had contracted urothelial cancer due to occupational exposure, and 196 patients from one Department of Surgery in Dortmund, without known malignancy in their medical history, were genotyped using real-time polymerase chain reaction (PCR) (LightCycler) in relation to GSTP1 A1578G (Ile105Val) polymorphism. Among the subjects with bladder cancer, 46% presented the AA genotype, 39% the AG genotype, and 15% the GG genotype. In the surgical (noncancer) control group analyzed, 42% presented the AA genotype, 42% the AG genotype, and 16% the GG genotype. A subgroup of bladder cancer cases, represented by 46 painters, showed a distribution of 41% of the AA genotype, 48% of the AG genotype, and 11% of the GG genotype. Data indicated that in Caucasians exposed to aromatic amines the GSTP1 A1578G polymorphism did not appear to play a significant role as a predisposing factor for bladder cancer incidence.

  11. The impact of pioglitazone on bladder cancer and cardiovascular events.

    Science.gov (United States)

    Lee, Esther J; Marcy, Todd R

    2014-08-01

    Type 2 diabetes mellitus (T2DM) is a chronic condition with increasing prevalence and severe complications. Thiazolidinediones have been marketed since 1997 and are effective glucose-lowering drugs, but individual drugs within the class have been linked to serious adverse effects that resulted in the removal of troglitazone from the market, restrictions to rosiglitazone's use, and a warning added to pioglitazone's label. In 2007, a meta-analysis linked rosiglitazone to myocardial infarction (MI). Pioglitazone does not appear to share this risk. To the contrary, pioglitazone may reduce risk for MI. However, retrospective evaluations have increasingly linked pioglitazone to a higher risk of bladder cancer that appears to be time- and dose-dependent. Pioglitazone remains a medication appropriate for consideration in the management of T2DM; however, clinicians and patients should weigh its risks compared with alternatives, with a regular review of risks.

  12. Antibody conjugate radioimmunotherapy of superficial bladder cancer

    Directory of Open Access Journals (Sweden)

    Alan Perkins

    2002-09-01

    Full Text Available The administration of antibody conjugates for cancer therapy is now proving to be of clinical value. We are currently undertaking a programme of clinical studies using the monoclonal antibody C595 (IgG3 which reacts with the MUC1 glycoprotein antigen that is aberrantly expressed in a high proportion of bladder tumours. Radioimmunoconjugates of the C595 antibody have been produced with high radiolabelling efficiency and immunoreactivity using Tc-99m and In-111 for diagnostic imaging, and disease staging and the cytotoxic radionuclides Cu-67 and Re-188 for therapy of superficial bladder cancer. A Phase I/II therapeutic trail involving the intravesical administration of antibody directly into the bladder has now begun.A administração de anticorpos conjugados para o tratamento do câncer está agora provando ser de valor clínico. Nós estamos atualmente realizando um programa de estudos clínicos usando o anticorpo monoclonal C595 (IgG3 que reage com a glicoproteína MUC1 que está aberrantemente expressa numa alta proporção de tumores de bexiga. Tem sido produzidos radioimunoconjugados do anticorpo C595, com alta eficiência de radiomarcação e a imunoreatividade, usando-se o Tc-99m e In-111, para o diagnóstico por imagem e estagiamento de doenças. Tem sido produzidos, também, radionuclídeos citotóxicos (Cu-67 e Re-188 para o tratamento de cânceres superficiais de bexiga. A fase terapêutica I/II já se iniciou, envolvendo a administração intravesical do anticorpo diretamente na bexiga.

  13. Efficient intravesical therapy of bladder cancer with cationic doxorubicin nanoassemblies.

    Science.gov (United States)

    Jin, Xun; Zhang, Peilan; Luo, Li; Cheng, Hao; Li, Yunzu; Du, Ting; Zou, Bingwen; Gou, Maling

    Nanoparticles have promising applications in drug delivery for cancer therapy. Herein, we prepared cationic 1,2-dioleoyl-3-trimethylammonium propane/methoxypoly (ethyleneglycol) (DPP) nanoparticles to deliver doxorubicin (Dox) for intravesical therapy of bladder cancer. The DPP micelles have a mean dynamic diameter of 18.65 nm and a mean zeta potential of +19.6 mV. The DPP micelles could prolong the residence of Dox in the bladder, enhance the penetration of Dox into the bladder wall, and improve cellular uptake of Dox. The encapsulation by DPP micelles significantly improved the anticancer effect of Dox against orthotopic bladder cancer in vivo. This work described a Dox-loaded DPP nanoparticle with potential applications in intravesical therapy of bladder cancer.

  14. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Frolich, Camilla; Albrechtsen, Reidar; Andersen, Lars Dyrskjøt

    2006-01-01

    PURPOSE: We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. EXPERIMENTAL DESIGN: ADAM12...... gene expression was evaluated in tumors from 96 patients with bladder cancer using a customized Affymetrix GeneChip. Gene expression in bladder cancer was validated using reverse transcription-PCR, quantitative PCR, and in situ hybridization. Protein expression was evaluated by immunohistochemical...

  15. The effect of tobacco, XPC, ERCC2 and ERCC5 genetic variants in bladder cancer development

    Directory of Open Access Journals (Sweden)

    Othman Fethi

    2011-03-01

    Full Text Available Abstract Background In this work, we have conducted a case-control study in order to assess the effect of tobacco and three genetic polymorphisms in XPC, ERCC2 and ERCC5 genes (rs2228001, rs13181 and rs17655 in bladder cancer development in Tunisia. We have also tried to evaluate whether these variants affect the bladder tumor stage and grade. Methods The patients group was constituted of 193 newly diagnosed cases of bladder tumors. The controls group was constituted of non-related healthy subjects. The rs2228001, rs13181 and rs17655 polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism technique. Results Our data have reported that non smoker and light smoker patients (1-19PY are protected against bladder cancer development. Moreover, light smokers have less risk for developing advanced tumors stage. When we investigated the effect of genetic polymorphisms in bladder cancer development we have found that ERCC2 and ERCC5 variants were not implicated in the bladder cancer occurrence. However, the mutated homozygous genotype for XPC gene was associated with 2.09-fold increased risk of developing bladder cancer compared to the control carrying the wild genotype (p = 0.03, OR = 2.09, CI 95% 1.09-3.99. Finally, we have found that the XPC, ERCC2 and ERCC5 variants don't affect the tumors stage and grade. Conclusion These results suggest that the mutated homozygous genotype for XPC gene was associated with increased risk of developing bladder. However we have found no association between rs2228001, rs13181 and rs17655 polymorphisms and tumors stage and grade.

  16. Recent advances in the diagnosis and treatment of bladder cancer

    Directory of Open Access Journals (Sweden)

    Cheung Grace

    2013-01-01

    Full Text Available Abstract Bladder cancer is the commonest malignancy of the urinary tract. In this review, we look at the latest developments in the diagnosis and management of this condition. Cystoscopy and urine cytology are the most important tools in the diagnosis and follow-up of bladder cancer. Various alternatives have been investigated, either to reduce the frequency of cystoscopy, or improve its sensitivity for detection of tumors. These include urine-based markers and point-of-care tests. Narrow-band imaging and photodynamic diagnosis/blue-light cystoscopy have shown promise in improving detection and reducing recurrence of bladder tumors, by improving the completion of bladder resection when compared with standard resection in white light. The majority of patients with a new diagnosis of bladder cancer have non-muscle-invasive bladder cancer, which requires adjuvant intravesical chemotherapy and/or immunotherapy. Recent developments in post-resection intravesical regimens are discussed. For patients with muscle-invasive bladder cancer, both laparoscopic radical cystectomy and robot-assisted radical cystectomy have been shown to reduce peri-operative morbidity, while being oncologically equivalent to open radical cystectomy in the medium term. Bladder-preserving strategies entail resection and chemoradiation, and in selected patients give equivalent results to surgery. The development, advantages, and disadvantages of these newer approaches are also discussed.

  17. Photodynamic diagnosis of bladder cancer in ex vivo urine cytology

    Science.gov (United States)

    Fu, C. Y.; Ng, B. K.; Razul, S. Gulam; Olivo, Malini C.; Lau, Weber K. O.; Tan, P. H.; Chin, William

    2006-02-01

    Bladder cancer is the fourth common malignant disease worldwide, accounting for 4% of all cancer cases. In Singapore, it is the ninth most common form of cancer. The high mortality rate can be reduced by early treatment following precancerous screening. Currently, the gold standard for screening bladder tumors is histological examination of biopsy specimen, which is both invasive and time-consuming. In this study ex vivo urine fluorescence cytology is investigated to offer a timely and biopsy-free means for detecting bladder cancers. Sediments in patients' urine samples were extracted and incubated with a novel photosensitizer, hypericin. Laser confocal microscopy was used to capture the fluorescence images at an excitation wavelength of 488 nm. Images were subsequently processed to single out the exfoliated bladder cells from the other cells based on the cellular size. Intensity histogram of each targeted cell was plotted and feature vectors, derived from the histogram moments, were used to represent each sample. A difference in the distribution of the feature vectors of normal and low-grade cancerous bladder cells was observed. Diagnostic algorithm for discriminating between normal and low-grade cancerous cells is elucidated in this paper. This study suggests that the fluorescence intensity profiles of hypericin in bladder cells can potentially provide an automated quantitative means of early bladder cancer diagnosis.

  18. 18F-FDG PET/CT in Bladder Cancer.

    Science.gov (United States)

    Tagliabue, Luca; Russo, Giovanna; Lucignani, Giovanni

    2016-12-01

    Urinary clearance of F-FDG and variability in bladder wall FDG uptake may hamper the interpretation and limit the use of FDG-PET/CT for imaging bladder tumors. Nevertheless, careful combined evaluation of both CT and FDG-PET images of the urinary tract can provide useful findings. We present 2 cases of bladder cancer detected by FDG-PET/CT. These cases suggest that FDG uptake can be indicative of malignancy in bladder cancer when viewed in conjunction with CT scans and that whole-body FDG-PET/CT scans should always be reviewed with particular attention to the urinary tract because abnormalities suggestive of bladder cancer can be found unexpectedly.

  19. Vinflunine in the treatment of bladder cancer

    Directory of Open Access Journals (Sweden)

    Mark Bachner

    2008-11-01

    Full Text Available Mark Bachner, Maria De Santis3rd Medical Department – Center for Oncology and Hematology, Kaiser Franz Josef-Spital der Stadt Wien, and Ludwig Boltzmann-Institute for Applied Cancer Research Vienna (LBI-ACR VIEnna, Cluster Translational Oncology, Kaiser Franz Josef-Spital der Stadt Wien, and Applied Cancer Research – Institution for Translational Research Vienna (ACR-ITR VIEnna/CEADDP, Vienna, AustriaAbstract: Vinflunine (VFL is a third-generation bifluorinated semi-synthetic vinca alkaloid obtained by superacidic chemistry from its parent compound, vinorelbine. As with the other vinca alkaloids, the main antineoplastic effects of VFL arise from its interaction with tubulin, the major component of microtubules in mitotic spindles. In contrast to other vinca alkaloids, VFL shows some distinctive properties in terms of tubulin binding, possibly explaining its superior antitumor activity in vitro and in vivo compared with vinorelbine as well as its excellent safety profile. In transitional cell carcinoma (TCC, two single-agent phase II trials were performed testing VFL in platinum-pretreated patients, showing moderate response rates and promising disease control rates. Therefore, the first phase III trial in modern times for second-line TCC of the urothelium was designed in order to further investigate the activity of VFL. First results were presented at the 2008 ASCO conference. VFL appears to be a possible treatment option for patients with TCC progressing after first-line platinum-containing chemotherapy.Keywords: vinflunine, transitional cell carcinoma (TCC of the bladder, bladder cancer, chemotherapy, second-line chemotherapy

  20. Hemipelvic irradiation for superficial bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tashiro, Kazuya; Machida, Toyohei; Ooishi, Yukihiko; Ueda, Masataka; Kido, Akira; Wada, Tetsuro; Yoshigoe, Fukuo; Yamashita, Takashi; Mochizuki, Sachio

    1985-02-01

    In 15 patients with superficial bladder cancer hemipelvic irradiation was performed for prevention of relapse of cancer and decrease in side effects with following results. All patients received TUR-Bt at our department during the six years period from 1978 to 1983. As to stages, one was classified as Ta, 11 as T 1 and 3 as T 2, and pathologic diagnosis was transitional epithelial carcinoma of grade 1 in 1 case, grade 2 in 8 cases and grade 3 in 6 cases. Irradiation was started from the 7 th to 14 th day after TUR-Bt. At first, hemipelvic anterior and posterior field including the field from the affected pelvis to 1 to 2 cm beyond the midline toward the contralateral side and from the aortic bifurcation to the prostatic urethra were irradiated at a dose of 45 Gy. Then, whole bladder field was given an additional rotation irradiation of 20 Gy. The mean observation period was 43 months (ranging from 12 to 79 months) and relapse of cancer was observed in 6 cases out of 15 cases (40%). The site of relapse was in the irradiated site in 2 cases, contralateral site in 3 cases and both side in 1 cases. However, in all of the relapsed cases no aggravation in differential degree or progression in stage was observed. As the side effects, radiation cystitis developed as a delayed damage in 1 case. Thus, although no efficacy for prevention of relapse which we had expected was not seen, this irradiation method effectively inhibited the progression of lesion and development of delayed damage. (author).

  1. Clinical states model for biomarkers in bladder cancer.

    Science.gov (United States)

    Apolo, Andrea B; Milowsky, Matthew; Bajorin, Dean F

    2009-09-01

    Bladder cancer is a significant healthcare problem in the USA, with a high recurrence rate, the need for expensive continuous surveillance and limited treatment options for patients with advanced disease. Research has contributed to an understanding of the molecular pathways involved in the development and progression of bladder cancer, and that understanding has led to the discovery of potentially diagnostic, predictive and prognostic biomarkers. In this review, a clinical states model of bladder cancer is introduced and integrated into a paradigm for biomarker development. Biomarkers are systematically incorporated with predefined end points to aid in clinical management.

  2. A murine model for bladder cancer.

    Science.gov (United States)

    Murphy, G P; Sandberg, A A; Pontes, J E; Ochi, H; Yoshida, M; Williams, P D

    1984-01-01

    Growth characteristics, survival time, and various other parameters such as chromosome studies and DNA synthesis were evaluated in a transplantable transitional cell mouse bladder tumor induced by N-[4-5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT). When the tumor was implanted subcutaneously, the mice were observed to survive mean 43 + 7 days (mean +/- SEM) with an average tumor burden of mean 8.45 +/- 0.60 gm (mean +/- SEM) of solid tumor tissue. In the tumor control animals, lung metastasis was noted in 3 animals at 42-49 days post implantation. The histological appearance of the primary tumor and the lung metastasis presented an undifferentiated anaplastic tumor with many spindle cells. The modal number of chromosome is 65 with several markers identifiable as abnormal in morphology. A significant decrease (p less than 0.001) in DNA synthesis was noted between 13 days and 20 days post implantation. In the evaluation of chemotherapy drugs, Cis-dichloro-trans-dihydroxy-bis-iso propylamine platinum IV (CHIP), Cis-diaminedichloroplatinum II (DDP), Cyclophosphamide (CTX) and Methotrexate (MTX) tumor growth was significantly retarded (p less than 0.005) in the DDP treated groups, however survival was not improved. Survival was significantly improved in the CTX treated group (p less than 0.001), although no significant decrease was noted in tumor growth. Lung metastasis was noted in all groups. This model has certain characteristics which make it a good model to study locally invasive bladder cancer.

  3. Trimodality therapy in bladder cancer: who, what, and when?

    Science.gov (United States)

    Premo, Christopher; Apolo, Andrea B; Agarwal, Piyush K; Citrin, Deborah E

    2015-05-01

    Radical cystectomy is a standard treatment of nonmetastatic, muscle-invasive bladder cancer. Treatment with trimodality therapy consisting of maximal transurethral resection of the bladder tumor followed by concurrent chemotherapy and radiation has emerged as a method to preserve the native bladder in highly motivated patients. Several factors can affect the likelihood of long-term bladder preservation after trimodality therapy and therefore should be taken into account when selecting patients. New radiation techniques such as intensity modulated radiation therapy and image-guided radiation therapy may decrease the toxicity of radiotherapy in this setting. Novel chemotherapy regimens may improve response rates and minimize toxicity.

  4. New malignancies following cancer of the urinary bladder: analysis of German cancer registry data.

    Science.gov (United States)

    Lehnert, M; Kraywinkel, K; Pesch, B; Holleczek, B; Brüning, T

    2012-05-01

    This analysis aimed at occurrence and distribution patterns of new malignancies following bladder cancer. Standardised incidence ratios (SIRs) were calculated for two German population-based cancer registries of North Rhine-Westphalia (NRW) and Saarland to access risks for subsequent primaries. An elevated risk for secondary cancer of any site but urothelium was observed in NRW men [SIR 1.35, 95% confidence interval (CI) 1.22-1.49]. The corresponding risk in Saarland was not significantly elevated (SIR 1.06, 95% CI 0.97-1.15). In data of both registries excess risks were observed for cancer of the respiratory tract (SIR 1.54, CI 1.23-1.89 in NRW men) and the prostate (SIR 1.91, 95% CI 1.61-2.24 in NRW; SIR 1.25, 95% CI 1.07-1.45 in Saarland). Common risk factors and incidental findings during follow-up care of bladder cancer patients might explain most of the observed patterns. In addition SIRs were throughout particular high for subsequent cancer of the renal pelvis and the ureter due to pathological characteristics of urothelial neoplasms.

  5. Is the inverse association between selenium and bladder cancer due to confounding by smoking?

    Science.gov (United States)

    Beane Freeman, Laura E; Karagas, Margaret R; Baris, Dalsu; Schwenn, Molly; Johnson, Alison T; Colt, Joanne S; Jackson, Brian; Hosain, G M Monawar; Cantor, Kenneth P; Silverman, Debra T

    2015-04-01

    Selenium has been linked to a reduced risk of bladder cancer in some studies. Smoking, a well-established risk factor for bladder cancer, has been associated with lower selenium levels in the body. We investigated the selenium-bladder cancer association in subjects from Maine, New Hampshire, and Vermont in the New England Bladder Cancer Case-Control Study. At interview (2001-2005), participants provided information on a variety of factors, including a comprehensive smoking history, and submitted toenail samples, from which we measured selenium levels. We estimated odds ratios and 95% confidence intervals among 1,058 cases and 1,271 controls using logistic regression. After controlling for smoking, we saw no evidence of an association between selenium levels and bladder cancer (for fourth quartile vs. first quartile, odds ratio (OR) = 0.98, 95% confidence interval (CI): 0.77, 1.25). When results were restricted to regular smokers, there appeared to be an inverse association (OR = 0.76, 95% CI: 0.58, 0.99); however, when pack-years of smoking were considered, this association was attenuated (OR = 0.91, 95% CI: 0.68, 1.20), indicating potential confounding by smoking. Despite some reports of an inverse association between selenium and bladder cancer overall, our results, combined with an in-depth evaluation of other studies, suggested that confounding from smoking intensity or duration could explain this association. Our study highlights the need to carefully evaluate the confounding association of smoking in the selenium-bladder cancer association.

  6. Bladder cancer in HIV-infected adults: an emerging concern?

    Directory of Open Access Journals (Sweden)

    Sylvain Chawki

    2014-11-01

    Full Text Available Introduction: As HIV-infected patients get older more non-AIDS-related malignancies are to be seen. Cancer now represents almost one third of all causes of deaths among HIV-infected patients (1. Albeit bladder cancer is one of the most common malignancy worldwide (2, only 13 cases of bladder cancer in HIV-infected patients have been reported in the literature so far (3. Materials and Methods: We conducted a monocentric study in our hospital. We selected all patients who were previously admitted (from 1998 to 2013 in our hospital with diagnoses of HIV and bladder cancer. The objective was to assess the prevalence and characteristics of bladder cancers in HIV-infected patients in our hospital. Results: Based on our administrative HIV database (6353 patients, we found 15 patients (0.2% with a bladder cancer. Patients’ characteristics are presented in Table 1. Patients were mostly men and heavy smokers. Their median nadir CD4 cell count was below 200 and most had a diagnosis of AIDS. A median time of 14 years was observed in those patients, between the diagnosis of HIV-infection and the occurrence of bladder cancer, although in patients much younger (median age 56 than those developing bladder cancer without HIV infection (71.1 years (4. Haematuria was the most frequent diagnosis circumstance in HIV-infected patients who had relatively preserved immune function on highly active antiretroviral therapy (HAART. Histopathology showed relatively advanced cancers at diagnosis with a high percentage of non transitional cell carcinoma (TCC tumor and of TCC with squamous differentiation, suggesting a potential role for human papilloma virus (HPV co-infection. Death rate was high in this population. Conclusions: Bladder cancers in HIV-infected patients remain rare but occur in relatively young HIV-infected patients with a low CD4 nadir, presenting with haematuria, most of them being smokers, and have aggressive pathological features that are associated with

  7. Does urothelial cancer of bladder behave differently in young patients?

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-hua; LI You-yuan; HU Zhi-quan; ZHU Hui; ZHUANG Qian-yuan; QI Yong; YE Zhang-qun

    2012-01-01

    Background Bladder urothelial cancer has been diagnosed at an increasing rate among young adults in China while the clinical outcomes remain highly controversial.To optimize the management of young patients with bladder cancer,we examined whether bladder urothelial cancer in young patients behaved differently from that in the elder patients.Methods From 1994 to 2008,a database of bladder urothelial cancer patients at a major tertiary medical center was retrospectively reviewed.The clinical and pathological parameters of patients who were less than 40 years of age and a series of patients older than 40 years of age as the control group during the same period were compared.A survival analysis was performed using the Kaplan-Meier method and log-rank test,and Cox regression was performed to identify clinical parameters that affected the clinic outcomes.Results Young bladder cancer patients had a lower male-to-female ratio and were less likely to have advanced stages and high-grade cancers at the initial diagnosis.Tumors in young bladder cancer patients tended to be less multifocal at diagnosis.In addition,young patients had a lower recurrence rate and longer recurrence interval than older patients.The Kaplan-Meier curve and Log-rank test showed that young patients had significantly better cancer specific survival than old patients.The univariats and multivariate Cox regression analysis revealed that tumor grade is the sole predictor for tumor recurrence in young patients.Conclusions Young patients with bladder cancer have favorable pathological features and clinical outcomes than older patients.These findings argue for more conservative management approaches for young patients with bladder cancer.

  8. Prospective study of body mass index, height, physical activity and incidence of bladder cancer in US men and women.

    Science.gov (United States)

    Holick, Crystal N; Giovannucci, Edward L; Stampfer, Meir J; Michaud, Dominique S

    2007-01-01

    We evaluated prospectively the association between body mass index (BMI), height, recreational physical activity and the risk of bladder cancer among US adults. Data were used from 2 ongoing cohorts, the Health Professionals Follow-up Study and the Nurses' Health Study, with 3,542,012 years of follow-up and 866 incident bladder cancer cases (men = 507; women = 359) for the anthropometric analysis and 1,890,476 years of follow-up and 706 incident bladder cancer cases (men = 502; women = 204) for the physical activity analysis. Cox proportional hazard models were used to estimate incidence rate ratios (RR) and 95% confidence intervals (CI) between BMI, height, physical activity and bladder cancer risk adjusting for age, pack-years of cigarette smoking and current smoking. Estimates from each cohort were pooled using a random-effects model. We observed no association between baseline BMI and bladder cancer risk, even when we compared a BMI of > or =30 kg/m(2) to a BMI of 18-22.9 kg/m(2) [pooled multivariate (MV) RR, 1.16; 95% CI: 0.89-1.52]. A weak, but statistically significant, association was observed for the same comparison after excluding bladder cancer cases diagnosed within the first 4 years of follow-up (pooled MV RR, 1.33; 95% CI: 1.01-1.76). Height was not related to bladder cancer risk (pooled MV RR, 0.82; 95% CI: 0.65-1.03, top vs. bottom quintile). Total recreational physical activity also was not associated with the risk of bladder cancer (pooled MV RR, 0.97; 95% CI: 0.77-1.24, top vs. bottom quintile). Our findings do not support a role for BMI, height or physical activity in bladder carcinogenesis.

  9. Efficient intravesical therapy of bladder cancer with cationic doxorubicin nanoassemblies

    Directory of Open Access Journals (Sweden)

    Jin X

    2016-09-01

    Full Text Available Xun Jin,1 Peilan Zhang,1 Li Luo,1 Hao Cheng,1 Yunzu Li,1 Ting Du,1 Bingwen Zou,2 Maling Gou1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People’s Republic of China; 2Department of Thoracic Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China Abstract: Nanoparticles have promising applications in drug delivery for cancer therapy. Herein, we prepared cationic 1,2-dioleoyl-3-trimethylammonium propane/methoxypoly (ethyleneglycol (DPP nanoparticles to deliver doxorubicin (Dox for intravesical therapy of bladder cancer. The DPP micelles have a mean dynamic diameter of 18.65 nm and a mean zeta potential of +19.6 mV. The DPP micelles could prolong the residence of Dox in the bladder, enhance the penetration of Dox into the bladder wall, and improve cellular uptake of Dox. The encapsulation by DPP micelles significantly improved the anticancer effect of Dox against orthotopic bladder cancer in vivo. This work described a Dox-loaded DPP nanoparticle with potential applications in intravesical therapy of bladder cancer. Keywords: bladder cancer, drug delivery, nanoparticles, intravesical therapy

  10. Genetic variant as a marker for bladder cancer therapy

    Science.gov (United States)

    Patients who have inherited a specific common genetic variant develop bladder cancer tumors that strongly express a protein known as prostate stem cell antigen (PSCA), which is also expressed in many pancreatic and prostate tumors, according to research a

  11. THE STUDY OF MICROSATELLITES ALTERATION IN DIAGNOSES OF BLADDER CANCER

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Bladder cancer is the fourth most commonmalignancy in men and the eighth most commoncancer in women.Conventional approaches fordiagnosis includes cystoscopy and urine cytology.50%of lowgrade or superficial carcinomas may bemissed in urine cytology.Cystoscopic examinationremains the gold standard for detecting bladdercancer or during follow-up.However,thisapproach is costly,invasive and uncomfortable[1].The early diagnosis is essential for better therapyselectionin patients with bladder cancers.Thus,themajor...

  12. 30. Knockdown of IGF-IR by Antisense Oligodeoxynucleotide auguments the sensitivity of bladder cancer cells to MMC

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AND AIM: Transitional cell carcinoma (TCC) of the bladder represents the fifth most prevalent malignancy in Western population, with peak incidence found in males of the 50-to 70- year-old age group. A major problem in the management of bladder cancer is the low sensitivity of a large proportion (approximately 40%) among bladder tumors to chemotherapy and the high risk for recurrence of bladder tumors after transurethral resection. So drug resistance, especially in its multiple type forms, remains a major and difficult problem to resolve in bladder cancer therapy. This phenomenon has often been ascribed to strictly pharmacolo-gic factors, such as the overexpression of multidrug transporters P-glycoprotein, multidrug resistance related protein (MRP), and other variables closely implicated DNA repair and induction/modulation of apoptosis, such as P53 and the Bcl-protein family. Furthermore, it has been recently shown that certain growth factors(IGFs etc) may be involved in the mechanism of drug resistance. Clearly, these findings suggest the design of new strategies that might improve bladder tumor response to chemotherapy. Results have previously shown that human bladder tumor cell lines may be adapted to grow in the complete absence of serum or any other growth supplement and that this can be explained on the basis of autocrine stimulation. The acquirement of autonomous growth capacity was likely to be an important element in the oncogenesis of bladder tumors. Furthermore, criss-cross experiments showed that supernatants stimulated not only proliferation of the autologous cell line of bladder cancer, but also growth of the other bladder cancer cell lines, suggesting the production of common autocrine factors in bladder tumor cells. Some factors or their receptors involved in autocrine loop mechanism of bladder tumor cells have been confirmed, such as IL-6, the epidermal growth factor receptor, IFN-beta, transferrins-like substance etc. But certain factors which may

  13. Consistent genomic alterations in carcinoma in situ of the urinary bladder confirm the presence of two major pathways in bladder cancer development

    DEFF Research Database (Denmark)

    Zieger, Karsten; Marcussen, Niels; Borre, Michael

    2009-01-01

    Bladder cancer develops through different pathways, provisionally entitled "papillary" and "invasive." Carcinoma in situ (CIS) is thought to be the precursor of invasive bladder cancer. However, little is known about chromosomal alterations of these clinically important lesions, and the relations......Bladder cancer develops through different pathways, provisionally entitled "papillary" and "invasive." Carcinoma in situ (CIS) is thought to be the precursor of invasive bladder cancer. However, little is known about chromosomal alterations of these clinically important lesions......, and the relationship between chromosomal alterations and the different pathways. We laser-microdissected 12 CIS and 4 dysplasia samples concomitant to invasive bladder cancer. We determined genome-wide chromosome copy number changes and loss of heterozygosity (LOH) using Mapping 10K SNP microarrays. We further......3 mutations mutually exclusive. No FGFR3 mutations were found in 23 CIS and dysplasia samples. Based on this, we classified high-risk non-muscle-invasive bladder tumors according to FGFR3 mutations and chromosomal changes into papillary and CIS-type tumors with high correlation to CIS status (p = 0...

  14. Preoperative balloon occluded arterial infusion chemotherapy for locally invasive bladder cancer. Accurate staging for bladder preservation

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, Norio; Arima, Kiminobu; Kawamura, Juichi [Mie Univ., Tsu (Japan). School of Medicine; Tochigi, Hiromi

    1999-02-01

    The possibility of bladder preservation by preoperative balloon occluded arterial infusion (BOAI) chemotherapy was studied in 111 patients with locally invasive bladder cancer. BOAI was performed by blocking the blood flow of the internal iliac artery and by performing intra-arterial infusion of adriamycin (50 mg/body) and cisplatin (100 mg/body). Before BOAI the clinical diagnosis was T2 in 36, T3a in 29, T3b in 27, T4 in 11 and after BOAI it was T0 in 1, T1 in 27, T2 in 25, T3a in 20, T3b in 20, and T4 in 10. Down staging was observed on diagnostic images in 46.6%. Thirty patients (27.0%) received transurethral resection of bladder tumor (TUR-Bt) and their bladder could be preserved. The 5-year cancer-specific survival rate was 100% in pT0 (n=9), 97.5% in pT1 (n=47), 79.9% in pT2 (n=21), 80.0% in pT3a (n=6), 39.9% in pT3b (n=18) and 51.9% in pT4 cases (n=9). For the bladder preservation, accurate staging diagnosis is required. Since 1992, endorectal magnetic resonance imaging (MRI) has been used in addition to imaging diagnosis for improving the accuracy of staging diagnosis. The accuracies of staging diagnosis with and without endorectal MRI were 62.5% and 44.0%, respectively. BOAI as a neoadjuvant chemotherapy has the possibility of bladder-preserving therapy in locally invasive bladder cancer. Also, the endorectal MRI can improve the accuracy of staging diagnosis, which is important for the bladder preservation. (author)

  15. UDP-glucuronosyltransferase 2B7 C802T (His268Tyr) polymorphism in bladder cancer cases.

    Science.gov (United States)

    Zimmermann, Anna; Blaszkewicz, Meinolf; Roth, Gerhard; Seidel, Thilo; Dietrich, Holger; Schutschkow, Olga; Bolt, Hermann M; Golka, Klaus

    2008-01-01

    A study of Chinese benzidine workers indicated elevated levels of UDP-glucuronosyltransferase (UGT) 2B7 T/T activity in carriers for development of bladder cancer. The present study was designed to investigate the possible impact of the presence of UGT2B7 genotype on bladder cancer risk in Caucasians. UGT2B7 polymorphism at locus C(802)T (His(268)Tyr) was detected using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based procedure. The study group consisted of 211 bladder cancer cases and 210 controls suffering from different urological diseases, but without any history of cancer. Both groups were recruited from a Department of Urology located in a center of former chemical and rubber industries in Germany. Furthermore, 171 bladder cancer cases with a history of occupational exposure to aromatic amines surveyed for compensation due to an occupational disease were investigated. T/T genotype frequencies in bladder cancer cases, urological controls, and exposed patients appeared similar (27 vs. 35 vs. 25%). This study indicated that there were ethnic differences between Caucasian and Chinese general populations with respect to the UGT2B7 genotype. Furthermore, in contrast to an earlier investigation in benzidine-exposed Chinese bladder cancer patients, no relevant differences between bladder cancer patients and urological hospital controls were observed in Germany.

  16. Isorhapontigenin (ISO) Inhibits Invasive Bladder Cancer Formation In Vivo and Human Bladder Cancer Invasion In Vitro by Targeting STAT1/FOXO1 Axis.

    Science.gov (United States)

    Jiang, Guosong; Wu, Amy D; Huang, Chao; Gu, Jiayan; Zhang, Liping; Huang, Haishan; Liao, Xin; Li, Jingxia; Zhang, Dongyun; Zeng, Xingruo; Jin, Honglei; Huang, Haojie; Huang, Chuanshu

    2016-07-01

    Although our most recent studies have identified Isorhapontigenin (ISO), a novel derivative of stilbene that isolated from a Chinese herb Gnetum cleistostachyum, for its inhibition of human bladder cancer growth, nothing is known whether ISO possesses an inhibitory effect on bladder cancer invasion. Thus, we addressed this important question in current study and discovered that ISO treatment could inhibit mouse-invasive bladder cancer development following bladder carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) exposure in vivo We also found that ISO suppressed human bladder cancer cell invasion accompanied by upregulation of the forkhead box class O 1 (FOXO1) mRNA transcription in vitro Accordingly, FOXO1 was profoundly downregulated in human bladder cancer tissues and was negatively correlated with bladder cancer invasion. Forced expression of FOXO1 specifically suppressed high-grade human bladder cancer cell invasion, whereas knockdown of FOXO1 promoted noninvasive bladder cancer cells becoming invasive bladder cancer cells. Moreover, knockout of FOXO1 significantly increased bladder cancer cell invasion and abolished the ISO inhibition of invasion in human bladder cancer cells. Further studies showed that the inhibition of Signal transducer and activator of transcription 1 (STAT1) phosphorylation at Tyr701 was crucial for ISO upregulation of FOXO1 transcription. Furthermore, this study revealed that metalloproteinase-2 (MMP-2) was a FOXO1 downstream effector, which was also supported by data obtained from mouse model of ISO inhibition BBN-induced mouse-invasive bladder cancer formation. These findings not only provide a novel insight into the understanding of mechanism of bladder cancer's propensity to invasion, but also identify a new role and mechanisms underlying the natural compound ISO that specifically suppresses such bladder cancer invasion through targeting the STAT1-FOXO1-MMP-2 axis. Cancer Prev Res; 9(7); 567-80. ©2016 AACR.

  17. Lymphatic vessel density and function in experimental bladder cancer

    Directory of Open Access Journals (Sweden)

    Maier Julie

    2007-11-01

    Full Text Available Abstract Background The lymphatics form a second circulatory system that drains the extracellular fluid and proteins from the tumor microenvironment, and provides an exclusive environment in which immune cells interact and respond to foreign antigen. Both cancer and inflammation are known to induce lymphangiogenesis. However, little is known about bladder lymphatic vessels and their involvement in cancer formation and progression. Methods A double transgenic mouse model was generated by crossing a bladder cancer-induced transgenic, in which SV40 large T antigen was under the control of uroplakin II promoter, with another transgenic mouse harboring a lacZ reporter gene under the control of an NF-κB-responsive promoter (κB-lacZ exhibiting constitutive activity of β-galactosidase in lymphatic endothelial cells. In this new mouse model (SV40-lacZ, we examined the lymphatic vessel density (LVD and function (LVF during bladder cancer progression. LVD was performed in bladder whole mounts and cross-sections by fluorescent immunohistochemistry (IHC using LYVE-1 antibody. LVF was assessed by real-time in vivo imaging techniques using a contrast agent (biotin-BSA-Gd-DTPA-Cy5.5; Gd-Cy5.5 suitable for both magnetic resonance imaging (MRI and near infrared fluorescence (NIRF. In addition, IHC of Cy5.5 was used for time-course analysis of co-localization of Gd-Cy5.5 with LYVE-1-positive lymphatics and CD31-positive blood vessels. Results SV40-lacZ mice develop bladder cancer and permitted visualization of lymphatics. A significant increase in LVD was found concomitantly with bladder cancer progression. Double labeling of the bladder cross-sections with LYVE-1 and Ki-67 antibodies indicated cancer-induced lymphangiogenesis. MRI detected mouse bladder cancer, as early as 4 months, and permitted to follow tumor sizes during cancer progression. Using Gd-Cy5.5 as a contrast agent for MRI-guided lymphangiography, we determined a possible reduction of lymphatic

  18. Current therapeutic strategies for invasive and metastatic bladder cancer

    Directory of Open Access Journals (Sweden)

    Vishnu P

    2011-07-01

    Full Text Available Prakash Vishnu, Jacob Mathew, Winston W TanDivision of Hematology Oncology, Mayo Clinic, Jacksonville, FL, USABackground: Bladder cancer is one of the most common cancers in Europe, the United States, and Northern African countries. Muscle-invasive bladder cancer is an aggressive epithelial tumor, with a high rate of early systemic dissemination. Superficial, noninvasive bladder cancer can most often be cured; a good proportion of invasive cases can also be cured by a combined modality approach of surgery, chemotherapy, and radiation. Recurrences are common and mostly manifest as metastatic disease. Those with distant metastatic disease can sometime achieve partial or complete remission with combination chemotherapy.Recent developments: Better understanding of the biology of the disease has led to the incorporation of molecular and genetic features along with factors such as tumor grade, lympho-vascular invasion, and aberrant histology, thereby allowing identification of ‘favorable’ and ‘unfavorable’ cancers which helps a more accurate informed and objective selection of patients who would benefit from neoadjuvant and adjuvant chemotherapy. Gene expression profiling has been used to find molecular signature patterns that can potentially be predictive of drug sensitivity and metastasis. Understanding the molecular pathways of invasive bladder cancer has led to clinical investigation of several targeted therapeutics such as anti-angiogenics, mTOR inhibitors, and anti-EGFR agents.Conclusion: With improvements in the understanding of the biology of bladder cancer, clinical trials studying novel and targeted agents alone or in combination with chemotherapy have increased the armamentarium for the treatment of bladder cancer. Although the novel biomarkers and gene expression profiles have been shown to provide important predictive and prognostic information and are anticipated to be incorporated in clinical decision-making, their exact utility

  19. Synchronous triple urogenital cancer (renal cancer, bladder cancer, prostatic cancer). A case report

    Energy Technology Data Exchange (ETDEWEB)

    Takada, Tsuyoshi; Honda, Masahito; Momohara, Chikahiro; Komori, Kazuhiko; Fujioka, Hideki [Osaka Police Hospital (Japan)

    2002-04-01

    A case of synchronous triple urogenital cancer, which was comprised of renal cell carcinoma of the left kidney, transitional cell carcinoma of the urinary bladder, and adenocarcinoma of the prostate, is reported. A 72-year-old Japanese male patient was referred to our outpatient clinic with the complaint of asymptomatic hematuria. At that time, his serum of level of PSA was elevated to 20 ng/ml. Cystourethroscopy showed a papillary bladder tumor and coagula through the left urinary orifice. Ultrasonography, computed tomography and magnetic resonance imaging showed a mass lesion measuring about 6 cm by 5 cm in the left kidney. Angiography showed a hypervascular lesion measuring about 6 cm by 5 cm at the same site. Double cancer, consisting of renal cell carcinoma and transitional cell carcinoma of the urinary bladder, was suspected and we performed left total nephroureterectomy, hilar lymphadenectomy, and transurethral rection of the bladder tumor, one month later. At the same time, we performed a biopsy of the prostate. Histological diagnosis was renal cell carcinoma, clear cell carcinoma and transitional cell carcinoma of urinary bladder. Histological diagnosis of the prostate biopsy was moderately differentiated adenocarcinoma. Since this case fulfilled the criteria of Warren and Gates, it was classified as synchronous triple urogenital cancer. A review of the literature revealed 17 authentic cases of triple urogenital cancer, of which 14 and 10 cases were reported as a combination of renal cancer, bladder cancer and prostatic cancer, in the world and in Japan, respectively. Furthermore, he had been exposed to the atomic bomb explosion in Hiroshima in 1945. This carcinogenic precursor may be related to the development of the triple cancer. (author)

  20. Thyroid Cancer Risk Factors

    Science.gov (United States)

    ... Prevented? Thyroid Cancer Causes, Risk Factors, and Prevention Thyroid Cancer Risk Factors A risk factor is anything that ... Cancer? Can Thyroid Cancer Be Prevented? More In Thyroid Cancer About Thyroid Cancer Causes, Risk Factors, and Prevention ...

  1. Developments in diagnosis and prognosis of superficial bladder cancer

    NARCIS (Netherlands)

    Moonen, P.M.J.

    2007-01-01

    Non-muscle invasive bladder encompasses the relatively innocent low risk tumours, but also the potentially lethal high risk tumours. Low risk tumours have a high chance of recurrence, but high risk tumours have both a high risk of recurrence and progression. Progression to muscle-invasive disease im

  2. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Albrechtsen, Reidar; Dyrskjøt, Lars; Rudkjaer, Lise;

    2006-01-01

    PURPOSE: We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. EXPERIMENTAL DESIGN: ADAM12...... staining on tissue arrays of bladder cancers. The presence and relative amount of ADAM12 in the urine of cancer patients were determined by Western blotting and densitometric measurements, respectively. RESULTS: ADAM12 mRNA expression was significantly up-regulated in bladder cancer, as determined...... by microarray analysis, and the level of ADAM12 mRNA correlated with disease stage. Reverse transcription-PCR, quantitative PCR, and in situ hybridization validated the gene expression results. Using immunohistochemistry, we found ADAM12 protein expression correlated with tumor stage and grade. Finally, ADAM12...

  3. Is There an Association Between Ambient Air Pollution and Bladder Cancer Incidence?

    DEFF Research Database (Denmark)

    Pedersen, Marie; Stafoggia, Massimo; Weinmayr, Gudrun

    2016-01-01

    of information about lifetime exposure. Conclusions: There was no evidence of an association between exposure to outdoor air pollution levels at place of residence and risk of BC. Patient summary: We assessed the link between outdoor air pollution at place of residence and bladder cancer using the largest study...

  4. Treatment Options Available for Bacillus Calmette-Guerin Failure in Non-muscle-invasive Bladder Cancer

    NARCIS (Netherlands)

    Yates, D.R.; Brausi, M.A.; Catto, J.W.; Dalbagni, G.; Roupret, M.; Shariat, S.F.; Sylvester, R.J.; Witjes, J.A.; Zlotta, A.R.; Palou-Redorta, J.

    2012-01-01

    CONTEXT: Intravesical bacillus Calmette-Guerin (BCG) is a standard conservative treatment for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Many patients will experience recurrence or progression following BCG and are termed BCG failures. OBJECTIVE: To summarise the current tre

  5. Key concerns about the current state of bladder cancer: a position paper from the Bladder Cancer Think Tank, the Bladder Cancer Advocacy Network, and the Society of Urologic Oncology.

    Science.gov (United States)

    Lotan, Yair; Kamat, Ashish M; Porter, Michael P; Robinson, Victoria L; Shore, Neal; Jewett, Michael; Schelhammer, Paul F; deVere White, Ralph; Quale, Diane; Lee, Cheryl T

    2009-09-15

    Bladder cancer is the fifth most common cancer in the United States and, on a per capita basis, is the most expensive cancer from diagnosis to death. Unfortunately, National Cancer Institute funding for bladder cancer is quite low when compared with other common malignancies. Limited funding has stifled research opportunities for new and established investigators, ultimately encouraging them to redirect research efforts to other organ sites. Waning interest of scientists has further fueled the cycle of modest funding for bladder cancer. One important consequence of this has been a lack of scientific advancement in the field. Patient advocates have decidedly advanced research efforts in many cancer sites. Breast, prostate, pancreatic, and ovarian cancer advocates have organized highly successful campaigns to lobby the federal government and the medical community to devote increased attention and funding to understudied malignancies and to conduct relevant studies to better understand the therapy, diagnosis, and prevention of these diseases. Bladder cancer survivors have lacked a coordinated advocacy voice until recently. A concerted effort to align bladder cancer advocates, clinicians, and urologic organizations is essential to define the greatest needs in bladder cancer and to develop related solutions. This position paper represents a collaborative discussion to define the most concerning trends and greatest needs in the field of bladder cancer as outlined by the Bladder Cancer Think Tank, the Bladder Cancer Advocacy Network, and the Society of Urologic Oncology.

  6. Detection of Smac expression in bladder cancer and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    Guiyi Liao; Fuqing Zeng; Xianghui Yue; Liang Wang; Fangmin Cheng

    2006-01-01

    Objective: To detect the expression of second mitochondria-derived activator of caspase (Smac) in bladder cancer and discuss its clinical significance. Methods: Smac was detected in 15 specimens of normal bladder epithelium and 72 specimens of bladder cancer by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry at the level of gene and protein,respectively. Results: The differences of both Smac protein and mRNA expressions between normal mucous membrane of bladder and grade Ⅰ bladder cancer had no statistical significance ( P > 0.05). The expressions of Smac protein and its mRNA in bladder cancer decreased gradually with the advance of bladder cancer ( P < 0.01 and P < 0.05, respectively ). In invasive bladder cancer, the expressions of Smac protein and its mRNA were higher than those in superficial bladder cancer (P<0.01). Conclusions: Normal bladder epithelium has high expression of Smac while bladder cancer has low expression of Smac. The expression of Smac is closely related to the grade and stage of bladder cancer. Detection of Smac expression helps to judge the grade and stage of bladder cancer and Smac gene might become a valid target for gene therapy of bladder cancer.

  7. Tobacco smoke and bladder cancer--in the European Prospective Investigation into Cancer and Nutrition.

    NARCIS (Netherlands)

    Bjerregaard, B.K.; Raaschou-Nielsen, O.; Sorensen, M.; Frederiksen, K.; Christensen, J.; Tjonneland, A.; Overvad, K.; Chapelon, F.C.; Nagel, G.; Chang-Claude, J.; Bergmann, M.M.; Boeing, H.; Trichopoulos, D.; Trichopoulou, A.; Oikonomou, E.; Berrino, F.; Palli, D.; Tumino, R.; Vineis, P.; Panico, S.; Peeters, P.H.; Bueno-De-Mesquita, H.B.; Kiemeney, L.A.L.M.; Gram, I.T.; Braaten, T.; Lund, E.; Gonzalez, C.A.; Berglund, G.; Allen, N.; Roddam, A.W.; Bingham, S.; Riboli, E.

    2006-01-01

    The purpose of the present study was to investigate the association between smoking and the development of bladder cancer. The study population consisted of 429,906 persons participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), 633 of whom developed bladder cancer

  8. HPLC assisted Raman spectroscopic studies on bladder cancer

    Science.gov (United States)

    Zha, W. L.; Cheng, Y.; Yu, W.; Zhang, X. B.; Shen, A. G.; Hu, J. M.

    2015-04-01

    We applied confocal Raman spectroscopy to investigate 12 normal bladder tissues and 30 tumor tissues, and then depicted the spectral differences between the normal and the tumor tissues and the potential canceration mechanism with the aid of the high-performance liquid chromatographic (HPLC) technique. Normal tissues were demonstrated to contain higher tryptophan, cholesterol and lipid content, while bladder tumor tissues were rich in nucleic acids, collagen and carotenoids. In particular, β-carotene, one of the major types of carotenoids, was found through HPLC analysis of the extract of bladder tissues. The statistical software SPSS was applied to classify the spectra of the two types of tissues according to their differences. The sensitivity and specificity of 96.7 and 66.7% were obtained, respectively. In addition, different layers of the bladder wall including mucosa (lumps), muscle and adipose bladder tissue were analyzed by Raman mapping technique in response to previous Raman studies of bladder tissues. All of these will play an important role as a directive tool for the future diagnosis of bladder cancer in vivo.

  9. Bladder Cancer Detection Using Electrical Impedance Technique (Tabriz Mark 1

    Directory of Open Access Journals (Sweden)

    Ahmad Keshtkar

    2012-01-01

    Full Text Available Bladder cancer is the fourth most common malignant neoplasm in men and the eighth in women. Bladder pathology is usually investigated visually by cystoscopy. In this technique, biopsies are obtained from the suspected area and then, after needed procedure, the diagnostic information can be taken. This is a relatively difficult procedure and is associated with discomfort for the patient and morbidity. Therefore, the electrical impedance spectroscopy (EIS, a minimally invasive screening technique, can be used to separate malignant areas from nonmalignant areas in the urinary bladder. The feasibility of adapting this technique to screen for bladder cancer and abnormalities during cystoscopy has been explored and compared with histopathological evaluation of urinary bladder lesions. Ex vivo studies were carried out in this study by using a total of 30 measured points from malignant and 100 measured points from non-malignant areas of patients bladders in terms of their biopsy reports matching to the electrical impedance measurements. In all measurements, the impedivity of malignant area of bladder tissue was significantly higher than the impedivity of non-malignant area this tissue (<0.005.

  10. Bladder cancer detection using electrical impedance technique (tabriz mark 1).

    Science.gov (United States)

    Keshtkar, Ahmad; Salehnia, Zeinab; Keshtkar, Asghar; Shokouhi, Behrooz

    2012-01-01

    Bladder cancer is the fourth most common malignant neoplasm in men and the eighth in women. Bladder pathology is usually investigated visually by cystoscopy. In this technique, biopsies are obtained from the suspected area and then, after needed procedure, the diagnostic information can be taken. This is a relatively difficult procedure and is associated with discomfort for the patient and morbidity. Therefore, the electrical impedance spectroscopy (EIS), a minimally invasive screening technique, can be used to separate malignant areas from nonmalignant areas in the urinary bladder. The feasibility of adapting this technique to screen for bladder cancer and abnormalities during cystoscopy has been explored and compared with histopathological evaluation of urinary bladder lesions. Ex vivo studies were carried out in this study by using a total of 30 measured points from malignant and 100 measured points from non-malignant areas of patients bladders in terms of their biopsy reports matching to the electrical impedance measurements. In all measurements, the impedivity of malignant area of bladder tissue was significantly higher than the impedivity of non-malignant area this tissue (P < 0.005).

  11. Stage of urinary bladder cancer at first presentation

    Directory of Open Access Journals (Sweden)

    Al-Bazzaz Pishtewan

    2009-01-01

    Full Text Available The stage of urinary bladder cancer is an important factor in determining prognosis of the disease. This prospective study was performed to determine the stage of bladder cancer at first presentation at the Rizgary Hospital in the Erbil governorate in Iraqi Kurdistan. We evaluated 72 patients with bladder cancer. The grades and stages of bladder cancer of these patients were determined through physical examination and investigations. We found that 47.2% of patients had superficial cancer, 19.4% had tumor with invasion into the lamina propria and 30.6% of patients had tumor with invasion to muscle wall. Regional or distant metastases were found in 2.8% of patients. Well differentiated tumor was seen in 44.4% of the patients, moderately differentiated tumor was found in 38.9% and poorly differentiated tumor was found in 16.7% of the patients. Our study suggests that bladder cancer is diagnosed at a relatively early stage in the Erbil governorate. However, the situation can be further improved by adopting proper screening programs and performing appropriate investigations.

  12. Novel Simulation Model of Non-Muscle Invasive Bladder Cancer

    DEFF Research Database (Denmark)

    Patel, Sanjay R; Dinh, Tuan; Noah-Vanhoucke, Joyce

    2015-01-01

    Introduction: There have been no randomized controlled trials (RCTs) evaluating the clinical or economic benefit of mitomycin C intravesical therapy vs. radical cystectomy in patients with high-risk non-muscle invasive bladder cancer (NMIBC). We used the Archimedes computational model to simulate...... RCT comparing radical cystectomy versus intravesical mitomycin C (MMC) therapy to evaluate the clinical and economic outcomes for BCG-refractory NMIBC as well demonstrate the utility of computer based models to simulate a clinical trial. Methods: The Archimedes model was developed to generate...... and is more cost-effective when compared to those undergoing MMC. Simulation of clinical trials using computational models similar to the Archimedes model can overcome shortcomings of real-world clinical trials and may prove useful in the face of current medical cost-conscious era....

  13. PET/Computed Tomography in Renal, Bladder, and Testicular Cancer.

    Science.gov (United States)

    Bouchelouche, Kirsten; Choyke, Peter L

    2015-07-01

    Imaging plays an important role in the clinical management of cancer patients. Hybrid imaging with PET/computed tomography (CT) is having a broad impact in oncology, and in recent years PET/CT is beginning to have an impact in urooncology. In both bladder and renal cancers, there is a need to study the efficacy of other tracers than F-18 fluorodeoxyglucose (FDG), particularly tracers with limited renal excretion. Thus, new tracers are being introduced. This review focuses on the clinical role of FDG and other PET agents in renal, bladder, and testicular cancers.

  14. Quantitative Analysis of Differential Proteome Expression in Bladder Cancer vs. Normal Bladder Cells Using SILAC Method.

    Directory of Open Access Journals (Sweden)

    Ganglong Yang

    Full Text Available The best way to increase patient survival rate is to identify patients who are likely to progress to muscle-invasive or metastatic disease upfront and treat them more aggressively. The human cell lines HCV29 (normal bladder epithelia, KK47 (low grade nonmuscle invasive bladder cancer, NMIBC, and YTS1 (metastatic bladder cancer have been widely used in studies of molecular mechanisms and cell signaling during bladder cancer (BC progression. However, little attention has been paid to global quantitative proteome analysis of these three cell lines. We labeled HCV29, KK47, and YTS1 cells by the SILAC method using three stable isotopes each of arginine and lysine. Labeled proteins were analyzed by 2D ultrahigh-resolution liquid chromatography LTQ Orbitrap mass spectrometry. Among 3721 unique identified and annotated proteins in KK47 and YTS1 cells, 36 were significantly upregulated and 74 were significantly downregulated with >95% confidence. Differential expression of these proteins was confirmed by western blotting, quantitative RT-PCR, and cell staining with specific antibodies. Gene ontology (GO term and pathway analysis indicated that the differentially regulated proteins were involved in DNA replication and molecular transport, cell growth and proliferation, cellular movement, immune cell trafficking, and cell death and survival. These proteins and the advanced proteome techniques described here will be useful for further elucidation of molecular mechanisms in BC and other types of cancer.

  15. Results of radiotherapy on ureteric obstruction in muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Honnens De Lichtenberg, Mette; Miskowiak, J; Rolff, H

    1995-01-01

    To evaluate the effect of radiotherapy on ureteric obstruction due to muscle-invasive bladder cancer.......To evaluate the effect of radiotherapy on ureteric obstruction due to muscle-invasive bladder cancer....

  16. New and promising strategies in the management of bladder cancer.

    Science.gov (United States)

    Apolo, Andrea B; Vogelzang, Nicholas J; Theodorescu, Dan

    2015-01-01

    Bladder cancer is a complex and aggressive disease for which treatment strategies have had limited success. Improvements in detection, treatment, and outcomes in bladder cancer will require the integration of multiple new approaches, including genomic profiling, immunotherapeutics, and large randomized clinical trials. New and promising strategies are being tested in all disease states, including nonmuscle-invasive bladder cancer (NMIBC), muscle-invasive bladder cancer (MIBC), and metastatic urothelial carcinoma (UC). Efforts are underway to develop better noninvasive urine biomarkers for use in primary or secondary detection of NMIBC, exploiting our genomic knowledge of mutations in genes such as RAS, FGFR3, PIK3CA, and TP53 and methylation pathways alone or in combination. Recent data from a large, randomized phase III trial of adjuvant cisplatin-based chemotherapy add to our knowledge of the value of perioperative chemotherapy in patients with MIBC. Finally, bladder cancer is one of a growing list of tumor types that respond to immune checkpoint inhibition, opening the potential for new therapeutic strategies for treatment of this complex and aggressive disease.

  17. [Management of occupational bladder cancer in Japan (Vol. 1)].

    Science.gov (United States)

    Ishizu, Sumiko; Hashida, Chise

    2007-01-01

    By examining historical documents regarding occupational bladder cancer in Japan, we interpreted and followed the progress made in developing preventive measures against the outbreak of occupational bladder cancer in Japanese dye industries after World War II, and documented how these measures became well organized. During Dr. M. H. C. Williams's, who was an industrial physician for the British ICI Company, occasional visits to Japan, he encouraged the enforcement of such measures, considering them to be as important in occupational health in Japan as in Western countries. He received permission to implement these measures in Japanese dye companies. A urine cell diagnostic system was already being employed in Japanese industries as a method of diagnosing occupational bladder cancer, and its use was promoted by engineers, urologists, and pathologists even before the Industrial Safety and Health Law was enacted in 1972. It took about 10 years for these measures to become standardized industry-wide. The use of these measures has had a considerable effect on the early diagnosis of patients and extended patients' life spans. Eventually, the life spans of such patients became approximately the same as that of the average Japanese male. Some patients unfortunately died of occupational bladder cancer. Others were examined using these measures not only while employed but also after retirement. Therefore, some patients in whom occupational bladder cancer was detected are still alive at over eighty years of age.

  18. Pioglitazone and bladder cancer in human studies: is it diabetes itself, diabetes drugs, flawed analyses or different ethnicities?

    Science.gov (United States)

    Tseng, Chin-Hsiao

    2012-03-01

    This article reviews human observations on pioglitazone and bladder cancer risk. The PROspective pioglitAzone Clinical Trial In macroVascular Events trial showed an imbalance in bladder cancer between users of pioglitazone and placebo (14 versus six cases, p = 0.069). However, after excluding bladder cancer probably ascribed to other etiology, a blind assessment concluded that the imbalance might not be related to pioglitazone. Epidemiologic studies conducted in the United States and France using insurance databases independently suggested that pioglitazone use for >2 years might confer a 20%-40% higher risk. Another study evaluating bladder cancer risk in diabetic patients using the National Health Insurance in Taiwan did not find any incident bladder cancer case among 422 pioglitazone users for a follow-up of up to 3 years. Because observational studies may suffer from selection and information bias, and inadequate adjustment for confounders may inflate the estimated risk, causal inference from these studies should be interpreted with caution. While investigating cancer risk associated with a medication, indication bias should also be attended, especially when the medication is used at a late stage of the disease. Because pioglitazone is usually a second or third line antidiabetic agent, the users are always characterized by older age, longer diabetes duration, poorer glycemic control, and higher rates of complications and comorbidities. Biased estimates will also result if these differences are not appropriately addressed in the analyses. Current evidence neither concludes nor excludes a causal role of pioglitazone on bladder cancer. Clinical trials aiming at evaluating the risk of cancer associated with a medication is not ethical and may not be expected to provide an answer on the issue of pioglitazone-related bladder cancer. However, a meta-analysis using all available clinical trials to compare the bladder cancer risk between pioglitazone and comparators

  19. Pioglitazone (Actos) and bladder cancer: Legal system triumphs over the evidence.

    Science.gov (United States)

    Davidson, Mayer B

    2016-08-01

    In preclinical studies, pioglitazone was associated with bladder cancer in male rats (but not in female rats, mice dogs or monkeys). Because of this association, the Federal Drug Administration requested a large 10year epidemiological study to evaluate whether there was an association between bladder cancer and exposure to pioglitazone in patients. A 5-year interim report published in 2011 showed no significant association between ever vs never exposure to the drug but a significant association in patients exposed to pioglitazone for >2years. Importantly, the final 10year report did not confirm the 5year interim report finding no association between bladder cancer and pioglitazone, even after >4years of exposure to the drug. However, as would be expected, following the 5-year interim report, many epidemiological studies were carried out and civil litigation lawsuits began to be filed. Of the 23 epidemiological studies that have been published to date, 18 showed no association between bladder cancer and pioglitazone (5 with a combination of rosiglitazone and pioglitazone). Of the five that did show a significant association with pioglitazone, three could not be confirmed in the same population and in one of them there were significantly more risk factors for bladder cancer in the patients exposed to pioglitazone. In the fourth one, a significant association became non-significant when patients >79years were included. In the fifth one, detection bias was a major flaw. Currently, >11,000 legal cases have been filed, many of which claim emotional distress due to the fear of bladder cancer. To limit their legal costs, the pharmaceutical company has established a 2.4 billion dollar settlement pool. So much for evidence-based medicine.

  20. Ultraviolet B Irradiance and Incidence Rates of Bladder Cancer in 174 Countries

    Science.gov (United States)

    2010-03-01

    aromatic amines, rubber, or cable manufacturing have an increased risk of bladder cancer, mainly from exposure to chemical carcinogens commonly...such as differences among countries regarding both the presence of certain indus- tries and tobacco use. The possibility of confounding was...Eriksen M. The tobacco atlas. Geneva: WHO, 2002. 30. Armenian HK. Incubation periods of cancer: old and new. 31. 32. J Chronic Dis 1987;(40S 2

  1. Urine Telomerase for Diagnosis and Surveillance of Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Angela Lamarca

    2012-01-01

    Full Text Available Bladder cancer has increased incidence during last decades. For those patients with nonmuscle involved tumors, noninvasive diagnosis test and surveillance methods must be designed to avoid current cystoscopies that nowadays are done regularly in a lot of patients. Novel urine biomarkers have been developed during last years. Telomerase is important in cancer biology, improving the division capacity of cancer cells. Even urinary telomerase could be a potentially useful urinary tumor marker; its use for diagnosis of asymptomatic and symptomatic patients or its impact during surveillance is still unknown. Moreover, there will need to be uniformity and standardization in the assays before it can become useful in clinical practice. It does not seem to exist a real difference between the most classical assays for the detection of urine telomerase (TRAP and hTERT. However, the new detection methods with modified TeloTAGGG telomerase or with gold nanoparticles must also be taken into consideration for the correct development of this diagnosis method. Maybe the target population would be the high-risk groups within screening programs. To date there is no enough evidence to use it alone and to eliminate cystoscopies from the diagnosis and surveillance of these patients. The combination with cytology or FISH is still preferred.

  2. Pharmacogenomics: Biomarker-Directed Therapy for Bladder Cancer.

    Science.gov (United States)

    Jones, Robert T; Felsenstein, Kenneth M; Theodorescu, Dan

    2016-02-01

    The clinical management of bladder cancer has seen little change over the last three decades and there is pressing need to identify more effective treatments for advanced disease. Low clinical use of neoadjuvant therapies stems from historical limitations in the ability to predict patients most likely to respond to combination chemotherapies. This article focuses on recent molecular and genetic studies, highlighting promising clinical trials and retrospective studies, and discusses emerging trials that use predictive biomarkers to match patients with therapies to which they are most likely to respond. The implementation of predictive genomic and molecular biomarkers will revolutionize urologic oncology and the clinical management of bladder cancer.

  3. Cathepsin-D And Tnf-α in Bladder Cancer

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    T. Salman

    1996-01-01

    Full Text Available In a study of 34 normal healthy controls, 35 patients with urinary tract bilharziasis and 93 bladder cancer patients (62 of them are operable cases and 31 are non-operable ones, serum tumor necrosis factor alpha (TNF-α and cytosolic Cathepsin-D were estimated. Though both potential markers were elevated in bladder cancer patients, neither Cathepsin-D nor TNF-α showed associations of prognostic value since there were no positive correlations with tumor stages, grades or association of tumors with bilharzia ova or lymph node involvement.

  4. Analysis of variants in DNA damage signalling genes in bladder cancer

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    Bishop D Timothy

    2008-07-01

    Full Text Available Abstract Background Chemicals from occupational exposure and components of cigarette smoke can cause DNA damage in bladder urothelium. Failure to repair DNA damage by DNA repair proteins may result in mutations leading to genetic instability and the development of bladder cancer. Immunohistochemistry studies have shown DNA damage signal activation in precancerous bladder lesions which is lost on progression, suggesting that the damage signalling mechanism acts as a brake to further tumorigenesis. Single nucleotide polymorphisms (SNPs in DSB signalling genes may alter protein function. We hypothesized that SNPs in DSB signalling genes may modulate predisposition to bladder cancer and influence the effects of environmental exposures. Methods We recruited 771 cases and 800 controls (573 hospital-based and 227 population-based from a previous case-control study and interviewed them regarding their smoking habits and occupational history. DNA was extracted from a peripheral blood sample and genotyping of 24 SNPs in MRE11, NBS1, RAD50, H2AX and ATM was undertaken using an allelic discrimination method (Taqman. Results Smoking and occupational dye exposure were strongly associated with bladder cancer risk. Using logistic regression adjusting for age, sex, smoking and occupational dye exposure, there was a marginal increase in risk of bladder cancer for an MRE11 3'UTR SNP (rs2155209, adjusted odds ratio 1.54 95% CI (1.13–2.08, p = 0.01 for individuals homozygous for the rare allele compared to those carrying the common homozygous or heterozygous genotype. However, in the hospital-based controls, the genotype distribution for this SNP deviated from Hardy-Weinberg equilibrium. None of the other SNPs showed an association with bladder cancer and we did not find any significant interaction between any of these polymorphisms and exposure to smoking or dye exposure. Conclusion Apart from a possible effect for one MRE11 3'UTR SNP, our study does not support

  5. Is gall bladder cancer a bad cancer per se ?

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Gall bladder cancer (GBC) has one of the poorestoutcomes of all cancers. Early GBC is difficult todiagnose on even computed tomography. GB has nosubmucosa and the cancer infiltrates directly into themuscularis propria. GB wall is thin and important adjacentorgans viz. liver, duodenum and pancreas get easilyinfiltrated. Tumor in the GB neck often needs extendedright hepatectomy. Infiltration of duodenum/pancreasmay necessitate pancreato-duodenectomy or evenhepato-pancreato-duodenectomy. Mortality of surgicalprocedures, when performed for GBC, is higher thanwhen performed for other cancers. Survival in GBC,even after R0 resection, is poor. There is no proven roleof neo-adjuvant or adjuvant therapy for loco-regionallyadvanced GBC. There is no role of palliative surgeryin metastatic GBC. Early GBC is diagnosed incidentallyafter cholecystectomy for stones and requires reoperationfor completion extended cholecystectomy butunfortunately, most surgeons are not aware of this. GBChas a peculiar epidemiology and is uncommon in theWest and has, therefore, not received much attention.Preventive cholecystectomy for asymptomatic stonesis not recommended and there is no serum marker forscreening. With all factors pitched against it, it doesappear that GBC is a bad cancer per se !

  6. Incidental prostate cancer diagnosed at radical cystoprostatectomy for bladder cancer: disease-specific outcomes and survival

    Directory of Open Access Journals (Sweden)

    Joshua B. Kaelberer

    2016-09-01

    Conclusion: For men undergoing RCP for bladder cancer, the present study suggests that incidentally discovered prostate cancers, irrespective of pathologic stage, Gleason score, or clinical significance, do not impact 5-year disease control or survival outcomes.

  7. Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer

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    Kari T. Syvänen

    2014-05-01

    Full Text Available Neoadjuvant chemotherapy (NAC in muscle-invasive bladder cancer was introduced several years ago. Despite the evidence supporting its use in clinical practice, only a minority of patients who undergo radical cystectomy receive preoperative chemotherapy. In addition, recommendations and methods to detect patients who would benefit the most from NAC are still unclear. The European Association of Urology (EAU guidelines panel on muscle-invasive and metastatic bladder cancer recommends the use of cisplatin-based NAC for T2-T4a, cN0 M0 bladder cancer if the patient has a performance status ≥2 and if the renal function is not impaired, but the American Urological Association, for example, does not have any guideline recommendations on this topic at all. In this review we describe the current literature supporting NAC in association with radical cystectomy in muscle-invasive urothelial carcinoma of the bladder. Evidence acquisition was made searching the Medline database for original articles published before 1st February 2014, with search terms: “neoadjuvant chemotherapy”, “radical cystectomy”, and “invasive bladder cancer”.

  8. Susceptibility to urinary bladder cancer: relevance of rs9642880[T], GSTM1 0/0 and occupational exposure.

    Science.gov (United States)

    Golka, Klaus; Hermes, Matthias; Selinski, Silvia; Blaszkewicz, Meinolf; Bolt, Hermann M; Roth, Gerhard; Dietrich, Holger; Prager, Hans-Martin; Ickstadt, Katja; Hengstler, Jan G

    2009-11-01

    Recently, a genome-wide single nucleotide polymorphism association study has identified a sequence variant 30 kb upstream of the c-Myc gene (allele T of rs9642880) that confers susceptibility to bladder cancer. However, the role of exposure to bladder carcinogens has not been considered. This prompted us to analyse the relevance of this polymorphism in 515 bladder cancer cases and 893 controls where the quality and quantity of occupational exposure to bladder carcinogens has been documented. When we analysed a hospital-based case-control series not selected for occupational exposure, rs9642880[T] was influential, in contrast to GSTM1 0/0. However, in a case-control series of patients that have been occupationally exposed to aromatic amines and polycyclic aromatic hydrocarbons, rs9642880[T] was not influential but GSTM1 0/0 was significantly associated with bladder cancer risk. Therefore, the degree to which rs9642880[T] and GSTM1 0/0 confer susceptibility to urinary bladder cancer seems to depend on the extent of exposure to urinary bladder carcinogens.

  9. Bladder Diseases

    Science.gov (United States)

    ... frequent, urgent urination Bladder cancer Doctors diagnose bladder diseases using different tests. These include urine tests, x- ... National Institute of Diabetes and Digestive and Kidney Diseases

  10. Anterior urethral recurrence of superficial bladder cancer: its clinical significance.

    Directory of Open Access Journals (Sweden)

    Saika T

    2003-12-01

    Full Text Available The aim of this study was to reveal the clinical features of anterior urethral recurrence in patients with superficial bladder cancer, and to determine the appropriate treatment. Three hundred and three patients with superficial bladder cancer, who were newly diagnosed and initially treated conservatively in our hospital between 1965 and 1990, were followed for at least 5 years and their clinical outcomes were analyzed. Clinical factors, including anterior urethral recurrence, were evaluated statistically regarding tumor progression. Eight patients (2.6% had anterior urethral recurrence following superficial bladder cancer. Twenty-four patients (7.9% had tumor progression and 149 (49.2% had tumor recurrence. In a multivariate analysis using a logistic model, anterior urethral recurrence was the most important factor, followed by histological grade. Four of 5 patients who were treated for anterior urethral recurrent tumors by transurethral resection showed progression and died of the cancer within one year. Two of the remaining three patients who underwent radical cysto-urethrectomy at the time of anterior urethral recurrence survived. Anterior urethral recurrence following superficial bladder cancer is a predictor for rapid subsequent malignant progression. Once there is anterior urethral recurrence, radical intensive therapy, including radical cysto-urethrectomy, should be carried out immediately.

  11. Bladder cancer and occupational exposures in North Rhine-Westphalia, Germany.

    Science.gov (United States)

    Geller, Frank; Urfer, Wolfgang; Golka, Klaus

    2008-01-01

    The relationship between exposure to carcinogenic substances and development of bladder cancer was assessed from a case-control study conducted in North Rhine-Westphalia, Germany. The study consisted of 156 cases with bladder cancer and 336 controls with prostate cancer. The primary focus was the role of polycyclic aromatic hydrocarbons (PAHs), since most individuals were considered exposed mainly to substances in this group. Data were collected from male patients who had applied for cancer rehabilitation treatment. Nominally significant smoking-adjusted odds ratio (OR) estimates were obtained for frequent exposures to bitumen (OR = 2.92, 95% CI 1.32-6.48) and tar (OR = 2.09, 95% CI 1.04-4.21) and an ever exposure to paints (OR = 1.69, 95% CI 1.10-2.61). A frequent exposure to pitch showed a non-significant elevated risk (OR = 3.06, 95% CI 0.77-12.10).

  12. Circulating tumor cells in early bladder cancer: insight into micrometastatic disease.

    Science.gov (United States)

    Raimondi, Cristina; Gradilone, Angela; Gazzaniga, Paola

    2014-05-01

    Although several studies have demonstrated the prognostic and predictive potential of circulating tumor cells (CTCs), to date their evaluation still has not impacted the treatment strategy. There is wide consensus that CTC assessment would be more beneficial in early stage cancer, especially in those tumor types characterized by early progression and a lack of prognostic markers. Non-muscle-invasive bladder cancer represents an optimal model to this purpose. In fact, the rate of metastatic spread ranges between 20 and 40%, which is unacceptable for a 'superficial' tumor and unexpected in an early stage cancer. This may be due to the presence of non-clinically detectable micrometastases. CTCs may be used as a noninvasive, real-time tool for the stratification of early stage bladder cancer patients according to individual risk of progression.

  13. Collaborating to Move Research Forward: Proceedings of the 10th Annual Bladder Cancer Think Tank.

    Science.gov (United States)

    Kamat, Ashish M; Agarwal, Piyush; Bivalacqua, Trinity; Chisolm, Stephanie; Daneshmand, Sia; Doroshow, James H; Efstathiou, Jason A; Galsky, Matthew; Iyer, Gopa; Kassouf, Wassim; Shah, Jay; Taylor, John; Williams, Stephen B; Quale, Diane Zipursky; Rosenberg, Jonathan E

    2016-04-27

    The 10th Annual Bladder Cancer Think Tank was hosted by the Bladder Cancer Advocacy Network and brought together a multidisciplinary group of clinicians, researchers, representatives and Industry to advance bladder cancer research efforts. Think Tank expert panels, group discussions, and networking opportunities helped generate ideas and strengthen collaborations between researchers and physicians across disciplines and between institutions. Interactive panel discussions addressed a variety of timely issues: 1) data sharing, privacy and social media; 2) improving patient navigation through therapy; 3) promising developments in immunotherapy; 4) and moving bladder cancer research from bench to bedside. Lastly, early career researchers presented their bladder cancer studies and had opportunities to network with leading experts.

  14. What Are the Risk Factors for Bone Cancer?

    Science.gov (United States)

    ... skin cancer. Smoking is a risk factor for cancers of the lung, mouth, larynx, bladder, kidney, and several other organs. But having a risk factor, or even several, does not mean that you will get the disease. Most people with bone cancers do not have any apparent risk factors. Genetic ...

  15. The association of pioglitazone and urinary tract disease in type 2 diabetic Taiwanese: bladder cancer and chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Mei-Yueh Lee

    Full Text Available OBJECTIVE: Although studies have shown an association between pioglitazone and bladder cancer, the associated factors have not been identified. The aim of this study was to investigate the factors that may link pioglitazone to bladder cancer. MATERIALS AND METHODS: In total, 34,970 study subjects were identified from the National Health Insurance Research Database in 2003 with follow-up from 2005 to 2009. The demographic characteristics of patients who had used and had never used pioglitazone, including age, sex, diabetes duration, urinary tract disease, nephropathy, bladder cancer, and cumulative dose and duration of pioglitazone therapy, were analyzed using the χ2 test. Cox proportional hazard regression models were used to determine the independent effects of pioglitazone on bladder cancer and newly developed chronic kidney disease. RESULTS: Among 3,497 ever users and 31,473 never users of pioglitazone, the respective incident cases of bladder cancer were 12 (0.4% and 72 (0.2%, and for newly developed chronic kidney disease 245 (8.1% and 663 (2.3%, respectively. Ever use of pioglitazone [1.59(1.32-1.91], cumulative dose of pioglitazone 10,500 mg [1.34 (1.04-1.73], and duration of therapy 12 months [1.39 (1.09-1.76] were associated with the development of chronic kidney disease. CONCLUSIONS: There was no association of pioglitazone use with bladder cancer development, however, there was an association with an increased risk of newly developed chronic kidney disease.

  16. Preclinical dosimetry of magnetic fluid hyperthermia for bladder cancer

    Science.gov (United States)

    Oliveira, Tiago R.; Stauffer, Paul R.; Lee, Chen-Ting; Landon, Chelsea; Etienne, Wiguins; Maccarini, Paolo F.; Inman, Brant; Dewhirst, Mark W.

    2013-02-01

    Background Despite positive efficacy, thermotherapy is not widely used in clinical oncology. Difficulties associated with field penetration and controlling power deposition patterns in heterogeneous tissue have limited its use for heating deep in the body. Heat generation using iron-oxide super-paramagnetic nanoparticles excited with magnetic fields has been demonstrated to overcome some of these limitations. The objective of this preclinical study is to investigate the feasibility of treating bladder cancer with magnetic fluid hyperthermia (MFH) by analyzing the thermal dosimetry of nanoparticle heating in a rat bladder model. Methods The bladders of 25 female rats were injected with 0.4 ml of Actium Biosystems magnetite-based nanoparticles (Actium Biosystems, Boulder CO) via catheters inserted in the urethra. To assess the distribution of nanoparticles in the rat after injection we used the 7 T small animal MRI system (Bruker ClinScan, Bruker BioSpin MRI GmbH, Ettlingen, Germany). Heat treatments were performed with a small animal magnetic field applicator (Actium Biosystems, Boulder CO) with a goal of raising bladder temperature to 42°C in 1°C/min to a steady-state of 42°C. Conclusion Our data demonstrate that a MFH system provides well-localized heating of rat bladder with effective control of temperature in the bladder and minimal heating of surrounding tissues.

  17. The enhanced bladder cancer susceptibility of NAT2 slow acetylators towards aromatic amines: a review considering ethnic differences.

    Science.gov (United States)

    Golka, Klaus; Prior, Verena; Blaszkewicz, Meinolf; Bolt, Hermann M

    2002-03-10

    Human bladder cancer may be caused by exposure to aromatic amines. The polymorphic enzyme N-acetyltransferase 2 (NAT2) is involved in the metabolism of these compounds. Two classical studies on chemical workers in Europe, exposed in the past to aromatic amines like benzidine, unambiguously showed that the slow acetylator status is a genetic risk factor for arylamine-induced bladder cancer. In the former benzidine industry in Huddington, Great Britain, 22 of 23 exposed cases with bladder cancer, but only 57% of 95 local controls without bladder cancer were of the slow acetylator phenotype. In Leverkusen, Germany, 82% of 92 benzidine-exposed chemical workers with bladder cancer were of the slow acetylator phenotype, whereas only 48% of 331 chemical workers who had worked at that plant were of the slow acetylator phenotype. This is in line with several smaller studies, which also show an over-representation of the slow acetylator status in formerly arylamine-exposed subjects with bladder cancer. Some of these studies included also subjects that were exposed to aromatic amines by having applied dyes, paints and varnishes. These European findings are in contrast to a large study on Chinese workers occupationally exposed to aromatic amines. In this study, only five of 38 bladder cancer cases occupationally exposed to arylamines were of the slow acetylator genotype. This is much lower than the ratio of slow acetylators to the general population in China. This points to different mechanisms of susceptibility for bladder cancer upon exposure to aromatic amines between European (Caucasian) and Chinese populations.

  18. Allelic imbalance analysis using a single-nucleotide polymorphism microarray for the detection of bladder cancer recurrence.

    NARCIS (Netherlands)

    Coenen, M.J.H.; Ploeg, M.; Schijvenaars, M.M.V.A.P.; Cornel, E.B.; Karthaus, H.F.M.; Scheffer, H.; Witjes, J.A.M.; Franke, B.; Kiemeney, L.A.L.M.

    2008-01-01

    PURPOSE: Non-muscle-invasive bladder cancer is a frequently occurring cancer, with an extremely high recurrence risk. Recurrence detection is based on cytology and urethrocystoscopy. A previous study suggested that a single-nucleotide polymorphism (SNP) array may be effective for noninvasive detecti

  19. p53 Status correlates with the risk of recurrence in non-muscle invasive bladder cancers treated with Bacillus Calmette-Guerin: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xiaofeng Zhou

    Full Text Available Published studies have yielded inconsistent results on the relationship between p53 status and the prognosis of non-muscle invasive bladder cancer (NMIBC treated with Bacillus Calmette-Guérin (BCG intravesical therapy. Therefore, we performed a meta-analysis to evaluate the prognostic value of p53 in NMIBC treated with BCG.We systematically searched for relevant literature in PubMed, EMBASE, CNKI, and Chinese Wanfang databases. Hazard ratios (HRs with 95% confidence intervals (CIs were combined as the effect size (ES across studies for recurrence-free survival (RFS and progression-free survival (PFS.A total of 11 studies, consisting of 1,049 participants, met the criteria. Overall, there was no clear relationship between p53 status and RFS or PFS for NMIBC patients treated with BCG (HR: 1.40, 95% CI: 0.91-2.16; HR: 1.37, 95% CI: 0.90-2.09, respectively. Obvious heterogeneity was observed across the studies (I2 = 69.5%, P = 0.001; I2 = 44.7%, P = 0.081, respectively. In stratified analysis by region, p53 overexpression was a predictor of poor RFS in Asian populations (HR: 1.57, 95% CI: 1.08-2.27. In addition, after excluding the studies that possibly contributed to the heterogeneity by the Galbraith plot, the overall association for RFS became statistically significant (HR: 1.38 95% CI: 1.08-1.77 without evidence of heterogeneity (I2 = 0.0%, P = 0.499.This meta-analysis suggests that p53 overexpression in NMIBC patients treated with BCG may be associated with RFS, especially in Asian populations. Because of the heterogeneity and other limitations, further studies with rigid criteria and large populations are still warranted to confirm our findings.

  20. Social Awareness on Early Diagnosis and Treatment of Bladder Cancer: Importance of Age and Education

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    Doğan Değer

    2017-03-01

    Full Text Available Objective: We aimed to evaluate the recognition level of bladder cancer in the society by conducting a survey with regards to social awareness in early diagnosis of bladder cancer in this study. Materials and Methods: The survey was conducted on 100 randomly selected patients who were admitted to our clinic in May 2016 for any complaints. In the survey, the main focus was hematuria which is the first and the most common symptom of bladder cancer and questions and statements on this subject was used. Results: Of 100 patients, 67 (66.7% were male, and 33 (33.3% were female. Thirty six of the patients were younger than 50 (36%, and 64 of them (64% were 50 years and older. Education level of 40 (40% patients was found to be university level, and 60 (60% patients we high school graduates or lower. Twenty seven (27% patients had complains about blood in the urine, while 67 (67% of them had no such complaint. Of 27 patients that had complaint about hematuria, which is the most important symptom of bladder cancer 22 (81% were male and 5 (19% were female. We divided the patients into two groups based on 50 age limit. Group 1 included patients who were below 50, while the group 2 consisted of patients who were 50 years old and above. The rates of immediate consultation were determined to be significantly higher in group 2 than group 1. The rate of consulting urology department in the presence of hematuria, and the rates of considering the risk of bladder cancer as a possible diagnosis were higher in group 2, but the difference was not statistically significant. There was no significant difference found between the two groups who were separated by age in terms of required diagnostic tests. The patients were divided into two more groups based on their education level. Group 3 included patients of university graduates, and group 4 included patients with high school graduates or lower. The rates of immediate consultation were significantly higher in group 4

  1. Molecular targets in urothelial cancer: detection, treatment, and animal models of bladder cancer

    Science.gov (United States)

    Smolensky, Dmitriy; Rathore, Kusum; Cekanova, Maria

    2016-01-01

    Bladder cancer remains one of the most expensive cancers to treat in the United States due to the length of required treatment and degree of recurrence. In order to treat bladder cancer more effectively, targeted therapies are being investigated. In order to use targeted therapy in a patient, it is important to provide a genetic background of the patient. Recent advances in genome sequencing, as well as transcriptome analysis, have identified major pathway components altered in bladder cancer. The purpose of this review is to provide a broad background on bladder cancer, including its causes, diagnosis, stages, treatments, animal models, as well as signaling pathways in bladder cancer. The major focus is given to the PI3K/AKT pathway, p53/pRb signaling pathways, and the histone modification machinery. Because several promising immunological therapies are also emerging in the treatment of bladder cancer, focus is also given on general activation of the immune system for the treatment of bladder cancer. PMID:27784990

  2. The granulocyte macrophage–colony stimulating factor surface modified MB49 bladder cancer stem cells vaccine against metastatic bladder cancer

    Directory of Open Access Journals (Sweden)

    Yong-tong Zhu

    2014-07-01

    Full Text Available The MB49 bladder cancer cell vaccine was effective against bladder cancer in the mice model in previous studies. However, part of the tumors regrew as the vaccine could not eliminate the cancer stem cells (CSCs. MB49 bladder cancer stem cells (MCSCs were isolated by a combination of the limited dilution method and the serum free culture medium method. MCSCs possessed higher expression of CD133, CD44, OCT4, NANOG, and ABCG2, the ability of differentiation, higher proliferative abilities, lower susceptibility to chemotherapy, greater migration in vitro, and stronger tumorigenic abilities in vivo. Then streptavidin–mouse granulocyte macrophage–colony stimulating factor (SA–mGM–CSF MCSCs vaccine was prepared. SA–mGM–CSF MCSCs vaccine extended the survival of the mice and inhibited the growth of tumor in protective, therapeutic, memorial and specific immune response experiments. The level of immunoglobulin G and the ratio of dendritic cells and CD4+ and CD8+ T cells were highest in the experimental group when compared to those in other four control groups, as well as for the cytotoxicity assay. We demonstrated that SA–mGM–CSF MCSCs vaccine induces an antitumor immune response to metastatic bladder cancer.

  3. Identification of methylated genes associated with aggressive bladder cancer.

    Directory of Open Access Journals (Sweden)

    Carmen J Marsit

    Full Text Available Approximately 500,000 individuals diagnosed with bladder cancer in the U.S. require routine cystoscopic follow-up to monitor for disease recurrences or progression, resulting in over $2 billion in annual expenditures. Identification of new diagnostic and monitoring strategies are clearly needed, and markers related to DNA methylation alterations hold great promise due to their stability, objective measurement, and known associations with the disease and with its clinical features. To identify novel epigenetic markers of aggressive bladder cancer, we utilized a high-throughput DNA methylation bead-array in two distinct population-based series of incident bladder cancer (n = 73 and n = 264, respectively. We then validated the association between methylation of these candidate loci with tumor grade in a third population (n = 245 through bisulfite pyrosequencing of candidate loci. Array based analyses identified 5 loci for further confirmation with bisulfite pyrosequencing. We identified and confirmed that increased promoter methylation of HOXB2 is significantly and independently associated with invasive bladder cancer and methylation of HOXB2, KRT13 and FRZB together significantly predict high-grade non-invasive disease. Methylation of these genes may be useful as clinical markers of the disease and may point to genes and pathways worthy of additional examination as novel targets for therapeutic treatment.

  4. Status of integrated irradiation and cystectomy for bladder cancer.

    Science.gov (United States)

    Whitmore, W F; Batata, M

    1984-11-01

    The rationale and representative results of integrated irradiation and cystectomy for bladder cancer are reviewed and an hypothesis regarding the mechanism and benefits of such treatment formulated. The basis for uncertainty regarding the value of preoperative irradiation is outlined and a perspective on the resolution of this uncertainty provided.

  5. Bladder cancer: epidemiology, staging and grading, and diagnosis.

    NARCIS (Netherlands)

    Kirkali, Z.; Chan, T.; Manoharan, M.; Algaba, F.; Busch, C.; Cheng, L.; Kiemeney, L.A.L.M.; Kriegmair, M.; Montironi, R.; Murphy, W.M.; Sesterhenn, I.A.; Tachibana, M.; Weider, J.

    2005-01-01

    Bladder cancer is a heterogeneous disease with a variable natural history. At one end of the spectrum, low-grade Ta tumors have a low progression rate and require initial endoscopic treatment and surveillance but rarely present a threat to the patient. At the other extreme, high-grade tumors have a

  6. Genomic Alterations in Liquid Biopsies from Patients with Bladder Cancer

    DEFF Research Database (Denmark)

    Birkenkamp-Demtröder, Karin; Nordentoft, Iver Kristiansen; Christensen, Emil;

    2016-01-01

    Background: At least half of the patients diagnosed with non–muscle-invasive bladder cancer (NMIBC) experience recurrence and approximately 15% will develop progression to muscle invasive or metastatic disease. Biomarkers for disease surveillance are urgently needed. Objective: Development of ass...

  7. BCG and the treatment of superficial bladder cancer.

    Science.gov (United States)

    Moss, J T; Kadmon, D

    1991-12-01

    In this report, we review the evolution of bacillus Calmette-Guérin (BCG) immunotherapy as a legitimate form of treatment in superficial, nonmuscle-invasive bladder cancer. In the US, an estimated 45,000 new cases of bladder cancer are diagnosed each year and the annual death rate approaches 11,000. Approximately 70 percent of these cancers are superficial at the time of initial presentation. The treatment of superficial bladder cancer has three objectives: (1) eradication of existing disease, (2) prophylaxis against tumor recurrence, and (3) prevention of tumor progression (either muscular invasion, metastatic spread, or both). Cystectomy generally is reserved for muscle-invasive disease. Transurethral resection of the bladder tumor is the preferred initial therapy. Intravesical instillations of various chemotherapeutic agents following transurethral resection have been extensively investigated. Some of the common agents used include thiotepa, mitomycin, and doxorubicin. Despite such treatment efforts, however, over 40 percent of patients with superficial bladder cancer experience a recurrence of their tumor within three years. Approximately half of these recurrences either present as less-well-differentiated tumors or have already penetrated into the bladder musculature, metastasized, or both. Since Morales et al. first introduced intravesical BCG vaccine for prophylaxis as well as for treatment of superficial bladder tumors in 1976, support has grown rapidly for its use as an alternative to chemotherapy. When used with prophylactic intent following transurethral resection, recurrence rates are lower than those achieved with other agents. In addition, BCG is emerging as the consensus drug of choice for treating carcinoma in situ of the bladder. The mechanisms by which BCG exerts its antitumor activity remain largely unknown. BCG is thought to stimulate a localized, nonspecific inflammatory response that leads to subsequent shedding of tumor cells. A large body

  8. Towards improved bladder cancer diagnosis using fluorescence imaging and Raman spectroscopy

    NARCIS (Netherlands)

    Grimbergen, M.C.M.

    2010-01-01

    Bladder cancer is the fourth most common type of cancer worldwide. Its high recurrence rate makes bladder cancer one of the most prevalent types of cancer in the western world and the most costly type of cancer over the patient’s lifetime. In the Netherlands, each year 5,400 new patients with bladde

  9. Magnetic resonance imaging of the urinary bladder: cancer staging and beyond

    Energy Technology Data Exchange (ETDEWEB)

    Haider, E.A. [McMaster Univ. Medical Centre, Dept. of Medical Imaging, Hamilton, Ontario (Canada); Jhaveri, K.S.; O' Malley, M.E.; Haider, M.A. [Univ. of Toronto, Dept. of Medical Imaging, Univ. Health Network and Mount Sinai Hospital, Toronto, Ontario (Canada)], E-mail: Kartik.Jhaveri@uhn.on.ca; Jewett, M.A.; Rendon, R.A. [Univ. of Toronto, Dept. of Urology Univ. Health Network, Toronto, Ontario (Canada)

    2008-12-15

    Magnetic resonance imaging (MRI) is a promising technique for imaging bladder tumours. It offers distinct benefits over other imaging modalities owing to its superior contrast, spatial resolution, multiplanar capabilities, and the availability of a nonnephrotoxic contrast agent. The main indication for MRI of the urinary bladder is local staging of bladder cancers. MRI may also be used to evaluate undiagnosed bladder lesions. In some cases MRI may play an important role in early detection and characterizing of certain bladder lesions. This article provides an overview of MRI's role in bladder imaging with emphasis on local tumour staging. MRI features of various urinary bladder lesions are described. (author)

  10. DNA methylation profiles delineate etiologic heterogeneity and clinically important subgroups of bladder cancer.

    Science.gov (United States)

    Wilhelm-Benartzi, C S; Koestler, D C; Houseman, E A; Christensen, B C; Wiencke, John K; Schned, A R; Karagas, M R; Kelsey, K T; Marsit, C J

    2010-11-01

    DNA methylation profiles can be used to define molecular cancer subtypes that may better inform disease etiology and clinical decision-making. This investigation aimed to create DNA methylation profiles of bladder cancer based on CpG methylation from almost 800 cancer-related genes and to then examine the relationship of those profiles with exposures related to risk and clinical characteristics. DNA, derived from formalin-fixed paraffin-embedded tumor samples obtained from incident cases involved in a population-based case-control study of bladder cancer in New Hampshire, was used for methylation profiling on the Illumina GoldenGate Methylation Bead Array. Unsupervised clustering of those loci with the greatest change in methylation between tumor and non-diseased tissue was performed to defined molecular subgroups of disease, and univariate tests of association followed by multinomial logistic regression was used to examine the association between these classes, bladder cancer risk factors and clinical phenotypes. Membership in the two most methylated classes was significantly associated with invasive disease (P class 3 and 4). Male gender (P = 0.04) and age >70 years (P = 0.05) was associated with membership in one of the most methylated classes. Finally, average water arsenic levels in the highest percentile predicted membership in an intermediately methylated class of tumors (P = 0.02 for both classes). Exposures and demographic associated with increased risk of bladder cancer specifically associate with particular subgroups of tumors defined by DNA methylation profiling and these subgroups may define more aggressive disease.

  11. Role of Sonic Hedgehog (Shh) Signaling in Bladder Cancer Stemness and Tumorigenesis.

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    Syed, Islam S; Pedram, Akbari; Farhat, Walid A

    2016-02-01

    Sonic hedgehog (Shh) signaling pathway has emerged as a critical component of bladder development, cancer initiation, and progression. While the role of Shh signaling in bladder development is well documented, its role in bladder cancer progression is uncertain. Additionally, epithelial-to-mesenchymal transition (EMT) has been identified to promote bladder cancer progression in the initial stages and also contribute to drug resistance in the later stage and ultimately metastasis. We speculate that epithelial-to-mesenchymal transitions (EMT) and Shh fuel the carcinogenesis process. This review presents the most recent studies focusing on the role of Shh signaling in bladder cancer progression.

  12. PHOTODYNAMIC DIAGNOSIS AND FLUORESCENCE SPECTROSCOPY IN SUPERFICIAL BLADDER CANCER

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    I. G. Rusakov

    2009-01-01

    Full Text Available A comprehensive fluorescence technique has been developed to study the urinary bladder mucosa in patients with superficial bladder cancer (BC, by using alasense, white light cystoscopy, fluorescence cytoscopy, and local fluorescence spectroscopy in vivo. Quantification of urothelium fluorescence in the red emission foci of 5-ALA-induced protophorphyrin, with the local autofluorescence intensity being borne in mind, has been shown to increase the specificity of photodynamic diagnosis of superficial BC from 70 to 85% (p ≤ 0.05 and the total accuracy of the technique from 80 to 86%.  

  13. Improvement of the cytological diagnosis of bladder cancer

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    M. G. Leonov

    2014-12-01

    Full Text Available The paper gives the comparative results of cytological examination of alcohol-induced bladder washouts by liquid-based cytology and conventional cytology in 323 patients, including 150 with suspected bladder cancer (BC and 173 patients after performed combination or combined treatment for BC. The performed investigation has established that the diagnostic value of liquid-based cytology in diagnosing BC and its local recurrences is 1.3-fold higher than that of conventional cytology.

  14. Do Standardised Prognostic Algorithms Reflect Local Practice? Application of EORTC Risk Tables for Non-Muscle Invasive (pTa/pT1 Bladder Cancer Recurrence and Progression in a Local Cohort

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    Rajiv Pillai

    2011-01-01

    Full Text Available A risk calculator algorithm to allow prediction of probabilities of 1- and 5-year recurrence and progression rates in individuals with pTa/pT1 bladder cancer has been proposed by the European Organisation for Research and Treatment of Cancer (EORTC and was incorporated into the European Association of Urology guidelines in 2006. We attempted to validate this algorithm in a cohort of patients with known outcome. Prognostic data were collected from a consecutively presenting cohort of 109 patients with non-muscle invasive (pTa/pT1 transitional cell cancer (TCC at a single institution between 1983 and 1985. Using the same statistical models as in the EORTC original paper, predicted probabilities of 1- and 5-year recurrence and progression were calculated. Patients were divided into four risk groups for recurrence (Ir-IVr and progression (Ip-IVp, respectively, using six prognostic criteria. These were then compared to the probabilities predicted in the EORTC algorithm. The predicted 1- and 5-year probabilities of recurrence were significantly higher in the study population as compared to the original EORTC algorithm for all four risk groups. The predicted 1-year probabilities for progression in groups Ip/IIIp and at 5-years for groups Ip/IIp were in accordance with the original algorithm, but were higher for the other progression groups. The concordance for the model of prediction using the study group for recurrence at 1 and 5 years was 62 and 63%, respectively, and for progression was 65 and 67, respectively. We were unable to validate the proposed algorithm in our group of patients. Although our study has limitations that prevent firm conclusions on the validity of the algorithm, it does expose some of the drawbacks of standardised nomograms when applied to local clinical practice.

  15. Bladder Cancer in an Inguinoscrotal Vesical Hernia

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    Lucas Regis

    2012-01-01

    Full Text Available We present the case of a 79-year-old male who, due to hematuria, underwent cystoscopy that showed a lesion in the bladder dome. Transurethral resection was attempted, but access to the tumor by this route was impossible. Given the findings, a body CT scan was performed showing an inguinoscrotal hernia with vesical carcinoma contained. Open surgical treatment of the vesical carcinoma contained within the inguinoscrotal hernia was performed in conjunction with the hernia repair. The anatomical pathology report confirmed a high-grade urothelial carcinoma (stage pT2b with a free resection margin of <1 mm. Adjuvant radiotherapy was selected for subsequent treatment. The presence of bladder tumor in an inguinoscrotal hernia is an uncommon finding and a diagnostic delay can be assumed. The initial therapeutic plan may need to be changed from the usual approaches due to the atypical presentation.

  16. A microRNA-7 binding site polymorphism in HOXB5 leads to differential gene expression in bladder cancer.

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    Junhua Luo

    Full Text Available PURPOSE: To investigate the biological function of HOXB5 in human bladder cancer and explore whether the HOXB5 3'-UTR SNP (1010A/G, which is located within the microRNA-7 binding site, was correlated with clinical features of bladder cancer. METHODS: Expression of HOXB5 in 35 human bladder cancer tissues and 8 cell lines were examined using real-time PCR and immunohistochemistry. Next, we explored the biological function of HOXB5 in vitro using cell proliferation, migration and colony formation assays. Using bioinformatics, a SNP (1010A/G was found located within the microRNA-7 binding site in the 3'-UTR of HOXB5. Real-time PCR was used to test HOXB5 expression affected by different alleles. Finally, multivariate logistic regression analysis was used to determine the relationship between SNP (1010A/G frequency and clinical features in 391 cases. RESULTS: HOXB5 was frequently over-expressed both in bladder cancer tissues and cell lines. Inhibition of HOXB5 suppressed the oncogenic function of cancer cells. Next, we demonstrated that a SNP (1010A/G, located within the microRNA-7 binding site in the 3'-UTR of HOXB5, could affect HOXB5 expression in bladder cancer mainly by differential binding activity of microRNA-7 and SNP-related mRNA stability. Finally, we also showed the frequency of 1010G genotype was higher in cancer group compared to normal controls and correlated with the risk of high grade and high stage. CONCLUSION: HOXB5 is overexpressed in bladder cancer. A miRNA-binding SNP (1010A/G located within 3'-UTR of HOXB5 is associated with gene expression and may be a promising prognostic factor for bladder cancer.

  17. Scoring system development for prediction of extravesical bladder cancer

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    Prelević Rade

    2014-01-01

    Full Text Available Background/Aim. Staging of bladder cancer is crucial for optimal management of the disease. However, clinical staging is not perfectly accurate. The aim of this study was to derive a simple scoring system in prediction of pathological advanced muscle-invasive bladder cancer (MIBC. Methods. Logistic regression and bootstrap methods were used to create an integer score for estimating the risk in prediction of pathological advanced MIBC using precystectomy clinicopathological data: demographic, initial transurethral resection (TUR [grade, stage, multiplicity of tumors, lymphovascular invasion (LVI], hydronephrosis, abdominal and pelvic CT radiography (size of the tumor, tumor base width, and pathological stage after radical cystectomy (RC. Advanced MIBC in surgical specimen was defined as pT3-4 tumor. Receiving operating characteristic (ROC curve quantified the area under curve (AUC as predictive accuracy. Clinical usefulness was assessed by using decision curve analysis. Results. This single-center retrospective study included 233 adult patients with BC undergoing RC at the Military Medical Academy, Belgrade. Organ confined disease was observed in 101 (43.3% patients, and 132 (56.7% had advanced MIBC. In multivariable analysis, 3 risk factors most strongly associated with advanced MIBC: grade of initial TUR [odds ratio (OR = 4.7], LVI (OR = 2, and hydronephrosis (OR = 3.9. The resultant total possible score ranged from 0 to 15, with the cut-off value of > 8 points, the AUC was 0.795, showing good discriminatory ability. The model showed excellent calibration. Decision curve analysis showed a net benefit across all threshold probabilities and clinical usefulness of the model. Conclusion. We developed a unique scoring system which could assist in predicting advanced MIBC in patients before RC. The scoring system showed good performance characteristics and introducing of such a tool into daily clinical decision-making may lead to more appropriate

  18. Multiplex PCR and Next Generation Sequencing for the Non-Invasive Detection of Bladder Cancer.

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    Douglas G Ward

    Full Text Available Highly sensitive and specific urine-based tests to detect either primary or recurrent bladder cancer have proved elusive to date. Our ever increasing knowledge of the genomic aberrations in bladder cancer should enable the development of such tests based on urinary DNA.DNA was extracted from urine cell pellets and PCR used to amplify the regions of the TERT promoter and coding regions of FGFR3, PIK3CA, TP53, HRAS, KDM6A and RXRA which are frequently mutated in bladder cancer. The PCR products were barcoded, pooled and paired-end 2 x 250 bp sequencing performed on an Illumina MiSeq. Urinary DNA was analysed from 20 non-cancer controls, 120 primary bladder cancer patients (41 pTa, 40 pT1, 39 pT2+ and 91 bladder cancer patients post-TURBT (89 cancer-free.Despite the small quantities of DNA extracted from some urine cell pellets, 96% of the samples yielded mean read depths >500. Analysing only previously reported point mutations, TERT mutations were found in 55% of patients with bladder cancer (independent of stage, FGFR3 mutations in 30% of patients with bladder cancer, PIK3CA in 14% and TP53 mutations in 12% of patients with bladder cancer. Overall, these previously reported bladder cancer mutations were detected in 86 out of 122 bladder cancer patients (70% sensitivity and in only 3 out of 109 patients with no detectable bladder cancer (97% specificity.This simple, cost-effective approach could be used for the non-invasive surveillance of patients with non-muscle-invasive bladder cancers harbouring these mutations. The method has a low DNA input requirement and can detect low levels of mutant DNA in a large excess of normal DNA. These genes represent a minimal biomarker panel to which extra markers could be added to develop a highly sensitive diagnostic test for bladder cancer.

  19. Re-examination of the Natural History of High-grade T1 Bladder Cancer using a Large Contemporary Cohort

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    Daniel J. Canter

    2014-04-01

    Full Text Available IntroductionHigh-grade T1 (HGT1 bladder cancer represents a clinical challenge in that the urologist must balance the risk of disease progression against the morbidity and potential mortality of early radical cystectomy and urinary diversion. Using two non-muscle invasive bladder cancer (NMIBC databases, we re-examined the rate of progression of HG T1 bladder cancer in our bladder cancer populations.Materials and MethodsWe queried the NMIBC databases that have been established independently at the Atlanta Veterans Affairs Medical Center (AVAMC and the University of Pennsylvania to identify patients initially diagnosed with HGT1 bladder cancer. Demographic, clinical, and pathologic variables were examined as well as rates of recurrence and progression.ResultsA total of 222 patients were identified; 198 (89.1% and 199 (89.6% of whom were male and non-African American, respectively. Mean patient age was 66.5 years. 191 (86.0% of the patients presented with isolated HG T1 disease while 31 (14.0% patients presented with HGT1 disease and CIS. Induction BCG was utilized in 175 (78.8% patients. Recurrence occurred in 112 (50.5% patients with progression occurring in only 19 (8.6% patients. At a mean follow-up of 51 months, overall survival was 76.6%. Fifty two patients died, of whom only 13 (25% patient deaths were bladder cancer related.ConclusionsIn our large cohort of patients, we found that the risk of progression at approximately four years was only 8.6%. While limited by its retrospective nature, this study could potentially serve as a starting point in re-examining the treatment algorithm for patients with HG T1 bladder cancer.

  20. A contribution to improved radiotherapy for muscle invading urinary bladder cancer

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    Muren, Ludvig PAul

    2002-07-01

    Cystectomy has traditionally been regarded the treatment of choice for muscle invading urinary bladder cancer in most countries. Radiotherapy has been offered patients considered unfit for cystectomy. Since the contraindications of surgery are frequent among bladder cancer patients, a substantial amount of patients with muscle invading bladder cancer (typically 50%) are still managed primarily with radiation. Recently, a tri-modality, organsparing treatment (trans-urethral resection and radio-chemotherapy) has been proposed for bladder cancer, like in the management of a range of other common malignancies. This approach may provide as high control rates as cystectomy yet maintain a higher quality of life for selected patient groups. In both the radical radiotherapy and the combined modality approach, high radiation doses are needed to improve local disease control. Radiation dose escalation requires improved conformation of dose distributions. This PhD programme aimed to develop improved conformal radiotherapy procedures in the management of patients with muscle invading urinary bladder cancer. In the initial phase of this work, computer-controlled movement of the linear accelerator collimator jaws during beam delivery was applied to shape so-called partially wedged beams (PWBs), that were designed specifically to tailor the dose distribution in bladder irradiation closer to the defined bladder target. The dosimetric verification and treatment planning implementation of this beam delivery concept were addressed, and we documented that these dynamic beams were delivered as accurately as standard beams. Particular attention was given to the BMS-96 diode array system, as it was adapted to dynamic beam dosimetry. Next, the potential clinical impact of these beams was analysed. In a retrospectively study of a set of urinary bladder treatment plans, the PWBs were seen to improve the dose homogeneity inside the bladder target as well as to reduce normal tissue (small

  1. Tumor-Associated Macrophages Provide Significant Prognostic Information in Urothelial Bladder Cancer.

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    Minna M Boström

    Full Text Available Inflammation is an important feature of carcinogenesis. Tumor-associated macrophages (TAMs can be associated with either poor or improved prognosis, depending on their properties and polarization. Current knowledge of the prognostic significance of TAMs in bladder cancer is limited and was investigated in this study. We analyzed 184 urothelial bladder cancer patients undergoing transurethral resection of a bladder tumor or radical cystectomy. CD68 (pan-macrophage marker, MAC387 (polarized towards type 1 macrophages, and CLEVER-1/Stabilin-1 (type 2 macrophages and lymphatic/blood vessels were detected immunohistochemically. The median follow-up time was 6.0 years. High macrophage counts associated with a higher pT category and grade. Among patients undergoing transurethral resection, all studied markers apart from CLEVER-1/Stabilin-1 were associated with increased risk of progression and poorer disease-specific and overall survival in univariate analyses. High levels of two macrophage markers (CD68/MAC387+/+ or CD68/CLEVER-1+/+ groups had an independent prognostic role after transurethral resection in multivariate analyses. In the cystectomy cohort, MAC387, alone and in combination with CD68, was associated with poorer survival in univariate analyses, but none of the markers were independent predictors of outcome in multivariate analyses. In conclusion, this study demonstrates that macrophage phenotypes provide significant independent prognostic information, particularly in bladder cancers undergoing transurethral resection.

  2. Bladder Carcinoma Data with Clinical Risk Factors and Molecular Markers: A Cluster Analysis

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    Enrique Redondo-Gonzalez

    2015-01-01

    Full Text Available Bladder cancer occurs in the epithelial lining of the urinary bladder and is amongst the most common types of cancer in humans, killing thousands of people a year. This paper is based on the hypothesis that the use of clinical and histopathological data together with information about the concentration of various molecular markers in patients is useful for the prediction of outcomes and the design of treatments of nonmuscle invasive bladder carcinoma (NMIBC. A population of 45 patients with a new diagnosis of NMIBC was selected. Patients with benign prostatic hyperplasia (BPH, muscle invasive bladder carcinoma (MIBC, carcinoma in situ (CIS, and NMIBC recurrent tumors were not included due to their different clinical behavior. Clinical history was obtained by means of anamnesis and physical examination, and preoperative imaging and urine cytology were carried out for all patients. Then, patients underwent conventional transurethral resection (TURBT and some proteomic analyses quantified the biomarkers (p53, neu, and EGFR. A postoperative follow-up was performed to detect relapse and progression. Clusterings were performed to find groups with clinical, molecular markers, histopathological prognostic factors, and statistics about recurrence, progression, and overall survival of patients with NMIBC. Four groups were found according to tumor sizes, risk of relapse or progression, and biological behavior. Outlier patients were also detected and categorized according to their clinical characters and biological behavior.

  3. Laparoscopic partial cystectomy for urachal and bladder cancer

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    Jose R. Colombo Jr.

    2008-01-01

    Full Text Available PURPOSE: To report our initial experiences with laparoscopic partial cystectomy for urachal and bladder malignancy. MATERIALS AND METHODS: Between March 2002 and October 2004, laparoscopic partial cystectomy was performed in 6 cases at 3 institutions; 3 cases were urachal adenocarcinomas and the remaining 3 cases were bladder transitional cell carcinomas. All patients were male, with a median age of 55 years (45-72 years. Gross hematuria was the presenting symptom in all patients, and diagnosis was established with trans-urethral resection bladder tumor in 2 patients and by means of cystoscopic biopsy in the remaining 4 patients. Laparoscopic partial cystectomy was performed using the transperitoneal approach under cystoscopic guidance. In each case, the surgical specimen was removed intact entrapped in an impermeable bag. One patient with para-ureteral diverticulum transitional cell carcinoma required concomitant ureteral reimplantation. RESULTS: All six procedures were completed laparoscopically without open conversion. The median operating time was 110 minutes (90-220 with a median estimated blood loss of 70 mL (50-100. Frozen section evaluations of bladder margins were routinely obtained and were negative for cancer in all cases. The median hospital stay was 2.5 days (2-4 and the duration of catheterization was 7 days. There were no intraoperative or postoperative complications. Final histopathology confirmed urachal adenocarcinoma in 3 cases and bladder transitional cell carcinoma in 3 cases. At a median follow-up of 28.5 months (range: 26 to 44 months, there was no evidence of recurrent disease as evidenced by radiologic or cystoscopic evaluation. CONCLUSIONS: Laparoscopic partial cystectomy in carefully selected patients with urachal and bladder cancer is feasible and safe, offering a promising and minimally invasive alternative for these patients.

  4. Bladder Cancer Stem-Like Cells: Their Origin and Therapeutic Perspectives

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    Tomokazu Ohishi

    2015-12-01

    Full Text Available Bladder cancer (BC, the most common cancer arising from the human urinary tract, consists of two major clinicopathological phenotypes: muscle-invasive bladder cancer (MIBC and non-muscle-invasive bladder cancer (NMIBC. MIBC frequently metastasizes and is associated with an unfavorable prognosis. A certain proportion of patients with metastatic BC can achieve a remission with systemic chemotherapy; however, the disease relapses in most cases. Evidence suggests that MIBC comprises a small population of cancer stem cells (CSCs, which may be resistant to these treatments and may be able to form new tumors in the bladder or other organs. Therefore, the unambiguous identification of bladder CSCs and the development of targeted therapies are urgently needed. Nevertheless, it remains unclear where bladder CSCs originate and how they are generated. We review recent studies on bladder CSCs, specifically focusing on their proposed origin and the possible therapeutic options based on the CSC theory.

  5. [Present aspects and problems regarding occupational bladder cancer due to exposure to aromatic amines].

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    Yamamura, J

    1989-12-01

    About a century has passed since the first case of bladder cancer due to occupational exposure to carcinogenic aromatic amines was reported. In the major developed countries of the world, it is forbidden to manufacture and/or to use such aromatic amines. In Japan in the 1950's, many workers were exposed to carcinogenic aromatic amines, but in 1972, the Labor Safety and Health Act came into force and manufacturing and/or using of four kinds of aromatic amines were forbidden. Recently it has been reported that the risk of bladder cancer in workers exposed to aromatic amines before the ban of these chemicals is approximately from several times to a hundred times compared with the general population, and some reports say that dose-response relationship was observed. The important issues now are the carcinogenicity of other kinds of aromatic amines besides benzidine and 2-naphthylamine, carcinogenicity of metabolites of several substances like synthetic dyes, and carcinogenic aromatic amines as impurities in substances imported from developing countries. The type of exposure to these carcinogens changes low level and long period exposures. In addition to the chemical or dye industries, an increased risk of bladder cancer was observed among workers handling leather and rubber and those engaged in printing, textile industries, hairdressing, truck driving and so on. In the future, it will be necessary to cooperate with the departments of epidemiology, toxicology and clinical medicine for the purpose of estimating the risk of these occupations and the health care administration of the exposed workers.

  6. Orthotopic ileal neobladder reconstruction for bladder cancer: is adjuvant chemotherapy safe?

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    Murugesan Manoharan

    2006-10-01

    Full Text Available OBJECTIVE: We examined our database of patients undergoing radical cystectomy (RC with orthotopic neobladder (NB to determine whether adjuvant chemotherapy in this group is safe. MATERIALS AND METHODS: We performed a retrospective analysis of patients who underwent radical cystectomy and urinary diversion between 1992 and 2004. Relevant clinical and therapeutic data were entered into a database. High-risk bladder cancer patients who underwent NB were identified. They were stratified into 2 groups, those who received adjuvant chemotherapy and those who did not. The incidence of complications between the 2 groups was analyzed and compared. RESULTS: Over the 12-year period, 136 patients underwent RC and NB construction for bladder cancer. Of these, 83 patients were at high risk for recurrence. Nineteen patients received adjuvant chemotherapy and 64 did not. The complication rate in the adjuvant chemotherapy group was 53% and it was 23% in those who did not receive chemotherapy. There were no perioperative or treatment related death. There were 2 patients with grade 4 toxicity in the adjuvant chemotherapy group. There was a statistical difference between these two groups with regard to the incidence of complications. However, none of these complications was life-threatening, required only conservative treatment and caused no long-term disability. CONCLUSIONS: Adjuvant chemotherapy is a safe treatment for patients undergoing RC and NB substitution. Hence, the option of orthotopic NB should not be denied in selected bladder cancer patients with high risk for recurrent disease.

  7. Elevated bladder cancer in northern New England: The role of drinking water and arsenic

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    Baris, Dalsu; Wadell, Richard; Freeman, Laura; Schwenn, Molly; Colt, Joanne; Ayotte, Joseph; Ward, Mary; Nuckols, John; Schned, Alan; Jackson, Brian; Clerkin, Castine; Rothman, Nathanial; Moore, Lee; Taylor, Anne; Robinson, Gilpin; Hosain, Monawar G.; Armenti, Carla; McCoy, Richard; Samanic, Claudine; Hoover, Robert; Fraumeni, Joseph; Johnson, Alison; Karagas, Margaret; Silverman, Debra

    2016-01-01

    Background: Bladder cancer mortality rates have been elevated in northern New England for at least five decades. Incidence rates in Maine, New Hampshire, and Vermont are about 20% higher than the United States overall. We explored reasons for this excess, focusing on arsenic in drinking water from private wells, which are particularly prevalent in the region.Methods: In a population-based case-control study in these three states, 1213 bladder cancer case patients and 1418 control subjects provided information on suspected risk factors. Log transformed arsenic concentrations were estimated by linear regression based on measurements in water samples from current and past homes. All statistical tests were two-sided.Results: Bladder cancer risk increased with increasing water intake ( Ptrend = .003). This trend was statistically significant among participants with a history of private well use ( Ptrend = .01). Among private well users, this trend was apparent if well water was derived exclusively from shallow dug wells (which are vulnerable to contamination from manmade sources, Ptrend = .002) but not if well water was supplied only by deeper drilled wells ( Ptrend = .48). If dug wells were used pre-1960, when arsenical pesticides were widely used in the region, heavier water consumers (>2.2 L/day) had double the risk of light users (<1.1 L/day, Ptrend = .01). Among all participants, cumulative arsenic exposure from all water sources, lagged 40 years, yielded a positive risk gradient ( Ptrend = .004); among the highest-exposed participants (97.5th percentile), risk was twice that of the lowest-exposure quartile (odds ratio = 2.24, 95% confidence interval = 1.29 to 3.89).Conclusions: Our findings support an association between low-to-moderate levels of arsenic in drinking water and bladder cancer risk in New England. In addition, historical consumption of water from private wells, particularly dug wells in an era when arsenical pesticides were widely used, was

  8. Association of genetic polymorphism of glutathione S-transferase (GSTM1, GSTT1, GSTP1) with bladder cancer susceptibility.

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    Safarinejad, Mohammad Reza; Safarinejad, Saba; Shafiei, Nayyer; Safarinejad, Shiva

    2013-10-01

    The glutathione-S-transferases (GSTs) comprise a class of enzymes that detoxify carcinogenic compounds by conjugating glutathione to facilitate their removal. Polymorphisms in GSTM1, GSTT1, and GSTP1 genes have been related to risk for bladder cancer. Studies focusing on GSTs gene variants relationship with the risk of bladder cancer have produced conflicting and inconsistent results. We examine the association between genetic polymorphism of glutathione S-transferase P1, GSTM1, GSTT1 genes and development of bladder transitional cell carcinoma (TCC). The study population consisted of 166 histologically confirmed male bladder TCC cases and 332 healthy male controls. Genotyping was done using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method and also investigated combined gene interactions. The GSTP1 Val/Val genotype was significantly associated with bladder cancer (OR = 4.32, 95% CI: 2.64-6.34), whereas the association observed for GSTM1 null (OR = 1.32, 95% CI: 0.82-2.62; P = 0.67) and GSTT1 null genotype (OR = 1.18, 95% CI: 0.79-1.67; P = 0.74) did not reach statistical significance. There was a significant multiple interaction between GSTM1, GSTT1, and GSTP1 genotypes in risk of bladder cancer (P for interaction = 0.02). The risk associated with the concurrent presence of GSTM1 positive and GSTP1 Ile/Val or Val/Val (OR = 3.71, 95% CI: 2.34-5.54) and GSTT1 positive and GSTP1 Ile/Val or Val/Val (OR = 2.66, 95% CI: 1.54-4.72) was statistically significant. Patients carrying GSTP1 Val/Val genotype were at increased risk for developing high-grade (OR = 7.68, 95% CI: 4.73-19.25) and muscle invasive (OR = 10.67, 95% CI: 6.34-21.75) bladder cancer. High risk for bladder TCC also was observed with respect to combined GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 4.76, 95% CI: 2.68-18.72) and GSTM1 null/GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 6.42, 95% CI: 4.76-14.72) genotype variant. This study suggests that the GSTP1 polymorphism

  9. Organic cation secretion by Cancer borealis urinary bladder

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    Miller, D.S.; Holliday, C.W.

    1987-01-01

    In the crab, Cancer borealis, initial clearance studies showed a potent renal excretory system for the model organic cation, tetraethylammonium (TEA). (/sup 14/C)-TEA clearance averaged 145 +/- 32 ml/day, which was 18 times the paired polyethylene glycol clearance. TEA uptake by slices of urinary bladder was concentrative, saturable, inhibitable by N/sup 1/-methylnicotinamide chloride, and dependent on glycolytic, but not oxidative, metabolism. When mounted in flux chambers, bladders exhibited a large net secretory flux. For 0.1 mM TEA, the ratio of secretory to reabsorptive fluxes was 65. Urinary bladders from another crab, Cancer irroratus, and a lobster, Homarus americanus, also exhibited net TEA secretion. In C. borealis bladder, secretory transport was concentrative, saturable, and nearly abolished by addition of 1 mM quinine to the serosol bath. Reabsorptive transport was not concentrative and was not reduced by luminal quinine. The data are consistent with a secretory pathway that is transcellular and mediated by carriers at both the serosal and luminal membranes.

  10. The Antidiabetic Drug Metformin Inhibits the Proliferation of Bladder Cancer Cells in Vitro and in Vivo

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    Tao Zhang

    2013-12-01

    Full Text Available Recent studies suggest that metformin, a widely used antidiabetic agent, may reduce cancer risk and improve prognosis of certain malignancies. However, the mechanisms for the anti-cancer effects of metformin remain uncertain. In this study, we investigated the effects of metformin on human bladder cancer cells and the underlying mechanisms. Metformin significantly inhibited the proliferation and colony formation of 5637 and T24 cells in vitro; specifically, metformin induced an apparent cell cycle arrest in G0/G1 phases, accompanied by a strong decrease of cyclin D1, cyclin-dependent kinase 4 (CDK4, E2F1 and an increase of p21waf-1. Further experiments revealed that metformin activated AMP-activated protein kinase (AMPK and suppressed mammalian target of rapamycin (mTOR, the central regulator of protein synthesis and cell growth. Moreover, daily treatment of metformin led to a substantial inhibition of tumor growth in a xenograft model with concomitant decrease in the expression of proliferating cell nuclear antigen (PCNA, cyclin D1 and p-mTOR. The in vitro and in vivo results demonstrate that metformin efficiently suppresses the proliferation of bladder cancer cells and suggest that metformin may be a potential therapeutic agent for the treatment of bladder cancer.

  11. Bladder Cancer Screening Among Diabetic Patients On Metformin Therapy In A West Africa Subregion

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    Ufuoma Miller Fakpor

    2016-10-01

    Full Text Available Objective: The use of certain medications among diabetic patients put them at risk of developing bladder cancer. This study was done to examine the effects of metformin therapy on the bladder of diabetic patients and to assess the correlation between the effects of metformin and its duration of therapy. Methods: A total of 150 diabetic patients were sampled using a cross sectional study design. 10-15mls of random urine samples were collected into sterile containers over a period of five weeks. Smears were prepared, fixed and stained using Papanicolaou staining method and examined under the microscope for cytological studies. Results: The probability of developing bladder cancer among diabetic patients on metformin therapy is 0% among participants of all categories: 99 females and 51 males partook in this study.  Peak age group (35.33% were between the ages of 51 to 60 years, least age group (4.67% were 80 years and above. Traders of food items and used clothes constituted the peak occupational group of 27.52%, with fishermen  as least occupation group(0.67%, age group 61 to 70 had the highest duration of therapy of (15.8%, the least duration of (4.625% was among age group 25 to 30 years, the group of 80years and above had a duration of (4.857%.  No inflammatory, degenerative, benign or malignant cells were observed among urine samples from diabetic patients on metformin. Conclusion: This study equips us with knowledge that metformin therapy has no direct influence on the development of cancer of the bladder among diabetic patients as observed through urine cytology. This is the first time such study is done in West Africa region. The clinical implication is that Metformin, the commonest prescribed oral hypoglycemic is safe when considering the carcinogenic effects of anti-diabetic drugs, unlike insulin and some other drugs which have carcinogenic potential.   Keywords: metformin; cancer; bladder; diabetes; therapy

  12. Genetic variation in Glutathione S-Transferase Omega-1, Arsenic Methyltransferase and Methylene-tetrahydrofolate Reductase, arsenic exposure and bladder cancer: a case–control study

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    Beebe-Dimmer Jennifer L

    2012-06-01

    Full Text Available Abstract Background Ingestion of groundwater with high concentrations of inorganic arsenic has been linked to adverse health outcomes, including bladder cancer, however studies have not consistently observed any elevation in risk at lower concentrations. Genetic variability in the metabolism and clearance of arsenic is an important consideration in any investigation of its potential health risks. Therefore, we examined the association between genes thought to play a role in the metabolism of arsenic and bladder cancer. Methods Single nucleotide polymorphisms (SNPs in GSTO-1, As3MT and MTHFR were genotyped using DNA from 219 bladder cancer cases and 273 controls participating in a case–control study in Southeastern Michigan and exposed to low to moderate ( Results While no single SNP in As3MT was significantly associated with bladder cancer overall, several SNPs were associated with bladder cancer among those exposed to higher arsenic levels. Individuals with one or more copies of the C allele in rs11191439 (the Met287Thr polymorphism had an elevated risk of bladder cancer (OR = 1.17; 95% CI = 1.04-1.32 per 1 μg/L increase in average exposure. However, no association was observed between average arsenic exposure and bladder cancer among TT homozygotes in the same SNP. Bladder cancer cases were also 60% less likely to be homozygotes for the A allele in rs1476413 in MTHFR compared to controls (OR = 0.40; 95% CI = 0.18-0.88. Conclusions Variation in As3MT and MTHFR is associated with bladder cancer among those exposed to relatively low concentrations of inorganic arsenic. Further investigation is warranted to confirm these findings.

  13. Characterization of Uptake and Internalization of Exosomes by Bladder Cancer Cells

    Directory of Open Access Journals (Sweden)

    Carrie A. Franzen

    2014-01-01

    Full Text Available Bladder tumors represent a special therapeutic challenge as they have a high recurrence rate requiring repeated interventions and may progress to invasive or metastatic disease. Exosomes carry proteins implicated in bladder cancer progression and have been implicated in bladder cancer cell survival. Here, we characterized exosome uptake and internalization by human bladder cancer cells using Amnis ImageStreamX, an image cytometer. Exosomes were isolated by ultracentrifugation from bladder cancer culture conditioned supernatant, labeled with PKH-26, and analyzed on the ImageStreamX with an internal standard added to determine concentration. Exosomes were cocultured with bladder cancer cells and analyzed for internalization. Using the IDEAS software, we determined exosome uptake based on the number of PKH-26+ spots and overall PKH-26 fluorescence intensity. Using unlabeled beads of a known concentration and size, we were able to determine concentrations of exosomes isolated from bladder cancer cells. We measured exosome uptake by recipient bladder cancer cells, and we demonstrated that uptake is dose and time dependent. Finally, we found that uptake is active and specific, which can be partially blocked by heparin treatment. The characterization of cellular uptake and internalization by bladder cancer cells may shed light on the role of exosomes on bladder cancer recurrence and progression.

  14. Bladder Metastasis of non-Small Cell Lung Cancer : an Unusual Cause of Hematuria

    NARCIS (Netherlands)

    Karatas, O. Faruk; Bayrak, Reyhan; Yildirim, M. Erol; Bayrak, Omer; Cimentepe, Ersin; Unal, Dogan

    2009-01-01

    Approximately 2% of bladder malignancies are metastatic. The lung cancer makes metastasis sporadically to the bladder. A-69-year-old female patient presented with a history of pain in kidneys, vomiting and hematuria. Cystoscopic examination of the patient revealed small bladder capacity and solitary

  15. Bladder cancer among workers in the textile industry: results of a Spanish case-control study.

    Science.gov (United States)

    Gonzales, C A; Riboli, E; Lopez-Abente, G

    1988-01-01

    This paper presents results from a case-control study carried out in the county of Mataro, Spain. The study was designed to investigate the possible causes of an unusually high mortality rate from bladder cancer in Mataro county as compared to Spain as a whole, and this report focuses on occupational exposures. The study is based on 57 cases who were hospitalized for or died from bladder cancer between 1978 and 1981. Two controls per case were matched for sex, age, residence, and date of either hospitalization or death. Information was collected on smoking, coffee drinking, and occupation. Occupational histories were then evaluated and coded blind by a group of occupational health physicians. Analyses were carried out by means of conditional logistic regression. Among a group of common occupational sectors, an increased risk for past employment in the textile industry (OR = 2.2; p = .038) was found. Further analyses indicated that the risk is particularly elevated (OR = 4.41; 95% confidence limits; 1.15-16.84) for subjects who worked in dyeing or printing and who were most probably exposed to azo-dyes. Exposure in the textile industry may be responsible for 16% of the bladder cancers in the Mataro area. A list of dyes commonly used in the Mataro textile industries was compiled and cross-checked with lists of substances tested or evaluated for carcinogenesis.

  16. Arthritis and iritis after BCG therapy for bladder cancer.

    Science.gov (United States)

    Price, G E

    1994-03-01

    A patient with preexisting inactive ankylosing spondylitis experienced a recurrence of back pain and his first episode of acute peripheral arthritis and iritis after a second course of treatment with BCG for bladder cancer. The occurrence of iritis after BCG therapy has not been reported. The recurrence of spondyloarthropathy and the new appearance of iritis may have been part of a generalized enhancement of immunological reactivity produced by the BCG.

  17. Treatment of Muscle-Invasive Bladder Cancer in Older Patients.

    Science.gov (United States)

    Skinner, Eila C

    2016-01-01

    Treatment of muscle-invasive bladder cancer in older patients is challenging. Definitive therapy of localized disease requires either surgery or radiation therapy, ideally combined with systemic chemotherapy. However, current population data suggest that less than half of patients older than age 70 are offered such treatments. We will review tools available to assess the fitness of older patients for surgery, alternatives, and tips for perioperative patient treatment.

  18. Organochlorine Pesticides Exposure and Bladder Cancer: Evaluation from a Gene-Environment Perspective in a Hospital-Based Case-Control Study in the Canary Islands (Spain).

    Science.gov (United States)

    Boada, L D; Henríquez-Hernández, L A; Zumbado, M; Almeida-González, M; Álvarez-León, E E; Navarro, P; Luzardo, O P

    2016-01-01

    The incidence of bladder cancer has increased significantly since the 1950s. Pesticide exposure has been linked with increasing bladder cancer incidence, although the evidence is inconclusive. However, most epidemiological studies did not evaluate the potential role played by the organochlorine pesticides, the most widely used pesticides in Western countries from the 1940s to the 1970s. Organochlorine pesticides were banned in the late 1970s because of their persistence in the environment and their carcinogenic and mutagenic effects. Organochlorine pesticides were employed in huge amounts in the Spanish archipelago of the Canary Islands; the authors, therefore, evaluated the role played by organochlorine pesticides exposure on bladder cancer. Serum levels of the most prevalent organochlorine pesticides used in the agriculture of these Islands (dichlorodiphenyltrichloroethane [p,p'-DDT], and its metabolites dichlorodiphenyldichloroethylene [p,p'-DDE] and dichlorodiphenyldichloroethane [p,p'-DDD], hexachlorobenzene, hexachlorocyclohexane isomers, aldrin, dieldrin, endrin, heptachlor, cis-chlordane, trans-chlordane, α- and β-endosulfan, endosulfan sulfate, methoxychlor, and mirex) were measured in 140 bladder cancer cases and 206 controls. GST-M1 and GST-T1 gene polymorphisms were genotyped by polymerase chain reaction (PCR)-based methods. These results showed that serum levels of organochlorine pesticides did not increase bladder cancer risk. On the contrary, total burden of hexachlorocyclohexanes was found to be negatively associated to bladder cancer (odds ratio [OR] = 0.929, 95% confidence interval [CI]: 0.865-0.997; P = .041). This effect disappeared when the distribution of the gluthathione S-transferase polymorphisms was introduced in the statistical model. These results indicate that organochlorine pesticides are not a risk factor for bladder cancer. However, these findings provide additional evidence of gene-environment interactions for organochlorine

  19. A bladder cancer microenvironment simulation system based on a microfluidic co-culture model

    OpenAIRE

    Liu, Peng-Fei; Cao, Yan-wei; Zhang, Shu-Dong; Zhao, Yang; Liu, Xiao-guang; Shi, Hao-qing; Hu, Ke-yao; Zhu, Guan-qun; Ma, Bo; Niu, Hai-Tao

    2015-01-01

    A tumor microenvironment may promote tumor metastasis and progression through the dynamic interplay between neoplastic cells and stromal cells. In this work, the most representative and significant stromal cells, fibroblasts, endothelial cells, and macrophages were used as vital component elements and combined with bladder cancer cells to construct a bladder cancer microenvironment simulation system. This is the first report to explore bladder cancer microenvironments based on 4 types of cell...

  20. [The diagnostic value of microsatellite LOH analysis and the prognostic relevance of angiogenic gene expression in urinary bladder cancer].

    Science.gov (United States)

    Szarvas, Tibor

    2009-12-01

    Bladder cancer is the second most common malignancy affecting the urinary system. Currently, histology is the only tool that determines therapy and patients' prognosis. As the treatment of non-invasive (Ta/T1) and muscle invasive (T2-T4) bladder tumors are completely different, correct staging is important, although it is often hampered by disturbing factors. Molecular methods offer new prospects for early disease detection, confirmation of unclear histological findings and prognostication. Applying molecular biological methods, the present study is searching for answers to current diagnostic and prognostic problems in bladder carcinoma. We analyzed tumor, blood and/or urine samples of 334 bladder cancer patients and 117 control individuals. Genetic alterations were analyzed in urine samples of patients and controls, both by PCR-based microsatellite loss of heterozigosity (LOH) analysis using 12 fluorescently labeled primers and by DNA hybridization based UroVysion FISH technique using 4 probes, to assess the diagnostic values of these methods. Whole genome microsatellite analysis (with 400 markers) was performed in tumor and blood specimens of bladder cancer patients to find chromosomal regions, the loss of which may be associated with tumor stage. Furthermore, we assessed the prognostic value of Tie2, VEGF, Angiopoietin-1 and -2. We concluded that DNA analysis of voided urine samples by microsatellite analysis and FISH are sensitive and non-invasive methods to detect bladder cancer. Furthermore, we established a panel of microsatellite markers that could differentiate between non-invasive and invasive bladder cancer. However, further analyses in a larger cohort of patients are needed to assess their specificity and sensitivity. Finally, we identified high Ang-2 and low Tie2 gene expression as significant and independent risk factors of tumor recurrence and cancer related survival.

  1. HSD3B and gene-gene interactions in a pathway-based analysis of genetic susceptibility to bladder cancer.

    Directory of Open Access Journals (Sweden)

    Angeline S Andrew

    Full Text Available Bladder cancer is the 4(th most common cancer among men in the U.S. We analyzed variant genotypes hypothesized to modify major biological processes involved in bladder carcinogenesis, including hormone regulation, apoptosis, DNA repair, immune surveillance, metabolism, proliferation, and telomere maintenance. Logistic regression was used to assess the relationship between genetic variation affecting these processes and susceptibility in 563 genotyped urothelial cell carcinoma cases and 863 controls enrolled in a case-control study of incident bladder cancer conducted in New Hampshire, U.S. We evaluated gene-gene interactions using Multifactor Dimensionality Reduction (MDR and Statistical Epistasis Network analysis. The 3'UTR flanking variant form of the hormone regulation gene HSD3B2 was associated with increased bladder cancer risk in the New Hampshire population (adjusted OR 1.85 95%CI 1.31-2.62. This finding was successfully replicated in the Texas Bladder Cancer Study with 957 controls, 497 cases (adjusted OR 3.66 95%CI 1.06-12.63. The effect of this prevalent SNP was stronger among males (OR 2.13 95%CI 1.40-3.25 than females (OR 1.56 95%CI 0.83-2.95, (SNP-gender interaction P = 0.048. We also identified a SNP-SNP interaction between T-cell activation related genes GATA3 and CD81 (interaction P = 0.0003. The fact that bladder cancer incidence is 3-4 times higher in males suggests the involvement of hormone levels. This biologic process-based analysis suggests candidate susceptibility markers and supports the theory that disrupted hormone regulation plays a role in bladder carcinogenesis.

  2. The association of genetic variants in telomere maintenance genes with bladder cancer risk%端粒维持基因多态性与膀胱癌易感性的关系

    Institute of Scientific and Technical Information of China (English)

    顾成元; 朱耀; 叶定伟

    2013-01-01

    Telomere maintenance genes play an important role in maintaining the integrity of the telomere structure that protects chromosome ends, and telomere dysfunction may lead to tumorigenesis. Genetic variation in telomere maintenance genes has been confirmed. Cumulative evidence shows that the difference of telomere length and stability among the individual depends on the genetic variants of telomere maintenance genes. Genetic variants in telomere maintenance genes may affect telomere length and stability, thus the increased cancer risk. This review intends to summarize the association of genetic variants in telomere maintenance genes with bladder cancer risk.%  端粒维持基因在保持端粒稳定、维护染色体完整方面起重要作用,端粒功能紊乱将会导致肿瘤发生。在维持端粒稳定的基因中,已经发现多种基因存在单核苷酸多态性。随着研究的深入,越来越多的证据表明,个体间端粒稳定性及长度的差异主要取决于端粒维持基因的多态性。端粒维持基因单核苷酸多态性可能是导致端粒长度及稳定性存在个体差异及增加肿瘤易感性的主要因素之一。本文就端粒维持基因多态性与膀胱癌易感性关系的研究进展作一综述。

  3. Analysis of ochratoxin A blood levels in bladder cancer cases and healthy persons from Pakistan.

    Science.gov (United States)

    Aslam, Muhammad; Rivzi, S Abidul Hassan; Beg, Anwer Ejaz; Blaszkewicz, Meinolf; Golka, Klaus; Degen, Gisela H

    2012-01-01

    The mycotoxin ochratoxin A (OTA), a well-known human nephrotoxic and carcinogenic agent, is a public health concern in many countries. Exposure is assessed by means of mycotoxin analysis in food commodities and by human biomonitoring of OTA in blood samples. Data available from several European countries and some studies in Africa, Asia, and the Americas indicate frequent detection of OTA. Thus far, data from developing countries that compare blood levels in healthy and diseased individuals are scarce. Thus, the aim of this investigation was to determine OTA levels in blood samples of bladder cancer patients (n = 96) and healthy controls (n = 31) from Pakistan. OTA in blood plasma was analyzed after extraction by high-performance liquid chromatography (HPLC) with fluorescence detection. Among samples of 87 cancer patients and 30 controls, 92% in total contained quantifiable amounts of OTA. In bladder cancer cases the median OTA concentration was 0.19 ng/ml (mean 0.296; range: 0.03 to 3.41 ng/ml), and in healthy controls the median OTA was 0.19 ng/ml (mean 0.3; range: 0.04 to 1.24 ng/ml). The OTA levels found in the Pakistanian cohorts were comparable to those reported previously for the general population in the European Union. In conclusion, OTA is not likely to play a major role in the etiology of bladder cancer in the Karachi cohort, at least as the sole risk factor.

  4. The hOGG1 Ser326Cys gene polymorphism and susceptibility for bladder cancer: a meta-analysis

    Science.gov (United States)

    Wenjuan, Cao; Jianzhong, Lu; Chong, Li; Yanjun, Gao; Keqing, Lu; Hanzhang, Wang; Zhiping, Wang

    2016-01-01

    ABSTRACT Objective: To assess the susceptibility of the hOGG1 genetic polymorphism for bladder cancer and evaluate the impact of smoking exposure. Materials and Methods: Articles included in PubMed, Medline and Springer databases were retrieved using the following key words: “human 8-oxoguanine DNA glycosylase”, “OGG”, “OGG1”, “hOGG1”, “genetic variation”, “polymorphism” , “bladder cancer”, and “bladder carcinoma” to Meta-analysis was performed to detect whether there were differences between the bladder cancer group and the control group about the distribution of genotypes of the hOGG1 gene. Results: The results showed that there are no significant associations between the hOGG1 326Cys polymorphism and bladder cancer: GG vs. CC (OR: 1.09, 95% CI: 0.85–1.40, p=0.480); GC vs. CC (OR: 1.05, 95% CI: 0.85–1.28, p=0.662); GG+GC vs. CC (OR: 1.04, 95% CI: 0.89–1.21, p=0.619); GG vs. GC+CC(OR: 1.02, 95% CI: 0.78–1.33, p=0.888); G vs. C (OR: 1.01, 95% CI: 0.91–1.13, p=0.818). In the smoker population, no significant associations between the hOGG1 326Cys polymorphism and bladder cancer were observed for all the models. However, individuals carrying the hOGG1 Cys326Cys genotype have increased risk for bladder cancer compared to those carrying the hOGG1 Ser326Ser genotype in the non-smoker Asian population. Conclusion: The hOGG1 326Cys polymorphisms aren't a risk factor for bladder cancer, especially in the smoker population. But GG genotype is a risk factor for bladder cancer to the non-smoker Asian population compared with CC genotype. PMID:27583352

  5. A case-control study of bladder cancer in the United States rubber and tyre industry.

    Science.gov (United States)

    Checkoway, H; Smith, A H; McMichael, A J; Jones, F S; Monson, R R; Tyroler, H A

    1981-01-01

    A case-control study of bladder cancer was conducted in five United States rubber and tyre companies to determine if there were high-risk jobs and work areas within the industry. The study included 220 male cases of bladder cancer, of whom 107 were identified from hospital record reviews and 113 from death certificates. Each case was matched individually with two industry controls by sex, race, year of birth, and company. One control was matched additionally by year of hire and duration of employment. Comparisons of cases and controls not matched by year of hire and age of hire showed no differences for those variables, which suggests that age and calendar period of first exposure to the industry were not risk determinants. When the work histories of both cases and controls were contrasted it was found that cases were more likely than controls to have worked in milling (odds ratio (OR) = 1.91) and calender operation (OR = 2.21) jobs. The relative risk estimates for milling and calender operation both exhibited linear trends of increase with duration of exposure. Milling and calender operation jobs entail potential exposures to volatilised reaction products from heated rubber stock. A better understanding of aetiological associations with job type will require more detailed characterisation of the work environment with regard to the sources and levels of aromatic amines and other suspected bladder carcinogens. PMID:7272236

  6. Marker evaluation of human breast and bladder cancers

    Energy Technology Data Exchange (ETDEWEB)

    Mayall, B.H.; Carroll, P.R.; Chen, Ling-Chun; Cohen, M.B.; Goodson, W.H. III; Smith, H.S.; Waldman, F.M. (California Univ., San Francisco, CA (USA))

    1990-11-02

    We are investigating multiple markers in human breast and bladder cancers. Our aim is to identify markers that are clinically relevant and that contribute to our understanding of the disease process in individual patients. Good markers accurately assess the malignant potential of a cancer in an individual patient. Thus, they help identify those cancers that will recur, and they may be used to predict more accurately time to recurrence, response to treatment, and overall prognosis. Therapy and patient management may then be optimized to the individual patient. Relevant markers reflect the underlying pathobiology of individual tumors. As a tissue undergoes transformation from benign to malignant, the cells lose their differentiated phenotype. As a generalization, the more the cellular phenotype, cellular proliferation and cellular genotype depart from normal, the more advanced is the tumor in its biological evolution and the more likely it is that the patient has a poor prognosis. We use three studies to illustrate our investigation of potential tumor markers. Breast cancers are labeled in vivo with 5-bromodeoxyuridine (BrdUrd) to give a direct measure of the tumor labeling index. Bladder cancers are analyzed immunocytochemically using an antibody against proliferation. Finally, the techniques of molecular genetics are used to detect allelic loss in breast cancers. 6 refs., 3 figs.

  7. Possible link of pioglitazone with bladder cancer in Japanese patients with type 2 diabetes.

    Science.gov (United States)

    Fujimoto, Kanta; Hamamoto, Yoshiyuki; Honjo, Sachiko; Kawasaki, Yukiko; Mori, Kanako; Tatsuoka, Hisato; Matsuoka, Atsuko; Wada, Yoshiharu; Ikeda, Hiroki; Fujikawa, Jun; Koshiyama, Hiroyuki

    2013-02-01

    We retrospectively examined the frequency of bladder cancer in Japanese patients with type 2 diabetes in relation to use of pioglitazone. Among a total of 663 patients identified to be taking pioglitazone, 9 had bladder cancer (1.36%). Overall the hazard ratio of 1.75 [95% CI: 0.89-3.45] for pioglitazone for bladder cancer was not significant. However the prevalence of bladder cancer was 2.10% in patients taking pioglitazone for less than 24 months which was significant increased (HR 2.73 [95% CI: 1.11-6.72]).

  8. Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer

    NARCIS (Netherlands)

    Rafnar, T.; Sulem, P.; Thorleifsson, G.; Vermeulen, S.; Helgason, H.; Saemundsdottir, J.; Gudjonsson, S.A.; Sigurdsson, A.; Stacey, S.N.; Gudmundsson, J.; Johannsdottir, H.; Alexiusdottir, K.; Petursdottir, V.; Nikulasson, S.; Geirsson, G.; Jonsson, T.; Aben, K.K.H.; Grotenhuis, A.J.; Verhaegh, G.W.C.T.; Dudek, A.M.D.; Witjes, J.A.; Heijden, A.G. van der; Vrieling, A.; Galesloot, T.E.; Juan, A. de; Panadero, A.; Rivera, F.; Hurst, C.; Bishop, D.T.; Sak, S.C.; Choudhury, A.; Teo, M.T.; Arici, C.; Carta, A.; Toninelli, E.; Verdier, P. de; Rudnai, P.; Gurzau, E; Koppova, K.; Keur, K.A. van der; Lurkin, I.; Goossens, M.; Kellen, E.; Guarrera, S.; Russo, A.; Critelli, R.; Sacerdote, C.; Vineis, P.; Krucker, C.; Zeegers, M.P.; Gerullis, H.; Ovsiannikov, D.; Volkert, F.; Hengstler, J.G.; Selinski, S.; Magnusson, O.T.; Masson, G.; Kong, A.; Gudbjartsson, D.; Lindblom, A.; Zwarthoff, E.; Porru, S.; Golka, K.; Buntinx, F.; Matullo, G.; Kumar, R.; Mayordomo, J.I.; Steineck, D.G.; Kiltie, A.E.; Jonsson, E.; Radvanyi, F.; Knowles, M.A.; Thorsteinsdottir, U.; Kiemeney, B.; Stefansson, K.

    2014-01-01

    Genome-wide association studies (GWAS) of urinary bladder cancer (UBC) have yielded common variants at 12 loci that associate with risk of the disease. We report here the results of a GWAS of UBC including 1670 UBC cases and 90 180 controls, followed by replication analysis in additional 5266 UBC ca

  9. CONSTRUCTION AND EXPRESSION OF A HUMAN-MOUSE CHIMERIC ANTIBODY AGAINST HUMAN BLADDER CANCER

    Institute of Scientific and Technical Information of China (English)

    白银; 王琰; 周丽君; 俞莉章

    2001-01-01

    To construct and express a human-mouse chimeric antibody against human bladder cancer. Method: The variable region genes of anti-human bladder cancer monoclonal antibody BDI-1 were cloned by RT-PCR. A human-mouse chimeric antibody expression vector was constructed and transfected into CHO cells. The chimeric antibody against bladder cancer was expressed and characterized. Result: Eukaryotic expression vector of the chimeric antibody against human bladder carcinoma was successfully constructed, and was expressed in eukaryotic cells; the expressed chimeric antibody ch-BDI showed same specificity as its parent McAb against human bladder cancer cells. Conclusion: The constructed chimeric antibody was expressed successfully in eukaryotic cells, and the chimeric antibody had desired affinity against human bladder cancer cells.

  10. Self-assembled tumor-targeting hyaluronic acid nanoparticles for photothermal ablation in orthotopic bladder cancer.

    Science.gov (United States)

    Lin, Tingsheng; Yuan, Ahu; Zhao, Xiaozhi; Lian, Huibo; Zhuang, Junlong; Chen, Wei; Zhang, Qing; Liu, Guangxiang; Zhang, Shiwei; Chen, Wei; Cao, Wenmin; Zhang, Chengwei; Wu, Jinhui; Hu, Yiqiao; Guo, Hongqian

    2017-02-15

    Bladder cancer is one of the most frequent malignancies in the urinary system. Radical cystectomy is inevitable when bladder cancer progresses to a muscle-invasive disease. However, cystectomy still causes a high risk of death and a low quality of life (such as ureter-abdomen ostomy, uroclepsia for ileal-colon neobladder). Therefore, more effective treatments as well as bladder preservation are needed. We developed self-assembled tumor-targeting hyaluronic acid-IR-780 nanoparticles for photothermal ablation in over-expressing CD44 (the receptor for HA) bladder cancer, which show high tumor selectivity, high treatment efficacy, good bioavailability, and excellent biocompatibility. The nanoparticles demonstrated a stable spherical nanostructure in aqueous conditions with good mono-dispersity, and their average size was 171.3±9.14nm. The nanoparticles can be degraded by hyaluronidase when it is over-expressed in bladder cells; therefore, they appear to have a hyaluronidase-responsive "OFF/ON" behavior of a fluorescence signal. HA-IR-780 NPs also showed high photothermal efficiency; 2.5, 5, 10 and 20μg/mL of NPs had a maximum temperature increase of 11.2±0.66°C, 18.6±0.75°C, 26.8±1.11°C and 32.3±1.42°C. The in vitro cell viability showed that MB-49 cells could be efficiently ablated by combining HA-IR-780 NPs with 808nm laser irradiation. Then, in vivo biodistribution showed the HA-IR-780 NPs are targeted for accumulation in bladder cancer cells but have negligible accumulation in normal bladder wall. The photothermal therapeutic efficacy of HA-IR-780 NPs in the orthotopic bladder cancer model showed tumors treated with NPs had a maximum temperature of 48.1±1.81°C after 6min of laser irradiation. The tumor volume was approximately 65-75mm(3) prior to treatment. After 12days, the tumor sizes for the PBS, PBS plus laser irradiation and HA-IR-780 NPs-treated groups were 784.75mm(3), 707.5mm(3), and 711.37mm(3), respectively. None of the tumors in the HA-IR-780

  11. Bladder Cancer and Arsenic Exposure: Differences in the Two Populations Enrolled in A Study in Southwest Taiwan

    Institute of Scientific and Technical Information of China (English)

    STEVEN H. LAMM; DANIEL M. BYRD; MICHAEL B. KRUSE; MANNING FEINLEIB; SHENG-HAN LAI

    2003-01-01

    Objective Analyses of bladder cancer mortality in the Black Foot Disease (BFD) endemic area of southwest Taiwan conducted by Morales et al. showed a discontinuity in risk at 400 μg/L arsenic in the drinking water in a stratified analysis and no discontinuity in a continuous analysis. As the continuous analysis presentation had been used by both the NRC and the EPA to assess the carcinogenic risk from arsenic ingestion, an explanation of the discontinuity was sought. Methods Review of 40 years of published health studies of the BFD-endemic area of SW Taiwan showed that earlier publications had limited their cancer associations with arsenic levels in artesian well waters and that the reports of Morales et al., NRC, and EPA failed to do so. Underlying data for the Morales et al.study were obtained from the appendix to the NRC report. Bladder cancer mortality rates werecalculated from case counts and person-years of observation for each study village. Villages werecategorized by water source according to the descriptions from the underlying study. Graphic and regression analyses were conducted of the bladder cancer mortality rates using exposure as a continuous variable and simultaneously stratifying by water source. Results The median village well arsenic levels ranged from 350 to 934 μg/L for villages solely dependent on artesian well water and from 10 to 717 μg/L for villages not solely dependent on artesian well water. Bladder cancer mortality rates were found to be dependent upon the arsenic level only for those villages that were solely dependent on artesian well water for their water source. Bladder cancer mortality rates were found to be independent of arsenic level for villages with non-artesian well water sources. Conclusions The data indicate that arsenic exposure levels do not explain the bladder cancer mortality risk in SW Taiwan among villages not dependent upon artesian well water. The association for villages dependent upon artesian well water may be

  12. Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile

    Energy Technology Data Exchange (ETDEWEB)

    Melak, Dawit [Global Health Sciences, University of California, San Francisco, San Francisco, CA (United States); Ferreccio, Catterina [Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago (Chile); Kalman, David [School of Public Health and Community Medicine, University of Washington, Seattle, WA (United States); Parra, Roxana [Hospital Regional de Antofagasta, Antofagasta (Chile); Acevedo, Johanna; Pérez, Liliana; Cortés, Sandra [Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago (Chile); Smith, Allan H.; Yuan, Yan; Liaw, Jane [Arsenic Health Effects Research Group, School of Public Health, University of California, Berkeley, Berkeley, CA (United States); Steinmaus, Craig, E-mail: craigs@berkeley.edu [Arsenic Health Effects Research Group, School of Public Health, University of California, Berkeley, Berkeley, CA (United States); Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, CA (United States)

    2014-01-15

    In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although this process is not complete in most people. The trivalent form of MMA is highly toxic in vitro and previous studies have identified associations between the proportion of urinary arsenic as MMA (%MMA) and several arsenic-related diseases. To date, however, relatively little is known about its role in lung cancer, the most common cause of arsenic-related death, or about its impacts on people drinking water with lower arsenic concentrations (e.g., < 200 μg/L). In this study, urinary arsenic metabolites were measured in 94 lung and 117 bladder cancer cases and 347 population-based controls from areas in northern Chile with a wide range of drinking water arsenic concentrations. Lung cancer odds ratios adjusted for age, sex, and smoking by increasing tertiles of %MMA were 1.00, 1.91 (95% confidence interval (CI), 0.99–3.67), and 3.26 (1.76–6.04) (p-trend < 0.001). Corresponding odds ratios for bladder cancer were 1.00, 1.81 (1.06–3.11), and 2.02 (1.15–3.54) (p-trend < 0.001). In analyses confined to subjects only with arsenic water concentrations < 200 μg/L (median = 60 μg/L), lung and bladder cancer odds ratios for subjects in the upper tertile of %MMA compared to subjects in the lower two tertiles were 2.48 (1.08–5.68) and 2.37 (1.01–5.57), respectively. Overall, these findings provide evidence that inter-individual differences in arsenic metabolism may be an important risk factor for arsenic-related lung cancer, and may play a role in cancer risks among people exposed to relatively low arsenic water concentrations. - Highlights: • Urine arsenic metabolites were measured in cancer cases and controls from Chile. • Higher urine %MMA values were associated with increased lung and bladder cancer. • %MMA-cancer associations were seen at drinking water arsenic levels < 200 μg/L.

  13. Expression of Bmi-1 is a prognostic marker in bladder cancer

    Directory of Open Access Journals (Sweden)

    Xu Li-Hua

    2009-02-01

    Full Text Available Abstract Background The molecular mechanisms of the development and progression of bladder cancer are poorly understood. The objective of this study was to analyze the expression of Bmi-1 protein and its clinical significance in human bladder cancer. Methods We examined the expression of Bmi-1 mRNA and Bmi-1 protein by RT-PCR and Western blot, respectively in 14 paired bladder cancers and the adjacent normal tissues. The expression of Bmi-1 protein in 137 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between expression of Bmi-1, and clinicopathologic features and prognosis. Results Expression of Bmi-1 mRNA and protein was higher in bladder cancers than in the adjacent normal tissues in 14 paired samples (P P P P P > 0.5. In superficial bladder cancers, the expression of Bmi-1 protein in recurrent cases was higher than in recurrence-free cases (62.5% versus 13.7%, P P P > 0.05. Five-year survival in the group with higher Bmi-1 expression was 50.8%, while it was 78.5% in the group with lower Bmi-1 expression (P P Conclusion Expression of Bmi-1 was greater in bladder cancers than in the adjacent normal tissues. The examination of Bmi-1 protein expression is potentially valuable in prognostic evaluation of bladder cancer.

  14. Treatment Options by Stage (Bladder Cancer)

    Science.gov (United States)

    ... from a well that has high levels of arsenic . Drinking water that has been treated with chlorine . ... of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative ...

  15. Screening for Bladder and Other Urothelial Cancers

    Science.gov (United States)

    ... from a well that has high levels of arsenic . Drinking water that has been treated with chlorine . ... trials also are meant to show whether early detection (finding cancer before it causes symptoms ) decreases a ...

  16. Management of Bladder Cancer following Solid Organ Transplantation

    Directory of Open Access Journals (Sweden)

    Jeffrey J. Tomaszewski

    2011-01-01

    Full Text Available Objective. Present our experience managing bladder cancer following liver and renal transplantation. Methods. Single institution retrospective review of patients diagnosed with bladder urothelial carcinoma (BUC following solid organ transplantation between January 1992 and December 2007. Results. Of the 2,925 renal and 2,761 liver transplant recipients reviewed, we identified eleven patients (0.2% following transplant diagnosed with BUC. Two patients with low grade T1 TCC were managed by TURBT. Three patients with CIS and one patient with T1 low grade BUC were treated by TURBT and adjuvant BCG. All four are alive and free of recurrence at a mean follow-up of 51 ± 22 months. One patient with T1 high grade BUC underwent radical cystectomy and remains disease free with a follow-up of 98 months. Muscle invasive TCC was diagnosed in four patients at a median of 3.6 years following transplantation. Two patients are recurrence free at 24 and 36 months following radical cystectomy. Urinary diversion and palliative XRT were performed in one patient with un-resectable disease. Conclusions. Bladder cancer is uncommon following renal and liver transplantation, but it can be managed successfully with local and/or extirpative therapy. The use of intravesical BCG is possible in select immunosuppressed patients.

  17. Bladder cancer diagnosis from bladder wash by Fourier transform infrared spectroscopy as a novel test for tumor recurrence.

    Science.gov (United States)

    Gok, Seher; Aydin, Ozge Z; Sural, Yavuz S; Zorlu, Ferruh; Bayol, Umit; Severcan, Feride

    2016-09-01

    This study proposes Fourier Transform Infrared (FTIR) spectroscopy as a more sensitive, rapid, non-destructive and operator-independent analytical diagnostic method for bladder cancer recurrence from bladder wash than other routinely used urine cytology and cystoscopy methods. A total of 136 patients were recruited. FTIR spectroscopic experiments were carried out as a blind study, the classification results of which were then compared with those of cytology and cystoscopy. Firstly, 71 samples (n = 37; bladder cancer and n = 34; control) were studied with transmittance FTIR spectroscopy. After achieving successful differentiation of the groups, to develop a more rapid diagnostic tool and check the reproducibility of the results, the work was continued with different samples (n = 65 as n = 44; bladder cancer and n = 21; control), using the reflection mode (ATR) of FTIR spectroscopy by a different operator. The results revealed significant alterations in moleculer content in the cancer group. Based on the spectral differences, using transmittance FTIR spectroscopy coupled with chemometrics, the diseased group was successfully differentiated from the control. When only carcinoma group was taken into consideration a sensitivity value of 100% was achieved. Similar results were also obtained by ATR-FTIR spectroscopy. This study shows the power of infrared spectroscopy in the diagnosis of bladder cancer.

  18. Amygdalin influences bladder cancer cell adhesion and invasion in vitro.

    Directory of Open Access Journals (Sweden)

    Jasmina Makarević

    Full Text Available The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as well as tumor cell migration was examined. Effects of drug treatment on integrin α and β subtypes, on integrin-linked kinase (ILK and total and activated focal adhesion kinase (FAK were also determined. Integrin knock-down was carried out to evaluate integrin influence on migration and adhesion. A 24 h or 2 week amygdalin application distinctly reduced tumor cell adhesion and migration of UMUC-3 and RT112 cells. TCCSUP adhesion was also reduced, but migration was elevated under amygdalin. Integrin subtype expression was significantly and specifically altered by amygdalin depending on the cell line. ILK was moderately, and activated FAK strongly, lost in all tumor cell lines in the presence of amygdalin. Knock down of β1 integrin caused a significant decrease in both adhesion and migration of UMUC-3 cells, but a significant increase in TCCSUP adhesion. Knock down of β4 integrin caused a significant decrease in migration of RT112 cells. Since the different actions of amygdalin on the different cell lines was mirrored by β1 or β4 knock down, it is postulated that amygdalin influences adhesion and migratory properties of bladder cancer cells by modulating β1 or β4 integrin expression. The amygdalin induced increase in TCCSUP migratory behavior indicates that any anti-tumor benefits from amygdalin (seen with the other two cell lines may depend upon the cancer cell type.

  19. Amygdalin influences bladder cancer cell adhesion and invasion in vitro.

    Science.gov (United States)

    Makarević, Jasmina; Rutz, Jochen; Juengel, Eva; Kaulfuss, Silke; Tsaur, Igor; Nelson, Karen; Pfitzenmaier, Jesco; Haferkamp, Axel; Blaheta, Roman A

    2014-01-01

    The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml) was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as well as tumor cell migration was examined. Effects of drug treatment on integrin α and β subtypes, on integrin-linked kinase (ILK) and total and activated focal adhesion kinase (FAK) were also determined. Integrin knock-down was carried out to evaluate integrin influence on migration and adhesion. A 24 h or 2 week amygdalin application distinctly reduced tumor cell adhesion and migration of UMUC-3 and RT112 cells. TCCSUP adhesion was also reduced, but migration was elevated under amygdalin. Integrin subtype expression was significantly and specifically altered by amygdalin depending on the cell line. ILK was moderately, and activated FAK strongly, lost in all tumor cell lines in the presence of amygdalin. Knock down of β1 integrin caused a significant decrease in both adhesion and migration of UMUC-3 cells, but a significant increase in TCCSUP adhesion. Knock down of β4 integrin caused a significant decrease in migration of RT112 cells. Since the different actions of amygdalin on the different cell lines was mirrored by β1 or β4 knock down, it is postulated that amygdalin influences adhesion and migratory properties of bladder cancer cells by modulating β1 or β4 integrin expression. The amygdalin induced increase in TCCSUP migratory behavior indicates that any anti-tumor benefits from amygdalin (seen with the other two cell lines) may depend upon the cancer cell type.

  20. Photodynamic therapy: applications in bladder cancer and other malignancies.

    Science.gov (United States)

    Chang, S C; Bown, S G

    1997-11-01

    Photodynamic therapy (PDT) has gained popularity in the past 10 years because of advances in laser and pharmacokinetic technologies and the development of new photosensitizers. Early studies on PDT with focal illumination for papillary bladder cancer obtained reasonable response rates for small tumors but recurrence was common. Whole bladder irradiation, once a suitable light-delivery system had been developed, gave promising outcomes with acceptable rates of complications. PDT for prostate cancer is still at the experimental stage but initial results have been promising. Clinical trials of PDT for brain tumors have shown no significant complications but no improvement in survival rate compared with other treatment modalities. PDT is particularly useful for early superficial lung cancers that are localized to one or a few discrete sites; it is also safe to use in patients who are too sick to be treated with conventional therapies. Preoperative PDT has reduced the extent of surgery necessary in some patients. Clinical experience with PDT for gynecological cancer is limited and prospective studies are needed. In head and neck oncology, PDT should prove a useful option, but methodological problems need to be overcome. Good responses of esophageal cancer to PDT have led to governmental approval of Photofrin, a photosensitizer, in several countries for either palliative use or treatment of inoperable or recurrent cancer. The use of PDT for early gastric cancer has great potential but several technical problems remain. PDT has proven generally effective for skin cancer when hematoporphyrin derivative or Photofrin is used but more long-term follow-up data are required for PDT with 5-aminolevulinic acid. Overall, PDT is changing from a scientific curiousity into an accepted modality for the treatment of cancer, with an improved likelihood of finding further clinical applications.

  1. Photodynamic therapy in the prophylactic management of bladder cancer

    Science.gov (United States)

    Nseyo, Unyime O.; Lundahl, Scott L.; Merrill, Daniel C.

    1991-06-01

    Nine patients were treated with red light whole bladder photodynamic therapy (WBPDT): five had mucosal involvement (Ta) and four submucosal invasion (T1). Patients received slow intravenous injection with 2mg/kg body weight of photofrin 48-72 hours before undergoing global light treatment via a 22-French cystoscope with a 400-micron quartz fiber bulb (isotropic) tip fiber. Three months after PDT, eight of the patients had normal cystoscopy, and negative biopsy and urine cytology. Two patients who had recurrences at six and twelve months were retreated with a higher dose (20 J/cm2). They had no increased morbidity and no evidence of recurrent disease six months later. WBPDT should be considered as an important alternative treatment for patients who have recurrent or refractory superficial bladder cancer.

  2. A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci

    Science.gov (United States)

    Rothman, Nathaniel; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Malats, Nuria; Wu, Xifeng; Figueroa, Jonine; Real, Francisco X; Van Den Berg, David; Matullo, Giuseppe; Baris, Dalsu; Thun, Michael; Kiemeney, Lambertus A; Vineis, Paolo; De Vivo, Immaculata; Albanes, Demetrius; Purdue, Mark P; Rafnar, Thorunn; Hildebrandt, Michelle A T; Kiltie, Anne E; Cussenot, Olivier; Golka, Klaus; Kumar, Rajiv; Taylor, Jack A; Mayordomo, Jose I; Jacobs, Kevin B; Kogevinas, Manolis; Hutchinson, Amy; Wang, Zhaoming; Fu, Yi-Ping; Prokunina-Olsson, Ludmila; Burdette, Laurie; Yeager, Meredith; Wheeler, William; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Johnson, Alison; Schwenn, Molly; Karagas, Margaret R; Schned, Alan; Andriole, Gerald; Grubb, Robert; Black, Amanda; Jacobs, Eric J; Diver, W Ryan; Gapstur, Susan M; Weinstein, Stephanie J; Virtamo, Jarmo; Cortessis, Victoria K; Gago-Dominguez, Manuela; Pike, Malcolm C; Stern, Mariana C; Yuan, Jian-Min; Hunter, David; McGrath, Monica; Dinney, Colin P; Czerniak, Bogdan; Chen, Meng; Yang, Hushan; Vermeulen, Sita H; Aben, Katja K; Witjes, J Alfred; Makkinje, Remco R; Sulem, Patrick; Besenbacher, Soren; Stefansson, Kari; Riboli, Elio; Brennan, Paul; Panico, Salvatore; Navarro, Carmen; Allen, Naomi E; Bueno-de-Mesquita, H Bas; Trichopoulos, Dimitrios; Caporaso, Neil; Landi, Maria Teresa; Canzian, Federico; Ljungberg, Borje; Tjonneland, Anne; Clavel-Chapelon, Francoise; Bishop, David T; Teo, Mark T W; Knowles, Margaret A; Guarrera, Simonetta; Polidoro, Silvia; Ricceri, Fulvio; Sacerdote, Carlotta; Allione, Alessandra; Cancel-Tassin, Geraldine; Selinski, Silvia; Hengstler, Jan G; Dietrich, Holger; Fletcher, Tony; Rudnai, Peter; Gurzau, Eugen; Koppova, Kvetoslava; Bolick, Sophia C E; Godfrey, Ashley; Xu, Zongli; Sanz-Velez, José I; García-Prats, María D; Sanchez, Manuel; Valdivia, Gabriel; Porru, Stefano; Benhamou, Simone; Hoover, Robert N; Fraumeni, Joseph F; Silverman, Debra T; Chanock, Stephen J

    2010-01-01

    We conducted a multi-stage, genome-wide association study (GWAS) of bladder cancer with a primary scan of 589,299 single nucleotide polymorphisms (SNPs) in 3,532 cases and 5,120 controls of European descent (5 studies) followed by a replication strategy, which included 8,381 cases and 48,275 controls (16 studies). In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1; rs1014971, (P=8×10−12) maps to a non-genic region of chromosome 22q13.1; rs8102137 (P=2×10−11) on 19q12 maps to CCNE1; and rs11892031 (P=1×10−7) maps to the UGT1A cluster on 2q37.1. We confirmed four previous GWAS associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P=4×10−11) and a tag SNP for NAT2 acetylation status (P=4×10−11), as well as demonstrated smoking interactions with both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into mechanisms of carcinogenesis. PMID:20972438

  3. Physical and clinical implications of radiotherapy treatment of prostate cancer using a full bladder protocol

    Energy Technology Data Exchange (ETDEWEB)

    Cambria, Raffaella; Cattani, Federica; Luraschi, Rosa; Pedroli, Guido [Istituto Europeo di Oncologia, Milan (Italy). Dept. of Medical Physics; Jereczek-Fossa, Barbara A.; Orecchia, Roberto [Istituto Europeo di Oncologia, Milan (Italy). Dept. of Radiation Oncology; Univ. degli Studi of Milano, Milan (Italy); Zerini, Dario [Istituto Europeo di Oncologia, Milan (Italy). Dept. of Radiation Oncology; Serafini, Flavia [Unita operativa di radioterapia, Azienda Ospedaliera Sant' Anna, Como (Italy)

    2011-12-15

    To assess the dosimetric and clinical implication when applying the full bladder protocol for the treatment of the localized prostate cancer (PCA). A total of 26 consecutive patients were selected for the present study. Patients underwent two series of CT scans: the day of the simulation and after 40 Gy. Each series consisted of two consecutive scans: (1) full bladder (FB) and (2) empty bladder (EB). The contouring of clinical target volumes (CTVs) and organs at risk (OAR) were compared to evaluate organ motion. Treatment plans were compared by dose distribution and dose-volume histograms (DVH). CTV shifts were negligible in the laterolateral and superior-inferior directions (the maximum shift was 1.85 mm). Larger shifts were recorded in the anterior-posterior direction (95% CI, 0.83-4.41 mm). From the dosimetric point of view, shifts are negligible: the minimum dose to the CTV was 98.5% (median; 95%CI, 95-99%). The potential advantage for GU toxicity in applying the FB treatment protocol was measured: the ratio between full and empty bladder dose-volume points (selected from our protocol) is below 0.61, excluding the higher dose region where DVHs converge. Having a FB during radiotherapy does not affect treatment effectiveness, on the contrary it helps achieve a more favorable DVH and lower GU toxicities.

  4. The feasibility of computational modelling technique to detect the bladder cancer.

    Science.gov (United States)

    Keshtkar, Ahmad; Mesbahi, Asghar; Rasta, S H; Keshtkar, Asghar

    2010-01-01

    A numerical technique, finite element analysis (FEA) was used to model the electrical properties, the bio impedance of the bladder tissue in order to predict the bladder cancer. This model results showed that the normal bladder tissue have significantly higher impedance than the malignant tissue that was in opposite with the impedance measurements or the experimental results. Therefore, this difference can be explained using the effects of inflammation, oedema on the urothelium and the property of the bladder as a distensible organ. Furthermore, the different current distributions inside the bladder tissue (in histological layers) in normal and malignant cases and finally different applied pressures over the bladder tissue can cause different impedances for the bladder tissue. Finally, it is believed that further studies have to be carried out to characterise the human bladder tissue using the electrical impedance measurement and modelling techniques.

  5. Case-control study of bladder cancer and drinking water arsenic in the western United States.

    Science.gov (United States)

    Steinmaus, Craig; Yuan, Yan; Bates, Michael N; Smith, Allan H

    2003-12-15

    Numerous epidemiologic investigations have identified links between high concentrations of arsenic in drinking water and cancer, although the risks at lower exposures are largely unknown. This paper presents the results of a case-control study of arsenic ingestion and bladder cancer in seven counties in the western United States. These counties contain the largest populations historically exposed to drinking water arsenic at concentrations near 100 microg/liter. All incident cases diagnosed from 1994 to 2000 were recruited. Individual data on water sources, water consumption patterns, smoking, and other factors were collected for 181 cases and 328 controls. Overall, no increased risks were identified for arsenic intakes greater than 80 microg/day (odds ratio=0.94, 95% confidence interval: 0.56, 1.57; linear trend, p=0.48). These risks are below predictions based on high dose studies from Taiwan. When the analysis was focused on exposures 40 or more years ago, an odds ratio of 3.67 (95% confidence interval: 1.43, 9.42; linear trend, p<0.01) was identified for intakes greater than 80 microg/day (median intake, 177 microg/day) in smokers. These data provide some evidence that smokers who ingest arsenic at concentrations near 200 microg/day may be at increased risk of bladder cancer.

  6. Bladder Cancer Screening in Lebanese Population: There is Nothing more Unequal than the Equal Treatment of Unequal People.

    Science.gov (United States)

    Shahait, Mohammed; Bulbul, Muhammad

    2016-10-27

    Bladder cancer screening has been perplexing the uro-oncological community for the last decade. In this commentary, we ruminate on the feasibility of bladder cancer screening in our population based on epidemiological proponents.

  7. Efficacy of transurethral resection of bladder tumor in treatment of elderly muscle-invasive bladder cancer

    Institute of Scientific and Technical Information of China (English)

    Yu Zhou; Min He; Hong-Tao Jia; Yun-Fei Li; Mao-Hua Luo

    2016-01-01

    Objective:To study the clinical efficacy of transurethral resection of bladder tumor (TURBT) in the treatment of elderly muscle-invasive bladder cancer (MIBC), and observe the changes of serum IGF-1, VEGF, BLCA-4, and IL-8 levels before and after treatment.Methods: A total of 56 elderly patients with MIBC who were admitted in our hospital were included in the study and divided into the treatment group (n=30) and the control group (n=26). The patients in the control group were given radical cystectomy, while the patients in the treatment group were given TURBT and bladder irrigation chemotherapy after operation. The surgical complications and survival in the two groups were observed. The serum IGF-1 and VEGF levels, and urine BLCA-4 and IL-8 levels before and after treatment in the two groups were detected.Results:The difference of serum IGF-1 and VEGF levels before operation between the two groups was not statistically significant (P>0.05). The serum IGF-1 and VEGF levels 7 d after operation were significantly reduced when compared with before operation (P<0.01), and the difference between the two groups was statistically significant (P<0.05 orP<0.01). The tumor-free survival rate 2 and 3 years after operation in the observation group were significantly higher than those in the control group (P<0.05).Conclusions: TURBT in the treatment of elderly MIBC has a preferable clinical effect, and can shorten the operation time, with a small trauma and less side effects.

  8. [The role of low-field strength magnetic resonance imaging in bladder cancer staging].

    Science.gov (United States)

    Lutsenko, P E; Bulanova, T V; Chernyshev, I V; Churaiants, V V

    2007-01-01

    This article shows the role of magnetic resonance imaging (MRI) in complex diagnostics of urinary bladder cancer. The paper analyzes the authors' own data of urinary bladder MRI in 40 patients with histologically proven bladder cancer. This study demonstrates the additional capacities of low-field strength MRI with enhanced technique including conventional T1-, T2-weighted images along with FLAIR and PD images.

  9. An unusual case of cancer of the urachal remnant following repair of bladder exstrophy.

    LENUS (Irish Health Repository)

    Fanning, D M

    2009-03-18

    INTRODUCTION: We report the first case of cancer of the urachal remnant following repair of bladder exstrophy, in a renal transplant recipient. METHOD: A retrospective review of this clinical case and the associated literature were performed. CONCLUSION: This unusual case highlights two very rare entities. Bladder exstrophy has an incidence of 1 in 50,000 newborns, whereas urachal cancer accounts for less than 1% of all bladder tumours.

  10. An unusual case of cancer of the urachal remnant following repair of bladder exstrophy.

    LENUS (Irish Health Repository)

    Fanning, D M

    2012-02-01

    INTRODUCTION: We report the first case of cancer of the urachal remnant following repair of bladder exstrophy, in a renal transplant recipient. METHOD: A retrospective review of this clinical case and the associated literature were performed. CONCLUSION: This unusual case highlights two very rare entities. Bladder exstrophy has an incidence of 1 in 50,000 newborns, whereas urachal cancer accounts for less than 1% of all bladder tumours.

  11. Low ANXA10 expression is associated with disease aggressiveness in bladder cancer

    DEFF Research Database (Denmark)

    Munksgaard, Pia; Mansilla, Francisco; Brems-Eskildsen, Anne Sofie;

    2011-01-01

    Markers for outcome prediction in bladder cancer are urgently needed. We have previously identified a molecular signature for predicting progression in non-muscle-invasive bladder cancer. ANXA10 was one of the markers included in the signature and we now validated the prognostic relevance of ANXA...

  12. IDENTIFICATION OF INTERSPECIES CONCORDANCE OF MECHANISMS OF ARSENIC INDUCED BLADDER CANCER BY GENE EXPRESSION.

    Science.gov (United States)

    Arsenic is a human carcinogen that induces urinary bladder cancer. Several mechanisms have been proposed for arsenic-induced cancer. Although inorganic arsenic (iAs) does not induce tumors in adult rodents, dimethylarsinic acid (DMA), a major metabolite of iAs, is a rat bladder c...

  13. Methylation Markers for Urine-Based Detection of Bladder Cancer: The Next Generation of Urinary Markers for Diagnosis and Surveillance of Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Thomas Reinert

    2012-01-01

    Full Text Available Cancer of the urinary bladder is the fifth most common neoplasm in the industrialized countries. Diagnosis and surveillance are dependent on invasive evaluation with cystoscopy and to some degree cytology as an adjunct analysis. Nomuscle invasive bladder cancer is characterized by frequent recurrences after resection, and up to 30% will develop an aggressive phenotype. The journey towards a noninvasive test for diagnosing bladder cancer, in order to replace or extend time between cystoscopy, has been ongoing for more than a decade. However, only a handful of tests that aid in clinical decision making are commercially available. Recent reports of DNA methylation in urine specimens highlight a possible clinical use of this marker type, as high sensitivities and specificities have been shown. This paper will focus on the currently available markers NMP22, ImmunoCyt, and UroVysion as well as novel DNA methylation markers for diagnosis and surveillance of bladder cancer.

  14. MIM, a Potential Metastasis Suppressor Gene in Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Young-Goo Lee

    2002-01-01

    Full Text Available Using a modified version of the mRNA differential display technique, five human bladder cancer cell lines from low grade to metastatic were analyzed to identify differences in gene expression. A 316-bp cDNA (C11300 was isolated that was not expressed in the metastatic cell line TccSuP. Sequence analysis revealed that this gene was identical to KIAA 0429, has a 5.3-kb transcript that mapped to 8824.1. The protein is predicted to be 356 amino acids in size and has an actin-binding WH2 domain. Northern blot revealed expression in multiple normal tissues, but none in a metastatic breast cancer cell line (SKBR3 or in metastatic prostatic cancer cell lines (LNCaP, PC3. We have named this gene Missing in Metastasis (MIM and our data suggest that it may be involved in cytoskeletal organization.

  15. Molecular genetics and genomics progress in urothelial bladder cancer.

    Science.gov (United States)

    Netto, George J

    2013-11-01

    The clinical management of solid tumor patients has recently undergone a paradigm shift as the result of the accelerated advances in cancer genetics and genomics. Molecular diagnostics is now an integral part of routine clinical management in lung, colon, and breast cancer patients. In a disappointing contrast, molecular biomarkers remain largely excluded from current management algorithms of urologic malignancies. The need for new treatment alternatives and validated prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management is pressing. Identifying robust predictive biomarkers that can stratify response to newly introduced targeted therapeutics is another crucially needed development. The following is a brief discussion of some promising candidate biomarkers that may soon become a part of clinical management of bladder cancers.

  16. Role of hexaminolevulinate-guided fluorescence cystoscopy in bladder cancer

    DEFF Research Database (Denmark)

    Malmström, Per-Uno; Grabe, Magnus; Haug, Erik Skaaheim;

    2012-01-01

    Hexaminolevulinate (HAL) is an optical imaging agent used with fluorescence cystoscopy (FC) for the detection of non-muscle-invasive bladder cancer (NMIBC). Guidelines from the European Association of Urology (EAU) and a recent, more detailed European expert consensus statement agree that HAL......-FC has a role in improving detection of NMIBC and provide recommendations on situations for its use. Since the publication of the EAU guidelines and the European consensus statement, new evidence on the efficacy of HAL-FC in reducing recurrence of NMIBC, compared with white light cystoscopy (WLC), have...

  17. A study of image-guided radiotherapy of bladder cancer based on lipiodol injection in the bladder wall

    Energy Technology Data Exchange (ETDEWEB)

    Soendergaard, Jimmi; Muren, Ludvig Paul; Elstroem, Ulrik Vindelev; Grau, Cai; Hoeyer, Morten (Dept. of Oncology, Aarhus Univ. Hospital, Aarhus (Denmark)), E-mail: jimmsoen@rm.dk; Oerding Olsen, Kasper (Dept. of Urology, Aarhus Univ. Hospital, Aarhus (Denmark))

    2010-10-15

    Purpose. We have tested a procedure of focal injection of the contrast medium Lipiodol as a fiducial marker for image-guided boost of the tumor in bladder cancer radiotherapy (RT). In this study, we have evaluated the feasibility and the safety of the method as well as the inter- and intra-fraction shift of the bladder tumor. Materials and methods. Five patients with muscle invasive urinary bladder cancer were included in the study. Lipiodol was injected during flexible cystoscopy into the submucosa of the bladder wall at the periphery of the tumor or the post resection tumor-bed. Cone-beam CT (CBCT) scans were acquired daily throughout the course of RT. Results. Lipiodol demarcation of the bladder tumor was feasible and safe with only a minimum of side effects related to the procedure. The Lipiodol spots were visible on CT and CBCT scans for the duration of the RT course. More than half of all the treatment fractions required a geometric shift of 5 mm or more to match on the Lipiodol spots. The mean intra-fraction shift (3D) of the tumor was 3 mm, largest in the anterior-posterior and cranial-caudal directions. Conclusion. This study demonstrates that Lipiodol can be injected into the bladder mucosa and subsequently visualized on CT and CBCT as a fiducial marker. The relatively large inter-fraction shifts in the positions of Lipiodol spots compared to the intra-fraction movement indicates that image-guided RT based on radio-opaque markers is important for RT of the bladder cancer tumor.

  18. P53 and Cancer-Associated Sialylated Glycans Are Surrogate Markers of Cancerization of the Bladder Associated with Schistosoma haematobium Infection

    Science.gov (United States)

    Lima, Luís; Tavares, Ana; Peixoto, Andreia; Parreira, Beatriz; Correia da Costa, José Manuel; Brindley, Paul J.; Lopes, Carlos

    2014-01-01

    in the healthy urothelium. Conclusion/Significance This preliminary study suggests that p53 and sialylated glycans are surrogate biomarkers of bladder cancerization associated with S. haematobium, highlighting a missing link between infection and cancer development. Eggs of S. haematobium express sLea and sLex antigens in mimicry of human leukocytes glycosylation, which may play a role in the colonization and disease dissemination. These observations may help the early identification of infected patients at a higher risk of developing bladder cancer and guide the future development of non-invasive diagnostic tests. PMID:25502795

  19. P53 and cancer-associated sialylated glycans are surrogate markers of cancerization of the bladder associated with Schistosoma haematobium infection.

    Directory of Open Access Journals (Sweden)

    Júlio Santos

    2014-12-01

    .This preliminary study suggests that p53 and sialylated glycans are surrogate biomarkers of bladder cancerization associated with S. haematobium, highlighting a missing link between infection and cancer development. Eggs of S. haematobium express sLea and sLex antigens in mimicry of human leukocytes glycosylation, which may play a role in the colonization and disease dissemination. These observations may help the early identification of infected patients at a higher risk of developing bladder cancer and guide the future development of non-invasive diagnostic tests.

  20. Radical cystectomy with or without prior irradiation in the treatment of bladder cancer.

    Science.gov (United States)

    Whitmore, W F; Batata, M A; Ghoneim, M A; Grabstald, H; Unal, A

    1977-01-01

    This is a summary presentation on certain aspects of an experience with the use of radical cystectomy with or without prior irradiation in the treatment of selected patients with bladder cancer at the Memorial Sloan-Kettering Cancer Center.

  1. A case-control study of bladder cancer using city directories as a source of occupational data.

    Science.gov (United States)

    Steenland, K; Burnett, C; Osorio, A M

    1987-08-01

    Commercial city directories, currently produced in 1,250 United States cities, potentially provide yearly information on occupation and employer for all city residents over age 18 years. To investigate the usefulness of these occupational data, the authors have conducted a case-control study of male bladder cancer mortality in Hamilton County, Ohio (which includes Cincinnati). A total of 731 bladder cancer cases who died during 1960-1982 were matched on age, sex, race, date-of-death, and residence at death to two controls per case. Risks of bladder cancer death were calculated by occupation, industry, and specific employer, using both city directories (multiple statements) and death certificates (single statement). Four companies showed a significant excess bladder cancer risk when using city directories. Only one would have been identified using death certificates, which ask for usual lifetime type of industry rather than a specific company name. Using city directories, significant positive associations were found between bladder cancer and occupation as an engineer, tailor, carpenter, furnace operator, blending machine operator, chemist, pressing machine operator, house cleaner, or salesman. For industry, the authors found significant positive associations for the textile, chemical, grain mill, foundry, petroleum, building service, entertainment, and advertising industries. A significant increase in risk for those with 20 or more years of employment was seen for those employed as truck drivers and furnace operators, or those employed in the railroad industry. A check of the validity of city directory data indicated that 77 per cent of the listings agreed with Social Security earnings reports for employer in any given year. One limitation of Hamilton County city directory data was the fairly large number of yearly listings without any occupational data (15 per cent for occupation, 36 per cent for employer). While city directory data do provide work history over

  2. Occupation, tobacco use, coffee, and bladder cancer in the county of Mataro (Spain).

    Science.gov (United States)

    González, C A; Lopez-Abente, G; Errezola, M; Castejón, J; Estrada, A; Garcia-Milá, M; Gili, P; Huguet, M; Serrat, M; Soler, F

    1985-05-01

    This report presents the results of an epidemiologic case-control study. The study includes 58 cases and 116 controls from both sexes, selected from the Admission Register of the Hospital and from the Death Registry Office of the local city authorities. Controls have been matched to cases by age, sex, place of residence and source of selection. The results demonstrated no increased risk associated with coffee consumption. Habitual smokers present a 2.3 times higher risk than nonsmokers. The estimated relative risk for occupation standardized by age and smoking habit, is 5.5. A multiplicative effect of the simultaneous action of smoking and occupational exposure has been observed to be an estimated relative risk of 11.7. The attributable risk of the population has been estimated to be 39% for smokers and 12% for occupational exposure. A strong association was found between bladder cancer and occupational exposure to carcinogenic substances, especially in the dye and print textile industries.

  3. Endoscopic gold fiducial marker placement into the bladder wall to optimize radiotherapy targeting for bladder-preserving management of muscle-invasive bladder cancer: feasibility and initial outcomes.

    Directory of Open Access Journals (Sweden)

    Maurice M Garcia

    Full Text Available BACKGROUND AND PURPOSE: Bladder radiotherapy is a management option for carefully selected patients with muscle-invasive bladder cancer. However, the inability to visualize the tumor site during treatment and normal bladder movement limits targeting accuracy and increases collateral radiation. A means to accurately and reliably target the bladder during radiotherapy is needed. MATERIALS AND METHODS: Eighteen consecutive patients with muscle-invasive bladder cancer (T1-T4 elected bladder-preserving treatment with maximal transurethral resection (TUR, radiation and concurrent chemotherapy. All underwent endoscopic placement of 24-K gold fiducial markers modified with micro-tines (70 [2.9×0.9 mm.]; 19 [2.1×0.7 mm. into healthy submucosa 5-10 mm. from the resection margin, using custom-made coaxial needles. Marker migration was assessed for with intra-op bladder-filling cystogram and measurement of distance between markers. Set-up error and marker retention through completion of radiotherapy was confirmed by on-table portal imaging. RESULTS: Between 1/2007 and 7/2012, a total of 89 markers (3-5 per tumor site were placed into 18 patients of mean age 73.6 years. Two patients elected cystectomy before starting treatment; 16/18 completed chemo-radiotherapy. All (100% markers were visible with all on-table (portal, cone-beam CT, fluoroscopy, plain-film, and CT-scan imaging. In two patients, 1 of 4 markers placed at the tumor site fell-out (voided during the second half of radiotherapy. All other markers (80/82, 98% were present through the end of radio-therapy. No intraoperative (e.g. uncontrolled bleeding, collateral injury or post-operative complications (e.g. stone formation, urinary tract infection, post-TUR hematuria >48 hours occurred. Use of micro-tined fiducial tumor-site markers afforded a 2 to 6-fold reduction in bladder-area targeted with high-dose radiation. DISCUSSION: Placement of the micro-tined fiducial markers into the bladder was

  4. Understanding the molecular pathogenesis and prognostics of bladder cancer: an overview.

    Science.gov (United States)

    Zhao, Ming; He, Xiang-Lei; Teng, Xiao-Dong

    2016-02-01

    The knowledge of cellular mechanisms in malignances of the bladder has grown exponentially. Molecular technologies have led to the discovery of the molecular pathways distinguishing low-and high-grade urothelial neoplasms. This trend portends the future in which the classification and diagnosis of the bladder tumors through morphologic analysis will be supported by molecular information correlating with prognosis and targeted therapy. This article outlines tumor molecular pathology of bladder cancer with an emphasis on several promising candidate biomarkers that may soon make their transition to the realm of clinical management of bladder cancer.

  5. Risks of Prostate Cancer Screening

    Science.gov (United States)

    ... prostate may be similar to symptoms of prostate cancer . Enlarge Normal prostate and benign prostatic hyperplasia (BPH). A normal prostate does not block the flow of urine from the bladder. An enlarged prostate presses on the bladder and urethra and blocks the flow of urine. See the ...

  6. Incidence of Bladder Cancer in Sri Lanka: Analysis of the Cancer Registry Data and Review of the Incidence of Bladder Cancer in the South Asian Population

    Science.gov (United States)

    De Silva, Daswin; De Silva, M.V.C.; Ranasinghe, Tamra I J; Lawrentschuk, Nathan; Bolton, Damien; Persad, Raj

    2012-01-01

    Purpose To investigate the incidence of bladder cancer (BC) in Sri Lanka and to compare risk factors and outcomes with those of other South Asian nations and South Asian migrants to the United Kingdom (UK) and the United States (US). Materials and Methods The incidence of BC in Sri Lanka was examined by using two separate cancer registry databases over a 5-year period. Smoking rates were compiled by using a population-based survey from 2001 to 2009 and the relative risk was calculated by using published data. Results A total of 637 new cases of BC were diagnosed over the 5-year period. Sri Lankan BC incidence increased from 1985 but remained low (1.36 and 0.3 per 100,000 in males and females) and was similar to the incidence in other South Asian countries. The incidence was lower, however, than in migrant populations in the US and the UK. In densely populated districts of Sri Lanka, these rates almost doubled. Urothelial carcinoma accounted for 72%. The prevalence of male smokers in Sri Lanka was 39%, whereas Pakistan had higher smoking rates with a 6-fold increase in BC. Conclusions Sri Lankan BC incidence was low, similar to other South Asian countries (apart from Pakistan), but the actual incidence is likely higher than the cancer registry rates. Smoking is likely to be the main risk factor for BC. Possible under-reporting in rural areas could account for the low rates of BC in Sri Lanka. Any genetic or environmental protective effects of BC in South Asians seem to be lost on migration to the UK or the US and with higher levels of smoking, as seen in Pakistan. PMID:22670188

  7. DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection

    Directory of Open Access Journals (Sweden)

    Goldberg José

    2008-08-01

    Full Text Available Abstract Background Epigenetic alterations are a hallmark of human cancer. In this study, we aimed to investigate whether aberrant DNA methylation of cancer-associated genes is related to urinary bladder cancer recurrence. Methods A set of 4 genes, including CDH1 (E-cadherin, SFN (stratifin, RARB (retinoic acid receptor, beta and RASSF1A (Ras association (RalGDS/AF-6 domain family 1, had their methylation patterns evaluated by MSP (Methylation-Specific Polymerase Chain Reaction analysis in 49 fresh urinary bladder carcinoma tissues (including 14 cases paired with adjacent normal bladder epithelium, 3 squamous cell carcinomas and 2 adenocarcinomas and 24 cell sediment samples from bladder washings of patients classified as cancer-free by cytological analysis (control group. A third set of samples included 39 archived tumor fragments and 23 matched washouts from 20 urinary bladder cancer patients in post-surgical monitoring. After genomic DNA isolation and sodium bisulfite modification, methylation patterns were determined and correlated with standard clinic-histopathological parameters. Results CDH1 and SFN genes were methylated at high frequencies in bladder cancer as well as in paired normal adjacent tissue and exfoliated cells from cancer-free patients. Although no statistically significant differences were found between RARB and RASSF1A methylation and the clinical and histopathological parameters in bladder cancer, a sensitivity of 95% and a specificity of 71% were observed for RARB methylation (Fisher's Exact test (p RASSF1A gene, respectively, in relation to the control group. Conclusion Indistinct DNA hypermethylation of CDH1 and SFN genes between tumoral and normal urinary bladder samples suggests that these epigenetic features are not suitable biomarkers for urinary bladder cancer. However, RARB and RASSF1A gene methylation appears to be an initial event in urinary bladder carcinogenesis and should be considered as defining a panel of

  8. A departmental audit of patients with bladder cancer.

    Science.gov (United States)

    Sahabudin, R. M.; Persad, R. A.; Mishriki, F.; Feneley, R. C.

    1992-01-01

    In keeping with the recent demands of the Department of Health for medical audit in clinical practice, an audit was undertaken of the management of bladder cancer patients in a large department of urology having three consultants with varied approaches of management. This study revealed interesting controversial areas for further scrutiny. For example, the poor prognosis of grade 3 T1 tumours with and without associated carcinoma-in-situ (CIS) and the speed of progression to invasive disease have indicated that a change to a more aggressive approach to the management of these tumours is necessary. High recurrence rates at the site of the original tumour (60%) and the presence of CIS also indicate the need for expert and thorough initial tumour assessment. The delays in diagnosis and treatment lend further support to the need for a 'haematuria clinic' to minimise such delays, which may influence prognosis. To reduce the occurrence of systematic errors in the recording, follow-up and surveillance of patients with bladder cancer, a protocol is suggested for a structured approach to optimise results, particularly in the poor prognostic categories. PMID:1416708

  9. The Immediate Results of Surgical Treatment of Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Alexei L. Charyshkin

    2016-06-01

    Full Text Available The objective of this study was to evaluate the immediate results of the use of ureterointestinal anastomosis according to the Bricker technique at radical cystectomy (RC for bladder cancer (BC. Materials and Results: The study included 96 patients (11.5% women and 88.5% men with bladder cancer (BC, aged from 31 to 74 years (mean age 63.8±7.2, who underwent RC in the Lipetsk Regional Oncology Center, in the period from 2005 to 2014. Among the early postoperative complications, we identified dynamic ileus (16.7%, inflammatory complications of the surgical wound (12.5%, acute pyelonephritis (10.4%, and failure of ureterointestinal anastomosis (4.2%. The frequency of postoperative acute pyelonephritis corresponded to the findings of other authors. Two (2.1% patients died from early postoperative complications because of concomitant diseases (ischemic heart disease, myocardial infarction; thus, postoperative mortality in the early postoperative period was 4.2%. Chronic pyelonephritis with chronic renal failure detected in 15(15.6% patients after one year after surgery was the most frequent late postoperative complication. The stricture of ureterointestinal anastomosis in 9(9.4% patients has been eliminated through relaparotomy and resection of anastomosis. The development of urolithiasis in 12(12.5% patients after one year after surgery has required the implementation of contact lithotripsy and litholytic therapy.

  10. Effect of sirolimus on urinary bladder cancer T24 cell line

    Directory of Open Access Journals (Sweden)

    Oliveira Paula A

    2009-01-01

    Full Text Available Abstract Background Sirolimus is recently reported to have antitumour effects on a large variety of cancers. The present study was performed to investigate sirolimus's ability to inhibit growth in T24 bladder cancer cells. Methods T24 bladder cancer cells were treated with various concentrations of sirolimus. MTT assay was used to evaluate the proliferation inhibitory effect on T24 cell line. The viability of T24 cell line was determined by Trypan blue exclusion analysis. Results Sirolimus inhibits the growth of bladder carcinoma cells and decreases their viability. Significant correlations were found between cell proliferation and sirolimus concentration (r = 0.830; p Conclusion Sirolimus has an anti-proliferation effect on the T24 bladder carcinoma cell line. The information from our results is useful for a better understanding sirolimus's anti-proliferative activity in the T24 bladder cancer cell line.

  11. Identification of differentially expressed proteins during human urinary bladder cancer progression

    DEFF Research Database (Denmark)

    Memon, Ashfaque Ahmed; chang, Jong. w; Oh, Bong R.

    2005-01-01

    Comparative proteome analysis was performed between RT4 (grade-1) and T24 (grade-3) bladder cancer cell lines, in an attempt to identify differentially expressed proteins during bladder cancer progression. Among those relatively abundant proteins, seven spots changed more than two-fold reproducibly...... cancer cell line. Subsequent Western blotting analysis of human biopsy samples from bladder cancer patient revealed significant loss of IDPc and Prx-II in more advance tumor samples, in agreement with data on cell lines. These results suggest that loss of IDPc and Prx-II during tumor development may...

  12. Intra-arterial chemotherapy in combination with radiotherapy for invasive bladder cancer and prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sumiyoshi, Yoshiteru; Hashine, Katsuyoshi; Nakatsuji, Hiroyoshi [National Shikoku Cancer Center Hospital, Matsuyama (Japan)

    1999-02-01

    Forty-five patients with muscle-invasive bladder cancer treated with intra-arterial doxorubicin chemotherapy plus low-dose radiotherapy between September 1979 and March 1990 were retrospectively studied. Twenty-eight (62%) patients achieved a complete response (CR) and in all of them, a functional bladder could be preserved. The 10-year cause-specific survival rate of patients with CR was 95.5%, but that of patients not achieving a CR was 39%. These results demonstrate that in patients who achieve a CR with this treatment, we may be able to preserve a functional bladder. In a prospective study, we designed a new intra-arterial chemotherapy regimen in order to achieve a higher degree of effectiveness and to preserve a functional bladder. Twenty-three patients were treated with concurrent pirarubicin/cisplatin intra-arterial chemotherapy and radiotherapy after complete transurethral resection. Twenty-one (91%) patients achieved CR. One of these patients had relapse with lung metastases and was treated surgically. Two patients who did not achieve a CR died of cancer, and 21 patients are alive with preservation of functional bladder. For treatment of prostate cancer, we now administer only adjuvant intra-arterial chemotherapy plus irradiation for patients after radical prostatectomy. (author)

  13. EZH2 in Bladder Cancer, a Promising Therapeutic Target

    Directory of Open Access Journals (Sweden)

    Mónica Martínez-Fernández

    2015-11-01

    Full Text Available Bladder Cancer (BC represents a current clinical and social challenge. The recent studies aimed to describe the genomic landscape of BC have underscored the relevance of epigenetic alterations in the pathogenesis of these tumors. Among the epigenetic alterations, histone modifications occupied a central role not only in cancer, but also in normal organism homeostasis and development. EZH2 (Enhancer of Zeste Homolog 2 belongs to the Polycomb repressive complex 2 as its catalytic subunit, which through the trimethylation of H3 (Histone 3 on K27 (Lysine 27, produces gene silencing. EZH2 is frequently overexpressed in multiple tumor types, including BC, and plays multiple roles besides the well-recognized histone mark generation. In this review, we summarize the present knowledge on the oncogenic roles of EZH2 and its potential use as a therapeutic target, with special emphasis on BC pathogenesis and management.

  14. Discrimination of healthy and cancer cells of the bladder by metabolic state, based on autofluorescence

    Science.gov (United States)

    Palmer, S.; Litvinova, Karina; Rafailov, E. U.; Nabi, G.

    2015-02-01

    Bladder cancer is among the most common cancers worldwide (4th in men). It is responsible for high patient morbidity and displays rapid recurrence and progression. Lack of sensitivity of gold standard techniques (white light cystoscopy, voided urine cytology) means many early treatable cases are missed. The result is a large number of advanced cases of bladder cancer which require extensive treatment and monitoring. For this reason, bladder cancer is the single most expensive cancer to treat on a per patient basis. In recent years, autofluorescence spectroscopy has begun to shed light into disease research. Of particular interest in cancer research are the fluorescent metabolic cofactors NADH and FAD. Early in tumour development, cancer cells often undergo a metabolic shift (the Warburg effect) resulting in increased NADH. The ratio of NADH to FAD ("redox ratio") can therefore be used as an indicator of the metabolic status of cells. Redox ratio measurements have been used to differentiate between healthy and cancer breast cells and to monitor cellular responses to therapies. Here, we have demonstrated, using healthy and bladder cancer cell lines, a statistically significant difference in the redox ratio of bladder cancer cells, indicative of a metabolic shift. To do this we customised a standard flow cytometer to excite and record fluorescence specifically from NADH and FAD, along with a method for automatically calculating the redox ratio of individual cells within large populations. These results could inform the design of novel probes and screening systems for the early detection of bladder cancer.

  15. Treatment results of radiation therapy for muscle-invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Langsenlehner, Tanja; Doeller, Carmen; Stranzl-Lawatsch, Heidi; Kapp, Karin S. [Univ. Clinic of Therapeutic Radiology and Oncology, Medical Univ. of Graz (Austria); Quehenberger, Franz [Inst. for Medical Informatics, Statistics and Documentation, Medical Univ. of Graz (Austria); Langsenlehner, Uwe [Internal Outpatient Dept., Steiermaerkische GKK, Graz (Austria); Pummer, Karl [Dept. of Urology, Medical Univ. of Graz (Austria)

    2010-04-15

    Purpose: To assess local control and survival rates in patients with muscle-invasive bladder cancer treated with external-beam radiotherapy and to investigate prognostic factors. Patients and methods: Between 1997 and 2007, 75 patients (male, n = 58; female, n = 17, median age, 74.2 years) with localized transitional cell carcinoma of the bladder (T2, n = 34; T3, n = 32; T4, n = 9) not suitable for radical surgery due to advanced age, comorbidity or inoperability underwent external-beam radiotherapy without simultaneous chemotherapy at the University Clinic of Therapeutic Radiology and Oncology, Medical University of Graz, Austria. A conformal four-field technique was used in all patients to treat the tumor and regional lymph nodes with single daily fractions of 1.8-2 Gy to a total dose of 50-50.4 Gy, followed by a cone-down to encompass the empty bladder which was boosted to 70-70.4 Gy. All patients had undergone transurethral tumor resection prior to radiotherapy which was macroscopically incomplete in 62 patients. Results: Complete response was achieved in 65% of patients. Actuarial 3-year local control and metastases-free survival rates were 52.5% and 63.7%, 3-year local recurrence-free survival rate in complete responders was 71%. In univariate analysis, hydronephrosis, lymph vessel invasion, and macroscopic residual tumor were significantly predictive of disease progression. Hydronephrosis and lymph vessel invasion were also associated with a higher risk of local recurrence. The actuarial 3-year progression-free and overall survival rates were 40.1% and 56.9%, respectively. Conclusion: Radiotherapy is an effective treatment option in terms of local control and survival even in elderly patients with locally advanced bladder cancer not suitable for cystectomy. (orig.)

  16. ADAM15 Is Functionally Associated with the Metastatic Progression of Human Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Guadalupe Lorenzatti Hiles

    Full Text Available ADAM15 is a member of a family of catalytically active disintegrin membrane metalloproteinases that function as molecular signaling switches, shed membrane bound growth factors and/or cleave and inactivate cell adhesion molecules. Aberrant metalloproteinase function of ADAM15 may contribute to tumor progression through the release of growth factors or disruption of cell adhesion. In this study, we utilized human bladder cancer tissues and cell lines to evaluate the expression and function of ADAM15 in the progression of human bladder cancer. Examination of genome and transcriptome databases revealed that ADAM15 ranked in the top 5% of amplified genes and its mRNA was significantly overexpressed in invasive and metastatic bladder cancer compared to noninvasive disease. Immunostaining of a bladder tumor tissue array designed to evaluate disease progression revealed increased ADAM15 immunoreactivity associated with increasing cancer stage and exhibited significantly stronger staining in metastatic samples. About half of the invasive tumors and the majority of the metastatic cases exhibited high ADAM15 staining index, while all low grade and noninvasive cases exhibited negative or low staining. The knockdown of ADAM15 mRNA expression significantly inhibited bladder tumor cell migration and reduced the invasive capacity of bladder tumor cells through MatrigelTM and monolayers of vascular endothelium. The knockdown of ADAM15 in a human xenograft model of bladder cancer inhibited tumor growth by 45% compared to controls. Structural modeling of the catalytic domain led to the design of a novel ADAM15-specific sulfonamide inhibitor that demonstrated bioactivity and significantly reduced the viability of bladder cancer cells in vitro and in human bladder cancer xenografts. Taken together, the results revealed an undescribed role of ADAM15 in the invasion of human bladder cancer and suggested that the ADAM15 catalytic domain may represent a viable

  17. Risk-optimized proton therapy to minimize radiogenic second cancers

    DEFF Research Database (Denmark)

    Rechner, Laura A; Eley, John G; Howell, Rebecca M

    2015-01-01

    Proton therapy confers substantially lower predicted risk of second cancer compared with photon therapy. However, no previous studies have used an algorithmic approach to optimize beam angle or fluence-modulation for proton therapy to minimize those risks. The objectives of this study were...... to demonstrate the feasibility of risk-optimized proton therapy and to determine the combination of beam angles and fluence weights that minimizes the risk of second cancer in the bladder and rectum for a prostate cancer patient. We used 6 risk models to predict excess relative risk of second cancer. Treatment...

  18. An Epigenomic Approach to Improving Response to Neoadjuvant Cisplatin Chemotherapy in Bladder Cancer.

    Science.gov (United States)

    Xylinas, Evanguelos; Hassler, Melanie R; Zhuang, Dazhong; Krzywinski, Martin; Erdem, Zeynep; Robinson, Brian D; Elemento, Olivier; Clozel, Thomas; Shariat, Shahrokh F

    2016-09-02

    Bladder cancer is among the five most common cancers diagnosed in the Western world and causes significant mortality and morbidity rates in affected patients. Therapeutic options to treat the disease in advanced muscle-invasive bladder cancer (MIBC) include cystectomy and chemotherapy. Neoadjuvant cisplatin-based combination chemotherapy is effective in MIBC; however, it has not been widely adopted by the community. One reason is that many patients do not respond to neoadjuvant chemotherapy, and no biomarker currently exists to identify these patients. It is also not clear whether a strategy to sensitize chemoresistant patients may exist. We sought to identify cisplatin-resistance patterns in preclinical models of bladder cancer, and test whether treatment with the epigenetic modifier decitabine is able to sensitize cisplatin-resistant bladder cancer cell lines. Using a screening approach in cisplatin-resistant bladder cancer cell lines, we identified dysregulated genes by RNA sequencing (RNAseq) and DNA methylation assays. DNA methylation analysis of tumors from 18 patients receiving cisplatin-based chemotherapy was used to confirm in vitro results. Cisplatin-resistant bladder cancer cells were treated with decitabine to investigate epigenetic sensitization of resistant cell lines. Our results show that HOXA9 promoter methylation status is associated with response to cisplatin-based chemotherapy in bladder cancer cell lines and in metastatic bladder cancer. Bladder cancer cells resistant to cisplatin chemotherapy can be sensitized to cisplatin by the DNA methylation inhibitor decitabine. Our data suggest that HOXA9 promoter methylation could serve as potential predictive biomarker and decitabine might sensitize resistant tumors in patients receiving cisplatin-based chemotherapy.

  19. An Epigenomic Approach to Improving Response to Neoadjuvant Cisplatin Chemotherapy in Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Evanguelos Xylinas

    2016-09-01

    Full Text Available Bladder cancer is among the five most common cancers diagnosed in the Western world and causes significant mortality and morbidity rates in affected patients. Therapeutic options to treat the disease in advanced muscle-invasive bladder cancer (MIBC include cystectomy and chemotherapy. Neoadjuvant cisplatin-based combination chemotherapy is effective in MIBC; however, it has not been widely adopted by the community. One reason is that many patients do not respond to neoadjuvant chemotherapy, and no biomarker currently exists to identify these patients. It is also not clear whether a strategy to sensitize chemoresistant patients may exist. We sought to identify cisplatin-resistance patterns in preclinical models of bladder cancer, and test whether treatment with the epigenetic modifier decitabine is able to sensitize cisplatin-resistant bladder cancer cell lines. Using a screening approach in cisplatin-resistant bladder cancer cell lines, we identified dysregulated genes by RNA sequencing (RNAseq and DNA methylation assays. DNA methylation analysis of tumors from 18 patients receiving cisplatin-based chemotherapy was used to confirm in vitro results. Cisplatin-resistant bladder cancer cells were treated with decitabine to investigate epigenetic sensitization of resistant cell lines. Our results show that HOXA9 promoter methylation status is associated with response to cisplatin-based chemotherapy in bladder cancer cell lines and in metastatic bladder cancer. Bladder cancer cells resistant to cisplatin chemotherapy can be sensitized to cisplatin by the DNA methylation inhibitor decitabine. Our data suggest that HOXA9 promoter methylation could serve as potential predictive biomarker and decitabine might sensitize resistant tumors in patients receiving cisplatin-based chemotherapy.

  20. Concurrent chemoradiotherapy improves survival outcome in muscle-invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Sang Jun; Kim, Jin Hee; Oh, Young Kee; Kim, Byung Hoon [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2015-12-15

    To evaluate survival rates and prognostic factors related to treatment outcomes after bladder preserving therapy including transurethral resection of bladder tumor, radiotherapy (RT) with or without concurrent chemotherapy in bladder cancer with a curative intent. We retrospectively studied 50 bladder cancer patients treated with bladder-preserving therapy at Keimyung University Dongsan Medical Center from January 1999 to December 2010. Age ranged from 46 to 89 years (median, 71.5 years). Bladder cancer was the American Joint Committee on Cancer (AJCC) stage II, III, and IV in 9, 27, and 14 patients, respectively. Thirty patients were treated with concurrent chemoradiotherapy (CCRT) and 20 patients with RT alone. Nine patients received chemotherapy prior to CCRT or RT alone. Radiation was delivered with a four-field box technique (median, 63 Gy; range, 48.6 to 70.2 Gy). The follow-up periods ranged from 2 to 169 months (median, 34 months). Thirty patients (60%) showed complete response and 13 (26%) a partial response. All patients could have their own bladder preserved. Five-year overall survival (OS) rate was 37.2%, and the 5-year disease-free survival (DFS) rate was 30.2%. In multivariate analysis, tumor grade and CCRT were statistically significant in OS. Tumor grade was a significant prognostic factor related to OS. CCRT is also considered to improve survival outcomes. Further multi-institutional studies are needed to elucidate the impact of RT in bladder cancer.

  1. Pancreatic Cancer Risk Factors

    Science.gov (United States)

    ... risks of other cancers (or other health problems). Examples of genetic syndromes that can cause exocrine pancreatic cancer include: Hereditary breast and ovarian cancer syndrome , caused by mutations in the BRCA1 or BRCA2 genes Familial atypical ...

  2. Toxicogenetic profile and cancer risk in Lebanese.

    Science.gov (United States)

    Dhaini, Hassan R; Kobeissi, Loulou

    2014-01-01

    An increasing number of genetic polymorphisms in drug-metabolizing enzymes (DME) were identified among different ethnic groups. Some of these polymorphisms are associated with an increased cancer risk, while others remain equivocal. However, there is sufficient evidence that these associations become significant in populations overexposed to environmental carcinogens. Hence, genetic differences in expression activity of both Phase I and Phase II enzymes may affect cancer risk in exposed populations. In Lebanon, there has been a marked rise in reported cancer incidence since the 1990s. There are also indicators of exposure to unusually high levels of environmental pollutants and carcinogens in the country. This review considers this high cancer incidence by exploring a potential gene-environment model based on available DME polymorphism prevalence, and their impact on bladder, colorectal, prostate, breast, and lung cancer in the Lebanese population. The examined DME include glutathione S-transferases (GST), N-acetyltransferases (NAT), and cytochromes P-450 (CYP). Data suggest that these DME influence bladder cancer risk in the Lebanese population. Evidence indicates that identification of a gene-environment interaction model may help in defining future research priorities and preventive cancer control strategies in this country, particularly for breast and lung cancer.

  3. Occult Pelvic Lymph Node Involvement in Bladder Cancer: Implications for Definitive Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Goldsmith, Benjamin; Baumann, Brian C.; He, Jiwei; Tucker, Kai; Bekelman, Justin; Deville, Curtiland; Vapiwala, Neha [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vaughn, David; Keefe, Stephen M. [Department of Medical Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Guzzo, Thomas; Malkowicz, S. Bruce [Department of Urology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Christodouleas, John P., E-mail: christojo@uphs.upenn.edu [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2014-03-01

    Purpose: To inform radiation treatment planning for clinically staged, node-negative bladder cancer patients by identifying clinical factors associated with the presence and location of occult pathologic pelvic lymph nodes. Methods and Materials: The records of patients with clinically staged T1-T4N0 urothelial carcinoma of the bladder undergoing radical cystectomy and pelvic lymphadenectomy at a single institution were reviewed. Logistic regression was used to evaluate associations between preoperative clinical variables and occult pathologic pelvic or common iliac lymph nodes. Percentages of patient with involved lymph node regions entirely encompassed within whole bladder (perivesicular nodal region), small pelvic (perivesicular, obturator, internal iliac, and external iliac nodal regions), and extended pelvic clinical target volume (CTV) (small pelvic CTV plus common iliac regions) were calculated. Results: Among 315 eligible patients, 81 (26%) were found to have involved pelvic lymph nodes at the time of surgery, with 38 (12%) having involved common iliac lymph nodes. Risk of occult pathologically involved lymph nodes did not vary with clinical T stage. On multivariate analysis, the presence of lymphovascular invasion (LVI) on preoperative biopsy was significantly associated with occult pelvic nodal involvement (odds ratio 3.740, 95% confidence interval 1.865-7.499, P<.001) and marginally associated with occult common iliac nodal involvement (odds ratio 2.307, 95% confidence interval 0.978-5.441, P=.056). The percentages of patients with involved lymph node regions entirely encompassed by whole bladder, small pelvic, and extended pelvic CTVs varied with clinical risk factors, ranging from 85.4%, 95.1%, and 100% in non-muscle-invasive patients to 44.7%, 71.1%, and 94.8% in patients with muscle-invasive disease and biopsy LVI. Conclusions: Occult pelvic lymph node rates are substantial for all clinical subgroups, especially patients with LVI on biopsy. Extended

  4. JNK2 downregulation promotes tumorigenesis and chemoresistance by decreasing p53 stability in bladder cancer

    Science.gov (United States)

    Zhao, Yu; Qian, Chenchen; Wang, Liguo; Qi, Jun

    2016-01-01

    Bladder cancer is one of the most common malignancies of the urinary system, and the 5-year survival rate remains low. A comprehensive understanding of the carcinogenesis and progression of bladder cancer is urgently needed to advance treatment. c-Jun N-terminal kinase-2 (JNK2) exhibits both tumor promoter and tumor suppressor actions, depending on tumor type. Here, we analyzed the JNK2 function in bladder cancer. Using gene expression microarrays, we demonstrated that JNK2 mRNA is downregulated in an orthotopic rat model of bladder cancer. JNK2 protein levels were lower in rat and human bladder cancer tissues than in normal tissues, and the levels correlated with those of p53. Moreover, JNK2 phosphorylated p53 at Thr-81, thus protecting p53 from MDM2-induced proteasome degradation. Decreased expression of JNK2 in T24 cells conferred resistance to cell death induced by mitomycin C. Furthermore, lower JNK2 expression was associated with poorer overall survival among patients who underwent radical cystectomy. These results indicate that JNK2 acts as a tumor suppressor in bladder cancer, and that decreased JNK2 expression promotes bladder cancer tumorigenesis. PMID:27147566

  5. [Peculiarities of urinary bladder cancer tumor cells apoptosis response on neoadjuvant chemotherapy].

    Science.gov (United States)

    Iatsyna, A I; Stakhovskiĭ, É A; Sheremet, Ia A; Spivak, S I; Stakhovskiĭ, A É; Gavriliuk, O N; Vitruk, Iu V; Emets, A I; Blium, Ia B

    2011-01-01

    Induced apoptosis in urinary bladder cancer tumor cells of patients was studied using TUNEL reaction. It was shown that increase in induced apoptosis value had a definite correlation between corresponding features of tumor reaction as a response on Gemcitabine-Cisplatin neoadjuvant chemotherapy application. It was found that evaluation of induced apoptosis in urinary bladder cancer tumor cells using TUNEL method allows forecasting the effectiveness of chemotherapy on the cellular level in patients with this type of cancer.

  6. Animal model of naturally occurring bladder cancer: Characterization of four new canine transitional cell carcinoma cell lines

    OpenAIRE

    Rathore, Kusum; Cekanova, Maria

    2014-01-01

    Background Development and further characterization of animal models for human cancers is important for the improvement of cancer detection and therapy. Canine bladder cancer closely resembles human bladder cancer in many aspects. In this study, we isolated and characterized four primary transitional cell carcinoma (K9TCC) cell lines to be used for future in vitro validation of novel therapeutic agents for bladder cancer. Methods Four K9TCC cell lines were established from naturally-occurring...

  7. Use of Aleuria alantia Lectin Affinity Chromatography to Enrich Candidate Biomarkers from the Urine of Patients with Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Sarah R. Ambrose

    2015-09-01

    Full Text Available Developing a urine test to detect bladder tumours with high sensitivity and specificity is a key goal in bladder cancer research. We hypothesised that bladder cancer-specific glycoproteins might fulfill this role. Lectin-ELISAs were used to study the binding of 25 lectins to 10 bladder cell lines and serum and urine from bladder cancer patients and non-cancer controls. Selected lectins were then used to enrich glycoproteins from the urine of bladder cancer patients and control subjects for analysis by shotgun proteomics. None of the lectins showed a strong preference for bladder cancer cell lines over normal urothlelial cell lines or for urinary glycans from bladder cancer patients over those from non-cancer controls. However, several lectins showed a strong preference for bladder cell line glycans over serum glycans and are potentially useful for enriching glycoproteins originating from the urothelium in urine. Aleuria alantia lectin affinity chromatography and shotgun proteomics identified mucin-1 and golgi apparatus protein 1 as proteins warranting further investigation as urinary biomarkers for low-grade bladder cancer. Glycosylation changes in bladder cancer are not reliably detected by measuring lectin binding to unfractionated proteomes, but it is possible that more specific reagents and/or a focus on individual proteins may produce clinically useful biomarkers.

  8. Renal Function Outcomes and Risk Factors for Stage 3B Chronic Kidney Disease after Urinary Diversion in Patients with Muscle Invasive Bladder Cancer [corrected].

    Directory of Open Access Journals (Sweden)

    Shingo Hatakeyama

    Full Text Available To assess the effects of urinary diversion on renal function, we retrospectively investigated renal function over 5 years after urinary diversion using a propensity score matching strategy.Between May 1996 and November 2013, 345 consecutive adult patients underwent radical cystectomy and urinary diversion in our hospital; one hundred and fifteen patients with more than a 5-year follow-up were enrolled. Propensity scores were calculated using logistic analysis, and the data used in the analyses included age, gender, Eastern Cooperative Oncology Group Performance Status (ECOG-PS, clinical tumor stage, presence of cardiovascular disease; hypertension; and type 2 diabetes and preoperative eGFR at the initial visit. Multivariate logistic regression analysis was used to assess the risk factors for stage 3B chronic kidney disease (CKD after the different types of urinary diversion.Continent and incontinent diversion were performed in 68 and 47 patients, respectively. The mean preoperative eGFR was significantly lower in the incontinent than in the continent group (P < 0.001. In propensity score-matched patients (n = 34 each, no significant differences were observed in pre- and postoperative eGFR and 5-year eGFR decrease rates between the groups. In the incontinent group, the number of postoperative stage 3B CKD patients was significantly increased than the continent group. Using multivariate analysis, independent risk factors significantly associated with stage 3B CKD at 5 years after surgery were older age, eGFR before surgery, incontinent diversion (cutaneous ureterostomy, and postoperative hydronephrosis.The types of urinary diversion had no significant impact on renal function decline, whereas older age, preexisting impaired renal function, postoperative hydronephrosis, and cutaneous ureterostomy were independent risk factors for stage 3B CKD at 5 years after radical cystectomy.

  9. Robotic Radical Cystectomy for Bladder Cancer: Current Perspectives

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    Abdullah Erdem Canda

    2014-05-01

    Full Text Available The most effective local treatment of muscle invasive bladder cancer and non-invasive, high-grade bladder tumours that recur or progress despite intravesical therapies, is open radical cystectomy (RC, extended pelvic lymph node (LN dissection with urinary diversion. Performing these complex procedures using pure laparoscopy is extremely difficult. On the other hand, the surgical robot has the advantage of enabling the console surgeon to perform complex procedures more easily, providing three-dimensional (3D and magnified views, higher grades of wristed hand movements, and decreased hand tremor, while the fourth robotic arm offers additional assistance and tissue retraction which facilitates the learning curve. The number of centres performing robot-assisted radical cystectomy (RARC is increasing. Although most of the centres perform extracorporeal urinary diversion following RARC, very few centres – including ours – have reported their outcomes on RARC with total intracorporeal urinary diversion. Some of the articles, comparing open RC versus RARC, have suggested similar outcomes in terms of operative time, mean LN yield, positive surgical margin (PSM rates, and complication rates, whereas others have suggested decreased estimated blood loss, transfusion rate, complications, length of hospital stay, wound problems, time to flatus, and time to regular diet in the postoperative period in RARC patients. The surgical technique of total intracorporeal RARC with urinary diversions is still evolving, and these complex robotic procedures seem to be technically feasible with good intermediate-term oncologic results, acceptable morbidities, excellent short-term surgical and pathological outcomes, and satisfactory functional results.

  10. Levels of tissue inhibitor of metalloproteinases 1 in plasma and urine frompatients with bladder cancer

    DEFF Research Database (Denmark)

    Holten Andersen, MN; Brunner, N; Nielsen, HJ;

    2006-01-01

    Aim: To assess the potential use of plasma and urine levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) in urothelial cancer. Methods: TIMP-1 levels were determined in urine and plasma from healthy donors (n=26), patients with bacterial bladder infection (n=24), urothelial bladder adenoma...

  11. Hypofractionated Intensity Modulated Radiation Therapy in Combined Modality Treatment for Bladder Preservation in Elderly Patients With Invasive Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Turgeon, Guy-Anne [Department of Oncology, Division of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Souhami, Luis, E-mail: luis.souhami@muhc.mcgill.ca [Department of Oncology, Division of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Cury, Fabio L.; Faria, Sergio L.; Duclos, Marie [Department of Oncology, Division of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Sturgeon, Jeremy [Department of Medical Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Kassouf, Wassim [Department of Urology, McGill University Health Centre, Montreal, Quebec (Canada)

    2014-02-01

    Purpose/Objective(s): To review our experience with bladder-preserving trimodality treatment (TMT) using hypofractionated intensity modulated radiation therapy (IMRT) for the treatment of elderly patients with muscle-invasive bladder cancer. Methods and Materials: Retrospective study of elderly patients treated with TMT using hypofractionated IMRT (50 Gy in 20 fractions) with concomitant weekly radiosensitizing chemotherapy. Eligibility criteria were as follows: age ≥70 years, a proven diagnosis of muscle-invasive transitional cell bladder carcinoma, stage T2-T3N0M0 disease, and receipt of TMT with curative intent. Response rate was assessed by cystoscopic evaluation and bladder biopsy. Results: 24 patients with a median age of 79 years were eligible. A complete response was confirmed in 83% of the patients. Of the remaining patients, 1 of them underwent salvage cystectomy, and no disease was found in the bladder on histopathologic assessment. After a median follow-up time of 28 months, of the patients with a complete response, 2 patients had muscle-invasive recurrence, 1 experienced locoregional failure, and 3 experienced distant metastasis. The overall and cancer-specific survival rates at 3 years were 61% and 71%, respectively. Of the surviving patients, 75% have a disease-free and functioning bladder. All patients completed hypofractionated IMRT, and 19 patients tolerated all 4 cycles of chemotherapy. Acute grade 3 gastrointestinal or genitourinary toxicities occurred in only 4% of the patients, and acute grade 3 or 4 hematologic toxicities, liver toxicities, or both were experienced by 17% of the cohort. No patient experienced grade 4 gastrointestinal or genitourinary toxicity. Conclusions: Hypofractionated IMRT with concurrent radiosensitizing chemotherapy appears to be an effective and well-tolerated curative treatment strategy in the elderly population and should be considered for patients who are not candidates for cystectomy or who wish to avoid

  12. Health-Related Quality of Life after Cystectomy and Urinary Diversion for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Cheryl Shih

    2011-01-01

    Full Text Available With multiple options for urinary diversion after radical cystectomy for bladder cancer that have comparable cancer control and complication rates, health-related quality of life (HRQOL has become an important consideration. This article reviews the methods for defining HRQOL, the challenges in measuring HRQOL in bladder cancer, and the literature comparing HRQOL after various methods of urinary diversion. Recent contributions include the validation of HRQOL instruments specific to bladder cancer and the publication of several prospective studies measuring HRQOL outcomes after cystectomy and urinary diversion. There is no convincing evidence from existing literature that any particular method of urinary diversion offers superior HRQOL outcomes. Rather, there is growing evidence that good HRQOL can be achieved with patient education and consideration of each patient's clinical and psychosocial situation. Future research should utilize the validated bladder cancer specific HRQOL instruments and perhaps explore the impact of preoperative counseling on postoperative HRQOL.

  13. Using of Telomerase Enzyme in Urine as a Non invasive Marker for Cancer Bladder Detection

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    Azza A Hassan*, Fawzia A . El- Sheshtawey** , Seliem A. Seliem

    2008-12-01

    Full Text Available Background: Urinary bladder cancer is one of the major health problem all over the world. Cystoscopy remains the gold standard for identifying bladder cancer but it is invasive and expensive, therefore, a simple, non invasive test for detecting bladder cancer would be helpful. Several biomarkers for bladder cancer have been used, but no single marker has been accurate and conclusive. Aim: The current study aimed to measure telomerase enzyme in urine as a useful non invasive marker for detection of bladder cancer. Methods : Forty eight patients ( 39 males and 9 females were included, They are complaining of urinary symptoms and undergo cystoscopy with biopsy of bladder lesions and histopathological examination. They were divided into groups: Group I: 16 patients ( 11 males and 5 females have benign urologic conditions. Group II: 32 patients (28 males and 4 females have proven bladder cancer patients underwent transurethral resection of bladder tumor or cystoscopy with biopsy of bladder lesions. Also, 15 apparently healthy volunteers with matched age and sex with patients were served as a control group. All subjects were submitted to laboratory estimation of the following in urine: urinary creatinine, urine cytology, telomerase enzyme in urine by telomerase PCR and complete urine examination. Results : The results of this study revealed that a highly significant increase in the frequency of cytolological positive cases for tumor cells in malignant group than each of benign group and healthy subjects, while no significant difference was detected between benign group and healthy subjects. The frequency of telomerase in urine was significantly higher in malignant group than each of benign group and healthy subjects, while no significant difference was detected between benign group and healthy subjects. The telomerase activity has sensitivity of 90.6% for diagnosis of cancer bladder with 93.7% for specificity and PPV was 96.6%, NPV was 83.3% and

  14. Tumor regression grade of urothelial bladder cancer after neoadjuvant chemotherapy: a novel and successful strategy to predict survival.

    Science.gov (United States)

    Fleischmann, Achim; Thalmann, George N; Perren, Aurel; Seiler, Roland

    2014-03-01

    Histopathologic tumor regression grades (TRGs) after neoadjuvant chemotherapy predict survival in different cancers. In bladder cancer, corresponding studies have not been conducted. Fifty-six patients with advanced invasive urothelial bladder cancer received neoadjuvant chemotherapy before cystectomy and lymphadenectomy. TRGs were defined as follows: TRG1: complete tumor regression; TRG2: >50% tumor regression; TRG3: 50% or less tumor regression. Separate TRGs were assigned for primary tumors and corresponding lymph nodes. The prognostic impact of these 2 TRGs, the highest (dominant) TRG per patient, and competing tumor features reflecting tumor regression (ypT/ypN stage, maximum diameter of the residual tumor) were determined. Tumor characteristics in initial transurethral resection of the bladder specimens were tested for response prediction. The frequency of TRGs 1, 2, and 3 in the primary tumors were n=16, n=19, and n=21; corresponding data from the lymph nodes were n=31, n=9, and n=16. Interobserver agreement in determination of the TRG was strong (κ=0.8). Univariately, all evaluated parameters were significantly (P ≤ 0.001) related to overall survival; however, the segregation of the Kaplan-Meier curves was best for the dominant TRG. In multivariate analysis, only dominant TRG predicted overall survival independently (P=0.035). In transurethral resection specimens of the chemotherapy-naive bladder cancer, the only tumor feature with significant (Ptumor regression, the dominant TRG was the only independent risk factor. A favorable chemotherapy response is associated with a high proliferation rate in the initial chemotherapy-naive bladder cancer. This feature might help personalize neoadjuvant chemotherapy.

  15. Clinical and pathological implications of miRNA in bladder cancer

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    Braicu C

    2015-01-01

    important practical applications, taking into account that they modulate essential biological processes such as epithelial to mesenchymal transition, which is a mechanism relevant in bladder cancer. miRNAs collected from biological specimens can furnish valuable evidence with regard to bladder cancer oncogenesis, as they also have been linked to clinical outcomes in urothelial carcinoma. Therefore, a single miRNA or a signature of multiple miRNAs may improve risk stratification of patients and may supplement the histological diagnosis of urological tumors, particularly for bladder cancer.Keywords: bladder cancer, miRNA, prognostic, diagnostic

  16. Identification of Differently Expressed Genes in Chemical Carcinogen-induced Rat Bladder Cancers

    Institute of Scientific and Technical Information of China (English)

    Guangfu CHEN; Franky L. CHAN; Xu ZHANG; Peter S.F. CHAN

    2009-01-01

    Possible altered gene expression patterns in bladder turnout carcinogenesis in rat bladder cancers induced by BBN [N-butyl-N-(4-hydroxybutyl)nitrosamine] was examined by cDNA microarray analysis of gene expression profiles.Thirty Sprague-Dawley rats were given drinking water containing 0.05% BBN ad libitum for 24 to 28-weeks.Equal numbers of control rats were given tap water without BBN.After treatment,the rat bladders were excised for RNA extraction and histopathological examinations.Total RNAs were extracted from rat transitional cell carcinoma (TCC) tissues and micro-dissected normal rat bladder epithelia.The atlas glass rat microarray was used,which included oligonucleotides of 1081 rat genes.Some of the up-regulated genes in rat bladder TCCs were further confirmed by Northern blotting.Our results showed that the transcriptions of 30 genes were significantly elevated in the rat bladder TCCs,and these included fly proto-oncogene,Lipocortin 2,COX Ⅳ,COX Ⅴ a,and cathepsin D.Also,15 genes were significantly down-regulated in the rat bladder TCCs and they included B7.1,TNFrl,APOAI and VHL.The resuits of cDNA microarray analysis demonstrated that normal rat bladder epithelia and bladder TCC exhibited different and specific gene statement profiles.The increased expressions of the identified genes may play an important role in the chemically induced bladder carcinogenesis.

  17. Significance of ERBB2 Overexpression in Therapeutic Resistance and Cancer-Specific Survival in Muscle-Invasive Bladder Cancer Patients Treated With Chemoradiation-Based Selective Bladder-Sparing Approach

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Masaharu [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Koga, Fumitaka, E-mail: f-koga@cick.jp [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Yoshida, Soichiro [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Tamura, Tomoki [Department of Pathology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Fujii, Yasuhisa [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Ito, Eisaku [Department of Pathology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Kihara, Kazunori [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan)

    2014-10-01

    Purpose: To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. Methods and Materials: From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. Results: CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). Conclusions: ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder

  18. Kaempferol suppresses bladder cancer tumor growth by inhibiting cell proliferation and inducing apoptosis.

    Science.gov (United States)

    Dang, Qiang; Song, Wenbin; Xu, Defeng; Ma, Yanmin; Li, Feng; Zeng, Jin; Zhu, Guodong; Wang, Xinyang; Chang, Luke S; He, Dalin; Li, Lei

    2015-09-01

    The effects of the flavonoid compound, kaempferol, which is an inhibitor of cancer cell proliferation and an inducer of cell apoptosis have been shown in various cancers, including lung, pancreatic, and ovarian, but its effect has never been studied in bladder cancer. Here, we investigated the effects of kaempferol on bladder cancer using multiple in vitro cell lines and in vivo mice studies. The MTT assay results on various bladder cancer cell lines showed that kaempferol enhanced bladder cancer cell cytotoxicity. In contrast, when analyzed by the flow cytometric analysis, DNA ladder experiment, and TUNEL assay, kaempferol significantly was shown to induce apoptosis and cell cycle arrest. These in vitro results were confirmed in in vivo mice studies using subcutaneous xenografted mouse models. Consistent with the in vitro results, we found that treating mice with kaempferol significant suppression in tumor growth compared to the control group mice. Tumor tissue staining results showed decreased expressions of the growth related markers, yet increased expressions in apoptosis markers in the kaempferol treated group mice tissues compared to the control group mice. In addition, our in vitro and in vivo data showed kaempferol can also inhibit bladder cancer invasion and metastasis. Further mechanism dissection studies showed that significant down-regulation of the c-Met/p38 signaling pathway is responsible for the kaempferol mediated cell proliferation inhibition. All these findings suggest kaempferol might be an effective and novel chemotherapeutic drug to apply for the future therapeutic agent to combat bladder cancer.

  19. Early effects of preoperative radiation therapy for invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Isaka, Shigeo; Igarashi, Tatsuo; Ito, Haruo

    1983-10-01

    22 patients with high grade invasive bladder cancer were treated with preoperative radiation therapy (910 rad by fast neutron or 3000 rad by X ray during 2 weeks) followed by radical cystectomy and urinary diversion. 62.5 % of patients showed reduction in tumor size more than 50% evaluated by cystogram. Stage down was observed in 38% of patients compared between clinical and pathological stage. Histopathological effect of GII or GIII, according to the criteria described by Ohboshi, was noticed in 79 % of the patients. Better effect seemed to be obtained in fast neutron treated group than in X ray group. 19 patients received curative surgery, and 18 patients were alive without recurrence after 10 months (mean observed term). One died from lung metastasis 4.5 months after surgery. 50% of the patients complained of side effects of irradiation although they were tolerable, and 32% of the patients had major complications of surgery.

  20. Therapeutic potential of thalidomide for gemcitabine-resistant bladder cancer.

    Science.gov (United States)

    Huang, Yen Ta; Cheng, Chuan Chu; Chiu, Ted H; Lai, Pei Chun

    2015-11-01

    Controversial effects of thalidomide for solid malignancies have been reported. In the present study, we evaluate the effects of thalidomide for transitional cell carcinoma (TCC), the most common type of bladder cancer. Thalidomide precipitates were observed when its DMSO solution was added to the culture medium. No precipitation was found when thalidomide was dissolved in 45% γ-cyclodextrin, and this concentration of γ-cyclodextrin elicited slight cytotoxicity on TCC BFTC905 and primary human urothelial cells. Thalidomide-γ-cyclodextrin complex exerted a concentration-dependent cytotoxicity in TCC cells, but was relatively less cytotoxic (with IC50 of 200 µM) in BFTC905 cells than the other 3 TCC cell lines, possibly due to upregulation of Bcl-xL and HIF-1α mediated carbonic anhydrase IX, and promotion of quiescence. Gemcitabine-resistant BFTC905 cells were chosen for additional experiments. Thalidomide induced apoptosis through downregulation of survivin and securin. The secretion of VEGF and TNF-α was ameliorated by thalidomide, but they did not affect cell proliferation. Immune-modulating lenalidomide and pomalidomide did not elicit cytotoxicity. In addition, cereblon did not play a role in the thalidomide effect. Oxidative DNA damage was triggered by thalidomide, and anti-oxidants reversed the effect. Thalidomide also inhibited TNF-α induced invasion through inhibition of NF-κB, and downregulation of effectors, ICAM-1 and MMP-9. Thalidomide inhibited the growth of BFTC905 xenograft tumors in SCID mice via induction of DNA damage and suppression of angiogenesis. Higher average body weight, indicating less chachexia, was observed in thalidomide treated group. Sedative effect was observed within one-week of treatment. These pre-clinical results suggest therapeutic potential of thalidomide for gemcitabine-resistant bladder cancer.

  1. Body Mass Index and Bladder Cancer Risk: A Popu-lation-based Case-control Study in Shanghai%成年期体质指数与膀胱癌关系的全人群病例对照研究

    Institute of Scientific and Technical Information of China (English)

    张薇; 项永兵; 方茹蓉; 程家蓉; 袁剑敏; 高玉堂

    2011-01-01

    [Purpose] To evaluate the association between body mass index (BMI) at different ages in adulthood and risk of bladder cancer in Shanghai. [ Methods] A population-based case-control study was conducted in Shanghai during January 1996 to December 1998. The study included 608 incident cases of bladder cancer and 607 age- and sex-frequency matched population controls. Unconditional logistic regression models were used to estimate the odds ratios (Ors) and 95% confidence intervals (95% Cis) between BMI and bladder cancer risk with adjustment for age,smoking status,history of high risk occupation,history of bladder infections and other confounding factors. [Results] Increased BMI at age 20 was associated with an increased risk of bladder cancer among men. Subjects in the 2nd,3rd,and 4th quartiles of BMI had Ors (95% Cis) of 1.51 (95% Cl: 1.01-2.25),2.24 (95% Cl: 1.52-3.31) and 1.80 (95% Cl: 1.20-2.69), respectively, as compared with those in the lowest quartile of BMI (P-value for trend = 0.001). However.no statistically significant trends were observed for the association between highest BMI over lifetime or BMI at 10 years before reference year and bladder cancer risk. Adulthood BMIs also were associated with an increased risk of bladder cancer for women. Ors (95% Cis) of bladder cancer for women in the highest quartile of the highest BMI over lifetime, age 20 or 10 years prior to reference date were 2.23 (95% Cl: 1.08-4.60),3.27 (95%CI:1.52~ 7.03),and 3.63 (95% Cl:1.68-7.85),respectively,compared with the lowest quartile of respective BMIs (all P-values for trend<0.05). [Conclusions] BMI in early adult life for men and overall adulthood for women may be associated with the increased risk of bladder cancer.%[目的]研究成年期体质指数(BMI)与上海市区居民膀胱癌危险性的关系.[方法]采用全人群病例对照研究,共调查1996年1月1日~1998年12月31日期间诊断的上海市区膀胱癌新发病例608例,以及性别、年

  2. Attenuated XPC expression is not associated with impaired DNA repair in bladder cancer.

    Directory of Open Access Journals (Sweden)

    Kishan A T Naipal

    Full Text Available Bladder cancer has a high incidence with significant morbidity and mortality. Attenuated expression of the DNA damage response protein Xeroderma Pigmentosum complementation group C (XPC has been described in bladder cancer. XPC plays an essential role as the main initiator and damage-detector in global genome nucleotide excision repair (NER of UV-induced lesions, bulky DNA adducts and intrastrand crosslinks, such as those made by the chemotherapeutic agent Cisplatin. Hence, XPC protein might be an informative biomarker to guide personalized therapy strategies in a subset of bladder cancer cases. Therefore, we measured the XPC protein expression level and functional NER activity of 36 bladder tumors in a standardized manner. We optimized conditions for dissociation and in vitro culture of primary bladder cancer cells and confirmed attenuated XPC expression in approximately 40% of the tumors. However, NER activity was similar to co-cultured wild type cells in all but one of 36 bladder tumors. We conclude, that (i functional NER deficiency is a relatively rare phenomenon in bladder cancer and (ii XPC protein levels are not useful as biomarker for NER activity in these tumors.

  3. Bladder Stones

    Science.gov (United States)

    ... does not include routine preventive screening for bladder cancer.If you do not treat bladder stones, you can have lasting damage. This includes repeat UTIs or injury to your bladder, kidney, or urethra. Questions to ask your doctor How do I ...

  4. Mortality due to lung, laryngeal and bladder cancer in towns lying in the vicinity of combustion installations

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Perez, Javier [Environmental and Cancer Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, C/Sinesio Delgado, 6, 28029 Madrid (Spain); CIBER en Epidemiologia y Salud Publica (CIBERESP) (Spain)], E-mail: jgarcia@isciii.es; Pollan, Marina; Boldo, Elena; Perez-Gomez, Beatriz; Aragones, Nuria; Lope, Virginia; Ramis, Rebeca; Vidal, Enrique; Lopez-Abente, Gonzalo [Environmental and Cancer Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, C/Sinesio Delgado, 6, 28029 Madrid (Spain); CIBER en Epidemiologia y Salud Publica (CIBERESP) (Spain)

    2009-04-01

    Background: Installations that burn fossil fuels to generate power may represent a health problem due to the toxic substances which they release into the environment. Objectives: To investigate whether there might be excess mortality due to tumors of lung, larynx and bladder in the population residing near Spanish combustion installations included in the European Pollutant Emission Register. Methods: Ecologic study designed to model sex-specific standardized mortality ratios for the above three tumors in Spanish towns, over the period 1994-2003. Population exposure to pollution was estimated on the basis of distance from town of residence to pollution source. Using mixed Poisson regression models, we analyzed: risk of dying from cancer in a 5-kilometer zone around installations that commenced operations before 1990; effect of type of fuel used; and risk gradient within a 50-kilometer radius of such installations. Results: Excess mortality (relative risk, 95% confidence interval) was detected in the vicinity of pre-1990 installations for lung cancer (1.066, 1.041-1.091 in the overall population; 1.084, 1.057-1.111 in men), and laryngeal cancer among men (1.067, 0.992-1.148). Lung cancer displayed excess mortality for all types of fuel used, whereas in laryngeal and bladder cancer, the excess was associated with coal-fired industries. There was a risk gradient effect in the proximity of a number of installations. Conclusions: Our results could support the hypothesis of an association between risk of lung, laryngeal and bladder cancer mortality and proximity to Spanish combustion installations.

  5. Reduced LAK cytotoxicity of peripheral blood mononuclear cells in patients with bladder cancer

    DEFF Research Database (Denmark)

    Hermann, G G; Petersen, K R; Steven, K

    1990-01-01

    The cytotoxicity of unstimulated peripheral blood mononuclear cells (US-PBMC), phytohemagglutinin (PHA)-stimulated PBMC (PS-PBMC) and interleukin-2 (IL-2)-activated PBMC (LAK cells) was assessed in patients with noninvasive and invasive transitional-cell bladder cancer and compared with those...... determined in healthy controls. The differences in the cytotoxicities were correlated with specific changes in the subsets of peripheral blood mononuclear cells (PBMC). PBMC from 37 patients and 13 healthy controls were tested against the bladder cancer cell line T24 in 51Cr-release assays. The PBMC subsets...... that the reduced ability of bladder cancer patient PBMC to develop LAK-cell cytotoxicity is a result of a low incidence of CD56+ and CD57+ cells in the blood. These findings indicate that IL-2 therapy alone might not be a sufficient therapy of bladder cancer patients....

  6. Nanotechnology in bladder cancer: current state of development and clinical practice.

    Science.gov (United States)

    Tomlinson, Ben; Lin, Tzu-yin; Dall'Era, Marc; Pan, Chong-Xian

    2015-01-01

    Nanotechnology is being developed for the diagnosis and treatment of both nonmyoinvasive bladder cancer (NMIBC) and invasive bladder cancer. The diagnostic applications of nanotechnology in NMIBC mainly focus on tumor identification during endoscopy to increase complete resection of bladder cancer while nanotechnology to capture malignant cells or their components continues to be developed. The therapeutic applications of nanotechnology in NMIBC are to reformulate biological and cytotoxic agents for intravesical instillation, combine both diagnostic and therapeutic application in one nanoformulation. In invasive and advanced bladder cancer, magnetic resonance imaging with supraparamagnetic iron oxide nanoparticles can improve the sensitivity and specificity in detecting small metastasis to lymph nodes. Nanoformulation of cytotoxic agents can potentially decrease the toxicity while increasing efficacy.

  7. Parthenolide Induces Apoptosis and Cell Cycle Arrest of Human 5637 Bladder Cancer Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Guang Cheng

    2011-08-01

    Full Text Available Parthenolide, the principal component of sesquiterpene lactones present in medical plants such as feverfew (Tanacetum parthenium, has been reported to have anti-tumor activity. In this study, we evaluated the therapeutic potential of parthenolide against bladder cancer and its mechanism of action. Treatment of bladder cancer cells with parthenolide resulted in a significant decrease in cell viability. Parthenolide induced apoptosis through the modulation of Bcl-2 family proteins and poly (ADP-ribose polymerase degradation. Treatment with parthenolide led to G1 phase cell cycle arrest in 5637 cells by modulation of cyclin D1 and phosphorylated cyclin-dependent kinase 2. Parthenolide also inhibited the invasive ability of bladder cancer cells. These findings suggest that parthenolide could be a novel therapeutic agent for treatment of bladder cancer.

  8. Cases of a Borderline Pathology That Can Mimic Bladder Cancer: Primary Amyloidosis of Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Cemal Selçuk İşoğlu

    2015-06-01

    Full Text Available Amyloidosis is a disease characterised by accumulation of a fibrillar protein called amyloid in the extracellular space. The kidneys, ureters and the bladder can be affected in the urinary tract. However, primary amyloidosis of bladder is a rare entity. Macroscopic hematuria could be the first and only symptom of primary amyloidosis of the bladder; therefore, it has similar findings with urinary tract malignancies. Histopathological evaluation is mandatory for the diagnosis. Follow-up should always include cystoscopic evaluation as recurrence is expected in the natural course.

  9. Anterior urethra sparing cystoprostatectomy for bladder cancer: a 10-year, single center experience

    OpenAIRE

    Hayakawa, Nozomi; Kikuno, Nobuyuki; Ishihara, Hiroki; Ryoji, Osamu; Tanabe, Kazunari

    2015-01-01

    Purpose Decision making regarding the urethra before and after radical cystectomy due to urothelial carcinoma has always been controversial. To determine whether anterior urethra sparing cystoprostatectomy for bladder cancer is an oncologically-safe procedure, we evaluated the long-term oncologic clinical outcome. Patients and methods A total of 51 male patients with cTa-4N0-2M0 bladder cancer were treated with anterior urethra sparing cystoprostatectomy and simultaneous urinary diversion bet...

  10. Intervention of nicotine on MNU-induced bladder cancer in rats.

    Science.gov (United States)

    Liu, Di; Pan, Feng; Li, Bing; Han, Xiaomin; Li, Wencheng; Shi, Ying; Pang, Zili; Zhang, Qijun

    2011-02-01

    This study examined the effect of nicotine on the expression of mutant p53 (mt-p53) in bladder cancer rats. The rat models of bladder cancer were established by infusing N-methyl-nitroso-urea (MNU, 10 mg/kg every 2 weeks for 8 weeks) into the bladder. Pathological examination on the bladder was conducted to confirm the establishment of the model. All the bladder cancer rats were randomly divided into an MNU group and 3 nicotine groups. In the nicotine groups, the rats were intragastrically administered nicotine at different concentrations (25, 15, 5 mg/kg respectively) 3 times per week for 8 weeks. The mt-p53 expression was detected by the immunohistochemical method. The results showed that rat bladder cancer models developed histopathological changes of bladder transitional cell carcinoma. The positive rate of mt-p53 expression in the 3 nicotine groups (25, 15, 5 mg/kg) was 75.00%, 58.33% and 41.67% by the 14th week, respectively, significantly higher than that in the MNU group (33.33%) (all Pcancer partially by increasing the expression of mt-p53.

  11. CXCL5 knockdown expression inhibits human bladder cancer T24 cells proliferation and migration

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jiajia [Department of Laboratory Medicine, Peking University Third Hospital, Beijing (China); Zhu, Xi [Department of Urology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing (China); Zhang, Jie, E-mail: zhangjiebjmu@163.com [Department of Laboratory Medicine, Peking University Third Hospital, Beijing (China)

    2014-03-28

    Highlights: • We first demonstrated CXCL5 is highly expressed in human bladder tumor tissues and cells. • CXCL5 knockdown inhibits proliferation, migration and promotes apoptosis in T24 cells. • CXCL5 knockdown inhibits Snail, PI3K-AKT and ERK1/2 signaling pathways in T24 cells. • CXCL5 is critical for bladder tumor growth and progression. - Abstract: CXCL5 (epithelial neutrophil activating peptide-78) which acts as a potent chemoattractant and activator of neutrophil function was reported to play a multifaceted role in tumorigenesis. To investigate the role of CXCL5 in bladder cancer progression, we examined the CXCL5 expression in bladder cancer tissues by real-time PCR and Western blot, additionally, we used shRNA-mediated silencing to generate stable CXCL5 silenced bladder cancer T24 cells and defined its biological functions. Our results demonstrated that mRNA and protein of CXCL5 is increased in human bladder tumor tissues and cell lines, down-regulation of CXCL5 in T24 cells resulted in significantly decreased cell proliferation, migration and increased cell apoptosis in vitro through Snail, PI3K-AKT and ERK1/2 signaling pathways. These data suggest that CXCL5 is critical for bladder tumor growth and progression, it may represent a potential application in cancer diagnosis and therapy.

  12. The Investigation Image-guided Radiation Therapy of Bladder Cancer Patients

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    Bae, Seong Soo; Bae, Sun Myung; Kim, Jin San; Kang, Tae Young; Back, Geum Mun; Kwon, Kyung Tae [Dept. of Radiation Oncology, Asan Medical Center, Seoul (Korea, Republic of)

    2012-03-15

    In hospital image-guided radiation therapy in patients with bladder cancer to enhance the reproducibility of the appropriate amount, depending on the patient's condition, and image-guided injection of saline system (On-Board Imager system, OBI, VARIAN, USA) three of the Cone-Beam CT dimensional matching (3D-3D matching) to be the treatment. In this study, the treatment of patients with bladder cancer at Cone-Beam CT image obtained through the analysis of the bones based matching and matching based on the bladder to learn about the differences, the bladder's volume change injected saline solution by looking at the bladder for the treatment of patients with a more appropriate image matching is to assess how the discussion. At our hospital from January 2009 to April 2010 admitted for radiation therapy patients, 7 patients with bladder cancer using a Folly catheter of residual urine in the bladder after removing the amount determined according to individual patient enough to inject saline CT-Sim was designed after the treatment plan. After that, using OBI before treatment to confirm position with Cone-Beam CT scan was physician in charge of matching was performed in all patients. CBCT images using a total of 45 bones, bladder, based on image matching and image matching based on the difference were analyzed. In addition, changes in bladder volume of Eclipse (version 8.0, VARIAN, USA) persuaded through. Bones, one based image matching based on the bladder and re-matching the X axis is the difference between the average 3{+-}2 mm, Y axis, 1.8{+-}1.3 mm, Z-axis travel distance is 2.3{+-}1.7 mm and the overall 4.8{+-}2.0 mm, respectively. The volume of the bladder compared to the baseline showed a difference of 4.03{+-}3.97%. Anatomical location and nature of the bladder due to internal movement of the bones, even after matching with the image of the bladder occurred in different locations. In addition, the volume of saline-filled bladder showed up the difference

  13. DDX39 acts as a suppressor of invasion for bladder cancer.

    Science.gov (United States)

    Kato, Minoru; Wei, Min; Yamano, Shotaro; Kakehashi, Anna; Tamada, Satoshi; Nakatani, Tatsuya; Wanibuchi, Hideki

    2012-07-01

    The object of the present study was to identify markers for predicting urinary bladder cancer progression by comparative proteome analysis of bladder cancers and paired normal mucosas. We found that DDX39 was overexpressed in four of six bladder cancers examined compared with respective control tissues. Immunohistochemical analysis using 303 bladder cancer specimens revealed that DDX39 was inversely correlated to pT stage and histological grade progression. The incidence of DDX39(high) tumors (positive cells ≥50%) was 68.6%, 43.5%, 20.0%, and 5.3% in pTa, pT1, pTis, and ≥pT2 tumors, respectively, and 65.2%, 60.7%, and 19.6% in G1, G2, and G3 tumors, respectively. The incidence of DDX39(high) tumors was significantly lower in pT1 and ≥pT2 compared to pTa tumors, and also significantly lower in G3 compared to G1 and G2 tumors. Follow-up analysis (n = 105) revealed that DDX39(low) tumors (positive cells <50%) were associated with disease progression (hazard ratio 7.485; P = 0.0083). Furthermore, DDX39-knockdown bladder cancer cells increased their invasion ability compared to negative control cells. These results suggest that DDX39 is a suppressor of invasion and loss of its function predicts disease progression in bladder cancers.

  14. Induction of G1 cell cycle arrest and apoptosis by berberine in bladder cancer cells.

    Science.gov (United States)

    Yan, Keqiang; Zhang, Cheng; Feng, Jinbo; Hou, Lifang; Yan, Lei; Zhou, Zunlin; Liu, Zhaoxu; Liu, Cheng; Fan, Yidon; Zheng, Baozhong; Xu, Zhonghua

    2011-07-01

    Bladder cancer is the ninth most common type of cancer, and its surgery is always followed by chemotherapy to prevent recurrence. Berberine is non-toxic to normal cells but has anti-cancer effects in many cancer cell lines. This study was aimed to determine whether berberine inhibits the cell proliferation and induces cell cycle arrest and apoptosis in BIU-87 and T24 bladder cancer cell line. The superficial bladder cancer cell line BIU-87 and invasive T24 bladder cancer cells were treated with different concentrations of berberine. MTT assay was used to determine the effects of berberine on the viability of these cells. The cell cycle arrest was detected through propidium iodide (PI) staining. The induction of apoptosis was determined through Annexin V-conjugated Alexa Fluor 488 (Alexa488) staining. Berberine inhibited the viability of BIU-87 and T24 cells in a dose- and time-dependent manner. It also promoted cell cycle arrest at G0/G1 in a dose-dependent manner and induced apoptosis. We observed that H-Ras and c-fos mRNA and protein expressionswere dose-dependently and time-dependently decreased by berberine treatment. Also, we investigated the cleaved caspase-3 and caspase-9 protein expressions increased in a dose-dependent manner. Berberine inhibits the cell proliferation and induces cell cycle arrest and apoptosis in BIU-87, bladder cancer cell line and T24, invasive bladder cancer cell line. Berberine can inhibit the oncogentic H-Ras and c-fos in T24 cells, and can induce the activation of the caspase-3 and caspase-9 apoptosis. Therefore, berberine has the potential to be a novel chemotherapy drug to treat the bladder cancer by suppressing tumor growth.

  15. Metastatic Bladder Cancer Presenting with Persistent Hematuria in Young Man with Cystic Fibrosis

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    Premal Patel

    2013-01-01

    Full Text Available We report a case of metastatic bladder cancer developing in a young man with cystic fibrosis (CF that was initially diagnosed as ureterolithiasis and managed as renal colic. With the improved survival of patients with CF, an increasing burden of extrapulmonary disease manifestations is apparent. Renal colic is observed at an increased frequency in patients with CF relative to the general population and is a commonly recognized cause of hematuria. However, CF patients harboring a malignancy are recognized to be at increased risk of delayed identification owing to atypical symptoms and lack of demographic risk factors. This case illustrates how investigations to rule out malignancy are warranted in those CF patients not responding to therapies directed towards presumptive diagnoses.

  16. Metastatic bladder cancer presenting with persistent hematuria in young man with cystic fibrosis.

    Science.gov (United States)

    Patel, Premal; Rabin, Harvey R; Vickers, Michael M; Parkins, Michael D

    2013-01-01

    We report a case of metastatic bladder cancer developing in a young man with cystic fibrosis (CF) that was initially diagnosed as ureterolithiasis and managed as renal colic. With the improved survival of patients with CF, an increasing burden of extrapulmonary disease manifestations is apparent. Renal colic is observed at an increased frequency in patients with CF relative to the general population and is a commonly recognized cause of hematuria. However, CF patients harboring a malignancy are recognized to be at increased risk of delayed identification owing to atypical symptoms and lack of demographic risk factors. This case illustrates how investigations to rule out malignancy are warranted in those CF patients not responding to therapies directed towards presumptive diagnoses.

  17. Homing peptide guiding optical molecular imaging for the diagnosis of bladder cancer

    Science.gov (United States)

    Yang, Xiao-feng; Pang, Jian-zhi; Liu, Jie-hao; Zhao, Yang; Jia, Xing-you; Li, Jun; Liu, Reng-xin; Wang, Wei; Fan, Zhen-wei; Zhang, Zi-qiang; Yan, San-hua; Luo, Jun-qian; Zhang, Xiao-lei

    2014-11-01

    Background: The limitations of primary transurethral resection of bladder tumor (TURBt) have led the residual tumors rates as high as 75%. The intraoperative fluorescence imaging offers a great potential for improving TURBt have been confirmed. So we aim to distinguish the residual tumors and normal mucosa using fluorescence molecular imaging formed by conjugated molecule of the CSNRDARRC bladder cancer homing peptide with fluorescent dye. The conjugated molecule was abbreviated FIuo-ACP. In our study, we will research the image features of FIuo-ACP probe targeted bladder cancer for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo. Methods: After the FIuo-ACP probe was synthetized, the binding sites, factors affecting binding rates, the specificity and the targeting of Fluo-ACP labeled with bladder cancer cells were studied respectively by laser scanning confocal microscope (LSCM), immunofluorescence and multispectral fluorescence ex vivo optical molecular imaging system. Results: The binding sites were located in nucleus and the binding rates were correlated linearly with the dose of probe and the grade of pathology. Moreover, the probe has a binding specificity with bladder cancer in vivo and ex vivo. Tumor cells being labeled by the Fluo-ACP, bright green spots were observed under LSCM. The tissue samples and tumor cells can be labeled and identified by fluorescence microscope. Optical molecular imaging of xenograft tumor tissues was exhibited as fluorescent spots under EMCCD. Conclusion: The CSNRDARRC peptides might be a useful bladder cancer targeting vector. The FIuo-ACP molecular probe was suitable for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo.

  18. Urinary APE1/Ref-1: A Potential Bladder Cancer Biomarker.

    Science.gov (United States)

    Choi, Sunga; Shin, Ju Hyun; Lee, Yu Ran; Joo, Hee Kyoung; Song, Ki Hak; Na, Yong Gil; Chang, Seok Jong; Lim, Jae Sung; Jeon, Byeong Hwa

    2016-01-01

    Bladder cancer (BCa) is one of the most common urothelial cancers with still noticeable incidence rate. Early detection of BCa is highly correlated with successful therapeutic outcomes. We previously showed that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) was expressed at an increased level in the serum of BCa patients when compared to the level in healthy controls. In this study, we investigated whether urinary APE1/Ref-1 was also elevated in patients with BCa. In this case-control study, voided urine was collected from 277 subjects including 169 BCa patients and 108 non-BCa controls. Urinary APE1/Ref-1 level was assessed by enzyme-linked immunosorbent assay (ELISA). APE1/Ref-1 levels were significantly elevated in BCa patients relative to levels in non-BCa controls and were correlated with tumor grade and stage. Urinary APE1/Ref-1 levels were also higher in patients with recurrence history of BCa. The receiver operating characteristics (ROC) curve of APE1/Ref-1 showed an area under the curve of 0.83, indicating the reliability and validity of this biomarker. The optimal combination of sensitivity and specificity was determined to be 82% and 80% at a cut-off value of 0.376 ng/100 μL for detection of APE1/Ref-1 in urine. In conclusion, urinary APE1/Ref-1 levels measured from noninvasively obtained body fluids would be clinically applicable for diagnosis of BCa.

  19. Expression and significance of B7-H1 in peripheral blood dendritic cells from patients with bladder cancer

    Institute of Scientific and Technical Information of China (English)

    Chuanbiao Ji; Yonghua Wang; Qinchao Yu; Jing Liu; Yanan Liu; Jie Cui

    2013-01-01

    Objective: The aim of this study was to study the expression and the clinical significance of B7-H1 on dendritic cells (DCs) in peripheral blood from patients with bladder cancer. Methods: Peripheral blood mononuclear cell were disparted from 30 bladder cancer patients and 7 healthy controls by density gradient centrifugation and then co-cultured. The expression of B7-H1 on DCs were analyzed by flow cytometry. Results: Expression of B7-H1 on DCs in bladder cancer was higher than healthy controls (P < 0.01). And the expression were strongly associated with the pathological grade and clinical stage of bladder cancer (P < 0.05). Conclusion: The up-regulation of B7-H1 on DCs was strongly associated with neoplastic progression of bladder cancer. B7-H1/programmed death (PD)-1 signal pathway may also play an important role in immune escape of bladder cancer during initial phase of T cell immune response.

  20. Optical spectroscopy by 5-aminolevulinic acid hexylester induced photodynamic treatment in rat bladder cancer

    Science.gov (United States)

    Larsen, Eivind L. P.; Randeberg, Lise L.; Gederaas, Odrun A.; Arum, Carl-Jørgen; Krokan, Hans E.; Hjelme, Dag R.; Svaasand, Lars O.

    2006-02-01

    Photodynamic therapy (PDT) is a treatment modality which has been shown to be effective for both malignant and non-malignant diseases. New photosensitizers such as 5-aminolevulinic acid hexylester (hALA) may increase the efficiency of PDT. Monitoring of the tissue response provides important information for optimizing factors such as drug and light dose for this treatment modality. Optical spectroscopy may be suited for this task. To test the efficacy of hALA induced PDT, a study on rats with a superficial bladder cancer model, in which a bladder cancer cell line (AY-27) is instilled, will be performed. Preliminary studies have included a PDT feasibility study on rats, fluorescence spectroscopy on AY-27 cell suspensions, and optical reflection and fluorescence spectroscopy in rat bladders in vivo. The results from the preliminary studies are promising, and the study on hALA induced PDT treatment of bladder cancer will be continued.

  1. Frequencies of poor metabolizers of cytochrome P450 2C19 in esophagus cancer, stomach cancer, lung cancer and bladder cancer in Chinese population

    Institute of Scientific and Technical Information of China (English)

    Wei-Xing Shi; Shu-Qing Chen

    2004-01-01

    AIM: To investigate the association between cytochrome P450 2C19 (CYP2C19) gene polymorphism and cancer susceptibility by genotyping of CYP2C19 poor metabolizers (PMs) in cancer patients.METHODS: One hundred and thirty-five cases of esophagus cancer, 148 cases of stomach cancer, 212 cases of lung cancer, 112 cases of bladder cancer and 372 controls were genotyped by allele specific amplification-polymerase chain reaction (ASA-PCR) for CYP2C19 PMs. The frequencies of PMs in cancer groups and control group were compared.RESULTS: The frequencies of PMs of CYP2C19 were 34.1%(46/135) in the group of esophagus cancer patients, 31.8%(47/148) in the stomach cancer patients, 34.4%(73/212) in the group of lung cancer patients, only 4.5% (5/112) in the bladder cancer patients and 14.0%(52/372) in control group.There were statistical differences between the cancer groups and control group (esophagus cancer, x2=25.65, P<0.005,OR=3.18, 95% CI=2.005-5.042; stomach cancer, x2=21.70,P<0.005, OR=2.86, 95%CI=1.820-4.501; lung cancer,x2=33.58, P<0.005, OR=3.23, 95%CI=1.503-6.906; bladder cancer, x2=7.50, P<0.01, OR=0.288, 95%CI=0.112-0.740).CONCLUSION: CYP2C19 PMs have a high incidence of esophagus cancer, stomach cancer and lung cancer, conversely they have a low incidence of bladder cancer. It suggests that CYP2C19 may participate in the activation of procarcinogen of esophagus cancer, stomach cancer and lung cancer, but may involve in the detoxification of carcinogens of bladder cancer.

  2. Polymorphism of N-acetyltransferase 2 (NAT2) Gene Polymorphism in Shanghai population:Occupational and Non-occupational Bladder Cancer Patient Groups

    Institute of Scientific and Technical Information of China (English)

    QING-WEN MA; GUO-FANG LIN; JI-GANG CHEN; CUI-QING XIANG; WEI-CHAO GUO; KLAUS GOLKA; JIAN-HUA SHEN

    2004-01-01

    Arylamine N-acetyltransferases (NATs) are involved in the detoxification of aromatic amines and hydrazine. In order to explore the possible association of NAT2 polymorphism with bladder cancer risk in benzidine exposed or non-exposed Chinese individuals, healthy subjects, subjects with bladder cancer of a former benzidine exposed cohort in Shanghai dyestuff industry and a group of bladder cancer patients without known occupational exposure to aromatic amines were genotyped for NAT2 gene polymorphism. Methods NAT2 genotyping was performed with a set of RFLP procedures at seven major polymorphic loci of gene coding area: G191A, C282T, T341C, C481T, G590A, A803G and G857A. Results The wild allele NAT2 *4 was the most prevalent allele (59%) in healthy individuals. The alleles NAT2*6A and NAT2*7B were also frequently observed (21% and 17%, respectively). In contrast to Caucasians, the percentage of slow acetylators was lower (12% in Chinese vs. 58% in Caucasians, P<0.001). No relevant differences were observed for homogenous rapid, heterogeneous rapid/slow and homogeneous slow acetylation genotypes between the healthy subjects and both groups of bladder cancer patients. Conclusion The present work did not support the association of slow acetylating genotypes of NAT2 gene with elevated risk of bladder cancer in Chinese whereas it was documented as an important genetically determined risk factor in Caucasians. Different mechanisms might play a role in individual susceptibility to bladder cancer related with aromatic amine exposure in various races or ethnic groups.

  3. Re: Sequential Combination of Mitomycin C Plus Bacillus Calmette-Guerin (BCG Is More Effective but More Toxic Than BCG Alone in Patients with Non–Muscle-Invasive Bladder Cancer in Intermediate-and High-Risk Patients: Final Outcome of CUETO 93009, A Randomized Prospective Trial

    Directory of Open Access Journals (Sweden)

    Eduardo Solsona

    2015-03-01

    Full Text Available EAU Guideline recommendation in non-muscle invasive bladder cancer (NMIBC is that patients who have intermediate or high risk for recurrence and intermediate risk for progression should receive early single dose intravesical chemotherapy followed by maintenance or a minimum of 1 year of BCG. Intravesical Mitomycin C (MMC plus Bacillus Calmette-Guerin (BCG treatment schemes were studied. However, MMC+BCG were not found to be superior to BCG alone (1,2. In the present study, authors conducted a randomized prospective trial on combination of MMC+BCG (n=192 or BCG alone (n=190. EORTC definition of NMIBC intermediate and high-risk patientswere included in the study. Unlike previous reported studies, disease-free interval at 5 years for MMC+BCG was found to be significantly better (HR: 0.57; 95% CI, 0.39 -0,83; p=0.003 than BCG alone. In an interim analysis, excessive toxicity was observed in MMC+BCG than BCG alone group. Consequently MMC dose was reduced from 30 mg to 10 mg. However, toxicity remained higher in the MMC+BCG group. Especially in EORTC highrisk NMIBCs, MMC+BCG is better than BCG alone, but with worse toxicity. In conclusion, despite some limitations, the results of Solsona et al. provided a new potential bladder-sparing management alternative, but it has higher toxicity. Additional studies are required to confirm these findings and availability of a less toxic intravesical chemotherapeutic agent.

  4. Distinct SNP combinations confer susceptibility to urinary bladder cancer in smokers and non-smokers.

    Science.gov (United States)

    Schwender, Holger; Selinski, Silvia; Blaszkewicz, Meinolf; Marchan, Rosemarie; Ickstadt, Katja; Golka, Klaus; Hengstler, Jan G

    2012-01-01

    Recently, genome-wide association studies have identified and validated genetic variations associated with urinary bladder cancer (UBC). However, it is still unknown whether the high-risk alleles of several SNPs interact with one another, leading to an even higher disease risk. Additionally, there is no information available on how the UBC risk due to these SNPs compare to the risk of cigarette smoking and to occupational exposure to urinary bladder carcinogens, and whether the same or different SNP combinations are relevant in smokers and non-smokers. To address these questions, we analyzed the genotypes of six SNPs, previously found to be associated with UBC, together with the GSTM1 deletion, in 1,595 UBC cases and 1,760 controls, stratified for smoking habits. We identified the strongest interactions of different orders and tested the stability of their effect by bootstrapping. We found that different SNP combinations were relevant in smokers and non-smokers. In smokers, polymorphisms involved in detoxification of cigarette smoke carcinogens were most relevant (GSTM1, rs11892031), in contrast to those in non-smokers with MYC and APOBEC3A near polymorphisms (rs9642880, rs1014971) being the most influential. Stable combinations of up to three high-risk alleles resulted in higher odds ratios (OR) than the individual SNPs, although the interaction effect was less than additive. The highest stable combination effects resulted in an OR of about 2.0, which is still lower than the ORs of cigarette smoking (here, current smokers' OR: 3.28) and comparable to occupational carcinogen exposure risks which, depending on the workplace, show mostly ORs up to 2.0.

  5. Distinct SNP combinations confer susceptibility to urinary bladder cancer in smokers and non-smokers.

    Directory of Open Access Journals (Sweden)

    Holger Schwender

    Full Text Available Recently, genome-wide association studies have identified and validated genetic variations associated with urinary bladder cancer (UBC. However, it is still unknown whether the high-risk alleles of several SNPs interact with one another, leading to an even higher disease risk. Additionally, there is no information available on how the UBC risk due to these SNPs compare to the risk of cigarette smoking and to occupational exposure to urinary bladder carcinogens, and whether the same or different SNP combinations are relevant in smokers and non-smokers. To address these questions, we analyzed the genotypes of six SNPs, previously found to be associated with UBC, together with the GSTM1 deletion, in 1,595 UBC cases and 1,760 controls, stratified for smoking habits. We identified the strongest interactions of different orders and tested the stability of their effect by bootstrapping. We found that different SNP combinations were relevant in smokers and non-smokers. In smokers, polymorphisms involved in detoxification of cigarette smoke carcinogens were most relevant (GSTM1, rs11892031, in contrast to those in non-smokers with MYC and APOBEC3A near polymorphisms (rs9642880, rs1014971 being the most influential. Stable combinations of up to three high-risk alleles resulted in higher odds ratios (OR than the individual SNPs, although the interaction effect was less than additive. The highest stable combination effects resulted in an OR of about 2.0, which is still lower than the ORs of cigarette smoking (here, current smokers' OR: 3.28 and comparable to occupational carcinogen exposure risks which, depending on the workplace, show mostly ORs up to 2.0.

  6. Hair Dyes and Cancer Risk

    Science.gov (United States)

    ... dye use and bladder cancer: a meta-analysis. Annals of Epidemiology 2014; 24(2),151–159. [PubMed ... in a prospective cohort of Chinese women. Cancer Science 2009; 100(6):1088-1091. [PubMed Abstract] Related ...

  7. Genetic variants in urinary bladder cancer: collective power of the "wimp SNPs".

    Science.gov (United States)

    Golka, Klaus; Selinski, Silvia; Lehmann, Marie-Louise; Blaszkewicz, Meinolf; Marchan, Rosemarie; Ickstadt, Katja; Schwender, Holger; Bolt, Hermann M; Hengstler, Jan G

    2011-06-01

    In recent years, genome-wide association studies (GWAS) have identified more than 300 validated associations between genetic variants and risk of approximately 70 common diseases. A small number of rare variants with a frequency of usually less than 1% are associated with a strongly enhanced risk, such as genetic variants of TP53, RB1, BRCA1, and BRCA2. Only a very small number of SNPs (with a frequency of more that 1% of the rare allele) have effects of a factor of two or higher. Examples include APOE4 in Alzheimer's disease, LOXL1 in exfoliative glaucoma, and CFH in age-related macular degeneration. However, the majority of all identified SNPs have odds ratios between 1.1 and 1.5. In the case of urinary bladder cancer, all known SNPs that have been validated in sufficiently large populations are associated with odds ratios smaller than 1.5. These SNPs are located next to the following genes: MYC, TP63, PSCA, the TERT-CLPTM1L locus, FGFR3, TACC3, NAT2, CBX6, APOBEC3A, CCNE1, and UGT1A. It is likely that these moderate risk or "wimp SNPs" interact, and because of their high number, collectively have a strong influence on whether an individual will develop cancer or not. It should be considered that variants identified so far explain only approximately 5-10% of the overall inherited risk. Possibly, the remaining variance is due to an even higher number of SNPs with odds ratios smaller than 1.1. Recent studies have provided the following information: (1) The functions of genes identified as relevant for bladder cancer focus on detoxification of carcinogens, control of the cell cycle and apoptosis, as well as maintenance of DNA integrity. (2) Many novel SNPs are far away from the protein coding regions, suggesting that these SNPs are located on distant-acting transcriptional enhancers. (3) The low odds ratio of each individual bladder cancer-associated SNP is too low to justify reasonable preventive measures. However, if the recently identified SNPs interact, they may

  8. Combined intraarterial cisplatin infusion and radiation therapy for invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mizoguchi, Hiroaki; Nomura, Yoshio; Terada, Katsuhiko; Nakagawa, Masayuki; Ogata, Jiro [Oita Medical Univ., Hasama (Japan)

    1995-03-01

    Twenty-three patients with invasive bladder cancer (T2 in 17, T3 in 6) were treated initially with combined intraarterial cisplatin infusion and radiation therapy. Cisplatin (50 mg) was infused into the internal iliac artery through a subcutaneous reservoir twice a week over three weeks while concurrent radiation therapy with 30 Gy, delivered in 15 fractions, was given. In 23 patients, 6 received additional cisplatin infusion and the other 17 had transurethral resection of bladder tumor (TURBT). Two of the patients undergoing total cystectomy exhibited a complete response (CR). Thus overall response rate was 87% (CR in 13 and partial response in 7). CR was achieved in 53% for T2 patients and 67% for T3 patients. CR was slightly higher in patients with non-papillary cancer than those with papillary one. Toxic reaction included a decrease in bladder capacity in 2 patients and severe diarrhea due to methicillin-resistant Staphylococcus aureus colitis in one. The other toxicities, including nausea, vomiting, neurotoxicity and myelosuppression, were tolerable. All except for one are alive. Seven patients had a local recurrence of bladder cancer. One patient developed invasive bladder cancer reaching the prostatic urethra. One other patient had recurrence at the same site as the previous tumor. Five others had superficial bladder cancer and were managed by TURBT. Bladder function was preserved in 65% at a mean follow-up of 29 months. In conclusion, the combined intraarterial cisplatin infusion and radiation therapy is useful for the initial treatment of invasive bladder cancer. (N.K.).

  9. [Neoadjuvant chemotherapy of invasive cancer of the urinary bladder].

    Science.gov (United States)

    Selivanov, S P; Isaeva, S N; Kovalik, T A; Chén', M N; Aleksandrovich, I N; Kaliev, E A

    2007-01-01

    We studied efficacy of a combination of intraosseous and systemic administration of drugs in patients with invasive cancer of the urinary bladder (UB). A total of 20 patients aged 54-79 years with verified had recurrence, 2 had tumors with continuous growth. T2N0M0 UB carcinoma was diagnosed in 7 patients, T3N0M0--in 12, T6N0M0--in 1 patient. All the patients received systemic chemotherapy with gemzar in a single daily dose 800-1000 mg/m2 on day 1, 7 and 14. On day 2 a single intraosseous 100 mg eloxatin was given. A total of three courses of combined chemotherapy with 4-week interval was used. Intravenous gemzar administration was accompanied with mild leukopenia in 4 patients, moderate leukopenia--in 1, allergic reaction--in 2 patients. This required gemzar discontinuation. No side effects were seen in response to intraosseous administration of eloxatin. The combined chemotherapy produced complete regression of UB cancer in 3 of 18 patients, partial regression--in 12, stabilization--in 3 patients. Neither local nor long-term tumor progression was found. Short-term therapeutic efficacy of combined therapy was 70%. Fifteen patients with partial regression or stabilization have undergone transurethral resection. Duration of a recurrence-free period reached 5 to 72 months (mean 17 months). The neoadjuvant chemotherapy proposed by us allows achievement of a high percentage of regression in patients with invasive UB cancer located in UB cervix and provides concervative surgery including patients over 70 years of age.

  10. Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival

    Directory of Open Access Journals (Sweden)

    Hsieh Fu-Chuan

    2008-10-01

    Full Text Available Abstract Background Constitutive activation of signal transducer and activator of transcription 3 (Stat3 signaling pathway plays an important role in several human cancers. Activation of Stat3 is dependent on the phosphorylation at the tyrosine residue 705 by upstream kinases and subsequent nuclear translocation after dimerization. It remains unclear whether oncogenic Stat3 signaling pathway is involved in the oncogenesis of bladder cancer. Results We found that elevated Stat3 phosphorylation in 19 of 100 (19% bladder cancer tissues as well as bladder cancer cell lines, WH, UMUC-3 and 253J. To explore whether Stat3 activation is associated with cell growth and survival of bladder cancer, we targeted the Stat3 signaling pathway in bladder cancer cells using an adenovirus-mediated dominant-negative Stat3 (Y705F and a small molecule compound, STA-21. Both prohibited cell growth and induction of apoptosis in these bladder cancer cell lines but not in normal bladder smooth muscle cell (BdSMC. The survival inhibition might be mediated through apoptotic caspase 3, 8 and 9 pathways. Moreover, down-regulation of anti-apoptotic genes (Bcl-2, Bcl-xL and survivin and a cell cycle regulating gene (cyclin D1 was associated with the cell growth inhibition and apoptosis. Conclusion These results indicated that activation of Stat3 is crucial for bladder cancer cell growth and survival. Therefore, interference of Stat3 signaling pathway emerges as a potential therapeutic approach for bladder cancer.

  11. Cisplatin resistance by induction of aldo-keto reductase family 1 member C2 in human bladder cancer cells

    OpenAIRE

    Shirato, Akitomi; KIKUGAWA, TADAHIKO; Miura, Noriyoshi; Tanji, Nozomu; Takemori, Nobuaki; Higashiyama, Shigeki; Yokoyama, Masayoshi

    2013-01-01

    Cisplatin is currently the most effective anti-tumor agent available against bladder cancer. To clarify the mechanism underlying cisplatin resistance in bladder cancer, the present study examined the role of the aldo-keto reductase family 1 member C2 (AKR1C2) protein on chemoresistance using a human bladder cancer cell line. The function of AKR1C2 in chemoresistance was studied using the human HT1376 bladder cancer cell line and the cisplatin-resistant HT1376-CisR subline. AKR1C2 was expresse...

  12. A study of an effective sunitinib–chemotherapeutic combination regimen for bladder cancer treatment using a mouse model

    Directory of Open Access Journals (Sweden)

    Dah-Shyong Yu

    2014-06-01

    Conclusion: Combination of the tyrosine kinase receptor inhibitor sunitinib with gemcitabine chemotherapy synergistically enhances tumor cytotoxicity and may provide a new treatment modality for advanced bladder cancer.

  13. Quantitative assessment of the relationship between RASSF1A gene promoter methylation and bladder cancer (PRISMA)

    Science.gov (United States)

    Zhan, Leyun; Zhang, Bingyi; Tan, Yaojun; Yang, Chengliang; Huang, Chenhong; Wu, Qiongya; Zhang, Yulin; Chen, Xiaobo; Zhou, Mi; Shu, Aihua

    2017-01-01

    Abstract Background: Methylation of the Ras-association domain family 1 isoform A (RASSF1A) gene promoter region is thought to participate in the initiation and development of many different cancers. However, in bladder cancer the role of RASSF1A methylation was unclear. To evaluate the relationship between RASSF1A methylation and bladder cancer, a quantitative assessment of an independent meta-analysis was performed. In addition, a DNA methylation microarray database from the cancer genome atlas (TCGA) project was used to validate the results of the meta-analysis. Methods: We searched published articles from computerized databases, and DNA methylation data were extracted from TCGA project. All data were analyzed by R software. Results: The results of the meta-analysis indicated that the frequency of RASSF1A gene methylation in bladder cancer patients is significantly higher than in healthy controls. The hazard ratio (HR) was 2.24 (95% CI = [1.45; 3.48], P = 0.0003) for overall survival (OS), and the RASSF1A gene promoter methylation status was strongly associated with the TNM stage and differentiation grade of the tumor. The similar results were also found by the data from TCGA project. Conclusion: There was a significant relationship between the methylation of the RASSF1A gene promoter and bladder cancer. Therefore, RASSF1A gene promoter methylation will be a potential biomarker for the clinical diagnosis of bladder cancer. PMID:28207521

  14. Bladder cancer mortality and private well use in New England: an ecological study

    Science.gov (United States)

    Ayotte, Joseph D; Baris, Dalsu; Cantor, Kenneth P; Colt, Joanne; Robinson, Gilpin R; Lubin, Jay H; Karagas, Margaret; Hoover, Robert N; Fraumeni, Joseph F; Silverman, Debra T

    2006-01-01

    Study objective To investigate the possible relation between bladder cancer mortality among white men and women and private water use in New England, USA, where rates have been persistently raised and use of private water supplies (wells) common. Design Ecological study relating age adjusted cancer mortality rates for white men and women during 1985–1999 and proportion of persons using private water supplies in 1970. After regressing mortality rates on population density, Pearson correlation coefficients were computed between residual rates and the proportion of the population using private water supplies, using the state economic area as the unit of calculation. Calculations were conducted within each of 10 US regions. Setting The 504 state economic areas of the contiguous United States. Participants Mortality analysis of 11 cancer sites, with the focus on bladder cancer. Main results After adjusting for the effect of population density, there was a statistically significant positive correlation between residual bladder cancer mortality rates and private water supply use among both men and women in New England (men, r = 0.42; women, r = 0.48) and New York/New Jersey (men, r = 0.49; women, r = 0.62). Conclusions Use of well water from private sources, or a close correlate, may be an explanatory variable for the excess bladder cancer mortality in New England. Analytical studies are underway to clarify the relation between suspected water contaminants, particularly arsenic, and raised bladder cancer rates in northern New England. PMID:16415269

  15. Pooled analysis and meta-analysis of glutathione S-transferase M1 and bladder cancer: A HuGE review

    DEFF Research Database (Denmark)

    Engel, Lawrence S.; Taioli, Emanuela; Pfeiffer, Ruth;

    2002-01-01

    Smoking is a known risk factor for bladder cancer. The product of the GSTM1 gene, glutathione S-transferase M1 (GSTM1), is involved in the detoxification of polycyclic aromatic hydrocarbons found in tobacco smoke; a homozygous deletion of this gene in approximately 50% of Caucasians and Asians re...

  16. Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Reinert, Thomas; Novoradovsky, A;

    2012-01-01

    Background: Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. Meth...

  17. Distinct pattern of p53 mutations in bladder cancer

    DEFF Research Database (Denmark)

    Spruck, C H; Rideout, W M; Olumi, A F

    1993-01-01

    A distinct mutational spectrum for the p53 tumor suppressor gene in bladder carcinomas was established in patients with known exposures to cigarette smoke. Single-strand conformational polymorphism analysis of exons 5 through 8 of the p53 gene showed inactivating mutations in 16 of 40 (40%) bladder...

  18. Nitrative DNA damage and Oct3/4 expression in urinary bladder cancer with Schistosomahaematobium infection

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Ning [Faculty of Health Science, Suzuka University of Medical Science, Suzuka, Mie (Japan); Thanan, Raynoo [Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie (Japan); Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie (Japan); Kobayashi, Hatasu [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie (Japan); Hammam, Olfat; Wishahi, Mohamed; Leithy, Tarek El [Departments of Pathology and Urology, Theodor Bilharz Research Institute, Giza (Egypt); Hiraku, Yusuke [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie (Japan); Amro, EL-Karef [Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Mie (Japan); Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura (Egypt); Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie (Japan); Ohnishi, Shiho [Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie (Japan); Murata, Mariko [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie (Japan); Kawanishi, Shosuke, E-mail: kawanisi@suzuka-u.ac.jp [Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie (Japan); Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie (Japan)

    2011-10-22

    Highlights: {yields} Oct3/4-positive cells increase in Schistosoma haematobium (SH)-associated bladder cancer. {yields} iNOS-dependent DNA lesion, 8-nitroguanine, was formed in Oct3/4-positive cells. {yields} 8-Nitroguanine formed in stem-like cells plays a role in SH-induced carcinogenesis. {yields} Mutant stem cells may participate in inflammation-related carcinogenesis. -- Abstract: To investigate whether mutant stem cells participate in inflammation-related carcinogenesis, we performed immunohistochemical analysis to examine nitrative and oxidative DNA lesions (8-nitroguanine and 8-oxodG) and a stem cell marker Oct3/4 in bladder tissues obtained from cystitis and bladder cancer patients infected with Schistosomahaematobium (S. haematobium). We also detected the expression of nuclear factor-{kappa}B (NF-{kappa}B) and inducible nitric oxide synthase (iNOS), which lead to 8-nitroguanine formation. The staining intensity of 8-nitroguanine and 8-oxodG was significantly higher in bladder cancer and cystitis tissues than in normal tissues. iNOS expression was colocalized with NF-{kappa}B in 8-nitroguanine-positive tumor cells from bladder cancer patients. Oct3/4 expression was significantly increased in cells from S. haematobium-associated bladder cancer tissues in comparison to normal bladder and cancer tissues without infection. Oct3/4 was also expressed in epithelial cells of cystitis patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in S. haematobium-associated cystitis and cancer tissues. In conclusion, inflammation by S.haematobium infection may increase the number of mutant stem cells, in which iNOS-dependent DNA damage occurs via NF-{kappa}B activation, leading to tumor development.

  19. Asbestos and Cancer Risk

    Science.gov (United States)

    ... Español Category Cancer A-Z What Causes Cancer? Asbestos and Cancer Risk What is asbestos? Asbestos is a group of minerals that occur ... in some countries. How are people exposed to asbestos? People can be exposed to asbestos in different ...

  20. Evaluating Evidence for Association of Human Bladder Cancer with Drinking-Water Chlorination Disinfection By-Products.

    Science.gov (United States)

    Hrudey, Steve E; Backer, Lorraine C; Humpage, Andrew R; Krasner, Stuart W; Michaud, Dominique S; Moore, Lee E; Singer, Philip C; Stanford, Benjamin D

    2015-01-01

    Exposure to chlorination disinfection by-products (CxDBPs) is prevalent in populations using chlorination-based methods to disinfect public water supplies. Multifaceted research has been directed for decades to identify, characterize, and understand the toxicology of these compounds, control and minimize their formation, and conduct epidemiologic studies related to exposure. Urinary bladder cancer has been the health risk most consistently associated with CxDBPs in epidemiologic studies. An international workshop was held to (1) discuss the qualitative strengths and limitations that inform the association between bladder cancer and CxDBPs in the context of possible causation, (2) identify knowledge gaps for this topic in relation to chlorine/chloramine-based disinfection practice(s) in the United States, and (3) assess the evidence for informing risk management. Epidemiological evidence linking exposures to CxDBPs in drinking water to human bladder cancer risk provides insight into causality. However, because of imprecise, inaccurate, or incomplete estimation of CxDBPs levels in epidemiologic studies, translation from hazard identification directly to risk management and regulatory policy for CxDBPs can be challenging. Quantitative risk estimates derived from toxicological risk assessment for CxDBPs currently cannot be reconciled with those from epidemiologic studies, notwithstanding the complexities involved, making regulatory interpretation difficult. Evidence presented here has both strengths and limitations that require additional studies to resolve and improve the understanding of exposure response relationships. Replication of epidemiologic findings in independent populations with further elaboration of exposure assessment is needed to strengthen the knowledge base needed to better inform effective regulatory approaches.

  1. Emerging intravesical therapies for management of nonmuscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Jeffrey J Tomaszewski

    2010-05-01

    Full Text Available Jeffrey J Tomaszewski, Marc C SmaldoneDepartment of Urology, University of Pittsburgh School of Medicine, Pennsylvania, USAAbstract: Transitional cell carcinoma (TCC is the second most common urologic malignancy, and 70% of patients present with superficial or nonmuscle invasive bladder cancer (NMIBC. Intravesical bacillus Calmette-Guerin (BCG is the most effective agent for preventing disease recurrence, and the only therapy able to inhibit disease progression. However, recurrence rates as high as 30% and significant local and systemic toxicity have led to increased interest in alternative intravesical therapies. In patients refractory or intolerant to BCG, BCG-interferon α2b, gemcitabine, and anthracyclines (doxorubicin, epirubicin, valrubicin have demonstrated durable clinical responses. Phase I trials investigating alternative cytotoxic agents, such as apaziquone, taxanes (docetaxel, paclitaxel, and suramin are reporting promising data. Novel immunomodulating agents have demonstrated promise as efficacious alternatives in patients refractory to BCG. Optimization of existing chemotherapeutic regimens using hyperthermia, photodynamic therapy, magnetically-targeted carriers, and liposomes remains an area of active investigation. Despite enthusiasm for new intravesical agents, radical cystectomy remains the treatment of choice for patients with NMIBC who have failed intravesical therapy and selected patients with naïve T1 tumors and aggressive features. This report provides a comprehensive review of contemporary intravesical therapy for NMIBC and refractory NMIBC, with an emphasis on emerging agents and novel treatment modalities.Keywords: transitional cell carcinoma, nonmuscle, invasive, intravesical therapy, BCG

  2. MOLECULAR GENETIC MARKERS AS PREDICTORS OF SUPERFICIAL BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    A. Yu. Babayan

    2009-01-01

    Full Text Available A system of clinical and morphological criteria is currently used to determine the pattern of superficial bladder cancer (SBC. However, this system does not completely reflect the clinical potential of SBC and needs additional markers. The purpose of this study was to search for and evaluate molecular genetic disorders as additional markers of the course of SBC. The diagnostic panel included the deletion of the loci 3р14, 9р21, 9q34, 17р13 (ТР53, mutations of exon 7 of the FGFR3 gene, and hypermethylation of the promoter regions of the RASSF1, RARB, p16, p14, CDH1 genes. The study was made on 108 matched samples (tumor/peripheral blood obtained from patients with SBC. The deletions of the loci 3р14, 9р21 and anomalous methylation of the RARb and p16 genes are markers of the worse course of SBC while FGFR3 gene mutation is a marker of better prognosis. In the context of estimation of the relapsing potential of a primary tumor, the 9p21 locus deletion is a marker associated with recurrence within the first year after malignancy resection. The group of molecular genetic markers determined by the authors for poor prognosis in combination with classical clinical and morphological criteria will specify the pattern of the course of the disease and its prognosis.

  3. Assessment criteria for compensation of occupational bladder cancer.

    Science.gov (United States)

    Schops, Wolfgang; Jungmann, Olaf; Zumbe, Jurgen; Zellner, Michael; Hengstler, Jan G; Golka, Klaus

    2013-01-01

    In Germany, more than 100 bladder tumor cases are annually recognized as occupational disease and compensated, given that medical experts regard exposure to carcinogenic aromatic amines as a likely cause of cancer. The amount of compensation is initially based on the tumor staging and grading at the time of initial diagnosis ("basic MdE") (MdE--reduction of earning capacity) and is adapted after a recurrence-free period of 2 and 5 years, respectively. In the event of treatment or tumor-related secondary conditions, the monthly compensation increases based on the severity of the objectified functional disorder. In the following article, medical experts specializing in this field provide a complete list of all known disorders, including treatment-related loss of a kidney or erectile dysfunction. In addition, the weighting of medical criteria in the assessment and calculation of the compensation is analyzed in greater detail. Since the given criteria are based on comprehensible experiences of urologists with their patients, they also provide medical experts in other countries with valuable points of reference for the calculation of the compensation.

  4. Summary of the 6th Annual Bladder Cancer Think Tank: new directions in urologic research.

    Science.gov (United States)

    Svatek, Robert S; Rosenberg, Jonathan E; Galsky, Matthew D; Lee, Cheryl T; Latini, David M; Bochner, Bernard H; Weizer, Alon Z; Apolo, Andrea B; Sridhar, Srikala S; Kamat, Ashish M; Hansel, Donna; Flaig, Thomas W; Smith, Norm D; Lotan, Yair

    2013-10-01

    The 6th Annual Bladder Cancer Think Tank brought together a multidisciplinary group of clinicians, researchers, and representatives from the National Cancer Institute and Industry in an effort to advance bladder cancer research efforts. This year's meeting comprised panel discussions and research involving 5 separate working groups, including the Survivorship, Clinical Trials, Standardization of Care, Data Mining, and Translational Science working groups. In this manuscript, the accomplishments and objectives of the working groups are summarized. Notable efforts include: (1) the development of a survivorship care plan for early and late-stage bladder cancer; (2) the development of consensus criteria for eligibility and endpoints for bladder cancer clinical trials; (3) an improved understanding of current practice patterns regarding the use of perioperative chemotherapy in an effort to standardize care; (4) creation of a comprehensive handbook to assist researchers with developing bladder cancer databases; and (5) identification of response to therapy of high-grade non muscle invasive disease through a collaborative exchange of expertise and resources.

  5. Metabolism and growth inhibitory activity of cranberry derived flavonoids in bladder cancer cells.

    Science.gov (United States)

    Prasain, Jeevan K; Rajbhandari, Rajani; Keeton, Adam B; Piazza, Gary A; Barnes, Stephen

    2016-09-14

    In the present study, anti-proliferative activities of cranberry derived flavonoids and some of their in vivo metabolites were evaluated using a panel of human bladder tumor cell lines (RT4, SCABER, and SW-780) and non-tumorigenic immortalized human uroepithelial cells (SV-HUC). Among the compounds tested, quercetin 3-O-glucoside, isorhamnetin (3'-O-methylquercetin), myricetin and quercetin showed strong concentration-dependent cell growth inhibitory activities in bladder cancer cells with IC50 values in a range of 8-92 μM. Furthermore, isorhamnetin and myricetin had very low inhibitory activity against SV-HUC even at very high concentrations (>200 μM) compared to bladder cancer cells, indicating that their cytotoxicity is selective for cancer cells. To determine whether the differential cell growth inhibitory effects of isomeric flavonoids quercetin 3-O-glucoside (active) and hyperoside (quercetin 3-O-galactoside) (inactive) are related to their metabolism by the cancer cells, SW-780 cells were incubated with these compounds and their metabolism was examined by LC-MS/MS. Compared to quercetin 3-O-glucoside, hyperoside undergoes relatively less metabolic biotransformation (methylation, glucuronidation and quinone formation). These data suggest that isorhamnetin and quercetin 3-O-glucoside may be the active forms of quercetin in prevention of bladder cancer in vivo and emphasize the importance of metabolism for the prevention of bladder cancer by diets rich in cranberries.

  6. Zinc and copper levels in bladder cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Mao, Song; Huang, Songming

    2013-06-01

    It is well documented that oxidative stress is involved in the pathogenesis of bladder cancer. Zinc (Zn) and copper (Cu) are important components of antioxidants. However, the association between Zn or Cu levels and bladder cancer remains elusive. The present study was designed to investigate the alteration of serum and urinary levels of Zn or Cu in bladder cancer patients compared with controls by performing a systematic review. We searched the PubMed, Embase, and Cochrane databases from January 1990 to March 2013 to identify studies that met our predefined criteria. Six studies were included. Bladder cancer patients demonstrated significantly lower levels of serum Zn (three studies, random effects standard mean deviation (SMD): -1.072, 95 % CI: -1.489 to -0.656, P cancer patients and controls (two studies, random effects SMD: 0.153, 95 % CI: -0.244 to 0.55, P = 0.449). No evidence of publication bias was observed. In conclusion, the disorder of Zn and Cu is closely associated with bladder cancer. Frequent monitoring and early intervention should be recommended.

  7. Radiation treatment planning for bladder cancer: a comparison of cystogram localisation with computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Rothwell, R.I.; Ash, D.V.; Jones, W.G. (Cookridge Hospital, Leeds (UK))

    1983-01-01

    A comparison has been made between the target volumes of radical radiotherapy treatment plans produced with the aid of marker cystograms, and target volumes derived from computed tomography (CT) scans in 60 patients with bladder cancer. This has demonstrated inadequacies of the cystograms due to the inability to delineate extravesical spread of tumour and, as many patients with bladder cancer had a significant residual urine, emptying the bladder by catheterisation may have given a false impression of the shape and size of the target volume. Analysis of the results showed that cystographic localisation resulted in serious underdosage of the tumour in 18% of patients and failure to include all the bladder in 37%. Conventionally produced target volumes showed potentially significant discrepancies in 85% of patients when compared with target volumes delineated by CT.

  8. Novel Gelatin-Adriamycin Sustained Drug Release System for Intravesical Therapy of Bladder Cancer

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To reduce recurrence in the patients with bladder cancer after tumor removal through open surgery or transurethral resection, a form of gelatin-adriamycin sustained drug release system was developed and its release kinetics both in vitro and in vivo, its efficacy in inhibiting BIU-87 bladder tumor cell growth in vitro and its safety in vivo were studied. The results showed that this system controlled adriamycin release over a period of 21 days in vitro and significantly inhibited BIU-87 cell growth. When this system was injected into rabbit bladder, it sustained adriamycin release for 12 days and the released drug could diffuse 1 cm around the injection point. No major complications were observed except minor acute nonspecific cystitis that could be tolerated well by the animals. This study suggests the possibility of applying this system locally in treating bladder cancer.

  9. Effect of oral administration of Shiquandabu pill combined with bladder perfusion chemotherapy on the postoperative recurrence and malignant degree of superficial bladder cancer

    Institute of Scientific and Technical Information of China (English)

    Qiang Zhang; Yi-Shi Xing; Meng-Jia Cui; Zeng-Yue Yang

    2016-01-01

    Objective:To study the effect of oral administration of Shiquandabu pill combined with bladder perfusion chemotherapy on the postoperative recurrence and malignant degree of superficial bladder cancer.Methods:A total of 102 patients with superficial bladder cancer who received transurethral resection of bladder tumor in our hospital between April 2012 and April 2015 were selected and randomly divided into combined group who received postoperative oral administration of Shiquandabu pill combined with bladder perfusion chemotherapy and routine group who received postoperative bladder perfusion chemotherapy, the postoperative tumor recurrence was followed up for 3 years, and the levels of tumor markers in serum as well as the expression levels of stem cell marker molecules and immunoregulation molecules in peripheral blood and recurrent lesions were determined.Results: Postoperative 1-year recurrence rate and postoperative 3-year recurrence rate of combined treatment group were significantly lower than those of routine group, and the mean recurrence time was significantly longer than that of routine group; 1 year after operation, serum VEGF, αFGF,βFGF, MMP2 and MMP9 levels were significantly lower than those of routine group, and ALDH1, Sox2, Nanog, CD47, CD133, B7-H1, PD-1 and PD-L1 mRNA levels in peripheral blood mononuclear cells were significantly lower than those of routine group; after tumor recurrence, ALDH1, Sox2, Nanog, CD47, CD133, B7-H1, PD-1 and PD-L1 mRNA levels in recurrent lesions of combined treatment group were significantly lower than those of routine group.Conclusion:Oral administration of Shiquandabu pill combined with bladder perfusion chemotherapy has better effect on preventing postoperative recurrence of superficial bladder cancer than bladder perfusion chemotherapy alone, and it has regulating effect on tumor load, characteristics of stem cells and immune response after transurethral resection of bladder tumor.

  10. BCG-mediated bladder cancer immunotherapy: identifying determinants of treatment response using a calibrated mathematical model.

    Science.gov (United States)

    Rentsch, Cyrill A; Biot, Claire; Gsponer, Joël R; Bachmann, Alexander; Albert, Matthew L; Breban, Romulus

    2013-01-01

    Intravesical Bacillus Calmette Guérin (BCG) immunotherapy is considered the standard of care for treatment of non-muscle invasive bladder cancer; however the treatment parameters were established empirically. In order to evaluate potential optimization of clinical parameters of BCG induction therapy, we constructed and queried a new mathematical model. Specifically, we assessed the impact of (1) duration between resection and the first instillation; (2) BCG dose; (3) indwelling time; and (4) treatment interval of induction therapy - using cure rate as the primary endpoint. Based on available clinical and in vitro experimental data, we constructed and parameterized a stochastic mathematical model describing the interactions between BCG, the immune system, the bladder mucosa and tumor cells. The primary endpoint of the model was the probability of tumor extinction following BCG induction therapy in patients with high risk for tumor recurrence. We theoretically demonstrate that extending the duration between the resection and the first BCG instillation negatively influences treatment outcome. Simulations of higher BCG doses and longer indwelling times both improved the probability of tumor extinction. A remarkable finding was that an inter-instillation interval two times longer than the seven-day interval used in the current standard of care would substantially improve treatment outcome. We provide insight into relevant clinical questions using a novel mathematical model of BCG immunotherapy. Our model predicts an altered regimen that may decrease side effects of treatment while improving response to therapy.

  11. Intra-fractional bladder motion and margins in adaptive radiotherapy for urinary bladder cancer

    DEFF Research Database (Denmark)

    Grønborg, Caroline; Vestergaard, Anne; Høyer, Morten

    2015-01-01

    BACKGROUND: The bladder is a tumour site well suited for adaptive radiotherapy (ART) due to large inter-fractional changes, but it also displays considerable intra-fractional motion. The aim of this study was to assess target coverage with a clinically applied method for plan selection ART and to...

  12. Small cell cancer of the bladder: The Leon-Berard cancer centre experience

    Directory of Open Access Journals (Sweden)

    Nabil Ismaili

    2008-01-01

    Full Text Available Background: Small cell bladder carcinoma is an uncommon tumor. In this retrospective study we report our experience dealing with this disease at the Leon-Berard Cancer Centre. Materials and Methods: We retrospectively analyzed various characteristics of small cell bladder carcinoma: patient demographics, histological diagnosis, disease stage, treatment effects and outcome, in 14 non-metastatic small cell bladder carcinoma patients treated at our institution between 1995 and 2006. Results: The mean age at diagnosis was 60 years (range, 45-77. All patients were male. Seventy-five per cent were smokers. All had locally advanced disease. Ten patients (71.4% were treated by cystoprostatectomy and bilateral pelvic lymph node resection, one by cystoprostatectomy alone. Two patients received neoadjuvant chemotherapy and four received adjuvant chemotherapy. One patient was treated by radiotherapy with concomitant cisplatin after transurethral resection of bladder tumor (TURBT. One patient refused surgery and was treated by chemotherapy alone. One patient was lost to follow-up after TURBT. After 49-month median follow-up, 12 patients had relapsed. Disease-free survival was 5.7 months. The most frequent sites of relapse were the retroperitoneal lymph node (seven patients and the liver (three patients. Nine patients died of metastasis. Median overall survival was 29.5 months. Survival probability at two years was 58%. Median overall survival was 34 months in the mixed small carcinoma group, as compared with 9.5 months in the pure small cell carcinoma group (P=0.01. Mean overall survival was 27.2 months for all patients and 38.6 months for patients treated with cystectomy and adjuvant chemotherapy. Conclusion: To date, the optimal treatment for locally advanced small cell bladder carcinoma is not clear. Cystectomy with neoadjuvant or adjuvant chemotherapy appears as a viable option.

  13. Sequence variant on 8q24 confers susceptibility to urinary bladder cancer

    Science.gov (United States)

    Kiemeney, Lambertus A.; Thorlacius, Steinunn; Sulem, Patrick; Geller, Frank; Aben, Katja K.H.; Stacey, Simon N.; Gudmundsson, Julius; Jakobsdottir, Margret; Bergthorsson, Jon T.; Sigurdsson, Asgeir; Blondal, Thorarinn; Witjes, J. Alfred; Vermeulen, Sita H.; Hulsbergen-van de Kaa, Christina A.; Swinkels, Dorine W.; Ploeg, Martine; Cornel, Erik B.; Vergunst, Henk; Thorgeirsson, Thorgeir E.; Gudbjartsson, Daniel; Gudjonsson, Sigurjon A.; Thorleifsson, Gudmar; Kristinsson, Kari T.; Mouy, Magali; Snorradottir, Steinunn; Placidi, Donatella; Campagna, Marcello; Arici, Cecilia; Koppova, Kvetoslava; Gurzau, Eugene; Rudnai, Peter; Kellen, Eliane; Polidoro, Silvia; Guarrera, Simonetta; Sacerdote, Carlotta; Sanchez, Manuel; Saez, Berta; Valdivia, Gabriel; Ryk, Charlotta; de Verdier, Petra; Lindblom, Annika; Golka, Klaus; Bishop, D. Timothy; Knowles, Margaret A.; Nikulasson, Sigfus; Petursdottir, Vigdis; Jonsson, Eirikur; Geirsson, Gudmundur; Kristjansson, Baldvin; Mayordomo, Jose I.; Steineck, Gunnar; Porru, Stefano; Buntinx, Frank; Zeegers, Maurice P.; Fletcher, Tony; Kumar, Rajiv; Matullo, Giuseppe; Vineis, Paolo; Kiltie, Anne E.; Gulcher, Jeffrey R.; Thorsteinsdottir, Unnur; Kong, Augustine; Rafnar, Thorunn; Stefansson, Kari

    2015-01-01

    We conducted a genome wide SNP association study on 1,803 Urinary Bladder Cancer (UBC) cases and 34,336 controls from Iceland and the Netherlands and follow up studies in seven additional case control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30kb upstream of the c-Myc gene (allele specific OR=1.22; P=9.34×10−12). Approximately 20% of individuals of European ancestry are homozygous for rs9642880 (T) and their estimated risk of developing UBC is 1.49 times that of non-carriers with population attributable risk (PAR) of 17%. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome wide significance, was captured by rs710521 (A) located near the TP63 gene on chromosome 3q28 (allele specific OR=1.19; P=1. 15× 10−7). PMID:18794855

  14. The route to personalized medicine in bladder cancer: where do we stand?

    Science.gov (United States)

    Massari, Francesco; Ciccarese, Chiara; Santoni, Matteo; Brunelli, Matteo; Conti, Alessandro; Modena, Alessandra; Montironi, Rodolfo; Santini, Daniele; Cheng, Liang; Martignoni, Guido; Cascinu, Stefano; Tortora, Giampaolo

    2015-09-01

    Recent advances in molecular biology and drug design have described novel targets in bladder cancer. EGFR, fibroblast growth factor receptor (FGFR), VEGFR, phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, PD-1, cyclooxygenase 2 (COX-2), Aurora kinase A, and miRNA are just examples of these opening frontiers. In addition, epithelial to mesenchymal transition (EMT) and cancer stem cells (CSCs) are promising candidates for future therapeutic approaches. Novel agents, combination, and sequences are emerging from the 747 clinical studies presently in course in bladder cancer to optimize patient outcomes. This report describes the emerging targets and provides an update on ongoing phase I, II, and III trials and preliminary results on targeted agents, used alone, in sequences, or in combination for patients with bladder cancer.

  15. A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: The future is now.

    Science.gov (United States)

    Bellmunt, Joaquin; Powles, Thomas; Vogelzang, Nicholas J

    2017-03-01

    The treatment of bladder cancer has evolved over time to encompass not only the traditional modalities of chemotherapy and surgery, but has been particularly impacted by the use of immunotherapy. The first immunotherapy was the live, attenuated bacterial Bacillus Calmette-Guérin vaccine, which has been the standard of care non-muscle-invasive bladder cancer since 1990. Modern immunotherapy has focused on inhibitors of checkpoint proteins, which are molecules that impede immune function, thereby allowing tumor cells to grow and proliferate unregulated. Several checkpoint targets (programmed death ligand-1 [PD-L1] programmed cell death protien-1 [PD-1], and cytotoxic T-lymphocyte associated protein 4 [CTLA4]) have received the most attention in the treatment of bladder cancer, and have inhibitor agents either approved or in late-stage development. This review describes the most recent data on agents that inhibit PD-L1, found on the surface of tumor cells, and PD-1 found on activated T and B cells and macrophages. Atezolizumab is the only member of this class currently approved for the treatment of bladder cancer, but nivolumab, pembrolizumab, durvalumab, and avelumab all have positive results for this indication, and approvals are anticipated in the near future. The checkpoint inhibitors offer an effective alternative for patients for whom previously there were few options for durable responses, including those who are ineligible for cisplatin-based regimens or who are at risk of significant toxicity. Research is ongoing to further categorize responses, define ideal patient populations, and investigate combinations of checkpoint inhibitors to address multiple pathways in immune system functioning.

  16. Biopsies of the normal-appearing urothelium in primary bladder cancer

    Directory of Open Access Journals (Sweden)

    Davor Librenjak

    2010-01-01

    Full Text Available Aim: The aim of the study was to determine the incidence of "positive" findings in biopsies of the normal-appearing urothelium near primary cancer and their influence on therapeutic decisions. Materials and Methods: Between January 2001 and October 2008, in 230 patients with primary bladder cancer during initial resection of tumor, we also performed random biopsy of surrounding normal-appearing urothelium. We analyzed retrospectively the number and type of positive biopsy findings and their impact on further treatment. Results: There were 40% of patients (92/230 whose normal-appearing urothelium biopsy revealed pathological findings such as tumor tissue, Tis, and dysplasia. In 24.4% of patients, the stage of the primary tumor was Ta (32/131, in 50% it was T1 stage (30/61, and in 79% T2 stage (30/38. When we assessed the grade of malignancy, we found 18% of biopsies with G1 tumors (16/88, 33% with G2 tumors (19/59, and 69% with G3 tumors (57/83. Tumor tissue that was found in the normal-appearing urothelium in biopsy specimens in 13% of patients was in stage Ta (17/131, in 16% it was T1 stage (10/61, and in 39% of patients, the tumor was in T2 stage (15/38. Pathological findings of random biopsies were crucial in changing therapeutical decisions in 4.6% (9/192 of patients. Conclusion: Biopsy of the normal-appearing urothelial tissue is easy to perform and may help in identifying patients with high risk of disease progression and recurrence. Based on our results and results from the literature we recommend this simple tool as part of the routine management during transurethral resection of primary bladder cancer.

  17. Investigating VMAT planning technique to reduce rectal and bladder dose in prostate cancer treatment plans

    Directory of Open Access Journals (Sweden)

    Suresh B Rana

    2013-01-01

    Full Text Available Background: RapidArc is a volumetric modulated arc therapy (VMAT technique that can deliver conformal dose distribution to the target while minimizing dose to critical structures. The main purpose of this study was to compare dosimetric quality of full double arc (full DA, full single arc (full SA, and partial double arc (partial DA techniques in RapidArc planning of prostate cancer. Materials and Methods: Twelve cases of prostate cancer involving seminal vesicles were selected for this retrospective study. For each case, RapidArc plans were created using full DA (two full arcs, full SA (one full arc, and partial DA (two partial arcs with anterior and posterior avoidance sectors techniques. For planning target volume (PTV, the maximum and mean doses, conformity, and inhomogeneity indices were evaluated. For bladder and rectum, volumes that received 70, 50, 40, and 20 Gy (V 70Gy , V 50Gy , V 40Gy and V 20Gy , respectively, and mean dose were compared. For femoral heads, V 40Gy , V 20Gy , and mean dose were evaluated. Additionally, an integral dose and monitor units (MUs were compared for each treatment plan. Results: In comparison to full DA and full SA techniques, the partial DA technique was better in sparing of rectum and bladder but delivered higher femoral head dose, which was nonetheless within the planning criteria. No clear dosimetric differences were found between full DA and partial DA plans for dose conformity and target homogeneity. The number of MUs and integral dose were largest with the partial DA technique and lowest with the full SA technique. Conclusion: The partial DA technique provides an alternative RapidArc planning approach for low risk prostate cancer.

  18. Acceleration of Apoptosis by Transfection of Bak Gene in Multi-drug Resistant Bladder Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    LIUYing; ZENGFuqing

    2004-01-01

    To study the killing effects of bak gene on multi-drug resistant (MDR) bladder cancer cells and the mechanisms. Methods: Bak gene was transfected into MDR bladder cancer cells by liposome. The expression of bak and Bcl-2 mRNA was detected by in situ hybridization. The expression of bak and Bcl-2 proteins was detected by SABC immunohistochemistry. The growth rate of human bladder cancer cells was studied by constructing the growth curve, cell apoptosis was measured by flow cytometry, and the morphology of cells was observed by fluorescence stain. Results: The expression of bak mRNA was positive in EJ/bak cells (P<0.05). Bak protein expression of EJ/bak cells was positive and Bcl-2 protein expression was decreased (P<0.05). The growth of MDR bladder cancer cells was significantly inhibited after bak gene was transfected (P<0.05). Apoptosis cells were increased significantly. The apoptosis rate was 35%. Apoptotic bodies can be found in these cells by fluorescence stain. Conclusion: Bak gene could inhibit the growth of MDR bladder cancer cells effectively. Inducing cell apoptosis by down-regulating the expression of Bcl-2 gene might be one of its mechanisms.

  19. The softening of human bladder cancer cells happens at an early stage of the malignancy process

    Directory of Open Access Journals (Sweden)

    Jorge R. Ramos

    2014-04-01

    Full Text Available Various studies have demonstrated that alterations in the deformability of cancerous cells are strongly linked to the actin cytoskeleton. By using atomic force microscopy (AFM, it is possible to determine such changes in a quantitative way in order to distinguish cancerous from non-malignant cells. In the work presented here, the elastic properties of human bladder cells were determined by means of AFM. The measurements show that non-malignant bladder HCV29 cells are stiffer (higher Young’s modulus than cancerous cells (HTB-9, HT1376, and T24 cell lines. However, independently of the histological grade of the studied bladder cancer cells, all cancerous cells possess a similar level of the deformability of about a few kilopascals, significantly lower than non-malignant cells. This underlines the diagnostic character of stiffness that can be used as a biomarker of bladder cancer. Similar stiffness levels, observed for cancerous cells, cannot be fully explained by the organization of the actin cytoskeleton since it is different in all malignant cells. Our results underline that it is neither the spatial organization of the actin filaments nor the presence of stress fibers, but the overall density and their 3D-organization in a probing volume play the dominant role in controlling the elastic response of the cancerous cell to an external force.

  20. Polymorphisms in the XRCC1 gene modify survival of bladder cancer patients treated with chemotherapy

    NARCIS (Netherlands)

    Sacerdote, C.; Guarrera, S.; Ricceri, F.; Pardini, B.; Polidoro, S.; Allione, A.; Critelli, R.; Russo, A.; Andrew, A.S.; Ye, Y.; Wu, X.; Kiemeney, L.A.L.M.; Bosio, A.; Casetta, G.; Cucchiarale, G.; Destefanis, P.; Gontero, P.; Rolle, L.; Zitella, A.; Fontana, D.; Vineis, P.; Matullo, G.

    2013-01-01

    Survival of bladder cancer patients depends on several factors including disease stage and grade at diagnosis, age, health status of the patient and the applied treatment. Several studies investigated the role of DNA repair genetic variants in cancer susceptibility, but only few studies investigated

  1. Treatment and outcome in muscle invasive bladder cancer : a population-based survey

    NARCIS (Netherlands)

    Leliveld, Anna M.; Doornweerd, Benjamin H. J.; Bastiaannet, Esther; Schaapveld, Michael; de Jong, Igle J.

    2010-01-01

    OBJECTIVE: To assess treatments and survival of patients with muscle invasive bladder cancer (MIBC) in the Comprehensive Cancer Center Northern Netherlands (CCCN) region. STUDY DESIGN AND SETTING: Retrospective cohort analysis. Data of 548 patients with MIBC diagnosed between 1997 and 2002 were coll

  2. Multifunctional targeting micelle nanocarriers with both imaging and therapeutic potential for bladder cancer

    Directory of Open Access Journals (Sweden)

    Lin TY

    2012-06-01

    Full Text Available Tzu-yin Lin,1 Hongyong Zhang,1 Juntao Luo,2,5 Yuanpei Li,2 Tingjuan Gao,3 Primo N Lara Jr,1,4,6 Ralph de Vere White,4 Kit S Lam,1,2 Chong-Xian Pan,1,3,61Division of Hematology and Oncology, Department of Internal Medicine, 2Department of Biochemistry and Molecular Medicine, 3NSF Center for Biophotonics Science and Technology, School of Medicine, 4Department of Urology, University of California-Davis, Sacramento, CA, 5Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, 6VA Northern California Health Care System, Mather, CA, USABackground: We previously developed a bladder cancer-specific ligand (PLZ4 that can specifically bind to both human and dog bladder cancer cells in vitro and in vivo. We have also developed a micelle nanocarrier drug-delivery system. Here, we assessed whether the targeting micelles decorated with PLZ4 on the surface could specifically target dog bladder cancer cells.Materials and methods: Micelle-building monomers (ie, telodendrimers were synthesized through conjugation of polyethylene glycol with a cholic acid cluster at one end and PLZ4 at the other, which then self-assembled in an aqueous solution to form micelles. Dog bladder cancer cell lines were used for in vitro and in vivo drug delivery studies.Results: Compared to nontargeting micelles, targeting PLZ4 micelles (23.2 ± 8.1 nm in diameter loaded with the imaging agent DiD and the chemotherapeutic drug paclitaxel or daunorubicin were more efficient in targeted drug delivery and more effective in cell killing in vitro. PLZ4 facilitated the uptake of micelles together with the cargo load into the target cells. We also developed an orthotopic invasive dog bladder cancer xenograft model in mice. In vivo studies with this model showed the targeting micelles were more efficient in targeted drug delivery than the free dye (14.3×; P < 0.01 and nontargeting micelles (1.5×; P < 0.05.Conclusion: Targeting micelles decorated with PLZ4 can selectively

  3. Elevated connexin 43 expression in arsenite-and cadmium-transformed human bladder cancer cells, tumor transplants and selected high grade human bladder cancers.

    Science.gov (United States)

    Zhang, Ruowen; Wang, Liping; Garrett, Scott H; Sens, Donald A; Dunlevy, Jane R; Zhou, Xu Dong; Somji, Seema

    2016-10-01

    Connexin 43 has been shown to play a role in cell migration and invasion; however, its role in bladder cancer is not well defined. Previous studies from our laboratory have shown that the environmental pollutants arsenite and cadmium can cause malignant transformation of the immortalized urothelial cell line UROtsa. These transformed cells can form tumors in immune-compromised mice. The goal of the present study was to determine if connexin 43 is expressed in the normal human bladder, the arsenite and cadmiun-transformed UROtsa cells as well as human urothelial cancer. The results obtained showed that connexin 43 is not expressed in the epithelial cells of the human bladder but is expressed in immortalized cultures of human urothelial cells and the expression is variable in the arsenite and cadmium- transformed urothelial cell lines derived from these immortalized cells. Tumor heterotransplants generated from the transformed cells expressed connexin 43 and the expression was localized to areas of squamous differentiation. Immuno-histochemical analysis of human bladder cancers also showed that the expression of connexin 43 was localized to areas of the tumor that showed early features of squamous differentiation. Treatment of UROtsa cells with various concentrations of arsenite or cadmium did not significantly alter the expression level of connexin 43. In conclusion, our results show that the expression of connexin 43 is localized to the areas of the tumor that show squamous differentiation, which may be an indicator of poor prognosis. This suggests that connexin 43 has the potential to be developed as a biomarker for bladder cancer that may have the ability to invade and metastasize.

  4. Specific survivin dual fluorescence resonance energy transfer molecular beacons for detection of human bladder cancer cells

    Institute of Scientific and Technical Information of China (English)

    Zhi-qiang WANG; Jun ZHAO; Jin ZENG; Kai-jie WU; Yu-le CHEN; Xin-ya ng WANG; Luke S CHANG; Da-lin HE

    2011-01-01

    Survivin molecular beacons can be used to detectbladder cancer cells in urine samples non-invasively.The aim of this study is to improve the specificity of detection of bladder cancer cells using survivin dual fluorescence resonance energy transfer molecular beacons (FRET MBs) that have fluorophores forming one donor-acceptor pair.Methods:Survivin-targeting dual fluorescence resonance energy transfer molecular beacons with unique target sequences were designed,which had no overlap with the other genes in the apoptosis inhibitor protein family.Human bladder cancer cell lines 5637,253J and T24,as well as the exfoliated cells in the urine of healthy adults and patients with bladder cancer were examined.Images of cells were taken using a laser scanning confocal fluorescence microscope.For assays using dual FRET MBs,the excitation wavelength was 488 nm,and the emission detection wavelengths were 520+20 nm and 560+20 nm,respectively.Results:The human bladder cancer cell lines and exfoliated cells in the urine of patients with bladder cancer incubated with the survivin dual FRET MBs exhibited strong fluorescence signals.In contrast,no fluorescence was detected in the survivin-negative human dermal fibroblasts-adult (HDF-a) cells or exfoliated cells in the urine of healthy adults incubated with the survivin dual FRET MBs.Conclusion:The results suggest that the survivin dual FRET MBs may be used as a specific and non-invasive method for early detection and follow-up of patients with bladder cancer.

  5. Trends in cancer of the urinary bladder and urinary tract in elderly in Denmark, 2008-2012

    DEFF Research Database (Denmark)

    Jensen, Thor Knak; Jensen, Niels Viggo; Jørgensen, Simon Møller

    2016-01-01

    Background The aim of this study was to examine the trends in incidence, mortality, survival, and prevalence of cancers of the urinary bladder and urinary tract in Denmark from 1980 to 2012 with particular focus on elderly patients over age 70 years. Design Cancer of the urinary bladder and urinary...

  6. Nanoparticulation of BCG-CWS for application to bladder cancer therapy.

    Science.gov (United States)

    Nakamura, Takashi; Fukiage, Masafumi; Higuchi, Megumi; Nakaya, Akihiro; Yano, Ikuya; Miyazaki, Jun; Nishiyama, Hiroyuki; Akaza, Hideyuki; Ito, Toshihiro; Hosokawa, Hiroyuki; Nakayama, Toshinori; Harashima, Hideyoshi

    2014-02-28

    The Mycobacterium bovis Bacille Calmette-Guerin cell wall skeleton (BCG-CWS) could be used to replace live BCG as a bladder cancer drug. However, because BCG-CWS is poorly soluble, has a strong-negative charge, very high molecular weight and heterogeneity in size of tens of μm, it cannot be used in such an application. We report herein on the development of a novel packaging method that permits BCG-CWS to be encapsulated into 166nm-sized lipid particles. The BCG-CWS encapsulated nano particle (CWS-NP) has a high uniformity and can be easily dispersed. Thus, it has the potential for use as a packaging method that would advance the scope of applications of BCG-CWS as a bladder cancer drug. In a functional evaluation, CWS-NP was efficiently taken up by mouse bladder tumor (MBT-2) cells in vitro and inhibited tumor growth in mice bearing MBT-2 tumors. Moreover, intravesically administered CWS-NP showed significant antitumor effects in a rat model with naturally developed bladder cancer. An enhancement in Th1 differentiation by CWS-NP was also confirmed in human T cells. In conclusion, CWS-NP represents a promising delivery system for BCG-CWS for clinical development as a potent bladder cancer drug.

  7. Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer

    KAUST Repository

    Roperch, Jean-Pierre

    2016-09-02

    Background: Non-muscle-invasive bladder cancer (NMIBC) is a high incidence form of bladder cancer (BCa), where genetic and epigenetic alterations occur frequently. We assessed the performance of associating a FGFR3 mutation assay and a DNA methylation analysis to improve bladder cancer detection and to predict disease recurrence of NMIBC patients. Methods: We used allele specific PCR to determine the FGFR3 mutation status for R248C, S249C, G372C, and Y375C. We preselected 18 candidate genes reported in the literature as being hypermethylated in cancer and measured their methylation levels by quantitative multiplex-methylation specific PCR. We selected HS3ST2, SLIT2 and SEPTIN9 as the most discriminative between control and NMIBC patients and we assayed these markers on urine DNA from a diagnostic study consisting of 167 NMIBC and 105 controls and a follow-up study consisting of 158 NMIBC at diagnosis time\\'s and 425 at follow-up time. ROC analysis was performed to evaluate the diagnostic accuracy of each assay alone and in combination. Results: For Diagnosis: Using a logistic regression analysis with a model consisting of the 3 markers\\' methylation values, FGFR3 status, age and known smoker status at the diagnosis time we obtained sensitivity/specificity of 97.6 %/84.8 % and an optimism-corrected AUC of 0.96. With an estimated BCa prevalence of 12.1 % in a hematuria cohort, this corresponds to a negative predictive value (NPV) of 99.6 %. For Follow-up: Using a logistic regression with FGFR3 mutation and the CMI at two time points (beginning of the follow-up and current time point), we got sensitivity/specificity/NPV of 90.3 %/65.1 %/97.0 % and a corrected AUC of 0.84. We also tested a thresholding algorithm with FGFR3 mutation and the two time points as described above, obtaining sensitivity/specificity/NPV values of, respectively, 94.5 %/75.9 %/98.5 % and an AUC of 0.82. Conclusions: We showed that combined analysis of FGFR3 mutation and DNA methylation markers

  8. Biscoumarin derivatives: Synthesis, crystal structure, theoretical studies and induced apoptosis activity on bladder urothelial cancer cell

    Science.gov (United States)

    Xin, Jia-jia; Li, Jing; Zhang, Zi-dan; Hu, Xing-bin; Li, Ming-kai

    2015-03-01

    In this study, five new biscoumarin derivatives (1-5) were synthesized and compound 4 inhibited the proliferation of the bladder urothelial cells (J82 cell line) obviously after 48 h treatment at different concentration (1, 5 and 10 μmol/L), and J82 cells were predominantly induced to apoptotic cell death after compound 4 treatment. Morphologic changes of bladder urothelial cancer cells were also observed under transmission electron microscopy (TEM) after compound 4 treatment. In addition, compound 4 had much less toxicity to human umbilical vein endothelial cells. To explore the possible anti-cancer mechanism of compound 4, two classical intramolecular Osbnd H⋯O hydrogen bonds (HBs) in their structures and the corresponding HB energies were performed with the density functional theory (DFT) [B3LYP/6-31G∗] method. Anti-bladder cancer activity of compound 4 is possible due to the intramolecular weakest HB energies.

  9. THE RECURRENCE AFTER ORGAN-SAVING SURGERY OF PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    T. A. Sveklina

    2014-08-01

    Full Text Available The article represents the study of frequency and nature of the recurrence and survival rate (common, oncology-specific, disease-free after organ-saving surgery of patients with muscle-invasive bladder cancer stages T2b and T3a. Oncology-speсific and disease-free survival rates were much higher if full diagnosis of bladder mucosa, the adjuvant intravesical chemotherapy had been on pre-operative and intra-operative stages than in the absence of these diagnosis and therapy. Recurrentes of bladder cancer which appeared in the absence of diagnosis and combination therapy, statistically reliably occured at another location other than the zone of operation, stage of recurrentes and degree of differentiation of recurrents were less than the original tumor. This information confirms the existence of foci of cancer in situ which have not been identified on the diagnostic stage.

  10. In Vitro and In Vivo Experiments on Electrochemotherapy for Bladder Cancer

    DEFF Research Database (Denmark)

    Vásquez, Juan Luis; Ibsen, Per; Lindberg, Henriette;

    2015-01-01

    PURPOSE: Electrochemotherapy is widely performed to treat solid tumors but experience with bladder cancer is limited. We investigated mitomycin C and cisplatin administered with electrochemotherapy for bladder cancer in vitro and in vivo. MATERIALS AND METHODS: The human bladder cancer cell line SW......780 was used. Cells were treated with electroporation, drug alone or electroporation plus increasing concentrations of drug (mitomycin C 0.001 to 2,000 μM or cisplatin 1.56 to 300 μM). Electrochemotherapy parameters were 8 pulses of 1.2 kV/cm for 99 microseconds at 1 Hz. We investigated survival...... and apoptosis, the latter evaluated by caspase activity. NMRI-Fox1nu nude mice were inoculated subcutaneously and randomized to 1) electrochemotherapy plus NaCl, 2) NaCl alone, 3) electrochemotherapy plus drug or 4) drug alone (mitomycin C 5 mM or cisplatin 250 μM). Tumors were measured 3 times per week...

  11. Evidence-based clinical practice guidelines for bladder cancer (summary - JUA 2009 Edition).

    Science.gov (United States)

    2010-02-01

    In Japan, until now, the treatment of bladder cancer has been based on guidelines from overseas. The problem with this practice is that the options recommended in overseas guidelines are not necessarily suitable for Japanese clinical practice. A relatively large number of clinical trials have been conducted in Japan in the field of bladder cancer, and the Japanese Urological Association (JUA) considered it appropriate to formulate their own guidelines. These Guidelines present an overview of bladder cancer at each clinical stage, followed by clinical questions that address problems frequently faced in everyday clinical practice. In this English translation of a shortened version of the original Guidelines, we have abridged each overview, summarized each clinical question and its answer, and only included the references we considered of particular importance.

  12. Stage-associated overexpression of the ubiquitin-like protein, ISG15, in bladder cancer

    DEFF Research Database (Denmark)

    Andersen, JB; Jensen, Mads Aaboe; Borden, EC;

    2006-01-01

    at different stages of progression. The innate immune response gene, interferon-stimulated gene 15 kDa (ISG15, GIP2), was highly expressed at all stages of bladder cancer as compared to normal urothelium. Western blotting revealed a tumour-associated expression of ISG15 protein. ISG15 exhibited a stage...... expression of ISG15 protein in both cancer cells and stromal immune cells. Interestingly, a significant fraction of ISG15 protein was localised to the nuclei of tumour cells, whereas no nuclear ISG15 staining was observed in ISG15-positive stromal cells. Taken together, our findings identify ISG15 as a novel......Bladder cancer is among the most prevalent malignancies, and is characterised by frequent tumour recurrences and localised inflammation, which may promote tissue invasion and metastasis. Microarray analysis was used to compare gene expression in normal bladder urothelium with that in tumours...

  13. Organ-sparing treatment of advanced bladder cancer. Paclitaxel as a radiosensitizer

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, A.C. [Halle Univ. (Germany). Dept. of Radiation Oncology; Tuebingen Univ. (Germany). Dept. of Radiooncology; Diestelhorst, A.; Kuhnt, T. [Halle Univ. (Germany). Dept. of Radiation Oncology; Kuehn, R. [Martha Maria Hospital Halle (Germany). Dept. of Urology; Fornara, P. [Halle Univ. (Germany). Dept. of Urology; Scholz, H.J. [Asklepios Hospital Weissenfels (Germany). Dept. of Urology; Dunst, J. [Halle Univ. (Germany). Dept. of Radiation Oncology; Luebeck Univ. (Germany). Dept. of Radiation Oncology; Zietman, A.L. [Massachusetts General Hospital, Boston, MA (United States). Dept. of Radiation Oncology

    2007-04-15

    Background and Purpose: Transurethral resection of bladder tumor (TUR-BT) and radiochemotherapy with cisplatin achieve high rates of bladder preservation and survival figures identical to radical cystectomy in muscle-invasive bladder cancers. The authors have investigated the potential use of paclitaxel in a radiochemotherapy protocol for patients with inoperable bladder carcinomas and mainly contraindications to cisplatin. Patients and Methods: Between October 1997 to August 2004, 42 patients (median age 71 years) suffering from muscle-invasive (n = 32) or recurrent (n = 10) bladder cancers were treated with a paclitaxel-containing radiochemotherapy (paclitaxel 25-35 mg/m2 twice weekly) after TUR-BT (R0/1/2/x in n = 18/4/14/3) or cystectomy with residual tumor (n = 3). Five patients received additional cisplatin. Radiation treatment was administered to a total dose of 45-60 Gy. Results: 76.2% completed the planned regimen. Adaptations of treatment were mainly required due to diarrhea. Grade 3/4 toxicities occurred in 15/1 patients. Severe renal toxicities did not occur. 28 patients underwent restaging TUR-BT 6 weeks after radiochemotherapy (complete remission/partial remission/progressive disease: n = 24/3/1). Three patients developed a local recurrence and four distant metastases. Seven patients died from tumor, six of other reasons. Conclusion: Radiochemotherapy with paclitaxel was feasible and this bladder approach needs further investigation to evaluate whether paclitaxel could become a substitute for cisplatin.

  14. Obesity and Cancer Risk

    Science.gov (United States)

    ... GS. Inflammatory mechanisms in obesity. Annual Review of Immunology 2011; 29:415-445. [PubMed Abstract] Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: geographical distribution and risk factors. International Journal ...

  15. A 3-plex methylation assay combined with the FGFR3 mutation assay sensitively detects recurrent bladder cancer in voided urine

    DEFF Research Database (Denmark)

    Kandimalla, Raju; Masius, Roy; Beukers, Willemien;

    2013-01-01

    Purpose: DNA methylation is associated with bladder cancer and these modifications could serve as useful biomarkers. FGFR3 mutations are present in 60% to 70% of non–muscle invasive bladder cancer (NMIBC). Low-grade bladder cancer recurs in more than 50% of patients. The aim of this study......, and nonmalignant urines (n = 130). Results: The 3-plex assay identified recurrent bladder cancer in voided urine with a sensitivity of 74% in the validation set. In combination with the FGFR3 mutation assay, a sensitivity of 79% was reached (specificity of 77%). Sensitivity of FGFR3 and cytology was 52% and 57......%, respectively. Conclusion: The combination of methylation and FGFR3 assays efficiently detects recurrent bladder cancer without the need for stratification of patients regarding methylation/mutation status of the primary tumor. We conclude that the sensitivity of this combination is in the same range...

  16. Transfection of promyelocytic leukemia in retrovirus vector inhibits growth of human bladder cancer cells

    Institute of Scientific and Technical Information of China (English)

    Lei LI; Da-lin HE

    2005-01-01

    Aim: To construct a recombinant retrovirus vector carrying human promyelocytic leukemia (PML) cDNA and identify its expression and biology role in bladder cancer UM-UC-2 cells for future gene therapy. Methods: PML full-length cDNA was inserted into the EcoR I and BamHI site of pLXSN vector containing the long terminal repeat (LTR) promoter. The vector was identified by restriction enzyme digestion and then transfected into PA317 packaging cell line by calcium phosphate coprecipitation. PML cDNA was detected by polymerase chain reaction (PCR) and the protein was identified by laser confocal microscopy and Western blot in bladder cancer cells, respectively. The morphology was observed by inverted phase contrast microscope, and MTT assay determined growth curve of the bladder cancer cells. Results: Restriction enzyme digestion proved that a 2.1kb PML cDNA was inserted into the pLXSN vector. PCR assay demonstrated that 304 bp fragments were found in UM-UC-2/pLPMLSN transfects. Laser confocal microscopy showed speck dots fluorescence in the UM-UC-2/pLPMLSN nucleus.A 90 kD specific brand was found by Western blot. MTT assay demonstrated the UM-UC-2/pLPMLSN bladder cancer growth inhibition. Conclusion: The retrovirus pLPMLSN vector was successfully constructed and could generate high effective expression of human PML in bladder cancer cell UM-UC-2, suggesting that PML recombinant retrovirus have potential utility in the gene therapy for bladder cancer.

  17. The novel bladder preservation therapy BOAI-CDDP-radiation (OMC-regimen): a new treatment option for invasive bladder cancer patients with lymph node metastasis.

    Science.gov (United States)

    Azuma, Haruhito; Inamoto, Teruo; Takahara, Kiyoshi; Nomi, Hayahito; Hirano, Hajime; Ibuki, Naokazu; Uehara, Hiroshi; Komura, Kazumasa; Minami, Koichiro; Uchimoto, Taizo; Saito, Kenkichi; Takai, Tomoaki; Tanda, Naoki; Yamamoto, Kazuhiro; Narumi, Yoshihumi; Kiyama, Satoshi

    2014-06-01

    We have developed a novel bladder preservation therapy for patients with muscle-invasive bladder cancer and lymph node metastasis: balloon-occluded arterial infusion (BOAI) of cisplatin/gemcitabine, with concomitant hemodialysis and irradiation [the so-called 'OMC (Osaka Medical College) regimen']. The OMC regimen delivers an extremely high concentration of anticancer agent to the site of the tumor, as well as the pelvic area, without causing any adverse systemic effects. In this study, we investigated the efficiency of the OMC regimen in 34 patients who underwent BOAI with cisplatin (100, 200 or 300 mg) along with 60 Gy of irradiation; patients who failed to achieve CR underwent secondary BOAI with gemcitabine (1,600 mg). The overall clinical response was 73.5% (CR: 35.3%; PR: 17.6%; SD: 20.6%). The 5-year overall and progression-free survival rates were 54.4% and 52.5%, respectively. For treatment failure, N2 stage was selected as a significant risk factor by simple and multiple logistic regression analyses. Cox proportional hazards analyses showed that N2 stage, T4 stage and the presence of hydronephrosis were significant risk factors for overall survival. Indeed, 55.6% of patients with N1 stage achieved a complete response (CR) (vs. 12.5% for N2 patients, p=0.0151), and 90% (9/10) of the CR patients survived without recurrence with an intact bladder after a mean follow-up of 85 (range 7-193) weeks. The 3-year progrssion-free survival rate with an intact bladder was 65.8% (vs. 37.5% for N2, p=0.034), and the 5-year overall survival rate was 71.8% (vs. 30.6% for N2, p=0.004). No patients suffered severe toxicities of Grade II or more; the oldest patient, aged 85 years, successfully completed this therapy. In conclusion, the OMC regimen can be regarded as a new option for patients with macroscopic lymph node involvement, especially those at stage N1. Therapy will improve the feasibility of radical cure even without the need for cystectomy in patients for whom

  18. A comparison of three different adaptive strategies in image-guided radiotherapy of bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Vestergaard, Anne; Soendergaard, Jimmi; Petersen, Joergen B. (Dept. of Medical Physics, Aarhus Univ. Hospital, Noerrebrogade 44, DK-8000 Aarhus C (Denmark)), E-mail: annveste@rm.dk; Hoeyer, Morten; Muren, Ludvig Paul (Dept. of Oncology, Aarhus Univ. Hospital, Noerrebrogade 44, DK-8000 Aarhus C (Denmark))

    2010-10-15

    The urinary bladder shows considerable individual variation in shape and position during a course of radiotherapy (RT). In this study we have developed and compared three different adaptive RT (ART) strategies for bladder cancer involving daily cone beam CT (CBCT) imaging and plan selection. Material and methods. Ten patients treated for bladder cancer had daily CBCTs acquired that were registered online using bony anatomy registration. Seven patients received intensity modulated RT (IMRT) with a simultaneous integrated boost (SIB) technique to the bladder and pelvic lymph nodes. Three patients received treatment to the bladder only. Retrospectively, we compared three ART strategies that were all based on daily selection of the most suitable plan from a library consisting of three IMRT-plans corresponding to a small, medium and large target volume. ART method A utilised population-based margins while methods B and C used the bladder as seen on CBCT-scans from the first week of treatment; method B without delineation of the bladder on CBCT and method C with delineation of the bladder. Total dose distributions were calculated using the planning CT. For each patient, we calculated ratios of the dose volume histograms (DVHs) for the three ART strategies relative to non-adaptive therapy. Results. The inter-patient variation was large for all three ART strategies. The mean ratios of the volumes receiving 57 Gy or more (corresponding to 95% of prescribed dose) for methods A, B and C were 0.66 (SD: 0.11), 0.67 (SD: 0.13) and 0.67 (SD: 0.16) respectively when compared to the non-adaptive plan. Conclusion. When using any of the ART strategies, it is possible to reduce significantly the volumes receiving high doses compared to the use of a standard non-adaptive plan. The differences in dose volume parameters between the three methods were small compared with the differences from the standard plan.

  19. Inhibiting cell migration and cell invasion by silencing the transcription factor ETS-1 in human bladder cancer.

    Science.gov (United States)

    Liu, Li; Liu, Yuchen; Zhang, Xintao; Chen, Mingwei; Wu, Hanwei; Lin, Muqi; Zhan, Yonghao; Zhuang, Chengle; Lin, Junhao; Li, Jianfa; Xu, Wen; Fu, Xing; Zhang, Qiaoxia; Sun, Xiaojuan; Zhao, Guoping; Huang, Weiren

    2016-05-03

    As one of the members of the ETS gene family, the transcription factor v-ets avian erythroblastosis virus E26 oncogene homolog 1 (ETS-1) plays key role in the regulation of physiological processes in normal cells and tumors. In this study, we aimed to investigate the relationship between the transcription factor ETS-1 and malignant phenotypes of bladder cancer. We demonstrated that ETS-1 was up-regulated in human bladder cancer tissue compared to paired normal bladder tissue. In order to evaluate the functional role of ETS-1 in human bladder cancer, vectors expressing ETS-1 shRNA and ETS-1 protein were constructed in vitro and transfected into the human bladder cancer T24 and 5637 cells. Our results showed that the transcription factor ETS-1 could promote cell migration and cell invasion in human bladder cancer, without affecting cell proliferation and apoptosis. In conclusion, ETS-1 plays oncogenic roles through inducing cell migration and invasion in human bladder cancer, and it can be used as a therapeutic target for treating human bladder cancer.

  20. Sentinel lymph node biopsy in bladder cancer: Systematic review and technology update

    OpenAIRE

    Liss, Michael A.; Noguchi, Jonathan; Lee, Hak J.; Vera, David R.; Kader, A. Karim

    2015-01-01

    A sentinel lymph node (SLN) is the first lymph node to drain a solid tumor and likely the first place metastasis will travel. SLN biopsy has been well established as a staging tool for melanoma and breast cancer to guide lymph node dissection (LND); its utility in bladder cancer is debated. We performed a systematic search of PubMed for both human and animal studies that looked at SLN detection in cases of urothelial carcinoma of the bladder. We identified a total of nine studies that assesse...

  1. The utility of tumour markers in assessing the response to chemotherapy in advanced bladder cancer

    OpenAIRE

    Cook, A M; Huddart, R A; Jay, G; Norman, A.; Dearnaley, D. P.; Horwich, A

    2000-01-01

    In patients with advanced bladder cancer receiving chemotherapy, early assessment of response can avoid unnecessary toxicity. The aim of this study was to assess the role of tumour markers in monitoring response. Serum levels of one or more of markers β human chorionic gonadotrophin (βhCG), carcinoembryomic antigen (CEA), CA125 and CA19.9 were measured in 74 patients with advanced bladder cancer receiving chemotherapy from 1992 to 1997. Forty-three of 74 (58%) of patients had at least one rai...

  2. Understanding your colon cancer risk

    Science.gov (United States)

    Colon cancer - prevention; Colon cancer - screening ... We do not know what causes colon cancer, but we do know some of the things that may increase the risk of getting it, such as: Age. Your risk increases ...

  3. Dietary transfatty acids and cancer risk.

    Science.gov (United States)

    Hu, Jinfu; La Vecchia, Carlo; de Groh, Margaret; Negri, Eva; Morrison, Howard; Mery, Les

    2011-11-01

    This study assesses the association between dietary transfatty acid (TFA) intake and the risk of selected cancers. Mailed questionnaires were completed between 1994 and 1997 in eight Canadian provinces by 1182 incident, histologically confirmed cases of the stomach, 1727 of the colon, 1447 of the rectum, 628 of the pancreas, 3341 of the lung, 2362 of the breast, 442 of the ovary, 1799 of the prostate, 686 of the testis, 1345 of the kidney, 1029 of the bladder, 1009 of the brain, 1666 non-Hodgkin's lymphomas, 1069 leukemias, and 5039 population controls. Information on dietary habits and nutrition intake was obtained using a food frequency questionnaire, which provided data on eating habits 2 years before the study. Odds ratios (OR) and 95% confidenc530e intervals (CI) were derived by unconditional logistic regression to adjust for total energy intake and other potential confounding factors. Dietary TFA were positively associated with the risk of cancers of the colon (OR: 1.38 for the highest vs. the lowest quartile), breast in premenopause (OR: 1.60), and prostate (OR: 1.42). There were a borderline association for pancreas cancer (OR: 1.38; P=0.06). No significant association was observed for cancers of the stomach, rectum, lung, ovary, testis, kidney, bladder, brain, non-Hodgkin's lymphomas, and leukemia, although the ORs for the highest quartile were above unity for all neoplasms considered, except testis. Our findings add evidence that high TFA is associated with an increased risk of various cancers. Thus, a diet low in transfat may play a role in the prevention of several cancers.

  4. Proteomic analysis of urinary biomarker candidates for nonmuscle invasive bladder cancer.

    Science.gov (United States)

    Lindén, Mårten; Lind, Sara Bergström; Mayrhofer, Corina; Segersten, Ulrika; Wester, Kenneth; Lyutvinskiy, Yaroslav; Zubarev, Roman; Malmström, Per-Uno; Pettersson, Ulf

    2012-01-01

    Nonmuscle invasive tumors of the bladder often recur and thereby bladder cancer patients need regular re-examinations which are invasive, unpleasant, and expensive. A noninvasive and less expensive method, e.g. a urine dipstick test, for monitoring recurrence would thus be advantageous. In this study, the complementary techniques mass spectrometry (MS) and Western blotting (WB)/dot blot (DB) were used to screen the urine samples from bladder cancer patients. High resolving MS was used to analyze and quantify the urinary proteome and 29 proteins had a significantly higher abundance (pblot for four selected proteins; fibrinogen β chain precursor, apolipoprotein E, α-1-antitrypsin, and leucine-rich α-2-glycoprotein 1. Dot blot analysis of an independent urine sample set pointed out fibrinogen β chain and α-1-antitrypsin as most interesting biomarkers having sensitivity and specificity values in the range of 66-85%. Exploring the Human Protein Atlas (HPA) also revealed that bladder cancer tumors are the likely source of these proteins. They have the potential of being useful in diagnosis, monitoring of recurrence and thus may improve the treatment of bladder tumors, especially nonmuscle invasive tumors.

  5. A RETROSPECTIVE STUDY OF THE EFFICACY OF CHEMOIRRADIATION IN LOCALLY ADVANCED URINARY BLADDER CANCER

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    Nehru

    2015-04-01

    Full Text Available BACKGROUND : Radical cystectomy with pelvic lymph node dissection is the standard method used to treat patients with locally advanced carcinoma of urinary bladder. Furthermore, a significant proportion of patients are deemed unsuitable for surgery due to inoperability, advanced age, and/or comorbid conditions. B ecause of disappointing results with radical cystectomy in terms of survival, as well as the morbidity and decreased quality of life associated with the surgery, bladder - conserving therapies like trimodality (TURBT, concurrent chemoradiation therapy have been gained popularity as the survival rates are nearly equal with radical cystectomy along with functioning bladder. AIM OF STUDY : To study retrospectively the effectiveness of chemoradition therapy in bladder preservation approach in the management of p atients with locally advanced ( I nvasive bladder cancer in medically unfit and unwilling patients for radical cystectomy and those who cannot tolerate combination chemotherapy drugs. METHOD S AND MATERIAL : The data was collected from the patient’s records between 2004 - 2010 who were treated in our Regional cancer hospital. All were biopsy/CT scan proven muscle invasive urinary bladder tumors with T2 – 3, N0, M0 lesions. Post TURBT status. Medi cally unfit and Unwillingness for surgery and underwent concurrent Radiotherapy with weekly cisplatin therapy. And men and / women with age between 45 - 70 years were included in the study. RESULTS : Out of 28 patients 4 (14.29% patients who had good TURP procedure showed complete response , 20(71.43% patients had partial response and 4(14.29% patients showed stable disease. 71.43% patient showed symptomatic response to treatment . CONCLUSION : Being a single agent chemotherapy with radiation and it is feasible without major toxicity and offers a potentially usefulness in locoregional control and symptomatic relief in unfavorable population with invasive bladder cancer. Moreover it

  6. Bladder cancer: utility of MRI in detection of occult muscle-invasive disease

    Energy Technology Data Exchange (ETDEWEB)

    Rosenkrantz, Andrew B. [Dept. of Radiology, NYU Langone Medical Center, New York (United States)], E-mail: Andrew.rosenkrantz@nyumc.org; Mussi, Thais C. [Dept. of Radiology, NYU Langone Medical Center, New York (United States); Hospital Israelita Albert Einstein, Sao Paulo (Brazil); Melamed, Jonathan [Dept. of Pathology, NYU Langone Medical Center, New York (United States); Taneja, Samir S.; Huang, William C. [Dept. of Urology, Div. of Urologic Oncology, NYU Langone Medical Center, New York (United States)

    2012-07-15

    Background. The presence of muscularis propria invasion by bladder cancer is a key factor in prognosis and treatment decisions, although may be missed by biopsy due to sampling error. MRI has shown potential for detection of muscle invasion but has not specifically been evaluated for this purpose in the setting of bladder cancer patients without evidence of muscle invasion on initial biopsy. Purpose. To evaluate the role of MRI in detection of muscularis propria invasion by bladder cancer following a pathologic diagnosis of non-invasive tumor. Material and Methods. This retrospective study included 23 patients who underwent pelvic MRI following a pathologic diagnosis of bladder cancer without muscularis propria invasion and in whom additional histologic evaluation was performed following MRI. Two radiologists in consensus reviewed T2-weighted images to identify those cases suspicious for muscle invasion on MRI. The radiologists identified whether cases suspicious for invasion demonstrated disruption of the T2-hypointense muscularis layer of the bladder wall, peri-vesical fat stranding, and peri-vesical soft tissue nodularity. Findings were compared with pathologic results obtained after MRI. Results. Suspicion was raised for muscle invasion in eight of 23 cases, four of which exhibited invasion on follow-up pathology. No case without suspicion on MRI exhibited invasion on follow-up pathology. Therefore, sensitivity and specificity were 100% and 79%, respectively. Among individual findings, muscularis disruption on T2WI exhibited sensitivity of 100% and specificity of 79%, peri-vesical fat stranding exhibited sensitivity and specificity of 50% and 84%, and peri-vesical soft tissue nodularity exhibited sensitivity and specificity of 25% and 100%. Conclusion. MRI demonstrated high sensitivity for detection of muscle invasion in cases of bladder cancer without invasion on initial histologic assessment. Muscularis disruption on T2WI appeared to exhibit a better

  7. Combined systemic therapy and radiotherapy for bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Roedel, C.; Weiss, C. [Dept. of Radiotherapy and Oncology, Univ. of Frankfurt (Germany); Sauer, R. [Dept. of Radiotherapy, Univ. of Erlangen (Germany)

    2007-12-15

    The standard of care for transitional-cell carcinoma of the bladder with invasion to the muscularis propria is radical cystectomy. Sophisticated techniques for urinary diversion have been developed to improve patients' quality of life. Even the construction of a neobladder with continent urinary diversion, however, cannot substitute for the patient's original bladder. Attempts to obtain organ preservation are only justified when they have a high likelihood of achieving local cure with no compromise in survival rates. Adequate local control cannot be achieved with transurethral resection of the bladder tumor (TURBT), chemotherapy, or radiotherapy, when used alone. Several groups have reported the value of combining all three modalities, with salvage cystectomy being reserved for patients with incomplete response or local relapse. (orig.)

  8. Malakoplakia mimics urinary bladder cancer: A case report

    Directory of Open Access Journals (Sweden)

    Ristić-Petrović Ana

    2013-01-01

    Full Text Available Introduction. Malakoplakia is an unusual and very rare chronic inflammatory disease. In bladder especially it can mimic malignancy and lead to serious misdiagnosis. Case report. We presented a case of a middle-aged woman with persistent macrohematuria and cystoscopically polypoid bladder mass that resembled a neoplastic process. The final diagnosis was based on cystoscopic biopsy and microscopic findings of acidophilic, foamy histiocytes with the presence of Michaelis-Gutmann inclusions which are characteristic for diagnosis of malakoplakia. Immunohistochemistry confirmed diagnosis by demonstrating CD68-positive macrophages. Conclusion. Urinary bladder malakoplakia should be considered in patients with persistent urinary tract infections and tumor mass at cystoscopy. Early identification with prompt antibiotic treatment can be helpful in avoiding unnecessary surgical interventions and in preventing development of possible complications. [Projekat Ministarstva nauke Republike Srbije, br. 175092

  9. Levels of certain tumor markers as differential factors between bilharzial and non-biharzial bladder cancer among Egyptian patients

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    Mohamed Azza M

    2011-04-01

    Full Text Available Abstract Background/Objective Bladder cancer is the commonest type of malignant tumors as a result of schistosomaisis which is a major healthy problem in many subtropical developing countries. The aim of this study is to comparatively elucidate the underlying biochemical tumor markers in schistosomal bladder cancer versus non-schistosomal bladder cancer when compared to normal healthy ones. Methods This work was performed on tissue specimens from total 25 patients and serum samples from total 30 patients versus ten healthy individuals served as control. The investigated parameters in serum are: xanthine oxidase (XO, fructosamine, lactate dehydrogense (LDH, aspartate aminotransferase (AST, alanine aminotransferase (ALT, total proteins, essential and non- essential amino acids profile, hydroxyproline, total immunoglobulin E (IgE and tumor necrosis factor alpha (TNF-α. In addition, the current investigation also extended to study some markers in tumor bladder tissues including, pyruvate kinase enzyme (PK, lactate dehydrogenase (LDH, aspartate aminotransferase (AST and alanine aminotransferase (ALT. Results Results showed that biharzial bladder cancer patients recored more significant elevation in serum XO, fructosamine, LDH, AST, ALT, hydroxyproline, IgE and TNF-α than in bladder cancer patients when compared to control ones. While, in tissues there were significant increase in PK, LDH, AST & ALT activities of schistosomal bladder cancer than in bladder cancer as compared to control healthy patients. Conclusions It could be concluded that, bilharzial and non-bilharzial bladder cancer showed distinct biochemical profile of tumor development and progression which can be taken into consideration in diagnosis of bladder cancer.

  10. Clinical impact of bladder biopsies with TUR-BT according to cytology results in patients with bladder cancer: a case control study

    Directory of Open Access Journals (Sweden)

    Matsumoto Kazuhiro

    2010-06-01

    Full Text Available Abstract Background There seems to be no consensus concerning taking bladder biopsies during transurethral resection of bladder tumor (TUR-BT. We investigate the clinical significance of bladder biopsy with TUR-BT and the relationship between urinary cytology and the biopsy results. Methods We reviewed a total of 424 patients with non-muscle invasive bladder cancer treated with TUR-BT between 1998 and 2005. Of the total, 293 patients also underwent a bladder biopsy. Biopsies from suspicious-appearing urothelium (N = 59 and those from normal-appearing urothelium (N = 234 were evaluated separately. Results Bladder cancer was observed in 23 cases (39.0% who underwent a biopsy of suspicious-appearing urothelium. Among these 23 cases, 9 cases with visible tumor resection had carcinoma in situ (CIS only in the biopsies from suspicious-appearing urothelium. Urinary cytology was negative in 3 of the 9 cases. Bladder cancer was observed in 26 cases (11.1% who underwent a biopsy of normal-appearing urothelium. Of them, 5 cases with visible tumors had CIS only in the multiple biopsies from normal-appearing urothelium. Urinary cytology was positive in all of the 5 cases. No upstaging or upgrading cases were found in these patients by the addition of these two types of biopsy. Furthermore, therapy was not altered in these patients. With or without bladder biopsy was not a significant factor for tumor recurrence in either the univariate or multivariate analysis. Conclusions Based on the results, it is concluded the multiple biopsies from normal-appearing urothelium are not necessary in patients with negative cytology results because of the low detection rate and lack of influence on therapeutic decisions. Meanwhile, biopsy of suspicious-appearing urothelium is needed in patients with negative cytology results in order to detect CIS due to staging properties. This result supports a recent EAU guideline.

  11. ATM participates in the regulation of viability and cell cycle via ellipticine in bladder cancer

    Science.gov (United States)

    Tao, Shuixiang; Meng, Shuai; Zheng, Xiangyi; Xie, Liping

    2017-01-01

    Ellipticine, an alkaloid isolated from Apocyanaceae plants, has been demonstrated to exhibit antitumor activity in several cancers. However, the effect and the mechanisms underlying its action have not been investigated in human bladder cancer cells. The aim of the present study was to investigate the effect and mechanism of ellipticine on the behavior of T-24 bladder cancer cells. T-24 cells were treated with varying concentrations and durations of ellipticine. Cell viability was evaluated by Cell Counting Kit-8 assay. Cell motility was analyzed by Transwell migration assay. Flow cytometry, reverse transcription-quantitative polymerase chain reaction and western blot analyses were performed to detect the cell cycle and signaling pathways involved. The results demonstrated that ellipticine suppressed proliferation and inhibited the migration ability of T-24 bladder cancer cells in a dose- and time-dependent manner, and resulted in G2/M cell cycle arrest. The mechanism of this action was demonstrated to be due to ellipticine-triggered activation of the ATM serine/threonine kinase pathway. These data therefore suggest that ellipticine may be effective towards treating human bladder cancer. PMID:28138703

  12. Selection of microsatellite markers for bladder cancer diagnosis without the need for corresponding blood.

    Directory of Open Access Journals (Sweden)

    Angela A G van Tilborg

    Full Text Available Microsatellite markers are used for loss-of-heterozygosity, allelic imbalance and clonality analyses in cancers. Usually, tumor DNA is compared to corresponding normal DNA. However, normal DNA is not always available and can display aberrant allele ratios due to copy number variations in the genome. Moreover, stutter peaks may complicate the analysis. To use microsatellite markers for diagnosis of recurrent bladder cancer, we aimed to select markers without stutter peaks and a constant ratio between alleles, thereby avoiding the need for a control DNA sample. We investigated 49 microsatellite markers with tri- and tetranucleotide repeats in regions commonly lost in bladder cancer. Based on analysis of 50 blood DNAs the 12 best performing markers were selected with few stutter peaks and a constant ratio between peaks heights. Per marker upper and lower cut off values for allele ratios were determined. LOH of the markers was observed in 59/104 tumor DNAs. We then determined the sensitivity of the marker panel for detection of recurrent bladder cancer by assaying 102 urine samples of these patients. Sensitivity was 63% when patients were stratified for LOH in their primary tumors. We demonstrate that up-front selection of microsatellite markers obliterates the need for a corresponding blood sample. For diagnosis of bladder cancer recurrences in urine this significantly reduces costs. Moreover, this approach facilitates retrospective analysis of archival tumor samples for allelic imbalance.

  13. Prima-1 induces apoptosis in bladder cancer cell lines by activating p53

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    Camila B. Piantino

    2013-01-01

    Full Text Available OBJECTIVES: Bladder cancer represents 3% of all carcinomas in the Brazilian population and ranks second in incidence among urological tumors, after prostate cancer. The loss of p53 function is the main genetic alteration related to the development of high-grade muscle-invasive disease. Prima-1 is a small molecule that restores tumor suppressor function to mutant p53 and induces cancer cell death in various cancer types. Our aim was to investigate the ability of Prima-1 to induce apoptosis after DNA damage in bladder cancer cell lines. METHOD: The therapeutic effect of Prima-1 was studied in two bladder cancer cell lines: T24, which is characterized by a p53 mutation, and RT4, which is the wild-type for the p53 gene. Morphological features of apoptosis induced by p53, including mitochondrial membrane potential changes and the expression of thirteen genes involved in apoptosis, were assessed by microscopic observation and quantitative real-time PCR (qRT-PCR. RESULTS: Prima-1 was able to reactivate p53 function in the T24 (p53 mt bladder cancer cell line and promote apoptosis via the induction of Bax and Puma expression, activation of the caspase cascade and disruption of the mitochondrial membrane in a BAK-independent manner. CONCLUSION: Prima-1 is able to restore the transcriptional activity of p53. Experimental studies in vivo may be conducted to test this molecule as a new therapeutic agent for urothelial carcinomas of the bladder, which characteristically harbor p53 mutations.

  14. Alternative splicing in colon, bladder, and prostate cancer identified by exon-array analysis

    DEFF Research Database (Denmark)

    Thorsen, Kasper; Sørensen, Karina D.; Brems-Eskildsen, Anne Sofie;

    2008-01-01

    Alternative splicing enhances proteome diversity and modulates cancer-associated proteins. To identify tissue- and tumor-specific alternative splicing, we used the GeneChip Human Exon 1.0 ST Array to measure whole-genome exon expression in 102 normal and cancer tissue samples of different stages......, and 18 candidate tumor-specific splicing alterations in colon, bladder, and prostate, respectively, were selected for RT-PCR validation on an independent set of 81 normal and tumor tissue samples. In total, seven genes with tumor-specific splice variants were identified (ACTN1, CALD1, COL6A3, LRRFIP2...... from colon, urinary bladder, and prostate. We identified 2069 candidate alternative splicing events between normal tissue samples from colon, bladder, and prostate and selected 15 splicing events for RT-PCR validation, 10 of which were successfully validated by RT-PCR and sequencing. Furthermore 23, 19...

  15. The Use of Regenerative Medicine in the Management of Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Matthew E. Hyndman

    2012-01-01

    Full Text Available Muscle invasive and recurrent nonmuscle invasive bladder cancers have been traditionally treated with a radical cystectomy and urinary diversion. The urinary diversion is generally accomplished through the creation of an incontinent ileal conduit, continent catheterizable reservoir, or orthotopic neobladder utilizing small or large intestine. While radical extirpation of the bladder is often successful from an oncological perspective, there is a significant morbidity associated with enteric interposition within the genitourinary tract. Therefore, there is a great opportunity to decrease the morbidity of the surgical management of bladder cancer through utilization of novel technologies for creating a urinary diversion without the use of intestine. Clinical trials using neourinary conduits (NUC seeded with autologous smooth muscle cells are currently in progress and may represent a significant surgical advance, potentially eliminating the complications associated with the use of gastrointestinal segments in the urinary reconstruction, simplifying the surgical procedure, and greatly facilitating recovery from cystectomy.

  16. A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

    Science.gov (United States)

    Kiemeney, Lambertus A; Sulem, Patrick; Besenbacher, Soren; Vermeulen, Sita H; Sigurdsson, Asgeir; Thorleifsson, Gudmar; Gudbjartsson, Daniel F; Stacey, Simon N; Gudmundsson, Julius; Zanon, Carlo; Kostic, Jelena; Masson, Gisli; Bjarnason, Hjordis; Palsson, Stefan T; Skarphedinsson, Oskar B; Gudjonsson, Sigurjon A; Witjes, J Alfred; Grotenhuis, Anne J; Verhaegh, Gerald W; Bishop, D Timothy; Sak, Sei Chung; Choudhury, Ananya; Elliott, Faye; Barrett, Jennifer H; Hurst, Carolyn D; de Verdier, Petra J; Ryk, Charlotta; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Vineis, Paolo; Polidoro, Silvia; Guarrera, Simonetta; Sacerdote, Carlotta; Campagna, Marcello; Placidi, Donatella; Arici, Cecilia; Zeegers, Maurice P; Kellen, Eliane; Gutierrez, Berta Saez; Sanz-Velez, José I; Sanchez-Zalabardo, Manuel; Valdivia, Gabriel; Garcia-Prats, Maria D; Hengstler, Jan G; Blaszkewicz, Meinolf; Dietrich, Holger; Ophoff, Roel A; van den Berg, Leonard H; Alexiusdottir, Kristin; Kristjansson, Kristleifur; Geirsson, Gudmundur; Nikulasson, Sigfus; Petursdottir, Vigdis; Kong, Augustine; Thorgeirsson, Thorgeir; Mungan, N Aydin; Lindblom, Annika; van Es, Michael A; Porru, Stefano; Buntinx, Frank; Golka, Klaus; Mayordomo, José I; Kumar, Rajiv; Matullo, Giuseppe; Steineck, Gunnar; Kiltie, Anne E; Aben, Katja K H; Jonsson, Eirikur; Thorsteinsdottir, Unnur; Knowles, Margaret A; Rafnar, Thorunn; Stefansson, Kari

    2010-01-01

    Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 × 10−12). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC. PMID:20348956

  17. Inter-application displacement of brachytherapy dose received by the bladder and rectum of the patients with inoperable cervical cancer

    Science.gov (United States)

    Marosevic, Goran; Ljuca, Dzenita; Osmic, Hasan; Fazlic, Semir; Arsovski, Oliver; Mileusnic, Dusan

    2014-01-01

    Background The aim of the study was to examine on the CT basis the inter-application displacement of the positions D0.1cc, D1cc and D2cc of the brachytherapy dose applied to the bladder and rectum of the patients with inoperable cervical cancer. Patients and methods This prospective study included 30 patients with cervical cancer who were treated by concomitant chemo-radiotherapy. HDR intracavitary brachytherapy was made by the applicators type Fletcher tandem and ovoids. For each brachytherapy application the position D0.1cc was determined of the bladder and rectum that receive a brachytherapty dose. Then, based on the X, Y, and Z axis displacement, inter-application mean X, Y, and Z axis displacements were calculated as well as their displacement vectors (R). It has been analyzed whether there is statistically significant difference in inter-application displacement of the position of the brachytherapy dose D0.1cc, D1cc and D2cc of the bladder and rectum. The ANOVA test and post-hoc analysis by Tukey method were used for testing statistical importance of differences among the groups analyzed. The difference among the groups analyzed was considered significant if p < 0.05. Results There are significant inter-application displacements of the position of the brachytherapy dose D0,1cc, D1cc and D2cc of the bladder and rectum. Conclusions When we calculate the cumulative brachytherapy dose by summing up D0,1cc, D1cc and D2cc of the organs at risk for all the applications, we must bear in mind their inter-application displacement, and the fact that it is less likely that the worst scenario would indeed happen. PMID:24991211

  18. Tissue polypeptide antigen in the follow-up of patients with urinary bladder cancer compared with conventional urine cytology.

    Science.gov (United States)

    Bantis, Athanasios; Zissimopoulos, Athanasios; Sountoulides, Petros; Giannakopoulos, Stilianos; Kalaitzis, Christos; Athanassiadou, Paulina; Agelonidou, Eleni; Touloupidis, Stavros

    2010-01-01

    The incidence of bladder cancer has demonstrated a rapid increase during the last decades. The aim of this study is to determine the clinical value of serum tissue polypeptide antigen (TPA) as a tumour marker for urinary bladder cancer in comparison with conventional urine cytology. Urine and blood samples were obtained from a total of 108 patients (group A) with a known history of bladder cancer, who presented for their routine 3 month follow-up. These 108 patients included 45 patients with high grade and 63 patients with low grade bladder cancer, and 30 patients with lower urinary tract symptoms (LUTS) and no history of bladder cancer (group B). Urine and blood samples from fifty healthy adults (group C) were also tested; this group served as the control group for estimating the normal range of serum TPA values. In all group A patients cystoscopy and/or bladder biopsies were performed. All blood and urine samples were tested for TPA and conventional urine cytology respectively. Results showed that the upper normal range for TPA was 1.0 ng/mL(0.9 ± 0.04) in the control group. For the subgroups of patients with high and low grade bladder cancer elevated serum TPA levels were found in 52% and 40% of the patients respectively. The overall serum TPA sensitivity and specificity were 50% and 85% respectively for patients with known bladder cancer (group A). We found the sensitivity of cytology for high grade bladder (GIII) carcinomas to be 72%; however when urine cytology was combined with serum TPA the overall sensitivity reached 80%. We conclude that serum TPA combined with urine cytology may be used as a prognostic marker for bladder cancer.

  19. Risk of second primary cancer following prostate cancer radiotherapy: DVH analysis using the competitive risk model

    Science.gov (United States)

    Takam, R.; Bezak, E.; Yeoh, E. E.

    2009-02-01

    This study aimed to estimate the risk of developing second primary cancer (SPC) corresponding to various radiation treatment techniques for prostate cancer. Estimation of SPC was done by analysing differential dose-volume histograms (DDVH) of normal tissues such as rectum, bladder and urethra with the competitive risk model. Differential DVHs were obtained from treatment planning systems for external beam radiotherapy (EBRT), low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy techniques. The average risk of developing SPC was no greater than 0.6% for all treatment techniques but was lower with either LDR or HDR brachytherapy alone compared with any EBRT technique. For LDR and HDR brachytherapy alone, the risk of SPC for the rectum was 2.0 × 10-4% and 8.3 × 10-5% respectively compared with 0.2% for EBRT using five-field 3D-CRT to a total dose of 74 Gy. Overall, the risk of developing SPC for urethra following all radiation treatment techniques was very low compared with the rectum and bladder. Treatment plans which deliver equivalent doses of around 3-5 Gy to normal tissues were associated with higher risks of development of SPC.

  20. Risk of second primary cancer following prostate cancer radiotherapy: DVH analysis using the competitive risk model

    Energy Technology Data Exchange (ETDEWEB)

    Takam, R; Bezak, E [School of Chemistry and Physics, University of Adelaide, Adelaide (Australia); Yeoh, E E [School of Medicine, University of Adelaide, Adelaide (Australia)], E-mail: Rungdham.Takam@health.sa.gov.au

    2009-02-07

    This study aimed to estimate the risk of developing second primary cancer (SPC) corresponding to various radiation treatment techniques for prostate cancer. Estimation of SPC was done by analysing differential dose-volume histograms (DDVH) of normal tissues such as rectum, bladder and urethra with the competitive risk model. Differential DVHs were obtained from treatment planning systems