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Sample records for bladder cancer 3

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

    OpenAIRE

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

    2014-01-01

    The transcription factor GATA3 is known as a breast tumor suppressor as well as a urothelial marker, and its loss is often seen in high-grade invasive bladder cancer. Nonetheless, GATA3 functions in bladder cancer cells remain largely unknown. In this study, we assessed the effects of GATA3 silencing via RNA interference on cell migration, invasion, and proliferation of bladder cancer. GATA3 expression was downregulated in all four bladder cancer lines examined, compared with a non-neoplastic...

  2. Bladder Cancer Advocacy Network

    Science.gov (United States)

    ... future bladder cancer research through the Patient Survey Network. Read More... Don’t Miss the 2016 BCAN ... Click here for more details Bladder Cancer Advocacy Network 4915 St. Elmo Avenue, Suite 202 Bethesda, Maryland ...

  3. Treatment Option Overview (Bladder Cancer)

    Science.gov (United States)

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

  4. Management of invasive bladder cancer

    International Nuclear Information System (INIS)

    Muscle invasive disease accounts for a quarter of all cases of bladder cancer. A bewildering variety of treatment options are available for patients with this disease, with combinations of surgery and/or radiotherapy, with or without chemotherapy. This review discusses these treatment options and their relative merits for patients with muscle invasive bladder cancer. 22 refs., 3 figs., 7 tabs

  5. 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, ...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    Highlights: → Oct3/4-positive cells increase in Schistosoma haematobium (SH)-associated bladder cancer. → iNOS-dependent DNA lesion, 8-nitroguanine, was formed in Oct3/4-positive cells. → 8-Nitroguanine formed in stem-like cells plays a role in SH-induced carcinogenesis. → 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-κB (NF-κB) 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-κB 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-κB activation, leading to tumor development.

  8. Origins of Bladder Cancer.

    Science.gov (United States)

    Czerniak, Bogdan; Dinney, Colin; McConkey, David

    2016-05-23

    Bladder cancer, one of the most frequently occurring human cancers, develops via two tracks referred to as papillary and nonpapillary that correspond to clinically different forms of the disease. Most bladder cancers are chemically induced, with tobacco smoking being the leading risk factor. Recent advances in bladder cancer research have enhanced our understanding of the origin of this disease from urothelial progenitor cells via field effects along papillary/luminal and nonpapillary/basal pathways. Evident from the outset of the disease, the diversity of the luminal and basal pathways, together with cell lineage tracing studies, postulates the origin of molecularly distinct subtypes from different uroprogenitor cells. The molecular mechanisms initiating field effects involve a new class of genes referred to as forerunner (FR) genes that generally map around major tumor suppressors such as RB1. These genes are silenced, predominantly by hypermethylation and less frequently by mutations, and drive the expansion of intraurothelial preneoplastic cells. Different FR genes are involved in various molecular subtypes of bladder cancer and they sensitize the uroprogenitor cells to the development of luminal and basal bladder cancers in animal models. In human bladder cancer, luminal and basal forms have dissimilar clinical behavior and response to conventional and targeted chemotherapeutic manipulations. These new research developments hold the promise of expanding our armamentarium of diagnostic and treatment options for patients with bladder cancer and improving our ability to select patients most likely to respond to a specific therapy. PMID:26907529

  9. Chemoprevention of bladder cancer.

    Science.gov (United States)

    Kamat, Ashish M; Lamm, Donald L

    2002-02-01

    possibility with long-term administration, the dose should be decreased to 16,000 IU after 3 years. High doses of beta-carotene should be avoided based on a large clinical trial reporting a 25% increase in the number of cases of prostate cancer and a statistically significant increase in the incidence of lung cancer. Vitamin B6 has been studied in several clinical trials in bladder cancer. The US-based Veterans Administration cooperative study found benefit for vitamin B6 when given as a single agent. Data for vitamins C and E are insufficient to recommend either agent as stand-alone treatment. Nonetheless, each of these vitamins is known to have beneficial effects, including improved function of the immune system. It is possible that only a small percentage of patients with bladder cancer respond to vitamins B6, C, or E, yet each is safe, nontoxic, and inexpensive. In an effort to pool the efficacy of individual agents and to increase the power of study, the authors evaluated the combination of vitamins A, B6, C, and E in a double-blind trial. The observed 50% 5-year reduction in tumor recurrence was highly significant and greater than would be expected for any of the individual ingredients and suggests that combinations of nutritional agents may be most appropriate. A large-volume study along similar lines is being conducted. Among the numerous other compounds and dietary substances purported to have chemopreventive effect, soybeans, garlic, and green tea stand out as having the greatest promise and can freely be recommended to patients. For synthetically synthesized agents such as celecoxib, piroxicam, or DFMO, recommendations must be deferred until the results of clinical trials are conclusively in favor of their use. Many of the dietary factors found to be protective against bladder cancer are being investigated in other cancers and are beneficial to general health. Although naturally occurring nutrients are ideal, especially because the delicate balance of various

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Initial conservative treatment for grade 3 Ta-1 superficial bladder cancer

    International Nuclear Information System (INIS)

    We retrospectively investigated the therapeutic outcomes of our series of 7 Ta and 62 T1 bladder cancers with grade 3 (G3) malignancy in 61 men and 8 women having a mean age of 66.2 years. Following transurethral resection of bladder tumor (TURBT), 35 and 6 patients received intravesical instillations of bacillus Calmette-Guerin (BCG) and anthracycline-derivants, respectively, whereas 15 received no adjuvant therapy. Five and 2 patients received systemic and local chemotherapy with irradiation, respectively, and six underwent radical cystectomy for invasive potential. The 5-year non-recurrence, progression-free, and overall (cancer-specific) survival rates were 66, 82%, and 76 (88)%, respectively, after a median follow-up of 52 months. The 5-year non-recurrence rates were 24% in non-adjuvant, 85% in BCG, 0% in anthracycline-derivants, 65% in systemic and local chemoradiation therapy, and 68% in cystectomy. The 5-year progression-free and overall (cancer-specific) survival rates of the patients treated with BCG instillation were 91% and 94 (100)%. There were no significant differences in the 5-year non-recurrence and progression-free rates between 12 patients with carcinoma in situ (CIS) and 23 patients without CIS. Complete TUR of all visible tumors and a reliable histopathological diagnosis of appropriate specimens bearing the muscle layer are mandatory for assessment of recurrence. G3 Ta-1 bladder cancers and CIS showed a high risk of recurrence, and required aggressive treatment. Since BCG therapy following TURBT significantly reduced the risk of recurrence and progression, adjuvant BCG therapy is considered to be the most promising initial conservative treatment for G3 Ta-1 bladder cancers. (author)

  12. 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

  13. Treatment Options by Stage (Bladder Cancer)

    Science.gov (United States)

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

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

    OpenAIRE

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

    2012-01-01

    This study sought to evaluate the differential effects of bladder distention on point A-based (AICBT) and three-dimensional conformal intracavitary brachytherapy (3D-ICBT) planning for cervical cancer. Two sets of CT scans were obtained for ten patients to evaluate the effect of bladder distention. After the first CT scan, with an empty bladder, a second set of CT scans was obtained with the bladder filled. The clinical target volume (CTV), bladder, rectum, and small bowel were delineated on ...

  15. 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.

  16. Diet in bladder cancer ethiopathogenesis

    Directory of Open Access Journals (Sweden)

    Đokić M.

    2005-01-01

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

  17. 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; Thorsen, Kasper; Fristrup, Niels; Brems-Eskildsen, Anne Sofie; Madsen, Pia Pinholt; Sørensen, Karina Dalsgaard; Borre, Michael; Ørntoft, Torben Falck

    2013-01-01

    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......Background Human TOX3 (TOX high mobility group box family member 3) regulates Ca2+-dependent transcription in neurons and has been associated with breast cancer susceptibility. Aim of the study was to investigate the expression of TOX3 in bladder cancer tissue samples and to identify genes and...... identification and immunoprecipitation studies were used for DNA binding studies. Results Microarray transcript profiling of 89 bladder biopsies showed a significant upregulation of TOX3 (p< 10-4) in non-muscle invasive (Ta-T1) bladder tumors compared to muscle-invasive (T2-T4) bladder tumors and normal...

  18. Analysis of intravesical recurrence after bladder-preserving therapy for muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    The aim of the present study was to analyze the pattern of recurrences after bladder-preserving therapy for muscle-invasive bladder cancer. The subjects were 77 patients with T2-3N0M0 bladder cancer whose bladder was preserved by intra-arterial chemotherapy and radiation. The patterns of the first recurrences were retrospectively analyzed. With a median follow-up of 38.5 months, 17 patients (22.1%) experienced intravesical recurrence without metastasis, 14 (82.4%) of which were cases of non-muscle-invasive bladder cancer recurrence and 3 (17.6%) of which were muscle-invasive bladder cancer recurrences. Muscle-invasive bladder cancer recurred at the same site as the initial tumor site in all three cases, whereas non-muscle-invasive bladder cancer recurred at different sites in 64% of the patients in that group. The peak hazard of the non-muscle-invasive bladder cancer recurrence was observed at around a year after treatment. Recurrent non-muscle-invasive bladder cancer was of a significantly lower histological grade with lower Ki-67-labeling indices than the initial muscle-invasive bladder cancer. Twelve (85.7%) of 14 patients with non-muscle-invasive bladder cancer recurrence achieved disease-free status. The multivariate analysis revealed that multiplicity, grade and tumor size were significantly correlated with the recurrence (P=0.0001, 0.0442 and 0.0412, respectively). Most of the recurrences after bladder-preserving therapy were cases of non-muscle-invasive bladder cancer. The recurrence pattern and characteristics of the tumors did not differ from those of primary non-muscle-invasive bladder cancer. Patients with high-risk factors would be candidates for prophylactic intravesical therapy for non-muscle-invasive bladder cancer recurrence. (author)

  19. Contemporary Management of Bladder Cancer

    Science.gov (United States)

    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

  20. Bladder preservation using chemoradiation therapy for locally invasive bladder cancer

    International Nuclear Information System (INIS)

    We investigated the long-term results and molecular markers of outcome with selective organ preservation in invasive bladder cancer using chemoradiation therapy. We examined locally invasive bladder cancer in 32 patients (30 men, 2 women; mean age at treatment 68.1 years) who underwent bladder-sparing protocols in the Department of Urology at Sumitomo Hospital between 2000 and 2005. The clinical stage was T2, T3, and T4 in 13, 16, and 3 patients, respectively. Our protocol includes aggressive transurethral resection of the bladder tumor (TURBT) and 46 Gy radiotherapy (2 Gy/fraction, 5 fractions/week) to the pelvis with concurrent cisplatin chemotherapy (20 mg/body/day, 5 days/week, the first and fourth week, intravenously). The initial evaluation included magnetic resonance imaging (MRI), urine cytology, and cystoscopy with a biopsy. During follow-up, if the patients developed superficial recurrence, they was treated with TURBT and intravesical Bacillus Calmette-Guerin (BCG), while patients with invasive recurrence were advised to undergo a salvage cystectomy. We examined the association between the expression of the Bcl-2 family in pretreatment TUR specimens and patient outcome. The mean follow-up was 54.6 months. The first assessment after the induction chemoradiotherapy showed that bladder preservation was achieved in 27 patients (84.4%). The actuarial local control rate with an intact bladder was 56.3% (18 patients) at 3 years. The 1-, 3-, and 5-year cancer-specific survival rate was 90.6, 84.0, and 66.9%, respectively. The 5-year cancer-specific survival rate was 75.0, 67.2, and 33.3% in T2, T3, and T4, respectively. Bcl-x positivity was significantly associated with a poor cancer-specific survival rate (log-rank test, p=0.038). Chemoradiation therapy for invasive bladder cancer can achieve survival rates similar to those in patients treated with radical cystectomy, with successful bladder preservation. Our results suggest that the expression of Bcl-x is a

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Immunotherapy for bladder cancer.

    Science.gov (United States)

    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

  3. Immunotherapy for bladder cancer

    Directory of Open Access Journals (Sweden)

    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

  4. Drugs Approved for Bladder Cancer

    Science.gov (United States)

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

  5. 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 (p<10-4) in non-muscle invasive (Ta-T1) bladder tumors compared to muscle-invasive (T2-T4) bladder tumors and normal...... urothelium. Microarray expression profiling of human bladder cancer cells over expressing TOX3 followed by Pathway analysis showed that TOX3 Overexpression mainly affected the Interferon Signaling Pathway. TOX3 up regulation induced the expression of several genes with a gamma interferon activation site (GAS...... 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...

  6. 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.

  7. 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

  8. 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.

  9. 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

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

    Science.gov (United States)

    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

  11. Ct2 Bladder Cancer.

    Science.gov (United States)

    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

  12. Genetic variation in DROSHA 3'UTR regulated by hsa-miR-27b is associated with bladder cancer risk.

    Directory of Open Access Journals (Sweden)

    Lin Yuan

    Full Text Available PURPOSE: miRNAs can regulate the biological processes, including differentiation, proliferation and apoptosis. DICER and DROSHA are two members of RNase III family, playing pivotal roles in the pathway of miRNAs biogenesis. In this study, we hypothesized that genetic variations of the DICER and DROSHA genes were associated with the bladder cancer risk. EXPERIMENTAL DESIGN: We performed a case-control study of 685 bladder cancer cases and 730 controls to investigate the association between the seven functional SNPs of DICER and DROSHA genes and bladder cancer risk. We then evaluated the functionality of the important SNPs. RESULTS: We found that rs10719T>C polymorphism located in 3' untranslated region (UTR of DROSHA gene was associated with the increased risk of bladder cancer. Stratified analysis suggested that rs10719TC/CC genotype can increase risk of bladder cancer among male patients (Adjusted OR = 1.34, 95% CI = 1.05-1.70, P = 0.018, and ever smokers (1.56, 1.14-2.14, 0.006, compared with TT genotype. Furthermore, DROSHA rs10719T>C polymorphism was predicted to regulate the binding activity of hsa-miR-27a/b. Luciferase reported gene assay confirmed that rs10719 T to G substitution disrupted the binding site for hsa-miR-27b, resulting the increased levels of DROSHA protein. CONCLUSIONS: Taken together, these findings suggested that DROSHA rs10719T>C polymorphism may be associated with bladder cancer risk in a Chinese population, and hsa-miR-27b can influence the expression of DROSHA protein by binding with 3'UTR.

  13. 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. ...

  14. Urinary Bladder Cancer in Yemen

    OpenAIRE

    Abdullah Saleh Al-Samawi; Saleh Mansoor Aulaqi

    2013-01-01

    Objectives: The aims of this study are to highlight the clinicopathological features of urinary bladder cancer in Yemen, and to describe the histological grading of urothelial neoplasms according to the World Health Organization and International Society of Urologic pathology (WHO/ISUP 1998) classification.Methods: This is a descriptive record-based study of 316 cases of bladder cancer diagnosed by two pathologists at the Department of pathology, Sana'a University from 1st January 2005 to 30t...

  15. Diet in bladder cancer ethiopathogenesis

    OpenAIRE

    Đokić M.; Janković Slavenka M.; Ilić M.; Radosavljević V.

    2005-01-01

    The aim of this paper is to show influence of different foods on bladder cancer appearance, as well as possible consequent ways of prevention. Consumption of food rich in animal fat and cholesterol, fried foods, especially several times used cookin oil for frying, processed meat with additives (nitrates, nitrites, azo-colourrs) can influence bladder cancer occurrence. Regularly, continuous consumption of fermented milk products, which contains come types of milky - acids bacterias, is conside...

  16. Urinary Bladder Cancer in Yemen

    Directory of Open Access Journals (Sweden)

    Abdullah Saleh Al-Samawi

    2013-09-01

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

  17. 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

  18. Bladder cancer immunotherapy.

    Science.gov (United States)

    Lamm, D L; Thor, D E; Stogdill, V D; Radwin, H M

    1982-11-01

    A randomized controlled prospective evaluation of intravesical and percutaneous bacillus Calmette-Guerin immunotherapy was done in 57 patients with transitional cell carcinoma of the bladder. In addition, 9 patients at high risk for tumor recurrence were treated with bacillus Calmette-Guerin produced a self-limited cystitis and 1 complication (hydronephrosis) of immunotherapy was observed. Of the 57 randomized patients 54 were followed for 3 to 30 months. Tumor recurrence was documented in 13 of 26 controls (50 per cent) and only 6 of 28 patients (21 per cent) treated with bacillus Calmette-Guerin (p equals 0.027, chi-square). The interval free of disease was prolonged significantly with bacillus Calmette-Guerin treatment (p equals 0.014, generalized Wilcoxon test). Importantly, a simple purified protein derivative skin test distinguished those patients who responded to bacillus Calmette-Guerin immunotherapy from those who did not. Only 1 of 17 treated patients (6 per cent) whose purified protein derivative test converted from negative to positive had tumor recurrence compared to 5 recurrences (38 per cent) among the 13 patients whose test remained negative or had been positive before treatment (p equals 0.022, chi-square). Bacillus Calmette-Guerin was given to 10 patients with stage B transitional cell carcinoma who were not candidates for cystectomy and 7 are free of disease. Of 5 patients with carcinoma in situ 3 remain free of tumor after bacillus Calmette-Guerin treatment and 5 of 6 who had multiple recurrences after intravesical chemotherapy responded favorably to bacillus Calmette-Guerin immunotherapy. PMID:6757467

  19. 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.

  20. Immunotherapeutic strategies for bladder cancer.

    Science.gov (United States)

    Chevalier, Mathieu F; Nardelli-Haefliger, Denise; Domingos-Pereira, Sonia; Jichlinski, Patrice; Derré, Laurent

    2014-01-01

    Bladder cancer is a common urologic malignancy with rising incidence in the elderly population. In most cases, bladder cancer is non-muscle-invasive at diagnosis and shows dramatically high recurrence rates, although current treatments often reduce the risk of disease progression. Immunotherapy using intravesical instillation of Bacillus Calmette-Guérin (BCG) remains the most effective therapy for patients with high risk tumors. However, BCG-therapy has important limitations including substantial adverse events and frequent treatment failure. Thus, it appears crucial to either improve or replace current therapy using new immunotherapeutic strategies. Here, we discuss the clinical trials that assessed therapeutic vaccination of bladder cancer patients using tumor associated antigens and we also argue for novel approaches arising from murine models. Vaccination routes to induce appropriate T-cell homing in the tumor site as well as the use of local immunostimulation to enhance recruitment of vaccine-induced T cells are discussed to highlight what we believe is a promising therapeutic vaccination strategy for patients with non-muscle-invasive bladder cancer. PMID:24384699

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

    International Nuclear Information System (INIS)

    This study sought to evaluate the differential effects of bladder distention on point A-based (AICBT) and three-dimensional conformal intracavitary brachytherapy (3D-ICBT) planning for cervical cancer. Two sets of CT scans were obtained for ten patients to evaluate the effect of bladder distention. After the first CT scan, with an empty bladder, a second set of CT scans was obtained with the bladder filled. The clinical target volume (CTV), bladder, rectum, and small bowel were delineated on each image set. The AICBT and 3D-ICBT plans were generated, and we compared the different planning techniques with respect to the dose characteristics of CTV and organs at risk. As a result of bladder distention, the mean dose (D50) was decreased significantly and geometrical variations were observed in the bladder and small bowel, with acceptable minor changes in the CTV and rectum. The average D2cm3 and D1cm3 showed a significant change in the bladder and small bowel with AICBT; however, no change was detected with the 3D-ICBT planning. No significant dose change in the CTV or rectum was observed with either the AICBT or the 3D-ICBT plan. The effect of bladder distention on dosimetrical change in 3D-ICBT planning appears to be minimal, in comparison with AICBT planning. (author)

  2. 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

  3. A functional variant in TP63 at 3q28 associated with bladder cancer risk by creating an miR-140-5p binding site.

    Science.gov (United States)

    Wang, Meilin; Du, Mulong; Ma, Lan; Chu, Haiyan; Lv, Qiang; Ye, Dingwei; Guo, Jianming; Gu, Chengyuan; Xia, Guowei; Zhu, Yao; Ding, Qiang; Yuan, Lin; Fu, Guangbo; Tong, Na; Qin, Chao; Yin, Changjun; Xu, Jianfeng; Zhang, Zhengdong

    2016-07-01

    The first genome-wide association study (GWAS) for bladder cancer has identified a susceptibility locus at 3q28 in the European ancestry. However, the causal variant at 3q28 remains unknown. We conducted a three-stage fine mapping study to identify potential causal variants in the region. A total of 41 single nucleotide polymorphisms (SNPs) across 120 kb at 3q28 were tested for association with bladder cancer risk among 3,094 bladder cancer cases and 3,738 controls. Resequencing and functional assays were further evaluated. The SNP rs35592567 in the 3'-UTR of TP63 was consistently associated with bladder cancer risk in all three stages. In the combined analysis, the T allele of rs35592567 was significantly associated with a decreased risk for bladder cancer (OR = 0.82, 95% CI = 0.75-0.90, P = 9.797 × 10(-6) in the additive model). Biochemical assays revealed that the T allele reduced the post-transcriptional levels of TP63 mediated by interfering binding efficiency of miR-140-5p. In addition, overexpression of miR-140-5p inhibited bladder cancer cell proliferation and attenuated cell migration, invasion and G1 cell-cycle arrest. Together, these results suggest that rs35592567 in TP63 may be a novel causal variant contributing to the susceptibility to bladder cancer, which provides additional insight into the pathogenesis of bladder carcinogenesis. PMID:26695686

  4. 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 ...

  5. [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

  6. 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.

  7. Genetic instability in urinary bladder cancer: An evolving hallmark

    Directory of Open Access Journals (Sweden)

    N Wadhwa

    2013-01-01

    Full Text Available Bladder cancer is a major health-care concern. A successful treatment of bladder cancer depends on its early diagnosis at the initial stage. Genetic instability is an essential early step toward the development of bladder cancer. This instability is found more often at the chromosomal level than at the nucleotide level. Microsatellite and chromosomal instability markers can be used as a prognostic marker for screening bladder cancer. Bladder cancer can be distinguished in two different categories according to genetic instability: Cancers with chromosomal level instability and cancers with nucleotide level instability. Deoxyribonucleic acid (DNA mismatch repair (MMR system and its correlation with other biologic pathway, both are essential to understand the basic mechanisms of cancer development. Microsatellite instability occurs due to defects in DNA MMR genes, including human mutL homolog 1 and human mutL homolog 2. Chromosomal alterations including deletions on chromosome 3, 8, 9, 11, 13, 17 have been detected in bladder cancer. In the current review, the most recent literature of genetic instability in urinary bladder cancer has been summarized.

  8. 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.

  9. What Is Bladder Cancer?

    Science.gov (United States)

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

  10. Chemoimmunotherapy of murine bladder cancer.

    Science.gov (United States)

    Stogdill, B J; Lamm, D L; Livingston, R B

    1981-11-01

    The lethality of invasive transitional cell carcinoma (TCC) has prompted a search for effective, minimally toxic, adjuvant therapy. Such agents were evaluated in a murine bladder cancer (MBT2) model which parallels the clinical disease. One hundred C3H/He mice were inoculated i.d. with 2.5 x 10(4) viable MBT2 tumor cells and randomized to receive either normal saline (control), cis-Platinum (CPT), cyclophosphamide (CY), methotrexate (MTX), BCG, (CY + MTX), or (CY + MTX + BCG). Chemotherapy was given intraperitoneally weekly starting on day 7 after inoculation. Immunotherapy was given intralesionally on days 1 and 10 only. All mice were treated for 5 weeks followed by 5 weeks of observation. At 5 weeks, tumors of mice receiving cyclophosphamide alone or either of the combinations of therapy were smaller (P less than 0.01) than tumors of controls or other single agents alone. Each regimen increased survival, but only the combination regimen increase survival significantly (P less than 0.01). In the doses and schedule used in this model. Combination chemotherapy and chemoimmunotherapy significantly delay tumor growth and increase duration of survival (P less than 0.01) when compared with controls or single agent groups. PMID:7298287

  11. 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

  12. 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...

  13. 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

  14. 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...

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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

  20. Bladder and rectum dose define 3D treatment planning for cervix cancer brachytherapy comparison of dose volume histograms for organ contour and organ wall contour

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Won [Myongji Hospital, Gangneong (Korea, Republic of); Kim, Jong Won; Kim, Dae Hyun; Choi, Joon Yong [The Catholic Univ. of Korea College of Medicine, Seoul (Korea, Republic of); Choi, Joon Yong [Dongguk Univ. Medical Center, Seoul (Korea, Republic of); Won, Yeong Jin [Inje Univ. lsan Paik Hospital, Goyang (Korea, Republic of)

    2012-12-15

    To analyze the correlation between dose volume histograms(DVH) based on organ outer wall contour and organ wall delineation for bladder and rectum, and to compare the doses to these organs with the absorbed doses at the bladder and rectum. Individual CT based brachytherapy treatment planning was performed in 13 patients with cervical cancer as part of a prospective comparative trial. The external contours and the organ walls were delineated for the bladder and rectum in order to compute the corresponding dose volume histograms. The minimum dose in 0.1 cm{sup 3}, 1 cm{sup 3}, 2 cm{sup 3}, 5 cm{sup 3}, 10 cm{sup 3} volumes receiving the highest dose were compared with the absorbed dose at the rectum and bladder reference point. Results: The bladder and rectal doses derived from organ outer wall contour and computed for volumes of 2 cm{sup 3}, provided a good estimate for the doses computed for the organ wall contour only. This correspondence was no longer true when large volumes were considered. For clinical applications, when volumes smaller than 5 cm{sup 2} are considered, the dose.volume histograms computed from external organ contours for the bladder and rectum can be used instead of dose.volume histograms computed for the organ walls only. External organ contours are indeed easier to obtain. The dose at the ICRU rectum reference point provides a good estimate of the rectal dose computed for volumes smaller than 2 cm{sup 2} only for a midline position of the rectum. The ICRU bladder reference point provides a good estimate of the dose computed for the bladder wall only in cases of appropriate balloon position.

  1. 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)

  2. Tetrachloroethylene exposure and bladder cancer risk

    DEFF Research Database (Denmark)

    Vlaanderen, Jelle; Straif, Kurt; Ruder, Avima; Blair, Aaron; Hansen, Johnni; Lynge, Elsebeth; Charbotel, Barbara; Loomis, Dana; Kauppinen, Timo; Kyyronen, Pentti; Pukkala, Eero; Weiderpass, Elisabete; Guha, Neela

    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......-analysis demonstrates an increased risk of bladder cancer in dry cleaners, reported in both cohort and case-control studies, and some evidence for an exposure-response relationship. Although dry cleaners incur mixed exposures, tetrachloroethylene could be responsible for the excess risk of bladder cancer because it is...

  3. 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

  4. 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

  5. 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)

  6. 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.

  7. 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...

  8. 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...

  9. 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

  10. 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...

  11. 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

  12. Chemotherapy and Targeted Therapy for Gall Bladder Cancer

    OpenAIRE

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

    2014-01-01

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

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

    International Nuclear Information System (INIS)

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

  14. Hemipelvic irradiation for superficial bladder cancer

    International Nuclear Information System (INIS)

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

  15. 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...

  16. Histopathological characterization of a syngeneic orthotopic murine bladder cancer model

    Directory of Open Access Journals (Sweden)

    Daher C. Chade

    2008-03-01

    Full Text Available PURPOSE: We developed and characterized by histopathology and immunohistochemistry a syngeneic murine bladder tumor model derived from the MB49 tumor cell line. MATERIALS AND METHODS: Bladder tumor implantation was achieved by intravesical instillation of 5 x 10(5 MB49 tumor cells in C57BL/6 mice. A chemical lesion of the bladder was performed in order to promote intravesical tumor implantation. The bladder wall lesion was accomplished by transurethral instillation of silver nitrate (AgNO3. After 15 days, the animals were sacrificed, examined macroscopically for intravesical tumor and bladder weight. Histology and immunohistochemistry were performed using cytokeratin 7 (CK7, carcinoembrionic antigen (Dako-CEA, p53 and c-erbB2 oncoprotein (Her2/neu. RESULTS: Twenty-nine out of 30 animals (96.7% developed intravesical tumors in a 15-day period. Macroscopically, the mean bladder weight was 0.196g (0.069-0.538g, 10 to 15 times the normal bladder weight. The immunohistochemical analysis showed significant membrane expression of CEA and CK7: a similar finding for human urothelial cancer. We also characterized absence of expression of p53 and anti-Her2/neu in the murine model. CONCLUSIONS: High tumor take rates were achieved by using the chemical induction of the bladder tumor. Although electric cauterization is widely described in the literature for syngeneic orthotopic animal models, the technique described in this study represents an alternative for intravesical bladder tumor implantation. Moreover, the histopathology and immunohistochemical analysis of the murine bladder tumor model derived from the MB49 cell line showed a resemblance to human infiltrating urothelial carcinoma, allowing clinical inference from experimental immunotherapy testing.

  17. Concomitant boost radiotherapy for muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Purpose: To evaluate the feasibility and efficacy of a concomitant partial bladder boost schedule in radiotherapy for invasive bladder cancer, coupling a limited boost volume with shortening of the overall treatment time. Methods and materials: Between 1994 and 1999, 50 patients with a T2-T4 N0M0 transitional cell carcinoma of the bladder received radiotherapy delivered in a short overall treatment time with a concomitant boost technique. With this technique a dose of 40 Gy in 2-Gy fractions was administered to the small pelvis with a concomitant boost limited to the bladder tumor area plus margin of 15 Gy in fractions of 0.75 Gy. The total tumor dose was 55 Gy in 20 fractions in 4 weeks. Toxicity was scored according to EORTC/RTOG toxicity criteria. Results: The feasibility of the treatment was good. Severe acute toxicity ≥G3 was observed in seven patients (14%). Severe late toxicity ≥G3 was observed in six patients (13%). Thirty-seven patients (74%) showed a complete and five (10 %) a partial remission after treatment. The actuarial 3-year freedom of local progression was 55%. Conclusion: In external radiotherapy for muscle invasive bladder cancer a concomitant boost technique coupling a partial bladder boost with shortening of the overall treatment time provides a high probability of local control with acceptable toxicity

  18. 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

  19. 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...

  20. Factors influencing the prognosis in bladder cancer

    International Nuclear Information System (INIS)

    In the categories T1, T2 and T3NxM0 bladder cancer, with a diameter not exceeding 5 cm, the treatment in the Rotterdam Radio-Therapy Institute consists of interstitial irradiation with needles containing radioactive material. The results of treatment and the role of additional external irradiation are discussed. Category T3NxM0 tumors with a diameter exceeding 5 cm are treated by external irradiation followed by cystectomy; the results are presented here. Factors influencing prognosis appeared to be the degree of differentiation, number of transurethral resections (TURs) prior to definitive treatment, intravenous pyelography (IVP), vascular invasion, T category after preoperative irradiation, and postsurgical histopathologically-assessed T category (pT)

  1. 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

  2. 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

  3. Microsatellite instability in bladder cancer

    DEFF Research Database (Denmark)

    Gonzalez-Zulueta, M; Ruppert, J M; Tokino, K; Tsai, Y C; Spruck, C H; Miyao, N; Nichols, P W; Hermann, G G; Horn, T; Steven, 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 chr...

  4. 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...

  5. 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 ...

  6. 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, ...

  7. 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

  8. 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.

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

    OpenAIRE

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

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

  11. 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.

  12. A Methylation Panel for Bladder Cancer — EDRN Public Portal

    Science.gov (United States)

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

  13. Cancer of the Urinary Bladder

    Science.gov (United States)

    ... see tailored statistics, browse the SEER Cancer Statistics Review . To see statistics for a specific state, go to the State ... which can be found in the SEER Cancer Statistics Review . In some cases, different year spans may be ...

  14. 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 ...

  15. 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: A...

  16. Histologic variants of urothelial bladder cancer and nonurothelial histology in bladder cancer

    OpenAIRE

    Chalasani, Venu; Chin, Joseph L.; Izawa, Jonathan I.

    2009-01-01

    Bladder cancer can be classified histologically as urothelial or non-urothelial. Urothelial cancer has a propensity for divergent differentiation, which has increasingly been recognized in recent years due to heightened awareness and improved immunohistochemistry techniques. Furthermore, the recent World Health Organization classification of urothelial cancers improved clarity on this issue, with its listing of 13 histologic variants of urothelial cancer. The divergent differentiation pattern...

  17. 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.

  18. 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)

  19. 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.

  20. Paraneoplastic retinopathy associated with occult bladder cancer

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  1. 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

  2. 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...

  3. Metastatic Bladder Cancer: A Review of Current Management

    OpenAIRE

    Andrew Fletcher; Ananya Choudhury; Nooreen Alam

    2011-01-01

    Bladder cancer continues to result in substantial morbidity and mortality for affected individuals. Advances in the management of metastatic bladder cancer have been limited. Chemotherapy with platinum-based regimes remains the mainstay of first-line treatment. Studies investigating alternative regimes have offered no survival advantage. Targeted therapies may offer benefit either as single agent or in combination with chemotherapy. Symptoms due to metastatic bladder cancer impact patients' q...

  4. Selective cytotoxicity of squamocin on T24 bladder cancer cells at the S-phase via a Bax-, Bad-, and caspase-3-related pathways.

    Science.gov (United States)

    Yuan, Shyng-Shiou F; Chang, Hsueh-Ling; Chen, Hsiao-Wen; Kuo, Fu-Chen; Liaw, Chih-Chuang; Su, Jinu-Huang; Wu, Yang-Chang

    2006-01-18

    Annonaceous acetogenins are a group of potential anti-neoplastic agents isolated from Annonaceae plants. We purified squamocin, a cytotoxic bis-tetrahydrofuran acetogenin, from the seeds of Annona reticulata and analyzed its biologic effects on cancer cells. We showed that squamocin was cytotoxic to all the cancer lines tested. Furthermore, squamocin arrested T24 bladder cancer cells at the G1 phase and caused a selective cytotoxicity on S-phase-enriched T24 cells. It induced the expression of Bax and Bad pro-apoptotic genes, enhanced caspase-3 activity, cleaved the functional protein of PARP and caused cell apoptosis. These results suggest that squamocin is a potentially promising anticancer compound. PMID:16154156

  5. 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 ...

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

    Directory of Open Access Journals (Sweden)

    Dong-Suk Kim

    2002-02-01

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

  7. 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.

  8. 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 ...

  9. GATA3 in the urinary bladder: suppression of neoplastic transformation and down-regulation by androgens

    OpenAIRE

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

    2014-01-01

    Recent evidence suggests the involvement of sex hormone receptors in bladder cancer initiation, while precise functions of androgens and estrogens in the carcinogenesis step remain poorly understood. We recently found down-regulation of GATA3, a zinc-finger transcription factor and a new urothelial marker, in bladder cancer, which also correlated with expression status of androgen receptor (AR) and estrogen receptors (ERs). We here assessed whether GATA3 acted as a suppressor of bladder tumor...

  10. 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

  11. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Frolich, Camilla; Albrechtsen, Reidar; Andersen, Lars Dyrskjøt; Rudkjær, Lise; Ørntoft, Torben Falck; Wewer, Ulla M.

    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...... 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 in the...

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

    OpenAIRE

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

    2013-01-01

    Background Bladder calculus is associated with chronic irritation and inflammation. As there is substantial documentation that inflammation can play a direct role in carcinogenesis, to date the relationship between stone formation and bladder cancer (BC) remains unclear. This study aimed to examine the association between BC and prior bladder calculus using a population-based dataset. Methods This case–control study included 2,086 cases who had received their first-time diagnosis of BC betwee...

  13. 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.

  14. Testis expressed 19 is a novel cancer-testis antigen expressed in bladder cancer.

    Science.gov (United States)

    Zhong, Jianhua; Chen, Yan; Liao, Xinhui; Li, Jiaqiang; Wang, Han; Wu, Chenglong; Zou, Xiaowen; Yang, Gang; Shi, Jing; Luo, Liya; Liu, Litao; Deng, Jianping; Tang, Aifa

    2016-06-01

    Bladder cancer exhibits high mortality as a result of limited therapeutic options and a high recurrence rate. Accordingly, novel treatments such as immunotherapy have emerged as promising therapeutic modalities to prolong overall patient survival and effect a disease cure, which has renewed enthusiasm for the identification of tumor-specific target antigens. Cancer-testis (CT) antigens are recognized as ideal targets for immunotherapy because of their expression features and high immunogenicity profiles. Here, we investigate the expression pattern of a novel CT antigen, testis-expressed 19 (TEX19), in patients with bladder carcinoma and among multiple human tissues. Six bladder cancer cell lines (T24, UM-UC-3, J82, 5637, SW780, and RT4) were also analyzed for TEX19 expression. Our results reveal that TEX19 expression in normal tissue is restricted to human testis. In addition, TEX19 mRNA expression was detected in 60 % (24/40) bladder cancer samples, whereas 58.20 % (110/189) were positive for TEXT19 protein expression. Compared to low-grade tumors, TEX19 exhibited increased expression in high-grade tumors, from 53.69 to 77.14 %, respectively (P = 0.011). TEX19 was also expressed in all six bladder cancer cell lines. Together, our findings suggest that TEX19 represents a novel CT gene and might play a role in the progression of bladder cancer and that this gene therefore provides a potential target for immunotherapy treatment strategies against bladder cancer. PMID:26695143

  15. 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...

  16. 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

  17. A Case of Multiple Myeloma Following Bladder Cancer

    Science.gov (United States)

    Shafi, Hamid; Vakili Sadeghi, Mohsen; Ghorbani, Hosein; Sharbatdaran, Majid

    2016-01-01

    Second primary malignancy following multiple myeloma (MM) was reported several years ago. There are also rare reports of cases with synchronous MM and other malignancies. To our knowledge, only one case of MM following bladder cancer has been reported in the literature. Here, we report the second case occurred three months after diagnosis of bladder cancer.

  18. 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.

  19. 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

  20. The FUSE binding proteins FBP1 and FBP3 are potential c-myc regulators in renal, but not in prostate and bladder cancer

    International Nuclear Information System (INIS)

    The three far-upstream element (FUSE) binding proteins (FBP1, FBP2, and FBP3) belong to an ancient family of single-stranded DNA binding proteins which are required for proper regulation of the c-myc proto-oncogene. Whereas it is known that c-myc alterations play a completely different role in various carcinomas of the urogenital tract, the relevance of FBPs is unclear. FBP1, FBP3 and c-myc expression was studied in 105 renal cell, 95 prostate and 112 urinary bladder carcinomas by immunohistochemistry using tissue microarrays. High rates of FBP1 and FBP3 expression were observed in all cancer types. There was a concomitant up-regulation of FBP1 and FBP3 in renal cell and prostate carcinomas (p < 0.001 both). C-myc expression was detectable in 21% of prostate, 30% of renal and 34% of urothelial carcinomas. Interestingly, strong FBP1 and FBP3 expression was associated with c-myc up-regulation in clear cell renal cell carcinomas (p < 0.001 and 0.09 resp.), but not in bladder or prostate cancer. The correlation between FBP1/FBP3, c-myc and high proliferation rate in renal cell carcinoma provides strong in vivo support for the suggested role of FBP1 and FBP3 as activators of c-myc. The frequent up-regulation of FBP1 and FBP3 in urothelial and prostate carcinoma suggests that FBPs also have an important function in gene regulation of these tumors

  1. 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

  2. Outcome after BCG treatment for urinary bladder cancer may be influenced by polymorphisms in the NOS2 and NOS3 genes☆

    Science.gov (United States)

    Ryk, Charlotta; Koskela, Lotta Renström; Thiel, Tomas; Wiklund, N. Peter; Steineck, Gunnar; Schumacher, Martin C.; de Verdier, Petra J.

    2015-01-01

    Purpose Bacillus Calmette-Guérin (BCG)-treatment is an established treatment for bladder cancer, but its mechanisms of action are not fully understood. High-risk non-muscle invasive bladder-cancer (NMIBC)-patients failing to respond to BCG-treatment have worse prognosis than those undergoing immediate radical cystectomy and identification of patients at risk for BCG-failure is of high priority. Several studies indicate a role for nitric oxide (NO) in the cytotoxic effect that BCG exerts on bladder cancer cells. In this study we investigated whether NO-synthase (NOS)-gene polymorphisms, NOS2-promoter microsatellite (CCTTT)n, and the NOS3-polymorphisms-786T>C (rs2070744) and Glu298Asp (rs1799983), can serve as possible molecular markers for outcome after BCG-treatment for NMIBC. Materials and methods All NMIBC-patients from a well-characterized population based cohort were analyzed (n=88). Polymorphism data were combined with information from 15-years of clinical follow-up. The effect of BCG-treatment on cancer-specific death (CSD), recurrence and progression in patients with varying NOS-genotypes were studied using Cox proportional hazard-models and log rank tests. Results BCG-treatment resulted in significantly better survival in patients without (Log rank: p=0.006; HR: 0.12, p=0.048), but not in patients with a long version ((CCTTT)n ≧13 repeats) of the NOS2-promoter microsatellite. The NOS3-rs2070744(TT) and rs1799983(GG)-genotypes showed decreased risk for CSD (Log rank(TT): p=0.001; Log rank(GG): p=0.010, HR(GG): 0.16, p=0.030) and progression (Log rank(TT): p<0.001, HR(TT): 0.05, p=0.005; Log rank(GG): p<0.001, HR(GG): 0.10, p=0.003) after BCG-therapy compared to the other genotypes. There was also a reduction in recurrence in BCG-treated patients that was mostly genotype independent. Analysis of combined genotypes identified a subgroup of 30% of the BCG-treated patients that did not benefit from BCG-treatment. Conclusions Our results suggest that the

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

    Science.gov (United States)

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

    2016-02-01

    Patients with diabetes have a higher incidence of bladder cancer; however, the association between thiazolidinedione use and bladder cancer risk has been controversial. We aimed to investigate whether pioglitazone or rosiglitazone use is associated with bladder cancer risk in patients with type 2 diabetes mellitus.This nationwide nested case-control study used data set obtained from the Korean National Health Insurance Service National Sample Cohort 2002 to 2013. Among the 47,738 patients with incident diabetes, 85 cases of newly diagnosed bladder cancer and 850 controls (1:10 matched by age, sex, index year, and diabetes diagnosis year) were recruited. Type 2 diabetes mellitus and bladder cancer were diagnosed using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision code.More cases of bladder cancer were diagnosed in men (81.2%), and the stratified age peaked at 70 to 79 years old. Exclusive rosiglitazone use raised the incidence of bladder cancer (odds ratio [OR] = 3.07, 95% confidence interval [CI ] = 1.48-6.37). The risk of bladder cancer started to increase after less than 3 months use (OR = 3.30, 95% CI = 1.02-10.70) and peaked at 3 to 12 months of rosiglitazone use (OR = 4.48, 95% CI = 1.51-13.31). Patients were first exposed to exclusive rosiglitazone within 1 year (OR = 11.74, 95% CI = 2.46-56.12) and those who had consistently used it for 1 year (OR = 4.48 95% CI = 1.51-13.31), had higher risks of bladder cancer compared with nonthiazolidinedione users. Neither pioglitazone use nor exclusive pioglitazone use were associated with an increased incidence of bladder cancer.Rosiglitazone use is associated with an increased risk of incident bladder cancer independent of age and sex in patients with type 2 diabetes mellitus. The highest odds of bladder cancer in rosiglitazone users was seen in those with <1 year of exposure. PMID:26871835

  4. Proepithelin is an autocrine growth factor for bladder cancer

    OpenAIRE

    Lovat, Francesca; Bitto, Alessandro; Xu, Shi-Qiong; Fassan, Matteo; Goldoni, Silvia; Metalli, David; Wubah, Vera; McCue, Peter; Serrero, Ginette; Gomella, Leonard G.; Baffa, Raffaele; Iozzo, Renato V.; Morrione, Andrea

    2009-01-01

    The growth factor proepithelin functions as an important regulator of proliferation and motility. Proepithelin is overexpressed in a great variety of cancer cell lines and clinical specimens of breast, ovarian and renal cancer, as well as glioblastomas. Using recombinant proepithelin on 5637 transitional cell carcinoma-derived cells, we have shown previously that proepithelin plays a critical role in bladder cancer by promoting motility of bladder cancer cells. In this study, we used the ONCO...

  5. 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...... 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......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...

  6. Does phosphorylation of cofilin affect the progression of human bladder cancer?

    Directory of Open Access Journals (Sweden)

    Chung Hong

    2013-02-01

    Full Text Available Abstract Background We determined the differently expressed protein profiles and their functions in bladder cancer tissues with the aim of identifying possible target proteins and underlying molecular mechanisms for taking part in their progression. Methods We examined the expression of proteins by proteomic analysis and western blot in normal urothelium, non-muscle-invasive bladder cancers (NMIBCs, and muscle-invasive bladder cancers (MIBCs. The function of cofilin was analyzed using T24 human bladder cancer cells. Results The expression levels of 12 proteins were altered between bladder cancers and normal bladder tissues. Of these proteins, 14-3-3σ was upregulated in both NMIBCs and MIBCs compared with controls. On the other hand, myosin regulatory light chain 2, galectin-1, lipid-binding AI, annexin V, transthyretin, CARD-inhibitor of NF-κB-activating ligand, and actin prepeptide were downregulated in cancer samples. Cofilin, an actin-depolymerizing factor, was prominent in both NMIBCs and MIBCs compared with normal bladder tissues. Furthermore, we confirmed that cofilin phosphorylation was more prominent in MIBCs than in NMIBCs using immunoblotting and immunohistochemcal analyses. Epidermal growth factor (EGF increased the phosphorylation of cofilin and elevated the migration in T24 cells. Knockdown of cofilin expression with small interfering RNA attenuated the T24 cell migration in response to EGF. Conclusions These results demonstrate that the increased expression and phosphorylation of cofilin might play a role in the occurrence and invasiveness of bladder cancer. We suspected that changes in cofilin expression may participate in the progression of the bladder cancer.

  7. 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.

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

    International Nuclear Information System (INIS)

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

  9. 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.

  10. 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

  11. Novel variants in MLL confer to bladder cancer recurrence identified by whole-exome sequencing

    Science.gov (United States)

    Wang, Yongqiang; Huang, Yi; Liu, Huan; Li, Feida; He, Luyun; Sun, Da; Yu, Yuan; Li, Qiaoling; Huang, Peide; Zhang, Meng; Zhao, Xin; Bi, Tengteng; Zhuang, Xuehan; Zhang, Liyan; Lu, Jingxiao; Sun, Xiaojuan; Zhou, Fangjian; Liu, Chunxiao; Yang, Guosheng; Hou, Yong; Fan, Zusen; Cai, Zhiming

    2016-01-01

    Bladder cancer (BC) is distinguished by high rate of recurrence after surgery, but the underlying mechanisms remain poorly understood. Here we performed the whole-exome sequencing of 37 BC individuals including 20 primary and 17 recurrent samples in which the primary and recurrent samples were not from the same patient. We uncovered that MLL, EP400, PRDM2, ANK3 and CHD5 exclusively altered in recurrent BCs. Specifically, the recurrent BCs and bladder cancer cells with MLL mutation displayed increased histone H3 tri-methyl K4 (H3K4me3) modification in tissue and cell levels and showed enhanced expression of GATA4 and ETS1 downstream. What's more, MLL mutated bladder cancer cells obtained with CRISPR/Cas9 showed increased ability of drug-resistance to epirubicin (a chemotherapy drug for bladder cancer) than wild type cells. Additionally, the BC patients with high expression of GATA4 and ETS1 significantly displayed shorter lifespan than patients with low expression. Our study provided an overview of the genetic basis of recrudescent bladder cancer and discovered that genetic alterations of MLL were involved in BC relapse. The increased modification of H3K4me3 and expression of GATA4 and ETS1 would be the promising targets for the diagnosis and therapy of relapsed bladder cancer. PMID:26625313

  12. 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.

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

    International Nuclear Information System (INIS)

    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

  14. 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.

  15. Diabetes Pharmacotherapies and Bladder Cancer: A Medicare Epidemiologic Study

    OpenAIRE

    MacKenzie, Todd A.; Zaha, Rebecca; Smith, Jeremy; Karagas, Margaret R.; Morden, Nancy E.

    2016-01-01

    Objective Patients with type II diabetes have an increased risk of bladder cancer and are commonly treated with thiazolidinediones and angiotensin receptor blockers (ARBs), which have been linked to cancer risk. We explored the relationship between use of one or both of these medication types and incident bladder cancer among diabetic patients (diabetics) enrolled in Medicare. Research Design and Methods We constructed both a prevalent and incident retrospective cohort of pharmacologically tr...

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

    Science.gov (United States)

    Giedl, Johannes; Rogler, Anja; Wild, Andreas; Riener, Marc-Oliver; Filbeck, Thomas; Burger, Maximilian; Rümmele, Petra; Hurst, Carolyn; Knowles, Margaret; Hartmann, Arndt; Zinnall, Ulrike; Stoehr, Robert

    2016-01-01

    Activating mutations in the core promoter of the TERT gene have been described in many different tumor entities. In vitro models showed a two- to fourfold increase in transcriptional activity of the TERT promoter through creation of a consensus binding motif for Ets/TCF transcription factors caused by these mutations. TERT core promoter mutations are the most common mutations in bladder cancer with a frequency between 55.6% and 82.8% described so far, and are independent of stage and grade. Since limited data on molecular alterations of early-onset bladder tumors exists, we assessed the frequency of TERT core promoter mutations in early-onset bladder cancer. Two cohorts of bladder tumors (early-onset patient group; n=144 (age of onset of disease ≤45 years); unselected, consecutive group; n=125) were examined for TERT core promoter mutations. After microdissection and extraction of DNA the corresponding hotspot regions in the TERT core promoter were examined by Sanger-sequencing or a SNaPshot approach. A significantly lower frequency of TERT core promoter mutations was found in tumors from the early-onset cohort compared to the consecutive cohort (57.6% vs. 84.8%, p<0.001). Among the early-onset cohort cases younger than the cohort's median age of 39 years at disease onset showed a significantly reduced number of TERT promoter mutations (31/67, 46,3%) than cases aged between 39 and 45 years (52/77, 67.5%; p=0.012). This association was not found in the consecutive cases. Mutation status was independent of tumor stage and grade. We conclude that in tumors from early-onset bladder cancer patients TERT core promoter mutations are not as frequent as in bladder tumors from consecutive cases, but seem to play an important role there as well. In patients below 39 years of age TERT core promoter mutations are a more infrequent event, suggesting different mechanisms of tumorigenesis in these young patients. PMID:27313781

  17. 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...... conv-PTV. In conclusion, the results of this pilot study indicate that the use of a-PTVs could result in substantial decrease in the course averaged planning target volume. This reduction in the PTV is likely to decrease the radiation related toxicity and benefit bladder cancer patients. Currently...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-28

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

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

    International Nuclear Information System (INIS)

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

  1. 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)

  2. 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)

  3. 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.

  4. Immune checkpoint blockade therapy for bladder cancer treatment.

    Science.gov (United States)

    Kim, Jayoung

    2016-06-01

    Bladder cancer remains the most immunogenic and expensive malignant tumor in the United States today. As the 4th leading cause of death from cancer in United States, Immunotherapy blocking immune checkpoints have been recently been applied to many aggressive cancers and changed interventions of urological cancers including advanced bladder cancer. The applied inhibition of PD-1-PD-L1 interactions can restore antitumor T-cell activity and enhance the cellular immune attack on antigens. The overall goals of this short review article are to introduce current cancer immunotherapy and immune checkpoint inhibitors, and to provide new insight into the underlying mechanisms that block immune checkpoints in tumor microenvironment. Furthermore, this review will address the preclinical and clinical trials to determine whether bladder cancer patients could benefit from this new cancer therapy in near future. PMID:27326412

  5. 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.

  6. Selective bladder preservation by combined modality therapy for invasive bladder cancer

    International Nuclear Information System (INIS)

    Purpose/Objective: To assess the success of selective organ preservation or radical cystectomy in a large group of patients with muscle-invasive bladder cancer treated with induction by combined transurethral resection (TURBT), systemic chemotherapy and radiation therapy. Materials and Methods: 106 patients (median age 68 years) were treated with induction by maximal TURBT and 2 cycles of chemotherapy (methotrexate, cisplatin, vinblastine - MCV) followed by 39.6 Gy irradiation in 1.8 Gy fractions with concomitant cisplatin. Tumor response was then evaluated by cystoscopy, rebiopsy, and urine cytology. Complete responders were consolidated with radiation to 64.8 Gy and further cisplatin. Any subsequent isolated invasive local relapse was managed by cystectomy. Patients with any less than a complete response (CR) were recommended cystectomy. Median follow-up was 4.4 years. Kaplan-Meier analysis was used to assess outcome. Results: 74 CR patients (70%) and 7 non-cystectomy candidates with less than a CR (7%) received consolidation chemotherapy and radiation. 13 incomplete responders (12%) underwent immediate cystectomy. 6 patients underwent cystectomy because they could not tolerate induction chemo-radiation. 1 complete response patient underwent radical cystectomy. 83 patients completed their planned therapy but 5 died of treatment related toxicity during induction chemotherapy. Five year actuarial overall survival and disease-specific survival were 52% and 60% respectively. For T2 patients, actuarial overall survival was 63%, and for T3-4, 45%. Five year survival with an intact functioning bladder was 43%. Five year freedom from distant metastases was 66%. Of those who had a CR after TURBT and MCV, the risk of a subsequent invasive bladder relapse was 18% at 5 years. Of those who had a CR after the completion of induction chemotherapy and 39.6 Gy, this risk was 21%. 18 patients (17%) have experienced a non-invasive bladder relapse requiring further TUR and

  7. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-02-01

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

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

    International Nuclear Information System (INIS)

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

  10. The FUSE binding proteins FBP1 and FBP3 are potential c-myc regulators in renal, but not in prostate and bladder cancer

    Directory of Open Access Journals (Sweden)

    Meyer Hellmuth-Alexander

    2008-12-01

    Full Text Available Abstract Background The three far-upstream element (FUSE binding proteins (FBP1, FBP2, and FBP3 belong to an ancient family of single-stranded DNA binding proteins which are required for proper regulation of the c-myc proto-oncogene. Whereas it is known that c-myc alterations play a completely different role in various carcinomas of the urogenital tract, the relevance of FBPs is unclear. Methods FBP1, FBP3 and c-myc expression was studied in 105 renal cell, 95 prostate and 112 urinary bladder carcinomas by immunohistochemistry using tissue microarrays. Results High rates of FBP1 and FBP3 expression were observed in all cancer types. There was a concomitant up-regulation of FBP1 and FBP3 in renal cell and prostate carcinomas (p C-myc expression was detectable in 21% of prostate, 30% of renal and 34% of urothelial carcinomas. Interestingly, strong FBP1 and FBP3 expression was associated with c-myc up-regulation in clear cell renal cell carcinomas (p Conclusion The correlation between FBP1/FBP3, c-myc and high proliferation rate in renal cell carcinoma provides strong in vivo support for the suggested role of FBP1 and FBP3 as activators of c-myc. The frequent up-regulation of FBP1 and FBP3 in urothelial and prostate carcinoma suggests that FBPs also have an important function in gene regulation of these tumors.

  11. 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 ...

  12. 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...

  13. 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.

  14. Hedgehog Signaling Regulates Bladder Cancer Growth And Tumorigenicity

    OpenAIRE

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

    2012-01-01

    The role of HEDGEHOG (HH) signaling in bladder cancer remains controversial. The gene encoding the HH receptor and negative regulator PATCHED1 (PTCH1) resides on a region of chromosome 9q, one copy of which is frequently lost in bladder cancer. Inconsistent with PTCH1 functioning as a classic tumor suppressor gene, loss-of-function mutations in the remaining copy of PTCH1 are not commonly found. Here, we provide direct evidence for a critical role of HH signaling in bladder carcinogenesis. We...

  15. 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.

  16. 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

  17. 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.

  18. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-04-01

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

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

    International Nuclear Information System (INIS)

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

  1. 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

  2. Clinical results of a concomitant boost radiotherapy technique for muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Purpose: to update the results of external radiotherapy with a focal concomitant boost technique on local control and bladder function in patients with muscle-invasive bladder cancer. Patients and methods: the authors retrospectively evaluated 92 elderly or disabled patients with localized T2-4 N0-1 M0 transitional cell carcinoma of the bladder and a median age of 79 years, not suitable for radical surgery and treated between 1994 and 2005. Treatment consisted of a dose of 40 Gy/2 Gy to the small pelvis with a daily concomitant boost of 0.75 Gy to the tumor. Total dose was 55 Gy in 4 weeks. Results: complete remission rate after evaluation by means of cystoscopy at 3 months was 78%. 3-year local control rate amounted to 56%, and 3-year overall survival to 36%. The posttreatment bladder capacity was comparable with the pretreatment capacity and was ≥ 200 ml in 81% of the cases. Mean bladder capacity did not deteriorate at longer follow-up. Conclusion: the local control rate after external beam radiotherapy in elderly patients with a focal concomitant boost for localized muscle-invasive bladder cancer was 56% at 3 years. Functional bladder outcome was good. (orig.)

  3. Clinical results of a concomitant boost radiotherapy technique for muscle-invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Piet, A.H.M.; Hulshof, M.C.C.M.; Pieters, B.R.; Koning, C.C.E. [Dept. of Radiation Oncology, Academic Medical Center, Univ. of Amsterdam (Netherlands); Pos, F.J. [Dept. of Radiation Oncology, The Netherlands Cancer Inst., Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Reijke, T.M. de [Dept. of Urology, Academic Medical Center, Univ. of Amsterdam (Netherlands)

    2008-06-15

    Purpose: to update the results of external radiotherapy with a focal concomitant boost technique on local control and bladder function in patients with muscle-invasive bladder cancer. Patients and methods: the authors retrospectively evaluated 92 elderly or disabled patients with localized T2-4 N0-1 M0 transitional cell carcinoma of the bladder and a median age of 79 years, not suitable for radical surgery and treated between 1994 and 2005. Treatment consisted of a dose of 40 Gy/2 Gy to the small pelvis with a daily concomitant boost of 0.75 Gy to the tumor. Total dose was 55 Gy in 4 weeks. Results: complete remission rate after evaluation by means of cystoscopy at 3 months was 78%. 3-year local control rate amounted to 56%, and 3-year overall survival to 36%. The posttreatment bladder capacity was comparable with the pretreatment capacity and was {>=} 200 ml in 81% of the cases. Mean bladder capacity did not deteriorate at longer follow-up. Conclusion: the local control rate after external beam radiotherapy in elderly patients with a focal concomitant boost for localized muscle-invasive bladder cancer was 56% at 3 years. Functional bladder outcome was good. (orig.)

  4. 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

  5. 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

  6. 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

  7. Partially wedged beams improve radiotherapy treatment of urinary bladder cancer

    International Nuclear Information System (INIS)

    Background and purpose: Partially wedged beams (PWBs) having wedge in one part of the field only, can be shaped using dynamic jaw intensity modulation. The possible clinical benefit of PWBs was tested in treatment plans for muscle-infiltrating bladder cancer. Material and methods: Three-dimensional treatment plans for 25 bladder cancer patients were analyzed. The originally prescribed standard conformal four-field box technique, which includes the use of lateral ordinary wedge beams, was compared to a modified conformal treatment using customized lateral PWBs. In these modified treatment plans, only the anterior parts of the two lateral beams had a wedge. To analyze the potential clinical benefit of treatment with PWBs, treatment plans were scored and compared using both physical parameters and biological dose response models. One tumour control probability model and two normal tissue complication probability (NTCP) models were applied. Different parameters for normal tissue radiation tolerance presented in the literature were used. Results: By PWBs the dose homogeneity throughout the target volume was improved for all patients, reducing the average relative standard deviation of the target dose distribution from 2.3 to 1.8%. A consistent reduction in the maximum doses to surrounding normal tissue volumes was also found. The most notable improvement was demonstrated in the rectum where the volume receiving more than the prescribed tumour dose was halved. Treatment with PWBs would permit a target dose escalation of 2-6 Gy in several of the patients analyzed, without increasing the overall risk for complications. The number of patients suitable for dose escalation ranged from 3 to 15, depending on whether support from all or only one of the five applied NTCP model/parameter combinations were required in each case to recommend dose escalation. Conclusion: PWBs represent a simple dose conformation tool that may allow radiation dose escalation in the treatment of muscle

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

    International Nuclear Information System (INIS)

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

  9. 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...... interaction between smoking and N-acetyltransferase 2 slow acetylation (OR, 1.3; 95% confidence interval, 1.0-1.6) that was somewhat stronger when analyses were restricted to studies conducted in Europe (OR, 1.5; confidence interval, 1.1-1.9), a pooling that included nearly 80% of the collected data. Using...

  10. 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)

  11. 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)

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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...

  18. Research on the bioactivity of isoquercetin extracted from marestail on bladder cancer EJ cell and the mechanism of its occurrence.

    Science.gov (United States)

    Ran, Juhong; Wang, Yanping; Zhang, Wei; Ma, Minyu; Zhang, Haiying

    2016-05-01

    Research studies in recent years have found that isoquercetin has an inhibiting effect on multiple carcinogens, but research studies filed on isoquercetin in bladder cancer are quite few. This paper observed the influence of isoquercetin on biological activity of the EJ cell of bladder cancer through HC dyeing and trypan blue counting, studied the EJ cell cycle by flow cytometry (FCM), and then analyzed the influence of isoquercetin and its effect on the protein expression of STAT3 and STAT3-inhibiting factors (PIAS3) in EJ cells. Research has shown that isoquercetin has an inhibitory effect on the EJ cells of bladder cancer, but it is not obvious. PMID:25650648

  19. 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.

  20. 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

  1. Ruguo key genes and tumor driving factors identification of bladder cancer based on the RNA-seq profile

    Directory of Open Access Journals (Sweden)

    Zhang M

    2016-05-01

    Full Text Available Minglei Zhang,1 Hongyan Li,2 Di Zou,3 Ji Gao2 1Department of Orthopedics, Division of Tumor and Trauma Surgery, 2Department of Urology, China–Japan Union Hospital of Jilin University, 3Department of Nephrology, The First Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, People’s Republic of China Aim: This study aimed to select several signature genes associated with bladder cancer, thus to investigate the possible mechanism in bladder cancer.Methods: The mRNA expression profile data of GSE31614, including ten bladder tissues and ten control samples, was downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs in bladder cancer samples compared with the control samples were screened using the Student’s t-test method. Functional analysis for the DEGs was analyzed using the Database for Annotation, Visualization, and Integrated Discovery from the Gene Ontology database, followed by the transcription function annotation of DEGs from Tumor-Associated Gene database. Motifs of genes that had transcription functions in promoter region were analyzed using the Seqpos.Results: A total of 1,571 upregulated and 1,507 downregulated DEGs in the bladder cancer samples were screened. ELF3 and MYBL2 involved in cell cycle and DNA replication were tumor suppressors. MEG3, APEX1, and EZH2 were related with the cell epigenetic regulation in bladder cancer. Moreover, HOXB9 and EN1 that have their own motif were the transcription factors.Conclusion: Our study has identified several key genes involved in bladder cancer. ELF3 and MYBL2 are tumor suppressers, HOXB9 and EN1 are the main regulators, while MEG3, APEX1, and EZH2 are driving factors for bladder cancer progression. Keywords: bladder cancer, differentially expressed genes, tumor driving factor, function analysis

  2. 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...

  3. 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

  4. 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

  5. Redirecting neutrophils against bladder cancer cells by BCG and Smac mimetic combination

    OpenAIRE

    Jinesh G, Goodwin; Kamat, Ashish M

    2012-01-01

    Intravesical bacillus Calmette-Guérin (BCG) immunotherapy results in neutrophil recruitment and subsequent secretion of cytokines to eliminate non-muscle invasive bladder cancer cells. However, bladder cancer cells often resist BCG immunotherapy. Thus, understanding the mechanism of action of BCG, and designing appropriate combination therapies might help to overcome BCG resistance and redirect neutrophils against bladder cancer cells.

  6. 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 rat with seven fiberoptic temperature probes (OpSens Technologies, Quebec Canada) to characterize our ability to localize heat within the bladder target. Results The MRI study confirms the effectiveness of the catheterization procedure to homogenously distribute nanoparticles throughout the bladder. Thermal dosimetry data demonstrate our ability to controllably raise temperature of rat bladder >1°C/min to a steady-state of 42°C. Conclusion Our data demonstrate that a MFH system provides well-localized heating of rat bladder with effective control of temperature in the bladder and minimal heating of surrounding tissues.

  7. Individualized management of advanced bladder cancer: Where do we stand?

    Science.gov (United States)

    Burgess, Earle F

    2015-04-01

    Despite recent progress in the development of novel targeted therapies in various malignancies, the management of advanced urothelial cancer has changed little over the past 2 decades. Comorbidities inherent to patients with bladder cancer often preclude the use of standard cisplatin-based chemotherapy and underscore the need for individualized treatment recommendations and the development of more effective therapies. This review discusses current issues relevant to the management of patients with locally advanced and metastatic urothelial carcinoma of the bladder and highlights recent advances in defining molecular aberrations that may ultimately lead to personalized therapeutic decision making. PMID:24332641

  8. 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.

  9. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

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

    2006-01-01

    gene expression was evaluated in tumors from 96 patients with bladder cancer using a customized Affymetrix GeneChip. Gene expression in bladder cancer was validated using reverse transcription-PCR, quantitative PCR, and in situ hybridization. Protein expression was evaluated by immunohistochemical...... 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...

  10. 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

  11. 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 !

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

    Science.gov (United States)

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

    2016-01-01

    BACKGROUND Small cell carcinoma of the urinary bladder is a rare and aggressive form of bladder cancer that mainly presents at an advanced stage. As a result of its rarity, it has been described in many case reports and reviews but few retrospective and prospective trials, showing there is no standard therapeutic approach. In the literature the best therapeutic strategy for limited disease is the multimodality treatment and most authors have extrapolated treatment algorithms from the therapy recommendations of small cell lung cancer. CASE REPORT A 71-year-old male patient was referred to our hospital with gross hematuria and dysuria. Imaging and cystoscopy revealed a vegetative lesion of the bladder wall. A transurethral resection of the bladder was performed. Pathological examination revealed a pT2 high-grade urothelial carcinoma with widespread neuroendocrine differentiation. Multimodal treatment with neoadjuvant platinum-based chemotherapy was performed. A CT scan performed after chemotherapy demonstrated a radiological complete response. The patient underwent radical cystectomy and lymphadenectomy. The histopathological finding of bladder and node specimen confirmed a pathological complete response. A post-surgery CT scan showed no evidence of local or systemic disease. Six months after surgery, the patient is still alive and disease-free. CONCLUSIONS A standard treatment strategy of small cell cancer of the urinary bladder is not yet well established, but a multimodal treatment of this disease is the best option compared to surgical therapy alone. The authors confirm the use of neoadjuvant chemotherapy in limited disease of small cell carcinoma of the urinary bladder. PMID:27072610

  13. Bacillus Calmette-Guerin immunotherapy of superficial bladder cancer.

    Science.gov (United States)

    Lamm, D L; Thor, D E; Harris, S C; Reyna, J A; Stogdill, V D; Radwin, H M

    1980-07-01

    Thirty-seven patients were enrolled in a randomized prospective study to compare standard surgical therapy for superficial bladder cancer to standard therapy plus bacillus Calmette-Guerin (BCG). Side effects of BCG have been tolerated well and include dysuria in 95 per cent of the patients, urinary frequency in 83 per cent, hematuria in 39 per cent, fever in 22 per cent and nausea in 22 per cent. Of 19 control patients 8 (42 per cent) had recurrent tumors in the followup period, compared to 3 of 18 patients (17 per cent) treated with BCG. One patient treated wih BCG had 2 recurrences, yielding a recurrence rate of 22 per cent in the group receiving BCG compared to 42 per cent in controls. When the incidence of recurrent tumors in matched intervals before and after entry into the protocol is compared, no change in the rate of tumor recurrence (p equals 0.726 chi-square) occurred in controls, whereas tumor recurrences were reduced significantly in the group treated with BCG (p equals 0.010 chi-square). The reduction in tumor recurrence in patients treated with BCG compared to controls is statistically significant (p equals 0.029 chi-square). Of 4 patients who presented with new bladder tumors remain free of tumor after BCG therapy, while 2 of 5 comparable control patients developed recurrent tumors. Intravesical and percutaneous BCG immunotherapy appears to decrease the rate of tumor recurrence in patients followed for 1 year. PMID:6997513

  14. 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...

  15. Bladder and rectal complications following radiotherapy for cervix cancer

    International Nuclear Information System (INIS)

    One-hundred and thirty-two patients with cervix carcinoma who were treated with whole pelvis irradiation and two intracavitary applications had bladder and rectal dosimetry during brachytherapy with contrast agents placed into the bladder and rectum prior to orthogonal simulator radiographs. Doses were computer calculated at points A and B, F (bladder), R1 (rectum), and R2 (rectosigmoid). Late occurring bladder and rectal complications were graded on a severity scale of 1 to 3, and 14% had grade 2 or 3 injuries (9% developed fistulas). Statistical evaluation of the data showed that severe bladder and rectal injuries occur more commonly in stage IIIA and IIIB disease and in those receiving high external beam doses (5000 rad +). Analysis of variance tests revealed a significant correlation of brachytherapy dose to points R1 and R2 with severe rectal injuries but there was not a correlation of dose to F with bladder injuries. Nor was there correlation of injuries with dose to point A or the milligram-hour dose. We conclude that our technique for rectal dosimetry is adequate but that an improved technique of bladder dosimetry is needed. Also, when combining whole pelvis irradiation with two intracavitary applications (4000 rad to point A), the whole pelvis dose should probably not exceed 4000-4500 rad

  16. 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

  17. 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

  18. Radical radiotherapy for urinary bladder cancer: treatment outcomes

    DEFF Research Database (Denmark)

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

    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...

  19. 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.

  20. 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...

  1. Gene profiling suggests a common evolution of bladder cancer subtypes

    OpenAIRE

    Hansel, Donna E.; Zhang, ZhongFa; Petillo, David; Teh, Bin T.

    2013-01-01

    Abstract Background Bladder cancer exists as several distinct subtypes, including urothelial carcinoma (UCa), squamous cell carcinoma (SCCa), adenocarcinoma and small cell carcinoma. These entities, despite showing distinct morphology and clinical behavior, arise from the urothelial lining and are often accompanied by similar precursor/in situ findings. The relationship between these subtypes has not been explored in detail. ...

  2. 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

  3. 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...

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

    Directory of Open Access Journals (Sweden)

    K. M. Figurin

    2014-07-01

    Full Text Available 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.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Hexaminolevulinate (HAL) is an optical imaging agent used with fluorescence cystoscopy (FC) for the detection of non-muscle-invasive bladder cancer (NMIBC). Guidelines from the European Association of Urology (EAU) and a recent, more detailed European expert consensus statement agree that HAL...

  6. A review of molecular biomarkers for bladder cancer

    Directory of Open Access Journals (Sweden)

    Miakhil I

    2013-01-01

    Full Text Available Background: Numerous molecular markers for bladder cancer have been identified and investigated with various laboratory techniques. Molecular markers are isolated from tissue, serum and urine. They fall into proteomic, genetic and epigenetic categories. Some of molecular markers show promising results in terms of facilitating early diagnosis and guiding treatment. Molecular markers or the so- called biomarkers can provide additional information alongside staging, grading and lymphovascular invasion, for better prognostication.Aim:This studyprovides an up-to-date review of the frequently studied and most important biomarkers that have shown consistent relevance in relation to bladder cancer. Methods: The key words were searched on the PubMed, Google scholar and NHS library search engines. Results: More than twenty biomarkers as per our methodology were identified but only half of them have shown consistence relevance in bladder cancer. Conclusion: It is envisaged that a combination of a few biomarkers, which are investigated frequently and have shown clinical relevance, could possibly provide useful information in predicting recurrence and provide useful prognostic information. So far none of the biomarkers for bladder cancer are adopted in the UK standard practice. Despite that the Food and Drug Administration (FDA had approved some of these biomarkers, none of the urology associations incorporated them in to their guidelines as yet. However, it won’t be long before a final consensus is reached to integrate molecular staging in to the current TNM staging system.

  7. 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.

  8. 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. PMID:26398114

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

    OpenAIRE

    Ismaili, Nabil; Elkarak, Fadi; Heudel, Pierre Etienne; Flechon, Aude; Droz, Jean Pierre

    2008-01-01

    Background: Small cell bladder carcinoma is an uncommon tumor. In this retrospective study we report our experience dealing with this disease at the Leon-Berard Cancer Centre. Materials and Methods: We retrospectively analyzed various characteristics of small cell bladder carcinoma: patient demographics, histological diagnosis, disease stage, treatment effects and outcome, in 14 non-metastatic small cell bladder carcinoma patients treated at our institution between 1995 and 2006. Results: The...

  10. Clinical impact of bladder biopsies with TUR-BT according to cytology results in patients with bladder cancer: a case control study

    Directory of Open Access Journals (Sweden)

    Matsumoto Kazuhiro

    2010-06-01

    Full Text Available Abstract Background There seems to be no consensus concerning taking bladder biopsies during transurethral resection of bladder tumor (TUR-BT. We investigate the clinical significance of bladder biopsy with TUR-BT and the relationship between urinary cytology and the biopsy results. Methods We reviewed a total of 424 patients with non-muscle invasive bladder cancer treated with TUR-BT between 1998 and 2005. Of the total, 293 patients also underwent a bladder biopsy. Biopsies from suspicious-appearing urothelium (N = 59 and those from normal-appearing urothelium (N = 234 were evaluated separately. Results Bladder cancer was observed in 23 cases (39.0% who underwent a biopsy of suspicious-appearing urothelium. Among these 23 cases, 9 cases with visible tumor resection had carcinoma in situ (CIS only in the biopsies from suspicious-appearing urothelium. Urinary cytology was negative in 3 of the 9 cases. Bladder cancer was observed in 26 cases (11.1% who underwent a biopsy of normal-appearing urothelium. Of them, 5 cases with visible tumors had CIS only in the multiple biopsies from normal-appearing urothelium. Urinary cytology was positive in all of the 5 cases. No upstaging or upgrading cases were found in these patients by the addition of these two types of biopsy. Furthermore, therapy was not altered in these patients. With or without bladder biopsy was not a significant factor for tumor recurrence in either the univariate or multivariate analysis. Conclusions Based on the results, it is concluded the multiple biopsies from normal-appearing urothelium are not necessary in patients with negative cytology results because of the low detection rate and lack of influence on therapeutic decisions. Meanwhile, biopsy of suspicious-appearing urothelium is needed in patients with negative cytology results in order to detect CIS due to staging properties. This result supports a recent EAU guideline.

  11. 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 ...

  12. 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...

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

    Directory of Open Access Journals (Sweden)

    Nehru

    2015-04-01

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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. Analysis of the interaction of extracellular matrix and phenotype of bladder cancer cells

    International Nuclear Information System (INIS)

    The extracellular matrix has a major effect upon the malignant properties of bladder cancer cells both in vitro in 3-dimensional culture and in vivo. Comparing gene expression of several bladder cancer cells lines grown under permissive and suppressive conditions in 3-dimensional growth on cancer-derived and normal-derived basement membrane gels respectively and on plastic in conventional tissue culture provides a model system for investigating the interaction of malignancy and extracellular matrix. Understanding how the extracellular matrix affects the phenotype of bladder cancer cells may provide important clues to identify new markers or targets for therapy. Five bladder cancer cell lines and one immortalized, but non-tumorigenic, urothelial line were grown on Matrigel, a cancer-derived ECM, on SISgel, a normal-derived ECM, and on plastic, where the only ECM is derived from the cells themselves. The transcriptomes were analyzed on an array of 1186 well-annotated cancer derived cDNAs containing most of the major pathways for malignancy. Hypervariable genes expressing more variability across cell lines than a set expressing technical variability were analyzed further. Expression values were clustered, and to identify genes most likely to represent biological factors, statistically over-represented ontologies and transcriptional regulatory elements were identified. Approximately 400 of the 1186 total genes were expressed 2 SD above background. Approximately 100 genes were hypervariable in cells grown on each ECM, but the pattern was different in each case. A core of 20 were identified as hypervariable under all 3 growth conditions, and 33 were hypervariable on both SISgel and Matrigel, but not on plastic. Clustering of the hypervariable genes showed very different patterns for the same 6 cell types on the different ECM. Even when loss of cell cycle regulation was identified, different genes were involved, depending on the ECM. Under the most permissive conditions

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

    Science.gov (United States)

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

    1996-08-01

    A hybrid drug [N-2-chloroethylnitrosoureidodaunorubicin (AD312)] that combines structural and functional features of both anthracyclines and nitrosoureas was evaluated in a preclinical survival model of human bladder cancer. To measure the therapeutic activity of AD312, UCRU-BL13 transitional cell carcinoma cells were grown as xenografts in nude mice, and tumor growth rates were compared after i.v. administration of the drug at three dose levels. AD312 treatment at 45 and 60 mg/kg achieved 7-10-fold inhibition of tumor growth and increased host survival by 156 and 249%, respectively. Doses of 60 mg/kg showed optimal therapeutic efficacy, with sustained tumor growth inhibition, an over 2-fold increase in life span, and 40% of mice tumor free ("cured") at 120 days. Tumors were unresponsive to maximum tolerated doses of doxorubicin, a standard anthracycline used as a single agent and in combination therapies for bladder cancer. 1,3-Bis-[2-chloroethyl]-1-nitrosourea was used as a control for the apparently enhanced response of human tumors in murine hosts to nitrosoureas. 1, 3-Bis-[2-chloroethyl]-1-nitrosourea administered in three injections of 20 mg/kg did not cure mice but temporarily inhibited tumor growth by 70% and prolonged survival by 55%; its activity in this model suggests that it may be included in the repertoire of alkylating agents currently used for treatment of bladder cancers. AD312 showed increased antitumor activity with less toxicity than doxorubicin, and its bifunctional properties provide the opportunity for simultaneous treatment of individual cancer cells with two cytotoxic modalities as well as treatment of heterogeneous populations typical of bladder cancers. This novel cytotoxic drug cured doxorubicin-refractory disease and should be investigated for the clinical management of bladder cancer. PMID:9816302

  2. 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

  3. Benign Prostatic Hyperplasia and the Risk of Prostate Cancer and Bladder Cancer: A Meta-Analysis of Observational Studies.

    Science.gov (United States)

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

    2016-05-01

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

  4. 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.

  5. 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...

  6. Radiotherapy is an effective treatment for high-risk T1-bladder cancer

    International Nuclear Information System (INIS)

    Purpose: Current treatment options for high-risk superficial T1-bladder cancer (Grade 3, associated Tis, multifocality, tumor diameter>5 cm or multiple recurrences) include early cystectomy or the goal of organ preservation by adjuvant intravesical therapy after transurethral resection (TURB). We have evaluated the efficacy of adjuvant radiotherapy or radiochemotherapy on local control, bladder preservation, recurrence rate and long-term survival after TURB of high-risk T1-bladder cancer. Patients and Methods: From May 1982 to May 1999, a total of 74 patients with T1-bladder cancer were treated by either radiotherapy (n=17) or concomitant radiochemotherapy (n=57) after TURB. Radiotherapy was initiated 4 to 8 weeks after TURB; a median dose of 54 (range; 45 to 60) Gy was applied to the bladder with daily fractions of 1.8 to 2.0 Gy. Since 1985 chemotherapy has been given in the 1st and 5th week of radiotherapy and consisted of cisplatin (25 mg/m2/d) in 33 patients, carboplatin (65 mg/m2/d) was administered in 14 patients with decreased creatine clearance (2/d) and 5-fluorouracil (600 mg/m2/d) was applied to 10 patients. Salvage cystectomy was recommended for patients with refractory disease or invasive recurrences. At the time of analysis, the median follow-up for surviving patients was 57 (range: 3 to 174) months. Results: After radiotherapy/radiochemotherapy, a complete remission at restaging TURB was achieved in 62 patients (83.7%), 35 of whom (47% with regard to the total cohort of the 74 treated patients) have been continuously free of tumor, 11 patients (18%) experienced a superficial relapse and 16 patients (26%) showed tumor progression after initial complete response. Overall-survival was 72% at 5 years and 50% at 10 years with 77% of the surviving patients maintaining their own bladder at 5 years. Negative prognostic factors for cancer-specific survival were non-complete (R1/2) initial TURB (p=0.12) and recurrent disease (p=0.07); combined radiochemotherapy

  7. 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

  8. 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...

  9. 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.

  10. 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

  11. 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)

  12. 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...

  13. Intracavitary cobalt-60 irradiation in the prophylactic treatment of bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Tadashi; Kigure, Teruaki; Miyagata, Shigeru (Akita Univ. (Japan). School of Medicine) (and others)

    1992-05-01

    This paper describes the technique and preliminary clinical results of transurethral intracavitary whole bladder mucosal irradiation (IWI) for the prophylaxis of bladder cancer. In this procedure, first, the balloon catheter (22 Fr.) is inserted into the bladder, and next the balloon is inflated with 100 ml of air. Then a Co-60 pellet with about 110 GBq of activity is driven into the center of the bladder. With this method, we can irradiate the whole bladder mucosa almost equally. From April 1985, 36 patients with recurrent tumor and 26 patients with primary and multiple tumors of the bladder have been treated with IWI after transurethral resection or microwave coagulation of the tumors. Tumor stage and grade were as follows: Tis (7), T{sub a}, T{sub 1} (41), T{sub 2} (14), G1 (16), G2 (30) and G3 (16). The tumors were transitional cell carcinoma in all patients. IWI was performed once a week, usually 3 to 5 times, depending on the patients. The total dose to the bladder mucosa ranged from 20 to 58.5 Gy with an average dose of 37.6 Gy. Recurrence rates before and after IWI were calculated using the following formula: recurrence rates (RR)=(total number of recurrences/total months of follow up)x100. RR in the 36 patients with recurrent tumor was 14.0 before IWI and 1.8 after IWI (mean follow up 37.6 mos.). RR in the 26 patients with multiple tumors was 1.4 after IWI (mean follow up 34.8 mos.). RR in patients with G1, G2 and G3 tumors were 1.2, 1.7 and 2.2. The most common side effect was temporary urinary frequency observed in 36 patients (52.9%). Three patients had contracted bladder, and two had hydronephrosis. However, proctitis or incontinence was not evident. Although the preliminary clinical results suggest that our new technique is an effective prophylactic treatment for bladder cancer, further investigation is needed to determine its efficacy. (author).

  14. Immunotherapy of murine bladder cancer by irradiated tumor vaccine

    Energy Technology Data Exchange (ETDEWEB)

    Lamm, D.L.; Riggs, D.R.; DeHaven, J.I.; Bryner, R.W. (West Virginia Univ. School of Medicine, Morgantown (USA))

    1991-01-01

    This investigation explored the efficacy of irradiated autologous mouse bladder tumor (Ir-MBT2) as an active specific immunotherapeutic agent and as adjuvant therapy with Bacillus Calmette-Guerin (BCG) against a subcutaneously transplanted murine bladder tumor. Tumor incidence was significantly reduced in groups receiving BCG (27%, p less than 0.005) or Ir-MBT2 with BCG (53%, p less than 0.025), compared to control (93%). Survival was significantly improved in groups treated with BCG (100%, p less than 0.005), 10(5) Ir-MBT2 with BCG (53%, p less than 0.01), or 10(7) Ir-MBT2 with BCG (47%, p less than 0.025) compared with control (13%). Surprisingly, Ir-MBT2 consistently reduced the efficacy of BCG alone. Ir-MBT2 alone (10(7)) appeared to enhance tumor growth. Autologous irradiated bladder tumor vaccine, alone or in combination with BCG, displayed no immunotherapeutic advantage. The use of irradiated tumor cell vaccine for bladder cancer therapy may reduce the results achievable with BCG alone.

  15. Immunotherapy of murine bladder cancer by irradiated tumor vaccine

    International Nuclear Information System (INIS)

    This investigation explored the efficacy of irradiated autologous mouse bladder tumor (Ir-MBT2) as an active specific immunotherapeutic agent and as adjuvant therapy with Bacillus Calmette-Guerin (BCG) against a subcutaneously transplanted murine bladder tumor. Tumor incidence was significantly reduced in groups receiving BCG (27%, p less than 0.005) or Ir-MBT2 with BCG (53%, p less than 0.025), compared to control (93%). Survival was significantly improved in groups treated with BCG (100%, p less than 0.005), 10(5) Ir-MBT2 with BCG (53%, p less than 0.01), or 10(7) Ir-MBT2 with BCG (47%, p less than 0.025) compared with control (13%). Surprisingly, Ir-MBT2 consistently reduced the efficacy of BCG alone. Ir-MBT2 alone (10(7)) appeared to enhance tumor growth. Autologous irradiated bladder tumor vaccine, alone or in combination with BCG, displayed no immunotherapeutic advantage. The use of irradiated tumor cell vaccine for bladder cancer therapy may reduce the results achievable with BCG alone

  16. UBE2C is a marker of unfavorable prognosis in bladder cancer after radical cystectomy

    OpenAIRE

    Morikawa, Teppei; Kawai, Taketo; Abe, Hiroyuki; Kume, Haruki; Homma, Yukio; Fukayama, Masashi

    2013-01-01

    It has been suggested that ubiquitin-conjugating enzyme E2C (UBE2C, also known as UBCH10) represents a promising cancer biomarker. However, the clinicopathological or prognostic significance as well as the functions of UBE2C in bladder cancer are largely unknown. To investigate the significance of UBE2C expression in bladder cancer, immunohistochemical analysis was performed using a tissue microarray. UBE2C positivity was observed in 51 of 82 (62%) bladder urothelial carcinoma cases treated w...

  17. 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...

  18. Sequential gemcitabine and tamoxifen treatment enhances apoptosis and blocks transformation in bladder cancer cells

    OpenAIRE

    TAKEUCHI, HISASHI; MMEJE, CHINEDU O.; Goodwin G. Jinesh; TAOKA, RIKIYA; Kamat, Ashish M.

    2015-01-01

    Bladder cancer is a common malignancy for which regional or metastatic disease is identified at diagnosis. The aim of this study was to determine whether tamoxifen (Tam), an estrogen receptor (ER) antagonist, can sensitize bladder cancer cell lines to gemcitabine (Gem) chemotherapy. ERα and ERβ protein levels were determined in each cell line using western blot analysis. The TCC-Sup, 5637, and RT4 bladder cancer cells were exposed to various concentrations and regimens of Tam or Gem alone or ...

  19. 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.

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

    International Nuclear Information System (INIS)

    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

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Lucio Dell’Atti

    2015-03-01

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

  3. Interleukin-4 receptor alpha overexpression in human bladder cancer correlates with the pathological grade and stage of the disease

    International Nuclear Information System (INIS)

    Previously, we have demonstrated that interleukin-4 receptor α (IL-4Rα) is overexpressed on a variety of human cancers and can serve as target for IL-4 immunotoxin comprised of IL-4 and a mutated Pseudomonas exotoxin. However, its expression and association with grade and clinical stage of bladder cancer has not been studied. IL-4Rα expression was examined in human bladder cancer cell lines, mouse xenografts, and biopsy specimens at mRNA and protein levels by real-time RT-PCR and IHC/ISH techniques. We also examined the effect of IL-4 on proliferation and invasion of bladder carcinoma cell lines. For tissue microarray (TMA) results, we analyzed the precision data using exact binomial proportion with exact two-sided P-values. We used Cochran–Armitage Statistics with exact two-sided P-values to examine the trend analysis of IL-4Rα over grade or stage of the bladder cancer specimens. The influence of age and gender covariates was also analyzed using multiple logistic regression models. IL-4Rα is overexpressed in five bladder cancer cell lines, while normal bladder and human umbilical vein cell lines (HUVEC) expressed at low levels. Two other chains of IL-4 receptor complex, IL-2RγC and IL-13Rα1, were absent or weakly expressed. IL-4 modestly inhibited the cell proliferation, but enhanced cell invasion of bladder cancer cell lines in a concentration-dependent manner. Bladder cancer xenografts in immunodeficient mice also maintained IL-4Rα overexpression in vivo. Analysis of tumor biopsy specimens in TMAs revealed significantly higher IL-4Rα immunostaining (≥2+) in Grade 2 (85%) and Grade 3 (97%) compared to Grade 1 tumors (0%) (P ≤ 0.0001). Similarly, 9% stage I tumors were positive for IL-4Rα (≥2+) compared to 84% stage II (P ≤ 0.0001) and 100% stages III–IV tumors (P ≤ 0.0001). IL-13Rα1 was also expressed in tumor tissues but at low levels and it did not show any correlation with the grade and stage of disease. However, the IL-2RγC was not

  4. Intraoperative radiation therapy in patients with bladder cancer. A review of techniques allowing improved tumor doses and providing high cure rates without loss of bladder function

    International Nuclear Information System (INIS)

    Conventional external beam irradiation, using modern megavoltage techniques and doses that do not harm bladder function, will permanently eradicate local bladder cancer in 30% to 50% of patients, compared with 70% to 90% with cystectomy. In appropriately chosen patients, open surgery can safely provide excellent exposure for the selective delivery of more radiant energy directly to the tumor and less to the uninvolved portion of the bladder. Intraoperative radiation therapy, by either a removable radium or iridium implant or a large single dose of electrons, has been reported to be safe and can permanently cure the bladder of cancer and also preserve bladder function in more than 75% of patients with solitary tumors that invade into but not beyond the bladder muscle. With the increasing interest in and availability of intraoperative radiation therapy in the US, this curative and bladder-sparing treatment for operable patients with bladder cancer invading the trigone is appropriate for careful clinical trial. 13 references

  5. 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.

  6. 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....

  7. 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

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

    Institute of Scientific and Technical Information of China (English)

    白银; 王琰; 周丽君; 俞莉章

    2001-01-01

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

  9. Understanding the gender disparity in bladder cancer risk: The impact of sex hormones and liver on bladder susceptibility to carcinogens

    OpenAIRE

    Zhang, Yuesheng

    2013-01-01

    It has long been known that bladder cancer (BC) incidence is approximately 4-fold higher in men than in women in the US, and a similar disparity also exists in other countries. The reason for this phenomenon is not known, which impedes progress in BC prevention. However, BC incidence is also significantly higher in male animals than in their female counterparts after treatment with aromatic amines, which are principal human bladder carcinogens. These animal studies and related studies in the ...

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

    International Nuclear Information System (INIS)

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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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.

  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. The role of partial cystectomy in treatment of muscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Kojić D.

    2007-01-01

    Full Text Available Muscle invasive bladder cancer is usually treated by radical cystectomy, but in some selected cases with solitary tumor with appropriate localization partial cystectomy can be the treatment of choice achieving long term results with bladder preservation. We reviewed records of 11 patients which were treated in 5 year period from June 2002 to June 2007. by partial cystectomy according to the size of the tumor, localization, histology, multifocality, pathological and clinical stage, sex, and age. Male: female ratio was 6:5, mean age of the patients being 64.9 years. All patients bur one had solitary lesions located in the bladder dome in 4, on lateral sides in 5,2 patients had a tumor in diverticulum. TCC gr II was diagnosed 6 pts, TCC gr III in 5. One patient died in a year from disease progression, one from other reason, while all other patients are alive and disease free, the longest disease free interval being 3 years. Bladder capacity is adequate in all patients resulting in good quality of life .Our results suggest that in selected patients cancer control can be achieved with partial cystectomy.

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

    OpenAIRE

    Andersen, J. B.; Aaboe, M; Borden, E C; Goloubeva, O G; Hassel, B. A.; Ørntoft, T F

    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....

  20. Possible disease remission in patient with invasive bladder cancer with D-fraction regimen

    OpenAIRE

    Rajamahanty, Srinivas; Louie, Brandon; O’Neill, Cormac; Choudhury, Muhammad; Konno, Sensuke

    2009-01-01

    Superficial bladder tumors are the most prevalent form of bladder cancers and transurethral resection is the primary surgical modality for those tumors. However, nearly 65% of patients will have tumor recurrence in five years while about 15% will have progression to muscle invasion. Thus, the primary therapeutic aim is to prevent multiple recurrences and progression to a more advanced, invasive disease. We here report an 87-year-old white male patient with invasive bladder cancer who received...

  1. 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.

  2. 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.

  3. 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...

  4. 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...

  5. Combined-modality treatment and organ preservation in bladder cancer. Do molecular markers predict outcome?

    International Nuclear Information System (INIS)

    Purpose: in invasive bladder cancer, several groups have reported the value of organ preservation by a combined-treatment approach, including transurethral resection (TUR-BT) and radiochemotherapy (RCT). As more experience is acquired with this organ-sparing treatment, patient selection needs to be optimized. Clinical factors are limited in their potential to identify patients most likely to respond to RCT, thus, additional molecular markers for predicting treatment response of individual lesions are sorely needed. Patients and methods: the apoptotic index (AI) and Ki-67 index were evaluated by immunohistochemistry on pretreatment biopsies of 134 patients treated for bladder cancer by TUR-BT and RCT. Expression of each marker as well as clinicopathologic factors were then correlated with initial response, local control and cancer-specific survival with preserved bladder in univariate and multivariate analysis. Results: the median AI for all patients was 1.5% (range 0.2-7.4%). The percentage of Ki-67-positive cells in the tumors ranged from 0.2% to 85% with a median of 14.2%. A significant correlation was found for AI and tumor differentiation (G1/2: AI = 1.3% vs. G3/4: AI = 1.6%; p = 0.01). A complete response at restaging TUR-BT was achieved in 76% of patients. Factors predictive of complete response included T-category (p < 0.0001), resection status (p = 0.02), lymphovascular invasion (p = 0.01), and Ki-67 index (p = 0.02). For local control, AI (p = 0.04) and Ki-67 index (p = 0.05) as well as T-category (p = 0.005), R-status (p = 0.05), and lymphatic vessel invasion (p = 0.05) reached statistical significance. Out of the molecular markers only high Ki-67 levels were associated to cause-specific survival with preserved bladder. On multivariate analysis, T-category was the strongest independent factor for initial response, local control and cancer-specific survival with preserved bladder. Conclusion: The indices of pretreatment apoptosis and Ki-67 predict a

  6. 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

  7. More Evidence Diabetes Drug Actos Raises Bladder Cancer Risk a Bit

    Science.gov (United States)

    ... gov/medlineplus/news/fullstory_158051.html More Evidence Diabetes Drug Actos Raises Bladder Cancer Risk a Bit But odds are small, and ... or federal policy. More Health News on: Bladder Cancer Diabetes Medicines Drug Reactions Recent Health News Related MedlinePlus ...

  8. Opportunities of radiological methods for examination in diagnostics of urinary bladder cancer

    OpenAIRE

    Chekhonatskaya M.L.; Popkov V.M.; Zuev V.V.; Glybochko P.V.; Ponukalin A.N.

    2011-01-01

    The research goal is the comparative analysis of Russian and foreign studies concerned the possibility of radiological methods of diagnostics of cancer of urinary bladder. The problem of early diagnostics of initial tumor and tumor recurrence, determination of stages of bladder cancer, its prognosis and outcome remains an actual one

  9. Clinical pitfalls in diagnosis of nonmuscle-invasive bladder cancer.

    Science.gov (United States)

    Serretta, Vincenzo; Scalici Gesolfo, Cristina

    2015-10-01

    Current global economic crisis imposes healthcare system to reduce unnecessary investigations and increase early detection of tumors, to decrease the costs of an advanced disease. Several diagnostic pitfalls may occur dealing with bladder cancer (BC), particularly in nonmuscle-invasive (NMIBC) one. Hematuria, the commonest sign in NMIBC, is often underestimated. Urinary cytology is highly specific for high-grade tumors, but has a low sensitivity for low-grade BC, is operator dependent, and not always obtainable in clinical practice. Numerous urinary tests are available to ameliorate the accuracy of cytology, but none of them is routinly used in urological practice. Ultrasound could hardly detect a small bladder tumor, especially if located in the bladder neck or in the anterior wall. Computed tomography (CT) is widely adopted as an alternative to conventional urography, but its usefulness in patients with hematuria is still debated. MRI has a higher accuracy than CT for staging BC and evaluate the bladder-wall invasion. A negative cystoscopy cannot exclude Tis and should be accompanied by urinary cytology in patients with suspected Tis or high-risk NMIBC; however, new techniques such as narrow band imaging (NBI) and photodynamic (PDD) increase the detection rate of BC and flat lesions. Nearly half of all diagnostic resections present omission of muscle in the specimen or its mention in the pathology report, which is associated with an increased mortality. An adequate muscle sampling during endoscopic resection is mandatory, particularly in patients with high-grade disease. Recognition of pitfalls in diagnosis and management of BC represents the first step for a correct approach. PMID:26481718

  10. A case of bladder cancer following adjuvant external beam radiation for prostate cancer

    International Nuclear Information System (INIS)

    A 57-year-old male with a history of right renal cell carcinoma was diagnosed with prostate carcinoma associated with a high prostatic specific antigen (PSA) level (5.2 ng/ml). Histological examination of the resected prostate specimen obtained by radical prostatectomy revealed well differentiated adenocarcinoma, Gleason score 3+3, and pT3aN0M0. After six months of observation, an elevation of PSA level was recognized and local recurrence was suspected. Therefore, radiotherapy with a total of 61.2 Gy was administered. Seventeen months later, bladder cancer was diagnosed. It had to be treated with pelvic evisceration because of suspicious heavy adhesions due to prior treatments. Histology findings were urothelial carcinoma in situ, G3, and pTisN0M0. (author)

  11. 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

  12. 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

  13. 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

  14. Prognostic value of radical cystoprostatectomy in men with bladder cancer infiltrating prostate versus co-existing prostate cancer: a research study

    Directory of Open Access Journals (Sweden)

    Prokopowicz Grzegorz

    2010-09-01

    Full Text Available Abstract Background The aim of the following study is to evaluate the advancement of incidentally diagnosed prostate cancer in specimen after cystoprostatectomies caused by muscle-invasive bladder cancer. Secondly we assessed the survival in patients after radical cystoprostatectomy whose postoperative specimen was characterized by the presence of co-existing prostate cancer or prostate infiltration by urothelial bladder cancer. Methods Between 1993 and 2009 a total of 320 patients with muscle-invasive bladder cancer underwent cystoprostatectomy. The first analyzed group consisted of 52 patients with bladder cancer infiltrating prostate, while the second group consisted of 21 patients with co-existing prostate cancer. In all patients cancer specific survival and progression were analyzed. Average follow up was 75.2 months (range: 0 - 181. Results Cancer-specific survival was significantly shorter in group I (p = 0.03. Neoplastic progression in patients from group I was observed in 42.2% of patients, while in patients from group II in 23.6% of patients (p = 0.04. No statistical difference was observed in the percentage of positive lymph nodes between the groups (p = 0.22. The median Gleason score in patients with co-existing prostate cancer was equal to 5. The stage of prostate cancer pT2/pT3 was equal to 20 (96%/1 (4% patients. 12 (57% prostate cancers were clinically insignificant. Biochemical recurrence occurred in 2 (9% patients. Conclusions 1. Incidentally diagnosed prostate cancer in specimen after cystoprostatectomies is frequently clinically insignificant and characterized by low progression. 2. Patients with bladder cancer infiltrating prostate are characterized by higher percentage of progression and death in comparison with patients with co-existing prostate cancer.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  16. Analysis of the radiation related morbidity observed in a randomized trial of neutron therapy for bladder cancer

    International Nuclear Information System (INIS)

    This report is an analysis of the morbidity in the bladder and bowel observed in a randomized trial of d(15)+Be neutrons versus megavoltage photons in the treatment of bladder cancer. Acute reactions in the bladder and bowel were significantly worse after photon therapy. Of the patients treated with photons 45.7% had severe reactions in the bladder compared with 10.6% after neutron therapy (p less than 0.001). Severe acute bowel reactions were observed in 8.5% of the patients after photon therapy compared with 3.8% after neutron therapy (p less than 0.05). Late reactions were significantly worse after neutrons. Severe late reactions in the bladder were seen in 58.5% of patients after neutron therapy and in 40.5% after photon therapy (p less than 0.05). In the bowel they were observed in 53.3% of patients after neutron therapy compared with 8% after photon therapy (p less than 0.0001). The disparity in the degree of early and late complications makes assessment of RBE values difficult. It is estimated that for bladder morbidity the RBE value, for photon dose fractions of 2.75 Gy, is less than 3.3 for early reactions and equal to 3.4 for late effects. The respective RBE values for early and late effects in the bowel are less than 3.4 and 3.8

  17. 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

  18. Diagnostic value of circulating tumor cell detection in bladder and urothelial cancer: systematic review and meta-analysis

    International Nuclear Information System (INIS)

    The diagnostic value and prognostic significance of circulating tumor cell (CTC) detection in patients with bladder cancer is controversial. We performed a meta-analysis to consolidate current evidence regarding the use of CTC detection assays to diagnose bladder and other urothelial cancers and the association of CTC positivity with advanced, remote disease. Studies that investigated the presence of CTCs in the peripheral blood of patients with bladder cancer and/or urothelial cancer were identified and reviewed. Sensitivities, specificities, and positive (LR+) and negative likelihood ratios (LR-) of CTC detection in individual studies were calculated and meta-analyzed by random effects model. Overall odds ratio of CTC positivity in patients with advanced disease versus those with organ-confined cancer was also calculated. Overall sensitivity of CTC detection assays was 35.1% (95%CI, 32.4-38%); specificity, LR+, and LR- was 89.4% (95%CI, 87.2-91.3%), 3.77 (95%CI, 1.95-7.30) and 0.72 (95%CI, 0.64-0.81). CTC-positive patients were significantly more likely to have advanced (stage III-IV) disease compared with CTC-negative patients (OR, 5.05; 95%CI, 2.49-10.26). CTC evaluation can confirm tumor diagnosis and identify patients with advanced bladder cancer. However, due to the low overall sensitivity, CTC detection assays should not be used as initial screening tests

  19. Diagnostic value of circulating tumor cell detection in bladder and urothelial cancer: systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Koutsilieris Michael

    2011-08-01

    Full Text Available Abstract Background The diagnostic value and prognostic significance of circulating tumor cell (CTC detection in patients with bladder cancer is controversial. We performed a meta-analysis to consolidate current evidence regarding the use of CTC detection assays to diagnose bladder and other urothelial cancers and the association of CTC positivity with advanced, remote disease. Methods Studies that investigated the presence of CTCs in the peripheral blood of patients with bladder cancer and/or urothelial cancer were identified and reviewed. Sensitivities, specificities, and positive (LR+ and negative likelihood ratios (LR- of CTC detection in individual studies were calculated and meta-analyzed by random effects model. Overall odds ratio of CTC positivity in patients with advanced disease versus those with organ-confined cancer was also calculated. Results Overall sensitivity of CTC detection assays was 35.1% (95%CI, 32.4-38%; specificity, LR+, and LR- was 89.4% (95%CI, 87.2-91.3%, 3.77 (95%CI, 1.95-7.30 and 0.72 (95%CI, 0.64-0.81. CTC-positive patients were significantly more likely to have advanced (stage III-IV disease compared with CTC-negative patients (OR, 5.05; 95%CI, 2.49-10.26. Conclusions CTC evaluation can confirm tumor diagnosis and identify patients with advanced bladder cancer. However, due to the low overall sensitivity, CTC detection assays should not be used as initial screening tests.

  20. 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.

  1. 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...

  2. 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.

  3. Perioperative search for circulating tumor cells in patients undergoing radical cystectomy for bladder cancer

    Directory of Open Access Journals (Sweden)

    Karl A

    2009-11-01

    obtained before surgery (analyzed blood volume was 25 mL. There was one CTC detected in the blood sample that was obtained during surgical removal of the urinary bladder (analyzed blood volume was 27 mL. There was no rise in the amount of CTCs during surgical procedure. The final pathological report of this patient showed an advanced tumor stage (T3b, N0, R1. In the other patients, no CTCs were detected at all, neither before rCX nor right after surgical removal of the bladder. Pathological stage for these patients ranged from pT1m G3 -pT2b G3. None of these patients showed lymph node involvement. An average of 14.6 lymph nodes (5-40 LNs were obtained. OR time to surgical removal of the urinary bladder ranged from 60 minutes to 150 minutes (mean 82 min.. Conclusions Although only a very small group of patients was analyzed in this study, the presence of CTCs seems to be correlated with an advanced tumor stage. Therefore the detection of CTCs could be used for an optimized assessment of a patient's disease status in urothelial cancer. A further aim of this study was to assess whether surgical manipulation during radical cystectomy is associated with a release of CTCs into the vascular system. None of the patients who were negative for CTCs before surgery showed CTCs during surgical removal of the bladder, suggesting that there was no release of CTCs during surgery. However, further study is needed to prove these findings and evaluate the significance of CTCs as an indicator for therapeutic decisions.

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

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    Guadalupe Lorenzatti Hiles

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

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

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    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)

  6. 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 ...

  7. 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

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    F. Sh. Engalychev

    2014-08-01

    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.

  10. 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

  11. 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

  12. 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。

  13. FDG-PET for preoperative staging of bladder cancer

    International Nuclear Information System (INIS)

    The presence of lymph node involvement (N) and distant metastasis (M) in patients with invasive bladder carcinoma is a major determinant of survival and, therefore, a pivotal element in the therapeutic management. The aim of this prospective study was to evaluate the use of18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in this indication. Whole-body FDG-PET and computed tomography (CT) were performed in 55 patients with non-metastatic invasive bladder cancer for preoperative staging. Correlative imaging of PET with CT was performed, leading to a PET(CT) result. The imaging results were compared with the gold standard, consisting of histopathology (lymphadenectomy, guided biopsy) or clinical follow-up for 12 months, and related to overall survival using the Kaplan-Meier method. The gold standard was available in 40 patients and indicated NM-positive disease in 15 patients (12 N lesions, 8 M lesions), and NM-negative disease in 25 patients. For the diagnosis of NM-positive disease, the sensitivity, specificity and accuracy of PET(CT) were 60%, 88% and 78%, respectively. Diagnostic discordances between PET(CT) and CT alone were found in 9/40 patients, among whom PET was correct in six (15%): three with true-positive and one with true-negative distant metastases, and two with true-negative lymph nodes. Median survival time of patients in whom PET(CT) indicated NM-positive disease was 13.5 months, compared with 32.0 months in the patients with a NM-negative PET(CT) (p=0.003). Addition of metabolism-based information provided by FDG-PET to CT in the preoperative staging of invasive bladder carcinoma yields a high diagnostic and prognostic accuracy. (orig.)

  14. Changes in Immunogenicity during the Development of Urinary Bladder Cancer: A Preliminary Study

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    Wojciech Jóźwicki

    2016-02-01

    Full Text Available In the present study, we evaluated tumor-infiltrating lymphocytes (TILs and blood regulatory T lymphocyte (Tregs, CD4+/CD25+/FoxP3+ expression in bladder cancer patients. The number of CD4+, CD8+, CD25+, FoxP3+ and CD20+ TILs was analyzed in association with clinico-pathomorphological features. In more advanced metastasizing tumors, showing non-classic differentiation (ND and a more aggressive tissue invasion type (TIT, the number of TILs decreased. A low number of CD4+ TILs was associated with poor prognosis. Similarly, Treg frequency before surgery and after surgical treatment was significantly lower in more advanced tumors. The changes in TILs, as well as of local and systemic Tregs, were accompanied by changes in the histological phenotype of urothelial carcinoma regarding pT stage, NDs, TIT, and clinical outcomes. The number of TILs and the frequency of blood Tregs (indicators of antitumor response may be essential for choosing an immunotherapy that is adjusted to the immune status according to the phase of tumor growth. Moreover, a significant reduction in the number of CD4+ and CD8+ TILs with the development of NDs in more advanced tumors may be associated with lower tumor immunogenicity, resulting in immune tolerance towards tumor tissue. These observations and the tendency of urothelial bladder carcinoma to undergo NDs in a heterogeneous manner during tumor progression suggest complex interactions between bladder cancer immunogenicity and stages of tumor progression.

  15. HIF-1α activates hypoxia-induced PFKFB4 expression in human bladder cancer cells.

    Science.gov (United States)

    Zhang, Hao; Lu, Chengyin; Fang, Meng; Yan, Wangjun; Chen, Mo; Ji, Yingzheng; He, Shaohui; Liu, Tielong; Chen, Tianrui; Xiao, Jianru

    2016-07-29

    PFKFB4 is reported to regulate glycolysis by synthesizing fructose-2, 6-bisphosphate (F2,6BP) and has proved to be associated with most malignancies. However, the underlying mechanism for increased PFKFB4 expression in bladder cancer remains unclear. The present study demonstrated that PFKFB4 was overexpressed in bladder cancer tissues. In addition, the expression of PFKFB4 elevated in bladder cancer cells in the hypoxic condition, while in nomoxic condition, the expression of PFKFB4 still very low. Furthermore, we identified the hypoxia-responsive elements (HRE)-D from five putative HREs in the promoter region of PFKFB4 and demonstrated that the HRE-D was transactivated by the HIF-1α in bladder cancer cells. By using the Double-immunofluorescence co-localization assay, we revealed that the HIF-1α expression was associated with PFKFB4 expression in human bladder cancer specimens. Altogether, our study for the first time identified the pivotal role of HIF-1α in the connection between PFKFB4 and hypoxia in bladder cancer, which may prove to be a potential target for the treatment of bladder cancer. PMID:27181362

  16. 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

  17. Treatment results of radiation therapy for muscle-invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Langsenlehner, Tanja; Doeller, Carmen; Stranzl-Lawatsch, Heidi; Kapp, Karin S. [Univ. Clinic of Therapeutic Radiology and Oncology, Medical Univ. of Graz (Austria); Quehenberger, Franz [Inst. for Medical Informatics, Statistics and Documentation, Medical Univ. of Graz (Austria); Langsenlehner, Uwe [Internal Outpatient Dept., Steiermaerkische GKK, Graz (Austria); Pummer, Karl [Dept. of Urology, Medical Univ. of Graz (Austria)

    2010-04-15

    Purpose: To assess local control and survival rates in patients with muscle-invasive bladder cancer treated with external-beam radiotherapy and to investigate prognostic factors. Patients and methods: Between 1997 and 2007, 75 patients (male, n = 58; female, n = 17, median age, 74.2 years) with localized transitional cell carcinoma of the bladder (T2, n = 34; T3, n = 32; T4, n = 9) not suitable for radical surgery due to advanced age, comorbidity or inoperability underwent external-beam radiotherapy without simultaneous chemotherapy at the University Clinic of Therapeutic Radiology and Oncology, Medical University of Graz, Austria. A conformal four-field technique was used in all patients to treat the tumor and regional lymph nodes with single daily fractions of 1.8-2 Gy to a total dose of 50-50.4 Gy, followed by a cone-down to encompass the empty bladder which was boosted to 70-70.4 Gy. All patients had undergone transurethral tumor resection prior to radiotherapy which was macroscopically incomplete in 62 patients. Results: Complete response was achieved in 65% of patients. Actuarial 3-year local control and metastases-free survival rates were 52.5% and 63.7%, 3-year local recurrence-free survival rate in complete responders was 71%. In univariate analysis, hydronephrosis, lymph vessel invasion, and macroscopic residual tumor were significantly predictive of disease progression. Hydronephrosis and lymph vessel invasion were also associated with a higher risk of local recurrence. The actuarial 3-year progression-free and overall survival rates were 40.1% and 56.9%, respectively. Conclusion: Radiotherapy is an effective treatment option in terms of local control and survival even in elderly patients with locally advanced bladder cancer not suitable for cystectomy. (orig.)

  18. Inhibitory Role of the Small Leucine-Rich Proteoglycan Biglycan in Bladder Cancer

    OpenAIRE

    Niedworok, Christian; Röck, Katharina; Kretschmer, Inga; Freudenberger, Till; Nagy, Nadine; Szarvas, Tibor; vom Dorp, Frank; Reis, Henning; Rübben, Herbert; Fischer, Jens W

    2013-01-01

    Background Urothelial bladder cancer is the ninth most common cancer. Despite surgical and chemotherapeutic treatment the prognosis is still poor once bladder cancer progresses to a muscle-invasive state. Discovery of new diagnostic markers and pathophysiologic effectors might help to contribute to novel diagnostic and therapeutic options. The extracellular matrix microenvironment shaped by the extracellular matrix critically affects tumor cell and stroma cell functions. Therefore, aim of the...

  19. 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...

  20. Sexual function following radical radiotherapy for bladder cancer

    International Nuclear Information System (INIS)

    Background and purpose: The effect of radical radiotherapy (RT) for bladder cancer on sexual function has not been previously investigated. The current study was designed as a pilot to assess sexual function in males pre- and post-radiotherapy. Materials and methods: An anonymous questionnaire was devised to examine the following sexual domains: libido, frequency of sexual function, erectile capacity, orgasm and ejaculation in the 6 months prior to radiotherapy and following treatment. Serum testosterone, FSH and LH were measured in 10 patients. Results: Eighteen patients completed the questionnaire from 10 to 56 months following irradiation, 13 of whom were able to achieve an erection prior to RT. Over half of these patients noted a decline in the quality of erections after RT, with a similar proportion noting decreased libido and frequency of sexual activity. Three patients lost the ability to have any erections whatsoever. Of the 10 patients retaining erectile capacity, three noted reduced frequency of early morning erections suggesting a physical aetiology, five had decreased frequency of ejaculation and four had reduced intensity of orgasms. Seventy-one percent (12/17) felt their sex life was worse following RT but only 56% (9/16) were concerned about the deterioration. Testosterone levels were normal in all but one patient. Conclusions: Radical RT to the bladder can cause a decrease in sexual function in males. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  1. 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...

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

    Directory of Open Access Journals (Sweden)

    Sarah R. Ambrose

    2015-09-01

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

  3. Detection of human papillomavirus infection and p16 immunohistochemistry expression in bladder cancer with squamous differentiation.

    Directory of Open Access Journals (Sweden)

    Sung Han Kim

    Full Text Available OBJECTIVES: To determine the potential association between HPV infection and the squamous cell component of urothelial carcinoma (UC of the bladder and to validate p16 overexpression as a surrogate marker for HPV infection in these cancers among Koreans. METHODS: We analyzed the presence of HPV infection using an HPV-DNA chip and the expression of p16 using immunohistochemistry in 47 subjects between July 2001 and March 2011. The study group (n = 35 included patients with squamous differentiation of UC of the bladder. The control group (n = 12 included patients with squamous metaplasia of the bladder. RESULTS: Baseline characteristics of control and study groups were similar. HPV DNA detection rates were approximately 2-fold higher in the study than the control group (17.1% [6/35] versus 8.3% [1/12], respectively, but the difference was not statistically significant. P16 overexpression was detected in 16/35 (45.7% study group and 1/12 (8.3% control group samples (p = 0.034. Both HPV-positivity and p16 overexpression were present in 3/35 (8.8% study group samples, but none of the control group (p = 0.295. In the study group, the percentage of HPV-positive cases who were non-smokers was 2-fold higher than the percentage of HPV-negative cases who were non-smokers (66.7% [4/6] versus 31.0% [9/29], respectively; however, statistical significance was not achieved due to the small sample size. CONCLUSIONS: HPV infection may be associated with UC of the bladder with squamous differentiation, especially in non-smokers. However, p16 expression does not appear to be a strong surrogate marker for evidence of HPV infection in this type of cancer.

  4. 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...

  5. 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...

  6. 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...

  7. 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

  8. Immunohistochemical study of the expression of cell cycle regulating proteins at different stages of bladder cancer

    DEFF Research Database (Denmark)

    Primdahl, Hanne; Maase, Hans von der; Sørensen, Flemming B.; Wolf, Hans; Ørntoft, Torben Falck

    2002-01-01

    PURPOSE: The cell cycle is known to be deregulated in cancer. We therefore analyzed the expression of the cell cycle related proteins p21, p27, p16, Rb, and L-myc by immunohistochemical staining of bladder tumors. METHODS: The tissue material consisted of bladder tumors from three groups of...

  9. Immunochemotherapy for advanced bladder cancer using FT-207, adriamycin and OK-432.

    Science.gov (United States)

    Mishina, T; Watanabe, H; Fujiwara, T; Kobayashi, T; Maegawa, M; Nakao, M; Nakagawa, S

    1982-10-01

    A combination therapy consisting of daily intrarectal administration of 1,500 mg of FT-207 suppository, daily or every three day bladder instillation of 40 mg adriamycin for a total of 20 applications, and once per week intramuscular administration of 5 KE OK-432 was described. The therapy was performed in 30 cases of advanced bladder cancer. The effectiveness evaluated by Karnofsky's criteria was as follows: 8 cases of 0-0, 2 of 0-A, 1 of 0-B, 2 of 0-C, 7 of 1-A and 10 of 1-B, showing an effective rate of 57%. Local pain was observed in 20 cases (67%), pancytopenia in 1 (3%), hepatitis in 4 (13%), stomatitis in 5 (17%) and anorexia in 6 (20%). From this clinical trial, it is presumed that combination therapy administering FT-207 intrarectally, adriamycin intravesically and OK-432 intramuscularly might be used for the treatment of advanced bladder cancer provided sufficient care is taken of general side effects. PMID:6817468

  10. 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

  11. 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.

  12. 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.

  13. Invasive bladder cancer: treatment strategies using transurethral surgery, chemotherapy and radiation therapy with selection for bladder conservation

    International Nuclear Information System (INIS)

    Purpose: Combined modality therapy has become the standard oncologic approach to achieve organ preservation in many malignancies. Methods and Materials: Although radical cystectomy has been considered as standard treatment for invasive bladder carcinoma in the United States, good results have been recently reported from several centers using multimodality treatment, particularly in patients with clinical T2 and T3a disease who do not have a ureter obstructed by tumor. Results: The components of the combined treatment are usually transurethral resection of the bladder tumor (TURBT) followed by concurrent chemotherapy and radiation therapy. Following an induction course of therapy a histologic response is evaluated by cystoscopy and rebiopsy. Clinical 'complete responders' (tumor site rebiopsy negative and urine cytology with no tumor cells present) continue with a consolidation course of concurrent chemotherapy and radiation. Those patients not achieving a clinical complete response are recommended to have an immediate cystectomy. Individually the local monotherapies of radiation, TURBT, or multidrug chemotherapy each achieve a local control rate of the primary tumor of from 20 to 40%. When these are combined, clinical complete response rates of from 65 to 80% can be achieved. Seventy-five to 85% of the clinical complete responders will remain with bladders free of recurrence of an invasive tumor. Conclusions: Bladder conservation trials using combined modality treatment approaches with selection for organ conservation by response of the tumor to initial treatment report overall 5-year survival rates of approximately 50%, and a 40-45% 5-year survival rate with the bladder intact. These modern multimodality bladder conservation approaches offer survival rates similar to radical cystectomy for patients of similar clinical stage and age. Bladder-conserving therapy should be offered to patients with invasive bladder carcinoma as a realistic alternative to radical

  14. 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

  15. What is the correct staging and treatment strategy for locally advanced prostate cancer extending to the bladder?

    Directory of Open Access Journals (Sweden)

    Özgür Haki Yüksel

    2015-07-01

    Full Text Available In locally advanced prostate cancer with bladder invasion, frequently encountered problems such as bleeding, urinary retention, hydronephrosis, and pain create distress for the patients. Therefore patients’ quality of life is disrupted and duration of hospitalization is prolonged. Relevant literature about accurate staging and treatment of locally advanced prostate cancer with bladder invasion was investigated. Locally advanced prostate cancer can present as a large-volume aggressive tumor extending beyond boundaries of prostate gland, and involving neighboring structures which can be involved as recurrence(s following initial local therapy. Survival times of these patients can range between 5 and 8 years. Their common characteristics are adverse and severe local symptoms unfavorably affecting quality of life Control of local symptoms and their effective palliation are independent clinical targets influencing survival outcomes of these patients. The treatment outcomes of locally advanced prostate cancer into the bladder are currently debatable. Although in the current TNM classification, it is defined in T4a, we think that this may be categorized as a subgroup of T3 and thus encourage surgeons for the indication of radical surgeries (radical prostatectomy, radical cystoprostatectomy in selected patient populations after discussing issues concerning consequences of the treatment alternatives, and expectations with the patients. Cystoprostatectomy followed by immediate androgen deprivation therapy may be a feasible option for selected patients with previously untreated prostate cancer involving the bladder neck because of excellent local control and long term survival.

  16. What is the correct staging and treatment strategy for locally advanced prostate cancer extending to the bladder?

    Science.gov (United States)

    Yüksel, Özgür Haki; Verit, Ayhan; Ürkmez, Ahmet

    2015-06-01

    In locally advanced prostate cancer with bladder invasion, frequently encountered problems such as bleeding, urinary retention, hydronephrosis, and pain create distress for the patients. Therefore patients' quality of life is disrupted and duration of hospitalization is prolonged. Relevant literature about accurate staging and treatment of locally advanced prostate cancer with bladder invasion was investigated. Locally advanced prostate cancer can present as a large-volume aggressive tumor extending beyond boundaries of prostate gland, and involving neighboring structures which can be involved as recurrence(s) following initial local therapy. Survival times of these patients can range between 5 and 8 years. Their common characteristics are adverse and severe local symptoms unfavorably affecting quality of life Control of local symptoms and their effective palliation are independent clinical targets influencing survival outcomes of these patients. The treatment outcomes of locally advanced prostate cancer into the bladder are currently debatable. Although in the current TNM classification, it is defined in T4a, we think that this may be categorized as a subgroup of T3 and thus encourage surgeons for the indication of radical surgeries (radical prostatectomy, radical cystoprostatectomy) in selected patient populations after discussing issues concerning consequences of the treatment alternatives, and expectations with the patients. Cystoprostatectomy followed by immediate androgen deprivation therapy may be a feasible option for selected patients with previously untreated prostate cancer involving the bladder neck because of excellent local control and long term survival. PMID:26150029

  17. 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

  18. 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.

  19. Spectroscopic analysis of bladder cancer tissues using Fourier transform infrared spectroscopy

    Science.gov (United States)

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

    2012-03-01

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

  20. PET/CT in kidney and bladder cancer

    International Nuclear Information System (INIS)

    Full text: FDG PET/CT has traditionally been considered a method of limited use in tumors of the kidneys and excretory system. Major shortcoming of the method in kidney cancer is considered variable fixation and a more general lack of significant therapeutic alternatives that require early diagnosis of recurrence after nephrectomy. In the context of the modern methods of systemic anticancer therapy in kidney cancer, marking a significant success in terms of time to progression, the need of more detailed selection of the patients and the search methods for the early diagnosis and assessment of therapeutic response arises. While CT remains the primary method for the diagnosis of parenchymal metastases (lung, liver), the use of FDG PET/CT has a significant advantage in detecting of nodal metastasis, locoregional recurrence and bone metastasis. Interesting direction in the use of PET/CT remains the monitoring of therapeutic response to systemic therapy of metastatic kidney cancer. Unlike kidney cancer in transitional cell carcinoma of bladder (TCC), the application of FDG PET/CT is non- systematic and based on the specific clinical indications. As the main indicator can be observed the distant staging in locally advanced tumors and recurrences in restading after cystectomy. Besides the general advantages of PET/CT in terms of nodal and peritoneal involvement it should be noted that the role of the PET/CT in TCC is discussible. Application of FDG PET / CT in kidney cancer and TCC at this stage can not be considered as established, but while in TCCs, the method has sporadically application, mostly for specific clinical questions, the application in kidney cancer is significantly more systemic and in the context of systemic anti-tumor therapy allows early diagnosis and therapeutic approach modulation

  1. 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)

  2. 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.

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Cemal Selçuk İşoğlu

    2015-06-01

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

  6. 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

  7. 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

  8. [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

  9. 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; Zeuthen, J

    1990-01-01

    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......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...... the reduced ability of bladder cancer patient PBMC to develop LAK-cell cytotoxicity is a result of a low incidence of CD56+ and CD57+ cells in the blood. These findings indicate that IL-2 therapy alone might not be a sufficient therapy of bladder cancer patients....

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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...

  16. 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...

  17. Oncogenic activation of Pak1-dependent pathway of macropinocytosis determines BCG entry into bladder cancer cells

    OpenAIRE

    Redelman-Sidi, Gil; Iyer, Gopa; Solit, David; Glickman, Michael S.

    2013-01-01

    Bacille Calmette-Guerin (BCG) is an attenuated strain of Mycobacterium bovis that is used widely as a vaccine for tuberculosis and is used as an effective treatment for superficial bladder carcinoma. Despite being the most successful cancer biotherapy, its mechanism of action and response determinants remain obscure. Here we establish a model system to analyze BCG interaction with bladder cancer cells, using it to show that these cells vary dramatically in their susceptibility to BCG infectio...

  18. 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...

  19. Urinary high molecular weight matrix metalloproteinases as non-invasive biomarker for detection of bladder cancer

    OpenAIRE

    Mohammed, Mohammed A; Seleim, Manar F; Abdalla, Mohga S.; Sharada, Hayat M; Abdel Wahab, Abdel Hady A.

    2013-01-01

    Background Matrix Metalloproteinases (MMPs) are key molecules for tumor growth, invasion and metastasis. Over-expression of different MMPs in tumor tissues can disturb the homeostasis and increase the level of various body fluids. Many MMPs including high molecular weights (HMWs) were detected in the urine of prostate and bladder cancer patients. Our aim here is to assess the usefulness of HMW MMPs as non invasive biomarkers in bilharzial bladder cancer in Egyptian patients. Methods The activ...

  20. Intra-arterial chemotherapy in combination with radiotherapy for the treatment of patients with muscle-invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-04-01

    Authors reported results of three different therapies for bladder cancer. 1. Between September 1979 and March 1990, 45 patients with muscle-invasive bladder cancer were treated with intra-arterial doxorubicin (ADM) chemotherapy plus low-dose irradiation. ADM was administered intraarterially at a dose of 20 or 30 mg/body/day from day 1 to 3. Radiotherapy was given at a dose of 2 Gy/session concomitant with intra-arterial administration. Twenty-eight patients achieved complete response (CR) and in all of them, a functional bladder could be preserved. The median follow-up was 9.8 years. Of the 45 patients, 13 died of cancer, including 3 of the 28 with CR. The 10-year cause-specific survival rate of patients with CR was 90%. In contrast, the 10-year survival rate of 17 patients who did not achieve CR was 34%. 2. Authors have treated 21 patients who had locally advanced bladder cancer with this regimen. As an induction therapy, the intra-arterial chemotherapy consisted of 15 mg/m{sup 2}/day pirarubicin (THP) and 25 mg/m{sup 2}/day cisplatin (CDDP) plus 2 Gy of irradiation, which was given just before each chemotherapy session. As a maintenance treatment, patients were treated with THP once a month for 2 years. Among these patients, 19 achieved CR while 2 did not. One patient with CR had relapsed lung metastases 24 months after treatment and underwent thoracotomy. Only one patient who did not achieved CR died of cancer, while the remaining 19 patients show no evidence of disease and were able to preserve a functional bladder. 3. Nine patients were treated with glutathione and compared with 15 patients who were treated with the same regimen but without glutathione. The two groups did not differ regarding CR rate, however the incidence of neurotoxicity among patients receiving glutathione was significantly lower than that among patients who did not receive glutathione. (K.H.)

  1. Significance of Metabolic Super scan in Patients With Locally Advanced Bladder Cancer

    International Nuclear Information System (INIS)

    Non-metastatic metabolic related skeletal changes are predicted in patients with locally advanced bladder cancer. Renal impairment may be a contributing factor in such abnormalities. The aim of this study was to verify the presence of metabolic bone disease in patients with different pathological subgroups of locally advanced bladder cancer and determine its clinical impact, and to correlate these metabolic super scan features with variable laboratory tests of bone bio markers and renal functions. In this study, a total of 350 patients (mean age = 58±8.4 y) with histopathologically proven locally advanced bladder cancer; 238 transitional cell carcinoma (TCC), 100 squamous cell carcinoma (SCC), 7 adenocarcinoma, 2 mucinous adenocarcinoma, 2 undifferentiated carcinoma and 1 leiomyosarcoma. The patients were referred to the Nuclear Medicine Unit, National Cancer Institute, Cairo, Egypt, between July 2006 and December 2009. Whole body bone scan was obtained 3 hours following IV administration of 555-925 MBq Tc-99m MDP. Serum alkaline phosphatase (ALP), calcium and parathormone (PTH) levels were monitored as markers for bone metabolism while serum creatinine was used to monitor kidney function. The exclusion criteria included patients who had liver disease or those taking calcium or vitamin D supplement or any medication that affects bone metabolism. All bone scan results in the study were verified by correlation with other radiological imaging, laboratory data and follow-up for at least 12 months. According to bone scan results, patients were classified into four groups: group A: normal scan (n=223), group B: metabolic super scan features (MSS) (n=70), group C: metastatic bone disease (n=45) and group D: bone scan with indeterminate lesions (n=12). Osteomalacic MSS features were detected in 20 % of the studied patients (locally advanced bladder cancer) compared to 14.5% who had bone metastases. Contrary to metastases which showed high prevalence in TCC (P<0.001), MSS

  2. 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

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

    Science.gov (United States)

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

    2011-02-01

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

  4. Patient-recognition data-mining model for BCG-plus interferon immunotherapy bladder cancer treatment.

    Science.gov (United States)

    Shah, Shital C; Kusiak, Andrew; O'Donnell, Michael A

    2006-06-01

    Bladder cancer is the fifth most common malignant disease in the United States with an annual incidence of around 63,210 new cases and 13,180 deaths. The cost for providing care for patients with bladder cancer disease is high. Bladder cancer treatment options such as immunotherapy, chemotherapy, radiation therapy, transurethral resection, and cystectomy, are used with varying success rates. In this research, data from a nationwide bacillus Calmette-Gue rin (BCG) plus interferon-alpha (IFN-alpha) immunotherapy clinical trial was considered. Data mining algorithms were used to analyze the effectiveness of immunotherapy treatment and to understand the prominent parameters and their interactions. The extracted knowledge was used to build a patient recognition model for prediction of treatment outcomes. The data was analyzed to understand the impact of various parameters on the treatment outcome. A list of significant parameters such as cumulative tumor size, presence of residual disease, stages of prior bladder cancer, current state of bladder cancer, and the presence of current bladder cancer (T1) is provided. The decision-making approach outlined in the paper supplemented with additional knowledge bases will lead to a comprehensive analytical road map of the BCG/IFN-alpha immunotherapy treatment. It will provide individualized guidelines for each stage of the treatment as well as measure the success of the treatment. PMID:15978568

  5. 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

  6. 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.

  7. Evaluation of delivered dose for a clinical daily adaptive plan selection strategy for bladder cancer radiotherapy

    International Nuclear Information System (INIS)

    Purpose: To account for variable bladder size during bladder cancer radiotherapy, a daily plan selection strategy was implemented. The aim of this study was to calculate the actually delivered dose using an adaptive strategy, compared to a non-adaptive approach. Material and methods: Ten patients were treated to the bladder and lymph nodes with an adaptive full bladder strategy. Interpolated delineations of bladder and tumor on a full and empty bladder CT scan resulted in five PTVs for which VMAT plans were created. Daily cone beam CT (CBCT) scans were used for plan selection. Bowel, rectum and target volumes were delineated on these CBCTs, and delivered dose for these was calculated using both the adaptive plan, and a non-adaptive plan. Results: Target coverage for lymph nodes improved using an adaptive strategy. The full bladder strategy spared the healthy part of the bladder from a high dose. Average bowel cavity V30Gy and V40Gy significantly reduced with 60 and 69 ml, respectively (p < 0.01). Other parameters for bowel and rectum remained unchanged. Conclusions: Daily plan selection compared to a non-adaptive strategy yielded similar bladder coverage and improved coverage for lymph nodes, with a significant reduction in bowel cavity V30Gy and V40Gy only, while other sparing was limited

  8. The role of PD-L1 in the radiation response and clinical outcome for bladder cancer

    OpenAIRE

    Chun-Te Wu; Wen-Cheng Chen; Ying-Hsu Chang; Wei-Yu Lin; Miao-Fen Chen

    2016-01-01

    Identification of potential factors that can stratify a tumor’s response to specific therapies will aid in the selection of cancer therapy. The aim was to highlight the role of programmed cell death 1 ligand 1 (PD-L1) in bladder cancer. In this study, 92 of muscle-invasive bladder cancers and 28 of non- muscle invasive bladder cancers were selected for immunohistochemical staining analysis. Furthermore, human and murine bladder cancer cell lines were used to examine the correlation between PD...

  9. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  11. 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

  12. Synchronous bladder and prostate cancers in the specimens of radical cystoprostatectomy: a multicenter retrospective analysis.

    Science.gov (United States)

    Ozgür, Berat Cem; Köseoğlu, Ersin; Arık, Ali İhsan; Sarıcı, Haşmet; Bilgin, Ovünç; Yücetürk, Cem Nedim; Ozer, Elif; Güven, Eşref Oğuz; Telli, Onur; Atan, Ali; Eroğlu, Muzaffer

    2014-07-01

    The purpose of this study was to evaluate the features of prostate cancer that have been incidentally detected in radical cystoprostatectomy specimens of bladder cancer patients. The researchers of the current study retrospectively evaluated the data from 119 men who underwent radical cystoprostatectomy at four referral institutions in Ankara, Turkey. Of the 21 prostate cancer patients, 17 (81%) were aged ≥ 60 years; 10 (47.6%) had clinically significant diseases; three had a Gleason score of 6, three had a Gleason score of 7, three had a Gleason score of 8, one had a positive surgical margin along with extracapsular invasion of the tumor and a high Gleason score, and three patients had a tumor volume of ≥ 0.5 cm(3), of which two also had a high Gleason score. Patients were followed-up for a mean of 29 ± 10.2 months; the overall survival was 96.6% (n = 115) during that period. Preoperative digital rectal examination and prostate-specific antigen values did not differ between the benign and prostate cancer groups. There was no survival advantage in the insignificant prostate cancer and benign prostate groups. No additional benefit for predicting prostate cancer was found with digital rectal examination and prostate-specific antigen tests, although some clinicians advised such. In patients aged 60 years, the preoperative work-up may routinely include prostate biopsy, especially the apex. Preoperative findings of multifocality of bladder cancers and the presence of carcinoma in situ have the risk of prostatic involvement. PMID:24924843

  13. Genotoxicity of tobacco smoke-derived aromatic amines and bladder cancer: current state of knowledge and future research directions.

    Science.gov (United States)

    Besaratinia, Ahmad; Tommasi, Stella

    2013-06-01

    Bladder cancer is a significant public health problem, worldwide. In the United States, bladder cancer is the fourth most common cancer in men, and its recurrence rate is the highest among all malignancies. Tobacco smoking is the leading risk factor for bladder cancer. The risk of bladder cancer is directly related to the intensity and duration of smoking, while quitting smoking reduces this risk. The increased risk of smokers for developing bladder cancer is attributable to their exposure to aromatic amines, which constitute a family of known bladder carcinogens present in tobacco smoke. The underlying mechanism of action of aromatic amines in the genesis of bladder cancer is not, however, fully delineated. Research has identified a genotoxic mode of action, specifically DNA adduction and mutagenicity, for aromatic amines, which may account for their carcinogenicity. The present review summarizes our current knowledge on the DNA adduction and mutagenicity of aromatic amines in relation to smoking-associated bladder cancer. For illustrative purposes, representative results from published research on aromatic amine-induced DNA adduction and mutagenesis are discussed. The direction of future research on the underlying mechanisms of tobacco smoke-associated bladder carcinogenesis is also outlined. Understanding the molecular mechanisms of bladder carcinogenesis is essential for improving future strategies for prevention, early detection, treatment, and prognosis of this malignancy. PMID:23449930

  14. 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

  15. 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

    International Nuclear Information System (INIS)

    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

  16. 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.

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

    International Nuclear Information System (INIS)

    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.)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. Time-Trend in Epidemiological and Pathological Features of Schistosoma-Associated Bladder Cancer

    International Nuclear Information System (INIS)

    To investigate the different emerging trends in the features of bladder cancer along 17 years. Patients and Methods: During a 17-year period (1988- 2004), 5071 epithelial bladder cancer patients underwent radical cystectomy at the National Cancer Institute (NCI), Cairo University, Egypt. The time was divided into 3 time periods to detect changes of the clinico pathologic features of patients in these periods. Results: There was a significant progressive increase in the patients' age with time and decrease in squamous/ transitional ratio, with transient increase in male predominance during the 2nd time period. Moreover, there was a decrease in the well differentiated (grade 1) tumor (p<0.001) and an increase in the frequency of pelvic nodal involvement (p<0.001). Transitional cell carcinoma (TCC) patients were significantly older than those with squamous cell carcinoma (SCC) (p<0.001). Progressive increase of age with time was evident in TCC, SCC and adenocarcinoma patients. Male to female ratio changed significantly in TCC and SCC. Conclusion: Time trend was confirmed with relative decrease in frequency of SCC and increase of TCC with changes in their pathological details. The differences between their characteristics and that of the Western countries are decreasing.

  4. High risk bladder cancer: current management and survival

    Directory of Open Access Journals (Sweden)

    Anna M. Leliveld

    2011-04-01

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

  5. 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

  6. 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

  7. 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.

  8. Whole-genome sequencing of bladder cancers reveals somatic CDKN1A mutations and clinicopathological associations with mutation burden

    OpenAIRE

    Cazier, J.-B.; Rao, S. R.; Mclean, C. M.; A. L. Walker; Wright, B J; Jaeger, E. E. M.; Kartsonaki, C.; Marsden, L.; Yau, C; Camps, C.; Kaisaki, P.; ,; Allan, Christopher; Attar, Moustafa; Bell, John

    2014-01-01

    Bladder cancers are a leading cause of death from malignancy. Molecular markers might predict disease progression and behaviour more accurately than the available prognostic factors. Here we use whole-genome sequencing to identify somatic mutations and chromosomal changes in 14 bladder cancers of different grades and stages. As well as detecting the known bladder cancer driver mutations, we report the identification of recurrent protein-inactivating mutations in CDKN1A and FAT1. The former ar...

  9. 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.

  10. 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.

  11. Expression of Robo protein in bladder cancer tissues and its effect on the growth of cancer cells by blocking Robo protein

    OpenAIRE

    Li, Yang; Cheng, Hepeng; Xu, Weibo; Tian, Xin; Li, Xiaodong; Zhu, Chaoyang

    2015-01-01

    This study aimed to detect the expression of Slit signaling protein ligand Robo protein in human bladder cancer and para-carcinoma tissue, and observe the tumor cell survival and growth by inoculating the bladder cancer cells with the blocked signaling protein into the subcutaneous tissue of nude mice. The expression of Robo protein was detected in T24 cells in human bladder uroepithelium carcinoma and cultivated human bladder uroepithelium carcinoma confirmed by pathological diagnosis. The c...

  12. Endoscopic molecular imaging of human bladder cancer using a CD47 antibody.

    Science.gov (United States)

    Pan, Ying; Volkmer, Jens-Peter; Mach, Kathleen E; Rouse, Robert V; Liu, Jen-Jane; Sahoo, Debashis; Chang, Timothy C; Metzner, Thomas J; Kang, Lei; van de Rijn, Matt; Skinner, Eila C; Gambhir, Sanjiv S; Weissman, Irving L; Liao, Joseph C

    2014-10-29

    A combination of optical imaging technologies with cancer-specific molecular imaging agents is a potentially powerful strategy to improve cancer detection and enable image-guided surgery. Bladder cancer is primarily managed endoscopically by white light cystoscopy with suboptimal diagnostic accuracy. Emerging optical imaging technologies hold great potential for improved diagnostic accuracy but lack imaging agents for molecular specificity. Using fluorescently labeled CD47 antibody (anti-CD47) as molecular imaging agent, we demonstrated consistent identification of bladder cancer with clinical grade fluorescence imaging systems, confocal endomicroscopy, and blue light cystoscopy in fresh surgically removed human bladders. With blue light cystoscopy, the sensitivity and specificity for CD47-targeted imaging were 82.9 and 90.5%, respectively. We detected variants of bladder cancers, which are diagnostic challenges, including carcinoma in situ, residual carcinoma in tumor resection bed, recurrent carcinoma following prior intravesical immunotherapy with Bacillus Calmette-Guérin (BCG), and excluded cancer from benign but suspicious-appearing mucosa. CD47-targeted molecular imaging could improve diagnosis and resection thoroughness for bladder cancer. PMID:25355698

  13. 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

  14. 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

  15. 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.

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

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    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

  17. 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

  18. 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

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

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    Daniel Y.C. Heng

    2011-12-01

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

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

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    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

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

    Science.gov (United States)

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

    2015-08-01

    Biomarkers, such as microRNAs (miRNAs) may be useful for the diagnosis of bladder cancer. In order to understand the molecular mechanisms underlying bladder cancer, differentially expressed miRNAs (DE-miRNAs) and their target genes in bladder cancer were analyzed. In the present study, miRNA and mRNA expression profiles (GSE40355) were obtained from the Gene Expression Omnibus. These consisted of healthy bladder samples (n=8) and urothelial carcinoma samples (low-grade, n=8 and high-grade, n=8). DE-miRNAs and differentially expressed genes (DEGs) were identified using the limma package and the Benjamin and Hochberg method from the multtest package in R. Target genes of DE-miRNAs were screened. Associations between DEGs were investigated using STRING, and an interaction network was constructed using Cytoscape. Functional and pathway enrichment analyses were performed for DEGs from the interaction network. 87 DE-miRNAs and 2058 DEGs were screened from low-grade bladder cancer samples, and 40 DE-miRNAs and 2477 DEGs were screened from high-grade bladder cancer samples. DE-target genes were significantly associated with the regulation of cell apoptosis. Bladder cancer, non-small cell lung cancer and pancreatic cancer biological pathways were found to be enriched. The results of the present study demonstrated that E2F transcription factor 1, which is targeted by miR-106b, and cyclin-dependent kinase inhibitor 2A (CDKN2A) and V-Erb-B2 avian erythroblastic leukemia viral oncogene homolog-2, which are targeted by miR-125b, participate in the bladder cancer pathway. In conclusion, DE-miRNAs in bladder cancer tissue samples and DE-targeted genes, such as miR-106b and CDKN2A, which were identified in the present study, may provide the basis for targeted therapy for breast cancer and enhance understanding of its pathogenesis. PMID:25955758

  2. Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells

    International Nuclear Information System (INIS)

    The importance of various inflammatory cytokines in maintaining tumor cell growth and viability is well established. Increased expression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) has previously been associated with various types of adenocarcinoma. MIF IHC was used to localize MIF in human bladder tissue. ELISA and Western blot analysis determined the synthesis and secretion of MIF by human bladder transitional cell carcinoma cells. The effects of MIF inhibitors (high molecular weight hyaluronate (HA), anti-MIF antibody or MIF anti-sense) on cell growth and cytokine expression were analyzed. Human bladder cancer cells (HT-1376) secrete detectable amounts of MIF protein. Treatment with HA, anti-MIF antibody and MIF anti-sense reduced HT-1376 cell proliferation, MIF protein secretion, MIF gene expression and secreted inflammatory cytokines. Our evidence suggests MIF interacts with the invariant chain, CD74 and the major cell surface receptor for HA, CD44. This study is the first to report MIF expression in the human bladder and these findings support a role for MIF in tumor cell proliferation. Since MIF participates in the inflammatory response and bladder cancer is associated with chronic inflammatory conditions, these new findings suggest that neutralizing bladder tumor MIF may serve as a novel therapeutic treatment for bladder carcinoma

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

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    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.

  4. Experimental and clinical treatment of bladder cancer with 125I-iododeoxyuridine

    International Nuclear Information System (INIS)

    Radionuclide can cause auger effect through disintegration low-energy electron (125I-iododeoxyuridine (125I-UdR) is an efficient carrier inducting 125I to cell nucleolus, it is incorporated into DNA specificity only in S-phase cells. A series of studies show that 125I can absorb more likely to tumor cells, instead of the normal cell division, thus effectively splitting radiotherapy of malignant lesions. As bladder is a natural lumen, it has a unique easy perfusion and observational. 125I-UdR can kill effiently and selectively the cells of bladder turnout, reducing markedly the ratio of its recurrence of surgical treatment of patients with bladder cancer, so as to improve the survival rate. It can be used as a surgical adjuvant treatment method, is expected to be a safe, efficient and less adverse reaction the new therapies for bladder cancer treatment. (authors)

  5. TRAIL-induced apoptosis and expression of death receptor TRAIL-R1 and TRAIL-R2 in bladder cancer cells.

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    Zenon P Czuba

    2010-05-01

    Full Text Available Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L is a member of TNF superfamily able to induce programmed death in cancer cells with no toxicity against normal tissues. TRAIL mediate apoptosis follows binding to the two death receptors, TRAIL-R1 (DR4 and/or TRAIL-R2 (DR5. In this study we investigated the cytotoxic and apoptotic effect of TRAIL on bladder cancer cells and the expression of death receptor TRAIL-R1 and TRAIL-R2 on the surface of these cancer cells. Three human bladder transitional cancer cell (TCC lines - SW780, 647V and T24 were tested for TRAIL sensitivity. The bladder cancer cells were incubated with human soluble recombinant TRAIL. Cytotoxicity was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-dimethyltetrazolium bromide and LDH (lactate dyhydrogenase assays. Apoptosis was detected by flow cytometry with annexin V-FITC/propidium iodide and by fluorescence microscopy with Hoechst 33342/annexin V-FITC/Ethidium Homodimer. The cell surface expression of TRAIL death receptors on bladder cancer were determined using flow cytometry with phycoerythrin-conjugated monoclonal anti-human TRAIL-R1 and TRAIL-R2. Our investigations confirmed that SW780 cells were sensitive to TRAIL, and two other bladder cancer cell lines, 647V and T24, were resistant to TRAIL induced apoptosis. We therefore examined the expression of TRAIL death receptors on bladder cancer cell surfaces. We showed decreased expression of TRAIL-R2 receptor in TRAIL-resistant bladder cancer cells and increased expression of this death receptor in TRAIL-sensitive SW780 cells. The expression of TRAILR1 receptor was similar in all bladder cancer cell lines. TRAIL is one of the promising candidates for cancer therapeutics. However, some cancer cells are resistant to TRAIL-mediated apoptosis. It is therefore important to overcome this resistance for the clinical use of TRAIL in cancer therapy. TRAIL death receptors are attractive therapeutic targets in

  6. Possible disease remission in patient with invasive bladder cancer with D-fraction regimen

    OpenAIRE

    Konno, Sensuke

    2009-01-01

    Srinivas Rajamahanty, Brandon Louie, Cormac O’Neill, Muhammad Choudhury, Sensuke KonnoDepartment of Urology, New York Medical College, Valhalla, New York, USAAbstract: Superficial bladder tumors are the most prevalent form of bladder cancers and transurethral resection is the primary surgical modality for those tumors. However, nearly 65% of patients will have tumor recurrence in five years while about 15% will have progression to muscle invasion. Thus, the primary therapeutic aim i...

  7. 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

  8. 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

  9. Late effects on the urinary bladder in patients treated for cancer in childhood: a report from the Children's Oncology Group.

    Science.gov (United States)

    Ritchey, Michael; Ferrer, Fernando; Shearer, Patricia; Spunt, Sheri L

    2009-04-01

    Childhood cancer survivors who have had pelvic or central nervous system surgery or have received alkylator-containing chemotherapy or pelvic radiotherapy as part of their cancer therapy may experience urinary bladder late effects. This article reviews the medical literature on long-term bladder complications in survivors of childhood cancer and outlines the Children's Oncology Group Long-Term Follow-up (COG LTFU) Guidelines related to bladder function. An overview of the treatment of bladder late effects and recommended counseling for survivors with these complications are presented. PMID:18985721

  10. 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

  11. 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

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

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    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.

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

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    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.

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

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    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.

  15. Gecko proteins induce the apoptosis of bladder cancer 5637 cells by inhibiting Akt and activating the intrinsic caspase cascade.

    Science.gov (United States)

    Kim, Geun-Young; Park, Soon Yong; Jo, Ara; Kim, Mira; Leem, Sun-Hee; Jun, Woo-Jin; Shim, Sang In; Lee, Sang Chul; Chung, Jin Woong

    2015-09-01

    Gecko proteins have long been used as anti-tumor agents in oriental medicine, without any scientific background. Although anti-tumor effects of Gecko proteins on several cancers were recently reported, their effect on bladder cancer has not been investigated. Thus, we explored the anti-tumor effect of Gecko proteins and its cellular mechanisms in human bladder cancer 5637 cells. Gecko proteins significantly reduced the viability of 5637 cells without any cytotoxic effect on normal cells. These proteins increased the Annexin-V staining and the amount of condensed chromatin, demonstrating that the Gecko proteinsinduced cell death was caused by apoptosis. Gecko proteins suppressed Akt activation, and the overexpression of constitutively active form of myristoylated Akt prevented Gecko proteins-induced death of 5637 cells. Furthermore, Gecko proteins activated caspase 9 and caspase 3/7. Taken together, our data demonstrated that Gecko proteins suppressed the Akt pathway and activated the intrinsic caspase pathway, leading to the apoptosis of bladder cancer cells. [BMB Reports 2015; 48(9): 531-536]. PMID:26246284

  16. 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

  17. Experimental Treatment of Bladder Cancer with Bi-213-anti-EGFR MAb

    International Nuclear Information System (INIS)

    Therapy of non-muscle-invasive bladder cancer (carcinoma in situ) comprises transurethral resection of the tumour and subsequent instillation of the chemotherapeutic drug mitomycin C in order to eradicate remaining tumour cells. Yet 15 – 40% of treated patients relapse within 5 years. Therefore, new therapeutic strategies to combat tumour recurrence are needed. Alpha-particle emitting radionuclides efficiently kill single tumour cells or small tumour cell clusters. Because the epidermal growth factor receptor (EGFR) is overexpressed on bladder cancer cells, conjugates composed of the alpha-emitter Bi-213 and the anti-EGFR antibody matuzumab should provide a powerful drug to eliminate disseminated bladder cancer cells. Therefore, the aims of our study were (i) to analyse the cytotoxic effects of Bi-213-anti-EGFR radioimmunoconjugates at the cellular level, (ii) to evaluate therapeutic efficacy of intravesically applied Bi-213- anti-EGFR-Mab in a nude mouse model with intravesical human bladder cancer xenografts, (iii) to compare Bi- 213-anti-EGFR-Mab efficacy with chemotherapy using mitomycin C and (iv) to demonstrate that radioimmunotherapy is not toxic to cells of the bladder wall and of the kidneys

  18. 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

  19. 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

  20. 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

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

    Science.gov (United States)

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

    2016-01-01

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

  2. 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.

  3. Lack of decorin expression by human bladder cancer cells offers new tools in the therapy of urothelial malignancies.

    Directory of Open Access Journals (Sweden)

    Annele Sainio

    Full Text Available Decorin, a multifunctional small leucine-rich extracellular matrix proteoglycan, has been shown to possess potent antitumour activity. However, there is some uncertainty whether different cancer cells express decorin in addition to non-malignant stromal cells. In this study we clarified decorin expression by human bladder cancer cells both in vivo and in vitro. In addition, the effect of adenovirus-mediated decorin expression on human bladder cancer cells in vitro was examined. We first demonstrated using the publicly available GeneSapiens databank that decorin gene expression is present in both normal and malignant human bladder tissues. However, when we applied in situ hybridization with digoxigenin-labeled RNA probes for decorin on human bladder carcinoma tissue samples derived from a large radical cystectomy patient cohort (n = 199, we unambiguously demonstrated that invasive and non-invasive bladder carcinoma cells completely lack decorin mRNA. The cancer cells were also negative for decorin immunoreactivity. Instead, decorin expression was localized solely to original non-malignant stromal areas of bladder tissue. In accordance with the aforementioned results, human bladder cancer cells in vitro were also negative for decorin expression as shown by RT-qPCR analyses. The lack of decorin expression by bladder cancer cells was shown not to be due to the methylation of the proximal promoter region of the decorin gene. When bladder cancer cells were transfected with a decorin adenoviral vector, their proliferation was significantly decreased. In conclusion, we have shown that human bladder cancer cells are totally devoid of decorin expression. We have also shown that adenovirus-mediated decorin gene transduction of human bladder cancer cell lines markedly inhibits their proliferation. Thus, decorin gene delivery offers new potential therapeutic tools in urothelial malignancies.

  4. 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

  5. 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.

  6. 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

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

    International Nuclear Information System (INIS)

    Due to the possible side-effects of radical cystectomy for muscle-invading urinary bladder cancer (UBC), radiotherapy remains an attractive organ-sparing treatment option, either alone or combined with increasingly effective chemotherapy. Radiation dose escalation may further improve the results obtained with radiotherapy. This Ph.D. program aimed at developing improved conformal radiotherapy techniques required for dose escalation in bladder irradiation. Initially, computer-controlled movement of the collimators during beam delivery was applied to shape partially wedged beams (PWBs), designed to conform the dose distribution to bladder targets. The dosimetric verification and treatment planning implementation of PWBs were addressed. Particular attention was given to dynamic beam isodose verification with the BMS-96 diode array. The theoretical clinical impact of PWBs in bladder irradiation was evaluated in a planning study. Using PWBs the dose homogeneity inside bladder targets improved and normal tissue (small intestine and rectum) doses were reduced. Judged from normal tissue complication probability (NTCP) modeling, PWBs would allow radiation dose escalation with 2-6 Gy in up to 60% of the patients without increasing the estimated combined NTCP relative to the standard setup. This work also demonstrated the uncertainty in intestine and rectum tolerance data and the differences between the various NTCP models. Finally, the internal bladder motion and patient setup variation were quantified from weekly repeat CT scans and electronic portal images, and new bladder treatment margins were derived. Currently, a bladder dose escalation trial using the PWB principle is performed, testing if the whole bladder target dose can be increased from 64 to 68 Gy while maintaining a low level of treatment-induced complications

  8. Evaluation of Urinary Nuclear Matrix Protein-22 as Tumor Marker Versus Tissue Polypeptide Specific Antigen in Bilharzial and Bladder Cancer

    International Nuclear Information System (INIS)

    Urinary nuclear matrix protein-22 (NMP-22) and tissue polypeptide specific antigen (TPS) were determined as potential marker for early detection of bladder tumors in patients with high risk (Bilharzial-patients), monitoring and follow up bladder cancer patients. The objective was to determine sensitivity and specificity of markers for bilharzial and cancer lesions. The levels of two parameters were determined pre and post operation. A total of 110 individuals, 20 healthy, 20 bilharzial patients and 70 bladder cancer patients with confirmed diagnosis were investigated. Urine samples were assayed for NMP-22 and TPS test kits. Some bladder cancer patients were selected to follow up. NMP-22 showed highly significant increase (P,0.001) more than TPS (P<0.01) in bladder cancer patients when compared with bilharzial and control group. Overall sensitivity is 7.8% for TPS and 98.5% for NMP-22

  9. 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...

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

    International Nuclear Information System (INIS)

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

  11. Neoadjuvant or adjuvant chemotherapy: what is the best treatment of muscle invasive bladder cancer?

    Directory of Open Access Journals (Sweden)

    Nabil Ismaili

    2011-09-01

    Full Text Available Bladder cancer is the fourth most common cancer for men and the eighth most common cancer for women. Transitional cell carcinoma is the most predominant histological type. Bladder cancer is highly chemosensitive. In metastatic setting the treatment is based on cisplatin chemotherapy regimens type MVAC, MVAC-HD or gemcitabine plus cisplatin. The standard treatment of muscle invasive operable bladder cancer (T2–T4 used widely was radical cystectomy with pelvic lymph nodes dissection; the anatomical extent of pelvic lymphadenectomy has not accurately been defined so far. However, in the last decade, the treatment of tumors was improved by the introduction of chemotherapy as part of the management of the disease. Neoadjuvant chemotherapy should be considered at first, as standard treatment of choice, before local treatment for patients with good performance status (0–1 and good renal function–glomerular filtration rate (GFR >60 mL/min. For patients treated with primary surgery, adjuvant chemotherapy is a valuable option in the case of lymph nodes involvement. This brief review would provide the evidence of the role of neoadjuvant chemotherapy in the management of operable muscle invasive (T2–T4 bladder cancer.

  12. A Case of Metastatic Bladder Cancer in Both Lungs Treated with Korean Medicine Therapy Alone

    OpenAIRE

    Lee, Dong-Hyun; Kim, Sung-Su; Seong, Shin; Woo, Chang-Ryoul; Han, Jae-Bok

    2014-01-01

    Abstract This case report is aimed to investigate the effects of Korean medicine therapy (KMT) including oral herbal medicine and herb nebulizer therapy in treating metastatic bladder cancer in the lungs. A 74-year-old man was diagnosed with metastatic bladder cancer in both lungs in August 2013. He refused any chemotherapy and was admitted to our hospital in a much progressed state on January 11, 2014. Since then, he was treated with KMT until May 17, 2014. The main oral herbal medicines wer...

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

    OpenAIRE

    Li, Fei; An, Shengli; Hou, Lina; Chen, Pengliang; Lei, Chengyong; TAN, WANLONG

    2014-01-01

    Findings from epidemiologic studies concerning red and processed meat intake and bladder cancer risk remain conflicting. Thus, we conducted this meta-analysis to examine the associations of red and processed meat intake with bladder cancer. Eligible studies published up to May 2014 were retrieved via both computer searches and review of references. Finally, we identified 14 studies on red meat (involving 9,084 cases) and 11 studies on processed meat (7,562 cases) involving up to 1,558,848 ind...

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

    OpenAIRE

    Ayyathurai, Rajinikanth; Soloway, Mark S.

    2011-01-01

    Upper urinary tract (UUT) transitional cell carcinoma (TCC) is relatively rare tumor. Approximately 0.7-4% of patients with primary bladder cancer develops UUT-TCC. The symptoms related to an UUT-TCC often occur with an advanced stage which leads one to emphasize a surveillance strategy to monitor the UUT to allow for an earlier diagnosis. Although the risk of UUT-TCC after bladder cancer is well established, there is a paucity of recommendations suggesting the optimal method and frequency of...

  15. Overexpression of Bcl-2 enhances metastatic potential of human bladder cancer cells

    OpenAIRE

    Miyake, H; Hara, I.; Yamanaka, K.; Gohji, K.; Arakawa, S; Kamidono, S.

    1999-01-01

    We investigated the effect of Bcl-2 expression on the metastatic process of bladder cancer cells by using the Bcl-2-transfected human bladder cancer cell lines (KoTCC-1/BH) and the control vector only-transfected cell line (KoTCC-1/C), which were generated in our previous study (Miyake et al (1998) Oncogene 16: 933–934). When they were injected intravenously into athymic nude mice, KoTCC-1/BH formed more than three times as many tumour nodules in the lungs as did KoTCC-1/C. In addition, tumou...

  16. 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 ...

  17. 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...

  18. Licochalcone A induces T24 bladder cancer cell apoptosis by increasing intracellular calcium levels.

    Science.gov (United States)

    Yang, Xinhui; Jiang, Jiangtao; Yang, Xinyan; Han, Jichun; Zheng, Qiusheng

    2016-07-01

    Licochalcone A (LCA) has been reported to significantly inhibit cell proliferation, increase reactive oxygen species (ROS) levels, and induce apoptosis of T24 human bladder cancer cells via mitochondria and endoplasmic reticulum (ER) stress-triggered signaling pathways. Based on these findings, the present study aimed to investigate the mechanisms by which LCA induces apoptosis of T24 cells. Cultured T24 cells were treated with LCA, and cell viability was measured using the sulforhodamine B assay. Apoptosis was detected by flow cytometry with Annexin V/propidium iodide staining, and by fluorescent microscopy with Hoechst 33258 staining. The levels of intracellular free calcium ions were determined using Fluo-3 AM dye marker. Intracellular ROS levels were assessed using the 2',7'-dichlorodihydrofluorescein diacetate probe assay. The mitochondrial membrane potential was measured using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl benzimidazole carbocyanine iodide. Furthermore, the mRNA expression levels of B‑cell lymphoma (Bcl)‑extra large, Bcl‑2‑associated X protein, Bcl‑2‑interacting mediator of cell death, apoptotic protease activating factor‑1 (Apaf‑1), calpain 2, cysteinyl aspartate specific proteinase (caspase)‑3, caspase‑4 and caspase‑9 were determined using reverse transcription semiquantitative and quantitative polymerase chain reaction analyses. Treatment with LCA inhibited proliferation and induced apoptosis of T24 cells, and increased intracellular Ca2+ levels and ROS production. Furthermore, LCA induced mitochondrial dysfunction, decreased mitochondrial membrane potential, and increased the mRNA expression levels of Apaf‑1, caspase‑9 and caspase‑3. Exposure of T24 cells to LCA also triggered calpain 2 and caspase‑4 activation, resulting in apoptosis. These findings indicated that LCA increased intracellular Ca2+ levels, which may be associated with mitochondrial dysfunction. In addition, the ER stress pathway may be

  19. 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

  20. 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.

  1. Benign prostatic hyperplasia is a significant risk factor for bladder cancer in diabetic patients: a population-based cohort study using the National Health Insurance in Taiwan

    Directory of Open Access Journals (Sweden)

    Tseng Chin-Hsiao

    2013-01-01

    Full Text Available Abstract Background Diabetic patients have a higher risk of bladder cancer and benign prostatic hyperplasia (BPH. Theoretically, BPH patients may have an increased risk of bladder cancer because residual urine in the bladder surely increases the contact time between urinary excreted carcinogens and the urothelium. However, whether BPH increases bladder cancer risk in patients with type 2 diabetes has not been studied. Methods The reimbursement databases of all Taiwanese diabetic patients under oral anti-diabetic agents or insulin from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2006 and a total of 547584 men with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Incidences of bladder cancer for BPH by status and by duration were calculated and adjusted hazard ratios (95% confidence intervals were estimated by Cox regression. The effects of diabetes duration and medications used for diabetic control in relation with bladder cancer risk were also evaluated by Cox regression in BPH men. Results The incidences were 258.77 and 69.34 per 100,000 person-years for patients with and without BPH, respectively, adjusted hazard ratio 1.794 (1.572, 2.047. For BPH patients, those who underwent surgical procedures for BPH had a higher incidence than those who did not (355.45 vs. 250.09 per 100,000 person-years, respective adjusted hazard ratios: 2.459 (1.946, 3.109 and 1.709 (1.492, 1.958. The significantly higher risk could be demonstrated for BPH of any duration: respective adjusted hazard ratios 1.750 (1.430, 1.605, 1.844 (1.543, 2.203, 2.011 (1.680, 2.406 and 1.605 (1.341, 1.921 for BPH Conclusions BPH is a significant risk factor for bladder cancer in men with type 2 diabetes. Metformin may protect against bladder cancer in BPH men.

  2. 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

  3. 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

  4. Distinct pattern of p53 mutations in bladder cancer

    DEFF Research Database (Denmark)

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

    1993-01-01

    A distinct mutational spectrum for the p53 tumor suppressor gene in bladder carcinomas was established in patients with known exposures to cigarette smoke. Single-strand conformational polymorphism analysis of exons 5 through 8 of the p53 gene showed inactivating mutations in 16 of 40 (40%) bladder....... The results suggest that, although cigarette smoke exposure may not significantly alter the kinds of mutations sustained in the p53 gene, it may act to increase the extent of DNA damage per mutagenic event....

  5. Overall survival and local control following combined modality therapy and selective bladder preservation for invasive bladder cancer

    International Nuclear Information System (INIS)

    Purpose/Objective: Bladder preservation, in the interest of quality of life, is secondary to the primary treatment goal of curing the patient. To evaluate the long term efficacy of a selective bladder preserving approach we updated our prospective series which now includes 40 patients surviving and under surveillance for 5 or more years. Materials and Methods: From 1986 through 1993, 106 patients (median age 68 years) with muscle-invading tumor (stages T2-T4a, Nx, M0) initiated a protocol of maximal transurethral resection followed by 2 cycles of methotrexate, cisplatin and vinblastine plus cisplatin x2 with 40Gy pelvic irradiation. Complete responders and all non-cystectomy candidates received consolidation by cisplatin and 24.8Gy. Incomplete responders underwent immediate radical cystectomy as did those who developed recurrent invasive tumor. Median follow-up is 53 months. Results: Of all 106 patients who initiated induction Combined Modality Treatment (CMT): 1) 83 patients or 78% completed CMT; 33% developed moderate or severe leukopenia, 2) 74 patients (70%) had a Complete Response (CR), 3) the 5 year actuarial overall survival is 52%; for clinical stage T2 and T3-T4a this is 63% and 45%, respectively, 4) 36 patients (34%) have had cystectomy, all for tumor (6 because CMT wasn't tolerated, 13 for < CR, 17 for recurrence); no patient required cystectomy for complications; the 5 year survival with an intact functioning bladder is 43%, 5) 31 patients (20%) have had relapse of a superficial TCC with 4 requiring cystectomy after failing conservative management with a subsequent median follow-up of 58 months. Conclusion: These data demonstrate 1) that induction CMT with transurethral surgery and chemo-radiotherapy and selection for organ-conservation by response have a 52% overall survival which is comparable to immediate cystectomy-based prospective studies of patients with similar age and clinical stages and 2) that the majority of long term survivors retain fully

  6. Prognostic significance of clinico-pathological parameters in locally advanced bladder cancer

    International Nuclear Information System (INIS)

    Organ preservation should be the main interest in the treatment of patients with locally advanced bladder cancer. The selection of patients for the respective therapy is mainly based on tumor staging, grading and multiplicity. In the present study data from 65 patients with locally advanced bladder tumors treated by an integrated chemo- radio-therapy were evaluated. The cytostatic drugs used were either Cisplatinium (19 patients (29,2 %))or Adriamycin (21 patients (32.3 %)) alone or a combination (25 patients (38,4 %)). Complete remission was achieved in 53 patients (81,5 %). The following parameters were investigated and evaluated for their prognostic significance in a multivariant analysis. 1.) Histology: tumorgrade, tumortype-papillary/solid, infiltration patterns, lymph and/or blood vessel invasion and areas of squamous cell differentiation within the tumor; 2.) Clinic: staging, tumor volume, multiplicity, therapy and hydronephrosis. The predictive value of these parameters in regard to the therapy response of the tumors was calculated. This study actually showed a statistically worse outcome for patients with papillary histology. All other parameters did not show any significance concerning the tumor remission in response to integrated radio-chemo-therapy. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  8. Induction of Apoptosis by Costunolide in Bladder Cancer Cells is Mediated through ROS Generation and Mitochondrial Dysfunction

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    Ichiro Tsuji

    2013-01-01

    Full Text Available Despite the availability of several therapeutic options, a safer and more effective modality is urgently needed for treatment of bladder cancer. Costunolide, a member of sesquiterpene lactone family, possesses potent anticancer properties. In this study, for the first time we investigated the effects of costunolide on the cell viability and apoptosis in human bladder cancer T24 cells. Treatment of T24 cells with costunolide resulted in a dose-dependent inhibition of cell viability and induction of apoptosis which was associated with the generation of ROS and disruption of mitochondrial membrane potential (Δψm. These effects were significantly blocked when the cells were pretreated with N-acetyl- cysteine (NAC, a specific ROS inhibitor. Exposure of T24 cells to costunolide was also associated with increased expression of Bax, down-regulation of Bcl-2, survivin and significant activation of caspase-3, and its downstream target PARP. These findings provide the rationale for further in vivo and clinical investigation of costunolide against human bladder cancer.

  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.

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    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. Diabetes mellitus and risk of bladder cancer: a meta-analysis of cohort studies.

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    Xin Xu

    Full Text Available OBJECTIVE: Diabetes is associated with increased risk of cancer at several sites, but its association with risk of bladder cancer is still controversial. We examined this association by conducting a systematic review and meta-analysis of cohort studies. METHODS: Studies were identified by searching PubMed, EMBASE, Scopus, Web of Science, Cochrane register, and Chinese National Knowledge Infrastructure (CNKI databases through April 29, 2012. Summary relative risks (SRRs with their corresponding 95% confidence intervals (CIs were calculated using a random-effects model. RESULTS: A total of fifteen cohort studies were included in this meta-analysis. Analysis of all studies showed that diabetes was associated with a borderline statistically significant increased risk of bladder cancer (RR 1.11, 95% CI 1.00-1.23; p<0.001 for heterogeneity; I(2 = 84%. When restricting the analysis to studies that had adjusted for cigarette smoking (n = 6 or more than three confounders (n = 7, the RRs were 1.32 (95% CI 1.18-1.49 and 1.20 (95% CI 1.02-1.42, respectively. There was no significant publication bias (p = 0.62 for Egger's regression asymmetry test. CONCLUSIONS: Our findings support that diabetes was associated with an increased risk of bladder cancer. More future studies are warranted to get a better understanding of the association and to provide convincing evidence for clinical practice in bladder cancer prevention.

  12. 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.

  13. [Necessity of bladder extirpation performance in the treatment of severe complications of its cancer].

    Science.gov (United States)

    Stakhovs'kyĭ, E O; St'opushkin, S P; Vukalovych, P S; Voĭlenko, O A

    2006-07-01

    Impact of bladder extirpation on quality of life in the patients, suffering severe complications of bladder cancer, was studied and efficacy of the urine turn off was determined. Results of treatment of 52 patients with complicated course of the bladder cancer, to whom bladderectomy was performed for vital indications using various methods of the urine turn off, were analyzed. After performance of intrarectal turn off of the urine with formation urinal reservoir or ileo-neobladderplasty there was noted the lowest rate of ureterohydronephros occurrence. Comparative analysis on quality of life index in the patients there was revealed its trustful improvement in postoperative period. Overall, positive result of treatment was achieved in more than 90% of patients. PMID:17115600

  14. 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; Nielsen, Søren Kynde; LU, Fokdal; Paludan, Merete; Lindegaard, Jacob Christian; Tanderup, Kari

    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...

  15. Effect of Bladder Distension on Dose Distribution of Intracavitary Brachytherapy for Cervical Cancer: Three-Dimensional Computed Tomography Plan Evaluation

    International Nuclear Information System (INIS)

    Purpose: To quantify the effect of bladder volume on the dose distribution during intracavitary brachytherapy for cervical cancer. Methods and Patients: The study was performed on 10 women with cervical cancer who underwent brachytherapy treatment. After insertion of the brachytherapy applicator, the patients were transferred to the computed tomography unit. Two sets of computed tomography slices were taken, including the pelvis, one with an empty bladder and one after the bladder was filled with saline. The target and critical organs were delineated by the radiation oncologist and checked by the expert radiologist. The radiotherapy plan was run on the Plato planning system, version 14.1, to determine the dose distributions, dose-volume histograms, and maximal dose points. The doses and organ volumes were compared with the Wilcoxon signed ranks test on a personal computer using the Statistical Package for Social Sciences, version 11.0, statistical program. Results: No significant difference regarding the dose distribution and target volumes between an empty or full bladder was observed. Bladder fullness significantly affected the dose to the small intestine, rectum, and bladder. The median of maximal doses to the small intestine was significantly greater with an empty bladder (493 vs. 284 cGy). Although dosimetry revealed lower doses for larger volumes of bladder, the median maximal dose to the bladder was significantly greater with a full bladder (993 vs. 925 cGy). The rectal doses were also affected by bladder distension. The median maximal dose was significantly lower in the distended bladder (481vs. 628 cGy). Conclusions: Bladder fullness changed the dose distributions to the bladder, rectum, and small intestine. The clinical importance of these changes is not known and an increase in the use of three-dimensional brachytherapy planning will highlight the answer to this question

  16. Muscle invasive bladder cancer culminating with leptomeningeal carcinomatosis

    OpenAIRE

    Swallow, Tom W.; Mabbutt, Scott; Bell, Charles R.W.

    2015-01-01

    This case reports highlights a rare metastatic manifestation of transitional cell carcinoma of the bladder. The onset of symptoms associated with meningeal irritation should be investigated. However, there is little consensus in the treatment of leptomeningeal carcinomatosis and it should be considered a poor prognostic sign with symptomatic management.

  17. 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.

  18. 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.

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

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    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.

  20. Inhibition of growth, migration and invasion of human bladder cancer cells by antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, and its molecular mechanisms.

    Science.gov (United States)

    Chiu, Kun-Yuan; Wu, Chun-Chi; Chia, Chi-Hao; Hsu, Shih-Lan; Tzeng, Yew-Min

    2016-04-10

    Bladder cancer is the ninth most common cancer around the world, and is a severe urological cancer irrespective of sex. Approximately 65% of the bladder cancers will recur following surgery; with more than 20% of those patients showing an advanced and metastatic stage, with reducing prognosis. Metastasis causes the most death of bladder cancer yet current therapeutic options remain limited. Antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, has been identified as a strong cytotoxic agent against lung and metastatic breast cancer cells; however, the effects and mechanisms of antrocin on cancer growth and metastasis remain largely unclear. This study showed that treatment with cytotoxic concentration of antrocin induced both intrinsic and extrinsic apoptotic pathways in human bladder cancer 5637 cells, evidenced by increase of Fas, DR5, Bax expression and caspase-3, -8 and -9 activation. Exposure to non-cytotoxic concentrations of antrocin significantly inhibited cell growth, migration, and invasion, which was associated with decreased phosphorylation of focal adhesion kinase (FAK) and paxillin. Antrocin also reduced subcellular distribution of FAK and paxillin at the focal adhesion contacts of the cell periphery site, and disrupted the formation of filopodia and lamellipodia. Moreover, antrocin increased epithelial-to-mesenchymal transition-related gene E-cadherin and decreased vimentin expression. Real-time PCR analysis showed that antrocin downregulated the expression of mRNA of several MMPs, including MMP-2. Moreover, the phosphorylation of ERK and c-Fos were also attenuated by antrocin. Data from chromatin immunoprecipitation assay demonstrated that antrocin decreased the DNA binding activity of c-Fos to the upstream/enhancer region of MMP-2 promoter, an action likely to result in the reducing MMP-2 expression. Overall, this is the first study which demonstrates that antrocin-inhibited migration and invasion of bladder cancer cells is partly

  1. Inhibitory role of the small leucine-rich proteoglycan biglycan in bladder cancer.

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    Christian Niedworok

    Full Text Available BACKGROUND: Urothelial bladder cancer is the ninth most common cancer. Despite surgical and chemotherapeutic treatment the prognosis is still poor once bladder cancer progresses to a muscle-invasive state. Discovery of new diagnostic markers and pathophysiologic effectors might help to contribute to novel diagnostic and therapeutic options. The extracellular matrix microenvironment shaped by the extracellular matrix critically affects tumor cell and stroma cell functions. Therefore, aim of the present study was to assess the possible implication of the small leucine-rich proteoglycan biglycan in progression of human urothelial bladder cancer. METHODS AND RESULTS: For this purpose tumor biopsies of 76 bladder cancer patients with different tumor stages (pTa, pT1-T4 were investigated with respect to biglycan expression and correlated with a long-term (10 years clinical follow-up. Interestingly, higher biglycan mRNA expression was associated with higher tumor stages and muscle invasiveness. In vitro knock-down of endogenous biglycan in human urothelial carcinoma cells (J82 cells increased proliferation, whereas addition of recombinant biglycan and overexpression of biglycan inhibited tumor cell proliferation. In line with this growth-inhibitory effect of biglycan, transplantation of J82 cells after knock-down of biglycan resulted in significantly increased growth of subcutaneous xenograft tumors in nude mice in vivo. Furthermore, treatment with two anti-proliferative, multi-receptor tyrosine kinase inhibitors-sunitinib and sorafenib-strongly upregulated biglycan expression. Collectively, the experimental data suggest that high biglycan expression is associated with reduced tumor cell proliferation. In accordance, Kaplan-Meier analysis revealed higher 10-year survival in patients with high biglycan mRNA expression in tumor biopsies. CONCLUSION: In conclusion, the present data suggest that biglycan is an endogenous inhibitor of bladder cancer cell

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

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    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.

  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. An adaptive radiotherapy planning strategy for bladder cancer using deformation vector fields

    International Nuclear Information System (INIS)

    Purpose: Adaptive radiotherapy (ART) has considerable potential in treatment of bladder cancer due to large inter-fractional changes in shape and size of the target. The aim of this study was to compare our clinically applied method for plan library creation that involves manual bladder delineations (Clin-ART) with a method using the deformation vector fields (DVFs) resulting from intensity-based deformable image registrations (DVF-based ART). Materials and methods: The study included thirteen patients with urinary bladder cancer who had daily cone beam CTs (CBCTs) acquired for set-up. In both ART strategies investigated, three plan selection volumes were generated using the CBCTs from the first four fractions; in Clin-ART boolean combinations of delineated bladders were used, while the DVF-based strategy applied combinations of the mean and standard deviation of patient-specific DVFs. The volume ratios (VRs) of the course-averaged PTV for the two ART strategies relative the non-adaptive PTV were calculated. Results: Both Clin-ART and DVF-based ART considerably reduced the course-averaged PTV, compared to non-adaptive RT. The VR for DVF-based ART was lower than for Clin-ART (0.65 vs. 0.73; p < 0.01). Conclusions: DVF-based ART for bladder irradiation has a considerable normal tissue sparing potential surpassing our already highly conformal clinically applied ART strategy

  5. Adaptive plan selection vs. re-optimisation in radiotherapy for bladder cancer: A dose accumulation comparison

    International Nuclear Information System (INIS)

    Purpose: Patients with urinary bladder cancer are obvious candidates for adaptive radiotherapy (ART) due to large inter-fractional variation in bladder volumes. In this study we have compared the normal tissue sparing potential of two ART strategies: daily plan selection (PlanSelect) and daily plan re-optimisation (ReOpt). Materials and methods: Seven patients with bladder cancer were included in the study. For the PlanSelect strategy, a patient-specific library of three plans was generated, and the most suitable plan based on the pre-treatment cone beam CT (CBCT) was selected. For the daily ReOpt strategy, plans were re-optimised based on the CBCT from each daily fraction. Bladder contours were propagated to the CBCT scan using deformable image registration (DIR). Accumulated dose distributions for the ART strategies as well as the non-adaptive RT were calculated. Results: A considerable sparing of normal tissue was achieved with both ART approaches, with ReOpt being the superior technique. Compared to non-adaptive RT, the volume receiving more than 57 Gy (corresponding to 95% of the prescribed dose) was reduced to 66% (range 48–100%) for PlanSelect and to 41% (range 33–50%) for ReOpt. Conclusion: This study demonstrated a considerable normal tissue sparing potential of ART for bladder irradiation, with clearly superior results by daily adaptive re-optimisation

  6. 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

  7. 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.

  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. 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.

  10. 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.

  11. 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.

  12. 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....

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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....

  18. 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

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

    Science.gov (United States)

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

    2015-05-01

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

  1. Local immunotherapy based on agonistic CD40 antibodies effectively inhibits experimental bladder cancer

    OpenAIRE

    Sandin, Linda C; Tötterman, Thomas H; Sara M. Mangsbo

    2014-01-01

    Local immunotherapy resurfaces in the field of cancer as a potential way to cure localized and metastatic disease with limited toxic effects. We have recently demonstrated that local administration of agonistic CD40 antibodies can cure localized as well as disseminated bladder neoplasms. This approach reduces the circulating concentrations of antibodies that would result from systemic delivery, hence resulting in limited toxicity.

  2. Radiation therapy and cis-diammine-dichloroplatinum (II) in transplantable and primary murine bladder cancer

    International Nuclear Information System (INIS)

    Preoperative radiation improves survival in advanced bladder cancer but the high failure rate, primarily due to distant metastases, suggests a need for adjuvant chemotherapy. The optimal drug might exhibit an additive effect with radiotherapy. Transitional cell carcinoma (TCC) induced in mice by FANFT closely resembles the human counterpart, and both primary and transplanted tumors were used to evaluate the possible additive effect of cis DDP and cyclophosphamide (CY), two drugs with activity in TCC, with radiation. One hundred C3H/He mice had 5 x 104 TCC cells placed in their right hind limbs and randomized into a control (20) and 8 treatment groups (10); 3600 rad, 3600 rad + CY, 3600 rad + cis DDP, 1500 rad + cis DDP, 1500 rad + CY, CY, and cis DDP. Chemotherapy was initiated on day 7 and continued every week x 3. Radiation, in 250 rad or 600 rad fractions, was given biweekly to the tumor bearing limb using a CO60 source. 3600 rad alone produced 60% cures with a significant reduction in average tumor diameter (p < 0.001). 3600 rad + cis DDP achieved 78% cures, the best regimen. Therapy of palpable tumors yielded similar results--ave. tumor diameter (D-38) for controls 16.5, 3000 rad--10.6 (p < 0.001), cis DDP--10.2, CY + 1600 rad--8.1, cis DDP + 300 rad--6.2. Cis DDP + 3000 rad was significantly better than cis DDP or 3000 rad alone. One hundred fifty mice ingesting FANFT for 11 months were randomized into 7 groups and subjected to the same regimens to evaluate the effect on primary tumors. The greatest reduction in tumor volume was in mice receiving 1500 rad + cis DDP (mean bladder weight, 29.68 vs. controls 53.57, p < 0.005). These results consistently suggest cooperation between irradiation and cis DDP. Adjuvant cis DDP for invasive bladder cancer might be maximized by initiation with preoperative radiotherapy. Our initial clinical data with cis DDP + irradiation in advanced TCC are encouraging

  3. Antiangiogenesis as the novel mechanism for justicidin A in the anticancer effect on human bladder cancer.

    Science.gov (United States)

    Wang, Yi-Wen; Chuang, Jing-Jing; Chang, Tsuey-Yu; Won, Shen-Jeu; Tsai, Hung-Wen; Lee, Chung-Ta; Cheng, Hong-Lin; Tzai, Tzong-Shin; Liu, Hsiao-Sheng; Chow, Nan-Haw

    2015-04-01

    Justicidin A (JA) is one of the methanol extracts of Justicia procumbens and was reported to induce apoptosis and inhibit the proliferation of human colon cancer cells. Using bladder cancer as a paradigm, this study was designed to identify the novel molecular basis underlying the antiangiogenic activities of JA and its potential in cancer therapy. Human bladder cancer cell lines (TSGH8301 and RT4) and immortalized uroepithelial cell lines (E6 and E7) were chosen to investigate the efficacy of JA in cell proliferation, apoptosis, and angiogenesis in vitro. The biological effects of JA treatment in vivo were examined using a xenograft tumor model in SCID mice. JA showed a dose-dependent and time-dependent inhibition of cell proliferation on TSGH8301 cancer cells, with IC50 values determined to be 0.44 μmol/l. Of interest, TSGH8301 cancer cells were more sensitive to JA than E7 immortalized uroepithelial cells, especially at lower concentrations. We further showed that JA inhibited the autocrine production of angiogenic factors and matrix-degrading enzymes in vitro and microvessel density in SCID mice in vivo (P< 0.01). Both differential cytotoxicity and angiogenesis inhibition of JA were confirmed by SCID mice experiments. Together, JA showed antiangiogenesis in vitro and in vivo through pleiotropic positive and negative regulators of angiogenesis molecules. The current investigation supports the potential of JA as an alternative chemoprevention agent for human bladder cancer. PMID:25569706

  4. 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...

  5. Optimal control on bladder cancer growth model with BCG immunotherapy and chemotherapy

    Science.gov (United States)

    Dewi, C.; Trisilowati

    2015-03-01

    In this paper, an optimal control model of the growth of bladder cancer with BCG (Basil Calmate Guerin) immunotherapy and chemotherapy is discussed. The purpose of this optimal control is to determine the number of BCG vaccine and drug should be given during treatment such that the growth of bladder cancer cells can be suppressed. Optimal control is obtained by applying Pontryagin principle. Furthermore, the optimal control problem is solved numerically using Forward-Backward Sweep method. Numerical simulations show the effectiveness of the vaccine and drug in controlling the growth of cancer cells. Hence, it can reduce the number of cancer cells that is not infected with BCG as well as minimize the cost of the treatment.

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

    OpenAIRE

    Wei Meng; Alexander Huebner; Ahmad Shabsigh; Arnab Chakravarti; Tim Lautenschlaeger

    2012-01-01

    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 adja...

  8. Lack of Decorin Expression by Human Bladder Cancer Cells Offers New Tools in the Therapy of Urothelial Malignancies

    OpenAIRE

    Sainio, Annele; Nyman, Marie; Lund, Riikka; Vuorikoski, Sanna; Boström, Pia; Laato, Matti; Boström, Peter J.; Järveläinen, Hannu

    2013-01-01

    Decorin, a multifunctional small leucine-rich extracellular matrix proteoglycan, has been shown to possess potent antitumour activity. However, there is some uncertainty whether different cancer cells express decorin in addition to non-malignant stromal cells. In this study we clarified decorin expression by human bladder cancer cells both in vivo and in vitro. In addition, the effect of adenovirus-mediated decorin expression on human bladder cancer cells in vitro was examined. We first demon...

  9. Gecko proteins induce the apoptosis of bladder cancer 5637 cells by inhibiting Akt and activating the intrinsic caspase cascade

    OpenAIRE

    Kim, Geun-Young; Park, Soon Yong; Jo, Ara; Kim, Mira; Leem, Sun-Hee; Jun, Woo-Jin; Shim, Sang In; Lee, Sang Chul; Chung, Jin Woong

    2015-01-01

    Gecko proteins have long been used as anti-tumor agents in oriental medicine, without any scientific background. Although anti-tumor effects of Gecko proteins on several cancers were recently reported, their effect on bladder cancer has not been investigated. Thus, we explored the anti-tumor effect of Gecko proteins and its cellular mechanisms in human bladder cancer 5637 cells. Gecko proteins significantly reduced the viability of 5637 cells without any cytotoxic effect on normal cells. Thes...

  10. 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...

  11. 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...

  12. 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

  13. 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

  14. p16INK4a and p14ARF methylation as a potential biomarker for human bladder cancer.

    Science.gov (United States)

    Kawamoto, Ken; Enokida, Hideki; Gotanda, Takenari; Kubo, Hiroyuki; Nishiyama, Kenryu; Kawahara, Motoshi; Nakagawa, Masayuki

    2006-01-20

    Promoter hypermethylation is one of the putative mechanisms underlying the inactivation of negative cell-cycle regulators. We examined whether the methylation status of p16(INK4a) and p14(ARF), genes located upstream of the RB and p53 pathway, is a useful biomarker for the staging, clinical outcome, and prognosis of human bladder cancer. Using methylation-specific PCR (MSP), we examined the methylation status of p16(INK4a) and p14(ARF) in 64 samples from 45 bladder cancer patients (34 males, 11 females). In 19 patients with recurrent bladder cancer, we examined paired tissue samples from their primary and recurrent tumors. The methylation status of representative samples was confirmed by bisulfite DNA sequencing analysis. The median follow-up duration was 34.3 months (range 27.0-100.1 months). The methylation rate for p16(INK4a) and p14(ARF) was 17.8% and 31.1%, respectively, in the 45 patients. The incidence of p16(INKa) and p14(ARF) methylation was significantly higher in patients with invasive (>or=pT2) than superficial bladder cancer (pT1) (p=0.006 and p=0.001, respectively). No MSP bands for p16(INK4a) and p14(ARF) were detected in the 8 patients with superficial, non-recurrent tumors. In 19 patients with tumor recurrence, the p16(INK4a) and p14(ARF) methylation status of the primary and recurrent tumors was similar. Of the 22 patients who had undergone cystectomy, 8 (36.4%) manifested p16(INKa) methylation; p16(INK4a) was not methylated in 23 patients without cystectomy (p=0.002). Kaplan-Meier analysis revealed that patients with p14(ARF) methylation had a significantly poorer prognosis than those without (p=0.029). This is the first study indicating that MSP analysis of p16(INK4a) and p14(ARF) genes is a useful biomarker for the pathological stage, clinical outcome, and prognosis of patients with bladder cancer. PMID:16316628

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

    OpenAIRE

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

    2015-01-01

    Purpose: The aim of this study was to investigate occupational risk factors associated with bladder cancer. Materials and Methods: In this case–control study, control group included patients who referred to a specialized clinic in the same city and hospitals where patients had been registered. Data were entered into SPSS software. Odds ratios (OR) were calculated for occupational variables and other characteristics. Then, using logistic regression, the association between cancer and drugs was...

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

    OpenAIRE

    Ismaili Nabil

    2011-01-01

    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 o...

  17. 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...

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

    International Nuclear Information System (INIS)

    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 cyst