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Sample records for bladder cancer detection

  1. Noninvasive Electromagnetic Detection of Bladder Cancer

    PubMed Central

    Cormio, Luigi; Vedruccio, Clarbruno; Leucci, Giorgio; Massenio, Paolo; Di Fino, Giuseppe; Cavaliere, Vincenzo; Carrieri, Giuseppe

    2014-01-01

    Objectives. Normal and neoplastic human tissues have different electromagnetic properties. This study aimed to determine the diagnostic accuracy of noninvasive electromagnetic detection of bladder cancer (BC) by the tissue-resonance interaction method (TRIM-prob). Patients and Methods. Consecutive patients were referred for cystoscopy because of (i) microscopic or gross hematuria and/or irritative voiding symptoms and (ii) bladder ultrasounds and urinary cytology findings negative or just suspicious of malignancy. Patients were first submitted to TRIM-prob bladder scanning by a single investigator and then to cystoscopy by another investigator blind to TRIM-prob data. Results. In 125 evaluated patients cystoscopy was positive for BC in 47 and negative in the remaining 78; conversely, TRIM-prob bladder scanning was positive for BC in 53 and negative in 72. In particular, TRIM-prob scanning yielded 7 false positives and only one false negative; therefore, its overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 97.9%, 89.9%, 86.8%, 98.6%, and 93.6%, respectively. Conclusions. TRIM-prob bladder scanning was a simple and quite accurate method for non-invasive electromagnetic detection of BC. If the elevated positive and negative predictive values will be replicated in further well-designed studies, it could be used to screen asymptomatic patients at high risk of BC. PMID:24563795

  2. Fluorescence detection of bladder cancer: a review.

    PubMed

    D'Hallewin, Marie-Ange; Bezdetnaya, Lina; Guillemin, François

    2002-11-01

    An effective therapeutic outcome in the treatment of bladder cancer is largely defined by its early detection. In this context, big expectations have been placed on the fluorescence-guided diagnosis of bladder cancer. This paper reviews the applications of endo- and exogenous fluorescence for early diagnosis of in situ carcinoma of the bladder. Despite certain advantages of autofluorescence, exogenous fluorescence, based on the intravesical instillation of fluorophores with the following visible light excitation, has been shown to be more effective in terms of sensitivity and specificity for detecting carcinoma in situ. The equipment consists of a slightly modified light source in order to choose between white (conventional endoscopy) or blue light (fluorescence endoscopy) excitation, and specific lenses, in order to enhance maximally the contrast between normal (blue) autofluorescence and red fluorescence from malignancies. Among exogenous fluorophores, a particular emphasis will be put on the 5-aminolevulinic acid (ALA), its ester derivative (h-ALA) and hypericin. These dyes demonstrated an excellent sensitivity above 90% and specificity ranging from 70% to 90%.

  3. Bladder cancer

    MedlinePlus

    Transitional cell carcinoma of the bladder; Urothelial cancer ... In the United States, bladder cancer often starts from the cells lining the bladder. These cells are called transitional cells. These tumors are classified by the way ...

  4. Rationale for an early detection program for bladder cancer

    PubMed Central

    Khochikar, Makarand V.

    2011-01-01

    Introduction: A total of 356,557 new cases were diagnosed annually worldwide in 2009, it was estimated that 52,810 new patients were to be diagnosed with bladder cancer and there were 10,180 projected deaths from the disease in the USA. Despite being the fourth commonest cancer in men, we do not have an early detection/screening program for bladder cancer. The review was aimed at looking at the evidence for the rationale for an early detection program for bladder cancer. Materials and Methods: A detailed search on bladder cancer epidemiology, diagnosis, pathology, tumor markers, treatment outcomes, screening, morbidity and mortality of bladder cancer was carried out on Pubmed central/Medline. Original articles, review articles, monograms, book chapters on bladder cancer, text books on urological oncology, oncology and urology were reviewed. The latest information for new articles before publication was last accessed in June 2010. Discussion and Conclusions: Bladder cancer is the fourth commonest cancer in men, the annual death rate from this disease is significant and every year there is an increase in its incidence globally. The prognosis of bladder cancer is stage and grade dependent; the lower the stage (T2 or less) the better is the survival. Delay in the diagnosis and treatment does alter the overall outcome. Therefore, there is a clear need for early detection of bladder cancer and screening program. Although we do not have an ideal marker for bladder cancer, it is time we maximize the potential of markers such as UroVysion, NMP22 along with cytology to start such a program. May be as a first step the early detection and screening program could be started in high-risk population. It is not worth waiting till we find the best marker as it would be unfair to our patients. The fear of unnecessary tests and treatment in bladder cancer after its detection in screening program is without any substance. The cost-effectiveness of such a program is certainly

  5. Bladder cancer.

    PubMed Central

    Leung, H. Y.; Griffiths, T. R.; Neal, D. E.

    1996-01-01

    Bladder cancer is the fourth most common cancer in England and Wales. The most common presenting symptom is macroscopic haematuria. The management options for superficial and invasive bladder cancer depend on the stage at presentation. Most superficial bladder cancers are managed by transurethral resection and cytoscopic follow-up. The prognosis for patients with invasive bladder cancer is less good. The role of chemical, radiotherapeutic and surgical intervention are discussed. PMID:9015464

  6. Detection of Bladder Cancer Using Proteomic Profiling of Urine Sediments

    PubMed Central

    Majewski, Tadeusz; Spiess, Philippe E.; Bondaruk, Jolanta; Black, Peter; Clarke, Charlotte; Benedict, William; Dinney, Colin P.; Grossman, Herbert Barton; Tang, Kuang S.; Czerniak, Bogdan

    2012-01-01

    We used protein expression profiles to develop a classification rule for the detection and prognostic assessment of bladder cancer in voided urine samples. Using the Ciphergen PBS II ProteinChip Reader, we analyzed the protein profiles of 18 pairs of samples of bladder tumor and adjacent urothelium tissue, a training set of 85 voided urine samples (32 controls and 53 bladder cancer), and a blinded testing set of 68 voided urine samples (33 controls and 35 bladder cancer). Using t-tests, we identified 473 peaks showing significant differential expression across different categories of paired bladder tumor and adjacent urothelial samples compared to normal urothelium. Then the intensities of those 473 peaks were examined in a training set of voided urine samples. Using this approach, we identified 41 protein peaks that were differentially expressed in both sets of samples. The expression pattern of the 41 protein peaks was used to classify the voided urine samples as malignant or benign. This approach yielded a sensitivity and specificity of 59% and 90%, respectively, on the training set and 80% and 100%, respectively, on the testing set. The proteomic classification rule performed with similar accuracy in low- and high-grade bladder carcinomas. In addition, we used hierarchical clustering with all 473 protein peaks on 65 benign voided urine samples, 88 samples from patients with clinically evident bladder cancer, and 127 samples from patients with a history of bladder cancer to classify the samples into Cluster A or B. The tumors in Cluster B were characterized by clinically aggressive behavior with significantly shorter metastasis-free and disease-specific survival. PMID:22879988

  7. Detection of bladder cancer using proteomic profiling of urine sediments.

    PubMed

    Majewski, Tadeusz; Spiess, Philippe E; Bondaruk, Jolanta; Black, Peter; Clarke, Charlotte; Benedict, William; Dinney, Colin P; Grossman, Herbert Barton; Tang, Kuang S; Czerniak, Bogdan

    2012-01-01

    We used protein expression profiles to develop a classification rule for the detection and prognostic assessment of bladder cancer in voided urine samples. Using the Ciphergen PBS II ProteinChip Reader, we analyzed the protein profiles of 18 pairs of samples of bladder tumor and adjacent urothelium tissue, a training set of 85 voided urine samples (32 controls and 53 bladder cancer), and a blinded testing set of 68 voided urine samples (33 controls and 35 bladder cancer). Using t-tests, we identified 473 peaks showing significant differential expression across different categories of paired bladder tumor and adjacent urothelial samples compared to normal urothelium. Then the intensities of those 473 peaks were examined in a training set of voided urine samples. Using this approach, we identified 41 protein peaks that were differentially expressed in both sets of samples. The expression pattern of the 41 protein peaks was used to classify the voided urine samples as malignant or benign. This approach yielded a sensitivity and specificity of 59% and 90%, respectively, on the training set and 80% and 100%, respectively, on the testing set. The proteomic classification rule performed with similar accuracy in low- and high-grade bladder carcinomas. In addition, we used hierarchical clustering with all 473 protein peaks on 65 benign voided urine samples, 88 samples from patients with clinically evident bladder cancer, and 127 samples from patients with a history of bladder cancer to classify the samples into Cluster A or B. The tumors in Cluster B were characterized by clinically aggressive behavior with significantly shorter metastasis-free and disease-specific survival.

  8. Biomarkers for detection and surveillance of bladder cancer

    PubMed Central

    Budman, Lorne I; Kassouf, Wassim; Steinberg, Jordan R

    2008-01-01

    Introduction Bladder cancer is the fourth most common cancer in men and the ninth most common cancer in women in Canada. Early detection of tumours is essential for improved prognosis and long-term survival. The standard method for detection and surveillance is cystoscopy together with urine cytology. Cystoscopy is relatively sensitive but is expensive and invasive. Urinary cytology is a noninvasive method that has poor sensitivity but high specificity; it is relied on for the detection of carcinoma in situ. Currently, several urinary-based bladder tumour biomarkers with USFDA/Health Canada approval are available commercially, but none have been widely adopted by urologists despite their offering high sensitivity and/or specificity. We present here a review of recent studies evaluating 7 commercial biomarker assays for the detection and/or surveillance of bladder cancer. Results Sensitivity and specificity ranges, respectively, for each marker were reported as follows: BTA Stat (Polymedco), 52.5%–78.0% and 69.0%–87.1%; BTA Trak (Polymedco), 51%–100% and 73%–92.5%; cytology, 12.1%–84.6% and 78.0%–100%; hematuria dipstick, 47.0%–92.6% and 51.0%–84.0%; NMP22 Bladder Cancer Test (Matritech), 34.6%–100% and 60.0%–95.0%; NMP22 BladderChek (Matritech), 49.5%–65.0% and 40.0%–89.8%; ImmunoCyt/uCyt+ (DiagnoCure), 63.3%–84.9% and 62.0%–78.1%; ImmunoCyt/uCyt+ and cytology, 81.0%–89.3% and 61.0%–77.7%; and UroVysion (Abbott Molecular)/florescence in situ hybridization, 68.6%–100% and 65.0%–96.0%. Conclusion We find that no currently available bladder cancer urinary marker is sensitive enough to eliminate the need for cystoscopy. In addition, cytology remains integral to the detection of occult cancer. However, owing to their relatively high sensitivities, these markers may be used to extend the period between cystoscopies in the surveillance of patients with transitional cell carcinoma. Further study is required to determine which markers

  9. Bladder cancer.

    PubMed

    Sanli, Oner; Dobruch, Jakub; Knowles, Margaret A; Burger, Maximilian; Alemozaffar, Mehrdad; Nielsen, Matthew E; Lotan, Yair

    2017-04-13

    Bladder cancer is a highly prevalent disease and is associated with substantial morbidity, mortality and cost. Environmental or occupational exposures to carcinogens, especially tobacco, are the main risk factors for bladder cancer. Most bladder cancers are diagnosed after patients present with macroscopic haematuria, and cases are confirmed after transurethral resection of bladder tumour (TURBT), which also serves as the first stage of treatment. Bladder cancer develops via two distinct pathways, giving rise to non-muscle-invasive papillary tumours and non-papillary (solid) muscle-invasive tumours. The two subtypes have unique pathological features and different molecular characteristics. Indeed, The Cancer Genome Atlas project identified genetic drivers of muscle-invasive bladder cancer (MIBC) as well as subtypes of MIBC with distinct characteristics and therapeutic responses. For non-muscle-invasive bladder cancer (NMIBC), intravesical therapies (primarily Bacillus Calmette-Guérin (BCG)) with maintenance are the main treatments to prevent recurrence and progression after initial TURBT; additional therapies are needed for those who do not respond to BCG. For localized MIBC, optimizing care and reducing morbidity following cystectomy are important goals. In metastatic disease, advances in our genetic understanding of bladder cancer and in immunotherapy are being translated into new therapies.

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

    PubMed

    Ward, Douglas G; Baxter, Laura; Gordon, Naheema S; Ott, Sascha; Savage, Richard S; Beggs, Andrew D; James, Jonathan D; Lickiss, Jennifer; Green, Shaun; Wallis, Yvonne; Wei, Wenbin; James, Nicholas D; Zeegers, Maurice P; Cheng, K K; Mathews, Glenn M; Patel, Prashant; Griffiths, Michael; Bryan, Richard T

    2016-01-01

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

  11. Bladder Cancer Advocacy Network

    MedlinePlus

    ... Grants Bladder Cancer Think Tank Bladder Cancer Research Network Bladder Cancer Genomics Consortium Get Involved Ways to ... RESEARCHERS Research Grants Bladder Cancer Think Tank Research Network Explore all research programs View all stories NEWSLETTER ...

  12. Nuclear matrix protein 22 for bladder cancer detection: comparative analysis of the BladderChek® and ELISA.

    PubMed

    Hatzichristodoulou, Georgios; Kübler, Hubert; Schwaibold, Hartwig; Wagenpfeil, Stefan; Eibauer, Cornelia; Hofer, Christian; Gschwend, Jürgen; Treiber, Uwe

    2012-11-01

    To compare nuclear matrix protein 22 expression by BladderChek® and ELISA, as urine-based assays for bladder cancer (BC) detection. Urine samples of 100 BC patients and 100 controls were analyzed. Comparative statistical evaluations were based on sensitivity and specificity. Seventy-one patients had primary and 29 recurrent BC. The sensitivity of BladderChek® was significantly higher compared to ELISA in the overall cancer cohort and in patients with primary BC (p<0.0001 and p=0.0001, respectively). Both tests demonstrated significant correlation of sensitivities and tumor stage/grade for the overall cancer cohort and for patients with primary BC. Both tests had specificity values of 100% in healthy individuals. Specificity was 93% for BladderChek® and 99% for ELISA in patients with benign diseases (p=0.048). BladderChek® may be clinically more useful for BC detection. Due to high specificity, BladderChek® could be used for high-risk screening. However, due to its low sensitivity, BladderChek® cannot replace but only complement cystoscopy for BC detection.

  13. Emerging Endoscopic Imaging Technologies for Bladder Cancer Detection

    PubMed Central

    Lopez, Aristeo; Liao, Joseph C.

    2014-01-01

    Modern urologic endoscopy is the result of continuous innovations since early 19th century. White light cystoscopy is the primary strategy for identification, resection, and local staging of bladder cancer. While highly effective, white light cystoscopy has several well-recognized shortcomings. Recent advances in optical imaging technologies and device miniaturization hold the potential to improve bladder cancer diagnosis and resection. Photodynamic diagnosis and narrow band imaging are the first to enter the clinical arena. Confocal laser endomicroscopy, optical coherence tomography, Raman spectroscopy, UV autofluorescence, and others have shown promising clinical and pre-clinical feasibility. We review their mechanisms of action, highlight their respective advantages, and propose future directions. PMID:24658832

  14. Transvaginal Sonography Versus Cystoscopy for Detecting Urinary Bladder Invasion in Early Stage Cervical Cancer

    PubMed Central

    Zutshi, Vijay; Garg, Anju; Batra, Swaraj

    2017-01-01

    Introduction Cervical cancer is a major cause of mortality from cancer among women. In it’s early stage pre operative staging with cystoscopy is a standard procedure for the detection of urinary bladder involvement. Aim The present study was conducted with the aim to compare the efficacy of Transvaginal Sonography (TVS) and cystoscopy in diagnosing bladder involvement in early stage cervical cancer patients by confirming it intraoperatively and further by histopathologic examination. Materials and Methods A prospective partially blinded study was conducted between March 2006 and September 2008 on 30 patients with early stage cervical cancer (Stage I and IIa) who were planned to undergo radical hysterectomy. Pre operatively, these patients underwent both TVS and cystoscopy to diagnose bladder involvement. Presence or absence of bladder involvement was then confirmed intra operatively and by histopathologic examination. Results In all the 30 patients studied, no bladder involvement was seen on cystoscopy where as TVS showed bladder involvement in three patients. Involvement of the bladder in these three patients was confirmed intra operatively and by histopathologic examination. Thus, in our study, TVS was 100% sensitive in detecting bladder involvement. Conclusion TVS is highly sensitive in diagnosing bladder involvement in early stage cervical cancer and could potentially detect cases missed with a cystoscopy.

  15. Detection of bladder cancer using novel DNA methylation biomarkers in urine sediments

    PubMed Central

    Chung, Woonbok; Bondaruk, Jolanta; Jelinek, Jaroslav; Lotan, Yair; Liang, Shoudan; Czerniak, Bogdan; Issa, Jean-Pierre J.

    2011-01-01

    Background Bladder cancer remains a lethal malignancy that can be cured if detected early. DNA hypermethylation is a common epigenetic abnormality in cancer that may serve as a marker of disease activity. Methods We selected 10 novel candidate genes from the most frequently hypermethylated genes detected by DNA microarray and bisulfite pyrosequencing of bladder cancers and applied them to detect bladder cancer in urine sediments. We analyzed DNA methylation in the candidate genes by quantitative methylation specific real time PCR (qMSP) to detect bladder cancer in urine sediments from 128 bladder cancer patients and 110 age-matched control subjects. Results Based on a multi-gene predictive model, we discovered 6 methylation markers (MYO3A, CA10, SOX11, NKX6-2, PENK and DBC1) as most promising for detecting bladder cancer. A panel of 4 genes (MYO3A, CA10, NKX6-2 and DBC1 or SOX11) had 81 % sensitivity and 97 % specificity, while a panel of 5 genes (MYO3A, CA10, NKX6-2, DBC1 and SOX11 or PENK) had 85 % sensitivity and 95 % specificity for detection of bladder cancer (AUC=0.939). Analyzing the data by cancer invasiveness, detection rate was 47 out of 58 (81 %) in non-muscle invasive tumors (pTa, Tis and pT1) and 62 out of 70 (90 %) in muscle invasive tumors (T2, T3 and T4). Conclusion This biomarker panel analyzed by qMSP may help the early detection of bladder tumors in urine sediments with high accuracy. Impact The panel of biomarker deserves validation in a large well-controlled prospectively collected sample set. PMID:21586619

  16. Bladder Cancer

    MedlinePlus

    ... schistosomiasis) is a common cause of bladder infections. Adenocarcinoma. Adenocarcinoma begins in cells that make up mucus-secreting glands in the bladder. Adenocarcinoma of the bladder is rare in the United ...

  17. Specific survivin dual fluorescence resonance energy transfer molecular beacons for detection of human bladder cancer cells

    PubMed Central

    Wang, Zhi-qiang; Zhao, Jun; Zeng, Jin; Wu, Kai-jie; Chen, Yu-le; Wang, Xin-yang; Chang, Luke S; He, Da-lin

    2011-01-01

    Aim: Survivin molecular beacons can be used to detect bladder cancer cells in urine samples non-invasively. The aim of this study is to improve the specificity of detection of bladder cancer cells using survivin dual fluorescence resonance energy transfer molecular beacons (FRET MBs) that have fluorophores forming one donor-acceptor pair. Methods: Survivin-targeting dual fluorescence resonance energy transfer molecular beacons with unique target sequences were designed, which had no overlap with the other genes in the apoptosis inhibitor protein family. Human bladder cancer cell lines 5637, 253J and T24, as well as the exfoliated cells in the urine of healthy adults and patients with bladder cancer were examined. Images of cells were taken using a laser scanning confocal fluorescence microscope. For assays using dual FRET MBs, the excitation wavelength was 488 nm, and the emission detection wavelengths were 520±20 nm and 560±20 nm, respectively. Results: The human bladder cancer cell lines and exfoliated cells in the urine of patients with bladder cancer incubated with the survivin dual FRET MBs exhibited strong fluorescence signals. In contrast, no fluorescence was detected in the survivin-negative human dermal fibroblasts-adult (HDF-a) cells or exfoliated cells in the urine of healthy adults incubated with the survivin dual FRET MBs. Conclusion: The results suggest that the survivin dual FRET MBs may be used as a specific and non-invasive method for early detection and follow-up of patients with bladder cancer. PMID:22019956

  18. UBC(®) Rapid Test for detection of carcinoma in situ for bladder cancer.

    PubMed

    Ecke, Thorsten H; Weiß, Sarah; Stephan, Carsten; Hallmann, Steffen; Barski, Dimitri; Otto, Thomas; Gerullis, Holger

    2017-05-01

    UBC(®) Rapid Test is a test that detects fragments of cytokeratins 8 and 18 in urine. We present results of a multicentre study measuring UBC(®) Rapid Test in bladder cancer patients and healthy controls with focus on carcinoma in situ (CIS) and high-grade bladder cancer. From our study with N = 452 patients, we made a stratified sub-analysis for carcinoma in situ of the urinary bladder. Clinical urine samples were used from 87 patients with tumours of the urinary bladder (23 carcinoma in situ, 23 non-muscle-invasive low-grade tumours, 21 non-muscle-invasive high-grade tumours and 20 muscle-invasive high-grade tumours) and from 22 healthy controls. The cut-off value was defined at 10.0 µg/L. Urine samples were analysed by the UBC(®) Rapid Test point-of-care system (concile Omega 100 POC reader). Pathological levels of UBC Rapid Test in urine are higher in patients with bladder cancer in comparison to the control group (p < 0.001). Sensitivity was calculated at 86.9% for carcinoma in situ, 30.4% for non-muscle-invasive low-grade bladder cancer, 71.4% for nonmuscle-invasive high grade bladder cancer and 60% for muscle-invasive high-grade bladder cancer, and specificity was 90.9%. The area under the curve of the quantitative UBC(®) Rapid Test using the optimal threshold obtained by receiveroperated curve analysis was 0.75. Pathological values of UBC(®) Rapid Test in urine are higher in patients with high-grade bladder cancer in comparison to low-grade tumours and the healthy control group. UBC(®) Rapid Test has potential to be more sensitive and specific urinary protein biomarker for accurate detection of high-grade patients and could be added especially in the diagnostics for carcinoma in situ and non-muscle-invasive high-grade tumours of urinary bladder cancer.

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

    PubMed Central

    Negraes, Priscilla D; Favaro, Francine P; Camargo, João Lauro V; Oliveira, Maria Luiza CS; Goldberg, José; Rainho, Cláudia A; Salvadori, Daisy MF

    2008-01-01

    Background Epigenetic alterations are a hallmark of human cancer. In this study, we aimed to investigate whether aberrant DNA methylation of cancer-associated genes is related to urinary bladder cancer recurrence. Methods A set of 4 genes, including CDH1 (E-cadherin), SFN (stratifin), RARB (retinoic acid receptor, beta) and RASSF1A (Ras association (RalGDS/AF-6) domain family 1), had their methylation patterns evaluated by MSP (Methylation-Specific Polymerase Chain Reaction) analysis in 49 fresh urinary bladder carcinoma tissues (including 14 cases paired with adjacent normal bladder epithelium, 3 squamous cell carcinomas and 2 adenocarcinomas) and 24 cell sediment samples from bladder washings of patients classified as cancer-free by cytological analysis (control group). A third set of samples included 39 archived tumor fragments and 23 matched washouts from 20 urinary bladder cancer patients in post-surgical monitoring. After genomic DNA isolation and sodium bisulfite modification, methylation patterns were determined and correlated with standard clinic-histopathological parameters. Results CDH1 and SFN genes were methylated at high frequencies in bladder cancer as well as in paired normal adjacent tissue and exfoliated cells from cancer-free patients. Although no statistically significant differences were found between RARB and RASSF1A methylation and the clinical and histopathological parameters in bladder cancer, a sensitivity of 95% and a specificity of 71% were observed for RARB methylation (Fisher's Exact test (p < 0.0001; OR = 48.89) and, 58% and 17% (p < 0.05; OR = 0.29) for RASSF1A gene, respectively, in relation to the control group. Conclusion Indistinct DNA hypermethylation of CDH1 and SFN genes between tumoral and normal urinary bladder samples suggests that these epigenetic features are not suitable biomarkers for urinary bladder cancer. However, RARB and RASSF1A gene methylation appears to be an initial event in urinary bladder carcinogenesis and

  20. Can CT Virtual Cystoscopy Replace Conventional Cystoscopy in Early Detection of Bladder Cancer?

    PubMed Central

    Abrol, Sachin; Jairath, Ankush; Ganpule, Sanika; Ganpule, Arvind; Mishra, Shashikant; Sabnis, Ravindra; Desai, Mahesh

    2015-01-01

    Aim. To correlate findings of conventional cystoscopy with CT virtual cystoscopy (CTVC) in detecting bladder tumors and to evaluate accuracy of virtual cystoscopy in early detection of bladder cancer. Material and Method. From June 2013 to June 2014, 50 patients (46 males, four females) with history and investigations suggestive of urothelial cancer, with mean age 62.76 ± 10.45 years, underwent CTVC by a radiologist as per protocol and subsequently underwent conventional cystoscopy (CPE) the same day or the next day. One urologist and one radiologist, blinded to the findings of conventional cystoscopy, independently interpreted the images, and any discrepant readings were resolved with consensus. Result. CTVC detected 23 out of 25 patients with bladder tumor(s) correctly. Two patients were falsely detected as negative while two were falsely labeled as positive in CTVC. Virtual and conventional cystoscopy were comparable in detection of tumor growth in urinary bladder. The sensitivity, specificity, positive predictive value, and negative predictive value of virtual cystoscopy were 92% each. Conclusion. CTVC correlates closely with the findings of conventional cystoscopy. Bladder should be adequately distended and devoid of urine at the time of procedure. However, more studies are required to define the role of virtual cystoscopy in routine clinical practice. PMID:26600802

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

    PubMed Central

    Smolensky, Dmitriy; Rathore, Kusum; Cekanova, Maria

    2016-01-01

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

  2. Technologic developments in the field of photonics for the detection of urinary bladder cancer.

    PubMed

    Palmer, Scott; Sokolovski, Sergei G; Rafailov, Edik; Nabi, Ghulam

    2013-12-01

    Bladder cancer is a common cause of morbidity and mortality worldwide in an aging population. Each year, thousands of people, mostly men, are diagnosed with this disease, but many of them present too late to receive optimal treatment. As with all cancers, early diagnosis of bladder cancer significantly improves the efficacy of therapy and increases survival and recurrence-free survival rates. Ongoing research has identified many limitations about the sensitivity of standard diagnostic procedures in detecting early-stage tumors and precancerous changes. The consequences of this are often tumor progression and increased tumor burden, leading to a decrease in patient quality of life and a vast increase in treatment costs. The necessity for improved early detection of bladder cancer has spurred on research into novel methods that use a wide range of biological and photonic phenomena. This review will broadly discuss standard detection methodologies and their major limitations before covering novel photonic techniques for early tumor detection and staging, assessing their diagnostic accuracy for flat and precancerous changes. We will do so in the context of both cystoscopic examination and the screening of voided urine and will also touch on the concept of using photonic technology as a surgical tool for tumor ablation.

  3. Update on novel imaging techniques for the detection of lymph node metastases in bladder cancer.

    PubMed

    Salminen, Antti P; Jambor, Ivan; Syvanen, Kari T; Bostrom, Peter J

    2016-04-01

    Staging of muscle-invasive bladder cancer (MIBC) remains a challenge. It is generally acknowledged that the most commonly used imaging techniques have a trend to either upstage or downstage the disease. The aim of this review article is to evaluate the currently available scientific evidence for the use of imaging modalities in preoperative bladder cancer staging with special attention to the detection of lymph node metastasis (LNM). A non-systematic literature search utilizing PubMed database with terms MIBC and LN and MRI or PET or CT was performed with the search limited to articles published between 2010 and 2015. Magnetic resonance imaging (MRI) has shown potential for local tumor detection and staging in multiple studies, but the accuracy for LNM detection remains disappointingly low. The LN staging accuracy is improved with the use of ultra-small super-paramagnetic particles of iron oxide (USPIO). This experimental method, however, is not commercially available at the moment. Positron emission tomography (PET), a functional imaging technique most commonly accompanied with computed tomography (PET-CT), may also have a role in the detection of bladder cancer LNM in the future. According to the currently available scientific evidence, the following could be recommended for MIBC staging: 1. use of pelvic MRI for primary tumor evaluation and local LNM detection acknowledging limited nodal imaging accuracy; 2. pelvic/abdominal/chest CT for evaluation of distant metastasis. The scientific evidence does not support the routine use of PET-CT (18F-FDG, 18F/11C-choline, 11C-acetate) in bladder cancer staging or in LNM detection.

  4. [Radiotherapy of bladder cancer].

    PubMed

    Riou, O; Chauvet, B; Lagrange, J-L; Martin, P; Llacer Moscardo, C; Charissoux, M; Lauche, O; Aillères, N; Fenoglietto, P; Azria, D

    2016-09-01

    Surgery (radical cystectomy) is the standard treatment of muscle-invasive bladder cancer. Radiochemotherapy has risen as an alternative treatment option to surgery as part as organ-sparing combined modality treatment or for patients unfit for surgery. Radiochemotherapy achieves 5-year bladder intact survival of 40 to 65% and 5-year overall survival of 40 to 50% with excellent quality of life. This article introduces the French recommendations for radiotherapy of bladder cancer: indications, exams, technique, dosimetry, delivery and image guidance.

  5. Bladder cancer.

    PubMed

    Ozen, H

    1996-05-01

    For many years it has been apparent that transitional cell carcinomas are a heterogeneous group of neoplasms with two clinical forms that exhibit distinctly different prognoses. Approximately 20% of the tumors are invasive at presentation, which is associated with poor prognoses. The remaining carcinomas are superficial, and an excellent outcome can be expected in the majority of patients treated with local therapies. However, 20% of the latter will progress to muscle invasive disease during the follow-up. The problem is to identify those who will progress and to distinguish those tumors likely to respond to therapy. Genetic changes that identify the subgroups of these tumors may be the key issue. During the past decade, studies of human cancer have begun to yield molecular information on the identity of multiple genetic changes that underline development and progression. Attention was focused initially on oncogenes and more recently on tumor-suppressor genes.

  6. Molecular pathology and biomarkers of bladder cancer.

    PubMed

    Czerniak, Bogdan

    2010-01-01

    Bladder cancer originates in the epithelial lining of the bladder's mucosa and develops in association with several habitual, industrial, and environmental risk factors via papillary and non-papillary pathways. In this chapter we review novel concepts concerning the molecular mechanisms of early field change in bladder neoplasia stemming from whole-organ genomic mapping studies. These mechanisms are discussed in the context of molecular pathogenesis of bladder cancer and in relation to treatment and biomarker-based detection strategies.

  7. Origins of Bladder Cancer.

    PubMed

    Czerniak, Bogdan; Dinney, Colin; McConkey, David

    2016-05-23

    Bladder cancer, one of the most frequently occurring human cancers, develops via two tracks referred to as papillary and nonpapillary that correspond to clinically different forms of the disease. Most bladder cancers are chemically induced, with tobacco smoking being the leading risk factor. Recent advances in bladder cancer research have enhanced our understanding of the origin of this disease from urothelial progenitor cells via field effects along papillary/luminal and nonpapillary/basal pathways. Evident from the outset of the disease, the diversity of the luminal and basal pathways, together with cell lineage tracing studies, postulates the origin of molecularly distinct subtypes from different uroprogenitor cells. The molecular mechanisms initiating field effects involve a new class of genes referred to as forerunner (FR) genes that generally map around major tumor suppressors such as RB1. These genes are silenced, predominantly by hypermethylation and less frequently by mutations, and drive the expansion of intraurothelial preneoplastic cells. Different FR genes are involved in various molecular subtypes of bladder cancer and they sensitize the uroprogenitor cells to the development of luminal and basal bladder cancers in animal models. In human bladder cancer, luminal and basal forms have dissimilar clinical behavior and response to conventional and targeted chemotherapeutic manipulations. These new research developments hold the promise of expanding our armamentarium of diagnostic and treatment options for patients with bladder cancer and improving our ability to select patients most likely to respond to a specific therapy.

  8. Lab on a chip for multiplexed immunoassays to detect bladder cancer using multifunctional dielectrophoretic manipulations.

    PubMed

    Chuang, Cheng-Hsin; Wu, Ting-Feng; Chen, Cheng-Ho; Chang, Kai-Chieh; Ju, Jing-Wei; Huang, Yao-Wei; Van Nhan, Vo

    2015-07-21

    A multiplexed immunosensor has been developed for the detection of specific biomarkers Galectin-1 (Gal-1) and Lactate Dehydrogenase B (LDH-B) present in different grades of bladder cancer cell lysates. In order to immobilize nanoprobes with different antibodies on a single chip we employed three-step programmable dielectrophoretic manipulations for focusing, guiding and trapping to enhance the fluorescent response and reduce the interference between the two antibody arrays. The chip consisted of a patterned indium tin oxide (ITO) electrode for sensing and a middle fish bone shaped gold electrode for focusing and guiding. Using ITO electrodes for the sensing area can effectively eliminate the background noise of fluorescence response as compared to metal electrodes. It was also observed that the three step manipulation increased fluorescence response after immunosensing by about 4.6 times as compared to utilizing DEP for just trapping the nanoprobes. Two different-grade bladder cancer cell lysates (grade I: RT4 and grade III: T24) were individually analyzed for detecting the protein expression levels of Gal-1 and LDH-B. The fluorescence intensity observed for Gal-1 is higher than that of LDH-B in the T24 cell lysate; however the response observed in RT4 is higher for LDH-B as compared to Gal-1. Thus we can effectively identify the different grades of bladder cancer cells. In addition, the platform for DEP manipulation developed in this study can enable real time detection of multiple analytes on a single chip and provide more practical benefits for clinical diagnosis.

  9. Diagnostic approach for cancer cells in urine sediments by 5-aminolevulinic acid-based photodynamic detection in bladder cancer.

    PubMed

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

    2014-05-01

    Bladder urothelial carcinoma is diagnosed and followed up after transurethral resection using a combination of cystoscopy, urine cytology and urine biomarkers at regular intervals. However, cystoscopy can overlook flat lesions like carcinoma in situ, and the sensitivity of urinary tests is poor in low-grade tumors. There is an emergent need for an objective and easy urinary diagnostic test for the management of bladder cancer. In this study, three different modalities for 5-aminolevulinic acid (ALA)-based photodynamic diagnostic tests were used. We developed a compact-size, desktop-type device quantifying red fluorescence in cell suspensions, named "Cellular Fluorescence Analysis Unit" (CFAU). Urine samples from 58 patients with bladder cancer were centrifuged, and urine sediments were then treated with ALA. ALA-treated sediments were subjected to three fluorescence detection assays, including the CFAU assay. The overall sensitivities of conventional cytology, BTA, NMP22, fluorescence cytology, fluorescent spectrophotometric assay and CFAU assay were 48%, 33%, 40%, 86%, 86% and 87%, respectively. Three different ALA-based assays showed high sensitivity and specificity. The ALA-based assay detected low-grade and low-stage bladder urothelial cells at shigher rate (68-80% sensitivity) than conventional urine cytology, BTA and NMP22 (8-20% sensitivity). Our findings demonstrate that the ALA-based fluorescence detection assay is promising tool for the management of bladder cancer. Development of a rapid and automated device for ALA-based photodynamic assay is necessary to avoid the variability induced by troublesome steps and low stability of specimens.

  10. What Is Bladder Cancer?

    MedlinePlus

    ... bladder, which is called the urothelium or transitional epithelium . As the cancer grows into or through the ... in the inner layer of cells (the transitional epithelium) but have not grown into the deeper layers. ...

  11. Bladder cancer detection using a peptide substrate of the 20S proteasome.

    PubMed

    Gruba, Natalia; Wysocka, Magdalena; Brzezińska, Magdalena; Dębowski, Dawid; Sieńczyk, Marcin; Gorodkiewicz, Ewa; Guszcz, Tomasz; Czaplewski, Cezary; Rolka, Krzysztof; Lesner, Adam

    2016-08-01

    The 20S catalytic core of the human 26S proteasome can be secreted from cells, and high levels of extracellular 20S proteasome have been linked to many types of cancers and autoimmune diseases. Several diagnostic approaches have been developed that detect 20S proteasome activity in plasma, but these suffer from problems with efficiency and sensitivity. In this report, we describe the optimization and synthesis of an internally quenched fluorescent substrate of the 20S proteasome, and investigate its use as a potential diagnostic test in bladder cancer. This peptide, 2-aminobenzoic acid (ABZ)-Val-Val-Ser-Tyr-Ala-Met-Gly-Tyr(3-NO2 )-NH2 , is cleaved by the chymotrypsin 20S proteasome subunit and displays an excellent specificity constant value (9.7 × 10(5)  m(-1) ·s(-1) ) and a high kcat (8 s(-1) ). Using this peptide, we identified chymotrypsin-like proteasome activity in the majority of urine samples obtained from patients with bladder cancer, whereas the proteasome activity in urine samples from healthy volunteers was below the detection limit (0.5 pm). These findings were confirmed by an inhibitory study and immunochemistry methods. © 2016 Federation of European Biochemical Societies.

  12. Urinary markers for bladder cancer

    PubMed Central

    Smith, Zachary L.

    2013-01-01

    Bladder cancer has the fifth highest incidence of all malignancies in the United States, with a propensity to recur, requiring lifelong surveillance after diagnosis. Urinary markers of disease have been of extreme interest in this field in an effort to simplify surveillance schedules and improve early detection of tumors. Many markers have been described, but most remain investigational. However, some markers have undergone clinical trials and are approved for clinical use. In this review, urinary markers and their application for screening and surveillance of bladder cancer are discussed. PMID:23864929

  13. Circulating Biomarkers in Bladder Cancer

    PubMed Central

    Nandagopal, Lakshminarayanan; Sonpavde, Guru

    2016-01-01

    Bladder cancer is a molecularly heterogeneous disease characterized by multiple unmet needs in the realm of diagnosis, clinical staging, monitoring and therapy. There is an urgent need to develop precision medicine for advanced urothelial carcinoma. Given the difficulty of serial analyses of metastatic tumor tissue to identify resistance and new therapeutic targets, development of non-invasive monitoring using circulating molecular biomarkers is critically important. Although the development of circulating biomarkers for the management of bladder cancer is in its infancy and may currently suffer from lower sensitivity of detection, they have inherent advantages owing to non-invasiveness. Additionally, circulating molecular alterations may capture tumor heterogeneity without the sampling bias of tissue biopsy. This review describes the accumulating data to support further development of circulating biomarkers including circulating tumor cells, cell-free circulating tumor (ct)-DNA, RNA, micro-RNA and proteomics to improve the management of bladder cancer. PMID:28035318

  14. Aurora Kinase A is a Biomarker for Bladder Cancer Detection and Contributes to its Aggressive Behavior.

    PubMed

    Mobley, Aaron; Zhang, Shizhen; Bondaruk, Jolanta; Wang, Yan; Majewski, Tadeusz; Caraway, Nancy P; Huang, Li; Shoshan, Einav; Velazquez-Torres, Guermarie; Nitti, Giovanni; Lee, Sangkyou; Lee, June Goo; Fuentes-Mattei, Enrique; Willis, Daniel; Zhang, Li; Guo, Charles C; Yao, Hui; Baggerly, Keith; Lotan, Yair; Lerner, Seth P; Dinney, Colin; McConkey, David; Bar-Eli, Menashe; Czerniak, Bogdan

    2017-01-19

    The effects of AURKA overexpression associated with poor clinical outcomes have been attributed to increased cell cycle progression and the development of genomic instability with aneuploidy. We used RNA interference to examine the effects of AURKA overexpression in human bladder cancer cells. Knockdown had minimal effects on cell proliferation but blocked tumor cell invasion. Whole genome mRNA expression profiling identified nicotinamide N-methyltransferase (NNMT) as a downstream target that was repressed by AURKA. Chromatin immunoprecipitation and NNMT promoter luciferase assays revealed that AURKA's effects on NNMT were caused by PAX3-mediated transcriptional repression and overexpression of NNMT blocked tumor cell invasion in vitro. Overexpression of AURKA and activation of its downstream pathway was enriched in the basal subtype in primary human tumors and was associated with poor clinical outcomes. We also show that the FISH test for the AURKA gene copy number in urine yielded a specificity of 79.7% (95% confidence interval [CI] = 74.2% to 84.1%), and a sensitivity of 79.6% (95% CI = 74.2% to 84.1%) with an AUC of 0.901 (95% CI = 0.872 to 0.928; P < 0.001). These results implicate AURKA as an effective biomarker for bladder cancer detection as well as therapeutic target especially for its basal type.

  15. Aurora Kinase A is a Biomarker for Bladder Cancer Detection and Contributes to its Aggressive Behavior

    PubMed Central

    Mobley, Aaron; Zhang, Shizhen; Bondaruk, Jolanta; Wang, Yan; Majewski, Tadeusz; Caraway, Nancy P.; Huang, Li; Shoshan, Einav; Velazquez-Torres, Guermarie; Nitti, Giovanni; Lee, Sangkyou; Lee, June Goo; Fuentes-Mattei, Enrique; Willis, Daniel; Zhang, Li; Guo, Charles C.; Yao, Hui; Baggerly, Keith; Lotan, Yair; Lerner, Seth P.; Dinney, Colin; McConkey, David; Bar-Eli, Menashe; Czerniak, Bogdan

    2017-01-01

    The effects of AURKA overexpression associated with poor clinical outcomes have been attributed to increased cell cycle progression and the development of genomic instability with aneuploidy. We used RNA interference to examine the effects of AURKA overexpression in human bladder cancer cells. Knockdown had minimal effects on cell proliferation but blocked tumor cell invasion. Whole genome mRNA expression profiling identified nicotinamide N-methyltransferase (NNMT) as a downstream target that was repressed by AURKA. Chromatin immunoprecipitation and NNMT promoter luciferase assays revealed that AURKA’s effects on NNMT were caused by PAX3-mediated transcriptional repression and overexpression of NNMT blocked tumor cell invasion in vitro. Overexpression of AURKA and activation of its downstream pathway was enriched in the basal subtype in primary human tumors and was associated with poor clinical outcomes. We also show that the FISH test for the AURKA gene copy number in urine yielded a specificity of 79.7% (95% confidence interval [CI] = 74.2% to 84.1%), and a sensitivity of 79.6% (95% CI = 74.2% to 84.1%) with an AUC of 0.901 (95% CI = 0.872 to 0.928; P < 0.001). These results implicate AURKA as an effective biomarker for bladder cancer detection as well as therapeutic target especially for its basal type. PMID:28102366

  16. CCL18 in a multiplex urine-based assay for the detection of bladder cancer.

    PubMed

    Urquidi, Virginia; Kim, Jeongsoon; Chang, Myron; Dai, Yunfeng; Rosser, Charles J; Goodison, Steve

    2012-01-01

    The early detection of bladder cancer (BCa) is pivotal for successful patient treatment and management. Through genomic and proteomic studies, we have identified a number of bladder cancer-associated biomarkers that have potential clinical utility. In a case-control study, we examined voided urines from 127 subjects: 64 tumor-bearing subjects and 63 controls. The urine concentrations of the following proteins were assessed by enzyme-linked immunosorbent assay (ELISA); C-C motif chemokine 18 (CCL18), Plasminogen Activator Inhibitor 1 (PAI-1) and CD44. Data were compared to a commercial ELISA-based BCa detection assay (BTA-Trak©) and voided urinary cytology. We used analysis of the area under the curve of receiver operating characteristic curves to compare the ability of CCL18, PAI-1, CD44, and BTA to detect BCa in voided urine samples. Urinary concentrations of CCL18, PAI-1, and BTA were significantly elevated in subjects with BCa. CCL18 was the most accurate biomarker (AUC; 0.919; 95% confidence interval [CI], 0.8704-0.9674). Multivariate regression analysis highlighted CCL18 (OR; 18.31; 95% CI, 4.95-67.70, p<0.0001) and BTA (OR; 6.43; 95% CI, 1.86-22.21, p = 0.0033) as independent predictors of BCa in voided urine samples. The combination of CCL18, PAI-1 and CD44 improved the area under the curve to 0.938. Preliminary results indicate that CCL18 was a highly accurate biomarker for BCa detection in this cohort. Monitoring CCL18 in voided urine samples has the potential to improve non-invasive tests for BCa diagnosis. Furthermore using the combination of CCL18, PAI-1 and CD44 may make the model more robust to errors to detect BCa over the individual biomarkers or BTA.

  17. On the influence of the instillation time on the results of HAL (Hexvix) fluorescence detection of superficial bladder cancer

    NASA Astrophysics Data System (ADS)

    Jichlinski, Patrice; Aymon, Daniela; Wagnieres, Georges A.; Marti, Alexandre; Lange, Norbert; Guillou, Louis; Leisinger, Hans-Juerg; van den Bergh, Hubert

    2003-10-01

    Hexyl aminolevulinate (HAL) fluorescence cystoscopy is being investigated as a new diagnostic tool for the detection of flat urothelial malignancies in bladder cancers. However, the influence of the bladder instillation time on the performance of this detection modality has not been addressed up to now. We report our initial experience comparing different instillation schedules of HAL cystoscopy in the diagnosis of superficial bladder cancer. A total of 718 fluorescent positive (433) and fluorescence negative (285) biopsies have been taken in the bladder of 143 patients using the Storz D-light fluorescence imaging system (Karl Storz, Tuttlingen, Germany) which allows both white and blue light (380-450 nm) bladder wall inspection. Following hospitalisation, 50 ml of HAL (8mM) phosphate buffer solution was instilled into the bladder of patients during one hour (1 hour protocol involving 57 patients), or during two hours followed by a two hours resting time after removal of the solution (2+2 hours protocol involving 86 patients). Both instillation subgroups were homogeneous in terms of proportion of high risk disease, previous BCG treatment and/or recurrent disease. This study indicates that the instillation duration does not influence the results of HAL (Hexvix) fluorescence cystoscopy in our conditions. Compared to the standard use of ALA, HAL (Hexvix) fluorescence cystoscopy allows a significant reduction of the instillation time (to less than one hour) without prejudicing the efficacy of the method, what represents a real advantage in daily clinical practice.

  18. [Clinical evaluation of urinary basic fetoprotein and the BTA test for detection of bladder cancer].

    PubMed

    Imamura, M; Inoue, K; Megumi, Y; Nishimura, M; Ohmori, K; Nishimura, K

    2000-10-01

    We compared the results of urinary basic fetoprotein (BFP) and the BTA test with those of urinary cytology in patients with bladder cancer. We also analyzed the urinary BFP and the BTA test results in patients with benign diseases and postoperative bladder cancer with no evidence of recurrence. The cutoff value for urinary BFP was set at 10 ng/ml. Classes 4 and 5 according to urinary cytology were defined as positive. The sensitivity of urinary BFP for Ta, 1 bladder cancer was significantly higher than that of urinary cytology (p < 0.05). The urinary cytology positive rate for Ta, 1 bladder cancer improved when combined with urinary BFP and the BTA test. The urinary BFP positive rate for benign diseases was significantly higher in patients with pyuria than in patients without pyuria (p < 0.05). The BTA test positive rate for benign diseases was higher in patients with pyuria than in patients without pyuria. The urinary BFP and the BTA test positive rates for postoperative bladder cancer with no evidence of recurrence was significantly higher in patients with urinary diversion than in patients without urinary diversion (BFP: p < 0.01, BTA: p < 0.05).

  19. The detection of genetic markers of bladder cancer in urine and serum.

    PubMed

    Lodde, Michele; Fradet, Yves

    2008-09-01

    To review the most recent publications focusing on the use of genetic markers (DNA, RNA and nucleosides) in urine and serum and provide an opinion on their potential utility for screening, diagnosis and prognosis of urothelial carcinoma. Several studies have shown the diagnostic utility of urine tests based on improved microsatellite analysis of loss-of-heterozygosity, detection of fibroblast growth factor receptor 3 mutations, detection of single RNA and multiple gene signatures as well as nucleoside profiles. Although of interest, all these studies lack appropriate controls and validation before being considered as serious candidate clinical biomarkers. The presence of fibroblast growth factor receptor 3 mutations in tumors was identified as a hallmark of tumors of low malignant potential. Serum DNA analysis of hypermethylation of a set of genes shows promise as an indicator of cancer progression and mortality. Finally, a case-control study of 775 patients and 397 controls showed that DNA hypomethylation of blood cells combined with smoking habits can provide stratification of cancer risk that may be very helpful in conceiving bladder cancer screening studies. The challenge is not so much to identify better markers or methods but rather to commit to implementing them into clinical practice by stimulating and funding the clinical trials required.

  20. Detection of low frequency FGFR3 mutations in the urine of bladder cancer patients using next-generation deep sequencing

    PubMed Central

    Millholland, John M; Li, Shuqiang; Fernandez, Cecilia A; Shuber, Anthony P

    2012-01-01

    Biological fluid-based noninvasive biomarker assays for monitoring and diagnosing disease are clinically powerful. A major technical hurdle for developing these assays is the requirement of high analytical sensitivity so that biomarkers present at very low levels can be consistently detected. In the case of biological fluid-based cancer diagnostic assays, sensitivities similar to those of tissue-based assays are difficult to achieve with DNA markers due to the high abundance of normal DNA background present in the sample. Here we describe a new urine-based assay that uses ultradeep sequencing technology to detect single mutant molecules of fibroblast growth factor receptor 3 (FGFR3) DNA that are indicative of bladder cancer. Detection of FGFR3 mutations in urine would provide clinicians with a noninvasive means of diagnosing early-stage bladder cancer. The single-molecule assay detects FGFR3 mutant DNA when present at as low as 0.02% of total urine DNA and results in 91% concordance with the frequency that FGFR3 mutations are detected in bladder cancer tumors, significantly improving diagnostic performance. To our knowledge, this is the first practical application of next-generation sequencing technology for noninvasive cancer diagnostics. PMID:24199178

  1. Virtual cystoscopy, computed tomography urography and optical cystoscopy for the detection and follow-up for bladder cancer.

    PubMed

    Ibáñez Muñoz, D; Quintana Martínez, I; Fernández Militino, A; Sánchez Zalabardo, D; Sarria Octavio de Toledo, L; Cozcolluela Cabrejas, R

    To evaluate the utility of virtual cystoscopy (VC) performed with CT urography in patients being studied under gross hematuria or patients being followed-up after a previous bladder cancer and compare the results with those obtained with gold standard technique (optical cystoscopy). Retrospective study of 117 patients who were referred for VC by the Urology Department between May 2014 and May 2015. Those patients presented with gross hematuria or they were previously treated patients from bladder cancer being followed up. These patients were evaluated with MDCT and virtual cystoscopy after distending the bladder with air. The results were compared with those obtained with optical cystoscopy which was performed no more than a week after. The global sensitivity and specificity of VC were 81,8 and 92,1%. Aditional findings detected in CT urography were an aortic dissection, urinary lithiasis and colonic metastasis. VC seems an useful technique in the diagnosis and follow-up for bladder cancer with a good correlation with OC. The main limitations are the impossibility of biopsy during the procedure and the detection of erythematous lesions. Collateral findings can be detected performed with CT urography although the high radiation exposure does not recommend their combined use. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. A multi-analyte assay for the non-invasive detection of bladder cancer.

    PubMed

    Goodison, Steve; Chang, Myron; Dai, Yunfeng; Urquidi, Virginia; Rosser, Charles J

    2012-01-01

    Accurate urinary assays for bladder cancer (BCa) detection would benefit both patients and healthcare systems. Through genomic and proteomic profiling of urine components, we have previously identified a panel of biomarkers that can outperform current urine-based biomarkers for the non-invasive detection of BCa. Herein, we report the diagnostic utility of various multivariate combinations of these biomarkers. We performed a case-controlled validation study in which voided urines from 127 patients (64 tumor bearing subjects) were analyzed. The urinary concentrations of 14 biomarkers (IL-8, MMP-9, MMP-10, SDC1, CCL18, PAI-1, CD44, VEGF, ANG, CA9, A1AT, OPN, PTX3, and APOE) were assessed by enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of each biomarker and multivariate models were compared using receiver operating characteristic curves and the chi-square test. An 8-biomarker model achieved the most accurate BCa diagnosis (sensitivity 92%, specificity 97%), but a combination of 3 of the 8 biomarkers (IL-8, VEGF, and APOE) was also highly accurate (sensitivity 90%, specificity 97%). For comparison, the commercial BTA-Trak ELISA test achieved a sensitivity of 79% and a specificity of 83%, and voided urine cytology detected only 33% of BCa cases in the same cohort. These data show that a multivariate urine-based assay can markedly improve the accuracy of non-invasive BCa detection. Further validation studies are under way to investigate the clinical utility of this panel of biomarkers for BCa diagnosis and disease monitoring.

  3. Immunological detection of human bladder carcinoma.

    PubMed Central

    Monaco, A P; Gozzo, J J; Schlesinger, R M; Codish, S D

    1975-01-01

    A rabbit antiserum (RABCa) to membrane antigenic extracts of human bladder carcinomas was produced. RABCa failed to detect bladder cancer-specific antigens in gel diffusion reaction against antigenic extracts of bladder carcinoma and normal bladder mucosa. However, RABCa showed higher complement fixation activity against urines from bladder cancer patients compared with normal urines. The micro-complement fixation (CF) assay (108 patients) was positive in 17 of 27 bladder cancer patients (62.9%) compared to only 1 of 29 normals (3.4%). However, 10 of 11 patients with urinary infections also were positive. A micro-Ouchterlony agar gel diffusion assay was also used to study urine samples (118 patients). RABCa produced separate precipitin bands against 20 of 30 bladder cancer urines (66.7%) while only 1 of 24 normal urines gave these bands (4.2%). Again, infected urines were positive (9 of 11). Additionally, urine from patients with benign urological disease was often positive in CF (11 of 41) and Ouchterlony (15 of 43) assays. RABCa serum was absorbed with normal bladder mucosa membrane extracts either once (1X) or three times (3X) to increase the specificity of the Ouchterlong gel diffusion assay. Using RABCa (1X) the per cent of positive bladder cancer urines and normals decreased only slightly, while the number of positive reactions against benign urological disease urines dramatically decreased (17.9%). RABCa (3X) further reduced the per cent of positive reactions with benign urological disease urines (10.3%), greatly reduced the reactivity with infected urines (60.0%), and gave no positive reactions with normal urines, without significantly decreasing the abiltiy to detect bladder carcinoma (51.9%). Although RABCa was 100% effective in detecting high grade (III) bladder tumors, almost two-thirds of all transitional cell papilloma urines were also positive. The nature of the material detected in bladder cancer and infected urines by RABCa is probably a product of

  4. Bubble-driven mixer integrated with a microfluidic bead-based ELISA for rapid bladder cancer biomarker detection.

    PubMed

    Lin, Yen-Heng; Wang, Chia-Chu; Lei, Kin Fong

    2014-04-01

    In this study, fine bubbles were successfully generated and used as a simple, low-cost driving force for mixing fluids in an integrated microfluidic bead-based enzyme-linked immunosorbent assay (ELISA) to rapidly and quantitatively detect apolipoprotein A1 (APOA1), a biomarker highly correlated with bladder cancer. A wooden gas diffuser was embedded underneath a microfluidic chip to refine injected air and generate bubbles of less than 0.3 mm. The rising bubbles caused disturbances and convection in the fluid, increasing the probability of analyte interaction. This setup not only simplifies the micromixer design but also achieves rapid mixing with a small airflow as a force. We used this bubble-driven micromixer in a bead-based ELISA that targeted APOA1. The results indicate that this micromixer reduced the time for each incubation from 60 min in the conventional assay to 8 min with the chip, resulting in a reduction of total ELISA reaction time from 3-4 h to 30-40 min. Furthermore, the concentration detection limit was 9.16 ng/mL, which was lower than the detection cut-off value (11.16 ng/mL) for bladder cancer diagnosis reported in the literature. Therefore, this chip can be used to achieve rapid low-cost bladder cancer detection and may be used in point-of-care cancer monitoring.

  5. Spectroscopic Imaging of Bladder Cancer

    SciTech Connect

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

    2003-01-01

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

  6. Bladder cancer biomarker array to detect aberrant levels of proteins in urine.

    PubMed

    Gogalic, S; Sauer, U; Doppler, S; Preininger, C

    2015-02-07

    Bladder cancer (BCa) is a serious malignancy of the urinary tract worldwide and also prominent for its high rate of recurrence incorporating 50% of all treated patients. To reduce relapse of BCa, lifelong surveillance of patients is essential leading to high treatment costs. The gold standard for the diagnosis of bladder cancer is cystoscopy. It is very sensitive, but due to high costs and its invasive nature this method for routine diagnosis of bladder cancer remains questionable. Because of this and the required surveillance of patients suffering from bladder cancer, urine based markers represent a new potential field of investigation. Literature at the National Center of Biological Information (NCBI) was retrieved for a potential marker panel offering specific protein signatures and used to develop a sensitive and accurate chip assay to monitor BCa. Discovery of possible bladder cancer protein markers is compiled by extensive literature search including 1077 recently (15.01.2008-20.03.2014) published research articles. Validation of this literature is done by selection based on prior defined inclusion and exclusion criteria. A set of six putative biomarkers (VEGF, IL-8, MMP-9, MMP-7, survivin and Cyfra 21.1) was identified and a non-invasive microarray developed to be used for further clinical validation. Investigation regarding optimized urine preparation and assay development, to enhance assay sensitivity for the marker panel, was carried out. This protein based BCa chip enables the fast (within 5 h), simultaneous, easy to operate, cheap, early and non-invasive determination of BCa and is ready for clinical evaluation.

  7. 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.

  8. [Diet in bladder cancer ethiopathogenesis].

    PubMed

    Radosavljević, V; Ilić, M; Janković, S; Djokić, M

    2005-01-01

    The aim of this paper is to show influence of different foods on bladder cancer appearance, as well as possible consequent ways of prevention. Consuption of food rich in animal fat and cholesterol, fried foods, especially several times used cookin oil for frying, processed meat with additives (nitrates, nitrites, azo-colourrs) can influence bladder cancer occurrence. Regularly, continous consumption of fermented milk products, which contains come types of milky--acids bacterias, is considered as protective factor in developing bladder cancer. Reports that fruit and vegetable are protective food items are pretty consistent. Data about mineral intake and bladder cancer are obscure.

  9. Narrow-band imaging flexible cystoscopy in the detection of recurrent urothelial cancer of the bladder.

    PubMed

    Bryan, Richard T; Billingham, Lucinda J; Wallace, D Michael A

    2008-03-01

    To investigate whether narrow-band imaging (NBI) flexible cystoscopy improves the detection rate of urothelial carcinomas (UCs) of the bladder. NBI is an optical image enhancement technology in which the narrow bandwidth of light is strongly absorbed by haemoglobin and penetrates only the surface of tissue, increasing the visibility of capillaries and other delicate tissue surface structures by enhancing contrast between the two. Between November 2005 and May 2007 at the Queen Elizabeth Hospital, Birmingham, NBI flexible cystoscopy was performed on 29 patients with known recurrences of UC of the bladder after initial conventional white-light imaging (WLI) flexible cystoscopy with the same instrument (Olympus Lucera sequential RGB endoscopy system). Subjectively, NBI provided a much clearer view of bladder UCs and in particular their delicate capillary architecture. Objectively, NBI detected 15 additional UCs in 12 of 29 patients (41%), as compared with WLI. The mean (sd) difference was 0.52 (0.74) UCs per patient (P < 0.001, Wilcoxon signed-rank test). Even in the few patients studied there is strong evidence that NBI differs from WLI in the number of UCs it detects, with a significantly increased detection rate. We feel that further evaluation of NBI flexible cystoscopy in more patients will show this technique to be highly valuable in the detection of both new and recurrent bladder UCs, and this work is continuing in our unit.

  10. Contemporary Management of Bladder Cancer

    PubMed Central

    Bell, David; Fradet, Yves

    1991-01-01

    Bladder cancer is currently the fifth most common cancer in Western society, and its incidence appears to be increasing. Important advances have recently occurred in both diagnostic and therapeutic approaches to bladder neoplasms. Presentation is not unique, and physician awareness is important to identify patients who are at risk for bladder neoplasia and consequently require further investigation. A diagnostic approach and contemporary management are discussed. ImagesFigure 1Figure 4 PMID:21229043

  11. Chemoprevention of bladder cancer.

    PubMed

    Kamat, Ashish M; Lamm, Donald L

    2002-02-01

    The data presented herein, although highly supportive for a protective role of various nutrients against bladder cancer, are far from definitive. Many authorities question the validity of current recommendations for nutritional chemoprevention against bladder cancer. The reason for the wide variations reported in epidemiologic studies lies in the nature of observational studies. Dietary studies are limited in their conclusions because the protection afforded by the consumption of a particular nutrient may be multifactorial, with different components of the food exerting potential chemopreventive effects. Furthermore, measuring levels of nutrients in the food intake of populations is confounded by factors that might affect these levels and also the incidence of cancer. For example, vitamin A can come from animal or vegetarian sources. Because animal fat has been identified as a potential carcinogen in man, depending on the source of the vitamin, varying levels of protection might be deduced. In addition, chemoprevention studies using dietary supplements are expected to have mild effects, and large studies would be required to confirm statistical significance. Even with agents such as intravesical chemotherapy, only half the studies achieve statistical significance [29]. Prospective randomized trials with a large sample size, longer follow-up, and an extended duration of treatment are needed to clarify the association between micronutrients and cancer protection. With these caveats in mind, several recommendations can be made. Simple measures, such as drinking more fluids (especially water), can have a profound impact on the incidence of bladder cancer. Vitamins are being extensively studied in chemopreventive trials for different cancers. There is strong evidence for a chemoprotective effect of vitamin A in bladder cancer. The authors recommend 32,000 IU/day of vitamin A initially, with lower doses (24,000 IU) for persons less than 50 kg. Because liver toxicity is a

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

    PubMed Central

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

    2015-01-01

    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. PMID:25628642

  13. Immunotherapy for bladder cancer

    PubMed Central

    Fuge, Oliver; Vasdev, Nikhil; Allchorne, Paula; Green, James SA

    2015-01-01

    It is nearly 40 years since Bacillus Calmette–Guérin (BCG) was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment. As a better understanding of its mechanism of action and the clinical response to it have evolved, some of the questions around optimal dosing and treatment protocols have been answered. However, its potential for toxicity and failure to produce the desired clinical effect in a significant cohort of patients presents an ongoing challenge to clinicians and researchers alike. This review summarizes the evidence behind the established mechanism of action of BCG in bladder cancer, highlighting the extensive array of immune molecules that have been implicated in its action. The clinical aspects of BCG are discussed, including its role in reducing recurrence and progression, the optimal treatment regime, toxicity and, in light of new evidence, whether or not there is a superior BCG strain. The problems of toxicity and non-responders to BCG have led to development of new techniques aimed at addressing these pitfalls. The progress made in the laboratory has led to the identification of novel targets for the development of new immunotherapies. This includes the potential augmentation of BCG with various immune factors through to techniques avoiding the use of BCG altogether; for example, using interferon-activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The potential role of gene, virus, or photodynamic therapy as an alternative to BCG is also reviewed. Recent interest in the immune check point system has led to the development of monoclonal antibodies against proteins involved in this pathway. Early findings suggest benefit in metastatic disease, although the role in superficial bladder cancer remains unclear. PMID:26000263

  14. 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.

  15. Endoscopic optical coherence tomography with a modified microelectromechanical systems mirror for detection of bladder cancers

    NASA Astrophysics Data System (ADS)

    Xie, Tuqiang; Xie, Huikai; Fedder, Gary K.; Pan, Yingtian

    2003-11-01

    Experimental results of a modified micromachined microelectromechanical systems (MEMS) mirror for substantial enhancement of the transverse laser scanning performance of endoscopic optical coherence tomography (EOCT) are presented. Image distortion due to buckling of MEMS mirror in our previous designs was analyzed and found to be attributed to excessive internal stress of the transverse bimorph meshes. The modified MEMS mirror completely eliminates bimorph stress and the resultant buckling effect, which increases the wobbling-free angular optical actuation to greater than 37°, exceeding the transverse laser scanning requirements for EOCT and confocal endoscopy. The new optical coherence tomography (OCT) endoscope allows for two-dimensional cross-sectional imaging that covers an area of 4.2 mm × 2.8 mm (limited by scope size) and at roughly 5 frames/s instead of the previous area size of 2.9 mm × 2.8 mm and is highly suitable for noninvasive and high-resolution imaging diagnosis of epithelial lesions in vivo. EOCT images of normal rat bladders and rat bladder cancers are compared with the same cross sections acquired with conventional bench-top OCT. The results clearly demonstrate the potential of EOCT for in vivo imaging diagnosis and precise guidance for excisional biopsy of early bladder cancers.

  16. 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.

  17. 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

  18. Significance of random bladder biopsies in superficial bladder cancer.

    PubMed

    May, F; Treiber, U; Hartung, R; Schwaibold, H

    2003-07-01

    We investigated to what extent biopsies of normal-appearing urothelium taken from patients with superficial bladder cancer (Ta, T1, Tis) showed malignant disease and whether those findings had impact on therapeutical decisions. 1033 consecutive patients presenting with Ta, T1 or Tis (carcinoma in situ) superficial bladder tumors at increased risk for recurrence underwent multiple random biopsies from normal-appearing urothelium during transurethral resection (TUR). Patients with small, primary, singular tumors (smaller or equal to 1cm) were excluded from random biopsies. No tumor was found in the random biopsies of 905 patients (87.6%). 128 patients (12.4%) showed urothelial bladder cancer in their random biopsies (Tis: 74, Ta: 41, T1: 12, T2: 1). In 14 patients, where transurethral resection of the primary tumor revealed no signs of malignancy, urothelial bladder cancer was detected in the random biopsy material: Ta 8 patients, Tis 5 patients and T1 one patient. 21 patients with Ta tumors and 29 patients with T1 disease showed concomitant Tis. Upstaging of the primary, resected tumor by histological examination of the random biopsy material occurred in 75 patients (7%). Altogether, due to the random biopsy results therapy was altered in 70 patients (6.8%) of our series: It changed intravesical chemotherapy to BCG in 45, provoked a second TUR in 48 and cystectomy in 15 patients. While the clinical significance of random biopsies is still controversial, random biopsy results had strong impact on therapeutical decisions in our series. Regarding random bladder biopsies a simple tool for the urologist to identify high risk groups of patients, we recommend them as part of the routine management of superficial bladder cancer.

  19. Evans blue-mediated white-light detection of non-muscle-invasive bladder cancer: A preclinical feasibility and safety study using a rat bladder urothelial cell carcinoma model

    PubMed Central

    Elsen, Sanne; Lerut, Evelyne; Van Der Aa, Frank; Van Cleynenbreugel, Ben; Van Poppel, Hendrik; De Witte, Peter

    2016-01-01

    Photodynamic diagnosis (PDD) improves the detection of non-muscle-invasive bladder cancer (NMIBC). However, white-light (WL) cystoscopy remains the technique routinely used in urological clinics. A more cost-effective but equally performant alternative to PDD may encompass the use of an intense tumoritropic dye in combination with WL cystoscopy. Using a preclinical setting, we investigated the practical aspects of the use of Evans blue (EB) dye for the possible future detection of NMIBC using WL cystoscopy. A solution of 1 and 5 mM EB was instilled into healthy and AY-27 tumor-bearing rat bladders. The bladders were then rapidly dissected and the inner walls were inspected for EB using WL stereomicroscopy. EB present in the bladders and the plasma was also quantified using high performance liquid chromatography. To assess the effects of repeated instillations on normal rat bladders, EB was instilled for 7 consecutive days, after which time the bladder wall was investigated histologically. To gain insight into the mechanisms underlying the selective accumulation of EB in malignant urothelium, RNA sequencing of urothelial tissue and subsequent comparative analysis were performed, with a specific focus on cell adhesion. The concentrations of EB were substantially higher in malignant bladders compared with those in healthy bladders, matching the blue staining of the inner bladder wall observed by stereomicroscopy. EB was equally present in the plasma of healthy and tumor-bearing subjects, although at low concentrations. Importantly, EB did not cause any abnormalities in the urothelium after 7 days of repeated instillation in normal rats. RNA sequencing of the urothelium indicated an abnormal expression of several genes related to cell adhesion in malignant urothelium compared with the normal urothelium. Our findings may be important for future clinical developments in the field of diagnostics for bladder cancer. Implementing the more cost-effective protocol of EB

  20. Evans blue-mediated white-light detection of non-muscle-invasive bladder cancer: A preclinical feasibility and safety study using a rat bladder urothelial cell carcinoma model.

    PubMed

    Elsen, Sanne; Lerut, Evelyne; Van Der Aa, Frank; Van Cleynenbreugel, Ben; Van Poppel, Hendrik; De Witte, Peter

    2016-12-01

    Photodynamic diagnosis (PDD) improves the detection of non-muscle-invasive bladder cancer (NMIBC). However, white-light (WL) cystoscopy remains the technique routinely used in urological clinics. A more cost-effective but equally performant alternative to PDD may encompass the use of an intense tumoritropic dye in combination with WL cystoscopy. Using a preclinical setting, we investigated the practical aspects of the use of Evans blue (EB) dye for the possible future detection of NMIBC using WL cystoscopy. A solution of 1 and 5 mM EB was instilled into healthy and AY-27 tumor-bearing rat bladders. The bladders were then rapidly dissected and the inner walls were inspected for EB using WL stereomicroscopy. EB present in the bladders and the plasma was also quantified using high performance liquid chromatography. To assess the effects of repeated instillations on normal rat bladders, EB was instilled for 7 consecutive days, after which time the bladder wall was investigated histologically. To gain insight into the mechanisms underlying the selective accumulation of EB in malignant urothelium, RNA sequencing of urothelial tissue and subsequent comparative analysis were performed, with a specific focus on cell adhesion. The concentrations of EB were substantially higher in malignant bladders compared with those in healthy bladders, matching the blue staining of the inner bladder wall observed by stereomicroscopy. EB was equally present in the plasma of healthy and tumor-bearing subjects, although at low concentrations. Importantly, EB did not cause any abnormalities in the urothelium after 7 days of repeated instillation in normal rats. RNA sequencing of the urothelium indicated an abnormal expression of several genes related to cell adhesion in malignant urothelium compared with the normal urothelium. Our findings may be important for future clinical developments in the field of diagnostics for bladder cancer. Implementing the more cost-effective protocol of EB

  1. Simultaneous multi-analyte urinary protein assay for bladder cancer detection

    PubMed Central

    2014-01-01

    Background The ability to accurately measure multiple proteins simultaneously in a single assay has the potential to markedly improve the efficiency of a myriad of clinical assays. Here, we tested the performance of a new, multiplex protein array platform to quantitate three bladder cancer-associated proteins in urine samples. The following analytes, interleukin 8 (IL8), matrix metallopeptidase 9 (MMP9), and vascular endothelial growth factor A (VEGFA) were monitored using Q-plex, a customized multiplex ELISA system from Quansys Biosciences, and individual target commercial ELISA kits. The performance of the two approaches was compared by evaluating the diagnostic accuracy of the biomarker assays in samples from a cohort of 73 subjects of known bladder cancer status. Results The combination biomarker panel analyses revealed an AUROC value of 0.9476 for the Q-plex assay, and 0.9119 for the combination of the single-target ELISA assays. The Q-plex assay achieved an overall diagnostic sensitivity of 0.93 and specificity of 0.81, and the individual target ELISA assays achieved an overall sensitivity of 0.77 and specificity of 0.91. Conclusion Based on these encouraging preliminary data, we believe that the Q-Plex technology is a viable platform that can be exploited as an efficient, highly accurate tool to quantitate multiplex panels of diagnostic proteins in biologic specimens. PMID:24684904

  2. Bladder cancer epidemiology and genetic susceptibility

    PubMed Central

    Chu, Haiyan; Wang, Meilin; Zhang, Zhengdong

    2013-01-01

    Bladder cancer is the most common malignancy of the urinary system. The incidence of bladder cancer of men is higher than that of women (approximately 4:1). Here, we summarize the bladder cancer-related risk factors, including environmental and genetic factors. In recent years, although the mortality rate induced by bladder cancer has been stable or decreased gradually, the public health effect may be pronounced. The well-established risk factors for bladder cancer are cigarette smoking and occupational exposure. Genetic factors also play important roles in the susceptibility to bladder cancer. A recent study demonstrated that hereditary non-polyposis colorectal cancer is associated with increased risk of bladder cancer. Since 2008, genome-wide association study (GWAS) has been used to identify the susceptibility loci for bladder cancer. Further gene-gene or gene-environment interaction studies need to be conducted to provide more information for the etiology of bladder cancer. PMID:23720672

  3. Genetics Home Reference: bladder cancer

    MedlinePlus

    ... Kozlowski JM. The p53 tumor suppressor gene and nuclear protein: basic science review and relevance in the ... Zwarthoff EC, Radvanyi F. Novel fibroblast growth factor receptor 3 (FGFR3) mutations in bladder cancer previously identified ...

  4. Artemisinins as potential anticancer agents: uptake detection in erythrocytes using Fourier transform infrared spectroscopy and cytotoxicity against bladder cancer cells.

    PubMed

    Humphreys, Charlotte; Cooper, Alan J; Barbu, Eugen; Birch, Brian R; Lwaleed, Bashir A

    2016-05-06

    Semisynthetic derivatives of the antimalarial drug artemisinin may also possess anticancer properties. The ability to detect artemisinin uptake and distribution in cells would facilitate live cell imaging without labelling. This study describes mid-range infrared absorption spectra for three artemisinin variants and attempts to detect their presence in a simple cell model (erythrocytes). Cytotoxicity assays assess potential anticancer properties against bladder cancer cells. Mid-range Fourier transform infrared spectra were obtained from dry preparations of dihydroartemisinin (DHA), artesunate (ART) and artemether (ARTE). Erythrocytes were prepared from normal blood and incubated for 30 min at 37°C with the three artemisinin derivatives. Cytospin preparations were prepared on aluminium foil for spectroscopy. Potential for growth inhibition in the RT112 bladder carcinoma cell line was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide residual viable biomass method. Spectra were obtained from the three native compounds. Repeat scans after 8 weeks showed ART and ARTE to be stable, stored under manufacturer's recommendations. DHA exhibited marked changes over the same period. It was possible by subtraction to detect DHA in cytospins, but not ART or ARTE. The fit between the subtraction spectrum and that of the native compound was >80%. DHA and ART showed strong cytotoxic potential against RT112 cells. The artemisinin derivatives tested exhibit unique mid-range infrared absorption spectra which can be used to monitor degradation and, for DHA, can be detected by subtraction in loaded erythrocytes rendering future imaging studies feasible. Its cytotoxic efficacy against RT112 cells suggests bladder cancer as a possible target disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. Treatment of bladder cancer. Oncology overview

    SciTech Connect

    Not Available

    1982-10-01

    Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Surgical treatment of common bladder cancers; Radiation therapy of common bladder cancers; Chemotherapy of common bladder cancers; Immunotherapy of common bladder cancers; Multimodal treatment of common bladder cancers; Other treatment modalities of common bladder cancers; Treatment of less common bladder cancers; Reviews of treatment of bladder cancers.

  6. 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.

  7. Treatment of superficial bladder cancer.

    PubMed Central

    Morales, A.

    1980-01-01

    Most patients with bladder cancer initially present with localized, potentially curable tumours. Endoscopic surgery offers the best opportunity to eliminate these early lesions, but the rate of tumour recurrence after adequate resection is high (around 70%). Conventional methods of treatment have a place in the management of early bladder neoplasms, but their success rate is still unsatisfactory and they frequently fail to decrease the risk of recurrence. New drugs and more effective forms of administration have enhanced the use of chemotherapeutic agents. Fundamentally different approaches, such as specific immunotherapy, the use of laser energy and photodynamic therapy, are emerging as valuable approaches in the treatment of superficial bladder cancer and the prevention of recurrence. Randomized trials to assess their value and a concerted multidisciplinary effort with combined treatment give hope for effective control of early bladder cancer. PMID:6770987

  8. Treatment of superficial bladder cancer.

    PubMed

    Morales, A

    1980-05-24

    Most patients with bladder cancer initially present with localized, potentially curable tumours. Endoscopic surgery offers the best opportunity to eliminate these early lesions, but the rate of tumour recurrence after adequate resection is high (around 70%). Conventional methods of treatment have a place in the management of early bladder neoplasms, but their success rate is still unsatisfactory and they frequently fail to decrease the risk of recurrence. New drugs and more effective forms of administration have enhanced the use of chemotherapeutic agents. Fundamentally different approaches, such as specific immunotherapy, the use of laser energy and photodynamic therapy, are emerging as valuable approaches in the treatment of superficial bladder cancer and the prevention of recurrence. Randomized trials to assess their value and a concerted multidisciplinary effort with combined treatment give hope for effective control of early bladder cancer.

  9. What Are the Risk Factors for Bladder Cancer?

    MedlinePlus

    ... of bladder cancer in the United States. Personal history of bladder or other urothelial cancer Urothelial carcinomas ... urinary infections and bladder cancer. Genetics and family history People who have family members with bladder cancer ...

  10. Clinical experience with the use of 5-ALA for the detection of superficial bladder cancer

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert G.; Baumgartner, Reinhold; Knuechel, Ruth; Kriegmair, M.; Stepp, H. G.; Zaak, D.; Hofstetter, Alfons G.

    2000-06-01

    We report about the experience obtained in the fluorescence cystoscopic evaluation of 647 patients investigated since 1993. Of all histologically confirmed tumors, 32 percent would have been missed with conventional cystoscopy. Only 16 of 38 CIS were also detected under white light. In patients with entirely normal or unspecifically inflamed appearing mucosa, 44 otherwise invisible malignant lesions could be localized by fluorescence, 16 of them being present in patients with negative bladder washing cytology. The specificity of fluorescence cystoscopy is comparable to white light cystoscopy. A prospective multi-center study was conducted to show, whether a fluorescence controlled transurethral two weeks revealed residual tumor in 53 percent in the white light arm compared to 33 percent in the fluorescence arm. This difference was statistically significant. Of the 33 percent tumor in the fluorescence arm, most was gathered within the resection margins of the first resection, indicating an insufficiently deep resection rather than a failure in detecting the lesion.

  11. Near-IR Fourier transform Raman spectroscopy in surgery and medicine: detection of renal stones and bladder cancer

    NASA Astrophysics Data System (ADS)

    Nie, Shuming; Redd, Douglas C. B.; Li, Yunzhi; Yu, Nai-Teng

    1992-06-01

    Tissue diagnosis and characterization are critically important to the development and applications of laser-based therapeutic procedures in urology (viz., laser lithotripsy and bladder cancer treatment). Recently, we demonstrated for the first time that the new technique of near-infrared laser excited Fourier transform (FT)-Raman spectroscopy can readily differentiate various types of renal stones and bladder cancer from normal kidney/bladder tissues. It has thus become possible to develop an FT-Raman-based fiberoptic sensor for clinical use in laser lithotripsy and bladder cancer treatment. The future development of such a diagnostic modality will allow a surgeon/physician to take real-time Raman spectra of urinary calculi or cancerous tissue via a flexible fiberoptic probe.

  12. Relationship between Schistosomiasis and Bladder Cancer

    PubMed Central

    Mostafa, M. H.; Sheweita, S. A.; O’Connor, P. J.

    1999-01-01

    potential for use as biomarkers in the early detection of bladder cancer that may assist in alleviating the problem. PMID:9880476

  13. Photodynamic management of bladder cancer

    NASA Astrophysics Data System (ADS)

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

    2009-06-01

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

  14. Genetic and Epigenetic Alterations in Bladder Cancer

    PubMed Central

    2016-01-01

    Bladder cancer is one of the most common cancers worldwide, with a high rate of recurrence and poor outcomes as a result of relapse. Bladder cancer patients require lifelong invasive monitoring and treatment, making bladder cancer one of the most expensive malignancies. Lines of evidence increasingly point to distinct genetic and epigenetic alteration patterns in bladder cancer, even between the different stages and grades of disease. In addition, genetic and epigenetic alterations have been demonstrated to play important roles during bladder tumorigenesis. This review will focus on bladder cancer-associated genomic and epigenomic alterations, which are common in bladder cancer and provide potential diagnostic markers and therapeutic targets for bladder cancer treatment. PMID:27915480

  15. Bladder Cancer Risk Prediction Models

    Cancer.gov

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

  16. [Staging urinary bladder cancer with dynamic MR imaging].

    PubMed

    Tsuda, K; Narumi, Y; Nakamura, H; Nonomura, I; Okuyama, A

    2000-11-01

    This article reviews the magnetic resonance (MR) staging of bladder cancer. The multiplanar and soft-tissue characterization capabilities of MR imaging make it a valuable diagnostic tool to image the urinary bladder. Recent advances of MR imaging such as fast imaging, pelvic phased array coil, and dynamic imaging improve the image quality and diagnostic accuracy for staging bladder cancer. Some patient-related factors are also important for optimal imaging of the urinary bladder, especially motion artifacts from the gastrointestinal tract and the degree of bladder distension. An anticholinergic agent should be used for suppressing the motion artifacts. Optimal bladder filling can be achieved by asking patients to void and drink water 1 hour before examinations. Scanning perpendicular to the bladder wall is necessary for optimal evaluation for staging bladder cancer. Oblique scanning is needed in cases when a tumor is not located on the dome, base, anterior wall, posterior wall, or lateral walls. The early phase image of dynamic imaging is most useful for staging tumors. Better contrast between tumor and bladder wall on dynamic images provides high staging accuracy, especially in differentiation between superficial tumors and tumors with muscle invasion. MR imaging is comparable to computed tomography (CT) in the evaluation of lymph nodes. Although MR imaging currently is not appropriate for screening for bladder cancer and detecting small tumors, it has been proved to be most useful in the staging of bladder cancer.

  17. [Occupational hazards and bladder cancer].

    PubMed

    Nizamova, R S

    1991-01-01

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

  18. Immunobiology of human bladder cancer.

    PubMed

    Herr, H W

    1976-02-01

    The immune destruction of bladder cancer most likely results from an interaction of specific and non-specific cellular and humoral responses evoked by tumor-associated antigens. We are just beginning to comprehend the complex immune mechanisms operating to retard or facilitate tumor growth in patients with this disease. This understanding has led to renewed hope that the immune system may be manipulated for the benefit of the tumor-bearing patient. However, only a thorough understanding of the basic functions of the immune system in man will permit a rational approach to immunotherapy in patients with bladder cancer.

  19. Proliposomal Intravesical Paclitaxel for Treatment of Low-Grade, Stage Ta, Non Muscle Invasive Bladder Cancer

    ClinicalTrials.gov

    2017-03-16

    Bladder Cancer Cell Transitional; Non-Muscle Invasive Bladder Cancer; Bladder Cancer; Urinary Bladder; Transitional Cell Carcinoma of the Bladder; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Urinary Bladder Diseases; Urologic Diseases

  20. 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

  1. Hexaminolevulinate hydrochloride in the detection of nonmuscle invasive cancer of the bladder.

    PubMed

    Di Stasi, Savino M; De Carlo, Francesco; Pagliarulo, Vincenzo; Masedu, Francesco; Verri, Cristian; Celestino, Francesco; Riedl, Claus

    2015-12-01

    Clinical trials have shown that hexaminolevulinate (HAL) fluorescence cystoscopy improves the detection of bladder tumors compared with standard white-light cystoscopy, resulting in more efficacious treatment. However, some recent meta-analyses report controversially on recurrence-free rates with this procedure. A systematic review of literature was performed from December 2014 to January 2015 using the PubMed, Embase and Cochrane databases for controlled trials on photodynamic diagnosis (PDD) with HAL. A total of 154 publications were found up to January 2015. Three of the authors separately reviewed the records to evaluate eligibility and methodological quality of clinical trials. A total of 16 publications were considered eligible for analysis. HAL-PDD-guided cystoscopy increased overall tumor detection rate (proportion difference 19%, 95% confidence interval [CI] 0.152-0.236) although the benefit was particularly significant in patients with carcinoma in situ (CIS) lesion (proportion difference 15.7%, 95% CI 0.069-0.245) and was reduced in papillary lesions (Ta proportion difference 5.9%, 95% CI 0.014-0.103 and T1 proportion difference 1.2%, 95% CI 0.033-0.057). Moreover, there were 15% of patients (95% CI 0.098-0.211) with at least one additional tumor seen with PDD. With regard to recurrence rates, the data sample was insufficient for a statistical analysis, although the evaluation of raw data showed a trend in favor of HAL-PDD. This meta-analysis confirms the increased tumor detection rate by HAL-PDD with a most pronounced benefit for CIS lesion.

  2. Hexaminolevulinate hydrochloride in the detection of nonmuscle invasive cancer of the bladder

    PubMed Central

    Di Stasi, Savino M.; De Carlo, Francesco; Pagliarulo, Vincenzo; Masedu, Francesco; Verri, Cristian; Celestino, Francesco; Riedl, Claus

    2015-01-01

    Clinical trials have shown that hexaminolevulinate (HAL) fluorescence cystoscopy improves the detection of bladder tumors compared with standard white-light cystoscopy, resulting in more efficacious treatment. However, some recent meta-analyses report controversially on recurrence-free rates with this procedure. A systematic review of literature was performed from December 2014 to January 2015 using the PubMed, Embase and Cochrane databases for controlled trials on photodynamic diagnosis (PDD) with HAL. A total of 154 publications were found up to January 2015. Three of the authors separately reviewed the records to evaluate eligibility and methodological quality of clinical trials. A total of 16 publications were considered eligible for analysis. HAL–PDD-guided cystoscopy increased overall tumor detection rate (proportion difference 19%, 95% confidence interval [CI] 0.152–0.236) although the benefit was particularly significant in patients with carcinoma in situ (CIS) lesion (proportion difference 15.7%, 95% CI 0.069–0.245) and was reduced in papillary lesions (Ta proportion difference 5.9%, 95% CI 0.014–0.103 and T1 proportion difference 1.2%, 95% CI 0.033–0.057). Moreover, there were 15% of patients (95% CI 0.098–0.211) with at least one additional tumor seen with PDD. With regard to recurrence rates, the data sample was insufficient for a statistical analysis, although the evaluation of raw data showed a trend in favor of HAL–PDD. This meta-analysis confirms the increased tumor detection rate by HAL–PDD with a most pronounced benefit for CIS lesion. PMID:26622319

  3. Obesity, Physical Activity and Bladder Cancer.

    PubMed

    Noguchi, Jonathan L; Liss, Michael A; Parsons, J Kellogg

    2015-10-01

    While smoking and exposure to certain chemicals are well-defined risk factors for bladder cancer, there is no consensus as to the roles of modifiable lifestyle factors, notably physical activity, and obesity. We evaluated associations of obesity and physical activity with bladder cancer risk by performing a system-wide search of PubMed for cohort and case-control studies focused on obesity, exercise, and bladder cancer. A total of 31 studies were identified that evaluated the associations of obesity and physical activity with bladder cancer risk: 20 focused on obesity, eight on physical activity, and three on both. There was marked heterogeneity in population composition and outcomes assessment. Fifteen (65%) of the obesity studies used prevalence or incidence as the primary outcome and seven (30%) used bladder cancer mortality. Ten (44%) observed positive and 13 (56%) null associations of obesity with bladder cancer. Three (100%) of three studies also noted strong positive associations of obesity with bladder cancer progression or recurrence. Ten (91%) of the physical activity studies analyzed prevalence or incidence and one (9%) mortality. One (9%) study observed positive, seven (64%) null, and three (27%) negative associations of physical activity with bladder cancer. Study heterogeneity precluded quantitative assessment of outcomes. Obesity is potentially associated with an increased risk of bladder cancer, particularly for progression, recurrence, or death. Further studies of physical activity and bladder cancer are needed to validate these observations and elucidate the associations of exercise with bladder cancer progression and mortality.

  4. Validation of the diagnostic utility of urinary midkine for the detection of bladder cancer.

    PubMed

    Vu Van, Dana; Heberling, Ulrike; Wirth, Manfred P; Fuessel, Susanne

    2016-11-01

    As it has been demonstrated previously that midkine (also known as neurite growth-promoting factor 2) protein levels in urine of bladder cancer (BCa) patients are increased compared to healthy controls, the present study validated the diagnostic utility of midkine in an independent patient cohort and compared the observed values with voided urine cytology (VUC), which is the current reference standard for non-invasive diagnosis of BCa. Voided urine samples were prospectively collected from 92 BCa patients and 70 control subjects. Protein levels of midkine were assessed using a commercially available enzyme-linked immunosorbent assay and normalized to urinary creatinine. The diagnostic performance of urinary midkine was evaluated by receiver operating characteristic curves. The best combinations of sensitivities and specificities were determined by Youden's Index. Midkine concentrations were significantly elevated in urine samples from BCa patients compared to controls (P<0.001; Mann-Whitney U Test). The level of midkine was associated with disease progression, with the highest concentrations in urine specimens of patients with pT1 and ≥pT2a, as well as high-grade tumors (P<0.001; Mann-Whitney U test). Sensitivities of urinary midkine and VUC were 69.7 and 87.6%, respectively. The corresponding specificities for midkine and VUC were 77.9 and 87.7%, respectively. The combined use of VUC and midkine improved the sensitivity to 93.3%, but reduced the specificity to 66.2%. Despite its reduced discriminatory power for low-grade and low-stage BCa, urinary midkine can be utilized for the identification of high-grade pT1 and ≥pT2a tumors. This means that midkine may potentially be suitable for the identification of patients with high risk BCa.

  5. Detection of multiple mutations in urinary exfoliated cells from male bladder cancer patients at diagnosis and during follow-up

    PubMed Central

    Critelli, Rossana; Fasanelli, Francesca; Oderda, Marco; Polidoro, Silvia; Assumma, Manuela Bianca; Viberti, Clara; Preto, Mirko; Gontero, Paolo; Cucchiarale, Giuseppina; Lurkin, Irene; Zwarthoff, Ellen C.; Vineis, Paolo; Sacerdote, Carlotta; Matullo, Giuseppe; Naccarati, Alessio

    2016-01-01

    Most bladder cancer (BC) patients need life-long, invasive and expensive monitoring and treatment, making it a serious burden on the health system. Thus, there is a pressing need for an accurate test to assist diagnosis and surveillance of BC as an alternative to cystoscopy. Mutations in human TERT, FGFR3, PIK3CA, and RAS genes have been proposed as potential molecular markers in bladder tumor. Their concomitant presence in urine samples has not been fully explored. We investigated a panel of mutations in DNA from exfoliated urinary cells of 255 BC patients at diagnosis. Forty-one mutations in TERT, FGFR3, PIK3CA, and RAS were analyzed by SNaPshot assay in relation to clinical outcome. In 81 of these patients under surveillance, the same set of mutations was screened in additional 324 samples prospectively collected. The most common mutations detected in urine at diagnosis were in the TERT promoter. In non-invasive BC, these mutations were related to high risk and grade (p<0.0001) as well as progression to muscle-invasive disease (p=0.01), whereas FGFR3 mutations were observed in low-grade BC (p=0.02) and patients with recurrences (p=0.05). Stronger associations were observed for combined TERT and FGFR3 mutations and number of recurrences (OR: 4.54 95% CI: 1.23-16.79, p=0.02). Analyses of the area under the curve for combinations of mutations detected at diagnosis and follow-up showed an accuracy of prediction of recurrence of 0.80 (95% CI: 0.71-0.89). Mutations in urine of BC patients may represent reliable biomarkers. In particular, TERT and FGFR3 mutations have a good accuracy of recurrence prediction. PMID:27611947

  6. Low prevalence of HPV detection and genotyping in non-muscle invasive bladder cancer using single-step PCR followed by reverse line blot.

    PubMed

    Pichler, Renate; Borena, Wegene; Schäfer, Georg; Manzl, Claudia; Culig, Zoran; List, Sebastian; Neururer, Sabrina; Von Laer, Dorothee; Heidegger, Isabel; Klocker, Helmut; Horninger, Wolfgang; Steiner, Hannes; Brunner, Andrea

    2015-12-01

    To clarify the role of human papillomavirus (HPV) in non-muscle invasive bladder cancer, HPV-DNA was scrutinized in formalin-fixed, paraffin-embedded (FFPE) bladder cancer tissue using single-step PCR (HPV L1) for HPV detection, followed by reverse line blot (RLB) for genotyping. A total of 186 patients who underwent transurethral resection of the bladder due to primary, non-muscle invasive bladder cancer from 2006 to 2009 were reviewed. A positive control group of 22 cervical tissues with cervical carcinoma was included. Histology confirmed urothelial carcinoma in all patients: primary CIS, pTa, pT1 and pTa + pT1 in 14 (7.5 %), 134 (72 %), 36 (19.4 %) and two (1.1 %) patients, respectively. A total of 119 (63.9 %) of them were classified as low-risk, while 67 (36.1 %) were high-risk cancers. Tumor recurrence and progression (≥pT2) were seen in 79 and 11 patients (mean follow-up 45 months). The presence of HPV-DNA by single-step PCR was detected in four (2.2 %) patients. HPV 16 and HPV 6 were positive in two (1.1 %) and one (0.6 %) patient, respectively In one case, no HPV genotype listed on the RLB assay could be identified. In the control group, the HPV infection rate was 100 %: HPV 16 in 12 (54.6 %) patients, HPV 16/18 in four (18.3 %) patients, HPV 18 in two (9.1 %) patients, HPV 16/45 in one patient (4.5 %), HPV 18/33 in one (4.5 %) patient, HPV 16/33 in one (4.5 %) patient and HPV 33 in one (4.5 %) patient. Our study demonstrates low prevalence of HPV infection in FFPE bladder cancer tissue, arguing against the etiological role of HPV in non-muscle urothelial carcinogenesis.

  7. Bladder cancer: Present and future.

    PubMed

    Martinez Rodriguez, Roberto Hugo; Buisan Rueda, Oscar; Ibarz, Luis

    2017-07-20

    Bladder cancer has a high incidence and involves high associated morbidity and mortality. Since its initial clinical suspicion, early diagnostic confirmation and multimodal treatment involve different medical specialties. For this reason, we consider it important to spread the current consensus for its management. Recent advances in immunology and Chemotherapy make it necessary to expose and reflect on future perspectives. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  8. Identification and validation of AIB1 and EIF5A2 for noninvasive detection of bladder cancer in urine samples.

    PubMed

    Zhou, Bang-Fen; Wei, Jin-Huan; Chen, Zhen-Hua; Dong, Pei; Lai, Ying-Rong; Fang, Yong; Jiang, Hui-Ming; Lu, Jun; Zhou, Fang-Jian; Xie, Dan; Luo, Jun-Hang; Chen, Wei

    2016-07-05

    We previously demonstrated that amplified in breast cancer 1 (AIB1) and eukaryotic initiation factor 2 (EIF5A2) overexpression was an independent predictor of poor clinical outcomes for patients with bladder cancer (BCa). In this study, we evaluated the usefulness of AIB1 and EIF5A2 alone and in combination with nuclear matrix protein 22 (NMP22) as noninvasive diagnostic tests for BCa. Using urine samples from 135 patients (training set, controls [n = 50] and BCa [n = 85]), we detected the AIB1, EIF5A2, and NMP22 concentrations using enzyme-linked immunosorbent assay. We applied multivariate logistic regression analysis to build a model based on the three biomarkers for BCa diagnosis. The diagnostic accuracy of the three biomarkers and the model were assessed and compared by the area under the curve (AUC) of the receiver operating characteristic. We validated the diagnostic accuracy of these biomarkers and the model in an independent validation cohort of 210 patients. In the training set, urinary concentrations of AIB1, EIF5A2, and NMP22 were significantly elevated in BCa. The AUCs of AIB1, EIF5A2, NMP22, and the model were 0.846, 0.761, 0.794, and 0.919, respectively. The model had the highest diagnostic accuracy when compared with AIB1, EIF5A2, or NMP22 (p < 0.05 for all). The model had 92% sensitivity and 92% specificity. We obtained similar results in the independent validation cohort. AIB1 and EIF5A2 show promise for the noninvasive detection of BCa. The model based on AIB1, EIF5A2, and NMP22 outperformed each of the three individual biomarkers for detecting BCa.

  9. [The latest news on bladder cancer].

    PubMed

    Retz, M; Lehmann, J; Nawroth, R; Gschwend, J E

    2007-07-01

    A review of the current literature provides new scientific insights into the diagnosis, prognosis and novel molecular targets for bladder cancer. The new WHO classification refines our staging system and influences treatment options. International clinical databases provide new tools for calculating the individual risk for bladder cancer recurrence and progression. Systematic gene cluster analysis defines multimarker panels that can serve as robust predictors of outcome. Discoveries of new signaling pathways in bladder cancer are leading to novel molecular targets for innovative therapies.

  10. Hair dye use and risk of bladder cancer in the New England bladder cancer study.

    PubMed

    Koutros, Stella; Silverman, Debra T; Baris, Dalsu; Zahm, Shelia Hoar; Morton, Lindsay M; Colt, Joanne S; Hein, David W; Moore, Lee E; Johnson, Alison; Schwenn, Molly; Cherala, Sai; Schned, Alan; Doll, Mark A; Rothman, Nathaniel; Karagas, Margaret R

    2011-12-15

    Aromatic amine components in hair dyes and polymorphisms in genes that encode enzymes responsible for hair dye metabolism may be related to bladder cancer risk. We evaluated the association between hair dye use and bladder cancer risk and effect modification by N-acetyltransferase-1 (NAT1), NAT2, glutathione S-transferase Mu-1 (GSTM1) and glutathione S-transferase theta-1 (GSTT1) genotypes in a population-based case-control study of 1193 incident cases and 1418 controls from Maine, Vermont and New Hampshire enrolled between 2001 and 2004. Individuals were interviewed in person using a computer-assisted personal interview to assess hair dye use and information on potential confounders and effect modifiers. No overall association between age at first use, year of first use, type of product, color, duration or number of applications of hair dyes and bladder cancer among women or men was apparent, but increased risks were observed in certain subgroups. Women who used permanent dyes and had a college degree, a marker of socioeconomic status, had an increased risk of bladder cancer [odds ratio (OR) = 3.3, 95% confidence interval (CI): 1.2-8.9]. Among these women, we found an increased risk of bladder cancer among exclusive users of permanent hair dyes who had NAT2 slow acetylation phenotype (OR = 7.3, 95% CI: 1.6-32.6) compared to never users of dye with NAT2 rapid/intermediate acetylation phenotype. Although we found no relation between hair dye use and bladder cancer risk in women overall, we detected evidence of associations and gene-environment interaction with permanent hair dye use; however, this was limited to educated women. These results need confirmation with larger numbers, requiring pooling data from multiple studies. Copyright © 2011 UICC.

  11. Transcripts of circulating tumor cells detected by a breast cancer-specific platform correlate with clinical stage in bladder cancer patients.

    PubMed

    Todenhöfer, Tilman; Hennenlotter, Jörg; Dorner, Nathalie; Kühs, Ursula; Aufderklamm, Stefan; Rausch, Steffen; Bier, Simone; Mischinger, Johannes; Schellbach, Doreen; Hauch, Siegfried; Feniuk, Natalie; Bedke, Jens; Gakis, Georgios; Stenzl, Arnulf; Schwentner, Christian

    2016-05-01

    There is increasing interest in circulating tumor cells (CTCs) as a biomarker in bladder cancer (BC). In the present pilot study, we used a platform originally developed for detection of breast cancer CTCs to assess breast cancer-associated transcripts in CTCs of patients with different stages of BC. Moreover, transcripts specific for cancer stem cells and epithelial mesenchymal transition (EMT) were assessed. We prospectively enrolled 83 BC patients and 29 controls. The AdnaTest® system was used to enrich epithelial cells in peripheral blood and to detect breast cancer-associated, stem cell-specific or EMT-specific transcripts. Test results were correlated with clinical and pathological stage. A positive AdnaTest® BreastCancerDetect was present in 6.9 % of controls (group A), 6.7, 15.0 and 18.7 % of patients with non-muscle-invasive BC (B), cM0 muscle-invasive BC (C) and metastatic BC (D) (p = 0.13). Stem cell-specific transcripts in group A, B, C and D were detected in 10.3, 10.0, 22.5 and 31.3 % (p = 0.03). EMT-associated transcripts were present in 3.5, 3.3, 15.0 and 18.7 % (p = 0.03). In group C, epithelial and stem-like transcripts correlated with tumor stage (p = 0.01 and 0.04). CTCs with expression of breast cancer-associated transcripts are present in a considerable proportion of patients with BC. EMT and stem cell-specific transcripts of CTCs correlate with clinical stage and can be detected in patients negative for epithelial transcripts. The prognostic relevance of AdnaTest® results in BC patients and potential implications for therapy decisions remain to be determined in prospective studies.

  12. 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

  13. 18F-FDG PET/CT in Bladder Cancer.

    PubMed

    Tagliabue, Luca; Russo, Giovanna; Lucignani, Giovanni

    2016-12-01

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

  14. 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.

  15. Detection of bladder cancer: comparison of low-dose scans with AIDR 3D and routine-dose scans with FBP on the excretory phase in CT urography

    PubMed Central

    Tsuboyama, Takahiro; Kumano, Seishi; Inada, Yuki; Koyama, Mitsuhiro; Azuma, Haruhito; Narumi, Yoshifumi

    2016-01-01

    Objective: To prospectively compare the detection of bladder cancer between low-dose scans with adaptive iterative dose reduction three dimensional projection (AIDR 3D) and routine-dose scans with filtered back projection (FBP) on the excretory phase (EP) in CT urography. Methods: 42 patients were included. Routine- and low-dose EP were performed in each patient. Routine-dose images were reconstructed with FBP, and low-dose images were reconstructed with AIDR 3D. Two radiologists scored confidence levels for the presence or absence of bladder cancer using a 5-point scale. The CT dose index of each EP was measured, and the dose reduction was calculated. Results: Sensitivity, specificity and accuracy were 86.4%, 95.0% and 90.5% on routine-dose scans and were 86.4%, 90.0% and 88.1% on low-dose scans, respectively. There was no significant difference (p; not significant, 1.00 and 1.00, respectively). The average CT dose index was 8.07 and 2.63 mGy on routine- and low-dose scans, and the ratio of dose reduction was 67.6%. Conclusion: The detection of bladder cancer on low-dose scans with AIDR 3D is almost equal to that on routine-dose scans with FBP on the EP, with nearly 70% dose reduction. Advances in knowledge: Using AIDR 3D, the radiation dose may be reduced on the EP in CT urography for the detection of bladder cancer. PMID:26642306

  16. Diagnosis of bladder cancer by immunocytochemical detection of minichromosome maintenance protein-2 in cells retrieved from urine.

    PubMed

    Saeb-Parsy, K; Wilson, A; Scarpini, C; Corcoran, M; Chilcott, S; McKean, M; Thottakam, B; Rai, B; Nabi, G; Rana, D; Perera, M; Stewart, K; Laskey, R A; Neal, D E; Coleman, N

    2012-10-09

    We tested the accuracy of immunocytochemistry (ICC) for minichromosome maintenance protein-2 (MCM-2) in diagnosing bladder cancer, using cells retrieved from urine. Adequate samples were obtained from 497 patients, the majority presenting with gross haematuria (GH) or undergoing cystoscopic surveillance (CS) following previous bladder cancer. We performed an initial study of 313 patients, followed by a validation study of 184 patients. In all cases, presence/absence of bladder cancer was established by cystoscopy/biopsy. In the initial study, receiver operator characteristic analysis showed an area under the curve of 0.820 (P<0.0005) for the GH group and 0.821 (P<0.01) for the CS group. Optimal sensitivity/specificity were provided by threshold values of 50+ MCM-2-positive cells in GH samples and 200+ cells in CS samples, based on a minimum total cell number of 5000. Applying these thresholds to the validation data set gave 81.3% sensitivity, 76.0% specificity and 92.7% negative predictive value (NPV) in GH and 63.2% sensitivity, 89.9% specificity and 89.9% NPV in CS. Minichromosome maintenance protein-2 ICC provided clinically relevant improvements over urine cytology, with greater sensitivity in GH and greater specificity in CS (P=0.05). Minichromosome maintenance protein-2 ICC is a reproducible and accurate test that is suitable for both GH and CS patient groups.

  17. Urine BLCA-4 exerts potential role in detecting patients with bladder cancers: a pooled analysis of individual studies

    PubMed Central

    Cai, Qiliang; Wu, Yudong; Guo, Zhanjun; Gong, Rui; Tang, Yang; Yang, Kuo; Li, Xiaodong; Guo, Xuemei; Niu, Yuanjie; Zhao, Yan

    2015-01-01

    Epidemiological studies have explored the diagnostic effect of urine BLCA-4 in bladder cancer. However, the results remain controversial. Therefore, we conducted this pooled analyses to determine the overall accuracy of urine BLCA-4 in bladder cancer. A comprehensive electronic and hand search was conducted for related literatures though several databases. QUADAS-2 was used to assess the quality of each included studies. Diagnostic parameters were calculated using Meta-Disc (version 1.4) and Stata (version 12.0) software. Nine published articles with 1,119 subjects were included. The summary estimates were: sensitivity 0.93 (95% confidence interval [CI] = 0.90-0.95), specificity 0.97 (95% CI, 0.95-0.98), positive likelihood ratio 48.16 (95% CI, 11.77-197.01), negative likelihood ratio 0.08 (95% CI, 0.06-0.11), diagnostic odds ratio 534.03 (95% CI, 150.15-1899.31), and the AUC was 0.9607. In conclusion, urine BLCA-4 is a promising marker in diagnosing bladder cancer. PMID:26462026

  18. Methylation of a panel of microRNA genes is a novel biomarker for detection of bladder cancer.

    PubMed

    Shimizu, Takashi; Suzuki, Hiromu; Nojima, Masanori; Kitamura, Hiroshi; Yamamoto, Eiichiro; Maruyama, Reo; Ashida, Masami; Hatahira, Tomo; Kai, Masahiro; Masumori, Naoya; Tokino, Takashi; Imai, Kohzoh; Tsukamoto, Taiji; Toyota, Minoru

    2013-06-01

    Dysregulation of microRNAs (miRNAs) has been implicated in bladder cancer (BCa), although the mechanism is not fully understood. We aimed to explore the involvement of epigenetic alteration of miRNA expression in BCa. Two BCa cell lines (T24 and UM-UC-3) were treated with 5-aza-2'-deoxycytidine (5-aza-dC) and 4-phenylbutyric acid (PBA), after which their miRNA expression profiles were analyzed using a TaqMan array (Life Technologies, Carlsbad, CA, USA). Bisulfite pyrosequencing was used to assess miRNA gene methylation in 5 cancer cell lines, 83 primary tumors, and 120 preoperative and 47 postoperative urine samples. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of the miRNA gene panel. Of 664 miRNAs examined, 146 were upregulated by 5-aza-dC plus PBA. CpG islands were identified in the proximal upstream of 23 miRNA genes, and 12 of those were hypermethylated in cell lines. Among them, miR-137, miR-124-2, miR-124-3, and miR-9-3 were frequently and tumor-specifically methylated in primary cancers (miR-137: 68.7%; miR-124-2: 50.6%; miR-124-3: 65.1%; miR-9-3: 45.8%). Methylation of the same four miRNAs in urine specimens enabled BCa detection with 81% sensitivity and 89% specificity; the area under the ROC curve was 0.916. Ectopic expression of silenced miRNAs in BCa cells suppressed growth and cell invasion. Our results indicate that epigenetic silencing of miRNA genes may be involved in the development of BCa and that methylation of miRNA genes could be a useful biomarker for cancer detection. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  19. 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.

  20. [Development of noninvasive bladder cancer diagnosis on basis of telomerase and it's subunits hTERT and hTR detection].

    PubMed

    Glukhov, A I; Grigorieva, Y E; Gordeev, S A; Vinarov, A Z; Potoldykova, N V

    2015-01-01

    Telomerase activity (TA) and expression of genes coding it's subunits (hTERT and hTR) have been examined in tumor tissue and urine sediment samples taken from patients with bladder cancer (BC) using the modified TRAP assay (in the case of telomerase detection) and RT-PCR (in the case of hTERT and hTR expression). Results obtained in this study demonstrate possibility of noninvasive diagnosis of BC with sensitivity of 96% and specificity of 100% in the case of telomerase detection and with sensitivity of 80% and specificity of 100% in the case of hTERT detection in urine sediment samples.

  1. Urinary Bladder Cancer in Yemen

    PubMed Central

    Al-Samawi, Abdullah Saleh; Aulaqi, Saleh Mansoor

    2013-01-01

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

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

    PubMed

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

    2012-06-01

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

  3. Combined use of epithelial membrane antigen and nuclear matrix protein 52 as sensitive biomarkers for detection of bladder cancer.

    PubMed

    Attallah, Abdelfattah M; El-Far, Mohamed; Abdallah, Sanaa O; El-Waseef, Ahmed M; Omran, Mohamed M; Abdelrazek, Mohamed A; Attallah, Ahmed A; Saadh, Mohamed J; Radwan, Mohamed; El-waffaey, Kholoud A; Abol-Enei, Hassan

    2015-11-11

    The advent of noninvasive urine-based markers as well as other novel modalities has yielded improved diagnostic accuracy. However, the new markers failed to reach higher sensitivity and specificity. We therefore evaluated the potential role of epithelial membrane antigen (EMA) and nuclear matrix protein 52 (NMP-52) singly and combined as noninvasive biomarkers for the detection of bladder cancer (BC). A total of 160 individuals including 66 patients with BC, 54 patients with benign urologic disorders and 40 healthy volunteers were investigated. Urinary EMA at 130 kDa and NMP at 52 kDa were identified, purified and quantified by Western blot, electroelution and enzyme-linked immunosorbent assay (ELISA). The diagnostic performance of each biomarker and their combination were compared using area under receiver operating characteristic curves (AUC). Mean urinary EMA, 2.42 µg/mL, and NMP-52, 17.85 µg/mL, were significantly elevated in patients with BC compared to controls, 1.18 and 3.44 µg/mL, respectively (p<0.0001). The combined use of these markers yielded values which were increased 4.4- and 13.7-fold in the benign and malignant disease groups, respectively, with respect to the normal group. The values of EMA and NMP-52 were significantly higher in patients with higher-grade tumors than those with lower-grade tumors (p<0.0001). Moreover, this combination could predict all BC stages and grades with 0.91 AUC, 94% sensitivity and 80% specificity. EMA and NMP-52 in combination could be promising noninvasive biomarkers for BC detection.

  4. 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.

  5. Diagnostics techniques in nonmuscle invasive bladder cancer

    PubMed Central

    Soubra, Ayman; Risk, Michael C.

    2015-01-01

    Introduction: Nonmuscle invasive bladder cancer (NMIBC) is the most common presentation of bladder cancer and is often treatable with endoscopic resection and intravesical therapies. Cystoscopy and urine cytology are the gold standard in diagnosis and surveillance but are limited by their sensitivity in some situations. We seek to provide an overview of recent additions to the diagnostic armamentarium for urologists treating this disease. Methods: Articles were identified through a literature review of articles obtained through PubMed searches including the terms “bladder cancer” and various diagnostic techniques described in the article. Results: A variety of urinary biomarkers are available to assist the diagnosis and management of patients with NMIBC. Many have improved sensitivity over urine cytology, but less specificity. There are certain situations in which this has proved valuable, but as yet these are not part of the standard guidelines for NMIBC. Fluorescence cystoscopy has level 1 evidence demonstrating increased rates of tumor detection and prolonged recurrence-free survival when utilized for transurethral resection. Other technologies seeking to enhance cystoscopy, such as narrow band imaging, confocal laser endomicroscopy, and optical coherence tomography are still under evaluation. Conclusions: A variety of urine biomarker and adjunctive endoscopic technologies have been developed to assist the management of NMIBC. While some, such as fluorescence cystoscopy, have demonstrated a definite benefit in this disease, others are still finding their place in the diagnosis and treatment of this disease. Future studies should shed light on how these can be incorporated to improve outcomes in NMIBC. PMID:26604438

  6. Elective bladder-sparing treatment for muscle invasive bladder cancer.

    PubMed

    Lendínez-Cano, G; Rico-López, J; Moreno, S; Fernández Parra, E; González-Almeida, C; Camacho Martínez, E

    2014-01-01

    Radical cystectomy is the standard treatment for localised muscle invasive bladder cancer (MIBC). We offer a bladder-sparing treatment with TURB +/- Chemotherapy+Radiotherapy to selected patients as an alternative. We analyze, retrospectively, 30 patients diagnosed with MIBC from March 1991 to October 2010. The mean age was 62.7 years (51-74). All patients were candidates for a curative treatment, and underwent strict selection criteria: T2 stage, primary tumor, solitary lesion smaller than 5cm with a macroscopic disease-free status after TURB, negative random biopsy without hydronephrosis. Staging CT evaluation was normal. Restaging TURB or tumor bed biopsy showed a disease-free status or microscopic muscle invasion. 14 patients underwent TURB alone, 13 TURB+Chemotherapy and 3 TURB+Chemotherapy+Radiotherapy. The mean follow up was 88.7 months (19-220). 14 patients remained disease free (46.6%), 10 had recurrent non-muscle invasive bladder cancer (33%). 81.3% complete clinical response. 71% bladder preserved at 5-years. Overall, 5-years survival rate was 79% and 85% cancer-specific survival rate. Although radical cystectomy is the standard treatment for localised MIBC, in strictly selected cases, bladder-sparing treatment offers an alternative with good long term results. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  7. Highly specific urine-based marker of bladder cancer.

    PubMed

    Van Le, Thu-Suong; Miller, Raymond; Barder, Timothy; Babjuk, Marko; Potter, Douglas M; Getzenberg, Robert H

    2005-12-01

    Bladder cancer represents a major health problem throughout the world, but advances in tumor biomarker development are revolutionizing how physicians diagnose the disease. We previously used an indirect immunoassay to demonstrate that the bladder cancer specific biomarker, BLCA-4, is present in urine samples from patients with bladder cancer, but not in samples from healthy individuals. In this study, a sandwich immunoassay was used to measure BLCA-4 in urine samples from patient populations with various urologic conditions and healthy individuals. Urine was collected from healthy individuals and from patients with bladder cancer, benign urologic conditions, or prostate cancer. BLCA-4 levels were evaluated by a sandwich immunoassay using two antibodies directed against distinct epitopes on BLCA-4. Using a prospectively determined cutoff of an absorbance unit (OD) of 0.04, 67 of the 75 samples from patients with bladder cancer were positive for BLCA-4, resulting in an assay sensitivity of 89%. Also, 62 of the 65 samples from individuals without bladder cancer were negative for BLCA-4, resulting in an assay specificity of 95%. The high sensitivity and specificity of the sandwich BLCA-4 immunoassay may allow for earlier detection and treatment of disease, thus greatly improving patient care.

  8. Neoadjuvant chemotherapy for bladder cancer.

    PubMed

    Black, Peter C; Brown, Gordon A; Grossman, H Barton; Dinney, Colin P

    2006-11-01

    The 30-45% failure rate after radical cystoprostatectomy mandates that we explore and optimize multimodal therapy to achieve better disease control in these patients. Cisplatin-based multi-agent combination chemotherapy has been used with success in metastatic disease and has therefore also been introduced in patients with high-risk but non-metastatic bladder cancer. There is now convincing evidence that chemotherapy given pre-operatively can improve survival in these patients. In this review we establish the need for peri-operative chemotherapy in bladder cancer patients and summarize the evidence for the efficacy of neoadjuvant chemotherapy. The advantages and disadvantages of neoadjuvant versus adjuvant chemotherapy are discussed, and the main shortcomings of both--treatment-related toxicity and the inability to prospectively identify likely responders--are presented. Finally, a risk-adapted approach to neoadjuvant chemotherapy is presented, whereby the highest risk patients are offered treatment while those unlikely to benefit are spared the treatment-related toxicity.

  9. The Danish Bladder Cancer Database

    PubMed Central

    Hansen, Erik; Larsson, Heidi; Nørgaard, Mette; Thind, Peter; Jensen, Jørgen Bjerggaard

    2016-01-01

    Aim of database The aim of the Danish Bladder Cancer Database (DaBlaCa-data) is to monitor the treatment of all patients diagnosed with invasive bladder cancer (BC) in Denmark. Study population All patients diagnosed with BC in Denmark from 2012 onward were included in the study. Results presented in this paper are predominantly from the 2013 population. Main variables In 2013, 970 patients were diagnosed with BC in Denmark and were included in a preliminary report from the database. A total of 458 (47%) patients were diagnosed with non-muscle-invasive BC (non-MIBC) and 512 (53%) were diagnosed with muscle-invasive BC (MIBC). A total of 300 (31%) patients underwent cystectomy. Among the 135 patients diagnosed with MIBC, who were 75 years of age or younger, 67 (50%) received neoadjuvent chemotherapy prior to cystectomy. In 2013, a total of 147 patients were treated with curative-intended radiation therapy. Descriptive data One-year mortality was 28% (95% confidence interval [CI]: 15–21). One-year cancer-specific mortality was 25% (95% CI: 22–27%). One-year mortality after cystectomy was 14% (95% CI: 10–18). Ninety-day mortality after cystectomy was 3% (95% CI: 1–5) in 2013. One-year mortality following curative-intended radiation therapy was 32% (95% CI: 24–39) and 1-year cancer-specific mortality was 23% (95% CI: 16–31) in 2013. Conclusion This preliminary DaBlaCa-data report showed that the treatment of MIBC in Denmark overall meet high international academic standards. The database is able to identify Danish BC patients and monitor treatment and mortality. In the future, DaBlaCa-data will be a valuable data source and expansive observational studies on BC will be available. PMID:27822081

  10. Metabolomics in bladder cancer: a systematic review

    PubMed Central

    Cheng, Yidong; Yang, Xiao; Deng, Xiaheng; Zhang, Xiaolei; Li, Pengchao; Tao, Jun; Qin, Chao; Wei, Jifu; Lu, Qiang

    2015-01-01

    Bladder cancer (BC) is the most common urological malignancy. Early diagnosis of BC is crucial to improve patient outcomes. Currently, metabolomics is a potential technique that can be used to detect BC. We reviewed current publications and synthesised the findings on BC and metabolomics, i.e. metabolite upregulation and downregulation. Fourteen metabolites (lactic acid, leucine, valine, phenylalanine, glutamate, histidine, aspartic acid, tyrosine, serine, uracil, hypoxanthine, carnitine, pyruvic acid and citric acid) were identified as potential biomarkers for BC. In conclusion, this systematic review presents new opportunities for the diagnosis of BC. PMID:26379905

  11. Risk of Bladder Cancer Among Diabetic Patients Treated With Pioglitazone

    PubMed Central

    Lewis, James D.; Ferrara, Assiamira; Peng, Tiffany; Hedderson, Monique; Bilker, Warren B.; Quesenberry, Charles P.; Vaughn, David J.; Nessel, Lisa; Selby, Joseph; Strom, Brian L.

    2011-01-01

    OBJECTIVE Some preclinical in vivo studies and limited human data suggest a possible increased risk of bladder cancer with pioglitazone therapy. This is an interim report of an ongoing cohort study examining the association between pioglitazone therapy and the risk of bladder cancer in patients with diabetes. RESEARCH DESIGN AND METHODS This study includes 193,099 patients in the Kaiser Permanente Northern California diabetes registry who were ≥40 years of age between 1997 and 2002. Those with prior bladder cancer were excluded. Ever use of each diabetes medication (defined as two or more prescriptions within 6 months) was treated as a time-dependent variable. Cox regression–generated hazard ratios (HRs) compared pioglitazone use with nonpioglitazone use adjusted for age, sex, race/ethnicity, diabetes medications, A1C, heart failure, household income, renal function, other bladder conditions, and smoking. RESULTS The group treated with pioglitazone comprised 30,173 patients. There were 90 cases of bladder cancer among pioglitazone users and 791 cases of bladder cancer among nonpioglitazone users. Overall, ever use of pioglitazone was not associated with risk of bladder cancer (HR 1.2 [95% CI 0.9–1.5]), with similar results in men and women (test for interaction P = 0.8). However, in the a priori category of >24 months of therapy, there was an increased risk (1.4 [1.03–2.0]). Ninety-five percent of cancers diagnosed among pioglitazone users were detected at early stage. CONCLUSIONS In this cohort of patients with diabetes, short-term use of pioglitazone was not associated with an increased incidence of bladder cancer, but use for more than 2 years was weakly associated with increased risk. PMID:21447663

  12. Arsenic exposure and bladder cancer: quantitative assessment of studies in human populations to detect risks at low doses.

    PubMed

    Tsuji, Joyce S; Alexander, Dominik D; Perez, Vanessa; Mink, Pamela J

    2014-03-20

    While exposures to high levels of arsenic in drinking water are associated with excess cancer risk (e.g., skin, bladder, and lung), exposures at lower levels (e.g., <100-200 µg/L) generally are not. Lack of significant associations may result from methodological issues (e.g., inadequate statistical power, exposure misclassification), or a different dose-response relationship at low exposures, possibly associated with a toxicological mode of action that requires a sufficient dose for increased tumor formation. The extent to which bladder cancer risk for low-level arsenic exposure can be statistically measured by epidemiological studies was examined using an updated meta-analysis of bladder cancer risk with data from two new publications. The summary relative risk estimate (SRRE) for all nine studies was elevated slightly, but not significantly (1.07; 95% confidence interval [CI]: 0.95-1.21, p-Heterogeneity [p-H]=0.543). The SRRE among never smokers was 0.85 (95% CI: 0.66-1.08, p-H=0.915), whereas the SRRE was positive and more heterogeneous among ever smokers (1.18; 95% CI: 0.97-1.44, p-H=0.034). The SRRE was statistically significantly lower than relative risks predicted for never smokers in the United States based on linear extrapolation of risks from higher doses in southwest Taiwan to arsenic water exposures >10 µg/L for more than one-third of a lifetime. By contrast, for all study subjects, relative risks predicted for one-half of lifetime exposure to 50 µg/L were just above the upper 95% CI on the SRRE. Thus, results from low-exposure studies, particularly for never smokers, were statistically inconsistent with predicted risk based on high-dose extrapolation. Additional studies that better characterize tobacco use and stratify analyses of arsenic and bladder cancer by smoking status are necessary to further examine risks of arsenic exposure for smokers.

  13. 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

  14. Blindness in a bladder cancer patient.

    PubMed

    Remón, J; Guardeño, R; Badía, A; Cardona, T; Picaza, J M; Lianes, P

    2007-02-01

    Blindness is an unusual symptom in the clinical course of cancer. When it appears it is necessary to differentiate between benign and malign causes. Brain metastases in bladder cancer are extremely rare. MRI is the best diagnostic option. We present a deaf-and-dumb male with subacute blindness, 12 months after the diagnosis of a metastatic bladder cancer. Computerised tomography scan and MRI revealed a mass into the pituitary gland and sella, probably of metastatic origin.

  15. Lymphatic vessel density and function in experimental bladder cancer

    PubMed Central

    Saban, Marcia R; Towner, Rheal; Smith, Nataliya; Abbott, Andrew; Neeman, Michal; Davis, Carole A; Simpson, Cindy; Maier, Julie; Mémet, Sylvie; Wu, Xue-Ru; Saban, Ricardo

    2007-01-01

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

  16. Gemcitabine, Paclitaxel, Doxorubicin in Metastatic or Unresectable Bladder Cancer With Decreased Kidney Function

    ClinicalTrials.gov

    2015-06-19

    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

  17. Bladder cancer clusters in Florida: identifying populations at risk.

    PubMed

    Nieder, Alan M; MacKinnon, Jill A; Fleming, Lora E; Kearney, Greg; Hu, Jennifer J; Sherman, Recinda L; Huang, Youjie; Lee, David J

    2009-07-01

    Modifiable risk factors for bladder cancer have been identified, ie tobacco and chemical exposure. We identified high risk bladder cancer areas and risk factors associated with bladder cancer clusters in Florida using individual and area based data. Spatial modeling was applied to 23,266 early and advanced bladder cancer cases diagnosed between 1998 and 2002 in Florida to identify areas of excess bladder cancer risk. Multivariable regression was used to determine whether sociodemographic indicators, smoking history and proximity to known arsenic contaminated drinking water well sites were associated with bladder cancer diagnosis in a specific area (cluster). A total of 25 clusters were found to have a higher than expected bladder cancer rate, including 13 and 12 of early and late stage disease, respectively. Urban white patients were more likely to live in an advanced bladder cancer cluster. Advanced bladder cancer cluster membership was associated with living in close proximity to known arsenic contaminated drinking water wells. There are multiple areas of early and late stage bladder cancer clusters in Florida. Individuals in an advanced bladder cancer cluster tended to live close to arsenic contaminated wells. Increased evaluation of potentially contaminated well water is warranted in these high risk areas. Targeted bladder cancer public awareness campaigns, smoking cessation support and potentially targeted screening should also be considered in communities at increased risk for bladder cancer. Our analytical approach can also be used by others to systematically identify communities at high risk for bladder and other cancers.

  18. Lab in a Tube: Sensitive Detection of MicroRNAs in Urine Samples from Bladder Cancer Patients Using a Single-Label DNA Probe with AIEgens.

    PubMed

    Min, Xuehong; Zhuang, Yuan; Zhang, Zhenyu; Jia, Yongmei; Hakeem, Abdul; Zheng, Fuxin; Cheng, Yong; Tang, Ben Zhong; Lou, Xiaoding; Xia, Fan

    2015-08-05

    We demonstrate an ultrasensitive microRNA detection method based on an extremely simple probe with only fluorogens but without quencher groups. It avoids complex and difficult steps to accurately design the relative distance between the fluorogens and quencher groups in the probes. Furthermore, the assay could accomplish various detection limits by tuning the reaction temperature due to the different activity of exonuclease III corresponding to the diverse temperature. Specifically, 1 pM miR-21 can be detected in 40 min at 37 °C, and 10 aM (about 300 molecules in 50 μL) miR-21 could be discriminated in 7 days at 4 °C. The great specificity of the assay guarantees that the real 21 urine samples from the bladder cancer patients are successfully detected by our method.

  19. Functional characterization of the bladder cancer marker, BLCA-4.

    PubMed

    Van Le, Thu-Suong; Myers, Julie; Konety, Badrinath R; Barder, Timothy; Getzenberg, Robert H

    2004-02-15

    Bladder cancer is a common disease of the genitourinary tract for which the development of a noninvasive detection technique would have a significant impact on disease management. One of our previously identified bladder cancer-specific proteins, BLCA-4, appears to be associated with a "field effect" of the disease, and in clinical trials is able to separate individuals with bladder cancer from those without the disease with high sensitivity and specificity. The potential clinical utility of this marker has led to the analysis of its function in bladder cancer pathobiology. To additionally analyze the specificity of this marker, the expression in the urine of a variety of benign urologic conditions was analyzed. After cloning the gene encoding BLCA-4, functional aspects of the protein were analyzed by overexpressing it in cell systems, as well as its interaction with other transcription factors and in gel mobility shift assays. Finally, to determine the timing of expression in relation to the observance of bladder cancer, an animal model of the disease was examined. Expression of BLCA-4, the cDNA of which reveals that it is a novel member of the ETS transcription factor family, is not found in benign urologic conditions. Overexpression leads to increased growth rates of cells, and the protein interacts with other transcription factors. In vivo studies reveal that BLCA-4 expression occurs significantly before the observance of grossly visible tumors in an animal model of the disease. BLCA-4 is a bladder cancer marker that is highly specific and occurs early in the development of the disease. It appears to be a transcription factor that may play a role in the regulation of the gene expression in bladder cancer. BLCA-4 is a marker with significant clinical utility that may have an active role in the disease.

  20. Filtration Device for On-Site Collection, Storage and Shipment of Cells from Urine and Its Application to DNA-Based Detection of Bladder Cancer.

    PubMed

    Andersson, Elin; Dahmcke, Christina M; Steven, Kenneth; Larsen, Louise K; Guldberg, Per

    2015-01-01

    Molecular analysis of cells from urine provides a convenient approach to non-invasive detection of bladder cancer. The practical use of urinary cell-based tests is often hampered by difficulties in handling and analyzing large sample volumes, the need for rapid sample processing to avoid degradation of cellular content, and low sensitivity due to a high background of normal cells. We present a filtration device, designed for home or point-of-care use, which enables collection, storage and shipment of urinary cells. A special feature of this device is a removable cartridge housing a membrane filter, which after filtration of urine can be transferred to a storage unit containing an appropriate preserving solution. In spiking experiments, the use of this device provided efficient recovery of bladder cancer cells with elimination of >99% of excess smaller-sized cells. The performance of the device was further evaluated by DNA-based analysis of urinary cells collected from 57 patients subjected to transurethral resection following flexible cystoscopy indicating the presence of a tumor. All samples were tested for FGFR3 mutations and seven DNA methylation markers (BCL2, CCNA1, EOMES, HOXA9, POU4F2, SALL3 and VIM). In the group of patients where a transitional cell tumor was confirmed at histopathological evaluation, urine DNA was positive for one or more markers in 29 out of 31 cases (94%), including 19 with FGFR3 mutation (61%). In the group of patients with benign histopathology, urine DNA was positive for methylation markers in 13 out of 26 cases (50%). Only one patient in this group was positive for a FGFR3 mutation. This patient had a stage Ta tumor resected 6 months later. The ability to easily collect, store and ship diagnostic cells from urine using the presented device may facilitate non-invasive testing for bladder cancer.

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

    PubMed

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim; Millikan, Randall E; Stadler, Walter; De Mulder, Pieter; Sherif, Amir; von der Maase, Hans; Tsukamoto, Taiji; Soloway, Mark S

    2007-01-01

    To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed, as is chemotherapy for patients with metastatic urothelial cancer. The conference panel consisted of 10 medical oncologists and urologists from 3 continents who are experts in this field and who reviewed the English-language literature through October 2004. Relevant English-language literature was identified with the use of Medline; additional cited works not detected on the initial search regarding neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and chemotherapy for patients with metastatic urothelial cancer were reviewed. Evidence-based recommendations for diagnosis and management of the disease were made with reference to a 4-point scale. Results of the authors' deliberations are presented as a consensus document. Meta-analysis of randomized trials on cisplatin-containing combination neoadjuvant chemotherapy revealed a 5% difference in favor of neoadjuvant chemotherapy. No randomized trials have yet compared survival with transurethral resection of bladder tumor alone versus cystectomy for the management of patients with muscle-invasive disease. Collaborative international adjuvant chemotherapy trials are needed to assist researchers in assessing the true value of adjuvant chemotherapy. Systemic cisplatin-based combination chemotherapy is the only current modality that has been shown in phase 3 trials to improve survival in responsive patients

  2. Chemotherapy and targeted therapy for gall bladder cancer.

    PubMed

    Sirohi, Bhawna; Singh, Ashish; Jagannath, P; Shrikhande, Shailesh V

    2014-06-01

    Gall bladder cancer is a common cancer in the Ganges belt of North-eastern India. In view of incidental diagnosis of gall bladder cancer by physicians and surgeons, the treatment is not optimised. Most patients present in advanced stages and surgery remains the only option to cure. This review highlights the current evidence in advances in systemic therapy of gall bladder cancer.

  3. Glucocorticoid therapy and risk of bladder cancer

    PubMed Central

    Dietrich, K; Schned, A; Fortuny, J; Heaney, J; Marsit, C; Kelsey, K T; Karagas, M R

    2009-01-01

    Background: Use of immunosuppressive drugs post organ transplantation, and prolonged use of glucorticoids for other conditions have been associated with subsequent risk of certain malignancies, that is, skin cancers and lymphoma. There is evidence that the incidence of bladder cancer is also elevated among organ transplant recipients, however, it is unknown whether other groups of patients, that is, those taking oral glucocorticoids, likewise are at an increased risk. Methods: In a population-based case–control study in New Hampshire, USA, we compared the use of glucocorticoids in 786 bladder cancer cases and in 1083 controls. We used unconditional logistic regression analysis to compute adjusted odds ratios (ORs) associated with oral glucocorticoid use. Results: In our analysis, the risk of bladder cancer was related to a history of prolonged oral glucocorticoid use (OR=1.85, 95% CI=1.24–2.76, adjusted for age, gender and smoking). Associations with oral glucocorticoid use were stronger for invasive tumours (OR=2.12, 95% CI=1.17–3.85) and tumours with high (3+) p53 staining intensity (OR=2.35, 95% CI=1.26–4.36). Conclusion: Our results raise the possibility of an increased risk of bladder cancer from systemic use of glucocorticoids, and a potential role of immune surveillance in bladder cancer aetiology. PMID:19773763

  4. Identification and validation of reference genes for the detection of serum microRNAs by reverse transcription-quantitative polymerase chain reaction in patients with bladder cancer.

    PubMed

    Wang, Lishui; Liu, Yimin; Du, Lutao; Li, Juan; Jiang, Xiumei; Zheng, Guixi; Qu, Ailin; Wang, Haiyan; Wang, Lili; Zhang, Xin; Liu, Hui; Pan, Hongwei; Yang, Yongmei; Wang, Chuanxin

    2015-07-01

    Serum microRNAs (miRNAs) have been proposed as novel non-invasive biomarkers for the early detection of cancer. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is the most commonly used method for investigating miRNA expression levels, however, the interpretation of RT-qPCR results depends largely on normalization to an appropriate endogenous control. The present study involved 129 patients with non-muscle-invasive bladder cancer (NMIBC), 121 patients with muscle-invasive bladder cancer (MIBC) and 158 healthy controls. The aim of the present study was to determine the most stable reference genes for the investigations of serum miRNA in bladder cancer (BC). MiSeq sequencing was performed and the expression levels of 10 miRNAs and U6 were then measured using RT-qPCR. Following RT‑qPCR, five genes (hsa-miR-193a-5p, hsa-miR-16-5p, U6, hsa-miR-191-5p and hsa-let-7d-3p) were selected for stability analysis using geNorm and NormFinder software. These algorithms identified hsa-miR-193a-5p and hsa-miR-16-5p as the most stably expressed reference genes. The availability of hsa-miR-193a-5p and hsa-miR-16-5p was confirmed in an additional cohort. One-way analysis of variance indicated that no significant differences were present in the expression levels among the three groups. Furthermore, miR-148b-3p was selected as a target miRNA to determine the effect of hsa-miR-193a-5p and hsa-miR-16-5p on miRNA quantification. The combined use of hsa-miR-193a-5p and hsa-miR-16-5p enabled the detection of a significant upregulation of miR-148b-3p in the BC serum. The results of the present study demonstrated that normalization of miRNA data, using a combination of hsa-miR-193a-5p and hsa-miR-16-5p as reference genes, may produce reliable and accurate results for the detection of serum miRNAs in BC.

  5. Current perspectives in bladder cancer management.

    PubMed

    Griffiths, T R L

    2013-05-01

    More than 350,000 new cases of bladder cancer are diagnosed worldwide each year; the vast majority (> 90%) of these are transitional cell carcinomas (TCC). The most important risk factors for the development of bladder cancer are smoking and occupational exposure to toxic chemicals. Painless visible haematuria is the most common presenting symptom of bladder cancer; significant haematuria requires referral to a specialist urology service. Cystoscopy and urine cytology are currently the recommended tools for diagnosis of bladder cancer. Excluding muscle invasion is an important diagnostic step, as outcomes for patients with muscle invasive TCC are less favourable. For non-muscle invasive bladder cancer, transurethral resection followed by intravesical chemotherapy (typically Mitomycin C or epirubicin) or immunotherapy [bacillus Calmette-Guérin (BCG)] is the current standard of care. For patients failing BCG therapy, cystectomy is recommended; for patients unsuitable for surgery, the choice of treatment options is currently limited. However, novel interventions, such as chemohyperthermia and electromotive drug administration, enhance the effects of conventional chemotherapeutic agents and are being evaluated in Phase III trials. Radical cystectomy (with pelvic lymphadenectomy and urinary diversion) or radical radiotherapy are the current established treatments for muscle invasive TCC. Neoadjuvant chemotherapy is recommended before definitive treatment of muscle invasive TCC; cisplatin-containing combination chemotherapy is the recommended regimen. Palliative chemotherapy is the first-choice treatment in metastatic TCC. © 2012 Blackwell Publishing Ltd.

  6. Bladder cancer: smoking, beverages and artificial sweeteners

    PubMed Central

    Morgan, Robert W.; Jain, Meera G.

    1974-01-01

    A matched patient-control study of bladder cancer examined the relationship of the disease to occupation, smoking and intake of tea, coffee, cola, alcohol and artificial sweeteners. There was no association of disease with occupation for these patients. Heavy smoking gave relative risks of 6.37 and 4.36 for men and women respectively; there was evidence of a dose-response relationship. Tea and coffee intake did not increase the risk of disease nor did prolonged use of artificial sweeteners. Alcohol and cola intake increased the relative risk of bladder cancer among male smokers. There is some suggestion that smoking interacts with both alcohol and cola intake in the production of bladder cancer. PMID:4429932

  7. 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

  8. [Synchronous male bladder cancer and breast cancer - a case report].

    PubMed

    Yabe, Nobushige; Murai, Shinji; Kunugi, Chikara; Nakadai, Jyunpei; Oto, Ippei; Yoshikawa, Takahisa; Kitasato, Kenjiro; Shimizu, Hirotomo; Nakamura, Akihiko; Masuda, Aya; Miyazaki, Yasumasa; Ohashi, Masakazu; Jinno, Hiromitsu; Kitagawa, Yuko

    2014-11-01

    A 74-year-old man complained of blood in his urine over a 1-week period beginning in early October 2013, and was examined in the urology department of our hospital. A thorough examination revealed bladder cancer, and surgery was planned after two cycles of preoperative gemcitabine plus cisplatin chemotherapy. A chest computed tomography (CT) performed to evaluate the response to chemotherapy revealed a mass in the right breast. The patient had previously complained about the same site, and mammography and ultrasonography had suggested the possibility of a malignant mammary gland tumor. The results of aspiration cytology were Class V, and based on that finding, a diagnosis of cancer of the right breast was made. In February 2014, we performed a mastectomy, while preserving the pectoral muscles, along with sentinel node biopsy, total cystectomy, urethrectomy, pelvic lymph node dissection, and ureteroileal anastomosis. The histopathological diagnosis of the right breast tumor was invasive ductal carcinoma[scirrhous carcinoma, ly (+), v (-), g (+), f (+), s (+), nuclear grade 1=atypia 2+mitosis 1, EIC (-), ICT (-), NCAT (-)]. A micrometastatic tumor measuring approximately 1mm was observed in the sentinel lymph node. The breast disease was classified as pT1N1mi(sn)M0, Stage IIA, and the tumor was ER (+), PgR (+), HER2/neu (2+), and FISH (-). The bladder cancer was diagnosed as urothelial carcinoma, non-papillary, invasive G2>G3, pT2a; no pelvic lymph node metastases were detected, and it was classified as pT2aN0M0, Stage II. Synchronous male breast cancer and bladder cancer is a very rare condition, and we report the case with a review of the literature.

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

    ClinicalTrials.gov

    2017-03-30

    Recurrent Bladder 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

  10. Targeting glycogen metabolism in bladder cancer

    PubMed Central

    Lew, Carolyn Ritterson; Guin, Sunny; Theodorescu, Dan

    2015-01-01

    Metabolism has been a heavily investigated topic in cancer research for the past decade. Although the role of aerobic glycolysis (the Warburg effect) in cancer has been extensively studied, abnormalities in other metabolic pathways are only just being understood in cancer. One such pathway is glycogen metabolism; its involvement in cancer development, particularly in urothelial malignancies, and possible ways of exploiting aberrations in this process for treatment are currently being studied. New research shows that the glycogen debranching enzyme amylo-α-1,6-glucosidase, 4-α-glucanotransferase (AGL) is a novel tumour suppressor in bladder cancer. Loss of AGL leads to rapid proliferation of bladder cancer cells. Another enzyme involved in glycogen debranching, glycogen phosphorylase, has been shown to be a tumour promoter in cancer, including in prostate cancer. Studies demonstrate that bladder cancer cells in which AGL expression is lost are more metabolically active than cells with intact AGL expression, and these cells are more sensitive to inhibition of both glycolysis and glycine synthesis—two targetable pathways. As a tumour promoter and enzyme, glycogen phosphorylase can be directly targeted, and preclinical inhibitor studies are promising. However, few of these glycogen phosphorylase inhibitors have been tested for cancer treatment in the clinical setting. Several possible limitations to the targeting of AGL and glycogen phosphorylase might also exist. PMID:26032551

  11. miR-613 inhibits bladder cancer proliferation and migration through targeting SphK1

    PubMed Central

    Yu, Haifeng; Duan, Ping; Zhu, Haibo; Rao, Dapang

    2017-01-01

    Objectives: Increasing evidence has suggested that microRNA (miRNA) dysregulation may contribute to tumor progression and metastasis. However, the role of miR-613 in bladder cancer was still unknown. Materials and methods: qRT-PCR and Western blotting were performed to detect the expression of miR-613 and its direct target gene. CCK-8 analysis, qRT-PCR and cell invasion were performed to measure the cell function. Results: We demonstrated that the expression of miR-613 was downregulated in the bladder cancer cell lines. In addition, miR-613 expression was downregulated in the bladder cancer tissues compared to the adjacent normal tissues. Out of 35 bladder cancer tissues, miR-613 was downregulated in 27 cases compared to the adjacent tissues. Ectopic expression of miR-613 suppressed the bladder cancer cell proliferation and invasion. Moreover, miR-613 overexpression enhanced the expression of epithelial biomarker, Ecadherin, and suppressed the expression of mesenchymal biomarker, Vimentin, Snail and N-cadherin. Furthermore, we identified the Sphingosine kinase 1 (SphK1) as the direct target gene of miR-613 in the bladder cancer cell. Restoration of Sphk1 partially rescued miR-613-inhibited bladder cancer cell proliferation, invasion and EMT. Conclusions: These data suggested that miR-613 acted a tumor suppressive role in bladder cancer through targeting SphK1 in bladder. PMID:28386347

  12. Can we use methylation markers as diagnostic and prognostic indicators for bladder cancer?

    PubMed Central

    Kim, Yong-June

    2016-01-01

    Urothelial carcinomas of the urinary bladder have diverse biological and functional characteristics, and numerous factors are likely to be involved in recurrence, progression, and patient survival. While several molecular markers used to evaluate the development and prognosis of bladder cancer have been studied, they are of limited value; therefore, new molecular parameters useful for predicting the prognosis of bladder cancer patients (particularly patients at high risk of progression and recurrence) are required. Recent progress in the understanding of epigenetic modification and gene silencing has provided new opportunities for the detection, treatment, and prevention of cancer. Methylation is an important molecular mechanism in bladder cancer and may have utility as a prognostic and/or diagnostic marker. This review discusses the epigenetic issues involved in the detection and prediction of bladder cancer. PMID:27326410

  13. An epigenetic biomarker combination of PCDH17 and POU4F2 detects bladder cancer accurately by methylation analyses of urine sediment DNA in Han Chinese

    PubMed Central

    Li, Qiaoling; An, Dan; Fang, Lu; Lin, Youcheng; Hou, Yong; Xu, Abai; Fu, Yu; Lu, Wei; Chen, Xin; Chen, Mingwei; Zhang, Meng; Jiang, Huiling; Zhang, Chuanxia; Dong, Pei; Li, Chong; Chen, Jun; Yang, Guosheng; Liu, Chunxiao; Cai, Zhiming; Zhou, Fangjian; Wu, Song

    2016-01-01

    To develop a routine and effectual procedure of detecting bladder cancer (BlCa), an optimized combination of epigenetic biomarkers that work synergistically with high sensitivity and specificity is necessary. In this study, methylation levels of seven biomarkers (EOMES, GDF15, NID2, PCDH17, POU4F2, TCF21, and ZNF154) in 148 individuals—which including 58 urothelial cell carcinoma (UCC) patients, 20 infected urinary calculi (IUC) patients, 20 kidney cancer (KC) patients,20 prostate cancer (PC) patients, and 30 healthy volunteers (HV)—were quantified by qMSP using the urine sediment DNA. Receiver operating characteristic (ROC) curves were generated for each biomarker. The combining predictors of possible combinations were calculated through logistic regression model. Subsequently, ROC curves of the three best performing combinations were constructed. Then, we validated the three best performing combinations and POU4F2 in another 72 UCC, 21 IUC, 26 KC and 22 PC, and 23 HV urine samples. The combination of POU4F2/PCDH17 has yielded the highest sensitivity and specificity of 90.00% and 93.96% in all the 312 individuals, showing the capability of detecting BlCa effectively among pathologically varied sample groups. PMID:26700620

  14. 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.

  15. New discoveries in the molecular landscape of bladder cancer

    PubMed Central

    Li, Roger; Choi, Woonyoung; Ferguson 3rd, J.E.; Metcalfe, Michael J.; Kamat, Ashish M.

    2016-01-01

    We are currently on the cusp of exponential growth in the understanding of the molecular landscape of bladder cancer. Emerging data regarding the mutational burden and targetable genomic and protein alterations in bladder cancer have allowed us to tap into treatments directed toward specific molecular characteristics of bladder cancer. In parallel, these developments will enable us to better select patients for existing treatments of bladder cancer in a step toward personalized therapy. The present article reviews select discoveries that have advanced our understanding of bladder cancer and gives a glimpse of the exciting opportunities on the not-so-distant horizon. PMID:28105319

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

    PubMed Central

    Ambrose, Sarah R.; Gordon, Naheema S.; Goldsmith, James C.; Wei, Wenbin; Zeegers, Maurice P.; James, Nicholas D.; Knowles, Margaret A.; Bryan, Richard T.; Ward, Douglas G.

    2015-01-01

    Developing a urine test to detect bladder tumours with high sensitivity and specificity is a key goal in bladder cancer research. We hypothesised that bladder cancer-specific glycoproteins might fulfill this role. Lectin-ELISAs were used to study the binding of 25 lectins to 10 bladder cell lines and serum and urine from bladder cancer patients and non-cancer controls. Selected lectins were then used to enrich glycoproteins from the urine of bladder cancer patients and control subjects for analysis by shotgun proteomics. None of the lectins showed a strong preference for bladder cancer cell lines over normal urothlelial cell lines or for urinary glycans from bladder cancer patients over those from non-cancer controls. However, several lectins showed a strong preference for bladder cell line glycans over serum glycans and are potentially useful for enriching glycoproteins originating from the urothelium in urine. Aleuria alantia lectin affinity chromatography and shotgun proteomics identified mucin-1 and golgi apparatus protein 1 as proteins warranting further investigation as urinary biomarkers for low-grade bladder cancer. Glycosylation changes in bladder cancer are not reliably detected by measuring lectin binding to unfractionated proteomes, but it is possible that more specific reagents and/or a focus on individual proteins may produce clinically useful biomarkers. PMID:28248271

  17. New Optical Imaging Technologies for Bladder Cancer: Considerations and Perspectives

    PubMed Central

    Liu, Jen-Jane; Droller, Michael J.; Liao, Joseph C.

    2014-01-01

    Purpose Bladder cancer presents as a spectrum of different diatheses. Accurate assessment for individualized treatment depends on initial diagnostic accuracy. Detection relies on white light cystoscopy accuracy and comprehensiveness. Aside from invasiveness and potential risks, white light cystoscopy shortcomings include difficult flat lesion detection, precise tumor delineation to enable complete resection, inflammation and malignancy differentiation, and grade and stage determination. Each shortcoming depends on surgeon ability and experience with the technology available for visualization and resection. Fluorescence cystoscopy/photodynamic diagnosis, narrow band imaging, confocal laser endomicroscopy and optical coherence tomography address the limitations and have in vivo feasibility. They detect suspicious lesions (photodynamic diagnosis and narrow band imaging) and further characterize lesions (optical coherence tomography and confocal laser endomicroscopy). We analyzed the added value of each technology beyond white light cystoscopy and evaluated their maturity to alter the cancer course. Materials and Methods Detailed PubMed® searches were done using the terms “fluorescence cystoscopy,” “photodynamic diagnosis,” “narrow band imaging,” “optical coherence tomography” and “confocal laser endomicroscopy” with “optical imaging,” “bladder cancer” and “urothelial carcinoma.” Diagnostic accuracy reports and all prospective studies were selected for analysis. We explored technological principles, preclinical and clinical evidence supporting nonmuscle invasive bladder cancer detection and characterization, and whether improved sensitivity vs specificity translates into improved correlation of diagnostic accuracy with recurrence and progression. Emerging preclinical technologies with potential application were reviewed. Results Photodynamic diagnosis and narrow band imaging improve nonmuscle invasive bladder cancer detection, including

  18. Bladder cancer diagnosis and identification of clinically significant disease by combined urinary detection of Mcm5 and nuclear matrix protein 22.

    PubMed

    Kelly, John D; Dudderidge, Tim J; Wollenschlaeger, Alex; Okoturo, Odu; Burling, Keith; Tulloch, Fiona; Halsall, Ian; Prevost, Teresa; Prevost, Andrew Toby; Vasconcelos, Joana C; Robson, Wendy; Leung, Hing Y; Vasdev, Nikhil; Pickard, Robert S; Williams, Gareth H; Stoeber, Kai

    2012-01-01

    Urinary biomarkers for bladder cancer detection are constrained by inadequate sensitivity or specificity. Here we evaluate the diagnostic accuracy of Mcm5, a novel cell cycle biomarker of aberrant growth, alone and in combination with NMP22. 1677 consecutive patients under investigation for urinary tract malignancy were recruited to a prospective blinded observational study. All patients underwent ultrasound, intravenous urography, cystoscopy, urine culture and cytologic analysis. An immunofluorometric assay was used to measure Mcm5 levels in urine cell sediments. NMP22 urinary levels were determined with the FDA-approved NMP22® Test Kit. Genito-urinary tract cancers were identified in 210/1564 (13%) patients with an Mcm5 result and in 195/1396 (14%) patients with an NMP22 result. At the assay cut-point where sensitivity and specificity were equal, the Mcm5 test detected primary and recurrent bladder cancers with 69% sensitivity (95% confidence interval = 62-75%) and 93% negative predictive value (95% CI = 92-95%). The area under the receiver operating characteristic curve for Mcm5 was 0.75 (95% CI = 0.71-0.79) and 0.72 (95% CI = 0.67-0.77) for NMP22. Importantly, Mcm5 combined with NMP22 identified 95% (79/83; 95% CI = 88-99%) of potentially life threatening diagnoses (i.e. grade 3 or carcinoma in situ or stage ≥pT1) with high specificity (72%, 95% CI = 69-74%). The Mcm5 immunoassay is a non-invasive test for identifying patients with urothelial cancers with similar accuracy to the FDA-approved NMP22 ELISA Test Kit. The combination of Mcm5 plus NMP22 improves the detection of UCC and identifies 95% of clinically significant disease. Trials of a commercially developed Mcm5 assay suitable for an end-user laboratory alongside NMP22 are required to assess their potential clinical utility in improving diagnostic and surveillance care pathways.

  19. Bladder cancer: molecular determinants of personalized therapy.

    PubMed

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

    2015-01-01

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

  20. Arsenic and bladder cancer: observations and suggestions.

    PubMed

    Radosavljević, Vladan; Jakovljević, Branko

    2008-10-01

    Arsenic from drinking water is a well-known risk factor for bladder cancer. The purpose of this paper is to systematize some important yet often overlooked facts considering the relationship between arsenic exposure and the occurrence of bladder cancer. Since the exposure to inorganic arsenic from food, inhaled air, and skin absorption as well as arsenic methylation ability are not fully investigated, our assumption is that the exposure of arsenic only from drinking water is underestimated and its role as a risk factor is highly overestimated. This paper proposes some qualitative and quantitative parameters of arsenic as a risk factor for bladder cancer. The recommended qualitative parameters of arsenic intake are first, pathways of exposure, and second, toxicity and metabolism. The suggested quantitative parameters of arsenic intake include amounts of arsenic absorbed in the body, duration of arsenic exposure, and duration of arsenic presence in the urinary bladder. This approach can be implemented in a systematic classification and explanation of various risk factors and their mutual interactions for other types of cancer or diseases in general.

  1. Metabolomic profiling reveals potential markers and bioprocesses altered in bladder cancer progression.

    PubMed

    Putluri, Nagireddy; Shojaie, Ali; Vasu, Vihas T; Vareed, Shaiju K; Nalluri, Srilatha; Putluri, Vasanta; Thangjam, Gagan Singh; Panzitt, Katrin; Tallman, Christopher T; Butler, Charles; Sana, Theodore R; Fischer, Steven M; Sica, Gabriel; Brat, Daniel J; Shi, Huidong; Palapattu, Ganesh S; Lotan, Yair; Weizer, Alon Z; Terris, Martha K; Shariat, Shahrokh F; Michailidis, George; Sreekumar, Arun

    2011-12-15

    Although alterations in xenobiotic metabolism are considered causal in the development of bladder cancer, the precise mechanisms involved are poorly understood. In this study, we used high-throughput mass spectrometry to measure over 2,000 compounds in 58 clinical specimens, identifying 35 metabolites which exhibited significant changes in bladder cancer. This metabolic signature distinguished both normal and benign bladder from bladder cancer. Exploratory analyses of this metabolomic signature in urine showed promise in distinguishing bladder cancer from controls and also nonmuscle from muscle-invasive bladder cancer. Subsequent enrichment-based bioprocess mapping revealed alterations in phase I/II metabolism and suggested a possible role for DNA methylation in perturbing xenobiotic metabolism in bladder cancer. In particular, we validated tumor-associated hypermethylation in the cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) promoters of bladder cancer tissues by bisulfite sequence analysis and methylation-specific PCR and also by in vitro treatment of T-24 bladder cancer cell line with the DNA demethylating agent 5-aza-2'-deoxycytidine. Furthermore, we showed that expression of CYP1A1 and CYP1B1 was reduced significantly in an independent cohort of bladder cancer specimens compared with matched benign adjacent tissues. In summary, our findings identified candidate diagnostic and prognostic markers and highlighted mechanisms associated with the silencing of xenobiotic metabolism. The metabolomic signature we describe offers potential as a urinary biomarker for early detection and staging of bladder cancer, highlighting the utility of evaluating metabolomic profiles of cancer to gain insights into bioprocesses perturbed during tumor development and progression.

  2. Prognostic significance of selected lifestyle factors in urinary bladder cancer.

    PubMed

    Wakai, K; Ohno, Y; Obata, K; Aoki, K

    1993-12-01

    To examine the prognostic significance of lifestyle factors in urinary bladder cancer, we conducted a follow-up study of 258 incident bladder cancer patients, who were originally recruited in a case-control study in metropolitan Nagoya. Information on individual survivals was obtained from the computer data-file of the tumor registry of the Nagoya Bladder Cancer Research Group. Univariate analyses revealed significant associations of 5-year survivorship with educational attainment, marital status, drinking habits and consumption of green tea in males, and age at first consultation, histological type and grade of tumor, stage and distant metastasis in both sexes. After adjustment for age, stage, histology (histological type and grade) and distant metastasis by means of a proportional hazards model, drinking of alcoholic beverages was significantly associated with the prognosis of bladder cancer in males. Its adjusted hazard ratio was 0.46 (95% confidence interval: 0.26-0.79), favoring patients who had taken alcoholic beverages. In detailed analysis, ex-drinkers and all levels of current drinkers demonstrated hazard ratios smaller than unity, although no clear dose-response relationship was detected. No prognostic significance was found for such lifestyle factors as smoking habit, uses of artificial sweeteners and hairdye, and consumption of coffee, black tea, matcha (powdered green tea) and cola.

  3. Bladder cancer in Spain 2011: population based study.

    PubMed

    Miñana, B; Cózar, J M; Palou, J; Unda Urzaiz, M; Medina-Lopez, R A; Subirá Ríos, Jorge; de la Rosa-Kehrmann, F; Chantada-Abal, V; Lozano, F; Ribal, Maria J; Rodríguez Fernández, E; Castiñeiras Fernández, J; Concepción Masip, Tomás; Requena-Tapia, M J; Moreno-Sierra, J; Hevia, M; Gómez Rodríguez, A; Martínez-Ballesteros, C; Ramos, M; Amón Sesmero, José H; Pizá Reus, P; Bohorquez Barrientos, A; Rioja Sanz, Carlos; Gomez-Pascual, J Angel; Hidalgo Zabala, E; Parra Escobar, J L; Serrano, O

    2014-02-01

    We estimate the annual incidence of bladder cancer in Spain and describe the clinical profile of patients with bladder cancer enrolled in a population based study. Using the structure of the Spanish National Health System as a basis, in 2011 the AEU (Spanish Association of Urology) conducted this study with a representative sample from 26 public hospitals and a reference population of 10,146,534 inhabitants, comprising 21.5% of the Spanish population. A total of 4,285 episodes of bladder cancer were diagnosed, of which 2,476 (57.8%) were new cases and 1,809 (42.2%) were cases of recurrence, representing an estimated 11,539 new diagnoses annually in Spain. The incidence of bladder cancer in Spain, age adjusted to the standard European population, was 20.08 cases per 100,000 inhabitants (95% CI 13.9, 26.3). Of patients diagnosed with a first episode of bladder cancer 84.3% were male, generally older than 59 years (81.7%) with a mean ± SD age of 70.5 ± 11.4 years. Of these patients 87.5% presented with some type of clinical symptom, with macroscopic hematuria (90.8%) being the most commonly detected. The majority of primary tumors were nonmuscle invasive (76.7%) but included a high proportion of high grade tumors (43.7%). According to the ISUP (International Society of Urologic Pathology)/WHO (2004) classification 51.1% was papillary high grade carcinoma. Carcinoma in situ was found in 2.2% of primary and 5.8% of recurrent cases. The incidence of bladder cancer in Spain, age adjusted to the standard European population, confirms that Spain has one of the highest incidences in Europe. Most primary nonmuscle invasive bladder cancer corresponded to high risk patients but with a low detected incidence of carcinoma in situ. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  4. Probiotics, dendritic cells and bladder cancer.

    PubMed

    Feyisetan, Oladapo; Tracey, Christopher; Hellawell, Giles O

    2012-06-01

    What's known on the subject? and What does the study add? The suppressor effect of probiotics on superficial bladder cancer is an observed phenomenon but the specific mechanism is poorly understood. The evidence strongly suggests natural killer (NK) cells are the anti-tumour effector cells involved and NK cell activity correlates with the observed anti-tumour effect in mice. It is also known that dendritic cells (DC) cells are responsible for the recruitment and mobilization of NK cells so therefore it may be inferred that DC cells are most likely to be the interphase point at which probiotics act. In support of this, purification of NK cells was associated with a decrease in NK cells activity. The current use of intravesical bacille Calmette-Guérin in the management of superficial bladder cancer is based on the effect of a localised immune response. In the same way, understanding the mechanism of action of probiotics and the role of DC may potentially offer another avenue via which the immune system may be manipulated to resist bladder cancer. Probiotic foods have been available in the UK since 1996 with the arrival of the fermented milk drink (Yakult) from Japan. The presence of live bacterial ingredients (usually lactobacilli species) may confer health benefits when present in sufficient numbers. The role of probiotics in colo-rectal cancer may be related in part to the suppression of harmful colonic bacteria but other immune mechanisms are involved. Anti-cancer effects outside the colon were suggested by a Japanese report of altered rates of bladder tumour recurrence after ingestion of a particular probiotic. Dendritic cells play a central role to the general regulation of the immune response that may be modified by probiotics. The addition of probiotics to the diet may confer benefit by altering rates of bladder tumour recurrence and also alter the response to immune mechanisms involved with the application of intravesical treatments (bacille Calmette-Guérin).

  5. Metabolic alterations in bladder cancer: applications for cancer imaging.

    PubMed

    Whyard, Terry; Waltzer, Wayne C; Waltzer, Douglas; Romanov, Victor

    2016-02-01

    Treatment planning, outcome and prognosis are strongly related to the adequate tumor staging for bladder cancer (BC). Unfortunately, a large discrepancy exists between the preoperative clinical and final pathologic staging. Therefore, an advanced imaging-based technique is crucial for adequate staging. Although Magnetic Resonance Imaging (MRI) is currently the best in vivo imaging technique for BC staging because of its excellent soft-tissue contrast and absence of ionizing radiation it lacks cancer-specificity. Tumor-specific positron emission tomography (PET), which is based on the Warburg effect (preferential uptake of glucose by cancer cells), exploits the radioactively-labeled glucose analogs, i.e., FDG. Although FDG-PET is highly cancer specific, it lacks resolution and contrast quality comparable with MRI. Chemical Exchange Saturation Transfer (CEST) MRI enables the detection of low concentrations of metabolites containing protons. BC is an attractive target for glucose CEST MRI because, in addition to the typical systemic administration, glucose might also be directly applied into the bladder to reduce toxicity-related complications. As a first stage of the development of a contrast-specific BC imaging technique we have studied glucose uptake by bladder epithelial cells and have observed that glucose is, indeed, consumed by BC cells with higher intensity than by non-transformed urothelial cells. This effect might be partly explained by increased expression of glucose transporters GLUT1 and GLUT3 in transformed cells as compared to normal urothelium. We also detected higher lactate production by BC cells which is another cancer-specific manifestation of the Warburg effect. In addition, we have observed other metabolic alterations in BC cells as compared to non-transformed cells: in particular, increased pyruvate synthesis. When glucose was substituted by glutamine in culture media, preferential uptake of glutamine by BC cells was observed. The preferential

  6. Bladder cancer: approaches to prevention and control*

    PubMed Central

    Koroltchouk, V.; Stanley, K.; Stjernswärd, J.; Mott, K.

    1987-01-01

    Bladder cancer is the twelfth most common cancer globally, with approximately 170 000 new cases each year; a third of these cases are in the developing countries. There are two major etiological types. The first is more common in the industrialized countries and is associated with exposure to certain occupational and environmental carcinogens, but most importantly with tobacco smoking. The second type is associated with Schistosoma haematobium infection of the urinary tract and is one of the most frequent tumours in eastern Mediterranean and African countries. Both types of bladder cancer are largely preventable. Comprehensive education and legislative approaches are recommended to reduce tobacco consumption and exposure to industrial carcinogens. Safe and effective drugs are available to treat schistosomiasis within integrated control programmes in endemic areas. PMID:3121200

  7. Neoadjuvant Intravesical Vaccine Therapy in Treating Patients With Bladder Carcinoma Who Are Undergoing Cystectomy

    ClinicalTrials.gov

    2014-12-22

    Bladder Adenocarcinoma; Bladder Squamous Cell Carcinoma; Bladder Urothelial Carcinoma; Recurrent Bladder Carcinoma; Stage I Bladder Cancer; Stage II Bladder Cancer; Stage III Bladder Cancer; Stage IV Bladder Cancer

  8. Differentially expressed genes in metastatic advanced Egyptian bladder cancer.

    PubMed

    Zekri, Abdel-Rahman N; Hassan, Zeinab Korany; Bahnassy, Abeer A; Khaled, Hussein M; El-Rouby, Mahmoud N; Haggag, Rasha M; Abu-Taleb, Fouad M

    2015-01-01

    Bladder cancer is one of the most common cancers worldwide. Gene expression profiling using microarray technologies improves the understanding of cancer biology. The aim of this study was to determine the gene expression profile in Egyptian bladder cancer patients. Samples from 29 human bladder cancers and adjacent non-neoplastic tissues were analyzed by cDNA microarray, with hierarchical clustering and multidimensional analysis. Five hundred and sixteen genes were differentially expressed of which SOS1, HDAC2, PLXNC1, GTSE1, ULK2, IRS2, ABCA12, TOP3A, HES1, and SRP68 genes were involved in 33 different pathways. The most frequently detected genes were: SOS1 in 20 different pathways; HDAC2 in 5 different pathways; IRS2 in 3 different pathways. There were 388 down-regulated genes. PLCB2 was involved in 11 different pathways, MDM2 in 9 pathways, FZD4 in 5 pathways, p15 and FGF12 in 4 pathways, POLE2 in 3 pathways, and MCM4 and POLR2E in 2 pathways. Thirty genes showed significant differences between transitional cell cancer (TCC) and squamous cell cancer (SCC) samples. Unsupervised cluster analysis of DNA microarray data revealed a clear distinction between low and high grade tumors. In addition 26 genes showed significant differences between low and high tumor stages, including fragile histidine triad, Ras and sialyltransferase 8 (alpha) and 16 showed significant differences between low and high tumor grades, like methionine adenosyl transferase II, beta. The present study identified some genes, that can be used as molecular biomarkers or target genes in Egyptian bladder cancer patients.

  9. Electrochemical immunosensor for detecting typical bladder cancer biomarker based on reduced graphene oxide-tetraethylene pentamine and trimetallic AuPdPt nanoparticles.

    PubMed

    Ma, Hongmin; Zhang, Xiaoyue; Li, Xiaojian; Li, Rongxia; Du, Bin; Wei, Qin

    2015-10-01

    A highly sensitive electrochemical immunosensor for detection of typical bladder cancer biomarker-nuclear matrix protein 22 (NMP22) was developed by using reduced graphene oxide-tetraethylene pentamine (rGO-TEPA) and trimetallic AuPdPt nanoparticles (NPs). rGO-TEPA was used as the ideal material for signal amplification and AuPdPt NPs immobilization due to its excellent conductivity and large surface area. An effective platform was constructed for antibodies anchoring by using AuPdPt NPs, which kept the antibodies' high stability and bioactivity. Moreover, AuPdPt NPs could accelerate the electron transfer and enhance the signal response, which assisted by the synergistic effect of the three different metals (Au, Pd and Pt). The proposed immunosensor showed satisfied performance such as simple fabrication, low detection limits (0.01 U/mL), wide linear range (from 0.040 to 20 U/mL), short analysis time (2 min), high stability and selectivity in the detection of NMP22. Furthermore, the proposed immunosensor was employed to test real urine samples with satisfactory results.

  10. Intravesical Treatments of Bladder Cancer: Review

    PubMed Central

    Shen, Zancong; Shen, Tong; Wientjes, M. Guillaume; O’Donnell, Michael A.

    2008-01-01

    For bladder cancer, intravesical chemo/immunotherapy is widely used as adjuvant therapies after surgical transurethal resection, while systemic therapy is typically reserved for higher stage, muscle-invading, or metastatic diseases. The goal of intravesical therapy is to eradicate existing or residual tumors through direct cytoablation or immunostimulation. The unique properties of the urinary bladder render it a fertile ground for evaluating additional novel experimental approaches to regional therapy, including iontophoresis/electrophoresis, local hyperthermia, co-administration of permeation enhancers, bioadhesive carriers, magnetic-targeted particles and gene therapy. Furthermore, due to its unique anatomical properties, the drug concentration-time profiles in various layers of bladder tissues during and after intravesical therapy can be described by mathematical models comprised of drug disposition and transport kinetic parameters. The drug delivery data, in turn, can be combined with the effective drug exposure to infer treatment efficacy and thereby assists the selection of optimal regimens. To our knowledge, intravesical therapy of bladder cancer represents the first example where computational pharmacological approach was used to design, and successfully predicted the outcome of, a randomized phase III trial (using mitomycin C). This review summarizes the pharmacological principles and the current status of intravesical therapy, and the application of computation to optimize the drug delivery to target sites and the treatment efficacy. PMID:18369709

  11. Bladder Cancer: A Simple Model Becomes Complex

    PubMed Central

    Pierro, Giovanni Battista Di; Gulia, Caterina; Cristini, Cristiano; Fraietta, Giorgio; Marini, Lorenzo; Grande, Pietro; Gentile, Vincenzo; Piergentili, Roberto

    2012-01-01

    Bladder cancer is one of the most frequent malignancies in developed countries and it is also characterized by a high number of recurrences. Despite this, several authors in the past reported that only two altered molecular pathways may genetically explain all cases of bladder cancer: one involving the FGFR3 gene, and the other involving the TP53 gene. Mutations in any of these two genes are usually predictive of the malignancy final outcome. This cancer may also be further classified as low-grade tumors, which is always papillary and in most cases superficial, and high-grade tumors, not necessarily papillary and often invasive. This simple way of considering this pathology has strongly changed in the last few years, with the development of genome-wide studies on expression profiling and the discovery of small non-coding RNA affecting gene expression. An easy search in the OMIM (On-line Mendelian Inheritance in Man) database using “bladder cancer” as a query reveals that genes in some way connected to this pathology are approximately 150, and some authors report that altered gene expression (up- or down-regulation) in this disease may involve up to 500 coding sequences for low-grade tumors and up to 2300 for high-grade tumors. In many clinical cases, mutations inside the coding sequences of the above mentioned two genes were not found, but their expression changed; this indicates that also epigenetic modifications may play an important role in its development. Indeed, several reports were published about genome-wide methylation in these neoplastic tissues, and an increasing number of small non-coding RNA are either up- or down-regulated in bladder cancer, indicating that impaired gene expression may also pass through these metabolic pathways. Taken together, these data reveal that bladder cancer is far to be considered a simple model of malignancy. In the present review, we summarize recent progress in the genome-wide analysis of bladder cancer, and analyse non

  12. Cytochrome P4501A2 Phenotype and Bladder Cancer Risk: The Shanghai Bladder Cancer Study

    PubMed Central

    Tao, Li; Xiang, Yong-Bing; Chan, Kenneth K.; Wang, Renwei; Gao, Yu-Tang; Yu, Mimi C.; Yuan, Jian-Min

    2011-01-01

    Cytochrome P450 1A2 (CYP1A2) is hypothesized to catalyze the activation of arylamines, known human bladder carcinogens present in cigarette smoke. The relationship between CYP1A2 phenotype and bladder cancer risk was examined in a case-control study involving 519 patients and 514 controls in Shanghai, China. Both CYP1A2 and N-acetyltransferase 2 (NAT2) phenotypic status were determined by a caffeine-based urinary assay. The present study showed that among smokers at urine collection, bladder cancer patients had statistically significantly higher CYP1A2 phenotype scores compared with control subjects (P = 0.001). The odds ratios (95% confidence intervals) of bladder cancer for the 2nd, 3rd, and 4th quartiles of the CYP1A2 score were 1.31 (0.53–3.28), 2.04 (0.90–4.60) and 2.82 (1.32–6.05), respectively, relative to the lowest quartile (P for trend = 0.003). NAT2 slow acetylation phenotype was associated with a statistically significant 40% increased risk of bladder cancer, and the relationship was independent of subjects’ smoking status. Subjects possessing the NAT2 slow acetylation phenotype and the highest tertile of CYP1A2 scores showed the highest risk for bladder cancer. Their odds ratios (95% confidence intervals) was 2.13 (1.24–3.68) relative to their counterparts possessing the NAT2 rapid acetylation phenotype and the lowest tertile of CYP1A2 scores. The findings of the present study demonstrate that CYP1A2 phenotype may be an important contributing factor in the development of smoking-related bladder cancer in humans. PMID:21480221

  13. Neoadjuvant chemotherapy for invasive bladder cancer.

    PubMed

    Sonpavde, Guru; Sternberg, Cora N

    2012-04-01

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

  14. [Management of bladder cancer in unfit patients].

    PubMed

    Mongiat-Artus, P; Pfister, C; Théodore, C; De Crevoisier, R; Guillotreau, J

    2010-03-01

    Adjuvant therapies in bladder cancer are based on risk of recurrence and associated comorbidities (renal failure). Lymph node involvement is the most important prognostic factor for decision. Two adjuvant chemotherapies exist: MVAC or GC. In unfit patients, association (Gemcitabine and Taxanes) could be proposed. Indication of adjuvant radiotherapy depends on metastatic risk and resection margins. Concomitant chemotherapy and radiotherapy should be proposed to selected patients who refuse or are not candidate for radical cystectomy.

  15. FGFR3 and Cyclin D3 as urine biomarkers of bladder cancer recurrence.

    PubMed

    Blanca, Ana; Requena, Maria J; Alvarez, Jose; Cheng, Liang; Montironi, Rodolfo; Raspollini, Maria R; Reymundo, Carlos; Lopez-Beltran, Antonio

    2016-01-01

    To assess the diagnostic performance of FGFR3 and Cyclin D3 urinary protein levels in detecting bladder cancer recurrence. Urine of 321 patients in follow-up for bladder cancer and 150 non-neoplastic urine controls was included. Cytology, cystoscopy and FGFR3 and Cyclin D3 expression by western blot were performed. One hundred ten (34.3%) patients had evidence of tumor recurrence. The sensitivity and specificity of cytology/cystoscopy was 80 and 84%, and for FGFR3/Cyclin D3 was of 73 and 90%. Combined urinary FGFR3/Cyclin D3 expression shows improved detection rates for bladder cancer recurrence with high specificity and sensitivity, and within the same range of detection shown by cystoscopy, therefore supporting its potential use as noninvasive diagnostic biomarker for bladder cancer recurrence.

  16. 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

  17. 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.

  18. Nursing care and treatment of patients with bladder cancer.

    PubMed

    Turner, B

    Bladder cancer is the second most common urological cancer after prostate cancer in the UK. This article aims to update nurses knowledge about the disease, focusing on diagnosis, treatment and nursing care.

  19. Podoplanin serum and urine concentration in transitional bladder cancer.

    PubMed

    Sankiewicz, Anna; Guszcz, Tomasz; Mena-Hortelano, Rocio; Zukowski, Krzysztof; Gorodkiewicz, Ewa

    2016-01-01

    Podoplanin (PDP) is a mucin - a type of transmembrane protein expressed in numerous tissues during ontogeny and in adult animals, including the brain, heart, kidney, osteoblasts and lymphoid organs. The aim of this study was to determine podoplanin concentration in the blood serum and urine of patients with bladder cancer. Quantifying podoplanin concentration and its correlation with various clinicopathological parameters may be useful for more accurate predictions and identifying high-risk patients. The present study included 82 patients with bladder cancer confirmed by transurethral resection or cystectomy and 27 healthy volunteers. The Surface Plasmon Resonance Imaging biosensor was applied for the detection of podoplanin in the serum and urine samples. Significant differences in serum and urine podoplanin concentration levels were observed between bladder cancer patients. The statistically significant higher values of PDP were detected in serum of patients with invasive, more aggressive, larger, multifocal tumors. The association between podoplanin concentration and clinicopathological features indicates that it might be useful while making therapeutic decisions.

  20. 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.

  1. Human bladder cancer diagnosis using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Mukherjee, Sushmita; Wysock, James S.; Ng, Casey K.; Akhtar, Mohammed; Perner, Sven; Lee, Ming-Ming; Rubin, Mark A.; Maxfield, Frederick R.; Webb, Watt W.; Scherr, Douglas S.

    2009-02-01

    At the time of diagnosis, approximately 75% of bladder cancers are non-muscle invasive. Appropriate diagnosis and surgical resection at this stage improves prognosis dramatically. However, these lesions, being small and/or flat, are often missed by conventional white-light cystoscopes. Furthermore, it is difficult to assess the surgical margin for negativity using conventional cystoscopes. Resultantly, the recurrence rates in patients with early bladder cancer are very high. This is currently addressed by repeat cystoscopies and biopsies, which can last throughout the life of a patient, increasing cost and patient morbidity. Multiphoton endoscopes offer a potential solution, allowing real time, noninvasive biopsies of the human bladder, as well as an up-close assessment of the resection margin. While miniaturization of the Multiphoton microscope into an endoscopic format is currently in progress, we present results here indicating that Multiphoton imaging (using a bench-top Multiphoton microscope) can indeed identify cancers in fresh, unfixed human bladder biopsies. Multiphoton images are acquired in two channels: (1) broadband autofluorescence from cells, and (2) second harmonic generation (SHG), mostly by tissue collagen. These images are then compared with gold standard hematoxylin/eosin (H&E) stained histopathology slides from the same specimen. Based on a "training set" and a very small "blinded set" of samples, we have found excellent correlation between the Multiphoton and histopathological diagnoses. A larger blinded analysis by two independent uropathologists is currently in progress. We expect that the conclusion of this phase will provide us with diagnostic accuracy estimates, as well as the degree of inter-observer heterogeneity.

  2. Intervention of nicotine on MNU-induced bladder cancer in rats.

    PubMed

    Liu, Di; Pan, Feng; Li, Bing; Han, Xiaomin; Li, Wencheng; Shi, Ying; Pang, Zili; Zhang, Qijun

    2011-02-01

    This study examined the effect of nicotine on the expression of mutant p53 (mt-p53) in bladder cancer rats. The rat models of bladder cancer were established by infusing N-methyl-nitroso-urea (MNU, 10 mg/kg every 2 weeks for 8 weeks) into the bladder. Pathological examination on the bladder was conducted to confirm the establishment of the model. All the bladder cancer rats were randomly divided into an MNU group and 3 nicotine groups. In the nicotine groups, the rats were intragastrically administered nicotine at different concentrations (25, 15, 5 mg/kg respectively) 3 times per week for 8 weeks. The mt-p53 expression was detected by the immunohistochemical method. The results showed that rat bladder cancer models developed histopathological changes of bladder transitional cell carcinoma. The positive rate of mt-p53 expression in the 3 nicotine groups (25, 15, 5 mg/kg) was 75.00%, 58.33% and 41.67% by the 14th week, respectively, significantly higher than that in the MNU group (33.33%) (all P<0.05). The mt-p53 expression rate was positively correlated with the medication dose and time (P<0.05). It is concluded that nicotine may play an important role in the development of bladder cancer partially by increasing the expression of mt-p53.

  3. Preoperative irradiation and cystectomy for bladder cancer.

    PubMed

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

    1982-03-01

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

  4. [Radical treatment of invasive bladder cancer].

    PubMed

    Lopatkin, N A; Darenkov, S P; Chernyshev, N V; Sokolov, A E; Gorilovskiĭ, M L; Akmatov, N A; Samsonov, Iu V

    2003-01-01

    We have conducted a retrospective analysis of radical cystectomy in 53 patients (45 males and 8 females, 85 and 15%, respectively) with invasive bladder cancer (BC) treated in the Research Institute of Urology in 1997-2002. Stages T2N0M0, pT3aN0M0, T3bN0M0, pT4aN0M0, pT4aN1-2M0 were in 4 (7.5%), 13 (25%), 21 (40%), 7 (12.5%), 8 (15%) cases, respectively. Well differentiated transitional cell BC (G1) was detected in 1 (2%) patient, moderately differentiated (G2) in 16 (30%) cases, poorly differentiated (G3) in 36 (68%) patients. The following methods of urine derivation were used: orthotopic plastic surgery (n = 3, 6%), ureterocutaneostomy (n = 4, 8%), Mainz pouch II operation (n = 16, 30%), Hassan operation (n = 5, 9%), Bricker procedure (n = 22, 44%), transureteroanastomosis (n = 3, 6%). In the postoperative period there was one lethal outcome, early complications in 5 (9%) patients, late complications in 9 (17%) patients. Distant metastases to the lungs, bones and iliac lymph nodes after treatment were detected in 3, 2 and 3 patients, respectively. One patient had a local pelvic recurrence. For 53 patients 2-year corrected survival was 68 +/- 12.0%. We have come to the conclusion that the only radical surgical treatment of invasive BC is cystectomy, limitations to which are connected only with complexity of subsequent urine derivation.

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

    ClinicalTrials.gov

    2017-06-02

    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

  6. 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.

  7. Long noncoding RNA in prostate, bladder, and kidney cancer.

    PubMed

    Martens-Uzunova, Elena S; Böttcher, René; Croce, Carlo M; Jenster, Guido; Visakorpi, Tapio; Calin, George A

    2014-06-01

    Genomic regions without protein-coding potential give rise to millions of protein-noncoding RNA transcripts (noncoding RNA) that participate in virtually all cellular processes. Research over the last 10 yr has accumulated evidence that long noncoding RNAs (lncRNAs) are often altered in human urologic cancers. To review current progress in the biology and implication of lncRNAs associated with prostate, bladder, and kidney cancer. The PubMed database was searched for articles in the English language with combinations of the Medical Subject Headings terms long non coding RNA, long noncoding RNA, long untranslated RNA, cancer, neoplasms, prostate, bladder, and kidney. We summarise existing knowledge on the systematics, biology, and function of lncRNAs, particularly these involved in prostate, kidney, and bladder cancer. We also discuss the possible utilisation of lncRNAs as novel biomarkers and potential therapeutic targets in urologic malignancies and portray the major challenges and future perspectives of ongoing lncRNA research. LncRNAs are important regulators of gene expression interacting with the major pathways of cell growth, proliferation, differentiation, and survival. Alterations in the function of lncRNAs promote tumour formation, progression, and metastasis of prostate, bladder, and kidney cancer. LncRNAs can be used as noninvasive tumour markers in urologic malignancies. Increased knowledge of the molecular mechanisms by which lncRNAs perform their function in the normal and malignant cell will lead to a better understanding of tumour biology and could provide novel therapeutic targets for the treatment of urologic cancers. In this paper we reviewed current knowledge of long noncoding RNAs (lncRNAs) for the detection and treatment of urologic cancers. We conclude that lncRNAs can be used as novel biomarkers in prostate, kidney, or bladder cancer. LncRNAs hold promise as future therapeutic targets, but more research is needed to gain a better

  8. Oncolytic Viruses in the Treatment of Bladder Cancer

    PubMed Central

    Potts, Kyle G.; Hitt, Mary M.; Moore, Ronald B.

    2012-01-01

    Bladder carcinoma is the second most common malignancy of the urinary tract. Up to 85% of patients with bladder cancer are diagnosed with a tumor that is limited to the bladder mucosa (Ta, T1, and CIS). These stages are commonly termed as non-muscle-invasive bladder cancer (NMIBC). Although the treatment of NMIBC has greatly improved in recent years, there is a need for additional therapies when patients fail bacillus Calmette-Guérin (BCG) and chemotherapeutic agents. We propose that bladder cancer may be an ideal target for oncolytic viruses engineered to selectively replicate in and lyse tumor cells leaving normal cells unharmed. In support of this hypothesis, here we review current treatment strategies for bladder cancer and their shortcomings, as well as recent advancements in oncolytic viral therapy demonstrating encouraging safety profiles and antitumor activity. PMID:22899907

  9. Reprogramming bladder cancer cells for studying cancer initiation and progression.

    PubMed

    Iskender, Banu; Izgi, Kenan; Canatan, Halit

    2016-10-01

    The induced pluripotent stem cell (iPSC) technology is the forced expression of specific transcription factors in somatic cells resulting in transformation into self-renewing, pluripotent cells which possess the ability to differentiate into any type of cells in the human body. While malignant cells could also be reprogrammed into iPSC-like cells with lower efficiency due to the genetic and epigenetic barriers in cancer cells, only a limited number of cancer cell types could be successfully reprogrammed until today. In the present study, we aimed at reprogramming two bladder cancer cell lines HTB-9 and T24 using a non-integrating Sendai virus (SeV) system. We have generated six sub-clones using distinct combinations of four factors-OCT4, SOX2, KLF4 and c-MYC-in two bladder cancer cell lines. Only a single sub-clone, T24 transduced with 4Fs, gave rise to iPSC-like cells. Bladder cancer cell-derived T24 4F cells represent unique features of pluripotent cells such as epithelial-like morphology, colony-forming ability, expression of pluripotency-associated markers and bearing the ability to differentiate in vitro. This is the first study focusing on the reprogramming susceptibility of two different bladder cancer cell lines to nuclear reprogramming. Further molecular characterisation of T24 4F cells could provide a better insight for biomarker research in bladder carcinogenesis and could offer a valuable tool for the development of novel therapeutic approaches in bladder carcinoma.

  10. Frequent truncating mutations of STAG2 in bladder cancer.

    PubMed

    Solomon, David A; Kim, Jung-Sik; Bondaruk, Jolanta; Shariat, Shahrokh F; Wang, Zeng-Feng; Elkahloun, Abdel G; Ozawa, Tomoko; Gerard, Julia; Zhuang, Dazhong; Zhang, Shizhen; Navai, Neema; Siefker-Radtke, Arlene; Phillips, Joanna J; Robinson, Brian D; Rubin, Mark A; Volkmer, Björn; Hautmann, Richard; Küfer, Rainer; Hogendoorn, Pancras C W; Netto, George; Theodorescu, Dan; James, C David; Czerniak, Bogdan; Miettinen, Markku; Waldman, Todd

    2013-12-01

    Here we report the discovery of truncating mutations of the gene encoding the cohesin subunit STAG2, which regulates sister chromatid cohesion and segregation, in 36% of papillary non-invasive urothelial carcinomas and 16% of invasive urothelial carcinomas of the bladder. Our studies suggest that STAG2 has a role in controlling chromosome number but not the proliferation of bladder cancer cells. These findings identify STAG2 as one of the most commonly mutated genes in bladder cancer.

  11. Frequent truncating mutations of STAG2 in bladder cancer

    PubMed Central

    Solomon, David A.; Kim, Jung-Sik; Bondaruk, Jolanta; Shariat, Shahrokh F.; Wang, Zeng-Feng; Elkahloun, Abdel G.; Ozawa, Tomoko; Gerard, Julia; Zhuang, DaZhong; Zhang, Shizhen; Navai, Neema; Siefker-Radtker, Arleen; Phillips, Joanna J.; Robinson, Brian D.; Rubin, Mark A.; Volkmer, Björn; Hautmann, Richard; Küfer, Rainer; Hogendoorn, Pancras C. W.; Netto, George; Theodorescu, Dan; James, C. David; Czerniak, Bogdan; Miettinen, Markku; Waldman, Todd

    2013-01-01

    Here we report the discovery of truncating mutations of the gene encoding the cohesin subunit STAG2, which regulates sister chromatid cohesion and segregation, in 36% of papillary non-invasive urothelial carcinomas and 16% of invasive urothelial carcinomas of the bladder. Our studies suggest that STAG2 plays a role in controlling chromosome number but not proliferation of bladder cancer cells. These findings identify STAG2 as among the most commonly mutated genes in bladder cancer discovered to date. PMID:24121789

  12. Developing urinary metabolomic signatures as early bladder cancer diagnostic markers.

    PubMed

    Shen, Chong; Sun, Zeyu; Chen, Deying; Su, Xiaoling; Jiang, Jing; Li, Gonghui; Lin, Biaoyang; Yan, Jiajun

    2015-01-01

    Early detection is vital to improve the overall survival rate of bladder cancer (BCa) patients, yet there is a lack of a reliable urine-based assay for early detection of BCa. Urine metabolites represented a potential rich source of biomarkers for BCa. This study aimed to develop a metabolomics approach for high coverage discovery and identification of metabolites in urine samples. Urine samples from 23 early stage BCa patients and 21 healthy volunteers with minimum sample preparations were analyzed by a short 30 min UPLC-HRMS method. We detected and quantified over 9000 unique UPLC-HRMS features, which is more than four times than about 2000 features detected in previous urine metabolomic studies. Furthermore, multivariate OPLS-DA classification models were established to differentiate urine samples from bladder cancer cohort and normal health cohort. We identified three BCa-upregulated metabolites: nicotinuric acid, trehalose, AspAspGlyTrp, and three BCa-downregulated metabolites: inosinic acid, ureidosuccinic acid, GlyCysAlaLys. Finally, analysis of six post-surgery BCa urine samples showed that these BCa-metabolomic features reverted to normal state after tumor removal, suggesting that they reflected metabolomic features associated with BCa. ROC analyses using two linear regression models to combine the identified markers showed a high diagnostic performance for detecting BCa with AUC (area under the ROC curve) values of 0.919 to 0.934. In summary, we developed a high coverage metabolomic approach that has potential for biomarker discovery in cancers.

  13. Urology and nephrology update: bladder and kidney cancer.

    PubMed

    Fiore, David C; Fox, Cara-Louise

    2014-01-01

    It has been estimated that bladder and kidney cancers would be diagnosed in approximately 140,000 Americans in 2013, with approximately 30,000 dying from these cancers. Urinary tract cancers affect men more commonly than they do women, and the median age at diagnosis is 65 years. Major risk factors for these cancers include tobacco smoking, certain chemical exposures, family history, age, and obesity. Unexplained hematuria in adults should be evaluated to exclude bladder and kidney cancer. Staging of bladder and kidney cancer should be based on the TNM staging system, which, along with tumor grade, provides important treatment and prognostic information. Urothelial cell carcinoma is the most common type of bladder cancer; it also can occur in the kidneys or ureters. Renal cell carcinoma is the most common type of kidney cancer. Treatment options for bladder cancer vary widely, depending on the grade of the cancer. Early non-muscle-invasive bladder cancer may be removed cystoscopically and/or treated with intravesical immunotherapy or chemotherapy, whereas patients with muscle-invasive bladder tumors typically require surgery. Management of kidney cancer is almost always surgical, unless the patient is too ill to undergo surgery or chooses palliative care.

  14. 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

  15. 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.

  16. Chemoimmunotherapy of implanted murine bladder cancer.

    PubMed

    Akaza, H; Crabtree, W N; Matheny, R B; Soloway, M S

    1983-03-01

    The unaltered incidence of recurrence of superficial bladder tumor after discontinuation of intravesical chemotherapy has prompted a search for effective adjuvant therapy. The technique of cauterization and implantation of tumor cells was performed in C3H/He mice to simulate the early stage of bladder cancer to evaluate a regimen of intravesical mitomycin C followed by the systemic immunopotentiator, levamisole. Mice received either normal saline (control), mitomycin C (MMC), levamisole (Leva), or MMC plus Leva. Chemotherapy was given intravesically on days 6 and 13. Immunotherapy was given intraperitoneally on days 7 and 14. All mice were sacrificed on day 21. In the treatment groups, the incidences of bladder tumor varied from 50 to 63 per cent whereas that of the control group was 91 per cent. An increase in spleen weight was observed in the treatment groups of Leva and MMC plus Leva as well as the control group but not observed in the group receiving MMC. Our study suggests that although Leva did not reduce the tumor incidence, an immunostimulator might be of benefit when used in conjunction with MMC.

  17. Marker evaluation of human breast and bladder cancers

    SciTech Connect

    Mayall, B.H.; Carroll, P.R.; Chen, Ling-Chun; Cohen, M.B.; Goodson, W.H. III; Smith, H.S.; Waldman, F.M. )

    1990-11-02

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

  18. Strategies to improve drug delivery in bladder cancer therapy.

    PubMed

    Wirth, M; Plattner, V E; Gabor, F

    2009-07-01

    Bladder cancer is the ninth most common malignancy in the world featuring very high gender variability in occurrence. Current options for bladder cancer therapy include surgery, immunotherapy, chemotherapy and radiotherapy with a trend towards multimodal treatments. However, successful management remains a challenge for urologists and oncologists because of the high risk for recurrence and progression. Particularly in the field of bladder cancer chemotherapy, efficacy of treatment might be improved by advanced drug delivery strategies aimed at prolonged residence time within the bladder cavity and increased permeability of the bladder wall during intravesical instillation. Moreover, a deeper understanding of the biology of bladder carcinogenesis and malignant progression stimulated the development of a new generation of anticancer drugs for targeted therapies that might result in increased treatment specificity together with lower toxic potential and higher therapeutic indices. This review discusses the available strategies for 'targeted therapy', focusing on molecular targets, and for 'controlled delivery', comprising all other approaches towards improved drug delivery.

  19. 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.

  20. Bladder Cancer Immunotherapy: BCG and Beyond.

    PubMed

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

    2012-01-01

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

  1. Bladder Cancer Immunotherapy: BCG and Beyond

    PubMed Central

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

    2012-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) has become the predominant conservative treatment for nonmuscle invasive bladder cancer. Its mechanism of action continues to be defined but has been shown to involve a T helper type 1 (Th1) immunomodulatory response. While BCG treatment is the current standard of care, a significant proportion of patients fails or do not tolerate treatment. Therefore, many efforts have been made to identify other intravesical and immunomodulating therapeutics to use alone or in conjunction with BCG. This paper reviews the progress of basic science and clinical experience with several immunotherapeutic agents including IFN-α, IL-2, IL-12, and IL-10. PMID:22778725

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

    PubMed

    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.

  3. Epigenetics application in the diagnosis and treatment of bladder cancer.

    PubMed

    Harb-de la Rosa, Alfredo; Acker, Matthew; Kumar, Raj A; Manoharan, Murugesan

    2015-10-01

    Bladder cancer is the sixth most common cancer in the Western world. Patients with bladder cancer require close monitoring, which may include frequent cystoscopy and urine cytology. Such monitoring results in significant health care cost. The application of epigenetics may allow for a risk adapted approach and more cost-effective method of monitoring. A number of epigenetic changes have been described for many cancer sites, including the urinary bladder. In this review, we discuss the use of epigenetics in bladder cancer and the potential diagnostic and therapeutic applications. A comprehensive search of the English medical literature was conducted in PubMed using the terms microRNA regulation, DNA methylation, histone modification and bladder cancer. The most important epigenetic changes include DNA methylation, histone modification and microRNA regulation. Both DNA hypomethylation and hypermethylation have been associated with higher rate of cancer. The association of epigenetic changes with bladder cancer has led to the research of its diagnostic and prognostic implications as well as to the development of novel drugs to target these changes with the aim of achieving a survival benefit. Recently, epigenetics has been shown to play a much greater role than previously anticipated in the initiation and propagation of many tumors. The use of epigenetics for the diagnosis and treatment of bladder cancer is an evolving and promising field. The possibility of reversing epigenetic changes may facilitate additional cancer treatment options in the future.

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

    PubMed

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

    2014-01-01

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

  5. T cell receptor gene recombinations in human tumor specimen exome files: detection of T cell receptor-β VDJ recombinations associates with a favorable oncologic outcome for bladder cancer.

    PubMed

    Samy, Mohammad D; Tong, Wei Lue; Yavorski, John M; Sexton, Wade J; Blanck, George

    2017-03-01

    Understanding tumor-resident T cells is important for cancer prognosis and treatment options. Conventional, solid tumor specimen exome files can be searched directly for recombined T cell receptor (TcR)-α segments; RNASeq files can include TcR-β VDJ recombinations. To learn whether there are medically relevant uses of exome-based detection of TcR V(D)J recombinations in the tumor microenvironment, we searched cancer genome atlas and Moffitt Cancer Center, tumor specimen exome files for TcR-β, TcR-γ, and TcR-δ recombinations, for bladder and stomach cancer. We found that bladder cancer exomes with productive TcR-β recombinations had a significant association with No Subsequent Tumors and a positive response to drug treatments, with p < 0.004, p < 0.05, and p < 0.004, depending on the sample sets examined. We also discovered the opportunity to detect productive TcR-γ and TcR-δ recombinations in the tumor microenvironment, via the tumor specimen exome files.

  6. Investigational cell cycle inhibitors in clinical trials for bladder cancer.

    PubMed

    Yun, Seok Joong; Moon, Sung-Kwon; Kim, Wun-Jae

    2013-03-01

    Cancer-related cell cycle defects are often mediated by alterations in activity of diverse cell cycle regulators. The development of cell cycle inhibitors has undergone a gradual evolution, and new investigational drugs have been extensively tested as a single agent or combination with conventional chemotherapeutic drugs. This review covers a broad perspective of how the cell cycle is deregulated in bladder cancer and discusses the clinical trials of cell cycle inhibitors. Although diverse cell cycle inhibitors have been considered as relevant drug candidates for cancer therapy owing to their potential role in restoring control of the cell cycle, these inhibitors have not been yet widely tested in human bladder cancer. Numerous studies already reported that deregulation of cell cycle controls has been commonly observed in bladder cancer cells, thus warranting clinical trials of these inhibitors in advanced bladder cancer patients. In addition, nonmuscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) show different clinical and molecular biological characteristics, although ∼ 10 - 20% of NMIBC will progress to MIBC. Therefore, adequate cell cycle inhibitors have to be chosen for bladder cancer treatment based on the different genetic features between NMIBC and MIBC related to cell cycle regulators.

  7. [Value of detection of preoperative urinary soluble Fas expression in predicting the recurrence of non-muscle invasive bladder cancer].

    PubMed

    Yang, Huixiang; Guo, Yong; Wang, Zhenchao; Wang, Zhiyong

    2016-01-01

    目的:探讨术前尿可溶性Fas(soluble Fas,sFas)表达在预测非肌层浸润性膀胱癌(non-muscle invasive bladder cancer,NMIBC)复发中的作用。方法:采用前瞻性研究方法,选取2008年1月至2011年4月期间经手术病理确诊的128例NMIBC患者,采用ELISA法测定手术前尿sFas值。结合多项临床病理参数进行非参数统计分析,采用Kaplan-Meier生存曲线分析尿sFas水平与NMIBC患者复发之间的关系,采用Cox比例风险模型进行分析,筛选影响NMIBC预后的独立因素,构建计算预后指数(prognosis index,PI)的公式。结果:NMIBC患者尿sFas值随着病理分期、分级、欧洲癌症研究与治疗组织(EORTC)膀胱癌预后风险评分表评分的增加而增高(P<0.05),与年龄和性别无关(P>0.05)。Kaplan-Meier 生存曲线提示,与低sFas组比较,高sFas组的NMIBC复发率明显增高(P<0.001)。经Cox回归模型分析,尿sFas 值、EORTC评分是影响NMIBC预后的独立因素(P<0.05),计算得到PI公式为0.004×尿sFas值+1.179×EORTC评分。结论:检测尿液sFas表达是预测NMIBC复发的有用指标,值得深入研究。.

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

    PubMed Central

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

    2016-01-01

    Nanoparticles have promising applications in drug delivery for cancer therapy. Herein, we prepared cationic 1,2-dioleoyl-3-trimethylammonium propane/methoxypoly (ethyleneglycol) (DPP) nanoparticles to deliver doxorubicin (Dox) for intravesical therapy of bladder cancer. The DPP micelles have a mean dynamic diameter of 18.65 nm and a mean zeta potential of +19.6 mV. The DPP micelles could prolong the residence of Dox in the bladder, enhance the penetration of Dox into the bladder wall, and improve cellular uptake of Dox. The encapsulation by DPP micelles significantly improved the anticancer effect of Dox against orthotopic bladder cancer in vivo. This work described a Dox-loaded DPP nanoparticle with potential applications in intravesical therapy of bladder cancer. PMID:27660445

  9. Molecular substratification of bladder cancer: moving towards individualized patient management

    PubMed Central

    Mitra, Anirban P.

    2016-01-01

    Despite advances in surgical techniques, perioperative therapies and postoperative management, outcomes for patients with bladder cancer have largely remained unchanged. Current management of bladder cancer still relies on pathologic staging that does not always reflect the risk for an individual patient. Studies assessing molecular alterations in individual tumors are offering insights into the myriad of cellular pathways that are deregulated in bladder tumorigenesis and progression. Alterations in pathways involved in cell-cycle regulation, apoptosis, cell signaling, angiogenesis and tumor-cell invasion have been shown to influence disease behavior. High-throughput assays are now allowing multiplexed assessment of biomarker alterations, thereby enabling characterization of novel molecular subtypes of bladder cancer. Such approaches have also been used for discovery and validation of robust prognostic molecular signatures. The future of bladder cancer management will rely on the use of validated multimarker panels for risk stratification, optimal surgical management, and theranostic strategies to identify and target specific alterations in individual tumors. PMID:27247631

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

    PubMed

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

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

  11. Safety of sequential whole bladder photodynamic therapy (WBPT) in bladder cancer

    NASA Astrophysics Data System (ADS)

    Nseyo, Unyime O.; Lamm, Donald L.; Carpenter, Cindy

    2001-05-01

    Bladder cancer remains a serious public health problem in many parts of the world with an estimated 300,000 new cases a year. In the US, there were 53,200 new cases of bladder cancer with 12,200 deaths in 2000. A majority (75%-90%) of these cancers are diagnosed pathologically as transitional cell carcinoma (TCC). Superficial TCC constitutes 85% of newly diagnosed bladder cancer cases. Superficial bladder cancer includes papillary tumors involving only the mucosa (Ta) or submucosa (T1) and flat carcinoma in suit (CIS). Transurethral resection (TUR) of bladder tumor effectively controls the primary tumors, confirms the superficial or non-muscle invasive nature of the disease, provides cytological and histological tumor characteristics for determining prognostic significance and allows for assessment of the extent of bladder tissue involvement by tumor. Intravesical therapy provides a high concentration of drug in contact with tumor-bearing mucosa for prolonged periods, reduces the likelihood of tumor implantation after resection by destroying viable cancer cells, provides a cytotoxic effect on residual carcinoma, and potentially alters precursor mucosal lesions.

  12. Sensitive detection of transitional cell carcinoma of the bladder by microsatellite analysis of cells exfoliated in urine.

    PubMed

    Seripa, D; Parrella, P; Gallucci, M; Gravina, C; Papa, S; Fortunato, P; Alcini, A; Flammia, G; Lazzari, M; Fazio, V M

    2001-11-20

    Transitional cell carcinoma (TCC) is the most common bladder tumor. Urine cytology can identify most high-grade tumors but sensitivity is lower if one includes lesions of all grades. Microsatellite marker alterations have been found in many tumor types including bladder cancer and have been used to detect cancer cells in body fluids including urine. The aim of our study is to further evaluate feasibility and sensitivity of microsatellite analysis to detect bladder cancer cells in urine. We studied 55 individuals: 21 with symptoms suggestive of bladder cancer, 23 patients with previous history of TCC and 11 healthy subjects. Genomic DNA was extracted from blood lymphocytes, urine sediment, bladder washings and tumor or normal bladder mucosa. Twenty highly informative microsatellite markers were analyzed for loss of heterozigosity (LOH) and microsatellite instability (MIN) by polymerase chain reaction. Microsatellite analysis of urine identified 33 of 34 (97%) patients with either primary or tumor recurrence, whereas urine cytology identified 27 of 34 (79%) patients (p = 0.0001). Detection of microsatellite abnormalities improved the sensitivity of detecting low-grade and/or stage bladder tumor: from 75-95% for grades G1-G2 and from 75-100% for pTis-pTa tumors. Bladder washings from 25 patients were also analyzed, and in all cases results were identical to those obtained from voided urine. None of the 16 patients without evidence of TCC showed LOH and/or MIN in urine samples or bladder washings. Interestingly, in a patient with persistent bladder mucosa abnormalities, microsatellite alterations were demonstrated 8 months before the histopathologic diagnosis of tumor recurrence. These results further indicate that microsatellite marker analysis is more sensitive than conventional urine cytology in detecting bladder cancer cells in urine and represents a potential clinical tool for monitoring patients with low-grade/stage TCC. Copyright 2001 Wiley-Liss, Inc.

  13. Place of cystectomy in superficial bladder cancer.

    PubMed

    Chéchile, G; Sarroca, J; Zungri, E; Rosales, E; Martinez, E

    1988-01-01

    Between January 1978 and June 1985, 44 patients underwent cystectomy for clinically diagnosed superficial bladder cancer. Operative mortality was 13.6%. Early and late complications were observed in 34 and 55% patients, respectively. Clinical understaging was seen in 23%, and stage reduction in 18% of the patients. Clinical staging was correct in 59% of the patients. The mean follow-up was 40 months (range, 24-84 months). Five patients presented local recurrence (13%) of the tumor and 10 patients showed distant metastases (26%). Urethral and upper urinary tract recurrences were observed in 7 and 4 patients, respectively. Fourteen patients (39%) died of cancer after a mean follow-up of 24 months. The actuarial 5-year survival was achieved by 77% of the patients with PTo-PTa-PTis and by 67% of the patients with PT1 (p, not significant).

  14. Bladder Cancer Treatment | Cancer Trends Progress Report

    Cancer.gov

    The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

  15. Hypermethylation of cell-free serum DNA indicates worse outcome in patients with bladder cancer.

    PubMed

    Ellinger, Jörg; El Kassem, Nadja; Heukamp, Lukas C; Matthews, Swapna; Cubukluoz, Figen; Kahl, Philip; Perabo, Frank G; Müller, Stefan C; von Ruecker, Alexander; Bastian, Patrick J

    2008-01-01

    CpG island hypermethylation is a frequent event in bladder carcinogenesis and progression. We investigated the diagnostic and prognostic value of hypermethylation in cell-free serum DNA of patients with bladder cancer. The study cohort consisted of 45 patients with bladder cancer undergoing cystectomy and 45 with histologically confirmed benign prostatic hyperplasia serving as controls. Hypermethylation at APC, DAPK, GSTP1, PTGS2, TIG1 and Reprimo was analyzed using real-time polymerase chain reaction following methylation sensitive restriction endonuclease treatment. Hypermethylation at the APC and GSTP1 promoter was detected in 59% of cases, whereas TIG1 (32%), PTGS2 (24%) and DAPK (2%) were less frequently hypermethylated. In the benign prostatic hyperplasia group 3 patients also harbored methylated GSTP1 DNA, whereas none of the other gene sites was methylated. Hypermethylation at APC, GSTP1 or TIG1 distinguished patients with bladder cancer and controls most accurately with 80% sensitivity and 93% specificity. Hypermethylation significantly correlated with prognostic unfavorable clinicopathological parameters, including APC with pT stage, GSTP1, or GSTP1 or TIG1 with multifocal bladder cancer and APC, or APC or TIG1 with surgical margin positivity. Bladder cancer specific mortality was significantly increased in patients with APC hypermethylation. The detection of hypermethylation in cell-free serum DNA provides valuable diagnostic and prognostic information that can still be improved by combining the results of 3 gene sites (APC, GSTP1 and TIG1). The presence of hypermethylated DNA in the serum of patients with bladder cancer is associated with a worse outcome. Our results suggest that measuring hypermethylation in the serum of patients with bladder cancer is a useful biomarker.

  16. Automatic bladder segmentation on CBCT for multiple plan ART of bladder cancer using a patient-specific bladder model.

    PubMed

    Chai, Xiangfei; van Herk, Marcel; Betgen, Anja; Hulshof, Maarten; Bel, Arjan

    2012-06-21

    In multiple plan adaptive radiotherapy (ART) strategies of bladder cancer, a library of plans corresponding to different bladder volumes is created based on images acquired in early treatment sessions. Subsequently, the plan for the smallest PTV safely covering the bladder on cone-beam CT (CBCT) is selected as the plan of the day. The aim of this study is to develop an automatic bladder segmentation approach suitable for CBCT scans and test its ability to select the appropriate plan from the library of plans for such an ART procedure. Twenty-three bladder cancer patients with a planning CT and on average 11.6 CBCT scans were included in our study. For each patient, all CBCT scans were matched to the planning CT on bony anatomy. Bladder contours were manually delineated for each planning CT (for model building) and CBCT (for model building and validation). The automatic segmentation method consisted of two steps. A patient-specific bladder deformation model was built from the training data set of each patient (the planning CT and the first five CBCT scans). Then, the model was applied to automatically segment bladders in the validation data of the same patient (the remaining CBCT scans). Principal component analysis (PCA) was applied to the training data to model patient-specific bladder deformation patterns. The number of PCA modes for each patient was chosen such that the bladder shapes in the training set could be represented by such number of PCA modes with less than 0.1 cm mean residual error. The automatic segmentation started from the bladder shape of a reference CBCT, which was adjusted by changing the weight of each PCA mode. As a result, the segmentation contour was deformed consistently with the training set to fit the bladder in the validation image. A cost function was defined by the absolute difference between the directional gradient field of reference CBCT sampled on the corresponding bladder contour and the directional gradient field of validation

  17. Automatic bladder segmentation on CBCT for multiple plan ART of bladder cancer using a patient-specific bladder model

    NASA Astrophysics Data System (ADS)

    Chai, Xiangfei; van Herk, Marcel; Betgen, Anja; Hulshof, Maarten; Bel, Arjan

    2012-06-01

    In multiple plan adaptive radiotherapy (ART) strategies of bladder cancer, a library of plans corresponding to different bladder volumes is created based on images acquired in early treatment sessions. Subsequently, the plan for the smallest PTV safely covering the bladder on cone-beam CT (CBCT) is selected as the plan of the day. The aim of this study is to develop an automatic bladder segmentation approach suitable for CBCT scans and test its ability to select the appropriate plan from the library of plans for such an ART procedure. Twenty-three bladder cancer patients with a planning CT and on average 11.6 CBCT scans were included in our study. For each patient, all CBCT scans were matched to the planning CT on bony anatomy. Bladder contours were manually delineated for each planning CT (for model building) and CBCT (for model building and validation). The automatic segmentation method consisted of two steps. A patient-specific bladder deformation model was built from the training data set of each patient (the planning CT and the first five CBCT scans). Then, the model was applied to automatically segment bladders in the validation data of the same patient (the remaining CBCT scans). Principal component analysis (PCA) was applied to the training data to model patient-specific bladder deformation patterns. The number of PCA modes for each patient was chosen such that the bladder shapes in the training set could be represented by such number of PCA modes with less than 0.1 cm mean residual error. The automatic segmentation started from the bladder shape of a reference CBCT, which was adjusted by changing the weight of each PCA mode. As a result, the segmentation contour was deformed consistently with the training set to fit the bladder in the validation image. A cost function was defined by the absolute difference between the directional gradient field of reference CBCT sampled on the corresponding bladder contour and the directional gradient field of validation

  18. Computer-aided detection of bladder masses in CT urography (CTU)

    NASA Astrophysics Data System (ADS)

    Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Weizer, Alon; Samala, Ravi K.

    2017-03-01

    We are developing a computer-aided detection system for bladder cancer in CT urography (CTU). We have previously developed methods for detection of bladder masses within the contrast-enhanced and the non-contrastenhanced regions of the bladder individually. In this study, we investigated methods for detection of bladder masses within the entire bladder. The bladder was segmented using our method that combined deep-learning convolutional neural network with level sets. The non-contrast-enhanced region was separated from the contrast-enhanced region with a maximum-intensity-projection-based method. The non-contrast region was smoothed and gray level threshold was applied to the contrast and non-contrast regions separately to extract the bladder wall and potential masses. The bladder wall was transformed into a straightened thickness profile, which was analyzed to identify lesion candidates in a prescreening step. The candidates were mapped back to the 3D CT volume and segmented using our auto-initialized cascaded level set (AI-CALS) segmentation method. Twenty-seven morphological features were extracted for each candidate. A data set of 57 patients with 71 biopsy-proven bladder lesions was used, which was split into independent training and test sets: 42 training cases with 52 lesions, and 15 test cases with 19 lesions. Using the training set, feature selection was performed and a linear discriminant (LDA) classifier was designed to merge the selected features for classification of bladder lesions and false positives. The trained classifier was evaluated with the test set. FROC analysis showed that the system achieved a sensitivity of 86.5% at 3.3 FPs/case for the training set, and 84.2% at 3.7 FPs/case for the test set.

  19. Angiogenesis in Schistosoma haematobium-associated urinary bladder cancer.

    PubMed

    Dematei, Anderson; Fernandes, Rúben; Soares, Raquel; Alves, Helena; Richter, Joachim; Botelho, Monica C

    2017-09-28

    Schistosoma haematobium, a parasitic flatworm that infects more than 100 million people, mostly in the developing world, is the causative agent of urogenital schistosomiasis, and is associated with a high incidence of squamous cell carcinoma (SCC) of the bladder. During infection, eggs are deposited in the bladder causing an intense inflammatory reaction. Angiogenesis is defined as the formation of new blood vessels from preexisting ones and is recognized as a key event in cell proliferation and carcinogenesis and spread of malignant lesions. A growing amount of evidence points to angiogenesis playing a key role in schistosomiasis-associated bladder cancer. Thus, identifying biomarkers of this process plays an important role in the study of cancer. Here, we review recent findings on the role of angiogenesis in bladder cancer and the growth factors that induce and assist in their development, particularly SCC of the bladder associated to urogenital schistosomiasis. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  20. Involvement of cancer-derived IgG in the proliferation, migration and invasion of bladder cancer cells

    PubMed Central

    Sheng, Zhengzuo; Liu, Yang; Qin, Caipeng; Liu, Zhenhua; Yuan, Yeqing; Yin, Huaqi; Qiu, Xiaoyan; Xu, Tao

    2016-01-01

    It is widely accepted that immunoglobulin (Ig), the classical immune molecule, is extensively expressed in many cell types other than B-cells (non-B-IgG), including some malignant cells. The expression of Ig in malignant cells has been associated with a poor prognosis. In the present study, immunohistochemical analysis detected strong positive staining of IgG in three bladder cancer cell lines, the cancer cells in 77 bladder cancer patient samples and the cells in 3 cystitis glandularis tissue samples, while negative staining was observed in 4 specimens of normal transitional epithelial tissues. Importantly, functional transcripts of IgG with unique VHDJH rearrangement patterns were also found in bladder cancer cells. The knockdown of IgG in bladder cancer cell lines using small interfering RNA significantly inhibited the proliferation, migration and invasion of the cells. Notably, high IgG expression, as determined by immunostaining, was significantly correlated with a high histological grade and recurrence. The results of the present study suggested that IgG expression is involved in the malignant biological behavior and poor prognosis of bladder cancer. Therefore, IgG may serve as a novel target for bladder cancer therapy. PMID:28105218

  1. Induction of G1 cell cycle arrest and apoptosis by berberine in bladder cancer cells.

    PubMed

    Yan, Keqiang; Zhang, Cheng; Feng, Jinbo; Hou, Lifang; Yan, Lei; Zhou, Zunlin; Liu, Zhaoxu; Liu, Cheng; Fan, Yidon; Zheng, Baozhong; Xu, Zhonghua

    2011-07-01

    Bladder cancer is the ninth most common type of cancer, and its surgery is always followed by chemotherapy to prevent recurrence. Berberine is non-toxic to normal cells but has anti-cancer effects in many cancer cell lines. This study was aimed to determine whether berberine inhibits the cell proliferation and induces cell cycle arrest and apoptosis in BIU-87 and T24 bladder cancer cell line. The superficial bladder cancer cell line BIU-87 and invasive T24 bladder cancer cells were treated with different concentrations of berberine. MTT assay was used to determine the effects of berberine on the viability of these cells. The cell cycle arrest was detected through propidium iodide (PI) staining. The induction of apoptosis was determined through Annexin V-conjugated Alexa Fluor 488 (Alexa488) staining. Berberine inhibited the viability of BIU-87 and T24 cells in a dose- and time-dependent manner. It also promoted cell cycle arrest at G0/G1 in a dose-dependent manner and induced apoptosis. We observed that H-Ras and c-fos mRNA and protein expressionswere dose-dependently and time-dependently decreased by berberine treatment. Also, we investigated the cleaved caspase-3 and caspase-9 protein expressions increased in a dose-dependent manner. Berberine inhibits the cell proliferation and induces cell cycle arrest and apoptosis in BIU-87, bladder cancer cell line and T24, invasive bladder cancer cell line. Berberine can inhibit the oncogentic H-Ras and c-fos in T24 cells, and can induce the activation of the caspase-3 and caspase-9 apoptosis. Therefore, berberine has the potential to be a novel chemotherapy drug to treat the bladder cancer by suppressing tumor growth. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Unusual location of a urinary bladder cancer metastasis.

    PubMed

    Forte, Serafino; Kos, Sebastian; Hoffmann, Adrienne

    2009-01-01

    Bladder cancer is the fourth most common malignancy among men in the Western world. Bone metastasis occurs in 27 % of the cases. Usually, the location is the spine. The present report describes the first case of a proven distant bone metastasis to the acromion from a urinary bladder carcinoma in a patient with shoulder pain.

  3. Clinical states model for biomarkers in bladder cancer

    PubMed Central

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

    2013-01-01

    Bladder cancer is a significant health care problem in the United States, with a high recurrence rate, the need for expensive continuous surveillance, and limited treatment options for patients with advanced disease. Research has contributed to an understanding of the molecular pathways involved in the development and progression of bladder cancer, and that understanding has led to the discovery of potentially diagnostic, predictive, and prognostic biomarkers. In this review, a clinical states model of bladder cancer is introduced and integrated into a paradigm for biomarker development. Biomarkers are systematically incorporated with predefined endpoints to aid in clinical management. PMID:19792967

  4. 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.

  5. Bladder cancer risk from occupational and environmental exposures.

    PubMed

    Kiriluk, Kyle J; Prasad, Sandip M; Patel, Amit R; Steinberg, Gary D; Smith, Norm D

    2012-01-01

    Approximately 50% of bladder cancer incidence in the United States has been attributed to known carcinogens, mainly from cigarette smoking. Following the identification of this important causative factor, many investigators have attempted to identify other major causes of bladder cancer in the environment. Genetic and epigenetic alterations related to carcinogenesis in the bladder have been linked to environmental and occupational factors unrelated to cigarette smoking and may account for a significant portion of bladder cancer cases in non-smokers. The interaction between genetics and exposures may modulate bladder cancer risk and influence the differing incidence, progression, and mortality of this disease in different genders and races. Comparative molecular studies are underway to measure the relative effects of environment and inheritance to account for observed differences in the epidemiology of bladder cancer. The use of geospatial tools and population-based data will offer further insight into the environmentally-linked causes of bladder cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2015-05-01

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

  7. The effects of visual fluorescence marking induced by 5-aminolevulinic acid for endoscopic diagnosis of urinary bladder cancer

    NASA Astrophysics Data System (ADS)

    Daniltchenko, Dmitri I.; Koenig, Frank; Schnorr, Dietmar; Valdman, Alexander; Al-Shukri, Salman; Loening, Stefan A.

    2003-10-01

    During cystoscopy procedure, fluorescence diagnostics induced by 5-ALA improves visual detection of the bladder cancer. Macroscopic ALA-fluorescence allows visualizing of small flat tumors, carcinoma in situ, true neoplasm margins and dysplasias of the bladder. Following ALA instillation, cystoscopy has been performed under both standard and blue light illumination. Totally, 153 biopsies have been carried out at 53 patients with suspicion of bladder cancer. The results were compared to ALA-fluorescence data. In 13% of the patients, bladder cancer and dysplasia were found out in addition, due to red fluorescence. The sensitivity and specificity of ALA-fluorescence technique aggregated 96% and 52% respectively. The sensitivity and specificity of 5-ALA-fluorescent detection exceeded standard endoscopy under white light on 20%. The new method does not exclude a false positive and a false negative fluorescent luminescence. The ALA-based fluorescence detection system enhances the diagnosis of malignant/dysplastic bladder lesions significantly.

  8. 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

  9. Bladder aspergillosis detected by urine cytology.

    PubMed

    Martínez-Girón, Rafael; Martínez-Torre, Santiago; Mosquera-Martínez, Joaquín

    2015-05-01

    Bladder aspergillosis is an unusual infection. We report the case of a 79-year-old man with clinical records of transitional cell carcinoma diagnosed 5 years ago. The presence of a fruiting body and septate hyphae in urine cytological smears were the key for a final diagnosis of fungal bladder infection caused by Aspergillus niger.

  10. UBE2T silencing suppresses proliferation and induces cell cycle arrest and apoptosis in bladder cancer cells

    PubMed Central

    Gong, Yan Qing; Peng, Ding; Ning, Xiang Hui; Yang, Xin Yu; Li, Xue Song; Zhou, Li Qun; Guo, Ying Lu

    2016-01-01

    Ubiquitin-conjugating enzyme E2T (UBE2T), a member of the ubiquitin-conjugating E2 family in the ubiquitin-proteasome pathway, has been reported to be overexpressed in certain tumor types and to have an important role in the Fanconi anemia pathway. In the present study, the expression of UBE2T and its association with bladder cancer were investigated; to the best of our knowledge, this has not been reported previously. Immunohistochemistry and western blot analysis demonstrated that UBE2T was significantly upregulated in bladder cancer tissues and cell lines compared with adjacent normal bladder tissues and a normal human urinary tract epithelial cell line, respectively. UBE2T was detectable in the nuclei and cytoplasm of cancer cells, exhibiting stronger expression in the nuclei. A UBE2T-siRNA-expressing lentivirus was constructed and used to infect human bladder cancer 5637 cells, in order to examine the role of UBE2T in bladder cancer cell growth in vitro. The knockdown of UBE2T significantly decreased bladder cancer cell proliferation and colony formation. Furthermore, UBE2T silencing induced cell cycle arrest at G2/M phase and increased cell apoptosis. Therefore, UBE2T serves an important role in the growth of bladder cancer cells, and may be considered as a potential biomarker and therapeutic target for bladder cancer. PMID:28101210

  11. Magnetic Fluid Hyperthermia for Bladder Cancer: A Preclinical Dosimetry Study

    PubMed Central

    Oliveira, Tiago R.; Stauffer, Paul R.; Lee, Chen-Ting; Landon, Chelsea D.; Etienne, Wiguins; Ashcraft, Kathleen A.; McNerny, Katie L.; Mashal, Alireza; Nouls, John; Maccarini, Paolo F.; Beyer, Wayne F.; Inman, Brant; Dewhirst, Mark W.

    2014-01-01

    Purpose This paper describes a preclinical investigation of the feasibility of thermotherapy treatment of bladder cancer with Magnetic Fluid Hyperthermia (MFH), performed by analyzing the thermal dosimetry of nanoparticle heating in a rat bladder model. Materials and Methods The bladders of twenty-five female rats were instilled with magnetite-based nanoparticles, and hyperthermia was induced using a novel small animal magnetic field applicator (Actium Biosystems, Boulder, CO). We aimed to increase the bladder lumen temperature to 42°C in <10 min and maintain that temperature for 60 min. Temperatures were measured within the bladder lumen and throughout the rat with seven fiberoptic probes (OpSens Technologies, Quebec, Canada). An MRI analysis was used to confirm the effectiveness of the catheterization method to deliver and maintain various nanoparticle volumes within the bladder. Thermal dosimetry measurements recorded the temperature rise of rat tissues for a variety of nanoparticle exposure conditions. Results Thermal dosimetry data demonstrated our ability to raise and control the temperature of rat bladder lumen ≥1°C/min to a steady-state of 42°C with minimal heating of surrounding normal tissues. MRI scans confirmed the homogenous nanoparticle distribution throughout the bladder. Conclusion These data demonstrate that our MFH system with magnetite-based nanoparticles provide well-localized heating of rat bladder lumen with effective control of temperature in the bladder and minimal heating of surrounding tissues. PMID:24050253

  12. Increased urothelial cell detection in the primary bladder smooth muscle cell cultures with dual MACS/qRT-PCR approach.

    PubMed

    Genheimer, Chistopher W; Guthrie, Kelly I; Shokes, Jacob E; Bruce, Andrew T; Quinlan, Sarah F; Sangha, Namrata; Ilagan, Roger M; Basu, Joydeep; Burnette, Teresa; Ludlow, John W

    2011-03-01

    Bladder tissue has been regenerated in humans with neurogenic bladder using an implant produced from autologous urothelial (UC) and smooth muscle cells (SMC) expanded from bladder biopsies seeded onto a biodegradable synthetic scaffold. As the majority of bladder cancers are urothelial carcinomas (aka, transitional cell carcinoma), this 2-cell type autologous sourcing strategy presents significant challenges to product development. Entire bladders have been regenerated in cystectomized animals using a single-cell-type sourcing strategy: implants were seeded with bladder-derived SMC-only. Applying the bladder SMC-only sourcing strategy to produce clinical implants for bladder replacement or urinary diversion in bladder cancer patients requires methods for screening SMC cultures for the presence of potentially cancerous UC cells to provide evidence of SMC culture purity before seeding the scaffold. In this report, we show a 10-fold to 100-fold improvement in the sensitivity of qualitative and quantitative reverse-transcription PCR (qRT-PCR)-based assays for detecting UC positive for Cytokeratin 5 (CK5) in mixed SMC/UC cultures when the cell population was first subjected to magnetic activated cell sorting to enrich for cells expressing the epithelial cell adhesion molecule (known as EPCAM or CD326), a marker known to be present in normal UC and upregulated in the cancerous UC.

  13. One-year monitoring of an oligonucleotide fluorescence in situ hybridization probe panel laboratory-developed test for bladder cancer detection

    PubMed Central

    Tinawi-Aljundi, Rima; King, Lauren; Knuth, Shannon T; Gildea, Michael; Ng, Carrie; Kahl, Josh; Dion, Jacqueline; Young, Chris; Schervish, Edward W; Frontera, J Rene; Hafron, Jason; Kernen, Kenneth M; Di Loreto, Robert; Aurich-Costa, Joan

    2015-01-01

    Background Previously, we had developed and manufactured an oligonucleotide fluorescence in situ hybridization (OligoFISH) probe panel based on the most clinically sensitive chromosomes found in a reference set of bladder carcinoma cases. The panel was clinically validated for use as a diagnostic and monitoring assay for bladder cancer, reaching 100% correlation with the results of the UroVysion test. After 1 year of using this probe panel, we present here the comparison of cytology, cystoscopy, and pathology findings to the OligoFISH probe panel results to calculate its clinical performance. Materials and methods In order to calculate clinical performance, we compared the OligoFISH results to the cytology and cystoscopy/pathology findings for 147 initial diagnoses and 399 recurrence monitorings. Finally, we compared clinical performance to published values for the UroVysion test, including both low- and high-grade tumors. Results Chromosomes 3, 6, 7, and 20 were highly involved in bladder carcinoma aneuploidy. At the initial diagnosis, we obtained 90.5% (95% confidence interval [CI]: 84.5%–94.7%) accuracy, 96.8% sensitivity (95% CI: 91.0%–99.3%), 79.2% specificity (95% CI: 65.9%–87.8%), 89.2% positive predictive value (PPV; 95% CI: 81.5%–94.5%), and 93.3% negative predictive value (NPV; 95% CI: 81.7%–97.3%). When monitoring for recurrence, we obtained 85.2% accuracy (95% CI: 81.3%–88.5%), 82.0% sensitivity (95% CI: 76.0%–87.1%), 88.4% specificity (95% CI: 83.2%–92.5%), 87.7% PPV (95% CI: 82.1%–92.0%), and 83.0% NPV (95% CI: 77.3%–87.8%). When looking at low- and high-grade tumors, the test showed 100% sensitivity for high-grade tumors (95% CI: 92.5%–100%) and 87.5% sensitivity (95% CI: 68.8%–95.5%) for low-grade tumors. All the clinical parameters for the OligoFISH panel were higher than the UroVysion test’s published performance. We found significantly higher clinical sensitivity and NPV at initial diagnosis and significantly higher

  14. Tunneling nanotubes promote intercellular mitochondria transfer followed by increased invasiveness in bladder cancer cells.

    PubMed

    Lu, Jinjin; Zheng, Xiufen; Li, Fan; Yu, Yang; Chen, Zhong; Liu, Zheng; Wang, Zhihua; Xu, Hua; Yang, Weimin

    2017-02-28

    Intercellular transfer of organelles via tunneling nanotubes (TNTs) is a novel means of cell-to-cell communication. Here we demonstrate the existence of TNTs between co-cultured RT4 and T24 bladder cancer cells using light microscopy, fluorescence imaging, and scanning electron microscopy (SEM). Spontaneous unidirectional transfer of mitochondria from T24 to RT4 cells was detected using fluorescence imaging and flow cytometry. The distribution of mitochondria migrated from T24 cells was in good agreement with the original mitochondria in RT4 cells, which may imply mitochondrial fusion. We detected cytoskeleton reconstruction in RT4-Mito-T24 cells by observing F-actin redistribution. Akt, mTOR, and their downstream mediators were activated and increased. The resultant increase in the invasiveness of bladder cancer cells was detected in vitro and in vivo. These data indicate that TNTs promote intercellular mitochondrial transfer between heterogeneous cells, followed by an increase in the invasiveness of bladder cancer cells.

  15. Expression of the VLA beta 1 integrin family in bladder cancer.

    PubMed Central

    Liebert, M.; Washington, R.; Stein, J.; Wedemeyer, G.; Grossman, H. B.

    1994-01-01

    Integrins are a family of transmembrane heterodimers, many of which function as receptors for extracellular matrix molecules and play a role in adherence to and motility on matrix components. Because of these functions, integrins are suspected of participating in metastatic processes. We investigated the expression of beta 1 integrins in human bladder cancer cell lines and tissues. Expression of beta 1 integrins on cultured bladder cancer cell lines was evaluated by flow cytometry, of 8 cell lines tested, alpha 1 was found in 4, alpha 2 and alpha 3 in all 8, alpha 4 in 1, and alpha 5 in 3. These results were in sharp contrast to the expression detected by immunostaining tissues containing normal urothelium and low stage (noninvasive) and high stage (invasive) bladder cancers. All normal urothelial tissues tested expressed alpha 2 and alpha 3 and none expressed alpha 1, alpha 4, or alpha 5. Similarly, a majority (77%) of low stage (noninvasive) bladder cancers stained positively for alpha 3, whereas only 6 of 13 expressed alpha 2 and none expressed alpha 1, alpha 4, or alpha 5. Among invasive bladder cancers, alpha 1 was detected in 7%, alpha 2 in 24%, alpha 3 in 68%, alpha 5 in 10%, and alpha 4 was not found in any samples. These results indicate that integrin expression in cultured human bladder cancer cell lines does not represent expression observed in tissue samples and may reflect adaption to or selection during tissue culture conditions. A progressive loss of alpha 2 expression is seen from normal urothelial cells through invasive bladder cancers. This loss may contribute to an invasive phenotype by a loss of the cell-cell adherence function mediated by the alpha 2 beta 1 and alpha 3 beta 1 integrins. Images Figure 2 Figure 3 PMID:8178925

  16. Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2

    DOE PAGES

    Ho, Melissa E.; Quek, Sue -Ing; True, Lawrence D.; ...

    2016-02-15

    Anterior gradient 2 (AGR2) is a cancer-associated secreted protein found predominantly in adenocarcinomas. Given its ubiquity in solid tumors, cancer-secreted AGR2 could be a useful biomarker in urine or blood for early detection. Normal organs express AGR2 and might also secrete AGR2, which would impact on the utility of AGR2 as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is, however, secreted by the urothelial cells as no measurable amounts could be detected in urine. The urinary proteomes of healthy people contain no listing for AGR2. The blood proteomes also contain no significantmore » peptide counts for AGR2 suggesting that little urothelial secretion into capillaries of the lamina propria. Expression is lost in urothelial carcinoma, but 25% primary tumors retained AGR2 expression in a cohort of lymph node positive cases. AGR2 is secreted by the urothelial carcinoma cells as urinary AGR2 was measured in the voided urine of 25% of the cases analyzed in a cohort of cancer vs. non-cancer urine, which matched the frequency of AGR2-positive urothelial carcinoma. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. In addition to secretion, AGR2 is also localized to the cell surface. Thus, secretion/cell surface localization of AGR2 is pecific to cancer while expression itself is not. Lastly, since AGR2 is found in many solid tumor types, this tumor-associated antigen constitutes a highly promising therapeutic target.« less

  17. Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2

    SciTech Connect

    Ho, Melissa E.; Quek, Sue -Ing; True, Lawrence D.; Seiler, Roland; Fleischmann, Achim; Bagryanova, Lora; Kim, Sara R.; Chia, David; Goodglick, Lee; Shimizu, Yoshiko; Rosser, Charles J.; Gao, Yuqian; Liu, Alvin Y.

    2016-02-15

    Anterior gradient 2 (AGR2) is a cancer-associated secreted protein found predominantly in adenocarcinomas. Given its ubiquity in solid tumors, cancer-secreted AGR2 could be a useful biomarker in urine or blood for early detection. Normal organs express AGR2 and might also secrete AGR2, which would impact on the utility of AGR2 as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is, however, secreted by the urothelial cells as no measurable amounts could be detected in urine. The urinary proteomes of healthy people contain no listing for AGR2. The blood proteomes also contain no significant peptide counts for AGR2 suggesting that little urothelial secretion into capillaries of the lamina propria. Expression is lost in urothelial carcinoma, but 25% primary tumors retained AGR2 expression in a cohort of lymph node positive cases. AGR2 is secreted by the urothelial carcinoma cells as urinary AGR2 was measured in the voided urine of 25% of the cases analyzed in a cohort of cancer vs. non-cancer urine, which matched the frequency of AGR2-positive urothelial carcinoma. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. In addition to secretion, AGR2 is also localized to the cell surface. Thus, secretion/cell surface localization of AGR2 is pecific to cancer while expression itself is not. Lastly, since AGR2 is found in many solid tumor types, this tumor-associated antigen constitutes a highly promising therapeutic target.

  18. CMTM8 inhibits the carcinogenesis and progression of bladder cancer

    PubMed Central

    GAO, DENGHUI; HU, HAO; WANG, YING; YU, WEIDONG; ZHOU, JIANHUA; WANG, XIAOFENG; WANG, WEIPING; ZHOU, CHUNYAN; XU, KEXIN

    2015-01-01

    Bladder cancer is the most common tumor of the urinary tract. The incidence of bladder cancer has increased in the last few decades, thus novel molecular markers for early diagnosis and more efficacious treatment are urgently needed. Chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing 8 (CMTM8) is downregulated in several types of cancers and is associated with tumor progression. However, CMTM8 expression has been unexplored in bladder cancer to date. Our results revealed that the expression of CMTM8 was negative in 46 of 74 (62.2%) bladder cancer samples via immunohistochemistry assay. CMTM8 downregulation was associated with advancing tumor stage and tumor grade. CMTM8 was successfully overexpressed by lentivirus in EJ and T24 cells, and the CCK-8 and Transwell assays showed that CMTM8 overexpression decreased cell proliferation, migration and invasion in vitro. In tumor xenografts upregulation of CMTM8 inhibited tumor growth and lymph node metastasis in vivo. In conclusion, overexpression of CMTM8 in bladder cancer results in reduced malignant cell growth, migration and invasion, which could make it a potential therapeutic target in the treatment of bladder cancer. PMID:26503336

  19. 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

  20. Genetic variant as a marker for bladder cancer therapy

    Cancer.gov

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

  1. 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.

  2. Gene expression profiling in bladder cancer identifies potential therapeutic targets

    PubMed Central

    Hussain, Syed A.; Palmer, Daniel H.; Syn, Wing-Kin; Sacco, Joseph J.; Greensmith, Richard M.D.; Elmetwali, Taha; Aachi, Vijay; Lloyd, Bryony H.; Jithesh, Puthen V.; Arrand, John; Barton, Darren; Ansari, Jawaher; Sibson, D. Ross; James, Nicholas D.

    2017-01-01

    Despite advances in management, bladder cancer remains a major cause of cancer related complications. Characterisation of gene expression patterns in bladder cancer allows the identification of pathways involved in its pathogenesis, and may stimulate the development of novel therapies targeting these pathways. Between 2004 and 2005, cystoscopic bladder biopsies were obtained from 19 patients and 11 controls. These were subjected to whole transcript-based microarray analysis. Unsupervised hierarchical clustering was used to identify samples with similar expression profiles. Hypergeometric analysis was used to identify canonical pathways and curated networks having statistically significant enrichment of differentially expressed genes. Osteopontin (OPN) expression was validated by immunohistochemistry. Hierarchical clustering defined signatures, which differentiated between cancer and healthy tissue, muscle-invasive or non-muscle invasive cancer and healthy tissue, grade 1 and grade 3. Pathways associated with cell cycle and proliferation were markedly upregulated in muscle-invasive and grade 3 cancers. Genes associated with the classical complement pathway were downregulated in non-muscle invasive cancer. Osteopontin was markedly overexpressed in invasive cancer compared to healthy tissue. The present study contributes to a growing body of work on gene expression signatures in bladder cancer. The data support an important role for osteopontin in bladder cancer, and identify several pathways worthy of further investigation. PMID:28259975

  3. Urinary markers in the everyday diagnosis of bladder cancer.

    PubMed

    Dal Moro, Fabrizio; Valotto, Claudio; Guttilla, Andrea; Zattoni, Filiberto

    2013-01-01

    Bladder cancer (BC) represents the fourth most common neoplasia in men and the ninth most common cancer in women, with a significant morbidity and mortality. Cystoscopy and voided urine cytology (involving the examination of cells in voided urine to detect the presence of cancerous cells) are currently the routine initial investigations in patients with hematuria or other symptoms suggestive of BC. Around 75-85% of the patients are diagnosed as having non-muscle-invasive bladder cancer (NMIBC). Despite the treatment, these patients have a probability of recurrence at 5 years ranging from 50 to 70% and of progression to muscle invasive disease of 10-15%. Patients with NMIBC must undergo life-long surveillance, consisting of serial cystoscopies, possibly urine cytology and ultrasonography. Cystoscopy is unsuitable for screening because of its invasiveness and costs; serial cystoscopies may cause discomfort and distress to patients. Furthermore, cystoscopy may be inconclusive, falsely positive or negative. Although urine cytology has a reasonable sensitivity for the detection of high-grade BC, it lacks sensitivity to detect low-grade tumors (sensitivity ranging from 4 to 31%). The overall sensitivity and specificity of urine cytology range from 7 to 100 and from 30 to 70%, respectively. There is a need for new urine biomarkers that may help in BC diagnosis and surveillance. A lot of urinary biomarkers with high sensitivity and/or specificity have been investigated. Although none of these markers have proven to be powerful enough to replace standard cystoscopy, some of them may represent accurate predictors of BC. A review of recent studies is presented.

  4. Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe).

    PubMed

    Häggström, Christel; Liedberg, Fredrik; Hagberg, Oskar; Aljabery, Firas; Ströck, Viveka; Hosseini, Abolfazl; Gårdmark, Truls; Sherif, Amir; Malmström, Per-Uno; Garmo, Hans; Jahnson, Staffan; Holmberg, Lars

    2017-09-27

    To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe). The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register. Participants in the SNRUBC have registered data on tumour characteristics at diagnosis, and for 98% of these treatment data have been captured. From 2009, the SNRUBC holds data on 88% of eligible participants for follow-up 5 years after diagnosis of non-muscle invasive bladder cancer, and from 2011, data on surgery details and complications for 85% of participants treated with radical cystectomy. The BladderBaSe includes all data in the SNRUBC from 1997 to 2014, and additional covariates and follow-up data from linked national register sources on comorbidity, socioeconomic factors, detailed information on readmissions and treatment side effects, and causes of death. Studies based on data in the SNRUBC have shown inequalities in survival and treatment indication by gender, regions and hospital volume. The BladderBaSe includes 38 658 participants registered in SNRUBC with bladder cancer diagnosed from 1 January 1997 to 31 December 2014. The BladderBaSe initiators are currently in collaboration with researchers from the SNRUBC investigating different aspects of bladder cancer survival. The SNRUBC and the BladderBaSe project are open for collaborations with national and international research teams. Collaborators can submit proposals for studies and study files can be uploaded to servers for remote access and analysis. For more information, please contact the corresponding author. © Article author(s) (or their employer

  5. Water intake and bladder cancer risk in Los Angeles County.

    PubMed

    Jiang, Xuejuan; Castelao, Jose E; Groshen, Susan; Cortessis, Victoria K; Shibata, Darryl K; Conti, David V; Gago-Dominguez, Manuela

    2008-10-01

    The overall evidence of an association between fluid intake and bladder cancer is not entirely consistent. We examined the fluid intake-bladder cancer relationship in the Los Angeles bladder cancer case-control study. A total of 1,586 cases and their age-, sex-, and race-matched neighborhood controls were interviewed in-person from 1987 to 1999. Information on total fluid intake was derived from the consumption of specific fluids including water, coffee, tea, alcohol, milk, juice, hot chocolate and soda. Total fluid intake was not associated with bladder cancer. Daily water intake was associated with a slight decrease in bladder cancer risk, with the protection more pronounced among women (p for trend = 0.039) than among men (p for trend = 0.62). Compared to drinking <1 glass of water per day, drinking > or =6 glasses/day was associated with 0.91 (95% confidence interval, 0.67-1.22) times the risk of bladder cancer among all subjects, 0.94 (0.67-1.32) times the risk among men, and 0.69 (0.36-1.33) times the risk among women. The water intake-bladder cancer association also seemed to be modified by daytime urination frequency with significant inverse association among subjects who urinated > or =6 times/day (p for trend = 0.015), but not among those who urinated less frequently. Similarly, the protection from water intake was confined to women who did not experience nocturia and to men who did. Results from our study suggest that water intake may be associated with a slight reduction in bladder cancer risk.

  6. Detection of Bladder CA by Microsatellite Analysis (MSA) — EDRN Public Portal

    Cancer.gov

    Goal 1: To determine sensitivity and specificity of microsatellite analysis (MSA) of urine sediment, using a panel of 15 microsatellite markers, in detecting bladder cancer in participants requiring cystoscopy. This technique will be compared to the diagnostic standard of cystoscopy, as well as to urine cytology. Goal 2: To determine the temporal performance characteristics of microsatellite analysis of urine sediment. Goal 3: To determine which of the 15 individual markers or combination of markers that make up the MSA test are most predictive of the presence of bladder cancer.

  7. Randomized-Control Screening Trials to Lower Gall Bladder Cancer Mortality in High Risk Populations.

    PubMed

    Krishnatreya, Manigreeva; Kataki, Amal Chandra

    2016-01-01

    Gall bladder cancer is generally fatal. The high morbidity and mortality due to gall bladder cancer exerts a significant impact on efforts towards cancer control in high risk populations of the World and a rationale program for control of gall bladder cancer mortality has remained as an unmet need in these populations. Currently there are no effective strategies for controlling gall bladder cancer mortality. This mini review is to highlight the need and feasibility for secondary prevention of gall bladder cancer by screening in high risk populations. A way forward is to assess the role of secondary prevention of gall bladder cancers by conducting randomized- controlled screening trials in high risk populations.

  8. Involvement of the Androgen and Glucocorticoid Receptors in Bladder Cancer

    PubMed Central

    McBeth, Lucien; Grabnar, Maria; Selman, Steven; Hinds, Terry D.

    2015-01-01

    Bladder cancer is encountered worldwide having been associated with a host of environmental and lifestyle risk factors. The disease has a male to female prevalence of 3 : 1. This disparity has raised the possibility of the androgen receptor (AR) pathway being involved in the genesis of the disease; indeed, research has shown that AR is involved in and is likely a driver of bladder cancer. Similarly, an inflammatory response has been implicated as a major player in bladder carcinogenesis. Consistent with this concept, recent work on anti-inflammatory glucocorticoid signaling points to a pathway that may impact bladder cancer. The glucocorticoid receptor- (GR-) α isoform has an important role in suppressing inflammatory processes, which may be attenuated by AR in the development of bladder cancer. In addition, a GR isoform that is inhibitory to GRα, GRβ, is proinflammatory and has been shown to induce cancer growth. In this paper, we review the evidence of inflammatory mediators and the relationship of AR and GR isoforms as they relate to the propensity for bladder cancer. PMID:26347776

  9. 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.

  10. Concurrent bladder cancer in patients undergoing photodynamic diagnostic ureterorenoscopy: how many lesions do we miss under white light cystoscopy?

    PubMed Central

    Zreik, Abdullah; Ahmad, Sarfraz; Chłosta, Piotr; Aboumarzouk, Omar

    2016-01-01

    Introduction There is an ongoing debate on panurothelial changes in the upper and lower urinary tract as multifocal presentation of urothelial cancer is well recognised. Concurrent bladder cancer impacts the outcome of the upper urinary tract urothelial cancer treatment, while its detection still relies on the white light cystoscopy. Material and methods We retrospectively reviewed all patients who underwent photodynamic diagnostic ureterorenoscopy, choosing those who had synchronous bladder biopsies. Each patient received 20 mg/kg body weight of oral 5-Aminolevulinic acid around 3–4 hours before endoscopy. All procedures were performed by a single endourologist experienced in photodynamic diagnosis and flexible ureterorenoscopy. Results Between July 2009 and June 2013, 69 patients underwent bladder biopsies at the time of photodynamic diagnostic endoscopic inspection of the upper urinary tract. In total, 43.5% (30/69) patients were found to have bladder lesions, of which 43.3% (13/30) were proven to be carcinoma in situ. White light inspection of the bladder missed bladder cancer in 16 (23.1%) patients, of which 12 were carcinoma in situ. There were 14 bladder cancer lesions missed under white light which were concomitant to the upper urinary tract urothelial cancer. Twelve (17.4%) patients developed minor complications relevant to the photosensitizer. Conclusions The study raises a concern about missing small bladder cancer/carcinoma in situ lesions on the initial diagnosis or in surveillance of the upper urinary tract urothelial cancer. Higher than previously reported, the rate of concomitant bladder cancer may suggest utilisation of photodynamic diagnosis to ensure the cancer free status of the bladder, but this needs to be ratified in a multi-institutional randomised trial. PMID:28127447

  11. Combined ultrasmall superparamagnetic particles of iron oxide-enhanced and diffusion-weighted magnetic resonance imaging reliably detect pelvic lymph node metastases in normal-sized nodes of bladder and prostate cancer patients.

    PubMed

    Thoeny, Harriet C; Triantafyllou, Maria; Birkhaeuser, Frederic D; Froehlich, Johannes M; Tshering, Dechen W; Binser, Tobias; Fleischmann, Achim; Vermathen, Peter; Studer, Urs E

    2009-04-01

    Lymph node staging of bladder or prostate cancer using conventional imaging is limited. Newer approaches such as ultrasmall superparamagnetic particles of iron oxide (USPIO) and diffusion-weighted magnetic resonance imaging (DW-MRI) have inconsistent diagnostic accuracy and are difficult to interpret. To assess whether combined USPIO and DW-MRI (USPIO-DW-MRI) improves staging of normal-sized lymph nodes in bladder and/or prostate cancer patients. Twenty-one consecutive patients with bladder and/or prostate cancer were enrolled between May and October 2008. One patient was excluded secondary to bone metastases detected on DW-MRI with subsequent abstention from surgery. Patients preoperatively underwent 3-T MRI before and after administration of lymphotropic USPIO using conventional MRI sequences combined with DW-MRI. Surgery consisted of extended pelvic lymphadenectomy and resection of primary tumors. Diagnostic accuracies of the new combined USPIO-DW-MRI approach compared with the "classic" reading method evaluating USPIO images without and with DW-MRI versus histopathology were evaluated. Duration of the two reading methods was noted for each patient. Diagnostic accuracy (90% per patient or per pelvic side) was comparable for the classic and the USPIO-DW-MRI reading method, while time of analysis with 80 min (range 45-180 min) for the classic and 13 min (range 5-90 min) for the USPIO-DW-MRI method was significantly shorter (p<0.0001). Interobserver agreement (three blinded readers) was high with a kappa value of 0.75 and 0.84, respectively. Histopathological analysis showed metastases in 26 of 802 analyzed lymph nodes (3.2%). Of these, 24 nodes (92%) were correctly diagnosed as positive on USPIO-DW-MRI. In two patients, one micrometastasis each (1.0x0.2 mm; 0.7x0.4 mm) was missed in all imaging studies. USPIO-DW-MRI is a fast and accurate method for detecting pelvic lymph node metastases, even in normal-sized nodes of bladder or prostate cancer patients.

  12. 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

  13. 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

  14. [The use of NMP22 Bladder-Chek for the diagnosis and follow-up bladder cancer].

    PubMed

    Gonzalo Rodríguez, Victoria; Sanz Justo, Lourdes; de Miguel Santamaría, Isabel; Martínez de Iturrate, Javier; Fernández del Busto, Ernesto

    2008-04-01

    The goal of this work is to evaluate the usefulness of NMP22 BladderChek in the diagnosis and follow-up of bladder cancer, comparing it with cystoscopy and urine cytology. Group 1: 109 asymptomatic patients on follow up for bladder cancer underwent cystoscopy, cytology and NMP22 BladderChek. Group 2:15 patients with history of hematuria underwent cystoscopy and NMP22 BladderChek. Group 1: 9 patients had tumor relapse. Sensitivity was 25% for NMP22 test, 50% for citology and 100% for cystoscopy Specificity was 91.1%, 94.1% and 95% respectively. Group 2: 12 patients had bladder cancer. The sensitivity was of 83.3% for NMP22 BladderChek and 100% for cystoscopy. The specificity was of 100% for NMP22 BladderChek and 66.7% for cystoscopy. The low sensitivity of NMP22 Bladder-Chek invalidates it as alternative method to cystoscopy in the follow-up of bladder cancer. But it can be recommended for screening in patients without history of bladder cancer but with an increased risk (smokers, patients with dysuria and hematuria).

  15. Early Detection of Genotoxic Urinary Bladder Carcinogens by Immunohistochemistry for γ-H2AX.

    PubMed

    Toyoda, Takeshi; Cho, Young-Man; Akagi, Jun-Ichi; Mizuta, Yasuko; Hirata, Tadashi; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2015-12-01

    DNA double-strand breaks (DSBs) induced by exposure to genotoxic agents are known to cause genome instability and cancer development. To evaluate the applicability of γ-H2AX, a sensitive marker of DSBs, in the early detection of genotoxicity and carcinogenicity of chemicals using animal models, we examined γ-H2AX expression in urinary bladders of rats. Six-week-old male F344 rats were orally treated for 4 weeks with a total of 12 chemicals divided into 4 categories based on genotoxicity and carcinogenicity in the urinary bladder. Animals were sacrificed at the end of administration or after 2 weeks of recovery, and immunohistochemistry for γ-H2AX was performed. At week 4, γ-H2AX expression in bladder epithelial cells was significantly increased by all 4 genotoxic bladder carcinogens as compared with the controls, whereas the 3 chemicals that were genotoxic but not carcinogenic in the bladders did not cause upregulation of γ-H2AX. After the recovery period, γ-H2AX expression was markedly reduced in all groups but remained significantly elevated in rats treated with 3 of the 4 genotoxic bladder carcinogens. Although slight increases in γ-H2AX expression were induced by a weak bladder carcinogen with equivocal genotoxicity (phenethyl isothiocyanate) and 2 nongenotoxic bladder carcinogens (melamine and uracil) at week 4, these differences were not significant and were thought to be associated with activated proliferation by urothelial hyperplasia, as demonstrated by increased Ki67-positive cells. These results suggested that γ-H2AX may be a potential biomarker for the early detection of genotoxic bladder carcinogens.

  16. Novel non invasive diagnostic strategies in bladder cancer

    PubMed Central

    TRUTA, ANAMARIA; POPON, TUDOR ADRIAN HODOR; SARACI, GEORGE; GHERVAN, LIVIU; POP, IOAN VICTOR

    2016-01-01

    Bladder cancer is one of the most commonly diagnosed malignancies worldwide, derived from the urothelium of the urinary bladder and defined by long asymptomatic and atypical clinical picture. Its complex etiopathogenesis is dependent on numerous risk factors that can be divided into three distinct categories: genetic and molecular abnormalities, chemical or environmental exposure and previous genitourinary disorders and family history of different malignancies. Various genetic polymorphisms and microRNA might represent useful diagnostic or prognostic biomarkers. Genetic and molecular abnormalities - risk factors are represented by miRNA or genetic polymorphisms proved to be part of bladder carcinogenesis such as: genetic mutations of oncogenes TP53, Ras, Rb1 or p21 oncoproteins, cyclin D or genetic polymorhisms of XPD,ERCC1, CYP1B1, NQO1C609T, MDM2SNP309, CHEK2, ERCC6, NRF2, NQO1Pro187Ser polymorphism and microRNA (miR-143, −145, −222, −210, −10b, 576-3p). The aim of our article is to highlight the most recent acquisitions via molecular biomarkers (miRNAs and genetic polymorphisms) involved in bladder cancer in order to provide early diagnosis, precise therapy according to the molecular profile of bladder tumors, as well as to improve clinical outcome, survival rates and life quality of oncological patients. These molecular biomarkers play a key role in bladder carcinogenesis, clinical evolution, prognosis and therapeutic response and explain the molecular mechanisms involved in bladder carcinogenesis; they can also be selected as therapeutic targets in developing novel therapeutic strategies in bladder malignancies. Moreover, the purpose in defining these molecular non invasive biomarkers is also to develop non invasive screening programs in bladder malignancies with the result of decreasing bladder cancer incidence in risk population. PMID:27152066

  17. Novel non invasive diagnostic strategies in bladder cancer.

    PubMed

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

    2016-01-01

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

  18. Nitrative DNA damage and Oct3/4 expression in urinary bladder cancer with Schistosomahaematobium infection

    SciTech Connect

    Ma, Ning; Thanan, Raynoo; Kobayashi, Hatasu; Hammam, Olfat; Wishahi, Mohamed; Leithy, Tarek El; Hiraku, Yusuke; Amro, EL-Karef; Oikawa, Shinji; Ohnishi, Shiho; Murata, Mariko; Kawanishi, Shosuke

    2011-10-22

    Highlights: {yields} Oct3/4-positive cells increase in Schistosoma haematobium (SH)-associated bladder cancer. {yields} iNOS-dependent DNA lesion, 8-nitroguanine, was formed in Oct3/4-positive cells. {yields} 8-Nitroguanine formed in stem-like cells plays a role in SH-induced carcinogenesis. {yields} Mutant stem cells may participate in inflammation-related carcinogenesis. -- Abstract: To investigate whether mutant stem cells participate in inflammation-related carcinogenesis, we performed immunohistochemical analysis to examine nitrative and oxidative DNA lesions (8-nitroguanine and 8-oxodG) and a stem cell marker Oct3/4 in bladder tissues obtained from cystitis and bladder cancer patients infected with Schistosomahaematobium (S. haematobium). We also detected the expression of nuclear factor-{kappa}B (NF-{kappa}B) and inducible nitric oxide synthase (iNOS), which lead to 8-nitroguanine formation. The staining intensity of 8-nitroguanine and 8-oxodG was significantly higher in bladder cancer and cystitis tissues than in normal tissues. iNOS expression was colocalized with NF-{kappa}B in 8-nitroguanine-positive tumor cells from bladder cancer patients. Oct3/4 expression was significantly increased in cells from S. haematobium-associated bladder cancer tissues in comparison to normal bladder and cancer tissues without infection. Oct3/4 was also expressed in epithelial cells of cystitis patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in S. haematobium-associated cystitis and cancer tissues. In conclusion, inflammation by S.haematobium infection may increase the number of mutant stem cells, in which iNOS-dependent DNA damage occurs via NF-{kappa}B activation, leading to tumor development.

  19. 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.

  20. Dipstick Urinalysis as a Test for Microhematuria and Occult Bladder Cancer

    PubMed Central

    Matulewicz, Richard S.; DeLancey, John Oliver; Pavey, Emily; Schaeffer, Edward M.; Popescu, Oana; Meeks, Joshua J.

    2017-01-01

    Introduction: There is a lack of evidence supporting the routine use of laboratory tests to detect bladder cancer. Identifying a cost-effective and widely available diagnostic aid may improve bladder cancer outcomes. We sought to evaluate the utility of dipstick urinalysis to detect microhematuria and diagnose bladder cancer in a large, diverse, contemporary cohort. Methods: All non-pregnant women and men 35 and older with a new diagnosis of microhematuria (≥3 RBC/hpf) were identified via a multi-center electronic medical record data warehouse query. Negative controls with no history of hematuria were randomly chosen and included to complete our cohort. Comparison between dipstick urinalysis and microscopic urinalysis on self-matched patients for the detection of microhematuria and diagnosis of bladder cancer was performed via Spearman’s rank correlation coefficient, sensitivity/specificity testing, and ROC curve analysis. Results: A total of 46,842 patients were included. Spearman’s rank order correlation (rho = 0.66) between degree of microhematuria on dipstick urinalysis and microscopic urinalysis indicated a strong positive relationship. The ROC curve for dipstick urinalysis to identify microhematuria had an AUC of 0.80 (95% CI 0.79–0.81). No difference (p = 0.83) in diagnostic accuracy between dipstick urinalysis (AUC 0.74, 95% CI 0.70–0.78) and microscopic urinalysis (AUC 0.73, 95% CI 0.69–0.78) as a test for bladder cancer was found. Conclusion: Dipstick urinalysis provides a highly specific test for microhematuria and similar accuracy to microscopic urinalysis when used as a diagnostic tool to detect bladder cancer. PMID:28149934

  1. Complementary and alternative medicine (CAM) in prostate and bladder cancer.

    PubMed

    Philippou, Yiannis; Hadjipavlou, Marios; Khan, Shahid; Rane, Abhay

    2013-12-01

    To provide an overview of the scientific and clinical studies underlying the most common vitamin and herbal preparations used in prostate and bladder cancer and evaluate the evidence behind them. A literature search was undertaken on PubMed using various keywords relating to the use of complementary and alternative medicine (CAM) in prostate and bladder cancer.Vitamin E and selenium supplementation can potentially have adverse effects by increasing the risk of prostate cancer. Initial clinical studies of pomegranate and green tea, investigating their chemotherapeutic properties in prostate and bladder cancer have yielded encouraging results. Curcumin, resveratrol, and silibinin have potential anticancer properties through multiple molecular targets; their clinical effectiveness in prostate and bladder cancer is yet to be evaluated. Zyflamend, like PC-SPES, is a combined CAM therapy used in prostate cancer. Acupuncture is popular among patients experiencing hot flushes who are receiving androgen-deprivation therapy for prostate cancer. Conclusive evidence for the use of CAM in prostate and bladder cancer is lacking and not without risk.

  2. The Promise of Novel Molecular Markers in Bladder Cancer

    PubMed Central

    Miremami, Jahan; Kyprianou, Natasha

    2014-01-01

    Bladder cancer is the fourth most common malignancy in the US and is associated with the highest cost per patient. A high likelihood of recurrence, mandating stringent surveillance protocols, has made the development of urinary markers a focus of intense pursuit with the hope of decreasing the burden this disease places on patients and the healthcare system. To date, routine use of markers is not recommended for screening or diagnosis. Interests include the development of a single urinary marker that can be used in place of or as an adjunct to current screening and surveillance techniques, as well identifying a molecular signature for an individual’s disease that can help predict progression, prognosis, and potential therapeutic response. Markers have shown potential value in improving diagnostic accuracy when used as an adjunct to current modalities, risk-stratification of patients that could aid the clinician in determining aggressiveness of surveillance, and allowing for a decrease in invasive surveillance procedures. This review discusses the current understanding of emerging biomarkers, including miRNAs, gene signatures and detection of circulating tumor cells in the blood, and their potential clinical value in bladder cancer diagnosis, as prognostic indicators, and surveillance tools, as well as limitations to their incorporation into medical practice. PMID:25535079

  3. 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.

  4. Multiplexed Methylation Profiles of Tumor Suppressor Genes in Bladder Cancer

    PubMed Central

    Cabello, Maria José; Grau, Laura; Franco, Noreli; Orenes, Esteban; Alvarez, Miguel; Blanca, Ana; Heredero, Oscar; Palacios, Alberto; Urrutia, Manuel; Fernández, Jesus María; López-Beltrán, Antonio; Sánchez-Carbayo, Marta

    2011-01-01

    Changes in DNA methylation of tumor suppressors can occur early in carcinogenesis and are potentially important early indicators of cancer. The objective of this study was to assess the methylation of 25 tumor suppressor genes in bladder cancer using a methylation-specific (MS) multiplex ligation-dependent probe amplification assay (MLPA). Initial analyses in bladder cancer cell lines (n = 14) and fresh-frozen primary bladder tumor specimens (n = 31) supported the panel of genes selected being altered in bladder cancer. The process of MS-MLPA was optimized for its application in body fluids using two independent training and validation sets of urinary specimens (n = 146), including patients with bladder cancer (n = 96) and controls (n = 50). BRCA1 (71.0%), WT1 (38.7%), and RARB (38.7%) were the most frequently methylated genes in bladder tumors, with WT1 methylation being significantly associated with tumor stage (P = 0.011). WT1 and PAX5A were identified as methylated tumor suppressors. In addition, BRCA1, WT1, and RARB were the most frequently methylated genes in urinary specimens. Receiver operating characteristic curve analyses revealed significant diagnostic accuracies in both urinary sets for BRCA1, RARB, and WT1. The novelty of this report relates to applying MS-MLPA, a multiplexed methylation technique, for tumor suppressors in bladder cancer and body fluids. Methylation profiles of tumor suppressor genes were clinically relevant for histopathological stratification of bladder tumors and offered a noninvasive diagnostic strategy for the clinical management of patients affected with uroepithelial neoplasias. PMID:21227392

  5. Comparison between standard and reduced volume radiotherapy in bladder preservation trimodality protocol for muscle-invasive bladder cancer patients

    PubMed Central

    Arafat, Waleed; Darwish, Azza; Naoum, George E; Sameh, Wael; Husseiny, Gamal El; Abd-El-Gawad, Fathy; Samir, Mostafa

    2016-01-01

    Aim Our aim is to compare the toxicity, pelvic nodal relapse, and overall survival of whole bladder irradiation only to the standard technique of whole pelvis irradiation followed by bladder boost in patients with muscle-invasive bladder carcinoma undergoing bladder preservation protocol. Material and method A total of 60 patients with transitional cell carcinoma, stage T2-3, N0, M0 bladder cancer were subjected to maximal transurethral resection bladder tumour (TURB). Then, the patients were randomised into two groups: group I (30 patients) to receive whole pelvis radiotherapy 44 Gy followed by 20 Gy bladder boost. While group II (30 patients) were randomised to receive whole bladder radiotherapy alone for a total dose of 64 Gy. In both groups, concomitant cisplatin and paclitaxel were given weekly throughout the whole course of radiotherapy where conventional 2 Gy/fraction were used. Additionally, four cycles of adjuvant cisplatin and paclitaxel were given after the end of the chemoradiotherapy induction course. Results The first assessment after the induction chemoradiotherapy showed that complete response was achieved in 73.3% of patients in group I and 76.7% of the patients in group II. After a median follow-up of 2 years, regional relapse occurred in 7.1% of patients in group I and 10.3% in group II. (p = 1). Distant metastases were detected in 17.9% of patient in group I and 13.8% in group II (p = 0.73). The 2-year disease-free survival was 60% in group I and 63.3% in group II (p = 0.79). The whole 2-year overall survival was 75% in group I and 79.3% in group II (p = 0.689). Radiation gastrointestinal (GI) acute toxicity was higher in group I than in group II (p = 0.001), while late GI radiation toxicity was comparable in both groups. Conclusion Treating the bladder only, without elective pelvic nodal irradiation, did not compromise pelvic control rate, but significantly decreased the acute radiation toxicity. PMID:27899955

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

    PubMed Central

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

    2010-01-01

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

  7. Optical coherence tomography in diagnostics of precancer and cancer of human bladder

    NASA Astrophysics Data System (ADS)

    Zagaynova, Elena V.; Streltsova, Olga S.; Gladkova, Natalia D.; Shakhova, Natalia M.; Feldchtein, Felix I.; Kamensky, Vladislav A.; Gelikonov, Grigory V.; Snopova, Ludmila B.; Donchenko, Ekaterina V.

    2004-07-01

    Our goal was statistical assessment of the in vivo cystoscopic optical coherence tomography (OCT) ability to detect neoplasia in human urinary bladder. We analyzed major reasons of false positive and false negative image recognition results. Optical coherence tomography was performed to image the bladder during cystoscopy. The study enrolled 63 patients with suspicion for bladder cancer and scheduled for cystoscopy. The diagnosis was established by histopathology examination of a biopsy. Each biopsy site was examined by OCT. Benign conditions were diagnosed for 31 patients, and dysplasia or carcinoma were diagnosed for 32 patients. Six physicians blinded to all clinical data participated in the dichotomy recognition (malignant or benign) of the OCT images. 98% sensitivity and 72% specificity for the OCT recognition of dysplastic/malignant versus benign/reactive conditions of the bladder are demonstrated. Total error rate was 14.8%. The interobserver agreement multi-rater kappa coefficient is 0.80. The superficial and invasive bladder cancer and high-grade dysplasia were recognized with minimum error rate ranging from 0 to 3.3%. High sensitivity and good specificity of the OCT method in the diagnostics of bladder neoplasia makes OCT a promising complementary cystoscopic technique for non-invasive evaluation of zones suspicious for high-grade dysplasia and cancer.

  8. 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

  9. Bladder filling variation during radiation treatment of prostate cancer: Can the use of a bladder ultrasound scanner and biofeedback optimize bladder filling?

    SciTech Connect

    Stam, Marcel R. . E-mail: m.stam@rther.umcn.nl; Lin, Emile N.J. Th. van; Vight, Lisette P. van der; Kaanders, Johannes; Visser, Andries G.

    2006-06-01

    Purpose: To investigate the use of a bladder ultrasound scanner in achieving a better reproducible bladder filling during irradiation of pelvic tumors, specifically prostate cancer. Methods and Materials: First, the accuracy of the bladder ultrasound scanner relative to computed tomography was validated in a group of 26 patients. Next, daily bladder volume variation was evaluated in a group of 18 patients. Another 16 patients participated in a biofeedback protocol, aiming at a more constant bladder volume. The last objective was to study correlations between prostate motion and bladder filling, by using electronic portal imaging device data on implanted gold markers. Results: A strong correlation between bladder scanner volume and computed tomography volume (r = 0.95) was found. Daily bladder volume variation was very high (1 Sd = 47.2%). Bladder filling and daily variation did not significantly differ between the control and the feedback group (47.2% and 40.1%, respectively). Furthermore, no linear correlations between bladder volume variation and prostate motion were found. Conclusions: This study shows large variations in daily bladder volume. The use of a biofeedback protocol yields little reduction in bladder volume variation. Even so, the bladder scanner is an easy to use and accurate tool to register these variations.

  10. The underactive bladder: detection and diagnosis.

    PubMed

    Osman, Nadir; Mangera, Altaf; Hillary, Christopher; Inman, Richard; Chapple, Christopher

    2016-01-01

    The inability to generate a voiding contraction sufficient to allow efficient bladder emptying within a reasonable time frame is a common problem seen in urological practice. Typically, the symptoms that arise are voiding symptoms, such as weak and slow urinary flow. These symptoms can cause considerable bother to patients and impact upon quality of life. The urodynamic finding of inadequate detrusor contraction has been termed detrusor underactivity (DUA). Although a definition is available for this entity, there are no widely accepted diagnostic criteria. Drawing parallels to detrusor overactivity and the overactive bladder, the symptoms arising from DUA have been referred to as the "underactive bladder" (UAB), while attempts to crystallize the definition of UAB are now ongoing. In this article, we review the contemporary literature pertaining to the epidemiology and etiopathogenesis of DUA as well as discuss the definitional aspects that are currently under consideration.

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

    PubMed

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

    2009-09-15

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

  12. Hedgehog Signaling Regulates Bladder Cancer Growth And Tumorigenicity

    PubMed Central

    Fei, Dennis Liang; Sanchez-Mejias, Avencia; Wang, Zhiqiang; Flaveny, Colin; Long, Jun; Singh, Samer; Rodriguez-Blanco, Jezabel; Tokhunts, Robert; Giambelli, Camilla; Briegel, Karoline J.; Schulz, Wolfgang A.; Gandolfi, A. Jay; Karagas, Margaret; Zimmers, Teresa A.; Jorda, Merce; Bejarano, Pablo; Capobianco, Anthony J.; Robbins, David J.

    2012-01-01

    The role of HEDGEHOG (HH) signaling in bladder cancer remains controversial. The gene encoding the HH receptor and negative regulator PATCHED1 (PTCH1) resides on a region of chromosome 9q, one copy of which is frequently lost in bladder cancer. Inconsistent with PTCH1 functioning as a classic tumor suppressor gene, loss-of-function mutations in the remaining copy of PTCH1 are not commonly found. Here, we provide direct evidence for a critical role of HH signaling in bladder carcinogenesis. We show that transformed human urothelial cells and many urothelial carcinoma (UC) cell lines exhibit constitutive HH signaling, which is required for their growth and tumorigenic properties. Surprisingly, rather than originating from loss of PTCH1, the constitutive HH activity observed in UC cell lines was HH ligand-dependent. Consistent with this finding, increased levels of HH and the HH target gene product GLI1 were found in resected human primary bladder tumors. Furthermore, based on the difference in intrinsic HH dependence of UC cell lines, a gene expression signature was identified that correlated with bladder cancer progression. Our findings therefore indicate that therapeutic targeting of the HH signaling pathway may be beneficial in the clinical management of bladder cancer. PMID:22815529

  13. Ciprofloxacin criteria in antimicrobial prophylaxis and bladder cancer recurrence.

    PubMed

    Gurtowska, Natalia; Kloskowski, Tomasz; Drewa, Tomasz

    2010-10-01

    Oral ciprofloxacin might achieve higher concentration in urine than in serum; theoretically, this drug might act as an anticancer drug against bladder cancer cells. Among fluoroquinolones, ciprofloxacin is distinguished by strong inhibition of topoisomerase II. A good correlation between cytotoxic activity of ciprofloxacin toward eukaryotic cells and its ability to induce the cleavable complexes topoisomerase II-DNA has been demonstrated. These data provide a basis for supposing that ciprofloxacin may act as anticancer drug. The efforts of evaluating ciprofloxacin's influence on human bladder cell lines have been shown by many authors. The cells were exposed to ciprofloxacin at various concentrations that are attainable in the urine after oral drug administration. Antiproliferative potential of the ciprofloxacin against human bladder cells varies according to drug concentration and time of incubation. It seems that ciprofloxacin can act as an anticancer drug in eukaryotic cells. Low urine pH can enhance the antitumor effect of ciprofloxacin. Ciprofloxacin enhances the effect of action of doxorubicin and epirubicin, which are used to prevent bladder cancer recurrence after transurethral resection of superficial bladder cancer. We think that ciprofloxacin might be used for antibacterial prophylaxis and as an anticancer agent in patients with superficial bladder cancer. This idea must be checked in future placebo controlled trials.

  14. 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.

  15. 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.

  16. Conditional Expression of the Androgen Receptor Increases Susceptibility of Bladder Cancer in Mice

    PubMed Central

    Luong, Richard; Yu, Eun-Jeong; He, Yongfeng; Gonzalgo, Mark L.; Sun, Zijie

    2016-01-01

    Bladder cancer represents a significant human tumor burden, accounting for about 7.7% and 2.4% of all cancer cases in males and females, respectively. While men have a higher risk of developing bladder cancer, women tend to present at a later stage of disease and with more aggressive tumors. Previous studies have suggested a promotional role of androgen signaling in enhancing bladder cancer development. To directly assess the role of androgens in bladder tumorigenesis, we have developed a novel transgenic mouse strain, R26hARLoxP/+:Upk3aGCE/+, in which the human AR transgene is conditionally expressed in bladder urothelium. Intriguingly, both male and female R26hARLoxP/+:Upk3aGCE/+ mice display a higher incidence of urothelial cell carcinoma (UCC) than the age and sex matched control littermates in response to the carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). We detect expression of the human AR transgene in CK5-positive and p63-positive basal cells in bladder urothelium. Further analyses of UCC tissues from R26hARLoxP/+:Upk3aGCE/+ mice showed that the majority of tumor cells are of urothelial basal cell origin. Positive immunostaining of transgenic AR protein was observed in the majority of tumor cells of the transgenic mice, providing a link between transgenic AR expression and oncogenic transformation. We observed an increase in Ki67 positive cells within the UCC lesions of transgenic AR mice. Manipulating endogenous androgen levels by castration and androgen supplementation directly affected bladder tumor development in male and female R26hARLoxP/+:Upk3aGCE/+ mice, respectively. Taken together, our data demonstrate for the first time that conditional activation of transgenic AR expression in bladder urothelium enhances carciongen-induced bladder tumor formation in mice. This new AR transgenic mouse line mimics certain features of human bladder cancer and can be used to study bladder tumorigenesis and for drug development. PMID:26862755

  17. 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

  18. Suburothelial Bladder Contraction Detection with Implanted Pressure Sensor

    PubMed Central

    Fletter, Paul C.; Ferry, Elizabeth K.; Zhu, Hui; Gustafson, Kenneth J.; Damaser, Margot S.

    2017-01-01

    Aims Managing bladder pressure in patients with neurogenic bladders is needed to improve rehabilitation options, avoid upper tract damage, incontinence, and their associated co-morbidities and mortality. Current methods of determining bladder contractions are not amenable to chronic or ambulatory settings. In this study we evaluated detection of bladder contractions using a novel piezoelectric catheter-free pressure sensor placed in a suburothelial bladder location in animals. Methods Wired prototypes of the pressure monitor were implanted into 2 nonsurvival (feline and canine) and one 13-day survival (canine) animal. Vesical pressures were obtained from the device in both suburothelial and intraluminal locations and simultaneously from a pressure sensing catheter in the bladder. Intravesical pressure was monitored in the survival animal over 10 days from the suburothelial location and necropsy was performed to assess migration and erosion. Results In the nonsurvival animals, the average correlation between device and reference catheter data was high during both electrically stimulated bladder contractions and manual compressions (r = 0.93±0.03, r = 0.89±0.03). Measured pressures correlated strongly (r = 0.98±0.02) when the device was placed in the bladder lumen. The survival animal initially recorded physiologic data, but later this deteriorated. However, endstage intraluminal device recordings correlated (r = 0.85±0.13) with the pressure catheter. Significant erosion of the implant through the detrusor was found. Conclusions This study confirms correlation between suburothelial pressure readings and intravesical bladder pressures. Due to device erosion during ambulatory studies, a wireless implant is recommended for clinical rehabilitation applications. PMID:28060842

  19. Long-term bladder, colorectal, and sexual functions after radical radiotherapy for urinary bladder cancer.

    PubMed

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

    2004-08-01

    To describe bladder, colorectal, and sexual dysfunctions among long time survivors after radical radiotherapy for urinary bladder cancer, and compare the results with a healthy control group. We identified 261 patients who had received radical radiotherapy for bladder cancer in the period 1994-2001. Patients were treated with a CT-based three-field technique with 60 Gy in 2 Gy fractions, 5 fractions/week. Sixty-two patients were alive and candidates for the study. For comparison, 185 controls were selected from the Danish National Register. Information was collected in an interview based on the LENT SOMA tables and questions concerning changes in daily life following radiotherapy. Fifty-three patients (85%), median age 77 years (range 51-84) entered the study. Median follow-up time was 29 months (range 18-103 months). There were 63 controls (34%). Fourteen percent of the patients reported that radiotherapy had moderate to severe impact on their present bladder function. Compared with the control group, significantly more patients had dysuria, and urethral stenosis, and were using bladder catheter. Twenty-nine percent of the patients reported moderate to severe impact on their present bowel function. Significantly more patients had diarrhoea, fecal urgency and fecal incontinence, and were using antidiarrhoea medication and sanitary pads. Twenty-five percent of the patients reported moderate to severe impact on their present sexual function. Impotence and lack of sexual desire were significantly higher among the male patients. Following radical radiotherapy, most patients had a well functioning bladder, whereas 14% reported moderate to severe bladder dysfunctions. Due to the presence of bowel in the treatment field, radiotherapy is associated with considerable long-term intestinal side effects. Moreover, radiotherapy may result in sexual dysfunctions.

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

    PubMed Central

    Yang, Ganglong; Xu, Zhipeng; Lu, Wei; Li, Xiang; Sun, Chengwen; Guo, Jia; Xue, Peng; Guan, Feng

    2015-01-01

    The best way to increase patient survival rate is to identify patients who are likely to progress to muscle-invasive or metastatic disease upfront and treat them more aggressively. The human cell lines HCV29 (normal bladder epithelia), KK47 (low grade nonmuscle invasive bladder cancer, NMIBC), and YTS1 (metastatic bladder cancer) have been widely used in studies of molecular mechanisms and cell signaling during bladder cancer (BC) progression. However, little attention has been paid to global quantitative proteome analysis of these three cell lines. We labeled HCV29, KK47, and YTS1 cells by the SILAC method using three stable isotopes each of arginine and lysine. Labeled proteins were analyzed by 2D ultrahigh-resolution liquid chromatography LTQ Orbitrap mass spectrometry. Among 3721 unique identified and annotated proteins in KK47 and YTS1 cells, 36 were significantly upregulated and 74 were significantly downregulated with >95% confidence. Differential expression of these proteins was confirmed by western blotting, quantitative RT-PCR, and cell staining with specific antibodies. Gene ontology (GO) term and pathway analysis indicated that the differentially regulated proteins were involved in DNA replication and molecular transport, cell growth and proliferation, cellular movement, immune cell trafficking, and cell death and survival. These proteins and the advanced proteome techniques described here will be useful for further elucidation of molecular mechanisms in BC and other types of cancer. PMID:26230496

  1. PET/CT in renal, bladder and testicular cancer

    PubMed Central

    Bouchelouche, Kirsten; Physician, Chief; Choyke, Peter L.

    2015-01-01

    Imaging plays an important role in the clinical management of cancer patients. Hybrid imaging with PET/CT is having a broad impact in oncology, and in recent years PET/CT is beginning to have an impact in uro-oncology as well. In both bladder and renal cancer there is a need to study the efficacy of other tracers than F-18 fluorodeoxyglucose (FDG), particularly tracers with only limited renal excretion. Thus, new tracers are being introduced in these malignancies. This review focuses on the clinical role of FDG and other PET agents in renal, bladder and testicular cancer. PMID:26099672

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

    PubMed

    Bouchelouche, Kirsten; Choyke, Peter L

    2015-07-01

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

  3. Hyperthermia as Adjunct to Intravesical Chemotherapy for Bladder Cancer

    PubMed Central

    Owusu, Richmond A.; Abern, Michael R.; Inman, Brant A.

    2013-01-01

    Nonmuscle invasive bladder cancer remains a very costly cancer to manage because of high recurrence rates requiring long-term surveillance and treatment. Emerging evidence suggests that adjunct and concurrent use of hyperthermia with intravesical chemotherapy after transurethral resection of bladder tumor further reduces recurrence risk and progression to advanced disease. Hyperthermia has both direct and immune-mediated cytotoxic effect on tumor cells including tumor growth arrest and activation of antitumor immune system cells and pathways. Concurrent heat application also acts as a sensitizer to intravesical chemotherapy agents. As such the ability to deliver hyperthermia to the focus of tumor while minimizing damage to surrounding benign tissue is of utmost importance to optimize the benefit of hyperthermia treatment. Existing chemohyperthermia devices that allow for more localized heat delivery continue to pave the way in this effort. Current investigational methods involving heat-activated drug delivery selectively to tumor cells using temperature-sensitive liposomes also offer promising ways to improve chemohyperthermia efficacy in bladder cancer while minimizing toxicity to benign tissue. This will hopefully allow more widespread use of chemohyperthermia to all bladder cancer patients, including metastatic bladder cancer. PMID:24073396

  4. Current therapeutic strategies for invasive and metastatic bladder cancer

    PubMed Central

    Vishnu, Prakash; Mathew, Jacob; Tan, Winston W

    2011-01-01

    Background Bladder cancer is one of the most common cancers in Europe, the United States, and Northern African countries. Muscle-invasive bladder cancer is an aggressive epithelial tumor, with a high rate of early systemic dissemination. Superficial, noninvasive bladder cancer can most often be cured; a good proportion of invasive cases can also be cured by a combined modality approach of surgery, chemotherapy, and radiation. Recurrences are common and mostly manifest as metastatic disease. Those with distant metastatic disease can sometime achieve partial or complete remission with combination chemotherapy. Recent developments Better understanding of the biology of the disease has led to the incorporation of molecular and genetic features along with factors such as tumor grade, lympho-vascular invasion, and aberrant histology, thereby allowing identification of ‘favorable’ and ‘unfavorable’ cancers which helps a more accurate informed and objective selection of patients who would benefit from neoadjuvant and adjuvant chemotherapy. Gene expression profiling has been used to find molecular signature patterns that can potentially be predictive of drug sensitivity and metastasis. Understanding the molecular pathways of invasive bladder cancer has led to clinical investigation of several targeted therapeutics such as anti-angiogenics, mTOR inhibitors, and anti-EGFR agents. Conclusion With improvements in the understanding of the biology of bladder cancer, clinical trials studying novel and targeted agents alone or in combination with chemotherapy have increased the armamentarium for the treatment of bladder cancer. Although the novel biomarkers and gene expression profiles have been shown to provide important predictive and prognostic information and are anticipated to be incorporated in clinical decision-making, their exact utility and relevance calls for a larger prospective validation. PMID:21792316

  5. Bladder and bowel symptoms in cervical and endometrial cancer survivors.

    PubMed

    Donovan, Kristine A; Boyington, Alice R; Judson, Patricia L; Wyman, Jean F

    2014-06-01

    Previous studies likely underestimate the prevalence of bowel and bladder symptoms in gynecologic cancer survivors. We sought to estimate the prevalence of these symptoms in cervical and endometrial cancer survivors who had completed treatment 1 year previously compared with non-cancer controls, and to examine factors associated with more severe symptoms in survivors. As part of a larger quality of life study, survivors who were 1-year posttreatment for cervical or endometrial cancer (n = 104) completed measures of bladder and bowel symptoms. An age-matched and race/ethnicity-matched sample of women with no history of cancer was recruited for comparison purposes. Survivors reported a higher prevalence of bladder symptoms, specifically storage and incontinence symptoms, than non-cancer controls. Prevalence rates for bowel symptoms in survivors were higher than those reported in previous studies. Greater symptom severity was associated with younger age, lower annual incomes, and less education. Other correlates included higher body mass index and history of smoking. As hypothesized, more severe symptoms were associated with radical hysterectomy and pelvic radiation. Bladder and bowel symptoms are more prevalent in cervical and endometrial cancer survivors than non-cancer controls. Future research should replicate these findings in a larger, prospective study. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Occupation and cancer in London: an investigation into nasal and bladder cancer using the Cancer Atlas.

    PubMed

    Baxter, P J; McDowall, M E

    1986-01-01

    The Atlas of Cancer Mortality for England and Wales showed pronounced excesses of male mortality from nasal and bladder cancer in certain London boroughs. These excesses were investigated by case-referent studies using death certificate data for male deaths, 1968-78. Nasal cancer was found to be significantly associated with occupations involving heavy exposure to wood dust. Bladder cancer was significantly associated with occupations in road transport driving and in the handling of leather, whereas consistently raised relative risk ratios were also found for wood-workers, engineering fitters, printers, machinists, plumbers, and motor mechanics. These findings highlight the potential role of occupational factors in cancer causation in London.

  7. Ultraweak biophoton emission imaging of transplanted bladder cancer.

    PubMed

    Amano, T; Kobayashi, M; Devaraj, B; Usa, M; Inaba, H

    1995-01-01

    Biophoton emission or spontaneous ultraweak light emission has been observed from almost all living organisms, with intensities ranging from 10(-19) to 10(-16) W/cm2. The measurement of biophoton emission offers the attractive possibility of noninvasive monitoring of the underlying physiological function of a living system. In the present study, ultraweak biophoton emission from mice with transplanted bladder cancer was detected by a two-dimensional photon-counting system. Photon counts were observed to be 1.51-4.73 times higher from the regions of untreated tumor than from normal regions. Our study suggests that this novel technique may be applicable to the diagnosis of superficial tumors.

  8. 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

  9. Genomic Landscape of Experimental Bladder Cancer in Rodents and Its Application to Human Bladder Cancer: Gene Amplification and Potential Overexpression of Cyp2a5/CYP2A6 Are Associated with the Invasive Phenotype

    PubMed Central

    Kanemoto, Kazuhiro; Fukuta, Katsuhiro; Kawai, Noriyasu; Tozawa, Keiichi; Ochiai, Masako; Okamoto, Koji; Ohnami, Sumiko; Sakamoto, Hiromi; Yoshida, Teruhiko; Kanai, Yae; Katoh, Masaru; Yasui, Takahiro; Kohri, Kenjiro; Kakizoe, Tadao; Nakagama, Hitoshi

    2016-01-01

    Non-muscle invasive (superficial) bladder cancer is a low-grade malignancy with good prognosis, while muscle invasive (invasive) bladder cancer is a high-grade malignancy with poor prognosis. N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) induces superficial bladder cancers with papillary morphology in rats and invasive bladder cancers with infiltrating phenotype in mice. In this study, we analyzed genomic landscapes of rodent BBN-induced bladder cancers using array-based comparative genomic hybridization (array CGH). While no significant copy number alterations were detected in superficial bladder tumors in rats, copy number gains in chromosomal regions 2D-E1, 7qA3, 9F2, and 11C-D were detected in invasive bladder tumors in mice. Amplification of representative genes located on 2D-E1 and 7qA3 chromosomal regions was confirmed by quantitative PCR. Cyp2a22 and Cyp2a5 genes but not Cyp2g1, Cyp2a12, and Rab4b genes on mouse chromosome 7qA3 were amplified in invasive bladder cancers. Although the human ortholog gene of Cyp2a22 has not been confirmed, the mouse Cyp2a5 gene is the ortholog of the human CYP2A6 gene located in chromosomal region 19q13.2, and CYP2A6 was identified by database search as one of the closest human homolog to mouse Cyp2a22. Considering a possibility that this region may be related to mouse 7qA3, we analyzed CYP2A6 copy number and expression in human bladder cancer using cell lines and resected tumor specimens. Although only one of eight cell lines showed more than one copy increase of the CYP2A6 gene, CYP2A6 amplification was detected in six out of 18 primary bladder tumors where it was associated with the invasive phenotype. Immunohistochemical analyses of 118 primary bladder tumors revealed that CYP2A6 protein expression was also higher in invasive tumors, especially in those of the scattered type. Together, these findings indicate that the amplification and overexpression of the CYP2A6 gene are characteristic of human bladder cancers with

  10. Benign prostatic hyperplasia and subsequent risk of bladder cancer

    PubMed Central

    Kang, D; Chokkalingam, A P; Gridley, G; Nyren, O; Johansson, J E; Adami, H O; Silverman, D; Hsing, A W

    2007-01-01

    We evaluated the risk of bladder cancer in a cohort of 79 280 Swedish men hospitalised for benign prostatic hyperplasia (BPH), identified in the Swedish Inpatient Register between 1964 and 1983 and followed until 1989 via multiple record linkages with nationwide data on cancer registry, death and emigration. Standardised incidence ratios (SIRs), the ratios of the observed to the expected numbers of incident bladder cancers, were used to calculate the risk associated with BPH. The expected number was calculated by multiplying the number of person-years by the age-specific cancer incidence rates in Sweden for each 5-year age group and calendar year of observation. Analyses were stratified by BPH treatment, latency, calendar year and presence of genitourinary (GU) comorbid conditions. After excluding the first 3 years of follow-up after the index hospitalisation, we observed 506 incident bladder cancer cases during follow-up in the cohort. No overall increased risk of bladder cancer was apparent in our main analysis involving the entire BPH cohort. However, among BPH patients with transurethral resection of the prostate (TURP), there was an increased risk in all follow-up periods; SIRs of bladder cancer during years 4–6 of follow-up was 1.22 (95% confidence interval=1.02–1.46), 1.32 for 7–9 years of follow-up, and 1.47 for 10–26 years of follow-up. SIRs of bladder cancer among TURP-treated BPH patients were particularly elevated among those with comorbid conditions of the GU tract (e.g., stone, infection, etc.); 1.72, 1.74 and 2.01 for 4–6, 7–9, 10–26 years of follow-up, respectively, and also for those whose diagnoses occurred before 1975, when TURP was more likely to be performed by a urologist than a general practitioner: 1.87, 1.90 and 1.74, respectively. These findings suggest that BPH overall is not associated with bladder cancer risk. However, among men treated with TURP, particularly those with other comorbid GU tract conditions, risk of

  11. 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.

  12. High resolution photoacoustic imaging of microvasculature in normal and cancerous bladders

    NASA Astrophysics Data System (ADS)

    Xie, Zhixing; Roberts, William; Carson, Paul L.; Liu, Xiaojun; Tao, Chao; Wang, Xueding

    2013-03-01

    We explored the potential of an emerging laser-based technology, photoacoustic imaging (PAI), for bladder cancer diagnosis through high resolution imaging of microvasculature in the interior bladder tissues. Images of ex vivo canine bladders demonstrated the excellent ability of PAI to map three-dimensional microvasculature in optically scattering bladder tissues. By comparing the results from human bladder specimens affected by cancer to those from the normal control, the feasibility of PAI in differentiating malignant from benign bladder tissues was explored. The reported distinctive morphometric characteristics of tumor microvasculature can be seen in the images from cancer samples, suggesting that PAI may allow in vivo assessment of neoangiogenesis that is closely associated with bladder cancer generation and progression. By presenting subsurface morphological and physiological information in bladder tissues, PAI, when performed in a similar way to that in conventional endoscopy, provides an opportunity for improved diagnosis, staging and treatment guidance of bladder cancer.

  13. Discordance Between Preoperative and Postoperative Bladder Cancer Location: Implications for Partial-Bladder Radiation

    SciTech Connect

    Goldsmith, Benjamin; Tucker, Kai; Conway, Robert Greg; He, Jiwei; Guzzo, Thomas; Bekelman, Justin; Deville, Curtiland; Vapiwala, Neha; Malkowicz, S. Bruce; Christodouleas, John

    2013-03-01

    Purpose: There is strong interest in partial-bladder radiation whether as a boost or definitive therapy to limit long-term toxicity. It is unclear that a standard preoperative examination can accurately identify all sites of disease within the bladder. The purpose of this study was to determine the correlation between preoperative localization of bladder tumors with postoperative findings to facilitate partial-bladder radiation techniques when appropriate. Methods and Materials: We examined patients with clinically staged T1-T4 invasive transitional cell carcinoma (TCC) or TCC with variant histology with no history of radiation or partial cystectomy undergoing radical cystectomy. Patients were scored as “under-detected” if a bladder site was involved with invasive disease (≥T1) at the time of cystectomy, but not identified preoperatively. Patients were additionally scored as “widely under-detected” if they had postoperative lesions that were not identified preoperatively in a given site, nor in any adjacent site. Rates of under-detected and widely under-detected lesions, as well as univariate and multivariate association between clinical variables and under-detection, were evaluated using logistic regression. Results: Among 222 patients, 96% (213/222) had at least 1 area of discordance. Fifty-eight percent of patients were under-detected in at least 1 location, whereas 12% were widely under-detected. Among 24 patients with a single site of disease on preoperative evaluation, 21/24 (88%) had at least 1 under-detected lesion and 14/24 (58%) were widely under-detected. On multivariate analysis, only solitary site of preoperative disease was associated with increased levels of under-detection of invasive disease (OR = 4.161, 95% CI, 1.368-12.657). Conclusion: Our study shows a stark discordance between preoperative and postoperative localization of bladder tumors. From a clinical perspective, incomplete localization of all sites of disease within the bladder

  14. Targeted therapies in the management of metastatic bladder cancer

    PubMed Central

    Fassan, Matteo; Trabulsi, Edouard J; Gomella, Leonard G; Baffa, Raffaele

    2007-01-01

    The management of metastatic urothelial carcinoma (UC) of the bladder is a common and complex clinical challenge. Despite the fact that UC is one of the most frequent tumors in the population, long term survival for metastatic disease remains low, and chemotherapy is curative for only a small minority of patients. UC is genetically heterogeneous, and it is surrounded by a complex tissue microenvironment. The problems of clinical practice in the field of metastatic bladder cancer have begun to stimulate translational research. Advances in the understanding of the molecular biology of urothelial cancer continue to contribute to the identification of molecular pathways upon which new therapeutic approaches can be targeted. New agents and strategies have recently been developed which can direct the most appropriate choice of treatment for advanced disease. A review of literature published on the targeted therapy for metastatic bladder cancer is presented, focusing on the molecular pathways shut down by the new therapeutic agents. PMID:19707309

  15. Immunological Basis in the Pathogenesis and Treatment of Bladder Cancer

    PubMed Central

    Thompson, David B.; Siref, Larry E.; Feloney, Michael P.; Hauke, Ralph J.; Agrawal, Devendra K.

    2015-01-01

    The pathogenesis and transition of normal urothelium into bladder carcinoma are multifactorial processes. Chronic inflammation causes initiation and progression of the underlying pathophysiology of invasive and metastatic cancer. A dichotomy is observed in the role of immune cells in bladder cancer. While the immune response defends the host by suppressing neoplastic growth, several immune cells, including neutrophils, macrophages, and T-lymphocytes, promote tumor development and progression. The levels of human neutrophil peptide-1, -2, and -3, produced by neutrophils, increase in bladder cancer and might promote tumor angiogenesis and growth. The effect of macrophages is primarily mediated by pro-inflammatory cytokines, IL-6 and TNF-α. Additionally, the underlying immunological mechanisms of two treatments, BCG and cytokine gene-modified tumor vaccines, and future directions are critically discussed. PMID:25391391

  16. 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.

  17. Statistical consideration for clinical biomarker research in bladder cancer

    PubMed Central

    Shariat, Shahrokh F.; Lotan, Yair; Vickers, Andrew; Karakiewicz, Pierre I.; Schmitz-Dräger, Bernd J.; Goebell, Peter J.; Malats, Nuria

    2012-01-01

    Purpose To critically review and illustrate current methodologic and statistical considerations for bladder cancer biomarker discovery and evaluation. Methods Original, review, and methodological articles, and editorials were reviewed and summarized. Results Biomarkers may be useful at multiple stages of bladder cancer management: early detection, diagnosis, staging, prognosis, and treatment; however, few novel biomarkers are currently used in clinical practice. The reasons for this disjunction are manifold and reflect the long and difficult pathway from candidate biomarker discovery to clinical assay, and the lack of coherent and comprehensive processes (pipelines) for biomarker development. Conceptually, the development of new biomarkers should be a process that is similar to therapeutic drug evaluation - a highly regulated process with carefully regulated phases from discovery to human applications. In a further effort to address the pervasive problem of inadequacies in the design, analysis, and reporting of biomarker prognostic studies, a set of reporting recommendations are discussed. For example, biomarkers should provide unique information that adds to known clinical and pathologic information. Conventional multivariable analyses are not sufficient to demonstrate improved prediction of outcomes. Predictive models, including or excluding any new putative biomarker, needs to show clinically significant improvement of performance in order to claim any real benefit. Towards this end, proper model building, avoidance of overfitting, and external validation are crucial. In addition, it is important to choose appropriate performance measures dependent on outcome and prediction type and to avoid use of cut-points. Biomarkers providing a continuous score provide potentially more useful information than cut-points since risk fits a continuum model. Combination of complementary and independent biomarkers is likely to better capture the biologic potential of a tumor

  18. Comparing RECIST with EORTC criteria in metastatic bladder cancer.

    PubMed

    Öztürk, Hakan

    2016-01-01

    To compare RECIST and EORTC criteria in an evaluation of response to therapy in metastatic bladder cancer and to assess their influence on decisions to administer additional therapy. A total of 42 untreated patients (38 male, 4 female) with metastatic bladder cancer were included in the study, which took place between July 2007 and April 2013. The mean age was 66.1 ± 9.93 years (range 41-84 years). A total of 144 metastatic foci were evaluated using multislice CT and (18)FDG-PET/CT before and after first-line chemotherapy. The locations, sizes, numbers and SUV(max) of the metastatic foci before and after chemotherapy were recorded, and the response to therapy was evaluated separately using RECIST and EORTC criteria, after which a statistical comparison was made. According to the RECIST and EORTC criteria, the rate of complete remission (CR) was 9.5 and 16.6 %, the rate of partial remission (PR) was 28.6 and 40.5 %, the rate of stable disease (SD) was 23.8 and 14.3 %, and the rate of progressive disease (PD) was 31.0 and 28.6 %, respectively. The overall response rate (ORR) was 38.1 versus 57.1 %, respectively, and there were no differences between the two criteria in terms of their detection of progressive disease. The rate of SD was higher with RECIST criteria; however, the difference between the two criteria was not significant in terms of PR and CR. A group of patients that had been determined as having a SD according to RECIST criteria were grouped as PR and/or CR according to EORTC criteria. Additional chemotherapy protocols can be used in second-line chemotherapy and/or cisplatin-resistant patients, according to RECIST criteria. In evaluating the response to first-line chemotherapy for metastatic bladder cancer, EORTC criteria, using (18)FDG-PET/CT scans, can be considered as a more applicable and accurate diagnostic tool. The anatomical findings obtained through imaging methods and from functional/metabolic data obtained by PET/CT can be useful in the

  19. Trimodality therapy in bladder cancer: Who, what and when?

    PubMed Central

    Premo, Christopher; Apolo, Andrea B.; Agarwal, Piyush K.

    2015-01-01

    Summary Radical cystectomy is a standard treatment for non-metastatic, muscle-invasive bladder cancer. Treatment with trimodality therapy consisting of maximal transurethral resection of the bladder tumor (TURBT) followed by concurrent chemotherapy and radiation has emerged as a method to preserve the native bladder in highly motivated patients. A number of factors can impact the likelihood of long term bladder preservation after trimodality therapy, and therefore should be taken into account when selecting patients. New radiation techniques such as intensity modulated radiation therapy and image guided radiation therapy may decrease the toxicity of radiotherapy in this setting, but remain an area of active study. Novel chemotherapy regimens may improve response rates and minimize toxicity. PMID:25882559

  20. The West Midlands Bladder Cancer Prognosis Programme: rationale and design.

    PubMed

    Zeegers, Maurice P; Bryan, Richard T; Langford, Carolyn; Billingham, Lucinda; Murray, Paul; Deshmukh, Neeta S; Hussain, Syed; James, Nick; Wallace, D Michael A; Cheng, K K

    2010-03-01

    OBJECTIVE To describe the rationale and design of the Bladder Cancer Prognosis Programme (BCPP), and to demonstrate the capability of this design. METHODS There is a need to understand the determinants of bladder cancer to help reduce recurrence, progression, morbidity, mortality and related costs. We previously showed that lifestyle factors are important for determining the risk of bladder cancer, but little is known about their importance in determining the risk of recurrence or progression after diagnosis. Also, histopathological factors alone provide only crude prognostication; the analysis of molecular markers represents a method for refinement but research in this area has not been useful in informing therapeutic decisions or prognostication. The BCPP is a prospective longitudinal cohort study of all patients with newly diagnosed bladder cancer within the West Midlands (UK), investigating the influence of lifestyle factors on recurrence and progression, health-related quality of life, the predictive effect of a panel of molecular markers on recurrence or progression, and the establishment of Europe's largest comprehensive bladder cancer bio-repository. It also incorporates the first randomized clinical trial on the efficacy of selenium and vitamin E on bladder cancer. The numbers and proportions of eligible patients recruited, questionnaires completed and specimens obtained were all recorded. RESULTS Since December 2005, 771 patients have been recruited (68% of eligible patients) and of these, 331 are currently being followed up by questionnaires. We have obtained blood, urine and tumour tissues from 92%, 80% and 80% of patients, respectively. CONCLUSIONS The design of the BCPP has allowed this study to be incorporated into routine clinical work throughout the West Midlands, achieving high levels of recruitment, and data and specimen collection. This might represent a model for the future investigation of urological and other malignancies.

  1. Preclinical dosimetry of magnetic fluid hyperthermia for bladder cancer

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

    Background Despite positive efficacy, thermotherapy is not widely used in clinical oncology. Difficulties associated with field penetration and controlling power deposition patterns in heterogeneous tissue have limited its use for heating deep in the body. Heat generation using iron-oxide super-paramagnetic nanoparticles excited with magnetic fields has been demonstrated to overcome some of these limitations. The objective of this preclinical study is to investigate the feasibility of treating bladder cancer with magnetic fluid hyperthermia (MFH) by analyzing the thermal dosimetry of nanoparticle heating in a rat bladder model. Methods The bladders of 25 female rats were injected with 0.4 ml of Actium Biosystems magnetite-based nanoparticles (Actium Biosystems, Boulder CO) via catheters inserted in the urethra. To assess the distribution of nanoparticles in the rat after injection we used the 7 T small animal MRI system (Bruker ClinScan, Bruker BioSpin MRI GmbH, Ettlingen, Germany). Heat treatments were performed with a small animal magnetic field applicator (Actium Biosystems, Boulder CO) with a goal of raising bladder temperature to 42°C in <10min and maintaining for 60min. Temperatures were measured throughout the rat with seven fiberoptic temperature probes (OpSens Technologies, Quebec Canada) to characterize our ability to localize heat within the bladder target. Results The MRI study confirms the effectiveness of the catheterization procedure to homogenously distribute nanoparticles throughout the bladder. Thermal dosimetry data demonstrate our ability to controllably raise temperature of rat bladder >1°C/min to a steady-state of 42°C. Conclusion Our data demonstrate that a MFH system provides well-localized heating of rat bladder with effective control of temperature in the bladder and minimal heating of surrounding tissues.

  2. Preclinical Dosimetry of Magnetic Fluid Hyperthermia for Bladder Cancer.

    PubMed

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

    2013-02-26

    Despite positive efficacy, thermotherapy is not widely used in clinical oncology. Difficulties associated with field penetration and controlling power deposition patterns in heterogeneous tissue have limited its use for heating deep in the body. Heat generation using iron-oxide super-paramagnetic nanoparticles excited with magnetic fields has been demonstrated to overcome some of these limitations. The objective of this preclinical study is to investigate the feasibility of treating bladder cancer with magnetic fluid hyperthermia (MFH) by analyzing the thermal dosimetry of nanoparticle heating in a rat bladder model. The bladders of 25 female rats were injected with 0.4 ml of Actium Biosystems magnetite-based nanoparticles (Actium Biosystems, Boulder CO) via catheters inserted in the urethra. To assess the distribution of nanoparticles in the rat after injection we used the 7 T small animal MRI system (Bruker ClinScan, Bruker BioSpin MRI GmbH, Ettlingen, Germany). Heat treatments were performed with a small animal magnetic field applicator (Actium Biosystems, Boulder CO) with a goal of raising bladder temperature to 42°C in <10min and maintaining for 60min. Temperatures were measured throughout the rat with seven fiberoptic temperature probes (OpSens Technologies, Quebec Canada) to characterize our ability to localize heat within the bladder target. The MRI study confirms the effectiveness of the catheterization procedure to homogenously distribute nanoparticles throughout the bladder. Thermal dosimetry data demonstrate our ability to controllably raise temperature of rat bladder ≥1°C/min to a steady-state of 42°C. Our data demonstrate that a MFH system provides well-localized heating of rat bladder with effective control of temperature in the bladder and minimal heating of surrounding tissues.

  3. Bladder injury secondary to obturator reflex is more common with plasmakinetic transurethral resection than monopolar transurethral resection of bladder cancer

    PubMed Central

    Ozer, Kutan; Gorgel, Sacit Nuri; Ozbek, Emin

    2015-01-01

    Introduction Transurethral resection (TUR) is the most common surgical technique for the diagnosis and initial treatment of bladder cancer. In this study, we evaluated two surgical techniques in terms of bladder injury due to obturator reflex in patients that underwent TUR for non-muscle invasive bladder cancer (NMIBC). Material and methods 93 patients who underwent TUR for bladder cancer were analyzed. Fifty patients underwent monopolar resection and 43 patients underwent plasmakinetic resection. Standard TUR were performed with conventional Storz monopolar resection using a U-shaped cutting loop, 120V cutting/80 V coagulation settings, 5% mannitol fluid was used for irrigation. For bipolar resection, an Olympus ESG-400 plasmakinetic loop bipolar device using a U-shaped cutting loop, 160V cutting/80V coagulation settings and normal saline for irrigation was used. Results In the monopolar resection group; obturator reflex was seen in 4 (8%) patients. Bladder perforation caused by the obturator reflex was seen in 4 (8%) patients, but hemorrhage and other major complications were not seen in this group. In the bipolar resection group; obturator reflex was seen in 15 (34%) patients. Bladder perforation caused by the obturator reflex was seen in 10 (23%) patients. Conclusions Bipolar transurethral resection of bladder tumor was not superior to monopolar resection with respect to obturator reflex and bladder perforation. We conclude that we do not yet have enough experience concerning the long-term complications and major complications associated with bipolar resection of bladder cancer. PMID:26568867

  4. Why is perioperative chemotherapy for bladder cancer underutilized?

    PubMed

    Patafio, Francis M; Mackillop, William J; Feldman-Stewart, Deb; Siemens, David Robert; Booth, Christopher M

    2014-05-01

    Despite clinical evidence and recommendations from international treatment guidelines, the use of perioperative chemotherapy for muscle-invasive bladder cancer in routine practice remains low. Although multiple studies have described underutilization, there is an urgent need to better understand the elements contributing to the observed gaps in care. In this commentary, we explore what is known about the factors contributing to underutilization of perioperative chemotherapy for muscle-invasive bladder cancer. We also propose a framework to guide future knowledge translation activities in an effort to improve the care and outcomes of patients with this disease.

  5. Nonmuscle invasive bladder cancer: a primer on immunotherapy

    PubMed Central

    Maruf, Mahir; Brancato, Sam J.; Agarwal, Piyush K.

    2016-01-01

    Intravesical Bacillus Calmette-Guérin (BCG) has long been the gold standard treatment of nonmuscle invasive bladder cancer. Recently, there has been an emergence of novel immunotherapeutic agents, which have shown promise in the treatment of urothelial cell carcinoma. These agents aim to augment, modify, or enhance the immune response. Such strategies include recombinant BCG, monoclonal antibodies, vaccines, gene therapy, and adoptive T-cell therapy. Here, we review the emerging immunotherapeutics in the treatment of nonmuscle invasive bladder cancer. PMID:27458527

  6. [New approaches for the treatment of superficial bladder cancer].

    PubMed

    Sager, Caroline Carera; Benamran, Daniel A; Wirth, Gregory; Iselin, Christophe E

    2015-12-02

    Extending up to the submucosa, superficial bladder tumours (pTis, pTa et pTi) are initially treated by transurethral resection. According to their risk of recurrence and progression, this frequent cancer subsequently benefits from intra-vesical instillations of cytotoxic agents and immunomodulators. Several new treatments are currently being evaluated, namely new genetically modified BCG strains, so as novel means to administrate intravesical chemotherapy, which seam to improve prognosis. Owing to the significant prevalence of superficial bladder cancer and its morbidity, these new therapeutic means will probably be increasingly used.

  7. Urine and bladder washing cytology for detection of urothelial carcinoma: standard test with new possibilities

    PubMed Central

    Flezar, Margareta Strojan

    2010-01-01

    Background Light microscopic evaluation of cell morphology in preparations from urine or bladder washing containing exfoliated cells is a standard and primary method for the detection of bladder cancer and also malignancy from other parts of the urinary tract. The cytopathologic examination is a valuable method to detect an early recurrence of malignancy or new primary carcinoma during the follow-up of patients after the treatment of bladder cancer. Conclusions Characteristic cellular and nuclear signs of malignancy indicate invasive or in situ urothelial carcinoma or high-grade papillary urothelial carcinoma. However, low sensitivity of the method reflects the unreliable cytopathologic diagnosis of low-grade urothelial neoplasms as cellular and nuclear signs of malignancy in these neoplasms are poorly manifested. Many different markers were developed to improve the diagnosis of bladder carcinoma on urinary samples. UroVysion™ test is among the newest and most promising tests. By the method of in situ hybridization one can detect specific cytogenetic changes of urothelial carcinoma. PMID:22933917

  8. Serum vitamin D and risk of bladder cancer.

    PubMed

    Mondul, Alison M; Weinstein, Stephanie J; Männistö, Satu; Snyder, Kirk; Horst, Ronald L; Virtamo, Jarmo; Albanes, Demetrius

    2010-11-15

    Vitamin D may protect against several cancers, but data about the association between circulating vitamin D and bladder cancer are limited. Within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a randomized controlled trial conducted to determine the effects of α-tocopherol and β-carotene supplements on cancer incidence in male smokers, 250 bladder cancer cases were randomly sampled by month of blood collection. Controls were matched 1:1 to cases on age at randomization and date of blood collection. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of bladder cancer by a priori categories of baseline serum 25-hydroxyvitamin D [25(OH)D; i.e., <25, 25 to <37.5, 37.5 to <50, ≥50 nmol/L] and by season-specific quartiles. After multivariable adjustment, we found that lower 25(OH)D was associated with a statistically significantly increased risk of bladder cancer (versus ≥50 nmol/L; <25 nmol/L: OR, 1.73; 95% CI, 1.03-2.91; 25 to <37.5 nmol/L: OR, 1.81; 95% CI, 1.05-3.14; 37.5 to <50 nmol/L: OR, 1.76; 95% CI, 1.02-3.02; P trend=0.04). Similarly, increased risks for the lowest vitamin D category were observed when season-specific quartiles were used (Q1 versus Q4: OR, 1.63; 95% CI, 0.96-2.75; P trend=0.03). In this prospective study of male smokers, lower serum 25(OH)D was associated with an increased risk of bladder cancer. Future studies should examine the association in other populations, especially nonsmokers and women. Copyright © 2010 AACR.

  9. The C228T mutation of TERT promoter frequently occurs in bladder cancer stem cells and contributes to tumorigenesis of bladder cancer

    PubMed Central

    Du, Ying; He, Luyun; Cai, Zhiming; Wang, Jiansong; Fan, Zusen

    2015-01-01

    Bladder cancer is one of the most common malignant tumors worldwide. Bladder cancer stem cells (BCSCs) have been isolated recently but have not been defined yet. Here we sorted BCSCs from bladder tumor tissues or normal bladder stem cells (NBBCs) from adjacent normal bladder tissues. We found that the C228T mutation (chr5, 1, 295, 228 C > T) of TERT promoter frequently occurs in BCSCs, but not exist in NBBCs. Importantly, introducing the C228T mutation in NBBCs causes TERT overexpression and transformation of bladder cancer. Restoration of the C228T mutation to T228C in BCSCs can recover the TERT expression to a basal level and abolish tumor formation. Additionally, the C228T mutation of TERT promoter triggers TERT expression leading to increased telomerase activity. TERT expression levels are consistent with clinical severity and prognosis of bladder cancer. PMID:26143634

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

    PubMed

    Kapoor, Vinay K

    2015-07-27

    Gall bladder cancer (GBC) has one of the poorest outcomes of all cancers. Early GBC is difficult to diagnose on even computed tomography. GB has no submucosa and the cancer infiltrates directly into the muscularis propria. GB wall is thin and important adjacent organs viz. liver, duodenum and pancreas get easily infiltrated. Tumor in the GB neck often needs extended right hepatectomy. Infiltration of duodenum/pancreas may necessitate pancreato-duodenectomy or even hepato-pancreato-duodenectomy. Mortality of surgical procedures, when performed for GBC, is higher than when performed for other cancers. Survival in GBC, even after R0 resection, is poor. There is no proven role of neo-adjuvant or adjuvant therapy for loco-regionally advanced GBC. There is no role of palliative surgery in metastatic GBC. Early GBC is diagnosed incidentally after cholecystectomy for stones and requires reoperation for completion extended cholecystectomy but unfortunately, most surgeons are not aware of this. GBC has a peculiar epidemiology and is uncommon in the West and has, therefore, not received much attention. Preventive cholecystectomy for asymptomatic stones is not recommended and there is no serum marker for screening. With all factors pitched against it, it does appear that GBC is a bad cancer per se!

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

    PubMed Central

    Kapoor, Vinay K

    2015-01-01

    Gall bladder cancer (GBC) has one of the poorest outcomes of all cancers. Early GBC is difficult to diagnose on even computed tomography. GB has no submucosa and the cancer infiltrates directly into the muscularis propria. GB wall is thin and important adjacent organs viz. liver, duodenum and pancreas get easily infiltrated. Tumor in the GB neck often needs extended right hepatectomy. Infiltration of duodenum/pancreas may necessitate pancreato-duodenectomy or even hepato-pancreato-duodenectomy. Mortality of surgical procedures, when performed for GBC, is higher than when performed for other cancers. Survival in GBC, even after R0 resection, is poor. There is no proven role of neo-adjuvant or adjuvant therapy for loco-regionally advanced GBC. There is no role of palliative surgery in metastatic GBC. Early GBC is diagnosed incidentally after cholecystectomy for stones and requires reoperation for completion extended cholecystectomy but unfortunately, most surgeons are not aware of this. GBC has a peculiar epidemiology and is uncommon in the West and has, therefore, not received much attention. Preventive cholecystectomy for asymptomatic stones is not recommended and there is no serum marker for screening. With all factors pitched against it, it does appear that GBC is a bad cancer per se! PMID:26225192

  12. 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

  13. Insight into the molecular basis of Schistosoma haematobium-induced bladder cancer through urine proteomics.

    PubMed

    Bernardo, Carina; Cunha, Maria Cláudia; Santos, Júlio Henrique; da Costa, José M Correia; Brindley, Paul J; Lopes, Carlos; Amado, Francisco; Ferreira, Rita; Vitorino, Rui; Santos, Lúcio Lara

    2016-08-01

    Infection due to Schistosoma haematobium is carcinogenic. However, the cellular and molecular mechanisms underlying urogenital schistosomiasis (UGS)-induced carcinogenesis have not been well defined. Conceptually, early molecular detection of this phenomenon, through non-invasive procedures, seems feasible and is desirable. Previous analysis of urine collected during UGS suggests that estrogen metabolites, including depurinating adducts, may be useful for this purpose. Here, a new direction was pursued: the identification of molecular pathways and potential biomarkers in S. haematobium-induced bladder cancer by analyzing the proteome profiling of urine samples from UGS patients. GeLC-MS/MS followed by protein-protein interaction analysis indicated oxidative stress and immune defense systems responsible for microbicide activity are the most representative clusters in UGS patients. Proteins involved in immunity, negative regulation of endopeptidase activity, and inflammation were more prevalent in UGS patients with bladder cancer, whereas proteins with roles in renal system process, sensory perception, and gas and oxygen transport were more abundant in subjects with urothelial carcinoma not associated with UGS. These findings highlighted a Th2-type immune response induced by S. haematobium, which seems to be further modulated by tumorigenesis, resulting in high-grade bladder cancer characterized by an inflammatory response and complement activation alternative pathway. These findings established a starting point for the development of multimarker strategies for the early detection of UGS-induced bladder cancer.

  14. Physical activity in the prevention and management of bladder cancer.

    PubMed

    Shephard, Roy J

    2017-10-01

    The aim was to examine the role of physical activity in reducing the risk of bladder cancer, and in managing established disease. A systematic search of Ovid/Medline from 1996 to June 2016 coupled the term urinary bladder neoplasms (25,061 hits) with markers of physical activity (exercise, physical activity, physical education/training, athletes, and physical fitness, a total of 246,683 unique entries). Of 42 titles identified, 18 relevant abstracts were supplemented by reviewing reference lists and personal files to yield 21 articles on prevention of bladder cancer, and 8 on physical activity in disease management. Three cohort and 3 case-control studies examined occupational activity. One report found a statistically significant 40% increase in bladder cancers with a sedentary job, and 2 of 5 other reports found a non-significant trend to decreased risk with physically demanding work. Of 9 cohort and 2 case-control leisure analyses, 1 found significant benefit from physical activity, and 6 others trended to a 11-34% reduction of risk, with adverse effects in only 2 studies. After development of bladder cancer, physical activity was commonly low. However, greater physical activity decreased the risks of cystectomy and increased the quality of life following surgery. Better categorization of lifetime activity and fuller allowance for co-variates seems needed to establish conclusively that greater habitual physical activity will reduce the risk of bladder cancer. Nevertheless, an active lifestyle should be encouraged pending definitive information, because of positive trends and the more general health advantages of regular exercise.

  15. Computer-aided detection of bladder mass within contrast-enhanced region of CTU

    NASA Astrophysics Data System (ADS)

    Cha, Kenny; Hadjiiski, Lubomir; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Zhou, Chuan

    2015-03-01

    We are developing a computer-aided detection system for bladder cancer on CTU. The bladder was automatically segmented with our Conjoint Level set Analysis and Segmentation System (CLASS). In this preliminary study, we developed a system for detecting mass within the contrast-enhanced (C) region of the bladder. The C region was delineated from the segmented bladders using a method based on maximum intensity projection. The bladder wall of the C region was extracted using thresholding to remove the contrast material. The wall on each slice was transformed into a wall profile. Morphology and voxel intensity along the profile were analyzed and suspicious locations were labeled as lesion candidates. The candidates were segmented and 20 morphological features were extracted from each candidate. A data set of 35 patients with 45 biopsy-proven bladder lesions within the C region was used for system evaluation. Stepwise feature selection with simplex optimization and leave-one-case-out method was used for training and validation. For each partition in the leave-one-case-out method, features were selected from the training cases and a linear discriminant (LDA) classifier was designed to merge the selected features into a single score for classification of the lesion candidates into bladder lesions and normal findings in the left-out case. A single score was generated for each lesion candidate. The performance of the CAD system was evaluated by FROC analysis. At an FP rate of 2.5 FPs/case, the system achieved a sensitivity of 82%, while at 1.7 FPs/case, a sensitivity of 71%.

  16. 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

  17. Unusual presentation of metastatic gall bladder cancer.

    PubMed

    Shukla, Piyush; Roy, Soumyajit; Tiwari, Vivek; Mohanti, Bidhu K

    2014-01-01

    To report the first case of rare isolated breast metastasis from carcinoma gall bladder. Single patient case report. A 35-year-old pre-menopausal female presented with 2 * 2 cm right upper outer quadrant breast lump. Post-mastectomy, histology confirmed it to be metastatic adenocarcinoma positive for both Cytokeratin (CK) 7 and CK20. Past history as told by the patient revealed that 2 years back, cholecystectomy was performed for gall stones, of which no histology reports were present; she had a port site scar recurrence which showed it to be adenocarcinoma. Adjuvant chemotherapy and radiotherapy was advised which the patient did not complete. This is probably the first case reported of isolated breast metastasis from gall bladder carcinoma, diagnosed retrospectively. It also highlights the importance of adjuvant treatment in gall bladder malignancy.

  18. ATM participates in the regulation of viability and cell cycle via ellipticine in bladder cancer

    PubMed Central

    Tao, Shuixiang; Meng, Shuai; Zheng, Xiangyi; Xie, Liping

    2017-01-01

    Ellipticine, an alkaloid isolated from Apocyanaceae plants, has been demonstrated to exhibit antitumor activity in several cancers. However, the effect and the mechanisms underlying its action have not been investigated in human bladder cancer cells. The aim of the present study was to investigate the effect and mechanism of ellipticine on the behavior of T-24 bladder cancer cells. T-24 cells were treated with varying concentrations and durations of ellipticine. Cell viability was evaluated by Cell Counting Kit-8 assay. Cell motility was analyzed by Transwell migration assay. Flow cytometry, reverse transcription-quantitative polymerase chain reaction and western blot analyses were performed to detect the cell cycle and signaling pathways involved. The results demonstrated that ellipticine suppressed proliferation and inhibited the migration ability of T-24 bladder cancer cells in a dose- and time-dependent manner, and resulted in G2/M cell cycle arrest. The mechanism of this action was demonstrated to be due to ellipticine-triggered activation of the ATM serine/threonine kinase pathway. These data therefore suggest that ellipticine may be effective towards treating human bladder cancer. PMID:28138703

  19. The natural history of bladder cancer. Implications for therapy.

    PubMed

    Lee, R; Droller, M J

    2000-02-01

    Transitional cell carcinoma of the bladder is comprised of a variety of cancer diatheses that manifest a spectrum of distinct biologic potentials. Although these diseases have traditionally been classified as "superficial" and "muscle invasive" on the basis of their histologic appearance (depth of penetration of the "bladder wall" and corresponding prognosis) the pathways presumably followed by the various forms of these cancers imply an even greater complexity. These disparate pathways may reflect different events in carcinogenesis, which may determine subsequent development and risk for either recurrence or progression. In addition, biologic activity and malignant potential for each type of cancer may be associated with distinctive molecular and genetic alterations. These considerations may provide an opportunity to expand traditional staging systems in creating molecular profiles that may more precisely characterize the biologic potential of these tumor diatheses. Although there are far more questions than answers concerning how these alterations may effect the natural history of bladder cancer, molecular-based identification of bladder cancer patients at greatest risk for progression may ultimately improve clinical management.

  20. Bladder cancer in Native Americans and Alaskan Natives.

    PubMed

    Watson, Richard A; Sidor, Monika

    2008-07-01

    The prevalence of bladder cancer among Native Americans/Alaskan Natives (NAs/ANs) is generally considered to be low. However, the relative morbidity and mortality seem high. We have undertaken this survey of the published data to explore and document this observation. An extensive survey of the published data was undertaken. The Surveillance, Epidemiology and End Results data in particular were assessed. The incidence of bladder cancer among the NA/AN peoples is inexplicably low. This low incidence is more remarkable, given the widespread use of tobacco products and the disproportionately high incidence of kidney cancer in this same population. Despite this low incidence, NA/AN men and women seem to be at a relatively greater risk of dying of bladder cancer, once it has been diagnosed. More and larger studies are needed to clarify and update the incidence, cell type, and clinical outcomes of bladder cancer among NA/AN men and women. Social, economic, and political barriers to treatment also need to be addressed. Effective steps need to be undertaken to ensure more timely diagnosis and treatment of this disease.

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

    PubMed Central

    Chiu, Melody; McBeth, Lucien; Sindhwani, Puneet

    2017-01-01

    The use of thiazolidinedione (TZD) therapy in type II diabetic patients has proven useful in the lowering of blood glucose levels. However, recent investigations have shown that there may be potential health concerns associated, including the risk of developing bladder cancer as well as complications in the cardiovasculature. TZDs are ligands for the nuclear receptor PPARγ, and activation causes lipid uptake and insulin sensitization, both of which are critical processes for diabetic patients whose bodies are unable to utilize insulin effectively. Several studies have shown that PPARγ/TZDs decrease IGF-1 levels and, thus, reduce cancer growth in carcinomas such as the pancreas, colon, liver, and prostate. However, other studies have shed light on the potential of the receptor as a biomarker for uroepithelial carcinomas, particularly due to its stimulatory effect on migration of bladder cancer cells. Furthermore, PPARγ may provide the tumor-promoting microenvironment by de novo synthesis of nutrients that are needed for bladder cancer development. In this review, we closely examine the TZD class of drugs and their effects on PPARγ in patient studies along with additional molecular factors that are positive modulators, such as protein phosphatase 5 (PP5), which may have considerable implications for bladder cancer therapy. PMID:28348577

  2. Urinary APE1/Ref-1: A Potential Bladder Cancer Biomarker.

    PubMed

    Choi, Sunga; Shin, Ju Hyun; Lee, Yu Ran; Joo, Hee Kyoung; Song, Ki Hak; Na, Yong Gil; Chang, Seok Jong; Lim, Jae Sung; Jeon, Byeong Hwa

    2016-01-01

    Bladder cancer (BCa) is one of the most common urothelial cancers with still noticeable incidence rate. Early detection of BCa is highly correlated with successful therapeutic outcomes. We previously showed that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) was expressed at an increased level in the serum of BCa patients when compared to the level in healthy controls. In this study, we investigated whether urinary APE1/Ref-1 was also elevated in patients with BCa. In this case-control study, voided urine was collected from 277 subjects including 169 BCa patients and 108 non-BCa controls. Urinary APE1/Ref-1 level was assessed by enzyme-linked immunosorbent assay (ELISA). APE1/Ref-1 levels were significantly elevated in BCa patients relative to levels in non-BCa controls and were correlated with tumor grade and stage. Urinary APE1/Ref-1 levels were also higher in patients with recurrence history of BCa. The receiver operating characteristics (ROC) curve of APE1/Ref-1 showed an area under the curve of 0.83, indicating the reliability and validity of this biomarker. The optimal combination of sensitivity and specificity was determined to be 82% and 80% at a cut-off value of 0.376 ng/100 μL for detection of APE1/Ref-1 in urine. In conclusion, urinary APE1/Ref-1 levels measured from noninvasively obtained body fluids would be clinically applicable for diagnosis of BCa.

  3. 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.

  4. MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1.

    PubMed

    Li, Peng; Yang, Xiao; Cheng, Yidong; Zhang, Xiaolei; Yang, Chengdi; Deng, Xiaheng; Li, Pengchao; Tao, Jun; Yang, Haiwei; Wei, Jifu; Tang, Jingyuan; Yuan, Wenbo; Lu, Qiang; Xu, Xiaoting; Gu, Min

    2017-01-01

    MicroRNA-218 (miR-218) is down-regulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. However, the involvement of miR-218 in chemo-sensitivity to cisplatin and the precise mechanism of this action remained unknown in bladder cancer. qRT-PCR was used to detect miR-218 and its target Glut1 expression in bladder cancer cell lines T24 and EJ. CCK-8 method was utilized to measure the cell viability. IC 50 was calculated via a probit regression model. Glut1 was detected by western blotting for analysis of potential mechanism. Luciferase reporter assay was utilized to validate Glut1 as a direct target gene of miR-218. The intracellular level of GSH and ROS were determined using a commercial colorimetric assay kit and 2', 7'-dichlorodihydro-fluorescein diacetate, respectively. Over-expression of miR-218 significantly reduced the rate of glucose uptake and total level of GSH and enhanced the chemo-sensitivity of bladder cancer to cisplatin. Mechanistically, Glut1 was found to be a direct and functional target of miR-218. Up-regulation of Glut1 could restore chemo-resistance in T24 and EJ cells. On the contrary, knockdown of Glut1 could generate a similar effect as up-regulating the expression of miR-218. MiR-218 increases the sensitivity of bladder cancer to cisplatin by targeting Glut1. Restoration of miR-218 and repression of glut1 may provide a potential strategy to restore chemo-sensitivity in bladder cancer. © 2017 The Author(s)Published by S. Karger AG, Basel.

  5. 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.

  6. Urine cytology in the detection of bladder tumor recurrence.

    PubMed

    Orandi, A; Orandi, M

    1976-11-01

    Of 118 patients with primary bladder tumors seen since 1966, 73 have been followed with urine cytology since 1969. Of the 406 tests there have been 85 positive, 296 negative and 25 ambiguous reports. The incidence of falsely positive results is estimated at 4% but the incidence of falsely negative results cannot be assessed in this study. Currently, 51 patients are living, 2 of whom had been seen in 1966. Of the 51 patients 43 are being followed with urine cytology. Bimonthly urine cytology has been found to be a relaible, convenient, safe, less hazardous and less costly method for the detection of bladder tumor recurrence.

  7. 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

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

    PubMed

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

    2014-03-01

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

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

    SciTech Connect

    Bingsong Lei; Xiaoyuan Deng; Huajiang Wei; Zhouyi Guo; Guoyong Wu; Hongqin Yang; Shusen Xie; Yonghong He

    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{sup -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)

  10. Chemotherapeutic potential of quercetin on human bladder cancer cells.

    PubMed

    Oršolić, Nada; Karač, Ivo; Sirovina, Damir; Kukolj, Marina; Kunštić, Martina; Gajski, Goran; Garaj-Vrhovac, Vera; Štajcar, Damir

    2016-07-28

    In an effort to improve local bladder cancer control, we investigated the cytotoxic and genotoxic effects of quercetin on human bladder cancer T24 cells. The cytotoxic effect of quercetin against T24 cells was examined by MTT test, clonogenic assay as well as DNA damaging effect by comet assay. In addition, the cytotoxic effect of quercetin on the primary culture of papillary urothelial carcinoma (PUC), histopathological stage T1 of low- or high-grade tumours, was investigated. Our analysis demonstrated a high correlation between reduced number of colony and cell viability and an increase in DNA damage of T24 cells incubated with quercetin at doses of 1 and 50 µM during short term incubation (2 h). At all exposure times (24, 48 and 72 h), the efficacy of quercetin, administered at a 10× higher dose compared to T24 cells, was statistically significant (P < 0.05) for the primary culture of PUC. In conclusion, our study suggests that quercetin could inhibit cell proliferation and colony formation of human bladder cancer cells by inducing DNA damage and that quercetin may be an effective chemopreventive and chemotherapeutic agent for papillary urothelial bladder cancer after transurethral resection.

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

    PubMed

    Whitmore, W F; Batata, M

    1984-11-01

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

  12. AB266. Expression of long noncoding RNA lncRNA-n336928 is correlated with tumor stage and grade and overall survival in bladder cancer

    PubMed Central

    Chen, Tao; Wu, Changli; Hu, Hailong

    2016-01-01

    Background Long noncoding RNAs (lncRNAs) have been implicated playing important roles in human urologic cancers. Up to date, quite a few lncRNAs have been implicated as promising biomarkers for tumor early detection and prognosis monitoring. Methods In the present study, microarray analysis was initially performed to screen the differentially expressed lncRNAs between bladder cancer tissues and paired adjacent non-cancerous tissues (n=3).Subsequent qRT-PCR validation was conducted using tissue samples from 95 patients with bladder cancer. Results Results showed that the expression level of lncRNA-n336928 (noncode database ID: n336928) was significantly higher in bladder cancer tissues compared to that in adjacent noncancerous tissues (P<0.001). Chi-square test showed that expression of lncRNA-n336928 was positively correlated with bladder tumor stage and histological grade (P<0.001). Kaplan-Meier survival analysis revealed that patients with bladder cancer with high expression of lncRNA-n336928 had shorter overall survival time compared to patients with low expression of lncRNA-n336928. Multivariate analysis indicated that lncRNA-n336928 was an independent prognostic factor for overall survival for bladder cancer patients. Conclusions our study shows that high expression of lncRNA-n336928 is associated with the progression of bladder cancer, and that lncRNA-n336928 might serve as a biomarker for prognosis of bladder cancer

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

    PubMed Central

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

    2016-01-01

    Genome-wide association studies (GWAS) are designed to identify individual regions associated with cancer risk, but only explain a small fraction of the inherited variability. Alternative approach analyzing genetic variants within biological pathways has been proposed to discover networks of susceptibility genes with additional effects. The gene set enrichment analysis (GSEA) may complement and expand traditional GWAS analysis to identify novel genes and pathways associated with bladder cancer risk. We selected three GSEA methods: Gen-Gen, Aligator, and the SNP Ratio Test to evaluate cellular signaling pathways involved in bladder cancer susceptibility in a Texas GWAS population. The candidate genetic polymorphisms from the significant pathway selected by GSEA were validated in an independent NCI GWAS. We identified 18 novel pathways (P < 0.05) significantly associated with bladder cancer risk. Five of the most promising pathways (P ≤ 0.001 in any of the three GSEA methods) among the 18 pathways included two cell cycle pathways and neural cell adhesion molecule (NCAM), platelet-derived growth factor (PDGF), and unfolded protein response pathways. We validated the candidate polymorphisms in the NCI GWAS and found variants of RAPGEF1, SKP1, HERPUD1, CACNB2, CACNA1C, CACNA1S, COL4A2, SRC, and CACNA1C were associated with bladder cancer risk. Two CCNE1 variants, rs8102137 and rs997669, from cell cycle pathways showed the strongest associations; the CCNE1 signal at 19q12 has already been reported in previous GWAS. These findings offer additional etiologic insights highlighting the specific genes and pathways associated with bladder cancer development. GSEA may be a complementary tool to GWAS to identify additional loci of cancer susceptibility. PMID:27738493

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

    ClinicalTrials.gov

    2016-12-22

    Metastatic Ureteral Neoplasm; Metastatic Urethral Neoplasm; Stage III Bladder Urothelial Carcinoma; Stage III Ureter Cancer; Stage III Urethral Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Ureter Cancer; Stage IV Urethral Cancer; Ureter Urothelial Carcinoma; Urethral Urothelial Carcinoma

  15. Characterization and noninvasive diagnosis of bladder cancer with serum surface enhanced Raman spectroscopy and genetic algorithms

    NASA Astrophysics Data System (ADS)

    Li, Shaoxin; Li, Linfang; Zeng, Qiuyao; Zhang, Yanjiao; Guo, Zhouyi; Liu, Zhiming; Jin, Mei; Su, Chengkang; Lin, Lin; Xu, Junfa; Liu, Songhao

    2015-05-01

    This study aims to characterize and classify serum surface-enhanced Raman spectroscopy (SERS) spectra between bladder cancer patients and normal volunteers by genetic algorithms (GAs) combined with linear discriminate analysis (LDA). Two group serum SERS spectra excited with nanoparticles are collected from healthy volunteers (n = 36) and bladder cancer patients (n = 55). Six diagnostic Raman bands in the regions of 481-486, 682-687, 1018-1034, 1313-1323, 1450-1459 and 1582-1587 cm-1 related to proteins, nucleic acids and lipids are picked out with the GAs and LDA. By the diagnostic models built with the identified six Raman bands, the improved diagnostic sensitivity of 90.9% and specificity of 100% were acquired for classifying bladder cancer patients from normal serum SERS spectra. The results are superior to the sensitivity of 74.6% and specificity of 97.2% obtained with principal component analysis by the same serum SERS spectra dataset. Receiver operating characteristic (ROC) curves further confirmed the efficiency of diagnostic algorithm based on GA-LDA technique. This exploratory work demonstrates that the serum SERS associated with GA-LDA technique has enormous potential to characterize and non-invasively detect bladder cancer through peripheral blood.

  16. Pesticide exposure and risk of bladder cancer: A meta-analysis

    PubMed Central

    Xie, Bo; Zhu, Yi; Wu, Jian; Li, Shiqi; Meng, Shuai; Zheng, Xiangyi; Ji, Alin; Xie, Liping

    2016-01-01

    Objective We conducted a meta-analysis to quantitatively evaluate the correlation between pesticide exposure and the risk of bladder cancer by summarizing the results of published case-control and cohort studies. Methods A systematic literature search of articles update to February 2015 was conducted via Pubmed, Web of Science, Cochrane Library, and the Chinese National Knowledge Infrastructure (CNKI) databases, and the references of the retrieved articles. Fixed- or random-effect models were used to summarize the estimates of OR with 95% CIs for the highest versus the lowest exposure of pesticide. Results The pooled OR estimates indicated that pesticide exposure was associated with an increased risk of bladder cancer (OR=1.649, 95% CI 1.223-2.223). In subgroup analysis, we detected pesticide exposure demonstrated as a significant risk factor on bladder cancer in America (OR=1.741, 95% CI 1.270-2.388). Similar results were discovered in both case-control group and cohort group (OR=2.075, 95% CI 1.183-3.638, OR=1.146, 95% CI 1.074-1.223, respectively). No evidence of publication bias was found by Begg's or Egger's test (P = 0.210, P = 0.358, respectively). Conclusion In conclusion, our meta-analysis indicated that pesticide exposure was associated with an increased risk of bladder cancer. Further researches should be conducted to confirm the findings in our study and better clarify the potential biological mechanisms. PMID:27557494

  17. Characterization and noninvasive diagnosis of bladder cancer with serum surface enhanced Raman spectroscopy and genetic algorithms.

    PubMed

    Li, Shaoxin; Li, Linfang; Zeng, Qiuyao; Zhang, Yanjiao; Guo, Zhouyi; Liu, Zhiming; Jin, Mei; Su, Chengkang; Lin, Lin; Xu, Junfa; Liu, Songhao

    2015-05-07

    This study aims to characterize and classify serum surface-enhanced Raman spectroscopy (SERS) spectra between bladder cancer patients and normal volunteers by genetic algorithms (GAs) combined with linear discriminate analysis (LDA). Two group serum SERS spectra excited with nanoparticles are collected from healthy volunteers (n = 36) and bladder cancer patients (n = 55). Six diagnostic Raman bands in the regions of 481-486, 682-687, 1018-1034, 1313-1323, 1450-1459 and 1582-1587 cm(-1) related to proteins, nucleic acids and lipids are picked out with the GAs and LDA. By the diagnostic models built with the identified six Raman bands, the improved diagnostic sensitivity of 90.9% and specificity of 100% were acquired for classifying bladder cancer patients from normal serum SERS spectra. The results are superior to the sensitivity of 74.6% and specificity of 97.2% obtained with principal component analysis by the same serum SERS spectra dataset. Receiver operating characteristic (ROC) curves further confirmed the efficiency of diagnostic algorithm based on GA-LDA technique. This exploratory work demonstrates that the serum SERS associated with GA-LDA technique has enormous potential to characterize and non-invasively detect bladder cancer through peripheral blood.

  18. Urinary pH, cigarette smoking and bladder cancer risk

    PubMed Central

    Alguacil, Juan; Kogevinas, Manolis; Silverman, Debra T.; Malats, Núria; Real, Francisco X.; García-Closas, Montserrat; Tardón, Adonina; Rivas, Manuel; Torà, Montserrat; García-Closas, Reina; Serra, Consol; Carrato, Alfredo; Pfeiffer, Ruth M.; Fortuny, Joan; Samanic, Claudine; Rothman, Nathaniel

    2011-01-01

    Glucuronide conjugates of 4-aminobiphenyl and its N-hydroxy metabolite can be rapidly hydrolyzed in acidic urine to undergo further metabolic activation and form DNA adducts in the urothelium. We conducted a large multicenter case–control study in Spain to explore the etiology of bladder cancer and evaluated the association between urine pH and bladder cancer risk, alone and in combination with cigarette smoking. In total, 712 incident urothelial cell carcinoma cases and 611 hospital controls directly measured their urine pH with dipsticks twice a day (first void in the morning and early in the evening) during four consecutive days 2 weeks after hospital discharge. We found that a consistently acidic urine pH ≤6.0 was associated with an increased risk of bladder cancer [odds ratio (OR) = 1.5, 95% confidence interval (CI): 1.2–1.9] compared with all other subjects. Furthermore, risk estimates for smoking intensity and risk of bladder cancer among current smokers tended to be higher for those with a consistently acidic urine (OR = 8.8, 11.5 and 23.8) compared with those without (OR = 4.3, 7.7 and 5.8, respectively, for 1–19, 20–29 and 30+ cigarettes per day; Pinteraction for 30+ cigarettes per day = 0.024). These results suggest that urine pH, which is determined primarily by diet and body surface area, may be an important modifier of smoking and risk of bladder cancer. PMID:21402590

  19. Bladder cancer among hairdressers: a meta-analysis.

    PubMed

    Harling, Melanie; Schablon, Anja; Schedlbauer, Grita; Dulon, Madeleine; Nienhaus, Albert

    2010-05-01

    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. 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. 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 > or = 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. In summary, our results showed an increased and statistically significant risk for bladder cancer among hairdressers, in particular for hairdressers in jobs held > or = 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.

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

    PubMed

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

    2016-02-01

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

  1. Kaempferol Modulates DNA Methylation and Downregulates DNMT3B in Bladder Cancer.

    PubMed

    Qiu, Wei; Lin, Jun; Zhu, Yichen; Zhang, Jian; Zeng, Liping; Su, Ming; Tian, Ye

    2017-01-01

    Genomic DNA methylation plays an important role in both the occurrence and development of bladder cancer. Kaempferol (Kae), a natural flavonoid that is present in many fruits and vegetables, exhibits potent anti-cancer effects in bladder cancer. Similar to other flavonoids, Kae possesses a flavan nucleus in its structure. This structure was reported to inhibit DNA methylation by suppressing DNA methyltransferases (DNMTs). However, whether Kae can inhibit DNA methylation remains unclear. Nude mice bearing bladder cancer were treated with Kae for 31 days. The genomic DNA was extracted from xenografts and the methylation changes was determined using an Illumina Infinium HumanMethylation 450 BeadChip Array. The ubiquitination was detected using immuno-precipitation assay. Our data indicated that Kae modulated DNA methylation in bladder cancer, inducing 103 differential DNA methylation positions (dDMPs) associated with genes (50 hyper-methylated and 53 hypo-methylated). DNA methylation is mostly relied on the levels of DNMTs. We observed that Kae specifically inhibited the protein levels of DNMT3B without altering the expression of DNMT1 or DNMT3A. However, Kae did not downregulate the transcription of DNMT3B. Interestingly, we observed that Kae induced a premature degradation of DNMT3B by inhibiting protein synthesis with cycloheximide (CHX). By blocking proteasome with MG132, we observed that Kae induced an increased ubiquitination of DNMT3B. These results suggested that Kae could induce the degradation of DNMT3B through ubiquitin-proteasome pathway. Our data indicated that Kae is a novel DNMT3B inhibitor, which may promote the degradation of DNMT3B in bladder cancer. © 2017 The Author(s)Published by S. Karger AG, Basel.

  2. Raman microscopy of bladder cancer cells expressing green fluorescent protein

    NASA Astrophysics Data System (ADS)

    Mandair, Gurjit S.; Han, Amy L.; Keller, Evan T.; Morris, Michael D.

    2016-11-01

    Gene engineering is a commonly used tool in cellular biology to determine changes in function or expression of downstream targets. However, the impact of genetic modulation on biochemical effects is less frequently evaluated. The aim of this study is to use Raman microscopy to assess the biochemical effects of gene silencing on T24 and UMUC-13 bladder cancer cell lines. Cellular biochemical information related to nucleic acid and lipogenic components was obtained from deconvolved Raman spectra. We show that the green fluorescence protein (GFP), the chromophore that served as a fluorescent reporter for gene silencing, could also be detected by Raman microscopy. Only the gene-silenced UMUC-13 cell lines exhibited low-to-moderate GFP fluorescence as determined by fluorescence imaging and Raman spectroscopic studies. Moreover, we show that gene silencing and cell phenotype had a greater effect on nucleic acid and lipogenic components with minimal interference from GFP expression. Gene silencing was also found to perturb cellular protein secondary structure in which the amount of disorderd protein increased at the expense of more ordered protein. Overall, our study identified the spectral signature for cellular GFP expression and elucidated the effects of gene silencing on cancer cell biochemistry and protein secondary structure.

  3. Micro-RNA profiling in kidney and bladder cancers.

    PubMed

    Gottardo, Fedra; Liu, Chang Gong; Ferracin, Manuela; Calin, George A; Fassan, Matteo; Bassi, Pierfrancesco; Sevignani, Cinzia; Byrne, Dolores; Negrini, Massimo; Pagano, Francesco; Gomella, Leonard G; Croce, Carlo M; Baffa, Raffaele

    2007-01-01

    Micro-RNAs are a group of small noncoding RNAs with modulator activity of gene expression. Recently, micro-RNA genes were found abnormally expressed in several types of cancers. To study the role of the micro-RNAs in human kidney and bladder cancer, we analyzed the expression profile of 245 micro-RNAs in kidney and bladder primary tumors. A total of 27 kidney specimens (20 carcinomas, 4 benign renal tumors, and 3 normal parenchyma) and 27 bladder specimens (25 urothelial carcinomas and 2 normal mucosa) were included in the study. Total RNA was used for hybridization on an oligonucleotide microchip for micro-RNA profiling developed in our laboratories. This microchip contains 368 probes in triplicate, corresponding to 245 human and mouse micro-RNA genes. A set of 4 human micro-RNAs (miR-28, miR-185, miR-27, and let-7f-2) were found significantly up-regulated in renal cell carcinoma (P < 0.05) compared to normal kidney. Human micro-RNAs miR-223, miR-26b, miR-221, miR-103-1, miR-185, miR-23b, miR-203, miR-17-5p, miR-23a, and miR-205 were significantly up-regulated in bladder cancers (P < 0.05) compared to normal bladder mucosa. Of the kidney cancers studied, there was no differential micro-RNA expression across various stages, whereas with increasing tumor-nodes-metastasis staging in bladder cancer, miR-26b showed a moderate decreasing trend (P = 0.082). Our results show that different micro-RNAs are deregulated in kidney and bladder cancer, suggesting the involvement of these genes in the development and progression of these malignancies. Further studies are needed to clarify the role of micro-RNAs in neoplastic transformation and to test the potential clinical usefulness of micro-RNAs microarrays as diagnostic and prognostic tool.

  4. How to optimally manage elderly bladder cancer patients?

    PubMed

    Soria, Francesco; Moschini, Marco; Korn, Stephan; Shariat, Shahrokh F

    2016-10-01

    Bladder cancer (BCa) is a disease of the elderly and as the population is aging, BCa will become an even bigger public health challenge in the future. Nowadays the correct management of BCa in the elderly remains controversial. The purpose of this article was to review the previous literature to summarize the current knowledge. Using Medline, a non-systematic review was performed including articles between January 2000 and February 2016 in order to describe the management of BCa in the elderly in all its aspects. English language original articles, reviews and editorials were selected based on their clinical relevance. In the literature, the definition of elderly is variable and based on chronological, not biological, age. BCa seems to be more aggressive in the elderly. The management of non-muscle invasive bladder cancer (NMIBC) does not strongly differ from younger patients, except for the role of adjuvant immunotherapy. In patients with muscle invasive bladder cancer (MIBC) the role of a multidisciplinary geriatric evaluation is potentially beneficial. The curative treatment in MIBC remains radical cystectomy (RC) and elderly patients should not be withheld a potentially life-saving intervention only based on chronological age. Patients unsuitable to a major surgical approach may be eligible for bladder-sparing techniques. Geriatric assessment could help identify the frail elderly and customize their perioperative care (i.e., pre and re habilitation). In conclusion the treatment of BCa in the elderly has to be patient-centered and focused on biological age and functional reserves.

  5. Imatinib radiosensitises bladder cancer by targeting homologous recombination

    PubMed Central

    Qiao, Boling; Kerr, Martin; Groselj, Blaz; Teo, Mark TW; Knowles, Margaret A; Bristow, Robert G; Phillips, Roger M; Kiltie, Anne E

    2013-01-01

    Radiotherapy is a major treatment modality used to treat muscle-invasive bladder cancer, with patient outcomes similar to surgery. However, radioresistance is a significant factor in treatment failure. Cell-free extracts of muscle-invasive bladder tumours are defective in non-homologous end-joining (NHEJ), and this phenotype might be exploited clinically by combining radiotherapy with a radiosensitising drug that targets homologous recombination (HR), thereby sparing normal tissues with intact NHEJ. The response of the HR protein RAD51 to radiation is inhibited by the small molecule tyrosine kinase inhibitor (TKI) imatinib. Stable RT112 bladder cancer Ku knockdown (Ku80KD) cells were generated using shRNA technology to mimic the invasive tumour phenotype, and also RAD51 knockdown (RAD51KD) cells to demonstrate imatinib’s pathway selectivity. Ku80KD, RAD51KD, non-silencing vector control and parental RT112 cells were treated with radiation in combination with either imatinib or lapatinib, which inhibits NHEJ, and cell survival assessed by clonogenic assay. Drug doses were chosen at approximately IC40 and IC10 (non-toxic) levels. Imatinib radiosensitised Ku80KD cells to a greater extent than RAD51KD or RT112 cells. In contrast, lapatinib radiosensitised RAD51KD and RT112 cells, but not Ku80KD cells. Taken together, our findings suggest a new application for imatinib in concurrent use with radiotherapy to treat muscle-invasive bladder cancer. PMID:23302228

  6. How to optimally manage elderly bladder cancer patients?

    PubMed Central

    Soria, Francesco; Moschini, Marco; Korn, Stephan

    2016-01-01

    Bladder cancer (BCa) is a disease of the elderly and as the population is aging, BCa will become an even bigger public health challenge in the future. Nowadays the correct management of BCa in the elderly remains controversial. The purpose of this article was to review the previous literature to summarize the current knowledge. Using Medline, a non-systematic review was performed including articles between January 2000 and February 2016 in order to describe the management of BCa in the elderly in all its aspects. English language original articles, reviews and editorials were selected based on their clinical relevance. In the literature, the definition of elderly is variable and based on chronological, not biological, age. BCa seems to be more aggressive in the elderly. The management of non-muscle invasive bladder cancer (NMIBC) does not strongly differ from younger patients, except for the role of adjuvant immunotherapy. In patients with muscle invasive bladder cancer (MIBC) the role of a multidisciplinary geriatric evaluation is potentially beneficial. The curative treatment in MIBC remains radical cystectomy (RC) and elderly patients should not be withheld a potentially life-saving intervention only based on chronological age. Patients unsuitable to a major surgical approach may be eligible for bladder-sparing techniques. Geriatric assessment could help identify the frail elderly and customize their perioperative care (i.e., pre and re habilitation). In conclusion the treatment of BCa in the elderly has to be patient-centered and focused on biological age and functional reserves. PMID:27785425

  7. Leak detection system and control using non-rigid bladder

    SciTech Connect

    Pillette, K.P.

    1980-11-11

    A portable system for early detection of leaks from suspect piping fittings, for example, as used on the ''christmas tree'' portion of a gas well provides an encapsulating bladder which sealably encapsulates the suspect fitting and collects leaks from the fitting. The apparatus provides, in the preferred embodiment, a bladder which can encase any suspect portion of the christmas tree (Or like piping system), such as for example, the choke jacket or other like fittings where maximum turbulence occurs as when gas or oil mixed with sand flows through the fitting. In the preferred embodiment, the collection of a leak within the bladder causes a regulator to operate a control valve and halt the flow of gas, oil, or like flowing material through the piping system of which the suspect fitting is a part. The system can be applied to any other similar existing and operating piping arrangement where the detection of leaks from suspect fittings is desirable. The portable bladder and shut off arrangement of the present invention has particular application in the offshore oil and gas industry, where it can perform a safety function on unmanned gas/oil well platforms.

  8. Controversies and challenges in research on urogenital schistosomiasis-associated bladder cancer

    PubMed Central

    Honeycutt, Jared; Hammam, Olfat; Fu, Chi-Ling; Hsieh, Michael H.

    2014-01-01

    Urogenital schistosomiasis, infection with Schistosoma haematobium, is linked to increased risk for the development of bladder cancer, but the importance of various mechanisms responsible for this association remains unclear, in part due to lack of sufficient and appropriate animal models. New advances in the study of this parasite, bladder regenerative processes, and human schistosomal bladder cancers may shed new light on the complex biological processes that connect S. haematobium infection to bladder carcinogenesis. PMID:24913983

  9. 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

  10. Partial allelotype of schistosomiasis-associated bladder cancer.

    PubMed

    Shaw, M E; Elder, P A; Abbas, A; Knowles, M A

    1999-03-01

    In Egypt and other regions of the Middle East where the trematode Schistosoma haematobium is endemic, bladder cancer is the most common adult cancer. Unlike bladder cancers in Western countries, which are predominantly transitional-cell carcinoma (TCC), these schistosomiasis-associated bladder cancers are predominantly squamous-cell carcinoma (SCC). Our aim was to assess a large series of schistosomiasis-associated bladder tumours for genetic alterations commonly found in TCC in the United Kingdom and the United States. We have carried out a partial allelotype of 70 tumours from patients with schistosomiasis. LOH was found on all chromosome arms studied (3p, 4p, 4q, 8p, 9p, 9q, 11p, 11q, 13q, 14q, 17p, 18q). The most frequent regions of LOH were 9p (65%), 17p (58%), 3p (40%), 9q (39%) and 8p (37%). LOH on 17p, where the TP53 gene is located, was more common in Egyptian TCC than in SCC. Similarly, 8p LOH was more common in TCC than SCC. The most striking difference between this group of tumours and TCCs from the United Kingdom and the United States was the high frequency of 9p LOH in the region of the CDKN2 gene (65%) and the relatively low frequency of 9q LOH (39%); 15 of 43 tumours with LOH of at least one marker on chromosome 9 showed LOH of 9p only. This suggests that a 9p gene, possibly CDKN2, may contribute to the development of the majority of schistosomiasis-associated bladder tumours but that genes on 9q play a much less important role.

  11. PSCA rs2294008 C > T polymorphism contributes to gastric and bladder cancer risk

    PubMed Central

    Wang, Meng; Wang, Xi-Jing; Ma, Yun-Feng; Ma, Xiao-Bin; Dai, Zhi-Ming; Lv, Ye; Lin, Shuai; Liu, Xing-Han; Yang, Peng-Tao; Dai, Zhi-Jun

    2015-01-01

    Background Previous studies suggested genetic variations in PSCA (prostate stem cell antigen) may confer the susceptibility of cancer. Many case–control studies have reported the relationship between PSCA rs2294008 C > T polymorphism and cancer, especially gastric cancer and bladder cancer. However, the results are inconsistent. This meta-analysis is aimed at evaluating the association of rs2294008 polymorphism with cancer risk. Methods The databases of PubMed, ISI Web of Knowledge, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) were searched for related publications. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of the associations. Fixed models were used when heterogeneity among studies was not detected, otherwise the random model was used. Results Twenty-six studies from 24 articles with 30,050 multiple cancer cases and 51,670 controls were pooled into this meta-analysis. The results showed that the rs2294008 polymorphism was associated with increased cancer risk in any genetic model (T vs C, OR: 1.18, 95% CI: 1.08–1.28; TT vs CC, OR: 1.36, 95% CI: 1.14–1.62; TC vs CC, OR: 1.29, 95% CI: 1.17–1.44; TT + TC vs CC, OR: 1.32, 95% CI: 1.18–1.49; TT vs TC + CC, OR: 1.15, 95% CI: 1.02–1.30). In stratified analysis by cancer type, we found that the T allele had a significant high risk of gastric and bladder cancer, but not in other cancers. In subgroup analysis by ethnicity, increased cancer risk was found in both Asians and Caucasians. Conclusion Our study suggested that the PSCA rs2294008 C > T polymorphism is a risk factor for cancer, especially in gastric and bladder cancer. PMID:25709466

  12. Antitumor effects of exogenous ganglioside GM3 on bladder cancer in an orthotopic cancer model.

    PubMed

    Wang, Hua; Isaji, Tomoya; Satoh, Makoto; Li, Dechuan; Arai, Yoichi; Gu, Jianguo

    2013-01-01

    To investigate the therapeutic effects of exogenous gangliosides GM3 on human bladder cancer cell lines and the severe combined immunodeficiency mouse model of orthotopic bladder cancer. Human bladder cancer cell lines YTS-1, T24, 5637, and KK47 were used in the study. In vitro cytotoxicity of GM3 was assessed using the cell counting kit-8. Cell adhesion was determined using a spreading assay. Phosphorylation of epidermal growth factor receptor was determined by Western blotting. In vivo, the orthotopic bladder cancer model was established using severe combined immunodeficiency mice and GM3 was administered intravesically by way of a transurethral catheter. GM3 inhibited the proliferation of all the bladder cancer cell lines tested. The addition of GM3 decreased cell adhesion and epidermal growth factor-dependent phosphorylation of epidermal growth factor receptor. Direct instillation of GM3 into the bladder of the orthotopic model significantly inhibited tumor growth. Our results suggest exogenous GM3 as a potential therapeutic agent for treating bladder cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. International pooled study on diet and bladder cancer: the bladder cancer, epidemiology and nutritional determinants (BLEND) study: design and baseline characteristics.

    PubMed

    Goossens, Maria E; Isa, Fatima; Brinkman, Maree; Mak, David; Reulen, Raoul; Wesselius, Anke; Benhamou, Simone; Bosetti, Cristina; Bueno-de-Mesquita, Bas; Carta, Angela; Allam, Md Farouk; Golka, Klaus; Grant, Eric J; Jiang, Xuejuan; Johnson, Kenneth C; Karagas, Margaret R; Kellen, Eliane; La Vecchia, Carlo; Lu, Chih-Ming; Marshall, James; Moysich, Kirsten; Pohlabeln, Hermann; Porru, Stefano; Steineck, Gunnar; Stern, Marianne C; Tang, Li; Taylor, Jack A; van den Brandt, Piet; Villeneuve, Paul J; Wakai, Kenji; Weiderpass, Elisabete; White, Emily; Wolk, Alicja; Zhang, Zuo-Feng; Buntinx, Frank; Zeegers, Maurice P

    2016-01-01

    In 2012, more than 400,000 urinary bladder cancer cases occurred worldwide, making it the 7(th) most common type of cancer. Although many previous studies focused on the relationship between diet and bladder cancer, the evidence related to specific food items or nutrients that could be involved in the development of bladder cancer remains inconclusive. Dietary components can either be, or be activated into, potential carcinogens through metabolism, or act to prevent carcinogen damage. The BLadder cancer, Epidemiology and Nutritional Determinants (BLEND) study was set up with the purpose of collecting individual patient data from observational studies on diet and bladder cancer. In total, data from 11,261 bladder cancer cases and 675,532 non-cases from 18 case-control and 6 cohort studies from all over the world were included with the aim to investigate the association between individual food items, nutrients and dietary patterns and risk of developing bladder cancer. The substantial number of cases included in this study will enable us to provide evidence with large statistical power, for dietary recommendations on the prevention of bladder cancer.

  14. Trends in the incidence of bladder cancer in Nova Scotia: a twenty-year perspective.

    PubMed

    McLellan, R A; French, C G; Bell, D G

    2003-06-01

    Bladder cancer is the most common malignant tumor of the urinary system. Tobacco smoking has been implicated as a major risk factor for the development of bladder cancer and Nova Scotia has some of the highest smoking rates in Canada. We examined trends in the incidence of bladder cancer in Nova Scotia between 1980 and 1999. Data on incident cases of bladder cancer diagnosed in Nova Scotia over a twenty-year period (1980 - 1999) were obtained from the Nova Scotia Cancer Registry. The age- standardized incidence and mortality due to bladder cancer was calculated for both genders. Trends in the incidence of bladder cancer during the study period were analyzed for three different age groups in each gender as an estimate of birth cohort. The average annual percent change (AAPC) in incidence of bladder cancer was calculated. Between 1980 and 1999, 3569 cases of bladder cancer were reported (male: female = 2.9:1). The overall incidence of bladder cancer increased in both males (27.5 to 39.5 cases per 100 000) and females (7.0 to 10.7 cases per 100 000). Mortality rates were stable. There was a trend towards an increase in bladder cancer rates for all age groups analyzed, with a substantial rise occurring in females less than 65 years of age. The AAPC in incidence of bladder cancer was +1.5 for males and +2.6 for females. We hypothesize that the rising incidence of bladder cancer in Nova Scotia, particularly in individuals less than 65 years of age, is related to changes in cigarette smoking practices during the past century. As the population ages, we are likely to see an increased incidence of bladder cancer in females.

  15. Evaluation of cell-free DNA in urine as a marker for bladder cancer diagnosis.

    PubMed

    Zancan, Matelda; Galdi, Francesca; Di Tonno, Fulvio; Mazzariol, Chiara; Orlando, Claudio; Malentacchi, Francesca; Agostini, Marco; Maran, Michela; Del Bianco, Paola; Fabricio, Aline S C; Murer, Bruno; Pianon, Carlo; Gion, Massimo

    2009-01-01

    The diagnosis and follow-up of bladder cancer are mainly based on cystoscopy, an invasive method which could be negative in case of flat malignancies such as carcinoma in situ. Other noninvasive diagnostic methods have not yet given satisfactory results. There is a need for a reliable yet noninvasive method for the detection of bladder cancer. Our aim was to investigate whether cell-free DNA quantified in urine (ucf-DNA) could be a useful marker for the diagnosis of bladder cancer. A standard urine test was performed in 150 naturally voided morning urine samples that were processed to obtain a quantitative evaluation of ucf-DNA. Leukocyturia and/or bacteriuria were found in 18 subjects, who were excluded from the study. Statistical analysis was performed on 45 bladder cancer patients and 87 healthy subjects. Ucf-DNA was extracted from urine samples by a spin column-based method and quantified using four different methods: GeneQuant Pro (Amersham Biosciences, Pittsburg, PA, USA), Quant-iT DNA high-sensitivity assay kit (Invitrogen, Carlsbad, CA, USA), Real-Time PCR (Applied Biosystems, Foster City, CA, USA), and NanoDrop 1000 (NanoDrop Technologies, Houston, TX, USA). Median free DNA quantification did not differ statistically between bladder cancer patients and healthy subjects. A receiver-operating characteristic (ROC) curve was developed to evaluate the diagnostic performance of ucf-DNA quantification for each method. The area under the ROC curve was 0.578 for GeneQuant Pro, 0.573 for the Quant-iT DNA high-sensitivity assay kit, 0.507 for Real-Time PCR, and 0.551 for NanoDrop 1000, which indicated that ucf-DNA quantification by these methods is not able to discriminate between the presence and absence of bladder cancer. No association was found between ucf-DNA quantification and tumor size or tumor focality. In conclusion, ucf-DNA isolated by a spin column-based method and quantified by GeneQuant Pro, Quant-iT DNA high-sensitivity assay kit, Real-Time PCR or Nano

  16. miR‑485‑5p inhibits bladder cancer metastasis by targeting HMGA2.

    PubMed

    Chen, Zhijun; Li, Qingwen; Wang, Sheng; Zhang, Jiajun

    2015-10-01

    MicroRNA (miRNA or miR)‑485 is a functional miRNA which has received much attention in recent years. However, little is known about the expression of miR‑485 or the role it plays in bladder cancer [namely in metastasis and epithelial‑mesenchymal transition (EMT)]. Thus, in the present study, we aimed to detect the expression of miR‑485 in human bladder cancer tissues and bladder cancer cell lines, and to examine the effects of miR‑485‑5p on bladder cancer cell metastasis and EMT. We found that the expression of miR‑485‑5p was downregulated in the human bladder cancer tissues and different bladder cancer cell lines compared with the normal tissues and cell lines, as demonstrated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). We enforced the expression of miR‑485‑5p in T24 cells and inhibited the expression of miR‑485‑5p in SW780 cells by transfection with miR‑485‑5p mimic or miR‑485‑5p inhibitor, respectively. The ectopic expression of miR‑485‑5p was shown to inhibit cell metastasis and EMT, whereas the inhibition of miR‑485‑5p expression promoted cell metastasis and EMT, as shown by transwell‑matrigel assay, cell adhesion assay and western blot analysis. Furthermore, a luciferase reporter assay revealed that high mobility group AT‑hook 2 (HMGA2) was a direct target of miR‑485‑5p and that the overexpression of HMGA2 reversed the effects of miR‑485‑5p on cell metastasis and EMT. In conclusion and to the very best of our knowledge, the present study, for the first time, identified miR‑485‑5p as a suppressive miRNA in human bladder cancer, and demonstrated that miR‑485‑5p inhibits cell metastasis and EMT at least partly through the suppression of HMGA2 expression.

  17. Long Noncoding RNA Cancer Susceptibility Candidate 8 Suppresses the Proliferation of Bladder Cancer Cells via Regulating Glycolysis.

    PubMed

    Hu, Renguang; Zhong, Peng; Xiong, Lu; Duan, Liangbin

    2017-09-01

    Increasing evidence highlights the critical regulatory role of long noncoding RNAs (lncRNAs) in carcinogenesis. Bladder cancer has become the most prevalent urologic malignancy, which is commonly diagnosed among adults. In this study, we showed that the lncRNA cancer susceptibility candidate 8 (CASC8) is significantly downregulated in bladder cancers and associated with the advanced stage of bladder cancer patients. Overexpression of CASC8 remarkably suppressed the bladder cancer cell proliferation. Mechanistically, we illustrated that CASC8 reduced the glycolysis of bladder cancer cells via interacting with the fibroblast growth factor receptor 1 (FGFR1). The binding of CASC8 with FGFR1 inhibits FGFR1-mediated lactate dehydrogenase A phosphorylation, which attenuates the conversion of pyruvate into lactate. Collectively, our findings uncovered the pivotal role of CASC8 in bladder tumorigenesis and suggested that CASC8 may function as a candidate biomarker for the diagnosis of bladder cancer.

  18. DAPK Promoter Methylation and Bladder Cancer Risk: A Systematic Review and Meta-Analysis

    PubMed Central

    Zhang, Zhensheng; Zeng, Shuxiong; Liu, Anwei; Tang, Shijie; Ren, Qian; Sun, Yinghao; Xu, Chuanliang

    2016-01-01

    Background Methylation of tumor suppressor gene promoter leads to transcription inactivation and is involved in tumorigenesis. Several studies demonstrate a potential association between the Death-Associated Protein Kinase (DAPK) gene promoter methylation and bladder cancer risk, tumor stage and histological grade. Due to inconsistent results of these studies, we performed this meta-analysis to ascertain the association. Methods Studies were retrieved from the PubMed, Embase, Web of Science and the Cochrane Library databases. Study selection and data extraction were executed by two reviewers independently. Meta-analysis was performed using Stata 13.0 and Review Manager 5.3 software. Results A total of 21 articles involving 15 case control and 8 case series studies were included in this meta-analysis. DAPK promoter methylation was associated with bladder cancer risk (OR: 5.81; 95%CI = 3.83–8.82, P<0.00001). The frequency of DAPK promoter methylation was equal in bladder cancer tissue and paired adjacent normal tissue (OR: 0.87; 95%CI = 0.31–2.48, P = 0.794). Furthermore, DAPK promoter methylation was associated with higher histological grade (OR: 1.52; 95%CI = 1.10–2.09, P = 0.011) but not associated with tumor stage (OR: 1.12; 95%CI = 0.67–1.87, P = 0.668). Conclusions The result suggests that DAPK promoter methylation is significantly increased in bladder cancer patients compared to normal controls. DAPK promoter methylation could serve as a biomarker for bladder cancer detection and management. PMID:27907054

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

    PubMed Central

    Ohishi, Tomokazu; Koga, Fumitaka; Migita, Toshiro

    2015-01-01

    Bladder cancer (BC), the most common cancer arising from the human urinary tract, consists of two major clinicopathological phenotypes: muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). MIBC frequently metastasizes and is associated with an unfavorable prognosis. A certain proportion of patients with metastatic BC can achieve a remission with systemic chemotherapy; however, the disease relapses in most cases. Evidence suggests that MIBC comprises a small population of cancer stem cells (CSCs), which may be resistant to these treatments and may be able to form new tumors in the bladder or other organs. Therefore, the unambiguous identification of bladder CSCs and the development of targeted therapies are urgently needed. Nevertheless, it remains unclear where bladder CSCs originate and how they are generated. We review recent studies on bladder CSCs, specifically focusing on their proposed origin and the possible therapeutic options based on the CSC theory. PMID:26729098

  20. Personalized medicine for targeted and platinum-based chemotherapy of lung and bladder cancer

    PubMed Central

    Cimino, George D; Pan, Chong-xian; Henderson, Paul T

    2013-01-01

    The personalized medicine revolution is occurring for cancer chemotherapy. Biomarkers are increasingly capable of distinguishing genotypic or phenotypic traits of individual tumors, and are being linked to the selection of treatment protocols. This review covers the molecular basis for biomarkers of response to targeted and cytotoxic lung and bladder cancer treatment with an emphasis on platinum-based chemotherapy. Platinum derivatives are a class of drugs commonly employed against solid tumors that kill cells by covalent attachment to DNA. Platinum–DNA adduct levels in patient tissues have been correlated to response and survival. The sensitivity and precision of adduct detection has increased to the point of enabling subtherapeutic dosing for diagnostics applications, termed diagnostic microdosing, prior to the initiation of full-dose therapy. The clinical status of this unique phenotypic marker for lung and bladder cancer applications is detailed along with discussion of future applications. PMID:23394702

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

    PubMed Central

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

    2009-01-01

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

  2. Urinary bladder preservation for muscle-invasive bladder cancer: a survey among radiation oncologists of Lombardy, Italy.

    PubMed

    Jereczek-Fossa, Barbara Alicja; Colombo, Renzo; Magnani, Tiziana; Fodor, Cristiana; Gerardi, Marianna Alessandra; Antognoni, Paolo; Barsacchi, Lucia; Bedini, Nice; Bracelli, Stefano; Buffoli, Alberto; Cagna, Emanuela; Catalano, Gianpiero; Gottardo, Stefania; Italia, Corrado; Ivaldi, Giovanni Battista; Masciullo, Stefano; Merlotti, Anna; Sarti, Enrico; Scorsetti, Marta; Serafini, Flavia; Toninelli, Mariasole; Vitali, Elisabetta; Valdagni, Riccardo; Villa, Elisa; Zerini, Dario; De Cobelli, Ottavio; Orecchia, Roberto

    2015-01-01

    Bladder preservation is a treatment option in muscle-invasive bladder carcinoma. The most investigated approach is a trimodality schedule including maximum transurethral resection of bladder tumor (TURBT) followed by chemoradiotherapy. Our aim was to evaluate the use of bladder preservation by radiation oncologists of the Lombardy region in Italy. A survey with 13 items regarding data of 2012 was sent to all 32 radiotherapy centers within the collaboration between the Lombardy Oncological Network and the Lombardy Section of the Italian Society of Oncological Radiotherapy. Thirteen centers (41%) answered the survey; the presented data come from 11 active centers. In these centers, 11,748 patients were treated with external-beam radiotherapy in 2012, 100 of whom having bladder cancer (0.9%). 74/100 patients received radiotherapy as palliative treatment for T, N or M lesions. A further 9 and 5 patients received radiotherapy for oligometastatic disease (ablative doses to small volumes) and postoperatively, respectively. Bladder preservation was performed in 12 cases and included trimodality and other strategies (mainly TURBT followed by radiotherapy). A multidisciplinary urology tumor board met regularly in 5 of 11 centers. All responders declared their interest in the Lombardy multicenter collaboration on bladder preservation. Our survey showed that bladder preservation is rarely used in Lombardy despite the availability of the latest radiotherapy technologies and the presence of an urology tumor board in half of the centers. The initiative of multicenter and multidisciplinary collaboration was undertaken to prepare the platform for bladder preservation as a treatment option in selected patients.

  3. Effect of cranberry juice concentrate on chemically-induced urinary bladder cancers

    PubMed Central

    Prasain, Jeevan K.; Jones, Kenneth; Moore, Ray; Barnes, Stephen; Leahy, Marge; Roderick, Robin; Juliana, M. Margaret; Grubbs, Clinton J.

    2009-01-01

    The chemopreventive efficacy of cranberry juice concentrate in an experimental model of urinary bladder cancer was evaluated using female Fischer-344 rats. The animals received N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) for a period of eight weeks. Cranberry juice concentrate was administered at doses of 1.0 or 0.5 ml/rat/ day beginning one week after the final OH-BBN treatment and continuing until the end of the study. The urinary bladders of all the rats were weighed and examined grossly for lesions, and all masses were submitted for pathological evaluation. A dose-dependent preventive effect of cranberry treatment was observed, with a reduced number of urinary bladder cancers (38%) in the 1.0 ml/rat/day group versus the control group. The cranberry extract neither affected body weight gain nor caused other signs of toxicity. For the metabolic studies, serum and urine were collected at 4 and 12 h after the administration of the cranberry juice concentrate and were analyzed by LC-MS/MS. Quercetin and its methylated derivative were detected in the urine samples. However, no quercetin was detected in the serum samples, indicating its poor bioavailability. These data suggest that components of cranberries may be effective in preventing urinary bladder carcinogenesis. PMID:18497966

  4. Ten genetic polymorphisms in bladder cancer.

    PubMed Central

    Cartwright, R A; Adib, R; Appleyard, I; Coxon, J G; Glashan, R W; Richards, B; Robinson, M R; Sunderland, E; Barham-Hall, D

    1983-01-01

    Data are presented on a group of cases of primary carcinoma of the bladder, detailing red cell surface blood group antigenic phenotypes, serum haptoglobin phenotypes, and some red cell isoenzyme phenotypes. Account is taken of the stage of the disease at presentation. The results are compared with corresponding phenotype frequencies in groups of presumed healthy persons originating either in Yorkshire or County Durham. Differences in relative incidences were found in the haptoglobin, phosphoglucomutase (PGM), and some other systems. These are both differences between all cases and controls and between particular stages at presentation and controls. PMID:6221102

  5. Organic cation secretion by Cancer borealis urinary bladder

    SciTech Connect

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

    1987-01-01

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

  6. Alternating chemo-radiotherapy in bladder cancer: A conservative approach

    SciTech Connect

    Orsatti, M.; Franzone, P.; Giudici, S.

    1995-08-30

    The aim of this Phase II study was to determine a bladder-sparing treatment in patients with invasive bladder cancer, allowing a better quality of life. Objectives were to test toxicity and disease-free and overall survival of patients given an alternated chemo-radiotherapy definitive treatment. Seventy-six patients with bladder cancer Stage T1G3 through T4 N0 M0 were entered in the same chemotherapy regimen (Cisplatin 20 mg/mq and 5-Fluorouracil 200 mg/mq daily for 5 days) alternated with different radiotherapy scheduling, the first 18 patients received two cycles of 20 Gy/10 fractions/12 days each; the second group of 58 patients received two cycles of 25 Gy/10 fractions/12 days each (the last 21 patients received Methotrexate 40 mg/mq instead of 5-Fluorouracil). A clinical complete response was observed in 57 patients (81%), partial response in 7 patients (10%), and a nonresponse in 6 patients (9%). At a median follow-up of 45 months, 33 patients (47%) were alive and free of tumor. The 6-year overall survival and progression-free survival was 42% and 40%, respectively. Systemic side effects were mild, while a moderate or severe local toxicity was observed in 14 patients and 13 patients (about 20%), respectively. Our conservative combination treatment allowed bladder-sparing in a high rate of patients and resulted in a survival comparable to that reported after radical cystectomy. 34 refs., 4 figs., 5 tabs.

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

    SciTech Connect

    Tunio, Mutahir A.; Hashmi, Altaf; Qayyum, Abdul; Mohsin, Rehan; Zaeem, Ahmed

    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-CCRT (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.

  8. Quercetin induces bladder cancer cells apoptosis by activation of AMPK signaling pathway.

    PubMed

    Su, Qiongli; Peng, Mei; Zhang, Yuqing; Xu, Wanjun; Darko, Kwame Oteng; Tao, Ting; Huang, Yanjun; Tao, Xiaojun; Yang, Xiaoping

    2016-01-01

    Quercetin, a natural existing polyphenol compound, has shown anticancer capacity for liver, breast, nasopharyngeal and prostate carcinoma but has not been clinically approved yet. This might be due to lack of clear mechanistic picture. Bladder cancer is one of the most common cancers of the urinary tract in the world. In China, bladder cancer has the highest rate of incidence out of all malignancies of the urinary system. The anticancer application of quercetin on bladder cancer has not been investigated either. This study was aimed to examine the mechanisms of quercetin on inhibition of bladder cancer. First, two human and one murine bladder cancer cell lines were tested in vitro for inhibitory sensitivity by MTT and cologenic assays. Second, AMPK pathway including 4E-BP1 and S6K were examined by western blot. Quercetin induces apoptosis and inhibits migration. We are the first to show that quercetin displays potent inhibition on bladder cancer cells via activation of AMPK pathway.

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

    PubMed Central

    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

    2017-01-01

    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. PMID:28445934

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

    PubMed Central

    Franzen, Carrie A.; Simms, Patricia E.; Van Huis, Adam F.; Foreman, Kimberly E.; Kuo, Paul C.; Gupta, Gopal N.

    2014-01-01

    Bladder tumors represent a special therapeutic challenge as they have a high recurrence rate requiring repeated interventions and may progress to invasive or metastatic disease. Exosomes carry proteins implicated in bladder cancer progression and have been implicated in bladder cancer cell survival. Here, we characterized exosome uptake and internalization by human bladder cancer cells using Amnis ImageStreamX, an image cytometer. Exosomes were isolated by ultracentrifugation from bladder cancer culture conditioned supernatant, labeled with PKH-26, and analyzed on the ImageStreamX with an internal standard added to determine concentration. Exosomes were cocultured with bladder cancer cells and analyzed for internalization. Using the IDEAS software, we determined exosome uptake based on the number of PKH-26+ spots and overall PKH-26 fluorescence intensity. Using unlabeled beads of a known concentration and size, we were able to determine concentrations of exosomes isolated from bladder cancer cells. We measured exosome uptake by recipient bladder cancer cells, and we demonstrated that uptake is dose and time dependent. Finally, we found that uptake is active and specific, which can be partially blocked by heparin treatment. The characterization of cellular uptake and internalization by bladder cancer cells may shed light on the role of exosomes on bladder cancer recurrence and progression. PMID:24575409

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

    PubMed Central

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

    2016-01-01

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

  12. Occupation and cancer in London: an investigation into nasal and bladder cancer using the Cancer Atlas.

    PubMed Central

    Baxter, P J; McDowall, M E

    1986-01-01

    The Atlas of Cancer Mortality for England and Wales showed pronounced excesses of male mortality from nasal and bladder cancer in certain London boroughs. These excesses were investigated by case-referent studies using death certificate data for male deaths, 1968-78. Nasal cancer was found to be significantly associated with occupations involving heavy exposure to wood dust. Bladder cancer was significantly associated with occupations in road transport driving and in the handling of leather, whereas consistently raised relative risk ratios were also found for wood-workers, engineering fitters, printers, machinists, plumbers, and motor mechanics. These findings highlight the potential role of occupational factors in cancer causation in London. Images PMID:3947560

  13. Point-of-care clinical documentation: assessment of a bladder cancer informatics tool (eCancerCareBladder): a randomized controlled study of efficacy, efficiency and user friendliness compared with standard electronic medical records.

    PubMed

    Bostrom, Peter J; Toren, Paul J; Xi, Hao; Chow, Raymond; Truong, Tran; Liu, Justin; Lane, Kelly; Legere, Laura; Chagpar, Anjum; Zlotta, Alexandre R; Finelli, Antonio; Fleshner, Neil E; Grober, Ethan D; Jewett, Michael A S

    2011-01-01

    To compare the use of structured reporting software and the standard electronic medical records (EMR) in the management of patients with bladder cancer. The use of a human factors laboratory to study management of disease using simulated clinical scenarios was also assessed. eCancerCare(Bladder) and the EMR were used to retrieve data and produce clinical reports. Twelve participants (four attending staff, four fellows, and four residents) used either eCancerCare(Bladder) or the EMR in two clinical scenarios simulating cystoscopy surveillance visits for bladder cancer follow-up. Time to retrieve and quality of review of the patient history; time to produce and completeness of a cystoscopy report. Finally, participants provided a global assessment of their computer literacy, familiarity with the two systems, and system preference. eCancerCare(Bladder) was faster for data retrieval (scenario 1: 146 s vs 245 s, p=0.019; scenario 2: 306 vs 415 s, NS), but non-significantly slower to generate a clinical report. The quality of the report was better in the eCancerCare(Bladder) system (scenario 1: p<0.001; scenario 2: p=0.11). User satisfaction was higher with the eCancerCare(Bladder) system, and 11/12 participants preferred to use this system. The small sample size affected the power of our study to detect differences. Use of a specific data management tool does not appear to significantly reduce user time, but the results suggest improvement in the level of care and documentation and preference by users. Also, the use of simulated scenarios in a laboratory setting appears to be a valid method for comparing the usability of clinical software.

  14. mTOR inhibitors in urinary bladder cancer.

    PubMed

    Pinto-Leite, R; Arantes-Rodrigues, R; Sousa, Nuno; Oliveira, P A; Santos, L

    2016-09-01

    Despite the great scientific advances that have been made in cancer treatment, there is still much to do, particularly with regard to urinary bladder cancer. Some of the drugs used in urinary bladder cancer treatment have been in use for more than 30 years and show reduced effectiveness and high recurrence rates. There have been several attempts to find new and more effective drugs, to be used alone or in combination with the drugs already in use, in order to overcome this situation.The biologically important mammalian target of rapamycin (mTOR) pathway is altered in cancer and mTOR inhibitors have raised many expectations as potentially important anticancer drugs. In this article, the authors will review the mTOR pathway and present their experiences of the use of some mTOR inhibitors, sirolimus, everolimus and temsirolimus, in isolation and in conjunction with non-mTOR inhibitors cisplatin and gemcitabine, on urinary bladder tumour cell lines. The non-muscle-invasive cell line, 5637, is the only one that exhibits a small alteration in the mTOR and AKT phosphorylation after rapalogs exposure. Also, there was a small inhibition of cell proliferation. With gemcitabine plus everolimus or temsirolimus, the results were encouraging as a more effective response was noticed with both combinations, especially in the 5637 and T24 cell lines. Cisplatin associated with everolimus or temsirolimus also gave promising results, as an antiproliferative effect was observed when the drugs were associated, in particular on the 5637 and HT1376 cell lines. Everolimus or temsirolimus in conjunction with gemcitabine or cisplatin could have an important role to play in urinary bladder cancer treatment, depending on the tumour grading.

  15. Chemotherapy in advanced bladder cancer: current status and future

    PubMed Central

    2011-01-01

    Bladder cancer occurs in the majority of cases in males. It represents the seventh most common cancer and the ninth most common cause of cancer deaths for men. Transitional cell carcinoma is the most predominant histological type. Bladder cancer is highly chemosensitive. In metastatic setting, chemotherapy based on cisplatin should be considered as standard treatment of choice for patients with good performance status (0-1) and good renal function-glomerular filtration rate (GFR) > 60 mL/min. The standard treatment is based on cisplatin chemotherapy regimens type MVAC, HD-MVAC, gemcitabine plus cisplatin (GC) or dose dense GC. In unfit patients, carboplatin based regimes; gemcitabine plus carboplatin or methotrexate plus carboplatin plus vinblastine (MCAVI) are reasonable options. The role of targeted therapies when used alone, or in combination with chemotherapy, or in maintenance, was evaluated; targeting angiogenesis seem to be very promising. The purpose of this literature review is to highlight the role of chemotherapy in the management of advanced transitional cell carcinoma of the bladder. PMID:21906310

  16. In vivo testing of a prototype system providing simultaneous white light and near infrared autofluorescence image acquisition for detection of bladder cancer.

    PubMed

    Jacobson, Michael C; deVere White, Ralph; Demos, Stavros G

    2012-03-01

    A prototype instrument developed to provide simultaneously ordinary visual endoscopy together with near infrared (NIR) autofluorescence imaging via parallel image acquisition is demonstrated. The two images are recorded concurrently and the instrument interfaces with any ordinary endoscope. Preliminary results of a pilot study focused on imaging of bladder tumors in vivo using this instrumentation are presented. The experimental results demonstrate the capabilities of this instrumentation design, imaging methodology, and define the current limitation for further development of the system.

  17. Micropapillary Bladder Cancer: Insights from the National Cancer Database

    PubMed Central

    Sui, Wilson; Matulay, Justin T.; James, Maxwell B.; Onyeji, Ifeanyi C.; Theofanides, Marissa C.; RoyChoudhury, Arindam; DeCastro, G. Joel; Wenske, Sven

    2016-01-01

    Introduction: Micropapillary bladder cancer (MPBC) is a variant histology of urothelial carcinoma (UC) that is associated with poor outcomes however given its rarity, little is known outside of institutional reports. We sought to use a population-level cancer database to assess survival outcomes in patients treated with surgery, radiation therapy and/or chemotherapy. Materials and Methods: The National Cancer Database (NCDB) was queried for all cases of MPBC and UC using International Classification of Disease-O-3 morphologic codes between 2004–2014. Primary outcome was survival outcomes stratified by treatment modality. Treatments included radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC). Results: Overall 869 patients with MPBC and 389,603 patients with UC met the inclusion criteria. Median age of the MPBC cohort was 69.9 years (58.9–80.9) with the majority of the cohort presenting with high-grade (89.3%) and muscle invasive or locally advanced disease (47.6%). For cT1 MPBC, outcomes of RC and BPS were not statistically different. For≥cT2 disease, NAC showed a survival benefit compared with RC alone for UC but not for MPBC. On multivariable analysis, MPBC histology independently predicted worse increased risk of death. On subanalysis of the MPBC RC patients, NAC did not improve survival outcomes compared with RC alone. Conclusions: Neoadjuvant chemotherapy utilization and early cystectomy did not show a survival benefit in patients with MPBC. This histology independently predicts decreased survival and prognosis is poor regardless of treatment modality. Further research should focus on developing better treatment options for this rare disease. PMID:28035322

  18. [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.

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

    SciTech Connect

    Conde, Vanessa R.; Oliveira, Pedro F.; Ramalhosa, Elsa; Pereira, José A.; Alves, Marco G.; Silva, Branca M.

    2015-07-01

    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 similar 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.

  20. Cross-species comparison of orthologous gene expression in human bladder cancer and carcinogen-induced rodent models

    PubMed Central

    Lu, Yan; Liu, Pengyuan; Wen, Weidong; Grubbs, Clinton J; Townsend, Reid R; Malone, James P; Lubet, Ronald A; You, Ming

    2011-01-01

    Genes differentially expressed by tumor cells represent promising drug targets for anti-cancer therapy. Such candidate genes need to be validated in appropriate animal models. This study examined the suitability of rodent models of bladder cancer in B6D2F1 mice and Fischer-344 rats to model clinical bladder cancer specimens in humans. Using a global gene expression approach cross-species analysis showed that 13-34% of total genes in the genome were differentially expressed between tumor and normal tissues in each of five datasets from humans, rats, and mice. About 20% of these differentially expressed genes overlapped among species, corresponding to 2.6 to 4.8% of total genes in the genome. Several genes were consistently dysregulated in bladder tumors in both humans and rodents. Notably, CNN1, MYL9, PDLIM3, ITIH5, MYH11, PCP4 and FM05 were found to commonly down-regulated; while T0P2A, CCNB2, KIF20A and RRM2 were up-regulated. These genes are likely to have conserved functions contributing to bladder carcinogenesis. Gene set enrichment analysis detected a number of molecular pathways commonly activated in both humans and rodent bladder cancer. These pathways affect the cell cycle, HIF-1 and MYC expression, and regulation of apoptosis. We also compared expression changes at mRNA and protein levels in the rat model and identified several genes/proteins exhibiting concordant changes in bladder tumors, including ANXA1, ANXA2, CA2, KRT14, LDHA, LGALS4, SERPINA1, KRT18 and LDHB. In general, rodent models of bladder cancer represent the clinical disease to an extent that will allow successful mining of target genes and permit studies on the molecular mechanisms of bladder carcinogenesis. PMID:21139803

  1. Screening for Bladder and Other Urothelial Cancers

    MedlinePlus

    ... Events Scientific Meetings & Lectures Conferences Advisory Board Meetings Social Media Events Cancer Currents Blog All Press Releases 2017 ... Events Scientific Meetings & Lectures Conferences Advisory Board Meetings Social Media Cancer Currents Blog About NCI NCI Overview History ...

  2. Radiochemotherapy With Cisplatin and 5-Fluorouracil After Transurethral Surgery in Patients With Bladder Cancer

    SciTech Connect

    Weiss, Christian . E-mail: Christian.Weiss@strahlen.med.uni-erlangen.de; Engehausen, Dirk G.; Krause, Frens S.; Papadopoulos, Thomas; Dunst, Juergen; Sauer, Rolf; Roedel, Claus

    2007-07-15

    Purpose: To give an update on the long-term outcome of an intensified protocol of combined radiochemotherapy (RCT) with 5-fluorouracil (5-FU) and cisplatin after initial transurethral resection of bladder tumor (TURBT) with selective organ preservation in bladder cancer. Methods and Materials: One hundred twelve patients with muscle-invading or high-risk T1 (G3, associated Tis, multifocality, diameter >5 cm) bladder cancer were enrolled in a protocol of TURBT followed by concurrent cisplatin (20 mg/m{sup 2}/day as 30-min infusion) and 5-FU (600 mg/m{sup 2}/day as 120-h continuous infusion), administered on Days 1-5 and 29-33 of radiotherapy. Response to treatment was evaluated by restaging TURBT 4-6 weeks after RCT. In case of invasive residual tumor or recurrence, salvage cystectomy was recommended. Results: Ninety-nine patients (88.4%) had no detectable tumor at restaging TURBT; 71 patients (72%) have been continuously free from local recurrence or distant metastasis. Superficial relapse occurred in 13 patients and muscle-invasive recurrence in 11 patients. Overall and cause-specific survival rates for all patients were 74% and 82% at 5 years, respectively. Of all surviving patients, 82% maintained their own bladder, 79% of whom were delighted or pleased with their urinary condition. Hematologic Grade 3/4 toxicity occurred in 23%/6% and Grade 3 diarrhea in 21% of patients. One patient required salvage cystectomy due to a shrinking bladder. Conclusion: Concurrent RCT with 5-FU/cisplatin has been associated with acceptable acute and long-term toxicity. Overall and cause-specific survival rates are encouraging. More than 80% of patients preserved their well-functioning bladder.

  3. Patterns of Bladder Preservation Therapy Utilization for Muscle-Invasive Bladder Cancer.

    PubMed

    Rose, Tracy L; Deal, Allison M; Ladoire, Sylvain; Créhange, Gilles; Galsky, Matthew D; Rosenberg, Jonathan E; Bellmunt, Joaquim; Wimalasingham, Akhila; Wong, Yu-Ning; Harshman, Lauren C; Chowdhury, Simon; Niegisch, Guenter; Liontos, Michalis; Yu, Evan Y; Pal, Sumanta K; Chen, Ronald C; Wang, Andrew Z; Nielsen, Matthew E; Smith, Angela B; Milowsky, Matthew I

    2016-10-27

    Background: Trimodality bladder preservation therapy (BPT) in muscle invasive bladder cancer (MIBC) includes a maximal transurethral resection followed by concurrent chemoradiotherapy as an alternative to radical cystectomy (RC) in appropriately selected patients, or as a treatment option in non-cystectomy candidates. Several chemotherapy regimens can be used in BPT, but little is known about current practice patterns. Objective: To describe utilization patterns of BPT and associated survival outcomes in MIBC. Methods: Data were collected from the Retrospective International Study of Cancers of the Urothelial Tract (RISC), a database of 3,024 consecutive patients from 29 international academic centers from 2005 to 2013. Patients with clinical T2-T4aN0M0 urothelial cancer of the bladder were included. Results: 265 patients received BPT. Compared with the 1,447 patients who received RC, BPT patients were older, had poorer performance status, and had more comorbidities (p < 0.01 for all). Median overall survival (OS) was similar for patients treated with curative radiation doses in BPT and patients treated with RC (41 vs 46 months, p = 0.33, respectively). 45% of BPT patients received concurrent chemotherapy with radiation. The most common regimens included cisplatin alone (23%), carboplatin alone (22%), gemcitabine alone (10%), paclitaxel alone (9%), and 5-FU+mitomycin (5%). There were no significant differences in survival among chemotherapy regimens. Only 10 patients (4% of BPT patients) underwent salvage cystectomy. Conclusions: In clinical practice, BPT patients have similar survival to RC patients when treated with curative radiotherapy doses. Choice of concurrent chemotherapy regimen varied widely with no clear standard. Salvage cystectomy is rarely performed. Continued research is needed on the comparative effectiveness among BPT and RC, and among chemotherapy regimens in BPT.

  4. Patterns of Bladder Preservation Therapy Utilization for Muscle-Invasive Bladder Cancer

    PubMed Central

    Rose, Tracy L.; Deal, Allison M.; Ladoire, Sylvain; Créhange, Gilles; Galsky, Matthew D.; Rosenberg, Jonathan E.; Bellmunt, Joaquim; Wimalasingham, Akhila; Wong, Yu-Ning; Harshman, Lauren C.; Chowdhury, Simon; Niegisch, Guenter; Liontos, Michalis; Yu, Evan Y.; Pal, Sumanta K.; Chen, Ronald C.; Wang, Andrew Z.; Nielsen, Matthew E.; Smith, Angela B.; Milowsky, Matthew I.

    2016-01-01

    Background: Trimodality bladder preservation therapy (BPT) in muscle invasive bladder cancer (MIBC) includes a maximal transurethral resection followed by concurrent chemoradiotherapy as an alternative to radical cystectomy (RC) in appropriately selected patients, or as a treatment option in non-cystectomy candidates. Several chemotherapy regimens can be used in BPT, but little is known about current practice patterns. Objective: To describe utilization patterns of BPT and associated survival outcomes in MIBC. Methods: Data were collected from the Retrospective International Study of Cancers of the Urothelial Tract (RISC), a database of 3,024 consecutive patients from 29 international academic centers from 2005 to 2013. Patients with clinical T2-T4aN0M0 urothelial cancer of the bladder were included. Results: 265 patients received BPT. Compared with the 1,447 patients who received RC, BPT patients were older, had poorer performance status, and had more comorbidities (p < 0.01 for all). Median overall survival (OS) was similar for patients treated with curative radiation doses in BPT and patients treated with RC (41 vs 46 months, p = 0.33, respectively). 45% of BPT patients received concurrent chemotherapy with radiation. The most common regimens included cisplatin alone (23%), carboplatin alone (22%), gemcitabine alone (10%), paclitaxel alone (9%), and 5-FU+mitomycin (5%). There were no significant differences in survival among chemotherapy regimens. Only 10 patients (4% of BPT patients) underwent salvage cystectomy. Conclusions: In clinical practice, BPT patients have similar survival to RC patients when treated with curative radiotherapy doses. Choice of concurrent chemotherapy regimen varied widely with no clear standard. Salvage cystectomy is rarely performed. Continued research is needed on the comparative effectiveness among BPT and RC, and among chemotherapy regimens in BPT. PMID:28035321

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

    PubMed Central

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

    1981-01-01

    A case-control study, undertaken to identify reasons for the exceptionally high incidence of bladder cancer among men in the Chicoutimi census division of the province of Quebec, revealed an increased risk associated with employment in the electrolysis department of an aluminum reduction plant. The estimated relative risk was 2.83 (95% confidence interval; 1.06 to 7.54). An interaction was found between such employment and cigarette smoking, resulting in a combined relative risk of 5.70 (95% confidence interval: 2.00 to 12.30). These findings suggest that employment in an aluminum reduction plant accounts for part of the excess of bladder cancer in the region studied. PMID:7214271

  6. Bladder cancer: a review of diagnosis and management.

    PubMed Central

    Metts, M. C.; Metts, J. C.; Milito, S. J.; Thomas, C. R.

    2000-01-01

    Bladder cancer is the fourth most commonly diagnosed malignancy in men and the eighth most common in women. It represents a spectrum of disease, ranging from superficial, well-differentiated disease, which does not significantly impact survival, to highly malignant tumors for which long term survival may be dismal. Transitional-cell carcinoma, which constitutes the vast majority of bladder cancers in the United States, may develop as carcinoma in situ or as invasive carcinoma. This article focuses on transitional-cell carcinoma with a review of the major aspects of the disease, including the epidemiology, diagnosis and staging, and management (including organ preservation). Therapeutic options are explored, including surgery, radiotherapy, chemotherapy, and combined modality therapy. PMID:10918764

  7. Surgical correction of bladder neck contracture following prostate cancer treatment.

    PubMed

    Bugeja, Simon; Andrich, Daniela E; Mundy, Anthony R

    2014-01-01

    The surgical and non-surgical treatment of localised prostate cancer may be complicated by bladder neck contractures, prostatic urethral stenoses and bulbomembranous urethral strictures. In general, such complications following radical prostatectomy are less extensive, easier to treat and associated with a better outcome and more rapid recovery than the same complications following radiotherapy, high-intensity focussed ultrasound and cryotherapy. Treatment options range from minimally invasive endoscopic procedures to more complex and specialised open surgical reconstruction.In this chapter the surgical management of bladder neck contractures following the treatment of prostate cancer is described together with the management of prostatic urethral stenoses and bulbomembranous urethral strictures, given the difficulty in distinguishing them from one another clinically.

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

    PubMed

    Dong, Youhong; Wang, Anping

    2016-07-01

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

  9. [Neoadjuvant or Adjuvant Chemotherapy for Bladder Cancer?].

    PubMed

    Hupe, M C; Kramer, M W; Kuczyk, M A; Merseburger, A S

    2015-05-01

    Advanced urothelial carcinoma of the bladder is associated with a high metastatic potential. Life expectancy for metastatic patients is poor and rarely exceeds more than one year without further therapy. Neoadjuvant chemotherapy can decrease the tumour burden while reducing the risk of death. Adjuvant chemotherapy has been discussed controversially. Patients with lymph node-positive metastases seem to benefit the most from adjuvant chemotherapy. In selected patients, metastasectomy can prolong survival. In metastastic patients, the combination of gemcitabine and cisplatin has become the new standard regimen due to a lower toxicity in comparison to the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). For second-line treatment, vinflunine is the only approved therapeutic agent.

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

    PubMed

    Price, G E

    1994-03-01

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

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

    PubMed

    Skinner, Eila C

    2016-01-01

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

  12. Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology.

    PubMed

    Damrauer, Jeffrey S; Hoadley, Katherine A; Chism, David D; Fan, Cheng; Tiganelli, Christopher J; Wobker, Sara E; Yeh, Jen Jen; Milowsky, Matthew I; Iyer, Gopa; Parker, Joel S; Kim, William Y

    2014-02-25

    We sought to define whether there are intrinsic molecular subtypes of high-grade bladder cancer. Consensus clustering performed on gene expression data from a meta-dataset of high-grade, muscle-invasive bladder tumors identified two intrinsic, molecular subsets of high-grade bladder cancer, termed "luminal" and "basal-like," which have characteristics of different stages of urothelial differentiation, reflect the luminal and basal-like molecular subtypes of breast cancer, and have clinically meaningful differences in outcome. A gene set predictor, bladder cancer analysis of subtypes by gene expression (BASE47) was defined by prediction analysis of microarrays (PAM) and accurately classifies the subtypes. Our data demonstrate that there are at least two molecularly and clinically distinct subtypes of high-grade bladder cancer and validate the BASE47 as a subtype predictor. Future studies exploring the predictive value of the BASE47 subtypes for standard of care bladder cancer therapies, as well as novel subtype-specific therapies, will be of interest.

  13. Family history of cancer and the risk of bladder cancer: A case-control study from Italy.

    PubMed

    Turati, Federica; Bosetti, Cristina; Polesel, Jerry; Serraino, Diego; Montella, Maurizio; Libra, Massimo; Facchini, Gaetano; Ferraroni, Monica; Tavani, Alessandra; La Vecchia, Carlo; Negri, Eva

    2017-06-01

    A family history of bladder cancer has been associated with the risk of bladder cancer, but quantification of the excess risk in different populations is still a relevant issue. Further, the role of a family history of other cancers on the risk of bladder cancer remains unclear. We analyzed data from an Italian case-control study, including 690 bladder cancer cases and 665 hospital controls. Odds ratios (ORs) were estimated through unconditional logistic regression models, adjusted for sex, age, study center, year of interview and further for education, smoking and sibling's number. The OR for family history of bladder cancer was 2.13 (95% confidence intervals (95%CIs) 1.02-4.49) from the model with partial adjustment, and 1.99 (95%CI 0.91-4.32) after additional adjustment for smoking and siblings' number, based on 23 cases (3.3%) and 11 controls (1.7%) with a family history of bladder cancer. The fully adjusted OR was 3.77 when the relative was diagnosed at age below 65years. Smokers with a family history of bladder cancer had a four-fold increased risk compared to non-smokers without a family history. Bladder cancer risk was significantly increased among subjects with a family history of hemolymphopoietic cancers (OR=2.97, 95%CI 1.35-6.55). Family history of cancer at other sites showed no significant association with bladder cancer risk. This study confirms an approximately two-fold increased risk of bladder cancer for family history of bladder cancer, and indicates a possible familial clustering of bladder cancer with cancers of the hemolymphopoietic system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. 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

    2017-08-31

    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.

  15. Neoadjuvant and adjuvant chemotherapy approaches for invasive bladder cancer.

    PubMed

    Raghavan, Derek; Burgess, Earle; Gaston, Kris E; Haake, Michael R; Riggs, Steven B

    2012-10-01

    Deeply invasive bladder cancer, representing approximately 20% of incident cases, is cured by radical cystectomy or radiotherapy in less than 50% of cases. In an effort to improve cure rates, based on objective response rates in metastatic disease of 40%-70% from combination chemotherapy regimens, systemic chemotherapy has been incorporated into programs of definitive treatment for this disease. Several randomized trials and a meta-analysis have confirmed a survival benefit from neoadjuvant chemotherapy followed by definitive local treatment, reflecting both median survival figures and cure rates. Despite several promising phase II trials, no randomized trial of classical adjuvant chemotherapy for bladder cancer has demonstrated an overall survival benefit, despite increments in disease-free survival. Molecular prognostication has been studied in an effort to improve the utility of systemic therapy for invasive non-metastatic bladder cancer, but randomized trials have not shown associated survival benefit. Despite level 1 evidence of a survival benefit from neoadjuvant MVAC (methotrexate, vinblastine, doxorubicin [Adriamycin], cisplatin) or cisplatin, methotrexate, and vinblastine (CMV) chemotherapy, more than 50% of incident cases do not receive such treatment.

  16. Pesticide, Gene Polymorphisms and Bladder Cancer among Egyptian Agricultural Workers

    PubMed Central

    Amr, Sania; Dawson, Rebecca; Saleh, Doa’a A.; Magder, Laurence S.; St. George, Diane Marie; El-Daly, Mai; Squibb, Katherine; Mikhail, Nabiel N.; Abdel-Hamid, Mohamed; Khaled, Hussein; Loffredo, Christopher A.

    2013-01-01

    We examined the associations between pesticide exposure, genetic polymorphisms for NAD(P)H:quinone oxidoreductase I (NQO1) and superoxide dismutase 2 (SOD2), and urinary bladder cancer risk among male agricultural workers in Egypt. We used logistic regression to analyze data from a multi-center case-control study and estimate adjusted odds ratio (OR) and 95% CI (confidence interval) Exposure to pesticides was associated with increased bladder cancer risk (1.68 (1.23–2.29)) in a dose-dependent manner. The association was slightly stronger for urothelial (1.79 (1.25–2.56) than for squamous cell carcinoma (1.55 (1.03–2.31)), and among participants with combined genotypes for low NQO1 and high SOD2 (2.14 (1.19–3.85) activities as compared to those with high NQO1 and low SOD2 genotypes (1.53 (0.73–3.25)). In conclusion, among male agricultural workers in Egypt, pesticide exposure is associated with bladder cancer risk and possibly modulated by genetic polymorphism. PMID:24219772

  17. Pioglitazone use and the risk of bladder cancer.

    PubMed

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

    2014-02-01

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

  18. Bladder tumour antigen (BTA stat) test compared to the urine cytology in the diagnosis of bladder cancer: A meta-analysis.

    PubMed

    Guo, Aiye; Wang, Xiuhua; Gao, Lan; Shi, Juan; Sun, Changyi; Wan, Zhen

    2014-05-01

    We evaluate the diagnostic value of bladder tumour antigen (BTA stat) tests compared with urine cytology test in detecting bladder cancer. We searched public databases including PubMed, MEDLINE Springer, Elsevier Science Direct, Cochrane Library and Google Scholar before December 2012. To collect relevant data of BTA stat tests and urine cytology tests in patients with bladder cancer, we studied meta-analyses of sensitivity, specificity, positive likelihood ratio (LR), negative LR and diagnostic odds ratios (DOR) of BTA stat tests and cytology tests from published studies. We applied the software of Rev. Man 5.1 and Stata 11.0 to the meta-analysis. A total of 13 separate studies consisting of 3462 patients with bladder cancer were considered in the meta-analysis. We found that the BTA stat test had a higher sensitivity than the urine cytology test (0.67, 95% confidence interval [CI] 0.64 to 0.69 vs. 0.43, 95% CI 0.40 to 0.46), but the specificity, positive LR, negative LR, DOR, the area under the curve (AUC) and Q index of the BTA stat test were lower compared with the urine cytology test. The results of the Egger's linear regression test showed no publication bias (p > 0.05). Specificity, positive LR, negative LR, DOR, the AUC and the Q index of the urine cytology test may be superior to the BTA stat test, but the BTA stat test has greater sensitivity than the urine cytology test.

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

    SciTech Connect

    Coen, John J.; Paly, Jonathan J.; Niemierko, Andrzej; Kaufman, Donald S.; Heney, Niall M.; Spiegel, Daphne Y.; Efstathiou, Jason A.; Zietman, Anthony L.; Shipley, William U.

    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. Patients 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.

  20. Early detection of dysplasia in colon and bladder tissue using laser-induced fluorescence

    NASA Astrophysics Data System (ADS)

    Rava, Richard P.; Richards-Kortum, Rebecca R.; Fitzmaurice, Maryann; Cothren, Robert M., Jr.; Petras, Robert; Sivak, Michael J., Jr.; Levine, Howard H.

    1991-06-01

    Laser induced fluorescence has been explored as an early detection scheme for two clinically important examples of neoplasia: colorectal dysplasia and transitional cell carcinoma in the urinary bladder. In both, it is desirable to detect microscopic and biochemical changes of pre-cancer in order to identify patients at risk for developing invasive carcinoma. This paper will compare the fluorescence obtained from these two pre-cancerous conditions, and discuss the connection between the fluorescence and the morphological/molecular changes occurring in the tissue. The similarities and differences in the fluorescence will be compared to determine the general features of pre-cancerous changes that might be utilized for detection of the disease.

  1. Quantitative glycome analysis of N-glycan patterns in bladder cancer vs normal bladder cells using an integrated strategy.

    PubMed

    Yang, Ganglong; Tan, Zengqi; Lu, Wei; Guo, Jia; Yu, Hanjie; Yu, Jingmin; Sun, Chengwen; Qi, Xiaowei; Li, Zheng; Guan, Feng

    2015-02-06

    Diagnosis of bladder cancer, one of the most common types of human cancer, at an early (nonmuscle-invasive) stage is the best way to reduce the mortality rate. Tumor malignancy in general is closely associated with alterations of glycan expression. Glycosylation status, particularly global glycomes, in bladder cancer has not been well studied. We integrated lectin microarray and mass spectrometry (MS) methods to quantitatively analyze and compare glycan expression in four bladder cancer cell lines (KK47, YTS1, J82, T24) and one normal bladder mucosa cell line (HCV29). Glycopattern alterations were analyzed using lectin microarray analysis and confirmed by lectin staining and lectin blotting. Associations of glycopatterns with diverging stages were evaluated by lectin histochemistry on tissue microarrays. N-Glycans were derivatized by amidation of sialylated glycans with acetohydrazide and reductive amination with the stable isotope tags [(12)C6]- and [(13)C6]-aniline, and were quantitatively analyzed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). N-Glycan biosynthesis-associated proteins were quantitatively analyzed by a stable isotope labeling by amino acids in cell culture (SILAC) proteomics method, which revealed significant differences in expression of 13 glycosyltransferases and 4 glycosidases. Our findings indicate that sialyl Lewis X (sLe(x)), terminal GalNAc and Gal, and high mannose-type N-glycans were more highly expressed in bladder cancer cells and tissues than in normal cells. Bladder cancer cells showed high expression of core-fucosylated N-glycans but low expression of terminally fucosylated N-glycans. Each of these glycome changes may be directly related to bladder cancer progression.

  2. Immunotherapy of murine bladder cancer by irradiated tumor vaccine

    SciTech Connect

    Lamm, D.L.; Riggs, D.R.; DeHaven, J.I.; Bryner, R.W. )

    1991-01-01

    This investigation explored the efficacy of irradiated autologous mouse bladder tumor (Ir-MBT2) as an active specific immunotherapeutic agent and as adjuvant therapy with Bacillus Calmette-Guerin (BCG) against a subcutaneously transplanted murine bladder tumor. Tumor incidence was significantly reduced in groups receiving BCG (27%, p less than 0.005) or Ir-MBT2 with BCG (53%, p less than 0.025), compared to control (93%). Survival was significantly improved in groups treated with BCG (100%, p less than 0.005), 10(5) Ir-MBT2 with BCG (53%, p less than 0.01), or 10(7) Ir-MBT2 with BCG (47%, p less than 0.025) compared with control (13%). Surprisingly, Ir-MBT2 consistently reduced the efficacy of BCG alone. Ir-MBT2 alone (10(7)) appeared to enhance tumor growth. Autologous irradiated bladder tumor vaccine, alone or in combination with BCG, displayed no immunotherapeutic advantage. The use of irradiated tumor cell vaccine for bladder cancer therapy may reduce the results achievable with BCG alone.

  3. Intraoperative radiation therapy in patients with bladder cancer. A review of techniques allowing improved tumor doses and providing high cure rates without loss of bladder function

    SciTech Connect

    Shipley, W.U.; Kaufman, S.D.; Prout, G.R. Jr.

    1987-10-01

    Conventional external beam irradiation, using modern megavoltage techniques and doses that do not harm bladder function, will permanently eradicate local bladder cancer in 30% to 50% of patients, compared with 70% to 90% with cystectomy. In appropriately chosen patients, open surgery can safely provide excellent exposure for the selective delivery of more radiant energy directly to the tumor and less to the uninvolved portion of the bladder. Intraoperative radiation therapy, by either a removable radium or iridium implant or a large single dose of electrons, has been reported to be safe and can permanently cure the bladder of cancer and also preserve bladder function in more than 75% of patients with solitary tumors that invade into but not beyond the bladder muscle. With the increasing interest in and availability of intraoperative radiation therapy in the US, this curative and bladder-sparing treatment for operable patients with bladder cancer invading the trigone is appropriate for careful clinical trial. 13 references.

  4. Determination of the differential expression of mitochondrial long non-coding RNAs as a noninvasive diagnosis of bladder cancer

    PubMed Central

    2012-01-01

    Background Bladder cancer is a significant cause of morbidity and mortality with a high recurrence rate. Early detection of bladder cancer is essential in order to remove the tumor, to preserve the organ and to avoid metastasis. The aim of this study was to analyze the differential expression of mitochondrial non-coding RNAs (sense and antisense) in cells isolated from voided urine of patients with bladder cancer as a noninvasive diagnostic assay. Methods The differential expression of the sense (SncmtRNA) and the antisense (ASncmtRNAs) transcripts in cells isolated from voided urine was determined by fluorescent in situ hybridization. The test uses a multiprobe mixture labeled with different fluorophores and takes about 1 hour to complete. We examined the expression of these transcripts in cells isolated from urine of 24 patients with bladder cancer and from 15 healthy donors. Results This study indicates that the SncmtRNA and the ASncmtRNAs are stable in cells present in urine. The test reveals that the expression pattern of the mitochondrial transcripts can discriminate between normal and tumor cells. The analysis of 24 urine samples from patients with bladder cancer revealed expression of the SncmtRNA and down-regulation of the ASncmtRNAs. Exfoliated cells recovered from the urine of healthy donors do not express these mitochondrial transcripts. This is the first report showing that the differential expression of these mitochondrial transcripts can detect tumor cells in the urine of patients with low and high grade bladder cancer. Conclusion This pilot study indicates that fluorescent in situ hybridization of cells from urine of patients with different grades of bladder cancer confirmed the tumor origin of these cells. Samples from the 24 patients with bladder cancer contain cells that express the SncmtRNA and down-regulate the ASncmtRNAs. In contrast, the hybridization of the few exfoliated cells recovered from healthy donors revealed no expression of these

  5. Failure of ascorbic acid to inhibit FANFT-induced bladder cancer.

    PubMed

    Soloway, M S; Cohen, S M; Dekernion, J B; Persky, L

    1975-04-01

    L-ascorbic acid has been shown to reduce the elevated level of urinary chemiluminescence found in patients with bladder cancer. Thus, it has been suggested that vitamin C might be efficacious in bladder tumor prophylaxis. However, there is no clinical evidence to support this thesis. We evaluated whether L-ascorbic acid given concomitantly with the urinary carcinogen FANFT was capable of reducing the incidence of subsequent bladder tumors. No inhibitory effect was observed. Unless evidence is obtained demonstrating bladder tumor prevention by L-ascorbic acid its routine administration to patients with bladder cancer is not indicated.

  6. Mouse Models of Human Bladder Cancer as a Tool for Drug Discovery

    PubMed Central

    Seager, Catherine; Puzio-Kuter, Anna M.; Cordon-Cardo, Carlos; McKiernan, James; Abate-Shen, Cory

    2010-01-01

    Muscle-invasive bladder cancer is a deadly condition in dire need of effective new treatments. This unit contains a description of mouse models suitable for the evaluation of potential new therapies. Included is a genetically engineered mouse model of bladder cancer generated by the delivery of an adenovirus expressing Cre recombinase into the bladder lumen. Also described is an orthotopic mouse model created by the instillation of human bladder tumor cells into the bladder lumen of immune deficient mice. Protocols are also provided on the use of these models for the preclinical evaluation of new chemical entities, with mTOR inhibitors shown as an example. PMID:22294368

  7. Interobserver Agreement of Confocal Laser Endomicroscopy for Bladder Cancer

    PubMed Central

    Chang, Timothy C.; Liu, Jen-Jane; Hsiao, Shelly T.; Pan, Ying; Mach, Kathleen E.; Leppert, John T.; McKenney, Jesse K.; Rouse, Robert V.

    2013-01-01

    Abstract Background and Purpose Emerging optical imaging technologies such as confocal laser endomicroscopy (CLE) hold promise in improving bladder cancer diagnosis. The purpose of this study was to determine the interobserver agreement of image interpretation using CLE for bladder cancer. Methods Experienced CLE urologists (n=2), novice CLE urologists (n=6), pathologists (n=4), and nonclinical researchers (n=5) were recruited to participate in a 2-hour computer-based training consisting of a teaching and validation set of intraoperative white light cystoscopy (WLC) and CLE video sequences from patients undergoing transurethral resection of bladder tumor. Interobserver agreement was determined using the κ statistic. Results Of the 31 bladder regions analyzed, 19 were cancer and 12 were benign. For cancer diagnosis, experienced CLE urologists had substantial agreement for both CLE and WLC+CLE (90%, κ 0.80) compared with moderate agreement for WLC alone (74%, κ 0.46), while novice CLE urologists had moderate agreement for CLE (77%, κ 0.55), WLC (78%, κ 0.54), and WLC+CLE (80%, κ 0.59). Pathologists had substantial agreement for CLE (81%, κ 0.61), and nonclinical researchers had moderate agreement (77%, κ 0.49) in cancer diagnosis. For cancer grading, experienced CLE urologists had fair to moderate agreement for CLE (68%, κ 0.64), WLC (74%, κ 0.67), and WLC+CLE (53%, κ 0.33), as did novice CLE urologists for CLE (53%, κ 0.39), WLC (66%, κ 0.50), and WLC+CLE (61%, κ 0.49). Pathologists (65%, κ 0.55) and nonclinical researchers (61%, κ 0.56) both had moderate agreement for CLE in cancer grading. Conclusions CLE is an adoptable technology for cancer diagnosis in novice CLE observers after a short training with moderate interobserver agreement and diagnostic accuracy similar to WLC alone. Experienced CLE observers may be capable of achieving substantial levels of agreement for cancer diagnosis that is higher than with WLC alone. PMID:23072435

  8. 5-Aminolevulinic acid-mediated photodynamic therapy for bladder cancer.

    PubMed

    Inoue, Keiji

    2017-02-01

    Photodynamic therapy using 5-aminolevulinic acid is a treatment method in which the fluorescent substance of protoporphyrin IX excessively accumulated specifically in cancer cells is excited by visible red or green light irradiation, and reactive oxygen is produced and injures cancer cells. Photodynamic therapy using 5-aminolevulinic acid less markedly influences the surrounding normal cells and tissue as a result of no accumulation of protoporphyrin IX, being a low-invasive, less harmful treatment localized to cancer. Furthermore, photodynamic therapy using 5-aminolevulinic acid is painless, requiring no anesthesia because localized lesions are treated at a low-energy level, and repeatedly applicable, unlike radiotherapy, and so is expected to be a new low-invasive treatment based on a concept completely different from existing treatments. In fact, photodynamic therapy using 5-aminolevulinic acid for bladder cancer was clinically demonstrated mainly for treatment-resistant bladder carcinoma in situ, and favorable outcomes have been obtained. Photodynamic therapy using 5-aminolevulinic acid are photodynamic technologies based on the common biological characteristic of cancers, and are expected as novel therapeutic strategies for many types of cancer. © 2017 The Japanese Urological Association.

  9. [Cancer procoagulant and cathepsin D activity in blood serum in patients with bladder cancer].

    PubMed

    Szajda, Sławomir Dariusz; Darewicz, Barbara; Kudelski, Jacek; Chlabicz, Marcin; Domel, Tomasz; Chabielska, Ewa; Skrzydlewski, Zdzisław

    2005-06-01

    The increasing morbidity and mortality rates of bladder cancer forced the scientists to search for new unfailing diagnostic and therapeutic methods that will improve treatment effects. There are biochemical cancer markers as cancer procoagulant (CP) and cathepsin D which may be used to this end. The aim of the study was to evaluate the activity of the cancer procoagulant and cathepsin D in the blood serum in patients with superficial bladder cancer. The venous blood samples were from 15 patients with microscopically proved superficial bladder carcinoma (i.e. study group) and 15 normal volunteers as a control group. The serum blood CP activity was determined by the Gordon-Benson's coagulation method and expressed by the clotting time in seconds (s) while the cathepsin D activity was determined by the Folin-Ciocalteau's method and expressed by a quantity of released tyrosine in nmol/ml per 4 hours. The CP activity in serum of patients with superficial bladder cancer was increased in statistically way as compared to the non-cancer controls (p<0.0001). The cathepsin D activity in blood serum of the study group was also enhanced as compared to the control group and the said values differed statistically (p<0.0351). It appears to be justifiable to apply the determination of the CP and cathepsin D activity in blood serum for the diagnostics of superficial bladder cancer.

  10. Cross-species analysis of the canine and human bladder cancer transcriptome and exome.

    PubMed

    Ramsey, Stephen A; Xu, Tanjin; Goodall, Cheri; Rhodes, Adelaide C; Kashyap, Amita; He, Jun; Bracha, Shay

    2017-04-01

    We investigated the correspondence between transcriptome and exome alterations in canine bladder cancer and the correspondence between these alterations and cancer-driving genes and transcriptional alterations in human bladder cancer. We profiled canine bladder tumors using mRNA-seq and exome-seq in order to investigate the similarity of transcriptional alterations in bladder cancer, in humans and canines, at the levels of gene functions, pathways, and cytogenetic regions. We found that the transcriptomes of canine and human bladder cancer are remarkably similar at the functional and pathway levels. We demonstrated that canine bladder cancer involves coordinated differential expression of genes within cytogenetic bands, and that these patterns are consistent with those seen in human bladder cancer. We found that genes that are mutated in canine bladder cancer are more likely to be transcriptionally downregulated than non-mutated genes, in the tumor. Finally we report three novel mutations (FAM133B, RAB3GAP2, and ANKRD52) for canine bladder cancer.

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

    PubMed

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

    2013-02-01

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

  12. The expression of p63 in bladder cancer vs. chronic bilharzial bladder.

    PubMed

    Mursi, Khaled; Agag, Ayman; Hammam, Olfat; Riad, Mahmoud; Daw, Mahmoud

    2013-03-01

    To investigate the immunohistochemical expression of p63 in bladder cancer and the variation of expression in relation to histological type, grade and stage of the tumour, and whether bilharziasis (endemic in Egypt) has an effect on its expression, in an attempt to better understand the tumour behaviour and the possibility of using p63 as a prognostic marker. In a prospective study, biopsies were taken from the bladders of 70 patients, who were divided into three groups; group A comprised 10 with a normal urothelium, group B comprised 20 with chronic cystitis (bilharzial and non-bilharzial) and group C contained 40 with bladder cancer. The biopsies were examined for the expression of p63, using immunohistochemical techniques. The mean (SD) ages of groups A, B and C were 45.2 (9.5), 50.5 (11.7) and 60.5 (9.9) years, respectively. There was a statistically significant decrease in the expression and immunoreactivity in group C (P < 0.05), and a significant decrease with advancing tumour stage and grade (P < 0.01). In cases of squamous cell carcinoma there was a statistically significant lower immunoreactivity than in transitional cell carcinoma (P < 0.05). There was a tendency for a statistically significant decrease in the immunoreactivity in bilharzial cystitis (P < 0.05), but in the malignant group, bilharziasis had no apparent effect on the pattern of expression. p63 might be a helpful biomarker and adjunct in predicting the biological behaviour and progression of tumours. Further studies are recommended to elucidate more clearly its role as a prognostic indicator and its utility as a tumour marker.

  13. Diagnostic Value of Urine Cytology in Bladder Cancer. A Meta-Analysis.

    PubMed

    Xie, Qingnan; Huang, Zhen; Zhu, Zhiqiang; Zheng, Xin; Liu, Jianwei; Zhang, Mengmeng; Zhang, Yu

    2016-02-01

    To evaluate the diagnostic value of urine cytology in detecting bladder cancer using meta-analysis. Public databases, including PubMed, Embase, Springer, Elsevier Science Direct, Cochrane Library, and Google Scholar, were searched before February 2015. Sensitivity, specificity, positive likelihood ratio (LR), negative LR, and diagnostic odds ratio (DOR) of urine cytology in individual studies were calculated using random effects model or fixed effect model. The summary receiver operating characteristic (SROC) curve was applied for performance of urine cytology. Publication bias of the included studies was evaluated by Egger's test. A total of 17 separate studies consisting of 5,908 patients with bladder cancer were included in the meta-analysis. Significant heterogeneity between the studies (I2 = 98.6%, p < 0.01) and effect sizes were pooled using random effects model. Overall sensitivity, specificity, positive LR, negative LR, and DOR of urine cytology were 0.37 (95% CI 0.35-0.39), 0.95 (95% CI 0.94-0.95), 7.39 (95% CI 4.97-10.98), 0.56 (95% CI 0.47-0.68), and 15.76 (95% CI 9.03-27.50), respectively. The area under the curve (AUC) and Q* index were 0.80 and 0.74, respectively. No publication bias was observed (p = 0.12). Our data indicate that urine cytology might be more suitable as an assistant method in bladder cancer detection by combining with other diagnostic methods with high sensitivity.

  14. TERT Core Promotor Mutations in Early-Onset Bladder Cancer

    PubMed Central

    Giedl, Johannes; Rogler, Anja; Wild, Andreas; Riener, Marc-Oliver; Filbeck, Thomas; Burger, Maximilian; Rümmele, Petra; Hurst, Carolyn; Knowles, Margaret; Hartmann, Arndt; Zinnall, Ulrike; Stoehr, Robert

    2016-01-01

    Activating mutations in the core promoter of the TERT gene have been described in many different tumor entities. In vitro models showed a two- to fourfold increase in transcriptional activity of the TERT promoter through creation of a consensus binding motif for Ets/TCF transcription factors caused by these mutations. TERT core promoter mutations are the most common mutations in bladder cancer with a frequency between 55.6% and 82.8% described so far, and are independent of stage and grade. Since limited data on molecular alterations of early-onset bladder tumors exists, we assessed the frequency of TERT core promoter mutations in early-onset bladder cancer. Two cohorts of bladder tumors (early-onset patient group; n=144 (age of onset of disease ≤45 years); unselected, consecutive group; n=125) were examined for TERT core promoter mutations. After microdissection and extraction of DNA the corresponding hotspot regions in the TERT core promoter were examined by Sanger-sequencing or a SNaPshot approach. A significantly lower frequency of TERT core promoter mutations was found in tumors from the early-onset cohort compared to the consecutive cohort (57.6% vs. 84.8%, p<0.001). Among the early-onset cohort cases younger than the cohort's median age of 39 years at disease onset showed a significantly reduced number of TERT promoter mutations (31/67, 46,3%) than cases aged between 39 and 45 years (52/77, 67.5%; p=0.012). This association was not found in the consecutive cases. Mutation status was independent of tumor stage and grade. We conclude that in tumors from early-onset bladder cancer patients TERT core promoter mutations are not as frequent as in bladder tumors from consecutive cases, but seem to play an important role there as well. In patients below 39 years of age TERT core promoter mutations are a more infrequent event, suggesting different mechanisms of tumorigenesis in these young patients. PMID:27313781

  15. Intensity modulated radiotherapy for elderly bladder cancer patients

    PubMed Central

    2011-01-01

    Background To review our experience and evaluate treatment planning using intensity-modulated radiotherapy (IMRT) and helical tomotherapy (HT) for the treatment of elderly patients with bladder cancer. Methods From November 2006 through November 2009, we enrolled 19 elderly patients with histologically confirmed bladder cancer, 9 in the IMRT and 10 in the HT group. The patients received 64.8 Gy to the bladder with or without concurrent chemotherapy. Conventional 4-field "box" pelvic radiation therapy (2DRT) plans were generated for comparison. Results The median patient age was 80 years old (range, 65-90 years old). The median survival was 21 months (5 to 26 months). The actuarial 2-year overall survival (OS) for the IMRT vs. the HT group was 26.3% vs .37.5%, respectively; the corresponding values for disease-free survival were 58.3% vs. 83.3%, respectively; for locoregional progression-free survival (LRPFS), the values were 87.5% vs. 83.3%, respectively; and for metastases-free survival, the values were 66.7% vs. 60.0%, respectively. The 2-year OS rates for T1, 2 vs. T3, 4 were 66.7% vs. 35.4%, respectively (p = 0.046). The 2-year OS rate was poor for those whose RT completion time greater than 8 weeks when compared with the RT completed within 8 wks (37.9% vs. 0%, p = 0.004). Conclusion IMRT and HT provide good LRPFS with tolerable toxicity for elderly patients with invasive bladder cancer. IMRT and HT dosimetry and organ sparing capability were superior to that of 2DRT, and HT provides better sparing ability than IMRT. The T category and the RT completion time influence OS rate. PMID:21679408

  16. Concurrence of villous adenoma and non-muscle invasive bladder cancer arising in the bladder: a case report and review of the literature

    PubMed Central

    2013-01-01

    Background Villous adenoma arising in the urinary tract is rare tumor. Most cases have been identified as benign neoplasm in the colon. Villous adenoma of the gastrointestinal tract is thought arise from premalignant polyps. Here, we report a case of concurrence of villous adenoma and non-muscle invasive bladder cancer. Case presentation An 85-year-old woman presented at our office because of gross hematuria. Cystoscopic examination detected two papillary tumors in the bladder. Each tumor was resected and diagnosed, respectively. Histopathology confirmed that the resected one tumor was a villous adenoma, and the other was urothelial carcinoma (T1, high grade). Immunostaining for cytokeratin (CK) 7, CK20 and Ki-67 confirmed that CK7: (−), CK20: (+) and Ki-67: (<=30%) in villous adenoma while CK7: (+), CK20: (+), and Ki-67: (70%) in urothelial carcinoma. Three months later from TUR, urothelial carcinoma recurred in the trigone. She received adjuvant intravesical immunotherapy with BCG post TUR for the recurrence site. Conclusion There were no specific findings on ultrasonography, CT, MRI or cystoscopic examination morphologically. Therefore, pre-pathological villous adenoma of the bladder is extremely difficult to diagnose. There are some case reports of solitary villous adenoma in the bladder or with coexisting adeno carcinoma. However, to the best of our knowledge, this is only the second report of villous adenoma in the bladder of coexisting urothelial carcinoma that has been published in the literature. Premalignant villous adenoma of the bladder is extremely rare and difficult to diagnose without histologic examination. Any suspicious lesion of the bladder should be biopsied and/or resected to confirm histology. PMID:23870731

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

    SciTech Connect

    Zhu, Hongxue; Li, Xuechao; Song, Yarong; Zhang, Peng; Xiao, Yajun; Xing, Yifei

    2015-11-13

    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 cell 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.

  18. Nitrate in drinking water and bladder cancer risk in Spain.

    PubMed

    Espejo-Herrera, Nadia; Cantor, Kenneth P; Malats, Nuria; Silverman, Debra T; Tardón, Adonina; García-Closas, Reina; Serra, Consol; Kogevinas, Manolis; Villanueva, Cristina M

    2015-02-01

    Nitrate is a widespread contaminant in drinking water and ingested nitrate under conditions resulting in endogenous nitrosation is suspected to be carcinogenic. However, the suggested association between nitrate in drinking water and bladder cancer remains inconsistent. We evaluated the long-term exposure to drinking water nitrate as a risk factor for bladder cancer, considering endogenous nitrosation modifiers and other covariables. We conducted a hospital-based case-control study of bladder cancer in Spain (1998-2001). Residential histories and water consumption information were ascertained through personal interviews. Historical nitrate levels (1940-2000) were estimated in study municipalities based on monitoring records and water source. Residential histories of study subjects were linked with nitrate estimates by year and municipality to calculate individual exposure from age 18 to recruitment. We calculated odds ratios (OR) and 95% confidence intervals (CI) for bladder cancer among 531 cases and 556 controls with reliable interviews and nitrate exposure information covering at least 70% of years from age 18 to interview. Average residential levels ranged from 2.1mg/L to 12.0mg/L among regions. Adjusted OR (95%CI) for average residential levels relative to ≤ 5 mg/L were 1.2 (0.7-2.0) for >5-10mg/L and 1.1 (0.6-1.9) for >10mg/L. The OR for subjects with longest exposure duration (>20 years) to highest levels (>9.5mg/L) was 1.4 (0.9-2.3). Stratification by intake of vitamin C, vitamin E, meat, and gastric ulcer diagnosis did not modify these results. A non-significant negative association was found with waterborne ingested nitrate with an OR of 0.7 (0.4-1.0) for >8 vs. ≤ 4 mg/day. Adjustment for several covariables showed similar results to crude analyses. Bladder cancer risk was inconsistently associated with chronic exposure to drinking water nitrate at levels below the current regulatory limit. Elevated risk is suggested only among subjects with longest

  19. 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

  20. Fluid intake and risk of bladder cancer in the Nurses' Health Studies.

    PubMed

    Zhou, Jiachen; Kelsey, Karl T; Giovannucci, Edward; Michaud, Dominique S

    2014-09-01

    Increase in fluid intake may reduce bladder cancer risk by decreasing the contact time between carcinogens in urine and bladder epithelium. However, this association has not been examined in a large cohort of women. The association between total fluid intake and bladder cancer risk in two large prospective women's cohorts with 427 incident bladder cancer cases was examined. Detailed information on total fluid intake was collected by repeated food frequency questionnaires over time. Multivariable relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated by using Cox proportional hazards regression models. Results from the two cohorts were pooled together using the random-effects model. Using the average values from the earliest two dietary assessments and lowest quartile as reference, a suggestive inverse association was observed between total fluid intake and overall bladder cancer risk (RR: 0.83, 95% CI: 0.61-1.12, p-value for trend: 0.08), and invasive bladder cancer risk (RR: 0.47, 95% CI: 0.23-0.97, p-value for trend: 0.04). Among heavy cigarette smokers, women with the highest quartile of total fluid intake had a 38% decrease in bladder cancer risk (RR: 0.62, 95% CI: 0.41-0.93, p-value for trend: 0.02). The findings suggested that total fluid intake may reduce bladder cancer risk for female smokers, as well as reduce the risk of invasive bladder cancer. © 2014 UICC.

  1. Does phosphorylation of cofilin affect the progression of human bladder cancer?

    PubMed

    Chung, Hong; Kim, Bokyung; Jung, Seung-Hyo; Won, Kyung-Jong; Jiang, Xiaowen; Lee, Chang-Kwon; Lim, So Dug; Yang, Sang-Kuk; Song, Ki Hak; Kim, Hong Sup

    2013-02-01

    We determined the differently expressed protein profiles and their functions in bladder cancer tissues with the aim of identifying possible target proteins and underlying molecular mechanisms for taking part in their progression. We examined the expression of proteins by proteomic analysis and western blot in normal urothelium, non-muscle-invasive bladder cancers (NMIBCs), and muscle-invasive bladder cancers (MIBCs). The function of cofilin was analyzed using T24 human bladder cancer cells. The expression levels of 12 proteins were altered between bladder cancers and normal bladder tissues. Of these proteins, 14-3-3σ was upregulated in both NMIBCs and MIBCs compared with controls. On the other hand, myosin regulatory light chain 2, galectin-1, lipid-binding AI, annexin V, transthyretin, CARD-inhibitor of NF-κB-activating ligand, and actin prepeptide were downregulated in cancer samples. Cofilin, an actin-depolymerizing factor, was prominent in both NMIBCs and MIBCs compared with normal bladder tissues. Furthermore, we confirmed that cofilin phosphorylation was more prominent in MIBCs than in NMIBCs using immunoblotting and immunohistochemcal analyses. Epidermal growth factor (EGF) increased the phosphorylation of cofilin and elevated the migration in T24 cells. Knockdown of cofilin expression with small interfering RNA attenuated the T24 cell migration in response to EGF. These results demonstrate that the increased expression and phosphorylation of cofilin might play a role in the occurrence and invasiveness of bladder cancer. We suspected that changes in cofilin expression may participate in the progression of the bladder cancer.

  2. Fluid intake and risk of bladder cancer in the Nurses’ Health Studies

    PubMed Central

    Zhou, Jiachen; Kelsey, Karl T.; Giovannucci, Edward; Michaud, Dominique S.

    2014-01-01

    Increase in fluid intake may reduce bladder cancer risk by decreasing the contact time between carcinogens in urine and bladder epithelium. However, this association has not been examined in a large cohort of women. We examined the association between total fluid intake and bladder cancer risk in two large prospective women's cohorts with 427 incident bladder cancer cases. Detailed information on total fluid intake was collected by repeated food frequency questionnaires over time. Multivariable relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated by using Cox proportional hazards regression models. Results from the two cohorts were pooled together using the random-effects model. Using the average values from the earliest two dietary assessments and lowest quartile as reference, a suggestive inverse association was observed between total fluid intake and overall bladder cancer risk (RR: 0.83, 95% CI: 0.61-1.12, p-value for trend: 0.08), and invasive bladder cancer risk (RR: 0.47, 95% CI: 0.23-0.97, p-value for trend: 0.04). Among heavy cigarette smokers, women with the highest quartile of total fluid intake had a 38% decrease in bladder cancer risk (RR: 0.62, 95% CI: 0.41-0.93, p-value for trend: 0.02). Our findings suggest that total fluid intake may reduce bladder cancer risk for female smokers, as well as reduce the risk of invasive bladder cancer. PMID:24500943

  3. [Bladder cancer screening with urine-based tumour markers - occupational medical experience].

    PubMed

    Nasterlack, M; Feil, G; Leng, G; Pesch, B; Huber, S; Sievert, K-D; Johnen, G; Taeger, D; Mayer, T; Kluckert, M; Brüning, T; Stenzl, A

    2011-03-01

    Bladder cancer responds favourably to treatment and has a good survival rate, provided it is diagnosed at an early stage. Established methods exist for the early detection, however, their specificity and positive predictive value are not yet satisfactory. Innovative markers have been proposed, but still require validation in prospective studies. We provide a literature-based short overview on the currently available and some proposed markers for the early detection of bladder cancer and evaluate the need for validation in further studies. We further provide some first results of such a recently finished study in an occupational setting. We conducted a prospective screening study over seven years in 1610 males with former occupational exposure to carcinogenic aromatic amines. Annual bladder cancer screening according to statutory requirements was offered. In addition to the regularly performed check for hematuria and urine cytology, the markers NMP22, UroVysion™ and survivin were performed in voided urine samples of the participants. Positive findings (not for survivin) were further followed through urethrocystoscopy. A total of 7219 urine samples were screened. During the study period 16 incidental and 4 recurrent bladder tumours, thereof three papillomas, occurred in a total of 19 participants. 14 out of twenty tumours were marker-positive, and all but two were early stage findings. Cell-based markers (cytology, UroVysion™) und molecular markers (NMP22, survivin) were largely complementary, thus acting as a "multi-marker panel". Eight of the tumours were identified by a positive cytology. Six tumours were not detected by any of the tumour markers. The results will be further evaluated through the inclusion of confounding factors, which have so far rarely been examined in other studies. This may lead to the development of tiered diagnostic strategies with the aim to reduce the number of invasive diagnostic procedures in the future. © Georg Thieme Verlag KG

  4. Sentinel lymph node biopsy in bladder cancer: Systematic review and technology update

    PubMed Central

    Liss, Michael A.; Noguchi, Jonathan; Lee, Hak J.; Vera, David R.; Kader, A. Karim

    2015-01-01

    A sentinel lymph node (SLN) is the first lymph node to drain a solid tumor and likely the first place metastasis will travel. SLN biopsy has been well established as a staging tool for melanoma and breast cancer to guide lymph node dissection (LND); its utility in bladder cancer is debated. We performed a systematic search of PubMed for both human and animal studies that looked at SLN detection in cases of urothelial carcinoma of the bladder. We identified a total of nine studies that assessed a variety of imaging techniques to identify SLNs in patients with urothelial carcinoma of the bladder. Eight studies investigated human patients while one looked at animal (dog) models. Seven studies representing 156 patients noted the negative predictive value of the SLN to predict a metastasis free state was 92% (92/100). The SLN biopsy was less accurate in metastatic patients with a positive predictive value of only 77% (43/56) with a false negative range of in individual studies of 0-19%. Clinically, positive nodes routinely do not take up the pharmaceutical agent for SLN. Therefore, SLN biopsy is a promising concept with a 92% negative predictive value; however, the false negative rates are high which may be improved by standardizing populations and indications. Novel technologies are improving the detection of SLN and may provide the surgeon with an improved ability to detect micrometastasis, guide surgery, and reduce patient morbidity. PMID:26166959

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

    PubMed

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

    2016-09-01

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

  6. Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance

    PubMed Central

    Kurtova, Antonina V.; Xiao, Jing; Mo, Qianxing; Pazhanisamy, Senthil; Krasnow, Ross; Lerner, Seth P.; Chen, Fengju; Roh, Terrence T.; Lay, Erica; Ho, Philip Levy; Chan, Keith Syson

    2015-01-01

    Cytotoxic chemotherapy is effective in debulking tumour masses initially; however, in some patients tumours become progressively unresponsive after multiple treatment cycles. Previous studies have demonstrated that cancer stem cells (CSCs) are selectively enriched after chemotherapy through enhanced survival1–3. Here we reveal a new mechanism by which bladder CSCs actively contribute to therapeutic resistance via an unexpected proliferative response to re-populate residual tumours between chemotherapy cycles, using human bladder cancer xenografts. Further analyses demonstrate the recruitment of a quiescent label-retaining pool of CSCs into cell division in response to chemotherapy-induced damages, similar to mobilization of normal stem cells during wound repair4–7. While chemotherapy effectively induces apoptosis, associated prostaglandin E2 (PGE2) release paradoxically promotes neighbouring CSC repopulation. This repopulation can be abrogated by a PGE2-neutralizing antibody and celecoxib drug-mediated blockade of PGE2 signalling. In vivo administration of the cyclooxygenase-2 (COX2) inhibitor celecoxib effectively abolishes a PGE2- and COX2-mediated wound response gene signature, and attenuates progressive manifestation of chemoresistance in xenograft tumours, including primary xenografts derived from a patient who was resistant to chemotherapy. Collectively, these findings uncover a new underlying mechanism that models the progressive development of clinical chemoresistance, and implicate an adjunctive therapy to enhance chemotherapeutic response of bladder urothelial carcinomas by abrogating early tumour repopulation. PMID:25470039

  7. Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance.

    PubMed

    Kurtova, Antonina V; Xiao, Jing; Mo, Qianxing; Pazhanisamy, Senthil; Krasnow, Ross; Lerner, Seth P; Chen, Fengju; Roh, Terrence T; Lay, Erica; Ho, Philip Levy; Chan, Keith Syson

    2015-01-08

    Cytotoxic chemotherapy is effective in debulking tumour masses initially; however, in some patients tumours become progressively unresponsive after multiple treatment cycles. Previous studies have demonstrated that cancer stem cells (CSCs) are selectively enriched after chemotherapy through enhanced survival. Here we reveal a new mechanism by which bladder CSCs actively contribute to therapeutic resistance via an unexpected proliferative response to repopulate residual tumours between chemotherapy cycles, using human bladder cancer xenografts. Further analyses demonstrate the recruitment of a quiescent label-retaining pool of CSCs into cell division in response to chemotherapy-induced damages, similar to mobilization of normal stem cells during wound repair. While chemotherapy effectively induces apoptosis, associated prostaglandin E2 (PGE2) release paradoxically promotes neighbouring CSC repopulation. This repopulation can be abrogated by a PGE2-neutralizing antibody and celecoxib drug-mediated blockade of PGE2 signalling. In vivo administration of the cyclooxygenase-2 (COX2) inhibitor celecoxib effectively abolishes a PGE2- and COX2-mediated wound response gene signature, and attenuates progressive manifestation of chemoresistance in xenograft tumours, including primary xenografts derived from a patient who was resistant to chemotherapy. Collectively, these findings uncover a new underlying mechanism that models the progressive development of clinical chemoresistance, and implicate an adjunctive therapy to enhance chemotherapeutic response of bladder urothelial carcinomas by abrogating early tumour repopulation.

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

    PubMed

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

    2014-01-01

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

  9. Amygdalin Influences Bladder Cancer Cell Adhesion and Invasion In Vitro

    PubMed Central

    Makarević, Jasmina; Rutz, Jochen; Juengel, Eva; Kaulfuss, Silke; Tsaur, Igor; Nelson, Karen; Pfitzenmaier, Jesco

    2014-01-01

    The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml) was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as well as tumor cell migration was examined. Effects of drug treatment on integrin α and β subtypes, on integrin-linked kinase (ILK) and total and activated focal adhesion kinase (FAK) were also determined. Integrin knock-down was carried out to evaluate integrin influence on migration and adhesion. A 24 h or 2 week amygdalin application distinctly reduced tumor cell adhesion and migration of UMUC-3 and RT112 cells. TCCSUP adhesion was also reduced, but migration was elevated under amygdalin. Integrin subtype expression was significantly and specifically altered by amygdalin depending on the cell line. ILK was moderately, and activated FAK strongly, lost in all tumor cell lines in the presence of amygdalin. Knock down of β1 integrin caused a significant decrease in both adhesion and migration of UMUC-3 cells, but a significant increase in TCCSUP adhesion. Knock down of β4 integrin caused a significant decrease in migration of RT112 cells. Since the different actions of amygdalin on the different cell lines was mirrored by β1 or β4 knock down, it is postulated that amygdalin influences adhesion and migratory properties of bladder cancer cells by modulating β1 or β4 integrin expression. The amygdalin induced increase in TCCSUP migratory behavior indicates that any anti-tumor benefits from amygdalin (seen with the other two cell lines) may depend upon the cancer cell type. PMID:25333694

  10. 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.

  11. ADVANCES IN IMAGING TECHNOLOGIES IN THE EVALUATION OF HIGH-GRADE BLADDER CANCER

    PubMed Central

    Zlatev, Dimitar V.; Altobelli, Emanuela; Liao, Joseph C.

    2015-01-01

    Bladder cancer is a heterogeneous disease that ranges from low-grade variant with an indolent course, to high-grade subtype with a recurrent, progressive, and potentially lethal outcome. Accurate assessment for individualized treatment depends critically on the diagnostic accuracy of white light cystoscopy. Despite its central role, white light cystoscopy has several well-documented shortcomings including difficult flat lesion detection, imprecise tumor delineation that limits complete resection, differentiation between inflammation and malignancy, and grade and stage determination. As the limitations of white light cystoscopy contribute to the risk of cancer persistence, recurrence, and progression, there is a need for improved visualization of flat, multifocal, high-grade, and muscle-invasive lesions. Optical imaging technologies have emerged as an adjunct to white light cystoscopy with the goal to guide more effective treatment by improving cancer detection and patient stratification on the basis of grade and stage. Photodynamic diagnosis and narrow band imaging are macroscopic imaging modalities similar to white light cystoscopy, but provide additional contrast enhancement of bladder tumors and have been shown to improve detection rates. Confocal laser endomicroscopy and optical coherence tomography are microscopic imaging technologies that enable real-time high resolution, subsurface tissue characterization with spatial resolutions similar to histology. Molecular imaging offers the potential for the combination of optical imaging technologies with cancer-specific molecular agents to improve the specificity of disease detection. PMID:25882557

  12. Physical activity and risk of prostate and bladder cancer in China: The South and East China case-control study on prostate and bladder cancer

    PubMed Central

    de Vogel, Stefan; Zhong, Weide; Zhong, Zhaohui; Xie, Li-Ping; Hu, Zhiquan; Deng, Yilan; Yang, Kai; Liang, Yuxiang; Zeng, Xing; Wong, Yong Chuan; Tam, Po-Chor; Hemelt, Marjolein; Zeegers, Maurice P.

    2017-01-01

    Background Recent meta-analyses have suggested a modest protective effect of high levels of physical activity on developing both prostate and bladder cancer, but significant heterogeneity between studies included in these meta-analyses existed. To our knowledge, few Chinese studies investigated the association between physical activity and prostate cancer and none between physical activity and bladder cancer. Given the inconsistencies between previous studies and because studies on the relation between physical activity and prostate and bladder cancer in China are scarce, it remains elusive whether there is a relationship between physical activity and prostate and bladder cancer within the Chinese population. Methods We investigated the association between physical activity and risk of developing prostate and bladder cancer within a hospital-based case-control study in the East and South of China among 260 and 438 incident prostate and bladder cancer cases, respectively, and 427 controls. A questionnaire was administered to measure physical activity as metabolic equivalents (METs). Random effects logistic regression was used to calculate odds ratios (ORs) of prostate and bladder cancer for different levels of physical activity and for the specific activities of walking and cycling. Results Increasing overall physical activity was associated with a significant reduction in prostate cancer risk (Ptrend = 0.04) with the highest activity tertile level showing a nearly 50% reduction in prostate cancer risk (OR = 0.53, 95%CI: 0.28–0.98). Overall physical activity was not significantly associated with risk of bladder cancer (Ptrend = 0.61), neither were vigorous (Ptrend = 0.60) or moderate levels of physical activity (Ptrend = 0.21). Walking and cycling were not significantly associated with either prostate (Ptrend> = 0.62) or bladder cancer risk (Ptrend> = 0.25). Conclusions The findings of this largest ever case-control study in China investigating the relationship

  13. Bladder Cancer Incidence and Mortality: A Global Overview and Recent Trends.

    PubMed

    Antoni, Sebastien; Ferlay, Jacques; Soerjomataram, Isabelle; Znaor, Ariana; Jemal, Ahmedin; Bray, Freddie

    2017-01-01

    Bladder cancer has become a common cancer globally, with an estimated 430 000 new cases diagnosed in 2012. We examine the most recent global bladder cancer incidence and mortality patterns and trends, the current understanding of the aetiology of the disease, and specific issues that may influence the registration and reporting of bladder cancer. Global bladder cancer incidence and mortality statistics are based on data from the International Agency for Research on Cancer and the World Health Organisation (Cancer Incidence in Five Continents, GLOBOCAN, and the World Health Organisation Mortality). Bladder cancer ranks as the ninth most frequently-diagnosed cancer worldwide, with the highest incidence rates observed in men in Southern and Western Europe, North America, as well in certain countries in Northern Africa or Western Asia. Incidence rates are consistently lower in women than men, although sex differences varied greatly between countries. Diverging incidence trends were also observed by sex in many countries, with stabilising or declining rates in men but some increasing trends seen for women. Bladder cancer ranks 13th in terms of deaths ranks, with mortality rates decreasing particularly in the most developed countries; the exceptions are countries undergoing rapid economic transition, including in Central and South America, some central, southern, and eastern European countries, and the Baltic countries. The observed patterns and trends of bladder cancer incidence worldwide appear to reflect the prevalence of tobacco smoking, although infection with Schistosoma haematobium and other risk factors are major causes in selected populations. Differences in coding and registration practices need to be considered when comparing bladder cancer statistics geographically or over time. The main risk factor for bladder cancer is tobacco smoking. The observed patterns and trends of bladder cancer incidence worldwide appear to reflect the prevalence of tobacco smoking

  14. Forced diuresis and dual-phase 18F-fluorodeoxyglucose-PET/CT scan for restaging of urinary bladder cancers

    PubMed Central

    Harkirat, S; Anand, SS; Jacob, MJ

    2010-01-01

    Context: The results of 18F-fluorodeoxyglucose (FDG)-PET imaging carried out with the current standard techniques for assessment of urinary tract cancers have been reported to be less than satisfactory because of the urinary excretion of the tracer. Aims: To investigate the role of dual-phase FDG-PET/CT in the restaging of invasive cancers of the urinary bladder, with delayed imaging after forced diuresis and oral hydration as the scanning protocol. Settings and Design: FDG-PET has been considered to be of limited value for the detection of urinary tract cancers because of interference by the FDG excreted in urine. We investigated the efficacy of delayed FDG-PET/CT in the restaging of invasive bladder cancer, with imaging performed after intravenous (IV) administration of a potent diuretic and oral hydration. Materials and Methods: Twenty-nine patients with invasive cancer of the urinary bladder were included in this study. Patients were divided into two groups: Group I (22 patients) included cases with invasive bladder cancer who had not undergone cystectomy and group II (seven patients) included cases with invasive bladder cancer who had undergone cystectomy and urinary diversion procedure. All patients underwent FDG-PET/CT scan from the skull base to the mid-thighs 60 min after IV injection of 370 mega-Becquerel (MBq) of FDG. Additional delayed images were acquired 60-90 min after IV furosemide and oral hydration. PET/CT data were analyzed as PET and CT images studied separately as well as fused PET/CT images and the findings were recorded. The imaging findings were confirmed by cystoscopy, biopsy or follow-up PET/CT. Results: The technique was successful in achieving adequate washout of urinary FDG and overcame the problems posed by the excess FDG in the urinary tract. Hypermetabolic lesions could be easily detected by PET and precisely localized to the bladder wall, perivesical region and pelvic lymph nodes. PET/CT delayed images were able to demonstrate 16

  15. 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.

  16. 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.

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

    PubMed

    Shahait, Mohammed; Bulbul, Muhammad

    2016-10-27

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

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

    PubMed Central

    2014-01-01

    Background Development and further characterization of animal models for human cancers is important for the improvement of cancer detection and therapy. Canine bladder cancer closely resembles human bladder cancer in many aspects. In this study, we isolated and characterized four primary transitional cell carcinoma (K9TCC) cell lines to be used for future in vitro validation of novel therapeutic agents for bladder cancer. Methods Four K9TCC cell lines were established from naturally-occurring canine bladder cancers obtained from four dogs. Cell proliferation rates of K9TCC cells in vitro were characterized by doubling time. The expression profile of cell-cycle proteins, cytokeratin, E-cadherin, COX-2, PDGFR, VEGFR, and EGFR were evaluated by immunocytochemistry (ICC) and Western blotting (WB) analysis and compared with established human bladder TCC cell lines, T24 and UMUC-3. All tested K9TCC cell lines were assessed for tumorigenic behavior using athymic mice in vivo. Results Four established K9TCC cell lines: K9TCC#1Lillie, K9TCC#2Dakota, K9TCC#4Molly, and K9TCC#5Lilly were confirmed to have an epithelial-cell origin by morphology analysis, cytokeratin, and E-cadherin expressions. The tested K9TCC cells expressed UPIa (a specific marker of the urothelial cells), COX-2, PDGFR, and EGFR; however they lacked the expression of VEGFR. All tested K9TCC cell lines confirmed a tumorigenic behavior in athymic mice with 100% tumor incidence. Conclusions The established K9TCC cell lines (K9TCC#1Lillie, K9TCC#2Dakota, K9TCC#4Molly, and K9TCC#5Lilly) can be further utilized to assist in development of new target-specific imaging and therapeutic agents for canine and human bladder cancer. PMID:24964787

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

    PubMed

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

    2007-01-01

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

  20. Immunotherapy Beats Chemo for Bladder Cancer.

    PubMed

    2017-05-01

    Patients with advanced urothelial carcinoma live 3 months longer, on average, when given pembrolizumab as a second-line treatment instead of chemotherapy. The finding is based on data from the first phase III trial to test an immunotherapeutic in these patients, which could lead to another label indication for the PD-1 inhibitor. ©2017 American Association for Cancer Research.

  1. Stat3 Activation in Urothelial Stem Cells Leads to Direct Progression to Invasive Bladder Cancer

    PubMed Central

    Ho, Philip Levy; Lay, Erica Julianne; Jian, Weiguo; Parra, Diana; Chan, Keith Syson

    2012-01-01

    Two subtypes of human bladder cancer, noninvasive papillary and muscle-invasive cancer, develop through independent pathologic and molecular pathways. Human invasive bladder cancer frequently develops without prior clinical evidence of a noninvasive tumor stage. However, an animal model that recapitulates this unique clinical progression of invasive bladder cancer has not yet been developed. In this study, we created a novel transgenic mouse model of invasive bladder cancer by targeting an active dimerized form of Stat3 to the basal cells of bladder epithelium. When exposed to the carcinogen nitrosamine, Stat3-transgenic mice developed invasive cancer directly from carcinoma in situ (CIS), bypassing the noninvasive papillary tumor stage. Remarkably, invasive bladder cancer driven by active Stat3 was predominantly composed of stem cells, which were characterized by cytokeratin 14 (CK14) staining and enhanced tumor sphere-forming ability. Active Stat3 was also shown to localize to the nucleus of human invasive bladder cancers that were primarily composed of CK14+ stem cells. Together, our findings show that Stat3-induced stem cell expansion plays a critical role in the unique clinical progression of invasive bladder cancer through the CIS pathway. PMID:22532166

  2. Expression of Aggrus/podoplanin in bladder cancer and its role in pulmonary metastasis

    PubMed Central

    Takagi, Satoshi; Oh-hara, Tomoko; Sato, Shigeo; Gong, Bo; Takami, Miho; Fujita, Naoya

    2014-01-01

    Platelet aggregation-inducing factor Aggrus, also known as podoplanin, is associated with tumor malignancy by promoting hematogenous metastasis. Aggrus overexpression has been reported in some tumor tissues including lung, esophagus, head and neck and brain. We here found the frequent upregulation of aggrus mRNA in urinary bladder cancers using cancer tissue panels from various organs. Immunohistochemical analysis confirmed Aggrus protein expression in urinary bladder cancers and suggested a positive correlation between Aggrus expression and metastatic tendency in bladder cancers. Endogenous expression of Aggrus protein on the cell surface was found in the mouse bladder cancer MBT-2 cell line and human bladder cancer SCaBER cell lines. Knockdown of Aggrus expression in MBT-2 cells decreased their ability to induce platelet aggregation and form pulmonary metastasis in syngeneic mouse models. Knockdown of Aggrus expression in the human bladder cancer SCaBER cells also attenuated their ability to induce platelet aggregation and form pulmonary metastasis in mice. Moreover, pulmonary metastasis of SCaBER cells was prevented by prior administration of our generated anti-Aggrus neutralizing monoclonal antibodies by attenuating their retention in lung. These results indicate that Aggrus plays an important role in bladder cancer metastasis. Thus, anti-Aggrus neutralizing antibodies would be useful for the prevention of hematogenous metastasis of Aggrus-positive bladder cancer. PMID:24222607

  3. RNAi-based therapeutics targeting survivin and PLK1 for treatment of bladder cancer.

    PubMed

    Seth, Shaguna; Matsui, Yoshiyuki; Fosnaugh, Kathy; Liu, Yan; Vaish, Narendra; Adami, Roger; Harvie, Pierrot; Johns, Rachel; Severson, Gregory; Brown, Tod; Takagi, Akihide; Bell, Susan; Chen, Yan; Chen, Feng; Zhu, Tianying; Fam, Renata; Maciagiewicz, Iwona; Kwang, Erin; McCutcheon, Michael; Farber, Ken; Charmley, Patrick; Houston, Michael E; So, Alan; Templin, Michael V; Polisky, Barry

    2011-05-01

    Harnessing RNA interference (RNAi) to silence aberrant gene expression is an emerging approach in cancer therapy. Selective inhibition of an overexpressed gene via RNAi requires a highly efficacious, target-specific short interfering RNA (siRNA) and a safe and efficient delivery system. We have developed siRNA constructs (UsiRNA) that contain unlocked nucleobase analogs (UNA) targeting survivin and polo-like kinase-1 (PLK1) genes. UsiRNAs were encapsulated into dialkylated amino acid-based liposomes (DiLA(2)) containing a nor-arginine head group, cholesteryl hemisuccinate (CHEMS), cholesterol and 1, 2-dimyristoyl-phosphatidylethanolamine-polyethyleneglycol 2000 (DMPE-PEG2000). In an orthotopic bladder cancer mouse model, intravesical treatment with survivin or PLK1 UsiRNA in DiLA(2) liposomes at 1.0 and 0.5 mg/kg resulted in 90% and 70% inhibition of survivin or PLK1 mRNA, respectively. This correlated with a dose-dependent decrease in tumor volumes which was sustained over a 3-week period. Silencing of survivin and PLK1 mRNA was confirmed to be RNA-induced silencing complex mediated as specific cleavage products were detected in bladder tumors over the duration of the study. This report suggests that intravesical instillation of survivin or PLK1 UsiRNA can serve as a potential therapeutic modality for treatment of bladder cancer.

  4. Possible relation between the NOS3 gene GLU298ASP polymorphism and bladder cancer in Turkey.

    PubMed

    Verim, Levent; Toptas, Bahar; Ozkan, Nazli Ezgi; Cacina, Canan; Turan, Saime; Korkmaz, Gurbet; Yaylim, Ilhan

    2013-01-01

    Endothelial nitric oxide synthase (eNOS), encoded by the NOS3 gene, has been suggested to play an important role in uncontrolled cell growth in several cancer types. The objective of this study was to evaluate the role of the NOS3 Glu298Asp polymorphism in bladder cancer susceptibility in a Turkish population. We determined the genotypes of 66 bladder cancer cases and 88 healthy controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. A significant association for NOS3 Glu298Asp heterozygotes genotypes and T allely were found between healthy controls and bladder cancer, respectively (p<0.001: p=0.002). There were no significant associations between any genotypes and the stage, grade, and histological type of bladder cancer. Our study suggested an increased risk role of NOS3 GT genotype in bladder cancer susceptibility in our Turkish population.

  5. Value of urinary topoisomerase-IIA cell-free DNA for diagnosis of bladder cancer.

    PubMed

    Kim, Ye-Hwan; Yan, Chunri; Lee, Il-Seok; Piao, Xuan-Mei; Byun, Young Joon; Jeong, Pildu; Kim, Won Tae; Yun, Seok-Joong; Kim, Wun-Jae

    2016-03-01

    Topoisomerase-II alpha (TopoIIA ), a DNA gyrase isoform that plays an important role in the cell cycle, is present in normal tissues and various human cancers, and can show altered expression in both. The aim of the current study was to examine the value of urinary TopoIIA cell-free DNA as a noninvasive diagnosis of bladder cancer (BC). Two patient cohorts were examined. Cohort 1 (73 BC patients and seven controls) provided bladder tissue samples, whereas cohort 2 (83 BC patients, 54 nonmalignant hematuric patients, and 61 normal controls) provided urine samples. Real-time quantitative polymerase chain reaction was used to measure expression of TopoIIA mRNA in tissues and TopoIIA cell-free DNA in urine samples. The results showed that expression of TopoIIA mRNA in BC tissues was significantly higher than that in noncancer control tissues (p<0.001). The expression of urinary TopoIIA cell-free DNA in BC patients was also significantly higher than that in noncancer patient controls and hematuria patients (p < 0.001 and p < 0.001, respectively). High expression of urinary TopoIIA cell-free DNA was also detected in muscle invasive bladder cancer (MIBC) when compared with nonmuscle invasive bladder cancer (NMIBC) (p=0.002). Receiver operating characteristics (ROC) curve analysis was performed to examine the sensitivity/specificity of urinary TopoIIA cell-free DNA for diagnosing BC, NMIBC, and MIBC. The areas under the ROC curve for BC, NMIBC, and MIBC were 0.741, 0.701, and 0.838, respectively. In summary, the results of this study provide evidence that cell-free TopoIIA DNA may be a potential biomarker for BC.

  6. Peritoneal bladder fistula following radiotherapy for cervical cancer: A case report

    PubMed Central

    Shi, Fan; Wang, Tao; Wang, Jiquan; Hui, Beina; Chai, Yanlan; Wang, Juan; Liu, Zi

    2016-01-01

    The occurrence of a peritoneal bladder fistula as a result of radiation cystitis following radiotherapy for cervical cancer is extremely rare and, to the best of our knowledge, has not been reported previously. The present study reports the case of a 50-year-old woman who was diagnosed with cervical cancer 20 years previously and was treated with radiotherapy. The patient was diagnosed with radiation cystitis 10 years ago, which was treated with Chinese medicine, and began experiencing sudden abdominal pain and bowel difficulties following urination 3 years ago. B-ultrasound examination at The People's Hospital of Tongchuan (Tongchuan, China) detected the presence of abdominal pelvic fluid. Following antibiotic (levofloxacin for 5 days) and ascites extraction treatment, symptoms were relieved without recurrence. However, 5 days prior to admission to the First Affiliated Hospital of Xi'an Jiatong University (Xi'an, China) on June 25, 2014, the patient experienced difficulty when urinating, abdominal pain and bloating, but did not experience frequent urination, hematuria or fever. Cystoscopic examination revealed a visible fistula on the bladder wall measuring 1×1 cm in diameter. Cytoscopic examination 1 month after catheterization and ascites extraction revealed no evidence of the fistula. The patient was followed up every 3 months for a year and a half, and is currently alive and well. In conclusion, the occurrence of peritoneal bladder fistula following radiation therapy is rare and cystoscopy is the preferred method of examination and diagnosis. Early detection and treatment may significantly improve the prognosis of patients. PMID:27602129

  7. Elevated 4-Aminobiphenyl and 2, 6-Dimethylaniline Hemoglobin Adducts and Increased Risk of Bladder Cancer among Lifelong Nonsmokers - The Shanghai Bladder Cancer Study

    PubMed Central

    Tao, Li; Day, Billy W.; Hu, Bibin; Xiang, Yong-Bing; Wang, Renwei; Stern, Mariana C.; Gago-Dominguez, Manuela; Cortessis, Victoria K.; Conti, David V.; Van Den Berg, David; Pike, Malcolm C.; Gao, Yu-Tang; Yu, Mimi C.; Yuan, Jian-Min

    2014-01-01

    Background 4-Aminobiphenyl (ABP) is an established human bladder carcinogen, with tobacco smoke being a major source of human exposure. Other arylamine compounds, including 2,6-dimethylaniline (2,6-DMA), have been implicated as possible human bladder carcinogens. Hemoglobin adducts of 4-ABP and 2,6-DMA are validated biomarkers of exposure to those compounds in humans. Methods The Shanghai Bladder Cancer Study enrolled 581 incident bladder cancer cases and 604 population controls. Each participant was solicited for his/her history of tobacco use and other lifestyle factors, and donation of blood and urine specimens. Red blood cell lysates were used to quantify both hemoglobin adducts of 4-ABP and 2,6-DMA. Urine samples were used to quantify total cotinine. Odds ratios (ORs) and 95% confidence intervals (CIs) for bladder cancer were estimated using unconditional logistic regression methods. Results Among lifelong nonsmokers, ORs (95% CIs) of bladder cancer for low (below median of positive values) and high versus undetectable levels of 2,6-DMA hemoglobin adducts were 3.87 (1.39-10.75) and 6.90 (3.17-15.02), respectively (Ptrend<0.001). Similarly, among lifelong nonsmokers, ORs (95% CIs) of bladder cancer for 3rd and 4th versus 1st/2nd quartiles of 4-ABP hemoglobin adducts was 1.30 (0.76-2.22) and 2.29 (1.23-4.24), respectively (Ptrend=0.00). The two associations were independent of each other. Conclusion Hemoglobin adducts of 4-ABP and 2,6-DMA were significantly and independently associated with increased bladder cancer risk among lifelong nonsmokers in Shanghai, China. Impact The findings of the present study in China with previous data in Los Angeles, California strongly implicate arylamines as potential causal agents of human bladder cancer. PMID:23539508

  8. Agricultural exposure and risk of bladder cancer in the AGRIculture and CANcer cohort.

    PubMed

    Boulanger, Mathilde; Tual, Séverine; Lemarchand, Clémentine; Guizard, Anne-Valérie; Velten, Michel; Marcotullio, Elisabeth; Baldi, Isabelle; Clin, Bénédicte; Lebailly, Pierre

    2017-02-01

    Literature on agricultural activities and bladder cancer risk is scarce. However, farmers can be subjected to carcinogenic exposure (e.g. arsenic, previously used as a pesticide in France). This study aimed at assessing the role of a large range of agricultural activities and tasks on bladder cancer risk. The study population was the AGRIculture and CANcer cohort, a large prospective cohort of individuals affiliated to the agricultural health insurance scheme (MSA) in France. Incident bladder cancers were identified by cancer registries from enrolment (2005-2007) to 2009. Data on agricultural exposure during professional lifetime (5 animals, 13 crops, specific tasks) were obtained from the enrolment questionnaire. Associations between bladder cancer and agricultural exposure were analysed using a Cox model, adjusted for gender and smoking history. Among the 148,051 farm owners and workers included in this analysis, 179 incident bladder cancers were identified. We observed an elevated risk among field-grown vegetable workers [HR 1.89, 95% CI (1.20-2.99)], with an exposure-response relationship with duration of work [≥30 years: HR 2.54, 95% CI (1.11-5.83), p-trend = 0.02], and higher risk among women [HR 3.82, 95% CI (1.58-9.25), p-interaction = 0.05]. Non-significantly increased risks were also observed in greenhouse farmers (HR = 1.95), pea sowing (HR = 1.84), rape sowing (HR = 1.64); several tasks involving pesticide use, especially seed treatment (HR = 1.24); and in activities and tasks potentially exposing to arsenic compounds via pesticide use (HR = 1.49) or re-entry tasks (HR = 1.63). Our analyses raise the question of a possible link between agricultural activity, especially field-grown vegetables, and greenhouse cultivation and bladder cancer.

  9. MUC1 mucin as a tumour marker in bladder cancer.

    PubMed

    Simms, M S; Hughes, O D; Limb, M; Price, M R; Bishop, M C

    1999-08-01

    To evaluate serum MUC1 levels (a high molecular weight glycoprotein which is upregulated and abnormally glycosylated in bladder cancer and other carcinomas) in patients with a variety of stages and grades of transitional cell carcinoma (TCC) of the bladder, to assess its potential as a tumour marker. Blood samples were taken before treatment in 87 patients with TCC of the bladder and in 31 controls undergoing cystoscopy for benign conditions. Serum MUC1 levels were estimated with an enzyme-linked immunosorbent assay using the C595 monoclonal antibody. Of patients with T4 tumours, 47% had MUC1 levels above the normal range (P<0.001); patients with T3 tumours also had significantly higher MUC1 levels than controls. The overall sensitivity was only 24% for all tumours when the upper limit of normal was defined as 4.8 U/mL; the specificity was 97%. Serum MUC1 is not as useful tumour marker for screening, as it has a low sensitivity. However, MUC1 levels are high in advanced disease and serum MUC1 levels may be useful for disease monitoring.

  10. 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...

  11. MiR-122 targets VEGFC in bladder cancer to inhibit tumor growth and angiogenesis

    PubMed Central

    Wang, Yi; Xing, Qing-Fei; Liu, Xiao-Qiang; Guo, Zhan-Jun; Li, Chang-Ying; Sun, Guang

    2016-01-01

    Previous studies indicate that microRNA-122 (miR-122) is down-regulated in several cancer cells and regulates cell apoptosis, proliferation, metastasis, and tumor angiogenesis. However, the mount of miR-122 in bladder cancer and the pivotal molecular mechanisms of miR-122 used to regulate bladder carcinogenesis and angiogenesis remain to be clarified. Here, we reveal that miR-122 expression is down-regulated in human bladder cancer tissues and cell lines. MiR-122 represses vascular endothelial growth factor C (VEGFC) post-transcriptional expression by directly binding to its 3’-UTR. The protein kinase B (AKT) and mammalian target of rapamycin (mTOR), which are the most important downstream molecules of VEGFC, are also decreased in bladder cancer cell after miR-122 overexpression. Furthermore, miR-122 over-expression decreases bladder cancer cell migration, invasion, colony formation in vitro and slow bladder cancer growth and angiogenesis in vivo. Finally, miR-122 sensitizes bladder cancer cells to cisplatin-induced apoptosis. Taken together, these studies suggest that miR-122 serves as a tumor suppressor and down-regulating VEGFC expression, leading to the inhibition of bladder cancer growth and angiogenesis. PMID:27508026

  12. Long noncoding RNA linc00346 promotes the malignant phenotypes of bladder cancer.

    PubMed

    Ye, Tingyu; Ding, Wei; Wang, Nanxiong; Huang, Hang; Pan, Yue; Wei, Anyang

    2017-09-09

    More and more reports have demonstrated that long noncoding RNAs (lncRNAs) play an important role in the development of a variety of carcinomas, including bladder cancer. However, only a small fraction of them have been characterized. Linc00346 have been found to be upregulated in bladder cancer tissues compared to normal tissues in a microarray-based lncRNA profiling study. In this study, we would like to explore the expression pattern and functional role of linc00346 in bladder cancer. We determined the expression of linc00346 in a cohort of bladder cancer tissues with matched normal tissues as well as human bladder cancer cell lines. We investigated the biological function of linc00346 with CCK-8 assay, colony formation assay, flow cytometry analysis, transwell assay and tumor xenografts mice model. We found that linc00346 was upregulated in bladder cancer tissues compared to normal tissues. Knockdown of linc00346 inhibited bladder cancer cell proliferation and migration, induced cell cycle arrest and cell apoptosis. Our study demonstrates that linc00346 could be a potential oncogene and a therapeutic target in bladder cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2015-11-10

    A tumor microenvironment may promote tumor metastasis and progression through the dynamic interplay between neoplastic cells and stromal cells. In this work, the most representative and significant stromal cells, fibroblasts, endothelial cells, and macrophages were used as vital component elements and combined with bladder cancer cells to construct a bladder cancer microenvironment simulation system. This is the first report to explore bladder cancer microenvironments based on 4 types of cells co-cultured simultaneously. This simulation system comprises perfusion equipment, matrigel channel units, a medium channel and four indirect contact culture chambers, allowing four types of cells to simultaneously interact through soluble biological factors and metabolites. With this system, bladder cancer cells (T24) with a tendency to form a 'reticular' structure under 3 dimensional culture conditions were observed in real time. The microenvironment characteristics of paracrine interactions and cell motility were successfully simulated in this system. The phenotype change process in stromal cells was successfully reproduced in this system by testing the macrophage effector molecule Arg-1. Arg-1 was highly expressed in the simulated tumor microenvironment group. To develop "precision medicine" in bladder cancer therapy, bladder cancer cells were treated with different clinical 'neo-adjuvant' chemotherapy schemes in this system, and their sensitivity differences were fully reflected. This work provides a preliminary foundation for neo-adjuvant chemotherapy in bladder cancer, a theoretical foundation for tumor microenvironment simulation and promotes individual therapy in bladder cancer patients.

  14. 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...

  15. The role of the androgen receptor in the development and progression of bladder cancer.

    PubMed

    Li, Yi; Izumi, Koji; Miyamoto, Hiroshi

    2012-07-01

    Men are at a higher risk of developing bladder cancer than women. Since bladder cancer cell lines and tissues were found to express the androgen receptor, efforts have been made to inspect whether androgen-mediated androgen receptor signals are implicated in bladder carcinogenesis as well as cancer progression. Mounting evidence supports the view that bladder cancer is a member of the endocrine-related tumors and may clearly explain the gender-specific difference in the incidence. However, the underlying mechanisms of how androgen receptor signals regulate bladder