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Sample records for bladder cancer development

  1. Bladder Cancer Advocacy Network

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2016-01-01

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

  3. What Is Bladder Cancer?

    Science.gov (United States)

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

  4. Treatment Option Overview (Bladder Cancer)

    Science.gov (United States)

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

  5. Scoring system development for prediction of extravesical bladder cancer

    Directory of Open Access Journals (Sweden)

    Prelević Rade

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Othman Fethi

    2011-03-01

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

  8. Bladder Cancer Risk Prediction Models

    Science.gov (United States)

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

  9. Neoadjuvant paradigm for accelerated drug development: an ideal model in bladder cancer.

    Science.gov (United States)

    Chism, David D; Woods, Michael E; Milowsky, Matthew I

    2013-01-01

    Neoadjuvant cisplatin-based combination chemotherapy for muscle-invasive bladder cancer (MIBC) has been shown to confer a survival advantage in two randomized clinical trials and a meta-analysis. Despite level 1 evidence supporting its benefit, utilization remains dismal with nearly one-half of patients ineligible for cisplatin-based therapy because of renal dysfunction, impaired performance status, and/or coexisting medical problems. This situation highlights the need for the development of novel therapies for the management of MIBC, a disease with a lethal phenotype. The neoadjuvant paradigm in bladder cancer offers many advantages for accelerated drug development. First, there is a greater likelihood of successful therapy at an earlier disease state that may be characterized by less genomic instability compared with the metastatic setting, with an early readout of activity with results determined in months rather than years. Second, pre- and post-treatment tumor tissue collection in patients with MIBC is performed as the standard of care without the need for research-directed biopsies, allowing for the ability to perform important correlative studies and to monitor tumor response to therapy in "real time." Third, pathological complete response (pT0) predicts for improved outcome in patients with MIBC. Fourth, there is a strong biological rationale with rapidly accumulating evidence for actionable targets in bladder cancer. This review focuses on the neoadjuvant paradigm for accelerated drug development using bladder cancer as the ideal model.

  10. [Occupational hazards and bladder cancer].

    Science.gov (United States)

    Nizamova, R S

    1991-01-01

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

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

    DEFF Research Database (Denmark)

    Zieger, Karsten; Marcussen, Niels; Borre, Michael

    2009-01-01

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

  12. Developments in diagnosis and prognosis of superficial bladder cancer

    NARCIS (Netherlands)

    Moonen, P.M.J.

    2007-01-01

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

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

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    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.

  14. Genetics Home Reference: bladder cancer

    Science.gov (United States)

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

  15. Innovation in Bladder Cancer Immunotherapy.

    Science.gov (United States)

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

    2016-10-01

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

  16. Molecular Diagnosis in Bladder Cancer

    NARCIS (Netherlands)

    T.C.M. Zuiverloon (Tahlita)

    2013-01-01

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

  17. Metabolic phenotype of bladder cancer.

    Science.gov (United States)

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

    2016-04-01

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

  18. Neoadjuvant therapy in muscle-invasive bladder cancer: a model for rational accelerated drug development.

    Science.gov (United States)

    Balar, Arjun V; Milowsky, Matthew I

    2015-05-01

    Since the advent of cisplatin-based combination therapy in the management of muscle-invasive and advanced bladder cancer, there has been little progress in improving outcomes for patients. Novel therapies beyond cytotoxic chemotherapy are needed. The neoadjuvant paradigm lends to acquiring ample pretreatment and posttreatment tumor tissue as a standard of care, which enables comprehensive biomarker analyses to better understand mechanisms of both response and resistance, which will aid drug development. This article discusses the evolution of neoadjuvant therapy as standard treatment and the role it may serve toward the development of novel therapies.

  19. Chemoprevention of bladder cancer.

    Science.gov (United States)

    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

  20. Emerging Immunotargets in Bladder Cancer.

    Science.gov (United States)

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

    2016-01-01

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

  1. Drugs Approved for Bladder Cancer

    Science.gov (United States)

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

  2. Spectroscopic Imaging of Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-01-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2012-06-01

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

  5. MOLECULAR PROGNOSTIC MARKERS OF URINE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    V. N. Pavlov

    2012-01-01

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

  6. Progress in Personalizing Chemotherapy for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    James S. Chang

    2012-01-01

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

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

    Science.gov (United States)

    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.

  8. Photodynamic management of bladder cancer

    Science.gov (United States)

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

    2009-06-01

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

  9. Role of Rip2 in development of tumor-infiltrating MDSCs and bladder cancer metastasis.

    Directory of Open Access Journals (Sweden)

    Hanwei Zhang

    Full Text Available Tumor invasion and metastases represent a complex series of molecular events that portends a poor prognosis. The contribution of inflammatory pathways mediating this process is not well understood. Nod-like receptors (NLRs of innate immunity function as intracellular sensors of pathogen motifs and danger molecules. We propose a role of NLRs in tumor surveillance and in programming tumor-infiltrating lymphocytes (TILs. In this study, we examined the downstream serine/threonine and tyrosine kinase Rip2 in a murine model of bladder cancer. In Rip2-deficient C57Bl6 mice, larger orthotopic MB49 tumors developed with more numerous and higher incidence of metastases compared to wild-type controls. As such, increased tumor infiltration of CD11b+ Gr1hi myeloid-derived suppressor cells (MDSCs with concomitant decrease in T cells and NK cells were observed in Rip2-deficient tumor bearing animals using orthotopic and subcutaneous tumor models. Rip2-deficient tumors showed enhanced epithelial-to-mesenchymal transition, with elevated expression of zeb1, zeb2, twist, and snail in the tumor microenvironment. We found that the absence of Rip2 plays an intrinsic role in fostering the development of granulocytic MDSCs by an autocrine and paracrine effect of granulocytic colony stimulating factor (G-CSF expression. Our findings suggest that NLR pathways may be a novel modality to program TILs and influence tumor metastases.

  10. Pathology of bilharzial bladder cancer.

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    Godwin, J T; Hanash, K

    1984-01-01

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

  11. Surveillance of bladder cancer

    NARCIS (Netherlands)

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

    2009-01-01

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

  12. Bladder cancer: molecular determinants of personalized therapy.

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Smith, Sean G; Zaharoff, David A

    2016-01-01

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

  14. The Danish Bladder Cancer Database

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  15. URINARY BLADDER CANCER WITH FOCUS ON OCCUPATIONAL DYE WORKERS

    Directory of Open Access Journals (Sweden)

    K.Revathi

    2015-11-01

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

  16. DEVELOPMENT OF THE NOMOGRAM THAT PREDICTS PATHOLOGICAL LYMPH NODE INVOLVEMENT IN BLADDER CANCER PATIENTS BASED ON CLINICAL VARIABLES

    Directory of Open Access Journals (Sweden)

    L. V. Mirylenko

    2012-01-01

    Full Text Available Objective: to develop nomogram based on clinical variables, that predicts pathological lymph node involvement (рN+ in bladder cancer patients.Material and methods: We used data of 511 patients with bladder cancer, that have undergone radical cystectomy between 1999 and 2008 at N.N. Alexandrov National Cancer Centre. Mono- and multivariate logistic regression analyses were used for pN+ prediction on preoperative data. Coefficients from logistic regression equation were used to construct the nomogram. Nomogram accuracy was evaluated with concordance index and construction of the calibration plot. Internal validation by bootstrap method with 200 variants of dataset was performed.Results: We developed nomogram, that includes: clinical stage сТ, tumor grade, tumor macroscopic appearance, and creatinine level. Bootstrap-corrected prognostic accuracy of nomogram was 71,6%, that was 9,4% better than clinical stage accuracy.Conclusion: utilization of developed nomogram can significantly improve pathologic tumor stage prediction accuracy that may be used to select patients for neoadjuvant chemotherapy.

  17. DEVELOPMENT OF THE NOMOGRAM THAT PREDICTS PATHOLOGICAL LYMPH NODE INVOLVEMENT IN BLADDER CANCER PATIENTS BASED ON CLINICAL VARIABLES

    Directory of Open Access Journals (Sweden)

    L. V. Mirylenko

    2014-07-01

    Full Text Available Objective: to develop nomogram based on clinical variables, that predicts pathological lymph node involvement (рN+ in bladder cancer patients.Material and methods: We used data of 511 patients with bladder cancer, that have undergone radical cystectomy between 1999 and 2008 at N.N. Alexandrov National Cancer Centre. Mono- and multivariate logistic regression analyses were used for pN+ prediction on preoperative data. Coefficients from logistic regression equation were used to construct the nomogram. Nomogram accuracy was evaluated with concordance index and construction of the calibration plot. Internal validation by bootstrap method with 200 variants of dataset was performed.Results: We developed nomogram, that includes: clinical stage сТ, tumor grade, tumor macroscopic appearance, and creatinine level. Bootstrap-corrected prognostic accuracy of nomogram was 71,6%, that was 9,4% better than clinical stage accuracy.Conclusion: utilization of developed nomogram can significantly improve pathologic tumor stage prediction accuracy that may be used to select patients for neoadjuvant chemotherapy.

  18. Stages of Bladder Cancer

    Science.gov (United States)

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

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

    Directory of Open Access Journals (Sweden)

    Cheung Grace

    2013-01-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  2. Clinical states model for biomarkers in bladder cancer.

    Science.gov (United States)

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

    2009-09-01

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

  3. Neoadjuvant chemotherapy for invasive bladder cancer.

    Science.gov (United States)

    Sonpavde, Guru; Sternberg, Cora N

    2012-04-01

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

  4. Bladder cancer; Cancer de la Vessie

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-07-01

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

  5. Urinary Bladder Cancer in Yemen

    Science.gov (United States)

    Al-Samawi, Abdullah Saleh; Aulaqi, Saleh Mansoor

    2013-01-01

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

  6. Urinary Bladder Cancer in Yemen

    Directory of Open Access Journals (Sweden)

    Abdullah Saleh Al-Samawi

    2013-09-01

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

  7. Genetic variant as a marker for bladder cancer therapy

    Science.gov (United States)

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

  8. Mutational Context and Diverse Clonal Development in Early and Late Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Iver Nordentoft

    2014-06-01

    Full Text Available Bladder cancer (or urothelial cell carcinoma [UCC] is characterized by field disease (malignant alterations in surrounding mucosa and frequent recurrences. Whole-genome, exome, and transcriptome sequencing of 38 tumors, including four metachronous tumor pairs and 20 superficial tumors, identified an APOBEC mutational signature in one-third. This was biased toward the sense strand, correlated with mean expression level, and clustered near breakpoints. A > G mutations were up to eight times more frequent on the sense strand (p < 0.002 in [ACG]AT contexts. The patient-specific APOBEC signature was negatively correlated to repair-gene expression and was not related to clinicopathological parameters. Mutations in gene families and single genes were related to tumor stage, and expression of chromatin modifiers correlated with survival. Evolutionary and subclonal analyses of early/late tumor pairs showed a unitary origin, and discrete tumor clones contained mutated cancer genes. The ancestral clones contained Pik3ca/Kdm6a mutations and may reflect the field-disease mutations shared among later tumors.

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

    Science.gov (United States)

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

    2009-09-15

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

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

    Directory of Open Access Journals (Sweden)

    Sylvain Chawki

    2014-11-01

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

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

    Science.gov (United States)

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

    2016-04-27

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

  12. NOTCH pathway inactivation promotes bladder cancer progression.

    Science.gov (United States)

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

    2015-02-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

  14. Novel non invasive diagnostic strategies in bladder cancer.

    Science.gov (United States)

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

    2016-01-01

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

  15. Tetrachloroethylene exposure and bladder cancer risk

    DEFF Research Database (Denmark)

    Vlaanderen, Jelle; Straif, Kurt; Ruder, Avima

    2014-01-01

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

  16. Current therapeutic strategies for invasive and metastatic bladder cancer

    Directory of Open Access Journals (Sweden)

    Vishnu P

    2011-07-01

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

  17. Lymphatic vessel density and function in experimental bladder cancer

    Directory of Open Access Journals (Sweden)

    Maier Julie

    2007-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Douglas G Ward

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  20. Development of new inhibitors for N-acylethanolamine-hydrolyzing acid amidase as promising tool against bladder cancer.

    Science.gov (United States)

    Vago, Riccardo; Bettiga, Arianna; Salonia, Andrea; Ciuffreda, Pierangela; Ottria, Roberta

    2017-02-01

    The endocannabinoid system is a signaling system involved in a wide range of biological effects. Literature strongly suggests the endocannabinoid system role in the pathogenesis of cancer and that its pharmacological activation produces therapeutic benefits. Last research promotes the endocannabinoid system modulation by inhibition of endocannabinoids hydrolytic enzymes instead of direct activation of endocannabinoid receptors to avoid detrimental effects on cognition and motor control. Here we report the identification of N-acylethanolamine-hydrolyzing acid amidase (NAAA) inhibitors able to reduce cell proliferation and migration and cause cell death on different bladder cancer cell lines. These molecules were designed, synthesized and characterized and active compounds were selected by a fluorescence high-throughput screening method set-up on human recombinant NAAA that also allows to characterize the mechanism of inhibition. Together our results suggest an important role for NAAA in cell migration and in inducing tumor cell death promoting this enzyme as pharmacological target against bladder cancer.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Tomokazu Ohishi

    2015-12-01

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

  3. Expression and Significance of Oct4 in Bladder Cancer

    Institute of Scientific and Technical Information of China (English)

    XU Kai; ZHU Zhaohui; ZENG Fuqing; DONG Jihua

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Letašiová Silvia

    2012-06-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Ishizu, Sumiko; Hashida, Chise

    2007-01-01

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

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

    Science.gov (United States)

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

    1995-03-01

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

  8. Optimizing systemic therapy for bladder cancer.

    Science.gov (United States)

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

    2013-07-01

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

  9. Hemipelvic irradiation for superficial bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-02-01

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

  10. Paraneoplastic retinopathy associated with occult bladder cancer

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  13. Radical radiotherapy for urinary bladder cancer

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  14. Impact of proteomics on bladder cancer research

    DEFF Research Database (Denmark)

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

    2004-01-01

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

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

    Science.gov (United States)

    Chiu, Melody; McBeth, Lucien; Sindhwani, Puneet

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Gulay Ceylan

    2016-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Xu Li-Hua

    2009-02-01

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

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

    OpenAIRE

    Rathore, Kusum; Cekanova, Maria

    2014-01-01

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

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

    OpenAIRE

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

    2016-01-01

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

  20. Automatic staging of bladder cancer on CT urography

    Science.gov (United States)

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

    2016-03-01

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

  1. Microsatellite instability in bladder cancer

    DEFF Research Database (Denmark)

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

    1993-01-01

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

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

    Directory of Open Access Journals (Sweden)

    2015-01-01

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

  3. PHOTODYNAMIC DIAGNOSIS AND FLUORESCENCE SPECTROSCOPY IN SUPERFICIAL BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    I. G. Rusakov

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sarah R. Ambrose

    2015-09-01

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

  5. BCG and the treatment of superficial bladder cancer.

    Science.gov (United States)

    Moss, J T; Kadmon, D

    1991-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Dong-Suk Kim

    2002-02-01

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

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

    OpenAIRE

    2002-01-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

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

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  10. Preoperative irradiation and cystectomy for bladder cancer.

    Science.gov (United States)

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

    1982-03-01

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

  11. General Information about Bladder Cancer

    Science.gov (United States)

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

  12. Dogs Sniff out Bladder Cancer

    Institute of Scientific and Technical Information of China (English)

    Helen Pearson; 秦阳阳

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Thomas Reinert

    2012-01-01

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

  14. Oncolytic Viruses in the Treatment of Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Kyle G. Potts

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

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

    Science.gov (United States)

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

    2015-02-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  19. IMMUNOHISTOCHEMICAL ANALYSIS OF UROTHELIAL BLADDER CANCERS

    Directory of Open Access Journals (Sweden)

    Katarina Bevizova

    2013-01-01

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

  20. Bladder Cancer Immunotherapy: BCG and Beyond

    Directory of Open Access Journals (Sweden)

    Eric J. Askeland

    2012-01-01

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

  1. Bladder Cancer Immunotherapy: BCG and Beyond.

    Science.gov (United States)

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

    2012-01-01

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

  2. Occupational exposure to solvents and bladder cancer

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  3. Antibody conjugate radioimmunotherapy of superficial bladder cancer

    Directory of Open Access Journals (Sweden)

    Alan Perkins

    2002-09-01

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

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

    Science.gov (United States)

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

    2011-12-01

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

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

    Science.gov (United States)

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

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

  6. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2006-02-01

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

  8. Reduced LAK cytotoxicity of peripheral blood mononuclear cells in patients with bladder cancer

    DEFF Research Database (Denmark)

    Hermann, G G; Petersen, K R; Steven, K

    1990-01-01

    The cytotoxicity of unstimulated peripheral blood mononuclear cells (US-PBMC), phytohemagglutinin (PHA)-stimulated PBMC (PS-PBMC) and interleukin-2 (IL-2)-activated PBMC (LAK cells) was assessed in patients with noninvasive and invasive transitional-cell bladder cancer and compared with those...... determined in healthy controls. The differences in the cytotoxicities were correlated with specific changes in the subsets of peripheral blood mononuclear cells (PBMC). PBMC from 37 patients and 13 healthy controls were tested against the bladder cancer cell line T24 in 51Cr-release assays. The PBMC subsets...... that the reduced ability of bladder cancer patient PBMC to develop LAK-cell cytotoxicity is a result of a low incidence of CD56+ and CD57+ cells in the blood. These findings indicate that IL-2 therapy alone might not be a sufficient therapy of bladder cancer patients....

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

    Science.gov (United States)

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

    2011-03-07

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

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

    Directory of Open Access Journals (Sweden)

    Shengjie Guo

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

  11. 18F-FDG PET/CT in Bladder Cancer.

    Science.gov (United States)

    Tagliabue, Luca; Russo, Giovanna; Lucignani, Giovanni

    2016-12-01

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

  12. Vinflunine in the treatment of bladder cancer

    Directory of Open Access Journals (Sweden)

    Mark Bachner

    2008-11-01

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

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

    Science.gov (United States)

    Chang, S C; Bown, S G

    1997-11-01

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

  14. A murine model for bladder cancer.

    Science.gov (United States)

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

    1984-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Tinawi-Aljundi R

    2015-04-01

    Full Text Available Rima Tinawi-Aljundi,1 Lauren King,2 Shannon T Knuth,2 Michael Gildea,2 Carrie Ng,2 Josh Kahl,2 Jacqueline Dion,2 Chris Young,2 Edward W Schervish,1 J Rene Frontera,1 Jason Hafron,1 Kenneth M Kernen,1 Robert Di Loreto,1 Joan Aurich-Costa21Michigan Institute of Urology, St Claire Shores, MI, USA; 2Cellay, Inc., Cambridge, MA, USA Background: Previously, we had developed and manufactured an oligonucleotide fluorescence in situ hybridization (OligoFISH probe panel based on the most clinically sensitive chromosomes found in a reference set of bladder carcinoma cases. The panel was clinically validated for use as a diagnostic and monitoring assay for bladder cancer, reaching 100% correlation with the results of the UroVysion test. After 1 year of using this probe panel, we present here the comparison of cytology, cystoscopy, and pathology findings to the OligoFISH probe panel results to calculate its clinical performance. Materials and methods: In order to calculate clinical performance, we compared the OligoFISH results to the cytology and cystoscopy/pathology findings for 147 initial diagnoses and 399 recurrence monitorings. Finally, we compared clinical performance to published values for the UroVysion test, including both low- and high-grade tumors. Results: Chromosomes 3, 6, 7, and 20 were highly involved in bladder carcinoma aneuploidy. At the initial diagnosis, we obtained 90.5% (95% confidence interval [CI]: 84.5%–94.7% accuracy, 96.8% sensitivity (95% CI: 91.0%–99.3%, 79.2% specificity (95% CI: 65.9%–87.8%, 89.2% positive predictive value (PPV; 95% CI: 81.5%–94.5%, and 93.3% negative predictive value (NPV; 95% CI: 81.7%–97.3%. When monitoring for recurrence, we obtained 85.2% accuracy (95% CI: 81.3%–88.5%, 82.0% sensitivity (95% CI: 76.0%–87.1%, 88.4% specificity (95% CI: 83.2%–92.5%, 87.7% PPV (95% CI: 82.1%–92.0%, and 83.0% NPV (95% CI: 77.3%–87.8%. When looking at low- and high-grade tumors, the test showed 100

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

    Science.gov (United States)

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

    2015-05-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2011-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Jin X

    2016-09-01

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

  20. What Are the Risk Factors for Bladder Cancer?

    Science.gov (United States)

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

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

    OpenAIRE

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

    1998-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

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

  3. Management of the urethra in urothelial bladder cancer

    OpenAIRE

    Kanaroglou, Androniki; Shayegan, Bobby

    2009-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-02-01

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

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

    Science.gov (United States)

    Netto, George J

    2013-11-01

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

  6. Combined intraarterial cisplatin infusion and radiation therapy for invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mizoguchi, Hiroaki; Nomura, Yoshio; Terada, Katsuhiko; Nakagawa, Masayuki; Ogata, Jiro [Oita Medical Univ., Hasama (Japan)

    1995-03-01

    Twenty-three patients with invasive bladder cancer (T2 in 17, T3 in 6) were treated initially with combined intraarterial cisplatin infusion and radiation therapy. Cisplatin (50 mg) was infused into the internal iliac artery through a subcutaneous reservoir twice a week over three weeks while concurrent radiation therapy with 30 Gy, delivered in 15 fractions, was given. In 23 patients, 6 received additional cisplatin infusion and the other 17 had transurethral resection of bladder tumor (TURBT). Two of the patients undergoing total cystectomy exhibited a complete response (CR). Thus overall response rate was 87% (CR in 13 and partial response in 7). CR was achieved in 53% for T2 patients and 67% for T3 patients. CR was slightly higher in patients with non-papillary cancer than those with papillary one. Toxic reaction included a decrease in bladder capacity in 2 patients and severe diarrhea due to methicillin-resistant Staphylococcus aureus colitis in one. The other toxicities, including nausea, vomiting, neurotoxicity and myelosuppression, were tolerable. All except for one are alive. Seven patients had a local recurrence of bladder cancer. One patient developed invasive bladder cancer reaching the prostatic urethra. One other patient had recurrence at the same site as the previous tumor. Five others had superficial bladder cancer and were managed by TURBT. Bladder function was preserved in 65% at a mean follow-up of 29 months. In conclusion, the combined intraarterial cisplatin infusion and radiation therapy is useful for the initial treatment of invasive bladder cancer. (N.K.).

  7. Summary of the 6th Annual Bladder Cancer Think Tank: new directions in urologic research.

    Science.gov (United States)

    Svatek, Robert S; Rosenberg, Jonathan E; Galsky, Matthew D; Lee, Cheryl T; Latini, David M; Bochner, Bernard H; Weizer, Alon Z; Apolo, Andrea B; Sridhar, Srikala S; Kamat, Ashish M; Hansel, Donna; Flaig, Thomas W; Smith, Norm D; Lotan, Yair

    2013-10-01

    The 6th Annual Bladder Cancer Think Tank brought together a multidisciplinary group of clinicians, researchers, and representatives from the National Cancer Institute and Industry in an effort to advance bladder cancer research efforts. This year's meeting comprised panel discussions and research involving 5 separate working groups, including the Survivorship, Clinical Trials, Standardization of Care, Data Mining, and Translational Science working groups. In this manuscript, the accomplishments and objectives of the working groups are summarized. Notable efforts include: (1) the development of a survivorship care plan for early and late-stage bladder cancer; (2) the development of consensus criteria for eligibility and endpoints for bladder cancer clinical trials; (3) an improved understanding of current practice patterns regarding the use of perioperative chemotherapy in an effort to standardize care; (4) creation of a comprehensive handbook to assist researchers with developing bladder cancer databases; and (5) identification of response to therapy of high-grade non muscle invasive disease through a collaborative exchange of expertise and resources.

  8. Focal S100A4 protein expression is an independent predictor of development of metastatic disease in cystectomized bladder cancer patients

    DEFF Research Database (Denmark)

    Agerbæk, Mads; Alsner, Jan; Marcussen, Niels

    2006-01-01

    , compared with the pattern of relapses over a 10+ yr follow-up period. RESULTS: Focal S100A4 protein expression emerged as the only significant independent predictor of distant metastatic relapse and distant metastasis-free survival in multivariate analysis. CONCLUSION: There is a potential role......OBJECTIVE: The prognosis of patients with apparently localized, operable, muscle-invasive bladder cancer depends to a large extent on the presence or absence of subclinical, microscopic distant metastases at the time of surgery. Expression of the S100A4 protein has been shown to correlate...... with the risk of metastasis in both animal tumour-model systems and clinical investigations in other tumour types. The purpose of the present study was to investigate the prognostic potential of S100A4 protein expression for predicting distant metastatic relapse in muscle-invasive bladder cancer. METHODS: We...

  9. Quantitative assessment of the relationship between RASSF1A gene promoter methylation and bladder cancer (PRISMA)

    Science.gov (United States)

    Zhan, Leyun; Zhang, Bingyi; Tan, Yaojun; Yang, Chengliang; Huang, Chenhong; Wu, Qiongya; Zhang, Yulin; Chen, Xiaobo; Zhou, Mi; Shu, Aihua

    2017-01-01

    Abstract Background: Methylation of the Ras-association domain family 1 isoform A (RASSF1A) gene promoter region is thought to participate in the initiation and development of many different cancers. However, in bladder cancer the role of RASSF1A methylation was unclear. To evaluate the relationship between RASSF1A methylation and bladder cancer, a quantitative assessment of an independent meta-analysis was performed. In addition, a DNA methylation microarray database from the cancer genome atlas (TCGA) project was used to validate the results of the meta-analysis. Methods: We searched published articles from computerized databases, and DNA methylation data were extracted from TCGA project. All data were analyzed by R software. Results: The results of the meta-analysis indicated that the frequency of RASSF1A gene methylation in bladder cancer patients is significantly higher than in healthy controls. The hazard ratio (HR) was 2.24 (95% CI = [1.45; 3.48], P = 0.0003) for overall survival (OS), and the RASSF1A gene promoter methylation status was strongly associated with the TNM stage and differentiation grade of the tumor. The similar results were also found by the data from TCGA project. Conclusion: There was a significant relationship between the methylation of the RASSF1A gene promoter and bladder cancer. Therefore, RASSF1A gene promoter methylation will be a potential biomarker for the clinical diagnosis of bladder cancer. PMID:28207521

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

    Science.gov (United States)

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

    2010-01-01

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

  11. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

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

    2006-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  13. Novel Gelatin-Adriamycin Sustained Drug Release System for Intravesical Therapy of Bladder Cancer

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To reduce recurrence in the patients with bladder cancer after tumor removal through open surgery or transurethral resection, a form of gelatin-adriamycin sustained drug release system was developed and its release kinetics both in vitro and in vivo, its efficacy in inhibiting BIU-87 bladder tumor cell growth in vitro and its safety in vivo were studied. The results showed that this system controlled adriamycin release over a period of 21 days in vitro and significantly inhibited BIU-87 cell growth. When this system was injected into rabbit bladder, it sustained adriamycin release for 12 days and the released drug could diffuse 1 cm around the injection point. No major complications were observed except minor acute nonspecific cystitis that could be tolerated well by the animals. This study suggests the possibility of applying this system locally in treating bladder cancer.

  14. Levels of certain tumor markers as differential factors between bilharzial and non-biharzial bladder cancer among Egyptian patients

    Directory of Open Access Journals (Sweden)

    Mohamed Azza M

    2011-04-01

    Full Text Available Abstract Background/Objective Bladder cancer is the commonest type of malignant tumors as a result of schistosomaisis which is a major healthy problem in many subtropical developing countries. The aim of this study is to comparatively elucidate the underlying biochemical tumor markers in schistosomal bladder cancer versus non-schistosomal bladder cancer when compared to normal healthy ones. Methods This work was performed on tissue specimens from total 25 patients and serum samples from total 30 patients versus ten healthy individuals served as control. The investigated parameters in serum are: xanthine oxidase (XO, fructosamine, lactate dehydrogense (LDH, aspartate aminotransferase (AST, alanine aminotransferase (ALT, total proteins, essential and non- essential amino acids profile, hydroxyproline, total immunoglobulin E (IgE and tumor necrosis factor alpha (TNF-α. In addition, the current investigation also extended to study some markers in tumor bladder tissues including, pyruvate kinase enzyme (PK, lactate dehydrogenase (LDH, aspartate aminotransferase (AST and alanine aminotransferase (ALT. Results Results showed that biharzial bladder cancer patients recored more significant elevation in serum XO, fructosamine, LDH, AST, ALT, hydroxyproline, IgE and TNF-α than in bladder cancer patients when compared to control ones. While, in tissues there were significant increase in PK, LDH, AST & ALT activities of schistosomal bladder cancer than in bladder cancer as compared to control healthy patients. Conclusions It could be concluded that, bilharzial and non-bilharzial bladder cancer showed distinct biochemical profile of tumor development and progression which can be taken into consideration in diagnosis of bladder cancer.

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

    OpenAIRE

    Liang, Enli

    2016-01-01

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

  16. Characterization of different carbon nanotubes for the development of a mucoadhesive drug delivery system for intravesical treatment of bladder cancer.

    Science.gov (United States)

    Rieger, Christiane; Kunhardt, David; Kaufmann, Anika; Schendel, Darja; Huebner, Doreen; Erdmann, Kati; Propping, Stefan; Wirth, Manfred P; Schwenzer, Bernd; Fuessel, Susanne; Hampel, Silke

    2015-02-20

    In order to increase the effectiveness of therapeutics for bladder carcinoma (BCa) treatment, alternative strategies for intravesical applications are needed. The use of carbon nanotubes (CNTs) as basis for a multifunctional drug transporter is a promising possibility to combine traditional chemotherapeutics with innovative therapeutic agents such as antisense oligodeoxynucleotides or small interfering RNA. In the current study four CNT types varying in length and diameter (CNT-1, CNT-2, CNT-3, CNT-4) were synthesized and then characterized with different spectroscopic techniques. Compared to the pristine CNT-1 and CNT-3, the shortened CNT-2 and CNT-4 exhibited more defects and lower aspect ratios. To analyze their mucoadhesive properties, CNTs were exposed to mouse bladders ex vivo by using Franz diffusion cells. All four tested CNT types were able to adhere to the urothelium with a mean covering area of 5-10%. In vitro studies on UM-UC-3 and EJ28 BCa cells were conducted to evaluate the toxic potential of these CNTs. Viability and cytotoxicity assays revealed that the shortened CNT-2 and CNT-4 induced stronger inhibitory effects on BCa cells than CNT-1 and CNT-3. In conclusion, CNT-1 and CNT-3 showed the most promising properties for further optimization of a multifunctional drug transporter.

  17. HPLC assisted Raman spectroscopic studies on bladder cancer

    Science.gov (United States)

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

    2015-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Ahmad Keshtkar

    2012-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Ning [Faculty of Health Science, Suzuka University of Medical Science, Suzuka, Mie (Japan); Thanan, Raynoo [Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie (Japan); Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie (Japan); Kobayashi, Hatasu [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie (Japan); Hammam, Olfat; Wishahi, Mohamed; Leithy, Tarek El [Departments of Pathology and Urology, Theodor Bilharz Research Institute, Giza (Egypt); Hiraku, Yusuke [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie (Japan); Amro, EL-Karef [Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Mie (Japan); Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura (Egypt); Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie (Japan); Ohnishi, Shiho [Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie (Japan); Murata, Mariko [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie (Japan); Kawanishi, Shosuke, E-mail: kawanisi@suzuka-u.ac.jp [Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie (Japan); Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie (Japan)

    2011-10-22

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

  1. Stage of urinary bladder cancer at first presentation

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    Al-Bazzaz Pishtewan

    2009-01-01

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

  2. EZH2 in Bladder Cancer, a Promising Therapeutic Target

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    Mónica Martínez-Fernández

    2015-11-01

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

  3. 人膀胱癌裸鼠原位移植瘤动物模型的建立和MRI检测%Establishment of orthotopic transplantation model of human bladder cancer and detection by MRT

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective:To establish an orthotopic bladder cancer model bearing human bladder cancer for experimental research, and monitor tumor progression by magnetic resonance imaging (MRI). Methods: The mucosa was mechanically damaged transurethrally under direct vision, and then human bladder cancer cell line T24 was inoculated into the bladders of BALB/c nude mice to establish orthotopic bladder cancer model. To find a suitable concentration of Gd-DTPA for this research. MRI was performed weekly to assess tumor growth, using Gd-DTPA as contrast agent. The pathologic morphology of the bladders and other specimens were observed with HE stain. Results: All the 25 mice developed bladder cancer after inoculation. The best concentration of Gd-DTPAwas 1.408 mg/mL. On MRI, no change in the bladders was observed on day 7 after inoculation, filling defect in the bladders, accordant to actual tumor size, was detected on days 14, 21 and 28. Pathologic examination showed that tumor grew in the mucosa or superficial muscle of bladder on day 7, confined in muscle layer on days 14-28, and invaded serosa on day 35. Conclusion: Transurethrally damaged bladder mucosa under direct vision and instilled bladder cancer cell T24, we successfully established an orthotopic bladder cancer model. Tumor growth simulated the progression of human bladder cancer approximately. MRI was a reliable way for dynamic detection of murine orthotopic bladder tumor.

  4. The Immediate Results of Surgical Treatment of Bladder Cancer

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    Alexei L. Charyshkin

    2016-06-01

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

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

    Science.gov (United States)

    Bouchelouche, Kirsten; Choyke, Peter L

    2015-07-01

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

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

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    Ganglong Yang

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

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

    Science.gov (United States)

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

    2008-01-01

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

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

    DEFF Research Database (Denmark)

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

    1995-01-01

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

  9. Multifunctional targeting micelle nanocarriers with both imaging and therapeutic potential for bladder cancer

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    Lin TY

    2012-06-01

    Full Text Available Tzu-yin Lin,1 Hongyong Zhang,1 Juntao Luo,2,5 Yuanpei Li,2 Tingjuan Gao,3 Primo N Lara Jr,1,4,6 Ralph de Vere White,4 Kit S Lam,1,2 Chong-Xian Pan,1,3,61Division of Hematology and Oncology, Department of Internal Medicine, 2Department of Biochemistry and Molecular Medicine, 3NSF Center for Biophotonics Science and Technology, School of Medicine, 4Department of Urology, University of California-Davis, Sacramento, CA, 5Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, 6VA Northern California Health Care System, Mather, CA, USABackground: We previously developed a bladder cancer-specific ligand (PLZ4 that can specifically bind to both human and dog bladder cancer cells in vitro and in vivo. We have also developed a micelle nanocarrier drug-delivery system. Here, we assessed whether the targeting micelles decorated with PLZ4 on the surface could specifically target dog bladder cancer cells.Materials and methods: Micelle-building monomers (ie, telodendrimers were synthesized through conjugation of polyethylene glycol with a cholic acid cluster at one end and PLZ4 at the other, which then self-assembled in an aqueous solution to form micelles. Dog bladder cancer cell lines were used for in vitro and in vivo drug delivery studies.Results: Compared to nontargeting micelles, targeting PLZ4 micelles (23.2 ± 8.1 nm in diameter loaded with the imaging agent DiD and the chemotherapeutic drug paclitaxel or daunorubicin were more efficient in targeted drug delivery and more effective in cell killing in vitro. PLZ4 facilitated the uptake of micelles together with the cargo load into the target cells. We also developed an orthotopic invasive dog bladder cancer xenograft model in mice. In vivo studies with this model showed the targeting micelles were more efficient in targeted drug delivery than the free dye (14.3×; P < 0.01 and nontargeting micelles (1.5×; P < 0.05.Conclusion: Targeting micelles decorated with PLZ4 can selectively

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

    Science.gov (United States)

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

    2014-02-28

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

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

    Science.gov (United States)

    Spradling, Kyle; Youssef, Ramy F

    2016-03-15

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

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

    Science.gov (United States)

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

    2016-02-01

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

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

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    T. Salman

    1996-01-01

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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    Science.gov (United States)

    Miyakawa, M; Yoshida, O

    1989-12-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

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

  17. The present and future burden of urinary bladder cancer in the world.

    NARCIS (Netherlands)

    Ploeg, M.; Aben, K.K.H.; Kiemeney, L.A.L.M.

    2009-01-01

    Urinary bladder cancer (UBC) is a common disease worldwide. At any point in time 2.7 million people have a history of UBC. The incidence of UBC varies over the world with highest rates in developed communities. But the burden of UBC will increase in less developed areas of the world. These changes c

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

    Directory of Open Access Journals (Sweden)

    Joshua B. Kaelberer

    2016-09-01

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

  19. Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Kari T. Syvänen

    2014-05-01

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

  20. Organ-sparing treatment of advanced bladder cancer. Paclitaxel as a radiosensitizer

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, A.C. [Halle Univ. (Germany). Dept. of Radiation Oncology; Tuebingen Univ. (Germany). Dept. of Radiooncology; Diestelhorst, A.; Kuhnt, T. [Halle Univ. (Germany). Dept. of Radiation Oncology; Kuehn, R. [Martha Maria Hospital Halle (Germany). Dept. of Urology; Fornara, P. [Halle Univ. (Germany). Dept. of Urology; Scholz, H.J. [Asklepios Hospital Weissenfels (Germany). Dept. of Urology; Dunst, J. [Halle Univ. (Germany). Dept. of Radiation Oncology; Luebeck Univ. (Germany). Dept. of Radiation Oncology; Zietman, A.L. [Massachusetts General Hospital, Boston, MA (United States). Dept. of Radiation Oncology

    2007-04-15

    Background and Purpose: Transurethral resection of bladder tumor (TUR-BT) and radiochemotherapy with cisplatin achieve high rates of bladder preservation and survival figures identical to radical cystectomy in muscle-invasive bladder cancers. The authors have investigated the potential use of paclitaxel in a radiochemotherapy protocol for patients with inoperable bladder carcinomas and mainly contraindications to cisplatin. Patients and Methods: Between October 1997 to August 2004, 42 patients (median age 71 years) suffering from muscle-invasive (n = 32) or recurrent (n = 10) bladder cancers were treated with a paclitaxel-containing radiochemotherapy (paclitaxel 25-35 mg/m2 twice weekly) after TUR-BT (R0/1/2/x in n = 18/4/14/3) or cystectomy with residual tumor (n = 3). Five patients received additional cisplatin. Radiation treatment was administered to a total dose of 45-60 Gy. Results: 76.2% completed the planned regimen. Adaptations of treatment were mainly required due to diarrhea. Grade 3/4 toxicities occurred in 15/1 patients. Severe renal toxicities did not occur. 28 patients underwent restaging TUR-BT 6 weeks after radiochemotherapy (complete remission/partial remission/progressive disease: n = 24/3/1). Three patients developed a local recurrence and four distant metastases. Seven patients died from tumor, six of other reasons. Conclusion: Radiochemotherapy with paclitaxel was feasible and this bladder approach needs further investigation to evaluate whether paclitaxel could become a substitute for cisplatin.

  1. Mechanism responsible for the antitumor effect of BCG-CWS using the LEEL method in a mouse bladder cancer model.

    Science.gov (United States)

    Nakamura, Takashi; Fukiage, Masafumi; Suzuki, Yoshiteru; Yano, Ikuya; Miyazaki, Jun; Nishiyama, Hiroyuki; Akaza, Hideyuki; Harashima, Hideyoshi

    2014-12-28

    We previously reported on the development of a water soluble formulation of the cell wall skeleton of BCG (BCG-CWS), a major immune active center of BCG, by encapsulating it into a nanoparticle (CWS-NP). The CWS-NP allowed us to clarify the machinery associated with the BCG mediated anti-bladder tumor effect, especially the roles of bladder cancer cells and dendritic cells (DCs) in the initial step, which remains poorly understood. We show herein that the internalization of BCG-CWS by bladder cancer cells, but not DCs, is indispensable for the induction of an antitumor effect against bladder cancer. Tumor growth was significantly inhibited in mice that had been inoculated with mouse bladder cancer (MBT-2) cells containing internalized BCG-CWS. On the other hand, the internalization of BCG-CWS by DCs had only a minor effect on inducing an antitumor effect against MBT-2 tumors. This was clarified for the first time by using the CWS-NP. This finding provides insights into our understanding of the role of bladder cancer cells and DCs in BCG therapy against bladder cancer.

  2. Bladder Diseases

    Science.gov (United States)

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

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

    Directory of Open Access Journals (Sweden)

    Saika T

    2003-12-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  5. Preclinical dosimetry of magnetic fluid hyperthermia for bladder cancer

    Science.gov (United States)

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

    2013-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Mei-Yueh Lee

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

  7. A comparison of three different adaptive strategies in image-guided radiotherapy of bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Vestergaard, Anne; Soendergaard, Jimmi; Petersen, Joergen B. (Dept. of Medical Physics, Aarhus Univ. Hospital, Noerrebrogade 44, DK-8000 Aarhus C (Denmark)), E-mail: annveste@rm.dk; Hoeyer, Morten; Muren, Ludvig Paul (Dept. of Oncology, Aarhus Univ. Hospital, Noerrebrogade 44, DK-8000 Aarhus C (Denmark))

    2010-10-15

    The urinary bladder shows considerable individual variation in shape and position during a course of radiotherapy (RT). In this study we have developed and compared three different adaptive RT (ART) strategies for bladder cancer involving daily cone beam CT (CBCT) imaging and plan selection. Material and methods. Ten patients treated for bladder cancer had daily CBCTs acquired that were registered online using bony anatomy registration. Seven patients received intensity modulated RT (IMRT) with a simultaneous integrated boost (SIB) technique to the bladder and pelvic lymph nodes. Three patients received treatment to the bladder only. Retrospectively, we compared three ART strategies that were all based on daily selection of the most suitable plan from a library consisting of three IMRT-plans corresponding to a small, medium and large target volume. ART method A utilised population-based margins while methods B and C used the bladder as seen on CBCT-scans from the first week of treatment; method B without delineation of the bladder on CBCT and method C with delineation of the bladder. Total dose distributions were calculated using the planning CT. For each patient, we calculated ratios of the dose volume histograms (DVHs) for the three ART strategies relative to non-adaptive therapy. Results. The inter-patient variation was large for all three ART strategies. The mean ratios of the volumes receiving 57 Gy or more (corresponding to 95% of prescribed dose) for methods A, B and C were 0.66 (SD: 0.11), 0.67 (SD: 0.13) and 0.67 (SD: 0.16) respectively when compared to the non-adaptive plan. Conclusion. When using any of the ART strategies, it is possible to reduce significantly the volumes receiving high doses compared to the use of a standard non-adaptive plan. The differences in dose volume parameters between the three methods were small compared with the differences from the standard plan.

  8. Urine Telomerase for Diagnosis and Surveillance of Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Angela Lamarca

    2012-01-01

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

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

    Science.gov (United States)

    Smolensky, Dmitriy; Rathore, Kusum; Cekanova, Maria

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yong-tong Zhu

    2014-07-01

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

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

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    Carmen J Marsit

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

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

    Science.gov (United States)

    Whitmore, W F; Batata, M

    1984-11-01

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

  13. Epidemiology and risk factors of urothelial bladder cancer

    NARCIS (Netherlands)

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

    2013-01-01

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

  14. Use of thiazolidinediones and risk of bladder cancer

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    NARCIS (Netherlands)

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

    2005-01-01

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

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

    NARCIS (Netherlands)

    Grimbergen, M.C.M.

    2010-01-01

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

  17. Elevated connexin 43 expression in arsenite-and cadmium-transformed human bladder cancer cells, tumor transplants and selected high grade human bladder cancers.

    Science.gov (United States)

    Zhang, Ruowen; Wang, Liping; Garrett, Scott H; Sens, Donald A; Dunlevy, Jane R; Zhou, Xu Dong; Somji, Seema

    2016-10-01

    Connexin 43 has been shown to play a role in cell migration and invasion; however, its role in bladder cancer is not well defined. Previous studies from our laboratory have shown that the environmental pollutants arsenite and cadmium can cause malignant transformation of the immortalized urothelial cell line UROtsa. These transformed cells can form tumors in immune-compromised mice. The goal of the present study was to determine if connexin 43 is expressed in the normal human bladder, the arsenite and cadmiun-transformed UROtsa cells as well as human urothelial cancer. The results obtained showed that connexin 43 is not expressed in the epithelial cells of the human bladder but is expressed in immortalized cultures of human urothelial cells and the expression is variable in the arsenite and cadmium- transformed urothelial cell lines derived from these immortalized cells. Tumor heterotransplants generated from the transformed cells expressed connexin 43 and the expression was localized to areas of squamous differentiation. Immuno-histochemical analysis of human bladder cancers also showed that the expression of connexin 43 was localized to areas of the tumor that showed early features of squamous differentiation. Treatment of UROtsa cells with various concentrations of arsenite or cadmium did not significantly alter the expression level of connexin 43. In conclusion, our results show that the expression of connexin 43 is localized to the areas of the tumor that show squamous differentiation, which may be an indicator of poor prognosis. This suggests that connexin 43 has the potential to be developed as a biomarker for bladder cancer that may have the ability to invade and metastasize.

  18. Recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Zieger, Karsten; Ørntoft, Torben Falck

    2007-01-01

    individually contributed to the management of the disease. However, the development of high-throughput techniques for simultaneous assessment of a large number of markers has allowed classification of tumors into clinically relevant molecular subgroups beyond those possible by pathological classification. Here......, we review the recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers....

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-12-15

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

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

    Science.gov (United States)

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

    1998-04-01

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

  1. Improvement of the cytological diagnosis of bladder cancer

    Directory of Open Access Journals (Sweden)

    M. G. Leonov

    2014-12-01

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

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

    OpenAIRE

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

    2010-01-01

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

  3. Bladder Cancer in an Inguinoscrotal Vesical Hernia

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    Lucas Regis

    2012-01-01

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

  4. Prima-1 induces apoptosis in bladder cancer cell lines by activating p53

    Directory of Open Access Journals (Sweden)

    Camila B. Piantino

    2013-01-01

    Full Text Available OBJECTIVES: Bladder cancer represents 3% of all carcinomas in the Brazilian population and ranks second in incidence among urological tumors, after prostate cancer. The loss of p53 function is the main genetic alteration related to the development of high-grade muscle-invasive disease. Prima-1 is a small molecule that restores tumor suppressor function to mutant p53 and induces cancer cell death in various cancer types. Our aim was to investigate the ability of Prima-1 to induce apoptosis after DNA damage in bladder cancer cell lines. METHOD: The therapeutic effect of Prima-1 was studied in two bladder cancer cell lines: T24, which is characterized by a p53 mutation, and RT4, which is the wild-type for the p53 gene. Morphological features of apoptosis induced by p53, including mitochondrial membrane potential changes and the expression of thirteen genes involved in apoptosis, were assessed by microscopic observation and quantitative real-time PCR (qRT-PCR. RESULTS: Prima-1 was able to reactivate p53 function in the T24 (p53 mt bladder cancer cell line and promote apoptosis via the induction of Bax and Puma expression, activation of the caspase cascade and disruption of the mitochondrial membrane in a BAK-independent manner. CONCLUSION: Prima-1 is able to restore the transcriptional activity of p53. Experimental studies in vivo may be conducted to test this molecule as a new therapeutic agent for urothelial carcinomas of the bladder, which characteristically harbor p53 mutations.

  5. Meloxicam in the treatment of in vitro and in vivo models of urinary bladder cancer.

    Science.gov (United States)

    Arantes-Rodrigues, Regina; Pinto-Leite, Rosário; Ferreira, Rita; Neuparth, Maria João; Pires, Maria João; Gaivão, Isabel; Palmeira, Carlos; Santos, Lúcio; Colaço, Aura; Oliveira, Paula

    2013-05-01

    To assess the efficacy of meloxicam, a non-steroidal anti-inflammatory drug (NSAID), on three human urinary bladder-cancer cell lines (HT1376, T24 and 5637) and on mice urinary bladder cancer chemically induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). The in vitro effects of meloxicam were assessed by optical microscopy, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method, flow cytometry and comet assay. In vivo, Hsd:ICR male mice were exposed to BBN in drinking water, over the course of 12 weeks. Subsequently, animals were treated with meloxicam by intraperitoneal route, for 6 consecutively weeks. Tumour development was evaluated by haematoxylin and eosin staining. Renal and hepatic functions, interleucin-6 (IL-6), C-reactive protein (CRP) and tumour necrosis factor (TNFα) were also evaluated. In vitro, meloxicam induced a significant (Pmeloxicam-treated cells. In vivo, the incidence of pre-neoplastic lesions induced by BBN was not affected by meloxicam treatment. However, although not statistically significant, the development of neoplastic lesions was inhibited by meloxicam treatment without significant alterations of renal or hepatic parameters. Meloxicam is effective on in vitro and in vivo models of urinary bladder cancer. These findings support that meloxicam deserves more attention on urinary bladder cancer study.

  6. Laparoscopic partial cystectomy for urachal and bladder cancer

    Directory of Open Access Journals (Sweden)

    Jose R. Colombo Jr.

    2008-01-01

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

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

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    Bishop D Timothy

    2008-07-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

  9. Disulfide-crosslinked nanomicelles confer cancer-specific drug delivery and improve efficacy of paclitaxel in bladder cancer

    Science.gov (United States)

    Pan, Amy; Zhang, Hongyong; Li, Yuanpei; Lin, Tzu-yin; Wang, Fuli; Lee, Joyce; Cheng, Mingshan; Dall'Era, Marc; Li, Tianhong; deVere White, Ralph; Pan, Chong-Xian; Lam, Kit S.

    2016-10-01

    Chemotherapy commonly used in the treatment of advanced bladder cancer is only moderately effective and associated with significant toxicity. There has been no appreciable improvement in overall survival over the last three decades. The goal of this project is to develop and characterize bladder cancer-specific nanometer-scale micelles loaded with the chemotherapeutic drug paclitaxel (PTX) and determine the anti-tumor activity and toxicity. Micelle-building-material telodendrimers were synthesized through the stepwise conjugation of eight cholic acid units at one terminus of polyethylene glycol (PEG) and a bladder cancer-specific targeting peptide named PLZ4 at the other terminus. To synthesize disulfide-crosslinked PLZ4 nanomicelles (DC-PNM), cysteine was introduced between the cholic acid and PEG. DC-PNM-PTX was synthesized through the evaporation method by loading PTX in the core. The loading capacity of PTX in DC-PNM was 25% (W/W). The loading efficiency was over 99%. DC-PNM-PTX was spherical with the median size of 25 nm. The stability of DC-PNM-PTX was determined in a solution containing sodium docecyl sulfate (SDS). It was stable in a SDS solution, but dissolved within 5 min after the addition of glutathione at the physiological intracellular concentration of 10 mM. In vivo targeting and anti-tumor activity were determined in immunodeficient mice carrying patient-derived bladder cancer xenografts (PDXs). After intravenous administration, DC-PNM specifically targeted the bladder cancer PDXs, but very little to the lung cancer xenografts in the same mice (p cancer xenografts in vivo, and improved the anti-cancer efficacy of PTX.

  10. Summary and Recommendations from the National Cancer Institute’s Clinical Trials Planning Meeting on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer

    Science.gov (United States)

    Lerner, Seth P.; Bajorin, Dean F.; Dinney, Colin P.; Efstathiou, Jason A.; Groshen, Susan; Hahn, Noah M.; Hansel, Donna; Kwiatkowski, David; O’Donnell, Michael; Rosenberg, Jonathan; Svatek, Robert; Abrams, Jeffrey S.; Al-Ahmadie, Hikmat; Apolo, Andrea B.; Bellmunt, Joaquim; Callahan, Margaret; Cha, Eugene K.; Drake, Charles; Jarow, Jonathan; Kamat, Ashish; Kim, William; Knowles, Margaret; Mann, Bhupinder; Marchionni, Luigi; McConkey, David; McShane, Lisa; Ramirez, Nilsa; Sharabi, Andrew; Sharpe, Arlene H.; Solit, David; Tangen, Catherine M.; Amiri, Abdul Tawab; Van Allen, Eliezer; West, Pamela J.; Witjes, J. A.; Quale, Diane Zipursky

    2016-01-01

    The NCI Bladder Cancer Task Force convened a Clinical Trials Planning Meeting (CTPM) Workshop focused on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer (NMIBC). Meeting attendees included a broad and multi-disciplinary group of clinical and research stakeholders and included leaders from NCI, FDA, National Clinical Trials Network (NCTN), advocacy and the pharmaceutical and biotech industry. The meeting goals and objectives were to: 1) create a collaborative environment in which the greater bladder research community can pursue future optimally designed novel clinical trials focused on the theme of molecular targeted and immune-based therapies in NMIBC; 2) frame the clinical and translational questions that are of highest priority; and 3) develop two clinical trial designs focusing on immunotherapy and molecular targeted therapy. Despite successful development and implementation of large Phase II and Phase III trials in bladder and upper urinary tract cancers, there are no active and accruing trials in the NMIBC space within the NCTN. Disappointingly, there has been only one new FDA approved drug (Valrubicin) in any bladder cancer disease state since 1998. Although genomic-based data for bladder cancer are increasingly available, translating these discoveries into practice changing treatment is still to come. Recently, major efforts in defining the genomic characteristics of NMIBC have been achieved. Aligned with these data is the growing number of targeted therapy agents approved and/or in development in other organ site cancers and the multiple similarities of bladder cancer with molecular subtypes in these other cancers. Additionally, although bladder cancer is one of the more immunogenic tumors, some tumors have the ability to attenuate or eliminate host immune responses. Two trial concepts emerged from the meeting including a window of opportunity trial (Phase 0) testing an FGFR3 inhibitor and a second multi-arm multi-stage trial testing combinations

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

    Directory of Open Access Journals (Sweden)

    Wei Qiu

    2017-03-01

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

  12. Organic cation secretion by Cancer borealis urinary bladder

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    Geller, Frank; Urfer, Wolfgang; Golka, Klaus

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Carrie A. Franzen

    2014-01-01

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

  15. Natural biology and management of nonmuscle invasive bladder cancer

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    1981-02-15

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

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

    Directory of Open Access Journals (Sweden)

    Ufuoma Miller Fakpor

    2016-10-01

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

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

    DEFF Research Database (Denmark)

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

    2000-01-01

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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    Science.gov (United States)

    Price, G E

    1994-03-01

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

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

    Science.gov (United States)

    Skinner, Eila C

    2016-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

  3. Pioglitazone use and the risk of bladder cancer.

    Science.gov (United States)

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

    2014-02-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Muren, Ludvig PAul

    2002-07-01

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

  5. Marker evaluation of human breast and bladder cancers

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-11-02

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

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

    Science.gov (United States)

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

    2013-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Daniel Y.C. Heng

    2011-12-01

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

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

    Institute of Scientific and Technical Information of China (English)

    白银; 王琰; 周丽君; 俞莉章

    2001-01-01

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

  9. Combined systemic therapy and radiotherapy for bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Roedel, C.; Weiss, C. [Dept. of Radiotherapy and Oncology, Univ. of Frankfurt (Germany); Sauer, R. [Dept. of Radiotherapy, Univ. of Erlangen (Germany)

    2007-12-15

    The standard of care for transitional-cell carcinoma of the bladder with invasion to the muscularis propria is radical cystectomy. Sophisticated techniques for urinary diversion have been developed to improve patients' quality of life. Even the construction of a neobladder with continent urinary diversion, however, cannot substitute for the patient's original bladder. Attempts to obtain organ preservation are only justified when they have a high likelihood of achieving local cure with no compromise in survival rates. Adequate local control cannot be achieved with transurethral resection of the bladder tumor (TURBT), chemotherapy, or radiotherapy, when used alone. Several groups have reported the value of combining all three modalities, with salvage cystectomy being reserved for patients with incomplete response or local relapse. (orig.)

  10. Malakoplakia mimics urinary bladder cancer: A case report

    Directory of Open Access Journals (Sweden)

    Ristić-Petrović Ana

    2013-01-01

    Full Text Available Introduction. Malakoplakia is an unusual and very rare chronic inflammatory disease. In bladder especially it can mimic malignancy and lead to serious misdiagnosis. Case report. We presented a case of a middle-aged woman with persistent macrohematuria and cystoscopically polypoid bladder mass that resembled a neoplastic process. The final diagnosis was based on cystoscopic biopsy and microscopic findings of acidophilic, foamy histiocytes with the presence of Michaelis-Gutmann inclusions which are characteristic for diagnosis of malakoplakia. Immunohistochemistry confirmed diagnosis by demonstrating CD68-positive macrophages. Conclusion. Urinary bladder malakoplakia should be considered in patients with persistent urinary tract infections and tumor mass at cystoscopy. Early identification with prompt antibiotic treatment can be helpful in avoiding unnecessary surgical interventions and in preventing development of possible complications. [Projekat Ministarstva nauke Republike Srbije, br. 175092

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

    Energy Technology Data Exchange (ETDEWEB)

    Conde, Vanessa R. [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Oliveira, Pedro F. [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Department of Microscopy, Laboratory of Cell Biology and Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto – UMIB/ICBAS/UP (Portugal); Nunes, Ana R.; Rocha, Cátia S. [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Ramalhosa, Elsa; Pereira, José A. [Mountain Research Centre (CIMO), School of Agriculture, Polytechnic Institute of Bragança (Portugal); Alves, Marco G., E-mail: alvesmarc@gmail.com [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Silva, Branca M., E-mail: bmcms@ubi.pt [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal)

    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.

  12. Expression of p53 family genes in urinary bladder cancer: correlation with disease aggressiveness and recurrence.

    Science.gov (United States)

    Papadogianni, Danae; Soulitzis, Nikolaos; Delakas, Demetrios; Spandidos, Demetrios A

    2014-03-01

    p53 is a tumour suppressor gene with an established role in the majority of human neoplasias. Its homologues-p63 and p73-cannot be classified as tumour suppressors, since they encode isoforms with oncogenic properties as well. p63 plays a crucial role in epithelial cell differentiation and p73 is essential for neuronal cell development. The p63 and p73 expressions have been investigated in a variety of human tumours including bladder carcinomas; yet, this is the first study to simultaneously analyse the transcriptional levels of all p53 family members in bladder cancer. Using quantitative real-time polymerase chain reaction, we measured the mRNA expression of p53, p63 and p73 in 30 bladder tumours, each paired with adjacent normal tissue. All three studied genes were up-regulated in malignant specimens, p53 by 1.9-fold, p63 by threefold and p73 by twofold, respectively. Further analysis suggested that p63 and p73 act independently of p53 in the malignant bladder epithelium. Statistical analysis revealed that p63 overexpression was more frequent in recurrent bladder tumours (p = 0.045) and in older patients (p = 0.022). Papillary tumours also exhibited abnormal p63 expression (p = 0.026). Finally, p73 was up-regulated in Grade III one-site tumours (p = 0.040). Our results indicate that all p53 family members are abnormally expressed in bladder cancer but do not act synergistically. High levels of p63 correlate with non-muscle invasive tumours with frequent relapses, whereas p73 overexpression is associated with a more aggressive tumour phenotype.

  13. Treatment Options by Stage (Bladder Cancer)

    Science.gov (United States)

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

  14. Screening for Bladder and Other Urothelial Cancers

    Science.gov (United States)

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

  15. Management of Bladder Cancer following Solid Organ Transplantation

    Directory of Open Access Journals (Sweden)

    Jeffrey J. Tomaszewski

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jasmina Makarević

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Montserrat García-Closas

    2007-02-01

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

  19. Photodynamic therapy in the prophylactic management of bladder cancer

    Science.gov (United States)

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

    1991-06-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

    Shahait, Mohammed; Bulbul, Muhammad

    2016-10-27

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2008-04-01

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

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

    Science.gov (United States)

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

    2007-01-01

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

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

    LENUS (Irish Health Repository)

    Fanning, D M

    2009-03-18

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

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

    LENUS (Irish Health Repository)

    Fanning, D M

    2012-02-01

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

  7. Loss of the urothelial differentiation marker FOXA1 is associated with high grade, late stage bladder cancer and increased tumor proliferation.

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    David J DeGraff

    Full Text Available Approximately 50% of patients with muscle-invasive bladder cancer (MIBC develop metastatic disease, which is almost invariably lethal. However, our understanding of pathways that drive aggressive behavior of MIBC is incomplete. Members of the FOXA subfamily of transcription factors are implicated in normal urogenital development and urologic malignancies. FOXA proteins are implicated in normal urothelial differentiation, but their role in bladder cancer is unknown. We examined FOXA expression in commonly used in vitro models of bladder cancer and in human bladder cancer specimens, and used a novel in vivo tissue recombination system to determine the functional significance of FOXA1 expression in bladder cancer. Logistic regression analysis showed decreased FOXA1 expression is associated with increasing tumor stage (p<0.001, and loss of FOXA1 is associated with high histologic grade (p<0.001. Also, we found that bladder urothelium that has undergone keratinizing squamous metaplasia, a precursor to the development of squamous cell carcinoma (SCC exhibited loss of FOXA1 expression. Furthermore, 81% of cases of SCC of the bladder were negative for FOXA1 staining compared to only 40% of urothelial cell carcinomas. In addition, we showed that a subpopulation of FOXA1 negative urothelial tumor cells are highly proliferative. Knockdown of FOXA1 in RT4 bladder cancer cells resulted in increased expression of UPK1B, UPK2, UPK3A, and UPK3B, decreased E-cadherin expression and significantly increased cell proliferation, while overexpression of FOXA1 in T24 cells increased E-cadherin expression and significantly decreased cell growth and invasion. In vivo recombination of bladder cancer cells engineered to exhibit reduced FOXA1 expression with embryonic rat bladder mesenchyme and subsequent renal capsule engraftment resulted in enhanced tumor proliferation. These findings provide the first evidence linking loss of FOXA1 expression with histological subtypes

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

    Science.gov (United States)

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

    2017-02-15

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Science.gov (United States)

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

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

    Directory of Open Access Journals (Sweden)

    Goossens Maria E

    2012-03-01

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

  13. Null mutation for Macrophage Migration Inhibitory Factor (MIF is associated with less aggressive bladder cancer in mice

    Directory of Open Access Journals (Sweden)

    Tsimikas John

    2007-07-01

    Full Text Available Abstract Background Inflammatory cytokines may promote tumorigenesis. Macrophage migration inhibitory factor (MIF is a proinflammatory cytokine with regulatory properties over tumor suppressor proteins involved in bladder cancer. We studied the development of bladder cancer in wild type (WT and MIF knockout (KO mice given N-butyl-N-(4-hydroxybutyl-nitrosamine (BBN, a known carcinogen, to determine the role of MIF in bladder cancer initiation and progression. Methods 5-month old male C57Bl/6 MIF WT and KO mice were treated with and without BBN. Animals were sacrificed at intervals up to 23 weeks of treatment. Bladder tumor stage and grade were evaluated by H&E. Immunohistochemical (IHC analysis was performed for MIF and platelet/endothelial cell adhesion molecule 1 (PECAM-1, a measure of vascularization. MIF mRNA was analyzed by quantitative real-time polymerase chain reaction. Results Poorly differentiated carcinoma developed in all BBN treated mice by week 20. MIF WT animals developed T2 disease, while KO animals developed only T1 disease. MIF IHC revealed predominantly urothelial cytoplasmic staining in the WT control animals and a shift toward nuclear staining in WT BBN treated animals. MIF mRNA levels were 3-fold higher in BBN treated animals relative to controls when invasive cancer was present. PECAM-1 staining revealed significantly more stromal vessels in the tumors in WT animals when compared to KOs. Conclusion Muscle invasive bladder cancer with increased stromal vascularity was associated with increased MIF mRNA levels and nuclear redistribution. Consistently lower stage tumors were seen in MIF KO compared to WT mice. These data suggest that MIF may play a role in the progression to invasive bladder cancer.

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

    Science.gov (United States)

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

    2014-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Young-Goo Lee

    2002-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Science.gov (United States)

    Yamamura, J

    1989-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-10-15

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

  19. MicroRNA expression signatures of bladder cancer revealed by deep sequencing.

    Directory of Open Access Journals (Sweden)

    Yonghua Han

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are a class of small noncoding RNAs that regulate gene expression. They are aberrantly expressed in many types of cancers. In this study, we determined the genome-wide miRNA profiles in bladder urothelial carcinoma by deep sequencing. METHODOLOGY/PRINCIPAL FINDINGS: We detected 656 differentially expressed known human miRNAs and miRNA antisense sequences (miRNA*s in nine bladder urothelial carcinoma patients by deep sequencing. Many miRNAs and miRNA*s were significantly upregulated or downregulated in bladder urothelial carcinoma compared to matched histologically normal urothelium. hsa-miR-96 was the most significantly upregulated miRNA and hsa-miR-490-5p was the most significantly downregulated one. Upregulated miRNAs were more common than downregulated ones. The hsa-miR-183, hsa-miR-200b ∼ 429, hsa-miR-200c ∼ 141 and hsa-miR-17 ∼ 92 clusters were significantly upregulated. The hsa-miR-143 ∼ 145 cluster was significantly downregulated. hsa-miR-182, hsa-miR-183, hsa-miR-200a, hsa-miR-143 and hsa-miR-195 were evaluated by Real-Time qPCR in a total of fifty-one bladder urothelial carcinoma patients. They were aberrantly expressed in bladder urothelial carcinoma compared to matched histologically normal urothelium (p < 0.001 for each miRNA. CONCLUSIONS/SIGNIFICANCE: To date, this is the first study to determine genome-wide miRNA expression patterns in human bladder urothelial carcinoma by deep sequencing. We found that a collection of miRNAs were aberrantly expressed in bladder urothelial carcinoma compared to matched histologically normal urothelium, suggesting that they might play roles as oncogenes or tumor suppressors in the development and/or progression of this cancer. Our data provide novel insights into cancer biology.

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

    Science.gov (United States)

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

    1977-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Maurice M Garcia

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

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

    Science.gov (United States)

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

    2016-02-01

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

  3. Control over structure-specific flexibility improves anatomical accuracy for point-based deformable registration in bladder cancer radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Wognum, S.; Chai, X.; Hulshof, M. C. C. M.; Bel, A. [Department of Radiotherapy, Academic Medical Center, Meiberdreef 9, 1105 AZ Amsterdam (Netherlands); Bondar, L.; Zolnay, A. G.; Hoogeman, M. S. [Department of Radiation Oncology, Daniel den Hoed Cancer Center, Erasmus Medical Center, Groene Hilledijk 301, 3075 EA Rotterdam (Netherlands)

    2013-02-15

    Purpose: Future developments in image guided adaptive radiotherapy (IGART) for bladder cancer require accurate deformable image registration techniques for the precise assessment of tumor and bladder motion and deformation that occur as a result of large bladder volume changes during the course of radiotherapy treatment. The aim was to employ an extended version of a point-based deformable registration algorithm that allows control over tissue-specific flexibility in combination with the authors' unique patient dataset, in order to overcome two major challenges of bladder cancer registration, i.e., the difficulty in accounting for the difference in flexibility between the bladder wall and tumor and the lack of visible anatomical landmarks for validation. Methods: The registration algorithm used in the current study is an extension of the symmetric-thin plate splines-robust point matching (S-TPS-RPM) algorithm, a symmetric feature-based registration method. The S-TPS-RPM algorithm has been previously extended to allow control over the degree of flexibility of different structures via a weight parameter. The extended weighted S-TPS-RPM algorithm was tested and validated on CT data (planning- and four to five repeat-CTs) of five urinary bladder cancer patients who received lipiodol injections before radiotherapy. The performance of the weighted S-TPS-RPM method, applied to bladder and tumor structures simultaneously, was compared with a previous version of the S-TPS-RPM algorithm applied to bladder wall structure alone and with a simultaneous nonweighted S-TPS-RPM registration of the bladder and tumor structures. Performance was assessed in terms of anatomical and geometric accuracy. The anatomical accuracy was calculated as the residual distance error (RDE) of the lipiodol markers and the geometric accuracy was determined by the surface distance, surface coverage, and inverse consistency errors. Optimal parameter values for the flexibility and bladder weight

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

    Science.gov (United States)

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

    2014-01-01

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

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

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    Júlio Santos

    2014-12-01

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

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

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    Goldberg José

    2008-08-01

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

  7. A departmental audit of patients with bladder cancer.

    Science.gov (United States)

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

    1992-01-01

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

  8. Occupation and Risk of Bladder Cancer in Nordic Countries

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

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    Oliveira Paula A

    2009-01-01

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

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

    Science.gov (United States)

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

    2013-10-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-02-01

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

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

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    Noâma Berrada

    2013-01-01

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

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

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    Guadalupe Lorenzatti Hiles

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

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

    Science.gov (United States)

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

    2016-09-02

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

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

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    Evanguelos Xylinas

    2016-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-12-15

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  19. Developing a functional urinary bladder: a neuronal context

    Directory of Open Access Journals (Sweden)

    Janet R Keast

    2015-09-01

    Full Text Available The development of organs occurs in parallel with the formation of their nerve supply. The innervation of pelvic organs (lower urinary tract, hindgut, and sexual organs is complex and we know remarkably little about the mechanisms that form these neural pathways. The goal of this short review is to use the urinary bladder as an example to stimulate interest in this question. The bladder requires a healthy mature nervous system to store urine and release it at behaviourally appropriate times. Understanding the mechanisms underlying the construction of these neural circuits is not only relevant to defining the basis of developmental problems but may also suggest strategies to restore connectivity and function following injury or disease in adults. The bladder nerve supply comprises multiple classes of sensory, and parasympathetic or sympathetic autonomic effector (motor neurons. First, we define the developmental endpoint by describing this circuitry in adult rodents. Next we discuss the innervation of the developing bladder, identifying challenges posed by this area of research. Last we provide examples of genetically modified mice with bladder dysfunction and suggest potential neural contributors to this state.

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

    Science.gov (United States)

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

    2016-02-01

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

  1. Robotic Radical Cystectomy for Bladder Cancer: Current Perspectives

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    Abdullah Erdem Canda

    2014-05-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-02-01

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

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

    Science.gov (United States)

    Yeung, Christina; Dinh, Tuan; Lee, Joseph

    2014-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Cheryl Shih

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Quirk Jeffrey T

    2004-09-01

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

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

    Directory of Open Access Journals (Sweden)

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

    2008-12-01

    Full Text Available Background: Urinary bladder cancer is one of the major health problem all over the world. Cystoscopy remains the gold standard for identifying bladder cancer but it is invasive and expensive, therefore, a simple, non invasive test for detecting bladder cancer would be helpful. Several biomarkers for bladder cancer have been used, but no single marker has been accurate and conclusive. Aim: The current study aimed to measure telomerase enzyme in urine as a useful non invasive marker for detection of bladder cancer. Methods : Forty eight patients ( 39 males and 9 females were included, They are complaining of urinary symptoms and undergo cystoscopy with biopsy of bladder lesions and histopathological examination. They were divided into groups: Group I: 16 patients ( 11 males and 5 females have benign urologic conditions. Group II: 32 patients (28 males and 4 females have proven bladder cancer patients underwent transurethral resection of bladder tumor or cystoscopy with biopsy of bladder lesions. Also, 15 apparently healthy volunteers with matched age and sex with patients were served as a control group. All subjects were submitted to laboratory estimation of the following in urine: urinary creatinine, urine cytology, telomerase enzyme in urine by telomerase PCR and complete urine examination. Results : The results of this study revealed that a highly significant increase in the frequency of cytolological positive cases for tumor cells in malignant group than each of benign group and healthy subjects, while no significant difference was detected between benign group and healthy subjects. The frequency of telomerase in urine was significantly higher in malignant group than each of benign group and healthy subjects, while no significant difference was detected between benign group and healthy subjects. The telomerase activity has sensitivity of 90.6% for diagnosis of cancer bladder with 93.7% for specificity and PPV was 96.6%, NPV was 83.3% and

  9. 78 FR 11895 - Prospective Grant of Exclusive License: Development of MUC-1 Tumor Associated Antigens as Cancer...

    Science.gov (United States)

    2013-02-20

    ... Rights for development of Pox-virus based vaccines for bladder cancer, breast cancer, colorectal cancer... HUMAN SERVICES National Institutes of Health Prospective Grant of Exclusive License: Development of MUC-1 Tumor Associated Antigens as Cancer Vaccines for Bladder Cancer, Breast Cancer, Colorectal...

  10. Identification of Differently Expressed Genes in Chemical Carcinogen-induced Rat Bladder Cancers

    Institute of Scientific and Technical Information of China (English)

    Guangfu CHEN; Franky L. CHAN; Xu ZHANG; Peter S.F. CHAN

    2009-01-01

    Possible altered gene expression patterns in bladder turnout carcinogenesis in rat bladder cancers induced by BBN [N-butyl-N-(4-hydroxybutyl)nitrosamine] was examined by cDNA microarray analysis of gene expression profiles.Thirty Sprague-Dawley rats were given drinking water containing 0.05% BBN ad libitum for 24 to 28-weeks.Equal numbers of control rats were given tap water without BBN.After treatment,the rat bladders were excised for RNA extraction and histopathological examinations.Total RNAs were extracted from rat transitional cell carcinoma (TCC) tissues and micro-dissected normal rat bladder epithelia.The atlas glass rat microarray was used,which included oligonucleotides of 1081 rat genes.Some of the up-regulated genes in rat bladder TCCs were further confirmed by Northern blotting.Our results showed that the transcriptions of 30 genes were significantly elevated in the rat bladder TCCs,and these included fly proto-oncogene,Lipocortin 2,COX Ⅳ,COX Ⅴ a,and cathepsin D.Also,15 genes were significantly down-regulated in the rat bladder TCCs and they included B7.1,TNFrl,APOAI and VHL.The resuits of cDNA microarray analysis demonstrated that normal rat bladder epithelia and bladder TCC exhibited different and specific gene statement profiles.The increased expressions of the identified genes may play an important role in the chemically induced bladder carcinogenesis.

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

    Science.gov (United States)

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

    2015-09-01

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

  12. Early effects of preoperative radiation therapy for invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Isaka, Shigeo; Igarashi, Tatsuo; Ito, Haruo

    1983-10-01

    22 patients with high grade invasive bladder cancer were treated with preoperative radiation therapy (910 rad by fast neutron or 3000 rad by X ray during 2 weeks) followed by radical cystectomy and urinary diversion. 62.5 % of patients showed reduction in tumor size more than 50% evaluated by cystogram. Stage down was observed in 38% of patients compared between clinical and pathological stage. Histopathological effect of GII or GIII, according to the criteria described by Ohboshi, was noticed in 79 % of the patients. Better effect seemed to be obtained in fast neutron treated group than in X ray group. 19 patients received curative surgery, and 18 patients were alive without recurrence after 10 months (mean observed term). One died from lung metastasis 4.5 months after surgery. 50% of the patients complained of side effects of irradiation although they were tolerable, and 32% of the patients had major complications of surgery.

  13. Risk of bladder cancer in patients with diabetes

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Science.gov (United States)

    Lee, Esther J; Marcy, Todd R

    2014-08-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

  16. Effect of Allicin in Antagonizing Mice's Bladder Cancer in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    王坚; 何惠娟; 何承伟; 吴平; 柳建军

    2004-01-01

    Objective: To explore anti-tumor effect and mechanism of Allicin in treating murine bladder tumor. Methods: To observe Allicin's effect on MBT-2 tumor cells in vitro, 100 μg/ml Allicin was added to the tumor cell culture, and the morphology of tumor cells was observed by phase contrast microscope 6 hrs later.The direct effects of Allicin on tumor cell growth in vitro in the MTT Assay was also evaluated. To determine anti-tumor effect of Allicin in vivo, C3H/He mice were randomly grouped prior to initiation of experiment. The mice received 1 × 105 MBT-2 cells administered subcutaneously into the right posterior flank on the Day 0 the experiment started. Allicin was injected at the site near tumor transplantation on the Day 1. The mice were examined for tumor development and the tumors were measured in two dimensions with calipers twice a week. On Day 21 the tumors were resected and examined pathologically to see the immune response. Results: The observation of morphology of MBT-2 cells in vitro and MTT assay indicated that Allicin has apparent direct cytotoxicity to bladder cancer cells. In high dosage group, a marked delay was shown in the appearance and growth of tumors after subcutaneously injection when compared with the control group (P<0.01). Histology studies suggested that there were more macrophages, lymphocytes and fibroblasts at the peri-tumor region than the control group. Conclusion: Allicin has a marked tumor inhibitory effect on bladder tumor. This effect could possibly be related to direct cytotoxicity and activation of immune response. It could as possibly prove to be an effective intravesical treatment agent for superficial bladder cancer.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-11-01

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

  18. Attenuated XPC expression is not associated with impaired DNA repair in bladder cancer.

    Directory of Open Access Journals (Sweden)

    Kishan A T Naipal

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

  19. Bladder Stones

    Science.gov (United States)

    ... does not include routine preventive screening for bladder cancer.If you do not treat bladder stones, you can have lasting damage. This includes repeat UTIs or injury to your bladder, kidney, or urethra. Questions to ask your doctor How do I ...

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

    Science.gov (United States)

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

    1990-08-01

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

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

    Science.gov (United States)

    Ryder, R E J

    2015-03-01

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

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

    Science.gov (United States)

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

    2008-01-01

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

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

    Science.gov (United States)

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

  4. Parthenolide Induces Apoptosis and Cell Cycle Arrest of Human 5637 Bladder Cancer Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Guang Cheng

    2011-08-01

    Full Text Available Parthenolide, the principal component of sesquiterpene lactones present in medical plants such as feverfew (Tanacetum parthenium, has been reported to have anti-tumor activity. In this study, we evaluated the therapeutic potential of parthenolide against bladder cancer and its mechanism of action. Treatment of bladder cancer cells with parthenolide resulted in a significant decrease in cell viability. Parthenolide induced apoptosis through the modulation of Bcl-2 family proteins and poly (ADP-ribose polymerase degradation. Treatment with parthenolide led to G1 phase cell cycle arrest in 5637 cells by modulation of cyclin D1 and phosphorylated cyclin-dependent kinase 2. Parthenolide also inhibited the invasive ability of bladder cancer cells. These findings suggest that parthenolide could be a novel therapeutic agent for treatment of bladder cancer.

  5. Cases of a Borderline Pathology That Can Mimic Bladder Cancer: Primary Amyloidosis of Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Cemal Selçuk İşoğlu

    2015-06-01

    Full Text Available Amyloidosis is a disease characterised by accumulation of a fibrillar protein called amyloid in the extracellular space. The kidneys, ureters and the bladder can be affected in the urinary tract. However, primary amyloidosis of bladder is a rare entity. Macroscopic hematuria could be the first and only symptom of primary amyloidosis of the bladder; therefore, it has similar findings with urinary tract malignancies. Histopathological evaluation is mandatory for the diagnosis. Follow-up should always include cystoscopic evaluation as recurrence is expected in the natural course.

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

    Science.gov (United States)

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

    2016-04-01

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

  7. Anterior urethra sparing cystoprostatectomy for bladder cancer: a 10-year, single center experience

    OpenAIRE

    Hayakawa, Nozomi; Kikuno, Nobuyuki; Ishihara, Hiroki; Ryoji, Osamu; Tanabe, Kazunari

    2015-01-01

    Purpose Decision making regarding the urethra before and after radical cystectomy due to urothelial carcinoma has always been controversial. To determine whether anterior urethra sparing cystoprostatectomy for bladder cancer is an oncologically-safe procedure, we evaluated the long-term oncologic clinical outcome. Patients and methods A total of 51 male patients with cTa-4N0-2M0 bladder cancer were treated with anterior urethra sparing cystoprostatectomy and simultaneous urinary diversion bet...

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

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jiajia [Department of Laboratory Medicine, Peking University Third Hospital, Beijing (China); Zhu, Xi [Department of Urology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing (China); Zhang, Jie, E-mail: zhangjiebjmu@163.com [Department of Laboratory Medicine, Peking University Third Hospital, Beijing (China)

    2014-03-28

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

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

    Directory of Open Access Journals (Sweden)

    Acosta Giselle

    2007-03-01

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

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

    OpenAIRE

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

    2014-01-01

    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 mu m, 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 166 nm-sized lipid particles. The BCG-CWS encapsulated nano parti...

  11. The Investigation Image-guided Radiation Therapy of Bladder Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Seong Soo; Bae, Sun Myung; Kim, Jin San; Kang, Tae Young; Back, Geum Mun; Kwon, Kyung Tae [Dept. of Radiation Oncology, Asan Medical Center, Seoul (Korea, Republic of)

    2012-03-15

    In hospital image-guided radiation therapy in patients with bladder cancer to enhance the reproducibility of the appropriate amount, depending on the patient's condition, and image-guided injection of saline system (On-Board Imager system, OBI, VARIAN, USA) three of the Cone-Beam CT dimensional matching (3D-3D matching) to be the treatment. In this study, the treatment of patients with bladder cancer at Cone-Beam CT image obtained through the analysis of the bones based matching and matching based on the bladder to learn about the differences, the bladder's volume change injected saline solution by looking at the bladder for the treatment of patients with a more appropriate image matching is to assess how the discussion. At our hospital from January 2009 to April 2010 admitted for radiation therapy patients, 7 patients with bladder cancer using a Folly catheter of residual urine in the bladder after removing the amount determined according to individual patient enough to inject saline CT-Sim was designed after the treatment plan. After that, using OBI before treatment to confirm position with Cone-Beam CT scan was physician in charge of matching was performed in all patients. CBCT images using a total of 45 bones, bladder, based on image matching and image matching based on the difference were analyzed. In addition, changes in bladder volume of Eclipse (version 8.0, VARIAN, USA) persuaded through. Bones, one based image matching based on the bladder and re-matching the X axis is the difference between the average 3{+-}2 mm, Y axis, 1.8{+-}1.3 mm, Z-axis travel distance is 2.3{+-}1.7 mm and the overall 4.8{+-}2.0 mm, respectively. The volume of the bladder compared to the baseline showed a difference of 4.03{+-}3.97%. Anatomical location and nature of the bladder due to internal movement of the bones, even after matching with the image of the bladder occurred in different locations. In addition, the volume of saline-filled bladder showed up the difference

  12. DDX39 acts as a suppressor of invasion for bladder cancer.

    Science.gov (United States)

    Kato, Minoru; Wei, Min; Yamano, Shotaro; Kakehashi, Anna; Tamada, Satoshi; Nakatani, Tatsuya; Wanibuchi, Hideki

    2012-07-01

    The object of the present study was to identify markers for predicting urinary bladder cancer progression by comparative proteome analysis of bladder cancers and paired normal mucosas. We found that DDX39 was overexpressed in four of six bladder cancers examined compared with respective control tissues. Immunohistochemical analysis using 303 bladder cancer specimens revealed that DDX39 was inversely correlated to pT stage and histological grade progression. The incidence of DDX39(high) tumors (positive cells ≥50%) was 68.6%, 43.5%, 20.0%, and 5.3% in pTa, pT1, pTis, and ≥pT2 tumors, respectively, and 65.2%, 60.7%, and 19.6% in G1, G2, and G3 tumors, respectively. The incidence of DDX39(high) tumors was significantly lower in pT1 and ≥pT2 compared to pTa tumors, and also significantly lower in G3 compared to G1 and G2 tumors. Follow-up analysis (n = 105) revealed that DDX39(low) tumors (positive cells <50%) were associated with disease progression (hazard ratio 7.485; P = 0.0083). Furthermore, DDX39-knockdown bladder cancer cells increased their invasion ability compared to negative control cells. These results suggest that DDX39 is a suppressor of invasion and loss of its function predicts disease progression in bladder cancers.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2011-07-01

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

  15. Emerging concepts on drug resistance in bladder cancer: Implications for future strategies.

    Science.gov (United States)

    Massari, Francesco; Santoni, Matteo; Ciccarese, Chiara; Brunelli, Matteo; Conti, Alessandro; Santini, Daniele; Montironi, Rodolfo; Cascinu, Stefano; Tortora, Giampaolo

    2015-10-01

    The combination chemotherapies with methotrexate plus vinblastine, doxorubicin and cisplatin (MVAC or CMV regimens) or gemcitabine plus cisplatin represent the standard as first-line therapy for patients with metastatic urothelial cancer. In Europe, vinflunine is an option for second-line therapy for patients progressed during first-line or perioperative platinum-containing regimen. Alternative regimens containing taxanes and/or gemcitabine may be valuated case by case. Furthermore, carboplatin should be considered in patients unfit for cisplatin both in the first and second-line setting. Based on these findings, a better comprehension of the mechanisms underlying the development of drug resistance in patients with bladder cancer will represent a major step forward in optimizing patients' outcome. This article reviews the current knowledge of the mechanisms and emerging strategies to overcome resistance in patients with advanced urothelial cancer.

  16. The Role of Structural Extracellular Matrix Proteins in Urothelial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Andrea Brunner

    2007-01-01

    Full Text Available The extracellular matrix (ECM plays a key role in the modulation of cancer cell invasion. In urothelial carcinoma of the bladder (UC the role of ECM proteins has been widely studied. The mechanisms, which are involved in the development of invasion, progression and generalization, are complex, depending on the interaction of ECM proteins with each other as well as with cancer cells. The following review will focus on the pathogenetic role and prognostic value of structural proteins, such as laminins, collagens, fi bronectin (FN, tenascin (Tn-C and thrombospondin 1 (TSP1 in UC. In addition, the role of integrins mediating the interaction of ECM molecules and cancer cells will be addressed, since integrin-mediated FN, Tn-C and TSP1 interactions seem to play an important role during tumor cell invasion and angiogenesis.

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

    Science.gov (United States)

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

    2014-11-01

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

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

    Science.gov (United States)

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

    2014-10-15

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  1. Expression and significance of B7-H1 in peripheral blood dendritic cells from patients with bladder cancer

    Institute of Scientific and Technical Information of China (English)

    Chuanbiao Ji; Yonghua Wang; Qinchao Yu; Jing Liu; Yanan Liu; Jie Cui

    2013-01-01

    Objective: The aim of this study was to study the expression and the clinical significance of B7-H1 on dendritic cells (DCs) in peripheral blood from patients with bladder cancer. Methods: Peripheral blood mononuclear cell were disparted from 30 bladder cancer patients and 7 healthy controls by density gradient centrifugation and then co-cultured. The expression of B7-H1 on DCs were analyzed by flow cytometry. Results: Expression of B7-H1 on DCs in bladder cancer was higher than healthy controls (P < 0.01). And the expression were strongly associated with the pathological grade and clinical stage of bladder cancer (P < 0.05). Conclusion: The up-regulation of B7-H1 on DCs was strongly associated with neoplastic progression of bladder cancer. B7-H1/programmed death (PD)-1 signal pathway may also play an important role in immune escape of bladder cancer during initial phase of T cell immune response.

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

    Directory of Open Access Journals (Sweden)

    Sisi Wang

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

  3. [Transurethral en bloc resection of non-muscle invasive bladder cancer. What is the state of the art?].

    Science.gov (United States)

    Kramer, M W; Wolters, M; Abdelkawi, I F; Merseburger, A S; Nagele, U; Gross, A; Bach, T; Kuczyk, M A; Herrmann, T R W

    2012-06-01

    Bladder cancer of the urothelium is the second most common malignancy among urological tumors. In view of a worldwide aging population and the fact that increased incidence rates are associated with higher age, new socioeconomic challenges will appear. Even nowadays the treatment of bladder cancer bears the highest lifetime treatment costs per patient among all forms of cancer. In conjunction with higher comorbidity rates among older patients urologists are facing new challenges in the treatment and care of patients with bladder cancer. The standard treatment for non-muscle invasive bladder cancer (NMIBC) is monopolar transurethral resection using resection loops (TURB). Based on experience in the surgical treatment of benign prostatic hyperplasia, different concepts of en bloc resection of bladder tumors using alternative energy resources (e.g. holmium laser, thulium laser and the water-jet HybridKnife) have been developed. Goals of new treatment modalities are reduction of perioperative and postoperative comorbidities, better pathological work-up of the specimens and increased recurrence-free survival. Postulated advantages using laser devices are a more precise cutting line as well as better hemostasis. The evidential value of this review is limited due to the lack of randomized, prospective studies. However, there is a tendency towards a limitation of perioperative and postoperative morbidities as well as higher chance of well-preserved tissues for better pathohistological evaluation using en bloc resection methods. More studies with long-term follow-up periods and better randomization are needed to clarify whether en bloc strategies provide better long-term oncological survival.

  4. Optical spectroscopy by 5-aminolevulinic acid hexylester induced photodynamic treatment in rat bladder cancer

    Science.gov (United States)

    Larsen, Eivind L. P.; Randeberg, Lise L.; Gederaas, Odrun A.; Arum, Carl-Jørgen; Krokan, Hans E.; Hjelme, Dag R.; Svaasand, Lars O.

    2006-02-01

    Photodynamic therapy (PDT) is a treatment modality which has been shown to be effective for both malignant and non-malignant diseases. New photosensitizers such as 5-aminolevulinic acid hexylester (hALA) may increase the efficiency of PDT. Monitoring of the tissue response provides important information for optimizing factors such as drug and light dose for this treatment modality. Optical spectroscopy may be suited for this task. To test the efficacy of hALA induced PDT, a study on rats with a superficial bladder cancer model, in which a bladder cancer cell line (AY-27) is instilled, will be performed. Preliminary studies have included a PDT feasibility study on rats, fluorescence spectroscopy on AY-27 cell suspensions, and optical reflection and fluorescence spectroscopy in rat bladders in vivo. The results from the preliminary studies are promising, and the study on hALA induced PDT treatment of bladder cancer will be continued.

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

    Institute of Scientific and Technical Information of China (English)

    Wei-Xing Shi; Shu-Qing Chen

    2004-01-01

    AIM: To investigate the association between cytochrome P450 2C19 (CYP2C19) gene polymorphism and cancer susceptibility by genotyping of CYP2C19 poor metabolizers (PMs) in cancer patients.METHODS: One hundred and thirty-five cases of esophagus cancer, 148 cases of stomach cancer, 212 cases of lung cancer, 112 cases of bladder cancer and 372 controls were genotyped by allele specific amplification-polymerase chain reaction (ASA-PCR) for CYP2C19 PMs. The frequencies of PMs in cancer groups and control group were compared.RESULTS: The frequencies of PMs of CYP2C19 were 34.1%(46/135) in the group of esophagus cancer patients, 31.8%(47/148) in the stomach cancer patients, 34.4%(73/212) in the group of lung cancer patients, only 4.5% (5/112) in the bladder cancer patients and 14.0%(52/372) in control group.There were statistical differences between the cancer groups and control group (esophagus cancer, x2=25.65, P<0.005,OR=3.18, 95% CI=2.005-5.042; stomach cancer, x2=21.70,P<0.005, OR=2.86, 95%CI=1.820-4.501; lung cancer,x2=33.58, P<0.005, OR=3.23, 95%CI=1.503-6.906; bladder cancer, x2=7.50, P<0.01, OR=0.288, 95%CI=0.112-0.740).CONCLUSION: CYP2C19 PMs have a high incidence of esophagus cancer, stomach cancer and lung cancer, conversely they have a low incidence of bladder cancer. It suggests that CYP2C19 may participate in the activation of procarcinogen of esophagus cancer, stomach cancer and lung cancer, but may involve in the detoxification of carcinogens of bladder cancer.

  6. Molecular Biomarkers in Bladder Cancer: Novel Potential Indicators of Prognosis and Treatment Outcomes

    Directory of Open Access Journals (Sweden)

    Masayoshi Nagata

    2016-01-01

    Full Text Available Although many clinical and molecular markers for predicting outcomes in bladder cancer (BC have been reported, their application in clinical practice remains unclear. Bladder carcinogenesis has two distinct molecular pathways that direct the development of BC. FGFR3 mutations are common in low-grade BC, while TP53 mutation or loss of RB1 is associated with muscle-invasive BC. However, no tissue-based gene markers confirmed by prospective large-scale trials in BC have been used in clinical practice. Micro-RNA analyses of BC tissue revealed that miR-145 and miR-29c⁎ function as tumor suppressors, whereas miR-183 and miR-17-5p function as oncogenic miRNAs. In liquid biopsy, circulating tumor cells (CTC, exosomes, or cell-free RNA is extracted from the peripheral blood samples of cancer patients to analyze cancer prognosis. It was reported that detection of CTC was associated with poor prognostic factors. However, application of liquid biopsy in BC treatment is yet to be explored. Although several cell-free RNAs, such as miR-497 in plasma or miR-214 in urine, could be promising novel circulating biomarkers, they are used only for diagnosing BC as the case that now stands. Here, we discuss the application of novel biomarkers in evaluating and measuring BC outcomes.

  7. Radical irradiation and misonidazole for T2 grade III and T3 bladder cancer: 2 year follow-up

    Energy Technology Data Exchange (ETDEWEB)

    Abratt, R.P.; Barnes, D.R.; Hammond, J.A.; Sarembok, L.A.; Tucker, R.D.; Williams, A.M.

    1984-09-01

    Patients with T2 grade III and T3 bladder cancer were treated in a Phase II trial of radical irradiation plus Misonidazole (MISO). Twenty-two patients were treated and the results compared with historical controls. The cystoscopic complete tumor response between 6 and 12 months post therapy were 73 and 43%, respectively. The patient two year survival was 81 and 51%, respectively, and the patient 2 year survival with bladder preservation was 61 and 48%, respectively - 4 patients in the MISO study having undergone salvage cystectomy. Complications that may be radiation related in the MISO study are would sepsis after salvage cystectomy in 2 patients, rectal stenosis requiriing colostomy 16 months after salvage cystecomy in 1 patient and the development of a contracted bladder in 1 patient with a history of prior extensive endoscopic therapy. No misonidazole neurotoxicity seen. These findings are being further evaluated in a prospective radomized trial.

  8. Welfare Assessment following Heterotopic or Orthotopic Inoculation of Bladder Cancer in C57BL/6 Mice.

    Science.gov (United States)

    Miller, Amy; Burson, Hannah; Söling, Ariane; Roughan, Johnny

    2016-01-01

    Few studies have assessed whether mice used as cancer models experience pain. Despite this possibility, the usual practice is to withhold analgesics as these are generally viewed as confounding. However, pain also alters cancer progression, so preventing it might not only be beneficial to welfare but also to study validity. Establishing the extent to which different cancer models result in pain is an important first step towards their refinement. We used conditioned place preference (CPP) testing and body-weight and behaviour analyses to evaluate the assumption that heterotopically implanted tumours result in less pain and fewer welfare concerns than those implanted orthotopically. C57Bl/6 mice received MB49Luc luciferase expressing bladder cancer cells or saline implanted subcutaneously or into the bladder. These tumour-bearing or control groups underwent 2 daily 45 minute conditioning trials to saline or morphine (2mg/kg) and then a 15 minute drug-free preference test on day 3 of a 3 day cycle, continuing until the study ended. Tumours were imaged and behaviour data obtained following preference tests. Development of preference for the morphine-paired chamber (morphine-seeking) was determined over time. Heterotopic tumour development had no effect on morphine-seeking, and although the restraint used for heterotopic inoculation caused greater initial weight losses than anaesthesia, these mice steadily gained weight and behaved comparatively normally throughout the study. Orthotopic tumour inoculation caused no initial weight losses, but over the final 7 days these mice became less active and lost more body weight than cancer-free controls. This indicated orthotopic implantation probably caused a more negative impact on welfare or conceivably pain; but only according to the current test methods. Pain could not be confirmed because morphine-seeking in the tumour-bearing groups was similar to that seen in controls. Imaging was not found to be an effective method of

  9. Welfare Assessment following Heterotopic or Orthotopic Inoculation of Bladder Cancer in C57BL/6 Mice.

    Directory of Open Access Journals (Sweden)

    Amy Miller

    Full Text Available Few studies have assessed whether mice used as cancer models experience pain. Despite this possibility, the usual practice is to withhold analgesics as these are generally viewed as confounding. However, pain also alters cancer progression, so preventing it might not only be beneficial to welfare but also to study validity. Establishing the extent to which different cancer models result in pain is an important first step towards their refinement. We used conditioned place preference (CPP testing and body-weight and behaviour analyses to evaluate the assumption that heterotopically implanted tumours result in less pain and fewer welfare concerns than those implanted orthotopically. C57Bl/6 mice received MB49Luc luciferase expressing bladder cancer cells or saline implanted subcutaneously or into the bladder. These tumour-bearing or control groups underwent 2 daily 45 minute conditioning trials to saline or morphine (2mg/kg and then a 15 minute drug-free preference test on day 3 of a 3 day cycle, continuing until the study ended. Tumours were imaged and behaviour data obtained following preference tests. Development of preference for the morphine-paired chamber (morphine-seeking was determined over time. Heterotopic tumour development had no effect on morphine-seeking, and although the restraint used for heterotopic inoculation caused greater initial weight losses than anaesthesia, these mice steadily gained weight and behaved comparatively normally throughout the study. Orthotopic tumour inoculation caused no initial weight losses, but over the final 7 days these mice became less active and lost more body weight than cancer-free controls. This indicated orthotopic implantation probably caused a more negative impact on welfare or conceivably pain; but only according to the current test methods. Pain could not be confirmed because morphine-seeking in the tumour-bearing groups was similar to that seen in controls. Imaging was not found to be an

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

    Science.gov (United States)

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

    2014-01-01

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

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

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    Shanshan Wang

    Full Text Available 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

  12. [Neoadjuvant chemotherapy of invasive cancer of the urinary bladder].

    Science.gov (United States)

    Selivanov, S P; Isaeva, S N; Kovalik, T A; Chén', M N; Aleksandrovich, I N; Kaliev, E A

    2007-01-01

    We studied efficacy of a combination of intraosseous and systemic administration of drugs in patients with invasive cancer of the urinary bladder (UB). A total of 20 patients aged 54-79 years with verified had recurrence, 2 had tumors with continuous growth. T2N0M0 UB carcinoma was diagnosed in 7 patients, T3N0M0--in 12, T6N0M0--in 1 patient. All the patients received systemic chemotherapy with gemzar in a single daily dose 800-1000 mg/m2 on day 1, 7 and 14. On day 2 a single intraosseous 100 mg eloxatin was given. A total of three courses of combined chemotherapy with 4-week interval was used. Intravenous gemzar administration was accompanied with mild leukopenia in 4 patients, moderate leukopenia--in 1, allergic reaction--in 2 patients. This required gemzar discontinuation. No side effects were seen in response to intraosseous administration of eloxatin. The combined chemotherapy produced complete regression of UB cancer in 3 of 18 patients, partial regression--in 12, stabilization--in 3 patients. Neither local nor long-term tumor progression was found. Short-term therapeutic efficacy of combined therapy was 70%. Fifteen patients with partial regression or stabilization have undergone transurethral resection. Duration of a recurrence-free period reached 5 to 72 months (mean 17 months). The neoadjuvant chemotherapy proposed by us allows achievement of a high percentage of regression in patients with invasive UB cancer located in UB cervix and provides concervative surgery including patients over 70 years of age.

  13. High risk bladder cancer: current management and survival

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    Anna M. Leliveld

    2011-04-01

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

  14. Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival

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    Hsieh Fu-Chuan

    2008-10-01

    Full Text Available Abstract Background Constitutive activation of signal transducer and activator of transcription 3 (Stat3 signaling pathway plays an important role in several human cancers. Activation of Stat3 is dependent on the phosphorylation at the tyrosine residue 705 by upstream kinases and subsequent nuclear translocation after dimerization. It remains unclear whether oncogenic Stat3 signaling pathway is involved in the oncogenesis of bladder cancer. Results We found that elevated Stat3 phosphorylation in 19 of 100 (19% bladder cancer tissues as well as bladder cancer cell lines, WH, UMUC-3 and 253J. To explore whether Stat3 activation is associated with cell growth and survival of bladder cancer, we targeted the Stat3 signaling pathway in bladder cancer cells using an adenovirus-mediated dominant-negative Stat3 (Y705F and a small molecule compound, STA-21. Both prohibited cell growth and induction of apoptosis in these bladder cancer cell lines but not in normal bladder smooth muscle cell (BdSMC. The survival inhibition might be mediated through apoptotic caspase 3, 8 and 9 pathways. Moreover, down-regulation of anti-apoptotic genes (Bcl-2, Bcl-xL and survivin and a cell cycle regulating gene (cyclin D1 was associated with the cell growth inhibition and apoptosis. Conclusion These results indicated that activation of Stat3 is crucial for bladder cancer cell growth and survival. Therefore, interference of Stat3 signaling pathway emerges as a potential therapeutic approach for bladder cancer.

  15. Cisplatin resistance by induction of aldo-keto reductase family 1 member C2 in human bladder cancer cells

    OpenAIRE

    Shirato, Akitomi; KIKUGAWA, TADAHIKO; Miura, Noriyoshi; Tanji, Nozomu; Takemori, Nobuaki; Higashiyama, Shigeki; Yokoyama, Masayoshi

    2013-01-01

    Cisplatin is currently the most effective anti-tumor agent available against bladder cancer. To clarify the mechanism underlying cisplatin resistance in bladder cancer, the present study examined the role of the aldo-keto reductase family 1 member C2 (AKR1C2) protein on chemoresistance using a human bladder cancer cell line. The function of AKR1C2 in chemoresistance was studied using the human HT1376 bladder cancer cell line and the cisplatin-resistant HT1376-CisR subline. AKR1C2 was expresse...

  16. A study of an effective sunitinib–chemotherapeutic combination regimen for bladder cancer treatment using a mouse model

    Directory of Open Access Journals (Sweden)

    Dah-Shyong Yu

    2014-06-01

    Conclusion: Combination of the tyrosine kinase receptor inhibitor sunitinib with gemcitabine chemotherapy synergistically enhances tumor cytotoxicity and may provide a new treatment modality for advanced bladder cancer.

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

    Science.gov (United States)

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

    2006-01-01

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

  18. Distinct pattern of p53 mutations in bladder cancer

    DEFF Research Database (Denmark)

    Spruck, C H; Rideout, W M; Olumi, A F

    1993-01-01

    A distinct mutational spectrum for the p53 tumor suppressor gene in bladder carcinomas was established in patients with known exposures to cigarette smoke. Single-strand conformational polymorphism analysis of exons 5 through 8 of the p53 gene showed inactivating mutations in 16 of 40 (40%) bladder...

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

    Science.gov (United States)

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

    2015-04-01

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

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

    Science.gov (United States)

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

    2012-05-01

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

  1. Emerging intravesical therapies for management of nonmuscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Jeffrey J Tomaszewski

    2010-05-01

    Full Text Available Jeffrey J Tomaszewski, Marc C SmaldoneDepartment of Urology, University of Pittsburgh School of Medicine, Pennsylvania, USAAbstract: Transitional cell carcinoma (TCC is the second most common urologic malignancy, and 70% of patients present with superficial or nonmuscle invasive bladder cancer (NMIBC. Intravesical bacillus Calmette-Guerin (BCG is the most effective agent for preventing disease recurrence, and the only therapy able to inhibit disease progression. However, recurrence rates as high as 30% and significant local and systemic toxicity have led to increased interest in alternative intravesical therapies. In patients refractory or intolerant to BCG, BCG-interferon α2b, gemcitabine, and anthracyclines (doxorubicin, epirubicin, valrubicin have demonstrated durable clinical responses. Phase I trials investigating alternative cytotoxic agents, such as apaziquone, taxanes (docetaxel, paclitaxel, and suramin are reporting promising data. Novel immunomodulating agents have demonstrated promise as efficacious alternatives in patients refractory to BCG. Optimization of existing chemotherapeutic regimens using hyperthermia, photodynamic therapy, magnetically-targeted carriers, and liposomes remains an area of active investigation. Despite enthusiasm for new intravesical agents, radical cystectomy remains the treatment of choice for patients with NMIBC who have failed intravesical therapy and selected patients with naïve T1 tumors and aggressive features. This report provides a comprehensive review of contemporary intravesical therapy for NMIBC and refractory NMIBC, with an emphasis on emerging agents and novel treatment modalities.Keywords: transitional cell carcinoma, nonmuscle, invasive, intravesical therapy, BCG

  2. MOLECULAR GENETIC MARKERS AS PREDICTORS OF SUPERFICIAL BLADDER CANCER

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    A. Yu. Babayan

    2009-01-01

    Full Text Available A system of clinical and morphological criteria is currently used to determine the pattern of superficial bladder cancer (SBC. However, this system does not completely reflect the clinical potential of SBC and needs additional markers. The purpose of this study was to search for and evaluate molecular genetic disorders as additional markers of the course of SBC. The diagnostic panel included the deletion of the loci 3р14, 9р21, 9q34, 17р13 (ТР53, mutations of exon 7 of the FGFR3 gene, and hypermethylation of the promoter regions of the RASSF1, RARB, p16, p14, CDH1 genes. The study was made on 108 matched samples (tumor/peripheral blood obtained from patients with SBC. The deletions of the loci 3р14, 9р21 and anomalous methylation of the RARb and p16 genes are markers of the worse course of SBC while FGFR3 gene mutation is a marker of better prognosis. In the context of estimation of the relapsing potential of a primary tumor, the 9p21 locus deletion is a marker associated with recurrence within the first year after malignancy resection. The group of molecular genetic markers determined by the authors for poor prognosis in combination with classical clinical and morphological criteria will specify the pattern of the course of the disease and its prognosis.

  3. Assessment criteria for compensation of occupational bladder cancer.

    Science.gov (United States)

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

    2013-01-01

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

  4. GENETIC RISK MARKERS FOR SUPERFICIAL AND INVASIVE BLADDER CANCER

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    V. N. Pavlov

    2011-01-01

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

  5. Metabolism and growth inhibitory activity of cranberry derived flavonoids in bladder cancer cells.

    Science.gov (United States)

    Prasain, Jeevan K; Rajbhandari, Rajani; Keeton, Adam B; Piazza, Gary A; Barnes, Stephen

    2016-09-14

    In the present study, anti-proliferative activities of cranberry derived flavonoids and some of their in vivo metabolites were evaluated using a panel of human bladder tumor cell lines (RT4, SCABER, and SW-780) and non-tumorigenic immortalized human uroepithelial cells (SV-HUC). Among the compounds tested, quercetin 3-O-glucoside, isorhamnetin (3'-O-methylquercetin), myricetin and quercetin showed strong concentration-dependent cell growth inhibitory activities in bladder cancer cells with IC50 values in a range of 8-92 μM. Furthermore, isorhamnetin and myricetin had very low inhibitory activity against SV-HUC even at very high concentrations (>200 μM) compared to bladder cancer cells, indicating that their cytotoxicity is selective for cancer cells. To determine whether the differential cell growth inhibitory effects of isomeric flavonoids quercetin 3-O-glucoside (active) and hyperoside (quercetin 3-O-galactoside) (inactive) are related to their metabolism by the cancer cells, SW-780 cells were incubated with these compounds and their metabolism was examined by LC-MS/MS. Compared to quercetin 3-O-glucoside, hyperoside undergoes relatively less metabolic biotransformation (methylation, glucuronidation and quinone formation). These data suggest that isorhamnetin and quercetin 3-O-glucoside may be the active forms of quercetin in prevention of bladder cancer in vivo and emphasize the importance of metabolism for the prevention of bladder cancer by diets rich in cranberries.

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

    Science.gov (United States)

    Mao, Song; Huang, Songming

    2013-06-01

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

  7. Radiation treatment planning for bladder cancer: a comparison of cystogram localisation with computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Rothwell, R.I.; Ash, D.V.; Jones, W.G. (Cookridge Hospital, Leeds (UK))

    1983-01-01

    A comparison has been made between the target volumes of radical radiotherapy treatment plans produced with the aid of marker cystograms, and target volumes derived from computed tomography (CT) scans in 60 patients with bladder cancer. This has demonstrated inadequacies of the cystograms due to the inability to delineate extravesical spread of tumour and, as many patients with bladder cancer had a significant residual urine, emptying the bladder by catheterisation may have given a false impression of the shape and size of the target volume. Analysis of the results showed that cystographic localisation resulted in serious underdosage of the tumour in 18% of patients and failure to include all the bladder in 37%. Conventionally produced target volumes showed potentially significant discrepancies in 85% of patients when compared with target volumes delineated by CT.

  8. Effect of oral administration of Shiquandabu pill combined with bladder perfusion chemotherapy on the postoperative recurrence and malignant degree of superficial bladder cancer

    Institute of Scientific and Technical Information of China (English)

    Qiang Zhang; Yi-Shi Xing; Meng-Jia Cui; Zeng-Yue Yang

    2016-01-01

    Objective:To study the effect of oral administration of Shiquandabu pill combined with bladder perfusion chemotherapy on the postoperative recurrence and malignant degree of superficial bladder cancer.Methods:A total of 102 patients with superficial bladder cancer who received transurethral resection of bladder tumor in our hospital between April 2012 and April 2015 were selected and randomly divided into combined group who received postoperative oral administration of Shiquandabu pill combined with bladder perfusion chemotherapy and routine group who received postoperative bladder perfusion chemotherapy, the postoperative tumor recurrence was followed up for 3 years, and the levels of tumor markers in serum as well as the expression levels of stem cell marker molecules and immunoregulation molecules in peripheral blood and recurrent lesions were determined.Results: Postoperative 1-year recurrence rate and postoperative 3-year recurrence rate of combined treatment group were significantly lower than those of routine group, and the mean recurrence time was significantly longer than that of routine group; 1 year after operation, serum VEGF, αFGF,βFGF, MMP2 and MMP9 levels were significantly lower than those of routine group, and ALDH1, Sox2, Nanog, CD47, CD133, B7-H1, PD-1 and PD-L1 mRNA levels in peripheral blood mononuclear cells were significantly lower than those of routine group; after tumor recurrence, ALDH1, Sox2, Nanog, CD47, CD133, B7-H1, PD-1 and PD-L1 mRNA levels in recurrent lesions of combined treatment group were significantly lower than those of routine group.Conclusion:Oral administration of Shiquandabu pill combined with bladder perfusion chemotherapy has better effect on preventing postoperative recurrence of superficial bladder cancer than bladder perfusion chemotherapy alone, and it has regulating effect on tumor load, characteristics of stem cells and immune response after transurethral resection of bladder tumor.

  9. Intra-fractional bladder motion and margins in adaptive radiotherapy for urinary bladder cancer

    DEFF Research Database (Denmark)

    Grønborg, Caroline; Vestergaard, Anne; Høyer, Morten

    2015-01-01

    BACKGROUND: The bladder is a tumour site well suited for adaptive radiotherapy (ART) due to large inter-fractional changes, but it also displays considerable intra-fractional motion. The aim of this study was to assess target coverage with a clinically applied method for plan selection ART and to...

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

    Science.gov (United States)

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

    2017-01-01

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

  11. Urine Telomerase: An Important Marker in the Diagnosis of Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Maria Aurora Sanchini

    2004-05-01

    Full Text Available Telomerase activity is present in most human malignant tumors, whereas it is generally not detectable, with some exceptions, in normal cells. Therefore, it represents a potential tool for tumor detection. In the present study, telomerase activity was determined in urine from 79 healthy individuals and 121 previously untreated bladder cancer patients using a highly sensitive telomeric repeat amplification protocol (TRAP assay and the results were expressed as arbitrary enzymatic units (AEU. This approach enabled us to identify cutoff values characterized by high sensitivity (from 75% to 93% and specificity (from 72% to 92%. Moreover, analysis as a function of gender showed a higher accuracy of TRAP assay in males (93% sensitivity and 90% specificity at the cutoff of 50 AEU than in females. This sensitivity was confirmed in patients with nonassessable or negative cytology. In women, morphological and immunocytochemical determinations using a human telomerase reverse transcriptase monoclonal antibody (anti-hTERT recently developed in our laboratory showed a large fraction of immunoreactive inflammatory or nonbladder cells, which may justify the false-positive TRAP results. In conclusion, this assay represents an important noninvasive diagnostic tool to detect bladder cancer also in patients with negative or nonassessable urine cytology and with low-grade and early-stage lesions.

  12. Small cell cancer of the bladder: The Leon-Berard cancer centre experience

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    Nabil Ismaili

    2008-01-01

    Full Text Available Background: Small cell bladder carcinoma is an uncommon tumor. In this retrospective study we report our experience dealing with this disease at the Leon-Berard Cancer Centre. Materials and Methods: We retrospectively analyzed various characteristics of small cell bladder carcinoma: patient demographics, histological diagnosis, disease stage, treatment effects and outcome, in 14 non-metastatic small cell bladder carcinoma patients treated at our institution between 1995 and 2006. Results: The mean age at diagnosis was 60 years (range, 45-77. All patients were male. Seventy-five per cent were smokers. All had locally advanced disease. Ten patients (71.4% were treated by cystoprostatectomy and bilateral pelvic lymph node resection, one by cystoprostatectomy alone. Two patients received neoadjuvant chemotherapy and four received adjuvant chemotherapy. One patient was treated by radiotherapy with concomitant cisplatin after transurethral resection of bladder tumor (TURBT. One patient refused surgery and was treated by chemotherapy alone. One patient was lost to follow-up after TURBT. After 49-month median follow-up, 12 patients had relapsed. Disease-free survival was 5.7 months. The most frequent sites of relapse were the retroperitoneal lymph node (seven patients and the liver (three patients. Nine patients died of metastasis. Median overall survival was 29.5 months. Survival probability at two years was 58%. Median overall survival was 34 months in the mixed small carcinoma group, as compared with 9.5 months in the pure small cell carcinoma group (P=0.01. Mean overall survival was 27.2 months for all patients and 38.6 months for patients treated with cystectomy and adjuvant chemotherapy. Conclusion: To date, the optimal treatment for locally advanced small cell bladder carcinoma is not clear. Cystectomy with neoadjuvant or adjuvant chemotherapy appears as a viable option.

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

    Science.gov (United States)

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

    2015-09-01

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

  14. Acceleration of Apoptosis by Transfection of Bak Gene in Multi-drug Resistant Bladder Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    LIUYing; ZENGFuqing

    2004-01-01

    To study the killing effects of bak gene on multi-drug resistant (MDR) bladder cancer cells and the mechanisms. Methods: Bak gene was transfected into MDR bladder cancer cells by liposome. The expression of bak and Bcl-2 mRNA was detected by in situ hybridization. The expression of bak and Bcl-2 proteins was detected by SABC immunohistochemistry. The growth rate of human bladder cancer cells was studied by constructing the growth curve, cell apoptosis was measured by flow cytometry, and the morphology of cells was observed by fluorescence stain. Results: The expression of bak mRNA was positive in EJ/bak cells (P<0.05). Bak protein expression of EJ/bak cells was positive and Bcl-2 protein expression was decreased (P<0.05). The growth of MDR bladder cancer cells was significantly inhibited after bak gene was transfected (P<0.05). Apoptosis cells were increased significantly. The apoptosis rate was 35%. Apoptotic bodies can be found in these cells by fluorescence stain. Conclusion: Bak gene could inhibit the growth of MDR bladder cancer cells effectively. Inducing cell apoptosis by down-regulating the expression of Bcl-2 gene might be one of its mechanisms.

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

    Science.gov (United States)

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

    1984-05-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2002-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jorge R. Ramos

    2014-04-01

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

  19. Polymorphisms in the XRCC1 gene modify survival of bladder cancer patients treated with chemotherapy

    NARCIS (Netherlands)

    Sacerdote, C.; Guarrera, S.; Ricceri, F.; Pardini, B.; Polidoro, S.; Allione, A.; Critelli, R.; Russo, A.; Andrew, A.S.; Ye, Y.; Wu, X.; Kiemeney, L.A.L.M.; Bosio, A.; Casetta, G.; Cucchiarale, G.; Destefanis, P.; Gontero, P.; Rolle, L.; Zitella, A.; Fontana, D.; Vineis, P.; Matullo, G.

    2013-01-01

    Survival of bladder cancer patients depends on several factors including disease stage and grade at diagnosis, age, health status of the patient and the applied treatment. Several studies investigated the role of DNA repair genetic variants in cancer susceptibility, but only few studies investigated

  20. Treatment and outcome in muscle invasive bladder cancer : a population-based survey

    NARCIS (Netherlands)

    Leliveld, Anna M.; Doornweerd, Benjamin H. J.; Bastiaannet, Esther; Schaapveld, Michael; de Jong, Igle J.

    2010-01-01

    OBJECTIVE: To assess treatments and survival of patients with muscle invasive bladder cancer (MIBC) in the Comprehensive Cancer Center Northern Netherlands (CCCN) region. STUDY DESIGN AND SETTING: Retrospective cohort analysis. Data of 548 patients with MIBC diagnosed between 1997 and 2002 were coll

  1. [Development of bladder stone following a tension-free vaginal tape procedure: a case report].

    Science.gov (United States)

    Tolosa Eizaguirre, Egoitz; Rincón Mayans, Aníbal; Zuazu, Jorge Rioja; Bergera, Juan J Zudaire; Abad, Javier Barba; Polo, José Ma Berián

    2009-06-01

    The bladder stone formation due to intravesical mesh erosion of tension-free vaginal tape (TVT) is an infrequent complication. We report a case of 73 years old woman, treated in two occasions by means of the positioning of a TVT with the intention of treating its urinary incontinence. The symptoms, of a year of evolution, was characterized by disuria, pelvic pain, diarrea and constitutional syndrome. RM showed bladder stone fixed to bladder wall. The extraction of the bladder stone was made by the section of the polypropilene mesh on which the calculi had been developed. 6 months later, control cystoscopy revealed complete healing of bladder mucosa.

  2. CREATION OF THE NOMOGRAM THAT PREDICTS PATHOLOGICAL LOCAL EXTENT OF THE BLADDER CANCER BASED ON CLINICAL VARIABLES

    Directory of Open Access Journals (Sweden)

    L. V. Mirylenka

    2014-08-01

    Full Text Available Objective: to develop nomogram based on clinical variables, that predicts pathological local extent of the bladder cancer рТ3-рТ4 (рТ3+.Material and methods: We used data of 511 patients with bladder cancer, that have undergone radical cystectomy between 1999 and 2008 at N.N. Alexandrov National Cancer Centre. For prediction of pT3+ on preoperative data were used mono- and multivariate logistic regression analysis. Coefficients from logistic regression equalization were used to construct nomogram. Nomogram accuracy was evaluated with concordance index (с-index and by building the calibration plot. Internal validation by bootstrap method with 200 variants of dataset was performed.Results: We developed nomogram, that include: clinical stage сТ, tumor grade, tumor macroscopic appearance, presence of upper tract dilatation, prostatic urethra and/or prostatic lobe(s involvement, 3 or more bladder walls involvement, ESR and creatinine level. Bootstrapcorrected prognostic accuracy of nomogram was 81,4%, that 12,6% better than clinical stage accuracy.Conclusion: developed nomogram can significantly improve pathologic tumor stage prediction accuracy that may be used to select patients for neoadjuvant chemotherapy.

  3. CREATION OF THE NOMOGRAM THAT PREDICTS PATHOLOGICAL LOCAL EXTENT OF THE BLADDER CANCER BASED ON CLINICAL VARIABLES

    Directory of Open Access Journals (Sweden)

    L. V. Mirylenka

    2012-01-01

    Full Text Available Objective: to develop nomogram based on clinical variables, that predicts pathological local extent of the bladder cancer рТ3-рТ4 (рТ3+.Material and methods: We used data of 511 patients with bladder cancer, that have undergone radical cystectomy between 1999 and 2008 at N.N. Alexandrov National Cancer Centre. For prediction of pT3+ on preoperative data were used mono- and multivariate logistic regression analysis. Coefficients from logistic regression equalization were used to construct nomogram. Nomogram accuracy was evaluated with concordance index (с-index and by building the calibration plot. Internal validation by bootstrap method with 200 variants of dataset was performed.Results: We developed nomogram, that include: clinical stage сТ, tumor grade, tumor macroscopic appearance, presence of upper tract dilatation, prostatic urethra and/or prostatic lobe(s involvement, 3 or more bladder walls involvement, ESR and creatinine level. Bootstrapcorrected prognostic accuracy of nomogram was 81,4%, that 12,6% better than clinical stage accuracy.Conclusion: developed nomogram can significantly improve pathologic tumor stage prediction accuracy that may be used to select patients for neoadjuvant chemotherapy.

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

    Institute of Scientific and Technical Information of China (English)

    Zhi-qiang WANG; Jun ZHAO; Jin ZENG; Kai-jie WU; Yu-le CHEN; Xin-ya ng WANG; Luke S CHANG; Da-lin HE

    2011-01-01

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

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

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    Sunil Gupta

    2015-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  9. Trends in cancer of the urinary bladder and urinary tract in elderly in Denmark, 2008-2012

    DEFF Research Database (Denmark)

    Jensen, Thor Knak; Jensen, Niels Viggo; Jørgensen, Simon Møller

    2016-01-01

    Background The aim of this study was to examine the trends in incidence, mortality, survival, and prevalence of cancers of the urinary bladder and urinary tract in Denmark from 1980 to 2012 with particular focus on elderly patients over age 70 years. Design Cancer of the urinary bladder and urinary...

  10. Autophagy inhibition sensitizes bladder cancer cells to the photodynamic effects of the novel photosensitizer chlorophyllin e4.

    Science.gov (United States)

    Du, Lihuan; Jiang, Ning; Wang, Guozeng; Chu, Yiwei; Lin, Wei; Qian, Jing; Zhang, Yuanfang; Zheng, Jingcun; Chen, Gang

    2014-04-05

    We previously developed a novel photosensitizer, chlorophyllin e4, and found that chlorophyllin e4 mediated-PDT could kill 5637 and T24 cells by inducing apoptotic cell death. Here, we further investigated the new mechanism of autophagy and determined its relevance to apoptosis in e4-PDT. We demonstrated that chlorophyllin e4 was located in both lysosome and mitochondria, and autophagy also occurred in bladder cancer cells upon e4-PDT. More importantly, autophagy played a pro-survival role, and its inhibition enhanced e4-PDT-associated apoptotic cell death because cells pretreated with the typical autophagy inhibitor either 3-methyladenine or Bafilomycin A1 exhibited much lower cell viability and higher apoptotic cell death. Thus, these data imply that the combination of PDT, when mediated by our new photosensitizer chlorophyllin e4, and an autophagy inhibitor might be a promising approach to the eliminationof non-muscle invasive bladder cancer.

  11. Planned preoperative cisplatin and radiation therapy for locally advanced bladder cancer.

    Science.gov (United States)

    Herr, H W; Yagoda, A; Batata, M; Sogani, P C; Whitmore, W F

    1983-12-15

    Cisplatin (DDP) is an active agent in the treatment of disseminated bladder cancer. In addition to its direct tumor cytotoxicity, recent animal and clinical data suggest synergism with radiation therapy (RT). Since improved survival with preoperative RT is largely restricted to bladder cancer patients in whom radiation-induced downstaging (P less than T) may be recognized, the authors administered DDP + RT preoperatively to patients with locally advanced (T3, T4) bladder tumors selected for cystectomy. The aim was to evaluate the feasibility of such a combination in relation to surgical and hematologic complications, the immediate effect on tumor downstaging, disease progression, and survival. Two thousand rad (400 rad X 5 days) was delivered to the whole pelvis, followed by cystectomy in 2 days. DDP (70 mg/m2) was given intravenously on day 2 of the RT. Twenty-four patients received preoperative DDP + RT and underwent attempted cystectomy; however, six patients were nonresectable owing to extensive pelvic disease, and an additional five patients had resectable pelvic lymph node metastases. Pelvic complications developed in 3 of 24 (12%) patients, but none required reoperation. No patient had a wound dehiscence. Transient myelosuppression was similar to that induced by 2000 rad preoperative RT alone. Tumor downstaging (P less than T) was seen in 9 of 24 (38%) patients, and in 5 (21%) patients, no tumor was found in the surgical specimen (P0). Distant metastases alone have been detected in 4 of 18 (22%) patients who had a cystectomy (all 4 had nodal metastases). Disease-free survival at a median follow-up of 22 months (range, 12-34 months) is 60% (14/24) for all patients (89% for P less than T and 40% for P greater than or equal to T patients) and 78% (14/18) for the resected patients. Combined preoperative DDP + RT proved to be a safe and feasible regimen which resulted in a possibly greater recognition of radioresponsive bladder tumors, and after cystectomy, an

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-03-01

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

  14. THE RECURRENCE AFTER ORGAN-SAVING SURGERY OF PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    T. A. Sveklina

    2014-08-01

    Full Text Available The article represents the study of frequency and nature of the recurrence and survival rate (common, oncology-specific, disease-free after organ-saving surgery of patients with muscle-invasive bladder cancer stages T2b and T3a. Oncology-speсific and disease-free survival rates were much higher if full diagnosis of bladder mucosa, the adjuvant intravesical chemotherapy had been on pre-operative and intra-operative stages than in the absence of these diagnosis and therapy. Recurrentes of bladder cancer which appeared in the absence of diagnosis and combination therapy, statistically reliably occured at another location other than the zone of operation, stage of recurrentes and degree of differentiation of recurrents were less than the original tumor. This information confirms the existence of foci of cancer in situ which have not been identified on the diagnostic stage.

  15. In Vitro and In Vivo Experiments on Electrochemotherapy for Bladder Cancer

    DEFF Research Database (Denmark)

    Vásquez, Juan Luis; Ibsen, Per; Lindberg, Henriette;

    2015-01-01

    PURPOSE: Electrochemotherapy is widely performed to treat solid tumors but experience with bladder cancer is limited. We investigated mitomycin C and cisplatin administered with electrochemotherapy for bladder cancer in vitro and in vivo. MATERIALS AND METHODS: The human bladder cancer cell line SW......780 was used. Cells were treated with electroporation, drug alone or electroporation plus increasing concentrations of drug (mitomycin C 0.001 to 2,000 μM or cisplatin 1.56 to 300 μM). Electrochemotherapy parameters were 8 pulses of 1.2 kV/cm for 99 microseconds at 1 Hz. We investigated survival...... and apoptosis, the latter evaluated by caspase activity. NMRI-Fox1nu nude mice were inoculated subcutaneously and randomized to 1) electrochemotherapy plus NaCl, 2) NaCl alone, 3) electrochemotherapy plus drug or 4) drug alone (mitomycin C 5 mM or cisplatin 250 μM). Tumors were measured 3 times per week...

  16. Evidence-based clinical practice guidelines for bladder cancer (summary - JUA 2009 Edition).

    Science.gov (United States)

    2010-02-01

    In Japan, until now, the treatment of bladder cancer has been based on guidelines from overseas. The problem with this practice is that the options recommended in overseas guidelines are not necessarily suitable for Japanese clinical practice. A relatively large number of clinical trials have been conducted in Japan in the field of bladder cancer, and the Japanese Urological Association (JUA) considered it appropriate to formulate their own guidelines. These Guidelines present an overview of bladder cancer at each clinical stage, followed by clinical questions that address problems frequently faced in everyday clinical practice. In this English translation of a shortened version of the original Guidelines, we have abridged each overview, summarized each clinical question and its answer, and only included the references we considered of particular importance.

  17. Stage-associated overexpression of the ubiquitin-like protein, ISG15, in bladder cancer

    DEFF Research Database (Denmark)

    Andersen, JB; Jensen, Mads Aaboe; Borden, EC;

    2006-01-01

    at different stages of progression. The innate immune response gene, interferon-stimulated gene 15 kDa (ISG15, GIP2), was highly expressed at all stages of bladder cancer as compared to normal urothelium. Western blotting revealed a tumour-associated expression of ISG15 protein. ISG15 exhibited a stage...... expression of ISG15 protein in both cancer cells and stromal immune cells. Interestingly, a significant fraction of ISG15 protein was localised to the nuclei of tumour cells, whereas no nuclear ISG15 staining was observed in ISG15-positive stromal cells. Taken together, our findings identify ISG15 as a novel......Bladder cancer is among the most prevalent malignancies, and is characterised by frequent tumour recurrences and localised inflammation, which may promote tissue invasion and metastasis. Microarray analysis was used to compare gene expression in normal bladder urothelium with that in tumours...

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

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

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

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

    Science.gov (United States)

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

    2014-10-01

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

  20. A 3-plex methylation assay combined with the FGFR3 mutation assay sensitively detects recurrent bladder cancer in voided urine

    DEFF Research Database (Denmark)

    Kandimalla, Raju; Masius, Roy; Beukers, Willemien;

    2013-01-01

    Purpose: DNA methylation is associated with bladder cancer and these modifications could serve as useful biomarkers. FGFR3 mutations are present in 60% to 70% of non–muscle invasive bladder cancer (NMIBC). Low-grade bladder cancer recurs in more than 50% of patients. The aim of this study......, and nonmalignant urines (n = 130). Results: The 3-plex assay identified recurrent bladder cancer in voided urine with a sensitivity of 74% in the validation set. In combination with the FGFR3 mutation assay, a sensitivity of 79% was reached (specificity of 77%). Sensitivity of FGFR3 and cytology was 52% and 57......%, respectively. Conclusion: The combination of methylation and FGFR3 assays efficiently detects recurrent bladder cancer without the need for stratification of patients regarding methylation/mutation status of the primary tumor. We conclude that the sensitivity of this combination is in the same range...

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

    Science.gov (United States)

    Davidson, Mayer B

    2016-08-01

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

  2. Transfection of promyelocytic leukemia in retrovirus vector inhibits growth of human bladder cancer cells

    Institute of Scientific and Technical Information of China (English)

    Lei LI; Da-lin HE

    2005-01-01

    Aim: To construct a recombinant retrovirus vector carrying human promyelocytic leukemia (PML) cDNA and identify its expression and biology role in bladder cancer UM-UC-2 cells for future gene therapy. Methods: PML full-length cDNA was inserted into the EcoR I and BamHI site of pLXSN vector containing the long terminal repeat (LTR) promoter. The vector was identified by restriction enzyme digestion and then transfected into PA317 packaging cell line by calcium phosphate coprecipitation. PML cDNA was detected by polymerase chain reaction (PCR) and the protein was identified by laser confocal microscopy and Western blot in bladder cancer cells, respectively. The morphology was observed by inverted phase contrast microscope, and MTT assay determined growth curve of the bladder cancer cells. Results: Restriction enzyme digestion proved that a 2.1kb PML cDNA was inserted into the pLXSN vector. PCR assay demonstrated that 304 bp fragments were found in UM-UC-2/pLPMLSN transfects. Laser confocal microscopy showed speck dots fluorescence in the UM-UC-2/pLPMLSN nucleus.A 90 kD specific brand was found by Western blot. MTT assay demonstrated the UM-UC-2/pLPMLSN bladder cancer growth inhibition. Conclusion: The retrovirus pLPMLSN vector was successfully constructed and could generate high effective expression of human PML in bladder cancer cell UM-UC-2, suggesting that PML recombinant retrovirus have potential utility in the gene therapy for bladder cancer.

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

    Science.gov (United States)

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

    2014-01-01

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

  4. Inhibiting cell migration and cell invasion by silencing the transcription factor ETS-1 in human bladder cancer.

    Science.gov (United States)

    Liu, Li; Liu, Yuchen; Zhang, Xintao; Chen, Mingwei; Wu, Hanwei; Lin, Muqi; Zhan, Yonghao; Zhuang, Chengle; Lin, Junhao; Li, Jianfa; Xu, Wen; Fu, Xing; Zhang, Qiaoxia; Sun, Xiaojuan; Zhao, Guoping; Huang, Weiren

    2016-05-03

    As one of the members of the ETS gene family, the transcription factor v-ets avian erythroblastosis virus E26 oncogene homolog 1 (ETS-1) plays key role in the regulation of physiological processes in normal cells and tumors. In this study, we aimed to investigate the relationship between the transcription factor ETS-1 and malignant phenotypes of bladder cancer. We demonstrated that ETS-1 was up-regulated in human bladder cancer tissue compared to paired normal bladder tissue. In order to evaluate the functional role of ETS-1 in human bladder cancer, vectors expressing ETS-1 shRNA and ETS-1 protein were constructed in vitro and transfected into the human bladder cancer T24 and 5637 cells. Our results showed that the transcription factor ETS-1 could promote cell migration and cell invasion in human bladder cancer, without affecting cell proliferation and apoptosis. In conclusion, ETS-1 plays oncogenic roles through inducing cell migration and invasion in human bladder cancer, and it can be used as a therapeutic target for treating human bladder cancer.

  5. Sentinel lymph node biopsy in bladder cancer: Systematic review and technology update

    OpenAIRE

    Liss, Michael A.; Noguchi, Jonathan; Lee, Hak J.; Vera, David R.; Kader, A. Karim

    2015-01-01

    A sentinel lymph node (SLN) is the first lymph node to drain a solid tumor and likely the first place metastasis will travel. SLN biopsy has been well established as a staging tool for melanoma and breast cancer to guide lymph node dissection (LND); its utility in bladder cancer is debated. We performed a systematic search of PubMed for both human and animal studies that looked at SLN detection in cases of urothelial carcinoma of the bladder. We identified a total of nine studies that assesse...

  6. The utility of tumour markers in assessing the response to chemotherapy in advanced bladder cancer

    OpenAIRE

    Cook, A M; Huddart, R A; Jay, G; Norman, A.; Dearnaley, D. P.; Horwich, A

    2000-01-01

    In patients with advanced bladder cancer receiving chemotherapy, early assessment of response can avoid unnecessary toxicity. The aim of this study was to assess the role of tumour markers in monitoring response. Serum levels of one or more of markers β human chorionic gonadotrophin (βhCG), carcinoembryomic antigen (CEA), CA125 and CA19.9 were measured in 74 patients with advanced bladder cancer receiving chemotherapy from 1992 to 1997. Forty-three of 74 (58%) of patients had at least one rai...

  7. A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: The future is now.

    Science.gov (United States)

    Bellmunt, Joaquin; Powles, Thomas; Vogelzang, Nicholas J

    2017-03-01

    The treatment of bladder cancer has evolved over time to encompass not only the traditional modalities of chemotherapy and surgery, but has been particularly impacted by the use of immunotherapy. The first immunotherapy was the live, attenuated bacterial Bacillus Calmette-Guérin vaccine, which has been the standard of care non-muscle-invasive bladder cancer since 1990. Modern immunotherapy has focused on inhibitors of checkpoint proteins, which are molecules that impede immune function, thereby allowing tumor cells to grow and proliferate unregulated. Several checkpoint targets (programmed death ligand-1 [PD-L1] programmed cell death protien-1 [PD-1], and cytotoxic T-lymphocyte associated protein 4 [CTLA4]) have received the most attention in the treatment of bladder cancer, and have inhibitor agents either approved or in late-stage development. This review describes the most recent data on agents that inhibit PD-L1, found on the surface of tumor cells, and PD-1 found on activated T and B cells and macrophages. Atezolizumab is the only member of this class currently approved for the treatment of bladder cancer, but nivolumab, pembrolizumab, durvalumab, and avelumab all have positive results for this indication, and approvals are anticipated in the near future. The checkpoint inhibitors offer an effective alternative for patients for whom previously there were few options for durable responses, including those who are ineligible for cisplatin-based regimens or who are at risk of significant toxicity. Research is ongoing to further categorize responses, define ideal patient populations, and investigate combinations of checkpoint inhibitors to address multiple pathways in immune system functioning.

  8. Proteomic analysis of urinary biomarker candidates for nonmuscle invasive bladder cancer.

    Science.gov (United States)

    Lindén, Mårten; Lind, Sara Bergström; Mayrhofer, Corina; Segersten, Ulrika; Wester, Kenneth; Lyutvinskiy, Yaroslav; Zubarev, Roman; Malmström, Per-Uno; Pettersson, Ulf

    2012-01-01

    Nonmuscle invasive tumors of the bladder often recur and thereby bladder cancer patients need regular re-examinations which are invasive, unpleasant, and expensive. A noninvasive and less expensive method, e.g. a urine dipstick test, for monitoring recurrence would thus be advantageous. In this study, the complementary techniques mass spectrometry (MS) and Western blotting (WB)/dot blot (DB) were used to screen the urine samples from bladder cancer patients. High resolving MS was used to analyze and quantify the urinary proteome and 29 proteins had a significantly higher abundance (pblot for four selected proteins; fibrinogen β chain precursor, apolipoprotein E, α-1-antitrypsin, and leucine-rich α-2-glycoprotein 1. Dot blot analysis of an independent urine sample set pointed out fibrinogen β chain and α-1-antitrypsin as most interesting biomarkers having sensitivity and specificity values in the range of 66-85%. Exploring the Human Protein Atlas (HPA) also revealed that bladder cancer tumors are the likely source of these proteins. They have the potential of being useful in diagnosis, monitoring of recurrence and thus may improve the treatment of bladder tumors, especially nonmuscle invasive tumors.

  9. A RETROSPECTIVE STUDY OF THE EFFICACY OF CHEMOIRRADIATION IN LOCALLY ADVANCED URINARY BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    Nehru

    2015-04-01

    Full Text Available BACKGROUND : Radical cystectomy with pelvic lymph node dissection is the standard method used to treat patients with locally advanced carcinoma of urinary bladder. Furthermore, a significant proportion of patients are deemed unsuitable for surgery due to inoperability, advanced age, and/or comorbid conditions. B ecause of disappointing results with radical cystectomy in terms of survival, as well as the morbidity and decreased quality of life associated with the surgery, bladder - conserving therapies like trimodality (TURBT, concurrent chemoradiation therapy have been gained popularity as the survival rates are nearly equal with radical cystectomy along with functioning bladder. AIM OF STUDY : To study retrospectively the effectiveness of chemoradition therapy in bladder preservation approach in the management of p atients with locally advanced ( I nvasive bladder cancer in medically unfit and unwilling patients for radical cystectomy and those who cannot tolerate combination chemotherapy drugs. METHOD S AND MATERIAL : The data was collected from the patient’s records between 2004 - 2010 who were treated in our Regional cancer hospital. All were biopsy/CT scan proven muscle invasive urinary bladder tumors with T2 – 3, N0, M0 lesions. Post TURBT status. Medi cally unfit and Unwillingness for surgery and underwent concurrent Radiotherapy with weekly cisplatin therapy. And men and / women with age between 45 - 70 years were included in the study. RESULTS : Out of 28 patients 4 (14.29% patients who had good TURP procedure showed complete response , 20(71.43% patients had partial response and 4(14.29% patients showed stable disease. 71.43% patient showed symptomatic response to treatment . CONCLUSION : Being a single agent chemotherapy with radiation and it is feasible without major toxicity and offers a potentially usefulness in locoregional control and symptomatic relief in unfavorable population with invasive bladder cancer. Moreover it

  10. Bladder cancer: utility of MRI in detection of occult muscle-invasive disease

    Energy Technology Data Exchange (ETDEWEB)

    Rosenkrantz, Andrew B. [Dept. of Radiology, NYU Langone Medical Center, New York (United States)], E-mail: Andrew.rosenkrantz@nyumc.org; Mussi, Thais C. [Dept. of Radiology, NYU Langone Medical Center, New York (United States); Hospital Israelita Albert Einstein, Sao Paulo (Brazil); Melamed, Jonathan [Dept. of Pathology, NYU Langone Medical Center, New York (United States); Taneja, Samir S.; Huang, William C. [Dept. of Urology, Div. of Urologic Oncology, NYU Langone Medical Center, New York (United States)

    2012-07-15

    Background. The presence of muscularis propria invasion by bladder cancer is a key factor in prognosis and treatment decisions, although may be missed by biopsy due to sampling error. MRI has shown potential for detection of muscle invasion but has not specifically been evaluated for this purpose in the setting of bladder cancer patients without evidence of muscle invasion on initial biopsy. Purpose. To evaluate the role of MRI in detection of muscularis propria invasion by bladder cancer following a pathologic diagnosis of non-invasive tumor. Material and Methods. This retrospective study included 23 patients who underwent pelvic MRI following a pathologic diagnosis of bladder cancer without muscularis propria invasion and in whom additional histologic evaluation was performed following MRI. Two radiologists in consensus reviewed T2-weighted images to identify those cases suspicious for muscle invasion on MRI. The radiologists identified whether cases suspicious for invasion demonstrated disruption of the T2-hypointense muscularis layer of the bladder wall, peri-vesical fat stranding, and peri-vesical soft tissue nodularity. Findings were compared with pathologic results obtained after MRI. Results. Suspicion was raised for muscle invasion in eight of 23 cases, four of which exhibited invasion on follow-up pathology. No case without suspicion on MRI exhibited invasion on follow-up pathology. Therefore, sensitivity and specificity were 100% and 79%, respectively. Among individual findings, muscularis disruption on T2WI exhibited sensitivity of 100% and specificity of 79%, peri-vesical fat stranding exhibited sensitivity and specificity of 50% and 84%, and peri-vesical soft tissue nodularity exhibited sensitivity and specificity of 25% and 100%. Conclusion. MRI demonstrated high sensitivity for detection of muscle invasion in cases of bladder cancer without invasion on initial histologic assessment. Muscularis disruption on T2WI appeared to exhibit a better

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

    Science.gov (United States)

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

    2010-01-01

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

  12. Analysis of the Sonic Hedgehog signaling pathway in normal and abnormal bladder development.

    Science.gov (United States)

    DeSouza, Kristin R; Saha, Monalee; Carpenter, Ashley R; Scott, Melissa; McHugh, Kirk M

    2013-01-01

    In this study, we examined the expression of Sonic Hedgehog, Patched, Gli1, Gli2, Gli3 and Myocardin in the developing bladders of male and female normal and megabladder (mgb-/-) mutant mice at embryonic days 12 through 16 by in situ hybridization. This analysis indicated that each member of the Sonic Hedgehog signaling pathway as well as Myocardin displayed distinct temporal and spatial patterns of expression during normal bladder development. In contrast, mgb-/- bladders showed both temporal and spatial changes in the expression of Patched, Gli1 and Gli3 as well as a complete lack of Myocardin expression. These changes occurred primarily in the outer mesenchyme of developing mgb-/- bladders consistent with the development of an amuscular bladder phenotype in these animals. These results provide the first comprehensive analysis of the Sonic Hedgehog signaling pathway during normal bladder development and provide strong evidence that this key signaling cascade is critical in establishing radial patterning in the developing bladder. In addition, the lack of detrusor smooth muscle development observed in mgb-/- mice is associated with bladder-specific temporospatial changes in Sonic Hedgehog signaling coupled with a lack of Myocardin expression that appears to result in altered patterning of the outer mesenchyme and poor initiation and differentiation of smooth muscle cells within this region of the developing bladder.

  13. Clinical impact of bladder biopsies with TUR-BT according to cytology results in patients with bladder cancer: a case control study

    Directory of Open Access Journals (Sweden)

    Matsumoto Kazuhiro

    2010-06-01

    Full Text Available Abstract Background There seems to be no consensus concerning taking bladder biopsies during transurethral resection of bladder tumor (TUR-BT. We investigate the clinical significance of bladder biopsy with TUR-BT and the relationship between urinary cytology and the biopsy results. Methods We reviewed a total of 424 patients with non-muscle invasive bladder cancer treated with TUR-BT between 1998 and 2005. Of the total, 293 patients also underwent a bladder biopsy. Biopsies from suspicious-appearing urothelium (N = 59 and those from normal-appearing urothelium (N = 234 were evaluated separately. Results Bladder cancer was observed in 23 cases (39.0% who underwent a biopsy of suspicious-appearing urothelium. Among these 23 cases, 9 cases with visible tumor resection had carcinoma in situ (CIS only in the biopsies from suspicious-appearing urothelium. Urinary cytology was negative in 3 of the 9 cases. Bladder cancer was observed in 26 cases (11.1% who underwent a biopsy of normal-appearing urothelium. Of them, 5 cases with visible tumors had CIS only in the multiple biopsies from normal-appearing urothelium. Urinary cytology was positive in all of the 5 cases. No upstaging or upgrading cases were found in these patients by the addition of these two types of biopsy. Furthermore, therapy was not altered in these patients. With or without bladder biopsy was not a significant factor for tumor recurrence in either the univariate or multivariate analysis. Conclusions Based on the results, it is concluded the multiple biopsies from normal-appearing urothelium are not necessary in patients with negative cytology results because of the low detection rate and lack of influence on therapeutic decisions. Meanwhile, biopsy of suspicious-appearing urothelium is needed in patients with negative cytology results in order to detect CIS due to staging properties. This result supports a recent EAU guideline.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

    Joshi, Ashish; Preslan, Elicia

    2011-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Angela A G van Tilborg

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

  17. Alternative splicing in colon, bladder, and prostate cancer identified by exon-array analysis

    DEFF Research Database (Denmark)

    Thorsen, Kasper; Sørensen, Karina D.; Brems-Eskildsen, Anne Sofie;

    2008-01-01

    Alternative splicing enhances proteome diversity and modulates cancer-associated proteins. To identify tissue- and tumor-specific alternative splicing, we used the GeneChip Human Exon 1.0 ST Array to measure whole-genome exon expression in 102 normal and cancer tissue samples of different stages......, and 18 candidate tumor-specific splicing alterations in colon, bladder, and prostate, respectively, were selected for RT-PCR validation on an independent set of 81 normal and tumor tissue samples. In total, seven genes with tumor-specific splice variants were identified (ACTN1, CALD1, COL6A3, LRRFIP2...... from colon, urinary bladder, and prostate. We identified 2069 candidate alternative splicing events between normal tissue samples from colon, bladder, and prostate and selected 15 splicing events for RT-PCR validation, 10 of which were successfully validated by RT-PCR and sequencing. Furthermore 23, 19...

  18. The Use of Regenerative Medicine in the Management of Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Matthew E. Hyndman

    2012-01-01

    Full Text Available Muscle invasive and recurrent nonmuscle invasive bladder cancers have been traditionally treated with a radical cystectomy and urinary diversion. The urinary diversion is generally accomplished through the creation of an incontinent ileal conduit, continent catheterizable reservoir, or orthotopic neobladder utilizing small or large intestine. While radical extirpation of the bladder is often successful from an oncological perspective, there is a significant morbidity associated with enteric interposition within the genitourinary tract. Therefore, there is a great opportunity to decrease the morbidity of the surgical management of bladder cancer through utilization of novel technologies for creating a urinary diversion without the use of intestine. Clinical trials using neourinary conduits (NUC seeded with autologous smooth muscle cells are currently in progress and may represent a significant surgical advance, potentially eliminating the complications associated with the use of gastrointestinal segments in the urinary reconstruction, simplifying the surgical procedure, and greatly facilitating recovery from cystectomy.

  19. Metastatic Bladder Cancer Presenting with Persistent Hematuria in Young Man with Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Premal Patel

    2013-01-01

    Full Text Available We report a case of metastatic bladder cancer developing in a young man with cystic fibrosis (CF that was initially diagnosed as ureterolithiasis and managed as renal colic. With the improved survival of patients with CF, an increasing burden of extrapulmonary disease manifestations is apparent. Renal colic is observed at an increased frequency in patients with CF relative to the general population and is a commonly recognized cause of hematuria. However, CF patients harboring a malignancy are recognized to be at increased risk of delayed identification owing to atypical symptoms and lack of demographic risk factors. This case illustrates how investigations to rule out malignancy are warranted in those CF patients not responding to therapies directed towards presumptive diagnoses.

  20. Metastatic bladder cancer presenting with persistent hematuria in young man with cystic fibrosis.

    Science.gov (United States)

    Patel, Premal; Rabin, Harvey R; Vickers, Michael M; Parkins, Michael D

    2013-01-01

    We report a case of metastatic bladder cancer developing in a young man with cystic fibrosis (CF) that was initially diagnosed as ureterolithiasis and managed as renal colic. With the improved survival of patients with CF, an increasing burden of extrapulmonary disease manifestations is apparent. Renal colic is observed at an increased frequency in patients with CF relative to the general population and is a commonly recognized cause of hematuria. However, CF patients harboring a malignancy are recognized to be at increased risk of delayed identification owing to atypical symptoms and lack of demographic risk factors. This case illustrates how investigations to rule out malignancy are warranted in those CF patients not responding to therapies directed towards presumptive diagnoses.

  1. Development of bladder control in mentally handicapped children

    Directory of Open Access Journals (Sweden)

    Bruschini Homero

    2003-01-01

    Full Text Available PURPOSE:To analyze the role of mental handicap as a possible source of lack of development of bladder control and to find out the chance of continence to advise future patients. MATERIALS AND METHODS: The parents and relatives of 100 consecutive mentally handicapped patients were inquired by a personal interview. Questions included the age when they stopped using diapers, enuretic events, frequency, urgency and leakage episodes, urinary infections. Etiology of their mental problem was unknown in 34, perinatal anoxia in 17, Down syndrome in 15, phenylketonuria in 18 and others minors causes. The grade of mental deficiency were profound in 1, severe in 10, moderate in 39, mild in 33 and normal inferior value in 17. The age varied from 7 to 37 years old, with an average of 14 by the time of the interview, comprising 60 males and 40 females. RESULTS: All profound and severe patients presented leakage episodes regardless of the age. The mild and normal inferior value acquired progressive urinary control with aging, and 33% still remain with urinary symptoms above 16 years old. Urinary infection was similar in males and females, around 29%. The most committed group presented less urinary infections. The etiology of the mental handicap was not correlated to the incidence of urinary leakage. CONCLUSIONS: The lack of bladder control was correlated to the grade of mental handicap. In severe and profound groups, the expectancy of control is disappointing. In the less compromised groups, there is a delay in bladder training, with achievement of control in 2/3 after 16 years of age. Those in the normal inferior value have a chance of postponed urinary control, easily misdiagnosed by normal urological interviews.

  2. Knockdown of Ki-67 by dicer-substrate small interfering RNA sensitizes bladder cancer cells to curcumin-induced tumor inhibition.

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    Sivakamasundari Pichu

    Full Text Available Transitional cell carcinoma (TCC of the urinary bladder is the most common cancer of the urinary tract. Most of the TCC cases are of the superficial type and are treated with transurethral resection (TUR. However, the recurrence rate is high and the current treatments have the drawback of inducing strong systemic toxicity or cause painful cystitis. Therefore, it would be of therapeutic value to develop novel concepts and identify novel drugs for the treatment of bladder cancer. Ki-67 is a large nucleolar phosphoprotein whose expression is tightly linked to cell proliferation, and curcumin, a phytochemical derived from the rhizome Curcuma longa, has been shown to possess powerful anticancer properties. In this study, we evaluated the combined efficacy of curcumin and a siRNA against Ki-67 mRNA (Ki-67-7 in rat (AY-27 and human (T-24 bladder cancer cells. The anticancer effects were assessed by the determination of cell viability, apoptosis and cell cycle analysis. Ki-67-7 (10 nM and curcumin (10 µM, when treated independently, were moderately effective. However, in their combined presence, proliferation of bladder cancer cells was profoundly (>85% inhibited; the rate of apoptosis in the combined presence of curcumin and Ki-67-7 (36% was greater than that due to Ki-67-7 (14% or curcumin (13% alone. A similar synergy between curcumin and Ki-67-7 in inducing cell cycle arrest was also observed. Western blot analysis suggested that pretreatment with Ki-67-7 sensitized bladder cancer cells to curcumin-mediated apoptosis and cell cycle arrest by p53- and p21-independent mechanisms. These data suggest that a combination of anti-Ki-67 siRNA and curcumin could be a viable treatment against the proliferation of bladder cancer cells.

  3. Tissue polypeptide antigen in the follow-up of patients with urinary bladder cancer compared with conventional urine cytology.

    Science.gov (United States)

    Bantis, Athanasios; Zissimopoulos, Athanasios; Sountoulides, Petros; Giannakopoulos, Stilianos; Kalaitzis, Christos; Athanassiadou, Paulina; Agelonidou, Eleni; Touloupidis, Stavros

    2010-01-01

    The incidence of bladder cancer has demonstrated a rapid increase during the last decades. The aim of this study is to determine the clinical value of serum tissue polypeptide antigen (TPA) as a tumour marker for urinary bladder cancer in comparison with conventional urine cytology. Urine and blood samples were obtained from a total of 108 patients (group A) with a known history of bladder cancer, who presented for their routine 3 month follow-up. These 108 patients included 45 patients with high grade and 63 patients with low grade bladder cancer, and 30 patients with lower urinary tract symptoms (LUTS) and no history of bladder cancer (group B). Urine and blood samples from fifty healthy adults (group C) were also tested; this group served as the control group for estimating the normal range of serum TPA values. In all group A patients cystoscopy and/or bladder biopsies were performed. All blood and urine samples were tested for TPA and conventional urine cytology respectively. Results showed that the upper normal range for TPA was 1.0 ng/mL(0.9 ± 0.04) in the control group. For the subgroups of patients with high and low grade bladder cancer elevated serum TPA levels were found in 52% and 40% of the patients respectively. The overall serum TPA sensitivity and specificity were 50% and 85% respectively for patients with known bladder cancer (group A). We found the sensitivity of cytology for high grade bladder (GIII) carcinomas to be 72%; however when urine cytology was combined with serum TPA the overall sensitivity reached 80%. We conclude that serum TPA combined with urine cytology may be used as a prognostic marker for bladder cancer.

  4. Polymorphism of Glutathione S-transferase T1, M1 and P1 Genes in a Shanghai Population: Patients With Occupational or Non-occupational Bladder Cancer

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective Glutathione S-transferases are involved in the conjugation of xenobiotics. To explore whether GSTs polymorphisms are involved in the development of occupational or non-occupational bladder cancer, polymorphism frequencies of GSTT1, M1 and P1 were investigated in a normal population, which had been settled in a rural area in Shanghai suburb for at least 5 generations as well as in a group of patients with benzidine exposure related occupational bladder cancer in Shanghai dyestuff industry and a group of patients with non-occupational bladder cancer. Methods PCR based procedures were performed in the study populations to confirm the genotypes of GSTT1, M1 and P1. Results The polymorphisms at locus of GSTP1- A1578G in the normal population differed significantly from those in Caucasians or African Americans. All the subjects genotyped so far (n =118) bore only homogenous wild genotype (C2293/ C2293) at GSTP1 - C2293T locus. This locus seemed to be a monomorphic in Shanghai population. No significant difference in GSTT1 and GSTM1 polymorphic form frequencies could be confirmed among three groups of subjects. An overrepresentation of GSTP1 AG or GG genotype corresponding a less stable and less effective isozyme protein was detected in patients with benzidine related occupational bladder cancer, compared with that in the normal population though a statistical significance was not yet reached (P=0.09, OR=1.96, 95% CI 0.89-4.32,). Conclusion This study suggests that GSTM1 or GSTT1 homozygous deficiency genotypes and their combination do not have a clear impact on bladder cancer incidence in a Shanghai population. It seems that GSTP1 polymorphism is not associated with non-occupational bladder cancer. GSTP1 AG or GG genotype has a higher frequency in the patients with benzidine related occupational bladder cancer, and further work is needed to confirm if GSTP1 AG or GG genotype plays a role in the development of occupational bladder cancer.

  5. Identification of pro-inflammatory cytokines associated with muscle invasive bladder cancer; the roles of IL-5, IL-20, and IL-28A.

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    Se-Jung Lee

    Full Text Available We used gene expression profiling to identify inflammatory cytokines that correlate with bladder cancer development. Gene expression profiles of the tissue samples were investigated using cDNA microarrays that contained 103 non-muscle invasive bladder cancers (NMIBC, 62 muscle invasive bladder cancers (MIBC, 58 samples of histologically normal-looking surrounding tissues, and 10 normal, healthy subjects who served as the control cohort for comparison. We grouped the data-sets according to biological characterizations and focused on immune response genes with at least 2-fold differential expression in MIBC vs. controls. The experimental data-set identified 36 immune-related genes that were significantly altered in MIBC samples. In addition, 10 genes were up-regulated and 26 genes were down-regulated in MIBC samples compared with the normal tissues. Among the 10 up-regulated molecules examined, the capacity for both wound-healing migration and invasion was enhanced in response to IL-5, IL-20, and IL-28A in bladder cancer cell lines (253J and EJ cells, compared with untreated cells. The expression levels of IL-5, IL-20, and IL-28A were increased in patients with MIBC. All 3 cytokines and their receptors were produced in bladder cancer cell lines, as determined by real-time PCR, immunoblot analysis and confocal immunofluorescence. Up-regulation of MMP-2 and MMP-9 was found after IL-5, IL-20, and IL-28A stimulation in both cell types. Moreover, an EMSA assay showed that treatment with IL-5, IL-20, and IL-28A induced activation of the transcription factors NF-κB and AP-1 that regulate the MMP-9 promoter. Finally, activation of MAPK and Jak-Stat signaling was observed after the addition of IL-5, IL-20, and IL-28A to bladder cancer cells. This study suggests the presence of specific inflammatory cytokine (IL-5, IL-20, and IL-28A-mediated association in bladder cancer development. All 3 cytokines may be important new molecular targets for the modulation

  6. Genetic variants in urinary bladder cancer: collective power of the "wimp SNPs".

    Science.gov (United States)

    Golka, Klaus; Selinski, Silvia; Lehmann, Marie-Louise; Blaszkewicz, Meinolf; Marchan, Rosemarie; Ickstadt, Katja; Schwender, Holger; Bolt, Hermann M; Hengstler, Jan G

    2011-06-01

    In recent years, genome-wide association studies (GWAS) have identified more than 300 validated associations between genetic variants and risk of approximately 70 common diseases. A small number of rare variants with a frequency of usually less than 1% are associated with a strongly enhanced risk, such as genetic variants of TP53, RB1, BRCA1, and BRCA2. Only a very small number of SNPs (with a frequency of more that 1% of the rare allele) have effects of a factor of two or higher. Examples include APOE4 in Alzheimer's disease, LOXL1 in exfoliative glaucoma, and CFH in age-related macular degeneration. However, the majority of all identified SNPs have odds ratios between 1.1 and 1.5. In the case of urinary bladder cancer, all known SNPs that have been validated in sufficiently large populations are associated with odds ratios smaller than 1.5. These SNPs are located next to the following genes: MYC, TP63, PSCA, the TERT-CLPTM1L locus, FGFR3, TACC3, NAT2, CBX6, APOBEC3A, CCNE1, and UGT1A. It is likely that these moderate risk or "wimp SNPs" interact, and because of their high number, collectively have a strong influence on whether an individual will develop cancer or not. It should be considered that variants identified so far explain only approximately 5-10% of the overall inherited risk. Possibly, the remaining variance is due to an even higher number of SNPs with odds ratios smaller than 1.1. Recent studies have provided the following information: (1) The functions of genes identified as relevant for bladder cancer focus on detoxification of carcinogens, control of the cell cycle and apoptosis, as well as maintenance of DNA integrity. (2) Many novel SNPs are far away from the protein coding regions, suggesting that these SNPs are located on distant-acting transcriptional enhancers. (3) The low odds ratio of each individual bladder cancer-associated SNP is too low to justify reasonable preventive measures. However, if the recently identified SNPs interact, they may

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

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    Peng Li

    2017-02-01

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

  8. Radical cystectomy for bladder cancer:oncologic outcome in 271 Chinese patients

    Institute of Scientific and Technical Information of China (English)

    Zhi-Ling Zhang; Pei Dong; Yong-Hong Li; Zhuo-Wei Liu; Kai Yao; Hui Han; Zi-Ke Qin; Fang-Jian Zhou

    2014-01-01

    Few large scale studies have reported the oncologic outcome of radical cystectomy for treating bladder cancer in China; hence, we lack long-term prognostic information. The aim of the current study was to determine the survival rate and prognostic factors of patients who underwent radical cystectomy for bladder cancer in a Chinese medical center. We retrospectively analyzed clinicopathologic data from 271 bladder cancer patients who underwent radical cystectomy between 2000 and 2011. Univariate and multivariate analyses were conducted to identify independent prognostic predictors for this cohort. Median follow-up was 31.7 months (range, 0.2-139.1 months). Thirty-day mortality was (1.4%). The 5-year recurrence-free survival, cancer-specific survival (CSS), and overall survival rates were 61.6%, 72.9%, and 68.0%, respectively. The 5-year CSS rates of patients with T1-T4 disease were 90.7%, 85.0%, 51.0%, and 18.0%, respectively. Patients with organ-confined disease had a higher 5-year CSS rate than those with extravesical disease (81.4%vs. 34.9%, P<0.001). For the 38 patients (14%) with lymph node involvement, the 5-year CSS rate was 27.7%-significantly lower than that of patients without lymph node metastasis (P < 0.001). The 5-year CSS rate was much higher in patients with low grade tumor than in those with high grade tumor (98.1%vs. 68.1%, P<0.001). Multivariate Cox regression showed that patient age (hazard ratio, 2.045; P = 0.013) and T category (hazard ratio, 2.213; P < 0.001) were independent predictors for CSS. These results suggest that radical cystectomy is a safe and effective method for treating bladder cancer in Chinese patients. Old age and high T category were associated with poor prognosis in bladder cancer patients who underwent radical cystectomy.

  9. Surface membrane based bladder registration for evaluation of accumulated dose during brachytherapy in cervical cancer

    DEFF Research Database (Denmark)

    Noe, Karsten Østergaard; Tanderup, Kari; Sørensen, Thomas Sangild

    2011-01-01

    of the fixed surface. Optional landmark based matches can be included in the suggested iterative solver. The technique is demonstrated for bladder registration in brachytherapy treatment evaluation of cervical cancer. It holds promise to better estimate the accumulated but unintentional dose delivered...

  10. Penile metastasis secondary to bladder cancer: A report of two cases

    Directory of Open Access Journals (Sweden)

    Narendra Kumar

    2014-01-01

    Full Text Available Penile metastasis secondary to primary bladder cancer is a rare entity and represents a challenging problem. The common mode of spread to the penis is by retrograde venous route. The overall outcome is dismal and most patients will die within 1 year even after optimum treatment. Here, we report two such cases.

  11. Defining progression in nonmuscle invasive bladder cancer: it is time for a new, standard definition

    NARCIS (Netherlands)

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

    2014-01-01

    PURPOSE: Despite being one of the most important clinical outcomes in nonmuscle invasive bladder cancer, there is currently no standard definition of disease progression. Major clinical trials and meta-analyses have used varying definitions or have failed to define this end point altogether. A stand

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

    Pedersen, Marie; Stafoggia, Massimo; Weinmayr, Gudrun

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-05-07

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  17. Detection of penile metastasis from bladder cancer using F 18 FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong Yun; Lee, Jong Jin [Univ. of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2012-12-15

    A 74 year old man who had experienced priapism for 2 months after radical cystectomy for bladder cancer visited our hospital, and underwent metastatic work up {sup 18}F fluorodeoxyglucose (FDG) positron emission tomography/computed tomography(PET/CT)showed diffuse hypermetabolic activity along the penis shaft, which was confirmed as a penile metastasis.

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

    Science.gov (United States)

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

    2014-01-01

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

  19. Evaluation of tissue and urinary survivin expression in non-muscle-invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    S. Sharaf

    2012-12-01

    Conclusion: Urinary survivin is a useful marker for non-invasive detection of non-muscle-invasive bladder cancer recurrence. Its detection is better using ELISA technique than WB and there is no correlation between its expression in tissue and urine.

  20. Sequence variant on 8q24 confers susceptibility to urinary bladder cancer.

    NARCIS (Netherlands)

    Kiemeney, L.A.L.M.; Thorlacius, S.; Sulem, P.; Geller, F.; Aben, K.K.H.; Stacey, S.N.; Gudmundsson, J.; Jakobsdottir, M.; Bergthorsson, J.T.; Sigurdsson, A.; Blondal, T.; Witjes, J.A.M.; Vermeulen, H.H.M.; Hulsbergen- van de Kaa, C.A.; Swinkels, D.W.; Ploeg, M.; Cornel, E.B.; Vergunst, H.; Thorgeirsson, T.E.; Gudbjartsson, D.; Gudjonsson, S.A.; Thorleifsson, G.; Kristinsson, K.T.; Mouy, M.; Snorradottir, S.; Placidi, D.; Campagna, M.; Arici, C.; Koppova, K.; Gurzau, E.; Rudnai, P.; Kellen, E.; Polidoro, S.; Guarrera, S.; Sacerdote, C.; Sanchez, M.; Saez, B.; Valdivia, G.; Ryk, C.; Verdier, P de; Lindblom, A.; Golka, K.; Bishop, D.T.; Knowles, M.A.; Nikulasson, S.; Petursdottir, V.; Jonsson, E.; Geirsson, G.; Kristjansson, B.; Mayordomo, J.I.; Steineck, G.; Porru, S.; Buntinx, F.; Zeegers, M.P.; Fletcher, T.; Kumar, R.; Matullo, G.; Vineis, P.; Kiltie, A.E.; Gulcher, J.R.; Thorsteinsdottir, U.; Kong, A.; Rafnar, T.; Stefansson, K.

    2008-01-01

    We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  2. Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A major problem which is poorly understood in the management of bladder cancer is low sensitivity to chemotherapy and high recurrence after transurethral resection.Insulin-like growth factor 1 receptor(IGF-1R)signaling plays a very important role in progression,invasion and metastasis of bladder cancer cells.In this study,we investigated whether IGF-1R was involved in the growth stimulating activity and drug resistance of bladder cancer cells.The results showed: The mRNAs of IGF-1,IGF-2 and IGF-1R were strongly expressed in serum-free cultured T24 cell line,whereas normal urothelial cells did not express these factors/receptors or only in trace levels; T24 cell responded far better to growth stimulation by IGF-1 than did normal urothelial cells; blockage of IGF1R by antisense oligodeoxynucleotide(ODN)significantly inhibited the growth of T24 cell and enhanced sensitivity and apoptosis of T24 cells to mitomycin(MMC).These results suggested that blockage of IGF-IR signaling might potentially contribute to the treatment of bladder cancer cells which are insensitive to chemotherapy.

  3. Electroporation enhances mitomycin C cytotoxicity on T24 bladder cancer cell line

    DEFF Research Database (Denmark)

    Vasquez, Juan Luis; Gehl, Julie; Hermann, Gregers G

    2012-01-01

    improves the cytotoxicity of mitomycin. In two cell lines, T24 (bladder cancer cell line) and DC3F (Chinese hamster fibroblast), exposure to different concentrations of mitomycin (0.01-2000μM) was tested with and without electroporation (6 pulses of 1kV/cm, duration: 99μs, frequency: 1Hz). Cell viability...

  4. MOLECULAR MARKERS OF BLADDER CANCER: FROM THE PARTICULAR TO THE GENERAL

    Directory of Open Access Journals (Sweden)

    A. A. Zabolotneva

    2014-08-01

    Full Text Available Bladder cancer (BC is the second most common urinary tract malignancy. Early diagnosis of BC generally increases the probability of successful treatment in a patient. The paper considers noninvasive diagnosis methods for BC and gives a database of the known molecular markers of this disease.

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

    Science.gov (United States)

    Dong, Youhong; Wang, Anping

    2016-07-01

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

  6. Ginkgolide B Inhibits Human Bladder Cancer Cell Migration and Invasion Through MicroRNA-223-3p

    Directory of Open Access Journals (Sweden)

    Yi Zhi

    2016-10-01

    Full Text Available Background/Aims: Ginkgolide B (GB is currently used as an anticancer drug for treatment of some malignant cancers. However, whether it may have therapeutic effects on bladder cancer remains unknown. Here, we studied the effects of GB on bladder cancer cells. Methods: Bladder cells were treated with different doses of GB, and the effects on ZEB1 and microRNA-223-3p (miR-223-3p were analyzed by RT-qPCR and/or Western blot. Prediction of a regulatory relationship between miR-93 and 3'-UTR of Beclin-1 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Results: We found that GB dose-dependently decreased ZEB1 protein, but not mRNA, in bladder cancer cells, resulting in suppression of cell invasion. Moreover, in bladder cancer cells, GB dose-dependently decreased the levels of miR-223-3p, which suppressed the protein translation of ZEB1 through binding to 3'-UTR of ZEB1 mRNA. Overexpression of miR-223-3p decreased ZEB1 protein, while depletion of miR-223-3p increased ZEB1 protein in bladder cancer cells. Conclusion: GB inhibits bladder cancer cell invasiveness through suppressing ZEB1 protein translation via upregulating miR-223-3p.

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

    Science.gov (United States)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Doğan Değer

    2017-03-01

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

  10. Mycotic aneurysm of the popliteal artery as a complication of intravesical BCG therapy for superficial bladder cancer. Case report and literature review.

    NARCIS (Netherlands)

    Witjes, J.A.; Vriesema, J.L.J.; Brinkman, K.; Bootsma, G.P.; Barentsz, J.O.

    2003-01-01

    A 67-year-old man was treated with maintenance intravesical BCG for superficial bladder cancer. As a culture-proven complication of this therapy, he developed general malaise, high fever, granulomatous hepatitis and a mycotic aneurysm in his left knee. All complications were treated successfully wit

  11. Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Reinert, Thomas; Novoradovsky, A;

    2012-01-01

    Background: Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. Meth...

  12. Tumor regression grade of urothelial bladder cancer after neoadjuvant chemotherapy: a novel and successful strategy to predict survival.

    OpenAIRE

    Fleischmann, Achim; Thalmann, George; Perren, Aurel; Seiler,Roland

    2014-01-01

    Histopathologic tumor regression grades (TRGs) after neoadjuvant chemotherapy predict survival in different cancers. In bladder cancer, corresponding studies have not been conducted. Fifty-six patients with advanced invasive urothelial bladder cancer received neoadjuvant chemotherapy before cystectomy and lymphadenectomy. TRGs were defined as follows: TRG1: complete tumor regression; TRG2: >50% tumor regression; TRG3: 50% or less tumor regression. Separate TRGs were assigned for primary tumor...

  13. Applications of chemotherapy in muscle invasive bladder cancer with bladder preservation%应重视化疗在肌层浸润性膀胱癌保留膀胱治疗中的作用

    Institute of Scientific and Technical Information of China (English)

    田野

    2014-01-01

    Chemotherapy has been developing to be an important adjuvant treatment methods in treatment of muscle invasive bladder cancer in recent years. Such method is meaningful for patients who want to preserve the bladder. The author summarized the role and effect of neoadjuvant chemotherapy and adjuvant chemotherapy. This article reviews the methods and effect of radical transurethral resection of bladder tumor with chemotherapy and partial cystectomy with chemotherapy. Data of several special patients including patients with renal transplantation and dialysis patients undergoing chemotherapy are presented. The problems existing in current drug sensitivity of chemotherapy are discussed finally. The future of chemotherapy in muscle invasive bladder cancer with bladder preservation is predicted.%化疗是近年来肌层浸润性膀胱癌重要的辅助治疗手段,对于临床要求保留膀胱的患者意义重大。本文介绍了新辅助化疗和辅助化疗的作用及效果,对经尿道根治性膀胱肿瘤切除术(transurethral resection of bladder tumor,TURBT)联合化疗以及膀胱部分切除术联合化疗的方法及疗效进行综述,同时对一些特殊患者例如肾脏移植患者及透析患者的化疗进行了介绍;最后对当前化疗中存在的药物敏感性问题加以阐述,并对今后化疗在肌层浸润性膀胱癌保留膀胱的发展前景进行了展望。

  14. Optimal control on bladder cancer growth model with BCG immunotherapy and chemotherapy

    Science.gov (United States)

    Dewi, C.; Trisilowati

    2015-03-01

    In this paper, an optimal control model of the growth of bladder cancer with BCG (Basil Calmate Guerin) immunotherapy and chemotherapy is discussed. The purpose of this optimal control is to determine the number of BCG vaccine and drug should be given during treatment such that the growth of bladder cancer cells can be suppressed. Optimal control is obtained by applying Pontryagin principle. Furthermore, the optimal control problem is solved numerically using Forward-Backward Sweep method. Numerical simulations show the effectiveness of the vaccine and drug in controlling the growth of cancer cells. Hence, it can reduce the number of cancer cells that is not infected with BCG as well as minimize the cost of the treatment.

  15. Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises.

    Science.gov (United States)

    Aragon-Ching, Jeanny B; Trump, Donald L

    2016-09-01

    Bladder urothelial cancers remain an important urologic cancer with limited treatment options in the locally advanced and metastatic setting. While neoadjuvant chemotherapy for locally advanced muscle-invasive cancers has shown overall survival benefit, clinical uptake in practice have lagged behind. Controversies surrounding adjuvant chemotherapy use are also ongoing. Systemic therapies for metastatic bladder cancer have largely used platinum-based therapies without effective standard second-line therapy options for those who fail, although vinflunine is approved in Europe as a second-line therapy based on a Phase III trial, and most recently, atezolizumab, a checkpoint inhibitor, was approved by the US FDA. Given increasing recognition of mutational signatures expressed in urothelial carcinomas, several promising agents with use of VEGF-targeted therapies, HER2-directed agents and immunotherapies with PD-1/PD-L1 antibodies in various settings are discussed herein.

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

    Science.gov (United States)

    Raimondi, Cristina; Gradilone, Angela; Gazzaniga, Paola

    2014-05-01

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

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

    Science.gov (United States)

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

    2003-10-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Bigio, I.J.; Mourant, J.R.; Boyer, J.; Johnson, T.; Shimada, T. [Los Alamos National Lab., NM (United States); Conn, R.L. [Lovelace Medical Center, Albuquerque, NM (United States). Dept. of Urology

    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.

  19. Electroporation enhances mitomycin C cytotoxicity on T24 bladder cancer cell line: a potential improvement of intravesical chemotherapy in bladder cancer.

    Science.gov (United States)

    Vásquez, Juan L; Gehl, Julie; Hermann, Gregers G

    2012-12-01

    Intravesical mitomycin instillation combined with electric pulses is being used experimentally for the treatment of T1 bladder tumors, in patients unfit for surgery. Electroporation may enhance the uptake of chemotherapeutics by permeabilization of cell membranes. We investigated if electroporation improves the cytotoxicity of mitomycin. In two cell lines, T24 (bladder cancer cell line) and DC3F (Chinese hamster fibroblast), exposure to different concentrations of mitomycin (0.01-2000μM) was tested with and without electroporation (6 pulses of 1kV/cm, duration: 99μs, frequency: 1Hz). Cell viability was assessed by colorimetric assay (MTT). For both cell lines, mitomycin's IC_50 was approximately 1000μM in both pulsed and unpulsed cells. On T24 cells, electroporation and mitomycin caused (relative reduction) RR of survival of: 25%, 31% and 29%, by concentrations 0μM, 500μM and 1000μM respectively. For DC3F cells, the RRs of survival were: 28%, 29%, and 33%, by concentrations 0μM, 500μM and 1000μM respectively. In conclusion, electroporation and mitomycin together are about 30% more effective than mitomycin alone. The results help to elucidate the additive effect of mitomycin and electric pulses and support the use of this combination in the treatment of bladder cancer.

  20. Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth

    Directory of Open Access Journals (Sweden)

    Claudia Ceci

    2016-11-01

    Full Text Available Ellagic acid (EA is a polyphenolic compound that can be found as a naturally occurring hydrolysis product of ellagitannins in pomegranates, berries, grapes, green tea and nuts. Previous studies have reported the antitumor properties of EA mainly using in vitro models. No data are available about EA influence on bladder cancer cell invasion of the extracellular matrix triggered by vascular endothelial growth factor-A (VEGF-A, an angiogenic factor associated with disease progression and recurrence, and tumor growth in vivo. In this study, we have investigated EA activity against four different human bladder cancer cell lines (i.e., T24, UM-UC-3, 5637 and HT-1376 by in vitro proliferation tests (measuring metabolic and foci forming activity, invasion and chemotactic assays in response to VEGF-A and in vivo preclinical models in nude mice. Results indicate that EA exerts anti-proliferative effects as a single agent and enhances the antitumor activity of mitomycin C, which is commonly used for the treatment of bladder cancer. EA also inhibits tumor invasion and chemotaxis, specifically induced by VEGF-A, and reduces VEGFR-2 expression. Moreover, EA down-regulates the expression of programmed cell death ligand 1 (PD-L1, an immune checkpoint involved in immune escape. EA in vitro activity was confirmed by the results of in vivo studies showing a significant reduction of the growth rate, infiltrative behavior and tumor-associated angiogenesis of human bladder cancer xenografts. In conclusion, these results suggest that EA may have a potential role as an adjunct therapy for bladder cancer.

  1. Genotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer.

    Directory of Open Access Journals (Sweden)

    Uzma Shahab

    Full Text Available BACKGROUND: The interaction of environmental chemicals and their metabolites with biological macromolecules can result in cytotoxic and genotoxic effects. 4-Aminobiphenyl (4-ABP and several other related arylamines have been shown to be causally involved in the induction of human urinary bladder cancers. The genotoxic and the carcinogenic effects of 4-ABP are exhibited only when it is metabolically converted to a reactive electrophile, the aryl nitrenium ions, which subsequently binds to DNA and induce lesions. Although several studies have reported the formation of 4-ABP-DNA adducts, no extensive work has been done to investigate the immunogenicity of 4-ABP-modified DNA and its possible involvement in the generation of antibodies in bladder cancer patients. METHODOLOGY/PRINCIPAL FINDINGS: Human DNA was modified by N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP, a reactive metabolite of 4-ABP. Structural perturbations in the N-OH-AABP modified DNA were assessed by ultraviolet, fluorescence, and circular dichroic spectroscopy as well as by agarose gel electrophoresis. Genotoxicity of N-OH-AABP modified DNA was ascertained by comet assay. High performance liquid chromatography (HPLC analysis of native and modified DNA samples confirmed the formation of N-(deoxyguanosine-8-yl-4-aminobiphenyl (dG-C8-4ABP in the N-OH-AABP damaged DNA. The experimentally induced antibodies against N-OH-AABP-modified DNA exhibited much better recognition of the DNA isolated from bladder cancer patients as compared to the DNA obtained from healthy individuals in competitive binding ELISA. CONCLUSIONS/SIGNIFICANCE: This work shows epitope sharing between the DNA isolated from bladder cancer patients and the N-OH-AABP-modified DNA implicating the role of 4-ABP metabolites in the DNA damage and neo-antigenic epitope generation that could lead to the induction of antibodies in bladder cancer patients.

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

    Science.gov (United States)

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

    2007-07-01

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

  3. Comparison of virtual cystoscopy and ultrasonography for bladder cancer detection: A meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Qu Xinhua; Huang Xiaolu [Department of Nuclear Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127 (China); Department of Ultrasonic, Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011 (China); Wu Lianming [Department of Radiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127 (China); Huang Gang [Department of Nuclear Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127 (China); Ping Xiong, E-mail: pxiong6@126.com [Department of Ultrasonic, Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011 (China); Yan Weili, E-mail: wl_yan67@126.com [Department of Nuclear Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127 (China)

    2011-11-15

    Background and purpose: Bladder cancer is the most commonly diagnosed malignancy in patients presenting with haematuria. Early detection is crucial for improving patient prognosis. We therefore performed a meta-analysis to evaluate and compare the detection validity (sensitivity and specificity) of virtual cystoscopy (VC) and ultrasonography (US). Methods: We searched MEDLINE, EMBASE, PubMed and the Cochrane Library for studies evaluating diagnosis validity of VC and US between January 1966 and December 2009. Meta-analysis methods were used to pool sensitivity and specificity and to construct a summary receiver-operating characteristic (SROC) curve. Results: A total of 26 studies that included 3084 patients who fulfilled all of the inclusion criteria were considered for inclusion in the analysis. The pooled sensitivity for bladder cancer detection using CT virtual cystoscopy (CTVC), MR virtual cystoscopy (MRVC) and US was 0.939 (95% CI, 0.919-0.956), 0.908 (95% CI, 0.827-0.959) and 0.779 (95% CI, 0.744-0.812), respectively. The pooled specificity for bladder cancer detection using CTVC, MRVC and US was 0.981 (95% CI, 0.973-0.988), 0.948 (95% CI, 0.884-0.983) and 0.962 (95% CI, 0.953-0.969), respectively. The pooled diagnostic odd ratio (DOR) estimate for CTVC (604.22) were significantly higher than for MRVC (144.35, P < 0.001) and US (72.472, P < 0.001). Conclusion: Our results showed that both CTVC and MRVC are better imaging methods for diagnosing bladder cancer than US. CTVC has higher diagnostic value (sensitivity, specificity and DOR) for the detection of bladder cancer than either MRCT or US.

  4. Estimating water supply arsenic levels in the New England bladder cancer study

    Science.gov (United States)

    Nuckols, John R.; Beane Freeman, Laura E.; Lubin, Jay H.; Airola, Matthew S.; Baris, Dalsu; Ayotte, Joseph D.; Taylor, Anne; Paulu, Chris; Karagas, Margaret R.; Colt, Joanne; Ward, Mary H.; Huang, An-Tsun; Bress, William; Cherala, Sai; Silverman, Debra T.; Cantor, Kenneth P.

    2011-01-01

    Background: Ingestion of inorganic arsenic in drinking water is recognized as a cause of bladder cancer when levels are relatively high (≥ 150 μg/L). The epidemiologic evidence is less clear at the low-to-moderate concentrations typically observed in the United States. Accurate retrospective exposure assessment over a long time period is a major challenge in conducting epidemiologic studies of environmental factors and diseases with long latency, such as cancer.

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

    Science.gov (United States)

    2010-03-01

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

  6. BCG Induced Necrosis of the Entire Bladder Urothelium

    Directory of Open Access Journals (Sweden)

    Malte Krönig

    2015-09-01

    Full Text Available Instillation therapy with attenuated tuberculosis bacteria (BCG can significantly reduce rates of recurrence of non-muscle invasive bladder cancer. Local and systemic side effects such as dysuria, irritative voiding symptoms or partial bladder contracture and systemic inflammation were reported. A 75 year-old male patient with recurrent non muscle invasive bladder cancer developed necrosis of the entire bladder urothelium more than six years after BCG instillation immunotherapy. The resulting irritative voiding symptoms and low bladder capacity required radical cystectomy. BCG instillation can cause severe side effects, which develop gradually and eventually need radical surgical therapy such as cystectomy without tumor recurrence.

  7. Immunohistochemical study of the expression of cell cycle regulating proteins at different stages of bladder cancer

    DEFF Research Database (Denmark)

    Primdahl, Hanne; Maase, Hans von der; Sørensen, Flemming B.

    2002-01-01

    PURPOSE: The cell cycle is known to be deregulated in cancer. We therefore analyzed the expression of the cell cycle related proteins p21, p27, p16, Rb, and L-myc by immunohistochemical staining of bladder tumors. METHODS: The tissue material consisted of bladder tumors from three groups......(kip1) ( P=0.03), Rb ( P=0.00002), and L-myc ( P=0.00000007) in muscle invasive tumors compared to noninvasive tumors. Tumors presenting as muscle invasive at first diagnosis had significantly lower levels of p16/CDKN2A ( P=0.01) when compared to muscle invasive tumors that followed Ta or T1 precursor...

  8. Sequence variant on 8q24 confers susceptibility to urinary bladder cancer

    Science.gov (United States)

    Kiemeney, Lambertus A.; Thorlacius, Steinunn; Sulem, Patrick; Geller, Frank; Aben, Katja K.H.; Stacey, Simon N.; Gudmundsson, Julius; Jakobsdottir, Margret; Bergthorsson, Jon T.; Sigurdsson, Asgeir; Blondal, Thorarinn; Witjes, J. Alfred; Vermeulen, Sita H.; Hulsbergen-van de Kaa, Christina A.; Swinkels, Dorine W.; Ploeg, Martine; Cornel, Erik B.; Vergunst, Henk; Thorgeirsson, Thorgeir E.; Gudbjartsson, Daniel; Gudjonsson, Sigurjon A.; Thorleifsson, Gudmar; Kristinsson, Kari T.; Mouy, Magali; Snorradottir, Steinunn; Placidi, Donatella; Campagna, Marcello; Arici, Cecilia; Koppova, Kvetoslava; Gurzau, Eugene; Rudnai, Peter; Kellen, Eliane; Polidoro, Silvia; Guarrera, Simonetta; Sacerdote, Carlotta; Sanchez, Manuel; Saez, Berta; Valdivia, Gabriel; Ryk, Charlotta; de Verdier, Petra; Lindblom, Annika; Golka, Klaus; Bishop, D. Timothy; Knowles, Margaret A.; Nikulasson, Sigfus; Petursdottir, Vigdis; Jonsson, Eirikur; Geirsson, Gudmundur; Kristjansson, Baldvin; Mayordomo, Jose I.; Steineck, Gunnar; Porru, Stefano; Buntinx, Frank; Zeegers, Maurice P.; Fletcher, Tony; Kumar, Rajiv; Matullo, Giuseppe; Vineis, Paolo; Kiltie, Anne E.; Gulcher, Jeffrey R.; Thorsteinsdottir, Unnur; Kong, Augustine; Rafnar, Thorunn; Stefansson, Kari

    2015-01-01

    We conducted a genome wide SNP association study on 1,803 Urinary Bladder Cancer (UBC) cases and 34,336 controls from Iceland and the Netherlands and follow up studies in seven additional case control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30kb upstream of the c-Myc gene (allele specific OR=1.22; P=9.34×10−12). Approximately 20% of individuals of European ancestry are homozygous for rs9642880 (T) and their estimated risk of developing UBC is 1.49 times that of non-carriers with population attributable risk (PAR) of 17%. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome wide significance, was captured by rs710521 (A) located near the TP63 gene on chromosome 3q28 (allele specific OR=1.19; P=1. 15× 10−7). PMID:18794855

  9. Identification and characterization of DNAzymes targeting DNA methyltransferase I for suppressing bladder cancer proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiangbo; Zhang, Lu; Ding, Nianhua; Yang, Xinghui; Zhang, Jin; He, Jiang; Li, Zhi; Sun, Lun-Quan, E-mail: lunquansun@csu.edu.cn

    2015-05-29

    Epigenetic inactivation of genes plays a critical role in many important human diseases, especially in cancer. A core mechanism for epigenetic inactivation of the genes is methylation of CpG islands in genome DNA, which is catalyzed by DNA methyltransferases (DNMTs). The inhibition of DNMTs may lead to demethylation and expression of the silenced tumor suppressor genes. Although DNMT inhibitors are currently being developed as potential anticancer agents, only limited success is achieved due to substantial toxicity. Here, we utilized a multiplex selection system to generate efficient RNA-cleaving DNAzymes targeting DNMT1. The lead molecule from the selection was shown to possess efficient kinetic profiles and high efficiency in inhibiting the enzyme activity. Transfection of the DNAzyme caused significant down-regulation of DNMT1 expression and reactivation of p16 gene, resulting in reduced cell proliferation of bladder cancers. This study provides an alternative for targeting DNMTs for potential cancer therapy. - Highlights: • Identified DNMT1-targeted DNAzymes by multiplex selection system. • Biochemically characterized a lead DNAzyme with high kinetic efficiency. • Validated DNMT1-targeted DNAzyme in its enzymatic and cellular activities.

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

    Science.gov (United States)

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

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Minna M Boström

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

  12. Comparison of post contrast CT urography phases in bladder cancer detection

    Energy Technology Data Exchange (ETDEWEB)

    Helenius, Malin; Dahlman, Par; Lonnemark, Maria; Magnusson, Anders [Uppsala University Hospital, Department of Surgical Sciences, Section of Radiology, Uppsala (Sweden); Brekkan, Einar [Uppsala University Hospital, Department of Surgical Sciences, Section of Urology, Uppsala (Sweden); Wernroth, Lisa [Uppsala University Hospital, Uppsala Clinical Research Center, Uppsala (Sweden)

    2016-02-15

    The aim of this study was to investigate which post-contrast phase(s) in a four-phase CT urography protocol is (are) most suitable for bladder cancer detection. The medical records of 106 patients with visible haematuria who underwent a CT urography examination, including unenhanced, enhancement-triggered corticomedullary (CMP), nephrographic (NP) and excretory (EP) phases, were reviewed. The post-contrast phases (n = 318 different phases) were randomized into an evaluation order and blindly reviewed by two uroradiologists. Twenty-one patients were diagnosed with bladder cancer. Sensitivity for bladder cancer detection was 0.95 in CMP, 0.83 in NP and 0.81 in EP. Negative predictive value (NPV) was 0.99 in CMP, 0.96 in NP and 0.95 in EP. The sensitivity was higher in CMP than in both NP (p-value 0.016) and EP (p-value 0.0003). NPV was higher in CMP than in NP (p-value 0.024) and EP (p-value 0.002). In the CT urography protocol with enhancement-triggered scan, sensitivity and NPV were highest in the corticomedullary phase, and this phase should be used for bladder assessment. (orig.)

  13. Intracavitary cobalt-60 irradiation in the prophylactic treatment of bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Tadashi; Kigure, Teruaki; Miyagata, Shigeru (Akita Univ. (Japan). School of Medicine) (and others)

    1992-05-01

    This paper describes the technique and preliminary clinical results of transurethral intracavitary whole bladder mucosal irradiation (IWI) for the prophylaxis of bladder cancer. In this procedure, first, the balloon catheter (22 Fr.) is inserted into the bladder, and next the balloon is inflated with 100 ml of air. Then a Co-60 pellet with about 110 GBq of activity is driven into the center of the bladder. With this method, we can irradiate the whole bladder mucosa almost equally. From April 1985, 36 patients with recurrent tumor and 26 patients with primary and multiple tumors of the bladder have been treated with IWI after transurethral resection or microwave coagulation of the tumors. Tumor stage and grade were as follows: Tis (7), T{sub a}, T{sub 1} (41), T{sub 2} (14), G1 (16), G2 (30) and G3 (16). The tumors were transitional cell carcinoma in all patients. IWI was performed once a week, usually 3 to 5 times, depending on the patients. The total dose to the bladder mucosa ranged from 20 to 58.5 Gy with an average dose of 37.6 Gy. Recurrence rates before and after IWI were calculated using the following formula: recurrence rates (RR)=(total number of recurrences/total months of follow up)x100. RR in the 36 patients with recurrent tumor was 14.0 before IWI and 1.8 after IWI (mean follow up 37.6 mos.). RR in the 26 patients with multiple tumors was 1.4 after IWI (mean follow up 34.8 mos.). RR in patients with G1, G2 and G3 tumors were 1.2, 1.7 and 2.2. The most common side effect was temporary urinary frequency observed in 36 patients (52.9%). Three patients had contracted bladder, and two had hydronephrosis. However, proctitis or incontinence was not evident. Although the preliminary clinical results suggest that our new technique is an effective prophylactic treatment for bladder cancer, further investigation is needed to determine its efficacy. (author).

  14. Bilateral ureteral complete obstruction with huge spontaneous urinoma formation in a patient with advanced bladder cancer.

    Science.gov (United States)

    Jou, Yeong-Chin; Shen, Cheng-Huang; Cheng, Ming-Chin; Lin, Chang-Te; Chen, Pi-Che

    2012-02-01

    Spontaneous rupture of the collecting system with extravasation of urine and urinoma formation is usually associated with urinary tract obstruction by a ureteral calculus. Tumor growth is an extremely rare cause of urinary extravasation. Here we report a case of bilateral obstructive uropathy with a huge spontaneous left retroperitoneal urinoma caused by advanced infiltrative transitional cell carcinoma of the urinary bladder. The point of leakage was located in the left renal pelvis. The urinary leakage ceased after percutaneous nephrostomy drainage, and the patient subsequently underwent radical cystoprostatectomy. Histopathology revealed a high-grade urothelial carcinoma of the urinary bladder with pelvic lymph node metastasis. The patient refused any adjuvant treatment and expired 6 months after the operation from disseminated metastasis from bladder cancer.

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

    Directory of Open Access Journals (Sweden)

    A.P.M. van der Meijden

    2006-01-01

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

  16. 1α,25(OH)2D3 differentially regulates miRNA expression in human bladder cancer cells.

    Science.gov (United States)

    Ma, Yingyu; Hu, Qiang; Luo, Wei; Pratt, Rachel N; Glenn, Sean T; Liu, Song; Trump, Donald L; Johnson, Candace S

    2015-04-01

    Bladder cancer is the fourth most commonly diagnosed cancer in men and eighth leading cause of cancer-related death in the US. Epidemiological and experimental studies strongly suggest a role for 1α,25(OH)2D3 in cancer prevention and treatment. The antitumor activities of 1α,25(OH)2D3 are mediated by the induction of cell cycle arrest, apoptosis, differentiation and the inhibition of angiogenesis and metastasis. miRNAs play important regulatory roles in cancer development and progression. However, the role of 1α,25(OH)2D3 in the regulation of miRNA expression and the potential impact in bladder cancer has not been investigated. Therefore, we studied 1α,25(OH)2D3-regulated miRNA expression profiles in human bladder cancer cell line 253J and the highly tumorigenic and metastatic derivative line 253J-BV by miRNA qPCR panels. 253J and 253J-BV cells express endogenous vitamin D receptor (VDR), which can be further induced by 1α,25(OH)2D3. VDR target gene 24-hydroxylase was induced by 1α,25(OH)2D3 in both cell lines, indicating functional 1α,25(OH)2D3 signaling. The miRNA qPCR panel assay results showed that 253J and 253J-BV cells have distinct miRNA expression profiles. Further, 1α,25(OH)2D3 differentially regulated miRNA expression profiles in 253J and 253J-BV cells in a dynamic manner. Pathway analysis of the miRNA target genes revealed distinct patterns of contribution to the molecular functions and biological processes in the two cell lines. In conclusion, 1α,25(OH)2D3 differentially regulates the expression of miRNAs, which may contribute to distinct biological functions, in human bladder 253J and 253J-BV cells. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

  17. XIAP as a prognostic marker of early recurrence of nonmuscular invasive bladder cancer

    Institute of Scientific and Technical Information of China (English)

    LI Ming; SONG Tao; YIN Zhen-fei; NA Yan-qun

    2007-01-01

    Background Dysregulation of apoptosis has been implicated not only in carcinogenesis and tumor progression but also in tumor recurrence. We investigated whether the expression of X-linked inhibitor of apoptosis (XIAP) might predict early recurrence in patients with non-muscular invasive bladder cancer.Methods The cohort comprised 176 consecutive patients with primary superficial bladder cancer treated with transurethral resection. Immunohistochemical staining using the standard avidin-biotin-peroxidase technique and RT-PCR were used to detect XIAP protein and mRNA expressions in cancer tissues. The relationship between XIAP expression and clinicopathological characteristics, cancer recurrence were analyzed.Results XIAP expression was observed in 108 cases (61.4%) and no expression in 68. There was no correlation between XIAP expression rate and the tumor pathological grade, but was an apparent trend toward the increased XIAP levels from well (G1) to poor (G3) differentiated cancer. Eighty-two (46.6%) patients experienced tumor recurrence at a mean of 28.6 months of the follow-up; 66 of them expressed XIAP (61.1%) and 16 were XIAP negative (23.5%). Twelve patients presented with invasive disease at the time of relapse and all of them expressed XIAP. Patients without XIAP expression or with low tumor grades had significantly higher recurrence-free survival than those with XIAP expression(log rank test P=0.0015) or high tumor grades (log rank test P<0.001). Multivariate analysis revealed that XIAP expression, tumor grade, and tumor number were independent predictors for the recurrence of non-muscular invasive bladder cancer (P=-0.004, 0.016, and 0.043, respectively).Conclusions XIAP may be considered as a new independent prognostic marker for early recurrence of non-muscular invasive bladder cancer.

  18. Schistosomiasis mansoni of the bladder simulating bladder cancer: a case report Esquistossomose mansônica simulando câncer de bexiga: relato de caso

    Directory of Open Access Journals (Sweden)

    Mário Luis Casella

    2009-10-01

    Full Text Available The relationship between bladder tumors and Schistosoma haematobium is well known, but only sporadic cases of bladder infection due to Schistosoma mansoni have been reported. In this case, a 48-year-old woman with macroscopic hematuria, dysuria and a palpable abdominal mass was investigated. Ultrasound showed a large exophytic mass in the bladder. Transurethral resection of the bladder revealed viable eggs of Schistosoma mansoni. The patient was treated clinically with oxamniquine and surgery was performed to resect the large mass. This case shows that schistosomiasis Mansoni in the bladder can simulate bladder cancer.É bem conhecida a relação entre tumor vesical e Schistosoma haematobium, porém somente casos esporádicos de infecção vesical por Schistosoma mansoni foram relatados. Neste caso, uma mulher de 48 anos com hematúria macroscópica, disúria e massa abdominal palpável foi investigada, ultra-sonografia mostrou uma grande massa exofítica na bexiga. A ressecção transuretral de bexiga evidenciou ovos viáveis de Schistosoma mansoni. A paciente foi tratada clinicamente com oxaminiquine e uma cirurgia foi realizada para ressecar a grande massa. Este caso mostra que a esquistossomose mansônica vesical pode simular um câncer vesical.

  19. The novel bladder preservation therapy BOAI-CDDP-radiation (OMC-regimen): a new treatment option for invasive bladder cancer patients with lymph node metastasis.

    Science.gov (United States)

    Azuma, Haruhito; Inamoto, Teruo; Takahara, Kiyoshi; Nomi, Hayahito; Hirano, Hajime; Ibuki, Naokazu; Uehara, Hiroshi; Komura, Kazumasa; Minami, Koichiro; Uchimoto, Taizo; Saito, Kenkichi; Takai, Tomoaki; Tanda, Naoki; Yamamoto, Kazuhiro; Narumi, Yoshihumi; Kiyama, Satoshi

    2014-06-01

    We have developed a novel bladder preservation therapy for patients with muscle-invasive bladder cancer and lymph node metastasis: balloon-occluded arterial infusion (BOAI) of cisplatin/gemcitabine, with concomitant hemodialysis and irradiation [the so-called 'OMC (Osaka Medical College) regimen']. The OMC regimen delivers an extremely high concentration of anticancer agent to the site of the tumor, as well as the pelvic area, without causing any adverse systemic effects. In this study, we investigated the efficiency of the OMC regimen in 34 patients who underwent BOAI with cisplatin (100, 200 or 300 mg) along with 60 Gy of irradiation; patients who failed to achieve CR underwent secondary BOAI with gemcitabine (1,600 mg). The overall clinical response was 73.5% (CR: 35.3%; PR: 17.6%; SD: 20.6%). The 5-year overall and progression-free survival rates were 54.4% and 52.5%, respectively. For treatment failure, N2 stage was selected as a significant risk factor by simple and multiple logistic regression analyses. Cox proportional hazards analyses showed that N2 stage, T4 stage and the presence of hydronephrosis were significant risk factors for overall survival. Indeed, 55.6% of patients with N1 stage achieved a complete response (CR) (vs. 12.5% for N2 patients, p=0.0151), and 90% (9/10) of the CR patients survived without recurrence with an intact bladder after a mean follow-up of 85 (range 7-193) weeks. The 3-year progrssion-free survival rate with an intact bladder was 65.8% (vs. 37.5% for N2, p=0.034), and the 5-year overall survival rate was 71.8% (vs. 30.6% for N2, p=0.004). No patients suffered severe toxicities of Grade II or more; the oldest patient, aged 85 years, successfully completed this therapy. In conclusion, the OMC regimen can be regarded as a new option for patients with macroscopic lymph node involvement, especially those at stage N1. Therapy will improve the feasibility of radical cure even without the need for cystectomy in patients for whom

  20. Whole-genome sequencing identifies genomic heterogeneity at a nucleotide and chromosomal level in bladder cancer

    Science.gov (United States)

    Morrison, Carl D.; Liu, Pengyuan; Woloszynska-Read, Anna; Zhang, Jianmin; Luo, Wei; Qin, Maochun; Bshara, Wiam; Conroy, Jeffrey M.; Sabatini, Linda; Vedell, Peter; Xiong, Donghai; Liu, Song; Wang, Jianmin; Shen, He; Li, Yinwei; Omilian, Angela R.; Hill, Annette; Head, Karen; Guru, Khurshid; Kunnev, Dimiter; Leach, Robert; Eng, Kevin H.; Darlak, Christopher; Hoeflich, Christopher; Veeranki, Srividya; Glenn, Sean; You, Ming; Pruitt, Steven C.; Johnson, Candace S.; Trump, Donald L.

    2014-01-01

    Using complete genome analysis, we sequenced five bladder tumors accrued from patients with muscle-invasive transitional cell carcinoma of the urinary bladder (TCC-UB) and identified a spectrum of genomic aberrations. In three tumors, complex genotype changes were noted. All three had tumor protein p53 mutations and a relatively large number of single-nucleotide variants (SNVs; average of 11.2 per megabase), structural variants (SVs; average of 46), or both. This group was best characterized by chromothripsis and the presence of subclonal populations of neoplastic cells or intratumoral mutational heterogeneity. Here, we provide evidence that the process of chromothripsis in TCC-UB is mediated by nonhomologous end-joining using kilobase, rather than megabase, fragments of DNA, which we refer to as “stitchers,” to repair this process. We postulate that a potential unifying theme among tumors with the more complex genotype group is a defective replication–licensing complex. A second group (two bladder tumors) had no chromothripsis, and a simpler genotype, WT tumor protein p53, had relatively few SNVs (average of 5.9 per megabase) and only a single SV. There was no evidence of a subclonal population of neoplastic cells. In this group, we used a preclinical model of bladder carcinoma cell lines to study a unique SV (translocation and amplification) of the gene glutamate receptor ionotropic N-methyl D-aspertate as a potential new therapeutic target in bladder cancer. PMID:24469795

  1. Androgenic dependence of exophytic tumor growth in a transgenic mouse model of bladder cancer: a role for thrombospondin-1

    Directory of Open Access Journals (Sweden)

    Yao Jorge L

    2008-04-01

    Full Text Available Abstract Background Steroid hormones influence mitogenic signaling pathways, apoptosis, and cell cycle checkpoints, and it has long been known that incidence of bladder cancer (BC in men is several times greater than in women, a difference that cannot be attributed to environmental or lifestyle factors alone. Castration reduces incidence of chemically-induced BC in rodents. It is unclear if this effect is due to hormonal influences on activation/deactivation of carcinogens or a direct effect on urothelial cell proliferation or other malignant processes. We examined the effect of castration on BC growth in UPII-SV40T transgenic mice, which express SV40 T antigen specifically in urothelium and reliably develop BC. Furthermore, because BC growth in UPII-SV40T mice is exophytic, we speculated BC growth was dependent on angiogenesis and angiogenesis was, in turn, androgen responsive. Methods Flat panel detector-based cone beam computed tomography (FPDCT was used to longitudinally measure exophytic BC growth in UPII-SV40T male mice sham-operated, castrated, or castrated and supplemented with dihydrotestosterone (DHT. Human normal bladder and BC biopsies and mouse bladder were examined quantitatively for thrombospondin-1 (TSP1 protein expression. Results Mice castrated at 24 weeks of age had decreased BC volumes at 32 weeks compared to intact mice (p = 0.0071 and castrated mice administered DHT (p = 0.0233; one-way ANOVA, JMP 6.0.3, SAS Institute, Inc.. Bladder cancer cell lines responded to DHT treatment with increased proliferation, regardless of androgen receptor expression levels. TSP1, an anti-angiogenic factor whose expression is inhibited by androgens, had decreased expression in bladders of UPII-SV40T mice compared to wild-type. Castration increased TSP1 levels in UPII-SV40T mice compared to intact mice. TSP1 protein expression was higher in 8 of 10 human bladder biopsies of normal versus malignant tissue from the same patients. Conclusion

  2. A great option for elderly patients with locally invasive bladder cancer, BOAI-CDDP-radiation (OMC regimen).

    Science.gov (United States)

    Azuma, Haruhito; Inamoto, Teruo; Takahara, Kiyoshi; Nomi, Hayahito; Hirano, Hajime; Uehara, Hiroshi; Komura, Kazumasa; Minami, Koichiro; Kouno, Junko; Kotake, Yatsugu; Abe, Hirokazu; Takagi, Shizuko; Ibuki, Naokazu; Yamamoto, Kazuhiro; Narumi, Yoshihumi; Kiyama, Satoshi

    2013-10-01

    We have developed a novel bladder preservation therapy, balloon-occluded arterial infusion (BOAI) of cisplatin/gemcitabine, concomitantly with hemodialysis, along with concurrent irradiation [the so-called 'OMC (Osaka Medical College) regimen']. The OMC regimen delivers an extremely high concentration of anticancer agent to the site of a tumor without systemic adverse effects, since more than 95% of free Pt was efficiently eliminated by hemodialysis, which enables short hospital stay. In this study, we investigated the efficiency of OMC regimen in patients aged over 70 years with muscle-invasive bladder cancer without metastasis. A total of 134 such patients were assigned to receive either the OMC regimen (n=89) or cystectomy (n=45). OMC regimen patients who failed to achieve CR underwent cystectomy, or secondary BOAI with gemcitabine (1,600 mg). The OMC regimen, which delivers an extremely high concentration of anticancer agent to the tumor site without systemic adverse effects, yielded CR in >91% (81/89) of patients. More than 96% (78/81) of the CR patients survived without recurrence with intact bladder after a mean follow-up of 164 (range 16-818) weeks. The 5- and 10-year bladder intact survival rates were 87.2 and 69.8%, and overall survival rates were 88.4 and 70.7% (vs. 59.9 and 33.3% for cystectomy, p=0.0002), respectively, although the median age in the OMC regimen group was significantly greater than in the cystectomy group (median, range = 77, 70-98 vs. 74, 70-89; p=0.0003). No patients suffered grade II or more severe toxicities; the oldest patient, aged 91 years, successfully completed this therapy. In conclusion, the OMC regimen is a useful bladder preservation strategy for elderly patients with locally invasive bladder cancer, not only in those for whom cystectomy is indicated, but also in patients whose condition is not amenable to curative treatment and for whom palliation would otherwise seem the only option.

  3. Development of oxybutynin chloride topical gel for overactive bladder

    Directory of Open Access Journals (Sweden)

    Lucente VR

    2011-04-01

    Full Text Available Vincent R Lucente1, David R Staskin2, Elise De31Institute of Female Pelvic Medicine and Reconstructive Surgery, Allentown, PA, USA; 2Division of Urology, St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, MA, USA; 3Urological Institute of Northeastern New York, Albany, NY, USAAbstract: Overactive bladder (OAB is an age-related syndrome often associated with urinary incontinence. Symptoms of OAB, such as urgency, frequency, and nocturia, can be treated effectively with inhibitors of muscarinic acetylcholine receptors. Antimuscarinic agents promote relaxation of the detrusor muscle and may modulate afferent neuronal signals involved in the regulation of the micturition reflex. Despite the availability of an increasing number of oral antimuscarinic agents, treatment persistence among patients with OAB generally appears to be low. This may be attributed, at least in part, to the common occurrence of anticholinergic adverse effects, such as dry mouth, constipation, and dizziness. Oxybutynin is a well-established antimuscarinic agent that is available in a variety of formulations. Transdermal formulations have been developed to avoid the first-pass hepatic and gastrointestinal drug metabolism responsible for the anticholinergic adverse effects often observed with oral delivery of oxybutynin. Oxybutynin chloride topical gel (OTG is a formulation of oxybutynin that was approved by the US Food and Drug Administration in January 2009. OTG was the result of a systematic evidence-based effort to develop a formulation that preserves the efficacy of oral oxybutynin formulations while eliminating most of their anticholinergic adverse effects. Additional emphasis was put on creating a transdermal formulation with minimal potential for application-site skin reactions. The formulation and pharmacokinetic properties of OTG are reviewed in the context of recently published efficacy and tolerability data from a large multicenter, placebo

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  5. Kaempferol Promotes Apoptosis in Human Bladder Cancer Cells by Inducing the Tumor Suppressor, PTEN

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    Liqun Zhou

    2013-10-01

    Full Text Available Kaempferol (Kae, a natural flavonoid, is widely distributed in fruits and vegetables. Previous studies have identified Kae as a possible cancer preventive and therapeutic agent. We found Kae to exhibit potent antiproliferation and anti-migration effects in human bladder cancer EJ cells. Kaempferol robustly induced apoptosis in EJ cells in a dose-dependent manner, as evidenced by increased cleavage of caspase-3. Furthermore, we found Kae-induced apoptosis in EJ cells to be associated with phosphatase and the tensin homolog deleted on the chromosome 10 (PTEN/PI3K/Akt pathway. Kae significantly increased PTEN and decreased Akt phosphorylation. Kae-induced apoptosis was partially attenuated in PTEN-knockdown cells. Our findings indicate that Kae could be an alternative medicine for bladder cancer, based on a PTEN activation mechanism.

  6. An Efficient Light-Inducible P53 Expression System for Inhibiting Proliferation of Bladder Cancer Cell

    Science.gov (United States)

    Lin, Fan; Dong, Liang; Wang, Weiming; Liu, Yuchen; Huang, Weiren; Cai, Zhiming

    2016-01-01

    Optogenetic gene expression systems enable spatial-temporal modulation of gene transcription and cell behavior. Although applications in biomedicine are emerging, the utility of optogenetic gene switches remains elusive in cancer research due to the relative low gene activation efficiency. Here, we present an optimized CRISPR-Cas9-based light-inducible gene expression device that controls gene transcription in a dose-dependent manner. To prove the potential utility of this device, P53 was tested as a functional target in the bladder cancer cell models. It was illustrated that the light-induced P53 inhibited proliferation of 5637 and UMUC-3 cell effectively. The “light-on” gene expression system may demonstrate a novel therapeutic strategy for bladder cancer intervention. PMID:27766041

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

    DEFF Research Database (Denmark)

    van Tilborg, Angela A G; Kompier, Lucie C; Lurkin, Irene

    2012-01-01

    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...... 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.......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...

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

    Directory of Open Access Journals (Sweden)

    Tao Zhang

    2013-12-01

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

  9. Curcumin Promotes KLF5 Proteasome Degradation through Downregulating YAP/TAZ in Bladder Cancer Cells

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    Yang Gao

    2014-08-01

    Full Text Available KLF5 (Krüppel-like factor 5 plays critical roles in normal and cancer cell proliferation through modulating cell cycle progression. In this study, we demonstrated that curcumin targeted KLF5 by promoting its proteasome degradation, but not by inhibiting its transcription in bladder cancer cells. We also demonstrated that lentivirus-based knockdown of KLF5 inhibited cancer cell growth, while over-expression of a Flag-tagged KLF5 could partially reverse the effects of curcumin on cell growth and cyclin D1 expression. Furthermore, we found that curcumin could down-regulate the expression of Hippo pathway effectors, YAP and TAZ, which have been reported to protect KLF5 protein from degradation. Indeed, knockdown of YAP by small interfering RNA caused the attenuation of KLF5 protein, but not KLF5 mRNA, which was reversed by co-incubation with proteasome inhibitor. A xenograft assay in nude mice finally proved the potent inhibitory effects of curcumin on tumor growth and the pro-proliferative YAP/TAZ/KLF5/cyclin D1 axis. Thus, our data indicates that curcumin promotes KLF5 proteasome-dependent degradation through targeting YAP/TAZ in bladder cancer cells and also suggests the therapeutic potential of curcumin in the treatment of bladder cancer.

  10. Clinical Experiences of Korean Medicine Treatment against Urinary Bladder Cancer in General Practice

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    Taeyeol Park

    2016-01-01

    Full Text Available Urinary bladder cancer (UBC is one of the most common cancers, with 1 out of every 26 men and 1 out of every 80 women worldwide developing the disease during their lifetime. Moreover, it is a disease that predominantly affects the elderly and is becoming a major health problem as the elderly population continues to rapidly increase. In spite of the rapid development of medical science, the 5-year survival rate has remained around 75% since the 1990s, and the FDA has approved no new drugs for UBC over the last 10 years. In addition, most patients experience frequent recurrence and poor quality of life after diagnosis. Therefore, in order to solve unmet needs by alternative methods, we present our clinical cases of UBC where we observed outstanding results including regression and recurrence prevention exclusively through Traditional Korean Medicine such as (1 herbal therapy, (2 acupuncture, (3 pharmacopuncture and needle-embedding therapy, (4 moxibustion, and (5 cupping therapy. From our experience, it appears that multimodal strategies for synergistic efficiency are more effective than single Korean Medicine treatment. We hope this will encourage investigation of the efficacy of Korean Medicine treatment in clinical trials for UBC patients.

  11. Classification of Laser Induced Fluorescence Spectra from Normal and Malignant bladder tissues using Learning Vector Quantization Neural Network in Bladder Cancer Diagnosis

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; Mascarenhas, Kim Komal; Patil, Choudhary

    2008-01-01

    the classification accuracy of LVQ with other classifiers (eg. SVM and Multi Layer Perceptron) for the same data set. Good agreement has been obtained between LVQ based classification of spectroscopy data and histopathology results which demonstrate the use of LVQ classifier in bladder cancer diagnosis....

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

    Science.gov (United States)

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

    2010-11-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  14. Intraoperative photodynamic therapy of bladder cancer with alasens (results of multicenter trial

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    E. V. Filonenko

    2014-01-01

    Full Text Available The results of multicenter prospective trial for efficacy of combined modality treatment: transurethral resection (TUR + photodynamic therapy (PDT with alasens for bladder cancer are represented in the article. Trials were organized by Research Institute of Organic Intermediates and Dyes and conducted according to clinical protocol approved by Ministry of Health of Russia, at the sites of leading Russian cancer clinical centers. The trial included 45 subjects with verified diagnosis of non-muscle-invasive bladder cancer. Patients underwent TUR of bladder with simultaneous PDT as anti-relapse treatment. Alasens was administered to patients as intravesicular instillation of 3% solution in volume of 50 ml with 1.5–2h exposure (prior to TUR. TUR was performed after instillation. PDT session was conducted immediately after the completion of TUR on a single occasion by means of combined local irradiation on tumor bed with diffuse irradiation on whole urinary bladder mucosa (light dose of local irradiation – 100 J/cm2, diffuse irradiation – 20 J/cm2. Good tolerance of the treatment was noticed, there were no complications. Among 45 patients included in the trial, 35 (78% completed 12 month protocol follow-up without relapse. The recurrence of bladder tumor was registered in 10 (22% cases 6–12 months after TUR+PDT including 3 patients with recurrence 6 months after treatment, 3–9 months and 4–12 months. These patients underwent repeated TUR, whereafter their follow-up in the settings of the clinical trial was disposed. Thus, PDT with alasens after TUR allowed to decrease the recurrence rate of non-muscle-invasive bladder cancer for 1st year after treatment to 22% versus 40–80% for TUR as monotherapy according to literature data. The obtained results were comparable by efficiency with TUR combined with methods of adjuvant treatment for bladder tumors (the recurrence rates for 1-year follow-up after TUR+chemotherapy – 36–44%, after TUR

  15. Study of the prediction system for clinical response to M-VAC neoadjuvant chemotherapy for bladder cancer.

    Science.gov (United States)

    Takata, R; Obara, W; Fujioka, T

    2010-01-01

    Neoadjuvant chemotherapy for invasive bladder cancer, involving a regimen of M-VAC, can manage micrometastasis and improve the prognosis. However, some patients suffer from severe adverse drug reactions without any effect, and no method yet exists for predicting the response of an individual patient to chemotherapy. Our purpose in this study is to establish a method for predicting the response to the M-VAC therapy. We analyzed gene-expression profiles of biopsy materials from 40 invasive bladder cancers using a cDNA microarray consisting of 27 648 genes, after populations of cancer cells had been purified by laser-microbeam microdissection. We identified 14 predictive genes that were expressed differently between nine responder and nine non-responder tumors and devised a prediction-scoring system that clearly separated the responder group from the non-responder group. This system accurately predicted the clinical response for 19 of the 22 additional test cases. The group of patients with positive predictive scores had significantly longer survival times than that with negative scores. As real-time RT-PCR data were highly concordant with the cDNA microarray data for those 14 genes, we developed a quantitative RT-PCR-based prediction system that could be feasible for routine clinical use. Taken together, our results suggest that the sensitivity of an invasive bladder cancer to the M-VAC neoadjuvant chemotherapy can be predicted by expression patterns in this set of genes, a step toward achievement of "personalized therapy" for treatment of this disease.

  16. СHANGES IN PARAMETERS OF LUMINOL-DEPENDENT AND LUCIGENIN-DEPENDENT CHEMILUMINESCENCE OF PERIPHERAL BLOOD NEUTROPHILS IN PATIENTS WITH BLADDER CANCER IN THE DISEASE DYNAMICS

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    L. M. Kurtasova

    2015-01-01

    Full Text Available The study deals with parameters of luminol-dependent and lucigenin-dependent chemiluminescence (CL of peripheral blood neutrophils from patients with bladder cancer (BC prior to surgical treatment. We examined sixty patients (45 to 55 years old with advanced bladder cancer (TNM prior to the operation, and forty-six patients at 10 days after surgical treatment. A control group consisted of 56 healthy donors. Luminol-dependent and lucigenin-dependent chemiluminescence of blood neutrophils was assessed according to De Sole et al. (1983. Chemiluminescence assays of peripheral blood neutrophils from the patients with bladder cancer revealed changes in production of reactive oxygen species (ROS, both for initial stage of oxidation reaction, and total level of active oxygen radicals. We have found disturbed values of primary-to-secondary ROS ratio in the cells. In the patients with bladder cancer, some changes in oxidative metabolism of the blood neutrophils have been registered. These alterations may play an important role in promotion of potential effector cell functions, thus, probably, affecting the whole-scale development of a cytopathic effect exerted by neutrophilic granulocytes. 

  17. EDTA-induced pseudothrombocytopenia in association with bladder cancer.

    Science.gov (United States)

    Sahin, Cem; Kırlı, Ismail; Sozen, Hamdi; Canbek, Tugba Dibektas

    2014-06-20

    Pseudothrombocytopenia is the detection of low platelet counts by an autoanalyser despite lack of shortage in platelets. EDTA-induced pseudothrombocytopenia, the most frequently seen form in clinical practice, occurs mainly due to reaction of antiplatelet antibodies. Pseudothrombocytopenia is not only seen in healthy individuals but it is also reported in association with autoimmune, cardiovascular and liver parenchyma diseases and malignancy. We aimed to review approaches to pseudothrombocytopenia by presenting a case in which EDTA-dependent thrombocytopenia in association with bladder tumour was detected during examination for haematuria.

  18. Comparison of seven screening methods in the diagnosis of bladder cancer

    Institute of Scientific and Technical Information of China (English)

    SUN Yi; HE Da-lin; MA Qiang; WAN Xing-yang; ZHU Guo-dong; LI Lei; LUO Yong; HE Hui; YANG Lin

    2006-01-01

    Background We compared the validity (evaluated by sensitivity and specificity), reliability (evaluated by reproducibility) and yield (evaluated by predictive value, examining complexity and cost) of individual and combined tests for bladder tumour antigen stat (BTAstat), nuclear matrix protein 22 (NMP22), hyaluronic acid (HA), survivin, CD44v6, vascular endothelial growth factor (VEGF), and voided urine cytology (VUC) in detecting bladder cancer. And at the same time we evaluated the clinical value of these seven detecting methods in the diagnosis of bladder cancer.Methods The six markers and VUC were detected in the urine of cancer group (151 patients with bladder cancer) and two control groups (50 patients with benign urological diseases and 50 healthy controls). The sensitivity, specificity, predictive value, reproducibility, examining complexity and checking cost of each marker and combined markers were calculated.Results There was a significant difference between bladder cancer group and the two control groups. The sensitivity, specificity and positive predictive value were as follows: VUC (36.4%, 100.0%, 100%), BTAstat (76.8%, 87.0%, 89.9%), NMP22 (77.5%, 81.0%, 86.0%), HA (82.8%, 83.0%, 88.0%), survivin (70.2%, 85.0%,87.6%), CD44v6 (50.3%, 79.0%, 78.4%), and VEGF (68.2%, 93.0%, 93.6%). The highest sensitivities were 91.4% for NMP22+BTAstat and HA+NMP22, whereas the combined marker with the lowest sensitivity (62.3%)was VUC+CD44v6. The highest specificity was 93.0% for the combined use of VUC+VEGF and HA+CD44v6 had the lowest specificity (73.0%). The most convenient examining method was the detection for BTAstat, the lowest cost was the detection for HA, and the best reproducibility were the detection for BTAstat and VUC.Conclusions All the markers have obvious clinical value in diagnosis of bladder cancer. The use of BTAstat+HA or NMP22+BTAstat are better examining methods in terms of validity, reliability, and yield.

  19. Molecular Detection of Bladder Cancer by Fluorescence Microsatellite Analysis and an Automated Genetic Analyzing System

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    Sarel Halachmi

    2007-01-01

    Full Text Available To investigate the ability of an automated fluorescent analyzing system to detect microsatellite alterations, in patients with bladder cancer. We investigated 11 with pathology proven bladder Transitional Cell Carcinoma (TCC for microsatellite alterations in blood, urine, and tumor biopsies. DNA was prepared by standard methods from blood, urine and resected tumor specimens, and was used for microsatellite analysis. After the primers were fluorescent labeled, amplification of the DNA was performed with PCR. The PCR products were placed into the automated genetic analyser (ABI Prism 310, Perkin Elmer, USA and were subjected to fluorescent scanning with argon ion laser beams. The fluorescent signal intensity measured by the genetic analyzer measured the product size in terms of base pairs. We found loss of heterozygocity (LOH or microsatellite alterations (a loss or gain of nucleotides, which alter the original normal locus size in all the patients by using fluorescent microsatellite analysis and an automated analyzing system. In each case the genetic changes found in urine samples were identical to those found in the resected tumor sample. The studies demonstrated the ability to detect bladder tumor non-invasively by fluorescent microsatellite analysis of urine samples. Our study supports the worldwide trend for the search of non-invasive methods to detect bladder cancer. We have overcome major obstacles that prevented the clinical use of an experimental system. With our new tested system microsatellite analysis can be done cheaper, faster, easier and with higher scientific accuracy.

  20. Chemopreventive effect of omega-3 polyunsaturated fatty acids and atorvastatin in rats with bladder cancer.

    Science.gov (United States)

    El-Ashmawy, Nahla E; Khedr, Eman G; El-Bahrawy, Hoda A; Al-Tantawy, Samar M

    2017-02-01

    Bladder cancer remains a huge concern for the medical community because of its incidence and prevalence rates, as well as high percentage of recurrence and progression. Omega-3 polyunsaturated fatty acids and atorvastatin proved anti-inflammatory effects through peroxisome proliferator-activated receptor gamma mechanism. However, their chemopreventive effect still remained to be examined and clarified. In this study, bladder cancer was induced in rats by the chemical carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. Omega-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid: 2:3 w/w; 1200 mg/kg) and/or atorvastatin (6 mg/kg) were given orally daily to rats for eight consecutive weeks concomitantly with N-butyl-N-(4-hydroxybutyl)nitrosamine and continued for further 4 weeks after cessation of N-butyl-N-(4-hydroxybutyl)nitrosamine administration. The histopathological examination of rat bladder revealed the presence of tumors and the absence of apoptotic bodies in sections from N-butyl-N-(4-hydroxybutyl)nitrosamine group, while tumors were absent and apoptotic bodies were clearly observed in sections from rat groups treated with omega-3 polyunsaturated fatty acids, atorvastatin, or both drugs. The study of the molecular mechanisms illustrated downregulation of COX-2 and P53 (mutant) genes and suppression of transforming growth factor beta-1 and the lipid peroxidation product malondialdehyde in serum of rats of the three treated groups. This chemopreventive effect was confirmed by and associated with lower level of bladder tumor antigen in urine. However, the combined treatment with both drugs exhibited the major protective effect and nearly corrected the dyslipidemia that has been induced by N-butyl-N-(4-hydroxybutyl)nitrosamine. Collectively, omega-3 polyunsaturated fatty acids and atorvastatin, besides having anti-inflammatory properties, proved a chemopreventive effect against bladder cancer, which nominates them to be used as

  1. Responses to hexyl 5-aminolevulinate-induced photodynamic treatment in rat bladder cancer model

    Science.gov (United States)

    Arum, Carl-Jørgen; Gederas, Odrun; Larsen, Eivind; Randeberg, Lise; Zhao, Chun-Mei

    2010-02-01

    OBJECTIVES: In this study, we evaluated histologically the effects of hexyl 5-aminolevulinateinduced photodynamic treatment in the AY-27 tumor cell induced rat bladder cancer model. MATERIAL & METHODS: The animals (fischer-344 female rats) were divided into 2 groups, half of which were orthotopically implanted with 400,000 syngeniec AY-27 urothelia1 rat bladder cancer cells and half sham implanted. 14 days post implantation 6 rats from each group were treated with hexyl 5-aminolevulinate-induced photodynamic treatment (8mM HAL and light fluence of 20 J/cm2). Additional groups of animals were only given HAL instillation, only light treatment, or no treatment. All animals were sacrificed 7 days after the PDT/only HAL/only light or no treatment. Each bladder was removed, embedded in paraffin and stained with hematoxylin, eosin, and saferin for histological evaluation at high magnification for features of tissue damage by a pathologist blinded to the sample source. RESULTS: In all animals that were AY-27 implanted and not given complete PDT treatment, viable tumors were found in the bladder mucosa and wall. In the animals treated with complete HAL-PDT only 3 of 6 animals had viable tumor. In the 3 animals with viable tumor it was significantly reduced in volume compared to the untreated animals. It was also noted that in the PDT treated animals there was a significantly increased inflammatory response (lymphocytic and mononuclear cell infiltration) in the peri-tumor area compared to implanted animals without complete HAL-PDT. CONCLUSION: Our results suggest that hexyl 5-aminolevulinate-induced photodynamic treatment in a rat bladder cancer model involves both direct effects on cell death (necrosis and apoptosis) and indirect effects to evoke the host immune-response, together contributing to tumor eradication.

  2. Differential Proteomic Analysis of Nuclear Matrix in Muscle-Invasive Bladder Cancer: Potential to Improve Diagnosis and Prognosis

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    Paola Barboro

    2008-01-01

    Full Text Available Introduction: Although several molecular markers for bladder cancer have been identified, at present little information on prognostic biomarkers is available in the literature. Prognostication of this tumor is largely based on clinicopathological characteristics. Our aim was to identify nuclear matrix (NM proteins that might serve to better characterize the phenotype of the invasive bladder cancer and to investigate their diagnostic and prognostic roles.

  3. Effects of neoadjuvant chemotherapy on pathological parameters and survival in patients undergoing radical cystectomy for muscle-invasive bladder cancer

    OpenAIRE

    ÇAĞLAYAN, Alper; Akbulut, Ziya; Atmaca, Ali Fuat; Altinova,Serkan; KILIÇ, Metin; Balbay, Mevlana Derya

    2012-01-01

    Aim: To evaluate the effect of neoadjuvant chemotherapy on tumor pathology and patient survival in patients with muscle-invasive bladder cancer undergoing radical cystectomy. Neoadjuvant chemotherapy is believed to prevent micrometastasis and provide pathological downstaging. Materials and methods: Between June 2004 and March 2009, 74 patients with muscle-invasive bladder cancer were treated with radical cystectomy. Patients fit to receive chemotherapy were administered systemic chemotherapy...

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

    Science.gov (United States)

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

    2002-03-10

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

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

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    Haifeng Zhang

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

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

    Science.gov (United States)

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

    2009-11-01

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

  7. Patterns of recurrence in bladder cancer treated by irradiation and/or cystectomy

    Energy Technology Data Exchange (ETDEWEB)

    Batata, M.A.; Whitmore, W.F. Jr.; Chu, F.C.H.; Hilaris, B.S.; Unal, A.; Chung, S.

    1980-02-01

    Between 1949 and 1971, 451 patients with bladder cancer were treated by radiation therapy and/or radical cystectomy at the Memorial Sloan-Kettering Cancer Center. Radical cystectomy alone was the treatment for 137 patients in Group 1. In Group 2, 109 patients received radiation therapy to an average tumor dose of 6000 rad in 6 weeks +- 1 year before radical cystectomy for persistent, recurrent or new lesions. Planned preoperative irradiation consisted of either 4000 rad in 4 weeks for 119 patients in Group 3, or 2000 rad in 1 week for 86 patients in Group 4, +- 6 weeks and 2 days, respectively, before radical cystectomy. The determinate over-all distant and/or local recurrence rate was 49% for Group 1 and 37 to 45% for Groups 2 to 4. Local recurrence alone occurred in 28% of Group 1 patients and 14 to 16% of those in Groups 2 to 4. Distant metastases developed in 21% of Group 1 patients and 22 to 28% of Group 2 to 4 patients. A reduced incidence of pelvic recurrence was associated with radiation-induced stage reduction for Group 2 to 4 clinically high and low stage tumors, especially when the histologic grade was high. Similar frequencies of extrapelvic metastases in the four groups were maintained in clinically low and high stage tumors of low or high histological grade.

  8. Bladder Cancer and Urothelial Impairment: The Role of TRPV1 as Potential Drug Target

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    Francesco Mistretta

    2014-01-01

    Full Text Available Urothelium, in addition to its primary function of barrier, is now understood to act as a complex system of cell communication that exhibits specialized sensory properties in the regulation of physiological or pathological stimuli. Furthermore, it has been hypothesized that bladder inflammation and neoplastic cell growth, the two most representative pathological conditions of the lower urinary tract, may arise from a primary defective urothelial lining. Transient receptor potential vanilloid channel 1 (TRPV1, a receptor widely distributed in lower urinary tract structures and involved in the physiological micturition reflex, was described to have a pathophysiological role in inflammatory conditions and in the genesis and development of urothelial cancer. In our opinion new compounds, such as curcumin, the major component of turmeric Curcuma longa, reported to potentiate the effects of the chemotherapeutic agents used in the management of recurrent urothelial cancer in vitro and also identified as one of several compounds to own the vanillyl structure required to work like a TRPV1 agonist, could be thought as complementary in the clinical management of both the recurrences and the inflammatory effects caused by the endoscopic resection or intravesical chemotherapy administration or could be combined with adjuvant agents to potentiate their antitumoral effect.

  9. HIF-1α/MDR1 pathway confers chemoresistance to cisplatin in bladder cancer.

    Science.gov (United States)

    Sun, Yi; Guan, Zhenfeng; Liang, Liang; Cheng, Yongyi; Zhou, Jiancheng; Li, Jing; Xu, Yonggang

    2016-03-01

    Bladder cancer (BCa) is the 9th most common malignant tumor and the 13th leading cause of death due to cancer. The development of surgery and target drugs bring new challenges for the traditional concept for BCa therapy, and chemotherapy is still the final option for many BCa patients, and cisplatin-containing regimen the most effective one. However, the ubiquitous application of cisplatin-containing regimen in BCa results in the cisplatin-resistance, in addition, the cisplatin‑resistant BCa manifests enhanced malignant behavior, the mechanism of which is unclear. In the present study, we used BCa cell lines to to clarify this point. BCa cell lines T24/J82 were pretreated with cisplatin >3 months to construct stable cisplatin-resistant cell lines (tagged T24(Cis-R) and J82(Cis-R)), which manifested as enhanced capacity of proliferation and malignant behavior in vivo and in vitro, accompanied by cisplatin, and even doxorubicin resistance. The following mechanism dissection revealed that prolonged treatment time of T24/J82 cells led to elevated expression of HIF-1α, which targeted the increased expression of MDR1 on the one hand, and contributed to BCa cell proliferation, migration/invasion on the other hand. Finally, IHC staining of human BCa tissue supported our conclusion that the expression of HIF-1α and MDR1 was higher in chemoresistant tissue vs. chemosensitive tissue. Our results provided a new view of HIF-1α in chemotherapy.

  10. A rare bladder cancer - small cell carcinoma: review and update

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    Ismaili Nabil

    2011-11-01

    Full Text Available Abstract Small cell carcinoma of the bladder (SCCB is rare, highly aggressive and diagnosed mainly at advanced stages. Hematuria is the main symptom of this malignancy. The origin of the disease is unknown; however the multipotent stem cell theory applies best to this case. Histology and immunohistochemistry shows a tumour which is indistinguishable from small cell lung carcinoma (SCLC. Coexistence of SCCB with other types of carcinoma is common. The staging system used is the TNM-staging of bladder transitional cell carcinoma. The treatment is extrapolated from that of SCLC. However, many patients with SCCB undergo radical resection which is rarely performed in SCLC. Patients with surgically resectable disease ( or = cT4bN+M+ should be managed with palliative chemotherapy based on neuroendocrine type regimens comprising a platinum drug (cisplatin in fit patients. The prognosis of the disease is poor mainly in the case of pure small cell carcinoma. Other research programs are needed to improve the outcome of SCCB.

  11. Targeted therapies in bladder cancer: an overview of in vivo research.

    Science.gov (United States)

    van Kessel, Kim E M; Zuiverloon, Tahlita C M; Alberts, Arnout R; Boormans, Joost L; Zwarthoff, Ellen C

    2015-12-01

    Survival of patients with muscle-invasive bladder cancer is poor and new therapies are needed. Currently, none of the targeted agents that are approved for cancer therapy have been approved for the treatment of bladder cancer and the few clinical trials that have been performed had limited success, often owing to a lack of efficacy and toxic effects. However, many other novel targeted agents have been investigated in animal models of bladder cancer. EGFR, FGFR-3, VEGF, mTOR, STAT3, the androgen receptor and CD24 are molecular targets that could be efficiently inhibited, resulting in reduced tumour growth, and that have been investigated in multiple independent studies. Several other targets, for example COX-2, IL-12, Bcl-xL, livin and choline kinase α, have also been observed to inhibit tumour growth, but these findings have not been replicated to date. Limitations of several studies include the use of cell lines with mutations downstream of the target, providing resistance to the tested therapy. Furthermore, certain technologies, such as interfering RNAs, although effective in vitro, are not yet ready for clinical applications. Further preclinical research is needed to discover and evaluate other possible targets, but several validated targets are now available to be studied in clinical trials.

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

    Science.gov (United States)

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

    2014-03-01

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

  13. A comparative study of two preoperative radiation regimens with cystectomy for bladder cancer.

    Science.gov (United States)

    Whitmore, W F; Batata, M A; Hilaris, B S; Reddy, G N; Unal, A; Ghoneim, M A; Grabstald, H; Chu, F

    1977-09-01

    This report surveys the results of two programs of preoperative irradiation with radical cystectomy for bladder cancer in 205 patients. Irradiating the true pelvis to 4000 rads in 4 weeks with radical cystectomy after 6 weeks was implemented in 119 patients (Group 1) from 1959 to 1965; 2000 rads given in 1 week to the true pelvis and radical cystectomy within the following week was implemented in 86 patients (Group 2) from 1966 to 1970. Determinate survival without evidence of recurrence at 5 years was 43% in Group 1 and 42% in Group 2. Mortality with recurrence of bladder cancer in 5 or more years was 44% in group 1 and 42% in group 2. Pelvic complications occurred in 13% of group 1 and 9% of group 2.

  14. Mycobacterium bovis Bacillus Calmette-Guérin-Induced Macrophage Cytotoxicity against Bladder Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yi Luo

    2010-01-01

    Full Text Available Many details of the molecular and cellular mechanisms involved in Mycobacterium bovis bacillus Calmette-Guérin (BCG immunotherapy of bladder cancer have been discovered in the past decades. However, information on a potential role for macrophage cytotoxicity as an effector mechanism is limited. Macrophages play pivotal roles in the host innate immunity and serve as a first line of defense in mycobacterial infection. In addition to their function as professional antigen-presenting cells, the tumoricidal activity of macrophages has also been studied with considerable interest. Studies have shown that activated macrophages are potent in killing malignant cells of various tissue origins. This