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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. Bladder Cancer

    MedlinePlus

    ... organ in your lower abdomen that stores urine. Bladder cancer occurs in the lining of the bladder. It ... urinate Low back pain Risk factors for developing bladder cancer include smoking and exposure to certain chemicals in ...

  3. 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

  4. Bladder cancer

    MedlinePlus

    ... removing the rest of the bladder Chemotherapy or immunotherapy placed directly into the bladder Stage II and ... IV), chemotherapy is usually given by vein (intravenously). IMMUNOTHERAPY Bladder cancers are often treated with immunotherapy. In ...

  5. Detecting recurrent bladder cancer: new methods and biomarkers.

    PubMed

    Ross, J S; Cohen, M B

    2001-05-01

    In this review, a series of biomarkers and molecular assays are compared with conventional urothelial cytology in their ability to detect recurrent bladder cancer. The tests considered in detail include the BTA test, NMP 22 test, DNA ploidy measurements, telomerase determinations and microsatellite instability assays. Although all of these measurements show some degree of improvement for cancer detection, the microsatellite instability assay shows the highest sensitivity and specificity. Additional biomarkers considered in the review include bladder cancer tumor antigens, growth factors, cell adhesion molecules and various molecular markers including cell cycle regulatory genes and p53 mutations.

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

    PubMed Central

    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, KK; Mathews, Glenn M.; Patel, Prashant; Griffiths, Michael; Bryan, Richard T.

    2016-01-01

    Background 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. Methods 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). Results 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). Conclusion 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. PMID:26901314

  7. Biomarkers for the detection of bladder cancer.

    PubMed

    Ross, J S; Cohen, M B

    2001-01-01

    In this subject review, a series of morphology-based and molecular markers were compared with urinary cytology for the detection of recurrent urothelial neoplasia. Among the various biomarkers reviewed, the average published sensitivity and specificity for the Bard BTA test was 60% and 77%; the NMP22 Test was 67% and 72%; the telomerase assay was 77% and 85%; and the microsatellite assay was 89% and 100%. DNA ploidy measurements and immunoassays designed to detect keratins, proteins, hyaluronidase, growth factors, cell adhesion molecules, fibrinogen degradation products, cell cycle regulators, and molecular markers were also included. Although the performance features of these biomarkers have varied and the cytologic methods to which they have been compared have not been standardized, several of the procedures have received considerable support from urologists as assisting them in the management of their patients.

  8. 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

  9. Bladder Cancer Advocacy Network

    MedlinePlus

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

  10. 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

  11. Drugs Approved for Bladder Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Bladder Cancer This page lists cancer ... in bladder cancer that are not listed here. Drugs Approved for Bladder Cancer Atezolizumab Cisplatin Doxorubicin Hydrochloride ...

  12. Incidental Bladder Cancer Detected on Multiparametric Magnetic Resonance Imaging of the Prostate Gland

    PubMed Central

    Sardari, Al; Thomas, John V.; Nix, Jeffrey W.; Pietryga, Jason A.; Sanyal, Rupan; Gordetsky, Jennifer B.; Rais-Bahrami, Soroush

    2015-01-01

    The increased use of axial imaging in various fields of medicine has led to an increased frequency of incidental findings, specifically incidental cancer lesions. Hence, as the use of multiparametric magnetic resonance imaging (MP-MRI) for prostate cancer detection, staging, and management becomes more widespread, the potential for additional incidental findings in the pelvis increases. Herein, we report the case of a man on active surveillance for low-grade, early-staged prostate cancer who underwent MP-MRI and was incidentally found to have a high-grade bladder cancer lesion. PMID:26783492

  13. 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.

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

    PubMed

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

    2010-01-01

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

  15. 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. PMID:26087450

  16. 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.

  17. 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

  18. General Information about Bladder Cancer

    MedlinePlus

    ... Research Bladder Cancer Treatment (PDQ®)–Patient Version General Information About Bladder Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  19. Use of urine-based markers for detection and monitoring of bladder cancer.

    PubMed

    Pirtskalaishvili, G; Getzenberg, R H; Konety, B R

    1999-12-01

    Diagnosis and monitoring of bladder cancer present a difficult clinical problem. Urine cytology with confirmatory cystoscopy form the cornerstone of diagnosis at the present time. The subjectivity and low sensitivity of cytology led to the development of numerous tests as adjuncts to cystoscopy for the diagnosis and follow-up of bladder cancer patients. These tests usually are objective, quantitative (NMP-22, BTA TRAK, BLCA-4, telomerase activity, etc.), or qualitative (BTA Stat and FDP) and have higher sensitivity than cytology, but some have lower specificity. We review the different, new urine-based tests that were developed recently for the diagnosis and monitoring of patients with bladder cancer. The advantages and disadvantages of these tests are discussed, as well as their possible future role in the management of patients with bladder cancer.

  20. 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.

  1. Pachydermoperiostosis and bladder cancer.

    PubMed

    Famularo, Guiseppe; Stasolla, Alessandro; Gasbarrone, Laura

    2015-06-01

    Pachydermoperiostosis or the Touraine-Soulente-Golé syndrome is a rare monogenetic disorder characterized by pachydermia, periostosis and digital clubbing accounts for approximately 3∼5% of all patients with hypertrophic osteoarthropathy. Missense mutations in SLCO2A1 and HPGD genes could plausibly underlie the pathogenesis of pachydermoperiostosis. Patients have usually a favorable outcome with very few cases associated with cancer. Herein, we report the first case of a patient with pachydermoperiostosis associated with bladder cancer. PMID:26158372

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

    PubMed Central

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

    2013-01-01

    The relationship between inflammation and cancer is well established in several tumor types, including bladder cancer. We performed an association study between 886 inflammatory-gene variants and bladder cancer risk in 1,047 cases and 988 controls from the Spanish Bladder Cancer (SBC)/EPICURO Study. A preliminary exploration with the widely used univariate logistic regression approach did not identify any significant SNP after correcting for multiple testing. We further applied two more comprehensive methods to capture the complexity of bladder cancer genetic susceptibility: Bayesian Threshold LASSO (BTL), a regularized regression method, and AUC-Random Forest, a machine-learning algorithm. Both approaches explore the joint effect of markers. BTL analysis identified a signature of 37 SNPs in 34 genes showing an association with bladder cancer. AUC-RF detected an optimal predictive subset of 56 SNPs. 13 SNPs were identified by both methods in the total population. Using resources from the Texas Bladder Cancer study we were able to replicate 30% of the SNPs assessed. The associations between inflammatory SNPs and bladder cancer were reexamined among non-smokers to eliminate the effect of tobacco, one of the strongest and most prevalent environmental risk factor for this tumor. A 9 SNP-signature was detected by BTL. Here we report, for the first time, a set of SNP in inflammatory genes jointly associated with bladder cancer risk. These results highlight the importance of the complex structure of genetic susceptibility associated with cancer risk. PMID:24391818

  3. Radiochemotherapy for bladder cancer.

    PubMed

    Ott, O J; Rödel, C; Weiss, C; Wittlinger, M; St Krause, F; Dunst, J; Fietkau, R; Sauer, R

    2009-09-01

    Standard treatment for muscle-invasive bladder cancer is cystectomy. Multimodality treatment, including transurethral resection of the bladder tumour, radiation therapy, chemotherapy and deep regional hyperthermia, has been shown to produce survival rates comparable with those of cystectomy. With these programmes, cystectomy has been reserved for patients with incomplete response or local relapse. During the past two decades, organ preservation by multimodality treatment has been investigated in prospective series from single centres and co-operative groups, with more than 1000 patients included. Five-year overall survival rates in the range of 50-60% have been reported, and about three-quarters of the surviving patients maintained their bladder. Clinical criteria helpful in determining patients for bladder preservation include such variables as small tumour size (<5 cm), early tumour stage, a visibly and microscopically complete transurethral resection, absence of ureteral obstruction, and no evidence of pelvic lymph node metastases. On multivariate analysis, the completeness of transurethral resection of a bladder tumour was found to be one of the strongest prognostic factors for overall survival. Patients at greater risk of new tumour development after initial complete response are those with multifocal disease and extensive associated carcinoma in situ at presentation. Close co-ordination among all disciplines is required to achieve optimal results. Future investigations will focus on optimising radiation techniques, including all possibilities of radiosensitisation (e.g. concurrent radiochemotherapy, deep regional hyperthermia), and incorporating more effective systemic chemotherapy, and the proper selection of patients based on predictive molecular makers.

  4. Pharmacogenomics in bladder cancer

    PubMed Central

    Dancik, Garrett M.; Theodorescu, Dan

    2014-01-01

    Bladder cancer is a common cancer worldwide. For patients presenting with muscle-invasive disease, the five year survival rate is approximately 50%. Cisplatinum-based combination chemotherapy is recommended in the neoadjuvant setting prior to cystectomy and is also the first line in the metastatic setting. However, the survival benefit of such therapy is modest. The identification of pharmacogenomic biomarkers would enable the rational and personalized treatment of patients by selecting those patients that would benefit most from such therapies sparing others the unnecessary toxicity. Conventional therapies would be recommended for an expected responder while a non-responder would be considered for alternative therapies selected on the basis of the individual’s molecular profile. Although few effective bladder cancer therapies have been introduced in the past 30 years, several targeted therapies against the molecular drivers of bladder cancer appear promising. This review summarizes pharmacogenomic biomarkers that require further investigation and/or prospective evaluation, publicly available tools for drug discovery and biomarker identification from in vitro data, and targeted agents that have been evaluated in preclinical models. PMID:24360659

  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

    2015-02-01

    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. PMID:25427191

  7. Bladder Cancer and Genetic Mutations.

    PubMed

    Zhang, Xiaoying; Zhang, Yangde

    2015-09-01

    The most common type of urinary bladder cancer is called as transitional cell carcinoma. The major risk factors for bladder cancer are environmental, tobacco smoking, exposure to toxic industrial chemicals and gases, bladder inflammation due to microbial and parasitic infections, as well as some adverse side-effects of medications. The genetic mutations in some chromosomal genes, such as FGFR3, RB1, HRAS, TP53, TSC1, and others, occur which form tumors in the urinary bladder. These genes play an important role in the regulation of cell division which prevents cells from dividing too quickly. The changes in the genes of human chromosome 9 are usually responsible for tumor in bladder cancer, but the genetic mutation of chromosome 22 can also result in bladder cancer. The identification of p53 gene mutation has been studied at NIH, Washington, DC, USA, in urine samples of bladder cancer patients. The invasive bladder cancers were determined for the presence of gene mutations on p53 suppressor gene. The 18 different bladder tumors were evaluated, and 11 (61 %) had genetic mutations of p53 gene. The bladder cancer studies have suggested that 70 % of bladder cancers involve a specific mutation in a particular gene, namely telomerase reverse transcriptase (TERT) gene. The TERT gene is involved in DNA protection, cellular aging processes, and cancer. The Urothelial carcinomas of the bladder have been described in Atlas of genetics and cytogenetics in oncology and hematology. HRAS is a proto-oncogene and has potential to cause cancer in several organs including the bladder. The TSC1 c. 1907 1908 del (E636fs) mutation in bladder cancer suggests that the location of the mutation is Exon 15 with frequency of TSC1 mutation of 11.7 %. The recent findings of BAP1 mutations have shown that it contributes to BRCA pathway alterations in bladder cancer. The discoveries of more gene mutations and new biomarkers and polymerase chain reaction bioassays for gene mutations in bladder

  8. 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

  9. 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

  10. Direct detection of hyaluronidase in urine using cationic gold nanoparticles: a potential diagnostic test for bladder cancer.

    PubMed

    Nossier, Ahmed Ibrahim; Eissa, Sanaa; Ismail, Manal Fouad; Hamdy, Mohamed Ahmed; Azzazy, Hassan Mohamed El-Said

    2014-04-15

    Hyaluronidase (HAase) was reported as a urinary marker of bladder cancer. In this study, a simple colorimetric gold nanoparticle (AuNP) assay was developed for rapid and sensitive detection of urinary HAase activity. Charge interaction between polyanionic hyaluronic acid (HA) and cationic AuNPs stabilized with cetyl trimethyl ammonium bromide (CTAB) led to formation of gold aggregates and a red to blue color shift. HAase digests HA into small fragments preventing the aggregation of cationic AuNPs. The nonspecific aggregation of AuNPs in urine samples was overcome by pre-treatment of samples with the polycationic chitosan that was able to agglomerate all negatively charged interfering moieties before performing the assay. The developed AuNP assay was compared with zymography for qualitative detection of urinary HAase activity in 40 bladder carcinoma patients, 11 benign bladder lesions patients and 15 normal individuals, the assay sensitivity was 82.5% vs. 65% for zymography, while the specificity for both assays was 96.1%. The absorption ratio, A530/A620 of the reacted AuNP solution was used to quantify the HAase activity. The best cut off value was 93.5 μU/ng protein, at which the sensitivity was 90% and the specificity was 80.8%.The developed colorimetric AuNP HAase assay is simple, inexpensive, and can aid noninvasive diagnosis of bladder cancer. PMID:24240162

  11. Emerging Immunotargets in Bladder Cancer.

    PubMed

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

    2016-01-01

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

  12. 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.

  13. Genetics Home Reference: bladder cancer

    MedlinePlus

    ... chemicals. Studies suggest that chronic bladder inflammation, a parasitic infection called schistosomiasis, and some medications used to treat ... Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Patient Support and Advocacy Resources (2 links) American Cancer ...

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

    PubMed

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

    2014-01-01

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

  15. 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

  16. 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.

  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. Cancer of the Urinary Bladder

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 76,960 % of All New Cancer Cases 4.6% Estimated Deaths in 2016 16,390 % of All Cancer ... of This Cancer : In 2013, there were an estimated 587,426 people living with bladder cancer in ...

  19. Ct2 Bladder Cancer.

    PubMed

    Soloway, Mark S

    2016-09-01

    The patient is an 80-year-old man who presented with gross hematuria. His past medical history indicates he was a cigarette smoker with 50 pack/years. He was successfully treated for carcinoma of the lung 7 years ago. He received chemotherapy, radiation, and surgery. He has mild COPD but has a good performance status. His laboratory studies do not indicate any abnormalities in terms of renal function. He does not have any significant cardiac disease. He has a medium build. He had prostate cancer and underwent a successful radical prostatectomy 10 years ago. His PSA is undetectable. He has some urinary incontinence and wears two pads/day. He underwent the appropriate investigations for gross hematuria. A CT scan of the abdomen and pelvis was normal with the exception of a 4-cm posterior mass in the bladder. There was no hydronephrosis and no enlarged lymph nodes. He underwent a transurethral resection of a solitary bladder tumor performed by another urologist. The tumor was described as large and sessile. It was located on the posterior wall and was approximately 4 cm. The bimanual examination did not reveal a mass. The pathology report stated that the tumor was a high-grade urothelial carcinoma with invasion into the muscularis propria. There was no lymphovascular invasion. I performed a reTURBT, and at that procedure, I did not identify any obvious tumor but the prior resection site was evident. I resected the prior tumor site quite extensively both in depth and width. The pathology revealed only focal carcinoma in situ. There was ample muscle in the specimen and there was some fat as well. As stated, they were free of any cancer. The patient is receptive to any treatment approach.

  20. Ct2 Bladder Cancer.

    PubMed

    Soloway, Mark S

    2016-09-01

    The patient is an 80-year-old man who presented with gross hematuria. His past medical history indicates he was a cigarette smoker with 50 pack/years. He was successfully treated for carcinoma of the lung 7 years ago. He received chemotherapy, radiation, and surgery. He has mild COPD but has a good performance status. His laboratory studies do not indicate any abnormalities in terms of renal function. He does not have any significant cardiac disease. He has a medium build. He had prostate cancer and underwent a successful radical prostatectomy 10 years ago. His PSA is undetectable. He has some urinary incontinence and wears two pads/day. He underwent the appropriate investigations for gross hematuria. A CT scan of the abdomen and pelvis was normal with the exception of a 4-cm posterior mass in the bladder. There was no hydronephrosis and no enlarged lymph nodes. He underwent a transurethral resection of a solitary bladder tumor performed by another urologist. The tumor was described as large and sessile. It was located on the posterior wall and was approximately 4 cm. The bimanual examination did not reveal a mass. The pathology report stated that the tumor was a high-grade urothelial carcinoma with invasion into the muscularis propria. There was no lymphovascular invasion. I performed a reTURBT, and at that procedure, I did not identify any obvious tumor but the prior resection site was evident. I resected the prior tumor site quite extensively both in depth and width. The pathology revealed only focal carcinoma in situ. There was ample muscle in the specimen and there was some fat as well. As stated, they were free of any cancer. The patient is receptive to any treatment approach. PMID:27457483

  1. Biomarkers for bladder cancer management: present and future

    PubMed Central

    Ye, Fei; Wang, Li; Castillo-Martin, Mireia; McBride, Russell; Galsky, Matthew D; Zhu, Jun; Boffetta, Paolo; Zhang, David Y; Cordon-Cardo, Carlos

    2014-01-01

    Accurate and sensitive detection of bladder cancer is critical to diagnose this deadly disease at an early stage, estimate prognosis, predict response to treatment, and monitor recurrence. In past years, laboratory diagnosis and surveillance of urinary bladder cancer have improved significantly. Although urine cytology remains the gold standard test, many new urinary biomarkers have been identified. Furthermore, recent advances in genomic studies of bladder cancer have helped to refine our understanding of the pathogenesis of the disease, the biological basis for outcome disparities, and to inform more efficient treatment and surveillance strategies. In this article, the established diagnostic tests, newly identified biomarkers and genomic landscape of bladder cancer will be reviewed. PMID:25374904

  2. 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.

  3. 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.

  4. [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.

  5. Diagnosis and treatment of bladder cancer: how can we improve?

    PubMed

    Gorin, Michael A; Ayyathurai, Rajinikanth; Soloway, Mark S

    2012-05-01

    The majority of patients with bladder cancer will be diagnosed following an episode of hematuria. With few exceptions, these patients should be referred for a complete urologic evaluation, including a history and physical examination, flexible cystoscopy, imaging of the upper urinary tract, and optional urine cytology. Those found to have a bladder tumor should undergo transurethral resection for the combined purposes of initial staging and treatment. Delays in diagnosing invasive bladder cancer are associated with adverse outcomes. In this review, we cover the diagnosis and management of bladder cancer. In addition, we discuss ways to improve outcomes through increased public awareness, improvements in tumor detection, accurate staging, and regimented patient surveillance.

  6. Urothelial Bladder Cancer Urinary Biomarkers

    PubMed Central

    Noon, Aidan P

    2014-01-01

    Abstract Urothelial bladder cancer is the fourth most prevalent male malignancy in the United States and also one of the ten most lethal. Superficial or non-muscle-invasive bladder cancer has a high rate of recurrence and can progress to muscle invasive disease. Conventional surveillance requires regular cystoscopy and is used often with urinary cytology. Unfortunately, the cystoscopy procedure is invasive for patients and costly for health care providers. Urinary biomarkers have the potential to improve bladder cancer diagnosis, the efficiency and also the cost-effectiveness of follow up. It may also be possible for urinary biomarkers to help prognosticate particularly for patients with high-grade bladder cancer who may want enhanced assessment of their risk of disease progression. In this review the important historical urinary biomarkers and the newly emerging biomarkers are discussed. As will be presented, although many of the tests have good performance characteristics, unfortunately no single test can fulfill all the roles currently provided by cystoscopy and cytology. It is likely that in the future, urinary biomarker testing will be used selectively in a personalized manner to try and improve prognostication or reduce the necessity for invasive cystoscopy in patients understanding the limits of the test.

  7. Metabolic phenotype of bladder cancer.

    PubMed

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

    2016-04-01

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

  8. Metabolic phenotype of bladder cancer.

    PubMed

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

    2016-04-01

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

  9. Early diagnosis of bladder cancer through the detection of urinary tyrosine-phosphorylated proteins

    PubMed Central

    Khadjavi, A; Mannu, F; Destefanis, P; Sacerdote, C; Battaglia, A; Allasia, M; Fontana, D; Frea, B; Polidoro, S; Fiorito, G; Matullo, G; Pantaleo, A; Notarpietro, A; Prato, M; Castagno, F; Vineis, P; Gontero, P; Giribaldi, G; Turrini, F

    2015-01-01

    Background: A noninvasive, highly sensitive and specific urine test is needed for bladder cancer (BC) diagnosis and surveillance in addition to the invasive cystoscopy. We previously described the diagnostic effectiveness of urinary tyrosine-phosphorylated proteins (UPY) and a new assay (UPY-A) for their measurement in a pilot study. The aim of this work was to evaluate the performances of the UPY-A using an independent cohort of 262 subjects. Methods: Urinary tyrosine-phosphorylated proteins were measured by UPY-A test. The area under ROC curve, cutoff, sensitivity, specificity and predictive values of UPY-A were determined. The association of UPY levels with tumour staging, grading, recurrence and progression risk was analysed by Kruskal–Wallis and Wilcoxon's test. To test the probability to be a case if positive at the UPY-A, a logistic test adjusted for possible confounding factor was used. Results: Results showed a significant difference of UPY levels between patients with BC vs healthy controls. For the best cutoff value, 261.26 Standard Units (SU), the sensitivity of the assay was 80.43% and the specificity was 78.82%. A statistically significant difference was found in the levels of UPY at different BC stages and grades between Ta and T1 and with different risk of recurrence and progression. A statistically significant increased risk for BC at UPY-A ⩾261.26 SU was observed. Conclusions: The present study supplies important information on the diagnostic characteristics of UPY-A revealing remarkable performances for early stages and allowing its potential use for different applications encompassing the screening of high-risk subjects, primary diagnosis and posttreatment surveillance. PMID:26125446

  10. [Specific types of bladder cancer].

    PubMed

    Bertz, S; Hartmann, A; Knüchel-Clarke, R; Gaisa, N T

    2016-02-01

    Bladder cancer shows rare variants and special subtypes with diverse prognostic importance and therefore may necessitate different therapeutic approaches. For pathologists it is important to histologically diagnose and specify such variants. Nested variants of urothelial carcinoma with inconspicuous, well-formed tumor cell nests present with an aggressive course. The plasmacytoid variant, which morphologically resembles plasma cells is associated with a shorter survival time and a high frequency of peritoneal metastasis. Micropapillary urothelial carcinoma with small papillary tumor cell islands within artificial tissue retraction spaces and frequent lymphovascular invasion also has a poor prognosis. Other important rare differential variants listed in the World Health Organization (WHO) classification are microcystic, lymphoepithelioma-like, sarcomatoid, giant cell and undifferentiated urothelial carcinomas. Additionally, there are three special types of bladder cancer: squamous cell carcinoma, adenocarcinoma and small cell neuroendocrine carcinoma of the bladder. These tumors are characterized by pure squamous cell or glandular differentiation and are sometimes less responsive to adjuvant (chemo)therapy. Small cell carcinoma of the bladder mimics the neuroendocrine features of its pulmonary counterpart, shows an aggressive course but is sensitive to (neo-)adjuvant chemotherapy. The morphology and histology of the most important variants and special types are discussed in this review. PMID:26782034

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

    PubMed Central

    2013-01-01

    Bladder cancer is the commonest malignancy of the urinary tract. In this review, we look at the latest developments in the diagnosis and management of this condition. Cystoscopy and urine cytology are the most important tools in the diagnosis and follow-up of bladder cancer. Various alternatives have been investigated, either to reduce the frequency of cystoscopy, or improve its sensitivity for detection of tumors. These include urine-based markers and point-of-care tests. Narrow-band imaging and photodynamic diagnosis/blue-light cystoscopy have shown promise in improving detection and reducing recurrence of bladder tumors, by improving the completion of bladder resection when compared with standard resection in white light. The majority of patients with a new diagnosis of bladder cancer have non-muscle-invasive bladder cancer, which requires adjuvant intravesical chemotherapy and/or immunotherapy. Recent developments in post-resection intravesical regimens are discussed. For patients with muscle-invasive bladder cancer, both laparoscopic radical cystectomy and robot-assisted radical cystectomy have been shown to reduce peri-operative morbidity, while being oncologically equivalent to open radical cystectomy in the medium term. Bladder-preserving strategies entail resection and chemoradiation, and in selected patients give equivalent results to surgery. The development, advantages, and disadvantages of these newer approaches are also discussed. PMID:23327481

  12. 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. PMID:21678399

  13. What Is Bladder Cancer?

    MedlinePlus

    ... Urothelial carcinoma, also known as transitional cell carcinoma (TCC), is by far the most common type of ... cancer (other than sarcoma) are treated similar to TCCs, especially for early stage tumors, but if chemotherapy ...

  14. 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

  15. 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

  16. 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.

  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. 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

  19. Stepwise Application of Urine Markers to Detect Tumor Recurrence in Patients Undergoing Surveillance for Non-Muscle-Invasive Bladder Cancer

    PubMed Central

    Todenhöfer, Tilman; Hennenlotter, Jörg; Esser, Michael; Mohrhardt, Sarah; Aufderklamm, Stefan; Böttge, Johannes; Rausch, Steffen; Mischinger, Johannes; Gakis, Georgios; Kuehs, Ursula; Schwentner, Christian

    2014-01-01

    Background. The optimal use of urine markers in the surveillance of non-muscle-invasive bladder cancer (NMIBC) remains unclear. Aim of the present study was to investigate the combined and stepwise use of the four most broadly available urine markers to detect tumor recurrence in patients undergoing surveillance of NMIBC. Patients and Methods. 483 patients with history of NMIBC were included. Cytology, UroVysion, fluorescence in situ hybridization (FISH), immunocytology (uCyt+), and NMP22 ELISA were performed before surveillance cystoscopy. Characteristics of single tests and combinations were assessed by contingency analysis. Results. 128 (26.5%) patients had evidence of tumor recurrence. Sensitivities and negative predictive values (NPVs) of the single tests ranged between 66.4–74.3 and 82.3–88.2%. Two-marker combinations showed sensitivities and NPVs of 80.5–89.8 and 89.5–91.2%. A stepwise application of the two-test combinations with highest accuracy (cytology and FISH; cytology and uCyt+; uCyt+ and FISH) showed NPVs for high-risk recurrences (G3/Cis/pT1) of 98.8, 98.8, and 99.1%, respectively. Conclusions. Combinations of cytology, FISH, immunocytology, and NMP22 show remarkable detection rates for recurrent NMIBC. Stepwise two-test combinations of cytology, FISH, and immunocytology have a low probability of missing a high-risk tumor. The high sensitivities may justify the use of these combinations in prospective studies assessing the use of urine markers to individualize intervals between cystoscopies during follow-up. PMID:25587206

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

    ClinicalTrials.gov

    2016-06-09

    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

  1. [Management of metastatic bladder cancer].

    PubMed

    Gauthier, Hélène; Serrate, Camille; Pouessel, Damien; Le Maignan, Christine; Teixeira, Luis; Culine, Stéphane

    2014-12-01

    The management of patients with metastatic bladder cancer is mainly based on cytotoxic chemotherapy. The reference molecule is cisplatin. In 2014, first-line regimens include gemcitabine and cisplatin (GC protocol) or methotrexate, vinblastine, and cisplatin doxorubicin (MVAC protocol). When cisplatin is contra-indicated, another platinum Salt, carboplatin, is used in combination with gemcitabine. Vinflunine is the only molecule to have obtained a marketing approval for patients who failed first-line chemotherapy including a platinum salt. The overall prognosis of patients remains dismal, since the median overall survival is 12 to 14 months for patients being treated with cisplatin, whereas it is less than 1 year for patients receiving carboplatin. The identification of new effective drugs is a major challenge for the coming years. PMID:25668832

  2. 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.

  3. Protein expression profile related to cisplatin resistance in bladder cancer cell lines detected by two-dimensional gel electrophoresis.

    PubMed

    Taoka, Yoshinori; Matsumoto, Kazumasa; Ohashi, Kazuya; Minamida, Satoru; Hagiwara, Masahiro; Nagi, Shoji; Saito, Tatsuya; Kodera, Yoshio; Iwamura, Masatsugu

    2015-01-01

    We used a proteomic approach to compare the differentially regulated protein expression profiles of cisplatin-naïve and cisplatin-resistant bladder cancer cell lines to screen candidate molecules related to cisplatin resistance. The cisplatin-resistant cell line T24 was established by the stepwise exposure of T24 cells to up to 40 μM of cisplatin. We performed a comprehensive study of protein expression in bladder cancer cell lines that included cisplatin-naïve (T24) and cisplatin-resistant cells (T24CDDPR) by means of agarose two-dimensional gel electrophoresis followed by analysis of liquid chromatography tandem mass spectroscopy. We identified 25 obviously different spots for T24 and T24 CDDPR. Seven spots had increased expression and 18 spots had decreased expression in T24CDDPR compared to those in T24. Cytoskeletal proteins and enzyme modulators were prominent among differential proteins. Of the 25 proteins, we selected HNRNPA3, PCK2, PPL, PGK1, TKT, SERPINB2, GOT2, and EIF3A for further validation by Western blot. HNRNPA3, PGK1, TKT, and SERPINB2 had more than 1.5-times incremental expression in T24CDDPR compared to that in T24. PCK2 and PPL expressions were decreased less than 20% in T24CDDPR compared to that in T24. The results of 25 new proteins in this study could be valuable and could lead to the development of a new molecular marker. PMID:26299484

  4. CIP2A protein expression in high-grade, high-stage bladder cancer

    PubMed Central

    Huang, Lisa P; Savoly, Diana; Sidi, Abraham A; Adelson, Martin E; Mordechai, Eli; Trama, Jason P

    2012-01-01

    Bladder cancer is one of the most common cancers in the United States. Numerous markers have been evaluated for suitability of bladder cancer detection and surveillance. However, few of them are acceptable as a routine tool. Therefore, there exists a continuing need for an assay that detects the presence of bladder cancer in humans. It would be advantageous to develop an assay with a protein that is associated with the development of bladder cancer. We have identified the cancerous inhibitor of PP2A (CIP2A) protein as a novel bladder cancer biomarker. In this study, Western blot analysis was used to assess the expression level of CIP2A protein in bladder cancer cell lines and bladder cancer patient tissues (n = 43). Our studies indicated CIP2A protein was abundantly expressed in bladder cancer cell lines but not in nontumor epithelial cell lines. Furthermore, CIP2A was specifically expressed in transitional cell carcinoma (TCC) of the bladder tumor tissues but not in adjacent nontumor bladder tissue. Our data showed that CIP2A protein detection in high-grade TCC tissues had a sensitivity of 65%, which is 3.4-fold higher than that seen in low-grade TCC tissues (19%). The level of CIP2A protein expression increased with the stage of disease (12%, 27%, 67%, and 100% for pTa, pT1, pT2, and pT3 tumor, respectively). In conclusion, our studies suggest that CIP2A protein is specifically expressed in human bladder tumors. CIP2A is preferentially expressed in high-grade and high-stage TCC tumors, which are high-risk and invasive tumors. Our studies reported here support the role of CIP2A in bladder cancer progression and its usefulness for the surveillance of recurrence or progression of human bladder cancer. PMID:23342256

  5. 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

  6. Computer-aided detection of bladder tumors based on the thickness mapping of bladder wall in MR images

    NASA Astrophysics Data System (ADS)

    Zhu, Hongbin; Duan, Chaijie; Jiang, Ruirui; Li, Lihong; Fan, Yi; Yu, Xiaokang; Zeng, Wei; Gu, Xianfeng; Liang, Zhengrong

    2010-03-01

    Bladder cancer is reported to be the fifth leading cause of cancer deaths in the United States. Recent advances in medical imaging technologies, such as magnetic resonance (MR) imaging, make virtual cystoscopy a potential alternative with advantages as being a safe and non-invasive method for evaluation of the entire bladder and detection of abnormalities. To help reducing the interpretation time and reading fatigue of the readers or radiologists, we introduce a computer-aided detection scheme based on the thickness mapping of the bladder wall since locally-thickened bladder wall often appears around tumors. In the thickness mapping method, the path used to measure the thickness can be determined without any ambiguity by tracing the gradient direction of the potential field between the inner and outer borders of the bladder wall. The thickness mapping of the three-dimensional inner border surface of the bladder is then flattened to a twodimensional (2D) gray image with conformal mapping method. In the 2D flattened image, a blob detector is applied to detect the abnormalities, which are actually the thickened bladder wall indicating bladder lesions. Such scheme was tested on two MR datasets, one from a healthy volunteer and the other from a patient with a tumor. The result is preliminary, but very promising with 100% detection sensitivity at 7 FPs per case.

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

    PubMed

    Ishizu, Sumiko; Hashida, Chise

    2007-01-01

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

  8. 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

  9. [Epidemiological investigation on bladder cancer and occupations].

    PubMed

    Obata, K; Ohno, Y; Aoki, K

    1989-12-01

    A population-based case-control study was conducted in Boston, U.S.A., Manchester, U.K., and Nagoya, Japan to assess the associations of occupations with bladder cancer in men. In Nagoya, cancer cases were identified through Nagoya Bladder Cancer Registry, and controls were randomly selected from the general population using electoral registers. Study subjects, all males, analyzed were 430 cases and 397 controls in Boston; 339 and 493 in Manchester, and 220 and 443 in Nagoya, respectively. Occupations significantly related to an increased bladder cancer risk were those manufacturing or handling dyes, leather, paint or organic chemicals in Boston, and leather or medical workers in Manchester. Occupations significantly associated with bladder cancer development were not found in Nagoya. In general, risk related to occupations was relatively higher in the younger age group (less than 65 years old) than in the older age group (greater than or equal to 65 yrs old). Statistically significant differences in bladder cancer risk were not demonstrated between manufacturing workers and service workers.

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

    PubMed Central

    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. PMID:26151138

  11. 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.

  12. Optimizing systemic therapy for bladder cancer.

    PubMed

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

    2013-07-01

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

  13. 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

  14. Targeting glycogen metabolism in bladder cancer.

    PubMed

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

    2015-07-01

    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.

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

    ClinicalTrials.gov

    2016-09-12

    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

  16. Oncoprotein DEK as a tissue and urinary biomarker for bladder cancer

    PubMed Central

    2011-01-01

    Background Bladder cancer is a significant healthcare problem in the United States of America with a high recurrence rate. Early detection of bladder cancer is essential for removing the tumor with preservation of the bladder, avoiding metastasis and hence improving prognosis and long-term survival. The objective of this study was to analyze the presence of DEK protein in voided urine of bladder cancer patients as a urine-based bladder cancer diagnostic test. Methods We examined the expression of DEK protein by western blot in 38 paired transitional cell carcinoma (TCC) bladder tumor tissues and adjacent normal tissue. The presence of DEK protein in voided urine was analyzed by western blot in 42 urine samples collected from patients with active TCC, other malignant urogenital disease and healthy individuals. Results The DEK protein is expressed in 33 of 38 bladder tumor tissues with no expression in adjacent normal tissue. Based on our sample size, DEK protein is expressed in 100% of tumors of low malignant potential, 92% of tumors of low grade and in 71% of tumors of high grade. Next, we analyzed 42 urine samples from patients with active TCC, other malignant urogenital disease, non-malignant urogenital disease and healthy individuals for DEK protein expression by western blot analysis. We are the first to show that the DEK protein is present in the urine of bladder cancer patients. Approximately 84% of TCC patient urine specimens were positive for urine DEK. Conclusion Based on our pilot study of 38 bladder tumor tissue and 42 urine samples from patients with active TCC, other malignant urogenital disease, non-malignant urogenital disease and healthy individuals; DEK protein is expressed in bladder tumor tissue and voided urine of bladder cancer patients. The presence of DEK protein in voided urine is potentially a suitable biomarker for bladder cancer and that the screening for the presence of DEK protein in urine can be explored as a noninvasive diagnostic

  17. 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

  18. SKIP expression is correlated with clinical prognosis in patients with bladder cancer

    PubMed Central

    Wang, Longwang; Zhang, Mei; Wu, Yong; Cheng, Cheng; Huang, Yawei; Shi, Zimin; Huang, Hongwei

    2014-01-01

    The Ski-interacting protein (SKIP) is a transcriptional cofactor distinct from other cofactors and is involved in regulation of many cancer-related proteins. However, its distribution and clinical significances in bladder cancer remains poorly understood. In this study, Quantitative real-time PCR and immunohistochemistry were performed to detect the expression of SKIP in clinical bladder cancer samples. In addition, the correlation of SKIP expression and clinicopathological features and clinical outcomes were analyzed. The expression levels of SKIP in clinical bladder cancer were much higher than that in paired adjacent noncancerous tissues. High expression of SKIP was closely related with histological grades and the poor prognosis of bladder cancer. Based on our data, we speculated that SKIP may be a potential prognostic marker in bladder cancer. PMID:24817966

  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. Detection of numerical chromosome aberrations using in situ hybridization in paraffin sections of routinely processed bladder cancers.

    PubMed

    Hopman, A H; van Hooren, E; van de Kaa, C A; Vooijs, P G; Ramaekers, F C

    1991-07-01

    An improved protocol for in situ hybridization (ISH) to routinely processed, paraffin-imbedded tissue sections from transitional bladder carcinoma (TCC) is presented. The protocol to detect numerical chromosome aberrations involved treatment of sections with thiocyanate prior to proteolytic digestion, resulting in reproducible ISH reactions. It was used to explore the influence of nuclear truncation in the detection of numerical chromosome aberrations and the detection of tumor cells among stromal and inflammatory cells, to compare the flow cytometric DNA index with chromosome copy number, and to study chromosome heterogeneity within tumors. For this study, a DNA probe for the chromosome region 1q12 was used. Hybridization of model systems with known chromosome numbers, such as sections of paraffin-embedded lymph nodes, paraffin-embedded human peripheral lymphocytes, T24 and Molt-4 cells with two, three, and four chromosomes 1, respectively, showed in at least 50% of the cells the proper number of chromosome hybridization signals in standard 6-microns-thick sections. Depending on the size of the nucleus, a certain percentage of the cells showed lower copy numbers as a result of truncation. In four cases of normal urothelium in paraffin sections, the percentage of nuclei with more than two chromosome spots did not exceed 5%. Comparison of the number of ISH signals, as detected in ethanol-fixed single cell suspensions of 11 TCCs [five flow cytometric (FCM) diploid, three FCM aneuploid, and three FCM tetraploid], with ISH results obtained in paraffin sections of the same tumors showed that typical numerical chromosome aberrations, such as trisomy and tetrasomy up to nonasomy, could be detected. However, the real chromosome copy number is underestimated, especially in tumors with high copy numbers, as detected in the single cell suspensions of the same tumors. Hybridization of a TCC with extremely large nuclei (DNA index = 3.2) containing six to nine ISH signals as

  2. 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

  3. Bladder cancer: clinical and pathological profile.

    PubMed

    Lopez-Beltran, Antonio

    2008-09-01

    Bladder tumours represent a heterogeneous group of cancers. The natural history of these bladder cancers is that of recurrence of disease and progression to higher grade and stage disease. Furthermore, recurrence and progression rates of superficial bladder cancer vary according to several tumour characteristics, mainly tumour grade and stage. The most recent World Health Organization (WHO) classification of tumours of the urinary system includes urothelial flat lesions: flat hyperplasia, dysplasia and carcinoma in situ. The papillary lesions are broadly subdivided into benign (papilloma and inverted papilloma), papillary urothelial neoplasia of low malignant potential (PUNLMP) and non-invasive papillary carcinoma (low or high grade). The initial proposal of the 2004 WHO has been achieved, with most reports supporting that categories are better defined than in previous classifications. An additional important issue is that PUNLMP, the most controversial proposal of the WHO in 2004, has lower malignant behaviour than low-grade carcinoma. Whether PUNLMP remains a clinically useful category, or whether this category should be expanded to include all low-grade, stage Ta lesions (PUNLMP and low-grade papillary carcinoma) as a wider category of less aggressive tumours not labelled as cancer, needs to be discussed in the near future. This article summarizes the recent literature concerning important issues in the pathology and the clinical management of patients with bladder urothelial carcinoma. Emphasis is placed on clinical presentation, the significance of haematuria, macroscopic appearance (papillary, solid or mixed, single or multiple) and synchronous or metachronous presentation (field disease vs monoclonal disease with seeding), classification and microscopic variations of bladder cancer with clinical significance, TNM distribution and the pathological grading according to the 2004 WHO proposal.

  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. 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

  6. 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. PMID:21990318

  7. Direct quantitative detection for cell-free miR-155 in urine: a potential role in diagnosis and prognosis for non-muscle invasive bladder cancer

    PubMed Central

    Zhang, Xin; Zhang, Yanli; Liu, Xinfeng; Fang, Aiju; Wang, Jinfeng; Yang, Yongmei; Wang, Lili; Du, Lutao; Wang, Chuanxin

    2016-01-01

    High recurrence rates of non-muscle invasive bladder cancer (NMIBC) in patients require lifelong testing and monitoring. The aim of this study is to develop a simplified RT-qPCR method (RT-qPCR-D) which directly quantifies cell-free miR-155 in urine without RNA extraction, and assess it as a potential tool in NMIBC detection. A pilot study including 60 urine samples was used to investigate the feasibility of RT-qPCR-D in detecting cell-free miR-155. Then, miR-155 levels were quantified in a large independent cohort of urine from 162 NIMBC patients, 76 cystitis patients, and 86 healthy donors using the RT-qPCR-D method. Changes of cell-free miR-155 before and after operation were also analyzed in 32 NIMBC patients. In pilot study, we found a significant linear association between RT-qPCR and RT-qPCR-D in urinary miR-155 detection. Both methods showed cell-free miR-155 were significantly increased in NMIBC patients, and could reflect their expression in tissues. Then, the increased expression of cell-free miR-155 was successfully validated in 162 NIMBC patients when compared with cystitis patients and healthy donors. Moreover, it distinguished NMIBC patients from others with 80.2% sensitivity and 84.6% specificity, which was superior to urine cytology. Cell-free miR-155 correlated with NMIBC stage and grade, and was an independent factor for predicting recurrence and progression to muscle invasion. In addition, cell-free miR-155 was significantly decreased after NMIBC patients underwent transurethral bladder resection. In conclusion, detection of cell-free miR-155 in urine using RT-qPCR-D is a simple and noninvasive approach which may be used for NMIBC diagnosis and prognosis prediction. PMID:26657502

  8. Novel therapeutic approaches for recurrent nonmuscle invasive bladder cancer.

    PubMed

    Boehm, Brock E; Svatek, Robert S

    2015-05-01

    This article summarizes strategies being investigated in patients with nonmuscle invasive bladder cancer. Progress has been made toward improving the delivery method of intravesical agents. Intravesical therapy is limited by the amount of time that the agent remains in contact with the bladder. Bladder cancer is considered to be responsive to immune therapy. Thus, many novel approaches are immune-based therapies and include cancer vaccines, use of Bacillus Calmette-Guérin (BCG) subcomponents, and checkpoint inhibitors. Finally, access to bladder mucosa via direct catheterization into the bladder via the urethra has enabled unique strategies for delivery of cancer therapy including viral- or plasmid-based gene therapy.

  9. 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

  10. Urothelial bladder cancer with cavitary lung metastases.

    PubMed

    Kurian, Anil; Lee, Jason; Born, Abraham

    2011-01-01

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

  11. [Case of heterochronous triple urogenital cancer (renal cell carcinoma, bladder cancer, prostatic cancer)].

    PubMed

    Okumura, Akiou; Tsuritani, Shinji; Takagawa, Kiyoshi; Fuse, Hideki

    2013-11-01

    We report a case of a 73-year-old male with heterochronous triple urogenital cancer. The patient was referred to our hospital because serum PSA was elevated (7.0 ng/ml) in 1998. Prostatic needle biopsy revealed prostatic cancer in the right lobe, and total prostatectomy was performed. The histopathological diagnosis was moderately differentiated adenocarcinoma (TlcNOMO). Non-muscle invasive bladder cancer (NMIBC) was detected during an examination for microhematuria in 2002. Transurethral resection of the bladder tumor (TURBT) procedure was performed, and the histopathological diagnosis was grade 2 urothelial carcinoma (pTa). A right renal mass was detected incidentally on follow-up CT for bladder cancer in 2008. Renal enucleation was performed in 2009. The histopathological diagnosis was grade 2 clear cell renal cell carcinoma (pTlaNXMO). NMIBC was detected on follow-up urethrocystoscopy in 2011. The TURBT procedure was performed, and the histopathological diagnosis was grade 2 urothelial carcinoma (pTa). On follow-up for urogenital cancer patients, it is important to investigate recurrence of the primary cancer and also heterochronous canceration of other urogenital organs.

  12. Changes in autofluorescence based organoid model of muscle invasive urinary bladder cancer

    PubMed Central

    Palmer, Scott; Litvinova, Karina; Dunaev, Andrey; Fleming, Stewart; McGloin, David; Nabi, Ghulam

    2016-01-01

    Muscle invasive urinary bladder cancer is one of the most lethal cancers and its detection at the time of transurethral resection remains limited and diagnostic methods are urgently needed. We have developed a muscle invasive transitional cell carcinoma (TCC) model of the bladder using porcine bladder scaffold and the human bladder cancer cell line 5637. The progression of implanted cancer cells to muscle invasion can be monitored by measuring changes in the spectrum of endogenous fluorophores such as reduced nicotinamide dinucleotide (NADH) and flavins. We believe this could act as a useful tool for the study of fluorescence dynamics of developing muscle invasive bladder cancer in patients. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI. PMID:27446646

  13. Changes in autofluorescence based organoid model of muscle invasive urinary bladder cancer.

    PubMed

    Palmer, Scott; Litvinova, Karina; Dunaev, Andrey; Fleming, Stewart; McGloin, David; Nabi, Ghulam

    2016-04-01

    Muscle invasive urinary bladder cancer is one of the most lethal cancers and its detection at the time of transurethral resection remains limited and diagnostic methods are urgently needed. We have developed a muscle invasive transitional cell carcinoma (TCC) model of the bladder using porcine bladder scaffold and the human bladder cancer cell line 5637. The progression of implanted cancer cells to muscle invasion can be monitored by measuring changes in the spectrum of endogenous fluorophores such as reduced nicotinamide dinucleotide (NADH) and flavins. We believe this could act as a useful tool for the study of fluorescence dynamics of developing muscle invasive bladder cancer in patients. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI. PMID:27446646

  14. Hyperthermia as a treatment for bladder cancer.

    PubMed

    Rampersaud, Edward N; Vujaskovic, Zeljko; Inman, Brant A

    2010-11-15

    Modern cancer care is characterized by a focus on organ-sparing multi-modal treatments. In the case of non-muscle-invasive bladder cancer this is particularly true; treatment is focused on reducing the frequency of low-risk recurrences and preventing high-risk progression. Deep regional hyperthermia is an oncologic therapeutic modality that can help achieve these two goals. The combination of hyperthermia with chemotherapy and radiotherapy has improved patient outcomes in several tumor types. In this review, we highlight the biology of therapeutic fever-range hyperthermia, discuss how hyperthermia is administered and dosed, demonstrate how heat can be added to other treatment regimens, and summarize the data supporting the role of hyperthermia in the management of bladder cancer.

  15. Bladder cancer: approaches to prevention and control.

    PubMed

    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.

  16. HAL fluorescence cystoscopy: towards a new paradigm in bladder cancer management

    NASA Astrophysics Data System (ADS)

    Jichlinski, Patrice

    2009-06-01

    Hexaminolevulinate fluorescence cystoscopy by the addition of a specific tissue fluorophore enhances the contrast between benign and malignant epithelial (urothelial) cells in the bladder. Improved detection of flat and papillary tumors as confirmed in recent phase III clinical trials allows the urologist to obtain a precise information on the disease extent at the whole surface of the bladder wall. With gaining experience, management of non muscle invasive bladder cancer improves in readiness and accuracy.

  17. 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

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

    PubMed

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

    2015-04-01

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

  19. [The biochemical carcinogenesis of selected heavy metals in bladder cancer].

    PubMed

    Rorbach-Dolata, Anna; Marchewka, Zofia; Piwowar, Agnieszka

    2015-01-01

    Bladder cancer takes the second place in the classification of morbidity of urinary system cancers. Many chemical factors take part in cancerogenesis. It is suggested that exposure to heavy metals such as arsenic, chromium, nickel and cadmium as well as its metabolites may trigger the bladder cancer through inducing excessive reactive oxygen species production and oxidative stress formation which are responsible for DNA damage. In patients with bladder cancer is observed the disorder of processes regulated by p-53, including apoptosis. There are many patients with bladder cancer with confirmed absence of retinoblastoma protein, which is responsible of holding on the process of coming up the cells with mutation into synthesis, where the replication process undergoes. It is mentioned that excessive expression of proto-oncogenes may also cause the bladder cancer. The article concerns biochemical effects of exposure to chosen heavy metals and their potential role in bladder cancer progression. PMID:26689010

  20. Epigenetic silencing of S100A2 in bladder and head and neck cancers

    PubMed Central

    Lee, Juna; Wysocki, Piotr T.; Topaloglu, Ozlem; Maldonado, Leonel; Brait, Mariana; Begum, Shahnaz; Moon, David; Kim, Myoung Sook; Califano, Joseph A.; Sidransky, David; Hoque, Mohammad O.; Moon, Chulso

    2015-01-01

    S100A2, a member of the S100 protein family, is known to be downregulated in a number of human cancers, leading to its designation as a potential tumor suppressor gene. Here, we investigated the expression and methylation status of S100A2 in head&neck and bladder cancer. Reduced mRNA and protein expression was observed in 8 head&neck and bladder cancer cell lines. To explore the mechanism responsible for the downregulation of S100A2, we treated six cell lines with 5-aza-2′-deoxycytidine. We found S100A2 is silenced in association with aberrant promoter-region methylation and its expression is restored with 5-aza-2′-deoxycytidine treatment. Of 31 primary head&neck cancer cases and 31 bladder cancer cases, promoter methylation was detected in 90% and 80% of cases, respectively. Interestingly, only 1/9 of normal head&neck tissues and 2/6 of normal bladder tissues showed promoter methylation. S100A2 promoter methylation can be detected in urine and is more frequent in bladder cancer patients than in healthy subjects (96% vs 48% respectively). Moreover, increased methylation of S100A2 is linked to the progression of the tumor in bladder cancer (p<0.01). Together, this data shows that methylation-associated inactivation of S100A2 is frequent and may be an important event in the tumorigenesis of head&neck and bladder cancer. PMID:26097874

  1. 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

  2. Paraneoplastic retinopathy associated with occult bladder cancer

    PubMed Central

    Nivean, M; Muttuvelu, Danson V; Afzelius, Pia; Berman, Dalia C

    2016-01-01

    The aim was to report the first case of cancer-associated retinopathy (CAR) presenting before bladder cancer diagnosis. A 71-year-old woman with a history of bilateral vision loss underwent subsequent complete ophthalmic examination include a fluorescein angiography, full-field electroretinogram (ERG), serology including serum antibodies for CAR, and positron emission tomography-computed tomography (PET-CT) scan. The patient was diagnosed with bladder carcinoma revealed by PET-CT. Timely recognition of this entity may be crucial for an increased patient survival thus adult onset progressive photoreceptor dysfunction, confirmed by ERG, should alert to a possible remote effect of known or occult malignancy. In the latter, PET-CT may be exploited as a powerful diagnostic tool. PMID:27146943

  3. Paraneoplastic retinopathy associated with occult bladder cancer.

    PubMed

    Nivean, M; Muttuvelu, Danson V; Afzelius, Pia; Berman, Dalia C

    2016-03-01

    The aim was to report the first case of cancer-associated retinopathy (CAR) presenting before bladder cancer diagnosis. A 71-year-old woman with a history of bilateral vision loss underwent subsequent complete ophthalmic examination include a fluorescein angiography, full-field electroretinogram (ERG), serology including serum antibodies for CAR, and positron emission tomography-computed tomography (PET-CT) scan. The patient was diagnosed with bladder carcinoma revealed by PET-CT. Timely recognition of this entity may be crucial for an increased patient survival thus adult onset progressive photoreceptor dysfunction, confirmed by ERG, should alert to a possible remote effect of known or occult malignancy. In the latter, PET-CT may be exploited as a powerful diagnostic tool. PMID:27146943

  4. Dose Distribution in Bladder and Surrounding Normal Tissues in Relation to Bladder Volume in Conformal Radiotherapy for Bladder Cancer

    SciTech Connect

    Majewski, Wojciech; Wesolowska, Iwona; Urbanczyk, Hubert; Hawrylewicz, Leszek; Schwierczok, Barbara; Miszczyk, Leszek

    2009-12-01

    Purpose: To estimate bladder movements and changes in dose distribution in the bladder and surrounding tissues associated with changes in bladder filling and to estimate the internal treatment margins. Methods and Materials: A total of 16 patients with bladder cancer underwent planning computed tomography scans with 80- and 150-mL bladder volumes. The bladder displacements associated with the change in volume were measured. Each patient had treatment plans constructed for a 'partially empty' (80 mL) and a 'partially full' (150 mL) bladder. An additional plan was constructed for tumor irradiation alone. A subsequent 9 patients underwent sequential weekly computed tomography scanning during radiotherapy to verify the bladder movements and estimate the internal margins. Results: Bladder movements were mainly observed cranially, and the estimated internal margins were nonuniform and largest (>2 cm) anteriorly and cranially. The dose distribution in the bladder worsened if the bladder increased in volume: 70% of patients (11 of 16) would have had bladder underdosed to <95% of the prescribed dose. The dose distribution in the rectum and intestines was better with a 'partially empty' bladder (volume that received >70%, 80%, and 90% of the prescribed dose was 23%, 20%, and 15% for the rectum and 162, 144, 123 cm{sup 3} for the intestines, respectively) than with a 'partially full' bladder (volume that received >70%, 80%, and 90% of the prescribed dose was 28%, 24%, and 18% for the rectum and 180, 158, 136 cm{sup 3} for the intestines, respectively). The change in bladder filling during RT was significant for the dose distribution in the intestines. Tumor irradiation alone was significantly better than whole bladder irradiation in terms of organ sparing. Conclusion: The displacements of the bladder due to volume changes were mainly related to the upper wall. The internal margins should be nonuniform, with the largest margins cranially and anteriorly. The changes in bladder

  5. 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.

  6. Dietary factors associated with bladder cancer

    PubMed Central

    2016-01-01

    It is biologically plausible for dietary factors to influence bladder cancer risk considering that beneficial as well as harmful components of a diet are excreted through the urinary tract and in direct contact with the epithelium of the bladder. However, studies that investigated the association between dietary factors and bladder cancer (BC) risk have largely reported inconsistent results. The macronutrient intake and risk of BC could have yield inconsistent results across studies because of lack of details on the type, source and the quantities of different dietary fatty acids consumed. There is evidence to suggest that consumption of processed meat may increase BC risk. Dietary carbohydrate intake does not appear to be directly associated with BC risk. Even though a large number of studies have investigated the association between fruit/vegetable consumption/micronutrients in those and BC risk, they have yielded inconsistent results. Gender-specific subgroup analysis, details of how fruits and vegetables are consumed (raw vs. cooked), adequate control for smoking status/aggressiveness of the cancer and consideration of genetic make-up may clarify these inconsistent results. There is no strong evidence to suggest that supplementation with any common micronutrient is effective in reducing BC risk. These limitations in published research however do not totally eclipse the observation that a diet rich in fruits and vegetables and low in processed meat along with especially smoking cessation may convey some protective effects against BC risk. PMID:27326403

  7. 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

  8. Ingested arsenic, keratoses, and bladder cancer.

    PubMed

    Cuzick, J; Sasieni, P; Evans, S

    1992-08-15

    A cohort of 478 patients treated with Fowler's solution (potassium arsenite) in Lancashire, England, during the period 1945-1969 and previously followed until January 1, 1980, was followed for an additional 11 years. A significant excess of bladder cancer mortality occurred (observed/expected ratio = 5/1.6; p = 0.05). No excess was found for other causes of death. In a subcohort of 142 patients examined for signs of arsenicism around 1970, all 11 subsequent cancer deaths occurred in those with signs of arsenicism (p = 0.0009).

  9. 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.

  10. Proteomics Analysis of Bladder Cancer Exosomes*

    PubMed Central

    Welton, Joanne L.; Khanna, Sanjay; Giles, Peter J.; Brennan, Paul; Brewis, Ian A.; Staffurth, John; Mason, Malcolm D.; Clayton, Aled

    2010-01-01

    Exosomes are nanometer-sized vesicles, secreted by various cell types, present in biological fluids that are particularly rich in membrane proteins. Ex vivo analysis of exosomes may provide biomarker discovery platforms and form non-invasive tools for disease diagnosis and monitoring. These vesicles have never before been studied in the context of bladder cancer, a major malignancy of the urological tract. We present the first proteomics analysis of bladder cancer cell exosomes. Using ultracentrifugation on a sucrose cushion, exosomes were highly purified from cultured HT1376 bladder cancer cells and verified as low in contaminants by Western blotting and flow cytometry of exosome-coated beads. Solubilization in a buffer containing SDS and DTT was essential for achieving proteomics analysis using an LC-MALDI-TOF/TOF MS approach. We report 353 high quality identifications with 72 proteins not previously identified by other human exosome proteomics studies. Overrepresentation analysis to compare this data set with previous exosome proteomics studies (using the ExoCarta database) revealed that the proteome was consistent with that of various exosomes with particular overlap with exosomes of carcinoma origin. Interrogating the Gene Ontology database highlighted a strong association of this proteome with carcinoma of bladder and other sites. The data also highlighted how homology among human leukocyte antigen haplotypes may confound MASCOT designation of major histocompatability complex Class I nomenclature, requiring data from PCR-based human leukocyte antigen haplotyping to clarify anomalous identifications. Validation of 18 MS protein identifications (including basigin, galectin-3, trophoblast glycoprotein (5T4), and others) was performed by a combination of Western blotting, flotation on linear sucrose gradients, and flow cytometry, confirming their exosomal expression. Some were confirmed positive on urinary exosomes from a bladder cancer patient. In summary, the

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

    ClinicalTrials.gov

    2016-05-06

    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

  12. Improving Systemic Chemotherapy for Bladder Cancer.

    PubMed

    Rose, Tracy L; Milowsky, Matthew I

    2016-05-01

    Systemic chemotherapy is integral to the management of muscle-invasive and metastatic bladder cancer (BCa). Neoadjuvant chemotherapy has been increasingly utilized for muscle-invasive BCa over the past several years, and several options for cisplatin-based regimens have emerged. Adjuvant chemotherapy may be considered for select patients who did not receive neoadjuvant therapy. Systemic chemotherapy added to radiotherapy is a critical component of a bladder-preserving approach and superior to radiotherapy alone. Cisplatin-based chemotherapy has been the mainstay for metastatic BCa for more than three decades. Novel targeted agents are in development fueled by the recent molecular characterization of BCa. Recent trials of immunotherapy have demonstrated the possibility of a less toxic and potentially more effective treatment for metastatic disease. It is an extremely exciting time for BCa research, and much needed improvements in systemic treatment are most certainly on the horizon. PMID:26984414

  13. Bladder Cancer Patient Advocacy: A Global Perspective

    PubMed Central

    Quale, Diane Zipursky; Bangs, Rick; Smith, Monica; Guttman, David; Northam, Tammy; Winterbottom, Andrew; Necchi, Andrea; Fiorini, Edoardo; Demkiw, Stephanie

    2015-01-01

    Abstract Over the past 20 years, cancer patient advocacy groups have demonstrated that patient engagement in cancer care is essential to improving patient quality of life and outcomes. Bladder cancer patient advocacy only began 10 years ago in the United States, but is now expanding around the globe with non-profit organizations established in Canada, the United Kingdom and Italy, and efforts underway in Australia. These organizations, at different levels of maturity, are raising awareness of bladder cancer and providing essential information and resources to bladder cancer patients and their families. The patient advocacy organizations are also helping to advance research efforts by funding research proposals and facilitating research collaborations. Strong partnerships between these patient advocates and the bladder cancer medical community are essential to ensuringsustainability for these advocacy organizations, increasing funding to support advances in bladder cancer treatment, and improving patient outcomes. PMID:27398397

  14. [Molecular classification of bladder cancer. Possible similarities to breast cancer].

    PubMed

    Wirtz, R M; Fritz, V; Stöhr, R; Hartmann, A

    2016-02-01

    Therapeutic decisions for breast cancer are increasingly becoming based on subtype-specific gene expression tests. For bladder cancer very similar subtypes have been identified by genome-wide mRNA analysis, which as for breast cancer differ with respect to the prognosis and response to therapy on the basis of their hormone dependency. At the DNA level, however, the type of mutations and their frequencies within the subtypes are strikingly different between bladder and breast cancers. It will be interesting to see whether possible driver mutations can serve as therapeutic targets in both indications. In contrast, the apparent hormone dependency of a substantial number of bladder carcinomas suggests that hormonal and anti-hormonal treatment can be valid therapy options similar to breast cancer. Moreover, gender-specific differences with respect to the incidence and aggressiveness of male compared to female bladder cancers can be explained by hormonal effects. Together with forthcoming immunomodulatory therapies these multiple therapy options raise and give new hope to efficiently combat this aggressive disease. PMID:26780243

  15. Biomarkers for non-muscle invasive bladder cancer: Current tests and future promise

    PubMed Central

    Darwiche, Fadi; Parekh, Dipen J.; Gonzalgo, Mark L.

    2015-01-01

    The search continues for optimal markers that can be utilized to improve bladder cancer detection and to predict disease recurrence. Although no single marker has yet replaced the need to perform cystoscopy and urine cytology, many tests have been evaluated and are being developed. In the future, these promising markers may be incorporated into standard practice to address the challenge of screening in addition to long-term surveillance of patients who have or are at risk for developing bladder cancer. PMID:26604437

  16. 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.

  17. 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.

  18. 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.

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

    PubMed Central

    Tomlinson, Ben; Lin, Tzu-yin; Dall'Era, Marc; Pan, Chong-Xian

    2015-01-01

    Nanotechnology is being developed for the diagnosis and treatment of both nonmyoinvasive bladder cancer (NMIBC) and invasive bladder cancer. The diagnostic applications of nanotechnology in NMIBC mainly focus on tumor identification during endoscopy to increase complete resection of bladder cancer while nanotechnology to capture malignant cells or their components continues to be developed. The therapeutic applications of nanotechnology in NMIBC are to reformulate biological and cytotoxic agents for intravesical instillation, combine both diagnostic and therapeutic application in one nanoformulation. In invasive and advanced bladder cancer, magnetic resonance imaging with supraparamagnetic iron oxide nanoparticles can improve the sensitivity and specificity in detecting small metastasis to lymph nodes. Nanoformulation of cytotoxic agents can potentially decrease the toxicity while increasing efficacy. PMID:25929573

  20. 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.

  1. Narrow band imaging and bladder cancer: when and how.

    PubMed

    Naselli, Angelo; Puppo, Paolo

    2015-10-01

    Narrow band imaging (NBI) is an optical enhancement technology for endoscopy. NBI works filtering the standard white light in two bandwidths of illumination of 415 nm, blue, and 540 nm, green. As a result, capillaries on mucosal surface appear brown and veins in connective subepithelial layer cyan, enhancing the contrast among epithelial, subepithelial tissue and its vascularisation. Given that it is a filter, it is safe, does not need any kind of instillation and the vision modality can be switched from NBI to white light and vice versa without any limitations of time. NBI-assisted cystoscopy increases the detection rate of urothelial lesions and enhances visibility of tumour margins with respect to standard white light modality, although it does not need a particular learning curve. NBI exploration of the bladder should be avoided during active bleeding because the light absorption would be excessive impeding an optimal vision. Moreover, it should always be employed in combination with standard white light modality to avoid an excess of false-positive findings, particularly during or immediately after topic treatments. It can be used in office to anticipate bladder recurrences and in the operating theatre to perform a complete tumour resection. As a matter of fact, it is able to reduce the recurrence rate and ameliorate bladder cancer management by identifying high-grade cancerous tissue, especially Cis, undetected by the standard white light modality. PMID:26481715

  2. Active surveillance for nonmuscle invasive bladder cancer.

    PubMed

    Miyake, Makito; Fujimoto, Kiyohide; Hirao, Yoshihiko

    2016-06-01

    Nonmuscle invasive bladder cancer (NMIBC) is known to be a heterogeneous malignancy that requires varying treatment modalities and follow-up schedules. Low-grade Ta papillary tumors are categorized as low-risk NMIBC because of their favorable prognosis. There is an expanding movement that overdiagnosis and overtreatment should be avoided considering the economic impact and the patients' quality of life. It has been over 10 years since the initial assessment of active surveillance for low-risk NMIBC suggested its feasibility and safety. However, urologists are still unfamiliar with this treatment option, which can be ideal in appropriately selected patients. In this review article, we focus on active surveillance for low-risk NMIBC and discuss the evidence and rationale for this treatment option. There are several issues to resolve in order to advocate active surveillance as a standard option in selected patients. A specific follow-up protocol including intervals of cystoscopy, urine cytology, urine markers, and other radiographic examinations need to be optimized and validated. Finally, we integrate the available data into the follow-up strategy and propose a new surveillance protocol for active surveillance of recurrent low-risk bladder cancer. PMID:27326406

  3. Surgical treatment of gall-bladder cancer.

    PubMed

    Masior, Łukasz; Krasnodębski, Maciej; Kobryń, Konrad; Grąt, Michał; Krawczyk, Marek

    2015-06-01

    Despite the aggressive nature and poor prognosis of gall-bladder cancer there is a group of patients who can achieve significant benefits from a radical surgical treatment. The possibility of obtaining long-term survival, even in case of patients with locally advanced cancer and metastases to regional lymph nodes, prompts to verify nihilistic approach to the treatment of this disease. Obviously such therapy can and should be performed only in centers specializing in hepatobiliary surgery. Due to the high recurrence rate, most of which are systemic, the hope of improving treatment outcomes should be sought in the use of combination therapy, based on a new chemotherapy and chemoradiotherapy regimens with the addition of targeted therapy. Unfortunately, the current application of these methods did not bring the expected benefits. PMID:26247506

  4. 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.

  5. 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

  6. 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

  7. 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

  8. New diagnostic and prognostic tools in bladder cancer.

    PubMed

    Tiguert, Rabi; Fradet, Yves

    2002-05-01

    Many efforts have been made to increase the detection rates and to predict the outcome of bladder cancer. Although to date cystoscopy remains the gold standard method for the detection of new or recurrent bladder cancer, its limitations were emphasized by the results of studies using fluorescence endoscopy that showed an increased detection rate and decreased recurrence after tumor resection. Urine cytology has high specificity and is used routinely as an adjunct to cystoscopy to detect invisible tumors. However, to improve on the low sensitivity of urine cytology, a number of marker tests have been developed. Optimal diagnostic accuracy appears to result from the synergistic combination of cytological markers with urine cytology. The evaluation of new and previously reported markers remains a very active field, but is still limited to inconclusive studies. Tissue and DNA microarrays represent a technological step forward for the analysis of a large number of markers and cohorts of patients that will be required definitively to establish the clinical utility of prognostic tests.

  9. Treatment of bladder cancer with Ho:YAG laser

    NASA Astrophysics Data System (ADS)

    Shi, Hong-Min; Zhu, Jing; Zhang, Hui-Guo; Zhang, Mei-Jue; Xu, Jian; Dai, Shen-guo; Wu, Jia-Jun; Jiang, Yu

    1998-11-01

    Among tumors of urinary system, the morbidity of bladder cancer is the first one. It is multiple, also has high risk of regeneration. The paper reports that 679 bladder tumors in 108 patients had treated for 284 times by pulsed HO:YAG laser from July 1994-June 1997.

  10. Incidental detection of increased (18)F-FDG uptake and its follow-up in patients with granulomatous prostatitis after BCG treatment for urinary bladder cancer.

    PubMed

    Kim, Choon-Young; Lee, Sang-Woo; Yoon, Ghilsuk; Jeong, Shin Young; Ahn, Byeong-Cheol; Lee, Jaetae

    2014-01-01

    Incidental prostate uptake of fluorine-18-fluorodeoxyglucose in positron emission tomography/computed tomography ((18)F-FDG PET/CT) may represent malignancies like prostate malignancy, inflammation or benign prostatic lesions. We report two cases of bacillus Calmette-Guérin (BCG)-induced granulomatous prostatitis that showed (18)F-FDG uptake of the prostate gland on (18)F-FDG PET/CT in patients who had previously received intravesical BCG treatment for bladder cancer. The degree of (18)F-FDG uptake was decreased on the follow-up PET/CT scan after one year, without any specific treatment.

  11. 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.

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

    PubMed

    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

    2016-03-29

    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. However, normal organs express and might also secrete AGR2, which would impact its utility as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is 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. Likewise, the blood proteomes of healthy people also contain no significant peptide counts for AGR2 suggesting little urothelial secretion into capillaries of the lamina propria. Expression of AGR2 is lost in urothelial carcinoma, with only 25% of primary tumors observed to retain 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 patients. The fraction of AGR2-positive urine samples was consistent with the fraction of urothelial carcinoma that stained positive for AGR2. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. Furthermore, AGR2 has also been found on the cell surface of cancer cells. Taken together, secretion and cell surface localization of AGR2 are characteristic of cancer, while expression of AGR2 by itself is not. PMID:26894971

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

    PubMed Central

    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.

    2016-01-01

    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. However, normal organs express and might also secrete AGR2, which would impact its utility as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is 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. Likewise, the blood proteomes of healthy people also contain no significant peptide counts for AGR2 suggesting little urothelial secretion into capillaries of the lamina propria. Expression of AGR2 is lost in urothelial carcinoma, with only 25% of primary tumors observed to retain 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 patients. The fraction of AGR2-positive urine samples was consistent with the fraction of urothelial carcinoma that stained positive for AGR2. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. Furthermore, AGR2 has also been found on the cell surface of cancer cells. Taken together, secretion and cell surface localization of AGR2 are characteristic of cancer, while expression of AGR2 by itself is not. PMID:26894971

  14. [New developments in the treatment of muscle-invasive bladder cancer].

    PubMed

    Kerst, J M; Pos, F J; Visser, O; Horenblas, S

    2008-01-26

    Muscle-invasive bladder cancer is an important oncological problem. When no distant metastases are detected, a radical cystectomy is the standard treatment. In recent years new developments in the treatment of the disease have been explored. These developments comprise new surgical techniques such as neobladder construction using the patient's intestinal tissue, sexuality-preserving surgery and robot-assisted surgery. Furthermore, indications for perioperative chemotherapy are discussed. Finally, bladder-sparing approaches are described: brachytherapy and chemo-radiation.

  15. 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

  16. Current animal models of bladder cancer: Awareness of translatability (Review)

    PubMed Central

    DING, JIE; XU, DING; PAN, CHUNWU; YE, MIN; KANG, JIAN; BAI, QIANG; QI, JUN

    2014-01-01

    Experimental animal models are crucial in the study of biological behavior and pathological development of cancer, and evaluation of the efficacy of novel therapeutic or preventive agents. A variety of animal models that recapitulate human urothelial cell carcinoma have thus far been established and described, while models generated by novel techniques are emerging. At present a number of reviews on animal models of bladder cancer comprise the introduction of one type of method, as opposed to commenting on and comparing all classifications, with the merits of a certain method being explicit but the shortcomings not fully clarified. Thus the aim of the present study was to provide a summary of the currently available animal models of bladder cancer including transplantable (which could be divided into xenogeneic or syngeneic, heterotopic or orthotopic), carcinogen-induced and genetically engineered models in order to introduce their materials and methods and compare their merits as well as focus on the weaknesses, difficulties in operation, associated problems and translational potential of the respective models. Findings of these models would provide information for authors and clinicians to select an appropriate model or to judge relevant preclinical study findings. Pertinent detection methods are therefore briefly introduced and compared. PMID:25120584

  17. Association between interleukin-22 genetic polymorphisms and bladder cancer risk

    PubMed Central

    Zhao, Tao; Wu, XiaoHou; Liu, JiaJi

    2015-01-01

    OBJECTIVE: The cytokine interleukin-22 (IL-22), which is produced by T cells and natural killer cells, is associated with tumorigenesis and tumor progression in cancers. However, the role of IL-22 in bladder cancer has not been investigated. MATERIALS AND METHODS: A prospective hospital-based case-control study comprising 210 patients with pathologically proven bladder cancer and 210 age- and gender-matched healthy controls was conducted. The genotypes of 3 common polymorphisms (-429 C/T, +1046 T/A and +1995 A/C) of the IL-22 gene were determined with fluorogenic 5' exonuclease assays. RESULTS: Patients with bladder cancer had a significantly higher frequency of the IL-22 -429 TT genotype [odds ratio (OR)=2.04, 95% confidence interval (CI)=1.19, 3.49; p=0.009] and -429 T allele (OR=1.42, 95% CI=1.08, 1.87; p=0.01) than the healthy controls. These findings were still significant after a Bonferroni correction. When stratifying according to the stage of bladder cancer, we found that patients with superficial bladder cancer had a significantly lower frequency of the IL-22 -429 TT genotype (OR=0.48, 95% CI=0.23, 0.98; p=0.04). When stratifying according to the grade and histological type of bladder cancer, we found no statistical association. The IL-22 +1046 T/A and IL-22 +1995 A/C gene polymorphisms were not associated with the risk of bladder cancer. CONCLUSION: To the authors' knowledge, this is the first report documenting that the IL-22 -429 C/T gene polymorphism is associated with bladder cancer risk. Additional studies are required to confirm this finding. PMID:26598081

  18. 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.

  19. 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

  20. 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

  1. Developing Urinary Metabolomic Signatures as Early Bladder Cancer Diagnostic Markers

    PubMed Central

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

    2015-01-01

    Abstract 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. PMID:25562196

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

    SciTech Connect

    Yee, Don; Parliament, Matthew; Rathee, Satyapal; Ghosh, Sunita; Ko, Lawrence; Murray, Brad

    2010-03-15

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

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

    PubMed

    Lin, Wei-Ching; Chen, Jeon-Hor

    2015-06-01

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

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

    PubMed

    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

  6. 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

  7. Update in Cancer Chemotherapy: Genitourinary Tract Cancer, Part 2: Wilms' Tumor and Bladder Cancer

    PubMed Central

    Wright, Jane C.

    1988-01-01

    An update of the state of the art of cancer chemotherapeutic treatment of genitourinary tract cancer is described in this multi-part series. Included in the review are cancers of the kidney, bladder, prostate, testicle, ovary, uterus, vulva, and gestational trophoblastic neoplasms. Part 2 focuses on Wilms' tumor and bladder cancer. Major advances have been made in the control of Wilms' tumor in children. The combination of surgery, chemotherapy, and radiotherapy have significantly improved survival rates. Likewise, the early diagnosis and control of bladder cancer has also improved survival. Surgery predominates among the treatment modalities for carcinoma of the bladder. Important progress is being made in the control of these conditions, as well as with other tumors of the genitourinary tract, with the use of cancer chemotherapy. PMID:2853770

  8. 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

  9. 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.

  10. CCDC34 is up-regulated in bladder cancer and regulates bladder cancer cell proliferation, apoptosis and migration

    PubMed Central

    Gong, Yanqing; Qiu, Wei; Ning, Xianghui; Yang, Xinyu; Liu, Libo; Wang, Zicheng; Lin, Jian; Li, Xuesong; Guo, Yinglu

    2015-01-01

    The coiled coil is a superhelical structural protein motif involved in a diverse array of biological functions, and the abnormal expression of the coiled-coil domain containing proteins has a direct link with the phenotype of tumor cell migration, invasion and metastasis. The aim of this study was to investigate the critical role of Coiled-coil domain-containing protein 34 (CCDC34) in bladder carcinogenesis, which has never been reported to date. Here, we found CCDC34 expression was elevated in bladder cancer tissues and cell lines. The knockdown of CCDC34 via lentivirus-mediated siRNA significantly suppressed bladder cancer cells proliferation and migration, and induced cell cycle arrest at G2/M phase and increased apoptosis in vitro. In addition, CCDC34 knockdown suppressed bladder tumor growth in nude mice. Moreover, CCDC34 silencing decreased the phosphorylation of MEK, ERK1/2, JNK, p38 and Akt, and the expressions of c-Raf and c-Jun, indicating MAPK and AKT pathways (ERK/MAPK, p38/MAPK, JNK/MAPK and PI3K/Akt) might be involved in CCDC34 regulation of bladder cancer cell proliferation and migration. Our findings revealed for the first time a potential oncogenic role for CCDC34 in bladder carcinoma pathogenesis and it may serve as a biomarker or even a therapeutic target for bladder cancer. PMID:26312564

  11. New therapeutical approaches for non muscle invasive bladder cancer.

    PubMed

    Volpe, Andrea; Racioppi, Marco; Sacco, Emilio; Bongiovanni, Luca; D'Agostino, Daniele; Cappa, Emanuele; Pinto, Francesco; Gardi, Mario; Totaro, Angelo; Bassi, PierFrancesco

    2008-12-01

    Non muscle invasive bladder cancer, given its high tendency to recur, coupled with an ever-present possibility to progress to potentially life-threatening muscle-invasive disease, remains a challenging clinical problem. Optimal management begins with early detection and accurate risk assessment through careful attention to clinical and histology features. Prevention of recurrence requires the sequential application of tools to completely remove all visible disease, avert reimplantation during surgical resection, ablate microscopic foci and prevent the emergence of new primary tumors amidst a field of carcinogen-exposed urothelium. Previously standard adjunctive intravesical chemo-immunotherapies are obtaining new vitality as optimization strategies, while new drugs and rational drug combinations provide the potential for improved efficacy with reduced toxicity. Novel therapeutic modalities under investigation include activation of the host immune system and enhancement of the cytotoxic effects of chemotherapeutic agents. New technological advances such as microwave chemothermotherapy offer further hope for better outcomes even for disease previously refractory to conservative measures. While much of this research is in the preclinical phase, the encouraging results of many of the studies discussed here suggest that testing in human trials should follow in the coming years. Yet despite these advances, aggressive surgical management involving bladder removal continues to be an indispensable life-saving maneuver that must be considered in all high-risk cases that fail to promptly respond to other measures. Although great strides continue to be made each year in the diagnosis and management of bladder cancer considerably more work needs to be done in order to improve the lives of our patients with this disease.

  12. 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

  13. 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. PMID:27080594

  14. 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.

  15. Androgen activates β-catenin signaling in bladder cancer cells.

    PubMed

    Li, Yi; Zheng, Yichun; Izumi, Koji; Ishiguro, Hitoshi; Ye, Bo; Li, Faqian; Miyamoto, Hiroshi

    2013-06-01

    Androgen receptor (AR) signals have been implicated in bladder carcinogenesis and tumor progression. Activation of Wnt/β-catenin signaling has also been reported to correlate with bladder cancer progression and poor patients' outcomes. However, cross talk between AR and β-catenin pathways in bladder cancer remains uncharacterized. In radical cystectomy specimens, we immunohistochemically confirmed aberrant expression of β-catenin especially in aggressive tumors. There was a strong association between nuclear expressions of AR and β-catenin in bladder tumors (P=0.0215). Kaplan-Meier and log-rank tests further revealed that reduced membranous β-catenin expression (P=0.0276), nuclear β-catenin expression (P=0.0802), and co-expression of nuclear AR and β-catenin (P=0.0043) correlated with tumor progression after cystectomy. We then assessed the effects of androgen on β-catenin in AR-positive and AR-negative bladder cancer cell lines. A synthetic androgen R1881 increased the expression of an active form of β-catenin and its downstream target c-myc only in AR-positive lines. R1881 also enhanced the activity of β-catenin-mediated transcription, which was abolished by an AR antagonist hydroxyflutamide. Using western blotting and immunofluorescence, R1881 was found to induce nuclear translocation of β-catenin when co-localized with AR. Finally, co-immunoprecipitation revealed androgen-induced associations of AR with β-catenin or T-cell factor (TCF) in bladder cancer cells. Thus, it was likely that androgen was able to activate β-catenin signaling through the AR pathway in bladder cancer cells. Our results also suggest that activation of β-catenin signaling possibly via formation of AR/β-catenin/TCF complex contributes to the progression of bladder cancer, which may enhance the feasibility of androgen deprivation as a potential therapeutic approach. PMID:23447569

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

    PubMed

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

    2016-05-01

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

  17. 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

  18. 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.

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

    PubMed

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

    2008-01-01

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

  20. 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.

  1. Treatment of bladder cancer in the elderly

    PubMed Central

    Erlich, Annette

    2016-01-01

    As the population ages and life expectancy increases in the human population, more individuals will be diagnosed with bladder cancer (BC). The definition of who is elderly is likely to change in the future from the commonly used cut-off of ≥75 years of age. Physiological rather than chronological age is key. BC care in the elderly is likely to become a very common problem in daily practice. Concerns have been raised that senior BC patients are not given treatments that could cure their disease. Clinicians lack quantitative and reliable estimates of competing mortality risks when considering treatments for BC. Majority of patients diagnosed with BC are elderly, making treatment decisions complex with their increasing number of comorbidities. A multidisciplinary approach to these patients may be a way to incorporate discussion from various disciplines regarding treatment options available. Here we review various treatment options for elderly patients with muscle invasive BC and nonmuscle invasive BC. We include differences in treatments from robotic versus open radical cystectomy, various urinary diversion techniques, chemotherapy, radiation therapy and combination treatments. In clinical practice, treatment decisions for elderly patients should be done on a case-by-case basis, tailored to each patient with their specific histories and comorbidities considered. Some healthy elderly patients may be better candidates for extensive curative treatments than their younger counterparts. This implies that these important, life-altering decisions cannot be solely based on age as many other factors can affect patient survival outcomes. PMID:27326404

  2. Treatment of bladder cancer in the elderly.

    PubMed

    Erlich, Annette; Zlotta, Alexandre R

    2016-06-01

    As the population ages and life expectancy increases in the human population, more individuals will be diagnosed with bladder cancer (BC). The definition of who is elderly is likely to change in the future from the commonly used cut-off of ≥75 years of age. Physiological rather than chronological age is key. BC care in the elderly is likely to become a very common problem in daily practice. Concerns have been raised that senior BC patients are not given treatments that could cure their disease. Clinicians lack quantitative and reliable estimates of competing mortality risks when considering treatments for BC. Majority of patients diagnosed with BC are elderly, making treatment decisions complex with their increasing number of comorbidities. A multidisciplinary approach to these patients may be a way to incorporate discussion from various disciplines regarding treatment options available. Here we review various treatment options for elderly patients with muscle invasive BC and nonmuscle invasive BC. We include differences in treatments from robotic versus open radical cystectomy, various urinary diversion techniques, chemotherapy, radiation therapy and combination treatments. In clinical practice, treatment decisions for elderly patients should be done on a case-by-case basis, tailored to each patient with their specific histories and comorbidities considered. Some healthy elderly patients may be better candidates for extensive curative treatments than their younger counterparts. This implies that these important, life-altering decisions cannot be solely based on age as many other factors can affect patient survival outcomes. PMID:27326404

  3. [THE SOMATIC MUTATIONS AND ABERRANT METHYLATION AS POTENTIAL GENETIC MARKERS OF URINARY BLADDER CANCER].

    PubMed

    Mikhailenko, D S; Kushlinskii, N E

    2016-02-01

    All around the world, more than 330 thousands cases of bladder cancer are registered annually hence representing actual problem of modern oncology. Still in demand are search and characteristic of new molecular markers of bladder cancer detecting in tumor cells from urinary sediment and having high diagnostic accuracy. The studies of last decade, especially using methods of genome-wide sequencing, permitted to receive a large amount of experimental data concerning development and progression of bladder cancer The review presents systematic analysis of publications available in PubMed data base mainly of last five years. The original studies of molecular genetic disorders under bladder cancer and meta-analyzes were considered This approach permitted to detected the most common local alterations of DNA under bladder cancer which can be detected using routine genetic methods indifferent clinical material and present prospective interest for development of test-systems. The molecular genetic markers of disease can be activating missense mutations in 7 and 10 exons of gene of receptor of growth factor of fibroblasts 3 (FGFR3), 9 and 20 exons of gene of Phosphatidylinositol-4,5-bi-phosphate-3-kinase (PIK3CA) and mutation in -124 and -146 nucleotides in promoter of gene of catalytic subunit telomerase (TERT). The development of test-systems on the basis of aberrant methylation of CpG-islets of genes-suppressors still is seemed as a difficult task because of differences in pattern of methylation of different primary tumors at various stages of clonal evolution of bladder cancer though they can be considered as potential markers.

  4. [THE SOMATIC MUTATIONS AND ABERRANT METHYLATION AS POTENTIAL GENETIC MARKERS OF URINARY BLADDER CANCER].

    PubMed

    Mikhailenko, D S; Kushlinskii, N E

    2016-02-01

    All around the world, more than 330 thousands cases of bladder cancer are registered annually hence representing actual problem of modern oncology. Still in demand are search and characteristic of new molecular markers of bladder cancer detecting in tumor cells from urinary sediment and having high diagnostic accuracy. The studies of last decade, especially using methods of genome-wide sequencing, permitted to receive a large amount of experimental data concerning development and progression of bladder cancer The review presents systematic analysis of publications available in PubMed data base mainly of last five years. The original studies of molecular genetic disorders under bladder cancer and meta-analyzes were considered This approach permitted to detected the most common local alterations of DNA under bladder cancer which can be detected using routine genetic methods indifferent clinical material and present prospective interest for development of test-systems. The molecular genetic markers of disease can be activating missense mutations in 7 and 10 exons of gene of receptor of growth factor of fibroblasts 3 (FGFR3), 9 and 20 exons of gene of Phosphatidylinositol-4,5-bi-phosphate-3-kinase (PIK3CA) and mutation in -124 and -146 nucleotides in promoter of gene of catalytic subunit telomerase (TERT). The development of test-systems on the basis of aberrant methylation of CpG-islets of genes-suppressors still is seemed as a difficult task because of differences in pattern of methylation of different primary tumors at various stages of clonal evolution of bladder cancer though they can be considered as potential markers. PMID:27455559

  5. 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.

  6. Glucocorticoid receptor beta increases migration of human bladder cancer cells.

    PubMed

    McBeth, Lucien; Nwaneri, Assumpta C; Grabnar, Maria; Demeter, Jonathan; Nestor-Kalinoski, Andrea; Hinds, Terry D

    2016-05-10

    Bladder cancer is observed worldwide having been associated with a host of environmental and lifestyle risk factors. Recent investigations on anti-inflammatory glucocorticoid signaling point to a pathway that may impact bladder cancer. Here we show an inverse effect on the glucocorticoid receptor (GR) isoform signaling that may lead to bladder cancer. We found similar GRα expression levels in the transitional uroepithelial cancer cell lines T24 and UMUC-3. However, the T24 cells showed a significant (p < 0.05) increased expression of GRβ compared to UMUC-3, which also correlated with higher migration rates. Knockdown of GRβ in the T24 cells resulted in a decreased migration rate. Mutational analysis of the 3' untranslated region (UTR) of human GRβ revealed that miR144 might positively regulate expression. Indeed, overexpression of miR144 increased GRβ by 3.8 fold. In addition, miR144 and GRβ were upregulated during migration. We used a peptide nucleic acid conjugated to a cell penetrating-peptide (Sweet-P) to block the binding site for miR144 in the 3'UTR of GRβ. Sweet-P effectively prevented miR144 actions and decreased GRβ expression, as well as the migration of the T24 human bladder cancer cells. Therefore, GRβ may have a significant role in bladder cancer, and possibly serve as a therapeutic target for the disease. PMID:27036026

  7. Nonsteroidal antiinflammatory drugs and bladder cancer: a pooled analysis.

    PubMed

    Daugherty, Sarah E; Pfeiffer, Ruth M; Sigurdson, Alice J; Hayes, Richard B; Leitzmann, Michael; Schatzkin, Arthur; Hollenbeck, Albert R; Silverman, Debra T

    2011-04-01

    Case-control studies have shown that regular use of nonsteroidal antiinflammatory drugs (NSAIDs) decreases bladder cancer risk, but few cohort studies have evaluated this association. The authors investigated NSAID use and bladder cancer in 3 large prospective studies (NIH-AARP Diet and Health Study; Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; and U.S. Radiologic Technologists Study). Frequency of aspirin and nonaspirin NSAID use 1 year prior to baseline was ascertained using self-administered questionnaires. Study-specific hazard ratios and 95% confidence intervals were estimated using Cox regression models and were combined using a fixed-effects meta-analytic model. Data from all studies were aggregated, and aggregated hazard ratios were estimated. The analysis included 508,842 individuals, with 2,489 incident cases of bladder cancer. A reduction in risk was observed for individuals who reported regular use (>2 times/week) of nonaspirin NSAIDs compared with those who reported no use (hazard ratio (HR) = 0.92, 95% confidence interval (CI): 0.81, 1.04). The risk reduction was limited to nonsmokers (HR = 0.58, 95% CI: 0.41, 0.83) (P(trend) = 0.008) (P(interaction) = 0.02). No association was observed between regular aspirin use and bladder cancer risk (HR = 1.04, 95% CI: 0.94, 1.15). Results suggest that nonaspirin NSAIDs, but not aspirin, are associated with a reduction in risk of bladder cancer, particularly for nonsmokers. PMID:21367875

  8. Glucocorticoid receptor beta increases migration of human bladder cancer cells

    PubMed Central

    McBeth, Lucien; Nwaneri, Assumpta C.; Grabnar, Maria; Demeter, Jonathan; Nestor-Kalinoski, Andrea; Hinds, Terry D.

    2016-01-01

    Bladder cancer is observed worldwide having been associated with a host of environmental and lifestyle risk factors. Recent investigations on anti-inflammatory glucocorticoid signaling point to a pathway that may impact bladder cancer. Here we show an inverse effect on the glucocorticoid receptor (GR) isoform signaling that may lead to bladder cancer. We found similar GRα expression levels in the transitional uroepithelial cancer cell lines T24 and UMUC-3. However, the T24 cells showed a significant (p < 0.05) increased expression of GRβ compared to UMUC-3, which also correlated with higher migration rates. Knockdown of GRβ in the T24 cells resulted in a decreased migration rate. Mutational analysis of the 3′ untranslated region (UTR) of human GRβ revealed that miR144 might positively regulate expression. Indeed, overexpression of miR144 increased GRβ by 3.8 fold. In addition, miR144 and GRβ were upregulated during migration. We used a peptide nucleic acid conjugated to a cell penetrating-peptide (Sweet-P) to block the binding site for miR144 in the 3′UTR of GRβ. Sweet-P effectively prevented miR144 actions and decreased GRβ expression, as well as the migration of the T24 human bladder cancer cells. Therefore, GRβ may have a significant role in bladder cancer, and possibly serve as a therapeutic target for the disease. PMID:27036026

  9. 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.

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

    PubMed Central

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

    2015-01-01

    Background: Controversy exists on whether urinary tract infection (UTI) is a risk factor for urinary bladder cancer (UBC). Here, the association is investigated using data from one of the largest bladder cancer case–control studies worldwide. Methods: Information on (i) history and age at onset of regular cystitis (‘regular low-UTI') and (ii) number and age at onset of UTI treated with antibiotics (‘UTI-ab') from 1809 UBC patients and 4370 controls was analysed. Odds ratios (ORs) and 95% confidence intervals (CI) adjusted for age, education, smoking, and use of aspirin/ibuprofen were generated, for men and women separately. Results: Regular low-UTI was associated with an increased UBC risk (men: OR (95% CI) 6.6 (4.2–11); women: 2.7 (2.0–3.5)), with stronger effects in muscle-invasive UBC. Statistically significant decreased risks (ORs ∼0.65) were observed for up to five UTI-ab, specifically in those who (had) smoked and experienced UTI-ab at a younger age. In women, UTI experienced after menopause was associated with a higher UBC risk, irrespective of the number of episodes. Conclusions: Regular cystitis is positively associated with UBC risk. In contrast, a limited number of episodes of UTI treated with antibiotics is associated with decreased UBC risk, but not in never-smokers and postmenopausal women. PMID:25429525

  11. 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

  12. 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.

  13. 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

  14. 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

  15. Cigarette smoking implicated in half of bladder cancers in women

    Cancer.gov

    Current cigarette smokers have a higher risk of bladder cancer than previously reported, and the risk in women is now comparable to that in men, according to a study by scientists from the National Cancer Institute (NCI), part of the National Institutes o

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

    PubMed

    Miyakawa, M; Yoshida, O

    1989-12-01

    Until the early 1970's there was little concern about dyes which contain benzidine as an integral part of their chemical structure. Furthermore, use of the finished dyes was not considered dangerous. To ascertain whether azo dyes are associated with risk of development of bladder tumors in workers who handpaint Yuzen-type silk kimonos in Kyoto, we investigated the disintegration of dyes to benzidine. In these studies, we found that in rats and mice benzidine-based dyes are metabolized to benzidine and that the azo linkage of benzidine dyes is reduced by Escherichia coli and soil bacteria. These experimental findings were reported previously. In this report, we outline an approach to these studies. Many of the dyes used to color paper, textiles, lipstick, bait used by fishermen, as well as hair dyes, and dyes used in research, for pharmaceutical products, and by defence personnel for the detection of liquid chemical warfare agents, have been shown to be potentially mutagenic or carcinogenic. We review the literature on these dyes. PMID:2618904

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

    PubMed

    Miyakawa, M; Yoshida, O

    1989-12-01

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

  18. Magnetic resonance imaging in the staging of bladder cancer.

    PubMed

    Persad, R; Kabala, J; Gillatt, D; Penry, B; Gingell, J C; Smith, P J

    1993-05-01

    Magnetic resonance imaging (MRI) scans were performed on 55 bladder cancer patients on whom clinicopathological staging was available from transurethral resection and cystectomy specimens. The overall accuracy of MRI scanning in this group was 84%, although true concordance rates are debatable without open surgical correlation. In the subgroup of 25 patients who had accurate open surgical correlation (from cystectomy, laparotomy or post mortem) the concordance rate was 76% with MRI. Errors occurred mainly in the T3 group of tumours, with 2 being overstaged and 2 being understaged out of a total of 12 in the open surgical correlation group (66% accuracy). Difficulties were also encountered in staging tumours at the bladder base, with an error rate of 22% (2 of 9) for T4 tumours in this area. With regard to lymph node staging there was a 100% (5 of 5) specificity in defining pathologically involved nodes but there was a false negative rate of 15% (3 of 19). Although it has many advantages over CT scanning, MRI produces a significant error rate in terms of over- and under-staging invasive tumours. There are difficulties associated with detecting minimal involvement of adjacent organs and lymph nodes as well as determining the exact depth of muscle penetration. Improvements may come in the future with the use of contrast enhancement agents such as gadolinium as well as more advanced machines.

  19. Advances in the management of superficial bladder cancer.

    PubMed

    O'Donnell, Michael A

    2007-04-01

    Given its high tendency to recur, coupled with an ever-present possibility to progress to potentially life-threatening muscle-invasive disease, superficial bladder cancer remains a challenging clinical problem. Optimal management begins with early detection and accurate risk assessment through careful attention to clinical features, aided by an emerging array of urinary markers and molecular characterizations. Prevention of recurrence requires the sequential application of tools to completely remove all visible disease, avert reimplantation during surgical resection, ablate microscopic foci, and prevent the emergence of new primary tumors amidst a field of carcinogen-exposed urothelium. Previously standard adjunctive intravesical chemo- and immunotherapies are enjoying new vitality as optimization strategies, new drugs, and rational drug combinations provide the potential for improved efficacy with reduced toxicity. New technological advances such as fluorescence-aided cystoscopy, microwave chemothermotherapy, and electromotive chemotherapeutic drug delivery offer further hope for better outcomes even for disease previously refractory to conservative measures. Yet despite these advances, aggressive surgical management involving bladder removal continues to be an indispensable life-saving maneuver that must be considered in all high-risk cases that fail to promptly respond to other measures.

  20. 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. PMID:27081483

  1. 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.

  2. Review of current optical diagnostic techniques for non-muscle-invasive bladder cancer

    PubMed Central

    Kołodziej, Anna; Matuszewski, Michał; Tupikowski, Krzysztof

    2016-01-01

    Introduction Urinary bladder urothelial cell carcinoma is one of the most commonly diagnosed cancers in Europe. After prostate, lung and colon cancers, bladder cancer rates as the fourth most common cancer in men in the world. Urinary bladder cancer detection, treatment, and staging have traditionally been based on an endoscopic examination – cystoscopy. Material and methods A Medline, and Web of Science database search was performed on September 2015 without setting time limits, using the terms ‘bladder cancer’ in conjunction with ‘cystoscopy’, ‘diagnosis’, ‘detection’, ‘fluorescence’, ‘blue-light’, ‘PDD’, ‘narrow band imaging’, ‘molecular imaging’, ‘optical coherence tomography’ or ‘confocal laser endomicroscopy’. Results The new imaging techniques can be classified according to their scope as macroscopic, microscopic, and molecular. Macroscopic techniques, such as narrow band imaging, are similar to white light cystoscopy; however, they help visualize even very minute lesions in the bladder mucosa by means of contrast enhancement. Microscopic imaging techniques, such as optical coherence tomography and confocal laser endomicroscopy, provide high-resolution cross-sectional views of vesicular tissues, which resemble images obtained by histopathological examination. Therefore, these are referred as ‘optical biopsy’. Molecular imaging methods offer highly specific real-time visualization of cancer cells and their differentiation from healthy tissue, by combining optical imaging with fluorescent labeling of elements such as antibodies. Conclusions In this article we present a review of studies and literature concerning modern optical diagnostic techniques for non-muscle-invasive bladder cancer. We present available technology with its advantages and disadvantages, and studies regarding its effectiveness. PMID:27551551

  3. Prevention of Urinary Bladder Cancer: The Interface Between Experimental and Human Studies.

    PubMed

    Fukushima, Shoji; Wanibuchi, Hideki

    2000-01-01

    1. Introduction: Bladder Cancer and the Environment Historical Aspects 2. Geographical Variation in Histopathological Types of Bladder Cancer Schistosomiasis Arsenic Poisoning Chernobyl 3. Analytical Epidemiological and Linked Experimental Findings Smoking Analgesic Abuse Saccharine 4. Histogenesis of Bladder Cancers Histopathology Molecular pathology 5. Carcinogens and Modification of Tumour Development Carcinogens Promoting agents Inhibitory agents 6. Prevention of Bladder Cancer Primary Prevention/ Lifestyle Factors/Chemoprevention Secondary Prevention/ Screening/Intervention Conclusions

  4. 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

  5. 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

  6. 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

  7. 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

  8. Bladder cancer: epidemiology and risk factors in Bulawayo, Zimbabwe.

    PubMed

    Vizcaino, A P; Parkin, D M; Boffetta, P; Skinner, M E

    1994-11-01

    The incidence of bladder cancer, and the importance of some selected risk factors in its etiology, were estimated from the data collected in the cancer registry of Bulawayo, Zimbabwe, during the period 1963-77. Cancer cases were interviewed with a standard questionnaire, and more than 70 percent of these were complete. Incidence rates in the urban population of Bulawayo in the first 10-year period were relatively high, with age standardized rates of 17.9 per 100,000 in men and 9.5 in women. Risk-factor distribution was compared in 680 bladder cancer cases (494 males, 186 females) and a control group comprising other cases with non-tobacco-related cancers (8,201). Seventy-one percent of bladder cancer cases were squamous cell carcinomas. The presence of schistosomiasis, evaluated from past history of bilharzia or hematuria, was associated with a significantly increased risk of bladder cancer in both genders (odds ratio [OR] = 3.9 for men, 5.7 for women), a result reflected in the differing risk by province of residence, which correlated with the prevalence of infection among cancer cases. The proportion of bladder cancer attributable to schistosomiasis was estimated to be 28 percent. Social status, as reflected by education level, also influenced risk (ORs for literate cf illiterate males = 0.6), but tobacco smoking in men had no effect on the risk of squamous cell tumors. For transitional cell carcinomas or adenocarcinomas, there was a nonsignificant increased risk of 2.0 in the highest smoking categories (15 g of tobacco per day), compared with non smokers.

  9. Preclinical Dosimetry of Magnetic Fluid Hyperthermia for Bladder Cancer

    PubMed Central

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

    2013-01-01

    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. PMID:23837123

  10. 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.

  11. 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.

  12. Prognostic Impact of Comorbidity in Patients with Bladder Cancer

    PubMed Central

    Megwalu, Ifeanyichukwu I.; Vlahiotis, Anna; Radwan, Mohamed; Piccirillo, Jay F.; Kibel, Adam S.

    2008-01-01

    Objective To determine the impact of comorbidity on survival of bladder cancer patients. Methods The population included 675 patients with newly diagnosed bladder cancer whose medical information was abstracted from a hospital cancer registry. Adult Comorbidity Evaluation-27, a validated instrument, was used to prospectively categorize comorbidity. Independent variables assessed include comorbidity, American Joint Committee on Cancer (AJCC) stage, grade, age, gender, and race. Outcome measure was overall survival. We analyzed the entire cohort, patients with noninvasive disease, and patients requiring cystectomy. Cox proportional hazards analysis was used to assess impact of independent variables on survival. Results Median age at diagnosis for the entire cohort was 71 yr and median follow-up was 45 mo. Of 675 patients, 446 had at least one comorbid condition and 301 died during follow-up. On multivariable analysis for the entire cohort, comorbidity (p = 0.0001), AJCC stage (p = 0.0001), age (p = 0.0001), and race (p = 0.0045) significantly predicted overall survival. On subset analysis of noninvasive bladder cancer patients, comorbidity (p = 0.0001) and age (p = 0.0001) independently predicted overall survival, whereas stage, grade, race, and gender did not. On subset analysis of cystectomy patients, comorbidity (p = 0.0053), stage (p = 0.0001), and race (p = 0.0449) significantly predicted overall survival. Conclusions Comorbidity is an independent predictor of overall survival in the entire cohort of bladder cancer patients, the subset with noninvasive disease, and the subset treated with cystectomy. PMID:17997024

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

    PubMed

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

    2016-02-01

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

  14. Nonmuscle invasive bladder cancer: a primer on immunotherapy.

    PubMed

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

    2016-06-01

    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

  15. 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

  16. 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! PMID:26225192

  17. [Epidemiological study of risk factors for bladder cancer].

    PubMed

    Nakata, S; Sato, J; Ohtake, N; Imai, K; Yamanaka, H

    1995-12-01

    A case-control study was conducted on 303 male bladder cancer patients and controls. General population controls were chosen from 15 areas in Gunma Prefecture and were matched by age (+/- l y.o.) to the subjects. Age-adjusted and smoking-adjusted odds ratio (O.R.) and a 95% confidence interval (C.I.) were calculated for each item. Risk factors for bladder cancer in men were investigated. The O.R. tended to be significantly higher for those who had history of smoking, who smoked more per day, who had smoked longer, whose Brinkman index was higher, who began smoking younger and who inhaled deeper than it was for non-smokers. O.R.s of having a past history or complication of cystitis (age-adjusted) and benign prostatic hypertrophy (age- and smoking-adjusted) were significantly higher, but the difference was supposed to be caused by bias. There was a significantly lower age- and smoking-adjusted O.R. for bladder cancer in men who engaged in sales, whose blood type was O, who drank milk frequently, who ate grains frequently, who age vegetables frequently and who had a past history or complication of hypertension. The number of cases and controls with first degree family members who developed cancer respectively supposed to be highly related to smoking, were as follows; 16 and 8 for lung cancer, 3 and 0 for larynx cancer and 6 and 3 for bladder cancer. The following characteristics failed to show any significant difference between subjects with bladder cancer and the control group; height and weight now and 20 years ago, jobs which deal with dye, academic career, marriage, number of children, alcohol drinking and the use of hair dye or analgesics. PMID:8578986

  18. The underactive bladder: detection and diagnosis

    PubMed Central

    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. PMID:27081483

  19. 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.

  20. 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.

  1. Valrubicin in refractory non-muscle invasive bladder cancer.

    PubMed

    Sharma, Pranav; Zargar-Shoshtari, Kamran; Sexton, Wade J

    2015-01-01

    The most effective intravesical regimen for the treatment of non-muscle invasive bladder cancer (NMIBC) refractory to Bacillus Calmette-Guérin (BCG) has still not been identified or optimized to minimize recurrence-free survival and prevent progression reliably and consistently. Valrubicin, however, is a cytotoxic chemotherapeutic agent that is used as an intravesical agent for BCG-refractory carcinoma in situ (CIS) of the urinary bladder in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality. Here we analyze the literature regarding the treatment of non-muscle invasive urothelial malignancies with intravesical valrubicin for refractory bladder cancer, present our opinion on its current clinical impact and speculate on how its utilization will evolve in the near future.

  2. Cruciferous vegetables, isothiocyanates, and prevention of bladder cancer

    PubMed Central

    Veeranki, Omkara L.; Bhattacharya, Arup; Tang, Li; Marshall, James R.; Zhang, Yuesheng

    2015-01-01

    Approximately 80% of human bladder cancers (BC) are non-muscle invasive when first diagnosed and are usually treated by transurethral tumor resection. But 50–80% of patients experience cancer recurrence. Agents for prevention of primary BC have yet to be identified. Existing prophylactics against BC recurrence, e.g., Bacillus Calmette-Guerin (BCG), have limited efficacy and utility; they engender significant side effects and require urethral catheterization. Many cruciferous vegetables, rich sources of isothiocyanates (ITCs), are commonly consumed by humans. Many ITCs possess promising chemopreventive activities against BC and its recurrence. Moreover, orally ingested ITCs are selectively delivered to bladder via urinary excretion. This review is focused on urinary delivery of ITCs to the bladder, their cellular uptake, their chemopreventive activities in preclinical and epidemiological studies that are particularly relevant to prevention of BC recurrence and progression, and their chemopreventive mechanisms in BC cells and tissues. PMID:26273545

  3. Selection of microsatellite markers for bladder cancer diagnosis without the need for corresponding blood.

    PubMed

    van Tilborg, Angela A G; Kompier, Lucie C; Lurkin, Irene; Poort, Ricardo; El Bouazzaoui, Samira; van der Keur, Kirstin; Zuiverloon, Tahlita; Dyrskjot, Lars; Orntoft, Torben F; Roobol, Monique J; Zwarthoff, Ellen C

    2012-01-01

    Microsatellite markers are used for loss-of-heterozygosity, allelic imbalance and clonality analyses in cancers. Usually, tumor DNA is compared to corresponding normal DNA. However, normal DNA is not always available and can display aberrant allele ratios due to copy number variations in the genome. Moreover, stutter peaks may complicate the analysis. To use microsatellite markers for diagnosis of recurrent bladder cancer, we aimed to select markers without stutter peaks and a constant ratio between alleles, thereby avoiding the need for a control DNA sample. We investigated 49 microsatellite markers with tri- and tetranucleotide repeats in regions commonly lost in bladder cancer. Based on analysis of 50 blood DNAs the 12 best performing markers were selected with few stutter peaks and a constant ratio between peaks heights. Per marker upper and lower cut off values for allele ratios were determined. LOH of the markers was observed in 59/104 tumor DNAs. We then determined the sensitivity of the marker panel for detection of recurrent bladder cancer by assaying 102 urine samples of these patients. Sensitivity was 63% when patients were stratified for LOH in their primary tumors. We demonstrate that up-front selection of microsatellite markers obliterates the need for a corresponding blood sample. For diagnosis of bladder cancer recurrences in urine this significantly reduces costs. Moreover, this approach facilitates retrospective analysis of archival tumor samples for allelic imbalance.

  4. Tumor motion and deformation during external radiotherapy of bladder cancer

    SciTech Connect

    Lotz, Heidi T.; Pos, Floris J.; Hulshof, Maarten C.C.M.; Herk, Marcel van; Lebesque, Joos V.; Duppen, Joop C.; Remeijer, Peter . E-mail: prem@nki.nl

    2006-04-01

    Purpose: First, to quantify bladder-tumor motion in 3 dimensions during a 4-week to 5-week course of external radiotherapy. Second, to relate the motion to the tumor location on the bladder wall. Third, to extensively evaluate gross tumor volume (GTV) shape and volume changes during the course of the treatment. Methods and Materials: Multiple repeat computed tomography (CT) images were obtained for 21 bladder cancer patients. These scans were matched to the rigid bony anatomy. For each patient, the main direction and magnitude of the tumor movement was determined by use of principle-component analysis. To study GTV shape changes, all GTVs were registered to the GTV in the planning CT scan, and the residual shape errors were determined by measurement of edge variations perpendicular to the median surface. Results: Gross tumor volume translations were largest in cranial-caudal and anterior-posterior direction (SD, 0.1 to {approx}0.9 cm). The translations were strongly correlated with the tumor location on the bladder wall. The average value of the local standard deviations of the GTV shape ranged from 0.1 to approximately 0.35 cm. Conclusions: Despite large differences in bladder filling, variations in GTV shape were small compared with variations in GTV position. Geometric uncertainties in the GTV position depended strongly on the tumor location on the bladder wall.

  5. 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

  6. Adaptive radiotherapy for invasive bladder cancer: A feasibility study

    SciTech Connect

    Pos, Floris J. . E-mail: f.pos@nki.nl; Hulshof, Maarten; Lebesque, Joos; Lotz, Heidi; Tienhoven, Geertjan van; Moonen, Luc; Remeijer, Peter

    2006-03-01

    Purpose: To evaluate the feasibility of adaptive radiotherapy (ART) in combination with a partial bladder irradiation. Methods and Materials: Twenty-one patients with solitary T1-T4 N0M0 bladder cancer were treated to the bladder tumor + 2 cm margin planning target volume (PTV{sub CONV}). During the first treatment week, five daily computed tomography (CT) scans were made immediately before or after treatment. In the second week, a volume was constructed encompassing the gross tumor volumes (GTVs) on the planning scan and the five CT scans (GTV{sub ART}). The GTV{sub ART} was expanded with a 1 cm margin for the construction of a PTV{sub ART}. Starting in the third week, patients were treated to PTV{sub ART}. Repeat CT scans were used to evaluate treatment accuracy. Results: On 5 of 91 repeat CT scans (5%), the GTV was not adequately covered by the PTV{sub ART}. On treatment planning, there was only one scan in which the GTV was not adequately covered by the 95% isodose. On average, the treatment volumes were reduced by 40% when comparing PTV{sub ART} with PTV{sub CONV} (p < 0.0001). Conclusion: The adaptive strategy for bladder cancer is an effective way to deal with treatment errors caused by variations in bladder tumor position and leads to a substantial reduction in treatment volumes.

  7. What Are the Risk Factors for Bladder Cancer?

    MedlinePlus

    ... of all bladder cancers in both men and women. If you or someone you know smokes and would like help quitting, see Guide to Quitting Smoking , or call us at 1-800-227-2345 for more information. Workplace exposures Certain industrial chemicals have been linked with ...

  8. BCG and the treatment of superficial bladder cancer.

    PubMed

    Moss, J T; Kadmon, D

    1991-12-01

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

  9. 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.

  10. A review on thiazolidinediones and bladder cancer in human studies.

    PubMed

    Tseng, Chin-Hsiao

    2014-01-01

    There is a concern of an increased risk of bladder cancer associated with the use of thiazolidinediones, a class of oral glucose-lowering drugs commonly used in patients with type 2 diabetes with a mechanism of improving insulin resistance. Human studies on related issues are reviewed, followed by a discussion on potential concerns on the causal inference in current studies. Pioglitazone and rosiglitazone are discussed separately, and findings from different geographical regions are presented. Randomized controlled trials designed for primarily answering such a cancer link are lacking, and evidence from clinical trials with available data for evaluating the association may not be informative. Observational studies have been reported with the use of population-based administrative databases, single-hospital records, drug adverse event reporting system, and case series collection. Meta-analysis has also been performed by six different groups of investigators. These studies showed a signal of higher risk of bladder cancer associated with pioglitazone, especially at a higher cumulative dose or after prolonged exposure; however, a weaker signal or null association is observed with rosiglitazone. In addition, there are some concerns on the causal inference, which may be related to the use of secondary databases, biases in sampling, differential detection, and confounding by indications. Lack of full control of smoking and potential biases related to study designs and statistical approaches such as prevalent user bias and immortal time bias may be major limitations in some studies. Overlapping populations and opposing conclusions in studies using the same databases may be of concern and weaken the reported conclusions of the studies. Because randomized controlled trials are expensive and unethical in providing an answer to this cancer issue, observational studies are expected to be the main source in providing an answer in the future. Furthermore, international comparison

  11. 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

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

    ClinicalTrials.gov

    2016-09-09

    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

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

    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) × 10-6 cm s-1 and (1.19 +/- 0.13) × 10-5 cm s-1 in normal and cancerous bladder tissues, respectively. The PCs of 50% DMSO are calculated to be (8.99 +/- 0.93) × 10-6 cm s-1 and (1.43 +/- 0.17) × 10-5 cm s-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.

  14. 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)

  15. 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

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

    PubMed

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

    1998-04-01

    The relationship between history of schistosomiasis and bladder cancer risk was investigated using data from a case-control study conducted between January 1994 and July 1996 in Alexandria, Egypt. Cases were 190 subjects with incident, histologically confirmed invasive cancer of the bladder, and controls were 187 subjects admitted to hospital for acute, non-neoplastic, non-urinary tract conditions. Eighty-six cases (45%) vs 69 controls (37%) reported a history of urinary schistosomiasis. The corresponding multivariate odds ratio (OR) of bladder cancer -- after allowance for age, sex, education, smoking, other urinary infections and high-risk occupations -- was 1.72 (95% confidence interval (CI) 1.0-2.9). The ORs were 0.22 (95% CI 0.1-0.4) for intestinal schistosomiasis and 0.32 (95% CI 0.1-1.9) for schistosomiasis of other types. The OR for urinary schistosomiasis was higher in subjects who were younger at first diagnosis (OR of 3.3 for <15 years) and in those with a long time since first diagnosis (OR of 3.0 for > or = 35 years). The ORs were 15.8 for male ever-smokers with a history of urinary schistosomiasis, compared with never-smokers without such a history, and 3.2 for men ever-infected with urinary Schistosoma haematobium and ever-employed in high-risk occupations, compared with those never-infected and with no high-risk occupational history. This study confirms that clinical history of urinary schistosomiasis is significantly, but modestly, associated with increased bladder cancer risk, explaining some 16% of bladder cancer cases in this Egyptian population.

  17. Tobacco use, occupation, coffee, various nutrients, and bladder cancer.

    PubMed

    Howe, G R; Burch, J D; Miller, A B; Cook, G M; Esteve, J; Morrison, B; Gordon, P; Chambers, L W; Fodor, G; Winsor, G M

    1980-04-01

    In a Canadian population-based case-control study of 480 males and 152 female case-control pairs, the relative risk for development of bladder cancer for ever used versus never used cigarettes was 3.9 for males and 2.4 for females, with a dose-response relationship in both sexes. A reduced risk was associated with the use of filter cigarettes compared to nonfilter cigarettes. After control for cigarette usage, a significant risk was noted for male pipe smokers. For male ex-smokers the risk after 15 years of no smoking was less than one-half that of current male smokers. Bladder cancer risk was found for workers in the chemical, rubber, photographic, petroleum, medical, and food processing industries among males and for workers occupationally exposed to dust or fumes among both sexes. Bladder cancer risk was elevated for males consuming all types of coffee, regular coffee, and instant coffee and for females consuming instant coffee, but no dose-response relationship was found. Risk was found for males consuming water from nonpublic supples but not for females. No risk was observed in males or females consuming nitrate-containing foods, beverages other than coffee, or fiddlehead greens. Hair dye usage in females and phenacetin usage in males and females carried no risk. Divergent findings by area for aspirin suggested that an overall association was not causal. Reevaluation of the data on artificial sweeteners confirmed a significant bladder cancer risk in males and a dose-response relationship. The cumulated population attributable risk for bladder cancer was 90% for males from cigarette smoking, industrial exposure, and exposure to nonpublic water supplies and 29% for females from cigarette smoking, industrial exposure, and instant coffee consumption.

  18. 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%.

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

    PubMed Central

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

    2015-01-01

    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. PMID:25947114

  20. 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.

  1. Potential Therapeutic Roles of Tanshinone IIA in Human Bladder Cancer Cells

    PubMed Central

    Chiu, Sheng-Chun; Huang, Sung-Ying; Chang, Shu-Fang; Chen, Shee-Ping; Chen, Chi-Cheng; Lin, Tien-Huang; Liu, Hsin-Ho; Tsai, Tsung-Hsun; Lee, Shang-Sen; Pang, Cheng-Yoong; Hsieh, Teng-Fu

    2014-01-01

    Tanshinone IIA (Tan-IIA), one of the major lipophilic components isolated from the root of Salviae Miltiorrhizae, has been found to exhibit anticancer activity in various cancer cells. We have demonstrated that Tan-IIA induces apoptosis in several human cancer cells through caspase- and mitochondria-dependent pathways. Here we explored the anticancer effect of Tan-IIA in human bladder cancer cell lines. Our results showed that Tan-IIA caused bladder cancer cell death in a time- and dose-dependent manner. Tan-IIA induced apoptosis through the mitochondria-dependent pathway in these bladder cancer cells. Tan-IIA also suppressed the migration of bladder cancer cells as revealed by the wound healing and transwell assays. Finally, combination therapy of Tan-IIA with a lower dose of cisplatin successfully killed bladder cancer cells, suggesting that Tan-IIA can serve as a potential anti-cancer agent in bladder cancer. PMID:25192287

  2. Adjuvant photodynamic therapy (PDT) of the superficial bladder cancer

    NASA Astrophysics Data System (ADS)

    Sokolov, V. V.; Russakov, I. G.; Teplov, A. A.; Filonenko, E. V.; Ul'yanov, R. V.; Bystrov, A. A.

    2005-08-01

    Superficial transitional cell carcinoma represents 50 to 80% of newly diagnosed bladder cancer in various countries. Transurethral resection of the urinary bladder is the standard procedure for biopsy and treatment superficial bladder cancer. However recurrence tumors after transurethral resection alone is high enough (50-90%). Intravesical chemotherapy for prophylaxis after complete transurethral resection is reducing recurrence rate about 1 5%. Adjuvant intravesical Bacillus of Calmette and Guerin (BCG) is reducing recurrence rate about 30%, but frequency side effects of this therapy is very high. Purpose of this study is appreciate efficacy adjuvant PDT with photosensitizer Photogeme (Russia) of superficial bladder cancer for prophylaxis after complete transurethral resection. The follow up was from 3 to 63 months (27 months, on average). Sixty-five patients (75.6%) showed no recurrence. For the follow up period, the recurrence was revealed in 21 (24.4%) patient, in two of them it was progressing (one case of invasive growth and one case of remote metastases). Four cases of recurrence were revealed 4 months after the surgery. In other cases, the recurrence was diagnosed from 9 to 18 months.

  3. 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

  4. 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.

  5. Outcome of urinary bladder cancer after combined therapies

    PubMed Central

    Anghel, RM; Gales, LN; Trifanescu, OG

    2016-01-01

    Rationale: Urinary bladder cancer is the fourth most common cancer in men and the eighth in women, being an important public health issue. Objective: to assess the outcome of patients with urinary bladder cancer treated in an oncologic center. Methods: Medical files of 155 patients (132M/ 23F) with urinary bladder cancer treated between 2006 and 2012 were retrospectively analyzed. The median age at diagnosis was 65 years (range: 19-85 years). Disease free survival (DFS) for patients with complete tumor resection receiving adjuvant treatment and progression free survival (PFS) for patients with post-operative residual disease was estimated. Results: Stage disease’s distribution was: 50 patients (32.2%) stage II, 47 (30.3%) stage III, 58 (37.4%) stage IV. Radical cystectomy was performed in 56 patients (36.1%), while 99 patients (63.9%) underwent repeated transurethral resection of the urinary bladder tumor (TURBT). The postoperative treatment included multimodal therapy in 47 patients (30.3%) (chemotherapy and external beam radiation), external beam radiation alone in 57 patients (36.8%) and chemotherapy alone (methotrexate, vinblastine, doxorubicin, and cisplatin-MVAC or gemcitabine + platinum) in 51 patients (32.9%). After a median follow-up of 31 months (range: 3-79 months), 51 patients (32.9%) presented local recurrence, 32 patients (21%) distant recurrence (metastases), 10 patients (6.4%) both local and distant recurrence, and 62 patients (40%) were free of disease. The median duration until progression was of 27 months. Discussion: Despite combined therapy approaches, urinary bladder carcinoma remains an aggressive disease, with high relapse rate. Earlier diagnosis and an aggressive radical surgery with the intention to cure (cystectomy), and adjuvant multimodal treatment (radiotherapy and chemotherapy) are needed for survival improvement. PMID:27453746

  6. 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

  7. An essential role for decorin in bladder cancer invasiveness

    PubMed Central

    El Behi, Mohamed; Krumeich, Sophie; Lodillinsky, Catalina; Kamoun, Aurélie; Tibaldi, Lorenzo; Sugano, Gaël; De Reynies, Aurélien; Chapeaublanc, Elodie; Laplanche, Agnès; Lebret, Thierry; Allory, Yves; Radvanyi, François; Lantz, Olivier; Eiján, Ana María; Bernard-Pierrot, Isabelle; Théry, Clotilde

    2013-01-01

    Muscle-invasive forms of urothelial carcinomas are responsible for most mortality in bladder cancer. Finding new treatments for invasive bladder tumours requires adequate animal models to decipher the mechanisms of progression, in particular the way tumours interact with their microenvironment. Herein, using the murine bladder tumour cell line MB49 and its more aggressive variant MB49-I, we demonstrate that the adaptive immune system efficiently limits progression of MB49, whereas MB49-I has lost tumour antigens and is insensitive to adaptive immune responses. Furthermore, we unravel a parallel mechanism developed by MB49-I to subvert its environment: de novo secretion of the proteoglycan decorin. We show that decorin overexpression in the MB49/MB49-I model is required for efficient progression, by promoting angiogenesis and tumour cell invasiveness. Finally, we show that these results are relevant to muscle-invasive human bladder carcinomas, which overexpress decorin together with angiogenesis- and adhesion/migration-related genes, and that decorin overexpression in the human bladder carcinoma cell line TCCSUP is required for efficient invasiveness in vitro. We thus propose decorin as a new therapeutic target for these aggressive tumours. PMID:24142880

  8. Assessing Symptom Burden in Bladder Cancer: An Overview of Bladder Cancer Specific Health-Related Quality of Life Instruments

    PubMed Central

    Danna, Bernard J.; Metcalfe, Michael J.; Wood, Erika L.; Shah, Jay B.

    2016-01-01

    Background: A key component to monitoring and investigating patient QOL is through patient reported health related quality of life (HRQOL) outcome measures. Many instruments have been used to assess HRQOL in bladder cancer and each instrument varies in its development, validation, the context of its usage in the literature and its applicability to certain disease states. Objective: In this review, we sought to summarize how clinicians and researchers should most appropriately utilize the available HRQOL instruments for bladder cancer. Methods: We performed a comprehensive literature search of each instrument used in bladder cancer, paying particular attention to the outcomes assessed. We used these outcomes to group the available instruments into categories best reflecting their optimal usage by stage of disease. Results: We found 5 instruments specific to bladder cancer, of which 3 are validated. Only one of the instruments (the EORTC-QLQ-NMIBC24) was involved in a randomized, prospective validation study. The most heavily used instruments are the EORTC-QLQ-BLM30 for muscle-invasive disease and the FACT-Bl which is used across all disease states. Of the 5 available instruments, 4 are automatically administered with general instruments, while the BCI lacks modularity, and requires co-administration with a generalized instrument. Conclusion: There are multiple strong instruments for use in gauging HRQOL in bladder cancer patients. We have divided these instruments into three categories which optimize their usage: instruments for use following NMIBC treatments (EORTC-QLQ-NMIBC24), instruments for use following radical cystectomy (FACT-Bl-Cys and EORTC-QLQ-BLM30) and more inclusive instruments not limited by treatment modality (BCI and FACT-Bl). PMID:27500200

  9. 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

  10. Bladder cancer: innovative approaches beyond the diagnosis.

    PubMed

    Piergentili, R; Carradori, S; Gulia, C; De Monte, C; Cristini, C; Grande, P; Santini, E; Gentile, V; Di Pierro, G B

    2014-01-01

    Bladder carcinoma (BC) is the most common urinary malignant tumor. In the light of the unsuccessful current therapies and their side effects, new pharmacological strategies are needed. In addition to the well known therapeutic possibilities described in the first section, we focused our attention on very recent and innovative tools to approach this target (new drug candidates from epigenetic modulators to endothelin receptor inhibitors, improved technological formulations, active principles from plants, and dietary components). Then, in the last paragraph, we analyzed the etiology of recurrent BC, with particular attention to cellular microenvironment. In fact, the incidence of recurrence is up to 90%, and 25% of tumours show progression towards invasiveness.

  11. 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

  12. G Protein-Coupled Receptor 87 (GPR87) Promotes Cell Proliferation in Human Bladder Cancer Cells.

    PubMed

    Zhang, Xia; Liu, Dage; Hayashida, Yushi; Okazoe, Homare; Hashimoto, Takeshi; Ueda, Nobufumi; Sugimoto, Mikio; Kakehi, Yoshiyuki

    2015-01-01

    G protein-coupled receptor 87 (GPR87) is a newly deorphanized member of the cell surface molecule G protein-coupled receptor family. GPR signaling was shown to play a role in promotion of cell growth and survival, metastasis, and drug resistance. The overexpression of GPR87 has also been reported in many malignant tumors including bladder cancer. The aim of the present study is to examine the effect of silencing GPR87 expression with a replication-deficient recombinant adenoviral vector expressing short hairpin RNA targeting GPR87 (Ad-shGPR87) and to explore the underlying molecular mechanisms in bladder cancer cells. Six GPR87-expressing human bladder cancer cells, HT1197, HT1376, J82, RT112, TCCSUP and UMUC3, were used. Infection with Ad-shGPR87 effectively downregulated the GPR87 expression, and significantly reduced the percentage of viable cells in 4 of 6 cell lines as detected by an MTT assay. Significant inhibition on cell proliferation with Ad-shGPR87 was observed in the wild-type p53 bladder cancer cell lines (HT1197, RT112, TCCSUP and UMUC3), but not in the mutant p53 cells (HT1376 and J82). As represented by a wild-type p53 RT112 cell, Ad-shGPR87 infection significantly enhanced p53 and p21 expression and caused caspase-dependent apoptosis. Furthermore, the treatment with Ad-shGPR87 exerted a significant antitumor effect against the GPR87-expressing RT112 xenografts. GPR87 appeared to be a promising target for gene therapy, and Ad-shGPR87 had strong antitumor effects, specifically anti-proliferative and pro-apoptotic effects, against GPR87-expressing human bladder cancer cells. PMID:26473854

  13. 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

  14. 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.

  15. 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.

  16. FAVL impairment of the Fanconi anemia pathway promotes the development of human bladder cancer

    PubMed Central

    Panneerselvam, Jayabal; Park, Hwan Ki; Zhang, Jun; Dudimah, Fred Duafalia; Zhang, Piyan; Wang, Hong; Fei, Peiwen

    2012-01-01

    Effectiveness of DNA cross-linking drugs in the treatment of bladder cancer suggests that bladder cancer cells may have harbored an insufficient cellular response to DNA cross-link damage, which will sensitize cells to DNA cross-linking agents. Cell sensitivity benefits from deficient DNA damage responses, which, on the other hand, can cause cancer. Many changed cellular signaling pathways are known to be involved in bladder tumorigenesis; however, DNA cross-link damage response pathway [Fanconi anemia (FA) pathway], whose alterations appear to be a plausible cause of the development of bladder cancer, remains an under-investigated area in bladder cancer research. In this study, we found FAVL (variant of FA protein L—FANCL) was elevated substantially in bladder cancer tissues examined. Ectopic expression of FAVL in bladder cancer cells as well as normal human cells confer an impaired FA pathway and hypersensitivity to Mitomycin C, similar to those found in FA cells, indicating that FAVL elevation may possess the same tumor promotion potential as an impaired FA pathway harbored in FA cells. Indeed, a higher level of FAVL expression can promote the growth of bladder cancer cells in vitro and in vivo, which, at least partly, results from FAVL perturbation of FANCL expression, an essential factor for the activation of the FA pathway. Moreover, a higher level of FAVL expression was found to be associated with chromosomal instability and the invasiveness of bladder cancer cells. Collectively, FAVL elevation can increase the tumorigenic potential of bladder cancer cells, including the invasive potential that confers the development of advanced bladder cancer. These results enhance our understanding the pathogenesis of human bladder cancer, holding a promise to develop additional effective tools to fight human bladder cancer. PMID:22828653

  17. Transurethral resection of the bladder tumour (TURBT) for non-muscle invasive bladder cancer: basic skills.

    PubMed

    Furuse, Hiroshi; Ozono, Seiichiro

    2010-08-01

    Transurethral resection of the bladder tumour (TURBT) is the standard surgical procedure for non-muscle invasive bladder cancer. We believe that all urologists should be trained in this procedure. This DVD provides an overview of TURBT with particular focus on basic skills, including basic surgical techniques such as the obturator nerve block. Important basic surgical skills required for complete TURBT in non-muscle invasive bladder cancer are: (i) resection of all visible tumors; (ii) resection of apparently normal mucosa on the border of the tumor; (iii) resection of the muscle layer at the base of the tumor until normal muscle fibers are visible; (iv) in applicable cases, random biopsy of apparently normal urothelium of the bladder wall and transurethral resection (TUR) biopsy of both sides of the prostatic urethra; and (v) when possible, after these procedures are completed, a different operating surgeon should inspect the bladder lumen to confirm that there are no remaining tumors. In particular, sampling resection should be implemented in apparently normal mucosa for approximately 1 cm around the tumor, and at the base of the tumor down to the superficial muscle layer. Resected specimens should be examined histopathologically in order to confirm the absence of malignant findings. Fundamental procedures for TURBT include both one-stage and two-stage resection. One-stage resection is used for relatively small tumors and involves a single procedure with simultaneous resection of both the tumor and the tissue at the tumor base down to the superficial muscle layer. In the two-stage resection, the first resection exposes the lower level of the mucosa and the second resection removes that lower mucosal layer in order to sample the superficial muscle layer for cancer staging. At the start of the resection, the loop is electrified before it makes contact with the mucosa. Delicate movements of the sheath should be used, along with delicate movement of the loop itself

  18. 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.

  19. 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. PMID:27221939

  20. 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

  1. 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.

  2. 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

  3. 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 Central

    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

    2011-01-01

    Objective 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. Design eCancerCareBladder and the EMR were used to retrieve data and produce clinical reports. Twelve participants (four attending staff, four fellows, and four residents) used either eCancerCareBladder or the EMR in two clinical scenarios simulating cystoscopy surveillance visits for bladder cancer follow-up. Measurements 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. Results eCancerCareBladder 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 eCancerCareBladder system (scenario 1: p<0.001; scenario 2: p=0.11). User satisfaction was higher with the eCancerCareBladder system, and 11/12 participants preferred to use this system. Limitations The small sample size affected the power of our study to detect differences. Conclusions 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. PMID:21816957

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    1981-02-15

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

  6. Bladder cancer and occupational exposure to polycyclic aromatic hydrocarbons.

    PubMed

    Bonassi, S; Merlo, F; Pearce, N; Puntoni, R

    1989-10-15

    The association between occupational exposure to polycyclic aromatic hydrocarbons (PAH) and bladder cancer development was investigated in a population-based case-control study carried out in the Bormida valley, Italy. One hundred and twenty-one male cases and 342 male controls, matched age, were collected from local hospitals. Occupational exposure to PAH and aromatic amines (AA) was evaluated by means of a job exposure matrix, constructed specifically for this study. Subjects considered as sharing a "definite exposure to PAH" showed an increased risk even after adjustment for cigarette smoking and exposure to AA (OR = 2.14, 95% CL 0.82-5.60). No elevation in risk was found for the category "possible exposure to PAH" (OR = 1.05, 95% CL 0.45-2.44). The findings of this study are consistent with previous studies indicating PAH as a risk factor for bladder cancer. A possible residual confounding effect due to AA impurities is discussed.

  7. 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

  8. [Descriptive epidemiologic study of 514 cases of bladder cancer].

    PubMed

    Calatayud Sarthou, A; Cortes Vizcaino, C; Talamante Serrula, S; Corella Piquer, D

    1994-01-01

    A descriptive epidemiological study was conducted on the characteristics and risk factors of 514 cases of bladder cancer. The results show a higher prevalence in males aged 70 or older. A higher incidence was found in those with a lower occupational level. There is a relationship with smoking and a Quetelet obesity score higher than normal. Anatomo-pathologically, the transitional cell type was the most common. A history of hematuria and obstructive disorders, basically arising from the prostate, were frequently found.

  9. 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.

  10. 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.

  11. Hexaminolevulinate-guided fluorescence cystoscopy reduces recurrence in patients with non-muscle invasive bladder cancer

    PubMed Central

    Stenzl, Arnulf; Burger, Maximilian; Fradet, Yves; Mynderse, Lance A.; Soloway, Mark S.; Witjes, J Alfred; Kriegmair, Martin; Karl, Alexander; Shen, Yu; Grossman, H Barton

    2015-01-01

    Purpose To assess the impact that improved detection of non-muscle invasive bladder cancer with hexaminolevulinate (HAL) fluorescence cystoscopy may have on early recurrence rates. Materials and methods This prospective, randomized study enrolled 814 patients suspected of having bladder cancer at increased risk for recurrence. All patients underwent white light cystoscopy and mapping of lesions, followed by transurethral resection of the bladder (TURB) where indicated. Patients in the fluorescence group also received intravesical hexaminolevulinate solution at least one hour before cystoscopy to induce fluorescence of cancerous lesions, and underwent additional inspection with blue light before and after TURB. Adjuvant intravesical therapy was based on risk. Follow up cystoscopies at 3, 6 and 9 months were conducted with white light. Results Detection was carried out as a within-patient comparison in the fluorescence group. In this group, 286 patients were found to have at least one Ta or T1 tumor (ITT). In 47 (16%), at least one of the tumors was seen only with fluorescence (p=0.001). During the 9 month follow-up period (ITT), there were tumor recurrences in 128/271 patients (47%) in the fluorescence group and 157/280 patients (56%) in the white light group (p=0.026). The relative reduction in recurrence rate was 16%. Conclusions HAL fluorescence cystoscopy significantly improves detection of Ta and T1 lesions and significantly reduces the rate of tumor recurrence at 9 months. PMID:20850152

  12. [Results of the multidisciplinary treatment of invasive bladder cancer].

    PubMed

    Miyakawa, M; Oishi, K; Okada, Y; Takeuchi, H; Okada, K; Yoshida, O

    1986-12-01

    Of the 843 patients with bladder cancer treated at Kyoto University between 1965 and 1984, 156 patients (18.6%) received total cystectomy. Between 1980 and 1984, 60 patients underwent multidisciplinary treatment with 4,000 or 2,400 rad adjuvant preoperative radiation therapy to the whole pelvis followed by radical cystectomy with or without postoperative adjuvant chemotherapy. The 5-year survival rate for the 65 patients with pelvic lymphadenectomy was 66% and that for the 40 patients without lymphadenectomy or only biopsy was 35%. The 5-year survival rate after radical cystectomy for 20 bladder cancer patients with regional lymph node metastasis was 11% and 73% for 59 patients without lymph node metastasis (p less than 0.001). The survival rate of multidisciplinary treatment protocol for muscle invasive bladder cancer was 55% a significantly (p less than 0.05) improved survival compared to the historical control. For analysis, the patients were divided into 2 categories according to histological criteria for evaluation of therapeutic effects for preoperative radiation by Ohoshi and Shimosato. The two groups were non-responder: grade I and IIa changes and responder: grade IIb, III and IV. Survival for responders and non-responders revealed significant differences (p less than 0.05), 87% for 28 responders and 48% for 24 non-responders.

  13. Diagnostic accuracy of cytokeratin-19 fragment (CYFRA 21-1) for bladder cancer: a systematic review and meta-analysis.

    PubMed

    Huang, Yuan-Lan; Chen, Jie; Yan, Wei; Zang, Ding; Qin, Qin; Deng, An-Mei

    2015-05-01

    Previous studies have evaluated the accuracy of serum and urinary measurements of cytokeratin-19 fragment (CYFRA 21-1) for the diagnosis of bladder cancer; however, the results have been inconsistent. The aim of this study was to evaluate the overall accuracy of CYFRA 21-1 for the diagnosis of bladder cancer. We performed a search for English-language publications reporting on the detection of CYFRA21-1 levels for the diagnosis of bladder cancer through November 2, 2014, using public medical databases, including EMBASE, Web of Science, and Medline. The quality of the studies was assessed by revised QUADAS tools. The performance characteristics were pooled and analyzed using a bivariate model. Publication bias was explored with the Deek's test. Sixteen studies, with a total 1,262 bladder-cancer patients and 1,233 non-bladder-cancer patients, were included in the study. The pooled sensitivities for serum and urine CYFRA 21-1 were 0.42 (95 % confidence interval (CI), 0.33-0.51) and 0.82 (95 % CI, 0.70-0.90), respectively. The corresponding specificities were 0.94 (95 % CI, 0.90-0.96) and 0.80 (95 % CI, 0.73-0.86), respectively. The areas under the summary receiver-operating-characteristic curves for serum and urine CYFRA 21-1 were 0.88 (95 % CI, 0.85-0.91) and 0.87 (95 % CI, 0.84-0.90), respectively. The major design deficiencies of the included studies were participant-selection bias, potential review, and verification bias. Therefore, we concluded that both serum and urine CYFRA 21-1 served as efficient indexes for bladder-cancer diagnosis. Additional, well-designed studies should be performed to rigorously evaluate the diagnostic value of CYFRA 21-1 for bladder cancer. PMID:25854170

  14. Bladder cancer in a young patient: Undiscovered risk factors

    PubMed Central

    KHAN, RAFAY; IBRAHIM, HIYAM; TULPULE, SUNIL; IROKA, NNEKA

    2016-01-01

    Bladder cancer is one of the most common forms of malignancies involving the urinary system and multiple risk factors have been associated with its etiology. The most common of which include cigarette smoking and various occupational or chemical exposures. It is usually diagnosed in older individuals with an average age of 70. In rare cases it is observed in children as well as young adults where it usually presents as a low-grade, non-invasive disease. In the present case report a 27-year-old male patient is discussed: The patient presented with no significant risk factors and was treated for mucinous adenocarcinoma of the bladder while further investigations were performed to identify other associated factors related to this form of malignancy. Debate in the literature exists in regards to the characteristics of bladder neoplasms in younger patients compared with older patients, however there is a lack of research into the etiology or prognosis in young patients. The present case study illustrates the case of a young adult with no clear risk factors who was diagnosed with a rare case of mucinous adenocarcinoma of the bladder. PMID:27123090

  15. 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.

  16. 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.

  17. 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

  18. [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.

  19. 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.

  20. 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

  1. TERT Core Promotor Mutations in Early-Onset Bladder Cancer.

    PubMed

    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

  2. TERT Core Promotor Mutations in Early-Onset Bladder Cancer.

    PubMed

    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.

  3. Screening for Bladder Cancer: Recommendations from the U.S.Preventive Services Task Force

    MedlinePlus

    ... known about it so far? In the United States, bladder cancer is the fourth and ninth most commonly diagnosed cancer in men and women, respectively. In 2009, about 70,000 new cases of bladder cancer were diagnosed in the United States and about 14,000 persons died of the ...

  4. 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

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

    PubMed

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

    2011-12-01

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

  6. Autophagy inhibition enhances RAD001-induced cytotoxicity in human bladder cancer cells

    PubMed Central

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

    2016-01-01

    Background Mammalian target of rapamycin (mTOR), involved in PI3K/AKT/mTOR pathway, is known to play a central role in regulating the growth of cancer cells. The PI3K/AKT/mTOR pathway enhances tumor survival and proliferation through suppressing autophagy, which sustains energy homeostasis by collecting and recycling cellular components under stress conditions. Conversely, inhibitors of the mTOR pathway such as RAD001 induce autophagy, leading to promotion of tumor survival and limited antitumor efficacy. We thus hypothesized that the use of autophagy inhibitor in combination with mTOR inhibition improves the cytotoxicity of mTOR inhibitors in bladder cancer. Materials and methods The cytotoxicity of RT4, 5637, HT1376, and T24 human bladder cancer cells treated with RAD001 alone or combined with autophagy inhibitors (3-methyladenine (3-MA), bafilomycin A1 (Baf A1), chloroquine, or hydroxychloroquine) was assessed using the WST-8 cell viability kit. The autophagy status in cells was analyzed by the detection of microtubule-associated light chain 3 form II (LC3-II), using immunofluorescent staining and Western blot. Acidic vesicular organelle (AVO) formation in treated cells was determined by acridine orange vital staining. Inhibition of mTOR pathway by RAD001 was monitored by using a homemade quantitative polymerase chain reaction gene array, while phospho-mTOR was detected using Western blot. Induced apoptosis was determined by measurement of caspase 3/7 activity and DNA fragmentation in cells after treatment. Results Advanced bladder cancer cells (5637, HT1376, and T24) were more resistant to RAD001 than RT4. Autophagy flux detected by the expression of LC3-II showed RAD001-induced autophagy. AVO formation was detected in cells treated with RAD001 and was inhibited by the addition of 3-MA or Baf A1. Cotreatment of RAD001 with autophagy inhibitors further reduced cell viability and induced apoptosis in bladder cancer cells. Conclusion Our results indicate that

  7. Perceptions of the causes of bladder cancer, nasal cancer, and mesothelioma among cases and population controls.

    PubMed

    Teschke, K; van Zwieten, L

    1999-12-01

    To understand the reasons for underreporting of occupational cancers, we investigated cases' perceptions of the causes of cancer. As part of a case-control study in the province of British Columbia, Canada, 105 bladder cancer cases, 48 nasal cancer cases, 51 mesothelioma cases, and 159 population-based controls (frequency matched to cases on age and sex) were interviewed using structured questions about their smoking, medical, residential, occupational, and carcinogen exposure histories. We asked cases what they thought caused their disease, and asked population controls about their understanding of the etiologies of the three cancers. Most cases and controls (69%) indicated that they had "no idea" about causes, with the exception that the majority of mesothelioma cases (70%) recognized asbestos as a cause. Smoking was perceived as a cause of bladder cancer by 21 percent of cases. Many cases knew about the asbestos and smoking etiologies from discussions with their physicians. Chemicals were commonly cited as causes of nasal and bladder cancer, but very few specific known or probable carcinogens for these sites were named. Cases (12%) more frequently than controls (2%) thought prior disease or trauma was a cause for all three types of cancer. Other etiologic factors less frequently listed by subjects included environmental pollution, hereditary factors, drugs, and radiation. Most cases recognized the major cause of mesothelioma, but few subjects knew about lifestyle or occupational causes of bladder cancer or nasal cancer, suggesting that education about the multiple cancer risks of smoking and about occupational carcinogens needs to be improved.

  8. Best practice in the treatment of nonmuscle invasive bladder cancer

    PubMed Central

    Anastasiadis, Anastasios

    2012-01-01

    Bladder carcinoma is the most common malignancy of the urinary tract. Approximately 75–85% of patients with bladder cancer present with a disease that is confined to the mucosa (stage Ta, carcinoma in situ) or submucosa (stage T1). These categories are grouped as nonmuscle invasive bladder cancer (NMIBC). Although the management of NMIBC tumours has significantly improved during the past few years, it remains difficult to predict the heterogeneous outcome of such tumours, especially if high-grade NMIBC is present. Transurethral resection is the initial treatment of choice for NMIBC. However, the high rates of recurrence and significant risk of progression in higher-grade tumours mandate additional therapy with intravesical agents. We discuss the role of various intravesical agents currently in use, including the immunomodulating agent bacillus Calmette-Guérin (BCG) and chemotherapeutic agents. We also discuss the current guidelines and the role of these therapeutic agents in the context of higher-grade Ta and T1 tumours. Beyond the epidemiology, this article focuses on the risk factors, classification and diagnosis, the prediction of recurrence and progression in NMIBC, and the treatments advocated for this invasive disease. PMID:22295042

  9. 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.

  10. Searching for urine biomarkers of bladder cancer recurrence using a liquid chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry metabolomics approach.

    PubMed

    Alberice, Juliana Vieira; Amaral, Andre F S; Armitage, Emily Grace; Lorente, José Antonio; Algaba, Ferrán; Carrilho, Emanuel; Márquez, Mirari; García, Antonia; Malats, Núria; Barbas, Coral

    2013-11-29

    The incidence and rate of recurrence of bladder cancer is high, particularly in developed countries, however current methods for diagnosis are limited to detecting high-grade tumours using often invasive methods. A panel of biomarkers to characterise tumours of different grades that could also distinguish between patients exhibiting the disease with first incidence or recurrence could be useful for bladder cancer diagnostics. In this study, potential metabolic biomarkers have been discovered through mass spectrometry based metabolomics of urine. Pre-treatment urine samples were collected from 48 patients diagnosed of urothelial bladder cancer. Patients were followed-up through the hospital pathological charts to identify whether and when the disease recurred or progressed. Subsequently, they were classified according to whether or not they suffered a tumour recurrence (recurrent or stable) as well as their risk group according to tumour grade and stage. Identified metabolites have been analysed in terms of disease characteristics (tumour stage and recurrence) and have provided an insight into bladder cancer progression. Using both liquid chromatography and capillary electrophoresis-mass spectrometry, a total of 27 metabolite features were highlighted as significantly different between patient groups. Some, for example histidine, phenylalanine, tyrosine and tryptophan have been previously linked with bladder cancer, however until now their connection with bladder cancer progression has not been previously reported. The candidate biomarkers revealed in this study could be useful in the clinic for diagnosis of bladder cancer and, through characterising the stage of the disease, could also be useful in prognostics.

  11. 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.

  12. 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

  13. Use of cone-beam computed tomography to characterize daily urinary bladder variations during fractionated radiotherapy for canine bladder cancer.

    PubMed

    Nieset, Jessica R; Harmon, Joseph F; Larue, Susan M

    2011-01-01

    Urinary bladder cancer is difficult to treat accurately with fractionated radiation therapy (RT) due to daily positional changes of the bladder and surrounding soft-tissue structures. We quantified the daily motion experienced by the canine bladder with patients in dorsal vs. sternal vs. lateral recumbency. We also described the dose distribution for three different planning target volume expansions (5, 10, and 15 mm) for each of the three positions to ensure adequate bladder dose and minimize irradiation of nearby healthy tissues. Analysis was based on data from retrospective daily cone-beam computed tomography (CT) (CBCT) images obtained for positioning of canine patients undergoing routine RT. Organs of interest were contoured on each CBCT data set and the images, along with the contours, were registered to the original planning CT. All measurements were made relative to the planning CT and dosimetric data for the organs of interest was determined using a dose volume histogram generated from sample parallel-opposed beam configuration. There was a wide range in bladder position throughout treatment. The least amount of bladder variation and the lowest rectal dose was with dogs in lateral recumbency. It was also determined that a margin of 10 mm would allow for sufficient dose to be delivered to the bladder while minimizing rectal dose.

  14. DIFFERENTIAL EXPRESSION OF STROMA DERIVED FACTOR-1 ISOFORMS IN BLADDER CANCER

    PubMed Central

    Yates, Travis J; Shields, John; Veerapen, Muthu K.; Merseburger, Axel S.; Rosser, Charles J; Soloway, Mark S.; Lokeshwar, Vinata B.

    2014-01-01

    Purpose Stroma-Derived Factor (SDF)-1 is a ligand for chemokine receptors CXCR4 and CXCR7. The six known SDF-1 isoforms are generated by alternative mRNA splicing. While SDF-1 expression has been detected in various malignancies, only a few studies have reported differential expression of SDF-1 isoforms and its clinical significance. In this study we evaluated the expression three SDF-1 isoforms (α,β,γ) in bladder cancer (BCa). Methods Using quantitative PCR, mRNA levels of SDF-1α, SDF-1β and SDF-1γ were measured in bladder tissues (normal: 25; BCa: 44) and urine specimens (n=210; normal: 28; benign conditions: 74; BCa: 57, history of BCa (HxBCa): 35, Hx other Ca: 8; other Ca: 8) from consecutive patients. These levels were correlated with clinical outcome. Results Among SDF-1 isoforms, only SDF-1β mRNA was significantly overexpressed by 2.5-6-fold in BCa tissues when compared to normal bladder tissues. While SDF-1α was expressed in bladder tissues, SDF-1γ expression was undetectable. In multivariate analysis, SDF-1β (P=0.017) was an independent predictor of metastasis and disease specific mortality (P=0.043). In exfoliated urothelial cells, only SDF-1β mRNA levels were differentially expressed and having a 91.2% sensitivity and 73.8% specificity for detecting BCa. In patients with HxBCa, elevated SDF-1β levels indicated 4.3-fold increased risk (P=0.0001) for developing recurrence within 6-months. Conclusion SDF-1 isoforms are differentially expressed in bladder tissues and exfoliated urothelial cells. SDF-1β mRNA levels in BCa tissues predict poor prognosis. Further, SDF-1β mRNA levels in exfoliated cells detect BCa with high sensitivity and are potential predictors of future recurrence. PMID:24291546

  15. Urinary Bladder Paraganglioma and Concomitant Metastatic Lung Cancer. A Case Report.

    PubMed

    Gkikas, Christos; Ram, Manisha; Tsafrakidis, Petros

    2016-03-01

    We present a case of an organ confined urinary bladder paraganglioma and concomitant metastatic lung cancer to the liver diagnosed on a 66 year old man initially though to be metastatic bladder cancer. The patient was referred to our hospital for frank hematuria and a single solid bladder tumor was identified at flexible cystoscopy. We are also reviewing the literature on the diagnostic and therapeutic approach of extra-adrenal phaeochromocytoma.

  16. Cystectomy and substitution enterocystoplasty: alternative primary treatment for T2/3 bladder cancer.

    PubMed

    Holmes, S A; Christmas, T J; Kirby, R S; Hendry, W F

    1992-03-01

    The optimal treatment for invasive bladder cancer remains controversial. Although external beam radiotherapy is able to eradicate the disease in a number of patients, the difficulty is selecting those who will respond. Those who do develop a local recurrence will require a salvage cystectomy combined with urinary diversion. The results of performing cystectomy and bladder reconstruction as a primary procedure are presented and the concept of combining this with chemotherapy as an alternative strategy for the management of bladder cancer is discussed.

  17. Bladder cancer survival in a former industrial area in Saxony-Anhalt, Germany.

    PubMed

    Roth, Emanuel; Selinski, Silvia; Schikowsky, Christian; Seidel, Thilo; Volkert, Frank; Blaszkewicz, Meinolf; Hengstler, Jan G; Golka, Klaus

    2012-01-01

    Long-term follow-ups on bladder cancer patients from highly industrialized areas are rare. Therefore, we present a follow-up of bladder cancer patients from the greater area Lutherstadt Wittenberg, a center of the chemical industry of the former German Democratic Republic. Relapse-free survival times of 213 confirmed bladder cancer cases from the greater area Lutherstadt Wittenberg were collected between 2008 and 2009. Data on lifestyle and occupational exposure to potential carcinogens was recorded by questionnaire. Genotypes of N-acetyltransferase 2 (NAT2), glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), rs710521, and rs9642880 were determined by standard methods. Cox models were used to evaluate differences in relapse-free survival. Clear differences in relapse-free survival could be observed for the number of relapses, multilocular tumor growth, and relapses with higher staging or grading than the primary tumor, as well as GSTT1. None of the other investigated polymorphisms showed significant impact on prognosis. This is the first study on two recently detected single-nucleotide polymorphisms (SNPs) showing that these polymorphisms may also contribute to shorter relapse-free times.

  18. 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

  19. Intravesical chemotherapy in non-muscle-invasive bladder cancer

    PubMed Central

    Porten, Sima P.; Leapman, Michael S.; Greene, Kirsten L.

    2015-01-01

    Non-muscle-invasive bladder cancer (NMIBC) is characterized by a tendency for recurrence and capacity for progression. Intravesical instillation therapy has been employed in various clinical settings, which are summarized within this review. Several chemotherapeutic agents have shown clinical efficacy in reducing recurrence rates in the post-transurethral resection of bladder tumor (TURBT) setting, including mitomycin C (MMC), doxorubicin, and epirubicin. Mounting evidence also supports the use of intravesical MMC following nephroureterectomy to reduce later urothelial bladder recurrence. In the adjuvant setting, bacillus Calmette-Guérin (BCG) immunotherapy is an established first-line agent in the management of carcinoma in situ (CIS) and high-grade non muscle invasive urothelial carcinoma (UC). Among high and intermediate-risk patients (based on tumor grade, size, and focality) improvements in disease-free intervals have been seen with adjunctive administration of MMC prior to scheduled BCG dosing. Following failure of first-line intravesical therapy, gemcitabine and valrubicin have demonstrated modest activity, though valrubicin remains the only agent currently Food and Drug Administration (FDA)-approved for the treatment of BCG-refractory CIS. Techniques to optimize intravesical chemotherapy delivery have also been explored including pharmacokinetic methods such as urinary alkalization and voluntary dehydration. Chemohyperthermia and electromotive instillation have been associated with improved freedom from recurrence intervals but may be associated with increased urinary toxicity. Improvements in therapeutic selection may be heralded by novel opportunities for genomic profiling and refinements in clinical risk stratification. PMID:26604440

  20. 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.

  1. 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...

  2. 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

  3. Rhenium-188 and copper-67 radiopharmaceuticals for the treatment of bladder cancer.

    PubMed

    Frier, Malcolm

    2004-01-01

    The favourable nuclear properties of copper-67 and rhenium-188 for therapeutic application are described, together with methods for the chemical synthesis of a number of derivatives. Survival from invasive bladder cancer has changed little over the past 20 years. The intravesicular administration of Cu-67 or Re-188 radiopharmaceuticals in the treatment of bladder cancer offers some promise for improvement in this situation.

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

    PubMed Central

    Zhao, Yang; Liu, Xiao-guang; Shi, Hao-qing; Hu, Ke-yao; Zhu, Guan-qun; Ma, Bo; Niu, Hai-tao

    2015-01-01

    A tumor microenvironment may promote tumor metastasis and progression through the dynamic interplay between neoplastic cells and stromal cells. In this work, the most representative and significant stromal cells, fibroblasts, endothelial cells, and macrophages were used as vital component elements and combined with bladder cancer cells to construct a bladder cancer microenvironment simulation system. This is the first report to explore bladder cancer microenvironments based on 4 types of 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. PMID:26462177

  5. Update on the management of invasive bladder cancer 2012

    PubMed Central

    Goethuys, Hans; Van Poppel, Hein

    2012-01-01

    Muscle-invasive bladder cancer is a deadly disease for which a number of new approaches have become available to improve prognosis. A recent review emphasized the importance of timely indication of surgery and highlighted current views regarding the adequate extent of the surgery and the importance of lymph node dissection. Furthermore, treatment using neoadjuvant and adjuvant systemic chemotherapy has become more prominent, while cystectomy and diversion should be conducted only in experienced centers. Optimal methods of urinary diversion and the use of robot-assisted laparoscopic cystectomy require further study. PMID:22904639

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

    PubMed Central

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

    2016-01-01

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

  7. Triple cancer: chronic lymphocytic leukemia with bladder and prostate carcinoma.

    PubMed

    Gajendra, Smeeta; Sharma, Rashi; Sahoo, Manas Kumar

    2015-08-01

    B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a common lymphoproliferative disorder with an increased risk of developing subsequent neoplasms of epithelial and mesenchymal origin. The decreased immunity and B-cell dysfunction in CLL probably accounts for this emergence of second malignancies. We report a case of synchronous bladder transitional cell carcinoma (TCC) and prostatic carcinoma with CLL. A 74-year-old male who underwent transurethral resection of the prostate (TURP) for benign prostatic hyperplasia 2 years before, presented with recurrent urinary tract infection. Peripheral blood smear revealed leukocytosis with absolute lymphocytosis (absolute lymphocyte count: 37870 cells/mm³). Flow cytometric immunophenotyping revealed 75% abnormal lymphoid cells which were positive for CD 19, CD5, CD23, CD22, CD200, CD20 (moderate) with lambda light chain restriction and negative for CD3, CD10, FMC7, CD38, CD138, IgM, CD103, CD123. F Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) showed increased metabolic activity of the left lateral wall of the urinary bladder extending to the left UV junction, adjacent part of trigone and bladder neck region along with multiple heterogeneous enhancing areas with increased FDG avidity within the prostate. Transurethral resection of the bladder tumour by cystoscopy was performed. Histopathology showed high grade, muscle invasive urothelial carcinoma. Due to presence of uptake in the prostate, transurethral resection of the prostate was done and histopathology revealed adenocarcinoma of prostate (prostate specific antigen- positive), Gleason grade III+III and Gleason score 6. A high index of suspicion is required to detect synchronous and metachronous malignancies. Ancillary studies such as immunohistochemistry, flow cytometry and PET/CT are often essential for detection and an accurate diagnosis.

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

    OK-432, a Streptococcus-derived anticancer immunotherapeutic agent, has been applied in clinic for many years and achieved great progress in various cancers. In the present study, we investigated its anticancer effect on bladder cancer through tumor associated macrophages (TAMs). MTS assay validated OK-432 could inhibit proliferation in both T24 and EJ bladder cell lines. OK-432 also induced apoptosis of bladder cancer cells in vitro. Consequently, we demonstrated that OK-432 could suppress the bladder cancer cells migration and invasion by altering the EMT-related factors. Furthermore, using SD rat model, we revealed that OK-432 inhibited tumor growth, suppressed PCNA expression and inhibited metastasis in vivo. Taken together, these findings strongly suggest that OK-432 inhibits cell proliferation and metastasis through inducing macrophages to secret cytokines in bladder cancer. PMID:26107200

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

    PubMed Central

    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.

    2016-01-01

    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. PMID:27376139

  11. Endoscopic Gold Fiducial Marker Placement into the Bladder Wall to Optimize Radiotherapy Targeting for Bladder-Preserving Management of Muscle-Invasive Bladder Cancer: Feasibility and Initial Outcomes

    PubMed Central

    Garcia, Maurice M.; Gottschalk, Alexander R.; Brajtbord, Jonathan; Konety, Badrinath R.; Meng, Maxwell V.; Roach, Mack; Carroll, Peter R.

    2014-01-01

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

  12. Image-guided radiation therapy for muscle-invasive bladder cancer.

    PubMed

    Thariat, Juliette; Aluwini, Shafak; Pan, Qiong; Caullery, Mickael; Marcy, Pierre-Yves; Housset, Martin; Lagrange, Jean-Leon

    2012-01-01

    Organ preservation protocols that incorporate chemoradiotherapy have shown good efficacy in bladder cancer. Owing to changes in rectal filling, urinary inflow and subsequent bladder volume with bladder wall deformations, irradiation must take into account interfractional and intrafractional internal target motion. Growing evidence suggests that image guidance during irradiation is essential in order to appropriately treat bladder cancer in this way. We performed a literature search on the imaging techniques and margins used for radiation therapy planning in the context of whole-bladder and partial-bladder irradiation. The most common image-guided radiation therapy (IGRT) method was based on cone-beam CT using anisotropic margins. The role of cine-MRI for the prediction of intraindividual bladder changes, in association with cone-beam CT or ultrasonography, is promising. Drinking protocols, diet and laxatives were used in most cases to minimize large variations in bladder size and shape. IGRT is crucial for avoiding tumor undercoverage and undue toxicity during radiation therapy for bladder cancer. IGRT-based adaptive radiation therapy can be performed using cone-beam CT or ultrasonography: modeling of bladder changes with cine-MRI or other imaging techniques might also be useful for facilitating adaptive radiation therapy with personalized margins.

  13. Long-term reduction in bladder cancer recurrence with hexaminolevulinate enabled fluorescence cystoscopy

    PubMed Central

    Grossman, H. Barton; Stenzl, Arnulf; Fradet, Yves; Mynderse, Lance A.; Kriegmair, Martin; Witjes, J. Alfred; Soloway, Mark S.; Karl, Alexander; Burger, Maximilian

    2012-01-01

    Purpose We assessed the impact that hexaminolevulinate fluorescence cystoscopic detection of papillary, non-muscle invasive bladder cancer has on long-term recurrence rates. Materials and Methods Long-term follow-up was assessed in 551 participants enrolled in a prospective, randomized study of fluorescence cystoscopy for Ta or T1 urothelial bladder cancer. In the original study, 280 patients in the white light cystoscopy group and 271 in the fluorescence cystoscopy group were followed with cystoscopy for 3, 6, and 9 months following the initial resection or until recurrence. A study extension protocol obtained long-term follow-up of these patients. Results Follow-up information was obtained for 261 of the 280 (93%) participants in the white light group and 255 of the 271 (94%) participants in the fluorescence group. Median follow-up in the white light and fluorescence groups were 53.0 and 55.1 months, respectively. In the white light and fluorescence groups, 83 (31.8%) and 97 (38%) of the participants remained tumor free, respectively. The median recurrence free survival was 9.6 months in the white light group and 16.4 months in the fluorescence group, p = 0.04. The rates of intravesical therapy were similar in the white light (46%) and fluorescence groups (45%). Cystectomy was performed in 22/280 (7.9%) in the white light group and 13/271 (4.8%) in the fluorescence group, p = 0.16. Conclusions Hexaminolevulinate fluorescence cystoscopy significantly improves long-term bladder cancer recurrence free survival with a trend towards improved bladder preservation. PMID:22583635

  14. The effect of vascular endothelial growth factor in the progression of bladder cancer and diabetic retinopathy

    PubMed Central

    Aldebasi, Yousef H; Rahmani, Arshad H; Khan, Amjad A; Aly, Salah Mesalhy

    2013-01-01

    Bladder cancer and diabetic retinopathy is a major public health and economical burden worldwide. Despite its high prevalence, the molecular mechanisms that induce or develop bladder carcinomas and diabetic retinopathy progression are poorly understood but it might be due to the disturbance in balance between angiogenic factors such as VEGF and antiangiogenic factors such as pigment epithelium derived growth factor. VEGF is one of the important survival factors for endothelial cells in the process of normal physiological and abnormal angiogenesis and induce the expression of antiapoptotic proteins in the endothelial cells. It is also the major initiator of angiogenesis in cancer and diabetic retinopathy, where it is up-regulated by oncogenic expression and different type of growth factors. The alteration in VEGF and VEGF receptors gene and overexpression, determines a diseases phenotype and ultimately the patient’s clinical outcome. However, expressional and molecular studies were made on VEGF to understand the exact mechanism of action in the genesis and progression of bladder carcinoma and diabetic retinopathy , but still how VEGF mechanism involve in such type of disease progression are not well defined. Some other factors also play a significant role in the process of activation of VEGF pathways. Therefore, further detailed analysis via molecular and therapeutic is needed to know the exact mechanisms of VEGF in the angiogenesis pathway. The detection of these types of diseases at an early stage, predict how it will behave and act in response to treatment through regulation of VEGF pathways. The present review aimed to summarize the mechanism of alteration of VEGF gene pathways, which play a vital role in the development and progression of bladder cancer and diabetic retinopathy. PMID:23641300

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

    PubMed

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

    2016-02-01

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

  16. Quantitative ultrasound imaging of therapy response in bladder cancer in vivo

    PubMed Central

    Tran, William T.; Sannachi, Lakshmanan; Papanicolau, Naum; Tadayyon, Hadi; Al Mahrouki, Azza; El Kaffas, Ahmed; Gorjizadeh, Alborz; Lee, Justin; Czarnota, Gregory J.

    2016-01-01

    Background and Aims Quantitative ultrasound (QUS) was investigated to monitor bladder cancer treatment response in vivo and to evaluate tumor cell death from combined treatments using ultrasound-stimulated microbubbles and radiation therapy. Methods Tumor-bearing mice (n=45), with bladder cancer xenografts (HT- 1376) were exposed to 9 treatment conditions consisting of variable concentrations of ultrasound-stimulated Definity microbubbles [nil, low (1%), high (3%)], combined with single fractionated doses of radiation (0 Gy, 2 Gy, 8 Gy). High frequency (25 MHz) ultrasound was used to collect the raw radiofrequency (RF) data of the backscatter signal from tumors prior to, and 24 hours after treatment in order to obtain QUS parameters. The calculated QUS spectral parameters included the mid-band fit (MBF), and 0-MHz intercept (SI) using a linear regression analysis of the normalized power spectrum. Results and Conclusions There were maximal increases in QUS parameters following treatments with high concentration microbubbles combined with 8 Gy radiation: (ΔMBF = +6.41 ± 1.40 (±SD) dBr and SI= + 7.01 ± 1.20 (±SD) dBr. Histological data revealed increased cell death, and a reduction in nuclear size with treatments, which was mirrored by changes in quantitative ultrasound parameters. QUS demonstrated markers to detect treatment effects in bladder tumors in vivo. PMID:27226985

  17. A departmental audit of patients with bladder cancer.

    PubMed Central

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

    1992-01-01

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

  18. Current trends in the management of invasive bladder cancer.

    PubMed

    Sibley, G N; Kabala, J

    1992-12-01

    In muscle-invasive bladder cancer, attempts at cure have traditionally involved radical local treatment by either radiotherapy or ablative surgery. However, these treatments have been associated with a high morbidity and have failed to address the problem of subsequent metastatic disease, to which many patients eventually succumb (often within the first 3 years after treatment). Modern imaging techniques have led to much improved staging information, allowing careful selection of patients suitable for radical "curative" treatment; at the same time, patients identified as already having metastatic disease may be spared major surgery that is unlikely to influence the outcome of their disease. Reconstructive surgical techniques are beginning to transform the quality of life for patients offered radical surgery, by avoiding the need for traditional urinary diversion. In addition, the use of neo-adjuvant chemotherapy combined with radical local treatment addresses the problem of micrometastases at diagnosis and offers the prospect of improved survival, although the results of clinical trials are awaited to evaluate this further. Future advances in treatment may be expected to occur as our understanding of the biology of bladder cancer increases. Of particular value will be predictive information about the invasive potential of initially superficial tumours, so that these cases may be targeted for "aggressive" treatment from the outset.

  19. Multiplatform Biomarker Discovery for Bladder Cancer Recurrence Diagnosis

    PubMed Central

    De Paoli, Marine; Gogalic, Selma; Sauer, Ursula; Preininger, Claudia; Pandha, Hardev; Simpson, Guy; Horvath, Andras

    2016-01-01

    Purpose. Nonmuscle invasive bladder cancer (BCa) has a high recurrence rate requiring lifelong surveillance. Urinary biomarkers are promising as simple alternatives to cystoscopy for the diagnosis of recurrent bladder cancer. However, no single marker can achieve the required accuracy. The purpose of this study was to select a multiparameter panel, comprising urinary biomarkers and clinical parameters, for BCa recurrence diagnosis. Experimental Design. Candidate biomarkers were measured in urine samples of BCa patients with recurrence and BCa patients without recurrence. A multiplatform strategy was used for marker quantification comprising a multiplexed microarray and an automated platform for ELISA analysis. A multivariate statistical analysis combined the results from both platforms with the collected clinical data. Results. The best performing combination of biomarkers and clinical parameters achieved an AUC value of 0.91, showing better performance than individual parameters. This panel comprises six biomarkers (cadherin-1, IL-8, ErbB2, IL-6, EN2, and VEGF-A) and three clinical parameters (number of past recurrences, number of BCG therapies, and stage at time of diagnosis). Conclusions. The multiparameter panel could be a useful noninvasive tool for BCa surveillance and potentially impact the clinical management of this disease. Validation of results in an independent cohort is warranted. PMID:27660385

  20. Multiplatform Biomarker Discovery for Bladder Cancer Recurrence Diagnosis

    PubMed Central

    De Paoli, Marine; Gogalic, Selma; Sauer, Ursula; Preininger, Claudia; Pandha, Hardev; Simpson, Guy; Horvath, Andras

    2016-01-01

    Purpose. Nonmuscle invasive bladder cancer (BCa) has a high recurrence rate requiring lifelong surveillance. Urinary biomarkers are promising as simple alternatives to cystoscopy for the diagnosis of recurrent bladder cancer. However, no single marker can achieve the required accuracy. The purpose of this study was to select a multiparameter panel, comprising urinary biomarkers and clinical parameters, for BCa recurrence diagnosis. Experimental Design. Candidate biomarkers were measured in urine samples of BCa patients with recurrence and BCa patients without recurrence. A multiplatform strategy was used for marker quantification comprising a multiplexed microarray and an automated platform for ELISA analysis. A multivariate statistical analysis combined the results from both platforms with the collected clinical data. Results. The best performing combination of biomarkers and clinical parameters achieved an AUC value of 0.91, showing better performance than individual parameters. This panel comprises six biomarkers (cadherin-1, IL-8, ErbB2, IL-6, EN2, and VEGF-A) and three clinical parameters (number of past recurrences, number of BCG therapies, and stage at time of diagnosis). Conclusions. The multiparameter panel could be a useful noninvasive tool for BCa surveillance and potentially impact the clinical management of this disease. Validation of results in an independent cohort is warranted.

  1. EZH2 in Bladder Cancer, a Promising Therapeutic Target

    PubMed Central

    Martínez-Fernández, Mónica; Rubio, Carolina; Segovia, Cristina; López-Calderón, Fernando F.; Dueñas, Marta; Paramio, Jesús M.

    2015-01-01

    Bladder Cancer (BC) represents a current clinical and social challenge. The recent studies aimed to describe the genomic landscape of BC have underscored the relevance of epigenetic alterations in the pathogenesis of these tumors. Among the epigenetic alterations, histone modifications occupied a central role not only in cancer, but also in normal organism homeostasis and development. EZH2 (Enhancer of Zeste Homolog 2) belongs to the Polycomb repressive complex 2 as its catalytic subunit, which through the trimethylation of H3 (Histone 3) on K27 (Lysine 27), produces gene silencing. EZH2 is frequently overexpressed in multiple tumor types, including BC, and plays multiple roles besides the well-recognized histone mark generation. In this review, we summarize the present knowledge on the oncogenic roles of EZH2 and its potential use as a therapeutic target, with special emphasis on BC pathogenesis and management. PMID:26580594

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

    PubMed Central

    Rubin, John R.; Hayward, Alexandra; Cates, Angelica L.; Day, Kathleen C.; El-Sawy, Layla; Kunju, L. Priya; Daignault, Stephanie; Lee, Cheryl T.; Liebert, Monica; Hussain, Maha; Day, Mark L.

    2016-01-01

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

  3. Cancer stem-like cells contribute to cisplatin resistance and progression in bladder cancer.

    PubMed

    Zhang, Yi; Wang, Zhi; Yu, Jin; Shi, Jia zhong; Wang, Chun; Fu, Wei hua; Chen, Zhi wen; Yang, Jin

    2012-09-01

    A variety of cancer stem-like cells (CSCs) have been shown to be responsible for cancer tumorigenicity, relapse and metastasis. Despite several reports demonstrating the presence of CSCs in human bladder cancer, their identities are still under debate, and few studies have examined their roles in cisplatin resistance and related tumor progression. In this study, a subpopulation of CSCs was enriched following cisplatin selection from the bladder cell line T24. The cisplatin-resistant T24 cells displayed a greater self-renewal capacity as demonstrated by higher levels of sphere formation and stem cell marker expression, contained a larger proportion of side population cells and exhibited higher tumorigenicity. They also possessed epithelial-mesenchymal transition characteristics. Furthermore, a strong correlation between the levels of Bmi1 and Nanog expression and the degree of malignancy of urothelial cell carcinomas tissues was observed. We provide the first direct evidence that CSC-like cells exist in the population of cisplatin-resistant bladder cancer cells and may play a role in the progression and drug resistance of bladder cancer. PMID:22343321

  4. Computer-aided detection of bladder mass within non-contrast-enhanced region of 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; Zhou, Chuan

    2016-03-01

    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 region of the bladder. In this study, we investigated methods for detection of bladder masses within the non-contrast enhanced region. The bladder was first segmented using a newly developed deep-learning convolutional neural network in combination with level sets. The non-contrast-enhanced region was separated from the contrast-enhanced region with a maximum-intensityprojection- based method. The non-contrast region was smoothed and a gray level threshold was employed to segment the bladder wall and potential masses. The bladder wall was transformed into a straightened thickness profile, which was analyzed to identify lesion candidates as a prescreening step. The lesion candidates were segmented using our autoinitialized cascaded level set (AI-CALS) segmentation method, and 27 morphological features were extracted for each candidate. Stepwise feature selection with simplex optimization and leave-one-case-out resampling were used for training and validation of a false positive (FP) classifier. In each leave-one-case-out cycle, features were selected from the training cases and a linear discriminant analysis (LDA) classifier was designed to merge the selected features into a single score for classification of the left-out test case. A data set of 33 cases with 42 biopsy-proven lesions in the noncontrast enhanced region was collected. During prescreening, the system obtained 83.3% sensitivity at an average of 2.4 FPs/case. After feature extraction and FP reduction by LDA, the system achieved 81.0% sensitivity at 2.0 FPs/case, and 73.8% sensitivity at 1.5 FPs/case.

  5. Non-muscle invasive bladder cancer risk stratification

    PubMed Central

    Isharwal, Sumit; Konety, Badrinath

    2015-01-01

    Introduction: Non-muscle invasive bladder cancer (NMIBC) comprises about 70% of all newly diagnosed bladder cancer, and includes tumors with stage Ta, T1 and carcinoma in situ (CIS.) Since, NMIBC patients with progression to muscle-invasive disease tend to have worse prognosis than with patients with primary muscle-invasive disease, there is a need to significantly improve risk stratification and earlier definitive treatment for high-risk NMIBC. Materials and Methods: A detailed Medline search was performed to identify all publications on the topic of prognostic factors and risk predictions for superficial bladder cancer/NMIBC. The manuscripts were reviewed to identify variables that could predict recurrence and progression. Results: The most important prognostic factor for progression is grade of tumor. T category, tumor size, number of tumors, concurrent CIS, intravesical therapy, response to bacillus Calmette–Guerin at 3- or 6-month follow-up, prior recurrence rate, age, gender, lymphovascular invasion and depth of lamina propria invasion are other important clinical and pathological parameters to predict recurrence and progression in patients with NMIBC. The European Organization for Research and Treatment of Cancer (EORTC) and the Spanish Club UrológicoEspañol de Tratamiento Oncológico (CUETO) risk tables are the two best-established predictive models for recurrence and progression risk calculation, although they tend to overestimate risk and have poor discrimination for prognostic outcomes in external validation. Molecular biomarkers such as Ki-67, FGFR3 and p53 appear to be promising in predicting recurrence and progression but need further validation prior to using them in clinical practice. Conclusion: EORTC and CUETO risk tables are the two best-established models to predict recurrence and progression in patients with NMIBC though they tend to overestimate risk and have poor discrimination for prognostic outcomes in external validation. Future

  6. Urinary bladder cancer in Wegener's granulomatosis: risks and relation to cyclophosphamide

    PubMed Central

    Knight, A; Askling, J; Granath, F; Sparen, P; Ekbom, A

    2004-01-01

    Objective: To assess and characterise the risk of bladder cancer, and its relation to cyclophosphamide, in patients with Wegener's granulomatosis. Methods: In the population based, nationwide Swedish Inpatient Register a cohort of 1065 patients with Wegener's granulomatosis, 1969–95, was identified. Through linkage with the Swedish Cancer Register, all subjects in this cohort diagnosed with bladder cancer were identified. Nested within the cohort, a matched case-control study was performed to estimate the association between cyclophosphamide and bladder cancer using odds ratios (ORs) as relative risk. In the cohort the cumulative risk of bladder cancer after Wegener's granulomatosis, and the relative prevalence of a history of bladder cancer at the time of diagnosis of Wegener's granulomatosis, were also estimated. Results: The median cumulative doses of cyclophosphamide among cases (n = 11) and controls (n = 25) were 113 g and 25 g, respectively. The risk of bladder cancer doubled for every 10 g increment in cyclophosphamide (OR = 2.0, 95% confidence interval (CI) 0.8 to 4.9). Treatment duration longer than 1 year was associated with an eightfold increased risk (OR = 7.7, 95% CI 0.9 to 69). The absolute risk for bladder cancer in the cohort reached 10% 16 years after diagnosis of Wegener's granulomatosis, and a history of bladder cancer was (non-significantly) twice as common as expected at the time of diagnosis of Wegener's granulomatosis. Conclusion: The results indicate a dose-response relationship between cyclophosphamide and the risk of bladder cancer, high cumulative risks in the entire cohort, and also the possibility of risk factors operating even before Wegener's granulomatosis. PMID:15130900

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

    PubMed

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

    2016-01-01

    Bladder cancer is among the five most common cancers diagnosed in the Western world and causes significant mortality and morbidity rates in affected patients. Therapeutic options to treat the disease in advanced muscle-invasive bladder cancer (MIBC) include cystectomy and chemotherapy. Neoadjuvant cisplatin-based combination chemotherapy is effective in MIBC; however, it has not been widely adopted by the community. One reason is that many patients do not respond to neoadjuvant chemotherapy, and no biomarker currently exists to identify these patients. It is also not clear whether a strategy to sensitize chemoresistant patients may exist. We sought to identify cisplatin-resistance patterns in preclinical models of bladder cancer, and test whether treatment with the epigenetic modifier decitabine is able to sensitize cisplatin-resistant bladder cancer cell lines. Using a screening approach in cisplatin-resistant bladder cancer cell lines, we identified dysregulated genes by RNA sequencing (RNAseq) and DNA methylation assays. DNA methylation analysis of tumors from 18 patients receiving cisplatin-based chemotherapy was used to confirm in vitro results. Cisplatin-resistant bladder cancer cells were treated with decitabine to investigate epigenetic sensitization of resistant cell lines. Our results show that HOXA9 promoter methylation status is associated with response to cisplatin-based chemotherapy in bladder cancer cell lines and in metastatic bladder cancer. Bladder cancer cells resistant to cisplatin chemotherapy can be sensitized to cisplatin by the DNA methylation inhibitor decitabine. Our data suggest that HOXA9 promoter methylation could serve as potential predictive biomarker and decitabine might sensitize resistant tumors in patients receiving cisplatin-based chemotherapy. PMID:27598218

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

    PubMed Central

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

    2016-01-01

    Bladder cancer is among the five most common cancers diagnosed in the Western world and causes significant mortality and morbidity rates in affected patients. Therapeutic options to treat the disease in advanced muscle-invasive bladder cancer (MIBC) include cystectomy and chemotherapy. Neoadjuvant cisplatin-based combination chemotherapy is effective in MIBC; however, it has not been widely adopted by the community. One reason is that many patients do not respond to neoadjuvant chemotherapy, and no biomarker currently exists to identify these patients. It is also not clear whether a strategy to sensitize chemoresistant patients may exist. We sought to identify cisplatin-resistance patterns in preclinical models of bladder cancer, and test whether treatment with the epigenetic modifier decitabine is able to sensitize cisplatin-resistant bladder cancer cell lines. Using a screening approach in cisplatin-resistant bladder cancer cell lines, we identified dysregulated genes by RNA sequencing (RNAseq) and DNA methylation assays. DNA methylation analysis of tumors from 18 patients receiving cisplatin-based chemotherapy was used to confirm in vitro results. Cisplatin-resistant bladder cancer cells were treated with decitabine to investigate epigenetic sensitization of resistant cell lines. Our results show that HOXA9 promoter methylation status is associated with response to cisplatin-based chemotherapy in bladder cancer cell lines and in metastatic bladder cancer. Bladder cancer cells resistant to cisplatin chemotherapy can be sensitized to cisplatin by the DNA methylation inhibitor decitabine. Our data suggest that HOXA9 promoter methylation could serve as potential predictive biomarker and decitabine might sensitize resistant tumors in patients receiving cisplatin-based chemotherapy. PMID:27598218

  9. Bladder Cancer 2000: Molecular Markers for the Diagnosis of Transitional Cell Carcinoma

    PubMed Central

    Chao, Debby; Freedland, Stephen J; Pantuck, Allan J; Zisman, Amnon; Belldegrun, Arie S

    2001-01-01

    The search continues for better tumor markers to improve the rate of detection of transitional cell carcinoma (TCC) more quickly in larger populations and to predict the possibility of disease recurrence. Among several new tests currently being screened, telomerase and hyaluronic acid/hyaluronidase (HA/HAase) have shown sensitivity and specificity equal to or better than cytology, and other promising tumor markers are being investigated. Although no marker has yet replaced the need to perform cystoscopy and cytology, the new tests can minimize the cost and difficulty of screening and long-term surveillance of patients who have or are at risk for bladder cancer. PMID:16985695

  10. Pursuing Quality in the Application of Bladder Cancer Quality of Life Research

    PubMed Central

    Mohamed, N.E.; Gilbert, F.; Lee, C.T.; Sfakianos, J.; Knauer, C.; Mehrazin, R.; Badr, H.; Wittmann, D.; Downs, T.; Berry, D.; Given, B.; Wiklund, P.; Steineck, G.

    2016-01-01

    Patient-reported outcomes (PRO), including health-related quality of life (HRQOL) measures, represent important means for evaluating patients’ health outcomes and for guiding health care decisions made by patients, practitioners, investigators, and policy makers. In spite of the large number of studies examining HRQOL in patients with bladder cancer, very few review articles investigated this topic. Because these review studies report mixed results, incorporating bladder cancer HRQOL measures into standard urological practice is not a viable option. In this non-systematic review of the literature and commentary we note some general concerns regarding PRO research, but our primary focus is on the HRQOL methodology within the context of two types of bladder cancer: muscle invasive and non-muscle invasive bladder cancer. Considering bladder cancer HRQOL as the interaction of four areas of the assessment process (i.e., what model of HRQOL to choose, what instruments are available to fit the choice, how interpretation of the resulting data fits the model, and how to derive some utility from the chosen model) and the two types of disease (i.e., muscle invasive and non-muscle invasive) may move us toward a better understanding of bladder cancer HRQOL. Establishing a useful model of perceived general health or specific symptoms is the first and most important step in developing the responsive bladder cancer HRQOL measures necessitated by clinical settings. PMID:27376136

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

    PubMed Central

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

    2016-01-01

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

  12. Presentation of case: Bladder cancer in an 18 year old female patient

    PubMed Central

    Sheehan, Lisa; Anwar, Adeel; Kommu, Sashi

    2014-01-01

    Introduction Bladder cancers are not very common in the young population below 20 years of age, especially in those who have not been exposed to chemotherapy, bladder augmentation surgery and other known risk factors. By highlighting this case we hope to raise awareness in the medical community, that the symptom of visible haematuria can potentially be due to a bladder malignancy and therefore this should be thoroughly investigated. Presentation of case An 18-year-old female presented with intermittent macroscopic haematuria and non-specific abdominal pain. Physical examination and routine blood tests were normal. An ultrasound scan initially showed a bladder wall lesion, which a flexible cystoscopy confirmed. Histology revealed grade 2 papillary transitional cell carcinoma of the bladder with no invasion into the lamina propria (G2pTa TCCB). Discussion We recognise through our literature review that paediatric bladder cancers are not commonly reported in the UK. In our paper we highlight the relevant major studies that have been carried out world-wide, the reported incidence so far and gaps in the evidence base. Conclusion Despite the dearth of data about paediatric bladder malignancies there is enough case-based evidence, from world-wide sources, to support that bladder cancer must be suspected in the event of macroscopic haematuria. Ultrasound and cystoscopy are the standard diagnostic tools for bladder tumours. Endoscopic resection of the tumour followed up by interval ultrasound scans and flexible cystoscopy checks remain the mainstay of treatment hitherto. PMID:25574770

  13. Ruthenium porphyrin-induced photodamage in bladder cancer cells.

    PubMed

    Bogoeva, Vanya; Siksjø, Monica; Sæterbø, Kristin G; Melø, Thor Bernt; Bjørkøy, Astrid; Lindgren, Mikael; Gederaas, Odrun A

    2016-06-01

    Photodynamic therapy (PDT) is a noninvasive treatment for solid malignant and flat tumors. Light activated sensitizers catalyze photochemical reactions that produce reactive oxygen species which can cause cancer cell death. In this work we investigated the photophysical properties of the photosensitizer ruthenium(II) porphyrin (RuP), along with its PDT efficiency onto rat bladder cancer cells (AY27). Optical spectroscopy verified that RuP is capable to activate singlet oxygen via blue and red absorption bands and inter system crossing (ISC) to the triplet state. In vitro experiments on AY27 indicated increased photo-toxicity of RuP (20μM, 18h incubation) after cell illumination (at 435nm), as a function of blue light exposure. Cell survival fraction was significantly reduced to 14% after illumination of 20μM RuP with 15.6J/cm(2), whereas the "dark toxicity" of 20μM RuP was 17%. Structural and morphological changes of cells were observed, due to RuP accumulation, as well as light-dependent cell death was recorded by confocal microscopy. Flow cytometry verified that PDT-RuP (50μM) triggered significant photo-induced cellular destruction with a photoxicity of (93%±0.9%). Interestingly, the present investigation of RuP-PDT showed that the dominating mode of cell death is necrosis. RuP "dark toxicity" compared to the conventional chemotherapeutic drug cisplatin was higher, both evaluated by the MTT assay (24h). In conclusion, the present investigation shows that RuP with or without photoactivation induces cell death of bladder cancer cells. PMID:26845686

  14. Semiautomatic bladder segmentation on CBCT using a population-based model for multiple-plan ART of bladder cancer

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

    selection between automatic bladder segmentation and manual delineation was 56.7%. The automatic segmentation and visual assessment took on average 7.8 and 9.7 s, respectively. In 53.4% of the cases, manual correction was performed after automatic segmentation. The manual correction improved the mean CI overlap, mean residual error and plan selection agreement to 77.7%, 0.30 cm and 80.7%, respectively. Manual correction required on average 8.4 markers and took on average 35.5 s. The statistical shape-based segmentation approach allows automatic segmentation of the bladder on CBCT with moderate accuracy. Limited user intervention can quickly and reliably improve the bladder contours. This segmentation method is suitable to select the appropriate plan for multiple-plan ART of bladder cancer.

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

    ClinicalTrials.gov

    2016-06-06

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

  16. Accurate Risk Assessment of Patients with Asymptomatic Hematuria for the Presence of Bladder Cancer

    PubMed Central

    Cha, Eugene K.; Tirsar, Lenuta-Ancuta; Schwentner, Christian; Hennenlotter, Joerg; Christos, Paul J.; Stenzl, Arnulf; Mian, Christine; Martini, Thomas; Pycha, Armin; Shariat, Shahrokh F.; Schmitz-Dräger, Bernd J.

    2014-01-01

    Purpose Bladder cancer is frequently diagnosed during a workup for hematuria. However, most patients with microscopic hematuria and many with gross hematuria are not appropriately referred to urologists. We hypothesized that in patients presenting with asymptomatic hematuria, the risk of having bladder cancer can be predicted with high accuracy. Towards this end, we analyzed risk factors in patients with asymptomatic hematuria and developed a nomogram for the prediction of bladder cancer presence. Methods Data from 1,182 consecutive subjects without a history of bladder cancer undergoing initial evaluation for asymptomatic hematuria were collected at three centers. Clinical risk factors including age, gender, smoking status, and degree of hematuria were recorded. All subjects underwent standard workup including voided cytology, upper tract imaging, and cystourethroscopy. Factors associated with the presence of bladder cancer were evaluated by univariable and multivariable logistic regression analyses. The multivariable analysis was used to construct a nomogram. Internal validation was performed using 200 bootstrap samples. Results Of the 1,182 subjects who presented with asymptomatic hematuria, 245 (20.7%) had bladder cancer. Increasing age (OR=1.03, p<0.0001), smoking history (OR=3.72, p<0.0001), gross hematuria (OR=1.71, p=0.002), and positive cytology (OR=14.71, p<0.0001) were independent predictors of bladder cancer presence. The multivariable model achieved 83.1% accuracy for predicting the presence of bladder cancer. Conclusions Bladder cancer presence can be predicted with high accuracy in patients who present with asymptomatic hematuria. We developed a nomogram to help optimize referral patterns (i.e., timing and prioritization) of patients with asymptomatic hematuria. PMID:23124847

  17. Bladder tumour antigen (BTA stat) test compared to the urine cytology in the diagnosis of bladder cancer: A meta-analysis

    PubMed Central

    Guo, Aiye; Wang, Xiuhua; Gao, Lan; Shi, Juan; Sun, Changyi; Wan, Zhen

    2014-01-01

    Introduction: We evaluate the diagnostic value of bladder tumour antigen (BTA stat) tests compared with urine cytology test in detecting bladder cancer. Methods: 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. Results: 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). Conclusions: 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. PMID:24940462

  18. Agricultural workers and urinary bladder cancer risk in Egypt.

    PubMed

    Amr, Sania; Dawson, Rebecca; Saleh, Doa'a A; Magder, Laurence S; Mikhail, Nabiel N; St George, Diane Marie; Squibb, Katherine; Khaled, Hussein; Loffredo, Christopher A

    2014-01-01

    The authors examined the associations between farming and the risk for squamous cell (SCC) or urothelial cell (UC) carcinoma of the urinary bladder among Egyptians. The authors used data from a multicenter case-control study (1,525 male and 315 female cases, and 2,069 male and 547 female age- and residence-matched, population-based controls) to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs). Men in farming and who never smoked had increased risk for either SCC or UC (AOR [95% CI]: 4.65 [2.59-8.36] and 6.22 [3.82-10.15], respectively). If they ever smoked, their risks were 2.27 (1.75-2.95) and 1.93 (1.58-2.35), respectively. Women in farmer households were at increased risk for SCC (1.40 [0.93-2.09] and UC [1.25 (0.82-1.89]), although not statistically significant. Occupational and environmental exposures to farming increased the risk for bladder cancer among Egyptians. PMID:23930791

  19. Galectin 3 for the diagnosis of bladder cancer

    PubMed Central

    El Gendy, Hoda; Madkour, Bothina; Abdelaty, Sara; Essawy, Fayza; Khattab, Dina; Hammam, Olfat; El Kholy, Amr; Nour, Hani H.

    2013-01-01

    Objective To evaluate serum levels of galectin-3 (G-3) in patients with bladder cancer and a control group, as a potential diagnostic and prognostic serum tumour marker. Patients and methods Between November 2012 and January 2013, 55 patients (median age 58 years) were enrolled into three groups, i.e., a control, those with transitional cell carcinoma (TCC) or those with squamous cell carcinoma (SCC). The serum G-3 level was measured the night before cystoscopy. The levels of G-3 levels were correlated with tumour type, stage and grade, and in relation to levels in normal urothelium. The results were analysed statistically using the Mann–Whitney U-test, the Kruskal–Wallis test and the receiver operating characteristic curve, as appropriate. Results The median serum G-3 level was 100, 720 and 920 pg/mL in the control, TCC and SCC groups, respectively, with very significantly greater G-3 levels in both the TCC and SCC groups than in the control group. Patients with high-grade TCC had a statistically significantly greater serum G-3 level than those with low-grade tumours, as did those with muscle-invasive TCC than those with Ta tumours. Conclusions The level of G-3 can aid as a diagnostic marker in patients with either TCC or SCC of the bladder, but the prognostic significance of G-3 remains to be confirmed. PMID:26019945

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

    PubMed Central

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

    2016-01-01

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

  1. Different effects of bladder distention on point A-based and 3D-conformal intracavitary brachytherapy planning for cervical cancer.

    PubMed

    Ju, Sang Gyu; Huh, Seung Jae; Shin, Jung Suk; Park, Won; Nam, Heerim; Bae, Sunhyun; Oh, Dongryul; Hong, Chae-Seon; Kim, Jin Sung; Han, Youngyih; Choi, Doo Ho

    2013-03-01

    This study sought to evaluate the differential effects of bladder distention on point A-based (AICBT) and three-dimensional conformal intracavitary brachytherapy (3D-ICBT) planning for cervical cancer. Two sets of CT scans were obtained for ten patients to evaluate the effect of bladder distention. After the first CT scan, with an empty bladder, a second set of CT scans was obtained with the bladder filled. The clinical target volume (CTV), bladder, rectum, and small bowel were delineated on each image set. The AICBT and 3D-ICBT plans were generated, and we compared the different planning techniques with respect to the dose characteristics of CTV and organs at risk. As a result of bladder distention, the mean dose (D50) was decreased significantly and geometrical variations were observed in the bladder and small bowel, with acceptable minor changes in the CTV and rectum. The average D2 cm(3)and D1 cm(3)showed a significant change in the bladder and small bowel with AICBT; however, no change was detected with the 3D-ICBT planning. No significant dose change in the CTV or rectum was observed with either the AICBT or the 3D-ICBT plan. The effect of bladder distention on dosimetrical change in 3D-ICBT planning appears to be minimal, in comparison with AICBT planning.

  2. Comparative Tissue Proteomics of Microdissected Specimens Reveals Novel Candidate Biomarkers of Bladder Cancer*

    PubMed Central

    Chen, Chien-Lun; Chung, Ting; Wu, Chih-Ching; Ng, Kwai-Fong; Yu, Jau-Song; Tsai, Cheng-Han; Chang, Yu-Sun; Liang, Ying; Tsui, Ke-Hung; Chen, Yi-Ting

    2015-01-01

    More than 380,000 new cases of bladder cancer are diagnosed worldwide, accounting for ∼150,200 deaths each year. To discover potential biomarkers of bladder cancer, we employed a strategy combining laser microdissection, isobaric tags for relative and absolute quantitation labeling, and liquid chromatography-tandem MS (LC-MS/MS) analysis to profile proteomic changes in fresh-frozen bladder tumor specimens. Cellular proteins from four pairs of surgically resected primary bladder cancer tumor and adjacent nontumorous tissue were extracted for use in two batches of isobaric tags for relative and absolute quantitation experiments, which identified a total of 3220 proteins. A DAVID (database for annotation, visualization and integrated discovery) analysis of dysregulated proteins revealed that the three top-ranking biological processes were extracellular matrix organization, extracellular structure organization, and oxidation-reduction. Biological processes including response to organic substances, response to metal ions, and response to inorganic substances were highlighted by up-expressed proteins in bladder cancer. Seven differentially expressed proteins were selected as potential bladder cancer biomarkers for further verification. Immunohistochemical analyses showed significantly elevated levels of three proteins—SLC3A2, STMN1, and TAGLN2—in tumor cells compared with noncancerous bladder epithelial cells, and suggested that TAGLN2 could be a useful tumor tissue marker for diagnosis (AUC = 0.999) and evaluating lymph node metastasis in bladder cancer patients. ELISA results revealed significantly increased urinary levels of both STMN1 and TAGLN2 in bladder cancer subgroups compared with control groups. In comparisons with age-matched hernia urine specimens, urinary TAGLN2 in bladder cancer samples showed the largest fold change (7.13-fold), with an area-under-the-curve value of 0.70 (p < 0.001, n = 205). Overall, TAGLN2 showed the most significant

  3. Oxidative stress induces hypomethylation of LINE-1 and hypermethylation of the RUNX3 promoter in a bladder cancer cell line.

    PubMed

    Wongpaiboonwattana, Wikrom; Tosukhowong, Piyaratana; Dissayabutra, Thasinas; Mutirangura, Apiwat; Boonla, Chanchai

    2013-01-01

    Increased oxidative stress and changes in DNA methylation are frequently detected in bladder cancer patients. We previously demonstrated a relationship between increased oxidative stress and hypomethylation of the transposable long-interspersed nuclear element-1 (LINE-1). Promoter hypermethylation of a tumor suppressor gene, runt-related transcription factor 3 (RUNX3), may also be associated with bladder cancer genesis. In this study, we investigated changes of DNA methylation in LINE-1 and RUNX3 promoter in a bladder cancer cell (UM-UC-3) under oxidative stress conditions, stimulated by challenge with H2O2 for 72 h. Cells were pretreated with an antioxidant, tocopheryl acetate for 1 h to attenuate oxidative stress. Methylation levels of LINE-1 and RUNX3 promoter were measured by combined bisulfite restriction analysis PCR and methylation-specific PCR, respectively. Levels of LINE-1 methylation were significantly decreased in H2O2-treated cells, and reestablished after pretreated with tocopheryl acetate. Methylation of RUNX3 promoter was significantly increased in cells exposed to H2O2. In tocopheryl acetate pretreated cells, it was markedly decreased. In conclusion, hypomethylation of LINE-1 and hypermethylation of RUNX3 promoter in bladder cancer cell line was experimentally induced by reactive oxygen species (ROS). The present findings support the hypothesis that oxidative stress promotes urothelial cell carcinogenesis through modulation of DNA methylation. Our data also imply that mechanistic pathways of ROS-induced alteration of DNA methylation in a repetitive DNA element and a gene promoter might differ.

  4. Comparison of adaptive radiotherapy techniques for external radiation therapy of canine bladder cancer.

    PubMed

    Nieset, Jessica R; Harmon, Joseph F; Johnson, Thomas E; Larue, Susan M

    2014-01-01

    Daily bladder variations make it difficult to utilize standard radiotherapy as a primary treatment option for muscle-invasive bladder cancer. Our purpose was to develop a model comparing dose distributions of image-guided and adaptive radiotherapy (ART) techniques for canine bladder cancer. Images were obtained retrospectively from cone-beam computed tomography (CBCT) scans used for daily positioning of four dogs undergoing fractionated image-guided radiotherapy (IGRT). Four different treatment plans were modeled for each dog, and dosimetric data were compared. Two plans were developed using planning target volumes based on planning computed tomography (CT) bladder volume. These plans then used bony anatomy or soft tissue anatomy for daily positioning and dosimetric modeling. The third plan type was a hybrid IGRT and ART technique utilizing a library of premade anisotropic planning target volumes using bladder wall motion data and selection of a "plan-of-the-day" determined from positioning CBCT bladder volumes. The fourth plan was an ART technique that constructed a new planning target volume each day based on daily bladder volume as determined by pretreatment CBCT. Dose volume histograms were generated for each plan type and dose distribution for the bladder and rectum were compared between plan types. Irradiated rectal volume decreased and irradiated bladder volume increased as plan conformality increased. ART provided the greatest rectal sparing, with lowest irradiated rectal volume (P < 0.001), and largest bladder volume receiving 95% of the prescription dose (P < 0.001). In our model, adaptive radiotherapy techniques for canine bladder cancer showed significant reduction in rectal volume irradiated when compared to nonadaptive techniques, while maintaining appropriate bladder coverage.

  5. Bladder Function Preservation With Brachytherapy, External Beam Radiation Therapy, and Limited Surger in Bladder Cancer Patients: Long-Term Results

    SciTech Connect

    Aluwini, Shafak; Rooij, Peter H.E. van; Kirkels, Wim J.; Boormans, Joost L.; Kolkman-Deurloo, Inger-Karina K.; Wijnmaalen, Arendjan

    2014-03-01

    Purpose: To report long-term results of a bladder preservation strategy for muscle-invasive bladder cancer (MIBC) using external beam radiation therapy and brachytherapy/interstitial radiation therapy (IRT). Methods and Materials: Between May 1989 and October 2011, 192 selected patients with MIBC were treated with a combined regimen of preoperative external beam radiation therapy and subsequent surgical exploration with or without partial cystectomy and insertion of source carrier tubes for afterloading IRT using low dose rate and pulsed dose rate. Data for oncologic and functional outcomes were prospectively collected. The primary endpoints were local recurrence-free survival (LRFS), bladder function preservation survival, and salvage cystectomy-free survival. The endpoints were constructed according to the Kaplan-Meier method. Results: The mean follow-up period was 105.5 months. The LRFS rate was 80% and 73% at 5 and 10 years, respectively. Salvage cystectomy-free survival at 5 and 10 years was 93% and 85%. The 5- and 10-year overall survival rates were 65% and 46%, whereas cancer-specific survival at 5 and 10 years was 75% and 67%. The distant metastases-free survival rate was 76% and 69% at 5 and 10 years. Multivariate analysis revealed no independent predictors of LRFS. Radiation Therapy Oncology Group grade ≥3 late bladder and rectum toxicity were recorded in 11 patients (5.7%) and 2 patients (1%), respectively. Conclusions: A multimodality bladder-sparing regimen using IRT offers excellent long-term oncologic outcome in selected patients with MIBC. The late toxicity rate is low, and the majority of patients preserve their functional bladder.

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

    SciTech Connect

    Turgeon, Guy-Anne; Souhami, Luis; Cury, Fabio L.; Faria, Sergio L.; Duclos, Marie; Sturgeon, Jeremy; Kassouf, Wassim

    2014-02-01

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

  7. Monitoring of the upper urinary tract in patients with bladder cancer

    PubMed Central

    Ayyathurai, Rajinikanth; Soloway, Mark S.

    2011-01-01

    Upper urinary tract (UUT) transitional cell carcinoma (TCC) is relatively rare tumor. Approximately 0.7-4% of patients with primary bladder cancer develops UUT-TCC. The symptoms related to an UUT-TCC often occur with an advanced stage which leads one to emphasize a surveillance strategy to monitor the UUT to allow for an earlier diagnosis. Although the risk of UUT-TCC after bladder cancer is well established, there is a paucity of recommendations suggesting the optimal method and frequency of monitoring the UUT and there is no consensus among them. This article reviews the recommendations on monitoring the UUT in patients with bladder cancer. PMID:21814316

  8. Rare but Lethal Disease of Childhood: Metastatic, Muscle Invasive Bladder Cancer

    PubMed Central

    Aykan, Serdar; Yuruk, Emrah; Tuken, Murat; Temiz, Mustafa Zafer; Ozsoy, Sule

    2015-01-01

    Bladder cancer is the most common malignancy of urinary tract and the seventh most common cancer in men with the peak incidence in the sixth decade of life. Our knowledge about bladder tumors in pediatric age group mainly relies on case series. The reported cases are mostly low grade and non-muscle invasive. We herein present a case of a 17-year-old male with metastatic high-grade muscle-invasive bladder cancer who was presented with macroscopic hematuria and flank pain. PMID:26500746

  9. Bladder cancer risk from the perspective of genetic polymorphisms in the carcinogen metabolizing enzymes.

    PubMed

    Antonova, Olga; Toncheva, Draga; Grigorov, Evgeni

    2015-01-01

    Urinary bladder cancer is a socially significant healthcare problem. A diverse array of aromatic and heterocyclic amines, derived from the chemical and transport industry, diet, and cigarette smoke are considered carcinogens for the bladder. To exert their carcinogenic effect and to initiate the carcinogenic response, the arylamines require a metabolic activation by the host enzymes to chemically reactive compounds. The aim of this article was to review the latest and basic research developments on the role of the polymorphisms in the carcinogen metabolizing enzymes N-acetyltransferase (NAT), Glutathione S-transferases (GST), and Soluble sulfotransferases (SULT), with emphasis on the susceptibility to urinary bladder cancer. A PubMed search was conducted to identify original and review articles containing information about these polymophic variants in different populations and according to their prevalence in bladder cancer patients. We noticed that some genotypes were found to be predisposing and some protective for bladder cancer development. The NAT2 slow genotype, together with GSTM1 null genotype facilitated the development of bladder cancer in almost all ethnic groups. The 213His allele of the SULT1A1 gene which is associated with lower enzyme activity and decreased mutagen activation was reported to protect from bladder cancer in almost all studies. PMID:26854433

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

    PubMed

    Yeung, Christina; Dinh, Tuan; Lee, Joseph

    2014-11-01

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

  11. Recombinant Mycobacterium bovis BCG for immunotherapy in nonmuscle invasive bladder cancer.

    PubMed

    Begnini, K R; Buss, J H; Collares, T; Seixas, F K

    2015-05-01

    In the past three decades, intravesical instillation of Mycobacterium bovis bacille Calmette-Guérin (BCG) has been used for treating bladder cancer and it still remains at the forefront of immunotherapy for cancer patients. Although BCG-based therapy is the most effective intravesical therapy for this kind of tumor and represents the only agent known to reduce progression into muscle invasive bladder cancer, BCG is ineffective in approximately 30-40 % of cases and disease recurs in up to 50 % of patients. Since that BCG is considered an effective vehicle for delivery of antigens due to its unique characteristics, the genetic manipulation of these mycobacteria has been appealing in the search for less toxic and more potent therapeutic agents for bladder cancer immunotherapy. Herein, we discuss current advances in recombinant BCG construction, research, concerns, and future directions to promote the development of this promising immunotherapeutic approach for bladder cancer.

  12. Increasing Age and Treatment Modality Are Predictors for Subsequent Diagnosis of Bladder Cancer Following Prostate Cancer Diagnosis

    SciTech Connect

    Singh, Anurag K.; Mashtare, Terry L.; McCloskey, Susan A.; Seixas-Mikelus, Stefanie A.; Kim, Hyung L.; May, Kilian Salerno

    2010-11-15

    Purpose: To determine the effect of prostate cancer therapy (surgery or external beam irradiation, or both or none) on the actuarial incidence of subsequent bladder cancer. Methods and Materials: The Surveillance, Epidemiology, and End Results registry from 1973 to 2005 was analyzed. Treatment was stratified as radiotherapy, surgery, both surgery and adjuvant radiation, and neither modality. Brachytherapy was excluded. Results: In all, 555,337 prostate carcinoma patients were identified; 124,141 patients were irradiated; 235,341 patients were treated surgically; 32,744 patients had both surgery and radiation; and 163,111 patients received neither modality. Bladder cancers were diagnosed in: 1,836 (1.48%) men who were irradiated (mean age, 69.4 years), 2,753 (1.09%) men who were treated surgically (mean age, 66.9 years); 683 (2.09%) men who received both modalities (mean age, 67.4 years), and 1,603 (0.98%) men who were treated with neither modality (mean age, 71.8 years). In each treatment cohort, Kaplan-Meier analyses showed that increasing age (by decade) was a significant predictor of developing bladder cancer (p < 0.0001). Incidence of bladder cancer was significantly different for either radiation or surgery alone versus no treatment, radiation versus surgery alone, and both surgery and radiation versus either modality alone (p < 0.0001). On multivariate analysis, age and irradiation were highly significant predictors of being diagnosed with bladder cancer. Conclusions: Following prostate cancer, increasing age and irradiation were highly significant predictors of being diagnosed with bladder cancer. While use of radiation increased the risk of bladder cancer compared to surgery alone or no treatment, the overall incidence of subsequent bladder cancer remained low. Routine bladder cancer surveillance is not warranted.

  13. Risk based neoadjuvant chemotherapy in muscle invasive bladder cancer

    PubMed Central

    Jayaratna, Isuru S.; Navai, Neema

    2015-01-01

    Muscle invasive bladder cancer (MIBC) is an aggressive disease that frequently requires radical cystectomy (RC) to achieve durable cure rates. Surgery is most effective when performed in organ-confined disease, with the best outcomes for those patients with a pT0 result. The goals of neoadjuvant chemotherapy (NC) are to optimize surgical outcomes for a malignancy with limited adjuvant therapies and a lack of effective salvage treatments. Despite level 1 evidence demonstrating a survival benefit, the utilization of NC has been hampered by several issues, including, the inability to predict responders and the perception that NC may delay curative surgery. In this article, we review the current efforts to identify patients that are most likely to derive a benefit from NC, in order to create a risk-adapted paradigm that reserves NC for those who need it. PMID:26816830

  14. Occupation and bladder cancer: a death-certificate study.

    PubMed Central

    Dolin, P. J.; Cook-Mozaffari, P.

    1992-01-01

    Occupational statements on death certificates of 2,457 males aged 25-64 who died from bladder cancer in selected coastal and estaurine regions of England and Wales during 1965-1980 were studied. Excess mortality was found for deck and engine room crew of ships, railway workers, electrical and electronic workers, shoemakers and repairers, and tobacco workers. An excess of cases also occurred among food workers, particularly those employed in the bread and flour confectionary industry or involved in the extraction of animal and vegetable oils and fats. Use of a job-exposure matrix revealed elevated risk for occupations in which most workers were exposed to paints and pigments, benzene and cutting oils. PMID:1520596

  15. Robotic surgery: review of prostate and bladder cancer.

    PubMed

    Sohn, William; Lee, Hak J; Ahlering, Thomas E

    2013-01-01

    Minimally invasive laparoscopic surgery has become to replace many of the open procedures in urology because of the obvious benefits in perioperative morbidity. However, because of the technical challenges and steep learning curve, the adoption of laparoscopy has been limited to only highly skilled laparoscopic surgeons. The introduction of the da Vinci surgical system (Intuitive Surgical Inc, Sunnyvale, Calif) has offered significant technical advantages over laparoscopic surgery. Because of the wide acceptance of robotic-assisted radical prostatectomy over the past decade, it has paved the way for urologists to tackle other complex operations, such as a radical cystectomy to decrease the morbidity of the operation. The goal of this article was to review the history and discuss the application and current status of the robot in both prostate and bladder cancer management. We present our technique of performing a robotic-assisted radical prostatectomy and the application of the robust prostate experience to robotic cystectomy. PMID:23528721

  16. Therapeutic potential of thalidomide for gemcitabine-resistant bladder cancer.

    PubMed

    Huang, Yen Ta; Cheng, Chuan Chu; Chiu, Ted H; Lai, Pei Chun

    2015-11-01

    Controversial effects of thalidomide for solid malignancies have been reported. In the present study, we evaluate the effects of thalidomide for transitional cell carcinoma (TCC), the most common type of bladder cancer. Thalidomide precipitates were observed when its DMSO solution was added to the culture medium. No precipitation was found when thalidomide was dissolved in 45% γ-cyclodextrin, and this concentration of γ-cyclodextrin elicited slight cytotoxicity on TCC BFTC905 and primary human urothelial cells. Thalidomide-γ-cyclodextrin complex exerted a concentration-dependent cytotoxicity in TCC cells, but was relatively less cytotoxic (with IC50 of 200 µM) in BFTC905 cells than the other 3 TCC cell lines, possibly due to upregulation of Bcl-xL and HIF-1α mediated carbonic anhydrase IX, and promotion of quiescence. Gemcitabine-resistant BFTC905 cells were chosen for additional experiments. Thalidomide induced apoptosis through downregulation of survivin and securin. The secretion of VEGF and TNF-α was ameliorated by thalidomide, but they did not affect cell proliferation. Immune-modulating lenalidomide and pomalidomide did not elicit cytotoxicity. In addition, cereblon did not play a role in the thalidomide effect. Oxidative DNA damage was triggered by thalidomide, and anti-oxidants reversed the effect. Thalidomide also inhibited TNF-α induced invasion through inhibition of NF-κB, and downregulation of effectors, ICAM-1 and MMP-9. Thalidomide inhibited the growth of BFTC905 xenograft tumors in SCID mice via induction of DNA damage and suppression of angiogenesis. Higher average body weight, indicating less chachexia, was observed in thalidomide treated group. Sedative effect was observed within one-week of treatment. These pre-clinical results suggest therapeutic potential of thalidomide for gemcitabine-resistant bladder cancer.

  17. Kaempferol suppresses bladder cancer tumor growth by inhibiting cell proliferation and inducing apoptosis.

    PubMed

    Dang, Qiang; Song, Wenbin; Xu, Defeng; Ma, Yanmin; Li, Feng; Zeng, Jin; Zhu, Guodong; Wang, Xinyang; Chang, Luke S; He, Dalin; Li, Lei

    2015-09-01

    The effects of the flavonoid compound, kaempferol, which is an inhibitor of cancer cell proliferation and an inducer of cell apoptosis have been shown in various cancers, including lung, pancreatic, and ovarian, but its effect has never been studied in bladder cancer. Here, we investigated the effects of kaempferol on bladder cancer using multiple in vitro cell lines and in vivo mice studies. The MTT assay results on various bladder cancer cell lines showed that kaempferol enhanced bladder cancer cell cytotoxicity. In contrast, when analyzed by the flow cytometric analysis, DNA ladder experiment, and TUNEL assay, kaempferol significantly was shown to induce apoptosis and cell cycle arrest. These in vitro results were confirmed in in vivo mice studies using subcutaneous xenografted mouse models. Consistent with the in vitro results, we found that treating mice with kaempferol significant suppression in tumor growth compared to the control group mice. Tumor tissue staining results showed decreased expressions of the growth related markers, yet increased expressions in apoptosis markers in the kaempferol treated group mice tissues compared to the control group mice. In addition, our in vitro and in vivo data showed kaempferol can also inhibit bladder cancer invasion and metastasis. Further mechanism dissection studies showed that significant down-regulation of the c-Met/p38 signaling pathway is responsible for the kaempferol mediated cell proliferation inhibition. All these findings suggest kaempferol might be an effective and novel chemotherapeutic drug to apply for the future therapeutic agent to combat bladder cancer.

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

    PubMed Central

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

    2015-01-01

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

  19. Bladder Preservation for Localized Muscle-Invasive Bladder Cancer: The Survival Impact of Local Utilization Rates of Definitive Radiotherapy

    SciTech Connect

    Kozak, Kevin R.; Hamidi, Maryam; Manning, Matthew; Moody, John S.

    2012-06-01

    Purpose: This study examines the management and outcomes of muscle-invasive bladder cancer in the United States. Methods and Materials: Patients with muscle-invasive bladder cancer diagnosed between 1988 and 2006 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Patients were classified according to three mutually exclusive treatment categories based on the primary initial treatment: no local management, radiotherapy, or surgery. Overall survival was assessed with Kaplan-Meier analysis and Cox models based on multiple factors including treatment utilization patterns. Results: The study population consisted of 26,851 patients. Age, sex, race, tumor grade, histology, and geographic location were associated with differences in treatment (all p < 0.01). Patients receiving definitive radiotherapy tended to be older and have less differentiated tumors than patients undergoing surgery (RT, median age 78 years old and 90.6% grade 3/4 tumors; surgery, median age 71 years old and 77.1% grade 3/4 tumors). No large shifts in treatment were seen over time, with most patients managed with surgical resection (86.3% for overall study population). Significant survival differences were observed according to initial treatment: median survival, 14 months with no definitive local treatment; 17 months with radiotherapy; and 43 months for surgery. On multivariate analysis, differences in local utilization rates of definitive radiotherapy did not demonstrate a significant effect on overall survival (hazard ratio, 1.002; 95% confidence interval, 0.999-1.005). Conclusions: Multiple factors influence the initial treatment strategy for muscle-invasive bladder cancer, but definitive radiotherapy continues to be used infrequently. Although patients who undergo surgery fare better, a multivariable model that accounted for patient and tumor characteristics found no survival detriment to the utilization of definitive radiotherapy. These results support continued

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

    SciTech Connect

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

    1986-11-01

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

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

    PubMed Central

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

    2015-01-01

    Bladder cancer has a high incidence with significant morbidity and mortality. Attenuated expression of the DNA damage response protein Xeroderma Pigmentosum complementation group C (XPC) has been described in bladder cancer. XPC plays an essential role as the main initiator and damage-detector in global genome nucleotide excision repair (NER) of UV-induced lesions, bulky DNA adducts and intrastrand crosslinks, such as those made by the chemotherapeutic agent Cisplatin. Hence, XPC protein might be an informative biomarker to guide personalized therapy strategies in a subset of bladder cancer cases. Therefore, we measured the XPC protein expression level and functional NER activity of 36 bladder tumors in a standardized manner. We optimized conditions for dissociation and in vitro culture of primary bladder cancer cells and confirmed attenuated XPC expression in approximately 40% of the tumors. However, NER activity was similar to co-cultured wild type cells in all but one of 36 bladder tumors. We conclude, that (i) functional NER deficiency is a relatively rare phenomenon in bladder cancer and (ii) XPC protein levels are not useful as biomarker for NER activity in these tumors. PMID:25927440

  2. Biomarkers in bladder cancer: A metabolomic approach using in vitro and ex vivo model systems.

    PubMed

    Rodrigues, Daniela; Jerónimo, Carmen; Henrique, Rui; Belo, Luís; de Lourdes Bastos, Maria; de Pinho, Paula Guedes; Carvalho, Márcia

    2016-07-15

    Metabolomics has recently proved to be useful in the area of biomarker discovery for cancers in which early diagnostic and prognostic biomarkers are urgently needed, as is the case of bladder cancer (BC). This article presents a comprehensive review of the literature on the metabolomic studies on BC, highlighting metabolic pathways perturbed in this disease and the altered metabolites as potential biomarkers for BC detection. Current disease model systems used in the study of BC metabolome include in vitro-cultured cancer cells, ex vivo neoplastic bladder tissues and biological fluids, mainly urine but also blood serum/plasma, from BC patients. The major advantages and drawbacks of each model system are discussed. Based on available data, it seems that BC metabolic signature is mainly characterized by alterations in metabolites related to energy metabolic pathways, particularly glycolysis, amino acid and fatty acid metabolism, known to be crucial for cell proliferation, as well as glutathione metabolism, known to be determinant in maintaining cellular redox balance. In addition, purine and pyrimidine metabolism as well as carnitine species were found to be altered in BC. Finally, it is emphasized that, despite the progress made in respect to novel biomarkers for BC diagnosis, there are still some challenges and limitations that should be addressed in future metabolomic studies to ensure their translatability to clinical practice. PMID:26804544

  3. [Cancer of the bladder occurring in occupational dye users: report of two cases].

    PubMed

    Ando, M; Takeda, H; Mizuo, T; Yokokawa, M; Ushiyama, T

    1984-02-01

    Two cases of occupational dye users were found to have bladder tumors. Case 1 was a 32-year-old male, who had worked at the Yuzen process for the last 7 years. Multiple papillary tumors were seen on the whole wall of the bladder endoscopically and total cysto-urethrectomy and ileal conduit were performed. The pathological examination of the bladder tumors revealed non-invasive transitional cell carcinoma grade I--II. His post-operative course has been uneventful without any signs of tumor recurrence for 31 months. Case 2 was a 46-year-old male, who had worked at the throwing stained silk for the last 28 years. He suffered from severe hematuria for six months. A big egg-sized nonpapillary tumor on the posterior wall of the bladder was found and bilateral cutaneous-ureterostomy was performed but severe gross hematuria remained. Total cysto-urethrectomy was performed but the patient died of progressive disease 5 months later. The bladder tumor was a grade III invasive transitional cell carcinoma. The fact that process workers in the dye manufacturing industry have a high risk of bladder cancer has been well known and mass screening examination on them has been systematically performed. Though there is a higher relative risk of bladder cancer in occupational dye users, systematic screening examination has not been done. We emphasize the necessity for establishing systematic mass screening examination of occupational dye users for the early diagnosis of bladder cancer.

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

    PubMed

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

    1990-08-01

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

  5. Non-steroidal anti-inflammatory drugs and bladder cancer prevention

    PubMed Central

    Castelao, J E; Yuan, J-M; Gago-Dominguez, M; Yu, M C; Ross, R K

    2000-01-01

    Inclusion of phenacetin among ‘proven’ human carcinogens by the IARC in 1987, raised concerns about the carcinogenic potential of acetaminophen, its major metabolite. Acetaminophen has been implicated as a possible causal agent in the development of cancer of the renal pelvis. The bladder and renal pelvis, which derive from the same embryological structure, share the same transitional type of epithelium. Past studies have been inconclusive on the possible relationship among these analgesics and bladder cancer but no large, highly detailed study of this association has been conducted. A population-based case–control study conducted in Los Angeles, California, involved 1514 incident bladder cancer cases and an equal number of controls who were matched to the index cases by sex, date of birth (within 5 years) and race. Detailed information on medication use and prior medical conditions was collected through in-person interviews. Regular use of analgesics was not associated with an increased risk of bladder cancer in either men or women. In fact, compared with non- or irregular users, regular analgesic users were at a decreased risk of bladder cancer overall (odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.68–0.96). However, there were clear differences in both the direction and strength of the associations between the different formulation classes of analgesics and bladder cancer risk. Intake of phenacetin was positively related to bladder cancer risk in a dose-dependent manner while intake of its major metabolite in humans, acetaminophen, was unrelated to risk. Intake of all classes of NSAIDs, except pyrazolon derivatives, were negatively associated with bladder cancer risk, with suggestive evidence that the protective effect varies in strength by subcategories of formulation. Acetic acids seemed to exhibit the strongest protective effect, whereas aspirin/other salicylic acids and oxicam showed the weakest protection. © 2000 Cancer Research Campaign

  6. Prognostic and therapeutic impact of argininosuccinate synthetase 1 control in bladder cancer as monitored longitudinally by PET imaging.

    PubMed

    Allen, Michael D; Luong, Phuong; Hudson, Chantelle; Leyton, Julius; Delage, Barbara; Ghazaly, Essam; Cutts, Rosalind; Yuan, Ming; Syed, Nelofer; Lo Nigro, Cristiana; Lattanzio, Laura; Chmielewska-Kassassir, Malgorzata; Tomlinson, Ian; Roylance, Rebecca; Whitaker, Hayley C; Warren, Anne Y; Neal, David; Frezza, Christian; Beltran, Luis; Jones, Louise J; Chelala, Claude; Wu, Bor-Wen; Bomalaski, John S; Jackson, Robert C; Lu, Yong-Jie; Crook, Tim; Lemoine, Nicholas R; Mather, Stephen; Foster, Julie; Sosabowski, Jane; Avril, Norbert; Li, Chien-Feng; Szlosarek, Peter W

    2014-02-01

    Targeted therapies have yet to have significant impact on the survival of patients with bladder cancer. In this study, we focused on the urea cycle enzyme argininosuccinate synthetase 1 (ASS1) as a therapeutic target in bladder cancer, based on our discovery of the prognostic and functional import of ASS1 in this setting. ASS1 expression status in bladder tumors from 183 Caucasian and 295 Asian patients was analyzed, along with its hypothesized prognostic impact and association with clinicopathologic features, including tumor size and invasion. Furthermore, the genetics, biology, and therapeutic implications of ASS1 loss were investigated in urothelial cancer cells. We detected ASS1 negativity in 40% of bladder cancers, in which multivariate analysis indicated worse disease-specific and metastasis-free survival. ASS1 loss secondary to epigenetic silencing was accompanied by increased tumor cell proliferation and invasion, consistent with a tumor-suppressor role for ASS1. In developing a treatment approach, we identified a novel targeted antimetabolite strategy to exploit arginine deprivation with pegylated arginine deiminase (ADI-PEG20) as a therapeutic. ADI-PEG20 was synthetically lethal in ASS1-methylated bladder cells and its exposure was associated with a marked reduction in intracellular levels of thymidine, due to suppression of both uptake and de novo synthesis. We found that thymidine uptake correlated with thymidine kinase-1 protein levels and that thymidine levels were imageable with [(18)F]-fluoro-L-thymidine (FLT)-positron emission tomography (PET). In contrast, inhibition of de novo synthesis was linked to decreased expression of thymidylate synthase and dihydrofolate reductase. Notably, inhibition of de novo synthesis was associated with potentiation of ADI-PEG20 activity by the antifolate drug pemetrexed. Taken together, our findings argue that arginine deprivation combined with antifolates warrants clinical investigation in ASS1-negative urothelial

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  10. Occupation, smoking, opium, and bladder cancer: A case–control study

    PubMed Central

    Ghadimi, Tayeb; Gheitasi, Bahman; Nili, Sayran; Karimi, Mohammad; Ghaderi, Ebrahim

    2015-01-01

    Purpose: The aim of this study was to investigate occupational risk factors associated with bladder cancer. Materials and Methods: In this case–control study, control group included patients who referred to a specialized clinic in the same city and hospitals where patients had been registered. Data were entered into SPSS software. Odds ratios (OR) were calculated for occupational variables and other characteristics. Then, using logistic regression, the association between cancer and drugs was studied while smoking was controlled. Results: Cigarette smoking, even after quitting, was also associated with bladder cancer (OR = 2.549). Considering the classification of occupations, the OR of working in metal industry in patients was 10.629. Multivariate analysis showed that use of the drug by itself can be a risk factor for bladder cancer. Drug abuse together with the control of smoking increased the risk of bladder cancer by 4.959. Conclusion: According to the findings of this study, contact with metal industries such as welding, and working with tin was found as a risk factor for bladder cancer. In addition, cigarette smoking and opium abuse individually were associated with bladder cancer. PMID:26942139

  11. Metformin for the Prevention of Bladder Cancer Recurrence: Is it Effective?

    PubMed Central

    Heidari, Fatemeh; Abbas Zade, Shahin; Mir Hosseini, Seyed Hassan; Ghadian, Alireza

    2016-01-01

    Background Many methods have been used for preventing and reducing recurrences of bladder cancers. In recent years, some investigators have examined the use of metformin for this purpose. First lines of evidence have shown that metformin inhibits cancer cell growth and prevents cancer occurrence in patients with type 2 diabetes. Objectives This study is designed to assess metformin usage in the prevention of bladder cancer recurrence after the trans-urethral resection of a bladder tumor (TUR-T). Patients and Methods In the present study, metformin was administered in the treatment of 32 patients with a history of bladder cancer, and their results were compared with those of 33 patients with bladder cancer recurrence (placebo group). Patients in the metformin group received 1000 mg metformin (2 tablets 500 mg) for 1 year. Frequency of tumor recurrence was calculated and compared with the placebo group. Results There was no statistical difference between the 2 groups with respect to the recurrence rate (P > 0.05). Although the recurrence interval was longer for the metformin group, this increase was not statistical significant (P > 0.05). Furthermore, tumor recurrence had no correlation with sex or the grade of the tumors. Conclusions According to our findings, it seems that metformin has no considerable inhibitory effect on the recurrence rate of bladder cancer, but that it can delay tumor recurrence. PMID:27570750

  12. Downregulation of DOCK1 sensitizes bladder cancer cells to cisplatin through preventing epithelial–mesenchymal transition

    PubMed Central

    Chen, Da-jin; Chen, Wei; Jiang, Hong; Yang, Hao; Wang, Yu-cheng; Chen, Jiang-hua

    2016-01-01

    During the past several decades, resistance to single or multiple anticancer agents has posed a great challenge in cancer therapy. Dedicator of cytokinesis 1 (DOCK1), the first identified member in DOCK family, plays diverse roles in cellular processes, including tumorigenesis. In this study, we explored the biological role of DOCK1 in the chemotherapeutic resistance in bladder cancer and its underlying mechanism. Our results showed that the bladder cancer cell lines UM-UC-3 and J82 with higher DOCK1 are more resistant to cisplatin, whereas B87 cells with the lowest expression of DOCK1 exhibited the highest sensitivity to cisplatin. Down-regulation of DOCK1 with small interfering RNA (siRNA) increased the cisplatin sensitivity in bladder cancer cells. Moreover, treatment with cisplatin induced epithelial–mesenchymal transition (EMT), while transfection with Twist siRNA restored the chemosensitivity to cisplatin. In addition, we found that downregulation of DOCK1 reversed EMT program in bladder cancer cells. However, cotransfection with DOCK1 siRNA could not further enhance the cisplatin sensitivity and cellular phenotypic changes in tumor cells. Taken together, these results demonstrate that downregulation of DOCK1 could increase the chemosensitivity in bladder cancer cells via preventing cisplatin-induced EMT, suggesting that DOCK1 may serve as a potential therapeutic target in bladder cancer.

  13. Tetrandrine reverses epithelial-mesenchymal transition in bladder cancer by downregulating Gli-1.

    PubMed

    Zhang, Yongjian; Liu, Wei; He, Wenbo; Zhang, Yuanyuan; Deng, Xiuling; Ma, Yanmin; Zeng, Jin; Kou, Bo

    2016-05-01

    Hedgehog (Hh) signaling pathway is considered to play a crucial role in vertebrate development and carcinogenesis. Additionally, epithelial-mesenchymal transition (EMT) is a cellular process during which epithelial cells become mesenchymal-appearing cells, facilitating cancer metastasis and invasion. Accumulating evidence has indicated that the Hh signaling pathway could potentiate the epithelial-mesenchymal transition (EMT). In the present study, we demonstrated that tetrandrine, a bisbenzylisoquinoline alkaloid isolated from Stephaniae, exerts its anti-metastatic ability in bladder cancer cells by regulating GLI family zinc finger 1 (Gli-1), a key factor of Hedgehog signaling pathway. In our study, we confirmed that tetrandrine could impede migration and invasion in bladder cancer 5637 and T24 cells. Additionally, tetrandrine reverses EMT by increasing the expression of E-cadherin and reducing the N-cadherin, vimentin and Slug expression in a dose-dependent manner. Interestingly, tetrandrine also decreases mobility and reduces the expression of Gli-1 in bladder cancer cells. Moreover, we verified that tetrandrine inhibits metastasis and induces mesenchymal-epithelial transition (MET) of bladder cancer through downregulation of Gli-1, which could be partially reversed by Gli-1 overexpression. In conclusion, our findings show that tetrandrine inhibits migration and invasion, and reverses EMT of bladder cancer cells through negatively regulating Gli-1. It indicates that Gli-1 may be a potential therapeutic target of tetrandrine against bladder cancer. PMID:26983576

  14. Downregulation of DOCK1 sensitizes bladder cancer cells to cisplatin through preventing epithelial–mesenchymal transition

    PubMed Central

    Chen, Da-jin; Chen, Wei; Jiang, Hong; Yang, Hao; Wang, Yu-cheng; Chen, Jiang-hua

    2016-01-01

    During the past several decades, resistance to single or multiple anticancer agents has posed a great challenge in cancer therapy. Dedicator of cytokinesis 1 (DOCK1), the first identified member in DOCK family, plays diverse roles in cellular processes, including tumorigenesis. In this study, we explored the biological role of DOCK1 in the chemotherapeutic resistance in bladder cancer and its underlying mechanism. Our results showed that the bladder cancer cell lines UM-UC-3 and J82 with higher DOCK1 are more resistant to cisplatin, whereas B87 cells with the lowest expression of DOCK1 exhibited the highest sensitivity to cisplatin. Down-regulation of DOCK1 with small interfering RNA (siRNA) increased the cisplatin sensitivity in bladder cancer cells. Moreover, treatment with cisplatin induced epithelial–mesenchymal transition (EMT), while transfection with Twist siRNA restored the chemosensitivity to cisplatin. In addition, we found that downregulation of DOCK1 reversed EMT program in bladder cancer cells. However, cotransfection with DOCK1 siRNA could not further enhance the cisplatin sensitivity and cellular phenotypic changes in tumor cells. Taken together, these results demonstrate that downregulation of DOCK1 could increase the chemosensitivity in bladder cancer cells via preventing cisplatin-induced EMT, suggesting that DOCK1 may serve as a potential therapeutic target in bladder cancer. PMID:27660415

  15. Risk of bladder cancer in renal transplant recipients: a meta-analysis

    PubMed Central

    Yan, L; Chen, P; Chen, E-Z; Gu, A; Jiang, Z-Y

    2014-01-01

    Background: Renal transplantation has been associated with a significantly increased risk of developing cancers during long-term follow-up, but for bladder cancer, this risk is less clear. We therefore performed a meta-analysis to determine whether bladder cancer risk in renal transplant recipients was increased. Methods: Eligible studies were identified through searches of PubMed and other public resources. Random-effects meta-analyses were used to pool overall estimates for standardised incidence ratios (SIRs). Heterogeneity test, sensitivity analysis, and assessment of publishing bias were also performed. Results: We identified a 3.18-fold higher SIR (95% confidence intervals (CI): 1.34–7.53, P=0.008) of bladder cancer in patients following renal transplantation compared with the general population, based on data from 79 988 patients with a total follow-up of 308 458 patient-years. When stratified by ethnicity, the SIRs for bladder cancer were 2.00 (95% CI: 1.51–2.65, P=0.001) and 14.74 (95% CI: 3.66–59.35, P<0.001) between European and Asian renal transplant recipients, respectively. Conclusions: Our study demonstrated that the risk of developing bladder cancer in transplant populations was increased. Such association suggests that physicians should be more vigilant in checking for bladder cancer in transplantation recipient population. PMID:24496458

  16. Incidence analyses of bladder cancer in the Nile delta region of Egypt.

    PubMed

    Fedewa, Stacey A; Soliman, Amr S; Ismail, Kadry; Hablas, Ahmed; Seifeldin, Ibrahim A; Ramadan, Mohamed; Omar, Hoda G; Nriagu, Jerome; Wilson, Mark L

    2009-10-01

    Bladder cancer is the most common malignancy among Egyptian males and previously has been attributed to Schistosoma infection, a major risk factor for squamous cell carcinoma (SCC). Recently, transitional cell carcinoma (TCC) incidence has been increasing while SCC has declined. To investigate this shift, we analyzed the geographical patterns of all bladder cancers cases recorded in Egypt's Gharbiah Population-Based Cancer Registry from 1999 through 2002. Data on tumor grade, stage, and morphology, as well as smoking, community of residence, age and sex, were collected on 1209 bladder cancer cases. Age-adjusted incidence rates were calculated for males, females, and the total population for the eight administrative Districts and 316 communities in Gharbiah. Incidence Rate Ratios (IRR) and 95% confidence intervals (CI) were computed using Poisson Regression. The male age-adjusted incidence rate (IR) in Gharbiah Province was 13.65/100,000 person years (PY). The District of Kotour had the highest age-adjusted IR 28.96/100,000 among males. The District of Kotour also had the highest IRR among all Districts, IRR=2.15 95% CI (1.72, 2.70). Kotour's capital city had the highest bladder cancer incidence among the 316 communities (IR=73.11/100,000 PY). Future studies on sources and types of environmental pollution and exposures in relation to the spatial patterns of bladder cancer, particularly in Kotour District, may improve our understating of risk factors for bladder cancer in the region. PMID:19762298

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

    PubMed Central

    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. PMID:27186419

  18. Downregulation of HIPK2 Increases Resistance of Bladder Cancer Cell to Cisplatin by Regulating Wip1

    PubMed Central

    Lin, Jun; Zhang, Qiang; Lu, Yi; Xue, Wenrui; Xu, Yue; Zhu, Yichen; Hu, Xiaopeng

    2014-01-01

    Cisplatin-based combination chemotherapy regimen is a reasonable alternative to cystectomy in advanced/metastatic bladder cancer, but acquisition of cisplatin resistance is common in patients with bladder cancer. Previous studies showed that loss of homeodomain-interacting protein kinase-2 (HIPK2) contributes to cell proliferation and tumorigenesis. However, the role of HIPK2 in regulating chemoresistance of cancer cell is not fully understood. In the present study, we found that HIPK2 mRNA and protein levels are significantly decreased in cisplatin-resistant bladder cancer cell in vivo and in vitro. Downregulation of HIPK2 increases the cell viability in a dose- and time-dependent manner during cisplatin treatment, whereas overexpression of HIPK2 reduces the cell viability. HIPK2 overexpression partially overcomes cisplatin resistance in RT4-CisR cell. Furthermore, we showed that Wip1 (wild-type p53-induced phosphatase 1) expression is upregulated in RT4-CisR cell compared with RT4 cell, and HIPK2 negatively regulates Wip1 expression in bladder cancer cell. HIPK2 and Wip1 expression is also negatively correlated after cisplatin-based combination chemotherapy in vivo. Finally, we demonstrated that overexpression of HIPK2 sensitizes chemoresistant bladder cancer cell to cisplatin by regulating Wip1 expression. Conclusions These data suggest that HIPK2/Wip1 signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of bladder cancer. PMID:24846322

  19. Incidence analyses of bladder cancer in the Nile delta region of Egypt

    PubMed Central

    Fedewa, Stacey A.; Soliman, Amr S.; Ismail, Kadry; Hablas, Ahmed; Seifeldin, Ibrahim A.; Ramadan, Mohamed; Omar, Hoda G.; Nriagu, Jerome; Wilson, Mark L.

    2009-01-01

    Bladder cancer is the most common malignancy among Egyptian males and previously has been attributed to Schistosoma infection, a major risk factor for squamous cell carcinoma (SCC). Recently, transitional cell carcinoma (TCC) incidence has been increasing while SCC has declined. To investigate this shift, we analyzed the geographical patterns of all bladder cancers cases recorded in Egypt’s Gharbiah Population-Based Cancer Registry from 1999 through 2002. Data on tumor grade, stage, and morphology, as well as smoking, community of residence, age and sex, were collected on 1,209 bladder cancer cases. Age-adjusted incidence rates were calculated for males, females, and the total population for the eight administrative Districts and 316 communities in Gharbiah. Incidence Rate Ratios (IRR) and 95% Confidence Intervals (CI) were computed using Poisson Regression. The male age-adjusted incidence rate (IR) in Gharbiah Province was 13.65/100,000 person years (PY). The District of Kotour had the highest age-adjusted IR 28.96/100,000 among males. The District of Kotour also had the highest IRR among all Districts, IRR=2.15 95% CI (1.72, 2.70). Kotour’s capital city had the highest bladder cancer incidence among the 316 communities (IR=73.11/100,000 PY). Future studies on sources and types of environmental pollution and exposures in relation to the spatial patterns of bladder cancer, particularly in Kotour District, may improve our understating of risk factors for bladder cancer in the region. PMID:19762298

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

    PubMed

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

    2008-01-01

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

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

    Cancer.gov

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

  2. [Clinical assessment of thermoradiotherapy of breast cancer and cancer of the urinary bladder].

    PubMed

    Hiraoka, M; Masunaga, S; Nishimura, Y; Nagata, Y; Li, Y P; Koishi, M; Mitsumori, M; Abe, M; Takahashi, M; Akuta, K

    1990-10-01

    Non-randomized clinical trials of thermoradiotherapy for breast cancer and carcinoma of the urinary bladder were reported. Thermoradiotherapy was useful for breast cancer treatment in term of (1) increased local control for locally advanced tumors and (2) possibility of reducing dose of irradiation for recurrent tumors following radiotherapy. Tumor response to thermoradiotherapy was dependent on tumor volume and maximum or minimum tumor temperature. Thermoradiotherapy was also effective as a preoperative-treatment for urinary bladder cancer. The incidence of down-staging and degeneration of tumors was significantly higher in thermoradiotherapy than in radiotherapy. These effects were temperature dependent. Patients with T 3-4 NOMO or Grade 3 tumors treated with thermoradiotherapy showed a tendency of increased survival compared with those treated with radiotherapy alone. PMID:2250346

  3. Molecular events underlying schistosomiasis-related bladder cancer.

    PubMed

    Ramchurren, N; Cooper, K; Summerhayes, I C

    1995-07-28

    Twenty-one invasive squamous-cell carcinomas (SCC) of the bladder from Schistosoma-hematobium-infected patients were examined immunohistochemically for the expression of p53, Rb, EGFR and c-erbB-2 proteins; and screened by single-strand conformation polymorphism and sequencing for mutations in the ras (H, N, K) codon hotspots (12, 13, 61) and p53 (exons 4-9) genes. Positive staining for p53, EGFR and c-erbB-2 was reported in 38, 67 and 28% of tumors respectively. Only one of the tumors, the only one that was poorly differentiated, displayed an absence of nuclear Rb staining. Ras alterations were detected in the H-ras gene in 3 tumors, 2 of which harbored a codon-13 (Gly-->Arg) and one a codon-12 (Gly-->Ser) point mutation. p53 mutations were recorded in 12 tumors (57%), 6 of which stained positively for p53. Four tumors had exon-7 mutations (codons 235, 241 and 249; one tumor had 2 exon-7 mutations). Eight tumors were mutated in exon 8 (codons 264, 271, 273, 285, 286, 288 and 294), 5 of which harbored multiple mutations. One tumor had an insertion/deletion event in exon 9. The frequency of detection of over-expression of EGFR and c-erbB-2 in bilharzial-bladder lesions is comparable to that reported in TCC, contrasting with the infrequent loss of Rb expression found in invasive lesions associated with schistosomiasis infection. However, the detection of multiple p53 mutations in these lesions is suggestive of the involvement of a carcinogenic agent with maintenance of preferential activation of the H-ras gene. PMID:7628866

  4. Novel theranostic nanoporphyrins for photodynamic diagnosis and trimodal therapy for bladder cancer.

    PubMed

    Lin, Tzu-Yin; Li, Yuanpei; Liu, Qiangqiang; Chen, Jui-Lin; Zhang, Hongyong; Lac, Diana; Zhang, Hua; Ferrara, Katherine W; Wachsmann-Hogiu, Sebastian; Li, Tianhong; Airhart, Susan; deVere White, Ralph; Lam, Kit S; Pan, Chong-Xian

    2016-10-01

    The overall prognosis of bladder cancer has not been improved over the last 30 years and therefore, there is a great medical need to develop novel diagnosis and therapy approaches for bladder cancer. We developed a multifunctional nanoporphyrin platform that was coated with a bladder cancer-specific ligand named PLZ4. PLZ4-nanoporphyrin (PNP) integrates photodynamic diagnosis, image-guided photodynamic therapy, photothermal therapy and targeted chemotherapy in a single procedure. PNPs are spherical, relatively small (around 23 nm), and have the ability to preferably emit fluorescence/heat/reactive oxygen species upon illumination with near infrared light. Doxorubicin (DOX) loaded PNPs possess slower drug release and dramatically longer systemic circulation time compared to free DOX. The fluorescence signal of PNPs efficiently and selectively increased in bladder cancer cells but not normal urothelial cells in vitro and in an orthotopic patient derived bladder cancer xenograft (PDX) models, indicating their great potential for photodynamic diagnosis. Photodynamic therapy with PNPs was significantly more potent than 5-aminolevulinic acid, and eliminated orthotopic PDX bladder cancers after intravesical treatment. Image-guided photodynamic and photothermal therapies synergized with targeted chemotherapy of DOX and significantly prolonged overall survival of mice carrying PDXs. In conclusion, this uniquely engineered targeting PNP selectively targeted tumor cells for photodynamic diagnosis, and served as effective triple-modality (photodynamic/photothermal/chemo) therapeutic agents against bladder cancers. This platform can be easily adapted to individualized medicine in a clinical setting and has tremendous potential to improve the management of bladder cancer in the clinic.

  5. Novel theranostic nanoporphyrins for photodynamic diagnosis and trimodal therapy for bladder cancer.

    PubMed

    Lin, Tzu-Yin; Li, Yuanpei; Liu, Qiangqiang; Chen, Jui-Lin; Zhang, Hongyong; Lac, Diana; Zhang, Hua; Ferrara, Katherine W; Wachsmann-Hogiu, Sebastian; Li, Tianhong; Airhart, Susan; deVere White, Ralph; Lam, Kit S; Pan, Chong-Xian

    2016-10-01

    The overall prognosis of bladder cancer has not been improved over the last 30 years and therefore, there is a great medical need to develop novel diagnosis and therapy approaches for bladder cancer. We developed a multifunctional nanoporphyrin platform that was coated with a bladder cancer-specific ligand named PLZ4. PLZ4-nanoporphyrin (PNP) integrates photodynamic diagnosis, image-guided photodynamic therapy, photothermal therapy and targeted chemotherapy in a single procedure. PNPs are spherical, relatively small (around 23 nm), and have the ability to preferably emit fluorescence/heat/reactive oxygen species upon illumination with near infrared light. Doxorubicin (DOX) loaded PNPs possess slower drug release and dramatically longer systemic circulation time compared to free DOX. The fluorescence signal of PNPs efficiently and selectively increased in bladder cancer cells but not normal urothelial cells in vitro and in an orthotopic patient derived bladder cancer xenograft (PDX) models, indicating their great potential for photodynamic diagnosis. Photodynamic therapy with PNPs was significantly more potent than 5-aminolevulinic acid, and eliminated orthotopic PDX bladder cancers after intravesical treatment. Image-guided photodynamic and photothermal therapies synergized with targeted chemotherapy of DOX and significantly prolonged overall survival of mice carrying PDXs. In conclusion, this uniquely engineered targeting PNP selectively targeted tumor cells for photodynamic diagnosis, and served as effective triple-modality (photodynamic/photothermal/chemo) therapeutic agents against bladder cancers. This platform can be easily adapted to individualized medicine in a clinical setting and has tremendous potential to improve the management of bladder cancer in the clinic. PMID:27479049

  6. Loss of GATA3 in bladder cancer promotes cell migration and invasion.

    PubMed

    Li, Yi; Ishiguro, Hitoshi; Kawahara, Takashi; Kashiwagi, Eiji; Izumi, Koji; Miyamoto, Hiroshi

    2014-04-01

    The transcription factor GATA3 is known as a breast tumor suppressor as well as a urothelial marker, and its loss is often seen in high-grade invasive bladder cancer. Nonetheless, GATA3 functions in bladder cancer cells remain largely unknown. In this study, we assessed the effects of GATA3 silencing via RNA interference on cell migration, invasion, and proliferation of bladder cancer. GATA3 expression was downregulated in all four bladder cancer lines examined, compared with a non-neoplastic urothelial line SVHUC. Knockdown of GATA3 in the bladder cancer lines (5637, TCC-SUP, J82) resulted in promotion of cell migration and invasion as well as increases in the expression of their related molecules, such as vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9, and the activity of MMP-2 and MMP-9. GATA3 loss was also associated with an increasing level of a mesenchymal marker N-cadherin and a decreasing level of an epithelial marker β-catenin. Consistent with these findings, enforced expression of GATA3 in UMUC3 inhibited cell migration and invasion. However, GATA3 showed marginal effects on bladder cancer cell viability and the expression of cell cycle- or apoptosis-related molecules. Additionally, in contrast to bladder cancer lines, no significant effects of GATA3 silencing on cell migration were seen in SVHUC. These findings suggest that GATA3 plays an important role in the prevention of bladder cancer progression and metastasis by inhibiting cell migration and invasion as well as epithelial-to-mesenchymal transition.

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

    PubMed

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

    2016-04-01

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

  8. CXCL5 knockdown expression inhibits human bladder cancer T24 cells proliferation and migration

    SciTech Connect

    Zheng, Jiajia; Zhu, Xi; Zhang, Jie

    2014-03-28

    Highlights: • We first demonstrated CXCL5 is highly expressed in human bladder tumor tissues and cells. • CXCL5 knockdown inhibits proliferation, migration and promotes apoptosis in T24 cells. • CXCL5 knockdown inhibits Snail, PI3K-AKT and ERK1/2 signaling pathways in T24 cells. • CXCL5 is critical for bladder tumor growth and progression. - Abstract: CXCL5 (epithelial neutrophil activating peptide-78) which acts as a potent chemoattractant and activator of neutrophil function was reported to play a multifaceted role in tumorigenesis. To investigate the role of CXCL5 in bladder cancer progression, we examined the CXCL5 expression in bladder cancer tissues by real-time PCR and Western blot, additionally, we used shRNA-mediated silencing to generate stable CXCL5 silenced bladder cancer T24 cells and defined its biological functions. Our results demonstrated that mRNA and protein of CXCL5 is increased in human bladder tumor tissues and cell lines, down-regulation of CXCL5 in T24 cells resulted in significantly decreased cell proliferation, migration and increased cell apoptosis in vitro through Snail, PI3K-AKT and ERK1/2 signaling pathways. These data suggest that CXCL5 is critical for bladder tumor growth and progression, it may represent a potential application in cancer diagnosis and therapy.

  9. The Reversal Effect and Its Mechanisms of Tetramethylpyrazine on Multidrug Resistance in Human Bladder Cancer

    PubMed Central

    Wang, Shanshan; Lei, Ting; Zhang, Man

    2016-01-01

    Chemotherapy is an important strategy for the treatment of bladder cancer. However, the main problem limiting the success of chemotherapy is the development of multidrug resistance (MDR). To improve the management of bladder cancer, it is an urgent matter to search for strategies to reverse MDR. We chose three kinds of herbal medicines including ginsenoside Rh2, (-)-Epigallocatechin gallate (EGCG) and Tetramethylpyrazine (TMP) to detect their effects on bladder cancer. Reversal effects of these three herbal medicines for drug resistance in adriamycin (ADM)-resistant Pumc-91 cells (Pumc-91/ADM) were assessed by Cell Counting Kit-8 (CCK-8) cell proliferation assay system. The mechanisms of reversal effect for TMP were explored in Pumc-91/ADM and T24/DDP cells. After Pumc-91/ADM and T24/DDP cells were treated with TMP, cell cycle distribution analysis was performed by flow cytometry. The expression of MRP1, GST, BCL-2, LRP and TOPO-II was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR), immunefluorescence assay and western blot. It was observed that TMP was capable of enhancing the cytotoxicity of anticancer agents on Pumc-91/ADM cells in response to ADM, however Rh2 and EGCG were unable to. The reversal effect of TMP was also demonstrated in T24/DDP cells. Moreover, the treatment with TMP in Pumc-91/ADM and T24/DDP cells led to an increased of G1 phase accompanied with a concomitant decrease of cell numbers in S phase. Compared to the control group, an obvious decrease of MRP1, GST, BCL-2 and an increase of TOPO-II were shown in TMP groups with a dose-dependency in mRNA and protein levels. However, there was no difference on LRP expression between TMP groups and the control group. TMP could effectively reverse MDR of Pumc-91/ADM and T24/DDP cells and its mechanisms might be correlated with the alteration of MRP1, GST, BCL-2 and TOPO-II. TMP might be a potential candidate for reversing drug resistance in bladder cancer chemotherapy. PMID

  10. The Reversal Effect and Its Mechanisms of Tetramethylpyrazine on Multidrug Resistance in Human Bladder Cancer.

    PubMed

    Wang, Shanshan; Lei, Ting; Zhang, Man

    2016-01-01

    Chemotherapy is an important strategy for the treatment of bladder cancer. However, the main problem limiting the success of chemotherapy is the development of multidrug resistance (MDR). To improve the management of bladder cancer, it is an urgent matter to search for strategies to reverse MDR. We chose three kinds of herbal medicines including ginsenoside Rh2, (-)-Epigallocatechin gallate (EGCG) and Tetramethylpyrazine (TMP) to detect their effects on bladder cancer. Reversal effects of these three herbal medicines for drug resistance in adriamycin (ADM)-resistant Pumc-91 cells (Pumc-91/ADM) were assessed by Cell Counting Kit-8 (CCK-8) cell proliferation assay system. The mechanisms of reversal effect for TMP were explored in Pumc-91/ADM and T24/DDP cells. After Pumc-91/ADM and T24/DDP cells were treated with TMP, cell cycle distribution analysis was performed by flow cytometry. The expression of MRP1, GST, BCL-2, LRP and TOPO-II was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR), immunefluorescence assay and western blot. It was observed that TMP was capable of enhancing the cytotoxicity of anticancer agents on Pumc-91/ADM cells in response to ADM, however Rh2 and EGCG were unable to. The reversal effect of TMP was also demonstrated in T24/DDP cells. Moreover, the treatment with TMP in Pumc-91/ADM and T24/DDP cells led to an increased of G1 phase accompanied with a concomitant decrease of cell numbers in S phase. Compared to the control group, an obvious decrease of MRP1, GST, BCL-2 and an increase of TOPO-II were shown in TMP groups with a dose-dependency in mRNA and protein levels. However, there was no difference on LRP expression between TMP groups and the control group. TMP could effectively reverse MDR of Pumc-91/ADM and T24/DDP cells and its mechanisms might be correlated with the alteration of MRP1, GST, BCL-2 and TOPO-II. TMP might be a potential candidate for reversing drug resistance in bladder cancer chemotherapy. PMID

  11. Effects of Androgen and Estrogen Receptor Signaling Pathways on Bladder Cancer Initiation and Progression

    PubMed Central

    Godoy, Guilherme; Gakis, Georgios; Smith, Carolyn L.; Fahmy, Omar

    2016-01-01

    Epidemiologic studies have long demonstrated clear differences in incidence and progression of bladder cancer between genders suggesting that the mechanisms of development and progression in these tumors have a strong association with steroid hormonal pathways. Such observations led to preclinical studies investigating the role of androgen and estrogen receptors, as well as their cognate hormones in bladder cancer initiation and progression. Using various in vitro cell line assays and in vivo mouse models, studies have elucidated different mechanisms and signaling pathways through which these steroid receptors may participate in this disease. More recently, RNA expression data from multiple studies revealed a luminal subtype of bladder cancer that exhibited an estrogen receptor signaling pathway, making it a strong candidate for further consideration of targeted therapies in the future. Despite the promising preclinical data demonstrating potential roles for both antiandrogen and antiestrogen strategies targeting these pathways in different stages of bladder cancer, only two clinical trials are currently active and accruing patients for such clinical studies. Targeted therapies in bladder cancer are a large unmet need and have the potential to change treatment paradigms and improve oncological outcomes of patients with bladder cancer. PMID:27376135

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

    PubMed

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

    2015-01-01

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

  13. Prognostic significance of mucin expression in urothelial bladder cancer

    PubMed Central

    Stojnev, Slavica; Ristic-Petrovic, Ana; Velickovic, Ljubinka Jankovic; Krstic, Miljan; Bogdanovic, Dragan; Khanh, Do Throng; Ristic, Ana; Conic, Irena; Stefanovic, Vladisav

    2014-01-01

    Urothelial bladder cancer (UBC) is a common genitourinary malignancy, accounting for more than 160.000 deaths per year worldwide. Overexpression and aberrant glycosylation of mucins are frequent traits of many human cancers derived from epithelial cells, and are found to have prognostic significance in various carcinomas. The aim of this study was to further elucidate the features and significance of mucin expression in UBC. We investigated the relationship between mucin expression and clinicopathological characteristics in 539 cases of UBC by immunohistochemical analysis of MUC1, MUC2, MUC4, MUC5AC and MUC6 expression profiles. MUC1 stained 61.8% of the tumors and correlated with high tumor grade (P = 0.013). The expression of MUC2 and MUC6 was associated with low tumor grade (P < 0.000 and P < 0.022, respectively), and low pathologic stage (P < 0.001 and P = 0.001, respectively). MUC2 negative tumors were more frequently associated with the finding of carcinoma in situ in tumor surroundings (P = 0.019). UBC with divergent differentiation correlated with MUC1, MUC4 and MUC5AC staining. MUC4 expression was directly linked to cancer specific death (P = 0.027), while MUC2 and MUC6 showed inverse correlation to cancer-specific death (P < 0.001 and P = 0.005, respectively). Kaplan-Meier analyses showed that expression of MUC2 and MUC6 in UBC was significantly associated with better overall survival of the patients (P < 0.001, respectively). In Cox regression model, the absence of MUC6 expression emerged as independent predictor of death outcome. In conclusion, this study identifies MUC2 and MUC6 expression as markers of UBC with less aggressive behavior and useful predictors of better survival. PMID:25197366

  14. Systemic chemotherapy in inoperable or metastatic bladder cancer.

    PubMed

    Bamias, A; Tiliakos, I; Karali, M-D; Dimopoulos, M A

    2006-04-01

    Urothelial cancer is a common malignancy. The management of patients with recurrent disease after cystectomy or initially metastatic or unresectable disease represents a therapeutic challenge. Systemic chemotherapy prolongs survival but long-term survival remains infrequent. During recent years there has been improvement due to the use of novel chemotherapeutic agents, mainly gemcitabine and the taxanes. The long-considered-standard MVAC has been challenged by combinations showing more favourable toxicity profiles and equal (gemcitabine-cisplatin) or even improved (dose-dense, G-CSF-supported MVAC) efficacy. Specific interest has also been generated in specific groups of patients (elderly patients, patients with renal function impairment or comorbidities), who are not fit for the standard cisplatin-based chemotherapy but can derive significant benefit from carboplatin- or taxane-based treatment. Retrospective analyses have enabled the identification of groups of patients with different prognoses, who possibly require different therapeutic approaches. Modern chemotherapy offers a chance of long-term survival in patients without visceral metastases, possibly in combination with definitive local treatment. Finally, the progress of targeted therapies in other neoplasms seems to be reflected in advanced bladder cancer by recent studies indicating that biological agents can be combined with modern chemotherapy. The true role of such therapies is currently being evaluated. PMID:16303860

  15. Low-grade toxicity after conformal radiation therapy for prostate cancer-impact of bladder volume

    SciTech Connect

    Pinkawa, Michael . E-mail: mpinkawa@ukaachen.de; Fischedick, Karin; Asadpour, Branka; Gagel, Bernd; Piroth, Marc D.; Eble, Michael J.

    2006-03-01

    Purpose: To assess the impact of dose-volume histogram parameters on low-grade toxicity after radiotherapy for prostate cancer. Methods and Materials: Eighty patients have been surveyed prospectively before (time A), at the last day (B), 2 months after (C), and 16 months (median) after (D) radiotherapy (70.2 Gy) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Dose-volume histograms were correlated with urinary and bowel function/bother scores. Results: The initial bladder volume and the percentage of the bladder volume receiving 10%-90% of the prescription dose significantly correlated with urinary function/bother scores (significant cutoff levels found for all dose levels). Pain with urination proved to be mainly an acute problem, subsiding faster for patients with larger bladder volumes and smaller volumes inside particular isodose lines. At time D, persisting problems with smaller initial bladder volumes were a weak stream and an increased frequency of urination. Though bladder volume and planning target volume both independently have an influence on dose-volume histogram parameters for the bladder, bladder volume plays the decisive role for urinary toxicity. Conclusions: The patient's ability to fill the bladder has a major impact on the dose-volume histogram and both acute and late urinary toxicity.

  16. Bladder cancers respond to intravesical instillation of HAMLET (human alpha-lactalbumin made lethal to tumor cells).

    PubMed

    Mossberg, Ann-Kristin; Wullt, Björn; Gustafsson, Lotta; Månsson, Wiking; Ljunggren, Eva; Svanborg, Catharina

    2007-09-15

    We studied if bladder cancers respond to HAMLET (human alpha-lactalbumin made lethal to tumor cells) to establish if intravesical HAMLET application might be used to selectively remove cancer cells in vivo. Patients with nonmuscle invasive transitional cell carcinomas were included. Nine patients received 5 daily intravesical instillations of HAMLET (25 mg/ml) during the week before scheduled surgery. HAMLET stimulated a rapid increase in the shedding of tumor cells into the urine, daily, during the 5 days of instillation. The effect was specific for HAMLET, as intravesical instillation of NaCl, PBS or native alpha-lactalbumin did not increase cell shedding. Most of the shed cells were dead and an apoptotic response was detected in 6 of 9 patients, using the TUNEL assay. At surgery, morphological changes in the exophytic tumors were documented by endoscopic photography and a reduction in tumor size or change in tumor character was detected in 8 of 9 patients. TUNEL staining was positive in biopsies from the remaining tumor in 4 patients but adjacent healthy tissue showed no evidence of apoptosis and no toxic response. The results suggest that HAMLET exerts a direct and selective effect on bladder cancer tissue in vivo and that local HAMLET administration might be of value in the future treatment of bladder cancers.

  17. ELK1 is up-regulated by androgen in bladder cancer cells and promotes tumor progression

    PubMed Central

    Aljarah, Ali Kadhim; Ide, Hiroki; Li, Yi; Kashiwagi, Eiji; Netto, George J.; Zheng, Yichun; Miyamoto, Hiroshi

    2015-01-01

    Little is known about biological significance of ELK1, a transcriptional factor that activates downstream targets including c-fos proto-oncogene, in bladder cancer. Recent preclinical evidence also suggests the involvement of androgen receptor (AR) signaling in bladder cancer progression. In this study, we aim to investigate the functions of ELK1 in bladder cancer growth and their regulation by AR signals. Immunohistochemistry in bladder tumor specimens showed that the levels of phospho-ELK1 (p-ELK1) expression were significantly elevated in urothelial neoplasms, compared with non-neoplastic urothelium tissues, and were also correlated with AR positivity. Patients with p-ELK1-positive non-muscle-invasive and muscle-invasive tumors had significantly higher risks for tumor recurrence and progression, respectively. In AR-positive bladder cancer cell lines, dihydrotestosterone treatment increased ELK1 expression (mRNA, protein) and its nuclear translocation, ELK1 transcriptional activity, and c-fos expression, which was restored by an anti-androgen hydroxyflutamide. ELK1 silencing via short hairpin RNA (shRNA) resulted in decreases in cell viability/colony formation, and cell migration/invasion as well as an increase in apoptosis. Importantly, ELK1 appears to require activated AR to regulate bladder cancer cell proliferation, but not cell migration. Androgen also failed to significantly induce AR transactivation in ELK1-knockdown cells. In accordance with our in vitro findings, ELK1-shRNA expression considerably retarded tumor formation as well as its growth in xenograft-bearing male mice. Our results suggest that ELK1 plays an important role in bladder tumorigenesis and cancer progression, which is further induced by AR activation. Accordingly, ELK1 inhibition, together with AR inactivation, has the potential of being a therapeutic approach for bladder cancer. PMID:26342199

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

    NASA Astrophysics Data System (ADS)

    Yang, Xiao-feng; Pang, Jian-zhi; Liu, Jie-hao; Zhao, Yang; Jia, Xing-you; Li, Jun; Liu, Reng-xin; Wang, Wei; Fan, Zhen-wei; Zhang, Zi-qiang; Yan, San-hua; Luo, Jun-qian; Zhang, Xiao-lei

    2014-11-01

    Background: The limitations of primary transurethral resection of bladder tumor (TURBt) have led the residual tumors rates as high as 75%. The intraoperative fluorescence imaging offers a great potential for improving TURBt have been confirmed. So we aim to distinguish the residual tumors and normal mucosa using fluorescence molecular imaging formed by conjugated molecule of the CSNRDARRC bladder cancer homing peptide with fluorescent dye. The conjugated molecule was abbreviated FIuo-ACP. In our study, we will research the image features of FIuo-ACP probe targeted bladder cancer for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo. Methods: After the FIuo-ACP probe was synthetized, the binding sites, factors affecting binding rates, the specificity and the targeting of Fluo-ACP labeled with bladder cancer cells were studied respectively by laser scanning confocal microscope (LSCM), immunofluorescence and multispectral fluorescence ex vivo optical molecular imaging system. Results: The binding sites were located in nucleus and the binding rates were correlated linearly with the dose of probe and the grade of pathology. Moreover, the probe has a binding specificity with bladder cancer in vivo and ex vivo. Tumor cells being labeled by the Fluo-ACP, bright green spots were observed under LSCM. The tissue samples and tumor cells can be labeled and identified by fluorescence microscope. Optical molecular imaging of xenograft tumor tissues was exhibited as fluorescent spots under EMCCD. Conclusion: The CSNRDARRC peptides might be a useful bladder cancer targeting vector. The FIuo-ACP molecular probe was suitable for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo.

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

    PubMed

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

    2010-12-01

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

  20. [Short version of the German S3 guideline for bladder cancer].

    PubMed

    Retz, M; Gschwend, J E; Maisch, P

    2016-09-01

    Urinary bladder cancer is the second most common cancer of the urogenital system. The Guideline Program in Oncology (Leitlinienprogramm Onkologie) of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF), the German Cancer Society (Deutsche Krebsgesellschaft) and the German Cancer Aid (Deutsche Krebshilfe) as well as 31 different medical societies have developed the first interdisciplinary, evidence-based German guideline for bladder cancer. This short version presents the resulting series of diagnostic and therapeutic recommendations which were based on a systematic literature search and approved by a team of bladder cancer experts. The full version is available under http://leitlinienprogramm-onkologie.de/ .

  1. Frequencies of poor metabolizers of cytochrome P450 2C19 in esophagus cancer, stomach cancer, lung cancer and bladder cancer in Chinese population

    PubMed Central

    Shi, Wei-Xing; Chen, Shu-Qing

    2004-01-01

    AIM: To investigate the association between cytochrome P450 2C19 (CYP2C19) gene polymorphism and cancer susceptibility by genotyping of CYP2C19 poor metabolizers (PMs) in cancer patients. METHODS: One hundred and thirty-five cases of esophagus cancer, 148 cases of stomach cancer, 212 cases of lung cancer, 112 cases of bladder cancer and 372 controls were genotyped by allele specific amplification-polymerase chain reaction (ASA-PCR) for CYP2C19 PMs. The frequencies of PMs in cancer groups and control group were compared. RESULTS: The frequencies of PMs of CYP2C19 were 34.1% (46/135) in the group of esophagus cancer patients, 31.8% (47/148) in the stomach cancer patients, 34.4% (73/212) in the group of lung cancer patients, only 4.5% (5/112) in the bladder cancer patients and 14.0% (52/372) in control group. There were statistical differences between the cancer groups and control group (esophagus cancer, χ2 = 25.65, P < 0.005, OR = 3.18, 95%CI = 2.005-5.042; stomach cancer, χ2 = 21.70, P < 0.005, OR = 2.86, 95%CI = 1.820-4.501; lung cancer, χ2 = 33.58, P < 0.005, OR = 3.23, 95%CI = 1.503-6.906; bladder cancer, χ2 = 7.50, P < 0.01, OR = 0.288, 95%CI = 0.112-0.740). CONCLUSION: CYP2C19 PMs have a high incidence of esophagus cancer, stomach cancer and lung cancer, conversely they have a low incidence of bladder cancer. It suggests that CYP2C19 may participate in the activation of procarcinogen of esophagus cancer, stomach cancer and lung cancer, but may involve in the detoxification of carcinogens of bladder cancer. PMID:15222046

  2. Integrative Pathway Analysis of Metabolic Signature in Bladder Cancer: A Linkage to The Cancer Genome Atlas Project and Prediction of Survival

    PubMed Central

    von Rundstedt, Friedrich-Carl; Rajapakshe, Kimal; Ma, Jing; Arnold, James M.; Gohlke, Jie; Putluri, Vasanta; Krishnapuram, Rashmi; Piyarathna, D. Badrajee; Lotan, Yair; Gödde, Daniel; Roth, Stephan; Störkel, Stephan; Levitt, Jonathan M.; Michailidis, George; Sreekumar, Arun; Lerner, Seth P.; Coarfa, Cristian; Putluri, Nagireddy

    2016-01-01

    Purpose We used targeted mass spectrometry to study the metabolic fingerprint of urothelial cancer and determine whether the biochemical pathway analysis gene signature would have a predictive value in independent cohorts of patients with bladder cancer. Materials and Methods Pathologically evaluated, bladder derived tissues, including benign adjacent tissue from 14 patients and bladder cancer from 46, were analyzed by liquid chromatography based targeted mass spectrometry. Differential metabolites associated with tumor samples in comparison to benign tissue were identified by adjusting the p values for multiple testing at a false discovery rate threshold of 15%. Enrichment of pathways and processes associated with the metabolic signature were determined using the GO (Gene Ontology) Database and MSigDB (Molecular Signature Database). Integration of metabolite alterations with transcriptome data from TCGA (The Cancer Genome Atlas) was done to identify the molecular signature of 30 metabolic genes. Available outcome data from TCGA portal were used to determine the association with survival. Results We identified 145 metabolites, of which analysis revealed 31 differential metabolites when comparing benign and tumor tissue samples. Using the KEGG (Kyoto Encyclopedia of Genes and Genomes) Database we identified a total of 174 genes that correlated with the altered metabolic pathways involved. By integrating these genes with the transcriptomic data from the corresponding TCGA data set we identified a metabolic signature consisting of 30 genes. The signature was significant in its prediction of survival in 95 patients with a low signature score vs 282 with a high signature score (p = 0.0458). Conclusions Targeted mass spectrometry of bladder cancer is highly sensitive for detecting metabolic alterations. Applying transcriptome data allows for integration into larger data sets and identification of relevant metabolic pathways in bladder cancer progression. PMID:26802582

  3. A Systematic Review of the Diagnostic and Prognostic Value of Urinary Protein Biomarkers in Urothelial Bladder Cancer

    PubMed Central

    D’Costa, Jamie J.; Goldsmith, James C.; Wilson, Jayne S.; Bryan, Richard T.; Ward, Douglas G.

    2016-01-01

    For over 80 years, cystoscopy has remained the gold-standard for detecting tumours of the urinary bladder. Since bladder tumours have a tendency to recur and progress, many patients are subjected to repeated cystoscopies during long-term surveillance, with the procedure being both unpleasant for the patient and expensive for healthcare providers. The identification and validation of bladder tumour specific molecular markers in urine could enable tumour detection and reduce reliance on cystoscopy, and numerous classes of biomarkers have been studied. Proteins represent the most intensively studied class of biomolecule in this setting. As an aid to researchers searching for better urinary biomarkers, we report a comprehensive systematic review of the literature and a searchable database of proteins that have been investigated to date. Our objective was to classify these proteins as: 1) those with robustly characterised sensitivity and specificity for bladder cancer detection; 2) those that show potential but further investigation is required; 3) those unlikely to warrant further investigation; and 4) those investigated as prognostic markers. This work should help to prioritise certain biomarkers for rigorous validation, whilst preventing wasted effort on proteins that have shown no association whatsoever with the disease, or only modest biomarker performance despite large-scale efforts at validation. PMID:27500198

  4. Functional genomics annotation of a statistical epistasis network associated with bladder cancer susceptibility

    PubMed Central

    2014-01-01

    Background Several different genetic and environmental factors have been identified as independent risk factors for bladder cancer in population-based studies. Recent studies have turned to understanding the role of gene-gene and gene-environment interactions in determining risk. We previously developed the bioinformatics framework of statistical epistasis networks (SEN) to characterize the global structure of interacting genetic factors associated with a particular disease or clinical outcome. By applying SEN to a population-based study of bladder cancer among Caucasians in New Hampshire, we were able to identify a set of connected genetic factors with strong and significant interaction effects on bladder cancer susceptibility. Findings To support our statistical findings using networks, in the present study, we performed pathway enrichment analyses on the set of genes identified using SEN, and found that they are associated with the carcinogen benzo[a]pyrene, a component of tobacco smoke. We further carried out an mRNA expression microarray experiment to validate statistical genetic interactions, and to determine if the set of genes identified in the SEN were differentially expressed in a normal bladder cell line and a bladder cancer cell line in the presence or absence of benzo[a]pyrene. Significant nonrandom sets of genes from the SEN were found to be differentially expressed in response to benzo[a]pyrene in both the normal bladder cells and the bladder cancer cells. In addition, the patterns of gene expression were significantly different between these two cell types. Conclusions The enrichment analyses and the gene expression microarray results support the idea that SEN analysis of bladder in population-based studies is able to identify biologically meaningful statistical patterns. These results bring us a step closer to a systems genetic approach to understanding cancer susceptibility that integrates population and laboratory-based studies. PMID:24725556

  5. Arsenic-induced bladder cancer in an animal model

    SciTech Connect

    Cohen, Samuel M. Ohnishi, Takamasa Arnold, Lora L. Le, X. Chris

    2007-08-01

    Dimethylarsinic acid (DMA{sup V}) is carcinogenic to the rat urinary bladder, but not in mice. The carcinogenic mode of action involves cytotoxicity followed by regenerative cell proliferation. Dietary DMA{sup V} does not produce urinary solids or significant alterations in urinary composition. The cytotoxicity is due to formation of a reactive metabolite, likely dimethylarsinous acid (DMA{sup III}), concentrated and excreted in the urine. Urinary concentrations of DMA{sup III} are dose-dependent, and the urinary concentrations are at cytotoxic levels based on in vitro studies. The no observed effect level (NOEL) in these rat dietary studies for detectable levels of DMA{sup III}, cytotoxicity, and proliferation is 2 ppm, with marginal changes at 10 ppm. The tumorigenic dose is 100 ppm. Recent investigations have demonstrated that arsenicals administered to the rat result in binding to a specific cysteine in the hemoglobin alpha chain as DMA{sup III}, regardless of the arsenical being administered. Monomethylarsonic acid (MMA{sup V}) is not carcinogenic in rats or mice. In short term experiments ({<=} 10 weeks), sodium arsenate in the drinking water induces significant cytotoxicity and regenerative proliferation. There is little evidence that the cytotoxicity produced following administration of arsenicals is caused by oxidative damage, as antioxidants show little inhibitory activity of the cytotoxicity of the various arsenicals either in vitro or in vivo. In summary, the mode of action for DMA{sup V}-induced bladder carcinogenesis in the rat involves generation of a reactive metabolite (DMA{sup III}) leading to cytotoxicity and regenerative proliferation, is a non-linear process, and likely involves a threshold. Extrapolation to human risk needs to take this into account along with the significant differences in toxicokinetics and toxicodynamics that occur between different species.

  6. Allyl isothiocyanate-rich mustard seed powder inhibits bladder cancer growth and muscle invasion.

    PubMed

    Bhattacharya, Arup; Li, Yun; Wade, Kristina L; Paonessa, Joseph D; Fahey, Jed W; Zhang, Yuesheng

    2010-12-01

    Allyl isothiocyanate (AITC), which occurs in many common cruciferous vegetables, was recently shown to be selectively delivered to bladder cancer tissues through urinary excretion and to inhibit bladder cancer development in rats. The present investigation was designed to test the hypothesis that AITC-containing cruciferous vegetables also inhibit bladder cancer development. We focused on an AITC-rich mustard seed powder (MSP-1). AITC was stably stored as its glucosinolate precursor (sinigrin) in MSP-1. Upon addition of water, however, sinigrin was readily hydrolyzed by the accompanying endogenous myrosinase. This myrosinase was also required for full conversion of sinigrin to AITC in vivo, but the matrix of MSP-1 had no effect on AITC bioavailability. Sinigrin itself was not bioactive, whereas hydrated MSP-1 caused apoptosis and G(2)/M phase arrest in bladder cancer cell lines in vitro. Comparison between hydrated MSP-1 and pure sinigrin with added myrosinase suggested that the anticancer effect of MSP-1 was derived principally, if not entirely, from the AITC generated from sinigrin. In an orthotopic rat bladder cancer model, oral MSP-1 at 71.5 mg/kg (sinigrin dose of 9 μmol/kg) inhibited bladder cancer growth by 34.5% (P < 0.05) and blocked muscle invasion by 100%. Moreover, the anticancer activity was associated with significant modulation of key cancer therapeutic targets, including vascular endothelial growth factor, cyclin B1 and caspase 3. On an equimolar basis, the anticancer activity of AITC delivered as MSP-1 appears to be more robust than that of pure AITC. MSP-1 is thus an attractive delivery vehicle for AITC and it strongly inhibits bladder cancer development and progression. PMID:20889681

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

    PubMed Central

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

    2014-01-01

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

  8. Gender Disparities in Hematuria Evaluation and Bladder Cancer Diagnosis: A Population-Based Analysis

    PubMed Central

    Garg, Tullika; Pinheiro, Laura C.; Atoria, Coral L.; Donat, S. Machele; Weissman, Joel S.; Herr, Harry W.; Elkin, Elena B.

    2014-01-01

    Purpose Men are diagnosed with bladder cancer at three times the rate of women. However, women present with advanced disease and have poorer survival, suggesting delays in bladder cancer diagnosis. Hematuria is the presenting symptom in a majority of cases. Our objective was to assess gender differences in hematuria evaluation in older adults with bladder cancer. Materials and Methods Using the Surveillance, Epidemiology and End Results cancer registry linked with Medicare claims, we identified Medicare beneficiaries aged 66 years or older diagnosed with bladder cancer between 2000 and 2007 with a claim for hematuria in the year prior to diagnosis. We examined the impact of gender and demographic and clinical factors on time from initial hematuria claim to urology visit; and time from initial hematuria claim to hematuria evaluation including cystoscopy, upper urinary tract imaging, and urine cytology. Results Of 35,646 patients with a hematuria claim in the year preceding bladder cancer diagnosis, 97% had a urology visit claim. The mean time to urology visit was 27 days (range 0-377), and the time to urology visit was longer for women than for men (adjusted hazard ratio 0.9, 95% CI 0.87-0.92). Women were more likely to undergo delayed (after > 30 days) hematuria evaluation (adjusted odds ratio 1.13, 95% CI 1.07-1.21). Conclusion We observed longer time to a urology visit for women than for men presenting with hematuria. These findings may explain stage differences in bladder cancer diagnosis and inform efforts to reduce gender disparities in bladder cancer stage and outcomes. PMID:24835058

  9. Allyl isothiocyanate-rich mustard seed powder inhibits bladder cancer growth and muscle invasion.

    PubMed

    Bhattacharya, Arup; Li, Yun; Wade, Kristina L; Paonessa, Joseph D; Fahey, Jed W; Zhang, Yuesheng

    2010-12-01

    Allyl isothiocyanate (AITC), which occurs in many common cruciferous vegetables, was recently shown to be selectively delivered to bladder cancer tissues through urinary excretion and to inhibit bladder cancer development in rats. The present investigation was designed to test the hypothesis that AITC-containing cruciferous vegetables also inhibit bladder cancer development. We focused on an AITC-rich mustard seed powder (MSP-1). AITC was stably stored as its glucosinolate precursor (sinigrin) in MSP-1. Upon addition of water, however, sinigrin was readily hydrolyzed by the accompanying endogenous myrosinase. This myrosinase was also required for full conversion of sinigrin to AITC in vivo, but the matrix of MSP-1 had no effect on AITC bioavailability. Sinigrin itself was not bioactive, whereas hydrated MSP-1 caused apoptosis and G(2)/M phase arrest in bladder cancer cell lines in vitro. Comparison between hydrated MSP-1 and pure sinigrin with added myrosinase suggested that the anticancer effect of MSP-1 was derived principally, if not entirely, from the AITC generated from sinigrin. In an orthotopic rat bladder cancer model, oral MSP-1 at 71.5 mg/kg (sinigrin dose of 9 μmol/kg) inhibited bladder cancer growth by 34.5% (P < 0.05) and blocked muscle invasion by 100%. Moreover, the anticancer activity was associated with significant modulation of key cancer therapeutic targets, including vascular endothelial growth factor, cyclin B1 and caspase 3. On an equimolar basis, the anticancer activity of AITC delivered as MSP-1 appears to be more robust than that of pure AITC. MSP-1 is thus an attractive delivery vehicle for AITC and it strongly inhibits bladder cancer development and progression.

  10. Can bladder adenocarcinomas be distinguished from schistosomiasis-associated bladder cancers by using array comparative genomic hybridization analysis?

    PubMed

    Vauhkonen, Hanna; Böhling, Tom; Eissa, Saad; Shoman, Sohair; Knuutila, Sakari

    2007-09-01

    Bladder cancer is the most common malignancy in many tropical and subtropical areas, correlating well with the endemicity of schistostomiasis. The majority of schistostomiasis-associated (SA) bladder cancers are squamous cell cancers, whereas the majority of non-SA cases in the Western world are transitional cell cancers, suggesting different carcinogenetic mechanisms. Approximately 6% of SA and 1% of non-SA cases are adenocarcinomas. To achieve fine-resolution information of DNA copy number changes in SA adenocarcinomas, 10 tumor samples were analyzed on an oligonucleotide-based CGH array. The frequency of aberrations ranged from 2 to 17, with an average of 10 alterations per sample. The most frequently gained regions were 20q and 8q (in 70 and 60% of the cases, respectively), whereas the most frequently lost regions were 5q and 8p (both in 40% of the cases). In addition, six regions of amplification were found in three samples, containing both well characterized and novel regions. Comparison of the DNA copy number profiles to previously reported profiles of SA transitional cell carcinoma and squamous cell carcinoma revealed similarities (e.g., gains at 5p and 8q), as well as differences (e.g., TCC- and SCC-associated losses at 18p and 20p, and adenocarcinoma-associated gains at 20q). The results suggest that although SA cancers share genetic features, there also exist histology-specific regions of gain and loss. PMID:17854674

  11. Bladder cancer mortality and private well use in New England: an ecological study

    PubMed Central

    Ayotte, Joseph D; Baris, Dalsu; Cantor, Kenneth P; Colt, Joanne; Robinson, Gilpin R; Lubin, Jay H; Karagas, Margaret; Hoover, Robert N; Fraumeni, Joseph F; Silverman, Debra T

    2006-01-01

    Study objective To investigate the possible relation between bladder cancer mortality among white men and women and private water use in New England, USA, where rates have been persistently raised and use of private water supplies (wells) common. Design Ecological study relating age adjusted cancer mortality rates for white men and women during 1985–1999 and proportion of persons using private water supplies in 1970. After regressing mortality rates on population density, Pearson correlation coefficients were computed between residual rates and the proportion of the population using private water supplies, using the state economic area as the unit of calculation. Calculations were conducted within each of 10 US regions. Setting The 504 state economic areas of the contiguous United States. Participants Mortality analysis of 11 cancer sites, with the focus on bladder cancer. Main results After adjusting for the effect of population density, there was a statistically significant positive correlation between residual bladder cancer mortality rates and private water supply use among both men and women in New England (men, r = 0.42; women, r = 0.48) and New York/New Jersey (men, r = 0.49; women, r = 0.62). Conclusions Use of well water from private sources, or a close correlate, may be an explanatory variable for the excess bladder cancer mortality in New England. Analytical studies are underway to clarify the relation between suspected water contaminants, particularly arsenic, and raised bladder cancer rates in northern New England. PMID:16415269

  12. Bladder cancer mortality and private well use in New England: An ecological study

    USGS Publications Warehouse

    Ayotte, J.D.; Baris, D.; Cantor, K.P.; Colt, J.; Robinson, G.R.; Lubin, J.H.; Karagas, M.; Hoover, R.N.; Fraumeni, J.F.; Silverman, D.T.

    2006-01-01

    Study objective: To investigate the possible relation between bladder cancer mortality among white men and women and private water use in New England, USA, where rates have been persistently raised and use of private water supplies (wells) common. Design: Ecological study relating age adjusted cancer mortality rates for white men and women during 1985-1999 and proportion of persons using private water supplies in 1970. After regressing mortality rates on population density, Pearson correlation coefficients were computed between residual rates and the proportion of the population using private water supplies, using the state economic area as the unit of calculation. Calculations were conducted within each of 10 US regions. Setting: The 504 state economic areas of the contiguous United States. Participants: Mortality analysis of 11 cancer sites, with the focus on bladder cancer. Main results: After adjusting for the effect of population density, there was a statistically significant positive correlation between residual bladder cancer mortality rates and private water supply use among both men and women in New England (men, r=0.42; women, r=0.48) and New York/New Jersey (men, r=0.49; women, r=0.62). Conclusions: Use of well water from private sources, or a close correlate, may be an explanatory variable for the excess bladder cancer mortality in New England. Analytical studies are underway to clarify the relation between suspected water contaminants, particularly arsenic, and raised bladder cancer rates in northern New England.

  13. High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

    PubMed Central

    2009-01-01

    Background Egr-1 (early growth response-1 transcription factor) has been proposed to be involved in invasion and metastasis processes of human bladder cancer, but Egr-1 protein expression levels in human bladder cancer have not been investigated. In the present study we investigated the expression levels of Egr-1 protein in early stages of human bladder cancer and correlated it to later progression. Methods Expression of Egr-1 protein in human bladder cancer was examined by immunohistochemistry, on a tissue microarray constructed from tumors from 289 patients with non-muscle invasive urothelial bladder cancer. Results The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling were found to localize at the tumor front in some of the tumor biopsies. Conclusion The results from this study support a potential involvement of Egr-1 in the progression from non-muscle invasive bladder cancers to muscle invasive bladder cancer. PMID:19878561

  14. A Decade of FGF Receptor Research in Bladder Cancer: Past, Present, and Future Challenges

    PubMed Central

    di Martino, Erica; Tomlinson, Darren C.; Knowles, Margaret A.

    2012-01-01

    Fibroblast growth factors (FGFs) orchestrate a variety of cellular functions by binding to their transmembrane tyrosine-kinase receptors (FGFRs) and activating downstream signalling pathways, including RAS/MAPK, PLCγ1, PI3K, and STATs. In the last ten years, it has become clear that FGF signalling is altered in a high proportion of bladder tumours. Activating mutations and/or overexpression of FGFR3 are common in urothelial tumours with low malignant potential and low-stage and -grade urothelial carcinomas (UCs) and are associated with a lower risk of progression and better survival in some subgroups. FGFR1 is not mutated in UC, but overexpression is frequent in all grades and stages and recent data indicate a role in urothelial epithelial-mesenchymal transition. In vitro and in vivo studies have shown that FGFR inhibition has cytotoxic and/or cytostatic effects in FGFR-dependent bladder cancer cells and FGFR-targeted agents are currently being investigated in clinical studies for the treatment of UC. Urine-based tests detecting common FGFR3 mutations are also under development for surveillance of low-grade and -stage tumours and for general population screening. Overall, FGFRs hold promise as therapeutic targets, diagnostic and prognostic markers, and screening tools for early detection and clinical management of UC. PMID:22899908

  15. Detection of estrogen receptors in the trigonum and urinary bladder with an immunohistochemical technique.

    PubMed

    Bussolati, G; Tizzani, A; Casetta, G; Cassoni, P; Pacchioni, D; Piana, P; Revelli, A; Massobrio, M

    1990-09-01

    In order to detect estrogen receptors (ER) in the female bladder, 5 premenopausal and 10 postmenopausal women affected by gynecological diseases were submitted to cystoscopy, during which both the trigonum and the bladder lateral wall were biopsied. A new, simple, cost-effective immunohistochemical technique was employed to stain the estrogen specific binding sites. ER were found in the trigonum of 3 premenopausal and 4 postmenopausal subjects, while the bladder lateral wall was always ER-negative. A comparison with previously used ER detection methods and a discussion of further hypothetical applications of the immunohistochemical technique in the study of the lower female urogenital tract are reported.

  16. Metastatic cancer of the urinary bladder: can it be a nonnatural death?

    PubMed

    Dolinak, David

    2007-09-01

    Deaths from metastatic carcinoma are almost exclusively viewed as wholly natural deaths. However, if it can be shown that a cancer has arisen as a result of a prior traumatic injury and the body's healing response to the injury, or treatment thereof, then in select cases, the manner of death shall reflect that of the precipitating injury. This case report is that of a woman who was rendered quadriplegic from spinal cord injury sustained in a motor vehicle crash when she was 22 years old. She died at the age of 49 years from widely metastatic squamous cell carcinoma of the urinary bladder. Her bladder cancer most likely arose from decades-long chronic irritation of the bladder epithelium by physical contact with an indwelling Foley catheter and urinary infections. Over the years, the chronic bladder irritation likely precipitated metaplastic, dysplastic, and finally neoplastic changes of the bladder epithelium, providing a link between her spinal cord injury, the indwelling Foley catheter, and her bladder cancer, engendering an accidental manner of death. The manner of death reflected the circumstances of her injury that predisposed her to the cancer that eventually caused her death.

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

    PubMed

    Anderson-Otunu, Oghenetejiri; Akhtar, Saeed

    2016-01-01

    Literature on the relationship between recurrent urinary tract infections and urinary bladder carcinoma risk has been inconsistent. Therefore, we carried out this systematic review of observational studies to ascertain if there is any association between chronic urinary tract infection and urinary bladder carcinoma. A total of 10 databases were searched using Boolean: CINAHL, PUBMED, Google Scholar, Medline, Science Direct, SCIRUS, Cochrane, UK PubMed central, NHS evidence and WHO-website. The search yielded an initial hit of 3,518 articles and after screening and critical appraisal, seven studies were included for this review. Four articles reported an association between chronic urinary tract infections and bladder cancer while three concluded a weak or no association at least in one gender. Main findings in this review were that most of the studies reported an association between chronic urinary tract infections and bladder cancer risk. However, inferences about the causal association between chronic urinary tract infections and bladder cancer risk should be drawn cautiously considering the methodological limitations of case-control studies included in this review. Therefore, more empirical evidence is needed to determine the causal nature of relationships between chronic urinary tract infections and bladder cancer risk. PMID:27644620

  18. Assessment criteria for compensation of occupational bladder cancer.

    PubMed

    Schops, Wolfgang; Jungmann, Olaf; Zumbe, Jurgen; Zellner, Michael; Hengstler, Jan G; Golka, Klaus

    2013-01-01

    In Germany, more than 100 bladder tumor cases are annually recognized as occupational disease and compensated, given that medical experts regard exposure to carcinogenic aromatic amines as a likely cause of cancer. The amount of compensation is initially based on the tumor staging and grading at the time of initial diagnosis ("basic MdE") (MdE--reduction of earning capacity) and is adapted after a recurrence-free period of 2 and 5 years, respectively. In the event of treatment or tumor-related secondary conditions, the monthly compensation increases based on the severity of the objectified functional disorder. In the following article, medical experts specializing in this field provide a complete list of all known disorders, including treatment-related loss of a kidney or erectile dysfunction. In addition, the weighting of medical criteria in the assessment and calculation of the compensation is analyzed in greater detail. Since the given criteria are based on comprehensible experiences of urologists with their patients, they also provide medical experts in other countries with valuable points of reference for the calculation of the compensation.

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2015-12-01

    The International Agency for Research on Cancer has classified diesel exhaust as a carcinogen based on lung cancer evidence; however, few studies have investigated the effect of engine emissions on bladder cancer. The purpose of this study was to investigate the association between occupational exposure to diesel and gasoline emissions and bladder cancer in men using data from the Canadian National Enhanced Cancer Surveillance System; a population-based case-control study. This analysis included 658 bladder cancer cases and 1360 controls with information on lifetime occupational histories and a large number of possible cancer risk factors. A job-exposure matrix for engine emissions was supplemented by expert review to assign values for each job across three dimensions of exposure: concentration, frequency, and reliability. Odds ratios (OR) and their corresponding 95% confidence intervals were estimated using logistic regression. Relative to unexposed, men ever exposed to high concentrations of diesel emissions were at an increased risk of bladder cancer (OR = 1.64, 0.87-3.08), but this result was not significant, and those with >10 years of exposure to diesel emissions at high concentrations had a greater than twofold increase in risk (OR = 2.45, 1.04-5.74). Increased risk of bladder cancer was also observed with >30% of work time exposed to gasoline engine emissions (OR = 1.59, 1.04-2.43) relative to the unexposed, but only among men that had never been exposed to diesel emissions. Taken together, our findings support the hypothesis that exposure to high concentrations of diesel engine emissions may increase the risk of bladder cancer. PMID:26511593

  1. Genetic variants in miRNAs predict bladder cancer risk and recurrence.

    PubMed

    Wang, Meilin; Chu, Haiyan; Li, Pu; Yuan, Lin; Fu, Guangbo; Ma, Lan; Shi, Danni; Zhong, Dongyan; Tong, Na; Qin, Chao; Yin, Changjun; Zhang, Zhengdong

    2012-12-01

    miRNAs play important roles in numerous cellular processes, including development, proliferation, apoptosis, and carcinogenesis. Because altered expression and function of miRNAs has been observed in bladder cancer, we investigated whether genetic variations in miRNAs are associated with bladder cancer risk and prognosis. Using bioinformatics tools, we selected five single-nucleotide polymorphisms located in miRNAs and used these to evaluate miRNA-disease associations in a two-stage model, consisting of 1,019 bladder cancer cases and 1,182 controls (683 cases and 728 controls in the training set and 336 cases and 454 controls in the test set). We found that miR-146a rs2910164 C allele was associated with significantly decreased risk of bladder cancer in both the training and test sets, as well as the combined set [OR = 0.80, 95% confidence interval (CI) = 0.71-0.90, P = 2.92 × 10(-4)]. Furthermore, the rs2910164 GC/CC genotypes conferred a significantly reduced risk of recurrence, compared with the GG genotype (P = 0.016). Functional analysis revealed that miR-146a rs2910164 C allele inhibited cell proliferation and significantly downregulated expression of IRAK1 and TRAF6 in bladder cancer cells. Additional examination of 64 bladder cancer tissues showed that individuals carrying the C allele had increased expression levels of miR-146a compared with those carrying the G allele (P = 0.010). Taken together, our findings show that miR-146a rs2910164 plays an important role in the risk and recurrence of bladder cancer, suggesting it may represent a biomarker for risk prevention and therapeutic intervention. Further larger and prospective cohorts are needed to validate our findings.

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

    PubMed

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

    2015-04-01

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

  3. Breast Cancer Detection

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The BioScan System was developed by OmniCorder Technologies, Inc. at the Jet Propulsion Laboratory. The system is able to locate cancerous lesions by detecting the cancer's ability to recruit a new blood supply. A digital sensor detects infrared energy emitted from the body and identifies the minute differences accompanying the blood flow changes associated with cancerous cells. It also has potential use as a monitoring device during cancer treatment. This technology will reduce the time taken to detect cancerous cells and allow for earlier intervention, therefore increasing the overall survival rates of breast cancer patients.

  4. The metabolic profiles of pterin compounds as potential biomarkers of bladder cancer-Integration of analytical-based approach with biostatistical methodology.

    PubMed

    Kośliński, Piotr; Daghir-Wojtkowiak, Emilia; Szatkowska-Wandas, Paulina; Markuszewski, Marcin; Markuszewski, Michał J

    2016-08-01

    Cancer disease is the second leading cause of death across the world. The analysis of potential biomarkers of cancer can be useful in cancer screening or cancer diagnosis, and may provide valuable information on the disease risk and progression. Pterin compounds have been studied as candidates of potential biomarkers as their elevated levels have been reported in various cancer diseases. The objective of the study was to compare the profiles of six pterin compounds in urine of 35 healthy subjects and 46 patients diagnosed of bladder cancer with the use of HPLC coupled with fluorimetric detection. The results of the chromatographic analysis together with biostatistical-based approach showed, that the concentrations of pterin compounds in bladder cancer patients were higher as compared to healthy individuals, and statistically significant differences between patients and controls were reported for xanthopterin and isoxanthopterin. Moreover, gender-specific analysis revealed, that the concentrations of pterins in the group of women reached higher values in comparison to men. For metabolites juxtaposed in pairs, namely xanthopterin and isoxanthopterin as well as for neopterin and biopterin, we found significant positive correlations in the group of both, patients and healthy individuals. We therefore conclude, that chromatographic analysis with simultaneous extensive biostatistical-based interpretation of the metabolite profiles may provide deeper understanding of the relationships between pterin metabolites. The results do not prejudge the possibility of using pterin compounds in the diagnosis of bladder tumors. However the results may have an impact on the study of bladder cancer biomarkers.

  5. Identification of extracellular vesicle-borne periostin as a feature of muscle-invasive bladder cancer

    PubMed Central

    Silvers, Christopher R.; Liu, Yu-Ru; Wu, Chia-Hao; Miyamoto, Hiroshi; Messing, Edward M.; Lee, Yi-Fen

    2016-01-01

    Muscle-invasive bladder cancer (MIBC) is an aggressive malignancy with high mortality, and heterogeneity in MIBC results in variable clinical outcomes, posing challenges for clinical management. Extracellular vesicles (EVs) derived from MIBC have been shown to promote cancer progression. EVs derived from bladder cell lines were subjected to proteomic analysis, and periostin was chosen for further characterization due to its stage-specific gene expression profile. Knockdown of periostin by RNA interference reduces invasiveness in vitro and produces a rounder morphology. Importantly, treating low grade BC cells with periostin-rich EVs promotes cell aggressiveness and activates ERK oncogenic signals, and periostin suppression reverses these effects. These data suggest that MIBC might transfer periostin in an EV-mediated paracrine manner to promote the disease. To determine the potential of periostin as a bladder cancer indicator, patient urinary EVs were examined and found to have markedly higher levels of periostin than controls. In addition, immunohistochemical staining of a bladder cancer tissue microarray revealed that the presence of periostin in MIBC cells is correlated with worse prognosis. In conclusion, periostin is a component of bladder cancer cells associated with poor clinical outcome, and EVs can transfer oncogenic molecules such as periostin to affect the tumor environment and promote cancer progression. PMID:26981774

  6. miR-451 suppresses bladder cancer cell migration and invasion via directly targeting c-Myc.

    PubMed

    Wang, Jun; Zhao, Xiaomei; Shi, Jianhua; Pan, Yiwei; Chen, Qinghai; Leng, Pengfei; Wang, Yan

    2016-10-01

    MicroRNA (miRNA) expression is shown dysregulated in tumors. It has been reported that miR-451 alters gene expression and regulates tumorigenesis in various cancer tissues. However, its underlying biological significance in bladder cancer remains to be clarified. In the present study, we investigated the function and molecular mechanism of miR-451 involved in bladder cancer cell migration and invasion. Our results showed that miR-451 was downregulated in clinical bladder carcinoma tissues compared with adjacent bladder tissues. Overexpression of miR-451 significantly retarded the proliferation, migration and invasion of bladder cancer T24 and 5637 cells in vitro. Moreover, the attenuated cell migration and invasion by miR-451 was correlated with increased apoptosis. However, our dual-luciferase reporter assay validated that c-Myc, an oncogene in many tumors, was a direct target gene of miR-451 in bladder cancer. The expression of c-Myc was repressed by miR-451 in bladder cancer cells, and knockdown of c-Myc mimicked the effects of miR-451 overexpression. This discovery suggested that miR-451 is a tumor suppressor modulating bladder cancer cell migration and invasion by directly targeting c-Myc. In addition, apoptosis promoted by miR-451 may participates in this biological behavior. Therefore, target miR-451 may be a novel therapeutic intervention for bladder cancer. PMID:27571748

  7. Urothelial cancer of the urinary bladder: can lessons learned be applied to the upper urinary tract?

    PubMed

    Krabbe, Laura M; Hutchinson, Ryan C; Margulis, Vitaly

    2016-08-01

    Even though urothelial cancer may occur anywhere in the urinary tract, it is most commonly found in the urinary bladder. Due to its higher incidence, this disease is studied in the bladder much more frequently than in the upper urinary tract. The question that arises is, to what extent can concepts and treatment paradigms derived from lower tract disease be applied to urothelial carcinoma of the upper urinary tract? This review aims at providing an overview of established care concepts in urothelial carcinoma of the bladder and applicability of these findings to tumors of the upper urinary tract.

  8. The role of radiotherapy in the treatment of muscle invasive bladder cancer

    SciTech Connect

    Porter, A.T. )

    1990-01-01

    The treatment of muscle invasive bladder cancer still remains controversial. It is becoming more clear, however, that attempts to retain the functional capacity of the urinary bladder by the use of non-surgical methods may be of benefit in the long-term. Studies using radiotherapy in combination with chemotherapeutic agents or intravesicle sensitizers, or the use of radiotherapy alone, but optimized (i.e., brachytherapy and altered fractionation) may be able to achieve improved local control while retaining a functional bladder. Attempts to couple this with improved survival due to the sterilization of occult metastases is still subject to much debate.51 references.

  9. [Application of radiofrequency hyperthermia for treating advanced urinary bladder cancer--a case report].

    PubMed

    Kubota, Y; Takebayashi, S; Asakura, K; Oshima, H

    1984-02-01

    A patient with advanced urinary bladder cancer treated with a combination of radiation and hyperthermia, using short-wave radiofrequency (RF) and intravesical irrigation with warm water is reported. The tumor temperature was successfully maintained at 43 degrees to 44.6 degrees by external application of 13.56 MHZ RF when the bladder was irrigated with heated saline (intravesical temperature: 43 degrees) Hyperthermia was performed for 30 min immediately after each course of external bladder irradiation (Linac: 400 rad, twice a week; total 5 weeks exposure of 4000 rad). The tumor disappeared completely (CR) after the completion of the combination therapy. PMID:6200623

  10. Prostate and Urologic Cancer | Division of Cancer Prevention

    Cancer.gov

    Conducts and supports research on the prevention and early detection of prostate and bladder cancer. | Conducts and supports research on the prevention and early detection of prostate, bladder, and skin cancers.

  11. Common genetic variants in the PSCA gene influence gene expression and bladder cancer risk

    PubMed Central

    Fu, Yi-Ping; Kohaar, Indu; Rothman, Nathaniel; Earl, Julie; Figueroa, Jonine D.; Ye, Yuanqing; Malats, Núria; Tang, Wei; Liu, Luyang; Garcia-Closas, Montserrat; Muchmore, Brian; Chatterjee, Nilanjan; Tarway, McAnthony; Kogevinas, Manolis; Porter-Gill, Patricia; Baris, Dalsu; Mumy, Adam; Albanes, Demetrius; Purdue, Mark P.; Hutchinson, Amy; Carrato, Alfredo; Tardón, Adonina; Serra, Consol; García-Closas, Reina; Lloreta, Josep; Johnson, Alison; Schwenn, Molly; Karagas, Margaret R.; Schned, Alan; Diver, W. Ryan; Gapstur, Susan M.; Thun, Michael J.; Virtamo, Jarmo; Chanock, Stephen J.; Fraumeni, Joseph F.; Silverman, Debra T.; Wu, Xifeng; Real, Francisco X.; Prokunina-Olsson, Ludmila

    2012-01-01

    Genome-wide association studies have identified a SNP, rs2294008, on 8q24.3 within the prostate stem cell antigen (PSCA) gene, as a risk factor for bladder cancer. To fine-map this region, we imputed 642 SNPs within 100 Kb of rs2294008 in addition to 33 markers genotyped in one of the reported genome-wide association study in 8,652 subjects. A multivariable logistic regression model adjusted for rs2294008 revealed a unique signal, rs2978974 (r2 = 0.02, D′ = 0.19 with rs2294008). In the combined analysis of 5,393 cases and 7,324 controls, we detected a per-allele odds ratio (OR) = 1.11 [95% confidence interval (CI) = 1.06–1.17, P = 5.8 × 10−5] for rs2294008 and OR = 1.07 (95% CI = 1.02–1.13, P = 9.7 × 10−3) for rs2978974. The effect was stronger in carriers of both risk variants (OR = 1.24, 95% CI = 1.08–1.41, P = 1.8 × 10−3) and there was a significant multiplicative interaction (P = 0.035) between these two SNPs, which requires replication in future studies. The T risk allele of rs2294008 was associated with increased PSCA mRNA expression in two sets of bladder tumor samples (n = 36, P = 0.0007 and n = 34, P = 0.0054) and in normal bladder samples (n = 35, P = 0.0155), but rs2978974 was not associated with PSCA expression. SNP rs2978974 is located 10 Kb upstream of rs2294008, within an alternative untranslated first exon of PSCA. The non-risk allele G of rs2978974 showed strong interaction with nuclear proteins from five cell lines tested, implying a regulatory function. In conclusion, a joint effect of two PSCA SNPs, rs2294008 and rs2978974, suggests that both variants may be important for bladder cancer susceptibility, possibly through different mechanisms that influence the control of mRNA expression and interaction with regulatory factors. PMID:22416122

  12. Real time diagnosis of bladder cancer with probe-based confocal laser endomicroscopy

    NASA Astrophysics Data System (ADS)

    Liu, Jen-Jane; Wu, Katherine; Adams, Winifred; Hsiao, Shelly T.; Mach, Kathleen E.; Beck, Andrew H.; Jensen, Kristin C.; Liao, Joseph C.

    2011-02-01

    Probe-based confocal laser endomicroscopy (pCLE) is an emerging technology for in vivo optical imaging of the urinary tract. Particularly for bladder cancer, real time optical biopsy of suspected lesions will likely lead to improved management of bladder cancer. With pCLE, micron scale resolution is achieved with sterilizable imaging probes (1.4 or 2.6 mm diameter), which are compatible with standard cystoscopes and resectoscopes. Based on our initial experience to date (n = 66 patients), we have demonstrated the safety profile of intravesical fluorescein administration and established objective diagnostic criteria to differentiate between normal, benign, and neoplastic urothelium. Confocal images of normal bladder showed organized layers of umbrella cells, intermediate cells, and lamina propria. Low grade bladder cancer is characterized by densely packed monomorphic cells with central fibrovascular cores, whereas high grade cancer consists of highly disorganized microarchitecture and pleomorphic cells with indistinct cell borders. Currently, we are conducting a diagnostic accuracy study of pCLE for bladder cancer diagnosis. Patients scheduled to undergo transurethral resection of bladder tumor are recruited. Patients undergo first white light cystocopy (WLC), followed by pCLE, and finally histologic confirmation of the resected tissues. The diagnostic accuracy is determined both in real time by the operative surgeon and offline after additional image processing. Using histology as the standard, the sensitivity, specificity, positive and negative predictive value of WLC and WLC + pCLE are calculated. With additional validation, pCLE may prove to be a valuable adjunct to WLC for real time diagnosis of bladder cancer.

  13. The route to personalized medicine in bladder cancer: where do we stand?

    PubMed

    Massari, Francesco; Ciccarese, Chiara; Santoni, Matteo; Brunelli, Matteo; Conti, Alessandro; Modena, Alessandra; Montironi, Rodolfo; Santini, Daniele; Cheng, Liang; Martignoni, Guido; Cascinu, Stefano; Tortora, Giampaolo

    2015-09-01

    Recent advances in molecular biology and drug design have described novel targets in bladder cancer. EGFR, fibroblast growth factor receptor (FGFR), VEGFR, phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, PD-1, cyclooxygenase 2 (COX-2), Aurora kinase A, and miRNA are just examples of these opening frontiers. In addition, epithelial to mesenchymal transition (EMT) and cancer stem cells (CSCs) are promising candidates for future therapeutic approaches. Novel agents, combination, and sequences are emerging from the 747 clinical studies presently in course in bladder cancer to optimize patient outcomes. This report describes the emerging targets and provides an update on ongoing phase I, II, and III trials and preliminary results on targeted agents, used alone, in sequences, or in combination for patients with bladder cancer.

  14. Noninvasive identification of bladder cancer with sub-surface backscattered light

    SciTech Connect

    Bigio, I.J.; Mourant, J.R.; Boyer, J.; Johnson, T.; Shimada, T.; Conn, R.L.

    1994-02-01

    A non-invasive diagnostic tool that could identify malignancy in situ and in real time would have a major impact on the detection and treatment of cancer. We have developed and are testing early prototypes of an optical biopsy system (OBS) for detection of cancer and other tissue pathologies. The OBS invokes a unique approach to optical diagnosis of tissue pathologies based on the elastic scattering properties, over a wide range of wavelengths, of the microscopic structure of the tissue. Absorption bands in the tissue also add useful complexity to the spectral data collected. The use of elastic scattering as the key to optical tissue diagnostics in the OBS is based on the fact that many tissue pathologies, including a majority of cancer forms, manifest significant architectural changes at the cellular and sub-cellular level. Since the cellular components that cause elastic scattering have dimensions typically on the order of visible to near-IR wavelengths, the elastic (Mie) scattering properties will be strongly wavelength dependent. Thus, morphology and size changes can be expected to cause significant changes in an optical signature that is derived from the wavelength-dependence of elastic scattering as well as absorption. The data acquisition and storage/display time with the OBS instrument is {approximately}1 second. Thus, in addition to the reduced invasiveness of this technique compared with current state-of-the-art methods (surgical biopsy and pathology analysis), the OBS offers the possibility of impressively faster diagnostic assessment. The OBS employs a small fiber-optic probe that is amenable to use with any endoscope, catheter or hypodermic, or to direct surface examination (e.g., as in skin cancer or cervical cancer). We report here specifically on its potential application in the detection of bladder cancer.

  15. Radiotherapy in muscle-invasive bladder cancer: the latest research progress and clinical application

    PubMed Central

    Zhang, Shuo; Yu, Yong-Hua; Zhang, Yong; Qu, Wei; Li, Jia

    2015-01-01

    The role of radiotherapy (RT) in the management of urinary bladder cancer has undergone several alterations along the last decades. Recently, many protocols have been developed supporting the use of multi-modality therapy, and the concept of organ preservation began to be reconsidered. Advances in radiotherapy planning, verification, and delivery provide a method to optimize radiotherapy for bladder cancer and overcome difficulties which have previously limited the success of this treatment. They offer the opportunity to enhance the therapeutic ratio by reducing the volume of normal tissue irradiated and by increasing radiation dose or using more intensive fractionation and synchronous chemotherapy regimes. These techniques have a large potential to improve the therapeutic outcome of bladder cancer. In the near future, it should be possible to offer selected patients with muscle-invasive bladder cancer an organ-sparing, yet effective combined-modality treatment. In this review, we aim to present the role of radiotherapy in the management of muscle invasive bladder cancer. Alternative methods of improving treatment accuracy such as helical tomotherapy, adaptive radiotherapy and radiochemotherapy are also discussed. PMID:25973322

  16. Sex differences in the MB49 syngeneic, murine model of bladder cancer

    PubMed Central

    White-Gilbertson, Shai; Davis, Megan; Voelkel-Johnson, Christina; Kasman, Laura M.

    2016-01-01

    OBJECTIVE The MB49 syngeneic, murine model of bladder cancer has been widely used for more than 35 years. In humans, bladder cancer is one third as prevalent in women as in men, with a trend toward lower prevalence in parous compared to nulliparous women. Our objective was to determine if the MB49 bladder cancer model reproduces the sex differences observed in humans, and to determine its sensitivity to testosterone and the pregnancy hormone, human chorionic gonadotropin (hCG). METHODS Male and female C57BL/6 mice were implanted with MB49 murine bladder cancer cells, and observed for tumor growth. MB49 dose responses to hCG and dihydrotestosterone were determined in vitro. RESULTS MB49 tumor growth was significantly greater in male mice than female mice. Pregnancy did not affect MB49 tumor growth in female mice. MB49 cells did not proliferate in response to hCG in vitro and the functional receptor for gonadotropins was absent. Dihydrotestosterone strongly stimulated growth of MB49 cells in vitro. CONCLUSIONS The MB49 murine model of bladder cancer reproduced some aspects of the sex differences observed in humans. Our results suggest that testosterone may stimulate MB49 cell proliferation, which may explain the more rapid MB49 tumor growth observed in male mice. PMID:26998503

  17. Effect of various natural products on growth of bladder cancer cells: two promising mushroom extracts.

    PubMed

    Konno, Sensuke

    2007-03-01

    Despite the availability of several therapeutic options, a safer and more effective modality is urgently needed for treatment of bladder cancer. Specific immunotherapy is effective, but severe side effects limit its clinical use and underscore the need for unconventional therapies using less toxic substances. Many natural substances are touted for their medicinal aspects and side effect profiles, and some of these have been well characterized for their biological and medicinal properties. Accordingly, the effects on bladder cancer cells in vitro were investigated. Eight commercially available natural products were tested for possible effects on the growth of human bladder cancer T24 cells. This study demonstrated that two mushroom extracts, GD- and PL-fractions, induced a significant (>90 percent) growth reduction in 72 hours, whereas the remaining six products had no effect. Interestingly, non-toxic concentrations of the GD- or PL-fractions, when combined with a non-toxic concentration of vitamin C, became highly cytotoxic, resulting in >90-percent cell death. Thus, vitamin C appears to act synergistically with these fractions to potentiate their bioactivity (cytotoxicity). No other products tested demonstrated such a synergistic potentiation with vitamin C. The present study indicates that GD- and PL-fractions appear to have the most potent cytotoxic effect on human bladder cancer T24 cells. It is thus plausible that these substances could be used, solely or combined with conventional modalities, for the treatment of superficial bladder cancer.

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

    PubMed

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

    1984-05-01

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

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

    PubMed

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

    2012-01-01

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

  20. The softening of human bladder cancer cells happens at an early stage of the malignancy process.

    PubMed

    Ramos, Jorge R; Pabijan, Joanna; Garcia, Ricardo; Lekka, Malgorzata

    2014-01-01

    Various studies have demonstrated that alterations in the deformability of cancerous cells are strongly linked to the actin cytoskeleton. By using atomic force microscopy (AFM), it is possible to determine such changes in a quantitative way in order to distinguish cancerous from non-malignant cells. In the work presented here, the elastic properties of human bladder cells were determined by means of AFM. The measurements show that non-malignant bladder HCV29 cells are stiffer (higher Young's modulus) than cancerous cells (HTB-9, HT1376, and T24 cell lines). However, independently of the histological grade of the studied bladder cancer cells, all cancerous cells possess a similar level of the deformability of about a few kilopascals, significantly lower than non-malignant cells. This underlines the diagnostic character of stiffness that can be used as a biomarker of bladder cancer. Similar stiffness levels, observed for cancerous cells, cannot be fully explained by the organization of the actin cytoskeleton since it is different in all malignant cells. Our results underline that it is neither the spatial organization of the actin filaments nor the presence of stress fibers, but the overall density and their 3D-organization in a probing volume play the dominant role in controlling the elastic response of the cancerous cell to an external force. PMID:24778971

  1. The softening of human bladder cancer cells happens at an early stage of the malignancy process

    PubMed Central

    Ramos, Jorge R; Pabijan, Joanna

    2014-01-01

    Summary Various studies have demonstrated that alterations in the deformability of cancerous cells are strongly linked to the actin cytoskeleton. By using atomic force microscopy (AFM), it is possible to determine such changes in a quantitative way in order to distinguish cancerous from non-malignant cells. In the work presented here, the elastic properties of human bladder cells were determined by means of AFM. The measurements show that non-malignant bladder HCV29 cells are stiffer (higher Young’s modulus) than cancerous cells (HTB-9, HT1376, and T24 cell lines). However, independently of the histological grade of the studied bladder cancer cells, all cancerous cells possess a similar level of the deformability of about a few kilopascals, significantly lower than non-malignant cells. This underlines the diagnostic character of stiffness that can be used as a biomarker of bladder cancer. Similar stiffness levels, observed for cancerous cells, cannot be fully explained by the organization of the actin cytoskeleton since it is different in all malignant cells. Our results underline that it is neither the spatial organization of the actin filaments nor the presence of stress fibers, but the overall density and their 3D-organization in a probing volume play the dominant role in controlling the elastic response of the cancerous cell to an external force. PMID:24778971

  2. Association Between Longer Therapy With Thiazolidinediones and Risk of Bladder Cancer: A Cohort Study

    PubMed Central

    2012-01-01

    Background The use of pioglitazone, a thiazolidinedione (TZD), may increase the risk of bladder cancer in patients with type 2 diabetes. In this study, we assessed the risk of bladder cancer associated with the use of TZDs and between pioglitazone and rosiglitazone, an alternative TZD. Methods We conducted a retrospective cohort study of patients with type 2 diabetes mellitus who initiated treatment with a TZD (n = 18 459 patients) or a sulfonylurea (SU) (n = 41 396 patients) between July 1, 2000, and August 31, 2010, using The Health Improvement Network database in the United Kingdom. Incident cancers were identified for 196 708 person-years of follow-up. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of bladder cancer in the TZD cohort compared with the SU cohort (referent), adjusted for potential confounders. Risk associated with increasing duration of drug exposure was also examined. All statistical tests were two-sided. Results We identified 60 incident bladder cancers in the TZD cohort and 137 cancers in the SU cohort. No difference in bladder cancer risk was found between the two cohorts (TZD vs SU, HR = 0.93, 95% CI = 0.68 to 1.29) in analyses that did not account for duration of exposure. However, the risk of bladder cancer was increased among patients with the longest duration of TZD vs SU therapy (≥5 years of use, HR = 3.25, 95% CI = 1.08 to 9.71) and among those with the longest time since initiation of therapy (≥5 years since first use, HR = 2.53, 95% CI = 1.12 to 5.77). Risk of bladder cancer also increased with increasing time since initiation of pioglitazone (P trend < .001) and rosiglitazone (P trend = .006). Comparison of pioglitazone to rosiglitazone use did not demonstrate difference in cancer risk (P = .49). Conclusion Long-term TZD therapy (≥5 years) in patients with type 2 diabetes may be associated with an increased risk of bladder cancer, which may be

  3. Evidence for toxicity differences between inorganic arsenite and thioarsenicals in human bladder cancer cells.

    PubMed

    Naranmandura, Hua; Ogra, Yasumitsu; Iwata, Katsuya; Lee, Jane; Suzuki, Kazuo T; Weinfeld, Michael; Le, X Chris

    2009-07-15

    Arsenic toxicity is dependent on its chemical species. In humans, the bladder is one of the primary target organs for arsenic-induced carcinogenicity. However, little is known about the mechanisms underlying arsenic-induced carcinogenicity, and what arsenic species are responsible for this carcinogenicity. The present study aimed at comparing the toxic effect of DMMTA(V) with that of inorganic arsenite (iAs(III)) on cell viability, uptake efficiency and production of reactive oxygen species (ROS) toward human bladder cancer EJ-1 cells. The results were compared with those of a previous study using human epidermoid carcinoma A431 cells. Although iAs(III) was known to be toxic to most cells, here we show that iAs(III) (LC(50)=112 microM) was much less cytotoxic than DMMTA(V) (LC(50)=16.7 microM) in human bladder EJ-1 cells. Interestingly, pentavalent sulfur-containing DMMTA(V) generated a high level of intracellular ROS in EJ-1 cells. However, this was not observed in the cells exposed to trivalent inorganic iAs(III) at their respective LC(50) dose. Furthermore, the presence of N-acetyl-cysteine completely inhibited the cytotoxicity of DMMTA(V) but not iAs(III), suggesting that production of ROS was the main cause of cell death from exposure to DMMTA(V), but not iAs(III). Because the cellular uptake of iAs(III) is mediated by aquaporin proteins, and because the resistance of cells to arsenite can be influenced by lower arsenic uptake due to lower expression of aquaporin proteins (AQP 3, 7 and 9), the expression of several members of the aquaporin family was also examined. In human bladder EJ-1 cells, mRNA/proteins of AQP3, 7 and 9 were not detected by reverse transcription polymerase chain reaction (RT-PCR)/western blotting. In A431 cells, only mRNA and protein of AQP3 were detected. The large difference in toxicity between the two cell lines could be related to their differences in uptake of arsenic species.

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

    SciTech Connect

    Li, Shiqi; Xu, Xianglai; Xu, Xin; Hu, Zhenghui; Wu, Jian; Zhu, Yi; Chen, Hong; Mao, Yeqing; Lin, Yiwei; Luo, Jindan; Zheng, Xiangyi; Xie, Liping

    2013-11-29

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

  5. Unusual appearance for urinary bladder obstruction detected with 99mTc-MDP bone scintigraphy.

    PubMed

    Wright, Chadwick L; Sharma, Akash

    2015-12-01

    Unanticipated but clinically significant nonosseous findings can be detected during routine bone scintigraphy. We present a case of an 83-year-old man who presented with a pathologic fracture of the right femur. Whole-body bone scintigraphy for osseous staging revealed intense radiotracer accumulation in the kidneys and ureters but no activity within the urinary bladder. The patient had not voided for 14 hours. A Foley catheter was inserted, and more than 2000 mL of urine was drained, most consistent with urinary bladder obstruction. Subsequent repeat images demonstrated marked reduction of the renal and ureteral activity with trace activity in the urinary bladder.

  6. Bladder cancer screening program for a petrochemical cohort with potential exposure to beta-napthylamine.

    PubMed

    Felknor, Sarah A; Delclos, George L; Lerner, Seth P; Burau, Keith D; Wood, Susan M; Lusk, Christine M; Jalayer, Annette D

    2003-03-01

    Approximately 1800 workers in pipe manufacturing plants in the United States may have been exposed to beta-napthlyamnine between 1970 and 1996. Once the chemical was detected, the contaminated additive in the resin was identified and discontinued. A bladder cancer-screening program was initiated in 1999. An annual two-stage screening program was developed to test for microscopic hematuria (stage one) and cytology (stage two), with a urology referral of positive or suspicious cytology. This paper presents the program methodology, cohort enumeration, recruitment, and enrollment strategies, and screening protocol. Enrollment data from the first 3 years are presented. Annual screening of a cohort of current and former employees is feasible. Original personnel records are often incomplete, making cohort identification important. Personal contact and follow-up are key elements of successful recruitment and retention.

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

    PubMed

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

    2015-11-01

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

  8. Hypermethylation of p16 and DAPK promoter gene regions in patients with non-invasive urinary bladder cancer

    PubMed Central

    Jabłonowski, Zbigniew; Reszka, Edyta; Gromadzińska, Jolanta; Wąsowicz, Wojciech; Sosnowski, Marek

    2011-01-01

    Introduction The aim of the study was to examine the frequency of methylation status in promoter regions of p16 and DAPK genes in patients with non-invasive bladder cancer. Material and methods Forty-two patients (92.9% men, 73.8% smokers, 71.4% T1G1, 19.1% T1G2, 9.5% T1G3) and 36 healthy controls were studied. Isolation of genomic DNA from blood serum and methylation-specific PCR (MSP) were applied. Methylation status – methylated and unmethylated promoter regions of p16 and DAPK genes were analysed. Results Seventeen out of 42 patients (40.5%) had the methylated p16 gene, while methylation of the DAPK gene was seen in 27 of 42 cases (64.3%). In 12 patients (28.6%) both analysed genes were methylated. A statistically significant (p = 0.046) higher frequency of DAPK gene methylation (71.4%) was observed in patients with lower grade (G1) bladder cancer. Conclusions Detection of the aberrant hypermethylation of DAPK and p16 genes in blood DNA from non-invasive bladder cancer patients might offer an effective means for earlier auxiliary diagnosis of the malignancy. PMID:22295037

  9. Microwave Radiometry for Non-Invasive Detection of Vesicoureteral Reflux (VUR) Following Bladder Warming.

    PubMed

    Stauffer, Paul R; Maccarini, Paolo F; Arunachalam, Kavitha; De Luca, Valeria; Salahi, Sara; Boico, Alina; Klemetsen, Oystein; Birkelund, Yngve; Jacobsen, Svein K; Bardati, Fernando; Tognolatti, Piero; Snow, Brent

    2011-01-01

    BACKGROUND: Vesicoureteral reflux (VUR) is a serious health problem leading to renal scarring in children. Current VUR detection involves traumatic x-ray imaging of kidneys following injection of contrast agent into bladder via invasive Foley catheter. We present an alternative non-invasive approach for detecting VUR by radiometric monitoring of kidney temperature while gently warming the bladder. METHODS: We report the design and testing of: i) 915MHz square slot antenna array for heating bladder, ii) EMI-shielded log spiral microstrip receive antenna, iii) high-sensitivity 1.375GHz total power radiometer, iv) power modulation approach to increase urine temperature relative to overlying perfused tissues, and v) invivo porcine experiments characterizing bladder heating and radiometric temperature of aaline filled 30mL balloon "kidney" implanted 3-4cm deep in thorax and varied 2-6°C from core temperature. RESULTS: SAR distributions are presented for two novel antennas designed to heat bladder and monitor deep kidney temperatures radiometrically. We demonstrate the ability to heat 180mL saline in in vivo porcine bladder to 40-44°C while maintaining overlying tissues <38°C using time-modulated square slot antennas coupled to the abdomen with room temperature water pad. Pathologic evaluations confirmed lack of acute thermal damage in pelvic tissues for up to three 20min bladder heat exposures. The radiometer clearly recorded 2-6°C changes of 30mL "kidney" targets at depth in 34°C invivo pig thorax. CONCLUSION: A 915MHz antenna array can gently warm in vivo pig bladder without toxicity while a 1.375GHz radiometer with log spiral receive antenna detects ≥2°C rise in 30mL "urine" located 3-4cm deep in thorax, demonstrating more than sufficient sensitivity to detect Grade 4-5 reflux of warmed urine for non-invasive detection of VUR.

  10. Microwave radiometry for non-invasive detection of vesicoureteral reflux (VUR) following bladder warming

    NASA Astrophysics Data System (ADS)

    Stauffer, Paul R.; Maccarini, Paolo F.; Arunachalam, Kavitha; De Luca, Valeria; Salahi, Sara; Boico, Alina; Klemetsen, Oystein; Birkelund, Yngve; Jacobsen, Svein K.; Bardati, Fernando; Tognolotti, Piero; Snow, Brent

    2011-03-01

    Background: Vesicoureteral reflux (VUR) is a serious health problem leading to renal scarring in children. Current VUR detection involves traumatic x-ray imaging of kidneys following injection of contrast agent into bladder via invasive Foley catheter. We present an alternative non-invasive approach for detecting VUR by radiometric monitoring of kidney temperature while gently warming the bladder. Methods: We report the design and testing of: i) 915MHz square slot antenna array for heating bladder, ii) EMI-shielded log spiral microstrip receive antenna, iii) high-sensitivity 1.375GHz total power radiometer, iv) power modulation approach to increase urine temperature relative to overlying perfused tissues, and v) invivo porcine experiments characterizing bladder heating and radiometric temperature of aaline filled 30mL balloon "kidney" implanted 3-4cm deep in thorax and varied 2-6°C from core temperature. Results: SAR distributions are presented for two novel antennas designed to heat bladder and monitor deep kidney temperatures radiometrically. We demonstrate the ability to heat 180mL saline in in vivo porcine bladder to 40-44°C while maintaining overlying tissues <38°C using time-modulated square slot antennas coupled to the abdomen with room temperature water pad. Pathologic evaluations confirmed lack of acute thermal damage in pelvic tissues for up to three 20min bladder heat exposures. The radiometer clearly recorded 2-6°C changes of 30mL "kidney" targets at depth in 34°C invivo pig thorax. Conclusion: A 915MHz antenna array can gently warm in vivo pig bladder without toxicity while a 1.375GHz radiometer with log spiral receive antenna detects >=2°C rise in 30mL "urine" located 3-4cm deep in thorax, demonstrating more than sufficient sensitivity to detect Grade 4-5 reflux of warmed urine for non-invasive detection of VUR.

  11. Profilin 1 is a Potential Biomarker for Bladder Cancer Aggressiveness*

    PubMed Central

    Zoidakis, Jerome; Makridakis, Manousos; Zerefos, Panagiotis G.; Bitsika, Vasiliki; Esteban, Sergio; Frantzi, Maria; Stravodimos, Konstantinos; Anagnou, Nikolaos P.; Roubelakis, Maria G.; Sanchez-Carbayo, Marta; Vlahou, Antonia

    2012-01-01

    Of the most important clinical needs for bladder cancer (BC) management is the identification of biomarkers for disease aggressiveness. Urine is a “gold mine” for biomarker discovery, nevertheless, with multiple proteins being in low amounts, urine proteomics becomes challenging. In the present study we applied a fractionation strategy of urinary proteins based on the use of immobilized metal affinity chromatography for the discovery of biomarkers for aggressive BC. Urine samples from patients with non invasive (two pools) and invasive (two pools) BC were subjected to immobilized metal affinity chromatography fractionation and eluted proteins analyzed by 1D-SDS-PAGE, band excision and liquid chromatography tandem MS. Among the identified proteins, multiple corresponded to proteins with affinity for metals and/or reported to be phosphorylated and included proteins with demonstrated association with BC such as MMP9, fibrinogen forms, and clusterin. In agreement to the immobilized metal affinity chromatography results, aminopeptidase N, profilin 1, and myeloblastin were further found to be differentially expressed in urine from patients with invasive compared with non invasive BC and benign controls, by Western blot or Elisa analysis, nevertheless exhibiting high interindividual variability. By tissue microarray analysis, profilin 1 was found to have a marked decrease of expression in the epithelial cells of the invasive (T2+) versus high risk non invasive (T1G3) tumors with occasional expression in stroma; importantly, this pattern strongly correlated with poor prognosis and increased mortality. The functional relevance of profilin 1 was investigated in the T24 BC cells where blockage of the protein by the use of antibodies resulted in decreased cell motility with concomitant decrease in actin polymerization. Collectively, our study involves the application of a fractionation method of urinary proteins and as one main result of this analysis reveals the

  12. [Genetic and immunologic determinants of intravesical BCG therapy in non-muscle-invasive urothelial bladder cancer].

    PubMed

    Krajewski, Wojciech; Kołodziej, Anna; Dembowski, Janusz; Zdrojowy, Romuald

    2014-03-20

    Bladder cancer (BCA) is one of the most common cancers. In 2010 in Poland, 6296 people developed bladder cancer and 3110 people died of it. Immunotherapy with BCG (Bacillus Calmette-Guérin) is by far the most effective adjuvant therapy. Noninfiltrating muscle membrane changes, that is, stages Ta, Tis and T1 qualify for BCG immunotherapy. BCG immunotherapy comprises series of bladder instillations, containing attenuated strain of Mycobacterium bovis. The effectiveness of immunotherapy in non-invasive bladder cancer is 70% 5-year survival without recurrence of the tumor. The treatment leads to a reduction of the residual tumor mass, but also to the delay and/or prevention of relapse, disease progression and ultimately death. Cytokines, as key mediators of immune response, play an important role in the pathogenesis of bladder cancer, which occurrence is stimulated by the inflammatory process. BCG immunotherapy provokes an intensive immunological response by the increase of cytokine production. Genetic variants determine inter-individual differences in the incidence of this cancer, as well as the response to the therapy. This is evidenced by the presence of differences in genetic variants of cytokines correlated with the varied risk of bladder cancer incidence. It is believed that concentrations of particular cytokines in urine after installation of BCG may indicate response to the therapy. Increased levels of Th1 cytokines - IFN-γ, IL-2 and TNF-α are correlated with longer survival time without recurrence, whereas high levels of Th2 cytokines such as IL-10, predict unsuccessful BCG therapy.

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

    PubMed Central

    Gupta, Sunil; Gupta, Kavita; Ravi, R.; Mehta, Vinita; Banerjee, Samar; Joshi, Shashank; Saboo, Banshi

    2015-01-01

    Aim: To determine whether pioglitazone is associated with an increased risk of bladder cancer among Indian type 2 diabetic patients. Methods: A retrospective data analysis of 2222 type 2 diabetic patients was conducted. The study subjects were divided into two equal groups: 1111 pioglitazone users and 1111 pioglitazone non-users. The safety of pioglitazone therapy was analyzed in terms of occurrence of bladder and other types of cancers along with its efficacy in terms of glycemic control. Parameters for assessing safety were duration of disease, duration of usage and total dose of pioglitazone consumed across age groups, glycemic control, obesity and family history of any cancer. Bladder cancer prevalence was analyzed on the basis of urinary cytology, urine routine and microscopy, hematuria, urinary nuclear matrix protein 22 analysis and ultrasonography. Results: Of the 2222 cases analysed, there was no evidence of bladder cancer in any of the studied groups, (p=not significant) which was also evident among 1111 patients on Pioglitazone therapy with a cumulative dose consumption of 2737 mg to 1,31,400 mg. On subgroup analysis, there was no evidence of bladder cancer amongst patients with age >60 years, duration of diabetes > 10 years and uncontrolled diabetics (HbA1c >8%) with cumulative pioglitazone consumption of >28,000 mg. A significant number of patients achieved good glycemic control (HbA1c <7.5%) with pioglitazone therapy. Conclusion: Pioglitazone therapy was not associated with occurrence of bladder cancer among Indian type 2 diabetic patients and demonstrated good glycemic control. PMID:26425474

  14. Genetic variations in the transforming growth factor beta pathway as predictors of bladder cancer risk.

    PubMed

    Wei, Hua; Kamat, Ashish M; Aldousari, Saad; Ye, Yuanqing; Huang, Maosheng; Dinney, Colin P; Wu, Xifeng

    2012-01-01

    Bladder cancer is the fifth most common cancer in the United States, and identifying genetic markers that may predict susceptibility in high-risk population is always needed. The purpose of our study is to determine whether genetic variations in the transforming growth factor-beta (TGF-β) pathway are associated with bladder cancer risk. We identified 356 single-nucleotide polymorphisms (SNPs) in 37 key genes from this pathway and evaluated their association with cancer risk in 801 cases and 801 controls. Forty-one SNPs were significantly associated with cancer risk, and after adjusting for multiple comparisons, 9 remained significant (Q-value ≤0.1). Haplotype analysis further revealed three haplotypes within VEGFC and two haplotypes in EGFR were significantly associated with increased bladder cancer risk compared to the most common haplotype. Classification and regression tree analysis further revealed potential high-order gene-gene interactions, with VEGFC: rs3775194 being the initial split, which suggests that this variant is responsible for the most variation in risk. Individuals carrying the common genotype for VEGFC: rs3775194 and EGFR: rs7799627 and the variant genotype for VEGFR: rs4557213 had a 4.22-fold increase in risk, a much larger effect magnitude than that conferred by common genotype for VEGFR: rs4557213. Our study provides the first epidemiological evidence supporting a connection between TGF-β pathway variants and bladder cancer risk.

  15. The mechanism of action of BCG therapy for bladder cancer--a current perspective.

    PubMed

    Redelman-Sidi, Gil; Glickman, Michael S; Bochner, Bernard H

    2014-03-01

    Bacillus Calmette-Guérin (BCG) has been used to treat non-muscle-invasive bladder cancer for more than 30 years. It is one of the most successful biotherapies for cancer in use. Despite long clinical experience with BCG, the mechanism of its therapeutic effect is still under investigation. Available evidence suggests that urothelial cells (including bladder cancer cells themselves) and cells of the immune system both have crucial roles in the therapeutic antitumour effect of BCG. The possible involvement of bladder cancer cells includes attachment and internalization of BCG, secretion of cytokines and chemokines, and presentation of BCG and/or cancer cell antigens to cells of the immune system. Immune system cell subsets that have potential roles in BCG therapy include CD4(+) and CD8(+) lymphocytes, natural killer cells, granulocytes, macrophages, and dendritic cells. Bladder cancer cells are killed through direct cytotoxicity by these cells, by secretion of soluble factors such as TRAIL (tumour necrosis factor-related apoptosis-inducing ligand), and, to some degree, by the direct action of BCG. Several gaps still exist in our knowledge that should be addressed in future efforts to understand this biotherapy of cancer.

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

    PubMed Central

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

    2014-01-01

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

  17. Epidemiological case-control study on the etiology of bladder cancer in Turkey.

    PubMed

    Akdaş, A; Kirkali, Z; Bilir, N

    1990-01-01

    A case-control study of 194 patients with bladder cancer and the same number of age- and sex-matched hospital controls were interviewed to estimate the role of various factors on the etiology of bladder cancer in Turkey. There was a significant difference between the case and control groups on cigarette smoking (p less than 0.001), alcohol intake (p less than 0.001), Turkish coffee consumption (p = 0.01), and artificial sweeteners (p less than 0.05). The risks for alcohol and tobacco users increased in correlation with the duration of exposure. The risk of bladder cancer increased directly with the quantity and frequency of alcohol intake. Alcohol and coffee drinking was found to be a promoting factor when adjusted to smoking habits (p less than 0.05). No statistical comparisons could be made to clarify the risks attributed by occupation and place of residence due to small figures in each group. However, in farmers, there was a significant difference between the cases and controls on the use of artificial fertilizers and insecticides (p less than 0.01). People who were exposed to unspecified chemical substances were more prone to develop bladder cancer (p less than 0.001). We conclude that both personal habits and exogenous carcinogens play a role in the etiology of bladder tumors. PMID:2318234

  18. Nanoparticulation of BCG-CWS for application to bladder cancer therapy.

    PubMed

    Nakamura, Takashi; Fukiage, Masafumi; Higuchi, Megumi; Nakaya, Akihiro; Yano, Ikuya; Miyazaki, Jun; Nishiyama, Hiroyuki; Akaza, Hideyuki; Ito, Toshihiro; Hosokawa, Hiroyuki; Nakayama, Toshinori; Harashima, Hideyoshi

    2014-02-28

    The Mycobacterium bovis Bacille Calmette-Guerin cell wall skeleton (BCG-CWS) could be used to replace live BCG as a bladder cancer drug. However, because BCG-CWS is poorly soluble, has a strong-negative charge, very high molecular weight and heterogeneity in size of tens of μm, it cannot be used in such an application. We report herein on the development of a novel packaging method that permits BCG-CWS to be encapsulated into 166nm-sized lipid particles. The BCG-CWS encapsulated nano particle (CWS-NP) has a high uniformity and can be easily dispersed. Thus, it has the potential for use as a packaging method that would advance the scope of applications of BCG-CWS as a bladder cancer drug. In a functional evaluation, CWS-NP was efficiently taken up by mouse bladder tumor (MBT-2) cells in vitro and inhibited tumor growth in mice bearing MBT-2 tumors. Moreover, intravesically administered CWS-NP showed significant antitumor effects in a rat model with naturally developed bladder cancer. An enhancement in Th1 differentiation by CWS-NP was also confirmed in human T cells. In conclusion, CWS-NP represents a promising delivery system for BCG-CWS for clinical development as a potent bladder cancer drug.

  19. Risk of Alcohol Consumption in Bladder Cancer: Case-Control Study from a Nationwide Inpatient Database in Japan.

    PubMed

    Zaitsu, Masayoshi; Nakamura, Fumiaki; Toyokawa, Satoshi; Tonooka, Akiko; Takeuchi, Takumi; Homma, Yukio; Kobayashi, Yasuki

    2016-01-01

    Bladder cancer is common in Western countries, but not in Japan. Established risk factors are smoking and high-risk jobs such as printing and manufacturing. The risk of alcohol consumption in bladder cancer has been the recent focus; however, available literature on alcohol consumption and bladder cancer has been limited from Japanese population, thought to have a weak genetic tolerance to acetaldehyde. We aimed to determine whether alcohol consumption is an independent risk factor for bladder cancer among Japanese. The study was a matched case-control study from the nationwide Japanese clinical database administered by the Rosai Hospital group. We identified 739 cases of bladder cancer diagnosed between 2005 (when the database was established) and 2014 and 7,196 controls matched by sex, age, hospital, and admission period. We estimated the odds ratio of alcohol consumption for bladder cancer adjusted for the amount of smoking, high-risk occupations, and comorbidities (hypertension, hyperlipidemia, diabetes, hyperuricemia, and obesity) with conditional logistic regression. The risk of bladder cancer was significantly higher in ever drinkers than in never drinkers (odds ratio, 1.33; 95% confidence interval, 1.06 to 1.66). Furthermore, the risk threshold for alcohol consumption was more than 15 g of alcohol intake per day (one, 180-mL cup equivalent to 6 ounces of Japanese sake containing 23 grams of alcohol). Among Japanese, alcohol consumption may be an independent risk factor for bladder cancer, with a lower risk threshold. PMID:27098227

  20. Lower Urinary Tract Symptoms and Risk of Bladder Cancer in Men: Results from the Health Professionals Follow-Up Study

    PubMed Central

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

    2015-01-01

    Objectives To understand the association between Lower urinary tract symptoms (LUTS) and risk of bladder cancer in a large men's cohort. Methods Using data from the Health Professionals Follow-up Study, we examined risk of bladder cancer in relation to severity of LUTS among 30,183 men. During the follow-up period from 1996 until 2010, 476 newly diagnosed cases of bladder cancer occurred. Cox proportional hazards regression was used to adjust for potential confounders. Results Among men with severe LUTS, risk of bladder cancer was 64% higher (relative risk (RR): 1.64, 95% confidence interval (CI): 0.87, 3.08) compared with men who reported no LUTS. Subjects with both voiding and storage dysfunction had a significantly higher risk of bladder cancer (RR: 1.60, 95% confidence interval: 1.00, 2.56). Among individual urinary symptoms, urinary hesitancy was strongly associated with bladder cancer; those who experienced urinary hesitancy at least 50% of the time had more than twice the risk of bladder cancer (RR: 2.21, 95% CI: 1.29, 3.78). Conclusions Our findings suggest that LUTS, especially urinary hesitancy, are associated with the development of bladder cancer in men. PMID:25863833

  1. Biscoumarin derivatives: Synthesis, crystal structure, theoretical studies and induced apoptosis activity on bladder urothelial cancer cell

    NASA Astrophysics Data System (ADS)

    Xin, Jia-jia; Li, Jing; Zhang, Zi-dan; Hu, Xing-bin; Li, Ming-kai

    2015-03-01

    In this study, five new biscoumarin derivatives (1-5) were synthesized and compound 4 inhibited the proliferation of the bladder urothelial cells (J82 cell line) obviously after 48 h treatment at different concentration (1, 5 and 10 μmol/L), and J82 cells were predominantly induced to apoptotic cell death after compound 4 treatment. Morphologic changes of bladder urothelial cancer cells were also observed under transmission electron microscopy (TEM) after compound 4 treatment. In addition, compound 4 had much less toxicity to human umbilical vein endothelial cells. To explore the possible anti-cancer mechanism of compound 4, two classical intramolecular Osbnd H⋯O hydrogen bonds (HBs) in their structures and the corresponding HB energies were performed with the density functional theory (DFT) [B3LYP/6-31G∗] method. Anti-bladder cancer activity of compound 4 is possible due to the intramolecular weakest HB energies.

  2. Treatment options in non-muscle-invasive bladder cancer after BCG failure.

    PubMed

    Brooks, Nathan A; O'Donnell, Michael A

    2015-01-01

    Bladder cancer is the ninth-most prevalent cancer worldwide. Most patients with urothelial cell carcinoma of the bladder present with non-muscle-invasive disease and are treated with bacillus Calmette-Guérin (BCG) intravesical therapy. Many of these patients experience disease recurrence after BCG failure. Radical cystectomy is the recommended treatment for high-risk patients failing BCG. However, many patients are unfit for or unwilling to undergo this procedure. We searched the published literature on the treatment of non-muscle-invasive bladder cancer (NMIBC) after BCG failure. We review current evidence regarding intravesical therapy with gemcitabine, mitomycin combined with thermo-chemotherapy, docetaxel, nab-paclitaxel, photodynamic therapy (PDT), BCG with interferon (IFN), and combination sequentially administered chemotherapy.

  3. Case-control study of diesel exhaust exposure and bladder cancer

    SciTech Connect

    Wynder, E.L.; Dieck, G.S.; Hall, N.E.L.; Lahti, H.

    1985-08-01

    The relationship between bladder cancer and employment in occupations involving exposure to diesel exhaust was examined using data from a hospital-based case-control study of men aged 20 to 80 years in 18 hospitals in six US cities, from January 1981 to May 1983. In this analysis, 194 cases and 582 controls were compared according to occupation, smoking history, alcohol and coffee consumption, and various demographic variables. No difference was found in the proportion of bladder cancer cases employed in occupations with exposure to diesel exhaust compared to controls. This relationship did not change after taking smoking habits into account. Bladder cancer cases were significantly more likely to be current smokers of cigarettes than were controls.

  4. The Future of Intravesical Drug Delivery for Non-Muscle Invasive Bladder Cancer

    PubMed Central

    Douglass, Laura; Schoenberg, Mark

    2016-01-01

    Despite being the fifth most common cancer in the United States, minimal progress has been made in the treatment of bladder cancer in over a decade. Intravesical instillation of Bacillus Calmette-Guerin (BCG) for the treatment of non-muscle invasive bladder cancer (NMIBC) has been in use for over 30 years and remains the standard treatment in cases of intermediate and high risk disease. Despite the relative success of intravesical BCG, unmet needs in the treatment of NMIBC persist. These challenges include disease recurrence and progression even with treatment with BCG, as well as issues regarding its availability and patient tolerability. The inherent properties of the bladder pose the biggest obstacle to developing effective intravesical treatments for NMIBC. Current research is now focusing on methods to improve the delivery of intravesical therapies. The objective of this review is to discuss novel intravesical drug delivery systems and how they are addressing these challenges in the treatment of NMIBC. PMID:27500196

  5. Langerhans cell histiocytosis of the urinary bladder in a patient with bladder cancer previously treated with intravesical Bacillus Calmette-Guérin therapy.

    PubMed

    Numakura, Satoe; Morikawa, Teppei; Ushiku, Tetsuo; Toyoshima, Toyoaki; Fukayama, Masashi

    2014-02-01

    We report an extremely rare case of Langerhans cell histiocytosis (LCH) of the urinary bladder. A 68-year-old man presented with gross hematuria. Cystoscopy showed multiple papillary tumors in the urinary bladder, and transurethral resection was performed. Pathological diagnosis was high-grade papillary urothelial carcinoma with lamina propria invasion. The patient received six treatments with intravesical Bacillus Calmette-Guérin (BCG) therapy. Seven months after surgery, follow-up cystoscopy showed three elevated lesions in the urinary bladder, two of which were identified histologically as recurrent urothelial carcinoma. Microscopic examination of the lesion at the anterior wall revealed diffuse infiltration of medium to large histiocytoid cells in the lamina propria, many of which had distorted nuclei and nuclear grooves. Dense eosinophilic infiltration was also observed. Immunohistochemically, the histiocytoid cells were diffusely positive for S-100 and CD1a, but negative for cytokeratin AE1/AE3 and melanosome-associated antigen recognized by HMB-45. Based on the histological and immunohistochemical features, we diagnosed the lesion as LCH of the urinary bladder. There was no evidence of recurrence of either bladder cancer or LCH after an 18-month follow-up. To avoid misdiagnosis, urologists and pathologists should be aware that LCH may develop in the urinary bladder after intravesical BCG therapy for bladder cancer.

  6. Cancer detection by quantitative fluorescence image analysis.

    PubMed

    Parry, W L; Hemstreet, G P

    1988-02-01

    Quantitative fluorescence image analysis is a rapidly evolving biophysical cytochemical technology with the potential for multiple clinical and basic research applications. We report the application of this technique for bladder cancer detection and discuss its potential usefulness as an adjunct to methods used currently by urologists for the diagnosis and management of bladder cancer. Quantitative fluorescence image analysis is a cytological method that incorporates 2 diagnostic techniques, quantitation of nuclear deoxyribonucleic acid and morphometric analysis, in a single semiautomated system to facilitate the identification of rare events, that is individual cancer cells. When compared to routine cytopathology for detection of bladder cancer in symptomatic patients, quantitative fluorescence image analysis demonstrated greater sensitivity (76 versus 33 per cent) for the detection of low grade transitional cell carcinoma. The specificity of quantitative fluorescence image analysis in a small control group was 94 per cent and with the manual method for quantitation of absolute nuclear fluorescence intensity in the screening of high risk asymptomatic subjects the specificity was 96.7 per cent. The more familiar flow cytometry is another fluorescence technique for measurement of nuclear deoxyribonucleic acid. However, rather than identifying individual cancer cells, flow cytometry identifies cellular pattern distributions, that is the ratio of normal to abnormal cells. Numerous studies by others have shown that flow cytometry is a sensitive method to monitor patients with diagnosed urological disease. Based upon results in separate quantitative fluorescence image analysis and flow cytometry studies, it appears that these 2 fluorescence techniques may be complementary tools for urological screening, diagnosis and management, and that they also may be useful separately or in combination to elucidate the oncogenic process, determine the biological potential of tumors

  7. Zinc and copper levels in bladder cancer: a systematic review and meta-analysis.

    PubMed

    Mao, Song; Huang, Songming

    2013-06-01

    It is well documented that oxidative stress is involved in the pathogenesis of bladder cancer. Zinc (Zn) and copper (Cu) are important components of antioxidants. However, the association between Zn or Cu levels and bladder cancer remains elusive. The present study was designed to investigate the alteration of serum and urinary levels of Zn or Cu in bladder cancer patients compared with controls by performing a systematic review. We searched the PubMed, Embase, and Cochrane databases from January 1990 to March 2013 to identify studies that met our predefined criteria. Six studies were included. Bladder cancer patients demonstrated significantly lower levels of serum Zn (three studies, random effects standard mean deviation (SMD): -1.072, 95 % CI: -1.489 to -0.656, P <0.0001), markedly higher levels of serum Cu (three studies, random effects SMD: 1.069, 95 % CI: 0.302 to 1.836, P = 0.006) and urinary Zn (three studies, random effects SMD: 2.114, 95 % CI: 0.328 to 3.899, P = 0.02) compared with controls. No obvious difference was observed in urinary Cu levels between bladder cancer patients and controls (two studies, random effects SMD: 0.153, 95 % CI: -0.244 to 0.55, P = 0.449). No evidence of publication bias was observed. In conclusion, the disorder of Zn and Cu is closely associated with bladder cancer. Frequent monitoring and early intervention should be recommended.

  8. CYP2E1 and NQO1 genotypes and bladder cancer risk in a Lebanese population

    PubMed Central

    Basma, Hussein A; Kobeissi, Loulou H; Jabbour, Michel E; Moussa, Mohamad A; Dhaini, Hassan R

    2013-01-01

    Urinary bladder cancer incidence in Lebanon ranks among the highest in the world. Cytochrome P450 2E1 (CYP2E1), NAD(P)H quinone oxidoreductase1 (NQO1), and N-Acetyltransferase1 (NAT1), are drug-metabolizing enzymes (DMEs) involved in the metabolism of carcinogens, such as arylamines and heterocyclic amines, implicated in bladder cancer. The present study attempts to investigate the role of these DMEs genetic polymorphism in bladder cancer risk among Lebanese men. 54 cases and 106 controls were recruited from two hospitals in Beirut. An interview-based questionnaire was administered to assess suspected environmental and occupational risk factors. PCR-RFLP was performed on blood-based DNA samples to determine DMEs genotypes. Associations between bladder cancer and putative risk factors were measured using adjusted odds ratios (ORs) and their 95% confidence intervals (CIs). Results showed CYP2E1 c1/c1, NAT1*14A, and smoking, to be risk factors for bladder cancer. No significant differences in frequency distribution of the NQO1 genotypes were found in cases versus controls. The odds of carrying the CYP2E1 c1/c1 genotype were 4 times higher in cases compared to controls (OR=3.97, 95% CI: 0.48-32.7). The odds of carrying at least one NAT1*14A allele were 14 times higher in cases versus controls (OR=14.4, 95% CI: 1.016-204.9). Our study suggests CYP2E1 c1/c1, NAT1*14A, and smoking, as potential risk factors for bladder cancer in Lebanese. Further studies with larger samples must be conducted to confirm these findings. PMID:24319536

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

    PubMed

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

    2014-01-01

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

  10. Metformin and gefitinib cooperate to inhibit bladder cancer growth via both AMPK and EGFR pathways joining at Akt and Erk

    PubMed Central

    Peng, Mei; Huang, Yanjun; Tao, Ting; Peng, Cai-Yun; Su, Qiongli; Xu, Wanjun; Darko, Kwame Oteng; Tao, Xiaojun; Yang, Xiaoping

    2016-01-01

    EGFR is a potential therapeutic target for treating bladder cancer, but has not been approved for clinical use yet. Metformin is a widely used antidiabetic drug and has demonstrated interesting anticancer effects on various cancer models, alone or in combination with chemotherapeutic drugs. The efficacy of gefitinib, a well-known EGFR tyrosine kinase inhibitor, combined with metformin was assessed on bladder cancer and underlying mechanisms were explored. This drug combination induced a strong anti-proliferative and anti-colony forming effect and apoptosis in bladder cancer