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Sample records for nonmuscle invasive bladder

  1. Nonmuscle invasive bladder cancer:a primer on immunotherapy

    Institute of Scientific and Technical Information of China (English)

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

    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.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Introduction: There have been no randomized controlled trials (RCTs) evaluating the clinical or economic benefit of mitomycin C intravesical therapy vs. radical cystectomy in patients with high-risk non-muscle invasive bladder cancer (NMIBC). We used the Archimedes computational model to simulate...

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  4. Natural biology and management of nonmuscle invasive bladder cancer

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jeffrey J Tomaszewski

    2010-05-01

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

  6. Defining and treating the spectrum of intermediate risk nonmuscle invasive bladder cancer

    NARCIS (Netherlands)

    Kamat, A.M.; Witjes, J.A.; Brausi, M.; Soloway, M.; Lamm, D.; Persad, R.; Buckley, R.; Bohle, A.; Colombel, M.; Palou, J.

    2014-01-01

    PURPOSE: Low, intermediate and high risk categories have been defined to help guide the treatment of patients with nonmuscle invasive bladder cancer (Ta, T1, CIS). However, while low and high risk disease has been well classified, the intermediate risk category has traditionally comprised a heteroge

  7. 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

  8. Proteomic analysis of urinary biomarker candidates for nonmuscle invasive bladder cancer.

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    Lindén, Mårten; Lind, Sara Bergström; Mayrhofer, Corina; Segersten, Ulrika; Wester, Kenneth; Lyutvinskiy, Yaroslav; Zubarev, Roman; Malmström, Per-Uno; Pettersson, Ulf

    2012-01-01

    Nonmuscle invasive tumors of the bladder often recur and thereby bladder cancer patients need regular re-examinations which are invasive, unpleasant, and expensive. A noninvasive and less expensive method, e.g. a urine dipstick test, for monitoring recurrence would thus be advantageous. In this study, the complementary techniques mass spectrometry (MS) and Western blotting (WB)/dot blot (DB) were used to screen the urine samples from bladder cancer patients. High resolving MS was used to analyze and quantify the urinary proteome and 29 proteins had a significantly higher abundance (pblot for four selected proteins; fibrinogen β chain precursor, apolipoprotein E, α-1-antitrypsin, and leucine-rich α-2-glycoprotein 1. Dot blot analysis of an independent urine sample set pointed out fibrinogen β chain and α-1-antitrypsin as most interesting biomarkers having sensitivity and specificity values in the range of 66-85%. Exploring the Human Protein Atlas (HPA) also revealed that bladder cancer tumors are the likely source of these proteins. They have the potential of being useful in diagnosis, monitoring of recurrence and thus may improve the treatment of bladder tumors, especially nonmuscle invasive tumors.

  9. Optimal Treatment for Intermediate- and High-Risk, Nonmuscle-Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    A.P.M. van der Meijden

    2006-01-01

    Full Text Available According to clinical and pathological factors the prognosis of a patient with non-muscle invasive bladder tumors can be assessed. The prognosis is determined by the likelihood of recurrence(30-70% and/or progression to muscle invasive bladder cancer(1-15%.Trans urethral resection of bladder tumors remains the initial therapy but adjuvant intravesical instillations are necessary.All patients benefit from a single immediate post operative instillation with a chemotherapeutic agent and for low risk tumors this is the optimal therapy.Patients with intermediate and high risk tumors need more intravesical chemo-or immunotherapy. Chemotherapy reduces recurrences but not progression. Intravesical immunotherapy(BCG prevents or delays progression. Patients at high risk for progression may need upfront cystectomy.

  10. Non-muscle invasive bladder cancer risk stratification

    Directory of Open Access Journals (Sweden)

    Sumit Isharwal

    2015-01-01

    Conclusion: EORTC and CUETO risk tables are the two best-established models to predict recurrence and progression in patients with NMIBC though they tend to overestimate risk and have poor discrimination for prognostic outcomes in external validation. Future research should focus on enhancing the predictive accuracy of risk assessment tools by incorporating additional prognostic factors such as depth of lamina propria invasion and molecular biomarkers after rigorous validation in multi-institutional cohorts.

  11. Fluorescence cystoscopy in patients with non-muscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    I. G. Rusakov

    2015-01-01

    Full Text Available The main challenge of treating non-muscle invasive bladder cancer is multifocal tumors. Current methods of diagnosis are failed to detect all superficial flat tumor lesions in bladder mucosa. The use of fluorescence imaging with 5-aminolevulinic acid (5-ALA allows to improve the sensibility of routine cystoscopy, but low specificity decreases its diagnostic accuracy. The method of fluorescence imaging combined with local fluorescence spectroscopy developed in P.A. Herzen MCRI has been shown to increase the specificity from 71% to 84%. Thus, local fluorescence spectroscopy in visible fluorescence of 5-ALA-induced protoporphyrin allows to perform guided biopsy and decrease the rate of diagnostic mistakes. 

  12. Quality-of-life survey for patients diagnosed with nonmuscle-invasive bladder cancer.

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    Abáigar-Pedraza, I; Megías-Garrigós, J; Sánchez-Payá, J

    2016-05-01

    To determine the reliability and validity of a quality-of-life survey for patients with nonmuscle-invasive bladder cancer. A total of 180 patients were included in the study. We developed a survey with 21 questions grouped into 5 areas. The patients filled in this survey and the Functional Assessment of Cancer Therapy - Bladder Cancer (FACT-BL) survey. To assess reliability, we calculated Cronbach's alpha coefficient and the kappa index. To determine criterion validity, we studied the association between the scores obtained from our survey and those from the FACT-BL survey using the Pearson correlation coefficient. To determine the construct validity (factorial and discriminatory), we performed a factor analysis, comparing it with Student's t-test for the scores obtained according to the tumour characteristics of reduced quality of life (e.g., malignancies located at the trigone of the bladder). Cronbach's alpha reliability coefficient was .83, and the kappa index varied between .7 and 1. For the association study between the new survey and the FACT-BL survey, we measured an r=.82 for the overall score and between r=.68 (disease) and r=.97 (sex life) in the various measures. In the factor analysis, we measured a Kaiser-Meyer-Olkin index of .77 and performed the Barlett test (P<.001). The comparison between the scores, in the presence or absence of certain tumour characteristics, has shown a reduced quality of life when those characteristics are present, which was statistically significant (P<.05) in the majority of cases. Our survey to measure the quality of life of patients with nonmuscle-invasive bladder cancer is reliable and valid. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Chromosomal imbalance in the progression of high-risk non-muscle invasive bladder cancer

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    Ørntoft Torben

    2009-05-01

    Full Text Available Abstract Background Non-muscle invasive bladder neoplasms with invasion of the lamina propria (stage T1 or high grade of dysplasia are at "high risk" of progression to life-threatening cancer. However, the individual course is difficult to predict. Chromosomal instability (CI is associated with high tumor stage and grade, and possibly with the risk of progression. Methods To investigate the relationship between CI and subsequent disease progression, we performed a case-control-study of 125 patients with "high-risk" non-muscle invasive bladder neoplasms, 67 with later disease progression, and 58 with no progression. Selection criteria were conservative (non-radical resections and full prospective clinical follow-up (> 5 years. We investigated primary lesions in 59, and recurrent lesions in 66 cases. We used Affymetrix GeneChip® Mapping 10 K and 50 K SNP microarrays to evaluate genome wide chromosomal imbalance (loss-of-heterozygosity and DNA copy number changes in 48 representative tumors. DNA copy number changes of 15 key instability regions were further investigated using QPCR in 101 tumors (including 25 tumors also analysed on 50 K SNP microarrays. Results Chromosomal instability did not predict any higher risk of subsequent progression. Stage T1 and high-grade tumors had generally more unstable genomes than tumors of lower stage and grade (mostly non-primary tumors following a "high-risk" tumor. However, about 25% of the "high-risk" tumors had very few alterations. This was independent of subsequent progression. Recurrent lesions represent underlying field disease. A separate analysis of these lesions did neither reflect any difference in the risk of progression. Of specific chromosomal alterations, a possible association between loss of chromosome 8p11 and the risk of progression was found. However, the predictive value was limited by the heterogeneity of the changes. Conclusion Chromosomal instability (CI was associated with "high risk

  14. Nonmuscle-invasive bladder cancer: what's changing and what has changed.

    Science.gov (United States)

    Manikandan, Ramanitharan; Rodriguez, Oscar; Parada, Rubén; Palou Redorta, Joan

    2017-02-03

    Nonmuscle-invasive bladder cancer (NMIBC) is a challenging disease to manage primarily due to its varied clinical course. The management of NMIBC has witnessed a widespread change with respect to its diagnosis and treatment. Although transurethral resection (TUR) and adjuvant bacillus Calmette-Guerin (BCG) stills remain the cornerstone, newer protocols has come into vogue to achieve optimal care. On the basis of a literature review, we aimed to establish 'what changes has already occurred and what is expected in the future' in NMIBC. A Medline search was performed to identify the published literature with respect to diagnosis, treatment and future perspectives on NMIBC. Particular emphasis was directed to determinants such as the quality of TUR and the newer modifications, Re-TUR, current status of newer macroscopic and microscopic imaging, role of urinary biomarkers, clinical, histologic and molecular predictors of high-risk disease, administration of intravesical agents, salvage therapy in BCG recurrence and the current best practice guidelines were analyzed. Optimal TUR, restaging in select group, incorporation of newer endoscopic imaging and judicious administration of intravesical chemo-immunotherapeutic agents can contribute to better patient care. Although there is a plethora of urinary markers, there is insufficient evidence for their use in isolation. The future probably lies in identification of genetic markers to determine disease recurrence, nonresponders to standard treatment and early institution of alternative/targeted therapy.

  15. Comparison of Guidelines on Non-Muscle Invasive Bladder Cancer (EAU, CUA, AUA, NCCN, NICE).

    Science.gov (United States)

    Power, Nicholas E; Izawa, Jonathan

    2016-01-07

    Non-muscle invasive bladder cancer (NMIBC) represents a considerably diverse patient group and the management of this complex disease is debatable. A number of panels from Europe and North America have convened on the topic and recently released guideline documents. The purpose was to compare and contrast the NMIBC guideline recommendations from the EAU (Europe), CUA (Canada), NCCN (United States), AUA (United States), and NICE (United Kingdom). All unabridged guideline documents were reviewed by the authors and comparisons were completed according to major topics in NMIBC. Despite a paucity of high level evidence regarding the majority of management topics in NMIBC, there was general agreement among the various guideline panels. Differences mainly centered on the categories of evidence synthesized and grades of recommendations. Each document offers a unique presentation of the available literature and guideline recommendation. The guidelines for NMIBC from the EAU, CUA, AUA, NCCN, and NICE provide considerable consensus regarding the management of this often difficult disease. Clinicians are encouraged to familiarize themselves with all of the guidelines in order to determine which style of presentation would be most useful to their current practice.

  16. The role of urine markers, white light cystoscopy and fluorescence cystoscopy in recurrence, progression and follow-up of non-muscle invasive bladder cancer

    NARCIS (Netherlands)

    Karaoglu, I.; Heijden, A.G. van der; Witjes, J.A.

    2014-01-01

    Non-muscle invasive bladder cancer (NMIBC) accounts for approximately 70 % of all bladder cancer cases and represents a heterogeneous pathological entity, characterized by a variable natural history and oncological outcome. The combination of cystoscopy and urine cytology is considered the gold stan

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

    NARCIS (Netherlands)

    Lerner, S.P.; Bajorin, D.F.; Dinney, C.P.; Efstathiou, J.A.; Groshen, S.; Hahn, N.M.; Hansel, D.; Kwiatkowski, D.; O'Donnell, M.; Rosenberg, J.; Svatek, R.; Abrams, J.S.; Al-Ahmadie, H.; Apolo, A.B.; Bellmunt, J.; Callahan, M.; Cha, E.K.; Drake, C.; Jarow, J.; Kamat, A.; Kim, W.; Knowles, M.; Mann, B.; Marchionni, L.; McConkey, D.; McShane, L.; Ramirez, N.; Sharabi, A.; Sharpe, A.H.; Solit, D.; Tangen, C.M.; Amiri, A.T.; Allen, E. Van; West, P.J.; Witjes, J.A.; Quale, D.Z.

    2016-01-01

    The NCI Bladder Cancer Task Force convened a Clinical Trials Planning Meeting (CTPM) Workshop focused on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer (NMIBC). Meeting attendees included a broad and multi-disciplinary group of clinical and research stakeholders and included leaders from

  18. Are we following the guidelines on non-muscle invasive bladder cancer?

    Directory of Open Access Journals (Sweden)

    Leonardo Oliveira Reis

    2016-02-01

    Full Text Available ABSTRACT Objectives To evaluate the clinical practice of non-muscle invasive bladder cancer (NMIBC treatment in Brazil in relation to international guidelines: Sociedade Brasileira de Urologia (SBU, European Association of Urology (EAU and American Urological Association (AUA. Materials and Methods Cross-sectional study using questionnaires about urological practice on treatment of NMIBC during the 32nd Brazilian Congress of Urology. A total of 650 question forms were answered. Results There were 73% of complete answers (total of 476 question forms. In total, 246 urologists (51.68% lived in the southeast region and 310 (65.13% treat 1 to 3 cases of NMIBC per month. Low risk cancer: Only 35 urologists (7.5% apply the single intravesical dose of immediate chemotherapy with Mitomicin C recommended by the above guidelines. Adjuvant therapy with BCG 2 to 4 weeks after TUR is used by 167 participants (35.1% and 271 urologists (56.9% use only TUR. High risk tumors: 397 urologists (83.4% use adjuvant therapy, 375 (78.8% use BCG 2 to 4 weeks after TUR, of which 306 (64.3% referred the use for at least one year. Intravesical chemotherapy with Mitomicin C (a controversial recommendation was used by 22 urologists (4.6%. BCG dose raised a lot of discrepancies. Induction doses of 40, 80 and 120mg were referred by 105 (22%, 193 (40.4% and 54 (11.3% respectively. Maintenance doses of 40, 80 and 120mg were referred by 190 (48.7%, 144 (37.0% and 32 (8.2% urologists, respectively. Schemes of administration were also varied and the one cited by SWOG protocol was the most used: 142 (29.8%. Conclusion SBU, EAU and AUA guidelines are partially respected by Brazilian urologists, particularly in low risk tumors. In high risk tumors, concordance rates are comparable to international data. Further studies are necessary to fully understand the reasons of such disagreement.

  19. Are we following the guidelines on non-muscle invasive bladder cancer?

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    Reis, Leonardo Oliveira; Moro, Juliano Cesar; Ribeiro, Luis Fernando Bastos; Voris, Brunno Raphael Iamashita; Sadi, Marcos Vinicius

    2016-01-01

    ABSTRACT Objectives To evaluate the clinical practice of non-muscle invasive bladder cancer (NMIBC) treatment in Brazil in relation to international guidelines: Sociedade Brasileira de Urologia (SBU), European Association of Urology (EAU) and American Urological Association (AUA). Materials and Methods Cross-sectional study using questionnaires about urological practice on treatment of NMIBC during the 32nd Brazilian Congress of Urology. A total of 650 question forms were answered. Results There were 73% of complete answers (total of 476 question forms). In total, 246 urologists (51.68%) lived in the southeast region and 310 (65.13%) treat 1 to 3 cases of NMIBC per month. Low risk cancer: Only 35 urologists (7.5%) apply the single intravesical dose of immediate chemotherapy with Mitomicin C recommended by the above guidelines. Adjuvant therapy with BCG 2 to 4 weeks after TUR is used by 167 participants (35.1%) and 271 urologists (56.9%) use only TUR. High risk tumors: 397 urologists (83.4%) use adjuvant therapy, 375 (78.8%) use BCG 2 to 4 weeks after TUR, of which 306 (64.3%) referred the use for at least one year. Intravesical chemotherapy with Mitomicin C (a controversial recommendation) was used by 22 urologists (4.6%). BCG dose raised a lot of discrepancies. Induction doses of 40, 80 and 120mg were referred by 105 (22%), 193 (40.4%) and 54 (11.3%) respectively. Maintenance doses of 40, 80 and 120mg were referred by 190 (48.7%), 144 (37.0%) and 32 (8.2%) urologists, respectively. Schemes of administration were also varied and the one cited by SWOG protocol was the most used: 142 (29.8%). Conclusion SBU, EAU and AUA guidelines are partially respected by Brazilian urologists, particularly in low risk tumors. In high risk tumors, concordance rates are comparable to international data. Further studies are necessary to fully understand the reasons of such disagreement. PMID:27136464

  20. Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Reinert, Thomas; Novoradovsky, A;

    2012-01-01

    Background: Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. Meth...

  1. Identification of C16orf74 as a marker of progression in primary non-muscle invasive bladder cancer.

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    Won Tae Kim

    Full Text Available PURPOSE: Methylation-induced silencing of PRSS3 has been shown to be significantly associated with invasive bladder cancer, and expression of the C16orf74 gene locus has been shown to correlate positively with PRSS3. The aim of the current study was to evaluate the relationship between C16orf74 expression level and progression in non-muscle invasive bladder cancer (NMIBC. MATERIALS AND METHODS: C16orf74 mRNA levels were examined by real-time reverse transcriptase polymerase chain reaction (RT-PCR analysis of 193 tumor specimens from patients with primary NMIBC. Expression data were analyzed in terms of clinical and experimental parameters. Kaplan-Meier curves and multivariate Cox regression models, respectively, were used to determine progression-free survival and to identify independent predictive parameters of progression. RESULTS: Analysis using Kaplan-Meier curves revealed prolonged progression-free survival of high-C16orf74-expressors as compared to low-expressors (p<0.001. Multivariate Cox regression analysis revealed that low C16orf74 mRNA expression levels are a significant risk factor for disease progression in patients with primary NMIBC (HR: 10.042, CI:2.699-37.360, p = 0.001. CONCLUSIONS: Decreased expression of C16orf74 correlates significantly with progression in primary NMIBC. C16orf74 expression level represents a potentially useful marker for predicting progression in primary NMIBC patients.

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

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

    2012-06-01

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

  3. Circulating tumor cells detection has independent prognostic impact in high-risk non-muscle invasive bladder cancer.

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    Gazzaniga, Paola; de Berardinis, Ettore; Raimondi, Cristina; Gradilone, Angela; Busetto, Gian Maria; De Falco, Elena; Nicolazzo, Chiara; Giovannone, Riccardo; Gentile, Vincenzo; Cortesi, Enrico; Pantel, Klaus

    2014-10-15

    High-risk non-muscle invasive bladder cancer (NMIBC) progresses to metastatic disease in 10-15% of cases, suggesting that micrometastases may be present at first diagnosis. The prediction of risks of progression relies upon EORTC scoring systems, based on clinical and pathological parameters, which do not accurately identify which patients will progress. Aim of the study was to investigate whether the presence of CTC may improve prognostication in a large population of patients with Stage I bladder cancer who were all candidate to conservative surgery. A prospective single center trial was designed to correlate the presence of CTC to local recurrence and progression of disease in high-risk T1G3 bladder cancer. One hundred two patients were found eligible, all candidate to transurethral resection of the tumor followed by endovesical adjuvant immunotherapy with BCG. Median follow-up was 24.3 months (minimum-maximum: 4-36). The FDA-approved CellSearch System was used to enumerate CTC. Kaplan-Meier methods, log-rank test and multivariable Cox proportional hazard analysis was applied to establish the association of circulating tumor cells with time to first recurrence (TFR) and progression-free survival. CTC were detected in 20% of patients and predicted both decreased TFR (log-rank p < 0.001; multivariable adjusted hazard ratio [HR] 2.92 [95% confidence interval: 1.38-6.18], p = 0.005), and time to progression (log-rank p < 0.001; HR 7.17 [1.89-27.21], p = 0.004). The present findings provide evidence that CTC analyses can identify patients with Stage I bladder cancer who have already a systemic disease at diagnosis and might, therefore, potentially benefit from systemic treatment.

  4. A panel of prognostic protein markers for progression in non-muscle invasive bladder cancer - a multicenter tissue microarray validation study

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    Fristrup, Niels; Birkenkamp-Demtröder, Karin; Ulhøi, Benedicte Parm

    2012-01-01

    Ta and T1 urothelial carcinomas. Transcripts from the five genes encoding these proteins were previously included in gene expression signatures for outcome prediction for non-muscle invasive bladder cancer (NMIBC). As a training-set, we used primary NMIBC tissue-microarray specimens from a Danish...... cohort of 283 patients with long-term follow-up. For validation of the results we used three independent patient cohorts with long-term follow-up from Sweden, Spain, and Taiwan. In total 649 primary NMIBC tissue-microarray specimens from patients with long-term follow-up were used. Protein expression...

  5. Efficacy and safety of photodynamic therapy for recurrent, high grade nonmuscle invasive bladder cancer refractory or intolerant to bacille Calmette-Guérin immunotherapy.

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    Lee, Joo Yong; Diaz, Richilda Red; Cho, Kang Su; Lim, Meng Shi; Chung, Jae Seung; Kim, Won Tae; Ham, Won Sik; Choi, Young Deuk

    2013-10-01

    We evaluated the effectiveness of photodynamic therapy using Radachlorin in patients with high grade, nonmuscle invasive bladder cancer refractory or intolerant to bacillus Calmette-Guérin therapy who refused radical cystectomy. Between July 2009 and December 2011 photodynamic therapy was performed in 22 men and 12 women. Radachlorin (0.5 to 0.6 mg/kg) was injected intravenously 2 to 3 hours before photodynamic therapy. After complete transurethral resection, a diffuser using a 22Fr cystoscope was placed in the bladder for irradiation with a 662 nm laser. Output beam power was adjusted to 1.8 W and the light dose was 15 J/cm(2). Photodynamic therapy was performed for 16 to 30 minutes. Recurrence after photodynamic therapy was followed by regular cystoscopy at 1, 2 and 3 months, and at 3-month intervals thereafter for up to 2.8 years. Efficacy was assessed by cystoscopy, cytology and histology, and defined as the number of patients who were tumor free after initial photodynamic therapy. Mean ± SD patient age was 62.94 ± 8.71 years. Average followup was 26.74 ± 6.34 months (median 28.12). As the primary efficacy outcome, the recurrence-free rate was 90.9% at 12 months, 64.4% at 24 months and 60.1% at 30 months. As the secondary efficacy outcome, there was no statistical difference in mass size, carcinoma in situ, number of previous bacillus Calmette-Guérin administrations, number of transurethral bladder resections or tumor multiplicity on Kaplan-Meier analysis (each p >0.05). No evidence of severe adverse effects was detected after photodynamic therapy. Photodynamic therapy with Radachlorin is a safe, effective treatment for nonmuscle invasive bladder cancer refractory or intolerant to bacillus Calmette-Guérin therapy in select patients. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-04-27

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

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

    Science.gov (United States)

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

    2016-01-01

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

  8. Gene expression signatures predict outcome in non-muscle invasive bladder carcinoma - a multi-center validation study

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Zieger, Karsten; Real, Francisco X.

    2007-01-01

    PURPOSE: Clinically useful molecular markers predicting the clinical course of patients diagnosed with non-muscle-invasive bladder cancer are needed to improve treatment outcome. Here, we validated four previously reported gene expression signatures for molecular diagnosis of disease stage and ca...

  9. An evaluation of morphological and functional multi-parametric MRI sequences in classifying non-muscle and muscle invasive bladder cancer.

    Science.gov (United States)

    Panebianco, Valeria; De Berardinis, Ettore; Barchetti, Giovanni; Simone, Giuseppe; Leonardo, Constantino; Grompone, Marcello Domenico; Del Monte, Maurizio; Carano, Davide; Gallucci, Michele; Catto, James; Catalano, Carlo

    2017-09-01

    Our goal is to determine the ability of multi-parametric magnetic resonance imaging (mpMRI) to differentiate muscle invasive bladder cancer (MIBC) from non-muscle invasive bladder cancer (NMIBC). Patients underwent mpMRI before tumour resection. Four MRI sets, i.e. T2-weighted (T2W) + perfusion-weighted imaging (PWI), T2W plus diffusion-weighted imaging (DWI), T2W + DWI + PWI, and T2W + DWI + PWI + dif-fusion tensor imaging (DTI) were interpreted qualitatively by two radiologists, blinded to histology results. PWI, DWI and DTI were also analysed quantitatively. Accuracy was determined using histopathology as the reference standard. A total of 82 tumours were analysed. Ninety-six percent of T1-labeled tumours by the T2W + DWI + PWI image set were confirmed to be NMIBC at histopathology. Overall accuracy of the complete mpMRI protocol was 94% in differentiating NMIBC from MIBC. PWI, DWI and DTI quantitative parameters were shown to be significantly different in cancerous versus non-cancerous areas within the bladder wall in T2-labelled lesions. MpMRI with DWI and DTI appears a reliable staging tool for bladder cancer. If our data are validated, then mpMRI could precede cystoscopic resection to allow a faster recognition of MIBC and accelerated treatment pathways. • A critical step in BCa staging is to differentiate NMIBC from MIBC. • Morphological and functional sequences are reliable techniques in differentiating NMIBC from MIBC. • Diffusion tensor imaging could be an additional tool in BCa staging.

  10. A meta-analysis of narrow band imaging for the diagnosis and therapeutic outcome of non-muscle invasive bladder cancer

    Science.gov (United States)

    Ma, ShuJuan; Ge, Jing; Zhou, LiZhi; Li, Dongliang; Chen, Qing

    2017-01-01

    Objectives To assess the additional detection rate (ADR) of within-patient comparisons of Narrow band imaging (NBI) and white light cystoscopy (WLC) for non-muscle invasive bladder cancer (NMIBC) detection and compare the impact of NBI and WLC on bladder cancer recurrence risk. Methods We searched relevant studies from PubMed, Embase, Medline, Web of Science and the Cochrane Library database for all articles in English published beforeJuly26th, 2016. Pooled ADR, diagnostic accuracy, relative risk (RR) and their 95% confidence intervals (CIs) were calculated. Results Twenty-five studies including 17 full texts and eight meeting abstracts were included for analysis. Compared to WLC, pooled ADR of NBI for NMIBC diagnosis was 9.9% (95% CI: 0.05–0.14) and 18.6% (95% CI: 0.15–0.25) in per-patient and per-lesion analysis, respectively. Pooled ADR of NBI for carcinoma in situ (CIS) diagnosis was 25.1% (95% CI: 0.09–0.42) and 31.1% (95% CI: 0.24–0.39) for per-patient and per-lesion analyses, respectively. The pooled sensitivity of NBI was significantly higher than WLC both at the per-patient (95.8% vs. 81.6%) and per-lesion levels (94.8% vs. 72.4%). In addition, NBI significantly reduced the recurrence rate of bladder cancer with a pooled RR value of 0.43 (95% CI: 0.23–0.79) and0.81 (95% CI: 0.69–0.95) at month three and twelve, respectively. Conclusions NBI is a valid technique that improves the diagnosis of NMIBC and CIS compared to standard WLC either at per-patient or per-lesion level. It can reduce the recurrence rate of bladder cancer accordingly. PMID:28192481

  11. Side population in human non-muscle invasive bladder cancer enriches for cancer stem cells that are maintained by MAPK signalling.

    Directory of Open Access Journals (Sweden)

    Anastasia C Hepburn

    Full Text Available Side population (SP and ABC transporter expression enrich for stem cells in numerous tissues. We explored if this phenotype characterised human bladder cancer stem cells (CSCs and attempted to identify regulatory mechanisms. Focusing on non-muscle invasive bladder cancer (NMIBC, multiple human cell lines were used to characterise SP and ABC transporter expression. In vitro and in vivo phenotypic and functional assessments of CSC behaviour were undertaken. Expression of putative CSC marker ABCG2 was assessed in clinical NMIBC samples (n = 148, and a role for MAPK signalling, a central mechanism of bladder tumourigenesis, was investigated. Results showed that the ABCG2 transporter was predominantly expressed and was up-regulated in the SP fraction by 3-fold (ABCG2(hi relative to the non-SP (NSP fraction (ABCG2(low. ABCG2(hi SP cells displayed enrichment of stem cell markers (Nanog, Notch1 and SOX2 and a three-fold increase in colony forming efficiency (CFE in comparison to ABCG2(low NSP cells. In vivo, ABCG2(hi SP cells enriched for tumour growth compared with ABCG2(low NSP cells, consistent with CSCs. pERK was constitutively active in ABCG2(hi SP cells and MEK inhibition also inhibited the ABCG2(hi SP phenotype and significantly suppressed CFE. Furthermore, on examining clinical NMIBC samples, ABCG2 expression correlated with increased recurrence and decreased progression free survival. Additionally, pERK expression also correlated with decreased progression free survival, whilst a positive correlation was further demonstrated between ABCG2 and pERK expression. In conclusion, we confirm ABCG2(hi SP enriches for CSCs in human NMIBC and MAPK/ERK pathway is a suitable therapeutic target.

  12. Novel Simulation Model of Non-Muscle Invasive Bladder Cancer: A Platform for a Virtual Randomized Trial of Conservative Therapy vs. Cystectomy in BCG Refractory Patients.

    Science.gov (United States)

    Patel, Sanjay; Dinh, Tuan; Noah-Vanhoucke, Joyce; Rengarajan, Badri; Mayo, Kevin; Clark, Peter E; Kamat, Ashish M; Lee, Cheryl T; Sexton, Wade J; Steinberg, Gary D

    2015-10-26

    Introduction: There have been no randomized controlled trials (RCTs) evaluating the clinical or economic benefit of mitomycin C intravesical therapy vs. radical cystectomy in patients with high-risk non-muscle invasive bladder cancer (NMIBC). We used the Archimedes computational model to simulate RCT comparing radical cystectomy versus intravesical mitomycin C (MMC) therapy to evaluate the clinical and economic outcomes for BCG-refractory NMIBC as well demonstrate the utility of computer based models to simulate a clinical trial. Methods: The Archimedes model was developed to generate a virtual population using the Surveillance Epidemiology and End Results database, other clinical trials, and expert opinions. Patients selected were diagnosed with NMIBC (virtual patients were evaluation. Progression to MIBC in the MMC treatment arm was 30% over the lifetime. Disease specific death at 5 years was 1.6% and 8.7% for the immediate cystectomy and MMC treatment arms respectively; while, overall death was 17.8% and 23.8% at 5 years. Over a 5-year period the average cost of immediate cystectomy was $64,675 vs $68,517 in the MMC arm. Conclusion: Immediate radical cystectomy after BCG failure for NMIBC has improved survival and is more cost-effective when compared to those undergoing MMC. Simulation of clinical trials using computational models similar to the Archimedes model can overcome shortcomings of real-world clinical trials and may prove useful in the face of current medical cost-conscious era.

  13. p53 Status correlates with the risk of recurrence in non-muscle invasive bladder cancers treated with Bacillus Calmette-Guerin: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xiaofeng Zhou

    Full Text Available Published studies have yielded inconsistent results on the relationship between p53 status and the prognosis of non-muscle invasive bladder cancer (NMIBC treated with Bacillus Calmette-Guérin (BCG intravesical therapy. Therefore, we performed a meta-analysis to evaluate the prognostic value of p53 in NMIBC treated with BCG.We systematically searched for relevant literature in PubMed, EMBASE, CNKI, and Chinese Wanfang databases. Hazard ratios (HRs with 95% confidence intervals (CIs were combined as the effect size (ES across studies for recurrence-free survival (RFS and progression-free survival (PFS.A total of 11 studies, consisting of 1,049 participants, met the criteria. Overall, there was no clear relationship between p53 status and RFS or PFS for NMIBC patients treated with BCG (HR: 1.40, 95% CI: 0.91-2.16; HR: 1.37, 95% CI: 0.90-2.09, respectively. Obvious heterogeneity was observed across the studies (I2 = 69.5%, P = 0.001; I2 = 44.7%, P = 0.081, respectively. In stratified analysis by region, p53 overexpression was a predictor of poor RFS in Asian populations (HR: 1.57, 95% CI: 1.08-2.27. In addition, after excluding the studies that possibly contributed to the heterogeneity by the Galbraith plot, the overall association for RFS became statistically significant (HR: 1.38 95% CI: 1.08-1.77 without evidence of heterogeneity (I2 = 0.0%, P = 0.499.This meta-analysis suggests that p53 overexpression in NMIBC patients treated with BCG may be associated with RFS, especially in Asian populations. Because of the heterogeneity and other limitations, further studies with rigid criteria and large populations are still warranted to confirm our findings.

  14. Ki-67 is an independent indicator in non-muscle invasive bladder cancer (NMIBC); combination of EORTC risk scores and Ki-67 expression could improve the risk stratification of NMIBC.

    Science.gov (United States)

    Ding, Weihong; Gou, Yuancheng; Sun, Chuanyu; Xia, Guowei; Wang, Hong; Chen, Zhongqing; Tan, Jun; Xu, Ke; Qiang, Ding

    2014-01-01

    To prove the predicting role of Ki-67 expression and to demonstrate that the combination of European Organization for Research and Treatment of Cancer (EORTC) risk scores and Ki-67 staining status could improve the risk stratification in a large series of patients with non-muscle invasive bladder cancer (NMIBC). From October 2002 to July 2010, in our cohort, 332 patients who were treated with transurethral resection of the bladder tumor were diagnosed with NMIBC by histopathologic analysis. Two experienced uropathologists rereviewed the slides. The EORTC risk scores for recurrence and progression were determined. Ki-67 expression was evaluated using immunohistochemical studies and scored for intensity and area of staining. We correlated Ki-67 expression scores with clinical and pathologic variables. We evaluated the prognosis role of EORTC risk scores, Ki-67 staining, and their combination on tumor recurrence-free survival and progression-free survival (PFS) by univariate analysis, multivariate analysis, and Kaplan-Meier survival curves. With a median follow-up of 47 (range, 2-124) months, 119 patients (35.8%) had tumor recurrence and 40 patients (12%) had tumor progression. Ki-67 positivity (Ki-67>25%) was reported in 108 tumors (32.5%), and it was significantly associated with high EORTC risk scores for both tumor recurrence and progression. In univariate analysis, multifocality, tumor size, tumor stage, tumor grade, and Ki-67 staining correlated with recurrence-free survival, whereas tumor size, tumor stage, tumor grade, concomitant CIS, and Ki-67 staining correlated with PFS. In multivariable analysis, Ki-67 expression was an independent risk factor for predicting tumor recurrence (hazard ratio, 2.14; PEORTC risk scores and Ki-67 staining led to more accurate prediction for tumor recurrence and progression (log-rank test; PEORTC risk scores with Ki-67 expression could improve the risk stratification for both recurrence and progression in NMIBC. Copyright

  15. Alterations in ubiquitin ligase Siah-2 and its corepressor N-CoR after P-MAPA immunotherapy and anti-androgen therapy: new therapeutic opportunities for non-muscle invasive bladder cancer.

    Science.gov (United States)

    Garcia, Patrick Vianna; Apolinário, Letícia Montanholi; Böckelmann, Petra Karla; da Silva Nunes, Iseu; Duran, Nelson; Fávaro, Wagner José

    2015-01-01

    The present study describes the role of the ubiquitin ligase Siah-2 and corepressor N-CoR in controlling androgen receptor (AR) and estrogen receptors (ERα and ERβ) signaling in an appropriate animal model (Fischer 344 female rats) of non-muscle invasive bladder cancer (NMIBC), especially under conditions of anti-androgen therapy with flutamide. Furthermore, this study describes the mechanisms of a promising therapeutic alternative for NMIBC based on Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride (P-MAPA) intravesical immunotherapy combined with flutamide, involving the interaction among steroid hormone receptors, their regulators and Toll-like receptors (TLRs). Our results demonstrated that increased Siah-2 and AR protein levels and decreased N-CoR, cytochrome P450 (CYP450) and estrogen receptors levels played a critical role in the urothelial carcinogenesis, probably leading to escape of urothelial cancer cells from immune system attack. P-MAPA immunotherapy led to distinct activation of innate immune system TLRs 2 and 4-mediated, resulting in increase of interferon signaling pathway, which was more effective in recovering the immunosuppressive tumor immune microenvironment and in recovering the bladder histology features than BCG (Bacillus Calmette-Guerin) treatments. The AR blockade therapy was important in the modulating of downstream molecules of TLR2 and TLR4 signaling pathway, decreasing the inflammatory cytokines signaling and enhancing the interferon signaling pathway when associated with P-MAPA. Taken together, the data obtained suggest that interferon signaling pathway activation and targeting AR and Siah-2 signals by P-MAPA intravesical immunotherapy alone and/ or in combination with AR blockade may provide novel therapeutic approaches for NMIBC.

  16. A panel of prognostic protein markers for progression in non-muscle invasive bladder cancer - a multicenter tissue microarray validation study

    DEFF Research Database (Denmark)

    Fristrup, Niels; Birkenkamp-Demtröder, Karin; Ulhøi, Benedicte Parm;

    2012-01-01

    Bladder cancer is the fifth most common cancer in the Western world. The histopathological parameters used in the clinic cannot precisely predict the individual disease course. Bladder cancer patients are therefore monitored thoroughly for disease recurrence and progression by urine and cystoscop...

  17. The application of adjuvant autologous antravesical macrophage cell therapy vs. BCG in non-muscle invasive bladder cancer: a multicenter, randomized trial

    Directory of Open Access Journals (Sweden)

    Kiss Tamas

    2010-06-01

    Full Text Available Abstract Introduction While adjuvant immunotherapy with Bacille Calmette Guérin (BCG is effective in non-muscle-invasive bladder cancer (BC, adverse events (AEs are considerable. Monocyte-derived activated killer cells (MAK are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM® to BCG in patients after transurethral resection (TURB of BC. Materials and methods This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and ≥ 2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM. Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint and prophylactic effects (secondary endpoint were assessed. Results Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE, respectively (p Discussion This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted. Trial registration The trial has been registered in the ISRCTN registry http://isrctn.org under the registration number ISRCTN35881130.

  18. The clinical course of non-muscle invasive bladder cancer after transuretral resection of the tumor with or without subsequent intravesical application of bacillus Calmette-Guérin: The influence of patients gender and age

    Directory of Open Access Journals (Sweden)

    Milošević Radovan

    2015-01-01

    Full Text Available Bacground/Aim. The therapy with intravesical instillation of bacillus Calmette-Guérin (BCG after transurethral resection (TUR of tumor is the gold standard of treatment of non-muscle invasive bladder cancer (NMIBC. The role and importance of BCG intravesical therapy in various shape of tumors, were confirmed by our previous investigation. The aim of this study was to examine whether incidence of recurrence and tumor regression differs depending on sex and age of patients. Methods. This study included a total of 899 patients suffering from NIMBC, treated at our institution from January 1, 2007 to March 1, 2013. Two groups of patients were formed: patients underwent TUR + BCG therapy (the group I and the group II with patients in whom TUR was performed as only therapy. These two groups of patients were divided into subgroups of respondents male and female, age 60 years or younger and older than 60 years. Statistical analysis was performed using χ2 test and the Kolmogorov-Smirnov test. Results. This research suggests that if the frequency of recurrence is seen as the only parameter, considering all the subjects, the lowest recurrence rate was determined in the male subjects, aged 60 years and younger who had received BCG after TUR. A high statistical significance was found in the incidence of recurrence in patients younger than 60 years, depending on the response to the therapy, while in those older than 60 years, the difference was at the level of statistical significance. This can be attributed to a certain degree of infravesical obstruction in older men. Conclusions. Sex and age of patients may have a significant influence on the course and outcome of NMIBC. The disease has the most malignant and most aggressive behavior when present in males older than 60 years.

  19. Do Standardised Prognostic Algorithms Reflect Local Practice? Application of EORTC Risk Tables for Non-Muscle Invasive (pTa/pT1 Bladder Cancer Recurrence and Progression in a Local Cohort

    Directory of Open Access Journals (Sweden)

    Rajiv Pillai

    2011-01-01

    Full Text Available A risk calculator algorithm to allow prediction of probabilities of 1- and 5-year recurrence and progression rates in individuals with pTa/pT1 bladder cancer has been proposed by the European Organisation for Research and Treatment of Cancer (EORTC and was incorporated into the European Association of Urology guidelines in 2006. We attempted to validate this algorithm in a cohort of patients with known outcome. Prognostic data were collected from a consecutively presenting cohort of 109 patients with non-muscle invasive (pTa/pT1 transitional cell cancer (TCC at a single institution between 1983 and 1985. Using the same statistical models as in the EORTC original paper, predicted probabilities of 1- and 5-year recurrence and progression were calculated. Patients were divided into four risk groups for recurrence (Ir-IVr and progression (Ip-IVp, respectively, using six prognostic criteria. These were then compared to the probabilities predicted in the EORTC algorithm. The predicted 1- and 5-year probabilities of recurrence were significantly higher in the study population as compared to the original EORTC algorithm for all four risk groups. The predicted 1-year probabilities for progression in groups Ip/IIIp and at 5-years for groups Ip/IIp were in accordance with the original algorithm, but were higher for the other progression groups. The concordance for the model of prediction using the study group for recurrence at 1 and 5 years was 62 and 63%, respectively, and for progression was 65 and 67, respectively. We were unable to validate the proposed algorithm in our group of patients. Although our study has limitations that prevent firm conclusions on the validity of the algorithm, it does expose some of the drawbacks of standardised nomograms when applied to local clinical practice.

  20. Urovysion™ testing can lead to early identification of intravesical therapy failure in patients with high risk non-muscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Jared M. Whitson

    2009-12-01

    Full Text Available Purpose: In this study, we investigated the ability of UroVysion™ to assess response to intravesical therapy in patients with high risk superficial bladder tumors. Materials and methods: We performed a retrospective review of patients undergoing intravesical therapy for high risk superficial bladder tumors. Urine specimens were collected for UroVysion™ analysis before and immediately after a course of intravesical therapy. Cytology and cystoscopy were performed six weeks after treatment, using either a positive cytology or visible abnormality on cystoscopy as a prompt for biopsy. The operating characteristics of the UroVysion™ test were then determined. Results: 41 patients were identified in whom 47 cycles of induction and 41 cycles of maintenance intravesical therapy were given during the study period. This yielded a total of 88 treatment and evaluation cycles. Median follow-up was 9 months per induction (range 1-21 months and 13 months per patient (range 1-25 months. A total of 133 urine samples were collected for UroVysion™ of which 40 were positive. Based upon standard clinical evaluation, 41 biopsies were performed which detected 20 recurrences. UroVysion™ testing performed immediately upon completion of therapy for the 41 patients undergoing biopsy yielded a sensitivity, specificity, and accuracy of 85%, 61%, and 71%. Conclusions: The use of UroVysion™ following intravesical therapy for high-risk superficial bladder tumors helps to identify patients at high risk of refractory or recurrent disease who should undergo immediate biopsy under anesthesia.

  1. 经尿道红激光汽化切除治疗非肌层浸润性膀胱癌30例疗效观察%Efficacy report of 30 cases about transurethral red laser vaporization resecting for non-muscle invasive bladder cancer

    Institute of Scientific and Technical Information of China (English)

    孙浩洋; 李明; 李宝龙

    2015-01-01

    目的:探讨经尿道红激光汽化切除治疗非肌层浸润性膀胱癌的疗效。方法对30例非肌层浸润性膀胱癌患者,采用980 nm 红激光治疗仪汽化切除包括肿瘤基底部及周围2 cm 范围的浅肌层膀胱组织,术后即刻进行膀胱灌注盐酸吡柔比星局部化疗。结果全部患者手术均获成功,平均出血量小于5 ml,无膀胱穿孔、闭孔神经反射及稀释性低钠血症的发生。随访6~20个月,7例患者术后复发,再次行经尿道红激光膀胱肿瘤汽化切除。结论经尿道红激光汽化切除治疗非肌层浸润性膀胱癌是一种安全、微创、出血量极少的治疗方法,疗效显著,并发症少。%Objective To investigate the effect of transurethral red laser vaporization resecting for non-muscle invasive bladder cancer. Methods 30 patients with non-muscle invasive bladder cancer were collected.Setting red laser resectoscope into the urethra,turning Germany 980 nm red laser treatment EVOLVE TM-HPD∗ (Hi-Power Diode)to power 120 w to resect the tumor vapor-izedly.Intravesical instillation of hydrochloric acid Pirarubicin was taken immediately after the sur-gery. Results All cases were successful surgery,no bladder perforation and obturator nerve reflex occurs.Follow-up during 6 to 20 months,7 patients recurrence,transurethral red laser vaporization resecting were taken again. Conclusions Transurethral red laser vaporization resecting for non-muscle invasive bladder cancer is a safe,minimally invasive treatment with minimal blood loss and few complications.

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

    Science.gov (United States)

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

    2014-01-01

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

  3. Feasibility study of early localization diagnosis of THP (pirarubicin) on non-muscle invasive bladder cancer%THP定位诊断早期非肌层浸润性膀胱癌

    Institute of Scientific and Technical Information of China (English)

    张万峰; 王贵平; 王洪杰; 丁晓晖; 刘会恩; 曲嘉林; 王百峰; 杨振涛

    2011-01-01

    目的:研究THP(吡柔比星)对非肌层浸润性膀胱癌早期的定位诊断效果.方法:选择35例已诊断膀胱癌或高度怀疑尿路上皮癌患者.病人术前及术后复查时,30mgTHP溶入50ml 5%葡萄糖液中,灌入已排空的膀胱中,保留15分钟,排出THP,彻底冲洗膀胱.普通膀胱镜检查,有THP吸收的非肿瘤区域取活检,无THP吸收的部位随机活检.结果:35例患者中存在非肌层浸润性膀胱癌早期的共6例.结论:THP对非肌层浸润性膀胱癌早期的定位诊断效果明确,安全性好.%Objective : To study the feasibility of early localization diagnosis of THP ( pirarubicin) on non - muscle invasive bladder cancer. Methods : For 35 patients that had the diagnosis of bladder cancer or was highly suspected had carcinoma of urethra epidermis,before or after surgery , integrate 30mg THP into the 50ml 5% glucose,pour the glucose into empty bladder and keep it for 15 minutes,drain and rinse the bladder thoroughly. With normal cystoscopy, the region with absorption of THP of non - tumor do biopsy and non - absorbed part of THP do random biopsy. Results : In 31 patients , there were 6 had early non - muscle invasive bladder cancer. Conclusion : For non - muscle invasive bladder cancer the early localization diagnosis of THP is clear and safe.

  4. Clinical significance of simultaneous transurethral resection of a bladder tumor and the prostate in the treatment of non-muscle invasive bladder cancer with benign prostatic hyperplasia%非肌层浸润性膀胱癌合并良性前列腺增生患者同期行经尿道电切手术的疗效和安全性分析

    Institute of Scientific and Technical Information of China (English)

    陈海昕; 张冠; 方自林; 王翔; 刘乃波

    2011-01-01

    Objective To evaluate the clinical significance of simultaneous transurethral resection (TUR) of a bladder tumor and the prostate in the treatment of non-muscle invasive bladder cancer with benign prostatic hyperplasia (BPH).Methods Patients were divided into two groups.Group A contained 46 male patients who accepted TUR for the treatment of both bladder cancer and benign prostatic hyperplasia.Group B contained 69 male patients who accepted TURBt only.Clinical data were retrospectively collected and analyzed to compare clinical outcomes and safety in these two groups.Results The bladder cancer recurrence rates in group A and B were 50.0% and 50.7%,the average recurrence free time was 20 and 18 months,and the progression rates were 6.5% and 7.2%,respectively.There were no significant differences between the two groups for either average recurrence free time or progression rates (P > 0.05).Recurrences in the prostatic urethra were found in two cases in group A and one case in group B and all three cases were in T1 G3.Conclusions Simultaneous TUR for bladder tumor and the prostate can be safely and effectively performed in terms of oncologica] control in patients who have non-muscle invasive and low grade bladder tumors ( T1G1 - G2 ) with lower urinary tract obstruction caused by BPH.But this procedure should be cautiously performed on patients with T1 G3 bladder tumors.%目的 探讨合并BPH的非肌层浸润性膀胱癌患者同期行经尿道电切(TUR)手术的疗效和安全性.方法 合并BPH的非肌层浸润性膀胱癌患者46例(A组)同期行TURBt和TURP治疗,非肌层浸润性膀胱癌仅行TURBt的男性患者69例(B组)作为对照组.A组年龄54~80岁,平均69岁;肿瘤单发37例、多发9例,肿瘤直径0.5 ~3.5 cm,平均2.8 cm.B组55~82岁,平均70岁;肿瘤单发54例、多发15例;肿瘤直径0.5~24.0 cm,平均2.9 cm;2组比较差异无统计学意义(P>0.05).结果 2组均顺利完成手术.随访24 - 96个月,平均44

  5. Significance Disscuss of Transurethral Resection Secondary Treatment of Non-muscle Invasive Bladder Cancer%经尿道二次电切治疗非肌层浸润性膀胱肿瘤的意义探讨

    Institute of Scientific and Technical Information of China (English)

    吴卫星

    2014-01-01

    Objective:To study the muscular layer in invasive bladder cancer treatment,the clinical effect of transurethral secondary cutting treatment.Method:50 patients after transurethral plasmakentic vaporization of electricity cut for the first time were selected,and they were muscularis invasive bladder cancer by pathological diagnosis,all patients underwent secondary electricity cut method ofter 4-6 weeks,the cancer histopathological characteristics after the primary surgery and the second postoperative were compared.Result:After treatment for secondary,in 50 patients,21 cases of tumor survival,20 cases found tumor residual lesions,6 cases found tumor missed lesions,5 patients already exists residual lesions and missed lesions. After treatment from the pathological staging,21 cases of tumor survival,10 cases of Ta,11 cases of T1 phase,8 cases progressed to T2 stage. Through the clinical analyzed,single factor and multiple factors that T1 phase,high grade and tumor diameter>3 cm were secondary electric cut operation pathological staging to T2 stage independent risk factors.Conclusion:Transurethral secondary cutting treatment,which can effectively improve the patient’s quality of life,the T1 phase,high grade and tumor>3 cm in diameter is independent risk factors in the development of disease,clinical should take seriously.%目的:探讨非肌层浸润性膀胱肿瘤治疗中,经尿道二次电切治疗的临床效果。方法:选取本院50例初次行经尿道电切之后,病理诊断为非肌层浸润性膀胱癌患者,全部患者于术后4~6周行二次电切术,比较初次手术与二次术后的肿瘤组织病理学特点。结果:经二次治疗后,50例患者中,21例无肿瘤生存,20例发现肿瘤残余病灶,6例发现肿瘤遗漏病灶,5例既存在残留病灶又存在遗漏病灶。治疗后从病理分期看,21例无肿瘤生存,10例为Ta期,11例为T1期,8例进展至T2期。经临床单因素

  6. Oncologic Outcomes of Kidney-sparing Surgery Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by the EAU Non-muscle Invasive Bladder Cancer Guidelines Panel.

    Science.gov (United States)

    Seisen, Thomas; Peyronnet, Benoit; Dominguez-Escrig, Jose Luis; Bruins, Harman M; Yuan, Cathy Yuhong; Babjuk, Marko; Böhle, Andreas; Burger, Maximilian; Compérat, Eva M; Cowan, Nigel C; Kaasinen, Eero; Palou, Joan; van Rhijn, Bas W G; Sylvester, Richard J; Zigeuner, Richard; Shariat, Shahrokh F; Rouprêt, Morgan

    2016-12-01

    There is uncertainty regarding the oncologic effectiveness of kidney-sparing surgery (KSS) compared with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). To systematically review the current literature comparing oncologic outcomes of KSS versus RNU for UTUC. A computerised bibliographic search of the Medline, Embase, and Cochrane databases was performed for all studies reporting comparative oncologic outcomes of KSS versus RNU. Approaches considered for KSS were segmental ureterectomy (SU) and ureteroscopic (URS) or percutaneous (PC) management. Using the methodology recommended by the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, we identified 22 nonrandomised comparative retrospective studies published between 1999 and 2015 that were eligible for inclusion in this systematic review. A narrative review and risk-of-bias (RoB) assessment were performed using cancer-specific survival (CSS) as the primary end point. Seven studies compared KSS overall (n=547) versus RNU (n=1376). Information on the comparison of SU (n=586) versus RNU (n=3692), URS (n=162) versus RNU (n=367), and PC (n=66) versus RNU (n=114) was available in 10, 5, and 2 studies, respectively. No significant difference was found between SU and RNU in terms of CSS or any other oncologic outcomes. Only patients with low-grade and noninvasive tumours experienced similar CSS after URS or PC when compared with RNU, despite an increased risk of local recurrence following endoscopic management of UTUC. The RoB assessment revealed, however, that the analyses were subject to a selection bias favouring KSS. Our systematic review suggests similar survival after KSS versus RNU only for low-grade and noninvasive UTUC when using URS or PC. However, selected patients with high-grade and invasive UTUC could safely benefit from SU when feasible. These results should be interpreted with caution due to the risk of selection bias. We reviewed the studies that

  7. MicroRNA Expression Profile Identifies High Grade, Non-Muscle-Invasive Bladder Tumors at Elevated Risk to Progress to an Invasive Phenotype

    Science.gov (United States)

    Lenherr, Sara M.; Tsai, Sheaumei; Silva Neto, Brasil; Sullivan, Travis B.; Cimmino, Cara B.; Logvinenko, Tanya; Gee, Jason; Huang, Wei; Libertino, John A.; Summerhayes, Ian C.; Rieger-Christ, Kimberly M.

    2017-01-01

    The objective of this study was to identify a panel of microRNAs (miRNAs) differentially expressed in high-grade non-muscle invasive (NMI; TaG3–T1G3) urothelial carcinoma that progress to muscle-invasive disease compared to those that remain non-muscle invasive, whether recurrence happens or not. Eighty-nine high-grade NMI urothelial carcinoma lesions were identified and total RNA was extracted from paraffin-embedded tissue. Patients were categorized as either having a non-muscle invasive lesion with no evidence of progression over a 3-year period or as having a similar lesion showing progression to muscle invasion over the same period. In addition, comparison of miRNA expression levels between patients with and without prior intravesical therapy was performed. Total RNA was pooled for microarray analysis in each group (non-progressors and progressors), and qRT-PCR of individual samples validated differential expression between non-progressive and progressive lesions. MiR-32-5p, -224-5p, and -412-3p were associated with cancer-specific survival. Downregulation of miR-203a-3p and miR-205-5p were significantly linked to progression in non-muscle invasive bladder tumors. These miRNAs include those implicated in epithelial mesenchymal transition, previously identified as members of a panel characterizing transition from the non-invasive to invasive phenotype in bladder tumors. Furthermore, we were able to identify specific miRNAs that are linked to postoperative outcome in patients with high grade NMI urothelial carcinoma of the bladder (UCB) that progressed to muscle-invasive (MI) disease. PMID:28218662

  8. Combined thermo-chemotherapy for recurrent bladder cancer after bacillus Calmette-Guerin.

    NARCIS (Netherlands)

    Nativ, O.; Witjes, J.A.; Hendricksen, K.; Cohen, M.; Kedar, D.; Sidi, A.; Colombo, R.; Leibovitch, I.

    2009-01-01

    PURPOSE: Despite an initial adequate response many patients with nonmuscle invasive urothelial cell carcinoma of the bladder eventually have recurrence after intravesical bacillus Calmette-Guerin treatments. We evaluated the efficacy of combined bladder wall hyperthermia and intravesical mitomycin C

  9. The Use of Regenerative Medicine in the Management of Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Matthew E. Hyndman

    2012-01-01

    Full Text Available Muscle invasive and recurrent nonmuscle invasive bladder cancers have been traditionally treated with a radical cystectomy and urinary diversion. The urinary diversion is generally accomplished through the creation of an incontinent ileal conduit, continent catheterizable reservoir, or orthotopic neobladder utilizing small or large intestine. While radical extirpation of the bladder is often successful from an oncological perspective, there is a significant morbidity associated with enteric interposition within the genitourinary tract. Therefore, there is a great opportunity to decrease the morbidity of the surgical management of bladder cancer through utilization of novel technologies for creating a urinary diversion without the use of intestine. Clinical trials using neourinary conduits (NUC seeded with autologous smooth muscle cells are currently in progress and may represent a significant surgical advance, potentially eliminating the complications associated with the use of gastrointestinal segments in the urinary reconstruction, simplifying the surgical procedure, and greatly facilitating recovery from cystectomy.

  10. Innovation in Bladder Cancer Immunotherapy.

    Science.gov (United States)

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

    2016-10-01

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

  11. Neoadjuvant chemotherapy for invasive bladder cancer.

    Science.gov (United States)

    Sonpavde, Guru; Sternberg, Cora N

    2012-04-01

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

  12. Placenta previa percreta with bladder invasion

    Directory of Open Access Journals (Sweden)

    Siniša Šijanović

    2011-02-01

    Full Text Available A 43- year old woman, with ten previous deliveries and history of two cesarean sections was admitted to our Department at 32 weeks of gestation with massive vaginal hemorrhage from an ultrasound diagnosed placenta previa. An emergency cesarean section with vertical abdominal incision was performed. A healthy 2300 g female infant was delivered. Attempts to manually remove the placenta caused massive hemorrhage. The lower uterine segment was widened due to placenta previa with suspicious placental invasion of the posterior wall of the bladder. Persistent hemorrhage demanded bilateral anterior internal iliac artery ligation and suture ligation of the bleeding vessels with supracervical hysterectomy done.

  13. ILEOCYSTOPLASTY IN INVASIVE URINARY BLADDER CARCINOMA

    Directory of Open Access Journals (Sweden)

    V. N. Pavlov

    2009-01-01

    Full Text Available Objective: to assess the results of surgical treatment of patients with the intestinal urinary bladder, to characterize its early and late postoperative complications, and to develop their correction tactics.  Subjects and methods. The results of treatment in 198 patients who had undergone ileocystoplasty were analyzed.  Results. The developed diagnostic approach and the determined examination periods could reduce the number of late postoperative complications of ileocystoplasty: acute and chronic pyelonephritis from 19.4 to 7.6%, urolithiasis from 17.2 to 1.9%, bladder dysfunction from 25.8 to 7.6%, and metabolic acidosis from 4.3 to 1.9%, and prevent the development of ureterovesical anastomosis stricture.  Conclusion. Radical cystectomy with the ileoplasty using an isolated segment of the ileum in patients with invasive urinary bladder carcinoma has been the operation of choice no longer; it has become an essential surgical adjunct. This method permits overall 5-year survival to be achieved in 69.7% of patients.  

  14. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013.

    Science.gov (United States)

    Babjuk, Marko; Burger, Maximilian; Zigeuner, Richard; Shariat, Shahrokh F; van Rhijn, Bas W G; Compérat, Eva; Sylvester, Richard J; Kaasinen, Eero; Böhle, Andreas; Palou Redorta, Joan; Rouprêt, Morgan

    2013-10-01

    diagnosis and treatment of NMIBC for incorporation into clinical practice. The EAU Panel on Non-muscle Invasive Bladder Cancer released an updated version of their guidelines. Current clinical studies support patient selection into different risk groups; low, intermediate and high risk. These risk groups indicate the likelihood of the development of a new (recurrent) cancer after initial treatment (endoscopic resection) or progression to more aggressive (muscle-invasive) bladder cancer and are most important for the decision to provide chemo- or immunotherapy (bladder installations). Surgical removal of the bladder (radical cystectomy) should only be considered in patients who have failed chemo- or immunotherapy, or who are in the highest risk group for progression. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  15. Placenta Percreta With Invasion into the Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Zachary L. Smith

    2014-01-01

    Full Text Available Placenta percreta is a rare condition, which can lead to significant morbidity and potentially mortality. We present a case of a 38-year-old woman who presented at 24 weeks gestation with vaginal bleeding and was found to have complete placenta previa with placenta percreta invading the urinary bladder. Her hospital course was complicated by bilateral pulmonary emboli. She underwent an exploratory laparotomy, repeat Caesarean section, and total abdominal hysterectomy. Because of placental invasion into the bladder, the procedure was complicated by bladder and ureteral injuries for which urology carried out repair. Postoperatively, the patient had a persistent bladder leak until postoperative day #39.

  16. Developments in diagnosis and prognosis of superficial bladder cancer

    NARCIS (Netherlands)

    Moonen, P.M.J.

    2007-01-01

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

  17. BCG Induced Necrosis of the Entire Bladder Urothelium

    Directory of Open Access Journals (Sweden)

    Malte Krönig

    2015-09-01

    Full Text Available Instillation therapy with attenuated tuberculosis bacteria (BCG can significantly reduce rates of recurrence of non-muscle invasive bladder cancer. Local and systemic side effects such as dysuria, irritative voiding symptoms or partial bladder contracture and systemic inflammation were reported. A 75 year-old male patient with recurrent non muscle invasive bladder cancer developed necrosis of the entire bladder urothelium more than six years after BCG instillation immunotherapy. The resulting irritative voiding symptoms and low bladder capacity required radical cystectomy. BCG instillation can cause severe side effects, which develop gradually and eventually need radical surgical therapy such as cystectomy without tumor recurrence.

  18. Novel non invasive diagnostic strategies in bladder cancer.

    Science.gov (United States)

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

    2016-01-01

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

  19. Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Kari T. Syvänen

    2014-05-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

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

    DEFF Research Database (Denmark)

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

    1995-01-01

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

  2. Current therapeutic strategies for invasive and metastatic bladder cancer

    Directory of Open Access Journals (Sweden)

    Vishnu P

    2011-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-02-01

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

  4. Holmium laser transurethral resection of bladder tumor: Our experience

    Directory of Open Access Journals (Sweden)

    Nischith D'souza

    2016-01-01

    Conclusions: HoL-EBRBT might prove to be preferable alternatives to CM-TURBT management of nonmuscle-invasive bladder cancer. HoL-EBRBT however did not demonstrate an obvious advantage over CM-TURBT in tumor recurrence rate.

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

    Science.gov (United States)

    Skinner, Eila C

    2016-01-01

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

  6. Proteomics research on muscle-invasive bladder transitional cell carcinoma

    Directory of Open Access Journals (Sweden)

    Cao Yan

    2011-06-01

    Full Text Available Abstract Background Aimed to facilitate candidate biomarkers selection and improve network-based multi-target therapy, we perform comparative proteomics research on muscle-invasive bladder transitional cell carcinoma. Laser capture microdissection was used to harvest purified muscle-invasive bladder cancer cells and normal urothelial cells from 4 paired samples. Two-dimensional liquid chromatography tandem mass spectrometry was used to identify the proteome expression profile. The differential proteins were further analyzed using bioinformatics tools and compared with the published literature. Results A total of 885/890 proteins commonly appeared in 4 paired samples. 295/337 of the 488/493 proteins that specific expressed in tumor/normal cells own gene ontology (GO cellular component annotation. Compared with the entire list of the international protein index (IPI, there are 42/45 GO terms exhibited as enriched and 9/5 exhibited as depleted, respectively. Several pathways exhibit significantly changes between cancer and normal cells, mainly including spliceosome, endocytosis, oxidative phosphorylation, etc. Finally, descriptive statistics show that the PI Distribution of candidate biomarkers have certain regularity. Conclusions The present study identified the proteome expression profile of muscle-invasive bladder cancer cells and normal urothelial cells, providing information for subcellular pattern research of cancer and offer candidate proteins for biomarker panel and network-based multi-target therapy.

  7. High-Risk Non-Muscle-Invasive Bladder Cancer-Therapy Options During Intravesical BCG Shortage.

    Science.gov (United States)

    Veeratterapillay, Rajan; Heer, Rakesh; Johnson, Mark I; Persad, Raj; Bach, Christian

    2016-09-01

    Bladder cancer is the second commonest urinary tract malignancy with 70-80 % being non-muscle invasive (NMIBC) at diagnosis. Patients with high-risk NMIBC (T1/Tis, with high grade/G3, or CIS) represent a challenging group as they are at greater risk of recurrence and progression. Intravesical Bacilli Calmette-Guerin (BCG) is commonly used as first line therapy in this patient group but there is a current worldwide shortage. BCG has been shown to reduce recurrence in high-risk NMIBC and is more effective that other intravesical agents including mitomycin C, epirubicin, interferon-alpha and gemcitabine. Primary cystectomy offers a high change of cure in this cohort (80-90 %) and is a more radical treatment option which patients need to be counselled carefully about. Bladder thermotherapy and electromotive drug administration with mitomycin C are alternative therapies with promising short-term results although long-term follow-up data are lacking.

  8. miR-34a inhibits proliferation and invasion of bladder cancer cells by targeting orphan nuclear receptor HNF4G.

    Science.gov (United States)

    Sun, Huaibin; Tian, Jun; Xian, Wanhua; Xie, Tingting; Yang, Xiangdong

    2015-01-01

    miR-34a is a member of the miR-34 family and acts as a tumor suppressor in bladder cancer. This study explored the regulative role of miR-34a on an orphan nuclear receptor HNF4G, which has a well-confirmed role in bladder tumor growth and invasion. qRT-PCR analysis was applied to measure miR-34a expression in two tumorigenic bladder cancer cell lines 5637 and T24 and one normal human urothelial cell line SV-HUC-1. Luciferase assay was performed to verify the putative binding between miR-34a and HNF4G. The influence of miR-34a-HNF4G axis on cell viability, colony formation, and invasion was assessed with loss- and gain-of-function analysis. This study observed that the miR-34a expressions in 5637 and T24 cells were significantly lower than in SV-HUC-1, while the muscle invasive cell sublines 5637-M and T24-M had even lower miR-34a expression than in the nonmuscle invasive sublines. HNF4G has a 3'-UTR binding site with miR-34a and is a direct downstream target of miR-34a. miR-34a can directly downregulate the expression of HNF4G and thus inhibit tumor cell viability, colony formation, and invasion. Therefore, miR-34a-HNF4G axis is an important pathway modulating cell viability, proliferation, and invasion of bladder cancer cells.

  9. Identification of pro-inflammatory cytokines associated with muscle invasive bladder cancer; the roles of IL-5, IL-20, and IL-28A.

    Directory of Open Access Journals (Sweden)

    Se-Jung Lee

    Full Text Available We used gene expression profiling to identify inflammatory cytokines that correlate with bladder cancer development. Gene expression profiles of the tissue samples were investigated using cDNA microarrays that contained 103 non-muscle invasive bladder cancers (NMIBC, 62 muscle invasive bladder cancers (MIBC, 58 samples of histologically normal-looking surrounding tissues, and 10 normal, healthy subjects who served as the control cohort for comparison. We grouped the data-sets according to biological characterizations and focused on immune response genes with at least 2-fold differential expression in MIBC vs. controls. The experimental data-set identified 36 immune-related genes that were significantly altered in MIBC samples. In addition, 10 genes were up-regulated and 26 genes were down-regulated in MIBC samples compared with the normal tissues. Among the 10 up-regulated molecules examined, the capacity for both wound-healing migration and invasion was enhanced in response to IL-5, IL-20, and IL-28A in bladder cancer cell lines (253J and EJ cells, compared with untreated cells. The expression levels of IL-5, IL-20, and IL-28A were increased in patients with MIBC. All 3 cytokines and their receptors were produced in bladder cancer cell lines, as determined by real-time PCR, immunoblot analysis and confocal immunofluorescence. Up-regulation of MMP-2 and MMP-9 was found after IL-5, IL-20, and IL-28A stimulation in both cell types. Moreover, an EMSA assay showed that treatment with IL-5, IL-20, and IL-28A induced activation of the transcription factors NF-κB and AP-1 that regulate the MMP-9 promoter. Finally, activation of MAPK and Jak-Stat signaling was observed after the addition of IL-5, IL-20, and IL-28A to bladder cancer cells. This study suggests the presence of specific inflammatory cytokine (IL-5, IL-20, and IL-28A-mediated association in bladder cancer development. All 3 cytokines may be important new molecular targets for the modulation

  10. Copy Number Analysis of 24 Oncogenes: MDM4 Identified as a Putative Marker for Low Recurrence Risk in Non Muscle Invasive Bladder Cancer

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    Samanta Salvi

    2014-07-01

    Full Text Available Patients with non-muscle invasive bladder cancer (NMIBC generally have a high risk of relapsing locally after primary tumor resection. The search for new predictive markers of local recurrence thus represents an important goal for the management of this disease. We studied the copy number variations (CNVs of 24 oncogenes (MDM4, MYCN, ALK, PDGFRA, KIT, KDR, DHFR, EGFR, MET, SMO, FGFR1, MYC, ABL1, RET, CCND1, CCND2, CDK4, MDM2, AURKB, ERBB2, TOP2A, AURKA, AR and BRAF using multiplex ligation probe amplification technique to verify their role as predictive markers of recurrence. Formalin-fixed paraffin-embedded tissue samples from 43 patients who underwent transurethral resection of the bladder (TURB were used; 23 patients had relapsed and 20 were disease-free after 5 years. Amplification frequencies were analyzed for all genes and MDM4 was the only gene that showed significantly higher amplification in non recurrent patients than in recurrent ones (0.65 vs. 0.3; Fisher’s test p = 0.023. Recurrence-free survival analysis confirmed the predictive role of MDM4 (log-rank test p = 0.041. Our preliminary results indicate a putative role for the MDM4 gene in predicting local recurrence of bladder cancer. Confirmation of this hypothesis is needed in a larger cohort of NMIBC patients.

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

    Energy Technology Data Exchange (ETDEWEB)

    Isaka, Shigeo; Igarashi, Tatsuo; Ito, Haruo

    1983-10-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

  13. Updated 2016 EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer.

    Science.gov (United States)

    Alfred Witjes, J; Lebret, Thierry; Compérat, Eva M; Cowan, Nigel C; De Santis, Maria; Bruins, Harman Maxim; Hernández, Virginia; Espinós, Estefania Linares; Dunn, James; Rouanne, Mathieu; Neuzillet, Yann; Veskimäe, Erik; van der Heijden, Antoine G; Gakis, Georgios; Ribal, Maria J

    2017-03-01

    Invasive bladder cancer is a frequently occurring disease with a high mortality rate despite optimal treatment. The European Association of Urology (EAU) Muscle-invasive and Metastatic Bladder Cancer (MIBC) Guidelines are updated yearly and provides information to optimise diagnosis, treatment, and follow-up of this patient population. To provide a summary of the EAU guidelines for physicians and patients confronted with muscle-invasive and metastatic bladder cancer. An international multidisciplinary panel of bladder cancer experts reviewed and discussed the results of a comprehensive literature search of several databases covering all sections of the guidelines. The panel defined levels of evidence and grades of recommendation according to an established classification system. Epidemiology and aetiology of bladder cancer are discussed. The proper diagnostic pathway, including demands for pathology and imaging, is outlined. Several treatment options, including bladder-sparing treatments and combinations of treatment modalities (different forms of surgery, radiation therapy, and chemotherapy) are described. Sequencing of these modalities is discussed. Potential indications and contraindications, such as comorbidity, are related to treatment choice. There is a new paragraph on organ-sparing approaches, both in men and in women, and on minimal invasive surgery. Recommendations for chemotherapy in fit and unfit patients are provided including second-line options. Finally, a follow-up schedule is provided. The current summary of the EAU Muscle-invasive and Metastatic Bladder Cancer Guidelines provides an up-to-date overview of the available literature and evidence dealing with diagnosis, treatment, and follow-up of patients with metastatic and muscle-invasive bladder cancer. Bladder cancer is an important disease with a high mortality rate. These updated guidelines help clinicians refine the diagnosis and select the appropriate therapy and follow-up for patients with

  14. 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.

  15. 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

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

    Directory of Open Access Journals (Sweden)

    Douglas G Ward

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

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

    Science.gov (United States)

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

    2007-01-01

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

  18. Reduction of recurrence in non-muscle invasive bladder cancer using photodynamic diagnosis and immediate post-TUR-B chemoprophylaxis

    DEFF Research Database (Denmark)

    Risager, Malene Bøg

    2013-01-01

    (TUR-B), and one single instillation of 40 mg Mitomycin C (MMC) within 24 hours post-TUR-B were introduced at our institution by March 2008. For the study, patients were identified retrospectively using procedure codes for TUR-B and cystoscopy with biopsy and fulguration. Patients with muscle...

  19. 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

  20. Translating biology into clinic: new insights on prognostic and predictive biomarkers for urothelial bladder carcinoma

    OpenAIRE

    2013-01-01

    Tese de doutoramento em Ciências da Saúde Urothelial bladder carcinoma (UBC) represents a significant health problem, as a consequence of its heterogeneous natural history and clinical behavior. Most morbidity and mortality associated with UBC is caused by the muscle-invasive (MI) form of the disease, which represents about 20-30% of all newly diagnosed cases. Moreover, an important proportion of high risk non-muscle invasive (NMI) tumours relapse after transurethral resection and progress...

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

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    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

  2. Evaluation of tissue and urinary survivin expression in non-muscle-invasive bladder cancer

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    S. Sharaf

    2012-12-01

    Conclusion: Urinary survivin is a useful marker for non-invasive detection of non-muscle-invasive bladder cancer recurrence. Its detection is better using ELISA technique than WB and there is no correlation between its expression in tissue and urine.

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

    Directory of Open Access Journals (Sweden)

    Maurice M Garcia

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

  4. Invasive bladder cancer in the eighties: transurethral resection or cystectomy?

    Directory of Open Access Journals (Sweden)

    Oscar Rodriguez Faba

    2011-02-01

    Full Text Available PURPOSE: Describe morbidity and survival in patients older than 80 years with muscle invasive bladder cancer (MIBC treated with radical cystectomy (RC or transurethral resection (TUR in our institution. MATERIALS AND METHODS: We reviewed our database of all patients older than 80 years treated with RC and TUR for MIBC between 1993 and 2005 in our institution. Twenty-seven patients were submitted to RC, with mean age of 82 years and mean follow-up of 16.4 months. RC was carried out following diagnosis of previous MIBC in 14 cases (51.9%. The American Society of Anesthesiology (ASA score was III or IV in 23 patients (85.1%. Seventy-two patients with a mean age of 84 years and mean follow-up of 33 months, diagnosed with MIBC, were managed by means of TUR. The ASA score was III-IV in 64 (88.8% patients. RESULTS: Pathological stage of the RC specimen was pT3 in 18 cases (66.7%. Mean hospital stay was 16 days. Early complications were assessed in 8 patients (29.6%, with an overall survival (OS of 42.94%, and cancer-specific survival (CSS of 60.54%. In patients submitted to TUR, clinical stage was T2 in 36 cases (50%. The mean hospital stay was 7 days, with a readmission rate (RR of 87.5%. OS and CSS was less than 20%. CONCLUSIONS: RC in octogenarian patients is a safe procedure, with complication and survival rates comparable to RC series in general population. Transurethral resection (TUR for patients with MIBC within this age range is a much less morbid procedure, but disease specific survival is lower.

  5. 经尿道膀胱肿瘤电切术与绿激光治疗非肌层侵润性膀胱癌的临床效果及预后分析%The Clinical Effect and Prognostic Analysis of Transurethral Resection of Bladder Tumor and Green Laser in the Treatment of Non Muscle Invasive Bladder Cancer

    Institute of Scientific and Technical Information of China (English)

    柳坤

    2015-01-01

    目的:探究与分析经尿道膀胱肿瘤电切术和绿激光治疗非肌层浸润性膀胱癌的临床效果及预后。方法选自我院2014年8月~2015年5月收治的非浸润性膀胱癌患者86例,按随机数法分为电切组和激光组,分别给予经尿道电切术和绿激光治疗,观察两组患者手术中的情况以及手术后的情况,将结果进行对比分析。结果激光组患者在术中及术后的不良反应低于电切组,P<0.05,差异具有统计学意义。结论经尿道膀胱肿瘤电切术和绿激光治疗法均能有效治疗非肌层浸润性膀胱癌,绿激光治疗更为安全高效。%Objective To explore and analyze the clinical efficacy and prognosis for patients with non-muscle invasive bladder cancer treated with transurethral bladder tumor resection and green laser. Methods 86 cases of non invasive bladder cancer patients were selected from August 2014 to May 2015 that treated at our hospital. All the patients were divided into two groups, the resection group and the laser group, separately treated with transurethral resection and green laser. The intraoperative and postoperative condition of patients would be analyzed and compared between groups. Results In the laser group, the adverse events of intraoperative and postoperative patients was significantly lower than that of the resection group, P<0.05, compared with statistical significance. Conclusion Transurethral resection of bladder tumor and green laser therapy can effectively treat non-muscle invasive bladder cancer. The green laser treatment is worthy of further research and extension in the clinic with the advantage of more safe and effective..

  6. 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...

  7. Potential therapeutic strategies for non - muscle invasive bladder cancer based on association of intravesical immunotherapy with p - mapa and systemic administration of cisplatin and doxorubicin.

    Science.gov (United States)

    Dias, Queila Cristina; Nunes, Iseu da Silva; Garcia, Patrick Vianna; Favaro, Wagner Jose

    2016-01-01

    The present study describes the histopathological and molecular effects of P-MAPA (Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride) intravesical immunotherapy combined with systemic doxorubicin or cisplatin for treatment of non-muscle invasive bladder cancer (NMIBC) in an appropriate animal model. Our results showed an undifferentiated tumor, characterizing a tumor invading mucosa or submucosa of the bladder wall (pT1) and papillary carcinoma in situ (pTa) in the Cancer group. The histopathological changes were similar between the combined treatment with intravesical P-MAPA plus systemic Cisplatin and P-MAPA immunotherapy alone, showing decrease of urothelial neoplastic lesions progression and histopathological recovery in 80% of the animals. The animals treated systemically with cisplatin or doxorubicin singly, showed 100% of malignant lesions in the urinary bladder. Furthemore, the combined treatment with P-MAPA and Doxorubicin showed no decrease of urothelial neoplastic lesions progression and histopathological recovery. Furthermore, Akt, PI3K, NF-kB and VEGF protein levels were significantly lower in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments than other groups. In contrast, PTEN protein levels were significantly higher in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments. Thus, it could be concluded that combination of intravesical P-MAPA immunotherapy and systemic cisplatin in the NMIBC animal model was effective, well tolerated and showed no apparent signs of antagonism between the drugs. In addition, intravesical P-MAPA immunotherapy may be considered as a valuable option for treatment of BCG unresponsive patients that unmet the criteria for early cystectomy.

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

    Science.gov (United States)

    Smith, Sean G; Zaharoff, David A

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-03-01

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

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

    Science.gov (United States)

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

    2012-07-01

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

  11. Hospitalization for transurethral bladder resection reduces quality of life in Danish patients with non-muscle-invasive bladder tumour

    DEFF Research Database (Denmark)

    Mogensen, Karin; Christensen, Karl B.; Vrang, Marie-Louise;

    2016-01-01

    Objective The aim of the study was to evaluate the impact of transurethral resection of bladder tumour (TURBT) on patients' quality of life (QoL) and to validate a tool to quantify problems associated with TURBT in a Danish population. Materials and methods A prospective study was carried out using...... a combination of questionnaires and interviews. The study included 165 consecutive patients undergoing a TURBT owing to non-muscle-invasive bladder cancer (NMIBC) from 1 May 2011 to 30 April 2012. Seven patients were selected for interviews. The Danish translation of the QLQ-NMIBC24 Quality of Life...... Questionnaire for NMIBC, from the European Organisation for Research and Treatment of Cancer (EORTC), was used. The interviews were semi-structured. The reliability of the subscales quantifying QoL as defined by the EORTC was tested by computing Cronbach's coefficient alpha and confirmatory factor analysis...

  12. Successful outcome of placenta previa percreta with bladder invasion

    Directory of Open Access Journals (Sweden)

    Syeda Sayeeda

    2017-06-01

    Full Text Available A 41 year old multiparous lady, with previous history of one cesarean section presented at her 24 weeks of gestation with frank hematuria. The case was diagnosed as placenta previa percreta with the bladder involvement by ultrasound doppler and confirmed by MR urogram. So, peripartum hysterectomy was planned. On opening of the abdomen, a hugely distended bladder was found, which when retracted engorged blood vessels were found over the lower segment of uterus. Baby was delivered by giving a transverse incision in the upper segment. By keeping placenta in situ, total abdominal hysterectomy was done with quick successive clamping. Severe per-operative bleeding was occurred. Bladder irrigation started following total abdominal hysterectomy. Continuous small clots were coming out through catheter. A large old blood clot was removed by cystostomy done by an urologist. A sprouting vessel and a linear injury were noticed at the base of the bladder. The vessel was ligated and the injury was repaired. After proper hemostasis, the abdomen was closed in layers. The patient was shifted to ICU. Patient developed complications like MI, watery diarrhoea, low grade fever which was managed accordingly. She was discharged healthy on her 19th post-operative day.

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

    Science.gov (United States)

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

    2017-02-28

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

  14. 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....

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  16. The updated EAU guidelines on muscle-invasive and metastatic bladder cancer.

    NARCIS (Netherlands)

    Stenzl, A.; Cowan, N.C.; Santis, M. de; Jakse, G.; Kuczyk, M.A.; Merseburger, A.S.; Ribal, M.J.; Sherif, A.; Witjes, J.A.

    2009-01-01

    CONTEXT: New data regarding diagnosis and treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. OBJECTIVE: To review the new EAU guidelines for MiM-BC. EVIDENCE ACQUISITION: A

  17. Treatment Options Available for Bacillus Calmette-Guerin Failure in Non-muscle-invasive Bladder Cancer

    NARCIS (Netherlands)

    Yates, D.R.; Brausi, M.A.; Catto, J.W.; Dalbagni, G.; Roupret, M.; Shariat, S.F.; Sylvester, R.J.; Witjes, J.A.; Zlotta, A.R.; Palou-Redorta, J.

    2012-01-01

    CONTEXT: Intravesical bacillus Calmette-Guerin (BCG) is a standard conservative treatment for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Many patients will experience recurrence or progression following BCG and are termed BCG failures. OBJECTIVE: To summarise the current tre

  18. Bladder Cancer Immunotherapy: BCG and Beyond

    Directory of Open Access Journals (Sweden)

    Eric J. Askeland

    2012-01-01

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

  19. Bladder Cancer Immunotherapy: BCG and Beyond.

    Science.gov (United States)

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

    2012-01-01

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

  20. Linearized texture of three-dimensional extracellular matrix is mandatory for bladder cancer cell invasion

    Science.gov (United States)

    Alfano, Massimo; Nebuloni, Manuela; Allevi, Raffaele; Zerbi, Pietro; Longhi, Erika; Lucianò, Roberta; Locatelli, Irene; Pecoraro, Angela; Indrieri, Marco; Speziali, Chantal; Doglioni, Claudio; Milani, Paolo; Montorsi, Francesco; Salonia, Andrea

    2016-01-01

    In the fields of biomaterials and tissue engineering simulating the native microenvironment is of utmost importance. As a major component of the microenvironment, the extracellular matrix (ECM) contributes to tissue homeostasis, whereas modifications of native features are associated with pathological conditions. Furthermore, three-dimensional (3D) geometry is an important feature of synthetic scaffolds favoring cell stemness, maintenance and differentiation. We analyzed the 3D structure, geometrical measurements and anisotropy of the ECM isolated from (i) human bladder mucosa (basal lamina and lamina propria) and muscularis propria; and, (ii) bladder carcinoma (BC). Next, binding and invasion of bladder metastatic cell line was observed on synthetic scaffold recapitulating anisotropy of tumoral ECM, but not on scaffold with disorganized texture typical of non-neoplastic lamina propria. This study provided information regarding the ultrastructure and geometry of healthy human bladder and BC ECMs. Likewise, using synthetic scaffolds we identified linearization of the texture as a mandatory feature for BC cell invasion. Integrating microstructure and geometry with biochemical and mechanical factors could support the development of an innovative synthetic bladder substitute or a tumoral scaffold predictive of chemotherapy outcomes. PMID:27779205

  1. [Effectiveness of a program of early instillation single chemotherapy in patients with bladder cancer].

    Science.gov (United States)

    Beardo Villar, P; Pérez Pérez, A B; Castro Dorantes, M J; Jiménez Delgado, S J; Alamillos Ortega, P; Gavira Moreno, R

    2016-01-01

    To determine the effectiveness of early intravesical chemotherapy intervention for patients with non-muscle invasive bladder cancer, before and after a training and inter-professional communication plan. Non-experimental prospective longitudinal study of a cohort of 349 patients with endoscopic diagnosis of a non-muscle invasive bladder tumour in Northern Area Health Management of Cadiz between 2010 and 2013 and amenable to postoperative treatment with mitomycin C. The mean rate of patients included in the program was 53.9%. The inclusion rate rose by 79.3% at 3 years. The absolute risk reduction of recurrence for patients receiving treatment is 18.1% (95% CI; 8.81% - 27.48%, pplan for evaluation and dissemination of results has achieved a good level of adherence among professionals, obtaining the expected impact on the reduction of early recurrence of non-muscle invasive bladder cancer. Copyright © 2015 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Systemic chemotherapy in muscle invasive and metastatic bladder cancer: present and future.

    Science.gov (United States)

    Del Bene, Gabriella; Sternberg, Cora N

    2017-08-01

    Bladder cancer is the most frequent among the urothelial tumors, and it is responsible for about 2% of all cancer mortality worldwide. The mainstay of chemotherapy treatment, both for muscle-invasive and metastatic disease, is cisplatin-based regimens. In recent years, ground-breaking results have been achieved with immunotherapy, which have led to important breakthroughs in the bladder cancer treatment scenario, with the approval of several new agents. New insights derive from a greater characterization of the tumor genome, which could lead to developing new therapies, more personalized, in the near future.

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

    Science.gov (United States)

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

    2014-01-01

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

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    T. A. Sveklina

    2014-08-01

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

  6. Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth

    Directory of Open Access Journals (Sweden)

    Claudia Ceci

    2016-11-01

    Full Text Available Ellagic acid (EA is a polyphenolic compound that can be found as a naturally occurring hydrolysis product of ellagitannins in pomegranates, berries, grapes, green tea and nuts. Previous studies have reported the antitumor properties of EA mainly using in vitro models. No data are available about EA influence on bladder cancer cell invasion of the extracellular matrix triggered by vascular endothelial growth factor-A (VEGF-A, an angiogenic factor associated with disease progression and recurrence, and tumor growth in vivo. In this study, we have investigated EA activity against four different human bladder cancer cell lines (i.e., T24, UM-UC-3, 5637 and HT-1376 by in vitro proliferation tests (measuring metabolic and foci forming activity, invasion and chemotactic assays in response to VEGF-A and in vivo preclinical models in nude mice. Results indicate that EA exerts anti-proliferative effects as a single agent and enhances the antitumor activity of mitomycin C, which is commonly used for the treatment of bladder cancer. EA also inhibits tumor invasion and chemotaxis, specifically induced by VEGF-A, and reduces VEGFR-2 expression. Moreover, EA down-regulates the expression of programmed cell death ligand 1 (PD-L1, an immune checkpoint involved in immune escape. EA in vitro activity was confirmed by the results of in vivo studies showing a significant reduction of the growth rate, infiltrative behavior and tumor-associated angiogenesis of human bladder cancer xenografts. In conclusion, these results suggest that EA may have a potential role as an adjunct therapy for bladder cancer.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-02-01

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

  8. Effects of neoadjuvant chemotherapy on pathological parameters and survival in patients undergoing radical cystectomy for muscle-invasive bladder cancer

    OpenAIRE

    ÇAĞLAYAN, Alper; Akbulut, Ziya; Atmaca, Ali Fuat; Altinova,Serkan; KILIÇ, Metin; Balbay, Mevlana Derya

    2012-01-01

    Aim: To evaluate the effect of neoadjuvant chemotherapy on tumor pathology and patient survival in patients with muscle-invasive bladder cancer undergoing radical cystectomy. Neoadjuvant chemotherapy is believed to prevent micrometastasis and provide pathological downstaging. Materials and methods: Between June 2004 and March 2009, 74 patients with muscle-invasive bladder cancer were treated with radical cystectomy. Patients fit to receive chemotherapy were administered systemic chemotherapy...

  9. XIAP as a prognostic marker of early recurrence of nonmuscular invasive bladder cancer

    Institute of Scientific and Technical Information of China (English)

    LI Ming; SONG Tao; YIN Zhen-fei; NA Yan-qun

    2007-01-01

    Background Dysregulation of apoptosis has been implicated not only in carcinogenesis and tumor progression but also in tumor recurrence. We investigated whether the expression of X-linked inhibitor of apoptosis (XIAP) might predict early recurrence in patients with non-muscular invasive bladder cancer.Methods The cohort comprised 176 consecutive patients with primary superficial bladder cancer treated with transurethral resection. Immunohistochemical staining using the standard avidin-biotin-peroxidase technique and RT-PCR were used to detect XIAP protein and mRNA expressions in cancer tissues. The relationship between XIAP expression and clinicopathological characteristics, cancer recurrence were analyzed.Results XIAP expression was observed in 108 cases (61.4%) and no expression in 68. There was no correlation between XIAP expression rate and the tumor pathological grade, but was an apparent trend toward the increased XIAP levels from well (G1) to poor (G3) differentiated cancer. Eighty-two (46.6%) patients experienced tumor recurrence at a mean of 28.6 months of the follow-up; 66 of them expressed XIAP (61.1%) and 16 were XIAP negative (23.5%). Twelve patients presented with invasive disease at the time of relapse and all of them expressed XIAP. Patients without XIAP expression or with low tumor grades had significantly higher recurrence-free survival than those with XIAP expression(log rank test P=0.0015) or high tumor grades (log rank test P<0.001). Multivariate analysis revealed that XIAP expression, tumor grade, and tumor number were independent predictors for the recurrence of non-muscular invasive bladder cancer (P=-0.004, 0.016, and 0.043, respectively).Conclusions XIAP may be considered as a new independent prognostic marker for early recurrence of non-muscular invasive bladder cancer.

  10. Afatinib inhibits proliferation and invasion and promotes apoptosis of the T24 bladder cancer cell line.

    Science.gov (United States)

    Tang, Yunhua; Zhang, Xiangyang; Qi, Fan; Chen, Mingfeng; Li, Yuan; Liu, Longfei; He, Wei; Li, Zhuo; Zu, Xiongbing

    2015-05-01

    Afatinib is a highly selective, irreversible inhibitor of the epidermal growth factor receptor (EGFR) and human EGFR 2 (HER-2). Although preclinical and clinical studies have indicated that afatinib has antitumor activity and clinical efficacy in non-small cell lung carcinoma, head and neck squamous cell carcinoma and breast cancer, there are few studies investigating its inhibitory effect on human bladder carcinoma cells. In this study, the antitumor effect of afatinib was investigated on the T24 bladder cancer cell line. The T24 bladder cancer cell line was treated with afatinib at various concentrations (0, 1, 5, 10 and 20 µmol/l). MTT assay was used to estimate the proliferation of the T24 cells; flow cytometric analysis was used to estimate the effect of afatinib on T24 cell apoptosis; cell invasion ability was assessed by a Transwell invasion assay; and western blot analysis was used to detect the expression of Bcl-2, Bax, Akt, extracellular-signal-regulated kinase (ERK)1/2, matrix metalloproteinase (MMP)-2 and MMP-9. The MTT assay demonstrated that afatinib inhibited the proliferation of T24 cells in a dose- and time-dependent manner. Flow cytometric analysis revealed that the cell apoptosis rate increased as the concentration of afatinib increased. The cell invasion assay indicated that afatinib treatment significantly inhibited the invasive behavior of T24 cells in a dose-dependent manner. Western blot analysis showed that with increasing afatinib concentrations, Bcl-2, phosphorylated (p)-ERK1/2, p-Akt, MMP-2 and MMP-9 expression levels were significantly decreased, whereas total (t)-ERK1/2 and t-Akt expression levels remained basically unchanged, and Bax expression levels were greatly increased. The results indicate that afatinib inhibits the proliferation and invasion of T24 cells in vitro and induces the apoptosis of these cells by inhibiting the EGFR signaling network.

  11. 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.)

  12. Mechanisms by Which Interleukin-6 Attenuates Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Ke-Hung Tsui

    2013-01-01

    Full Text Available Interleukin-6, a multifunctional cytokine, contributes to tumor cell proliferation and differentiation. However, the biological mechanisms that are affected by the expression of interleukin-6 in bladder cancer cells remain unclear. We evaluated the effects of interleukin-6 expression in human bladder carcinoma cells in vitro and in vivo. The results of interleukin-6-knockdown experiments in T24 cells and interleukin-6-overexpression experiments in HT1376 cells revealed that interleukin-6 reduced cell proliferation, migration, and invasion in vitro. Xenograft animal studies indicated that the overexpression of interleukin-6 downregulated tumorigenesis of bladder cells and that interleukin-6 knockdown reversed this effect. The results of RT-PCR, immunoblotting, and reporter assays indicated that the overexpression of interleukin-6 upregulated the expression of the mammary serine protease inhibitor (MASPIN, N-myc downstream gene 1 (NDRG1, and KAI1 proteins in HT1376 cells and that interleukin-6 knockdown reduced the expression of these proteins in T24 cells. In addition, results of immunoblotting assays revealed that interleukin-6 modulated epithelial-mesenchymal transitions by upregulating the expression of the E-cadherin, while downregulation N-cadherin and vimentin proteins. Our results suggest that the effects of interleukin-6 on the regulation of epithelial-mesenchymal transitions and the expressions of the MASPIN, NDRG1, and KAI1 genes attribute to the modulation of tumorigenesis in human bladder carcinoma cells.

  13. Inhibiting cell migration and cell invasion by silencing the transcription factor ETS-1 in human bladder cancer.

    Science.gov (United States)

    Liu, Li; Liu, Yuchen; Zhang, Xintao; Chen, Mingwei; Wu, Hanwei; Lin, Muqi; Zhan, Yonghao; Zhuang, Chengle; Lin, Junhao; Li, Jianfa; Xu, Wen; Fu, Xing; Zhang, Qiaoxia; Sun, Xiaojuan; Zhao, Guoping; Huang, Weiren

    2016-05-03

    As one of the members of the ETS gene family, the transcription factor v-ets avian erythroblastosis virus E26 oncogene homolog 1 (ETS-1) plays key role in the regulation of physiological processes in normal cells and tumors. In this study, we aimed to investigate the relationship between the transcription factor ETS-1 and malignant phenotypes of bladder cancer. We demonstrated that ETS-1 was up-regulated in human bladder cancer tissue compared to paired normal bladder tissue. In order to evaluate the functional role of ETS-1 in human bladder cancer, vectors expressing ETS-1 shRNA and ETS-1 protein were constructed in vitro and transfected into the human bladder cancer T24 and 5637 cells. Our results showed that the transcription factor ETS-1 could promote cell migration and cell invasion in human bladder cancer, without affecting cell proliferation and apoptosis. In conclusion, ETS-1 plays oncogenic roles through inducing cell migration and invasion in human bladder cancer, and it can be used as a therapeutic target for treating human bladder cancer.

  14. Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises.

    Science.gov (United States)

    Aragon-Ching, Jeanny B; Trump, Donald L

    2016-09-01

    Bladder urothelial cancers remain an important urologic cancer with limited treatment options in the locally advanced and metastatic setting. While neoadjuvant chemotherapy for locally advanced muscle-invasive cancers has shown overall survival benefit, clinical uptake in practice have lagged behind. Controversies surrounding adjuvant chemotherapy use are also ongoing. Systemic therapies for metastatic bladder cancer have largely used platinum-based therapies without effective standard second-line therapy options for those who fail, although vinflunine is approved in Europe as a second-line therapy based on a Phase III trial, and most recently, atezolizumab, a checkpoint inhibitor, was approved by the US FDA. Given increasing recognition of mutational signatures expressed in urothelial carcinomas, several promising agents with use of VEGF-targeted therapies, HER2-directed agents and immunotherapies with PD-1/PD-L1 antibodies in various settings are discussed herein.

  15. EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines.

    Science.gov (United States)

    Witjes, J Alfred; Compérat, Eva; Cowan, Nigel C; De Santis, Maria; Gakis, Georgios; Lebret, Thierry; Ribal, Maria J; Van der Heijden, Antoine G; Sherif, Amir

    2014-04-01

    The European Association of Urology (EAU) guidelines panel on Muscle-invasive and Metastatic bladder cancer (BCa) updates its guidelines yearly. This updated summary provides a synthesis of the 2013 guidelines document, with emphasis on the latest developments. To provide graded recommendations on the diagnosis and treatment of patients with muscle-invasive BCa (MIBC), linked to a level of evidence. For each section of the guidelines, comprehensive literature searches covering the past 10 yr in several databases were conducted, scanned, reviewed, and discussed both within the panel and with external experts. The final results are reflected in the recommendations provided. Smoking and work-related carcinogens remain the most important risk factors for BCa. Computed tomography (CT) and magnetic resonance imaging can be used for staging, although CT is preferred for pulmonary evaluation. Open radical cystectomy with an extended lymph node dissection (LND) remains the treatment of choice for treatment failures in non-MIBC and T2-T4aN0M0 BCa. For well-informed, well-selected, and compliant patients, however, multimodality treatment could be offered as an alternative, especially if cystectomy is not an option. Comorbidity, not age, should be used when deciding on radical cystectomy. Patients should be encouraged to actively participate in the decision-making process, and a continent urinary diversion should be offered to all patients unless there are specific contraindications. For fit patients, cisplatinum-based neoadjuvant chemotherapy should always be discussed, since it improves overall survival. For patients with metastatic disease, cisplatin-containing combination chemotherapy is recommended. For unfit patients, carboplatin combination chemotherapy or single agents can be used. This 2013 EAU Muscle-invasive and Metastatic BCa guidelines updated summary aims to increase the quality of care and outcome for patients with muscle-invasive or metastatic BCa. In this

  16. [Treatment of muscle-invasive and metastatic bladder cancer: update of the EAU guidelines].

    Science.gov (United States)

    Stenzl, A; Cowan, N C; De Santis, M; Kuczyk, M A; Merseburger, A S; Ribal, M J; Sherif, A; Witjes, J A

    2012-09-01

    New data regarding treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. To review the new EAU guidelines for MiM-BC with a specific focus on treatment. New literature published since the last update of the EAU guidelines in 2008 was obtained from Medline, the Cochrane Database of Systematic Reviews, and reference lists in publications and review articles and comprehensively screened by a group of urologists, oncologists, and a radiologist appointed by the EAU Guidelines Office. Previous recommendations based on the older literature on this subject were also taken into account. Levels of evidence (LEs) and grades of recommendations (GRs) were added based on a system modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. Current data demonstrate that neoadjuvant chemotherapy in conjunction with radical cystectomy (RC) is recommended in certain constellations of MiM-BC. RC remains the basic treatment of choice in localised invasive disease for both sexes. An attempt has been made to define the extent of surgery under standard conditions in both sexes. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. In contrast to neoadjuvant chemotherapy, current advice recommends the use of adjuvant chemotherapy only within clinical trials. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for medical or personal reasons. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin remains cisplatin-containing combination chemotherapy. With the advent of vinflunine, second-line chemotherapy has become available. In the treatment of localised

  17. EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016.

    Science.gov (United States)

    Babjuk, Marko; Böhle, Andreas; Burger, Maximilian; Capoun, Otakar; Cohen, Daniel; Compérat, Eva M; Hernández, Virginia; Kaasinen, Eero; Palou, Joan; Rouprêt, Morgan; van Rhijn, Bas W G; Shariat, Shahrokh F; Soukup, Viktor; Sylvester, Richard J; Zigeuner, Richard

    2017-03-01

    The European Association of Urology (EAU) panel on Non-muscle-invasive Bladder Cancer (NMIBC) released an updated version of the guidelines on Non-muscle-invasive Bladder Cancer. To present the 2016 EAU guidelines on NMIBC. A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines published between April 1, 2014, and May 31, 2015, was performed. Databases covered by the search included Medline, Embase, and the Cochrane Libraries. Previous guidelines were updated, and levels of evidence and grades of recommendation were assigned. Tumours staged as TaT1 or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection of the bladder (TURB) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TURB is essential for the patient's prognosis. If the initial resection is incomplete, there is no muscle in the specimen, or a high-grade or T1 tumour is detected, a second TURB should be performed within 2-6 wk. The risks of both recurrence and progression may be estimated for individual patients using the European Organisation for Research and Treatment of Cancer (EORTC) scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups is pivotal to recommending adjuvant treatment. For patients with a low-risk tumour and intermediate-risk patients at a lower risk of recurrence, one immediate instillation of chemotherapy is recommended. Patients with an intermediate-risk tumour should receive 1 yr of full-dose bacillus Calmette-Guérin (BCG) intravesical immunotherapy or instillations of chemotherapy for a maximum of 1 yr. In patients with high-risk tumours, full-dose intravesical BCG for 1-3 yr is indicated. In patients at highest risk of tumour progression, immediate radical cystectomy (RC) should be considered. RC is recommended in BCG-refractory tumours. The long version of

  18. Treatment of muscle-invasive and metastatic bladder cancer: update of the EAU guidelines.

    Science.gov (United States)

    Stenzl, Arnulf; Cowan, Nigel C; De Santis, Maria; Kuczyk, Markus A; Merseburger, Axel S; Ribal, Maria José; Sherif, Amir; Witjes, J Alfred

    2011-06-01

    New data regarding treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. To review the new EAU guidelines for MiM-BC with a specific focus on treatment. New literature published since the last update of the EAU guidelines in 2008 was obtained from Medline, the Cochrane Database of Systematic Reviews, and reference lists in publications and review articles and comprehensively screened by a group of urologists, oncologists, and a radiologist appointed by the EAU Guidelines Office. Previous recommendations based on the older literature on this subject were also taken into account. Levels of evidence (LEs) and grades of recommendations (GRs) were added based on a system modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. Current data demonstrate that neoadjuvant chemotherapy in conjunction with radical cystectomy (RC) is recommended in certain constellations of MiM-BC. RC remains the basic treatment of choice in localised invasive disease for both sexes. An attempt has been made to define the extent of surgery under standard conditions in both sexes. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. In contrast to neoadjuvant chemotherapy, current advice recommends the use of adjuvant chemotherapy only within clinical trials. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for medical or personal reasons. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin remains cisplatin-containing combination chemotherapy. With the advent of vinflunine, second-line chemotherapy has become available. In the treatment of localised

  19. A Non-Invasive Ultrasonic Urinary Bladder Internal Pressure Monitoring Technique: Its Theoretical Foundation and Feasibility Test

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Min Joo; Kang, Gwan Suk [Jeju National University, Jeju (Korea, Republic of); Lee, Kang Il [Department of Physics, Kangwon National University, Chuncheon (Korea, Republic of)

    2012-10-15

    A new approach was proposed in this article, named, a non-invasive ultrasonic method to monitor the urinary bladder internal pressure which can resolve the shortcomings of the existing methods. The proposed method makes use of acoustic cavitation. It is based on a physical phenomenon that an extracorporeal high intensity focused ultrasonic pulse generates bubbles inside the urinary bladder and the dynamic properties of the bubbles are related to the urinary bladder internal pressure. The article presents the theoretical foundation for the proposed technique and verifies its feasibility with preliminary experimental data. The suggested ultrasonic urinary bladder internal pressure monitoring method is non-invasive and can be used any time regardless of sex and age.

  20. Differential Proteomic Analysis of Nuclear Matrix in Muscle-Invasive Bladder Cancer: Potential to Improve Diagnosis and Prognosis

    Directory of Open Access Journals (Sweden)

    Paola Barboro

    2008-01-01

    Full Text Available Introduction: Although several molecular markers for bladder cancer have been identified, at present little information on prognostic biomarkers is available in the literature. Prognostication of this tumor is largely based on clinicopathological characteristics. Our aim was to identify nuclear matrix (NM proteins that might serve to better characterize the phenotype of the invasive bladder cancer and to investigate their diagnostic and prognostic roles.

  1. Novel intravesical therapies for non-muscle-invasive bladder cancer refractory to BCG.

    Science.gov (United States)

    Barlow, Lamont J; Seager, Catherine M; Benson, Mitchell C; McKiernan, James M

    2010-01-01

    The definitive treatment for patients with non-muscle-invasive bladder cancer (NMIBC) who fail to respond to intravesical BCG is cystectomy. When a patient is deemed BCG-refractory and cannot or will not undergo cystectomy, alternative intravesical therapy may be the most effective way to minimize recurrence and progression. A number of immunotherapeutic and chemotherapeutic agents have been given intravesically over the years, and several recently and currently investigated novel agents appear to be particularly promising for the management of BCG-refractory NMIBC. The most effective treatments in the future will likely utilize targeted therapies based on the underlying genetic mutations associated with each individual diagnosis of NMIBC.

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

    Science.gov (United States)

    Balar, Arjun V; Milowsky, Matthew I

    2015-05-01

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

  3. Ginkgolide B Inhibits Human Bladder Cancer Cell Migration and Invasion Through MicroRNA-223-3p

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    Yi Zhi

    2016-10-01

    Full Text Available Background/Aims: Ginkgolide B (GB is currently used as an anticancer drug for treatment of some malignant cancers. However, whether it may have therapeutic effects on bladder cancer remains unknown. Here, we studied the effects of GB on bladder cancer cells. Methods: Bladder cells were treated with different doses of GB, and the effects on ZEB1 and microRNA-223-3p (miR-223-3p were analyzed by RT-qPCR and/or Western blot. Prediction of a regulatory relationship between miR-93 and 3'-UTR of Beclin-1 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Results: We found that GB dose-dependently decreased ZEB1 protein, but not mRNA, in bladder cancer cells, resulting in suppression of cell invasion. Moreover, in bladder cancer cells, GB dose-dependently decreased the levels of miR-223-3p, which suppressed the protein translation of ZEB1 through binding to 3'-UTR of ZEB1 mRNA. Overexpression of miR-223-3p decreased ZEB1 protein, while depletion of miR-223-3p increased ZEB1 protein in bladder cancer cells. Conclusion: GB inhibits bladder cancer cell invasiveness through suppressing ZEB1 protein translation via upregulating miR-223-3p.

  4. Human milk oligosaccharides protect bladder epithelial cells against uropathogenic Escherichia coli invasion and cytotoxicity.

    Science.gov (United States)

    Lin, Ann E; Autran, Chloe A; Espanola, Sophia D; Bode, Lars; Nizet, Victor

    2014-02-01

    The invasive pathogen uropathogenic Escherichia coli (UPEC) is the primary cause of urinary tract infections (UTIs). Recurrent infection that can progress to life-threatening renal failure has remained as a serious global health concern in infants. UPEC adheres to and invades bladder epithelial cells to establish infection. Studies have detected the presence of human milk oligosaccharides (HMOs) in urine of breast-fed, but not formula-fed, neonates. We investigated the mechanisms HMOs deploy to elicit protection in human bladder epithelial cells infected with UPEC CFT073, a prototypic urosepsis-associated strain. We found a significant reduction in UPEC internalization into HMO-pretreated epithelial cells without observing any significant effect in UPEC binding to these cells. This event coincides with a rapid decrease in host cell cytotoxicity, recognized by LIVE/DEAD staining and cell detachment, but independent of caspase-mediated or mitochondrial-mediated programmed cell death pathways. Further investigation revealed HMOs, and particularly the sialic acid-containing fraction, reduced UPEC-mediated MAPK and NF-κB activation. Collectively, our results indicate that HMOs can protect bladder epithelial cells from deleterious cytotoxic and proinflammatory effects of UPEC infection, and may be one contributing mechanism underlying the epidemiological evidence of reduced UTI incidence in breast-fed infants.

  5. Feasibility of organ preservation in muscle-invasive transitional cell carcinoma bladder: A single institutional approach

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    Chhaya Roy

    2015-01-01

    Full Text Available Background: Trimodality treatment initial transurethral resection of the bladder tumor [TURBT] followed by concurrent chemotherapy and radiation and organ preservation have been gradually replacing the radical cystectomy in muscle-invasive transitional cell carcinoma (TCC of bladder. Aims: The aims of this study is to determine the clinical effectiveness, safety and protocol completion rate of trimodality treatment in muscle-invasive TCC of the bladder. Settings and Design: Prospective randomized and open-labeled study. Subjects and Methods: Patients with TCC of bladder, American Joint Committee on Cancer tumor node metastasis (TNM Bladder Cancer Staging (2002 T2-3, N0, M0. Were underwent TURBT followed by three cycles of neoadjuvant chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin regimen. The patients were then randomized to receive either concurrent cisplatin 75 mg/m 2 in week 1 and 4 (arm-A or no cisplatin (arm-B along with external beam radiation therapy (EBRT 45 Gy, in 25 fractions over 5 weeks. 4 weeks after completion of the initial phase of treatment, all patients were re-evaluated with TURBT. Those with complete remission (CR received additional 15 Gy of EBRT in 8 fractions, while patients with residual disease were recommended for immediate radical cystectomy. All the patients of arm-B received boost dose of 15 Gy of EBRT. Statistical Analysis Used: The major statistical endpoints of this study were the CR rate at 8 weeks post-concurrent chemoradiotherapy (CCRT and only radiotherapy. Statistical significance was accepted at the P < 0.05 (two-sided level. Statistical analysis was performed entirely using the Statistical Package for the Social Sciences for Windows, version 17 (SPSS Inc., Chicago, IL, U.S.A.. Results: 8 weeks after completion of treatment 13/16 (81% patients were in CR in CCRT arm (arm-A compare to 6/15 (40% patients receiving radiation only (arm-B. Conclusions: Patients, after TURBT receiving CCRT

  6. The updated EAU guidelines on muscle-invasive and metastatic bladder cancer.

    Science.gov (United States)

    Stenzl, Arnulf; Cowan, Nigel C; De Santis, Maria; Jakse, Gerhard; Kuczyk, Marcus A; Merseburger, Axel S; Ribal, Maria José; Sherif, Amir; Witjes, J Alfred

    2009-04-01

    New data regarding diagnosis and treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. To review the new EAU guidelines for MiM-BC. A comprehensive workup of the literature obtained from Medline, the Cochrane central register of systematic reviews, and reference lists in publications and review articles was developed and screened by a group of urologists, oncologists, and radiologist appointed by the EAU Guideline Committee. Previous recommendations based on the older literature on this subject were taken into account. Levels of evidence and grade of guideline recommendations were added, modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. The diagnosis of muscle-invasive bladder cancer (BCa) is made by transurethral resection (TUR) and following histopathologic evaluation. Patients with confirmed muscle-invasive BCa should be staged by computed tomography (CT) scans of the chest, abdomen, and pelvis, if available. Adjuvant chemotherapy is currently only advised within clinical trials. Radical cystectomy (RC) is the treatment of choice for both sexes, and lymph node dissection should be an integral part of cystectomy. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for clinical or personal reasons. An appropriate schedule for disease monitoring should be based on (1) natural timing of recurrence, (2) probability of disease recurrence, (3) functional deterioration at particular sites, and (4) consideration of treatment of a recurrence. In metastatic disease, the first-line treatment for patients fit enough to

  7. MiR-200c promotes bladder cancer cell migration and invasion by directly targeting RECK

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    Cheng Y

    2016-08-01

    Full Text Available Yidong Cheng,* Xiaolei Zhang,* Peng Li,* Chengdi Yang, Jinyuan Tang, Xiaheng Deng, Xiao Yang, Jun Tao, Qiang Lu, Pengchao Li Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: Increasing evidence suggests that the dysregulation of certain microRNAs plays an important role in tumorigenesis and metastasis. MiR-200c exhibits a disordered expression in many tumors and presents dual roles in bladder cancer (BC. Therefore, the definite role of miR-200c in BC needs to be investigated further.Materials and methods: Quantitative reverse transcription polymerase chain reaction was used to assess miR-200c expression. Cell invasion and migration were evaluated using wound healing and transwell assays. The luciferase reporter assay was used to identify the direct target of miR-200c. The expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK in BC tissues and adjacent nontumor tissues, as well as in BC cell lines, was detected through quantitative reverse transcription polymerase chain reaction, Western blot assay, and immunohistochemistry.Results: The miR-200c expression was significantly upregulated in the BC tissues compared with the adjacent nontumor tissues. The downregulation of miR-200c significantly inhibited cell migration and invasion in the BC cell lines. The luciferase reporter assay showed that RECK was a direct target of miR-200c. The knockdown of RECK in the BC cell lines treated with anti-miR-200c elevated the previously attenuated cell migration and invasion.Conclusion: Our findings indicated that miR-200c functions as oncogenes in BC and may provide a novel therapeutic strategy for the treatment of BC. Keywords: miR-200c, bladder cancer, migration, invasion, RECK

  8. Prenatal Detection of Bladder Wall Involvement in Invasive Placentation with Sequential Two-dimensional and Adjunctive Three-dimensional Ultrasonography

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    Min-Min Chou

    2009-03-01

    Conclusion: 3D US may be a useful adjunctive tool in refining 2D ultrasonographic techniques to identify the extent and degree of placental invasion of the bladder. The advantages of 3D US are: (1 a multiplanar image display allows viewing of sections from sagittal, coronal and axial planes at the same time, thereby more accurately determining the location and extent of placental invasion; (2 the viewing planes of the spatial angioarchitecture network can be arbitrarily manipulated to better delineate the aberrant vessels protruding into the bladder; (3 3D reconstruction images can be clearly displayed by live 3D in a rotation mode for a better illustrative effect.

  9. Single-cell sequencing analysis characterizes common and cell-lineage-specific mutations in a muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Li, Yingrui; Xu, Xun; Song, Luting

    2012-01-01

    sequencing of 66 individual tumor cells from a muscle-invasive bladder transitional cell carcinoma (TCC). Analyses of the somatic mutant allele frequency spectrum and clonal structure revealed that the tumor cells were derived from a single ancestral cell, but that subsequent evolution occurred, leading...... to two distinct tumor cell subpopulations. By analyzing recurrently mutant genes in an additional cohort of 99 TCC tumors, we identified genes that might play roles in the maintenance of the ancestral clone and in the muscle-invasive capability of subclones of this bladder cancer, respectively...

  10. Malignant glandular lesions and glandular differentiation in invasive/noninvasive urothelial carcinoma of the urinary bladder.

    Science.gov (United States)

    Behzatoğlu, Kemal

    2011-12-01

    Although the lumen of the urinary bladder is covered with only urothelial epithelium, malign glandular lesions (eg, nonurachal adenocarcinoma) and benign lesions (eg, cystitis cystica and cystitis glandularis) can also rarely occur in this site due to its characteristic embryologic development. Glandular differentiation is uncommon in urothelial carcinomas and is even less common in noninvasive urothelial cancers. In addition, in situ urothelial carcinomas are more likely to progress in the presence of glandular differentiation toward high-grade urothelial carcinomas and/or aggressive urothelial carcinomas. Pure nonurachal adenocarcinomas and mixed carcinomas (urothelial carcinoma and adenocarcinoma) are very rare, and their pathogenesis is not clear. Most of the nonurachal adenocarcinomas are thought to arise on the grounds of cystitis glandularus with intestinal metaplasia. Here, I present 2 cases with noninvasive urothelial carcinoma with substantial glandular differentiation showing progression to signet ring cell carcinoma and invasive urothelial carcinoma, one case with mixed carcinoma (urothelial carcinoma and adenocarcinoma) and another case with pure adenocarcinoma developing from cystitis glandularis with intestinal metaplasia, and discuss malign glandular lesions in the bladder and invasive/noninvasive urothelial carcinomas with glandular differentiation.

  11. Combined modality program with possible organ preservation for invasive bladder carcinoma: Results of RTOG protocol 85-12

    Energy Technology Data Exchange (ETDEWEB)

    Tester, W.; Porter, A.; Asbell, S.; Coughlin, C.; Heaney, J.; Krall, J.; Martz, K.; Venner, P.; Hammond, E. (Radiation Therapy Oncology Group, Philadelphia, PA (United States))

    1993-04-02

    This Phase 2 study was designed to test the tolerance and effectiveness of concurrent cisplatin-radiotherapy in the treatment of invasive bladder cancer. Objectives were to determine toxicity, complete response rate, bladder preservation rate, and survival. Patients with invasive bladder cancer, clinical Stages T2--4, NO-2 or NX, MO were treated with pelvic radiotherapy 40 Gy in 4 weeks and cisplatin 100 mg/m[sup 2] on days 1 and 22. Complete responders were given an additional 24 Gy bladder boost plus a third dose of cisplatin; patients with residual tumor after 40 Gy were assigned radical cystectomy. The complete remission rate following cisplatin and 40 Gy for evaluable cases was 31/47 (66%). Acute toxicity was acceptable with only two patients not completing induction therapy. Patients with poorly differentiated tumors were more likely to achieve complete remission. Of fully evaluable patients, 28/42 (67%) achieved complete remission with induction therapy, 11 remain continuously in remission, and eight have relapsed with bladder as the only site of failure. Five of these eight cases relapsed with noninvasive tumor. Of the 14 patients who failed to achieve complete remission, only three remain disease-free. Median survival is not reached, with 17/42 (19/48) deaths reported. Actuarial survival is 64% at 3 years. This combined cisplatin-radiotherapy regime was moderately well-tolerated and associated with tumor clearance in 66% of patients treated. Isolated bladder recurrences with invasive carcinoma are infrequent. Better definition of pretreatment selection criteria is needed if combined modality treatment is to achieve disease control and organ preservation for patients with bladder cancer. 37 refs., 3 figs., 5 tabs.

  12. Can neutrophil to lymphocyte ratio predict lamina propria invasion in patients with non muscle invasive bladder cancer?

    Science.gov (United States)

    Cimen, Haci Ibrahim; Halis, Fikret; Saglam, Hasan Salih; Gokce, Ahmet

    2017-01-01

    ABSTRACT Objective Recent studies have demonstrated the role of systemic inflammation in the development and progression of cancer. In this study, we evaluated whether preoperatively measured neutrophil-to-lymphocyte ratio (NLR) can predict lamina propria invasion in patients with non-muscle-invasive bladder cancer (NMIBC). Material and Methods We reviewed the medical records of 304 consecutive and newly diagnosed patients with bladder cancer who had been treated with transurethral resection between January 2008 and June 2014. In total, 271 patients were included in the study and the patients were divided into two groups according to the pathological stage (Group 1: Ta, Group 2: T1). NLR was calculated by dividing the absolute neutrophil count (N) by the absolute lymphocyte count (L). Results In total, 271 patients (27 women and 244 men) were enrolled. Mean age was higher in Group 2 than in Group 1 (67.3±10.8 vs. 62.9±10.8, pblood cell (WBC) and N counts were statistically insignificant (7.63±1.87 vs. 7.69±1.93, p=0.780; 4.72±1.54 vs. 4.46±1.38, p=0.140; respectively), L was significantly lower and NLR was significantly higher in Group 2 than in Group 1 (2.07±0.75 vs. 2.4±0.87, p=0.001; 2.62±1.5 vs. 2.19±1.62, p=0.029; respectively). Conclusion Our data indicate that high NLR and low L are statistically associated with T1 stage, whereas low L are able to predict lamina propria invasion in patients with NMIBC. These findings suggest that pretreatment measurement of NLR may provide valuable information for the clinical management of patients with NMIBC. Prospective studies are now required to further validate the role of NLR as a risk factor in NMIBC. PMID:28124528

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

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    Ganglong Yang

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

  14. Utility of the novel bladder preservation therapy, BOAI-CDDP-radiation (OMC-regimen), for elderly patients with invasive bladder cancer.

    Science.gov (United States)

    Azuma, Haruhito; Inamoto, Teruo; Ibuki, Naokazu; Ubai, Takanobu; Kotake, Yatsugu; Takahara, Kiyoshi; Kiyama, Satoshi; Nomi, Hayahito; Uehara, Hiroshi; Komura, Kazumasa; Yamamoto, Kazuhiro; Narumi, Yoshihumi; Katsuoka, Yoji

    2011-01-01

    In this study, we investigated the novel bladder preservation therapy, the balloon-occluded arterial infusion (BOAI) of cisplatin/gemcitabine, concomitantly with hemodialysis, along with concurrent irradiation [the 'Osaka Medical College (OMC)-regimen'] in patients >70 years of age with muscle-invasive bladder cancer. Eighty-three such patients were assigned to receive either the OMC-regimen (n=56) or cystectomy (n=27). The OMC-regimen patients who failed to achieve complete response (CR) underwent cystectomy, or secondary BOAI with gemcitabine (1600 mg). The OMC-regimen, which delivers an extremely high concentration of anti-cancer agent to the tumor site without systemic adverse effects, yielded CR in >90% (39/43) of patients with locally invasive tumors [70% (39/56) of all patients including those with T4 and N+ disease]. None of the CR patients showed recurrence after a mean follow-up of 162 (range, 35-683) weeks, and 2 patients died of unrelated causes. The 5- and 12-year overall survival rates were 92.7 and 69.5% (vs. 59.6 and 20.9% for cystectomy; POMC-regimen group was significantly greater than that in the cystectomy group (median, 77; range, 70-98; vs. 74; 70-79; pOMC-regimen is a useful bladder preservation strategy for elderly patients with locally invasive bladder cancer, not only for those for whom cystectomy has been indicated, but also for patients whose condition is not amenable to curative treatment and for whom palliation would otherwise seem the only option.

  15. MicroRNA-3713 regulates bladder cell invasion via MMP9.

    Science.gov (United States)

    Wu, Wen-Bo; Wang, Wei; Du, Yi-Heng; Li, Hao; Xia, Shu-Jie; Liu, Hai-Tao

    2016-08-31

    Transitional cell carcinoma (TCC) is the most common type of bladder cancer but its carcinogenesis remains not completely elucidated. Dysregulation of microRNAs (miRNAs) is well known to be involved in the development of various cancers, including TCC, whereas a role of miR-3713 in the pathogenesis of TCC has not been appreciated. Here, we reported that significantly higher levels of matrix metallopeptidase 9 (MMP9), and significantly lower levels of miR-3713 were detected in TCC tissue, compared to the adjacent non-tumor tissue, and were inversely correlated. Moreover, the low miR-3713 levels in TCC specimens were associated with poor survival of the patients. In vitro, overexpression of miR-3713 significantly decreased cell invasion, and depletion of miR-3713 increased cell invasion in TCC cells. The effects of miR-3713 on TCC cell growth appeared to result from its modification of MMP9 levels, in which miR-3713 was found to bind to the 3'-UTR of MMP9 mRNA to inhibit its protein translation in TCC cells. This study highlights miR-3713 as a previously unrecognized factor that controls TCC invasiveness, which may be important for developing innovative therapeutic targets for TCC treatment.

  16. Bladder Contracture – A Rare and Serious Side Effect of Intravesical Bacillus Calmette-Guérin Therapy

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    Cindy Garcia

    2016-01-01

    Full Text Available Instillation of intravesical bacillus Calmette-Guérin (BCG is an effective treatment for non-muscle invasive bladder cancer (NMIBC. The high incidence of side effects may limit its tolerability in patients. Local side effects including cystitis and hematuria are common but generally self-limiting. Bladder contractures are a rare but serious consequence of BCG treatment. In this case, an 82 year-old male developed BCG reactivation and subsequent bladder contractures following transurethral resection of the prostate (TURP three years post-BCG. To our knowledge, this is the first reported case of BCG reactivation post-TURP leading to the rare but serious effect of bladder contractures.

  17. Age at diagnosis, obesity, smoking, and molecular subtypes in muscle-invasive bladder cancer.

    Science.gov (United States)

    Sun, Xuezheng; Hoadley, Katherine A; Kim, William Y; Furberg, Helena; Olshan, Andrew F; Troester, Melissa A

    2017-06-01

    Heterogeneity of muscle-invasive bladder cancer (MIBC) has been characterized using whole-genome mRNA expression data, showing distinct molecular and clinicopathological characteristics by subtypes. However, associations between risk factors and molecular subtypes have not been reported. Four previously published schemes were used to categorize molecular subtypes in 372 MIBC patients from the Cancer Genome Atlas (TCGA). Data on gene expression (RNA-seq), demographic, and clinicopathological characteristics were retrieved through TCGA data portal. Polytomous logistic regression was used to estimate the associations of subtypes by different schemes with age at diagnosis, obesity, and smoking. While some quantitative variation was evident, distinct molecular subtype schemes showed considerable consistency in the association with the risk factors. Generally, compared to patients with luminal-like tumors, patients with basal-like subtypes were more likely to be older (OR75 + yrs vs. obese (ORobese vs. normal range = 1.30-3.05), and to start smoking at early age (ORcancer risk factors are needed to further define etiologic heterogeneity for bladder cancer.

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

    Science.gov (United States)

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

    2015-01-01

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

  19. Inhibiting Invasion into Human Bladder Carcinoma 5637 Cells with Diallyl Trisulfide by Inhibiting Matrix Metalloproteinase Activities and Tightening Tight Junctions

    Directory of Open Access Journals (Sweden)

    Yung Hyun Choi

    2013-10-01

    Full Text Available Diallyl trisulfide (DATS, an organosulfur compound in garlic, possesses pronounced anti-cancer potential. However, the anti-invasive mechanism of this compound in human bladder carcinoma is not fully understood. In this study, we evaluated the anti-invasive effects of DATS on a human bladder carcinoma (5637 cell line and investigated the underlying mechanism. The results indicated that DATS suppressed migration and invasion of 5637 cells by reducing the activities and expression of matrix metalloproteinase (MMP-2 and MMP-9 at both the protein and mRNA levels. DATS treatment up-regulated expression of tissue inhibitor of metalloproteinase (TIMP-1 and TIMP-2 in 5637 cells. The inhibitory effects of DATS on invasiveness were associated with an increase in transepithelial electrical resistance and repression of the levels of claudin family members. Although further studies are needed, our data demonstrate that DATS exhibits anti-invasive effects in 5637 cells by down-regulating the activity of tight junctions and MMPs. DATS may have future utility in clinical applications for treating bladder cancer.

  20. Lymph node density in muscle-invasive transitional cell carcinoma of the urinary bladder; De novo versus progressive disease.

    Science.gov (United States)

    Elabbady, Ahmed; Hashad, Mohamed Mohieeldin; Kotb, Ahmed Fouad; Abdullah, Dina Mohamed; Beltagy, Ahmad

    2017-01-01

    The prognosis of bladder cancer patients with positive lymph node (LN) disease is affected by both the extent of lymphadenectomy and LN density retrieved during radical cystectomy. This study aimed at assessing the differences in LN metastasis between patients who presented primarily with muscle-invasive transitional cell carcinoma of the bladder "de novo disease" versus "progressive disease." The latter is defined as patients who progressed to muscle-invasive bladder cancer (MIBC) following prior conservative management of a non-muscle-invasive disease. Data were prospectively collected from consecutive 41 radical cystectomies that were divided into two groups: Group I included de novo MIBC cases and Group II included progressive MIBC cases. The median age was 60 years (44-75). Thirty-four patients exhibited de novo disease versus 7 patients who presented as progressive MIBC with a median duration of 9 months between the resection of the first non-invasive tumor and the diagnosis of progressive MIBC (range: 6-56 months). The median number of retrieved LNs in both groups was 15 LNs (range: 4-36). Ten patients (24.39%) had positive pathological LN disease; distributed as 9 patients in Group I and 1 patient in Group II. The median LN density of LN-positive patients was 15.73% (6.46 % in Group I, 28.57% in Group II). Five patients had LN density >20%. Although non-muscle-invasive urothelial bladder tumor may progress to muscle-invasive disease, it still carries less aggressive course than de novo MIBC based on differences in LN metastasis and density.

  1. Tuberculosis complications after BCG treatment for urinary bladder cancer.

    Science.gov (United States)

    Naudžiūnas, Albinas; Juškaitė, Rūta; Žiaugrytė, Indrė; Unikauskas, Alvydas; Varanauskienė, Eglė; Mašanauskienė, Edita

    2012-01-01

    Bacillus Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis that has been effectively used in the treatment of non-muscle invasive bladder carcinoma. The complications of this treatment are uncommon, and the causes of dissemination are still discussed. We report a case of disseminated tuberculosis in a 66-year-old smoking man without a history of pulmonary diseases, who underwent immunotherapy with BCG after the initial surgical treatment of bladder cancer. After the last BCG instillation, he developed a fever. The diagnosis of sepsis was not confirmed, and miliary pulmonary tuberculosis was suspected. The diagnosis was confirmed by clinical manifestation, computed tomography of the lungs, and histological examination.

  2. 同期经尿道电切治疗非肌层浸润膀胱癌合并前列腺增生20例%Simultaneous transurethral resection of normuscle invasive bladder tumor and benign prostatic hyperplasia in 20 cases

    Institute of Scientific and Technical Information of China (English)

    江敦勤; 黄玉良; 陆兆祥

    2012-01-01

    Objective To evaluate the effect of simultaneous transurethral resection of bladder tumor ( TURBT ) and benign prostatic hyperplasia ( TURP ) on nonmuscle invasive bladder cancer with benign prostatic hyperplasia( BPH ). Methods The clinical data of 20 patients with noninvasive bladder tumor combined with prostatic hyperplasia, who underwent simultaneous transurethral resection of bladder tumor and prostate were retrospectively analyzed. Results All 20 patients finished operation without transurethral resection syndromes. Urinate unobstructed after pull of the catheter for 5 ~ 7 days (I - PSS < 5 scores ). All patients were followed - up, and 3 cases( 15% ) of heter-otopic recurrence bladder cancer arose. The location of recurrence was not in the bladder neck, prostatic fossa or urethra. Conclusion Simultaneous transurethral resection of bladder tumors and prostate for the patients of noninvasive bladder tumor combined with prostatic hyperplasia is safe and effective,which does not increase the chance of cancer implantation in bladder neck, prostatic fossa or urethra.%目的 评估同期行经尿道膀胱肿瘤电切术(TURBt)和前列腺电切术(TURP)治疗非肌层浸润性膀胱癌合并前列腺增生患者的可行性.方法 对同期行经尿道膀胱肿瘤电切术及经尿道前列腺电切术的20例非肌层浸润膀胱癌合并前列腺增生患者的临床资料进行回顾性分析.结果 全部患者术中均未出现经尿道电切综合征.5~7 d后拔尿管均排尿通畅(I-PSS评分<5分).术后随访,3例出现膀胱癌异位复发,复发率15%,复发位置均未见于膀胱颈、前列腺及尿道.结论 同期行TURBt+TURP治疗非肌层浸润性膀胱癌合并前列腺增生安全可靠,不增加膀胱颈、前列腺窝和尿道的肿瘤种植性转移几率.

  3. Stromal proteome expression profile and muscle-invasive bladder cancer research

    Directory of Open Access Journals (Sweden)

    Niu Haitao

    2012-08-01

    Full Text Available Abstract Background To globally characterize the cancer stroma expression profile of muscle-invasive transitional cell carcinoma and to discuss the cancer biology as well as biomarker discovery from stroma. Laser capture micro dissection was used to harvest purified muscle-invasive bladder cancer stromal cells and normal urothelial stromal cells from 4 paired samples. Two-dimensional liquid chromatography tandem mass spectrometry was used to identify the proteome expression profile. The differential proteins were further analyzed using bioinformatics tools and compared with the published literature. Results We identified 868/872 commonly expressed proteins and 978 differential proteins from 4 paired cancer and normal stromal samples using laser capture micro dissection coupled with two-dimensional liquid chromatography tandem mass spectrometry. 487/491 proteins uniquely expressed in cancer/normal stroma. Differential proteins were compared with the entire list of the international protein index (IPI, and there were 42/42 gene ontology (GO terms exhibited as enriched and 8/5 exhibited as depleted in cellular Component, respectively. Significantly altered pathways between cancer/normal stroma mainly include metabolic pathways, ribosome, focal adhesion, etc. Finally, descriptive statistics show that the stromal proteins with extremes of PI and MW have the same probability to be a biomarker. Conclusions Based on our results, stromal cells are essential component of the cancer, biomarker discovery and network based multi target therapy should consider neoplastic cells itself and corresponding stroma as whole one.

  4. The role of adjuvant chemotherapy following cystectomy for invasive bladder cancer: a prospective comparative trial.

    Science.gov (United States)

    Skinner, D G; Daniels, J R; Russell, C A; Lieskovsky, G; Boyd, S D; Nichols, P; Kern, W; Sakamoto, J; Krailo, M; Groshen, S

    1991-03-01

    We assigned 91 patients with deeply invasive, pathological stage P3, P4 or N+ and Mo transitional cell carcinoma of the bladder (with or without squamous or glandular differentiation) to adjuvant chemotherapy or to observation after radical cystectomy and pelvic lymph node dissection. For most patients chemotherapy was planned as 4 courses at 28-day intervals of 100 mg./M.2 cisplatin, 60 mg./M.2 doxorubicin and 600 mg./M.2 cyclophosphamide. A significant delay was shown in the time to progression (p = 0.0010) with 70% of the patients assigned to chemotherapy free of disease at 3 years compared to 46% in the observation group. Median survival time for patients in the chemotherapy group was 4.3 years compared to 2.4 years in the observation group (p = 0.0062). In addition to treatment groups, important prognostic factors included age, gender and lymph node status. The number of involved lymph nodes was the single most important variable. We recommend adjuvant chemotherapy for patients with invasive transitional cell carcinoma after definitive surgical resection.

  5. MicroRNA-186 regulates the invasion and metastasis of bladder cancer via vascular endothelial growth factor C.

    Science.gov (United States)

    He, Xuefeng; Ping, Jigen; Wen, Duangai

    2017-10-01

    The present study aimed to investigate the expression of microRNA (miRNA or miR)-186 in tumor tissue, blood and urine from patients with bladder cancer. The mechanism by which miR-186 regulates the invasion and metastasis of bladder cancer was also assessed. A total of 76 patients who underwent surgical resection of bladder cancer tissues between August 2012 and January 2016 were included in the present study. Blood and urine samples were also collected from the 76 patients and another 66 healthy subjects. Expression of vascular endothelial growth factor C (VEGF-C) mRNA and miR-186 was measured using reverse transcription-quantitative polymerase chain reaction. Western blot analysis was performed to assess VEGF-C protein expression in tumor tissues. The content of VEGF-C protein in blood and urine samples was measured using an enzyme-linked immunosorbent assay. To identify the direct interaction between miR-186 and VEGF-C mRNA, a dual luciferase reporter assay was performed. The present findings demonstrated that VEGF-C mRNA expression in tumor tissues, blood and urine of bladder cancer patients was upregulated. VEGF-C protein expression in bladder cancer tissues was also enhanced. VEGF-C protein content in blood and urine from bladder cancer patients was elevated, consistent with the results for VEGF-C mRNA. Expression of miR-186 was reduced in tumor tissues, blood and urine. Dual luciferase reporter assay demonstrated that miR-186 regulated the expression of VEGF-C by binding with its 3'-untranslated region. Therefore, the results of the present study indicate that the expression of VEGF-C mRNA and protein is upregulated in tumor tissues, blood and urine from patients with bladder cancer, while that of miR-186 is downregulated in these samples. miR-186 potentially regulates the invasion and metastasis of bladder cancer via VEGF-C, and may become a gene marker for bladder cancer in the future.

  6. [EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update].

    Science.gov (United States)

    Babjuk, M; Oosterlinck, W; Sylvester, R; Kaasinen, E; Böhle, A; Palou-Redorta, J; Rouprêt, M

    2012-01-01

    To present the 2011 European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC). Literature published between 2004 and 2010 on the diagnosis and treatment of NMIBC was systematically reviewed. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned. Tumours staged as Ta, T1, or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection (TUR) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TUR is essential for the patient's prognosis. Where the initial resection is incomplete or where a high-grade or T1 tumour is detected, a second TUR should be performed within 2-6 wk. In papillary tumours, the risks of both recurrence and progression may be estimated for individual patients using the scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups (separately for recurrence and progression) is pivotal to recommending adjuvant treatment. For patients with a low risk of tumour recurrence and progression, one immediate instillation of chemotherapy is recommended. Patients with an intermediate or high risk of recurrence and an intermediate risk of progression should receive one immediate instillation of chemotherapy followed by a minimum of 1 yr of bacillus Calmette-Guérin (BCG) intravesical immunotherapy or further instillations of chemotherapy. Papillary tumours with a high risk of progression and CIS should receive intravesical BCG for 1 yr. Cystectomy may be offered to the highest risk patients, and it is at least recommended in BCG failure patients. These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice. Copyright © 2011 AEU. Published by Elsevier España. All rights reserved.

  7. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update.

    Science.gov (United States)

    Babjuk, Marko; Oosterlinck, Willem; Sylvester, Richard; Kaasinen, Eero; Böhle, Andreas; Palou-Redorta, Juan; Rouprêt, Morgan

    2011-06-01

    To present the 2011 European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC). Literature published between 2004 and 2010 on the diagnosis and treatment of NMIBC was systematically reviewed. Previous guidelines were updated, and the level of evidence (LE) and grade of recommendation (GR) were assigned. Tumours staged as Ta, T1, or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection (TUR) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TUR is essential for the patient's prognosis. Where the initial resection is incomplete or where a high-grade or T1 tumour is detected, a second TUR should be performed within 2-6 wk. In papillary tumours, the risks of both recurrence and progression may be estimated for individual patients using the scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups-separately for recurrence and progression-is pivotal to recommending adjuvant treatment. For patients with a low risk of tumour recurrence and progression, one immediate instillation of chemotherapy is recommended. Patients with an intermediate or high risk of recurrence and an intermediate risk of progression should receive one immediate instillation of chemotherapy followed by a minimum of 1 yr of bacillus Calmette-Guérin (BCG) intravesical immunotherapy or further instillations of chemotherapy. Papillary tumours with a high risk of progression and CIS should receive intravesical BCG for 1 yr. Cystectomy may be offered to the highest risk patients, and it is at least recommended in BCG failure patients. The long version of the guidelines is available from the EAU Web site (www.uroweb.org). These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice. Copyright © 2011

  8. Muscle-invasive bladder cancer in a young adult: a case report and a review of the literature.

    Science.gov (United States)

    Nabbout, Philippe; Eldefrawy, Ahmed; Engles, C Dirk; Culkin, Daniel J; Slobodov, Gennady

    2013-01-01

    The peak incidence of bladder cancer (BC) is in the sixth decade of life. Muscle-invasive bladder cancer (MIBC) in young adults is extremely rare. We report a case of MIBC in a 28-year-old smoking male patient. The patient presented with hematuria and flank pain for which he underwent a computerized tomography (CT) scan of the abdomen and pelvis with and without contrast. The CT scan showed a 6 cm mass on the left side of the trigone extending to the left urteric orifice and left hydronephrosis, but no lymphadenopathy was noted. The patient then underwent a left nephrostomy tube placement followed by trans-urethral resection of bladder tumor (TURBT). The tumor involved both ureteric orifices and extended to the prostatic urethra. Complete resection was not feasible. Pathology showed high-grade T1 urothelial carcinoma. CT scan of the chest showed no distant lung metastasis. The patient then elected to undergo radical cystectomy with ileal conduit urinary diversion. Final pathology revealed T2a N0 urothelial carcinoma of the bladder. Our aim is to present our experience and review the literature for the natural history and oncological and quality of life outcomes of urothelial carcinoma of the bladder in young patients.

  9. Novel somatic mutations identified by whole-exome sequencing in muscle-invasive transitional cell carcinoma of the bladder

    OpenAIRE

    PAN, HUIXING; Xu, Xiaojian; WU, DEYAO; QIU, QIAOCHENG; Zhou, Shoujun; He, Xuefeng; Zhou, Yunfeng; Qu, Ping; Hou, Jianquan; He, Jun; Zhou, Jian

    2016-01-01

    Transitional cell carcinoma (TCC) is the one of the most commonly observed types of cancer globally. The identification of novel disease-associated genes in TCC has had a significant effect on the diagnosis and treatment of bladder cancer; however, there may be a large number of novel genes that have not been identified. In the present study, the exomes of two individuals who were diagnosed with muscle-invasive TCC (MI-TCC) were sequenced to investigate potential variants. Subsequently, follo...

  10. Apigenin promotes apoptosis, inhibits invasion and induces cell cycle arrest of T24 human bladder cancer cells.

    Science.gov (United States)

    Zhu, Yi; Mao, Yeqing; Chen, Hong; Lin, Yiwei; Hu, Zhenghui; Wu, Jian; Xu, Xin; Xu, Xianglai; Qin, Jie; Xie, Liping

    2013-06-01

    Apigenin (4',5,7-trihydroxyflavone) was recently shown effective in inhibiting several cancers. The aim of this study was to investigate the effect and mechanism of apigenin in the human bladder cancer cell line T24 for the first time. T24 cells were treated with varying concentrations and time of apigenin. Cell viability was evaluated by MTT assay. Cell motility and invasiveness were assayed by Matrigel migration and invasion assay. Flow cytometry and western blot analysis were used to detect cell apoptosis, cell cycle and signaling pathway. The results demonstrated that apigenin suppressed proliferation and inhibited the migration and invasion potential of T24 bladder cancer cells in a dose- and time-dependent manner, which was associated with induced G2/M Phase cell cycle arrest and apoptosis. The mechanism of action is like to involve PI3K/Akt pathway and Bcl-2 family proteins. Apigenin increased caspase-3 activity and PARP cleavage, indicating that apigenin induced apoptosis in a caspase-dependent way. These findings suggest that apigenin may be an effective way for treating human bladder cancer.

  11. Evaluation of acridine orange fluorescence in exfoliative urinary cytology for diagnosing bladder carcinoma.

    Science.gov (United States)

    Liu, Ranlu; Tian, Zhentao; Wang, Jin; Zhang, Zhihong; Xu, Yong

    2012-10-01

    This study reviewed acridine orange fluorescence (AO-F) in exfoliative urinary cytology results of 1,016 inpatients with urothelial cell carcinoma of the bladder and 804 outpatients to investigate the value of AO-F in the diagnosis of bladder cancer. A total of 1,016 bladder cancer inpatients from October 1995 to October 2005 and 804 outpatients from January 2004 to January 2006 were enrolled in this study. Each patient provided the morning urine specimen of 30-50 ml in a sterile container. Urine sediments were stained by acridine orange and observed with a fluorescence microscope; 60 bladder cancer inpatients from January 2006 to July 2007 were also chosen for the control study of three different detection methods, including AO-F, hematoxylin and eosin and Feulgen staining. Of the 1,016 bladder carcinoma samples analyzed, 793 were AO-F positive. Total positive rate of AO-F was 78.05 %. The positive rate was 74.69 % (611/818) for non-muscle invasive bladder carcinoma and 91.91 % (182/198) for muscle invasive bladder carcinoma. A significant correlation of AO-F positivity with clinical stage was observed (P < 0.01). The positive rates among various pathological grades were 66.7 % (32/48) for G1, 67.5 % (319/474) for G2 and 90.4 % (413/457) for G3 with significant differences (P < 0.01). For the 804 outpatients, the sensitivity and specificity of bladder carcinoma were 77.11 and 85.29 %, respectively. With its high sensitivity and specificity, AO-F is superior to other detection methods for bladder carcinoma detection. In addition, it is familiar, non-invasive, quick, cheap and easily repeatable.

  12. Sperm associated antigen 9 plays an important role in bladder transitional cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Deepika Kanojia

    Full Text Available BACKGROUND: Majority of bladder cancer deaths are caused due to transitional cell carcinoma (TCC which is the most prevalent and chemoresistant malignancy of urinary bladder. Therefore, we analyzed the role of Sperm associated antigen 9 (SPAG9 in bladder TCC. METHODOLOGY AND FINDINGS: We examined SPAG9 expression and humoral response in 125 bladder TCC patients. Four bladder cancer cell lines were assessed for SPAG9 expression. In addition, we investigated the effect of SPAG9 ablation on cellular proliferation, cell cycle, migration and invasion in UM-UC-3 bladder cancer cells by employing gene silencing approach. Our SPAG9 gene and protein expression analysis revealed SPAG9 expression in 81% of bladder TCC tissue specimens. High SPAG9 expression (>60% SPAG9 positive cells was found to be significantly associated with superficial non-muscle invasive stage (P = 0.042 and low grade tumors (P = 0.002 suggesting SPAG9 putative role in early spread and tumorigenesis. Humoral response against SPAG9 was observed in 95% of patients found positive for SPAG9 expression. All four bladder cancer cell lines revealed SPAG9 expression. In addition, SPAG9 gene silencing in UM-UC-3 cells resulted in induction of G0-G1 arrest characterized by up-regulation of p16 and p21 and consequent down-regulation of cyclin E, cyclin D and cyclin B, CDK4 and CDK1. Further, SPAG9 gene silencing also resulted in reduction in cellular growth, and migration and invasion ability of cancer cells in vitro. CONCLUSIONS: Collectively, our data in clinical specimens indicated that SPAG9 is potential biomarker and therapeutic target for bladder TCC.

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

    Directory of Open Access Journals (Sweden)

    Steve Goodison

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

  14. Intra-arterial cisplatin and concurrent radiation for invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Miyanaga, Naoto; Ohtani, Mikinobu; Noguchi, Ryosuke (Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine) (and others)

    1991-10-01

    Fifteen patients with invasive bladder cancer were treated with selective intra-arterial cisplatin and external beam radiotherapy (30.6 Gy over 3 weeks) prior to a planned cystectomy. Cisplatin, in total 200 mg, was administered via bilateral internal iliac artery infusion during the course of radiotherapy. Seven patients were evaluated for local response. Partial response (PR) was revealed in 4, and minor response (MR) in 3. Ten patients received total cystectomy, and pathological effects by the criteria adipted by Japanese Urological Association and The Japanese Society of Pathology, were as follows: Ef.3 in 1 case, Ef.2 in 6. Ef.1b in 1 and Ef.1a in 2. Down staging was observed in 8 patients from the clinical to the pathological stage. Thirteen patients are alive for 21 months. Two patients have died (1 lung infarction, 1 pancreatic cancer). Though nausea and sciatica-like pain were observed in some cases, there were no severe systemic side effects such as bone marrow suppression and renal toxicity. From these results it is concluded that this therapeutic modality could be effective in the preoperative work-up of candidates for total cystectomy, and also that it could be useful in the treatment of patients in whom total cystectomy is contraindicated. (author).

  15. A Real-Time Non-invasive Auto-bioluminescent Urinary Bladder Cancer Xenograft Model.

    Science.gov (United States)

    John, Bincy Anu; Xu, Tingting; Ripp, Steven; Wang, Hwa-Chain Robert

    2017-02-01

    The study was to develop an auto-bioluminescent urinary bladder cancer (UBC) xenograft animal model for pre-clinical research. The study used a humanized, bacteria-originated lux reporter system consisting of six (luxCDABEfrp) genes to express components required for producing bioluminescent signals in human UBC J82, J82-Ras, and SW780 cells without exogenous substrates. Immune-deficient nude mice were inoculated with Lux-expressing UBC cells to develop auto-bioluminescent xenograft tumors that were monitored by imaging and physical examination. Lux-expressing auto-bioluminescent J82-Lux, J82-Ras-Lux, and SW780-Lux cell lines were established. Xenograft tumors derived from tumorigenic Lux-expressing auto-bioluminescent J82-Ras-Lux cells allowed a serial, non-invasive, real-time monitoring by imaging of tumor development prior to the presence of palpable tumors in animals. Using Lux-expressing auto-bioluminescent tumorigenic cells enabled us to monitor the entire course of xenograft tumor development through tumor cell implantation, adaptation, and growth to visible/palpable tumors in animals.

  16. Orthotopic urinary diversion after radical cystectomy in treatment of muscle invasive bladder cancer.

    Science.gov (United States)

    Jovan, Hadži-Djokić; Vladan, Andrejević; Tomislav, Pejčić; Miodrag, Aćimović; Uroš, Babić; Miodrag, Stanić; Zoran, Džamić

    2014-01-01

    Surgical treatment of invasive carcinoma of the bladder in males includes total cystectomy removal of the prostate, seminal vesicles, and the distal parts of the urethers and the pelvic lymph node dissection as well. At this moment it is not possible to recommend a particular type of urinary diversion, but today in clinical practice commonly used derivative are ileal orthotopic neobladder as the continent one and ileal conduit as non-continent urinary diversion. Continent urinary diversion after radical cystectomy are the result of the application of technological innovation in surgery, but also knowledge, imagination and skill of well trained urologist. This type of operation significantly improves the quality of life in patients who underwent radical cystectomy, and the proposal is to operate whenever there is a possibility for this type of procedure. Also it is very important, during surgery to respect oncological principles, of complete removal of tumorous tissue and that the functional principle of ensur- ing that the patients have daytime and also nighttime continence later on after the surgery.

  17. p53-stabilizing agent CP-31398 prevents growth and invasion of urothelial cancer of the bladder in transgenic UPII-SV40T mice.

    Science.gov (United States)

    Madka, Venkateshwar; Zhang, Yuting; Li, Qian; Mohammed, Altaf; Sindhwani, Puneet; Lightfoot, Stan; Wu, Xue-Re; Kopelovich, Levy; Rao, Chinthalapally V

    2013-08-01

    The high prevalence of bladder cancer and its recurrence make it an important target for chemoprevention. About half of invasive urothelial tumors have mutations in p53. We determined the chemopreventive efficacy of a p53-stabilizing agent, CP-31398, in a transgenic UPII-SV40T mouse model of bladder transitional cell carcinoma (TCC) that strongly resembles human TCC. After genotyping, six-week-old UPII-SV40T mice (n = 30/group) were fed control (AIN-76A) or experimental diets containing 150 or 300 ppm of CP-31398 for 34 weeks. Progression of bladder cancer growth was monitored by magnetic resonance imaging. At 40 weeks of age, all mice were killed; urinary bladders were collected to determine weights, tumor incidence, and histopathology. There was a significant increase in bladder weights of transgenic versus wild-type mice (male: 140.2 mg vs 27.3 mg, P CP-31398-treated mice. Invasive papillary TCC incidence was 100% in transgenic mice fed control diet. Both male and female mice exposed to CP-31398 showed inhibition of invasive TCC. CP-31398 (300 ppm) completely blocked invasion in female mice. Molecular analysis of the bladder tumors showed an increase in apoptosis markers (p53, p21, Bax, and Annexin V) with a decrease in vascular endothelial growth factor in transgenic mice fed CP-31398. These results suggest that p53-modulating agents can serve as potential chemopreventive agents for bladder TCC.

  18. Re: Sequential Combination of Mitomycin C Plus Bacillus Calmette-Guerin (BCG Is More Effective but More Toxic Than BCG Alone in Patients with Non–Muscle-Invasive Bladder Cancer in Intermediate-and High-Risk Patients: Final Outcome of CUETO 93009, A Randomized Prospective Trial

    Directory of Open Access Journals (Sweden)

    Eduardo Solsona

    2015-03-01

    Full Text Available EAU Guideline recommendation in non-muscle invasive bladder cancer (NMIBC is that patients who have intermediate or high risk for recurrence and intermediate risk for progression should receive early single dose intravesical chemotherapy followed by maintenance or a minimum of 1 year of BCG. Intravesical Mitomycin C (MMC plus Bacillus Calmette-Guerin (BCG treatment schemes were studied. However, MMC+BCG were not found to be superior to BCG alone (1,2. In the present study, authors conducted a randomized prospective trial on combination of MMC+BCG (n=192 or BCG alone (n=190. EORTC definition of NMIBC intermediate and high-risk patientswere included in the study. Unlike previous reported studies, disease-free interval at 5 years for MMC+BCG was found to be significantly better (HR: 0.57; 95% CI, 0.39 -0,83; p=0.003 than BCG alone. In an interim analysis, excessive toxicity was observed in MMC+BCG than BCG alone group. Consequently MMC dose was reduced from 30 mg to 10 mg. However, toxicity remained higher in the MMC+BCG group. Especially in EORTC highrisk NMIBCs, MMC+BCG is better than BCG alone, but with worse toxicity. In conclusion, despite some limitations, the results of Solsona et al. provided a new potential bladder-sparing management alternative, but it has higher toxicity. Additional studies are required to confirm these findings and availability of a less toxic intravesical chemotherapeutic agent.

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Inhibition of nitric oxide is a good therapeutic target for bladder tumors that express iNOS.

    Science.gov (United States)

    Belgorosky, Denise; Langle, Yanina; Prack Mc Cormick, Bárbara; Colombo, Lucas; Sandes, Eduardo; Eiján, Ana María

    2014-01-30

    Bladder cancer is the second cause of death for urological tumors in man. When the tumor is nonmuscle invasive, transurethral resection is curative. On the other hand, radical cystectomy is the treatment chosen for patients with invasive tumors, but still under treatment, these patients have high risk of dying, by the development of metastatic disease within 5 years. It is therefore important to identify a new therapeutic target to avoid tumor recurrences and tumor progression. Nitric oxide (NO) is an important biological messenger known to influence several types of cancers. In bladder cancer, production of NO and expression and activity of inducible NO synthase was associated to recurrence and progression. The objective of this work was to analyze if inhibition of nitric oxide production could be considered a therapeutic target for bladder tumors expressing iNOS. Using a bladder cancer murine model with different invasiveness grade we have demonstrated that NO inhibition was able to inhibit growth of bladder tumors expressing iNOS. Furthermore, invasive properties of MB49-I orthotopic growth was inhibited using NO inhibitors. This paper also shows that levels of NO in urine can be correlated with tumor size. In conclusion, inhibition of NO could be considered as a therapeutic target that prevents tumor growth and progression. Also, urine NO levels may be useful for measuring tumor growth.

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

    Science.gov (United States)

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

    2017-09-27

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

  2. 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.

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

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

    2015-12-15

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

  4. Comparison of the efficacy and feasibility of laser enucleation of bladder tumor versus transurethral resection of bladder tumor: a meta-analysis.

    Science.gov (United States)

    Yang, Huan; Wang, Ning; Han, Shanfu; Male, Musa; Zhao, Chenming; Yao, Daqiang; Chen, Zhiqiang

    2017-08-23

    The transurethral resection of bladder tumor (TURBT) remains the most widely used method in the surgical treatment of the non-muscle invasive bladder tumor (NMIBT). Despite its popularity, the laser technique has been widely used in urology as an alternative, via the application of transurethral laser enucleation of bladder tumor. The aim of the present study was to compare the efficacy and feasibility between transurethral laser enucleation and transurethral resection of bladder tumor. A systematic search of the following databases was conducted: PubMed, Wed of Science, Cochrane Library, EMBASE, Google scholar, and Medline. The search included studies up to the 1st of January 2017. The outcomes of interest that were used in order to assess the two techniques included operation time, catheterization time, hospitalization time, obturator nerve reflex, bladder perforation, bladder irritation, 24-month-recurrence rate, and the postoperative adjuvant intravesical chemotherapy. A total of 13 trials with 2012 participants were included, of which 975 and 1037 underwent transurethral laser enucleation and transurethral resection of bladder tumor, respectively. No significant difference was noted in the operation time between the two groups, although significant differences were reported for the variables catheterization time, hospitalization time, obturator nerve reflex, bladder perforation, bladder irritation, and 24-month-recurrence rate. In the mitomycin and epirubicin subgroups, no significant differences were observed in the laser enucleation and TURBT methods with regard to the 24-month-recurrence rate. The laser enucleation was superior to TURBT with regard to the parameters obturator nerve reflex, bladder perforation, catheterization time, hospitalization time, and 24-month-recurrence rate. Moreover, laser enucleation can offer a more accurate result of the tumor's pathological stage and grade.

  5. Combined immunochemotherapy (CEP, M-VEP + BCG) in the treatment of invasive bladder tumors.

    Science.gov (United States)

    Damianov, C; Terziev, T; Koleva, P; Chuchkova, M

    1994-06-01

    Forty patients with invasive bladder tumors were consecutively treated and followed between June 1986 and February 1993. The treatment included systemic chemotherapy combining cyclophosphamide, epirubicin and cisplatin (CEP) or methotrexate, vinblastine, epirubicin and cisplatin (M-VEP) along with intravesically applied BCG vaccine. The treatment was well tolerated by the patients. No relevant toxic effects requiring hospitalization or fatalities due to the treatment were observed. Toxic manifestations of a hematologic nature were considerably less frequent than usual, nausea and vomiting being among the most frequently observed toxic signs on the second day of application of cisplatin. The side effects resulting from intravesically applied BCG vaccine showed no significant difference in terms of severity and variety from those due to its application in superficial tumors. A median follow-up of 50.3 months (range 6-80 months) showed an objective response to the treatment as follows: complete and partial response in 27 out of 40 (67.5%) and a complete clinical response in eight out of 40 (20%). Ten patients with partial response and stabilization had complete surgical response after operative treatment. The recurrence rate in patients with a complete response and a complete surgical response was 33% (six out of 18). The survival rate was 78% at 1 year, 70% at 2 years and 68% at 4 years. A complete response to the treatment of concomitant carcinoma in situ was observed in three patients. The lack of comparative and randomized studies and insufficient clinical experience did not allow an overall assessment of the therapeutic opportunities that our combined immunochemotherapy offers.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. ARID1A immunohistochemistry improves outcome prediction in invasive urothelial carcinoma of urinary bladder.

    Science.gov (United States)

    Faraj, Sheila F; Chaux, Alcides; Gonzalez-Roibon, Nilda; Munari, Enrico; Ellis, Carla; Driscoll, Tina; Schoenberg, Mark P; Bivalacqua, Trinity J; Shih, Ie-Ming; Netto, George J

    2014-11-01

    AT-rich interactive domain 1A (ARID1A) is tumor suppressor gene that interacts with BRG1 adenosine triphosphatase to form a SWI/SNF chromatin remodeling protein complex. Inactivation of ARID1A has been described in several neoplasms, including epithelial ovarian and endometrial carcinomas, and has been correlated with prognosis. In the current study, ARID1A expression in urothelial carcinoma (UC) of the bladder and its association with clinicopathological parameters and outcome are addressed. Five tissue microarrays were constructed from 136 cystectomy specimens performed for UC at our institution. Nuclear ARID1A staining was evaluated using immunohistochemistry. An H-score was calculated as the sum of the products of intensity (0-3) multiplied by extent of expression (0%-100%). Average H-score per case was used for statistical analysis. ARID1A expression was categorized in low and high using Youden index to define the cut point. ARID1A expression significantly increased from normal to noninvasive UC to invasive UC. For both tumor progression and cancer death, Youden index yielded an H-score of 288 as the optimal cut point for ARID1A expression. Low ARID1A expression showed a tendency for lower risk of tumor progression and cancer mortality. Adding ARID1A expression to pathologic features offers a better model for predicting outcome than pathologic features alone. Low ARID1A expression was more frequently seen in earlier stage disease. There was a tendency for low ARID1A expression to predict better outcome. More importantly, the findings indicate that adding ARID1A expression to pathologic features increases the goodness of fit of the predictive model.

  7. Outcomes of BCG Induction in High-Risk Non-Muscle-Invasive Bladder Cancer Patients (NMIBC): A Retrospective Cohort Study

    Science.gov (United States)

    Ghauri, Rashid; Ahmed, Monis J; Shah, Muhammad F; Nasir, Irfan ul Islam; Siddiqui, Jasim; Ahmed, Irfan; Mir, Khurram

    2017-01-01

    Non-muscle-invasive bladder cancer (NMIBC) is categorized into high-risk and low-risk groups. Although, bacillus Calmette-Guerin (BCG) is the recommended adjuvant therapy of high-risk bladder tumor, optimal schedule (induction versus maintenance) of this therapy is a subject of debate. The objective was to evaluate outcomes of induction BCG in high-risk NMIBC patients at Shaukat Khanum Memorial Cancer Hospital & Research Centre, Pakistan and retrospective cohort study conducted in the department of urology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Pakistan. Three-year disease-free survival and progression-free survival was the main outcome measure. Data of 68 high-risk (Ta and T1 with G3 or high-grade subtype) bladder cancer patients who underwent transurethral resection followed by six-weekly intravesical BCG instillation was included in the study. Recurrence was described as biopsy-proven bladder cancer; whereas the presence of muscle invasion was considered as progression. Disease-free survival and progression-free survival were defined as time intervals elapsed between the starting date of BCG instillation and recurrence or progression, respectively. Kaplan-Meier curve was employed to estimate the three-year study end-points. Disease-free survival at three years was observed to be 66.2% and progression-free survival at 86.8%. The use of induction BCG alone for high-risk patients of NMIBC is a viable option both in terms of effective disease-free and progression-free survival rates. PMID:28168135

  8. A great option for elderly patients with locally invasive bladder cancer, BOAI-CDDP-radiation (OMC regimen).

    Science.gov (United States)

    Azuma, Haruhito; Inamoto, Teruo; Takahara, Kiyoshi; Nomi, Hayahito; Hirano, Hajime; Uehara, Hiroshi; Komura, Kazumasa; Minami, Koichiro; Kouno, Junko; Kotake, Yatsugu; Abe, Hirokazu; Takagi, Shizuko; Ibuki, Naokazu; Yamamoto, Kazuhiro; Narumi, Yoshihumi; Kiyama, Satoshi

    2013-10-01

    We have developed a novel bladder preservation therapy, balloon-occluded arterial infusion (BOAI) of cisplatin/gemcitabine, concomitantly with hemodialysis, along with concurrent irradiation [the so-called 'OMC (Osaka Medical College) regimen']. The OMC regimen delivers an extremely high concentration of anticancer agent to the site of a tumor without systemic adverse effects, since more than 95% of free Pt was efficiently eliminated by hemodialysis, which enables short hospital stay. In this study, we investigated the efficiency of OMC regimen in patients aged over 70 years with muscle-invasive bladder cancer without metastasis. A total of 134 such patients were assigned to receive either the OMC regimen (n=89) or cystectomy (n=45). OMC regimen patients who failed to achieve CR underwent cystectomy, or secondary BOAI with gemcitabine (1,600 mg). The OMC regimen, which delivers an extremely high concentration of anticancer agent to the tumor site without systemic adverse effects, yielded CR in >91% (81/89) of patients. More than 96% (78/81) of the CR patients survived without recurrence with intact bladder after a mean follow-up of 164 (range 16-818) weeks. The 5- and 10-year bladder intact survival rates were 87.2 and 69.8%, and overall survival rates were 88.4 and 70.7% (vs. 59.9 and 33.3% for cystectomy, p=0.0002), respectively, although the median age in the OMC regimen group was significantly greater than in the cystectomy group (median, range = 77, 70-98 vs. 74, 70-89; p=0.0003). No patients suffered grade II or more severe toxicities; the oldest patient, aged 91 years, successfully completed this therapy. In conclusion, the OMC regimen is a useful bladder preservation strategy for elderly patients with locally invasive bladder cancer, not only in those for whom cystectomy is indicated, but also in patients whose condition is not amenable to curative treatment and for whom palliation would otherwise seem the only option.

  9. The novel bladder preservation therapy BOAI-CDDP-radiation (OMC-regimen): a new treatment option for invasive bladder cancer patients with lymph node metastasis.

    Science.gov (United States)

    Azuma, Haruhito; Inamoto, Teruo; Takahara, Kiyoshi; Nomi, Hayahito; Hirano, Hajime; Ibuki, Naokazu; Uehara, Hiroshi; Komura, Kazumasa; Minami, Koichiro; Uchimoto, Taizo; Saito, Kenkichi; Takai, Tomoaki; Tanda, Naoki; Yamamoto, Kazuhiro; Narumi, Yoshihumi; Kiyama, Satoshi

    2014-06-01

    We have developed a novel bladder preservation therapy for patients with muscle-invasive bladder cancer and lymph node metastasis: balloon-occluded arterial infusion (BOAI) of cisplatin/gemcitabine, with concomitant hemodialysis and irradiation [the so-called 'OMC (Osaka Medical College) regimen']. The OMC regimen delivers an extremely high concentration of anticancer agent to the site of the tumor, as well as the pelvic area, without causing any adverse systemic effects. In this study, we investigated the efficiency of the OMC regimen in 34 patients who underwent BOAI with cisplatin (100, 200 or 300 mg) along with 60 Gy of irradiation; patients who failed to achieve CR underwent secondary BOAI with gemcitabine (1,600 mg). The overall clinical response was 73.5% (CR: 35.3%; PR: 17.6%; SD: 20.6%). The 5-year overall and progression-free survival rates were 54.4% and 52.5%, respectively. For treatment failure, N2 stage was selected as a significant risk factor by simple and multiple logistic regression analyses. Cox proportional hazards analyses showed that N2 stage, T4 stage and the presence of hydronephrosis were significant risk factors for overall survival. Indeed, 55.6% of patients with N1 stage achieved a complete response (CR) (vs. 12.5% for N2 patients, p=0.0151), and 90% (9/10) of the CR patients survived without recurrence with an intact bladder after a mean follow-up of 85 (range 7-193) weeks. The 3-year progrssion-free survival rate with an intact bladder was 65.8% (vs. 37.5% for N2, p=0.034), and the 5-year overall survival rate was 71.8% (vs. 30.6% for N2, p=0.004). No patients suffered severe toxicities of Grade II or more; the oldest patient, aged 85 years, successfully completed this therapy. In conclusion, the OMC regimen can be regarded as a new option for patients with macroscopic lymph node involvement, especially those at stage N1. Therapy will improve the feasibility of radical cure even without the need for cystectomy in patients for whom

  10. TLR4- and TLR9-dependent effects on cytokines, cell viability, and invasion in human bladder cancer cells.

    Science.gov (United States)

    Olbert, Peter J; Kesch, Claudia; Henrici, Marcus; Subtil, Florentine S; Honacker, Astrid; Hegele, Axel; Hofmann, Rainer; Hänze, Jörg

    2015-03-01

    Adjuvant immunotherapy of bladder cancer by instillation of bacillus Calmette-Guérin (BCG) is highly recommended within certain groups of non-muscle-invasive stages but only partially effective. Toll-like receptors (TLRs) TLR4 and TLR9 likely mediate BCG effects by triggering innate systemic immune cell responses. In addition, TLR4 and TLR9 expressed in bladder cancer cells may contribute to the outcome of BCG treatment. Here, we studied the expression and function of TLR4 and TLR9 in human bladder cancer cell lines. TLR4 and TLR9 messenger RNA and protein levels were determined by real-time reverse transcription polymerase chain reaction and Western blot. Selected cell lines were analyzed with respect to cytokine induction, proliferation, and cell invasion after addition of BCG, TLR4-specific agonist lipopolysaccharide (LPS), or TLR9 agonist (CpG-oligodeoxynucleotide [ODN]). TLR4 and TLR9 were expressed quite heterogeneously in human bladder cancer cells. BCG caused induction of interleukin (IL)-6 or IL-8 in BFTC905 and T24 cells as representatives for TLR4-/TLR9-expressing cells. The study aimed to dissect TLR4- and TLR9-mediated effects. For functional analysis of TLR4 with LPS, we selected T24 and BFTC905 cells with high and undetectable TLR4 levels, respectively. For TLR9 analysis with CpG-ODN, we selected UMUC3 and RT112 cells with high and low TLR9 levels, respectively. Addition of LPS caused significant induction of TNFα and IL-6 messenger RNA in T24 cells but not in BFTC905 cells. Addition of CpG-ODN induced interferon ß (INFß), IL-8, tumor necrosis factor α (TNFα) and the angiogenic factors vascular endothelial growth factor-A and placental growth factor in UMUC3 cells; whereas in RT112 cells, induction of IL-8 and TNFα was noticed. Interestingly, addition of CpG-ODN significantly reduced cell viability and increased cell invasion in UMUC3 and RT112 cells. Our findings demonstrate that bladder cancer cell lines express functional TLR4 and TLR9 with

  11. TGF-β1 promotes the migration and invasion of bladder carcinoma cells by increasing fascin1 expression.

    Science.gov (United States)

    Zhang, Naiwen; Bi, Xiaojun; Zeng, Yu; Zhu, Yuyan; Zhang, Zhe; Liu, Yang; Wang, Jianfeng; Li, Xuejie; Bi, Jianbin; Kong, Chuize

    2016-08-01

    Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine that is reported to regulate cellular motility and invasive capability during tumor progression. Fascin1, an actin-bundling protein, increases cell motility, migration and adhesion. To investigate the function of TGF-β1 and test whether fascin1 is an important mediator of the tumor response to TGF-β1 in bladder carcinoma cells, real-time RT-PCR and western blot analysis were used to test changes in fascin1 expression after TGF-β1 (10 ng/ml) treatment in T24 and BIU87 cells. Small interfering RNA (siRNA) technique was performed to silence fascin1. Cell viability and biological behavior changes were evaluated by cell growth (MTT), wound-healing and Matrigel invasion assays. In the present study, we found that the mRNA and protein levels of fascin1 in the T24 and BIU87 cells were significantly increased after 10 ng/ml TGF-β1 treatment (pTGF-β1. The findings suggested that TGF-β1 can promote invasion and migration of T24 and BIU87 bladder carcinoma cells, and the increase in fascin1 expression may be the key point of this impact of TGF-β1.

  12. The src-family kinase inhibitor PP2 suppresses the in vitro invasive phenotype of bladder carcinoma cells via modulation of Akt.

    Science.gov (United States)

    Chiang, George J; Billmeyer, Brian R; Canes, David; Stoffel, John; Moinzadeh, Alireza; Austin, Christina A; Kosakowski, Monika; Rieger-Christ, Kimberly M; Libertino, John A; Summerhayes, Ian C

    2005-08-01

    To evaluate PP2 as a modulator of the cadherin/catenin complex in late-stage bladder carcinoma cells, and to assess its potential invasion-suppressor activity in this model. A panel of five human bladder carcinoma cells, characterizing late-stage disease, was used to determine the concentration for 50% inhibition of PP2 in cell-proliferation assays. Modulation of cadherin/catenin expression by PP2 was determined in Western blot analysis, with an assessment of the activation status of mitogen-activated protein kinase and Akt signalling pathways. Altered invasive capacity linked to these variables was determined in standard in vitro invasion assays. PP2 elicited concentration-dependent growth inhibition in all bladder cell lines within the panel, with growth suppression recorded at 10-35 micromol/L PP2. Distinct morphological changes were recorded in cell lines exposed to PP2, accompanied by up-regulation of plakoglobin expression in a subset of lines. Exposure of cells to PP2 resulted in inactivation of Akt in all cells and a concomitant reduction in in vitro invasive capacity. These results show that PP2 inhibits bladder carcinoma cell growth and can modulate plakoglobin expression in a subset of cell lines. In addition, PP2 can suppress the in vitro invasive capacity of bladder carcinoma cells by modulating the activation status of Akt.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-12-01

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

  14. Concomitant radiochemotherapy with 5-FU and cisplatin for invasive bladder cancer. Acute toxicity and first results

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    Birkenhake, S.; Leykamm, S.; Sauer, R. [Friedrich-Alexander Univ., Erlangen-Nuernberg (Germany). Dept. of Radiooncology; Martus, P. [Friedrich-Alexander Univ., Erlangen-Nuernberg (Germany). Dept. of Medical Statistics

    1999-03-01

    Purpose: To evaluate acute toxicity and efficacy of simultaneous radiochemotherapy for invasive urothelial cancer of the bladder. Patients and Methods: From September 1993 to July 1997, 61 patients with invasive bladder cancer were treated with a transurethral resection (TURB) followed by radiochemotherapy (RCT). Twenty-five received a combination of 5-FU and cisplatin. The prescribed doses were 600 mg/m{sup 2} 5-FU daily as continuous infusion over 5 days each in the 1st and 5th treatment week and 20 mg/m{sup 2} cisplatin daily at the same days as a short infusion. The pelvis was irradiated with 54 Gy, the bladder with 59.4 Gy and the paraortic nodes in 7 cases with 45 Gy, respectively. Six to 8 weeks after RCT a second TURB was performed for reasons of restaging. Results: Twenty out of 25 patients received at least 80% of the prescribed chemotherapy, in 13 cases the full dose could be given. Gastrointestinal toxicity of Grade I and II occurred in 10 cases, 1 patient developed severe diarrhea (Grade VI). After the 1st course of chemotherapy 7 patients had leuco- or thrombopenia of Grade III. One patient had a leucopenia of Grade IV. After the 2nd course 4 patients developed Grade III leuko- and thrombopenia, 1 of Grade IV. Two Grade II anemia were found. All more severe toxicities and necessary dose reductions were related to radiation of the paraaortic nodes. No life threatening infections, bleedings or cardiotoxicity was found. Restaging TURBs resulted in 22 complete remissions, 1 patient had a de-novo-carcinoma (Tis) at this time, 2 were non-responders (8%). After a median follow-up of 38 months 20 patients are alive (80%). Conclusions: 1. If irradiation of paraaortic nodes is necessary, 5-FU should not be applied, because the gastrointestinal toxicity is too extensive. In all other cases side effects are tolerable and can be managed by supportive care. 2. The first results are promising and should be evaluated in a prospective study. (orig.) [Deutsch

  15. Oncologic Outcomes after Anterior Exenteration for Muscle Invasive Bladder Cancer in Women

    DEFF Research Database (Denmark)

    Gregg, Justin R; Emeruwa, Curran; Wong, Johnson;

    2016-01-01

    PURPOSE: We investigated oncologic and urinary outcomes after anterior exenteration for urothelial cell carcinoma in females, identifying tumor characteristics associated with female pelvic organ involvement. We hypothesized that a lack of trigonal or bladder floor tumor, intraoperative palpable ...

  16. Examining Sexual Dysfunction in Non‐Muscle‐Invasive Bladder Cancer: Results of Cross‐Sectional Mixed‐Methods Research

    Directory of Open Access Journals (Sweden)

    Marc A. Kowalkowski, PhD

    2014-08-01

    Conclusions: Survivors' sexual symptoms may result from NMIBC, comorbidities, or both. These results inform literature and practice by raising awareness about the frequency of symptoms and the impact on NMIBC survivors' intimate relationships. Further work is needed to design symptom management education programs to dispel misinformation about contamination post‐treatment and improve quality of life. Kowalkowski MA, Chandrashekar A, Amiel GE, Lerner SP, Wittmann DA, Latini DM, and Goltz HH. Examining sexual dysfunction in non‐muscle‐invasive bladder cancer: Results of cross‐sectional mixed‐methods research. Sex Med 2014;2:141–151.

  17. Applicability of the EORTC risk tables to predict outcomes in non-muscle-invasive bladder cancer in Turkish patients.

    Science.gov (United States)

    Kılınç, Muhammet Fatih; Bayar, Göksel; Dalkılıç, Ayhan; Sönmez, Nurettin Cem; Arısan, Serdar; Güney, Soner

    2017-03-01

    To evaluate the consistency of the results of patients who were treated for non-muscle-invasive bladder cancer (NMIBC) in our clinic with the European Organization for Research and Treatment of Cancer (EORTC) risk table. Data were retrospectively analyzed from 452 patients who had undergone transurethral resection of bladder tumor (TUR-BT) between the years 2002, and 2010 for primary or recurrent NMIBC. Our study had a retrospective design but based on prospective cohort study. Patients were staged according to the 2002 Tumor Node Metastasis (TNM) classification and the 1973 World Health Organization grading system. Recurrence was defined as non-muscle-invasive or muscle-invasive and progression as muscle-invasive tumor determined based on following cystoscopy and TUR-BT results, and confirmed by histopathologic analysis. Patients in the current study were classified into four groups according to the EORTC risk tables. Time to first recurrence and progression was determined for each risk group. Of the 452 patients, 348 were enrolled in this study. The overall mean follow-up period was 55.25 months of all patients. Of 348 patients, 130 (37.4%) and 258 patients (74.1%) had recurrence after treatment at the 1 and 5 year follow-up period, respectively. While 35 (10.1%) and 99 patients (28.4%) progressed to muscle-invasive cancer at the 1 and 5 year follow-up period, respectively. In the multivariate analysis, grade, number, size of the tumor size, and concomitant carcinoma in situ were found to be statistically significant for disease progression and recurrence. When EORTC risk tables were comparatively evaluated in our patient population, we can say that EORTC tables predict nearly accurately the clinical course of patients with NMIBC.

  18. EFFICACY OF DIFFERENT RESECTIONS ON NON-MUSCLE-INVASIVE BLADDER CANCER AND ANALYSIS OF THE OPTIMAL SURGICAL METHOD.

    Science.gov (United States)

    Chen, G F; Shi, T P; Wang, B J; Wang, X Y; Zang, Q

    2015-01-01

    This study aimed to analyze the clinical efficacy of different resections in treating non-muscle-invasive bladder cancer (NMIBC), including partial cystectomy, transurethral resection of bladder tumor (TURBT) and holmium laser resection of bladder tumor. Two hundred and sixteen patients were recruited with NMIBC who were available for follow-up visits in hospital, including 62 cases treated with partial cystectomy, 90 cases treated with TURBT and 64 cases with holmium laser resection. Analysis was made on the cases with tumor relapse in the two years, on operation time, blood loss, time for indwelling urinary catheter, hospital stay and complications after operation. Results were compared to the clinical efficacy of these operation patterns. It was found that the two-year relapse rate for TURBT group, partial cystectomy group and Holmium laser resection group was 41%, 31%, and 33% respectively, and the difference had no statistical significance (p>0.05). Both the TURBT group and holmium laser resection group had shorter operation time, hospital stay and time for indwelling urinary catheter as well as much less blood loss when compared with the partial cystectomy group; the difference had statistical significance (pspasm. Therefore, this study presumes that holmium laser resection and TURBT are much safer and quicker for recovery and obviously superior to the partial cystectomy.

  19. Adjuvant radiotherapy after radical cystectomy for muscle-invasive bladder cancer: A retrospective multicenter study

    Science.gov (United States)

    Orré, Mathieu; Latorzeff, Igor; Fléchon, Aude; Roubaud, Guilhem; Brouste, Véronique; Gaston, Richard; Piéchaud, Thierry; Richaud, Pierre; Chapet, Olivier

    2017-01-01

    Objectives Radical cystectomy (RC) and pelvic lymph-node dissection (LND) is standard treatment for non-metastatic muscle-invasive urothelial bladder cancer (MIBC). However, loco-regional recurrence (LRR) is a common early event associated with poor prognosis. We evaluate 3-year LRR-free (LRRFS), metastasis-free (MFS) and overall survivals (OS) after adjuvant radiotherapy (RT) for pathological high-risk MIBC. Material and methods We retrospectively reviewed data from patients in 3 institutions. Inclusion criteria were MIBC, histologically-proven urothelial carcinoma treated by RC and adjuvant RT. Patients with conservative surgery were excluded. Outcomes were evaluated by Kaplan-Meier method. Acute toxicities were recorded according to CTCAE V4.0 scale. Results Between 2000 and 2013, 57 patients [median age 66.3 years (45–84)] were included. Post-operative pathological staging was ≤pT2, pT3 and pT4 in 16%, 44%, and 39%, respectively. PLND revealed 28% pN0, 26% pN1 and 42% pN2. Median number of lymph-nodes retrieved was 10 (2–33). Forty-eight patients (84%) received platin-based chemotherapy. For RT, clinical target volume 1 (CTV 1) encompassed pelvic lymph nodes for all patients. CTV 1 also included cystectomy bed for 37 patients (65%). CTV 1 median dose was 45 Gy (4–50). A boost of 16 Gy (5–22), corresponding to CTV 2, was administered for 30 patients, depending on pathological features. One third of patients received intensity-modulated RT. With median follow-up of 40.4 months, 8 patients (14%) had LRR. Three-year LRRFS, MFS and OS were 45% (95%CI 30–60), 37% (95%CI 24–51) and 49% (95%CI 33–63), respectively. Five (9%) patients had acute grade ≥3 toxicities (gastro-intestinal, genito-urinary and biological parameters). One patient died with intestinal fistula in a septic context. Conclusions Because of poor prognosis, an effective post-operative standard of care is needed for pathological high-risk MIBC. Adjuvant RT is feasible and may have

  20. Effects of Gene Tranfection with CH50 Polypeptide on the Invasion Ability of Bladder Cancer Cell Line BIU-87

    Institute of Scientific and Technical Information of China (English)

    WU Zhuang; CHEN Zhong; YE Zhangqun; ZHANG Jianhua; YE Shiqiao; ZHANG Guimei; FENG Zuohua

    2005-01-01

    Summary: The expression of CH50 polypoptide in bladder cancer cell line BIU-87 and the effects on the invasion ability of BIU-87 were investigated. The eukaryotic expressing vector pCH510 of polypeptide CH50 was introduced into BIU-87 cells by gene transfection in vitro. The expression of CH50 polypeptide was detected by using immunohistochemical S-P method. The expression of the transfected gene was identified by RT-PCR. Cell invasion assay kit was applied to detect the effect of CH50 polypeptide on the invasion ability of BIU-87. The results showed that the BIU-87 cells transfected with pCH510 could express the CH50 polypeptide, while in the control group, no CH50 polypeptide was detectable. In the transfection group, the invasion ability of BIU-87 in vitro was lower than in control group (P<0.05). It was concluded that CH50 polypeptide was successfully expressed in BIU-87 cells by gene transfection, by which the in vitro invasion ability of BIU-87 was inhibited.

  1. The role of neutrophils and TNF-related apoptosis-inducing ligand (TRAIL) in bacillus Calmette-Guérin (BCG) immunotherapy for urothelial carcinoma of the bladder.

    Science.gov (United States)

    Rosevear, Henry M; Lightfoot, Andrew J; O'Donnell, Michael A; Griffith, Thomas S

    2009-12-01

    Intravesical Mycobacterium bovis bacillus Calmette-Guérin (BCG) immunotherapy is a highly effective treatment for carcinoma in situ of the bladder, as well as high-risk nonmuscle invasive urothelial carcinoma of the bladder. Despite over 30 years of clinical experience with BCG, the therapy's mechanism has remained enigmatic. Observations regarding the role of neutrophils in BCG immunotherapy have led to exciting discoveries regarding the potential role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in creating the therapeutic benefit of BCG immunotherapy. In this paper, we will review the scope of the disease, highlight our understanding of the role for BCG in urothelial carcinoma of the bladder, explain the recent discoveries regarding the role of neutrophils and TRAIL in therapy, and theorize on potential future areas of research.

  2. The influence of the level of lamina propria invasion and the prevalence of p53 nuclear accumulation on survival in stage T1 transitional cell bladder cancer

    DEFF Research Database (Denmark)

    Hermann, G G; Horn, T; Steven, K

    1998-01-01

    related to age, level of lamina propria invasion and presence of p53 nuclear accumulation. For this subpopulation overall survival was 67%, and 79% for stage T1a, 70% for stage T1b and 57% for stage T1c (p positive (61......PURPOSE: We assessed the influence of the level of lamina propria invasion and the prevalence of p53 nuclear immunoreactivity on the survival of patients with stage T1 transitional cell bladder cancer. MATERIALS AND METHODS: All patients presenting with stage T1 bladder cancer were prospectively...... and routinely grouped according to the level of lamina propria invasion. Invasion of the tumor stalk was defined as stage T1a, invasion of the lamina propria proper superficial to the level of muscularis mucosa as stage T1b and into or deeper than the muscularis mucosa as stage T1c. The p53 nuclear...

  3. Luteolin decreases the attachment, invasion and cytotoxicity of UPEC in bladder epithelial cells and inhibits UPEC biofilm formation.

    Science.gov (United States)

    Shen, Xiao-fei; Ren, Lai-bin; Teng, Yan; Zheng, Shuang; Yang, Xiao-long; Guo, Xiao-juan; Wang, Xin-yuan; Sha, Kai-hui; Li, Na; Xu, Guang-ya; Tian, Han-wen; Wang, Xiao-ying; Liu, Xiao-kang; Li, Jingyu; Huang, Ning

    2014-10-01

    Urinary tract infection (UTI), primarily caused by uropathogenic Escherichia coli (UPEC), is one of the most common infectious diseases worldwide. Emerging antibiotic resistance requires novel treatment strategies. Luteolin, a dietary polyphenolic flavonoid, has been confirmed as a potential antimicrobial agent. Here, we evaluated the sub-MICs of luteolin for potential properties to modulate the UPEC infection. We found that luteolin significantly decreased the attachment and invasion of UPEC J96 or CFT073 in human bladder epithelial cell lines T24. Meanwhile, obvious decreased expression of type 1 fimbriae adhesin fimH gene, lower bacterial surface hydrophobicity and swimming motility, were observed in luteolin-pretreated UPEC. Furthermore, luteolin could attenuate UPEC-induced cytotoxicity in T24 cells, which manifested as decreased activity of lactate dehydrogenase (LDH). Simultaneously, the inhibition of luteolin on UPEC-induced cytotoxicity was confirmed by ethidium bromide/acridine orange staining. Finally, the luteolin-pretreated UPEC showed a lower ability of biofilm formation. Collectively, these results indicated that luteolin decreased the attachment and invasion of UPEC in bladder epithelial cells, attenuated UPEC-induced cytotoxicity and biofilm formation via down-regulating the expression of adhesin fimH gene, reducing the bacterial surface hydrophobicity and motility.

  4. Key signaling pathways in the muscle-invasive bladder carcinoma: Clinical markers for disease modeling and optimized treatment.

    Science.gov (United States)

    Kiselyov, Alex; Bunimovich-Mendrazitsky, Svetlana; Startsev, Vladimir

    2016-06-01

    In this review, we evaluate key molecular pathways and markers of muscle-invasive bladder cancer (MIBC). Overexpression and activation of EGFR, p63, and EMT genes are suggestive of basal MIBC subtype generally responsive to chemotherapy. Alterations in PPARγ, ERBB2/3, and FGFR3 gene products and their signaling along with deregulated p53, cytokeratins KRT5/6/14 in combination with the cellular proliferation (Ki-67), and cell cycle markers (p16) indicate the need for more radical treatment protocols. Similarly, the "bell-shape" dynamics of Shh expression levels may suggest aggressive MIBC. A panel of diverse biological markers may be suitable for simulation studies of MIBC and development of an optimized treatment protocol. We conducted a critical evaluation of PubMed/Medline and SciFinder databases related to MIBC covering the period 2009-2015. The free-text search was extended by adding the following keywords and phrases: bladder cancer, metastatic, muscle-invasive, basal, luminal, epithelial-to-mesenchymal transition, cancer stem cell, mutations, immune response, signaling, biological markers, molecular markers, mathematical models, simulation, epigenetics, transmembrane, transcription factor, kinase, predictor, prognosis. The resulting selection of ca 500 abstracts was further analyzed in order to select the latest publications relevant to MIBC molecular markers of immediate clinical significance. © 2015 UICC.

  5. MicroRNA-106a suppresses proliferation, migration, and invasion of bladder cancer cells by modulating MAPK signaling, cell cycle regulators, and Ets-1-mediated MMP-2 expression.

    Science.gov (United States)

    Shin, Seung-Shick; Park, Sung-Soo; Hwang, Byungdoo; Kim, Won Tae; Choi, Yung Hyun; Kim, Wun-Jae; Moon, Sung-Kwon

    2016-10-01

    Despite the clinical significance of tumorigenesis, little is known about the cellular signaling networks of microRNAs (miRs). Here we report a new finding that mir‑106a regulates the proliferation, migration, and invasion of bladder cancer cells. Basal expression levels of mir‑106a were significantly lower in bladder cancer cells than in normal urothelial cells. Overexpression of mir‑106a suppressed the proliferation of bladder cancer cell line EJ. Transient transfection of mir‑106a into EJ cells led to downregulation of ERK phosphorylation and upregulation of p38 and JNK phosphorylation over their levels in the control. Flow cytometry analysis revealed that mir‑106a-transfected cells accumulated in the G1-phase of the cell cycle, and cyclin D1 and CDK6 were significantly downregulated. This G1-phase cell cycle arrest was due in part to the upregulation of p21CIP1/WAF1. In addition, mir‑106a overexpression blocked the wound-healing migration and invasion of EJ cells. Furthermore, mir‑106a transfection resulted in decreased expression of MMP-2 and diminished binding activity of transcription factor Ets-1 in EJ cells. Collectively, we report the novel mir‑106a-mediated molecular signaling networks that regulate the proliferation, migration, and invasion of bladder cancer cells, suggesting that mir‑106a may be a therapeutic target for treating advanced bladder tumors.

  6. Role of Diffusion-Weighted Magnetic Resonance Imaging in Predicting Sensitivity to Chemoradiotherapy in Muscle-Invasive Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Soichiro [Department of Urology, Tokyo Medical and Dental University Graduate School, Tokyo (Japan); Koga, Fumitaka, E-mail: f-koga.uro@tmd.ac.jp [Department of Urology, Tokyo Medical and Dental University Graduate School, Tokyo (Japan); Kobayashi, Shuichiro [Department of Urology, Tokyo Medical and Dental University Graduate School, Tokyo (Japan); Ishii, Chikako; Tanaka, Hiroshi [Department of Radiology, Ochanomizu Surugadai Clinic, Tokyo (Japan); Tanaka, Hajime; Komai, Yoshinobu; Saito, Kazutaka; Masuda, Hitoshi; Fujii, Yasuhisa; Kawakami, Satoru; Kihara, Kazunori [Department of Urology, Tokyo Medical and Dental University Graduate School, Tokyo (Japan)

    2012-05-01

    Purpose: In chemoradiation (CRT)-based bladder-sparing approaches for muscle invasive bladder cancer (MIBC), patients who respond favorably to induction CRT enjoy the benefits of bladder preservation, whereas nonresponders do not. Thus, accurate prediction of CRT sensitivity would optimize patient selection for bladder-sparing protocols. Diffusion-weighted MRI (DW-MRI) is a functional imaging technique that quantifies the diffusion of water molecules in a noninvasive manner. We investigated whether DW-MRI predicts CRT sensitivity of MIBC. Methods and Materials: The study cohort consisted of 23 MIBC patients (cT2/T3 = 7/16) who underwent induction CRT consisting of radiotherapy to the small pelvis (40 Gy) with two cycles of cisplatin (20 mg/day for 5 days), followed by partial or radical cystectomy. All patients underwent DW-MRI before the initiation of treatment. Associations of apparent diffusion coefficient (ADC) values with CRT sensitivity were analyzed. The proliferative potential of MIBC was also assessed by analyzing the Ki-67 labeling index (LI) in pretherapeutic biopsy specimens. Results: Thirteen patients (57%) achieved pathologic complete response (pCR) to CRT. These CRT-sensitive MIBCs showed significantly lower ADC values (median, 0.63 Multiplication-Sign 10{sup -3} mm{sup 2}/s; range, 0.43-0.77) than CRT-resistant (no pCR) MIBCs (median, 0.84 Multiplication-Sign 10{sup -3} mm{sup 2}/s; range, 0.69-1.09; p = 0.0003). Multivariate analysis identified ADC value as the only significant and independent predictor of CRT sensitivity (p < 0.0001; odds ratio per 0.001 Multiplication-Sign 10{sup -3} mm{sup 2}/s increase, 1.03; 95% confidence interval, 1.01-1.08). With a cutoff ADC value at 0.74 Multiplication-Sign 10{sup -3} mm{sup 2}/s, sensitivity/specificity/accuracy in predicting CRT sensitivity was 92/90/91%. Ki-67 LI was significantly higher in CRT-sensitive MIBCs (p = 0.0005) and significantly and inversely correlated with ADC values ({rho} = -0.67, p = 0

  7. Targeting MACC1 by RNA interference inhibits proliferation and invasion of bladder urothelial carcinoma in T24 cells.

    Science.gov (United States)

    Xu, Song-Tao; Ding, Xiang; Ni, Qing-Feng; Jin, Shao-Ju

    2015-01-01

    The purpose of this article is to research on whether MACC1 can serve as a potential target for gene therapy of human bladder urothelial carcinoma (BUC). In this study, the expression of MACC1 gene was knocked down by RNA interference (RNAi) in the T24 cell (human BUC cell). The transcription level of MACC1 was detected by RT-PCR. Activities of MACC1, caspase-3, caspase-8, Bax and Met (mesenchymal-epithelial transition factor) protein were measured by Western blot. The cell proliferation and apoptosis were detected by MTT and flow cytometry. The cell's invasion ability was performed on Matrigel transwell assay. We also detect MMP2 (metalloproteinase-2) proteins by ELISA. The results showed that the level of MACC1 mRNA and protein was significantly reduced after RNAi. MTT assay showed that the proliferation of T24 cell was decreased due to RNA interference. Apoptosis studies also showed that MACC1 gene interference in T24 loses its anti-apoptotic effects. The expression of apoptosis proteins (Caspase-3, Caspase-8 and Bax) increased significantly due to the MACC1 RNAi. The level of Met protein was down-regulated obviously due to RNAi. Transwell assay showed that invasion abilities of T24 cells were reduced obviously due to MACC1 RNAi. Further studies showed that the secretion of MMP-2 was reduced by RNAi. It can conclude that the ability of proliferation and invasion in T24 cells can be inhibited by RNAi-targeting MACC1. As a result, MACC1 can serve as a potential target for gene therapy of human bladder urothelial carcinoma.

  8. 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.

  9. Bladder Carcinoma Data with Clinical Risk Factors and Molecular Markers: A Cluster Analysis

    Directory of Open Access Journals (Sweden)

    Enrique Redondo-Gonzalez

    2015-01-01

    Full Text Available Bladder cancer occurs in the epithelial lining of the urinary bladder and is amongst the most common types of cancer in humans, killing thousands of people a year. This paper is based on the hypothesis that the use of clinical and histopathological data together with information about the concentration of various molecular markers in patients is useful for the prediction of outcomes and the design of treatments of nonmuscle invasive bladder carcinoma (NMIBC. A population of 45 patients with a new diagnosis of NMIBC was selected. Patients with benign prostatic hyperplasia (BPH, muscle invasive bladder carcinoma (MIBC, carcinoma in situ (CIS, and NMIBC recurrent tumors were not included due to their different clinical behavior. Clinical history was obtained by means of anamnesis and physical examination, and preoperative imaging and urine cytology were carried out for all patients. Then, patients underwent conventional transurethral resection (TURBT and some proteomic analyses quantified the biomarkers (p53, neu, and EGFR. A postoperative follow-up was performed to detect relapse and progression. Clusterings were performed to find groups with clinical, molecular markers, histopathological prognostic factors, and statistics about recurrence, progression, and overall survival of patients with NMIBC. Four groups were found according to tumor sizes, risk of relapse or progression, and biological behavior. Outlier patients were also detected and categorized according to their clinical characters and biological behavior.

  10. Therapeutic Options in High-risk Non-muscle-invasive Bladder Cancer During the Current Worldwide Shortage of Bacille Calmette-Guerin

    NARCIS (Netherlands)

    Mostafid, A.H.; Redorta, J. Palou; Sylvester, R.; Witjes, J.A.

    2015-01-01

    Optimal management of high-risk non-muscle-invasive bladder cancer during the current bacillus Calmette-Guerin (BCG) shortage is challenging. Although no evidence-based guidelines exist for this specific situation, current management options can be adapted for when BCG supplies are limited or when

  11. Hexaminolevulinate blue-light cystoscopy in non-muscle-invasive bladder cancer: review of the clinical evidence and consensus statement on appropriate use in the USA

    NARCIS (Netherlands)

    Daneshmand, S.; Schuckman, A.K.; Bochner, B.H.; Cookson, M.S.; Downs, T.M.; Gomella, L.G.; Grossman, H.B.; Kamat, A.M.; Konety, B.R.; Lee, C.T.; Pohar, K.S.; Pruthi, R.S.; Resnick, M.J.; Smith, N.D.; Witjes, J.A.; Schoenberg, M.P.; Steinberg, G.D.

    2014-01-01

    Hexaminolevulinate (HAL) is a tumour photosensitizer that is used in combination with blue-light cystoscopy (BLC) as an adjunct to white-light cystoscopy (WLC) in the diagnosis and management of non-muscle-invasive bladder cancer (NMIBC). Since being licensed in Europe in 2005, HAL has been used in

  12. Neoadjuvant induction dose-dense MVAC for muscle invasive bladder cancer : efficacy and safety compared with classic MVAC and gemcitabine/cisplatin

    NARCIS (Netherlands)

    van de Putte, Elisabeth E Fransen; Mertens, Laura S.; Meijer, Richard P.; van der Heijden, Michiel S.; Bex, Axel; van der Poel, Henk G.; Kerst, J. Martijn; Bergman, Andries M.; Horenblas, Simon; van Rhijn, Bas W G

    2016-01-01

    Purpose: To investigate the efficacy and safety of neoadjuvant induction dose-dense MVAC (dd-MVAC) for muscle invasive bladder cancer (MIBC). Results of the 2-week-per-cycle regimen were compared with classic MVAC (4 weeks per cycle) and gemcitabine/cisplatin (GC, 3 weeks per cycle). Methods: We inc

  13. BCG and the treatment of superficial bladder cancer.

    Science.gov (United States)

    Moss, J T; Kadmon, D

    1991-12-01

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

  14. The natural history of symptoms and distress in patients and families following cystectomy for treatment of muscle invasive bladder cancer.

    Science.gov (United States)

    Benner, Carly; Greenberg, Molly; Shepard, Nancy; Meng, Maxwell V; Rabow, Michael W

    2014-04-01

    We characterized the natural history of symptoms with time in patients with bladder cancer undergoing cystectomy. For 6 months we followed 33 participants treated with muscle invasive bladder cancer treatment with cystectomy in this prospective cohort study. Patients and family caregivers completed validated symptom assessment and satisfaction surveys at baseline, and 2, 4 and 6 months later. Primary outcomes were the change from baseline in pain, fatigue, depression, anxiety, quality of life and spiritual well-being. Secondary outcomes included posttraumatic growth, patient satisfaction and family caregiver burden. Pain increased after radical cystectomy and remained increased 6 months postoperatively based on Brief Pain Inventory scores (baseline and 6-month scores 4.0, 95% CI 0-8.0 and 9.8, 95% CI 1.9-17.6, respectively, p = 0.03). Posttraumatic growth showed a trend toward an increase at 2 months (p = 0.06). Fatigue peaked at 4 months but did not change significantly with time (p = 0.12). There was similarly no significant change with time in depression, anxiety, quality of life, spiritual well-being or satisfaction. Neither family caregiver burden nor satisfaction showed a statistically significant change with time postoperatively. Pain increased after radical cystectomy and remained increased 6 months postoperatively. There was a trend toward increased posttraumatic growth at 2 months. Otherwise, by 6 months cystectomy was associated with no improvement in preoperative symptoms of fatigue, quality of life, spiritual well-being, depression or anxiety. After cystectomy pain should be assessed and treated more aggressively in patients with bladder cancer and efforts should be made to improve postoperative symptoms. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  15. 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.

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

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

    2014-04-05

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

  17. PTTG1 regulated by miR-146a-3p promotes bladder cancer migration, invasion, metastasis and growth

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    Xiang, Wei; Wu, Xinchao; Huang, Chao; Wang, Miao; Zhao, Xian; Luo, Gang; Li, Yawei; Jiang, Guosong; Xiao, Xingyuan; Zeng, Fuqing

    2017-01-01

    Pituitary tumor-transforming gene 1 (PTTG1) is identified as an oncogene, and overexpresses in many tumors. However, the role of PTTG1 in bladder cancer (BC) hasn't yet been characterized well. In this study, we showed the expression of PTTG1 mRNA and protein were both significantly increased in BC tissues and cells. The PTTG1 protein levels were positive correlated with increased tumor size, tumor–node–metastasis (TNM) stage, lymphatic invasion and distant metastasis of BC. PTTG1 knockdown dramatically suppressed the migration, invasion, metastasis and growth, and induced senescence and cell-cycle arrest at G0/G1 phase of BC cells. We further identified PTTG1 was the direct target of miR-146a-3p through using target prediction algorithms and luciferase reporter assay. miR-146a-3p was low expressed and negatively correlated with PTTG1 levels in BC tissues and cells. miR-146a-3p overexpression inhibited migration, invasion, metastasis and growth, and induced senescence of BC cells. Rescue experiment suggested ectopic expression of miR-146a-3p and PTTG1 suppressed migration, invasion and induced cell cycle arrest and senescence of BC cells compared to PTTG1 overexpression, confirming miR-146a-3p inhibited BC progression by targeting PTTG1. In summary, our study found miR-146a-3p/PTTG1 axis regulated BC migration, invasion, metastasis and growth, and might be a targets for BC therapy. PMID:27893422

  18. GSTT1 as a Prognosticator for Recurrence and Progression in Patients with Non-Muscle-Invasive Bladder Cancer

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    Yun-Sok Ha

    2010-01-01

    Full Text Available Although polymorphisms in glutathione S-transferase (GST have been associated with the risk of bladder cancer (BC, few reports provide information about the development of BC. The aim of the present study was to investigate the effect of homozygous glutathione S-transferase-μ (GSTM1 and glutathione S-transferase-&phis; (GSTT1 deletions as prognostic markers in non-muscle-invasive bladder cancer (NMIBC. A total of 241 patients with primary NMIBC were enrolled in this study. GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR using blood genomic DNA. The results were compared with clinicopathological parameters. The prognostic significance of the GSTs was evaluated by Kaplan-Meier and multivariate Cox regression model. A statistically significant association between genotype and histopathological parameter was not observed. The patients with the GSTT1-positive genotype had significantly reduced recurrence- and progression-free survival than those with the GSTT1-null genotype (log-rank test, p < 0.05, respectively. Recurrenceand progressionfree survival were not related to the GSTM1 genotypes. In multivariate regression analysis, the GSTT1positive genotype was the independent predictor for recurrence [hazard ratio (HR, 1.631; p = 0.043] and progression (HR, 3.418; p = 0.006. These results suggested that the GSTT1 genotype could be a useful prognostic marker for recurrence and progression in NMIBC.

  19. Contemporary management of patients with high-risk non-muscle-invasive bladder cancer who fail intravesical BCG therapy.

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    Yates, D R; Rouprêt, M

    2011-08-01

    It is advocated that patients with high-risk non-muscle-invasive bladder cancer (NMIBC) receive an adjuvant course of intravesical Bacille Calmette-Guerin (BCG) as first-line treatment. However, a substantial proportion of patients will 'fail' BCG, either early with persistent (refractory) disease or recur late after a long disease-free interval (relapsing). Guideline recommendation in the 'refractory' setting is radical cystectomy, but there are situations when extirpative surgery is not feasible due to competing co-morbidity, a patient's desire for bladder preservation or reluctance to undergo surgery. In this review, we discuss the contemporary management of NMIBC in patients who have failed prior BCG and are not suitable for radical surgery and highlight the potential options available. These options can be categorised as immunotherapy, chemotherapy, device-assisted therapy and combination therapy. However, the current data are still inadequate to formulate definitive recommendations, and data from ongoing trials and maturing studies will give us an insight into whether there is a realistic efficacious second-line treatment for patients who fail intravesical BCG but are not candidates for definitive surgery.

  20. ROLE OF ADJUVANT INTRAVESICAL CHEMOTHERAPY IN THE COMBINED ORGAN-SPARING TREATMENT OF NON-MUSCLE-INVASIVE BLADDER CANCER

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    A. Yu. Zubko

    2014-01-01

    Full Text Available Objective: to enhance the efficiency of combined treatment for non-muscle-invasive bladder cancer ((NMIBC and to assess the results of its treatment using transurethral resection (TUR as monotherapy and in combination with intravesical adjuvant chemotherapy (CT.Subjects and methods. The results of treatment were analyzed in 59 patients with NMIBC. Twenty-two patients underwent TUR in Group 1; TUR and single intravesical injection of drugs were performed in 19 patients in Group 2; 18 patients had TUR and long-term intravesical CT.Results and discussion. The recurrence rates were 59.1, 57.9, and 38.89 % in Groups 1, 2, and 3, respectively. Intravesical CT was found to appreciably affect the prevention of recurrence in the area of resection. The rate of this recurrence was 31.81, 26.32, and 5.56 % in Groups 1, 2, and 3, respectively. Conclusion. Adjuvant intravesical chemotherapy CT is an effective method to prevent recurrent bladder cancer.

  1. Applications of chemotherapy in muscle invasive bladder cancer with bladder preservation%应重视化疗在肌层浸润性膀胱癌保留膀胱治疗中的作用

    Institute of Scientific and Technical Information of China (English)

    田野

    2014-01-01

    Chemotherapy has been developing to be an important adjuvant treatment methods in treatment of muscle invasive bladder cancer in recent years. Such method is meaningful for patients who want to preserve the bladder. The author summarized the role and effect of neoadjuvant chemotherapy and adjuvant chemotherapy. This article reviews the methods and effect of radical transurethral resection of bladder tumor with chemotherapy and partial cystectomy with chemotherapy. Data of several special patients including patients with renal transplantation and dialysis patients undergoing chemotherapy are presented. The problems existing in current drug sensitivity of chemotherapy are discussed finally. The future of chemotherapy in muscle invasive bladder cancer with bladder preservation is predicted.%化疗是近年来肌层浸润性膀胱癌重要的辅助治疗手段,对于临床要求保留膀胱的患者意义重大。本文介绍了新辅助化疗和辅助化疗的作用及效果,对经尿道根治性膀胱肿瘤切除术(transurethral resection of bladder tumor,TURBT)联合化疗以及膀胱部分切除术联合化疗的方法及疗效进行综述,同时对一些特殊患者例如肾脏移植患者及透析患者的化疗进行了介绍;最后对当前化疗中存在的药物敏感性问题加以阐述,并对今后化疗在肌层浸润性膀胱癌保留膀胱的发展前景进行了展望。

  2. Expression of RFC/SLC19A1 is associated with tumor type in bladder cancer patients.

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    Alyaa M Abdel-Haleem

    Full Text Available Urinary bladder cancer (UBC ranks ninth in worldwide cancer. In Egypt, the pattern of bladder cancer is unique in that both the transitional and squamous cell types prevail. Despite much research on the topic, it is still difficult to predict tumor progression, optimal therapy and clinical outcome. The reduced folate carrier (RFC/SLC19A1 is the major transport system for folates in mammalian cells and tissues. RFC is also the primary means of cellular uptake for antifolate cancer chemotherapeutic drugs, however, membrane transport of antifolates by RFC is considered as limiting to antitumor activity. The purpose of this study was to compare the mRNA expression level of RFC/SLC19A1 in urothelial and non-urothelial variants of bladder carcinomas. Quantification of RFC mRNA in the mucosa of 41 untreated bladder cancer patients was performed using RT-qPCR. RFC mRNA steady-state levels were ∼9-fold higher (N = 39; P<0.0001 in bladder tumor specimens relative to normal bladder mRNA. RFC upregulation was strongly correlated with tumor type (urothelial vs. non-urothelial; p<0.05 where median RFC mRNA expression was significantly (p<0.05 higher in the urothelial (∼14-fold compared to the non-urothelial (∼4-fold variant. This may account for the variation in response to antifolate-containing regimens used in the treatment of either type. RFC mRNA levels were not associated with tumor grade (I, II and III or stage (muscle-invasive vs. non-muscle invasive implying that RFC cannot be used for prognostic purposes in bladder carcinomas and its increased expression is an early event in human bladder tumors pathogenesis. Further, RFC can be considered as a potential marker for predicting response to antifolate chemotherapy in urothelial carcinomas.

  3. CCL21/CCR7 enhances the proliferation, migration, and invasion of human bladder cancer T24 cells.

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    Miao Mo

    Full Text Available To investigate the effects of CCL21/CCR7 on the proliferation, migration, and invasion of T24 cells and the possible associated mechanisms: expression of MMP-2 and MMP-9, and regulation of BCL-2 and BAX proteins.T24 cells received corresponding treatments including vehicle control, antibody (20 ng/mL CCR7 antibody and 50 ng/ml CCL21, and 50, 100, and 200 ng/ml CCL21. Proliferation was evaluated by MTT assay; cell migration and invasion were assayed using a transwell chamber. Cell apoptosis was induced by Adriamycin (ADM. The rate of cell apoptosis was examined by flow cytometry using annexin V-FITC/PI staining. Western-blot was used to analyze MMP-2 and MMP-9 and BCL-2 and BAX proteins.CCL21 promoted T24 cell proliferation in concentration-dependent manner with that 200 ng/mL induced the largest amount of proliferation. Significant differences of cell migration were found between CCL21treatment groups and the control group in both the migration and invasion studies (P < 0.001 for all. The expressions of MMP-2 and MMP-9 proteins were significantly increased after CCL21 treatment (p < 0.05 for all. Protein expression of Bcl-21 follows an ascending trend while the expression of Bax follows a descending trend as the concentration of CCL21 increases. No difference was found between the control group and antibody group for all assessments.CCL21/CCR7 promoted T24 cell proliferation and enhanced its migration and invasion via the increased expression of MMP-2 and MMP-9. CCL21/CCR7 had antiapoptotic activities on T24 cells via regulation of Bcl-2 and Bax proteins. CCL21/CCR7 may promote bladder cancer development and metastasis.

  4. 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

  5. Comparative Gene Expression Analyses Identify Luminal and Basal Subtypes of Canine Invasive Urothelial Carcinoma That Mimic Patterns in Human Invasive Bladder Cancer.

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    Deepika Dhawan

    Full Text Available More than 160,000 people are expected to die from invasive urothelial carcinoma (iUC this year worldwide. Research in relevant animal models is essential to improving iUC management. Naturally-occurring canine iUC closely resembles human iUC in histopathology, metastatic behavior, and treatment response, and could provide a relevant model for human iUC. The molecular characterization of canine iUC, however, has been limited. Work was conducted to compare gene expression array results between tissue samples from iUC and normal bladder in dogs, with comparison to similar expression array data from human iUC and normal bladder in the literature. Considerable similarities between enrichment patterns of genes in canine and human iUC were observed. These included patterns mirroring basal and luminal subtypes initially observed in human breast cancer and more recently noted in human iUC. Canine iUC samples also exhibited enrichment for genes involved in P53 pathways, as has been reported in human iUC. This is particularly relevant as drugs targeting these genes/pathways in other cancers could be repurposed to treat iUC, with dogs providing a model to optimize therapy. As part of the validation of the results and proof of principal for evaluating individualized targeted therapy, the overexpression of EGFR in canine bladder iUC was confirmed. The similarities in gene expression patterns between dogs and humans add considerably to the value of naturally-occurring canine iUC as a relevant and much needed animal model for human iUC. Furthermore, the finding of expression patterns that cross different pathologically-defined cancers could allow studies of dogs with iUC to help optimize cancer management across multiple cancer types. The work is also expected to lead to a better understanding of the biological importance of the gene expression patterns, and the potential application of the cross-species comparisons approach to other cancer types as well.

  6. Comparative Gene Expression Analyses Identify Luminal and Basal Subtypes of Canine Invasive Urothelial Carcinoma That Mimic Patterns in Human Invasive Bladder Cancer.

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    Dhawan, Deepika; Paoloni, Melissa; Shukradas, Shweta; Choudhury, Dipanwita Roy; Craig, Bruce A; Ramos-Vara, José A; Hahn, Noah; Bonney, Patty L; Khanna, Chand; Knapp, Deborah W

    2015-01-01

    More than 160,000 people are expected to die from invasive urothelial carcinoma (iUC) this year worldwide. Research in relevant animal models is essential to improving iUC management. Naturally-occurring canine iUC closely resembles human iUC in histopathology, metastatic behavior, and treatment response, and could provide a relevant model for human iUC. The molecular characterization of canine iUC, however, has been limited. Work was conducted to compare gene expression array results between tissue samples from iUC and normal bladder in dogs, with comparison to similar expression array data from human iUC and normal bladder in the literature. Considerable similarities between enrichment patterns of genes in canine and human iUC were observed. These included patterns mirroring basal and luminal subtypes initially observed in human breast cancer and more recently noted in human iUC. Canine iUC samples also exhibited enrichment for genes involved in P53 pathways, as has been reported in human iUC. This is particularly relevant as drugs targeting these genes/pathways in other cancers could be repurposed to treat iUC, with dogs providing a model to optimize therapy. As part of the validation of the results and proof of principal for evaluating individualized targeted therapy, the overexpression of EGFR in canine bladder iUC was confirmed. The similarities in gene expression patterns between dogs and humans add considerably to the value of naturally-occurring canine iUC as a relevant and much needed animal model for human iUC. Furthermore, the finding of expression patterns that cross different pathologically-defined cancers could allow studies of dogs with iUC to help optimize cancer management across multiple cancer types. The work is also expected to lead to a better understanding of the biological importance of the gene expression patterns, and the potential application of the cross-species comparisons approach to other cancer types as well.

  7. Prognostic Value of Beta-Tubulin-3 and c-Myc in Muscle Invasive Urothelial Carcinoma of the Bladder

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    Massari, Francesco; Bria, Emilio; Ciccarese, Chiara; Munari, Enrico; Modena, Alessandra; Zambonin, Valentina; Sperduti, Isabella; Artibani, Walter; Cheng, Liang; Martignoni, Guido; Tortora, Giampaolo; Brunelli, Matteo

    2015-01-01

    Background To date, putative prognostic biomarkers have shown limited utility from the clinical perspective for bladder urothelial carcinoma. Herein, the expression of beta-tubulin-3 and c-Myc was evaluated to determine their prognostic potential. Methods In formalin fixed-paraffin embedded blocks, immunohistochemical expression of c-Myc and beta-tubulin-3 was evaluated. H score ranging from 0 to 300 was obtained by multiplying the percentage of positive cells by intensity (0–3); c-Myc and beta-tubulin-3 expression was defined: 0: negative, 1: weakly positive, 2: strongly positive. Results beta-tubulin-3 and c-Myc immunoexpression was available for 46 cases. At the univariate analysis, node-involvement, beta-tubulin-3 and c-Myc overexpression discriminate shorter DFS (HR 2.19, p = 0.043; HR 3.10, p = 0.24 and HR 3.05, p = 0.011, respectively); 2-yrs DFS log-rank analysis according to low versus high level of immunoexpression were statistically significant; beta-tubulin-3, 53% low vs 12.7% high (p = value 0.02) and c-Myc 28 low vs 8 high (p-value 0.007). Patients displaying negative beta-tubulin-3/c-Myc had statistically significant better 2-yrs DFS than those with mixed expression or double positivity (54.5% versus 18.7% versus 0%, log-rank p = 0.006). Conclusions c-Myc and beta-tubulin-3 show improvement for prognostic risk stratification in patients with muscle invasive bladder urothelial carcinoma. These molecular pathways may also be candidate to improve predictiveness to targeted therapies. PMID:26046361

  8. Prognostic Value of Beta-Tubulin-3 and c-Myc in Muscle Invasive Urothelial Carcinoma of the Bladder.

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    Francesco Massari

    Full Text Available To date, putative prognostic biomarkers have shown limited utility from the clinical perspective for bladder urothelial carcinoma. Herein, the expression of beta-tubulin-3 and c-Myc was evaluated to determine their prognostic potential.In formalin fixed-paraffin embedded blocks, immunohistochemical expression of c-Myc and beta-tubulin-3 was evaluated. H score ranging from 0 to 300 was obtained by multiplying the percentage of positive cells by intensity (0-3; c-Myc and beta-tubulin-3 expression was defined: 0: negative, 1: weakly positive, 2: strongly positive.beta-tubulin-3 and c-Myc immunoexpression was available for 46 cases. At the univariate analysis, node-involvement, beta-tubulin-3 and c-Myc overexpression discriminate shorter DFS (HR 2.19, p = 0.043; HR 3.10, p = 0.24 and HR 3.05, p = 0.011, respectively; 2-yrs DFS log-rank analysis according to low versus high level of immunoexpression were statistically significant; beta-tubulin-3, 53% low vs 12.7% high (p = value 0.02 and c-Myc 28 low vs 8 high (p-value 0.007. Patients displaying negative beta-tubulin-3/c-Myc had statistically significant better 2-yrs DFS than those with mixed expression or double positivity (54.5% versus 18.7% versus 0%, log-rank p = 0.006.c-Myc and beta-tubulin-3 show improvement for prognostic risk stratification in patients with muscle invasive bladder urothelial carcinoma. These molecular pathways may also be candidate to improve predictiveness to targeted therapies.

  9. Prognostic significance of lymphovascular invasion in radical cystectomy on patients with bladder cancer: a systematic review and meta-analysis.

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    Hwanik Kim

    Full Text Available PURPOSE: The objective of the present study was to conduct a systematic review and meta-analysis of published literature to appraise the prognostic value of lymphovascular invasion (LVI in radical cystectomy specimens. MATERIALS AND METHODS: Following the PRISMA statement, PubMed, Cochrane Library, and SCOPUS database were searched from the respective dates of inception until June 2013. RESULTS: A total of 21 articles met the eligibility criteria for this systematic review, which included a total of 12,527 patients ranging from 57 to 4,257 per study. LVI was detected in 34.6% in radical cystectomy specimens. LVI was associated with higher pathological T stage and tumor grade, as well as lymph node metastasis. The pooled hazard ratio (HR was statistically significant for recurrence-free survival (pooled HR, 1.61; 95% confidence interval [CI], 1.26-2.06, cancer-specific survival (pooled HR, 1.67; 95% CI, 1.38-2.01, and overall survival (pooled HR, 1.67; 95% CI, 1.38-2.01, despite the heterogeneity among included studies. On sensitivity analysis, the pooled HRs and 95% CIs were not significantly altered when any one study was omitted. The funnel plot for overall survival demonstrated a certain degree of asymmetry, which showed slight publication bias. CONCLUSIONS: This meta-analysis indicates that LVI is significantly associated with poor outcome in patients with bladder cancer who underwent radical cystectomy. Adequately designed prospective studies are required to provide the precise prognostic significance of LVI in bladder cancer.

  10. Novel somatic mutations identified by whole-exome sequencing in muscle-invasive transitional cell carcinoma of the bladder.

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    Pan, Huixing; Xu, Xiaojian; Wu, Deyao; Qiu, Qiaocheng; Zhou, Shoujun; He, Xuefeng; Zhou, Yunfeng; Qu, Ping; Hou, Jianquan; He, Jun; Zhou, Jian

    2016-02-01

    Transitional cell carcinoma (TCC) is the one of the most commonly observed types of cancer globally. The identification of novel disease-associated genes in TCC has had a significant effect on the diagnosis and treatment of bladder cancer; however, there may be a large number of novel genes that have not been identified. In the present study, the exomes of two individuals who were diagnosed with muscle-invasive TCC (MI-TCC) were sequenced to investigate potential variants. Subsequently, following algorithm and filter analysis, Sanger sequencing was used to validate the results of deep sequencing. Immunohistochemistry (IHC) was employed to observe the differences in HECT, C2 and WW domain-containing E3 ubiquitin protein ligase 1 (HECW1) protein expression between tumor tissues and para-carcinoma tissues. A total of 6 nonsynonymous mutation genes were identified in MI-TCC, identified as copine VII, RNA binding motif protein, X-linked-like 3, acyl-CoA synthetase medium-chain family member 2A, HECW1, zinc finger protein 273 and trichohyalin. Furthermore, 5 cases were identified to possess a HECW1 gene mutation in 61 MI-TCC specimens, and all of these were point mutations located at exon 11 on chromosome 7. The mutation categories of HECW1 had 4 missense mutations and 1 nonsense mutation. IHC revealed that HECW1 protein was expressed at significantly increased levels in MI-TCC compared with normal bladder urothelium (PHECW1, which may possess a significant role in the pathogenesis of TCC.

  11. 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

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    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

  12. Abnormal Protein Glycosylation and Activated PI3K/Akt/mTOR Pathway: Role in Bladder Cancer Prognosis and Targeted Therapeutics

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    Lima, Luís; Peixoto, Andreia; Fernandes, Elisabete; Neves, Diogo; Neves, Manuel; Gaiteiro, Cristiana; Tavares, Ana; Gil da Costa, Rui M.; Cruz, Ricardo; Amaro, Teresina; Oliveira, Paula A.; Ferreira, José Alexandre; Santos, Lúcio L.

    2015-01-01

    Muscle invasive bladder cancer (MIBC, stage ≥T2) is generally associated with poor prognosis, constituting the second most common cause of death among genitourinary tumours. Due to high molecular heterogeneity significant variations in the natural history and disease outcome have been observed. This has also delayed the introduction of personalized therapeutics, making advanced stage bladder cancer almost an orphan disease in terms of treatment. Altered protein glycosylation translated by the expression of the sialyl-Tn antigen (STn) and its precursor Tn as well as the activation of the PI3K/Akt/mTOR pathway are cancer-associated events that may hold potential for patient stratification and guided therapy. Therefore, a retrospective design, 96 bladder tumours of different stages (Ta, T1-T4) was screened for STn and phosphorylated forms of Akt (pAkt), mTOR (pmTOR), S6 (pS6) and PTEN, related with the activation of the PI3K/Akt/mTOR pathway. In our series the expression of Tn was residual and was not linked to stage or outcome, while STn was statically higher in MIBC when compared to non-muscle invasive tumours (p = 0.001) and associated decreased cancer-specific survival (log rank p = 0.024). Conversely, PI3K/Akt/mTOR pathway intermediates showed an equal distribution between non-muscle invasive bladder cancer (NMIBC) and MIBC and did not associate with cancer-specif survival (CSS) in any of these groups. However, the overexpression of pAKT, pmTOR and/or pS6 allowed discriminating STn-positive advanced stage bladder tumours facing worst CSS (p = 0.027). Furthermore, multivariate Cox regression analysis revealed that overexpression of PI3K/Akt/mTOR pathway proteins in STn+ MIBC was independently associated with approximately 6-fold risk of death by cancer (p = 0.039). Mice bearing advanced stage chemically-induced bladder tumours mimicking the histological and molecular nature of human tumours were then administrated with mTOR-pathway inhibitor sirolimus (rapamycin

  13. Abnormal Protein Glycosylation and Activated PI3K/Akt/mTOR Pathway: Role in Bladder Cancer Prognosis and Targeted Therapeutics.

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    Costa, Céu; Pereira, Sofia; Lima, Luís; Peixoto, Andreia; Fernandes, Elisabete; Neves, Diogo; Neves, Manuel; Gaiteiro, Cristiana; Tavares, Ana; Gil da Costa, Rui M; Cruz, Ricardo; Amaro, Teresina; Oliveira, Paula A; Ferreira, José Alexandre; Santos, Lúcio L

    2015-01-01

    Muscle invasive bladder cancer (MIBC, stage ≥T2) is generally associated with poor prognosis, constituting the second most common cause of death among genitourinary tumours. Due to high molecular heterogeneity significant variations in the natural history and disease outcome have been observed. This has also delayed the introduction of personalized therapeutics, making advanced stage bladder cancer almost an orphan disease in terms of treatment. Altered protein glycosylation translated by the expression of the sialyl-Tn antigen (STn) and its precursor Tn as well as the activation of the PI3K/Akt/mTOR pathway are cancer-associated events that may hold potential for patient stratification and guided therapy. Therefore, a retrospective design, 96 bladder tumours of different stages (Ta, T1-T4) was screened for STn and phosphorylated forms of Akt (pAkt), mTOR (pmTOR), S6 (pS6) and PTEN, related with the activation of the PI3K/Akt/mTOR pathway. In our series the expression of Tn was residual and was not linked to stage or outcome, while STn was statically higher in MIBC when compared to non-muscle invasive tumours (p = 0.001) and associated decreased cancer-specific survival (log rank p = 0.024). Conversely, PI3K/Akt/mTOR pathway intermediates showed an equal distribution between non-muscle invasive bladder cancer (NMIBC) and MIBC and did not associate with cancer-specif survival (CSS) in any of these groups. However, the overexpression of pAKT, pmTOR and/or pS6 allowed discriminating STn-positive advanced stage bladder tumours facing worst CSS (p = 0.027). Furthermore, multivariate Cox regression analysis revealed that overexpression of PI3K/Akt/mTOR pathway proteins in STn+ MIBC was independently associated with approximately 6-fold risk of death by cancer (p = 0.039). Mice bearing advanced stage chemically-induced bladder tumours mimicking the histological and molecular nature of human tumours were then administrated with mTOR-pathway inhibitor sirolimus (rapamycin

  14. Practical use of perioperative chemotherapy for muscle-invasive bladder cancer: summary of session at the Society of Urologic Oncology annual meeting.

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    Apolo, Andrea B; Grossman, Herbert Barton; Bajorin, Dean; Steinberg, Gary; Kamat, Ashish M

    2012-01-01

    At the 11th annual meeting of the Society of Urologic Oncology, an expert panel was convened to discuss the practical use of perioperative chemotherapy for muscle-invasive bladder cancer. The discussion was structured as a case-based debate among the panelists. The topics included: neoadjuvant chemotherapy with a focus on T2 disease, pros and cons, survival data, tolerability of cisplatin-based therapy, can we avoid radical cystectomy in complete responders, limitations and alternatives to cisplatin-based therapy, management of 'suboptimal' chemotherapy, residual disease after neoadjuvant chemotherapy, adjuvant chemotherapy, and key aspects of radical cystectomy and lymph-node dissection in multimodal therapy. The presentations were derived from published literature. The panelists agreed that patients with muscle-invasive bladder cancer should be managed with a multidisciplinary team, including urologist and medical oncologist. Cisplatin-based neoadjuvant chemotherapy has demonstrated improved survival and should be incorporated into the management of all eligible patients with muscle-invasive bladder cancer. However, in some centers, neoadjuvant chemotherapy is reserved for patients with >T2 disease or high-risk features. There are no data for the administration of non-cisplatin-based neoadjuvant chemotherapy, such as carboplatin-combinations. Cisplatin-ineligible patients should proceed directly to surgical extirpation with adjuvant cisplatin-based chemotherapy considered based on pathologic findings. However, the data for adjuvant chemotherapy is less compelling. As our refinement of the selection process continues, we may be able to better identify subsets of patients who may be spared chemotherapy, but much work remains to be done in this arena. The current standard for muscle-invasive bladder cancer patients is cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy and pelvic lymph-node dissection.

  15. [Bilateral Granulomatous Renal Masses after Intravesical BCG Therapy for Non-muscle-invasive Bladder Cancer and Carcinoma in Situ of the Upper Urinary Tract: A Case Study].

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    Higashioka, Kazuhiko; Miyake, Noriko; Nishida, Ruriko; Chong, Yong; Shimoda, Shinji; Shimono, Nobuyuki

    2015-07-01

    Bacillus Calmette-Guèrin (BCG) is commonly used not only as an infant vaccination, but also as a treatment of and prophylaxis to prevent recurrence in the management of non-muscle-invasive bladder cancer. However, the use of "live" BCG is sometimes complicated by associated infection. We present a case study of a 77-year-old man who developed bilateral renal masses after intravesical BCG therapy was initiated in November 2013, following transurethral resection of non-muscle-invasive bladder cancer. After four courses of BCG (Japan strain, 80 mg per treatment) instillations, a computed tomography examination for febrile episodes showed multiple bilateral renal masses, accompanied by a histological finding of a granulomatous reaction. An acid fast bacterium was cultured from only urine among blood, urine, and microscopic samples. Using the cultured strain, BCG infection was confirmed by the specific gene deletion pattern based on allele-specific polymerase chain reaction analysis. Anti-tuberculosis treatment, including isoniazid (300 mg/day), rifampicin (600 mg/day), and ethambutol (1,000 mg/day), was started for the BCG-related renal granuloma in February 2014. After 3 months, antibiotic therapy was discontinued owing to severe appetite loss, though the masses remained solid. No rapid growth has been detected after anti-BCG therapy. Intravesical BCG therapy is recommended worldwide as one of standard treatments for non-muscle-invasive bladder cancer. We should closely observe patients undergoing this approach for emerging BCG complications.

  16. Constructing prognostic model incorporating the 2004 WHO/ISUP classification for patients with non-muscle-invasive urothelial tumours of the urinary bladder.

    Science.gov (United States)

    Pan, Chin-Chen; Chang, Yen-Hwa; Chen, Kuang-Kuo; Yu, Hui-Jung; Sun, Chih-Hao; Ho, Donald M T

    2010-10-01

    To construct a prognostic model for recurrence-free survival (RFS), progression-free survival (PFS) and cancer-specific survival (CSS) for patients who have undergone transurethral resection of non-muscle-invasive (pTa/pT1) urinary bladder urothelial tumours. 1366 patients who had undergone transurethral resection of primary non-muscle-invasive urothelial tumours (pTa, 891 patients; pT1, 475 patients) confined to the bladder were retrospectively studied. Tumours were classified according to the 2004 WHO/International Society of Urologic Pathology grading system. Kaplan-Meier and stepwise Cox regression models were applied, and 200 bootstrap resamples were used to generate survival estimates and 95% CIs. A nomogram was developed that incorporated significant variables predicting survival. RFS, PFS and CSS probabilities for non-muscle-invasive bladder urothelial tumours were calculated. Incorporating salient prognostic factors (tumour grade, pT stage, patient age, status of intravesical instillation), the model satisfactorily predicted PFS (concordance index=0.79) and CSS (concordance index=0.87). Robust nomograms were created to predict PFS and CSS. These data provide an overall perspective of disease outcomes which may aid in developing individualised follow-up programmes.

  17. LDH-A promotes malignant progression via activation of epithelial-to-mesenchymal transition and conferring stemness in muscle-invasive bladder cancer.

    Science.gov (United States)

    Jiang, Fujin; Ma, Song; Xue, Yubao; Hou, Jianquan; Zhang, Yongjie

    2016-01-22

    Lactate dehydrogenase-A(LDH-A) is an important rate-limiting enzyme in the Warburg effect. Survival analysis indicated poor clinical outcomes in MIBC with high LDH-A expression. The results of in vitro experiment indicated that LDH-A promotes MIBC cells proliferation, invasion and migration. The positive relationship between LDH-A expression and CSC/EMT markers was confirmed both in invasive bladder cell line and in 136 MIBC specimens. Thus, we conclude that LDH-A may be a promising target for MIBC.

  18. Expression microarray meta-analysis identifies genes associated with Ras/MAPK and related pathways in progression of muscle-invasive bladder transition cell carcinoma.

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    Jonathan A Ewald

    Full Text Available The effective detection and management of muscle-invasive bladder Transition Cell Carcinoma (TCC continues to be an urgent clinical challenge. While some differences of gene expression and function in papillary (Ta, superficial (T1 and muscle-invasive (≥T2 bladder cancers have been investigated, the understanding of mechanisms involved in the progression of bladder tumors remains incomplete. Statistical methods of pathway-enrichment, cluster analysis and text-mining can extract and help interpret functional information about gene expression patterns in large sets of genomic data. The public availability of patient-derived expression microarray data allows open access and analysis of large amounts of clinical data. Using these resources, we investigated gene expression differences associated with tumor progression and muscle-invasive TCC. Gene expression was calculated relative to Ta tumors to assess progression-associated differences, revealing a network of genes related to Ras/MAPK and PI3K signaling pathways with increased expression. Further, we identified genes within this network that are similarly expressed in superficial Ta and T1 stages but altered in muscle-invasive T2 tumors, finding 7 genes (COL3A1, COL5A1, COL11A1, FN1, ErbB3, MAPK10 and CDC25C whose expression patterns in muscle-invasive tumors are consistent in 5 to 7 independent outside microarray studies. Further, we found increased expression of the fibrillar collagen proteins COL3A1 and COL5A1 in muscle-invasive tumor samples and metastatic T24 cells. Our results suggest that increased expression of genes involved in mitogenic signaling may support the progression of muscle-invasive bladder tumors that generally lack activating mutations in these pathways, while expression changes of fibrillar collagens, fibronectin and specific signaling proteins are associated with muscle-invasive disease. These results identify potential biomarkers and targets for TCC treatments, and

  19. Long-term Outcomes After Bladder-preserving Tri-modality Therapy for Patients with Muscle-invasive Bladder Cancer: An Updated Analysis of the Massachusetts General Hospital Experience.

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    Giacalone, Nicholas J; Shipley, William U; Clayman, Rebecca H; Niemierko, Andrzej; Drumm, Michael; Heney, Niall M; Michaelson, Marc D; Lee, Richard J; Saylor, Philip J; Wszolek, Matthew F; Feldman, Adam S; Dahl, Douglas M; Zietman, Anthony L; Efstathiou, Jason A

    2017-06-01

    Tri-modality therapy (TMT) is a recognized treatment strategy for selected patients with muscle-invasive bladder cancer (MIBC). Report long-term outcomes of patients with MIBC treated by TMT. Four hundred and seventy-five patients with cT2-T4a MIBC were enrolled on protocols or treated as per protocol at the Massachusetts General Hospital between 1986 and 2013. Patients underwent transurethral resection of bladder tumor followed by concurrent radiation and chemotherapy. Patients with less than a complete response (CR) to chemoradiation or with an invasive recurrence were recommended to undergo salvage radical cystectomy. Disease-specific survival (DSS) and overall survival (OS) were calculated using the Kaplan-Meier method. Median follow-up for surviving patients was 7.21 yr. Five- and 10-yr DSS rates were 66% and 59%, respectively. Five- and 10-yr OS rates were 57% and 39%, respectively. The risk of salvage cystectomy at 5 yr was 29%. In multivariate analyses, T2 disease (OS hazard ratio [HR]: 0.57, 95% confidence interval [CI]: 0.44-0.75, DSS HR: 0.51, 95% CI: 0.36-0.73), CR to chemoradiation (OS HR: 0.61, 95% CI: 0.46-0.81, DSS HR: 0.49, 95% CI: 0.34-0.71), and presence of tumor-associated carcinoma in situ (OS HR: 1.56, 95% CI: 1.17-2.08, DSS HR: 1.50, 95% CI: 1.03-2.17) were significant predictors for OS and DSS. When evaluating our cohort over treatment eras, rates of CR improved from 66% to 88% and 5-yr DSS improved from 60% to 84% during the eras of 1986-1995 to 2005-2013, while the 5-yr risk of salvage radical cystectomy rate decreased from 42% to 16%. These data demonstrate high rates of CR and bladder preservation in patients receiving TMT, and confirm DSS rates similar to modern cystectomy series. Contemporary results are particularly encouraging, and therefore TMT should be discussed and offered as a treatment option for selected patients. Tri-modality therapy is an alternative to radical cystectomy for patients with muscle-invasive bladder cancer, and

  20. Platinum Concentration and Pathologic Response to Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer.

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    Elizabeth A Guancial

    Full Text Available Platinum (Pt-based chemotherapy is the standard of care for muscle-invasive bladder cancer (MIBC. However, resistance is a major limitation. Reduced intratumoral drug accumulation is an important mechanism of platinum resistance. Our group previously demonstrated a significant correlation between tissue Pt concentration and tumor response to Pt-based neoadjuvant chemotherapy (NAC in lung cancer. We hypothesized that increased Pt concentration in radical cystectomy (RC specimens would correlate with improved pathologic response to Pt-based NAC in MIBC.A cohort of 19 clinically annotated, archived, fresh frozen RC specimens from patients with MIBC treated with Pt-based NAC was identified [ypT0 (pathologic complete response, pCR, N = 4; ≤ypT1N0M0 (pathologic partial response, pPR, N = 6; ≥ypT2 (minimal pathologic response/progression, N = 9]. RC specimens from 2 patients with MIBC who did not receive NAC and 1 treated with a non-Pt containing NAC regimen were used as negative controls. Total Pt concentration in normal adjacent urothelial tissue and bladder tumors from RC specimens was measured by flameless atomic absorption spectrophotometry.Total Pt concentration in normal urothelium differed by tumor pathologic response (P = 0.011. Specimens with pCR had the highest Pt concentrations compared to those with pPR (P = 0.0095 or no response/progression (P = 0.020. There was no significant difference in Pt levels in normal urothelium and tumor between pPR and no response/progression groups (P = 0.37; P = 0.25, respectively.Our finding of increased intracellular Pt in RC specimens with pCR following NAC for MIBC compared to those with residual disease suggests that enhanced Pt accumulation may be an important determinant of Pt sensitivity. Factors that modulate intracellular Pt concentration, such as expression of Pt transporters, warrant further investigation as predictive biomarkers of response to Pt-based NAC in MIBC.

  1. Current status of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer.

    Science.gov (United States)

    Rosenberg, Jonathan E

    2007-12-01

    Muscle-invasive transitional cell carcinoma occurs in approximately 30% of patients and is associated with a high risk of distant metastasis. Radical local therapy in the form of cystectomy or radiotherapy is curative in a portion of patients. Systemic therapy to treat occult micrometastasis at the time of local control is necessary to improve outcomes. Neoadjuvant chemotherapy is associated with a 5-6% improvement in overall survival at 5 years, and adjuvant chemotherapy may achieve similar results, although this remains unproven. Operative complications are not increased with neoadjuvant therapy. Perioperative treatment strategies remain underutilized, and many patients are not offered treatment to reduce the risk of relapse. Neoadjuvant strategies are a potent tool for research and should be employed to test new agents for the treatment of transitional cell carcinoma.

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

    Science.gov (United States)

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

    2014-03-01

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

  3. Expression of RFC/SLC19A1 is associated with tumor type in bladder cancer patients.

    Science.gov (United States)

    Abdel-Haleem, Alyaa M; El-Zeiry, Maha I; Mahran, Laila G; Abou-Aisha, Khaled; Rady, Mona H; Rohde, Jan; Mostageer, Marwa; Spahn-Langguth, Hilde

    2011-01-01

    Urinary bladder cancer (UBC) ranks ninth in worldwide cancer. In Egypt, the pattern of bladder cancer is unique in that both the transitional and squamous cell types prevail. Despite much research on the topic, it is still difficult to predict tumor progression, optimal therapy and clinical outcome. The reduced folate carrier (RFC/SLC19A1) is the major transport system for folates in mammalian cells and tissues. RFC is also the primary means of cellular uptake for antifolate cancer chemotherapeutic drugs, however, membrane transport of antifolates by RFC is considered as limiting to antitumor activity. The purpose of this study was to compare the mRNA expression level of RFC/SLC19A1 in urothelial and non-urothelial variants of bladder carcinomas. Quantification of RFC mRNA in the mucosa of 41 untreated bladder cancer patients was performed using RT-qPCR. RFC mRNA steady-state levels were ∼9-fold higher (N = 39; PRFC upregulation was strongly correlated with tumor type (urothelial vs. non-urothelial; pRFC mRNA expression was significantly (pRFC mRNA levels were not associated with tumor grade (I, II and III) or stage (muscle-invasive vs. non-muscle invasive) implying that RFC cannot be used for prognostic purposes in bladder carcinomas and its increased expression is an early event in human bladder tumors pathogenesis. Further, RFC can be considered as a potential marker for predicting response to antifolate chemotherapy in urothelial carcinomas.

  4. Non-invasive clinical parameters for the prediction of urodynamic bladder outlet obstruction: analysis using causal Bayesian networks.

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    Myong Kim

    Full Text Available To identify non-invasive clinical parameters to predict urodynamic bladder outlet obstruction (BOO in patients with benign prostatic hyperplasia (BPH using causal Bayesian networks (CBN.From October 2004 to August 2013, 1,381 eligible BPH patients with complete data were selected for analysis. The following clinical variables were considered: age, total prostate volume (TPV, transition zone volume (TZV, prostate specific antigen (PSA, maximum flow rate (Qmax, and post-void residual volume (PVR on uroflowmetry, and International Prostate Symptom Score (IPSS. Among these variables, the independent predictors of BOO were selected using the CBN model. The predictive performance of the CBN model using the selected variables was verified through a logistic regression (LR model with the same dataset.Mean age, TPV, and IPSS were 6.2 (±7.3, SD years, 48.5 (±25.9 ml, and 17.9 (±7.9, respectively. The mean BOO index was 35.1 (±25.2 and 477 patients (34.5% had urodynamic BOO (BOO index ≥40. By using the CBN model, we identified TPV, Qmax, and PVR as independent predictors of BOO. With these three variables, the BOO prediction accuracy was 73.5%. The LR model showed a similar accuracy (77.0%. However, the area under the receiver operating characteristic curve of the CBN model was statistically smaller than that of the LR model (0.772 vs. 0.798, p = 0.020.Our study demonstrated that TPV, Qmax, and PVR are independent predictors of urodynamic BOO.

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

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    Tilman Todenhöfer

    2014-01-01

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

  6. Re-examination of the Natural History of High-grade T1 Bladder Cancer using a Large Contemporary Cohort

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    Daniel J. Canter

    2014-04-01

    Full Text Available IntroductionHigh-grade T1 (HGT1 bladder cancer represents a clinical challenge in that the urologist must balance the risk of disease progression against the morbidity and potential mortality of early radical cystectomy and urinary diversion. Using two non-muscle invasive bladder cancer (NMIBC databases, we re-examined the rate of progression of HG T1 bladder cancer in our bladder cancer populations.Materials and MethodsWe queried the NMIBC databases that have been established independently at the Atlanta Veterans Affairs Medical Center (AVAMC and the University of Pennsylvania to identify patients initially diagnosed with HGT1 bladder cancer. Demographic, clinical, and pathologic variables were examined as well as rates of recurrence and progression.ResultsA total of 222 patients were identified; 198 (89.1% and 199 (89.6% of whom were male and non-African American, respectively. Mean patient age was 66.5 years. 191 (86.0% of the patients presented with isolated HG T1 disease while 31 (14.0% patients presented with HGT1 disease and CIS. Induction BCG was utilized in 175 (78.8% patients. Recurrence occurred in 112 (50.5% patients with progression occurring in only 19 (8.6% patients. At a mean follow-up of 51 months, overall survival was 76.6%. Fifty two patients died, of whom only 13 (25% patient deaths were bladder cancer related.ConclusionsIn our large cohort of patients, we found that the risk of progression at approximately four years was only 8.6%. While limited by its retrospective nature, this study could potentially serve as a starting point in re-examining the treatment algorithm for patients with HG T1 bladder cancer.

  7. International Consultation on Incontinence-Research Society (ICI-RS) Report on Non-Invasive Urodynamics: The Need of Standardization of Ultrasound Bladder and Detrusor Wall Thickness Measurements to Quantify Bladder Wall Hypertrophy

    NARCIS (Netherlands)

    M. Oelke

    2010-01-01

    Introduction: Ultrasonic measurements of urinary bladders are suitable to quantify bladder wall hypertrophy due to bladder outlet obstruction, detrusor overactivity, or neurogenic bladder dysfunction in adult men or women and in children. Quantification of bladder wall hypertrophy seems to be useful

  8. Silencing Trim59 inhibits invasion/migration and epithelial-to-mesenchymal transition via TGF-β/Smad2/3 signaling pathway in bladder cancer cells

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    Chen W

    2017-03-01

    Full Text Available Wei Chen,1,* Kai Zhao,2,* Chenkui Miao,2,* Aiming Xu,2 Jianzhong Zhang,2 Jundong Zhu,2 Shifeng Su,2 Zengjun Wang2 1Department of Urology, Nanjing First Hospital, Nanjing Medical University, 2State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: The evolutionarily conserved genes that encode the tripartite motif (TRIM protein family are involved in various biological processes, including cellular immunity, inflammatory reaction, antiviral activity, and tumor progression. One member of this protein family, Trim59, has been reported as a novel biomarker for the occurrence and progression of multiple human carcinomas, such as lung cancer, gastric cancer, cervical cancer, and osteosarcoma. However, little is known about the relationship between Trim59 and bladder carcinogenesis. In this study, we examined the expression of Trim59 in bladder cancer (Bca specimens and cell lines, and investigated its biological roles in Bca cell lines. We found that Trim59 was upregulated in Bca tissues and cell lines. In addition, using transwell chamber assays and the cell scratch test, we determined that knockdown of Trim59 significantly inhibited the epithelial-mesenchymal transition (EMT and the processes of cell invasion and migration in Bca cell lines. Furthermore, we found that downregulated Trim59 expression could also inhibit cell proliferation and promote apoptosis. As a result, we demonstrated that the effects of Trim59-induced EMT and invasion/migration in Bca cells were achieved by the activation of the transforming growth factor beta/Smad2/3 signaling pathway. Our findings also revealed that Trim59 can present oncogenic activity, and may serve as a novel candidate target for bladder carcinoma treatment. Keywords: Trim59, bladder carcinoma, EMT, metastasis, TGF-β, Smad2/3

  9. Impact of lymphovascular invasion on recurrence and progression rates in patients with pT1 urothelial carcinoma of bladder after transurethral resection

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    Sha N

    2015-11-01

    Full Text Available Nan Sha,* Linguo Xie,* Tao Chen,* Chen Xing, Xiaoteng Liu, Yu Zhang, Zhonghua Shen, Hao Xu, Zhouliang Wu, Hailong Hu, Changli Wu Department of Urology, Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China *These authors contributed equally to this work Objective: To evaluate the clinical significance of lymphovascular invasion (LVI on recurrence and progression rates in patients with pT1 urothelial carcinoma of bladder after transurethral resection.Methods: This retrospective study was performed with 155 patients with newly diagnosed pT1 urothelial carcinoma of bladder who were treated with transurethral resection of bladder tumor at our institution from January 2006 to January 2010. The presence or absence of LVI was examined by pathologists. Chi-square test was performed to identify the correlations between LVI and other clinical and pathological features. Kaplan–Meier method was used to estimate the recurrence-free survival (RFS and progression-free survival curves and difference was determined by the log-rank test. Univariate and multivariate analyses were performed to determine the predictive factors through a Cox proportional hazards analysis model.Results: LVI was detected in a total of 34 patients (21.9%. While LVI was associated with high-grade tumors (P<0.001 and intravesical therapy (P=0.009. Correlations with age (P=0.227, sex (P=0.376, tumor size (P=0.969, tumor multiplicity (P=0.196, carcinoma in situ (P=0.321, and smoking (P=0.438 were not statistically significant. There was a statistically significant tendency toward higher recurrence rate and shorter RFS time in LVI-positive patients. However, no statistically significant differences were observed in progression rate between the two groups. Moreover, multivariate Cox proportional hazards analysis revealed that LVI, tumor size, and smoking were independent prognostic predictors of

  10. Suppressions of Migration and Invasion by Cantharidin in TSGH-8301 Human Bladder Carcinoma Cells through the Inhibitions of Matrix Metalloproteinase-2/-9 Signaling

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    Yi-Ping Huang

    2013-01-01

    Full Text Available Cancer metastasis becomes an initial cause of cancer death in human population. In many cancers, it has been shown that the high levels of matrix metalloproteinase (MMP-2 and/or MMP-9 are associated with the invasive phenotypes of cancer cells. In this study, we investigated the effects of cantharidin, a derivative of blister beetles which is one of the traditional Chinese medicines, on the adhesion, migration, and invasion of human bladder cancer TSGH-8301 cells. Cantharidin effectively suppressed TSGH-8301 cell adhesion, migration, and invasion in a concentration-dependent manner. Results from Western blotting, RT-PCR, and gelatin zymography assays indicated that cantharidin blocked the protein levels, gene expression (mRNA, and activities of MMP-2 and -9 in TSGH-8301 cells. Cantharidin also significantly suppressed the protein expressions of p-p38 and p-JNK1/2 in TSGH-8301 cells. Taken together, cantharidin was suggested to present antimetastatic potential via suppressing the levels of MMP-2 and MMP-9 expression that might be mediated by targeting the p38 and JNK1/2 MAPKs pathway in TSGH-8301 human bladder cancer cells.

  11. Effect of Raykeen holmium laser electric resection and conventional electric resection on malignant degree and immune function of non-invasive bladder cancer

    Institute of Scientific and Technical Information of China (English)

    Liang-Suo Zhang

    2016-01-01

    Objective:To analyze the effect of Raykeen holmium laser electric resection and conventional electric resection on the malignant degree and immune function of non-invasive bladder cancer. Methods:A total of 96 cases of patients with non-invasive bladder cancer were included for study and divided into observation group 46 cases who received Raykeen holmium laser electric resection treatment and control group 50 cases who received conventional electric resection treatment. Differences in postoperative illness-related indexes, serum adhesion molecule levels, urinary sediment miRNA and immune function-related indexes were compared between two groups.Results:Serum DKK-3 and Endostatin values of observation group after treatment were higher than those of control group while CIP2A, DKK-1 and sFasL values were lower than those of control group; serum CD44v6, E-cadherin and hepaCAM values of observation group after treatment were higher than those of control group while EpCAM, sVCAM-1 and sICAM-1 values were lower than those of control group; urinary sediment miR-129, miR-125b, miR-720, miR-191 and miR-107 expression levels of observation group after treatment were lower than those of control group; serum IgG, IgA, IgM, C3, C4, CD4+ and CD4+/CD8+ values of observation group after treatment were higher than those of control group while CD8+ value was lower than that of control group.Conclusions:Raykeen holmium laser electric resection treatment of patients with non-invasive bladder cancer can effectively reduce the malignant degree of tumor and improve body’s immune function, and it has positive clinical significance.

  12. Is [F-18]-fluorodeoxyglucose FDG-PET/CT better than CT alone for the preoperative lymph node staging of muscle invasive bladder cancer?

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    Uttam, Mete; Pravin, Nayak; Anish, Bhattacharya; Nandita, Kakkar; Arup, Mandal, E-mail: uttam_mete@yahoo.com [PGIMER, Chandigarh, (India)

    2016-03-15

    Objective: To evaluate whether the use of [F-18]-FDG-PET/CT can accurately predict pelvic lymph node metastasis in patients with muscle invasive TCC of the bladder undergoing radical cystectomy. Materials and methods: Fifteen patients with muscle invasive bladder cancer had undergone FDG-PET/CT scan from the skull base to the mid-thighs after IV injection of 6.5MBq (Mega-Becquerel)/Kg of FDG. After intravenous hydration IV furosemide was given to overcome the difficulties posed by urinary excretion of {sup 18}F-FDG. PET/ CT data were analyzed as PET and CT images studied separately as well as fused PET/ CT images. The imaging findings were correlated with the histopathology of the nodes (gold standard). Results: CT and FDG-PET had demonstrated positive lymph nodes in 9 & 8 patients respectively. Among the 15 patients 3 had documented metastasis on histopathology. Both CT and PET could detect the nodes in all these 3 patients (100% sensitivity). Nodes were histologically negative amongst 6&5 patients who had node involvement by CT and PET respectively. Therefore, specificity, positive predictive value (PPV) & negative predictive value (NPV) for CT and PET/CT were 50%, 33.3%, 100% and 58.3%, 37.5%, 100% respectively. Conclusion: The theoretical advantage of this cutting edge technology for whole body imaging has not been translated into clinical practice as we found minimal advantage of combined FDG-PET/CT over CT alone for nodal staging of muscle invasive bladder cancer. This may be due to substantial overlap between standardized uptake values (SUVs) from active inflammatory processes with those of malignant lesion. (author)

  13. Clinical utility of three-dimensional contrast-enhanced ultrasound in the differentiation between noninvasive and invasive neoplasms of urinary bladder

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qiu-yang, E-mail: qiuyang0925@gmail.com [Department of Ultrasound, Chinese People' s Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853 (China); Tang, Jie, E-mail: txiner@vip.sina.com [Department of Ultrasound, Chinese People' s Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853 (China); He, En-hui, E-mail: nkvhg@163.com [Department of Ultrasound, Chinese People' s Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853 (China); Li, Yan-mi, E-mail: liyanmimen@yahoo.com.cn [Department of Ultrasound, Chinese People' s Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853 (China); Zhou, Yun, E-mail: zhouyun_369@163.com [Department of Ultrasound, Chinese People' s Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853 (China); Zhang, Xu, E-mail: xzhang@tjh.tjmu.edu.cn [Department of Urology, Chinese People' s Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853 (China); Chen, Guangfu, E-mail: chen_gf@yanhoo.com [Department of Urology, Chinese People' s Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853 (China)

    2012-11-15

    Objectives: The purpose of this study was to evaluate the effectiveness of three-dimensional contrast-enhanced ultrasound in differentiating invasive and noninvasive neoplasms of urinary bladder. Methods: A total of 60 lesions in 60 consecutive patients with bladder tumors received three dimensional ultrasonography, low acoustic power contrast enhanced ultrasonography and low acoustic power three-dimensional contrast-enhanced ultrasound examination. The IU22 ultrasound scanner and a volume transducer were used and the ultrasound contrast agent was SonoVue. The contrast-specific sonographic imaging modes were PI (pulse inversion) and PM (power modulation). The three dimensional ultrasonography, contrast enhanced ultrasonography, and three-dimensional contrast-enhanced ultrasound images were independently reviewed by two readers who were not in the images acquisition. Images were analyzed off-site. A level of confidence in the diagnosis of tumor invasion of the muscle layer was assigned on a 5 Degree-Sign scale. Receiver operating characteristic analysis was used to assess overall confidence in the diagnosis of muscle invasion by tumor. Kappa values were used to assess inter-readers agreement. Histologic diagnosis was obtained for all patients. Results: Final pathologic staging revealed 44 noninvasive tumors and 16 invasive tumors. Three-dimensional contrast-enhanced ultrasound depicted all 16 muscle-invasive tumors. The diagnostic performance of three-dimensional contrast-enhanced ultrasound was better than those of three dimensional ultrasonography and contrast enhanced ultrasonography. The receiver operating characteristic curves were 0.976 and 0.967 for three-dimensional contrast-enhanced ultrasound, those for three dimensional ultrasonography were 0.881 and 0.869, those for contrast enhanced ultrasonography were 0.927 and 0.929. The kappa values in the three dimensional ultrasonography, contrast enhanced ultrasonography and three-dimensional contrast

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-22

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

  15. The efficacy of hemostatic radiotherapy for bladder cancer-related hematuria in patients unfit for surgery

    Directory of Open Access Journals (Sweden)

    E. Lacarriere

    2013-12-01

    Full Text Available Objective The aim of our study was to assess short and mid-term clinical efficacy of external beam radiation therapy to achieve hemostasis in patients with bladder-cancer related gross hematuria who were unfit for surgery. We also assessed hypofractionation as a possible alternative option for more severe patients. Patients and Methods Thirty-two patients were included for hemostatic radiation therapy, with two schedules based on Eastern Cooperative Oncology Group performance status. The standard treatment was 30 Gy in 10 fractions over 2 weeks. More severe patients underwent a hypofractionated regimen, with 20 Gy in 5 fractions over a one week period. Clinical evaluation was performed at 2 weeks and 6 months. Results At 2 weeks, 69% of patients were hematuria-free. Subgroup analysis showed that 79% of patients undergoing hypofractionated regimen were hematuria-free. A total of 54% were hematuria-free with the standard regimen. Based on tumor stage, hematuria was controlled at 2 weeks for 57% of non-muscle invasive tumors and 72% of muscle-invasive tumors. After 6 months, 69% of patients had relapsed, regardless of tumor stage or therapy schedules. Conclusions Hemostatic radiotherapy is an effective option for palliative-care hematuria related to bladder cancer in patients unfit for surgery. Although it appears to be rapidly effective, its effect is of limited duration. Hypofractionation also seems to be an effective option; however larger cohorts and prospective trials are needed to evaluate its efficacy compared to standard schedules.

  16. Biomatrices for bladder reconstruction.

    Science.gov (United States)

    Lin, Hsueh-Kung; Madihally, Sundar V; Palmer, Blake; Frimberger, Dominic; Fung, Kar-Ming; Kropp, Bradley P

    2015-03-01

    There is a demand for tissue engineering of the bladder needed by patients who experience a neurogenic bladder or idiopathic detrusor overactivity. To avoid complications from augmentation cystoplasty, the field of tissue engineering seeks optimal scaffolds for bladder reconstruction. Naturally derived biomaterials as well as synthetic and natural polymers have been explored as bladder substitutes. To improve regenerative properties, these biomaterials have been conjugated with functional molecules, combined with nanotechology, or seeded with exogenous cells. Although most studies reported complete and functional bladder regeneration in small-animal models, results from large-animal models and human clinical trials varied. For functional bladder regeneration, procedures for biomaterial fabrication, incorporation of biologically active agents, introduction of nanotechnology, and application of stem-cell technology need to be standardized. Advanced molecular and medical technologies such as next generation sequencing and magnetic resonance imaging can be introduced for mechanistic understanding and non-invasive monitoring of regeneration processes, respectively.

  17. ErbB2 and NFκB overexpression as predictors of chemoradiation resistance and putative targets to overcome resistance in muscle-invasive bladder cancer.

    Directory of Open Access Journals (Sweden)

    Fumitaka Koga

    Full Text Available Radical cystectomy for muscle-invasive bladder cancer (MIBC patients frequently impairs their quality of life (QOL due to urinary diversion. To improve their QOL, a bladder-sparing alternative strategy using chemoradiation has been developed. In bladder-sparing protocols, complete response (CR to induction chemoradiation is a prerequisite for bladder preservation and favorable survival. Thus predicting chemoradiation resistance and overcoming it would increase individual MIBC patients' chances of bladder preservation. The aim of this study is to investigate putative molecular targets for treatment aimed at improving chemoradiation response. Expression levels of erbB2, NFκB, p53, and survivin were evaluated immunohistochemically in pretreatment biopsy samples from 35 MIBC patients in whom chemoradiation sensitivity had been pathologically evaluated in cystectomy specimens, and associations of these expression levels with chemoradiation sensitivity and cancer-specific survival (CSS were investigated. Of the 35 patients, 11 (31% achieved pathological CR, while tumors in the remaining 24 patients (69% were chemoradiation-resistant. Multivariate analysis identified erbB2 and NFκB overexpression and hydronephrosis as significant and independent risk factors for chemoradiation resistance with respective relative risks of 11.8 (P = 0.014, 15.4 (P = 0.024 and 14.3 (P = 0.038. The chemoradiation resistance rate was 88.5% for tumors overexpressing erbB2 and/or NFκB, but only 11.1% for those negative for both (P <0.0001. The 5-year CSS rate was 74% overall. Through multivariate analysis, overexpression of erbB2 and/or NFκB was identified as an independent risk factor for bladder cancer death with marginal significance (hazard ratio 21.5, P = 0.056 along with chemoradiation resistance (P = 0.003 and hydronephrosis (P = 0.018. The 5-year CSS rate for the 11 patients achieving pathological CR was 100%, while that for the 24 with

  18. Impact of age and gender on the clinicopathological characteristics of bladder cancer

    Directory of Open Access Journals (Sweden)

    Parag Gupta

    2009-01-01

    Full Text Available Purpose: To determine the impact of age and gender on the clinicopathological characteristics of histologically confirmed bladder cancer in India. Materials and Methods: From January 2001 to June 2008, records of patients with bladder cancer were evaluated for age and gender at presentation, clinical symptoms, cystoscopic finding, history of smoking, and histopathological characteristics. A total of 561 patients were identified from the computer-based hospital information system and the case files of patients. Results: A total of 97% of the patients presented with painless hematuria. The mean age was 60.2 ± 4.4 years old (range: 18-90 years old and the male to female ratio was 8.6:1. Transitional cell carcinoma (TCC was the most common histological variety, which was present in 97.71% (470 of 481 of the patients. A total of 26% of the patients had muscle invasive disease at the time of presentation. However, 34.5% (166 of 481 of the patients did not show any evidence of detrusor muscle in their biopsy specimen. In patients with nonmuscle-invasive bladder carcinoma, 55% had p Ta while 45% had p T1. Overall, 44.7% (215 of 481 of the patients had low-grade disease. Among patients younger than 60 years old, low-grade (51.0% vs. 38.1%; P = 0.006 and low-stage (77.1% vs. 70.8%; P = 0.119 disease were more prevalent than in patients older than 60 years old. The incidence of smoking was much higher among males compared with females (74% vs. 22%. Conclusion: TCC is the predominant cancer, with significant male preponderance among Indian patients. Younger-aged patients have low-grade disease. Hematuria is the most common presentation and greater awareness is needed not to overlook bladder cancer.

  19. LDH-A promotes malignant progression via activation of epithelial-to-mesenchymal transition and conferring stemness in muscle-invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Fujin [Department of Urinary Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu (China); Department of Urinary Surgery, Huai' an Hospital to Xuzhou Medical University, Huai' an, Jiangsu (China); Ma, Song [Department of Urinary Surgery, Huai' an Hospital to Xuzhou Medical University, Huai' an, Jiangsu (China); Xue, Yubao [Department of Medical Oncology, Huai' an Hospital to Xuzhou Medical University, Huai' an, Jiangsu (China); Hou, Jianquan, E-mail: Jianquanhou@aliyun.com [Department of Urinary Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu (China); Zhang, Yongjie, E-mail: zhangyj0818@126.com [Department of Medical Oncology, Huai' an Hospital to Xuzhou Medical University, Huai' an, Jiangsu (China)

    2016-01-22

    Lactate dehydrogenase-A(LDH-A) is an important rate-limiting enzyme in the Warburg effect. Survival analysis indicated poor clinical outcomes in MIBC with high LDH-A expression. The results of in vitro experiment indicated that LDH-A promotes MIBC cells proliferation, invasion and migration. The positive relationship between LDH-A expression and CSC/EMT markers was confirmed both in invasive bladder cell line and in 136 MIBC specimens. Thus, we conclude that LDH-A may be a promising target for MIBC. - Highlights: • Survival analysis indicated poor clinical outcomes in MIBC with high LDH-A expression. • IHC analysis of 136 MIBC specimens revealed increased LDH-A is correlated with positive Oct4 and negative E-cadherin. • In vitro experiments demonstrated LDH-A promotes MIBC progression by positive regulation of EMT/CSC.

  20. Trends in the Use of Chemotherapy before and after Radical Cystectomy in Patients with Muscle-invasive Bladder Cancer in Korea.

    Science.gov (United States)

    Kim, Sung Han; Seo, Ho Kyung; Shin, Hee Chul; Chang, Sung Ja; Yun, Sooin; Joo, Jungnam; Ku, Ja Hyeon; Kim, Hyung Suk; Jeon, Hwang Gyun; Jeong, Byong Chang; Jeong, In Gab; Kang, Seok Ho; Hong, Bumsik

    2015-08-01

    We investigated trends in perioperative chemotherapy use, and determined factors associated with neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) use in Korean patients with muscle-invasive bladder cancer (MIBC). We recruited 1,324 patients who had MIBC without nodal invasion or metastases and had undergone radical cystectomies (RC) between 2003 and 2013. The study's cut-off time for AC was three months after surgery, and the study's timespan was divided into three periods based on NAC use, namely, 2003-2005, 2006-2009, and 2010-2013. Complete remission was defined as histologically confirmed T0N0M0 after RC. NAC and AC were administered to 7.3% and 18.1% of the patients, respectively. The median time interval between completing NAC and undergoing RC was 32 days and the mean number of cycles was 3.2. The median time interval between RC and AC was 43 days and the mean number of cycles was 4.1. Gemcitabine and cisplatin were most frequently used in combination for NAC (49.0%) and AC (74.9%). NAC use increased significantly from 4.6% between 2003 and 2005 to 8.4% between 2010 and 2013 (P tumor stage ≤ cT2 bladder cancer were negatively associated with NAC use (P < 0.05). While NAC use has slowly increased over time, it remains an underutilized therapeutic approach in Korean clinical practice.

  1. Kinetic profiles by topographic compartments in muscle-invasive transitional cell carcinomas of the bladder: role of TP53 and NF1 genes.

    Science.gov (United States)

    Blanes, Alfredo; Rubio, Javier; Martinez, Armando; Wolfe, Hubert J; Diaz-Cano, Salvador J

    2002-07-01

    We evaluated 71 muscle-invasive transitional cell carcinomas (TCCs) of the bladder by tumor compartments. Kinetic parameters included mitotic figure counting, Ki-67 index, proliferation rate (DNA slide cytometry), and apoptotic index (in situ end labeling [ISEL] of fragmented DNA using digoxigenin-labeled deoxyuridine triphosphate and Escherichia coli DNA polymerase [Klenow fragment]). At least 50 high-power fields per compartment were screened from the same tumor areas; results are expressed as percentage of positive neoplastic cells. Mean and SD were compared by tumor compartment. DNA was extracted from microdissected samples (superficial and deep) and used for microsatellite analysis of TP53 and NF1 by polymerase chain reaction-denaturing gradient gel electrophoresis. Significantly higher marker scores were revealed in the superficial compartment than in the deep compartment. An ISEL index of less than 1% was revealed in 63% (45/71) of superficial compartments and 86% (61/71) of deep compartments. Isolated NF1 alterations were observed mainly in superficial compartments, whereas isolated TP53 abnormalities were present in deep compartments. Lower proliferation and down-regulation of apoptosis define kinetically the deep compartment of muscle-invasive TCC of the bladder and correlate with the topographic heterogeneity, NF1-defective in superficial compartments and TP53-defective in deep compartments.

  2. Therapeutic effect evaluation of TUPKEP combined with percutaneous cystotomy and nephroscopic EMS minimally invasive therapy for benign prostatic hyperplasia with multiple large bladder calculi

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hu Zhu; Bing-Xun He; Hou-Bin Kang

    2016-01-01

    Objective:To study the therapeutic effect of TUPKEP combined with nephroscopic EMS pneumatic minimally invasive therapy for benign prostatic hyperplasia with multiple large bladder calculi.Methods: Benign prostatic hyperplasia patients with multiple (large) bladder calculi who received surgical treatment in our hospital from May 2012 to October 2015 were selected as the research subjects and randomly divided into TUPKEP group and TURP group, and then perioperative situation, serum PSA levels, liver and kidney function and the degree of inflammation were compared between two groups.Results: During operation, the amount of bleeding and the weight of removed prostate of TUPKEP group were significantly lower than those of TURP group; during postoperative recovery, the time of retention catheterization of TUPKEP group was shorter than that of TURP group; 1 d, 3 d and 7 d after operation, serum PSA levels of both groups were significantly higher than those before operation and serum PSA levels of TUPKEP group were significantly lower than those of TURP group; 3 days after operation, ALT, AST, BUN and Scr levels of TUPKEP group and TURP group were not different, and IL-1β and IL-18 levels in serum as well as mRNA levels of NLPR3, ACS, Caspase-1, IL-1β and IL-18 in peripheral blood mononuclear cells of TUPKEP group were significantly lower than those of TURP group.Conclusion: TUPKEP combined with nephroscopic EMS pneumatic minimally invasive therapy for benign prostatic hyperplasia with multiple large bladder calculi causes less damage, has better resection effect on the hyperplastic gland tissue than TURP, and has equivalent long-term curative effect to TURP.

  3. UroVysion compared with cytology and quantitative cytology in the surveillance of non-muscle-invasive bladder cancer.

    NARCIS (Netherlands)

    Moonen, P.M.J.; Merkx, G.F.M.; Peelen, P.; Karthaus, H.F.M.; Smeets, D.F.C.M.; Witjes, J.A.

    2007-01-01

    OBJECTIVES: The multitarget fluorescence in situ hybridization probe set Vysis UroVysion, consisting of probes for chromosomes 3, 7, and 17 and for the 9p21 band, was studied to evaluate its value in the follow-up of patients with bladder cancer. The results were compared with conventional cytology

  4. Defect in lectin-induced interleukin 2 production by peripheral blood lymphocytes of patients with invasive urinary bladder carcinoma

    DEFF Research Database (Denmark)

    Bubeník, J; Kieler, J; Tromholt, V

    1988-01-01

    The production of interleukin 2 (IL-2) by phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) from 21 patients with transitional cell carcinoma of the urinary bladder (BTCC) and 16 control blood donors was measured with a solid phase enzyme immunoassay based on the dual...

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

    Science.gov (United States)

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

    2007-09-15

    We studied if bladder cancers respond to HAMLET (human alpha-lactalbumin made lethal to tumor cells) to establish if intravesical HAMLET application might be used to selectively remove cancer cells in vivo. Patients with nonmuscle invasive transitional cell carcinomas were included. Nine patients received 5 daily intravesical instillations of HAMLET (25 mg/ml) during the week before scheduled surgery. HAMLET stimulated a rapid increase in the shedding of tumor cells into the urine, daily, during the 5 days of instillation. The effect was specific for HAMLET, as intravesical instillation of NaCl, PBS or native alpha-lactalbumin did not increase cell shedding. Most of the shed cells were dead and an apoptotic response was detected in 6 of 9 patients, using the TUNEL assay. At surgery, morphological changes in the exophytic tumors were documented by endoscopic photography and a reduction in tumor size or change in tumor character was detected in 8 of 9 patients. TUNEL staining was positive in biopsies from the remaining tumor in 4 patients but adjacent healthy tissue showed no evidence of apoptosis and no toxic response. The results suggest that HAMLET exerts a direct and selective effect on bladder cancer tissue in vivo and that local HAMLET administration might be of value in the future treatment of bladder cancers. (c) 2007 Wiley-Liss, Inc.

  6. Current clinical practice gaps in the treatment of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) with emphasis on the use of bacillus Calmette-Guerin (BCG): results of an international individual patient data survey (IPDS)

    NARCIS (Netherlands)

    Witjes, J.A.; Palou, J.; Soloway, M.; Lamm, D.; Kamat, A.M.; Brausi, M.; Persad, R.; Buckley, R.; Colombel, M.; Bohle, A.

    2013-01-01

    OBJECTIVES: To examine the management of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), particularly with regard to the use of bacillus Calmette-Guerin (BCG) therapy, in North America and Europe. To compare NMIBC management practices to European Association of Urology (EAU)

  7. Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs

    Directory of Open Access Journals (Sweden)

    Christopher M. Fulkerson

    2017-01-01

    Full Text Available Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

  8. Artificial intelligence for predicting recurrence-free probability of non-invasive high-grade urothelial bladder cell carcinoma.

    Science.gov (United States)

    Cai, Tommaso; Conti, Gloria; Nesi, Gabriella; Lorenzini, Matteo; Mondaini, Nicola; Bartoletti, Riccardo

    2007-10-01

    The objective of our study was to define a neural network for predicting recurrence and progression-free probability in patients affected by recurrent pTaG3 urothelial bladder cancer to use in everyday clinical practice. Among all patients who had undergone transurethral resection for bladder tumors, 143 were finally selected and enrolled. Four follow-ups for recurrence, progression or survival were performed at 6, 9, 12 and 108 months. The data were analyzed by using the commercially available software program NeuralWorks Predict. These data were compared with univariate and multivariate analysis results. The use of Artificial Neural Networks (ANN) in recurrent pTaG3 patients showed a sensitivity of 81.67% and specificity of 95.87% in predicting recurrence-free status after transurethral resection of bladder tumor at 12 months follow-up. Statistical and ANN analyses allowed selection of the number of lesions (multiple, HR=3.31, p=0.008) and the previous recurrence rate (>or=2/year, HR=3.14, p=0.003) as the most influential variables affecting the output decision in predicting the natural history of recurrent pTaG3 urothelial bladder cancer. ANN applications also included selection of the previous adjuvant therapy. We demonstrated the feasibility and reliability of ANN applications in everyday clinical practice, reporting a good recurrence predicting performance. The study identified a single subgroup of pTaG3 patients with multiple lesions, >or=2/year recurrence rate and without any response to previous Bacille Calmette-Guérin adjuvant therapy, that seem to be at high risk of recurrence.

  9. Bladder Management

    Science.gov (United States)

    ... Catheterization • Urinary Tract Infections: Indwelling (Foley) Catheter Bladder Management [ Download this pamphlet: "Bladder Management" - (PDF, 499KB) ] The ... and medication or surgery may be helpful. Bladder Management Foley or Suprapubic Catheter A tube is inserted ...

  10. Bladder biopsy

    Science.gov (United States)

    Biopsy - bladder ... A bladder biopsy can be done as part of a cystoscopy . Cystoscopy is a telescopic examination of the inside of the ... informed consent form before you have a bladder biopsy. In most cases, you are asked to urinate ...

  11. ARID1A alterations are associated with FGFR3-wild type, poor-prognosis, urothelial bladder tumors.

    Directory of Open Access Journals (Sweden)

    Cristina Balbás-Martínez

    Full Text Available Urothelial bladder cancer (UBC is heterogeneous at the clinical, pathological, genetic, and epigenetic levels. Exome sequencing has identified ARID1A as a novel tumor suppressor gene coding for a chromatin remodeling protein that is mutated in UBC. Here, we assess ARID1A alterations in two series of patients with UBC. In the first tumor series, we analyze exons 2-20 in 52 primary UBC and find that all mutant tumors belong to the aggressive UBC phenotype (high grade non-muscle invasive and muscle invasive tumors (P = 0.05. In a second series (n = 84, we assess ARID1A expression using immunohistochemistry, a surrogate for mutation analysis, and find that loss of expression increases with higher stage/grade, it is inversely associated with FGFR3 overexpression (P = 0.03 but it is not correlated with p53 overexpression (P = 0.30. We also analyzed the expression of cytokeratins in the same set of tumor and find, using unsupervised clustering, that tumors with ARID1A loss of expression are generally KRT5/6-low. In this patient series, loss of ARID1A expression is also associated with worse prognosis, likely reflecting the higher prevalence of losses found in tumors of higher stage and grade. The independent findings in these two sets of patients strongly support the notion that ARID1A inactivation is a key player in bladder carcinogenesis occurring predominantly in FGFR3 wild type tumors.

  12. Assessment of the Radiation-Equivalent of Chemotherapy Contributions in 1-Phase Radio-chemotherapy Treatment of Muscle-Invasive Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Plataniotis, George A., E-mail: george.plataniotis@nhs.net [Department of Oncology, Queens Hospital, London (United Kingdom); Dale, Roger G. [Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London (United Kingdom)

    2014-03-15

    Purpose: To estimate the radiation equivalent of the chemotherapy contribution to observed complete response rates in published results of 1-phase radio-chemotherapy of muscle-invasive bladder cancer. Methods and Materials: A standard logistic dose–response curve was fitted to data from radiation therapy-alone trials and then used as the platform from which to quantify the chemotherapy contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of chemotherapy effect were assumed (1) a fixed radiation-independent contribution to local control; or (2) a fixed degree of chemotherapy-induced radiosensitization. A combination of both mechanisms was also considered. Results: The respective best-fit values of the independent chemotherapy-induced complete response (CCR) and radiosensitization (s) coefficients were 0.40 (95% confidence interval −0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70). Independent chemotherapy effect was slightly favored by the analysis, and the derived CCR value was consistent with reports of pathologic complete response rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive bladder cancer. The radiation equivalent of the CCR was 36.3 Gy. Conclusion: Although the data points in the analyzed radio-chemotherapy studies are widely dispersed (largely on account of the diverse range of chemotherapy schedules used), it is nonetheless possible to fit plausible-looking response curves. The methodology used here is based on a standard technique for analyzing dose-response in radiation therapy-alone studies and is capable of application to other mixed-modality treatment combinations involving radiation therapy.

  13. BCG-mediated bladder cancer immunotherapy: identifying determinants of treatment response using a calibrated mathematical model.

    Science.gov (United States)

    Rentsch, Cyrill A; Biot, Claire; Gsponer, Joël R; Bachmann, Alexander; Albert, Matthew L; Breban, Romulus

    2013-01-01

    Intravesical Bacillus Calmette Guérin (BCG) immunotherapy is considered the standard of care for treatment of non-muscle invasive bladder cancer; however the treatment parameters were established empirically. In order to evaluate potential optimization of clinical parameters of BCG induction therapy, we constructed and queried a new mathematical model. Specifically, we assessed the impact of (1) duration between resection and the first instillation; (2) BCG dose; (3) indwelling time; and (4) treatment interval of induction therapy - using cure rate as the primary endpoint. Based on available clinical and in vitro experimental data, we constructed and parameterized a stochastic mathematical model describing the interactions between BCG, the immune system, the bladder mucosa and tumor cells. The primary endpoint of the model was the probability of tumor extinction following BCG induction therapy in patients with high risk for tumor recurrence. We theoretically demonstrate that extending the duration between the resection and the first BCG instillation negatively influences treatment outcome. Simulations of higher BCG doses and longer indwelling times both improved the probability of tumor extinction. A remarkable finding was that an inter-instillation interval two times longer than the seven-day interval used in the current standard of care would substantially improve treatment outcome. We provide insight into relevant clinical questions using a novel mathematical model of BCG immunotherapy. Our model predicts an altered regimen that may decrease side effects of treatment while improving response to therapy.

  14. Bladder Diseases

    Science.gov (United States)

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

  15. Neurogenic bladder

    Science.gov (United States)

    Neurogenic detrusor overactivity; NDO; Neurogenic bladder sphincter dysfunction; NBSD ... Disorders of the central nervous system commonly cause neurogenic bladder. These can include: Alzheimer disease Birth defects of ...

  16. Randomized Noninferiority Trial of Reduced High-Dose Volume Versus Standard Volume Radiation Therapy for Muscle-Invasive Bladder Cancer: Results of the BC2001 Trial (CRUK/01/004)

    Energy Technology Data Exchange (ETDEWEB)

    Huddart, Robert A., E-mail: robert.huddart@icr.ac.uk [Institute of Cancer Research, Royal Marsden NHSFT (National Health Service Foundation Trust) (United Kingdom); Hall, Emma [Institute of Cancer Research (United Kingdom); Hussain, Syed A. [University of Liverpool (United Kingdom); Jenkins, Peter [Gloucestershire Hospitals NHSFT (United Kingdom); Rawlings, Christine [South Devon Healthcare NHSFT (United Kingdom); Tremlett, Jean [Brighton and Sussex University Hospitals (United Kingdom); Crundwell, Malcolm [Royal Devon and Exeter NHSFT (United Kingdom); Adab, Fawzi A. [University Hospital of North Staffordshire NHS Trust (United Kingdom); Sheehan, Denise [Royal Devon and Exeter NHSFT (United Kingdom); Syndikus, Isabel [Clatterbridge Cancer Centre NHSFT (United Kingdom); Hendron, Carey [University of Birmingham (United Kingdom); Lewis, Rebecca; Waters, Rachel [Institute of Cancer Research (United Kingdom); James, Nicholas D. [University of Birmingham (United Kingdom)

    2013-10-01

    Purpose: To test whether reducing radiation dose to uninvolved bladder while maintaining dose to the tumor would reduce side effects without impairing local control in the treatment of muscle-invasive bladder cancer. Methods and Materials: In this phase III multicenter trial, 219 patients were randomized to standard whole-bladder radiation therapy (sRT) or reduced high-dose volume radiation therapy (RHDVRT) that aimed to deliver full radiation dose to the tumor and 80% of maximum dose to the uninvolved bladder. Participants were also randomly assigned to receive radiation therapy alone or radiation therapy plus chemotherapy in a partial 2 × 2 factorial design. The primary endpoints for the radiation therapy volume comparison were late toxicity and time to locoregional recurrence (with a noninferiority margin of 10% at 2 years). Results: Overall incidence of late toxicity was less than predicted, with a cumulative 2-year Radiation Therapy Oncology Group grade 3/4 toxicity rate of 13% (95% confidence interval 8%, 20%) and no statistically significant differences between groups. The difference in 2-year locoregional recurrence free rate (RHDVRT − sRT) was 6.4% (95% confidence interval −7.3%, 16.8%) under an intention to treat analysis and 2.6% (−12.8%, 14.6%) in the “per-protocol” population. Conclusions: In this study RHDVRT did not result in a statistically significant reduction in late side effects compared with sRT, and noninferiority of locoregional control could not be concluded formally. However, overall low rates of clinically significant toxicity combined with low rates of invasive bladder cancer relapse confirm that (chemo)radiation therapy is a valid option for the treatment of muscle-invasive bladder cancer.

  17. An unusual case of haemoperitonium and bladder invasion due to placenta percreta in the third trimester mimicking threatened uterine rupture

    Directory of Open Access Journals (Sweden)

    Shama Khan

    2016-02-01

    Full Text Available Placenta praevia percreta is a rare but potentially lethal complication of pregnancy. It has an increasing clinical significance due to its association with previous caesarian section and uterine curettage. Herein we report a patient with placenta percreta, presenting in the emergency as 33 weeks of gestation with acute pain in abdomen and haemorrhagic shock, mimicking silent spontaneous uterine rupture, managed by emergency caesarian section followed by cesarian hysterectomy and bladder repair. [Int J Reprod Contracept Obstet Gynecol 2016; 5(2.000: 556-558

  18. Expression of GLUT1 is associated with increasing grade of malignancy in non-invasive and invasive urothelial carcinomas of the bladder

    Science.gov (United States)

    REIS, HENNING; TSCHIRDEWAHN, STEPHAN; SZARVAS, TIBOR; RÜBBEN, HERBERT; SCHMID, KURT WERNER; GRABELLUS, FLORIAN

    2011-01-01

    Glucose Transporter 1 (GLUT1) belongs to the expanding mammalian facilitative glucose transporter family. Elevated GLUT1 protein expression has been observed in the majority of urothelial carcinomas, with various effects on clinicopathological parameters. Whereas malignant cells have an accelerated metabolism with increased energy requirements, the membranous expression of GLUTs is amplified. GLUT1 protein expression was evaluated in urothelial tumours of increasing grade of malignancy, supplemented by a tumour proliferation analysis. Particular attention was paid to non-invasive precursors of urothelial carcinoma. A total of 105 paraffin-embedded samples were classified (normal urothelium, low/high-grade papillary carcinoma, carcinoma in situ and invasive carcinoma). Grading and staging were conducted using the 1998 ISUP/2004 WHO criteria. The staining intensity of GLUT1 was assessed with a standard immunoreactive score (IRS). The Ki-67 index was assessed by counting positive nuclei in representative urothelial hot spots. Results showed that an increased GLUT1-IRS and mean count of Ki-67-positive cells were significantly associated with an increased grade of malignancy (p<0.0001), particularly in non-invasive tumours. GLUT1-IRS was significantly associated with a Ki-67-labelled proliferative fraction (p<0.0001). No significant association regarding tumour grade or stage was observed within the invasive carcinoma group. GLUT1 protein expression was found to be strongly correlated with increased malignant potential, particularly in non-invasive urothelial carcinomas. The increase of GLUT1 expression may reflect a preinvasive metabolic switch in terms of enhanced cell metabolism concomitant to known genetic alterations. A further increase in invasive carcinomas may be related to hypoxic conditions. PMID:22848280

  19. Natural killer cell-based adoptive immunotherapy eradicates and drives differentiation of chemoresistant bladder cancer stem-like cells.

    Science.gov (United States)

    Ferreira-Teixeira, Margarida; Paiva-Oliveira, Daniela; Parada, Belmiro; Alves, Vera; Sousa, Vitor; Chijioke, Obinna; Münz, Christian; Reis, Flávio; Rodrigues-Santos, Paulo; Gomes, Célia

    2016-10-21

    High-grade non-muscle invasive bladder cancer (NMIBC) has a high risk of recurrence and progression to muscle-invasive forms, which seems to be largely related to the presence of tumorigenic stem-like cell populations that are refractory to conventional therapies. Here, we evaluated the therapeutic potential of Natural Killer (NK) cell-based adoptive immunotherapy against chemoresistant bladder cancer stem-like cells (CSCs) in a pre-clinical relevant model, using NK cells from healthy donors and NMIBC patients. Cytokine-activated NK cells from healthy donors and from high-grade NMIBC patients were phenotypically characterized and assayed in vitro against stem-like and bulk differentiated bladder cancer cells. Stem-like cells were isolated from two bladder cancer cell lines using the sphere-forming assay. The in vivo therapeutic efficacy was evaluated in mice bearing a CSC-induced orthotopic bladder cancer. Animals were treated by intravesical instillation of interleukin-activated NK cells. Tumor response was evaluated longitudinally by non-invasive bioluminescence imaging. NK cells from healthy donors upon activation with IL-2 and IL-15 kills indiscriminately both stem-like and differentiated tumor cells via stress ligand recognition. In addition to cell killing, NK cells shifted CSCs towards a more differentiated phenotype, rendering them more susceptible to cisplatin, highlighting the benefits of a possible combined therapy. On the contrary, NK cells from NMIBC patients displayed a low density on NK cytotoxicity receptors, adhesion molecules and a more immature phenotype, losing their ability to kill and drive differentiation of CSCs. The local administration, via the transurethral route, of activated NK cells from healthy donors provides an efficient tumor infiltration and a subsequent robust tumoricidal activity against bladder cancer with high selective cytolytic activity against CSCs, leading to a dramatic reduction in tumor burden from 80 % to complete

  20. Predicting recurrence and progression of non-muscle-invasive bladder cancer in Korean patients: a comparison of the EORTC and CUETO models.

    Science.gov (United States)

    Choi, Se Young; Ryu, Jae Hyung; Chang, In Ho; Kim, Tae-Hyoung; Myung, Soon Chul; Moon, Young Tae; Kim, Kyung Do; Kim, Jin Wook

    2014-10-01

    This study aimed to confirm the utility of the European Organization for Research and Treatment of Cancer (EORTC) and the Spanish Urological Club for Oncological Treatment (CUETO) scoring systems and to determine which model is preferred as a prognostic model in Korean patients with non-muscle-invasive bladder cancer. Between 1985 and 2011, 531 patients who were treated by transurethral resection of bladder cancer were retrospectively analyzed by use of the EORTC and CUETO models. Statistically, we performed Kaplan-Meier survival analysis; calculated Harrell's concordance index, receiver operating characteristic (ROC) curve, and cutoff values; and performed univariate and multivariate Cox proportional hazards regression analyses. For risk of recurrence, with the use of the EORTC model, all groups had statistically significant differences except between the group with a score of 0 and the group with a score of 1-4. With the use of the CUETO model, all groups differed significantly. For risk of progression, with the use of the EORTC model, significant differences were observed between all groups except between the group with a score of 2-6 and the group with a score of 7-13. With the use of the CUETO model, a significant difference was observed between the group with a score of 0 and the other groups. The concordance index of the EORTC and CUETO models was 0.759 and 0.836 for recurrence and 0.704 and 0.745 for progression, respectively. The area under the ROC curve for the EORTC and CUETO models was 0.832 and 0.894 for recurrence and 0.722 and 0.724 for progression, respectively. Both scoring systems, especially the CUETO model, showed value in predicting recurrence and progression in Korean patients, which will help in individualizing treatment and follow-up schedules.

  1. Administration of Mycobacterium phlei cell wall-nucleic acid complex in the immediate postoperative period for the treatment of non-muscle-invasive bladder cancer

    Science.gov (United States)

    Morales, Álvaro

    2016-01-01

    Introduction: This review sought to investigate the safety of intravesical administration of Mycobacterium phlei cell wall-nucleic acid (MCNA) in the immediate postoperative period after biopsy/resection for non-muscle-invasive bladder cancer (NMIBC). Methods: Patients with NMIBC who failed bacillus Calmette-Guérin (BCG) therapy and at high risk of recurrence and progression participated in this study. Treatment involved an induction phase of six weeks and maintenance of three weekly instillations every six months for two years. Biopsies were mandatory at six months and resections/biopsies as indicated. Of the 129 patients enrolled, 18 (14%) received one or more instillations of MCNA within 24 hours of an endoscopic procedure for a total of 32 instillations. Results: Fourteen patients (78%) received MCNA in the immediate postoperative period. Two (11%) received treatment the day after surgery, but a second treatment immediately after a transurethral resection of the bladder tumour (TURBT). The remaining two patients received an instillation each the day after surgery. Adverse events (AEs) occurred in 31.3% of those treated immediately after the procedure; they were mild, limited to the lower urinary tract, and not drug-related. Only one patient experienced systemic symptoms of moderate severity. None of the AEs resulted in postponement of treatment. There were no AEs among those receiving MCNA the day after surgery. Conclusions: The dual mechanism of action of MCNA suggests that early treatment would take advantage of its chemotherapeutic (pro-apoptotic) activity. Concerns about early administration due to the presence of live bacteria are circumvented with this sterile preparation. These preliminary results warrant further investigation to confirm the safety of perioperative administration of MCNA. PMID:27800054

  2. Retinoblastoma protein expression is an independent predictor of both radiation response and survival in muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Agerbaek, M; Alsner, J; Marcussen, N

    2003-01-01

    The objective of the study was to investigate the predictive value of various clinical, biochemical, and histopathological parameters, with special emphasis on the expression of the retinoblastoma protein (pRB), on the radiation response in bladder cancer. In order to obtain a truly objective....... Expression of pRB was assessed by immunohistochemical staining as present or absent. Complete response to radiotherapy was obtained in 42 of 106 evaluable patients (40%). Predictive for CR to radiotherapy, in univariate analysis, was transurethral resection (as opposed to biopsy), B-haemoglobin, no upper...... urinary retention, and loss of pRB staining. Loss of pRB staining was the strongest independent predictor of radiation response in multivariate logistic regression analysis and absence of upper urinary retention was the only other significant factor. Loss of pRB was the only parameter showing...

  3. Dynamic contrast-enhanced MRI in patients with muscle-invasive transitional cell carcinoma of the bladder can distinguish between residual tumour and post-chemotherapy effect

    Energy Technology Data Exchange (ETDEWEB)

    Donaldson, Stephanie B., E-mail: Stephanie.donaldson1@nhs.net [School of Cancer and Enabling Sciences, University of Manchester, Oxford Road, Manchester M13 9PL (United Kingdom); Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX (United Kingdom); Bonington, Suzanne C., E-mail: suzi.bonington@christie.nhs.uk [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX (United Kingdom); Kershaw, Lucy E., E-mail: lucy.kershaw@christie.nhs.uk [Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX (United Kingdom); Cowan, Richard, E-mail: richard.cowan@christie.nhs.uk [Department of Clinical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX (United Kingdom); Lyons, Jeanette, E-mail: jeanette.lyons@christie.nhs.uk [Department of Clinical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX (United Kingdom); Elliott, Tony, E-mail: tony.elliott@christie.nhs.uk [Department of Clinical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX (United Kingdom); Carrington, Bernadette M., E-mail: bernadette.carrington@christie.nhs.uk [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX (United Kingdom)

    2013-12-01

    Introduction: Treatment of muscle-invasive bladder cancer with chemotherapy results in haemorrhagic inflammation, mimicking residual tumour on conventional MR images and making interpretation difficult. The aim of this study was to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to estimate descriptive and tracer kinetic parameters post-neoadjuvant chemotherapy and to investigate whether parameters differed in areas of residual tumour and chemotherapy-induced haemorrhagic inflammation (treatment effect, Tr-Eff). Methods and materials: Twenty-one patients underwent DCE-MRI scans with 2.5 s temporal resolution before and following neoadjuvant chemotherapy. Regions-of-interest (ROIs) were defined in areas suspicious of residual tumour on T{sub 2}-weighted MRI scans. Data were analysed semi-quantitatively and with a two-compartment exchange model to obtain parameters including relative signal intensity (rSI{sub 80s}) and plasma perfusion (F{sub p}) respectively. The bladder was subsequently examined histologically after cystectomy for evidence of residual tumour and/or Tr-Eff. Differences in parameters measured in areas of residual tumour and Tr-Eff were examined using Student's t-test. Results: Twenty-four abnormal sites were defined after neoadjuvant chemotherapy. On pathology, 10 and 14 areas were identified as residual tumour and Tr-Eff respectively. Median rSI{sub 80s} and F{sub p} were significantly higher in areas of residual tumour than Tr-Eff (rSI{sub 80s} = 2.9 vs 1.7, p < 0.001; F{sub p} = 20.7 vs 9.1 ml/100 ml/min, p = 0.03). The sensitivity and specificity for differentiating residual tumour from Tr-Eff were 70% and 100% (rSI{sub 80s}), 60% and 86% (F{sub p}), and 75% and 100% when combined. Conclusion: DCE-MRI parameters obtained post-treatment are capable of distinguishing between residual tumour and treatment effect in patients treated for bladder cancer with neoadjuvant chemotherapy.

  4. Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer

    DEFF Research Database (Denmark)

    Wiklund, Erik D; Bramsen, Jesper B; Hulf, Toby

    2011-01-01

    MicroRNAs (miRNA) are small noncoding RNAs commonly deregulated in cancer. The miR-200 family (miR-200a, -200b, -200c, -141 and -429) and miR-205 are frequently silenced in advanced cancer and have been implicated in epithelial to mesenchymal transition (EMT) and tumor invasion by targeting the t...

  5. Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer

    DEFF Research Database (Denmark)

    Wiklund, Erik D; Bramsen, Jesper B; Hulf, Toby

    2011-01-01

    MicroRNAs (miRNA) are small noncoding RNAs commonly deregulated in cancer. The miR-200 family (miR-200a, -200b, -200c, -141 and -429) and miR-205 are frequently silenced in advanced cancer and have been implicated in epithelial to mesenchymal transition (EMT) and tumor invasion by targeting...

  6. Non-muscle contractile proteins in the organ of corti

    Energy Technology Data Exchange (ETDEWEB)

    Thalmann, I.; Giometti, C.S.; Thalmann, R. (Washington Univ., St. Louis, MO (USA))

    1985-01-01

    Evidence indicates that an active contractile process exists in the outer hair cells of the mammalian cochlea. Proteins ordinarily associated with muscle contraction have been identified in the outer hair cells by immunohistologic techniques. On this basis a muscle-like mechanism of contraction/relaxation has been postulated by several investigators. The possibility must be considered, however, that the contractile proteins identified thus far in inner ear structures may be nonmuscle rather than muscle forms. In skeletal muscle, actin and myosin are responsible for the physical movement of the muscle fibers, and tropomyosin and troponin are involved in regulating this movement; these four proteins, as well as a variety of proteins involved with the normal cell maintenance functions are all of a muscle-specific type. Non-muscle-like motion also depends upon the interaction of actin with myosin; however, not only are these proteins structurally different from those specific to skeletal muscle but their proportions are also different. We have used two-dimensional polyacrylamide gel electrophoresis to study the proteins in freeze dried preparations of whole organ of Corti from the guinea pig. The identified proteins include non-muscle actin, three forms of non-muscle tropomyosin, alpha- and beta-tubulin, alpha-actinin, and lactate dehydrogenase (LDH B). Myosin heavy and light chains were not detected in the organ of Corti preparation, but the levels of those proteins might be too low to be detected with the protein load used of those proteins might be too low to be detected with the protein load used for this analysis. Although troponin could not be detected, calmodulin was present. All of these findings tend to indicate that the contraction/relaxation processes that have been associated with the organ of Corti by others are of the non-muscle variety.

  7. The Patient Deficit Model Overturned: a qualitative study of patients' perceptions of invitation to participate in a randomized controlled trial comparing selective bladder preservation against surgery in muscle invasive bladder cancer (SPARE, CRUK/07/011).

    Science.gov (United States)

    Moynihan, Clare; Lewis, Rebecca; Hall, Emma; Jones, Emma; Birtle, Alison; Huddart, Robert

    2012-11-29

    Evidence suggests that poor recruitment into clinical trials rests on a patient 'deficit' model - an inability to comprehend trial processes. Poor communication has also been cited as a possible barrier to recruitment. A qualitative patient interview study was included within the feasibility stage of a phase III non-inferiority Randomized Controlled Trial (RCT) (SPARE, CRUK/07/011) in muscle invasive bladder cancer. The aim was to illuminate problems in the context of randomization. The qualitative study used a 'Framework Analysis' that included 'constant comparison' in which semi-structured interviews are transcribed, analyzed, compared and contrasted both between and within transcripts. Three researchers coded and interpreted data. Twenty-four patients agreed to enter the interview study; 10 decliners of randomization and 14 accepters, of whom 2 subsequently declined their allocated treatment.The main theme applying to the majority of the sample was confusion and ambiguity. There was little indication that confusion directly impacted on decisions to enter the SPARE trial. However, confusion did appear to impact on ethical considerations surrounding 'informed consent', as well as cause a sense of alienation between patients and health personnel.Sub-optimal communication in many guises accounted for the confusion, together with the logistical elements of a trial that involved treatment options delivered in a number of geographical locations. These data highlight the difficulty of providing balanced and clear trial information within the UK health system, despite best intentions. Involvement of multiple professionals can impact on communication processes with patients who are considering participation in RCTs. Our results led us to question the 'deficit' model of patient behavior. It is suggested that health professionals might consider facilitating a context in which patients feel fully included in the trial enterprise and potentially consider alternatives to

  8. The Patient Deficit Model Overturned: a qualitative study of patients' perceptions of invitation to participate in a randomized controlled trial comparing selective bladder preservation against surgery in muscle invasive bladder cancer (SPARE, CRUK/07/011

    Directory of Open Access Journals (Sweden)

    Moynihan Clare

    2012-11-01

    Full Text Available Abstract Background Evidence suggests that poor recruitment into clinical trials rests on a patient ‘deficit’ model – an inability to comprehend trial processes. Poor communication has also been cited as a possible barrier to recruitment. A qualitative patient interview study was included within the feasibility stage of a phase III non-inferiority Randomized Controlled Trial (RCT (SPARE, CRUK/07/011 in muscle invasive bladder cancer. The aim was to illuminate problems in the context of randomization. Methods The qualitative study used a ‘Framework Analysis’ that included ‘constant comparison’ in which semi-structured interviews are transcribed, analyzed, compared and contrasted both between and within transcripts. Three researchers coded and interpreted data. Results Twenty-four patients agreed to enter the interview study; 10 decliners of randomization and 14 accepters, of whom 2 subsequently declined their allocated treatment. The main theme applying to the majority of the sample was confusion and ambiguity. There was little indication that confusion directly impacted on decisions to enter the SPARE trial. However, confusion did appear to impact on ethical considerations surrounding ‘informed consent’, as well as cause a sense of alienation between patients and health personnel. Sub-optimal communication in many guises accounted for the confusion, together with the logistical elements of a trial that involved treatment options delivered in a number of geographical locations. Conclusions These data highlight the difficulty of providing balanced and clear trial information within the UK health system, despite best intentions. Involvement of multiple professionals can impact on communication processes with patients who are considering participation in RCTs. Our results led us to question the ‘deficit’ model of patient behavior. It is suggested that health professionals might consider facilitating a context in which patients

  9. Dysregulation of mammalian target of rapamycin pathway in plasmacytoid variant of urothelial carcinoma of the urinary bladder.

    Science.gov (United States)

    Gonzalez-Roibon, Nilda D; Chaux, Alcides; Al-Hussain, Turki; Osunkoya, Adeboye O; Bezerra, Stephania Martins; Hicks, Jessica; Epstein, Jonathan I; Netto, George J

    2013-04-01

    Plasmacytoid urothelial carcinoma is a rare but aggressive variant of bladder cancer with no clear therapeutic guidelines. Dysregulation of the mammalian target of rapamycin (mTOR) pathway has been linked to oncogenesis in conventional bladder cancer. Several antineoplastic agents targeting mTOR pathway are currently available. This study assesses mTOR pathway status as well as c-myc and p27 expression. We retrieved 19 archival cases of plasmacytoid urothelial carcinoma from two institutions. Whole tissue sections were evaluated for immunoexpression of phosphatase and tensin homolog (PTEN), phosphorylated mTOR, phosphorylated protein kinase B (AKT), phosphorylated S6, c-myc, and p27. We evaluated intensity (0 to 3+) and extent (0%-100%) of expression for all markers. An H score was calculated as the sum of products of intensity and extent for each marker and used during analysis. In addition, PTEN loss was defined as absence of expression in >10% of tumor cells. We encountered PTEN loss in 28%. Higher H score for nuclear phosphorylated AKT and a lower H score for phosphorylated S6 was encountered in muscle invasive tumors compared to non-muscle invasive tumors (P = .007 and P = .009, respectively). Although a trend for negative prognostic impact on overall survival for higher phosphorylated mTOR expression was noted (P = .051), markers expression levels failed to predict survival in our cohort. We found dysregulation of mTOR pathway members in urinary bladder plasmacytoid urothelial carcinoma, suggesting that the use of mTOR pathway inhibitors might be beneficial for patients with this aggressive tumor.

  10. Pathologic Response Rates of Gemcitabine/Cisplatin versus Methotrexate/Vinblastine/Adriamycin/Cisplatin Neoadjuvant Chemotherapy for Muscle Invasive Urothelial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Franklin C. Lee

    2013-01-01

    Full Text Available Objectives. To compare pathologic outcomes after treatment with gemcitabine and cisplatin (GC versus methotrexate, vinblastine, adriamycin, and cisplatin (MVAC in the neoadjuvant setting. Methods. Data was retrospectively collected on 178 patients with T2-T4 bladder cancer who underwent radical cystectomy between 2003 and 2011. Outcomes of interest included those with complete response (pT0 and any response (≤pT1. Odds ratios were calculated using multivariate logistic regression. Results. Compared to those who did not receive neoadjuvant chemotherapy, there were more patients with complete response (28% versus 9%, OR 3.11 (95% CI: 1.45–6.64, P=0.03 and any response (52% versus 25%, OR 3.23 (95% CI: 1.21–8.64, P=0.01. Seventy-two patients received GC (n=41 or MVAC (n=31. CR was achieved in 29% and 22% of GC and MVAC patients, respectively (multivariate OR 0.39, 95% CI 0.10–1.58. Any response (≤pT1 was achieved in 56% of GC and 45% of MVAC patients (multivariate OR 0.45, 95% CI 0.12–1.71. Conclusions. We observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of patients with muscle invasive urothelial cancer (MIBC. Our findings support the use of GC as an alternative regimen in the neoadjuvant setting.

  11. Prognostic value of Bcl-2 and Bax tumor cell expression in patients with non muscle-invasive bladder cancer receiving bacillus Calmette-Guerin immunotherapy.

    Science.gov (United States)

    Ajili, Faouzia; Kaabi, Belhassen; Darouiche, Amine; Tounsi, Haifa; Kourda, Nadia; Chebil, Mohamed; Manai, Mohamed; Boubaker, Samir

    2012-02-01

    Apoptosis is the distinctive form of programmed cell death that complements cell proliferation in maintaining normal tissue homeostasis. The significance of constitutive apoptosis in the recurrence of Non Muscle Invasive Bladder Cancer has yet to be investigated. The aim of this study is to investigate the prognostic significance of Bax and Bcl-2 in terms of recurrence after BCG immunotherapy. Immunohistochemical analysis was performed on frozen biopsies to evaluate bcl-2 and Bax proteins expression in 28 cases of NMIBC. All patients with confirmed NMIBC were treated with intravesical BCG-immunotherapy. The follow up was performed for 26 months. The correlation between clinicopathological, immunohistochemical data and the response to BCG therapy was performed. Univariate analysis showed that, PT1 stage, High grade and Bax expression increased significantly the risk of recurrence (P = 0.015, P = 0.015 and P= 0.034 respectively). In addition, multivariate analysis selected the model involving stage, age, Bax and Bcl-2 expression as the best independent variables of recurrence. In conclusion, the expression of Bcl-2 and Bax in NMIBC could have a prognostic value in assessing the risk of recurrence after BCG immunotherapy. These findings require further investigations on larger cohort in order to ascertain new molecular markers of the response to BCG immunotherapy.

  12. Bladder exstrophy repair

    Science.gov (United States)

    Bladder birth defect repair; Everted bladder repair; Exposed bladder repair; Repair of bladder exstrophy ... Bladder exstrophy repair involves two surgeries. The first surgery is to repair the bladder and the second one is to attach ...

  13. Bladder Stones

    Science.gov (United States)

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

  14. Production of the Escherichia coli common pilus by uropathogenic E. coli is associated with adherence to HeLa and HTB-4 cells and invasion of mouse bladder urothelium.

    Directory of Open Access Journals (Sweden)

    Zeus Saldaña

    Full Text Available Uropathogenic Escherichia coli (UPEC strains cause urinary tract infections and employ type 1 and P pili in colonization of the bladder and kidney, respectively. Most intestinal and extra-intestinal E. coli strains produce a pilus called E. coli common pilus (ECP involved in cell adherence and biofilm formation. However, the contribution of ECP to the interaction of UPEC with uroepithelial cells remains to be elucidated. Here, we report that prototypic UPEC strains CFT073 and F11 mutated in the major pilin structural gene ecpA are significantly deficient in adherence to cultured HeLa (cervix and HTB-4 (bladder epithelial cells in vitro as compared to their parental strains. Complementation of the ecpA mutant restored adherence to wild-type levels. UPEC strains produce ECP upon growth in Luria-Bertani broth or DMEM tissue culture medium preferentially at 26°C, during incubation with cultured epithelial cells in vitro at 37°C, and upon colonization of mouse bladder urothelium ex vivo. ECP was demonstrated on and inside exfoliated bladder epithelial cells present in the urine of urinary tract infection patients. The ability of the CFT073 ecpA mutant to invade the mouse tissue was significantly reduced. The presence of ECP correlated with the architecture of the biofilms produced by UPEC strains on inert surfaces. These data suggest that ECP can potentially be produced in the bladder environment and contribute to the adhesive and invasive capabilities of UPEC during its interaction with the host bladder. We propose that along with other known adhesins, ECP plays a synergistic role in the multi-step infection of the urinary tract.

  15. A non-invasive technique for standing surgical repair of urinary bladder rupture in a post-partum mare: a case report

    Directory of Open Access Journals (Sweden)

    Stephen JO

    2009-11-01

    Full Text Available Abstract An 11-year-old mare presented 36 hours after foaling with a ruptured bladder. Uroperitoneum was diagnosed on ultrasound and from the creatinine concentration of the peritoneal fluid. Bladder endoscopy demonstrated tissue necrosis and a rent in the dorsocranial aspect of the bladder. Following stabilisation, including abdominal drainage and lavage, the mare was taken to standing surgery. Under continuous sedation and epidural anaesthesia, and after surgical preparation, a Balfour retractor was placed in the vagina. Using sterile lubricant and moderate force, it was possible to insert a hand into the bladder. The tear was easily palpable on the dorsal portion of the bladder. Two fingers were inserted through the tear and used to provide traction to evert the bladder completely into the vagina where it could grasped with the surgeons other hand to prevent further trauma. A second surgeon could then visualise the entire tear and repaired this using a single layer of size zero PDS suture in a single continuous pattern. As soon as the bladder was repaired, it was replaced via the urethra. The mare did well after surgery and was discharged after 48 hours, apparently normal. This report is the first describing repair of the bladder without an abdominal incision or incision into the urethral sphincter. This greatly reduces the chance of possible complications such as urine pooling after surgery with the previously described standing technique or bladder trauma due to traction with abdominal surgery.

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

    Directory of Open Access Journals (Sweden)

    Roberto Sanseverino

    2016-07-01

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

  17. Determining optimal maintenance schedules for adjuvant intravesical bacillus Calmette-Guerin immunotherapy in non-muscle-invasive bladder cancer: a systematic review and network meta-analysis.

    Science.gov (United States)

    Huang, Zixiong; Liu, Huixin; Wang, Yizeng; Zhang, Chunfang; Xu, Tao

    2017-08-01

    To figure out optimal bacillus Calmette-Guerin (BCG) maintenance schedules for non-muscle-invasive bladder cancer (NMIBC) patients by comparing different schedules in a systematic review using conventional and network meta-analysis. Literature was searched in the databases of Medline, Embase, Cochrane library, Clinicaltrials.gov, Wanfang, CNKI and SinoMed in April 2016 and 9 randomized clinical trials comparing intravesical BCG maintenance therapy with BCG induction-only therapy or comparing different BCG maintenance schedules (induction-only, 1 year, 1.5 year, 2 year, 3 year maintenance) in NMIBC patients were included. Conventional and network meta-analyses within a Bayesian framework were performed to calculate odds ratios of tumor recurrence, progression and side effects (cystitis, hematuria, general malaise and fever). The surface under the cumulative ranking curve (SUCRA) mean ranking was used to obtain schedule hierarchy. Data from 1951 patients showed that longer-term maintenance BCG therapy does not significantly decrease tumor recurrence and progression rate of NMIBC compared to shorter-term maintenance BCG therapy. However, longer-maintenance therapy does not increase side effect incidence compared to induction-only therapy. According to SUCRA results, induction-only therapy has the highest probability of recurrence and progression but least probability of side effects. Longer BCG maintenance therapy (such as 3 years) is not superior to shorter maintenance therapy (such as 1 year). But maintenance therapy overall is better than induction-only BCG therapy while not increasing side effects. Though further evidence and clinical practice with balanced confounding factors (risk stratification and BCG strain) are wished for, the current study suggests the common use of 1 year intravesical BCG instillation for NMIBC patients.

  18. Combined Chemoradiation Therapy With Twice-Weekly Gemcitabine and Cisplatin for Organ Preservation in Muscle-Invasive Bladder Cancer: Long-Term Results of a Phase 1 Trial

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    Azria, David, E-mail: david.azria@icm.unicancer.fr [Department of Radiation Oncology and Radiophysics Unit, Montpellier Cancer Institute (ICM), Montpellier (France); INSERM, U896, IRCM, Montpellier (France); Riou, Olivier [Department of Radiation Oncology and Radiophysics Unit, Montpellier Cancer Institute (ICM), Montpellier (France); Rebillard, Xavier [Department of Urology, Clinique Beausoleil, Montpellier (France); Thezenas, Simon [Biostatistics Unit, Montpellier Cancer Institute, Montpellier (France); Thuret, Rodolphe [Department of Urology, Montpellier University Hospital, Montpellier (France); Fenoglietto, Pascal [Department of Radiation Oncology and Radiophysics Unit, Montpellier Cancer Institute (ICM), Montpellier (France); Pouessel, Damien; Culine, Stephane [Department of Medical Oncology, AP-HP Saint-Louis, Paris (France)

    2014-03-15

    Purpose: Concomitant treatment with radiation therapy and cisplatin (CDDP) remains the gold standard for bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC). We present the long-term results of a phase 1 clinical trial to assess the association of twice-weekly gemcitabine with CDDP and radiation therapy in this setting. Methods and Materials: Patients with pT2-pT4N0M0 MIBC without hydronephrosis or diffuse carcinoma in situ were enrolled in this study. After maximal transurethral resection of the bladder tumor, patients received concomitant radiation therapy (63 Gy in 1.8 fractions) and chemotherapy (CDDP 20 mg/m²/day over 4 days every 21 days and gemcitabine twice a week). The starting dose of gemcitabine was 15 mg/m² with dose escalation to 20, 25, and 30 mg/m². The primary endpoint was the maximum tolerated dose (MTD). Secondary endpoints included toxicity and tumor control. Results: Fourteen patients were enrolled. Dose-limiting toxicity occurred in 2 patients treated with 30 mg/m² gemcitabine (grade 4 thrombocytopenia and severe impairment of World Health Organization performance status, respectively). Nine patients received the complete chemoradiation therapy protocol. The recommended dose of gemcitabine was 25 mg/m². The median follow-up time was 53 months, and the overall and disease-specific 5-year survival rates were 62% and 77%, respectively. Among the patients who received the complete treatment, bladder-intact survival was 76% at 5 years, and the median overall survival was 69.6 months. Conclusions: This regimen was well tolerated. The gemcitabine MTD was 25 mg/m². Bladder preservation and disease control were promising. A multicenter phase 2 randomized trial is ongoing.

  19. Neurogenic Bladder

    Directory of Open Access Journals (Sweden)

    Peter T. Dorsher

    2012-01-01

    Full Text Available Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented.

  20. Bladder Retraining

    Science.gov (United States)

    ... Complicated IC Cases Promising IC Diagnostic Tests Wrong Diagnosis IC Treatment Guideline IC Treatments IC Diet & Self Management Physical Therapy Antidepressants Antihistamines Pentosan Polysulfate Sodium Bladder Instillations Immunosuppresants ...

  1. Bacillus Calmette Guerin induces fibroblast activation both directly and through macrophages in a mouse bladder cancer model.

    Directory of Open Access Journals (Sweden)

    Catalina Lodillinsky

    Full Text Available BACKGROUND: Bacillus Calmette-Guerin (BCG is the most effective treatment for non-muscle invasive bladder cancer. However, a failure in the initial response or relapse within the first five years of treatment has been observed in 20% of patients. We have previously observed that in vivo administration of an inhibitor of nitric oxide improved the response to BCG of bladder tumor bearing mice. It was described that this effect was due to a replacement of tumor tissue by collagen depots. The aim of the present work was to clarify the mechanism involved in this process. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that BCG induces NIH-3T3 fibroblast proliferation by activating the MAPK and PI3K signaling pathways and also differentiation determined by alpha-smooth muscle actin (alpha-SMA expression. In vivo, intratumoral inoculation of BCG also increased alpha-SMA and collagen expression. Oral administration of L-NAME enhanced the pro-fibrotic effect of BCG. Peritoneal macrophages obtained from MB49 tumor-bearing mice treated in vivo with combined treatment of BCG with L-NAME also enhanced fibroblast proliferation. We observed that FGF-2 is one of the factors released by BCG-activated macrophages that is able to induce fibroblast proliferation. The involvement of FGF-2 was evidenced using an anti-FGF2 antibody. At the same time, this macrophage population improved wound healing rate in normal mice and FGF-2 expression was also increased in these wounds. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that fibroblasts are targeted by BCG both directly and through activated macrophages in an immunotherapy context of a bladder murine model. We also described, for the first time, that FGF-2 is involved in a dialog between fibroblasts and macrophages induced after BCG treatment. The fact that L-NAME administration improves the BCG effect on fibroblasts, NO inhibition, might represent a new approach to add to the conventional BCG therapy.

  2. Invasively estimated international continence society obstruction classification versus noninvasively assessed bladder outlet obstruction probability in treatment recommendation for LOTS suggestive of BPH

    NARCIS (Netherlands)

    Boormans, Joost L.; van Venrooij, Ger E. P. M.; Boon, Tom A.

    2007-01-01

    OBJECTIVES To investigate the contribution of urodynamically proven presence or absence (International Continence Society classification) of bladder outlet obstruction (BOO) to treatment recommendations for lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia, and to invest

  3. Kinetic characterization of the sole nonmuscle myosin-2 from the model organism Drosophila melanogaster.

    Science.gov (United States)

    Heissler, Sarah M; Chinthalapudi, Krishna; Sellers, James R

    2015-04-01

    Nonmuscle myosin-2 is the primary enzyme complex powering contractility of the F-actin cytoskeleton in the model organism Drosophila. Despite myosin's essential function in fly development and homeostasis, its kinetic features remain elusive. The purpose of this in vitro study is a detailed steady-state and presteady-state kinetic characterization of the Drosophila nonmuscle myosin-2 motor domain. Kinetic features are a slow steady-state ATPase activity, high affinities for F-actin and ADP, and a low duty ratio. Comparative analysis of the overall enzymatic signatures across the nonmuscle myosin-2 complement from model organisms indicates that the Drosophila protein resembles nonmuscle myosin-2s from metazoa rather than protozoa, though modulatory aspects of myosin motor function are distinct. Drosophila nonmuscle myosin-2 is uniquely insensitive toward blebbistatin, a commonly used myosin-2 inhibitor. An in silico modeling approach together with kinetic studies indicate that the nonconsensus amino acid Met466 in the Drosophila nonmuscle myosin-2 active-site loop switch-2 acts as blebbistatin desensitizer. Introduction of the M466I mutation sensitized the protein for blebbistatin, resulting in a half-maximal inhibitory concentration of 36.3 ± 4.1 µM. Together, these data show that Drosophila nonmuscle myosin-2 is a bona fide molecular motor and establish an important link between switch-2 and blebbistatin sensitivity.

  4. ESR1, ERBB2, and Ki67 mRNA expression predicts stage and grade of non-muscle-invasive bladder carcinoma (NMIBC).

    Science.gov (United States)

    Breyer, Johannes; Wirtz, Ralph M; Laible, Mark; Schlombs, Kornelia; Erben, Philipp; Kriegmair, Maximilian Christian; Stoehr, Robert; Eidt, Sebastian; Denzinger, Stefan; Burger, Maximilian; Hartmann, Arndt; Otto, Wolfgang

    2016-11-01

    Pathological staging and grading are crucial for risk assessment in non-muscle-invasive bladder cancer (NMIBC). Molecular grading might support pathological evaluation and minimize interobserver variability. In this study, the well-established breast cancer markers ESR1, PGR, ERBB2, and MKI67 were evaluated as potential molecular markers to support grading and staging in NMIBC. We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with NMIBC. Messenger RNA (mRNA) expression of the aforementioned markers was measured by single-step reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) using RNA-specific TaqMan assays. Relative gene expression was determined by normalization to two reference genes (CALM2 and B2M) using the 40(-ΔΔCT) method and correlated to histopathological stage and grade. Pathological assessment was performed by an experienced uropathologist. Statistical analysis was performed using the SAS software JMP 9.0.0 version and GraphPad Prism 5.04. Of 381 cases of NMIBC, samples of 100 pTa and 255 pT1 cases were included in the final study. Spearman rank correlation revealed significant correlations between grade and expression of MKI67 (r = 0.52, p < 0.0001), ESR1 (r = 0.25, p < 0.0001), and ERBB2 (r = 0.18, p = 0.0008). In Mann-Whitney tests, MKI67 was significantly different between all grades (p < 0.0001), while ESR1 (p = 0.0006) and ERBB2 (p = 0.027) were significantly different between G2 and G3. Higher expression of MKI67 (r = 0.49; p < 0.0001), ERBB2 (r = 0.22; p < 0.0001), and ESR1 (r = 0.18; p = 0.0009) mRNA was positively correlated with higher stage. MKI67 (p < 0.0001), ERBB2 (p = 0.0058), and PGR (p = 0.0007) were significantly different between pTa and pT1. In NMIBC expression of ESR1, ERBB2 and MKI67 are significantly different between stage and grade. This potentially provides objective parameters for pathological

  5. 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

  6. Anesthesia for trans-sternal thymectomy: modified non-muscle relaxant technique.

    Science.gov (United States)

    Baftiu, Nehat; Hadri, Burhan; Morina, Muharrem; Mustafa, Aziz

    2011-01-01

    Anesthesia for thymectomy in myasthenia gravis is challenging. Early surgical management is now considered to be an important therapeutic intervention for most of the patients of myasthenia gravis. The anesthetic experience of that technique is quite large. It involves either muscle relaxant or non-muscle relaxant techniques. However, the literature is deficient of standard anesthetic technique for thymectomy. Therefore we present in this report a modified non-muscle relaxant technique for thymectomy. We report one case with thymectomy under general anesthesia using fentanyl and propofol for induction and endotracheal intubation using non-muscle relaxant technique. The intubating, intraoperative and postoperative conditions were excellent.

  7. Utility of Clinical Risk Stratification in the Selection of Muscle-Invasive Bladder Cancer Patients for Neoadjuvant Chemotherapy: A Retrospective Cohort Study

    Science.gov (United States)

    von Rundstedt, Friedrich-Carl; Mata, Douglas A.; Kryvenko, Oleksandr N.; Shah, Anup A.; Jhun, Iny; Lerner, Seth P.

    2016-01-01

    Introduction: Level I evidence supports the use of cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer prior to radical cystectomy (RC). On average, 30–40% of patients achieve a complete pathologic response (i.e., stage pT0) after receiving NAC. Some centers risk-stratify patients, suggesting that there may be a higher-risk population that would derive the most benefit from NAC. Recently, a risk-stratification model developed at M.D. Anderson Cancer Center (MDACC) specified criteria for clinical staging and patient selection for NAC. We applied this model to our own RC patient cohort and evaluated our own experience with clinical risk stratification and the effect of NAC on post treatment risk categories. Methods: We retrospectively reviewed the charts of consecutive patients who underwent RC at two institutions between 2004 and 2014 and noted whether or not they received NAC. We determined the clinical stage by reviewing the exam under anesthesia, transurethral resection biopsy (TURBT) pathology, and preoperative imaging. Patients with cT2-T4a node-negative disease were included. Those with sarcomatoid features or adenocarcinoma were excluded. Patients were classified as high risk if they had tumor-associated hydronephrosis, clinical stage≥T3b-T4a disease, variant histology (i.e., micropapillary or small cell), or lymphovascular invasion (LVI), as specified by the MDACC model. Variables were examined for associations with cancer-specific survival (CSS), overall survival (OS), and risk-category reclassification. Results: We identified 166 patients with a median follow-up time of 22.2 months. In all, 117 patients (70.5%) did not receive NAC, 68 (58.1%) of whom we classified as high risk. Among patients not receiving NAC, CSS and OS were significantly decreased in high-risk patients (log-rank test p = 0.01 for both comparisons). The estimated age-adjusted hazard ratios of high-risk classification for cancer-specific and overall

  8. EPO gene expression induces the proliferation, migration and invasion of bladder cancer cells through the p21WAF1‑mediated ERK1/2/NF-κB/MMP-9 pathway.

    Science.gov (United States)

    Park, Sung Lyea; Won, Se Yeon; Song, Jun-Hui; Kim, Wun-Jae; Moon, Sung-Kwon

    2014-11-01

    Erythropoietin (EPO) is a cytokine that modulates the production of red blood cells. Previous studies have contradicted the assumed role of EPO in tumor cell proliferation. In the present study, we investigated the effect of EPO in the proliferation, migration and invasion that is involved in the signaling pathways and cell-cycle regulation of bladder cancer 5637 cells. The results showed that an overexpression of the EPO gene has a potent stimulatory effect on DNA synthesis, migration and invasion. EPO gene expression increased the expression of matrix metalloproteinase (MMP)-9 via the binding activity of NF-κB, AP-1 and Sp-1 in 5637 cells. The transfection of 5637 cells with the EPO gene induced the phosphorylation of ERK1/2. Treatment with ERK1/2 inhibitor U0126 significantly inhibited the increased proliferation, migration and invasion of EPO gene-transfected cells. U0126 treatment suppressed the induction of MMP-9 expression through NF-κB binding activity in EPO gene transfectants. In addition, EPO gene expression was correlated with the upregulation of cyclins/CDKs and the upregulation of the CDK inhibitor p21WAF1 expression. Finally, the inhibition of p21WAF1 function by siRNA blocked the proliferation, migration, invasion and phosphorylation of ERK1/2 signaling, as well as MMP-9 expression and activation of NF-κB in EPO gene-transfected cells. These novel findings suggest that the molecular mechanisms of EPO contribute to the progression and development of bladder tumors.

  9. Uroflowmetry, trans rectal ultra sonography and power doppler to develop a less invasive bladder outlet obstruction score in benign prostatic hyperplasia: A prospective analysis

    Directory of Open Access Journals (Sweden)

    Rajiv Goyal

    2006-01-01

    Full Text Available OBJECTIVE : To evaluate the ability of transrectal power doppler sonography (TRPDS in combination with conventional grey scale transrectal ultrasonography (TRUS, uroflowmetry and clinical parameters, to predict bladder outlet obstruction (BOO in benign prostatic hyperplasia (BPH. MATERIALS AND METHODS : Sixty-nine male patients with more than 50 years of age, presenting with lower urinary tract symptoms were evaluated prospectively for BOO secondary to BPH. TRUS was done to estimate prostate volume (PV, transition zone volume (TZV, median lobe projection in the bladder (ML and bladder wall thickness (BWT. TRPDS was done to measure resistive index (RI of transition zone vessels. All patients also underwent PFS and depending upon its results, the patients were divided into Group 1 [Abram-Griffiths (AG number 40. Mean values of TRUS and TRPDS parameters and uroflowmetry in the two groups were compared to identify predictive factors for BOO. RESULTS : Demographic profile of Group 1 (n= 42 was similar to that of Group 2 (n= 27. Significant independent factors for prediction of BOO were maximum flow rate, resistive index of transition zone, median lobe projection into the bladder and post void residue. BOO scoring system was developed based on these 4 factors, which showed a specificity of 77.8% and a sensitivity of 85.7%, with an overall predictive value of 82.6%. CONCLUSIONS : Transrectal power doppler ultrasonography (resistive index in combination with uroflowmetry, median lobe projection in bladder and post void residue measurement can predict BOO with a high specificity and sensitivity.

  10. Prognostic significance of the 2004 WHO/ISUP classification for prediction of recurrence, progression, and cancer-specific mortality of non-muscle-invasive urothelial tumors of the urinary bladder: a clinicopathologic study of 1,515 cases.

    Science.gov (United States)

    Pan, Chin-Chen; Chang, Yen-Hwa; Chen, Kuang-Kuo; Yu, Hui-Jung; Sun, Chih-Hao; Ho, Donald M T

    2010-05-01

    To verify prognostic significance of the 2004 World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading systems, we retrospectively studied the tumors of 1,515 patients who underwent transurethral resection of primary non-muscle-invasive urothelial tumors (pTa, 1,006 patients; pT1, 509 patients) confined to the bladder. Cases were classified according to the 2004 WHO/ISUP systems as 212 cases of papillary urothelial neoplasm of low malignant potential (PUNLMP), 706 low-grade papillary urothelial carcinomas (LPUCs), and 597 high-grade papillary urothelial carcinomas (HPUCs). PUNLMP showed the statistically significantly lowest recurrence cumulative incidence compared with the other tumor types. There were significant differences and trends for higher progression and cancer-specific mortality cumulative incidence in the following order: PUNLMP, LPUC, pTa HPUC, and pT1 HPUC. No differences of progression and cancer-specific mortality cumulative incidence were found between pTa and pT1 LPUC. Our study validates the usefulness of the 2004 WHO/ISUP system to classify urothelial tumors into prognostically distinct categories that would contribute to the design of therapeutic and monitoring strategies for patients with non-muscle-invasive bladder urothelial tumors.

  11. Argininosuccinate Synthetase 1 Loss in Invasive Bladder Cancer Regulates Survival through General Control Nonderepressible 2 Kinase-Mediated Eukaryotic Initiation Factor 2α Activity and Is Targetable by Pegylated Arginine Deiminase.

    Science.gov (United States)

    Sahu, Divya; Gupta, Sounak; Hau, Andrew M; Nakashima, Kazufumi; Leivo, Mariah Z; Searles, Stephen C; Elson, Paul; Bomalaski, John S; Casteel, Darren E; Boss, Gerry R; Hansel, Donna E

    2016-12-09

    Loss of argininosuccinate synthetase 1 (ASS1), a key enzyme for arginine synthesis, occurs in many cancers, making cells dependent on extracellular arginine and targetable by the arginine-degrading enzyme pegylated arginine deiminase (ADI-PEG 20). We evaluated ASS1 expression and effects of ASS1 loss in bladder cancer which, despite affecting >70,000 people in the United States annually, has limited therapies. ASS1 loss was identified in conventional and micropapillary urothelial carcinoma, small cell, and squamous cell carcinoma subtypes of invasive bladder cancer, as well as in T24, J82, and UM-UC-3 but not in 5637, RT112, and RT4 cell lines. ASS1-deficient cells showed preferential sensitivity to ADI-PEG 20, evidenced by decreased colony formation, reduced cell viability, and increased sub-G1 fractions. ADI-PEG 20 induced general control nonderepressible 2-dependent eukaryotic initiation factor 2α phosphorylation and activating transcription factor 4 and C/EBP homologous protein up-regulation, associated with caspase-independent apoptosis and autophagy. These effects were ablated with selective siRNA silencing of these proteins. ASS1 overexpression in UM-UC-3 or ASS1 silencing in RT112 cells reversed these effects. ADI-PEG 20 treatment of mice bearing contralateral flank UM-UC-3 and RT112 xenografts selectively arrested tumor growth in UM-UC-3 xenografts, which had reduced tumor size, reduced Ki-67, and increased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. This suggests that ASS1 loss occurs in invasive bladder cancer and is targetable by ADI-PEG 20.

  12. Anesthesia for thoracoscopic thymectomy: modified non-muscle relaxant technique--case reports.

    Science.gov (United States)

    El-Dawlatly, Abdelazeem A

    2007-02-01

    Anesthesia for thymectomy in myasthenia gravis is challenging. The anesthetic experience of that technique is quite large. In involves either muscle relaxant or non-muscle relaxant techniques. However, the literature is deficient of standard anesthetic technique for thoracoscopic thymectomy. Therefore we present in this report a modified non-muscle relaxant technique for thoracoscopic thymectomy (TT). We report two cases who underwent TT under general anesthesia using sufentanil and propofol for induction and local anesthesia spray to the vocal cords to facilitate endobronchial intubation using non-muscle relaxant technique. The intubating, operating and postoperative conditions were excellent. To the best of our knowledge, this is the first report on modified non-muscle relaxant technique for TT in myasthenia gravis. Further cases have to be done to verify our technique.

  13. Overactive Bladder

    Science.gov (United States)

    ... social interactions and everyday activities. Causes Normal bladder function The kidneys produce urine, which drains into your ... Sleep disturbances and interrupted sleep cycles Issues with sexuality Your doctor might recommend treatment of associated conditions, ...

  14. Nonmuscle Myosin II helps regulate synaptic vesicle mobility at the Drosophila neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Qiu Xinping

    2010-03-01

    Full Text Available Abstract Background Although the mechanistic details of the vesicle transport process from the cell body to the nerve terminal are well described, the mechanisms underlying vesicle traffic within nerve terminal boutons is relatively unknown. The actin cytoskeleton has been implicated but exactly how actin or actin-binding proteins participate in vesicle movement is not clear. Results In the present study we have identified Nonmuscle Myosin II as a candidate molecule important for synaptic vesicle traffic within Drosophila larval neuromuscular boutons. Nonmuscle Myosin II was found to be localized at the Drosophila larval neuromuscular junction; genetics and pharmacology combined with the time-lapse imaging technique FRAP were used to reveal a contribution of Nonmuscle Myosin II to synaptic vesicle movement. FRAP analysis showed that vesicle dynamics were highly dependent on the expression level of Nonmuscle Myosin II. Conclusion Our results provide evidence that Nonmuscle Myosin II is present presynaptically, is important for synaptic vesicle mobility and suggests a role for Nonmuscle Myosin II in shuttling vesicles at the Drosophila neuromuscular junction. This work begins to reveal the process by which synaptic vesicles traverse within the bouton.

  15. Hexaminolevulinate-guided fluorescence cystoscopy in the diagnosis and follow-up of patients with non-muscle-invasive bladder cancer: review of the evidence and recommendations.

    NARCIS (Netherlands)

    Witjes, J.A.; Redorta, J.P.; Jacqmin, D.; Sofras, F.; Malmstrom, P.U.; Riedl, C.; Jocham, D.; Conti, G.; Montorsi, F.; Arentsen, H.C.; Zaak, D.; Mostafid, A.H.; Babjuk, M.

    2010-01-01

    CONTEXT: Compared with standard white-light cystoscopy, photodynamic diagnosis with blue light and the photosensitiser hexaminolevulinate has been shown to improve the visualisation of bladder tumours, reduce residual tumour rates by at least 20%, and improve recurrence-free survival. There is curre

  16. Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Galsky, Matthew D; Pal, Sumanta K; Chowdhury, Simon

    2015-01-01

    clinical T-classification 2 (cT2) through cT4aN0M0 urothelial cancer of the bladder and received neoadjuvant GC or methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) before undergoing cystectomy. Logistic regression was used to compute propensity scores as the predicted probabilities of patients...

  17. Results of the phase II EORTC 22971 trial evaluating combined accelerated external radiation and chemotherapy with 5FU and cisplatin in patients with muscle invasive transitional cell carcinoma of the bladder

    Energy Technology Data Exchange (ETDEWEB)

    Poortmans, Philip M. (Dept. of Radiation Oncology, Dr. Bernard Verbeeten Inst., Tilburg (NL)); Van Der Hulst, Marleen; Richaud, Pierre (Dept. of Radiation Oncology, Inst. Bergonieacute, Bordeaux (France)); Collette, Laurence; Pierart, Marianne (Statistics Dept., EORTC Data Center, Brussels (Belgium)); Ho Goey, S. (Dept. of Medical Oncology, TweeSteden Hospital, Tilburg (NL)); Bolla, Michel (Dept. of Radiation Oncology, CHU, Grenoble (France))

    2008-06-15

    Introduction. We prospectively evaluated concomitant radiotherapy and chemotherapy for advanced bladder cancer in a phase II EORTC trial to test whether it could be further studied as a potential treatment of bladder cancer. Patients and methods. Patients up to 75 years of age with invasive transitional-cell carcinoma of the bladder up to 5 cm, stage pT2 to pT3b, N0M0, without residual macroscopical tumour after transurethral excision were eligible. Radiotherapy consisted of 2 fractions of 1.2 Gy daily up to 60 Gy delivered in a period of 5 weeks. During the first and the last week, cisplatin 20 mg/m2/day and 5 FU 375 mg/m2/day were given concomitantly. Results. The study was interrupted early due to poor recruitment. Nine patients of the originally 43 planned were treated. Mean age was 63 years. Five patients had tumour stage pT2, 1 stage pT3a and 3 stage pT3b. All patients completed radiotherapy and chemotherapy as scheduled. Only one grade 3 and no grade 4 toxicity was seen. All patients were evaluated 3 months after treatment: eight patients had no detectable tumour and one had para-aortic lymph nodes. During further follow-up, a second patient got lymph node metastases and two patients developed distant metastases (lung in the patient with enlarged lymph nodes at the first evaluation and abdominal in one other). Those three patients died at respectively 19, 14, and 18 months after registration. Late toxicity was limited and often temporary. After 26 to 57 months of follow-up, no local recurrences were seen. Six patients remained alive without disease. Discussion. Despite the small cohort, this combination of concomitant chemotherapy and accelerated hyperfractionated radiotherapy for invasive bladder cancer seemed to be well tolerated and to result in satisfactory local control with limited early and late toxicity. It could therefore be considered for study in further clinical trials

  18. 经尿道膀胱肿瘤电切联合化疗治疗浸润性膀胱癌(附20例报告)%Efficacy of transurethral resection of bladder tumors in combination with chemotherapy in the treatment of invasive bladder cancer

    Institute of Scientific and Technical Information of China (English)

    王勇; 钟隆飞; 李巧星; 王伟录; 梁东彦; 吴久龙; 黄振华; 郑红芳; 单玉喜

    2014-01-01

    Objective To evaluate the clinical efficacy of transurethral resection of bladder tumor (TURBT)combined with intravesical chemotherapy and intravenous chemotherapy for inva-sive bladder cancer. Methods 20 patients,who were diagnosed with invasive bladder cancer by Imaging and pathology and not tolerating or refusing radical cystectomy were treated by TURBT.Of the 20 patients,the tumor diameters were 1.8 to 5.0 cm,11 cases were G2 and 9 cases were G3 , while TNM stage T2a 9 cases were in T2a stage,10 cases in T2b and 1 case in T4a stage.The tumors were resected to the bladder wall outer layer of fat,while transurethral resection of the prostate was simultaneous performed in 1 case with prostatic invasion.Postoperative GC schedule (gemcitabine +cisplatin)chemotherapy was implemented every three weeks as a cycle;Pirarubicin intravesical chemotherapy was administered once a week.Cystoscopy was performed every three months to as-sess the tumor recurrence. Results The tumors of 20 patients were resected completely.Opera-tive time ranged from 35 to 100 min,no serious complications occurred during the operation.The patients were confirmed as invasive transitional cell carcinoma by pathological examination.After chemotherapy,leukopenia appeared in four patients,and gastrointestinal reactions such as nausea or loss of appetite occurred in six patients,which were improved after symptomatic treatment.Patients were followed up from 3 to 24 months (average of 12 months).During the follow-up period,recurrence happened in three pa-tient after 6 months,12 months and 24 months respectively,while 1case died of bladder cancer metastasis. Conclusions TURBT in combination with chemotherapy is quite efficient for invasive bladder cancer patients and can be used as a compre-hensive treatment for bladder perservation.%目的:探讨经尿道膀胱肿瘤电切术(transurethral resection of bladder tumor, TURBT)联合膀胱灌注化疗及静脉化疗治疗浸润性膀胱癌的临床疗效

  19. MALIGNANT TUMORS OF THE BLADDER

    Directory of Open Access Journals (Sweden)

    Boris Sedmak

    2003-12-01

    Full Text Available Background. The incidence of bladder cancer is rising in Slovenia and in most countries in the World. Increasing incidence is probably due to aging population and risk factors. Approximately 75–85% of patients present with disease confined to mucosa (Ta-Tis, or submucosa (T1 stage. The other 15–25% have muscle invasion or nodal disease (stages T2-T4, N+ at presentation.Conclusions. The diagnosis of bladder cancer ultimately depends on cystoscopic examination of the bladder and histopathological evaluation of resected lesion. After transuretral resection (TUR treatment of superficial bladder tumors (TaT1 will be directed towards the prevention of recurrence and progression with bladder instillation of vaccine for tuberculosis (bacillus Calmette-Guerin-BCG or chemotherapeutic agents. Tumors of T2 or higher category are infiltrating tumors and cystectomy is necessary in the majority of cases. Incontinent or continent urinary diversion is presently considered after radical cystectomy. Contra-indications for cystectomy are major co-morbidity and patients not willing to accept the surgery. Bladder preservation with chemo and radiotherapy can be an option in these selected cases.

  20. Overactive Bladder.

    Science.gov (United States)

    White, Nicola; Iglesia, Cheryl B

    2016-03-01

    Overactive bladder (OAB) is a condition affecting millions of individuals in the United States. Anticholinergics are the mainstay of treatment. Bladder botulinum toxin injections have shown an improvement in symptoms of OAB equivalent to anticholinergic therapy. Percutaneous tibial nerve stimulation can decrease symptoms of urinary frequency and urge incontinence. Sacral neuromodulation for refractory patients has been approved by the Food and Drug Administration for treatment of OAB, urge incontinence, and urinary retention. Few randomized, head-to-head comparisons of the different available alternatives exist; however, patients now have increasing options to manage their symptoms and improve their quality of life.

  1. A Comparison of the Progression and Recurrence Risk Index in Non-Muscle-Invasive Bladder Tumors Detected by Narrow-Band Imaging Versus White Light Cystoscopy, Based on the EORTC Scoring System

    Directory of Open Access Journals (Sweden)

    Shadpour

    2016-01-01

    Full Text Available Background Transitional cell carcinoma of the bladder, the second most common urologic malignancy, is amenable to early diagnosis. This study presents the potential prognostic benefit for a less invasive modification to the standard endoscopic approach. Objectives To evaluate the risk index for the progression and recurrence of additional tumors detected with narrow-band imaging (NBI cystoscopy compared to standard white light imaging (WLI cystoscopy in non-muscle-invasive bladder cancer (NMIBC, based on the European organization for research and treatment of cancer (EORTC scoring system. Patients and Methods Patients with NMIBC, who were scheduled for resection between May 2012 and May 2013, were studied and mapped under NBI and WLI cystoscopy by independent surgeons prior to resection. Detection rates and tumor characteristics, including EORTC progression and the recurrence risk index, were compared. Results Fifty patients, aged 63.86 ± 10.05 years, were enrolled. The overall detection rate was 98.9% for NBI vs. 89.4% for WLI (P = 0.001, and the false-positive rates were 9.6% and 5.8%, respectively (P = 0.051. Ten tumors were detected by NBI alone, including four grade I tumors, four grade III tumors, and two carcinomas in situ. The tumor progression index was not significantly reduced with NBI compared to WLI (P > 0.05; however, the recurrence index was significantly lower in the NBI group (P < 0.05. Conclusions NBI cystoscopy improved the detection rate. Although false positives were more common with NBI, this was not statistically significant. NBI found additional aggressive tumors, which underscores the impact of detection in EORTC recurrence risk scoring.

  2. HpD Photobiology And Photodynamic Therapy Of Bladder Carcinoma

    Science.gov (United States)

    Lin, Chi-Wei

    1988-02-01

    Bladder carcinoma is considered one of the most favorable targets for the application of photodynamic therapy (PDT) due to the accessibility of the bladder for light delivery. Examination of the bladder and surgical procedures are routinely performed by the insertion of an optical instrument called cystoscope through the urethra. Thus, the treatment of bladder cancer by PDT can be conducted through the cystoscope with minimal invasion. However, to achieve optimal results from this treatment, one must consider both the structure of the bladder and the nature of the carcinoma.

  3. Radical cystectomy with orthotopic neobladder for invasive bladder cancer: a critical analysis of long term oncological, functional and quality of life results

    Directory of Open Access Journals (Sweden)

    Arnulf Stenzl

    2010-10-01

    Full Text Available PURPOSE: Analyze current knowledge and practice regarding tumor-related cystectomy with subsequent orthotopic neobladder both in male and female patients. DESIGN, SETTING, AND PARTICIPANTS: Evaluate literature predominantly from the last decade dealing with long-term experience in large numbers of patients with an orthotopic neobladder following cystectomy. Oncological outcome specific to an orthotopic neobladder, functional aspects such as urinary continence, renal function, sexual activity and other quality of life issues are elucidated. RESULTS: Local pelvic recurrences after urothelial bladder cancer occur in 7-12%. Urethral second primary tumors in male and female patients in contemporary series with bladder substitution are 4-6% and 1.4 o 4%, respectively. Upper tract recurrences vary between 2.4-17%. Complications regarding the upper urinary tract have dramatically diminished due to simplified forms of upper tract protection as well as a more refined technique of ureterointestinal anastomosis. Depending on the technique ureteroileal stenosis was lately reported to lie between 2.7 to 3.8%. Renal function remained stable in 96% after a mean follow-up of up to 5 years. Radical cystectomy in carefully selected patients has stood the test of time by providing adequate long-term survival and low local recurrence rates. Orthotopic bladder substitution does not compromise oncological outcome, yields excellent functional results, is cost effective compared to other types of urinary diversion, may improve quality of life and should therefore be the diversion of choice both in men and women. Chronological age is generally not a contraindication for cystectomy, but for orthotopic urinary diversion, tumor extent, functional pelvic floor deficits and general life expectancy are limiting factors.

  4. NF-κB诱骗剂——环状哑铃寡核苷酸抑制膀胱肿瘤细胞侵袭能力的研究%Experimental study on the invasiveness inhibition of bladder cancer cells by nuclear factor-κB decoy——circular dumbbell oligodeoxynucleotides

    Institute of Scientific and Technical Information of China (English)

    文博; 周四维; 杨为民

    2006-01-01

    Objective: To determine whether NF-κB is constitutively activated in human bladder cancer cell and, if so, to determine the invasiveness inhibition of bladder cancer cells by nuclear factor-κB decoy-circular dumbbell oligodeoxynucleotides (CD-ODN). Methods: NF-κBp65 activation was determined by immunohistochemical analysis of formalin-fixed, paraffin-embedded specimens from 38 cases of bladder transitional cell carcinoma patients. We quantified nuclear staining of RelA as a marker of NF-κBp65 activation. CD-ODN were transfected into human bladder cancer cell line BIU87 by lipofectamine. Luciferase reporter were applied to detecting NF-κB DNA binding activity. The expression levels of uPA were detected by RT-PCR and the cells' invasion ability by transwell cell culture chamber. Results: P65 excessive activation existed in tumor cell (P<0.01), the activation degree correlated significantly with the expression of uPA (r=0.89, P<0.01), as well as related to tumor invasion-related clinicopathological features such as lymphatic metastasis (P<0.01) and pathological ranking (P<0.05); After transfection with CD-ODN, the activation of NF-κB in BIU87 cell line was suppressed remarkably, the expression level of uPA was decreased and the cells' invasiveness was weakened as well. Conclusion: Excessively activated NF-κB is related to tumor progression possibly due to its transcriptional regulation of invasion-related factors such as uPA. CD-ODN can efficiently suppress DNA binding activity of NF-κB to reduce the invasive potency of tumor.

  5. Nonmuscle myosin II isoforms coassemble in living cells.

    Science.gov (United States)

    Beach, Jordan R; Shao, Lin; Remmert, Kirsten; Li, Dong; Betzig, Eric; Hammer, John A

    2014-05-19

    Nonmuscle myosin II (NM II) powers myriad developmental and cellular processes, including embryogenesis, cell migration, and cytokinesis [1]. To exert its functions, monomers of NM II assemble into bipolar filaments that produce a contractile force on the actin cytoskeleton. Mammalian cells express up to three isoforms of NM II (NM IIA, IIB, and IIC), each of which possesses distinct biophysical properties and supports unique as well as redundant cellular functions [2-8]. Despite previous efforts [9-13], it remains unclear whether NM II isoforms assemble in living cells to produce mixed (heterotypic) bipolar filaments or whether filaments consist entirely of a single isoform (homotypic). We addressed this question using fluorescently tagged versions of NM IIA, IIB, and IIC, isoform-specific immunostaining of the endogenous proteins, and two-color total internal reflection fluorescence structured-illumination microscopy, or TIRF-SIM, to visualize individual myosin II bipolar filaments inside cells. We show that NM II isoforms coassemble into heterotypic filaments in a variety of settings, including various types of stress fibers, individual filaments throughout the cell, and the contractile ring. We also show that the differential distribution of NM IIA and NM IIB typically seen in confocal micrographs of well-polarized cells is reflected in the composition of individual bipolar filaments. Interestingly, this differential distribution is less pronounced in freshly spread cells, arguing for the existence of a sorting mechanism acting over time. Together, our work argues that individual NM II isoforms are potentially performing both isoform-specific and isoform-redundant functions while coassembled with other NM II isoforms.

  6. Obscurins: Goliaths and Davids take over non-muscle tissues.

    Science.gov (United States)

    Ackermann, Maegen A; Shriver, Marey; Perry, Nicole A; Hu, Li-Yen R; Kontrogianni-Konstantopoulos, Aikaterini

    2014-01-01

    Obscurins comprise a family of proteins originally identified in striated muscles, where they play essential roles in myofibrillogenesis, cytoskeletal organization, and Ca(2+) homeostasis. They are encoded by the single OBSCN gene, and are composed of tandem adhesion domains and signaling motifs. To date, two giant obscurin isoforms have been described in detail that differ only at the extreme COOH-terminus; while obscurin-A (∼720 kDa) contains a non-modular COOH-terminus that harbors binding sites for the adaptor proteins ankyrins, obscurin-B (∼870 kDa) contains two COOH-terminal serine-threonine kinase domains preceded by adhesion motifs. Besides the two known giant obscurins, a thorough search of transcript databases suggests that complex alternative splicing of the obscurin transcript results in the generation of additional giant as well as small isoforms with molecular masses ranging between ∼50-970 kDa. These novel isoforms share common domains with the characterized isoforms, but also contain unique regions. Using a panel of highly specific antibodies directed against epitopes spanning the entire length of giant obscurins, we employed western blotting and immunohistochemistry to perform a systematic and comprehensive characterization of the expression profile of obscurins in muscle and non-muscle tissues. Our studies demonstrate for the first time that obscurins are not restricted to striated muscles, but are abundantly expressed in several tissues and organs including brain, skin, kidney, liver, spleen, and lung. While some obscurin isoforms are ubiquitously expressed, others are preferentially present in specific tissues and organs. Moreover, obscurins are present in select structures and cell types where they assume nuclear, cytosolic, and membrane distributions. Given the ubiquitous expression of some obscurins, along with the preferential expression of others, it becomes apparent that obscurins may play common and unique roles, respectively, in

  7. [Intradiverticular bladder tumors. Three case reports].

    Science.gov (United States)

    Fekak, H; Rabu, R; Joual, A; Bennani, S; Moufid, K; Sarf, S; Debragh, A; el Mimu, M; Benjelloun, S

    2002-01-01

    The bladder tumours in vesical diverticula is rare, and the poor prognosis, because it was often with early invasion. We reported three cases of bladder tumours in vesical diverticula, with delay of diagnosis two, eight and twelve months respectively. The radiology exploration suspected the diagnosis and the histology biopsy confirmed a diagnosis of primary transitional cell carcinoma in two cases: PTa GI and T2 GII, and in an other case it was a invasive epidermoid carcinoma. The first patient was dead by urethral resection of the bladder tumour. The second required a cytoprototectomy and the last patient. The treatment consisted of radiotherapy and chemotherapy. We insisted of the particularity diagnosis, histology and therapeutic for bladder tumour in vesical diverticula and the early diagnosis in order to have a good prognosis.

  8. Breast metastasis from carcinoma of gall bladder

    Directory of Open Access Journals (Sweden)

    Ajaz Ahmad Malik

    2013-01-01

    Full Text Available Carcinoma of gall bladder has early lymphatic and haematogenous spread. Most common extra abdominal site of metastasis is the lung. Metastasis to breast from carcinoma of breast is very rare. Our case describes an interesting case of carcinoma of gall bladder metastising to breast. A 50-year-old female presented to our outpatient department with a small nodule on upper outer quadrant of left breast. Patient had a history of cholecystectomy done for symptomatic gall stones 2 years back. Histopathological examination of the gall bladder specimen showed adenocarcinoma of the gall bladder with invasion to lamina propria. No additional treatment was offered to the patient. The breast nodule was excised and sent for histopathological examination. Histopathological examination revealed metastising adenocarcinoma. Patient was subjected to palliative chemotherapy (Gamcitabine and carboplatin. However, patient died of hepatic encephalopathy after 5 months. Our case reports an unusual site of metastasis from carcinoma of gall bladder which is very rare.

  9. NOTCH pathway inactivation promotes bladder cancer progression.

    Science.gov (United States)

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

    2015-02-01

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

  10. Molecular cystoscopy: Micro-RNAs could be a marker for identifying genotypic changes for transitional cell carcinoma of the urinary bladder

    Directory of Open Access Journals (Sweden)

    Nilay Mitash

    2016-01-01

    Full Text Available Introduction: Normal-looking mucosa may harbor genetic changes preceding a visible tumor. This study was aimed at exploring the role of the quantitative expression of micro-RNAs (miRNAs in bladder cancer tissue in comparison with normal mucosa and healthy controls (HCs as a molecular marker. Materials and Methods: Between October 2011 to December 2012, tissue from the bladder tumor of 21 patients (cases tumor, CT, normal mucosa (case control, CC of the same patients (n-21 and normal bladder mucosa from 10 HCs were obtained. miRNAs of angiogenesis, endothelial mesenchymal transition and apoptosis were quantified using stem-loop RT Taq Man polymerase chain reaction. Statistical analysis was performed using the Chi square and independent sample T tests by using SPSS version 16. Results: The mean age of the patients and controls were 55.41 ± 11.03 and 52.14 ± 13.04 years. miR-21, miR-205, miR-126, miR-10b and miR-200a were highly expressed in CT (P < 0.027, <0.048, <0.025, <0.029 and < 0.005 as compared with HC. Expression of miR-21 and miR-129 were both correlated with grade and stage (P = 0.001 and < 0.009, respectively and the level of expression was different in the same grade of non-muscle invasive tumors. The fold change of miR129, miR205 and miR200a was significantly higher in the normal-looking mucosa of bladder tumor patients than the HC (P < 0.005. Conclusion: Expression of miR129, miR205 and miR200a in the normal-looking mucosa of bladder cancer patients was significantly higher than the normal mucosa of a HC. This may help in predicting recurrence and formulating the follow-up strategy.

  11. 吉西他滨与顺铂新辅助化疗治疗肌层浸润性膀胱癌疗效观察%Effectiveness of neoadjuvent chemotherapy with gemcitabine and cisplatin for muscle invasive bladder carcinoma

    Institute of Scientific and Technical Information of China (English)

    张鑫; 肖博; 陈松; 胡卫国; 李建兴

    2015-01-01

    Objective To investigate the effectiveness of gemcitabine and cisplatin as neoadjuvent chemotherapy for muscle-invasive bladder cancer.Methods Seventy-four cases of muscle invasive bladder cancer,staging T3-T4a were recruited.Thirty-four cases received radical cystectomy (RC).The rest 40 cases who were not willing to receive RC received 2 cycles of gemcitabine and cisplatin neoadjuvent chemotherapy followed by cystoscopy biopsy:11 cases were stable or with progression,who received RC:24 cases lowered to T0-T1,and they received 3 cycles of gemcitabine and cisplatin systemic chemotherapy again and then received trans-urethra resection of bladder tumor;cases lowered to T2-T3,and received RC.Tumor specific survival rate,overall survival rate,as well as bladder preservation rate of different groups was compared.Results In gemcitabine + cisplatin group,overall response rate was 51.6%,and complete reaction rate was 26.3%.Three-year overall survival rate in gemcitabine + cisplatin group was 49.7%,and 49.3% in control group (P > 0.05).Three-year progression-free survival in gemcitabine + cisplatin group was 34.9%,and that in control group was 41.1% (P > 0.05).The bladder in 24.2% of the patients in gemcitabine + cisplatin group was preserved.Overall survival rate in patients with response was 76.0%,and 100.0% in complete response patients.Conclusion During a follow-up period of 3 years,the oservall suvival and progression-free survival were not increased by gemcitabine and cisplatin neoadjuvent chemotherapy for muscle invasive bladder carcinoma in comparison to the RC,but the bladder in relative proportion of patients is preserved.%目的 探讨吉西他滨与顺铂新辅助化疗治疗肌层浸润性膀胱癌的疗效.方法 我院74例肌层浸润性膀胱癌T3 ~T4a期患者,其中34例患者直接行膀胱全切术,其余40例不愿直接行膀胱全切的患者接受2个周期的髂内动脉吉西他滨与顺铂新辅助

  12. Preoperative lymph-node staging of invasive urothelial bladder cancer with 18F-fluorodeoxyglucose positron emission tomography/computed axial tomography and magnetic resonance imaging

    DEFF Research Database (Denmark)

    Jensen, Thor Knak; Holt, Per; Gerke, Oke

    2011-01-01

    investigated the value of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed axial tomography (¹⁸F-FDG PET/CT) and magnetic resonance imaging (MRI) for preoperative N staging of bladder cancer. Material and methods. From June 2006 to January 2008, 48 consecutive patients diagnosed with bladder...... cancer were referred to preoperative staging including MRI and ¹⁸F-FDG PET/CT. Eighteen out of 48 patients underwent radical cystoprostatectomy including removal of lymph nodes for histology, and were included in the study. Values of ¹⁸F-FDG PET/CT and MRI for regional N staging were compared...... to histopathology findings, the gold standard. Results. ¹⁸F-FDG PET/CT and MRI were performed in 18 patients. The specificities for detection of lymph-node metastases for MRI and ¹⁸F-FDG PET/CT were 80% (n = 15) and 93.33% (n = 15), respectively. The negative predictive values were 80% (n = 15) and 87.5% (n = 16...

  13. Bladder Cancer Advocacy Network

    Science.gov (United States)

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

  14. Prostate resection - minimally invasive

    Science.gov (United States)

    ... invasive URL of this page: //medlineplus.gov/ency/article/007415.htm Prostate resection - minimally invasive To use ... into your bladder instead of out through the urethra ( retrograde ... on New Developments in Prostate Cancer and Prostate Diseases. Evaluation and treatment of lower ...

  15. MiR-126 regulates proliferation and invasion in the bladder cancer BLS cell line by targeting the PIK3R2-mediated PI3K/Akt signaling pathway

    Directory of Open Access Journals (Sweden)

    Xiao J

    2016-08-01

    Full Text Available Jun Xiao,1 Huan-Yi Lin,2 Yuan-Yuan Zhu,3 Yu-Ping Zhu,1 Ling-Wu Chen2 1Department of Urology, Anhui Provincial Hospital, Anhui Medical University, Hefei, 2Department of Urology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 3Clinical Laboratory, Anhui Provincial Hospital, Anhui Medical University, Hefei, People’s Republic of China Objective: To assess whether microRNA-126 (miR-126 targets phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2 and to determine the potential roles of miR-126 in regulating proliferation and invasion via the PIK3R2-mediated phosphatidylinositol 3 kinase (PI3K-protein kinase B (Akt signaling pathway in the human bladder BLS cell line. Materials and methods: A recombinant lentivirus (Lv vector expressing miR-216 (Lv-miR-126 was successfully constructed, and Lv-miR-126 and Lv vector were transfected into the BLS cell line. A direct regulatory relationship between miR-126 and the PIK3R2 gene was demonstrated by luciferase reporter assays. To determine whether PIK3R2 directly participates in the miR-126-induced effects in BLS cells, anti-miR-126 and a PIK3R2 small interfering RNA (siRNA were transfected into the BLS cells. Quantitative real-time polymerase chain reaction was used to measure miR-126 and PIK3R2 expressions. 5-Ethynyl-2'-deoxyuridine and colony formation assays to assess cell proliferation, flow cytometry for cell apoptosis and cell cycle analysis, Transwell assays for cell migration and invasion, and Western blots for PIK3R2, PI3K, phosphorylated PI3K (p-PI3K, Akt, and phosphorylated Akt (p-Akt protein expressions were performed. Results: Lv-miR-126 significantly enhanced the relative expression of miR-126 in the BLS cells after infection (P<0.0001. MiR-126 overexpression inhibited the proliferation, cloning, migration, and invasion of BLS cells, promoted cell apoptosis, and induced S phase arrest (all P<0.05. PIK3R2, p-PI3K, and p-Akt protein expressions were significantly

  16. The response of variant histology bladder cancer to intravesical immunotherapy compared to conventional cancer

    Directory of Open Access Journals (Sweden)

    Ofer Nathan Gofrit

    2016-03-01

    Full Text Available Background: High-grade urothelial carcinomas (UC often show foci of variant differentiation. There is limited information in the literature about the response of these variant urothelial tumors to immunotherapy with Bacillus Calmette Guerin (BCG. We compared the response to treatment with BCG of UC containing glandular, squamous, nested and micropapillary types of differentiation to response of conventional non-muscle invasive high-grade urothelial carcinoma. Methods: A total of 100 patients were diagnosed with variant histology urothelial cancer between June 1995 and December 2013. 41 patients with Ta or T1, confirmed by 2nd look biopsies, received immunotherapy with BCG. Fourteen patients in this group were diagnosed with micropapillary differentiation 13 patients with squamous differentiation, in 9 patients glandular differentiation was seen and in 7 patients nested variant. The control group included 140 patients with conventional high-grade UC. Both groups have been treated and followed similarly. Findings: Patients with variant tumors had similar clinical features to patients with conventional disease including: age, males to female ratio, stage, presence of Tis and median follow-up. Patients with variant tumors had a significantly worse prognosis compared to patients with conventional high-grade UC including: 5-year recurrence-free survival (63.5% Vs. 71.5%, p=0.05, 5-year progression to≥T2 -free survival (60% Vs. 82.5%, p=0.002, 5-year disease-specific survival (73% Vs. 92.5%, p=0.0004 and overall survival (66% Vs. 89.5%, 0.05. Interpretation: A patient with variant bladder cancer treated with intra-vesical immunotherapy has a 27% chance of dying from this disease within 5-years compared to 7.5% for a patient with conventional high-grade UC.

  17. HSPA6 augments garlic extract-induced inhibition of proliferation, migration, and invasion of bladder cancer EJ cells; Implication for cell cycle dysregulation, signaling pathway alteration, and transcription factor-associated MMP-9 regulation

    Science.gov (United States)

    Hwang, Byungdoo; Noh, Dae-Hwa; Park, Sung Lyea; Kim, Won Tae; Park, Sung-Soo; Kim, Wun-Jae; Moon, Sung-Kwon

    2017-01-01

    Although recent studies have demonstrated the anti-tumor effects of garlic extract (GE), the exact molecular mechanism is still unclear. In this study, we investigated the molecular mechanism associated with the inhibitory action of GE against bladder cancer EJ cell responses. Treatment with GE significantly inhibited proliferation of EJ cells dose-dependently through G2/M-phase cell cycle arrest. This G2/M-phase cell cycle arrest by GE was due to the activation of ATM and CHK2, which appears to inhibit phosphorylation of Cdc25C (Ser216) and Cdc2 (Thr14/Tyr15), this in turn was accompanied by down-regulation of cyclin B1 and up-regulation of p21WAF1. Furthermore, GE treatment was also found to induce phosphorylation of MAPK (ERK1/2, p38MAPK, and JNK) and AKT. In addition, GE impeded the migration and invasion of EJ cells via inhibition of MMP-9 expression followed by decreased binding activities of AP-1, Sp-1, and NF-κB motifs. Based on microarray datasets, we selected Heat shock protein A6 (HSPA6) as the most up-regulated gene responsible for the inhibitory effects of GE. Interestingly, overexpression of HSPA6 gene resulted in an augmentation effect with GE inhibiting proliferation, migration, and invasion of EJ cells. The augmentation effect of HSPA6 was verified by enhancing the induction of G2/M-phase-mediated ATM-CHK2-Cdc25C-p21WAF1-Cdc2 cascade, phosphorylation of MAPK and AKT signaling, and suppression of transcription factor-associated MMP-9 regulation in response to GE in EJ cells. Overall, our novel results indicate that HSPA6 reinforces the GE-mediated inhibitory effects of proliferation, migration, and invasion of EJ cells and may provide a new approach for therapeutic treatment of malignancies. PMID:28187175

  18. Prospective Study Delivering Simultaneous Integrated High-dose Tumor Boost (≤70 Gy) With Image Guided Adaptive Radiation Therapy for Radical Treatment of Localized Muscle-Invasive Bladder Cancer.

    Science.gov (United States)

    Hafeez, Shaista; Warren-Oseni, Karole; McNair, Helen A; Hansen, Vibeke N; Jones, Kelly; Tan, Melissa; Khan, Attia; Harris, Victoria; McDonald, Fiona; Lalondrelle, Susan; Mohammed, Kabir; Thomas, Karen; Thompson, Alan; Kumar, Pardeep; Dearnaley, David; Horwich, Alan; Huddart, Robert

    2016-04-01

    Image guided adaptive radiation therapy offers individualized solutions to improve target coverage and reduce normal tissue irradiation, allowing the opportunity to increase the radiation tumor dose and spare normal bladder tissue. A library of 3 intensity modulated radiation therapy plans were created (small, medium, and large) from planning computed tomography (CT) scans performed at 30 and 60 minutes; treating the whole bladder to 52 Gy and the tumor to 70 Gy in 32 fractions. A "plan of the day" approach was used for treatment delivery. A post-treatment cone beam CT (CBCT) scan was acquired weekly to assess intrafraction filling and coverage. A total of 18 patients completed treatment to 70 Gy. The plan and treatment for 1 patient was to 68 Gy. Also, 1 patient's plan was to 70 Gy but the patient was treated to a total dose of 65.6 Gy because dose-limiting toxicity occurred before dose escalation. A total of 734 CBCT scans were evaluated. Small, medium, and large plans were used in 36%, 48%, and 16% of cases, respectively. The mean ± standard deviation rate of intrafraction filling at the start of treatment (ie, week 1) was 4.0 ± 4.8 mL/min (range 0.1-19.4) and at end of radiation therapy (ie, week 5 or 6) was 1.1 ± 1.6 mL/min (range 0.01-7.5; P=.002). The mean D98 (dose received by 98% volume) of the tumor boost and bladder as assessed on the post-treatment CBCT scan was 97.07% ± 2.10% (range 89.0%-104%) and 99.97% ± 2.62% (range 96.4%-112.0%). At a median follow-up period of 19 months (range 4-33), no muscle-invasive recurrences had developed. Two patients experienced late toxicity (both grade 3 cystitis) at 5.3 months (now resolved) and 18 months after radiation therapy. Image guided adaptive radiation therapy using intensity modulated radiation therapy to deliver a simultaneous integrated tumor boost to 70 Gy is feasible, with acceptable toxicity, and will be evaluated in a randomized trial. Copyright © 2016 The Authors. Published by Elsevier Inc. All

  19. Research on the effects of piperine on proliferation and invasion of human bladder cancer T24 ;Cells%胡椒碱对人膀胱癌 T24细胞增殖及侵袭作用的研究

    Institute of Scientific and Technical Information of China (English)

    周俊杰

    2015-01-01

    目的:探讨不同浓度胡椒碱对膀胱癌 T24细胞增殖和侵袭作用的影响。方法用不同浓度的胡椒碱(5、10、20、40、80、160μmol/L)处理体外培养的膀胱癌 T24细胞,然后通过 MTT实验、Transwell 实验、Western blot 等方法检测 bax 和 bcl-2的表达以及 T24细胞的增殖和凋亡情况。结果胡椒碱作用于 T24细胞24 h 后,IC50值为38.73μmol/L,并且呈剂量依赖性。随着胡椒碱浓度的增加,T24细胞活性被抑制作用明显增加,且抑凋亡蛋白 bcl-2的表达量减少,促凋亡蛋白 bax 的表达量增加。结论胡椒碱对膀胱癌 T24细胞具有抑制增殖及促进其凋亡的作用。%Objective To investigate the effects of differentpiperine concentrationson the prolif-eration and invasion of bladder cancer T24 cells.Methods Bladder cancer T24 cells were treated with different concentrations of piperine(5,1 0,20,40,80,and 1 60μmol/L).Then MTT assay,Transwell exper-iments,and western blot were used to detect the expression of bax and bcl-2,and the proliferation and ap-optosis of T24 cells.Results After a 24-hour treatment of piperine,IC50 value was 38.73μmol/L.With the increaseof piperine concentrations,the activity of T24 cell was significantly inhibited in a dose-depend-ent manner.Westernblot showed that the expression of anti-apoptotic protein bcl-2 reduced,and the pro-apoptotic protein bax increased.Conclusion Piperine could inhibit the proliferation of bladder cancer T24 cells and promote the apoptosis of T24 cells.

  20. Neurogenic bladder in spinal cord injury patients

    Directory of Open Access Journals (Sweden)

    Al Taweel W

    2015-06-01

    Full Text Available Waleed Al Taweel, Raouf SeyamDepartment of Urology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaAbstract: Neurogenic bladder dysfunction due to spinal cord injury poses a significant threat to the well-being of patients. Incontinence, renal impairment, urinary tract infection, stones, and poor quality of life are some complications of this condition. The majority of patients will require management to ensure low pressure reservoir function of the bladder, complete emptying, and dryness. Management typically begins with anticholinergic medications and clean intermittent catheterization. Patients who fail this treatment because of inefficacy or intolerability are candidates for a spectrum of more invasive procedures. Endoscopic managements to relieve the bladder outlet resistance include sphincterotomy, botulinum toxin injection, and stent insertion. In contrast, patients with incompetent sphincters are candidates for transobturator tape insertion, sling surgery, or artificial sphincter implantation. Coordinated bladder emptying is possible with neuromodulation in selected patients. Bladder augmentation, usually with an intestinal segment, and urinary diversion are the last resort. Tissue engineering is promising in experimental settings; however, its role in clinical bladder management is still evolving. In this review, we summarize the current literature pertaining to the pathology and management of neurogenic bladder dysfunction in patients with spinal cord injury.Keywords: neurogenic bladder, spinal cord injury, urodynamics, intestine, intermittent catheterization

  1. 水通道蛋白1、3在非肌层浸润性膀胱癌组织中的表达及其与复发现象的相关性%Expression and correlation with recurrence of 1, 3 aquaporins in non-muscle invasive bladder cancer

    Institute of Scientific and Technical Information of China (English)

    拜合提亚·阿扎提; 王文光; 范兆阳; 木拉提·热夏提; 阿不都许库尔·阿不力米提; 王玉杰

    2012-01-01

    目的 研究水通道蛋白1、3 (AQP1、AQP3)在非肌层浸润性膀胱癌组织中的表达及其与膀胱癌复发现象的相关性.方法 采用免疫组织化学S-P法、Wester blot 蛋白免疫印迹法检测15例经尿道膀胱癌电切术后非肌层浸润性膀胱癌组织及15例复发组织水通道蛋白1、3的表达量,分析两者在复发前及复发前后表达量的差异与复发时间的相关性.结果 复发后水通道蛋白1、3的表达量较复发前有所增加,且复发前蛋白表达量高的容易复发,其蛋白表达增加的量与随访的复发时间之间呈负相关.结论 水通道蛋白1、3的表达量在复发后的明显增加,其增加的量及初发后蛋白表达量与随访的复发时间相关,AQP1、AQP3可成为检测膀胱癌早期复发的有效指标之一.

  2. What Is Bladder Cancer?

    Science.gov (United States)

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

  3. Treatment of non muscle invasive bladder tumor related to the problem of bacillus Calmette-Guerin availability. Consensus of a Spanish expert's panel. Spanish Association of Urology.

    Science.gov (United States)

    Fernández-Gómez, J M; Carballido-Rodríguez, J; Cozar-Olmo, J M; Palou-Redorta, J; Solsona-Narbón, E; Unda-Urzaiz, J M

    2013-01-01

    Since June 2012, the has been a worldwide lack of available of the Connaught strain. In December 2012, a group of experts met in the Spanish Association of Urology to analyze this situation and propose alternatives. To present the work performed by said committee and the resulting recommendations. An update has been made of the principal existing evidence in the treatment of middle and high risk tumors. Special mention has been made regarding the those related with the use of BCG and their possible alternative due to the different availability of BCG. In tumors with high risk of progression, immediate cystectomy should be considered when BCG is not available, with dose reduction or alternating with chemotherapy as methods to economize on the use of BCG when availability is reduced. In tumors having middle risk of progression, chemotherapy can be used, although when it is associated to a high risk of relapse, BCG would be indicated if available with the mentioned savings guidelines. BCG requires maintenance to maintain its effectiveness, it being necessary to optimize the application of endovesical chemotherapy and to use systems that increase its penetration into the bladder wall (EMDA) if they are available. Due to the scarcity of BCG, it has been necessary to agree on a series of recommendations that have been published on the web page of the Spanish Association of Urology. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  4. Prognosis analysis of radical cystectomy in patients with muscle-invasive bladder cancer%肌层浸润性膀胱癌患者根治性膀胱切除术的预后分析

    Institute of Scientific and Technical Information of China (English)

    牛吉瑞; 王海; 范欣荣; 纪志刚

    2015-01-01

    Objective To explore the prognosis factors of radical cystectomy in patients with muscleinvasive bladder cancer factors of radical bladder cystectomy.Methods Clinical data of 36 cases with muscleinvasive bladder cancer after radical cystectomy from January 2008 to June 2011 were selected.Kapplan-Meier method and Cox regression model were used to analyze the prognosis factors including sex,age,hematuria,clinical staging,neoadjavant chemotherapy,tumor number,tumor size,Kamofsky scores 3 months after operation,alkaline phosphatase,lactic dehydrogenase and hemoglobin..Results The 1 year and 3 years survival rates were 86.1% (31/36) and 75% (27/36),respectively.Kaplan-Meier method showed that preoperative neoadjavant chemotherapy and postoperative Karnofsky scores were the influencing factors of prognosis (x2 =8.532,P =0.003 ; x2 =5.482,P =0.003).Cox regression model showed that preoperative neoadjuvant chemotherapy was the independent factor of prognosis (P =0.037,RR =0.107,95% CI:0.013-0.873).Conclusion There is a correlation between prognosis of radical cystectomy and preoperative neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer; preoperative neoajuvant chemotherapy is the protective factor.%目的 探讨肌层浸润性膀胱癌患者根治性膀胱切除术的预后影响因素.方法 选择北京协和医院2008年1月至201 1年6月所收治的肌层浸润性尿路上皮细胞癌患者36例,采用Kaplan-Meier法以及Cox比例回归风险模型对预后影响因素包括患者的性别、年龄、TNM临床分期、术前是否行新辅助化疗、肿瘤数目、肿瘤大小、术后3个月卡氏评分、碱性磷酸酶、乳酸脱氢酶、血红蛋白等因素进行分析.结果 36例患者1年生存率为86.1% (31/36),3年生存率为75.0% (27/36).单因素分析发现,术前行新辅助化疗和术后卡氏评分是对根治性膀胱切除术预后有影响的因素(x2=8.532,P=0.003;x2=5.482,P=0.003).Cox比例回归风险模型

  5. Conditional deletion of nonmuscle myosin II-A in mouse tongue epithelium results in squamous cell carcinoma.

    Science.gov (United States)

    Conti, Mary Anne; Saleh, Anthony D; Brinster, Lauren R; Cheng, Hui; Chen, Zhong; Cornelius, Shaleeka; Liu, Chengyu; Ma, Xuefei; Van Waes, Carter; Adelstein, Robert S

    2015-09-15

    To investigate the contribution of nonmuscle myosin II-A (NM II-A) to early cardiac development we crossed Myh9 floxed mice and Nkx2.5 cre-recombinase mice. Nkx2.5 is expressed in the early heart (E7.5) and later in the tongue epithelium. Mice homozygous for deletion of NM II-A (A(Nkx)/A(Nkx)) are born at the expected ratio with normal hearts, but consistently develop an invasive squamous cell carcinoma (SCC) of the tongue (32/32 A(Nkx)/A(Nkx)) as early as E17.5. To assess reproducibility a second, independent line of Myh9 floxed mice derived from a different embryonic stem cell clone was tested. This second line also develops SCC indistinguishable from the first (15/15). In A(Nkx)/A(Nkx) mouse tongue epithelium, genetic deletion of NM II-A does not affect stabilization of TP53, unlike a previous report for SCC. We attribute the consistent, early formation of SCC with high penetrance to the role of NM II in maintaining mitotic stability during karyokinesis.

  6. Effectiveness of transurethral resection under the control of photodynamic diagnosis and intravesical instillation of bacillus Calmette–Guérin in case of poorly differentiated non-muscle-invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    A. I. Rolevich

    2016-01-01

    Full Text Available Background. High-grade non-muscle-invasive bladder cancer (NMIBC is characterized by a high rate of recurrence, progression, and mortality associated with this disease. Organ-preserving treatment by transurethral resection and immunotherapy with bacillus Calmette-Guerin (BCG is an initial approach to therapy in these patients. However, the efficacy of such therapy is limited. This justifies the use of other methods of treatment, such as TUR under the control of photodynamic diagnosis (PDD. Aim of this study was to evaluate the effectiveness of therapeutic interventions in patients with high-grade NMIBC.Materials and methods. We have retrospectively analyzed results of follow-up of patients with primary or recurrent high-grade transitional cell NMIBC, treatment by TUR in conjunction with BCG or without it N.N. Alexandrov National Cancer Centre in the period from 2004 to 2013. In total, the study included 113 patients (27 women and 86 men, in the median age of 72 years. We have evaluated 5-year recurrence- and progression-free survival, analyzed an influence of prognostic factors and methods of treatment on the risk of recurrence and progression with Cox model and Kaplan–Meier method.Results. With a median of follow up of 59 (12–116 months the rates of 5-year recurrence- and progression-free survival were respectively 42.5 and 71.6 %. Statistically significant association with the risk of recurrence was observed in multivariate Cox regression analysis for recurrent tumors (hazard ratio (HR 2.73; 95 % confidence interval (CI 1.61–4.62 and immunotherapy with BCG (HR 0.56; 95 % CI 0.31–0.99. BCG significantly increased recurrence-free survival in patients with both primary tumors, and with recurrent ones. Significant factors in the multivariate analysis with regard to the risk of progression were suspicion for muscle-invasive tumors according to the cystoscopic picture (HR 3.36; 95 % CI 1.09–10.4, abnormal tumor-free bladder mucosa

  7. Establishment and antitumor effects of dasatinib and PKI-587 in BD-138T, a patient-derived muscle invasive bladder cancer preclinical platform with concomitant EGFR amplification and PTEN deletion

    Science.gov (United States)

    Lim, Joung Eun; Jeong, Da Eun; Song, Hye Jin; Kim, Sudong; Nam, Do-Hyun; Sung, Hyun Hwan; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han-Yong; Jeon, Hwang Gyun

    2016-01-01

    Muscle-invasive bladder cancer (MIBC) consists of a heterogeneous group of tumors with a high rate of metastasis and mortality. To facilitate the in-depth investigation and validation of tailored strategies for MIBC treatment, we have developed an integrated approach using advanced high-throughput drug screening and a clinically relevant patient-derived preclinical platform. We isolated patient-derived tumor cells (PDCs) from a rare MIBC case (BD-138T) that harbors concomitant epidermal growth factor receptor (EGFR) amplification and phosphatase and tensin homolog (PTEN) deletion. High-throughput in vitro drug screening demonstrated that dasatinib, a SRC inhibitor, and PKI-587, a dual PI3K/mTOR inhibitor, exhibited targeted anti-proliferative and pro-apoptotic effects against BD-138T PDCs. Using established patient-derived xenograft models that successfully retain the genomic and molecular characteristics of the parental tumor, we confirmed that these anti-tumor responses occurred through the inhibition of SRC and PI3K/AKT/mTOR signaling pathways. Taken together, these experimental results demonstrate that dasatinib and PKI-587 might serve as promising anticancer drug candidates for treating MIBC with combined EGFR gene amplification and PTEN deletion. PMID:27438149

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

    Science.gov (United States)

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

    2000-11-01

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

  9. Clostridium perfringens enterotoxin as a potential drug for intravesical treatment of bladder cancer.

    Science.gov (United States)

    Gabig, Theodore G; Waltzer, Wayne C; Whyard, Terry; Romanov, Victor

    2016-09-16

    The current intravesical treatment of bladder cancer (BC) is limited to a few chemotherapeutics that show imperfect effectiveness and are associated with some serious complications. Thus, there is an urgent need for alternative therapies, especially for patients with high-risk non-muscle invasive (NMIBC). Clostridium perfringens enterotoxin (CPE), cytolytic protein binds to its receptors: claudin 3 and 4 that are expressed in epithelial cells. This binding is followed by rapid cell death. Claudin 4 is present in several epithelial tissue including bladder urothelium and its expression is elevated in some forms of BC. In addition to directly targeting BC cells, binding of CPE to claudins increases urothelium permeability that creates conditions for better accession of the tumor. Therefore, we evaluated CPE as a candidate for intravesical treatment of BC using a cellular model. We examined cytotoxicity of CPE against BC cells lines and 3D cultures of cells derived from surgical samples. To better elucidate cellular mechanisms, activated by CPE and to consider the use of CPE non-toxic fragment (C-CPE) for combination treatment with other drugs we synthesized C-CPE, compared its cytotoxic activity with CPE and examined claudin 4 expression and intracellular localization after C-CPE treatment. CPE induced cell death after 1 h in low aggressive RT4 cells, in moderately aggressive 5637 cells and in the primary 3D cultures of BC cells derived from NMIBC. Conversely, non-transformed urothelial cells and cells derived from highly aggressive tumor (T24) survived this treatment. The reason for this resistance to CPE might be the lower expression of CLDNs or their inaccessibility for CPE in these cells. C-CPE treatment for 48 h did not affect cell viability in tested cells, but declined expression of CLDN4 in RT4 cells. C-CPE increased sensitivity of RT4 cells to Mitommycin C and Dasatinib. To better understand mechanisms of this effect we examined expression and

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

    Science.gov (United States)

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

    2015-05-01

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

  11. 吉西他滨联合卡铂治疗浸润性膀胱癌手术患者临床研究%Clinical Research of Gemcitabine Combined with Carboplatin in Treating Patients with Invasive Bladder Cancer Surgery

    Institute of Scientific and Technical Information of China (English)

    刘春林; 渠渊; 张进生; 柴军; 刘宁; 吴宗山

    2016-01-01

    Objective To observe the clinical efficacy of gemcitabine and carboplatin used in the chemotherapy before the invasive bladder cancer surgery. Methods 100 patients with invasive bladder cancer patients who met the inclusion criteria were randomly divided into the study group and the control group,50 cases in each group. The study group received gemcitabine+carboplatin,the control group re-ceived gemcitabine+cisplatin,21 d was 1 course of treatment. The recent adverse reactions were evaluated in the two groups after com-pleting 2-3 cycles of chemotherapy;after chemotherapy,all patients were treated with surgery that retained the bladder,and the long-term prognosis were observed and compared between the two groups. Results The response rate of the study group was 79. 59%,the total effective rate was 95. 92%,which had no statistically significant difference with 68. 75%,91. 67% of the control group( P > 0. 05);the tumor sizes of the two groups after chemotherapy were significantly reduced compared with before chemotherapy ( P 0. 05);the 3-year median survival time of the study group was 24. 5 months,which was longer than 23. 7 months of the control group but without statistically significant difference(χ2= 0. 846,P > 0. 05). Conclusion Preoperative gemcitabine combined with carboplatin in chemotherapy before invasive bladder cancer surgery has equivalent effect with gemcitabine combined with cisplatin,but the former combination has fewer in-cidence of adverse reactions,especially lower incidence of renal damage.%目的:观察吉西他滨联合卡铂在浸润性膀胱癌手术前化学治疗(简称化疗)中的临床疗效。方法将100例浸润性膀胱癌患者按随机数字表法分为研究组和对照组,各50例。研究组患者采用吉西他滨+卡铂方案,对照组患者采用吉西他滨+顺铂方案,21 d为1个化疗周期。两组患者均在完成2~3个周期后对化疗的近期疗效及不良反应进行评价;化疗后均采用保留

  12. Hedgehog pathway activation in human transitional cell carcinoma of the bladder

    OpenAIRE

    2012-01-01

    Background: The Hedgehog (Hh) signalling pathway functions as an organiser in embryonic development. Recent studies have shown constitutive activation of this pathway in various malignancies, but its role in bladder cancer remains poorly studied. Methods: Expression levels of 31 genes and 9 microRNAs (miRNAs) involved in the Hh pathway were determined by quantitative real-time RT–PCR in 71 bladder tumour samples (21 muscle-invasive (MIBC) and 50 non-muscle-invasive (NMIBC) bladder cancers), a...

  13. Radical radiotherapy for urinary bladder cancer

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  14. Oncolytic Viruses in the Treatment of Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Kyle G. Potts

    2012-01-01

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

  15. Overactive bladder in children

    Science.gov (United States)

    Ramsay, Sophie; Bolduc, Stéphane

    2017-01-01

    Overactive bladder (OAB) is a highly prevalent disorder in the pediatric population. This condition is especially troublesome for pediatric patients and their families when associated with incontinence, since it negatively affects self-esteem and impairs children’s development. From the patient’s perspective, urgency and urge incontinence can have a significant impact, negatively affecting their quality of life. For a therapy to have true benefit, changes must not only be statistically significant, but must also be perceived as meaningful by the patient. A stepwise approach is favoured to treat this pathology, starting with behavioural therapy, followed by medical management, and eventually more invasive procedures. Antimuscarinic agents are the mainstay of medical treatment for OAB. Oxybutynin is the most commonly used antimuscarinic in the pediatric population. However, some patients have a suboptimal response to antimuscarinics and many experience bothersome side effects, which have been documented with all antimuscarinics to a significantly higher degree than placebo. Although there have been reports about the use of tolterodine, fesoterodine, trospium, propiverine, and solifenacin in children, to date, only oxybutynin has been officially approved for pediatric use by medical authorities in North America. This review will address alternative treatment options for pediatric patients presenting with OAB, from conservative measures to more invasive therapies. PMID:28265325

  16. Nonmuscle Myosin II helps regulate synaptic vesicle mobility at the Drosophila neuromuscular junction

    OpenAIRE

    Qiu Xinping; Seabrooke Sara; Stewart Bryan A

    2010-01-01

    Abstract Background Although the mechanistic details of the vesicle transport process from the cell body to the nerve terminal are well described, the mechanisms underlying vesicle traffic within nerve terminal boutons is relatively unknown. The actin cytoskeleton has been implicated but exactly how actin or actin-binding proteins participate in vesicle movement is not clear. Results In the present study we have identified Nonmuscle Myosin II as a candidate molecule important for synaptic ves...

  17. H2AX phosphorylation level in peripheral blood mononuclear cells as an event-free survival predictor for bladder cancer.

    Science.gov (United States)

    Turinetto, Valentina; Pardini, Barbara; Allione, Alessandra; Fiorito, Giovanni; Viberti, Clara; Guarrera, Simonetta; Russo, Alessia; Anglesio, Silvia; Ruo Redda, Maria Grazia; Casetta, Giovanni; Cucchiarale, Giuseppina; Destefanis, Paolo; Oderda, Marco; Gontero, Paolo; Rolle, Luigi; Frea, Bruno; Vineis, Paolo; Sacerdote, Carlotta; Giachino, Claudia; Matullo, Giuseppe

    2016-11-01

    Bladder cancer (BC) has a typical aetiology characterized by a multistep carcinogenesis due to environmental exposures, genetic susceptibility, and their interaction. Several lines of evidence suggest that DNA repair plays a role in the development and progression of BC. In particular, the study of individual susceptibility to DNA double strand breaks (DSBs) may provide valuable information on BC risk, and help to identify those patients at high-risk of either recurrence or progression of the disease, possibly personalizing both surveillance and treatment. Among the different DSB markers, the most well characterized is phosphorylation of the histone H2AX (γ-H2AX). We assessed any potential role of γ-H2AX as a molecular biomarker in a case-control study (146 cases and 146 controls) to identify individuals with increased BC risk and at high-risk of disease recurrence or progression. We investigated γ-H2AX levels in peripheral blood mononuclear cells before and after their exposure to ionizing radiation (IR). We did not find any significant difference among cases and controls. However, we observed a significant association between γ-H2AX basal levels and risk of disease recurrence or progression. In particular, both BC patients as a whole and the subgroup of non-muscle invasive BC (NMIBC) with high basal H2AX phosphorylation levels had a decreased risk of recurrence or progression (for all BC HR 0.70, 95%CI 0.52-0.94, P = 0.02; for NMIBC HR 0.68, 95%CI 0.50-0.92, P = 0.01), suggesting a protective effect of basal DSB signaling. Our data suggest that γ-H2AX can be considered as a potential molecular biomarker to identify patients with a higher risk of BC recurrence. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  18. The paediatric neuropathic bladder

    African Journals Online (AJOL)

    spinal reflex arc that occurs when the bladder becomes autonomous from higher ... rise in the pressure v. time trace with bladder filling, representing a typical poorly .... reactions. Furthermore, new-generation anticholinergic agents, such.

  19. Transurethral en bloc resection of bladder tumors

    Directory of Open Access Journals (Sweden)

    A. G. Martov

    2015-01-01

    Full Text Available Background. The high incidence of recurrent non-muscle-invasive bladder carcinoma (BC necessitates searches for new surgical methods. Objective: to comparatively evaluate the efficiency and safety of en block resection of bladder tumors versus transurethral resection (TUR. Subjects and methods. In January 2010 to June 2013, a total of 292 patients with primary and recurrent bladder tumor stages, cTa-T2, underwent transurethral endoscopic treatment (as TUR at the Unit of Minimally Invasive Urology, Moscow City Clinical Hospital Fifty-Seven. A major portion of these patients were included in the study of the efficiency and safety of en bloc TUR of bladder tumors. The criteria for study inclusion were primary or recurrent non-muscle-invasive bladder tumor measuring 1 to 3 cm, stage pTa-T1, signed informed consent to participate in the study and patients» readiness to undergo control examinations in inpatient setting for one year. The exclusion criteria were a confirmed or detected muscleinvasive tumor, multiple bladder involvement (> 3 tumors, as well as detected tumors spreading to the ureter, bladder neck, and prostatic urethra. The primary study endpoint was considered to be a recurrence of a tumor after TUR of the bladder (TURB. The secondary endpoint was the frequency of concealed bladder perforation, blood transfusions, recystoscopies for bladder tamponade, early recystoscopies to specify a BC stage, and the frequency of immediate intravesical injection of a chemical. For final analysis, the investigators selected 106 patients in a group where tumors were removed en bloc (a study group and 133 patients in a group where tumors were retrieved using traditional TURB (a control group. In the study group, the tumor was removed en bloc by a monopolar J-shaped electrode (sand wedge electrode in 45 patients, by a hook-like electrode in 14, by a hybrid procedure (hydropreparation and monopolar electrosurgery by a water-jet hybrid knife in 10, and by

  20. Transurethral en bloc resection of bladder tumors

    Directory of Open Access Journals (Sweden)

    A. G. Martov

    2015-03-01

    Full Text Available Background. The high incidence of recurrent non-muscle-invasive bladder carcinoma (BC necessitates searches for new surgical methods. Objective: to comparatively evaluate the efficiency and safety of en block resection of bladder tumors versus transurethral resection (TUR. Subjects and methods. In January 2010 to June 2013, a total of 292 patients with primary and recurrent bladder tumor stages, cTa-T2, underwent transurethral endoscopic treatment (as TUR at the Unit of Minimally Invasive Urology, Moscow City Clinical Hospital Fifty-Seven. A major portion of these patients were included in the study of the efficiency and safety of en bloc TUR of bladder tumors. The criteria for study inclusion were primary or recurrent non-muscle-invasive bladder tumor measuring 1 to 3 cm, stage pTa-T1, signed informed consent to participate in the study and patients» readiness to undergo control examinations in inpatient setting for one year. The exclusion criteria were a confirmed or detected muscleinvasive tumor, multiple bladder involvement (> 3 tumors, as well as detected tumors spreading to the ureter, bladder neck, and prostatic urethra. The primary study endpoint was considered to be a recurrence of a tumor after TUR of the bladder (TURB. The secondary endpoint was the frequency of concealed bladder perforation, blood transfusions, recystoscopies for bladder tamponade, early recystoscopies to specify a BC stage, and the frequency of immediate intravesical injection of a chemical. For final analysis, the investigators selected 106 patients in a group where tumors were removed en bloc (a study group and 133 patients in a group where tumors were retrieved using traditional TURB (a control group. In the study group, the tumor was removed en bloc by a monopolar J-shaped electrode (sand wedge electrode in 45 patients, by a hook-like electrode in 14, by a hybrid procedure (hydropreparation and monopolar electrosurgery by a water-jet hybrid knife in 10, and by

  1. Ultrasound: Bladder (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Ultrasound: Bladder KidsHealth > For Parents > Ultrasound: Bladder A A A What's in this article? ... español Ultrasonido: vejiga What It Is A bladder ultrasound is a safe and painless test that uses ...

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

    Directory of Open Access Journals (Sweden)

    Tomokazu Ohishi

    2015-12-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Cheung Grace

    2013-01-01

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

  5. Magnetic resonace appearance of Gall Bladder Ascariasis

    Directory of Open Access Journals (Sweden)

    Arya Prafull

    2005-05-01

    Full Text Available Ascariasis is a common disease in many developing countries and is a common cause of biliary and pancreatic diseases in endemic areas. Numerous studies have been published on biliary tract ascariasis. All these have documented ultrasonography as the primary imaging modality for biliary tract ascariasis. Magnetic Resonance Cholangiopancreatography (MRCP has been the latest entrant for the study of bilary tract. MRCP findings of biliary tract ascariasis have been scarcely documented. MRCP is a unique non-invasive investigation for demonstrating ascariasis in Gall bladder and bilary tract clearly. We present MR appearances of Gall bladder and biliary tract in a proven case of biliary ascariasis.

  6. 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...

  7. ROLE OF USG AND MDCT IN EVALUATION OF URINARY BLADDER MASS

    Directory of Open Access Journals (Sweden)

    Sunny

    2014-11-01

    Full Text Available Primary bladder neoplasms account for 2%–6% of all tumors, with bladder cancer ranked as the fourth most common malignancy (1 . Peak incidence is in the sixth and the seventh decades. Incidence is four times higher in men than in women. The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible (or elastic organ, the bladder sits on the pelvic floor. Urine enters the bladder via the ureters and exits via the urethra. (2 The bladder is readily identified by ultrasound, Computed Tomography, cystography, Magnetic Resonance Image (MRI and Cystoscopy, but Bladder ultrasound is noninvasive, readily accessible, and easy to use. It has been extensively investigated as a possible substitution for some of the more common invasive modalities used to evaluate the bladder

  8. Modified spiral ileal orthotopic neobladder: Experience with 32 cases of invasive bladder cancer%改良原位螺旋构型回肠新膀胱术32例报告

    Institute of Scientific and Technical Information of China (English)

    王伟高; 钟欢; 俞彬; 汤建儿; 陈煜

    2011-01-01

    目的 评价原位螺旋构型回肠新膀胱术的疗效.方法 1998-2008年对32例男性膀胱癌患者行原位螺旋构型回肠新膀胱术.采用40~45 cm回肠新建储尿囊,去管后用无水乙醇擦拭以清除、破坏黏液细胞,螺旋状构型缝合成低压储尿囊.两侧输尿管末端袖口状整形后分别行原位"插入式"置入新膀胱(Split-Cuff术式).新建储尿囊采用"四针法"低位与尿道缝合.结果 本组平均手术时间(281.2±48.7)min;平均失血量(545.4±181.9)ml,术中输血20例,平均输血(430.8±235.9)ml;平均住院时间(26.8±9.7)d.白天控尿良好30例(93.7%),夜间控尿良好26例(81.3%).23例于术后6个月复查尿动力学提示新膀胱初始尿意容量为270~420(315.0±33.4)ml,最大膀胱容量350~600(490.3±39.7)ml,充盈压(22.5±11.8)cm H2O,最大排尿压(78.3±14.7)cm H2O,最大尿流率(16.5±5.9)ml/s.术后随访22~132个月,平均58.4个月,术后2年内死于肿瘤转移4例.结论 原位螺旋形回肠新膀胱具有容量大、相对低压、顺应性好、肠管利用率高、消化道干扰小和术后排尿、控尿功能更接近正常生理等特点.新膀胱经无水乙醇处理后减少了分泌吸收功能,降低了尿路梗阻和代谢紊乱发生率.输尿管新膀胱Split-Cuff乳头"插入式"吻合可有效防止尿液反流,且方法简单,不易引起管口狭窄,有效地保护了肾功能.尿道以"四针法"吻合简单、实用,可减少吻合口狭窄的发生率.改良螺旋构型回肠新膀胱术是一种较为合理的原位膀胱替代方法.%Objective To assess the outcomes of modified spiral ileal orthotopic neobladder.Methods From January 1998 to January 2008, 32 patients (all male) underwent radical cystectomy and spiral ileal orthotopic substitution for muscle invasive bladder cancer. A segment of 40 to 45 cm ileal loop was isolated, detubularized, and reconfigured in spiral shape to form a pouch. Bilateral ureters were reimplanted by inserting the

  9. Retrospective study of various conservative treatment options with bacille Calmette-Guérin in bladder urothelial carcinoma T1G3: Maintenance therapy.

    Science.gov (United States)

    Palou-Redorta, J; Solsona, E; Angulo, J; Fernández, J M; Madero, R; Unda, M; Martínez-Piñeiro, J A; Portillo, J; Chantada, V; Moyano, J L

    2016-01-01

    To compare various conservative treatment options for high-grade T1 nonmuscle-invasive bladder cancer (NMIBC). Bacille Calmette-Guérin (BCG) is the preferred intravesical treatment for high-grade T1 tumours; however, a number of experts still question the need for maintenance BCG. We retrospectively analysed data from 1039 patients with primary and recurrent T1G3 NMIBC. All patients underwent complete transurethral resection of the bladder tumour (TURBT), with muscle in the sample and multiple bladder biopsies. The patients were treated with the following: only one initial TURBT (n=108), re-TURBT (n=153), induction with 27mg of BCG (Connaught strain) (n=87), induction with 81mg of BCG (n=489) or induction with 81mg of BCG+maintenance (n=202). The time to first recurrence, progression (to T2 or greater or to metastatic disease) and specific mortality of the disease was assessed using the Kaplan-Meier survival function and were compared using the log-rank test and the Cox multivariate regression model of proportional risks. The mean follow-up was 62±39 months. The risk of recurrence was significantly lower for the patients treated with maintenance therapy of 81mg of BCG than in the other treatment groups (P<.001). The risk of tumour progression was also significantly lower for the patients treated with maintenance BCG than for the patients treated only with one TURBT, re-TURBT and with induction therapy with 27mg of BCG (P=.0003). The specific disease mortality was significantly lower with BCG maintenance (9.4%) than with only one TURBT (27.8%; P=.003). In the case of T1G3 NMIBC, a complete dose of BCG with maintenance is associated with better recurrence results than are other conservative treatment modalities. The results of progression and survival specific to the disease were also better with induction BCG, with or without maintenance. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. 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

    2015-12-01

    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. 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. 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. Our results suggest that the investigated polymorphisms influence patient response

  11. The Danish Bladder Cancer Database

    Directory of Open Access Journals (Sweden)

    Hansen E

    2016-10-01

    Full Text Available Erik Hansen,1–3 Heidi Larsson,4 Mette Nørgaard,4 Peter Thind,3,5 Jørgen Bjerggaard Jensen1–3 1Department of Urology, Hospital of West Jutland-Holstebro, Holstebro, 2Department of Urology, Aarhus University Hospital, Aarhus, 3The Danish Bladder Cancer Database Group, 4Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, 5Department of Urology, Copenhagen University Hospital, Copenhagen, Denmark Aim of database: The aim of the Danish Bladder Cancer Database (DaBlaCa-data is to monitor the treatment of all patients diagnosed with invasive bladder cancer (BC in Denmark. Study population: All patients diagnosed with BC in Denmark from 2012 onward were included in the study. Results presented in this paper are predominantly from the 2013 population. Main variables: In 2013, 970 patients were diagnosed with BC in Denmark and were included in a preliminary report from the database. A total of 458 (47% patients were diagnosed with non-muscle-invasive BC (non-MIBC and 512 (53% were diagnosed with muscle-invasive BC (MIBC. A total of 300 (31% patients underwent cystectomy. Among the 135 patients diagnosed with MIBC, who were 75 years of age or younger, 67 (50% received neoadjuvent chemotherapy prior to cystectomy. In 2013, a total of 147 patients were treated with curative-intended radiation therapy. Descriptive data: One-year mortality was 28% (95% confidence interval [CI]: 15–21. One-year cancer-specific mortality was 25% (95% CI: 22–27%. One-year mortality after cystectomy was 14% (95% CI: 10–18. Ninety-day mortality after cystectomy was 3% (95% CI: 1–5 in 2013. One-year mortality following curative-intended radiation therapy was 32% (95% CI: 24–39 and 1-year cancer-specific mortality was 23% (95% CI: 16–31 in 2013. Conclusion: This preliminary DaBlaCa-data report showed that the treatment of MIBC in Denmark overall meet high international academic standards. The database is able to identify Danish BC patients and

  12. Laparoscopic gastrocystoplasty for tuberculous contracted bladder

    Directory of Open Access Journals (Sweden)

    Manickam Ramalingam

    2017-01-01

    Full Text Available The stomach is the preferred augmentation option for a contracted bladder in a patient with renal failure. A 49-year-old female presented with right solitary functioning kidney with tuberculous lower ureteric stricture and contracted bladder. Her creatinine was 2.8 mg%. By laparoscopic approach, right gastroepiploic artery based gastric flap was isolated using staplers and used for augmentation and ureteric replacement. At 6-month follow-up, her creatinine was 1.9 mg%, and bladder capacity was 250 ml. She had mild hematuria, which settled with proton pump inhibitors. Laparoscopic gastrocystoplasty is feasible and effective augmentation option in those with renal failure, giving the benefits of minimally invasive approach.

  13. Bladder cancer; Cancer de la Vessie

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-07-01

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

  14. Bladder carcinoma: MDCT cystography and virtual cystoscopy.

    Science.gov (United States)

    Panebianco, Valeria; Sciarra, Alessandro; Di Martino, Michele; Bernardo, Silvia; Vergari, Valeria; Gentilucci, Alessandro; Catalano, Carlo; Passariello, Roberto

    2010-06-01

    Bladder carcinoma is the most common tumor among the low urinary tract, accounting for 90% of cancer cases. Conventional cystoscopy represents the gold standard for diagnosis and local management of bladder carcinoma. As the prevalence of transitional cell carcinoma is four-fold greater in men than in women, the endoscopic procedure presents objective difficulties related to the length and bending of male urethra. The most important problems are represented by intense discomfort for the patient and bleeding; furthermore, the high cost, invasivity, and local complications such as infections and mechanical lesions are well-known drawbacks. Additionally, conventional cystoscopy does not provide information about extravescical extensions of the tumor. CT cystography, combined with virtual cystoscopy, is mandatory for TNM staging of the tumor and also is useful when conventional cystoscopy is inconclusive or cannot be performed. We presents the CT cystography findings with virtual endoscopy correlation and bladder carcinoma appearance.

  15. MOLECULAR PROGNOSTIC MARKERS OF URINE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    V. N. Pavlov

    2012-01-01

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

  16. [A pheochromocytoma of urinary bladder treated with neoadjuvant chemotherapy].

    Science.gov (United States)

    Ibuki, Naokazu; Komura, Kazumasa; Koyama, Kouhei; Inamoto, Teruo; Segawa, Naoki; Tanimoto, Keiji; Tuji, Motomu; Azuma, Haruhito; Katsuoka, Yoji

    2009-12-01

    A 69-year-old female presented with hypertension and a solid mass in the bladder on ultrasonography. Cystoscopy revealed a submucosal tumor in the right lateral wall of the bladder. A transurethral resection was performed. Histologically, pathologic examination revealed a malignant pheochromocytoma. She refused surgical therapy and radiation therapy. She had no treatment for two years. She suddenly complained of gross hematuria. T2-weighted magnetic resonance imaging showed a bladder tumor of high intensity and extra-bladder invasion. She was treated with chemotherapy (CVD) for 26 cycles. Since the tumor size was reduced, she was referred to our hospital for operative indication. Partial cystectomy was performed. Histologically, the tumor was a pheochromocytoma of the urinary bladder. Ten months after the operation, she has no clinical evidence of recurrence.

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

    OpenAIRE

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

    1998-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

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

  19. Management of the urethra in urothelial bladder cancer

    OpenAIRE

    Kanaroglou, Androniki; Shayegan, Bobby

    2009-01-01

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

  20. Mouse bladder wall injection.

    Science.gov (United States)

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

    2011-07-12

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

  1. URACHAL CARCINOMA IN BLADDER

    Institute of Scientific and Technical Information of China (English)

    薛丽燕; 吕宁; 何祖根; 林冬梅; 刘秀云

    2004-01-01

    Objective: To investigate the clinicopathologic features and diagnostic criteria of urachal carcinoma in the bladder.Methods: Seven cases of urachal carcinoma in the bladder were analyzed retrospectively. Results: All the tumors were found locating in the dome of bladder. Of them, 4 were mucinous adenocarcinoma, one was well differentiated papillary enteric adenocarcinoma, one was well differentiated squamous carcinoma, and one was neuroendocrine carcinoma. Cystomorphous urachal remnants were found in 4 cases. The main complaint was hematuria and all patients underwent partial excision of bladder and urachus. Conclusion: Mucinous adenocarcinoma is the main histo-pathological type, and cystomorphous urachal remnants are often accompanied with urachal carcinoma in the bladder. The key diagnostic criteria of urachal carcinoma in bladder are site and histopathology. And to examine the specimens carefully to find the urachal remnants is important.

  2. 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 ...

  3. Bladder pain syndrome

    DEFF Research Database (Denmark)

    Hanno, Philip; Nordling, Jørgen; Fall, Magnus

    2011-01-01

    Bladder pain syndrome is a deceptively intricate symptom complex that is diagnosed on the basis of chronic pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder, accompanied by at least one other urinary symptom. It is a diagnosis of exclusion in a patient who has ex...... can be challenging, and misdiagnosis as a psychological problem, overactive bladder, or chronic urinary infection has plagued patients with the problem....

  4. Overactive bladder – 18 years – Part II

    Directory of Open Access Journals (Sweden)

    Jose Carlos Truzzi

    2016-04-01

    Full Text Available ABSTRACT Traditionally, the treatment of overactive bladder syndrome has been based on the use of oral medications with the purpose of reestablishing the detrusor stability. The recent better understanding of the urothelial physiology fostered conceptual changes, and the oral anticholinergics – pillars of the overactive bladder pharmacotherapy – started to be not only recognized for their properties of inhibiting the detrusor contractile activity, but also their action on the bladder afference, and therefore, on the reduction of the symptoms that constitute the syndrome. Beta-adrenergic agonists, which were recently added to the list of drugs for the treatment of overactive bladder, still wait for a definitive positioning – as either a second-line therapy or an adjuvant to oral anticholinergics. Conservative treatment failure, whether due to unsatisfactory results or the presence of adverse side effects, define it as refractory overactive bladder. In this context, the intravesical injection of botulinum toxin type A emerged as an effective option for the existing gap between the primary measures and more complex procedures such as bladder augmentation. Sacral neuromodulation, described three decades ago, had its indication reinforced in this overactive bladder era. Likewise, the electric stimulation of the tibial nerve is now a minimally invasive alternative to treat those with refractory overactive bladder. The results of the systematic literature review on the oral pharmacological treatment and the treatment of refractory overactive bladder gave rise to this second part of the review article Overactive Bladder – 18 years, prepared during the 1st Latin-American Consultation on Overactive Bladder.

  5. Overactive bladder – 18 years – Part II

    Science.gov (United States)

    Truzzi, Jose Carlos; Gomes, Cristiano Mendes; Bezerra, Carlos A.; Plata, Ivan Mauricio; Campos, Jose; Garrido, Gustavo Luis; Almeida, Fernando G.; Averbeck, Marcio Augusto; Fornari, Alexandre; Salazar, Anibal; Dell’Oro, Arturo; Cintra, Caio; Sacomani, Carlos Alberto Ricetto; Tapia, Juan Pablo; Brambila, Eduardo; Longo, Emilio Miguel; Rocha, Flavio Trigo; Coutinho, Francisco; Favre, Gabriel; Garcia, José Antonio; Castaño, Juan; Reyes, Miguel; Leyton, Rodrigo Eugenio; Ferreira, Ruiter Silva; Duran, Sergio; López, Vanda; Reges, Ricardo

    2016-01-01

    ABSTRACT Traditionally, the treatment of overactive bladder syndrome has been based on the use of oral medications with the purpose of reestablishing the detrusor stability. The recent better understanding of the urothelial physiology fostered conceptual changes, and the oral anticholinergics – pillars of the overactive bladder pharmacotherapy – started to be not only recognized for their properties of inhibiting the detrusor contractile activity, but also their action on the bladder afference, and therefore, on the reduction of the symptoms that constitute the syndrome. Beta-adrenergic agonists, which were recently added to the list of drugs for the treatment of overactive bladder, still wait for a definitive positioning – as either a second-line therapy or an adjuvant to oral anticholinergics. Conservative treatment failure, whether due to unsatisfactory results or the presence of adverse side effects, define it as refractory overactive bladder. In this context, the intravesical injection of botulinum toxin type A emerged as an effective option for the existing gap between the primary measures and more complex procedures such as bladder augmentation. Sacral neuromodulation, described three decades ago, had its indication reinforced in this overactive bladder era. Likewise, the electric stimulation of the tibial nerve is now a minimally invasive alternative to treat those with refractory overactive bladder. The results of the systematic literature review on the oral pharmacological treatment and the treatment of refractory overactive bladder gave rise to this second part of the review article Overactive Bladder – 18 years, prepared during the 1st Latin-American Consultation on Overactive Bladder. PMID:27176185

  6. Diabetic bladder dysfunction

    Institute of Scientific and Technical Information of China (English)

    Guiming Liu; Firouz Daneshgari

    2014-01-01

    Objective To review studies on diabetic bladder dysfunction (DBD),a common and bothersome complication of diabetes mellitus.Data sources We performed a search of the English literature through PubMed.The key words used were "diabetes" and "bladder dysfunction" or "cystopathy".Our own data and perspective are included in the discussion.Study selection Studies containing data relevant to DBD were selected.Because of the limited length of this article,we also referenced reviews that contain comprehensive amalgamations of relevant literature.Results The classic symptoms of DBD are decreased bladder sensation,increased bladder capacity,and impaired bladder emptying with resultant elevated post-void residual urine.However,recent clinical and experimental evidence indicate a strong presence of storage problems such as urge incontinence in diabetes.Recent studies of DBD in animal models of type 1 diabetes have revealed temporal effects of diabetes,causing an early phase of compensatory bladder function and a later phase of decompensated bladder function.The pathophysiology of DBD is multifactorial,including disturbances of the detrusor,urothelium,autonomic nerves,and urethra.Polyuria and hyperglycemia play important but distinctive roles in induction of bladder dysfunction in type 1 diabetes.Polyuria causes significant bladder hypertrophy in the early stage of diabetes,whereas oxidative stress in the bladder caused by chronic hyperglycemia may play an important role in the late stage failure of bladder function.Conclusions DBD includes time-dependent and mixed manifestations.The pathological alterations include muscle,nerve,and urothelium.Polyuria and hyperglycemia independently contribute to the pathogenesis of DBD.Treatments for DBD are limited.Future clinical studies on DBD in type 1 and type 2 diabetes should be investigated separately.Animal studies of DBD in type 2 diabetes are needed,from the natural history to mechanisms.Further understanding of the molecular

  7. Internal iliac artery embolisation for intractable bladder haemorrhage in the peri-operative phase

    Science.gov (United States)

    Gujral, S.; Bell, R.; Kabala, J.; Persad, R.

    1999-01-01

    Intractable haemorrhage from the bladder wall during transurethral resection of bladder tumour is uncommon but potentially catastrophic. Internal iliac artery embolisation is a minimally invasive technique, which is now widely practised to stop bleeding from branches of these arteries in situations including pelvic malignancy, obstetric and gynaecological emergencies and trauma. We report its successful use peri-operatively, in an unfit, elderly patient with uncontrolled bleeding.


Keywords: embolisation; internal iliac artery; transurethral resection of bladder tumour PMID:10448498

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

    DEFF Research Database (Denmark)

    Zieger, Karsten; Marcussen, Niels; Borre, Michael

    2009-01-01

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

  9. Bladder pain syndrome

    DEFF Research Database (Denmark)

    Hanno, Philip; Nordling, Jørgen; Fall, Magnus

    2011-01-01

    Bladder pain syndrome is a deceptively intricate symptom complex that is diagnosed on the basis of chronic pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder, accompanied by at least one other urinary symptom. It is a diagnosis of exclusion in a patient who has...

  10. Memory Disrupting Effects of Nonmuscle Myosin II Inhibition Depend on the Class of Abused Drug and Brain Region

    Science.gov (United States)

    Briggs, Sherri B.; Blouin, Ashley M.; Young, Erica J.; Rumbaugh, Gavin; Miller, Courtney A.

    2017-01-01

    Depolymerizing actin in the amygdala through nonmuscle myosin II inhibition (NMIIi) produces a selective, lasting, and retrieval-independent disruption of the storage of methamphetamine-associated memories. Here we report a similar disruption of memories associated with amphetamine, but not cocaine or morphine, by NMIIi. Reconsolidation appeared…

  11. Memory Disrupting Effects of Nonmuscle Myosin II Inhibition Depend on the Class of Abused Drug and Brain Region

    Science.gov (United States)

    Briggs, Sherri B.; Blouin, Ashley M.; Young, Erica J.; Rumbaugh, Gavin; Miller, Courtney A.

    2017-01-01

    Depolymerizing actin in the amygdala through nonmuscle myosin II inhibition (NMIIi) produces a selective, lasting, and retrieval-independent disruption of the storage of methamphetamine-associated memories. Here we report a similar disruption of memories associated with amphetamine, but not cocaine or morphine, by NMIIi. Reconsolidation appeared…

  12. Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history of MYH9-related disease

    DEFF Research Database (Denmark)

    Pecci, A.; Panza, E.; Pujol-Moix, N.

    2008-01-01

    MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in MYH9, the gene for the heavy chain of nonmuscle myosin IIA (NMMHC-IIA). All patients present from birth with macrothrombocytopenia, but in infancy or adult life, some of them develop sensorineural deafness...

  13. Clinical significance of the reduction of UT-B expression in urothelial carcinoma of the bladder.

    Science.gov (United States)

    Li, Chun; Xue, Haogang; Lei, Yanming; Zhu, Jianqiang; Yang, Baoxue; Gai, Xiaodong

    2014-12-01

    Urea transporter B (UT-B) is a membrane protein and plays an important role in regulating urea concentration in bladder urothelial cells. It has been reported that UT-B gene mutations were related to bladder carcinogenesis, and UT-B deletion could induce DNA damage and apoptosis in bladder urothelium. However, the functions and clinical significance of UT-B in human bladder cancer remain unknown. The most common type of bladder cancer is urothelial carcinoma (UC). We hypothesized that UT-B expression was related to bladder UC progress. In this study, UT-B was detected using immunohistochemistry in 52 paraffin-embedded specimens of bladder UC and 10 normal urothelium specimens. The results showed that UT-B protein expression in UC tumor cells was significantly lower as compared with normal urothelial cells (P = 0.021). UT-B protein expression was significantly reduced with increasing histological grade (P = 0.010). UT-B protein expression in muscle-invasive stage was significantly lower than in non-muscle-invasive stage (P = 0.014). Taken together, our data suggest that the reduction or loss of UT-B expression may be related to the incidence, progression and invasiveness of bladder UC. UT-B may be a novel diagnostic or prognostic biomarker, as well as a potential therapeutic target in UC of the bladder.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  15. A clinicoepidemiological study of young age bladder tumors: An eastern Indian scenario

    Directory of Open Access Journals (Sweden)

    Jitendra Pratap Singh

    2016-01-01

    Conclusion: The incidence of bladder cancer is common in younger age group. Active and passive cigarette smoking, tea, coffee intake, and exposure to organic dyes are major risk factor for younger age group bladder tumor in this part of world. TCC is most common histological subtype and most of them are in low grade without muscle invasion.

  16. Role of LARP6 and nonmuscle myosin in partitioning of collagen mRNAs to the ER membrane.

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    Hao Wang

    Full Text Available Type I collagen is extracellular matrix protein composed of two α1(I and one α2(I polypeptides that fold into triple helix. Collagen polypeptides are translated in coordination to synchronize the rate of triple helix folding to the rate of posttranslational modifications of individual polypeptides. This is especially important in conditions of high collagen production, like fibrosis. It has been assumed that collagen mRNAs are targeted to the membrane of the endoplasmic reticulum (ER after translation of the signal peptide and by signal peptide recognition particle (SRP. Here we show that collagen mRNAs associate with the ER membrane even when translation is inhibited. Knock down of LARP6, an RNA binding protein which binds 5' stem-loop of collagen mRNAs, releases a small amount of collagen mRNAs from the membrane. Depolimerization of nonmuscle myosin filaments has a similar, but stronger effect. In the absence of LARP6 or nonmuscle myosin filaments collagen polypeptides become hypermodified, are poorly secreted and accumulate in the cytosol. This indicates lack of coordination of their synthesis and retro-translocation due to hypermodifications and misfolding. Depolimerization of nonmuscle myosin does not alter the secretory pathway through ER and Golgi, suggesting that the role of nonmuscle myosin is primarily to partition collagen mRNAs to the ER membrane. We postulate that collagen mRNAs directly partition to the ER membrane prior to synthesis of the signal peptide and that LARP6 and nonmuscle myosin filaments mediate this process. This allows coordinated initiation of translation on the membrane bound collagen α1(I and α2(I mRNAs, a necessary step for proper synthesis of type I collagen.

  17. The Danish Bladder Cancer Database

    DEFF Research Database (Denmark)

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

    2016-01-01

    AIM OF DATABASE: The aim of the Danish Bladder Cancer Database (DaBlaCa-data) is to monitor the treatment of all patients diagnosed with invasive bladder cancer (BC) in Denmark. STUDY POPULATION: All patients diagnosed with BC in Denmark from 2012 onward were included in the study. Results......-intended radiation therapy. DESCRIPTIVE DATA: One-year mortality was 28% (95% confidence interval [CI]: 15-21). One-year cancer-specific mortality was 25% (95% CI: 22-27%). One-year mortality after cystectomy was 14% (95% CI: 10-18). Ninety-day mortality after cystectomy was 3% (95% CI: 1-5) in 2013. One......-year mortality following curative-intended radiation therapy was 32% (95% CI: 24-39) and 1-year cancer-specific mortality was 23% (95% CI: 16-31) in 2013. CONCLUSION: This preliminary DaBlaCa-data report showed that the treatment of MIBC in Denmark overall meet high international academic standards. The database...

  18. Application of fresh first morning midstream urine in cytological study of bladder cancer patients%晨起第一次新鲜中段尿用于膀胱癌细胞学诊断的临床价值

    Institute of Scientific and Technical Information of China (English)

    陈岳; 徐勇; 王锦; 刘冉录; 杨阔; 张昌文; 马宝杰; 张志宏; 乔宝民

    2010-01-01

    Objective To investigate the value of the application of the fresh first morning midstream urine in cytological study of bladder cancer patients. Methods The results of the fresh first and second morning midstream urine cytological studies for 52 bladder cancer patients were analyzed.Continual three urine samples and single urine sample were treated as study objects respectively. The positive rates in different tumor stages and grades were evaluated. Results The positive rate of overall 52 patients was 78. 8 % (41/52) in fresh first morning midstream urine and 80. 8% ( 42 / 52) in the fresh second morning midstream urine. While in 156 single urine samples, the positive percentages were 56.4%(88/156) and 60. 9% (95/156). The positive rates of the fresh first and second morning midstream urine were 69.7% (23/33) and 72.7% (24/33) respectively in grade 1- 2 patients, and 44.4 % (44/99) and 48. 5 % (48/99) in 99 single urine samples. The positive rates of 42 non-muscle invasive bladder cancer patients were 73. 8% (31/42) and 76.2% (32/42) in the fresh first and second morning midstream urine, while in 126 single urine samples, the positive rates were 54.8% (69/126)and 57.1% (72/126). There were no significant differences between positive rate of the fresh first and second morning midstream urine in diagnosis of bladder cancer, low grade bladder cancer and nonmuscle invasive bladder cancer. Conclusion The fresh first morning midstream urine can be used for urine cytological study in the diagnosis of bladder cancer, even in the diagnosis of low stage and low grade bladder cancer.%目的 探讨晨起第一次中段尿脱落细胞学检查诊断膀胱癌的临床价值. 方法 分析52例经活检或手术病理确诊为膀胱癌患者晨起第一、二次新鲜中段尿脱落细胞学检查结果,以连续3 d标本结果和单次标本结果为研究对象,按总体、病理分级及临床分期分别计算2个时段尿脱落细胞阳性率,并进行统计学分析.

  19. Paraganglioma of urinary bladder

    Directory of Open Access Journals (Sweden)

    Vinod Priyadarshi

    2015-01-01

    Full Text Available Paraganglioma of the urinary bladder are tumors of chromaffin tissue originating from the sympathetic innervations of the urinary bladder wall and are extremely rare. Being functional, in most of the cases they are recognized by their characteristic presentation of hypertensive crisis and postmicturition syncope. A silent presentation of a bladder paraganglioma is very unusual but quite dangerous as they are easily misdiagnosed and adequate peri-operative attention is not provided. Here, we are presenting one such silent paraganglioma in adult women who presented with only a single episode of hematuria and severe hypertensive crisis occur during its trans-urethral resection.

  20. Bladder Smooth Muscle Cells Differentiation from Dental Pulp Stem Cells: Future Potential for Bladder Tissue Engineering

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    Bing Song

    2016-01-01

    Full Text Available Dental pulp stem cells (DPSCs are multipotent cells capable of differentiating into multiple cell lines, thus providing an alternative source of cell for tissue engineering. Smooth muscle cell (SMC regeneration is a crucial step in tissue engineering of the urinary bladder. It is known that DPSCs have the potential to differentiate into a smooth muscle phenotype in vitro with differentiation agents. However, most of these studies are focused on the vascular SMCs. The optimal approaches to induce human DPSCs to differentiate into bladder SMCs are still under investigation. We demonstrate in this study the ability of human DPSCs to differentiate into bladder SMCs in a growth environment containing bladder SMCs-conditioned medium with the addition of the transforming growth factor beta 1 (TGF-β1. After 14 days of exposure to this medium, the gene and protein expression of SMC-specific marker (α-SMA, desmin, and calponin increased over time. In particular, myosin was present in differentiated cells after 11 days of induction, which indicated that the cells differentiated into the mature SMCs. These data suggested that human DPSCs could be used as an alternative and less invasive source of stem cells for smooth muscle regeneration, a technology that has applications for bladder tissue engineering.

  1. Life without double-headed non-muscle myosin II motor proteins

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    Venkaiah eBetapudi

    2014-07-01

    Full Text Available Non-muscle myosin II motor proteins (myosin IIA, myosin IIB, and myosin IIC belong to a class of molecular motor proteins that are known to transduce cellular free-energy into biological work more efficiently than man-made combustion engines. Nature has given a single myosin II motor protein for lower eukaryotes and multiple for mammals but none for plants in order to provide impetus for their life. These specialized nanomachines drive cellular activities necessary for embryogenesis, organogenesis, and immunity. However, these multifunctional myosin II motor proteins are believed to go awry due to unknown reasons and contribute for the onset and progression of many autosomal-dominant disorders, cataract, deafness, infertility, cancer, kidney, neuronal, and inflammatory diseases. Many pathogens like HIV, Dengue, hepatitis C, and Lymphoma viruses as well as Salmonella and Mycobacteria are now known to take hostage of these dedicated myosin II motor proteins for their efficient pathogenesis. Even after four decades since their discovery, we still have a limited knowledge of how these motor proteins drive cell migration and cytokinesis. We need to enrich our current knowledge on these fundamental cellular processes and develop novel therapeutic strategies to fix mutated myosin II motor proteins in pathological conditions. This is the time to think how to relieve the hijacked myosins from pathogens in order to provide a renewed impetus for patients’ life. Understanding how to steer these molecular motors in proliferating and differentiating stem cells will improve stem cell based-therapeutics development. Given the plethora of cellular activities non-muscle myosin motor proteins are involved in, their importance is apparent for human life.

  2. Life without double-headed non-muscle myosin II motor proteins

    Science.gov (United States)

    Betapudi, Venkaiah

    2014-07-01

    Non-muscle myosin II motor proteins (myosin IIA, myosin IIB, and myosin IIC) belong to a class of molecular motor proteins that are known to transduce cellular free-energy into biological work more efficiently than man-made combustion engines. Nature has given a single myosin II motor protein for lower eukaryotes and multiple for mammals but none for plants in order to provide impetus for their life. These specialized nanomachines drive cellular activities necessary for embryogenesis, organogenesis, and immunity. However, these multifunctional myosin II motor proteins are believed to go awry due to unknown reasons and contribute for the onset and progression of many autosomal-dominant disorders, cataract, deafness, infertility, cancer, kidney, neuronal, and inflammatory diseases. Many pathogens like HIV, Dengue, hepatitis C, and Lymphoma viruses as well as Salmonella and Mycobacteria are now known to take hostage of these dedicated myosin II motor proteins for their efficient pathogenesis. Even after four decades since their discovery, we still have a limited knowledge of how these motor proteins drive cell migration and cytokinesis. We need to enrich our current knowledge on these fundamental cellular processes and develop novel therapeutic strategies to fix mutated myosin II motor proteins in pathological conditions. This is the time to think how to relieve the hijacked myosins from pathogens in order to provide a renewed impetus for patients’ life. Understanding how to steer these molecular motors in proliferating and differentiating stem cells will improve stem cell based-therapeutics development. Given the plethora of cellular activities non-muscle myosin motor proteins are involved in, their importance is apparent for human life.

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

    Directory of Open Access Journals (Sweden)

    Ahmad Keshtkar

    2012-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2006-02-01

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

  6. Non-muscle myosin as target antigen for human autoantibodies in patients with hepatitis C virus-associated chronic liver diseases.

    Science.gov (United States)

    von Mühlen, C A; Chan, E K; Peebles, C L; Imai, H; Kiyosawa, K; Tan, E M

    1995-04-01

    Three patients with hepatitis C virus (HCV)-related chronic liver disease were shown to have autoantibodies strongly reacting with cytoskeletal fibres of non-muscle cells. The heavy chain of non-muscle myosin microfilament was the main target for those autoantibodies, as determined by (i) cell and tissue immunofluorescence studies showing colocalization with an anti-myosin antibody prototype; (ii) primary reactivity in immunoblotting with a 200-kD protein, using either MOLT-4 cells, human platelets, or affinity-purified non-muscle myosin as antigen extract; and (iii) immunoblotting of similar immunoreactive fragments in papain-digested MOLT-4 cell extracts, by using those human sera and antibody prototype. Autoantibodies to non-muscle myosin heavy chain were not previously reported in patients with chronic liver diseases, especially in those associated with HCV infection.

  7. Long neglected neurogenic bladder

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    Pooja Binnani

    2011-01-01

    Full Text Available Urinary diversion is indicated for the management of the neurogenic bladder. However, there is a risk for developing pyocystitis in this type of patients. We present a case of young female who presented with a history of frequent urinary tract infection (UTI post urinary diversion for neurogenic bladder. Ever since she underwent simple cystectomy, there have been no further episodes of UTI.

  8. Impedance ratio method for urine conductivity-invariant estimation of bladder volume

    Directory of Open Access Journals (Sweden)

    Thomas Schlebusch

    2014-09-01

    Full Text Available Non-invasive estimation of bladder volume could help patients with impaired bladder volume sensation to determine the right moment for catheterisation. Continuous, non-invasive impedance measurement is a promising technology in this scenario, although influences of body posture and unknown urine conductivity limit wide clinical use today. We studied impedance changes related to bladder volume by simulation, in-vitro and in-vivo measurements with pigs. In this work, we present a method to reduce the influence of urine conductivity to cystovolumetry and bring bioimpedance cystovolumetry closer to a clinical application.

  9. 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

  10. Spontaneous Bladder Perforation in an Infant Neurogenic Bladder: Laparoscopic Management

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    Daniel Cabezalí Barbancho

    2013-01-01

    Full Text Available Spontaneous bladder perforation is an uncommon event in childhood. It is usually associated with bladder augmentation. We are presenting a case of bladder rupture in an infant with neurogenic bladder without prior bladder surgery. Three days after lipomyelomeningocele excision the patient showed signs and symptoms of acute abdomen. The ultrasound exploration revealed significant amount of intraperitoneal free fluid and therefore a laparoscopic exploration was performed. A posterior bladder rupture was diagnosed and repaired laparoscopically. Currently, being 3 years old, she keeps successfully dry with clean intermittent catheterization. Neurogenic bladder voiding function can change at any time of its evolution and lead to complications. Early diagnosis of spontaneous bladder rupture is of paramount importance, so it is essential to think about it in the differential diagnosis of acute abdomen.

  11. Cyclase-associated Protein 1 (CAP1) Promotes Cofilin-induced Actin Dynamics in Mammalian Nonmuscle CellsV⃞

    OpenAIRE

    Bertling, Enni; Hotulainen, Pirta; Mattila, Pieta K.; Matilainen, Tanja; Salminen, Marjo; Lappalainen, Pekka

    2004-01-01

    Cyclase-associated proteins (CAPs) are highly conserved actin monomer binding proteins present in all eukaryotes. However, the mechanism by which CAPs contribute to actin dynamics has been elusive. In mammals, the situation is further complicated by the presence of two CAP isoforms whose differences have not been characterized. Here, we show that CAP1 is widely expressed in mouse nonmuscle cells, whereas CAP2 is the predominant isoform in developing striated muscles. In cultured NIH3T3 and B1...

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

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    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.

  13. Bladder Control Problems in Men

    Science.gov (United States)

    ... special sensors to measure bodily functions, such as muscle contractions that control urination. A video monitor displays the ... symptoms of urgency incontinence. Mirabegron suppresses involuntary bladder ... brain signals the muscular bladder wall to tighten, squeezing urine out of ...

  14. Giant Intradiverticular Bladder Tumor

    Science.gov (United States)

    Noh, Mohamad Syafeeq Faeez Md; Aziz, Ahmad Fuad Abdul; Ghani, Khairul Asri Mohd; Siang, Christopher Lee Kheng; Yunus, Rosna; Yusof, Mubarak Mohd

    2017-01-01

    Patient: Male, 74 Final Diagnosis: Giant intradiverticular bladder tumor with metastasis Symptoms: Hematuria Medication:— Clinical Procedure: — Specialty: Urology Objective: Rare disease Background: Intradiverticular bladder tumors are rare. This renders diagnosis of an intradiverticular bladder tumor difficult. Imaging plays a vital role in achieving the diagnosis, and subsequently staging of the disease. Case Report: A 74-year-old male presented to our center with a few months history of constitutional symptoms. Upon further history, he reported hematuria two months prior to presentation, which stopped temporarily, only to recur a few days prior to coming to the hospital. The patient admitted to having lower urinary tract symptoms. However, there was no dysuria, no sandy urine, and no fever. Palpation of his abdomen revealed a vague mass at the suprapubic region, which was non tender. In view of his history and the clinical examination findings, an ultrasound of the abdomen and computed tomography (CT) was arranged. These investigations revealed a giant tumor that seemed to be arising from a bladder diverticulum, with a mass effect and hydronephrosis. He later underwent operative intervention. Conclusions: Intradiverticular bladder tumors may present a challenge to the treating physician in an atypical presentation; thus requiring a high index of suspicion and knowledge of tumor pathophysiology. As illustrated in our case, CT with its wide availability and multiplanar imaging capabilities offers a useful means for diagnosis, disease staging, operative planning, and follow-up. PMID:28246375

  15. 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.

  16. Modulation of carcinogenesis in the urinary bladder by retinoids.

    Science.gov (United States)

    Hicks, R M; Turton, J A; Chowaniec, J; Tomlinson, C N; Gwynne, J; Nandra, K; Chrysostomou, E; Pedrick, M

    1985-01-01

    Bladder cancer has a 70% recurrence rate within five years and a high associated mortality. It commonly occurs in one or both of two predominant growth/behaviour patterns: either well-differentiated, relatively benign exophytic papillary lesions, or flat, poorly differentiated invasive carcinoma usually arising from carcinoma-in-situ. We have used the F344 rat treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) as a model for the papillary disease, and the BBN-treated B6D2F1 mouse for flat, invasive bladder carcinoma. In the rat, carcinogenesis is a multistage process and several retinoids will delay or even halt the development of bladder cancer. Inhibition of carcinogenesis is not complete, but there is a consistent reduction in the time-related incidence of papillomas and carcinomas and a concomitant improvement in the overall differentiation of the urothelium. In the BBN/mouse model, retinoids also have anticarcinogenic activity but interpretation of the results is more complicated. Unlike the F344 rat, the B6D2F1 mouse has a non-uniform response to BBN; not all mice develop bladder cancer even after treatment with very high doses of BBN and in those that do, more than one mechanism of carcinogenesis may be involved. Individual retinoids differ markedly in their ability to modulate bladder carcinogenesis in rodents; the behaviour of one analogue cannot be predicted automatically from data obtained with another. Combined data from rodent trials in this and other laboratories have identified N-(4-hydroxyphenyl)retinamide (HPR) as the most anticarcinogenic retinoid tested so far for the rodent bladder. It is also less toxic in rodents and better tolerated in humans than either 13-cis-retinoic acid or etretinate, two retinoids currently used in dermatological practice. A prophylactic chemopreventive trial of HPR in bladder cancer patients starting in 1985 will be centered on the Middlesex Hospital, London.

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

    Directory of Open Access Journals (Sweden)

    Thomas Reinert

    2012-01-01

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

  18. 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.

  19. Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration.

    Science.gov (United States)

    Morin, Nicole A; Oakes, Patrick W; Hyun, Young-Min; Lee, Dooyoung; Chin, Y Eugene; Chin, Eugene Y; King, Michael R; Springer, Timothy A; Shimaoka, Motomu; Tang, Jay X; Reichner, Jonathan S; Kim, Minsoo

    2008-01-21

    Precise spatial and temporal regulation of cell adhesion and de-adhesion is critical for dynamic lymphocyte migration. Although a great deal of information has been learned about integrin lymphocyte function-associated antigen (LFA)-1 adhesion, the mechanism that regulates efficient LFA-1 de-adhesion from intercellular adhesion molecule (ICAM)-1 during T lymphocyte migration is unknown. Here, we show that nonmuscle myosin heavy chain IIA (MyH9) is recruited to LFA-1 at the uropod of migrating T lymphocytes, and inhibition of the association of MyH9 with LFA-1 results in extreme uropod elongation, defective tail detachment, and decreased lymphocyte migration on ICAM-1, without affecting LFA-1 activation by chemokine CXCL-12. This defect was reversed by a small molecule antagonist that inhibits both LFA-1 affinity and avidity regulation, but not by an antagonist that inhibits only affinity regulation. Total internal reflection fluorescence microscopy of the contact zone between migrating T lymphocytes and ICAM-1 substrate revealed that inactive LFA-1 is selectively localized to the posterior of polarized T lymphocytes, whereas active LFA-1 is localized to their anterior. Thus, during T lymphocyte migration, uropodal adhesion depends on LFA-1 avidity, where MyH9 serves as a key mechanical link between LFA-1 and the cytoskeleton that is critical for LFA-1 de-adhesion.

  20. Nuclei of non-muscle cells bind centrosome proteins upon fusion with differentiating myoblasts.

    Directory of Open Access Journals (Sweden)

    Xavier Fant

    Full Text Available BACKGROUND: In differentiating myoblasts, the microtubule network is reorganized from a centrosome-bound, radial array into parallel fibres, aligned along the long axis of the cell. Concomitantly, proteins of the centrosome relocalize from the pericentriolar material to the outer surface of the nucleus. The mechanisms that govern this relocalization are largely unknown. METHODOLOGY: In this study, we perform experiments in vitro and in cell culture indicating that microtubule nucleation at the centrosome is reduced during myoblast differentiation, while nucleation at the nuclear surface increases. We show in heterologous cell fusion experiments, between cultures of differentiating mouse myoblasts and human cells of non-muscular origin, that nuclei from non-muscle cells recruit centrosome proteins once fused with the differentiating myoblasts. This recruitment still occurs in the presence of cycloheximide and thus appears to be independent of new protein biosynthesis. CONCLUSIONS: Altogether, our data suggest that nuclei of undifferentiated cells have the dormant potential to bind centrosome proteins, and that this potential becomes activated during myoblast differentiation.

  1. Non-muscle myosin II in disease: mechanisms and therapeutic opportunities

    Directory of Open Access Journals (Sweden)

    Karen A. Newell-Litwa

    2015-12-01

    Full Text Available The actin motor protein non-muscle myosin II (NMII acts as a master regulator of cell morphology, with a role in several essential cellular processes, including cell migration and post-synaptic dendritic spine plasticity in neurons. NMII also generates forces that alter biochemical signaling, by driving changes in interactions between actin-associated proteins that can ultimately regulate gene transcription. In addition to its roles in normal cellular physiology, NMII has recently emerged as a critical regulator of diverse, genetically complex diseases, including neuronal disorders, cancers and vascular disease. In the context of these disorders, NMII regulatory pathways can be directly mutated or indirectly altered by disease-causing mutations. NMII regulatory pathway genes are also increasingly found in disease-associated copy-number variants, particularly in neuronal disorders such as autism and schizophrenia. Furthermore, manipulation of NMII-mediated contractility regulates stem cell pluripotency and differentiation, thus highlighting the key role of NMII-based pharmaceuticals in the clinical success of stem cell therapies. In this Review, we discuss the emerging role of NMII activity and its regulation by kinases and microRNAs in the pathogenesis and prognosis of a diverse range of diseases, including neuronal disorders, cancer and vascular disease. We also address promising clinical applications and limitations of NMII-based inhibitors in the treatment of these diseases and the development of stem-cell-based therapies.

  2. Nonmuscle Myosin IIA Regulates Platelet Contractile Forces Through Rho Kinase and Myosin Light-Chain Kinase.

    Science.gov (United States)

    Feghhi, Shirin; Tooley, Wes W; Sniadecki, Nathan J

    2016-10-01

    Platelet contractile forces play a major role in clot retraction and help to hold hemostatic clots against the vessel wall. Platelet forces are produced by its cytoskeleton, which is composed of actin and nonmuscle myosin filaments. In this work, we studied the role of Rho kinase, myosin light-chain kinase, and myosin in the generation of contractile forces by using pharmacological inhibitors and arrays of flexible microposts to measure platelet forces. When platelets were seeded onto microposts, they formed aggregates on the tips of the microposts. Forces produced by the platelets in the aggregates were measured by quantifying the deflection of the microposts, which bent in proportion to the force of the platelets. Platelets were treated with small molecule inhibitors of myosin activity: Y-27632 to inhibit the Rho kinase (ROCK), ML-7 to inhibit myosin light-chain kinase (MLCK), and blebbistatin to inhibit myosin ATPase activity. ROCK inhibition reduced platelet forces, demonstrating the importance of the assembly of actin and myosin phosphorylation in generating contractile forces. Similarly, MLCK inhibition caused weaker platelet forces, which verifies that myosin phosphorylation is needed for force generation in platelets. Platelets treated with blebbistatin also had weaker forces, which indicates that myosin's ATPase activity is necessary for platelet forces. Our studies demonstrate that myosin ATPase activity and the regulation of actin-myosin assembly by ROCK and MLCK are needed for the generation of platelet forces. Our findings illustrate and explain the importance of myosin for clot compaction in hemostasis and thrombosis.

  3. SLIT2/ROBO2 signaling pathway inhibits nonmuscle myosin IIA activity and destabilizes kidney podocyte adhesion

    Science.gov (United States)

    Fan, Xueping; Yang, Hongying; Kumar, Sudhir; Tumelty, Kathleen E.; Pisarek-Horowitz, Anna; Sharma, Richa; Chan, Stefanie; Tyminski, Edyta; Shamashkin, Michael; Belghasem, Mostafa; Henderson, Joel M.; Coyle, Anthony J.; Berasi, Stephen P.

    2016-01-01

    The repulsive guidance cue SLIT2 and its receptor ROBO2 are required for kidney development and podocyte foot process structure, but the SLIT2/ROBO2 signaling mechanism regulating podocyte function is not known. Here we report that a potentially novel signaling pathway consisting of SLIT/ROBO Rho GTPase activating protein 1 (SRGAP1) and nonmuscle myosin IIA (NMIIA) regulates podocyte adhesion downstream of ROBO2. We found that the myosin II regulatory light chain (MRLC), a subunit of NMIIA, interacts directly with SRGAP1 and forms a complex with ROBO2/SRGAP1/NMIIA in the presence of SLIT2. Immunostaining demonstrated that SRGAP1 is a podocyte protein and is colocalized with ROBO2 on the basal surface of podocytes. In addition, SLIT2 stimulation inhibits NMIIA activity, decreases focal adhesion formation, and reduces podocyte attachment to collagen. In vivo studies further showed that podocyte-specific knockout of Robo2 protects mice from hypertension-induced podocyte detachment and albuminuria and also partially rescues the podocyte-loss phenotype in Myh9 knockout mice. Thus, we have identified SLIT2/ROBO2/SRGAP1/NMIIA as a potentially novel signaling pathway in kidney podocytes, which may play a role in regulating podocyte adhesion and attachment. Our findings also suggest that SLIT2/ROBO2 signaling might be a therapeutic target for kidney diseases associated with podocyte detachment and loss. PMID:27882344

  4. Expression of Annexin A2 and Its Correlation With Drug Resistance and Recurrence of Bladder Cancer.

    Science.gov (United States)

    Hu, Huihui; Zhao, Jin; Zhang, Man

    2016-12-01

    To explore the expressions of annexin A2 in bladder cancer cell lines and bladder cancer tissues, we want to find the relationship among annexin A2, drug resistance, and recurrence of bladder cancer. Our laboratory established the PUMC-91 bladder cancer cell line against gradient concentration of Adriamycin (0.3, 0.6, and 1.0 μg/mL), and we also collected 60 cases of surgically resected bladder cancer recurrent tissue samples. The tissues were classified into 2 groups according to the frequency of recurrence (2 years) after initial surgery. The method of immunohistochemistry was used to examine the differences in the expression of annexin A2. There were statistical differences in annexin A2 among normal bladder epithelial cell line SV-HUC-1, PUMC-91, PUMC-91 against 0.3 μg/mL Adriamycin, and PUMC-91 against 1.0 μg/mL Adriamycin (P 2 years (P = .002) in the bladder cancer tissues and that recurred at <6 months after initial surgery. It was also associated with invasion depth (stage) of bladder cancer, such as higher expression in T2 (invasive muscular) group than Tis (carcinoma in situ) and T1 (invasive mucosa lamina propria) groups (P = .003 and P = .000, respectively). But, it did not correlate with the differentiation (grade) of cancer cells in bladder cancer tissues (P = .593). Annexin A2 can act as a valuable biomarker for predicting the drug resistance and recurrence of bladder cancer. © The Author(s) 2015.

  5. Enterovesical Fistula Secondary to Squamous Cell Carcinoma of the Bladder.

    Science.gov (United States)

    Sellers, William; Fiorelli, Robert

    2015-11-01

    Enterovesical fistulas are a well-known complication of inflammatory and malignant bowel disease. Bladder carcinoma, however, is an extremely rare etiology. We describe a case of squamous cell carcinoma of the bladder with an enterovesical fistula. This rare phenomenon has never been previously reported in western literature. We review the diagnosis, work up and treatment of enterovesical fistulas. Unfortunately, the prognosis for these highly invasive tumors is very poor and the treatment is often palliative. The high morbidity and mortality makes management of these patients exceptionally challenging.

  6. Electrical impedance spectroscopy and the diagnosis of bladder pathology.

    Science.gov (United States)

    Keshtkar, Ahmad; Keshtkar, Asghar; Smallwood, Rod H

    2006-07-01

    Bladder pathology is usually investigated visually by cystoscopy. At present, definitive diagnosis of the bladder can be made by biopsy only, usually under general anaesthesia. This is a relatively high-cost procedure in terms of both time and money and is associated with discomfort for the patient and morbidity. Thus, we used an electrical impedance spectroscopy technique for differentiating pathological changes in the urothelium and improving cystoscopic detection. For ex vivo study, a whole or part of the patient's urinary bladder was used to take the readings less than half an hour after excision at room temperature, about 27 degrees C, using the Mk3.5 Sheffield System (2-384 kHz in 24 frequencies). In this study, 145 points (from 16 freshly excised bladders from patients) were studied in terms of their biopsy reports matching to the electrical impedance measurements. For in vivo study, a total of 106 points from 38 patients were studied to take electrical impedance and biopsy samples. The impedance data were evaluated in both malignant and benign groups, and revealed a significant difference between these two groups. The impedivity of the malignant bladder tissue was significantly higher than the impedivity of the benign tissue, especially at lower frequencies (p < 0.001). In addition, the receiver operating characteristic (ROC) curve for impedance measurements indicated that this technique could provide diagnostic information (individual classification is possible). Thus, the authors have investigated the application of bio-impedance measurements to the bladder tissue as a novel and minimally invasive technique to characterize human bladder urothelium. Therefore, this technique, especially at lower frequencies, can be a complementary method for cystoscopy, biopsy and histopathological evaluation of the bladder abnormalities.

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

    DEFF Research Database (Denmark)

    Primdahl, Hanne; Maase, Hans von der; Sørensen, Flemming B.

    2002-01-01

    PURPOSE: The cell cycle is known to be deregulated in cancer. We therefore analyzed the expression of the cell cycle related proteins p21, p27, p16, Rb, and L-myc by immunohistochemical staining of bladder tumors. METHODS: The tissue material consisted of bladder tumors from three groups......(kip1) ( P=0.03), Rb ( P=0.00002), and L-myc ( P=0.00000007) in muscle invasive tumors compared to noninvasive tumors. Tumors presenting as muscle invasive at first diagnosis had significantly lower levels of p16/CDKN2A ( P=0.01) when compared to muscle invasive tumors that followed Ta or T1 precursor...

  8. Tissue-engineered conduit using bladder acellular matrix and bladder epithelial cells for urinary diversion in rabbits

    Institute of Scientific and Technical Information of China (English)

    LIAO Wen-biao; SONG Chao; LI Yong-wei; YANG Si-xing; MENG Lin-chao; LI Xin-hui

    2013-01-01

    Background For muscle invasive bladder cancer,radical cystectomy is the most effective treatment now and urinary diversion is often necessary.The use of intestinal tissue for urinary diversion is frequently associated with complications.In this study,we aimed to make a tissue-engineered conduit (TEC) using bladder epithelial cells and bladder acellular matrix (BAM) for urinary diversion in rabbits.Methods Bladder epithelial cells of rabbit were cultivated and expanded in vitro,then seeded on BAM,and cultured for 7 days.Then cell-seeded graft was used to make TEC.In the experimental group,most of bladder of the rabbit was removed while bladder trigone was retained.The proximal end of TEC was anastomosed with bladder trigone and the distal end was anastomosed with the abdominal stoma.In the control group,TEC was made using unseeded BAM.Haematoxylin and eosin staining was conducted,respectively,at 1,2,4,and 8 weeks postoperatively.Immunohistochemistry was performed 8 weeks postoperatively.Intravenous urography,retrograde pyelography,and cystoscopy of TEC were made at 12 weeks postoperatively.Results All animals were alive in the experimental group.Haematoxylin and eosin staining showed epithelial coverage in TEC.Immunohistochemistry showed anti-cytokeratin AE1/AE3 antibody and anti-ZO1 antibody positive,confirming there were mature and functional epithelial cells on the lumen of TEC.Retrograde pyelography and intravenous urography showed that TEC developed well and that there was no obstruction.In the control group,four rabbits were dead within 2 weeks and scar formation,atresia,and severe hydronephrosis were found.Conclusions We successfully made TEC using BAM and bladder epithelial cells for urinary diversion in rabbits.The lumen of this new TEC covered mature epithelial cells and could prevent urinary extravasation.

  9. Surveillance of bladder cancer

    NARCIS (Netherlands)

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

    2009-01-01

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

  10. Supplementary Material for: Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer

    KAUST Repository

    Roperch, Jean-Pierre

    2016-01-01

    Abstract Background Non-muscle-invasive bladder cancer (NMIBC) is a high incidence form of bladder cancer (BCa), where genetic and epigenetic alterations occur frequently. We assessed the performance of associating a FGFR3 mutation assay and a DNA methylation analysis to improve bladder cancer detection and to predict disease recurrence of NMIBC patients. Methods We used allele specific PCR to determine the FGFR3 mutation status for R248C, S249C, G372C, and Y375C. We preselected 18 candidate genes reported in the literature as being hypermethylated in cancer and measured their methylation levels by quantitative multiplex-methylation specific PCR. We selected HS3ST2, SLIT2 and SEPTIN9 as the most discriminative between control and NMIBC patients and we assayed these markers on urine DNA from a diagnostic study consisting of 167 NMIBC and 105 controls and a follow-up study consisting of 158 NMIBC at diagnosis time’s and 425 at follow-up time. ROC analysis was performed to evaluate the diagnostic accuracy of each assay alone and in combination. Results For Diagnosis: Using a logistic regression analysis with a model consisting of the 3 markers’ methylation values, FGFR3 status, age and known smoker status at the diagnosis time we obtained sensitivity/specificity of 97.6 %/84.8 % and an optimism-corrected AUC of 0.96. With an estimated BCa prevalence of 12.1 % in a hematuria cohort, this corresponds to a negative predictive value (NPV) of 99.6 %. For Follow-up: Using a logistic regression with FGFR3 mutation and the CMI at two time points (beginning of the follow-up and current time point), we got sensitivity/specificity/NPV of 90.3 %/65.1 %/97.0 % and a corrected AUC of 0.84. We also tested a thresholding algorithm with FGFR3 mutation and the two time points as described above, obtaining sensitivity/specificity/NPV values of, respectively, 94.5 %/75.9 %/98.5 % and an AUC of 0.82. Conclusions We showed that combined analysis of FGFR3 mutation and DNA

  11. Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer

    KAUST Repository

    Roperch, Jean-Pierre

    2016-09-02

    Background: Non-muscle-invasive bladder cancer (NMIBC) is a high incidence form of bladder cancer (BCa), where genetic and epigenetic alterations occur frequently. We assessed the performance of associating a FGFR3 mutation assay and a DNA methylation analysis to improve bladder cancer detection and to predict disease recurrence of NMIBC patients. Methods: We used allele specific PCR to determine the FGFR3 mutation status for R248C, S249C, G372C, and Y375C. We preselected 18 candidate genes reported in the literature as being hypermethylated in cancer and measured their methylation levels by quantitative multiplex-methylation specific PCR. We selected HS3ST2, SLIT2 and SEPTIN9 as the most discriminative between control and NMIBC patients and we assayed these markers on urine DNA from a diagnostic study consisting of 167 NMIBC and 105 controls and a follow-up study consisting of 158 NMIBC at diagnosis time\\'s and 425 at follow-up time. ROC analysis was performed to evaluate the diagnostic accuracy of each assay alone and in combination. Results: For Diagnosis: Using a logistic regression analysis with a model consisting of the 3 markers\\' methylation values, FGFR3 status, age and known smoker status at the diagnosis time we obtained sensitivity/specificity of 97.6 %/84.8 % and an optimism-corrected AUC of 0.96. With an estimated BCa prevalence of 12.1 % in a hematuria cohort, this corresponds to a negative predictive value (NPV) of 99.6 %. For Follow-up: Using a logistic regression with FGFR3 mutation and the CMI at two time points (beginning of the follow-up and current time point), we got sensitivity/specificity/NPV of 90.3 %/65.1 %/97.0 % and a corrected AUC of 0.84. We also tested a thresholding algorithm with FGFR3 mutation and the two time points as described above, obtaining sensitivity/specificity/NPV values of, respectively, 94.5 %/75.9 %/98.5 % and an AUC of 0.82. Conclusions: We showed that combined analysis of FGFR3 mutation and DNA methylation markers

  12. A cadaveric study involving variations in external morphology of gall bladder

    Directory of Open Access Journals (Sweden)

    Anjankar Vaibhav Prakash, Panshewdikar Pradnyesh N, Joshi DS, Anjankar Ashish Prakash

    2013-04-01

    Full Text Available Background: Variations in the pattern of the extra hepatic biliary tract are usual and are commonly encountered during some radiological investigations or in operation theaters. Such Variations of the morphology of Gall bladder have been well documented in the literature for many years but a detail morphological study of variations of the gall bladder and its incidence is very rare. In this era of quick results, increasing use of diagnostic and interventional procedures makes it important to study variations of gall bladder morphology. Most of the interventional procedures in this modern era are done laparoscopically and there is tremendous increase in the number of laparoscopic cholecystectomies. So, sound knowledge of possible variations in morphology of gall bladder is important. Materials and Methods: This study was undertaken on 90 cadaveric liver and gall bladder specimens in terms of length, maximum transverse diameter, shape, external variations of gall bladder, Interior and length of gall bladder below the inferior border of the liver. Results: GB had length ranging between 7 and 10 cm, transverse diameter between 2 and 5 cm. The commonest shape observed in this study was pear shaped in 82.22% of cases. The length of gall bladder below the inferior border of liver varied between 0.4 and 2.5 cm. Conclusion: The growing importance of such variations, lie not only from the point of biliary disease but also with respect to the various invasive techniques in the diagnosis and treatment of gall bladder and extrahepatic bile duct disease.

  13. Stromal modulation of bladder cancer-initiating cells in a subcutaneous tumor model.

    Science.gov (United States)

    Peek, Elizabeth M; Li, David R; Zhang, Hanwei; Kim, Hyun Pyo; Zhang, Baohui; Garraway, Isla P; Chin, Arnold I

    2012-01-01

    The development of new cancer therapeutics would benefit from incorporating efficient tumor models that mimic human disease. We have developed a subcutaneous bladder tumor regeneration system that recapitulates primary human bladder tumor architecture by recombining benign human fetal bladder stromal cells with SW780 bladder carcinoma cells. As a first step, SW780 cells were seeded in ultra low attachment cultures in order to select for sphere-forming cells, the putative cancer stem cell (CSC) phenotype. Spheroids were combined with primary human fetal stromal cells or vehicle control and injected subcutaneously with Matrigel into NSG mice. SW780 bladder tumors that formed in the presence of stroma showed accelerated growth, muscle invasion, epithelial to mesenchymal transition (EMT), decreased differentiation, and greater activation of growth pathways compared to tumors formed in the absence of fetal stroma. Tumors grown with stroma also demonstrated a greater similarity to typical malignant bladder architecture, including the formation of papillary structures. In an effort to determine if cancer cells from primary tumors could form similar structures in vivo using this recombinatorial approach, putative CSCs, sorted based on the CD44(+)CD49f(+) antigenic profile, were collected and recombined with fetal bladder stromal cells and Matrigel prior to subcutaneous implantation. Retrieved grafts contained tumors that exhibited the same structure as the original primary human tumor. Primary bladder tumor regeneration using human fetal bladder stroma may help elucidate the influences of stroma on tumor growth and development, as well as provide an efficient and accessible system for therapeutic testing.

  14. The miR-200 family and miR-205 are repressed by Twist1 and concurrently silenced and DNA hypermethylated in invasive bladder cancer

    DEFF Research Database (Denmark)

    Wiklund, Erik Digman

    invasion and metastasis by negatively regulating the transcriptional repressors of E-cadherin, ZEB1 and ZEB2. Loss of miR-200 expression leads to silencing of E-cadherin, thereby promoting epithelial to mesenchymal transition (EMT) and loss of cell adhesion. However, little is known about...

  15. Robot-assisted laparoscopic augmentation ileocystoplasty in a tubercular bladder

    Directory of Open Access Journals (Sweden)

    Prem Nath Dogra

    2014-01-01

    Full Text Available Some of the patients with genitourinary tuberculosis (GUTB present to the urologist with small contracted bladders or with significant renal damage. [1] Additional reconstructive procedures are often required along with anti-tubercular treatment in these patients. These procedures commonly performed via the open approach, now have the advantage of minimally invasive approach provided by laparoscopic and robotic surgery. The technique of robot-assisted laparoscopic augmentation ileocystoplasty in a patient with a small contracted bladder due to GUTB will be described. The procedure was performed via a completely intra-corporeal technique using an ileal "cap" created from a 15 cm segment of distal ileum which was anastomosed to the urinary bladder bi-valved in the mid-sagittal plane. The procedure lasted for 420 minutes and the patient was discharged on postoperative day 5. At 6 month follow-up, the patient has no irritative urinary symptoms and voiding with insignificant post-void residual urine.

  16. Combined systemic therapy and radiotherapy for bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-12-15

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

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

    Science.gov (United States)

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

    2015-01-01

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

  18. Regulation of nonmuscle myosin II during 3-methylcholanthrene induced dedifferentiation of C2C12 myotubes

    Energy Technology Data Exchange (ETDEWEB)

    Dey, Sumit K.; Saha, Shekhar; Das, Provas; Das, Mahua R.; Jana, Siddhartha S., E-mail: bcssj@iacs.res.in

    2014-08-01

    3-Methylcholanthrene (3MC) induces tumor formation at the site of injection in the hind leg of mice within 110 days. Recent reports reveal that the transformation of normal muscle cells to atypical cells is one of the causes for tumor formation, however the molecular mechanism behind this process is not well understood. Here, we show in an in vitro study that 3MC induces fragmentation of multinucleate myotubes into viable mononucleates. These mononucleates form colonies when they are seeded into soft agar, indicative of cellular transformation. Immunoblot analysis reveals that phosphorylation of myosin regulatory light chain (RLC{sub 20}) is 5.6±0.5 fold reduced in 3MC treated myotubes in comparison to vehicle treated myotubes during the fragmentation of myotubes. In contrast, levels of myogenic factors such as MyoD, Myogenin and cell cycle regulators such as Cyclin D, Cyclin E1 remain unchanged as assessed by real-time PCR array and reverse transcriptase PCR analysis, respectively. Interestingly, addition of the myosin light chain kinase inhibitor, ML-7, enhances the fragmentation, whereas phosphatase inhibitor perturbs the 3MC induced fragmentation of myotubes. These results suggest that decrease in RLC{sub 20} phosphorylation may be associated with the fragmentation step of dedifferentiation. - Highlights: • 3-Methylcholanthrene induces fragmentation of C2C12-myotubes. • Dedifferentiation can be divided into two steps – fragmentation and proliferation. • Fragmentation is associated with rearrangement of nonmuscle myosin II. • Genes associated with differentiation and proliferation are not altered during fragmentation. • Phosphorylation of myosin regulatory light chain is reduced during fragmentation.

  19. Myosin 18A coassembles with nonmuscle myosin 2 to form mixed bipolar filaments.

    Science.gov (United States)

    Billington, Neil; Beach, Jordan R; Heissler, Sarah M; Remmert, Kirsten; Guzik-Lendrum, Stephanie; Nagy, Attila; Takagi, Yasuharu; Shao, Lin; Li, Dong; Yang, Yi; Zhang, Yingfan; Barzik, Melanie; Betzig, Eric; Hammer, John A; Sellers, James R

    2015-03-30

    Class-18 myosins are most closely related to conventional class-2 nonmuscle myosins (NM2). Surprisingly, the purified head domains of Drosophila, mouse, and human myosin 18A (M18A) lack actin-activated ATPase activity and the ability to translocate actin filaments, suggesting that the functions of M18A in vivo do not depend on intrinsic motor activity. M18A has the longest coiled coil of any myosin outside of the class-2 myosins, suggesting that it might form bipolar filaments similar to conventional myosins. To address this possibility, we expressed and purified full-length mouse M18A using the baculovirus/Sf9 system. M18A did not form large bipolar filaments under any of the conditions tested. Instead, M18A formed an ∼ 65-nm-long bipolar structure with two heads at each end. Importantly, when NM2 was polymerized in the presence of M18A, the two myosins formed mixed bipolar filaments, as evidenced by cosedimentation, electron microscopy, and single-molecule imaging. Moreover, super-resolution imaging of NM2 and M18A using fluorescently tagged proteins and immunostaining of endogenous proteins showed that NM2 and M18A are present together within individual filaments inside living cells. Together, our in vitro and live-cell imaging data argue strongly that M18A coassembles with NM2 into mixed bipolar filaments. M18A could regulate the biophysical properties of these filaments and, by virtue of its extra N- and C-terminal domains, determine the localization and/or molecular interactions of the filaments. Given the numerous, fundamental cellular and developmental roles attributed to NM2, our results have far-reaching biological implications.

  20. Non-muscle Myosin II Isoforms Co-assemble in Living Cells

    Science.gov (United States)

    Beach, Jordan R.; Shao, Lin; Remmert, Kirsten; Li, Dong; Betzig, Eric; Hammer, John A.

    2014-01-01

    SUMMARY Non-muscle myosin II (NM II) powers myriad developmental and cellular processes, including embryogenesis, cell migration, and cytokinesis [1]. To exert its functions, monomers of NM II assemble into bipolar filaments that produce a contractile force on the actin cytoskeleton. Mammalian cells express up to three isoforms of NM II (NM IIA, IIB and IIC), each of which possesses distinct biophysical properties and supports unique, as well as redundant, cellular functions [2-8]. Despite previous efforts [9-13], it remains unclear if NM II isoforms assemble in living cells to produce mixed (heterotypic) bipolar filaments, or if filaments consist entirely of a single isoform (homotypic). We addressed this question using fluorescently-tagged versions of NM IIA, IIB and IIC, isoform-specific immunostaining of the endogenous proteins, and two-color total internal reflection fluorescence structured-illumination microscopy, or TIRF-SIM, to visualize individual myosin II bipolar filaments inside cells. We show that NM II isoforms co-assemble into heterotypic filaments in a variety of settings, including various types of stress fibers, individual filaments throughout the cell, and the contractile ring. We also show that the differential distribution of NM IIA and NM IIB typically seen in confocal micrographs of well-polarized cells is reflected in the composition of individual bipolar filaments. Interestingly, this differential distribution is less pronounced in freshly-spread cells, arguing for the existence of sorting mechanism acting over time. Together, our work argues that individual NM II isoforms are potentially performing both isoform-specific and isoform-redundant functions while co-assembled with other NM II isoforms. PMID:24814144

  1. Glucocorticosteroid-sensitive inflammatory eosinophilic pseudotumor of the bladder in an adolescent: a case report

    Directory of Open Access Journals (Sweden)

    Qu Chuangyu

    2009-11-01

    Full Text Available Abstract Introduction Inflammatory eosinophilic pseudotumor of the bladder is a rare inflammatory bladder disease. The etiology and pathophysiology of this condition are still unclear. Few case reports have described inflammatory eosinophilic pseudotumor of the bladder in adults or children. Although benign, this disease is occasionally clinically aggressive and locally invasive, thus open surgical removal or complete transurethral resection is recommended. Case presentation We present the case of a biopsy-proven inflammatory eosinophilic pseudotumor of the bladder in a previously healthy 16-year-old male adolescent with 2-month history of frequent micturition and dysuria with no significant apparent causative factors. The tumor regressed after a 6-week course of glucocorticosteroids. Conclusion To the best of our knowledge, our case is a rare case of inflammatory eosinophilic pseudotumor of the bladder treated with complete conservative management. Due to its glucocorticosteroid-sensitive nature, we postulate that this disease belongs to a subgroup of eosinophilic disorders.

  2. Species Differences in the Distribution of the Nonmuscle Myosin Heavy Chain IIB Inserted Isoform in the Brain(Biochemistry)

    OpenAIRE

    Shin-ya, Hagiwara; MASAYUKI, TAKAHASHI; Akihiko, Yamagishi; Division of Biological Sciences, Graduate School of Science, Hokkaido University

    2001-01-01

    The alternatively spliced isoform of the nonmuscle myosin heavy chain IIB (MHC-IIB) with an insert of 21 amino acids near the actin-binding region, MHC-IIB (B2), is expressed specifically in the brain and spinal cord in Mammalia and Aves. We performed immunoblot analyses to elucidate the distribution of MHC-IIB (B2) in the brains of various animals. Nearly half of MHC-IIB existed as the B2 inserted isoform (MHC-IIB (B2)) in the cerebrum of the guinea-pig, rabbit and pig, while the non-B2 inse...

  3. Species Differences in the Distribution of the Nonmuscle Myosin Heavy Chain IIB Inserted Isoform in the Brain

    OpenAIRE

    Hagiwara, Shin-ya; Takahashi, Masayuki; Yamagishi, Akihiko

    2001-01-01

    The alternatively spliced isoform of the nonmuscle myosin heavy chain IIB (MHC-IIB) with an insert of 21 amino acids near the actin-binding region, MHC-IIB(B2), is expressed specifically in the brain and spinal cord in Mammalia and Aves. We performed immunoblot analyses to elucidate the distribution of MHC-IIB(B2) in the brains of various animals. Nearly half of MHC-IIB existed as the B2 inserted isoform (MHC-IIB(B2)) in the cerebrum of the guinea-pig, rabbit and pig, while the non-B2 inserte...

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

    Science.gov (United States)

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

    2011-03-07

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

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

    Directory of Open Access Journals (Sweden)

    Shengjie Guo

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

  6. PROGNOSTIC SIGNIFICANCE OF KI-67, MMP-9 AND COL IV IMMUNOHISTOCHEMICAL MARKERS AT BLADDER TUMORS

    Directory of Open Access Journals (Sweden)

    V. P. Avdoshin

    2011-01-01

    Full Text Available The prognostic value of the expression Ki-67, ММР-9 and collagen IV were estimated in urotelial bladder tumors. The biopsy and surgery samples from 43 patients (27 males and 16 females aged 42 to 87 years (mean age 66 ± 1.5 years who received combination treatment for urotelial tumors. It has been found that Ki-67, ММР-9 and collagen IV are important prognostic markers of urotelial invasive bladder carcinoma.

  7. Inhibition of bladder overactivity by a combination of tibial neuromodulation and tramadol treatment in cats

    Science.gov (United States)

    Zhang, Fan; Mally, Abhijith D.; Ogagan, P. Dafe; Shen, Bing; Wang, Jicheng; Roppolo, James R.; de Groat, William C.

    2012-01-01

    Our recent study in cats revealed that inhibition of bladder overactivity by tibial nerve stimulation (TNS) depends on the activation of opioid receptors. TNS is a minimally invasive treatment for overactive bladder (OAB), but its efficacy is low. Tramadol (an opioid receptor agonist) is effective in treating OAB but elicits significant adverse effects. This study was to determine if a low dose of tramadol (expected to produce fewer adverse effects) can enhance the TNS inhibition of bladder overactivity. Bladder overactivity was induced in α-chloralose-anesthetized cats by an intravesical infusion of 0.25% acetic acid (AA) during repeated cystometrograms (CMGs). TNS (5 Hz) at two to four times the threshold intensity for inducing toe movement was applied during CMGs before and after tramadol (0.3–7 mg/kg iv) to examine the interaction between the two treatments. AA irritation significantly reduced bladder capacity to 24.8 ± 3.3% of the capacity measured during saline infusion. TNS alone reversibly inhibited bladder overactivity and significantly increased bladder capacity to 50–60% of the saline control capacity. Tramadol administered alone in low doses (0.3–1 mg/kg) did not significantly change bladder capacity, whereas larger doses (3–7 mg/kg) increased bladder capacity (50–60%). TNS in combination with tramadol (3–7 mg/kg) completely reversed the effect of AA. Tramadol also unmasked a prolonged (>2 h) TNS inhibition of bladder overactivity that persisted after termination of the stimulation. The results suggest a novel treatment strategy for OAB by combining tibial neuromodulation with a low dose of tramadol, which is minimally invasive with a potentially high efficacy and fewer adverse effects. PMID:22496406

  8. Permeability and ultrastructure of human bladder epithelium

    DEFF Research Database (Denmark)

    Eldrup, J; Thorup, Jørgen Mogens; Nielsen, S L;

    1983-01-01

    Leakage of tight junctions as observed with electron microscopy and demonstration of solute transport across bladder epithelium was investigated in 13 patients with different bladder diseases: urinary retention and infection, bladder tumours and interstitial cystitis. The latter group showed cons...

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

    Directory of Open Access Journals (Sweden)

    Carmen J Marsit

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

  10. CT findings of primary localized amyloidosis of the urinary bladder: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Hwan; Kim, See Hyung; Kim, Mi Jeong; Kim, Sang Pyo [Keimyung Univ. College of Medicine/Dongsan Hospital, Daegu (Korea, Republic of)

    2012-08-15

    Primary localized amyloidosis is a rare disease that impairs the organs and tissue function, caused by extracellular deposition of amyloid protein. Although amyloid proteins can be deposited in localized or systemic organs, the bladder is a rare site. CT showed diffuse infiltrative mass in the left urinary bladder wall, and the left ureterovesical junction with enhancement and perivesical invasion, which mimics urothelial carcinoma. However, pathological diagnosis was localized primary amyloidosis. We report here on the CT findings of a rare case of primary localized amyloidosis of the urinary bladder with brief review of the literature.

  11. Laparoscopic repair in children with traumatic bladder perforation.

    Science.gov (United States)

    Karadag, Cetin Ali; Tander, Burak; Erginel, Basak; Demirel, Dilek; Bicakci, Unal; Gunaydin, Mithat; Sever, Nihat; Bernay, Ferit; Dokucu, Ali Ihsan

    2016-01-01

    Here, we report two patients with a traumatic intraperitoneal bladder dome rupture repaired by laparoscopic intracorporeal sutures. The first patient was a 3-year old boy was admitted with a history of road accident. He had a traumatic lesion on his lower abdomen and a pelvic fracture. Computed tomography (CT) scan revealed free intraabdominal fluid. The urethragram showed spreading contrast material into the abdominal cavity. Laparoscopic exploration revealed a 3-cm-length perforation at the top of the bladder. The injury was repaired in a two fold fashion. Post-operative follow-up was uneventful. The second case was a 3-year-old boy fell from the second floor of his house on the ground. He had traumatic lesion on his lower abdomen and a pelvic fracture. Due to bloody urine drainage, a cystography was performed and an extravasation from the dome of the bladder into the peritoneum was detected. On laparoscopy, a 3-cm long vertical perforation at the dome of the bladder was found. The perforation was repaired in two layers with intracorporeal suture technique. The post-operative course was uneventful. Laparoscopic repair of traumatic perforation of the bladder dome is a safe, effective and minimally invasive method. The cosmetic outcome is superior.

  12. Laparoscopic repair in children with traumatic bladder perforation

    Directory of Open Access Journals (Sweden)

    Cetin Ali Karadag

    2016-01-01

    Full Text Available Here, we report two patients with a traumatic intraperitoneal bladder dome rupture repaired by laparoscopic intracorporeal sutures. The first patient was a 3-year old boy was admitted with a history of road accident. He had a traumatic lesion on his lower abdomen and a pelvic fracture. Computed tomography (CT scan revealed free intraabdominal fluid. The urethragram showed spreading contrast material into the abdominal cavity. Laparoscopic exploration revealed a 3-cm-length perforation at the top of the bladder. The injury was repaired in a two fold fashion. Post-operative follow-up was uneventful. The second case was a 3-year-old boy fell from the second floor of his house on the ground. He had traumatic lesion on his lower abdomen and a pelvic fracture. Due to bloody urine drainage, a cystography was performed and an extravasation from the dome of the bladder into the peritoneum was detected. On laparoscopy, a 3-cm long vertical perforation at the dome of the bladder was found. The perforation was repaired in two layers with intracorporeal suture technique. The post-operative course was uneventful. Laparoscopic repair of traumatic perforation of the bladder dome is a safe, effective and minimally invasive method. The cosmetic outcome is superior.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-10-15

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

  14. Relationship between FISH test of hematuria exfaliated cells and tumor myametrial invasion in patients with suspected bladder cancer%FISH检测尿脱落细胞的临床意义及与肿瘤肌层浸润的关系

    Institute of Scientific and Technical Information of China (English)

    许洁; 张芬; 张明辉; 李丽; 庄恒国; 刘艳辉; 赵彤

    2011-01-01

    sensitivity of FISH was higher in muscle-invasive cases (88.24%) than that in non-muscle-invasive cases (53.85% ),and both were higher than that in cytologic examination( 15.38%, 35.29% ).All of these difference had significantly statistical value (P<0.05).The aberration ratio in chromosomes 3, 7, 9, 17 was 88.34%,64.71%, 70.59% and 88.24%, respectively.The abberant of chromosomes 3 and 17 related to the tumor invasion, and the degree of the aberration positively related to the decpth of tumor invasion (rp = 0.591, P < 0.05; rp = 0.523, P < 0.05).Conclusions FISH has higher sensitivity and specificity for the detection of bladder tumors than that of cytologic examination, especially for those with muscle invasion.In addition, chromosomes 3 and 17 abnormalities are correlated to the deepth of invasion.

  15. A pilot study on bladder wall thickness at different filling stages

    Science.gov (United States)

    Zhang, Xi; Liu, Yang; Li, Baojuan; Zhang, Guopeng; Liang, Zhengrong; Lu, Hongbing

    2015-03-01

    The ever-growing death rate and the high recurrence of bladder cancer make the early detection and appropriate followup procedure of bladder cancer attract more attention. Compare to optical cystoscopy, image-based studies have revealed its potentials in non-invasive observations of the abnormities of bladder recently, in which MR imaging turns out to be a better choice for bladder evaluation due to its non-ionizing and high contrast between urine and wall tissue. Recent studies indicate that bladder wall thickness tends to be a good indicator for detecting bladder wall abnormalities. However, it is difficult to quantitatively compare wall thickness of the same subject at different filling stages or among different subjects. In order to explore thickness variations at different bladder filling stages, in this study, we preliminarily investigate the relationship between bladder wall thickness and bladder volume based on a MRI database composed of 40 datasets acquired from 10 subjects at different filling stages, using a pipeline for thickness measurement and analysis proposed in our previous work. The Student's t-test indicated that there was no significant different on wall thickness between the male group and the female group. The Pearson correlation analysis result indicated that negative correlation with a correlation coefficient of -0.8517 existed between the wall thickness and bladder volume, and the correlation was significant(p score of wall thickness would be more appropriate to reflect the thickness variations. For possible abnormality detection of a bladder based on wall thickness, the intra-subject and inter-subject thickness variation should be considered.

  16. The use of cystometry in small rodents: a study of bladder chemosensation.

    Science.gov (United States)

    Uvin, Pieter; Everaerts, Wouter; Pinto, Silvia; Alpízar, Yeranddy A; Boudes, Mathieu; Gevaert, Thomas; Voets, Thomas; Nilius, Bernd; Talavera, Karel; De Ridder, Dirk

    2012-08-21

    The lower urinary tract (LUT) functions as a dynamic reservoir that is able to store urine and to efficiently expel it at a convenient time. While storing urine, however, the bladder is exposed for prolonged periods to waste products. By acting as a tight barrier, the epithelial lining of the LUT, the urothelium, avoids re-absorption of harmful substances. Moreover, noxious chemicals stimulate the bladder's nociceptive innervation and initiate voiding contractions that expel the bladder's contents. Interestingly, the bladder's sensitivity to noxious chemicals has been used successfully in clinical practice, by intravesically infusing the TRPV1 agonist capsaicin to treat neurogenic bladder overactivity. This underscores the advantage of viewing the bladder as a chemosensory organ and prompts for further clinical research. However, ethical issues severely limit the possibilities to perform, in human subjects, the invasive measurements that are necessary to unravel the molecular bases of LUT clinical pharmacology. A way to overcome this limitation is the use of several animal models. Here we describe the implementation of cystometry in mice and rats, a technique that allows measuring the intravesical pressure in conditions of controlled bladder perfusion. After laparotomy, a catheter is implanted in the bladder dome and tunneled subcutaneously to the interscapular region. Then the bladder can be filled at a controlled rate, while the urethra is left free for micturition. During the repetitive cycles of filling and voiding, intravesical pressure can be measured via the implanted catheter. As such, the pressure changes can be quantified and analyzed. Moreover, simultaneous measurement of the voided volume allows distinguishing voiding contractions from non-voiding contractions. Importantly, due to the differences in micturition control between rodents and humans, cystometric measurements in these animals have only limited translational value. Nevertheless, they are

  17. Evidence for Bladder Urothelial Pathophysiology in Functional Bladder Disorders

    Directory of Open Access Journals (Sweden)

    Susan K. Keay

    2014-01-01

    Full Text Available Understanding of the role of urothelium in regulating bladder function is continuing to evolve. While the urothelium is thought to function primarily as a barrier for preventing injurious substances and microorganisms from gaining access to bladder stroma and upper urinary tract, studies indicate it may also function in cell signaling events relating to voiding function. This review highlights urothelial abnormalities in bladder pain syndrome/interstitial cystitis (BPS/IC, feline interstitial cystitis (FIC, and nonneurogenic idiopathic overactive bladder (OAB. These bladder conditions are typified by lower urinary tract symptoms including urinary frequency, urgency, urgency incontinence, nocturia, and bladder discomfort or pain. Urothelial tissues and cells from affected clinical subjects and asymptomatic controls have been compared for expression of proteins and mRNA. Animal models have also been used to probe urothelial responses to injuries of the urothelium, urethra, or central nervous system, and transgenic techniques are being used to test specific urothelial abnormalities on bladder function. BPS/IC, FIC, and OAB appear to share some common pathophysiology including increased purinergic, TRPV1, and muscarinic signaling, increased urothelial permeability, and aberrant urothelial differentiation. One challenge is to determine which of several abnormally regulated signaling pathways is most important for mediating bladder dysfunction in these syndromes, with a goal of treating these conditions by targeting specific pathophysiology.

  18. Effects of electrotherapy in treatment of neurogenic bladder in children with occult spinal dysraphism

    Directory of Open Access Journals (Sweden)

    Ćirović Dragana

    2009-01-01

    Full Text Available Introduction Neurogenic bladder can develop as a result of various degrees of neurogenic lesion in spina bifida. The degree of bladder dysfunction depends on the level and type of spina bifida. Due to results upon complete diagnostic protocols, treatment options are applied. Objective Comparison of therapy results of patients with occult spinal dysraphism with neurogenic bladder that under-went medicamentous therapy and medicamentous with electrotherapy treatment. Methods We had 49 patients with neurogenic bladder that were treated at the University Children's Hospital in Belgrade in the period 2003-2008. The first group of children received medicamentous therapy and the second group received medicamentous therapy with transcutaneous electric nerve stimulation. In both groups we evaluated 4 symptoms: daily enuresis, enuresis nocturna, urgency and frequency and 4 urodynamic parameters: lower bladder capacity, unstable contractions and residual urine and detrusor sphincter dyssynergia. Follow-up urodynamic evaluation was done after 3, 6 and 12 months respectively. Results Our findings pointed out a high statistical significance of improvement in all evaluated urodynamic parameters of neurogenic bladder (predominantly in bladder capacity in the group of children with combined therapy as well in resolution of symptoms (predominantly enuresis nocturna, urgency and frequency. Conclusion Combined therapy is more efficient in treatment of children with neurogenic bladder. Electrotherapy is non-invasive, easily applicable and has had a significant place in treatment of children with dysfunctional voiding.

  19. Prognostic significance of the 2004 WHO classification compared with the 1973 WHO classification for organ-confined invasive bladder cancer%2004年和1973年世界卫生组织肿瘤分级预测局限浸润性膀胱癌复发价值的比较

    Institute of Scientific and Technical Information of China (English)

    钟明珠; 郭胜杰; 蒋丽娟; 云径平; 周芳坚

    2013-01-01

    Objective To compare the 2004 and 1973 WHO classifications for predicting tumor recurrence for organ-confined (T stage ≤ pT2b) invasive urothelial carcinoma of the bladder treated with radical cystectomy.Methods From February 2000 to August 2011,the 173 consecutive cases of organconfined invasive urothelial carcinoma of the bladder were treated with radical cystectomy.The data of clinical and follow-up information was collected.The KapIan-Meier plots with Log-rank test were used to estimate recurrence-free survival (RFS).Univariate and multivariate analysis using the Cox proportional hazard regression model were performed to evaluate the impact of any clinicopathological prognostic factors (tumor grade,tumor stage,lymph node status,lymphovascular invasion,preoperative hydronephrosis,and non-pure urothelial carcinoma) on RFS.Results The 5-year RFS was 84.7% for the entire cohort.Univariate and multivariate analysis demonstrated that when using the 2004 WHO classification,lymph node status (RR =4.573,95% CI:1.469-14.237),tumor grade (RR =9.993,95% CI:1.325-75.390) and preoperative hydronephrosis (RR =3.207,95% CI:1.209-8.508) presented independent predictors for RFS; while using the 1973 WHO system,lymph node status (RR =9.484,95% CI:3.450-26.074) and lymphovascular invasion (RR =3.009,95% CI:1.062-8.526) were independent predictors.Conclusions The 2004 WHO classification,as an independent factor,is superior to the 1973 classification for predicting RFS in patients with organ-confined invasive bladder cancer treated with radical cystectomy.However,a further perspective study is needed to validate its role in prognosis.%目的 比较2004年和1973年WHO肿瘤分级预测局限浸润性(T分期≤pT2b)膀胱尿路上皮癌行根治性膀胱切除术后肿瘤复发概率的价值.方法 回顾分析2000年2月至2011年8月具有完善随访结果的173例局限浸润性膀胱尿路上皮癌患者的临床及随访资料.采用Kaplan-Meier法和Log-rank

  20. Postmortem MRI of bladder agenesis

    Energy Technology Data Exchange (ETDEWEB)

    Barber, Brendan R. [St George' s Hospital, Radiology Department, London (United Kingdom); Weber, Martin A. [Great Ormond Street Hospital for Children, Department of Histopathology, London (United Kingdom); Bockenhauer, Detlef [Great Ormond Street Hospital for Children, Department of Nephrology, London (United Kingdom); Hiorns, Melanie P.; McHugh, Kieran [Great Ormond Street Hospital for Children, Radiology Department, London (United Kingdom)

    2011-01-15

    We report a 35-week preterm neonate with bladder agenesis and bilateral dysplastic kidneys. A suprapubic catheter was inadvertently inserted into one of the larger inferior cysts of the left dysplastic kidney. A postmortem MRI scan was performed with the findings being confirmed on autopsy. We are unaware of another postmortem MRI study demonstrating bladder agenesis. (orig.)

  1. Molecular Diagnosis in Bladder Cancer

    NARCIS (Netherlands)

    T.C.M. Zuiverloon (Tahlita)

    2013-01-01

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

  2. Genetics Home Reference: bladder cancer

    Science.gov (United States)

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

  3. 中国人同期行经尿道膀胱肿瘤电切术和经尿道前列腺电切术对膀胱癌复发影响的meta分析%Recurrence of Simultaneous TUR - BT and TUR - P for Non - muscle Invasive Bladder Cancer Complicated with Prostatic Hyperplasia in Chinese People: meta - analysis

    Institute of Scientific and Technical Information of China (English)

    李嘉; 吴斌

    2011-01-01

    目的 利用meta分析探讨中国人同期行经尿道膀胱肿瘤电切术(TUR - BT)和经尿道前列腺电切术(TUR - P)治疗非肌层浸润性膀胱癌合并前列腺增生症与单纯行经尿道膀胱肿瘤电切术对肿瘤复发的影响.方法 利用中国期刊全文数据库、Medline检索2010年1月以前的中国人群中同期行TUR - BT和TUR -P术(A组)治疗非肌层浸润性膀胱癌合并前列腺增生症与单纯行TUR - BT术(B组)对肿瘤复发的影响进行比较的病例对照研究.根据纳入和排除标准,筛选符合的文献.应用Revman 4.2软件,对纳入的文献进行meta分析,并进行发表偏倚估计和敏感性分析.结果 符合纳入标准的文献共4篇,总样本量为218例,其中A组110例,复发38例;B组108例,复发43例.合并OR(95% CI)值为0.76(0.43,1.34).所有病例均未发现前列腺窝处的复发和转移.结论 关于同期行TUR - BT和TUR -P术和单纯行TUR - BT术对肿瘤的复发率的影响,合并OR(95% CI)值为0.76(0.43,1.34),森林图的菱形标记位于“1”的两侧,说明同期行TUR - BT和TUR -P术对于膀胱肿瘤的复发的影响既不是保护因素,也不是危险因素,既不能认为同期行TUR - BT和TUR -P术可以增加或减少膀胱肿瘤的复发率.%Abstract Objective To investigate the recurrence of simultaneous TUR - BT and TUR - P for non - muscle invasive bladder cancer complicated with prostatic hyperplasia in Chinese people by meta - analysis. Methods We retrieved all the case - controlled studies on the comparison of tumor recurrence of simultaneous TUR - BT and TUR - P( group A) and TUR - BT alone( group B) to treat non - muscle invasive bladder cancer complicated with benign prostatic hyperplasia by searching Medline and Chinese Journal Full - text Database ( CJFD) ( up to January 2010) .screened the eligible literature according to the selection and exclusion criteria,and performed meta - ana-lyses on the included studies using the Revman 4. 2

  4. Metastasis-associated protein Mts1 (S100A4) inhibits CK2-mediated phosphorylation and self-assembly of the heavy chain of nonmuscle myosin

    DEFF Research Database (Denmark)

    Kriajevska, M; Bronstein, I B; Scott, D J

    2000-01-01

    A role for EF-hand calcium-binding protein Mts1 (S100A4) in the phosphorylation and the assembly of myosin filaments was studied. The nonmuscle myosin molecules form bipolar filaments, which interact with actin filaments to produce a contractile force. Phosphorylation of the myosin plays...

  5. Expression of Hpa and CD222 in bladder carcinoma and analysis of clinico-pathologic correlation

    Institute of Scientific and Technical Information of China (English)

    Shuhong Shi; Hui Zhang

    2014-01-01

    Objective:Our study aimed to investigate the relationships between the clinico-pathologic features and the hepa-ranase (Hpa) and CD222 expressions in bladder carcinoma. Methods:The expressions of Hpa and CD222 in 95 bladder carcinoma specimens and 20 paraneoplastic bladder tissues (controls) were assessed using the immunohistochemical stain-ing method. Results:The positive expression rates of Hpa and CD222 in bladder carcinoma were 68.42%and 61.05%, respectively. The positive rate of Hpa was significantly higher in the carcinoma specimens than in the control specimens (P<0.01). Similarly, the Hpa expression in the invasive bladder carcinoma was significantly higher than that in the non-invasive bladder carcinoma (P<0.01). A positive correlation was observed between the expressions of Hpa and CD222 (P<0.05). The expressions of Hpa and CD222 were significantly correlated with lymphatic invasion and TNM staging (P<0.05). The 5-year survival rate was significantly higher in negative expression of the Hpa group than that in the positive expression group (P<0.05). Compared with the non-co-positive expression group, the 5-year survival rate in the co-positive expression of Hpa and CD222 group was significantly lower (P<0.05). Conclusion:High Hpa and CD222 expressions in tumor tissues were associated with the occurrence and development of bladder carcinoma. Our results provide helpful information for the further diagnosis and therapy of bladder carcinoma.

  6. Simple cyst of urinary bladder.

    Science.gov (United States)

    Bo, Yang

    2014-07-01

    Simple cysts are rare in the urinary bladder and can pose a diagnostic dilemma to both the urologist and the histopathologist. No case study was found in the database of Elsevier Science Direct, Spring-Link, or PubMed. We present two cases of subserous cyst in the bladder and discuss the diagnosis and treatment of the condition. The cystic lesion at bladder dome was detected by radiologic examination and confirmed by cystoscopy. In case 1, transurethral resection was first performed which was followed by partial cystectomy; In case 2, the cyst was removed with the urachus using laparoscopic surgery. The patients recovered uneventfully and the histopathology showed cysts in subserous layer of urinary bladder. The bladder cyst should be distinguished from urachal tumor, and laparoscopic partial cystectomy is the preferred operative procedure.

  7. Emerging Immunotargets in Bladder Cancer.

    Science.gov (United States)

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

    2016-01-01

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

  8. Increased bladder wall thickness is associated with severe symptoms and reduced bladder capacity in patients with bladder pain syndrome

    Directory of Open Access Journals (Sweden)

    Shu-Yu Wu

    2016-12-01

    Conclusion: There are obvious differences in bladder CT scans of patients with symptoms of bladder pain due to different etiology. Increased BWT was associated with increased pain scores and decreased bladder capacity in patients with KC and IC. BWT on a CT scan might be considered a marker for the severity of bladder inflammation.

  9. Diagnosis of Bladder Cancer Recurrence Based on Urinary Levels of EOMES, HOXA9, POU4F2, TWIST1, VIM, and ZNF154 Hypermethylation

    DEFF Research Database (Denmark)

    Reinert, Thomas; Borre, Michael; Christiansen, Anders;

    2012-01-01

    Non muscle invasive bladder cancer (NMIBC) has the highest recurrence rate of any malignancy and as many as 70% of patients experience relapse. Aberrant DNA methylation is present in all bladder tumors and can be detected in urine specimens. Previous studies have identified DNA methylation marker...

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

    Science.gov (United States)

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

    2017-05-01

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

  11. [Sacral neuromodulation for neurogenic bladder dysfunction].

    Science.gov (United States)

    Kessler, T M; Wöllner, J; Kozomara, M; Mordasini, L; Mehnert, U

    2012-02-01

    Sacral neuromodulation (SNM) represents a promising option for managing treatment-refractory neurogenic bladder dysfunction. It remains to be seen, however, which types of neurogenic bladder dysfunction and which underlying neurological disorders best respond to SNM. Constant improvements in SNM have been achieved and it is now a minimally invasive approach performed under local anesthesia which should be considered before undertaking larger reconstructive procedures. An electrode is implanted in the S3 or S4 sacral foramen and during a test phase lasting for days to weeks the patient keeps a bladder diary to determine whether SNM has provided a relevant benefit. If the results of the test phase are positive, a neuromodulator is implanted in the gluteal area (or more rarely in the abdominal wall).The mechanism of action of SNM has not been completely clarified, but the afferent nerves most likely play a key role. It appears that SNM produces a modulation of medullary reflexes and brain centers by peripheral afferents. The implanted neuromodulation system does not lead to limitation of the patient's activities. However, it should be noted that high-frequency diathermy and unipolar electrocauterization are contraindicated in patients with neuromodulators, that during extracorporeal shock wave lithotripsy the focal point should not be in the direct vicinity of the neuromodulator or the electrode, that ultrasound and radiotherapy in the region of the implanted components should be avoided, that the neuromodulation should be discontinued in pregnancy, and that MRI examinations should only be conducted when urgently indicated and the neuromodulator is turned off.

  12. Chemoprevention of bladder cancer.

    Science.gov (United States)

    Kamat, Ashish M; Lamm, Donald L

    2002-02-01

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

  13. 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.

  14. A murine model for bladder cancer.

    Science.gov (United States)

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

    1984-01-01

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

  15. Incidental Dose to Pelvic Nodes in Bladder-Only Radiotherapy: Is It Clinically Relevant?

    Science.gov (United States)

    Lewis, Shirley; Murthy, Vedang; Mahantshetty, Umesh; Shrivastava, Shyam Kishore

    2017-06-01

    Although there is a strong biological rationale to electively treat the pelvic nodes during bladder preservation, its clinical benefit is uncertain. This may be explained by the incidental dose received by the nodal regions when treating the bladder alone. This study was conducted to investigate the doses received by the different pelvic nodal regions when the bladder alone is treated by standard conformal radiotherapy. The computed tomography data sets of 20 patients with node-negative muscle-invasive bladder cancer treated in a bladder preservation protocol were studied. Patients were originally treated with conformal radiotherapy to the bladder alone. Replanning was done with additional delineation of the pelvic nodal regions namely common iliac (upper and lower), presacral, internal iliac, obturator, and external iliac. Dose volume parameters such as Dmean, Dmax, D100%, D66%, D33%, V40, and V50 to each of the nodal regions were estimated for all patients. The obturator nodes received the highest dose among all nodal regions. The mean dose received by obturator, external iliac, and internal iliac regions was 59, 45, and 36 Gy, respectively. The dose received by these 3 regions in the full bladder state was 63, 52, and 47 Gy, respectively. The dose received by all other pelvic nodal regions was low and not clinically relevant. The incidental dose received by obturator and external iliac nodes is clinically significant in bladder-only radiation, possibly enough to influence micrometastatic disease. This may be a reason for the lack of clear benefit seen with nodal irradiation in bladder cancer. Advances in Knowledge: This study highlights that the incidental dose received by obturator and external iliac nodes is clinically significant in bladder-only radiation. The obturator nodes received the highest dose among all nodal regions with mean dose of 59 Gy.

  16. Bladder Dysfunction and Urinary Incontinence

    Directory of Open Access Journals (Sweden)

    F. faizi

    2009-01-01

    Full Text Available   "nIn the name of God. Dear colleagues, ladies and gentlemen, it is a great honor to be here. Bladder dysfunction is serious enough to seek serious help. If you may know I am working in a private clinic which it is impossible to follow the patients so this lecture is based on unusual and rare cases who came to me. Bladder dysfunction (BD is common among 30% of young and old people who are suffering from it, however it is more common in old ages. According to a research, women are more involved as in men which prostate has a role is more common. The usual cases were: "n1. A young girl, aged 20, who had to wake up five times during the night to micturate. "n2. Also a lady said when I roll in bed I wet myself. "n3. A young lady who always had to use a pad. "n4. A man said I can’t use underground. "n5. I cannot go out since I have to micturate every hour. "n6. One said I have to wake up every hour at night. "n7. Young people say we have to micturate 3-4 times at night. "n8. A young man said as soon as I feel to micturate I empty my bladder before I’ve reached the WC and I wet myself to the ankle, how could I have a job? "n9. Some women wet themselves when they cough. "nIn order to know and diagnosis, the physiology of bladder function must be known. "nThe bladder is divided into two parts: "nThe Dom, which is innervated by Beta-Adrenergic. It relaxes the bladder in order to comply the urine. "nFrom the orifice of the urether and posterior ridge of the trigon to the bladder neck or internal sphincter. The prostatic urethra plays a major role in conti- nence. It has two parts,   "n1: From the bladder neck to V.M. this is enclaved by extension of detrusor muscles like a sleeve. These muscles contract during ejaculation to prevent retrograde ejaculation. "nDistal urethra from V.M. to the external sphincter which is covered by voluntary muscles. "nThe internal pressure of the urethra is higher than the bladder. If the pressure of the bladder rises

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-04-15

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

  18. Bladder diverticulitis: a case report.

    Science.gov (United States)

    Silberman, Michael; Jeanmonod, Rebecca

    2011-01-01

    Bladder diverticulum, an outpouching of the mucosa through the muscular wall of the bladder, is a multifactorial disease process that can be either acquired or congenital. Although small diverticuli are usually asymptomatic, a large diverticulum may result in hematuria, urinary tract infection, acute abdomen due to its rupture, acute urinary retention, or neoplasm formation. We describe the case of an elderly gentleman who presented to the emergency department with abdominal pain and was ultimately diagnosed with bladder diverticulitis, a disease not previously described in the literature.

  19. Bladder Diverticulitis: A Case Report

    Directory of Open Access Journals (Sweden)

    Michael Silberman

    2011-01-01

    Full Text Available Bladder diverticulum, an outpouching of the mucosa through the muscular wall of the bladder, is a multifactorial disease process that can be either acquired or congenital. Although small diverticuli are usually asymptomatic, a large diverticulum may result in hematuria, urinary tract infection, acute abdomen due to its rupture, acute urinary retention, or neoplasm formation. We describe the case of an elderly gentleman who presented to the emergency department with abdominal pain and was ultimately diagnosed with bladder diverticulitis, a disease not previously described in the literature.

  20. Underactive Bladder in Older Adults.

    Science.gov (United States)

    Chuang, Yao-Chi; Plata, Mauricio; Lamb, Laura E; Chancellor, Michael B

    2015-11-01

    Overactive bladder is one of the most common bladder problems, but an estimated 20 million Americans ha