Current trends in the management of bladder cancer.

PubMed

Patel, Amit R; Campbell, Steven C

2009-01-01

This article provides a review of bladder cancer etiology, diagnosis, and management for WOC nurses. Bladder cancer incidence continues to rise yearly in the United States, and patients with bladder cancer comprise some of the most challenging cases in urologic oncology. Nurses are involved with all aspects of the processes of care for the patient with bladder cancer, from initial diagnosis and treatment to postsurgical care and follow-up. For nonmuscle invasive bladder cancer, treatment includes transurethral resection followed by intravesical chemotherapy or immunotherapy to prevent recurrence or progression. Radical cystectomy along with chemotherapy protocols provides a survival advantage for muscle invasive bladder cancer, although the timing of chemotherapy remains controversial. Numerous factors are considered when determining the type of urinary diversion used at the time of radical cystectomy, but patient, family, surgeon, and nursing input are essential for preserving an optimal health-related quality of life and reducing morbidity. Patients with metastatic bladder cancer are generally treated with a cisplatin-based chemotherapy but continue to have a poor prognosis. Newer therapies involving novel molecular-targeted agents provide hope for the future for patients with metastatic disease.

Fluorescent imaging of high-grade bladder cancer using a specific antagonist for chemokine receptor CXCR4.

PubMed

Nishizawa, Koji; Nishiyama, Hiroyuki; Oishi, Shinya; Tanahara, Noriko; Kotani, Hirokazu; Mikami, Yoshiki; Toda, Yoshinobu; Evans, Barry J; Peiper, Stephen C; Saito, Ryoichi; Watanabe, Jun; Fujii, Nobutaka; Ogawa, Osamu

2010-09-01

We previously reported that the expression of CXC chemokine receptor-4 (CXCR4) was upregulated in invasive bladder cancers and that the small peptide T140 was a highly sensitive antagonist for CXCR4. In this study, we identified that CXCR4 expression was induced in high-grade superficial bladder tumors, including carcinoma in situ and invasive bladder tumors. To visualize the bladder cancer cells using urinary sediments from the patients and chemically induced mouse bladder cancer model, a novel fluorescent CXCR4 antagonist TY14003 was developed, that is a T140 derivative. TY14003 could label bladder cancer cell lines expressing CXCR4, whereas negative-control fluorescent peptides did not label them. When labeling urinary sediments from patients with invasive bladder cancer, positive-stained cells were identified in all patients with bladder cancer and positive urine cytology but not in controls. Although white blood cells in urine were also labeled with TY14003, they could be easily discriminated from urothelial cells by their shape and size. Finally, intravesical instillation of TY14003 into mouse bladder, using N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder cancer model, demonstrated that fluorescent signals were detected in the focal areas of bladder of all mice examined at 12 weeks of BBN drinking by confocal microscopy and fluorescent endoscopy. On the contrary, all the normal bladders were found to be negative for TY14003 staining. In conclusion, these results indicate that TY14003 is a promising diagnostic tool to visualize small or flat high-grade superficial bladder cancer.

Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM.

PubMed

Bryan, R T; Regan, H L; Pirrie, S J; Devall, A J; Cheng, K K; Zeegers, M P; James, N D; Knowles, M A; Ward, D G

2015-03-17

Better biomarkers must be found to develop clinically useful urine tests for bladder cancer. Proteomics can be used to identify the proteins released by cancer cell lines and generate candidate markers for developing such tests. We used shotgun proteomics to identify proteins released into culture media by eight bladder cancer cell lines. These data were compared with protein expression data from the Human Protein Atlas. Epidermal growth factor receptor (EGFR) was identified as a candidate biomarker and measured by ELISA in urine from 60 noncancer control subjects and from 436 patients with bladder cancer and long-term clinical follow-up. Bladder cancer cell lines shed soluble EGFR ectodomain. Soluble EGFR is also detectable in urine and is highly elevated in some patients with high-grade bladder cancer. Urinary EGFR is an independent indicator of poor bladder cancer-specific survival with a hazard ratio of 2.89 (95% CI 1.81-4.62, P<0.001). In multivariable models including both urinary EGFR and EpCAM, both biomarkers are predictive of bladder cancer-specific survival and have prognostic value over and above that provided by standard clinical observations. Measuring urinary EGFR and EpCAM may represent a simple and useful approach for fast-tracking the investigation and treatment of patients with the most aggressive bladder cancers.

Fruit and vegetable intake and the risk of recurrence in patients with non-muscle invasive bladder cancer: a prospective cohort study.

PubMed

Jochems, Sylvia H J; van Osch, Frits H M; Reulen, Raoul C; van Hensbergen, Mitch; Nekeman, Duncan; Pirrie, Sarah; Wesselius, Anke; van Schooten, Frederik-Jan; James, Nicholas D; Wallace, D Michael A; Bryan, Richard T; Cheng, K K; Zeegers, Maurice P

2018-06-01

There is some evidence that greater consumption of fruit and vegetables decreases the risk of bladder cancer. The role of fruit and vegetables in bladder cancer recurrence is still unknown. The role of total fruit and vegetable intake in relation to the risk of developing bladder cancer recurrence in a prospective cohort study. 728 patients with non-muscle invasive bladder cancer (NMIBC), who completed self-administrated questionnaires on fruit and vegetable intake at time of diagnosis (over the year before diagnosis) and 1 year after diagnosis, were included. Hazard ratios and 95% confidence intervals were calculated by multivariable Cox regression for developing recurrent bladder cancer in relation to fruit and vegetable intake. During 2,051 person-years of follow-up [mean (SD) follow-up 3.7 (1.5) years], 241 (33.1%) of the included 728 NMIBC patients developed a recurrence of bladder cancer. The sum of total fruit and vegetables before diagnosis was not related to a first bladder cancer recurrence (HR 1.07; 95% CI 0.78-1.47, p = 0.66). No association was found between greater consumption of fruit and vegetables over the year before diagnosis and the risk of developing multiple recurrences of bladder cancer (HR 1.02; 95% CI 0.90-1.15, p = 0.78). Among the remaining 389 NMIBC patients who reported on fruit and vegetable intake 1 year after diagnosis, no association was found between greater consumption of fruit and vegetables and a first recurrence of bladder cancer (HR 0.65; 95% CI 0.42-1.01, p = 0.06) nor with multiple recurrences of bladder cancer (HR 1.00, 95% CI 0.85-1.18, p = 1.00). Similar results were obtained when investigating the association between total intakes of fruit and vegetables separately and bladder cancer recurrence. Results from this study did not indicate a protective role for total fruit and vegetables in the development of a recurrence of NMIBC.

Expression analysis and clinical significance of CXCL16/CXCR6 in patients with bladder cancer.

PubMed

Lee, Jun Taik; Lee, Sang Don; Lee, Jeong Zoo; Chung, Moon Kee; Ha, Hong Koo

2013-01-01

The interactions between chemokines and their receptors are closely involved in the progression and metastasis of cancer. We hypothesized that the CXCL16-CXCR6 ligand-receptor system plays an important role in bladder cancer progression. To evaluate this hypothesis, the expression levels of CXCL16 and CXCR6 were evaluated in 160 patients, including 155 patients with bladder cancer and 5 patients with benign bladder disease. The tissues were analyzed by immunohistochemical (IHC) staining and real-time reverse-transcription polymerase chain reaction. We compared the expression of CXCL16/CXCR6 in bladder cancer and benign bladder disease. The expression of CXCR6 was increased in patients with bladder cancer compared with benign bladder disease in RT-PCR. The mRNA expression levels of CXCL16 and CXCR6 were 1.75×10(-2) and 1.99×10(-2) in benign bladder tissue and 1.39×10(-2) and 2.32×10(-2) in bladder cancer tissue, respectively. In IHC staining, the expression of CXCL16/CXCR6 in bladder cancer tissues was higher compared with benign bladder tissues. On multivariate analysis, the IHC staining of CXCL16 was correlated with the 2004 WHO grade and lymphovascular invasion (P=0.021 and P=0.011, respectively). CXCR6 was correlated with the 1973 WHO grade (P=0.001), 2004 WHO grade (P<0.001), pathological T stage (P=0.002) and perineural invasion (P=0.031). However, Cox regression analysis revealed that the expression of CXCL16 and CXCR6 was not correlated with cancer recurrence and cancer-specific survival (P=0.142 and P=0.324, respectively). The expression of CXCL16/CXCR6 was higher in bladder cancer compared to benign disease and correlated with aggressive cancer behavior. Based on our results, the CXCL16/CXCR6 axis appears to be important in the progression of bladder cancer. Thus, CXCL16 and CXCR6 serve as potential therapeutic targets.

Occupational risks for bladder cancer among men in Sweden.

PubMed

Malker, H S; McLaughlin, J K; Silverman, D T; Ericsson, J L; Stone, B J; Weiner, J A; Malker, B K; Blot, W J

1987-12-15

With the use of the Swedish Cancer-Environment Registry, census data on employment in 1960 were linked with registry data on bladder cancer during 1961-79. This hypothesis-generating study revealed for the first time associations between bladder cancer and employment in pulp and fiberboard manufacturing, in rope and twine making, and work as a dental technician. Statistically significant increases in risk were also found for several occupations previously associated with bladder cancer, including barbers and beauticians, artistic painters, toolmakers and machinists, and physicians, and employment in butcher shops, industrial chemical making, apparel manufacturing, and plumbing. Etiologic inferences cannot be made from this investigation, but the findings from this large national resource provide further clues to the occupational determinants of bladder cancer.

Bladder cancer, a review of the environmental risk factors.

PubMed

Letašiová, Silvia; Medve'ová, Alžbeta; Šovčíková, Andrea; Dušinská, Mária; Volkovová, Katarína; Mosoiu, Claudia; Bartonová, Alena

2012-06-28

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. 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. 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. Smoking, in particular from cigarettes, exposure to arsenic in drinking water, and occupational exposure to aromatic amines and 4,4'-methylenebis(2-chloroaniline) are well known risk factors for various diseases including bladder cancer. Although the number of chemicals related to occupational exposure is still growing, it is worth noting that it may take several years or decades between exposure and the subsequent cancer.

Bladder cancer: overview and disease management. Part 1: non-muscle-invasive bladder cancer.

PubMed

Anderson, Beverley

2018-05-10

Part 1 of this two-part article provides an overview of bladder cancer and discusses its management. Since publication of a previous article entitled 'Understanding the role of smoking in the aetiology of bladder cancer' ( Anderson, 2009 ), the author has received many requests for an update. This article provides an overview of bladder cancer and its current management practices, underlining the continued role of smoking as the predominant risk factor in the disease's development. The management of bladder cancer is governed by specific guidelines. Management of non-muscle-invasive cancers, including surgical intervention with transurethral resection, and intravesical therapy using chemotherapy and immunotherapy agents, is discussed. Cystectomy (removal of the bladder), is sometimes necessary. Treatments are effective in reducing tumour recurrence, but the effects of the risks and side-effects on the individual's quality of life can be significant. The prevalence of bladder cancer, and the nature of its management make this cancer one of the most expensive for the NHS to treat. The effectiveness of health promotional strategies in increasing peoples' awareness of their risk of developing the disease, and in enabling them to change long-term health behaviours is discussed. The role of the multidisciplinary team is explored, along with that of the uro-oncology cancer nurse specialist. Part 2 will consider the management of muscle-invasive and metastatic bladder cancer.

Benign Prostatic Hyperplasia and the Risk of Prostate Cancer and Bladder Cancer

PubMed Central

Dai, Xiaoyu; Fang, Xiangming; Ma, Ying; Xianyu, Jianbo

2016-01-01

Abstract Benign prostatic hyperplasia (BPH) has been suggested to be a risk factor for certain urologic cancers, but the current evidence is inconsistent. The aim of this study was to investigate the association between BPH and urologic cancers. MEDLINE, EMBASE, Cochrane Library, and Web of Science were searched for potential eligible studies. We included case-control studies or cohort studies, which evaluated the association between BPH and urologic cancers (including prostate cancer, bladder cancer, kidney cancer, testicular cancer, or penile cancer). Overall effect estimates were calculated using the DerSimonian–Laird method for a random-effects model. Summary effect-size was calculated as risk ratio (RR), together with the 95% confidence interval (CI). This systematic review included 16 case-control studies and 10 cohort studies evaluating the association of BPH and prostate or bladder cancer; we did not identify any study about other urologic cancers. Meta-analyses demonstrated that BPH was associated with an increased incidence of prostate cancer (case-control study: RR = 3.93, 95% CI = 2.18–7.08; cohort-study: RR = 1.41, 95% CI = 1.00–1.99) and bladder cancer (case-control study: RR = 2.50, 95% CI = 1.63–3.84; cohort-study: RR = 1.58, 95% CI = 1.28–1.95). Subgroup analysis by ethnicity suggested that the association between BPH and prostate cancer was much stronger in Asians (RR = 6.09, 95% CI = 2.96–12.54) than in Caucasians (RR = 1.54, 95% CI = 1.19–2.01). Egger's tests indicated low risk of publication bias (prostate cancer: P = 0.11; bladder cancer: P = 0.95). BPH is associated with an increased risk of prostate cancer and bladder cancer. The risk of prostate cancer is particularly high in Asian BPH patients. Given the limitations of included studies, additional prospective studies with strict design are needed to confirm our findings. PMID:27149447

Drugs Approved for Bladder Cancer

Cancer.gov

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.

Chronic Infections of the Urinary Tract and Bladder Cancer Risk: a Systematic Review.

PubMed

Anderson-Otunu, Oghenetejiri; Akhtar, Saeed

2016-01-01

Literature on the relationship between recurrent urinary tract infections and urinary bladder carcinoma risk has been inconsistent. Therefore, we carried out this systematic review of observational studies to ascertain if there is any association between chronic urinary tract infection and urinary bladder carcinoma. A total of 10 databases were searched using Boolean: CINAHL, PUBMED, Google Scholar, Medline, Science Direct, SCIRUS, Cochrane, UK PubMed central, NHS evidence and WHO-website. The search yielded an initial hit of 3,518 articles and after screening and critical appraisal, seven studies were included for this review. Four articles reported an association between chronic urinary tract infections and bladder cancer while three concluded a weak or no association at least in one gender. Main findings in this review were that most of the studies reported an association between chronic urinary tract infections and bladder cancer risk. However, inferences about the causal association between chronic urinary tract infections and bladder cancer risk should be drawn cautiously considering the methodological limitations of case-control studies included in this review. Therefore, more empirical evidence is needed to determine the causal nature of relationships between chronic urinary tract infections and bladder cancer risk.

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

PubMed

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.

Prompt diagnosis key in bladder cancer.

PubMed

DeSouza, Karen; Chowdhury, Simon; Hughes, Simon

2014-01-01

Bladder cancer is the most frequently diagnosed cancer involving the urinary tract and is the seventh most common cancer in the UK. Delayed diagnosis is associated with high-grade muscle invasive disease which has the potential to progress rapidly, metastasise and is often fatal. Urothelial cancer (transitional cell carcinoma) is the predominant histological subtype in Europe, where it accounts for 90% of all bladder cancers. Haematuria, which is typically intermittent, frank, painless and at times present throughout micturition, is the classical and most common presentation of bladder cancer. However, irritative symptoms such as dysuria, urgency, urge incontinence and frequency as well as obstructive symptoms can also be experienced. Fatigue; weight loss; anorexia; renal failure; respiratory symptoms and a suprapubic palpable mass are usually signs of advanced or metastatic malignancy. Cigarette smokers have up to four times the risk of bladder cancer compared with non-smokers. Other risk factors include: exposure to aniline dyes; use of cyclophosphamide; history of pelvic radiation; exposure to chemical carcinogens associated with certain industries; spinal cord injuries requiring long-term indwelling catheters; type 2 diabetes treated with pioglitazone and condylomata acuminata. Frank haematuria has a high diagnostic yield for malignancies involving the urinary tract and initial routine tests should be directed towards identifying a variety of potential non-malignant causes. A thorough physical examination should be undertaken to identify evidence of bleeding diathesis and metastatic malignancy. Suggested laboratory investigations include FBC, coagulation, creatinine and PSA. The diagnosis of bladder cancer is based on urine cytology, cystoscopy and pathological assessment of the bladder biopsy.

Increased expression of GGN promotes tumorigenesis in bladder cancer and is correlated with poor prognosis.

PubMed

Wang, Wentao; Li, Changfu; Chen, Yongsheng; Teng, Lichen; Cao, Yan; Xu, Yongpeng; Pan, Hongxin; An, Ruihua

2018-04-30

Bladder cancer has shown great challenge for people's life. Traditional therapeutics against bladder cancer including surgery could not bring much benefit for patients, particularly for the late stage patients. So it is necessary to keep in mind why and how bladder cancer cells survive in our body. In this study, we explored the function and the molecular mechanism of GGN gene in bladder cancer. GGN was shown to be expressed at a high level in bladder cancer tissues compared to the control and was associated with the unsatisfactory survival rate of patients. GGN was also expressed abundantly in bladder cancer cell lines such as T24, 5637 and BIU87. Then GGN was knocked down in 5637 cells and T24 cells at both RNA and protein level. In accordance, aberrant growth and proliferation were demonstrated in bladder cancer cells. The ability of migration and invasion of bladder cancer cells was also inhibited. The in vivo data further proved that the xenograft tumor growth was dramatically suppressed by GGN knockdown. Then we demonstrated that the level of IκB, bax and truncated caspase3 was upregulated after GGN was knocked down in 5637 cells. In contrast, expression level of NFκB, IKK, c-Myc, cyclin D1 and Bcl-2 was reduced. Further, the phosphorylation level of IκB was also downregulated. These data suggest that NFκB/caspase3-mediated apoptosis signaling was regulated by GGN. Conclusively, GGN played a tumor-promoting role in bladder cancer through regulation of NFκB/caspase3-mediated apoptosis signaling. This study provides a new clue for the treatment of patients with bladder cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

mTORC2 activation is regulated by the urokinase receptor (uPAR) in bladder cancer.

PubMed

Hau, Andrew M; Leivo, Mariah Z; Gilder, Andrew S; Hu, Jing-Jing; Gonias, Steven L; Hansel, Donna E

2017-01-01

Mammalian target of rapamycin complex 2 (mTORC2) has been identified as a major regulator of bladder cancer cell migration and invasion. Upstream pathways that mediate mTORC2 activation remain poorly defined. Urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored membrane protein and known activator of cell-signaling. We identified increased uPAR expression in 94% of invasive human bladder cancers and in 54-71% of non-invasive bladder cancers, depending on grade. Normal urothelium was uPAR-immunonegative. Analysis of publicly available datasets identified uPAR gene amplification or mRNA upregulation in a subset of bladder cancer patients with reduced overall survival. Using biochemical approaches, we showed that uPAR activates mTORC2 in bladder cancer cells. Highly invasive bladder cancer cell lines, including T24, J82 and UM-UC-3 cells, showed increased uPAR mRNA expression and protein levels compared with the less aggressive cell lines, UROtsa and RT4. uPAR gene-silencing significantly reduced phosphorylation of Serine-473 in Akt, an mTORC2 target. uPAR gene-silencing also reduced bladder cancer cell migration and Matrigel invasion. S473 phosphorylation was observed by immunohistochemistry in human bladder cancers only when the tumors expressed high levels of uPAR. S473 phosphorylation was not controlled by uPAR in bladder cancer cell lines that are PTEN-negative; however, this result probably did not reflect altered mTORC2 regulation. Instead, PTEN deficiency de-repressed alternative kinases that phosphorylate S473. Our results suggest that uPAR and mTORC2 are components of a single cell-signaling pathway. Targeting uPAR or mTORC2 may be beneficial in patients with bladder cancer. Copyright © 2016. Published by Elsevier Inc.

Bladder cancer incidence among workers exposed to o-toluidine, aniline and nitrobenzene at a rubber chemical manufacturing plant

PubMed Central

Carreón, Tania; Hein, Misty J; Hanley, Kevin W; Viet, Susan M; Ruder, Avima M

2015-01-01

Background An earlier investigation found increased bladder cancer incidence among workers at a rubber chemical manufacturing plant that used o-toluidine, aniline and nitrobenzene. The cohort was expanded to include additional workers (n=1875) and updated through 2007 to assess bladder cancer with improved exposure characterisation. Methods Work histories were updated and exposure categories and ranks were developed for o-toluidine, aniline and nitrobenzene combined. Incident cancers were identified by linkage to six state cancer registries. Residency in time-dependent cancer registry catchment areas was determined. SIR and standardised rate ratios for bladder cancer were calculated by exposure category and cumulative rank quartiles for different lag periods. Cox regression was used to model bladder cancer incidence with estimated cumulative rank, adjusting for confounders. Indirect methods were used to control for smoking. Results Excess bladder cancer was observed compared to the New York State population (SIR=2.87, 95% CI 2.02 to 3.96), with higher elevations among workers definitely exposed (moderate/high) (SIR=3.90, 95% CI 2.57 to 5.68), and in the highest cumulative rank quartile (SIR=6.13, 95% CI 2.80 to 11.6, 10-year lag). Bladder cancer rates increased significantly with estimated cumulative rank (10-year lag). Smoking only accounted for an estimated 8% elevation in bladder cancer incidence. Conclusions Bladder cancer incidence remains elevated in this cohort and significantly associated with estimated cumulative exposure. Results are consistent with earlier findings in this and other cohorts. Despite other concurrent chemical exposures, we consider o-toluidine most likely responsible for the bladder cancer incidence elevation and recommend a re-examination of occupational exposure limits. PMID:24368697

Expression analysis and clinical significance of CXCL16/CXCR6 in patients with bladder cancer

PubMed Central

LEE, JUN TAIK; LEE, SANG DON; LEE, JEONG ZOO; CHUNG, MOON KEE; HA, HONG KOO

2013-01-01

The interactions between chemokines and their receptors are closely involved in the progression and metastasis of cancer. We hypothesized that the CXCL16-CXCR6 ligand-receptor system plays an important role in bladder cancer progression. To evaluate this hypothesis, the expression levels of CXCL16 and CXCR6 were evaluated in 160 patients, including 155 patients with bladder cancer and 5 patients with benign bladder disease. The tissues were analyzed by immunohistochemical (IHC) staining and real-time reverse-transcription polymerase chain reaction. We compared the expression of CXCL16/CXCR6 in bladder cancer and benign bladder disease. The expression of CXCR6 was increased in patients with bladder cancer compared with benign bladder disease in RT-PCR. The mRNA expression levels of CXCL16 and CXCR6 were 1.75×10−2 and 1.99×10−2 in benign bladder tissue and 1.39×10−2 and 2.32×10−2 in bladder cancer tissue, respectively. In IHC staining, the expression of CXCL16/CXCR6 in bladder cancer tissues was higher compared with benign bladder tissues. On multivariate analysis, the IHC staining of CXCL16 was correlated with the 2004 WHO grade and lymphovascular invasion (P=0.021 and P=0.011, respectively). CXCR6 was correlated with the 1973 WHO grade (P=0.001), 2004 WHO grade (P<0.001), pathological T stage (P=0.002) and perineural invasion (P=0.031). However, Cox regression analysis revealed that the expression of CXCL16 and CXCR6 was not correlated with cancer recurrence and cancer-specific survival (P=0.142 and P=0.324, respectively). The expression of CXCL16/CXCR6 was higher in bladder cancer compared to benign disease and correlated with aggressive cancer behavior. Based on our results, the CXCL16/CXCR6 axis appears to be important in the progression of bladder cancer. Thus, CXCL16 and CXCR6 serve as potential therapeutic targets. PMID:23255926

A place for precision medicine in bladder cancer: targeting the FGFRs.

PubMed

di Martino, Erica; Tomlinson, Darren C; Williams, Sarah V; Knowles, Margaret A

2016-10-01

Bladder tumors show diverse molecular features and clinical outcome. Muscle-invasive bladder cancer has poor prognosis and novel approaches to systemic therapy are urgently required. Non-muscle-invasive bladder cancer has good prognosis, but high recurrence rate and the requirement for life-long disease monitoring places a major burden on patients and healthcare providers. Studies of tumor tissues from both disease groups have identified frequent alterations of FGFRs, including mutations of FGFR3 and dysregulated expression of FGFR1 and FGFR3 that suggest that these may be valid therapeutic targets. We summarize current understanding of the molecular alterations affecting these receptors in bladder tumors, preclinical studies validating them as therapeutic targets, available FGFR-targeted agents and results from early clinical trials in bladder cancer patients.

A place for precision medicine in bladder cancer: targeting the FGFRs

PubMed Central

di Martino, Erica; Tomlinson, Darren C; Williams, Sarah V; Knowles, Margaret A

2016-01-01

Bladder tumors show diverse molecular features and clinical outcome. Muscle-invasive bladder cancer has poor prognosis and novel approaches to systemic therapy are urgently required. Non-muscle-invasive bladder cancer has good prognosis, but high recurrence rate and the requirement for life-long disease monitoring places a major burden on patients and healthcare providers. Studies of tumor tissues from both disease groups have identified frequent alterations of FGFRs, including mutations of FGFR3 and dysregulated expression of FGFR1 and FGFR3 that suggest that these may be valid therapeutic targets. We summarize current understanding of the molecular alterations affecting these receptors in bladder tumors, preclinical studies validating them as therapeutic targets, available FGFR-targeted agents and results from early clinical trials in bladder cancer patients. PMID:27381494

Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer.

PubMed

Kauffman, Eric C; Robinson, Brian D; Downes, Martin J; Powell, Leagh G; Lee, Ming Ming; Scherr, Douglas S; Gudas, Lorraine J; Mongan, Nigel P

2011-12-01

Bladder cancer is approximately three times more common in men as compared to women. We and others have previously investigated the contribution of androgens and the androgen receptor (AR) to bladder cancer. JMJD2A and LSD1 are recently discovered AR coregulator proteins that mediate AR-dependent transcription via recently described histone lysine-demethylation (KDM) mechanisms. We used immunohistochemistry to examine JMJD2A, LSD1, and AR expression in 72 radical cystectomy specimens, resulting in evaluation of 129 tissue samples (59 urothelial carcinoma, 70 benign). We tested levels of these proteins for statistical association with clinicopathologic variables and patient survival. Expression of these markers was also assessed in human bladder cancer cell lines. The effects of pharmacological inhibition of LSD1 on the proliferation of these bladder cancer cells was determined. JMJD2A and AR levels were significantly lower in malignant versus benign urothelium, while increased LSD1 levels were observed in malignant urothelium relative to benign. A significant reduction in all three proteins occurred with cancer stage progression, including muscle invasion (JMJD2A/LSD1/AR), extravesical extension (JMJD2A/LSD1), and lymph node metastasis (JMJD2A/AR). Lower JMJD2A intensity correlated with additional poor prognostic features, including lymphovascular invasion, concomitant carcinoma in situ and tobacco usage, and predicted significantly worse overall survival. Pharmacological inhibition of LSD1 suppressed bladder cancer cell proliferation and androgen-induced transcription. Our results support a novel role for the AR-KDM complex in bladder cancer initiation and progression, identify JMJD2A as a promising prognostic biomarker, and demonstrate targeting of the KDM activity as an effective potential approach for bladder cancer growth inhibition. Copyright © 2011 Wiley Periodicals, Inc.

Evaluation of associations between lifetime exposure to drinking water disinfection by-products and bladder cancer in dogs.

PubMed

Backer, Lorraine C; Coss, Angela M; Wolkin, Amy F; Flanders, W Dana; Reif, John S

2008-06-01

To assess the risk of bladder cancer in dogs from exposure to drinking water disinfection by-products and determine whether dogs could serve as sentinels for human bladder cancer associated with such exposures. Case-control study. 100 dogs with cancer of the urinary bladder and 100 control dogs. Case and control dogs were frequency-matched by age (within 2 years) and sex. Owners of dogs enrolled provided verbal informed consent and were interviewed by telephone. The telephone questionnaire included a complete residence history for each dog. Each dog's total exposure history to trihalomethanes was reconstructed from its residence history and corresponding drinking water utility company data. No association was detected between increasing years of exposure to chlorinated drinking water and risk of bladder cancer. Dogs with bladder cancer were exposed to higher total trihalomethanes concentrations than control dogs; however, the difference was not significant. Although humans and their dogs live in the same household, the activity patterns of dogs may lead to lower exposures to household tap water. Thus, although exposure to disinfection by-products in tap water may be a risk factor for human bladder cancer, this may not be true for canine bladder cancer at the concentrations at which dogs are exposed.

Bladder Diseases

MedlinePlus

... 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

Bladder cancer, a review of the environmental risk factors

PubMed Central

2012-01-01

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) are well known risk factors for various diseases including bladder cancer. Although the number of chemicals related to occupational exposure is still growing, it is worth noting that it may take several years or decades between exposure and the subsequent cancer. PMID:22759493

Mitomycin C Intravesical Chemotherapy in Conjunction With Synergo® Radiofrequency-Induced Hyperthermia for Treatment of Carcinoma in Situ Non-Muscle Invasive Bladder Cancer Patients Unresponsive to Bacillus Calmette-Guérin, With or Without Papillary Tumors.

ClinicalTrials.gov

2018-03-20

Bladder Cancer; Bladder Neoplasm; Bladder Tumors; Cancer of Bladder; Cancer of the Bladder; Malignant Tumor of Urinary Bladder; Neoplasms, Bladder; Urinary Bladder Cancer; Carcinoma in Situ of Bladder; Papillary Carcinoma of Bladder (Diagnosis); BCG-Unresponsive Bladder Cancer

Bladder Cancer Mortality in the United States: A Geographic and Temporal Analysis of Socioeconomic and Environmental Factors.

PubMed

Smith, Norm D; Prasad, Sandip M; Patel, Amit R; Weiner, Adam B; Pariser, Joseph J; Razmaria, Aria; Maene, Chieko; Schuble, Todd; Pierce, Brandon; Steinberg, Gary D

2016-02-01

We assessed the association of temporal, socioeconomic and environmental factors with bladder cancer mortality in the United States. Our hypothesis was that bladder cancer mortality is associated with distinct environmental and socioeconomic factors with effects varying by region, race and gender. NCI (National Cancer Institute) age adjusted, county level bladder cancer mortality data from 1950 to 2007 were analyzed to identify clusters of increased bladder cancer death using the Getis-Ord Gi* statistic. Socioeconomic, clinical and environmental data were assessed using geographically weighted spatial regression analysis adjusting for spatial autocorrelation. County level socioeconomic, clinical and environmental data were obtained from national databases, including the United States Census, CDC (Centers for Disease Control and Prevention), NCHS (National Center for Health Statistics) and County Health Rankings. Bladder cancer mortality hot spots and risk factors for bladder cancer death differed significantly by gender, race and geographic region. From 1996 to 2007 smoking, unemployment, physically unhealthy days, air pollution ozone days, percent of houses with well water, employment in the mining industry and urban residences were associated with increased rates of bladder cancer mortality (p <0.05). Model fit was significantly improved in hot spots compared to all American counties (R(2) = 0.20 vs 0.05). Environmental and socioeconomic factors affect bladder cancer mortality and effects appear to vary by gender and race. Additionally there were temporal trends of bladder cancer hot spots which, when persistent, should be the focus of individual level studies of occupational and environmental factors. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Application of Multi-SNP Approaches Bayesian LASSO and AUC-RF to Detect Main Effects of Inflammatory-Gene Variants Associated with Bladder Cancer Risk

PubMed Central

Calle, M. Luz; Rothman, Nathaniel; Urrea, Víctor; Kogevinas, Manolis; Petrus, Sandra; Chanock, Stephen J.; Tardón, Adonina; García-Closas, Montserrat; González-Neira, Anna; Vellalta, Gemma; Carrato, Alfredo; Navarro, Arcadi; Lorente-Galdós, Belén; Silverman, Debra T.; Real, Francisco X.; Wu, Xifeng; Malats, Núria

2013-01-01

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. PMID:24391818

Safety and Tolerability of TAR-200 and Nivolumab in Subjects With Muscle-Invasive Bladder Cancer

ClinicalTrials.gov

2018-05-04

Bladder Cancer TNM Staging Primary Tumor (T) T2; Bladder Cancer TNM Staging Primary Tumor (T) T2A; Bladder Cancer TNM Staging Primary Tumor (T) T2B; Bladder Cancer TNM Staging Primary Tumor (T) T3; Bladder Cancer TNM Staging Primary Tumor (T) T3A; Bladder Cancer TNM Staging Primary Tumor (T) T3B; Bladder Cancer TNM Staging Regional Lymph Node (N) N0; Bladder Cancer TNM Staging Regional Lymph Node (N) N1; Bladder Cancer TNM Staging Distant Metastasis (M) M0

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

PubMed Central

Shih, Cheryl; Porter, Michael P.

2011-01-01

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. PMID:21826139

VEGF Trap in Treating Patients With Recurrent, Locally Advanced, or Metastatic Cancer of the Urothelium

ClinicalTrials.gov

2014-10-10

Adenocarcinoma of the Bladder; Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Squamous Cell Carcinoma of the Bladder; Stage III Bladder Cancer; Stage III Urethral Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer

TCGA Bladder Cancer Study Reveals Potential Drug Targets - TCGA

Cancer.gov

Investigators with the TCGA Research Network have identified new potential therapeutic targets for a major form of bladder cancer, including important genes and pathways that are disrupted in the disease.

Sorafenib in Treating Patients With Regional or Metastatic Cancer of the Urothelium

ClinicalTrials.gov

2014-05-20

Adenocarcinoma of the Bladder; Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Squamous Cell Carcinoma of the Bladder; Stage III Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer

Expression of Epidermal Growth Factor Receptor and Transforming Growth Factor Alpha in Cancer Bladder: Schistosomal and Non-Schistosomal

PubMed Central

Badawy, Afkar A.; El-Hindawi, Ali; Hammam, Olfat; Moussa, Mona; Helal, Noha S.; Kamel, Amira

2017-01-01

Introduction Overexpression of epidermal growth factor receptor (EGFR) has been described in several solid tumors including bladder cancer. Transforming growth factor alpha (TGFα) is frequently deregulated in neoplastic cells and plays a role in the development of bladder cancer. TGFα-EGFR ligand-receptor combination constitutes an important event in multistep tumorigenesis. Methods This study was done on 30 bladder biopsies from patients with urothelial carcinoma, 15 with squamous cell carcinoma, 10 with cystitis and 5 normal control bladder specimens. All were immuohistochemically stained with EGFR and TGFα antibodies. Results EGFR and TGFα were over-expressed in higher grades and late stages of bladder cancer. Moreover, they show higher expression in squamous cell carcinoma compared to urothelial carcinoma and in schistosomal associated lesions than in non-schistosomal associated lesions. Conclusion EGFR and TGFα could be used as prognostic predictors in early stage and grade of bladder cancer cases, especially those with schistosomal association. In addition they can help in selecting patients who can get benefit from anti-EGFR molecular targeted therapy. PMID:28413380

Case report of metastatic invasive breast lobular carcinoma to the urinary bladder.

PubMed

Al Ibraheemi, Ahmed A

2016-01-01

Breast cancer is the most common cancer in women except skin cancer. The common metastatic sites include lymph node, lung, liver and bone. However, metastasis to the bladder is extremely rare. To our knowledge, this is the first case of breast cancer metastasis to urinary bladder in Jordan which is reported. Nine years after the initial diagnosis of lobular breast carcinoma, the patient suffered from left side leg edema; Ultrasonography and Computed tomography scanning showed thickening of posterior bladder wall and bilateral hydronephrosis. The biopsy of the bladder confirmed metastatic lesion from the breast. In contrast to the primary tumor, bladder metastasis showed negative expression of estrogen (ER) and progesterone (PR) receptors. However, Her2neu test was negative in both. The reported case confirms that bladder metastasis from breast cancer tend to occur late after the diagnosis of the primary tumor. Furthermore, bladder metastasis can be asymptomatic and heterogeneous in ER and PR expression in comparison with the primary tumor. This report supports the need for careful follow-up and early intervention whenever such clinical situation is suspected. This report supports further evaluation of receptor status at time of metastasis.

Potential role of melastatin-related transient receptor potential cation channel subfamily M gene expression in the pathogenesis of urinary bladder cancer.

PubMed

Ceylan, Gülay Güleç; Önalan, Ebru Etem; Kuloğlu, Tuncay; Aydoğ, Gülten; Keleş, İbrahim; Tonyali, Şenol; Ceylan, Cavit

2016-12-01

Urinary bladder cancer is one of the most common malignancies of the urinary tract. Ion channels and calcium homeostasis are involved in almost all basic cellular mechanisms. The transient receptor potential cation channel subfamily M (TRPM) takes its name from the melastatin protein, which is classified as potential tumor suppressor. To the best of our knowledge, there have been no previous studies in the literature investigating the role of these ion channels in bladder cancer. The present study aimed to determine whether bladder cancer is associated with mRNA expression levels of TRPM ion channel genes, and whether there is the potential to conduct further studies to establish novel treatment modalities. The present study included a total of 47 subjects, of whom 40 were bladder cancer patients and 7 were controls. Following the histopathological evaluation for bladder carcinoma, the mRNA and protein expression of TRPM were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry in tumor and normal tissues, in order to determine whether there is a difference in the expression of these channels in tumor and normal tissues. Immunoreactivity for TRPM2, TRPM4, TRPM7 and TRPM8 was observed in epithelial bladder cells in the two groups. RT-qPCR revealed a significant increase in TRPM7 expression in bladder cancer tissue compared to the controls (healthy bladder tissue), whereas no differences in TRPM2 or TRPM4 expression levels were observed. There were significant reductions in the expression levels of TRPM5 and TRPM8 in bladder cancer tissues. In the present study, the effects of TRP ion channels on the formation of bladder cancer was investigated. This study is instructive for TRPM2, TRPM4, TRPM5, TRPM7 and TRPM8 and their therapeutic role in bladder cancer. The results support the fact that these gens can be novel targets and can also be tested for during the treatment of bladder cancer.

Trends in the survival of patients diagnosed with kidney or urinary bladder cancer in the Nordic countries 1964-2003 followed up to the end of 2006.

PubMed

Engholm, Gerda; Hakulinen, Timo; Gislum, Mette; Tryggvadóttir, Laufey; Klint, Asa; Bray, Freddie; Storm, Hans H

2010-06-01

Previous studies have shown systematic differences between the Nordic Countries in population-based relative survival following a kidney or urinary bladder cancer diagnosis. Comparison of bladder cancer over time and between Nordic registries is complicated by variable coding practices with respect to the inclusion of in situ cases with invasive tumours. Five-year relative survival of patients with urinary cancer diagnosed in the Nordic countries 1964-2003 and followed up for death through 2006 was studied and contrasted with developments in incidence and mortality. The survival following bladder cancer was higher than for kidney cancer and highest for men. Survival increased over the years in all countries, more for kidney cancer than bladder cancer. For Danish kidney cancer patients, the rate of increase over all the years has been lower than in the other countries, especially among women, resulting in a survival in Denmark some 10-20% points lower than elsewhere in 1999-2003. Danish bladder cancer patient survival was in the last period 4% points lower among men and 10% points lower among women than in the other Nordic countries. The differences were mainly found in the first year following diagnosis, where a higher excess mortality in Denmark was observed. Survival decreased with higher age at diagnosis. The increasing 5-year relative survival in all the Nordic countries for both kidney and bladder cancer are promising, but for kidney cancer a higher percentage detected coincidentally during an imaging investigation for other diseases could play a role. Denmark had the lowest survival, despite their known practice of including benign conditions with invasive bladder cancers. The lower Danish survival after kidney and bladder cancer in the first year after diagnosis could be due to later diagnosis on average, a higher co-morbidity from smoking-related diseases, and perhaps, less adequate cancer treatment and management in Denmark.

Association between cannabis use and the risk of bladder cancer: results from the California Men's Health Study.

PubMed

Thomas, Anil A; Wallner, Lauren P; Quinn, Virginia P; Slezak, Jeffrey; Van Den Eeden, Stephen K; Chien, Gary W; Jacobsen, Steven J

2015-02-01

To investigate the association of cannabis use and tobacco smoking on the incidence of bladder cancer within the California Men's Health Study cohort. We evaluated the records of 84,170 participants in a multiethnic cohort of men aged 45-69 years. Information on demographic and lifestyle factors including smoking history and cannabis use was collected using mailed questionnaires between 2002 and 2003. We linked the study data with clinical records including cancer data from electronic health records. Overall 34,000 (41%) cohort members reported cannabis use, 47,092 (57%) reported tobacco use, 22,500 (27%) reported using both, and 23,467 (29%) used neither. Men were followed over an 11-year period and 279 (0.3%) developed incident bladder tumors. Among cannabis users, 89 (0.3%) developed bladder cancer in comparison to 190 (0.4%) men who did not report cannabis use (P < .001). After adjusting for age, race or ethnicity, and body mass index, using tobacco only was associated with an increased risk of bladder cancer (hazard regression [HR], 1.52; 95% confidence interval [CI], 1.12-2.07), whereas cannabis use only was associated with a 45% reduction in bladder cancer incidence (HR, 0.55; 95% CI, 0.31-1.00). Using both cannabis and tobacco was associated with an HR of 1.28 (95% CI, 0.91-1.80). Although a cause and effect relationship has not been established, cannabis use may be inversely associated with bladder cancer risk in this population. Copyright © 2015 Elsevier Inc. All rights reserved.

Whole-Pelvis or Bladder-Only Chemoradiation for Lymph Node-Negative Invasive Bladder Cancer: Single-Institution Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tunio, Mutahir A., E-mail: drmutahirtonio@hotmail.com; Hashmi, Altaf; Qayyum, Abdul

2012-03-01

Purpose: Whole-pelvis (WP) concurrent chemoradiation (CCRT) is the standard bladder preserving option for patients with invasive bladder cancer. The standard practice is to treat elective pelvic lymph nodes, so our aim was to evaluate whether bladder-only (BO) CCRT leads to results similar to those obtained by standard WP-CCRT. Methods and Materials: Patient eligibility included histopathologically proven muscle-invasive bladder cancer, lymph nodes negative (T2-T4, N-) by radiology, and maximal transurethral resection of bladder tumor with normal hematologic, renal, and liver functions. Between March 2005 and May 2006, 230 patients were accrued. Patients were randomly assigned to WP-CCRT (120 patients) and BO-CCRTmore » (110 patients). Data regarding the toxicity profile, compliance, initial complete response rates at 3 months, and occurrence of locoregional or distant failure were recorded. Results: With a median follow-up time of 5 years (range, 3-6), WP-CCRT was associated with a 5-year disease-free survival of 47.1% compared with 46.9% in patients treated with BO-CCRT (p = 0.5). The bladder preservation rates were 58.9% and 57.1% in WP-CCRT and BO-CCRT, respectively (p = 0.8), and the 5-year overall survival rates were 52.9% for WP-CCRT and 51% for BO-CCRT (p = 0.8). Conclusion: BO-CCRT showed similar rates of bladder preservation, disease-free survival, and overall survival rates as those of WP-CCRT. Smaller field sizes including bladder with 2-cm margins can be used as bladder preservation protocol for patients with muscle-invasive lymph node-negative bladder cancer to minimize the side effects of CCRT.« less

Urinary long noncoding RNAs in nonmuscle-invasive bladder cancer: new architects in cancer prognostic biomarkers.

PubMed

Terracciano, Daniela; Ferro, Matteo; Terreri, Sara; Lucarelli, Giuseppe; D'Elia, Carolina; Musi, Gennaro; de Cobelli, Ottavio; Mirone, Vincenzo; Cimmino, Amelia

2017-06-01

Several reports over the last 10 years provided evidence that long noncoding RNAs (lncRNAs) are often altered in bladder cancers. lncRNAs are longer than 200 nucleotides and function as important regulators of gene expression, interacting with the major pathways of cell growth, proliferation, differentiation, and survival. A large number of lncRNAs has oncogenic function and is more expressed in tumor compared with normal tissues. Their overexpression may be associated with tumor formation, progression, and metastasis in a variety of tumors including bladder cancer. Although lncRNAs have been shown to have critical regulatory roles in cancer biology, the biological functions and prognostic values in nonmuscle-invasive bladder cancer remain largely unknown. Nevertheless, a growing body of evidence suggests that several lncRNAs expression profiles in bladder malignancies are associated with poor prognosis, and they can be detected in biological fluids, such as urines. Here, we review current progress in the biology and the implication of lncRNAs associated with bladder cancer, and we discuss their potential use as diagnosis and prognosis biomarkers in bladder malignancies with a focus on their role in high-risk nonmuscle-invasive tumors. Copyright © 2017 Elsevier Inc. All rights reserved.

MicroRNA-320c inhibits tumorous behaviors of bladder cancer by targeting Cyclin-dependent kinase 6

PubMed Central

2014-01-01

Background Increasing evidence has suggested that dysregulation of microRNAs (miRNAs) could contribute to human disease including cancer. Previous miRNA microarray analysis illustrated that miR-320c is down-regulated in various cancers. However, the roles of miR-320c in human bladder cancer have not been well elucidated. Therefore, this study was performed to investigate the biological functions and molecular mechanisms of miR-320c in human bladder cancer cell lines, discussing whether it could be a therapeutic biomarker of bladder cancer in the future. Methods Two human bladder cancer cell lines and samples from thirteen patients with bladder cancer were analyzed for the expression of miR-320c by quantitative RT-PCR. Over-expression of miR-320c was established by transfecting mimics into T24 and UM-UC-3. Cell proliferation and cell cycle were assessed by cell viability assay, flow cytometry and colony formation assay. Cell motility ability was evaluated by transwell assay. The target gene of miR-320c was determined by luciferase assay, quantitative RT-PCR and western blot. The regulation of cell cycle and mobility by miR-320c was analyzed by western blot. Results We observed that miR-320c was down-regulated in human bladder cancer tissues and bladder cancer cell lines T24 and UM-UC-3. Over-expression of miR-320c could induce G1 phase arrest in UM-UC-3 and T24 cells, and subsequently inhibited cell growth. We also indentified miR-320c could impair UM-UC-3 and T24 cell motility. In addition, we identified CDK6, a cell cycle regulator, as a novel target of miR-320c. Moreover, we demonstrated miR-320c could induce bladder cancer cell cycle arrest and mobility via regulating CDK6. We also observed that inhibition of miR-320c or restoration of CDK6 in miR-320c-over-expressed bladder cancer cells partly reversed the suppressive effects of miR-320c. Conclusions miR-320c could inhibit the proliferation, migration and invasion of bladder cancer cells via regulating CDK6. Our study revealed that miR-320c could be a therapeutic biomarker of bladder cancer in the future. PMID:25178497

Bladder cancer biomarker discovery using global metabolomic profiling of urine.

PubMed

Wittmann, Bryan M; Stirdivant, Steven M; Mitchell, Matthew W; Wulff, Jacob E; McDunn, Jonathan E; Li, Zhen; Dennis-Barrie, Aphrihl; Neri, Bruce P; Milburn, Michael V; Lotan, Yair; Wolfert, Robert L

2014-01-01

Bladder cancer (BCa) is a common malignancy worldwide and has a high probability of recurrence after initial diagnosis and treatment. As a result, recurrent surveillance, primarily involving repeated cystoscopies, is a critical component of post diagnosis patient management. Since cystoscopy is invasive, expensive and a possible deterrent to patient compliance with regular follow-up screening, new non-invasive technologies to aid in the detection of recurrent and/or primary bladder cancer are strongly needed. In this study, mass spectrometry based metabolomics was employed to identify biochemical signatures in human urine that differentiate bladder cancer from non-cancer controls. Over 1000 distinct compounds were measured including 587 named compounds of known chemical identity. Initial biomarker identification was conducted using a 332 subject sample set of retrospective urine samples (cohort 1), which included 66 BCa positive samples. A set of 25 candidate biomarkers was selected based on statistical significance, fold difference and metabolic pathway coverage. The 25 candidate biomarkers were tested against an independent urine sample set (cohort 2) using random forest analysis, with palmitoyl sphingomyelin, lactate, adenosine and succinate providing the strongest predictive power for differentiating cohort 2 cancer from non-cancer urines. Cohort 2 metabolite profiling revealed additional metabolites, including arachidonate, that were higher in cohort 2 cancer vs. non-cancer controls, but were below quantitation limits in the cohort 1 profiling. Metabolites related to lipid metabolism may be especially interesting biomarkers. The results suggest that urine metabolites may provide a much needed non-invasive adjunct diagnostic to cystoscopy for detection of bladder cancer and recurrent disease management.

Bladder preservation in non-metastatic muscle-invasive bladder cancer (MIBC): a single-institution experience

PubMed Central

Gerardi, Marianna A.; Jereczek-Fossa, Barbara A.; Zerini, Dario; Surgo, Alessia; Dicuonzo, Samantha; Spoto, Ruggero; Fodor, Cristiana; Verri, Elena; Rocca, Maria Cossu; Nolè, Franco; Muto, Matteo; Ferro, Matteo; Musi, Gennaro; Bottero, Danilo; Matei, Deliu V.; De Cobelli, Ottavio; Orecchia, Roberto

2016-01-01

The aim of this study is to access the feasibility, toxicity profile, and tumour outcome of an organ preservation curative approach in non-metastatic muscle-invasive bladder cancer. A retrospective analysis was conducted on patients affected by M0 bladder cancer, who refused cystectomy and were treated with a curative approach. The standard bladder preservation scheme included maximal transurethral resection of bladder tumour (TURBT) and combination of radiotherapy and platin-based chemotherapy, followed by endoscopic evaluation, urine cytology, and instrumental evaluation. Thirteen patients fulfilled the inclusion criteria. TNM stage was cT2cN0M0 and cT2cNxM0, in 12 and one patients, respectively. All patients had transitional cell cancer. Twelve patients completed the whole therapeutic programme (a bimodal treatment without chemotherapy for one patient). Median follow-up is 36 months. None of the patients developed severe urinary or intestinal acute toxicity. In 10 patients with a follow-up > 6 months, no cases of severe late toxicity were observed. Response evaluated in 12 patients included complete response and stable disease in 11 patients (92%), and one patient (8%), respectively. At the time of data analysis (March 2016), 10 patients (77%) are alive with no evidence of disease, two patients (15%) died for other reasons, and one patient has suspicious persistent local disease. The trimodality approach, including maximal TURBT, radiotherapy, and chemotherapy for muscle-invasive bladder cancer, is well-tolerated and might be considered a valid and feasible option in fit patients who refuse radical cystectomy. PMID:27563352

Bladder preservation in non-metastatic muscle-invasive bladder cancer (MIBC): a single-institution experience.

PubMed

Gerardi, Marianna A; Jereczek-Fossa, Barbara A; Zerini, Dario; Surgo, Alessia; Dicuonzo, Samantha; Spoto, Ruggero; Fodor, Cristiana; Verri, Elena; Rocca, Maria Cossu; Nolè, Franco; Muto, Matteo; Ferro, Matteo; Musi, Gennaro; Bottero, Danilo; Matei, Deliu V; De Cobelli, Ottavio; Orecchia, Roberto

2016-01-01

The aim of this study is to access the feasibility, toxicity profile, and tumour outcome of an organ preservation curative approach in non-metastatic muscle-invasive bladder cancer. A retrospective analysis was conducted on patients affected by M0 bladder cancer, who refused cystectomy and were treated with a curative approach. The standard bladder preservation scheme included maximal transurethral resection of bladder tumour (TURBT) and combination of radiotherapy and platin-based chemotherapy, followed by endoscopic evaluation, urine cytology, and instrumental evaluation. Thirteen patients fulfilled the inclusion criteria. TNM stage was cT2cN0M0 and cT2cNxM0, in 12 and one patients, respectively. All patients had transitional cell cancer. Twelve patients completed the whole therapeutic programme (a bimodal treatment without chemotherapy for one patient). Median follow-up is 36 months. None of the patients developed severe urinary or intestinal acute toxicity. In 10 patients with a follow-up > 6 months, no cases of severe late toxicity were observed. Response evaluated in 12 patients included complete response and stable disease in 11 patients (92%), and one patient (8%), respectively. At the time of data analysis (March 2016), 10 patients (77%) are alive with no evidence of disease, two patients (15%) died for other reasons, and one patient has suspicious persistent local disease. The trimodality approach, including maximal TURBT, radiotherapy, and chemotherapy for muscle-invasive bladder cancer, is well-tolerated and might be considered a valid and feasible option in fit patients who refuse radical cystectomy.

Arsenic, tobacco smoke, and occupation: associations of multiple agents with lung and bladder cancer.

PubMed

Ferreccio, Catterina; Yuan, Yan; Calle, Jacqueline; Benítez, Hugo; Parra, Roxana L; Acevedo, Johanna; Smith, Allan H; Liaw, Jane; Steinmaus, Craig

2013-11-01

Millions of people worldwide are exposed to arsenic in drinking water, and many are likely coexposed to other agents that could substantially increase their risks of arsenic-related cancer. We performed a case-control study of multiple chemical exposures in 538 lung and bladder cancer cases and 640 controls in northern Chile, an area with formerly high drinking water arsenic concentrations. Detailed information was collected on lifetime arsenic exposure, smoking, secondhand smoke, and other known or suspected carcinogens, including asbestos, silica, and wood dust. Very high lung and bladder cancer odds ratios (ORs), and evidence of greater than additive effects, were seen in people exposed to arsenic concentrations >335 µg/L and who were tobacco smokers (OR = 16, 95% confidence interval = 6.5-40 for lung cancer; and OR = 23 [8.2-66] for bladder cancer; Rothman Synergy Indices = 4.0 [1.7-9.4] and 2.0 [0.92-4.5], respectively). Evidence of greater than additive effects were also seen in people coexposed to arsenic and secondhand tobacco smoke and several other known or suspected carcinogens, including asbestos, silica, and wood dust. These findings suggest that people coexposed to arsenic and other known or suspected carcinogens have very high risks of lung or bladder cancer.

Advances in Imaging in Prostate and Bladder Cancer.

PubMed

Srivastava, Abhishek; Douglass, Laura M; Chernyak, Victoria; Watts, Kara L

2017-09-01

Recent advancements in urologic imaging techniques aim to improve the initial detection of urologic malignancies and subsequent recurrence and to more accurately stage disease. This allows the urologist to make better informed treatment decisions. In particular, exciting advances in the imaging of prostate cancer and bladder cancer have recently emerged including the use of dynamic, functional imaging with MRI and PET. In this review, we will explore these imaging modalities, in addition to new sonography techniques and CT, and how they hope to improve the diagnosis and management of prostate and bladder cancer.

Phase II Pazopanib in Combination With Weekly Paclitaxel in Refractory Urothelial Cancer

ClinicalTrials.gov

2017-05-08

Bladder Cancer; Bladder (Urothelial, Transitional Cell) Cancer; Bladder (Urothelial, Transitional Cell) Cancer Superficial (Non-Invasive); Bladder (Urothelial, Transitional Cell) Cancer Resectable (Pre-Cystectomy); Bladder (Urothelial, Transitional Cell) Cancer Metastatic or Unresectable

Chloroquine and hydroxychloroquine inhibit bladder cancer cell growth by targeting basal autophagy and enhancing apoptosis.

PubMed

Lin, Yi-Chia; Lin, Ji-Fan; Wen, Sheng-I; Yang, Shan-Che; Tsai, Te-Fu; Chen, Hung-En; Chou, Kuang-Yu; Hwang, Thomas I-Sheng

2017-05-01

Chloroquine (CQ) and hydroxychloroquine (HCQ), two antimalarial drugs, are suggested to have potential anticancer properties. in the present study, we investigated the effects of CQ and HCQ on cell growth of bladder cancer with emphasis on autophagy inhibition and apoptosis induction in vitro. The results showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell lines (including RT4, 5637, and T24) in a time- and dose-dependent fashion, especially in advanced bladder cancer cell lines (5637 and T24) compared to immortalized uroepithelial cells (SV-Huc-1) or other reference cancer cell lines (PC3 and MCF-7). We found that 24-hour treatment of CQ or HCQ significantly decreased the clonogenic formation in 5637 and T24 cells compared to SV-Huc-1. As human bladder cancer tumor exhibits high basal level of autophagic activities, we detected the autophagic flux in cells treated with CQ and HCQ, showing an alternation in LC3 flux in CQ- or HCQ-treated cells. Moreover, bladder cancer cells treated with CQ and HCQ underwent apoptosis, resulting in increased caspase 3/7 activities, increased level of cleaved poly(ADP-ribose) polymerase (PARP), caspase 3, and DNA fragmentation. Given these results, targeting autophagy with CQ and HCQ represents an effective cancer therapeutic strategy against human bladder cancer. Copyright © 2017. Published by Elsevier Taiwan.

HPLC assisted Raman spectroscopic studies on bladder cancer

NASA Astrophysics Data System (ADS)

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.

TCGA bladder cancer study reveals potential drug targets

Cancer.gov

Investigators with TCGA have identified new potential therapeutic targets for a major form of bladder cancer, including important genes and pathways that are disrupted in the disease. They also discovered that, at the molecular level, some subtypes of bla

Tissue responses to hexyl 5-aminolevulinate-induced photodynamic treatment in syngeneic orthotopic rat bladder cancer model: possible pathways of action

NASA Astrophysics Data System (ADS)

Arum, Carl-Jørgen; Gederaas, Odrun A.; Larsen, Eivind L. P.; Randeberg, Lise L.; Hjelde, Astrid; Krokan, Hans E.; Svaasand, Lars O.; Chen, Duan; Zhao, Chun-Mei

2011-02-01

Orthotopic bladder cancer model in rats mimics human bladder cancer with respect to urothelial tumorigenesis and progression. Utilizing this model at pT1 (superficial stage), we analyze the tissue responses to hexyl 5-aminolevulinate-induced photodynamic therapy (HAL-PDT). In comparison to untreated rats, HAL-PDT causes little change in tumor-free rat bladder but induces inflammatory changes with increased lymphocytes and mononuclear cell infiltration in rat bladders with tumor. Immunohistochemistry reveals that HAL-PDT is without effect on proliferating cell nuclear antigen expression within the tumor and increases caspase-3 expression in both normal urothelium and the tumor. Transmission electron microscopy reveals severe mitochondrial damage, formations of apoptotic bodies, vacuoles, and lipofuscin bodies, but no microvillus-formed niches in HAL-PDT-treated bladder cancer rats. Bioinformatics analysis of the gene expression profile indicates an activation of T-cell receptor signaling pathway in bladder cancer rats without PDT. HAL-PDT increases the expression of CD3 and CD45RA in the tumor (determined by immunohistochemistry). We suggest that pathways of action of HAL-PDT may include, at least, activations of mitochondrial apoptosis and autophagy, breakdown of cancer stem cell niches, and importantly, enhancement of T-cell activation.

Silibinin inhibits β-catenin/ZEB1 signaling and suppresses bladder cancer metastasis via dual-blocking epithelial-mesenchymal transition and stemness.

PubMed

Wu, Kaijie; Ning, Zhongyun; Zeng, Jin; Fan, Jinhai; Zhou, Jiancheng; Zhang, Tingting; Zhang, Linlin; Chen, Yule; Gao, Yang; Wang, Bin; Guo, Peng; Li, Lei; Wang, Xinyang; He, Dalin

2013-12-01

Muscle-invasive bladder cancer is associated with a high frequency of metastasis, and fewer therapies substantially prolong survival. Silibinin, a nontoxic natural flavonoid, has been shown to exhibit pleiotropic anticancer effects in many cancer types, including bladder cancer. Our and other previous studies have demonstrated that silibinin induced apoptosis and inhibited proliferation of bladder cancer cells, whether silibinin could suppress bladder cancer metastasis has not been elucidated. In the present study, we utilized a novel highly metastatic T24-L cell model, and found that silibinin treatment not only resulted in the suppression of cell migration and invasion in vitro, but also decreased bladder cancer lung metastasis and prolonged animal survival in vivo. Mechanistically, silibinin could inhibit glycogen synthase kinase-3β (GSK3β) phosphorylation, β-catenin nuclear translocation and transactivation, and ZEB1 gene transcription that subsequently regulated the expression of cytokeratins, vimentin and matrix metalloproteinase-2 (MMP2) to reverse epithelial-mesenchymal transition (EMT). On the other hand, silibinin inhibited ZEB1 expression and then suppressed the properties of cancer stem cells (CSCs), which were evidenced as decreased spheroid colony formation, side population, and the expression of stem cell factor CD44. Overall, this study reveals a novel mechanism for silibinin targeting bladder cancer metastasis, in which inactivation of β-catenin/ZEB1 signaling by silibinin leads to dual-block of EMT and stemness. © 2013.

Significance of Random Bladder Biopsies in Non-Muscle Invasive Bladder Cancer

PubMed Central

Kumano, Masafumi; Miyake, Hideaki; Nakano, Yuzo; Fujisawa, Masato

2013-01-01

Background/Aims To evaluate retrospectively the clinical outcome of random bladder biopsies in patients with non-muscle invasive bladder cancer (NMIBC) undergoing transurethral resection (TUR). Patients and Method This study included 234 consecutive patients with NMIBC who underwent random biopsies from normal-appearing urothelium of the bladder, including the anterior wall, posterior wall, right wall, left wall, dome, trigone and/or prostatic urethra, during TUR. Result Thirty-seven patients (15.8%) were diagnosed by random biopsies as having urothelial cancer. Among several factors available prior to TUR, preoperative urinary cytology appeared to be independently related to the detection of urothelial cancer in random biopsies on multivariate analysis. Urinary cytology prior to TUR gave 50.0% sensitivity, 91.7% specificity, 56.8% positive predictive value and 89.3% negative predictive value for predicting the findings of the random biopsies. Conclusion Biopsies of normal-appearing urothelium resulted in the additional detection of urothelial cancer in a definite proportion of NMIBC patients, and it remains difficult to find a reliable alternative to random biopsies. Collectively, these findings suggest that it would be beneficial to perform random biopsies as part of the routine management of NMIBC. PMID:24917759

Ixabepilone in Treating Patients With Advanced Urinary Tract Cancer

ClinicalTrials.gov

2013-01-23

Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer

Bladder cancer and smoking. Part 3: influence of perceptions and beliefs.

PubMed

Anderson, Beverley; Naish, Wendy

This is the third of a four-part series on bladder cancer and smoking. Part one examined the risks factors for bladder cancer, emphasizing that although there are many risk factors, smoking is the main predisposing factor for the disease. Part two presented an overview of bladder cancer, including diagnosis and management of the disease. Part three seeks to determine the extent to which people's concept of what constitutes good health is influenced by their perceptions and beliefs. It then looks at whether educational support, specifically health promotion and health education, are effective in increasing the individual's awareness of the dangers of smoking for their health, and consequently in changing existing behaviours or dissuading them from becoming future smokers.

Mechanisms of Progranulin Action and Regulation in Genitourinary Cancers.

PubMed

Tanimoto, Ryuta; Lu, Kuojung G; Xu, Shi-Qiong; Buraschi, Simone; Belfiore, Antonino; Iozzo, Renato V; Morrione, Andrea

2016-01-01

The growth factor progranulin has emerged in recent years as a critical regulator of transformation in several cancer models, including breast cancer, glioblastomas, leukemias, and hepatocellular carcinomas. Several laboratories, including ours, have also demonstrated an important role of progranulin in several genitourinary cancers, including ovarian, endometrial, cervical, prostate, and bladder tumors, where progranulin acts as an autocrine growth factor thereby modulating motility and invasion of transformed cells. In this review, we will focus on the mechanisms of action and regulation of progranulin signaling in genitourinary cancers with a special emphasis on prostate and bladder tumors.

Mechanisms of Progranulin Action and Regulation in Genitourinary Cancers

PubMed Central

Tanimoto, Ryuta; Lu, Kuojung G.; Xu, Shi-Qiong; Buraschi, Simone; Belfiore, Antonino; Iozzo, Renato V.; Morrione, Andrea

2016-01-01

The growth factor progranulin has emerged in recent years as a critical regulator of transformation in several cancer models, including breast cancer, glioblastomas, leukemias, and hepatocellular carcinomas. Several laboratories, including ours, have also demonstrated an important role of progranulin in several genitourinary cancers, including ovarian, endometrial, cervical, prostate, and bladder tumors, where progranulin acts as an autocrine growth factor thereby modulating motility and invasion of transformed cells. In this review, we will focus on the mechanisms of action and regulation of progranulin signaling in genitourinary cancers with a special emphasis on prostate and bladder tumors. PMID:27512385

Network Biomarkers of Bladder Cancer Based on a Genome-Wide Genetic and Epigenetic Network Derived from Next-Generation Sequencing Data.

PubMed

Li, Cheng-Wei; Chen, Bor-Sen

2016-01-01

Epigenetic and microRNA (miRNA) regulation are associated with carcinogenesis and the development of cancer. By using the available omics data, including those from next-generation sequencing (NGS), genome-wide methylation profiling, candidate integrated genetic and epigenetic network (IGEN) analysis, and drug response genome-wide microarray analysis, we constructed an IGEN system based on three coupling regression models that characterize protein-protein interaction networks (PPINs), gene regulatory networks (GRNs), miRNA regulatory networks (MRNs), and epigenetic regulatory networks (ERNs). By applying system identification method and principal genome-wide network projection (PGNP) to IGEN analysis, we identified the core network biomarkers to investigate bladder carcinogenic mechanisms and design multiple drug combinations for treating bladder cancer with minimal side-effects. The progression of DNA repair and cell proliferation in stage 1 bladder cancer ultimately results not only in the derepression of miR-200a and miR-200b but also in the regulation of the TNF pathway to metastasis-related genes or proteins, cell proliferation, and DNA repair in stage 4 bladder cancer. We designed a multiple drug combination comprising gefitinib, estradiol, yohimbine, and fulvestrant for treating stage 1 bladder cancer with minimal side-effects, and another multiple drug combination comprising gefitinib, estradiol, chlorpromazine, and LY294002 for treating stage 4 bladder cancer with minimal side-effects.

Exposure to polycyclic aromatic hydrocarbons (PAHs) and bladder cancer: evaluation from a gene-environment perspective in a hospital-based case-control study in the Canary Islands (Spain)

PubMed Central

Boada, Luis D; Henríquez-Hernández, Luis A; Navarro, Patricio; Zumbado, Manuel; Almeida-González, Maira; Camacho, María; Álvarez-León, Eva E; Valencia-Santana, Jorge A; Luzardo, Octavio P

2015-01-01

Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been linked to bladder cancer. Objective: To evaluate the role of PAHs in bladder cancer, PAHs serum levels were measured in patients and controls from a case-control study. Methods: A total of 140 bladder cancer patients and 206 healthy controls were included in the study. Sixteen PAHs were analyzed from the serum of subjects by gas chromatography–mass spectrometry. Results: Serum PAHs did not appear to be related to bladder cancer risk, although the profile of contamination by PAHs was different between patients and controls: pyrene (Pyr) was solely detected in controls and chrysene (Chry) was exclusively detected in the cases. Phenanthrene (Phe) serum levels were inversely associated with bladder cancer (OR = 0·79, 95%CI = 0·64–0·99, P = 0·030), although this effect disappeared when the allelic distribution of glutathione-S-transferase polymorphisms of the population was introduced into the model (multinomial logistic regression test, P = 0·933). Smoking (OR = 3·62, 95%CI = 1·93–6·79, P<0·0001) and coffee consumption (OR = 1·73, 95%CI = 1·04–2·86, P = 0·033) were relevant risk factors for bladder cancer. Conclusions: Specific PAH mixtures may play a relevant role in bladder cancer, although such effect seems to be highly modulated by polymorphisms in genes encoding xenobiotic-metabolizing enzymes. PMID:25291984

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

PubMed

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. ©2016 American Association for Cancer Research.

Association between N-Acetyltransferase 2 Polymorphism and Bladder Cancer Risk: a Meta-Analysis in a Single Ethnic Group.

PubMed

Xu, Wan-Jiang; Wen, Li-Ping; Jiang, Xiang-Xin; Ye, Li-Yin; Meng, Fan-Hua; Guan, Sheng; Qian, Ying-Jun; Wei, Jing-Feng

2017-02-01

Many studies have evaluated the correlation between N-acetyltransferase 2 (NAT2) slow acetylation genotype and bladder cancer risk. However, the results are inconsistent and remain to be confirmed in each ethnic group. To assess the effects of NAT2 acetylation status on the risk of bladder cancer in the Chinese population, a meta-analysis was performed. Studies were identified using PubMed and Chinese databases through February 2016. The associations were assessed with pooled odds ratios (ORs) and 95% confidence intervals (CIs). This meta-analysis included 10 studies with 896 bladder cancer cases and 1188 controls. In the overall analysis, NAT2 slow acetylation phenotype was significantly associated with an increased risk of bladder cancer in the Chinese population (OR = 1.68, 95% CI = 1.11 - 2.53). In the subgroup analyses by geographic areas and sources of controls, significant risk was found in Mainland China (OR = 1.83, 95% CI = 1.04 - 3.20) and hospitalbased studies (OR = 1.74, 95% CI = 1.27 - 2.38), but not in Taiwan China. This meta-analysis suggested that the NAT2 slow acetylation genotype is associated with an increased bladder cancer risk in Chinese individuals.

Low Temperature Plasma Kills SCaBER Cancer Cells

NASA Astrophysics Data System (ADS)

Barekzi, Nazir; van Way, Lucas; Laroussi, Mounir

2013-09-01

Squamous cell carcinoma of the bladder is a rare type of bladder cancer that forms as a result of chronic irritation of the epithelial lining of the bladder. The cell line used in this study is SCaBER (ATCC® HTB-3™) derived from squamous cell carcinoma of the human urinary bladder. Current treatments of bladder cancer include surgery, radiation and chemotherapy. However, the cost of these treatments, the potential toxicity of the chemotherapeutic agents and the systemic side-effects warrant an alternative to current cancer treatment. This paper represents preliminary studies to determine the effects of biologically tolerant plasma (BTP) on a cell line of human bladder cancer cells. Previous work by our group using the plasma pencil revealed the efficacy of BTP on leukemia cells suspended in solution. Based on these earlier findings we hypothesized that the plasma exposure would elicit a similar programmed cell death in the SCaBER cells. Trypan blue exclusion and MTT assays revealed the cell killing after exposure to BTP. Our study indicates that low temperature plasma generated by ionizing helium gas and the reactive species may be a suitable and safe alternative for cancer therapy.

Bladder cancer mortality of workers exposed to aromatic amines: a 58-year follow-up.

PubMed

Pira, Enrico; Piolatto, Giorgio; Negri, Eva; Romano, Canzio; Boffetta, Paolo; Lipworth, Loren; McLaughlin, Joseph K; La Vecchia, Carlo

2010-07-21

We previously investigated bladder cancer risk in a cohort of dyestuff workers who were heavily exposed to aromatic amines from 1922 through 1972. We updated the follow-up by 14 years (through 2003) for 590 exposed workers to include more than 30 years of follow-up since last exposure to aromatic amines. Expected numbers of deaths from bladder cancer and other causes were computed by use of national mortality rates from 1951 to 1980 and regional mortality rates subsequently. There were 394 deaths, compared with 262.7 expected (standardized mortality ratio = 1.50, 95% confidence interval = 1.36 to 1.66). Overall, 56 deaths from bladder cancer were observed, compared with 3.4 expected (standardized mortality ratio = 16.5, 95% confidence interval = 12.4 to 21.4). The standardized mortality ratio for bladder cancer increased with younger age at first exposure and increasing duration of exposure. Although the standardized mortality ratio for bladder cancer steadily decreased with time since exposure stopped, the absolute risk remained approximately constant at 3.5 deaths per 1000 man-years up to 29 years after exposure stopped. Excess risk was apparent 30 years or more after last exposure.

Pazopanib in Treating Patients With Metastatic Urothelial Cancer

ClinicalTrials.gov

2014-05-22

Distal Urethral Cancer; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer

Surveillance of nasal and bladder cancer to locate sources of exposure to occupational carcinogens.

PubMed Central

Teschke, K; Morgan, M S; Checkoway, H; Franklin, G; Spinelli, J J; van Belle, G; Weiss, N S

1997-01-01

OBJECTIVE: To locate sources of occupational exposure to nasal and bladder carcinogens for surveillance follow up in British Columbia, Canada. METHODS: Incident cases of nasal cancer (n = 48), bladder cancer (n = 105), and population based controls (n = 159) matched for sex and age, were interviewed about their jobs, exposures, and smoking histories. Odds ratios (ORs) were calculated for 57 occupational groups with stratified exact methods to control for age, sex, and smoking. RESULTS: Occupational groups at increased risk of nasal cancer included: textile workers (six cases, OR 7.6); miners, drillers, and blasters (six cases, OR 3.5); welders (two cases, OR 3.5); pulp and paper workers (three cases, OR 3.1); and plumbers and pipefitters (two cases, OR 3.0). Nasal cancer ORs were not increased in occupations exposed to wood dust, possibly due to low exposures in local wood industries. Strongly increased risks of bladder cancer were found for sheet metal workers (four cases, OR 5.3), miners (19 cases, OR 4.5), gardeners (six cases, OR 3.7), and hairdressers (three cases, OR 3.2). Among occupations originally considered at risk, the following had increased risks of bladder cancer: painters (four cases, OR 2.8); laundry workers (five cases, OR 2.3); chemical and petroleum workers (15 cases, OR 1.8); machinists (eight cases, OR 1.6); and textile workers (three cases, OR 1.5). CONCLUSIONS: Occupational groups with increased risks and three or more cases with similar duties were selected for surveillance follow up. For nasal cancer, these included textile workers (five were garment makers) and pulp and paper workers (three performed maintenance tasks likely to entail stainless steel welding). For bladder cancer, these included miners (12 worked underground), machinists (five worked in traditional machining), hairdressers (three had applied hair dyes), and laundry workers (three were drycleaners). PMID:9245952

Genome-wide interaction study of smoking and bladder cancer risk

PubMed Central

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

Bladder cancer and occupational exposure to diesel and gasoline engine emissions among Canadian men.

PubMed

Latifovic, Lidija; Villeneuve, Paul J; Parent, Marie-Élise; Johnson, Kenneth C; Kachuri, Linda; Harris, Shelley A

2015-12-01

The International Agency for Research on Cancer has classified diesel exhaust as a carcinogen based on lung cancer evidence; however, few studies have investigated the effect of engine emissions on bladder cancer. The purpose of this study was to investigate the association between occupational exposure to diesel and gasoline emissions and bladder cancer in men using data from the Canadian National Enhanced Cancer Surveillance System; a population-based case-control study. This analysis included 658 bladder cancer cases and 1360 controls with information on lifetime occupational histories and a large number of possible cancer risk factors. A job-exposure matrix for engine emissions was supplemented by expert review to assign values for each job across three dimensions of exposure: concentration, frequency, and reliability. Odds ratios (OR) and their corresponding 95% confidence intervals were estimated using logistic regression. Relative to unexposed, men ever exposed to high concentrations of diesel emissions were at an increased risk of bladder cancer (OR = 1.64, 0.87-3.08), but this result was not significant, and those with >10 years of exposure to diesel emissions at high concentrations had a greater than twofold increase in risk (OR = 2.45, 1.04-5.74). Increased risk of bladder cancer was also observed with >30% of work time exposed to gasoline engine emissions (OR = 1.59, 1.04-2.43) relative to the unexposed, but only among men that had never been exposed to diesel emissions. Taken together, our findings support the hypothesis that exposure to high concentrations of diesel engine emissions may increase the risk of bladder cancer. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Clinical significance of CDH13 promoter methylation as a biomarker for bladder cancer: a meta-analysis.

PubMed

Chen, Feng; Huang, Tao; Ren, Yu; Wei, Junjun; Lou, Zhongguan; Wang, Xue; Fan, Xiaoxiao; Chen, Yirun; Weng, Guobin; Yao, Xuping

2016-08-30

Methylation of the tumor suppressor gene H-cadherin (CDH13) has been reported in many cancers. However, the clinical effect of the CDH13 methylation status of patients with bladder cancer remains to be clarified. A systematic literature search was performed to identify eligible studies in the PubMed, Embase, EBSCO, CKNI and Wanfang databases. The pooled odds ratio (OR) and the corresponding 95 % confidence interval (95 % CI) was calculated and summarized. Nine eligible studies were included in the present meta-analysis consisting of a total of 1017 bladder cancer patients and 265 non-tumor controls. A significant association was found between CDH13 methylation levels and bladder cancer (OR = 21.71, P < 0.001). The results of subgroup analyses based on sample type suggested that CDH13 methylation was significantly associated with bladder cancer risk in both the tissue and the urine (OR = 53.94, P < 0.001; OR = 7.71, P < 0.001; respectively). A subgroup analysis based on ethnic population showed that the OR value of methylated CDH13 was higher in Asians than in Caucasians (OR = 35.18, P < 0.001; OR = 8.86, P < 0.001; respectively). The relationships between CDH13 methylation and clinicopathological features were also analyzed. A significant association was not observed between CDH13 methylation status and gender (P = 0.053). Our results revealed that CDH13 methylation was significantly associated with high-grade bladder cancer, multiple bladder cancer and muscle invasive bladder cancer (OR = 2.22, P < 0.001; OR = 1.45, P = 0.032; OR = 3.42, P < 0.001; respectively). Our study indicates that CDH13 methylation may play an important role in the carcinogenesis, development and progression of bladder cancer. In addition, CDH13 methylation has the potential to be a useful biomarker for bladder cancer screening in urine samples and to be a prognostic biomarker in the clinic.

Ultrasound and Biomarker Tests in Predicting Cancer Aggressiveness in Tissue Samples of Patients With Bladder Cancer

ClinicalTrials.gov

2017-06-23

Bladder Papillary Urothelial Carcinoma; Stage 0a Bladder Urothelial Carcinoma; Stage 0is Bladder Urothelial Carcinoma; Stage I Bladder Cancer With Carcinoma In Situ; Stage I Bladder Urothelial Carcinoma; Stage II Bladder Urothelial Carcinoma; Stage III Bladder Urothelial Carcinoma; Stage IV Bladder Urothelial Carcinoma

Quantitative Evaluation of Heavy Metals and Trace Elements in the Urinary Bladder: Comparison Between Cancerous, Adjacent Non-cancerous and Normal Cadaveric Tissue.

PubMed

Abdel-Gawad, Mahmoud; Elsobky, Emad; Shalaby, Mahmoud M; Abd-Elhameed, Mohamed; Abdel-Rahim, Mona; Ali-El-Dein, Bedeir

2016-12-01

The role of heavy metals and trace elements (HMTE) in the development of some cancers has been previously reported. Bladder carcinoma is a frequent malignancy of the urinary tract. The most common risk factors for bladder cancer are exposure to industrial carcinogens, cigarette smoking, gender, and possibly diet. The aim of this study was to evaluate HTME concentrations in the cancerous and adjacent non-cancerous tissues and compare them with those of normal cadaveric bladder. This prospective study included 102 paired samples of full-thickness cancer and adjacent non-cancerous bladder tissues of radical cystectomy (RC) specimens that were histologically proven as invasive bladder cancer (MIBC). We used 17 matched controls of non-malignant bladder tissue samples from cadavers. All samples were processed and evaluated for the concentration of 22 HMTE by using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). Outcome analysis was made by the Mann-Whitney U, chi-square, Kruskal-Wallis, and Wilcoxon signed ranks tests. When compared with cadaveric control or cancerous, the adjacent non-cancerous tissue had higher levels of six elements (arsenic, lead, selenium, strontium, zinc, and aluminum), and when compared with the control alone, it had a higher concentration of calcium, cadmium, chromium, potassium, magnesium, and nickel. The cancerous tissue had a higher concentration of cadmium, lead, chromium, calcium, potassium, phosphorous, magnesium, nickel, selenium, strontium, and zinc than cadaveric control. Boron level was higher in cadaveric control than cancerous and adjacent non-cancerous tissue. Cadmium level was higher in cancerous tissue with node-positive than node-negative cases. The high concentrations of cadmium, lead, chromium, nickel, and zinc, in the cancerous together with arsenic in the adjacent non-cancerous tissues of RC specimens suggest a pathogenic role of these elements in BC. However, further work-up is needed to support this conclusion by the application of these HMTE on BC cell lines.

Sulforaphane for the chemoprevention of bladder cancer: molecular mechanism targeted approach

PubMed Central

Leone, Andrew; Diorio, Gregory; Sexton, Wade; Schell, Michael; Alexandrow, Mark; Fahey, Jed W.; Kumar, Nagi B.

2017-01-01

The clinical course for both early and late stage Bladder Cancer (BC) continues to be characterized by significant patient burden due to numerous occurrences and recurrences requiring frequent surveillance strategies, intravesical drug therapies, and even more aggressive treatments in patients with locally advanced or metastatic disease. For these reasons, BC is also the most expensive cancer to treat. Fortunately, BC offers an excellent platform for chemoprevention interventions with potential to optimize the systemic and local exposure of promising agents to the bladder mucosa. However, other than smoking cessation, there is a paucity of research that systematically examines agents for chemoprevention of bladder cancers. Adopting a systematic, molecular-mechanism based approach, the goal of this review is to summarize epidemiological, in vitro, and preclinical studies, including data regarding the safety, bioavailability, and efficacy of agents evaluated for bladder cancer chemoprevention. Based on the available studies, phytochemicals, specifically isothiocyanates such as sulforaphane, present in Brassicaceae or “cruciferous” vegetables in the precursor form of glucoraphanin are: (a) available in standardized formulations; (b) bioavailable- both systemically and in the bladder; (c) observed to be potent inhibitors of BC carcinogenesis through multiple mechanisms; and (d) without toxicities at these doses. Based on available evidence from epidemiological, in vitro, preclinical, and early phase trials, phytochemicals, specifically isothiocyanates (ITCs) such as sulforaphane (SFN) represent a promising potential chemopreventitive agent in bladder cancer. PMID:28423681

Enzalutamide inhibits androgen receptor-positive bladder cancer cell growth.

PubMed

Kawahara, Takashi; Ide, Hiroki; Kashiwagi, Eiji; El-Shishtawy, Kareem A; Li, Yi; Reis, Leonardo O; Zheng, Yichun; Miyamoto, Hiroshi

2016-10-01

Emerging preclinical evidence suggests that androgen-mediated androgen receptor (AR) signals promote bladder cancer progression. However, little is known about the efficacy of an AR signaling inhibitor, enzalutamide, in the growth of bladder cancer cells. In this study, we compared the effects of enzalutamide and 2 other classic antiandrogens, flutamide and bicalutamide, on androgen-induced bladder cancer cell proliferation, migration, and invasion as well as tumor growth in vivo. Thiazolyl blue cell viability assay, flow cytometry, scratch wound-healing assay, transwell invasion assay, real-time polymerase chain reaction, and reporter gene assay were performed in AR-positive (e.g., UMUC3, TCCSUP, and 647V-AR) and AR-negative (e.g., UMUC3-AR-short hairpin RNA [shRNA], TCCSUP-AR-shRNA, 647V) bladder cancer lines treated with dihydrotestosterone and each AR antagonist. We also used a mouse xenograft model for bladder cancer. Dihydrotestosterone increased bladder cancer cell proliferation, migration, and invasion indicating that endogenous or exogenous AR was functional. Enzalutamide, hydroxyflutamide, and bicalutamide showed similar inhibitory effects, without significant agonist activity, on androgen-mediated cell viability/apoptosis, cell migration, and cell invasion in AR-positive lines. No significant effects of dihydrotestosterone as well as AR antagonists on the growth of AR-negative cells were seen. Correspondingly, in UMUC3 cells, these AR antagonists down-regulated androgen-induced expression of AR, matrix metalloproteinase-2, and interleukin-6. Androgen-enhanced AR-mediated transcriptional activity was also blocked by each AR antagonist exhibiting insignificant agonist activity. In UMUC3 xenograft-bearing mice, oral gavage treatment with each antiandrogen retarded tumor growth, and only enzalutamide demonstrated a statistically significant suppression compared with mock treatment. Our current data support recent observations indicating the involvement of the AR pathway in bladder cancer growth and further suggest that AR antagonists, including enzalutamide, are of therapeutic benefit in AR-positive bladder cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Gene Discovery in Bladder Cancer Progression using cDNA Microarrays

PubMed Central

Sanchez-Carbayo, Marta; Socci, Nicholas D.; Lozano, Juan Jose; Li, Wentian; Charytonowicz, Elizabeth; Belbin, Thomas J.; Prystowsky, Michael B.; Ortiz, Angel R.; Childs, Geoffrey; Cordon-Cardo, Carlos

2003-01-01

To identify gene expression changes along progression of bladder cancer, we compared the expression profiles of early-stage and advanced bladder tumors using cDNA microarrays containing 17,842 known genes and expressed sequence tags. The application of bootstrapping techniques to hierarchical clustering segregated early-stage and invasive transitional carcinomas into two main clusters. Multidimensional analysis confirmed these clusters and more importantly, it separated carcinoma in situ from papillary superficial lesions and subgroups within early-stage and invasive tumors displaying different overall survival. Additionally, it recognized early-stage tumors showing gene profiles similar to invasive disease. Different techniques including standard t-test, single-gene logistic regression, and support vector machine algorithms were applied to identify relevant genes involved in bladder cancer progression. Cytokeratin 20, neuropilin-2, p21, and p33ING1 were selected among the top ranked molecular targets differentially expressed and validated by immunohistochemistry using tissue microarrays (n = 173). Their expression patterns were significantly associated with pathological stage, tumor grade, and altered retinoblastoma (RB) expression. Moreover, p33ING1 expression levels were significantly associated with overall survival. Analysis of the annotation of the most significant genes revealed the relevance of critical genes and pathways during bladder cancer progression, including the overexpression of oncogenic genes such as DEK in superficial tumors or immune response genes such as Cd86 antigen in invasive disease. Gene profiling successfully classified bladder tumors based on their progression and clinical outcome. The present study has identified molecular biomarkers of potential clinical significance and critical molecular targets associated with bladder cancer progression. PMID:12875971

Association Between N-acetyltransferase 2 Polymorphism and Bladder Cancer Risk: Results From Studies of the Past Decade and a Meta-Analysis.

PubMed

Wu, Haoran; Wang, Xugang; Zhang, Liang; Mo, Naixin; Lv, Zhong

2016-04-01

Numerous studies have identified that the slow acetylation status of N-acetyltransferase 2 (NAT2) is associated with an elevated bladder cancer risk. However, the results remain inconclusive. The aim of our study was to evaluate the effect of NAT2 acetylation status in patients with bladder cancer. Electronic databases were searched to retrieve related studies published in the past decade. The pooled odds ratio (OR) with its 95% confidence interval (CI) was used to calculate the strength of this relationship. Overall, a total of 18 studies were selected for the analysis, which included 4473 bladder cancer cases and 7204 matched controls. Our result showed that the NAT2 slow acetylation phenotypes were significantly associated with an increased risk of bladder cancer compared with the rapid phenotypes (OR, 1.56; 95% CI, 1.33-1.82; P < .00001) in a random-effect model. This significant association was also found in a subgroup analysis of ethnicity (P < .05). Furthermore, the NAT2 slow phenotypes also significantly increased the risk of bladder cancer in smokers (OR, 0.75; 95% CI, 0.62-0.90; P = .002). However, no correlation was found between the combined effect of NAT2 slow phenotypes and gender with bladder cancer risk (OR, 0.89; 95% CI, 0.28-2.78; P = .84). In conclusion, our results suggest that the NAT2 slow acetylator, in particular, the NAT2 slow acetylator combined with smoking, are associated with an increased bladder cancer risk. Future well-designed studies with large populations and more ethnicities are needed to clarify this association further. Copyright © 2016 Elsevier Inc. All rights reserved.

Artificial sweeteners and absence of bladder cancer risk in Copenhagen.

PubMed

Møller-Jensen, O; Knudsen, J B; Sørensen, B L; Clemmesen, J

1983-11-15

During the years 1979 to 1981 a population-based case-control study of bladder cancer including papillomas was performed in Greater Copenhagen. After exclusions some 388 patients (290 males; 98 females) and an age- and sex-matched group of 787 controls (592 males; 195 females) remained for analysis. Controls were selected at random from the general population of the study area. All persons were interviewed concerning use of artificial sweeteners in addition to their exposure to a number of other known or suspected risk factors for bladder cancer. Fifty-five male bladder cancer patients (19.4%) and 150 controls (25.7%) had at some time used artificial sweeteners regularly. Among females 27.1% of cases and 25.9% of controls regularly used sweeteners. In neither sex was the relative risk significantly increased in users compared with non-users of artificial sweeteners. The relative risk of 0.78 in the two sexes combined was not significantly different from 1.0 (95% C.I.: 0.58-1.05). There was no indication of a regular increase in risk with increasing daily consumption of table-top sweeteners nor was there any indication of an increase in risk with a duration of regular use of artificial sweeteners. Taking into account a possible latency period between first regular use and bladder cancer development did not change the finding of an absence of association between use of artificial sweeteners and the risk of bladder cancer. Neither saccharine nor cyclamate users had an increased risk of bladder cancer. This population-based case-control investigation provides further evidence that it is highly unlikely that the consumption of artificial sweeteners has contributed to current bladder cancer rates in man.

sEphB4-HSA Before Surgery in Treating Patients With Bladder Cancer, Prostate Cancer, or Kidney Cancer

ClinicalTrials.gov

2018-06-08

Infiltrating Bladder Urothelial Carcinoma; Recurrent Bladder Carcinoma; Stage I Prostate Cancer; Stage I Renal Cell Cancer; Stage II Bladder Urothelial Carcinoma; Stage II Renal Cell Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer

Modeling bladder cancer in mice: opportunities and challenges

PubMed Central

Kobayashi, Takashi; Owczarek, Tomasz B.; McKiernan, James M.; Abate-Shen, Cory

2015-01-01

The prognosis and treatment of bladder cancer have hardly improved in the last 20 years. Bladder cancer remains a debilitating and often fatal disease, and among the most costly cancers to treat. The generation of informative mouse models has the potential to improve our understanding of bladder cancer progression, as well as impact its diagnosis and treatment. However, relatively few mouse models of bladder cancer have been described and particularly few that develop invasive cancer phenotypes. This review focuses on opportunities for improving the landscape of mouse models of bladder cancer. PMID:25533675

Bladder cancer screening in aluminum smelter workers.

PubMed

Taiwo, Oyebode A; Slade, Martin D; Cantley, Linda F; Tessier-Sherman, Baylah; Galusha, Deron; Kirsche, Sharon R; Donoghue, A Michael; Cullen, Mark R

2015-04-01

To present results of a bladder cancer screening program conducted in 18 aluminum smelters in the United States from January 2000 to December 2010. Data were collected on a cohort of workers with a history of working in coal tar pitch volatile exposed areas including urine analysis for conventional cytology and ImmunoCyt/uCyt+ assay. ImmunoCyt/uCyt+ and cytology in combination showed a sensitivity of 62.30%, a specificity of 92.60%, a negative predictive value of 99.90%, and a positive predictive value of 2.96%. Fourteen cases of bladder cancer were detected, and the standardized incidence ratio of bladder cancer was 1.18 (95% confidence interval, 0.65 to 1.99). Individuals who tested positive on either test who were later determined to be cancer free had undergone expensive and invasive tests. Evidence to support continued surveillance of this cohort has not been demonstrated.

Bladder Cancer Screening in Aluminum Smelter Workers

PubMed Central

Taiwo, Oyebode A.; Slade, Martin D.; Cantley, Linda F.; Tessier-Sherman, Baylah; Galusha, Deron; Kirsche, Sharon R.; Donoghue, A. Michael

2015-01-01

Objective: To present results of a bladder cancer screening program conducted in 18 aluminum smelters in the United States from January 2000 to December 2010. Methods: Data were collected on a cohort of workers with a history of working in coal tar pitch volatile exposed areas including urine analysis for conventional cytology and ImmunoCyt/uCyt+ assay. Results: ImmunoCyt/uCyt+ and cytology in combination showed a sensitivity of 62.30%, a specificity of 92.60%, a negative predictive value of 99.90%, and a positive predictive value of 2.96%. Fourteen cases of bladder cancer were detected, and the standardized incidence ratio of bladder cancer was 1.18 (95% confidence interval, 0.65 to 1.99). Individuals who tested positive on either test who were later determined to be cancer free had undergone expensive and invasive tests. Conclusions: Evidence to support continued surveillance of this cohort has not been demonstrated. PMID:25525927

Afatinib in Advanced Refractory Urothelial Cancer

ClinicalTrials.gov

2017-09-28

Distal Urethral Cancer; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Urethral Cancer; Stage III Bladder Cancer; Stage III Urethral Cancer; Stage IV Bladder Cancer; Stage IV Urethral Cancer; Ureter Cancer

Bladder Cancer—Patient Version

Cancer.gov

The most common type of bladder cancer is transitional cell carcinoma, also called urothelial carcinoma. Smoking is a major risk factor for bladder cancer. Bladder cancer is often diagnosed at an early stage. Start here to find information on bladder cancer treatment, screening, research, and statistics.

Trastuzumab in Treating Patients With Previously Treated, Locally Advanced, or Metastatic Cancer of the Urothelium

ClinicalTrials.gov

2013-05-01

Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer

Gemcitabine Hydrochloride and Cisplatin or High-Dose Methotrexate, Vinblastine, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Urothelial Cancer

ClinicalTrials.gov

2014-01-27

Anterior Urethral Cancer; Localized Transitional Cell Cancer of the Renal Pelvis and Ureter; Posterior Urethral Cancer; Recurrent Bladder Cancer; Recurrent Urethral Cancer; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Ureter Cancer; Urethral Cancer Associated With Invasive Bladder Cancer

The economics of bladder cancer: costs and considerations of caring for this disease.

PubMed

Svatek, Robert S; Hollenbeck, Brent K; Holmäng, Sten; Lee, Richard; Kim, Simon P; Stenzl, Arnulf; Lotan, Yair

2014-08-01

Due to high recurrence rates, intensive surveillance strategies, and expensive treatment costs, the management of bladder cancer contributes significantly to medical costs. To provide a concise evaluation of contemporary cost-related challenges in the care of patients with bladder cancer. An emphasis is placed on the initial diagnosis of bladder cancer and therapy considerations for both non-muscle-invasive bladder cancer (NMIBC) and more advanced disease. A systematic review of the literature was performed using Medline (1966 to February 2011). Medical Subject Headings (MeSH) terms for search criteria included "bladder cancer, neoplasms" OR "carcinoma, transitional cell" AND all cost-related MeSH search terms. Studies evaluating the costs associated with of various diagnostic or treatment approaches were reviewed. Routine use of perioperative chemotherapy following complete transurethral resection of bladder tumor has been estimated to provide a cost savings. Routine office-based fulguration of small low-grade recurrences could decrease costs. Another potential important target for decreasing variation and cost lies in risk-modified surveillance strategies after initial bladder tumor removal to reduce the cost associated with frequent cystoscopic and radiographic procedures. Optimizing postoperative care after radical cystectomy has the potential to decrease length of stay and perioperative morbidity with substantial decreases in perioperative care expenses. The gemcitabine-cisplatin regimen has been estimated to result in a modest increase in cost effectiveness over methotrexate, vinblastine, doxorubicin, and cisplatin. Additional costs of therapies need to be balanced with effectiveness, and there are significant gaps in knowledge regarding optimal surveillance and treatment of both early and advanced bladder cancer. Regardless of disease severity, improvements in the efficiency of bladder cancer care to limit unnecessary interventions and optimize effective cancer treatment can reduce overall health care costs. Two scenarios where economic and comparative-effectiveness research is limited but would be most beneficial are (1) the management of NMIBC patients where excessive costs are due to vigilant surveillance strategies and (2) in patients with metastatic disease due to the enormous cost associated with late-stage and end-of-life care. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Improving bladder cancer patient care: a pharmacoeconomic perspective.

PubMed

Gore, John L; Gilbert, Scott M

2013-06-01

Bladder cancer is the most expensive cancer per capita to treat in the US healthcare system. Substantial costs associated with the diagnosis, management and surveillance of bladder cancer account for the bulk of the expense; yet, for that cost, patients may not receive high-quality care. Herein the authors review the sources of expenditure associated with bladder cancer care, review population-level analyses of the quality of bladder cancer care in the USA, and discuss opportunities for quality improvement that may yield greater value for men and women newly diagnosed with bladder cancer.

An etiologic prediction model incorporating biomarkers to predict the bladder cancer risk associated with occupational exposure to aromatic amines: a pilot study.

PubMed

Mastrangelo, Giuseppe; Carta, Angela; Arici, Cecilia; Pavanello, Sofia; Porru, Stefano

2017-01-01

No etiological prediction model incorporating biomarkers is available to predict bladder cancer risk associated with occupational exposure to aromatic amines. Cases were 199 bladder cancer patients. Clinical, laboratory and genetic data were predictors in logistic regression models (full and short) in which the dependent variable was 1 for 15 patients with aromatic amines related bladder cancer and 0 otherwise. The receiver operating characteristics approach was adopted; the area under the curve was used to evaluate discriminatory ability of models. Area under the curve was 0.93 for the full model (including age, smoking and coffee habits, DNA adducts, 12 genotypes) and 0.86 for the short model (including smoking, DNA adducts, 3 genotypes). Using the "best cut-off" of predicted probability of a positive outcome, percentage of cases correctly classified was 92% (full model) against 75% (short model). Cancers classified as "positive outcome" are those to be referred for evaluation by an occupational physician for etiological diagnosis; these patients were 28 (full model) or 60 (short model). Using 3 genotypes instead of 12 can double the number of patients with suspect of aromatic amine related cancer, thus increasing costs of etiologic appraisal. Integrating clinical, laboratory and genetic factors, we developed the first etiologic prediction model for aromatic amine related bladder cancer. Discriminatory ability was excellent, particularly for the full model, allowing individualized predictions. Validation of our model in external populations is essential for practical use in the clinical setting.

Vitamin K2 Induces Mitochondria-Related Apoptosis in Human Bladder Cancer Cells via ROS and JNK/p38 MAPK Signal Pathways

PubMed Central

Duan, Fengsen; Yu, Yuejin; Guan, Rijian; Xu, Zhiliang; Liang, Huageng; Hong, Ling

2016-01-01

The effects of vitamin K2 on apoptosis in a variety of cancer cells have been well established in previous studies. However, the apoptotic effect of vitamin K2 on bladder cancer cells has not been evaluated. The aim of this study is to examine the apoptotic activity of Vitamin K2 in bladder cancer cells and investigate the underlying mechanism. In this study, Vitamin K2 induced apoptosis in bladder cancer cells through mitochondria pathway including loss of mitochondria membrane potential, cytochrome C release and caspase-3 cascade. Furthermore, the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK was detected in Vitamin K2-treated cells and both SP600125 (an inhibitor of JNK) and SB203580 (an inhibitor of p38 MAPK) completely abolished the Vitamin K2-induced apoptosis and loss of mitochondria membrane potential. Moreover, the generation of reactive oxygen species (ROS) was detected in bladder cancer cells, upon treatment of vitamin K2 and the anti-oxidant N-acetyl cysteine (NAC) almost blocked the Vitamin K2-triggered apoptosis, loss of mitochondria membrane potential and activation of JNK and p38 MAPK. Taken together, these findings revealed that Vitamin K2 induces apoptosis in bladder cancer cells via ROS-mediated JNK/p38 MAPK and Mitochondrial pathways. PMID:27570977

Vitamin K2 Induces Mitochondria-Related Apoptosis in Human Bladder Cancer Cells via ROS and JNK/p38 MAPK Signal Pathways.

PubMed

Duan, Fengsen; Yu, Yuejin; Guan, Rijian; Xu, Zhiliang; Liang, Huageng; Hong, Ling

2016-01-01

The effects of vitamin K2 on apoptosis in a variety of cancer cells have been well established in previous studies. However, the apoptotic effect of vitamin K2 on bladder cancer cells has not been evaluated. The aim of this study is to examine the apoptotic activity of Vitamin K2 in bladder cancer cells and investigate the underlying mechanism. In this study, Vitamin K2 induced apoptosis in bladder cancer cells through mitochondria pathway including loss of mitochondria membrane potential, cytochrome C release and caspase-3 cascade. Furthermore, the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK was detected in Vitamin K2-treated cells and both SP600125 (an inhibitor of JNK) and SB203580 (an inhibitor of p38 MAPK) completely abolished the Vitamin K2-induced apoptosis and loss of mitochondria membrane potential. Moreover, the generation of reactive oxygen species (ROS) was detected in bladder cancer cells, upon treatment of vitamin K2 and the anti-oxidant N-acetyl cysteine (NAC) almost blocked the Vitamin K2-triggered apoptosis, loss of mitochondria membrane potential and activation of JNK and p38 MAPK. Taken together, these findings revealed that Vitamin K2 induces apoptosis in bladder cancer cells via ROS-mediated JNK/p38 MAPK and Mitochondrial pathways.

Profiling the Urinary Microbiota in Male Patients With Bladder Cancer in China

PubMed Central

Wu, Peng; Zhang, Guihao; Zhao, Jie; Chen, Jiawei; Chen, Yang; Huang, Weina; Zhong, Jialei; Zeng, Jiarong

2018-01-01

Mounting evidence indicates that microbiome plays an important role in the development and progression of cancer. The dogma that urine in healthy individuals must be sterile has been overturned. Dysbiosis of the urinary microbiome has been revealed responsible for various urological disorders, including prostate cancer. The link between chronic inflammation, microbiome and solid tumors has been established for various neoplastic diseases. However, a detailed and comprehensive analysis of urinary microenvironment of bladder cancer has not been yet reported. We performed this study to characterize the potential urinary microbial community possibly associated with bladder cancer. Mid-stream urine was collected from 31 male patients with bladder cancer and 18 non-neoplastic controls. DNA was extracted from urine pellet samples and processed for high throughput 16S rRNA amplicon sequencing of the V4 region using Illumina MiSeq. Sequencing reads were filtered using QIIME and clustered using UPARSE. We observed increased bacterial richness (Observed Species, Chao 1 and Ace indexes; cancer vs. control; 120.0 vs. 56.0; 134.5 vs. 68.3; and 139.6 vs. 72.9, respectively), enrichment of some bacterial genera (e.g., Acinetobacter, Anaerococcus, and Sphingobacterium) and decrease of some bacterial genera (e.g., Serratia, Proteus, and Roseomonas) in cancer group when compared to non-cancer group. Significant difference in beta diversity was found between cancer and non-cancer group, among different risk level, but not among different tumor grade. Enrichment of Herbaspirillum, Porphyrobacter, and Bacteroides was observed in cancer patients with high risk of recurrence and progression, which means these genera maybe potential biomarkers for risk stratification. The PICRUSt showed that various functional pathways were enriched in cancer group, including Staphylococcus aureus infection, glycerolipid metabolism and retinol metabolism. To our knowledge, we performed the most comprehensive study to date to characterize the urinary microbiome associated with bladder cancer. A better understanding of the role of microbiome in the development and progression of bladder cancer could pave a new way for exploring new therapeutic options and biomarkers. PMID:29904624

Profiling the Urinary Microbiota in Male Patients With Bladder Cancer in China.

PubMed

Wu, Peng; Zhang, Guihao; Zhao, Jie; Chen, Jiawei; Chen, Yang; Huang, Weina; Zhong, Jialei; Zeng, Jiarong

2018-01-01

Mounting evidence indicates that microbiome plays an important role in the development and progression of cancer. The dogma that urine in healthy individuals must be sterile has been overturned. Dysbiosis of the urinary microbiome has been revealed responsible for various urological disorders, including prostate cancer. The link between chronic inflammation, microbiome and solid tumors has been established for various neoplastic diseases. However, a detailed and comprehensive analysis of urinary microenvironment of bladder cancer has not been yet reported. We performed this study to characterize the potential urinary microbial community possibly associated with bladder cancer. Mid-stream urine was collected from 31 male patients with bladder cancer and 18 non-neoplastic controls. DNA was extracted from urine pellet samples and processed for high throughput 16S rRNA amplicon sequencing of the V4 region using Illumina MiSeq. Sequencing reads were filtered using QIIME and clustered using UPARSE. We observed increased bacterial richness (Observed Species, Chao 1 and Ace indexes; cancer vs. control; 120.0 vs. 56.0; 134.5 vs. 68.3; and 139.6 vs. 72.9, respectively), enrichment of some bacterial genera (e.g., Acinetobacter, Anaerococcus, and Sphingobacterium ) and decrease of some bacterial genera (e.g., Serratia, Proteus , and Roseomonas ) in cancer group when compared to non-cancer group. Significant difference in beta diversity was found between cancer and non-cancer group, among different risk level, but not among different tumor grade. Enrichment of Herbaspirillum, Porphyrobacter , and Bacteroides was observed in cancer patients with high risk of recurrence and progression, which means these genera maybe potential biomarkers for risk stratification. The PICRUSt showed that various functional pathways were enriched in cancer group, including Staphylococcus aureus infection, glycerolipid metabolism and retinol metabolism. To our knowledge, we performed the most comprehensive study to date to characterize the urinary microbiome associated with bladder cancer. A better understanding of the role of microbiome in the development and progression of bladder cancer could pave a new way for exploring new therapeutic options and biomarkers.

Effects of increased Kindlin-2 expression in bladder cancer stromal fibroblasts.

PubMed

Wu, Jitao; Yu, Cuicui; Cai, Li; Lu, Youyi; Jiang, Lei; Liu, Chu; Li, Yongwei; Feng, Fan; Gao, Zhenli; Zhu, Zhe; Yu, Shengqiang; Yuan, Hejia; Cui, Yuanshan

2017-08-01

Kindlin-2 is a focal adhesion protein highly expressed in bladder cancer stromal fibroblasts. We investigated the prognostic significance of Kindlin-2 in bladder cancer stromal fibroblasts and evaluated the effects of Kindlin-2 on the malignant behaviors of tumor cells. Immunohistochemical staining of 203 paraffin-embedded bladder cancer tissues showed that Kindlin-2 expression correlated with advanced stage, high grade, and relapse of bladder cancer. Kaplan-Meier survival analysis demonstrated that patients exhibiting high Kindlin-2 expression had shorter survival times than those with low Kindlin-2 expression ( p < 0.01). Multivariate analysis revealed that high Kindlin-2 expression leads to poor prognosis in bladder cancer. Using cancer-associated fibroblasts (CAFs) isolated from human bladder cancer tissue, we observed that Kindlin-2 knockdown decreased CAFs activation, resulting in decreased expression of α-smooth muscle actin (α-SMA) and the extracellular matrix protein fibronectin. Kindlin-2 suppression also reduced CAF-induced bladder cancer cell migration and invasion. Moreover, we found that Kindlin-2 activates CAFs and promotes the invasiveness of bladder cancer cells by stimulating TGF-β-induced epithelial-mesenchymal transition. These results support targeting Kindlin-2 and the corresponding activated CAFs in bladder cancer therapy.

Enzalutamide inhibits proliferation of gemcitabine-resistant bladder cancer cells with increased androgen receptor expression.

PubMed

Kameyama, Koji; Horie, Kengo; Mizutani, Kosuke; Kato, Taku; Fujita, Yasunori; Kawakami, Kyojiro; Kojima, Toshio; Miyazaki, Tatsuhiko; Deguchi, Takashi; Ito, Masafumi

2017-01-01

Advanced bladder cancer is treated mainly with gemcitabine and cisplatin, but most patients eventually become resistance. Androgen receptor (AR) signaling has been implicated in bladder cancer as well as other types of cancer including prostate cancer. In this study, we investigated the expression and role of AR in gemcitabine-resistant bladder cancer cells and also the potential of enzalutamide, an AR inhibitor, as a therapeutic for the chemoresistance. First of all, we established gemcitabine-resistant T24 cells (T24GR) from T24 bladder cancer cells and performed gene expression profiling. Microarray analysis revealed upregulation of AR expression in T24GR cells compared with T24 cells. AR mRNA and protein expression was confirmed to be increased in T24GR cells, respectively, by quantitative RT-PCR and western blot analysis, which was associated with more potent AR transcriptional activity as measured by luciferase reporter assay. The copy number of AR gene in T24GR cells determined by PCR was twice as many as that of T24 cells. AR silencing by siRNA transfection resulted in inhibition of proliferation of T24GR cells. Cell culture in charcoal-stripped serum and treatment with enzalutamide inhibited growth of T24GR cells, which was accompanied by cell cycle arrest. AR transcriptional activity was found to be reduced in T24GR cells by enzalutamide treatment. Lastly, enzalutamide also inhibited cell proliferation of HTB5 bladder cancer cells that express AR and possess intrinsic resistance to gemcitabine. Our results suggest that enzalutamide may have the potential to treat patients with advanced gemcitabine-resistant bladder cancer with increased AR expression.

Bladder cancer exosomes contain EDIL-3/Del1 and facilitate cancer progression.

PubMed

Beckham, Carla J; Olsen, Jayme; Yin, Peng-Nien; Wu, Chia-Hao; Ting, Huei-Ju; Hagen, Fred K; Scosyrev, Emelian; Messing, Edward M; Lee, Yi-Fen

2014-08-01

High grade bladder cancer is an extremely aggressive malignancy associated with high rates of morbidity and mortality. Understanding how exosomes may affect bladder cancer progression could reveal novel therapeutic targets. Exosomes derived from human bladder cancer cell lines and the urine of patients with high grade bladder cancer were assessed for the ability to promote cancer progression in standard assays. Exosomes purified from the high grade bladder cancer cell line TCC-SUP and the nonmalignant urothelial cell line SV-HUC were submitted for mass spectrometry analysis. EDIL-3 was identified and selected for further analysis. Western blot was done to determine EDIL-3 levels in urinary exosomes from patients with high grade bladder cancer. shRNA gene knockdown and recombinant EDIL-3 were applied to study EDIL-3 function. Exosomes isolated from high grade bladder cancer cells and the urine of patients with high grade bladder cancer promoted angiogenesis and migration of bladder cancer cells and endothelial cells. We silenced EDIL-3 expression and found that shEDIL-3 exosomes did not facilitate angiogenesis, and urothelial and endothelial cell migration. Moreover, exosomes purified from the urine of patients with high grade bladder cancer contained significantly higher EDIL-3 levels than exosomes from the urine of healthy controls. EDIL-3 activated epidermal growth factor receptor signaling while blockade of epidermal growth factor receptor signaling abrogated this EDIL-3 induced bladder cell migration. Exosomes derived from the urine of patients with bladder cancer contains bioactive molecules such as EDIL-3. Identifying these components and their associated oncogenic pathways could lead to novel therapeutic targets and treatment strategies. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Quality of Life in Non-Muscle-Invasive Bladder Cancer Survivors: A Systematic Review.

PubMed

Jung, Ahrang; Nielsen, Matthew E; Crandell, Jamie L; Palmer, Mary H; Bryant, Ashley Leak; Smith, Sophia K; Mayer, Deborah K

2018-06-01

Non-muscle-invasive bladder cancer (NMIBC) represents approximately 75% of newly diagnosed patients with bladder cancer. Non-muscle-invasive bladder cancer survivors have unique chronic burdens including frequent recurrences, repeated surveillance cystoscopies and treatments, and the highest lifetime medical cost per person among all cancers. The purpose of this study was to summarize studies assessing quality of life (QOL) in NMIBC survivors. The literature from January 2005 to March 2017 found in PubMed, CINAHL, and PsycINFO databases was reviewed systematically. Inclusion criteria were as follows: (1) research about NMIBC survivors, (2) outcomes included QOL, (3) original research article published in peer-reviewed journals, and (4) published in English. A total of 15 studies were included: 14 quantitative studies and 1 mixed-methods study. Non-muscle-invasive bladder cancer survivors had significantly lower QOL compared with the general population, especially in fatigue, physical and role functioning, and mental health. Repeated transurethral resections and intravesical treatments were associated with impaired physical function and mental health. Most NMIBC survivors had concerns of urinary and bowel problems and sexual function. Despite a good prognosis, NMIBC and its treatment have a significant impact on QOL in survivors. The findings showed large burdens in NMIBC survivors and suggest that further research is needed to better understand potential opportunities to improve QOL in this population. Oncology nurses are in the critical position for assessing symptoms and concerns. Oncology nurses should pay special attention to NMIBC survivors who have unique symptoms and burden with the aim of improving survivors' QOL.

Pathobiology and Chemoprevention of Bladder Cancer

PubMed Central

Tanaka, Takuji; Miyazawa, Katsuhito; Tsukamoto, Tetsuya; Kuno, Toshiya; Suzuki, Koji

2011-01-01

Our understanding of the pathogenesis of bladder cancer has improved considerably over the past decade. Translating these novel pathobiological discoveries into therapies, prevention, or strategies to manage patients who are suspected to have or who have been diagnosed with bladder cancer is the ultimate goal. In particular, the chemoprevention of bladder cancer development is important, since urothelial cancer frequently recurs, even if the primary cancer is completely removed. The numerous alterations of both oncogenes and tumor suppressor genes that have been implicated in bladder carcinogenesis represent novel targets for therapy and prevention. In addition, knowledge about these genetic alterations will help provide a better understanding of the biological significance of preneoplastic lesions of bladder cancer. Animal models for investigating bladder cancer development and prevention can also be developed based on these alterations. This paper summarizes the results of recent preclinical and clinical chemoprevention studies and discusses screening for bladder cancer. PMID:21941546

Nomograms Predicting Response to Therapy and Outcomes After Bladder-Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coen, John J., E-mail: jcoen@harthosp.org; Paly, Jonathan J.; Niemierko, Andrzej

2013-06-01

Purpose: Selective bladder preservation by use of trimodality therapy is an established management strategy for muscle-invasive bladder cancer. Individual disease features have been associated with response to therapy, likelihood of bladder preservation, and disease-free survival. We developed prognostic nomograms to predict the complete response rate, disease-specific survival, and likelihood of remaining free of recurrent bladder cancer or cystectomy. Methods and Materials: From 1986 to 2009, 325 patients were managed with selective bladder preservation at Massachusetts General Hospital (MGH) and had complete data adequate for nomogram development. Treatment consisted of a transurethral resection of bladder tumor followed by split-course chemoradiation. Patientsmore » with a complete response at midtreatment cystoscopic assessment completed radiation, whereas those with a lesser response underwent a prompt cystectomy. Prognostic nomograms were constructed predicting complete response (CR), disease-specific survival (DSS), and bladder-intact disease-free survival (BI-DFS). BI-DFS was defined as the absence of local invasive or regional recurrence, distant metastasis, bladder cancer-related death, or radical cystectomy. Results: The final nomograms included information on clinical T stage, presence of hydronephrosis, whether a visibly complete transurethral resection of bladder tumor was performed, age, sex, and tumor grade. The predictive accuracy of these nomograms was assessed. For complete response, the area under the receiving operating characteristic curve was 0.69. The Harrell concordance index was 0.61 for both DSS and BI-DFS. Conclusions: Our nomograms allow individualized estimates of complete response, DSS, and BI-DFS. They may assist patients and clinicians making important treatment decisions.« less

Sorafenib in Treating Patients With Advanced or Metastatic Cancer of the Urinary Tract

ClinicalTrials.gov

2015-08-04

Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder

Phase II Trial Of PS-341 (Bortezomib) In Patients With Previously Treated Advanced Urothelial Tract Transitional Cell Carcinoma

ClinicalTrials.gov

2013-06-04

Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Stage III Bladder Cancer; Stage III Urethral Cancer; Stage IV Bladder Cancer; Stage IV Urethral Cancer; Transitional Cell Carcinoma of the Bladder; Ureter Cancer

Severity of hydronephrosis correlates with tumour invasiveness and urinary bladder recurrence of ureteric cancer.

PubMed

Luo, Hao Lun; Kang, Chih Hsiung; Chen, Yen Ta; Chuang, Yao Chi; Lee, Wei Ching; Cheng, Yuan Tso; Chiang, Po Hui

2013-08-01

To explore the prognostic role of hydronephrosis grade in patients with pure ureteric cancer. The study included 162 patients with pure ureteric cancer who were treated between January 2005 and December 2010 at a single tertiary referral centre. The association between hydronephrosis grade with pathological findings and oncological outcomes was assessed using multivariate Cox regression analysis. Hydronephrosis grade >2 was independently associated with non-organ-confined ureteric cancer (P = 0.003). Hydronephrosis grade <2 was highly prevalent in organ-confined disease. Hydronephrosis grade >2 and bladder cancer history independently predict bladder cancer recurrence (P = 0.021 and P = 0.002, respectively) Hydronephrosis of grade >2 was found to be associated with local and distant recurrence only in univariate analysis; non-organ-confined pathology independently predicted local and distant oncological failure (P ≤ 0.001 and P = 0.002, respectively). Hydronephrosis grade >2 is associated with non-organ-confined ureteric cancer and with bladder cancer recurrence. Non-organ-confined pathology is still the most important predictor for local and distant oncological failure. © 2013 BJU International.

Atezolizumab and CYT107 in Treating Participants With Locally Advanced, Inoperable, or Metastatic Urothelial Carcinoma

ClinicalTrials.gov

2018-05-18

Metastatic Bladder Urothelial Carcinoma; Metastatic Renal Pelvis Urothelial Carcinoma; Metastatic Ureter Urothelial Carcinoma; Metastatic Urethral Urothelial Carcinoma; Metastatic Urothelial Carcinoma; Recurrent Bladder Urothelial Carcinoma; Recurrent Renal Pelvis Urothelial Carcinoma; Recurrent Ureter Urothelial Carcinoma; Recurrent Urethral Urothelial Carcinoma; Stage III Bladder Cancer AJCC v8; Stage III Renal Pelvis Cancer AJCC v8; Stage III Ureter Cancer AJCC v8; Stage III Urethral Cancer AJCC v8; Stage IV Bladder Cancer AJCC v8; Stage IV Renal Pelvis Cancer AJCC v8; Stage IV Ureter Cancer AJCC v8; Stage IV Urethral Cancer AJCC v8; Stage IVA Bladder Cancer AJCC v8; Stage IVB Bladder Cancer AJCC v8

Trends in PET Scan Usage for Imaging of Patients Diagnosed With Nonmetastatic Urologic Cancer.

PubMed

Adejoro, Oluwakayode; Alishahi, Amin; Soubra, Ayman; Konety, Badrinath

2016-02-01

The precise utility of positron emission tomography (PET) scanning for urologic cancers is not well defined. We examined the trends of usage in a population-based data set. PET scans were performed in 3.60% of patients with bladder cancer, 1.09% of those with prostate cancer, and 5.32% of those with renal cell carcinoma. This selective usage might be driven by reimbursement constraints or identification of appropriate medical indications. Positron emission tomography (PET) scanning is increasingly being used for imaging a variety of cancers, including urologic cancers. The precise utility of PET scanning for bladder cancer, prostate cancer, and renal cell carcinoma (RCC) is not yet well known. We examined the trends in PET scan usage for 3 cancers using a large population-based data set. We analyzed all individuals identified with a diagnosis of nonmetastatic bladder cancer, prostate cancer, and RCC from the Surveillance, Epidemiology, and End Results-Medicare data set for 2004 to 2009 with follow-up data available to 2010. Logistic regression analysis and χ(2) and trend tests were performed to determine the predictors of performing PET scanning. Separate models were run for each of the cancer diagnoses. All analyses were performed using SAS, version 9.3, and P < .05 was considered significant. We identified 20,865, 70,414, and 7007 patients with a diagnosis of bladder cancer, prostate cancer, and RCC, respectively, from 2004 to 2009. PET scans had been performed for 3.60% of patients with bladder cancer, 1.09% of those with prostate cancer, and 5.32% of those with RCC. On regression analysis, a more recent year of diagnosis, younger age, and high stage or grade were predictors of PET scan usage for patients with bladder cancer and RCC. A higher Gleason score and higher D'Amico risk group predicted imaging with prostate cancer. The usage of PET scanning for bladder cancer, prostate cancer, and RCC is increasing but still very selective. The selective use might be driven by a combination of reimbursement constraints and careful identification of the appropriate medical indication. Copyright © 2016 Elsevier Inc. All rights reserved.

Jarid2 is essential for the maintenance of tumor initiating cells in bladder cancer.

PubMed

Zhu, Xin-Xing; Yan, Ya-Wei; Ai, Chun-Zhi; Jiang, Shan; Xu, Shan-Shan; Niu, Min; Wang, Xiang-Zhen; Zhong, Gen-Shen; Lu, Xi-Feng; Xue, Yu; Tian, Shaoqi; Li, Guangyao; Tang, Shaojun; Jiang, Yi-Zhou

2017-04-11

Bladder cancer is the most common urologic malignancy in China, with an increase of the incidence and mortality rates over past decades. Recent studies suggest that bladder tumors are maintained by a rare fraction of cells with stem cell proprieties. Targeting these bladder tumor initiating cell (TICs) population can overcome the drug-resistance of bladder cancer. However, the molecular and genetic mechanisms regulating TICs in bladder cancer remain poorly defined. Jarid2 is implicated in signaling pathways regulating cancer cell epithelial-mesenchymal transition, and stem cell maintenance. The goal of our study was to examine whether Jarid2 plays a role in the regulation of TICs in bladder cancer. We found that knockdown of Jarid2 was able to inhibit the invasive ability and sphere-forming capacity in bladder cancer cells. Moreover, knockdown of Jarid2 reduced the proportion of TICs and impaired the tumorigenicity of bladder cancer TICs in vivo. Conversely, ectopic overexpression of Jarid2 promoted the invasive ability and sphere-forming capacity in bladder cancer cells. Mechanistically, reduced Jarid2 expression led to the upregulation of p16 and H3K27me3 level at p16 promoter region. Collectively, we provided evidence that Jarid2 via modulation of p16 is a putative novel therapeutic target for treating malignant bladder cancer.

Automobile industry occupations and bladder cancer: a population-based case-control study in southeastern Michigan, USA.

PubMed

Kobrosly, R W; Meliker, J R; Nriagu, J O

2009-10-01

To determine whether employees in the automobile industry in Michigan are at elevated risk of urinary bladder cancer. The authors conducted a population-based case-control study including 418 cases and 571 controls. History of employment within the automobile industry was coded according to the US Census Bureau Index of Occupations. Logistic regression analyses were adjusted for age at interview, cigarette smoking status, and highest education level, and used to assess associations between bladder cancer and (1) ever working in particular occupations within the automobile industry; and (2) usual occupation - defined as occupation of longest duration for each subject. Ever having worked in the automobile industry and usual employment within the industry exhibited elevated non-significant risks for bladder cancer among assembly line workers, painters and foremen. A higher risk was seen for those who worked for 20 or more years on the assembly line (OR = 2.10, 95% CI 1.15 to 3.80). Statistical interaction between usual employment on the assembly line and smoking status (>5 pack-years) was demonstrated (OR = 6.19, 95% CI 2.69 to 14.24). Among workers on the assembly line for at least 20 years, we observed an approximately twofold risk for bladder cancer. Heavy smokers working on the assembly line experience a sixfold risk for bladder cancer. Further research is necessary to verify this finding, identify the exposures that might be contributing to bladder cancer on the assembly line, and examine whether those exposures continue to persist in today's workplace.

Folate hydrolase (prostate-specific membrane [corrected] antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature.

PubMed

Samplaski, Mary K; Heston, Warren; Elson, Paul; Magi-Galluzzi, Cristina; Hansel, Donna E

2011-11-01

Folate hydrolase (prostate-specific antigen) 1 (FH(PSA)1), also known as prostate-specific membrane antigen (PSMA), is a transmembrane receptor expressed on prostate cancer cells that correlates with a more aggressive phenotype. Recent studies have demonstrated FH(PSA)1 expression in numerous benign and malignant tissue types, as well as the malignant neovasculature. As FH(PSA)1 represents a diagnostic immunomarker for prostate cancer, we explored its expression pattern in various subtypes of bladder cancer. Immunohistochemical analysis (IHC) of FH(PSA)1 was performed using tissue microarrays constructed from 167 bladder cancers, including 96 urothelial carcinomas (UCCs), 37 squamous cell carcinomas, 17 adenocarcinomas and 17 small cell carcinomas. We used a FH(PSA)1 monoclonal antibody obtained from Dako (clone 3E6, dilution 1:100), which recognizes the epitope present in the 57-134 amino acid region of the extracellular portion of the PSMA molecule. Intensity of IHC staining was scored as 0 (no expression) to 3+ (strong expression), with 2-3+ IHC considered a positive result. FH(PSA)1 demonstrated expression in a subset of bladder cancers and was most common in small cell carcinoma (3/17; 18%), with concurrent expression in non-small cell components in a subset of cases (2/6). FH(PSA)1 expression was less frequent in UCC (3/96; 3%) and adenocarcinoma (2/17; 12%). None of the squamous cell carcinomas demonstrated tumor cell expression of FH(PSA)1. However, all bladder cancers examined expressed FH(PSA)1 in the tumor vasculature, suggesting a potential role for this molecule in mediating new vessel ingrowth. FH(PSA)1 may occasionally be expressed in various subtypes of bladder cancer. These findings suggest cautious use of FH(PSA)1 as a diagnostic marker for prostatic tissue invading the bladder. The finding of FH(PSA)1 in the bladder cancer neovasculature suggests that this molecule may promote tumor growth and may represent a potential new vascular target in this disease.

MBCP - Patients - Support Groups | Center for Cancer Research

Cancer.gov

Support Groups Bladder Cancer Advocacy Network (BCAN) – a community of advocates, survivors, medical and research professionals united in support of people touched by bladder cancer. American Bladder Cancer Society (ABCS) – ABCS features a bladder cancer forum, treatment center finder, blog, and more . . .

In vivo fluorescence imaging of an orthotopic rat bladder tumor model indicates differential uptake of intravesically instilled near-infrared labeled 2-deoxyglucose analog by neoplastic urinary bladder tissues

NASA Astrophysics Data System (ADS)

Piao, Daqing; Davis, Carole A.; Hurst, Robert E.; Slaton, Joel W.

2017-02-01

Bladder cancer is one of the most expensive cancers to manage due to frequent recurrences requiring life-long surveillance and treatment. A near-infrared labeled 2-deoxy-d-glucose probe IRDye800CW-DG targeting glucose metabolism pathway has shown to enhance the sensitivity of diagnosing several types of cancers as tested on tumor models not including bladder tumor. This pilot study has explored differential uptake of intravesically administered IRDye800CW-DG in an orthotopic rat bladder tumor model. Twenty-five female Fischer rats were randomly grouped to four conditions: no-tumor-control (n=3), no-tumor-control intravesically instilled with IRDye800CWDG (n=6), rats bearing GFP-labeled AY-27 rat bladder urothelial cell carcinoma cells and washed with saline (n=5), and rats bearing AY-27 tumors and intravesically instilled with IRDye800CW-DG (n=11). Near-infrared fluorescence was measured from the opened bladder wall of anesthetized rat at an excitation wavelength of 750nm and an emission wavelength of 776nm, by using an in-house fluorescence imaging system. There is no statistically significant difference of the peak fluorescence intensity among the no-tumor-control bladders (n=3), the no-tumorcontrol bladders instilled with IRDye800CW-DG (n=6), and the GFP-labeled AY-27 treated bladders washed by saline (n=5). When compared to that of the no-tumor-control bladders instilled with IRDye800CW-DG (n=6), the fluorescence intensity of GFP-labeled AY-27 treated bladders instilled with IRDye800CW-DG and with histology confirmed neoplastic bladder tissue (n=11) was remarkably more intense (3.34 fold of over the former) and was also statistically significant (p<0.0001). The differential uptake of IRDye800CW-DG by the neoplastic urinary bladder tissues suggests the potential for cystoscopy-adaptation to enhance diagnosis and guiding surgical management of flat urinary bladder cancer.

Researchers studying alternative to bladder removal for bladder cancer patients | Center for Cancer Research

Cancer.gov

A new phase I clinical trial conducted by researchers at the Center for Cancer Research (CCR) is evaluating the safety and tolerability, or the degree to which any side effects can be tolerated by patients, of a two-drug combination as a potential alternative to bladder removal for bladder cancer patients. The trial targets patients with non-muscle invasive bladder cancer

Evaluating the effectiveness of a smoking warning label on raising patient awareness of smoking and bladder cancer.

PubMed

Johnson, B; Abouassaly, R; Ghiculete, D; Stewart, R J

2013-08-01

We assessed the knowledge of patients with regard to the association between smoking and bladder cancer, and examined the impact of a novel smoking warning label on raising awareness of this issue. We conducted a prospective cross-sectional study involving patients who presented to urology and family practice clinics. A questionnaire was used to assess knowledge regarding the association between smoking and various diseases. Participants were also asked to evaluate a novel smoking warning label for bladder cancer. A total of 291 (97%) patients responded to the questionnaire including 143 (95.3%) at urology clinics and 148 (98.7%) at family practice clinics. Overall only 45.2% of respondents were aware of the association between smoking and bladder cancer compared to 97.4% who knew that there was an association between smoking and lung cancer. There were no significant differences in knowledge between those at urology and family practice clinics. After viewing the warning label, 58.1% of respondents stated that it had changed their opinion on smoking and bladder cancer, and 74.8% felt that this label would be an effective tool to raise awareness of the issue. Patients who changed their opinion had statistically significantly less initial knowledge about the association between smoking and bladder cancer (36.7% vs 57.5% for those who did not change their opinion, p <0.001). Awareness of the link between smoking and bladder cancer remains low. The use of a smoking warning label may help raise awareness of this important public health issue. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Use of mode of action data to inform a dose-response assessment for bladder cancer following exposure to inorganic arsenic.

PubMed

Gentry, P R; Yager, J W; Clewell, R A; Clewell, H J

2014-10-01

In the recent National Research Council report on conducting a dose-response assessment for inorganic arsenic, the committee remarked that mode of action data should be used, to the extent possible, to extrapolate below the observed range for epidemiological studies to inform the shape of the dose-response curve. Recent in vitro mode of action studies focused on understanding the development of bladder cancer following exposure to inorganic arsenic provide data to inform the dose-response curve. These in vitro data, combined with results of bladder cancer epidemiology studies, inform the dose-response curve in the low-dose region, and include values for both pharmacokinetic and pharmacodynamic variability. Integration of these data provides evidence of a range of concentrations of arsenic for which no effect on the bladder would be expected. Specifically, integration of these results suggest that arsenic exposures in the range of 7-43 ppb in drinking water are exceedingly unlikely to elicit changes leading to key events in the development of cancer or noncancer effects in bladder tissue. These findings are consistent with the lack of evidence for bladder cancer following chronic ingestion of arsenic water concentrations <100 ppb in epidemiological studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Patient Burden of Bladder Outlet Obstruction after Prostate Cancer Treatment.

PubMed

Liberman, Daniel; Jarosek, Stephanie; Virnig, Beth A; Chu, Haitao; Elliott, Sean P

2016-05-01

Bladder outlet obstruction after prostate cancer therapy imposes a significant burden on health and quality of life in men. Our objective was to describe the burden of bladder outlet obstruction after prostate cancer therapy by detailing the type of procedures performed and how often those procedures were repeated in men with recurrent bladder outlet obstruction. Using SEER (Surveillance, Epidemiology and End Results)-Medicare linked data from 1992 to 2007 with followup through 2009 we identified 12,676 men who underwent at least 1 bladder outlet obstruction procedure after prostate cancer therapy, including external beam radiotherapy in 3,994, brachytherapy in 1,485, brachytherapy plus external beam radiotherapy in 1,847, radical prostatectomy in 4,736, radical prostatectomy plus external beam radiotherapy in 369 and cryotherapy in 245. Histogram, incidence rates and Cox proportional hazards models with repeat events analysis were done to describe the burden of repeat bladder outlet obstruction treatments stratified by prostate cancer therapy type. We describe the type of bladder outlet obstruction surgery grouped by level of invasiveness. At a median followup of 8.8 years 44.6% of men underwent 2 or more bladder outlet obstruction procedures. Compared to men who underwent radical prostatectomy those treated with brachytherapy and brachytherapy plus external beam radiotherapy were at increased adjusted risk for repeat bladder outlet obstruction treatment (HR 1.2 and 1.32, respectively, each p <0.05). After stricture incision the men treated with radical prostatectomy or radical prostatectomy plus external beam radiotherapy were most likely to undergo dilation at a rate of 34.7% to 35.0%. Stricture resection/ablation was more common after brachytherapy, external beam radiotherapy or brachytherapy plus external beam radiotherapy at a rate of 28.9% to 41.2%. Almost half of the men with bladder outlet obstruction after prostate cancer therapy undergo more than 1 procedure. Furthermore men with bladder outlet obstruction after radiotherapy undergo more invasive endoscopic therapies and are at higher risk for multiple treatments than men with bladder outlet obstruction after radical prostatectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Municipal distribution and trends in bladder cancer incidence in health area of León, Spain (1996-2010).

PubMed

del Canto, M; García-Martínez, L; Fernández-Villa, T; Molina, A J; Campanario, F; García-Sanz, M; López-Abente, G; Honrado, E; Martín-Sánchez, V

2015-01-01

Spain is a country where bladder cancer incidence and mortality rates are some of the highest in the world. The aim of this study is to know the incidence, trends and geographical distribution of bladder cancer in the health area of León. the new cases of bladder cancer (CIE-188) in patients residing in the health area of León and registered in the Hospital Tumor Registry of the Centro Asistencial Universitario in León (Spain) between 1996-2010 were included in this study. Triennial crude incidence and adjusted incidence rates to the worldwide and European population were calculated. Population data of the municipalities of Leon (Spain) were obtained from National Institute of Statistic of Spain (INE, Instituto Nacional de Estadística). Data were disaggregated by sex-groups and five-year age groups. Spatial distribution of smoothed municipal relative risks (RR) of bladder cancer was carried out using a Besag, York and Mollié model. Bayesian model were used to calculate the posterior probability (PP) of RR greater than one. 1.573 cases were included. Incidence rates standardized to European population increased among men from 20,8/100.000 (1996-98) to 33,1/100.000 (2006-2008) and among women these rates increased from 1,9/100.000 to 5,9/100.000 for the same period of time. No relevant differences were found in the municipal distribution of the incidences. bladder cancer incidence rates are high in the European context. Rising trends in incidence in both sexs, particularly in women are observed. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Researchers studying alternative to bladder removal for bladder cancer patients | Center for Cancer Research

Cancer.gov

A new phase I clinical trial conducted by researchers at the Center for Cancer Research (CCR) is evaluating the safety and tolerability, or the degree to which any side effects can be tolerated by patients, of a two-drug combination as a potential alternative to bladder removal for bladder cancer patients. The trial targets patients with non-muscle invasive bladder cancer (NMIBC) whose cancers have stopped responding to traditional therapies. Read more...

Molecular Dissection of Induced Platinum Resistance through Functional and Gene Expression Analysis in a Cell Culture Model of Bladder Cancer

DOE PAGES

Wang, Sisi; Zhang, Hongyong; Scharadin, Tiffany M.; ...

2016-01-22

Here, we report the development, functional and molecular characterization of an isogenic, paired bladder cancer cell culture model system for studying platinum drug resistance. The 5637 human bladder cancer cell line was cultured over ten months with stepwise increases in oxaliplatin concentration to generate a drug resistant 5637R sub cell line. The MTT assay was used to measure the cytotoxicity of several bladder cancer drugs. Liquid scintillation counting allowed quantification of cellular drug uptake and efflux of radiolabeled oxaliplatin and carboplatin. The impact of intracellular drug inactivation was assessed by chemical modulation of glutathione levels. Oxaliplatin- and carboplatin-DNA adduct formationmore » and repair was measured using accelerator mass spectrometry. Resistance factors including apoptosis, growth factor signaling and others were assessed with RNAseq of both cell lines and included confirmation of selected transcripts by RT-PCR. Oxaliplatin, carboplatin, cisplatin and gemcitabine were significantly less cytotoxic to 5637R cells compared to the 5637 cells. In contrast, doxorubicin, methotrexate and vinblastine had no cell line dependent difference in cytotoxicity. Upon exposure to therapeutically relevant doses of oxaliplatin, 5637R cells had lower drug-DNA adduct levels than 5637 cells. This difference was partially accounted for by pre-DNA damage mechanisms such as drug uptake and intracellular inactivation by glutathione, as well as faster oxaliplatin-DNA adduct repair. In contrast, both cell lines had no significant differences in carboplatin cell uptake, efflux and drug-DNA adduct formation and repair, suggesting distinct resistance mechanisms for these two closely related drugs. The functional studies were augmented by RNAseq analysis, which demonstrated a significant change in expression of 83 transcripts, including 50 known genes and 22 novel transcripts. Most of the transcripts were not previously associated with bladder cancer chemoresistance. This model system and the associated phenotypic and genotypic data has the potential to identify some novel details of resistance mechanisms of clinical importance to bladder cancer.« less

Molecular Dissection of Induced Platinum Resistance through Functional and Gene Expression Analysis in a Cell Culture Model of Bladder Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Sisi; Zhang, Hongyong; Scharadin, Tiffany M.

Here, we report the development, functional and molecular characterization of an isogenic, paired bladder cancer cell culture model system for studying platinum drug resistance. The 5637 human bladder cancer cell line was cultured over ten months with stepwise increases in oxaliplatin concentration to generate a drug resistant 5637R sub cell line. The MTT assay was used to measure the cytotoxicity of several bladder cancer drugs. Liquid scintillation counting allowed quantification of cellular drug uptake and efflux of radiolabeled oxaliplatin and carboplatin. The impact of intracellular drug inactivation was assessed by chemical modulation of glutathione levels. Oxaliplatin- and carboplatin-DNA adduct formationmore » and repair was measured using accelerator mass spectrometry. Resistance factors including apoptosis, growth factor signaling and others were assessed with RNAseq of both cell lines and included confirmation of selected transcripts by RT-PCR. Oxaliplatin, carboplatin, cisplatin and gemcitabine were significantly less cytotoxic to 5637R cells compared to the 5637 cells. In contrast, doxorubicin, methotrexate and vinblastine had no cell line dependent difference in cytotoxicity. Upon exposure to therapeutically relevant doses of oxaliplatin, 5637R cells had lower drug-DNA adduct levels than 5637 cells. This difference was partially accounted for by pre-DNA damage mechanisms such as drug uptake and intracellular inactivation by glutathione, as well as faster oxaliplatin-DNA adduct repair. In contrast, both cell lines had no significant differences in carboplatin cell uptake, efflux and drug-DNA adduct formation and repair, suggesting distinct resistance mechanisms for these two closely related drugs. The functional studies were augmented by RNAseq analysis, which demonstrated a significant change in expression of 83 transcripts, including 50 known genes and 22 novel transcripts. Most of the transcripts were not previously associated with bladder cancer chemoresistance. This model system and the associated phenotypic and genotypic data has the potential to identify some novel details of resistance mechanisms of clinical importance to bladder cancer.« less

Transforming Growth Factor-β Is an Upstream Regulator of Mammalian Target of Rapamycin Complex 2–Dependent Bladder Cancer Cell Migration and Invasion

PubMed Central

Gupta, Sounak; Hau, Andrew M.; Al-Ahmadie, Hikmat A.; Harwalkar, Jyoti; Shoskes, Aaron C.; Elson, Paul; Beach, Jordan R.; Hussey, George S.; Schiemann, William P.; Egelhoff, Thomas T.; Howe, Philip H.; Hansel, Donna E.

2017-01-01

Our prior work identified the mammalian target of rapamycin complex 2 (mTORC2) as a key regulator of bladder cancer cell migration and invasion, although upstream growth factor mediators of this pathway in bladder cancer have not been well delineated. We tested whether transforming growth factor (TGF)-β, which can function as a promotility factor in bladder cancer cells, could regulate mTORC2-dependent bladder cancer cell motility and invasion. In human bladder cancers, the highest levels of phosphorylated SMAD2, a TGF-β signaling intermediate, were present in high-grade invasive bladder cancers and associated with more frequent recurrence and decreased disease-specific survival. Increased expression of TGF-β isoforms, receptors, and signaling components was detected in invasive high-grade bladder cancer cells that expressed Vimentin and lacked E-cadherin. Application of TGF-β induced phosphorylation of the Ser473 residue of AKT, a selective target of mTORC2, in a SMAD2- and SMAD4-independent manner and increased bladder cancer cell migration in a modified scratch wound assay and invasion through Matrigel. Inhibition of TGF-β receptor I using SB431542 ablated TGF-β–induced migration and invasion. A similar effect was seen when Rictor, a key mTORC2 component, was selectively silenced. Our results suggest that TGF-β can induce bladder cancer cell invasion via mTORC2 signaling, which may be applicable in most bladder cancers. PMID:26988652

[Immunotherapy : a revolution in the management of urothelial bladder cancer ?

PubMed

Adam, Sophie Mc; Derré, Laurent; Jichlinski, Patrice; Lucca, Ilaria

2017-11-29

The treatment of urothelial bladder cancer has changed very little in recent years, with high rates of disease recurrence and progression, even in low aggressive urothelial bladder cancer. Immunotherapy has already proven its effectiveness as a treatment for several types of cancer and has been used in high-grade non-muscle-invasive bladder cancer for decades. Recent findings on immune checkpoints inhibitors have opened up a new chapter for treatment of bladder cancer, offering interesting therapeutic perspectives that could revolutionize the management.

The use of a gas chromatography-sensor system combined with advanced statistical methods, towards the diagnosis of urological malignancies

PubMed Central

Aggio, Raphael B. M.; de Lacy Costello, Ben; White, Paul; Khalid, Tanzeela; Ratcliffe, Norman M.; Persad, Raj; Probert, Chris S. J.

2016-01-01

Prostate cancer is one of the most common cancers. Serum prostate-specific antigen (PSA) is used to aid the selection of men undergoing biopsies. Its use remains controversial. We propose a GC-sensor algorithm system for classifying urine samples from patients with urological symptoms. This pilot study includes 155 men presenting to urology clinics, 58 were diagnosed with prostate cancer, 24 with bladder cancer and 73 with haematuria and or poor stream, without cancer. Principal component analysis (PCA) was applied to assess the discrimination achieved, while linear discriminant analysis (LDA) and support vector machine (SVM) were used as statistical models for sample classification. Leave-one-out cross-validation (LOOCV), repeated 10-fold cross-validation (10FoldCV), repeated double cross-validation (DoubleCV) and Monte Carlo permutations were applied to assess performance. Significant separation was found between prostate cancer and control samples, bladder cancer and controls and between bladder and prostate cancer samples. For prostate cancer diagnosis, the GC/SVM system classified samples with 95% sensitivity and 96% specificity after LOOCV. For bladder cancer diagnosis, the SVM reported 96% sensitivity and 100% specificity after LOOCV, while the DoubleCV reported 87% sensitivity and 99% specificity, with SVM showing 78% and 98% sensitivity between prostate and bladder cancer samples. Evaluation of the results of the Monte Carlo permutation of class labels obtained chance-like accuracy values around 50% suggesting the observed results for bladder cancer and prostate cancer detection are not due to over fitting. The results of the pilot study presented here indicate that the GC system is able to successfully identify patterns that allow classification of urine samples from patients with urological cancers. An accurate diagnosis based on urine samples would reduce the number of negative prostate biopsies performed, and the frequency of surveillance cystoscopy for bladder cancer patients. Larger cohort studies are planned to investigate the potential of this system. Future work may lead to non-invasive breath analyses for diagnosing urological conditions. PMID:26865331

Nanotechnology and cancer: improving real-time monitoring and staging of bladder cancer with multimodal mesoporous silica nanoparticles.

PubMed

Sweeney, Sean K; Luo, Yi; O'Donnell, Michael A; Assouline, Jose

Despite being one of the most common cancers, bladder cancer is largely inefficiently and inaccurately staged and monitored. Current imaging methods detect cancer only when it has reached "visible" size and has significantly disrupted the structure of the organ. By that time, thousands of cells will have proliferated and perhaps metastasized. Repeated biopsies and scans are necessary to determine the effect of therapy on cancer growth. In this report, we describe a novel approach based on multimodal nanoparticle contrast agent technology and its application to a preclinical animal model of bladder cancer. The innovation relies on the engineering core of mesoporous silica with specific scanning contrast properties and surface modification that include fluorescence and magnetic resonance imaging (MRI) contrast. The overall dimensions of the nano-device are preset at 80-180 nm, depending on composition with a pore size of 2 nm. To facilitate and expedite discoveries, we combined a well-known model of bladder cancer and our novel technology. We exposed nanoparticles to MB49 murine bladder cancer cells in vitro and found that 70 % of the cells were labeled by nanoparticles as measured by flow cytometry. The in vivo mouse model for bladder cancer is particularly well suited for T1- and T2-weighted MRI. Under our experimental conditions, we demonstrate that the nanoparticles considerably improve tumor definition in terms of volumetric, intensity and structural characteristics. Important bladder tumor parameters can be ascertained, non-invasively, repetitively, and with great accuracy. Furthermore, since the particles are not biodegradable, repetitive injection is not required. This feature allows follow-up diagnostic evaluations during cancer treatment. Changes in MRI signals show that in situ uptake of free particles has predilection to tumor cells relative to normal bladder epithelium. The particle distribution within the tumors was corroborated by fluorescent microscopy of sections of excised bladders. In addition, MRI imaging revealed fibrous finger-like projections into the tumors where particles insinuated themselves deeply. This morphological characteristic was confirmed by fluorescence microscopy. These findings may present new options for therapeutic intervention. Ultimately, the combination of real-time and repeated MRI evaluation of the tumors enhanced by nanoparticle contrast may have the potential for translation into human clinical studies for tumor staging, therapeutic monitoring, and drug delivery.

Bladder cancer diagnosis with CT urography: test characteristics and reasons for false-positive and false-negative results.

PubMed

Trinh, Tony W; Glazer, Daniel I; Sadow, Cheryl A; Sahni, V Anik; Geller, Nina L; Silverman, Stuart G

2018-03-01

To determine test characteristics of CT urography for detecting bladder cancer in patients with hematuria and those undergoing surveillance, and to analyze reasons for false-positive and false-negative results. A HIPAA-compliant, IRB-approved retrospective review of reports from 1623 CT urograms between 10/2010 and 12/31/2013 was performed. 710 examinations for hematuria or bladder cancer history were compared to cystoscopy performed within 6 months. Reference standard was surgical pathology or 1-year minimum clinical follow-up. False-positive and false-negative examinations were reviewed to determine reasons for errors. Ninety-five bladder cancers were detected. CT urography accuracy: was 91.5% (650/710), sensitivity 86.3% (82/95), specificity 92.4% (568/615), positive predictive value 63.6% (82/129), and negative predictive value was 97.8% (568/581). Of 43 false positives, the majority of interpretation errors were due to benign prostatic hyperplasia (n = 12), trabeculated bladder (n = 9), and treatment changes (n = 8). Other causes include blood clots, mistaken normal anatomy, infectious/inflammatory changes, or had no cystoscopic correlate. Of 13 false negatives, 11 were due to technique, one to a large urinary residual, one to artifact. There were no errors in perception. CT urography is an accurate test for diagnosing bladder cancer; however, in protocols relying predominantly on excretory phase images, overall sensitivity remains insufficient to obviate cystoscopy. Awareness of bladder cancer mimics may reduce false-positive results. Improvements in CTU technique may reduce false-negative results.

The mitochondrial C16069T polymorphism, not mitochondrial D310 (D-loop) mononucleotide sequence variations, is associated with bladder cancer.

PubMed

Shakhssalim, Nasser; Houshmand, Massoud; Kamalidehghan, Behnam; Faraji, Abolfazl; Sarhangnejad, Reza; Dadgar, Sepideh; Mobaraki, Maryam; Rosli, Rozita; Sanati, Mohammad Hossein

2013-12-05

Bladder cancer is a relatively common and potentially life-threatening neoplasm that ranks ninth in terms of worldwide cancer incidence. The aim of this study was to determine deletions and sequence variations in the mitochondrial displacement loop (D-loop) region from the blood specimens and tumoral tissues of patients with bladder cancer, compared to adjacent non-tumoral tissues. The DNA from blood, tumoral tissues and adjacent non-tumoral tissues of twenty-six patients with bladder cancer and DNA from blood of 504 healthy controls from different ethnicities were investigated to determine sequence variation in the mitochondrial D-loop region using multiplex polymerase chain reaction (PCR), DNA sequencing and southern blotting analysis. From a total of 110 variations, 48 were reported as new mutations. No deletions were detected in tumoral tissues, adjacent non-tumoral tissues and blood samples from patients. Although the polymorphisms at loci 16189, 16261 and 16311 were not significantly correlated with bladder cancer, the C16069T variation was significantly present in patient samples compared to control samples (p < 0.05). Interestingly, there was no significant difference (p > 0.05) of C variations, including C7TC6, C8TC6, C9TC6 and C10TC6, in D310 mitochondrial DNA between patients and control samples. Our study suggests that 16069 mitochondrial DNA D-Loop mutations may play a significant role in the etiology of bladder cancer and facilitate the definition of carcinogenesis-related mutations in human cancer.

The emerging role of the androgen receptor in bladder cancer.

PubMed

Lombard, Alan P; Mudryj, Maria

2015-10-01

Men are three to four times more likely to get bladder cancer than women. The gender disparity characterizing bladder cancer diagnoses has been investigated. One hypothesis is that androgen receptor (AR) signaling is involved in the etiology and progression of this disease. Although bladder cancer is not typically described as an endocrine-related malignancy, it has become increasingly clear that AR signaling plays a role in bladder tumors. This review summarizes current findings regarding the role of the AR in bladder cancer. We discuss work demonstrating AR expression in bladder cancer and its role in promoting formation and progression of tumors. Additionally, we discuss the therapeutic potential of targeting the AR in this disease. © 2015 Society for Endocrinology.

Estimating the risk of bladder and kidney cancer from exposure to low-levels of arsenic in drinking water, Nova Scotia, Canada.

PubMed

Saint-Jacques, Nathalie; Brown, Patrick; Nauta, Laura; Boxall, James; Parker, Louise; Dummer, Trevor J B

2018-01-01

Arsenic in drinking water impacts health. Highest levels of arsenic have been historically observed in Taiwan and Bangladesh but the contaminant has been affecting the health of people globally. Strong associations have been confirmed between exposure to high-levels of arsenic in drinking water and a wide range of diseases, including cancer. However, at lower levels of exposure, especially near the current World Health Organization regulatory limit (10μg/L), this association is inconsistent as the effects are mostly extrapolated from high exposure studies. This ecological study used Bayesian inference to model the relative risk of bladder and kidney cancer at these lower concentrations-0-2μg/L; 2-5μg/L and; ≥5μg/L of arsenic-in 864 bladder and 525 kidney cancers diagnosed in the study area, Nova Scotia, Canada between 1998 and 2010. The model included proxy measures of lifestyle (e.g. smoking) and accounted for spatial dependencies. Overall, bladder cancer risk was 16% (2-5μg/L) and 18% (≥5μg/L) greater than that of the referent group (<2μg/L), with posterior probabilities of 88% and 93% for these risks being above 1. Effect sizes for kidney cancer were 5% (2-5μg/L) and 14% (≥5μg/L) above that of the referent group (<2μg/L), with probabilities of 61% and 84%. High-risk areas were common in southwestern areas, where higher arsenic-levels are associated with the local geology. The study suggests an increased bladder cancer, and potentially kidney cancer, risk from exposure to drinking water arsenic-levels within the current the World Health Organization maximum acceptable concentration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Patient-centered prioritization of bladder cancer research.

PubMed

Smith, Angela B; Chisolm, Stephanie; Deal, Allison; Spangler, Alejandra; Quale, Diane Z; Bangs, Rick; Jones, J Michael; Gore, John L

2018-05-04

Patient-centered research requires the meaningful involvement of patients and caregivers throughout the research process. The objective of this study was to create a process for sustainable engagement for research prioritization within oncology. From December 2014 to 2016, a network of engaged patients for research prioritization was created in partnership with the Bladder Cancer Advocacy Network (BCAN): the BCAN Patient Survey Network (PSN). The PSN leveraged an online bladder cancer community with additional recruitment through print advertisements and social media campaigns. Prioritized research questions were developed through a modified Delphi process and were iterated through multidisciplinary working groups and a repeat survey. In year 1 of the PSN, 354 patients and caregivers responded to the research prioritization survey; the number of responses increased to 1034 in year 2. The majority of respondents had non-muscle-invasive bladder cancer (NMIBC), and the mean time since diagnosis was 5 years. Stakeholder-identified questions for noninvasive, invasive, and metastatic disease were prioritized by the PSN. Free-text questions were sorted with thematic mapping. Several questions submitted by respondents were among the prioritized research questions. A final prioritized list of research questions was disseminated to various funding agencies, and a highly ranked NMIBC research question was included as a priority area in the 2017 Patient-Centered Outcomes Research Institute announcement of pragmatic trial funding. Patient engagement is needed to identify high-priority research questions in oncology. The BCAN PSN provides a successful example of an engagement infrastructure for annual research prioritization in bladder cancer. The creation of an engagement network sets the groundwork for additional phases of engagement, including design, conduct, and dissemination. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Investigating Genetic Alterations in Bladder Cancer | Center for Cancer Research

Cancer.gov

Bladder cancer (BC) is the fifth most common cancer worldwide and the sixth most common cancer in the U.S. Mutations in a number of oncogenes and tumor suppressor genes were previously associated with invasive or noninvasive forms of the disease. More recently, next generation sequencing (NGS) of bladder tumors from over 100 Chinese patients revealed alterations in additional genes, including those encoding chromatin remodeling enzymes, like lysine specific histone demethylase 6A (KDM6A) and ARID1A, and spindle checkpoint proteins. Because the NGS studies analyzed tumors from patients of a single ethnicity, the results may not be representative of alterations in other patients. To expand on these findings, Michael Nickerson, Ph.D., and Michael Dean, Ph.D., of CCR’s Cancer and Inflammation Program and their colleagues, including Dan Theodorescu, M.D., Ph.D., Director of the University of Colorado NCI-Designated Comprehensive Cancer Center, performed exome sequencing of 14 tumors and targeted sequencing of another 40 tumors all from non-Asian patients diagnosed with BC in the U.S.

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

PubMed

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Downregulation of glutathione S-transferase M1 protein in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced mouse bladder carcinogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chuang, Jing-Jing; Dai, Yuan-Chang; Lin, Yung-Lun

2014-09-15

Bladder cancer is highly recurrent following specific transurethral resection and intravesical chemotherapy, which has prompted continuing efforts to develop novel therapeutic agents and early-stage diagnostic tools. Specific changes in protein expression can provide a diagnostic marker. In our present study, we investigated changes in protein expression during urothelial carcinogenesis. The carcinogen BBN was used to induce mouse bladder tumor formation. Mouse bladder mucosa proteins were collected and analyzed by 2D electrophoresis from 6 to 20 weeks after commencing continuous BBN treatment. By histological examination, the connective layer of the submucosa showed gradual thickening and the number of submucosal capillaries graduallymore » increased after BBN treatment. At 12-weeks after the start of BBN treatment, the urothelia became moderately dysplastic and tumors arose after 20-weeks of treatment. These induced bladder lesions included carcinoma in situ and connective tissue invasive cancer. In protein 2D analysis, the sequentially downregulated proteins from 6 to 20 weeks included GSTM1, L-lactate dehydrogenase B chain, keratin 8, keratin 18 and major urinary proteins 2 and 11/8. In contrast, the sequentially upregulated proteins identified were GSTO1, keratin 15 and myosin light polypeptide 6. Western blotting confirmed that GSTM1 and NQO-1 were decreased, while GSTO1 and Sp1 were increased, after BBN treatment. In human bladder cancer cells, 5-aza-2′-deoxycytidine increased the GSTM1 mRNA and protein expression. These data suggest that the downregulation of GSTM1 in the urothelia is a biomarker of bladder carcinogenesis and that this may be mediated by DNA CpG methylation. - Highlights: • GSTM1 and NQO-1 proteins decreased in the mouse bladder mucosa after BBN treatment. • BBN induced GSTO1 and Sp1 protein expression in the mouse bladder mucosa. • 5-Aza-2′-deoxycytidine increased GSTM1 mRNA and protein in human bladder cancer cell. • GSTM1 downregulation in the urothelia may be a biomarker of bladder carcinogenesis.« less

New clinical trial open for patients with muscle-invasive bladder cancer | Center for Cancer Research

Cancer.gov

Muscle-invasive bladder cancer is an aggressive form of bladder cancer in which the tumor invades deep into the musculature of the bladder wall, making it more likely to spread to other parts of the body. Standard treatment involves cisplatin-based chemotherapy followed by radical cystectomy, which is surgery to remove the bladder and nearby organs. However, many patients

[Recurrent urological cancer--diagnose and treatment].

PubMed

Takeshima, H; Akaza, H

1998-02-01

Clinical efforts to spare bladder function even in the case of muscle invasive recurrent bladder cancer is taking. Early detection of recurrence is essential for bladder sparing, and both urinary NMP22 and BTA are thought to have potency to detect recurrence of bladder cancer earlier than urinary cytology. Intravesical administration of BCG for superficial bladder cancer and intraarterial injection of chemoagents (Methotrexate and Cisplatin) with radiation for muscle invasive bladder cancer are thought to play important roles in sparing the bladder. Early detection of recurrent prostate cancer is becoming easier by ultrasensitive PSA assay. Though the value of early detection of recurrence is not proven since the benefits of early hormonal treatment have not yet been established, that should be a good indicator to evaluate new and coming treatments and play a important role to develop an effective treatment for recurrent prostate cancer.

Innovation in Bladder Cancer Immunotherapy.

PubMed

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.

Transforming Growth Factor-β Is an Upstream Regulator of Mammalian Target of Rapamycin Complex 2-Dependent Bladder Cancer Cell Migration and Invasion.

PubMed

Gupta, Sounak; Hau, Andrew M; Al-Ahmadie, Hikmat A; Harwalkar, Jyoti; Shoskes, Aaron C; Elson, Paul; Beach, Jordan R; Hussey, George S; Schiemann, William P; Egelhoff, Thomas T; Howe, Philip H; Hansel, Donna E

2016-05-01

Our prior work identified the mammalian target of rapamycin complex 2 (mTORC2) as a key regulator of bladder cancer cell migration and invasion, although upstream growth factor mediators of this pathway in bladder cancer have not been well delineated. We tested whether transforming growth factor (TGF)-β, which can function as a promotility factor in bladder cancer cells, could regulate mTORC2-dependent bladder cancer cell motility and invasion. In human bladder cancers, the highest levels of phosphorylated SMAD2, a TGF-β signaling intermediate, were present in high-grade invasive bladder cancers and associated with more frequent recurrence and decreased disease-specific survival. Increased expression of TGF-β isoforms, receptors, and signaling components was detected in invasive high-grade bladder cancer cells that expressed Vimentin and lacked E-cadherin. Application of TGF-β induced phosphorylation of the Ser473 residue of AKT, a selective target of mTORC2, in a SMAD2- and SMAD4-independent manner and increased bladder cancer cell migration in a modified scratch wound assay and invasion through Matrigel. Inhibition of TGF-β receptor I using SB431542 ablated TGF-β-induced migration and invasion. A similar effect was seen when Rictor, a key mTORC2 component, was selectively silenced. Our results suggest that TGF-β can induce bladder cancer cell invasion via mTORC2 signaling, which may be applicable in most bladder cancers. Copyright © 2016. Published by Elsevier Inc.

Surgical technique for en bloc transurethral resection of bladder tumour with a Hybrid Knife(®).

PubMed

Islas-García, J J O; Campos-Salcedo, J G; López-Benjume, B I; Torres-Gómez, J J; Aguilar-Colmenero, J; Martínez-Alonso, I A; Gil-Villa, S A

2016-05-01

Bladder cancer is the second most common malignancy of the urinary tract and the 9th worldwide. Latin American has an incidence of 5.6 per 100,000 inhabitants per year. Seventy-five percent of newly diagnosed cases are nonmuscle invasive bladder cancer, and 25% of cases present as muscle invasive. The mainstay of treatment for nonmuscle invasive bladder cancer is loop transurethral resection. In 2013, the group led by Dr Mundhenk of the University Hospital of Tübingen, Germany, was the first to describe the Hybrid Knife(®) equipment for performing en bloc bladder tumour resection, with favourable functional and oncological results. To describe the surgical technique of en bloc bladder tumour resection with a Hybrid Knife(®) as an alternative treatment for nonmuscle invasive bladder tumours. A male patient was diagnosed by urotomography and urethrocystoscopy with a bladder tumour measuring 2×1cm on the floor. En bloc transurethral resection of the bladder tumour was performed with a Hybrid Knife(®). Surgery was performed for 35min, with 70 watts for cutting and 50 watts for coagulation, resecting and evacuating en bloc the bladder tumour, which macroscopically included the muscle layer of the bladder. There were no complications. The technique of en bloc bladder tumour resection with Hybrid Knife(®) is an effective alternative to bipolar loop transurethral resection. Resection with a Hybrid Knife(®) is a procedure with little bleeding and good surgical vision and minimises the risk of bladder perforation and tumour implants. The procedure facilitates determining the positivity of the neoplastic process, vascular infiltration and bladder muscle invasion in the histopathology study. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Molecular biology of bladder cancer.

PubMed

Martin-Doyle, William; Kwiatkowski, David J

2015-04-01

Classic as well as more recent large-scale genomic analyses have uncovered multiple genes and pathways important for bladder cancer development. Genes involved in cell-cycle control, chromatin regulation, and receptor tyrosine and PI3 kinase-mammalian target of rapamycin signaling pathways are commonly mutated in muscle-invasive bladder cancer. Expression-based analyses have identified distinct types of bladder cancer that are similar to subsets of breast cancer, and have prognostic and therapeutic significance. These observations are leading to novel therapeutic approaches in bladder cancer, providing optimism for therapeutic progress. Copyright © 2015 Elsevier Inc. All rights reserved.

Management of bladder neck stenosis and urethral stricture and stenosis following treatment for prostate cancer.

PubMed

Nicholson, Helen L; Al-Hakeem, Yasser; Maldonado, Javier J; Tse, Vincent

2017-07-01

The aim of this review is to examine all urethral strictures and stenoses subsequent to treatment for prostate cancer, including radical prostatectomy (RP), radiotherapy, high intensity focused ultrasound (HIFU) and cryotherapy. The overall majority respond to endoscopic treatment, including dilatation, direct visual internal urethrotomy (DVIU) or bladder neck incision (BNI). There are adjunct treatments to endoscopic management, including injections of corticosteroids and mitomycin C (MMC) and urethral stents, which remain controversial and are not currently mainstay of treatment. Recalcitrant strictures are most commonly managed with urethroplasty, while recalcitrant stenosis is relatively rare yet almost always associated with bothersome urinary incontinence, requiring bladder neck reconstruction and subsequent artificial urinary sphincter (AUS) implantation, or urinary diversion for the devastated outlet.

Management of bladder neck stenosis and urethral stricture and stenosis following treatment for prostate cancer

PubMed Central

Nicholson, Helen L.; Al-Hakeem, Yasser; Maldonado, Javier J.

2017-01-01

The aim of this review is to examine all urethral strictures and stenoses subsequent to treatment for prostate cancer, including radical prostatectomy (RP), radiotherapy, high intensity focused ultrasound (HIFU) and cryotherapy. The overall majority respond to endoscopic treatment, including dilatation, direct visual internal urethrotomy (DVIU) or bladder neck incision (BNI). There are adjunct treatments to endoscopic management, including injections of corticosteroids and mitomycin C (MMC) and urethral stents, which remain controversial and are not currently mainstay of treatment. Recalcitrant strictures are most commonly managed with urethroplasty, while recalcitrant stenosis is relatively rare yet almost always associated with bothersome urinary incontinence, requiring bladder neck reconstruction and subsequent artificial urinary sphincter (AUS) implantation, or urinary diversion for the devastated outlet. PMID:28791228

Safety of three sequential whole bladder photodynamic therapy (WBPDT) treatments in the management of resistant bladder cancer

NASA Astrophysics Data System (ADS)

Mejia, Maria C.; Nseyo, Unyime O.

2009-02-01

INTRODUCTION: WBPDT has been used to treat resistant superficial bladder cancer, with clinical benefits and associated dose-dependent side effects. OBJECTIVE: The objective of this study was to assess the safety of three sequential WBPDT treatments in patients with resistant non-muscle invasive (NMI) bladder cancer. MATERIALS AND METHODS: 12 males and one female provided written informed consent in this Phase II study. Each patient received intravenous injection of Photofrin® (AXCAN Parma Inc, Canada) at 1.5 mg/kg two days prior to whole bladder laser (630nm) treatment. Assessment of safety and efficacy included weekly urinary symptoms; cystoscopy, biopsy and cytology; and measurement of bladder volume quarterly after each treatment at baseline, six and 12 months. Treatment #2 and/or #3 occurred only in the absence of bladder contracture, and/or disease progression. RESULTS: 13 patients: 12 males and one female have been enrolled and average age of enrollees is 67.1(52 - 87) years. Four patients had Ta-T1/Grade I-III tumors; two patients had CIS associated with T1/GI-III; and seven patients had carcinoma in situ (CIS) only. Three patients received 3/3 treatments, and are evaluable for toxicity; three patients received two treatments only; and seven patients received one treatment only. There was no bladder contracture; transient mild to moderate bladder irritative voiding symptoms of dysuria, urinary frequency, nocturia and urgency occurred in all patients. The three evaluable patients were without evidence of disease at average of 13.1 (7-20) months. CONCLUSION: Three sequential WBPDT treatments might have a favorable toxicity profile in the management of recurrent/ refractory non-muscle invasive bladder cancer.

Emodin modulates epigenetic modifications and suppresses bladder carcinoma cell growth.

PubMed

Cha, Tai-Lung; Chuang, Mei-Jen; Tang, Shou-Hung; Wu, Sheng-Tang; Sun, Kuang-Hui; Chen, Tzu-Ting; Sun, Guang-Huan; Chang, Sun-Yran; Yu, Cheng-Ping; Ho, Jar-Yi; Liu, Shu-Yu; Huang, Shih-Ming; Yu, Dah-Shyong

2015-03-01

The deregulation of epigenetics was involved in early and subsequent carcinogenic events. Reversing cancer epigenetics to restore a normal epigenetic condition could be a rational approach for cancer treatment and specialized prevention. In the present study, we found that the expression levels of two epigenetic markers, histone H3K27 trimethylation (H3K27me3), was low but histone H3S10 phosphorylation (pH3Ser10) was high in human bladder cancer tissues, which showed opposite expression patterns in their normal counterparts. Thus, we investigated whether a natural product, emodin, has the ability to reverse these two epigenetic modifications and inhibit bladder cancer cell growth. Emodin significantly inhibited the cell growth of four bladder cancer cell lines in a dose- and time-dependent manner. Emodin treatment did not induce specific cell cycle arrest, but it altered epigenetic modifications. Emodin treatment resulted in the suppression of pH3Ser10 and increased H3K27me3, contributing to gene silencing in bladder cancer cells. Microarray analysis demonstrated that oncogenic genes including fatty acid binding protein 4 (FABP4) and fibroblast growth factor binding protein 1 (HBP17), RGS4, tissue inhibitor of metalloproteinase 3 (TIMP3), WNT5b, URB, and collagen, type VIII, alpha 1 (COL8A1) responsible for proliferation, survival, inflammation, and carcinogenesis were significantly repressed by emodin. The ChIP assays also showed that emodin increased H3K27me3 but decreased pH3Ser10 modifications on the promoters of repressed genes, which indicate that emodin reverses the cancer epigenetics towards normal epigenetic situations. In conclusion, our work demonstrates the significant anti-neoplastic activity of emodin on bladder cancer cells and elucidates the novel mechanisms of emodin-mediated epigenetic modulation of target genes. Our study warrants further investigation of emodin as an effective therapeutic or preventive agent for bladder cancer. © 2013 Wiley Periodicals, Inc.

Long non-coding RNA ANRIL is up-regulated in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Hongxue; Department of Urology, Hospital of Xinjiang Production and Construction Corps, Urumqi 830002; Li, Xuechao

Antisense non-coding RNA in the INK4 locus (ANRIL) is a member of long non-coding RNAs and has been reported to be dysregulated in several human cancers. However, the role of ANRIL in bladder cancer remains unclear. This present study aimed to investigate whether and how ANRIL involved in bladder cancer. Our results showed up-regulation of ANRIL in bladder cancer tissues versus the corresponding adjacent non-tumor tissues. To explore the specific mechanisms, ANRIL was silenced by small interfering RNA or short hairpin RNA transfection in human bladder cancer T24 and EJ cells. Knockdown of ANRIL repressed cell proliferation and increased cellmore » apoptosis, along with decreased expression of Bcl-2 and increased expressions of Bax, cytoplasmic cytochrome c and Smac and cleaved caspase-9, caspase-3 and PARP. However, no change of cleaved caspase-8 level was observed. Furthermore, in vivo experiment confirmed that knockdown of ANRIL inhibited tumorigenic ability of EJ cells in nude mice. Meanwhile, in accordance with in vitro study, knockdown of ANRIL inhibited expression of Bcl-2 and up-regulated expressions of Bax and cleaved caspase-9, but did not affect cleaved caspase-8 level. In conclusion, we first report that ANRIL possibly serves as an oncogene in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic apoptosis pathway. - Highlights: • We first report the role of ANRIL in bladder cancer. • ANRIL is obviously up-regulated in bladder cancer tissues. • ANRIL regulates bladder cancer cell proliferation and cell apoptosis through the intrinsic pathway.« less

Future directions in bladder cancer immunotherapy: towards adaptive immunity

PubMed Central

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. PMID:26860539

Future directions in bladder cancer immunotherapy: towards adaptive immunity.

PubMed

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.

Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer.

PubMed

Weber, Lea; Schulz, Wolfgang A; Philippou, Stathis; Eckardt, Josephine; Ubrig, Burkhard; Hoffmann, Michéle J; Tannapfel, Andrea; Kalbe, Benjamin; Gisselmann, Günter; Hatt, Hanns

2018-01-01

Olfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca 2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer.

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

PubMed

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.

Occupational risk factors for male bladder cancer: results from a population based case cohort study in the Netherlands.

PubMed

Zeegers, M P; Swaen, G M; Kant, I; Goldbohm, R A; van den Brandt, P A

2001-09-01

This study was conducted to estimate risk of bladder cancer associated with occupational exposures to paint components, polycyclic aromatic hydrocarbons (PAHs), diesel exhausts, and aromatic amines among the general population in The Netherlands. A prospective cohort study was conducted among 58,279 men. In September 1986, the cohort members (55-69 years) completed a self administered questionnaire on risk factors for cancer including job history. Follow up for incident bladder cancer was established by linkage to cancer registries until December 1992. A case-cohort approach was used based on 532 cases and 1630 subcohort members. A case by case expert assessment was carried out to assign to the cases and subcohort members a cumulative probability of occupational exposure for each carcinogenic exposure. Men in the highest tertiles of occupational exposure to paint components, PAHs, aromatic amines, and diesel exhaust had non-significantly higher age and smoking adjusted incident rate ratios (RRs) of bladder cancer than men with no exposure: 1.29 (95% confidence interval (95% CI) 0.71 to 2.33), 1.24 (95% CI 0.68 to 2.27), 1.32 (95% CI 0.41 to 4.23) and 1.21 (95% CI 0.78 to 1.88), respectively. The associations between paint components and PAHs and risk of bladder cancer were most pronounced for current smokers. Among former smokers it seemed that for cumulative probability of exposure to paint components and PAHs, men who had smoked more than 15 cigarettes a day had RRs below unity compared with men who had smoked less than 15 cigarettes a day, whereas among current smokers the opposite was found. Exposure to diesel exhaust was positively associated with risk of bladder cancer among current and former smokers who had smoked more than 15 cigarettes a day. This study provided only marginal evidence for an association between occupational exposure to paint components, PAHs, aromatic amines, and bladder cancer. Despite the small proportion of exposed subjects, an interaction with cigarette smoking was found, specifically for paint components, suggesting that the carcinogenic effect on the bladder might decrease after stopping smoking.

Accuracy of contrast-enhanced ultrasound in the detection of bladder cancer

PubMed Central

Nicolau, C; Bunesch, L; Peri, L; Salvador, R; Corral, J M; Mallofre, C; Sebastia, C

2011-01-01

Objective To assess the accuracy contrast-enhanced ultrasound (CEUS) in bladder cancer detection using transurethral biopsy in conventional cystoscopy as the reference standard and to determine whether CEUS improves the bladder cancer detection rate of baseline ultrasound. Methods 43 patients with suspected bladder cancer underwent conventional cystoscopy with transurethral biopsy of the suspicious lesions. 64 bladder cancers were confirmed in 33 out of 43 patients. Baseline ultrasound and CEUS were performed the day before surgery and the accuracy of both techniques for bladder cancer detection and number of detected tumours were analysed and compared with the final diagnosis. Results CEUS was significantly more accurate than ultrasound in determining presence or absence of bladder cancer: 88.37% vs 72.09%. Seven of eight uncertain baseline ultrasound results were correctly diagnosed using CEUS. CEUS sensitivity was also better than that of baseline ultrasound per number of tumours: 65.62% vs 60.93%. CEUS sensitivity for bladder cancer detection was very high for tumours larger than 5 mm (94.7%) but very low for tumours <5 mm (20%) and also had a very low negative predictive value (28.57%) in tumours <5 mm. Conclusion CEUS provided higher accuracy than baseline ultrasound for bladder cancer detection, being especially useful in non-conclusive baseline ultrasound studies. PMID:21123306

Endoscopic Optical Coherence Tomography in Urology

NASA Astrophysics Data System (ADS)

Pan, Yingtian; Waltzer, Wayne; Ye, Zhangqun

Clinical statistics has shown a stable prevalence of bladder cancer in recent years, which by far remains among the most common types of malignancy in the USA. With smoking as the most well-established risk factor, bladder cancer is the fourth most common cancer occurrences in male population [1]. In the year of 2014, an estimated 74,690 new cases are expected to occur with estimated 15,580 deaths. Bladder cancer often refers to transitional cell carcinoma (TCC) as it originates primarily from the epithelial cell layer (i.e., urothelium) of the bladder. Unlike prostate-specific antigen (PSA) for prostate cancer screening, there is currently no effective screening technique approved or recommended for the population at average risk [2-5]. As a result, hematuria (i.e., blood in the urine) is often the first clinical symptom of bladder cancer. Fortunately, urinary bladder is more accessible than prostate glands endoscopically; thus cytology following white-light cystoscopy has been the gold standard for current clinical detection of bladder cancer. This is important because bladder cancer if diagnosed prior to muscle invasion (e.g., superficial or at

Sorafenib induces cathepsin B-mediated apoptosis of bladder cancer cells by regulating the Akt/PTEN pathway. The Akt inhibitor, perifosine, enhances the sorafenib-induced cytotoxicity against bladder cancer cells

PubMed Central

Amantini, Consuelo; Morelli, Maria Beatrice; Santoni, Matteo; Soriani, Alessandra; Cardinali, Claudio; Farfariello, Valerio; Eleuteri, Anna Maria; Bonfili, Laura; Mozzicafreddo, Matteo; Nabissi, Massimo; Cascinu, Stefano; Santoni, Giorgio

2015-01-01

Sorafenib, a tyrosine kinase inhibitor, has been demonstrated to exert anti-tumor effects. However, the molecular mechanisms underlying its effects on bladder cancer remain unknown. Here, we evaluated the mechanisms responsible for the sorafenib-induced anti-tumor effects on 5637 and T24 bladder cancer cells. We demonstrated that sorafenib reduces cell viability, stimulates lysosome permeabilization and induces apoptosis of bladder cancer cells. These effects are dependent by the activation of cathepsin B released from lysosomes. The sorafenib-increased cathepsin B activity induced the proteolysis of Bid into tBid that stimulates the intrinsic pathway of apoptosis characterized by mitochondrial membrane depolarization, oxygen radical generation and cytochrome c release. Moreover, we found that cathepsin B enzymatic activity, induced by sorafenib, is dependent on its dephosphorylation via PTEN activation and Akt inactivation. Pretreatment with orthovanadate rescued bladder cancer cells from apoptosis. In addition, the Akt inhibitor perifosine increased the sensitivity of bladder cancer cells to sorafenib-induced cytotoxicity. Overall, our results show that apoptotic cell death induced by sorafenib in bladder cancer cells is dependent on cathepsin B activity and involved PTEN and Akt signaling pathways. The Akt inhibitor perifosine increased the cytotoxic effects of sorafenib in bladder cancer cells. PMID:26097873

Air pollution and risk of urinary bladder cancer in a case-control study in Spain.

PubMed

Castaño-Vinyals, Gemma; Cantor, Kenneth P; Malats, Núria; Tardon, Adonina; Garcia-Closas, Reina; Serra, Consol; Carrato, Alfredo; Rothman, Nathaniel; Vermeulen, Roel; Silverman, Debra; Dosemeci, Mustafa; Kogevinas, Manolis

2008-01-01

Air pollution has been associated with an increased risk for lung cancer. We examined whether long-term air pollution is associated with bladder cancer risk. Information from a case-control study in Spain that included 1219 incident cases and 1271 hospital controls was used. Information on residential history including several indicators of exposure to air pollution and other potential risk factors was collected in a face-to-face computerised personal interview. Odds ratios (OR) and 95% confidence intervals (95% CI) were adjusted for age, gender, region, smoking, occupation, water contaminants and diet. Living more than 40 years in a city with a population of more than 100 000 was associated with an increased risk for bladder cancer overall (OR 1.30, 95% CI 1.04 to 1.63). Emissions of polycyclic aromatic hydrocarbons and diesel from industries near the residence, as evaluated by experts, were associated with an increased risk (OR 1.29, 95% CI 0.85 to 1.98), while lower or no excess risks were observed for other pollution-related variables. Odds ratios among never smokers tended to be higher than among smokers. The small to moderate positive associations found for several indices of air pollution and bladder cancer, while suggestive of excess risk, require further evaluation in other settings.

Meat and components of meat and the risk of bladder cancer in the NIH-AARP Diet and Health Study.

PubMed

Ferrucci, Leah M; Sinha, Rashmi; Ward, Mary H; Graubard, Barry I; Hollenbeck, Albert R; Kilfoy, Briseis A; Schatzkin, Arthur; Michaud, Dominique S; Cross, Amanda J

2010-09-15

Meat could be involved in bladder carcinogenesis via multiple potentially carcinogenic meat-related compounds related to cooking and processing, including nitrate, nitrite, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs). The authors comprehensively investigated the association between meat and meat components and bladder cancer. During 7 years of follow-up, 854 transitional cell bladder-cancer cases were identified among 300,933 men and women who had completed a validated food-frequency questionnaire in the large prospective NIH-AARP Diet and Health Study. The authors estimated intake of nitrate and nitrite from processed meat and HCAs and PAHs from cooked meat by using quantitative databases of measured values. Total dietary nitrate and nitrite were calculated based on literature values. The hazard ratios (HR) and 95% confidence intervals (CI) for red meat (HR for fifth quintile compared with first quintile, 1.22; 95% CI, 0.96-1.54; P(trend) = .07) and the HCA 2-amino-1 methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) (HR, 1.19; 95% CI, 0.95-1.48; P(trend) = .06) conferred a borderline statistically significant increased risk of bladder cancer. Positive associations were observed in the top quintile for total dietary nitrite (HR, 1.28; 95% CI, 1.02-1.61; P(trend) = .06) and nitrate plus nitrite intake from processed meat (HR, 1.29; 95% CI, 1.00-1.67; P(trend) = .11). These findings provided modest support for an increased risk of bladder cancer with total dietary nitrite and nitrate plus nitrite from processed meat. Results also suggested a positive association between red meat and PhIP and bladder carcinogenesis. © 2010 American Cancer Society.

The Associations of Psychological Stress with Depressive and Anxiety Symptoms among Chinese Bladder and Renal Cancer Patients: The Mediating Role of Resilience

PubMed Central

Li, Mengyao; Wang, Lie

2016-01-01

Background The prevalence of depressive and anxiety symptoms and their associated factors in bladder and renal cancer patients are not well evaluated in China. Given the growing attention to positive psychological constructs in the field of oncology, it is necessary to explore the effects of these constructs on depressive and anxiety symptoms. This study aims to explore the associations of psychological stress with depressive and anxiety symptoms among Chinese bladder and renal cancer patients and the mediating role of resilience in these relationships. Methods A cross-sectional study was conducted at the First Affiliated Hospital of China Medical University in Liaoning province. 327 bladder cancer patients and 268 renal cancer patients completed questionnaires on demographic variables, the Center for Epidemiologic Studies Depression Scale, Zung Self-Rating Anxiety Scale, Resilience Scale-14, and Perceived Stress Scale-10 during the period from July 2013 to July 2014. Hierarchical linear regression analyses were performed to explore the mediating role of resilience. Results The prevalence of depressive and anxiety symptoms was 78.0% and 71.3% in bladder cancer patients, and 77.6% and 68.3% in renal cancer patients. Psychological stress was positively related to depressive and anxiety symptoms, while resilience was negatively related to these symptoms. Resilience partially mediated the relations of psychological stress with depressive and anxiety symptoms. Conclusions The high prevalence of depressive and anxiety symptoms among Chinese bladder and renal cancer patients should receive more attention from medical institutions and government agencies. In addition to reducing depressive and anxiety symptoms, resilience development should be included in depression and anxiety prevention and treatment strategies in China. PMID:27128438

Utility of Recent Studies to Assess the National Research Council 2001 Estimates of Cancer Risk from Ingested Arsenic

PubMed Central

Gibb, Herman; Haver, Cary; Gaylor, David; Ramasamy, Santhini; Lee, Janice S.; Lobdell, Danelle; Wade, Timothy; Chen, Chao; White, Paul; Sams, Reeder

2011-01-01

Objective The purpose of this review is to evaluate the impact of recent epidemiologic literature on the National Research Council (NRC) assessment of the lung and bladder cancer risks from ingesting low concentrations (< 100 μg/L) of arsenic-contaminated water. Data sources, extraction, and synthesis PubMed was searched for epidemiologic studies pertinent to the lung and bladder cancer risk estimates from low-dose arsenic exposure. Articles published from 2001, the date of the NRC assessment, through September 2010 were included. Fourteen epidemiologic studies on lung and bladder cancer risk were identified as potentially useful for the analysis. Conclusions Recent epidemiologic studies that have investigated the risk of lung and bladder cancer from low arsenic exposure are limited in their ability to detect the NRC estimates of excess risk because of sample size and less than lifetime exposure. Although the ecologic nature of the Taiwanese studies on which the NRC estimates are based present certain limitations, the data from these studies have particular strengths in that they describe lung and bladder cancer risks resulting from lifetime exposure in a large population and remain the best data on which to conduct quantitative risk assessment. Continued follow-up of a population in northeastern Taiwan, however, offers the best opportunity to improve the cancer risk assessment for arsenic in drinking water. Future studies of arsenic < 100 μg/L in drinking water and lung and bladder cancer should consider adequacy of the sample size, the synergistic relationship of arsenic and smoking, duration of arsenic exposure, age when exposure began and ended, and histologic subtype. PMID:21030336

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoue, Masaharu; Koga, Fumitaka, E-mail: f-koga@cick.jp; Yoshida, Soichiro

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 TURBTmore » 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-sparing protocol. ERBB 2-targeting treatment may improve the outcomes of such patients.« less

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.

PubMed

Inoue, Masaharu; Koga, Fumitaka; Yoshida, Soichiro; Tamura, Tomoki; Fujii, Yasuhisa; Ito, Eisaku; Kihara, Kazunori

2014-10-01

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. 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. 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). ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder-sparing protocol. ERBB 2-targeting treatment may improve the outcomes of such patients. Copyright © 2014 Elsevier Inc. All rights reserved.

The Impact of Multiple Malignancies on Patients with Bladder Carcinoma: A Population-Based Study Using the SEER Database

PubMed Central

Ehrlich, Joshua R.; Schwartz, Michael J.; Ng, Casey K.; Kauffman, Eric C.; Scherr, Douglas S.

2009-01-01

Purpose. To date, no study has examined a population-based registry to determine the impact of multiple malignancies on survival of bladder cancer patients. Our experience suggests that bladder cancer patients with multiple malignancies may have relatively positive outcomes. Materials & Methods. We utilized data from the Surveillance Epidemiology and End Results (SEERs) database to examine survival between patients with only bladder cancer (BO) and with bladder cancer and additional cancer(s) antecedent (AB), subsequent (BS), or antecedent and subsequent to bladder cancer (ABS). Results. Analyses demonstrated diminished survival among AB and ABS cohorts. However, when cohorts were substratified by stage, patients in the high-stage BS cohort appeared to have a survival advantage over high-stage BO patients. Conclusions. Bladder cancer patients with multiple malignancies have diminished survival. The survival advantage of high-stage BS patients is likely a statistical phenomenon. Such findings are important to shape future research and to improve our understanding of patients with multiple malignancies. PMID:20069054

Inhibition of NEDD4 inhibits cell growth and invasion and induces cell apoptosis in bladder cancer cells.

PubMed

Wen, Wu; Li, Jingying; Wang, Longwang; Xing, Yifei; Li, Xuechao; Ruan, Hailong; Xi, Xiaoqing; Xiong, Jianhua; Kuang, Renrui

2017-08-18

The neural precursor cell expressed developmentally downregulated protein 4 (NEDD4) plays a pivotal oncogenic role in various types of human cancers. However, the function of NEDD4 in bladder cancer has not been fully investigated. In the present study, we aim to explore whether NEDD4 governs cell proliferation, apoptosis, migration, and invasion in bladder cancer cells. Our results showed that downregulation of NEDD4 suppressed cell proliferation in bladder cancer cells. Moreover, we found that inhibition of NEDD4 significantly induced cell apoptosis. Furthermore, downregulation of NEDD4 retarded cell migration and invasion. Notably, overexpression of NEDD4 enhanced cell growth and inhibited apoptosis. Consistently, upregulation of NEDD4 promoted cell migration and invasion in bladder cancer cells. Mechanically, our Western blotting results revealed that downregulation of NEDD4 activated PTEN and inhibited Notch-1 expression, whereas upregulation of NEDD4 reduced PTEN level and increased Notch-1 level in bladder cancer cells. Our findings indicated that NEDD4 exerts its oncogenic function partly due to regulation of PTEN and Notch-1 in bladder cancer cells. These results further revealed that targeting NEDD4 could be a useful approach for the treatment of bladder cancer.

MicroRNA-490-5p inhibits proliferation of bladder cancer by targeting c-Fos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Shiqi; Xu, Xianglai; Xu, Xin

2013-11-29

Highlights: •We examined the level of miR-490-5p in bladder cancer tissues and three cancer cell lines. •We are the first to show the function of miR-490-5p in bladder cancer. •We demonstrate c-Fos may be a target of miR-490-5p. -- Abstract: MicroRNAs (miRNAs) are non-protein-coding sequences that play a crucial role in tumorigenesis by negatively regulating gene expression. Here, we found that miR-490-5p is down-regulated in human bladder cancer tissue and cell lines compared to normal adjacent tissue and a non-malignant cell line. To better characterize the function of miR-490-5p in bladder cancer, we over-expressed miR-490-5p in bladder cancer cell linesmore » with chemically synthesized mimics. Enforced expression of miR-490-5p in bladder cancer cells significantly inhibited the cell proliferation via G1-phase arrest. Further studies found the decreased c-Fos expression at both mRNA and protein levels and Luciferase reporter assays demonstrated that c-Fos is a direct target of miR-490-5p in bladder cancer. These findings indicate miR-490-5p to be a novel tumor suppressor of bladder cancer cell proliferation through targeting c-Fos.« less

Clinical and pathological implications of miRNA in bladder cancer.

PubMed

Braicu, Cornelia; Cojocneanu-Petric, Roxana; Chira, Sergiu; Truta, Anamaria; Floares, Alexandru; Petrut, Bogdan; Achimas-Cadariu, Patriciu; Berindan-Neagoe, Ioana

2015-01-01

MicroRNAs (miRNAs) are small, noncoding RNA species with a length of 20-22 nucleotides that are recognized as essential regulators of relevant molecular mechanisms, including carcinogenesis. Current investigations show that miRNAs are detectable not only in different tissue types but also in a wide range of biological fluids, either free or trapped in circulating microvesicles. miRNAs were proven to be involved in cell communication, both in pathological and physiological processes. Evaluation of the global expression patterns of miRNAs provides key opportunities with 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.

Epidemiologic survey of bladder cancer in greater New Orleans.

PubMed

Sullivan, J W

1982-08-01

Primary ancestry of the patients and controls in this study was not statistically different but the Jewish population had a significantly increased incidence of bladder cancer. Over-all, a significantly greater number of patients smoked filtered cigarettes, began drinking artificially sweetened beverages at an earlier age, drank artificially sweetened beverages for a greater number of years, consumed a greater number of glasses of artificially sweetened beverages weekly and related a history of urinary tract infections. A significantly increased incidence of bladder cancer was noted in individuals employed by certain types of companies, by certain job titles and by certain job material handled. Analysis of the data failed to show any significant difference in years of consumption of coffee, amount of various types of coffee or tea consumed, consumption of various nonalcoholic and alcoholic beverages, including source of drinking water, use of hair dye, incidence of diabetes mellitus, family history of urinary cancer and a history of pelvic irradiation or bladder stones.

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

PubMed

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.

The epidemiological and histological trend of bladder cancer in Iran.

PubMed

Rafiemanesh, Hosein; Lotfi, Zahra; Bakhtazad, Sima; Ghoncheh, Mahshid; Salehiniya, Hamid

2018-01-01

Bladder cancer is the ninth common cancer in the world, the third common cancer among men in the Arabic and Western Asian countries, and the second in some regions of Iran (a country in the Middle East). There was no study on the epidemiological and histological trend of bladder cancer in Iran. This study aimed to the epidemiological and histological trend of bladder cancer in Iran. In this study, data were extracted from annual cancer registry reports of Iranian Ministry of Health between 2003 and 2008. Standardized incidence rates were calculated using the world standard population and incidence rate was calculated by age groups, sex, and histological type. Data on epidemiologic trend and histology were analyzed using Joinpoint software package. A total of 23,291 cases were reported. Almost 17.70% (4127 cases) were women and 82.30% (19,170 cases) men. The sex ratio (male to female) was 4.65. Joinpoint analysis showed the significant increased trend of age-standardized incidence rate (ASIR) for both sexes. The annual percentage change of standardized incidence rate was 11.5 (confidence interval [CI]: 9.0-14.0) in women and 10.8 (CI: 8.0-13.6) in men. Two histological types of transitional cell carcinoma (TCC), not otherwise specified and papillary TCC included 43.89% and 49.86% of all cancer cases, respectively. According to this study the trend of ASIR of bladder cancer in Iran is rising, so it is necessary to conduct further researches in future to provide accurate information on the cancer and investigate related risk factors and implement prevention programs in Iran.

Decision curve analysis assessing the clinical benefit of NMP22 in the detection of bladder cancer: secondary analysis of a prospective trial.

PubMed

Barbieri, Christopher E; Cha, Eugene K; Chromecki, Thomas F; Dunning, Allison; Lotan, Yair; Svatek, Robert S; Scherr, Douglas S; Karakiewicz, Pierre I; Sun, Maxine; Mazumdar, Madhu; Shariat, Shahrokh F

2012-03-01

• To employ decision curve analysis to determine the impact of nuclear matrix protein 22 (NMP22) on clinical decision making in the detection of bladder cancer using data from a prospective trial. • The study included 1303 patients at risk for bladder cancer who underwent cystoscopy, urine cytology and measurement of urinary NMP22 levels. • We constructed several prediction models to estimate risk of bladder cancer. The base model was generated using patient characteristics (age, gender, race, smoking and haematuria); cytology and NMP22 were added to the base model to determine effects on predictive accuracy. • Clinical net benefit was calculated by summing the benefits and subtracting the harms and weighting these by the threshold probability at which a patient or clinician would opt for cystoscopy. • In all, 72 patients were found to have bladder cancer (5.5%). In univariate analyses, NMP22 was the strongest predictor of bladder cancer presence (predictive accuracy 71.3%), followed by age (67.5%) and cytology (64.3%). • In multivariable prediction models, NMP22 improved the predictive accuracy of the base model by 8.2% (area under the curve 70.2-78.4%) and of the base model plus cytology by 4.2% (area under the curve 75.9-80.1%). • Decision curve analysis revealed that adding NMP22 to other models increased clinical benefit, particularly at higher threshold probabilities. • NMP22 is a strong, independent predictor of bladder cancer. • Addition of NMP22 improves the accuracy of standard predictors by a statistically and clinically significant margin. • Decision curve analysis suggests that integration of NMP22 into clinical decision making helps avoid unnecessary cystoscopies, with minimal increased risk of missing a cancer. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

The relationship between promoter methylation of p16 gene and bladder cancer risk: a meta-analysis

PubMed Central

Qi, Defeng; Li, Jinhui; Jiang, Mei; Liu, Chenli; Hu, Yuan; Li, Mengxi; Su, Jialin; Que, Biao; Ji, Weidong

2015-01-01

Purpose: Many scientific evidences suggested that the methylation of p16INK4a (p16) was associated with bladder cancer, but some existing studies have yielded inconclusive results about the relationship between p16 promoter methylation and pathological features or the tumor grade of bladder cancer. This meta-analysis of studies aims to evaluate the clinical and prognostic significance of p16 methylation in bladder carcinogenesis. Methods: Studies were systemically searched via PubMed and Google Scholar in English up to Sept 2015 and a total of ten appropriate studies (693 cases and 290 controls) with an average NOS score of 6.8 were included. The quality of the appropriate studies was measured by the Newcastle-Ottawa Scale (NOS) assessment. Results: The meta-analysis results revealed that the methylation state of p16 was statistically significantly associated with an increased risk of bladder cancer (OR=6.71, 95% CI=3.79-11.87) compared to control, and there is no statistically significantly association between the p16 methylation and the tumor pTNM staging (OR=0.59, 95% CI=0.22-1.60) or the tumor grade (OR=1.01, 95% CI=0.52-1.94) in p16 methylated patients compared to unmethylated patients. Conclusions: our meta-analysis indicates that p16 promoter methylation may be a promising biomarker for the diagnosis of bladder cancer and the inactivation of p16 may be an early event in bladder carcinogenesis. More studies with larger numbers of participants worldwide are needed to further identify the obvious association above. PMID:26884993

Implication of androgen receptor in urinary bladder cancer: a critical mini review.

PubMed

Rahmani, Arshad H; Alzohairy, Mohammad; Babiker, Ali Yousif Y; Khan, Amjad A; Aly, Salah M; Rizvi, Moshahid A

2013-01-01

Cancer is probably the most dreaded disease of mankind and the bladder cancer is the fifth most common type of cancer worldwide. It is a major cause of cancer morbidity and mortality. From amongst the bladder cancer, the Transitional Cell Carcinoma (TCC) is the most prevalent cancer of the bladder and accounts for 90% of all bladder cancer cases. Despite such a high prevalence, the molecular mechanism involved in the induction of bladder carcinoma and its progression are poorly understood. Tumorigenesis and tumor progression of bladder carcinomas are thought to result from the accumulation of multiple genetic alterations. The Androgen Receptor (AR) gene is located on the q arm of X chromosome (q11-12) and considered as a ligand-inducible transcription factor that regulates target gene expression. The Androgen plays a vital role in the development and maintenance of the normal urinary bladder. The AR is also involved in the development and progression of urinary bladder carcinoma, which is the most common type of carcinoma. Mutation in AR alters the ligand binding ability that may cause the progression and development of bladder cancer. Tumorigenesis and tumor progression are thought to result from changes in the function of hormonal receptor gene. The accumulation of the changes in AR expressions, determines the tumor's phenotype and ultimately the patient's clinical outcome. The early detection of which may help in management and prediction, how will it behave and respond to the therapeutic regimen. The present review aimed to study the mechanism and alteration of AR gene that play a vital role in the tumorIgenesis of bladder carcinoma.

Clinical characteristics of bladder cancer in patients with spinal cord injury: the experience from a single centre.

PubMed

Böthig, Ralf; Kurze, Ines; Fiebag, Kai; Kaufmann, Albert; Schöps, Wolfgang; Kadhum, Thura; Zellner, Michael; Golka, Klaus

2017-06-01

Life expectancy for people with spinal cord injury has shown a marked increase due to modern advances in treatment methods and in neuro-urology. However, since life expectancy of people with paralysis increases, the risk of developing of urinary bladder cancer is gaining importance. Single-centre retrospective evaluation of patient data with spinal cord injuries and proven urinary bladder cancer and summary of the literature. Between 1998 and 2014, 24 (3 female, 21 male) out of a total of 6599 patients with spinal cord injury were diagnosed with bladder cancer. The average age at bladder cancer diagnosis was 57.67 years, which is well below the average for bladder cancer cases in the general population (male: 73, female: 77). All but one patient had a latency period between the onset of the spinal paralysis and tumour diagnosis of more than 10 years. The median latency was 29.83 years. The median survival for these patients was 11.5 months. Of the 24 patients, 19 (79%) had muscle invasive bladder cancer at ≥T2 at the time of diagnosis. The type of neurogenic bladder (neurogenic detrusor overactivity or acontractility) and the form of bladder drainage do not appear to influence the risk. Long-term indwelling catheter drainage played only a minor role in the investigated patients. The significantly younger age at onset and the frequency of invasive tumours at diagnosis indicate that spinal cord injury influences bladder cancer risk and prognosis as well. Early detection of bladder cancer in patients with spinal cord injury remains a challenge.

Bladder cancer.

PubMed

Patton, Suzanne E; Hall, M Craig; Ozen, Haluk

2002-05-01

Bladder cancer is a common and chemotherapy-responsive tumor, related to tobacco smoking, environmental arsenic exposure, industrial dye exposure, and parasitic schistosomiasis exposure. Both reduction of carcinogen exposure and chemoprevention, possibly with cyclooxygenase 2 inhibitors, should reduce the incidence. The search for the ideal screening and monitoring test continues with some promising new candidates, including survivin. Although 10-year survival can be achieved in 87% of early-stage patients with muscle-invasive disease rendered T(0) and 57% of those rendered T(1) at second look after transurethral resection bladder tumor, most still require radical cystectomy. Continued improvements in surgical techniques permit gains in quality of life after the procedure. Ten-year survival can still be achieved with cystectomy in the face of grossly positive lymph nodes in 32% of T(2) and 10% of T(3) patients. A recent meta-analysis indicates that preoperative irradiation is unlikely to be beneficial, but definitive chemoradiation can produce significant 5-year survival rates in nonoperative candidates and those desiring bladder preservation. The Intergroup now has preliminary data from a Southwest Oncology Group-based trial showing a significant benefit for neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin. The regimen of gemcitabine and cisplatin is equally efficacious with less toxicity than methotrexate, vinblastine, doxorubicin, and cisplatin. It has been adopted as the standard arm in a phase III trial for advanced bladder cancer, comparing it with the triplet of gemcitabine, paclitaxel, and cisplatin. Other active agents in bladder cancer include ifosfamide, carboplatin, docetaxel, and vinorelbine, and various doublets of these agents are being tested in phase II trials, with promising results.

FGF2-mediated reciprocal tumor cell-endothelial cell interplay contributes to the growth of chemoresistant cells: a potential mechanism for superficial bladder cancer recurrence.

PubMed

Chen, Yule; Zhu, Guodong; Wu, Kaijie; Gao, Yang; Zeng, Jin; Shi, Qi; Guo, Peng; Wang, Xinyang; Chang, Luke S; Li, Lei; He, Dalin

2016-04-01

Patients with superficial bladder cancer can be definitively cured by one single transurethral resection (TUR) with additional intravesical chemotherapy; however, up to 75 % of cases display frequent and multiple recurrences. One of the major causes of recurrence is that chemotherapeutic drugs used in intravesical regimens may induce chemoresistance. However, the mechanisms by which these chemoresistant cells develop into recurrent tumors remain unclear. Recent clinical evidence revealed that the expression of pro-angiogenic factor FGF2 was associated with early local relapse in patients with superficial bladder cancer. In this study, we conducted a preliminary investigation of the mechanisms of chemoresistant cells mediated bladder cancer recurrence, focusing on FGF2-initiated tumor cell-endothelial cell interaction on chemoresistant cancer cell growth. We found that the expression of FGF2 was increased in chemoresistant bladder cell lines and in bladder tissues after intravesical chemotherapy. Although chemoresistant bladder cells grow slower than parental cells, chemoresistant bladder cancer cells had stronger ability than parental cells to stimulate endothelial cell migration, growth, and tube formation by producing FGF2. Inversely, endothelial cells significantly promoted chemoresistant bladder cancer growth in vitro and in vivo. Thus, targeting chemotherapy-induced FGF2 upregulation may provide a promising approach to manage the recurrence of superficial bladder cancer.

Genome-wide screening and identification of long noncoding RNAs and their interaction with protein coding RNAs in bladder urothelial cell carcinoma.

PubMed

Wang, Longxin; Fu, Dian; Qiu, Yongbin; Xing, Xiaoxiao; Xu, Feng; Han, Conghui; Xu, Xiaofeng; Wei, Zhifeng; Zhang, Zhengyu; Ge, Jingping; Cheng, Wen; Xie, Hai-Long

2014-07-10

To understand lncRNAs expression profiling and their potential functions in bladder cancer, we investigated the lncRNA and coding RNA expression on human bladder cancer and normal bladder tissues. Bioinformatic analysis revealed thousands of significantly differentially expressed lncRNAs and coding mRNA in bladder cancer relative to normal bladder tissue. Co-expression analysis revealed that 50% of lncRNAs and coding RNAs expressed in the same direction. A subset of lncRNAs might be involved in mTOR signaling, p53 signaling, cancer pathways. Our study provides a large scale of co-expression between lncRNA and coding RNAs in bladder cancer cells and lays biological basis for further investigation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

[Can MRI be used to distinguish between superficial and invasive transitional cell bladder cancer?].

PubMed

Tillou, X; Grardel, E; Fourmarier, M; Bernasconi, T; Demailly, M; Hakami, F; Saint, F; Petit, J

2008-07-01

To determine the sensitivity and specificity of MRI to distinguish between superficial and invasive transitional cell bladder cancer. Sixty patients (52 men and eight women) with a mean age of 66.8 years were assessed by bladder MRI between May 2002 and November 2005 for a primary bladder cancer diagnosed by endoscopy, followed by transurethral resection and histological examination of the bladder cancer. Patients presenting a discordance between MRI findings and histological examination were analysed. Imaging and pathology staging was concordant for 49 bladder cancers (40 superficial and nine invasive). Ten tumours considered to be invasive on MRI were superficial on histological examination and six of them relapsed at the resection scar at one or three months. The sensitivity of MRI was 80% for a specificity of 90% and a positive predictive value of 97.5%. MRI is a reliable examination to confirm the superficial nature of bladder cancer. When MRI and histological examination of a bladder cancer resection specimen are discordant, second look surgery is recommended to treat residual disease, which was present in 60% of cases in the present series.

Spectroscopic analysis of bladder cancer tissues using Fourier transform infrared spectroscopy

NASA Astrophysics Data System (ADS)

Al-Muslet, Nafie A.; Ali, Essam E.

2012-03-01

Bladder cancer is one of the most common cancers in Africa. It takes several days to reach a diagnosis using histological examinations of specimens obtained by endoscope, which increases the medical expense. Recently, spectroscopic analysis of bladder cancer tissues has received considerable attention as a diagnosis technique due to its sensitivity to biochemical variations in the samples. This study investigated the use of Fourier transform infrared (FTIR) spectroscopy to analyze a number of bladder cancer tissues. Twenty-two samples were collected from 11 patients diagnosed with bladder cancer from different hospitals without any pretreatment. From each patient two samples were collected, one normal and another cancerous. FTIR spectrometer was used to differentiate between normal and cancerous bladder tissues via changes in spectra of these samples. The investigations detected obvious changes in the bands of proteins (1650, 1550 cm-1), lipids (2925, 2850 cm-1), and nucleic acid (1080, 1236 cm-1). The results show that FTIR spectroscopy is promising as a rapid, accurate, nondestructive, and easy to use alternative method for identification and diagnosis of bladder cancer tissues.

Increased lung and bladder cancer incidence in adults after in utero and early-life arsenic exposure.

PubMed

Steinmaus, Craig; Ferreccio, Catterina; Acevedo, Johanna; Yuan, Yan; Liaw, Jane; Durán, Viviana; Cuevas, Susana; García, José; Meza, Rodrigo; Valdés, Rodrigo; Valdés, Gustavo; Benítez, Hugo; VanderLinde, Vania; Villagra, Vania; Cantor, Kenneth P; Moore, Lee E; Perez, Saida G; Steinmaus, Scott; Smith, Allan H

2014-08-01

From 1958 to 1970, >100,000 people in northern Chile were exposed to a well-documented, distinct period of high drinking water arsenic concentrations. We previously reported ecological evidence suggesting that early-life exposure in this population resulted in increased mortality in adults from several outcomes, including lung and bladder cancer. We have now completed the first study ever assessing incident cancer cases after early-life arsenic exposure, and the first study on this topic with individual participant exposure and confounding factor data. Subjects included 221 lung and 160 bladder cancer cases diagnosed in northern Chile from 2007 to 2010, and 508 age and gender-matched controls. ORs adjusted for age, sex, and smoking in those only exposed in early life to arsenic water concentrations of ≤110, 110 to 800, and >800 μg/L were 1.00, 1.88 [95% confidence interval (CI), 0.96-3.71], and 5.24 (3.05-9.00; P(trend) < 0.001) for lung cancer, and 1.00, 2.94 (1.29-6.70), and 8.11 (4.31-15.25; P(trend) < 0.001) for bladder cancer. ORs were lower in those not exposed until adulthood. The highest category (>800 μg/L) involved exposures that started 49 to 52 years before, and ended 37 to 40 years before the cancer cases were diagnosed. Lung and bladder cancer incidence in adults was markedly increased following exposure to arsenic in early life, even up to 40 years after high exposures ceased. Such findings have not been identified before for any environmental exposure, and suggest that humans are extraordinarily susceptible to early-life arsenic exposure. Policies aimed at reducing early-life exposure may help reduce the long-term risks of arsenic-related disease. ©2014 American Association for Cancer Research.

A case-control study on the association between bladder cancer and prior bladder calculus.

PubMed

Chung, Shiu-Dong; Tsai, Ming-Chieh; Lin, Ching-Chun; Lin, Herng-Ching

2013-03-15

Bladder calculus is associated with chronic irritation and inflammation. As there is substantial documentation that inflammation can play a direct role in carcinogenesis, to date the relationship between stone formation and bladder cancer (BC) remains unclear. This study aimed to examine the association between BC and prior bladder calculus using a population-based dataset. This case-control study included 2,086 cases who had received their first-time diagnosis of BC between 2001 and 2009 and 10,430 randomly selected controls without BC. Conditional logistic regressions were employed to explore the association between BC and having been previously diagnosed with bladder calculus. Of the sampled subjects, bladder calculus was found in 71 (3.4%) cases and 105 (1.1%) controls. Conditional logistic regression analysis revealed that the odds ratio (OR) of having been diagnosed with bladder calculus before the index date for cases was 3.42 (95% CI = 2.48-4.72) when compared with controls after adjusting for monthly income, geographic region, hypertension, diabetes, coronary heart disease, and renal disease, tobacco use disorder, obesity, alcohol abuse, and schistosomiasis, bladder outlet obstruction, and urinary tract infection. We further analyzed according to sex and found that among males, the OR of having been previously diagnosed with bladder calculus for cases was 3.45 (95% CI = 2.39-4.99) that of controls. Among females, the OR was 3.05 (95% CI = 1.53-6.08) that of controls. These results add to the evidence surrounding the conflicting reports regarding the association between BC and prior bladder calculus and highlight a potential target population for bladder cancer screening.

A review of plan library approaches in adaptive radiotherapy of bladder cancer.

PubMed

Collins, Shane D; Leech, Michelle M

2018-05-01

Large variations in the shape and size of the bladder volume are commonly observed in bladder cancer radiotherapy (RT). The clinical target volume (CTV) is therefore frequently inadequately treated and large isotropic margins are inappropriate in terms of dose to organs at risk (OAR); thereby making adaptive radiotherapy (ART) attractive for this tumour site. There are various methods of ART delivery, however, for bladder cancer, plan libraries are frequently used. A review of published studies on plan libraries for bladder cancer using four databases (Pubmed, Science Direct, Embase and Cochrane Library) was conducted. The endpoints selected were accuracy and feasibility of initiation of a plan library strategy into a RT department. Twenty-four articles were included in this review. The majority of studies reported improvement in accuracy with 10 studies showing an improvement in planning target volume (PTV) and CTV coverage with plan libraries, some by up to 24%. Seventeen studies showed a dose reduction to OARs, particularly the small bowel V45Gy, V40Gy, V30Gy and V10Gy, and the rectal V30Gy. However, the occurrence of no suitable plan was reported in six studies, with three studies showing no significant difference between adaptive and non-adaptive strategies in terms of target coverage. In addition, inter-observer variability in plan selection appears to remain problematic. The additional resources, education and technology required for the initiation of plan library selection for bladder cancer may hinder its routine clinical implementation, with eight studies illustrating increased treatment time required. While there is a growing body of evidence in support of plan libraries for bladder RT, many studies differed in their delivery approach. The advent of the clinical use of the MRI-linear accelerator will provide RT departments with the opportunity to consider daily online adaption for bladder cancer as an alternate to plan library approaches.

Kindlin-2 Expression in Arsenite and Cadmium Transformed Bladder Cancer Cell Lines and in Archival Specimens of Human Bladder Cancer

PubMed Central

Talaat, Sherine; Somji, Seema; Toni, Conrad; Garrett, Scott H.; Zhou, Xu Dong; Sens, Mary Ann; Sens, Donald A.

2011-01-01

Objective The goal of this study was to confirm a microarray study that suggested that Kindlin-2 might play a role in the development and progression of bladder cancer. There has been no previous examination of Kindlin-2 expression in human bladder cancer. Methods A combination of real time PCR, western analysis and immunohistochemistry was used to characterize Kindlin-2 expression in arsenite (As+3) and cadmium (Cd+2) transformed human cell lines, their tumor transplants in immune-compromised mice, and in archival specimens of human bladder and bladder cancer. Results The results show that the Kindlin-2 expression patterns in the cell lines were not duplicated in the tumor tissues. However, it was shown that Kindlin-2 was expressed in the stromal element of all the transplanted tumors and archival specimens of human bladder cancer. It was also shown that a small number of high grade invasive urothelial cancers have focal expression of Kindlin-2 in the tumor cells. Conclusion Kindlin-2 is expressed in the stromal component of most, if not all, human bladder cancers. Kindlin-2 is not expressed in normal urothelium. Kindlin-2 is expressed in a small subset of high grade invasive bladder cancers and may have potential as a prognostic marker for tumor progression. PMID:21624607

Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With mTOR Mutations

ClinicalTrials.gov

2018-06-01

Advanced Malignant Neoplasm; Cervical Squamous Cell Carcinoma; Endometrial Carcinoma; Malignant Uterine Neoplasm; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Malignant Neoplasm; Recurrent Ovarian Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Solid Neoplasm; Stage III Bladder Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIA Cervical Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Breast Cancer; Stage IIIB Cervical Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Breast Cancer; Stage IIIC Ovarian Cancer; Stage IV Breast Cancer; Stage IV Ovarian Cancer; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IVA Bladder Cancer; Stage IVA Cervical Cancer; Stage IVB Bladder Cancer; Stage IVB Cervical Cancer

Liquid Biopsy Analysis of FGFR3 and PIK3CA Hotspot Mutations for Disease Surveillance in Bladder Cancer.

PubMed

Christensen, Emil; Birkenkamp-Demtröder, Karin; Nordentoft, Iver; Høyer, Søren; van der Keur, Kirstin; van Kessel, Kim; Zwarthoff, Ellen; Agerbæk, Mads; Ørntoft, Torben Falck; Jensen, Jørgen Bjerggaard; Dyrskjøt, Lars

2017-06-01

Disease surveillance in patients with bladder cancer is important for early diagnosis of progression and metastasis and for optimised treatment. To develop urine and plasma assays for disease surveillance for patients with FGFR3 and PIK3CA tumour mutations. Droplet digital polymerase chain reaction (ddPCR) assays were developed and tumour DNA from two patient cohorts was screened for FGFR3 and PIK3CA hotspot mutations. One cohort included 363 patients with non-muscle-invasive bladder cancer (NMIBC). The other cohort included 468 patients with bladder cancer undergoing radical cystectomy (Cx). Urine supernatants (NMIBC n=216, Cx n=27) and plasma samples (NMIBC n=39, Cx n=27) from patients harbouring mutations were subsequently screened using ddPCR assays. Progression-free survival, recurrence-free survival, and overall survival were measured. Fisher's exact test, the Wilcoxon rank-sum test and Cox regression analysis were applied. In total, 36% of the NMIBC patients (129/363) and 11% of the Cx patients (44/403) harboured at least one FGFR3 or PIK3CA mutation. Screening of DNA from serial urine supernatants from the NMIBC cohort revealed that high levels of tumour DNA (tDNA) were associated with later disease progression in NMIBC (p=0.003). Furthermore, high levels of tDNA in plasma samples were associated with recurrence in the Cx cohort (p=0.016). A positive correlation between tDNA levels in urine and plasma was observed (correlation coefficient 0.6). The retrospective study design and low volumes of plasma available for analysis were limitations of the study. Increased levels of FGFR3 and PIK3CA mutated DNA in urine and plasma are indicative of later progression and metastasis in bladder cancer. Urine and plasma from patients with bladder cancer may be monitored for diagnosis of progression and metastasis using mutation assays. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Predictive values of urinary bladder tumor markers survivin and soluble-Fas comparison with cystoscopy and bladder tumor antigen.

PubMed

Ganas, V; Kalaitzis, C; Sountoulides, P; Giannakopoulos, S; Touloupidis, S

2012-12-01

The aim of the study was to evaluate the predictive values of two novel urinary markers for bladder cancer: survivin and soluble-Fas (s-Fas). The study included 84 individuals divided in two groups. The first group contained 47 patients, who underwent transurethral bladder tumor resection and the second, control, group 20 patients with non-malignant conditions, who underwent cystoscopy and 17 health volunteers. Fresh, second morning voided urine was collected for measurement of s-Fas, survivin, BTA and for cytology. Sensitivity, specificity, positive and negative predictive values and accuracy were calculated. Bladder tumor patients had significantly higher survivin urine levels in comparison to the controls. Survivin correlated also with the tumor stage. Combination of survivin with BTA had a sensitivity of 86.4% but still lower than that of cystoscopy (97.8%). Only the specificity of the combination between survivin and BTA was higher than that of cystoscopy (86.4% and 75.6%, respectively). Survivin was a better marker for tumor detection than s-Fas and was better enough to discriminate cancer stage. Combination of survivin and BTA had a specificity of 86.4% to exclude bladder malignancy and the combination of s-Fas with survivin and BTA had a sensitivity of 93.6% to detect bladder cancer.

Urinary tract infections and reduced risk of bladder cancer in Los Angeles.

PubMed

Jiang, X; Castelao, J E; Groshen, S; Cortessis, V K; Shibata, D; Conti, D V; Yuan, J-M; Pike, M C; Gago-Dominguez, M

2009-03-10

We investigated the association between urinary tract infections (UTIs) and transitional cell carcinoma of the bladder in a population-based case-control study in Los Angeles covering 1586 cases and age-, gender-, and race-matched neighbourhood controls. A history of bladder infection was associated with a reduced risk of bladder cancer among women (odds ratio (OR), 0.66; 95% confidence interval (CI), 0.46-0.96). No effect was found in men, perhaps due to power limitations. A greater reduction in bladder cancer risk was observed among women with multiple infections (OR, 0.37; 95% CI, 0.18-0.78). Exclusion of subjects with a history of diabetes, kidney or bladder stones did not change the inverse association. A history of kidney infections was not associated with bladder cancer risk, but there was a weak association between a history of other UTIs and slightly increased risk among men. Our results suggest that a history of bladder infection is associated with a reduced risk of bladder cancer among women. Cytotoxicity from antibiotics commonly used to treat bladder infections is proposed as one possible explanation.

Bladder filling variation during conformal radiotherapy for rectal cancer

NASA Astrophysics Data System (ADS)

Sithamparam, S.; Ahmad, R.; Sabarudin, A.; Othman, Z.; Ismail, M.

2017-05-01

Conformal radiotherapy for rectal cancer is associated with small bowel toxicity mainly diarrhea. Treating patients with a full bladder is one of the practical solutions to reduce small bowel toxicity. Previous studies on prostate and cervix cancer patients revealed that maintaining consistent bladder volume throughout radiotherapy treatment is challenging. The aim of this study was to measure bladder volume variation throughout radiotherapy treatment. This study also measured the association between bladder volume changes and diarrhea. Twenty two rectal cancer patients were recruited prospectively. Patients were planned for treatment with full bladder following departmental bladder filling protocol and the planning bladder volume was measured during CT-simulation. During radiotherapy, the bladder volume was measured weekly using cone-beam computed tomography (CBCT) and compared to planning bladder volume. Incidence and severity of diarrhea were recorded during the weekly patient review. There was a negative time trend for bladder volume throughout five weeks treatment. The mean bladder volume decreased 18 % from 123 mL (SD 54 mL) during CT-simulation to 101 mL (SD 71 mL) on the 5th week of radiotherapy, but the decrease is not statistically significant. However, there was a large variation of bladder volume within each patient during treatment. This study showed an association between changes of bladder volume and diarrhea (P = 0.045). In conclusion bladder volume reduced throughout radiotherapy treatment for conformal radiotherapy for rectal cancer and there was a large variation of bladder volume within patients.

Prostate Cancer

MedlinePlus

... man's bladder that produces fluid for semen. Prostate cancer is common among older men. It is rare ... younger than 40. Risk factors for developing prostate cancer include being over 65 years of age, family ...

Replacing cystoscopy by urine markers in the follow-up of patients with low-risk non-muscle-invasive bladder cancer?-An International Bladder Cancer Network project.

PubMed

Schmitz-Dräger, Claudia; Bonberg, Nadine; Pesch, Beate; Todenhöfer, Tilman; Sahin, Sevim; Behrens, Thomas; Brüning, Thomas; Schmitz-Dräger, Bernd J

2016-10-01

Numerous molecular urine markers for the diagnosis of bladder cancer have been developed and evaluated mostly in case-control settings through the past decades. However, despite all efforts none of them has been included into clinical decision-making and guideline recommendations until today. The aim of this retrospective longitudinal analysis was to investigate if a molecular marker might be able to replace cystoscopy as a primary examination in diagnosis and follow-up of patients with pTa grade 1-2 bladder cancer. Totally 36 patients (32 men) with pTa grade 1-2 bladder cancer underwent 232 follow-up examinations including urine analysis, cytology, immunocytology (uCyt+), and urethrocystoscopy (UC). Mean age at study entry was 63 years. Patients were observed through a median follow-up interval of 3.8 years. In summary, 47 Transurethral Resection of Bladder Tumors (TURB) procedures were indicated based upon a positive UC (44) or as re-TURB (3) and 33 tumors (plus 1 case of pTa G0) were histopathologically confirmed. Although uCyt+was positive in 12/13 primary tumors (92.3%), sensitivity dropped to 13/20 (65%) in tumor recurrence presumably because of their smaller size. Urine cytology had a sensitivity and a specificity of 30.3% and 94.9%, respectively, but did not improve the sensitivity of uCyt+alone. If UC was based upon a positive uCyt+test, 8/33 tumors (24.2%) would have been overlooked or diagnosed late. In contrast, 173 UCs (74%) would have been saved and 5 presumably unnecessary TURB procedures would not have been indicated. This longitudinal study suggests a potential of molecular urine tests in replacing cystoscopy in the follow-up of patients with pTa G1-2 bladder cancer. The use of additional markers might further improve sensitivity of urine testing. A prospective randomized study has been initiated to prospectively investigate the performance of a marker panel against UC. Copyright © 2016 Elsevier Inc. All rights reserved.

Quality of life in women undergoing urinary diversion for bladder cancer: results of a multicenter study among long-term disease-free survivors.

PubMed

Gacci, Mauro; Saleh, Omar; Cai, Tommaso; Gore, John L; D'Elia, Carolina; Minervini, Andrea; Masieri, Lorenzo; Giannessi, Claudia; Lanciotti, Michele; Varca, Virginia; Simonato, Alchiede; Serni, Sergio; Carmignani, Giorgio; Carini, Marco

2013-03-12

Women undergoing radical cystectomy (RC) and urinary diversion for bladder cancer experience substantial limitations in health-related quality of life (HRQOL). However, the level of discomfort caused by different urinary diversion has been never evaluated in long term survivors. The aim of this multicenter study is to evaluate differences in HRQOL among recurrence-free women undergoing cutaneous ureterostomy (CUS), Bricker's ileal conduit (BK-IC) and Orthotopic neobladder VIP (ONB-VIP) in disease-free females treated with radical cystectomy (RC), with long-term follow up (mean 60.1 months; range 36-122 months). All consecutively treated female patients from two urological institutions who underwent RC and urinary diversion from January 2000 to December 2008, with no evidence of tumor recurrence at a minimum follow up of 36 months, were included. Patients received the European Organisation for Research and Treatment of Cancer (EORTC) generic (QLQ-C30) and bladder cancer-specific instruments (QLQ-BLM30) and the Functional Assessment of Cancer Therapy for Bladder Cancer (FACT-BL). Clinical data and questionnaire results were analyzed in order to evaluate the HRQOL differences among diversion groups. We identified 37 females (median age: 68, range 45-82 years), including 12 status-post CUS, 16 who underwent BK-IC, and 9 who underwent ONB-VIP. Most were healthy (24/37 with no comorbidities, 4/37 Charlson 1-2, 9/37 Charlson 3 or greater - we didn't considered bladder cancer in Charlson evaluation because bladder cancer was the main inclusion criteria). Women undergoing CUS endorsed worse FACT-BL scores compared with BK-IC and ONB-VIP patients, worse HRQOL regarding physical and emotional well-being (p=0.008 and p=0.02, respectively), and a trend toward worse EORTC QLQ-C30 scores for appetite loss and fatigue (p=0.05 for both). In our study long-term disease-free females treated with CUS endorsed worse HRQOL compared with women who underwent BK-IC or ONB-VIP, mostly due to worse physical and emotional perception of their body image.

Urinary tract infection-like symptom is associated with worse bladder cancer outcomes in the Medicare population: Implications for sex disparities.

PubMed

Richards, Kyle A; Ham, Sandra; Cohn, Joshua A; Steinberg, Gary D

2016-01-01

To determine the time to bladder cancer diagnosis from initial infection-like symptoms and its impact on cancer outcomes. Using Surveillance, Epidemiology and End Results-Medicare, we designed a retrospective cohort study identifying beneficiaries aged ≥ 66 years diagnosed with bladder cancer from 2007 to 2009. Patients were required to have a hematuria or urinary tract infection claim within 1 year of bladder cancer diagnosis (n = 21 216), and have 2 years of prior Medicare data (n = 18 956) without any precedent hematuria, bladder cancer or urinary tract infection claims (n = 12 195). The number of days to bladder cancer diagnosis was measured, as well as the impact of sex and presenting symptom on time to diagnosis, pathology, and oncological outcomes. The mean time to bladder cancer diagnosis was 72.2 days in women versus 58.9 days in men (P < 0.001). A logistic regression model identified the greatest predictors of ≥ pT2 pathology were both women (odds ratio 2.08, 95% confidence interval 1.70-2.55) and men (odds ratio 1.71, 95% confidence interval 1.49-1.97) presenting with urinary tract infection. Cox proportional hazards analysis identified an increased risk of mortality from bladder cancer and all causes in women presenting with urinary tract infection (hazard ratio 1.37, 95% confidence interval 1.10-1.71, and hazard ratio 1.47, 95% confidence interval 1.28-1.69) compared with women with hematuria. Women have a longer interval from urinary tract infection to diagnosis of bladder cancer. Urinary tract infection presentation can adversely affect time to diagnosis, pathology and survival. Time to diagnosis seems not to be an independent predictor of bladder cancer outcomes. © 2015 The Japanese Urological Association.

Possible distinct molecular carcinogenic pathways for bladder cancer in Ukraine, before and after the Chernobyl disaster.

PubMed

Morimura, Keiichirou; Romanenko, Alina; Min, Wei; Salim, Elsayed I; Kinoshita, Anna; Wanibuchi, Hideki; Vozianov, Alexander; Fukushima, Shoji

2004-04-01

After the Chernobyl accident in 1986, the incidence of urinary bladder cancers in the Ukraine increased gradually from 26.2 to 43.3 per 100,000 people between 1986 and 2001. In the areas of low level but persistent cesium-137 (137Cs) radio-contamination, a unique atypical radiation-related urinary bladder cystitis named 'Chernobyl cystitis', a possible pre-neoplastic condition in humans, has been detected. We have previously documented high incidences of bladder lesions, including severe dysplasias and/or carcinoma in situ, in association with this cystitis and correlating with oxidative DNA damage. To further investigate the molecular mechanisms underlying bladder carcinogenesis with this specific etiology, mutation analysis of p53 gene (exon 5-8) was performed for 11 and 18 paraffin-embedded bladder cancers in Ukrainians, respectively collected before and after the Chernobyl disaster. DNAs were extracted and subjected to nested PCR-single-strand conformational polymorphism analysis followed by direct DNA sequencing, as well as p53 immunohistochemistry (IHC). The incidences of p53 gene mutation were 54.5 and 16.7% for before and after the Chernobyl disaster, respectively, the difference being statistically significant. Also a tendency for higher p53 IHC score was apparent in the earlier group of lesions. No significant difference was noted for the proportions of historical types. These results point to possible distinct molecular carcinogenic pathways of bladder cancer formation, before and after the Chernobyl disaster, on the basis of variation in p53 gene alteration.

Effect of routine repeat transurethral resection for superficial bladder cancer: a long-term observational study.

PubMed

Grimm, Marc-Oliver; Steinhoff, Christine; Simon, Xenia; Spiegelhalder, Philipp; Ackermann, Rolf; Vogeli, Thomas Alexander

2003-08-01

We determined the long-term outcome in patients with superficial bladder cancer (Ta and T1) undergoing routine second transurethral bladder tumor resection (ReTURB) in regard to recurrence and progression. We performed an inception cohort study of 124 consecutive patients with superficial bladder cancer undergoing transurethral resection and routine ReTURB (83) between November 1993 and October 1995 at a German university hospital. Immediately after transurethral resection all lesions were documented on a designed bladder map. ReTURB of the scar from initial resection and other suspicious lesions was performed at a mean of 7 weeks. Patients were followed until recurrence or death, or a minimum of 5 years. Residual tumor was found in 33% of all ReTURB cases, including 27% of Ta and 53% of T1 disease, and in 81% at the initial resection site. Five of the 83 patients underwent radical cystectomy due to ReTURB findings. The estimated risk of recurrence after years 1 to 3 was 18%, 29% and 32%, respectively. After 5 years 63% of the patients undergoing ReTURB were still disease-free (mean recurrence-free survival 62 months, median 87). Progression to muscle invasive disease was observed in only 2 patients (3%) after a mean observation of 61 months. These data suggest a favorable outcome regarding recurrence and progression in patients with superficial bladder cancer who undergo ReTURB. ReTURB is suggested at least in those at high risk when bladder preservation is intended.

Pretreatment Neutrophil-Lymphocyte Ratio as a Predictor in Bladder Cancer and Metastatic or Unresectable Urothelial Carcinoma Patients: a Pooled Analysis of Comparative Studies.

PubMed

Wu, Shuiqing; Zhao, Xiaokun; Wang, Yinhuai; Zhong, Zhaohui; Zhang, Lei; Cao, Jian; Ai, Kai; Xu, Ran

2018-01-01

Emerging studies have shown that the neutrophil-lymphocyte ratio (NLR) is a potential predictor in various tumors. Our study was conducted to assess the prognostic value of the pretreatment NLR in bladder cancer and metastatic or unresectable urothelial carcinoma (mUC or uUC) patients up to July 2017. The correlation between the pretreatment NLR and pathological characteristics was also evaluated in bladder cancer patients. The hazard ratio (HR) and odds ratio (OR) with the 95% confidence interval (CI) were extracted or calculated from the included studies for further pooled analysis. A total of 21 studies were included in a pooled analysis. The pooled results indicated that a high pretreatment NLR was associated with reduced overall survival (OS) (HR=1.27, 95% CI=1.12-1.43), relapse-free survival (RFS) (HR=1.41, 95% CI=1.23-1.60), progression-free survival (PFS) (HR=1.75, 95% CI=1.36-2.15), disease-specific survival (DSS) and cancer-specific survival (CSS) (HR=1.27, 95% CI=1.19-1.35) in the bladder cancer patients. Additionally, an elevated pretreatment NLR suggested a worse OS rate in the mUC or uUC patients (HR=1.63, 95% CI=1.34-1.91). The pooled ORs and 95% CIs showed that a high pretreatment NLR could be a risk indicator for certain pathological features, such as lymphovascular invasion, a positive margin status and advanced tumor stage. our results showed that a high pretreatment NLR predicted poor prognosis in bladder cancer, mUC and uUC patients. © 2018 The Author(s). Published by S. Karger AG, Basel.

Enhanced inhibition of urinary bladder cancer growth and muscle invasion by allyl isothiocyanate and celecoxib in combination

PubMed Central

Zhang, Yuesheng

2013-01-01

Allyl isothiocyanate (AITC) occurs in cruciferous vegetables that are commonly consumed by humans and has been shown to inhibit urinary bladder cancer growth and progression in previous preclinical studies. However, AITC does not significantly modulate cyclooxygenase-2 (Cox-2), whose oncogenic activity has been well documented in bladder cancer and other cancers. Celecoxib is a selective Cox-2 inhibitor and has been widely used for treatment of several diseases. Celecoxib has also been evaluated in bladder cancer patients, but its efficacy against bladder cancer as a single agent remains unclear. In a syngeneic rat model of orthotopic bladder cancer, treatment of the animals with the combination of AITC and celecoxib at low dose levels (AITC at 1mg/kg and celecoxib at 10mg/kg) led to increased or perhaps synergistic inhibition of bladder cancer growth and muscle invasion, compared with each agent used alone. The combination regime was also more effective than each single agent in inhibiting microvessel formation and stimulating microvessel maturation in the tumor tissues. The anticancer efficacy of the combination regime was associated with depletion of prostaglandin E2, a key downstream signaling molecule of Cox-2, caspase activation and downregulation of vascular endothelial growth factor in the tumor tissues. These data show that AITC and celecoxib complement each other for inhibition of bladder cancer and provide a novel combination approach for potential use for prevention or treatment of human bladder cancer. PMID:23946495

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

PubMed

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.

Biomarkers in bladder cancer: present status and perspectives.

PubMed

Kim, Wun-Jae; Park, Soongang; Kim, Yong-June

2007-03-27

Bladder cancers are a mixture of heterogeneous cell populations, and numerous factors are likely to be involved in dictating their recurrence, progression and the patient's survival. For any candidate prognostic marker to have considerable clinical relevance, it must add some predictive capacity beyond that offered by conventional clinical and pathologic parameters. Here, the current situation in bladder cancer research with respect to identification of suitable prognostic markers is reviewed. A number of individual molecular markers that might predict bladder cancer recurrence and progression have been identified but many are not sufficiently sensitive or specific for the whole spectrum of bladder cancer diseases seen in routine clinical practice. These limitations have led to interest in other molecular parameters that could enable more accurate prognosis for bladder cancer patients. Of particular interest is the epigenetic silencing of tumor suppressor genes. Since the methylation of these genes can correlate with a poor prognosis, the methylation profile may represent a new bio-marker that indicates the risk of transitional cell carcinoma development. In addition, bladder cancer research is likely to be revolutionized by high-throughput molecular technologies, which allow rapid and global gene expression analysis of thousands of tumor samples. Initial studies employing these technologies have considerably expanded our ability to classify bladder cancers with respect to their survivability. Future microarray analyses are likely to reveal particular gene expression signatures that predict the likelihood of bladder cancer progression and recurrence, as well as patient's survival and responsiveness to different anti-cancer therapies, with great specificity and sensitivity.

Does uneven geographic distribution of urologists effect bladder and prostate cancers mortality? National health insurance data in Korea from 2007-2011.

PubMed

Kim, Jae Heon; Sun, Hwa Yeon; Kim, Hyun Jung; Ko, Young Myoung; Chun, Dong-Il; Park, Jae Young

2017-09-12

The relationship between distribution of urologists and mortality of bladder and prostate cancers has not been clearly established. The aim of this study was to investigate the relationship between uneven distribution of urologists and urologic cancer specific mortality at country level. Data from the National Health Insurance Service and National Statistical Office in Korea from 2007 to 2011 were analyzed in this ecological study. Univariate and multivariable regression analyses were performed to determine risk factors for age standardized mortality rates (ASMR) of bladder and prostate cancers. Linear regression analysis showed a markedly ( p < 0.001) uneven distribution of urologists between metropolitan and non-metropolitan areas. There was no significant difference in cancer specific ASMRs for either bladder cancer or prostate cancer. Univariate analysis after adjusting for time showed that country area, urologist density, and income were significant factors affecting bladder cancer incidence ( p < 0.001, p = 0.013, and p < 0.001, respectively). It also showed that the number of training hospitals was a significant factor for prostate cancer incidence ( p = 0.002). Although country area showed borderline significance ( p = 0.056) for ASMR of bladder cancer, urologist density was not related to ASMR of bladder cancer or prostate cancer. Although there was a marked difference in urologist density between metropolitan and non-metropolitan areas for these years analyzed, mortality rates of bladder and prostate cancers were not significantly affected by country area or urologist density.

Does uneven geographic distribution of urologists effect bladder and prostate cancers mortality? National health insurance data in Korea from 2007–2011

PubMed Central

Kim, Jae Heon; Sun, Hwa Yeon; Kim, Hyun Jung; Ko, Young Myoung; Chun, Dong-Il; Park, Jae Young

2017-01-01

The relationship between distribution of urologists and mortality of bladder and prostate cancers has not been clearly established. The aim of this study was to investigate the relationship between uneven distribution of urologists and urologic cancer specific mortality at country level. Data from the National Health Insurance Service and National Statistical Office in Korea from 2007 to 2011 were analyzed in this ecological study. Univariate and multivariable regression analyses were performed to determine risk factors for age standardized mortality rates (ASMR) of bladder and prostate cancers. Linear regression analysis showed a markedly (p < 0.001) uneven distribution of urologists between metropolitan and non-metropolitan areas. There was no significant difference in cancer specific ASMRs for either bladder cancer or prostate cancer. Univariate analysis after adjusting for time showed that country area, urologist density, and income were significant factors affecting bladder cancer incidence (p < 0.001, p = 0.013, and p < 0.001, respectively). It also showed that the number of training hospitals was a significant factor for prostate cancer incidence (p = 0.002). Although country area showed borderline significance (p = 0.056) for ASMR of bladder cancer, urologist density was not related to ASMR of bladder cancer or prostate cancer. Although there was a marked difference in urologist density between metropolitan and non-metropolitan areas for these years analyzed, mortality rates of bladder and prostate cancers were not significantly affected by country area or urologist density. PMID:29029431

Novel bifunctional anthracycline and nitrosourea chemotherapy for human bladder cancer: analysis in a preclinical survival model.

PubMed

Glaves, D; Murray, M K; Raghavan, D

1996-08-01

A hybrid drug [N-2-chloroethylnitrosoureidodaunorubicin (AD312)] that combines structural and functional features of both anthracyclines and nitrosoureas was evaluated in a preclinical survival model of human bladder cancer. To measure the therapeutic activity of AD312, UCRU-BL13 transitional cell carcinoma cells were grown as xenografts in nude mice, and tumor growth rates were compared after i.v. administration of the drug at three dose levels. AD312 treatment at 45 and 60 mg/kg achieved 7-10-fold inhibition of tumor growth and increased host survival by 156 and 249%, respectively. Doses of 60 mg/kg showed optimal therapeutic efficacy, with sustained tumor growth inhibition, an over 2-fold increase in life span, and 40% of mice tumor free ("cured") at 120 days. Tumors were unresponsive to maximum tolerated doses of doxorubicin, a standard anthracycline used as a single agent and in combination therapies for bladder cancer. 1,3-Bis-[2-chloroethyl]-1-nitrosourea was used as a control for the apparently enhanced response of human tumors in murine hosts to nitrosoureas. 1, 3-Bis-[2-chloroethyl]-1-nitrosourea administered in three injections of 20 mg/kg did not cure mice but temporarily inhibited tumor growth by 70% and prolonged survival by 55%; its activity in this model suggests that it may be included in the repertoire of alkylating agents currently used for treatment of bladder cancers. AD312 showed increased antitumor activity with less toxicity than doxorubicin, and its bifunctional properties provide the opportunity for simultaneous treatment of individual cancer cells with two cytotoxic modalities as well as treatment of heterogeneous populations typical of bladder cancers. This novel cytotoxic drug cured doxorubicin-refractory disease and should be investigated for the clinical management of bladder cancer.

Biomarker in Cisplatin-Based Chemotherapy for Urinary Bladder Cancer.

PubMed

Ecke, Thorsten H

2015-01-01

The treatment of metastasized bladder cancer has been evolving during recent years. Cisplatin based chemotherapy combinations are still gold standard in the treatment of advanced and metastasized bladder cancer. But new therapies are approaching. Based to this fact biological markers will become more important for decisions in bladder cancer treatment. A systematic MEDLINE search of the key words "cisplatin", "bladder cancer", "DNA marker", "protein marker", "methylation biomarker", "predictive marker", "prognostic marker" has been made. This review aims to highlight the most relevant clinical and experimental studies investigating markers for metastasized transitional carcinoma of the urothelium treated by cisplatin based regimens.

Cabozantinib-s-malate and Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Genitourinary Tumors

ClinicalTrials.gov

2018-04-02

Clear Cell Renal Cell Carcinoma; Metastatic Malignant Neoplasm in the Bone; Metastatic Penile Carcinoma; Renal Pelvis Urothelial Carcinoma; Squamous Cell Carcinoma of the Penis; Stage III Bladder Adenocarcinoma AJCC v6 and v7; Stage III Bladder Squamous Cell Carcinoma AJCC v6 and v7; Stage III Bladder Urothelial Carcinoma AJCC v6 and v7; Stage III Penile Cancer AJCC v7; Stage III Renal Cell Cancer AJCC v7; Stage III Renal Pelvis Cancer AJCC v7; Stage III Ureter Cancer AJCC v7; Stage III Urethral Cancer AJCC v7; Stage IIIa Penile Cancer AJCC v7; Stage IIIb Penile Cancer AJCC v7; Stage IV Bladder Adenocarcinoma AJCC v7; Stage IV Bladder Squamous Cell Carcinoma AJCC v7; Stage IV Bladder Urothelial Carcinoma AJCC v7; Stage IV Penile Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7; Stage IV Renal Pelvis Cancer AJCC v7; Stage IV Ureter Cancer AJCC v7; Stage IV Urethral Cancer AJCC v7; Ureter Urothelial Carcinoma; Urethral Urothelial Carcinoma

Identification of Novel Gene Targets and Putative Regulators of Arsenic-Associated DNA Methylation in Human Urothelial Cells and Bladder Cancer

PubMed Central

Rager, Julia E.; Miller, Sloane; Tulenko, Samantha E.; Smeester, Lisa; Ray, Paul D.; Yosim, Andrew; Currier, Jenna M.; Ishida, María C.; González-Horta, Maria del Carmen; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Gutiérrez-Torres, Daniela S.; Drobná, Zuzana; Del Razo, Luz M.; García-Vargas, Gonzalo G.; Kim, William Y.; Zhou, Yi-Hui; Wright, Fred A.; Stýblo, Miroslav; Fry, Rebecca C.

2016-01-01

There is strong epidemiologic evidence linking chronic exposure to inorganic arsenic (iAs) to a myriad of adverse health effects, including cancer of the bladder. The present study set out to identify DNA methylation patterns associated with iAs and its metabolites in exfoliated urothelial cells (EUCs) that originate primarily from the urinary bladder, one of the targets of arsenic (As)-induced carcinogenesis. Genome-wide, gene-specific promoter DNA methylation levels were assessed in EUCs from 46 residents of Chihuahua, Mexico, and the relationship was examined between promoter methylation profiles and the intracellular concentrations of total As (tAs) and As species. A set of 49 differentially methylated genes was identified with increased promoter methylation associated with EUC tAs, iAs, and/or monomethylated As (MMAs) enriched for their roles in metabolic disease and cancer. Notably, no genes had differential methylation associated with EUC dimethylated As (DMAs), suggesting that DMAs may influence DNA methylation-mediated urothelial cell responses to a lesser extent than iAs or MMAs. Further analysis showed that 22 of the 49 As-associated genes (45%) are also differentially methylated in bladder cancer tissue identified using The Cancer Genome Atlas repository. Both the As- and cancer-associated genes are enriched for the binding sites of common transcription factors known to play roles in carcinogenesis, demonstrating a novel potential mechanistic link between iAs exposure and bladder cancer. PMID:26039340

Atezolizumab in Treating Patients With Recurrent BCG-Unresponsive Non-muscle Invasive Bladder Cancer

ClinicalTrials.gov

2018-06-25

Recurrent Bladder Urothelial Carcinoma; Stage 0a Bladder Urothelial Carcinoma AJCC v6 and v7; Stage 0is Bladder Urothelial Carcinoma AJCC v6 and v7; Stage I Bladder Cancer With Carcinoma In Situ; Stage I Bladder Urothelial Carcinoma AJCC v6 and v7

Oncogenic role of fibroblast growth factor receptor 3 in tumorigenesis of urinary bladder cancer.

PubMed

Pandith, Arshad A; Shah, Zafar A; Siddiqi, Mushtaq A

2013-05-01

Bladder cancer is the second most common genitourinary tumor and constitutes a very heterogeneous disease. Molecular and pathologic studies suggest that low-grade noninvasive and high-grade invasive urothelial cell carcinoma (UCC) arise via distinct pathways. Low-grade noninvasive UCC represent the majority of tumors at presentation. A high proportion of patients with low-grade UCC develop recurrences but usually with no progression to invasive disease. At presentation, a majority of the bladder tumors (70%-80%) are low-grade noninvasive (pTa). Several genetic changes may occur in bladder cancer, but activating mutations in the fibroblast growth factor receptor 3 (FGFR3) genes are the most common and most specific genetic abnormality in bladder cancer. Interestingly, these mutations are associated with bladder tumors of low stage and grade, which makes the FGFR3 mutation the first marker that can be used for diagnosis of noninvasive bladder tumors. Since the first report of FGFR3 involvement in bladder tumors, numerous studies have been conducted to understand its function and thereby confirm the oncogenic role of this receptor particularly in noninvasive groups. Efforts are on to exploit this receptor as a therapeutic target, which holds much promise in the treatment of bladder cancer, particularly low-grade noninvasive tumors. Further studies need to explore the potential use of FGFR3 mutations in bladder cancer diagnosis, prognosis, and in surveillance of patients with bladder cancer. This review focuses on the role of FGFR3 in bladder tumors in the backdrop of various studies published. Copyright © 2013 Elsevier Inc. All rights reserved.

Prospective comparison of molecular signatures in urothelial cancer of the bladder and the upper urinary tract--is there evidence for discordant biology?

PubMed

Krabbe, Laura-Maria; Lotan, Yair; Bagrodia, Aditya; Gayed, Bishoy A; Darwish, Oussama M; Youssef, Ramy F; Bolenz, Christian; Sagalowsky, Arthur I; Raj, Ganesh V; Shariat, Shahrokh F; Kapur, Payal; Margulis, Vitaly

2014-04-01

Upper tract urothelial carcinoma is rare and less well studied than bladder cancer. It remains questionable if findings in bladder cancer can safely be extrapolated to upper tract urothelial carcinoma. We prospectively evaluate molecular profiles of upper tract urothelial carcinoma and bladder cancer using a cell cycle biomarker panel. Immunohistochemical staining for p21, p27, p53, cyclin E and Ki-67 was prospectively performed for 96 patients with upper tract urothelial carcinoma and 159 patients with bladder cancer with nonmetastatic high grade urothelial carcinoma treated with extirpative surgery. Data were compared between the groups according to pathological stage. Primary outcome was assessment of differences in marker expression. Secondary outcome was difference in survival according to marker status. During a median followup of 22.0 months 31.2% of patients with upper tract urothelial carcinoma and 28.3% of patients with bladder cancer had disease recurrence, and 20.8% and 27.7% died of upper tract urothelial carcinoma and bladder cancer, respectively. The number of altered markers was not significantly different between the study groups. Overall 34 patients (35.4%) with upper tract urothelial carcinoma and 62 (39.0%) with bladder cancer had an unfavorable marker score (more than 2 markers altered). There were no significant differences between upper tract urothelial carcinoma and bladder cancer in the alteration status of markers, the number of altered markers and biomarker score when substratified by pathological stage. There were no significant differences in survival outcomes between patients with upper tract urothelial carcinoma and those with bladder cancer according to the number of altered markers and biomarker score. Our results demonstrate the molecular similarity of upper tract urothelial carcinoma and bladder cancer in terms of cell cycle and proliferative tissue markers. These findings have important implications and support the further extrapolation of treatment paradigms established in bladder cancer to upper tract urothelial carcinoma. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Intake of fruit and vegetables and risk of bladder cancer: a dose-response meta-analysis of observational studies.

PubMed

Yao, Baodong; Yan, Yujie; Ye, Xianwu; Fang, Hong; Xu, Huilin; Liu, Yinan; Li, Sheran; Zhao, Yanping

2014-12-01

Observational studies suggest an association between fruit and vegetables intake and risk of bladder cancer, but the results are controversial. We therefore summarized the evidence from observational studies in categorical, linear, and nonlinear, dose-response meta-analysis. Pertinent studies were identified by searching EMBASE and PubMed from their inception to August 2013. Thirty-one observational studies involving 12,610 cases and 1,121,649 participants were included. The combined rate ratio (RR, 95 % CI) of bladder cancer for the highest versus lowest intake was 0.83 (0.69-0.99) for total fruit and vegetables, 0.81 (0.70-0.93) for total vegetables, 0.77 (0.69-0.87) for total fruit, 0.84 (0.77-0.91) for cruciferous vegetables, 0.79 (0.68-0.91) for citrus fruits, and 0.74 (0.66-0.84) for yellow-orange vegetables. Subgroup analysis showed study design and gender as possible sources of heterogeneity. A nonlinear relationship was found of citrus fruits intake with risk of bladder cancer (P for nonlinearity = 0.018), and the RRs (95 % CI) of bladder cancer were 0.87 (0.78-0.96), 0.80 (0.67-0.94), 0.79 (0.66-0.94), 0.79 (0.65-0.96), and 0.79 (0.64-0.99) for 30, 60, 90, 120, and 150 g/day. A nonlinear relationship was also found of yellow-orange vegetable intake with risk of bladder cancer risk (P for nonlinearity = 0.033). Some evidence of publication bias was observed for fruit, citrus fruits, and yellow-orange vegetables. This meta-analysis supports the hypothesis that intakes of fruit and vegetables may reduce the risk of bladder cancer. Future well-designed studies are required to confirm this finding.

Exercise Decreases and Smoking Increases Bladder Cancer Mortality

PubMed Central

Liss, Michael A.; White, Martha; Natarajan, Loki; Parsons, J. Kellogg

2018-01-01

Modifiable lifestyle factors play an important role regarding the development and outcomes in solid tumors. Whereas smoking has been attributed to bladder cancer and cessation leads to better outcome, we show that exercise may provide similar benefits regarding bladder cancer mortality Background The aim of this study was to investigate modifiable lifestyle factors of smoking, exercise, and obesity with bladder cancer mortality. Patients and Methods We used mortality-linked data from the National Health Information Survey from 1998 through 2006. The primary outcome was bladder cancer-specific mortality. The primary exposures were self-reported smoking status (never- vs. former vs. current smoker), self-reported exercise (dichotomized as “did no exercise” vs. “light, moderate, or vigorous exercise in ≥ 10-minute bouts”), and body mass index. We utilized multivariable adjusted Cox proportional hazards regression models, with delayed entry to account for age at survey interview. Results Complete data were available on 222,163 participants, of whom 96,715 (44%) were men and 146,014 (66%) were non-Hispanic whites, and among whom we identified 83 bladder cancer-specific deaths. In multivariate analyses, individuals who reported any exercise were 47% less likely (adjusted hazard ratio [HRadj], 0.53; 95% confidence interval [CI], 0.29–0.96; P = .038) to die of bladder cancer than “no exercise”. Compared with never-smokers, current (HRadj, 4.24; 95% CI, 1.89–9.65; P = .001) and former (HRadj, 2.95; 95% CI, 1.50–5.79; P = .002) smokers were 4 and 3 times more likely, respectively, to die of bladder cancer. There were no significant associations of body mass index with bladder cancer mortality. Conclusion Exercise decreases and current smoking increases the risk of bladder cancer-specific mortality. These data suggest that exercise and smoking cessation interventions may reduce bladder cancer death. PMID:28007367

Trigriluzole With Nivolumab and Pembrolizumab in Treating Patients With Metastatic or Unresectable Solid Malignancies or Lymphoma

ClinicalTrials.gov

2018-05-23

Lymphoma; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Metastatic Renal Cell Cancer; Recurrent Bladder Carcinoma; Recurrent Classical Hodgkin Lymphoma; Recurrent Head and Neck Squamous Cell Carcinoma; Recurrent Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Renal Cell Carcinoma; Stage III Bladder Cancer; Stage III Lymphoma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage III Renal Cell Cancer; Stage III Skin Melanoma; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Skin Melanoma; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Bladder Cancer; Stage IV Lymphoma; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IVA Bladder Cancer; Stage IVB Bladder Cancer; Unresectable Head and Neck Squamous Cell Carcinoma; Unresectable Solid Neoplasm

High expression of insulin receptor on tumour-associated blood vessels in invasive bladder cancer predicts poor overall and progression-free survival.

PubMed

Roudnicky, Filip; Dieterich, Lothar C; Poyet, Cedric; Buser, Lorenz; Wild, Peter; Tang, Dave; Camenzind, Peter; Ho, Chien Hsien; Otto, Vivianne I; Detmar, Michael

2017-06-01

Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival. Furthermore, increased expression of the INSR ligand IGF-2 in invasive bladder cancers was associated with reduced overall survival. INSR may therefore represent a novel biomarker to predict cancer progression. Mechanistically, we observed pronounced hypoxia in human bladder cancer tissue, and found a positive correlation between the expression of the hypoxia marker gene GLUT1 and vascular INSR expression, indicating that hypoxia drives INSR expression in tumour-associated blood vessels. In line with this, exposure of cultured BECs and human bladder cancer cell lines to hypoxia led to increased expression of INSR and IGF-2, respectively, and IGF-2 increased BEC migration through the activation of INSR in vitro. Taken together, we identified vascular INSR expression as a potential biomarker for progression in bladder cancer. Furthermore, our data suggest that IGF-2/INSR mediated paracrine crosstalk between bladder cancer cells and endothelial cells is functionally involved in tumour angiogenesis and may thus represent a new therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Endometrial Cancer Prevention

MedlinePlus

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... Heart disease. Head and neck cancers . Lung cancer . Bladder cancer . Pancreatic cancer . It is not known if the ...

Attenuated XPC Expression Is Not Associated with Impaired DNA Repair in Bladder Cancer

PubMed Central

Naipal, Kishan A. T.; Raams, Anja; Bruens, Serena T.; Brandsma, Inger; Verkaik, Nicole S.; Jaspers, Nicolaas G. J.; Hoeijmakers, Jan H. J.; van Leenders, Geert J. L. H.; Pothof, Joris; Kanaar, Roland; Boormans, Joost; van Gent, Dik C.

2015-01-01

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. PMID:25927440

Bladder Cancer

MedlinePlus

... have an elevated risk of developing bladder cancer. Chronic bladder inflammation. Chronic or repeated urinary infections or inflammations (cystitis), ... the world, squamous cell carcinoma is linked to chronic bladder inflammation caused by the parasitic infection known as schistosomiasis. ...

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

PubMed Central

Quirk, Jeffrey T; Li, Qiang; Natarajan, Nachimuthu; Mettlin, Curtis J; Cummings, K Michael

2004-01-01

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.

OK-432 Suppresses Proliferation and Metastasis by Tumor Associated Macrophages in Bladder Cancer.

PubMed

Tian, Yuan-Feng; Tang, Kun; Guan, Wei; Yang, Tao; Xu, Hua; Zhuang, Qian-Yuan; Ye, Zhang-Qun

2015-01-01

OK-432, a Streptococcus-derived anticancer immunotherapeutic agent, has been applied in clinic for many years and achieved great progress in various cancers. In the present study, we investigated its anticancer effect on bladder cancer through tumor associated macrophages (TAMs). MTS assay validated OK-432 could inhibit proliferation in both T24 and EJ bladder cell lines. OK-432 also induced apoptosis of bladder cancer cells in vitro. Consequently, we demonstrated that OK-432 could suppress the bladder cancer cells migration and invasion by altering the EMT-related factors. Furthermore, using SD rat model, we revealed that OK-432 inhibited tumor growth, suppressed PCNA expression and inhibited metastasis in vivo. Taken together, these findings strongly suggest that OK-432 inhibits cell proliferation and metastasis through inducing macrophages to secret cytokines in bladder cancer.

Suppression of progranulin expression inhibits bladder cancer growth and sensitizes cancer cells to cisplatin.

PubMed

Buraschi, Simone; Xu, Shi-Qiong; Stefanello, Manuela; Moskalev, Igor; Morcavallo, Alaide; Genua, Marco; Tanimoto, Ryuta; Birbe, Ruth; Peiper, Stephen C; Gomella, Leonard G; Belfiore, Antonino; Black, Peter C; Iozzo, Renato V; Morrione, Andrea

2016-06-28

We have recently demonstrated a critical role for progranulin in bladder cancer. Progranulin contributes, as an autocrine growth factor, to the transformed phenotype by modulating Akt-and MAPK-driven motility, invasion and anchorage-independent growth. Progranulin also induces F-actin remodeling by interacting with the F-actin binding protein drebrin. In addition, progranulin is overexpressed in invasive bladder cancer compared to normal tissue controls, suggesting that progranulin might play a key role in driving the transition to the invasive phenotype of urothelial cancer. However, it is not established whether targeting progranulin could have therapeutic effects on bladder cancer. In this study, we stably depleted urothelial cancer cells of endogenous progranulin by shRNA approaches and determined that progranulin depletion severely inhibited the ability of tumorigenic urothelial cancer cells to migrate, invade and grow in anchorage-independency. We further demonstrate that progranulin expression is critical for tumor growth in vivo, in both xenograft and orthotopic tumor models. Notably, progranulin levels correlated with response to cisplatin treatment and were upregulated in bladder tumors. Our data indicate that progranulin may constitute a novel target for therapeutic intervention in bladder tumors. In addition, progranulin may serve as a novel biomarker for bladder cancer.

A novel role for drebrin in regulating progranulin bioactivity in bladder cancer.

PubMed

Xu, Shi-Qiong; Buraschi, Simone; Morcavallo, Alaide; Genua, Marco; Shirao, Tomoaki; Peiper, Stephen C; Gomella, Leonard G; Birbe, Ruth; Belfiore, Antonino; Iozzo, Renato V; Morrione, Andrea

2015-05-10

We recently established a critical role for the growth factor progranulin in bladder cancer insofar as progranulin promotes urothelial cancer cell motility and contributes, as an autocrine growth factor, to the transformed phenotype by modulating invasion and anchorage-independent growth. In addition, progranulin expression is upregulated in invasive bladder cancer tissues compared to normal controls. However, the molecular mechanisms of progranulin action in bladder cancer have not been fully elucidated. In this study, we searched for novel progranulin-interacting proteins using pull-down assays with recombinant progranulin and proteomics. We discovered that drebrin, an F-actin binding protein, bound progranulin in urothelial cancer cells. We characterized drebrin function in urothelial cancer cell lines and showed that drebrin is critical for progranulin-dependent activation of the Akt and MAPK pathways and modulates motility, invasion and anchorage-independent growth. In addition, drebrin regulates tumor formation in vivo and its expression is upregulated in bladder cancer tissues compared to normal tissue controls. Our data are translationally relevant as indicate that drebrin exerts an essential functional role in the regulation of progranulin action and may constitute a novel target for therapeutic intervention in bladder tumors. In addition, drebrin may serve as novel biomarker for bladder cancer.

Suppression of progranulin expression inhibits bladder cancer growth and sensitizes cancer cells to cisplatin

PubMed Central

Stefanello, Manuela; Moskalev, Igor; Morcavallo, Alaide; Genua, Marco; Tanimoto, Ryuta; Birbe, Ruth; Peiper, Stephen C.; Gomella, Leonard G.; Belfiore, Antonino; Black, Peter C.; Iozzo, Renato V.; Morrione, Andrea

2016-01-01

We have recently demonstrated a critical role for progranulin in bladder cancer. Progranulin contributes, as an autocrine growth factor, to the transformed phenotype by modulating Akt-and MAPK-driven motility, invasion and anchorage-independent growth. Progranulin also induces F-actin remodeling by interacting with the F-actin binding protein drebrin. In addition, progranulin is overexpressed in invasive bladder cancer compared to normal tissue controls, suggesting that progranulin might play a key role in driving the transition to the invasive phenotype of urothelial cancer. However, it is not established whether targeting progranulin could have therapeutic effects on bladder cancer. In this study, we stably depleted urothelial cancer cells of endogenous progranulin by shRNA approaches and determined that progranulin depletion severely inhibited the ability of tumorigenic urothelial cancer cells to migrate, invade and grow in anchorage-independency. We further demonstrate that progranulin expression is critical for tumor growth in vivo, in both xenograft and orthotopic tumor models. Notably, progranulin levels correlated with response to cisplatin treatment and were upregulated in bladder tumors. Our data indicate that progranulin may constitute a novel target for therapeutic intervention in bladder tumors. In addition, progranulin may serve as a novel biomarker for bladder cancer. PMID:27220888

Impact of colour blindness on recognition of haematuria in bladder cancer patients.

PubMed

Katmawi-Sabbagh, Samer; Haq, Ahsanul; Jain, Sunila; Subhas, Gokul; Turnham, Helen

2009-01-01

Colour blindness might lead to failure in recognizing frank haematuria. Our aim is to investigate as to whether colour-blind males who develop bladder cancer present later with less favourable histology. Two hundred male patients with bladder cancer were assessed using Ishihara plate test for colour deficiency. Degree of haematuria, method of presentation and initial histologic findings were also determined. Colour-blind patients who develop bladder cancer present with less favourable histology compared with non-colour-blind (p = 0.01). Colour blindness was associated with presentation with more advanced bladder tumours.

Meat and components of meat and the risk of bladder cancer in the NIH-AARP Diet and Health Study

PubMed Central

Ferrucci, Leah M.; Sinha, Rashmi; Ward, Mary H.; Graubard, Barry I.; Hollenbeck, Albert R.; Kilfoy, Briseis A.; Schatzkin, Arthur; Michaud, Dominique S.; Cross, Amanda J.

2010-01-01

Background Meat could be involved in bladder carcinogenesis via multiple potentially carcinogenic meat-related compounds related to cooking and processing, including nitrate, nitrite, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons. We comprehensively investigated the association between meat and meat components and bladder cancer. Methods During 7 years of follow-up, 854 transitional cell bladder cancer cases were identified among 300,933 men and women who completed a validated food frequency questionnaire in the large prospective NIH-AARP Diet and Health Study. We estimated intake of nitrate and nitrite from processed meat and HCAs and PAHs from cooked meat using quantitative databases of measured values. We calculated total dietary nitrate and nitrite based on literature values. Results The hazard ratios (HR) and 95% confidence intervals (CI) for red meat (HR for fifth compared to first quintile=1.22, 95% CI=0.96–1.54, p-trend=0.07) and the HCA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (HR=1.19, 95% CI=0.95–1.48, p-trend=0.06) conferred a borderline statistically significant increased risk of bladder cancer. We observed positive associations in the top quintile for total dietary nitrite (HR=1.28, 95% CI=1.02–1.61, p-trend= 0.06) and nitrate plus nitrite intake from processed meat (HR=1.29 95% CI=1.00–1.67, p-trend= 0.11). Conclusions These findings provide modest support for a role for total dietary nitrite and nitrate plus nitrite from processed meat in bladder cancer. Our results also suggest a positive association between red meat and PhIP and bladder carcinogenesis. PMID:20681011

Accuracy and Readability of Websites on Kidney and Bladder Cancers.

PubMed

Azer, Samy A; Alghofaili, Maha M; Alsultan, Rana M; Alrumaih, Najla S

2017-03-09

The aim of this study was to assess the scientific accuracy and the readability level of websites on kidney and bladder cancers. The search engines Google™, Yahoo™ and Bing™ were searched independently by assessors in November 2014 using the following keywords: "bladder cancer", "kidney cancer", "patient bladder cancer", "patient kidney cancer" and "bladder and kidney cancer". Only English-language websites were selected on the bases of predetermined inclusion and exclusion criteria. Assessors independently reviewed the findings and evaluated the accuracy and quality of each website by using the DISCERN and the LIDA instruments. The readability of the websites was calculated using the Flesch-Kincaid Grade Level Index and the Coleman-Liau Readability Index. Sixty-two websites were finally included in the study. The overall accuracy scores varied; for the DISCERN, the range was 28 to 76; out of 80 (mean ± SD, 47.1 ± 12.1; median = 46.0, interquartile range (IQR) = 19.2), and for the LIDA, the range was 52 to 125; out of 144 (mean ± SD, 101.9 ± 15.2; median, 103; IQR, 16.5). The creators of these websites were universities and research centres (n = 25, 40%), foundations and associations (n = 10, 16%), commercial and pharmaceutical companies (n = 13, 21%), charities and volunteer work (n = 4, 6%) and non-university educational bodies (n = 10, 16%). The readability scores (mean ± SD) were 11.2 ± 2.2 for the Flesch-Kincaid Grade Level Index and 11.2 ± 1.6 for the Coleman-Liau Readability Index. The accuracy and the quality of the websites on kidney and bladder cancers varied. In most websites, there were deficiencies in clarity of aims, presenting symptoms, investigations and treatment options. The readability matched grades 10-11 literacy levels-a level above the public readability level. The study highlights the needs for further improvement of the online information created for public and patients with kidney and bladder cancers.

Research progress on bladder cancer molecular genetics.

PubMed

Kang, Zhengjun; Li, Yuhui; Yu, Yang; Guo, Zhan

2014-11-01

Bladder cancer is a common malignant urinary tumor with a high rate of recurrence and quick progression, which threats human health. With the research on bladder cancer molecular genetics, the knowledge of gene modification and the development of molecular detection methods, more tumor markers have been discovered, which may have potential for early diagnosis, clinical examination and prognosis. This article reviews the research progress on bladder cancer molecular genetics.

Systematic Review of Studies Reporting Positive Surgical Margins After Bladder Neck Sparing Radical Prostatectomy.

PubMed

Bellangino, Mariangela; Verrill, Clare; Leslie, Tom; Bell, Richard W; Hamdy, Freddie C; Lamb, Alastair D

2017-11-07

Bladder neck preservation (BNP) during radical prostatectomy (RP) has been proposed as a method to improve early recovery of urinary continence after radical prostatectomy. However, there is concern over a possible increase in the risk of positive surgical margins and prostate cancer recurrence rate. A recent systematic review and meta-analysis reported improved early recovery and overall long-term urinary continence without compromising oncologic control. The aim of our study was to perform a critical review of the literature to assess the impact on bladder neck and base margins after bladder neck sparing radical prostatectomy. We carried out a systematic review of the literature using Pubmed, Scopus and Cochrane library databases in May 2017 using medical subject headings and free-text protocol according to PRISMA guidelines. We used the following search terms: bladder neck preservation, prostate cancer, radical prostatectomy and surgical margins. Studies focusing on positive surgical margins (PSM) in bladder neck sparing RP pertinent to the objective of this review were included. Overall, we found 15 relevant studies reporting overall and site-specific positive surgical margins rate after bladder neck sparing radical prostatectomy. This included two RCTs, seven prospective comparative studies, two retrospective comparative studies and four case series. All studies were published between 1993 and 2015 with sample sizes ranging between 50 and 1067. Surgical approaches included open, laparoscopic and robot-assisted radical prostatectomy. The overall and base-specific PSM rates ranged between 7-36% and 0-16.3%, respectively. Mean base PSM was 4.9% in those patients where bladder neck sparing was performed, but only 1.85% in those without sparing. Bladder neck preservation during radical prostatectomy may increase base-positive margins. Further studies are needed to better investigate the impact of this technique on oncological outcomes. A future paradigm could include modification of intended approach to bladder neck dissection when anterior base lesions are identified on pre-operative MRI.

Egg consumption and risk of bladder cancer: a meta-analysis.

PubMed

Li, Fei; Zhou, You; Hu, Rui-ting; Hou, Li-na; Du, Yue-Jun; Zhang, Xin-ji; Olkkonen, Vesa M; Tan, Wan-long

2013-01-01

The findings of epidemiologic studies on the association between egg consumption and bladder cancer risk remain conflicting. We conducted a meta-analysis to clarify the potential association between egg consumption and bladder cancer risk. Four cohort studies and 9 case-control studies in the PubMed database through February 2012 were identified on egg consumption and risk of bladder cancer involving 2715 cases and 184,727 participants. Random-effects models were used to calculate the summary relative risk estimates (SRRE) based on the highest compared with the lowest category of egg consumption. In addition, we performed stratified analyses and sensitivity and dose-response analyses to examine the association. Overall, no significant association was observed between egg consumption and bladder cancer (SRRE = 1.11 95% CI: 0.90-1.35). However, increased risk of bladder cancer was detected in North/South America (SRRE = 1.40 95% CI: 1.05-1.86) and, moreover, fried egg intake positively associated with bladder cancer as well (SRRE = 2.04, 95% CI: 1.41-2.95). In conclusion, our findings suggest no significant association between egg consumption and bladder cancer risk, except for a possible positive relationship with the intake of fried eggs based on the limited number of studies. Additional studies, especially large prospective cohort studies, are warranted to confirm these findings.

Photodynamic diagnosis of bladder cancer in ex vivo urine cytology

NASA Astrophysics Data System (ADS)

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.

Shared occupational risks for transitional cell cancer of the bladder and renal pelvis among men and women in Sweden.

PubMed

Wilson, Robin Taylor; Donahue, Mark; Gridley, Gloria; Adami, Johanna; El Ghormli, Laure; Dosemeci, Mustafa

2008-02-01

Unlike cancer of the bladder, cancer of the renal pelvis is not considered an occupational cancer and little is known about risks among women. Using the Swedish national census and cancer registry-linked data (1971-1989), we identified transitional cell cancers of the renal pelvis (N = 1,374) and bladder (N = 21,591). Correlation between cancer sites for the standardized incidence ratios (SIR) were determined using Pearson's coefficient of the log SIR. Relative risks of job exposure matrix variables were calculated using Poisson regression. Both cancer sites were significantly elevated among women and men employed in the machine/electronics industry, sedentary work, and indoor work, and men in the metal industry. The highest proportion of the bladder (12%) and renal pelvis (14%) cancers occurred among men employed in shop and construction metal work. Risks by industry were more correlated among women (r = 0.49, P = 0.002) than men (r = 0.24, P = 0.04). Cancers of the renal pelvis were elevated in several occupational and industry groups for which there was no elevated bladder cancer risk. Cancers of the renal pelvis and bladder share common occupational risk factors that may be more frequent among women. In addition, there may be some jobs that pose an increased risk specifically for cancer of the renal pelvis but not bladder.

The evolution of bladder cancer genomics: What have we learned and how can we use it?

PubMed

Audenet, François; Attalla, Kyrollis; Sfakianos, John P

2018-03-21

With advancements in molecular biology techniques, great progress has been made in the understanding of urothelial carcinoma pathogenesis. To examine the historic description of molecular alterations in bladder cancer and their evolution towards our current comprehension of the biology of the disease. Historically, a two-pathway model was described from histological and cytogenetic studies: low-grade papillary non-muscle invasive bladder cancers (NMIBC) were described to arise from epithelial hyperplasia with loss of chromosome 9 as an early event, whereas muscle-invasive bladder cancers (MIBC) were considered to develop from dysplasia, associated with genetic instability. Although there could be connections between the 2 pathways, NMIBC and MIBC were largely believed to develop secondary to different molecular alterations. Next-generation sequencing has allowed important insights into cancer biology and a better understanding of the pathways involved in bladder cancer pathogenesis and heterogeneity. Urothelial carcinoma has been found to have a high frequency of somatic mutations compared to other solid tumors, including several mutations in multiple signaling pathways, such as cell cycle regulators (TP53, RB1), RTK/RAS/RAF pathway, PI3K/AKT/mTOR pathway and TERT gene promoter. Epigenetic changes and mutations in chromatin remodeling genes are especially frequent in bladder cancer. Mutations in FGFR3 and KDM6A are more common in NMIBC than in MIBC, whereas mutations in TP53 and KMT2D are more common in MIBC, suggesting the previously hypothesized 2 different pathways, with a subset of tumors progressing from NMIBC to MIBC. Using comprehensive RNA expression profiling studies, at least 5 subtypes of bladder cancer have been identified, the most fundamental division being Basal/Squamous-like and Luminal. These subtypes have different prognoses, natural histories and responses to systemic treatments: Luminal subtypes are enriched with papillary histology and have a better prognosis, while Basal/Squamous-like subtypes are enriched with squamous features, are associated with advanced stage at presentation, and portend a worse prognosis. This new understanding of bladder cancer will optimistically translate into better understanding of this heterogeneous disease and lead to improvement in patient outcome and quality of life through better tailored treatments. Copyright © 2018 Elsevier Inc. All rights reserved.

Bladder cancer incidence and exposure to polycyclic aromatic hydrocarbons among asphalt pavers.

PubMed

Burstyn, Igor; Kromhout, Hans; Johansen, Christoffer; Langard, Sverre; Kauppinen, Timo; Shaham, Judith; Ferro, Gilles; Boffetta, Paolo

2007-08-01

To investigate the association between exposures to polycyclic aromatic hydrocarbons (PAH) that arises during asphalt paving, and risk of bladder cancer. 7298 men included in the historical cohort were first employed between 1913 and 1999 in companies applying asphalt in Denmark, Norway, Finland and Israel. The minimal duration of employment for inclusion in the cohort was two seasons of work. Occupational histories were extracted from personnel files. A follow-up for cancer incidence was conducted through national cancer registries. The authors estimated exposures to benzo(a)pyrene as a marker for 4-6 ring PAH. Exposures were reconstructed by using information about changes in asphalt paving technology in each company over time, the modelled relation between production characteristics and exposure levels, and job histories. Relative risks and associated 95% confidence intervals were estimated using Poisson regression. 48 bladder cancers among asphalt paving workers were detected; of these, 39 cases were exposed at least 15 years before the diagnosis. Cumulative exposure to PAH was not associated with the incidence of bladder cancer. The association with average exposure became stronger when 15-year lag was considered, revealing a twofold increase in relative bladder cancer risk in the two higher exposure categories. There was an indication of exposure-response association with lagged averaged exposure. Risk estimates were adjusted for age, country, duration of employment and calendar period, did not show heterogeneity among countries and did not materially change when re-estimated after excluding non-primary cancers from follow-up. Previously conducted sensitivity analysis indicates that confounding by cigarette smoking is an unlikely explanation for the observed exposure-response trends. The authors were unable to control for all possible sources of confounding and bias. The results do not allow conclusion on the presence or absence of a causal link between exposures to PAH and risk of bladder cancer among asphalt workers.

Bladder cancer incidence and exposure to polycyclic aromatic hydrocarbons among asphalt pavers

PubMed Central

Burstyn, Igor; Kromhout, Hans; Johansen, Christoffer; Langard, Sverre; Kauppinen, Timo; Shaham, Judith; Ferro, Gilles; Boffetta, Paolo

2007-01-01

Objectives To investigate the association between exposures to polycyclic aromatic hydrocarbons (PAH) that arises during asphalt paving, and risk of bladder cancer. Methods 7298 men included in the historical cohort were first employed between 1913 and 1999 in companies applying asphalt in Denmark, Norway, Finland and Israel. The minimal duration of employment for inclusion in the cohort was two seasons of work. Occupational histories were extracted from personnel files. A follow‐up for cancer incidence was conducted through national cancer registries. The authors estimated exposures to benzo(a)pyrene as a marker for 4–6 ring PAH. Exposures were reconstructed by using information about changes in asphalt paving technology in each company over time, the modelled relation between production characteristics and exposure levels, and job histories. Relative risks and associated 95% confidence intervals were estimated using Poisson regression. Results 48 bladder cancers among asphalt paving workers were detected; of these, 39 cases were exposed at least 15 years before the diagnosis. Cumulative exposure to PAH was not associated with the incidence of bladder cancer. The association with average exposure became stronger when 15‐year lag was considered, revealing a twofold increase in relative bladder cancer risk in the two higher exposure categories. There was an indication of exposure‐response association with lagged averaged exposure. Risk estimates were adjusted for age, country, duration of employment and calendar period, did not show heterogeneity among countries and did not materially change when re‐estimated after excluding non‐primary cancers from follow‐up. Previously conducted sensitivity analysis indicates that confounding by cigarette smoking is an unlikely explanation for the observed exposure‐response trends. Conclusions The authors were unable to control for all possible sources of confounding and bias. The results do not allow conclusion on the presence or absence of a causal link between exposures to PAH and risk of bladder cancer among asphalt workers. PMID:17332134

The Epigenetics of Kidney Cancer and Bladder Cancer

PubMed Central

Hoffman, Amanda M.; Cairns, Paul

2012-01-01

Summary This review focuses on the epigenetic alterations of aberrant promoter hypermethylation of genes, histone modifications or RNA interference in cancer cells. The current knowledge of hypermethylation of allele(s) in classical tumor suppressor genes in inherited and sporadic cancer, candidate tumor suppressor and other cancer genes is summarized gene by gene. Global and array-based studies of tumor cell hypermethylation are discussed. The importance of standardization of scoring of the methylation status of a gene is highlighted. The histone marks associated with hypermethylated genes, and the microRNAs with dysregulated expression, in kidney or bladder tumor cells are also discussed. Kidney cancer has the highest mortality rate of the genitourinary cancers. There are management issues with the high recurrence rate of superficial bladder cancer while muscle invasive bladder cancer has a poor prognosis. These clinical problems are the basis for translational application of gene hypermethylation to the diagnosis and prognosis of kidney and bladder cancer. PMID:22126150

Screening for Bladder and Other Urothelial Cancers

MedlinePlus

... decrease the risk of dying from cancer. Scientists study screening tests to find those with the fewest risks and ... recovery . There is no standard or routine screening test for bladder cancer. Screening for bladder cancer is under study and there are screening clinical trials taking place ...

Protoporphyrin IX induced by 5-aminolevulinic acid in bladder cancer cells in voided urine can be extracorporeally quantified using a spectrophotometer.

PubMed

Nakai, Yasushi; Anai, Satoshi; Onishi, Sayuri; Masaomi, Kuwada; Tatsumi, Yoshihiro; Miyake, Makito; Chihara, Yoshitomo; Tanaka, Nobumichi; Hirao, Yoshihiko; Fujimoto, Kiyohide

2015-06-01

We evaluated the feasibility of photodynamic diagnosis of bladder cancer by spectrophotometric analysis of voided urine samples after extracorporeal treatment with 5-aminolevulinic acid (ALA). Sixty-one patients with bladder cancer, confirmed histologically after the transurethral resection of a bladder tumor, were recruited as the bladder cancer group, and 50 outpatients without history of urothelial carcinoma or cancer-related findings were recruited as the control group. Half of the voided urine sample was incubated with ALA (ALA-treated sample), and the rest was incubated without treatment (ALA-untreated sample). For detecting cellular protoporphyrin IX levels, intensity of the samples at the excitation wavelength of 405 nm was measured using a spectrophotometer. The difference between the intensity of the ALA-treated and ALA-untreated samples at 635 nm was calculated. The differences in the bladder cancer group were significantly greater than those in the control group (p < 0.001). These differences were also significantly greater in patients with high-grade tumors than in those with low-grade tumors (p = 0.004), and also in patients with invasive bladder cancer than in those with noninvasive bladder cancer (p = 0.007). The area under the curve was 0.84. Sensitivity and specificity of the method were 82% and 80%, respectively. We demonstrated that protoporphyrin IX levels in urinary cells treated with ALA could be quantitatively detected by spectrophotometer in patients with bladder cancer. Therefore, this cancer detection system has a potential for clinical use. Copyright © 2015 Elsevier B.V. All rights reserved.

NMP22 BladderChek Test: point-of-care technology with life- and money-saving potential.

PubMed

Tomera, Kevin M

2004-11-01

A new, relatively obscure tumor marker assay, the NMP22 BladderChek Test (Matritech, Inc.), represents a paradigm shift in the diagnosis and management of urinary bladder cancer (transitional cell carcinoma). Specifically, BladderChek should be employed every time a cystoscopy is performed, with corresponding changes in the diagnostic protocol and the guidelines of the American Urological Association for the diagnosis and management of bladder cancer. Currently, cystoscopy is the reference standard and NMP22 BladderChek Test in combination with cystoscopy improves the performance of cystoscopy. At every stage of disease, BladderChek provides a higher sensitivity for the detection of bladder cancer than cytology, which now represents the adjunctive standard of care. Moreover, BladderChek is four-times more sensitive than cytology and is available at half the cost. Early detection of bladder cancer improves prognosis, quality of life and survival. BladderChek may be analogous to the prostate-specific antigen test and eventually expand beyond the urologic setting into the primary care setting for the testing of high-risk patients characterized by smoking history, occupational exposures or age.

Economic Burden of Bladder Cancer Across the European Union.

PubMed

Leal, Jose; Luengo-Fernandez, Ramon; Sullivan, Richard; Witjes, J Alfred

2016-03-01

More than 120,000 people are diagnosed annually with bladder cancer in the 28 countries of the European Union (EU). With >40,000 people dying of it each year, it is the sixth leading cause of cancer. However, to date, no systematic cost-of-illness study has assessed the economic impact of bladder cancer in the EU. To estimate the annual economic costs of bladder cancer in the EU for 2012. Country-specific cancer cost data were estimated using aggregate data on morbidity, mortality, and health care resource use, obtained from numerous international and national sources. Health care costs were estimated from expenditures on primary, outpatient, emergency, and inpatient care, as well as medications. Costs of unpaid care and lost earnings due to morbidity and early death were estimated. Bladder cancer cost the EU €4.9 billion in 2012, with health care accounting for €2.9 billion (59%) and representing 5% of total health care cancer costs. Bladder cancer accounted for 3% of all cancer costs in the EU (€143 billion) in 2012 and represented an annual health care cost of €57 per 10 EU citizens, with costs varying >10 times between the country with the lowest cost, Bulgaria (€8 for every 10 citizens), and highest cost, Luxembourg (€93). Productivity losses and informal care represented 23% and 18% of bladder cancer costs, respectively. The quality and availability of comparable cancer-related data across the EU need further improvement. Our results add to essential public health and policy intelligence for delivering affordable bladder cancer care systems and prioritising the allocation of public research funds. We looked at the economic costs of bladder cancer across the European Union (EU). We found bladder cancer to cost €4.9 billion in 2012, with health care accounting for €2.9 billion. Our study provides data that can be used to inform affordable cancer care in the EU. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

A Methylation Panel for Bladder Cancer — EDRN Public Portal

Cancer.gov

Participate in a prevalidation study for methylation based detection of bladder cancer. In addition, a panel of three markers identified will be evaluated for their ability to a) identify bladder cancer patients from those with benign urologic disease; b) identify patients with superficial (papillary) cancers from those with high grade invasive cancers

Expression of ferrochelatase has a strong correlation in protoporphyrin IX accumulation with photodynamic detection of bladder cancer.

PubMed

Nakai, Yasushi; Tatsumi, Yoshihiro; Miyake, Makito; Anai, Satoshi; Kuwada, Masaomi; Onishi, Sayuri; Chihara, Yoshitomo; Tanaka, Nobumichi; Hirao, Yoshihiko; Fujimoto, Kiyohide

2016-03-01

The mechanism underlying the increased levels of protoporphyrin IX in bladder cancer remains unclear. Here, we focus on proteins associated with protoporphyrin IX accumulation in bladder cancer cells and investigate the protein that plays a key role in increased protoporphyrin IX accumulation in bladder cancer cells. Western blotting was used to determine the expression of peptide transporter 1, hydroxymethylbilane synthase, ferrochelatase, ATP-binding cassette 2, and heme oxygenase-1 in bladder cancer cell line cells. We evaluated the correlation between the expression of each protein and accumulated protoporphyrin IX in these cells using Pearson's correlation analysis. Immunohistochemistry was used to estimate the expression of the same five proteins in samples from 75 patients who underwent transurethral resection of bladder tumors. The correlation between the expression of each protein in cells from resected bladder specimens and accumulated protoporphyrin IX in bladder cancer cells in voided urine was evaluated using Pearson's correlation analysis. The expression of ferrochelatase showed a significant negative correlation with protoporphyrin IX accumulation in vitro (p=0.04). The expression of peptide transporter 1 (p<0.01, R=0.39), heme oxygenase-1 (p<0.01, R=0.33), and ferrochelatase (p<0.01, R=0.75) in resected bladder specimens by immunohistochemistry was correlated with protoporphyrin IX accumulation in bladder cancer cells in voided urine. On multivariate analysis, the expression of ferrochelatase (p=0.03) was significant factors to predict positive 5-aminolevulinic acid-induced fluorescent cytology. The expression of ferrochelatase has a strong correlation in protoporphyrin IX accumulation with photodynamic detection of bladder cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

Screening biomarkers of bladder cancer using combined miRNA and mRNA microarray analysis.

PubMed

Jin, Ning; Jin, Xuefei; Gu, Xinquan; Na, Wanli; Zhang, Muchun; Zhao, Rui

2015-08-01

Biomarkers, such as microRNAs (miRNAs) may be useful for the diagnosis of bladder cancer. In order to understand the molecular mechanisms underlying bladder cancer, differentially expressed miRNAs (DE-miRNAs) and their target genes in bladder cancer were analyzed. In the present study, miRNA and mRNA expression profiles (GSE40355) were obtained from the Gene Expression Omnibus. These consisted of healthy bladder samples (n=8) and urothelial carcinoma samples (low-grade, n=8 and high-grade, n=8). DE-miRNAs and differentially expressed genes (DEGs) were identified using the limma package and the Benjamin and Hochberg method from the multtest package in R. Target genes of DE-miRNAs were screened. Associations between DEGs were investigated using STRING, and an interaction network was constructed using Cytoscape. Functional and pathway enrichment analyses were performed for DEGs from the interaction network. 87 DE-miRNAs and 2058 DEGs were screened from low-grade bladder cancer samples, and 40 DE-miRNAs and 2477 DEGs were screened from high-grade bladder cancer samples. DE-target genes were significantly associated with the regulation of cell apoptosis. Bladder cancer, non-small cell lung cancer and pancreatic cancer biological pathways were found to be enriched. The results of the present study demonstrated that E2F transcription factor 1, which is targeted by miR-106b, and cyclin-dependent kinase inhibitor 2A (CDKN2A) and V-Erb-B2 avian erythroblastic leukemia viral oncogene homolog-2, which are targeted by miR-125b, participate in the bladder cancer pathway. In conclusion, DE-miRNAs in bladder cancer tissue samples and DE-targeted genes, such as miR-106b and CDKN2A, which were identified in the present study, may provide the basis for targeted therapy for breast cancer and enhance understanding of its pathogenesis.

The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR).

PubMed

Xiong, Yaoyao; Wang, Long; Li, Yuan; Chen, Minfeng; He, Wei; Qi, Lin

2017-01-01

Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in the progression of several tumors. The interaction between lncRNA and miRNA or miRNA's target genes is reported to play crucial roles in malignancy. In addition, Androgen receptor (AR) is considered to be involved in bladder cancer progression. In this study, we investigated the role of XIST in human bladder cancer and its interaction with miR-124 and AR. XIST and AR expression was detected in bladder tumor samples and cell lines. Effects of XIST and AR on bladder cancer cells growth, invasion and migration were analyzed. Bioinformatic analysis and luciferase assays were used to identify the interaction among XIST, AR and miR-124. The correlations of miR-124 with XIST and AR in bladder cancer samples were statistically analyzed. XIST and AR were upregulated in bladder cancer tissues and positively correlated. Higher XIST and AR expression were related to poorer TNM stage of bladder cancer. XIST knockdown reduced bladder cancer cells' proliferation, invasion and migration. While this inhibitory effect could be partially restored by AR overexpression. XIST inhibited miR-124 expression by directly targeting. Moreover, miR-124 could bind to the 3'UTR of AR to regulate its expression. MiR-124 inhibition partially restored the XIST knockdown-induced reduction of AR, c-myc, p27, MMP13 and MMP9 expression. In bladder cancer tissues, miR-124 level was inversely correlated with the expression of XIST and AR, respectively. These findings indicated that XIST might be an oncogenic lncRNA that promoted the bladder cancer growth, invasion and migration via miR-124 dependent AR regulation. © 2017 The Author(s). Published by S. Karger AG, Basel.

Histone deacetylases (HDACs) in XPC gene silencing and bladder cancer

PubMed Central

2011-01-01

Bladder cancer is one of the most common malignancies and causes hundreds of thousands of deaths worldwide each year. Bladder cancer is strongly associated with exposure to environmental carcinogens. It is believed that DNA damage generated by environmental carcinogens and their metabolites causes development of bladder cancer. Nucleotide excision repair (NER) is the major DNA repair pathway for repairing bulk DNA damage generated by most environmental carcinogens, and XPC is a DNA damage recognition protein required for initiation of the NER process. Recent studies demonstrate reduced levels of XPC protein in tumors for a majority of bladder cancer patients. In this work we investigated the role of histone deacetylases (HDACs) in XPC gene silencing and bladder cancer development. The results of our HDAC inhibition study revealed that the treatment of HTB4 and HTB9 bladder cancer cells with the HDAC inhibitor valproic acid (VPA) caused an increase in transcription of the XPC gene in these cells. The results of our chromatin immunoprecipitation (ChIP) studies indicated that the VPA treatment caused increased binding of both CREB1 and Sp1 transcription factors at the promoter region of the XPC gene for both HTB4 and HTB9 cells. The results of our immunohistochemistry (IHC) staining studies further revealed a strong correlation between the over-expression of HDAC4 and increased bladder cancer occurrence (p < 0.001) as well as a marginal significance of increasing incidence of HDAC4 positivity seen with an increase in severity of bladder cancer (p = 0.08). In addition, the results of our caspase 3 activation studies demonstrated that prior treatment with VPA increased the anticancer drug cisplatin-induced activation of caspase 3 in both HTB4 and HTB9 cells. All of these results suggest that the HDACs negatively regulate transcription of the XPC gene in bladder cancer cells and contribute to the severity of bladder tumors. PMID:21507255

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Kuiqing; Chen, Xu; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120

Pirarubicin is widely used in intravesical chemotherapy for bladder cancer, but its efficacy is limited due to drug resistance; the mechanism has not been well studied. Emerging evidence shows that autophagy can be a novel target for cancer therapy. This study aimed to investigate the role of autophagy in pirarubicin-treated bladder cancer cells. Bladder cancer cells EJ and J82 were treated with pirarubicin, siRNA, 3-methyladenine or hydroxychloroquine. Cell proliferation and apoptosis were tested by cell survival assay and flow cytometric analysis, respectively. Autophagy was evaluated by immunoblotting before and after the treatments. The phosphorylated mammalian target of rapamycin, serine/threonine kinasemore » p70 S6 kinase, and eukaryotic translation initiation factor 4E binding protein 1 were also investigated by immunoblotting. We found that pirarubicin could induce autophagy in bladder cancer cells. Inhibition of autophagy by 3-methyladenine, hydroxychloroquine or knockdown of autophagy related gene 3 significantly increased apoptosis in pirarubicin-treated bladder cancer cells. Pirarubicin-induced autophagy was mediated via the mTOR/p70S6K/4E-BP1 signaling pathway. In conclusion, autophagy induced by pirarubicin plays a cytoprotective role in bladder cancer cells, suggesting that inhibition of autophagy may improve efficacy over traditional pirarubicin chemotherapy in bladder cancer patients. - Highlights: • Pirarubicin induced autophagy in bladder cancer cells. • Inhibition of autophagy enhanced pirarubicin-induced apoptosis. • Pirarubicin induced autophagy through inhibition of mTOR signaling pathway.« less

Expression of ERβ and its co-regulators p300 and NCoR in human transitional cell bladder cancer.

PubMed

Kontos, Stylianos; Papatsoris, Athanasios; Kominea, Athina; Melachrinou, Maria; Tanoglidi, Anna; Kachrilas, Stefanos; Karavitakis, Markos; Balampani, Eleni; Sotiropoulou-Bonikou, Georgia

2011-01-01

Several data support a possible role of estrogens in bladder carcinogenesis, mediated mainly through estrogen receptor-β (ERβ). We study the expression of ERβ and its co-regulators p300 and nuclear co-repressor (NCoR) in patients with bladder cancer. One hundred and eleven consecutive patients (74 males and 37 females), aged 23-90 years (mean 70 ± 10) diagnosed with transitional cell bladder cancer were included in this study. The control group consisted of 29 patients that underwent transurethral prostatectomy and consented to simultaneous bladder biopsies. Immunohistochemical studies took place on formalin-fixed, paraffin-embedded sections from the TUR (transurethral resection) specimens. We studied the expression of ERβ, p300 and NCoR.χ(2) test was used to evaluate the relationship between the histological grade and ERβ expression, grade and co-regulators expression and grade and gender. Spearman rank correlation coefficient (r) was used in order to estimate the direction and strength of correlations between histological grade and ERβ-p300-NCoR expressions. The Cochran-Armitage test for trend was applied in order to examine possible trends across the ordered levels of histological grade. ERβ was more frequently expressed in the nucleus of normal bladder epithelium compared to malignant bladder epithelium with statistical significant association (r = -0.25, p = 0.003). The p300 was expressed only in the nucleus of bladder cancer cells and a positive correlation between molecular expression and cancer progression was demonstrated (r = 0.55, p < 0.001). NCoR immunostaining was demonstrated in the nuclei of bladder cells. Nuclear staining was significantly higher in normal tissue than in cancer cells (r = -0.33, p < 0.001), with negative correlation. Furthermore, its expression in grade I tumors was significantly higher than in grade II (r = -0.46, p < 0.001) and grade III tumors (r = -0.51, p < 0.001). Thus, like ERβ, NCoR expression in bladder epithelium decreased during cancer progression and loss of cell differentiation. There was no correlation between the levels of expression of the three proteins in normal bladder epithelium, but there was an inverse correlation between the nuclear expression of ERβ and p300 in carcinomas (r = -3.88, p = 0.042). Statistical significant association was established when correlating ERβ expression with NCoR expression (r = 0.273, p = 0.005), while co-regulators' nuclear expression did not correlate with each other (p > 0.05). In bladder carcinogenesis, we demonstrated inhibition in the expression of ERβ and its co-repressor NCoR as well as increased expression of the co-activator p300. Copyright © 2011 S. Karger AG, Basel.

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

PubMed

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.

Updated results of bladder-sparing trimodality approach for invasive bladder cancer.

PubMed

Zapatero, Almudena; Martin de Vidales, Carmen; Arellano, Ramón; Bocardo, Gloria; Pérez, Mar; Ríos, Patricia

2010-01-01

To update long-term results with selective organ preservation in invasive bladder cancer using aggressive transurethral resection of bladder tumor (TURBT) and radiochemotherapy (RCT) and to identify treatment factors that may predict overall survival (OS). Between 1990 and 2007, a total of 74 patients with T2-T4 bladder cancer were enrolled in 2 sequential bladder-sparing protocols including aggressive TURB and RCT. From 1990 to 1999, 41 patients were included in protocol no. 1 (P1) that consisted of three cycles of neoadjuvant methotrexate, cisplatin, and vinblastine (MCV) chemotherapy prior to re-evaluation and followed by radiotherapy (RT) 60 Gy in complete responders. Between 2000 and 2007, 33 patients were entered in protocol no. 2 (P2) that consisted of concurrent RCT 64, 8 Gy with weekly cisplatin. In case of invasive residual tumor or recurrence, salvage cystectomy was recommended. Primary endpoints were OS, overall survival with bladder preservation (OSB), and late toxicity. The mean follow-up for the whole series was 54 months (range 9-156), 69 months for patients in P1 and 36 months for patients in P2. The actuarial 5-year OS and OSB for all series were 72% and 60%, respectively. Distant metastases were diagnosed in 11 (15%) patients. Grade 3 late genitourinary (GU) and intestinal (GI) complications were 5% and 1.3%, respectively. There were no significant differences in the incidence of superficial recurrences (P = 0.080), muscle-invasive relapses (P = 0.722), distant metastasis (P = 0.744), grade >/=2 late complications (P = 0.217 for GU and P = 0.400 for GI), and death among the 2 protocols (P value for OS = 0.643; P value for OSB = 0.532). These data confirm that trimodality therapy with bladder preservation represents a real alternative to radical cystectomy in selected patients, resulting in an acceptable rate of the long-term survivors retaining functional bladders. Copyright 2010 Elsevier Inc. All rights reserved.

Lifetime exposure to arsenic in drinking water and bladder cancer: a population-based case–control study in Michigan, USA

PubMed Central

Slotnick, Melissa J.; AvRuskin, Gillian A.; Schottenfeld, David; Jacquez, Geoffrey M.; Wilson, Mark L.; Goovaerts, Pierre; Franzblau, Alfred; Nriagu, Jerome O.

2014-01-01

Objective Arsenic in drinking water has been linked with the risk of urinary bladder cancer, but the dose–response relationships for arsenic exposures below 100 µg/L remain equivocal. We conducted a population-based case–control study in southeastern Michigan, USA, where approximately 230,000 people were exposed to arsenic concentrations between 10 and 100 µg/L. Methods This study included 411 bladder cancer cases diagnosed between 2000 and 2004, and 566 controls recruited during the same period. Individual lifetime exposure profiles were reconstructed, and residential water source histories, water consumption practices, and water arsenic measurements or modeled estimates were determined at all residences. Arsenic exposure was estimated for 99% of participants’ person-years. Results Overall, an increase in bladder cancer risk was not found for time-weighted average lifetime arsenic exposure >10 µg/L when compared with a reference group exposed to <1 µg/L (odds ratio (OR) = 1.10; 95% confidence interval (CI): 0.65, 1.86). Among ever-smokers, risks from arsenic exposure >10 µg/L were similarly not elevated when compared to the reference group (OR = 0.94; 95% CI: 0.50, 1.78). Conclusions We did not find persuasive evidence of an association between low-level arsenic exposure and bladder cancer. Selecting the appropriate exposure metric needs to be thoughtfully considered when investigating risk from low-level arsenic exposure. PMID:20084543

New genetic variants of LATS1 detected in urinary bladder and colon cancer.

PubMed

Saadeldin, Mona K; Shawer, Heba; Mostafa, Ahmed; Kassem, Neemat M; Amleh, Asma; Siam, Rania

2014-01-01

LATS1, the large tumor suppressor 1 gene, encodes for a serine/threonine kinase protein and is implicated in cell cycle progression. LATS1 is down-regulated in various human cancers, such as breast cancer, and astrocytoma. Point mutations in LATS1 were reported in human sarcomas. Additionally, loss of heterozygosity of LATS1 chromosomal region predisposes to breast, ovarian, and cervical tumors. In the current study, we investigated LATS1 genetic variations including single nucleotide polymorphisms (SNPs), in 28 Egyptian patients with either urinary bladder or colon cancers. The LATS1 gene was amplified and sequenced and the expression of LATS1 at the RNA level was assessed in 12 urinary bladder cancer samples. We report, the identification of a total of 29 variants including previously identified SNPs within LATS1 coding and non-coding sequences. A total of 18 variants were novel. Majority of the novel variants, 13, were mapped to intronic sequences and un-translated regions of the gene. Four of the five novel variants located in the coding region of the gene, represented missense mutations within the serine/threonine kinase catalytic domain. Interestingly, LATS1 RNA steady state levels was lost in urinary bladder cancerous tissue harboring four specific SNPs (16045 + 41736 + 34614 + 56177) positioned in the 5'UTR, intron 6, and two silent mutations within exon 4 and exon 8, respectively. This study identifies novel single-base-sequence alterations in the LATS1 gene. These newly identified variants could potentially be used as novel diagnostic or prognostic tools in cancer.

[Bladder-conserving treatment for bladder cancer: potential of and developments in radiotherapy].

PubMed

Hulshof, Maarten C C M; Pieters, Bradley R; Koning, Caro C E

2013-01-01

The standard treatment for muscle-invasive bladder cancer is surgical removal of the bladder and construction of a neobladder. Recently, important improvements have been made in the potential for bladder-conserving treatment using radiotherapy. External beam radiotherapy has undergone technological improvements, as a result of which it is possible to radiate the tumour more precisely while decreasing radiation to healthy tissue. Radiochemotherapy improves local recurrence-free and overall survival compared with radiotherapy alone. The results of this combined treatment are comparable with those of surgery. Additionally, Dutch radiotherapy departments have collected data in a national database of 1040 selected patients with confined bladder cancer. These patients were treated with external beam radiation, limited surgery and brachytherapy. The 5-year local recurrence-free survival was 75%. Bladder conserving treatment options for muscle-invasive bladder cancer should be discussed during the multidisciplinary meeting.

Clinical and pathological implications of miRNA in bladder cancer

PubMed Central

Braicu, Cornelia; Cojocneanu-Petric, Roxana; Chira, Sergiu; Truta, Anamaria; Floares, Alexandru; Petrut, Bogdan; Achimas-Cadariu, Patriciu; Berindan-Neagoe, Ioana

2015-01-01

MicroRNAs (miRNAs) are small, noncoding RNA species with a length of 20–22 nucleotides that are recognized as essential regulators of relevant molecular mechanisms, including carcinogenesis. Current investigations show that miRNAs are detectable not only in different tissue types but also in a wide range of biological fluids, either free or trapped in circulating microvesicles. miRNAs were proven to be involved in cell communication, both in pathological and physiological processes. Evaluation of the global expression patterns of miRNAs provides key opportunities with 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. PMID:25653521

Robotic-assisted versus open radical cystectomy in bladder cancer: A meta-analysis of four randomized controlled trails.

PubMed

Tang, Jin-Qiu; Zhao, Zhihong; Liang, Yiwen; Liao, Guixiang

2018-02-01

Robot-assisted radical cystectomy (RARC) is increasing annually for treatment of bladder cancer. The objective of this meta-analysis was to compare the safety and efficacy of RARC and open radical cystectomy (ORC) for bladder cancer. Our meta-analysis searches were conducted using PubMed, Web of Science, and Cochrane Library databases to identify randomized controlled trials (RCT) assessing the two techniques. Four RCT studies were identified, including 239 cases. Our studies indicated that RARC was associated with longer operative time (WMD: 69.69, 95% CI:17.25 to122.12; P= 0.009), lower estimated blood loss (WMD: -299.83, 95% CI:-414.66to -184.99; P<0.00001). The two groups had no significant difference in overall perioperative complications, length of hospital stay, lymph node yield and positive surgical margins. RARC is mini-invasive alternative to ORC for bladder cancer. The advantage of RARC was reduced estimated blood loss. More studies are needed to compare the two techniques. Copyright © 2017 John Wiley & Sons, Ltd.

Bladder cancer and occupational exposure to leather.

PubMed Central

Marrett, L D; Hartge, P; Meigs, J W

1986-01-01

A large case-control study of bladder cancer (2982 cases; 5782 controls) included information about occupational exposure to leather. Occupational histories of exposed white study subjects were reviewed and 150 were determined to have had "true" on the job exposure to leather. The odds ratio estimate (OR) of bladder cancer associated with such exposure in white subjects (n = 8063) was 1.4 (95% confidence limits = 1.0, 1.9) after adjustment for sex, age, and cigarette smoking. The risk was highest in those first employed in a leather job before 1945, although no dose-response relation with duration of leather employment was found. Subjects employed in "dusty" leather jobs had a slightly higher risk than those with other types of leather jobs. Our results are consistent with reports of an increased risk of bladder cancer associated with exposure to leather. Although the agents responsible have not been identified, our findings of an increased risk associated with exposure in the earlier years of this century and in dusty jobs suggest that leather dusts may be important. PMID:3947575

Urinary retinoic acid receptor-β2 gene promoter methylation and hyaluronidase activity as noninvasive tests for diagnosis of bladder cancer.

PubMed

Eissa, Sanaa; Zohny, Samir F; Shehata, Hanan Hussien; Hegazy, Marwa G A; Salem, Ahmed M; Esmat, Mohamed

2012-04-01

We evaluated the significance of urinary retinoic acid receptor-β2 (RAR-β2) gene promoter methylation and hyaluronidase activity in comparison with voided urine cytology (VUC) in diagnosis of bladder cancer. This study included 100 patients diagnosed with bladder cancer, 65 patients with benign urological disorders and 51 healthy volunteers. Urine supernatant was used for determining hyaluronidase activity by zymography while urine sediment was used for cytology and detection of methylated RAR-β2 gene promoter by methylation specific nested PCR. The sensitivity and specificity were 53% and 90.5% for VUC, 65% and 89.7% for percent methylation fraction of RAR-β2 gene promoter, and 89% and 90.5% for hyaluronidase activity; combination of the three parameters increased sensitivity to 95%. A significant association was observed between investigated markers and advanced grade tumor. Combined use of RAR-β2 gene promoter methylation, hyaluronidase activity and VUC is promising non-invasive tool for bladder cancer detection. Copyright © 2012. Published by Elsevier Inc.

Large-Scale SRM Screen of Urothelial Bladder Cancer Candidate Biomarkers in Urine.

PubMed

Duriez, Elodie; Masselon, Christophe D; Mesmin, Cédric; Court, Magali; Demeure, Kevin; Allory, Yves; Malats, Núria; Matondo, Mariette; Radvanyi, François; Garin, Jérôme; Domon, Bruno

2017-04-07

Urothelial bladder cancer is a condition associated with high recurrence and substantial morbidity and mortality. Noninvasive urinary tests that would detect bladder cancer and tumor recurrence are required to significantly improve patient care. Over the past decade, numerous bladder cancer candidate biomarkers have been identified in the context of extensive proteomics or transcriptomics studies. To translate these findings in clinically useful biomarkers, the systematic evaluation of these candidates remains the bottleneck. Such evaluation involves large-scale quantitative LC-SRM (liquid chromatography-selected reaction monitoring) measurements, targeting hundreds of signature peptides by monitoring thousands of transitions in a single analysis. The design of highly multiplexed SRM analyses is driven by several factors: throughput, robustness, selectivity and sensitivity. Because of the complexity of the samples to be analyzed, some measurements (transitions) can be interfered by coeluting isobaric species resulting in biased or inconsistent estimated peptide/protein levels. Thus the assessment of the quality of SRM data is critical to allow flagging these inconsistent data. We describe an efficient and robust method to process large SRM data sets, including the processing of the raw data, the detection of low-quality measurements, the normalization of the signals for each protein, and the estimation of protein levels. Using this methodology, a variety of proteins previously associated with bladder cancer have been assessed through the analysis of urine samples from a large cohort of cancer patients and corresponding controls in an effort to establish a priority list of most promising candidates to guide subsequent clinical validation studies.

miR-1182 inhibits growth and mediates the chemosensitivity of bladder cancer by targeting hTERT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Jun; Dai, Wenbin, E-mail: daiwenbin271@163.com; Song, Jianming

2016-02-05

microRNAs (miRNAs) have been demonstrated to contribute to tumor progression and metastasis and proposed to be key regulators of diverse biological processes. In this study, we report that miR-1182 is deregulated in bladder cancer tissues and cell lines. To characterize the role of miR-1182 in bladder cancer cells, we performed functional assays. The overexpression of miR-1182 significantly inhibits bladder cancer cell proliferation, colony formation, and invasion. Moreover, its up-regulation induced cell cycle arrest and apoptosis and mediated chemosensitivity to cisplatin in bladder cancer. Furthermore, a luciferase reporter assay and a rescue experiment indicated that miR-1182 directly targets hTERT by bindingmore » its 3′UTR. In conclusion, these results demonstrate that miR-1182 acts as a tumor suppressor and may be a potential biomarker for bladder cancer diagnosis and treatment.« less

Urinary bladder cancer T-staging from T2-weighted MR images using an optimal biomarker approach

NASA Astrophysics Data System (ADS)

Wang, Chuang; Udupa, Jayaram K.; Tong, Yubing; Chen, Jerry; Venigalla, Sriram; Odhner, Dewey; Guzzo, Thomas J.; Christodouleas, John; Torigian, Drew A.

2018-02-01

Magnetic resonance imaging (MRI) is often used in clinical practice to stage patients with bladder cancer to help plan treatment. However, qualitative assessment of MR images is prone to inaccuracies, adversely affecting patient outcomes. In this paper, T2-weighted MR image-based quantitative features were extracted from the bladder wall in 65 patients with bladder cancer to classify them into two primary tumor (T) stage groups: group 1 - T stage < T2, with primary tumor locally confined to the bladder, and group 2 - T stage < T2, with primary tumor locally extending beyond the bladder. The bladder was divided into 8 sectors in the axial plane, where each sector has a corresponding reference standard T stage that is based on expert radiology qualitative MR image review and histopathologic results. The performance of the classification for correct assignment of T stage grouping was then evaluated at both the patient level and the sector level. Each bladder sector was divided into 3 shells (inner, middle, and outer), and 15,834 features including intensity features and texture features from local binary pattern and gray-level co-occurrence matrix were extracted from the 3 shells of each sector. An optimal feature set was selected from all features using an optimal biomarker approach. Nine optimal biomarker features were derived based on texture properties from the middle shell, with an area under the ROC curve of AUC value at the sector and patient level of 0.813 and 0.806, respectively.

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

PubMed Central

Quirk, Jeffrey T; Li, Qiang; Natarajan, Nachimuthu; Mettlin, Curtis J; Cummings, K Michael

2004-01-01

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. PMID:19570280

Microplate magnetic chemiluminescence immunoassay for detecting urinary survivin in bladder cancer.

PubMed

Chang, Yanli; Xu, Jianjun; Zhang, Qingyun

2017-10-01

Survivin is a tumor marker for bladder cancer; however the role of urinary survivin levels has not been fully elucidated due to the limitations of current detection methods. Based on two survivin-specific monoclonal antibodies (McAbs) already confirmed through enzyme linked immunosorbent assays, the present study aimed to establish a microplate magnetic chemiluminescence immunoassay (CLIA) for the detection of urinary survivin levels and evaluate its application for the diagnosis of patients with bladder cancer. Horseradish peroxidase and biotin conjugates were used to label two different anti-survivin McAbs, respectively. The labeled antibodies combined with survivin to form a sandwiched immune complex. The streptavidin magnetic particles (MPs) served as the solid phase and the separator. The relevant parameters involved in the immunoassay, including the immunoassay reagents used and the physicochemical parameters were optimized. Then, urine samples from 130 patients with bladder cancer and 113 healthy controls were detected, and analyzed using the established method. The method was linear to 1,000 ng/ml survivin with a detection limit of 0.83 ng/ml. The intra- and inter-assay coefficients of variation were <8, and <11%, respectively. The concentration of diluted survivin and the dilution ratios gave a linear correlation of 0.9989. The results demonstrated that the urinary survivin levels in patients with bladder cancer were significantly higher (P<0.001) compared with that in healthy controls. At a survivin concentration of 2.0884 ng/ml, the sensitivity and specificity were 86.9 and 61.9%, respectively. Furthermore, the urinary survivin levels were positively correlated with metastatic stage, histological stage and recurrence (P<0.01). In conclusion, the present study preliminarily proposed a microplate magnetic CLIA for survivin detection and further evaluated the value of urinary survivin as a diagnostic marker for bladder cancer.

Microplate magnetic chemiluminescence immunoassay for detecting urinary survivin in bladder cancer

PubMed Central

Chang, Yanli; Xu, Jianjun; Zhang, Qingyun

2017-01-01

Survivin is a tumor marker for bladder cancer; however the role of urinary survivin levels has not been fully elucidated due to the limitations of current detection methods. Based on two survivin-specific monoclonal antibodies (McAbs) already confirmed through enzyme linked immunosorbent assays, the present study aimed to establish a microplate magnetic chemiluminescence immunoassay (CLIA) for the detection of urinary survivin levels and evaluate its application for the diagnosis of patients with bladder cancer. Horseradish peroxidase and biotin conjugates were used to label two different anti-survivin McAbs, respectively. The labeled antibodies combined with survivin to form a sandwiched immune complex. The streptavidin magnetic particles (MPs) served as the solid phase and the separator. The relevant parameters involved in the immunoassay, including the immunoassay reagents used and the physicochemical parameters were optimized. Then, urine samples from 130 patients with bladder cancer and 113 healthy controls were detected, and analyzed using the established method. The method was linear to 1,000 ng/ml survivin with a detection limit of 0.83 ng/ml. The intra- and inter-assay coefficients of variation were <8, and <11%, respectively. The concentration of diluted survivin and the dilution ratios gave a linear correlation of 0.9989. The results demonstrated that the urinary survivin levels in patients with bladder cancer were significantly higher (P<0.001) compared with that in healthy controls. At a survivin concentration of 2.0884 ng/ml, the sensitivity and specificity were 86.9 and 61.9%, respectively. Furthermore, the urinary survivin levels were positively correlated with metastatic stage, histological stage and recurrence (P<0.01). In conclusion, the present study preliminarily proposed a microplate magnetic CLIA for survivin detection and further evaluated the value of urinary survivin as a diagnostic marker for bladder cancer. PMID:28943911

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Paul-Yann; Lin, Yung-Lun; Huang, Chin-Chin

Epidemiological studies have revealed that exposure to an arsenic-contaminated environment correlates with the incidence of bladder cancer. Bladder cancer is highly recurrent after intravesical therapy, and most of the deaths from this disease are due to invasive metastasis. In our present study, the role of inorganic arsenic in bladder carcinogenesis is characterized in a mouse model. This work provides the first evidence that inorganic arsenic in drinking water promotes N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder tissue damage, including the urothelium and submucosal layer. This damage to the bladder epithelium induced by BBN includes thickening of the submucosal layer, the loss of the glycosaminoglycanmore » layer and an increase in both the deoxyguanosine oxidation and cytosine methylation levels in the DNA. Further, when 10 ppm inorganic arsenic is combined with BBN, the number of bladder submucosal capillaries is increased. In addition, inorganic arsenic also increases the deoxyguanosine oxidation level, alters the cytosine methylation state, decreases the activities of glutathione reductase and glucose-6-phosphate dehydrogenase, decreases the protein expression of NAD(P)H quinone oxidoreductase-1 (NQO-1) and increases the protein expression of specific protein 1 (Sp1) in bladder tissues. In summary, our data reveal that inorganic arsenic in drinking water promotes the BBN-induced pre-neoplastic damage of bladder tissue in mice, and that the 8-hydroxy-2′-deoxyguanosine, 5-methylcytosine, NQO-1 protein and Sp1 protein levels may be pre-neoplastic markers of bladder tumors. -- Highlights: ► The role of inorganic arsenic in bladder carcinogenesis is characterized in mice. ► We examine the changes in the histology and biochemistry of bladder tissues. ► Inorganic arsenic enhances BBN-induced DNA oxidation while decreases BBN-induced DNA methylation in the mouse bladder. ► Inorganic arsenic alters the activities of the anti-oxidant enzymes in the mouse bladder. ► Inorganic arsenic increases Sp1 while decreases NQO-1 protein expression in the mouse whole bladder.« less

Receptor-targeted therapy of human experimental urinary bladder cancers with cytotoxic LH-RH analog AN-152 [AEZS- 108].

PubMed

Szepeshazi, Karoly; Schally, Andrew V; Keller, Gunhild; Block, Norman L; Benten, Daniel; Halmos, Gabor; Szalontay, Luca; Vidaurre, Irving; Jaszberenyi, Miklos; Rick, Ferenc G

2012-07-01

Many bladder cancers progress to invasion with poor prognosis; new therapeutic methods are needed. We developed a cytotoxic LH-RH analog, AN-152 (AEZS-108) containing doxorubicin (DOX), for targeted therapy of cancers expressing LHRH receptors. We investigated the expression of LH-RH receptors in clinical bladder cancers and in HT-1376, J82, RT-4 and HT-1197 human bladder cancer lines. The effect of analog, AN-152, on growth of these tumor lines xenografted into nude mice was analyzed. Using molecular and functional assays, we also evaluated the differences between the effects of AN-152, and DOX alone. We demonstrated the expression of LH-RH receptors on 18 clinical bladder cancers by immunohistochemistry and on four human urinary bladder cancer lines HT-1376, J82, RT-4 and HT-1197 by Western blotting and binding assays. AN-152 powerfully inhibited growth of these bladder cancers in nude mice. AN-152 exerted greater effects than DOX and was less toxic. DOX activated strong multidrug resistance mechanisms in RT-4 and HT-1197 cancers, while AN-152 had no or less such effect. PCR assays and in vitro studies revealed differences in the action of AN-152 and DOX on the expression of genes involved in apoptosis. These results suggest that targeted cytotoxic LH-RH analog, AN-152 (AEZS- 108), should be examined for treatment of patients with LH-RH receptor positive invasive bladder cancers.

Pitfalls and Limitations of Diffusion-Weighted Magnetic Resonance Imaging in the Diagnosis of Urinary Bladder Cancer

PubMed Central

Lin, Wei-Ching; Chen, Jeon-Hor

2015-01-01

Adequately selecting a therapeutic approach for bladder cancer depends on accurate grading and staging. Substantial inaccuracy of clinical staging with bimanual examination, cystoscopy, and transurethral resection of bladder tumor has facilitated the increasing utility of magnetic resonance imaging to evaluate bladder cancer. Diffusion-weighted imaging (DWI) is a noninvasive functional magnetic resonance imaging technique. The high tissue contrast between cancers and surrounding tissues on DWI is derived from the difference of water molecules motion. DWI is potentially a useful tool for the detection, characterization, and staging of bladder cancers; it can also monitor posttreatment response and provide information on predicting tumor biophysical behaviors. Despite advancements in DWI techniques and the use of quantitative analysis to evaluate the apparent diffusion coefficient values, there are some inherent limitations in DWI interpretation related to relatively poor spatial resolution, lack of cancer specificity, and lack of standardized image acquisition protocols and data analysis procedures that restrict the application of DWI and reproducibility of apparent diffusion coefficient values. In addition, inadequate bladder distension, artifacts, thinness of bladder wall, cancerous mimickers of normal bladder wall and benign lesions, and variations in the manifestation of bladder cancer may interfere with diagnosis and monitoring of treatment. Recognition of these pitfalls and limitations can minimize their impact on image interpretation, and carefully applying the analyzed results and combining with pathologic grading and staging to clinical practice can contribute to the selection of an adequate treatment method to improve patient care. PMID:26055180

Urothelial bladder cancer with cavitary lung metastases

PubMed Central

Kurian, Anil; Lee, Jason; Born, Abraham

2011-01-01

Transitional cell carcinoma (TCC) of the bladder tends to remain superficial; however, in 5% to 20% of cases, it progresses to muscle invasion and, more rarely, can metastasize. TCC of the bladder primarily spreads via regional lymphatics. The most common sites of distant metastases of TCC are the liver, lung, mediastinum and bone. Long-term survival of patients with metastatic bladder cancer is rare. Patterns of pulmonary metastasis include multiple nodules, a solitary mass or interstitial micronodule. When multiple nodules are present, they are round and well-circumscribed, without calcification or cavitation. An unusual case of rapidly metastatic TCC to the lung causing large cavitary masses and nodules is presented. Imaging performed after the patient began chemotherapy revealed widespread necrosis of the metastatic cavitary masses causing moderate volume hemoptysis. PMID:21766082

Is whole-body fluorine-18 fluorodeoxyglucose PET/CT plus additional pelvic images (oral hydration-voiding-refilling) useful for detecting recurrent bladder cancer?

PubMed

Yang, Zhongyi; Cheng, Jingyi; Pan, Lingling; Hu, Silong; Xu, Junyan; Zhang, Yongping; Wang, Mingwei; Zhang, Jianping; Ye, Dingwei; Zhang, Yingjian

2012-08-01

Because of the urinary excretion of fluorine-18 fluorodeoxyglucose ((18)F-FDG), FDG-PET or PET/CT is thought of little value in patients with bladder cancer. The purpose of our study was to investigate the value of (18)F-FDG PET/CT with additional pelvic images in detection of recurrent bladder cancers. From December 2006 to August 2010, 35 bladder cancer patients (median age 56 years old, ranging from 35 to 96) underwent routine (18)F-FDG PET/CT. To better detect bladder lesions, a new method called as oral hydration-voiding-refilling was introduced, which included that all the patients firstly received oral hydration, then were required to void frequently and finally were demanded to hold back urine when the additional pelvic images were scanned. Lesions were confirmed by either histopathology or clinical follow-up for at least 6 months. Finally, 12 recurrent cases of 35 patients were confirmed by cystoscope. PET/CT correctly detected 11 of them. Among these 11 true positive patients, 5 patients (45.5 %) were detected only after additional pelvic images. Lichenoid lesions on the bladder wall were missed, which caused 1 false negative result. All three false positive cases were testified to be inflammatory tissues by cystoscope. Therefore, the sensitivity, specificity and accuracy of PET/CT were 91.7 % (11/12), 87.0 % (20/23) and 88.6 % (31/35), respectively. PET/CT with additional pelvic images can highly detect recurrent lesions in residual bladder tissues. Our method with high accuracy and better endurance could be potentially applied.

Treatment May Help Prevent Bladder Cancer Recurrences

Cancer.gov

Flushing the bladder with the chemotherapy drug gemcitabine after tumors have been removed surgically may reduce the risk of the cancer returning, according to the results of a large clinical trial. As this Cancer Currents blog post explains, the treatment approach is for patients with low-grade bladder cancer.

Identification of Carbonic Anhydrase IX as a Novel Target for Endoscopic Molecular Imaging of Human Bladder Cancer.

PubMed

Wang, Jiaqi; Fang, Ruizhe; Wang, Lu; Chen, Guang; Wang, Hongzhi; Wang, Zhichao; Zhao, Danfeng; Pavlov, Valentin N; Kabirov, Ildar; Wang, Ziqi; Guo, Pengyu; Peng, Li; Xu, Wanhai

2018-06-27

Emerging novel optical imaging techniques with cancer-specific molecular imaging agents offer a powerful and promising platform for cancer detection and resection. White-light cystoscopy and random bladder biopsies remain the most appropriate but nonetheless suboptimal diagnostic technique for bladder cancer, which is associated with high morbidity and recurrence. However, white-light cystoscopy has intrinsic shortcomings. Although current optical imaging technologies hold great potential for improved diagnostic accuracy, there are few imaging agents for specific molecular targeting. Carbonic anhydrase IX (CAIX) plays a pivotal role in tumorigenesis and tumor progression with potential value as an imaging target. Here, we investigated the feasibility of CAIX as a target and validated the diagnostic performance and significance of CAIX as an imaging agent. We first analyzed the data from The Cancer Genome Atlas (TCGA). Pairs of samples comprising bladder cancer and adjacent normal tissue were collected. All tissue samples were used for real-time PCR and immunohistochemistry to compare CAIX expression in normal and cancer tissue. Using blue-light cystoscopy, we observed the optical distribution of fluorescently labeled CAIX antibody in freshly excised human bladders and obtained random bladder biopsies to assess sensitivity and specificity. The TCGA data revealed that CAIX expression was significantly higher in bladder cancer specimens than in normal tissue. The outcome was similar in quantitative real-time PCR analysis. In immunohistochemical analysis, bladder cancer specimens classified in four pathological subtypes presented a variety of positive staining intensities, whereas no benign specimens showed CAIX staining. Using blue-light cystoscopy, we distinguished bladder cancers that were mainly papillary, some variants of urothelial carcinoma, and less carcinoma in situ, from benign tissue, despite the presence of suspicious-appearing mucosa. The sensitivity and specificity for CAIX-targeted imaging were 88.00% and 93.75%, respectively. CAIX-targeted molecular imaging could be a feasible and adaptive alternative approach for the accurate diagnosis and complete resection of bladder cancer. © 2018 The Author(s). Published by S. Karger AG, Basel.

MMP-1 and Pro-MMP-10 as potential urinary pharmacodynamic biomarkers of FGFR3-targeted therapy in patients with bladder cancer.

PubMed

Du, Xiangnan; Lin, Benjamin C; Wang, Qian-Rena; Li, Hao; Ingalla, Ellen; Tien, Janet; Rooney, Isabelle; Ashkenazi, Avi; Penuel, Elicia; Qing, Jing

2014-12-15

The aim of this study was to identify noninvasive pharmacodynamic biomarkers of FGFR3-targeted therapies in bladder cancer to facilitate the clinical development of experimental agent targeting FGFR3. Potential soluble pharmacodynamic biomarkers of FGFR3 were identified using a combination of transcriptional profiling and biochemical analyses in preclinical models. Two matrix metalloproteinases (MMP), MMP-1 and MMP-10, were selected for further studies in human bladder cancer xenograft models treated with a specific anti-FGFR3 monoclonal antibody, R3Mab. Serum and urinary levels of MMP-1 and MMP-10 were determined in healthy donors and patients with bladder cancer. The modulation of MMP-1 and MMP-10 by R3Mab in patients with bladder cancer was further evaluated in a phase I dose-escalation study. MMP-1 and MMP-10 mRNA and protein were downmodulated by FGFR3 shRNA and R3Mab in bladder cancer cell lines. FGFR3 signaling promoted the expression and secretion of MMP-1 and pro-MMP-10 in a MEK-dependent fashion. In bladder cancer xenograft models, R3Mab substantially blocked tumor progression and reduced the protein levels of human MMP-1 and pro-MMP-10 in tumor tissues as well as in mouse serum. Furthermore, both MMP-1 and pro-MMP-10 were elevated in the urine of patients with advanced bladder cancer. In a phase I dose-escalation trial, R3Mab administration resulted in an acute reduction of urinary MMP-1 and pro-MMP-10 levels in patients with bladder cancer. These findings reveal a critical role of FGFR3 in regulating MMP-1 and pro-MMP-10 expression and secretion, and identify urinary MMP-1 and pro-MMP-10 as potential pharmacodynamic biomarkers for R3Mab in patients with bladder cancer. ©2014 American Association for Cancer Research.

Exercise Decreases and Smoking Increases Bladder Cancer Mortality.

PubMed

Liss, Michael A; White, Martha; Natarajan, Loki; Parsons, J Kellogg

2017-06-01

The aim of this study was to investigate modifiable lifestyle factors of smoking, exercise, and obesity with bladder cancer mortality. We used mortality-linked data from the National Health Information Survey from 1998 through 2006. The primary outcome was bladder cancer-specific mortality. The primary exposures were self-reported smoking status (never- vs. former vs. current smoker), self-reported exercise (dichotomized as "did no exercise" vs. "light, moderate, or vigorous exercise in ≥ 10-minute bouts"), and body mass index. We utilized multivariable adjusted Cox proportional hazards regression models, with delayed entry to account for age at survey interview. Complete data were available on 222,163 participants, of whom 96,715 (44%) were men and 146,014 (66%) were non-Hispanic whites, and among whom we identified 83 bladder cancer-specific deaths. In multivariate analyses, individuals who reported any exercise were 47% less likely (adjusted hazard ratio [HR adj ], 0.53; 95% confidence interval [CI], 0.29-0.96; P = .038) to die of bladder cancer than "no exercise". Compared with never-smokers, current (HR adj , 4.24; 95% CI, 1.89-9.65; P = .001) and former (HR adj , 2.95; 95% CI, 1.50-5.79; P = .002) smokers were 4 and 3 times more likely, respectively, to die of bladder cancer. There were no significant associations of body mass index with bladder cancer mortality. Exercise decreases and current smoking increases the risk of bladder cancer-specific mortality. These data suggest that exercise and smoking cessation interventions may reduce bladder cancer death. Published by Elsevier Inc.

Urinary bladder cancer risk factors in an area of former coal, iron, and steel industries in Germany.

PubMed

Krech, Eugen; Selinski, Silvia; Blaszkewicz, Meinolf; Bürger, Hannah; Kadhum, Thura; Hengstler, Jan G; Truss, Michael C; Golka, Klaus

2017-01-01

This study was performed to investigate the frequency of bladder cancer in patients with an occupational history such as underground hard coal mining and/or painting after the structural change in the local industry. A total of 206 patients with bladder cancer and 207 controls were enlisted regarding occupational and nonoccupational bladder cancer risk factors by questionnaire. The phase II enzymes N-acetyltransferase 2 (NAT2), glutathione S-transferases M1 (GSTM1), and T1 (GSTT1) and the single nucleotide polymorphism (SNP) rs11892031[A/C] reported to be associated with bladder cancer in genome-wide association studies were genotyped. The bladder cancer risk in varnishers and underground hard coal miners was increased as previously shown in a study in this area performed in the 1980s. The occupation of a car mechanic was associated with a significantly elevated bladder cancer risk and higher in the case of underground hard coal miners even though the mine was closed in 1987. The frequency of GSTM1 negative genotype was comparable in cases and controls (53% versus 54%). In the case of NAT2, the slow NAT2 genotype was more frequent (62% versus 58%) and ultra-slow NAT2 genotype (NAT2*6A and/or *7B alleles only) was 23% versus 15%. An occupational history of a varnisher or an underground hard coal miner remains a risk factor for bladder cancer occurrence. Data indicate that in the case of bladder cancer, GSTM1 is a susceptibility factor related to environmental and/or occupational exposure.

Intravesical Toll-like receptor 7 agonist R-837: Optimization of its formulation in an orthotopic mouse model of bladder cancer

PubMed Central

Hayashi, Tomoko; Crain, Brian; Corr, Maripat; Chan, Michael; Cottam, Howard B; Maj, Roberto; Barberis, Alcide; Leoni, Lorenzo; Carson, Dennis A

2013-01-01

Objective To study the immune response caused by the intravesical administration of the immunomodulator R-837 in various formulations and to estimate its therapeutic potential for bladder cancer. Methods Female C57BL/6 mice were intravesically treated with different formulations of R-837, a Toll-like receptor 7 agonist used for treating genital warts and skin malignancy. The tested formulation mixtures contained different ratios of lactic acid, a thermosensitive poloxamer polymer (Lutrol F127) and 2-(hydroxypropyl)-β-cyclodextrin (HPβCD). Induction of tumor necrosis factor α (TNFα) and keratinocyte-derived chemokine (KC) was analyzed by Luminex microbeads assay. The therapeutic potential of intravesical administration of R-837 was assessed in an orthotopic, syngeneic mouse model of bladder cancer using MB49 cells. Results Intravesical administration of R-837 in lactic acid alone induced systemic and bladder TNFα and KC in a dose-dependent manner. Formulations including poloxamer decreased systemic absorption of R-837 and significantly reduced systemic and local induction of KC. Addition of HPβCD in the poloxamer formulation particularly reversed levels of systemic and local levels of TNFα and KC. Histological examination showed that poloxamer-HPβCD formulation allowed infiltration of mononuclear cells into urothelium and lamina propria. In studies using orthotopic mouse bladder cancer, the tumor loads in R-837-treated mice were significantly lower than those in vehicle-treated or non-treated mice. Conclusion The optimized poloxamer-HPβCD formulation of R-837 shows therapeutic potential for bladder cancer while avoiding adverse side-effects. PMID:20337728

Clinical value and potential pathways of miR-183-5p in bladder cancer: A study based on miRNA-seq data and bioinformatics analysis

PubMed Central

Gao, Jia-Min; Huang, Lin-Zhen; Huang, Zhi-Guang; He, Rong-Quan

2018-01-01

The clinicopathological value and exploration of the potential molecular mechanism of microRNA-183-5p (miR-183-5p) have been investigated in various cancers; however, to the best of the author's knowledge, no similar research has been reported for bladder cancer. In the present study, it was revealed that the expression level of miR-183-5p was notably increased in bladder cancer tissues compared with adjacent non-cancerous tissues (P=0.001) and was markedly increased in the tissue samples of papillary, pathological T stage (T0-T2) and pathological stage (I–II) compared with tissue samples of their counterparts (P=0.05), according to data from The Cancer Genome Atlas. Receiver operating characteristic analysis revealed the robust diagnostic value of miR-183-5p for distinguishing bladder cancer from non-cancerous bladder tissues (area under curve=0.948; 95% confidence interval: 0.919–0.977). Amplification and deep deletion of miR-183-5p were indicated by cBioPortal, accounting for 1% (4/412) of bladder cancer cases. Data from YM500v3 demonstrated that compared with other cancers, bladder cancer exhibited high expression levels of miR-183-5p, and miR-183-5p expression in primary solid tumors was much higher compared with solid normal tissues. A meta-analysis indicated that miR-183-5p was more highly expressed in bladder cancer samples compared with normal counterparts. A total of 88 potential target genes of miR-183-5p were identified, 13 of which were discerned as hub genes by protein-protein interaction. The epithelial-to-mesenchymal transition pathway was the most significantly enriched pathway by FunRich (P=0.0001). In summary, miR-183-5p may participate in the tumorigenesis and development of bladder cancer via certain signaling pathways, particularly the epithelial-to-mesenchymal transition pathway. However, the exact molecular mechanism of miR-183-5p in bladder cancer must be validated by in vitro and in vivo experiments. PMID:29616090

Clinical value and potential pathways of miR-183-5p in bladder cancer: A study based on miRNA-seq data and bioinformatics analysis.

PubMed

Gao, Jia-Min; Huang, Lin-Zhen; Huang, Zhi-Guang; He, Rong-Quan

2018-04-01

The clinicopathological value and exploration of the potential molecular mechanism of microRNA-183-5p (miR-183-5p) have been investigated in various cancers; however, to the best of the author's knowledge, no similar research has been reported for bladder cancer. In the present study, it was revealed that the expression level of miR-183-5p was notably increased in bladder cancer tissues compared with adjacent non-cancerous tissues (P=0.001) and was markedly increased in the tissue samples of papillary, pathological T stage (T0-T2) and pathological stage (I-II) compared with tissue samples of their counterparts (P=0.05), according to data from The Cancer Genome Atlas. Receiver operating characteristic analysis revealed the robust diagnostic value of miR-183-5p for distinguishing bladder cancer from non-cancerous bladder tissues (area under curve=0.948; 95% confidence interval: 0.919-0.977). Amplification and deep deletion of miR-183-5p were indicated by cBioPortal, accounting for 1% (4/412) of bladder cancer cases. Data from YM500v3 demonstrated that compared with other cancers, bladder cancer exhibited high expression levels of miR-183-5p, and miR-183-5p expression in primary solid tumors was much higher compared with solid normal tissues. A meta-analysis indicated that miR-183-5p was more highly expressed in bladder cancer samples compared with normal counterparts. A total of 88 potential target genes of miR-183-5p were identified, 13 of which were discerned as hub genes by protein-protein interaction. The epithelial-to-mesenchymal transition pathway was the most significantly enriched pathway by FunRich (P=0.0001). In summary, miR-183-5p may participate in the tumorigenesis and development of bladder cancer via certain signaling pathways, particularly the epithelial-to-mesenchymal transition pathway. However, the exact molecular mechanism of miR-183-5p in bladder cancer must be validated by in vitro and in vivo experiments.

Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of bladder carcinoma.

PubMed

Kamat, Ashish M; Bellmunt, Joaquim; Galsky, Matthew D; Konety, Badrinath R; Lamm, Donald L; Langham, David; Lee, Cheryl T; Milowsky, Matthew I; O'Donnell, Michael A; O'Donnell, Peter H; Petrylak, Daniel P; Sharma, Padmanee; Skinner, Eila C; Sonpavde, Guru; Taylor, John A; Abraham, Prasanth; Rosenberg, Jonathan E

2017-08-15

The standard of care for most patients with non-muscle-invasive bladder cancer (NMIBC) is immunotherapy with intravesical Bacillus Calmette-Guérin (BCG), which activates the immune system to recognize and destroy malignant cells and has demonstrated durable clinical benefit. Urologic best-practice guidelines and consensus reports have been developed and strengthened based on data on the timing, dose, and duration of therapy from randomized clinical trials, as well as by critical evaluation of criteria for progression. However, these reports have not penetrated the community, and many patients do not receive appropriate therapy. Additionally, several immune checkpoint inhibitors have recently been approved for treatment of metastatic disease. The approval of immune checkpoint blockade for patients with platinum-resistant or -ineligible metastatic bladder cancer has led to considerations of expanded use for both advanced and, potentially, localized disease. To address these issues and others surrounding the appropriate use of immunotherapy for the treatment of bladder cancer, the Society for Immunotherapy of Cancer (SITC) convened a Task Force of experts, including physicians, patient advocates, and nurses, to address issues related to patient selection, toxicity management, clinical endpoints, as well as the combination and sequencing of therapies. Following the standard approach established by the Society for other cancers, a systematic literature review and analysis of data, combined with consensus voting was used to generate guidelines. Here, we provide a consensus statement for the use of immunotherapy in patients with bladder cancer, with plans to update these recommendations as the field progresses.

Bladder and Other Urothelial Cancers Screening (PDQ®)—Patient Version

Cancer.gov

Bladder and other urothelial cancers screening is not done routinely in the general population. Not all screening tests are helpful and most have risks. Learn more about bladder cancer risks and screening in this expert-reviewed summary.

NCCN Guidelines Insights: Bladder Cancer, Version 2.2016.

PubMed

Clark, Peter E; Spiess, Philippe E; Agarwal, Neeraj; Bangs, Rick; Boorjian, Stephen A; Buyyounouski, Mark K; Efstathiou, Jason A; Flaig, Thomas W; Friedlander, Terence; Greenberg, Richard E; Guru, Khurshid A; Hahn, Noah; Herr, Harry W; Hoimes, Christopher; Inman, Brant A; Kader, A Karim; Kibel, Adam S; Kuzel, Timothy M; Lele, Subodh M; Meeks, Joshua J; Michalski, Jeff; Montgomery, Jeffrey S; Pagliaro, Lance C; Pal, Sumanta K; Patterson, Anthony; Petrylak, Daniel; Plimack, Elizabeth R; Pohar, Kamal S; Porter, Michael P; Sexton, Wade J; Siefker-Radtke, Arlene O; Sonpavde, Guru; Tward, Jonathan; Wile, Geoffrey; Dwyer, Mary A; Smith, Courtney

2016-10-01

These NCCN Guidelines Insights discuss the major recent updates to the NCCN Guidelines for Bladder Cancer based on the review of the evidence in conjunction with the expert opinion of the panel. Recent updates include (1) refining the recommendation of intravesical bacillus Calmette-Guérin, (2) strengthening the recommendations for perioperative systemic chemotherapy, and (3) incorporating immunotherapy into second-line therapy for locally advanced or metastatic disease. These NCCN Guidelines Insights further discuss factors that affect integration of these recommendations into clinical practice. Copyright © 2016 by the National Comprehensive Cancer Network.

Dysregulation of miRNAs in bladder cancer: altered expression with aberrant biogenesis procedure

PubMed Central

Dong, Fan; Xu, Tianyuan; Shen, Yifan; Zhong, Shan; Chen, Shanwen; Ding, Qiang; Shen, Zhoujun

2017-01-01

Aberrant expression profiles of miRNAs are widely observed in the clinical tissue specimens and urine samples as well as the blood samples of bladder cancer patients. These profiles are closely related to the pathological features of bladder cancer, such as the tumour stage/grade, metastasis, recurrence and chemo-sensitivity. MiRNA biogenesis forms the basis of miRNA expression and function, and its dysregulation has been shown to be essential for variations in miRNA expression profiles as well as tumourigenesis and cancer progression. In this review, we summarize the up-to-date and widely reported miRNAs in bladder cancer that display significantly altered expression. We then compare the miRNA expression profiles among three different sample types (tissue, urine and blood) from patients with bladder cancer. Moreover, for the first time, we outline the dysregulated miRNA biogenesis network in bladder cancer from different levels and analyse its possible relationship with aberrant miRNA expression and the pathological characteristics of the disease. PMID:28187437

Opium and bladder cancer: A systematic review and meta-analysis of the odds ratios for opium use and the risk of bladder cancer

PubMed Central

Afshari, Mahdi; Janbabaei, Ghasem; Bahrami, Mohammad Amin

2017-01-01

Objective The association between opium use and bladder cancer has been investigated in many studies, with varying reporting results reported. This study aims to estimate the total odds ratio for the association between bladder cancer and opium consumption using meta-analysis. Methods The study was designed according to PRISMA guidelines. Two independent researchers searched for the relevant studies using PubMed, Web of Science, Scopus, OVID, Embase, and Google Scholar. After systematic screening of the studies identified during the first step, Cochrane risk of bias tool was determined for the selected studies. The case-control and the cohort studies were investigated to assess risk of bladder cancer due to opium use. In addition, the cross-sectional studies were analysed separately to assess frequency of opium consumption. These estimates were combined using the inverse variance method. Fixed or random effect models were applied to combine the point odds ratios. The heterogeneity between the primary results was assessed using the Cochran test and I-square index. The suspected factors for heterogeneity were investigated using meta-regression models. An Egger test was conducted to identify any probable publication bias. Forest plots illustrated the point and pooled estimates. All analyses were performed using Stata version 14 software and RevMan version 5.3. Results We included 17 primary studies (11 case-control, one cohort and five cross-sectional) in the final meta-analysis. The total odds ratios (95% confidence intervals) for developing bladder cancer by opium use alone, and concurrent use of opium and cigarettes were estimated as 3.85 (3.05–4.87) and 5.7 (1.9–16.3) respectively. The odds ratio (95% confidence interval) for opium use with or without cigarette smoking was estimated as 5.3 (3.6–7.7). Conclusion This meta-analysis showed that opium use similar to cigarette smoking and maybe with similar mechanisms can be a risk factor for bladder cancer. It is therefore expected to be a risk factor for other cancers. PMID:28586371

Non-contrast magnetic resonance imaging for bladder cancer: fused high b value diffusion-weighted imaging and T2-weighted imaging helps evaluate depth of invasion.

PubMed

Lee, Minsu; Shin, Su-Jin; Oh, Young Taik; Jung, Dae Chul; Cho, Nam Hoon; Choi, Young Deuk; Park, Sung Yoon

2017-09-01

To investigate the utility of fused high b value diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) for evaluating depth of invasion in bladder cancer. We included 62 patients with magnetic resonance imaging (MRI) and surgically confirmed urothelial carcinoma in the urinary bladder. An experienced genitourinary radiologist analysed the depth of invasion (T stage <2 or ≥2) using T2WI, DWI, T2WI plus DWI, and fused DWI and T2WI (fusion MRI). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were investigated. Area under the curve (AUC) was analysed to identify T stage ≥2. The rate of patients with surgically confirmed T stage ≥2 was 41.9% (26/62). Sensitivity, specificity, PPV, NPV and accuracy were 50.0%, 55.6%, 44.8%, 60.6% and 53.2%, respectively, with T2WI; 57.7%, 77.8%, 65.2%, 71.8% and 69.4%, respectively, with DWI; 65.4%, 80.6%, 70.8%, 76.3% and 74.2%, respectively, with T2WI plus DWI and 80.8%, 77.8%, 72.4%, 84.9% and 79.0%, respectively, with fusion MRI. AUC was 0.528 with T2WI, 0.677 with DWI, 0.730 with T2WI plus DWI and 0.793 with fusion MRI for T stage ≥2. Fused high b value DWI and T2WI may be a promising non-contrast MRI technique for assessing depth of invasion in bladder cancer. • Accuracy of fusion MRI was 79.0% for T stage ≥2 in bladder cancer. • AUC of fusion MRI was 0.793 for T stage ≥2 in bladder cancer. • Diagnostic performance of fusion MRI was comparable with T2WI plus DWI. • As a non-contrast MRI technique, fusion MRI is useful for bladder cancer.

Reexamination of Total Fluid Intake and Bladder Cancer in the Health Professionals Follow-Up Study Cohort

PubMed Central

Zhou, Jiachen; Smith, Scott; Giovannucci, Edward; Michaud, Dominique S.

2012-01-01

It has been hypothesized that high fluid intake may reduce contact time between carcinogens and bladder epithelium and consequently reduce carcinogenesis. Epidemiologic studies examining fluid intake and bladder cancer have been extremely inconsistent, ranging from strong inverse to strong positive associations. The authors reevaluated the association between fluid intake and bladder cancer among 47,909 participants in the prospective Health Professionals Follow-up Study over a period of 22 years. During follow-up (1986–2008), 823 incident bladder cancer cases were diagnosed. Information on fluid intake was collected by using the food frequency questionnaire at baseline and every 4 years thereafter. Cox proportional hazard regression analysis was used to adjust for risk factors for bladder cancer. Total fluid intake was inversely associated with bladder cancer when the analysis was based on the baseline diet (relative risk = 0.76, 95% confidence interval: 0.60, 0.97), comparing the highest total daily fluid intake quintile (>2,531 mL/day) with the lowest quintile (<1,290 mL/day) (Ptrend = 0.01). However, no association was detected when the analysis was based on recent diet or cumulative updated diet. The updated analysis for total fluid intake and bladder cancer was attenuated compared with the original findings from the first 10-year follow-up period. PMID:22355034

Propensity Score Analysis of Radical Cystectomy Versus Bladder-Sparing Trimodal Therapy in the Setting of a Multidisciplinary Bladder Cancer Clinic.

PubMed

Kulkarni, Girish S; Hermanns, Thomas; Wei, Yanliang; Bhindi, Bimal; Satkunasivam, Raj; Athanasopoulos, Paul; Bostrom, Peter J; Kuk, Cynthia; Li, Kathy; Templeton, Arnoud J; Sridhar, Srikala S; van der Kwast, Theodorus H; Chung, Peter; Bristow, Robert G; Milosevic, Michael; Warde, Padraig; Fleshner, Neil E; Jewett, Michael A S; Bashir, Shaheena; Zlotta, Alexandre R

2017-07-10

Purpose Multidisciplinary management improves complex treatment decision making in cancer care, but its impact for bladder cancer (BC) has not been documented. Although radical cystectomy (RC) currently is viewed as the standard of care for muscle-invasive bladder cancer (MIBC), radiotherapy-based, bladder-sparing trimodal therapy (TMT) that combines transurethral resection of bladder tumor, chemotherapy for radiation sensitization, and external beam radiotherapy has emerged as a valid treatment option. In the absence of randomized studies, this study compared the oncologic outcomes between patients treated with RC or TMT by using a propensity score matched-cohort analysis. Methods Data from patients treated in a multidisciplinary bladder cancer clinic (MDBCC) from 2008 to 2013 were reviewed retrospectively. Those who received TMT for MIBC were identified and matched (for sex, cT and cN stage, Eastern Cooperative Oncology Group status, Charlson comorbidity score, treatment date, age, carcinoma in situ status, and hydronephrosis) with propensity scores to patients who underwent RC. Overall survival and disease-specific survival (DSS) were assessed with Cox proportional hazards modeling and a competing risk analysis, respectively. Results A total of 112 patients with MIBC were included after matching (56 who had been treated with TMT, and 56 who underwent RC). The median age was 68.0 years, and 29.5% had stage cT3/cT4 disease. At a median follow-up of 4.51 years, there were 20 deaths (35.7%) in the RC group (13 as a result of BC) and 22 deaths (39.3%) in the TMT group (13 as a result of BC). The 5-year DSS rate was 73.2% and 76.6% in the RC and TMT groups, respectively ( P = .49). Salvage cystectomy was performed in 6 (10.7%) of 56 patients who received TMT. Conclusion In the setting of a MDBCC, TMT yielded survival outcomes similar to those of matched patients who underwent RC. Appropriately selected patients with MIBC should be offered the opportunity to discuss various treatment options, including organ-sparing TMT.

A novel role for drebrin in regulating progranulin bioactivity in bladder cancer

PubMed Central

Morcavallo, Alaide; Genua, Marco; Shirao, Tomoaki; Peiper, Stephen C.; Gomella, Leonard G.; Birbe, Ruth; Belfiore, Antonino; Iozzo, Renato V.; Morrione, Andrea

2015-01-01

We recently established a critical role for the growth factor progranulin in bladder cancer insofar as progranulin promotes urothelial cancer cell motility and contributes, as an autocrine growth factor, to the transformed phenotype by modulating invasion and anchorage-independent growth. In addition, progranulin expression is upregulated in invasive bladder cancer tissues compared to normal controls. However, the molecular mechanisms of progranulin action in bladder cancer have not been fully elucidated. In this study, we searched for novel progranulin-interacting proteins using pull-down assays with recombinant progranulin and proteomics. We discovered that drebrin, an F-actin binding protein, bound progranulin in urothelial cancer cells. We characterized drebrin function in urothelial cancer cell lines and showed that drebrin is critical for progranulin-dependent activation of the Akt and MAPK pathways and modulates motility, invasion and anchorage-independent growth. In addition, drebrin regulates tumor formation in vivo and its expression is upregulated in bladder cancer tissues compared to normal tissue controls. Our data are translationally relevant as indicate that drebrin exerts an essential functional role in the regulation of progranulin action and may constitute a novel target for therapeutic intervention in bladder tumors. In addition, drebrin may serve as novel biomarker for bladder cancer. PMID:25839164

Genome-wide association studies in bladder cancer: first results and potential relevance.

PubMed

Kiemeney, Lambertus A; Grotenhuis, Anne J; Vermeulen, Sita H; Wu, Xifeng

2009-09-01

The role of genetic susceptibility in the development of urinary bladder cancer is unclear, as it is in many other types of cancer. Since 2007, however, an innovative research approach (i.e. genome-wide association studies or GWASs) has led to the identification of numerous genomic loci that harbor susceptibility factors for one or more cancer sites. All GWASs have been published in high-impact journals and the strengths of the design are acknowledged by all experts, but there is criticism about the relevance of the results. Late 2008, the first GWAS in bladder cancer was published. In this review, the principles of GWASs are explained, as well as their strengths and limitations. The study in bladder cancer among 4000 cases and 38,000 controls identified three new susceptibility loci at 8q24, 3q28, and 5p15 that increase the risk of bladder cancer by 22, 19, and 16%, respectively. The results of two other GWASs in bladder cancer are expected to appear this year. Joint analysis of the three studies will probably identify additional susceptibility loci. The results of bladder cancer GWASs may point the way to yet unknown disease mechanisms. So far, the findings are not sufficiently discriminative for risk predictions to be used in clinical care or public health.

Superficial and muscle-invasive bladder cancer: principles of management for outcomes assessments.

PubMed

Parekh, Dipen J; Bochner, Bernard H; Dalbagni, Guido

2006-12-10

Bladder cancer is a heterogeneous disease. Non-muscle-invasive bladder cancer embraces a spectrum of tumors with varying degrees of clinical behavior. Transurethral resection remains the surgical mainstay for the treatment of non-muscle-invasive bladder cancer. In an attempt to decrease the recurrence or progression rate, intravesical chemotherapy or immunotherapy is also used. Radical cystectomy with bilateral pelvic lymph node dissection remains the gold standard for treating muscle-invasive bladder cancer. Over the last decade, the orthotopic neobladder has gained widespread popularity as the preferred mode of urinary diversion in both males and females with similar oncologic and functional outcomes. Well-designed trials with effective chemotherapy have shown a beneficial role for neoadjuvant chemotherapy.

Veliparib, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Biliary, Pancreatic, Urothelial, or Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-07-01

Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Bladder Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Pancreatic Cancer; Transitional Cell Carcinoma of the Bladder; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

Bladder Cancer in HIV-infected Adults: An Emerging Issue? Case-Reports and Systematic Review.

PubMed

Chawki, Sylvain; Ploussard, Guillaume; Montlahuc, Claire; Verine, Jérome; Mongiat-Artus, Pierre; Desgrandchamps, François; Molina, Jean-Michel

2015-01-01

Non-AIDS-related malignancies now represent a frequent cause of death among HIV-infected patients. Albeit bladder cancer is one of the most common malignancies worldwide, it has been rarely reported among HIV-infected patients. We wished to assess the prevalence and characteristics of bladder cancer in HIV-infected patients. We conducted a single center retrospective study from 1998 to 2013 in a university hospital in Paris. Cases of bladder cancer among HIV-infected patients were identified using the electronic records of the hospital database and of the HIV-infected cohort. Patient characteristics and outcomes were retrieved from patients charts. A systematic review of published cases of bladder cancers in patients with HIV-infection was also performed. During the study period we identified 15 HIV-infected patients (0.2% of the cohort) with a bladder cancer. Patients were mostly men (73%) and smokers (67%), with a median age of 56 years at cancer diagnosis. Bladder cancer was diagnosed a median of 14 years after HIV-infection. Most patients were on ART (86%) with median current and nadir CD4 cell counts of 506 and 195 cells/mm3, respectively. Haematuria (73%) was the most frequent presenting symptom and HPV-associated lesions were seen in 6/10 (60%) patients. Histopathology showed transitional cell carcinoma in 80% and a high proportion of tumors with muscle invasion (47%) and high histologic grade (73%). One-year survival rate was 74.6%. The systematic review identified 13 additional cases of urothelial bladder cancers which shared similar features. Bladder cancers in HIV-infected patients remain rare but may occur in relatively young patients with a low nadir CD4 cell count, have aggressive pathological features and can be fatal.

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

PubMed

Büchner, Frederike L; Bueno-de-Mesquita, H Bas; Ros, Martine M; Kampman, Ellen; Egevad, Lars; Overvad, Kim; Tjønneland, Anne; Roswall, Nina; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Touillaud, Marina; Kaaks, Rudolf; Chang-Claude, Jenny; Boeing, Heiner; Weikert, Steffen; Trichopoulou, Antonia; Naska, Ada; Benetou, Vicky; Palli, Domenico; Sieri, Sabina; Vineis, Paolo; Tumino, Rosario; Panico, Salvatore; van Duijnhoven, Fränzel J B; Peeters, Petra H M; van Gils, Carla H; Lund, Eiliv; Gram, Inger T; Sánchez, Maria-José; Jakszyn, Paula; Larrañaga, Nerea; Ardanaz, Eva; Navarro, Carmen; Rodríguez, Laudina; Manjer, Jonas; Ehrnström, Roy; Hallmans, Göran; Ljungberg, Börje; Key, Tim J; Allen, Naomi E; Khaw, Kay-Tee; Wareham, Nicholas; Slimani, Nadia; Jenab, Mazda; Boffetta, Paolo; Kiemeney, Lambertus A L M; Riboli, Elio

2011-06-15

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 and fruits is associated with bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Detailed data on food consumption and complete follow-up for cancer incidence were available for 452,185 participants, who were recruited from ten European countries. After a mean follow-up of 8.7 years, 874 participants were diagnosed with bladder cancer. Diet diversity scores (DDSs) were used to quantify the variety in fruit and vegetable consumption. Multivariable Cox proportional hazard models were used to assess the effect of the DDSs on bladder cancer risk. There was no evidence of a statistically significant association between bladder cancer risk and any of the DDSs when these scores were considered as continuous covariates. However, the hazard ratio (HR) for the highest tertile of the DDS for combined fruit and vegetable consumption was marginally significant compared to the lowest (HR = 1.30, 95% confidence interval: 1.00-1.69, p-trend = 0.05). In EPIC, there is no clear association between a varied fruit and vegetable consumption and bladder cancer risk. This finding provides further evidence for the absence of any strong association between fruit and vegetable consumption as measured by a food frequency questionnaire and bladder cancer risk. Copyright © 2010 UICC.

MicroRNA-137 Upregulation Increases Bladder Cancer Cell Proliferation and Invasion by Targeting PAQR3

PubMed Central

Xia, Shunyao; Jin, Chengjun; Yin, Huaifu; Zhao, Weiming; Wu, Qiong

2014-01-01

There is increasing evidence suggesting that dysregulation of some microRNAs (miRNAs) may contribute to tumor progression and metastasis and have been proposed to be key regulators of diverse biological processes such as transcriptional regulation, cell growth and tumorigenesis. Previous studies have shown that miR-137 is dysregulated in some malignancies, but its role in bladder cancer is still unknown. In our study, we find that miR-137 is up-regulated in human bladder cancer tissues and cell lines. Moreover, the higher level of miR-137 was associated with pM or pTNM stage in clinical bladder cancer patients. Enforced expression of miR-137 in bladder cancer cells significantly enhanced their proliferation, migration and invasion. Bioinformatics analysis identified the tumor suppressor gene PAQR3 as a potential miR-137 target gene. Further studies indicated that miR-137 suppressed the expression of PAQR3 by binding to its 3′-untranslated region. Silencing of PAQR3 by small interfering RNAs phenocopied the effects of miR-137 overexpression, whereas restoration of PAQR3 in bladder cancer cells bladder cancer cells overexpressing miR-137, partially reversed the suppressive effects of miR-137. These findings indicate that miR-137 could be a potential oncogene in bladder cancer. PMID:25330156

Genetic Variants in the Wnt/β-Catenin Signaling Pathway as Indicators of Bladder Cancer Risk.

PubMed

Pierzynski, Jeanne A; Hildebrandt, Michelle A; Kamat, Ashish M; Lin, Jie; Ye, Yuanqing; Dinney, Colin P N; Wu, Xifeng

2015-12-01

Genetic factors that influence bladder cancer risk remain largely unknown. Previous research has suggested that there is a strong genetic component underlying the risk of bladder cancer. The Wnt/β-catenin signaling pathway is a key modulator of cellular proliferation through its regulation of stem cell homeostasis. Furthermore, variants in the Wnt/β-catenin signaling pathway have been implicated in the development of other cancers, leading us to believe that this pathway may have a vital role in bladder cancer development. A total of 230 single nucleotide polymorphisms in 40 genes in the Wnt/β-catenin signaling pathway were genotyped in 803 bladder cancer cases and 803 healthy controls. A total of 20 single nucleotide polymorphisms were nominally significant for risk. Individuals with 2 variants of LRP6: rs10743980 were associated with a decreased risk of bladder cancer in the recessive model in the initial analysis (OR 0.76, 95% CI 0.58-0.99, p=0.039). This was validated using the bladder genome-wide association study chip (OR 0.51, 95% CI 0.27-1.00, p=0.049 and for combined analysis p=0.007). Together these findings implicate variants in the Wnt/β-catenin stem cell pathway as having a role in bladder cancer etiology. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Bladder/lung cancer mortality in Blackfoot-disease (BFD)-endemic area villages with low (<150 μg/L) well water arsenic levels--an exploration of the dose-response Poisson analysis.

PubMed

Lamm, Steven H; Robbins, Shayhan A; Zhou, Chao; Lu, Jun; Chen, Rusan; Feinleib, Manning

2013-02-01

To examine the analytic role of arsenic exposure on cancer mortality among the low-dose (well water arsenic level <150 μg/L) villages in the Blackfoot-disease (BFD) endemic area of southwest Taiwan and with respect to the southwest regional data. Poisson analyses of the bladder and lung cancer deaths with respect to arsenic exposure (μg/kg/day) for the low-dose (<150 μg/L) villages with exposure defined by the village median, mean, or maximum and with or without regional data. Use of the village median well water arsenic level as the exposure metric introduced misclassification bias by including villages with levels >500 μg/L, but use of the village mean or the maximum did not. Poisson analyses using mean or maximum arsenic levels showed significant negative cancer slope factors for models of bladder cancers and of bladder and lung cancers combined. Inclusion of the southwest Taiwan regional data did not change the findings when the model contained an explanatory variable for non-arsenic differences. A positive slope could only be generated by including the comparison population as a separate data point with the assumption of zero arsenic exposure from drinking water and eliminating the variable for non-arsenic risk factors. The cancer rates are higher among the low-dose (<150 μg/L) villages in the BFD area than in the southwest Taiwan region. However, among the low-dose villages in the BFD area, cancer risks suggest a negative association with well water arsenic levels. Positive differences from regional data seem attributable to non-arsenic ecological factors. Copyright © 2012 Elsevier Inc. All rights reserved.

Therapeutic options for intractable hematuria in advanced bladder cancer.

PubMed

Abt, Dominik; Bywater, Mirjam; Engeler, Daniel Stephan; Schmid, Hans-Peter

2013-07-01

Intractable hematuria is a common and severe complication in patients with inoperable bladder carcinoma. The aim was to provide an overview of therapeutic options for such cases, and analyze their effectiveness and risk profile, so a systematic literature search of peer-reviewed papers published up to September 2012 was carried out. Various options are available to treat hematuria in patients with inoperable bladder cancer; these include orally administered epsilon-aminocaproic acid, intravesical formalin, alum or prostaglandin irrigation, hydrostatic pressure, urinary diversion, radiotherapy, embolization and intraarterial mitoxantrone perfusion. These treatment options are associated with different prospects of success, risks and side-effects. Well-designed and large studies comparing options are completely lacking. Despite various treatment options, management of intractable hematuria in patients with inoperable bladder cancer remains a challenge, and most of the reported methods should be seen as experimental. Interventional radiology and alum instillation seem to be suitable alternative options for patients who, after critical consideration, cannot be treated by irrigation, transurethral resection or palliative cystectomy. © 2013 The Japanese Urological Association.

Investigating Genetic Alterations in Bladder Cancer | Center for Cancer Research

Cancer.gov

Bladder cancer (BC) is the fifth most common cancer worldwide and the sixth most common cancer in the U.S. Mutations in a number of oncogenes and tumor suppressor genes were previously associated with invasive or noninvasive forms of the disease. More recently, next generation sequencing (NGS) of bladder tumors from over 100 Chinese patients revealed alterations in additional

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

PubMed

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. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Spectrophotometric photodynamic detection involving extracorporeal treatment with hexaminolevulinate for bladder cancer cells in voided urine.

PubMed

Nakai, Yasushi; Ozawa, Toshiyuki; Mizuno, Fumiko; Onishi, Sayuri; Owari, Takuya; Hori, Syunta; Morizawa, Yosuke; Tatsumi, Yosihiro; Miyake, Makito; Tanaka, Nobumichi; Tsuruta, Daisuke; Fujimoto, Kiyohide

2017-11-01

To evaluate the feasibility of hexaminolevulinate (HAL) for the photodynamic detection of cancer cells in voided urine. This study included 50 patients with bladder cancer that was confirmed histologically after transurethral resection (bladder cancer group) and 50 outpatients without a history of urothelial carcinoma or cancer-related findings (no malignancy group). One third of the voided urine samples were incubated with aminolevulinic acid (ALA-treated samples), one third were incubated with HAL (HAL-treated samples), and the remaining samples were incubated without treatment (untreated samples). For detecting cellular protoporphyrin IX levels, the intensity of the samples at the excitation wavelength of 405 nm was measured using a spectrophotometer. The difference between the intensity of the ALA-treated or HAL-treated samples and the untreated samples at 635 nm was calculated. HAL-induced fluorescence cytology (HFC) showed that the difference was significantly higher in patients with high-grade tumors than in those with low-grade tumors (p = 0.0003) and the difference was significantly higher in patients with low-grade tumors than in those without a history of urothelial carcinoma or cancer-related findings (p = 0.021). The areas under the receiver operating characteristic curves of ALA-induced fluorescence cytology (AFC) and HFC were 0.77 and 0.81, respectively. The AUC of HFC was significantly higher than that of AFC (p < 0.0001). The overall sensitivity values for conventional cytology, AFC, and HFC were 49, 74, and 74%, respectively. The overall specificity values for AFC and HFC were 70 and 94%, respectively. Spectrophotometric photodynamic detection involving extracorporeal treatment with HAL for bladder cancer cells in voided urine showed high accuracy. This bladder cancer detection method is easy and cost-effective, and has the potential for clinical use.

Cone Beam CT Imaging Analysis of Interfractional Variations in Bladder Volume and Position During Radiotherapy for Bladder Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yee, Don, E-mail: dony@ualberta.c; Parliament, Matthew; Rathee, Satyapal

2010-03-15

Purpose: To quantify daily bladder size and position variations during bladder cancer radiotherapy. Methods and Materials: Ten bladder cancer patients underwent daily cone beam CT (CBCT) imaging of the bladder during radiotherapy. Bladder and planning target volumes (bladder/PTV) from CBCT and planning CT scans were compared with respect to bladder center-of-mass shifts in the x (lateral), y (anterior-posterior), and z (superior-inferior) coordinates, bladder/PTV size, bladder/PTV margin positions, overlapping areas, and mutually exclusive regions. Results: A total of 262 CBCT images were obtained from 10 bladder cancer patients. Bladder center of mass shifted most in the y coordinate (mean, -0.32 cm).more » The anterior bladder wall shifted the most (mean, -0.58 cm). Mean ratios of CBCT-derived bladder and PTV volumes to planning CT-derived counterparts were 0.83 and 0.88. The mean CBCT-derived bladder volume (+- standard deviation [SD]) outside the planning CT counterpart was 29.24 cm{sup 3} (SD, 29.71 cm{sup 3}). The mean planning CT-derived bladder volume outside the CBCT counterpart was 47.74 cm{sup 3} (SD, 21.64 cm{sup 3}). The mean CBCT PTV outside the planning CT-derived PTV was 47.35 cm{sup 3} (SD, 36.51 cm{sup 3}). The mean planning CT-derived PTV outside the CBCT-derived PTV was 93.16 cm{sup 3} (SD, 50.21). The mean CBCT-derived bladder volume outside the planning PTV was 2.41 cm{sup 3} (SD, 3.97 cm{sup 3}). CBCT bladder/ PTV volumes significantly differed from planning CT counterparts (p = 0.047). Conclusions: Significant variations in bladder and PTV volume and position occurred in patients in this trial.« less

Effect of TRPV2 cation channels on the proliferation, migration and invasion of 5637 bladder cancer cells.

PubMed

Liu, Quanliang; Wang, Xinghuan

2013-11-01

Transient receptor potential vanilloid 2 (TRPV2), a nonselective cation channel, has become an attractive target gene for tumor studies due to its wide range of physiological and pathological functions. However, its specific role in bladder cancer development and progression remains unclear. The aim of the present study was to investigate the effects of TRPV2 on the proliferation, migration and invasion of 5637 bladder cancer cells in vitro . Rat TRPV2 cDNA was transfected into 5637 bladder cancer cells and changes in the behavior of the cells were detected. It was observed that TRPV2 enhanced bladder cancer cell migration and invasion; however, it did not affect cell proliferation in vitro . TRPV2 activity, which may be mediated by direct matrix metalloproteinase 2 (MMP2) regulation, is important in bladder tumor development and progression. The results of this study suggest that TRPV2 channels are a potential therapeutic target for bladder carcinoma.

Effect of TRPV2 cation channels on the proliferation, migration and invasion of 5637 bladder cancer cells

PubMed Central

LIU, QUANLIANG; WANG, XINGHUAN

2013-01-01

Transient receptor potential vanilloid 2 (TRPV2), a nonselective cation channel, has become an attractive target gene for tumor studies due to its wide range of physiological and pathological functions. However, its specific role in bladder cancer development and progression remains unclear. The aim of the present study was to investigate the effects of TRPV2 on the proliferation, migration and invasion of 5637 bladder cancer cells in vitro. Rat TRPV2 cDNA was transfected into 5637 bladder cancer cells and changes in the behavior of the cells were detected. It was observed that TRPV2 enhanced bladder cancer cell migration and invasion; however, it did not affect cell proliferation in vitro. TRPV2 activity, which may be mediated by direct matrix metalloproteinase 2 (MMP2) regulation, is important in bladder tumor development and progression. The results of this study suggest that TRPV2 channels are a potential therapeutic target for bladder carcinoma. PMID:24223658

Combination of Rapamycin and Resveratrol for Treatment of Bladder Cancer.

PubMed

Alayev, Anya; Salamon, Rachel S; Schwartz, Naomi S; Berman, Adi Y; Wiener, Sara L; Holz, Marina K

2017-02-01

Loss of TSC1 function, a crucial negative regulator of mTOR signaling, is a common alteration in bladder cancer. Mutations in other members of the PI3K pathway, leading to mTOR activation, are also found in bladder cancer. This provides rationale for targeting mTOR for treatment of bladder cancer characterized by TSC1 mutations and/or mTOR activation. In this study, we asked whether combination treatment with rapamycin and resveratrol could be effective in concurrently inhibiting mTOR and PI3K signaling and inducing cell death in bladder cancer cells. In combination with rapamycin, resveratrol was able to block rapamycin-induced Akt activation, while maintaining mTOR pathway inhibition. In addition, combination treatment with rapamycin and resveratrol induced cell death specifically in TSC1 -/- MEF cells, and not in wild-type MEFs. Similarly, resveratrol alone or in combination with rapamycin induced cell death in human bladder cancer cell lines. These data indicate that administration of resveratrol together with rapamycin may be a promising therapeutic option for treatment of bladder cancer. J. Cell. Physiol. 232: 436-446, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Psorinum Therapy in Treating Stomach, Gall Bladder, Pancreatic, and Liver Cancers: A Prospective Clinical Study

PubMed Central

Chatterjee, Aradeep; Biswas, Jaydip; Chatterjee, Ashim; Bhattacharya, Sudin; Mukhopadhyay, Bishnu; Mandal, Syamsundar

2011-01-01

We prospectively studied the clinical efficacy of an alternative cancer treatment “Psorinum Therapy” in treating stomach, gall bladder, pancreatic and liver cancers. Our study was observational, open level and single arm. The participants' eligibility criteria included histopathology/cytopathology confirmation of malignancy, inoperable tumor, and no prior chemotherapy or radiation therapy. The primary outcome measures of the study were (i) to assess the radiological tumor response (ii) to find out how many participants survived at least 1 year, 2 years, 3 years, 4 years and finally 5 years after the beginning of the study considering each type of cancer. Psorinum-6x was administered orally to all the participants up to 0.02 ml/Kg body weight as a single dose in empty stomach per day for 2 years along with allopathic and homeopathic supportive cares. 158 participants (42 of stomach, 40 of gall bladder, 44 of pancreatic, 32 of liver) were included in the final analysis of the study. Complete tumor response occurred in 28 (17.72%) cases and partial tumor response occurred in 56 (35.44%) cases. Double-blind randomized controlled clinical trial should be conducted for further scientific exploration of this alternative cancer treatment. PMID:21197093

Urinary bladder: normal appearance and mimics of malignancy at CT urography

PubMed Central

Sadow, Cheryl A.; Anik Sahni, V.; Silverman, Stuart G.

2011-01-01

Abstract The objective of this review article is to learn how to recognize anatomic variants and benign entities that mimic bladder cancer at computed tomography (CT) urography. Building on recent data that suggest that CT urography can be used to diagnose bladder cancer, recognition of anatomic variants and benign entities will help improve radiologists’ ability to diagnose bladder cancer. PMID:21771710

Molecular subtype-specific immunocompetent models of high-grade urothelial carcinoma reveal differential neoantigen expression and response to immunotherapy.

PubMed

Saito, Ryoichi; Smith, Christof C; Utsumi, Takanobu; Bixby, Lisa M; Kardos, Jordan; Wobker, Sara E; Stewart, Kyle G; Chai, Shengjie; Manocha, Ujjawal; Byrd, Kevin Matthew; Damrauer, Jeffrey S; Williams, Scott E; Vincent, Benjamin G; Kim, William Y

2018-05-21

High-grade urothelial cancer contains intrinsic molecular subtypes that exhibit differences in underlying tumor biology and can be divided into luminal-like and basal-like subtypes. We describe here the first subtype-specific murine models of bladder cancer and show that Upk3a-CreERT2; Trp53L/L; PtenL/L; Rosa26LSL-Luc (UPPL: luminal-like) and BBN (basal-like) tumors are more faithful to human bladder cancer than the widely-used MB49 cells. Following engraftment into immunocompetent C57BL/6 mice, BBN tumors were more responsive to PD-1 inhibition than UPPL tumors. Responding tumors within the BBN model showed differences in immune microenvironment composition, including increased ratios of CD8+:CD4+ and memory:regulatory T cells. Finally, we predicted and confirmed immunogenicity of tumor neoantigens in each model. These UPPL and BBN models will be a valuable resource for future studies examining bladder cancer biology and immunotherapy. Copyright ©2018, American Association for Cancer Research.

Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer

ClinicalTrials.gov

2018-06-11

Bladder Urothelial Carcinoma; Distal Urethral Carcinoma; Infiltrating Bladder Urothelial Carcinoma Associated With Urethral Carcinoma; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Proximal Urethral Carcinoma; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urethral Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Regional Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer AJCC v7; Stage IV Prostate Cancer AJCC v7; Stage IV Urethral Cancer AJCC v7; Ureter Carcinoma

The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Conde, Vanessa R.; Oliveira, Pedro F.; Department of Microscopy, Laboratory of Cell Biology and Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto – UMIB/ICBAS/UP

Cancer cells present a particular metabolic behavior. We hypothesized that the progression of bladder cancer could be accompanied by changes in cells glycolytic profile. We studied two human bladder cancer cells, RT4 and TCCSUP, in which the latter represents a more invasive stage. The levels of glucose, pyruvate, alanine and lactate in the extracellular media were measured by Proton Nuclear Magnetic Resonance. The protein expression levels of glucose transporters 1 (GLUT1) and 3 (GLUT3), monocarboxylate transporter 4 (MCT4), phosphofructokinase-1 (PFK1), glutamic-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) were determined. Our data showed that glucose consumption and GLUT3 levels were similarmore » in both cell lines, but TCCSUP cells displayed lower levels of GLUT1 and PFK expression. An increase in pyruvate consumption, concordant with the higher levels of lactate and alanine production, was also detected in TCCSUP cells. Moreover, TCCSUP cells presented lower protein expression levels of GPT and LDH. These results illustrate that bladder cancer progression is associated with alterations in cells glycolytic profile, namely the switch from glucose to pyruvate consumption in the more aggressive stage. This may be useful to develop new therapies and to identify biomarkers for cancer progression. - Highlights: • Metabolic phenotype of less and high invasive bladder cancer cells was studied. • Bladder cancer progression involves alterations in cells glycolytic profile. • More invasive bladder cancer cells switch from glucose to pyruvate consumption. • Our results may help to identify metabolic biomarkers of bladder cancer progression.« less

Homing peptide guiding optical molecular imaging for the diagnosis of bladder cancer

NASA Astrophysics Data System (ADS)

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.

Total Fluid and Water Consumption and the Joint Effect of Exposure to Disinfection By-Products on Risk of Bladder Cancer

PubMed Central

Michaud, Dominique S.; Kogevinas, Manolis; Cantor, Kenneth P.; Villanueva, Cristina M.; Garcia-Closas, Monteserrat; Rothman, Nathaniel; Malats, Nuria; Real, Francisco X.; Serra, Consol; Garcia-Closas, Reina; Tardon, Adonina; Carrato, Alfredo; Dosemeci, Mustafa; Silverman, Debra T.

2007-01-01

Background Findings on water and total fluid intake and bladder cancer are inconsistent; this may, in part, be due to different levels of carcinogens in drinking water. High levels of arsenic and chlorinated by-products in drinking water have been associated with elevated bladder cancer risk in most studies. A pooled analysis based on six case–control studies observed a positive association between tap water and bladder cancer but none for nontap fluid intake, suggesting that contaminants in tap water may be responsible for the excess risk. Objectives We examined the association between total fluid and water consumption and bladder cancer risk, as well as the interaction between water intake and trihalomethane (THM) exposure, in a large case–control study in Spain. Methods A total of 397 bladder cancer cases and 664 matched controls were available for this analysis. Odds ratios (OR) were estimated using unconditional logistic regression, controlling for potential confounders. Results Total fluid intake was associated with a decrease in bladder cancer risk [OR = 0.62; 95% confidence interval (CI), 0.40–0.95 for highest vs. lowest quintile comparison]. A significant inverse association was observed for water intake (for > 1,399 vs. < 400 mL/day, OR = 0.47; 95% CI, 0.33–0.66; p for trend < 0.0001), but not for other individual beverages. The inverse association between water intake and bladder cancer persisted within each level of THM exposure; we found no statistical interaction (p for interaction = 0.13). Conclusion Findings from this study suggest that water intake is inversely associated with bladder cancer risk, regardless of THM exposure level. PMID:18007986

Metastasis of Non-Muscle-Invasive Bladder Cancer Into the Thyroid Gland: A Literature Review Accompanied by a Rare Case

PubMed Central

Tuncer, Murat; Faydaci, Gokhan; Altin, Gokhan; Kibar, Sermin; Sanli, Arif; Bilgici, Dilek

2014-01-01

Bladder cancer is the most prevalent malignancy of the urinary tract. About 90% of bladder cancers are urothelial carcinomas. Seventy percent of cases newly diagnosed are superficial diseases; roughly 30% of newly diagnosed cases are muscle-invasive metastatic diseases. Bladder urothelial carcinoma primarily metastasizes into regional lymph nodes and then into liver, lung, mediastinum, bone, and adrenal gland. In our case, non-muscle-invasive bladder cancer metastasized into the bone, mediastinum, iliac lymph node, and adrenal and thyroid glands. This is the first reported case in the current literature in which urothelial carcinoma metastasized into the thyroid gland. PMID:24648880

Nanotechnology in bladder cancer: current state of development and clinical practice

PubMed Central

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. PMID:25929573

Overview of occupational cancer in painters in Korea.

PubMed

Myong, Jun-Pyo; Cho, Younmo; Choi, Min; Kim, Hyoung-Ryoul

2018-01-01

Comprehensive consideration is necessary for setting guidelines to evaluate evidence of occupational cancer in painters due to work-related exposure to carcinogens in paint (a phenomenon termed herein as "work-relatedness"). The aim of the present research is to perform a comprehensive review and to suggest criteria for the provision of compensation for occupational neoplasm among painters in Korea. In order to perform a comprehensive review, this study assessed and evaluated scientific reports of carcinogenicities from the International Agency for Research on Cancer (IARC) and the Industrial Injuries Advisory Council (IIAC), as well as reviewed the existing literature about occupational exposure among painters in Korea and the epidemiologic investigations of claimed cases of cancer among painters in Korea. The IARC declares that occupational exposures in commercial painting are classified as Group 1 carcinogens for lung cancer and bladder cancer among painters. The epidemiologic studies show consistent causal relationships between occupational exposure in painters and cancers such as lung cancer [meta relative risk: 1.34 (95% confidence intervals (CIs): 1.23-1.41)] and bladder cancer [meta relative risk: 1.24 (95% CIs: 1.16-1.33)]. In reviewing occupational cancer risks for commercial painters, the Industrial Injuries Advisory Council (IIAC) confirms occupational cancer risks for lung and bladder cancer among commercial painters. According to the IIAC, however, the elevated cancer risks reported in existing literature are not doubled in either lung or bladder cancer in commercial painters relative to the risks of these cancers in the general population. Based on our review of existing Korean articles on the topic, painters are exposed to potential carcinogens including polycyclic aromatic hydrocarbons (PAHs), benzene, hexavalent chrome, crystalized silica, asbestos, and other agents, and relative levels are estimated within commercial painting processes. However, the cancer risks of occupational exposure to Group 1 carcinogens for lung and bladder cancer in painters per se are not fully assessed in existing Korean articles. Total work duration, potential carcinogens in paint, mixed exposure to paints across various industries such as construction and shipbuilding, exposure periods, latent periods, and other factors should be considered on an individual basis in investigating the work-relatedness of certain types of cancer in commercial painters.

[Concomitant oncopathological changes in the prostate of urinary bladder cancer patients undergoing radical cystoprostateectomy].

PubMed

Komyakov, B K; Sergeev, A V; Fadeev, V A; Ismailov, K I; Ulyanov, A Yu; Shmelev, A Yu; Onoshko, M V

2017-09-01

To determine the incidence of spreading bladder transitional cell carcinoma and primary adenocarcinoma to the prostate in patients with bladder cancer undergoing radical cystectomy. From 1995 to 2016, 283 men underwent radical cystectomy with removal of the bladder, perivesical tissue, prostate, seminal vesicles and pelvic lymph nodes. Prostate sparing cystectomy was performed in 45 (13.7%) patients. The whole prostate and the apex of the prostate were preserved in 21 (6.4%) and 24 (7.3%) patients, respectively. The spread of transitional cell cancer of the bladder to the prostate occurred in 50 (15.2%) patients. Twelve (3.6%) patients were found to have primary prostate adenocarcinoma. Clinically significant prostate cancer was diagnosed in 4 (33.3%) patients. We believe that the high oncological risk of prostate sparing cystectomy, despite some functional advantages, dictates the need for complete removal of the prostate in the surgical treatment of bladder cancer.

Residence in Proximity of a Coal-Oil-Fired Thermal Power Plant and Risk of Lung and Bladder Cancer in North-Eastern Italy. A Population-Based Study: 1995-2009.

PubMed

Collarile, Paolo; Bidoli, Ettore; Barbone, Fabio; Zanier, Loris; Del Zotto, Stefania; Fuser, Simonetta; Stel, Fulvio; Panato, Chiara; Gallai, Irene; Serraino, Diego

2017-07-31

This study investigated the risk of lung and bladder cancers in people residing in proximity of a coal-oil-fired thermal power plant in an area of north-eastern Italy, covered by a population-based cancer registry. Incidence rate ratios (IRR) by sex, age, and histology were computed according to tertiles of residential exposure to benzene, nitrogen dioxide (NO2), particular matter, and sulfur dioxide (SO2) among 1076 incident cases of lung and 650 cases of bladder cancers. In men of all ages and in women under 75 years of age, no significant associations were observed. Conversely, in women aged ≥75 years significantly increased risks of lung and bladder cancers were related to high exposure to benzene (IRR for highest vs. lowest tertile: 2.00 for lung cancer and 1.94 for bladder cancer) and NO2 (IRR: 1.72 for lung cancer; and 1.94 for bladder cancer). In these women, a 1.71-fold higher risk of lung cancer was also related to a high exposure to SO2. Acknowledging the limitations of our study, in particular that we did not have information regarding cigarette smoking habits, the findings of this study indicate that air pollution exposure may have had a role with regard to the risk of lung and bladder cancers limited to women aged ≥75 years. Such increased risk warrants further analytical investigations.

Spatial Analysis of Ambient PM2.5 Exposure and Bladder Cancer Mortality in Taiwan

PubMed Central

Yeh, Hsin-Ling; Hsu, Shang-Wei; Chang, Yu-Chia; Chan, Ta-Chien; Tsou, Hui-Chen; Chang, Yen-Chen; Chiang, Po-Huang

2017-01-01

Fine particulate matter (PM2.5) is an air pollutant that is receiving intense regulatory attention in Taiwan. In previous studies, the effect of air pollution on bladder cancer has been explored. This study was conducted to elucidate the effect of atmospheric PM2.5 and other local risk factors on bladder cancer mortality based on available 13-year mortality data. Geographically weighted regression (GWR) was applied to estimate and interpret the spatial variability of the relationships between bladder cancer mortality and ambient PM2.5 concentrations, and other variables were covariates used to adjust for the effect of PM2.5. After applying a GWR model, the concentration of ambient PM2.5 showed a positive correlation with bladder cancer mortality in males in northern Taiwan and females in most of the townships in Taiwan. This is the first time PM2.5 has been identified as a risk factor for bladder cancer based on the statistical evidence provided by GWR analysis. PMID:28489042

Detecting DNA methylation of the BCL2, CDKN2A and NID2 genes in urine using a nested methylation specific polymerase chain reaction assay to predict bladder cancer.

PubMed

Scher, Michael B; Elbaum, Michael B; Mogilevkin, Yakov; Hilbert, David W; Mydlo, Jack H; Sidi, A Ami; Adelson, Martin E; Mordechai, Eli; Trama, Jason P

2012-12-01

Detection of methylated DNA has been shown to be a good biomarker for bladder cancer. Bladder cancer has the highest recurrence rate of any cancer and, as such, patients are regularly monitored using invasive diagnostic techniques. As urine is easily attainable, bladder cancer is an optimal cancer to detect using DNA methylation. DNA methylation is highly specific in cancer detection. However, it is difficult to detect because of the limited amount of DNA present in the urine of patients with bladder cancer. Therefore, an improved, sensitive and noninvasive diagnostic test is needed. We developed a highly specific and sensitive nested methylation specific polymerase chain reaction assay to detect the presence of bladder cancer in small volumes of patient urine. The genes assayed for DNA methylation are BCL2, CDKN2A and NID2. The regions surrounding the DNA methylation sites were amplified in a methylation independent first round polymerase chain reaction and the amplification product from the first polymerase chain reaction was used in a real-time methylation specific polymerase chain reaction. Urine samples were collected from patients receiving treatment at Wolfson Medical Center in Holon, Israel. In a pilot clinical study using patient urine samples we were able to differentiate bladder cancer from other urogenital malignancies and nonmalignant conditions with a sensitivity of 80.9% and a specificity of 86.4%. We developed a novel methylation specific polymerase chain reaction assay for the detection and monitoring of bladder cancer using DNA extracted from patient urine. The assay may also be combined with other diagnostic tests to improve accuracy. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Previous Bladder Cancer History in Patients with High-Risk, Non-muscle-invasive Bladder Cancer Correlates with Recurrence and Progression: Implications of Natural History.

PubMed

Mitrakas, Lampros P; Zachos, Ioannis V; Tzortzis, Vassileios P; Gravas, Stavros A; Rouka, Erasmia C; Dimitropoulos, Konstantinos I; Vandoros, Gerasimos P; Karatzas, Anastasios D; Melekos, Michael D; Papavassiliou, Athanasios G

2015-07-01

The purpose of this study was to assess the correlation of previous bladder cancer history with the recurrence and progression of patients with high-risk non-muscle-invasive bladder cancer treated with adjuvant Bacillus Calmette-Guérin (BCG) and to evaluate their natural history. Patients were divided into two groups based on the existence of previous bladder cancer (primary, non-primary). A logistic regression analysis was used to identify the possible differences in the probabilities of recurrence and progression with respect to tumor history, while potential differences due to gender, tumor size (> 3 cm, < 3 cm), stage (pTa, T1), concomitant carcinoma in situ (pTis) and number of tumors (single, multiple) were also assessed. Univariate and multivariate models were employed. In addition, Kaplan-Meier survival analysis was used to compare recurrence- and progression-free survival between the groups. A total of 192 patients were included (144 with primary and 48 with non-primary tumors). The rates of recurrence and progression for patients with primary tumors were 27.8% and 12.5%, respectively. The corresponding percentages for patients with non-primary tumors were 77.1% and 33.3%, respectively. The latter group of patients displayed significantly higher probabilities of recurrence (p=0.000; 95% confidence interval [CI], 4.067 to 18.804) and progression (p=0.002; 95% CI, 1.609 to 7.614) in a univariate logistic regression analysis. Previous bladder cancer history remained significant in the multivariate model accounting for history, age, gender, tumor size , number of tumors, stage and concomitant pTis (p=0.000; 95% CI, 4.367 to 21.924 and p=0.002; 95% CI, 1.611 to 8.182 for recurrence and progression respectively). Kaplan-Meier curves revealed that the non-primary group hadreduced progression- and recurrence-free survival. Previous non-muscle-invasive bladder cancer history correlates significantly with recurrence and progression in patients with high-risk non-muscle-invasive disease treated with adjuvant BCG.

N-acetyltransferase 2 gene polymorphism as a biomarker for susceptibility to bladder cancer in Bangladeshi population.

PubMed

Hosen, Md Bayejid; Islam, Jahidul; Salam, Md Abdus; Islam, Md Fakhrul; Hawlader, M Zakir Hossain; Kabir, Yearul

2015-03-01

To investigate the association between the three most common single nucleotide polymorphisms of the N-acetyltransferase 2 gene together with cigarette smoking and the risk of developing bladder cancer and its aggressiveness. A case-control study on 102 bladder cancer patients and 140 control subjects was conducted. The genomic DNA was extracted from peripheral white blood cells and N-acetyltransferase 2 alleles were differentiated by polymerase chain reaction-based restriction fragment length polymorphism methods. Bladder cancer risk was estimated as odds ratio and 95% confidence interval using binary logistic regression models adjusting for age and gender. Overall, N-acetyltransferase 2 slow genotypes were associated with bladder cancer risk (odds ratio=4.45; 95% confidence interval=2.26-8.77). The cigarette smokers with slow genotypes were found to have a sixfold increased risk to develop bladder cancer (odds ratio=6.05; 95% confidence interval=2.23-15.82). Patients with slow acetylating genotypes were more prone to develop high-grade (odds ratio=6.63; 95% confidence interval=1.15-38.13; P<0.05) and invasive (odds ratio=10.6; 95% confidence interval=1.00-111.5; P=0.05) tumor. N-acetyltransferase 2 slow genotype together with tobacco smoking increases bladder cancer risk. Patients with N-acetyltransferase 2 slow genotypes were more likely to develop a high-grade and invasive tumor. N-acetyltransferase 2 slow genotype is an important genetic determinant for bladder cancer in Bangladesh population. © 2014 Wiley Publishing Asia Pty Ltd.

Curcumin inhibits bladder cancer progression via regulation of β-catenin expression.

PubMed

Shi, Jing; Wang, Yunpeng; Jia, Zhuomin; Gao, Yu; Zhao, Chaofei; Yao, Yuanxin

2017-07-01

Bladder cancer has a considerable morbidity and mortality impact with particularly poor prognosis. Curcumin has been recently noticed as a polyphenolic compound separated from turmeric to regulate tumor progression. However, the precise molecular mechanism by which curcumin inhibits the invasion and metastasis of bladder cancer cells is not fully elucidated. In this study, we investigate the effect of curcumin on the bladder cancer as well as possible mechanisms of curcumin. The expression of β-catenin was detected by quantitative real-time polymerase chain reaction and immunohistochemical analysis in a series of bladder cancer tissues. In addition, bladder cancer cell lines T24 and 5637 cells were treated with different concentrations of curcumin. The cytotoxic effect of curcumin on cell proliferation of T24 and 5637 cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The migration and invasion capacity of T24 and 5637 cells were measured by transwell assay. The effects of curcumin on expression levels of β-catenin and epithelial-mesenchymal transition marker were determined by western blotting. The β-catenin expression was significantly upregulated in bladder cancer tissues when compared with corresponding peri-tumor tissues. Furthermore, curcumin inhibited the cell proliferation of T24 and 5637 cells, and curcumin reduced the migration and invasive ability of T24 and 5637 cells via regulating β-catenin expression and reversing epithelial-mesenchymal transition. Curcumin may be a new drug for bladder cancer.

Bladder cancer in patients with spinal cord injury.

PubMed

Hess, Marika J; Zhan, Ellen H; Foo, Dominic K; Yalla, Subbarao V

2003-01-01

The incidence of bladder cancer in spinal cord injury (SCI) is 16 to 28 times higher than that in the general population. The objective of this study was to investigate the characteristics of bladder cancer that are unique to the SCI population. Retrospective review. The charts of 16 patients diagnosed with bladder cancer from 1982 to 2001 were reviewed for type of cancer, exposure to risk factors, presenting symptoms, and survival time. The presenting manifestations were gross hematuria in 14 patients, papillary urethral growth in 1 patient, and acute obstructive renal failure in 1 patient. The diagnosis was made on initial cystoscopic evaluation in 16 patients; 3 patients required further evaluation. Eight of the 11 screening cytologies were suspicious for a malignancy prior to the diagnosis. Seven patients had transitional cell carcinoma, 6 patients had squamous cell carcinoma (SCCA), and 3 patients had both. The bladder wasmanaged with chronic indwelling catheter in 12 patients. Nine patients died of bladder cancer metastases and the remaining 3 patients died of other causes. Six patients survived 5 years or more; 4 were still alive at the completion of this study. Gross hematuria in individuals with SCI warrants aggressive assessment for bladder cancer. Chronic indwelling catheter, smoking, and renal and bladder stones are important risk factors for cancer. The incidence of SCCA in the SCI popullation is much higher than in the general population. Cystoscopic and cytologic evaluation in patients with advanced disease may fail to confirm the diagnosis in a high proportion of patients.

Activation of RAS family genes in urothelial carcinoma.

PubMed

Boulalas, I; Zaravinos, A; Karyotis, I; Delakas, D; Spandidos, D A

2009-05-01

Bladder cancer is the fifth most common malignancy in men in Western society. We determined RAS codon 12 and 13 point mutations and evaluated mRNA expression levels in transitional cell carcinoma cases. Samples from 30 human bladder cancers and 30 normal tissues were analyzed by polymerase chain reaction/restriction fragment length polymorphism and direct sequencing to determine the occurrence of mutations in codons 12 and 13 of RAS family genes. Moreover, we used real-time reverse transcriptase-polymerase chain reaction to evaluate the expression profile of RAS genes in bladder cancer specimens compared to that in adjacent normal tissues. Overall H-RAS mutations in codon 12 were observed in 9 tumor samples (30%). Two of the 9 patients (22%) had invasive bladder cancer and 7 (77%) had noninvasive bladder cancer. One H-RAS mutation (11%) was homozygous and the remaining 89% were heterozygous. All samples were WT for K and N-RAS oncogenes. Moreover, 23 of 30 samples (77%) showed over expression in at least 1 RAS family gene compared to adjacent normal tissue. K and N-RAS had the highest levels of over expression in bladder cancer specimens (50%), whereas 27% of transitional cell carcinomas demonstrated H-RAS over expression relative to paired normal tissues. Our results underline the importance of H-RAS activation in human bladder cancer by codon 12 mutations. Moreover, they provide evidence that increased expression of all 3 RAS genes is a common event in bladder cancer that is associated with disease development.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schulte, P.A.; Ringen, K.; Hemstreet, G.P.

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,more » 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.« less

Associations of dietary carbohydrates, glycaemic index and glycaemic load with risk of bladder cancer: a case-control study.

PubMed

Augustin, Livia S A; Taborelli, Martina; Montella, Maurizio; Libra, Massimo; La Vecchia, Carlo; Tavani, Alessandra; Crispo, Anna; Grimaldi, Maria; Facchini, Gaetano; Jenkins, David J A; Botti, Gerardo; Serraino, Diego; Polesel, Jerry

2017-11-01

Carbohydrate foods with high glycaemic index (GI) and load (GL) may negatively influence cancer risk. We studied the association of dietary carbohydrates, GI, GL, intake of bread and pasta with risk of bladder cancer using data from an Italian case-control study. The study included 578 men and women with histologically confirmed bladder cancer and 608 controls admitted to the same hospitals as cases for acute, non-neoplastic conditions. OR were estimated by logistic regression models after allowance for relevant confounding factors. OR of bladder cancer for the highest v. the lowest quantile of intake were 1·52 (95 % CI 0·85, 2·69) for available carbohydrates, 1·18 (95 % CI 0·83, 1·67) for GI, 1·96 (95 % CI 1·16, 3·31, P trend<0·01) for GL, 1·58 (95 % CI 1·09, 2·29, P trend=0·03) for pasta and 1·92 (95 % CI 1·28, 2·86, P trend<0·01) for bread. OR for regular consumption of legumes and whole-grain products were 0·78 (95 % CI 0·60, 1·00) and 0·82 (95 % CI 0·63, 1·08), respectively. No heterogeneity in risks emerged across strata of sex. This case-control study showed that bladder cancer risk was directly associated with high dietary GL and with consumption of high quantity of refined carbohydrate foods, particularly bread. These associations were apparently stronger in subjects with low vegetable consumption.

Determinants of Quality of Interview and Impact on Risk Estimates in a Case-Control Study of Bladder Cancer

PubMed Central

Silverman, Debra T.; Malats, Núria; Tardon, Adonina; Garcia-Closas, Reina; Serra, Consol; Carrato, Alfredo; Fortuny, Joan; Rothman, Nathaniel; Dosemeci, Mustafa; Kogevinas, Manolis

2009-01-01

The authors evaluated potential determinants of the quality of the interview in a case-control study of bladder cancer and assessed the effect of the interview quality on the risk estimates. The analysis included 1,219 incident bladder cancer cases and 1,271 controls recruited in Spain in 1998–2001. Information on etiologic factors for bladder cancer was collected through personal interviews, which were scored as unsatisfactory, questionable, reliable, or high quality by the interviewers. Eight percent of the interviews were unsatisfactory or questionable. Increasing age, lower socioeconomic status, and poorer self-perceived health led to higher proportions of questionable or unreliable interviews. The odds ratio for cigarette smoking, the main risk factor for bladder cancer, was 6.18 (95% confidence interval: 4.56, 8.39) overall, 3.20 (95% confidence interval: 1.13, 9.04) among unsatisfactory or questionable interviews, 6.86 (95% confidence interval: 4.80, 9.82) among reliable interviews, and 7.70 (95% confidence interval: 3.64, 16.30) among high-quality interviews. Similar trends were observed for employment in high-risk occupations, drinking water containing elevated levels of trihalomethanes, and use of analgesics. Higher quality interviews led to stronger associations compared with risk estimation that did not take the quality of interview into account. The collection of quality of interview scores and the exclusion of unreliable interviews probably reduce misclassification of exposure in observational studies. PMID:19478234

Comparison of Coregistration Accuracy of Pelvic Structures Between Sequential and Simultaneous Imaging During Hybrid PET/MRI in Patients with Bladder Cancer.

PubMed

Rosenkrantz, Andrew B; Balar, Arjun V; Huang, William C; Jackson, Kimberly; Friedman, Kent P

2015-08-01

The aim of this study was to compare coregistration of the bladder wall, bladder masses, and pelvic lymph nodes between sequential and simultaneous PET and MRI acquisitions obtained during hybrid (18)F-FDG PET/MRI performed using a diuresis protocol in bladder cancer patients. Six bladder cancer patients underwent (18)F-FDG hybrid PET/MRI, including IV Lasix administration and oral hydration, before imaging to achieve bladder clearance. Axial T2-weighted imaging (T2WI) was obtained approximately 40 minutes before PET ("sequential") and concurrently with PET ("simultaneous"). Three-dimensional spatial coordinates of the bladder wall, bladder masses, and pelvic lymph nodes were recorded for PET and T2WI. Distances between these locations on PET and T2WI sequences were computed and used to compare in-plane (x-y plane) and through-plane (z-axis) misregistration relative to PET between T2WI acquisitions. The bladder increased in volume between T2WI acquisitions (sequential, 176 [139] mL; simultaneous, 255 [146] mL). Four patients exhibited a bladder mass, all with increased activity (SUV, 9.5-38.4). Seven pelvic lymph nodes in 4 patients showed increased activity (SUV, 2.2-9.9). The bladder wall exhibited substantially less misregistration relative to PET for simultaneous, compared with sequential, acquisitions in in-plane (2.8 [3.1] mm vs 7.4 [9.1] mm) and through-plane (1.7 [2.2] mm vs 5.7 [9.6] mm) dimensions. Bladder masses exhibited slightly decreased misregistration for simultaneous, compared with sequential, acquisitions in in-plane (2.2 [1.4] mm vs 2.6 [1.9] mm) and through-plane (0.0 [0.0] mm vs 0.3 [0.8] mm) dimensions. FDG-avid lymph nodes exhibited slightly decreased in-plane misregistration (1.1 [0.8] mm vs 2.5 [0.6] mm), although identical through-plane misregistration (4.0 [1.9] mm vs 4.0 [2.8] mm). Using hybrid PET/MRI, simultaneous imaging substantially improved bladder wall coregistration and slightly improved coregistration of bladder masses and pelvic lymph nodes.

Gender Differences in Bladder Cancer Treatment Decision Making.

PubMed

Pozzar, Rachel A; Berry, Donna L

2017-03-01

To explore gender differences in bladder cancer treatment decision making.
. Secondary qualitative analysis of interview transcripts.
. One multidisciplinary genitourinary oncology clinic (Dana-Farber Cancer Institute) and two urology clinics (Brigham and Women's Hospital and Beth Israel Deaconess Medical Center) in Boston, MA.
. As part of the original study, 45 men and 15 women with bladder cancer participated in individual interviews. Participants were primarily Caucasian, and most had at least some college education.
. Word frequency reports were used to identify thematic differences between the men's and women's statements. Line-by-line coding of constructs prevalent among women was then performed on all participants in NVivo 9. Coding results were compared between genders using matrix coding queries.
. The role of family in the decision-making process was found to be a dominant theme for women but not for men. Women primarily described family members as facilitators of bladder cancer treatment-related decisions, but men were more likely to describe family in a nonsupportive role.
. The results suggest that influences on the decision-making process are different for men and women with bladder cancer. Family may play a particularly important role for women faced with bladder cancer treatment-related decisions.
. Clinical nurses who care for individuals with bladder cancer should routinely assess patients' support systems and desired level of family participation in decision making. For some people with bladder cancer, family may serve as a stressor. Nurses should support the decision-making processes of all patients and be familiar with resources that can provide support to patients who do not receive it from family.

About the Prostate and Urologic Cancer Research Group | Division of Cancer Prevention

Cancer.gov

The Prostate and Urologic Cancer Research Group conducts and supports research on prostate and bladder cancers, and new approaches to clinical prevention studies including cancer immunoprevention. The group develops, implements and monitors research efforts in chemoprevention, nutrition, genetic, and immunologic interventions, screening, early detection and other prevention

Antitumor killer lymphocytes in the peripheral blood of a patient with transitional cell carcinoma of the bladder.

PubMed

Kim, C J; Yuasa, T; Kushima, R; Tomoyoshi, T; Seto, A

1998-05-01

Peripheral blood lymphocytes (PBL) from patients with bladder cancer also contain cells possessing cytotoxic activity against autologous tumor cells. These cells are phenotypically heterogenous and include natural killer (NK) and cytotoxic T cells. This study investigated the role of cytotoxic lymphocytes directed against autologous bladder cancer cells. PBL were obtained at intervals before and after surgery and analyzed for cytotoxic activity against autologous bladder cancer cells in 4-hour 51Cr release assay. PBL stimulated with autologous tumor cells were also transformed with human T-lymphotropic virus type-1, establishing a cell line (KB31) which was analyzed for phenotype and cytotoxic activity against the autologous tumor cells. PBL preoperative cytotoxic activity was low, but increased after surgery. Cytotoxic activity was found not only against autologous bladder cancer cells, but also against heterologous bladder cancer (KK-47) and myeloid leukemia (K562) cells, with the highest activity against the heterologous cell lines. The cytotoxic activity of KB31 was 40% against autologous tumor cells 6 weeks after initiation of the cell line, but decreased to 5% by 6 months. This activity was lower than that against the other cell lines, and was similar to that of PBL in short-term culture. Fluorescence-activated cell sorter (FACS) analysis demonstrated that in KB31 cells at 6 weeks, CD8+ cells were dominant, but CD56+ cells predominated at 6 months. These results suggest that the presence of cytotoxic activity in the peripheral blood of the patient was due to both cytotoxic T cells and NK cells. The cytotoxic activity was lowest prior to surgery and increased postoperatively.

Unusual Cancers of Childhood Treatment (PDQ®)—Health Professional Version

Cancer.gov

Very rare cancers in children include nasopharyngeal, thyroid, oral, salivary, laryngeal, breast, lung, esophageal, cardiac, adrenocortical, gastric, pancreatic, GIST, carcinoid tumors, colorectal, bladder, and skin cancer. Get information about the diagnosis and treatment of these unusual childhood cancers in this summary for clinicians.

Steroid receptor coactivator-3 regulates glucose metabolism in bladder cancer cells through coactivation of hypoxia inducible factor 1α.

PubMed

Zhao, Wei; Chang, Cunjie; Cui, Yangyan; Zhao, Xiaozhi; Yang, Jun; Shen, Lan; Zhou, Ji; Hou, Zhibo; Zhang, Zhen; Ye, Changxiao; Hasenmayer, Donald; Perkins, Robert; Huang, Xiaojing; Yao, Xin; Yu, Like; Huang, Ruimin; Zhang, Dianzheng; Guo, Hongqian; Yan, Jun

2014-04-18

Cancer cell proliferation is a metabolically demanding process, requiring high glycolysis, which is known as "Warburg effect," to support anabolic growth. Steroid receptor coactivator-3 (SRC-3), a steroid receptor coactivator, is overexpressed and/or amplified in multiple cancer types, including non-steroid targeted cancers, such as urinary bladder cancer (UBC). However, whether SRC-3 regulates the metabolic reprogramming for cancer cell growth is unknown. Here, we reported that overexpression of SRC-3 accelerated UBC cell growth, accompanied by the increased expression of genes involved in glycolysis. Knockdown of SRC-3 reduced the UBC cell glycolytic rate under hypoxia, decreased tumor growth in nude mice, with reduction of proliferating cell nuclear antigen and lactate dehydrogenase expression levels. We further revealed that SRC-3 could interact with hypoxia inducible factor 1α (HIF1α), which is a key transcription factor required for glycolysis, and coactivate its transcriptional activity. SRC-3 was recruited to the promoters of HIF1α-target genes, such as glut1 and pgk1. The positive correlation of expression levels between SRC-3 and Glut1 proteins was demonstrated in human UBC patient samples. Inhibition of glycolysis through targeting HK2 or LDHA decelerated SRC-3 overexpression-induced cell growth. In summary, overexpression of SRC-3 promoted glycolysis in bladder cancer cells through HIF1α to facilitate tumorigenesis, which may be an intriguing drug target for bladder cancer therapy.

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

NASA Astrophysics Data System (ADS)

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.

Decitabine in Treating Patients With Advanced Solid Tumors

ClinicalTrials.gov

2013-02-06

Male Breast Cancer; Recurrent Bladder Cancer; Recurrent Breast Cancer; Recurrent Melanoma; Stage III Melanoma; Stage IV Bladder Cancer; Stage IV Breast Cancer; Stage IV Melanoma; Unspecified Adult Solid Tumor, Protocol Specific

LINC00857 expression predicts and mediates the response to platinum-based chemotherapy in muscle-invasive bladder cancer.

PubMed

Dudek, Aleksandra M; van Kampen, Jasmijn G M; Witjes, J Alfred; Kiemeney, Lambertus A L M; Verhaegh, Gerald W

2018-06-01

Approximately 20% of patients with bladder cancer are diagnosed with muscle-invasive disease (MIBC). The treatment involves radical cystectomy, but almost 50% of patients with MIBC eventually relapse and develop metastasis. The use of platinum-based chemotherapy in the neoadjuvant setting or for metastatic patients has been shown to improve the overall survival in a subset of patients. Unfortunately, no biomarkers are available to select patients with MIBC who will benefit from chemotherapy or to monitor the efficacy of the treatment. Recently, long noncoding RNAs (lncRNAs) were shown to regulate a variety of processes involved in the development and progression of cancer, including bladder cancer. Moreover, several lncRNAs have been shown to play a role in chemotherapy resistance. Here, we analyzed lncRNA expression associated with response to platinum-based chemotherapy in metastatic MIBC using data from the MiTranscriptome lncRNA expression database. Expression of the lncRNA, LINC00857, was found to be upregulated in tumors from patients that did not respond to platinum-based chemotherapy. Moreover, high expression of LINC00857 is correlated with shorter recurrence-free and overall survival of patients with MIBC. Knockdown of LINC00857 significantly decreased cell viability of bladder cancer cell lines through the induction of apoptosis. Furthermore, LINC00857 knockdown sensitized UM-UC-3 and T24 bladder cancer cells to cisplatin, via the negative regulation of the LMAN1 gene. Our data indicate that LINC00857 plays an important role in the regulation of response to platinum-based chemotherapy. LINC00857 potentially could serve as a novel prognostic and predictive biomarker and might be a therapeutic target to overcome cisplatin resistance in patients with MIBC. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Relevance of prostate cancer in patients with synchronous invasive bladder urothelial carcinoma: a monocentric retrospective analysis.

PubMed

Dell'Atti, Lucio

2015-03-31

We retrospectively reviewed data of patients with incidental prostate cancer (PCa) who underwent radical cystoprostatectomy (RCP) for invasive bladder cancer and we analyzed their features with regard to incidence, pathologic characteristics, clinical significance, and implications for management. Clinical data and pathological features of 64 patients who underwent standard RCP for bladder cancer were included in this study. Besides the urothelial carcinoma of the urinary bladder, the location and tumor volume of the PCa, prostate apex involvement, Gleason score, pathological staging and surgical margins were evaluated. Clinically significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, stage ≥ pT3, lymph node involvement, positive surgical margin or multifocality of three or more lesions. Postoperative follow-up was scheduled every 3 months in the first year, every 6 months in the second and third year, annually thereafter. 11 out of 64 patients (17.2%) who underwent RCP had incidentally diagnosed PCa. 3 cases (27.3%) were diagnosed as significant PCa, while 8 cases (72.7%) were clinically insignificant. The positive surgical margin of PCa was detected in 1 patient with significant disease. The prostate apex involvement was present in 1 patient of the significant PCa group. Median follow-up period was 47.8 ± 29.2 (range 4-79). During the follow-up, biochemical recurrence occurred in 1 patient (9%). Concerning the cancer specific survival there was no statistical significance (P = 0.326) between the clinically significant and clinical insignificant cancer group. In line with published studies, incidental PCa does not impact on the prognosis of bladder cancer of patients undergoing RCP.

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

PubMed Central

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) I2 = 0%, eight studies for fruits and vegetables, 0.97 (95% CI: 0.94–1.00, I2 = 10%, 10 studies) for vegetables and 0.98 (95% CI: 0.96–1.00, I2 = 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, I2 = 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. PMID:25461441

History of Non-Muscle-Invasive Bladder Cancer May Have a Worse Prognostic Impact in cT2-4aN0M0 Bladder Cancer Patients Treated With Radical Cystectomy.

PubMed

Kayama, Emina; Kikuchi, Eiji; Fukumoto, Keishiro; Shirotake, Suguru; Miyazaki, Yasumasa; Hakozaki, Kyohei; Kaneko, Gou; Yoshimine, Shunsuke; Tanaka, Nobuyuki; Takahiro, Maeda; Kanai, Kunimitsu; Oyama, Masafumi; Nakajima, Yosuke; Hara, Satoshi; Monma, Tetsuo; Oya, Mototsugu

2018-04-28

To investigate whether a history of non-muscle-invasive bladder cancer (NMIBC) plays a prognostic role in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy in the era when neoadjuvant chemotherapy was established as standard therapy for MIBC. A total of 282 patients who were diagnosed with cT2-T4aN0M0 bladder cancer treated with open radical cystectomy at our institutions were included. Initially diagnosed MIBC without a history of NMIBC was defined as primary MIBC group (n = 231), and MIBC that progressed from NMIBC was defined as progressive MIBC (n = 51). The rate of cT3/4a tumors was significantly higher in the primary MIBC group than in the progressive MIBC group (P = .004). Five-year recurrence-free survival and cancer-specific survival (CSS) rates for the primary MIBC group versus progressive MIBC group were 68.2% versus 55.9% (P = .039) and 76.1% versus 61.6% (P = .005), respectively. Progressive MIBC (hazard ratio, 2.170; P = .008) was independently associated with cancer death. In the primary MIBC group, the 5-year CSS rate in patients treated with neoadjuvant chemotherapy was 85.4%, which was significantly higher than that in patients without (71.5%, P = .023). In the progressive MIBC group, no significant differences were observed in CSS between patients treated with and without neoadjuvant chemotherapy. MIBC that progressed from NMIBC had a significantly worse clinical outcome than MIBC without a history of NMIBC and may not respond as well to neoadjuvant chemotherapy. These results are informative, even for NMIBC patients treated with conservative intravesical therapy. Copyright © 2018 Elsevier Inc. All rights reserved.

Incidence and Mortality of Bladder Cancer and their Relationship with Development in Asia.

PubMed

Pakzad, Reza; Mohammadian-Hafshejani, Abdollah; Mohammadian, Mahdi; Pakzad, Iraj; Safiri, Saeid; Khazaei, Salman; Salehiniya, Hamid

2015-01-01

Over the past decade, bladder cancer was associated with a significant increase. Given the importance of the impact of socioeconomic status on the distribution of cancer incidence and mortality, and the need to information on these parameters for prevention planning, the aim of this study was to evaluate data for bladder cancer and their relationship with human development index (HDI) and its components in Asia in 2012. The study was conducted based on data from the world data of cancer and the World Bank (including the HDI and its components). The incidence and mortality rates were drawn for Asian countries. To analyze data, correlation tests between incidence and death rates, and HDI and its components were employed with a significance level of 0.05 using SPSS software. A total incidence of 696,231 cases (68.7% in males and 31.3% in females, sex ratio of 2.19:1) and 524,465 deaths (67.0% in men and 32.9% in women, sex ratio was 2.03:1) were recorded in Asian countries in 2012. Correlation between HDI and standardized incidence rate was 0.241 overall (p=0.106), 0.236 in men (p=0.114) and -0.250 in women (p=0.094). Also between HDI and standardized mortality rate 0.025 (p=0.871) in men 0.118 (p=0.903) and in women 0.014 (p=0.927). Bladder cancer incidence is higher in developed countries, but the rate is declining, and in less developed and developing countries it is growing. There was no statistically significant correlation between the standardized incidence rate of bladder cancer and the HDI and its dimensions in Asia, except for the level of education.

Gemcitabine Hydrochloride and Eribulin Mesylate in Treating Patients With Bladder Cancer That is Advanced or Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-05-23

Metastatic Ureteral Neoplasm; Metastatic Urethral Neoplasm; Stage III Bladder Urothelial Carcinoma AJCC v6 and v7; Stage III Ureter Cancer AJCC v7; Stage III Urethral Cancer AJCC v7; Stage IV Bladder Urothelial Carcinoma AJCC v7; Stage IV Ureter Cancer AJCC v7; Stage IV Urethral Cancer AJCC v7; Ureter Urothelial Carcinoma; Urethral Urothelial Carcinoma

Cancer incidence in adults living in the vicinity of nuclear power plants in France, based on data from the French Network of Cancer Registries.

PubMed

Desbiolles, Alice; Roudier, Candice; Goria, Sarah; Stempfelet, Morgane; Kairo, Cécile; Quintin, Cécile; Bidondo, Marie-Laure; Monnereau, Alain; Vacquier, Blandine

2018-03-01

Nuclear power plants (NPPs) release toxic emissions into the environment that may affect neighboring populations. This ecologic study was designed to investigate the possibility of an excess incidence of cancer in the vicinity of French NPPs by examining the incidence by municipality of 12 types of cancer in the population aged 15 years and older during the 1995-2011 period. Population exposure to pollution was estimated on the basis of distance from towns of residence to the NPP. Using regression models, we assessed the risk of cancer in a 20-km zone around NPPs and observed an excess incidence of bladder cancer (Relative Risk (RR), 95% Credibility Interval (95% CI)) in men and women (RR men  = 1.08; 95% CI: 1.00, 1.17 and RR women  = 1.19; 95% CI: 1.02, 1.39). Women living within the 20-km proximity areas had a significantly reduced risk of thyroid cancer (RR women  = 0.86; 95% CI: 0.77, 0.96). No excess risk of hematologic malignancies in either sex was seen. The higher than expected incidence of bladder cancer may be due to an excess incidence localized around the Flamanville NPP and the nearby La Hague nuclear waste treatment center, which is a source of chemical contaminants, many (including arsenic) of them known risk factors for bladder cancer. Differences in medical practices could explain the reduced risk of thyroid cancer. In this first study of adults living near NPPs in France, cancer incidence is significantly higher than in the references populations for one of the cancer types studied: bladder cancer. © 2017 UICC.

Deep Sequencing of Urinary RNAs for Bladder Cancer Molecular Diagnostics.

PubMed

Sin, Mandy L Y; Mach, Kathleen E; Sinha, Rahul; Wu, Fan; Trivedi, Dharati R; Altobelli, Emanuela; Jensen, Kristin C; Sahoo, Debashis; Lu, Ying; Liao, Joseph C

2017-07-15

Purpose: The majority of bladder cancer patients present with localized disease and are managed by transurethral resection. However, the high rate of recurrence necessitates lifetime cystoscopic surveillance. Developing a sensitive and specific urine-based test would significantly improve bladder cancer screening, detection, and surveillance. Experimental Design: RNA-seq was used for biomarker discovery to directly assess the gene expression profile of exfoliated urothelial cells in urine derived from bladder cancer patients ( n = 13) and controls ( n = 10). Eight bladder cancer specific and 3 reference genes identified by RNA-seq were quantitated by qPCR in a training cohort of 102 urine samples. A diagnostic model based on the training cohort was constructed using multiple logistic regression. The model was further validated in an independent cohort of 101 urines. Results: A total of 418 genes were found to be differentially expressed between bladder cancer and controls. Validation of a subset of these genes was used to construct an equation for computing a probability of bladder cancer score (P BC ) based on expression of three markers ( ROBO1, WNT5A , and CDC42BPB ). Setting P BC = 0.45 as the cutoff for a positive test, urine testing using the three-marker panel had overall 88% sensitivity and 92% specificity in the training cohort. The accuracy of the three-marker panel in the independent validation cohort yielded an AUC of 0.87 and overall 83% sensitivity and 89% specificity. Conclusions: Urine-based molecular diagnostics using this three-marker signature could provide a valuable adjunct to cystoscopy and may lead to a reduction of unnecessary procedures for bladder cancer diagnosis. Clin Cancer Res; 23(14); 3700-10. ©2017 AACR . ©2017 American Association for Cancer Research.

Vasculogenic mimicry in bladder cancer and its association with the aberrant expression of ZEB1

PubMed Central

Li, Baimou; Mao, Xiaopeng; Wang, Hua; Su, Guanyu; Mo, Chengqiang; Cao, Kaiyuan; Qiu, Shaopeng

2018-01-01

The aim of the present study was to investigate the associations between vasculogenic mimicry (VM) and zinc finger E-box binding homeobox 1 (ZEB1) in bladder cancer. VM structure and ZEB1 expression were analyzed by cluster of differentiation 34/periodic acid Schiff (PAS) double staining and immunohistochemical staining in 135 specimens from patients with bladder cancer, and a further 12 specimens from normal bladder tissues. Three-dimensional (3-D) culture was used to detect VM formation in the bladder transitional cancer cell lines UM-UC-3 and J82, and the immortalized human bladder epithelium cell line SV-HUC-1 in vitro. ZEB1 expression in these cell lines was compared by reverse transcription-quantitative polymerase chain reaction and western blot assays. In addition, small interfering RNA was used to inhibit ZEB1 in UM-UC-3 and J82 cells, followed by 3-D culturing of treated cell lines. As a result, VM was observed in 31.1% of specimens from bladder cancer tissues, and cases with high ZEB1 expression accounted for 60.0% of patients with bladder cancer. In addition, ZEB1 expression was closely associated with VM (r=0.189; P<0.05), and also increased as the grade and stage of the tumor developed. In an in vitro assay, UM-UC-3 and J82 cells exhibited VM formation, however, SV-HUC-1 did not. Furthermore, VM-forming cancer cell lines UM-UC-3 and J82 exhibited higher ZEB1 expression. Notably, VM formation was inhibited following knockdown of ZEB1. In conclusion, ZEB1 may be associated with VM in bladder cancer and serve an important role in the process of VM formation. However, its detailed mechanism requires further study. PMID:29552157

A meta-analysis of tea consumption and the risk of bladder cancer.

PubMed

Wang, Xiao; Lin, Yi-Wei; Wang, Shuai; Wu, Jian; Mao, Qi-Qi; Zheng, Xiang-Yi; Xie, Li-Ping

2013-01-01

Previous studies on the association between tea consumption and bladder cancer risk have only illustrated contradictory results. The role of tea in bladder carcinogenesis still remains conflicting. In order to illustrate the potential relationship between tea consumption and bladder cancer, a meta-analysis of case-control and cohort studies was conducted. Eligible studies were retrieved via both computerized searches and review of references. Stratified analyses on types of tea, gender, study design, ethnicity and smoking status were performed. Fixed- or random-effect models were used to summarize the estimates of OR with 95% CIs. Seventeen studies were eligible for our analysis. No statistical significance was detected between tea consumption and bladder cancer risk when comparing the highest with the lowest intake of tea (OR = 0.825, 95% CI 0.652-1.043). In the subgroup of green tea, we observed it illustrated a protective effect on bladder cancer (OR = 0.814, 95% CI 0.678-0.976). Our analysis indicated that green tea may have a protective effect on bladder cancer in Asian people. Further studies need to be conducted to better clarify the biological mechanisms. Copyright © 2012 S. Karger AG, Basel.

New clinical trial open for patients with muscle-invasive bladder cancer | Center for Cancer Research

Cancer.gov

Muscle-invasive bladder cancer is an aggressive form of bladder cancer in which the tumor invades deep into the musculature of the bladder wall, making it more likely to spread to other parts of the body. Standard treatment involves cisplatin-based chemotherapy followed by radical cystectomy, which is surgery to remove the bladder and nearby organs. However, many patients don’t receive chemotherapy before surgery or may not respond to it. Other patients are ineligible for cisplatin treatment due to poor kidney function. CCR investigators are leading a phase III trial to determine whether an immunotherapy drug given shortly after cystectomy can help these patients. Read more…

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

EPA Science Inventory

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...

Metastatic signet-ring cell cancer of the bladder responding to chemotherapy with capecitabine: case report and review of literature

PubMed Central

Michels, Jorg; Barbour, Sean; Cavers, Douglas; Chi, Kim N.

2010-01-01

Signet-ring cell cancers deriving from the bladder are rare entities and usually present with advanced incurable disease and associated poor outlook. No standard effective chemotherapeutic option has been described largely due to the rarity of this malignancy. We report a case of a patient with metastatic bladder cancer, signet-ring cell variant. The patient progressed rapidly on standard first-line bladder cancer chemotherapy with gemcitabine and carboplatin. He responded well to second-line capecitabine with a clinically meaningful progression-free survival. PMID:20368884

Occupational risk of bladder cancer among Iranian male workers

PubMed Central

Aminian, Omid; Saburi, Amin; Mohseni, Hossein; Akbari, Hamed; Chavoshi, Farzaneh; Akbari, Hesam

2014-01-01

Background: Approximately 5-10% of human cancers are thought to be caused by occupational exposure to carcinogens. Compare to other cancers, bladder cancer is most strongly linked to occupational exposure to chemical toxins. This study has been performed to understand which occupations and exposures are related to bladder cancer in Iran. Materials and Methods: This study is a case-control study which is conducted on cases with bladder cancer (160 cases) diagnosed in Baharlou hospital in 2007-2009. One hundred sixty cases without any occupational exposure were considered as controls matched for demographic characteristics. Demographic data and characteristics of occupation were compared. Results: Mean age of cases and controls were 63.7 and 64 years, respectively (P = 0.841). History of urinary tract stone had significantly difference in two groups (P = 0.039). Occupations such as bus and truck driving, road and asphalt making, mechanics, working in refinery and Petrochemical, plastic, metal manufactory, welding, and pipeline founded a higher risk for bladder cancer rather than controls. Conclusion: Our findings on Iranian workers are concurrent and compatible with findings of previous reports about occupational and environmental risk factors of bladder cancer. Although our study population was PMID:24833825

Monitoring of permeability of different analytes in human normal and cancerous bladder tissues in vitro using optical coherence tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bingsong Lei; Xiaoyuan Deng; Huajiang Wei

2014-12-31

We report our preliminary results on quantification of glucose and dimethyl sulfoxide (DMSO) diffusion in normal and cancerous human bladder tissues in vitro by using a spectral domain optical coherence tomography (SD-OCT). The permeability coefficients (PCs) of a 30% aqueous solution of glucose are found to be (7.92 ± 0.81) × 10{sup -6} cm s{sup -1} and (1.19 ± 0.13) × 10{sup -5} cm s{sup -1} in normal and cancerous bladder tissues, respectively. The PCs of 50% DMSO are calculated to be (8.99 ± 0.93) × 10{sup -6} cm s{sup -1} and (1.43 ± 0.17) × 10{sup -5} cm s{supmore » -1} in normal and cancerous bladder tissues, respectively. The obtained results show a statistically significant difference in permeability of normal and cancerous tissue and indicate that the PC of 50% DMSO is about 1.13-and 1.21-fold higher than that of 30% glucose in normal bladder and cancerous bladder tissues, respectively. Thus, the quantitative measurements with the help of PCs from OCT images can be a potentially powerful method for bladder cancer detection. (optical coherence tomography)« less

G-protein-coupled receptor 137 accelerates proliferation of urinary bladder cancer cells in vitro.

PubMed

Du, Yiheng; Bi, Wenhuan; Zhang, Fei; Wu, Wenbo; Xia, Shujie; Liu, Haitao

2015-01-01

Urinary bladder cancer is a worldwide concern because of its level of incidence and recurrence. To search an effective therapeutic strategy for urinary bladder cancer, it is important to identify proteins involved in tumorigenesis that could serve as potential targets for diagnosis and treatment. G-protein-coupled receptors (GPRs) constitute a large protein family of receptors that sense molecules outside the cell and activate signal transduction pathways and cellular responses inside the cell. GPR137 is a newly discovered human gene encoding orphan GPRs. In this study, we aimed to investigate the physiological role of GPR137 in urinary bladder cancer. The effect of GPR137 on cell growth was examined via an RNA interference (RNAi) lentivirus system in two human urinary bladder cancer cell lines BT5637 and T24. Lentivirus-mediated RNAi could specifically suppressed GPR137 expression in vitro, resulting in alleviated cell viability and impaired colony formation, as well as blocks G0/G1 and S phases of the cell cycle. These results suggested GPR137 as an essential player in urinary bladder cancer cell growth, and it may serve as a potential target for gene therapy in the treatment of urinary bladder cancer. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

An integrated double-filtration microfluidic device for isolation, enrichment and quantification of urinary extracellular vesicles for detection of bladder cancer

PubMed Central

Liang, Li-Guo; Kong, Meng-Qi; Zhou, Sherry; Sheng, Ye-Feng; Wang, Ping; Yu, Tao; Inci, Fatih; Kuo, Winston Patrick; Li, Lan-Juan; Demirci, Utkan; Wang, ShuQi

2017-01-01

Extracellular vesicles (EVs), including exosomes and microvesicles, are present in a variety of bodily fluids, and the concentration of these sub-cellular vesicles and their associated biomarkers (proteins, nucleic acids, and lipids) can be used to aid clinical diagnosis. Although ultracentrifugation is commonly used for isolation of EVs, it is highly time-consuming, labor-intensive and instrument-dependent for both research laboratories and clinical settings. Here, we developed an integrated double-filtration microfluidic device that isolated and enriched EVs with a size range of 30–200 nm from urine, and subsequently quantified the EVs via a microchip ELISA. Our results showed that the concentration of urinary EVs was significantly elevated in bladder cancer patients (n = 16) compared to healthy controls (n = 8). Receiver operating characteristic (ROC) analysis demonstrated that this integrated EV double-filtration device had a sensitivity of 81.3% at a specificity of 90% (16 bladder cancer patients and 8 healthy controls). Thus, this integrated device has great potential to be used in conjunction with urine cytology and cystoscopy to improve clinical diagnosis of bladder cancer in clinics and at point-of-care (POC) settings. PMID:28436447

Collecting and Studying Blood and Tissue Samples From Patients With Locally Recurrent or Metastatic Prostate or Bladder/Urothelial Cancer

ClinicalTrials.gov

2017-12-04

Healthy Control; Localized Urothelial Carcinoma of the Renal Pelvis and Ureter; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Prostate Cancer

Arsenic in drinking water and urinary tract cancers: a systematic review of 30 years of epidemiological evidence.

PubMed

Saint-Jacques, Nathalie; Parker, Louise; Brown, Patrick; Dummer, Trevor Jb

2014-06-02

Arsenic in drinking water is a public health issue affecting hundreds of millions of people worldwide. This review summarizes 30 years of epidemiological studies on arsenic exposure in drinking water and the risk of bladder or kidney cancer, quantifying these risks using a meta-analytical framework. Forty studies met the selection criteria. Seventeen provided point estimates of arsenic concentrations in drinking water and were used in a meta-analysis of bladder cancer incidence (7 studies) and mortality (10 studies) and kidney cancer mortality (2 studies). Risk estimates for incidence and mortality were analyzed separately using Generalized Linear Models. Predicted risks for bladder cancer incidence were estimated at 10, 50 and 150 μg/L arsenic in drinking water. Bootstrap randomizations were used to assess robustness of effect size. Twenty-eight studies observed an association between arsenic in drinking water and bladder cancer. Ten studies showed an association with kidney cancer, although of lower magnitude than that for bladder cancer. The meta-analyses showed the predicted risks for bladder cancer incidence were 2.7 [1.2-4.1]; 4.2 [2.1-6.3] and; 5.8 [2.9-8.7] for drinking water arsenic levels of 10, 50, and 150 μg/L, respectively. Bootstrapped randomizations confirmed this increased risk, but, lowering the effect size to 1.4 [0.35-4.0], 2.3 [0.59-6.4], and 3.1 [0.80-8.9]. The latter suggests that with exposures to 50 μg/L, there was an 83% probability for elevated incidence of bladder cancer; and a 74% probability for elevated mortality. For both bladder and kidney cancers, mortality rates at 150 ug/L were about 30% greater than those at 10 μg/L. Arsenic in drinking water is associated with an increased risk of bladder and kidney cancers, although at lower levels (<150 μg/L), there is uncertainty due to the increased likelihood of exposure misclassification at the lower end of the exposure curve. Meta-analyses suggest exposure to 10 μg/L of arsenic in drinking water may double the risk of bladder cancer, or at the very least, increase it by about 40%. With the large number of people exposed to these arsenic concentrations worldwide the public health consequences of arsenic in drinking water are substantial.

NOTCH pathway inactivation promotes bladder cancer progression

PubMed Central

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

2015-01-01

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. PMID:25574842

An adaptive radiotherapy planning strategy for bladder cancer using deformation vector fields.

PubMed

Vestergaard, Anne; Kallehauge, Jesper Folsted; Petersen, Jørgen Breede Baltzer; Høyer, Morten; Søndergaard, Jimmi; Muren, Ludvig Paul

2014-09-01

Adaptive radiotherapy (ART) has considerable potential in treatment of bladder cancer due to large inter-fractional changes in shape and size of the target. The aim of this study was to compare our clinically applied method for plan library creation that involves manual bladder delineations (Clin-ART) with a method using the deformation vector fields (DVFs) resulting from intensity-based deformable image registrations (DVF-based ART). The study included thirteen patients with urinary bladder cancer who had daily cone beam CTs (CBCTs) acquired for set-up. In both ART strategies investigated, three plan selection volumes were generated using the CBCTs from the first four fractions; in Clin-ART boolean combinations of delineated bladders were used, while the DVF-based strategy applied combinations of the mean and standard deviation of patient-specific DVFs. The volume ratios (VRs) of the course-averaged PTV for the two ART strategies relative the non-adaptive PTV were calculated. Both Clin-ART and DVF-based ART considerably reduced the course-averaged PTV, compared to non-adaptive RT. The VR for DVF-based ART was lower than for Clin-ART (0.65 vs. 0.73; p<0.01). DVF-based ART for bladder irradiation has a considerable normal tissue sparing potential surpassing our already highly conformal clinically applied ART strategy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Recombinant Mycobacterium bovis BCG for immunotherapy in nonmuscle invasive bladder cancer.

PubMed

Begnini, K R; Buss, J H; Collares, T; Seixas, F K

2015-05-01

In the past three decades, intravesical instillation of Mycobacterium bovis bacille Calmette-Guérin (BCG) has been used for treating bladder cancer and it still remains at the forefront of immunotherapy for cancer patients. Although BCG-based therapy is the most effective intravesical therapy for this kind of tumor and represents the only agent known to reduce progression into muscle invasive bladder cancer, BCG is ineffective in approximately 30-40 % of cases and disease recurs in up to 50 % of patients. Since that BCG is considered an effective vehicle for delivery of antigens due to its unique characteristics, the genetic manipulation of these mycobacteria has been appealing in the search for less toxic and more potent therapeutic agents for bladder cancer immunotherapy. Herein, we discuss current advances in recombinant BCG construction, research, concerns, and future directions to promote the development of this promising immunotherapeutic approach for bladder cancer.

The association of lifetime physical inactivity with bladder and renal cancer risk: A hospital-based case-control analysis.

PubMed

Cannioto, Rikki; Etter, John Lewis; Guterman, Lauren Beryl; Joseph, Janine M; Gulati, Nicholas R; Schmitt, Kristina L; LaMonte, Michael J; Nagy, Ryan; Minlikeeva, Albina; Szender, James Brian; Moysich, Kirsten B

2017-08-01

Recreational physical inactivity has been gaining recognition as an independent epidemiological exposure of interest in relation to cancer endpoints due to evidence suggesting that it may associate with cancer independent of obesity. In the current analyses, we examined the associations of lifetime recreational physical inactivity with renal and bladder cancer risk. In this hospital-based case-control study, we identified N=160 renal cancer patients, N=208 bladder cancer patients, and N=766 age frequency-matched controls without cancer. Participants self-reporting never participating in any regular/weekly recreational physical activity throughout their lifetime were classified as physically inactive. Utilizing unconditional multivariable logistic regression analyses, we estimated odds ratios and 95% confidence intervals to represent the associations between lifetime physical inactivity and renal and bladder cancer risk. In multivariable logistic regression models, we observed significant positive associations between lifetime recreational physical inactivity and renal cancer and bladder cancer risk: odds ratio=1.77 (95% CI: 1.10-2.85) and odds ratio=1.73 (95% CI: 1.13-2.63), respectively. Similar associations also persisted among individuals who were not obese for both renal and bladder cancer: odds ratio=1.75 (95% CI: 1.03-2.98) and odds ratio=1.70 (95% CI: 1.08-2.69), respectively. In this case-control study, we observed evidence of a positive association between renal and bladder cancer with lifetime recreational physical inactivity. These data add to the growing body of evidence suggesting that physical inactivity may be an important independent risk factor for cancer. However, additional studies using a larger sample and prospectively collected data are needed to substantiate the current findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Activity of Class I-IV Alcohol Dehydrogenase Isoenzymes and Aldehyde Dehydrogenase in Bladder Cancer Cells.

PubMed

Orywal, Karolina; Jelski, Wojciech; Werel, Tadeusz; Szmitkowski, Maciej

2018-01-02

The aim of this study was to determine the differences in the activity of Alcohol Dehydrogenase (ADH) isoenzymes and Aldehyde Dehydrogenase (ALDH) in normal and cancerous bladder cells. Class III, IV of ADH and total ADH activity were measured by the photometric method and class I, II ADH and ALDH activity by the fluorometric method. Significantly higher total activity of ADH was found in both, low-grade and high-grade bladder cancer, in comparison to healthy tissues. The increased activity of total ADH in bladder cancer cells may be the cause of metabolic disorders in cancer cells, which may intensify carcinogenesis.

Cancer among farmers in central Italy.

PubMed

Forastiere, F; Quercia, A; Miceli, M; Settimi, L; Terenzoni, B; Rapiti, E; Faustini, A; Borgia, P; Cavariani, F; Perucci, C A

1993-12-01

This case-referent study evaluated cancer risks among farmers in central Italy. Cancer cases (N = 1674, 17 sites) were selected from all deceased men aged 35-80 years; a random sample of 480 decedents formed the reference series. Farmers had a decreased risk of lung and bladder cancer and melanoma and nonsignificant excess risks for stomach, rectal, kidney, and nonmelanoma skin cancer. Stomach and kidney cancer were significantly increased among the farmers with > 10 years' experience, and stomach, rectal, and pancreatic cancer were increased among licensed pesticide users with > 10 years' experience. Possible relationships emerged between specific crops and cancer: fruit and colon and bladder cancer, wheat and prostate cancer, olives and kidney cancer, and potato and kidney cancer. The results regarding stomach, pancreatic, lung, bladder, and prostate cancer and melanoma congrue with earlier results. The kidney cancer excess, the association of colon and bladder cancer with orchard farming, and the excess of rectal cancer among licensed farmers are new and unexpected findings.

Androgen receptor activation: a prospective therapeutic target for bladder cancer?

PubMed

Mizushima, Taichi; Tirador, Kathleen A; Miyamoto, Hiroshi

2017-03-01

Patients with non-muscle-invasive or muscle-invasive bladder cancer undergoing surgery and currently available conventional therapy remain having a high risk of tumor recurrence or progression, respectively. Novel targeted molecular therapy is therefore expected to improve patient outcomes. Meanwhile, substantially higher incidence of bladder cancer in men has prompted research on androgen-mediated androgen receptor (AR) signaling in this malignancy. Indeed, preclinical evidence has suggested that AR signaling plays an important role in urothelial carcinogenesis and tumor outgrowth as well as resistance to some of the currently available conventional non-surgical therapies. Areas covered: We summarize and discuss available data suggesting the involvement of AR and its potential downstream targets in the development and progression of bladder cancer. Associations between AR signaling and sensitivity to cisplatin/doxorubicin or bacillus Calmette-Guérin treatment are also reviewed. Expert opinion: AR activation is likely to correlate with the promotion of urothelial carcinogenesis and cancer outgrowth as well as resistance to conventional therapies. Molecular therapy targeting the AR may thus provide effective chemopreventive and therapeutic approaches for urothelial cancer. Accordingly, bladder cancer can now be considered as an endocrine-related neoplasm. Clinical application of various anti-AR therapies available for AR-dependent prostate cancer to bladder cancer patients is anticipated.

Meat intake and bladder cancer risk in a Swedish prospective cohort.

PubMed

Larsson, Susanna C; Johansson, Jan-Erik; Andersson, Swen-Olof; Wolk, Alicja

2009-02-01

High meat consumption could potentially increase the risk of bladder cancer, but findings from epidemiologic studies are inconsistent. We prospectively examined the association between meat intake and bladder cancer risk in a population-based cohort study. We prospectively followed 82,002 Swedish women and men who were free from cancer and completed a food-frequency questionnaire in 1997. Incident cases of bladder cancer were identified in the Swedish cancer registries. Cox proportional hazards models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, smoking status, pack-years of smoking, and total energy intake. During a mean follow-up of 9.4 years, 485 incident cases of bladder cancer (76 women and 409 men) were ascertained in the cohort. We observed no association between the intake of total or any specific type of meat and the risk of bladder cancer. The multivariate HRs (95% CIs) comparing the highest and the lowest category of intake were 1.05 (0.71-1.55) for total meat, 1.00 (0.71-1.41) for red meat, 1.01 (0.80-1.28) for processed meats, 0.96 (0.70-1.30) for chicken/poultry, and 0.92 (0.65-1.30) for fried meats/fish. The associations did not vary by sex or smoking status. These results do not support the hypothesis that intake of red meat, processed meat, poultry, or fried meats/fish is associated with the risk of developing bladder cancer.

Does increased urination frequency protect against bladder cancer?

PubMed

Silverman, Debra T; Alguacil, Juan; Rothman, Nathaniel; Real, Francisco X; Garcia-Closas, Montserrat; Cantor, Kenneth P; Malats, Nuria; Tardon, Adonina; Serra, Consol; Garcia-Closas, Reina; Carrato, Alfredo; Lloreta, Josep; Samanic, Claudine; Dosemeci, Mustafa; Kogevinas, Manolis

2008-10-01

Experimental studies suggest that increased urination frequency may reduce bladder cancer risk if carcinogens are present in the urine. Only 2 small studies of the effect of increased urination frequency on bladder cancer risk in humans have been conducted with conflicting results. Our purpose was to evaluate the effect of urination frequency on risk of bladder cancer in a large, multicenter case-control study. We analyzed data based on interviews conducted with 884 patients with newly diagnosed, bladder cancer and 996 controls from 1998 to 2001 in Spain. We observed a consistent, inverse trend in risk with increasing nighttime voiding frequency in both men (p = 0.0003) and women (p = 0.07); voiding at least 2 times per night was associated with a significant, 40-50% risk reduction. The protective effect of nocturia was apparent among study participants with low, moderate and high water consumption. The risk associated with cigarette smoking was reduced by nocturia. Compared with nonsmokers who did not urinate at night, current smokers who did not urinate at night had an OR of 7.0 (95% CI = 4.7-10.2), whereas those who voided at least twice per night had an OR of 3.3 (95% CI = 1.9-5.8) (p value for trend = 0.0005). Our findings suggest a strong protective effect of nocturia on bladder cancer risk, providing evidence in humans that bladder cancer risk is related to the contact time of the urothelium with carcinogens in urine. Increased urination frequency, coupled with possible dilution of the urine from increased water intake, may diminish the effect of urinary carcinogens on bladder cancer risk.

Urinary Exosomes: The Potential for Biomarker Utility, Intercellular Signaling and Therapeutics in Urological Malignancy.

PubMed

Franzen, Carrie A; Blackwell, Robert H; Foreman, Kimberly E; Kuo, Paul C; Flanigan, Robert C; Gupta, Gopal N

2016-05-01

Exosomes are small secreted vesicles that contain proteins, mRNA and miRNA with the potential to alter signaling pathways in recipient cells. While exosome research has flourished, few publications have specifically considered the role of genitourinary cancer shed exosomes in urine, their implication in disease progression and their usefulness as noninvasive biomarkers. In this review we examined the current literature on the role of exosomes in intercellular communication and as biomarkers, and their potential as delivery vehicles for therapeutic applications in bladder, prostate and renal cancer. We searched PubMed® and Google® with the key words prostate cancer, bladder cancer, kidney cancer, exosomes, microvesicles and urine. Relevant articles, including original research studies and reviews, were selected based on contents. A review of this literature was generated. Cancer exosomes can be isolated from urine using various techniques. Cancer cells have been found to secrete more exosomes than normal cells. These exosomes have a role in cellular communication by interacting with and depositing their cargo in target cells. Bladder, prostate and renal cancer exosomes have been shown to enhance migration, invasion and angiogenesis. These exosomes have also been shown to increase proliferation, confer drug resistance and promote immune evasion. Urinary exosomes can be isolated from bladder, kidney and prostate cancer. They serve as a potential reservoir for biomarker identification. Exosomes also have potential for therapeutics as siRNA or pharmacological agents can be loaded into exosomes. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Current Trends in the Incidence and Survival Rate of Urological Cancers in Korea.

PubMed

Joung, Jae Young; Lim, Jiwon; Oh, Chang-Mo; Jung, Kyu-Won; Cho, Hyunsoon; Kim, Sung Han; Seo, Ho Kyung; Park, Weon Seo; Chung, Jinsoo; Lee, Kang Hyun; Won, Young-Joo

2017-07-01

This descriptive study assessed the current trends in the incidence of urological cancers and patient survival in Korea. In this nationwide retrospective observational study based on the data from the Korea National Cancer Incidence Database (KNCIDB), this study analyzed the age-standardized incidence rates (ASRs) and annual percentage changes (APCs) of kidney, bladder, prostate, testicular, and penile cancers as well as cancer of the renal pelvis and ureter between 1999 and 2012. The relative survival rates (RSRs) were calculated for urological cancer patients diagnosed between 1993 and 2012 from the KNCIDB data. Prostate cancer was diagnosed in 66,812 individuals followed by bladder (41,549) and kidney (36,836) cancers. The overall ASR (18.26 per 100,000) increased with age because of the higher ASRs of bladder and prostate cancers in the elderly. The ASR for kidney cancer was highest in the 40-59-year-old group, whereas testicular cancer occurred most frequently before the age of 40. The incidence of most urological cancers increased (overall APC, 6.39%; p < 0.001), except for penile (APC, -2.01%; p=0.05) and bladder (APC, -0.40%; p=0.25) cancers. The overall survival increased steadily (5-year RSR, 66.4% in 1993-1995 vs. 84.2% in 2008-2012; p < 0.001), particularly for prostate (by 34.10%) and kidney (by 16.30%) cancers, but not for renal pelvis and ureter cancers (-7.20%). The most common urological cancer in Korea was prostate cancer followed by bladder and kidney cancers. The incidence of most urological cancers, except for penile and bladder cancers, increased. Survival also increased, particularly for prostate and kidney cancers.

Functional and molecular characterization of kinin B1 and B 2 receptors in human bladder cancer: implication of the PI3Kγ pathway.

PubMed

Sgnaolin, V; Pereira, T C B; Bogo, M R; Zanin, R; Battastini, A M O; Morrone, F B; Campos, M M

2013-08-01

Kinins and their receptors have been recently implicated in cancer. Using functional and molecular approaches, we investigated the relevance of kinin B1 and B2 receptors in bladder cancer. Functional studies were conducted using bladder cancer cell lines, and human biopsies were employed for molecular studies. Both B1 des-Arg(9)-BK and B2 BK receptor agonists stimulated the proliferation of grade 3-derived T24 bladder cancer cells. Furthermore, treatment with B1 and B2 receptor antagonists (SSR240612 and HOE140) markedly inhibited the proliferation of T24 cells. Only higher concentrations of BK increased the proliferation of the grade 1 bladder cancer cell line RT4, while des-Arg(9)-BK completely failed to induce its proliferation. Real-time PCR revealed that the mRNA expression of kinin receptors, particularly B1 receptors, was increased in T24 cells relative to RT4 cells. Data from bladder cancer human biopsies revealed that B1 receptor expression was increased in all tumor samples and under conditions of chronic inflammation. We also show novel evidence demonstrating that the pharmacological inhibition of PI3Kγ (phosphatidylinositol 3-kinase) with AS252424, concentration-dependently reduced T24 cell proliferation induced by BK or des-Arg(9)-BK. Finally, the incubation of T24 cells with kinin agonists led to a marked activation of the PI3K/AKT and ERK 1/2 signaling pathways, whereas p38 MAP kinase remained unaffected. Kinin receptors, especially B1 receptors, appear to be implicated in bladder cancer progression. It is tempting to suggest that selective kinin antagonists might represent potential alternative therapies for bladder cancer.

Insights from animal models of bladder cancer: recent advances, challenges, and opportunities

PubMed Central

John, Bincy Anu; Said, Neveen

2017-01-01

Bladder cancer (urothelial cancer of the bladder) is the most common malignancy affecting the urinary system with increasing incidence and mortality. Treatment of bladder cancer has not advanced in the past 30 years. Therefore, there is a crucial unmet need for novel therapies, especially for high grade/stage disease that can only be achieved by preclinical model systems that faithfully recapitulate the human disease. Animal models are essential elements in bladder cancer research to comprehensively study the multistep cascades of carcinogenesis, progression and metastasis. They allow for the investigation of premalignant phases of the disease that are not clinically encountered. They can be useful for identification of diagnostic and prognostic biomarkers for disease progression and for preclinical identification and validation of therapeutic targets/candidates, advancing translation of basic research to clinic. This review summarizes the latest advances in the currently available bladder cancer animal models, their translational potential, merits and demerits, and the prevalent tumor evaluation modalities. Thereby, findings from these model systems would provide valuable information that can help researchers and clinicians utilize the model that best answers their research questions. PMID:28915710

Image-guided photo-therapeutic nanoporphyrin synergized HSP90 inhibitor in patient-derived xenograft bladder cancer model.

PubMed

Long, Qilai; Lin, Tzu-Yin; Huang, Yee; Li, Xiaocen; Ma, Ai-Hong; Zhang, Hongyong; Carney, Randy; Airhart, Susan; Lam, Kit S; deVere White, Ralph W; Pan, Chong-Xian; Li, Yuanpei

2018-04-01

Photodynamic therapy is a promising and effective non-invasive therapeutic approach for the treatment of bladder cancers. Therapies targeting HSP90 have the advantage of tumor cell selectivity and have shown great preclinical efficacy. In this study, we evaluated a novel multifunctional nanoporphyrin platform loaded with an HSP90 inhibitor 17AAG (NP-AAG) for use as a multi-modality therapy against bladder cancer. NP-AAG was efficiently accumulated and retained at bladder cancer patient-derived xenograft (PDX) over 7 days. PDX tumors could be synergistically eradicated with a single intravenous injection of NP-AAG followed by multiple light treatments within 7 days. NP-AAG mediated treatment could not only specifically deliver 17AAG and produce heat and reactive oxygen species, but also more effectively inhibit essential bladder cancer essential signaling molecules like Akt, Src, and Erk, as well as HIF-1α induced by photo-therapy. This multifunctional nanoplatform has high clinical relevance and could dramatically improve management for bladder cancers with minimal toxicity. Copyright © 2018 Elsevier Inc. All rights reserved.

An Inexpensive, Point-of-Care Urine Test for Bladder Cancer in Patients Undergoing Hematuria Evaluation.

PubMed

Acharya, Abhinav P; Theisen, Kathryn M; Correa, Andres; Meyyappan, Thiagarajan; Apfel, Abraham; Sun, Tao; Tarin, Tatum V; Little, Steven R

2017-11-01

Although hematuria (blood in urine) is the most common symptom of bladder cancer, 70-98% of hematuria cases are benign. These hematuria patients unnecessarily undergo costly, invasive, and expensive evaluation for bladder cancer. Therefore, there remains a need for noninvasive office-based tests that can rapidly and reliably rule out bladder cancer in patients undergoing hematuria evaluation. Herein, a clinical assay for matrix metalloproteinases ("Ammps") is presented, which generates a visual signal based on the collagenase activity (in urine of patients) on the Ammps substrates. Ammps substrates are generated by crosslinking gelatin with Fe(II) chelated alginate nanoparticles, which precipitate in urine samples. The cleavage of gelatin-conjugated alginate (Fe(II)) nanoparticles by collagenases generates free-floating alginate (Fe(II)) nanoparticles that participate in Fenton's reaction to generate a visual signal. In a pilot study of 88 patients, Ammps had 100% sensitivity, 85% specificity, and a negative predictive value (NPV) of 100% for diagnosing bladder cancer. This high NPV can be useful in ruling out bladder cancer in patients referred for hematuria evaluation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Management of Bladder Cancer After Renal Transplantation.

PubMed

Demirdag, C; Citgez, S; Talat, Z; Onal, B

2017-03-01

In renal transplant recipients, the risk of developing bladder cancer and rate of diagnosis of advanced staged bladder cancer are generally higher than the general population. Also, it is more challenging to treat renal transplant recipients than the regular patient population. We aimed to evaluate the efficacy and safety of radical cystectomy (RC) and urinary diversion with ileal conduit in renal transplant recipients. We identified 2 patients with prior history of renal transplantation who underwent RC and ileal conduit urinary diversion for bladder cancer. Preoperative clinical and demographic data were presented and outcomes were assessed. The RC and ileal conduit urinary diversion were performed in the first patient 56 months after renal transplantation and in the second patient 64 months after renal transplantation. Clinical staging was high-grade T2 transitional cell cancer of the bladder for patient 1 and T2 with pure squamous cell cancer of the bladder for patient 2. No perioperative or postoperative complication and no graft dysfunction occurred in either patient. Our experience demonstrated that RC with ileal conduit reconstruction in renal transplant recipients is safe and feasible. Copyright © 2016 Elsevier Inc. All rights reserved.

Urological cancer care pathways: development and use in the context of systematic reviews and clinical practice guidelines.

PubMed

Maclennan, Sara Jane; Maclennan, Steven J; Imamura, Mari; Omar, Muhammad Imran; Vale, Luke; Lam, Thomas; Royle, Pamela; Royle, Justine; Swami, Satchi; Pickard, Rob; McClinton, Sam; Griffiths, T R Leyshon; Dahm, Philipp; N'dow, James

2011-06-01

Making healthcare treatment decisions is a complex process involving a broad stakeholder base including patients, their families, health professionals, clinical practice guideline developers and funders of healthcare. This paper presents a review of a methodology for the development of urological cancer care pathways (UCAN care pathways), which reflects an appreciation of this broad stakeholder base. The methods section includes an overview of the steps in the development of the UCAN care pathways and engagement with clinical content experts and patient groups. The development process is outlined, the uses of the urological cancer care pathways discussed and the implications for clinical practice highlighted. The full set of UCAN care pathways is published in this paper. These include care pathways on localised prostate cancer, locally advanced prostate cancer, metastatic prostate cancer, hormone-resistant prostate cancer, localised renal cell cancer, advanced renal cell cancer, testicular cancer, penile cancer, muscle invasive and metastatic bladder cancer and non-muscle invasive bladder cancer. The process provides a useful framework for improving urological cancer care through evidence synthesis, research prioritisation, stakeholder involvement and international collaboration. Although the focus of this work is urological cancers, the methodology can be applied to all aspects of urology and is transferable to other clinical specialties.

Advancements in optical techniques and imaging in the diagnosis and management of bladder cancer.

PubMed

Rose, Tracy L; Lotan, Yair

2018-03-01

Accurate detection and staging is critical to the appropriate management of urothelial cancer (UC). The use of advanced optical techniques during cystoscopy is becoming more widespread to prevent recurrent nonmuscle invasive bladder cancer. Standard of care for muscle-invasive UC includes the use of computed tomography and/or magnetic resonance imaging, but staging accuracy of these tests remains imperfect. Novel imaging modalities are being developed to improve current test performance. Positron emission tomography/computed tomography has a role in the initial evaluation of select patients with muscle-invasive bladder cancer and in disease recurrence in some cases. Several novel immuno-positron emission tomography tracers are currently in development to address the inadequacy of current imaging modalities for monitoring of tumor response to newer immune-based treatments. This review summaries the current standards and recent advances in optical techniques and imaging modalities in localized and metastatic UC. Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed

Jakszyn, Paula; González, Carlos A; Luján-Barroso, Leila; Ros, Martine M; Bueno-de-Mesquita, H Bas; Roswall, Nina; Tjønneland, Anne M; Büchner, Frederike L; Egevad, Lars; Overvad, Kim; Raaschou-Nielsen, Ole; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Touillaud, Marina S; Chang-Claude, Jenny; Allen, Naomi E; Kiemeney, Lambertus A; Key, Timothy J; Kaaks, Rudolf; Boeing, Heiner; Weikert, Steffen; Trichopoulou, Antonia; Oikonomou, Eleni; Zylis, Dimosthenis; Palli, Domenico; Berrino, Franco; Vineis, Paolo; Tumino, Rosario; Mattiello, Amalia; Peeters, Petra H M; Parr, Christine L; Gram, Inger T; Skeie, Guri; Sánchez, Maria-Jose; Larrañaga, Nerea; Ardanaz, Eva; Navarro, Carmen; Rodríguez, Laudina; Ulmert, David; Ehrnström, Roy; Hallmans, Göran; Ljungberg, Borje; Roddam, Andrew Wilfred; Bingham, Sheila A; Khaw, Kay-Tee; Slimani, Nadia; Boffetta, Paolo A; Jenab, Mazda; Mouw, Traci; Michaud, Dominique S; Riboli, Elio

2011-03-01

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, dietary nitrosamines, and heme iron and the risk of bladder cancer among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). Data on food consumption and complete follow-up for cancer occurrence were available for a total of 481,419 participants, recruited in 10 European countries. Estimates of HRs were obtained by proportional hazard models, stratified by age at recruitment, gender, and study center and adjusted for total energy intake, smoking status, lifetime intensity of smoking, duration of smoking, educational level, and BMI. After a mean follow-up of 8.7 years, 1,001 participants were diagnosed with bladder cancer. We found no overall association between intake of red meat (log2 HR: 1.06; 95% CI: 0.99-1.13), nitrosamines (log2 HR: 1.09; 95% CI: 0.92-1.30 and HR: 0.98; 95% CI: 0.92-1.05 for ENOC and NDMA, respectively) or heme iron (log2 HR: 1.05; 95 CI: 0.99-1.12) and bladder cancer risk. The associations did not vary by sex, high- versus low-risk bladder cancers, smoking status, or occupation (high vs. low risk). Our findings do not support an effect of red meat intake, nitrosamines (endogenous or exogenous), or heme iron intake on bladder cancer risk. ©2011 AACR.

HAMLET treatment delays bladder cancer development.

PubMed

Mossberg, Ann-Kristin; Hou, Yuchuan; Svensson, Majlis; Holmqvist, Bo; Svanborg, Catharina

2010-04-01

HAMLET is a protein-lipid complex that kills different types of cancer cells. Recently we observed a rapid reduction in human bladder cancer size after intravesical HAMLET treatment. In this study we evaluated the therapeutic effect of HAMLET in the mouse MB49 bladder carcinoma model. Bladder tumors were established by intravesical injection of MB49 cells into poly L-lysine treated bladders of C57BL/6 mice. Treatment groups received repeat intravesical HAMLET instillations and controls received alpha-lactalbumin or phosphate buffer. Effects of HAMLET on tumor size and putative apoptotic effects were analyzed in bladder tissue sections. Whole body imaging was used to study HAMLET distribution in tumor bearing mice compared to healthy bladder tissue. HAMLET caused a dose dependent decrease in MB49 cell viability in vitro. Five intravesical HAMLET instillations significantly decreased tumor size and delayed development in vivo compared to controls. TUNEL staining revealed selective apoptotic effects in tumor areas but not in adjacent healthy bladder tissue. On in vivo imaging Alexa-HAMLET was retained for more than 24 hours in the bladder of tumor bearing mice but not in tumor-free bladders or in tumor bearing mice that received Alexa-alpha-lactalbumin. Results show that HAMLET is active as a tumoricidal agent and suggest that topical HAMLET administration may delay bladder cancer development. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prognostic and therapeutic impact of argininosuccinate synthetase 1 control in bladder cancer as monitored longitudinally by PET imaging.

PubMed

Allen, Michael D; Luong, Phuong; Hudson, Chantelle; Leyton, Julius; Delage, Barbara; Ghazaly, Essam; Cutts, Rosalind; Yuan, Ming; Syed, Nelofer; Lo Nigro, Cristiana; Lattanzio, Laura; Chmielewska-Kassassir, Malgorzata; Tomlinson, Ian; Roylance, Rebecca; Whitaker, Hayley C; Warren, Anne Y; Neal, David; Frezza, Christian; Beltran, Luis; Jones, Louise J; Chelala, Claude; Wu, Bor-Wen; Bomalaski, John S; Jackson, Robert C; Lu, Yong-Jie; Crook, Tim; Lemoine, Nicholas R; Mather, Stephen; Foster, Julie; Sosabowski, Jane; Avril, Norbert; Li, Chien-Feng; Szlosarek, Peter W

2014-02-01

Targeted therapies have yet to have significant impact on the survival of patients with bladder cancer. In this study, we focused on the urea cycle enzyme argininosuccinate synthetase 1 (ASS1) as a therapeutic target in bladder cancer, based on our discovery of the prognostic and functional import of ASS1 in this setting. ASS1 expression status in bladder tumors from 183 Caucasian and 295 Asian patients was analyzed, along with its hypothesized prognostic impact and association with clinicopathologic features, including tumor size and invasion. Furthermore, the genetics, biology, and therapeutic implications of ASS1 loss were investigated in urothelial cancer cells. We detected ASS1 negativity in 40% of bladder cancers, in which multivariate analysis indicated worse disease-specific and metastasis-free survival. ASS1 loss secondary to epigenetic silencing was accompanied by increased tumor cell proliferation and invasion, consistent with a tumor-suppressor role for ASS1. In developing a treatment approach, we identified a novel targeted antimetabolite strategy to exploit arginine deprivation with pegylated arginine deiminase (ADI-PEG20) as a therapeutic. ADI-PEG20 was synthetically lethal in ASS1-methylated bladder cells and its exposure was associated with a marked reduction in intracellular levels of thymidine, due to suppression of both uptake and de novo synthesis. We found that thymidine uptake correlated with thymidine kinase-1 protein levels and that thymidine levels were imageable with [(18)F]-fluoro-L-thymidine (FLT)-positron emission tomography (PET). In contrast, inhibition of de novo synthesis was linked to decreased expression of thymidylate synthase and dihydrofolate reductase. Notably, inhibition of de novo synthesis was associated with potentiation of ADI-PEG20 activity by the antifolate drug pemetrexed. Taken together, our findings argue that arginine deprivation combined with antifolates warrants clinical investigation in ASS1-negative urothelial and related cancers, using FLT-PET as an early surrogate marker of response.

Bladder cancer among hairdressers: a meta-analysis

PubMed Central

Schablon, Anja; Schedlbauer, Grita; Dulon, Madeleine; Nienhaus, Albert

2010-01-01

Background Occupational risks for bladder cancer in hairdressers by using hair products have been examined in many epidemiological studies. But owing to small sample sizes of the studies and the resulting lack of statistical power, the results of these studies have been inconsistent and significant associations have rarely been found. Methods We conducted a meta-analysis to determine summary risk ratios (SRRs) for the risk of bladder cancer among hairdressers. Studies were identified by a MEDLINE, EMBASE, CENTRAL search and by the reference lists of articles/relevant reviews. Statistical tests for publication bias and for heterogeneity as well as sensitivity analysis were applied. In addition, the study quality and the risk of bias were assessed using six criteria. Results 42 studies were included and statistically significantly increased risks around 1.3–1.7 were found for all but one analysis. The SRR increased with duration of employment from 1.30 (95% CI 1.15 to 1.48) for ‘ever registered as hairdresser’ to 1.70 (95% CI 1.01 to 2.88) for ‘job held ≥10 years’. No difference was found between the risk for smoking-adjusted data (SRR 1.35, 95% CI 1.13 to 1.61) and no adjustment (SRR 1.33, 95% CI 1.18 to 1.50). Studies assessed as being of high quality (n=11) and of moderate quality (n=31) showed similar SRRs. There was no evidence of publication bias or heterogeneity in all analyses. Conclusion In summary, our results showed an increased and statistically significant risk for bladder cancer among hairdressers, in particular for hairdressers in jobs held ≥10 years. Residual confounding by smoking cannot be totally ruled out. Because of the long latency times of bladder cancer it remains an open question whether hairdressers working prior to 1980 and after 1980, when some aromatic amines were banned as hair dye ingredients, have the same risk for bladder cancer. PMID:20447989

N-acetyltransferase 1*10 genotype in bladder cancer patients.

PubMed

Höhne, Svetlana; Gerullis, Holger; Blaszkewicz, Meinolf; Selinski, Silvia; Hengstler, Jan G; Otto, Thomas; Golka, Klaus

2017-01-01

In a large bladder cancer study in the greater Berlin area with 425 cases and 343 controls, the haplotype N-acetyltransferase 1*10 (NAT1*10) was associated with a decreased bladder cancer risk. In a recently published meta-analysis, results of the studies were found to be inconclusive. Therefore, the aim of this study was to investigate the frequency of NAT1*10 in bladder cancer patients and controls recruited in an area without industries reported to be associated with increased bladder cancer risk. Rs1057126 (1088 T > A) and rs15561 (1095 C > A) were determined in 412 bladder cancer patients and 415 controls without a known history of malignancies. With these two single-nucleotide polymorphisms (SNP), it was possible to distinguish between NAT1*4 (wild type), NAT1*3 (1095 C > A), and NAT1*10 (1088 T > A, 1095C > A). The frequencies of the determined NAT1 haplotypes did not differ markedly between cases and controls: NAT1*4: 74%, NAT1*3: 6%, NAT1*10: 20%. Bladder cancer risk was not significantly modulated by NAT1*10/*10 (OR 1.03, 95% CI 0.71-1.48) but was higher for NAT1*3/*3 genotypes (OR 2.05, 95% CI 1.32-3.21). In contrast to the Berlin study from 2001, data in present study demonstrated that NAT1*10 haplotype was not associated with a significantly decreased bladder cancer risk. This may be due to local effects in the greater Berlin area, particularly at the time of investigation. The findings of the present study are in agreement with observations of a recently published meta-analysis which also showed no relevant impact of NAT1*10 haplotype on bladder cancer risk. The impact of the rare NAT1*3/*3 genotype was significant but this may be attributed to rarity without major practical relevance.

Bladder cancer SNP panel predicts susceptibility and survival

PubMed Central

Andrew, Angeline S.; Gui, Jiang; Sanderson, Arthur C.; Mason, Rebecca A.; Morlock, Elaine V.; Schned, Alan R.; Kelsey, Karl T.; Marsit, Carmen J.; Moore, Jason H.; Karagas, Margaret R.

2009-01-01

Bladder cancer is the fourth most common malignancy in men and the eighth most common in women in western countries. Single nucleotide polymorphisms (SNPs) in genes that regulate telomere maintenance, mitosis, inflammation, and apoptosis have not been assessed extensively for this disease. Using a population-based study with 832 bladder cancer cases and 1,191 controls, we assessed genetic variation in relation to cancer susceptibility or survival. Findings included an increased risk associated with variants in the methyl-metabolism gene, MTHFD2 (OR 1.7 95% CI 1.3–2.3), the telomerase TEP1 (OR 1.8 95% CI 1.2–2.6) and decreased risk associated with the inflammatory response gene variant IL8RB (OR 0.6 95% CI 0.5–0.9) compared to wild-type. Shorter survival was associated with apoptotic gene variants, including CASP9 (HR 1.8 95% CI 1.1–3.0). Variants in the detoxification gene EPHX1 experienced longer survival (HR 0.4 (95% CI 0.2–0.8). These genes can now be assessed in multiple study populations to identify and validate SNPs appropriate for clinical use. PMID:19252927

Functional genomics annotation of a statistical epistasis network associated with bladder cancer susceptibility.

PubMed

Hu, Ting; Pan, Qinxin; Andrew, Angeline S; Langer, Jillian M; Cole, Michael D; Tomlinson, Craig R; Karagas, Margaret R; Moore, Jason H

2014-04-11

Several different genetic and environmental factors have been identified as independent risk factors for bladder cancer in population-based studies. Recent studies have turned to understanding the role of gene-gene and gene-environment interactions in determining risk. We previously developed the bioinformatics framework of statistical epistasis networks (SEN) to characterize the global structure of interacting genetic factors associated with a particular disease or clinical outcome. By applying SEN to a population-based study of bladder cancer among Caucasians in New Hampshire, we were able to identify a set of connected genetic factors with strong and significant interaction effects on bladder cancer susceptibility. To support our statistical findings using networks, in the present study, we performed pathway enrichment analyses on the set of genes identified using SEN, and found that they are associated with the carcinogen benzo[a]pyrene, a component of tobacco smoke. We further carried out an mRNA expression microarray experiment to validate statistical genetic interactions, and to determine if the set of genes identified in the SEN were differentially expressed in a normal bladder cell line and a bladder cancer cell line in the presence or absence of benzo[a]pyrene. Significant nonrandom sets of genes from the SEN were found to be differentially expressed in response to benzo[a]pyrene in both the normal bladder cells and the bladder cancer cells. In addition, the patterns of gene expression were significantly different between these two cell types. The enrichment analyses and the gene expression microarray results support the idea that SEN analysis of bladder in population-based studies is able to identify biologically meaningful statistical patterns. These results bring us a step closer to a systems genetic approach to understanding cancer susceptibility that integrates population and laboratory-based studies.

Apoptosis triggered by isoquercitrin in bladder cancer cells by activating the AMPK-activated protein kinase pathway.

PubMed

Wu, Ping; Liu, Siyuan; Su, Jianyu; Chen, Jianping; Li, Lin; Zhang, Runguang; Chen, Tianfeng

2017-10-18

Cancer cells are well known to require a constant supply of protein, lipid, RNA, and DNA via altered metabolism for accelerated cell proliferation. Targeting metabolic pathways is, therefore, a promising therapeutic strategy for cancers. Isoquercitrin (ISO) is widely distributed in dietary and medicinal plants and displays selective cytotoxicity to cancer cells, primarily by inducing apoptosis and cell cycle arrest. The aims of this study were to find out whether ISO could stabilize in a bladder-like acidic environment and inhibit bladder cancer cell proliferation by affecting their metabolism, and to investigate its molecular mechanism. In this study, the exposure of T24 bladder cancer cells to ISO (20-80 μM) decreased cell viability by causing ROS overproduction. This ROS change regulated the AMPK signaling pathway, and caused Caspase-dependent apoptosis as well as metabolism dysfunction. Metabolic alterations elevated metabolic pathway variation, which in turn destabilized lipid synthesis and altered anaerobic glycolysis. This linkage was proved by immunoblotting assay, and metabolomics as identified by UHPLC-QTOF-MS. Our findings provide comprehensive evidence that ISO influenced T24 bladder cancer cell metabolism, and that this process was mainly involved in activating the AMPK pathway. This study could lead to an understanding of how ISO suppresses bladder cancer cell growth, and whether the affected cancer metabolism is a common mechanism by which nutritional compounds suppress cancers.

Detection of bladder metabolic artifacts in (18)F-FDG PET imaging.

PubMed

Roman-Jimenez, Geoffrey; Crevoisier, Renaud De; Leseur, Julie; Devillers, Anne; Ospina, Juan David; Simon, Antoine; Terve, Pierre; Acosta, Oscar

2016-04-01

Positron emission tomography using (18)F-fluorodeoxyglucose ((18)F-FDG-PET) is a widely used imaging modality in oncology. It enables significant functional information to be included in analyses of anatomical data provided by other image modalities. Although PET offers high sensitivity in detecting suspected malignant metabolism, (18)F-FDG uptake is not tumor-specific and can also be fixed in surrounding healthy tissue, which may consequently be mistaken as cancerous. PET analyses may be particularly hampered in pelvic-located cancers by the bladder׳s physiological uptake potentially obliterating the tumor uptake. In this paper, we propose a novel method for detecting (18)F-FDG bladder artifacts based on a multi-feature double-step classification approach. Using two manually defined seeds (tumor and bladder), the method consists of a semi-automated double-step clustering strategy that simultaneously takes into consideration standard uptake values (SUV) on PET, Hounsfield values on computed tomography (CT), and the distance to the seeds. This method was performed on 52 PET/CT images from patients treated for locally advanced cervical cancer. Manual delineations of the bladder on CT images were used in order to evaluate bladder uptake detection capability. Tumor preservation was evaluated using a manual segmentation of the tumor, with a threshold of 42% of the maximal uptake within the tumor. Robustness was assessed by randomly selecting different initial seeds. The classification averages were 0.94±0.09 for sensitivity, 0.98±0.01 specificity, and 0.98±0.01 accuracy. These results suggest that this method is able to detect most (18)F-FDG bladder metabolism artifacts while preserving tumor uptake, and could thus be used as a pre-processing step for further non-parasitized PET analyses. Copyright © 2016. Published by Elsevier Ltd.

Efficacy and safety of hexaminolevulinate fluorescence cystoscopy in the diagnosis of bladder cancer.

PubMed

Lee, Jae Seung; Lee, Seo Yeon; Kim, Woo Jung; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han Yong; Jeong, Byong Chang

2012-12-01

The aim of this study was to evaluate the efficacy and safety of hexaminolevulinate fluorescence cystoscopy in the diagnosis of bladder cancer. In a prospective design, we included patients who had a bladder lesion suggesting bladder cancer. Patients with massive hematuria, urethral Foley catheter insertion, chronic retention state, or urinary tract infection were excluded. After the bladder was emptied, hexaminolevulinate was gently administered into the bladder. One hour later, cystoscopy under white light and blue light was performed. After marking the lesions confirmed with white light or blue light, transurethral resection of the bladder lesion and pathologic confirmation were done. Transurethral resection of the lesions that were negative in both white and blue light was also performed. From April 2010 to September 2010, 30 patients were enrolled. From the total of 30 patients (25 men and 5 women; mean age, 60.4±9.22 years), 134 specimens were extracted. Among these, 101 specimens showed positive results by blue light cystoscopy (BLC). The sensitivity of BLC and white light cystoscopy (WLC) was 92.3% and 80.8%, respectively (p=0.021). The specificity of BLC and WLC was 48% and 49.1%, respectively (p>0.05). The positive and negative predictive values of BLC were 71.2% and 81.8%, respectively, whereas those of WLC were 72.0% and 68.6%, respectively. With WLC, 48 specimens showed negative findings, but of that group, 15 specimens (31.2%) were revealed to be malignant with BLC. There were no significant side effects in the 24 hours after the instillation of hexaminolevulinate. Photodynamic diagnosis with hexaminolevulinate helps to find tumors that could be missed by use of WLC only. Photodynamic diagnosis might be valuable in complete resection as well as for more accurate diagnosis of bladder tumor.

Epithelial-mesenchymal transition, a novel target of sulforaphane via COX-2/MMP2, 9/Snail, ZEB1 and miR-200c/ZEB1 pathways in human bladder cancer cells.

PubMed

Shan, Yujuan; Zhang, Lanwei; Bao, Yongping; Li, Baolong; He, Canxia; Gao, Mingming; Feng, Xue; Xu, Weili; Zhang, Xiaohong; Wang, Shuran

2013-06-01

Metastasis and recurrence of bladder cancer are the main reasons for its poor prognosis and high mortality rates. Because of its biological activity and high metabolic accumulation in urine, sulforaphane, a phytochemical exclusively occurring in cruciferous vegetables, has a powerful and specific potential for preventing bladder cancer. In this paper, sulforaphane is shown to significantly suppress a variety of biochemical pathways including the attachment, invasion, migration and chemotaxis motion in malignant transitional bladder cancer T24 cells. Transfection with cyclooxygenase-2 (COX-2) overexpression plasmid largely abolished inhibition of MMP2/9 expression as well as cell invasive capability by sulforaphane. Moreover, sulforaphane inhibited the epithelial-to-mesenchymal transition (EMT) process which underlies tumor cell invasion and migration mediated by E-cadherin induction through reducing transcriptional repressors, such as ZEB1 and Snail. Under conditions of over-expression of COX-2 and/or MMP2/9, sulforaphane was still able to induce E-cadherin or reduce Snail/ZEB1 expression, suggesting that additional pathways might be involved. Further studies indicated that miR-200c played a role in the regulation of E-cadherin via the ZEB1 repressor but not by the Snail repressor. In conclusion, the EMT and two recognized signaling pathways (COX-2/MMP2,9/ ZEB1, Snail and miR-200c/ZEB1) are all targets for sulforaphane. This study indicated that sulforaphane may possess therapeutic potential in preventing recurrence of human bladder cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

Urinary arsenic profiles and the risks of cancer mortality: A population-based 20-year follow-up study in arseniasis-endemic areas in Taiwan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Chi-Jung; Department of Medical Research, China Medical Hospital, Taichung, Taiwan; Huang, Ya-Li

2013-04-15

Few studies investigated the association between chronic arsenic exposure and the mortality of cancers by estimating individual urinary arsenic methylation profiles. Therefore, we compared with the general population in Taiwan to calculate the standardized mortality ratio (SMR) in arseniasis-endemic area of Taiwan from 1996 to 2010 and evaluated the dose-response relationships between environmental arsenic exposure indices or urinary arsenic profiles and the mortality of cause-specific cancer. A cohort of 1563 residents was conducted and collected their urine sample and information regarding arsenic exposure from a questionnaire. All-cause death was identified using the National Death Registry of Taiwan. Urinary arsenic profilesmore » were measured using high performance liquid chromatography–hydride generator–atomic absorption spectrometry. We used Cox proportional hazard models to evaluate the mortality risks. In results, 193 all-site cancer deaths, and 29, 71, 43 deaths respectively for liver, lung and bladder cancers were ascertained. The SMRs were significantly high in arseniasis-endemic areas for liver, lung, and bladder cancers. People with high urinary InAs% or low DMA% or low secondary methylation index (SMI) were the most likely to suffer bladder cancer after adjusting other risk factors. Even stopping exposure to arsenic from the artesian well water, the mortality rates of the residents were higher than general population. Finally, urinary InAs%, DMA% and SMI could be the potential biomarkers to predict the mortality risk of bladder cancer. -- Highlights: ► The SMRs were significantly high in arseniasis-endemic areas for liver, lung, and bladder cancers. ► People with high urinary InAs% were the most likely to suffer bladder cancer. ► People with low DMA% or low SMI were the most likely to suffer bladder cancer.« less

Incidence analyses of bladder cancer in the Nile delta region of Egypt

PubMed Central

Fedewa, Stacey A.; Soliman, Amr S.; Ismail, Kadry; Hablas, Ahmed; Seifeldin, Ibrahim A.; Ramadan, Mohamed; Omar, Hoda G.; Nriagu, Jerome; Wilson, Mark L.

2009-01-01

Bladder cancer is the most common malignancy among Egyptian males and previously has been attributed to Schistosoma infection, a major risk factor for squamous cell carcinoma (SCC). Recently, transitional cell carcinoma (TCC) incidence has been increasing while SCC has declined. To investigate this shift, we analyzed the geographical patterns of all bladder cancers cases recorded in Egypt’s Gharbiah Population-Based Cancer Registry from 1999 through 2002. Data on tumor grade, stage, and morphology, as well as smoking, community of residence, age and sex, were collected on 1,209 bladder cancer cases. Age-adjusted incidence rates were calculated for males, females, and the total population for the eight administrative Districts and 316 communities in Gharbiah. Incidence Rate Ratios (IRR) and 95% Confidence Intervals (CI) were computed using Poisson Regression. The male age-adjusted incidence rate (IR) in Gharbiah Province was 13.65/100,000 person years (PY). The District of Kotour had the highest age-adjusted IR 28.96/100,000 among males. The District of Kotour also had the highest IRR among all Districts, IRR=2.15 95% CI (1.72, 2.70). Kotour’s capital city had the highest bladder cancer incidence among the 316 communities (IR=73.11/100,000 PY). Future studies on sources and types of environmental pollution and exposures in relation to the spatial patterns of bladder cancer, particularly in Kotour District, may improve our understating of risk factors for bladder cancer in the region. PMID:19762298

Complicated Genitourinary Tract Infections and Mimics.

PubMed

Yu, Michael; Robinson, Kathryn; Siegel, Cary; Menias, Christine

This article provides pictorial review of complicated upper and lower genitourinary infections and their mimics. Imaging features of upper urinary tract infections including uncomplicated acute pyelonephritis, xanthogranulomatous pyelonephritis (XGPN), emphysematous pyelonephritis, perirenal abscess, and pyonephrosis are first reviewed and then followed by pictorial review of their mimics including contrast-associated nephrotoxicity, renal infarcts, malakoplakia, renal cell cancer, leukemia or lymphoma and Castleman's disease. Next, imaging features of lower urinary tract infections including cystitis, emphysematous cystitis, enterovesical, colovesical and vesicovaginal fistulas, Fournier gangrene, prostatitis, epididymitis, and orchitis are reviewed and then followed by pictorial review of their mimics including gas in the bladder and perineum related to instrumentation, radiation cystitis, bladder cancer, testicular torsion, testicular trauma, and testicular cancer and lymphoma. Recognizing imaging characteristics of complicated genitourinary infections and their mimics would allow clinicians to provide appropriate timely management. Copyright © 2016 Elsevier Inc. All rights reserved.

Immunotherapy: a new treatment paradigm in bladder cancer

PubMed Central

Davarpanah, Nicole N.; Yuno, Akira; Trepel, Jane B.; Apolo, Andrea B.

2017-01-01

Purpose of review T-cell checkpoint blockade has become a dynamic immunotherapy for bladder cancer. In 2016, atezolizumab, an immune checkpoint inhibitor, became the first new drug approved in metastatic urothelial carcinoma (mUC) in over 30 years. In 2017, nivolumab was also approved for the same indication. This overview of checkpoint inhibitors in clinical trials focuses on novel immunotherapy combinations, predictive biomarkers including mutational load and neoantigen identification, and an evaluation of the future of bladder cancer immunotherapy. Recent findings Programed cell death protein 1/programed death-ligand 1 (PD-1/PD-L1) checkpoint inhibitors have achieved durable clinical responses in a subset of previously treated and treatment-naïve patients with mUC. The combination of PD-1 and cytotoxic T-lymphocyte antigen 4 (CTLA-4) has successfully improved response rates in multiple malignancies, and combination studies are underway in many tumor types, including bladder cancer, combining T-cell checkpoint blockade with other checkpoint agents and immunomodulatory therapies. Strong tumor responses to checkpoint blockade have been reported to be positively associated with expression of PD-L1 on tumor and tumor-infiltrating immune cells and with increased mutation-associated neoantigen load, which may lead to the development of predictive biomarkers. Summary Recent clinical evidence suggests that mUC is susceptible to T-cell checkpoint blockade. A global effort is underway to achieve higher response rates and more durable remissions, accelerate the development of immunotherapies, employ combination therapies, and test novel immune targets. PMID:28306559

Prognostic value of cell cycle regulatory proteins in muscle-infiltrating bladder cancer.

PubMed

Galmozzi, Fabia; Rubagotti, Alessandra; Romagnoli, Andrea; Carmignani, Giorgio; Perdelli, Luisa; Gatteschi, Beatrice; Boccardo, Francesco

2006-12-01

The aims of this study were to investigate the expression levels of proteins involved in cell cycle regulation in specimens of bladder cancer and to correlate them with the clinicopathological characteristics, proliferative activity and survival. Eighty-two specimens obtained from patients affected by muscle-invasive bladder cancer were evaluated immunohistochemically for p53, p21 and cyclin D1 expression, as well as for the tumour proliferation index, Ki-67. The statistical analysis included Kaplan-Meier curves with log-rank test and Cox proportional hazards models. In univariate analyses, low Ki-67 proliferation index (P = 0.045) and negative p21 immunoreactivity (P = 0.04) were associated to patient's overall survival (OS), but in multivariate models p21 did not reach statistical significance. When the combinations of the variables were assessed in two separate multivariate models that included tumour stage, grading, lymph node status, vascular invasion and perineural invasion, the combined variables p21/Ki-67 or p21/cyclin D1 expression were independent predictors for OS; in particular, patients with positive p21/high Ki-67 (P = 0.015) or positive p21/negative cyclin D1 (P = 0.04) showed the worst survival outcome. Important alterations in the cell cycle regulatory pathways occur in muscle-invasive bladder cancer and the combined use of cell cycle regulators appears to provide significant prognostic information that could be used to select the patients most suitable for multimodal therapeutic approaches.

Differential association for N-acetyltransferase 2 genotype and phenotype with bladder cancer risk in Chinese population.

PubMed

Quan, Lei; Chattopadhyay, Koushik; Nelson, Heather H; Chan, Kenneth K; Xiang, Yong-Bing; Zhang, Wei; Wang, Renwei; Gao, Yu-Tang; Yuan, Jian-Min

2016-06-28

N-acetyltransferase 2 (NAT2) is involved in both carcinogen detoxification through hepatic N-acetylation and carcinogen activation through local O-acetylation. NAT2 slow acetylation status is significantly associated with increased bladder cancer risk among European populations, but its association in Asian populations is inconclusive. NAT2 acetylation status was determined by both single nucleotide polymorphisms (SNPs) and caffeine metabolic ratio (CMR), in a population-based study of 494 bladder cancer patients and 507 control subjects in Shanghai, China. The CMR, a functional measure of hepatic N-acetylation, was significantly reduced in a dose-dependent manner among both cases and controls possessing the SNP-inferred NAT2 slow acetylation status (all P-values<5.0×10-10). The CMR-determined slow N-acetylation status (CMR<0.34) was significantly associated with a 50% increased risk of bladder cancer (odds ratio = 1.50, 95% confidence interval = 1.10-2.06) whereas the SNP-inferred slow acetylation statuses were significantly associated with an approximately 50% decreased risk of bladder cancer. The genotype-disease association was strengthened after the adjustment for CMR and was primarily observed among never smokers. The apparent differential associations for phenotypic and genetic measures of acetylation statuses with bladder cancer risk may reflect dual functions of NAT2 in bladder carcinogenesis because the former only measures the capacity of carcinogen detoxification pathway while the latter represents both carcinogen activation and detoxification pathways. Future studies are warranted to ascertain the specific role of N- and O-acetylation in bladder carcinogenesis, particularly in populations exposed to different types of bladder carcinogens.

Shared Occupational Risks for Transitional Cell Cancer of the Bladder and Renal Pelvis among Men and Women in Sweden

PubMed Central

Wilson, Robin Taylor; Donahue, Mark; Gridley, Gloria; Adami, Johanna; ghormli, Laure El; Dosemeci, Mustafa

2009-01-01

Background: Unlike cancer of the bladder, cancer of the renal pelvis is not considered an occupational cancer and little is known about risks among women. Methods: Using the Swedish national census and cancer registry-linked data (1971-1989), we identified transitional cell cancers of the renal pelvis (N=1374) and bladder (N=21,591). Correlation between cancer sites for the Standardized Incidence Ratios (SIR) were determined using Pearson's coefficient of the log SIR. Relative risks of job exposure matrix variables were calculated using Poisson regression. Results: Both cancer sites were significantly elevated among women and men employed in the machine/electronics industry, sedentary work, and indoor work, as well as among men employed in the shop and construction metal industry, contributing 10-14% of cases among men. Risks by industry were more highly correlated among women (r=0.49, p=0.002) than men (r=0.24, p=0.04). Conclusion: Cancers of the renal pelvis and bladder share common occupational risk factors that may be more frequent among women. In addition, there may be several jobs that pose an increased risk specifically for cancer of the renal pelvis but not bladder. PMID:18067176

Disruption of the FA/BRCA pathway in bladder cancer.

PubMed

Neveling, K; Kalb, R; Florl, A R; Herterich, S; Friedl, R; Hoehn, H; Hader, C; Hartmann, F H; Nanda, I; Steinlein, C; Schmid, M; Tonnies, H; Hurst, C D; Knowles, M A; Hanenberg, H; Schulz, W A; Schindler, D

2007-01-01

Bladder carcinomas frequently show extensive deletions of chromosomes 9p and/or 9q, potentially including the loci of the Fanconi anemia (FA) genes FANCC and FANCG. FA is a rare recessive disease due to defects in anyone of 13 FANC genes manifesting with genetic instability and increased risk of neoplasia. FA cells are hypersensitive towards DNA crosslinking agents such as mitomycin C and cisplatin that are commonly employed in the chemotherapy of bladder cancers. These observations suggest the possibility of disruption of the FA/BRCA DNA repair pathway in bladder tumors. However, mutations in FANCC or FANCG could not be detected in any of 23 bladder carcinoma cell lines and ten surgical tumor specimens by LOH analysis or by FANCD2 immunoblotting assessing proficiency of the pathway. Only a single cell line, BFTC909, proved defective for FANCD2 monoubiquitination and was highly sensitive towards mitomycin C. This increased sensitivity was restored specifically by transfer of the FANCF gene. Sequencing of FANCF in BFTC909 failed to identify mutations, but methylation of cytosine residues in the FANCF promoter region was demonstrated by methylation-specific PCR, HpaII restriction and bisulfite DNA sequencing. Methylation-specific PCR uncovered only a single instance of FANCF promoter hypermethylation in surgical specimens of further 41 bladder carcinomas. These low proportions suggest that in contrast to other types of tumors silencing of FANCF is a rare event in bladder cancer and that an intact FA/BRCA pathway might be advantageous for tumor progression. Copyright (c) 2007 S. Karger AG, Basel.

Exploration of risk factors predicting outcomes for primary T1 high-grade bladder cancer and validation of the Spanish Urological Club for Oncological Treatment scoring model: Long-term follow-up experience at a single institute.

PubMed

Miyake, Makito; Gotoh, Daisuke; Shimada, Keiji; Tatsumi, Yoshihiro; Nakai, Yasushi; Anai, Satoshi; Torimoto, Kazumasa; Aoki, Katsuya; Tanaka, Nobumichi; Konishi, Noboru; Fujimoto, Kiyohide

2015-06-01

To determine the prognostic factors of primary T1 high-grade bladder cancer and to validate the Spanish Urological Club for Oncological Treatment model in Japanese patients with T1 high-grade bladder cancer treated at a single institution. Records of 106 patients with T1 high-grade bladder cancer treated from 1998 to 2013 were retrospectively reviewed. Variables included various clinicopathological parameters, including lymphovascular invasion and tumor growth pattern at the invasion front. Recurrence-free survival and progression-free survival were analyzed. Multivariate Cox proportional regression analysis was used to verify the prognostic significance of the variables. Scores for recurrence and progression were calculated using the Spanish Urological Club for Oncological Treatment model. Of 106 patients, 44 (42%) had recurrence and 16 (15%) developed progression after a median (interquartile range) follow-up period of 54 months (range 32-81 months). Non-papillary shape was the only independent predictor for recurrence, while broad-based tumor stalk and infiltrative tumor growth pattern at the invasion front were determined to be independent predictors for progression. Stratification of patients according to the number of progression risk factors yielded hazard ratios of 10.1 and 13.1 in patients having one and two risks, respectively, compared with those without any risks. The Spanish Urological Club for Oncological Treatment model successfully stratified our patients with a trend toward different probabilities of recurrence and progression. The results of the present study might be helpful for counseling certain patients towards intensive treatment, such as radical cystectomy and/or platinum-based systemic chemotherapy. In addition, the Spanish Urological Club for Oncological Treatment model might be applicable to Japanese patients with T1 high-grade bladder cancer. © 2015 The Japanese Urological Association.

Bladder and Other Urothelial Cancers Screening (PDQ®)—Health Professional Version

Cancer.gov

Bladder and other urothelial cancers screening lacks evidence to show a reduction in mortality from these cancers. Get detailed information about urothelial cancer risk factors and screening tests in this clinician summary.

Nitrative DNA damage and Oct3/4 expression in urinary bladder cancer with Schistosomahaematobium infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Ning; Thanan, Raynoo; Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie

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 induciblemore » 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.« less

Fruit and Vegetable Intakes Are Associated with Lower Risk of Bladder Cancer among Women in the Multiethnic Cohort Study12

PubMed Central

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

2013-01-01

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. PMID:23739308

Androgen receptor activity modulates responses to cisplatin treatment in bladder cancer.

PubMed

Kashiwagi, Eiji; Ide, Hiroki; Inoue, Satoshi; Kawahara, Takashi; Zheng, Yichun; Reis, Leonardo O; Baras, Alexander S; Miyamoto, Hiroshi

2016-08-02

Cisplatin (CDDP)-based combination chemotherapy remains the mainstream treatment for advanced bladder cancer. However, its efficacy is often limited due to the development of resistance for which underlying mechanisms are poorly understood. Meanwhile, emerging evidence has indicated the involvement of androgen-mediated androgen receptor (AR) signals in bladder cancer progression. In this study, we aimed to investigate whether AR signals have an impact on sensitivity to CDDP in bladder cancer cells. UMUC3-control-short hairpin RNA (shRNA) cells with endogenous AR and AR-negative 647V/5637 cells stably expressing AR were significantly more resistant to CDDP treatment at its pharmacological concentrations, compared with UMUC3-AR-shRNA and 647V-vector/5637-vector control cells, respectively. A synthetic androgen R1881 significantly reduced CDDP sensitivity in UMUC3, 647V-AR, or 5637-AR cells, and the addition of an anti-androgen hydroxyflutamide inhibited the effect of R1881. In these AR-positive cells, R1881 treatment also induced the expression levels of NF-κB, which is known to involve CDDP resistance, and its phosphorylated form, as well as nuclear translocation of NF-κB. In CDDP-resistant bladder cancer sublines established following long-term culture with CDDP, the expression levels of AR as well as NF-κB and phospho-NF-κB were considerably elevated, compared with respective control sublines. In bladder cancer specimens, there was a strong trend to correlate between AR positivity and chemoresistance. These results suggest that AR activation correlates with CDDP resistance presumably via modulating NF-κB activity in bladder cancer cells. Targeting AR during chemotherapy may thus be a useful strategy to overcome CDDP resistance in patients with AR-positive bladder cancer.

Real time diagnosis of bladder cancer with probe-based confocal laser endomicroscopy

NASA Astrophysics Data System (ADS)

Liu, Jen-Jane; Wu, Katherine; Adams, Winifred; Hsiao, Shelly T.; Mach, Kathleen E.; Beck, Andrew H.; Jensen, Kristin C.; Liao, Joseph C.

2011-02-01

Probe-based confocal laser endomicroscopy (pCLE) is an emerging technology for in vivo optical imaging of the urinary tract. Particularly for bladder cancer, real time optical biopsy of suspected lesions will likely lead to improved management of bladder cancer. With pCLE, micron scale resolution is achieved with sterilizable imaging probes (1.4 or 2.6 mm diameter), which are compatible with standard cystoscopes and resectoscopes. Based on our initial experience to date (n = 66 patients), we have demonstrated the safety profile of intravesical fluorescein administration and established objective diagnostic criteria to differentiate between normal, benign, and neoplastic urothelium. Confocal images of normal bladder showed organized layers of umbrella cells, intermediate cells, and lamina propria. Low grade bladder cancer is characterized by densely packed monomorphic cells with central fibrovascular cores, whereas high grade cancer consists of highly disorganized microarchitecture and pleomorphic cells with indistinct cell borders. Currently, we are conducting a diagnostic accuracy study of pCLE for bladder cancer diagnosis. Patients scheduled to undergo transurethral resection of bladder tumor are recruited. Patients undergo first white light cystocopy (WLC), followed by pCLE, and finally histologic confirmation of the resected tissues. The diagnostic accuracy is determined both in real time by the operative surgeon and offline after additional image processing. Using histology as the standard, the sensitivity, specificity, positive and negative predictive value of WLC and WLC + pCLE are calculated. With additional validation, pCLE may prove to be a valuable adjunct to WLC for real time diagnosis of bladder cancer.

Arsenic in drinking water and urinary tract cancers: a systematic review of 30 years of epidemiological evidence

PubMed Central

2014-01-01

Background Arsenic in drinking water is a public health issue affecting hundreds of millions of people worldwide. This review summarizes 30 years of epidemiological studies on arsenic exposure in drinking water and the risk of bladder or kidney cancer, quantifying these risks using a meta-analytical framework. Methods Forty studies met the selection criteria. Seventeen provided point estimates of arsenic concentrations in drinking water and were used in a meta-analysis of bladder cancer incidence (7 studies) and mortality (10 studies) and kidney cancer mortality (2 studies). Risk estimates for incidence and mortality were analyzed separately using Generalized Linear Models. Predicted risks for bladder cancer incidence were estimated at 10, 50 and 150 μg/L arsenic in drinking water. Bootstrap randomizations were used to assess robustness of effect size. Results Twenty-eight studies observed an association between arsenic in drinking water and bladder cancer. Ten studies showed an association with kidney cancer, although of lower magnitude than that for bladder cancer. The meta-analyses showed the predicted risks for bladder cancer incidence were 2.7 [1.2–4.1]; 4.2 [2.1–6.3] and; 5.8 [2.9–8.7] for drinking water arsenic levels of 10, 50, and 150 μg/L, respectively. Bootstrapped randomizations confirmed this increased risk, but, lowering the effect size to 1.4 [0.35–4.0], 2.3 [0.59–6.4], and 3.1 [0.80–8.9]. The latter suggests that with exposures to 50 μg/L, there was an 83% probability for elevated incidence of bladder cancer; and a 74% probability for elevated mortality. For both bladder and kidney cancers, mortality rates at 150 ug/L were about 30% greater than those at 10 μg/L. Conclusion Arsenic in drinking water is associated with an increased risk of bladder and kidney cancers, although at lower levels (<150 μg/L), there is uncertainty due to the increased likelihood of exposure misclassification at the lower end of the exposure curve. Meta-analyses suggest exposure to 10 μg/L of arsenic in drinking water may double the risk of bladder cancer, or at the very least, increase it by about 40%. With the large number of people exposed to these arsenic concentrations worldwide the public health consequences of arsenic in drinking water are substantial. PMID:24889821

Nitrate in drinking water and risk of death from bladder cancer: an ecological case-control study in Taiwan.

PubMed

Chiu, Hui-Fen; Tsai, Shang-Shyue; Yang, Chun-Yuh

2007-06-01

The relationship between nitrate levels in drinking water and bladder cancer development is controversial. A matched cancer case-control with nitrate ecology study was used to investigate the association between bladder cancer mortality occurrence and nitrate exposure from Taiwan drinking water. All bladder cancer deaths of Taiwan residents from 1999 through 2003 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth,and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on nitrate-nitrogen (NO3-N) levels in drinking water throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was assumed to be the source of the subject's nitrate exposure via drinking water. The adjusted odds ratios for bladder cancer death for those with high nitrate levels in their drinking water were 1.76 (1.28-2.42) and 1.96 (1.41-2.72) as compared to the lowest tertile. The results of the present study show that there was a significant positive relationship between the levels of nitrate in drinking water and risk of death from bladder cancer.

Immune Response Following Photodynamic Therapy For Bladder Cancer

NASA Astrophysics Data System (ADS)

Raymond K.

1989-06-01

This study was undertaken to determine if photodynamic therapy (PDT) produces an immunologic response in patients treated for bladder cancer. Gamma interferon, interleukin 1-beta, interleukin 2 and tumor necrosis factor-alpha were assayed in the urine of four patients treated with photodynamic therapy for bladder cancer, in seven patients undergoing transurethral procedures, and in five healthy control subjects. Quantifiable concentrations of all cytokines, except gamma interferon, were measured in urine samples from the PDT patients treated with the highest light energies, while no urinary cytokines were found in the PDT patient who received the lowest light energy or in the control subjects. These findings suggest that a local immunologic response may occur following PDT for bladder cancer. Such an immunologic response activated by PDT may be an additional mechanism involved in bladder tumor destruction.

Predictive value of Sox2 expression in transurethral resection specimens in patients with T1 bladder cancer.

PubMed

Ruan, Jun; Wei, Bingbing; Xu, Zhuoqun; Yang, Shudong; Zhou, You; Yu, Minhong; Liang, Jiabei; Jin, Ke; Huang, Xing; Lu, Peng; Cheng, Huan

2013-03-01

Sox2 is thought to be an important regulator of self-renewal in embryonic stem cell. According to the cancer stem cell (CSC) theory, the overexpression of Sox2 is potentially involved in carcinogenesis and could affect tumor recurrence and metastasis. Previous study proved Sox2 might be prognostic marker for multiple human malignancies. The purpose of this study was to investigate the clinicopathological significance of Sox2 expression in human non-muscle-invasive bladder cancer. We examined Sox2 expression in 32 paired non-muscle-invasive bladder cancer tissues and adjacent non-cancerous tissues by quantitative real-time RT-PCR (qrtRT-PCR). In addition, we analyzed Sox2 and Ki-67 expression in 126 non-muscle-invasive bladder cancer samples and bladder cancer cell line T24 by immunohistochemistry and immunofluorescence assays. The recurrence-free survival was determined by Kaplan-Meier method and log-rank test. Cox regression was adopted for univariate and multivariate analyses of prognostic factors. The expression of Sox2 was significantly increased in non-muscle-invasive bladder cancer tissues. Sox2 expression was significantly correlated with that of Ki-67 (P < 0.001). The expression of Sox2 was significantly associated with tumor size (P = 0.006), tumor number (P = 0.037), and tumor grade (P < 0.001). Patients with high Sox2 expression had significantly poorer recurrence-free survival (P = 0.0002) when compared with patients with the low expression of Sox2. On multivariate analysis, Sox2 expression and tumor grade were found to be independent prognostic factors for recurrence-free survival (P < 0.05). Our data suggested for the first time that the high expression of Sox2 may contribute to the development of non-muscle-invasive bladder cancer and serve as a novel prognostic marker in patients with T1 bladder cancer.

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

PubMed Central

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

Prediction of mortality after radical cystectomy for bladder cancer by machine learning techniques.

PubMed

Wang, Guanjin; Lam, Kin-Man; Deng, Zhaohong; Choi, Kup-Sze

2015-08-01

Bladder cancer is a common cancer in genitourinary malignancy. For muscle invasive bladder cancer, surgical removal of the bladder, i.e. radical cystectomy, is in general the definitive treatment which, unfortunately, carries significant morbidities and mortalities. Accurate prediction of the mortality of radical cystectomy is therefore needed. Statistical methods have conventionally been used for this purpose, despite the complex interactions of high-dimensional medical data. Machine learning has emerged as a promising technique for handling high-dimensional data, with increasing application in clinical decision support, e.g. cancer prediction and prognosis. Its ability to reveal the hidden nonlinear interactions and interpretable rules between dependent and independent variables is favorable for constructing models of effective generalization performance. In this paper, seven machine learning methods are utilized to predict the 5-year mortality of radical cystectomy, including back-propagation neural network (BPN), radial basis function (RBFN), extreme learning machine (ELM), regularized ELM (RELM), support vector machine (SVM), naive Bayes (NB) classifier and k-nearest neighbour (KNN), on a clinicopathological dataset of 117 patients of the urology unit of a hospital in Hong Kong. The experimental results indicate that RELM achieved the highest average prediction accuracy of 0.8 at a fast learning speed. The research findings demonstrate the potential of applying machine learning techniques to support clinical decision making. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bladder cancers respond to intravesical instillation of HAMLET (human alpha-lactalbumin made lethal to tumor cells).

PubMed

Mossberg, Ann-Kristin; Wullt, Björn; Gustafsson, Lotta; Månsson, Wiking; Ljunggren, Eva; Svanborg, Catharina

2007-09-15

We studied if bladder cancers respond to HAMLET (human alpha-lactalbumin made lethal to tumor cells) to establish if intravesical HAMLET application might be used to selectively remove cancer cells in vivo. Patients with nonmuscle invasive transitional cell carcinomas were included. Nine patients received 5 daily intravesical instillations of HAMLET (25 mg/ml) during the week before scheduled surgery. HAMLET stimulated a rapid increase in the shedding of tumor cells into the urine, daily, during the 5 days of instillation. The effect was specific for HAMLET, as intravesical instillation of NaCl, PBS or native alpha-lactalbumin did not increase cell shedding. Most of the shed cells were dead and an apoptotic response was detected in 6 of 9 patients, using the TUNEL assay. At surgery, morphological changes in the exophytic tumors were documented by endoscopic photography and a reduction in tumor size or change in tumor character was detected in 8 of 9 patients. TUNEL staining was positive in biopsies from the remaining tumor in 4 patients but adjacent healthy tissue showed no evidence of apoptosis and no toxic response. The results suggest that HAMLET exerts a direct and selective effect on bladder cancer tissue in vivo and that local HAMLET administration might be of value in the future treatment of bladder cancers. (c) 2007 Wiley-Liss, Inc.

Atezolizumab With or Without Eribulin Mesylate in Treating Patients With Recurrent Locally Advanced or Metastatic Urothelial Cancer

ClinicalTrials.gov

2018-06-05

Metastatic Urothelial Carcinoma; Recurrent Bladder Urothelial Carcinoma; Recurrent Urethral Urothelial Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Renal Pelvis Urothelial Carcinoma; Stage III Bladder Urothelial Carcinoma AJCC v6 and v7; Stage III Renal Pelvis Cancer AJCC v7; Stage III Ureter Cancer AJCC v7; Stage III Urethral Cancer AJCC v7; Stage IV Bladder Urothelial Carcinoma AJCC v7; Stage IV Renal Pelvis Cancer AJCC v7; Stage IV Ureter Cancer AJCC v7; Stage IV Urethral Cancer AJCC v7; Ureter Urothelial Carcinoma

CDODA-Me decreases specificity protein transcription factors and induces apoptosis in bladder cancer cells through induction of reactive oxygen species.

PubMed

Takeuchi, Hisashi; Taoka, Rikiya; Mmeje, Chinedu O; Jinesh, Goodwin G; Safe, Stephen; Kamat, Ashish M

2016-08-01

The objective is to determine whether methyl 2-cyano-3,11-dioxo-18b-olean-1,12-dien-30-oate (CDODA-Me) has therapeutic potential in bladder cancer. We investigated the effects of CDODA-Me on the growth and survival of bladder cancer cells, and expression of specificity protein (Sp) transcription factors that regulate genes associated with cancer cell proliferation and survival. J82, RT4P, and 253JB-V bladder cancer cell lines were treated with vehicle alone or with CDODA-Me with or without the antioxidant l-glutathione. Cell viability and DNA fragmentation were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and propidium iodide-fluorescence-activated cell sorting (FACS) analysis, respectively. Intracellular reactive oxygen species (ROS) were measured by 2',7'-dichlorofluorescin diacetate-FACS analysis. We assessed CDODA's effects on the levels of Sp and Sp-regulated proteins and induction of apoptosis in bladder cancer cells by Western blotting. We also assessed the anticancer effects of CDODA-Me in nude mice bearing RT4v6 bladder cancer. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and FACS analysis revealed that CDODA-Me inhibited the proliferation and survival of the 3 bladder cancer cell lines in a dose-dependent manner. FACS analysis also indicated that CDODA-Me-induced intracellular ROS, and Western blot analysis indicated that CDODA-Me decreased levels of Sp and Sp-regulated proteins and induced apoptosis in a dose-dependent and time-dependent manner. l-Glutathione attenuated CDODA-Me's down-regulation of Sp and Sp-regulated proteins. Compared with the control treatment, CDODA-Me substantially inhibited tumor growth in vivo. CDODA-Me has antineoplastic activity in bladder cancer cells by inducing ROS, which down-regulate Sp and Sp-regulated proteins. Thus, CDODA-Me has therapeutic potential in bladder cancer, and additional studies of the agent's efficacy and mode of action are warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

Zamora-Ros, R; Sacerdote, C; Ricceri, F; Weiderpass, E; Roswall, N; Buckland, G; St-Jules, D E; Overvad, K; Kyrø, C; Fagherazzi, G; Kvaskoff, M; Severi, G; Chang-Claude, J; Kaaks, R; Nöthlings, 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; Argüelles, M; Amiano, P; Ardanaz, E; Ericson, U; Lindkvist, B; Nilsson, L M; Kiemeney, L A; 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; González, C A

2014-10-28

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 flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases. During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62-0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC. Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC.

Knowledge of the harms of tobacco use among patients with bladder cancer.

PubMed

Bassett, Jeffrey C; Gore, John L; Kwan, Lorna; Ritch, Chad R; Barocas, Daniel A; Penson, David F; McCarthy, William J; Saigal, Christopher S

2014-12-15

The objective of this study was to determine tobacco use knowledge and attribution of cause in patients with newly diagnosed bladder cancer. A stratified, random sample of bladder cancer survivors diagnosed between 2006 and 2009 was obtained from the California Cancer Registry. Respondents were surveyed about tobacco use, risk factors, and sources of information on the causes of bladder cancer. Contingency tables and logistic regression analyses were used to evaluate tobacco use knowledge and beliefs. Of 1198 eligible participants, 790 (66%) completed the survey. Sixty-eight percent of the cohort had a history of tobacco use, and 19% were active smokers at diagnosis. Tobacco use was the most cited risk factor for bladder cancer, with active smokers more knowledgeable than former smokers or never smokers (90% vs 64% vs 61%, respectively; P<.001). Urologists were the predominant source of information and were cited most often by active smokers (82%). In multivariate analyses, active smokers had 6.37 times greater odds (95% confidence interval, 3.35-12.09) than never smokers of endorsing tobacco use as a risk factor for bladder cancer, and smokers who named the urologist as their information source had 2.80 times greater odds (95% confidence interval, 1.77-4.43) of believing tobacco use caused their cancer. Patients' smoking status and primary source of information were associated with knowledge of the harms of tobacco use and, in smokers, acknowledgment that tobacco use increased the risk of their own disease. Urologists play a critical role in ensuring patients' knowledge of the connection between smoking and bladder cancer, particularly for active smokers who may be motivated to quit. © 2014 American Cancer Society.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schooneveldt, G.; Kok, H.P.; Bakker, A.

Purpose: Hyperthermia combined with Mitomycin C is used for the treatment of non-muscle invasive bladder cancer (NMIBC), using a phased array system of microwave antennas for bladder heating. Often some air is present in the bladder, which effectively blocks the microwave radiation, potentially preventing proper treatment of that part of the bladder. Air can be a relevant fraction of the bladder content and large air pockets are expected to have a noticeable influence on achieved temperatures. Methods: We analysed 14 NMIBC patients treated at our institute with our AMC-4 hyperthermia device with four 70MHz antennas around the pelvis. A CTmore » scan was made after treatment and a physician delineated the bladder on the CT scan. On the same scan, the amount of air present in the bladder was delineated. Using our in-house developed hyperthermia treatment planning system, we simulated the treatment using the clinically applied device settings. We did this once with the air pocket delineated on the CT scan, and once with the same volume filled with bladder tissue. Results: The patients had on average 4.2ml (range 0.8–10.1ml) air in the bladder. The bladder volume was delineated by the physician, that is including air pocket and bladder wall, was on average 253ml (range 93–452ml). The average volume in which changes exceeded 0.25°C was 22ml (range 0–108 ml), with the bladder being up to 2°C cooler when an air pocket was present. Except for extreme cases, there was no evident relation between the quantity of air and the difference in temperature. Conclusion: The effect of an air pocket in the bladder during bladder hyperthermia treatment varies strongly between patients. Generally, this leads to lower temperatures in the bladder, potentially affecting treatment quality, and suggesting that care need be taken to minimise the size of air pockets during hyperthermia treatments. The KWF Dutch Cancer Society financially supported this work, grant UVA 2012-5539.« less

Nitrate from Drinking Water and Diet and Bladder Cancer Among Postmenopausal Women in Iowa.

PubMed

Jones, Rena R; Weyer, Peter J; DellaValle, Curt T; Inoue-Choi, Maki; Anderson, Kristin E; Cantor, Kenneth P; Krasner, Stuart; Robien, Kim; Freeman, Laura E Beane; Silverman, Debra T; Ward, Mary H

2016-11-01

Nitrate is a drinking water contaminant arising from agricultural sources, and it is a precursor in the endogenous formation of N-nitroso compounds (NOC), which are possible bladder carcinogens. We investigated the ingestion of nitrate and nitrite from drinking water and diet and bladder cancer risk in women. We identified incident bladder cancers among a cohort of 34,708 postmenopausal women in Iowa (1986-2010). Dietary nitrate and nitrite intakes were estimated from a baseline food frequency questionnaire. Drinking water source and duration were assessed in a 1989 follow-up. For women using public water supplies (PWS) > 10 years (n = 15,577), we estimated average nitrate (NO3-N) and total trihalomethane (TTHM) levels and the number of years exceeding one-half the maximum contaminant level (NO3-N: 5 mg/L, TTHM: 40 μg/mL) from historical monitoring data. We computed hazard ratios (HRs) and 95% confidence intervals (CIs), and assessed nitrate interactions with TTHM and with modifiers of NOC formation (smoking, vitamin C). We identified 258 bladder cancer cases, including 130 among women > 10 years at their PWS. In multivariable-adjusted models, we observed nonsignificant associations among women in the highest versus lowest quartile of average drinking water nitrate concentration (HR = 1.48; 95% CI: 0.92, 2.40; ptrend = 0.11), and we found significant associations among those exposed ≥ 4 years to drinking water with > 5 mg/L NO3-N (HR = 1.62; 95% CI: 1.06, 2.47; ptrend = 0.03) compared with women having 0 years of comparable exposure. TTHM adjustment had little influence on associations, and we observed no modification by vitamin C intake. Relative to a common reference group of never smokers with the lowest nitrate exposures, associations were strongest for current smokers with the highest nitrate exposures (HR = 3.67; 95% CI: 1.43, 9.38 for average water NO3-N and HR = 3.48; 95% CI: 1.20, 10.06 and ≥ 4 years > 5 mg/L, respectively). Dietary nitrate and nitrite intakes were not associated with bladder cancer. Long-term ingestion of elevated nitrate in drinking water was associated with an increased risk of bladder cancer among postmenopausal women. Citation: Jones RR, Weyer PJ, DellaValle CT, Inoue-Choi M, Anderson KE, Cantor KP, Krasner S, Robien K, Beane Freeman LE, Silverman DT, Ward MH. 2016. Nitrate from drinking water and diet and bladder cancer among postmenopausal women in Iowa. Environ Health Perspect 124:1751-1758; http://dx.doi.org/10.1289/EHP191.

Quadruple primary urogenital cancers - A case report.

PubMed

Elec, Florin-Ioan; Zaharie, Andreea; Ene, Bogdan-Mihai; Ghervan, Liviu

2017-01-01

Urogenital cancers are not an uncommon occurrence in daily practice. Prostate cancer is the second most frequent cancer in men, kidney cancer accounts for 2.4% of all cancers and bladder cancers represent 3.1% of cancers in both men and women [1]. However, the cases of a simultaneous development of all three cancers, including one with a neuroendocrine component, are very few and far between. Our case report involves a case of a patient with prostate adenocarcinoma, clear-cell renal carcinoma, papillary renal carcinoma and small-cell bladder cancer. The patient was treated as if he had separate pathologies by a multidisciplinary team: surgical and oncological, performing radical cystoprostatectomy with left perifascial nephroureterectomy, right ureterostomy and adjuvant chemotherapy, with excellent outcome even four years after the initial diagnosis. The distinct features of this case are the occurence of four different malignancies of the urogenital system, the family history of colon cancer, the development of small-cell carcinoma of the bladder, which is extremely rare and the good outcome, despite the quadruple malignancies and the aggresivity of the small-cell carcinoma. Mutiple primary malignancies are a relatively rare pathology, but should be considered as a possibility in patients who already had a second malignancy. Cases of patients with MPMs should be supervised by a multidisciplinary team and should be followed closely. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The diagnostic significance of lactate dehydrogenase isoenzymes in urinary cytology.

PubMed Central

Nishikawa, A.; Tanaka, T.; Takeuchi, T.; Fujihiro, S.; Mori, H.

1991-01-01

Lactate dehydrogenase (LDH) isoenzyme distribution was examined in 106 urine samples being tested cytologically for evidence of bladder cancer; the samples were selected to have less than 20 leucocytes and erythrocytes per high power field and the LDH pattern determined by electrophoresis. The Papanicolaou stained-smears showed 68 negative, 17 suspicious and 21 positive. The LDH M-fraction of the urinary supernatant in cytologically positive cases was significantly greater than in negative cases, although the latter included a few false negative samples. Some of the false negatives gave positive results for the LDH M-fraction; these results suggest that the determination of LDH isoenzymes in the urine is useful in diagnosing urinary tract cancers, including early stage, and for follow-up of patients with bladder cancers after surgical resection. PMID:2039708

[A simple and efficient method for establishing a mouse model of orthotopic MB49 bladder cancer].

PubMed

Liang, Zhong-kun; Zhang, Lin; Hu, Zhi-ming; Chen, Zhong; Huang, Xin; Shi, Xiang-hua; Tan, Wan-long; Gao, Ji-min

2009-04-01

To establish a simple and efficient method for establishing a mouse model of orthotopic superficial bladder cancer. C57BL/6 mice were anesthetized with sodium pentobarbital and catheterized with modified IV catheter (24 G). The mice were intravesically pretreated with HCl and then with NaOH, and after washing the bladders with phosphate-buffered saline (PBS), 100 microl (1 x 10(7)) MB49 cells were infused and allowed to incubate in the bladder for 2 h followed intravesical mitomycin C (MMC) administration. The tumor formation rate, survival, gross hematuria, and bladder weight were determined as the outcome variables, and the pathology of the bladders was observed. Instillation of MB49 tumor cells resulted in a tumor formation rates of 100% in all the pretreated groups while 0% in the control group without pretreatment. MMC significantly reduced the bladder weight as compared to PBS. We have successfully established a stable, reproducible, and reliable orthotopic bladder cancer model in mice.

Renin-Angiotensin Inhibitors Decrease Recurrence after Transurethral Resection of Bladder Tumor in Patients with Nonmuscle Invasive Bladder Cancer.

PubMed

Blute, Michael L; Rushmer, Timothy J; Shi, Fangfang; Fuller, Benjamin J; Abel, E Jason; Jarrard, David F; Downs, Tracy M

2015-11-01

Prior reports suggest that renin-angiotensin system inhibition may decrease nonmuscle invasive bladder cancer recurrence. We evaluated whether angiotensin converting enzyme inhibitor or angiotensin receptor blocker treatment at initial surgery was associated with decreased recurrence or progression in patients with nonmuscle invasive bladder cancer. Using an institutional bladder cancer database we identified 340 patients with data available on initial transurethral resection of bladder tumor. Progression was defined as an increase to stage T2. Cox proportional hazards models were used to evaluate associations with recurrence-free and progression-free survival. Median patient age was 69.6 years. During a median followup of 3 years (IQR 1.3-6.1) 200 patients (59%) had recurrence and 14 (4.1%) had stage progression. Of those patients 143 were receiving angiotensin converting enzyme inhibitor/angiotensin receptor blockers at the time of the first transurethral resection. On univariate analysis factors associated with improved recurrence-free survival included carcinoma in situ (p = 0.040), bacillus Calmette-Guérin therapy (p = 0.003) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (p = 0.009). Multivariate analysis demonstrated that patients treated with bacillus Calmette-Guérin therapy (HR 0.68, 95% CI 0.47-0.87, p = 0.002) or angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (HR 0.61, 95% CI 0.45-0.84, p = 0.005) were less likely to experience tumor recurrence. The 5-year recurrence-free survival rate was 45.6% for patients treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers and 28.1% in those not treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers (p = 0.009). Subgroup analysis was performed to evaluate nonmuscle invasive bladder cancer pathology (Ta, T1 and carcinoma in situ) in 85 patients on bacillus Calmette-Guérin therapy alone and in 52 in whom it was combined with angiotensin converting enzyme inhibitor/angiotensin receptor blocker. Multivariate analysis revealed that patients treated with bacillus Calmette-Guérin alone (HR 2.19, 95% CI 1.01-4.77, p = 0.04) showed worse recurrence-free survival compared to patients treated with bacillus Calmette-Guérin and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (stage Ta HR 0.45, 95% CI 0.21-0.98, p = 0.04). Pharmacological inhibition of the renin-angiotensin system is associated with improved outcomes in patients with bladder cancer. Renin-angiotensin system inhibitor administration in nonmuscle invasive bladder cancer cases should be studied in a prospective randomized trial. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Pattern of somatostatin receptors expression in normal and bladder cancer tissue samples.

PubMed

Karavitakis, Markos; Msaouel, Pavlos; Michalopoulos, Vassilis; Koutsilieris, Michael

2014-06-01

Known risks factors for bladder cancer progression and recurrence are limited regarding their prognostic ability. Therefore identification of molecular determinants of disease progression could provide with more specific prognostic information and could be translated into new approaches for biomarker development. In the present study we evaluated, the expression patterns of somatostatin receptors 1-5 (SSTRs) in normal and tumor bladder tissues. The expression of SSTR1-5 was characterized in 45 normal and bladder cancer tissue samples using reverse transcriptase-polymerase chain reaction (RT-PCR). SSTR1 was expressed in 24 samples, SSTR2 in 15, SSTR3 in 23, SSTR4 in 16 and SSTR5 in all but one sample. Bladder cancer tissue samples expressed lower levels of SSTR3. Co-expression of SSTRs was associated with superficial disease. Our results demonstrate, for the first time, that there is expression of SSTR in normal and bladder cancer urothelium. Further studies are required to evaluate the prognostic and therapeutic significance of these findings. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Unusual asymptomatic presentation of bladder cancer metastatic to the penis.

PubMed

Giunchi, Francesca; Vasuri, Francesco; Valerio, Vagnoni; Montagnani, Ilaria; Nelli, Federico; Fiorentino, Michelangelo; Raspollini, Maria Rosaria

2017-06-01

Penile metastasis is an extremely rare event and mainly originate from primary pelvic tumor sites such us urinary bladder, gastro-intestinal tract and prostate and more rarely from respiratory system, bone tumors and melanoma. Here we describe the unusual presentation of two bladder urothelial cancer metastatic to the penis with no relevant clinical symptoms. Namely, a 69 years-old man with a warthy lesions of the foreskin and the glans misunderstood for a condylomata that at histological and immunohistochemical analysis showed a bladder urothelial carcinoma; and a 71 years-old man with reddish skin lesion of the glans, a previous history of bladder and urethral carcinoma and histological pagetoid spread of urothelial cancer to the glans. Recurrent bladder urothelial carcinoma is usually a visceral disease that rarely presents as a superficial asymptomatic skin lesion. The two reported cases were asymptomatic superficial penis metastases with a relatively slow growth and a fairy good prognosis after conservative surgical approach. Accurate clinical examination of the penis is mandatory for males with history of bladder cancer. Copyright © 2016 Elsevier GmbH. All rights reserved.

The clinical use of neutrophil-to-lymphocyte ratio in bladder cancer patients: a systematic review and meta-analysis.

PubMed

Tang, Xingxing; Du, Peng; Yang, Yong

2017-10-01

The aim of this study was to evaluate the evidence regarding the neutrophil-to-lymphocyte ratio (NLR) as a factor predictive of survival in bladder cancer patients. A search of PubMed and Embase for relevant studies between January 1, 1966 and November 10, 2016 was performed with the terms [NLR OR (neutrophil lymphocyte ratio)] AND [(bladder cancer) OR BCa OR NMIBC OR MIBC]. Inclusion required studies published in English containing bladder cancer patients and evaluating NLR as a predictive factor. Endpoints of NLR and survival data were extracted for pooled analysis. The pooled results showed that an elevated NLR was a predictor for poor overall survival (OS) [hazard ratio (HR) = 1.19, 95% confidence interval (CI) 1.07-1.31], cancer-specific survival (CSS) (HR = 1.40, 95% CI 1.17-1.69), recurrence-free survival (RFS) (HR = 1.58, 95% CI 1.24-2.03) and progression-free survival (PFS) (HR = 1.33, 95% CI 1.19-1.49) in patients with bladder cancer. Heterogeneity between studies was observed for OS, CSS and RFS, but not for PFS. Publication bias was detected for all these outcomes. Our results showed that elevated NLR might be valuable as a predictive factor of survival in bladder cancer patients.

An analysis of suppressing migratory effect on human urinary bladder cancer cell line by silencing of snail-1.

PubMed

Salehi, Shima; Mansoori, Behzad; Mohammadi, Ali; Davoudian, Sadaf; Musavi Shenas, Seyed Mohammad Hossein; Shajari, Neda; Majidi, Jafar; Baradaran, Behzad

2017-12-01

Snail-1 actively participates in tumor progression, invasion, and migration. Targeting snail-1 expression can suppress the EMT process in cancer. The aim of this study was to investigate the effect of snail1 silencing on urinary bladder cancer. Quantitative RT-PCR was used to detect snail-1 and other related metastatic genes expression following siRNA knockdown in urinary bladder cancer EJ-138 cells. The protein level of snail1 was assessed by Western blot. MTT and TUNEL assays were assessed to understand if snail-1 had survival effects on EJ-138 cells. Scratch wound healing assay measured cell motility effects after snail1 suppression. The significant silencing of snail-1 reached 60pmol siRNA in a 48-h post-transfection. The result of scratch assay showed that snail-1 silencing significantly decreased Vimentin, MMPs, and CXCR4 expression; however, expression of E-cadherin was induced. The cell death assay indicated that snail-1 played the crucial role in bladder cancer survival rate. These results propose that snail-1 plays a major role in the progression and migration of urinary bladder cancer, and can be a potential therapeutic target for target therapy of invasive urinary bladder cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Non-alcoholic beverages and risk of bladder cancer in Uruguay

PubMed Central

De Stefani, Eduardo; Boffetta, Paolo; Deneo-Pellegrini, Hugo; Correa, Pelayo; Ronco, Alvaro L; Brennan, Paul; Ferro, Gilles; Acosta, Giselle; Mendilaharsu, María

2007-01-01

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. PMID:17394632

CXCL5 knockdown expression inhibits human bladder cancer T24 cells proliferation and migration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Jiajia; Zhu, Xi; Zhang, Jie, E-mail: zhangjiebjmu@163.com

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 PCRmore » 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.« less

[Tumor markers for bladder cancer: up-to-date study by the Kiel Tumor Bank].

PubMed

Hautmann, S; Eggers, J; Meyhoff, H; Melchior, D; Munk, A; Hamann, M; Naumann, M; Braun, P M; Jünemann, K P

2007-11-01

The number of noninvasive diagnostic tests for bladder cancer has increased tremendously over the last years with a large number of experimental and commercial tests. Comparative analyses of tests for diagnosis, follow-up, and recurrence detection of bladder cancer were performed retrospectively as well as prospectively, unicentrically, and multicentrically. An analysis of multicentric studies with large patient numbers compared with our own Kiel Tumor Bank data is presented. The Kiel Tumor Bank data looked prospectively at 106 consecutive bladder tumor patients from the year 2006. Special focus was put on urine cytology as a reference test, as well as the commercial NMP 22 Bladder Chek. The analysis of the NMP 22 Bladder Chek showed an overall sensitivity of 69% for all tumor grades and stages, with a specificity of 76%. Comparison to multicentric data with an overall sensitivity of 75% for all tumor grades and stages, with a specificity of 73%, showed results similar to those in the literature. Urine cytology showed a comparable overall sensitivity of 73% for all tumor grades and stages, with a specificity of 80%. A large number of noninvasive tests for bladder cancer follow-up with reasonable sensitivity and specificity can currently be used. Because of limited numbers of prospective randomized multicentric studies, no single particular marker for bladder cancer screening can be recommended at this point in time.

NCCN Guidelines® Insights Bladder Cancer, Version 2.2016 Featured Updates to the NCCN Guidelines

PubMed Central

Clark, Peter E.; Spiess, Philippe E.; Agarwal, Neeraj; Bangs, Rick; Boorjian, Stephen A.; Buyyounouski, Mark K.; Efstathiou, Jason A.; Flaig, Thomas W.; Friedlander, Terence; Greenberg, Richard E.; Guru, Khurshid A.; Hahn, Noah; Herr, Harry W.; Hoimes, Christopher; Inman, Brant A.; Kader, A. Karim; Kibel, Adam S.; Kuzel, Timothy M.; Lele, Subodh M.; Meeks, Joshua J.; Michalski, Jeff; Montgomery, Jeffrey S.; Pagliaro, Lance C.; Pal, Sumanta K.; Patterson, Anthony; Petrylak, Daniel; Plimack, Elizabeth R.; Pohar, Kamal S.; Porter, Michael P.; Sexton, Wade J.; Siefker-Radtke, Arlene O.; Sonpavde, Guru; Tward, Jonathan; Wile, Geoffrey; Dwyer, Mary A.; Smith, Courtney

2017-01-01

These NCCN Guidelines Insights discuss the major recent updates to the NCCN Guidelines for Bladder Cancer based on the review of the evidence in conjunction with the expert opinion of the panel. Recent updates include (1) refining the recommendation of intravesical bacillus Calmette-Guérin, (2) strengthening the recommendations for perioperative systemic chemotherapy, and (3) incorporating immunotherapy into second-line therapy for locally advanced or metastatic disease. These NCCN Guidelines Insights further discuss factors that affect integration of these recommendations into clinical practice. PMID:27697976

Inhibition of long non-coding RNA UCA1 by CRISPR/Cas9 attenuated malignant phenotypes of bladder cancer.

PubMed

Zhen, Shuai; Hua, Ling; Liu, Yun-Hui; Sun, Xiao-Min; Jiang, Meng-Meng; Chen, Wei; Zhao, Le; Li, Xu

2017-02-07

CRISPR/Cas9 is a novel and effective genome editing technique, but its application is not widely expanded to manipulate long non-coding RNA (lncRNA) expression. The lncRNA urothelial carcinoma-associated 1 (UCA1) is upregulated in bladder cancer and promotes the progression of bladder cancer. Here, we design gRNAs specific to UCA1 and construct CRISPR/Cas9 systems targeting UCA1. Single CRISPR/Cas9-UCA1 can effectively inhibit UCA1 expression when transfected into 5637 and T24 bladder cancer cells, while the combined transfection of the two most effective CRISPR/Cas9-UCA1s can generate more satisfied inhibitory effect. CRISPR/Cas9-UCA1s attenuate UCA1 expression via targeted genome-specific DNA cleavage, resulting in the significant inhibition of cell proliferation, migration and invasion in vitro and in vivo. The mechanisms associated with the inhibitory effect of CRISPR/Cas9-UCA1 on malignant phenotypes of bladder cancer are attributed to the induction of cell cycle arrest at G1 phase, a substantial increase of apoptosis, and an enhanced activity of MMPs. Additionally, urinary UCA1 can be used as a non-invasive diagnostic marker for bladder cancer as revealed by a meta-analysis. Collectively, our data suggest that CRISPR/Cas9 technique can be used to down-modulate lncRNA expression, and urinary UCA1 may be used as a non-invasive marker for diagnosis of bladder cancer.

Clinical significance and biological roles of CARMA3 in human bladder carcinoma.

PubMed

Man, Xiaojun; He, Jiani; Kong, Chuize; Zhu, Yuyan; Zhang, Zhe

2014-05-01

Caspase recruitment domain and membrane-associated guanylate kinase-like domain protein 3 (CARMA3) was reported as an oncoprotein overexpressed in several cancers. The expression pattern of CARMA3 and its clinical significance in human bladder cancer have not been well characterized. In the present study, CARMA3 expression was analyzed in 90 archived bladder cancer specimens using immunohistochemistry, and the correlation between CARMA3 expression and clinicopathological parameters was evaluated. We found that CARMA3 was overexpressed in 35 of 90 (38.8%) bladder cancer specimens. Significant association was observed between CARMA3 overexpression with tumor status (p = 0.081) and tumor grade (p = 0.027). To further explore the biological functions of CARMA3 in bladder cancer, we depleted CARMA3 in T24 and 5637 cell lines using small interfering RNA (siRNA). Using cell counting kit-8 (CCK8) assay and colony formation assay, we were able to show that CARMA3 depletion inhibited cell proliferation and colony number. Further study demonstrated that CARMA3 depletion decreased an expression of nuclear factor kappa B (NF-κB) targets cyclin D1 and Bcl-2 expression, as well as IκB phosphorylation. Luciferase reporter assay showed that CARMA3 depletion could downregulate NF-κB reporter activity. In conclusion, CARMA3 is overexpressed in bladder cancer and regulates malignant cell growth and NF-κB signaling, which makes CARMA3 a candidate therapeutic target for bladder cancer.

[Primary upper urinary tract tumors and subsequent location in the bladder].

PubMed

Azémar, M-D; Audouin, M; Revaux, A; Misraï, V; Comperat, E; Bitker, M-O; Chartier-Kastler, E; Richard, F; Cussenot, O; Rouprêt, M

2009-10-01

The urothelium is the epithelium that lines the upper and lower urinary tract. Over 95% of urothelial carcinomas are derived from urothelium. They can be located in the lower tract (bladder, urethra) or upper tract (pyelocaliceal cavities, ureter). Urothelial carcinomas are the fourth most common tumours after prostate (or breast) cancer, lung cancer and colorectal cancer. On one hand, bladder tumours account for 90-95% of urothelial carcinomas. It is the most common malignancy of the urinary tract and the second most common malignancy of the urogenital tract after prostate cancer. It accounts for 5-10% of all cancers diagnosed each year in Europe. On the other hand, upper urinary tract urothelial cell carcinomas (UUT-UCC) are scarce and account for only 5-10% of urothelial carcinomas. Recurrence in the bladder after primary UUT-UCC occurs in 15-50% of UUT-UCC. Differences in treatment modalities of the primary UUT-UCC do not play a key role in the subsequent appearance of a bladder recurrence. However, others factors have been described such as stage and location in the upper tract of the primary tumour or upper tract tumour multifocality. Previous history of bladder tumour is also associated with the risk that another tumour arises in the bladder subsequently. However, it becomes difficult to distinguish between natural history of bladder tumour and evolution of UUT-UCC in these cases. In most cases, bladder cancer occurs in the first two years after UUT-UCC management. Surveillance protocol is based on cystoscopy and on urinary cytology during at least every three months for two years. Current surveillance regimen have a low level of evidence considering the paucity of UUT-UCC.

Occupation and bladder cancer: a population-based, case-control study in Iowa.

PubMed

Zheng, Tongzhang; Cantor, Kenneth P; Zhang, Yawei; Lynch, Charles F

2002-07-01

While considerable efforts have been made to investigate the role of occupation and industry in the risk of bladder cancer, many reported associations have not been consistent, and strong evidence of increased risk is apparent for few occupational groups. To further examine the issue, a large, population-based, case-control study was conducted in the state of Iowa among both men and women. A total of 1452 incident bladder cancer cases and 2434 controls were included in the study. Occupational history was collected from respondents for each job held for 5 years or longer since age 16. Among men, excess risk was observed for industries including plumbing, heating, and air conditioning (odds ratio [OR], = 2.2; 95% confidence interval [CI], 1.0 to 5.0); rubber and plastic products (OR = 3.1; 95% CI, 1.2 to 8.5), motor vehicle parts and supplies (OR = 4.5; 95% CI, 1.2 to 16.5), and occupations including supervisors for transportation and material moving (OR = 6.5; 95% CI, 1.4 to 29.9), material-moving-equipment operators (OR = 1.9; 95% CI, 1.0 to 3.6), automobile mechanics (OR = 1.6; 95% CI, 1.0 to 2.6), painters (OR = 2.7; 95% CI, 1.0 to 7.7), and metal- and plastic-working machine operators (OR = 2.0; 95% CI, 1.1 to 3.4). Among women, significant excess risk was observed for secondary school teachers and record clerks. Housekeepers and butlers and workers in laundering and dry cleaning were also at increased risk. In conclusion, these results suggest that occupational exposures may play a significant role in the risk of bladder cancer.

Enhanced Application of 18F-FDG PET/CT in Bladder Cancer by Adding Early Dynamic Acquisition to a Standard Delayed PET Protocol.

PubMed

Yoon, Hai-Jeon; Yoo, Jang; Kim, Yemi; Lee, Dong Hyeon; Kim, Bom Sahn

2017-10-01

We investigated the value of early dynamic (ED) PET for the detection and characterization of bladder cancer. Fifty-two bladder cancer patients were prospectively enrolled. The study protocol was composed of ED, whole-body (WB, 60 minutes after injection), and additional delayed (AD, 120 minutes after injection) PET acquisition. Early dynamic PET was acquired for 10 minutes and reconstructed as 5 frames at 2-minute intervals. A focal radiotracer accumulation confined to the bladder wall was considered as PET positive and referred for further quantitative measurement. SUVmax on ED (SUVmax, SUVmax, SUVmax, SUVmax, and SUVmax for 5 frames), WB (SUVmax), and AD PET (SUVmax) were measured. PET results were correlated with bladder cancer pathology variables. The sensitivities of ED, WB, and AD PET for bladder cancer were 84.6%, 57.7%, and 61.2%, respectively. The sensitivity of ED PET was significantly higher than that of WB (P = 0.002) and AD PET (P = 0.008). On ED PET, SUVmax was significantly correlated with muscle invasiveness, histological grade, and pathological tumor size (P = 0.018, P = 0.030, and P = 0.030). On WB and AD PET, only pathological tumor size showed significant positive correlation with SUVmax and SUVmax (P = 0.043 and P = 0.007). Early dynamic PET can help to detect and characterize bladder cancer.

SU-F-BRD-01: A Logistic Regression Model to Predict Objective Function Weights in Prostate Cancer IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boutilier, J; Chan, T; Lee, T

2014-06-15

Purpose: To develop a statistical model that predicts optimization objective function weights from patient geometry for intensity-modulation radiotherapy (IMRT) of prostate cancer. Methods: A previously developed inverse optimization method (IOM) is applied retrospectively to determine optimal weights for 51 treated patients. We use an overlap volume ratio (OVR) of bladder and rectum for different PTV expansions in order to quantify patient geometry in explanatory variables. Using the optimal weights as ground truth, we develop and train a logistic regression (LR) model to predict the rectum weight and thus the bladder weight. Post hoc, we fix the weights of the leftmore » femoral head, right femoral head, and an artificial structure that encourages conformity to the population average while normalizing the bladder and rectum weights accordingly. The population average of objective function weights is used for comparison. Results: The OVR at 0.7cm was found to be the most predictive of the rectum weights. The LR model performance is statistically significant when compared to the population average over a range of clinical metrics including bladder/rectum V53Gy, bladder/rectum V70Gy, and mean voxel dose to the bladder, rectum, CTV, and PTV. On average, the LR model predicted bladder and rectum weights that are both 63% closer to the optimal weights compared to the population average. The treatment plans resulting from the LR weights have, on average, a rectum V70Gy that is 35% closer to the clinical plan and a bladder V70Gy that is 43% closer. Similar results are seen for bladder V54Gy and rectum V54Gy. Conclusion: Statistical modelling from patient anatomy can be used to determine objective function weights in IMRT for prostate cancer. Our method allows the treatment planners to begin the personalization process from an informed starting point, which may lead to more consistent clinical plans and reduce overall planning time.« less

Antitumor potential of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H-pyrazoles in human bladder cancer cells.

PubMed

Tessmann, Josiane Weber; Buss, Julieti; Begnini, Karine Rech; Berneira, Lucas Moraes; Paula, Favero Reisdorfer; de Pereira, Claudio Martin Pereira; Collares, Tiago; Seixas, Fabiana Kömmling

2017-10-01

Bladder cancer is a genitourinary malignant disease common worldwide. Current chemotherapy is often limited mainly due to toxicity and drug resistance. Thus, there is a continued need to discover new therapies. Recently evidences shows that pyrazoline derivatives are promising antitumor agents in many types of cancers, but there are no studies with bladder cancer. In order to find potent and novel chemotherapy drugs for bladder cancer, a series of pyrazoline derivatives 2a-2d were tested for their antitumor activity in two human bladder cancer cell lines 5647 and T24. The MTT assay showed that the compounds 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-1H-pyrazole (2a) and 1-thiocarbamoyl-5-(4-chlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazole (2c) decrease the cell viability of 5637 cells. Molecular modeling indicated that these compounds had a good oral bioavailability and low toxicities. Clonogenic assay and flow cytometric analysis were used to assess colony formation, apoptosis induction and cell cycle distribution. Overall, our results suggest that pyrazoline 2a and 2c, with the substituents hydrogen and chlorine respectively, may decrease cell viability and colony formation of bladder cancer 5637 cell line by inhibition of cell cycle progression, and for pyrazoline 2a, by induction of apoptosis. As indicated by the physicochemical properties of these compounds, the steric factor influences the activity. Therefore, these pyrazoline derivatives can be considered promising anticancer agents for the treatment of bladder cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Diffusion and localization of hematoporphyrin derivative in the normal bladder wall of pig and rat after local administration

NASA Astrophysics Data System (ADS)

Bisson, Jean F.; Notter, Dominique; Labrude, P.; Vigneron, C.; Guillemin, Francois H.

1996-01-01

Photodynamic therapy (PDT) consists in the administration of a photosensitizer and subsequent irradiation of the tumor with visible light. Routinely, the photosensitizer is given intravenously (i.v.), but the major drawback of this procedure is the resulting skin photosensitivity. The goal of our study was to examine whether intravesical (i.b.) instillation of the photosensitizer for PDT of bladder cancer might be feasible in order to target the tumors and to avoid the photosensitization phenomenon. After studying the normal bladder histology of pig and rat, not much described so far, we studied the diffusion and localization of hematoporphyrin derivative (HpD) in vitro on the pig bladder and the biodistribution of HpD in vivo in the rat bladder, two and four hours after intravesical administration, by spectrofluorimetry and fluorescence microscopy. We have the following results: (1) no diffusion through the pig bladder wall was detected; (2) the penetration depth of HpD into the pig bladder wall was 450 plus or minus 44 micrometers (n equals 8), including urothelium and chorion in totality and a small part of the muscles; (3) the penetration depth of HpD into the rat bladder wall was 55 plus or minus 9 micrometer (n equals 9) after two hours and 960 plus or minus 118 micrometer (n equals 9) after four hours, corresponding respectively to the totality of the urothelium and a small part of the chorion or almost completely in the bladder wall, a small part of the adventicia being excluded. In conclusion, intravesical instillation is feasible and, as superficial bladder cancer, especially carcinoma in situ particularly occur in the urothelium or in the chorion, a bladder instillation of two hours should be advantageous.

Interleukin-4 receptor alpha overexpression in human bladder cancer correlates with the pathological grade and stage of the disease.

PubMed

Joshi, Bharat H; Leland, Pamela; Lababidi, Samir; Varrichio, Frederick; Puri, Raj K

2014-12-01

Previously, we have demonstrated that interleukin-4 receptor α (IL-4Rα) is overexpressed on a variety of human cancers and can serve as target for IL-4 immunotoxin comprised of IL-4 and a mutated Pseudomonas exotoxin. However, its expression and association with grade and clinical stage of bladder cancer has not been studied. IL-4Rα expression was examined in human bladder cancer cell lines, mouse xenografts, and biopsy specimens at mRNA and protein levels by real-time RT-PCR and IHC/ISH techniques. We also examined the effect of IL-4 on proliferation and invasion of bladder carcinoma cell lines. For tissue microarray (TMA) results, we analyzed the precision data using exact binomial proportion with exact two-sided P-values. We used Cochran-Armitage Statistics with exact two-sided P-values to examine the trend analysis of IL-4Rα over grade or stage of the bladder cancer specimens. The influence of age and gender covariates was also analyzed using multiple logistic regression models. IL-4Rα is overexpressed in five bladder cancer cell lines, while normal bladder and human umbilical vein cell lines (HUVEC) expressed at low levels. Two other chains of IL-4 receptor complex, IL-2RγC and IL-13Rα1, were absent or weakly expressed. IL-4 modestly inhibited the cell proliferation, but enhanced cell invasion of bladder cancer cell lines in a concentration-dependent manner. Bladder cancer xenografts in immunodeficient mice also maintained IL-4Rα overexpression in vivo. Analysis of tumor biopsy specimens in TMAs revealed significantly higher IL-4Rα immunostaining (≥ 2+) in Grade 2 (85%) and Grade 3 (97%) compared to Grade 1 tumors (0%) (P ≤ 0.0001). Similarly, 9% stage I tumors were positive for IL-4Rα (≥ 2+) compared to 84% stage II (P ≤ 0.0001) and 100% stages III-IV tumors (P ≤ 0.0001). IL-13Rα1 was also expressed in tumor tissues but at low levels and it did not show any correlation with the grade and stage of disease. However, the IL-2RγC was not expressed. Ten normal bladder specimens demonstrated ≤ 1+ staining for IL-4Rα and IL-13Rα1 and no staining for IL-2RγC. These results demonstrate that IL-4Rα is overexpressed in human bladder cancer, which correlates with advanced grade and stage of the disease. Thus, IL-4Rα may be a bladder tumor-associated protein and a prognostic biomarker. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Cancer Medicine published by John Wiley & Sons Ltd.

Curcumin inhibits bladder cancer stem cells by suppressing Sonic Hedgehog pathway.

PubMed

Wang, Dengdian; Kong, Xiaochuan; Li, Yuan; Qian, Weiwei; Ma, Jiaxing; Wang, Daming; Yu, Dexin; Zhong, Caiyun

2017-11-04

Cancer stem cells (CSCs) is responsible for the recurrence of human cancers. Thus, targeting CSCs is considered to be a valid way for human cancer treatment. Curcumin is a major component of phytochemicals that exerts potent anticancer activities. However, the effect of curcumin on bladder cancer stem cells (BCSCs) remains to be elucidated. In this study, we investigated the mechanism of curcumin suppressing bladder cancer stem cells. In this study, UM-UC-3 and EJ cells were cultured in serum-free medium (SFM) to form cell spheres that was characterized as BCSCs. Then cell spheres were separately treated with different concentrations of curcumin and purmorphamine. Cell cycle analysis were used to determine the percentage of cells in different phases. Western blot and quantitative real-time PCR analysis were used to detect the expression of relative molecules. Immunofluorescence staining analysis were also utilized to measure the protein level of CD44. We found that CSC markers, including CD44, CD133, ALDH1-A1, OCT-4 and Nanog, were obviously highly expressed in cell spheres. Moreover, we observed that curcumin reduced the cell spheres formation, decreased the expression of CSC markers, suppressed cell proliferation and induced cell apoptosis. We also found that curcumin inhibited the activation of Shh pathway, while the inhibitory effects of curcumin on BCSCs could be weakened by upregulation of Sonic Hedgehog (Shh) pathway. Altogether, these data suggested that curcumin inhibited the activities of BCSCs through suppressing Shh pathway, which might be an effective chemopreventive agent for bladder cancer intervention. Copyright © 2017. Published by Elsevier Inc.

Intravesical antineoplastic therapy following transurethral resection of bladder tumors: nursing implications from the operating room to discharge.

PubMed

Washburn, Donna J

2007-08-01

An aging population and latent effects from exposure to carcinogens will likely augment the current trend of increased incidence of urinary bladder cancer. Intravesical antineoplastic therapy is a common treatment for urinary bladder cancer. Transurethral resection of bladder tumors often is followed immediately by the instillation of an antineoplastic agent in the operating room or postanesthesia care unit. Oncology nurses, who have a unique knowledge of safe handling and patient care, can improve staff safety and patient outcomes in several areas of healthcare organizations, as well as reduce the mortality and morbidity of urinary bladder cancer by learning more about the disease and intravesical antineoplastic therapy.

[The role of telomerase activity in non-invasive diagnostics of bladder cancer].

PubMed

Glybochko, P V; Alyaev, J G; Potoldykova, N V; Polyakovsky, K A; Vinarov, A Z; Glukhov, A I; Gordeev, S A

2016-08-01

To evaluate the potentials of determining the telomerase activity (TA) in the cellular material of the urine for noninvasive diagnosis of bladder cancer (BC). Evaluation of TA was performed in the urine of 48 patients with bladder cancer (study group) before and after transurethral resection of the bladder wall (n=38), an open resection of the bladder (n=4), and cystectomy (n=6). TA was also evaluated in 48 tumor tissue samples obtained from these patients during removal of the bladder tumor. Each sample of the tumor tissue was separated into two parts, one of which was subjected to histological examination, and the latter was used to determine the telomerase activity. In all cases, the diagnosis of bladder cancer was confirmed morphologically. Determination of TA in the samples was performed by the modified TRAP-method (telomerase repeat amplification protocol), RT-PCR, PCR, and electrophoresis. As a control, cell material of the urine and tissue in 12 patients with chronic cystitis was investigated. TA before surgery was found in 45 (93.75%) of 48 samples of cellular material of the urine from patients with suspected bladder cancer. BC was histologically verified in all patients in this group. In the postoperative period, TA was not observed in the 48 samples of cellular material of the urine from patients with BC. In the control group of patients with histologically verified cystitis, weak TA was determined only in one sample of cellular material of the urine. The analysis indicates statistically significant predominance of patients with bladder cancer in case of TA in the urine (P=0.001). TA was detected in all samples of tumor tissue. We also analyzed the dependence of TA levels in urine and tissue on the degree of BC differentiation. In patients with highly differentiated BC, mean AT in the cellular materials of the urine was 0,61% (n=15), in patients with moderately differentiated BC - 0.95% (n=23), in patients with low-grade bladder cancer - 1.33% (n=10); in other words, increase in the TA levels with decreasing the degree of differentiation was observed. This finding can be used in the prognosis of the course of disease based on determining the TA level in these patients. Preliminary data indicate the possibility of use of determining the TA in cellular material of the urine for the diagnosis and monitoring of bladder cancer recurrence.

COMPREHENSIVE ANALYSES OF DNA REPAIR PATHWAYS, SMOKING, AND BLADDER CANCER RISK IN LOS ANGELES AND SHANGHAI

PubMed Central

Corral, Roman; Lewinger, Juan Pablo; Berg, David Van Den; Joshi, Amit D.; Yuan, Jian-Min; Gago-Dominguez, Manuela; Cortessis, Victoria K.; Pike, Malcolm C.; Conti, David V.; Thomas, Duncan C.; Edlund, Christopher K.; Gao, Yu-Tang; Xiang, Yong-Bing; Zhang, Wei; Su, Yu-Chen; Stern, Mariana C.

2014-01-01

Tobacco smoking is a bladder cancer risk factor and a source of carcinogens that induce DNA damage to urothelial cells. Using data and samples from 988 cases and 1,004 controls enrolled in the Los Angeles County Bladder Cancer Study and the Shanghai Bladder Cancer Study we investigated associations between bladder cancer risk and 632 tagSNPs that comprehensively capture genetic variation in 28 DNA repair genes from four DNA repair pathways: base excision repai, nucleotide excision repair (NER), non-homologous end-joining (NHEJ), and homologous recombination repair (HHR). Odds ratios (ORs) and 95% confidence intervals (CIs) for each tagSNP were corrected for multiple testing for all SNPs within each gene using pACT, and for genes within each pathway and across pathways with Bonferroni. Gene and pathway summary estimates were obtained using ARTP. We observed an association between bladder cancer and POLB rs7832529 (BER) (pACT = 0.003; ppathway = 0.021) among all, and SNPs in XPC (NER) and OGG1 (BER) among Chinese men and women, respectively. The NER pathway showed an overall association with risk among Chinese males (ARTP NER p = 0.034). The XRCC6 SNP rs2284082 (NHEJ), also in LD with SREBF2, showed an interaction with smoking (Smoking status interaction pgene = 0.001, ppathway = 0.008, poverall = 0.034). Our findings support a role in bladder carcinogenesis for regions that map close to or within BER (POLB, OGG1) and NER genes (XPC). A SNP that tags both the XRCC6 and SREBF2 genes strongly modifies the association between bladder cancer risk and smoking. PMID:24382701

Genetic determinants in the metabolism of bladder carcinogens in relation to risk of bladder cancer

PubMed Central

Yuan, Jian-Min; Chan, Kenneth K.; Coetzee, Gerhard A.; Castelao, J.Esteban; Watson, Mary A.; Bell, Douglas A.; Wang, Renwei; Yu, Mimi C.

2008-01-01

Genetically determined factors that alter the metabolism of tobacco carcinogens can influence an individual’s susceptibility to bladder cancer. The associations between the genotypes of glutathione S-transferase (GST) M1, GSTP1, GSTT1 and N-acetyltransferase (NAT) 1 and the phenotypes of NAT2 and cytochrome P450 (CYP) 1A2 and bladder cancer risk were examined in a case–control study involving 731 bladder cancer patients and 740 control subjects in Los Angeles County, California. Individual null/low-activity genotypes of GSTM1, GSTT1 and GSTP1 were associated with a 19–48% increase in odds ratio (OR) of bladder cancer. The strongest association was noted for GSTM1 [OR for the null genotype = 1.48, 95% confidence interval (CI) = 1.19–1.83]. When the three GST genes were examined together, there was a monotonic, statistically significant association between increasing number of null/low-activity genotypes and risk (P for trend = 0.002). OR (95% CI) for one and two or more null/low-activity GST genotypes was 1.42 (1.12–1.81) and 1.71 (1.25–2.34), respectively, relative to the absence of null/low-activity GST genotype. NAT2 slow acetylation was associated with doubled risk of bladder cancer among individuals with known high exposures to carcinogenic arylamines (OR = 2.03, 95% CI = 1.12–3.69, P = 0.02). The effect of NAT2 slow acetylation was even stronger in the presence of two or more null/low-activity GST genotypes. There were no associations between bladder cancer risk and NAT1 genotype or CYP1A2 phenotype. PMID:18544563

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

PubMed

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.

Bladder cancer mortality trends and patterns in Córdoba, Argentina (1986-2006).

PubMed

Pou, Sonia Alejandra; Osella, Alberto Ruben; Diaz, Maria Del Pilar

2011-03-01

Bladder cancer is common worldwide and the fourth most commonly diagnosed malignancy in men in Argentina. To describe bladder cancer mortality trends in Córdoba (1986-2006), considering the effect of age, period, and cohort, and to estimate the effect of arsenic exposure on bladder cancer, and its interaction with sex, while controlling by smoking habits and space and time variation of the rates. A joinpoint regression was performed to compute the estimated annual percentage changes (EAPC) of the age-standardized mortality rates (ASMR) in an adult population from Córdoba, Argentina. A Poisson model was fitted to estimate the effect of age, period, and cohort. The influence of gender, tobacco smoking (using lung cancer ASMR as surrogate), and arsenic in drinking water was examined using a hierarchical model. A favorable trend (1986-2006) in bladder cancer ASMR in both sexes was found: EAPC of -2.54 in men and -1.69 in women. There was a decreasing trend in relative risk (RR) for cohorts born in 1931 or after. The multilevel model showed an increasing risk for each increase in lung cancer ASMR unit (RR = 1.001) and a biological interaction between sex and arsenic exposure. RR was higher among men exposed to increasing As-exposure categories (RR male low exposure 3.14, RR male intermediate exposure 4.03, RR male high exposure 4.71 versus female low exposure). A non-random space-time distribution of the rates was observed. There has been a decreasing trend in ASMR for bladder cancer in Córdoba. This study confirms that bladder cancer is associated with age, gender, smoking habit, and exposure to arsenic. Moreover, an effect measure modification between exposure to arsenic and sex was found.

Bladder Preservation for Localized Muscle-Invasive Bladder Cancer: The Survival Impact of Local Utilization Rates of Definitive Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kozak, Kevin R.; Hamidi, Maryam; Manning, Matthew

2012-06-01

Purpose: This study examines the management and outcomes of muscle-invasive bladder cancer in the United States. Methods and Materials: Patients with muscle-invasive bladder cancer diagnosed between 1988 and 2006 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Patients were classified according to three mutually exclusive treatment categories based on the primary initial treatment: no local management, radiotherapy, or surgery. Overall survival was assessed with Kaplan-Meier analysis and Cox models based on multiple factors including treatment utilization patterns. Results: The study population consisted of 26,851 patients. Age, sex, race, tumor grade, histology, and geographic location were associated withmore » differences in treatment (all p < 0.01). Patients receiving definitive radiotherapy tended to be older and have less differentiated tumors than patients undergoing surgery (RT, median age 78 years old and 90.6% grade 3/4 tumors; surgery, median age 71 years old and 77.1% grade 3/4 tumors). No large shifts in treatment were seen over time, with most patients managed with surgical resection (86.3% for overall study population). Significant survival differences were observed according to initial treatment: median survival, 14 months with no definitive local treatment; 17 months with radiotherapy; and 43 months for surgery. On multivariate analysis, differences in local utilization rates of definitive radiotherapy did not demonstrate a significant effect on overall survival (hazard ratio, 1.002; 95% confidence interval, 0.999-1.005). Conclusions: Multiple factors influence the initial treatment strategy for muscle-invasive bladder cancer, but definitive radiotherapy continues to be used infrequently. Although patients who undergo surgery fare better, a multivariable model that accounted for patient and tumor characteristics found no survival detriment to the utilization of definitive radiotherapy. These results support continued research into bladder preservation strategies and suggest that definitive radiotherapy represents a viable initial treatment strategy for those who wish to attempt to preserve their native bladder.« less

Dosimetric impact in the dose-volume histograms of rectal and vesical wall contouring in prostate cancer IMRT treatments.

PubMed

Gómez, Laura; Andrés, Carlos; Ruiz, Antonio

2017-01-01

The main purpose of this study was to evaluate the differences in dose-volume histograms of IMRT treatments for prostate cancer based on the delineation of the main organs at risk (rectum and bladder) as solid organs or by contouring their wall. Rectum and bladder have typically been delineated as solid organs, including the waste material, which, in practice, can lead to an erroneous assessment of the risk of adverse effects. A retrospective study was made on 25 patients treated with IMRT radiotherapy for prostate adenocarcinoma. 76.32 Gy in 36 fractions was prescribed to the prostate and seminal vesicles. In addition to the delineation of the rectum and bladder as solid organs (including their content), the rectal and bladder wall were also delineated and the resulting dose-volume histograms were analyzed for the two groups of structures. Data analysis shows statistically significant differences in the main parameters used to assess the risk of toxicity of a prostate radiotherapy treatment. Higher doses were received on the rectal and bladder walls compared to doses received on the corresponding solid organs. The observed differences in terms of received doses to the rectum and bladder based on the method of contouring could gain greater importance in inverse planning treatments, where the treatment planning system optimizes the dose in these volumes. So, one should take into account the method of delineating of these structures to make a clinical decision regarding dose limitation and risk assessment of chronic toxicity.

Modelling second malignancy risks from low dose rate and high dose rate brachytherapy as monotherapy for localised prostate cancer.

PubMed

Murray, Louise; Mason, Joshua; Henry, Ann M; Hoskin, Peter; Siebert, Frank-Andre; Venselaar, Jack; Bownes, Peter

2016-08-01

To estimate the risks of radiation-induced rectal and bladder cancers following low dose rate (LDR) and high dose rate (HDR) brachytherapy as monotherapy for localised prostate cancer and compare to external beam radiotherapy techniques. LDR and HDR brachytherapy monotherapy plans were generated for three prostate CT datasets. Second cancer risks were assessed using Schneider's concept of organ equivalent dose. LDR risks were assessed according to a mechanistic model and a bell-shaped model. HDR risks were assessed according to a bell-shaped model. Relative risks and excess absolute risks were estimated and compared to external beam techniques. Excess absolute risks of second rectal or bladder cancer were low for both LDR (irrespective of the model used for calculation) and HDR techniques. Average excess absolute risks of rectal cancer for LDR brachytherapy according to the mechanistic model were 0.71 per 10,000 person-years (PY) and 0.84 per 10,000 PY respectively, and according to the bell-shaped model, were 0.47 and 0.78 per 10,000 PY respectively. For HDR, the average excess absolute risks for second rectal and bladder cancers were 0.74 and 1.62 per 10,000 PY respectively. The absolute differences between techniques were very low and clinically irrelevant. Compared to external beam prostate radiotherapy techniques, LDR and HDR brachytherapy resulted in the lowest risks of second rectal and bladder cancer. This study shows both LDR and HDR brachytherapy monotherapy result in low estimated risks of radiation-induced rectal and bladder cancer. LDR resulted in lower bladder cancer risks than HDR, and lower or similar risks of rectal cancer. In absolute terms these differences between techniques were very small. Compared to external beam techniques, second rectal and bladder cancer risks were lowest for brachytherapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hypoxic exosomes facilitate bladder tumor growth and development through transferring long non-coding RNA-UCA1.

PubMed

Xue, Mei; Chen, Wei; Xiang, An; Wang, Ruiqi; Chen, He; Pan, Jingjing; Pang, Huan; An, Hongli; Wang, Xiang; Hou, Huilian; Li, Xu

2017-08-25

To overcome the hostile hypoxic microenvironment of solid tumors, tumor cells secrete a large number of non-coding RNA-containing exosomes that facilitate tumor development and metastasis. However, the precise mechanisms of tumor cell-derived exosomes during hypoxia are unknown. Here, we aim to clarify whether hypoxia affects tumor growth and progression by transferring long non-coding RNA-urothelial cancer-associated 1 (lncRNA-UCA1) enriched exosomes secreted from bladder cancer cells. We used bladder cancer 5637 cells with high expression of lncRNA-UCA1 as exosome-generating cells and bladder cancer UMUC2 cells with low expression of lncRNA-UCA1 as recipient cells. Exosomes derived from 5637 cells cultured under normoxic or hypoxic conditions were isolated and identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting analysis. These exosomes were co-cultured with UMUC2 cells to evaluate cell proliferation, migration and invasion. We further investigated the roles of exosomal lncRNA-UCA1 derived from hypoxic 5637 cells by xenograft models. The availability of lncRNA-UCA1 in serum-derived exosomes as a biomarker for bladder cancer was also assessed. We found that hypoxic exosomes derived from 5637 cells promoted cell proliferation, migration and invasion, and hypoxic exosomal RNAs could be internalized by three bladder cancer cell lines. Importantly, lncRNA-UCA1 was secreted in hypoxic 5637 cell-derived exosomes. Compared with normoxic exosomes, hypoxic exosomes derived from 5637 cells showed the higher expression levels of lncRNA-UCA1. Moreover, Hypoxic exosomal lncRNA-UCA1 could promote tumor growth and progression though epithelial-mesenchymal transition, in vitro and in vivo. In addition, the expression levels of lncRNA-UCA1 in the human serum-derived exosomes of bladder cancer patients were higher than that in the healthy controls. Together, our results demonstrate that hypoxic bladder cancer cells remodel tumor microenvironment to facilitate tumor growth and development though secreting the oncogenic lncRNA-UCA1-enriched exosomes and exosomal lncRNA-UCA1 in human serum has the possibility as a diagnostic biomarker for bladder cancer.

Proteomics Analysis of Bladder Cancer Exosomes*

PubMed Central

Welton, Joanne L.; Khanna, Sanjay; Giles, Peter J.; Brennan, Paul; Brewis, Ian A.; Staffurth, John; Mason, Malcolm D.; Clayton, Aled

2010-01-01

Exosomes are nanometer-sized vesicles, secreted by various cell types, present in biological fluids that are particularly rich in membrane proteins. Ex vivo analysis of exosomes may provide biomarker discovery platforms and form non-invasive tools for disease diagnosis and monitoring. These vesicles have never before been studied in the context of bladder cancer, a major malignancy of the urological tract. We present the first proteomics analysis of bladder cancer cell exosomes. Using ultracentrifugation on a sucrose cushion, exosomes were highly purified from cultured HT1376 bladder cancer cells and verified as low in contaminants by Western blotting and flow cytometry of exosome-coated beads. Solubilization in a buffer containing SDS and DTT was essential for achieving proteomics analysis using an LC-MALDI-TOF/TOF MS approach. We report 353 high quality identifications with 72 proteins not previously identified by other human exosome proteomics studies. Overrepresentation analysis to compare this data set with previous exosome proteomics studies (using the ExoCarta database) revealed that the proteome was consistent with that of various exosomes with particular overlap with exosomes of carcinoma origin. Interrogating the Gene Ontology database highlighted a strong association of this proteome with carcinoma of bladder and other sites. The data also highlighted how homology among human leukocyte antigen haplotypes may confound MASCOT designation of major histocompatability complex Class I nomenclature, requiring data from PCR-based human leukocyte antigen haplotyping to clarify anomalous identifications. Validation of 18 MS protein identifications (including basigin, galectin-3, trophoblast glycoprotein (5T4), and others) was performed by a combination of Western blotting, flotation on linear sucrose gradients, and flow cytometry, confirming their exosomal expression. Some were confirmed positive on urinary exosomes from a bladder cancer patient. In summary, the exosome proteomics data set presented is of unrivaled quality. The data will aid in the development of urine exosome-based clinical tools for monitoring disease and will inform follow-up studies into varied aspects of exosome manufacture and function. PMID:20224111

What are the currently available and in development molecular markers for bladder cancer? Will they prove to be useful in the future?

PubMed

Abdulmajed, Mohamed Ismat; Sancak, Eyüp Burak; Reşorlu, Berkan; Al-Chalaby, Gydhia Zuhair

2014-12-01

Urothelial carcinoma is the 9(th) most common cancer worldwide. Most urothelial tumors are non-muscle invasive on presentation. However, two-thirds of non-invasive bladder cancers will eventually recur with a 25% risk of progression to muscle-invasive bladder cancer. Tumor stage, histological grade and pathological invasion of blood vessels and lymphatic tissue are the main indicators for urothelial cancer prognosis. The gold standard for diagnosing bladder cancer is conventional white-light cystoscopy and biopsy. Urine cytology is a highly specific, sensitive test for high-grade tumors or carcinoma in situ (CIS). Urinary NMP22 has an overall sensitivity and specificity for detecting bladder cancer of 49% and 87%, respectively. However, there are false-positive results in the presence of urinary tract infection or hematuria. The detection of specific gene mutations related to urothelial cancers has been studied and employed to reproduce markers helpful for diagnosis. According to current studies, molecular markers can be used to predict tumor recurrence. From a prognostic point of view, new molecular markers have yet to be established as reliable indicators of tumor aggressiveness. We aimed to review the molecular markers with possible prognostic significance that have been discussed in the literature. This review examined the literature for various molecular markers under development for bladder cancer in an attempt to optimize patient care and reduce the costs of treating these patients.

A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: The future is now.

PubMed

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. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quality-of-life survey for patients diagnosed with nonmuscle-invasive bladder cancer.

PubMed

Abáigar-Pedraza, I; Megías-Garrigós, J; Sánchez-Payá, J

2016-05-01

To determine the reliability and validity of a quality-of-life survey for patients with nonmuscle-invasive bladder cancer. A total of 180 patients were included in the study. We developed a survey with 21 questions grouped into 5 areas. The patients filled in this survey and the Functional Assessment of Cancer Therapy - Bladder Cancer (FACT-BL) survey. To assess reliability, we calculated Cronbach's alpha coefficient and the kappa index. To determine criterion validity, we studied the association between the scores obtained from our survey and those from the FACT-BL survey using the Pearson correlation coefficient. To determine the construct validity (factorial and discriminatory), we performed a factor analysis, comparing it with Student's t-test for the scores obtained according to the tumour characteristics of reduced quality of life (e.g., malignancies located at the trigone of the bladder). Cronbach's alpha reliability coefficient was .83, and the kappa index varied between .7 and 1. For the association study between the new survey and the FACT-BL survey, we measured an r=.82 for the overall score and between r=.68 (disease) and r=.97 (sex life) in the various measures. In the factor analysis, we measured a Kaiser-Meyer-Olkin index of .77 and performed the Barlett test (P<.001). The comparison between the scores, in the presence or absence of certain tumour characteristics, has shown a reduced quality of life when those characteristics are present, which was statistically significant (P<.05) in the majority of cases. Our survey to measure the quality of life of patients with nonmuscle-invasive bladder cancer is reliable and valid. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

A systematic review of exercise and psychosocial rehabilitation interventions to improve health-related outcomes in patients with bladder cancer undergoing radical cystectomy.

PubMed

Rammant, Elke; Decaestecker, Karel; Bultijnck, Renée; Sundahl, Nora; Ost, Piet; Pauwels, Nele S; Deforche, Benedicte; Pieters, Ronny; Fonteyne, Valérie

2018-05-01

Summarizing the evidence on the effects of pre- and postoperative exercise and psychosocial rehabilitation interventions on patient-reported outcomes (PROs) and physical fitness in bladder cancer patients undergoing radical cystectomy. The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Web of Science and the Physiotherapy Evidence Database were searched independently by two authors from inception until 10 November 2017. Cited references of the studies and citing references retrieved via Web of Science were also checked. Randomized controlled trials (RCTs) and non-randomized studies assessing effects of exercise and psychosocial interventions in bladder cancer patients undergoing radical cystectomy were eligible. Primary outcome measures were PROs and physical fitness. Risk of bias was assessed using the Cochrane Collaboration tool and the Newcastle-Ottawa Scale. Five RCTs (three exercise and two psychosocial studies) and one non-randomized psychosocial study comprising 317 bladder cancer patients were included. Timing of the intervention was preoperative ( n = 2), postoperative ( n = 2) or both pre- and postoperative ( n = 2). Positive effects of exercise were found for physical fitness ( n = 3), some health-related quality-of-life (HRQoL) domains ( n = 2), personal activities in daily living ( n = 1) and muscle strength ( n = 1). Psychosocial interventions showed positive effects on anxiety ( n = 1), fatigue ( n = 1), depression ( n = 1), HRQoL ( n = 1) and posttraumatic growth ( n = 1). Quality assessment showed most shortcomings with sample sizes and strong heterogeneity was observed between studies. The evidence relating to the effects of exercise in bladder cancer is very limited and is even less for psychosocial interventions.

Fibroblast growth factor receptor 1 and cytokeratin 20 expressions and their relation to prognostic variables in bladder cancer.

PubMed

Abdul-Maksoud, Rehab S; Shalaby, Sally M; Elsayed, Walid S H; Elkady, Saad

2016-10-15

Tumor grade and stage are currently the most important prognostic variables in bladder cancer but establishing additional criteria is still needed for effective treatment. The aim of the study was to assess the expression of fibroblast growth factor receptor 1 (FGFR1) and cytokeratin 20 (CK20) in cancer bladder (CB) and to evaluate their association with the clinicopathological features of the disease. The study included 80 patients diagnosed as bladder cancer of different stages and grades and 80 patients with nonmalignant urothelial diseases of matched age and sex to the malignant group. The expressions of FGFR1 and CK20 in tissue samples were determined by RT-PCR and immunohistochemistry. The expression levels of FGFR1 and CK20 were increased in the malignant group when compared to the control group (P<0.001 for each). Analysis of their expression showed that levels of FGFR1 and CK20 were significantly higher in invasive tumor stages (pT2-pT4) than in non-invasive stages (pTis, pTa, pT1) (P<0.001). Interestingly, the sensitivity and specificity of combined detection with CK20 and FGFR1 for the differentiation between invasive and non-invasive stages of bladder cancer reached 97.5% and 92.5%, respectively. Our results determined overexpression of both FGFR1 and CK20 in CB specimens. The alterations in the expression of FGFR1 and CK20 were associated with disease stage and grade. Lastly, combined detection of FGFR1 and CK20 had a high predictive prognostic value in differentiating invasive from non-invasive carcinoma. Copyright © 2016 Elsevier B.V. All rights reserved.

Pioglitazone use and risk of bladder cancer in patients with type 2 diabetes: retrospective cohort study using datasets from four European countries.

PubMed

Korhonen, Pasi; Heintjes, Edith M; Williams, Rachael; Hoti, Fabian; Christopher, Solomon; Majak, Maila; Kool-Houweling, Leanne; Strongman, Helen; Linder, Marie; Dolin, Paul; Bahmanyar, Shahram

2016-08-16

 To evaluate the association between pioglitazone use and bladder cancer risk in patients with type 2 diabetes.  Retrospective cohort study using propensity score matched cohorts.  Healthcare databases from Finland, the Netherlands, Sweden, and the United Kingdom. Data comprised country specific datasets of linked records on prescriptions, hospitals, general practitioners, cancer, and deaths.  Patients with type 2 diabetes who initiated pioglitazone (n=56 337) matched with patients with type 2 diabetes in the same country exposed to diabetes drug treatments other than pioglitazone (n=317 109). Two matched cohorts were created, using a 1:1 fixed ratio (nearest match cohort) and a 1:10 variable ratio (multiple match cohort). Patients were matched on treatment history and propensity scores accounting for several variables associated with pioglitazone initiation.  Hazard ratios and 95% confidence intervals were estimated by Cox's proportional hazards model with adjustments for relevant confounders. To assess the robustness of the findings, several sensitivity and stratified analyses were performed.  In the cohort exposed to pioglitazone treatment, 130 bladder cancers occurred over a mean follow-up time of 2.9 years. In the nearest match and multiple match cohorts not exposed to pioglitazone treatment, 153 and 970 bladder cancers were recorded, with a mean follow‑up time of 2.8 and 2.9 years, respectively. With regards to bladder cancer risk, the adjusted hazard ratio for patients ever exposed versus never exposed to pioglitazone was 0.99 (95% confidence interval 0.75 to 1.30) and 1.00 (0.83 to 1.21) in the nearest and multiple match cohorts, respectively. Increasing duration of pioglitazone use and increasing cumulative dose were not associated with risk of bladder cancer (>48 months of pioglitazone use, adjusted hazard ratio 0.86 (0.44 to 1.66); >40 000 mg cumulative dose, 0.65 (0.33 to 1.26) in the nearest match cohort).  This study shows no evidence of an association between ever use of pioglitzone and risk of bladder cancer compared with never use, which is consistent with results from other recent studies that also included a long follow-up period.  Registered to the European Union electronic register of post-authorisation studies (EU PAS register no EUPAS3626). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Androgen Receptor Signaling in Bladder Cancer

PubMed Central

Li, Peng; Chen, Jinbo; Miyamoto, Hiroshi

2017-01-01

Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific differences in bladder cancer. This review summarizes and discusses the available data, suggesting the involvement of androgens and/or the androgen receptor pathways in urothelial carcinogenesis as well as tumor growth. While the precise mechanisms of the functions of the androgen receptor in urothelial cells remain far from being fully understood, current evidence may offer chemopreventive or therapeutic options, using androgen deprivation therapy, in patients with bladder cancer. PMID:28241422

Transurethral resection and degeneration of bladder tumour

PubMed Central

Li, Aihua; Fang, Wei; Zhang, Feng; Li, Weiwu; Lu, Honghai; Liu, Sikuan; Wang, Hui; Zhang, Binghui

2013-01-01

Introduction: We evaluate the efficacy and safety of transurethral resection and degeneration of bladder tumour (TURD-Bt). Methods: In total, 56 patients with bladder tumour were treated by TURD-Bt. The results in these patients were compared with 32 patients treated by current transurethral resection of bladder tumour (TUR-Bt). Patients with or without disease progressive factors were respectively compared between the 2 groups. The factors included recurrent tumour, multiple tumours, tumour ≥3 cm in diameter, clinical stage T2, histological grade 3, adenocarcinoma, and ureteral obstruction or hydronephrosis. Results: Follow-up time was 48.55 ± 23.74 months in TURD-Bt group and 56.28 ± 17.61 months in the TUR-Bt group (p > 0.05). In patients without progressive factors, no tumour recurrence was found and overall survival was 14 (100%) in the TURD-Bt group; 3 (37.50%) patients had recurrence and overall survival was 5 (62.5%) in the TUR-Bt group. In patients with progressive factors, 8 (19.05%) patients had tumour recurrence, overall survival was 32 (76.19%) and cancer death was 3 (7.14%) in TURD-Bt group; 18 (75.00%) patients had tumour recurrence (p < 0.05), overall survival was 12 (50.00%) (p < 0.01) and cancer death was 8 (33.33%) (p < 0.05) in TUR-Bt group. No significant complication was found in TURD-Bt group. Conclusion: This study suggests that complete resection and degeneration of bladder tumour can be expected by TURD-Bt. The surgical procedure is safe and efficacious, and could be predictable and controllable before and during surgery. We would conclude that for bladder cancers without lymph node metastasis and distal metastasis, TURD-Bt could be performed to replace radical TUR-Bt and preserve the bladder. PMID:24475002

Non-invasive prediction of recurrence in bladder cancer by detecting somatic TERT promoter mutations in urine.

PubMed

Descotes, Françoise; Kara, Norelyakin; Decaussin-Petrucci, Myriam; Piaton, Eric; Geiguer, Florence; Rodriguez-Lafrasse, Claire; Terrier, Jean E; Lopez, Jonathan; Ruffion, Alain

2017-08-08

Urothelial bladder cancer (UBC) is characterised by a high risk of recurrence. Patient monitoring is currently based on iterative cystoscopy and on urine cytology with low sensitivity in non-muscle-invasive bladder cancer (NMIBC). Telomerase reverse transcriptase (TERT) is frequently reactivated in UBC by promoter mutations. We studied whether detection of TERT mutation in urine could be a predictor of UBC recurrence and compared this to cytology/cystoscopy for patient follow-up. A total of 348 patients treated by transurethral bladder resection for UBC were included together with 167 control patients. Overall sensitivity was 80.5% and specificity 89.8%, and was not greatly impacted by inflammation or infection. TERT remaining positive after initial surgery was associated with residual carcinoma in situ. TERT in urine was a reliable and dynamic predictor of recurrence in NMIBC (P<0.0001). In univariate analysis, TERT positive-status after initial surgery increased risk of recurrence by 5.34-fold (P=0.0004). TERT positive-status was still associated with recurrence in the subset of patients with negative cystoscopy (P=0.034). TERT mutations in urine might be helpful for early detection of recurrence in UBC, especially in NMIBC.

Current preclinical models for the advancement of translational bladder cancer research.

PubMed

DeGraff, David J; Robinson, Victoria L; Shah, Jay B; Brandt, William D; Sonpavde, Guru; Kang, Yibin; Liebert, Monica; Wu, Xue-Ru; Taylor, John A

2013-02-01

Bladder cancer is a common disease representing the fifth most diagnosed solid tumor in the United States. Despite this, advances in our understanding of the molecular etiology and treatment of bladder cancer have been relatively lacking. This is especially apparent when recent advances in other cancers, such as breast and prostate, are taken into consideration. The field of bladder cancer research is ready and poised for a series of paradigm-shifting discoveries that will greatly impact the way this disease is clinically managed. Future preclinical discoveries with translational potential will require investigators to take full advantage of recent advances in molecular and animal modeling methodologies. We present an overview of current preclinical models and their potential roles in advancing our understanding of this deadly disease and for advancing care. ©2012 AACR.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin Jie; Xie Liping; Zheng Xiangyi

Bladder cancer is the fourth most common cancer in men and ninth most common in women. It has a protracted course of progression and is thus an ideal candidate for chemoprevention strategies and trials. This study was conducted to evaluate the chemopreventive/antiproliferative potential of (-)-epigallocatechin gallate (EGCG, the major phytochemical in green tea) against bladder cancer and its mechanism of action. Using the T24 human bladder cancer cell line, we found that EGCG treatment caused dose- and time-dependent inhibition of cellular proliferation and cell viability, and induced apoptosis. Mechanistically, EGCG inhibits phosphatidylinositol 3'-kinase/Akt activation that, in turn, results in modulationmore » of Bcl-2 family proteins, leading to enhanced apoptosis of T24 cells. These findings suggest that EGCG may be an important chemoprevention agent for the management of bladder cancer.« less

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

PubMed

Memon, Ashfaque A; Chang, Jong W; Oh, Bong R; Yoo, Yung J

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 and identified by peptide mass fingerprinting using mass spectrometry and database search. We found most extensive and reproducible down-regulation of NADP dependent isocitrate dehydrogenase cytoplasmic (IDPc) and peroxiredoxin-II (Prx-II), in poorly differentiated T24 compared to well-differentiated RT4 bladder 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 involve in tumor progression and metastasis. However, additional investigations are needed on large number of human samples to further verify these findings.

A Review of ERCC1 Gene in Bladder Cancer: Implications for Carcinogenesis and Resistance to Chemoradiotherapy.

PubMed

Kawashima, Atsunari; Takayama, Hitoshi; Tsujimura, Akira

2012-01-01

The excision repair cross-complementing group 1 (ERCC1) gene performs a critical incision step in DNA repair and is reported to be correlated with carcinogenesis and resistance to drug or ionizing radiation therapy. We reviewed the correlation between ERCC1 and bladder cancer. In carcinogenesis, several reports discussed the relation between ERCC1 single nucleotide polymorphisms and carcinogenesis in bladder cancer only in case-control studies. Regarding the relation between ERCC1 and resistance to chemoradiotherapy, in vitro and clinical studies indicate that ERCC1 might be related to resistance to radiation therapy rather than cisplatin therapy. It is controversial whether ERCC1 predicts prognosis of bladder cancer treated with cisplatin-based chemotherapy. Tyrosine kinase receptors or endothelial-mesenchymal transition are reported to regulate the expression of ERCC1, and further study is needed to clarify the mechanism of ERCC1 expression and resistance to chemoradiotherapy in vitro and to discover novel therapies for advanced and metastatic bladder cancer.

Association between the high risk occupations and bladder cancer in Iran: a case-control study.

PubMed

Khoubi, Jamshid; Pourabdian, Siamak; Mohebbi, Iraj; Tajvidi, Mina; Zaroorian, Omid; Giahi, Omid

2013-04-01

The objective of this work was to identify the high-risk occupations in Iran and to re-inspect occupations that were related to bladder cancer. In the study, 300 patients suffering from bladder cancer and 500 control individuals were interviewed. Demographic information, occupational history, and history of exposure to chemical compounds such as aromatic amines for each participant were collected. ORs and 95% CIs were calculated using unconditional logistic regression for each occupation. There was a significantly increased risk of bladder cancer among truck and bus drivers (OR = 11.3), skilled agricultural, forestry and fishery workers (OR = 6.0), metal industry workers (OR = 6.0), domestic housekeepers (OR = 5.9), and construction workers (OR = 3.8). The study showed a strong correlation between truck and bus drivers, skilled agricultural, forestry and fishery workers, metal industry workers, domestic housekeepers, as well as construction workers and the increased risk of bladder cancer in these occupations.

Roles of ERβ and GPR30 in Proliferative Response of Human Bladder Cancer Cell to Estrogen.

PubMed

Huang, Weiren; Chen, Yuanbin; Liu, Yuchen; Zhang, Qiaoxia; Yu, Zhou; Mou, Lisha; Wu, Hanwei; Zhao, Li; Long, Ting; Qin, Danian; Gui, Yaoting

2015-01-01

Bladder cancer belongs to one of the most common cancers and is a leading cause of deaths in our society. Urothelial carcinoma of the bladder (UCB) is the main type of this cancer, and the estrogen receptors in UCB remain to be studied. Our experiment aimed to investigate the possible biological effect of 17β-estradiol on human bladder-derived T24 carcinoma cells and to indicate its related mechanisms. T24 cells were treated with various doses of 17β-estradiol, and cell proliferation was detected using MTT assays. 17β-estradiol promoted T24 cell proliferation independent of ERβ/GPR30-regulated EGFR-MAPK pathway, while it inhibited cell growth via GPR30. Furthermore, the expression levels of downstream genes (c-FOS, BCL-2, and CYCLIN D1) were increased by 17β-estradiol and this effect was independently associated with activity of the EGFR-MAPK pathway. The two estrogen receptors might be potential therapeutic targets for the treatment of bladder cancer.

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

PubMed

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.

Understanding the Role of Non-Coding RNAs in Bladder Cancer: From Dark Matter to Valuable Therapeutic Targets

PubMed Central

Pop-Bica, Cecilia; Gulei, Diana; Cojocneanu-Petric, Roxana; Braicu, Cornelia; Petrut, Bogdan; Berindan-Neagoe, Ioana

2017-01-01

The mortality and morbidity that characterize bladder cancer compel this malignancy into the category of hot topics in terms of biomolecular research. Therefore, a better knowledge of the specific molecular mechanisms that underlie the development and progression of bladder cancer is demanded. Tumor heterogeneity among patients with similar diagnosis, as well as intratumor heterogeneity, generates difficulties in terms of targeted therapy. Furthermore, late diagnosis represents an ongoing issue, significantly reducing the response to therapy and, inevitably, the overall survival. The role of non-coding RNAs in bladder cancer emerged in the last decade, revealing that microRNAs (miRNAs) may act as tumor suppressor genes, respectively oncogenes, but also as biomarkers for early diagnosis. Regarding other types of non-coding RNAs, especially long non-coding RNAs (lncRNAs) which are extensively reviewed in this article, their exact roles in tumorigenesis are—for the time being—not as evident as in the case of miRNAs, but, still, clearly suggested. Therefore, this review covers the non-coding RNA expression profile of bladder cancer patients and their validated target genes in bladder cancer cell lines, with repercussions on processes such as proliferation, invasiveness, apoptosis, cell cycle arrest, and other molecular pathways which are specific for the malignant transformation of cells. PMID:28703782

Understanding the Role of Non-Coding RNAs in Bladder Cancer: From Dark Matter to Valuable Therapeutic Targets.

PubMed

Pop-Bica, Cecilia; Gulei, Diana; Cojocneanu-Petric, Roxana; Braicu, Cornelia; Petrut, Bogdan; Berindan-Neagoe, Ioana

2017-07-13

The mortality and morbidity that characterize bladder cancer compel this malignancy into the category of hot topics in terms of biomolecular research. Therefore, a better knowledge of the specific molecular mechanisms that underlie the development and progression of bladder cancer is demanded. Tumor heterogeneity among patients with similar diagnosis, as well as intratumor heterogeneity, generates difficulties in terms of targeted therapy. Furthermore, late diagnosis represents an ongoing issue, significantly reducing the response to therapy and, inevitably, the overall survival. The role of non-coding RNAs in bladder cancer emerged in the last decade, revealing that microRNAs (miRNAs) may act as tumor suppressor genes, respectively oncogenes, but also as biomarkers for early diagnosis. Regarding other types of non-coding RNAs, especially long non-coding RNAs (lncRNAs) which are extensively reviewed in this article, their exact roles in tumorigenesis are-for the time being-not as evident as in the case of miRNAs, but, still, clearly suggested. Therefore, this review covers the non-coding RNA expression profile of bladder cancer patients and their validated target genes in bladder cancer cell lines, with repercussions on processes such as proliferation, invasiveness, apoptosis, cell cycle arrest, and other molecular pathways which are specific for the malignant transformation of cells.

Bacillus Calmette-Guérin enhances production and secretion of type IV collagenases in peripheral blood mononuclear cells.

PubMed

Kageyama, Y; Kawakami, S; Fujii, Y; Kihara, K; Oshima, H

1997-03-01

Intravesical administration of bacillus Calmette-Guérin (BCG) is an effective and widely accepted treatment for superficial bladder cancer. Rapid progression of the disease after BCG therapy, however, has been reported in some cases refractory to the treatment. We examined whether BCG treatment and coexistence of peripheral blood mononuclear cells (PBMCs) alter the invasive potential of bladder cancer cells. Production and secretion of two type IV collagenases, matrix metalloproteinase (MMP) 2 and MMP 9, by PBMCs from five healthy donors or bladder cancer cells (T24, JTC 30, and JTC 32) were evaluated by gelatin zymography, western blot analysis, and northern blot analysis. Invasion of bladder cancer cells was also examined using reconstituted basement membrane (Matrigel). BCG (5, 50, and 500 micrograms/ml) had no effect on secretion of MMP 2 and MMP 9 by bladder cancer cells, but increased the production and secretion of MMP 9 by PBMCs in a dose-dependent manner. The coexistence of PBMCs increased invasion of T24 cells and BCG further enhanced the invasion. Thus, BCG promotes invasion of bladder cancer cells under certain conditions. An increase in the secretion of MMP 9 by PBMCs may account in part for the effect.

Sex differences in the MB49 syngeneic, murine model of bladder cancer

PubMed Central

White-Gilbertson, Shai; Davis, Megan; Voelkel-Johnson, Christina; Kasman, Laura M.

2016-01-01

OBJECTIVE The MB49 syngeneic, murine model of bladder cancer has been widely used for more than 35 years. In humans, bladder cancer is one third as prevalent in women as in men, with a trend toward lower prevalence in parous compared to nulliparous women. Our objective was to determine if the MB49 bladder cancer model reproduces the sex differences observed in humans, and to determine its sensitivity to testosterone and the pregnancy hormone, human chorionic gonadotropin (hCG). METHODS Male and female C57BL/6 mice were implanted with MB49 murine bladder cancer cells, and observed for tumor growth. MB49 dose responses to hCG and dihydrotestosterone were determined in vitro. RESULTS MB49 tumor growth was significantly greater in male mice than female mice. Pregnancy did not affect MB49 tumor growth in female mice. MB49 cells did not proliferate in response to hCG in vitro and the functional receptor for gonadotropins was absent. Dihydrotestosterone strongly stimulated growth of MB49 cells in vitro. CONCLUSIONS The MB49 murine model of bladder cancer reproduced some aspects of the sex differences observed in humans. Our results suggest that testosterone may stimulate MB49 cell proliferation, which may explain the more rapid MB49 tumor growth observed in male mice. PMID:26998503

Sex differences in the MB49 syngeneic, murine model of bladder cancer.

PubMed

White-Gilbertson, Shai; Davis, Megan; Voelkel-Johnson, Christina; Kasman, Laura M

The MB49 syngeneic, murine model of bladder cancer has been widely used for more than 35 years. In humans, bladder cancer is one third as prevalent in women as in men, with a trend toward lower prevalence in parous compared to nulliparous women. Our objective was to determine if the MB49 bladder cancer model reproduces the sex differences observed in humans, and to determine its sensitivity to testosterone and the pregnancy hormone, human chorionic gonadotropin (hCG). Male and female C57BL/6 mice were implanted with MB49 murine bladder cancer cells, and observed for tumor growth. MB49 dose responses to hCG and dihydrotestosterone were determined in vitro . MB49 tumor growth was significantly greater in male mice than female mice. Pregnancy did not affect MB49 tumor growth in female mice. MB49 cells did not proliferate in response to hCG in vitro and the functional receptor for gonadotropins was absent. Dihydrotestosterone strongly stimulated growth of MB49 cells in vitro . The MB49 murine model of bladder cancer reproduced some aspects of the sex differences observed in humans. Our results suggest that testosterone may stimulate MB49 cell proliferation, which may explain the more rapid MB49 tumor growth observed in male mice.

Comparison of the safety and efficacy of conventional monopolar and 2-micron laser transurethral resection in the management of multiple nonmuscle-invasive bladder cancer.

PubMed

Liu, H; Wu, J; Xue, S; Zhang, Q; Ruan, Y; Sun, X; Xia, S

2013-08-01

To compare the safety and efficacy of conventional monopolar transurethral resection of bladder tumour (TURBT) and 2-micron continuous-wave laser resection (2-µm laser) techniques in the management of multiple nonmuscle-invasive bladder cancer (NMIBC), and to investigate long-term effects on tumour recurrence. Patients with multiple NMIBC were randomized to receive TURBT or 2-µm laser in a nonblinded manner. All patients received intravesical chemotherapy with epirubicin (40 mg/40 ml) for 8 weeks, beginning 1 week after surgery, followed with monthly maintenance therapy for 12 months. Three-year follow-up data of preoperative, operative and postoperative management were recorded. In total, 120 patients were included: 56 in the TURBT group and 64 in the 2-µm laser group. Intra- and postoperative complications (including bladder perforation, bleeding and irritation) were less frequently observed in the 2-µm laser group compared with the TURBT group. There were no significant differences in first time to recurrence, overall recurrence or occurrence of urethral strictures. The 2-µm laser resection method was more effective than TURBT in reducing rates of intra- and postoperative complications, but offered no additional benefit regarding tumour recurrence.

GENE EXPRESSION DOSE-RESPONSE IN THE MOUSE BLADDER FOLLOWING EXPOSURE TO ARSENATE IN DRINKING WATER

EPA Science Inventory

The association between drinking water exposures to inorganic arsenic and life-threatening tumors in the human is strongest for bladder cancer. Moreover, a working model for the pathogenesis of human bladder cancer has been developed. To investigate the mode of action for inorgan...

The cytostatic effect of 9-cis-retinoic acid, tretinoin, and isotretinoin on three different human bladder cancer cell lines in vitro.

PubMed

Laaksovirta, S; Rajala, P; Nurmi, M; Tammela, T L; Laato, M

1999-01-01

Retinoids have been shown to have activity in both preclinical and clinical bladder cancer studies but their exact role in its treatment and prevention remains obscure. In this study cytostatic activity of a novel 9-cis-retinoic acid (9-cis-RA) was compared with two other retinoids: tretinoin and isotretinoin, in three different bladder cancer cell lines: RT4 (well differentiated), 5637 (moderately differentiated) and T24 (poorly differentiated). The three retinoids were incubated at concentrations of 0.3, 3 and 30 microg/ml with bladder cancer cells in microtitre plates for 3 and 6 days. The cytostatic effect was estimated by using luminometric measuring of ATP activity of viable cells in suspension. Compared with the older retinoids, tretinoin and isotretinoin, the highest concentration of 9-cis-RA had a cytostatic efficacy in all three bladder cancer cell lines tested. A clear dose response relationship was observed in isotretinoin-treated cultures after 6 days and in all 9-cis-RA-treated cultures. Tretinoin was either ineffective or had a stimulating effect on poorly differentiated tumour cells. To conclude, isotretinoin and 9-cis-RA had a cytostatic effect on human bladder cancer cells in vitro. However, the possibility of stimulating cancer growth at small doses, at least with tretinoin, and toxicity at high doses must be considered when planning clinical trials.

Glucocorticoid receptor beta increases migration of human bladder cancer cells.

PubMed

McBeth, Lucien; Nwaneri, Assumpta C; Grabnar, Maria; Demeter, Jonathan; Nestor-Kalinoski, Andrea; Hinds, Terry D

2016-05-10

Bladder cancer is observed worldwide having been associated with a host of environmental and lifestyle risk factors. Recent investigations on anti-inflammatory glucocorticoid signaling point to a pathway that may impact bladder cancer. Here we show an inverse effect on the glucocorticoid receptor (GR) isoform signaling that may lead to bladder cancer. We found similar GRα expression levels in the transitional uroepithelial cancer cell lines T24 and UMUC-3. However, the T24 cells showed a significant (p < 0.05) increased expression of GRβ compared to UMUC-3, which also correlated with higher migration rates. Knockdown of GRβ in the T24 cells resulted in a decreased migration rate. Mutational analysis of the 3' untranslated region (UTR) of human GRβ revealed that miR144 might positively regulate expression. Indeed, overexpression of miR144 increased GRβ by 3.8 fold. In addition, miR144 and GRβ were upregulated during migration. We used a peptide nucleic acid conjugated to a cell penetrating-peptide (Sweet-P) to block the binding site for miR144 in the 3'UTR of GRβ. Sweet-P effectively prevented miR144 actions and decreased GRβ expression, as well as the migration of the T24 human bladder cancer cells. Therefore, GRβ may have a significant role in bladder cancer, and possibly serve as a therapeutic target for the disease.

Chromium in urothelial carcinoma of the bladder.

PubMed

Golabek, Tomasz; Socha, Katarzyna; Kudelski, Jacek; Darewicz, Barbara; Markiewicz-Zukowska, Renata; Chlosta, Piotr; Borawska, Maria

2017-12-23

Many epidemiological and experimental studies report a strong role of chemical carcinogens in the etiology of bladder cancer. However, the involvement of heavy metals in tumourigenesis of urothelial carcinoma of the bladder has been poorly investigated. Therefore, the aim of this study was to examine the relationship between chromium (Cr) and bladder cancer. Chromium concentration in two 36-sample series of bladder cancer tissue and sera from patients with this neoplasm were matched with those of a control group. The amount of trace elements in every tissue sample was determined using atomic absorption spectrometry. This was correlated with tumour stage. While the median chromium concentration levels reached statistically higher values in the bladder cancer tissue, compared with the non-cancer tissue (99.632ng/g and 33.144ng/g, respectively; p<0.001), the median Cr levels in the sera of the patients with this carcinoma showed no statistical difference when compared to those of the control group (0.511μg/l and 0.710μg/l, respectively; p=0.408). The median levels of Cr in the bladder tissue, depending on the stage of the tumour, compared with the tissue without the neoplasm, observed the same relationship for both non-muscle invasive and muscle-invasive tumours (p<0.001 and p<0.01, respectively). This study shows that patients with urothelial carcinoma of the bladder had higher tissue Cr levels than people without tumour, while no difference was found in the Cr serum levels between the two groups of patients under investigation.

Association of N-acetyltransferase 1 polymorphism and bladder cancer risk: an updated meta-analysis and trial sequential analysis.

PubMed

Xu, Zicheng; Li, Xiao; Qin, Zhiqiang; Xue, Jianxin; Wang, Jingyuan; Liu, Zhentao; Cai, Hongzhou; Yu, Bin; Xu, Ting; Zou, Qin

2017-07-24

Individual studies of the association between N-acetyltransferase 1 (NAT1)*10 allele and bladder cancer susceptibility have shown inconclusive results. To derive a more precise estimation of any such relationship, we performed this systemic review and updated meta-analysis based on 17 publications. A total of 17 studies were investigated with 4,322 bladder cancer cases and 4,944 controls. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Subgroup analyses were conducted based on ethnicity, sex, source of controls and detecting methods. Then trial sequential analysis was performed to evaluate whether the evidence of the results was sufficient and reduce the risk of type I error. There was no association between NAT1*10 allele and bladder cancer risk in a random-effects model (OR = 0.96, 95% CI, 0.84-1.10) or in a fixed-effects model (OR = 0.95, 95% CI, 0.87-1.03). In addition, no significantly increased risk of bladder cancer was found in any other subgroup analysis. Then, trial sequential analyses demonstrated that the results of our study need to be further verified. Despite its limitations, the results of the present meta-analysis suggested that there was no association between NAT1*10 allele and bladder cancer risk. More importantly, our findings need to be further validated regarding whether being without the NAT1*10 allele could in the future be shown to be a potential marker for the risk of bladder cancer.

The effect of Pokemon on bladder cancer epithelial-mesenchymal transition.

PubMed

Guo, Changcheng; Zhu, Kai; Sun, Wei; Yang, Bin; Gu, Wenyu; Luo, Jun; Peng, Bo; Zheng, Junhua

2014-01-24

This study aimed at detecting Pokemon expression in bladder cancer cell and investigating the relationship between Pokemon and epithelial-mesenchymal transition. Furthermore, we investigated the functions of Pokemon in the carcinogenesis and development of bladder cancer. This study was also designed to observe the inhibitory effects of siRNA expression vector on Pokemon in bladder cancer cell. The siRNA expression vectors which were constructed to express a short hairpin RNA against Pokemon were transfected to the bladder cancer cells T24 with a liposome. Levels of Pokemon, E-cadherin and β-catenin mRNA and protein were examined by real-time quantitative-fluorescent PCR and Western blot analysis, respectively. The effects of Pokemon silencing on epithelial-mesenchymal transition of T24 cells were evaluated with wound-healing assay. Pokemon was strongly inhibited by siRNA treatment, especially siRNA3 treatment group, as it was reflected by Western blot and real-time PCR. The gene and protein of E-cadherin expression level showed increased markedly after Pokemon was inhibited by RNA interference. While there were no differences in the levels of gene and protein of β-catenin among five groups. The bladder cancer cell after Pokemon siRNA interference showed a significantly reduced wound-closing efficiency at 6, 12 and 24h. Our findings suggest Pokemon may inhibit the expression of E-cadherin. The low expression of E-cadherin lead to increasing the phenotype and apical-base polarity of epithelial cells. These changes of cells may result in the recurrence and progression of bladder cancer at last. Copyright © 2013 Elsevier Inc. All rights reserved.

Genetic variation in the base excision repair pathway and bladder cancer risk.

PubMed

Figueroa, Jonine D; Malats, Núria; Real, Francisco X; Silverman, Debra; Kogevinas, Manolis; Chanock, Stephen; Welch, Robert; Dosemeci, Mustafa; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Castaño-Vinyals, Gemma; Rothman, Nathaniel; García-Closas, Montserrat

2007-04-01

Genetic polymorphisms in DNA repair genes may impact individual variation in DNA repair capacity and alter cancer risk. In order to examine the association of common genetic variation in the base-excision repair (BER) pathway with bladder cancer risk, we analyzed 43 single nucleotide polymorphisms (SNPs) in 12 BER genes (OGG1, MUTYH, APEX1, PARP1, PARP3, PARP4, XRCC1, POLB, POLD1, PCNA, LIG1, and LIG3). Using genotype data from 1,150 cases of urinary bladder transitional cell carcinomas and 1,149 controls from the Spanish Bladder Cancer Study we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, region and smoking status. SNPs in three genes showed significant associations with bladder cancer risk: the 8-oxoG DNA glycosylase gene (OGG1), the Poly (ADP-ribose) polymerase family member 1 (PARP1) and the major gap filling polymerase-beta (POLB). Subjects who were heterozygous or homozygous variant for an OGG1 SNP in the promoter region (rs125701) had significantly decreased bladder cancer risk compared to common homozygous: OR (95%CI) 0.78 (0.63-0.96). Heterozygous or homozygous individuals for the functional SNP PARP1 rs1136410 (V762A) or for the intronic SNP POLB rs3136717 were at increased risk compared to those homozygous for the common alleles: 1.24 (1.02-1.51) and 1.30 (1.04-1.62), respectively. In summary, data from this large case-control study suggested bladder cancer risk associations with selected BER SNPs, which need to be confirmed in other study populations.

Effects of social support, hope and resilience on quality of life among Chinese bladder cancer patients: a cross-sectional study.

PubMed

Li, Meng-Yao; Yang, Yi-Long; Liu, Li; Wang, Lie

2016-05-06

Improvement of quality of life has been one of goals in health care for people living with bladder cancer. Meanwhile, positive psycho-social variables in oncology field have increasingly received attention. However, the assessment of quality of life of bladder cancer patients and the integrative effects of positive psycho-social variables has limited reporting. The aim of this study was to assess quality of life as well as the integrative effects of social support, hope and resilience on quality of life among Chinese bladder cancer patients. A cross-sectional study was conducted at the First Hospital of China Medical University in Liaoning Province, China. A total of 365 bladder cancer patients eligible for this study completed questionnaires on demographic variables, FACT-BL, Perceived Social Support Scale, Adult Hope Scale, and Resilience Scale-14 during July 2013 to July 2014. The average score of FACT-BL was 87.60 ± 16.27 (Mean ± SD). Hierarchical regression analyses indicated that social support, hope and resilience as a whole accounted for 30.3 % variance of quality of life. Under standardized estimate (β) sequence, social support, hope and resilience significantly and positively associated with quality of life, respectively. Quality of life for bladder cancer patients was at a low level in China, which should receive more attention in Chinese medical institutions. More importantly, efforts to increase social support, hope and resilience might be useful to support the quality of life among Chinese bladder cancer patients.

[THE SOMATIC MUTATIONS AND ABERRANT METHYLATION AS POTENTIAL GENETIC MARKERS OF URINARY BLADDER CANCER].

PubMed

Mikhailenko, D S; Kushlinskii, N E

2016-02-01

All around the world, more than 330 thousands cases of bladder cancer are registered annually hence representing actual problem of modern oncology. Still in demand are search and characteristic of new molecular markers of bladder cancer detecting in tumor cells from urinary sediment and having high diagnostic accuracy. The studies of last decade, especially using methods of genome-wide sequencing, permitted to receive a large amount of experimental data concerning development and progression of bladder cancer The review presents systematic analysis of publications available in PubMed data base mainly of last five years. The original studies of molecular genetic disorders under bladder cancer and meta-analyzes were considered This approach permitted to detected the most common local alterations of DNA under bladder cancer which can be detected using routine genetic methods indifferent clinical material and present prospective interest for development of test-systems. The molecular genetic markers of disease can be activating missense mutations in 7 and 10 exons of gene of receptor of growth factor of fibroblasts 3 (FGFR3), 9 and 20 exons of gene of Phosphatidylinositol-4,5-bi-phosphate-3-kinase (PIK3CA) and mutation in -124 and -146 nucleotides in promoter of gene of catalytic subunit telomerase (TERT). The development of test-systems on the basis of aberrant methylation of CpG-islets of genes-suppressors still is seemed as a difficult task because of differences in pattern of methylation of different primary tumors at various stages of clonal evolution of bladder cancer though they can be considered as potential markers.

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

PubMed Central

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. PMID:25232394

[miR-503-5p inhibits the proliferation of T24 and EJ bladder cancer cells by interfering with the Rb/E2F signaling pathway].

PubMed

Li, Xiaohui; Han, Xingtao; Yang, Jinhui; Sun, Jiantao; Wei, Pengtao

2017-10-01

Objective To observe the effect of microRNA-503-5p (miR-503-5p) on the growth of T24 and EJ bladder cancer cells, and explore the possible molecular mechanism. Methods The miR-504-5p mimics or miR-NC was transfected into T24 and EJ cells. The target gene of miR-503-5p was predicted by bioinformatics. The expressions of E2F transcription factor 3 (E2F3) mRNA and Rb/E2F signaling pathway mRNA were detected by the real-time quantitative PCR (qPCR). The expressions of Rb/E2F signal pathway proteins E2F3, cyclin E, CDK2, Rb and p-Rb were detected by Western blotting. The cell cycle of bladder cancer cell lines was determined by flow cytometry. MTT assay and plate cloning assay were performed to observe the proliferation ability of bladder cancer cells. Results After miR-503-5p mimics transfection, the expression of miR-503-5p in bladder cancer cells significantly increased. The increased expression of miR-503-5p significantly reduced the expressions of E2F3 mRNA and Rb/E2F signaling pathway mRNA in bladder cancer cells. What's more, the expressions of Rb/E2F signal pathway proteins were down-regulated. The bladder cancer cells were arrested in G0/G1 phase, and their growth was significantly inhibited by miR-503-5p. Conclusion The miR-503-5p over-expression can inhibit the growth of bladder cancer cell lines T24 and EJ by down-regulating the expression of the Rb/E2F signaling pathway.

Health information quality on the internet for bladder cancer and urinary diversion: a multi-lingual analysis.

PubMed

Corfield, Julia M; Abouassaly, Robert; Lawrentschuk, Nathan

2018-04-01

Bladder cancer patients undergoing radical cystectomy and urinary diversion are faced with difficult decisions regarding mode of urinary diversion. Although these patients may use the Internet as a guide to diagnosis and treatment options, online resources remain largely unregulated leading to a great variation in quality of medical information. Further variation in quality is seen between languages. Fortunately, tools such as an automated toolbar developed by the World Health Organization Health on the Net (HON) Foundation exist to assist physicians in recommending quality online health information to patients. We set out to compare and assess the quality of bladder cancer, ileal conduit and orthotopic neobladder web sites in 2016 on the basis of the HON principles for English language. The Google search engine imbedded with the HON toolbar was used to assess 1350 Web sites using the keywords "bladder cancer", "ileal conduit" and "orthotopic neobladder" in English, Italian and Spanish. The first 150 results of each search were identified and screened. A further analysis was completed comparing results between 2009 and 2016. Less than 20% of English, Italian and Spanish "bladder cancer" and urinary diversion ("ileal conduit" and "orthotopic neobladder") web sites are HON-accredited. HON-accredited web sites featured preferentially in the first 50 search results for bladder cancer (P=0.0001) and ileal conduit (P=0.03) web sites. Comparing 2016 results to 2009, percentage of HON-accreditation has not shown statistically significant change (-13%, P=0.23), while overall number of search results has increased (+44%). A lack of validation of bladder cancer sites is present, which is consistent across modes of urinary diversion (orthotopic neobladder and ileal conduit) and languages. It is important that physicians involved in the care of bladder cancer patients undergoing radical cystectomy and urinary diversion participate in the development of informative, ethical, and reliable health Web sites and direct patients to them.

Novel Software-Assisted Hemodynamic Evaluation of Pelvic Flow During Chemoperfusion of Pelvic Arteries for Bladder Cancer: Double- Versus Single-Balloon Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamamoto, Kiyohito, E-mail: rad105@poh.osaka-med.ac.jp; Yamamoto, Kazuhiro, E-mail: rad043@poh.osaka-med.ac.jp; Nakai, Go, E-mail: rad091@poh.osaka-med.ac.jp

2016-06-15

PurposeApproximately 83 % of patients with bladder cancer have achieved a complete response after undergoing a novel bladder preservation therapy involving balloon-occluded intra-arterial infusion chemotherapy (BOAI) using a four-lumen double-balloon catheter, known as the Osaka Medical College regimen. This study aimed to show the quantitative difference in hemodynamics of the bladder arteries using syngo iFlow (Siemens Healthcare, Erlangen, Germany), which provides an automatic tool for quantitative blood flow analysis between double BOAI (D-BOAI) and conventional single BOAI (S-BOAI).Materials and MethodsFifty patients were included. The catheters were introduced into both posterior trunks of the internal iliac arteries via contralateral femoral artery access.more » A side hole between the distal and proximal balloons was placed at the origin of each bladder artery to allow clear visualization of angiographic flow of the injected agent into the urinary bladder. Digital subtraction angiography was used during analysis with the syngo iFlow to evaluate the hemodynamics of the contrast medium in the pelvic arteries during BOAI. The comparative change in the amount of contrast medium in the bladder arteries between D-BOAI and S-BOAI was assessed using syngo iFlow.ResultsOne-hundred pelvic sides were analyzed. The amount of contrast medium in the bladder arteries using D-BOAI was more than twice that using S-BOAI (right, 3.03-fold; left, 2.81-fold).ConclusionThe amount of contrast medium in the bladder arteries using D-BOAI was higher than that using conventional S-BOAI. This may increase the anticancer drug concentration in the affected bladder, leading to a good clinical response.« less

PLK-1 Silencing in Bladder Cancer by siRNA Delivered With Exosomes.

PubMed

Greco, Kristin A; Franzen, Carrie A; Foreman, Kimberly E; Flanigan, Robert C; Kuo, Paul C; Gupta, Gopal N

2016-05-01

To use exosomes as a vector to deliver small interfering ribonucleic acid (siRNA) to silence the polo-like kinase 1 (PLK-1) gene in bladder cancer cells. Exosomes were isolated from both human embryonic kidney 293 (HEK293) cell and mesenchymal stem cell (MSC) conditioned media. Fluorescently labeled exosomes were co-cultured with bladder cancer and normal epithelial cells and uptake was quantified by image cytometry. PLK-1 siRNA and negative control siRNA were loaded into HEK293 and MSC exosomes using electroporation. An invasive bladder cancer cell line (UMUC3) was co-cultured with the electroporated exosomes. Quantitative reverse transcriptase polymerase chain reaction was performed. Protein analysis was performed by Western blot. Annexin V staining and MTT assays were used to investigate effects on apoptosis and viability. Bladder cancer cell lines internalize an increased percentage of HEK293 exosomes when compared to normal bladder epithelial cells. Treatment of UMUC3 cells with exosomes electroporated with PLK-1 siRNA achieved successful knockdown of PLK-1 mRNA and protein when compared to cells treated with negative control exosomes. HEK293 and MSC exosomes were effectively used as a delivery vector to transport PLK-1 siRNA to bladder cancer cells in vitro, resulting in selective gene silencing of PLK-1. The use of exosomes as a delivery vector for potential intravesical therapy is attractive. Copyright © 2016 Elsevier Inc. All rights reserved.

Biomarkers in patients treated with BCG: an update.

PubMed

Klap, Julia; Schmid, Marianne; Loughlin, Kevin R

2014-08-01

Bacillus Calmette-Guerin (BCG) instillations are the recommended treatment for non-muscle invasive bladder cancer but high recurrence and progression rates remain after treatment. Despite patients risk stratification, BCG effectiveness remains unpredictable. A close, invasive and expensive follow up is mandatory. To improve or even replace this heavy surveillance in this high risk population, validated biomarkers were developed. To identify the useful tools for the urologist in monitoring bladder cancer patients, we reviewed the literature focusing on plasma and urinary biomarkers of BCG-therapy outcome. Articles dated from 1988 to 2013 including specific keywords (urinary bladder neoplasm, biological markers, intravesical administration, recurrence) were examined and relevant papers were selected. Before treatment initiation, genetic polymorphisms of multiple agents (cytokines, matrix-metalloproteinases) were found to become very useful to tailor therapy and monitoring. Those biomarkers belong to personalized medicine which is a topic of great interest today, but still need to be validated in cohorts from different ethnicities. During instillations, cytokines (IL-2, IL-8, IL-6/IL-10) were reported to be reliable to determine treatment response and efficacy. Further studies are needed to confirm results and standardize thresholds. After treatment, UroVysion, the FDA-approved fluorescence in situ hybridization (FISH), appeared to be the most robust marker of all the clinical parameters reviewed; but is not yet validated for BCG-treated patients. No recommendations for everyday practice can be established today, but a combination of several markers and clinicopathological characteristics may be the future. As bladder cancer diagnosis and management are evolving, practicing urologists should be aware of and utilize bladder cancer markers in clinical practice.

SU-E-J-214: Comparative Assessment On IGRT On Partial Bladder Cancer Treatment Between CT-On-Rails (CTOR) and KV Cone Beam CT (CBCT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, T; Ma, C

2014-06-01

Purpose: Image-Guided radiation therapy(IGRT) depends on reliable online patient-specific anatomy information to address random and progressive anatomy changes. Large margins have been suggested to bladder cancer treatment due to large daily bladder anatomy variation. KV Cone beam CT(CBCT) has been used in IGRT localization prevalently; however, its lack of soft tissue contrast makes clinicians hesitate to perform daily soft tissue alignment with CBCT for partial bladder cancer treatment. This study compares the localization uncertainties of bladder cancer IGRT using CTon- Rails(CTOR) and CBCT. Methods: Three T2N0M0 bladder cancer patients (total of 66 Gy to partial bladder alone) were localized dailymore » with either CTOR or CBCT for their entire treatment course. A total of 71 sets of CTOR and 22 sets of CBCT images were acquired and registered with original planning CT scans by radiation therapists and approved by radiation oncologists for the daily treatment. CTOR scanning entailed 2mm slice thickness, 0.98mm axial voxel size, 120kVp and 240mAs. CBCT used a half fan pelvis protocol from Varian OBI system with 2mm slice thickness, 0.98axial voxel size, 125kVp, and 680mAs. Daily localization distribution was compared. Accuracy of CTOR and CBCT on partial bladder alignment was also evaluated by comparing bladder PTV coverage. Results: 1cm all around PTV margins were used in every patient except target superior limit margin to 0mm due to bowel constraint. Daily shifts on CTOR averaged to 0.48, 0.24, 0.19 mms(SI,Lat,AP directions); CBCT averaged to 0.43, 0.09, 0.19 mms(SI,Lat,AP directions). The CTOR daily localization showed superior results of V100% of PTV(102% CTOR vs. 89% CBCT) and bowel(Dmax 69.5Gy vs. 78Gy CBCT). CTOR images showed much higher contrast on bladder PTV alignment. Conclusion: CTOR daily localization for IGRT is more dosimetrically beneficial for partial bladder cancer treatment than kV CBCT localization and provided better soft tissue PTV identification.« less

Automatic staging of bladder cancer on CT urography

NASA Astrophysics Data System (ADS)

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.

The relative contributions of function, perceived psychological burden and partner support to cognitive distress in bladder cancer.

PubMed

Heyes, Susan M; Bond, Malcolm J; Harrington, Ann; Belan, Ingrid

2016-09-01

Bladder cancer is a genitourinary disease of increasing incidence. Despite improvements in treatment, outcomes remain equivocal with high recurrence rates. It is associated with poor psychosocial outcomes due to reduced functioning of the genitourinary system. The objective of these analyses was to query whether reported loss of function or the perception of psychological burden caused by this functional impedance was the key to understanding psychosocial outcomes. The sample comprised 119 participants with a confirmed diagnosis of bladder cancer. They completed a self-report questionnaire comprising the Bladder Cancer Index, Mini-mental Adjustment to Cancer Scale, Psychosocial Adjustment to Illness Scale and standard sociodemographic details. Simple mediation and serial mediation were used to explore the potential for psychological burden to mediate associations between loss of function and cognitive distress, and the potential additional contribution of positive partner support on these relationships. Age and duration of cancer were considered as covariates. Simple mediation demonstrated that the association between function and cognitive distress was fully mediated by perceived psychological burden. Serial mediation, which allowed for the addition of partner support, again demonstrated full mediation, with partner support being the key predictive variable. These analyses emphasise the importance of an appreciation of individuals' interpretation of the burden occasioned by bladder cancer and the role of a supportive partner. The implications for management discussions and support services in alleviating negative psychological outcomes in bladder cancer are highlighted. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Bladder cancer mortality and private well use in New England: An ecological study

USGS Publications Warehouse

Ayotte, J.D.; Baris, D.; Cantor, K.P.; Colt, J.; Robinson, G.R.; Lubin, J.H.; Karagas, M.; Hoover, R.N.; Fraumeni, J.F.; Silverman, D.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.

Radical cystectomy for bladder cancer: a qualitative study of patient experiences and implications for practice.

PubMed

Fitch, Margaret I; Miller, Debbie; Sharir, Sharon; McAndrew, Alison

2010-01-01

Patients being treated for bladder cancer share issues in common with other cancer patients, but also experience issues that are unique to their surgical treatment. This study used a descriptive qualitative approach to explore the experiences of patients who had undergone radical cystectomy for bladder cancer Twenty-two participants were interviewed in-depth on one occasion and were invited to attend a focus group session following the analysis of the interview transcripts. Participants described the shock of their diagnosis, their lack of information about bladder cancer, the importance of clear communication with care providers, and the types of adjustments they had to make following surgery. Specifically, changes in bodily function, body image, sexual relationships, and intimacy presented challenges for these participants. Although there was a sense of acceptance about the treatment-related events, there were still significant adjustments required by individuals following their surgery. Information, open communication, and support from family and friends were seen as important factors in helping patients adjust after surgery. Patients require clear, concise and consistent information about their cancer, treatment options, and course of care. Nurses caring for patients following surgery for bladder cancer need to understand the unique needs of these patients.

Long-term consequences from bladder perforation and/or violation in the presence of transitional cell carcinoma: results of a small series and a review of the literature.

PubMed

Mydlo, J H; Weinstein, R; Shah, S; Solliday, M; Macchia, R J

1999-04-01

Perforation of the bladder during transurethral resection is a worrisome complication for most urologists. Little is known about the consequences of seeding of tumor cells into the peritoneum or retroperitoneum. We reviewed several hospital patient databases as well as the literature to determine the outcome of such situations. We performed a local multi-institutional case and MEDLINE review using key words, such as bladder neoplasm, neoplasm seeding, perforation, rupture, transurethral resection, peritonitis and tumor. We also contacted several urologists and oncologists at major cancer centers in the United States and Europe regarding the incidence and followup of perforated/violated bladder cancer cases. There were 16 bladder violations in the presence of transitional cell carcinoma, including 2 partial cystectomies that had negative margins and no subsequent metastatic recurrences, a bladder tumor that was detected during suprapubic prostatectomy and perforations during transurethral resection (extraperitoneal in 4 cases and intraperitoneal in 9). Two patients died of sepsis and existing metastatic disease, respectively. The only recurrence among the remaining 11 patients developed after intraperitoneal bladder perforation during transurethral resection for Ta grade 2 tumor. Several anecdotal reports discussed local and distal tumor recurrences, suggesting that even superficial transitional cell carcinoma can behave aggressively if grown in an environment outside the bladder. However, these reports are rare. Any benefit of prophylactic chemotherapy was not proved. While perforation of the bladder during transurethral resection for cancer and the possibility of tumor implantation are matters of concern, our review demonstrates that few patients return with an extravesical tumor recurrence either locally or distally compared to those with a nonruptured bladder after resection. Although our patient sample is small and there are a limited number of reports in the literature, the risk of recurrence still exists and the urologist should be aware of its possibility. Since recurrences are usually rapid, they may easily manifest to the urologist at followup. However, one should also consider chest x-rays and/or computerized tomography to rule out recurrences that are not clinically obvious.

Nod for Atezolizumab in Advanced Bladder Cancer.

PubMed

2017-06-01

The FDA approved atezolizumab to treat advanced bladder cancer when cisplatin chemotherapy is contraindicated. The approval offers a potentially more effective alternative to carboplatin-based chemotherapy for frail, elderly patients. ©2017 American Association for Cancer Research.

Diesel exhaust exposure and bladder cancer risk.

PubMed

Iyer, V; Harris, R E; Wynder, E L

1990-03-01

A total of 136 cases of men with urinary bladder cancer and 272 matched hospital controls were examined for potential exposure to diesel exhaust. A lifetime occupational history was obtained for all subjects in the study and assessment of exposure to diesel exhaust was based on the job titles of the subject and self-reported exposure. The risk was assessed by odds ratios, with adjustment for confounding variables, in particular cigarette smoking. There was no evidence of elevated risk in occupations with possible or probable exposure (the ORs adjusted for smoking were 1.1. and 0.9 respectively). Truck driving alone was also not associated with elevated risk (adjusted OR = 0.5). There was a weak positive crude association with any exposure, including self-reports (OR = 1.4); however after adjustment for smoking, the estimate did not retain statistical significance (OR = 1.2, 95% CI = 0.8-2.0). This study provides little to support the hypothesis of an excess of bladder cancer risk from occupational exposure to diesel exhaust.

Nitrate in drinking water and bladder cancer: a meta-analysis.

PubMed

Wang, Weiwei; Fan, Yunzhou; Xiong, Guanglian; Wu, Jing

2012-12-01

This study examined whether exposure to nitrate in drinking water is associated with increased risk for bladder cancer by conducting a comprehensive literature research. A meta-analysis was performed with and without adjustment for confounding factors. Three groups (reference, intermediate and high groups) were established in terms of different nitrate concentrations in each included study. Separate relative risk measures were calculated for intermediate and high groups. Heterogeneity was assessed by using the Q statistics. Publication bias was evaluated by Egger's and Begg's test. Quality assessment for studies was performed by using the Newcastle-Ottawa scale. Two cohorts, two case-controls, and one ecological study were included in this study. The adjusted data showed that the combined risk ratios (RRs) were 1.13 (95% CI: 0.81 to 1.57) and 1.27 (95% CI: 0.75 to 2.15) for intermediate and high groups respectively. For unadjusted data, the corresponding RRs were 1.18 (95% CI: 0.89 to 1.57) and 1.29 (95% CI: 0.81 to 2.07). Sensitivity test indicated that results were significantly underestimated when Ward's study was included. No significant publication bias was found. There was heterogeneity among studies. The results suggested that there was no sufficient evidence that nitrate in drinking water is associated with increased risks for bladder cancer.

Gamma-Klotho exhibits multiple roles in tumor growth of human bladder cancer.

PubMed

Hori, Shunta; Miyake, Makito; Tatsumi, Yoshihiro; Morizawa, Yosuke; Nakai, Yasushi; Onishi, Sayuri; Onishi, Kenta; Iida, Kota; Gotoh, Daisuke; Tanaka, Nobumichi; Fujimoto, Kiyohide

2018-04-13

Alpha-Klotho (KLα) and beta-Klotho (KLβ) have recently been reported to correlate with cancer prognosis in some malignancies and we previously reported the association between KLα, KLβ, and urothelial carcinoma of the bladder (UCB), indicating that KLβ acts as a tumor promoter. However, the association between gamma-Klotho (KLγ) and cancer prognosis remains unclear. In the present study, we evaluated the association between KLγ and UCB. To evaluate the effect of KLγ on human bladder cancer cell lines in vitro assays were performed. Exogenous KLγ increased the ability of human bladder cancer cells to proliferate, migrate, invade, form colonies, and provide anchorage-independent growth potential. In in vivo assays, eighteen mice bearing xenografts inoculated using UM-UC-3, were randomly divided into three groups and treated with a small interfering RNA (siRNA) by intratumoral administration once a week for four weeks. Knockdown of KLγ with siRNA led to a dramatic change in tumor growth and suggested that KLγ had effects on tumor growth, including promotion of cell proliferation, inhibition of apoptosis, and enhancement of the epithelial-mesenchymal transition. To confirm the study, human tissue samples were used and patients were divided into two groups according to KLγ expression level. High expression of KLγ was significantly associated with higher stage and grade cancer and the presence of lymphovascular invasion compared to patients with lower expression of KLγ. Our results suggest that KLγ plays an important role in tumor invasion and progression and these results may lead to the development of new therapies and diagnostic methods for UCB.

Gamma-Klotho exhibits multiple roles in tumor growth of human bladder cancer

PubMed Central

Hori, Shunta; Miyake, Makito; Tatsumi, Yoshihiro; Morizawa, Yosuke; Nakai, Yasushi; Onishi, Sayuri; Onishi, Kenta; Iida, Kota; Gotoh, Daisuke; Tanaka, Nobumichi; Fujimoto, Kiyohide

2018-01-01

Alpha-Klotho (KLα) and beta-Klotho (KLβ) have recently been reported to correlate with cancer prognosis in some malignancies and we previously reported the association between KLα, KLβ, and urothelial carcinoma of the bladder (UCB), indicating that KLβ acts as a tumor promoter. However, the association between gamma-Klotho (KLγ) and cancer prognosis remains unclear. In the present study, we evaluated the association between KLγ and UCB. To evaluate the effect of KLγ on human bladder cancer cell lines in vitro assays were performed. Exogenous KLγ increased the ability of human bladder cancer cells to proliferate, migrate, invade, form colonies, and provide anchorage-independent growth potential. In in vivo assays, eighteen mice bearing xenografts inoculated using UM-UC-3, were randomly divided into three groups and treated with a small interfering RNA (siRNA) by intratumoral administration once a week for four weeks. Knockdown of KLγ with siRNA led to a dramatic change in tumor growth and suggested that KLγ had effects on tumor growth, including promotion of cell proliferation, inhibition of apoptosis, and enhancement of the epithelial-mesenchymal transition. To confirm the study, human tissue samples were used and patients were divided into two groups according to KLγ expression level. High expression of KLγ was significantly associated with higher stage and grade cancer and the presence of lymphovascular invasion compared to patients with lower expression of KLγ. Our results suggest that KLγ plays an important role in tumor invasion and progression and these results may lead to the development of new therapies and diagnostic methods for UCB. PMID:29731962

Polymorphic Expression of a Human Superficial Bladder Tumor Antigen Defined by Mouse Monoclonal Antibodies

NASA Astrophysics Data System (ADS)

Fradet, Yves; Islam, Nazrul; Boucher, Lucie; Parent-Vaugeois, Carmen; Tardif, Marc

1987-10-01

Three mouse monoclonal antibodies (mAbs), which define a highly restricted antigen, were obtained by simultaneous immunizations with superficial papillary bladder tumor cells and mouse polyclonal serum against normal urothelium. The antigen was detected by the avidin/biotin/peroxidase method in 30/44 superficial bladder tumors (68%) but in only 4/27 infiltrating urothelial cancers (with much less intensity). No normal adult or fetal tissues tested expressed the antigen, including normal urothelium from 40 individuals, 13 of whom had a bladder tumor positive for the antigen. Only 1 of 45 nonbladder tumors showed some reactivity with one of the three mAbs. Serological tests on a large panel of human cancer cell lines and normal cultured cells were negative. The antigen is highly stable and well preserved on paraffin-embedded tissues. Electrophoretic transfer blot experiments with fresh tumor extracts showed that all three mAbs react with a determinant on a component of 300,000 Mr (pI 9.5) and 62,000 Mr (pI 6.5). The antigen shows polymorphic expression at the cellular level on tissue sections and also at a molecular level on immunoblots where the two bands are differentially detected on extracts of a series of tumors but are not visualized on normal urothelium extracts. The characteristics of this antigenic system suggest that it may provide some insights about the biology of bladder cancer. Specific detection of the antigen on 70% of superficial bladder tumors with normal cytology may be useful for their diagnosis and follow-up.

Disulfide-crosslinked nanomicelles confer cancer-specific drug delivery and improve efficacy of paclitaxel in bladder cancer

NASA Astrophysics Data System (ADS)

Pan, Amy; Zhang, Hongyong; Li, Yuanpei; Lin, Tzu-yin; Wang, Fuli; Lee, Joyce; Cheng, Mingshan; Dall'Era, Marc; Li, Tianhong; deVere White, Ralph; Pan, Chong-Xian; Lam, Kit S.

2016-10-01

Chemotherapy commonly used in the treatment of advanced bladder cancer is only moderately effective and associated with significant toxicity. There has been no appreciable improvement in overall survival over the last three decades. The goal of this project is to develop and characterize bladder cancer-specific nanometer-scale micelles loaded with the chemotherapeutic drug paclitaxel (PTX) and determine the anti-tumor activity and toxicity. Micelle-building-material telodendrimers were synthesized through the stepwise conjugation of eight cholic acid units at one terminus of polyethylene glycol (PEG) and a bladder cancer-specific targeting peptide named PLZ4 at the other terminus. To synthesize disulfide-crosslinked PLZ4 nanomicelles (DC-PNM), cysteine was introduced between the cholic acid and PEG. DC-PNM-PTX was synthesized through the evaporation method by loading PTX in the core. The loading capacity of PTX in DC-PNM was 25% (W/W). The loading efficiency was over 99%. DC-PNM-PTX was spherical with the median size of 25 nm. The stability of DC-PNM-PTX was determined in a solution containing sodium docecyl sulfate (SDS). It was stable in a SDS solution, but dissolved within 5 min after the addition of glutathione at the physiological intracellular concentration of 10 mM. In vivo targeting and anti-tumor activity were determined in immunodeficient mice carrying patient-derived bladder cancer xenografts (PDXs). After intravenous administration, DC-PNM specifically targeted the bladder cancer PDXs, but very little to the lung cancer xenografts in the same mice (p < 0.001). DC-PNM loaded with PTX overcame cisplatin resistance, and improved the median survival from 55 d with free PTX to 69.5 d (p = 0.03) of mice carrying PDXs. In conclusion, DC-PNM remained stable in the SDS solution, specifically targeted the bladder cancer xenografts in vivo, and improved the anti-cancer efficacy of PTX.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, JY; Hong, DL

Purpose: To investigate the impact of bladder filling status of the organs at risk (OARs) on dose distribution during intensity modulated radiotherapy (IMRT) for cervical cancer patients. Methods: Twelve cervical cancer patients treated with IMRT were selected for this study. The prescription dose was 45Gy/25 fractions with the 6 MV photon beam. All patients performed two CT scans, one with an empty bladder, the other one with bladder filled. For the registration of two CT scans, the fusion was automatically carried out upon the bony anatomy. The OARs (bladder, rectum, pelvic bone and small intestine) were delineated to planning CTmore » to evaluate the dose distributions. These dose distributions were compared between empty bladder and bladder filling. Results: The bladder volume with empty bladder and bladder filling was 403.2±124.13cc and 101.4±87.5cc, respectively. There were no statistical differences between empty bladder and bladder filling in the mean value of pelvic bone V10Gy, V20Gy, V40Gy; rectum V40Gy and V45Gy. The bladder V40Gy and V45Gy were lower in the bladder filling group than in the empty bladder group (63.7%±5.8% vs 87.5%±7.8%, 45.1%±9.5% vs 62.4%±11.8%, respectively). The V45Gy for small intestine in the bladder filling group was significantly less than the empty bladder group (146.7cc±95.3cc vs 245.7cc±101.8cc). Conclusion: Our study finds that the bladder filling status did not have a significant impact on dose distribution in the rectum and pelvic bone. However, the changes of bladder filling have a large impact on bladder and small intestine doses. A full bladder is strongly recommended during treatment for cervical cancer patients.« less

Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study

PubMed Central

Michaud, D S; Pietinen, P; Taylor, P R; Virtanen, M; Virtamo, J; Albanes, D

2002-01-01

We examined the relation between dietary fruit and vegetables, carotenoids and vitamin intakes and the risk of bladder cancer among male smokers in a prospective cohort study. Over a median of 11 years, we followed 27 111 male smokers aged 50–69 years who were initially enrolled in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. During this period, 344 men developed bladder cancer. All of these men had completed a 276-food item dietary questionnaire at baseline. Cox proportional hazards models were used to estimate the relative risks and 95% confidence intervals and to simultaneously adjust for age, smoking history, energy intake and intervention group. Consumption of fruits and vegetables was not associated with the risk of bladder cancer (relative risk=1.28; 95% confidence intervals CI: 0.89–1.84, for highest vs lowest quintile). Similarly, no associations were observed for groups of fruits or vegetables (berries and cruciferous vegetables), or for specific fruits and vegetables. Dietary intakes of alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin, beta-cryptoxanthin, vitamins A, E, and C, and folate were not related to the risk of bladder cancer. These findings suggest that fruit and vegetable intakes are not likely to be associated with bladder cancer risk. However, these results may not be generalisable to non-smokers. British Journal of Cancer (2002) 87, 960–965. doi:10.1038/sj.bjc.6600604 www.bjcancer.com © 2002 Cancer Research UK PMID:12434284

Cyclin D1 Downregulation Contributes to Anti-Cancer Effect of Isorhapontigenin (ISO) on Human Bladder Cancer Cells

PubMed Central

Fang, Yong; Cao, Zipeng; Hou, Qi; Ma, Chen; Yao, Chunsuo; Li, Jingxia; Wu, Xue-Ru; Huang, Chuanshu

2013-01-01

Isorhapontigenin (ISO) is a new derivative of stilbene compound that was isolated from the Chinese herb Gnetum Cleistostachyum, and has been used for treatment of bladder cancers for centuries. In our current studies, we have explored the potential inhibitory effect and molecular mechanisms underlying ISO anti-cancer effects on anchorage-independent growth of human bladder cancer cell lines. We found that ISO showed a significant inhibitory effect on human bladder cancer cell growth and was accompanied with related cell cycle G0/G1 arrest as well as downregulation of Cyclin D1 expression at the transcriptional level in UMUC3 and RT112 cells. Further studies identified that ISO down-regulated Cyclin D1 gene transcription via inhibition of SP1 transactivation. Moreover, ectopic expression of GFP-Cyclin D1 rendered UMUC3 cells resistant to induction of cell cycle G0/G1 arrest and inhibition of cancer cell anchorage-independent growth by ISO treatment. Together, our studies demonstrate that ISO is an active compound that mediates for Gnetum Cleistostachyum’s induction of cell cycle G0/G1 arrest and inhibition of cancer cell anchorage-independent growth through down-regulating SP1/Cyclin D1 axis in bladder cancer cells. Our studies provide a novel insight into understanding the anti-cancer activity of the Chinese herb Gnetum Cleistostachyum and its isolate ISO. PMID:23723126

Unmasking molecular profiles of bladder cancer.

PubMed

Piao, Xuan-Mei; Byun, Young Joon; Kim, Wun-Jae; Kim, Jayoung

2018-03-01

Precision medicine is designed to tailor treatments for individual patients by factoring in each person's specific biology and mechanism of disease. This paradigm shifted from a "one size fits all" approach to "personalized and precision care" requires multiple layers of molecular profiling of biomarkers for accurate diagnosis and prediction of treatment responses. Intensive studies are also being performed to understand the complex and dynamic molecular profiles of bladder cancer. These efforts involve looking bladder cancer mechanism at the multiple levels of the genome, epigenome, transcriptome, proteome, lipidome, metabolome etc. The aim of this short review is to outline the current technologies being used to investigate molecular profiles and discuss biomarker candidates that have been investigated as possible diagnostic and prognostic indicators of bladder cancer.

A case-control study of diesel exhaust exposure and bladder cancer.

PubMed

Wynder, E L; Dieck, G S; Hall, N E; Lahti, H

1985-08-01

The relationship between bladder cancer and employment in occupations involving exposure to diesel exhaust was examined using data from a hospital-based case-control study of men aged 20 to 80 years in 18 hospitals in six U.S. cities, from January 1981 to May 1983. In this analysis, 194 cases and 582 controls were compared according to occupation, smoking history, alcohol and coffee consumption, and various demographic variables. No difference was found in the proportion of bladder cancer cases employed in occupations with exposure to diesel exhaust compared to controls. This relationship did not change after taking smoking habits into account. Bladder cancer cases were significantly more likely to be current smokers of cigarettes than were controls.

Factors associated with suicide in patients with genitourinary malignancies.

PubMed

Klaassen, Zachary; Jen, Rita P; DiBianco, John M; Reinstatler, Lael; Li, Qiang; Madi, Rabii; Lewis, Ronald W; Smith, Arthur M; Neal, Durwood E; Moses, Kelvin A; Terris, Martha K

2015-06-01

Approximately 70% of all suicides in patients aged >60 years are attributed to physical illness, with higher rates noted in patients with cancer. The purpose of the current study was to characterize suicide rates among patients with genitourinary cancers and identify factors associated with suicide in this specific cohort. Patients with prostate, bladder, kidney, testis, and penile cancer were identified in the Surveillance, Epidemiology, and End Results database (1988-2010). Standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs) were calculated for each anatomic site. Multivariable logistic regression models generated odds ratios (ORs) for the identification of factors associated with suicide for each malignancy. There were 2268 suicides identified among 1,239,522 individuals with genitourinary malignancies observed for 7,307,377 person-years. The SMRs for patients with cancer were 1.37 for prostate cancer (95% CI, 0.99-1.86), 2.71 for bladder cancer (95% CI, 2.02-3.62), 1.86 for kidney cancer (95% CI, 1.32-2.62), 1.23 for testis cancer (95% CI, 0.88-1.73), and 0.95 for penile cancer (95% CI, 0.65-1.35). On multivariable analysis, male sex was found to be associated with odds of suicide among patients with bladder cancer (OR, 6.63) and kidney cancer (OR, 4.98). Increasing age was associated with suicide for patients with prostate, bladder, and testis cancer (OR range, 1.03-1.06). Distant disease was associated with suicide in patients with prostate, bladder, and kidney cancer (OR range, 2.82-5.43). Among patients with prostate, bladder, and kidney cancer, African American patients were less likely to commit suicide compared with white individuals (OR range, 0.26-0.46). Suicide in patients with genitourinary malignancies poses a public health dilemma, especially among men, the elderly, and those with aggressive disease. Clinicians should be aware of risk factors for suicide in these patients. © 2015 American Cancer Society.

Quantitative diagnosis of bladder cancer by morphometric analysis of HE images

NASA Astrophysics Data System (ADS)

Wu, Binlin; Nebylitsa, Samantha V.; Mukherjee, Sushmita; Jain, Manu

2015-02-01

In clinical practice, histopathological analysis of biopsied tissue is the main method for bladder cancer diagnosis and prognosis. The diagnosis is performed by a pathologist based on the morphological features in the image of a hematoxylin and eosin (HE) stained tissue sample. This manuscript proposes algorithms to perform morphometric analysis on the HE images, quantify the features in the images, and discriminate bladder cancers with different grades, i.e. high grade and low grade. The nuclei are separated from the background and other types of cells such as red blood cells (RBCs) and immune cells using manual outlining, color deconvolution and image segmentation. A mask of nuclei is generated for each image for quantitative morphometric analysis. The features of the nuclei in the mask image including size, shape, orientation, and their spatial distributions are measured. To quantify local clustering and alignment of nuclei, we propose a 1-nearest-neighbor (1-NN) algorithm which measures nearest neighbor distance and nearest neighbor parallelism. The global distributions of the features are measured using statistics of the proposed parameters. A linear support vector machine (SVM) algorithm is used to classify the high grade and low grade bladder cancers. The results show using a particular group of nuclei such as large ones, and combining multiple parameters can achieve better discrimination. This study shows the proposed approach can potentially help expedite pathological diagnosis by triaging potentially suspicious biopsies.

Prostaglandin receptors EP1-4 as a potential marker for clinical outcome in urothelial bladder cancer.

PubMed

von der Emde, Laura; Goltz, Diane; Latz, Stefan; Müller, Stefan C; Kristiansen, Glen; Ellinger, Jörg; Syring, Isabella

2014-01-01

Prostaglandins, especially prostaglandin E2 (PGE2), and COX-2 play an important role in carcinogenesis of many tumors including bladder cancer (BCA). The PGE2 receptors EP1-4 regulate tumor cell growth, invasion and migration in different tumor entities but EP expression in BCA remains to be determined. In the present study we examined the expression of EP1-4 in non-muscle invasive bladder cancer (NMIBC), muscle invasive bladder cancer (MIBC) and normal urothelial tissue (NU) using immunohistochemistry. Nuclear and cytoplasmic EP1-4 expression was correlated with clinicopathological parameters and survival of BCA patients. EP1, EP2 and EP3 were significantly less expressed in the cytoplasm und nucleus of NMIBC and MIBC than in NU; EP4 cytoplasmic staining in MIBC was significantly higher compared to NU. The cytoplasmic staining was significantly more abundant in MIBC than in NMIBC in all investigated receptors except EP2. The level of EP staining in NMIBC was correlated with staging and grading, especially cytoplasmic EP1. Nuclear staining of EP1 was an independent predictor of BCA recurrence-free survival in NMIBC patients. EP receptors are dysregulated in BCA. The increase of EP1 may be used as prognostic parameter in NMIBC patients and its dysregulation could be targeted by specific EP1 inhibitors.

Prostaglandin receptors EP1-4 as a potential marker for clinical outcome in urothelial bladder cancer

PubMed Central

von der Emde, Laura; Goltz, Diane; Latz, Stefan; Müller, Stefan C; Kristiansen, Glen; Ellinger, Jörg; Syring, Isabella

2014-01-01

Prostaglandins, especially prostaglandin E2 (PGE2), and COX-2 play an important role in carcinogenesis of many tumors including bladder cancer (BCA). The PGE2 receptors EP1-4 regulate tumor cell growth, invasion and migration in different tumor entities but EP expression in BCA remains to be determined. In the present study we examined the expression of EP1-4 in non-muscle invasive bladder cancer (NMIBC), muscle invasive bladder cancer (MIBC) and normal urothelial tissue (NU) using immunohistochemistry. Nuclear and cytoplasmic EP1-4 expression was correlated with clinicopathological parameters and survival of BCA patients. EP1, EP2 and EP3 were significantly less expressed in the cytoplasm und nucleus of NMIBC and MIBC than in NU; EP4 cytoplasmic staining in MIBC was significantly higher compared to NU. The cytoplasmic staining was significantly more abundant in MIBC than in NMIBC in all investigated receptors except EP2. The level of EP staining in NMIBC was correlated with staging and grading, especially cytoplasmic EP1. Nuclear staining of EP1 was an independent predictor of BCA recurrence-free survival in NMIBC patients. EP receptors are dysregulated in BCA. The increase of EP1 may be used as prognostic parameter in NMIBC patients and its dysregulation could be targeted by specific EP1 inhibitors. PMID:25520883

Nitrate from Drinking Water and Diet and Bladder Cancer Among Postmenopausal Women in Iowa

PubMed Central

Jones, Rena R.; Weyer, Peter J.; DellaValle, Curt T.; Inoue-Choi, Maki; Anderson, Kristin E.; Cantor, Kenneth P.; Krasner, Stuart; Robien, Kim; Freeman, Laura E. Beane; Silverman, Debra T.; Ward, Mary H.

2016-01-01

Background: Nitrate is a drinking water contaminant arising from agricultural sources, and it is a precursor in the endogenous formation of N-nitroso compounds (NOC), which are possible bladder carcinogens. Objectives: We investigated the ingestion of nitrate and nitrite from drinking water and diet and bladder cancer risk in women. Methods: We identified incident bladder cancers among a cohort of 34,708 postmenopausal women in Iowa (1986–2010). Dietary nitrate and nitrite intakes were estimated from a baseline food frequency questionnaire. Drinking water source and duration were assessed in a 1989 follow-up. For women using public water supplies (PWS) > 10 years (n = 15,577), we estimated average nitrate (NO3-N) and total trihalomethane (TTHM) levels and the number of years exceeding one-half the maximum contaminant level (NO3-N: 5 mg/L, TTHM: 40 μg/mL) from historical monitoring data. We computed hazard ratios (HRs) and 95% confidence intervals (CIs), and assessed nitrate interactions with TTHM and with modifiers of NOC formation (smoking, vitamin C). Results: We identified 258 bladder cancer cases, including 130 among women > 10 years at their PWS. In multivariable-adjusted models, we observed nonsignificant associations among women in the highest versus lowest quartile of average drinking water nitrate concentration (HR = 1.48; 95% CI: 0.92, 2.40; ptrend = 0.11), and we found significant associations among those exposed ≥ 4 years to drinking water with > 5 mg/L NO3-N (HR = 1.62; 95% CI: 1.06, 2.47; ptrend = 0.03) compared with women having 0 years of comparable exposure. TTHM adjustment had little influence on associations, and we observed no modification by vitamin C intake. Relative to a common reference group of never smokers with the lowest nitrate exposures, associations were strongest for current smokers with the highest nitrate exposures (HR = 3.67; 95% CI: 1.43, 9.38 for average water NO3-N and HR = 3.48; 95% CI: 1.20, 10.06 and ≥ 4 years > 5 mg/L, respectively). Dietary nitrate and nitrite intakes were not associated with bladder cancer. Conclusions: Long-term ingestion of elevated nitrate in drinking water was associated with an increased risk of bladder cancer among postmenopausal women. Citation: Jones RR, Weyer PJ, DellaValle CT, Inoue-Choi M, Anderson KE, Cantor KP, Krasner S, Robien K, Beane Freeman LE, Silverman DT, Ward MH. 2016. Nitrate from drinking water and diet and bladder cancer among postmenopausal women in Iowa. Environ Health Perspect 124:1751–1758; http://dx.doi.org/10.1289/EHP191 PMID:27258851

Monoclonal antibody Zt/g4 targeting RON receptor tyrosine kinase enhances chemosensitivity of bladder cancer cells to Epirubicin by promoting G1/S arrest and apoptosis.

PubMed

Chen, Jun-Feng; Yu, Bi-Xia; Yu, Rui; Ma, Liang; Lv, Xiu-Yi; Cheng, Yue; Ma, Qi

2017-02-01

Epirubicin (EPI) is one of the most used intravesical chemotherapy agents after transurethral resection to non-muscle invasive bladder tumors (NMIBC) to prevent cancer recurrence and progression. However, even after resection of bladder tumors and intravesical chemotherapy, half of them will recur and progress. RON is a membrane tyrosine kinase receptor usually overexpressed in bladder cancer cells and associated with poor pathological features. This study aims to investigate the effects of anti-RON monoclonal antibody Zt/g4 on the chemosensitivity of bladder cells to EPI. After Zt/g4 treatment, cell cytotoxicity was significantly increased and cell invasion was markedly suppressed in EPI-treated bladder cancer cells. Further investigation indicated that combing Zt/g4 with EPI promoted cell G1/S-phase arrest and apoptosis, which are the potential mechanisms that RON signaling inhibition enhances chemosensitivity of EPI. Thus, combing antibody-based RON targeted therapy enhances the therapeutic effects of intravesical chemotherapy, which provides new strategy for further improvement of NMIBC patient outcomes.