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Sample records for bladder cancer 3

  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. Treatment Option Overview (Bladder Cancer)

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    ... 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 ...

  3. Stages of Bladder Cancer

    Science.gov (United States)

    ... red in color). Frequent urination. Pain during urination. Lower back pain. Tests that examine the urine and bladder are used to help detect (find) and diagnose bladder cancer. The following tests and ... left. Treatment given after surgery, to lower the risk that the cancer will come back, ...

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

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    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.

  5. 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.

  6. [Occupational hazards and bladder cancer].

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    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.

  7. Soluble vascular endothelial growth factor receptor-3 suppresses lymphangiogenesis and lymphatic metastasis in bladder cancer

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    Kim Wun-Jae

    2011-04-01

    Full Text Available Abstract Background Most bladder cancer patients experience lymphatic metastasis in the course of disease progression, yet the relationship between lymphangiogenesis and lymphatic metastasis is not well known. The aim of this study is to elucidate underlying mechanisms of how expanded lymphatic vessels and tumor microenvironment interacts each other and to find effective therapeutic options to inhibit lymphatic metastasis. Results The orthotopic urinary bladder cancer (OUBC model was generated by intravesical injection of MBT-2 cell lines. We investigated the angiogenesis, lymphangiogenesis, and CD11b+/CD68+ tumor-associated macrophages (TAM by using immunofluorescence staining. OUBC displayed a profound lymphangiogenesis and massive infiltration of TAM in primary tumor and lymphatic metastasis in lymph nodes. TAM flocked near lymphatic vessels and express higher levels of VEGF-C/D than CD11b- cells. Because VEGFR-3 was highly expressed in lymphatic vascular endothelial cells, TAM could assist lymphangiogenesis by paracrine manner in bladder tumor. VEGFR-3 expressing adenovirus was administered to block VEGF-C/D signaling pathway and clodronate liposome was used to deplete TAM. The blockade of VEGF-C/D with soluble VEGF receptor-3 markedly inhibited lymphangiogenesis and lymphatic metastasis in OUBC. In addition, the depletion of TAM with clodronate liposome exerted similar effects on OUBC. Conclusion VEGF-C/D are the main factors of lymphangiogenesis and lymphatic metastasis in bladder cancer. Moreover, TAM plays an important role in these processes by producing VEGF-C/D. The inhibition of lymphangiogenesis could provide another therapeutic target to inhibit lymphatic metastasis and recurrence in patients with invasive bladder cancer.

  8. Postoperative radiotherapy combined with intravesical chemotherapy for T2/T3 bladder cancer

    International Nuclear Information System (INIS)

    Objective: To compare the result of T2/T3 transitional cell carcinoma (TCC) of the urinary bladder after segmental cystectomy, treated by postoperative radiation plus intravesical chemotherapy and postoperative intravesical chemotherapy alone. Methods: From 1985 to Dec. 1995 patients with T2/T3 TCC bladder cancer who had been treated by segmental cystectomy were eligible for this retrospective analysis. Fifty-eight patients received postoperative radiotherapy plus intravesical chemotherapy (RT + IVC) and 35 patients were given postoperative intravesical chemotherapy (IVC) with thio-TEPA or Calmette-Gue' rin bacilli (BCG). For radiation, 8 or 18 MV X-ray was given with total dose of 50-60 Gy. Vesicoclysis was performed on 50-60 mg thio-TEPA twice per week and 0.5 mg BCG per week. Results: The 3-year local control rates of RT + IVC and IVC groups were 68.6% and 48.2% showing a difference statistically significant (x2 = 4.08, P = 0.044). The 3- and 5-year survival rates of RT + IVC and IVC groups were 70.7%, 49.5% and 59.9%, 35.7%, showing no significant difference (x2 = 1.77, P = 0.184). Among the 5 year survivors of the RT + IVC patients, 78.6% had their bladder preserved. Though untoward radiation reactions were severer, they were tolerated well. Conclusions: Combined radiation therapy plus intravesical chemotherapy is indicated for T2/T3 bladder cancer after segmental cystectomy. Multimodality therapy is more favored to improve both the local control and the possibility of preserving the bladder

  9. Treatment Options by Stage (Bladder Cancer)

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    ... 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 ...

  10. Association Study of Polymorphism in CYP3A5 Gene with Bladder Cancer

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    m bakhtiari tajar

    2015-09-01

    Full Text Available Aims and objectives: The environmental procarcinogen hypothesis of tumour pathogenesis proposes that many carcinogens require metabolic activation by drug metabolizing enzymes to form the proximate carcinogen. CYP3A enzyme catalyzes the conversion of numerous numbers of xenobiotics including carcinogens and drugs and it is involved in metabolic pathways of activation of procarcinogens and/or inactivation of carcinogens during the tumorigenic processes. CYP3A5 is expressed polymorphically in human liver, but consistently in lung, colon, and kidney. An allelic variant of A to G (A6986G transition causes CYP3A5*3 variant and this polymorphic expression confers low CYP3A5 protein expression as a result of improper mRNA splicing and reduced translation of a functional protein. The purpose of this study was to analysis the frequency of mutations in CYP3A5 gene and to determine the role of its polymorphisms in bladder cancer patients. Methods: For this purpose, PCR-RFLP analysis of the gene was on 113 bladder cancer patients and same number of age-matched controls admitted to Hashemi Nezhad Hospital was performed. Then the data was analyzed using the computer software SPSS for windows (version 19. Results: The incidence of CYP3A5*3 allele was more in patients and control group compared with the wild type (CYP3A5*1. It was 79.6% and 75.2% in patients and controls respectively which indicated that the mutant allele of CYP3A5*3 was more in the studied population with an OR of 1.837 (95% CI=0.975-3.460, P= 0.62. Also there was found that the frequency of both alleles were high in female compared with male. Conclusions: There was no significant association between the risk of bladder cancer for individuals carrying the CYP3A5*3 genotype.

  11. Metabolic phenotype of bladder cancer.

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    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

  12. Contemporary Management of Bladder Cancer

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    Bell, David; Fradet, Yves

    1991-01-01

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

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

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    Angeline S Andrew

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

  14. Immunotherapy for bladder cancer.

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

    2015-01-01

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

  15. Immunotherapy for bladder cancer

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    Fuge O

    2015-05-01

    Full Text Available Oliver Fuge,1 Nikhil Vasdev,1 Paula Allchorne,2 James SA Green2 1Department of Urology, Lister Hospital, Stevenage, UK; 2Department of Urology, Bartshealth NHS Trust, Whipps Cross Rd, London, UK Abstract: It is nearly 40 years since Bacillus Calmette–Guérin (BCG was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment. As a better understanding of its mechanism of action and the clinical response to it have evolved, some of the questions around optimal dosing and treatment protocols have been answered. However, its potential for toxicity and failure to produce the desired clinical effect in a significant cohort of patients presents an ongoing challenge to clinicians and researchers alike. This review summarizes the evidence behind the established mechanism of action of BCG in bladder cancer, highlighting the extensive array of immune molecules that have been implicated in its action. The clinical aspects of BCG are discussed, including its role in reducing recurrence and progression, the optimal treatment regime, toxicity and, in light of new evidence, whether or not there is a superior BCG strain. The problems of toxicity and non-responders to BCG have led to development of new techniques aimed at addressing these pitfalls. The progress made in the laboratory has led to the identification of novel targets for the development of new immunotherapies. This includes the potential augmentation of BCG with various immune factors through to techniques avoiding the use of BCG altogether; for example, using interferon-activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The potential role of gene, virus, or photodynamic therapy as an alternative to BCG is also reviewed. Recent interest in the immune check point system has led to the development of monoclonal antibodies against proteins involved in this pathway. Early findings suggest

  16. Emerging Immunotargets in Bladder Cancer.

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    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.

  17. Drugs Approved for Bladder Cancer

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    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.

  18. Optimal management of high-risk T1G3 bladder cancer: a decision analysis.

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    Girish S Kulkarni

    2007-09-01

    Full Text Available BACKGROUND: Controversy exists about the most appropriate treatment for high-risk superficial (stage T1; grade G3 bladder cancer. Immediate cystectomy offers the best chance for survival but may be associated with an impaired quality of life compared with conservative therapy. We estimated life expectancy (LE and quality-adjusted life expectancy (QALE for both of these treatments for men and women of different ages and comorbidity levels. METHODS AND FINDINGS: We evaluated two treatment strategies for high-risk, T1G3 bladder cancer using a decision-analytic Markov model: (1 Immediate cystectomy with neobladder creation versus (2 conservative management with intravesical bacillus Calmette-Guérin (BCG and delayed cystectomy in individuals with resistant or progressive disease. Probabilities and utilities were derived from published literature where available, and otherwise from expert opinion. Extensive sensitivity analyses were conducted to identify variables most likely to influence the decision. Structural sensitivity analyses modifying the base case definition and the triggers for cystectomy in the conservative therapy arm were also explored. Probabilistic sensitivity analysis was used to assess the joint uncertainty of all variables simultaneously and the uncertainty in the base case results. External validation of model outputs was performed by comparing model-predicted survival rates with independent published literature. The mean LE of a 60-y-old male was 14.3 y for immediate cystectomy and 13.6 y with conservative management. With the addition of utilities, the immediate cystectomy strategy yielded a mean QALE of 12.32 y and remained preferred over conservative therapy by 0.35 y. Worsening patient comorbidity diminished the benefit of early cystectomy but altered the LE-based preferred treatment only for patients over age 70 y and the QALE-based preferred treatment for patients over age 65 y. Sensitivity analyses revealed that patients

  19. Familial aggregation of bladder cancer

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    Ilić Milena

    2011-01-01

    Full Text Available Background. Except for smoking and certain occupational exposures, the etiology of bladder cancer is largely unknown. Several case reports have described familial aggregation of transitional cell carcinoma of the bladder. Although the majority of patients with bladder cancer do not have family history of transitional cell carcinoma of the urinary tract, the study of familial transitional cell carcinoma may lead to the knowledge on the pathogenesis of this disease. The purpose of this study was to describe three cases of urinary bladder cancer in a single three-member family, i.e. in two generations (mother and son and a family member related by marriage (the patient’s wife. Case report. Three cases of urinary bladder cancer occurred in a three-member family within the interval of 5 years. The following common characteristics were detected in our patients: old age (over 60, working as farmers for more than 50 years, negative personal medical history on relevant health disorders, place of birth - village, place of residence - village, the same water supply, similar nutrition, positive family history on urinary bladder cancer or other malignant tumors, the first sign of illness was macroscopic hematuria in all the patients and the same pathohistological type of cancer - carcinoma papillare transitiocellulare. Conclusion. The stated common characteristics in our cases indicate, above all, the impact of exposure to external surrounding factors on the occurrence of urinary bladder cancer.

  20. Detection Of Aneuploidy In Chromosomes 3,7,9 And 17 In Bladder Cancer Patients Using Urovysion Assay

    International Nuclear Information System (INIS)

    Background: Cystoscopy is considered up till now the gold standard as well as urine cytology for diagnosis and follow up of urinary bladder cancer patients. Cystoscopy is an invasive inconclusive technique while cytology have low sensitivity. Therefore search for a more sensitive, non-invasive highly reliable method is important. Aim of the study: To assess the diagnostic sensitivity and specificity of Urovysion to be used as a non-invasive tool for early detection of bladder cancer patients. Furthermore, to assess its relationship with histopathological stages and grades of the disease. Subjects and methods: This study was conducted on 30 patients with urinary bladder cancer( Group I) which were subdivided according to cancer stages and grades into subgroups and 15 diseased control patients (Group II). One urine sample was taken from each patient for Urovysion assay and another sample taken for urine cytology. Results: Urovysion showed higher positive results in (Group I) than urine cytology. In (Group II) the latter did not miss any negative case while urovysion showed only one false positive case. Moreover, Urovysion results revealed significant association with both bladder cancer histopathological stages and grades while urine cytology showed significant association with tumor grades only. Conclusion: Urovysion; both by itself and in combination with urine cytology; offers a sensitive, reliable and non invasive approach to bladder cancer diagnosis. Urovysion is associated with invasiveness of bladder cancer from stage Tis, T1 to T4 and from grades G1 to G3. Thus, urovysion assay can be used as an important diagnostic and prognostic indicator of this disease

  1. Steroid Receptor Coactivator-3 Regulates Glucose Metabolism in Bladder Cancer Cells through Coactivation of Hypoxia Inducible Factor 1α*

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

    2014-01-01

    Cancer cell proliferation is a metabolically demanding process, requiring high glycolysis, which is known as “Warburg effect,” to support anabolic growth. Steroid receptor coactivator-3 (SRC-3), a steroid receptor coactivator, is overexpressed and/or amplified in multiple cancer types, including non-steroid targeted cancers, such as urinary bladder cancer (UBC). However, whether SRC-3 regulates the metabolic reprogramming for cancer cell growth is unknown. Here, we reported that overexpression of SRC-3 accelerated UBC cell growth, accompanied by the increased expression of genes involved in glycolysis. Knockdown of SRC-3 reduced the UBC cell glycolytic rate under hypoxia, decreased tumor growth in nude mice, with reduction of proliferating cell nuclear antigen and lactate dehydrogenase expression levels. We further revealed that SRC-3 could interact with hypoxia inducible factor 1α (HIF1α), which is a key transcription factor required for glycolysis, and coactivate its transcriptional activity. SRC-3 was recruited to the promoters of HIF1α-target genes, such as glut1 and pgk1. The positive correlation of expression levels between SRC-3 and Glut1 proteins was demonstrated in human UBC patient samples. Inhibition of glycolysis through targeting HK2 or LDHA decelerated SRC-3 overexpression-induced cell growth. In summary, overexpression of SRC-3 promoted glycolysis in bladder cancer cells through HIF1α to facilitate tumorigenesis, which may be an intriguing drug target for bladder cancer therapy. PMID:24584933

  2. Transurethral microwave needle ablation for bladder cancer

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@To investigate the role of transurethral microwave needle ablation (TUMWNA) in the management of bladder cancer,TUMWNA was carried out in 24 patients with bladder cancer since 1989. From January 1989 to December 1997, 24 patients with bladder cancer were treated with TUMWNA. The 15 men and 9 women were 42 to 67 years old (mean, 58). There were 18 cases with a single tumor and 6 with multiple tumors (4 with 2 tumors, 1 with 3 and 1 with 4). Tumor diameter ranged from 0.3 to 2.5 cm. The lesions grew in different bladder regions: 13 tumors arose from the fundus, 3 tumors from the dome, 9 from the lateral wall, 5 from the anterior wall, 1 from the triangle region and 2 tumors were situated in the obturator nerve reflex sensitive region.

  3. Ct2 Bladder Cancer.

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    Soloway, Mark S

    2016-09-01

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

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

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

    2013-01-01

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

  5. Genetics Home Reference: bladder cancer

    Science.gov (United States)

    ... ND, Rubenstein JN, Eggener SE, Kozlowski JM. The p53 tumor suppressor gene and nuclear protein: basic science review and relevance in the management of bladder cancer. J Urol. 2003 Apr;169(4):1219-28. ...

  6. 1,25D3 enhances antitumor activity of gemcitabine and cisplatin in human bladder cancer models

    Science.gov (United States)

    Ma, Yingyu; Yu, Wei-Dong; Trump, Donald L.; Johnson, Candace S.

    2010-01-01

    Background 1,25 dihydroxyvitamin D3 (1,25D3) potentiates the cytotoxic effects of several common chemotherapeutic agents. The combination of gemcitabine and cisplatin (GC) is a current standard chemotherapy regimen for bladder cancer. We investigated whether 1,25D3 could enhance the antitumor activity of GC in bladder cancer model systems. Methods Human bladder cancer T24 and UMUC3 cells were pretreated with 1,25D3 followed by GC. Apoptosis were assessed by annexin V staining. Caspase activation was examined by immunoblot analysis and substrate-based caspase activity assay. The cytotoxic effects were examined using MTT and in vitro clonogenic assay. p73 protein levels were assessed by immunoblot analysis. Knockdown of p73 was achieved by siRNA. The in vivo antitumor activity was assessed by in vivo excision clonogenic assay and tumor regrowth delay in the T24 xenograft model. Results 1,25D3 pretreatment enhanced GC-induced apoptosis and the activities of caspases- 8, 9 and 3 in T24 and UMUC3 cells. 1,25D3 synergistically reduced GC-suppressed surviving fraction in T24 cells. 1,25D3, gemcitabine, or cisplatin induced p73 accumulation, which was enhanced by GC or 1,25D3 and GC. p73 expression was lower in human primary bladder tumor tissue compared with adjacent normal tissue. Knockdown of p73 increased clonogenic capacity of T24 cells treated with 1,25D3, GC or 1,25D3 and GC. 1,25D3 and GC combination enhanced tumor regression compared with 1,25D3 or GC alone. Conclusions 1,25D3 potentiates GC-mediated growth inhibition in human bladder cancer models in vitro and in vivo, which involves p73 induction and apoptosis. PMID:20564622

  7. 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.

  8. A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

    Science.gov (United States)

    Kiemeney, Lambertus A; Sulem, Patrick; Besenbacher, Soren; Vermeulen, Sita H; Sigurdsson, Asgeir; Thorleifsson, Gudmar; Gudbjartsson, Daniel F; Stacey, Simon N; Gudmundsson, Julius; Zanon, Carlo; Kostic, Jelena; Masson, Gisli; Bjarnason, Hjordis; Palsson, Stefan T; Skarphedinsson, Oskar B; Gudjonsson, Sigurjon A; Witjes, J Alfred; Grotenhuis, Anne J; Verhaegh, Gerald W; Bishop, D Timothy; Sak, Sei Chung; Choudhury, Ananya; Elliott, Faye; Barrett, Jennifer H; Hurst, Carolyn D; de Verdier, Petra J; Ryk, Charlotta; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Vineis, Paolo; Polidoro, Silvia; Guarrera, Simonetta; Sacerdote, Carlotta; Campagna, Marcello; Placidi, Donatella; Arici, Cecilia; Zeegers, Maurice P; Kellen, Eliane; Gutierrez, Berta Saez; Sanz-Velez, José I; Sanchez-Zalabardo, Manuel; Valdivia, Gabriel; Garcia-Prats, Maria D; Hengstler, Jan G; Blaszkewicz, Meinolf; Dietrich, Holger; Ophoff, Roel A; van den Berg, Leonard H; Alexiusdottir, Kristin; Kristjansson, Kristleifur; Geirsson, Gudmundur; Nikulasson, Sigfus; Petursdottir, Vigdis; Kong, Augustine; Thorgeirsson, Thorgeir; Mungan, N Aydin; Lindblom, Annika; van Es, Michael A; Porru, Stefano; Buntinx, Frank; Golka, Klaus; Mayordomo, José I; Kumar, Rajiv; Matullo, Giuseppe; Steineck, Gunnar; Kiltie, Anne E; Aben, Katja K H; Jonsson, Eirikur; Thorsteinsdottir, Unnur; Knowles, Margaret A; Rafnar, Thorunn; Stefansson, Kari

    2010-01-01

    Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 × 10−12). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC. PMID:20348956

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

    Science.gov (United States)

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

    2010-12-01

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

  10. Functional assays to determine the significance of two common XPC 3'UTR variants found in bladder cancer patients

    Directory of Open Access Journals (Sweden)

    Bishop D

    2011-06-01

    Full Text Available Abstract Background XPC is involved in the nucleotide excision repair of DNA damaged by carcinogens known to cause bladder cancer. Individuals homozygous for the variant allele of XPC c.1496C > T (p.Ala499Val were shown in a large pooled analysis to have an increased bladder cancer risk, and we found two 3'UTR variants, *611T > A and c.*618A > G, to be in strong linkage disequilibrium with c.1496T. Here we determined if these two 3'UTR variants can affect mRNA stability and assessed the impact of all three variants on mRNA and protein expression. Methods In vitro mRNA stability assays were performed and mRNA and protein expression measured both in plasmid-based assays and in lymphocytes and lymphoblastoid cell lines from bladder and breast cancer patients. Results The two 3'UTR variants were associated with reduced protein and mRNA expression in plasmid-based assays, suggesting an effect on mRNA stability and/or transcription/translation. A near-significant reduction in XPC protein expression (p = 0.058 was detected in lymphoblastoid cell lines homozygous for these alleles but no differences in mRNA stability in these lines was found or in mRNA or protein levels in lymphocytes heterozygous for these alleles. Conclusion The two 3'UTR variants may be the variants underlying the association of c.1496C > T and bladder cancer risk acting via a mechanism modulating protein expression.

  11. 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'. PMID:25263658

  12. 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'.

  13. What Are the Risk Factors for Bladder Cancer?

    Science.gov (United States)

    ... cancer Next Topic What causes bladder cancer? Bladder cancer risk factors A risk factor is anything that changes your ... make a person more likely to develop bladder cancer. Risk factors you can change Smoking Smoking is the most ...

  14. 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.

  15. [Specific types of bladder cancer].

    Science.gov (United States)

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

    2016-02-01

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

  16. A dosimetric comparison of 3D conformal vs intensity modulated vs volumetric arc radiation therapy for muscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Foroudi Farshad

    2012-07-01

    Full Text Available Abstract Background To compare 3 Dimensional Conformal radiotherapy (3D-CRT with Intensity Modulated Radiotherapy (IMRT with Volumetric-Modulated Arc Therapy (VMAT for bladder cancer. Methods Radiotherapy plans for 15 patients with T2-T4N0M0 bladder cancer were prospectively developed for 3-DCRT, IMRT and VMAT using Varian Eclipse planning system. The same radiation therapist carried out all planning and the same clinical dosimetric constraints were used. 10 of the patients with well localised tumours had a simultaneous infield boost (SIB of the primary tumour planned for both IMRT and VMAT. Tumour control probabilities and normal tissue complication probabilities were calculated. Results Mean planning time for 3D-CRT, IMRT and VMAT was 30.0, 49.3, and 141.0 minutes respectively. The mean PTV conformity (CI index for 3D-CRT was 1.32, for IMRT 1.05, and for VMAT 1.05. The PTV Homogeneity (HI index was 0.080 for 3D-CRT, 0.073 for IMRT and 0.086 for VMAT. Tumour control and normal tissue complication probabilities were similar for 3D-CRT, IMRT and VMAT. The mean monitor units were 267 (range 250–293 for 3D-CRT; 824 (range 641–1083 for IMRT; and 403 (range 333–489 for VMAT (P  Conclusions VMAT is associated with similar dosimetric advantages as IMRT over 3D-CRT for muscle invasive bladder cancer. VMAT is associated with faster delivery times and less number of mean monitor units than IMRT. SIB is feasible in selected patients with localized tumours.

  17. 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.

  18. 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

    To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review...... the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed......, as is chemotherapy for patients with metastatic urothelial cancer. The conference panel consisted of 10 medical oncologists and urologists from 3 continents who are experts in this field and who reviewed the English-language literature through October 2004. Relevant English-language literature was identified...

  19. Polymorphisms of the DNA repair genes XRCC1, XRCC3, XPD, interaction with environmental exposures, and bladder cancer risk in a case-control study in northern Italy.

    Science.gov (United States)

    Shen, Min; Hung, Rayjean J; Brennan, Paul; Malaveille, Christian; Donato, Francesco; Placidi, Donatella; Carta, Angela; Hautefeuille, Agnes; Boffetta, Paolo; Porru, Stefano

    2003-11-01

    Tobacco smoking and occupational exposures are the main known risk factors for bladder cancer, causing direct and indirect damage to DNA. Repair of DNA damage is under genetic control, and DNA repair genes may play a key role in maintaining genome integrity and preventing cancer development. Polymorphisms in DNA repair genes resulting in variation of DNA repair efficiency may therefore be associated with bladder cancer risk. A hospital-based case-control study was conducted in Brescia, Italy, to assess the relationship between polymorphisms in DNA repair genes XRCC1 (Arg(399)Gln), XRCC3 (Thr(241)Met), and XPD (Lys(751)Gln) and bladder cancer risk. A total of 201 male incident bladder cancer cases and 214 male controls with urological nonneoplastic diseases were recruited and frequency-matched on age, period, and hospital of recruitment. Detailed information was collected using a semistructured questionnaire on demographic, dietary, environmental, and occupational factors. Genotypes were determined by PCR-RFLP analysis. The XRCC3 codon 241 variant genotype exhibited a protective effect against bladder cancer [odds ratio (OR), 0.63; 95% confidence interval (CI), 0.42-0.93], which was prominent among heavy smokers (OR, 0.49; 95% CI, 0.28-0.88) but not among never and light smokers. No overall impact of the XRCC1 codon 399 polymorphism was found (OR, 0.86; 95% CI, 0.59-1.28), but a protective influence of the homozygous variant was suggested among heavy smokers (OR, 0.38; 95% CI, 0.14-1.02). XPD polymorphisms did not show an association with bladder cancer (OR, 0.92; 95% CI, 0.62-1.37). There was no statistical evidence of an interaction between these three genetic polymorphisms and either tobacco smoking or occupational exposure to polycyclic aromatic hydrocarbons and aromatic amines. The XRCC3 codon 241 polymorphism had an overall protective effect against bladder cancer that was most apparent among heavy smokers. Similarly, the XRCC1 codon 399 polymorphism also had

  20. 6p22.3 amplification as a biomarker and potential therapeutic target of advanced stage bladder cancer

    Science.gov (United States)

    Zhang, Jianmin; Underwood, Willie; Yang, Nuo; Frangou, Costa; Eng, Kevin; Head, Karen; Bollag, Roni J.; Kavuri, Sravan K.; Rojiani, Amyn M.; Li, Yingwei; Yan, Li; Hill, Annette; Woloszynska-Read, Anna; Wang, Jianmin; Liu, Song; Trump, Donald L.; Candace, Johnson S.

    2013-01-01

    Genetic and epigenetic alterations have been identified as to contribute directly or indirectly to the generation of transitional cell carcinoma of the urinary bladder (TCC-UB). In a comparative fashion much less is known about copy number alterations in TCC-UB, but it appears that amplification of chromosome 6p22 is one of the most frequent changes. Using fluorescence in situ hybridization (FISH) analyses, we evaluated chromosomal 6p22 amplification in a large cohort of bladder cancer patients with complete surgical staging and outcome data. We have also used shRNA knockdown candidate oncogenes in the cell based study. We found that amplification of chromosome 6p22.3 is significantly associated with the muscle-invasive transitional cell carcinoma of the urinary bladder (TCC-UB) (22%) in contrast to superficial TCC-UB (9%) (p=7.2-04). The rate of 6p22.3 amplification in pN>1 patients (32%) is more than twice that in pN0 (16%) patients (p=0.05). Interestingly, we found that 6p22.3 amplification is as twice as high (p=0.0201) in African American (AA) than European American (EA) TCC-UB patients. Moreover, we showed that the expression of some candidate genes (E2F3, CDKAL1 and Sox4) in the 6p22.3 region is highly correlated with the chromosomal amplification. In particular, knockdown of E2F3 inhibits cell proliferation in a 6p22.3-dependent manner, whereas knockdown of CDKAL1 and Sox4 has no effect on cell proliferation. Using gene expression profiling, we further identified some common as well as distinctive subset targets of the E2F3 family members. In summary, our data indicate that E2F3 is a key regulator of cell proliferation in a subset of bladder cancer and the 6p22.3 amplicon is a biomarker of aggressive phenotype in this tumor type. PMID:24231253

  1. Dietary factors associated with bladder cancer

    OpenAIRE

    Piyathilake, Chandrika

    2016-01-01

    It is biologically plausible for dietary factors to influence bladder cancer risk considering that beneficial as well as harmful components of a diet are excreted through the urinary tract and in direct contact with the epithelium of the bladder. However, studies that investigated the association between dietary factors and bladder cancer (BC) risk have largely reported inconsistent results. The macronutrient intake and risk of BC could have yield inconsistent results across studies because o...

  2. Amygdalin Influences Bladder Cancer Cell Adhesion and Invasion In Vitro

    OpenAIRE

    Jasmina Makarević; Jochen Rutz; Eva Juengel; Silke Kaulfuss; Igor Tsaur; Karen Nelson; Jesco Pfitzenmaier; Axel Haferkamp; 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...

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

    Science.gov (United States)

    Fukushima, Shoji; Wanibuchi, Hideki

    2000-01-01

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

  4. 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. 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.

  6. A dosimetric comparison of 3D conformal vs intensity modulated vs volumetric arc radiation therapy for muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    To compare 3 Dimensional Conformal radiotherapy (3D-CRT) with Intensity Modulated Radiotherapy (IMRT) with Volumetric-Modulated Arc Therapy (VMAT) for bladder cancer. Radiotherapy plans for 15 patients with T2-T4N0M0 bladder cancer were prospectively developed for 3-DCRT, IMRT and VMAT using Varian Eclipse planning system. The same radiation therapist carried out all planning and the same clinical dosimetric constraints were used. 10 of the patients with well localised tumours had a simultaneous infield boost (SIB) of the primary tumour planned for both IMRT and VMAT. Tumour control probabilities and normal tissue complication probabilities were calculated. Mean planning time for 3D-CRT, IMRT and VMAT was 30.0, 49.3, and 141.0 minutes respectively. The mean PTV conformity (CI) index for 3D-CRT was 1.32, for IMRT 1.05, and for VMAT 1.05. The PTV Homogeneity (HI) index was 0.080 for 3D-CRT, 0.073 for IMRT and 0.086 for VMAT. Tumour control and normal tissue complication probabilities were similar for 3D-CRT, IMRT and VMAT. The mean monitor units were 267 (range 250–293) for 3D-CRT; 824 (range 641–1083) for IMRT; and 403 (range 333–489) for VMAT (P < 0.05). Average treatment delivery time were 2:25min (range 2:01–3:09) for 3D-CRT; 4:39 (range 3:41–6:40) for IMRT; and 1:14 (range 1:13–1:14) for VMAT. In selected patients, the SIB did not result in a higher dose to small bowel or rectum. VMAT is associated with similar dosimetric advantages as IMRT over 3D-CRT for muscle invasive bladder cancer. VMAT is associated with faster delivery times and less number of mean monitor units than IMRT. SIB is feasible in selected patients with localized tumours

  7. Bladder cancer arising in a spina bifida patient.

    Science.gov (United States)

    Game, X; Villers, A; Malavaud, B; Sarramon, J

    1999-11-01

    We report the case of a 52-year-old patient with spina bifida, neurologic bladder, and a history of recurrent urinary tract infections (UTIs) in whom a bladder cancer was incidentally discovered. Cytology, cystoscopy, and cystography showed nonspecific, extensive inflammatory lesions. Cystography demonstrated a complex of diverticulae and cellules. Pathologic examination of a diverticulectomy specimen revealed a grade III pT3b transitional and squamous cell carcinoma. Because of the similar disease causation (recurrent UTIs, stones, and indwelling catheterization), we suggest extension of the guidelines proposed for patients with spinal cord injuries (ie, annual serial bladder biopsies) to patients with nontraumatic neurogenic bladder. PMID:10754152

  8. Urinary bladder cancer: role of MR imaging.

    Science.gov (United States)

    Verma, Sadhna; Rajesh, Arumugam; Prasad, Srinivasa R; Gaitonde, Krishnanath; Lall, Chandana G; Mouraviev, Vladimir; Aeron, Gunjan; Bracken, Robert B; Sandrasegaran, Kumaresan

    2012-01-01

    Urinary bladder cancer is a heterogeneous disease with a variety of pathologic features, cytogenetic characteristics, and natural histories. It is the fourth most common cancer in males and the tenth most common cancer in females. Urinary bladder cancer has a high recurrence rate, necessitating long-term surveillance after initial therapy. Early detection is important, since up to 47% of bladder cancer-related deaths may have been avoided. Conventional computed tomography (CT) and magnetic resonance (MR) imaging are only moderately accurate in the diagnosis and local staging of bladder cancer, with cystoscopy and pathologic staging remaining the standards of reference. However, the role of newer MR imaging sequences (eg, diffusion-weighted imaging) in the diagnosis and local staging of bladder cancer is still evolving. Substantial advances in MR imaging technology have made multiparametric MR imaging a feasible and reasonably accurate technique for the local staging of bladder cancer to optimize treatment. In addition, whole-body CT is the primary imaging technique for the detection of metastases in bladder cancer patients, especially those with disease that invades muscle. PMID:22411938

  9. Urothelial Bladder Cancer with Cavitary Lung Metastases

    OpenAIRE

    Anil Kurian; Jason Lee; Abraham Born

    2011-01-01

    Transitional cell carcinoma (TCC) of the bladder tends to remain superficial; however, in 5% to 20% of cases, it progresses to muscle invasion and, more rarely, can metastasize. TCC of the bladder primarily spreads via regional lymphatics. The most common sites of distant metastases of TCC are the liver, lung, mediastinum and bone. Long-term survival of patients with metastatic bladder cancer is rare. Patterns of pulmonary metastasis include multiple nodules, a solitary mass or interstitial m...

  10. Effect of Ad-p16 Combined with CDDP or As2O3 on Human Bladder Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    朱朝辉; 邢诗安; 林晨

    2003-01-01

    Summary: To evaluate the therapeutic efficiency of combined use of p16-expressing adenovirus and chemotherapeutic agents CDDP or As2O3 on human bladder cancer cell line E J, the human bladder cancer cell line EJ were transfected with adenovirus-mediated p16 gene (Ad-p16), with administration of cisplatin (CDDP) or arsenic trioxide (As2O3). The cell growth, morphological changes, cell cycle, apoptosis and molecular changes were measured using cell counting, reverse microscopy, flow cytometry, cloning formation, immunocytochemical assays and in vivo therapy experiments to evaluate the therapeutic efficacy of such combined regimen. Ad-p16 transfer and CDDP or As2O3 administration to EJ cells could exert substantially stronger therapeutic effects than the single agent treatment. Especially in in vivo experiments, combined administration of p16 and CDDP or As2O3 induced almost tumor diminish compared to the partial tumor diminish induced by single agent. Moreover,delivery of Ad-p16, or administration of minimal-dose CDDP or As2O3 or combined regimen could induce massive apoptosis of EJ cell. Cell cycle analysis demonstrated that administration of CDDP or As2O3 remarkably arrested EJ cell in G1 prior to apoptotic cell death. When treated with combined regimen, cells were arrested in G1 to a greater extent prior to apoptotic cell death. It is concluded that after introduction into EJ cell, Ad-p16 shows enhanced therapeutic efficacy for EJ cell when used in combination with CDDP or As2O3.

  11. 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

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

    Science.gov (United States)

    2016-06-09

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

  13. A bladder preservation regimen using intra-arterial chemotherapy and radiotherapy for invasive bladder cancer. A prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Miyanaga, Naoto; Akaza, Hideyuki [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine; Okumura, Toshiyuki [and others

    2000-02-01

    A prospective study was performed to investigate combined treatment with intra-arterial chemotherapy and radiation therapy for bladder preservation in locally invasive bladder cancer. Patients with invasive bladder cancer, stage T2-3N0M0, were included in the study. lntra-arterial chemotherapy was performed with three injections of methotrexate and cisplatin at 3-week intervals. Simultaneously, the patients underwent X-ray irradiation (40 Gy) of the small pelvic space. Where a post-treatment transurethral resection (TUR) biopsy showed no residual tumor, the tumor site was irradiated by a 30 Gy proton beam and the bladder was preserved. Where tumors remained, radical cystectomy was performed. Between 1990 and 1996, 42 patients were treated according to this protocol. Post-treatment TUR biopsy and urine cytology showed no residual tumors in 39 of 42 cases (93%). The bladder was preserved in accordance with the study protocol in 36 cases. A median follow-up of 38 months showed 3-year non-recurrence in 72% of bladder-preserved patients and the rate of bladder preservation was 84%. The nine recurrences included eight cases of superficial bladder recurrence. One cancer death occurred among the bladder-preservation patients, giving 3-year survival and cause-specific survival rates of 84% and 100%, respectively. Although bladder function decreased slightly in compliance, bladder capacity was retained in almost all cases. This regimen is useful for bladder preservation in T2-3 locally invasive bladder cancer. Information from more cases and the results of more long-term observations are needed, as is an evaluation of appropriate subject selection and factors associated with quality of life issues, particularly regarding bladder function. (author)

  14. A component of green tea (-)-epigallocatechin-3-gallate, promotes apoptosis in T24 human bladder cancer cells via modulation of the PI3K/Akt pathway and Bcl-2 family proteins

    International Nuclear Information System (INIS)

    Bladder cancer is the fourth most common cancer in men and ninth most common in women. It has a protracted course of progression and is thus an ideal candidate for chemoprevention strategies and trials. This study was conducted to evaluate the chemopreventive/antiproliferative potential of (-)-epigallocatechin gallate (EGCG, the major phytochemical in green tea) against bladder cancer and its mechanism of action. Using the T24 human bladder cancer cell line, we found that EGCG treatment caused dose- and time-dependent inhibition of cellular proliferation and cell viability, and induced apoptosis. Mechanistically, EGCG inhibits phosphatidylinositol 3'-kinase/Akt activation that, in turn, results in modulation of Bcl-2 family proteins, leading to enhanced apoptosis of T24 cells. These findings suggest that EGCG may be an important chemoprevention agent for the management of bladder cancer

  15. TOX3 (TNRC9) Over Expression in Bladder Cancer Cells Decreases Cellular Proliferation and Triggers an Interferon-Like Response

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Mansilla Castaño, Francisco; Dyrskjøt, Lars;

    2013-01-01

    identification and immunoprecipitation studies were used for DNA binding studies. Results: Microarray transcript profiling of 89 bladder biopsies showed a significant up-regulation of TOX3 (pmuscle invasive (Ta-T1) bladder tumors compared to muscle-invasive (T2-T4) bladder tumors and normal...... expressing cell extracts with an artificial “GAS”- DNA element resulted in an enrichment of the GAS containing DNA-sequence, providing evidence for a potential interaction of TOX3 with the GAS-sequence of STAT1. Conclusions: These results provide evidence for an alternative activation of the downstream...

  16. TOX3 (TNRC9) overexpression in bladder cancer cells decreases cellular proliferation and triggers an interferon-like response

    DEFF Research Database (Denmark)

    Birkenkamp-Demtröder, Karin; Mansilla, Francisco; Andersen, Lars Dyrskjøt;

    2013-01-01

    identification and immunoprecipitation studies were used for DNA binding studies. Results Microarray transcript profiling of 89 bladder biopsies showed a significant upregulation of TOX3 (pmuscle invasive (Ta-T1) bladder tumors compared to muscle-invasive (T2-T4) bladder tumors and normal...... cell extracts with an artificial “GAS”-DNA element resulted in an enrichment of the GAS containing DNA-sequence, providing evidence for a potential interaction of TOX3 with the GAS-sequence of STAT1. Conclusions These results provide evidence for an alternative activation of the downstream interferon...

  17. Radical cystectomy for the treatment of T1 bladder cancer: the Canadian Bladder Cancer Network experience

    Science.gov (United States)

    Chalasani, Venu; Kassouf, Wassim; Chin, Joseph L.; Fradet, Yves; Aprikian, Armen G.; Fairey, Adrian S.; Estey, Eric; Lacombe, Louis; Rendon, Ricardo; Bell, David; Cagiannos, Ilias; Drachenberg, Darrell; Lattouf, Jean-Baptiste; Izawa, Jonathan I.

    2011-01-01

    Background: Radical cystectomy may provide optimal survival outcomes in the management of clinical T1 bladder cancer. We present our data from a large, multi-institutional, contemporary Canadian series of patients who underwent radical cystectomy for clinical T1 bladder cancer in a single-payer health care system. Methods: We collected a pooled database of 2287 patients who underwent radical cystectomy between 1993 and 2008 in 8 different centres across Canada; 306 of these patients had clinical T1 bladder cancer. Survival data were analyzed using Kaplan-Meier method and Cox regression analysis. Results: The median age of patients was 67 years with a mean follow-up time of 35 months. The 5-year overall, disease-specific and disease-free survival was 71%, 77% and 59%, respectively. The 10-year overall and disease-specific survival were 60% and 67%, respectively. Pathologic stage distribution was p0: 32 (11%), pT1: 78 (26%), pT2: 55 (19%), pT3: 60 (20%), pT4: 27 (9%), pTa: 16 (5%), pTis: 28 (10%), pN0: 215 (74%) and pN1-3: 78 (26%). Only 12% of patients were given adjuvant chemotherapy. On multivariate analysis, only margin status and pN stage were independently associated with overall, disease-specific and disease-free survival. Interpretation: These results indicate that clinical T1 bladder cancer may be significantly understaged. Identifying factors associated with understaged and/or disease destined to progress (despite any prior intravesical or repeat transurethral therapies prior to radical cystectomy) will be critical to improve survival outcomes without over-treating clinical T1 disease that can be successfully managed with bladder preservation strategies. PMID:21470529

  18. Survival after cystectomy in infiltrating bladder cancer

    International Nuclear Information System (INIS)

    We reviewed the results of infiltrating bladder cancer treated by radical cystectomy to evaluate cancer treated by radical cystectomy to evaluate survival. Between January 1989 and December 1992, a total of 58 consecutive cystectomies or anterior pelvic exenterations performed on 48 men and 10 women (mean age 63.2 years) in our department were retrospectively evaluated. Four patients were lost to follow-up and the mean follow-up was 72 months. Pathologic staging was as follows: stage pTO,A,1: 13.5%, stage pT2: 17.5%, stage pT3a: 12%, stage pT3b: stage pT4: 21%. The year probability of the overall survival was 60% for pT2-p T3a patients, 15% for pT3b patients, and 9% for pT4 patients, respectively. Overall, 53.5% of patients died of cancer, 7.5% of intercurrent disease, and 39% were alive. The cancer related death rate was 12% for pT2-pT3a patients, and 82% for pT3b-pT4 patients. The 5- year probability of specific survival was 80% for pT2-pT3a patients, 15% for pT3b patients and 9% for pT4 patients, respectively. Infiltrating bladder cancer still has a high mortality rate. Radical cystectomy may be considered to be a curative procedure for stages pT2 and pT3a. Adjuvant chemotherapy and/or radiotherapy seem necessary at stages pT3 and pT4. Preoperative criteria need to be better defined to reduce understanding. (authors)

  19. CHEMOTHERAPY FOR MUSCLE INVASIVE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    I. G. Rusakov

    2014-08-01

    Full Text Available The paper considers treatment regimens for metastatic bladder cancer (MBC and gives the data of trials of the efficiency of using different chemotherapy schemes and regimens in patients with MBC.

  20. Narrow band imaging for bladder cancer

    OpenAIRE

    Thomas Y. Hsueh; Allen W. Chiu

    2016-01-01

    Narrow band imaging (NBI) is a newly developed technology aiming to provide additional endoscopic information for patients with bladder cancer. This review focuses on the diagnostic accuracy and treatment outcome using NBI cystoscopy for the treatment of non-muscle invasive bladder cancer. Current results showed improved sensitivity of NBI cystoscopy compared to conventional white light cystoscopy, although lower specificity and increased false-positive results were reported using NBI cystosc...

  1. Thulium laser treatment for bladder cancer

    OpenAIRE

    Wei Wang; Haitao Liu; Shujie Xia

    2016-01-01

    Recent innovations in thulium laser techniques have allowed application in the treatment of bladder cancer. Laser en bloc resection of bladder cancer is a transurethral procedure that may offer an alternative to the conventional transurethral resection procedure. We conducted a review of basic thulium laser physics and laser en bloc resection procedures and summarized the current clinical literature with a focus on complications and outcomes. Literature evidence suggests that thulium laser te...

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

    Science.gov (United States)

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

    2016-05-10

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

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

    OpenAIRE

    Gulay Ceylan

    2016-01-01

    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 canc...

  4. Role of the FGFR3 gene mutation status in predicting progression of non-muscle-invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    A. I. Rolevich

    2015-01-01

    Full Text Available A prospective study was conducted to assess the prognostic value of FGFR3 gene mutation status in patients with non-muscle invasive bladder cancer. A total of 265 patients were included in the study. FGFR3 gene mutations were found in 168 (63.4 % cases. FGFR3 mutation rate was significantly higher in low-grade tumors (p = 0.00 004. With a median follow-up of 34 months hazard ratio of progression in FGFR3 mutant cases compared to FGFR3 wild type was 0.50 (95 % CI 0.17–1.49; p = 0.21. In the subgroup analysis, it was found that FGFR3 mutations in patients with T1 high grade tumors (n = 41 were associated with a significantly better prognosis: 3-year progression-free survival (PFS in FGFR3 mutant cases (n = 17 was 100 % compared to 71.2 % (95 % CI 42.8–99.6 % in the absence of mutations (n = 24. For other subgroups (Ta, T1 low grade no statistically significant difference in PFS by FGFR3 mutation status was noted.

  5. 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

  6. 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.

  7. Contrast-enhanced dynamic and diffusion-weighted MR imaging at 3.0 T to assess aggressiveness of bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Guoxing, E-mail: sheasthospital@163.com [Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120 (China); Chen, Xiao, E-mail: chx_win@163.com [Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120 (China); Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029 (China); Zhang, Jianhua [Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120 (China); Zhu, Jingqi, E-mail: zjh1830@easthospital.cn [Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120 (China); Zong, Genlin, E-mail: zgl0577@easthospital.cn [Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120 (China); Wang, Zhongqiu, E-mail: zhq2001us@163.com [Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029 (China)

    2014-11-15

    Highlights: • Wash out rate is associated with the aggressiveness of bladder cancer (BC). • Apparent diffusion coefficient (ADC) value could be used to assess the aggressiveness of BC. • The diagnostic accuracy of aggressiveness of BC using ADC was better than semi-quantitative parameters. • Our data showed a good diagnostic performance of ADC and wash-out together in assessing BC aggressiveness. - Abstract: Background: Diffusion weighted magnetic resonance imaging (DWI) and dynamic contrast-enhanced (DCE) MRI have been considered useful for pathological staging and histological grading in bladder cancer. To our knowledge, no study has combined the two imaging modalities together to assess aggressiveness of bladder cancer. Objective: To assess the clinical aggressiveness of bladder cancer with DCE MRI and DWI at 3.0 T. Materials and methods: A total of 59 patients with 69 pathologically confirmed tumor lesions were included in this study. All patients underwent MR examination at 3.0 T basing on DWI and DCE imaging. Tumor staging and histological grade were evaluated. The aggressiveness of bladder cancer was classified as low-, intermediate-, or high-aggressiveness according to its pathological phenotype. Apparent diffusion coefficient (ADC) value and semi-quantitative parameters (wash-in rate and wash-out rate) were determined. The correlation between clinical aggressiveness and ADC value, wash-in rate and wash-out rate were analyzed. In addition, the diagnostic accuracy of the diffusion and semi-quantitative parameters were estimated using receiver operating characteristic curve (ROC). Results: Aggressiveness of bladder cancer is negatively correlated with ADC value (r = −0.705, p < 0.0001) and wash-out rate (r = −0.719, p < 0.0001). The tumor ADC value is positively correlated with wash-out rate (r = 0.555, p < 0.0001). The diagnostic specificity and accuracy using tumor ADC value and wash-out for the tumor with size <24 mm were better than that

  8. Integrated genetic and epigenetic analysis of bladder cancer reveals an additive diagnostic value of FGFR3 mutations and hypermethylation events

    DEFF Research Database (Denmark)

    Serizawa, Reza R; Ralfkiaer, Ulrik; Steven, Kenneth;

    2011-01-01

    screened FGFR3, PIK3CA, TP53, HRAS, NRAS and KRAS for mutations and quantitatively assessed the methylation status of APC, ARF, DBC1, INK4A, RARB, RASSF1A, SFRP1, SFRP2, SFRP4, SFRP5 and WIF1 in a prospective series of tumor biopsies (N = 105) and urine samples (N = 113) from 118 bladder tumor patients. We...

  9. 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.

  10. 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

  11. Contemporary management of low-risk bladder cancer

    NARCIS (Netherlands)

    Falke, J.; Witjes, J.A.

    2011-01-01

    Bladder cancer comprises a heterogeneous group of tumors, the majority of which are non-muscle-invasive bladder cancer (NMIBC) at initial presentation. Low-risk bladder cancer--defined as pTa low-grade papillary tumors--is the type of NMIBC with the most favorable oncologic outcome. Although the ris

  12. Bladder cancer and occupational exposure to leather.

    OpenAIRE

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

    1986-01-01

    A large case-control study of bladder cancer (2982 cases; 5782 controls) included information about occupational exposure to leather. Occupational histories of exposed white study subjects were reviewed and 150 were determined to have had "true" on the job exposure to leather. The odds ratio estimate (OR) of bladder cancer associated with such exposure in white subjects (n = 8063) was 1.4 (95% confidence limits = 1.0, 1.9) after adjustment for sex, age, and cigarette smoking. The risk was hig...

  13. 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

  14. COMBINED TREATMENT OF LOCALLY-ADVANCED BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    I. V. Chernyshev

    2015-01-01

    Full Text Available Bladder cancer (BC is an important clinical and scientific challenge. In 2013, in Russia, the absolute number of patients with first-ever diagnosis of bladder cancer was 12 992 people. There is an increasing proportion of detection of bladder cancer stage I–II disease patterns: 2003–50.8% in 2013–69.6%, while the number of newly diagnosed patients in III and IV clinical stages remains at 30%. The proportion of individuals who completed the treatment of the number of newly diagnosed patients with bladder cancer in 2013, was as follows: only surgical method — 65.4%, 33.5% combined. Purpose. Improvement of the results of treatment of patients with locally advanced bladder cancer. Materials and methods. The main treatment for muscle-invasive bladder cancer is radical cystectomy. In the combined treatment of bladder cancer chemotherapy is the component that systemic exposure to the tumor, the way of regional and distant metastases. The study included 132 patients with locally advanced bladder cancer who were treated for 2005–2013, divided into four groups: NACT + CE — 27 people (20.5%, CE + ACT — 21 (15.9%, NACT + CE + ACT — 21 (15.9% only CE — 63 (47.7%. An important component of treatment has been the use of platinum (cisplatin or carboplatin in Schemes M–VAC and GP. An objective response is possible in 44.7%, and the stabilization process in 40.4% of patients.Results. The clinical effect is evaluated in all patients. In the group of NACT 21% of patients survived for more than 4 years, but did not survive the 5‑year mark. In the group of CE + ACT the indicator achieved only 3‑year survival rate, which amounted to 43%. In the group of CE — none of the patients did not live up to 3 years, with 2‑year survival rate was 30%. In the group of ACT + NCT + CE 3 patients (15% were alive at the time, passed the threshold of the 5‑year survival rate, there is no progression of cancer.Conclusion. Combined treatment mode NACT

  15. 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...

  16. Screening for Bladder and Other Urothelial Cancers

    Science.gov (United States)

    ... Using tobacco , especially smoking cigarettes. Having a family history of bladder cancer. Having certain changes in the genes . Being exposed to paints, dyes, metals or petroleum products in the workplace. Past treatment with radiation therapy to the pelvis or with certain anticancer drugs, ...

  17. Fibroblast growth factor receptor 3 interacts with and activates TGFβ-activated kinase 1 tyrosine phosphorylation and NFκB signaling in multiple myeloma and bladder cancer.

    Directory of Open Access Journals (Sweden)

    Lisa Salazar

    Full Text Available Cancer is a major public health problem worldwide. In the United States alone, 1 in 4 deaths is due to cancer and for 2013 a total of 1,660,290 new cancer cases and 580,350 cancer-related deaths are projected. Comprehensive profiling of multiple cancer genomes has revealed a highly complex genetic landscape in which a large number of altered genes, varying from tumor to tumor, impact core biological pathways and processes. This has implications for therapeutic targeting of signaling networks in the development of treatments for specific cancers. The NFκB transcription factor is constitutively active in a number of hematologic and solid tumors, and many signaling pathways implicated in cancer are likely connected to NFκB activation. A critical mediator of NFκB activity is TGFβ-activated kinase 1 (TAK1. Here, we identify TAK1 as a novel interacting protein and target of fibroblast growth factor receptor 3 (FGFR3 tyrosine kinase activity. We further demonstrate that activating mutations in FGFR3 associated with both multiple myeloma and bladder cancer can modulate expression of genes that regulate NFκB signaling, and promote both NFκB transcriptional activity and cell adhesion in a manner dependent on TAK1 expression in both cancer cell types. Our findings suggest TAK1 as a potential therapeutic target for FGFR3-associated cancers, and other malignancies in which TAK1 contributes to constitutive NFκB activation.

  18. Probiotics, dendritic cells and bladder cancer.

    Science.gov (United States)

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

    2012-06-01

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

  19. 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 ...... photoreceptor dysfunction, confirmed by ERG, should alert to a possible remote effect of known or occult malignancy. In the latter, PET-CT may be exploited as a powerful diagnostic tool....

  20. 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.

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

    Science.gov (United States)

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

    2012-02-01

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

  2. Urothelial bladder cancer with cavitary lung metastases.

    Science.gov (United States)

    Kurian, Anil; Lee, Jason; Born, Abraham

    2011-01-01

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

  3. Urothelial Bladder Cancer with Cavitary Lung Metastases

    Directory of Open Access Journals (Sweden)

    Anil Kurian

    2011-01-01

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

  4. 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

    mm) for bladder planning target volume (PTV). The goal of this retrospective study is to define, evaluate and optimize new patient-specific anisotropic PTVs (a-PTVs) using deformable image registration (DIR) between empty and full bladder computed tomography (CT) scans. This will provide an ART...... 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...... bladder cancer patients and a total of 100 fractions. It was found that the smaller a-PTV, a-PTV4 and a-PTV3, were appropriate in 87% of the fractions, while a-PTV2 and a-PTV1 were required in 12% of the fractions respectively. The use of the a-PTVs reduced the PTV volume by 32% (28-36%) as compared...

  5. Tetrachloroethylene exposure and bladder cancer risk

    DEFF Research Database (Denmark)

    Vlaanderen, Jelle; Straif, Kurt; Ruder, Avima;

    2014-01-01

    BACKGROUND: In 2012, the International Agency for Research on Cancer classified tetrachloroethylene, used in the production of chemicals and the primary solvent used in dry cleaning, as "probably carcinogenic to humans" based on limited evidence of an increased risk of bladder cancer in dry...... cleaners. OBJECTIVES: We assessed the epidemiological evidence for the association between tetrachloroethylene exposure and bladder cancer from published studies estimating occupational exposure to tetrachloroethylene or in workers in the dry-cleaning industry. METHODS: Random-effects meta-analyses were...... carried out separately for occupational exposure to tetrachloroethylene and employment as a dry cleaner. We qualitatively summarized exposure-response data because of the limited number of studies available. RESULTS: The meta-relative risk (mRR) among tetrachloroethylene-exposed workers was 1.08 (95% CI...

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

    International Nuclear Information System (INIS)

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

  7. Gemcitabine and cisplatin in locally advanced and metastatic bladder cancer; 3- or 4-week schedule?

    DEFF Research Database (Denmark)

    Als, Anne Birgitte; Sengeløv, Lisa; Von Der Maase, Hans

    2008-01-01

    BACKGROUND: Chemotherapy with gemcitabine and cisplatin (GC) is an active regimen in advanced transitional cell carcinoma (TCC). Traditionally, GC has been administered as a 4-week schedule. However, an alternative 3-week schedule may be more feasible. Long-term survival data for the alternative 3......-week schedule and comparisons of the feasibility and toxicity between the two schedules have not previously been published. MATERIAL AND METHODS: We performed a retrospective analysis of patients with stage IV TCC, treated with GC by a standard 4-week or by an alternative 3-week schedule. RESULTS...

  8. General Information about Bladder Cancer

    Science.gov (United States)

    ... Español 1-800-4-CANCER Live Chat Publications Dictionary Menu Contact Dictionary Search About Cancer Causes and Prevention Risk Factors ... Contacts Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training ...

  9. Studies of experimental bladder tumors, 3

    International Nuclear Information System (INIS)

    Enzymatologic, histochemical and histologic investigations were performed on the effects of SLA, a β-glucoronidase inhibitor, and Linaic irradiation in an experimental BBN bladder tumor of rats. Bladder tumors were macroscopically thumb-head size in the cases with no treatment of with SLA application, but were shrunk by roentgen irradiation. The number of the rats with reduced tumor was respectively 3 in the group with roentgen irradiation. S-LDH activity of the cancer-carrying animals was markedly elevated as compared with that of the normal rat. SLA application caused no change in S-LDH activity of cancer-carrying animals, but roentgen irradiation resulted in a marked decrease in S-LDH activity of the similar animals with bladder tumors. The level of this decrease was dependent on the dosage of one time irradiation; no change was observed by 200, 300 and 500 rad, little decrease was seen by 750 rad, and marked decrease was observed after 1,000 and 1,500 rad radiation. Histological observation of the effects of irradiation could be summarized as follows. Histological changes were seen in the cases of macroscopic shrinkage by 3,000 rad irradiation. In this group, an individual variation was noticed not only macroscopically but microscopically. One time irradiation of 200, 300 and 500 rad resulted in no histological change, but that of 750, 1,000, and 1,500 rad caused a slight, but not marked, histological change. Tissue distribution of β-glucuronidase was examined by means of Naphthol-AS-BI-glucuronide method in the group without any treatment and the group with SLA administration. β-glucuronidase activity was noticed in the epithelial cells and interstitial stroma of the tumor tissue, but the effect of SLA on β-glucuronidase activity was not observed histochemically. (author)

  10. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

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

    2006-01-01

    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...... could be detected in the urine by Western blotting; ADAM12 was present in higher levels in the urine from patients with bladder cancer compared with urine from healthy individuals. Significantly, following removal of tumor by surgery, in most bladder cancer cases examined, the level of ADAM12...

  11. 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

  12. 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.

  13. Paraneoplastic retinopathy associated with occult bladder cancer

    Directory of Open Access Journals (Sweden)

    M Nivean

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

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

    OpenAIRE

    Letašiová Silvia; Medveďová Alžbeta; Šovčíková Andrea; Dušinská Mária; Volkovová Katarína; Mosoiu Claudia; Bartonová Alena

    2012-01-01

    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 publish...

  16. Well Water a Suspected Cause of Bladder Cancer in New England

    Science.gov (United States)

    ... a Suspected Cause of Bladder Cancer in New England Researchers believe arsenic exposure might contribute to higher- ... bladder cancer risk among people in three New England states, a new study suggests. Bladder cancer rates ...

  17. 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.

  18. Hair Dye Use and Risk of Bladder Cancer in the New England Bladder Cancer Study

    OpenAIRE

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

    2011-01-01

    Aromatic amine components in hair dyes, and polymorphisms in genes that encode enzymes responsible for hair dye metabolism, may be related to bladder cancer risk. We evaluated the association between hair dye use and bladder cancer risk and effect modification by NAT1, NAT2, GSTM1, and GSTT1 genotypes in a population-based case-control study of 1,193 incident cases and 1,418 controls from Maine, Vermont, and New Hampshire enrolled between 2001 and 2004. Individuals were interviewed in person ...

  19. 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

  20. Oncolytic Viruses in the Treatment of Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Kyle G. Potts

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

  2. 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.

  3. Cancer of the urinary bladder category T2, T3, (N/sub x/M/sub o/) treated by interstitial radium implant: second report

    International Nuclear Information System (INIS)

    Three-hundred-twenty-eight patients with bladder cancer category T2N/sub x/M/sub o/ have been treated by 3 times 3.5 Gy external irradiation followed by a radium implant. Overall 5- and 10-year survival in the T2 category are 56% adn 37%. In the T3 category they are 39% adn 13%, respectively. The intercurrent death (i.e. without evidence of bladder malignancy) corrected acuarial survival percentage in the T2 category is 75% at 5 years and 69% at 10 years. The corresponding percentages in the T3 category are 62% and 59%. Prognosis is worsened by the following factors: more than 1 diagnostic transurethral resection, a pathological intravenous pyelography, non-papillary structure and poor degree of differentiation of the growth. Prognosis in category T3, as compared with category T2, is worse because of the prevalence of bad prognosticators in this T3 category. Therapeutic adaptation to thesse findings might improve prognosis in the future

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

    Energy Technology Data Exchange (ETDEWEB)

    Orsatti, M.; Franzone, P.; Giudici, S. [Istituto Nazionale per la Ricerca sul Cancro, Genova (Switzerland)] [and others

    1995-08-30

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

  5. Bladder cancer and reproductive factors among women in Spain

    OpenAIRE

    Huang, An-Tsun; Kogevinas, Manolis; Silverman, Debra T.; Malats, Nủria; Rothman, Nathaniel; Tardón, Adonina; Serra, Consol; García-Closas, Reina; Carrato, Alfredo; Cantor, Kenneth P.

    2009-01-01

    Hormonal factors, possibly related to reproductive characteristics, may play a role in the risk of bladder cancer among women. To study this, we investigated the effects of reproductive factors on female bladder cancer risk. Information on reproductive and other risk factors was gathered in personal interviews from 152 female cases and 166 matched controls from 18 hospitals in five regions of Spain during 1998–2001. Logistic regression was used to estimate the association between bladder canc...

  6. 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.

  7. Human insulin does not increase bladder cancer risk.

    Directory of Open Access Journals (Sweden)

    Chin-Hsiao Tseng

    Full Text Available BACKGROUND: Whether human insulin can induce bladder cancer is rarely studied. METHODS: The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 785,234 patients with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Users of pioglitazone were excluded and the period since the initiation of insulin glargine (marketed after the entry date in Taiwan was not included in the calculation of follow-up. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, duration of therapy and cumulative dose were calculated and the hazard ratios were estimated by Cox regression. RESULTS: There were 87,940 ever-users and 697,294 never-users, with respective numbers of incident bladder cancer of 454 (0.52% and 3,330 (0.48%, and respective incidence of 120.49 and 94.74 per 100,000 person-years. The overall hazard ratios (95% confidence intervals indicated a significant association with insulin in the age-sex-adjusted models [1.238 (1.122-1.366], but not in the model adjusted for all covariates [1.063 (0.951-1.187]. There was also a significant trend for the hazard ratios for the different categories of the dose-response parameters in the age-sex-adjusted models, which became insignificant when all covariates were adjusted. CONCLUSIONS: This study relieves the concern of a bladder cancer risk associated with human insulin. Appropriate adjustment for confounders is important in the evaluation of cancer risk associated with a medication.

  8. Human Insulin Does Not Increase Bladder Cancer Risk

    Science.gov (United States)

    Tseng, Chin-Hsiao

    2014-01-01

    Background Whether human insulin can induce bladder cancer is rarely studied. Methods The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 785,234 patients with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Users of pioglitazone were excluded and the period since the initiation of insulin glargine (marketed after the entry date in Taiwan) was not included in the calculation of follow-up. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, duration of therapy and cumulative dose) were calculated and the hazard ratios were estimated by Cox regression. Results There were 87,940 ever-users and 697,294 never-users, with respective numbers of incident bladder cancer of 454 (0.52%) and 3,330 (0.48%), and respective incidence of 120.49 and 94.74 per 100,000 person-years. The overall hazard ratios (95% confidence intervals) indicated a significant association with insulin in the age-sex-adjusted models [1.238 (1.122–1.366)], but not in the model adjusted for all covariates [1.063 (0.951–1.187)]. There was also a significant trend for the hazard ratios for the different categories of the dose-response parameters in the age-sex-adjusted models, which became insignificant when all covariates were adjusted. Conclusions This study relieves the concern of a bladder cancer risk associated with human insulin. Appropriate adjustment for confounders is important in the evaluation of cancer risk associated with a medication. PMID:24466131

  9. 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 estimate...... of the       5-year overall survival rate following radiotherapy is approximately 35%       in consecutive-selected patients and approximately 25% in       negative-selected patients...

  10. 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...... technologies emerging within proteomics. The purpose of this article is to briefly review what has been achieved to date using proteomic technologies and to bring forward novel strategies - based on the analysis of clinically relevant samples - that promise to accelerate the translation of basic discoveries...

  11. Intensity modulated radiotherapy for elderly bladder cancer patients

    International Nuclear Information System (INIS)

    To review our experience and evaluate treatment planning using intensity-modulated radiotherapy (IMRT) and helical tomotherapy (HT) for the treatment of elderly patients with bladder cancer. From November 2006 through November 2009, we enrolled 19 elderly patients with histologically confirmed bladder cancer, 9 in the IMRT and 10 in the HT group. The patients received 64.8 Gy to the bladder with or without concurrent chemotherapy. Conventional 4-field 'box' pelvic radiation therapy (2DRT) plans were generated for comparison. The median patient age was 80 years old (range, 65-90 years old). The median survival was 21 months (5 to 26 months). The actuarial 2-year overall survival (OS) for the IMRT vs. the HT group was 26.3% vs .37.5%, respectively; the corresponding values for disease-free survival were 58.3% vs. 83.3%, respectively; for locoregional progression-free survival (LRPFS), the values were 87.5% vs. 83.3%, respectively; and for metastases-free survival, the values were 66.7% vs. 60.0%, respectively. The 2-year OS rates for T1, 2 vs. T3, 4 were 66.7% vs. 35.4%, respectively (p = 0.046). The 2-year OS rate was poor for those whose RT completion time greater than 8 weeks when compared with the RT completed within 8 wks (37.9% vs. 0%, p = 0.004). IMRT and HT provide good LRPFS with tolerable toxicity for elderly patients with invasive bladder cancer. IMRT and HT dosimetry and organ sparing capability were superior to that of 2DRT, and HT provides better sparing ability than IMRT. The T category and the RT completion time influence OS rate

  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

    : The correlation between the relative bladder volume (RBV, defined as repeat scan volume/planning scan volume) and the margins required to account for internal motion was first studied using a series of 20 bladder cancer patients with weekly repeat CT scanning during treatment. Both conformal RT (CRT) and IGRT......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...... these patients were given fluid intake restrictions on alternating weeks during treatment. RESULTS: IGRT gave the strongest correlation between the RBV and margin size (R(2)=0.75; p10mm were required in only 1% of the situations when the RBV1, whereas isotropic margins >10...

  13. 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.

  14. Bladder filling variations during concurrent chemotherapy and pelvic radiotherapy in rectal cancer patients: early experience of bladder volume assessment using ultrasound scanner

    International Nuclear Information System (INIS)

    To describe the early experience of analyzing variations and time trends in bladder volume of the rectal cancer patients who received bladder ultrasound scan. We identified 20 consecutive rectal cancer patients who received whole pelvic radiotherapy (RT) and bladder ultrasound scan between February and April 2012. Before simulation and during the entire course of treatment, patients were scanned with portable automated ultrasonic bladder scanner, 5 times consecutively, and the median value was reported. Then a radiation oncologist contoured the bladder inner wall shown on simulation computed tomography (CT) and calculated its volume. Before simulation, the median bladder volume measured using simulation CT and bladder ultrasound scan was 427 mL (range, 74 to 1,172 mL) and 417 mL (range, 147 to 1,245 mL), respectively. There was strong linear correlation (R = 0.93, p < 0.001) between the two results. During the course of treatment, there were wide variations in the bladder volume and every time, measurements were below the baseline with statistical significance (12/16). At 6 weeks after RT, the median volume was reduced by 59.3% to 175 mL. Compared to the baseline, bladder volume was reduced by 38% or 161 mL on average every week for 6 weeks. To our knowledge, this study is the first to prove that there are bladder volume variations and a reduction in bladder volume in rectal cancer patients. Moreover, our results will serve as the basis for implementation of bladder training to patients receiving RT with full bladder.

  15. 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.

  16. 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

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

    Science.gov (United States)

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

    2012-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Jasmina Makarević

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

  19. 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.

  20. 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.

  1. 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.

  2. PIXE analysis of cancer-afflicted human bladder

    Energy Technology Data Exchange (ETDEWEB)

    Raju, G.J. Naga; Sarita, P.; Kumar, M. Ravi [Department of Physics, Institute of Technology, GITAM University, Visakhapatnam (India); Reddy, S. Bhuloka [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam (India)

    2013-07-01

    Full text: The proton induced x-ray emission (PIXE) technique was used for analysis of trace elements in small quantities of biological samples. Both the biological samples of normal and cancer-afflicted human bladder tissues were studied. The present experiment was performed using a 3 MV pelletron accelerator at the Institute of Physics in Bhubaneswar, India. A proton beam of 3 MeV energy was used to excite the samples. NIST SRM 1577b Bovine Liver Tissue was used as external standards for the determination of trace element concentration in the biological tissue samples. The elements CI, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, and Se were identified and their concentrations were estimated. The concentrations of Ti and Zn are lower (p < 0.005) and that of Cr, Mn, Fe, Ni, and Cu are significantly higher (p < 0.001) in cancerous tissues than that in normal tissues. The deficiency or excess of different trace elements observed in the cancer tissues relative to the normal tissues of bladder are correlated to the pathology of cancer. (author)

  3. PIXE analysis of cancer-afflicted human bladder

    International Nuclear Information System (INIS)

    Full text: The proton induced x-ray emission (PIXE) technique was used for analysis of trace elements in small quantities of biological samples. Both the biological samples of normal and cancer-afflicted human bladder tissues were studied. The present experiment was performed using a 3 MV pelletron accelerator at the Institute of Physics in Bhubaneswar, India. A proton beam of 3 MeV energy was used to excite the samples. NIST SRM 1577b Bovine Liver Tissue was used as external standards for the determination of trace element concentration in the biological tissue samples. The elements CI, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, and Se were identified and their concentrations were estimated. The concentrations of Ti and Zn are lower (p < 0.005) and that of Cr, Mn, Fe, Ni, and Cu are significantly higher (p < 0.001) in cancerous tissues than that in normal tissues. The deficiency or excess of different trace elements observed in the cancer tissues relative to the normal tissues of bladder are correlated to the pathology of cancer. (author)

  4. 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

  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. 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.

  7. Telomerase reverse transcriptase promoter mutations in bladder cancer

    DEFF Research Database (Denmark)

    Allory, Yves; Beukers, Willemien; Sagrera, Ana;

    2014-01-01

    for detection of recurrences in urine in patients with urothelial bladder cancer (UBC). DESIGN, SETTING, AND PARTICIPANTS: A set of 111 UBCs of different stages was used to assess TERT promoter mutations by Sanger sequencing and TERT messenger RNA (mRNA) expression by reverse transcription...... surveillance after diagnosis of non-muscle-invasive UBC (n=194), was tested using a SNaPshot assay. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Association of mutation status with age, sex, tobacco, stage, grade, fibroblast growth factor receptor 3 (FGFR3) mutation, progression-free survival, disease...

  8. Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer

    International Nuclear Information System (INIS)

    Treatment of patients with stage pT1 urothelial bladder cancer (UBC) continues to be a challenge due to its unpredictable clinical course. Reliable molecular markers that help to determine appropriate individual treatment are still lacking. Loss of aquaporin (AQP) 3 protein expression has previously been shown in muscle-invasive UBC. The aim of the present study was to investigate the prognostic value of AQP3 protein expression with regard to the prognosis of stage pT1 UBC. AQP 3 protein expression was investigated by immunohistochemistry in specimens of 87 stage T1 UBC patients, who were diagnosed by transurethral resection of the bladder (TURB) and subsequent second resection at a high-volume urological centre between 2002 and 2009. Patients underwent adjuvant instillation therapy with Bacillus Calmette-Guérin (BCG). Loss of AQP3 protein expression was defined as complete absence of the protein within the whole tumour. Expression status was correlated retrospectively with clinicopathological and follow-up data (median: 31 months). Multivariate Cox regression analysis was used to assess the value of AQP3 tumour expression with regard to recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS). RFS, PFS and CSS were calculated by Kaplan-Meier analysis and Log rank test. 59% of patients were shown to exhibit AQP3-positive tumours, whereas 41% of tumours did not express the marker. Loss of AQP3 protein expression was associated with a statistically significantly worse PFS (20% vs. 72%, p=0.020). This finding was confirmed by multivariate Cox regression analysis (HR 7.58, CI 1.29 – 44.68; p=0.025). Loss of AQP3 protein expression in pT1 UBC appears to play a key role in disease progression and is associated with worse PFS. Considering its potential prognostic value, assessment of AQP3 protein expression could be used to help stratify the behavior of patients with pT1 UBC

  9. 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.

  10. High-risk nonmuscle invasive bladder cancer: Definition and epidemiology

    OpenAIRE

    Porten, SP; Cooperberg, MR

    2012-01-01

    PURPOSE OF REVIEW: Nonmuscle invasive bladder cancer represents a large majority of patients diagnosed with this disease. Precise definition and risk stratification are paramount in this group as high-risk patients have higher rates of progression and mortality and may benefit from early identification and aggressive treatment. RECENT FINDINGS: The mainstay definitions of high-risk nonmuscle invasive bladder cancer are based on grade and stage. Recently, efforts have been made to incorporate ...

  11. Human Insulin Does Not Increase Bladder Cancer Risk

    OpenAIRE

    Chin-Hsiao Tseng

    2014-01-01

    BACKGROUND: Whether human insulin can induce bladder cancer is rarely studied. METHODS: The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 785,234 patients with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Users of pioglitazone were excluded and the period since the initiation of insulin glargine (marketed after the ent...

  12. Nonmuscle invasive bladder cancer: a primer on immunotherapy

    Science.gov (United States)

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

    2016-01-01

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

  13. Virtual 3D bladder reconstruction for augmented medical records from white light cystoscopy (Conference Presentation)

    Science.gov (United States)

    Lurie, Kristen L.; Zlatev, Dimitar V.; Angst, Roland; Liao, Joseph C.; Ellerbee, Audrey K.

    2016-02-01

    Bladder cancer has a high recurrence rate that necessitates lifelong surveillance to detect mucosal lesions. Examination with white light cystoscopy (WLC), the standard of care, is inherently subjective and data storage limited to clinical notes, diagrams, and still images. A visual history of the bladder wall can enhance clinical and surgical management. To address this clinical need, we developed a tool to transform in vivo WLC videos into virtual 3-dimensional (3D) bladder models using advanced computer vision techniques. WLC videos from rigid cystoscopies (1280 x 720 pixels) were recorded at 30 Hz followed by immediate camera calibration to control for image distortions. Video data were fed into an automated structure-from-motion algorithm that generated a 3D point cloud followed by a 3D mesh to approximate the bladder surface. The highest quality cystoscopic images were projected onto the approximated bladder surface to generate a virtual 3D bladder reconstruction. In intraoperative WLC videos from 36 patients undergoing transurethral resection of suspected bladder tumors, optimal reconstruction was achieved from frames depicting well-focused vasculature, when the bladder was maintained at constant volume with minimal debris, and when regions of the bladder wall were imaged multiple times. A significant innovation of this work is the ability to perform the reconstruction using video from a clinical procedure collected with standard equipment, thereby facilitating rapid clinical translation, application to other forms of endoscopy and new opportunities for longitudinal studies of cancer recurrence.

  14. Bladder Preservation by Combined Modality Therapy for Invasive Bladder Cancer: A Five-Year Follow-up

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jae Ho; Lim, Ji Hoon; Seong, Jin Sil; Pyo, Hong Ryull; Koom, Woong Soup; Suh, Chang Ok; Hong, Sung Jun [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2001-12-15

    Purpose : To determine the long-term results of bladder-preserving approach by transurethral resection of the bladder (TURB), systemic chemotherapy, and radiation therapy for muscle-invasive bladder cancer Methods and materials : From 1991 Jan, through 1994 Dec., 25 patients with muscle invading clinical stage T2 to T4NxM0 bladder cancer were treated width induction by maximal TURB and (arm 1, n=4) three cycles of chemotherapy [MVAC(methotrexate, vincristine, adriamycin, ciplatin)] followed by 64.8 Gy of radiation with concomitant cisplatin, or two cycles of chemotherapy [MCV (methotrexate, ciplatin, vincristine)] after irradiation with concomitant cisplatin (arm 2, n=14), or concurrent chemoradiation only (arm 3, n=7). Tumor response was scored as a clinical complete response (CR) when the cystoscopic tumor-site biopsy and urine cytology results were negative. Those with less than a CR underwent cystectomy. The median follow-up of al patients was 70 months. Results : Most treatment toxicities were mild to moderate. Grade 3 acute hematologic toxicity and chronic cystitis were observed in only 1 and 2 patients, respectively. Overall 5 year survival was 67.3%. Complete remission rate was 80% (20/25). Sixth-three percent of all survivors retained their bladders. In multivariate analysis, prognostic factors that significantly affect survival were T-stage (p=0.013) and Complete remission (p=0.002). Conclusion : Combined modality therapy with TURB, chemotherapy, and radiation has a 67.3% overall 5 year survival rate. This result is similar to cystectomy-based studies for patients of similar clinical stages. Sixty-three percent of long term survivors preserved their bladders.

  15. Bladder Preservation by Combined Modality Therapy for Invasive Bladder Cancer: A Five-Year Follow-up

    International Nuclear Information System (INIS)

    Purpose : To determine the long-term results of bladder-preserving approach by transurethral resection of the bladder (TURB), systemic chemotherapy, and radiation therapy for muscle-invasive bladder cancer Methods and materials : From 1991 Jan, through 1994 Dec., 25 patients with muscle invading clinical stage T2 to T4NxM0 bladder cancer were treated width induction by maximal TURB and (arm 1, n=4) three cycles of chemotherapy [MVAC(methotrexate, vincristine, adriamycin, ciplatin)] followed by 64.8 Gy of radiation with concomitant cisplatin, or two cycles of chemotherapy [MCV (methotrexate, ciplatin, vincristine)] after irradiation with concomitant cisplatin (arm 2, n=14), or concurrent chemoradiation only (arm 3, n=7). Tumor response was scored as a clinical complete response (CR) when the cystoscopic tumor-site biopsy and urine cytology results were negative. Those with less than a CR underwent cystectomy. The median follow-up of al patients was 70 months. Results : Most treatment toxicities were mild to moderate. Grade 3 acute hematologic toxicity and chronic cystitis were observed in only 1 and 2 patients, respectively. Overall 5 year survival was 67.3%. Complete remission rate was 80% (20/25). Sixth-three percent of all survivors retained their bladders. In multivariate analysis, prognostic factors that significantly affect survival were T-stage (p=0.013) and Complete remission (p=0.002). Conclusion : Combined modality therapy with TURB, chemotherapy, and radiation has a 67.3% overall 5 year survival rate. This result is similar to cystectomy-based studies for patients of similar clinical stages. Sixty-three percent of long term survivors preserved their bladders

  16. URODYNAMIC FINDINGS IN ASSESSMENT OF THE RESULTS OF PARTIAL CYSTECTOMY FOR BLADDER CANCER

    OpenAIRE

    F. Sh. Engalychev; N.G. Galkina

    2014-01-01

    Objectives. We determined the role of urodynamic results on the estimation of treatment efficiency of patients with bladder cancer.Subjects and methods. The study consequently included 160 patients receiving TUR and open resection in 2005−2009. Quality of life was assessed using the IPSS, QoL and International Inventory of Erectile Function (IIEF). Uroflowmetry, bladder diary were carried out to determine lower urinary tract symptoms befor treatment, 3 and 12 mo later.Results. In 3 months aft...

  17. Lymphatic vessel density and function in experimental bladder cancer

    International Nuclear Information System (INIS)

    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. 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. SV40-lacZ mice develop bladder cancer and permitted visualization of lymphatics. A significant increase in LVD was found concomitantly with bladder cancer progression. Double labeling of the bladder cross-sections with LYVE-1 and Ki-67 antibodies indicated cancer-induced lymphangiogenesis. MRI detected mouse bladder cancer, as early as 4 months, and permitted to follow tumor sizes during cancer progression. Using Gd-Cy5.5 as a contrast agent for MRI-guided lymphangiography, we determined a possible reduction of lymphatic flow within the tumoral area. In addition, NIRF

  18. 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

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

    Science.gov (United States)

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

    2012-12-01

    The aim of this study is to develop a novel semiautomatic bladder segmentation approach for selecting the appropriate plan from the library of plans for a multiple-plan adaptive radiotherapy (ART) procedure. A population-based statistical bladder model was first built from a training data set (95 bladder contours from 8 patients). This model was then used as constraint to segment the bladder in an independent validation data set (233 CBCT scans from the remaining 22 patients). All 3D bladder contours were converted into parametric surface representations using spherical harmonic expansion. Principal component analysis (PCA) was applied in the spherical harmonic-based shape parameter space to calculate the major variation of bladder shapes. The number of dominating PCA modes was chosen such that 95% of the total shape variation of the training data set was described. The automatic segmentation started from the bladder contour of the planning CT of each patient, which was modified by changing the weight of each PCA mode. As a result, the segmentation contour was deformed consistently with the training set to best fit the bladder boundary in the localization CBCT image. A cost function was defined to measure the goodness of fit of the segmentation on the localization CBCT image. The segmentation was obtained by minimizing this cost function using a simplex optimizer. After automatic segmentation, a fast manual correction method was provided to correct those bladders (parts) that were poorly segmented. Volume- and distance-based metrics and the accuracy of plan selection from multiple plans were evaluated to quantify the performance of the automatic and semiautomatic segmentation methods. For the training data set, only seven PCA modes were needed to represent 95% of the bladder shape variation. The mean CI overlap and residual error (SD) of automatic bladder segmentation over all of the validation data were 70.5% and 0.39 cm, respectively. The agreement of plan

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  2. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  3. The Molecular Pathogenesis of Bladder Cancer

    NARCIS (Netherlands)

    A.G. van Tilborg (Angela)

    2001-01-01

    textabstractThe bladder is a hollow organ in the small pelvis. It stores urine that is produced when the kidneys filter the blood. Four different layers, the epithelium, lamina propria, muscularis, and connective tissue, define the bladder wall. The epithelium consists of 7 to 10 cell layers and res

  4. Intra-arterial chemotherapy for invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ozono, Seiichiro; Kim, Sung-Chul; Takashima, Kenji [Nara Medical Univ., Kashihara (Japan)] [and others

    1999-02-01

    The present investigation was conducted to examine the effects of intra-arterial chemotherapy (IAC) for patients with invasive bladder cancer. A total of 37 patients were treated with IAC at Nara Medical University and its affiliated hospitals between January, 1993 and August, 1997. There were 27 patients in the poor risk group. The remaining 10 patients underwent anti-tumor IAC. Thirty of the 37 patients received chemotherapeutic agents via a reservoir, and the remaining 7 patients received a one-shot injection of agents followed by transcatheter arterial embolization (TAE). In the reservoir group, there were 18 patients who received IAC in combination with radiation therapy. As a result, reduction of tumor size was noted in 53%, and the 3-year cause-specific survival rate was 54% in all cases. There was a significant difference in the 3-year survival rate between the radiation-treated group and the group without radiation. The adverse events included anemia, leukopenia, thrombocytopenia and gastrointestinal symptoms, but none of them were severe. The results of the present study indicate that IAC is useful in the treatment of invasive bladder cancer for poor risk patients. (author)

  5. Intra-arterial chemotherapy for invasive bladder cancer

    International Nuclear Information System (INIS)

    The present investigation was conducted to examine the effects of intra-arterial chemotherapy (IAC) for patients with invasive bladder cancer. A total of 37 patients were treated with IAC at Nara Medical University and its affiliated hospitals between January, 1993 and August, 1997. There were 27 patients in the poor risk group. The remaining 10 patients underwent anti-tumor IAC. Thirty of the 37 patients received chemotherapeutic agents via a reservoir, and the remaining 7 patients received a one-shot injection of agents followed by transcatheter arterial embolization (TAE). In the reservoir group, there were 18 patients who received IAC in combination with radiation therapy. As a result, reduction of tumor size was noted in 53%, and the 3-year cause-specific survival rate was 54% in all cases. There was a significant difference in the 3-year survival rate between the radiation-treated group and the group without radiation. The adverse events included anemia, leukopenia, thrombocytopenia and gastrointestinal symptoms, but none of them were severe. The results of the present study indicate that IAC is useful in the treatment of invasive bladder cancer for poor risk patients. (author)

  6. 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.

  7. 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.

  8. Stage of urinary bladder cancer at first presentation

    Directory of Open Access Journals (Sweden)

    Al-Bazzaz Pishtewan

    2009-01-01

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

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

    International Nuclear Information System (INIS)

    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. 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. CDH1 and SFN genes were methylated at high frequencies in bladder cancer as well as in paired normal adjacent tissue and exfoliated cells from cancer-free patients. Although no statistically significant differences were found between RARB and RASSF1A methylation and the clinical and histopathological parameters in bladder cancer, a sensitivity of 95% and a specificity of 71% were observed for RARB methylation (Fisher's Exact test (p < 0.0001; OR = 48.89) and, 58% and 17% (p < 0.05; OR = 0.29) for RASSF1A gene, respectively, in relation to the control group. 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

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

    Science.gov (United States)

    2012-01-01

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

  11. 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

  12. Contemporary management of muscle-invasive bladder cancer

    OpenAIRE

    Dall’Era, Marc A; Cheng, Liang; Pan, Chong-xian

    2012-01-01

    The current standard treatment for muscle-invasive nonmetastatic bladder cancer is neoadjuvant platinum-based chemotherapy followed by radical cystectomy. However, neoadjuvant chemotherapy is not widely accepted even with level 1 evidence. Adjuvant chemotherapy should be discussed if patients have not received neoadjuvant chemotherapy before surgery and have high-risk pathologic features. Although not considered standard of care, bladder-sparing therapy can be considered for highly selected p...

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Ganglong Yang

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

  15. [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.

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

    Science.gov (United States)

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

    2010-07-21

    We previously investigated bladder cancer risk in a cohort of dyestuff workers who were heavily exposed to aromatic amines from 1922 through 1972. We updated the follow-up by 14 years (through 2003) for 590 exposed workers to include more than 30 years of follow-up since last exposure to aromatic amines. Expected numbers of deaths from bladder cancer and other causes were computed by use of national mortality rates from 1951 to 1980 and regional mortality rates subsequently. There were 394 deaths, compared with 262.7 expected (standardized mortality ratio = 1.50, 95% confidence interval = 1.36 to 1.66). Overall, 56 deaths from bladder cancer were observed, compared with 3.4 expected (standardized mortality ratio = 16.5, 95% confidence interval = 12.4 to 21.4). The standardized mortality ratio for bladder cancer increased with younger age at first exposure and increasing duration of exposure. Although the standardized mortality ratio for bladder cancer steadily decreased with time since exposure stopped, the absolute risk remained approximately constant at 3.5 deaths per 1000 man-years up to 29 years after exposure stopped. Excess risk was apparent 30 years or more after last exposure. PMID:20548022

  17. 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....

  18. 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.

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

    OpenAIRE

    Goossens, Maria E; Isa, Fatima; Brinkman, Maree; Mak, David; Reulen, Raoul; Wesselius, Anke; Benhamou, Simone; Bosetti, Cristina; Bueno-De-Mesquita, Bas; Carta, Angela; Allam, Md Farouk; Golka, Klaus; Grant, Eric J; Jiang, Xuejuan; Johnson, Kenneth C.

    2016-01-01

    Background In 2012, more than 400,000 urinary bladder cancer cases occurred worldwide, making it the 7th most common type of cancer. Although many previous studies focused on the relationship between diet and bladder cancer, the evidence related to specific food items or nutrients that could be involved in the development of bladder cancer remains inconclusive. Dietary components can either be, or be activated into, potential carcinogens through metabolism, or act to prevent carcinogen damage...

  20. Contemporary management of muscle-invasive bladder cancer

    Science.gov (United States)

    Dall’Era, Marc A; Cheng, Liang; Pan, Chong-Xian

    2012-01-01

    The current standard treatment for muscle-invasive nonmetastatic bladder cancer is neoadjuvant platinum-based chemotherapy followed by radical cystectomy. However, neoadjuvant chemotherapy is not widely accepted even with level 1 evidence. Adjuvant chemotherapy should be discussed if patients have not received neoadjuvant chemotherapy before surgery and have high-risk pathologic features. Although not considered standard of care, bladder-sparing therapy can be considered for highly selected patients and for those medically unfit for surgery. Even though there are no level 1 data, the treatment outcomes for highly select patients given bladder-sparing therapy appear promising, with many patients retaining a functional bladder. Personalized chemotherapy is currently being actively pursued to target the underlying molecular changes and tailor to individual needs. PMID:22845409

  1. Optimizing the diagnosis and treatment of bladder cancer using fluorescence cystoscopy and Raman spectroscopy

    NARCIS (Netherlands)

    Draga, R.O.P.

    2013-01-01

    The gold standard for the diagnosis and treatment of bladder cancer is transurethral resection of bladder tumors (TURBT). A relative high recurrence rate and the need for repeated treatments make bladder cancer one the most expensive cancers from diagnosis till death of the patient. The TURBT accoun

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

    Science.gov (United States)

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

    2016-02-01

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

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

    Directory of Open Access Journals (Sweden)

    T. Salman

    1996-01-01

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

  4. Preliminary assessment of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with bladder cancer

    International Nuclear Information System (INIS)

    The purpose of this study was to assess the feasibility of imaging of bladder cancer with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scanning. We studied 12 patients with histologically proven bladder cancer who had undergone surgical procedures and/or radiotherapy. Retrograde irrigation of the urinary bladder with 1000-3710 ml saline was performed during nine of the studies. Dynamic and static PET images were obtained, and standardized uptake value images were reconstructed. FDG-PET scanning was true-positive in eight patients (66.7%), but false-negative in four (33.3%). Of 20 organs with tumor mass lesions confirmed pathologically or clinically, 16 (80%) were detected by FDG-PET scanning. FDG-PET scanning detected all of 17 distant metastatic lesions and two of three proven regional lymph node metastases. FDG-PET was also capable of differentiating viable recurrent bladder cancer from radiation-induced alterations in two patients. In conclusion, these preliminary data indicate the feasibility of FDG-PET imaging in patients with bladder cancer, although a major remaining pitfall is intense FDG accumulation in the urine. (orig.). With 3 figs., 1 tab

  5. Functional polymorphisms in the matrix metalloproteinase genes and their association with bladder cancer risk and recurrence: a mini-review.

    Science.gov (United States)

    Wieczorek, Edyta; Wasowicz, Wojciech; Gromadzinska, Jolanta; Reszka, Edyta

    2014-08-01

    Molecular pathogenesis of muscle invasive bladder cancer and non-muscle invasive bladder cancer is incompletely elucidated. It is believed that matrix metalloproteinases, which are involved in the processes of uncontrolled extracellular matrix substrates degradation and participate in modulating the activity of a variety of non-matrix proteins, can contribute to carcinogenesis. Polymorphisms in the MMP genes associated with unique genomic changes in bladder cancer patients are still being investigated to discover direct links with pathophysiological mechanisms. Because of the functional polymorphisms in the MMP genes, which have a proven or likely effect on their protein expression, they could possibly affect the tumor process. The current mini-review synthesizes findings regarding the association of genetic polymorphisms in the MMP genes with bladder cancer risk and recurrence in patients. We discuss the current views on the feasibility of genetic polymorphisms in the MMP1, 2, 3, 7, 8, 9 and 12 genes as a risk, and prognostic markers for patients with bladder cancer. The majority of the research described in the present mini-review proves that the genetic polymorphism in the MMP1 (rs1799750) is the most widely studied, and suggests that the rare genotype, 2G2G, of that gene might show increased susceptibility for bladder cancer, especially among smokers. However, existing statistically significant associations between the genetic polymorphisms in the MMP genes and bladder cancer risk have not been clearly shown, and further studies are necessary in order to positively confirm them or dispel potential false hopes. PMID:24635493

  6. 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 !

  7. 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

  8. Poly(I:C) potentiates Bacillus Calmette-Guérin immunotherapy for bladder cancer.

    Science.gov (United States)

    Ayari, Cherifa; Besançon, Marjorie; Bergeron, Alain; LaRue, Hélène; Bussières, Vanessa; Fradet, Yves

    2016-02-01

    Non-specific immunotherapy consisting of intravesical instillation of Bacillus Calmette-Guérin (BCG) is currently the best available treatment to prevent non-muscle-invasive bladder tumor recurrence and progression. This treatment however is suboptimal, and more effective immunotherapeutic approaches are needed. Toll-like receptors (TLRs) play a major role in the activation of the immune system in response to pathogens and danger signals but also in anti-tumor responses. We previously showed that human urothelial cells express functional TLRs and respond to TLR2 and TLR3 agonists. In this study, we analyzed the potential of polyinosinic:polycytidylic acid [poly(I:C)], a TLR3 agonist, to replace or complement BCG in the treatment of non-muscle-invasive bladder cancer. We observed that poly(I:C) had an anti-proliferative, cytotoxic, and apoptotic effect in vitro on two low-grade human bladder cancer cell lines, MGH-U3 and RT4. In MGH-U3 cells, poly(I:C) induced growth arrest at the G1-S transition. Poly(I:C) also increased the immunogenicity of MGH-U3 and RT4 cells, inducing the secretion of MHC class I molecules and of pro-inflammatory cytokines. By comparison, poly(I:C) had less in vitro impact on two high-grade human bladder cancer cell lines, 5637 and T24, and on MBT-2 murine high-grade bladder cancer cells. The latter can be used as an immunocompetent model of bladder cancer. The combination poly(I:C)/BCG was much more effective in reducing MBT-2 tumor growth in mice than either treatment alone. It completely cured 29% of mice and also induced an immunological memory response. In conclusion, our study suggests that adding poly(I:C) to BCG may enhance the therapeutic effect of BCG. PMID:26759009

  9. Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer

    OpenAIRE

    Nogawa, Masaki; Yuasa, Takeshi; Kimura, Shinya; Tanaka, Motoyoshi; Kuroda, Junya; SATO, Kiyoshi; Yokota, Asumi; Segawa, Hidekazu; Toda, Yoshinobu; Kageyama, Susumu; YOSHIKI, Tatsuhiro; Okada, Yusaku; Maekawa, Taira

    2005-01-01

    The mainstay in the management of invasive bladder cancer continues to be radical cystectomy. With regard to improvement of quality of life, however, therapies that preserve the bladder are desirable. We investigated the use of intravesical PLK-1 small interfering RNA (siRNA) against bladder cancer. Patients with bladder cancers expressing high levels of PLK-1 have a poor prognosis compared with patients with low expression. Using siRNA/cationic liposomes, the expression of endogenous PLK-1 c...

  10. 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.

  11. 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

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

    Science.gov (United States)

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

    2013-01-01

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

  13. 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.

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

    Science.gov (United States)

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

    2016-07-28

    In an effort to improve local bladder cancer control, we investigated the cytotoxic and genotoxic effects of quercetin on human bladder cancer T24 cells. The cytotoxic effect of quercetin against T24 cells was examined by MTT test, clonogenic assay as well as DNA damaging effect by comet assay. In addition, the cytotoxic effect of quercetin on the primary culture of papillary urothelial carcinoma (PUC), histopathological stage T1 of low- or high-grade tumours, was investigated. Our analysis demonstrated a high correlation between reduced number of colony and cell viability and an increase in DNA damage of T24 cells incubated with quercetin at doses of 1 and 50 µM during short term incubation (2 h). At all exposure times (24, 48 and 72 h), the efficacy of quercetin, administered at a 10× higher dose compared to T24 cells, was statistically significant (P < 0.05) for the primary culture of PUC. In conclusion, our study suggests that quercetin could inhibit cell proliferation and colony formation of human bladder cancer cells by inducing DNA damage and that quercetin may be an effective chemopreventive and chemotherapeutic agent for papillary urothelial bladder cancer after transurethral resection. PMID:27149655

  15. INTRAVESICAL BCG THERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER

    OpenAIRE

    K. M. Figurin

    2014-01-01

    The paper considers the state-of-the-art of BCG vaccine treatment for non-muscle invasive bladder cancer. It gives data on the meta-analyses of foreign studies of the efficiency of BCG therapy in this pathology.

  16. 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...

  17. Molecular markers for detection, surveillance and prognostication of bladder cancer.

    NARCIS (Netherlands)

    Vrooman, O.P.; Witjes, J.A.

    2009-01-01

    Many markers for the detection of bladder cancers have been tested and almost all urinary markers reported are better than cytology with regard to sensitivity, but they score lower in specificity. Currently molecular and genetic changes play an important role in the discovery of new molecular marker

  18. 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

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

    Directory of Open Access Journals (Sweden)

    Carmen J Marsit

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

  20. 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.

  1. 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.

  2. 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.

  3. The role of microRNAs in bladder cancer

    OpenAIRE

    ENOKIDA, HIDEKI; YOSHINO, HIROFUMI; Matsushita, Ryosuke; Nakagawa, Masayuki

    2016-01-01

    Bladder cancer (BC) is the fifth most common cancer worldwide and is associated with significant morbidity and mortality. The prognosis of muscle invasive BC is poor, and recurrence is common after radical surgery or chemotherapy. Therefore, new diagnostic methods and treatment modalities are critical. MicroRNAs (miRNAs), a class of small noncoding RNAs, regulate the expression of protein-coding genes by repressing translation or cleaving RNA transcripts in a sequence-specific manner. miRNAs ...

  4. Quality of life in urinary bladder and prostate cancer patients

    OpenAIRE

    Schmidt, Stefanie

    2014-01-01

    The overall objective of this thesis was to describe the evolution of Health-Related Quality of Life in Spanish patients with urologic tumours; and to the examine clinical and treatment-related factors associated with changes in Health-Related Quality of Life during the first year of treatment. The EMPARO project is an observational, multicenter, prospective study on patients diagnosed with bladder cancer (n=326) and prostate cancer (n=472). Consecutive patients were enrolled in 7 Spanish hos...

  5. 膀胱癌膀胱全切术ICD-9-CM-3编码研究%ICD-9-CM-3 Coding Research of Bladder Cancer noma Radical Cystectomy

    Institute of Scientific and Technical Information of China (English)

    范炜然; 王建玥; 张磊; 林海丽

    2011-01-01

    目的 探讨膀胱癌膀胱全切术及尿流改道术ICD-9-CM-3分类编码.方法 总结临床常用的膀胱癌膀胱全切术及尿流改道术的手术方式,根据(ICD-9-CM-3(2008版)对所做手术进行编码.结论 疾病分类的工作人员应熟练掌握手术操作编码的原则,同时应了解各种手术的方法,仔细阅读手术记录,经常与临床医师沟通以求准确编码,以满足临床医教研和职能部门的统计需要.%Objective to discuss ICD-9-CM-3 classification coding of bladder cancer noma radical cystectomy and urinary division. Methods a summary on clinical common bladder cancer noma radical cystectomy and urinary division operation mode, according to No. Ninth Clinical Revised Edition Surgery and Operation of International Diseases Classification (ICD-9-CM-3 2008 edition), to code operation. Conclusions disease classification staffs should know well about the principle of operation coding and ways of operation, who should read carefully about operation records and communicate with clinical doctors for correct coding in order to satisfy the statistical requirement of clinical teaching and research and function departments.

  6. 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

  7. A RETROSPECTIVE STUDY OF THE EFFICACY OF CHEMOIRRADIATION IN LOCALLY ADVANCED URINARY BLADDER CANCER

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    Nehru

    2015-04-01

    Full Text Available BACKGROUND : Radical cystectomy with pelvic lymph node dissection is the standard method used to treat patients with locally advanced carcinoma of urinary bladder. Furthermore, a significant proportion of patients are deemed unsuitable for surgery due to inoperability, advanced age, and/or comorbid conditions. B ecause of disappointing results with radical cystectomy in terms of survival, as well as the morbidity and decreased quality of life associated with the surgery, bladder - conserving therapies like trimodality (TURBT, concurrent chemoradiation therapy have been gained popularity as the survival rates are nearly equal with radical cystectomy along with functioning bladder. AIM OF STUDY : To study retrospectively the effectiveness of chemoradition therapy in bladder preservation approach in the management of p atients with locally advanced ( I nvasive bladder cancer in medically unfit and unwilling patients for radical cystectomy and those who cannot tolerate combination chemotherapy drugs. METHOD S AND MATERIAL : The data was collected from the patient’s records between 2004 - 2010 who were treated in our Regional cancer hospital. All were biopsy/CT scan proven muscle invasive urinary bladder tumors with T2 – 3, N0, M0 lesions. Post TURBT status. Medi cally unfit and Unwillingness for surgery and underwent concurrent Radiotherapy with weekly cisplatin therapy. And men and / women with age between 45 - 70 years were included in the study. RESULTS : Out of 28 patients 4 (14.29% patients who had good TURP procedure showed complete response , 20(71.43% patients had partial response and 4(14.29% patients showed stable disease. 71.43% patient showed symptomatic response to treatment . CONCLUSION : Being a single agent chemotherapy with radiation and it is feasible without major toxicity and offers a potentially usefulness in locoregional control and symptomatic relief in unfavorable population with invasive bladder cancer. Moreover it

  8. 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...

  9. Complete transurethral bladder eversion 3 months after hemipelvectomy.

    Science.gov (United States)

    Lowe, Gregory; Mandalapu, Subbarao; Gilleran, Jason

    2010-02-01

    A 46-year-old white female underwent a left hemipelvectomy for chondrosarcoma. She presented with total incontinence and a bulging vaginal mass. Exam confirmed complete transurethral bladder eversion that was addressed with transvaginal multilayer bladder neck closure and suprapubic tube placement. Eventually she underwent abdominal hysterectomy, mesh sacral colpopexy, and catheterizable stoma creation. Patient is continent of urine 3 months postoperatively. We present the first reported case of bladder eversion after hemipelvectomy and propose possible pathophysiologic mechanisms. PMID:19629370

  10. Pirarubicin induces an autophagic cytoprotective response through suppression of the mammalian target of rapamycin signaling pathway in human bladder cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Kuiqing; Chen, Xu [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Liu, Cheng [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Gu, Peng; Li, Zhuohang; Wu, Shaoxu [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Xu, Kewei [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Lin, Tianxin, E-mail: tianxinl@sina.com [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Huang, Jian, E-mail: urolhj@sina.com [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China)

    2015-05-01

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

  11. Pirarubicin induces an autophagic cytoprotective response through suppression of the mammalian target of rapamycin signaling pathway in human bladder cancer cells

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Haifeng Zhang

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

  13. Natural history of pT3-4 or node positive bladder cancer treated with radical cystectomy and no neoadjuvant chemotherapy in a contemporary North-American multi-institutional cohort

    Science.gov (United States)

    Power, Nicholas E.; Kassouf, Wassim; Bell, David; Aprikian, Armen G.; Fradet, Yves; Lacombe, Louis; Chin, Joseph; Izawa, Jonathan; Estey, Eric; Fairey, Adrian; Cagiannos, Ilias; Lattouf, Jean-Baptiste; Drachenberg, Darrel; Rendon, Ricardo A.

    2012-01-01

    Background: The present study documents the natural history and outcomes of high-risk bladder cancer after radical cystectomy (RC) in patients who did not receive neoadjuvant chemotherapy during a contemporary time period. Methods: We analyzed 1180 patients from 1993 to 2008 with >pT3N0 or pT0-4N+ bladder cancer who underwent RC ± standard (sLND) or extended (eLND) lymph node dissection from 8 Canadian centres. Results: Of the 1180 patients, 55% (n = 643) underwent sLND, 34% (n = 402) underwent ePLND and 11% did not undergo a formal LND. Of the total number of patients, 321 (27%) received adjuvant chemotherapy. The median follow-up was 2.1 years (range: 0.6 to 12.9). Overall 30-day mortality was 3.2%. Clinical and pathological stages T3-4 were present in 6.1% and 86.7% of the patients, respectively; this demonstrates a dramatic understaging. Overall survival (OS) at 2 and 5 years was 60% and 43%, respectively. Patients who received adjuvant chemotherapy had a 2- and 5-year disease-specific survival (DSS) of 72% and 57% versus 64% and 51% for those who did not (log-rank p = 0.0039). The 2- and 5-year OS for high-risk node-negative disease was 67% and 52%, respectively, whereas for node-positive patients, the OS was 52% and 32%, respectively (p < 0.001). The OS, DSS and RFS for patients with pN0 were significantly improved compared to those who did not undergo a LND (log-rank p = 0.0035, 0.0241 and 0.0383, respectively). Interpretation: This series suggests that bladder cancer outcomes in advanced disease have improved in the modern era. The need for improved staging investigations, use of neoadjuvant chemotherapy and performance of complete LND is emphasized. PMID:23283097

  14. 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

  15. 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.

  16. 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.

  17. Genetic Polymorphisms of CYP2A6 in a Case-Control Study on Bladder Cancer in Japanese Smokers.

    Science.gov (United States)

    Kumondai, Masaki; Hosono, Hiroki; Orikasa, Kazuhiko; Arai, Yoichi; Arai, Tomio; Sugimura, Haruhiko; Ozono, Seiichiro; Sugiyama, Takayuki; Takayama, Tatsuya; Sasaki, Takamitsu; Hirasawa, Noriyasu; Hiratsuka, Masahiro

    2016-01-01

    Several of the procarcinogens inhaled in tobacco smoke, the primary risk factor for bladder cancer, are activated by CYP2A6. The association between the whole-gene deletion of CYP2A6 (CYP2A6*4) and a reduced risk of bladder cancer was suggested in Chinese Han smokers. However, there is no evidence for association between the risk of bladder cancer and CYP2A6 genotypes in the Japanese population. Using genomic DNA from smokers of the Japanese population (163 bladder cancer patients and 116 controls), we conducted a case-control study to assess the association between CYP2A6 polymorphisms and the risk of bladder cancer. Determination of CYP2A6 genotypes was carried out by amplifying each exon of CYP2A6 using polymerase chain reaction (PCR) and Sanger sequencing. The CYP2A6*4 allele was identified by an allele-specific PCR assay. Bladder cancer risk was evaluated using the activity score (AS) system based on CYP2A6 genotypes. The odds ratios (95% confidence interval) for the AS 0, AS 0.5, AS 1.0, and AS 1.5 groups were 0.46 (0.12-1.83), 0.43 (0.15-1.25), 0.86 (0.40-1.86), and 1.36 (0.60-3.06), respectively. In conclusion, although decreased CYP2A6 AS tended to reduce the risk of bladder cancer in Japanese smokers, no significant association was recognized in this population. However, given the relatively small size of the sample, further study is required to conclude the lack of a statistically significant association between CYP2A6 genotypes and the risk of bladder cancer. PMID:26725431

  18. 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.

  19. Activation of Nerve Growth Factor-Induced Bα by Methylene-Substituted Diindolylmethanes in Bladder Cancer Cells Induces Apoptosis and Inhibits Tumor GrowthS⃞

    OpenAIRE

    Dae Cho, Sung; Lee, Syng-Ook; Chintharlapalli, Sudhakar; Abdelrahim, Maen; Khan, Shaheen; Yoon, Kyungsil; Kamat, Ashish M.; Safe, Stephen

    2010-01-01

    Nerve growth factor-induced B (NGFI-B) genes are orphan nuclear receptors, and NGFI-Bα (Nur77, TR3) is overexpressed in bladder tumors and bladder cancer cells compared with nontumorous bladder tissue. 1,1-Bis(3′-indolyl)-1-(p-methoxyphenyl)-methane (DIM-C-pPhOCH3) and 1,1-bis(3′-indolyl)-1-(p-phenyl)methane have previously been identified as activators of Nur77, and both compound...

  20. Exosomal protein interactors as emerging therapeutic targets in urothelial bladder cancer

    International Nuclear Information System (INIS)

    Background: Exosomes are rich sources of biological material (proteins and nucleic acids) secreted by both tumor and normal cells, and found in urine of urinary bladder cancer patients. Objective: The objective of the study was to identify interacting exosomal proteins in bladder cancer for future use in targeted therapy. Methods: The Exocarta database (www.exocarta.org) was mined for urinary bladder cancer specific exosomal proteins. The urinary bladder cancer specific exosomal proteins (n = 248) were analyzed to identify enriched pathways by Onto-tool Pathway Express (http://vortex.cs.wayne.edu/ ontoexpress). Results: Enriched pathways included cellular architecture, motility, cell to cell adhesion, tumorigenesis and metastasis. Proteins in the 9 top-ranked pathways included CTNNA1 (alpha-catenin), CTNNB1 (beta-catenin), VSAP, ITGA4, PAK1, DDR1, CDC42, RHOA, NRAS, RHO, PIK3AR1, MLC1, MMRN1, and CTTNBP2 and network analysis revealed 10 important hub proteins and identified inferred interactor NF2. Conclusions: The importance of identifying interactors is that that they can be used as targets for therapy, for example, using Bevacizumab (avastin - an angiogenesis inhibitor) against NF2 to inhibit protein-protein interactions will inhibit tumor growth and progression by hindering the exosome biogenesis

  1. 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 (Pin vivo models of urinary bladder cancer. These findings support that meloxicam deserves more attention on urinary bladder cancer study.

  2. 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).

  3. 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.

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

    OpenAIRE

    Masayoshi Nagata; Satoru Muto; Shigeo Horie

    2016-01-01

    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 pr...

  5. 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.

  6. MOLECULAR GENETIC MARKERS AS PREDICTORS OF SUPERFICIAL BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    A. Yu. Babayan

    2009-01-01

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

  7. Trimodality bladder-sparing approach without neoadjuvant chemotherapy for node-negative localized muscle-invasive urinary bladder cancer resulted in comparable cystectomy-free survival

    International Nuclear Information System (INIS)

    To retrospectively review the efficacy and organ preservation experience for muscle-invasive bladder cancer by trimodality therapy at our institution. Between July 2004 and February 2012, seventy patients (M/F = 55/15; median age = 69 years) of lymph node negative localized muscle-invasive bladder cancer were treated primarily with trimodality approach including transurethral resection of bladder tumor (TURBT) prior to combined chemotherapy and radiotherapy (CCRT). Radiotherapy consisted of initial large field size irradiation with 3D conformal technique (3D-CRT), followed by cone-down tumor bed boost with intensity modulated radiotherapy (IMRT) technique. The median total doses delivered to bladder tumor bed and whole bladder were 59.4Gy and 40.0Gy, respectively. No patient received neoadjuvant chemotherapy (NAC). Weekly cisplatin was administered during radiotherapy. Toxicity was scored according to the RTOG criteria. Tumor response was evaluated both cystoscopically and radiographically 3 months after treatment. The numbers of patients with T2, T3 and T4 lesions were 41, 16 and 13, respectively. Overall survival (OS) and progression-free survival (PFS) at 2 and 5 year were 65.7%, 51.9% and 50.8%, 39.9%, respectively, after a median follow-up time of 24 months. Local-regional control and distant metastasis free survival at 2 year were 69.8% and 73.5%, respectively. Complete response (CR) rate assessed three month after CCRT was 78.1%. Ten patients (20%) had local recurrence after initial CR (n = 50), 3 of them were superficial recurrence. One patient underwent radical cystectomy after recurrence. The overall 5-year bladder intact survival was 49.0% (95% CI, 35.5% to 62.5%). Acute toxicities were limited to grade 1-2. One patient developed late grade 3 GU toxicity. Our result suggested that trimodality bladder-sparing approach without NAC or dose-intensification could be well-tolerated with a high CR rate and bladder preserving rate for muscle-invasive bladder

  8. Utility of CT during arteriography in superselective transarterial chemoembolization for invasive bladder cancer

    International Nuclear Information System (INIS)

    The aims of this study were to assess the effectiveness of CT during arteriography (CTA) in superselective transarterial chemoembolization (TACE) for invasive bladder cancer, and to report preliminary results of superselective TACE. Angiography was performed in 20 patients with invasive bladder cancer, using a combined CT-Angiography system. Of the 20 tumors, 19 were T3, one was T2. The vesical arteries were selected using a 3F microcatheter, and perfusion was confirmed using CTA. TACE was performed after administrating 40 to 100 mg of cisplatin, with and without gelatin sponge particles. The effects of TACE were assessed by surgery or a combination of cystoscopy and CT in 15 cases. The vesical arteries were successfully selected in 18 of 20 patients. In 16 small tumors, the tumor stain was clearly depicted on CTA. In two large tumors, the vascular supply was identified as involving multiple arteries. One case showed complete remission, six showed partial remission, and eight showed no change. Complications included mild local pain around the perineum during TACE, and transient nausea in some patients. CTA may be useful in superselective TACE for invasive bladder cancer, and may contribute to effective treatment of bladder tumors. (author)

  9. 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.

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

    OpenAIRE

    L. V. Mirylenka; O. G. Sukonko; A. V. Pravorov; A. I. Rolevich; A. S. Mavrichev

    2014-01-01

    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 nom...

  11. Kaempferol Promotes Apoptosis in Human Bladder Cancer Cells by Inducing the Tumor Suppressor, PTEN

    Directory of Open Access Journals (Sweden)

    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.

  12. 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).

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

    OpenAIRE

    Cheryl Shih; Porter, Michael P

    2011-01-01

    With multiple options for urinary diversion after radical cystectomy for bladder cancer that have comparable cancer control and complication rates, health-related quality of life (HRQOL) has become an important consideration. This article reviews the methods for defining HRQOL, the challenges in measuring HRQOL in bladder cancer, and the literature comparing HRQOL after various methods of urinary diversion. Recent contributions include the validation of HRQOL instruments specific to bladder c...

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

    Energy Technology Data Exchange (ETDEWEB)

    Coen, John J., E-mail: jcoen@harthosp.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Paly, Jonathan J.; Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Kaufman, Donald S. [Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Heney, Niall M. [Department of Urology, Massachusetts General Hospital, Boston, Massachusetts (United States); Spiegel, Daphne Y.; Efstathiou, Jason A.; Zietman, Anthony L.; Shipley, William U. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2013-06-01

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

  15. 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.

  16. GENETIC RISK MARKERS FOR SUPERFICIAL AND INVASIVE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    V. N. Pavlov

    2011-01-01

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

  17. Determining patient preferences for improved chemotoxicity during treatment for advanced bladder cancer

    DEFF Research Database (Denmark)

    Aristides, M.; Maase, Hans von der; Roberts, T.;

    2005-01-01

    Determining patient preferences for improved chemotoxicity during treatment for advanced bladder cancer Conventional treatment for advanced bladder cancer is methotrexate, vinblastine, doxorubicin plus cisplatin (MVAC), with a median survival of 1 year but significant toxicity. The newer...... combination of gemcitabine plus cisplatin (GC) has demonstrated comparable survival and an improved toxicity profile (Von der Maase et al. 2000). At present, the importance to patients of the toxicity of chemotherapy has not been widely studied. An earlier study in bladder cancer indicated that toxicity was...... an important determinant of treatment preference (Davey et al. 2000). A study of preferences for advanced bladder cancer therapy in the UK was proposed....

  18. Magnetic resonance diffusion-weighted whole-body imaging (DWIBS in bladder cancer diagnostics

    Directory of Open Access Journals (Sweden)

    Ponukalin A.N.

    2011-12-01

    Full Text Available The purpose of the article is to identify the most characteristic and significant changes in indicators in patients with bladder cancer during diffusion-weighted whole-body imaging (DWIBS. Materials: From September 2009 till 2011 98 patients have been examined (61 (62,24% with morphologically verified bladder cancer and 37 (37,76% with cystitis. Results: The study has revealed that the sensitivity of DWIBS-study in detecting bladder cancer is 98,36%, specificity of 10,81 %, the efficacy of 65,38%. Conclusions: DWIBS is an informative noninvasive method for screening diagnostics of bladder cancer, to identify suspicious areas on regional, and distant metastases

  19. [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.

  20. [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.

  1. 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.

  2. 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

  3. 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.

  4. 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...... were added to account for intra-fractional changes. Pre-treatment and weekly repeat magnetic resonance imaging (MRI) series were acquired in which a full three-dimensional (3D) volume was scanned every second min for 10 min (a total of 366 scans in 61 series). Initially, the bladder clinical target...... by the selected PTV. Population-based margins of 14 mm Sup/Ant, 9 mm Post and 5 mm Inf/Lat were sufficient to cover the bladder. Using patient-specific margins, the overlap between PTV and bowel-cavity was reduced from 137 cm(3) with the plan selection strategy to 24 cm(3). CONCLUSION: In this phase II ART trial...

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

    Science.gov (United States)

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

    2016-01-01

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

  6. 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.

  7. Intraoperative photodynamic therapy of bladder cancer with alasens (results of multicenter trial

    Directory of Open Access Journals (Sweden)

    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

  8. A clinical analysis and prognostic study of 187 cases with T1G3 bladder cancer%T1G3膀胱癌187例临床分析及预后研究

    Institute of Scientific and Technical Information of China (English)

    李晓东; 孙光; 刘晓强; 刘硕

    2011-01-01

    目的 分析T1G3膀胱癌的临床特点及复发、进展、死亡的风险因素,提高对T1G3膀胱癌的认识和治疗效果. 方法 收集1998年1月至2006年10月天津市泌尿外科研究所诊断为T1G3膀胱癌且资料完整的患者187例.男162例,女25例.年龄35~92岁,平均66岁.进行临床流行病学调查并随访预后情况.寿命表法估计1、2、3、5年复发率、进展率及死亡率.将年龄、性别、出现症状至就诊时间、有无肾积水、手术方式、术后是否即刻灌药、膀胱灌注药物种类、肿瘤直径、肿瘤数量、肿瘤形态、有无原位癌、复发次数、初次复发时间≤6个月作为变量,分别进行肿瘤复发、疾病进展、死亡的Kaplan-meier单因素及Cox多因素生存分析. 结果 本组患者随访12~111个月,平均46个月.肿瘤复发100例(53.5%),进展61例(32.6%),死亡37例(19.8%).1、2、3、5年肿瘤复发率分别为35.0%、60.0%、63.0%、65.0%,疾病进展率分别为12.0%、27.0%、34.0%、38.0%,死亡率分别为0、11.0%、17.0%、26.0%.肿瘤直径、肿瘤数量、即刻灌注、初次复发时间≤6个月是T1G3膀胱癌复发的危险因素;肿瘤形态、原位癌、初次复发时间≤6个月、复发次数是T1G3膀胱癌进展的危险因素.肿瘤进展是患者死亡的危险因素. 结论 肿瘤直径≥3 cm、多发、初次复发时间≤6个月的T1G3膀胱癌患者更容易复发,应加强随访,即刻膀胱灌注可以降低T1G3膀胱肿瘤复发的风险.对肿瘤形态呈结节状、合并原位癌、初次复发时间≤6个月、多次复发等进展高危风险因素的T1G3膀胱肿瘤患者,应早期行膀胱切除.%Objective The clinical features of T1G3 bladder cancer and the risk factors of the recurrence,progression and death were studied. Methods One hundred and eighty-seven cases with T1G3 bladder cancer were diagnosed from 1998 to 2006 in the Institute of Urology of Tianjin.There were 162

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

    Directory of Open Access Journals (Sweden)

    Montserrat García-Closas

    2007-02-01

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

  10. N-Acetyltransferase 1 (NAT1) Genotype: A Risk Factor for Urinary Bladder Cancer in a Lebanese Population

    Science.gov (United States)

    Yassine, Ibrahim A.; Kobeissi, Loulou; Jabbour, Michel E.; Dhaini, Hassan R.

    2012-01-01

    In Lebanon, bladder cancer is the second most incident cancer among men. This study investigates a possible association between N-acetyltransferase 1 (NAT1) genotype, a drug-metabolizing enzyme coding gene, and bladder cancer in Lebanese men. A case-control study (54 cases and 105 hospital-based controls) was conducted in two major hospitals in Beirut. Cases were randomly selected from patients diagnosed in the period of 2002–2008. Controls were conveniently identified and selected from the same settings. Data was collected using interview questionnaire and blood analysis. NAT1 genotypes were determined by PCR-RFLP. Statistical analysis revolved around univariate, bivariate, and multivariate logistic regression models, along with checks for effect modification. Results showed NAT1∗14A allele, smoking, occupational exposure to combustion fumes, and prostate-related symptoms, to be risk factors for bladder cancer. The odds of carrying at least one NAT1∗14A allele are 7 times higher in cases compared to controls (OR = 7.86, 95% CI: 1.53–40.39). A gene-environment interaction was identified for NAT1∗14A allele with occupational exposure to combustion fumes. Among carriers of NAT1∗14A allele, the odds of bladder cancer dropped to 2.03 from 3.72. Our study suggests NAT1∗14A allele as a possible biomarker for bladder cancer. Further research is recommended to confirm this association. PMID:22956951

  11. N-Acetyltransferase 1 (NAT1 Genotype: A Risk Factor for Urinary Bladder Cancer in a Lebanese Population

    Directory of Open Access Journals (Sweden)

    Ibrahim A. Yassine

    2012-01-01

    Full Text Available In Lebanon, bladder cancer is the second most incident cancer among men. This study investigates a possible association between N-acetyltransferase 1 (NAT1 genotype, a drug-metabolizing enzyme coding gene, and bladder cancer in Lebanese men. A case-control study (54 cases and 105 hospital-based controls was conducted in two major hospitals in Beirut. Cases were randomly selected from patients diagnosed in the period of 2002–2008. Controls were conveniently identified and selected from the same settings. Data was collected using interview questionnaire and blood analysis. NAT1 genotypes were determined by PCR-RFLP. Statistical analysis revolved around univariate, bivariate, and multivariate logistic regression models, along with checks for effect modification. Results showed NAT1∗14A allele, smoking, occupational exposure to combustion fumes, and prostate-related symptoms, to be risk factors for bladder cancer. The odds of carrying at least one NAT1∗14A allele are 7 times higher in cases compared to controls (OR=7.86, 95% CI: 1.53–40.39. A gene-environment interaction was identified for NAT1∗14A allele with occupational exposure to combustion fumes. Among carriers of NAT1∗14A allele, the odds of bladder cancer dropped to 2.03 from 3.72. Our study suggests NAT1∗14A allele as a possible biomarker for bladder cancer. Further research is recommended to confirm this association.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. White blood cell DNA adducts and fruit and vegetable consumption in bladder cancer.

    Science.gov (United States)

    Peluso, M; Airoldi, L; Magagnotti, C; Fiorini, L; Munnia, A; Hautefeuille, A; Malaveille, C; Vineis, P

    2000-02-01

    The 'Mediterranean diet', a diet rich in cereals, fruit and vegetables, has been associated with lowering the risk of a variety of cancers of the digestive tract and the bladder. In a previous study, we showed that the high phenolic content these dietary components produce in the urine could be associated with higher antimutagenic properties of the urine and lower arylamine-DNA adducts in exfoliated bladder cells. We have conducted a case-control study on 162 bladder cancer patients and 104 hospital controls. Total aromatic DNA adducts were measured in white blood cells (WBC) of all subjects by (32)P-post-labelling. Genetically based metabolic polymorphisms were analysed by PCR-RFLP (NAT2, GSTM1, GSTT1, GSTP1, COMT and NQO1). All subjects were interviewed about their tobacco use, dietary habits and other risk factors. The odds ratio (OR) for the risk of bladder cancer according to the presence/absence of WBC DNA adducts (detection limit 0.1 RALx10(8)) was 3.7 [95% confidence interval (CI) 2.2-6.3] and a dose-response relationship with levels of adducts was apparent. The association between case/control status and the presence of WBC DNA adducts was significantly stronger in the subjects who consumed fewer portions of fruit or vegetables per day (OR 7.80, 95% CI 3.0-20.30 for 0-1 portions of vegetables) than in the heavy consumers (OR 4.98 for consumers of 2 portions daily, OR 1.97 for consumers of > or =3 portions; similar but lower estimates were found for the intake of fruit). No association was noticed between tobacco smoking and WBC DNA adducts. Only NAT-2, among the several genotypes considered, was associated in a statistically significant way with the risk of bladder cancer (OR 1.72, 95% CI 1.03-2.87) and with the levels of WBC DNA adducts. Our report suggests that fruit and vegetables could protect against bladder cancer by inhibiting the formation of DNA adducts. PMID:10657956

  18. 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....... No correlation between plasma and urine TIMP-1 was found. Measurement of TIMP-1 in plasma and/or urine is apparently not useful for the identification of bladder cancer....

  19. 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.

  20. 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.

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

    Science.gov (United States)

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

    2010-01-01

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

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

    OpenAIRE

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

    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 use and bladder cancer risk remains inconclusive. Objective - In this study, we examined associations between personal use of permanent and temporary hair dyes and bladder cancer risk in a populati...

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

    OpenAIRE

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

    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 use and bladder cancer risk remains inconclusive. Objective In this study, we examined associations between personal use of permanent and temporary hair dyes and bladder cancer risk in a population-b...

  4. Interferon alfa in the treatment paradigm for non-muscle-invasive bladder cancer

    NARCIS (Netherlands)

    Lamm, D.; Brausi, M.; O'Donnell, M.A.; Witjes, J.A.

    2014-01-01

    OBJECTIVES: In this article, we review the various options for and the potential role of interferon alfa (IFN-alpha) in the treatment of non-muscle-invasive bladder cancer (NMIBC). METHODS: PubMed was searched for journal articles on IFN-alpha use in treating bladder cancer. The references listed in

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

    DEFF Research Database (Denmark)

    Munksgaard, P P; Mansilla, F; Brems Eskildsen, A-S;

    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...

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

    Directory of Open Access Journals (Sweden)

    Beebe-Dimmer Jennifer L

    2012-06-01

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

  7. 4-Aminobiphenyl-DNA adducts and p53 mutations in bladder cancer.

    Science.gov (United States)

    Martone, T; Airoldi, L; Magagnotti, C; Coda, R; Randone, D; Malaveille, C; Avanzi, G; Merletti, F; Hautefeuille, A; Vineis, P

    1998-02-01

    Epidemiologic studies have suggested that smokers of air-cured tobacco (rich in arylamines) are at higher risk of bladder cancer than smokers of flue-cured tobacco. The risk has been shown to be modulated by the N-acetyltransferase genotype. We analyzed the biopsies of 45 patients with bladder cancer. p53 mutations were sought by direct sequencing, and 4-aminobiphenyl-DNA adducts were measured by negative ion gas chromatography-mass spectrometry. 4-Aminobiphenyl-DNA adducts were higher in smokers of air-cured tobacco and in current smokers, but no relationship with the number of cigarettes smoked was found. Adducts were higher in more advanced histologic grades of tumors. No pattern was evident for p53 mutations. Seven of 9 mutations occurred in grade 3 tumors. No association was found between 4-ABP adducts and GSTM1 or NAT2 genetic polymorphisms. PMID:9466649

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-15

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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

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

    2016-04-01

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

  11. 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.

  12. The Immediate Results of Surgical Treatment of Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Alexei L. Charyshkin

    2016-06-01

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

  13. 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...

  14. Dairy intake and the risk of bladder cancer in the Netherlands Cohort Study on Diet and Cancer.

    Science.gov (United States)

    Keszei, András P; Schouten, Leo J; Goldbohm, R Alexandra; van den Brandt, Piet A

    2010-02-15

    The authors examined the association between the intake of different dairy products and the risk of bladder cancer in 120,852 men and women aged 55-69 years participating in the Netherlands Cohort Study on Diet and Cancer. Dairy product intake was assessed in 1986 by using a 150-item food frequency questionnaire. The cohort was followed for 16.3 years, and 1,549 incident cases of bladder cancer were analyzed. Cox proportional hazards analysis was applied with a case-cohort approach by using the follow-up data of a random subcohort (n = 5,000). Multivariate hazard ratio estimates comparing the highest with the lowest quintile of total dairy intake were 1.01 (95% confidence interval (CI): 0.81, 1.27; P(trend) = 0.68). A statistically significant association for fermented milk products was found only for the second quintile (median, 12 g/day) (hazard ratio = 0.71, 95% CI: 0.56, 0.91). Compared with nonconsumers, women with 25-75 g/day of butter consumption had a hazard ratio of 1.61 (95% CI: 1.03, 2.50; P(trend) cheese, calcium, lactose, or nonfermented dairy intake. These results provide weak evidence that bladder cancer risk is inversely associated with low intake of fermented dairy products and suggest a positive association with butter intake in women. PMID:20042437

  15. 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...... cancer risk therefore has been hypothesized to be stronger among slow acetylators. The few studies to formally explore such a possibility have produced inconsistent results, however. To assess this potential gene-environment interaction in as many bladder cancer studies as possible and to summarize...... results, we conducted a meta-analysis using data from 16 bladder cancer studies conducted in the general population (n = 1999 cases), Most had been conducted in European countries. Because control subjects were unavailable for a number of these studies, we used a case-series design, which can be used...

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

    Directory of Open Access Journals (Sweden)

    Oliveira Paula A

    2009-01-01

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

  17. Amygdalin Blocks Bladder Cancer Cell Growth In Vitro by Diminishing Cyclin A and cdk2

    OpenAIRE

    Jasmina Makarević; Jochen Rutz; Eva Juengel; Silke Kaulfuss; Michael Reiter; Igor Tsaur; Georg Bartsch; Axel Haferkamp; Blaheta, Roman A.

    2014-01-01

    Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml) on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP). Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regu...

  18. Effects of steroid sex hormones and adriamycin on human bladder cancer cells in culture.

    Directory of Open Access Journals (Sweden)

    Yoshimoto,Jun

    1982-02-01

    Full Text Available The effects of steroid sex hormones on the established cell lines derived from human urinary bladder cancer, T24, and from human transitional cell cancer of the urinary tract, 253J, were examined using the colony formation method. Of the seven kinds of steroid hormones tested, estradiol-17 beta was intensively cytotoxic for both cells. The cytotoxic effect was depended on the dose and time of treatment. The combined effect of Adriamycin and estradiol-17 beta on T24 cells could be recognized at low concentrations of Adriamycin (less than or equal to 10(-3 micrograms/ml after exposure for 24 h.

  19. Bladder preservation by internal iliac arterial infusion chemotherapy and irradiation in T3 bladder carcinoma patients over the age of 70 years

    Energy Technology Data Exchange (ETDEWEB)

    Hoshi, Senji; Shintaku, Ichiro; Suzuki, Ken-ichi; Takahashi, Toshiko; Kaihou, Yasuhiro; Ishidoya, Shigeto; Namima, Takashige; Ohyama, Chikara; Orikasa, Seiichi [Tohoku Univ., Sendai (Japan). School of Medicine

    2000-12-01

    Treatment by internal iliac arterial infusion chemotherapy (IA) combined with pelvic irradiation has proved to be effective for locally invasive bladder. Eight male patients, median age of 78 years (range 73-81) were enrolled. Pretreatment CT and whole layer core biopsy revealed T3a or T3b. Pelvic CT or fine needle aspiration biopsy following bipedal lymphography revealed N0 in 4 cases, N2 in 2 and N3 in 2, respectively. Three to 7 cycles of cisplatin (CDDP) 30-50 mg/m{sup 2}, methotrexate 20 mg/m{sup 2} and tetrahydropymnyl-adriamycin 20 mg/m{sup 2} every 3 week was administered combined with 40-50 Gy of whole pelvis irradiation. In 4 renal function impaired patients, 100 mg/m{sup 2} of carboplatin was administered instead of CDDP. All patients obtained complete response and the bladders were preserved. Observation periods were from 9 to 75 months (median 37 months). One N2 patient died with metastatic disease and two died without carcinoma. Two patients developed invasive bladder cancer on the side opposite to the primary tumors. Both were successfully treated by IA and irradiation. Bladders of all except one patient functioned for a long period. Side effects of IA and irradiation were not significant. IA combined with pelvic irradiation is effective and safe for elderly patients with bladder carcinoma. (author)

  20. Whole-genome sequencing identifies genomic heterogeneity at a nucleotide and chromosomal level in bladder cancer

    OpenAIRE

    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

    2014-01-01

    Genetic alterations are frequently observed in bladder cancer. In this study, we demonstrate that bladder tumors can be classified into two different types based on the spectrum of genetic diversity they confer. In one class of tumors, we observed tumor protein p53 mutations and a large number of single-nucleotide and structural variants. Another characteristic of this group was chromosome shattering, known as chromothripsis, and mutational heterogeneity. The other two bladder tumors did not ...

  1. Comparision of the second electric resection effects of two kinds of endoscopic resection in T1 G3 bladder cancer%T1G3期膀胱癌2种电切方式的二次电切疗效比较

    Institute of Scientific and Technical Information of China (English)

    张启发; 刘剑新; 韩孝州; 田长海; 张勇

    2015-01-01

    Objective:To evaluate the clinical effects of the second electric resection of two kinds of endoscopic resection in T1G3 bladder cancer. Methods:Eighty-two T1G3 bladder cancer patients diagnosed by pathological results of the first transurethral resection of bladder tumor(TURBT) were randomly divided into group A(38 cases) and group B(48 cases). Within postoperative 4 weeks,the group A and group B were treated with the second TURBT and transurethral plasma kinetic resection of bladder tumor,respectively. The time of operation and postoperative bladder irrigation, obturator nerve reflex rate, muscle layer lack rate and second postoperative pathological staging between two groups were compared. Results:The differences of the time of operation and postoperative bladder irrigation,obturator nerve reflex rate and muscle layer lack rate between two groups were statistically significant ( P 0. 05). Conclusions:The TURBT is less bleeding, clear cutting layer and good clinical effects, which can short the time of operation and postoperative bladder irrigation,reduce the obturator nerve reflex and improve the accuracy of tumor pathological stage.%目的::比较T1G3期膀胱癌2种电切方式的二次电切临床疗效。方法:将初次经尿道膀胱肿瘤电切术( TURBT)术后病理诊断为T1G3期膀胱癌患者82例,随机分为2组,术后4周内行第二次电切,其中38例行 TURBT,44例行经尿道等离子电切术。比较2组手术时间、术后膀胱冲洗时间、闭孔神经反射率、肌层缺失率及二次电切术后病理分期。结果:2组患者手术时间、术后膀胱冲洗时间、闭孔神经反射率和肌层缺失率差异均有统计学意义(P0.05)。结论:PKRBT出血少、切割层次清晰,可缩短手术时间及术后膀胱冲洗时间,降低术中闭孔神经反射,提高肿瘤病理分期准确性。

  2. 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.

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

    International Nuclear Information System (INIS)

    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. 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. 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. 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

  4. 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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Evanguelos Xylinas

    2016-09-01

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

  6. URODYNAMIC FINDINGS IN ASSESSMENT OF THE RESULTS OF PARTIAL CYSTECTOMY FOR BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    F. Sh. Engalychev

    2012-01-01

    Full Text Available Objectives. We determined the role of urodynamic results on the estimation of treatment efficiency of patients with bladder cancer.Subjects and methods. The study consequently included 160 patients receiving TUR and open resection in 2005−2009. Quality of life was assessed using the IPSS, QoL and International Inventory of Erectile Function (IIEF. Uroflowmetry, bladder diary were carried out to determine lower urinary tract symptoms befor treatment, 3 and 12 mo later.Results. In 3 months after operation statistically authentic changes of semiotics were noted. But in a year all indicators were in norm or approached to it.Conclusions. Urodinamic methods of research can be recommended to application as criterion of efficiency of operative intervention and for definition of rehabilitation times in the postoperative period in a complex with other methods.

  7. 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

    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 DC3...

  8. 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.

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

    Science.gov (United States)

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

    2015-08-01

    B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a common lymphoproliferative disorder with an increased risk of developing subsequent neoplasms of epithelial and mesenchymal origin. The decreased immunity and B-cell dysfunction in CLL probably accounts for this emergence of second malignancies. We report a case of synchronous bladder transitional cell carcinoma (TCC) and prostatic carcinoma with CLL. A 74-year-old male who underwent transurethral resection of the prostate (TURP) for benign prostatic hyperplasia 2 years before, presented with recurrent urinary tract infection. Peripheral blood smear revealed leukocytosis with absolute lymphocytosis (absolute lymphocyte count: 37870 cells/mm³). Flow cytometric immunophenotyping revealed 75% abnormal lymphoid cells which were positive for CD 19, CD5, CD23, CD22, CD200, CD20 (moderate) with lambda light chain restriction and negative for CD3, CD10, FMC7, CD38, CD138, IgM, CD103, CD123. F Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) showed increased metabolic activity of the left lateral wall of the urinary bladder extending to the left UV junction, adjacent part of trigone and bladder neck region along with multiple heterogeneous enhancing areas with increased FDG avidity within the prostate. Transurethral resection of the bladder tumour by cystoscopy was performed. Histopathology showed high grade, muscle invasive urothelial carcinoma. Due to presence of uptake in the prostate, transurethral resection of the prostate was done and histopathology revealed adenocarcinoma of prostate (prostate specific antigen- positive), Gleason grade III+III and Gleason score 6. A high index of suspicion is required to detect synchronous and metachronous malignancies. Ancillary studies such as immunohistochemistry, flow cytometry and PET/CT are often essential for detection and an accurate diagnosis. PMID:26277675

  10. Multimodal, 3D pathology-mimicking bladder phantom for evaluation of cystoscopic technologies (Conference Presentation)

    Science.gov (United States)

    Smith, Gennifer T.; Lurie, Kristen L.; Zlatev, Dimitar V.; Liao, Joseph C.; Ellerbee, Audrey K.

    2016-02-01

    Optical coherence tomography (OCT) and blue light cystoscopy (BLC) have shown significant potential as complementary technologies to traditional white light cystoscopy (WLC) for early bladder cancer detection. Three-dimensional (3D) organ-mimicking phantoms provide realistic imaging environments for testing new technology designs, the diagnostic potential of systems, and novel image processing algorithms prior to validation in real tissue. Importantly, the phantom should mimic features of healthy and diseased tissue as they appear under WLC, BLC, and OCT, which are sensitive to tissue color and structure, fluorescent contrast, and optical scattering of subsurface layers, respectively. We present a phantom posing the hollow shape of the bladder and fabricated using a combination of 3D-printing and spray-coating with Dragon Skin (DS) (Smooth-On Inc.), a highly elastic polymer to mimic the layered structure of the bladder. Optical scattering of DS was tuned by addition of titanium dioxide, resulting in scattering coefficients sufficient to cover the human bladder range (0.49 to 2.0 mm^-1). Mucosal vasculature and tissue coloration were mimicked with elastic cord and red dye, respectively. Urethral access was provided through a small hole excised from the base of the phantom. Inserted features of bladder pathology included altered tissue color (WLC), fluorescence emission (BLC), and variations in layered structure (OCT). The phantom surface and underlying material were assessed on the basis of elasticity, optical scattering, layer thicknesses, and qualitative image appearance. WLC, BLC, and OCT images of normal and cancerous features in the phantom qualitatively matched corresponding images from human bladders.

  11. 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

  12. Urinary bladder cancer risk factors in men: a Spanish case-control study.

    Science.gov (United States)

    Baena, Antonio Varo; Allam, Mohamed Farouk; Del Castillo, Amparo Serrano; Díaz-Molina, Carmen; Requena Tapia, Maria José; Abdel-Rahman, Amira Gamal; Navajas, Rafael Fernández-Crehuet

    2006-12-01

    The rising incidence of urinary bladder cancer is alarming and potential relationships with different risk factors have been postulated. The purpose of this study was to examine the possible relationship between different environmental risk factors and urinary bladder cancer. All men with urinary bladder cancer who were admitted to the Department of Urology of Reina Sofia University Hospital of Cordoba, Spain over 1 year were included in our study. Men were administered an interview questionnaire, which included data on history of known urinary bladder cancer risk factors. Comparisons between men with urinary bladder cancer (cases) and those with nonmalignant urological disease (controls) were made. The study included 74 cases and 89 controls. The variables associated with malignant lesions on univariate analysis were age, smoking and drinking alcohol. Meanwhile, fish, poultry and beef consumption were proved to be protective factors. The risk factors identified by the logistic regression analysis were age, smoking and fluid intake. The independent protective factors on the multivariate analysis were fish and poultry consumptions. Smoking was found to be the principal independent risk factors for urinary bladder cancer. Our results call for further investigation of urinary bladder cancer risk factors; future studies should preferably be performed on large prospective cohorts, to increase their validity. PMID:17106329

  13. 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

  14. Human urinary exosomes in bladder cancer patients : properties, concentrations and possible clinical application

    OpenAIRE

    Riches, Andrew Clive; Powis, Simon John; Mullen, Peter; Harrison, David James; Hacker, Christian; Lucocq, John Milton; Bowness, James Simeon; Chapman, Alex; Cameron, Ruth; McLornan, Liz; Chinn, David John; Leung, Steve

    2015-01-01

    OBJECTIVE: High grade bladder cancer is extremely aggressive. Early detection is thus an important challenge. De- velopment of non-invasive diagnostic tools particularly using urine samples could be of importance in the diagnosis and surveillance of these patients. Exosomes are small vesicles present in the urine and have the potential to be used as biomarkers of cancer. Thus studies of the properties and concentrations of these particles in bladder cancer patients are of importance.MATERIALS...

  15. 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...

  16. The progress in diagnostic imaging for staging of bladder and prostate cancer. Endorectal magnetic resonance imaging and magnetization transfer contrast

    Energy Technology Data Exchange (ETDEWEB)

    Arima, Kiminobu; Hayashi, Norio; Yanagawa, Makoto; Kawamura, Juichi; Kobayashi, Shigeki; Takeda, Kan [Mie Univ., Tsu (Japan). School of Medicine; Sugimura, Yoshiki

    1999-08-01

    We retrospectively studied the staging accuracy of endorectal magnetic resonance imaging (MRI) in comparison with transrectal ultrasound examination (TRUS) for 71 localized bladder cancers and 19 localized prostate cancers (PC) radically resected. The accuracy of clinical staging for bladder cancer in endorectal MRI and TRUS was 85.9% and 69.2%, respectively. The presence or absence of the continuity of submucosal enhancement on T2-weighted MRI images could be useful for the staging of bladder cancer. The accuracy of the seminal vesicular invasion for prostate cancer in endorectal MRI and TRUS was 95% and 63%, respectively. To determine whether magnetization transfer contrast (MTC) provides additional information in the diagnosis of prostate cancer, the magnetization transfer ratios (MTRs) were calculated in 22 patients with PC, 5 with benign prostatic hyperplasia (BPH) and 4 controls. The mean MTR in the peripheral zone of the normal prostate (8.0%{+-}3.4 [standard deviation]) showed a statistically significant decrease relative to that in the inner zone of the normal prostate (27.4%{+-}3.4, p<0.01), BPH (25.5%{+-}3.7, p<0.01), pre-treatment PC (30.6%{+-}5.9, p<0.01), and PC after hormonal therapy (20.3%{+-}6.3, p<0.01). The mean MTR in pre-treatment PC was significantly higher than that in BPH, or in PC after hormonal therapy (p<0.01). MTC was considered to be useful for conspicuity of prostate cancer lesion. (author)

  17. Results from a Phase I Study of Lapatinib with Gemcitabine and Cisplatin in Advanced or Metastatic Bladder Cancer

    DEFF Research Database (Denmark)

    Cerbone, Linda; Sternberg, Cora N; Sengeløv, Lisa;

    2016-01-01

    × 3 patients), 1 of the 6 patients presented DLTs (grade 4, treatment-related febrile neutropenia and renal failure). Twelve patients received 6 cycles. CONCLUSIONS: Lapatinib at 750-1,250 mg combined with GC appears safe and tolerable. The MTD of lapatinib combined with GC in bladder cancer was 1...

  18. Common genetic polymorphisms in pre-microRNAs and risk of bladder cancer

    OpenAIRE

    Deng, Shi; Wang, Wei; Xiang LI; Zhang, Peng

    2015-01-01

    Background At present, inconsistent association between single nucleotide polymorphism (SNP) in pre-miRNAs (hsa-mir-196a2 rs11614913 C/T, hsa-mir-499 rs3746444 A/G, and hsa-mir-146a rs2910164 C/G) and bladder cancer were obtained in limited studies. We performed a case–control study to test whether these three common polymorphisms are associated with bladder cancer. One hundred fifty-nine patients affected by bladder cancer and 298 unrelated healthy subjects were enrolled in the study. Method...

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

    OpenAIRE

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

    2013-01-01

    Urinary bladder cancer incidence in Lebanon ranks among the highest in the world. Cytochrome P450 2E1 (CYP2E1), NAD(P)H quinone oxidoreductase1 (NQO1), and N-Acetyltransferase1 (NAT1), are drug-metabolizing enzymes (DMEs) involved in the metabolism of carcinogens, such as arylamines and heterocyclic amines, implicated in bladder cancer. The present study attempts to investigate the role of these DMEs genetic polymorphism in bladder cancer risk among Lebanese men. 54 cases and 106 controls wer...

  20. Photo-thermal therapy of bladder cancer with Anti-EGFR antibody conjugated gold nanoparticles.

    Science.gov (United States)

    Chen, Chieh Hsiao; Wu, Yi-Jhen; Chen, Jia-Jin

    2016-01-01

    The aim of this study was to enhance the effectiveness of photo thermal therapy (PTT) in the targeting of superficial bladder cancers using a green light laser in conjunction with gold nanoparticles (GNPs) conjugated to antibody fragments (anti-EGFR). GNPs conjugated with anti-EGFR-antibody fragments were used as probes in the targeting of tumor cells and then exposed to a green laser (532nm), resulting in the production of sufficient thermal energy to kill urothelial carcinomas both in vitro and in vivo. Nanoparticles conjugated with antibody fragments are capable of damaging cancer cells even at relatively very low energy levels, while non-conjugated nanoparticles would require an energy level of 3 times under the same conditions. The lower energy required by the nanoparticles allows this method to destroy cancerous cells while preserving normal cells when applied in vivo. Nanoparticles conjugated with antibody fragments (anti-EGFR) require less than half the energy of non-conjugated nanoparticles to kill cancer cells. In an orthotopic bladder cancer model, the group treated using PTT presented significant differences in tumor development. PMID:27100501

  1. Simvastatin induces cell cycle arrest and inhibits proliferation of bladder cancer cells via PPARγ signalling pathway

    Science.gov (United States)

    Wang, Gang; Cao, Rui; Wang, Yongzhi; Qian, Guofeng; Dan, Han C.; Jiang, Wei; Ju, Lingao; Wu, Min; Xiao, Yu; Wang, Xinghuan

    2016-01-01

    Simvastatin is currently one of the most common drugs for old patients with hyperlipidemia, hypercholesterolemia and atherosclerotic diseases by reducing cholesterol level and anti-lipid properties. Importantly, simvastatin has also been reported to have anti-tumor effect, but the underlying mechanism is largely unknown. We collected several human bladder samples and performed microarray. Data analysis suggested bladder cancer (BCa) was significantly associated with fatty acid/lipid metabolism via PPAR signalling pathway. We observed simvastatin did not trigger BCa cell apoptosis, but reduced cell proliferation in a dose- and time-dependent manner, accompanied by PPARγ-activation. Moreover, flow cytometry analysis indicated that simvastatin induced cell cycle arrest at G0/G1 phase, suggested by downregulation of CDK4/6 and Cyclin D1. Furthermore, simvastatin suppressed BCa cell metastasis by inhibiting EMT and affecting AKT/GSK3β. More importantly, we found that the cell cycle arrest at G0/G1 phase and the alterations of CDK4/6 and Cyclin D1 triggered by simvastatin could be recovered by PPARγ-antagonist (GW9662), whereas the treatment of PPARα-antagonist (GW6471) shown no significant effects on the BCa cells. Taken together, our study for the first time revealed that simvastatin inhibited bladder cancer cell proliferation and induced cell cycle arrest at G1/G0 phase via PPARγ signalling pathway. PMID:27779188

  2. Pathological Characteristics of Primary Bladder Carcinoma Treated at a Tertiary Care Hospital and Changing Demographics of Bladder Cancer in Sri Lanka.

    Science.gov (United States)

    Sasikumar, S; Wijayarathna, K S N; Karunaratne, K A M S; Gobi, U; Pathmeswaran, A; Abeygunasekera, Anuruddha M

    2016-01-01

    Objectives. The aim was to compare demographics and pathological features of bladder carcinoma treated in a urology unit with findings of previous studies done in Sri Lanka. Materials and Methods. Data of newly diagnosed patients with bladder cancer in a tertiary referral centre from 2011 to 2014 were analysed. Data on bladder cancers diagnosed from 1993 to 2014 were obtained from previous publications and Sri Lanka Cancer Registry. Results. There were 148 patients and mean age was 65 years. Male to female ratio was 4.1 : 1. Urothelial carcinoma (UC) was found in 89.2% of patients. Muscle invasion was noted in 35% of patients compared to 48.4% two decades ago. In patients with UC, 16.5% were found to have pT1 high grade tumour. It was 5.3% from 1993 to 2000. Pure squamous cell carcinoma was found in 8.1% of patients while primary or de novo carcinoma in situ (not associated with high grade pT1 tumours) was seen in one patient only. Conclusions. The percentage of squamous carcinoma is higher among Sri Lankan patients while primary carcinoma in situ is a rarity. The percentage of muscle invasive disease has decreased while the percentage of pT1 high grade tumours has increased during the last two decades in Sri Lanka. PMID:26884756

  3. 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.

  4. 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.

  5. Inhibition of Autophagy Potentiates Atorvastatin-Induced Apoptotic Cell Death in Human Bladder Cancer Cells in Vitro

    Directory of Open Access Journals (Sweden)

    Minyong Kang

    2014-05-01

    Full Text Available Statins are cholesterol reduction agents that exhibit anti-cancer activity in several human cancers. Because autophagy is a crucial survival mechanism for cancer cells under stress conditions, cooperative inhibition of autophagy acts synergistically with other anti-cancer drugs. Thus, this study investigates whether combined treatment of atorvastatin and autophagy inhibitors results in enhancing the cytotoxic effects of atorvastatin, upon human bladder cancer cells, T24 and J82, in vitro. To measure cell viability, we performed the EZ-Cytox cell viability assay. We examined apoptosis by flow cytometry using annexin-V/propidium iodide (PI and western blot using procaspase-3 and poly (ADP-ribose polymerase (PARP antibodies. To examine autophagy activation, we evaluated the co-localization of LC3 and LysoTracker by immunocytochemistry, as well as the expression of LC3 and p62/sequestosome-1 (SQSTM1 by western blot. In addition, we assessed the survival and proliferation of T24 and J82 cells by a clonogenic assay. We found that atorvastatin reduced the cell viability of T24 and J82 cells via apoptotic cell death and induced autophagy activation, shown by the co-localization of LC3 and LysoTracker. Moreover, pharmacologic inhibition of autophagy significantly enhanced atorvastatin-induced apoptosis in T24 and J82 cells. In sum, inhibition of autophagy potentiates atorvastatin-induced apoptotic cell death in human bladder cancer cells in vitro, providing a potential therapeutic approach to treat bladder cancer.

  6. 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....... RESULTS: The cohort included 329,168 patients using ADD, and 307,315 controls with 1295 and 1071 patients, respectively, diagnosed as having UBC during follow-up. The adjusted HRs of UBC were 0.77 (95% CI 0.57 to 1.05) and 1.04 (95% CI 0.96 to 1.14) for type 1 and 2 diabetes, respectively. These results...

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

    Science.gov (United States)

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

    2013-01-01

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

  8. Muscle invasive bladder cancer in Upper Egypt: the shift in risk factors and tumor characteristics

    International Nuclear Information System (INIS)

    In Egypt, where bilharziasis is endemic, bladder cancer is the commonest cancer in males and the 2nd in females; squamous cell carcinoma (SCC) is the commonest type found, with a peculiar mode of presentation. The aim of this study is to identify and rank the risk factors of muscle invasive bladder cancer (MIBC) in Upper Egypt and describe its specific criteria of presentation and histopathology. This is an analytical, hospital based, case controlled study conducted in south Egypt cancer institute through comparing MIBC cases (n = 130) with age, sex and residence matched controls (n = 260) for the presence of risk factors of MIBC. Data was collected by personal interview using a well designed questionnaire. Patients' records were reviewed for histopathology and Radiologic findings. The risk factors of MIBC were positive family history [Adjusted odds ratio (AOR) = 7.7], exposure to pesticides [AOR = 6.2], bladder stones [AOR = 5], consanguinity [AOR = 3.9], recurrent cystitis [AOR = 3.1], bilharziasis [odds ratio (OR) = 5.8] and smoking [OR = 5.3]. SCC represented 67.6% of cases with burning micturition being the presenting symptom in 73.8%. MIBC in Upper Egypt is usually of the SCC type (although its percentage is decreasing), occurs at a younger age and presents with burning micturition rather than hematuria. Unlike the common belief, positive family history, parents' consanguinity, exposure to pesticides and chronic cystitis seem to play now more important roles than bilharziasis and smoking in the development of this disease in this area

  9. 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.

  10. Spotlight on differentially expressed genes in urinary bladder cancer.

    Directory of Open Access Journals (Sweden)

    Apostolos Zaravinos

    Full Text Available INTRODUCTION: We previously identified common differentially expressed (DE genes in bladder cancer (BC. In the present study we analyzed in depth, the expression of several groups of these DE genes. MATERIALS AND METHODS: Samples from 30 human BCs and their adjacent normal tissues were analyzed by whole genome cDNA microarrays, qRT-PCR and Western blotting. Our attention was focused on cell-cycle control and DNA damage repair genes, genes related to apoptosis, signal transduction, angiogenesis, as well as cellular proliferation, invasion and metastasis. Four publicly available GEO Datasets were further analyzed, and the expression data of the genes of interest (GOIs were compared to those of the present study. The relationship among the GOI was also investigated. GO and KEGG molecular pathway analysis was performed to identify possible enrichment of genes with specific biological themes. RESULTS: Unsupervised cluster analysis of DNA microarray data revealed a clear distinction in BC vs. control samples and low vs. high grade tumors. Genes with at least 2-fold differential expression in BC vs. controls, as well as in non-muscle invasive vs. muscle invasive tumors and in low vs. high grade tumors, were identified and ranked. Specific attention was paid to the changes in osteopontin (OPN, SPP1 expression, due to its multiple biological functions. Similarly, genes exhibiting equal or low expression in BC vs. the controls were scored. Significant pair-wise correlations in gene expression were scored. GO analysis revealed the multi-facet character of the GOIs, since they participate in a variety of mechanisms, including cell proliferation, cell death, metabolism, cell shape, and cytoskeletal re-organization. KEGG analysis revealed that the most significant pathway was that of Bladder Cancer (p = 1.5×10(-31. CONCLUSIONS: The present work adds to the current knowledge on molecular signature identification of BC. Such works should progress in order

  11. 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.

  12. 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.

  13. Lipiodol as a Fiducial Marker for Image-Guided Radiation Therapy for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Jessica M. Freilich

    2014-04-01

    Full Text Available Purpose To evaluate Lipiodol as a liquid, radio-opaque fiducial marker for image-guided radiation therapy (IGRT for bladder cancer.Materials and Methods Between 2011 and 2012, 5 clinical T2a-T3b N0 M0 stage II-III bladder cancer patients were treated with maximal transurethral resection of a bladder tumor (TURBT and image-guided radiation therapy (IGRT to 64.8 Gy in 36 fractions ± concurrent weekly cisplatin-based or gemcitabine chemotherapy. Ten to 15mL Lipiodol, using 0.5mL per injection, was injected into bladder submucosa circumferentially around the entire periphery of the tumor bed immediately following maximal TURBT. The authors looked at inter-observer variability regarding the size and location of the tumor bed (CTVboost on computed tomography scans with versus without Lipiodol.Results Median follow-up was 18 months. Lipiodol was visible on every orthogonal two-dimensional kV portal image throughout the entire, 7-week course of IGRT. There was a trend towards improved inter-observer agreement on the CTVboost with Lipiodol (p = 0.06. In 2 of 5 patients, the tumor bed based upon Lipiodol extended outside a planning target volume that would have been treated with a radiation boost based upon a cystoscopy report and an enhanced computed tomography (CT scan for staging. There was no toxicity attributable to Lipiodol.Conclusions Lipiodol constitutes a safe and effective fiducial marker that an urologist can use to demarcate a tumor bed immediately following maximal TURBT. Lipiodol decreases inter-observer variability in the definition of the extent and location of a tumor bed on a treatment planning CT scan for a radiation boost.

  14. 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.

  15. Lipiodol as a Fiducial Marker for Image-Guided Radiation Therapy for Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Freilich, Jessica M.; Spiess, Philippe E.; Biagioli, Matthew C.; Fernandez, Daniel C.; Shi, Ellen J.; Hunt, Dylan C.; Gupta, Shilpa; Wilder, Richard B., E-mail: richard.wilder@moffitt.org [Moffitt Cancer Center, Tampa, FL (United States)

    2014-03-15

    Purpose: To evaluate Lipiodol as a liquid, radio-opaque fiducial marker for image-guided radiation therapy (IGRT) for bladder cancer; Materials and Methods: Between 2011 and 2012, 5 clinical T2a-T3b N0 M0 stage II-III bladder cancer patients were treated with maximal transurethral resection of a bladder tumor (TURBT) and image-guided radiation therapy (IGRT) to 64.8 Gy in 36 fractions ± concurrent weekly cisplatin-based or gemcitabine chemotherapy. Ten to 15mL Lipiodol, using 0.5mL per injection, was injected into bladder submucosa circumferentially around the entire periphery of the tumor bed immediately following maximal TURBT. The authors looked at inter-observer variability regarding the size and location of the tumor bed (CTVboost) on computed tomography scans with versus without Lipiodol. Results: Median follow-up was 18 months. Lipiodol was visible on every orthogonal two-dimensional kV portal image throughout the entire, 7-week course of IGRT. There was a trend towards improved inter-observer agreement on the CTVboost with Lipiodol (p = 0.06). In 2 of 5 patients, the tumor bed based upon Lipiodol extended outside a planning target volume that would have been treated with a radiation boost based upon a cystoscopy report and an enhanced computed tomography (CT) scan for staging. There was no toxicity attributable to Lipiodol: Conclusions: Lipiodol constitutes a safe and effective fiducial marker that an urologist can use to demarcate a tumor bed immediately following maximal TURBT. Lipiodol decreases inter-observer variability in the definition of the extent and location of a tumor bed on a treatment planning CT scan for a radiation boost. (author)

  16. 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

  17. Mouse bladder wall injection.

    Science.gov (United States)

    Fu, Chi-Ling; Apelo, Charity A; Torres, Baldemar; Thai, Kim H; Hsieh, Michael H

    2011-07-12

    Mouse bladder wall injection is a useful technique to orthotopically study bladder phenomena, including stem cell, smooth muscle, and cancer biology. Before starting injections, the surgical area must be cleaned with soap and water and antiseptic solution. Surgical equipment must be sterilized before use and between each animal. Each mouse is placed under inhaled isoflurane anesthesia (2-5% for induction, 1-3% for maintenance) and its bladder exposed by making a midline abdominal incision with scissors. If the bladder is full, it is partially decompressed by gentle squeezing between two fingers. The cell suspension of interest is intramurally injected into the wall of the bladder dome using a 29 or 30 gauge needle and 1 cc or smaller syringe. The wound is then closed using wound clips and the mouse allowed to recover on a warming pad. Bladder wall injection is a delicate microsurgical technique that can be mastered with practice.

  18. 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.

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

    Science.gov (United States)

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

    2016-05-01

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

  20. Optimal management of asymptomatic workers at high risk of bladder cancer.

    Science.gov (United States)

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

    1986-01-01

    Many cohorts of industrial workers at increased risk of occupationally induced bladder cancer are still in the preclinical disease stage. A large proportion of workers in these populations have been exposed to aromatic amines, but have not yet experienced the average latent period for bladder cancer. A need exists for definition of what constitutes optimal management for asymptomatic workers in these cohorts. Promising advances in the epidemiology, pathology, detection, and treatment of bladder cancer pressure for a reassessment of current practices and the application of the most current scientific knowledge. Some of these apparent advances, however, have not yet been rigorously evaluated. The time has come to evaluate these advances so that their application can occur while high risk cohorts are still amenable to and likely to benefit from intervention. This commentary calls for such an evaluation leading to a comprehensive approach to managing cohorts at high risk of bladder cancer. PMID:3950777

  1. Human Papillomavirus Infection and Bladder Cancer Risk: A Meta-analysis

    OpenAIRE

    Li, Ni; Yang, Lin; Zhang, Yawei; Zhao, Ping; Zheng, Tongzhang; Dai, Min

    2011-01-01

    Background. Despite an increase in the number of molecular epidemiological studies conducted in recent years to evaluate the association between human papillomavirus (HPV) infection and risk of bladder cancer, the studies remain inconclusive.

  2. [Inhibitory effect of Chinese herb medicine zhuling on urinary bladder cancer. An experimental and clinical study].

    Science.gov (United States)

    Yang, D A

    1991-06-01

    Inhibitory effect of Zhuling (Grifola umbellata pilat) on urinary bladder cancer was determined experimentally and clinically. The results showed that zhuling inhibited significantly the induction of bladder cancer in rats exposed to N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), decreasing from 100% (18/18) in control group to 61.1% (11/18) in zhuling (P less than 0.01). Zhuling was given to 22 patients with recurrent bladder cancer after TUR or partial cystectomy. The patients were followed up for 12 to 38 months (average 26.5 months). Bladder cancer recurred in seven of the patients with a longer recurrence interval (19.2 months) after medication than before medication (P less than 0.05). The remaining 15 patients had no recurrence. The mechanism of Zhuling is discussed. PMID:1935440

  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. Magnetic resonance diffusion-weighted whole-body imaging (DWIBS in the urinary bladder cancer diagnostics

    Directory of Open Access Journals (Sweden)

    Viktor V. Zuev

    2012-09-01

    Full Text Available The purpose of the article is to identify the most characteristic and significant changes of magnetic resonance indicators in patients with the urinary bladder cancer during diffusion-weighed whole-body imaging (DWIBS. Materials: From September 2009 till April 2011 98 patients have been examined: 61 (62.2% with morphologically verified bladder cancer and 37 (37.8% with cystitis. Results: The study has revealed that the sensitivity of DWIBS investigation in detecting bladder cancer is 98.36%, specificity is 10.81, and the efficacy is 65.38%. Conclusions: DWIBS is an informative noninvasive method for screening diagnostics of bladder cancer, as well as for identificating suspicious areas of regional and distant metastases.

  5. 5-azacytidine inhibits the proliferation of bladder cancer cells via reversal of the aberrant hypermethylation of the hepaCAM gene.

    Science.gov (United States)

    Wang, Xiaorong; Chen, E; Yang, Xue; Wang, Yin; Quan, Zhen; Wu, Xiaohou; Luo, Chunli

    2016-03-01

    Hepatocyte cell adhesion molecule (hepaCAM), a tumor-suppressor gene, is rarely expressed in bladder carcinoma. However, little is known concerning the mechanisms of low hepaCAM expression in bladder cancer. Abnormal hypermethylation in the promoter plays a crucial role in cancer by silencing tumor-suppressor genes, which is catalyzed by DNA methyltransferases (DNMTs). In the present study, a total of 31 bladder cancer and 22 adjacent tissues were assessed by immunohistochemistry to detect DNMT3A/3B and hepaCAM expression. Methylation of hepaCAM was determined by methylation‑specific polymerase chain reaction (MSP). The mRNA and protein levels of DNMT3A/3B and hepaCAM were determined by RT-PCR and western blot analysis after treatment with 5-azacytidine (AZAC). Following AZAC treatment, the proliferation of bladder cancer cells was detected by CCK-8 and colony formation assays. Cell cycle distribution was examined by flow cytometry. To further evaluate the tumor‑suppressive roles of AZAC and the involved mechanisms, the anti-tumorigenicity of AZAC was tested in vivo. The expression of DNMT3A/3B protein was markedly increased in the bladder carcinoma tissues (P<0.05), and had a negative linear correlation with hepaCAM expression in the same patients according to Pearson's analysis (r=-0.7176/-0.7127, P<0.05). The MSP results indicated that the hepaCAM gene was hypermethylated in three bladder cancer cell lines. Furthermore, we found that downregulation of DNMT3A/3B expression, after treatment with AZAC, reversed the hypermethylation and expression of hepaCAM in bladder cancer cells. In addition, AZAC inhibited the proliferation of bladder cancer cells and arrested cells at the G0/G1 phase. The in vivo results showed that expression of DNMT3A/3B and hepaCAM as well as tumor growth of nude mice were markedly altered which corresponded with the in vitro results. Due to the ability to reactivate expression of hepaCAM and inhibit growth of bladder cancer cells

  6. Development and Characterization of Bladder Cancer Patient-Derived Xenografts for Molecularly Guided Targeted Therapy.

    Directory of Open Access Journals (Sweden)

    Chong-Xian Pan

    Full Text Available The overarching goal of this project is to establish a patient-derived bladder cancer xenograft (PDX platform, annotated with deep sequencing and patient clinical information, to accelerate the development of new treatment options for bladder cancer patients. Herein, we describe the creation, initial characterization and use of the platform for this purpose.Twenty-two PDXs with annotated clinical information were established from uncultured unselected clinical bladder cancer specimens in immunodeficient NSG mice. The morphological fidelity was maintained in PDXs. Whole exome sequencing revealed that PDXs and parental patient cancers shared 92-97% of genetic aberrations, including multiple druggable targets. For drug repurposing, an EGFR/HER2 dual inhibitor lapatinib was effective in PDX BL0440 (progression-free survival or PFS of 25.4 days versus 18.4 days in the control, p = 0.007, but not in PDX BL0269 (12 days versus 13 days in the control, p = 0.16 although both expressed HER2. To screen for the most effective MTT, we evaluated three drugs (lapatinib, ponatinib, and BEZ235 matched with aberrations in PDX BL0269; but only a PIK3CA inhibitor BEZ235 was effective (p<0.0001. To study the mechanisms of secondary resistance, a fibroblast growth factor receptor 3 inhibitor BGJ398 prolonged PFS of PDX BL0293 from 9.5 days of the control to 18.5 days (p<0.0001, and serial biopsies revealed that the MAPK/ERK and PIK3CA-AKT pathways were activated upon resistance. Inhibition of these pathways significantly prolonged PFS from 12 day of the control to 22 days (p = 0.001. To screen for effective chemotherapeutic drugs, four of the first six PDXs were sensitive to the cisplatin/gemcitabine combination, and chemoresistance to one drug could be overcome by the other drug.The PDX models described here show good correlation with the patient at the genomic level and known patient response to treatment. This supports further evaluation of the PDXs for their

  7. Regulation of UHRF1 by dual-strand tumor-suppressor microRNA-145 (miR-145-5p and miR-145-3p): inhibition of bladder cancer cell aggressiveness

    Science.gov (United States)

    Matsushita, Ryosuke; Yoshino, Hirofumi; Enokida, Hideki; Goto, Yusuke; Miyamoto, Kazutaka; Yonemori, Masaya; Inoguchi, Satoru; Nakagawa, Masayuki; Seki, Naohiko

    2016-01-01

    In microRNA (miRNA) biogenesis, the guide-strand of miRNA integrates into the RNA induced silencing complex (RISC), whereas the passenger-strand is inactivated through degradation. Analysis of our miRNA expression signature of bladder cancer (BC) by deep-sequencing revealed that microRNA (miR)-145-5p (guide-strand) and miR-145-3p (passenger-strand) were significantly downregulated in BC tissues. It is well known that miR-145-5p functions as a tumor suppressor in several types of cancer. However, the impact of miR-145-3p on cancer cells is still ambiguous. The aim of the present study was to investigate the functional significance of miR-145-3p and BC oncogenic pathways and targets regulated by miR-145-5p/miR-145-3p. Ectopic expression of either miR-145-5p or miR-145-3p in BC cells significantly suppressed cancer cell growth, migration and invasion and it also induced apoptosis. The gene encoding ubiquitin-like with PHD and ring finger domains 1 (UHRF1) was a direct target of these miRNAs. Silencing of UHRF1 induced apoptosis and inhibited cancer cell proliferation, migration, and invasion in BC cells. In addition, overexpressed UHRF1 was confirmed in BC clinical specimens, and the high UHRF1 expression group showed a significantly poorer cause specific survival rate in comparison with the low expression group. Taken together, our present data demonstrated that both strands of miR-145 (miR-145-5p: guide-strand and miR-145-3p: passenger-strand) play pivotal roles in BC cells by regulating UHRF1. The identification of the molecular target of a tumor suppressive miRNAs provides novel insights into the potential mechanisms of BC oncogenesis and suggests novel therapeutic strategies. PMID:27072587

  8. 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.

  9. The Health Economics of Bladder Cancer: A Comprehensive Review of the Published Literature

    OpenAIRE

    Botteman, Marc F; Pashos, Chris L; Alberto Redaelli; Benjamin Laskin; Robert Hauser

    2003-01-01

    The aim of this paper was to conduct a critical systematic review of the available literature on the clinical and economic burden of bladder cancer in developed countries, with a focus on the cost effectiveness of interventions aimed at reducing that burden. Forty-four economic studies were included in the review. Because of long- term survival and the need for lifelong routine monitoring and treatment, the cost per patient of bladder cancer from diagnosis to death is the highest of all cance...

  10. Local Immune Stimulation by Intravesical Instillation of Baculovirus to Enable Bladder Cancer Therapy

    OpenAIRE

    Wei Xia Ang; Ying Zhao; Timothy Kwang; Chunxiao Wu; Can Chen; Han Chong Toh; Ratha Mahendran; Kesavan Esuvaranathan; Shu Wang

    2016-01-01

    Intravesical instillation of Bacillus Calmette-Guérin is currently used as adjuvant therapy for superficial, non-muscle invasive bladder cancer (NMIBC). However, nearly 40% of patients with NMIBC will fail Bacillus Calmette-Guérin therapy. In an attempt to investigate the feasibility of using insect baculovirus-based vectors for bladder cancer therapy, we observed that intravesical instillation of baculoviruses without transgene up-regulated a set of Th1-type of cytokines and increased the su...

  11. Identification of gene expression patterns in superficial and invasive human bladder cancer

    DEFF Research Database (Denmark)

    Andersen, Thomas Thykjær; Workman, Christopher; Kruhøffer, Mogens;

    2001-01-01

    genes. The obtained expression data were sorted according to a weighting scheme and were subjected to hierarchical cluster analysis of tissues and genes. Northern blotting was used to verify the array data, and immunohistology was used to correlate between RNA and protein levels. Hierarchical clustering...... be identified in bladder cancer by combining oligonucleotide arrays and cluster analysis. These patterns give new biological insight and may form a basis for the construction of molecular classifiers and for developing new therapy for bladder cancer....

  12. Invasive Bladder Cancer after Cyclophosphamide Administration for Nephrotic Syndrome : A Case Report

    OpenAIRE

    Nakamoto, Takahisa; Kasaoka, Yoshinobu; Ikegami, Yoshihiko; Usui, Tsuguru

    2000-01-01

    We report a case of invasive bladder cancer after cyclophosphamide administration for nephrotic syndrome, and briefly discuss the association of bladder cancer and cyclophosphamide.  A 6-year-old boy, who was diagnosed as having nephrotic syndrome, was treated with oral administration of prednisolone and cyclophosphamide for 4 years, receiving a total dose of 49.5 g cyclophosphamide. At age 27, a gross hematuria with bloody clots appeared and he presented with postrenal renal failure. He unde...

  13. Clinical and pathological implications of miRNA in bladder cancer

    Directory of Open Access Journals (Sweden)

    Braicu C

    2015-01-01

    Full Text Available Cornelia Braicu,1 Roxana Cojocneanu-Petric,1,2 Sergiu Chira,1 Anamaria Truta,1,3 Alexandru Floares,4 Bogdan Petrut,5,6 Patriciu Achimas-Cadariu,7,8,* Ioana Berindan-Neagoe1,9–11,*1Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2Faculty of Biology and Geology, Babes-Bolyai University, Cluj-Napoca, Romania; 3Department of Medical Genetics, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 4Solutions of Artificial Intelligence Applications, Cluj-Napoca, Romania; 5Department of Urology, The Oncology Institute “ Prof Dr. Ion Chiricuta”, Cluj-Napoca, Romania; 6Department of Urology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 7Department of Surgery, The Oncology Institute “ Prof Dr. Ion Chiricuta”, Cluj-Napoca, Romania; 8Department of Surgical Oncology and Gynaecological Oncology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 9Department of Immunology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 10Department of Functional Genomics and Experimental Pathology, The Oncology Institute “ Prof Dr. Ion Chiricuta”, Cluj-Napoca, Romania; 11Department of Experimental Therapeutics M.D. Anderson Cancer Center Houston, TX, USAAbstract: MicroRNAs (miRNAs are small, noncoding RNA species with a length of 20–22 nucleotides that are recognized as essential regulators of relevant molecular mechanisms, including carcinogenesis. Current investigations show that miRNAs are detectable not only in different tissue types but also in a wide range of biological fluids, either free or trapped in circulating microvesicles. miRNAs were proven to be involved in cell communication, both in pathological and physiological processes. Evaluation of the global expression patterns of miRNAs provides key opportunities with

  14. Immunosensor for the ultrasensitive and quantitative detection of bladder cancer in point of care testing.

    Science.gov (United States)

    Chuang, Cheng-Hsin; Du, Yi-Chun; Wu, Ting-Feng; Chen, Cheng-Ho; Lee, Da-Huei; Chen, Shih-Min; Huang, Ting-Chi; Wu, Hsun-Pei; Shaikh, Muhammad Omar

    2016-10-15

    An ultrasensitive and real-time impedance based immunosensor has been fabricated for the quantitative detection of Galectin-1 (Gal-1) protein, a biomarker for the onset of multiple oncological conditions, especially bladder cancer. The chip consists of a gold annular interdigitated microelectrode array (3×3 format with a sensing area of 200µm) patterned using standard microfabrication processes, with the ability to electrically address each electrode individually. To improve sensitivity and immobilization efficiency, we have utilized nanoprobes (Gal-1 antibodies conjugated to alumina nanoparticles through silane modification) that are trapped on the microelectrode surface using programmable dielectrophoretic manipulations. The limit of detection of the immunosensor for Gal-1 protein is 0.0078mg/ml of T24 (Grade III) cell lysate in phosphate buffered saline, artificial urine and human urine samples. The normalized impedance variations show a linear dependence on the concentration of cell lysate present while specificity is demonstrated by comparing the immunosensor response for two different grades of bladder cancer cell lysates. We have also designed a portable impedance analyzing device to connect the immunosensor for regular checkup in point of care testing with the ability to transfer data over the internet using a personal computer. We believe that this diagnostic system would allow for improved public health monitoring and aid in early cancer diagnosis. PMID:26777732

  15. Modification of Alternative Splicing of Bcl-x Pre-mRNA in Bladder Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    ZHU Zhaohui; XING Shi'an; CHENG Ping; ZENG Fuqing; LU Gongcheng

    2006-01-01

    To modify the splicing pattern of Bcl-x and compare the effect of this approach with that of the antisense gene therapy in BIU-87 cell line of bladder cancer, by using 5'-Bcl-x AS to target downstream alternative 5'-Bcl-x splice site to shift splicing from Bcl-xL to Bcl-xS and 3'-Bcl-x AS antisense to the 3'-splice site of exon Ⅲ in Bcl-x pre- mRNA to down regulation of Bcl-xL expression,the inhibitory effects on cancer cells by modification of alternative splicing and antisense gene therapy were observed and compared by microscopy, MTT Assay, RT-PCR, FACS, Westhern bloting and clone formation. The growth of cells BIU-87 was inhibited in a dose- and time-dependent manner. Its inhibitory effect began 12 h after the exposure, reaching a maximum value after 72h. The number of cells decreased in S phase and the number increased in G1 phase. The ability to form foci was reduced and the antisense gene therapy was approximately half as efficient as modification of alternative splicing in inducing apoptosis. It is concluded that modification of splicing pattern of Bcl-x pre-mRNA in bladder cancer cell BIU-87 is better than antisense gene therapy in terms of tumor inhibition.

  16. 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.

  17. Systemic chemotherapy in inoperable or metastatic bladder cancer.

    Science.gov (United States)

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

    2006-04-01

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

  18. Role of chronic E. coli infection in the process of bladder cancer- an experimental study

    Directory of Open Access Journals (Sweden)

    El-Mosalamy Hala

    2012-08-01

    Full Text Available Abstract Background Bladder cancer is a common malignancy in Egypt. A history of urinary tract infection can be considered as a risk factor for bladder cancer. Escherichia coli (E. coli infection is responsible for 70% of urinary tract infection. This study aimed to evaluate the role of chronic E. coli infection during bladder carcinogenesis. In order to achieve this aim, we investigated the histopathological changes in bladder tissue and measured the level of nuclear factor kappa p65 (NF-κBp65, Bcl-2 and interleukin 6 (IL-6 in four groups each consisting of 25 male albino rats except of control group consisting of 20 rats. The first group was normal control group, the second group was infected with E. coli, the third group was administered nitrosamine precursor, and the forth group was infected with E. coli and administered nitrosamine precursor. Results The histopathological examination revealed that E. coli infected group was able alone to produce some histopathological changes in bladder tissue and that nitrosamine precursor plus E. coli group showed highest incidences of urinary bladder lesions than the nitrosamine precursor group. NF-κBp65, Bcl-2 and IL-6 levels were significantly higher in nitrosamine precursor plus E. coli group than the other groups. Conclusion These findings suggested that urinary bladder infection by E. coli may play a major additive and synergistic role during bladder carcinogenesis.

  19. 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.

  20. Genetic polymorphisms of MPO, COMT, MnSOD, NQO1, interactions with environmental exposures and bladder cancer risk.

    Science.gov (United States)

    Hung, Rayjean J; Boffetta, Paolo; Brennan, Paul; Malaveille, Christian; Gelatti, Umberto; Placidi, Donatella; Carta, Angela; Hautefeuille, Agnès; Porru, Stefano

    2004-06-01

    Tobacco smoking and occupational exposure are major risk factors of bladder cancer via exposure to polycyclic aromatic hydrocarbons (PAHs) and aromatic amines, which lead to oxidative stress and DNA damage. Several enzymes, which play key roles in oxidative stress are polymorphic in humans. Myeloperoxidase (MPO) produces a strong oxidant for microbicidal activity, and activates carcinogens in tobacco smoke. Catechol-O-methyltransferase (COMT) catalyzes the methylation of endo- and xenobiotics and prevents redox cycling. NAD(P)H:quinone oxidoreductase (NQO1) catalyzes the two-electron reduction of quinoid compounds, which also protects cells from redox cycling. Manganese superoxide dismutase (MnSOD) protects cells from free radical injury. To test the hypothesis that the risk of bladder cancer can be influenced by polymorphisms in the genes that modulate oxidative stress, in particular by interacting with environmental carcinogens, we conducted a hospital-based case-control study among men in Brescia, Northern Italy. We recruited and interviewed 201 incident cases and 214 controls from 1997 to 2000. Occupational exposures to PAHs and aromatic amines were coded blindly by occupational physicians. Unconditional multivariate logistic regression was applied to model the association between genetic polymorphisms and bladder cancer risk and the effect of modifications of smoking and occupational exposures were evaluated. MPO G-463A homozygous variant was associated with a reduced risk of bladder cancer with an OR of 0.31 (95% CI = 0.12-0.80). MnSOD Val/Val genotype increased the risk of bladder cancer with OR of 1.91 (95% CI = 1.20-3.04), and there was a combined effect with smoking (OR = 7.20, 95% CI = 3.23-16.1) and PAH (OR = 3.02, 95% CI = 1.35-6.74). We did not observe an effect of COMT Val108Met polymorphism. These findings suggest that individual susceptibility of bladder cancer may be modulated by MPO and MnSOD polymorphisms, and that the combination of genetic

  1. Significance of ERBB2 Overexpression in Therapeutic Resistance and Cancer-Specific Survival in Muscle-Invasive Bladder Cancer Patients Treated With Chemoradiation-Based Selective Bladder-Sparing Approach

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Masaharu [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Koga, Fumitaka, E-mail: f-koga@cick.jp [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Yoshida, Soichiro [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Tamura, Tomoki [Department of Pathology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Fujii, Yasuhisa [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Ito, Eisaku [Department of Pathology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Kihara, Kazunori [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan)

    2014-10-01

    Purpose: To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. Methods and Materials: From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. Results: CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). Conclusions: ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder

  2. Credentialing of radiotherapy centres for a clinical trial of adaptive radiotherapy for bladder cancer (TROG 10.01)

    International Nuclear Information System (INIS)

    Background: Daily variations in bladder filling make conformal treatment of bladder cancer challenging. On-line adaptive radiotherapy with a choice of plans has been demonstrated to reduce small bowel irradiation in single institution trials. In order to support a multicentre feasibility clinical trial on adaptive radiotherapy for bladder cancer (TROG 10.01) a credentialing programme was developed for centres wishing to participate. Methods: The credentialing programme entails three components: a facility questionnaire; a planning exercise which tests the ability of centres to create three adaptive plans based on a planning and five cone beam CTs; and a site visit during which image quality, imaging dose and image guidance procedures are assessed. Image quality and decision making were tested using customised inserts for a Perspex phantom (Modus QUASAR) that mimic different bladder sizes. Dose was assessed in the same phantom using thermoluminescence dosimetry (TLD). Results: All 12 centres participating in the full credentialing programme were able to generate appropriate target volumes in the planning exercise and identify the correct target volume and position the bladder phantom in the phantom within 3 mm accuracy. None of the imaging doses exceeded the limit of 5 cGy with a CT on rails system having the lowest overall dose. Conclusion: A phantom mimicking the decision making process for adaptive radiotherapy was found to be well suited during site visits for credentialing of centres participating in a clinical trial of adaptive radiotherapy for bladder cancer. Combined with a planning exercise the site visit allowed testing the ability of centres to create adaptive treatment plans and make appropriate decisions based on the volumetric images acquired at treatment.

  3. Time course of late rectal- and urinary bladder side effects after MRI-guided adaptive brachytherapy for cervical cancer

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    Georg, P.; Georg, D.; Poetter, R.; Doerr, W. [Medical University Vienna/ AKH Wien (Austria). Dept. of Radiooncology; Medical University Vienna (Austria). Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology; Medical University Vienna/ AKH Wien (Austria). Comprehensive Cancer Centre; Boni, A.; Ghabuous, A. [Medical University Vienna/ AKH Wien (Austria). Dept. of Radiooncology; Goldner, G.; Schmid, M.P. [Medical University Vienna/ AKH Wien (Austria). Dept. of Radiooncology; Medical University Vienna/ AKH Wien (Austria). Comprehensive Cancer Centre

    2013-07-15

    Background and purpose: To analyze the time course of late rectal- and urinary bladder complications after brachytherapy for cervical cancer and to compare the incidence- and prevalence rates thereof. Patients and methods: A total of 225 patients were treated with external-beam radiotherapy (EBRT) and magnetic resonance imaging (MRI)-guided brachytherapy with or without chemotherapy. Late side effects were assessed prospectively using the Late Effects in Normal Tissue - Subjective, Objective, Management and Analytic (LENT/SOMA) scale. The parameters analyzed were time to onset, duration, actuarial incidence- (occurrence of new side effects during a defined time period) and prevalence rates (side effects existing at a defined time point). Results: Median follow-up was 44 months. Side effects (grade 1-4) in rectum and bladder were present in 31 and 49 patients, 14 and 27 months (mean time to onset) after treatment, respectively. All rectal and 76 % of bladder side effects occurred within 3 years after radiotherapy. Mean duration of rectal events was 19 months; 81 % resolved within 3 years of their initial diagnosis. Mean duration of bladder side effects was 20 months; 61 % resolved within 3 years. The 3- and 5-year actuarial complication rates were 16 and 19 % in rectum and 18 and 28 % in bladder, respectively. The corresponding prevalence rates were 9 and 2 % (rectum) and 18 and 21 % (bladder), respectively. Conclusion: Late side effects after cervical cancer radiotherapy are partially reversible, but their time course is organ-dependent. The combined presentation of incidence- and prevalence rates provides the most comprehensive information. (orig.)

  4. 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.

  5. Variants of MUC5B minisatellites and the susceptibility of bladder cancer.

    Science.gov (United States)

    Ahn, Eun-Kyung; Kim, Wun-Jae; Kwon, Jeong-Ah; Choi, Phil-Jo; Kim, Woo Jin; Sunwoo, Yangil; Heo, Jeonghoon; Leem, Sun-Hee

    2009-04-01

    The human MUC5B gene, which is primarily expressed in the tracheobronchial tract, is clustered to chromosome 11p15.5 with three other secreted gel-forming mucins, MUC6, MUC2, and MUC5AC. In this study, we identified seven variable number of tandem repeats (VNTRs; minisatellites) from the entire MUC5B region. Six (MUC5B-MS1, -MS2, -MS3, -MS4, -MS5, and -MS7) of the seven minisatellites evaluated in this study were novel minisatellites, but the MUC5B-MS6 minisatellite was described in a previous study. These minisatellites of MUC5B were analyzed in genomic DNA extracted from controls, cancer patients, and multigenerational families. Three (MUC5B-MS3, -MS6, and -MS7) of the seven minisatellites were found to be polymorphic and transmitted through meiosis following Mendelian inheritance in seven families; therefore, these minisatellite polymorphisms could be useful as markers for paternity mapping and DNA fingerprinting. In addition, we evaluated allelic variation in these minisatellites to determine if such variation affected the susceptibility to various carcinomas. To accomplish this, we conducted a case-control study in which the genomic DNA of 789 cancer-free controls and cancer patients with five types of cancer were compared. A statistically significant association between the long rare MUC5B-MS6 alleles and the occurrence of bladder cancer was identified in the younger group (<60; odds ratio, 4.54; 95% confidence interval, 1.0-20.7; p=0.03). This observation suggests that the long rare MUC5B-MS6 alleles evaluated in this study could be used to identify the risk of bladder cancer. PMID:19191526

  6. Different glycosylation of cadherins from human bladder non-malignant and cancer cell lines

    Directory of Open Access Journals (Sweden)

    Lityńska Anna

    2002-06-01

    Full Text Available Abstract Background The aim of the present study was to determine whether stage of invasiveness of bladder cancer cell lines contributes to alterations in glycan pattern of their cadherins. Results Human non-malignant epithelial cell of ureter HCV29, v-raf transfected HCV29 line (BC3726 and transitional cell cancers of urine bladder Hu456 and T24 were grown in cell culture. Equal amounts of protein from each cell extracts were separated by SDS-PAGE electrophoresis and were blotted on an Immobilon P membrane. Cadherins were immunodetected using anti-pan cadherin mAb and lectin blotting assays were performed, in parallel. N-oligosaccharides were analysed by specific reaction with Galanthus nivalis agglutinin (GNA, Sambucus nigra agglutinin (SNA, Maackia amurensis agglutinin (MAA, Datura stramonium agglutinin (DSA, Aleuria aurantia agglutinin (AAA, Phaseolus vulgaris agglutinin (PHA-L and wheat germ agglutinin (WGA. The cadherin from HCV29 cell line possessed bi- and/or 2,4-branched triantennary complex type glycans, some of which were α2,6-sialylated. The cadherin from BC3726 cell line exhibited exclusively high mannose type glycans. Cadherins from Hu456 and T24 cell lines expressed high mannose type glycans as well as β1,6-branched oligosaccharides with poly-N-acetyllactosamine structures and α2,3-linked sialic acid residues. Additionally, the presence of fucose and α2,6-sialic acid residues on the cadherin from T24 cell line was detected. Conclusions These results indicate that N-glycosylation pattern of cadherin from bladder cancer cell line undergoes modification during carcinogenesis.

  7. Amygdalin Blocks Bladder Cancer Cell Growth In Vitro by Diminishing Cyclin A and cdk2

    Science.gov (United States)

    Makarević, Jasmina; Rutz, Jochen; Juengel, Eva; Kaulfuss, Silke; Reiter, Michael; Tsaur, Igor; Bartsch, Georg; Haferkamp, Axel; Blaheta, Roman A.

    2014-01-01

    Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25–10 mg/ml) on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP). Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR) related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug. PMID:25136960

  8. Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyclin A and cdk2.

    Directory of Open Access Journals (Sweden)

    Jasmina Makarević

    Full Text Available Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP. Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug.

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

    Science.gov (United States)

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

    2003-12-15

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

  10. 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.

  11. A new technique of bladder neck reconstruction during radical prostatectomy in patients with prostate cancer

    Directory of Open Access Journals (Sweden)

    Yuri Tolkach

    2015-06-01

    Full Text Available ABSTRACTPurpose:To evaluate continence after radical prostatectomy in prostate cancer patients, in whom a new method of the bladder neck reconstruction (BNR using deep dorsal stitch was implemented (deep single stitch through all bladder layers directly dorsal to the bladder opening after “tennis racket” reconstruction and to provide justification for its use by means of anatomical study in cadavers.Material and Methods:Open radical retropubic prostatectomy was performed in 84 patients: 39 patients with a new BNR method used to improve continence and control group of 45 patients with standard “tennis racket” BNR. Median follow-up was 14 months in control group and 12 months in study group. Continence recovery was accessed early postoperatively and every 3 months thereafter. Anatomical study was performed on 2 male fresh cadavers reproducing two different BNR techniques to clarify any underlying continence related mechanisms.Results:Patients with new BNR achieved full continence significantly faster (p=0.041, but the continence rates after 12 months were similar between groups. The severity of incontinence up to month 9 was significantly reduced in BNR group. The anastomotic stricture rate was not affected. Applying new BNR to the cadaver model revealed effects on early continence, namely presence of proximal passive closure mechanism in area of bladder neck.Conclusions:Continence in patients with the new BNR method using deep dorsal stitch recovered significantly faster. Moreover, a reduced grade of residual incontinence was documented. The effect was non-significant at month 12 of follow-up, meaning that only early effect was present.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-01

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

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

    International Nuclear Information System (INIS)

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

  14. Growth inhibiting effects of antisense eukaryotic expression vector of proliferating cell nuclear antigen gene on human bladder cancer cells

    Institute of Scientific and Technical Information of China (English)

    童强松; 曾甫清; 林晨; 赵军; 鲁功成

    2003-01-01

    Objective To explore the growth inhibiting effects on human bladder cancer by antisense RNA targeting the proliferating cell nuclear antigen (PCNA) gene. Methods The eukaryotic expression vector for antisense PCNA cDNA was constructed and transferred into a bladder cancer EJ cell line. The PCNA expression in the cancer cells was detected by RT-PCR and Western blotting assays. The in vitro proliferation activities of the transferred cells were observed by growth curve, tetrazolium bromide (MTT) colorimetry, tritiated thymidine (3H-TdR)incorporation, flow cytometry and clone formation testing, while its in vivo anti-tumor effects were detected on nude mice allograft models.Results After the antisense vector, pLAPSN, was transferred, cellular PCNA expression was inhibited at both protein and mRNA levels. The growth rates of EJ cells were reduced from 27.91% to 62.07% (P<0.01), with an inhibition of DNA synthesis rate by 52.31% (P<0.01). Transferred cells were blocked at G0/G1 phases in cell-cycle assay, with the clone formation ability decreased by 50.81% (P<0.01). The in vivo carcinogenic abilities of the transferred cancer cells were decreased by 54.23% (P<0.05). Conclusions Antisense PCNA gene transfer could inhibit the growth of bladder cancer cells in vitro and in vivo, which provided an ideal strategy for gene therapy of human cancers.

  15. Effect of small interfering RNA targeting survivin gene on biological behaviour of bladder cancer

    Institute of Scientific and Technical Information of China (English)

    HOU Jian-quan; HE Jun; WANG Xiao-lin; WEN Duan-gai; CHEN Zi-xing

    2006-01-01

    Background Bladder cancer is the most common type of urinary system tumours. It is frequently associated with genetic mutations that deregulate the cell cycle and render these tumours resistant to apoptosis. Survivin, a newly discovered member inhibitor of apoptosis protein (IAP) family in several human cancers, by inducing cell proliferation and inhibiting apoptosis is frequently activated in bladder cancer. We studied the influence of small interfering RNA (siRNA) targeting survivin on the biological behaviour of bladder cancer cells.Methods A double strand survivin target sequence specific siRNA was designed and synthesized. After transfection of bladder cancer cell line T24 by siRNA/liposome complex with increasing concentrations(50-200 nmol/L), the transfectant cells were intratumourally injected at different doses (5 μg or 50μg). The effects were measured in vitro and in vivo.Results The selected siRNA efficiently down-regulated survivin mRNA expression in a dose and time dependent manner. The maximal effect was achieved at the concentration of 100 nmol/L, at which survivin expression level was down-regulated by 75.91%. The inhibition rate of cell growth was 55.29% (P<0.01) and the markedly increased apoptotic rate was 45.70% (P<0.01). In vivo intratumoural injection of 50 μg siRNA-survivin could notably prevent the growth of bladder cancer (P<0.01) in xenografted animals.Conclusion The application of siRNA-survivin could markedly inhibit survivin expression in bladder cancer cell line by inducing apoptosis and inhibiting the growth of the tumour. It may become a new gene therapy tool for bladder cancer.

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

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

    International Nuclear Information System (INIS)

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

  18. Apoptosis inducing effects of arsenic trioxide on human bladder cancer cell line BIU-87

    Institute of Scientific and Technical Information of China (English)

    童强松; 曾甫清; 赵军; 鲁功成; 郑丽端

    2001-01-01

    Objective To explore the apoptosis inducing effects of arsenictrioxide (As2O3) on human bladder cancer cells and elucidate possible mechanisms. Methods After treatment with As2O3, the growth inhibition rates of human bladder cancer cell line BIU-87 were studied by MTT and cell counts methods. DNA synthesis rates were detected by 3 H-TdR assay. The morphological changes of cancer cells were observed by light and electronic microscopy and cell apoptosis rates were detected by TdT-mediated dUTP nick end labeling (TUNEL). bcl-2 gene expression of BIU-87 cells was observed by strept avidin-biotin complex (SABC) immunohistochemical method. Results As2O3 could effectively inhibit the growth of BIU-87 (P<0.05), which were time and concentration dependent. The inhibition rate of 4.0?μmol/L As2O3 for DNA synthesis of cancer cells was 55.64% (P<0.01). Partial cancer cells presented the characteristic morphological changes of apoptosis which depended on the time of exposure to drug (P<0.05). bcl-2 expression of BIU-87 cells was decreased significantly (P<0.05). Conclusion As2O3 can significantly induce apoptosis in bladder cancer cells by down-regulating the expression of the bcl-2 gene and inhibiting DNA synthesis. This provides a potentially effective method for prevention and cure of human bladder cancer.%目的观察三氧化二砷(As2O3)对人膀胱癌细胞的诱导凋亡作用并探讨其机制。方法采用细胞计数和MTT法检测As2O3对人膀胱癌细胞株BIU-87的生长抑制作用;采用3H-TdR掺入法 检测癌细胞DNA合成速率;采用普通光镜、透射电镜观察癌细胞形态学变化;采用TUNEL检测癌细胞凋 亡比率;采用SABC免疫组化观察BIU-87细胞中bcl-2的表达变化。 结果As2O3可有效地抑制BIU-87细胞的体外生长(P<0.05),并具有时间及浓度依赖性的特点。经 4μmol/LAs2O3作用后,癌细胞DNA合成抑制率为55.64%。部分膀胱癌细胞体积缩小、核固缩、染色质核 膜下聚

  19. Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells

    Science.gov (United States)

    Matsumoto, Ryuji; Tsuda, Masumi; Yoshida, Kazuhiko; Tanino, Mishie; Kimura, Taichi; Nishihara, Hiroshi; Abe, Takashige; Shinohara, Nobuo; Nonomura, Katsuya; Tanaka, Shinya

    2016-01-01

    In treating bladder cancer, determining the molecular mechanisms of tumor invasion, metastasis, and drug resistance are urgent to improving long-term patient survival. One of the metabolic enzymes, aldo-keto reductase 1C1 (AKR1C1), plays an essential role in cancer invasion/metastasis and chemoresistance. In orthotopic xenograft models of a human bladder cancer cell line, UM-UC-3, metastatic sublines were established from tumors in the liver, lung, and bone. These cells possessed elevated levels of EMT-associated markers, such as Snail, Slug, or CD44, and exhibited enhanced invasion. By microarray analysis, AKR1C1 was found to be up-regulated in metastatic lesions, which was verified in metastatic human bladder cancer specimens. Decreased invasion caused by AKR1C1 knockdown suggests a novel role of AKR1C1 in cancer invasion, which is probably due to the regulation of Rac1, Src, or Akt. An inflammatory cytokine, interleukin-1β, was found to increase AKR1C1 in bladder cancer cell lines. One particular non-steroidal anti-inflammatory drug, flufenamic acid, antagonized AKR1C1 and decreased the cisplatin-resistance and invasion potential of metastatic sublines. These data uncover the crucial role of AKR1C1 in regulating both metastasis and drug resistance; as a result, AKR1C1 should be a potent molecular target in invasive bladder cancer treatment. PMID:27698389

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

    Directory of Open Access Journals (Sweden)

    Xie LG

    2015-12-01

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

  1. Combined RASSF1A and RASSF2A Promoter Methylation Analysis as Diagnostic Biomarker for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Wei Meng

    2012-01-01

    Full Text Available Promoter hypermethylation, a widely studied epigenetic event known to influence gene expression levels, has been proposed as a potential biomarker in multiple types of cancer. Clinical diagnostic biomarkers are needed for reliable prediction of bladder cancer recurrence. In this paper, DNA promoter methylation of five C-terminal Ras-association family members (RASSF1A, RASSF2A, RASSF4, RASSF5, and RASSF6 was studied in 64 formalin-fixed paraffin-embedded (FFPE bladder cancer and normal adjacent tissues using methylation-specific high-resolution melting (MS-HRM analysis. Results showed that 73% (30/41 of transitional cell carcinoma, 100% (3/3 of squamous cell carcinoma, and 100% (4/4 of small cell carcinoma demonstrated promoter methylation of the RASSF1A or RASSF2A gene, but only 6% (1/16 of normal tissues had promoter methylation of RASSF genes. Testing positive for hypermethylation of RASSF1A or RASSF2A promoter provided 77% sensitivity and 94% specificity for identification of cancer tissues with an area under the curve of 0.854, suggesting that promoter methylation analysis of RASSF1A and RASSF2A genes has potential for use as a recurrence biomarker for bladder cancer patients.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. Next generation of optical diagnostics for bladder cancer using probe-based confocal laser endomicroscopy

    Science.gov (United States)

    Liu, Jen-Jane; Chang, Timothy C.; Pan, Ying; Hsiao, Shelly T.; Mach, Kathleen E.; Jensen, Kristin C.; Liao, Joseph C.

    2012-02-01

    Real-time imaging with confocal laser endomicroscopy (CLE) probes that fit in standard endoscopes has emerged as a clinically feasible technology for optical biopsy of bladder cancer. Confocal images of normal, inflammatory, and neoplastic urothelium obtained with intravesical fluorescein can be differentiated by morphologic characteristics. We compiled a confocal atlas of the urinary tract using these diagnostic criteria to be used in a prospective diagnostic accuracy study. Patients scheduled to undergo transurethral resection of bladder tumor underwent white light cystoscopy (WLC), followed by CLE, and histologic confirmation of resected tissue. Areas that appeared normal by WLC were imaged and biopsied as controls. We imaged and prospectively analyzed 135 areas in 57 patients. We show that CLE improves the diagnostic accuracy of WLC for diagnosing benign tissue, low and high grade cancer. Interobserver studies showed a moderate level of agreement by urologists and nonclinical researchers. Despite morphologic differences between inflammation and cancer, real-time differentiation can still be challenging. Identification of bladder cancer-specific contrast agents could provide molecular specificity to CLE. By using fluorescently-labeled antibodies or peptides that bind to proteins expressed in bladder cancer, we have identified putative molecular contrast agents for targeted imaging with CLE. We describe one candidate agent - anti-CD47 - that was instilled into bladder specimens. The tumor and normal urothelium were imaged with CLE, with increased fluorescent signal demonstrated in areas of tumor compared to normal areas. Thus, cancer-specificity can be achieved using molecular contrast agents ex vivo in conjunction with CLE.

  8. 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.

  9. Long-term urodynamic evaluation of laparoscopic radical cystectomy with orthotopic ileal neobladder for bladder cancer.

    Science.gov (United States)

    Wang, Dong; Li, Li-Jun; Liu, Jing; Qiu, Ming-Xing

    2014-09-01

    The long-term urodynamics of laparoscopic radical cystectomy with orthotopic ileal neobladder for bladder cancer remain unclear in the clinical setting. The present prospective observational study was conducted between January 2010 and December 2012 to evaluate the 6-month and 12-month follow-up data of urodynamic changes of bladder cancer patients who were initially treated by laparoscopic radical cystectomy with orthotopic ileal neobladder. A total of 53 eligible patients were included, and all patients were followed up for at least 12 months, with a median time of 18 months. During the follow-up period, no patients reported difficulty urinating, and the daily frequency of urination and the urine output were gradually improved with time. Dynamic urodynamic examinations showed that the maximum flow rate (11.4±1.1 vs. 7.3±1.4 ml/sec; Pcompliance (26.9±13 vs. 27.4±13.1 cm H2O; P=0.848) at 12 and 6 months after initial surgical treatment. In conclusion, the urodynamics of this orthotopic ileal neobladder gradually improve, and its long-term urine storage and voiding functions are acceptable. PMID:25120652

  10. 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.

  11. 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%).

  12. 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.

  13. 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

  14. 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

  15. 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

  16. Telomerase Activity, Cytokeratin 20 and Cytokeratin 19 in Urine Cells of Bladder Cancer Patients

    International Nuclear Information System (INIS)

    Aim of the Study: This work aims to search for markers suitable for the screening of bladder cancer, which should be specific, sensitive, reproducible, non-invasive and at acceptable cost. Patients and Methods: The study included 50 patients diagnosed as bladder cancer (35 TCC, 15 SCC) of different stages and grades, 30 patients with various urothelial diseases, besides 20 apparently healthy subjects of matched age and sex to the malignant group. A random midstream urine sample was collected in a sterile container for the determination of telomerase by RT-PCR, keratin 19 by ELSA CYFRA 21-1 IRMA kit, keratin 20 by RT-PCR and immunohistochemical staining, and urine cytology. Results: For all parameters (telomerase, K19, K20 and cytology) the malignant group was significantly different from both the benign and the control groups. None of the four studied parameters was correlated to the stage of the disease, and when it comes to grade, only KI9 showed a significant positive correlation with grade both in TCC and SCe. When ROC curves for all parameters were compared, K 19 had the largest area under the curve, and then comes K20 . o Conclusion: K 19 may be used as a biological marker for the diagnosis of bladder cancer. K 19 could not be used for differential diagnosis of different types of bladder cancer, meanwhile it could be a marker for differentiation that decreases in less differentiated tumors. As a tumor marker, K20 reflects inability to differentiate tumor type or grade in TCC, while in SCC of the bladder it is correlated with the grade. As a method, RT-PCR is superior to immunostaining for the detection of bladder cancer, meanwhile K20 immunohistochemistry ([HC) results were much better than urine cytology as a bladder cancer screening test. haematuria and inflammation reduced the specificity of telomerase assay, which reduced its validity as a tumor marker of bladder cancer. K 19 and K20 are the best candidates as screening tests for the diagnosis of bladder

  17. A Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy

    International Nuclear Information System (INIS)

    Purpose: To assess the long term efficacy of neoadjuvant MCV (Methotrexate, Cisplatin, Vinblastine) chemotherapy in patients with muscle invading bladder cancer treated by combined modality therapy with selection for consolidation by either cystectomy or Cisplatin and radiation (XRT) based on initial response. Patients and Methods: From 1990 through 1993, 126 patients (median age 68 years, range39 to 83 years) with clinical stage T2-T4aNXM0 bladder cancer were randomized following a thorough transurethral resection (TURBT), if possible, to receive (Arm 1, N=62) or not (Arm 2, N=64) 2 cycles of MCV prior to 39.6Gy pelvic irradiation with concurrent Cisplatin (100mg/M2) 2 courses, 3 weeks apart. Tumor response was scored as a clinical CR when the tumor-site biopsy and urine cytology were negative. The CR patients were treated with consolidation of an additional 25.2Gy to a total of 64.8Gy with 1 additional cycle of Cisplatin. Those with less than a CR were advised prompt cystectomy as were those with a subsequent invasive recurrence. The median follow up of surviving patients is 44 months. Results: 72% of patients completed the protocol with no or minor deviations; 62% on Arm 1 and 82% on Arm 2. The actuarial 5 year overall survival is 47%; 42% in Arm 1 and 50% in Arm 2. 40% of the patients had evidence of distant metastases at 5 years; 35% in Arm 1 and 43% in Arm 2. The 5 year survival with a functioning bladder is 36%, 32% in Arm 1, 39% in Arm 2. Among the 72 CR patients (60% CR in Arm 1 and 55% CR in Arm 2) 13% have had evidence of an invasive tumor relapse at 5 years. Six patients died during treatment; 5 in Arm 1, 1 in Arm 2. No patient required a cystectomy for treatment-related bladder morbidity. Conclusions: Two cycles of MCV neoadjuvant chemotherapy was not shown to provide an improved rate of CR to induction therapy or freedom from metastatic disease, or in five year overall survival. This absence of benefit in any of these endpoints may have resulted more

  18. Suppression of the PI3K pathway in vivo reduces cystitis-induced bladder hypertrophy and restores bladder capacity examined by magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Zhongwei Qiao

    Full Text Available This study utilized magnetic resonance imaging (MRI to monitor the real-time status of the urinary bladder in normal and diseased states following cyclophosphamide (CYP-induced cystitis, and also examined the role of the phosphoinositide 3-kinase (PI3K pathway in the regulation of urinary bladder hypertrophy in vivo. Our results showed that under MRI visualization the urinary bladder wall was significantly thickened at 8 h and 48 h post CYP injection. The intravesical volume of the urinary bladder was also markedly reduced. Treatment of the cystitis animals with a specific PI3K inhibitor LY294002 reduced cystitis-induced bladder wall thickening and enlarged the intravesical volumes. To confirm the MRI results, we performed H&E stain postmortem and examined the levels of type I collagen by real-time PCR and western blot. Inhibition of the PI3K in vivo reduced the levels of type I collagen mRNA and protein in the urinary bladder ultimately attenuating cystitis-induced bladder hypertrophy. The bladder mass calculated according to MRI data was consistent to the bladder weight measured ex vivo under each drug treatment. MRI results also showed that the urinary bladder from animals with cystitis demonstrated high magnetic signal intensity indicating considerable inflammation of the urinary bladder when compared to normal animals. This was confirmed by examination of the pro-inflammatory factors showing that interleukin (IL-1α, IL-6 and tumor necrosis factor (TNFα levels in the urinary bladder were increased with cystitis. Our results suggest that MRI can be a useful technique in tracing bladder anatomy and examining bladder hypertrophy in vivo during disease development and the PI3K pathway has a critical role in regulating bladder hypertrophy during cystitis.

  19. Prognostic impact of ReTURB in high grade T1 primary bladder cancer

    Directory of Open Access Journals (Sweden)

    Roberto Sanseverino

    2016-07-01

    Full Text Available Purpose: To evaluate whether pathological outcomes of ReTURB have a prognostic impact on recurrence and progression of primitive T1HG bladder cancer. Material and methods: Patients affected by primitive T1HG TCC of bladder underwent restaging TURB (ReTURB. Patients with muscle invasive disease at ReTURB underwent radical cystectomy; those with non-muscle invasive residual (NMI-RT and those with no residual tumour (NRT received an intravesical BCG therapy. We compared recurrence and progression in NMIRT patients and NRT patients at restaging TURB. Patients were followed every 3-6 months with cystoscopy and urine cytology. Results: 212 patients were enrolled in the study. At ReTURB, residual cancer was detected in 92 of 196 (46.9% valuable patients: 14.3% of these were upstaged to T2. At follow up of 26.3 ± 22.8 months, there were differences in recurrence and progression rates between NRT and NMIRT patients: 26.9% and 45.3% (p < 0.001, 10.6% and 23.4% (p 0.03, respectively. Recurrence-free and progression-free survivals were significantly higher in NRT compared to NMIRT patients: 73.1% and 54.7% (p < 0.001, 89.4% and 76.6 (p 0.03, respectively. Conclusions: ReTURB allows to identify a considerable number of residual and understaged cancer. Patients with NMIRT on ReTURB have worse prognosis than those with NRT in terms of recurrence and progression free survival. These outcomes seem to suggest a prognostic impact of findings on ReTURB that could be a valid tool in management of high grade T1 TCC.

  20. 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.

  1. Clinical implications in the shift of syndecan-1 expression from the cell membrane to the cytoplasm in bladder cancer

    International Nuclear Information System (INIS)

    To determine the diagnostic and prognostic capability of urinary and tumoral syndecan-1 (SDC-1) levels in patients with cancer of the urinary bladder. SDC-1 levels were quantitated by enzyme-linked immunosorbent assay (ELISA) in 308 subjects (102 cancer subjects and 206 non-cancer subjects) to assess its diagnostic capabilities in voided urine. The performance of SDC-1 was evaluated using the area under the curve of a receiver operating characteristic curve. In addition, immunohistochemical (IHC) staining assessed SDC-1 protein expression in 193 bladder specimens (185 cancer subjects and 8 non-cancer subjects). Outcomes were correlated to SDC-1 levels. Mean urinary levels of SDC-1 did not differ between the cancer subjects and the non-cancer subjects, however, the mean urinary levels of SDC-1 were reduced in high-grade compared to low-grade disease (p < 0.0001), and in muscle invasive bladder cancer (MIBC) compared to non-muscle invasive bladder cancer (NMIBC) (p = 0.005). Correspondingly, preliminary data note a shift from a membranous cellular localization of SDC-1 in normal tissue, low-grade tumors and NMIBC, to a distinctly cytoplasmic localization in high-grade tumors and MIBC was observed in tissue specimens. Alone urinary SDC-1 may not be a diagnostic biomarker for bladder cancer, but its urinary levels and cellular localization were associated with the differentiation status of patients with bladder tumors. Further studies are warranted to define the potential role for SDC-1 in bladder cancer progression

  2. 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

  3. 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

  4. 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

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

    DEFF Research Database (Denmark)

    Egerod, Frederikke N S Lihme; Bartels, Annette; Fristrup, Niels;

    2009-01-01

    BACKGROUND: Egr-1 (early growth response-1 transcription factor) has been proposed to be involved in invasion and metastasis processes of human bladder cancer, but Egr-1 protein expression levels in human bladder cancer have not been investigated. In the present study we investigated the expressi...

  6. 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

    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...... 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...

  7. Effect of Photodynamic Therapy with BPD-MA on the Proliferation and Apoptosis of Human Bladder Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Chuanshan Xu; Shiming Wu; Zhigang Wang; Lehua Yu; Qing Yang

    2005-01-01

    OBJECTIVE To explore the effect of photodynamic therapy with benzoporphyrin derivative monoacid ring A (BPD-MA) on the proliferation and apoptosis of human bladder cancer cells.METHODS Rhotosensitization of BPD-MA was activated with a red light laser (632.8 nm) delivered at 10 mw/cm2 to give a total dose of 2.4 J/cm2.Cellular proliferative activity was measured using the 3-(4,5-dimethylethiazil-2-yl)-2,5-Diph3-eyl tetrazolium bromide (MTT) assay and 3H-thymidine incorporation. Cell apoptosis was determined with flow cytometry analysis and the terminal deoxyuridine nicked-labeling (TUNEL) assay.RESULTS At 24 h post photodynamic treatment, photodynamic therapy significantly decreased cellular proliferative activity. The rate of apoptosis in BIU-87 cells 8 h after photodynamic treatment significantly increased up to 26.11± 2.59% as analyzed with flow cytometry. In situ labeling of DNA cleavage products with the terminal deoxyuridine nicked-labeling (TUNEL) assay reinforced these observations, BPD-MA-mediated photosensitization increased the number of TUNEL-positive cells compared to the controls. However, laser irradiation alone, BPD-MA alone and sham radiation did not affect cellular proliferative activity or apoptosis of the human bladder cancer BIU-87 cells.CONCLUSION Photodynamic therapy with BPD-MA significantly decreases cellular proliferative activity and enhances apoptosis. Therapy using this method might be a promising approach to treat patients with bladder cancer.

  8. 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

  9. 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.

  10. 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. PMID:27133452

  11. 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.

  12. Predictive factors for residual tumor and tumor upstaging on relook transurethral resection of bladder tumor in non-muscle invasive bladder cancer

    OpenAIRE

    Gill, Tejpal S.; Das, Ranjit K.; Supriya Basu; Dey, Ranjan K.; Subrata Mitra

    2014-01-01

    Context: Relook transurethral resection of bladder tumor (TURBT) improves the diagnostic and therapeutic efficacy of primary TURBT. However, it is still not established as to which category of patients would benefit most from this repeat invasive procedure. Aims: This prospective interventional study was designed to identify the category of patients with non-muscle invasive bladder cancer who may benefit from a routine relook procedure. Setting and Design: A total of 52 consecutive pa...

  13. A subclass of HER1 ligands are prognostic markers for survival in bladder cancer patients

    DEFF Research Database (Denmark)

    Thøgersen, Helle-Merete Vissing; Sørensen, B S; Poulsen, S S;

    2001-01-01

    Members of the epidermal growth factor (EGF) family have been suggested as prognostic markers in patients with bladder cancer. Thus far, there has been no consensus on their usefulness. We report an analysis of six ligands and two receptors of which a subset correlate to tumor stage and survival....... Biopsies from bladder cancer tumors were obtained from 73 patients followed for a median of 28 months. The mRNA content for six ligands [EGF, transforming growth factor alpha (TGF-alpha), amphiregulin (AR), betacellulin (betaCL), heparin-binding EGF-like growth factor (HB-EGF), epiregulin (EPI)] and two...

  14. Value of urinary topoisomerase-IIA cell-free DNA for diagnosis of bladder cancer

    OpenAIRE

    Kim, Ye-Hwan; Yan, Chunri; Lee, Il-Seok; Piao, Xuan-Mei; Byun, Young Joon; Jeong, Pildu; Kim, Won Tae; Yun, Seok-Joong; Kim, Wun-Jae

    2016-01-01

    Purpose Topoisomerase-II alpha (TopoIIA ), a DNA gyrase isoform that plays an important role in the cell cycle, is present in normal tissues and various human cancers, and can show altered expression in both. The aim of the current study was to examine the value of urinary TopoIIA cell-free DNA as a noninvasive diagnosis of bladder cancer (BC). Materials and Methods Two patient cohorts were examined. Cohort 1 (73 BC patients and seven controls) provided bladder tissue samples, whereas cohort ...

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

    OpenAIRE

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

    2016-01-01

    Background Despite being one of the most common cancers, bladder cancer is largely inefficiently and inaccurately staged and monitored. Current imaging methods detect cancer only when it has reached “visible” size and has significantly disrupted the structure of the organ. By that time, thousands of cells will have proliferated and perhaps metastasized. Repeated biopsies and scans are necessary to determine the effect of therapy on cancer growth. In this report, we describe a novel approach b...

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

    Directory of Open Access Journals (Sweden)

    Wei-Ching Lin

    2015-06-01

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

  17. 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

    2016-05-01

    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.

  18. Determinants of 4-aminobiphenyl-DNA adducts in bladder cancer biopsies.

    Science.gov (United States)

    Airoldi, Luisa; Orsi, Federica; Magagnotti, Cinzia; Coda, Renato; Randone, Donato; Casetta, Giovanni; Peluso, Marco; Hautefeuille, Agnes; Malaveille, Christian; Vineis, Paolo

    2002-05-01

    Exposure to 4-aminobiphenyl (4-ABP) is an important determinant of urinary bladder cancer in humans. We have analyzed by gas chromatography-mass spectrometry the DNA adducts of 4-ABP in 75 bladder cancer biopsies. The purpose was to understand whether smoking, N-acetyltransferase 2 (NAT2) polymorphism, diet or tumor grade were determinants of 4-ABP-DNA levels. 4-ABP-DNA adducts were above the detection limit of 0.1 fmol/microg DNA for 37/75 patients. Overall the level of adducts was 2.7 +/- 0.7 (mean +/- SE) fmol/microg DNA (86 +/- 22 adducts/10(8) normal nucleotides, mean +/- SE). A strong association with grade was observed. In the group of patients with detectable 4-ABP-DNA adducts the odds ratio for having a tumor grade of 2 or 3 was respectively 4.3 (95% CI 0.8-21.9) and 6 (1.3-27.5), compared with grade 1. A non-statistically significant association was found between adduct levels and the deduced slow acetylator phenotype in grades 2 and 3. The intake of fruit and vegetables produced a lower frequency of detectable adducts, though the association was not statistically significant. Detectable 4-ABP-DNA adducts were clearly associated with current smoking in higher tumor grades (grade 3 versus grades 1 + 2, odds ratios 10.4; 95% CI 1.7-63.1). Overall, our findings indicate that higher levels of DNA adducts characterize more invasive tumors (higher tumor grades). This seems to be facilitated by smoking and contrasted by the intake of fruit and vegetables. PMID:12016161

  19. Low dose intravesical heparin as prophylaxis against recurrent noninvasive (stage Ta) bladder cancer

    DEFF Research Database (Denmark)

    Bitsch, M; Hermann, G G; Andersen, J P;

    1990-01-01

    A controlled randomized clinical trial was conducted to examine the efficacy of topical low dose heparin (0.125 gm./l., 25,000 units per l.) as prophylaxis against recurrent noninvasive (stage Ta) transitional cell bladder cancer. Transurethral tumor resection was done with irrigation fluid...... containing either 1.5% glycine with heparin or glycine solution alone. Tumor recurrence was determined by cystoscopy 4 to 6 months later. There were 70 patients evaluated: 38 in the heparin and 32 in the control group, respectively. The recurrence rate (heparin 74%, control 66%) and the median number...... of recurrences (heparin 3, range 1 to 15 and control 3, range 1 to 30) were similar (p greater than 0.05) in the 2 groups of patients. These observations show that low dose heparin administered in the irrigation fluid during transurethral resection does not decrease the recurrence rate of noninvasive (stage Ta...

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

    Science.gov (United States)

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

    2009-07-15

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

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

    International Nuclear Information System (INIS)

    Arsenic toxicity is dependent on its chemical species. In humans, the bladder is one of the primary target organs for arsenic-induced carcinogenicity. However, little is known about the mechanisms underlying arsenic-induced carcinogenicity, and what arsenic species are responsible for this carcinogenicity. The present study aimed at comparing the toxic effect of DMMTAV with that of inorganic arsenite (iAsIII) on cell viability, uptake efficiency and production of reactive oxygen species (ROS) toward human bladder cancer EJ-1 cells. The results were compared with those of a previous study using human epidermoid carcinoma A431 cells. Although iAsIII was known to be toxic to most cells, here we show that iAsIII (LC50 = 112 μM) was much less cytotoxic than DMMTAV (LC50 = 16.7 μM) in human bladder EJ-1 cells. Interestingly, pentavalent sulfur-containing DMMTAV generated a high level of intracellular ROS in EJ-1 cells. However, this was not observed in the cells exposed to trivalent inorganic iAsIII at their respective LC50 dose. Furthermore, the presence of N-acetyl-cysteine completely inhibited the cytotoxicity of DMMTAV but not iAsIII, suggesting that production of ROS was the main cause of cell death from exposure to DMMTAV, but not iAsIII. Because the cellular uptake of iAsIII is mediated by aquaporin proteins, and because the resistance of cells to arsenite can be influenced by lower arsenic uptake due to lower expression of aquaporin proteins (AQP 3, 7 and 9), the expression of several members of the aquaporin family was also examined. In human bladder EJ-1 cells, mRNA/proteins of AQP3, 7 and 9 were not detected by reverse transcription polymerase chain reaction (RT-PCR)/western blotting. In A431 cells, only mRNA and protein of AQP3 were detected. The large difference in toxicity between the two cell lines could be related to their differences in uptake of arsenic species.

  2. 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

  3. Value of the dual phase 18F-FDG PET/CT with oral diuretic in the diagnosis of bladder cancer before therapy

    International Nuclear Information System (INIS)

    Background: PET with 18F-FDG has been considered of limited value for the detection of bladder cancer because of the urinary excretion of the tracer. Purpose: To investigate the clinical value of dual phase 18F-FDG PET/CT with oral diuretic in the diagnosis of bladder cancer. Methods: 107 patients with suspected bladder cancer were enrolled in the present study from May, 2003 to May, 2012. Each patient underwent the whole body 18F-FDG PET/CT scans routinely. After that, all patients received the forced diuresis by orally administration of furosemide (40 mg) and drinking a lot of water. Two hours later, after several times of urination, the patients underwent an additional delayed pelvic PET/CT scans. The intravesical radioactivity was compared between the routine and delayed the scans and the visualization of the tumor was evaluated. The diagnostic efficacy was determined based on the pathological examinations and the clinical following-up. Results: With the forced diuresis, intravesical 18F-FDG activity decreased significantly in 96.3% of the patients. The lesions on the wall of urinary bladder were visualized clearly in the delayed PET images, which weren't seen in the rout/ne PET images. 18F-FDG PET/CT was positive in 75 patients who all then received the operation. 69 patients were diagnosed pathologically to have the bladder cancer and 6 patients to have benign diseases. 18F-FDG PET/CT was negative in another 32 patients. Four patients of them were then diagnosed to be bladder cancer. Another 28 patients were clinically followed up more than 6 months and none of them was found to have bladder cancer. The sensitivity, specificity and accuracy of the dual phase PET/CT imaging for diagnosing the bladder cancer were 94.5%(69/73), 82.4%(28/34) and 90.7%(97/107), respectively. Conclusion: The forced diuresis using oral furosemide can significantly reduce the intravesical radioactivity and improve the detectability of 18F-FDG PET/CT for the bladder cancer

  4. Role of two single nucleotide polymorphisms in secreted frizzled related protein 1 and bladder cancer risk.

    Science.gov (United States)

    Rogler, Anja; Hoja, Sabine; Socher, Eileen; Nolte, Elke; Wach, Sven; Wieland, Wolf; Hofstädter, Ferdinand; Goebell, Peter J; Wullich, Bernd; Hartmann, Arndt; Stoehr, Robert

    2013-01-01

    In this study, we determined the genotype distribution of two single nucleotide polymorphisms (SNPs) in secreted frizzled related protein 1 (SFRP1), rs3242 and rs921142, in a Caucasian bladder cancer case-control study. Allelic variants of the SNPs were determined using restriction fragment length polymorphism (RFLP) analysis and partly verified by sequencing analysis. Overall, DNA from 188 consecutive and 215 early-onset bladder cancer patients (≤45 years) as well as from 332 controls was investigated. Potential microRNA binding sites were determined for rs3242, and microRNA expression was analysed in cell lines and tumour specimens. We observed a remarkable distribution difference in rs3242 between bladder cancer patients and healthy controls (p=0.05). Additionally, we found a significant difference in genotype distribution (p=0.032), resulting from the difference of early-onset patients and the control group (p=0.007). The risk allele T showed increased frequency in the early-onset patient group (p=0.002). Genotype-dependent differences of microRNA binding capacity were predicted in SFRP1 mRNA for two microRNAs. Hsa-miR-3646 showed strong expression in cell lines and tumour tissue, whereas hsa-miR-603 exhibited weak expression. The rs921142 SNP showed no significant association with bladder cancer risk. This is the first study to describe an association of the SFRP1 SNP rs3242 and bladder cancer risk as well as the influence of rs3242 on genotype-dependent microRNA capacity on SFRP1 mRNA. The onset of bladder seems to be associated with the increased occurrence of the T-allele in rs3242. PMID:24133576

  5. 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

  6. Pooled analysis and meta-analysis of glutathione S-transferase M1 and bladder cancer: A HuGE review

    DEFF Research Database (Denmark)

    Engel, Lawrence S.; Taioli, Emanuela; Pfeiffer, Ruth;

    2002-01-01

    Smoking is a known risk factor for bladder cancer. The product of the GSTM1 gene, glutathione S-transferase M1 (GSTM1), is involved in the detoxification of polycyclic aromatic hydrocarbons found in tobacco smoke; a homozygous deletion of this gene in approximately 50% of Caucasians and Asians...... that examined this association (17 studies, 2,149 cases, 3,646 controls) and excluded studies conducted in populations with a high prevalence of exposure to known bladder cancer risk factors other than tobacco smoke. Using random effects models in the meta-analysis, the authors obtained a summary odds ratio...... results in a lack of GSTM1 enzyme activity. Most studies examining the relation between bladder cancer and GSTM1 have reported an increased risk associated with a lack of GSTM1 activity. The authors performed meta- and pooled analyses of published and unpublished, case-control, genotype-based studies...

  7. Biopsies of the normal-appearing urothelium in primary bladder cancer

    Directory of Open Access Journals (Sweden)

    Davor Librenjak

    2010-01-01

    Full Text Available Aim: The aim of the study was to determine the incidence of "positive" findings in biopsies of the normal-appearing urothelium near primary cancer and their influence on therapeutic decisions. Materials and Methods: Between January 2001 and October 2008, in 230 patients with primary bladder cancer during initial resection of tumor, we also performed random biopsy of surrounding normal-appearing urothelium. We analyzed retrospectively the number and type of positive biopsy findings and their impact on further treatment. Results: There were 40% of patients (92/230 whose normal-appearing urothelium biopsy revealed pathological findings such as tumor tissue, Tis, and dysplasia. In 24.4% of patients, the stage of the primary tumor was Ta (32/131, in 50% it was T1 stage (30/61, and in 79% T2 stage (30/38. When we assessed the grade of malignancy, we found 18% of biopsies with G1 tumors (16/88, 33% with G2 tumors (19/59, and 69% with G3 tumors (57/83. Tumor tissue that was found in the normal-appearing urothelium in biopsy specimens in 13% of patients was in stage Ta (17/131, in 16% it was T1 stage (10/61, and in 39% of patients, the tumor was in T2 stage (15/38. Pathological findings of random biopsies were crucial in changing therapeutical decisions in 4.6% (9/192 of patients. Conclusion: Biopsy of the normal-appearing urothelial tissue is easy to perform and may help in identifying patients with high risk of disease progression and recurrence. Based on our results and results from the literature we recommend this simple tool as part of the routine management during transurethral resection of primary bladder cancer.

  8. A Systematic Overview of Radiation Therapy Effects in Urinary Bladder Cancer

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    Widmark, Anders; Flodgren, Per; Damber, Jan Erik; Hellsten, Sverker; Cavallin-Staahl, Eva [Univ. Hospital, Malmoe (Sweden). Dept. of Oncology

    2003-09-01

    A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately. This synthesis of the literature on radiation therapy for urinary bladder cancer is based on data from 3 meta-analyses and 33 randomized trials. The studies include 4,333 patients. The results were compared with those of a similar overview from 1996 including 15,042 patients. The conclusions reached can be summarized as these points: There is moderate evidence for an overall survival benefit with preoperative radiotherapy followed by cystectomy compared to curative radiotherapy based on early studies (1964-1986). Since that time surgical as well as radiation techniques have developed considerably. Therefore, the conclusion may not be relevant to modern treatment of invasive urinary bladder carcinoma. There is only one small study reporting on curative radiotherapy where increased dose per fraction is compared with conventionally fractionated radiotherapy to the same total dose. Thus, no conclusions can be drawn concerning optimal fraction dose. A meta-analysis based on two studies on hyperfractionated radiotherapy gives moderate evidence of a survival benefit at 5 and 10 years and an increased local control rate compared with conventional fractionation. The documentation of local control and overall survival rate after split-course radiation treatment compared to continuous therapy is conflicting. No firm conclusions can be drawn. Four small and early studies have compared radiation treatment using neutrons with photon treatment. The reports favour therapy with photons with respect to overall treatment results. There is moderate evidence for this conclusion. There is fairly strong evidence in early studies that radiation treatment in combination with hyperbaric oxygen does not confer a treatment benefit compared to radiation in

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

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    Mohamed Azza M

    2011-04-01

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

  10. 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.

  11. Municipal distribution of bladder cancer mortality in Spain: Possible role of mining and industry

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    Escolar-Pujolar Antonio

    2006-01-01

    Full Text Available Abstract Background Spain shows the highest bladder cancer incidence rates in men among European countries. The most important risk factors are tobacco smoking and occupational exposure to a range of different chemical substances, such as aromatic amines. Methods This paper describes the municipal distribution of bladder cancer mortality and attempts to "adjust" this spatial pattern for the prevalence of smokers, using the autoregressive spatial model proposed by Besag, York and Molliè, with relative risk of lung cancer mortality as a surrogate. Results It has been possible to compile and ascertain the posterior distribution of relative risk for bladder cancer adjusted for lung cancer mortality, on the basis of a single Bayesian spatial model covering all of Spain's 8077 towns. Maps were plotted depicting smoothed relative risk (RR estimates, and the distribution of the posterior probability of RR>1 by sex. Towns that registered the highest relative risks for both sexes were mostly located in the Provinces of Cadiz, Seville, Huelva, Barcelona and Almería. The highest-risk area in Barcelona Province corresponded to very specific municipal areas in the Bages district, e.g., Suría, Sallent, Balsareny, Manresa and Cardona. Conclusion Mining/industrial pollution and the risk entailed in certain occupational exposures could in part be dictating the pattern of municipal bladder cancer mortality in Spain. Population exposure to arsenic is a matter that calls for attention. It would be of great interest if the relationship between the chemical quality of drinking water and the frequency of bladder cancer could be studied.

  12. 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.

  13. Simple DVH parameter addition as compared to deformable registration for bladder dose accumulation in cervix cancer brachytherapy

    DEFF Research Database (Denmark)

    Andersen, Else Stougård; Noe, Karsten Østergaaard; Sørensen, Thomas Sangild;

    2013-01-01

    Background and purpose: Variations in organ position, shape, and volume cause uncertainties in dose assessment for brachytherapy (BT) in cervix cancer. The purpose of this study was to evaluate uncertainties associated with bladder dose accumulation based on DVH parameter addition (previously...... called "the worst case assumption") in fractionated BT. Materials and methods: Forty-seven patients treated for locally advanced cervical cancer were included. All patients received EBRT combined with two individually planned 3D image-guided adaptive BT fractions. D2 and D0.1 were estimated by DVH...

  14. Renal Papillary Necrosis Appearing as Bladder Cancer on Imaging.

    Science.gov (United States)

    Dagrosa, Lawrence M; Ghali, Fady; Gormley, Elizabeth Ann

    2016-01-01

    A 79-year-old woman with a history of diabetes mellitus and recurrent urinary tract infections (UTIs) presented with acute onset left lower quadrant pain, left-sided back pain, vomiting, and dysuria. Abdominopelvic CT scan revealed left hydroureteronephrosis to the level of the left ureterovesical junction (UVJ) where a bladder mass appeared to be obstructing the left ureteral orifice. The obstruction was ultimately found to be the result of a sloughed renal papilla lodged in the distal ureter, which created an inflammatory mass at the UVJ. Her history of diabetes and frequent UTIs likely predisposed her to the development of renal papillary necrosis (RPN) that resulted in sloughing of a renal papilla, distal ureteral obstruction with subsequent bladder inflammation that mimicked a bladder mass on imaging. RPN is a condition associated with many etiologies and likely represents a common final pathway of several diseases. Although several hypotheses exist, it is primarily thought to be ischemic in nature and is related to the underlying physiology of the renal papillae. We present a case of hydroureteronephrosis and bladder mass secondary to a sloughed renal papilla from RPN. PMID:27579408

  15. 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%) bladd...

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

    Science.gov (United States)

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

    1985-05-01

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

  17. 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.

  18. Evaluation of a Bladder Cancer Cluster in a Population of Criminal Investigators with the Bureau of Alcohol, Tobacco, Firearms and Explosives—Part 1: The Cancer Incidence

    Directory of Open Access Journals (Sweden)

    Susan R. Davis

    2012-01-01

    Full Text Available This study investigated a bladder cancer cluster in a cohort of employees, predominately criminal investigators, participating in a medical surveillance program with the United States Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF between 1995 and 2007. Standardized incidence ratios (SIRs were used to compare cancer incidences in the ATF population and the US reference population. Seven cases of bladder cancer (five cases verified by pathology report at time of analysis were identified among a total employee population of 3,768 individuals. All cases were white males and criminal investigators. Six of seven cases were in the 30 to 49 age range at the time of diagnosis. The SIRs for white male criminal investigators undergoing examinations were 7.63 (95% confidence interval = 3.70–15.75 for reported cases and 5.45 (2.33–12.76 for verified cases. White male criminal investigators in the ATF population are at statistically significant increased risk for bladder cancer.

  19. Long-term Outcomes in Treatment of Invasive Bladder Cancer With Concomitant Boost and Accelerated Hyperfractionated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Canyilmaz, Emine, E-mail: dremocan@yahoo.com [Department of Radiation Oncology, Karadeniz Technical University, Trabzon (Turkey); Yavuz, Melek Nur [Department of Radiation Oncology, Akdeniz University, Antalya (Turkey); Serdar, Lasif [Department of Radiation Oncology, Karadeniz Technical University, Trabzon (Turkey); Uslu, Gonca Hanedan; Zengin, Ahmet Yasar [Department of Radiation Oncology, Kanuni Research and Education Hospital, Trabzon (Turkey); Aynaci, Ozlem; Haciislamoglu, Emel; Bahat, Zumrut; Yoney, Adnan [Department of Radiation Oncology, Karadeniz Technical University, Trabzon (Turkey)

    2014-11-01

    Purpose: The aim of this study was to evaluate the long-term clinical efficacy and toxicity of concomitant boost and accelerated hyperfractionated radiation therapy (CBAHRT) in patients with invasive bladder cancer. Methods and Materials: Between October 1997 and September 2012, 334 patients with diagnoses of invasive bladder cancer were selected. These patients received CBAHRT as a bladder-conserving approach. The treatment consisted of a dose of 45 Gy/1.8 Gy to the whole pelvis with a daily concomitant boost of 1.5 Gy to the tumor. Total dose was 67.5 Gy in 5 weeks. A total of 32 patients (10.3%) had a diagnosis of stage T1, 202 (64.3%) were at stage T2, 46 (14.6%) were at stage T3a, 22 (7%) were at stage T3b, and 12 (3.8%) were at stage T4a. Results: The follow-up period was 33.1 months (range, 4.3-223.3 months). Grade 3 late intestinal toxicity was observed in 9 patients (2.9%), whereas grade 3 late urinary toxicity was observed in 8 patients (2.5%). The median overall survival (OS) was 26.3 months (95% confidence interval [CI]: 21.4-31.2). The 5-, 10, and 15-year OS rates were 32.1% (standard error [SE], ± 0.027), 17.9% (SE, ± 0.025) and 12.5% (SE, ± 0.028), respectively. The median cause-specific survival (CSS) was 42.1 months (95% CI: 28.7-55.5). The 5-, 10-, and 15-year CSS rates were 43.2% (SE, ± 0.03), 30.3% (SE, ± 0.03), and 28% (SE, ± 0.04), respectively. The median relapse-free survival (RFS) was 111.8 months (95% CI: 99.6-124). The 5-, 10-, and 15-year RFS rates were 61.9% (SE, ± 0.03), 57.6% (SE, ± 0.04), and 48.2% (SE, ± 0.07), respectively. Conclusions: The CBAHRT technique demonstrated acceptable toxicity and local control rates in patients with invasive bladder cancer, and this therapy facilitated bladder conservation. In selected patients, the CBAHRT technique is a practical alternative treatment option with acceptable 5-, 10-, and 15-year results in patients undergoing cystectomy as well as concurrent chemoradiation therapy.

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

    Directory of Open Access Journals (Sweden)

    Shingo Hatakeyama

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

  1. Expression of the Long Non-Coding RNA HOTAIR Correlates with Disease Progression in Bladder Cancer and Is Contained in Bladder Cancer Patient Urinary Exosomes.

    Directory of Open Access Journals (Sweden)

    Claudia Berrondo

    Full Text Available Exosomes are 30-150nM membrane-bound secreted vesicles that are readily isolated from biological fluids such as urine (UEs. Exosomes contain proteins, micro RNA (miRNA, messenger RNA (mRNA, and long non-coding RNA (lncRNA from their cells of origin. Although miRNA, protein and lncRNA have been isolated from serum as potential biomarkers for benign and malignant disease, it is unknown if lncRNAs in UEs from urothelial bladder cancer (UBC patients can serve as biomarkers. lncRNAs are > 200 nucleotide long transcripts that do not encode protein and play critical roles in tumor biology. As the number of recognized tumor-associated lncRNAs continues to increase, there is a parallel need to include lncRNAs into biomarker discovery and therapeutic target algorithms. The lncRNA HOX transcript antisense RNA (HOTAIR has been shown to facilitate tumor initiation and progression and is associated with poor prognosis in several cancers. The importance of HOTAIR in cancer biology has sparked interest in using HOTAIR as a biomarker and potential therapeutic target. Here we show HOTAIR and several tumor-associated lncRNAs are enriched in UEs from UBC patients with high-grade muscle-invasive disease (HGMI pT2-pT4. Knockdown of HOTAIR in UBC cell lines reduces in vitro migration and invasion. Importantly, loss of HOTAIR expression in UBC cell lines alters expression of epithelial-to-mesenchyme transition (EMT genes including SNAI1, TWIST1, ZEB1, ZO1, MMP1 LAMB3, and LAMC2. Finally, we used RNA-sequencing to identify four additional lncRNAs enriched in UBC patient UEs. These data, suggest that UE-derived lncRNA may potentially serve as biomarkers and therapeutic targets.

  2. 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.

  3. Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer.

    Science.gov (United States)

    Hojeij, Rim; Domingos-Pereira, Sonia; Nkosi, Marianne; Gharbi, Dalila; Derré, Laurent; Schiller, John T; Jichlinski, Patrice; Nardelli-Haefliger, Denise

    2016-01-01

    Bladder cancer is the second most common urological malignancy in the world. In 70% of cases it is initially diagnosed as non-muscle-invasive bladder cancer (NMIBC) and it is amenable to local treatments, with intravesical (IVES) Bacillus-Calmette-Guerin (BCG) immunotherapy being routinely used after transurethral resection of the lesion. However, this treatment is associated with significant side-effects and treatment failures, highlighting the necessity of novel strategies. One potent approach is the suicide-gene mediated therapy/prodrug combination, provided tumor-specificity can be ensured and anti-tumor immune responses induced. Using the mouse syngeneic orthotopic MB49-bladder tumor model, here we show that IVES human papillomavirus non-replicative pseudovirions (PsV) can pseudoinfect tumors with a ten-fold higher efficacy than normal bladders. In addition, PsV carrying the suicide-gene herpes-simplex virus thymidine kinase (PsV-TK) combined to Ganciclovir (GCV) led to immunogenic cell-death of tumor cells in vitro and to MB49-specific CD8 T-cells in vivo. This was associated with reduction in bladder-tumor growth and increased mice survival. Altogether, our data show that IVES PsV-TK/GCV may be a promising alternative or combinatory treatment for NMIBC. PMID:27428950

  4. Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Rim Hojeij

    2016-07-01

    Full Text Available Bladder cancer is the second most common urological malignancy in the world. In 70% of cases it is initially diagnosed as non-muscle-invasive bladder cancer (NMIBC and it is amenable to local treatments, with intravesical (IVES Bacillus-Calmette-Guerin (BCG immunotherapy being routinely used after transurethral resection of the lesion. However, this treatment is associated with significant side-effects and treatment failures, highlighting the necessity of novel strategies. One potent approach is the suicide-gene mediated therapy/prodrug combination, provided tumor-specificity can be ensured and anti-tumor immune responses induced. Using the mouse syngeneic orthotopic MB49-bladder tumor model, here we show that IVES human papillomavirus non-replicative pseudovirions (PsV can pseudoinfect tumors with a ten-fold higher efficacy than normal bladders. In addition, PsV carrying the suicide-gene herpes-simplex virus thymidine kinase (PsV-TK combined to Ganciclovir (GCV led to immunogenic cell-death of tumor cells in vitro and to MB49-specific CD8 T-cells in vivo. This was associated with reduction in bladder-tumor growth and increased mice survival. Altogether, our data show that IVES PsV-TK/GCV may be a promising alternative or combinatory treatment for NMIBC.

  5. 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

  6. 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

  7. HER-2/neu raises SHP-2, stops IFN-γ anti-proliferation in bladder cancer

    International Nuclear Information System (INIS)

    Gene amplification or HER-2/neu protein overexpression signals a poor outcome for bladder cancer patients. We investigated the anti-proliferative effect of IFN-γ in HER-2/neu-transfected human bladder cancer cells (TCC-N5 and TCC-N10). The cells continued growing after IFN-γ stimulation but did not activate the Janus kinase (Jak)/Stat pathway. We found Jak/Stat protein phosphatase in TCC-N5 and TCC-N10 cells with upregulated Src homology 2-containing protein tyrosine phosphatase-2 (SHP-2). After the cells had been treated with AG825, a HER-2/neu-specific inhibitor, SHP-2 expression declined, and Jak2/Stat1 reactivated. Similar results were reported in a mouse bladder cancer cell line, MBT2, with constitutive HER-2/neu overexpression. Further, AG825 pretreatment restored the anti-proliferation activity of IFN-γ in TCC-N5 and TCC-N10 cells. Therefore, the suppression of IFN-γ signaling in HER-2/neu-overexpressing bladder cancer cells might be due to SHP-2 upregulation. The regulation of SHP-2 by HER-2/neu provides a new target for blocking the HER-2/neu oncogenic pathway

  8. 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.

  9. 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.

  10. MOLECULAR MARKERS OF BLADDER CANCER: FROM THE PARTICULAR TO THE GENERAL

    OpenAIRE

    A. A. Zabolotneva; N. M. Gaifullin; A. A. Buzdin; B. Ya. Alekseyev; Yu. Yu. Andreyeva; P. V. Shegai; D. G. Sokov; I. G. Rusakov

    2011-01-01

    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.

  11. Molecular markers for urothelial bladder cancer prognosis: Toward implementation in clinical practice

    NARCIS (Netherlands)

    Rhijn, B.W. van; Catto, J.W.; Goebell, P.J.; Knuchel, R.; Shariat, S.F.; Poel, H.G. van der; Sanchez-Carbayo, M.; Thalmann, G.N.; Schmitz-Drager, B.J.; Kiemeney, L.A.L.M.

    2014-01-01

    OBJECTIVES: To summarize the current status of clinicopathological and molecular markers for the prediction of recurrence or progression or both in non-muscle-invasive and survival in muscle-invasive urothelial bladder cancer, to address the reproducibility of pathology and molecular markers, and to

  12. 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

  13. 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....

  14. 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.

  15. How to improve the effectiveness of transurethral resection in nonmuscle invasive bladder cancer?

    NARCIS (Netherlands)

    E.C.C. Cauberg; J.J.M.C.H. de la Rosette; Th.M. de Reijke

    2009-01-01

    Purpose of review The high rate of early recurrences in nonmuscle invasive bladder cancer is considered to be strongly related to the effectiveness of transurethral resection (TUR). The aim of this article is to review methods, currently available or in development, that aim at improving TUR, with a

  16. Penile Metastasis Secondary to Bladder Cancer: A Report of Two Cases

    OpenAIRE

    Narendra Kumar; Tapesh Bhattacharyya; Mandal, A K; Nalini Gupta; A Rajwanshi; Ritesh Kumar

    2014-01-01

    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.

  17. Adaptive radiotherapy for bladder cancer reduces integral dose despite daily volumetric imaging

    International Nuclear Information System (INIS)

    We studied the integral radiation dose in 27 patients who had adaptive radiotherapy for bladder cancer using kilo voltage cone beam CT imaging. Compared to conventional radiotherapy the reduction in margin and choice of best plan of three for the day resulted in a lower total dose in most patients despite daily volumetric imaging.

  18. Roles of ERβ and GPR30 in Proliferative Response of Human Bladder Cancer Cell to Estrogen

    Directory of Open Access Journals (Sweden)

    Weiren Huang

    2015-01-01

    Full Text Available Bladder cancer belongs to one of the most common cancers and is a leading cause of deaths in our society. Urothelial carcinoma of the bladder (UCB is the main type of this cancer, and the estrogen receptors in UCB remain to be studied. Our experiment aimed to investigate the possible biological effect of 17β-estradiol on human bladder-derived T24 carcinoma cells and to indicate its related mechanisms. T24 cells were treated with various doses of 17β-estradiol, and cell proliferation was detected using MTT assays. 17β-estradiol promoted T24 cell proliferation independent of ERβ/GPR30-regulated EGFR-MAPK pathway, while it inhibited cell growth via GPR30. Furthermore, the expression levels of downstream genes (c-FOS, BCL-2, and CYCLIN D1 were increased by 17β-estradiol and this effect was independently associated with activity of the EGFR-MAPK pathway. The two estrogen receptors might be potential therapeutic targets for the treatment of bladder cancer.

  19. 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...

  20. 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

  1. Suppression of the PI3K Pathway In Vivo Reduces Cystitis-Induced Bladder Hypertrophy and Restores Bladder Capacity Examined by Magnetic Resonance Imaging

    OpenAIRE

    Qiao, Zhongwei; Xia, Chunmei; Shen, Shanwei; Corwin, Frank D.; Liu, Miao; Guan, Ruijuan; John R. Grider; Qiao, Li-Ya

    2014-01-01

    This study utilized magnetic resonance imaging (MRI) to monitor the real-time status of the urinary bladder in normal and diseased states following cyclophosphamide (CYP)-induced cystitis, and also examined the role of the phosphoinositide 3-kinase (PI3K) pathway in the regulation of urinary bladder hypertrophy in vivo. Our results showed that under MRI visualization the urinary bladder wall was significantly thickened at 8 h and 48 h post CYP injection. The intravesical volume of the urinary...

  2. 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

  3. 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.

  4. 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.

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

    OpenAIRE

    L. V. Mirylenko; O. G. Sukonko; A. V. Pravorov; A. I. Rolevich; A. S. Mavrichev

    2014-01-01

    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 n...

  6. Genetic Variant as a Selection Marker for Anti–Prostate Stem Cell Antigen Immunotherapy of Bladder Cancer

    OpenAIRE

    Kohaar, Indu; Porter-Gill, Patricia; Lenz, Petra; Fu, Yi-Ping; Mumy, Adam; Tang, Wei; Apolo, Andrea B.; Rothman, Nathaniel; Baris, Dalsu; Schned, Alan R.; Ylaya, Kris; Schwenn, Molly; Johnson, Alison; Jones, Michael; Kida, Masatoshi

    2012-01-01

    A monoclonal antibody against prostate stem cell antigen (PSCA) has emerged as a novel cancer therapy currently being tested in clinical trials for prostate and pancreatic cancers, but this treatment is likely to be efficient only in patients with PSCA-expressing tumors. The present study demonstrates that a genetic variant (rs2294008) discovered by bladder cancer genome-wide association studies is a strong predictor of PSCA protein expression in bladder tumors, as measured by two-sided multi...

  7. N-Acetyltransferase 1 (NAT1) Genotype: A Risk Factor for Urinary Bladder Cancer in a Lebanese Population

    OpenAIRE

    Yassine, Ibrahim A.; Loulou Kobeissi; Jabbour, Michel E.; Dhaini, Hassan R

    2012-01-01

    In Lebanon, bladder cancer is the second most incident cancer among men. This study investigates a possible association between N-acetyltransferase 1 (NAT1) genotype, a drug-metabolizing enzyme coding gene, and bladder cancer in Lebanese men. A case-control study (54 cases and 105 hospital-based controls) was conducted in two major hospitals in Beirut. Cases were randomly selected from patients diagnosed in the period of 2002–2008. Controls were conveniently identified and selected from the s...

  8. Local bladder cancer clusters in southeastern Michigan accounting for risk factors, covariates and residential mobility.

    Directory of Open Access Journals (Sweden)

    Geoffrey M Jacquez

    Full Text Available In case control studies disease risk not explained by the significant risk factors is the unexplained risk. Considering unexplained risk for specific populations, places and times can reveal the signature of unidentified risk factors and risk factors not fully accounted for in the case-control study. This potentially can lead to new hypotheses regarding disease causation.Global, local and focused Q-statistics are applied to data from a population-based case-control study of 11 southeast Michigan counties. Analyses were conducted using both year- and age-based measures of time. The analyses were adjusted for arsenic exposure, education, smoking, family history of bladder cancer, occupational exposure to bladder cancer carcinogens, age, gender, and race.Significant global clustering of cases was not found. Such a finding would indicate large-scale clustering of cases relative to controls through time. However, highly significant local clusters were found in Ingham County near Lansing, in Oakland County, and in the City of Jackson, Michigan. The Jackson City cluster was observed in working-ages and is thus consistent with occupational causes. The Ingham County cluster persists over time, suggesting a broad-based geographically defined exposure. Focused clusters were found for 20 industrial sites engaged in manufacturing activities associated with known or suspected bladder cancer carcinogens. Set-based tests that adjusted for multiple testing were not significant, although local clusters persisted through time and temporal trends in probability of local tests were observed.Q analyses provide a powerful tool for unpacking unexplained disease risk from case-control studies. This is particularly useful when the effect of risk factors varies spatially, through time, or through both space and time. For bladder cancer in Michigan, the next step is to investigate causal hypotheses that may explain the excess bladder cancer risk localized to areas of

  9. The dual effects of polar methanolic extract of Hypericum perforatum L. in bladder cancer cells

    Science.gov (United States)

    Nseyo, U. O.; Nseyo, O. U.; Shiverick, K. T.; Medrano, T.; Mejia, M.; Stavropoulos, N.; Tsimaris, I.; Skalkos, D.

    2007-02-01

    Introduction and background: We have reported on the polar methanolic fraction (PMF) of Hypericum Perforatum L as a novel photosensitizing agent for photodynamic therapy (PDT) and photodynamic diagnosis (PDD). PMF has been tested in human leukemic cells, HL-60 cells, cord blood hemopoietic progenitor cells, bladder cancers derived from metastatic lymph node (T-24) and primary papillary bladder lesion (RT-4). However, the mechanisms of the effects of PMF on these human cell lines have not been elucidated. We have investigated mechanisms of PMF + light versus PMF-alone (dark experiment) in T-24 human bladder cancer cells. Methods: PMF was prepared from an aerial herb of HPL which was brewed in methanol and extracted with ether and methanol. Stock solutions of PMF were made in DSMO and stored in dark conditions. PMF contains 0.57% hypericin and 2.52% hyperforin. The T24 cell line was obtained from American Type Culture Collection (ATCC). In PDT treatment, PMF (60μg/ml) was incubated with cells, which were excited with laser light (630nm) 24 hours later. Apoptosis was determined by DNA fragmentation/laddering assay. DNA isolation was performed according to the manufacture's instructions with the Kit (Oncogene Kit#AM41). Isolated DNA samples were separated by electrophoresis in 1.5% in agarose gels and bands were visualized by ethidium bromide labeling. The initial cell cycle analysis and phase distribution was by flow cytometry. DNA synthesis was measured by [3H] thymidine incorporation, and cell cycle regulatory proteins were assayed by Western immunoblot. Results: The results of the flow cytometry showed PMF +light induced significant (40%) apoptosis in T24 cells, whereas Light or PMF alone produced little apoptosis. The percentage of cells in G 0/G I phase was decreased by 25% and in G2/M phase by 38%. The main impact was observed on the S phase which was blocked by 78% from the specific photocytotoxic process. DNA laddering analysis showed that PMF (60

  10. N1-guanyl-1,7-diaminoheptane sensitizes bladder cancer cells to doxorubicin by preventing epithelial-mesenchymal transition through inhibition of eukaryotic translation initiation factor 5A2 activation.

    Science.gov (United States)

    Yang, Jinsong; Yu, Haogang; Shen, Mo; Wei, Wei; Xia, Lihong; Zhao, Peng

    2014-02-01

    Drug resistance greatly reduces the efficacy of doxorubicin-based chemotherapy in bladder cancer treatment; however, the underlying mechanisms are poorly understood. We aimed to investigate whether N1-guanyl-1,7-diaminoheptane (GC7), which inhibits eukaryotic translation initiation factor 5A2 (eIF5A2) activation, exerts synergistic cytotoxicity with doxorubicin in bladder cancer, and whether eIF5A2 is involved in chemoresistance to doxorubicin-based bladder cancer treatment. BIU-87, J82, and UM-UC-3 bladder cancer cells were transfected with eIF5A2 siRNA or negative control siRNA before incubation with doxorubicin alone or doxorubicin plus GC7 for 48 h. Doxorubicin cytotoxicity was enhanced by GC7 in BIU-87, J82, and UM-UC-3 cells. It significantly inhibited activity of eIF5A2, suppressed doxorubicin-induced epithelial-mesenchymal transition in BIU-87 cells, and promoted mesenchymal-epithelial transition in J82 and UM-UC-3 cells. Knockdown of eIF5A2 sensitized bladder cancer cells to doxorubicin, prevented doxorubicin-induced EMT in BIU-87 cells, and encouraged mesenchymal-epithelial transition in J82 and UM-UC-3 cells. Combination therapy with GC7 may enhance the therapeutic efficacy of doxorubicin in bladder cancer by inhibiting eIF5A2 activation and preventing epithelial-mesenchymal transition.

  11. 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

  12. HMFG-2 as a prognostic indicator in superficial bladder cancer.

    OpenAIRE

    Conn, I G; Crocker, J.; Emtage, L A; Wallace, D M

    1988-01-01

    A series of transitional cell carcinomas and mucosal biopsy specimens of bladder were stained immunohistochemically with the monoclonal antibody HMFG-2. Staining characteristics ranged from luminal staining in well differentiated, superficial lesions to staining of all cells in invasive carcinomas. Invasive tumour nests also stained strongly with the antibody. There was good correlation between the staining pattern and histological assessment of both tumours and mucosal biopsy specimens. Corr...

  13. Loss of Maspin Expression in Bladder Cancer: Its Relationship with p53 and Clinico pathological Parameters

    International Nuclear Information System (INIS)

    Maspin (mammary serine protease inhibitor) is a member of the serpin super family of protease inhibitors and is known to have tumor-suppressor function in breast and prostate cancers, acting at the level of tumor invasion and metastasis. However, there have been no published data regarding the role of Maspin in squamous cell carcinoma (SCC) and transitional cell carcinoma (TCC) of urinary bladder. Patients and Methods: We have evaluated the immunohistochemical expression of Maspin and p53 in a series of 134 bladder cancer patients (56 SCC and 78 TCC) and the interrelationship between Clinico pathological features and Maspin and p53 expression. Results: There was positive Maspin expression in 53.7% in all cases. In TCC, expression was found in 48/78 cases (61.5%). High Maspin expression was found in low grade (p<0.001) and advanced stage (p=0.02). In SCC, expression was found in 24/56 (42.8%). There was a statistically significant association between lost Maspin expression and grading (p=0.001). No correlation was found between Maspin expression and other Clinico pathological parameters including gender, clinical stage and Bilharzial infestation. These results indicated that Maspin expression might predict a better prognosis for bladder carcinoma. Also Maspin probably could play a role in tumor progression. p53 was positive in 70 cases (52.2%) of all patients evaluated. In TCC, it was positive in 36/78 cases (46.1%) and correlated with high grade (p=0.01) and advanced stage (p=0.01). In SCC, it was positive in 34/56 cases (60.7%). There was a statistically significant association between p53 expression and high grade (p=0.01) and advanced stage (p=0.01). There was an inverse correlation between the Maspin and p53 expression in TCC and SCC of bladder cancer. We found no significant association between both Maspin and p53 expression and bilharziasis in TCC and SCC; this indicated that Maspin and p53 expression could be prognostic factors in both bilharzial and non

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

    NARCIS (Netherlands)

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

    2001-01-01

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

  15. Bladder cancer: The combination of chemotherapy and irradiation in the treatment of patients with muscle-invading tumors

    International Nuclear Information System (INIS)

    In the USA the recommended treatment for patients with muscle-invading transitional cell cancer of the bladder is usually radical cystectomy. Conservative surgery irradiation, and cisplatin-based systemic chemotherapy are, however, each effective for some patients. Although they provide the opportunity for bladder preservation, each modality, when used alone, is inferior to radical cystectomy in terms of local control and, perhaps, survival. Many recent publications have now documented the efficacy of combined modality treatment protocols employing all three of these modalities together. All employ a selective approach in which the patients only receive full-dose radiation if they have had a complete response to induction CMT. Overall survival data for T2-T3a patients are certainly as good as any reported cystectomy series of similarly clinically staged and similar aged patients. Radiation adds very significantly to the transurethral resection and systemic chemotherapy to maintain the bladder free of tumor. Substantially higher rates of pathologic confirmation of complete response are found following transurethral surgery and chemoradiation when compared with transurethral surgery and chemotherapy omitting the radiation. Overall survival is as good as cystectomy based approaches at 48-54% and over 80% of these long-term survivors keep their bladders. Following such therapies, 20-30% will subsequently develop superficial tumors. These patients may still be well treated by standard methods using transurethral resection and intravesical drugs. The concern of urologists that the conserved irradiated bladder functions poorly has also been answered by recent reports using modern radiation techniques. The instance of cystectomy for bladder shrinkage is repeatedly below 2%. Furthermore, sexual function is commonly preserved. The systemic morbidity of the chemotherapy is relatively high, but new approached using anti-emetics and GCSF now allow this to be reduced. In many

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

    Directory of Open Access Journals (Sweden)

    Mengyao Li

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

  17. Comparison of post contrast CT urography phases in bladder cancer detection

    International Nuclear Information System (INIS)

    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.)

  18. 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.)

  19. Effects of increasing carbon nanofiber density in polyurethane composites for inhibiting bladder cancer cell functions.

    Science.gov (United States)

    Tsang, Melissa; Chun, Young Wook; Im, Yeon Min; Khang, Dongwoo; Webster, Thomas J

    2011-07-01

    Polyurethane (PU) is a versatile elastomer that is commonly used in biomedical applications. In turn, materials derived from nanotechnology, specifically carbon nanofibers (CNFs), have received increasing attention for their potential use in biomedical applications. Recent studies have shown that the dispersion of CNFs in PU significantly enhances composite nanoscale surface roughness, tensile properties, and thermal stability. Although there have been studies concerning normal primary cell functions on such nanocomposites, there have been few studies detailing cancer cell responses. Since many patients who require bladder transplants have suffered from bladder cancer, the ideal bladder prosthetic material should not only promote normal primary human urothelial cell (HUC) function, but also inhibit the return of bladder cancerous cell activity. This study examined the correlation between transitional (UMUC) and squamous (or SCaBER) urothelial carcinoma cells and HUC on PU:CNF nanocomposites of varying PU and CNF weight ratios (from pure PU to 4:1 [PU:CNF volume ratios], 2:1, 1:1, 1:2, and 1:4 composites to pure CNF). Composites were characterized for mechanical properties, wettability, surface roughness, and chemical composition by atomic force microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and goniometry. The adhesion and proliferation of UMUC and SCaBER cancer cells were assessed by MTS assays. Cellular responses were further quantified by measuring the amounts of nuclear mitotic protein 22 (NMP-22), vascular endothelial growth factor (VEGF), and tumor necrosis factor alpha. Results demonstrated that both UMUC and SCaBER cell proliferation rates decreased over time on substrates with increased CNF in PU. In addition, with the exception of VEGF from UMUC (which was the same across all materials), composites containing the most CNF activated cancer cells (UMUC and SCaBER) the least, as shown by

  20. 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.

  1. 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.

  2. 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

  3. Psychological Disorders and Psychosocial Resources of Patients with Newly Diagnosed Bladder and Kidney Cancer: A Cross-Sectional Study.

    Directory of Open Access Journals (Sweden)

    Yi-Long Yang

    Full Text Available Psychological disorders have been proven to be associated with poor physiological, psychological and immune outcomes in cancer patients. However, despite of many challenges of the changed self-image/body image and the altered sexual/urinary function, relatively little is known about psychological disorders of patients with newly diagnosed bladder and kidney cancer. We aimed to investigate the prevalence of depression, anxiety, post-traumatic stress disorder (PTSD and the associated psychosocial factors among bladder/kidney cancer patients.A cross-sectional study was conducted of consecutive inpatients with bladder/kidney cancer in the First Affiliated Hospital of China Medical University in Liaoning Province, northeast China. A total of 489 early-stage cancer patients eligible for this study completed questionnaires on demographic and clinical variables, depression, anxiety, PTSD, perceived social support and positive psychological variables (hope, optimism and resilience anonymously during October 2013 and August 2014. Hierarchical regression analysis was used to examine the relationships between psychosocial resources and psychological disorders, while controlling for possible covariates.The prevalence of depression, anxiety and PTSD was 77.5%, 69.3% and 25.2%, respectively, while 24.9% of patients had psychological co-morbidity. Psychosocial resources together explained more than one-third of the variance on psychological disorders. Under standardized estimate (β sequence, patient's perception of social support from family was significantly associated with depression, anxiety and PTSD (p < 0.01. Optimism and resilience showed integrated and independent effects on psychological disorders, and hope represented the significant association with PTSD only (p < 0.01.The high prevalence of psychological disorders in newly diagnosed patients with early-stage bladder/kidney cancer should receive more attention in Chinese medical settings

  4. 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

    were analyzed using monoclonal antibodies against T cells, natural killer (NK) -cells, monocytes, and activation markers. The cytotoxicities of US-PBMC, PS-PBMC, and LAK cells were all significantly lower in the cancer patients than in the controls (P less than 0.05). The percentages of PBMC positive......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...

  5. 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

  6. Curcumin Promotes KLF5 Proteasome Degradation through Downregulating YAP/TAZ in Bladder Cancer Cells

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. 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

  9. Distinct SNP combinations confer susceptibility to urinary bladder cancer in smokers and non-smokers.

    Science.gov (United States)

    Schwender, Holger; Selinski, Silvia; Blaszkewicz, Meinolf; Marchan, Rosemarie; Ickstadt, Katja; Golka, Klaus; Hengstler, Jan G

    2012-01-01

    Recently, genome-wide association studies have identified and validated genetic variations associated with urinary bladder cancer (UBC). However, it is still unknown whether the high-risk alleles of several SNPs interact with one another, leading to an even higher disease risk. Additionally, there is no information available on how the UBC risk due to these SNPs compare to the risk of cigarette smoking and to occupational exposure to urinary bladder carcinogens, and whether the same or different SNP combinations are relevant in smokers and non-smokers. To address these questions, we analyzed the genotypes of six SNPs, previously found to be associated with UBC, together with the GSTM1 deletion, in 1,595 UBC cases and 1,760 controls, stratified for smoking habits. We identified the strongest interactions of different orders and tested the stability of their effect by bootstrapping. We found that different SNP combinations were relevant in smokers and non-smokers. In smokers, polymorphisms involved in detoxification of cigarette smoke carcinogens were most relevant (GSTM1, rs11892031), in contrast to those in non-smokers with MYC and APOBEC3A near polymorphisms (rs9642880, rs1014971) being the most influential. Stable combinations of up to three high-risk alleles resulted in higher odds ratios (OR) than the individual SNPs, although the interaction effect was less than additive. The highest stable combination effects resulted in an OR of about 2.0, which is still lower than the ORs of cigarette smoking (here, current smokers' OR: 3.28) and comparable to occupational carcinogen exposure risks which, depending on the workplace, show mostly ORs up to 2.0.

  10. Distinct SNP combinations confer susceptibility to urinary bladder cancer in smokers and non-smokers.

    Directory of Open Access Journals (Sweden)

    Holger Schwender

    Full Text Available Recently, genome-wide association studies have identified and validated genetic variations associated with urinary bladder cancer (UBC. However, it is still unknown whether the high-risk alleles of several SNPs interact with one another, leading to an even higher disease risk. Additionally, there is no information available on how the UBC risk due to these SNPs compare to the risk of cigarette smoking and to occupational exposure to urinary bladder carcinogens, and whether the same or different SNP combinations are relevant in smokers and non-smokers. To address these questions, we analyzed the genotypes of six SNPs, previously found to be associated with UBC, together with the GSTM1 deletion, in 1,595 UBC cases and 1,760 controls, stratified for smoking habits. We identified the strongest interactions of different orders and tested the stability of their effect by bootstrapping. We found that different SNP combinations were relevant in smokers and non-smokers. In smokers, polymorphisms involved in detoxification of cigarette smoke carcinogens were most relevant (GSTM1, rs11892031, in contrast to those in non-smokers with MYC and APOBEC3A near polymorphisms (rs9642880, rs1014971 being the most influential. Stable combinations of up to three high-risk alleles resulted in higher odds ratios (OR than the individual SNPs, although the interaction effect was less than additive. The highest stable combination effects resulted in an OR of about 2.0, which is still lower than the ORs of cigarette smoking (here, current smokers' OR: 3.28 and comparable to occupational carcinogen exposure risks which, depending on the workplace, show mostly ORs up to 2.0.

  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

    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. Hedyotis diffusa plus Scutellaria barbata Induce Bladder Cancer Cell Apoptosis by Inhibiting Akt Signaling Pathway through Downregulating miR-155 Expression

    OpenAIRE

    Li-Tao Pan; Yip Sheung; Wen-Peng Guo; Zhi-Bin Rong; Zhi-Ming Cai

    2016-01-01

    Traditional Chinese medicine is increasingly used to treat cancer. Our clinical experiences identify Hedyotis diffusa plus Scutellaria barbata as the most common herb-pair (couplet medicinal) used for the core treatment of bladder cancer. This study aims to investigate the antitumor effect of the herb-pair in bladder cancer cells. The results show that Hedyotis diffusa plus Scutellaria barbata inhibited bladder cancer cell growth and clone formation in a dose-dependent and time-dependent mann...

  13. Molecular Detection of Bladder Cancer by Fluorescence Microsatellite Analysis and an Automated Genetic Analyzing System

    Directory of Open Access Journals (Sweden)

    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.

  14. A rare bladder cancer - small cell carcinoma: review and update

    Directory of Open Access Journals (Sweden)

    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.

  15. Expression of the Long Non-Coding RNA HOTAIR Correlates with Disease Progression in Bladder Cancer and Is Contained in Bladder Cancer Patient Urinary Exosomes

    OpenAIRE

    Berrondo, Claudia; Flax, Jonathan; Kucherov, Victor; Siebert, Aisha; Osinski, Thomas; Rosenberg, Alex; Fucile, Christopher; Richheimer, Samuel; Beckham, Carla J.

    2016-01-01

    Exosomes are 30-150nM membrane-bound secreted vesicles that are readily isolated from biological fluids such as urine (UEs). Exosomes contain proteins, micro RNA (miRNA), messenger RNA (mRNA), and long non-coding RNA (lncRNA) from their cells of origin. Although miRNA, protein and lncRNA have been isolated from serum as potential biomarkers for benign and malignant disease, it is unknown if lncRNAs in UEs from urothelial bladder cancer (UBC) patients can serve as biomarkers. lncRNAs are > 200...

  16. Epidemiological factors in gall bladder cancer in eastern India-a single centre study.

    Science.gov (United States)

    Khan, Imran; Panda, Nilanjan; Banerjee, Manju; Das, Ruchira

    2013-03-01

    India has high incidence of Gallbladder carcinoma with regional variation in incidence possibly due to environmental factors. Prospective study of all the gall bladder cancer in our hospital over 18 months analysing how the epidemiological factors are influencing the disease. Incidence-Four cases per 100,000 populations per year. The peak incidence was in 41 to 50 years group (49.20 %). Male to female ratio was 1:3.8. Majority (69.84 %) were in lower socio-economic group. 61 out of 63 patients (96.62 %) were non-vegetarians. 60.34 % and 19.04 % patients weighed between 50 and 55 kg and 55and 60 kg respectively (p = 0.003). Male smokers had significantly higher risk (p = 0.000 1). Gall stones were present in 45 out of 63 cases(71.42 %).45 out of 63 patients were typhoid carriers (p < 0.05). Pain abdomen was the commonest complaint (87.30 %), followed by pallor, lump in right upper quadrant, nausea & vomiting and jaundice in 71.42 %, 69.84 %, 66.66 %, 31.74 % patients respectively. This data highlights high prevalence of gall bladder carcinoma in Eastern India. Better hygiene and water supply to prevent typhoid carriers, prevention of malnutrition, early intervention for cholelithiasis, importance of balanced diet, increase in awareness about risk of tobacco and alcohol consumption-all are highlighted as significant modifiable factors. PMID:24426702

  17. Vitamin C and E intake and risk of bladder cancer: a meta-analysis of observational studies

    OpenAIRE

    Wang, Yu-Yong; Wang, Xu-Liang; Yu, Zhi-jian

    2014-01-01

    Epidemiologic studies that investigate whether vitamin C and E intake protects against bladder cancer have yielded inconsistent results. We conducted a systematic review and meta-analysis of published cohort and case-control studies to summarize the epidemiologic evidence investigating vitamin C and E intake and bladder cancer. Studies were identified through a search of PubMed and Embase databases and of references from relevant publications. Meta-analyses were conducted to estimate summary ...

  18. Personal use of hair dyes and the risk of bladder cancer: results of a meta-analysis.

    OpenAIRE

    Huncharek, Michael; Kupelnick, Bruce

    2005-01-01

    OBJECTIVE: This study examined the methodology of observational studies that explored an association between personal use of hair dye products and the risk of bladder cancer. METHODS: Data were pooled from epidemiological studies using a general variance-based meta-analytic method that employed confidence intervals. The outcome of interest was a summary relative risk (RRs) reflecting the risk of bladder cancer development associated with use of hair dye products vs. non-use. Sensitivity analy...

  19. 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.

  20. Evaluation of the response chemotherapy for penile metastasis of bladder cancer using 18F-fluorodeoxyglucose-PET/CT

    OpenAIRE

    Hakan Öztürk

    2015-01-01

    Background: Metachronous penile metastasis of bladder cancer occurs very rarely. The clinical management of the disease involves complex problems, and the disease is associated with a poor prognosis. The common mode of spread to the penis is by the retrograde venous route. Patients and methods: A 68-year-old patient who was diagnosed with invasive bladder cancer underwent 18F-fluorodeoxyglucose (FDG)-positron-emission tomography/computed tomography (PET/CT) for staging purposes. An 18 mm i...

  1. Glutathione S-transferase T1, O1 and O2 polymorphisms are associated with survival in muscle invasive bladder cancer patients.

    Directory of Open Access Journals (Sweden)

    Tatjana I Djukic

    Full Text Available OBJECTIVE: To examine the association of six glutathione transferase (GST gene polymorphisms (GSTT1, GSTP1/rs1695, GSTO1/rs4925, GSTO2/rs156697, GSTM1, GSTA1/rs3957357 with the survival of patients with muscle invasive bladder cancer and the genotype modifying effect on chemotherapy. PATIENTS AND METHODS: A total of 105 patients with muscle invasive bladder cancer were included in the study. The follow-up lasted 5 years. The effect of GSTs polymorphisms on predicting mortality was analyzed by the Cox proportional hazard models, while Kaplan-Meier analysis was performed to assess differences in survival. RESULTS: GSTT1 active, GSTO1 Asp140Asp or GSTO2 Asp142Asp genotypes were independent predictors of a higher risk of death among bladder cancer patients (HR = 2.5, P = 0.028; HR = 2.9, P = 0.022; HR = 3.9, P = 0.001; respectively and significantly influenced the overall survival. There was no association between GSTP1, GSTM1 and GSTA1 gene variants with overall mortality. Only GSTO2 polymorphism showed a significant effect on the survival in the subgroup of patients who received chemotherapy (P = 0.006. CONCLUSION: GSTT1 active genotype and GSTO1 Asp140Asp and GSTO2 Asp142Asp genotypes may have a prognostic/pharmacogenomic role in patients with muscle invasive bladder cancer.

  2. Polymorphisms in the XPC gene affect urinary bladder cancer risk: a case-control study, meta-analyses and trial sequential analyses.

    Science.gov (United States)

    Sankhwar, Monica; Sankhwar, Satya Narayan; Bansal, Sandeep Kumar; Gupta, Gopal; Rajender, Singh

    2016-01-01

    Compromised activity of the DNA repair enzymes may raise the risk of a number of cancers. We analyzed polymorphisms in the Xeroderma Pigmentosum, Complementation Group C (XPC) gene for their correlation with urinary bladder cancer. Ala499Val and Lys939Gln polymorphisms were genotyped in 234 urinary bladder cancer cases and 258 control samples. A significant association between Ala499Val polymorphism and bladder cancer was observed (OR = 1.78, CI = 1.19-2.66, p = 0.005); however, Lys939Gln was unrelated (OR = 0.97, CI = 0.65-1.45, P = 0.89). Further analysis revealed that Ala499Val was a significant risk factor only in the presence of smoking (OR = 2.23, CI = 1.28-3.87, p < 0.004) or tobacco chewing (OR = 2.40, CI = 1.43-4.04, p = 0.0008). To further appraise the association, we undertook meta-analyses on seven studies (2893 cases and 3056 controls) on Ala499Val polymorphism and eleven studies (5064 cases and 5208 controls) on Lys939Gln polymorphism. Meta-analyses corroborated the above results, showing strong association of Ala499Val (OR = 1.54, CI = 1.21-1.97, p = 0.001) but not that of Lys939Gln (OR = 1.13, CI = 0.95-1.34, p = 0.171) with urinary bladder cancer risk. In conclusion, XPC Ala499Val substitution increases urinary bladder cancer risk, but Lys939Gln appears to be neutral. PMID:27246180

  3. 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.

  4. Bladder cancer risk in painters: a review of the epidemiological evidence, 1989-2004.

    Science.gov (United States)

    Bosetti, Cristina; Pira, Enrico; La Vecchia, Carlo

    2005-11-01

    Epidemiological studies on the potential association between painting and the risk of bladder cancer published after the Monograph of the International Agency for Research on Cancer N. 47 of 1989 have been systematically reviewed. These included four cohort studies on the incidence of bladder cancer among painters, with a pooled relative risk (RR) of 1.10 (95% confidence interval, CI, 1.03-1.18), based on 893 cases observed. The corresponding summary RR from four cohort studies on mortality was 1.23 (95% CI 1.11-1.37), based on 370 deaths. The pooled RR from 14 case-control studies and a pooled-analysis of other 11 case-control studies was 1.35 (95% CI 1.19-1.53), based on 465 cases exposed. Overall, the RR from all epidemiological studies was 1.17 (95% 1.11-1.27). Thus, recent epidemiological evidence indicates a moderate excess risk for bladder cancer in painters. Some studies, however, suggested that any such risk would have been greater for exposures in the distant past. Open issues for interpretation include residual confounding by social class and tobacco smoking, and understanding the time-risk relation. In particular, the potential residual risk related to exposure over the last two to three decades remains to be defined. PMID:16184465

  5. 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.

  6. The preliminary result of a prospective study of bladder conserving treatment using transurethral resection, transarterial chemotherapy and local involved field radiotherapy in invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nagano, Hisato; Nagata, Maki; Yamaguchi, Yoshio; Nagashima, Toshiyuki; Tanohata, Kazunori [Yokohama Rosai Hospital (Japan)

    2002-12-01

    Radical cystectomy has been a standard treatment for invasive urinary bladder cancer, however preservation therapy is being considered in many facilities as a clinical examination. After transurethral resection of the bladder (TUR-Bt), three-time transarterial infusion (TAI) of cisplatin (CDDP) 45 mg/m{sup 2}, methotrexate (MTX) 30 mg/m{sup 2} and local five-port external beam radiation therapy (EBRT) of 60 Gy/30 fx/ 6 wks were delivered concurrently. Because such reports of organ sparing treatment using TAI are few, a mono-arm prospective study was designed to evaluate the rate of complete response (CR) (Response Evaluation Criteria In Solid Tumor (RECIST) standard) and the incidence of acute toxicity (National Cancer Institute (NCI) standard) compared with previous reports in which intravenous chemotherapy was used in a tri-modality treatment protocol. Twenty-three patients with T{sub 2-4}N{sub 0}M{sub 0} or High risk T{sub 1}N{sub 0}M{sub 0} were registered (T{sub 1}; 7, T{sub 2}; 7, T{sub 3}; 8, T{sub 4}; 1). They were all in good performance status (PS) (0-1). CR rate after intravesical therapy with bacilli Calmette-Guerin (BCG) was eighty-seven percent (confidence interval (CI) 66-97%). There was a significant difference (p=0.03) between this value and that (CR rate=62%, n=299) calculated from two reports in which transvenous chemotherapy was used as one of the treatment modalities. Grade three white blood cell decrease was seen in twenty-six percent of patients. This was significantly higher than the value estimated from reports using cisplatin only as the single chemotherapy agent. An acute reaction of the urinary bladder and rectum was negligible. After fifteen-month follow-up, four patients relapsed and two showed metastatic lesions. According to the protocol, three of the former four had already received cystectomy, but one had undergone an intra-vesicle BCG injection because it showed non-invasive papillary histology, and reached CR again. M

  7. A Pilot Study on the Potential of RNA-Associated to Urinary Vesicles as a Suitable Non-Invasive Source for Diagnostic Purposes in Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Perez, Amparo; Loizaga, Ana; Arceo, Raquel; Lacasa, Isabel; Rabade, Ainara [Urology Service, Basurto University Hospital, Bilbao 48013, Bizkaia (Spain); Zorroza, Kerman [Basque Foundation for Health Innovation and Research (BIOEF), DNA Laboratory, Basurto Hospital, Bilbao 48013, Bizkaia (Spain); Mosen-Ansorena, David [Genome Analysis Platform, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio 48160, Bizkaia (Spain); Gonzalez, Esperanza [Metabolomics Unit, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio 48160, Bizkaia (Spain); Aransay, Ana M. [Genome Analysis Platform, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio 48160, Bizkaia (Spain); Falcon-Perez, Juan M. [Metabolomics Unit, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio 48160, Bizkaia (Spain); IKERBASQUE, Basque Foundation for Science, Bilbao 48011, Bizkaia (Spain); Unda-Urzaiz, Miguel [Urology Service, Basurto University Hospital, Bilbao 48013, Bizkaia (Spain); Royo, Felix, E-mail: froyo.ciberehd@cicbiogune.es [Metabolomics Unit, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio 48160, Bizkaia (Spain)

    2014-01-22

    Bladder cancer is one of the most common cancers and, together with prostate carcinoma, accounts for the majority of the malignancies of the genitourinary tract. Since prognosis ameliorates with early detection, it will be beneficial to have a repertoire of diagnostic markers that could complement the current diagnosis protocols. Recently, cell-secreted extracellular vesicles have received great interest as a source of low invasive disease biomarkers because they are found in many body fluids, including urine. The current work describes a pilot study to generate an array-based catalogue of mRNA associated to urinary vesicles, and also a comparison with samples obtained from bladder cancer patients. After an analysis of presence/absence of transcripts in bladder cancer EVs, a list of genes was selected for further validation using PCR technique. We found four genes differentially expressed in cancer samples. LASS2 and GALNT1 were present in cancer patients, while ARHGEF39 and FOXO3 were found only in non-cancer urinary vesicles. Previous studies have pointed to the involvement of those genes in tumour progression and metastasis.

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

    Energy Technology Data Exchange (ETDEWEB)

    Bingsong Lei; Xiaoyuan Deng; Huajiang Wei; Zhouyi Guo [MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, Guangdong Province (China); Guoyong Wu [Department of Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong Province (China); Hongqin Yang; Shusen Xie [Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education of China, Fujian Normal University, Fuzhou 350007, Fujian (China); Yonghong He [Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, Guangdong (China)

    2014-12-31

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

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

    International Nuclear Information System (INIS)

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

  10. 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 review summarizes the current understanding of the BCG-induced macrophage cytotoxicity toward bladder cancer cells with an intention to inspire investigation on this important but underdeveloped research field.

  11. Plasmacytoid variant of bladder cancer defines patients with poor prognosis if treated with cystectomy and adjuvant cisplatin-based chemotherapy

    Directory of Open Access Journals (Sweden)

    Keck Bastian

    2013-02-01

    Full Text Available Abstract Background Since the definition of different histologic subtypes of urothelial carcinomas by the World Health Organization (WHO 2004 classification, description of molecular features and clinical behavior of these variants has gained more attention. Methods We reviewed 205 tumor samples of patients with locally advanced bladder cancer mainly treated within the randomized AUO-AB05/95 trial with radical cystectomy and adjuvant cisplatin-based chemotherapy for histologic subtypes. 178 UC, 18 plasmacytoid (PUC and 9 micropapillary (MPC carcinomas of the bladder were identified. Kaplan Meier analysis and backward multivariate Cox’s proportional hazards regression analysis were performed to compare overall survival between the three histologic subtypes. Results Patients suffering from PUC have the worst clinical outcome regarding overall survival compared to conventional UC and MPC of the bladder that in turn seem have to best clinical outcome (27.4 months, 62.6 months, and 64.2 months, respectively; p=0.013 by Kaplan Meier analysis. Backward multivariate Cox´s proportional hazards regression analysis (adjusted to relevant clinicopathological parameters showed a hazard ratio of 3.2 (p=0.045 for PUC in contrast to patients suffering from MPC. Conclusions Histopathological diagnosis of rare variants of urothelial carcinoma can identify patients with poor prognosis.

  12. Plasmacytoid variant of bladder cancer defines patients with poor prognosis if treated with cystectomy and adjuvant cisplatin-based chemotherapy

    International Nuclear Information System (INIS)

    Since the definition of different histologic subtypes of urothelial carcinomas by the World Health Organization (WHO) 2004 classification, description of molecular features and clinical behavior of these variants has gained more attention. We reviewed 205 tumor samples of patients with locally advanced bladder cancer mainly treated within the randomized AUO-AB05/95 trial with radical cystectomy and adjuvant cisplatin-based chemotherapy for histologic subtypes. 178 UC, 18 plasmacytoid (PUC) an