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Sample records for human bladder urothelium

  1. Correlation between Urothelial Differentiation and Sensory Proteins P2X3, P2X5, TRPV1, and TRPV4 in Normal Urothelium and Papillary Carcinoma of Human Bladder

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    Igor Sterle

    2014-01-01

    Full Text Available Terminal differentiation of urothelium is a prerequisite for blood-urine barrier formation and enables normal sensory function of the urinary bladder. In this study, urothelial differentiation of normal human urothelium and of low and high grade papillary urothelial carcinomas was correlated with the expression and localization of purinergic receptors (P2X3, and P2X5 and transient receptor potential vanilloid channels (TRPV1, and TRPV4. Western blotting and immunofluorescence of uroplakins together with scanning electron microscopy of urothelial apical surface demonstrated terminal differentiation of normal urothelium, partial differentiation of low grade carcinoma, and poor differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium as well as in low grade carcinoma and in both cases immunolabeling was stronger in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5 expression was detected in normal urothelium and in high grade carcinoma, while in low grade carcinoma its expression was diminished. The expression of TRPV1 decreased in low grade and even more in high grade carcinoma when compared with normal urothelium, while TRPV4 expression was unchanged in all samples. Our results suggest that sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns.

  2. Heterogeneity of uroplakin localization in human normal urothelium, papilloma and papillary carcinoma

    International Nuclear Information System (INIS)

    Zupancic, Dasa; Romih, Rok

    2013-01-01

    Uroplakins are differentiation-related membrane proteins of urothelium. We compared uroplakin expression and ultrastructural localization in human normal urothelium, papilloma and papillary carcinoma. Because of high recurrence rate of these tumours, treated by transurethral resection, we investigated urothelial tumour, resection border and uninvolved urothelium. Urinary bladder samples were obtained from tumour free control subjects and patients with papilloma and papillary carcinoma. Immunohistochemical and immunoelectron labelling of uroplakins were performed. In normal human urothelium with continuous uroplakin-positive superficial cell layer uroplakins were localized to flattened mature fusiform vesicles and apical plasma membrane of umbrella cells. Diverse uroplakin expression was found in papilloma and papillary carcinoma. Three aberrant differentiation stages of urothelial cells, not found in normal urothelium, were recognized in tumours. Diverse uroplakin expression and aberrant differentiation were occasionally found in resection border and in uninvolved urothelium. We demonstrated here that uroplakin expression and localization in urothelial tumours is altered when compared to normal urothelium. In patients with papilloma and papillary carcinoma immunolabelling of uroplakins at ultrastructural level shows aberrant urothelial differentiation. It is possible that aberrant differentiation stages of urothelial cells in resection border and in uninvolved urothelium contribute to high recurrence rate

  3. Removal of urothelium affects bladder contractility and release of ATP but not release of NO in rat urinary bladder

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    Boone Timothy B

    2010-05-01

    Full Text Available Abstract Background The objective of our work was to investigate both the contractile function and the release of ATP and NO from strips of bladder tissue after removal of the urothelium. Methods The method of removal was a gentle swabbing motion rather than a sharp surgical cutting to separate the urothelium from the smooth muscle. The contractile response and ATP and NO release were measured in intact as well as on swabbed preparations. The removal of the urothelial layer was affirmed microscopically. Results After the swabbing, the smaller contractions were evoked by electrical as well as by chemical stimulation (50 μM carbachol or 50 μM α, β meATP. Electrical stimulation, carbachol and substance P (5 μM evoked lower release of ATP in the swabbed strips than in intact strips. Although release of NO evoked by electrical stimulation or substance P was not changed, release of NO evoked by carbachol was significantly less in the swabbed preparations. Conclusion Since swabbing removes only the urothelium, the presence of the suburothelial layer may explain the difference between our findings and those of others who found an increase in contractility. Evoked release of ATP is reduced in swabbed strips, indicating that ATP derives solely from the urothelium. On the other hand, electrical stimulation and substance P evoke identical degrees of NO release in both intact and swabbed preparations, suggesting that NO can be released from the suburothelium. Conversely, carbachol-induced release of NO is lower in swabbed strips, implying that the cholinergic receptors (muscarinic or nicotinic are located in the upper layer of the urothelium.

  4. Characterization of muscarinic and P2X receptors in the urothelium and detrusor muscle of the rat bladder

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    Masaki Ogoda

    2016-05-01

    Full Text Available Muscarinic and purinergic (P2X receptors play critical roles in bladder urothelium under physiological and pathological conditions. Aim of present study was to characterize these receptors in rat bladder urothelium and detrusor muscle using selective radioligands of [N-methyl-3H]scopolamine methyl chloride ([3H]NMS and αβ-methylene ATP [2,8-3H]tetrasodium salt ([3H]αβ-MeATP. Similar binding parameters for each radioligand were observed in urothelium and detrusor muscle. Pretreatment with N-(2-chloroethyl-4-piperidinyl diphenylacetate (4-DAMP mustard mustard revealed co-existence of M2 and M3 receptors, with the number of M2 receptors being larger in the urothelium and detrusor muscle. Intravesical administration of imidafenacin and Dpr-P-4 (N → O (active metabolite of propiverine displayed significant binding of muscarinic receptors in the urothelium and detrusor muscle. The treatment with cyclophosphamide (CYP or resiniferatoxin (RTX resulted in a significant decrease in maximal number of binding sites (Bmax for [3H]NMS and/or [3H]αβ-MeATP in the urothelium and detrusor muscle. These results demonstrated that 1 pharmacological characteristics of muscarinic and P2X receptors in rat bladder urothelium were similar to those in the detrusor muscle, 2 that densities of these receptors were significantly altered by pretreatments with CYP and RTX, and 3 that these receptors may be pharmacologically affected by imidafenacin and Dpr-P-4 (N → O which are excreted in the urine.

  5. PPARa and PPAR¿ coactivation rapidly induces Egr-1 in the nuclei of the dorsal and ventral urinary bladder and kidney pelvis urothelium of rats

    DEFF Research Database (Denmark)

    Egerod, Frederikke Lihme; Svendsen, Jette Eldrup; Hinley, Jennifer

    2009-01-01

    in the dorsal and ventral bladder urothelium, arguing against involvement of urinary solids. Egr-1 induction sometimes occurred in a localized fashion, indicating physiological microheterogeneity in the urothelium. The rapid kinetics supported that Egr-1 induction occurred as a result of pharmacological...... activation of PPAR alpha and PPAR gamma, which are coexpressed at high levels in the rat urothelium. Finally, our demonstration of a nuclear localization supports that the Egr-1 induced by PPAR alpha and PPAR gamma coactivation in the rat urothelium may be biologically active....

  6. In Vitro Differentiation and Propagation of Urothelium from Pluripotent Stem Cell Lines.

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    Osborn, Stephanie L; Kurzrock, Eric A

    2018-01-01

    Bioengineering of bladder tissue, particularly for those patients who have advanced bladder disease, requires a source of urothelium that is healthy, capable of significant proliferation in vitro and immunologically tolerated upon transplant. As pluripotent stem cells have the potential to fulfill such criteria, they provide a critical cell source from which urothelium might be derived in vitro and used clinically. Herein, we describe the in vitro differentiation of urothelium from the H9 human embryonic stem cell (hESC) line through the definitive endoderm (DE) phase via selective culture techniques. The protocol can be used to derive urothelium from other hESCs or human-induced pluripotent stem cells.

  7. Overexpression of Aquaporin-1 and Caveolin-1 in the Rat Urinary Bladder Urothelium Following Bladder Outlet Obstruction

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    Sun-Ouck Kim

    2013-12-01

    Full Text Available Purpose This study was designed to investigate the effect of detrusor overactivity induced by partial bladder outlet obstruction (BOO on the expression of aquaporin 1 (AQP1 and caveolin 1 (CAV1 in the rat urinary bladder, and to determine the role of these molecules in detrusor overactivity. Methods Female Sprague-Dawley rats were divided into control (n=30 and experimental (n=30 groups. The BOO group underwent partial BOO, and the control group underwent a sham operation. After 4 weeks, an urodynamic study was performed to measure the contraction interval and contraction pressure. The expression and cellular localization of AQP1 and CAV1 were determined by western blot and immunofluorescence experiments in the rat urinary bladder. Results In cystometrograms, the contraction interval was significantly lower in the BOO group (2.9±1.5 minutes than in the control group (6.7±1.0 minutes (P<0.05. Conversely, the average contraction pressure was significantly higher in the BOO group (21.2±3.3 mmHg than in the control group (13.0±2.5 mmHg (P<0.05. AQP1 and CAV1 were coexpressed in the capillaries, arterioles, and venules of the suburothelial layer. AQP1 and CAV1 protein expression was significantly increased in the BOO rats compared to the control rats (P<0.05. Conclusions Detrusor overactivity induced by BOO causes a significant increase in the expression of AQP1 and CAV1, which were coexpressed in the suburothelial microvasculature. This finding suggests that AQP1 and CAV1 might be closely related to bladder signal activity and may have a functional role in BOO-associated detrusor overactivity.

  8. Localization of P2X receptor subtypes 2, 3 and 7 in human urinary bladder.

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    Svennersten, Karl; Hallén-Grufman, Katarina; de Verdier, Petra J; Wiklund, N Peter; Poljakovic, Mirjana

    2015-08-08

    Voiding dysfunctions are a common problem that has a severe negative impact on the quality of life. Today there is a need for new drug targets for these conditions. The role of ATP receptors in bladder physiology has been studied for some time, primarily in animal models. The aim of this work is to investigate the localization of the ATP receptors P2X2, P2X3 and P2X7 and their colocalization with vimentin and actin in the human urinary bladder. Immunohistochemical analysis was conducted on full-thickness bladder tissues from fundus and trigonum collected from 15 patients undergoing open radical cystectomy due to chronic cystitis, bladder cancer or locally advanced prostate cancer. Colocalization analyses were performed between the three different P2X subtypes and the structural proteins vimentin and actin. Specimens were examined using epifluorescence microscopy and correlation coefficients were calculated for each costaining as well as the mean distance from the laminin positive basal side of the urothelium to the vimentin positive cells located in the suburothelium. P2X2 was expressed in vimentin positive cells located in the suburothelium. Less distinct labelling of P2X2 was also observed in actin positive smooth muscle cells and in the urothelium. P2X3 was expressed in vimentin positive cells surrounding the smooth muscle, and in vimentin positive cells located in the suburothelium. Weaker P2X3 labelling was seen in the urothelium. P2X7 was expressed in the smooth muscle cells and the urothelium. In the suburothelium, cells double positive for P2X2 and vimentin where located closer to the urothelium while cells double positive for P2X3 and vimentin where located further from the urothelium. The results from this study demonstrate that there is a significant difference in the expression of the purinergic P2X2, P2X3 and P2X7 receptors in the different histological layers of the human urinary bladder.

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

    International Nuclear Information System (INIS)

    Chung, Hong; Kim, Hong Sup; Kim, Bokyung; Jung, Seung-Hyo; Won, Kyung-Jong; Jiang, Xiaowen; Lee, Chang-Kwon; Lim, So Dug; Yang, Sang-Kuk; Song, Ki Hak

    2013-01-01

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

  10. Tumors of the upper urothelium

    International Nuclear Information System (INIS)

    Rafla, S.

    1975-01-01

    Forty-two cases of malignant tumors of renal pelvis were reviewed: 28 were transitional cell carcinomas; and 14 were squamous cell carcinomas. The natural history and spread of the disease is discussed in detail. Transitional cell carcinomas spread primarily to the ureter (40 percent), followed closely by the renal bed (33 percent) and bladder (30 percent). Squamous cell carcinomas spread primarily through the renal bed (60 percent), followed by the draining lymph nodes (28 percent). The spread to other regions (bones, splanchnic organs, chest, etc.), occurred with relatively less frequency, but more in squamous than transitional cell carcinomas. Transitional cell carcinomas seem to have a longer natural history than squamous cell carcinomas. Recurrences in bladder and the remainder of the urothelium seem to be controlled for relatively long periods of time, while those in lymph nodes and renal bed seem to be rapidly fatal. The results of treatment and factors influencing them are discussed. Patients suffering from transitional cell carcinomas faired better than those with squamous cell carcinomas at the 5 year mark (25 and 15 percent, respectively), but the 10 year results are poor in both. The role of radiotherapy in the treatment of these tumors and the influencing factors are also discussed in detail. The response of these tumors to radiotherapy seems to be akin to that of the lower urothelium (bladder), provided adequate dosage is delivered to the relevant volume at the proper moment in time. (U.S.)

  11. Understanding the development of human bladder cancer by using a whole-organ genomic mapping strategy.

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    Majewski, Tadeusz; Lee, Sangkyou; Jeong, Joon; Yoon, Dong-Sup; Kram, Andrzej; Kim, Mi-Sook; Tuziak, Tomasz; Bondaruk, Jolanta; Lee, Sooyong; Park, Weon-Seo; Tang, Kuang S; Chung, Woonbok; Shen, Lanlan; Ahmed, Saira S; Johnston, Dennis A; Grossman, H Barton; Dinney, Colin P; Zhou, Jain-Hua; Harris, R Alan; Snyder, Carrie; Filipek, Slawomir; Narod, Steven A; Watson, Patrice; Lynch, Henry T; Gazdar, Adi; Bar-Eli, Menashe; Wu, Xifeng F; McConkey, David J; Baggerly, Keith; Issa, Jean-Pierre; Benedict, William F; Scherer, Steven E; Czerniak, Bogdan

    2008-07-01

    The search for the genomic sequences involved in human cancers can be greatly facilitated by maps of genomic imbalances identifying the involved chromosomal regions, particularly those that participate in the development of occult preneoplastic conditions that progress to clinically aggressive invasive cancer. The integration of such regions with human genome sequence variation may provide valuable clues about their overall structure and gene content. By extension, such knowledge may help us understand the underlying genetic components involved in the initiation and progression of these cancers. We describe the development of a genome-wide map of human bladder cancer that tracks its progression from in situ precursor conditions to invasive disease. Testing for allelic losses using a genome-wide panel of 787 microsatellite markers was performed on multiple DNA samples, extracted from the entire mucosal surface of the bladder and corresponding to normal urothelium, in situ preneoplastic lesions, and invasive carcinoma. Using this approach, we matched the clonal allelic losses in distinct chromosomal regions to specific phases of bladder neoplasia and produced a detailed genetic map of bladder cancer development. These analyses revealed three major waves of genetic changes associated with growth advantages of successive clones and reflecting a stepwise conversion of normal urothelial cells into cancer cells. The genetic changes map to six regions at 3q22-q24, 5q22-q31, 9q21-q22, 10q26, 13q14, and 17p13, which may represent critical hits driving the development of bladder cancer. Finally, we performed high-resolution mapping using single nucleotide polymorphism markers within one region on chromosome 13q14, containing the model tumor suppressor gene RB1, and defined a minimal deleted region associated with clonal expansion of in situ neoplasia. These analyses provided new insights on the involvement of several non-coding sequences mapping to the region and identified

  12. Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer.

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    Kauffman, Eric C; Robinson, Brian D; Downes, Martin J; Powell, Leagh G; Lee, Ming Ming; Scherr, Douglas S; Gudas, Lorraine J; Mongan, Nigel P

    2011-12-01

    Bladder cancer is approximately three times more common in men as compared to women. We and others have previously investigated the contribution of androgens and the androgen receptor (AR) to bladder cancer. JMJD2A and LSD1 are recently discovered AR coregulator proteins that mediate AR-dependent transcription via recently described histone lysine-demethylation (KDM) mechanisms. We used immunohistochemistry to examine JMJD2A, LSD1, and AR expression in 72 radical cystectomy specimens, resulting in evaluation of 129 tissue samples (59 urothelial carcinoma, 70 benign). We tested levels of these proteins for statistical association with clinicopathologic variables and patient survival. Expression of these markers was also assessed in human bladder cancer cell lines. The effects of pharmacological inhibition of LSD1 on the proliferation of these bladder cancer cells was determined. JMJD2A and AR levels were significantly lower in malignant versus benign urothelium, while increased LSD1 levels were observed in malignant urothelium relative to benign. A significant reduction in all three proteins occurred with cancer stage progression, including muscle invasion (JMJD2A/LSD1/AR), extravesical extension (JMJD2A/LSD1), and lymph node metastasis (JMJD2A/AR). Lower JMJD2A intensity correlated with additional poor prognostic features, including lymphovascular invasion, concomitant carcinoma in situ and tobacco usage, and predicted significantly worse overall survival. Pharmacological inhibition of LSD1 suppressed bladder cancer cell proliferation and androgen-induced transcription. Our results support a novel role for the AR-KDM complex in bladder cancer initiation and progression, identify JMJD2A as a promising prognostic biomarker, and demonstrate targeting of the KDM activity as an effective potential approach for bladder cancer growth inhibition. Copyright © 2011 Wiley Periodicals, Inc.

  13. 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...

  14. SOX4 expression in bladder carcinoma

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    Aaboe, Mads; Birkenkamp-Demtroder, Karin; Wiuf, Carsten

    2006-01-01

    The human transcription factor SOX4 was 5-fold up-regulated in bladder tumors compared with normal tissue based on whole-genome expression profiling of 166 clinical bladder tumor samples and 27 normal urothelium samples. Using a SOX4-specific antibody, we found that the cancer cells expressed...... in the clinical bladder material and a small subset of the genes showed a high correlation to SOX4 expression. The present data suggest a role of SOX4 in the bladder cancer disease....... the SOX4 protein and, thus, did an evaluation of SOX4 protein expression in 2,360 bladder tumors using a tissue microarray with clinical annotation. We found a correlation (P bladder cell line HU609, SOX4...

  15. Human bladder cancer diagnosis using multiphoton microscopy

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    Mukherjee, Sushmita; Wysock, James S.; Ng, Casey K.; Akhtar, Mohammed; Perner, Sven; Lee, Ming-Ming; Rubin, Mark A.; Maxfield, Frederick R.; Webb, Watt W.; Scherr, Douglas S.

    2009-02-01

    At the time of diagnosis, approximately 75% of bladder cancers are non-muscle invasive. Appropriate diagnosis and surgical resection at this stage improves prognosis dramatically. However, these lesions, being small and/or flat, are often missed by conventional white-light cystoscopes. Furthermore, it is difficult to assess the surgical margin for negativity using conventional cystoscopes. Resultantly, the recurrence rates in patients with early bladder cancer are very high. This is currently addressed by repeat cystoscopies and biopsies, which can last throughout the life of a patient, increasing cost and patient morbidity. Multiphoton endoscopes offer a potential solution, allowing real time, noninvasive biopsies of the human bladder, as well as an up-close assessment of the resection margin. While miniaturization of the Multiphoton microscope into an endoscopic format is currently in progress, we present results here indicating that Multiphoton imaging (using a bench-top Multiphoton microscope) can indeed identify cancers in fresh, unfixed human bladder biopsies. Multiphoton images are acquired in two channels: (1) broadband autofluorescence from cells, and (2) second harmonic generation (SHG), mostly by tissue collagen. These images are then compared with gold standard hematoxylin/eosin (H&E) stained histopathology slides from the same specimen. Based on a "training set" and a very small "blinded set" of samples, we have found excellent correlation between the Multiphoton and histopathological diagnoses. A larger blinded analysis by two independent uropathologists is currently in progress. We expect that the conclusion of this phase will provide us with diagnostic accuracy estimates, as well as the degree of inter-observer heterogeneity.

  16. Immunoelectron microscopic localisation of keratin and luminal epithelial antigens in normal and neoplastic urothelium.

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    Wilson, P D; Nathrath, W B; Trejdosiewicz, L K

    1982-01-01

    Immunoelectron microscope cytochemistry was carried out on 2% paraformaldehyde fixed, 50 mu sections of normal urothelium and bladder carcinoma cells in culture using antisera raised in rabbits to human 40-63 000 MW epidermal "broad spectrum" keratin and calf urothelial "luminal epithelial antigen" (aLEA) Both the unconjugated and indirect immunoperoxidase-DAB techniques were used before routine embedding. The localisation of both keratin and luminal epithelial antigen (LEA) was similar in normal and neoplastic cells and reaction product was associated not only with tonofilaments but also lining membrane vesicles and on fine filaments in the cytoplasmic ground substance.

  17. Differentiation of human endometrial stem cells into urothelial cells on a three-dimensional nanofibrous silk-collagen scaffold: an autologous cell resource for reconstruction of the urinary bladder wall.

    Science.gov (United States)

    Shoae-Hassani, Alireza; Mortazavi-Tabatabaei, Seyed Abdolreza; Sharif, Shiva; Seifalian, Alexander Marcus; Azimi, Alireza; Samadikuchaksaraei, Ali; Verdi, Javad

    2015-11-01

    Reconstruction of the bladder wall via in vitro differentiated stem cells on an appropriate scaffold could be used in such conditions as cancer and neurogenic urinary bladder. This study aimed to examine the potential of human endometrial stem cells (EnSCs) to form urinary bladder epithelial cells (urothelium) on nanofibrous silk-collagen scaffolds, for construction of the urinary bladder wall. After passage 4, EnSCs were induced by keratinocyte growth factor (KGF) and epidermal growth factor (EGF) and seeded on electrospun collagen-V, silk and silk-collagen nanofibres. Later we tested urothelium-specific genes and proteins (uroplakin-Ia, uroplakin-Ib, uroplakin-II, uroplakin-III and cytokeratin 20) by immunocytochemistry, RT-PCR and western blot analyses. Scanning electron microscopy (SEM) and histology were used to detect cell-matrix interactions. DMEM/F12 supplemented by KGF and EGF induced EnSCs to express urothelial cell-specific genes and proteins. Either collagen, silk or silk-collagen scaffolds promoted cell proliferation. The nanofibrous silk-collagen scaffolds provided a three-dimensional (3D) structure to maximize cell-matrix penetration and increase differentiation of the EnSCs. Human EnSCs seeded on 3D nanofibrous silk-collagen scaffolds and differentiated to urothelial cells provide a suitable source for potential use in bladder wall reconstruction in women. Copyright © 2013 John Wiley & Sons, Ltd.

  18. β-adrenoceptor agonist effects in experimental models of bladder dysfunction

    NARCIS (Netherlands)

    Michel, Martin C.; Ochodnicky, Peter; Homma, Yukio; Igawa, Yasuhiko

    2011-01-01

    β-adrenoceptor stimulation can enhance the storage function of the urinary bladder by acting on detrusor smooth muscle tone, mediator release from the urothelium and/or afferent nerve activity. In humans this may occur predominantly if not exclusively via the β₃-subtype. The effects of

  19. Induction of genetic instability in ρ53 in primary cultures of normal human urothelium exposed low-dose of gamma radiation

    International Nuclear Information System (INIS)

    Colucci, S.; Mothersill, C.; Seymour, C.; Harney, J.; Gamble, S.; Arrand, J.

    1997-01-01

    We have previously shown that primary explant cultures of human urothelium exposed to low doses of gamma radiation subsequently exhibit a high level of stable P53 but it was not clear from those studies whether this protein stabilisation occurred through epigenetic events or as a result of mutation. In these experiments, primary urothelium cultures from five different patients were exposed to 0.5 and 5 Gy γ- radiation from a 60 Cobalt source and allowed to grow for 7- 10 division cycles to allow development of any radiation-induced, non lethal changes in the urothelial cells. C-myc, Bcl-2, and stable P53 protein expression was found to be elevated in cultures following both radiation doses. Following 0.5 Gy exposure, the cultures also developed multiple distinct 'foci' of rapidly-dividing cells which strongly over-expressed P53. These grew on a background of morphologically normal cells. When such foci were selectively analysed for their p53 mutation status by PCR-SSCPE, there was evidence that they contained cells which had developed changes to thr p53 gene post-irradiation. These changes appeared to occur more frequently in focal cells than in cells of normal morphological appearance in the same culture. DNA sequence analysis of the p53 gene in 0.5 Gy-induced foci displayed frame shift mutations in some cases. These results may have mechanistic importance given the controversy regarding low-dose radiation effects and p53-related genomic instability. (authors)

  20. Downregulation of Checkpoint Protein Kinase 2 in the Urothelium of Healthy Male Tobacco Smokers.

    Science.gov (United States)

    Breyer, Johannes; Denzinger, Stefan; Hartmann, Arndt; Otto, Wolfgang

    2016-01-01

    With this letter to the editor we present for the first time a study on CHEK2 expression in normal urothelium of healthy male smokers, former smokers and non-smokers. We could show a statistically significant downregulation of this DNA repair gene in current smokers compared to non-smokers, suggesting that smoking downregulates CHEK2 in normal urothelium, probably associated with an early step in carcinogenesis of urothelial bladder carcinoma. © 2016 S. Karger AG, Basel.

  1. Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations

    Directory of Open Access Journals (Sweden)

    Benham Christopher D

    2006-03-01

    Full Text Available Abstract Background The recent identification of the cold-menthol sensory receptor (TRPM8; CMR1, provides us with an opportunity to advance our understanding of its role in the pathophysiology of bladder dysfunction, and its potential mediation of the bladder cooling reflex. In this study, we report the distribution of the cool and menthol receptor TRPM8 in the urinary bladder in patients with overactive and painful bladder syndromes, and its relationship with clinical symptoms. Methods Bladder specimens obtained from patients with painful bladder syndrome (PBS, n = 16, idiopathic detrusor overactivity (IDO, n = 14, and asymptomatic microscopic hematuria (controls, n = 17, were immunostained using specific antibodies to TRPM8; nerve fibre and urothelial immunostaining were analysed using fibre counts and computerized image analysis respectively. The results of immunohistochemistry were compared between the groups and correlated with the Pain, Frequency and Urgency scores. Results TRPM8-immunoreactive staining was observed in the urothelium and nerve fibres scattered in the suburothelium. The nerve fibre staining was seen in fine-calibre axons and thick (myelinated fibres. There was marked increase of TRPM8-immunoreactive nerve fibres in IDO (P = 0.0249 and PBS (P Conclusion This study demonstrates increased TRPM8 in nerve fibres of overactive and painful bladders, and its relationship with clinical symptoms. TRPM8 may play a role in the symptomatology and pathophysiology of these disorders, and may provide an additional target for future overactive and painful bladder pharmacotherapy.

  2. Loss of prostasin (PRSS8) in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT)

    International Nuclear Information System (INIS)

    Chen, Li-Mei; Verity, Nicole J; Chai, Karl X

    2009-01-01

    The glycosylphosphatidylinositol (GPI)-anchored epithelial extracellular membrane serine protease prostasin (PRSS8) is expressed abundantly in normal epithelia and essential for terminal epithelial differentiation, but down-regulated in human prostate, breast, and gastric cancers and invasive cancer cell lines. Prostasin is involved in the extracellular proteolytic modulation of the epidermal growth factor receptor (EGFR) and is an invasion suppressor. The aim of this study was to evaluate prostasin expression states in the transitional cell carcinomas (TCC) of the human bladder and in human TCC cell lines. Normal human bladder tissues and TCC on a bladder cancer tissue microarray (TMA) were evaluated for prostasin expression by means of immunohistochemistry. A panel of 16 urothelial and TCC cell lines were evaluated for prostasin and E-cadherin expression by western blot and quantitative PCR, and for prostasin gene promoter region CpG methylation by methylation-specific PCR (MSP). Prostasin is expressed in the normal human urothelium and in a normal human urothelial cell line, but is significantly down-regulated in high-grade TCC and lost in 9 (of 15) TCC cell lines. Loss of prostasin expression in the TCC cell lines correlated with loss of or reduced E-cadherin expression, loss of epithelial morphology, and promoter DNA hypermethylation. Prostasin expression could be reactivated by demethylation or inhibition of histone deacetylase. Re-expression of prostasin or a serine protease-inactive variant resulted in transcriptional up-regulation of E-cadherin. Loss of prostasin expression in bladder transitional cell carcinomas is associated with epithelial-mesenchymal transition (EMT), and may have functional implications in tumor invasion and resistance to chemotherapy

  3. Loss of prostasin (PRSS8 in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT

    Directory of Open Access Journals (Sweden)

    Chai Karl X

    2009-10-01

    Full Text Available Abstract Background The glycosylphosphatidylinositol (GPI-anchored epithelial extracellular membrane serine protease prostasin (PRSS8 is expressed abundantly in normal epithelia and essential for terminal epithelial differentiation, but down-regulated in human prostate, breast, and gastric cancers and invasive cancer cell lines. Prostasin is involved in the extracellular proteolytic modulation of the epidermal growth factor receptor (EGFR and is an invasion suppressor. The aim of this study was to evaluate prostasin expression states in the transitional cell carcinomas (TCC of the human bladder and in human TCC cell lines. Methods Normal human bladder tissues and TCC on a bladder cancer tissue microarray (TMA were evaluated for prostasin expression by means of immunohistochemistry. A panel of 16 urothelial and TCC cell lines were evaluated for prostasin and E-cadherin expression by western blot and quantitative PCR, and for prostasin gene promoter region CpG methylation by methylation-specific PCR (MSP. Results Prostasin is expressed in the normal human urothelium and in a normal human urothelial cell line, but is significantly down-regulated in high-grade TCC and lost in 9 (of 15 TCC cell lines. Loss of prostasin expression in the TCC cell lines correlated with loss of or reduced E-cadherin expression, loss of epithelial morphology, and promoter DNA hypermethylation. Prostasin expression could be reactivated by demethylation or inhibition of histone deacetylase. Re-expression of prostasin or a serine protease-inactive variant resulted in transcriptional up-regulation of E-cadherin. Conclusion Loss of prostasin expression in bladder transitional cell carcinomas is associated with epithelial-mesenchymal transition (EMT, and may have functional implications in tumor invasion and resistance to chemotherapy.

  4. Concepts in causality: chemically induced human urinary bladder cancer

    International Nuclear Information System (INIS)

    Lower, G.M. Jr.

    1982-01-01

    A significant portion of the incidence of human urinary bladder cancer can be attributed to occupational and cultural (tobacco smoking) situations associated with exposures to various arylamines, many of which represent established human carcinogens. A brief historical overview of research in bladder cancer causality indicates that the identification of causal agents and causal mechanism has been approached and rests upon information gathered at the organismal (geographical/historical), cellular, and molecular levels of biologic organization. This viewpoint speaks of a natural evolution within the biomedical sciences; a natural evolution from descriptive approaches to mechanistic approaches; and a natural evolution from more or less independent discipline-oriented approaches to hierarchically organized multidisciplinary approaches. Available information relevant to bladder cancer causality can be readily integrated into general conceptual frameworks to yield a hierarchial view of the natural history of urinary bladder cancer, a view consistent with contemporary natural systems and information theory and perhaps relevant also to other chemically induced epithelial cancers. Such frameworks are useful in appreciating the spatial and temporal boundaries and interrelationships in causality and the conceptual interrelationships within the biomedical sciences. Recent approaches in molecular epidemiology and the assessment of relative individual susceptibility to bladder cancer indicate that such frameworks are useful in forming hypotheses

  5. Artificial sweeteners and human bladder cancer.

    Science.gov (United States)

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

    1977-09-17

    A positive association between the use of artificial sweetners, particularly saccharin, and risk of bladder cancer in males has been observed in a case-control study of 480 men and 152 women in three Provinces in Canada. The risk ratio for ever versus never used is 1-6 for males (P=0-009, one-tailed test), and a significant dose-response relationship was obtained for both duration and frequency of use. The population attributable risk for males is estimated at 7%, though for diabetics, who have a similar risk ratio for artificial sweetner use as non-diabetics, the attributable risk is 33%.

  6. Membrane microdomain-associated uroplakin IIIa contributes to Src-dependent mechanisms of anti-apoptotic proliferation in human bladder carcinoma cells

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    Shigeru Kihira

    2012-08-01

    Our previous study demonstrated that tyrosine phosphorylation of p145met/β-subunit of hepatocyte growth factor receptor by epidermal growth factor receptor and Src contributes to the anti-apoptotic growth of human bladder carcinoma cell 5637 under serum-starved conditions. Here, we show that some other cell lines of human bladder carcinoma, but not other types of human cancer cells, also exhibit Src-dependent, anti-apoptotic proliferation under serum-starved conditions, and that low-density, detergent-insoluble membrane microdomains (MD serve as a structural platform for signaling events involving p145met, EGFR, and Src. As an MD-associated molecule that may contribute to bladder carcinoma-specific cellular function, we identified uroplakin IIIa (UPIIIa, an urothelium-specific protein. Results obtained so far revealed: 1 UPIIIa undergoes partial proteolysis in serum-starved cells; 2 a specific antibody to the extracellular domain of UPIIIa inhibits the proteolysis of UPIIIa and the activation of Src, and promotes apoptosis in serum-starved cells; and 3 knockdown of UPIIIa by short interfering RNA also promotes apoptosis in serum-starved cells. GM6001, a potent inhibitor of matrix metalloproteinase (MMP, inhibits the proteolysis of UPIIIa and promotes apoptosis in serum-starved cells. Furthermore, serum starvation promotes expression and secretion of the heparin-binding EGF-like growth factor in a manner that depends on the functions of MMP, Src, and UPIIIa. These results highlight a hitherto unknown signaling network involving a subset of MD-associated molecules in the anti-apoptotic mechanisms of human bladder carcinoma cells.

  7. AB286. SPR-13 Sex differences and participation of Toll-like receptor 4 to rat bladder contractile function

    Science.gov (United States)

    Szasz, Theodora; Burgess, Beth; Webb, R. Clinton

    2016-01-01

    Objective Innate immune mechanisms have been implicated in the pathophysiology of chronic sterile conditions such as hypertension and diabetes. We have recently demonstrated that Toll-like receptor 4 (TLR4) activation by endogenous molecules such as high mobility group box-1 (HMGB1) contributes to hypertrophy and hypercontractility in diabetic bladder dysfunction. It has been reported that women have a higher frequency of overactive bladder symptoms, while men have higher detrusor overactivity. We hypothesized that sex differences in the contribution of TLR4 to bladder contraction may underlie the sex differences observed clinically. Methods Female and male rat bladder contractile responses to carbacholine (CCh) and electrical field stimulation (EFS) were measured in the presence and absence of TLR4 inhibitor CLI-095 and in the presence and absence of urothelium. Results We observed that contractile responses to both CCh and EFS were higher in the male than the female bladder segments in both the presence and absence of urothelium [CCh Emax (mN): male + urothelium =84.3±1.2, male – urothelium =83.7±1.2, female + urothelium =49.8±0.8, female – urothelium =59.2±1.1; EFS 32 Hz (mN): male + urothelium= 84.9±7.1, male – urothelium =66.8±5.2, female + urothelium =57.8±5.9, female – urothelium =54.5±3.5]. Incubation of bladder segments with the TLR4 inhibitor CLI-095 significantly decreased contractile responses to both CCh and EFS in both sexes, irrespective of the presence of urothelium [CCh Emax (mN): male + urothelium =91.1±0.8, male – urothelium =75.4±1.8, female + urothelium =42.9±1.1, female – urothelium =52.5±1.1; EFS 32 Hz (mN): male + urothelium =80.8±7.9, male – urothelium =59.6±10.6, female + urothelium =43.3±2.6, female – urothelium =46.4±1.9]. Conclusions Our data suggest that although there are sex differences in the contractile function of the rat bladder in basal conditions, the participation of TLR4 to bladder contraction

  8. Bladder uptake of liposomes after intravesical administration occurs by endocytosis.

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    Bharathi Raja Rajaganapathy

    Full Text Available Liposomes have been used therapeutically and as a local drug delivery system in the bladder. However, the exact mechanism for the uptake of liposomes by bladder cells is unclear. In the present study, we investigated the role of endocytosis in the uptake of liposomes by cultured human UROtsa cells of urothelium and rat bladder. UROtsa cells were incubated in serum-free media with liposomes containing colloidal gold particles for 2 h either at 37°C or at 4°C. Transmission Electron Microscopy (TEM images of cells incubated at 37°C found endocytic vesicles containing gold inside the cells. In contrast, only extracellular binding was noticed in cells incubated with liposomes at 4°C. Absence of liposome internalization at 4°C indicates the need of energy dependent endocytosis as the primary mechanism of entry of liposomes into the urothelium. Flow cytometry analysis revealed that the uptake of liposomes at 37°C occurs via clathrin mediated endocytosis. Based on these observations, we propose that clathrin mediated endocytosis is the main route of entry for liposomes into the urothelial layer of the bladder and the findings here support the usefulness of liposomes in intravesical drug delivery.

  9. Conditional Expression of the Androgen Receptor Increases Susceptibility of Bladder Cancer in Mice.

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    Daniel T Johnson

    Full Text Available Bladder cancer represents a significant human tumor burden, accounting for about 7.7% and 2.4% of all cancer cases in males and females, respectively. While men have a higher risk of developing bladder cancer, women tend to present at a later stage of disease and with more aggressive tumors. Previous studies have suggested a promotional role of androgen signaling in enhancing bladder cancer development. To directly assess the role of androgens in bladder tumorigenesis, we have developed a novel transgenic mouse strain, R26hARLoxP/+:Upk3aGCE/+, in which the human AR transgene is conditionally expressed in bladder urothelium. Intriguingly, both male and female R26hARLoxP/+:Upk3aGCE/+ mice display a higher incidence of urothelial cell carcinoma (UCC than the age and sex matched control littermates in response to the carcinogen, N-butyl-N-(4-hydroxybutyl nitrosamine (BBN. We detect expression of the human AR transgene in CK5-positive and p63-positive basal cells in bladder urothelium. Further analyses of UCC tissues from R26hARLoxP/+:Upk3aGCE/+ mice showed that the majority of tumor cells are of urothelial basal cell origin. Positive immunostaining of transgenic AR protein was observed in the majority of tumor cells of the transgenic mice, providing a link between transgenic AR expression and oncogenic transformation. We observed an increase in Ki67 positive cells within the UCC lesions of transgenic AR mice. Manipulating endogenous androgen levels by castration and androgen supplementation directly affected bladder tumor development in male and female R26hARLoxP/+:Upk3aGCE/+ mice, respectively. Taken together, our data demonstrate for the first time that conditional activation of transgenic AR expression in bladder urothelium enhances carciongen-induced bladder tumor formation in mice. This new AR transgenic mouse line mimics certain features of human bladder cancer and can be used to study bladder tumorigenesis and for drug development.

  10. 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. ©2016 American

  11. [High oncogenic risk human papillomavirus and urinary bladder cancer].

    Science.gov (United States)

    Loran, O B; Sinyakova, L A; Gundorova, L V; Kosov, V A; Kosova, I V; Pogodina, I E; Kolbasov, D N

    2017-07-01

    To determine the role of human papillomavirus (HPV) of high oncogenic risk in the development of urinary bladder cancer. 100 patients (72 men and 28 women) aged 38 to 90 years (mean age 65+/-10 years) diagnosed with bladder cancer were examined and underwent treatment. Clinical assessment was complemented by enzyme-linked immunosorbent assays for the presence of antiviral antibodies to herpes simplex virus (HSV) type 1 and type 2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), urethra scraping for detecting high oncogenic risk HPV. Tumor tissue was sampled for PCR virus detection. Semi-quantitative analysis was used to evaluate the components of lymphocyte-plasmocyte and leukocyte infiltrates and cytopathic changes in tumor tissue. There were positive correlations between cytopathic cell changes (koylocytosis and intranuclear inclusions, as manifestations of HPV) and the level of antiviral antibodies, the presence of viruses in the tumor, as well as with the components of the lymphoid-plasmocyte infiltrate. Negative correlations were found between the presence of papillomatosis and the above changes. Human papillomavirus is believed to be a trigger for the initiation of a tumor in young patients with a latent infection (CMV and EBV, HSV, HPV). Cytopathic changes (kylocytosis and intranuclear inclusions) were associated with the activity and morphological features of herpes-viral infections. Their degree varied depending on the stage of the process, but not on the anaplasia degree. Papillomatosis is associated with a more favorable course of the tumor process.

  12. Applications of Nanotechnology in Bladder Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jong-Wei Hsu

    2012-01-01

    Full Text Available Effective therapies can prevent superficial bladder cancer from developing into muscle-invasive stage or more severe stages which require radical cystectomy and negatively affect life quality. In terms of therapeutic approaches against superficial bladder cancer, intravesical (regional therapy has several advantages over oral (systemic therapy. Though urologists can directly deliver drugs to bladder lesions by intravesical instillation after transurethral resection, the efficacy of conventional drug delivery is usually low due to the bladder permeability barrier and bladder periodical discharge. Nanoparticles have been well developed as pharmaceutical carriers. By their versatile properties, nanoparticles can greatly improve the interactions between urothelium and drugs and also enhance the penetration of drugs into urothelium with lesions, which dramatically improves therapeutic efficacy. In this review, we discuss the advances of nanotechnology in bladder cancer therapy by different types of nanoparticles with different encapsulating materials.

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

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    Sheng-Chun Chiu

    2014-09-01

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

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

    Science.gov (United States)

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

    2016-05-10

    Bladder cancer is observed worldwide having been associated with a host of environmental and lifestyle risk factors. Recent investigations on anti-inflammatory glucocorticoid signaling point to a pathway that may impact bladder cancer. Here we show an inverse effect on the glucocorticoid receptor (GR) isoform signaling that may lead to bladder cancer. We found similar GRα expression levels in the transitional uroepithelial cancer cell lines T24 and UMUC-3. However, the T24 cells showed a significant (p bladder cancer cells. Therefore, GRβ may have a significant role in bladder cancer, and possibly serve as a therapeutic target for the disease.

  15. PIXE analysis of cancer-afflicted human bladder

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-07-01

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

  16. Estrogen receptors in the human male bladder, prostatic urethra, and prostate. An immunohistochemical and biochemical study

    DEFF Research Database (Denmark)

    Bødker, A; Balslev, E; Juul, B R

    1995-01-01

    The distribution and quantity of estrogen receptors (ERs) in the human male bladder, prostatic urethra and the prostate were studied in eight males with recurrent papillomas of the bladder or monosymptomatic hematuria (median age 61 years), 14 men undergoing transurethral resection due to benign...

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

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    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.

  18. Comparative study of the organisation and phenotypes of bladder interstitial cells in human, mouse and rat.

    Science.gov (United States)

    Gevaert, Thomas; Neuhaus, Jochen; Vanstreels, Els; Daelemans, Dirk; Everaerts, Wouter; Der Aa, Frank Van; Timmermans, Jean-Pierre; Roskams, Tania; Steiner, Clara; Pintelon, Isabel; De Ridder, Dirk

    2017-12-01

    With most research on interstitial cells (IC) in the bladder being conducted on animal models, it remains unclear whether all structural and functional data on IC from animal models can be translated to the human context. This prompted us to compare the structural and immunohistochemical properties of IC in bladders from mouse, rat and human. Tissue samples were obtained from the bladder dome and subsequently processed for immunohistochemistry and electron microscopy. The ultrastructural properties of IC were compared by means of electron microscopy and IC were additionally characterized with single/double immunohistochemistry/immunofluorescence. Our results reveal a similar organization of the IC network in the upper lamina propria (ULP), the deep lamina propria (DLP) and the detrusor muscle in human, rat and mouse bladders. Furthermore, despite several similarities in IC phenotypes, we also found several obvious inter-species differences in IC, especially in the ULP. Most remarkably in this respect, ULP IC in human bladder predominantly displayed a myoid phenotype with abundant presence of contractile micro-filaments, while those in rat and mouse bladders showed a fibroblast phenotype. In conclusion, the organization of ULP IC, DLP IC and detrusor IC is comparable in human, rat and mouse bladders, although several obvious inter-species differences in IC phenotypes were found. The present data show that translating research data on IC in laboratory animals to the human setting should be carried out with caution.

  19. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Albrechtsen, Reidar; Dyrskjøt, Lars; Rudkjaer, Lise

    2006-01-01

    PURPOSE: We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. EXPERIMENTAL DESIGN: ADAM12...... gene expression was evaluated in tumors from 96 patients with bladder cancer using a customized Affymetrix GeneChip. Gene expression in bladder cancer was validated using reverse transcription-PCR, quantitative PCR, and in situ hybridization. Protein expression was evaluated by immunohistochemical...... staining on tissue arrays of bladder cancers. The presence and relative amount of ADAM12 in the urine of cancer patients were determined by Western blotting and densitometric measurements, respectively. RESULTS: ADAM12 mRNA expression was significantly up-regulated in bladder cancer, as determined...

  20. Adherence of urease-induced crystals to rat bladder epithelium.

    Science.gov (United States)

    Grenabo, L; Hedelin, H; Pettersson, S

    1988-01-01

    Apart from urine supersaturation with respect to struvite and calcium phosphate caused by urease-producing microorganisms, retention of formed crystals in the urinary tract is necessary for the formation of infection stones. This study was performed to investigate the role of the mucous coat lining the urothelium in the adhesion of urease-induced crystals. Removal of this glycosaminoglycan-containing layer from rat bladders increased the adherence of struvite and calcium phosphate crystals 5-6 times compared to that in intact rat bladders. Heparin completely restored the antiadherence capacity while chondroitin sulphate had a very weak restorative effect and human urine had no restorative effect. These findings support the view that the mucous coat is of importance in preventing retention of urease-induced crystals.

  1. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Albrechtsen, Reidar; Dyrskjøt, Lars; Rudkjaer, Lise

    2006-01-01

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

  2. Lewis antigen mediated adhesion of freshly removed human bladder tumors to E-selectin

    DEFF Research Database (Denmark)

    Skorsteensgaard, Karna; Vestergaard, Else Marie; Langkilde, Niels

    1999-01-01

    PURPOSE: Twenty fresh surgical specimens of human bladder tumors were tested for their ability to adhere to recombinant P and E-selectin. The adhesion was correlated to immunological detection of carbohydrate structures. MATERIALS AND METHODS: A static titertray assay with immobilized selectins.......003), whereas no correlation was found to secretor and Lewis genotypes. CONCLUSIONS: These data on clinical specimens indicate that Lewis antigen mediated E-selectin adhesion may play a role in the human bladder cancer disease....

  3. Do neural tube defects lead to structural alterations in the human bladder?

    Science.gov (United States)

    Pazos, Helena M F; Lobo, Márcio Luiz de P; Costa, Waldemar S; Sampaio, Francisco J B; Cardoso, Luis Eduardo M; Favorito, Luciano Alves

    2011-05-01

    Anencephaly is the most severe neural tube defect in human fetuses. The objective of this paper is to analyze the structure of the bladder in anencephalic human fetuses. We studied 40 bladders of normal human fetuses (20 male and 20 female, aged 14 to 23 WPC) and 12 bladders of anencephalic fetuses (5 male and 7 female, aged 18 to 22 WPC). The bladders were removed and processed by routine histological techniques. Stereological analysis of collagen, elastic system fibers and smooth muscle was performed in sections. Data were expressed as volumetric density (Vv-%). The images were captured with Olympus BX51 microscopy and Olympus DP70 camera. The stereological analysis was done using the software Image Pro and Image J. For biochemical analysis, samples were fixed in acetone, and collagen concentrations were expressed as micrograms of hydroxyproline per mg of dry tissue. Means were statistically compared using the unpaired t-test (p<0.05). We observed a significant increase (p<0.0001) in the Vv of collagen in the bladders of anencephalic fetuses (69.71%) when compared to normal fetuses (52.74%), and a significant decrease (p<0.0001) in the Vv of smooth muscle cells in the bladders of anencephalic fetuses (23.96%) when compared to normal fetuses (38.35%). The biochemical analyses showed a higher concentration of total collagen in the bladders of anencephalic fetuses (37354 µg/mg) when compared to normal fetuses (48117 µg/mg, p<0.02). The structural alterations of the bladder found in this study may suggest the existence of functional alterations in the bladder of anencephalic human fetuses.

  4. Study of Arachidonic Acid Pathway in Human Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama

    2009-12-01

    Full Text Available Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and tumorigenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.

  5. Study of Arachidonic Acid Pathway in Human Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama

    2009-01-01

    Full Text Available Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and tumorigenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-28

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

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

    International Nuclear Information System (INIS)

    Zheng, Jiajia; Zhu, Xi; Zhang, Jie

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Background Human TOX3 (TOX high mobility group box family member 3) regulates Ca2+-dependent transcription in neurons and has been associated with breast cancer susceptibility. Aim of the study was to investigate the expression of TOX3 in bladder cancer tissue samples and to identify genes...... urothelium. Microarray expression profiling of human bladder cancer cells overexpressing TOX3 followed by Pathway analysis showed that TOX3 overexpression mainly affected the Interferon Signaling Pathway. TOX3 upregulation induced the expression of several genes with a gamma interferon activation site (GAS......), e.g. STAT1. In vitro functional studies showed that TOX3 was able to bind to the GAS-sequence located at the STAT1 promoter. siRNA mediated knockdown of TOX3 in RT4 bladder cancer cells decreased STAT1 expression suggesting a direct impact of TOX3 on STAT1. Immunoprecipitation of TOX3 overexpressing...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Background: Human TOX3 (TOX high mobility group box family member 3) regulates Ca2+ dependent transcription in neurons and has been associated with breast cancer susceptibility. Aim of the study was to investigate the expression of TOX3 in bladder cancer tissue samples and to identify genes...... urothelium. Microarray expression profiling of human bladder cancer cells over expressing TOX3 followed by Pathway analysis showed that TOX3 Overexpression mainly affected the Interferon Signaling Pathway. TOX3 up regulation induced the expression of several genes with a gamma interferon activation site (GAS......), e.g. STAT1. In vitro functional studies showed that TOX3 was able to bind to the GAS-sequence located at the STAT1 promoter. siRNA mediated knockdown of TOX3 in RT4 bladder cancer cells decreased STAT1 expression suggesting a direct impact of TOX3 on STAT1. Immunoprecipitation of TOX3 over...

  10. Sex-specific hormone receptors in urothelial carcinomas of the human urinary bladder: a comparative analysis of clinicopathological features and survival outcomes according to receptor expression.

    Science.gov (United States)

    Tuygun, Can; Kankaya, Duygu; Imamoglu, Abdurrahim; Sertcelik, Ayse; Zengin, Kursad; Oktay, Murat; Sertcelik, Nurettin

    2011-01-01

    To investigate the expression of sex-specific hormone receptors in normal bladder urothelium and urothelial carcinomas (UCs) of the bladder, and to analyze clinicopathological features and survival outcomes according to receptor expression. We evaluated the clinical data and tumor specimens of 139 patients with bladder cancer (BC). In addition, 72 samples of normal urothelium were included. Immunohistochemistry was performed using streptavidin-biotin peroxidase method, a monoclonal androgen receptor (AR), and an estrogen receptor-β (ERβ) antibody on paraffin-embedded tissue sections. Expression levels of each receptor were assessed by evaluating 500 tumor cells for each case and the percentage of positively-stained nuclei was recorded. None of the 58 male control cases showed any AR and ERβ expression. Five (35, 71%) of the 14 female control cases expressed ERβ. Of the 139 patients with UCs, 71 (51, 07%) expressed AR (62 male vs. 9 female; P = 0.413) and 44 (31, 65%) (39 male vs. 5 female; P = 0.402) showed ERβ expression (P receptors alone cannot be responsible for gender differences in BC rates because they were expressed in similar rates in both sexes. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Novel robust biomarkers for human bladder cancer based on activation of intracellular signaling pathways

    OpenAIRE

    Lezhnina, Ksenia; Kovalchuk, Olga; Zhavoronkov, Alexander A.; Korzinkin, Mikhail B.; Zabolotneva, Anastasia A.; Shegay, Peter V.; Sokov, Dmitry G.; Gaifullin, Nurshat M.; Rusakov, Igor G.; Aliper, Alexander M.; Roumiantsev, Sergey A.; Alekseev, Boris Y.; Borisov, Nikolay M.; Buzdin, Anton A.

    2014-01-01

    We recently proposed a new bioinformatic algorithm called OncoFinder for quantifying the activation of intracellular signaling pathways. It was proved advantageous for minimizing errors of high-throughput gene expression analyses and showed strong potential for identifying new biomarkers. Here, for the first time, we applied OncoFinder for normal and cancerous tissues of the human bladder to identify biomarkers of bladder cancer. Using Illumina HT12v4 microarrays, we profiled gene expression ...

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    Bladder cancer is among the most prevalent malignancies, and is characterised by frequent tumour recurrences and localised inflammation, which may promote tissue invasion and metastasis. Microarray analysis was used to compare gene expression in normal bladder urothelium with that in tumours...... at different stages of progression. The innate immune response gene, interferon-stimulated gene 15 kDa (ISG15, GIP2), was highly expressed at all stages of bladder cancer as compared to normal urothelium. Western blotting revealed a tumour-associated expression of ISG15 protein. ISG15 exhibited a stage...... component of bladder cancer-associated gene expression....

  13. Current status of tissue engineering applied to bladder reconstruction in humans.

    Science.gov (United States)

    Gasanz, C; Raventós, C; Morote, J

    2018-01-11

    Bladder reconstruction is performed to replace or expand the bladder. The intestine is used in standard clinical practice for tissue in this procedure. The complications of bladder reconstruction range from those of intestinal resection to those resulting from the continuous contact of urine with tissue not prepared for this contact. In this article, we describe and classify the various biomaterials and cell cultures used in bladder tissue engineering and reviews the studies performed with humans. We conducted a review of literature published in the PubMed database between 1950 and 2017, following the principles of the PRISM declaration. Numerous in vitro and animal model studies have been conducted, but only 18 experiments have been performed with humans, with a total of 169 patients. The current evidence suggests that an acellular matrix, a synthetic polymer with urothelial and autologous smooth muscle cells attached in vitro or stem cells would be the most practical approach for experimental bladder reconstruction. Bladder replacement or expansion without using intestinal tissue is still a challenge, despite progress in the manufacture of biomaterials and the development of cell therapy. Well-designed studies with large numbers of patients and long follow-up times are needed to establish an effective clinical translation and standardisation of the check-up functional tests. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Comparative immunohistochemical characterization of interstitial cells in the urinary bladder of human, guinea pig and pig.

    Science.gov (United States)

    Steiner, Clara; Gevaert, Thomas; Ganzer, Roman; De Ridder, Dirk; Neuhaus, Jochen

    2018-05-01

    Interstitial cells (ICs) are thought to play a functional role in urinary bladder. Animal models are commonly used to elucidate bladder physiology and pathophysiology. However, inter-species comparative studies on ICs are rare. We therefore analyzed ICs and their distribution in the upper lamina propria (ULP), the deeper lamina propria (DLP) and the detrusor muscular layer (DET) of human, guinea pig (GP) and pig. Paraffin slices were examined by immunohistochemistry and 3D confocal immunofluorescence of the mesenchymal intermediate filament vimentin (VIM), alpha-smooth muscle actin (αSMA), platelet-derived growth factor receptor alpha (PDGFRα) and transient receptor potential cation channel A1 (TRPA1). Image stacks were processed for analysis using Huygens software; quantitative analysis was performed with Fiji macros. ICs were identified by immunoreactivity for VIM (excluding blood vessels). In all species ≥ 75% of ULP ICs were VIM + /PDGFRα + and ≥ 90% were VIM + /TRPA1 + . In human and pig ≥ 74% of ULP ICs were VIM + /αSMA + , while in GP the percentage differed significantly with only 37% VIM + /αSMA + ICs. Additionally, over 90% of αSMA + ICs were also TRPA1 + and PDGFRα + in human, GP and pig. In all three species, TRPA1 + and PDGFRα + ICs point to an active role for these cells in bladder physiology, regarding afferent signaling processes and signal modification. We hypothesize that decline in αSMA-positivity in GP reflects adaptation of bladder histology to smaller bladder size. In our experiments, pig bladder proved to be highly comparable to human urinary bladder and seems to provide safer interpretation of experimental findings than GP.

  15. E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells

    OpenAIRE

    Lee, Hyun-Wook; Park, Sung-Hyun; Weng, Mao-wen; Wang, Hsiang-Tsui; Huang, William C.; Lepor, Herbert; Wu, Xue-Ru; Chen, Lung-Chi; Tang, Moon-shong

    2018-01-01

    Significance E-cigarette smoke (ECS) delivers nicotine through aerosols without burning tobacco. ECS is promoted as noncarcinogenic. We found that ECS induces DNA damage in mouse lung, bladder, and heart and reduces DNA-repair functions and proteins in lung. Nicotine and its nitrosation product 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone can cause the same effects as ECS and enhance mutations and tumorigenic cell transformation in cultured human lung and bladder cells. These results indica...

  16. Basic bladder neurophysiology.

    Science.gov (United States)

    Clemens, J Quentin

    2010-11-01

    Maintenance of normal lower urinary tract function is a complex process that requires coordination between the central nervous system and the autonomic and somatic components of the peripheral nervous system. This article provides an overview of the basic principles that are recognized to regulate normal urine storage and micturition, including bladder biomechanics, relevant neuroanatomy, neural control of lower urinary tract function, and the pharmacologic processes that translate the neural signals into functional results. Finally, the emerging role of the urothelium as a sensory structure is discussed. Copyright © 2010 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Júlio Santos

    2014-12-01

    Full Text Available Bladder cancer is a significant health problem in rural areas of Africa and the Middle East where Schistosoma haematobium is prevalent, supporting an association between malignant transformation and infection by this blood fluke. Nevertheless, the molecular mechanisms linking these events are poorly understood. Bladder cancers in infected populations are generally diagnosed at a late stage since there is a lack of non-invasive diagnostic tools, hence enforcing the need for early carcinogenesis markers.Forty-three formalin-fixed paraffin-embedded bladder biopsies of S. haematobium-infected patients, consisting of bladder tumours, tumour adjacent mucosa and pre-malignant/malignant urothelial lesions, were screened for bladder cancer biomarkers. These included the oncoprotein p53, the tumour proliferation rate (Ki-67>17%, cell-surface cancer-associated glycan sialyl-Tn (sTn and sialyl-Lewisa/x (sLea/sLex, involved in immune escape and metastasis. Bladder tumours of non-S. haematobium etiology and normal urothelium were used as controls. S. haematobium-associated benign/pre-malignant lesions present alterations in p53 and sLex that were also found in bladder tumors. Similar results were observed in non-S. haematobium associated tumours, irrespectively of their histological nature, denoting some common molecular pathways. In addition, most benign/pre-malignant lesions also expressed sLea. However, proliferative phenotypes were more prevalent in lesions adjacent to bladder tumors while sLea was characteristic of sole benign/pre-malignant lesions, suggesting it may be a biomarker of early carcionogenesis associated with the parasite. A correlation was observed between the frequency of the biomarkers in the tumor and adjacent mucosa, with the exception of Ki-67. Most S. haematobium eggs embedded in the urothelium were also positive for sLea and sLex. Reinforcing the pathologic nature of the studied biomarkers, none was observed in the healthy urothelium

  18. Optical coherence tomography in diagnostics of precancer and cancer of human bladder

    Science.gov (United States)

    Zagaynova, Elena V.; Streltsova, Olga S.; Gladkova, Natalia D.; Shakhova, Natalia M.; Feldchtein, Felix I.; Kamensky, Vladislav A.; Gelikonov, Grigory V.; Snopova, Ludmila B.; Donchenko, Ekaterina V.

    2004-07-01

    Our goal was statistical assessment of the in vivo cystoscopic optical coherence tomography (OCT) ability to detect neoplasia in human urinary bladder. We analyzed major reasons of false positive and false negative image recognition results. Optical coherence tomography was performed to image the bladder during cystoscopy. The study enrolled 63 patients with suspicion for bladder cancer and scheduled for cystoscopy. The diagnosis was established by histopathology examination of a biopsy. Each biopsy site was examined by OCT. Benign conditions were diagnosed for 31 patients, and dysplasia or carcinoma were diagnosed for 32 patients. Six physicians blinded to all clinical data participated in the dichotomy recognition (malignant or benign) of the OCT images. 98% sensitivity and 72% specificity for the OCT recognition of dysplastic/malignant versus benign/reactive conditions of the bladder are demonstrated. Total error rate was 14.8%. The interobserver agreement multi-rater kappa coefficient is 0.80. The superficial and invasive bladder cancer and high-grade dysplasia were recognized with minimum error rate ranging from 0 to 3.3%. High sensitivity and good specificity of the OCT method in the diagnostics of bladder neoplasia makes OCT a promising complementary cystoscopic technique for non-invasive evaluation of zones suspicious for high-grade dysplasia and cancer.

  19. Co-cultures provide a new tool to probe communication between adult sensory neurons and urothelium.

    Science.gov (United States)

    O'Mullane, Lauren M; Keast, Janet R; Osborne, Peregrine B

    2013-08-01

    Recent evidence suggests that the urothelium functions as a sensory transducer of chemical, mechanical or thermal stimuli and signals to nerve terminals and other cells in the bladder wall. The cellular and molecular basis of neuro-urothelial communication is not easily studied in the intact bladder. This led us to establish a method of co-culturing dorsal root ganglion sensory neurons and bladder urothelial cells. Sensory neurons and urothelial cells obtained from dorsal root ganglia and bladders dissected from adult female Sprague-Dawley® rats were isolated by enzyme treatment and mechanical dissociation. They were plated together or separately on collagen coated substrate and cultured in keratinocyte medium for 48 to 72 hours. Retrograde tracer labeling was performed to identify bladder afferents used for functional testing. Neurite growth and complexity in neurons co-cultured with urothelial cells was increased relative to that in neuronal monocultures. The growth promoting effect of urothelial cells was reduced by the tyrosine kinase inhibitor K252a but upstream inhibition of nerve growth factor signaling with TrkA-Fc had no effect. Fura-2 calcium imaging of urothelial cells showed responses to adenosine triphosphate (100 μM) and activation of TRPV4 (4α-PDD, 10 μM) but not TRPV1 (capsaicin, 1 μM), TRPV3 (farnesyl pyrophosphate, 1 μM) or TRPA1 (mustard oil, 100 μM). In contrast, co-cultured neurons were activated by all agonists except farnesyl pyrophosphate. Co-culturing provides a new methodology for investigating neuro-urothelial interactions in animal models of urological conditions. Results suggest that neuronal properties are maintained in the presence of urothelium and neurite growth is potentiated by a nerve growth factor independent mechanism. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  20. Characterization of intracellular inclusions in the urothelium of mice exposed to inorganic arsenic.

    Science.gov (United States)

    Dodmane, Puttappa R; Arnold, Lora L; Muirhead, David E; Suzuki, Shugo; Yokohira, Masanao; Pennington, Karen L; Dave, Bhavana J; Lu, Xiufen; Le, X Chris; Cohen, Samuel M

    2014-01-01

    Inorganic arsenic (iAs) is a known human carcinogen at high exposures, increasing the incidences of urinary bladder, skin, and lung cancers. In most mammalian species, ingested iAs is excreted mainly through urine primarily as dimethylarsinic acid (DMA(V)). In wild-type (WT) mice, iAs, DMA(V), and dimethylarsinous acid (DMA(III)) exposures induce formation of intramitochondrial urothelial inclusions. Arsenite (iAs(III)) also induced intranuclear inclusions in arsenic (+3 oxidation state) methyltransferase knockout (As3mt KO) mice. The arsenic-induced formation of inclusions in the mouse urothelium was dose and time dependent. The inclusions do not occur in iAs-treated rats and do not appear to be related to arsenic-induced urothelial cytotoxicity. Similar inclusions in exfoliated urothelial cells from humans exposed to iAs have been incorrectly identified as micronuclei. We have characterized the urothelial inclusions using transmission electron microscopy (TEM), DNA-specific 4',6-diamidino-2-phenylindole (DAPI), and non-DNA-specific Giemsa staining and determined the arsenical content. The mouse inclusions stained with Giemsa but not with the DAPI stain. Analysis of urothelial mitochondrial- and nuclear-enriched fractions isolated from WT (C57BL/6) and As3mt KO mice exposed to arsenate (iAs(V)) for 4 weeks showed higher levels of iAs(V) in the treated groups. iAs(III) was the major arsenical present in the enriched nuclear fraction from iAs(V)-treated As3mt KO mice. In conclusion, the urothelial cell inclusions induced by arsenicals appear to serve as a detoxifying sequestration mechanism similar to other metals, and they do not represent micronuclei.

  1. Bilateral tumors of the upper urothelium

    Directory of Open Access Journals (Sweden)

    Đokić Milan

    2006-01-01

    Full Text Available Introduction: The incidence of tumors of the upper urothelium is high in our country, apart from their relation to specific regions (BEN and PBEN and their frequent bilateralism. Bilateral forms are present in significant percentage and are followed, in most cases, by renal failure, which speaks in favor of conservative surgery, if possible. Objective: The aim of the study was to present epidemiological, pathoanatomical and clinical characteristics of bilateral tumors of the upper urothelium and evaluate the Results of their treatment. Method: Our retrospective study analyzed 12 patients with bilateral tumors of the upper urothelium who were treated in the period from 1992 to 1996, according to their epidemiological, clinical, pathoanatomical and pathohistological characteristics, type of surgical treatment and relevant success. Results: In the observed period, bilateral tumors of the upper urothelium were found in 8.2% of our patients. In the group of 12 patients, 5 females and 7 males, 11 cases were from the region of Balkan Endemic Nephropathy (BEN. Renal failure was recorded in high percentage (66%. Radical surgical treatment - total nephroureterectomy was performed in 9 kidney units, and conservative operation in 15 units. Relapse significantly depended on tumor stage and grade, not on type of surgical treatment in the majority of cases. Five-year survival was 58.33%; major cause of death was associated with further evolution of tumor, recurrence and tumor dissemination, respectively, while renal failure complications were the cause of death in one case. Conclusion: The success of treatment mainly depends on tumor stage and grade and not on type of surgical Method in conservative treatment, but renal failure and its complications are an important risk factor in these patients.

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

    International Nuclear Information System (INIS)

    Egerod, Frederikke Lihme; Bartels, Annette; Fristrup, Niels; Borre, Michael; Ørntoft, Torben F; Oleksiewicz, Martin B; Brünner, Nils; Dyrskjøt, Lars

    2009-01-01

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

  3. Three-dimensional organoid culture reveals involvement of Wnt/β-catenin pathway in proliferation of bladder cancer cells.

    Science.gov (United States)

    Yoshida, Takahiro; Sopko, Nikolai A; Kates, Max; Liu, Xiaopu; Joice, Gregory; McConkey, David J; Bivalacqua, Trinity J

    2018-02-16

    There has been increasing awareness of the importance of three-dimensional culture of cancer cells. Tumor cells growing as multicellular spheroids in three-dimensional culture, alternatively called organoids, are widely believed to more closely mimic solid tumors in situ . Previous studies concluded that the Wnt/β-catenin pathway is required for regeneration of the normal urothelium after injury and that β-catenin is upregulated in human bladder cancers, but no clear evidence has been advanced to support the idea that the Wnt/β-catenin pathway is directly involved in deregulated proliferation and the other malignant characteristics of bladder cancer cells. Here we report that the Wnt/β-catenin pathway activator, CHIR99021, promoted proliferation of established human bladder cancer cell lines when they were grown in organoid culture but not when they were grown in conventional adherent cultures. CHIR99021 activated Wnt/β-catenin pathway in bladder cancer cell lines in organoid culture. CHIR99021 also stimulated proliferation and the Wnt/b-catenin pathway in primary human bladder cancer organoids. RNAi-mediated knockdown of β-catenin blocked growth of organoids. The effects of CHIR99021 were associated with decreased expression of the urothelial terminal differentiation marker, cytokeratin 20. Our data suggest that the Wnt/β-catenin pathway is required for the proliferation of bladder cancer cells in three-dimensional organoid culture and provide a concrete example of why organoid culture is important for cancer research.

  4. p16 expression is not associated with human papillomavirus in urinary bladder squamous cell carcinoma.

    Science.gov (United States)

    Alexander, Riley E; Hu, Yingchuan; Kum, Jennifer B; Montironi, Rodolfo; Lopez-Beltran, Antonio; Maclennan, Gregory T; Idrees, Muhammad T; Emerson, Robert E; Ulbright, Thomas M; Grignon, David G; Eble, John N; Cheng, Liang

    2012-11-01

    Squamous cell carcinoma of the urinary bladder is unusual and of unknown etiology. There is a well-established association between human papillomavirus (HPV) infection and the development of cervical and head/neck squamous cell carcinomas. However, the role of HPV in the pathogenesis of squamous cell carcinoma of the urinary bladder is uncertain. The purposes of this study were to investigate the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy. In all, 42 cases of squamous cell carcinoma of the urinary bladder and 27 cases of urothelial carcinoma with squamous differentiation were investigated. HPV infection was analyzed by both in situ hybridization at the DNA level and immunohistochemistry at the protein level. p16 protein expression was analyzed by immunohistochemistry. HPV DNA and protein were not detected in 42 cases of squamous cell carcinoma (0%, 0/42) or 27 cases of urothelial carcinoma with squamous differentiation (0%, 0/15). p16 expression was detected in 13 cases (31%, 13/42) of squamous cell carcinoma and 9 cases (33%, 9/27) of urothelial carcinoma with squamous differentiation. There was no correlation between p16 expression and the presence of HPV infection in squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation. Our data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. p16 expression should not be used as a surrogate marker for evidence of HVP infection in either squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HVP DNA nor protein is detectable in these neoplasms.

  5. Primary signet cell adenocarcinoma of bladder

    Directory of Open Access Journals (Sweden)

    Prateek Kinra

    2017-01-01

    Full Text Available Primary signet cell cancer of the urinary bladder is a relatively rare entity. Since there is no mucinous epithelium in the bladder, It is proposed that the tumor arises from metaplastic urothelium. Two thirds of the tumours are mucin secreting, in most of which the site of the deposition is either extracellular or intracellular displacing the nucleus to a peripheral crescent, giving the cells a signet ring appearance. The tumours are most often infiltrative and diffusely involving the majority of the bladder akin to its name sake in stomach. It is essential to distinguish this carcinoma from gastrointestinal metastases as different therapeutic strategies are often necessary.

  6. Muscarinic receptor subtypes in porcine detrusor: comparison with humans and regulation by bladder augmentation

    NARCIS (Netherlands)

    Goepel, M.; Gronewald, A.; Krege, S.; Michel, M. C.

    1998-01-01

    The properties of muscarinic acetylcholine receptors of porcine and human bladder detrusor were compared in radioligand binding studies using [3H]quinuclidinylbenzylate as the radioligand. The receptor affinity for the radioligand and the density of muscarinic receptors was similar in male and

  7. CDC91L1 (PIG-U) is a newly discovered oncogene in human bladder cancer.

    NARCIS (Netherlands)

    Guo, Z.; Linn, J.F.; Wu, G.; Anzick, S.L.; Eisenberger, C.F.; Halachmi, S.; Cohen, Y.; Fomenkov, A.; Hoque, M.O.; Okami, K.; Steiner, G.; Engles, J.M.; Osada, M.; Moon, C.; Ratovitski, E.; Trent, J.M.; Meltzer, P.S.; Westra, W.H.; Kiemeney, L.A.L.M.; Schoenberg, M.P.; Sidransky, D.; Trink, B.

    2004-01-01

    Genomic amplification at 20q11-13 is a common event in human cancers. We isolated a germline translocation breakpoint at 20q11 from a bladder cancer patient. We identified CDC91L1, the gene encoding CDC91L1 (also called phosphatidylinositol glycan class U (PIG-U), a transamidase complex unit in the

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    and identified by peptide mass fingerprinting using mass spectrometry and database search. We found most extensive and reproducible down-regulation of NADP dependent isocitrate dehydrogenase cytoplasmic (IDPc) and peroxiredoxin-II (Prx-II), in poorly differentiated T24 compared to well-differentiated RT4 bladder...... cancer cell line. Subsequent Western blotting analysis of human biopsy samples from bladder cancer patient revealed significant loss of IDPc and Prx-II in more advance tumor samples, in agreement with data on cell lines. These results suggest that loss of IDPc and Prx-II during tumor development may...

  9. Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer.

    Science.gov (United States)

    Weber, Lea; Schulz, Wolfgang A; Philippou, Stathis; Eckardt, Josephine; Ubrig, Burkhard; Hoffmann, Michéle J; Tannapfel, Andrea; Kalbe, Benjamin; Gisselmann, Günter; Hatt, Hanns

    2018-01-01

    Olfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca 2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer.

  10. Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Lea Weber

    2018-05-01

    Full Text Available Olfactory receptors (ORs are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer.

  11. mTORC2 activation is regulated by the urokinase receptor (uPAR) in bladder cancer.

    Science.gov (United States)

    Hau, Andrew M; Leivo, Mariah Z; Gilder, Andrew S; Hu, Jing-Jing; Gonias, Steven L; Hansel, Donna E

    2017-01-01

    Mammalian target of rapamycin complex 2 (mTORC2) has been identified as a major regulator of bladder cancer cell migration and invasion. Upstream pathways that mediate mTORC2 activation remain poorly defined. Urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored membrane protein and known activator of cell-signaling. We identified increased uPAR expression in 94% of invasive human bladder cancers and in 54-71% of non-invasive bladder cancers, depending on grade. Normal urothelium was uPAR-immunonegative. Analysis of publicly available datasets identified uPAR gene amplification or mRNA upregulation in a subset of bladder cancer patients with reduced overall survival. Using biochemical approaches, we showed that uPAR activates mTORC2 in bladder cancer cells. Highly invasive bladder cancer cell lines, including T24, J82 and UM-UC-3 cells, showed increased uPAR mRNA expression and protein levels compared with the less aggressive cell lines, UROtsa and RT4. uPAR gene-silencing significantly reduced phosphorylation of Serine-473 in Akt, an mTORC2 target. uPAR gene-silencing also reduced bladder cancer cell migration and Matrigel invasion. S473 phosphorylation was observed by immunohistochemistry in human bladder cancers only when the tumors expressed high levels of uPAR. S473 phosphorylation was not controlled by uPAR in bladder cancer cell lines that are PTEN-negative; however, this result probably did not reflect altered mTORC2 regulation. Instead, PTEN deficiency de-repressed alternative kinases that phosphorylate S473. Our results suggest that uPAR and mTORC2 are components of a single cell-signaling pathway. Targeting uPAR or mTORC2 may be beneficial in patients with bladder cancer. Copyright © 2016. Published by Elsevier Inc.

  12. METABOLISM AND DNA ADDUCT FORMATION OF 2-ACETYLAMINOFLUORENE BY BLADDER EXPLANTS FROM HUMAN, DOG, MONKEY, HAMSTER AND RAT

    Science.gov (United States)

    It is concluded that bladder explants of the human, dog, monkey, hamster, and rat metabolize AAF mainly to ring-hydroxylated products, but also form small amounts of the proximate carcinogenic metabolite N-hydroxy-AAF. Neither the overall binding of AAF to bladder DNA, nor the fo...

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

    Science.gov (United States)

    Memon, Ashfaque A; Chang, Jong W; Oh, Bong R; Yoo, Yung J

    2005-01-01

    Comparative proteome analysis was performed between RT4 (grade-1) and T24 (grade-3) bladder cancer cell lines, in an attempt to identify differentially expressed proteins during bladder cancer progression. Among those relatively abundant proteins, seven spots changed more than two-fold reproducibly and identified by peptide mass fingerprinting using mass spectrometry and database search. We found most extensive and reproducible down-regulation of NADP dependent isocitrate dehydrogenase cytoplasmic (IDPc) and peroxiredoxin-II (Prx-II), in poorly differentiated T24 compared to well-differentiated RT4 bladder cancer cell line. Subsequent Western blotting analysis of human biopsy samples from bladder cancer patient revealed significant loss of IDPc and Prx-II in more advance tumor samples, in agreement with data on cell lines. These results suggest that loss of IDPc and Prx-II during tumor development may involve in tumor progression and metastasis. However, additional investigations are needed on large number of human samples to further verify these findings.

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

    Science.gov (United States)

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

    1996-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Xia Zhang

    2015-10-01

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

  16. Biomarker in Cisplatin-Based Chemotherapy for Urinary Bladder Cancer.

    Science.gov (United States)

    Ecke, Thorsten H

    2015-01-01

    The treatment of metastasized bladder cancer has been evolving during recent years. Cisplatin based chemotherapy combinations are still gold standard in the treatment of advanced and metastasized bladder cancer. But new therapies are approaching. Based to this fact biological markers will become more important for decisions in bladder cancer treatment. A systematic MEDLINE search of the key words "cisplatin", "bladder cancer", "DNA marker", "protein marker", "methylation biomarker", "predictive marker", "prognostic marker" has been made. This review aims to highlight the most relevant clinical and experimental studies investigating markers for metastasized transitional carcinoma of the urothelium treated by cisplatin based regimens.

  17. Inhalation of tobacco smoke induces increased proliferation of urinary bladder epithelium and endothelium in female C57BL/6 mice

    International Nuclear Information System (INIS)

    Ohnishi, Takamasa; Arnold, Lora L.; He, Jun; Clark, Nicole M.; Kawasaki, Shin; Rennard, Stephen I.; Boyer, Craig W.; Cohen, Samuel M.

    2007-01-01

    Cigarette smoking is the major environmental risk factor for bladder cancer in humans. Aromatic amines, potent DNA-reactive bladder carcinogens present in cigarette smoke, contribute significantly. However, increased cell proliferation, caused by direct mitogenesis or in response to cytotoxicity, may also play a role since urothelial hyperplasia has been observed in human cigarette smokers. We examined the urothelial effects of cigarette smoke (whole body inhalation exposure (Teague) system) in female C57BL/6 mice at various times in two studies, including reversibility evaluations. In both studies, no urothelial hyperplasia was observed by light microscopy in any group. However, in study 1, the Ki-67 labeling index (LI) of the urothelium was significantly increased in the smoke exposed group compared to controls through 3 months, but was not present at 6, 9 or 12 months even with continued exposures. In the groups that discontinued smoke exposure, it returned to the same levels as controls or lower. In study 2, the bromodeoxyuridine LI was similar to controls on day 1 but significantly increased at 5 days in the smoke exposed group. In the group that discontinued smoke exposure for 2 days, the LI was increased compared to controls but not significantly. Superficial urothelial cell cytotoxicity and necrosis were detectable by scanning electron microscopy at 5 days. Changes in LI of submucosal endothelial cells generally followed those of the urothelium and effects were reversible upon cessation of exposure. The increased urothelial proliferation appeared to be due to superficial cell cytotoxicity with consequent regeneration

  18. Pumpkin Seed Oil Extracted From Cucurbita maxima Improves Urinary Disorder in Human Overactive Bladder

    Directory of Open Access Journals (Sweden)

    Mie Nishimura

    2014-01-01

    Full Text Available The pumpkin seed oil obtained from Cucurbita pepo has been shown to be useful for the treatment of nocturia in patients with urinal disorders in several western countries. In this study, we evaluated the effect of the pumpkin seed oil from Cucurbita maxima on urinary dysfunction in human overactive bladder (OAB. Forty-five subjects were enrolled in this study. An extract of pumpkin seed oil from C. maxima (10 g of oil/day was orally administrated for 12 weeks. After 6 and 12 weeks, urinary function was evaluated using Overactive Bladder Symptom Score (OABSS. Pumpkin seed oil from C. maxima significantly reduced the degree of OABSS in the subjects. The results from our study suggest that pumpkin seed oil extracts from C. maxima as well as from C. pepo are effective for urinary disorders such as OAB in humans.

  19. Pumpkin Seed Oil Extracted From Cucurbita maxima Improves Urinary Disorder in Human Overactive Bladder.

    Science.gov (United States)

    Nishimura, Mie; Ohkawara, Tatsuya; Sato, Hiroji; Takeda, Hiroshi; Nishihira, Jun

    2014-01-01

    The pumpkin seed oil obtained from Cucurbita pepo has been shown to be useful for the treatment of nocturia in patients with urinal disorders in several western countries. In this study, we evaluated the effect of the pumpkin seed oil from Cucurbita maxima on urinary dysfunction in human overactive bladder (OAB). Forty-five subjects were enrolled in this study. An extract of pumpkin seed oil from C. maxima (10 g of oil/day) was orally administrated for 12 weeks. After 6 and 12 weeks, urinary function was evaluated using Overactive Bladder Symptom Score (OABSS). Pumpkin seed oil from C. maxima significantly reduced the degree of OABSS in the subjects. The results from our study suggest that pumpkin seed oil extracts from C. maxima as well as from C. pepo are effective for urinary disorders such as OAB in humans.

  20. Pumpkin Seed Oil Extracted From Cucurbita maxima Improves Urinary Disorder in Human Overactive Bladder

    Science.gov (United States)

    Nishimura, Mie; Ohkawara, Tatsuya; Sato, Hiroji; Takeda, Hiroshi; Nishihira, Jun

    2014-01-01

    The pumpkin seed oil obtained from Cucurbita pepo has been shown to be useful for the treatment of nocturia in patients with urinal disorders in several western countries. In this study, we evaluated the effect of the pumpkin seed oil from Cucurbita maxima on urinary dysfunction in human overactive bladder (OAB). Forty-five subjects were enrolled in this study. An extract of pumpkin seed oil from C. maxima (10 g of oil/day) was orally administrated for 12 weeks. After 6 and 12 weeks, urinary function was evaluated using Overactive Bladder Symptom Score (OABSS). Pumpkin seed oil from C. maxima significantly reduced the degree of OABSS in the subjects. The results from our study suggest that pumpkin seed oil extracts from C. maxima as well as from C. pepo are effective for urinary disorders such as OAB in humans. PMID:24872936

  1. Effects of arsenite on cell cycle progression in a human bladder cancer cell line

    International Nuclear Information System (INIS)

    Hernandez-Zavala, A.; Cordova, E.; Razo, L.M. del; Cebrian, M.E.; Garrido, E.

    2005-01-01

    Bladder cancer is one of the most important diseases associated with arsenic (As) exposure in view of its high prevalence and mortality rate. Experimental studies have shown that As exposure induces cell proliferation in the bladder of sodium arsenite (iAsIII) subchronically treated mice. However, there is little available information on its effects on the cell cycle of bladder cells. Thus, our purpose was to evaluate the effects of iAsIII on cell cycle progression and the response of p53 and p21 on the human-derived epithelial bladder cell line HT1197. iAsIII treatment (1-10 μM) for 24 h induced a dose-dependent increase in the proportion of cells in S-phase, which reached 65% at the highest dose. A progressive reduction in cell proliferation was also observed. BrdU was incorporated to cellular DNA in an interrupted form, suggesting an incomplete DNA synthesis. The time-course of iAsIII effects (10 μM) showed an increase in p53 protein content and a transient increase in p21 protein levels accompanying the changes in S-phase. These effects were correlated with iAs concentrations inside the cells, which were not able to metabolize inorganic arsenic. Our findings suggest that p21 was not able to block CDK2-cyclin E complex activity and was therefore unable to arrest cells in G1 allowing their progression into the S-phase. Further studies are needed to ascertain the mechanisms underlying the effects of iAsIII on the G1 to S phase transition in bladder cells

  2. Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Kruhøffer, Mogens; Andersen, Thomas Thykjær

    2004-01-01

    not only in CIS biopsies but also in sTCC, mTCC, and, remarkably, in histologically normal urothelium from bladders with CIS. Identification of this expression signature could provide guidance for the selection of therapy and follow-up regimen in patients with early stage bladder cancer....

  3. Receptor-targeted therapy of human experimental urinary bladder cancers with cytotoxic LH-RH analog AN-152 [AEZS- 108].

    Science.gov (United States)

    Szepeshazi, Karoly; Schally, Andrew V; Keller, Gunhild; Block, Norman L; Benten, Daniel; Halmos, Gabor; Szalontay, Luca; Vidaurre, Irving; Jaszberenyi, Miklos; Rick, Ferenc G

    2012-07-01

    Many bladder cancers progress to invasion with poor prognosis; new therapeutic methods are needed. We developed a cytotoxic LH-RH analog, AN-152 (AEZS-108) containing doxorubicin (DOX), for targeted therapy of cancers expressing LHRH receptors. We investigated the expression of LH-RH receptors in clinical bladder cancers and in HT-1376, J82, RT-4 and HT-1197 human bladder cancer lines. The effect of analog, AN-152, on growth of these tumor lines xenografted into nude mice was analyzed. Using molecular and functional assays, we also evaluated the differences between the effects of AN-152, and DOX alone. We demonstrated the expression of LH-RH receptors on 18 clinical bladder cancers by immunohistochemistry and on four human urinary bladder cancer lines HT-1376, J82, RT-4 and HT-1197 by Western blotting and binding assays. AN-152 powerfully inhibited growth of these bladder cancers in nude mice. AN-152 exerted greater effects than DOX and was less toxic. DOX activated strong multidrug resistance mechanisms in RT-4 and HT-1197 cancers, while AN-152 had no or less such effect. PCR assays and in vitro studies revealed differences in the action of AN-152 and DOX on the expression of genes involved in apoptosis. These results suggest that targeted cytotoxic LH-RH analog, AN-152 (AEZS- 108), should be examined for treatment of patients with LH-RH receptor positive invasive bladder cancers.

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

    Directory of Open Access Journals (Sweden)

    Liqun Zhou

    2013-10-01

    Full Text Available Kaempferol (Kae, a natural flavonoid, is widely distributed in fruits and vegetables. Previous studies have identified Kae as a possible cancer preventive and therapeutic agent. We found Kae to exhibit potent antiproliferation and anti-migration effects in human bladder cancer EJ cells. Kaempferol robustly induced apoptosis in EJ cells in a dose-dependent manner, as evidenced by increased cleavage of caspase-3. Furthermore, we found Kae-induced apoptosis in EJ cells to be associated with phosphatase and the tensin homolog deleted on the chromosome 10 (PTEN/PI3K/Akt pathway. Kae significantly increased PTEN and decreased Akt phosphorylation. Kae-induced apoptosis was partially attenuated in PTEN-knockdown cells. Our findings indicate that Kae could be an alternative medicine for bladder cancer, based on a PTEN activation mechanism.

  5. Enhanced urothelial expression of human chorionic gonadotropin beta (hCGβ) in bladder pain syndrome/interstitial cystitis (BPS/IC).

    Science.gov (United States)

    Schwalenberg, Thilo; Stolzenburg, Jens-Uwe; Ho, Thi Phuc; Mallock, Tobias; Hartenstein, Siegurd; Alexander, Henry; Zimmermann, Gerolf; Hohenfellner, Rudolf; Denzinger, Stefan; Burger, Maximilian; Horn, Lars-Christian; Neuhaus, Jochen

    2012-06-01

    Bladder pain syndrome/interstitial cystitis (BPS/IC) is associated with urothelial lesions. Pathomechanisms of urothelial damage and factors for urothelial restoration are unknown. hCG is a factor for cellular differentiation, angiogenesis and immune competence of the endometrium during pregnancy. Clinical observations demonstrate improvement of BPS/IC symptoms during pregnancy or during infertility treatment with hCG. Our research aims were to examine the expression of hCG and luteinizing hormone receptor (LHR) in the urothelium of BPS/IC patients and compare the levels of hCGβ with healthy controls. Bladder biopsies of BPS/IC (CLSM: n = 10; qPCR: n = 15); Tumour-free control tissue from cystectomies (n = 12). hCGα, hCGβ and LHR expression were examined by confocal laser scanning microscopy (CLSM), and hCGβ expression was quantified. hCGβ5 and hCGβ7 mRNA splice variants were quantified in real-time polymerase chain reaction. We found constitutive expression of hCGα, hCGβ and LHR in healthy controls. HCGβ was significantly upregulated in BPS/IC patients in CLSM. PCR analysis revealed higher levels of hCGβ7 than hCGβ5 in controls and BPS/IC patients. The constitutive expression of hCG and LHR speaks in favour for a functional signalling in urothelial cells without any association with either pregnancy or tumour. We show for the first time that hCGβ is upregulated in BPS/IC urothelium and that hCGβ7 is the dominant splice variant in those cells. Our findings imply a major role of hCG for urothelial integrity and a disturbance of hCG signalling in case of BPS/IC. We conclude that hCG could gain therapeutical relevance in the future.

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

    Science.gov (United States)

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

    2011-02-01

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

  7. Association of Human Development Index with global bladder, kidney, prostate and testis cancer incidence and mortality.

    Science.gov (United States)

    Greiman, Alyssa K; Rosoff, James S; Prasad, Sandip M

    2017-12-01

    To describe contemporary worldwide age-standardized incidence and mortality rates for bladder, kidney, prostate and testis cancer and their association with development. We obtained gender-specific, age-standardized incidence and mortality rates for 184 countries and 16 major world regions from the GLOBOCAN 2012 database. We compared the mortality-to-incidence ratios (MIRs) at national and regional levels in males and females, and assessed the association with socio-economic development using the 2014 United Nations Human Development Index (HDI). Age-standardized incidence rates were 2.9 (bladder) to 7.4 (testis) times higher for genitourinary malignancies in more developed countries compared with less developed countries. Age-standardized mortality rates were 1.5-2.2 times higher in more vs less developed countries for prostate, bladder and kidney cancer, with no variation in mortality rates observed in testis cancer. There was a strong inverse relationship between HDI and MIR in testis (regression coefficient 1.65, R 2 = 0.78), prostate (regression coefficient -1.56, R 2 = 0.85), kidney (regression coefficient -1.34, R 2 = 0.74), and bladder cancer (regression coefficient -1.01, R 2 = 0.80). While incidence and mortality rates for genitourinary cancers vary widely throughout the world, the MIR is highest in less developed countries for all four major genitourinary malignancies. Further research is needed to understand whether differences in comorbidities, exposures, time to diagnosis, access to healthcare, diagnostic techniques or treatment options explain the observed inequalities in genitourinary cancer outcomes. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

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

    International Nuclear Information System (INIS)

    Joshi, Bharat H; Leland, Pamela; Lababidi, Samir; Varrichio, Frederick; Puri, Raj K

    2014-01-01

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

  9. The role of TRPM8 in the Guinea-pig bladder-cooling reflex investigated using a novel TRPM8 antagonist.

    Science.gov (United States)

    Gardiner, Jennifer C; Kirkup, Anthony J; Curry, John; Humphreys, Sian; O'Regan, Paul; Postlethwaite, Michael; Young, Kimberley C; Kitching, Linda; Ethell, Brian T; Winpenny, David; McMurray, Gordon

    2014-10-05

    Patients with overactive bladder often exhibit abnormal bladder contractions in response to intravesical cold saline (positive ice-water test). The molecular entity involved in cold sensation within the urinary bladder is unknown, but a potential candidate is the ion channel, transient receptor potential (melastatin)-8 (TRPM8). The objective of the present study was to investigate the role of TRPM8 in a bladder-cooling reflex evoked in anaesthetised guinea-pigs that is comparable to the positive ice-water test seen in patients. Guinea-pig TRPM8 was cloned from L6 dorsal root ganglia (DRG) and expressed in HEK293 cells. Functional agonist- and cold-induced Ca2+ influx and electrophysiology assays were performed in these cells, and for comparison in HEK293 cells expressing human TRPM8, using a novel TRPM8 antagonist, the S-enantiomer of 1-phenylethyl 4-(benzyloxy)-3-methoxybenzyl (2-aminoethyl) carbamate hydrochloride (PBMC). Potency data from these assays was used to calculate intravenous infusion protocols for targeted plasma concentrations of PBMC in studies on micturition reflexes evoked by intravesical infusion of menthol or cold saline in anaesthetised guinea-pigs. Tissue expression of TRPM8 in guinea-pig bladder, urethra and in dorsal root ganglia neurones traced from the bladder was also investigated. TRPM8 mRNA and protein were detected in L6 dorsal root ganglia, bladder urothelium and smooth muscle. PBMC antagonised in vitro activation of human and guinea-pig TRPM8 and reversed menthol and cold-induced facilitation of the micturition reflex at plasma concentrations consistent with in vitro potencies. The present data suggest that the bladder-cooling reflex in the guinea-pig involves TRPM8. The potential significance of TRPM8 in bladder disease states deserves future investigation. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Roles of polyuria and hyperglycemia in bladder dysfunction in diabetes.

    Science.gov (United States)

    Xiao, Nan; Wang, Zhiping; Huang, Yexiang; Daneshgari, Firouz; Liu, Guiming

    2013-03-01

    Diabetes mellitus causes diabetic bladder dysfunction. We identified the pathogenic roles of polyuria and hyperglycemia in diabetic bladder dysfunction in rats. A total of 72 female Sprague-Dawley® rats were divided into 6 groups, including age matched controls, and rats with sham urinary diversion, urinary diversion, streptozotocin induced diabetes mellitus after sham urinary diversion, streptozotocin induced diabetes mellitus after urinary diversion and 5% sucrose induced diuresis after sham urinary diversion. Urinary diversion was performed by ureterovaginostomy 10 days before diabetes mellitus induction. Animals were evaluated 20 weeks after diabetes mellitus or diuresis induction. We measured 24-hour drinking and voiding volumes, and cystometry. Bladders were harvested to quantify smooth muscle, urothelium and collagen. We measured nitrotyrosine and Mn superoxide dismutase in the bladder. Diabetes and diuresis caused increases in drinking and voiding volume, and bladder weight. Bladder weight decreased in the urinary diversion group and the urinary diversion plus diabetes group. The intercontractile interval, voided volume and compliance increased in the diuresis and diabetes groups, decreased in the urinary diversion group and further decreased in the urinary diversion plus diabetes group. Total cross-sectional tissue, smooth muscle and urothelium areas increased in the diuresis and diabetes groups, and decreased in the urinary diversion and urinary diversion plus diabetes groups. As a percent of total tissue area, collagen decreased in the diuresis and diabetes groups, and increased in the urinary diversion and urinary diversion plus diabetes groups. Smooth muscle and urothelium decreased in the urinary diversion and urinary diversion plus diabetes groups. Nitrotyrosine and Mn superoxide dismutase increased in rats with diabetes and urinary diversion plus diabetes. Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative

  11. Gamma-Klotho exhibits multiple roles in tumor growth of human bladder cancer.

    Science.gov (United States)

    Hori, Shunta; Miyake, Makito; Tatsumi, Yoshihiro; Morizawa, Yosuke; Nakai, Yasushi; Onishi, Sayuri; Onishi, Kenta; Iida, Kota; Gotoh, Daisuke; Tanaka, Nobumichi; Fujimoto, Kiyohide

    2018-04-13

    Alpha-Klotho (KLα) and beta-Klotho (KLβ) have recently been reported to correlate with cancer prognosis in some malignancies and we previously reported the association between KLα, KLβ, and urothelial carcinoma of the bladder (UCB), indicating that KLβ acts as a tumor promoter. However, the association between gamma-Klotho (KLγ) and cancer prognosis remains unclear. In the present study, we evaluated the association between KLγ and UCB. To evaluate the effect of KLγ on human bladder cancer cell lines in vitro assays were performed. Exogenous KLγ increased the ability of human bladder cancer cells to proliferate, migrate, invade, form colonies, and provide anchorage-independent growth potential. In in vivo assays, eighteen mice bearing xenografts inoculated using UM-UC-3, were randomly divided into three groups and treated with a small interfering RNA (siRNA) by intratumoral administration once a week for four weeks. Knockdown of KLγ with siRNA led to a dramatic change in tumor growth and suggested that KLγ had effects on tumor growth, including promotion of cell proliferation, inhibition of apoptosis, and enhancement of the epithelial-mesenchymal transition. To confirm the study, human tissue samples were used and patients were divided into two groups according to KLγ expression level. High expression of KLγ was significantly associated with higher stage and grade cancer and the presence of lymphovascular invasion compared to patients with lower expression of KLγ. Our results suggest that KLγ plays an important role in tumor invasion and progression and these results may lead to the development of new therapies and diagnostic methods for UCB.

  12. Expression and function of K(V)2-containing channels in human urinary bladder smooth muscle.

    Science.gov (United States)

    Hristov, Kiril L; Chen, Muyan; Afeli, Serge A Y; Cheng, Qiuping; Rovner, Eric S; Petkov, Georgi V

    2012-06-01

    The functional role of the voltage-gated K(+) (K(V)) channels in human detrusor smooth muscle (DSM) is largely unexplored. Here, we provide molecular, electrophysiological, and functional evidence for the expression of K(V)2.1, K(V)2.2, and the electrically silent K(V)9.3 subunits in human DSM. Stromatoxin-1 (ScTx1), a selective inhibitor of K(V)2.1, K(V)2.2, and K(V)4.2 homotetrameric channels and of K(V)2.1/9.3 heterotetrameric channels, was used to examine the role of these channels in human DSM function. Human DSM tissues were obtained during open bladder surgeries from patients without a history of overactive bladder. Freshly isolated human DSM cells were studied using RT-PCR, immunocytochemistry, live-cell Ca(2+) imaging, and the perforated whole cell patch-clamp technique. Isometric DSM tension recordings of human DSM isolated strips were conducted using tissue baths. RT-PCR experiments showed mRNA expression of K(V)2.1, K(V)2.2, and K(V)9.3 (but not K(V)4.2) channel subunits in human isolated DSM cells. K(V)2.1 and K(V)2.2 protein expression was confirmed by Western blot analysis and immunocytochemistry. Perforated whole cell patch-clamp experiments revealed that ScTx1 (100 nM) inhibited the amplitude of the voltage step-induced K(V) current in freshly isolated human DSM cells. ScTx1 (100 nM) significantly increased the intracellular Ca(2+) level in DSM cells. In human DSM isolated strips, ScTx1 (100 nM) increased the spontaneous phasic contraction amplitude and muscle force, and enhanced the amplitude of the electrical field stimulation-induced contractions within the range of 3.5-30 Hz stimulation frequencies. These findings reveal that ScTx1-sensitive K(V)2-containing channels are key regulators of human DSM excitability and contractility and may represent new targets for pharmacological or genetic intervention for bladder dysfunction.

  13. Pumpkin Seed Oil Extracted From Cucurbita maxima Improves Urinary Disorder in Human Overactive Bladder

    OpenAIRE

    Nishimura, Mie; Ohkawara, Tatsuya; Sato, Hiroji; Takeda, Hiroshi; Nishihira, Jun

    2014-01-01

    The pumpkin seed oil obtained from Cucurbita pepo has been shown to be useful for the treatment of nocturia in patients with urinal disorders in several western countries. In this study, we evaluated the effect of the pumpkin seed oil from Cucurbita maxima on urinary dysfunction in human overactive bladder (OAB). Forty-five subjects were enrolled in this study. An extract of pumpkin seed oil from C. maxima (10 g of oil/day) was orally administrated for 12 weeks. After 6 and 12 weeks, urinary ...

  14. DIFFERENTIAL MODULATION OF CANCER-RELATED MOLECULAR NETWORKS IN HUMAN AND RAT URINARY BLADDER CELLS EXPOSED TO TRIVALENT ARSENICALS

    Science.gov (United States)

    Arsenic (As) is classified as a known human carcinogen with primary targets of urinary bladder (UB), skin and lung. The most prevalent source of As exposure in humans is drinking water contaminated with inorganic As (iAs), and millions of people worldwide are exposed to drinking ...

  15. Rat Urinary Bladder Carcinogenesis by Dual-Acting PPARα+γ Agonists

    Directory of Open Access Journals (Sweden)

    Martin B. Oleksiewicz

    2008-01-01

    Full Text Available Despite clinical promise, dual-acting activators of PPARα and γ (here termed PPARα+γ agonists have experienced high attrition rates in preclinical and early clinical development, due to toxicity. In some cases, discontinuation was due to carcinogenic effect in the rat urothelium, the epithelial layer lining the urinary bladder, ureters, and kidney pelvis. Chronic pharmacological activation of PPARα is invariably associated with cancer in rats and mice. Chronic pharmacological activation of PPARγ can in some cases also cause cancer in rats and mice. Urothelial cells coexpress PPARα as well as PPARγ, making it plausible that the urothelial carcinogenicity of PPARα+γ agonists may be caused by receptor-mediated effects (exaggerated pharmacology. Based on previously published mode of action data for the PPARα+γ agonist ragaglitazar, and the available literature about the role of PPARα and γ in rodent carcinogenesis, we propose a mode of action hypothesis for the carcinogenic effect of PPARα+γ agonists in the rat urothelium, which combines receptor-mediated and off-target cytotoxic effects. The proposed mode of action hypothesis is being explored in our laboratories, towards understanding the human relevance of the rat cancer findings, and developing rapid in vitro or short-term in vivo screening approaches to faciliate development of new dual-acting PPAR agonist compounds.

  16. Human Adipose Derived Stem Cells Induced Cell Apoptosis and S Phase Arrest in Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Xi Yu

    2015-01-01

    Full Text Available The aim of this study was to determine the effect of human adipose derived stem cells (ADSCs on the viability and apoptosis of human bladder cancer cells. EJ and T24 cells were cocultured with ADSCs or cultured with conditioned medium of ADSCs (ADSC-CM, respectively. The cell counting and colony formation assay showed ADSCs inhibited the proliferation of EJ and T24 cells. Cell viability assessment revealed that the secretions of ADSCs, in the form of conditioned medium, were able to decrease cancer cell viability. Wound-healing assay suggested ADSC-CM suppressed migration of T24 and EJ cells. Moreover, the results of the flow cytometry indicated that ADSC-CM was capable of inducing apoptosis of T24 cells and inducing S phase cell cycle arrest. Western blot revealed ADSC-CM increased the expression of cleaved caspase-3 and cleaved PARP, indicating that ADSC-CM induced apoptosis in a caspase-dependent way. PTEN/PI3K/Akt pathway and Bcl-2 family proteins were involved in the mechanism of this reaction. Our study indicated that ADSCs may provide a promising and practicable manner for bladder tumor therapy.

  17. Functional and Molecular Evidence for Kv7 Channel Subtypes in Human Detrusor from Patients with and without Bladder Outflow Obstruction

    DEFF Research Database (Denmark)

    Svalø, Julie; Sheykhzade, Majid; Nordling, Jørgen

    2015-01-01

    The aim of the study was to investigate whether Kv7 channels and their ancillary β-subunits, KCNE, are functionally expressed in the human urinary bladder. Kv7 channels were examined at the molecular level and by functional studies using RT-qPCR and myography, respectively. We found mRNA expressi...... between Kv7 channels and β-adrenoceptors in the human urinary bladder. The performed gene expression analysis combined with the organ bath studies imply that compounds that activate Kv7 channels could be useful for treatment of overactive bladder syndrome.......The aim of the study was to investigate whether Kv7 channels and their ancillary β-subunits, KCNE, are functionally expressed in the human urinary bladder. Kv7 channels were examined at the molecular level and by functional studies using RT-qPCR and myography, respectively. We found mRNA expression...... (activator of Kv7.1 channels, 10 μM) and ML213 (activator of Kv7.2, Kv7.4, Kv7.4/7.5 and Kv7.5 channels, 10 μM), reduced the tone of 1 μM carbachol pre-constricted bladder strips. XE991 (blocker of Kv7.1-7.5 channels, 10 μM) had opposing effects as it increased contractions achieved with 20 mM KPSS...

  18. Ketamine-induced bladder fibrosis involves epithelial-to-mesenchymal transition mediated by transforming growth factor-β1.

    Science.gov (United States)

    Wang, Junpeng; Chen, Yang; Gu, Di; Zhang, Guihao; Chen, Jiawei; Zhao, Jie; Wu, Peng

    2017-10-01

    Bladder wall fibrosis is a major complication of ketamine-induced cystitis (KC), but the underlying pathogenesis is poorly understood. The aim of the present study was to elucidate the mechanism of ketamine-induced fibrosis in association with epithelial-to-mesenchymal transition (EMT) mediated by transforming growth factor-β1 (TGF-β1). Sprague-Dawley rats were randomly distributed into four groups, which received saline, ketamine, ketamine combined with a TGF-β receptor inhibitor (SB-505124) for 16 wk, or 12 wk of ketamine and 4 wk of abstinence. In addition, the profibrotic effect of ketamine was confirmed in SV-40 immortalized human uroepithelial (SV-HUC-1) cells. The ketamine-treated rats displayed voiding dysfunction and decreased bladder compliance. Bladder fibrosis was accompanied by the appearance of a certain number of cells expressing both epithelial and mesenchymal markers, indicating that epithelial cells might undergo EMT upon ketamine administration. Meanwhile, the expression level of TGF-β1 was significantly upregulated in the urothelium of bladders in ketamine-treated rats. Treatment of SV-HUC-1 cells with ketamine increased the expression of TGF-β1 and EMT-inducing transcription factors, resulting in the downregulation of E-cadherin and upregulation of fibronectin and α-smooth muscle actin. Administration of SB-505124 inhibited EMT and fibrosis both in vitro and vivo. In addition, withdrawal from ketamine did not lead to recovery of bladder urinary function or decreased fibrosis. Taken together, our study shows for the first time that EMT might contribute to bladder fibrosis in KC. TGF-β1 may have an important role in bladder fibrogenesis via an EMT mechanism. Copyright © 2017 the American Physiological Society.

  19. Regorafenib Induces Apoptosis and Inhibits Metastatic Potential of Human Bladder Carcinoma Cells.

    Science.gov (United States)

    Hsu, Fei-Ting; Sun, Cho-Chin; Wu, Chia-Hsing; Lee, Yen-Ju; Chiang, Chih-Hung; Wang, Wei-Shu

    2017-09-01

    The aim of the present study was to verify the effects of regorafenib on apoptosis and metastatic potential in TSGH 8301 human bladder carcinoma cells in vitro. Cells were treated with different concentration of regorafenib for different periods of time. Effects of regorafenib on cell viability, apoptosis pathways, metastatic potential, and expression of metastatic and anti-apoptotic proteins were evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, flow cytometry, cell migration and invasion assay, and western blotting. We found regorafenib significantly reduced cell viability, cell migration and invasion, and expression of metastatic and anti-apoptotic proteins. In addition, regorafenib significantly induced accumulation of sub-G 1 phase cells, loss of mitochondrial membrane potential, and expression of active caspase-3 and caspase-8. These results show that regorafenib not only induces apoptosis, but also inhibits metastatic potential in bladder cancer TSGH 8301 cells in vitro. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  20. Differential repair of platinum-DNA adducts in human bladder and testicular tumor continuous cell lines

    International Nuclear Information System (INIS)

    Bedford, P.; Fichtinger-Schepman, A.M.; Shellard, S.A.; Walker, M.C.; Masters, J.R.; Hill, B.T.

    1988-01-01

    The formation and removal of four platinum-DNA adducts were immunochemically quantitated in cultured cells derived from a human bladder carcinoma cell line (RT112) and from two lines derived from germ cell tumors of the testis (833K and SUSA), following exposure in vitro to 16.7 microM (5 micrograms/ml) cisplatin. RT112 cells were least sensitive to the drug and were proficient in the repair of all four adducts, whereas SUSA cells, which were 5-fold more sensitive, were deficient in the repair of DNA-DNA intrastrand cross-links in the sequences pApG and pGpG. Despite expressing a similar sensitivity to SUSA cells, 833K cells were proficient in the repair of all four adducts, although less so than the RT112 bladder tumor cells. In addition, SUSA cells were unable to repair DNA-DNA interstrand cross-links whereas 50-85% of these lesions were removed in RT112 and 833K cells 24 h following drug exposure. It is possible that the inability of SuSa cells to repair platinated DNA may account for their hypersensitivity to cisplatin

  1. Labelling of anti-human bladder tumor chimeric antibody with 99Tcm and radioimmunoimaging of bladder carcinoma xenograft in nude mice

    International Nuclear Information System (INIS)

    Zhang Chunli; Wang Rongfu; Fu Zhanli; Bai Yin; Ding Yi; Yu Lizhang

    2003-01-01

    Objective: To study the in vitro immunoreactivity and in vivo tissue distribution, tumor targeting property of anti-human bladder tumor human-murine chimeric antibody (ch-BDI) labeled with 99 Tc m and to investigate its possibility for being used in guiding diagnosis and guiding therapy of bladder cancer. Methods: The ch-BDI was labeled with 99 Tc m by improved Schwarz method and the labeled antibody was purified by Sephadex G-50. Labeling yield and radiochemical purity were measured by paper chromatography. The immunoreactive fraction and association constant (K a ) were measured by Lindmo method and Scatchard analysis, respectively. 11.1 MBq (30 μg) 99 Tc m -ch-BDI was intravenously injected into nude mice bearing human bladder cancer xenografts in the right thigh and radioimmunoimaging (RII) was performed 2, 6, 20 and 24 h postinjection. The images were processed by region of interest (ROI) method to acquire the counts of whole body and the tumor and the counts ratios of tumor to contralateral normal tissue or to tissues of other non-tumor bearing organs. The mice were killed after 24 h postinjection imaging and tissue distribution was measured. %ID/g and target to nontarget (T/NT) ratios were calculated. Results: The labeling yield and radiochemical purity of 99 Tc m -ch-BDI were (66.5±7.3)% and >90%, respectively. The immunoreactive fraction was 76% and K a was 3.56 x 10 9 L/mol. RII showed that the tumor was clearly visualized 6 h postinjection and becoming clearer along with time prolonging. The radioactivity of whole body decreased rapidly with time, whereas the radioactivity of the tumor decreased slowly. The T/NT ratios was increased with time. Biodistribution results showed that tumor uptake was 17.4%ID/g 24 h postinjection. T/NT ratios were very high except for the kidney. T/NT ratios for brain, muscle, intestinal wall, bone and heart wall were 136.0, 55.1, 39.3, 29.7 and 27.9, respectively. Conclusion: 99 Tc m -ch-BDI exhibits excellent

  2. Roles of Polyuria and Hyperglycemia on Bladder Dysfunction in Diabetes

    Science.gov (United States)

    Xiao, Nan; Wang, Zhiping; Huang, Yexiang; Daneshgari, Firouz; Liu, Guiming

    2014-01-01

    Purpose Diabetes mellitus (DM) causes diabetic bladder dysfunction (DBD). We aimed to identify the pathogenic roles of polyuria and hyperglycemia on DBD in rats. Materials and Methods Seventy-two female Sprague-Dawley rats were divided: age-matched controls (control), sham urinary diversion (sham), urinary diversion (UD), streptozotocin-induced diabetes after sham UD (DM), streptozotocin-induced diabetes after UD (UD+DM), and 5% sucrose-induced diuresis after sham UD (DIU). UD was performed by ureterovaginostomy 10d before DM induction. Animals were evaluated 20 wks after DM or diuresis induction. We measured 24-hr drinking and voiding volumes and cystometry (CMG). Bladders were harvested for quantification of smooth muscle, urothelium, and collagen. We measured nitrotyrosine and manganese superoxide dismutase (MnSOD) in bladder. Results Diabetes and diuresis caused increases in drinking volume, voiding volume and bladder weight. Bladder weights decreased in the UD and UD+DM groups. Intercontractile intervals, voided volume, and compliance increased in the DIU and DM groups, decreased in the UD, and further decreased in the UD+DM group. The total cross-sectional tissue, smooth muscle and urothelium areas increased in the DIU and DM groups, and decreased in the UD and UD+DM groups. As percentages of total tissue area, collagen decreased in the DIU and DM groups, and increased in the UD and UD+DM groups, and smooth muscle and urothelium decreased in the UD and UD+DM groups. Nitrotyrosine and MnSOD increased in DM and UD+DM rats. Conclusions Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative stress in the bladder, which may play a pathogenic role in late stage DBD. PMID:22999997

  3. Imaging of urinary bladder tumors

    International Nuclear Information System (INIS)

    Hadjidekov, G.

    2015-01-01

    Full text: Primary bladder neoplasms account for 2%-6% of all tumors, with urinary bladder cancer ranked as the fourth most common cancer in males. Transitional cell carcinoma (TCC) is the most common subtype of urothelial tumour accounting for approximately 90% of all urothelial cancers. It is typically observed in men aged 50-70 years with history of smoking or occupational exposure to carcinogens. Most urothelial neoplasms are low-grade papillary tumors, with high incidence of recurrence, requires rigorous follow-up but have a relatively good prognosis. Other bladder neoplasm include squamous cell carcinoma accounts for 2%-15% mainly according to geographic location; adenocarcinoma - less than 2% /both occurring in the context of chronic bladder infection and irritation/; mesenchymal tumors in 5%, with the most common examples being rhabdomyosarcoma in children and leiomyosarcoma in adults. More rare mesenchymal tumors include paraganglioma, lymphoma, leiomyoma and solitary fibrous tumor which have no specific typical imaging findings to be differentiated. Multidetector computed tomography urography is an efficient tool for diagnosis and follow-up in patients with transitional cell carcinoma and it can be considered the primary radiologic method for detection, staging and assessment of the entire urothelium regarding the multicentric nature of TCC. MRI is rapidly expanding modality of choice especially in locally staging the tumor and in controversies. Accurate TNM staging is primordial in choosing treatment and prognosis for patients with bladder carcinoma. Correct interpretation and classification of the tumour is helpful for the urologists to determine further management in these cases. The learning objectives of the presentation are: to illustrate the spectrum of CT and MRI findings and to assess their clinical value in patients with transitional cell carcinoma and some other bladder neoplasm; to discuss the TNM staging based on the imaging findings; to be

  4. 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 ...

  5. Bladder Cancer

    Science.gov (United States)

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

  6. Pioglitazone and bladder cancer in human studies: Is it diabetes itself, diabetes drugs, flawed analyses or different ethnicities?

    Directory of Open Access Journals (Sweden)

    Chin-Hsiao Tseng

    2012-03-01

    Full Text Available This article reviews human observations on pioglitazone and bladder cancer risk. The PROspective pioglitAzone Clinical Trial In macroVascular Events trial showed an imbalance in bladder cancer between users of pioglitazone and placebo (14 versus six cases, p = 0.069. However, after excluding bladder cancer probably ascribed to other etiology, a blind assessment concluded that the imbalance might not be related to pioglitazone. Epidemiologic studies conducted in the United States and France using insurance databases independently suggested that pioglitazone use for >2 years might confer a 20%–40% higher risk. Another study evaluating bladder cancer risk in diabetic patients using the National Health Insurance in Taiwan did not find any incident bladder cancer case among 422 pioglitazone users for a follow-up of up to 3 years. Because observational studies may suffer from selection and information bias, and inadequate adjustment for confounders may inflate the estimated risk, causal inference from these studies should be interpreted with caution. While investigating cancer risk associated with a medication, indication bias should also be attended, especially when the medication is used at a late stage of the disease. Because pioglitazone is usually a second or third line antidiabetic agent, the users are always characterized by older age, longer diabetes duration, poorer glycemic control, and higher rates of complications and comorbidities. Biased estimates will also result if these differences are not appropriately addressed in the analyses. Current evidence neither concludes nor excludes a causal role of pioglitazone on bladder cancer. Clinical trials aiming at evaluating the risk of cancer associated with a medication is not ethical and may not be expected to provide an answer on the issue of pioglitazone-related bladder cancer. However, a meta-analysis using all available clinical trials to compare the bladder cancer risk between

  7. H-RAS, K-RAS, and N-RAS gene activation in human bladder cancers.

    Science.gov (United States)

    Przybojewska, B; Jagiello, A; Jalmuzna, P

    2000-08-01

    Bladder cancer is one of the leading causes of cancer death in most developed countries. In this work, 19 bladder cancer specimens, along with their infiltrations of the urinary bladder wall from the same patients, were examined for the presence of H-RAS, K-RAS, and N-RAS activation using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The H-RAS activation was found in 15 (about 84%) of the 19 bladder cancers studied. The same results were obtained in the infiltrating urinary bladder wall samples. N-RAS gene mutations were observed in all cases (except 1) in which H-RAS gene mutations were detected. The results suggest a strong relationship between H-RAS and N-RAS gene activation in bladder cancer. Changes in the K-RAS gene in bladder cancers seem to be a rare event; this is in agreement with findings of other authors. We found activation of the gene in one specimen of bladder cancer and its infiltration of the urinary bladder wall in the same patient.

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

    Science.gov (United States)

    Joshi, Bharat H; Leland, Pamela; Lababidi, Samir; Varrichio, Frederick; Puri, Raj K

    2014-12-01

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

  9. Expression and distribution of transient receptor potential (TRP) channels in bladder epithelium.

    Science.gov (United States)

    Yu, Weiqun; Hill, Warren G; Apodaca, Gerard; Zeidel, Mark L

    2011-01-01

    The urothelium is proposed to be a sensory tissue that responds to mechanical stress by undergoing dynamic membrane trafficking and neurotransmitter release; however, the molecular basis of this function is poorly understood. Transient receptor potential (TRP) channels are ideal candidates to fulfill such a role as they can sense changes in temperature, osmolarity, and mechanical stimuli, and several are reported to be expressed in the bladder epithelium. However, their complete expression profile is unknown and their cellular localization is largely undefined. We analyzed expression of all 33 TRP family members in mouse bladder and urothelium by RT-PCR and found 22 specifically expressed in the urothelium. Of the latter, 10 were chosen for closer investigation based on their known mechanosensory or membrane trafficking functions in other cell types. Western blots confirmed urothelial expression of TRPC1, TRPC4, TRPV1, TRPV2, TRPV4, TRPM4, TRPM7, TRPML1, and polycystins 1 and 2 (PKD1 and PKD2) proteins. We further defined the cellular and subcellular localization of all 10 TRP channels. TRPV2 and TRPM4 were prominently localized to the umbrella cell apical membrane, while TRPC4 and TRPV4 were identified on their abluminal surfaces. TRPC1, TRPM7, and TRPML1 were localized to the cytoplasm, while PKD1 and PKD2 were expressed on the apical and basolateral membranes of umbrella cells as well as in the cytoplasm. The cellular location of TRPV1 in the bladder has been debated, but colocalization with neuronal marker calcitonin gene-related peptide indicated clearly that it is present on afferent neurons that extend into the urothelium, but may not be expressed by the urothelium itself. These findings are consistent with the hypothesis that the urothelium acts as a sentinel and by expressing multiple TRP channels it is likely it can detect and presumably respond to a diversity of external stimuli and suggest that it plays an important role in urothelial signal

  10. Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells.

    Science.gov (United States)

    Lee, Hyun-Wook; Wang, Hsiang-Tsui; Weng, Mao-wen; Hu, Yu; Chen, Wei-sheng; Chou, David; Liu, Yan; Donin, Nicholas; Huang, William C; Lepor, Herbert; Wu, Xue-Ru; Wang, Hailin; Beland, Frederick A; Tang, Moon-shong

    2014-06-15

    Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants, can cause bladder tumor in rat models. Their role in TS related BC has not been forthcoming. To establish the relationship between acrolein and 4-ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT), and measured their mutagenicity in human urothelial cells. We found that the acrolein-dG levels in NHUM and BTT are 10-30 fold higher than 4-ABP-DNA adduct levels and that the acrolein-dG levels in BTT are 2 fold higher than in NHUM. Both acrolein-dG and 4-ABP-DNA adducts are mutagenic; however, the former are 5 fold more mutagenic than the latter. These two types of DNA adducts induce different mutational signatures and spectra. We found that acrolein inhibits nucleotide excision and base excision repair and induces repair protein degradation in urothelial cells. Since acrolein is abundant in TS, inhaled acrolein is excreted into urine and accumulates in the bladder and because acrolein inhibits DNA repair and acrolein-dG DNA adducts are mutagenic, we propose that acrolein is a major bladder carcinogen in TS.

  11. Bladder-like graphical representation of p53 gene alterations in some human cancers

    International Nuclear Information System (INIS)

    Helal, N.L.; Dorrah, M.; LI, C.

    2005-01-01

    the p53 tumor suppressor gene is mutated in about half of all human cancer cells. These mutations are not only important in tumor progression but apparently also in the response of some tumors to chemotherapy and radiation treatment, thus to clinical outcome. Recent studies have shown that cells carrying p53 mutations are more resistant to radiation and chemotherapy than cells with functional p53. More than 15000 tumors with Tp53 mutations were published, leadingto the description of more than 1500 different Tp53 mutants (at the site http:// p53. curie.fr). To exploit this huge bulk of data, specific analytic tools were highly warranted. Also, new computational techniques for rapid determination of such information and comparative studies of different mutations are required. In the present study, a mathematical method for the IARC library p53 mutation database comparing p53 mutations occurring in four different cancers was described. The sizes of the four cancers in the database were bladder (860), liver (786), brain (1170) and skin (38) cancers, for a total of 2854 of p53 mutations. The study was carried out on exons 4-8 of p53 for the four cancers under investigation. From this study, it can be quantitatively obtained some information for each characteristic sequence. The data showed that exon 8 was the most mutant exon in skin cancer and exon 7 was the lowest one. In hepatocellular carcinoma, exon 4 was the most mutant exon and exon 7 was the lowest mutant exon. Brain cancer showed high mutation in exon 8 and low mutation at exon 6. Finally, bladder mutation was mostly mutated at exon 6 comparing to the least value of exon 7. It is expected that this study of p53 mutation may provide useful information for the diagnosis, prognosis and treatment of cancer

  12. Identification of a novel human deoxynivalenol metabolite enhancing proliferation of intestinal and urinary bladder cells

    Science.gov (United States)

    Warth, Benedikt; Del Favero, Giorgia; Wiesenberger, Gerlinde; Puntscher, Hannes; Woelflingseder, Lydia; Fruhmann, Philipp; Sarkanj, Bojan; Krska, Rudolf; Schuhmacher, Rainer; Adam, Gerhard; Marko, Doris

    2016-09-01

    The mycotoxin deoxynivalenol (DON) is an abundant contaminant of cereal based food and a severe issue for global food safety. We report the discovery of DON-3-sulfate as a novel human metabolite and potential new biomarker of DON exposure. The conjugate was detectable in 70% of urine samples obtained from pregnant women in Croatia. For the measurement of urinary metabolites, a highly sensitive and selective LC-MS/MS method was developed and validated. The method was also used to investigate samples from a duplicate diet survey for studying the toxicokinetics of DON-3-sulfate. To get a preliminary insight into the biological relevance of the newly discovered DON-sulfates, in vitroexperiments were performed. In contrast to DON, sulfate conjugates lacked potency to suppress protein translation. However, surprisingly we found that DON-sulfates enhanced proliferation of human HT-29 colon carcinoma cells, primary human colon epithelial cells (HCEC-1CT) and, to some extent, also T24 bladder cancer cells. A proliferative stimulus, especially in tumorigenic cells raises concern on the potential impact of DON-sulfates on consumer health. Thus, a further characterization of their toxicological relevance should be of high priority.

  13. Concurrent Autophagy Inhibition Overcomes the Resistance of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Human Bladder Cancer Cells.

    Science.gov (United States)

    Kang, Minyong; Lee, Kyoung-Hwa; Lee, Hye Sun; Jeong, Chang Wook; Kwak, Cheol; Kim, Hyeon Hoe; Ku, Ja Hyeon

    2017-02-04

    Despite the potential therapeutic efficacy of epithelial growth factor receptor (EGFR) inhibitors in the treatment of advanced stage bladder cancer, there currently is no clear evidence to support this hypothesis. In this study, we investigate whether the concurrent treatment of autophagy-blocking agents with EGFR inhibitors exerts synergistic anti-cancer effects in T24 and J82 human bladder cancer cells. Lapatinib and gefitinib were used as EGFR inhibitors, and bafilomycin A1 (BFA1), chloroquine (CQ) and 3-methyladenine (3-MA) were used as the pharmacologic inhibitors of autophagy activities. To assess the proliferative and self-renewal capabilities, the Cell Counting Kit-8 (CCK-8) assay and a clonogenic assay were performed, respectively. To examine apoptotic cell death, flow cytometry using annexin-V/propidium iodide (PI) was used. To measure the autophagy activities, the expression levels of LC3I and II was determined by Western blot analysis. To validate the synergistic effects of autophagy inhibition with EGFR inhibitors, we specifically blocked key autophagy regulatory gene ATG12 by transfection of small interference RNA and examined the phenotypic changes. Of note, lapatinib and gefitinib triggered autophagy activities in T24 and J82 human bladder cancer cells, as indicated by upregulation of LC3II. More importantly, inhibiting autophagy activities with pharmacologic inhibitors (BFA1, CQ or 3-MA) remarkably reduced the cell viabilities and clonal proliferation of T24 and J82 cells, compared to those treated with either of the agents alone. We also obtained similar results of the enhanced anti-cancer effects of EGFR inhibitors by suppressing the expression of ATG12. Notably, the apoptotic assay showed that synergistic anti-cancer effects were induced via the increase of apoptotic cell death. In summary, concomitant inhibition of autophagy activities potentiated the anti-cancer effects of EGFR inhibitors in human bladder cancer cells, indicating a novel

  14. Concurrent Autophagy Inhibition Overcomes the Resistance of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Human Bladder Cancer Cells

    Directory of Open Access Journals (Sweden)

    Minyong Kang

    2017-02-01

    Full Text Available Despite the potential therapeutic efficacy of epithelial growth factor receptor (EGFR inhibitors in the treatment of advanced stage bladder cancer, there currently is no clear evidence to support this hypothesis. In this study, we investigate whether the concurrent treatment of autophagy-blocking agents with EGFR inhibitors exerts synergistic anti-cancer effects in T24 and J82 human bladder cancer cells. Lapatinib and gefitinib were used as EGFR inhibitors, and bafilomycin A1 (BFA1, chloroquine (CQ and 3-methyladenine (3-MA were used as the pharmacologic inhibitors of autophagy activities. To assess the proliferative and self-renewal capabilities, the Cell Counting Kit-8 (CCK-8 assay and a clonogenic assay were performed, respectively. To examine apoptotic cell death, flow cytometry using annexin-V/propidium iodide (PI was used. To measure the autophagy activities, the expression levels of LC3I and II was determined by Western blot analysis. To validate the synergistic effects of autophagy inhibition with EGFR inhibitors, we specifically blocked key autophagy regulatory gene ATG12 by transfection of small interference RNA and examined the phenotypic changes. Of note, lapatinib and gefitinib triggered autophagy activities in T24 and J82 human bladder cancer cells, as indicated by upregulation of LC3II. More importantly, inhibiting autophagy activities with pharmacologic inhibitors (BFA1, CQ or 3-MA remarkably reduced the cell viabilities and clonal proliferation of T24 and J82 cells, compared to those treated with either of the agents alone. We also obtained similar results of the enhanced anti-cancer effects of EGFR inhibitors by suppressing the expression of ATG12. Notably, the apoptotic assay showed that synergistic anti-cancer effects were induced via the increase of apoptotic cell death. In summary, concomitant inhibition of autophagy activities potentiated the anti-cancer effects of EGFR inhibitors in human bladder cancer cells, indicating

  15. 1,25D3 enhances antitumor activity of gemcitabine and cisplatin in human bladder cancer models

    Science.gov (United States)

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

    2010-01-01

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

  16. Cisplatin induces protective autophagy through activation of BECN1 in human bladder cancer cells

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    Lin JF

    2017-05-01

    Full Text Available Ji-Fan Lin,1 Yi-Chia Lin,2 Te-Fu Tsai,2,3 Hung-En Chen,2 Kuang-Yu Chou,2,3 Thomas I-Sheng Hwang2–4 1Central Laboratory, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, 2Division of Urology, School of Medicine, Fu-Jen Catholic University, New Taipei, 3Division of Urology, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, 4Department of Urology, Taipei Medical University, Taipei, Taiwan Purpose: Cisplatin-based chemotherapy is the first line treatment for several cancers including bladder cancer (BC. Autophagy induction has been implied to contribute to cisplatin resistance in ovarian cancer; and a high basal level of autophagy has been demonstrated in human bladder tumors. Therefore, it is reasonable to speculate that autophagy may account for the failure of cisplatin single treatment in BC. This study investigated whether cisplatin induces autophagy and the mechanism involved using human BC cell lines.Materials and methods: Human BC cells (5637 and T24 were used in this study. Cell viability was detected using water soluble tetrazolium-8 reagents. Autophagy induction was detected by monitoring the levels of light chain 3 (LC3-II and p62 by Western blot, LC3-positive puncta formation by immunofluorescence, and direct observation of the autophagolysosome (AL formation by transmission electron microscopy. Inhibitors including bafilomycin A1 (Baf A1, chloroquine (CQ, and shRNA-based lentivirus against autophagy-related genes (ATG7 and ATG12 were utilized. Apoptosis level was detected by caspase 3/7 activity and DNA fragmentation.Results: Cisplatin decreased cell viability and induced apoptosis of 5637 and T24 cells in a dose- and time-dependent manner. The increased LC3-II accumulation, p62 clearance, the number of LC3-positive puncta, and ALs in cisplatin-treated cells suggested that cisplatin indeed induces autophagy. Inhibition of cisplatin-induced autophagy using Baf A1, CQ, or ATG7/ATG12 shRNAs significantly enhanced cytotoxicity of

  17. Cisplatin induces protective autophagy through activation of BECN1 in human bladder cancer cells.

    Science.gov (United States)

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

    2017-01-01

    Cisplatin-based chemotherapy is the first line treatment for several cancers including bladder cancer (BC). Autophagy induction has been implied to contribute to cisplatin resistance in ovarian cancer; and a high basal level of autophagy has been demonstrated in human bladder tumors. Therefore, it is reasonable to speculate that autophagy may account for the failure of cisplatin single treatment in BC. This study investigated whether cisplatin induces autophagy and the mechanism involved using human BC cell lines. Human BC cells (5637 and T24) were used in this study. Cell viability was detected using water soluble tetrazolium-8 reagents. Autophagy induction was detected by monitoring the levels of light chain 3 (LC3)-II and p62 by Western blot, LC3-positive puncta formation by immunofluorescence, and direct observation of the autophagolysosome (AL) formation by transmission electron microscopy. Inhibitors including bafilomycin A1 (Baf A1), chloroquine (CQ), and shRNA-based lentivirus against autophagy-related genes (ATG7 and ATG12) were utilized. Apoptosis level was detected by caspase 3/7 activity and DNA fragmentation. Cisplatin decreased cell viability and induced apoptosis of 5637 and T24 cells in a dose-and time-dependent manner. The increased LC3-II accumulation, p62 clearance, the number of LC3-positive puncta, and ALs in cisplatin-treated cells suggested that cisplatin indeed induces autophagy. Inhibition of cisplatin-induced autophagy using Baf A1, CQ, or ATG7/ATG12 shRNAs significantly enhanced cytotoxicity of cisplatin toward BC cells. These results indicated that cisplatin induced protective autophagy which may contribute to the development of cisplatin resistance and resulted in treatment failure. Mechanistically, upregulation of beclin-1 (BECN1) was detected in cisplatin-treated cells, and knockdown of BECN1 using shRNA attenuated cisplatin-induced autophagy and subsequently enhanced cisplatin-induced apoptosis. Collectively, the study results

  18. Dual isotope scintiscan. New method for evaluating bladder function

    International Nuclear Information System (INIS)

    Lipshultz, L.I.; Corriere, J.N. Jr.

    1974-01-01

    Technetium-99m radioactive colloid particles were suspended in an iodine-131 Hippuran radioactive fluid medium and placed into the bladders of six patients. Two normal patients and one with only one urinary tract infection voided the fluid and particles synchronously, while three with recurrent urinary tract infections eliminated the particles at a much slower rate than the fluid. A change in either the physical contour or secretory activity of the bladder urothelium is postulated as the cause of particle retention in these patients with chronic infections

  19. Human β-defensin 2 may inhibit internalisation of bacillus Calmette-Guérin (BCG) in bladder cancer cells.

    Science.gov (United States)

    Kim, Jung Hoon; Kim, Soon-Ja; Lee, Kyung Mee; Chang, In Ho

    2013-10-01

    To investigate whether secretion of human β-defensin 2 (HBD-2) is induced by bacillus Calmette-Guérin (BCG) and to determine whether HBD-2 affects BCG internalisation in bladder cancer cells. Reverse transcription-polymerase chain reaction analysis was used to determine whether HBD-2 mRNA increases after incubation with BCG. HBD-2 proteins in 5637 and T24 human bladder cancer cell lines were assayed by enzyme-linked immunosorbent assay. The internalisation rate was evaluated by double immunofluorescence assay and confocal microscopy to test the optimal dose of HBD-2 for BCG internalisation. We also investigated the difference in internalisation rates and cell viability between recombinant HBD-2 protein, anti-HBD-2 antibody, and HBD-2 plus anti-HBD-2 antibody pretreatments. BCG induced HBD-2 mRNA expression and HBD-2 production dose and time-dependently in bladder cancer cells and affected BCG internalisation. Pretreatment with recombinant HBD-2 protein lowered internalisation of BCG dose-dependently. Moreover, anti-HBD-2 antibody prevented the effect of HBD-2 on BCG internalisation in bladder cancer cells. The internalisation rate of BCG pretreated with anti-HBD-2 antibody was higher than that in the control in 5637 (P internalisation rate in cells pretreated with anti-HBD-2 antibody plus recombinant HBD-2 protein was higher than that in the control in 5637 (P internalisation, which plays an important role during the initiation and propagation of the immunotherapeutic response in bladder cancer cells. © 2013 The Authors. BJU International © 2013 BJU International.

  20. Transcriptional Modulation of the ERK1/2 MAPK and NF-kB pathways in Human Urothelial cells after trivalent arsenical exposure: Implications for urinary bladder cancer

    Science.gov (United States)

    Chronic exposure to drinking water contaminated with inorganic arsenic (iAs) is associated with an increased risk ofurinary bladder (DB) cancers in humans. Rodent models administered particular arsenicals have indicated urothelial necrosis followed by regenerative proliferation i...

  1. [Bladder pain syndrome--an urological-gynecological problem].

    Science.gov (United States)

    Zabkowski, Tomasz; Bortnowski, Leszek; Zieliński, Henryk

    2011-03-01

    Bladder Pain Syndrome remains a great challenge for urologists, both in diagnostics and treatment. Etiopathogenesis of the disease is unknown. It is reported that the reason for Bladder Pain Syndrome is the urothelium dysfunction resulting in the destruction of the protective glycosaminoglycan layer/barrier protecting the urothelium from bacteria adhesion and penetration of toxic substances/by bacteria. It is considered to be a syndrome of dysuria and diuresis. Urine analysis usually is normal. It is diagnosed after exclusion of other causes leading to painful symptoms. It is estimated that 90% of the cases of the disease concern women. Treatment with glycocorticosteroids, antihistaminic drugs and antiallergic drugs was not successful. The attempts to find the right method of treatment led to the introduction of hyaluronic acid, which alleviated Bladder Pain Syndrome and its symptoms. Hyaluronic acid reacting with glycosaminoglycans on the bladder decreases penetrability of irritant substances. The patients were treated with 4-8 weekly instillations--40 mg of hyaluronic acid in 50 ml NaCl solution for 1-2 months. After the last instillation, therapy is repeated for the next 6-8 months with one instillation monthly. This method is for patients a chance for getting rid of painful symptoms from the bladder

  2. Receptors involved in the modulation of guinea pig urinary bladder motility by prostaglandin D2

    Science.gov (United States)

    Guan, Na N; Svennersten, Karl; de Verdier, Petra J; Wiklund, N Peter; Gustafsson, Lars E

    2015-01-01

    Background and Purpose We have described a urothelium-dependent release of PGD2-like activity which had inhibitory effects on the motility of guinea pig urinary bladder. Here, we have pharmacologically characterized the receptors involved and localized the sites of PGD2 formation and of its receptors. Experimental Approach In the presence of selective DP and TP receptor antagonists alone or combined, PGD2 was applied to urothelium-denuded diclofenac-treated urinary bladder strips mounted in organ baths. Antibodies against PGD2 synthase and DP1 receptors were used with Western blots and for histochemistry. Key Results PGD2 inhibited nerve stimulation -induced contractions in strips of guinea pig urinary bladder with estimated pIC50 of 7.55 ± 0.15 (n = 13), an effect blocked by the DP1 receptor antagonist BW-A868C. After blockade of DP1 receptors, PGD2 enhanced the contractions, an effect abolished by the TP receptor antagonist SQ-29548. Histochemistry revealed strong immunoreactivity for PGD synthase in the urothelium/suburothelium with strongest reaction in the suburothelium. Immunoreactive DP1 receptors were found in the smooth muscle of the bladder wall with a dominant localization to smooth muscle membranes. Conclusions and Implications In guinea pig urinary bladder, the main effect of PGD2 is an inhibitory action via DP1 receptors localized to the smooth muscle, but an excitatory effect via TP receptors can also be evoked. The urothelium with its suburothelium might signal to the smooth muscle which is rich in PGD2 receptors of the DP1 type. The results are important for our understanding of regulation of bladder motility. PMID:25917171

  3. Sensory dysfunction of bladder mucosa and bladder oversensitivity in a rat model of metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Wei-Chia Lee

    Full Text Available PURPOSE: To study the role of sensory dysfunction of bladder mucosa in bladder oversensitivity of rats with metabolic syndrome. MATERIALS AND METHODS: Female Wistar rats were fed a fructose-rich diet (60% or a normal diet for 3 months. Based on cystometry, the fructose-fed rats (FFRs were divided into a group with normal detrusor function or detrusor overactivity (DO. Acidic adenosine triphosphate (ATP solution (5mM, pH 3.3 was used to elicit reflex micturition. Cystometric parameters were evaluated before and after drug administration. Functional proteins of the bladder mucosa were assessed by western blotting. RESULTS: Compared to the controls, intravesical acidic ATP solution instillation induced a significant increase in provoked phasic contractions in both FFR groups and a significant decrease in the mean functional bladder capacity of group DO. Pretreatment with capsaicin for C-fiber desentization, intravesical liposome for mucosal protection, or intravenous pyridoxal 5-phosphate 6-azophenyl-2',4'-disulfonic acid for antagonized purinergic receptors can interfere with the urodynamic effects of intravesical ATP in FFRs and controls. Over-expression of TRPV1, P2X(3, and iNOS proteins, and down-regulation of eNOS proteins were observed in the bladder mucosa of both fructose-fed groups. CONCLUSIONS: Alterations of sensory receptors and enzymes in the bladder mucosa, including over-expression of TRPV1, P2X(3, and iNOS proteins, can precipitate the emergence of bladder phasic contractions and oversensitivity through the activation of C-afferents during acidic ATP solution stimulation in FFRs. The down-regulation of eNOS protein in the bladder mucosa of FFRs may lead to a failure to suppress bladder oversensitivity and phasic contractions. Sensory dysfunction of bladder mucosa and DO causing by metabolic syndrome are easier to elicit bladder oversensitivity to certain urothelium stimuli.

  4. Human papilloma virus DNA and p53 mutation analysis on bladder washes in relation to clinical outcome of bladder cancer.

    NARCIS (Netherlands)

    Moonen, P.M.J.; Bakkers, J.M.J.E.; Kiemeney, L.A.L.M.; Schalken, J.A.; Melchers, W.J.G.; Witjes, J.A.

    2007-01-01

    OBJECTIVES: High-risk human papilloma virus (HPV) types stimulate degradation and deactivation of protein associated with the p53 tumour suppressor gene via the ubiquitin-dependent pathway. For a long time, changes of the p53 tumour suppressor gene have been correlated with poor clinical outcome in

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

    Science.gov (United States)

    Kang, Minyong; Jeong, Chang Wook; Ku, Ja Hyeon; Kwak, Cheol; Kim, Hyeon Hoe

    2014-01-01

    Statins are cholesterol reduction agents that exhibit anti-cancer activity in several human cancers. Because autophagy is a crucial survival mechanism for cancer cells under stress conditions, cooperative inhibition of autophagy acts synergistically with other anti-cancer drugs. Thus, this study investigates whether combined treatment of atorvastatin and autophagy inhibitors results in enhancing the cytotoxic effects of atorvastatin, upon human bladder cancer cells, T24 and J82, in vitro. To measure cell viability, we performed the EZ-Cytox cell viability assay. We examined apoptosis by flow cytometry using annexin-V/propidium iodide (PI and western blot using procaspase-3 and poly (ADP-ribose) polymerase (PARP) antibodies. To examine autophagy activation, we evaluated the co-localization of LC3 and LysoTracker by immunocytochemistry, as well as the expression of LC3 and p62/sequestosome-1 (SQSTM1) by western blot. In addition, we assessed the survival and proliferation of T24 and J82 cells by a clonogenic assay. We found that atorvastatin reduced the cell viability of T24 and J82 cells via apoptotic cell death and induced autophagy activation, shown by the co-localization of LC3 and LysoTracker. Moreover, pharmacologic inhibition of autophagy significantly enhanced atorvastatin-induced apoptosis in T24 and J82 cells. In sum, inhibition of autophagy potentiates atorvastatin-induced apoptotic cell death in human bladder cancer cells in vitro, providing a potential therapeutic approach to treat bladder cancer. PMID:24815071

  6. Cheliensisin A (Chel A) induces apoptosis in human bladder cancer cells by promoting PHLPP2 protein degradation.

    Science.gov (United States)

    Zhang, Ruowen; Che, Xun; Zhang, Jingjie; Li, Yang; Li, Jingxia; Deng, Xu; Zhu, Junlan; Jin, Honglei; Zhao, Qinshi; Huang, Chuanshu

    2016-10-11

    Cheliensisin A (Chel A), a styryl-lactone compound extracted from Goniothalamus cheliensis, is reported to have significant anti-cancer effects in various cancer cells. Here we demonstrated that Chel A treatment resulted in apoptosis and an inhibition of anchorage-independent growth in human bladder cancer T24, T24T and U5637 cells. Mechanistic studies showed that such effect is mediated by PH domain and Leucine rich repeat Protein Phosphatases (PHLPP2) protein. Chel A treatment led to PHLPP2 degradation and subsequently increased in c-Jun phosphorylation. Moreover PHLPP2 degradation could be attenuated by inhibition of autophagy, which was mediated by Beclin 1. Collectively, we discover that Chel A treatment induces Beclin-dependent autophagy, consequently mediates PHLPP2 degradation and JNK/C-Jun phosphorylation and activation, further in turn contributing to apoptosis in human bladder cancer cells. Current studies provide a significant insight into understanding of anticancer effect of Chel A in treatment of human bladder cancer.

  7. Lectin immunohistochemical evaluation of human bladder carcinomas. A comparison of Carnoy's and formalin fixation.

    Science.gov (United States)

    Okamura, T; Ueda, K; Ohtaguro, K; Inoue, K; Washida, H; Mori, M; Tatemoto, Y; Fukushima, S

    1993-10-01

    A lectin immunohistochemical analysis of 51 human bladder carcinomas, including 44 cases of transitional cell carcinoma (TCC) (G1, 15 cases; G2, 17 cases; G3, 12 cases) and 7 cases of squamous cell carcinoma (SCC), was performed. Tissues were obtained by cold punch biopsies, fixed in Carnoy's or 10% formalin solution, stained for binding of 10 different lectins, and evaluated under the light microscope. The lectins used were concanavalin agglutinin (Con A), soybean agglutinin (SBA), Lotus tetragonolobus agglutinin (LTA), Dolichos biflorusa agglutinin (DBA), peanut agglutinin (PNA), Ricinus communis agglutinin I (RCA1), Ulex europaeus agglutinin I, II (UEA-I, II), wheat germ agglutinin (WGA), and Pisum sativum agglutinin (PEA). TCC prepared with Carnoy's fixation tended to show moderately positive Con A, UEA-I, and WGA reactions for G1, and strongly positive reactions for G2 and G3 lesions. UEA-II was mainly negative in G1, but tended to increase to become moderate in G3. DBA tended to show a moderately positive reaction in G1 and G2, but was mainly negative in G3. With formalin fixation, only RCA1 demonstrated grade specific variation, tendency to react moderately in the G1 and G2 cases, and strongly in G3. There were no further differences among the histopathological grades of TCC for other lectins. Thus, Carnoy's fixation appears superior for distinguishing between grades of lesions. SCC tended to react more strongly than TCC with all the various lectins except PEA, independent of fixation.

  8. [Continuous registration of the filling volume of the human urinary bladder].

    Science.gov (United States)

    Preussner, P R

    1991-11-01

    A sensing system for continuous recording of bladder volume is described. The system is intended for use in particular in patients with paraplegia or bladder plastique. Owing to the very simple measuring procedure employed the implantable components can be designed for very low power consumption. Also, there is no need for an additional data transfer from inside the body to the exterior, because measurement and telemetry are physically the same procedures.

  9. Differences of response of human bladder cancer cells to photodynamic therapy (PDT) with Hypericum perforantum L extract and Photofrin

    Science.gov (United States)

    Nseyo, Unyime; Kim, Albert; Stavropoulos, Nikos E.; Skalkos, Dimitris; Nseyo, Unwana U.; Chung, Theodore D.

    2005-04-01

    Refractory carcinoma in situ and resistant multifocal transitional cell carcinoma (TCC) of the human urinary bladder respond modestly to PHOTOFRIN (PII) PDT. Hypericum perforatum L., (St. John"s wort /Epirus" Vasalmo, Greece), a medicinal plant used for many human ailments, is under investigation as a new photosensitizer. We have reported on the antiproliferative activity of the lipophilic extract of the Hypericum perforatum L. (HP) against cultured T-24, and NBT-11 bladder cancer cells. We investigated response of the polar methanolic fraction (PMF) of the HP extract versus PHOTOFRIN in photodynamic therapy (PDT) of human bladder cancer cells, RT-4 and T-24.The PMF was extracted from the dry herb with methanol, followed by liquid extraction with petroleum ether. RT-4/T-24, were plated (105 cells/well) and placed in the incubator (370 C, 5%CO) for 24 hours prior to addition of drugs. PII 2ug/ml, or PMF 60ug /ml was added and incubation continued. After 24 hours, the cells were treated with laser light (630nm) with 0,1,2,4 and 8 Joules. The cells were then washed and reincubated for another 24 hours. After this incubation cell survival was assessed by the MTT assay. PMF-PDT induced percent cell kill of 0%, 0%, 0%, 29% and 75%, in RT-4 cells (primary noninvasive urinary bladder TCC) versus 5%, 9%, 13%, 69% and 86%, in T-24 cells(metastatic TTC) at 0,1,2,4 and 8 Joules respectively. PII-PDT induced cell kill of 0 %, 0% ,0%,0% and 9 %, in RT-4 cells versus 0%,10%,0%,21% and 77%, in T-24 cells at 0,1,2,4 and 8 Joules respectively.RT-24 cells were relatively more resistant than T-24 cells to PMF and PII-PDT. Understanding mechanisms of such differential responses might prove useful

  10. [Myofibroblasts and afferent signalling in the urinary bladder. A concept].

    Science.gov (United States)

    Neuhaus, J; Scholler, U; Freick, K; Schwalenberg, T; Heinrich, M; Horn, L C; Stolzenburg, J U

    2008-09-01

    Afferent signal transduction in the urinary bladder is still not clearly understood. An increasing body of evidence supports the view of complex interactions between urothelium, suburothelial myofibroblasts, and sensory nerves. Bladder tissue from tumour patients was used in this study. Methods included confocal immunofluorescence, polymerase chain reaction, calcium imaging, and fluorescence recovery after photobleaching (FRAP).Myofibroblasts express muscarinic and purinergic receptors. They show constitutive spontaneous activity in calcium imaging, which completely depends on extracellular calcium. Stimulation with carbachol and ATP-evoked intracellular calcium transients also depend on extracellular calcium. The intensive coupling between the cells is significantly diminished by incubation with TGF-beta 1. Myofibroblasts form an important cellular element within the afferent signalling of the urinary bladder. They possess all features required to take part in the complex interactions with urothelial cells and sensory nerves. Modulation of their function by cytokines may provide a pathomechanism for bladder dysfunction.

  11. Prostaglandin D2 effects and DP1 /DP2 receptor distribution in guinea pig urinary bladder out-flow region.

    Science.gov (United States)

    Guan, Na N; Svennersten, Karl; de Verdier, Petra J; Wiklund, N Peter; Gustafsson, Lars E

    2017-02-01

    The proximal urethra and urinary bladder trigone play important roles in continence. We have previously shown that PGD 2 is released from guinea pig bladder urothelium/suburothelium and can inhibit detrusor contractile responses. We presently wished to investigate PGD 2 actions in guinea pig out-flow region and the distribution of DP 1 /DP 2 receptors. The effects of PGD 2 on urothelium-intact trigone and proximal urethra contractility were studied in organ bath experiments. Expression of DP 1 /DP 2 receptor proteins was analysed by western blot. Immunohistochemistry was used to identify distribution of DP 1 /DP 2 receptors. PGD 2 in a dose-dependent manner inhibited trigone contractions induced by electrical field stimulation (EFS) and inhibited spontaneous contractions of the proximal urethra. PGD 2 was equally (trigone) or slightly less potent (urethra) compared with PGE 2 . Expression of DP 1 and DP 2 receptors was found in male guinea pig bladder trigone, neck and proximal urethra. In the trigone and proximal urethra, DP 1 receptors were found on the membrane of smooth muscle cells and weak immunoreactivty was observed in the urothelium. DP 2 receptors were distributed more widespread, weakly and evenly in the urothelium and smooth muscles. Inhibitory effects by PGD 2 on motor activity of guinea pig trigone and proximal urethra are consistent with finding DP 1 and DP 2 receptors located in the urothelium and smooth muscle cells of the trigone and proximal urethra, and PGD 2 may therefore be a modulator of the bladder out-flow region, possibly having a function in regulation of micturition and a role in overactive bladder syndrome. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  12. Nrf2 protects human bladder urothelial cells from arsenite and monomethylarsonous acid toxicity

    International Nuclear Information System (INIS)

    Wang Xiaojun; Sun Zheng; Chen Weimin; Eblin, Kylee E.; Gandolfi, Jay A.; Zhang, Donna D.

    2007-01-01

    Arsenic is widely spread in our living environment and imposes a big challenge on human health worldwide. Arsenic damages biological systems through multiple mechanisms including the generation of reactive oxygen species. The transcription factor Nrf2 regulates the cellular antioxidant response that protects cells from various insults. In this study, the protective role of Nrf2 in arsenic toxicity was investigated in a human bladder urothelial cell line, UROtsa. Using a UROtsa cell line stably infected with Nrf2-siRNA, we clearly demonstrate that compromised Nrf2 expression sensitized the cells to As(III)- and MMA(III)-induced toxicity. On the other hand, the activation of the Nrf2 pathway by tert-butylhydroquinone (tBHQ) and sulforaphane (SF), the known Nrf2-inducers, rendered UROtsa cells more resistant to As(III) and MMA(III). Furthermore, the wild-type mouse embryo fibroblast (WT-MEF) cells were protected from As(III)- and MMA(III)-induced toxicity following Nrf2 activation by tBHQ or SF, whereas neither tBHQ nor SF conferred protection in the Nrf2 -/- MEF cells, demonstrating that tBHQ- or SF-mediated protection against As(III)- and MMA(III)-induced toxicity depends on Nrf2 activation. These results, obtained by both loss of function and gain of function analyses, clearly demonstrate the protective role of Nrf2 in arsenic-induced toxicity. The current work lays the groundwork for using Nrf2 activators for therapeutic and dietary interventions against adverse effects of arsenic

  13. 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.

  14. Etiological role of human papillomavirus infection for inverted papilloma of the bladder.

    Science.gov (United States)

    Shigehara, Kazuyoshi; Sasagawa, Toshiyuki; Doorbar, John; Kawaguchi, Shohei; Kobori, Yoshitomo; Nakashima, Takao; Shimamura, Masayoshi; Maeda, Yuji; Miyagi, Tohru; Kitagawa, Yasuhide; Kadono, Yoshifumi; Konaka, Hiroyuki; Mizokami, Atsushi; Koh, Eitetsu; Namiki, Mikio

    2011-02-01

    The status of human papillomavirus (HPV) infection in urothelial inverted papilloma was examined in the present study. Formalin-fixed and paraffin-embedded tissues from eight cases of inverted papilloma of the bladder were studied. The presence of HPV-DNA was examined by modified GP5/6+PCR using archival tissue sections by microdissection. HPV genotype was determined with a Hybri-Max HPV genotyping kit. Immunohistochemical analysis for p16-INK4a, mcm7, HPV-E4, and L1, and in situ hybridization for the HPV genome were performed. HPV was detected in seven of eight cases (87.5%) of inverted papilloma. Three cases were diagnosed as inverted papilloma with atypia, while the remaining five were typical cases. HPV-18 was detected in two cases, including one inverted papilloma with atypia, and HPV-16 was detected in four cases, including one inverted papilloma with atypia. Multiple HPV type infection was detected in one typical case and one atypical case. High-risk HPV was present in all HPV-positive cases. Cellular proteins, p16-INK4a and mcm7, which are surrogate markers for HPV-E7 expression, were detected in all HPV-positive cases, and their levels were higher in inverted papilloma with atypia than in typical cases. In contrast, HPV-E4 and L1, which are markers for HPV propagation, were observed in some parts of the typical inverted papilloma tissue. High-risk HPV infection may be one of the causes of urothelial inverted papilloma, and inverted papilloma with atypia may have malignant potential. 2010 Wiley-Liss, Inc.

  15. [Structure and function of suburothelial myofibroblasts in the human urinary bladder under normal and pathological conditions].

    Science.gov (United States)

    Neuhaus, J; Heinrich, M; Schlichting, N; Oberbach, A; Fitzl, G; Schwalenberg, T; Horn, L-C; Stolzenburg, J-U

    2007-09-01

    Myofibroblasts play a pivotal role in numerous pathological alterations. Clarification of the structure and function and of the cellular plasticity of this cell type in the bladder may lead to new insights into the pathogenesis of lower urinary tract disorders. Bladder biopsies from patients with bladder carcinoma and interstitial cystitis were used to analyse the morphology and receptor expression using confocal immunofluorescence and electron microscopy. Cytokine effects and coupling behavior were tested in cultured myofibroblasts and detrusor smooth muscle cells. Myofibroblasts are in close contact with the suburothelial capillary network. They express Cx43 and form functional syncytia. The expression of muscarinic and purinergic receptors is highly variable. Dye coupling experiments showed differences to detrusor myocytes. Upregulation of smooth muscle cell alpha-actin and/or transdifferentiation into smooth muscle cells may contribute to the etiology of urge incontinence. A multi-step model is presented as a working hypothesis.

  16. 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.

  17. [New insights in the differential diagnosis of bladder pain syndrome].

    Science.gov (United States)

    Schwalenberg, T; Neuhaus, J; Horn, L-C; Alexander, H; Zimmermann, G; Ho Thi, P; Mallock, T; Stolzenburg, J-U

    2010-03-01

    The diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is challenging, since pathogenetic mechanisms and the definition of clinical relevant parameters are still under lively discussion. The criteria recently proposed by the European Society for the Study of Interstitial Cystitis (ESSIC) define a collective of patients based on the cardinal symptom of bladder pain which is heterogeneous, and therefore cannot receive standardised consistent therapy. Thus an extended diagnosis based on molecular markers seems to be indicated to render individual pharmacotherapy possible, and to contribute to elucidation of BPS/IC pathogenesis. For this purpose we feel the vital need for taking a bladder biopsy. The diagnosis of BPS/IC should rely on 3 "columns": (1) clinical diagnostics; (2) histopathology; (3) molecular diagnostics/protein expression. Since a significant contribution of the 3 functional units of the bladder to the pathophysiology is most evident, the examinations should ideally include urothelium, lamina propria, and detrusor musculature. Generation of receptor profiles of the detrusor muscle represents a first attempt to define a diagnostic tool for the individualisation of BPS/IC pharmacotherapy. Other factors, e.g., beta-hCG expression in the urothelium, need further evaluation. Extended BPS/IC diagnostics could be realistically integrated into routine patient care within a clinic/laboratory network. Georg Thieme Verlag Stuttgart New York.

  18. Hydrostatic pressure and muscarinic receptors are involved in the release of inflammatory cytokines in human bladder smooth muscle cells.

    Science.gov (United States)

    Liang, Zhou; Xin, Wei; Qiang, Liu; Xiang, Cai; Bang-Hua, Liao; Jin, Yang; De-Yi, Luo; Hong, Li; Kun-Jie, Wang

    2017-06-01

    Abnormal intravesical pressure results in a series of pathological changes. We investigated the effects of hydrostatic pressure and muscarinic receptors on the release of inflammatory cytokines in rat and human bladder smooth muscle cells (HBSMCs). Animal model of bladder outlet obstruction was induced by urethra ligation. HBSMCs were subjected to elevated hydrostatic pressure and/or acetylcholine (Ach). Macrophage infiltration in the bladder wall was determined by immunohistochemical staining. The expression of inflammatory genes was measured by RT-PCR, ELISA and immunofluorescence. In obstructed bladder, inflammatory genes and macrophage infiltration were remarkably induced. When HBSMCs were subjected to 200-300 cm H 2 O pressure for 2-24 h in vitro, the expressions of IL-6 and RANTES were significantly increased. Hydrostatic pressure promoted the protein levels of phospho-NFκB p65 and phospho-ERK1/2 as well as muscarinic receptors. Moreover, NFκB or ERK1/2 inhibitors suppressed pressure-induced inflammatory genes mRNA. When cells were treated with 1 μM acetylcholine for 6 h, a significant increase in IL-6 mRNA expression was detected. Acetylcholine also enhanced pressure-induced phospho-NFκB p65 and IL-6 protein expression. Additionally, pressure-induced IL-6 was partially suppressed by muscarinic receptors antagonists. Hydrostatic pressure and muscarinic receptors were involved in the secretion of inflammatory cytokines in HBSMCs, indicating a pro-inflammatory effect of the two factors in the pathological process of BOO. © 2016 Wiley Periodicals, Inc.

  19. Arsenite and monomethylarsonous acid generate oxidative stress response in human bladder cell culture

    International Nuclear Information System (INIS)

    Eblin, K.E.; Bowen, M.E.; Cromey, D.W.; Bredfeldt, T.G.; Mash, E.A.; Lau, S.S.; Gandolfi, A.J.

    2006-01-01

    Arsenicals have commonly been seen to induce reactive oxygen species (ROS) which can lead to DNA damage and oxidative stress. At low levels, arsenicals still induce the formation of ROS, leading to DNA damage and protein alterations. UROtsa cells, an immortalized human urothelial cell line, were used to study the effects of arsenicals on the human bladder, a site of arsenical bioconcentration and carcinogenesis. Biotransformation of As(III) by UROtsa cells has been shown to produce methylated species, namely monomethylarsonous acid [MMA(III)], which has been shown to be 20 times more cytotoxic. Confocal fluorescence images of UROtsa cells treated with arsenicals and the ROS sensing probe, DCFDA, showed an increase of intracellular ROS within five min after 1 μM and 10 μM As(III) treatments. In contrast, 50 and 500 nM MMA(III) required pretreatment for 30 min before inducing ROS. The increase in ROS was ameliorated by preincubation with either SOD or catalase. An interesting aspect of these ROS detection studies is the noticeable difference between concentrations of As(III) and MMA(III) used, further supporting the increased cytotoxicity of MMA(III), as well as the increased amount of time required for MMA(III) to cause oxidative stress. These arsenical-induced ROS produced oxidative DNA damage as evidenced by an increase in 8-hydroxyl-2'-deoxyguanosine (8-oxo-dG) with either 50 nM or 5 μM MMA(III) exposure. These findings provide support that MMA(III) cause a genotoxic response upon generation of ROS. Both As(III) and MMA(III) were also able to induce Hsp70 and MT protein levels above control, showing that the cells recognize the ROS and respond. As(III) rapidly induces the formation of ROS, possibly through it oxidation to As(V) and further metabolism to MMA(III)/(V). These studies provide evidence for a different mechanism of MMA(III) toxicity, one that MMA(III) first interacts with cellular components before an ROS response is generated, taking longer to

  20. Development of an Implantable Pudendal Nerve Stimulator To Restore Bladder Function in Humans After SCI

    Science.gov (United States)

    2016-10-01

    inhibited micturition reflex contraction during a slow infusion of the bladder (Figure Figure 5. Experimental Setup Page 7 of 17 6). This result...University of Pittsburgh (Pitt) and the InCube Labs have worked diligently during the first year of the contract and have managed to successfully accomplish

  1. Nano-BCG: A Promising Delivery System for Treatment of Human Bladder Cancer.

    Science.gov (United States)

    Buss, Julieti Huch; Begnini, Karine Rech; Bender, Camila Bonemann; Pohlmann, Adriana R; Guterres, Silvia S; Collares, Tiago; Seixas, Fabiana Kömmling

    2017-01-01

    Mycobacterium bovis bacillus Calmette-Guerin (BCG) remains at the forefront of immunotherapy for treating bladder cancer patients. However, the incidence of recurrence and progression to invasive cancer is commonly observed. There are no established effective intravesical therapies available for patients, whose tumors recur following BCG treatment, representing an important unmet clinical need. In addition, there are very limited options for patients who do not respond to or tolerate chemotherapy due to toxicities, resulting in poor overall treatment outcomes. Within this context, nanotechnology is an emergent and promising tool for: (1) controlling drug release for extended time frames, (2) combination therapies due to the ability to encapsulate multiple drugs simultaneously, (3) reducing systemic side effects, (4) increasing bioavailability, (5) and increasing the viability of various routes of administration. Moreover, bladder cancer is often characterized by high mutation rates and over expression of tumor antigens on the tumor cell surface. Therapeutic targeting of these biomolecules may be improved by nanotechnology strategies. In this mini-review, we discuss how nanotechnology can help overcome current obstacles in bladder cancer treatment, and how nanotechnology can facilitate combination chemotherapeutic and BCG immunotherapies for the treatment of non-muscle invasive urothelial bladder cancer.

  2. Nano-BCG: A Promising Delivery System for Treatment of Human Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Julieti Huch Buss

    2018-01-01

    Full Text Available Mycobacterium bovis bacillus Calmette–Guerin (BCG remains at the forefront of immunotherapy for treating bladder cancer patients. However, the incidence of recurrence and progression to invasive cancer is commonly observed. There are no established effective intravesical therapies available for patients, whose tumors recur following BCG treatment, representing an important unmet clinical need. In addition, there are very limited options for patients who do not respond to or tolerate chemotherapy due to toxicities, resulting in poor overall treatment outcomes. Within this context, nanotechnology is an emergent and promising tool for: (1 controlling drug release for extended time frames, (2 combination therapies due to the ability to encapsulate multiple drugs simultaneously, (3 reducing systemic side effects, (4 increasing bioavailability, (5 and increasing the viability of various routes of administration. Moreover, bladder cancer is often characterized by high mutation rates and over expression of tumor antigens on the tumor cell surface. Therapeutic targeting of these biomolecules may be improved by nanotechnology strategies. In this mini-review, we discuss how nanotechnology can help overcome current obstacles in bladder cancer treatment, and how nanotechnology can facilitate combination chemotherapeutic and BCG immunotherapies for the treatment of non-muscle invasive urothelial bladder cancer.

  3. Comparing Image Perception of Bladder Tumors in Four Different Storz Professional Image Enhancement System Modalities Using the íSPIES App

    NARCIS (Netherlands)

    Kamphuis, Guido M.; de Bruin, D. Martijn; Brandt, Martin J.; Knoll, Thomas; Conort, Pierre; Lapini, Alberto; Dominguez-Escrig, Jose L.; de La Rosette, Jean J. M. C. H.

    2016-01-01

    To evaluate the variation of interpretation of the same bladder urothelium image in different Storz Professional Image Enhancement System (SPIES) modalities. SPIES contains a White light (WL), Spectra A (SA), Spectra B (SB), and Clara and Chroma combined (CC) modality. An App for the iPAD retina was

  4. TRPV2 activation induces apoptotic cell death in human T24 bladder cancer cells: a potential therapeutic target for bladder cancer.

    Science.gov (United States)

    Yamada, Takahiro; Ueda, Takashi; Shibata, Yasuhiro; Ikegami, Yosuke; Saito, Masaki; Ishida, Yusuke; Ugawa, Shinya; Kohri, Kenjiro; Shimada, Shoichi

    2010-08-01

    To investigate the functional expression of the transient receptor potential vanilloid 2 (TRPV2) channel protein in human urothelial carcinoma (UC) cells and to determine whether calcium influx into UC cells through TRPV2 is involved in apoptotic cell death. The expression of TRPV2 mRNA in bladder cancer cell lines (T24, a poorly differentiated UC cell line and RT4, a well-differentiated UC cell line) was analyzed using reverse transcriptase-polymerase chain reaction. The calcium permeability of TRPV2 channels in T24 cells was investigated using a calcium imaging assay that used cannabidiol (CBD), a relatively selective TRPV2 agonist, and ruthenium red (RuR), a nonselective TRPV channel antagonist. The death of T24 or RT4 cells in the presence of CBD was evaluated using a cellular viability assay. Apoptosis of T24 cells caused by CBD was confirmed using an annexin-V assay and small interfering RNA (siRNA) silencing of TRPV2. TRPV2 mRNA was abundantly expressed in T24 cells. The expression level in UC cells was correlated with high-grade disease. The administration of CBD increased intracellular calcium concentrations in T24 cells. In addition, the viability of T24 cells progressively decreased with increasing concentrations of CBD, whereas RT4 cells were mostly unaffected. Cell death occurred via apoptosis caused by continuous influx of calcium through TRPV2. TRPV2 channels in UC cells are calcium-permeable and the regulation of calcium influx through these channels leads directly to the death of UC cells. TRPV2 channels in UC cells may be a potential new therapeutic target, especially in higher-grade UC cells. Copyright 2010 Elsevier Inc. All rights reserved.

  5. Expression and proliferation profiles of PKC, JNK and p38MAPK in physiologically stretched human bladder smooth muscle cells

    International Nuclear Information System (INIS)

    Wazir, Romel; Luo, De-Yi; Dai, Yi; Yue, Xuan; Tian, Ye; Wang, Kun-Jie

    2013-01-01

    Highlights: •Stretch induces proliferation in human bladder smooth muscle cells (HBSMC). •5% Equibiaxial elongation produces maximum proliferation. •Physiologic stretch decreases apoptotic cell death. •PKC is involved in functional modulation of bladder. •JNK and p38 are not involved in proliferating HBSMC. -- Abstract: Objective: To determine protein kinase C (PKC), c-Jun NH2-Terminal Kinase (JNK) and P38 mitogen-activated protein kinases (p38MAPK) expression levels and effects of their respective inhibitors on proliferation of human bladder smooth muscle cells (HBSMCs) when physiologically stretched in vitro. Materials and methods: HBSMCs were grown on silicone membrane and stretch was applied under varying conditions; (equibiaxial elongation: 2.5%, 5%, 10%, 15%, 20%, 25%), (frequency: 0.05, 0.1, 0.2, 0.5, 1 Hz). Optimal physiological stretch was established by assessing proliferation with 5-Bromo-2-deoxyuridine (BrdU) assay and flow cytometry. PKC, JNK and p38 expression levels were analyzed by Western blot. Specificity was maintained by employing specific inhibitors; (GF109203X for PKC, SP600125 for JNK and SB203580 for p38MAPK), in some experiments. Results: Optimum proliferation was observed at 5% equibiaxial stretch (BrdU: 0.837 ± 0.026 (control) to 1.462 ± 0.023)%, (P 0.05 SP600125) and (1.461 ± 0.01, P > 0.05 SB203580). These findings show that mechanical stretch can promote magnitude-dependent proliferative modulation through PKC and possibly JNK but not via p38MAPK in hBSMCs

  6. 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.

  7. Bladder Leiomyoma.

    Science.gov (United States)

    Caliskan, Selahattin; Sungur, Mustafa

    2017-03-01

    Leiomyoma of the bladder is a very rare disorder that accounts for 0.43% of all bladder neoplasms. Although the pathophysiology of the bladder leiomyoma is unknown, there are some theories in it. The patients can be asymptomatic; and clinical symptoms, when present, are associated with the tumor size and location. Imaging techniques such as ultrasonography, intravenous urography, computed tomography, and magnetic resonance imaging are helpful but definitive diagnosis is made by histopathological examination. Surgical resection of tumor with transurethral, open, laparoscopic and robotic approaches is the main treatment. We present a case of leiomyoma of the bladder in an adult male patient.

  8. Radiation responses of human bladder cancer assessed in vitro or as xenografts in immune-deprived mice

    International Nuclear Information System (INIS)

    Tannock, I.; Choo, B.; Buick, R.

    1984-01-01

    The response to radiation of cells derived from transitional cell carcinoma (TCC) of the human bladder has been studied. In vitro radiation survival curves for two established cell lines, RT-4 and MGH-U1, and for a cell line HB-10 derived recently from biopsy of a metastatic lymph node were characterized by values of D 0 and anti n in the range of 1.1-1.5 Gy and 2-7 respectively. The oxygen enhancement ratio of HB-10 cells was 2.8. Xenografts derived from the line HB-10 were irradiated in vivo under both aerobic and hypoxic conditions and cell survival was assessed in agar. Both aerobic and hypoxic survival curves were similar to that obtained for irradiation of hypoxic HB-10 cells in culture. Another tumor line, HB-15, derived from a cystoscopic biopsy of primary TCC, was maintained by transplantation of xenografts. Regrowth curves for HB-15 xenografts after radiation doses of 10 or 20 Gy were parallel to the growth curve for untreated controls but with volume reduced by factors of about 5 and 20 respectively. Cells derived from TCC of the human bladder exhibit parameters of radiation survival similar to those of other mammalian cells, and that xenografts derived from such cells contain a high proportion of hypoxic cells

  9. 1α,25(OH)2D3 differentially regulates miRNA expression in human bladder cancer cells.

    Science.gov (United States)

    Ma, Yingyu; Hu, Qiang; Luo, Wei; Pratt, Rachel N; Glenn, Sean T; Liu, Song; Trump, Donald L; Johnson, Candace S

    2015-04-01

    Bladder cancer is the fourth most commonly diagnosed cancer in men and eighth leading cause of cancer-related death in the US. Epidemiological and experimental studies strongly suggest a role for 1α,25(OH)2D3 in cancer prevention and treatment. The antitumor activities of 1α,25(OH)2D3 are mediated by the induction of cell cycle arrest, apoptosis, differentiation and the inhibition of angiogenesis and metastasis. miRNAs play important regulatory roles in cancer development and progression. However, the role of 1α,25(OH)2D3 in the regulation of miRNA expression and the potential impact in bladder cancer has not been investigated. Therefore, we studied 1α,25(OH)2D3-regulated miRNA expression profiles in human bladder cancer cell line 253J and the highly tumorigenic and metastatic derivative line 253J-BV by miRNA qPCR panels. 253J and 253J-BV cells express endogenous vitamin D receptor (VDR), which can be further induced by 1α,25(OH)2D3. VDR target gene 24-hydroxylase was induced by 1α,25(OH)2D3 in both cell lines, indicating functional 1α,25(OH)2D3 signaling. The miRNA qPCR panel assay results showed that 253J and 253J-BV cells have distinct miRNA expression profiles. Further, 1α,25(OH)2D3 differentially regulated miRNA expression profiles in 253J and 253J-BV cells in a dynamic manner. Pathway analysis of the miRNA target genes revealed distinct patterns of contribution to the molecular functions and biological processes in the two cell lines. In conclusion, 1α,25(OH)2D3 differentially regulates the expression of miRNAs, which may contribute to distinct biological functions, in human bladder 253J and 253J-BV cells. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Charles H Hubscher

    Full Text Available Locomotor training (LT as a therapeutic intervention following spinal cord injury (SCI is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs' pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury.Prospective cohort study; pilot trial with small sample size.Eight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart.Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants.These results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively

  11. Evaluating Evidence for Association of Human Bladder Cancer with Drinking-Water Chlorination Disinfection By-Products.

    Science.gov (United States)

    Hrudey, Steve E; Backer, Lorraine C; Humpage, Andrew R; Krasner, Stuart W; Michaud, Dominique S; Moore, Lee E; Singer, Philip C; Stanford, Benjamin D

    2015-01-01

    Exposure to chlorination disinfection by-products (CxDBPs) is prevalent in populations using chlorination-based methods to disinfect public water supplies. Multifaceted research has been directed for decades to identify, characterize, and understand the toxicology of these compounds, control and minimize their formation, and conduct epidemiologic studies related to exposure. Urinary bladder cancer has been the health risk most consistently associated with CxDBPs in epidemiologic studies. An international workshop was held to (1) discuss the qualitative strengths and limitations that inform the association between bladder cancer and CxDBPs in the context of possible causation, (2) identify knowledge gaps for this topic in relation to chlorine/chloramine-based disinfection practice(s) in the United States, and (3) assess the evidence for informing risk management. Epidemiological evidence linking exposures to CxDBPs in drinking water to human bladder cancer risk provides insight into causality. However, because of imprecise, inaccurate, or incomplete estimation of CxDBPs levels in epidemiologic studies, translation from hazard identification directly to risk management and regulatory policy for CxDBPs can be challenging. Quantitative risk estimates derived from toxicological risk assessment for CxDBPs currently cannot be reconciled with those from epidemiologic studies, notwithstanding the complexities involved, making regulatory interpretation difficult. Evidence presented here has both strengths and limitations that require additional studies to resolve and improve the understanding of exposure response relationships. Replication of epidemiologic findings in independent populations with further elaboration of exposure assessment is needed to strengthen the knowledge base needed to better inform effective regulatory approaches.

  12. Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury

    Science.gov (United States)

    Williams, Carolyn S.; Montgomery, Lynnette R.; Willhite, Andrea M.; Angeli, Claudia A.; Harkema, Susan J.

    2018-01-01

    Objective Locomotor training (LT) as a therapeutic intervention following spinal cord injury (SCI) is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs’ pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury). Study design Prospective cohort study; pilot trial with small sample size. Methods Eight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine) research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart. Results Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants. Conclusions These results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task

  13. Inhibition of inducible heat shock protein-70 (hsp72 enhances bortezomib-induced cell death in human bladder cancer cells.

    Directory of Open Access Journals (Sweden)

    Wei Qi

    Full Text Available The proteasome inhibitor bortezomib (Velcade is a promising new agent for bladder cancer therapy, but inducible cytoprotective mechanisms may limit its potential efficacy. We used whole genome mRNA expression profiling to study the effects of bortezomib on stress-induced gene expression in a panel of human bladder cancer cell lines. Bortezomib induced strong upregulation of the inducible HSP70 isoforms HSPA1A and HSPA1B isoforms of Hsp72 in 253J B-V and SW780 (HSPA1A(high cells, but only induced the HSPA1B isoform in UM-UC10 and UM-UC13 (HSPA1A(low cells. Bortezomib stimulated the binding of heat shock factor-1 (HSF1 to the HSPA1A promoter in 253JB-V but not in UM-UC13 cells. Methylation-specific PCR revealed that the HSPA1A promoter was methylated in the HSPA1A(low cell lines (UM-UC10 and UM-UC13, and exposure to the chromatin demethylating agent 5-aza-2'-deoxycytidine restored HSPA1A expression. Overexpression of Hsp72 promoted bortezomib resistance in the UM-UC10 and UM-UC13 cells, whereas transient knockdown of HSPA1B further sensitized these cells to bortezomib, and exposure to the chemical HSF1 inhibitor KNK-437 promoted bortezomib sensitivity in the 253J B-V cells. Finally, shRNA-mediated stable knockdown of Hsp72 in 253J B-V promoted sensitivity to bortezomib in vitro and in tumor xenografts in vivo. Together, our results provide proof-of-concept for using Hsp72 inhibitors to promote bortezomib sensitivity in bladder cancers and suggest that selective targeting of HSPA1B could produce synthetic lethality in tumors that display HSPA1A promoter methylation.

  14. Evaluating Evidence for Association of Human Bladder Cancer with Drinking-Water Chlorination Disinfection By-Products

    Science.gov (United States)

    Hrudey, Steve E.; Backer, Lorraine C.; Humpage, Andrew R.; Krasner, Stuart W.; Michaud, Dominique S.; Moore, Lee E.; Singer, Philip C.; Stanford, Benjamin D.

    2015-01-01

    Exposure to chlorination disinfection by-products (CxDBPs) is prevalent in populations using chlorination-based methods to disinfect public water supplies. Multifaceted research has been directed for decades to identify, characterize, and understand the toxicology of these compounds, control and minimize their formation, and conduct epidemiologic studies related to exposure. Urinary bladder cancer has been the health risk most consistently associated with CxDBPs in epidemiologic studies. An international workshop was held to (1) discuss the qualitative strengths and limitations that inform the association between bladder cancer and CxDBPs in the context of possible causation, (2) identify knowledge gaps for this topic in relation to chlorine/chloramine-based disinfection practice(s) in the United States, and (3) assess the evidence for informing risk management. Epidemiological evidence linking exposures to CxDBPs in drinking water to human bladder cancer risk provides insight into causality. However, because of imprecise, inaccurate, or incomplete estimation of CxDBPs levels in epidemiologic studies, translation from hazard identification directly to risk management and regulatory policy for CxDBPs can be challenging. Quantitative risk estimates derived from toxicological risk assessment for CxDBPs currently cannot be reconciled with those from epidemiologic studies, notwithstanding the complexities involved, making regulatory interpretation difficult. Evidence presented here has both strengths and limitations that require additional studies to resolve and improve the understanding of exposure response relationships. Replication of epidemiologic findings in independent populations with further elaboration of exposure assessment is needed to strengthen the knowledge base needed to better inform effective regulatory approaches. PMID:26309063

  15. Herbal tea extract combined with light-induced significant in vitro cytotoxicity of human bladder cancer cells

    Science.gov (United States)

    Nseyo, Unyime; Kim, Albert; Stavropoulos, Nicholas E.; Skalkos, Dimitris; Nseyo, U. U.; Chung, Theodore D.

    2005-04-01

    The anti-inflammatory, anti-microbial, antiviral, and antidepressant activities of the Greek herb, Hypericum Perforatum L, HP L, have been attributed to the total extract or single constituents. We investigated the use of the extract,specifically of the polar methanolic fraction (PMF) of Epirus"HPL in photodynamic therapy (PDT) alone and in combination with recombinant Interferon-a2b (IFN) and gemcitabine (GCB) in the treatment of human bladder cancer cells. The PMF was extracted from the dry herb with methanol, followed by liquid-liquid extraction with petroleum ether. T-24 bladder cancer cells were plated (105 cells/well) and placed in the incubator (370 C, 5%CO) for 24 hours prior to addition of drugs. PMF 60ug/ml was added and incubation continued. After 24 hours, the cells were subjected to laser light (630nm) treatment with 0, 1, 4 and 8 Joules. After reincubation for 24 hours, IFN, (50,000 IU) or GCB, (2ug/ml) was added to the PDT-treated cells. After this incubation cell survival was assessed by the MTT assay. PMF-PDT alone-induced percent cell kill of 0%, 8%, 44% and 80% versus 31%, 64 and 86 % for PMF-PDT and IFN, versus 63%, 80% and 88% for MPF-PDT plus GCB at 1, 2, 4 and 8 Joules respectively. IFN and GCB induced 20% and 53% cell kill respectively. Our data suggest that MPF may be an effective agent for in vitro photodynamic therapy. PMF-PDT combined with Intron A, or gemcitabine achieved improved kill of cultured bladder cancer cells. Confirmation of these results in preclinical studies may lead to clinical trials.

  16. Functional and molecular characterization of kinin B1 and B 2 receptors in human bladder cancer: implication of the PI3Kγ pathway.

    Science.gov (United States)

    Sgnaolin, V; Pereira, T C B; Bogo, M R; Zanin, R; Battastini, A M O; Morrone, F B; Campos, M M

    2013-08-01

    Kinins and their receptors have been recently implicated in cancer. Using functional and molecular approaches, we investigated the relevance of kinin B1 and B2 receptors in bladder cancer. Functional studies were conducted using bladder cancer cell lines, and human biopsies were employed for molecular studies. Both B1 des-Arg(9)-BK and B2 BK receptor agonists stimulated the proliferation of grade 3-derived T24 bladder cancer cells. Furthermore, treatment with B1 and B2 receptor antagonists (SSR240612 and HOE140) markedly inhibited the proliferation of T24 cells. Only higher concentrations of BK increased the proliferation of the grade 1 bladder cancer cell line RT4, while des-Arg(9)-BK completely failed to induce its proliferation. Real-time PCR revealed that the mRNA expression of kinin receptors, particularly B1 receptors, was increased in T24 cells relative to RT4 cells. Data from bladder cancer human biopsies revealed that B1 receptor expression was increased in all tumor samples and under conditions of chronic inflammation. We also show novel evidence demonstrating that the pharmacological inhibition of PI3Kγ (phosphatidylinositol 3-kinase) with AS252424, concentration-dependently reduced T24 cell proliferation induced by BK or des-Arg(9)-BK. Finally, the incubation of T24 cells with kinin agonists led to a marked activation of the PI3K/AKT and ERK 1/2 signaling pathways, whereas p38 MAP kinase remained unaffected. Kinin receptors, especially B1 receptors, appear to be implicated in bladder cancer progression. It is tempting to suggest that selective kinin antagonists might represent potential alternative therapies for bladder cancer.

  17. Compensatory Paracrine Mechanisms That Define The Urothelial Response to Injury in Partial Bladder Outlet Obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Bassuk, James; Lendvay, Thomas S.; Sweet, Robert; Han, Chang-Hee; Soygur, Tarkan; Cheng, Jan-Fang; Plaire, J. Chadwick; Charleston, Jay S.; Charleston, Lynne B.; Bagai, Shelly; Cochrane, Kimberly; Rubio, Eric; Bassuk, James A.; Fuchs, Elaine

    2007-06-21

    Diseases and conditions affecting the lower urinary tract are a leading cause of dysfunctional sexual health, incontinence, infection, and kidney failure. The growth, differentiation, and repair of the bladder's epithelial lining are regulated, in part, by fibroblast growth factor (FGF)-7 and -10 via a paracrine cascade originating in the mesenchyme (lamina propria) and targeting the receptor for FGF-7 and -10 within the transitional epithelium (urothelium). The FGF-7 gene is located at the 15q15-q21.1 locus on chromosome 15 and four exons generate a 3.852-kb mRNA. Five duplicated FGF-7 gene sequences that localized to chromosome 9 were predicted not to generate functional protein products, thus validating the use of FGF-7-null mice as an experimental model. Recombinant FGF-7 and -10 induced proliferation of human urothelial cells in vitro and transitional epithelium of wild-type and FGF-7-null mice in vivo.To determine the extent that induction of urothelial cell proliferation during the bladder response to injury is dependent on FGF-7, an animal model of partial bladder outlet obstruction was developed. Unbiased stereology was used to measure the percentage of proliferating urothelial cells between obstructed groups of wild-type and FGF-7-null mice. The stereological analysis indicated that a statistical significant difference did not exist between the two groups, suggesting that FGF-7 is not essential for urothelial cell proliferation in response to partial outlet obstruction. In contrast, a significant increase in FGF-10 expression was observed in the obstructed FGF-7-null group, indicating that the compensatory pathway that functions in this model results in urothelial repair.

  18. Effects of Physiotherapy in the Treatment of Neurogenic Bladder in Patients Infected With Human T-Lymphotropic Virus 1.

    Science.gov (United States)

    Andrade, Rosana C P; Neto, José A; Andrade, Luciana; Oliveira, Tatiane S; Santos, Dislene N; Oliveira, Cassius J V; Prado, Márcio J; Carvalho, Edgar M

    2016-03-01

    To evaluate the efficacy of physiotherapy for urinary manifestations in patients with human T-lymphotropic virus 1-associated lower urinary tract dysfunction. Open clinical trial was conducted with 21 patients attending the physiotherapy clinic of the Hospital Universitário, Bahia, Brazil. Combinations of behavioral therapy, perineal exercises, and intravaginal or intra-anal electrical stimulation were used. The mean age was 54 ± 12 years and 67% were female. After treatment, there was an improvement in symptoms of urinary urgency, frequency, incontinence, nocturia, and in the sensation of incomplete emptying (P Physiotherapy was effective in cases of human T-lymphotropic virus 1-associated neurogenic bladder, reducing symptoms, increasing perineal muscle strength, and improving urodynamic parameters and quality of life. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Photodynamic management of bladder cancer

    Science.gov (United States)

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

    2009-06-01

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

  20. Transplanted Human Stem Cell-Derived Interneuron Precursors Mitigate Mouse Bladder Dysfunction and Central Neuropathic Pain after Spinal Cord Injury.

    Science.gov (United States)

    Fandel, Thomas M; Trivedi, Alpa; Nicholas, Cory R; Zhang, Haoqian; Chen, Jiadong; Martinez, Aida F; Noble-Haeusslein, Linda J; Kriegstein, Arnold R

    2016-10-06

    Neuropathic pain and bladder dysfunction represent significant quality-of-life issues for many spinal cord injury patients. Loss of GABAergic tone in the injured spinal cord may contribute to the emergence of these symptoms. Previous studies have shown that transplantation of rodent inhibitory interneuron precursors from the medial ganglionic eminence (MGE) enhances GABAergic signaling in the brain and spinal cord. Here we look at whether transplanted MGE-like cells derived from human embryonic stem cells (hESC-MGEs) can mitigate the pathological effects of spinal cord injury. We find that 6 months after transplantation into injured mouse spinal cords, hESC-MGEs differentiate into GABAergic neuron subtypes and receive synaptic inputs, suggesting functional integration into host spinal cord. Moreover, the transplanted animals show improved bladder function and mitigation of pain-related symptoms. Our results therefore suggest that this approach may be a valuable strategy for ameliorating the adverse effects of spinal cord injury. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Shanshan Wang

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

  2. Overexpression of high mobility group box 1 contributes to progressive clinicopathological features and poor prognosis of human bladder urothelial carcinoma

    Directory of Open Access Journals (Sweden)

    Huang CK

    2018-04-01

    Full Text Available Changkun Huang,* Zhichao Huang,* Xiaokun Zhao, Yinhuai Wang, Hongqing Zhao, Zhaohui Zhong, Lang Wang Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China *These authors contributed equally to this work Background: High mobility group box 1 (HMGB1, a versatile protein with intranuclear and extracellular functions, plays an important role in a variety of human cancers. However, the clinical/prognostic significance of HMGB1 expression in human bladder urothelial carcinoma (BUC remains unclear. The aim of this study was to investigate the HMGB1 expression in human BUC with regard to its clinical and prognostic significance.Patients and methods: HMGB1 mRNA and protein expressions in tumor and paired normal bladder tissues were detected in 20 BUC cases by quantitative real-time polymerase chain reaction (qRT-PCR and Western blot. HMGB1 protein expression in 165 primary BUC tissues was evaluated by immunohistochemistry (IHC, and its correlations with clinicopathological characteristics and prognosis were also analyzed. Student’s t-test, χ2 test, Kaplan–Meier plots, and Cox proportional hazard regression model were performed to analyze the data. Results: By using qRT-PCR and Western blot, the upregulated expression of HMGB1 mRNA and protein was detected in BUC, compared with paired normal tissue (P<0.05. By using IHC, high HMGB1 expression was examined in 84 of 165 (51.0% BUC cases. High HMGB1 expression was significantly correlated with poorer differentiation and higher T and N classification (all P<0.05. Univariate analysis showed that high HMGB1 expression was significantly associated with a shortened patients’ overall survival (OS and disease-free survival (DFS; both P<0.001. In different subgroups of BUC patients, HMGB1 expression was a prognostic factor in patients with different histological grades or T classification (all P<0.05, pN− (both P<0.001 for OS and DFS, and

  3. Human Alpha Defensin 5 Expression in the Human Kidney and Urinary Tract

    Science.gov (United States)

    Porter, Edith; Bevins, Charles L.; DiRosario, Julianne; Becknell, Brian; Wang, Huanyu

    2012-01-01

    Background The mechanisms that maintain sterility in the urinary tract are incompletely understood. Recent studies have implicated the importance of antimicrobial peptides (AMP) in protecting the urinary tract from infection. Here, we characterize the expression and relevance of the AMP human alpha-defensin 5 (HD5) in the human kidney and urinary tract in normal and infected subjects. Methodology/Principal Findings Using RNA isolated from human kidney, ureter, and bladder tissue, we performed quantitative real-time PCR to show that DEFA5, the gene encoding HD5, is constitutively expressed throughout the urinary tract. With pyelonephritis, DEFA5 expression significantly increased in the kidney. Using immunoblot analysis, HD5 production also increased with pyelonephritis. Immunostaining localized HD5 to the urothelium of the bladder and ureter. In the kidney, HD5 was primarily produced in the distal nephron and collecting tubules. Using immunoblot and ELISA assays, HD5 was not routinely detected in non-infected human urine samples while mean urinary HD5 production increased with E.coli urinary tract infection. Conclusions/Significance DEFA5 is expressed throughout the urinary tract in non-infected subjects. Specifically, HD5 is expressed throughout the urothelium of the lower urinary tract and in the collecting tubules of the kidney. With infection, HD5 expression increases in the kidney and levels become detectable in the urine. To our knowledge, our findings represent the first to quantitate HD5 expression and production in the human kidney. Moreover, this is the first report to detect the presence of HD5 in infected urine samples. Our results suggest that HD5 may have an important role in maintaining urinary tract sterility. PMID:22359618

  4. [Synergetic killing effects of external magnetic fields combined with porphyrin-dextran magnetic nanoparticles on the human bladder cancer cells].

    Science.gov (United States)

    Luo, Dao-sheng; Mi, Qi-wu; Meng, Xiang-jun; Gao, Yong; Dai, Yu-ping; Deng, Chun-hua

    2012-08-18

    To study the synergetic killing effects of external magnetic fields combined with the photodynamic action of porphyrin-dextran iron oxide magnetic nanoparticles (PDMN) on human bladder cancer cells in vitro. The PDMN were produced by using the chemical co-precipitation and redox process and the physicochemical properties were characterized. Methyl thiazolyl tetrazolium (MTT) and flow cytometry were used to determine the effects of photodynamic therapy of PDMN combined with external pulsed electromagnetic fields (5 mT) on killing human bladder cancer BIU-87 cells respectively. The diameters of PDMN were 10-15 nm and the saturation magnetization was 0.20 emu/g. Effective diameter of PDMN was 94.8 nm. PDMN could remarkably inhibit the proliferation and induce the obvious apoptosis of BIU-87 cells, and the rates of growth inhibition and apoptosis were (17.61±2.73)% and (24.53±5.74)% respectively. Moreover, external pulsed electromagnetic fields (5 mT) could also suppress the proliferation and induce apoptosis of BIU-87 cells. Furthermore, the photodynamic action of PDMN combined with external magnetic fields significantly inhibited the proliferation and promote apoptosis of BIU-87 cells, and the rates of growth inhibition and apoptosis was (28.11±4.25)% and (24.53±5.74)%, respectively, which were significantly higher than those of other groups (Peffectively inhibit proliferation and induce apoptosis of BIU-87 cells. Moreover, these effects on BIU-87 cells could be strengthened by the combination with external magnetic fields.

  5. Reduced glucocorticoid receptor expression predicts bladder tumor recurrence and progression.

    Science.gov (United States)

    Ishiguro, Hitoshi; Kawahara, Takashi; Zheng, Yichun; Netto, George J; Miyamoto, Hiroshi

    2014-08-01

    To assess the levels of glucocorticoid receptor (GR) expression in bladder tumors because the status and its prognostic value remain largely unknown. We immunohistochemically stained for GR in bladder tumor and matched non-neoplastic bladder tissue specimens. Overall, GR was positive in 129 (87%) of 149 urothelial tumors, which was significantly (P=.026) lower than in non-neoplastic urothelium (90 [96%] of 94). Forty-two (79%) of 53 low-grade tumors vs 45 (47%) of 96 high-grade carcinomas (Pcancer-specific survival of MI tumors (P=.067). Multivariate analysis identified low GR expression as a strong predictor for recurrence of NMI tumors (P=.034). GR expression was downregulated in bladder tumors compared with nonneoplastic bladder tumors and in high-grade/MI tumors compared with low-grade/NMI tumors. Decreased expression of GR, as an independent prognosticator, predicted recurrence of NMI tumors. These results support experimental evidence suggesting an inhibitory role of GR signals in bladder cancer outgrowth. Copyright© by the American Society for Clinical Pathology.

  6. Overactive Bladder

    Science.gov (United States)

    ... especially if your symptoms disrupt your work schedule, social interactions and everyday activities. Causes Normal bladder function The ... fills, nerve signals sent to your brain eventually trigger the need to urinate. When you urinate, nerve ...

  7. Neurogenic bladder

    Science.gov (United States)

    ... cause skin to break down and lead to pressure sores Kidney damage if the bladder becomes too full, ... dysfunction; NBSD Patient Instructions Multiple sclerosis - discharge Preventing pressure ulcers Images Voiding cystourethrogram References Chapple CR, Osman NI. ...

  8. Bladder cancer

    Science.gov (United States)

    ... Dye workers, rubber workers, aluminum workers, leather workers, truck drivers, and pesticide applicators are at the highest ... examining the inside of the bladder with a camera), with biopsy Intravenous pyelogram - IVP Pelvic CT scan ...

  9. 17-Allylamino-17-demethoxygeldanamycin induces downregulation of critical Hsp90 protein clients and results in cell cycle arrest and apoptosis of human urinary bladder cancer cells

    International Nuclear Information System (INIS)

    Karkoulis, Panagiotis K; Stravopodis, Dimitrios J; Margaritis, Lukas H; Voutsinas, Gerassimos E

    2010-01-01

    17-Allylamino-17-demethoxygeldanamycin (17-AAG), a benzoquinone ansamycin antibiotic, specifically targets heat shock protein 90 (Hsp90) and interferes with its function as a molecular chaperone that maintains the structural and functional integrity of various protein clients involved in cellular signaling. In this study, we have investigated the effect of 17-AAG on the regulation of Hsp90-dependent signaling pathways directly implicated in cell cycle progression, survival and motility of human urinary bladder cancer cell lines. We have used MTT-based assays, FACS analysis, Western blotting, semi-quantitative RT-PCR, immunocytochemistry and scratch-wound assay in RT4, RT112 and T24 human urinary bladder cancer cell lines. We have demonstrated that, upon 17-AAG treatment, bladder cancer cells are arrested in the G1 phase of the cell cycle and eventually undergo apoptotic cell death in a dose-dependent manner. Furthermore, 17-AAG administration was shown to induce a pronounced downregulation of multiple Hsp90 protein clients and other downstream effectors, such as IGF-IR, Akt, IKK-α, IKK-β, FOXO1, ERK1/2 and c-Met, resulting in sequestration-mediated inactivation of NF-κB, reduced cell proliferation and decline of cell motility. In total, we have clearly evinced a dose-dependent and cell type-specific effect of 17-AAG on cell cycle progression, survival and motility of human bladder cancer cells, due to downregulation of multiple Hsp90 clients and subsequent disruption of signaling integrity

  10. Keratin, luminal epithelial antigen and carcinoembryonic antigen in human urinary bladder carcinomas. An immunohistochemical study.

    Science.gov (United States)

    Nathrath, W B; Arnholdt, H; Wilson, P D

    1982-01-01

    14 urinary bladder carcinomas of all main types were investigated with antisera to "broad spectrum keratin" (aK), "luminal epithelial antigen" (aLEA) and carcinoembryonic antigen (aCEA), using an indirect immunoperoxidase method on formalin fixed paraffin embedded sections. Keratin and LEA were both present in normal transitional epithelium, papilloma and carcinoma in situ whereas CEA was absent. Transitional cell carcinomas reacted with both aK and aLEA whereas CEA was seen only in a few foci. In squamous metaplasia and squamous carcinoma reaction with aK was particularly strong, while LEA was almost lacking and CEA was present in necrotic centres. In adenocarcinomas aK and aLEA reacted equally while aCEA reacted only on the surface.

  11. Rhodamine dyes as potential agents for photochemotherapy of cancer in human bladder carcinoma cells

    International Nuclear Information System (INIS)

    Shea, C.R.; Chen, N.; Wimberly, J.; Hasan, T.

    1989-01-01

    The phototoxicity in vitro of rhodamine 123 and tetrabromo rhodamine 123 (TBR) was compared, in order to assess their photochemotherapeutic potential. Exposure to 514.5-nm radiation from an argon ion laser caused phototoxicity in MGH-U1 bladder carcinoma cells previously treated with either dye at 10 microM for 30 min. As assessed by colony formation and cellular morphology, TBR was markedly more phototoxic than rhodamine 123, reflecting increased intersystem crossing of TBR to the triplet manifold via spin-orbital coupling induced by the heavy bromine atoms. Photoreactions of TBR very efficiently generated singlet oxygen ( 1 O 2 ) in solution; furthermore, irradiation of TBR-treated cells was significantly more toxic when performed in the presence of deuterium oxide, an enhancer of damage caused by 1 O 2 . Retention of fluorescence in TBR-treated cells was enhanced by irradiation, indicating that a stable photoproduct may be formed in reaction with cellular components

  12. Androgenic dependence of exophytic tumor growth in a transgenic mouse model of bladder cancer: a role for thrombospondin-1

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    Yao Jorge L

    2008-04-01

    Full Text Available Abstract Background Steroid hormones influence mitogenic signaling pathways, apoptosis, and cell cycle checkpoints, and it has long been known that incidence of bladder cancer (BC in men is several times greater than in women, a difference that cannot be attributed to environmental or lifestyle factors alone. Castration reduces incidence of chemically-induced BC in rodents. It is unclear if this effect is due to hormonal influences on activation/deactivation of carcinogens or a direct effect on urothelial cell proliferation or other malignant processes. We examined the effect of castration on BC growth in UPII-SV40T transgenic mice, which express SV40 T antigen specifically in urothelium and reliably develop BC. Furthermore, because BC growth in UPII-SV40T mice is exophytic, we speculated BC growth was dependent on angiogenesis and angiogenesis was, in turn, androgen responsive. Methods Flat panel detector-based cone beam computed tomography (FPDCT was used to longitudinally measure exophytic BC growth in UPII-SV40T male mice sham-operated, castrated, or castrated and supplemented with dihydrotestosterone (DHT. Human normal bladder and BC biopsies and mouse bladder were examined quantitatively for thrombospondin-1 (TSP1 protein expression. Results Mice castrated at 24 weeks of age had decreased BC volumes at 32 weeks compared to intact mice (p = 0.0071 and castrated mice administered DHT (p = 0.0233; one-way ANOVA, JMP 6.0.3, SAS Institute, Inc.. Bladder cancer cell lines responded to DHT treatment with increased proliferation, regardless of androgen receptor expression levels. TSP1, an anti-angiogenic factor whose expression is inhibited by androgens, had decreased expression in bladders of UPII-SV40T mice compared to wild-type. Castration increased TSP1 levels in UPII-SV40T mice compared to intact mice. TSP1 protein expression was higher in 8 of 10 human bladder biopsies of normal versus malignant tissue from the same patients. Conclusion

  13. Disulfide high mobility group box-1 causes bladder pain through bladder Toll-like receptor 4.

    Science.gov (United States)

    Ma, Fei; Kouzoukas, Dimitrios E; Meyer-Siegler, Katherine L; Westlund, Karin N; Hunt, David E; Vera, Pedro L

    2017-05-25

    Bladder pain is a prominent symptom in several urological conditions (e.g. infection, painful bladder syndrome/interstitial cystitis, cancer). Understanding the mechanism of bladder pain is important, particularly when the pain is not accompanied by bladder pathology. Stimulation of protease activated receptor 4 (PAR4) in the urothelium results in bladder pain through release of urothelial high mobility group box-1 (HMGB1). HGMB1 has two functionally active redox states (disulfide and all-thiol) and it is not known which form elicits bladder pain. Therefore, we investigated whether intravesical administration of specific HMGB1 redox forms caused abdominal mechanical hypersensitivity, micturition changes, and bladder inflammation in female C57BL/6 mice 24 hours post-administration. Moreover, we determined which of the specific HMGB1 receptors, Toll-like receptor 4 (TLR4) or receptor for advanced glycation end products (RAGE), mediate HMGB1-induced changes. Disulfide HMGB1 elicited abdominal mechanical hypersensitivity 24 hours after intravesical (5, 10, 20 μg/150 μl) instillation. In contrast, all-thiol HMGB1 did not produce abdominal mechanical hypersensitivity in any of the doses tested (1, 2, 5, 10, 20 μg/150 μl). Both HMGB1 redox forms caused micturition changes only at the highest dose tested (20 μg/150 μl) while eliciting mild bladder edema and reactive changes at all doses. We subsequently tested whether the effects of intravesical disulfide HMGB1 (10 μg/150 μl; a dose that did not produce inflammation) were prevented by systemic (i.p.) or local (intravesical) administration of either a TLR4 antagonist (TAK-242) or a RAGE antagonist (FPS-ZM1). Systemic administration of either TAK-242 (3 mg/kg) or FPS-ZM1 (10 mg/kg) prevented HMGB1 induced abdominal mechanical hypersensitivity while only intravesical TLR4 antagonist pretreatment (1.5 mg/ml; not RAGE) had this effect. The disulfide form of HMGB1 mediates bladder pain directly (not

  14. Bladder Cancer Advocacy Network

    Science.gov (United States)

    ... Grants Bladder Cancer Think Tank Bladder Cancer Research Network Bladder Cancer Genomics Consortium Get Involved Ways to ... us? Who we are The Bladder Cancer Advocacy Network (BCAN) is a community of patients, caregivers, survivors, ...

  15. Antitumor potential of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H-pyrazoles in human bladder cancer cells.

    Science.gov (United States)

    Tessmann, Josiane Weber; Buss, Julieti; Begnini, Karine Rech; Berneira, Lucas Moraes; Paula, Favero Reisdorfer; de Pereira, Claudio Martin Pereira; Collares, Tiago; Seixas, Fabiana Kömmling

    2017-10-01

    Bladder cancer is a genitourinary malignant disease common worldwide. Current chemotherapy is often limited mainly due to toxicity and drug resistance. Thus, there is a continued need to discover new therapies. Recently evidences shows that pyrazoline derivatives are promising antitumor agents in many types of cancers, but there are no studies with bladder cancer. In order to find potent and novel chemotherapy drugs for bladder cancer, a series of pyrazoline derivatives 2a-2d were tested for their antitumor activity in two human bladder cancer cell lines 5647 and T24. The MTT assay showed that the compounds 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-1H-pyrazole (2a) and 1-thiocarbamoyl-5-(4-chlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazole (2c) decrease the cell viability of 5637 cells. Molecular modeling indicated that these compounds had a good oral bioavailability and low toxicities. Clonogenic assay and flow cytometric analysis were used to assess colony formation, apoptosis induction and cell cycle distribution. Overall, our results suggest that pyrazoline 2a and 2c, with the substituents hydrogen and chlorine respectively, may decrease cell viability and colony formation of bladder cancer 5637 cell line by inhibition of cell cycle progression, and for pyrazoline 2a, by induction of apoptosis. As indicated by the physicochemical properties of these compounds, the steric factor influences the activity. Therefore, these pyrazoline derivatives can be considered promising anticancer agents for the treatment of bladder cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Transcriptional and post-transcriptional upregulation of p27 mediates growth inhibition of isorhapontigenin (ISO) on human bladder cancer cells.

    Science.gov (United States)

    Jiang, Guosong; Huang, Chao; Li, Jingxia; Huang, Haishan; Wang, Jingjing; Li, Yawei; Xie, Fei; Jin, Honglei; Zhu, Junlan; Huang, Chuanshu

    2018-03-08

    There are few approved drugs available for the treatment of muscle-invasive bladder cancer (MIBC). Recently, we have demonstrated that isorhapontigenin (ISO), a new derivative isolated from the Chinese herb Gnetum cleistostachyum, effectively induces cell-cycle arrest at the G0/G1 phase and inhibits anchorage-independent cell growth through the miR-137/Sp1/cyclin D1 axis in human MIBC cells. Herein, we found that treatment of bladder cancer (BC) cells with ISO resulted in a significant upregulation of p27, which was also observed in ISO-treated mouse BCs that were induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Importantly, knockdown of p27 caused a decline in the ISO-induced G0-G1 growth arrest and reversed ISO suppression of anchorage-independent growth in BC cells. Mechanistic studies revealed that ISO promoted p27 expression at mRNA transcription level through increasing direct binding of forkhead box class O1 (FOXO1) to its promoter, while knockdown of FOXO1 attenuated ISO inhibition of BC cell growth. On the other hand, ISO upregulated the 3'-untranslated region (3'-UTR) activity of p27, which was accompanied by a reduction of miR-182 expression. In line with these observations, ectopic expression of miR-182 significantly blocked p27 3'-UTR activity, whereas mutation of the miR-182-binding site at p27 mRNA 3'-UTR effectively reversed this inhibition. Accordingly, ectopic expression of miR-182 also attenuated ISO upregulation of p27 expression and impaired ISO inhibition of BC cell growth. Our results not only provide novel insight into understanding of the underlying mechanism related to regulation of MIBC cell growth but also identify new roles and mechanisms underlying ISO inhibition of BC cell growth.

  17. Pathogenic and Diagnostic Potential of BLCA-1 and BLCA-4 Nuclear Proteins in Urothelial Cell Carcinoma of Human Bladder

    Directory of Open Access Journals (Sweden)

    Matteo Santoni

    2012-01-01

    Full Text Available Transitional cell carcinoma (TCC of the bladder is one of the most common malignancies of genitourinary tract. Patients with bladder cancer need a life-long surveillance, directly due to the relatively high recurrence rate of this tumor. The use of cystoscopy represents the gold standard for the followup of previously treated patients. Nevertheless, several factors, including cost and invasiveness, render cystoscopy not ideal for routine controls. Advances in the identification of specific alterations in the nuclear structure of bladder cancer cells have opened novel diagnostic landscapes. The members of nuclear matrix protein family BLCA-1 and BLCA-4, are currently under evaluation as bladder cancer urinary markers. They are involved in tumour cell proliferation, survival, and angiogenesis. In this paper, we illustrate the role of BLCA-1 and BLCA-4 in bladder carcinogenesis and their potential exploitation as biomarkers in this cancer.

  18. Effects of tumor necrosis factor-alpha and interferon-gamma on expressions of matrix metalloproteinase-2 and -9 in human bladder cancer cells.

    Science.gov (United States)

    Shin, K Y; Moon, H S; Park, H Y; Lee, T Y; Woo, Y N; Kim, H J; Lee, S J; Kong, G

    2000-10-31

    We have investigated the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon (INF-gamma), the potent Bacillus Calmette-Guerin (BCG)-induced cytokines on the production of MMP-2, MMP-9, TIMP-1, TIMP-2 and MT1-MMP in high grade human bladder cancer cell lines, T-24, J-82 and HT-1376 cell lines. MMP-2 expression and activity were decreased in T-24 cells treated with both cytokines in a dose dependent manner. However, J-82 cells treated with TNF-alpha and INF-gamma revealed dose dependent increases of MMP-9 expression and activity with similar baseline expression and activity of MMP-2. HT-1376 cells after exposure to TNF-alpha only enhanced the expression and activity of MMP-9. These results indicate that TNF-alpha and INF-gamma could regulate the production of MMP-2 or MMP-9 on bladder cancer cells and their patterns of regulation are cell specific. Furthermore, this diverse response of bladder cancer cells to TNF-alpha and INF-gamma suggests that BCG immunotherapy may enhance the invasiveness of bladder cancer in certain conditions with induction of MMPs.

  19. Characterization of a Murine Model of Bioequivalent Bladder Wound Healing and Repair Following Subtotal Cystectomy

    Directory of Open Access Journals (Sweden)

    Mona Zarifpour

    2017-05-01

    Full Text Available Previous work demonstrated restoration of a bioequivalent bladder within 8 weeks of removing the majority of the bladder (subtotal cystectomy or STC in rats. The goal of the present study was to extend our investigations of bladder repair to the murine model, to harness the power of mouse genetics to delineate the cellular and molecular mechanisms responsible for the observed robust bladder regrowth. Female C57 black mice underwent STC, and at 4, 8, and 12 weeks post-STC, bladder repair and function were assessed via cystometry, ex vivo pharmacologic organ bath studies, and T2-weighted magnetic resonance imaging (MRI. Histology was also performed to measure bladder wall thickness. We observed a time-dependent increase in bladder capacity (BC following STC, such that 8 and 12 weeks post-STC, BC and micturition volumes were indistinguishable from those of age-matched non-STC controls and significantly higher than observed at 4 weeks. MRI studies confirmed that bladder volume was indistinguishable within 3 months (11 weeks post-STC. Additionally, bladders emptied completely at all time points studied (i.e., no increases in residual volume, consistent with functional bladder repair. At 8 and 12 weeks post-STC, there were no significant differences in bladder wall thickness or in the different components (urothelium, lamina propria, or smooth muscle layers of the bladder wall compared with age-matched control animals. The maximal contractile response to pharmacological activation and electrical field stimulation increased over time in isolated tissue strips from repaired bladders but remained lower at all time points compared with controls. We have established and validated a murine model for the study of de novo organ repair that will allow for further mechanistic studies of this phenomenon after, for example, genetic manipulation.

  20. Distinct DNA methylation epigenotypes in bladder cancer from different Chinese sub-populations and its implication in cancer detection using voided urine

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    Tong Joanna HM

    2011-05-01

    Full Text Available Abstract Background Bladder cancer is the sixth most common cancer in the world and the incidence is particularly high in southwestern Taiwan. Previous studies have identified several tumor-related genes that are hypermethylated in bladder cancer; however the DNA methylation profile of bladder cancer in Taiwan is not fully understood. Methods In this study, we compared the DNA methylation profile of multiple tumor suppressor genes (APC, DAPK, E-cadherin, hMLH1, IRF8, p14, p15, RASSF1A, SFRP1 and SOCS-1 in bladder cancer patients from different Chinese sub-populations including Taiwan (104 cases, Hong Kong (82 cases and China (24 cases by MSP. Two normal human urothelium were also included as control. To investigate the diagnostic potential of using DNA methylation in non-invasive detection of bladder cancer, degree of methylation of DAPK, IRF8, p14, RASSF1A and SFRP1 was also accessed by quantitative MSP in urine samples from thirty bladder cancer patients and nineteen non-cancer controls. Results There were distinct DNA methylation epigenotypes among the different sub-populations. Further, samples from Taiwan and China demonstrated a bimodal distribution suggesting that CpG island methylator phentotype (CIMP is presented in bladder cancer. Moreover, the number of methylated genes in samples from Taiwan and Hong Kong were significantly correlated with histological grade (P SFRP1, IRF8, APC and RASSF1A were significantly associated with increased tumor grade, stage. Methylation of RASSF1A was associated with tumor recurrence. Patients with methylation of APC or RASSF1A were also significantly associated with shorter recurrence-free survival. For methylation detection in voided urine samples of cancer patients, the sensitivity and specificity of using any of the methylated genes (IRF8, p14 or sFRP1 by qMSP was 86.7% and 94.7%. Conclusions Our results indicate that there are distinct methylation epigenotypes among different Chinese sub

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    bladder cancer. RESULTS: The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling...... than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling...

  2. Transcriptional activation of the Axl and PDGFR-α by c-Met through a ras- and Src-independent mechanism in human bladder cancer

    International Nuclear Information System (INIS)

    Yeh, Chen-Yun; Tseng, Vincent S; Lee, Yuan-Chii G; Shen, Cheng-Huang; Chow, Nan-Haw; Liu, Hsiao-Sheng; Shin, Shin-Mei; Yeh, Hsuan-Heng; Wu, Tsung-Jung; Shin, Jyh-Wei; Chang, Tsuey-Yu; Raghavaraju, Giri; Lee, Chung-Ta; Chiang, Jung-Hsien

    2011-01-01

    A cross-talk between different receptor tyrosine kinases (RTKs) plays an important role in the pathogenesis of human cancers. Both NIH-Met5 and T24-Met3 cell lines harboring an inducible human c-Met gene were established. C-Met-related RTKs were screened by RTK microarray analysis. The cross-talk of RTKs was demonstrated by Western blotting and confirmed by small interfering RNA (siRNA) silencing, followed by elucidation of the underlying mechanism. The impact of this cross-talk on biological function was demonstrated by Trans-well migration assay. Finally, the potential clinical importance was examined in a cohort of 65 cases of locally advanced and metastatic bladder cancer patients. A positive association of Axl or platelet-derived growth factor receptor-alpha (PDGFR-α) with c-Met expression was demonstrated at translational level, and confirmed by specific siRNA knock-down. The transactivation of c-Met on Axl or PDGFR-α in vitro was through a ras- and Src-independent activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathway. In human bladder cancer, co-expression of these RTKs was associated with poor patient survival (p < 0.05), and overexpression of c-Met/Axl/PDGFR-α or c-Met alone showed the most significant correlation with poor survival (p < 0.01). In addition to c-Met, the cross-talk with Axl and/or PDGFR-α also contributes to the progression of human bladder cancer. Evaluation of Axl and PDGFR-α expression status may identify a subset of c-Met-positive bladder cancer patients who may require co-targeting therapy

  3. Transcriptional activation of the Axl and PDGFR-α by c-Met through a ras- and Src-independent mechanism in human bladder cancer

    Directory of Open Access Journals (Sweden)

    Tseng Vincent S

    2011-04-01

    Full Text Available Abstract Background A cross-talk between different receptor tyrosine kinases (RTKs plays an important role in the pathogenesis of human cancers. Methods Both NIH-Met5 and T24-Met3 cell lines harboring an inducible human c-Met gene were established. C-Met-related RTKs were screened by RTK microarray analysis. The cross-talk of RTKs was demonstrated by Western blotting and confirmed by small interfering RNA (siRNA silencing, followed by elucidation of the underlying mechanism. The impact of this cross-talk on biological function was demonstrated by Trans-well migration assay. Finally, the potential clinical importance was examined in a cohort of 65 cases of locally advanced and metastatic bladder cancer patients. Results A positive association of Axl or platelet-derived growth factor receptor-alpha (PDGFR-α with c-Met expression was demonstrated at translational level, and confirmed by specific siRNA knock-down. The transactivation of c-Met on Axl or PDGFR-α in vitro was through a ras- and Src-independent activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK pathway. In human bladder cancer, co-expression of these RTKs was associated with poor patient survival (p p Conclusions In addition to c-Met, the cross-talk with Axl and/or PDGFR-α also contributes to the progression of human bladder cancer. Evaluation of Axl and PDGFR-α expression status may identify a subset of c-Met-positive bladder cancer patients who may require co-targeting therapy.

  4. Bladder stones

    Science.gov (United States)

    The health care provider will perform a physical exam. This will also include a rectal exam. The exam may reveal an enlarged prostate or other problems. The following tests may be done: Bladder or pelvic x-ray Cystoscopy Urinalysis Urine culture (clean catch)

  5. Anti-oxidant activity and attenuation of bladder hyperactivity by the flavonoid compound kaempferol.

    Science.gov (United States)

    Huang, Yaw-Bin; Lin, Ming-Wei; Chao, Yun; Huang, Chi-Te; Tsai, Yi-Hung; Wu, Pao-Chu

    2014-01-01

    To evaluate the anti-oxidant activity of the flavonoid compound, kaempferol, and to examine its role in the suppression of oxidative stress and attenuation of bladder hyperactivity in a rat model of bladder injury. The anti-oxidative activity of kaempferol was examined in lipopolysaccharide-treated RAW264.7 macrophages by using flow cytometry. For in vivo studies, rats were pretreated with kaempferol or vehicle for 24 h. The rat urothelium was injured by the administration of protamine sulfate for 1.5 h and irritated by the subsequent infusion of potassium chloride for 4 h. Oxidative stress in the bladder tissue was assessed using chemiluminescence assay, and the bladder pressure was determination by cystomertrogram. Kaempferol significantly suppressed lipopolysaccharide-induced reactive oxygen species production in RAW264.7 rat macrophages. Exposure of the rat bladder to sequential infusion of protamine sulfate and potassium chloride induced bladder hyperactivity. Pretreatment with kaempferol, prevented the formation of reactive oxygen species and prolonged the intercontraction interval. Kaempferol suppresses oxidative stress and attenuates bladder hyperactivity caused by potassium chloride after protamine sulfate-induced bladder injury. © 2013 The Japanese Urological Association.

  6. Bee venom induces apoptosis through intracellular Ca2+ -modulated intrinsic death pathway in human bladder cancer cells.

    Science.gov (United States)

    Ip, Siu-Wan; Chu, Yung-Lin; Yu, Chun-Shu; Chen, Po-Yuan; Ho, Heng-Chien; Yang, Jai-Sing; Huang, Hui-Ying; Chueh, Fu-Shin; Lai, Tung-Yuan; Chung, Jing-Gung

    2012-01-01

    To focus on bee venom-induced apoptosis in human bladder cancer TSGH-8301 cells and to investigate its signaling pathway to ascertain whether intracellular calcium iron (Ca(2+)) is involved in this effect. Bee venom-induced cytotoxic effects, productions of reactive oxygen species and Ca(2+) and the level of mitochondrial membrane potential (ΔΨm) were analyzed by flow cytometry. Apoptosis-associated proteins were examined by Western blot analysis and confocal laser microscopy. Bee venom-induced cell morphological changes and decreased cell viability through the induction of apoptosis in TSGH-8301 cell were found. Bee venom promoted the protein levels of Bax, caspase-9, caspase-3 and endonuclease G. The enhancements of endoplasmic reticulum stress-related protein levels were shown in bee venom-provoked apoptosis of TSGH-8301 cells. Bee venom promoted the activities of caspase-3, caspase-8, and caspase-9, increased Ca(2+) release and decreased the level of ΔΨm. Co-localization of immunofluorescence analysis showed the releases of endonuclease G and apoptosis-inducing factor trafficking to nuclei for bee venom-mediated apoptosis. The images revealed evidence of nuclear condensation and formation of apoptotic bodies by 4',6-diamidino-2-phenylindole staining and DNA gel electrophoresis showed the DNA fragmentation in TSGH-8301 cells. Bee venom treatment induces both caspase-dependent and caspase-independent apoptotic death through intracellular Ca(2+) -modulated intrinsic death pathway in TSGH-8301 cells. © 2011 The Japanese Urological Association.

  7. Expression of Peroxisome Proferator-Activated Receptor γ (PPARγ in Human Transitional Bladder Cancer and its Role in Inducing Cell Death

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    You-Fei Guan

    1999-10-01

    Full Text Available The present study examined the expression and role of the thiazolidinedione (TZD-activated transcription factor, peroxisome proliferator-activated receptor γ (PPARγ, in human bladder cancers. In situ hybridization shows that PPARγ mRNA is highly expressed in all human transitional epithelial cell cancers (TCCa's studied (n=11. PPARγ was also expressed in five TCCa cell lines as determined by RNase protection assays and immunoblot. Retinoid X receptor α (RXRα, a 9-cis-retinoic acid stimulated (9-cis-RA heterodimeric partner of PPARγ, was also co-expressed in all TCCa tissues and cell lines. Treatment of the T24 bladder cancer cells with the TZD PPARγ agonist troglitazone, dramatically inhibited 3H-thymidine incorporation and induced cell death. Addition of the RXRα ligands, 9-cis-RA or LG100268, sensitized T24 bladder cancer cells to the lethal effect of troglitazone and two other PPARγ activators, ciglitazone and 15-deoxy-Δ12,14-PGJ2 (15dPGJ2. Troglitazone treatment increased expression of two cyclin-dependent kinase inhibitors, p21wAF1/CIP1 and p16INK4, reduced cyclin D1 expression, consistent with G1 arrest. Troglitazone also induced an endogenous PPARγ target gene in T24 cells, adipocyte-type fatty acid binding protein (A-FABP, the expression of which correlates with bladder cancer differentiation. In situ hybridization shows that A-FABP expression is localized to normal uroepithelial cells as well as some TCCa's. Taken together, these results demonstrate that PPARγ is expressed in human TCCa where it may play a role in regulating TCCa differentiation and survival, thereby providing a potential target for therapy of uroepithelial cancers.

  8. Repeated Treatments with Chitosan in Combination with Antibiotics Completely Eradicate Uropathogenic Escherichia coli From Infected Mouse Urinary Bladders.

    Science.gov (United States)

    Erman, Andreja; Hergouth, Veronika Križan; Blango, Matthew G; Kos, Mojca Kerec; Mulvey, Matthew A; Veranic, Peter

    2017-08-01

    Uropathogenic Escherichia coli (UPEC), the primary causative agents of urinary tract infections, colonize and invade the epithelial cells of the bladder urothelium. Infection of immature urothelial cells can result in the formation of persistent intracellular reservoirs that are refractory to antibiotic treatments. Previously, we defined a novel therapeutic strategy that used the bladder cell exfoliant chitosan to deplete UPEC reservoirs. However, although a single treatment of chitosan followed by ciprofloxacin administration had a marked effect on reducing UPEC titers within the bladder, this treatment failed to prevent relapsing bacteriuria. We show here that repeated use of chitosan in conjunction with the antibiotic ciprofloxacin completely eradicates UPEC from the urinary tract and prevents the development of relapsing bouts of bacteriuria. In addition, microscopy revealed rapid restoration of bladder integrity following chitosan treatment, indicating that chitosan can be used to effectively combat recalcitrant bladder infections without causing lasting harm to the urothelium. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  9. Microsatellite instability in bladder cancer

    DEFF Research Database (Denmark)

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

    1993-01-01

    Somatic instability at microsatellite repeats was detected in 6 of 200 transitional cell carcinomas of the bladder. Instabilities were apparent as changes in (GT)n repeat lengths on human chromosome 9 for four tumors and as alterations in a (CAG)n repeat in the androgen receptor gene on the X...... or larger (> 2 base pairs) alterations in repeat length. All six tumors were low stage (Ta-T1), suggesting that these alterations can occur early in bladder tumorigenesis....

  10. Novel Multisensor Probe for Monitoring Bladder Temperature During Locoregional Chemohyperthermia for Nonmuscle-Invasive Bladder Cancer: Technical Feasibility Study

    Science.gov (United States)

    Geijsen, Debby E.; Zum Vörde Sive Vörding, Paul J.; Schooneveldt, Gerben; Sijbrands, Jan; Hulshof, Maarten C.; de la Rosette, Jean; de Reijke, Theo M.; Crezee, Hans

    2013-01-01

    Abstract Background and Purpose: The effectiveness of locoregional hyperthermia combined with intravesical instillation of mitomycin C to reduce the risk of recurrence and progression of intermediate- and high-risk nonmuscle-invasive bladder cancer is currently investigated in clinical trials. Clinically effective locoregional hyperthermia delivery necessitates adequate thermal dosimetry; thus, optimal thermometry methods are needed to monitor accurately the temperature distribution throughout the bladder wall. The aim of the study was to evaluate the technical feasibility of a novel intravesical device (multi-sensor probe) developed to monitor the local bladder wall temperatures during loco-regional C-HT. Materials and Methods: A multisensor thermocouple probe was designed for deployment in the human bladder, using special sensors to cover the bladder wall in different directions. The deployment of the thermocouples against the bladder wall was evaluated with visual, endoscopic, and CT imaging in bladder phantoms, porcine models, and human bladders obtained from obduction for bladder volumes and different deployment sizes of the probe. Finally, porcine bladders were embedded in a phantom and subjected to locoregional heating to compare probe temperatures with additional thermometry inside and outside the bladder wall. Results: The 7.5 cm thermocouple probe yielded optimal bladder wall contact, adapting to different bladder volumes. Temperature monitoring was shown to be accurate and representative for the actual bladder wall temperature. Conclusions: Use of this novel multisensor probe could yield a more accurate monitoring of the bladder wall temperature during locoregional chemohyperthermia. PMID:24112045

  11. 17-DMAG induces heat shock protein 90 functional impairment in human bladder cancer cells: knocking down the hallmark traits of malignancy.

    Science.gov (United States)

    Karkoulis, Panagiotis K; Stravopodis, Dimitrios J; Voutsinas, Gerassimos E

    2016-05-01

    Heat shock protein 90 (Hsp90) is a molecular chaperone that maintains the structural and functional integrity of various protein clients involved in multiple oncogenic signaling pathways. Hsp90 holds a prominent role in tumorigenesis, as numerous members of its broad clientele are involved in the generation of the hallmark traits of cancer. 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) specifically targets Hsp90 and interferes with its function as a molecular chaperone, impairing its intrinsic ATPase activity and undermining proper folding of multiple protein clients. In this study, we have examined the effects of 17-DMAG on the regulation of Hsp90-dependent tumorigenic signaling pathways directly implicated in cell cycle progression, survival, and motility of human urinary bladder cancer cell lines. We have used MTT-based assays, FACS analysis, Western blotting, semiquantitative PCR (sqPCR), immunofluorescence, and scratch-wound assays in RT4 (p53(wt)), RT112 (p53(wt)), T24 (p53(mt)), and TCCSUP (p53(mt)) human urinary bladder cancer cell lines. We have demonstrated that, upon exposure to 17-DMAG, bladder cancer cells display prominent cell cycle arrest and commitment to apoptotic and autophagic cell death, in a dose-dependent manner. Furthermore, 17-DMAG administration induced pronounced downregulation of multiple Hsp90 protein clients and other downstream oncogenic effectors, therefore causing inhibition of cell proliferation and decline of cell motility due to the molecular "freezing" of critical cytoskeletal components. In toto, we have clearly demonstrated the dose-dependent and cell type-specific effects of 17-DMAG on the hallmark traits of cancer, appointing Hsp90 as a key molecular component in bladder cancer targeted therapy.

  12. Characterization of the early proliferative response of the rodent bladder to subtotal cystectomy: a unique model of mammalian organ regeneration.

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    Charles C Peyton

    Full Text Available Subtotal cystectomy (STC; surgical removal of ∼75% of the rat urinary bladder elicits a robust proliferative response resulting in complete structural and functional bladder regeneration within 8-weeks. The goal of these studies was to characterize the early cellular response that mediates this regenerative phenomenon, which is unique among mammalian organ systems. STC was performed on eighteen 12-week-old female Fischer F344 rats. At 1, 3, 5 and 7-days post-STC, the bladder was harvested 2-hours after intraperitoneal injection of bromodeoxyuridine (BrdU. Fluorescent BrdU labeling was quantified in cells within the urothelium, lamina propria (LP, muscularis propria (MP and serosa. Cell location was confirmed with fluorescently co-labeled cytokeratin, vimentin or smooth muscle actin (SMA, to identify urothelial, interstitial and smooth muscle cells, respectively. Expression of sonic hedgehog (Shh, Gli-1 and bone morphogenic factor-4 (BMP-4 were evaluated with immunochemistry. Three non-operated rats injected with BrdU served as controls. Less than 1% of cells in the bladder wall were labeled with BrdU in control bladders, but this percentage significantly increased by 5-8-fold at all time points post-STC. The spatiotemporal characteristics of the proliferative response were defined by a significantly higher percentage of BrdU-labeled cells within the urothelium at 1-day than in the MP and LP. A time-dependent shift at 3 and 5-days post-STC revealed significantly fewer BrdU-labeled cells in the MP than LP or urothelium. By 7-days the percentage of BrdU-labeled cells was similar among urothelium, LP and MP. STC also caused an increase in immunostaining for Shh, Gli-1 and BMP-4. In summary, the early stages of functional bladder regeneration are characterized by time-dependent changes in the location of the proliferating cell population, and expression of several evolutionarily conserved developmental signaling proteins. This report extends

  13. MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS

    Science.gov (United States)

    MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS Epidemiological studies have shown a positive association between chronic exposure to chlorinated drinking water and human cancer, particularly of the urinary bladder. MX (3- chloro-4-(dichloromethyl)-5-hydrox...

  14. Proteus mirabilis fimbriae- and urease-dependent clusters assemble in an extracellular niche to initiate bladder stone formation.

    Science.gov (United States)

    Schaffer, Jessica N; Norsworthy, Allison N; Sun, Tung-Tien; Pearson, Melanie M

    2016-04-19

    The catheter-associated uropathogenProteus mirabilisfrequently causes urinary stones, but little has been known about the initial stages of bladder colonization and stone formation. We found thatP. mirabilisrapidly invades the bladder urothelium, but generally fails to establish an intracellular niche. Instead, it forms extracellular clusters in the bladder lumen, which form foci of mineral deposition consistent with development of urinary stones. These clusters elicit a robust neutrophil response, and we present evidence of neutrophil extracellular trap generation during experimental urinary tract infection. We identified two virulence factors required for cluster development: urease, which is required for urolithiasis, and mannose-resistantProteus-like fimbriae. The extracellular cluster formation byP. mirabilisstands in direct contrast to uropathogenicEscherichia coli, which readily formed intracellular bacterial communities but not luminal clusters or urinary stones. We propose that extracellular clusters are a key mechanism ofP. mirabilissurvival and virulence in the bladder.

  15. Histologic alterations of the normal bladder wall following to variably fractionated irradiation - an experimentation on animals

    International Nuclear Information System (INIS)

    Fueller, J.; Fritzsche, V.; Kob, D.; Arndt, J.; Kriester, A.; Friedrich-Schiller-Universitaet, Jena

    1986-01-01

    The histopathologic alterations of the bladder wall were investigated in 180 rabbits irradiated with different fractionations and total focal doses. Animals sacrified one week after the end of irradiation showed alterations of the urothelium (desquamation, increased polymorphism of nuclei vacuolizations) as well as oedematous and hyperemic reactions in submucosa and muscularis. These alterations became stronger when the single and total focal dose and the ret values were increased. Animals sacrified three to six months after the end of irradiation showed dystrophic-sclerotic processes as well as vascular obliterations in the submucosa and muscularis. The alterations were only clearly visible in case of a total focal dose of at least 30 Gy. With regard to a minimization of histopathologic alterations of the bladder wall, a fractionation of 1.5 Gy per day has to be considered as favorable in radiotherapy of the carcinoma of the urinary bladder. (orig.) [de

  16. An analysis of suppressing migratory effect on human urinary bladder cancer cell line by silencing of snail-1.

    Science.gov (United States)

    Salehi, Shima; Mansoori, Behzad; Mohammadi, Ali; Davoudian, Sadaf; Musavi Shenas, Seyed Mohammad Hossein; Shajari, Neda; Majidi, Jafar; Baradaran, Behzad

    2017-12-01

    Snail-1 actively participates in tumor progression, invasion, and migration. Targeting snail-1 expression can suppress the EMT process in cancer. The aim of this study was to investigate the effect of snail1 silencing on urinary bladder cancer. Quantitative RT-PCR was used to detect snail-1 and other related metastatic genes expression following siRNA knockdown in urinary bladder cancer EJ-138 cells. The protein level of snail1 was assessed by Western blot. MTT and TUNEL assays were assessed to understand if snail-1 had survival effects on EJ-138 cells. Scratch wound healing assay measured cell motility effects after snail1 suppression. The significant silencing of snail-1 reached 60pmol siRNA in a 48-h post-transfection. The result of scratch assay showed that snail-1 silencing significantly decreased Vimentin, MMPs, and CXCR4 expression; however, expression of E-cadherin was induced. The cell death assay indicated that snail-1 played the crucial role in bladder cancer survival rate. These results propose that snail-1 plays a major role in the progression and migration of urinary bladder cancer, and can be a potential therapeutic target for target therapy of invasive urinary bladder cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. The influence of botulinum toxin type A (BTX) on the immunohistochemical characteristics of noradrenergic and cholinergic nerve fibers supplying the porcine urinary bladder wall.

    Science.gov (United States)

    Lepiarczyk, E; Bossowska, A; Kaleczyc, J; Majewski, M

    2011-01-01

    Botulinum toxin (BTX) belongs to a family of neurotoxins which strongly influence the function of autonomic neurons supplying the urinary bladder. Accordingly, BTX has been used as an effective drug in experimental therapies of a range of neurogenic bladder disorders. However, there is no detailed information dealing with the influence of BTX on the morphological and chemical properties of nerve fibres supplying the urinary bladder wall. Therefore, the present study investigated, using double-labeling immunohistochemistry, the distribution, relative frequency and chemical coding of cholinergic and noradrenergic nerve fibers supplying the wall of the urinary bladder in normal female pigs (n = 6) and in the pigs (n = 6) after intravesical BTX injections. In the pigs injected with BTX, the number of adrenergic (DbetaH-positive) nerve fibers distributed in the bladder wall (urothelium, submucosa and muscle coat) was distinctly higher while the number of cholinergic (VAChT-positive) nerve terminals was lower than that found in the control animals. Moreover, the injections of BTX resulted in some changes dealing with the chemical coding of the adrenergic nerve fibers. In contrast to the normal pigs, in BTX injected animals the number of DbetaH/NPY- or DbetaH/CGRP-positive axons was higher in the muscle coat, and some fibres distributed in the urothelium and submucosa expressed immunoreactivity to CGRP. The results obtained suggest that the therapeutic effects of BTX on the urinary bladder might be dependent on changes in the distribution and chemical coding of nerve fibers supplying this organ.

  18. [Neuroendocrine carcinoma of the urinary bladder. A case report].

    Science.gov (United States)

    Aragón-Tovar, Anel Rogelio; Pineda-Rodríguez, Marco Elí; Puente-Gallegos, Francisco Edgardo; Zavala-Pompa, Angel

    2014-01-01

    Small cell carcinoma of the urinary bladder is an infrequent lesion. We present the case of a 68-year-old male who arrived at the emergency room with a history of 24-h gross hematuria. Imaging studies show a urinary bladder tumor with a 218 cc volume that during a 20-day period increased to 426 cc. Histopathological images with hematoxylin-eosin show an infiltrating solid mass with uneven borders. It is composed of neoplastic cells with evident nuclei predominance and scant cytoplasm (small cells). Chromogranin immunohistochemical staining shows a diffusely positive cytoplasmic granular pattern on neoplastic cells. High molecular weight cytokeratin staining shows a negative pattern on neoplastic cells along with a positive pattern on reporsurrounding normal urothelium. Tumoral mass is positive for synaptophysin and CD-56 and negative for CK-7 and CK-20. Patient therapy was based on radiation plus chemotherapy. Small cell carcinoma of the urinary bladder represents 0.35-0.70% of urinary bladder tumors. Histological and immunohistochemical identification are key elements in the diagnosis. Treatment approach is based on cisplatin-based chemotherapy plus radical cystectomy, except when metastatic disease is present.

  19. Horseradish extract promotes urinary bladder carcinogenesis when administered to F344 rats in drinking water.

    Science.gov (United States)

    Cho, Young-Man; Hasumura, Mai; Imai, Toshio; Takami, Shigeaki; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2017-07-01

    Horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate and other isothiocyanates, has been used as a food additive. To evaluate the potential hazards of HRE, a 104-week chronic study, a 2-week analysis of cell proliferation in the urinary bladder and a medium-term promotion bioassay of HRE were conducted with administration at concentrations of up to 0.04% HRE in the drinking water to male F344 rats. In the 104-week chronic study with 32 male rats per group, no treatment-related increases in the incidences of neoplastic lesions in any organ, including urinary bladder, were observed, except for simple hyperplasia in the urinary bladder in rats treated with HRE at concentrations of more than 0.01% (5.0 mg kg -1 body weight day -1 ). In the promotion study, HRE treatment after N-butyl-N-(4-hydroxybutyl)nitrosamine initiation caused a clear increase in papillary or nodular hyperplasia, papilloma, and urothelial carcinoma of the urinary bladder in the groups given HRE for 13 weeks at doses higher than 0.005%, 0.01%, and 0.04% (2.7, 5.4 and 20.5 mg kg -1 body weight day -1 ), respectively. In the 2-week cell proliferation analysis, treatment with HRE at concentrations greater than 0.005% (3.9 mg kg -1 body weight day -1 ) caused transient increases in 5-bromo-2'-deoxyuridine labeling indices in the urothelium. Although clear tumor induction was not observed, administration of relatively low-dose HRE increased cell proliferation in the urothelium and exerted obvious promoting effects on rat urinary bladder carcinogenesis. Further studies are needed to elucidate the mode of action of HRE in the rat urinary bladder to facilitate data extrapolation from the present study and provide insights into risk assessment. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  20. The inflammatory and normal transcriptome of mouse bladder detrusor and mucosa

    Directory of Open Access Journals (Sweden)

    Dyer David W

    2006-01-01

    Full Text Available Abstract Background An organ such as the bladder consists of complex, interacting set of tissues and cells. Inflammation has been implicated in every major disease of the bladder, including cancer, interstitial cystitis, and infection. However, scanty is the information about individual detrusor and urothelium transcriptomes in response to inflammation. Here, we used suppression subtractive hybridizations (SSH to determine bladder tissue- and disease-specific genes and transcriptional regulatory elements (TREs. Unique TREs and genes were assembled into putative networks. Results It was found that the control bladder mucosa presented regulatory elements driving genes such as myosin light chain phosphatase and calponin 1 that influence the smooth muscle phenotype. In the control detrusor network the Pax-3 TRE was significantly over-represented. During development, the Pax-3 transcription factor (TF maintains progenitor cells in an undifferentiated state whereas, during inflammation, Pax-3 was suppressed and genes involved in neuronal development (synapsin I were up-regulated. Therefore, during inflammation, an increased maturation of neural progenitor cells in the muscle may underlie detrusor instability. NF-κB was specifically over-represented in the inflamed mucosa regulatory network. When the inflamed detrusor was compared to control, two major pathways were found, one encoding synapsin I, a neuron-specific phosphoprotein, and the other an important apoptotic protein, siva. In response to LPS-induced inflammation, the liver X receptor was over-represented in both mucosa and detrusor regulatory networks confirming a role for this nuclear receptor in LPS-induced gene expression. Conclusion A new approach for understanding bladder muscle-urothelium interaction was developed by assembling SSH, real time PCR, and TRE analysis results into regulatory networks. Interestingly, some of the TREs and their downstream transcripts originally involved in

  1. Long intergenic non-coding RNA TUG1 is overexpressed in urothelial carcinoma of the bladder.

    Science.gov (United States)

    Han, Yonghua; Liu, Yuchen; Gui, Yaoting; Cai, Zhiming

    2013-04-01

    Long intergenic non-coding RNAs (lincRNAs) are a class of non-coding RNAs that regulate gene expression via chromatin reprogramming. Taurine Up-regulated Gene 1 (TUG1) is a lincRNA that is associated with chromatin-modifying complexes and plays roles in gene regulation. In this study, we determined the expression patterns of TUG1 and the cell proliferation inhibition and apoptosis induced by silencing TUG1 in urothelial carcinoma of the bladder. The expression levels of TUG1 were determined using Real-Time qPCR in a total of 44 patients with bladder urothelial carcinomas. Bladder urothelial carcinoma T24 and 5637 cells were transfected with TUG1 siRNA or negative control siRNA. Cell proliferation was evaluated using MTT assay. Apoptosis was determined using ELISA assay. TUG1 was up-regulated in bladder urothelial carcinoma compared to paired normal urothelium. High TUG1 expression levels were associated with high grade and stage carcinomas. Cell proliferation inhibition and apoptosis induction were observed in TUG1 siRNA-transfected bladder urothelial carcinoma T24 and 5637 cells. Our data suggest that lincRNA TUG1 is emerging as a novel player in the disease state of bladder urothelial carcinoma. TUG1 may have potential roles as a biomarker and/or a therapeutic target in bladder urothelial carcinoma. Copyright © 2012 Wiley Periodicals, Inc.

  2. Apoptosis-related molecular differences for response to tyrosin kinase inhibitors in drug-sensitive and drug-resistant human bladder cancer cells

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    Jixia Li

    2013-01-01

    Full Text Available Context: The epidermal growth factor receptor (EGFR family is reportedly overexpressed in bladder cancer, and tyrosine kinaseinhibitors (TKIs have been suggested as treatment. Gefitinib is a selective inhibitor of the EGFR and lapatinib is a dual inhibitor of both the EGFR and HER2 (human EGFR type 2 receptor. Both compounds compete with the binding of adenosine triphosphate (ATP to the tyrosine kinase domain of the respective receptors to inhibit receptor autophosphorylation causing suppression of signal transduction. Unfortunately, resistance to these inhibitors is a major clinical problem. Aims: To compare the apoptosis signaling pathway(s induced by gefitinib and lapatinib, in UM-UC-5 (drug-sensitive and UM-UC-14 (drug-resistant bladder cancer cells and to identify molecular differences that might be useful predictors of their efficacy. Materials and Methods: Cell proliferation, cell cycle and apoptosis assay were used to detect the effect of TKIs on UM-UC-5 and UM-UC-14 cells. Molecular differences for response to TKIs were examined by protein array. Results: TKIs strongly inhibited cell proliferation and induced cell cycle G1 arrest and apoptosis in UM-UC-5 cells. Most notable apoptosis molecular differences included decreased claspin, trail, and survivin by TKIs in the sensitive cells. In contrast, TKIs had no effect on resistant cells. Conclusions: Claspin, trail, and survivin might be used to determine the sensitivity of bladder cancers to TKIs.

  3. The telocytes/myofibroblasts 3-D network forms a stretch receptor in the human bladder mucosa. Is this structure involved in the detrusor overactive diseases?

    Science.gov (United States)

    Vannucchi, Maria-Giuliana; Traini, Chiara

    2018-04-11

    Several connective tissue cells are present in the human bladder wall; among them, the myofibroblasts (MyF) and the so-called interstitial cells (IC) are a matter of investigation either by basic researchers or clinicians. The interest derives from the possibility that these two cell types could regulate the organ function forming a special sensory system in the bladder mucosa. Whereas attention for the myofibroblasts was mainly focused on understanding their role, the so-called IC are debatable starting from their nomenclature. Indeed, the IC should correspond to the previously called fibroblasts-like cells/interstitial Cajal-like cells (ICLC)/interstitial cells of Cajal (ICC) or PDGFRα positive cells, or CD34 positive cells. Recently a proper name was proposed to give them an identity, i.e. telocyte (TC). To date, this nomenclature is a better term than IC that is quite vague and can be used for all the cells that reside in the connective tissue. Noteworthy, in the bladder mucosa, TC and MyF form a hetero-cellular 3-D network. The detrusor overactivity/overactive bladder (DO/OAB) are pathological conditions characterized by hypersensitivity to filling. It has been hypothesized that erroneous afferent inputs generated in the mucosa affect the efferent pathways and, consequently, the detrusor response. Presently, we review the literature regarding the presence and the potential role of TC and MyF in control conditions and in DO/OAB. On the possibility that the 3D-network made up by these two cell types might play a major role in the genesis of anomalous afferent stimuli will be given attention. Copyright © 2018 Elsevier GmbH. All rights reserved.

  4. HAMLET treatment delays bladder cancer development.

    Science.gov (United States)

    Mossberg, Ann-Kristin; Hou, Yuchuan; Svensson, Majlis; Holmqvist, Bo; Svanborg, Catharina

    2010-04-01

    HAMLET is a protein-lipid complex that kills different types of cancer cells. Recently we observed a rapid reduction in human bladder cancer size after intravesical HAMLET treatment. In this study we evaluated the therapeutic effect of HAMLET in the mouse MB49 bladder carcinoma model. Bladder tumors were established by intravesical injection of MB49 cells into poly L-lysine treated bladders of C57BL/6 mice. Treatment groups received repeat intravesical HAMLET instillations and controls received alpha-lactalbumin or phosphate buffer. Effects of HAMLET on tumor size and putative apoptotic effects were analyzed in bladder tissue sections. Whole body imaging was used to study HAMLET distribution in tumor bearing mice compared to healthy bladder tissue. HAMLET caused a dose dependent decrease in MB49 cell viability in vitro. Five intravesical HAMLET instillations significantly decreased tumor size and delayed development in vivo compared to controls. TUNEL staining revealed selective apoptotic effects in tumor areas but not in adjacent healthy bladder tissue. On in vivo imaging Alexa-HAMLET was retained for more than 24 hours in the bladder of tumor bearing mice but not in tumor-free bladders or in tumor bearing mice that received Alexa-alpha-lactalbumin. Results show that HAMLET is active as a tumoricidal agent and suggest that topical HAMLET administration may delay bladder cancer development. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  5. Modulation of fibronectin-mediated Bacillus Calmette-Guérin attachment to murine bladder mucosa by drugs influencing the coagulation pathways.

    Science.gov (United States)

    Hudson, M A; Brown, E J; Ritchey, J K; Ratliff, T L

    1991-07-15

    Adjuvant intravesical Bacillus Calmette-Guérin (BCG) has proved to be an effective treatment for superficial bladder cancer. Intraluminal attachment of BCG organisms via binding to the extracellular matrix protein, fibronectin (FN), appears to be required for expression of the antitumor efficacy of BCG against a murine bladder tumor. Initial studies demonstrated that radiolabeled FN localized to the acutely injured urothelium but not to intact urothelium. These studies also demonstrated that exogenous administration of FN enhanced BCG attachment to the injured but not to the intact urothelium. Because FN has been shown to be an integral part of clot formation at sites of urothelial injury, drugs known to affect fibrin clot formation were tested for their effects on BCG attachment and antitumor efficacy in a murine bladder tumor model. A stabilizer of fibrin clot formation was shown to enhance both BCG attachment and antitumor efficacy in the same model. An increased number of BCG organisms were also retained in the lymph nodes and spleens of mice receiving fibrin clot stabilizers, suggesting indirectly that immunological mechanisms are involved in the antitumor efficacy of BCG. The data presented herein provide further support for the hypothesis that BCG attachment to the injured bladder is mediated by FN. Furthermore, modulation of BCG-FN attachment is demonstrated to be possible with drugs influencing the coagulation pathway. This attachment is shown to be required for the antitumor efficacy in a murine bladder tumor model, and thus modulation of BCG-FN attachment appears to have significant influence on the antitumor efficacy of BCG in the murine bladder tumor model.

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

    International Nuclear Information System (INIS)

    Qin Jie; Xie Liping; Zheng Xiangyi; Wang Yunbin; Bai Yu; Shen Huafeng; Li Longcheng; Dahiya, Rajvir

    2007-01-01

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

  7. Induction of glutathione S-transferase placental form positive foci in liver and epithelial hyperplasia in urinary bladder, but no tumor development in male Fischer 344 rats treated with monomethylarsonic acid for 104 weeks

    International Nuclear Information System (INIS)

    Shen Jun; Wanibuchi, Hideki; Salim, Elsayed I.; Wei Min; Doi, Kenichiro; Yoshida, Kaoru; Endo, Ginji; Morimura,; Fukushima, Shoji

    2003-01-01

    The carcinogenicity of monomethylarsonic acid (MMA(V)), a major metabolite of inorganic arsenics in human and experimental animals, was investigated in male Fischer 344 rats. A total of 129 rats at 10 weeks of age were randomly divided into three groups and received drinking water containing MMA(V) at doses of 0 (Control), 50, and 200 ppm ad libitum for 104 weeks. No significant differences were found between the control and the MMA(V)-treated groups regarding clinical signs, mortality, hematological, and serum biochemistry findings. Quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci in liver revealed a significant increase of numbers and areas in the 200 ppm MMA(V)-treated group. In the urinary bladder MMA(V) induced simple hyperplasia and significantly elevated the proliferating cell nuclear antigen (PCNA)-positive index in the urothelium. A variety of tumors developed in rats of all groups, including the controls, but all were histologically similar to those known to occur spontaneously in F344 rats and there were no significant differences among the groups. Thus, it could be concluded that, under the present experimental conditions, MMA(V) induced lesions in the liver and urinary bladder, but did not cause tumor development in male F344 rats even after 2 years exposure

  8. BCG-induced interleukin-6 upregulation and BCG internalization in well and poorly differentiated human bladder cancer cell lines

    NARCIS (Netherlands)

    Bevers, R. F.; de Boer, E. C.; Kurth, K. H.; Schamhart, D. H.

    1998-01-01

    Intravesical bacillus Calmette-Guerin (BCG) is a successful therapy for superficial bladder cancer. However, the working mechanism of BCG after intravesical instillation is not completely understood. A functional role of urothelial (tumor) cells in the initiation of the BCG-induced immune reaction

  9. A reactive oxygen species activation mechanism contributes to JS-K-induced apoptosis in human bladder cancer cells.

    Science.gov (United States)

    Qiu, Mingning; Chen, Lieqian; Tan, Guobin; Ke, Longzhi; Zhang, Sai; Chen, Hege; Liu, Jianjun

    2015-10-13

    Reactive oxygen species (ROS) and cellular oxidant stress are regulators of cancer cells. The alteration of redox status, which is induced by increased generation of ROS, results in increased vulnerability to oxidative stress. The aim of this study is to investigate the influence of O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, C13H16N6O8) on proliferation and apoptosis in bladder cancer cells and explored possible ROS-related mechanisms. Our results indicated that JS-K could suppress bladder cancer cell proliferation in a concentration- and time-dependent manner and induce apoptosis and ROS accumulation in a concentration-dependent manner. With increasing concentrations of JS-K, expression of proteins that are involved in cell apoptosis increased in a concentration-dependent manner. Additionally, the antioxidant N-acetylcysteine (NAC) reversed JS-K-induced cell apoptosis; conversely, the prooxidant oxidized glutathione (GSSG) exacerbated JS-K-induced cell apoptosis. Furthermore, we found that nitrites, which were generated from the oxidation of JS-K-released NO, induced apoptosis in bladder cancer cells to a lower extent through the ROS-related pathway. In addition, JS-K was shown to enhance the chemo-sensitivity of doxorubicin in bladder cancer cells. Taken together, the data suggest that JS-K-released NO induces bladder cancer cell apoptosis by increasing ROS levels, and nitrites resulting from oxidation of NO have a continuous apoptosis-inducing effect.

  10. Leiomyoma of urinary bladder with bladder stone

    International Nuclear Information System (INIS)

    Farouk, K.; Gondal, M.; Khan, A.

    2008-01-01

    Leiomyoma of the urinary bladder is a rare benign mesenchymal tumour. We describe here a case of leiomyoma of the urinary bladder in a 65-year-old gentleman who presented with haematuria, passage of clots and combined obstructive and irritative urinary symptoms. The investigations revealed a vesical calculus and a mass on the left lateral wall of the urinary bladder. Cystolitholapaxy and transurethral resection of the tumour was performed. Histopathological report of the resected tumour revealed a leiomyoma of the urinary bladder. So far, a leiomyoma of the urinary bladder and a concomitant vesical calculus have not been described in literature. (author)

  11. THE SIGNIFICANCE OF EPIDERMAL GROWTH FACTOR RECEPTOR AND SURVIVIN EXPRESSION IN BLADDER CANCER TISSUE AND URINE CYTOLOGY OF PATIENTS WITH TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER.

    Science.gov (United States)

    Kehinde, E O; Al-Maghrebi, M; Anim, J T; Kapila, K; George, S S; Al-Juwaiser, A; Memon, A

    2013-01-01

    To assess whether epidermal growth factor receptor (EGFR) and survivin immunostaining of tumour cells in urinary cytology and tissue of patients with bladder cancer has a prognostic significance. Prospective study Department of Surgery (Division of Urology), Mubarak Al-Kabeer Teaching Hospital and Faculty of Medicine, Kuwait University, Kuwait Urine cytology smears obtainedpriorto cystoscopy in patients with transitional cell carcinoma (TCC) of the bladder were immunostained for EGFR and survivin. Bladder cancer tissue resected at surgery was also immunostained for EGFR and survivin expression. Tissue expression of EGFR and survivin in TCC of the bladder was compared to their expression in urine cytology and relationship to tumour grade and stage. 178 patients were studied (43 newly diagnosed bladder cancer, 58 with recurrent TCC and 77 in disease remission). Twenty five patients with normal urothelium served as controls. The mean sensitivity of urine cytology, tissue survivin immunohistochemistry (IHC) and tissue EGFR IHC was 30.5%, 62% and 59% respectively. The corresponding mean specificity was 95%, 79% and 38% respectively. For grades 1, 2 and 3 bladder tumors, tissue expression positivity for EGFR was 47.8%, 92.9%, 100% and for tissue survivin it was 27.8%, 18.2% and 33.3% respectively. For grades 1, 2 and 3 bladder tumors, urine expression positivity for EGFR was 35.7%, 40% and 67.7% and for urine survivin it was 8.3%, 42.9% and 33.3% respectively. Positive EGFR immunostaining of urine cytology specimen or tumour tissue increases with histological grade of TCC of the bladder. Survivin expression is less consistent in both urine cytology specimen and tissue samples. EGFR immunostaining may provide a useful tool in the grading of bladder TCC and aid in the selection of patients that may benefit from administration of EGFR inhibitors.

  12. Effects of co-administration of dietary sodium arsenite and an NADPH oxidase inhibitor on the rat bladder epithelium

    International Nuclear Information System (INIS)

    Suzuki, Shugo; Arnold, Lora L.; Pennington, Karen L.; Kakiuchi-Kiyota, Satoko; Cohen, Samuel M.

    2009-01-01

    Arsenite (As III ), an inorganic arsenical, is a known human carcinogen, inducing tumors of the skin, urinary bladder and lung. It is metabolized to organic methylated arsenicals. Oxidative stress has been suggested as a mechanism for arsenic-induced carcinogenesis. Reactive oxygen species (ROS) can be important factors for carcinogenesis and tumor progression. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is known to produce intracellular ROS, therefore, we investigated the ability of apocynin (acetovanillone), an NADPH oxidase inhibitor, to inhibit the cytotoxicity and regenerative cell proliferation of arsenic in vitro and in vivo. Apocynin had similar effects in reducing the cytotoxicity of As III and dimethylarsinous acid (DMA III ) in rat urothelial cells in vitro. When tested at the same concentrations as apocynin, other antioxidants, such as L-ascorbate and N-acetylcysteine, did not inhibit As III -induced cytotoxicity but they were more effective at inhibiting DMA III -induced cytotoxicity compared with apocynin. In vivo, female rats were treated for 3 weeks with 100 ppm As III . Immunohistochemical staining for 8-hydroxy-2'-deoxyguanosine (8-OHdG) showed that apocynin reduced oxidative stress partially induced by As III treatment on rat urothelium, and significantly reduced the cytotoxicity of superficial cells detected by scanning electron microscopy (SEM). However, based on the incidence of simple hyperplasia and the bromodeoxyuridine (BrdU) labeling index, apocynin did not inhibit As III -induced urothelial cell proliferation. These data suggest that the NADPH oxidase inhibitor, apocynin, may have the ability to partially inhibit arsenic-induced oxidative stress and cytotoxicity of the rat bladder epithelium in vitro and in vivo. However, apocynin did not inhibit the regenerative cell proliferation induced by arsenite in a short-term study.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Evaluation of transforming growth factor-β1 suppress Pokemon/epithelial-mesenchymal transition expression in human bladder cancer cells.

    Science.gov (United States)

    Li, Wei; Kidiyoor, Amritha; Hu, Yangyang; Guo, Changcheng; Liu, Min; Yao, Xudong; Zhang, Yuanyuan; Peng, Bo; Zheng, Junhua

    2015-02-01

    Transforming growth factor-β1 (TGF-β1) plays a dual role in apoptosis and in proapoptotic responses in the support of survival in a variety of cells. The aim of this study was to determine the function of TGF-β1 in bladder cancer cells and the relationship with POK erythroid myeloid ontogenic factor (Pokemon). TGF-β1 and its receptors mediate several tumorigenic cascades that regulate cell proliferation, migration, and survival of bladder cancer cells. Bladder cancer cells T24 were treated with different levels of TGF-β1. Levels of Pokemon, E-cadherin, Snail, MMP2, MMP9, Twist, VEGF, and β-catenin messenger RNA (mRNA) and protein were examined by real-time quantitative fluorescent PCR and Western blot analysis, respectively. The effects of TGF-β1 on epithelial-mesenchymal transition of T24 cells were evaluated with wound-healing assay, proliferation of T24 was evaluated with reference to growth curves with MTT assay, and cell invasive ability was investigated by Transwell assay. Data show that Pokemon was inhibited by TGF-β1 treatment; the gene and protein of E-cadherin and β-catenin expression level showed decreased markedly after TGF-β1 treatment (P Pokemon, β-catenin, and E-cadherin. The high expression of TGF-β1 leads to an increase in the phenotype and apical-base polarity of epithelial cells. These changes of cells may result in the recurrence and progression of bladder cancer at last. Related mechanism is worthy of further investigation.

  15. Human epidermal growth factor receptor 2/neu overexpression in urothelial carcinoma of the bladder and its prognostic significance: Is it worth hype?

    Directory of Open Access Journals (Sweden)

    Santosh Kumar

    2015-01-01

    Full Text Available Aims: In urothelial tumors of the urinary bladder, human epidermal growth factor receptor 2 (HER-2/neu expression has been reported over 10 years, but there is no clear correlation between prognosis and recurrence rate. The present study evaluates prognostic implication of HER-2/neu expression. Subjects and Methods: In this study, 100 formalin-fixed paraffin-embedded specimens of primary transitional cell carcinoma of the bladder were processed. HER-2/neu monoclonal antibody immunohistochemistry staining procedure used for the study. Results: A total of 70 (70% patients were positive for overexpression of HER-2/neu. HER-2/neu was positive in patients with 42 (70% superficial tumor, 28 (70% muscle invasive tumor, 41 (75.9% high-grade tumor, 29 (63% low grade tumor, 31 (68.9% recurrent tumor, and 6 (66.6% had positive lymph nodes. Conclusions: Human epidermal growth factor receptor 2/neu over expression was not correlated with the tumor stage, lymphnode metastasis or recurrence of the disease. HER-2/neu overexpression was statistically insignificantly correlated with the differentiation grade (P < 0.161 as compared to previous studies. Future studies on HER-2 expression with chemo-sensitivity and efficacy of HER-2-targeted therapies in urothelial carcinomas is needed.

  16. The effect of radiation in combination with carcinogens on the growth of normal urothelium in explant culture

    International Nuclear Information System (INIS)

    Mothersill, C.; O'Brien, A.

    1990-01-01

    Radiation is known to be carcinogenic to humans but attempts to demonstrate the process using human tissue culture models have met with little success. In the present study explants were established from urothelium and exposed to radiation and a range of chemical carcinogens, suspected promotor or metabolic agents. The resulting outgrowth was monitored for growth rate, proliferating epithelial fraction and development and differentiation of endothelial cells in culture. The results indicate that enhanced growth of epithelial cells can be seen when cultures are irradiated in the presence of various nitrosamines, benzo(a)pyrene or aniline. Radiation alone reduced the overall growth area measured but several proliferative foci developed on the resulting outgrowth. Their ultrastructural appearance reveals that they carry severe mitochondrial damage and exposure of treated cultures to metabolic inhibitors confirms that their respiration is defective. Endothelial cells proliferated over the surface of the epithelial monolayer and both the number and the degree of differentiation of the endothelial cells increased with increasing dose up to 10 Gy. While the cultures are not immortalised by the treatment, it appears that the epithelial cells have an extended lifespan (division capacity) and that a subpopulation has undergone a number of premalignant changes. Changes in endothelial cell proliferation also occur. (orig.)

  17. Tissue engineering for human urethral reconstruction: systematic review of recent literature.

    Science.gov (United States)

    de Kemp, Vincent; de Graaf, Petra; Fledderus, Joost O; Ruud Bosch, J L H; de Kort, Laetitia M O

    2015-01-01

    Techniques to treat urethral stricture and hypospadias are restricted, as substitution of the unhealthy urethra with tissue from other origins (skin, bladder or buccal mucosa) has some limitations. Therefore, alternative sources of tissue for use in urethral reconstructions are considered, such as ex vivo engineered constructs. To review recent literature on tissue engineering for human urethral reconstruction. A search was made in the PubMed and Embase databases restricted to the last 25 years and the English language. A total of 45 articles were selected describing the use of tissue engineering in urethral reconstruction. The results are discussed in four groups: autologous cell cultures, matrices/scaffolds, cell-seeded scaffolds, and clinical results of urethral reconstructions using these materials. Different progenitor cells were used, isolated from either urine or adipose tissue, but slightly better results were obtained with in vitro expansion of urothelial cells from bladder washings, tissue biopsies from the bladder (urothelium) or the oral cavity (buccal mucosa). Compared with a synthetic scaffold, a biological scaffold has the advantage of bioactive extracellular matrix proteins on its surface. When applied clinically, a non-seeded matrix only seems suited for use as an onlay graft. When a tubularized substitution is the aim, a cell-seeded construct seems more beneficial. Considerable experience is available with tissue engineering of urethral tissue in vitro, produced with cells of different origin. Clinical and in vivo experiments show promising results.

  18. Cytokine expression in patients with bladder pain syndrome/interstitial cystitis ESSIC type 3C.

    Science.gov (United States)

    Logadottir, Yr; Delbro, Dick; Fall, Magnus; Gjertsson, Inger; Jirholt, Pernilla; Lindholm, Catharina; Peeker, Ralph

    2014-11-01

    Bladder wall nitric oxide production in patients with bladder pain syndrome type 3C is increased compared to undetectable nitric oxide in patients with nonHunner bladder pain syndrome and healthy controls. However, the underlying mechanism/s of the increased nitric oxide production is largely unknown. We compared mRNA expression of a select group of cytokines in patients with bladder pain syndrome/interstitial cystitis type 3C and in pain-free controls. Cold cup biopsies from 7 patients with bladder pain syndrome type 3C and 6 healthy subjects were analyzed. mRNA expression of IL-4, 6, 10 and 17A, iNOS, TNF-α, TGF-β and IFN-γ was estimated by real-time polymerase chain reaction. IL-17 protein expression was determined by immunohistochemistry. Mast cells were labeled with tryptase to evaluate cell appearance and count. IL-6, 10 and 17A, and iNOS mRNA levels as well as the number of mast cells infiltrating the bladder mucosa were significantly increased in patients with bladder pain syndrome type 3C compared to healthy controls. TNF-α, TGF-β and IFN-γ mRNA levels were similar in patients and controls. IL-17A expression at the protein level was up-regulated and localized to inflammatory cells and urothelium in patients with bladder pain syndrome type 3C. Patients with bladder pain syndrome/interstitial cystitis had increased mRNA levels of IL-17A, 10 and 6, and iNOS. IL-17A might be important in the inflammatory process. To our knowledge the increase in IL-17A is a novel finding that may have new treatment implications. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  19. A Non-Invasive Bladder Sensory Test Supports a Role for Dysmenorrhea Increasing Bladder Noxious Mechanosensitivity

    Science.gov (United States)

    TU, Frank F.; EPSTEIN, Aliza E.; POZOLO, Kristen E.; SEXTON, Debra L.; MELNYK, Alexandra I.; HELLMAN, Kevin M.

    2012-01-01

    Objective Catheterization to measure bladder sensitivity is aversive and hinders human participation in visceral sensory research. Therefore, we sought to characterize the reliability of sonographically-estimated female bladder sensory thresholds. To demonstrate this technique’s usefulness, we examined the effects of self-reported dysmenorrhea on bladder pain thresholds. Methods Bladder sensory threshold volumes were determined during provoked natural diuresis in 49 healthy women (mean age 24 ± 8) using three-dimensional ultrasound. Cystometric thresholds (Vfs – first sensation, Vfu – first urge, Vmt – maximum tolerance) were quantified and related to bladder urgency and pain. We estimated reliability (one-week retest and interrater). Self-reported menstrual pain was examined in relationship to bladder pain, urgency and volume thresholds. Results Average bladder sensory thresholds (mLs) were Vfs (160±100), Vfu (310±130), and Vmt (500±180). Interrater reliability ranged from 0.97–0.99. One-week retest reliability was Vmt = 0.76 (95% CI 0.64–0.88), Vfs = 0.62 (95% CI 0.44–0.80), and Vfu = 0.63, (95% CI 0.47–0.80). Bladder filling rate correlated with all thresholds (r = 0.53–0.64, p dysmenorrhea pain had increased bladder pain and urgency at Vfs and increased pain at Vfu (p’s dysmenorrhea pain was unrelated to bladder capacity. Discussion Sonographic estimates of bladder sensory thresholds were reproducible and reliable. In these healthy volunteers, dysmenorrhea was associated with increased bladder pain and urgency during filling but unrelated to capacity. Plausibly, dysmenorrhea sufferers may exhibit enhanced visceral mechanosensitivity, increasing their risk to develop chronic bladder pain syndromes. PMID:23370073

  20. Smooth Muscle-Like Cells Generated from Human Mesenchymal Stromal Cells Display Marker Gene Expression and Electrophysiological Competence Comparable to Bladder Smooth Muscle Cells.

    Directory of Open Access Journals (Sweden)

    Juliane Brun

    Full Text Available The use of mesenchymal stromal cells (MSCs differentiated toward a smooth muscle cell (SMC phenotype may provide an alternative for investigators interested in regenerating urinary tract organs such as the bladder where autologous smooth muscle cells cannot be used or are unavailable. In this study we measured the effects of good manufacturing practice (GMP-compliant expansion followed by myogenic differentiation of human MSCs on the expression of a range of contractile (from early to late myogenic markers in relation to the electrophysiological parameters to assess the functional role of the differentiated MSCs and found that differentiation of MSCs associated with electrophysiological competence comparable to bladder SMCs. Within 1-2 weeks of myogenic differentiation, differentiating MSCs significantly expressed alpha smooth muscle actin (αSMA; ACTA2, transgelin (TAGLN, calponin (CNN1, and smooth muscle myosin heavy chain (SM-MHC; MYH11 according to qRT-PCR and/or immunofluorescence and Western blot. Voltage-gated Na+ current levels also increased within the same time period following myogenic differentiation. In contrast to undifferentiated MSCs, differentiated MSCs and bladder SMCs exhibited elevated cytosolic Ca2+ transients in response to K+-induced depolarization and contracted in response to K+ indicating functional maturation of differentiated MSCs. Depolarization was suppressed by Cd2+, an inhibitor of voltage-gated Ca2+-channels. The expression of Na+-channels was pharmacologically identified as the Nav1.4 subtype, while the K+ and Ca2+ ion channels were identified by gene expression of KCNMA1, CACNA1C and CACNA1H which encode for the large conductance Ca2+-activated K+ channel BKCa channels, Cav1.2 L-type Ca2+ channels and Cav3.2 T-type Ca2+ channels, respectively. This protocol may be used to differentiate adult MSCs into smooth muscle-like cells with an intermediate-to-late SMC contractile phenotype exhibiting voltage-gated ion

  1. Smooth Muscle-Like Cells Generated from Human Mesenchymal Stromal Cells Display Marker Gene Expression and Electrophysiological Competence Comparable to Bladder Smooth Muscle Cells.

    Science.gov (United States)

    Brun, Juliane; Lutz, Katrin A; Neumayer, Katharina M H; Klein, Gerd; Seeger, Tanja; Uynuk-Ool, Tatiana; Wörgötter, Katharina; Schmid, Sandra; Kraushaar, Udo; Guenther, Elke; Rolauffs, Bernd; Aicher, Wilhelm K; Hart, Melanie L

    2015-01-01

    The use of mesenchymal stromal cells (MSCs) differentiated toward a smooth muscle cell (SMC) phenotype may provide an alternative for investigators interested in regenerating urinary tract organs such as the bladder where autologous smooth muscle cells cannot be used or are unavailable. In this study we measured the effects of good manufacturing practice (GMP)-compliant expansion followed by myogenic differentiation of human MSCs on the expression of a range of contractile (from early to late) myogenic markers in relation to the electrophysiological parameters to assess the functional role of the differentiated MSCs and found that differentiation of MSCs associated with electrophysiological competence comparable to bladder SMCs. Within 1-2 weeks of myogenic differentiation, differentiating MSCs significantly expressed alpha smooth muscle actin (αSMA; ACTA2), transgelin (TAGLN), calponin (CNN1), and smooth muscle myosin heavy chain (SM-MHC; MYH11) according to qRT-PCR and/or immunofluorescence and Western blot. Voltage-gated Na+ current levels also increased within the same time period following myogenic differentiation. In contrast to undifferentiated MSCs, differentiated MSCs and bladder SMCs exhibited elevated cytosolic Ca2+ transients in response to K+-induced depolarization and contracted in response to K+ indicating functional maturation of differentiated MSCs. Depolarization was suppressed by Cd2+, an inhibitor of voltage-gated Ca2+-channels. The expression of Na+-channels was pharmacologically identified as the Nav1.4 subtype, while the K+ and Ca2+ ion channels were identified by gene expression of KCNMA1, CACNA1C and CACNA1H which encode for the large conductance Ca2+-activated K+ channel BKCa channels, Cav1.2 L-type Ca2+ channels and Cav3.2 T-type Ca2+ channels, respectively. This protocol may be used to differentiate adult MSCs into smooth muscle-like cells with an intermediate-to-late SMC contractile phenotype exhibiting voltage-gated ion channel

  2. Epithelial mesenchymal transition status is associated with anti-cancer responses towards receptor tyrosine-kinase inhibition by dovitinib in human bladder cancer cells

    International Nuclear Information System (INIS)

    Hänze, Jörg; Henrici, Marcus; Hegele, Axel; Hofmann, Rainer; Olbert, Peter J

    2013-01-01

    Dovitinib (TKI-258) is a receptor tyrosine kinase (RTK) inhibitor targeting fibroblast growth factor receptor (FGFR) and further related RTKs. TKI-258 is under investigation as anticancer drug for the treatment of various cancers including bladder cancer with aberrant RTK signaling. Here, we analyzed the responses of ten human bladder cancer cell lines towards TKI-258 treatment in relation to the epithelial mesenchymal transition (EMT) status of the cells. Expression of epithelial marker E-cadherin as well as mesenchymal markers N-cadherin and vimentin was determined by quantitative RT-PCR and Western-blot in RNA and protein extracts from the cultured cell lines. The cell responses were analyzed upon addition of TKI-258 by viability/proliferation (XTT assay) and colony formation assay for measurement of cell contact independent growth. The investigated bladder cancer cell lines turned out to display quite different EMT patterns as indicated by the abundance of E-cadherin or N-cadherin and vimentin. Protein and mRNA levels of the respective components strongly correlated. Based on E-cadherin and N-cadherin mRNA levels that were expressed approximately mutual exclusively, an EMT-score was calculated for each cell line. A high EMT-score indicated mesenchymal-like cells and a low EMT-score epithelial-like cells. Then, we determined the IC 50 values for TKI-258 by dose response curves (0-12 μM TKI-258) in XTT assays for each cell line. Also, we measured the clonogenic survival fraction after adding TKI-258 (1 μM) by colony formation assay. We observed significant correlations between EMT-score and IC 50 values (r = 0.637, p = 0.0474) and between EMT-score and clonogenic survival fraction (r = 0.635, p = 0.0483) as analyzed by linear regression analyses. In sum, we demonstrated that the EMT status based on E-cadherin and N-cadherin mRNA levels may be useful to predict responses towards TKI-258 treatment in bladder cancer

  3. Bladder sensation measures and overactive bladder.

    Science.gov (United States)

    Rapp, David E; Neil, Nancy J; Govier, Fred E; Kobashi, Kathleen C

    2009-09-01

    We performed a prospective multicomponent study to determine whether subjective and objective bladder sensation instruments may provide data on sensory dysfunction in patients with overactive bladder. We evaluated 70 prospectively enrolled patients with urodynamics and questionnaires on validated urgency (Urgency Perception Score), general overactive bladder (Urogenital Distress Inventory) and quality of life (Incontinence Impact Questionnaire). We first sought a correlation between sensory specific (Urgency Perception Score) and quality of life questionnaire scores. We then assessed a correlation between sensory questionnaire scores and urodynamic variables, exploring the hypothesis that certain urodynamic parameters may be bladder sensation measures. We evaluated 2 urodynamic derivatives (first sensation ratio and bladder urgency velocity) to increase sensory finding discrimination. We noted a moderate correlation between the Urgency Perception Score (0.56) and the Urogenital Distress Inventory (0.74) vs the Incontinence Impact Questionnaire (each p Perception Score and bladder capacity (-0.25, p sensation ratio and bladder urgency velocity statistically significantly correlated with the Urgency Perception Score despite the lesser or absent correlation associated with the individual components of these derivatives. Bladder sensation questionnaires may be valuable to identify patients with sensory dysfunction and provide additional data not obtained in generalized symptom questionnaires. Urodynamic variables correlated with bladder sensation questionnaire scores and may be an objective method to assess sensory dysfunction.

  4. New approaches to obtaining scientific innovation in morphological studies of bladder transitional epithelium

    Directory of Open Access Journals (Sweden)

    O Popadynets

    2017-06-01

    Full Text Available Objective: To demonstrate the capabilities of cluster analysis in receiving scientific innovation results in morphological studies of cells of the bladder urothelium. Materials and methods.10 Wistar rats were used. Histological sections were stained with hematoxylin and eosin; electron microscope studies were  conducted; morphometry was performed in ImageJ and statistics – in studio-R using nonparametric methods and multivariate statistics. Results. A brief description of the main stages of cluster analysis shows way to determine the most important features of uroteliocytes and to reveal their heterogeneity, algorithms of Euclidean metrics and methods of clustering were described, the features of the application of the analysis in morphological studies were presented, an example of using these methods in searching for new results was presented, the models of morphological substantiation of clustering results were showed.  Conclusion: 1 cluster analysis provides a scientific novelty in studies of transitional epithelium of the bladder; 2 it is used in case of heterogeneity of cellular composition of urothelium that is detected with a help of coefficient of variation; 3 the most significant features of uroteliocytes are their cell area and their nuclei area; 4 new results on the number of clusters were obtained by method of Ward, and new data on their indicators – by k-means; 5 Euclidean metric is the best to use; 6 to assess the adequacy of the results pairwise comparisons between multiple clusters were carried out according to their indicators; 7 results are presented in dimentional projection and they characterize cellular composition of the urothelium as structural system and detect systemic effects.

  5. Androgen receptor signals regulate UDP-glucuronosyltransferases in the urinary bladder: a potential mechanism of androgen-induced bladder carcinogenesis.

    Science.gov (United States)

    Izumi, Koji; Zheng, Yichun; Hsu, Jong-Wei; Chang, Chawnshang; Miyamoto, Hiroshi

    2013-02-01

    UDP-glucuronosyltransferases (UGTs), major phase II drug metabolism enzymes, play an important role in urinary bladder cancer initiation by detoxifying carcinogens. We aimed to determine if androgens regulate UGT expression via the androgen receptor (AR) pathway in the bladder. Real-time reverse transcription-polymerase chain reaction and Western blot analyses were used to assess UGT1A levels in the normal urothelium SVHUC cell line stably expressed with AR and in bladder tissues from AR knockout (ARKO) and castrated male mice. Immunohistochemistry was also performed in radical cystectomy specimens. Dihydrotestosterone (DHT) treatment in SVHUC-AR reduced mRNA expression of all the UGT1A subtypes (19-75% decrease), and hydroxyflutamide antagonized the DHT effects. In contrast, DHT showed only marginal effects on UGT1A expression in SVHUC-Vector. Of note were higher expression levels of UGT1As in SVHUC-Vector than in SVHUC-AR. In ARKO mice, all the Ugt1a subtypes were up-regulated, compared to wild-type littermates. In wild-type male mice, castration increased the expression of Ugt1a8, Ugt1a9, and Ugt1a10. Additionally, wild-type female mice had higher levels of Ugt1a than wild-type males. Immunohistochemical studies showed strong (3+) UGT1A staining in 11/24 (46%) cancer tissues, which was significantly lower than in corresponding benign tissues [17/18 (94%) cases (P = 0.0009)]. These results suggest that androgen-mediated AR signals promote bladder carcinogenesis by down-regulating the expression of UGTs in the bladder. Copyright © 2011 Wiley Periodicals, Inc.

  6. Morphological examination of the effects of defibrotide on experimentally induced bladder injury and its relation to interstitial cystitis.

    Science.gov (United States)

    Aydin, H; Ercan, F; Cetinel, S; San, T

    2001-08-01

    This morphological study aims to investigate the effects of defibrotide, a deoxyribonucleic acid derivative drug with cytoprotective, immunosuppressive and vasorelaxant effects, on protamine sulfate induced bladder injury. Wistar albino female rats were catheterized and intravesically infused with phosphate buffered solution (control group) or, either protamine sulfate (bladder injury group) or protamine sulfate+defibrotide (bladder injury+defibrotide group) dissolved in phosphate buffered solution. The morphology of the urinary bladder was investigated using light and electron microscopy. The number of mast cells in the mucosa, mucosal alterations, intercellular junctions, surface topography and the glycosaminoglycan (GAG) layer as well as microvillus formation on the luminal surface were evaluated. In the bladder injury group, ulcerated areas, irregularity of the GAG layer, increased number of mast cells, vacuole formation, dilated perinuclear cistern, formation of pleomorphic and uniform microvilli and dilatations in the intercellular spaces in the urothelium were observed. In the bladder injury+defibrotide group a relatively normal urothelial topography, GAG layer and a few mast cells in the mucosa, some dilatations between the intercellular areas, less uniform microvilli, regular perinuclear cistern and tight junctions were observed. These results show that defibrotide can inhibit PS induced bladder damage.

  7. Vinflunine in the treatment of bladder cancer

    Directory of Open Access Journals (Sweden)

    Mark Bachner

    2008-11-01

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

  8. The paediatric neuropathic bladder

    African Journals Online (AJOL)

    pathophysiological terms, a neurogenic bladder is caused by a spinal reflex arc that occurs when ... and potential progressive renal damage because of high bladder ... creatinine level, can also be used to assess kidney function. Urodynamic ...

  9. Omega-3 Fatty Acids Inhibit Tumor Growth in a Rat Model of Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Belmiro Parada

    2013-01-01

    Full Text Available Omega-3 (ω-3 fatty acids have been tested on prevention and treatment of several cancer types, but the efficacy on “in vivo” bladder cancer has not been analyzed yet. This study aimed at evaluating the chemopreventive efficacy of eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA mixture in an animal model of bladder cancer. Forty-four male Wistar rats were divided into 4 groups during a 20-week protocol: control; carcinogen—N-butyl-N-(4-hydroxybutyl nitrosamine (BBN; ω-3 (DHA + EPA; and ω-3 + BBN. BBN and ω-3 were given during the initial 8 weeks. At week 20 blood and bladder were collected and checked for the presence of urothelium lesions and tumors, markers of inflammation, proliferation, and redox status. Incidence of bladder carcinoma was, control (0%, ω-3 (0%, BBN (65%, and ω-3 + BBN (62.5%. The ω-3 + BBN group had no infiltrative tumors or carcinoma in situ, and tumor volume was significantly reduced compared to the BBN (0.9 ± 0.1 mm3 versus 112.5 ± 6.4 mm3. Also, it showed a reduced MDA/TAS ratio and BBN-induced serum CRP, TGF-β1, and CD31 were prevented. In conclusion, omega-3 fatty acids inhibit the development of premalignant and malignant lesions in a rat model of bladder cancer, which might be due to anti-inflammatory, antioxidant, anti-proliferative, and anti-angiogenic properties.

  10. Pattern of somatostatin receptors expression in normal and bladder cancer tissue samples.

    Science.gov (United States)

    Karavitakis, Markos; Msaouel, Pavlos; Michalopoulos, Vassilis; Koutsilieris, Michael

    2014-06-01

    Known risks factors for bladder cancer progression and recurrence are limited regarding their prognostic ability. Therefore identification of molecular determinants of disease progression could provide with more specific prognostic information and could be translated into new approaches for biomarker development. In the present study we evaluated, the expression patterns of somatostatin receptors 1-5 (SSTRs) in normal and tumor bladder tissues. The expression of SSTR1-5 was characterized in 45 normal and bladder cancer tissue samples using reverse transcriptase-polymerase chain reaction (RT-PCR). SSTR1 was expressed in 24 samples, SSTR2 in 15, SSTR3 in 23, SSTR4 in 16 and SSTR5 in all but one sample. Bladder cancer tissue samples expressed lower levels of SSTR3. Co-expression of SSTRs was associated with superficial disease. Our results demonstrate, for the first time, that there is expression of SSTR in normal and bladder cancer urothelium. Further studies are required to evaluate the prognostic and therapeutic significance of these findings. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  11. Diuron-induced rat urinary bladder carcinogenesis: mode of action and human relevance evaluations using the International Programme on Chemical Safety framework.

    Science.gov (United States)

    Da Rocha, Mitscheli Sanches; Arnold, Lora L; De Oliveira, Maria Luiza Cotrim Sartor; Catalano, Shadia M Ihlaseh; Cardoso, Ana Paula Ferragut; Pontes, Merielen G N; Ferrucio, Bianca; Dodmane, Puttappa R; Cohen, Samuel M; De Camargo, João Lauro V

    2014-05-01

    Diuron, a high volume substituted urea herbicide, induced high incidences of urinary bladder carcinomas and low incidences of kidney pelvis papillomas and carcinomas in rats exposed to high doses (2500 ppm) in a 2-year bioassay. Diuron is registered for both occupational and residential uses and is used worldwide for more than 30 different crops. The proposed rat urothelial mode of action (MOA) for this herbicide consists of metabolic activation to metabolites that are excreted and concentrated in the urine, leading to cytotoxicity, urothelial cell necrosis and exfoliation, regenerative hyperplasia, and eventually tumors. We show evidence for this MOA for diuron using the International Programme on Chemical Safety (IPCS) conceptual framework for evaluating an MOA for chemical carcinogens, and the United States Environmental Protection Agency (USEPA) and IPCS framework for assessing human relevance.

  12. The effect of TGF-beta2 on MMP-2 production and activity in highly metastatic human bladder carcinoma cell line 5637.

    Science.gov (United States)

    Dehnavi, Ehsan; Soheili, Zahra-Soheila; Samiei, Shahram; Ataei, Zahra; Aryan, Hajar

    2009-06-01

    Transforming growth factor-beta (TGF-beta) superfamily regulates matrix metalloproteinases (MMP), which intrinsically regulate various cell behaviors leading to metastasis. We investigated the effect of TGF-beta(2) on MMP-2 regulation in human bladder carcinoma cell line 5637. Zymography, ELISA, and real-time polymerase chain reaction revealed that TGF-beta(2) stimulated MMP-2 production, but the transcription of its gene remained unchanged. Wortmannin could not inhibit MMP-2 secretion and activity and conversely the amount of the protein and its enzymatic activity were increased. These data suggest that TGF-beta(2) increased MMP-2 at the posttranscriptional level and this upregulation was independent of phosphatidylinositol 3-kinase signaling pathway.

  13. 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.

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

    Science.gov (United States)

    Fulkerson, Christopher M; Dhawan, Deepika; Ratliff, Timothy L; Hahn, Noah M; Knapp, Deborah W

    2017-01-01

    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.

  15. Overexpression of HER-2 via immunohistochemistry in canine urinary bladder transitional cell carcinoma - A marker of malignancy and possible therapeutic target.

    Science.gov (United States)

    Millanta, F; Impellizeri, J; McSherry, L; Rocchigiani, G; Aurisicchio, L; Lubas, G

    2018-06-01

    Transitional cell carcinoma (TCC) is the most commonly diagnosed neoplasm in the urinary bladder. Distant metastases to the regional lymph nodes, lungs, abdominal organs or bones are noted in up to 50% of dogs at time of death. Surgical excision is often not practical as TCC typically involve the trigone of the bladder and/or occurs multifocally throughout the bladder with field cancerization. Therapeutic approaches are very challenging and the requirement to evaluate alternative therapeutic protocols that may prolong survival times in dogs bearing these tumours is compelling. We assessed the immunohistochemical expression of HER-2 in 23 cases of canine TCCs of the urinary bladder and compare it with non-neoplastic urothelium in order to evaluate a rationale for targeted therapies and gene-based vaccines. HER-2 positivity was recorded in 13/23 (56%) neoplastic lesions. The receptor was significantly overexpressed in neoplastic than in non-neoplastic samples (P = .015). According to our preliminary results, it would be of interest to further evaluate the role of HER-2 in canine TCCs as a marker of malignancy and a therapeutic target for cancer vaccine and antibodies. Moreover, the significantly different overexpression of HER-2 in TCCs than in non-neoplastic urothelium further supports to investigate its role in the progression toward malignancy of non-neoplastic lesions. © 2017 John Wiley & Sons Ltd.

  16. Thrombomodulin expression regulates tumorigenesis in bladder cancer

    International Nuclear Information System (INIS)

    Wu, Chun-Te; Chang, Ying-Hsu; Lin, Paul- Yang; Chen, Wen-Cheng; Chen, Miao-Fen

    2014-01-01

    The identification of potential tumor markers will help improve therapeutic planning and patient management. Thrombomodulin (TM) is a sensitive urothelial marker. TM was reported to be one of the endogenous anti-metastatic factors and has diagnostic and prognostic values for the progression of carcinoma. In the present study, we examine the role of TM in bladder cancer. We studied the role of TM in tumor behavior and related signaling pathways in vitro using the human bladder cancer cell lines HT1376, HT1197, J82 and T24, and in vivo using animal models. We also selected clinical specimens from 100 patients with bladder cancer for immunohistochemical staining to evaluate the predictive capacity of TM in tumor invasiveness. The data revealed that positive immunoreactivity for TM was inversely correlated with clinical stage and DNA methyltransferase 1 immunoreactivity. Decreased TM expression could predict the aggressive tumor growth and advanced clinical stage in bladder cancer. When TM was inhibited, tumor growth rate and invasion ability were augmented in vitro and in vivo. The underlying changes included increased cell proliferation, enhanced epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, inhibition of NF-κB activation significantly increased TM expression and attenuated tumor aggressiveness in bladder cancer. TM plays an important role in bladder cancer tumor aggressiveness in vitro and in vivo and is a clinically significant predictor that may represent a suitable therapeutic target for bladder cancer

  17. Regulation of ACh release from guinea pig bladder urothelial cells: potential role in bladder filling sensations.

    Science.gov (United States)

    McLatchie, L M; Young, J S; Fry, C H

    2014-07-01

    The aim of this study was to quantify and characterize the mechanism of non-neuronal ACh release from bladder urothelial cells and to determine if urothelial cells could be a site of action of anti-muscarinic drugs. A novel technique was developed whereby ACh could be measured from freshly isolated guinea pig urothelial cells in suspension following mechanical stimulation. Various agents were used to manipulate possible ACh release pathways in turn and to study the effects of muscarinic receptor activation and inhibition on urothelial ATP release. Minimal mechanical stimulus achieved full ACh release, indicating a small dynamic range and possible all-or-none signal. ACh release involved a mechanism dependent on the anion channel CFTR and intracellular calcium concentration, but was independent of extracellular calcium, vesicular trafficking, connexins or pannexins, organic cation transporters and was not affected by botulinum-A toxin. Stimulating ACh receptors increased ATP production and antagonizing them reduced ATP release, suggesting a link between ACh and ATP release. These results suggest that release of non-neuronal ACh from the urothelium is large enough and well located to act as a modulator of ATP release. It is hypothesized that this pathway may contribute to the actions of anti-muscarinic drugs in reducing the symptoms of lower urinary tract syndromes. Additionally the involvement of CFTR in ACh release suggests an exciting new direction for the treatment of these conditions. © 2014 The British Pharmacological Society.

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

    International Nuclear Information System (INIS)

    Li, Kuiqing; Chen, Xu; Liu, Cheng; Gu, Peng; Li, Zhuohang; Wu, Shaoxu; Xu, Kewei; Lin, Tianxin; Huang, Jian

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-01

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

  20. A Novel Role of Dickkopf-Related Protein 3 in Macropinocytosis in Human Bladder Cancer T24 Cells

    Directory of Open Access Journals (Sweden)

    Nonoka Tsujimura

    2016-11-01

    Full Text Available Dickkopf-related protein 3 (Dkk-3 is a potential tumor suppressor reported in various cancer entities. However, we found that Dkk-3 was exceptionally upregulated in bladder cancer T24 cells. To validate the biological role of Dkk-3 other than a tumor suppressor, we examined the function of Dkk-3 in T24 cells. Gene silencing of Dkk-3 inhibited cell growth through inducing G0/G1 cell-cycle arrest. Furthermore, Dkk-3 knock-down caused macropinocytosis accompanied by autophagy, which were canceled in part by their inhibitors 5-(N-ethyl-N-isopropyl amiloride (EIPA and 3-methyladenine (3-MA. The macropinocytosis was induced by the Dkk-3 knock-down when there were sufficient extracellular nutrients. On the other hand, when the nutritional condition was poor, the autophagy was mainly induced by the Dkk-3 knock-down. These data indicated that Dkk-3 has a role in modulating macropinocytotic and autophagic pathways, a distinct function other than a Wnt antagonist.

  1. A Novel Role of Dickkopf-Related Protein 3 in Macropinocytosis in Human Bladder Cancer T24 Cells

    Science.gov (United States)

    Tsujimura, Nonoka; Yamada, Nami O.; Kuranaga, Yuki; Kumazaki, Minami; Shinohara, Haruka; Taniguchi, Kohei; Akao, Yukihiro

    2016-01-01

    Dickkopf-related protein 3 (Dkk-3) is a potential tumor suppressor reported in various cancer entities. However, we found that Dkk-3 was exceptionally upregulated in bladder cancer T24 cells. To validate the biological role of Dkk-3 other than a tumor suppressor, we examined the function of Dkk-3 in T24 cells. Gene silencing of Dkk-3 inhibited cell growth through inducing G0/G1 cell-cycle arrest. Furthermore, Dkk-3 knock-down caused macropinocytosis accompanied by autophagy, which were canceled in part by their inhibitors 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and 3-methyladenine (3-MA). The macropinocytosis was induced by the Dkk-3 knock-down when there were sufficient extracellular nutrients. On the other hand, when the nutritional condition was poor, the autophagy was mainly induced by the Dkk-3 knock-down. These data indicated that Dkk-3 has a role in modulating macropinocytotic and autophagic pathways, a distinct function other than a Wnt antagonist. PMID:27827955

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

    Science.gov (United States)

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

    2011-02-01

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

  3. The recovery of bladder epithelial hyperplasia caused by a melamine diet-induced bladder calculus in mice.

    Science.gov (United States)

    Sun, Ying; Jiang, Yi-Na; Xu, Chang-Fu; Du, Yun-Xia; Zhang, Jiao-Jiao; Yan, Yang; Gao, Xiao-Li

    2014-02-01

    Applying a model of bladder epithelial hyperplasia (BEH) caused by melamine-induced bladder calculus (BC), the recovery of BEH after melamine withdrawal was investigated. One experiment, comprising untreated, melamine and recovery groups, was conducted in Balb/c mice. Each group included 4 subgroups. Mice were fed normal-diet in untreated or a melamine-diet in other groups. The melamine-diet was then substituted with normal-diet in recovery group. Both of BC and BEH were observed after 14 and 56 days of melamine-diet. The BC is relatively uniform at the same melamine-diet durations. The BEH was diffuse with many mitotic figures, 4-7 rows of nuclei, and well-defined umbrella/intermediate cells. No marked differences in BEH degree were observed in the two different melamine-diet durations. On 4-42 days after melamine withdrawal, BC was not found, as the progressive regression with complete regression of BEH was observed, along with well-defined ageing/apoptotic cells in the superficial regions of BEH regression tissue. Conclusion, the melamine-induced BEH is relatively uniform, may be self-limiting in rows of nuclei, and can return to normal. Melamine withdrawal duration is critical for the BEH regression. Tissue of the BEH and its regression is ideal for exploring the renewal as well as growth biology of mammalian urothelium. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  4. 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....

  5. Variation in the binding of 125I-labeled interferon-beta ser to cellular receptors during growth of human renal and bladder carcinoma cells in vitro

    International Nuclear Information System (INIS)

    Ruzicka, F.J.; Schmid, S.M.; Groveman, D.S.; Cummings, K.B.; Borden, E.C.

    1987-01-01

    Studies of various established human bladder and renal carcinoma cell lines cultured in vitro demonstrated the presence of specific, saturable, high affinity binding sites for 125 I-labeled human interferon Beta ser IFN-beta ser). This recombinant produced interferon labeled with approximately one atom of 125 I/molecule of IFN expressed minimal or no loss of antiviral activity. A single class of binding sites (1000-2000/cell) with an affinity constant of 10(10)-10(11) L/M was measured at 4 degrees C for cells exhibiting widely different sensitivity to the antiproliferative effect of IFN-beta ser. Major fluctuations in the binding of 125 I-labeled IFN-beta ser to cellular receptors were observed during in vitro proliferation of four of five cell lines examined. A significant decrease (P less than 0.001) in specific binding was observed 48 h after cultures were established. Cell cycle analysis suggested that within the first 24 h and in the very late log and stationary phase of growth of ACHN (human renal carcinoma) cells, variations in the binding of 125 I-labeled IFN-beta ser were partially attributable to binding fluctuations during the mitotic cycle. The 2- to 3-fold decline 24 h following plating of ACHN cells corresponded to a 70% decrease in the number of cells in G0-G1. T24 (human transitional cell carcinoma) and ACHN cells, synchronized by serum starvation, demonstrated increased binding of 125 I-labeled IFN-beta ser 4-16 h following serum replenishment. This increase in receptor binding occurred prior to the onset of DNA and protein synthesis and was followed by a decline immediately prior to cell division. Binding site analysis indicated that the increased binding prior to DNA synthesis was due to a 5- to 6-fold increase in receptor affinity for the radiolabeled ligand

  6. Bladder necrosis: 'A man without a bladder'.

    Science.gov (United States)

    Bosschieter, Judith; Oudshoorn, Frederik H K; Meuleman, Eric J H; Nieuwenhuijzen, Jakko A

    2018-02-17

    Since the use of antibiotics, bladder necrosis has become a rare condition. We report a case of bladder necrosis in a 90-year-old man following urinary retention. After insertion of a transurethral catheter (TUC), 2 L of urine was evacuated. In the following days, the TUC became intermittently blocked. Adequate bladder drainage could not be obtained despite intensive rinsing and placement of a suprapubic catheter. On surgical exploration necrosis of almost the entire bladder wall, except for the trigone, was encountered. Surgical debridement of the non-viable bladder wall without opening the abdominal cavity was conducted, and a TUC was placed in the Retzius cavity to ensure evacuation of urine. Since the patient was haemodynamically unstable, construction of a urinary diversion was waived and urinary drainage of the Retzius cavity by the TUC was accepted, resulting in adequate urinary drainage without compromising renal function. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Gender and Bladder Cancer: A Collaborative Review of Etiology, Biology, and Outcomes.

    Science.gov (United States)

    Dobruch, Jakub; Daneshmand, Siamak; Fisch, Margit; Lotan, Yair; Noon, Aidan P; Resnick, Matthew J; Shariat, Shahrokh F; Zlotta, Alexandre R; Boorjian, Stephen A

    2016-02-01

    The incidence of bladder cancer is three to four times greater in men than in women. However, women are diagnosed with more advanced disease at presentation and have less favorable outcomes after treatment. To review the literature on potential biologic mechanisms underlying differential gender risk for bladder cancer, and evidence regarding gender disparities in bladder cancer presentation, management, and outcomes. A literature search of English-language publications that included an analysis of the association of gender with bladder cancer was performed using Pubmed. Ninety-seven articles were selected for analysis with the consensus of all authors. It has been shown that the gender difference in bladder cancer incidence is independent of differences in exposure risk, including smoking status. Potential molecular mechanisms include disparate metabolism of carcinogens by hepatic enzymes between men and women, resulting in differential exposure of the urothelium to carcinogens. In addition, the activity of the sex steroid hormone pathway may play a role in bladder cancer development, with demonstration that both androgens and estrogens have biologic effects in bladder cancer in vitro and in vivo. Importantly, gender differences exist in the timeliness and completeness of hematuria evaluation, with women experiencing a significantly greater delay in urologic referral and undergoing guideline-concordant imaging less frequently. Correspondingly, women have more advanced tumors at the time of bladder cancer diagnosis. Interestingly, higher cancer-specific mortality has been noted among women even after adjusting for tumor stage and treatment modality. Numerous potential biologic and epidemiologic factors probably underlie the gender differences observed for bladder cancer incidence, stage at diagnosis, and outcomes. Continued evaluation to define clinical applications for manipulation of the sex steroid pathway and to improve the standardization of hematuria

  8. High resolution photoacoustic imaging of microvasculature in normal and cancerous bladders

    Science.gov (United States)

    Xie, Zhixing; Roberts, William; Carson, Paul L.; Liu, Xiaojun; Tao, Chao; Wang, Xueding

    2013-03-01

    We explored the potential of an emerging laser-based technology, photoacoustic imaging (PAI), for bladder cancer diagnosis through high resolution imaging of microvasculature in the interior bladder tissues. Images of ex vivo canine bladders demonstrated the excellent ability of PAI to map three-dimensional microvasculature in optically scattering bladder tissues. By comparing the results from human bladder specimens affected by cancer to those from the normal control, the feasibility of PAI in differentiating malignant from benign bladder tissues was explored. The reported distinctive morphometric characteristics of tumor microvasculature can be seen in the images from cancer samples, suggesting that PAI may allow in vivo assessment of neoangiogenesis that is closely associated with bladder cancer generation and progression. By presenting subsurface morphological and physiological information in bladder tissues, PAI, when performed in a similar way to that in conventional endoscopy, provides an opportunity for improved diagnosis, staging and treatment guidance of bladder cancer.

  9. Developments in bladder cancer

    International Nuclear Information System (INIS)

    Denis, L.; Niijima, T.; Prout, G.; Schroder, F.H.

    1986-01-01

    This book contains 20 selections. Some of the titles are: Guidelines for Radiation Therapy in Clinical Research on Bladder Cancer; Transitional Cell Carcinoma in Situ; Policy on Monitoring and Reporting Results; Standardization of Protocol Formnd The Role of Cytology in the Diagnosis, Detection and Follow-up of Bladder Cancer

  10. 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...

  11. Ultrasound: Bladder (For Parents)

    Science.gov (United States)

    ... If You Have Questions Print en español Ultrasonido: vejiga What It Is A bladder ultrasound is a safe and painless test that ... Exam: Voiding Cystourethrogram (VCUG) Ultrasound: Renal (Kidneys, Ureters, Bladder) Urinary ... only. For specific medical advice, diagnoses, and treatment, consult your doctor. © 1995- The Nemours Foundation. All ...

  12. NMR imaging of bladder tumors in males. Preliminary clinical experience

    International Nuclear Information System (INIS)

    Sigal, R.; Rein, A.J.J.T.; Atlan, H.; Lanir, A.; Kedar, S.; Segal, S.

    1985-01-01

    Nuclear magnetic resonance (NMR) of the normal and pathologic bladder was performed in 10 male subjects: 5 normal volunteers, 4 with bladder primary carcinoma, 1 with bladder metastasis. All scanning was done using a superconductive magnet operating at 0.5 T. Spin echo was used as pulse sequence. The diagnosis was confirmed in all cases by NMR imaging. The ability of the technique to provide images in axial, sagital and coronal planes allowed a precise assessment of the morphology and the size of the tumors. The lack of hazards and the quality of images may promote NMR imaging to a prominent role in the diagnosis of human bladder cancer [fr

  13. An endogenous ribonuclease inhibitor regulates the antimicrobial activity of ribonuclease 7 in the human urinary tract

    Science.gov (United States)

    Spencer, John David; Schwaderer, Andrew L.; Eichler, Tad; Wang, Huanyu; Kline, Jennifer; Justice, Sheryl S.; Cohen, Daniel M.; Hains, David S.

    2013-01-01

    Recent studies stress the importance of antimicrobial peptides in protecting the urinary tract from infection. Previously, we have shown that ribonuclease 7 (RNase 7) is a potent antimicrobial peptide that has broad-spectrum antimicrobial activity against uropathogenic bacteria. The urothelium of the lower urinary tract and intercalated cells of the kidney produce RNase 7 but regulation of its antimicrobial activity has not been well defined. Here we characterize the expression of an endogenous inhibitor, ribonuclease inhibitor (RI), in the urinary tract and evaluate its effect on RNase 7’s antimicrobial activity. Using RNA isolated from non-infected human bladder and kidney tissue, quantitative real-time PCR showed that RNH1, the gene encoding RI, is constitutively expressed throughout the urinary tract. With pyelonephritis, RNH1 expression and RI peptide production significantly decrease. Immunostaining localized RI production to the umbrella cells of the bladder and intercalated cells of the renal collecting tubule. In vitro assays showed that RI bound to RNase 7 and suppressed its antimicrobial activity by blocking its ability to bind the cell wall of uropathogenic bacteria. Thus, these results demonstrate a new immunomodulatory role for RI and identified a unique regulatory pathway that may affect how RNase 7 maintains urinary tract sterility. PMID:24107847

  14. Bladder Cancer—Patient Version

    Science.gov (United States)

    The most common type of bladder cancer is transitional cell carcinoma, also called urothelial carcinoma. Smoking is a major risk factor for bladder cancer. Bladder cancer is often diagnosed at an early stage. Start here to find information on bladder cancer treatment, screening, research, and statistics.

  15. Onabotulinumtoxin type A improves lower urinary tract symptoms and quality of life in patients with human T cell lymphotropic virus type 1 associated overactive bladder

    Directory of Open Access Journals (Sweden)

    Jose Abraão Carneiro Neto

    2018-03-01

    Full Text Available Aim: To evaluate the efficacy of the onabotulinum toxin type A in the treatment of HTLV-1 associated overactive bladder and its impact on quality of life (QoL. Methods: Case series with 10 patients with overactive bladder refractory to conservative treatment with anticholinergic or physical therapy. They received 200Ui of onabotulinumtoxin type A intravesically and were evaluated by overactive bladder symptoms score (OABSS and King's Health Questionnaire. Results: The mean (SD of the age was 52 + 14.5 years and 60% were female. All of them had confirmed detrusor overactivity on urodynamic study. Seven patients had HAM/TSP. The median and range of the OABSS was 13 (12–15 before therapy and decreased to 1.0 (0–12 on day 30 and to 03 (0–14 on day 90 (p < 0.0001. There was a significant improvement in 8 of the 9 domains of the King's Health Questionnaire after the intervention. Hematuria, urinary retention and urinary infection were the complications observed in 3 out of 10 patients. The mean time to request retreatment was 465 days. Conclusion: Onabotulinum toxin type A intravesically reduced the OABSS with last long effect and improved the quality of life of HTLV-1 infected patients with severe overactive bladder. Keywords: Overactive bladder, Onabotulinum toxin, HTLV-1

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

    Science.gov (United States)

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

    2016-01-01

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

  17. The mechanism of the growth-inhibitory effect of coxsackie and adenovirus receptor (CAR) on human bladder cancer: a functional analysis of car protein structure.

    Science.gov (United States)

    Okegawa, T; Pong, R C; Li, Y; Bergelson, J M; Sagalowsky, A I; Hsieh, J T

    2001-09-01

    The coxsackie and adenovirus receptor (CAR) is identified as a high-affinity receptor for adenovirus type 5. We observed that invasive bladder cancer specimens had significantly reduced CAR mRNA levels compared with superficial bladder cancer specimens, which suggests that CAR may play a role in the progression of bladder cancer. Elevated CAR expression in the T24 cell line (CAR-negative cells) increased its sensitivity to adenovirus infection and significantly inhibited its in vitro growth, accompanied by p21 and hypophosphorylated retinoblastoma accumulation. Conversely, decreased CAR levels in both RT4 and 253J cell lines (CAR-positive cells) promoted their in vitro growth. To unveil the mechanism of action of CAR, we showed that the extracellular domain of CAR facilitated intercellular adhesion. Furthermore, interrupting intercellular adhesion of CAR by a specific antibody alleviates the growth-inhibitory effect of CAR. We also demonstrated that both the transmembrane and intracellular domains of CAR were critical for its growth-inhibitory activity. These data indicate that the cell-cell contact initiated by membrane-bound CAR can elicit a negative signal cascade to modulate cell cycle regulators inside the nucleus of bladder cancer cells. Therefore, the presence of CAR cannot only facilitate viral uptake of adenovirus but also inhibit cell growth. These results can be integrated to formulate a new strategy for bladder cancer therapy.

  18. Stages of Bladder Cancer

    Science.gov (United States)

    ... above the waist. Tiny tubules in the kidneys filter and clean the blood . They take out waste ... to bladder cancer. Being exposed to paints, dyes, metals, or petroleum products in the workplace. Past treatment ...

  19. Bladder Diseases - Multiple Languages

    Science.gov (United States)

    ... PDF Health Information Translations Spanish (español) Expand Section Bladder Diseases: MedlinePlus Health Topic - English Enfermedades de la vejiga: Tema de salud de MedlinePlus - español (Spanish) National ...

  20. Bladder perforations in children

    African Journals Online (AJOL)

    2014-11-20

    Nov 20, 2014 ... Mean recovery time for patients was 15 days. ... fracture.[1,2] Isolated bladder perforations are rare, and they .... PA, perineal injury, pelvic fracture. Trauma .... Lower genitourinary injury and pelvic fractures in pediatric patients.

  1. Effects of YC-1 on hypoxia-inducible factor 1 alpha in hypoxic human bladder transitional carcinoma cell line T24 cells.

    Science.gov (United States)

    Li, Yangle; Zhao, Xiaokun; Tang, Huiting; Zhong, Zhaohui; Zhang, Lei; Xu, Ran; Li, Songchao; Wang, Yi

    2012-01-01

    It was the aim of this study to explore the effects of 3-(5'-hydroxymethyl-2'-furyl)-l-benzyl indazole (YC-1) on transcription activity, cell proliferation and apoptosis of hypoxic human bladder transitional carcinoma cells (BTCC), mediated by hypoxia-inducible factor 1α (HIF-1α). BTCC cell line T24 cells were incubated under normoxic or hypoxic conditions, adding different doses of YC-1. The protein expression of HIF-1α and HIF-1α-mediated genes was detected by Western blotting. RT-PCR was used to detect HIF-1α mRNA expression. Cell proliferation, apoptosis and migration activity were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry and transwell migration assay. The cells were pretreated by two ERK/p38 MAPK pathway-specific inhibitors, PD98059 or SB203580, and then incubated with YC-1 treatment under hypoxic condition. HIF-1α protein expression was detected by Western blotting. Hypoxic T24 cells expressed a higher level of HIF-1α, vascular endothelial growth factor, matrix metalloproteinases-2, B-cell lymphoma/leukemia-2 protein and HIF-1α mRNA compared with normoxic controls, in which the above-mentioned expression was downregulated by YC-1 in a dose-dependent manner. Cell proliferation and migration activity were inhibited while apoptosis was induced by YC-1 under hypoxic condition. Moreover, YC-1-downregulated HIF-1α expression was reversed by PD98059 and SB203580, respectively. YC-1 inhibits HIF-1α and HIF-1α-mediated gene expression, cell proliferation and migration activity and induces apoptosis in hypoxic BTCC. The ERK/p38 MAPK pathway may be involved in YC-1-mediated inhibition of HIF-1α. Copyright © 2011 S. Karger AG, Basel.

  2. HumanMethylation450K Array–Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Mark O Kitchen

    2018-01-01

    Full Text Available Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management. Patients and methods: A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG were also assessed by bisulphite Pyrosequencing. Results: Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values. Conclusions: This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease.

  3. Selective hydride generation- cryotrapping- ICP-MS for arsenic speciation analysis at picogram levels: analysis of river and sea water reference materials and human bladder epithelial cells

    Science.gov (United States)

    Matoušek, Tomáš; Currier, Jenna M.; Trojánková, Nikola; Saunders, R. Jesse; Ishida, María C.; González-Horta, Carmen; Musil, Stanislav; Mester, Zoltán; Stýblo, Miroslav; Dědina, Jiří

    2013-01-01

    An ultra sensitive method for arsenic (As) speciation analysis based on selective hydride generation (HG) with preconcentration by cryotrapping (CT) and inductively coupled plasma- mass spectrometry (ICP-MS) detection is presented. Determination of valence of the As species is performed by selective HG without prereduction (trivalent species only) or with L-cysteine prereduction (sum of tri- and pentavalent species). Methylated species are resolved on the basis of thermal desorption of formed methyl substituted arsines after collection at −196°C. Limits of detection of 3.4, 0.04, 0.14 and 0.10 pg mL−1 (ppt) were achieved for inorganic As, mono-, di- and trimethylated species, respectively, from a 500 μL sample. Speciation analysis of river water (NRC SLRS-4 and SLRS-5) and sea water (NRC CASS-4, CASS-5 and NASS-5) reference materials certified to contain 0.4 to 1.3 ng mL−1 total As was performed. The concentrations of methylated As species in tens of pg mL−1 range obtained by HG-CT-ICP-MS systems in three laboratories were in excellent agreement and compared well with results of HG-CT-atomic absorption spectrometry and anion exchange liquid chromatography- ICP-MS; sums of detected species agreed well with the certified total As content. HG-CT-ICP-MS method was successfully used for analysis of microsamples of exfoliated bladder epithelial cells isolated from human urine. Here, samples of lysates of 25 to 550 thousand cells contained typically tens pg up to ng of iAs species and from single to hundreds pg of methylated species, well within detection power of the presented method. A significant portion of As in the cells was found in the form of the highly toxic trivalent species. PMID:24014931

  4. Bladder cancer and schistosomiasis

    International Nuclear Information System (INIS)

    Zaghloul, M.S.

    2012-01-01

    Schistosoma-associated bladder cancer was believed, for several decades, to be a completely unique entity of disease, different from urothelial cancer. This was probably due to its distinct clinico pathologic and demographic features that varied from those of urothelial entity. The carcinogenesis is an extremely complex process resulting from the accumulation of many genetic and epigenetic changes leading to alterations in the cell proliferation regulation process. In bladder cancer, many of these carcinogenic cascades were not fully documented or somewhat conflicting. In spite of the efforts performed, much is still needed to explore the presence or absence of the carcinogenic difference with a different etiology. The control of schistosomiasis in certain countries and the subsequent decrease in the intensity of infestation showed changing of features approaching that of urothelial tumors. However the schistosoma-associated bladder cancer presented in more advanced stages than schistosoma-non associated urothelial cancer. More recently, data are gathered that, upon applying the same treatment protocol and management care, stage by stage comparison of the treatment end-results were found to be similar in bladder cancer patients with a different etiology. All treatment options; including radical cystectomy with or without adjuvant or neoadjuvant chemo- or radiotherapy or tri modality bladder preserving treatment seem to lead to similar end-results regardless of etiologic factor(s) implicated in bladder cancer development.

  5. Time- and temperature-dependent autolysis of urinary bladder epithelium during ex vivo preservation.

    Science.gov (United States)

    Erman, Andreja; Veranič, Peter

    2011-07-01

    Morphological and functional preservation of urinary bladder epithelium-urothelium after extirpation from an organism enables physiological studies of that tissue and provides the basis for successful organ transplantations. The aim of this study was to determine the optimal temperature for maintaining urothelium in ex vivo conditions. Mouse urinary bladders were kept at the three temperatures usually used for maintaining tissue during transportation: at the temperature of melting ice (1°C), at room temperature (22-24°C), and at the body temperature of most mammals (37°C). Autolytic structural changes were followed with electron microscopy, while destruction of cytoskeleton and intercellular junctions was observed by immunolabeling. The first ultrastructural changes, swelling of mitochondria and necrosis of individual cells, became evident 30 min after extirpation if the tissue was kept at 1°C. After 60 and 120 min in ex vivo conditions, the most severe changes with increasing plasma membrane ruptures were detected at 1°C, while at room temperature only mild changes were detected. At 37°C, the extent of ultrastructural changes was between those of the other two experimental temperatures. Autolytic destruction of cytoskeleton and intercellular junctions was not observed before 2 h after extirpation. After 4 h, severe degradation of cytokeratin 20 and microtubules were found at 1°C and 37°C, while being almost undisturbed at room temperature. On the other hand, the reduction of desmoplakin and ZO-1 labeling was more evident at 37°C than at 1°C and room temperature. These findings provide evidence that room temperature is most appropriate for short ex vivo preservation of urothelial tissue.

  6. Urothelial melanosis of the bladder.

    Science.gov (United States)

    Valente, Sara L; Bieniek, Jared M; Kesler, Stuart S

    2017-10-01

    Urothelial melanosis is a rare finding characterized by abnormal pigmentation noted on cystoscopic evaluation and histologically defined by melanin deposition in the urothelium. Although generally considered benign, few cases of urothelial melanosis have been reported in the literature and the risk of recurrence or progression remains largely unknown. Four cases associated with urothelial cell carcinoma have been previously described. Here, we report a case of urothelial melanosis and review previously published cases in the literature.

  7. Increased CYP1A1 expression in human exfoliated urothelial cells of cigarette smokers compared to non-smokers

    Energy Technology Data Exchange (ETDEWEB)

    Doerrenhaus, Angelika; Roos, Peter H. [Institute for Occupational Physiology at the University Dortmund, Dortmund (Germany); Mueller, Tina [Institute for Occupational Physiology at the University Dortmund, Dortmund (Germany); University Dortmund, Department of Statistics, Mathematical Statistics with Applications in Biometrics, Dortmund (Germany)

    2007-01-15

    Polycyclic aromatic hydrocarbons, arylamines and nitrosamines, constituents of cigarette smoke, are known inducers of bladder cancer. The biochemical response of the target tissue, the bladder urothelium, following inhalation of cigarette smoke has not been studied so far. We used exfoliated transitional urothelial cells from human urine samples to analyze effects of smoking on induction of the cytochrome P450 enzyme CYP1A1. Samples of 40 subjects, including male and female smokers and non-smokers, were examined. A prerequisite for the immunofluorescence microscopic analysis of the cells was the enrichment of the urothelial cell population. This was achieved by a new method which is based on magnetic cell sorting exploiting specific binding of immobilized Griffonia simplicifolia lectin to the surface of urothelial cells. Immunostaining of the final cell preparation with a monoclonal antibody to CYP1A1 showed that about 6% of the urothelial cells of non-smokers stained positive for CYP1A1. However, this fraction of positive cells was more than 44% of the urothelial cells in samples from cigarette smokers. In spite of the individual variation, the difference was statistically significant. There were no gender-related differences in the portion of CYP1A1 expressing urothelial cells of smokers and non-smokers. In essence, we show for the first time that human urothelial cells respond to cigarette smoking by induction of CYP1A1. The approach opens new fields of mechanistic and biomarker research with respect to the pathogenetic processes of cancer development in the human bladder. (orig.)

  8. Bladder changes after several coverage modalities in the surgically induced model of myelomeningocele in lambs.

    Science.gov (United States)

    Burgos, L; Encinas, J L; García-Cabezas, M Á; Peiró, J L; López-Santamaría, M; Jaureguízar, E

    2014-01-01

    To assess the presence of early bladder abnormalities in a prenatally corrected and uncorrected animal model of Myelomeningocele (MMC). A MMC-like lesion was surgically created in 18 fetal lambs between the 60th and the 80th day of gestation. Eight of them did not undergo fetal repair (group A), three were repaired with an open two-layer closure (group B), three using BioGlue® (groupC) and four fetoscopically (group D). At term, bladders were examined macroscopically and histopathological changes were assessed using H-E and Masson Trichrome. Five animals in group A (5/8, 62%), two in group B (2/3, 66%), one in group C (1/3, 33%) and one in group D (1/4, 25%) survived. Macroscopically bladders in group A were severely dilated and showed thinner walls. Microscopically they showed a thin layer of colagenous tissue (Blue layer. BL) lying immediately subjacent to the urothelium. The muscular layers were thinner. Non compliant pattern with thick wall and low capacity was also found in the non corrected model. Group B and the control showed preservation of muscular layers and absence of BL. Groups C and D presented BL but also preservation of muscular layers. Bladder changes in a surgically-induced model of MMC can be described using histopathological data. Both extremes of bladder changes can be observed in the model. These changes were completely prevented with open fetal surgery and partially with other coverage modalities. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  9. A new problem in inflammatory bladder diseases: Use of mobile phones!

    Directory of Open Access Journals (Sweden)

    Orhan Koca

    2014-08-01

    Full Text Available Purpose Technological developments provide a lot of conveniences to our lives. This issue is one of the risks that arise along with these conveniences. In our study we tried to understand the impact of electromagnetic waves from mobile phones on bladder tissue. Materials and Methods Twenty-one adult male albino rats were divided into three equal groups. Group 1 was exposed to electromagnetic wave for 8 hours per day for 20 days and then their bladders were taken off immediately. Group 2 was firstly exposed to electromagnetic wave for 8 hours per day for 20 days then secondly another for 20 days without exposition to electromagnetic wave and then their bladders were taken off. Group 3 was the control group and they were not exposed to electromagnetic wave. Results Under microscopic examination of bladder tissue, in the first group severe inflammatory cell infiltration was seen in lamina propria and muscle layer in contrast to intact urothelium. In the second group mild inflammatory cell infiltration was seen in lamina propria and muscle layer. The mean scores for the three groups were 5.5 ± 2.5, 0.8 ± 1.3 and 1.2 ± 1.5 respectively. Mean score of group 1 was statistically higher than others (p = 0.001. Conclusion Intensive use of mobile phones has negative impact on bladder tissue as well as the other organs. Keeping a minimum level of mobile phone use makes it easy to be kept under control of diseases in which inflammation is an etiologic factor.

  10. Spontaneous Bladder Perforation in an Infant Neurogenic Bladder: Laparoscopic Management

    Directory of Open Access Journals (Sweden)

    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. Baicalein and U0126 suppress bladder cancer proliferation via ...

    African Journals Online (AJOL)

    (U0126)effects on human bladder cell line T24 proliferation and related mechanisms. Methods: Twenty ... pressure, stress, ionizing radiation, and oxidative damage. Activated JNK can ..... indirect regulation of ERK signals by JNK/p38 selective.

  12. Identification of Novel Gene Targets and Putative Regulators of Arsenic-Associated DNA Methylation in Human Urothelial Cells and Bladder Cancer

    Science.gov (United States)

    Rager, Julia E.; Miller, Sloane; Tulenko, Samantha E.; Smeester, Lisa; Ray, Paul D.; Yosim, Andrew; Currier, Jenna M.; Ishida, María C.; González-Horta, Maria del Carmen; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Gutiérrez-Torres, Daniela S.; Drobná, Zuzana; Del Razo, Luz M.; García-Vargas, Gonzalo G.; Kim, William Y.; Zhou, Yi-Hui; Wright, Fred A.; Stýblo, Miroslav; Fry, Rebecca C.

    2016-01-01

    There is strong epidemiologic evidence linking chronic exposure to inorganic arsenic (iAs) to a myriad of adverse health effects, including cancer of the bladder. The present study set out to identify DNA methylation patterns associated with iAs and its metabolites in exfoliated urothelial cells (EUCs) that originate primarily from the urinary bladder, one of the targets of arsenic (As)-induced carcinogenesis. Genome-wide, gene-specific promoter DNA methylation levels were assessed in EUCs from 46 residents of Chihuahua, Mexico, and the relationship was examined between promoter methylation profiles and the intracellular concentrations of total As (tAs) and As species. A set of 49 differentially methylated genes was identified with increased promoter methylation associated with EUC tAs, iAs, and/or monomethylated As (MMAs) enriched for their roles in metabolic disease and cancer. Notably, no genes had differential methylation associated with EUC dimethylated As (DMAs), suggesting that DMAs may influence DNA methylation-mediated urothelial cell responses to a lesser extent than iAs or MMAs. Further analysis showed that 22 of the 49 As-associated genes (45%) are also differentially methylated in bladder cancer tissue identified using The Cancer Genome Atlas repository. Both the As- and cancer-associated genes are enriched for the binding sites of common transcription factors known to play roles in carcinogenesis, demonstrating a novel potential mechanistic link between iAs exposure and bladder cancer. PMID:26039340

  13. Review of underactive bladder

    Directory of Open Access Journals (Sweden)

    Yi-Huei Chang

    2018-03-01

    Full Text Available In clinical practice, many patients cannot empty their bladders within an acceptable duration. Common complaints include weak urinary stream and incomplete emptying, which may affect quality of life. Bladder emptying requires sufficient detrusor contractile power, velocity, and durability. The urodynamic term for inadequate detrusor contraction is detrusor underactivity (DU. Although this definition was provided by the ICS, it may not be clinically practical. Analogous to the relationship between overactive bladder (OAB and detrusor overactivity (DO, the symptom complex caused by DU is termed underactive bladder (UAB. Many conditions lead to UAB, such as advanced age, neurogenic bladder and BOO, but the definite pathophysiology directly leading to UAB is still being widely studied without a widely-accepted consensus. The preferred mainstream treatment for increased residual urine volume caused by UAB is intermittent catheterization, while pharmacotherapy is still disappointing after decades of development. There are no studies on surgical treatment for UAB with an acceptable level of evidence. We reviewed the recent literature on UAB and DU to provide a comprehensive discussion of the related presentation, etiology, diagnosis and management.

  14. Genetics Home Reference: bladder cancer

    Science.gov (United States)

    ... Testing Registry: Malignant tumor of urinary bladder Other Diagnosis and Management Resources (1 link) MedlinePlus Encyclopedia: Bladder Cancer General Information from MedlinePlus (5 links) Diagnostic Tests ...

  15. Pseudocarcinomatous epithelial hyperplasia in the bladder unassociated with prior irradiation or chemotherapy.

    Science.gov (United States)

    Lane, Zhaoli; Epstein, Jonathan I

    2008-01-01

    Pseudocarcinomatous epithelial hyperplasia in the bladder is a little known phenomenon, recognized to be associated with prior irradiation and/or chemotherapy. Whether this process can occur outside of this setting has not been studied. We identified 8 of these cases mimicking invasive urothelial carcinoma from our consultation files from 07/04 to 07/06 with no prior history of radiation or chemotherapy. The mean age at diagnosis was 65 years (range, 42 to 81 y), with 5 of the 8 males. Seven patients had a potential etiology for these changes that could either have resulted in localized ischemia or injury to the urothelium. These included case 1: atrial fibrillation, hypertension, congestive heart failure, gastrointestinal bleeding, and coronary artery vascular disease; case 2: coronary angioplasty, atrial fibrillation, hyperlipidemia, and amputation of arm for ischemia; case 3: hypertension, uncontrolled diabetes, hyperlipidemia, and atrial fibrillation; case 4: underlying arteriovenous malformation of the bladder; cases 5 to 6: history of indwelling Foley catheter; and case 7: history of radical prostatectomy for prostate cancer but no radiation. One patient had no potential contributing factors. All 8 patients presented with gross hematuria. At cystoscopy, 7 patients had polypoid lesions with 1 appearing nonpolypoid. Histologically, all cases showed epithelial proliferation of urothelium with cells having prominent eosinophilic cytoplasm. This process that mimicked invasive cancer within the lamina propria was marked in 3 cases (38%). Moderate nuclear pleomorphism was seen in 6 cases (75%). Only 1 case revealed mitotic figures. Ulceration was seen in 1 case. All cases showed some degree of hemorrhage with hemosiderin deposition identified in 3 cases (38%). Fibrin deposition was present in 1 case within the stroma, 3 cases in the vessels, and 4 cases in both. Five cases show stromal fibrosis. Edema and vascular congestion were common features (90% and 100

  16. A BAC-based transgenic mouse specifically expresses an inducible Cre in the urothelium.

    Directory of Open Access Journals (Sweden)

    Tian Huai Shen

    Full Text Available Cre-loxp mediated conditional knockout strategy has played critical roles for revealing functions of many genes essential for development, as well as the causal relationships between gene mutations and diseases in the postnatal adult mice. One key factor of this strategy is the availability of mice with tissue- or cell type-specific Cre expression. However, the success of the traditional molecular cloning approach to generate mice with tissue specific Cre expression often depends on luck. Here we provide a better alternative by using bacterial artificial chromosome (BAC-based recombineering to insert iCreERT2 cDNA at the ATG start of the Upk2 gene. The BAC-based transgenic mice express the inducible Cre specifically in the urothelium as demonstrated by mRNA expression and staining for LacZ expression after crossing with a Rosa26 reporter mouse. Taking into consideration the size of the gene of interest and neighboring genes included in a BAC, this method should be widely applicable for generation of mice with tissue specific gene expression or deletions in a more specific manner than previously reported.

  17. [Effect of hydrostatic pressure on intracellular free calcium concentration and transient receptor potential vanilloid expression in human bladder smooth muscle cells].

    Science.gov (United States)

    Han, Zhenwei; Wang, Kunjie; Chen, Lin; Wei, Tangqiang; Luo, Deyi; Li, Shengfu

    2012-04-01

    To explore the effect of hydrostatic pressure on intracellular free calcium concentration ([Ca2+]i) and the gene expression of transient receptor potential vanilloid (TRPV) in cultured human bladder smooth muscle cells (hb-SMCs), and to preliminarily probe into the possible molecular mechanism of hb-SMCs proliferation stimulated by hydrostatic pressure. The passage 6-7 hb-SMCs were loaded with Ca2+ indicator Fluo-3/AM. When the hb-SMCs were under 0 cm H2O (1cm H2O = 0.098 kPa) (group A) or 200 cm H2O hydrostatic pressure for 30 minutes (group B) and then removing the 200 cm H2O hydrostatic pressure (group C), the [Ca2+]i was measured respectively by inverted laser scanning confocal microscope. When the hb-SMCs were given the 200 cm H2O hydrostatic pressure for 0 hour, 2 hours, 6 hours, 12 hours, and 24 hours, the mRNA expressions of TRPV1, TRPV2, and TRPV4 were detected by RT-PCR technique. The [Ca2+]i of group A, group B, and group C were (100.808 +/- 1.724), (122.008 +/- 1.575), and (99.918 +/- 0.887) U, respectively; group B was significantly higher than groups A and C (P pressure (t = 0.919, P = 0.394). The TRPV1, TRPV2, and TRPV4 genes expressed in hb-SMCs under 200 cm H2O hydrostatic pressure at 0 hour, 2 hours, 6 hours, 12 hours, and 24 hours, but the expressions had no obvious changes with time. There was no significant difference in the expressions of TRPV1, TRPV2, and TRPV4 among 3 groups (P > 0.05). The [Ca2+]i of hb-SMCs increases significantly under high hydrostatic pressure. As possible genes in stretch-activated cation channel, the TRPV1, TRPV2, and TRPV4 express in hb-SMCs under 200 cm H2O hydrostatic pressure. It is possible that the mechanical pressure regulates the [Ca2+]i of hb-SMCs by opening the stretch-activated cation channel rather than up-regulating its expression.

  18. Role of Nicotinic Acetylcholine Receptor α3 and α7 Subunits in Detrusor Overactivity Induced by Partial Bladder Outlet Obstruction in Rats

    Directory of Open Access Journals (Sweden)

    Hyo Sin Kim

    2015-03-01

    Full Text Available Purpose: To investigate the role of α3 and α7 nicotinic acetylcholine receptor subunits (nAChRs in the bladder, using a rat model with detrusor overactivity induced by partial bladder outlet obstruction (BOO. Methods: Forty Sprague-Dawley rats were used: 10 were sham-operated (control group and 30 were observed for 3 weeks after partial BOO. BOO-induced rats were further divided into 3 groups: Two groups of 10 rats each received intravesicular infusions with hexamethonium (HM group; n=10 or methyllycaconitine (MLC group; n=10, which are antagonists for α3 and α7 nAChRs, respectively. The remaining BOO-induced rats received only saline infusion (BOO group; n=10. Based on the contraction interval measurements using cystometrogram, the contraction pressure and nonvoiding bladder contractions were compared between the control and the three BOO-induced groups. Immunofluorescent staining and Western blotting were used to analyze α3 and α7 nAChRs levels. Results: The contraction interval of the MLC group was higher than that of the BOO group (P<0.05. Nonvoiding bladder contraction almost disappeared in the HM and MLC groups. Contraction pressure increased in the BOO group (P<0.05 compared with the control group and decreased in the HM and MLC groups compared with the BOO group (P<0.05. Immunofluorescence staining showed that the α3 nAChR signals increased in the urothelium, and the α7 nAChR signals increased in the urothelium and detrusor muscle of the BOO group compared with the control group. Western blot analysis showed that both α3 and α7 nAChR levels increased in the BOO group (P<0.05. Conclusions: Alpha3 and α7 nAChRs are associated with detrusor overactivity induced by BOO. Furthermore, nAChR antagonists could help in clinically improving detrusor overactivity.

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

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    Bishop D Timothy

    2008-07-01

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

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

    Science.gov (United States)

    Wadhwa, N; Mathew, B B; Jatawa, S K; Tiwari, A

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    N Wadhwa

    2013-01-01

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

  2. Radiotherapy of bladder cancer

    International Nuclear Information System (INIS)

    Ikeda, Yoshiyuki

    1978-01-01

    Methods of treating bladder cancer include surgery, radiotherapy and chemotherapy, as well as various combinations of these. The author investigated clinically and histopathologically the therapeutic results of preoperative irradiation in cases of bladder cancer. 1. The survival rates (crude survival rates) in forty cases of bladder cancer were 90% after one year, 62.5% after three years and 46% after five years from the treatment. 2. As the result of irradiation, urogram improved in 25%, which was comparatively remarkable in high stage cases. There were no cases of deterioration of urogram findings caused by irradiation. Cystoscopy revealed disappearance or remarkable shrinkage of the tumors in 35% of the total cases and effects of the irradiation was observed not correlated to the stage and grade. 3. With respect to the histopathological changes, the changes became greater as the dosage increased and the higher the stage and grade were the more remarkable tendency was observed. 4. From our clinical observations such as urogram, cystoscopy and histopathologically, we estimated the optimum dosage of preoperative irradiation for bladder cancer is 3000 - 4000 rad. Thus, we concluded that the radiotherapy is effective in reducing both surgical invasion and postoperative recurrence. (author)

  3. 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.

  4. Taurine modulates neutrophil function but potentiates uropathogenic E. coli infection in the murine bladder.

    LENUS (Irish Health Repository)

    Condron, Claire

    2010-08-01

    Eradication of a urinary tract infection (UTI) appears to be related to a number of innate host defence mechanisms and their interactions with invading bacteria. Recurrent UTIs (rUTIs) pose a difficult problem in that these bacteria use both host and bacterial factors to evade elimination. Neutrophil bactericidal function is depressed, both systemically and in urine, in patients with a history of recurrent UTI. Taurine is a semi-essential amino acid and is successful in preserving neutrophil bactericidal function in urine. Taurine may preserve neutrophil function at the urothelium and thus aid UTI resolution. Adult female (6 weeks old) C57Bl\\/6 mice were randomised into three groups: a saline gavage only control group, a saline gavage + E. coli group, and a taurine gavage + E. coli group [21 g\\/70 kg taurine in 0.9% normal saline (N\\/S) for 5 days]. Whilst taurine gavage pre-treatment resulted in increased serum neutrophils respiratory burst activity, at the urothelial-endothelial interface it caused higher colony forming units in the urine and a higher incidence of E. coli invasion in the bladder wall with no evidence of increased bladder wall neutrophils infiltration on MPO assay of histological assessment. Histologically there was also evidence of reduced bladder inflammation and urothelial cell apoptosis. In conclusion, taurine effectively increases neutrophils activity but given its anti-inflammatory properties, at the expense of decreased urothelial-endothelial activation thus preventing clearance of active E. coli infection in the bladder. Despite the negative results, this study demonstrates the importance of modulating interactions at the urothelial interface.

  5. Flaccidoxide-13-Acetate Extracted from the Soft Coral Cladiella kashmani Reduces Human Bladder Cancer Cell Migration and Invasion through Reducing Activation of the FAK/PI3K/AKT/mTOR Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Choo-Aun Neoh

    2017-12-01

    Full Text Available Metastasis of cancer is the cause of the majority of cancer deaths. Active compound flaccidoxide-13-acetate, isolated from the soft coral Cladiella kashmani, has been found to exhibit anti-tumor activity. In this study, Boyden chamber analysis, Western blotting and gelatin zymography assays indicated that flaccidoxide-13-acetate exerted inhibitory effects on the migration and invasion of RT4 and T24 human bladder cancer cells. The results demonstrated that flaccidoxide-13-acetate, in a concentration-dependent manner, reduced the levels of matrix metalloproteinase-2 (MMP-2, MMP-9, urokinase-type plasminogen activator receptor (uPAR, focal adhesion kinase (FAK, phosphatidylinositide-3 kinases (PI3K, p-PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR, p-mTOR, Ras homolog gene family, member A (Rho A, Ras, mitogen-activated protein kinase kinase 7 (MKK7 and mitogen-activated protein kinase kinase kinase 3 (MEKK3, and increased the expressions of tissue inhibitor of metalloproteinase-1 (TIMP-1 and TIMP-2 in RT4 and T24 cells. This study revealed that flaccidoxide-13-acetate suppressed cell migration and invasion by reducing the expressions of MMP-2 and MMP-9, regulated by the FAK/PI3K/AKT/mTOR pathway. In conclusion, our study was the first to demonstrate that flaccidoxide-13-acetate could be a potent medical agent for use in controlling the migration and invasion of bladder cancer.

  6. Loss of intercellular adhesion leads to differential accumulation of hypericin in bladder cancer

    Science.gov (United States)

    Lucky, S. Sasidharan; Bhuvaneswari, Ramaswamy; Chin, William W. L.; Lau, Weber K. O.; Olivo, Malini C. D.

    2009-06-01

    Photodynamic diagnosis (PDD) exploits the photoactive nature of certain compounds, namely photosensitizers, in order to enhance the visual demarcation between normal and neoplastic tissue. Hypericin is one such potent photosensitizer that preferentially accumulate in neoplastic tissue, and fluoresce in the visible spectrum when illuminated with light of an appropriate wavelength. In our study, we investigated the role of E-cadherin in the selective permeation of hypericin in bladder cancer tissues. Clinical studies were done on a series of 43 histologically graded bladder cancer biopsy specimens, obtained from 28 patients who received intravesical instillations with 8μM hypericin solution for at least 2 hours. Immunohistochemical staining was used to assess the expression of E-cadherin, in the cryosectioned tissues. Hypericin uptake was examined by fluorescence microscopy. Immunohistochemical staining showed a clear expression of E-cadherin along the urothelial lining of the normal and pre-malignant tissues. Partial expression of these cell adhesion molecules were still observed in malignant tissues, however there was a loss of expression to variable extends along the urothelium. Thus, loss of intercellular adhesion can be associated with enhanced hypericin permeation through paracellular diffusion.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  8. Radiotherapy in bladder cancer

    International Nuclear Information System (INIS)

    Rozan, R.

    1992-01-01

    In 1992, the problem of the vesical radiotherapy is not resolved. The author presents the situation and the different techniques of radiotherapy in bladder cancers: external radiotherapy, only and associated with surgery, interstitial curietherapy and non-classical techniques as per operative radiotherapy, neutron therapy and concurrent radiotherapy with chemotherapy. In order to compare their efficiency, the five-year survival are given in all cases.(10 tabs)

  9. Cystoscopic enucleation of bladder leiomyoma

    Directory of Open Access Journals (Sweden)

    Ghassan A Barayan

    2012-01-01

    Full Text Available We are presenting a rare case of bladder leiomyoma. A 61-year-old female patient was found to have a bladder mass during a work up of lower urinary tract symptoms. After full investigation, she underwent transurethral excision of the mass. The histopathology revealed typical feature of bladder leiomyoma. No recurrence was seen after a follow-up period of 12 months.

  10. Contemporary Management of Bladder Cancer

    Science.gov (United States)

    Bell, David; Fradet, Yves

    1991-01-01

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

  11. Growth delay of human bladder cancer cells by Prostate Stem Cell Antigen downregulation is associated with activation of immune signaling pathways

    Directory of Open Access Journals (Sweden)

    Nicosia Alfredo

    2010-04-01

    Full Text Available Abstract Background Prostate stem cell antigen (PSCA is a glycosylphosphatidylinositol (GPI anchored protein expressed not only in prostate but also in pancreas and bladder cancer as shown by immunohistochemistry and mRNA analysis. It has been targeted by monoclonal antibodies in preclinical animal models and more recently in a clinical trial in prostate cancer patients. The biological role played in tumor growth is presently unknown. In this report we have characterized the contribution of PSCA expression to tumor growth. Methods A bladder cell line was engineered to express a doxycycline (dox regulated shRNA against PSCA. To shed light on the PSCA biological role in tumor growth, microarray analysis was carried out as a function of PSCA expression. Expression of gene set of interest was further analyzed by qPCR Results Down regulation of the PSCA expression was associated with reduced cell proliferation in vitro and in vivo. Mice bearing subcutaneous tumors showed a reduced tumor growth upon treatment with dox, which effectively induced shRNA against PSCA as revealed by GFP expression. Pathway analysis of deregulated genes suggests a statistical significant association between PSCA downregulation and activation of genes downstream of the IFNα/β receptor. Conclusions These experiments established for the first time a correlation between the level of PSCA expression and tumor growth and suggest a role of PSCA in counteracting the natural immune response.

  12. Growth delay of human bladder cancer cells by Prostate Stem Cell Antigen downregulation is associated with activation of immune signaling pathways

    International Nuclear Information System (INIS)

    Marra, Emanuele; Ciliberto, Gennaro; Palombo, Fabio; Uva, Paolo; Viti, Valentina; Simonelli, Valeria; Dogliotti, Eugenia; De Rinaldis, Emanuele; Lahm, Armin; La Monica, Nicola; Nicosia, Alfredo

    2010-01-01

    Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI) anchored protein expressed not only in prostate but also in pancreas and bladder cancer as shown by immunohistochemistry and mRNA analysis. It has been targeted by monoclonal antibodies in preclinical animal models and more recently in a clinical trial in prostate cancer patients. The biological role played in tumor growth is presently unknown. In this report we have characterized the contribution of PSCA expression to tumor growth. A bladder cell line was engineered to express a doxycycline (dox) regulated shRNA against PSCA. To shed light on the PSCA biological role in tumor growth, microarray analysis was carried out as a function of PSCA expression. Expression of gene set of interest was further analyzed by qPCR Down regulation of the PSCA expression was associated with reduced cell proliferation in vitro and in vivo. Mice bearing subcutaneous tumors showed a reduced tumor growth upon treatment with dox, which effectively induced shRNA against PSCA as revealed by GFP expression. Pathway analysis of deregulated genes suggests a statistical significant association between PSCA downregulation and activation of genes downstream of the IFNα/β receptor. These experiments established for the first time a correlation between the level of PSCA expression and tumor growth and suggest a role of PSCA in counteracting the natural immune response

  13. OVERACTIVE BLADDER SYNDROME IN CHILDREN

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    E.L. Vishnevskiy

    2007-01-01

    Full Text Available Overactive bladder is a specific syndrome characterized by bladder dysfunction that is clinically manifested by imperative urination (pollakiuria, urgency, urgent incontinence and nocturia. This state is very widely spread among children: every fifth child aged 4 to 7 shows typical bladder dysfunction. Quite often if urinary distresses are not studied well enough such children are falsely diagnosed with monosymptom enuresis, which, according to our information, actually happens in only 3,9% of cases. When examining children with urinary disorders it is reasonable to be geared to the protocol of European urologist association. According to this protocol, treatment should be started with antimuscarinimedications. The only antimuscarinic medication for treating children with hyperactive bladder that is legal in Russia is oxybutinin (Driptane, that is presently considered to be the «golden standard» of pharmaceutical treatment of overactive bladder for patients of any age. This statement is based on the modern idea of overactive bladder pathogenesis, that presupposes detrusorhypersensibility to acetylcholine. However, in some cases it might be reasonable to use some other medications, physiotherapy, sometimes as part of complex therapy. If individual dosage is observed, which will enable preventing or significantly lowering possible side effects, oxybutinin will be still considered «the golden standard» for treating overactive bladder for years to come in cases when detrusor hypersensibility to acetylcholine is the key component of bladder dysfunction pathogenesis.Key words: overactive bladder, oxybutinin, urination disorder, children.

  14. Molecular biology of bladder cancer.

    Science.gov (United States)

    Martin-Doyle, William; Kwiatkowski, David J

    2015-04-01

    Classic as well as more recent large-scale genomic analyses have uncovered multiple genes and pathways important for bladder cancer development. Genes involved in cell-cycle control, chromatin regulation, and receptor tyrosine and PI3 kinase-mammalian target of rapamycin signaling pathways are commonly mutated in muscle-invasive bladder cancer. Expression-based analyses have identified distinct types of bladder cancer that are similar to subsets of breast cancer, and have prognostic and therapeutic significance. These observations are leading to novel therapeutic approaches in bladder cancer, providing optimism for therapeutic progress. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Urinary Thromboxane B2 and Thromboxane Receptors in Bladder Cancer: Opportunity for Detection and Monitoring

    OpenAIRE

    Moussa, Omar; Ciupek, Andrew; Watson, Dennis K.; Halushka, Perry V.

    2011-01-01

    We have previously found increased expression of thromboxane synthase (TXAS) and thromboxane receptor (TP) beta isoform in the tissues of patients with bladder cancer. Studies in cell lines and mice have indicated a potential significant role of the thromboxane signaling pathway in the pathogenesis of human bladder cancer. This study was designed to determine if the changes observed in the tissues of patients with bladder cancer were mirrored by changes in the urine of these patients. We foun...

  16. Survivin Expression as a Predictive Marker for Local Control in Patients With High-Risk T1 Bladder Cancer Treated With Transurethral Resection and Radiochemotherapy

    International Nuclear Information System (INIS)

    Weiss, Christian; Roemer, Felix von; Capalbo, Gianni; Ott, Oliver J.; Wittlinger, Michael; Krause, Steffen F.; Sauer, Rolf; Roedel, Claus; Roedel, Franz

    2009-01-01

    Purpose: The objectives of this study were to investigate the expression of survivin in tumor samples from patients with high-risk T1 bladder cancer and to correlate its expression with clinicopathologic features as well as clinical outcomes after initial transurethral resection (TURBT) followed by radiotherapy (RT) or radiochemotherapy (RCT). Methods and Materials: Survivin protein expression was evaluated by immunohistochemistry on tumor specimen (n = 48) from the initial TURBT, and was correlated with clinical and histopathologic characteristics as well as with 5-year rates of local failure, tumor progression, and death from urothelial cancer after primary bladder sparring treatment with RT/RCT. Results: Survivin was not expressed in normal bladder urothelium but was overexpressed in 67% of T1 tumors. No association between survivin expression and clinicopathologic factors (age, gender, grading, multifocality, associated carcinoma in situ) could be shown. With a median follow-up of 27 months (range, 3-140 months), elevated survivin expression was significantly associated with an increased probability of local failure after TURBT and RCT/RT (p = 0.003). There was also a clear trend toward a higher risk of tumor progression (p = 0.07) and lower disease-specific survival (p = 0.10). Conclusions: High survivin expression is a marker of tumor aggressiveness and may help to identify a subgroup of patients with T1 bladder cancer at a high risk for recurrence when treated with primary organ-sparing approaches such as TURBT and RCT.

  17. Naftopidil inhibits 5-hydroxytryptamine-induced bladder contraction in rats.

    Science.gov (United States)

    Sakai, Takumi; Kasahara, Ken-ichi; Tomita, Ken-ichi; Ikegaki, Ichiro; Kuriyama, Hiroshi

    2013-01-30

    Naftopidil is an α(1D) and α(1A) subtype-selective α(1)-adrenoceptor antagonist that has been used to treat lower urinary tract symptoms of benign prostatic hyperplasia. In this study, we investigated the effects of naftopidil on 5-hydroxytryptamine (5-HT)-induced rat bladder contraction (10(-8)-10(-4) M). Naftopidil (0.3, 1, and 3 μM) inhibited 5-HT-induced bladder contraction in a concentration-dependent manner. On the other hand, other α(1)-adrenoceptor antagonists, tamsulosin, silodosin or prazosin, did not inhibit 5-HT-induced bladder contraction. The 5-HT-induced bladder contraction was inhibited by both ketanserin and 4-(4-fluoronaphthalen-1-yl)-6-propan-2-ylpyrimidin-2-amine (RS127445), serotonin 5-HT(2A) and 5-HT(2B) receptor antagonists, respectively. In addition, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and α-methyl-5-HT, 5-HT(2A) and 5-HT(2) receptor agonists, respectively, induced bladder contraction. The 5-HT-induced bladder contraction was not inhibited by N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-yl-cyclohexanecarboxamide (WAY-100635), [1-[2[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl-1-methyl-1H-indole-3-carboxylate (GR113808) or (R)-3-[2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulphonyl]phenol (SB269970), 5-HT(1A), 5-HT(4) and 5-HT(7) receptor antagonists, respectively. Naftopidil inhibited both the 5-HT(2A) and 5-HT(2) receptor agonists-induced bladder contractions. Naftopidil binds to the human 5-HT(2A) and 5-HT(2B) receptors with pKi values of 6.55 and 7.82, respectively. These results suggest that naftopidil inhibits 5-HT-induced bladder contraction via blockade of the 5-HT(2A) and 5-HT(2B) receptors in rats. Furthermore, 5-HT-induced bladder contraction was enhanced in bladder strips obtained from bladder outlet obstructed rats, with this contraction inhibited by naftopidil. The beneficial effects of naftopidil on storage symptoms such as urinary frequency and nocturia in patients with benign

  18. Traumatic injury of the bladder and urethra

    Science.gov (United States)

    ... disruption Images Bladder catheterization, female Bladder catheterization, male Female urinary tract Male urinary tract References Morey AF, Zhao LC. Genital and lower urinary tract trauma. In: Wein AJ, ...

  19. Intercellular transfer of P-glycoprotein from the drug resistant human bladder cancer cell line BIU-87 does not require cell-to-cell contact.

    Science.gov (United States)

    Zhou, Hui-liang; Zheng, Yong-jun; Cheng, Xiao-zhi; Lv, Yi-song; Gao, Rui; Mao, Hou-ping; Chen, Qin

    2013-09-01

    The efflux activity of transmembrane P-glycoprotein prevents various therapeutic drugs from reaching lethal concentrations in cancer cells, resulting in multidrug resistance. We investigated whether drug resistant bladder cancer cells could transfer functional P-glycoprotein to sensitive parental cells. Drug sensitive BIU-87 bladder cancer cells were co-cultured for 48 hours with BIU-87/ADM, a doxorubicin resistant derivative of the same cell line, in a Transwell® system that prevented cell-to-cell contact. The presence of P-glycoprotein in recipient cell membranes was established using fluorescein isothiocyanate, laser scanning confocal microscopy and Western blot. P-glycoprotein mRNA levels were compared between cell types. Rhodamine 123 efflux assay was done to confirm that P-glycoprotein was biologically active. The amount of P-glycoprotein protein in BIU-87 cells co-cultured with BIU-87/ADM was significantly higher than in BIU-87 cells (0.44 vs 0.25) and BIU-87/H33342 cells (0.44 vs 0.26, each p transfer. P-glycoprotein mRNA expression was significantly higher in BIU-87/ADM cells than in co-cultured BIU-87 cells (1.28 vs 0.30), BIU-87/H33342 (0.28) and BIU-87 cells (0.25, each p <0.001), ruling out a genetic mechanism. After 30 minutes of efflux, rhodamine 123 fluorescence intensity was significantly lower in BIU-87/ADM cells (5.55 vs 51.45, p = 0.004) and co-cultured BIU-87 cells than in BIU-87 cells (14.22 vs 51.45, p <0.001), indicating that P-glycoprotein was functional. Bladder cancer cells can acquire functional P-glycoprotein through a nongenetic mechanism that does not require direct cell contact. This mechanism is consistent with a microparticle mediated process. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  20. Intravesical Bacillus Calmette-Guérin therapy for murine bladder tumors: initiation of the response by fibronectin-mediated attachment of Bacillus Calmette-Guérin.

    Science.gov (United States)

    Ratliff, T L; Palmer, J O; McGarr, J A; Brown, E J

    1987-04-01

    Intravesical Bacillus Calmette-Guérin (BCG) is considered to be one of the most effective treatments for superficial bladder cancer. Although the mechanisms by which BCG inhibits tumor growth are not known, previous studies have shown that systemic immunization to BCG and the local expression of the immune response in the bladder are associated with a favorable response to BCG therapy. We have investigated the conditions required for the initiation of an immunological response after the intravesical instillation of BCG. Initial histological studies showed that BCG attached to the bladder wall only in areas where the urothelium was damaged by electrocautery and suggested that attachment was associated with the fibrin clot. Quantitative studies verified the histological observations. Minimal BCG attachment (mean less than 10(2) colony forming units) was observed in normal bladders in contrast with a mean of 1.42 X 10(4) colony forming units/bladder in bladders damaged by electrocautery (10 separate experiments). BCG attachment to the bladder wall was durable since organisms were observed in bladders 48 h after instillation. To investigate the proteins to which BCG attached, we tested the binding of BCG to extracellular matrix and inflammatory proteins which comprise a significant portion of the fibrin clot. BCG bound in vitro to coverslips coated in vivo with extracellular matrix proteins but did not bind to control albumin-coated coverslips. BCG also bound to coverslips coated with purified plasma fibronectin but not to coverslips coated with other purified extracellular matrix proteins including laminin, fibrinogen, and type IV collagen. BCG attachment to coverslips coated with either extracellular matrix proteins or purified fibronectin was inhibited by antibodies specific for fibronectin. Moreover, BCG attachment to cauterized bladders in vivo was inhibited by antifibronectin antibodies. These results demonstrate that fibronectin mediates the attachment of BCG

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

    Directory of Open Access Journals (Sweden)

    Carrie A. Franzen

    2014-01-01

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

  2. Effects of Physiotherapy in the Treatment of Neurogenic Bladder in Patients Infected with Human T-Lymphotropic Virus 1 (HTLV-1)

    Science.gov (United States)

    Andrade, Rosana C.P.; Neto, José A.; Andrade, Luciana; Oliveira, Tatiane S. S.; Santos, Dislene N.; Oliveira, Cassius J.V.; Prado, Márcio J.; Carvalho, Edgar M.

    2016-01-01

    Objective To evaluate the efficacy of physiotherapy for urinary manifestations in patients with HTLV-1-associated lower urinary tract dysfunction. Methods Open clinical trial with 21 patients attending the physiotherapy clinic of the Hospital Universitário, Bahia, Brazil. Combinations of behavioral therapy, perineal exercises and intravaginal/intra-anal electrical stimulation were used. Results The mean age was 54±12 years and 67% were female. After treatment, there was an improvement in symptoms of urinary urgency, frequency, incontinence, nocturia and in the sensation of incomplete emptying (pPhysiotherapy was effective in cases of HTLV-1-associated neurogenic bladder, reducing symptoms, increasing perineal muscle strength, improving urodynamic parameters and quality of life. PMID:26724409

  3. Tetrachloroethylene exposure and bladder cancer risk

    DEFF Research Database (Denmark)

    Vlaanderen, Jelle; Straif, Kurt; Ruder, Avima

    2014-01-01

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

  4. 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

  5. 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.)

  6. Postmortem MRI of bladder agenesis

    International Nuclear Information System (INIS)

    Barber, Brendan R.; Weber, Martin A.; Bockenhauer, Detlef; Hiorns, Melanie P.; McHugh, Kieran

    2011-01-01

    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.)

  7. Vulvar Metastasis from Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Fouad Aoun

    2015-01-01

    Full Text Available Vulvar metastasis of urothelial carcinoma of the bladder is a very rare entity; few cases are reported in the English literature. In this paper, we describe the clinical and pathological characteristics, evolution, and treatment of a patient with vulvar metastasis of urothelial carcinoma of the bladder followed by a brief review of the reported cases in the literature.

  8. Neuromodulation in bladder dysfunction.

    Science.gov (United States)

    Hasan, S T; Neal, D E

    1998-10-01

    Neuromodulation is one option for the management of a wide variety of lower urinary tract disorders, including non-neuropathic and neuropathic bladder dysfunctions. The mechanisms of action of the reported techniques remain unclear; urodynamic changes are minimal, but symptomatic improvements are common. Although the treatment is relatively free from side-effects compared with more aggressive surgical options, the placebo effect is likely to be significant. Its exact cost effectiveness is unclear, but the technology is a welcome addition to the range of treatment options for lower urinary tract dysfunctions, such as urgency and urge incontinence.

  9. 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.

  10. Bladder stones after bladder augmentation are not what they seem.

    Science.gov (United States)

    Szymanski, Konrad M; Misseri, Rosalia; Whittam, Benjamin; Lingeman, James E; Amstutz, Sable; Ring, Joshua D; Kaefer, Martin; Rink, Richard C; Cain, Mark P

    2016-04-01

    Bladder and renal calculi after bladder augmentation are thought to be primarily infectious, yet few studies have reported stone composition. The primary aim was to assess bladder stone composition after augmentation, and renal stone composition in those with subsequent nephrolithiasis. The exploratory secondary aim was to screen for possible risk factors for developing infectious stones. Patients treated for bladder stones after bladder augmentation at the present institution between 1981 and 2012 were retrospectively reviewed. Data were collected on demographics, surgeries and stone composition. Patients without stone analysis were excluded. Stones containing struvite, carbonate apatite or ammonium acid ureate were classified as infectious. The following variables were analyzed for a possible association with infectious bladder stone composition: gender, history of cloacal exstrophy, ambulatory status, nephrolithiasis, recurrent urea-splitting urinary tract infections, first vs recurrent stones, timing of presentation with a calculus, history of bladder neck procedures, catheterizable channel and vesicoureteral reflux. Fisher's exact test was used for analysis. Of the 107 patients with bladder stones after bladder augmentation, 85 met inclusion criteria. Median age at augmentation was 8.0 years (follow-up 10.8 years). Forty-four patients (51.8%) recurred (14 multiple recurrences, 143 bladder stones). Renal calculi developed in 19 (22.4%) patients with a bladder stone, and 10 (52.6%) recurred (30 renal stones). Overall, 30.8% of bladder stones were non-infectious (Table). Among patients recurring after an infectious bladder stone, 30.4% recurred with a non-infectious one. Among patients recurring after a non-infectious stone, 84.6% recurred with a non-infectious one (P = 0.005). Compared with bladder stones, renal stones were more likely to be non-infectious (60.0%, P = 0.003). Of patients with recurrent renal calculi after an infectious stone, 40.0% recurred with

  11. The inverse relationship between bladder and liver in 4-aminobiphenyl-induced DNA damage

    Science.gov (United States)

    Stablewski, Aimee B.; Vouros, Paul; Zhang, Yuesheng

    2015-01-01

    Bladder cancer risk is significantly higher in men than in women. 4-Aminobiphenyl (ABP) is a major human bladder carcinogen from tobacco smoke and other sources. In mice, male bladder is more susceptible to ABP-induced carcinogenesis than female bladder, but ABP is more carcinogenic in the livers of female mice than of male mice. Here, we show that castration causes male mice to acquire female phenotype regarding susceptibility of bladder and liver to ABP. However, spaying has little impact on organ susceptibility to ABP. Liver UDP-glucuronosyltransferases (UGTs) are believed to protect liver against but sensitize bladder to ABP, as glucuronidation of ABP and its metabolites generally reduces their toxicity and promotes their elimination via urine, but the metabolites are labile in urine, delivering carcinogenic species to the bladder. Indeed, liver expression of ABP-metabolizing human UGT1A3 transgene in mice increases bladder susceptibility to ABP. However, ABP-specific liver UGT activity is significantly higher in wild-type female mice than in their male counterparts, and castration also significantly increases ABP-specific UGT activity in the liver. Taken together, our data suggest that androgen increases bladder susceptibility to ABP via liver, likely by modulating an ABP-metabolizing liver enzyme, but exclude UGT as an important mediator. PMID:25596734

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

    Directory of Open Access Journals (Sweden)

    Ganglong Yang

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

  13. Sulforaphane induces apoptosis in T24 human urinary bladder cancer cells through a reactive oxygen species-mediated mitochondrial pathway: the involvement of endoplasmic reticulum stress and the Nrf2 signaling pathway.

    Science.gov (United States)

    Jo, Guk Heui; Kim, Gi-Young; Kim, Wun-Jae; Park, Kun Young; Choi, Yung Hyun

    2014-10-01

    Sulforaphane, a naturally occurring isothiocyanate found in cruciferous vegetables, has received a great deal of attention because of its ability to inhibit cell proliferation and induce apoptosis in cancer cells. In this study, we investigated the anticancer activity of sulforaphane in the T24 human bladder cancer line, and explored its molecular mechanism of action. Our results showed that treatment with sulforaphane inhibited cell viability and induced apoptosis in T24 cells in a concentration-dependent manner. Sulforaphane-induced apoptosis was associated with mitochondria dysfunction, cytochrome c release and Bcl-2/Bax dysregulation. Furthermore, the increased activity of caspase-9 and -3, but not caspase-8, was accompanied by the cleavage of poly ADP-ribose polymerase, indicating the involvement of the mitochondria-mediated intrinsic apoptotic pathway. Concomitant with these changes, sulforaphane triggered reactive oxygen species (ROS) generation, which, along with the blockage of sulforaphane-induced loss of mitochondrial membrane potential and apoptosis, was strongly attenuated by the ROS scavenger N-acetyl-L-cysteine. Furthermore, sulforaphane was observed to activate endoplasmic reticulum (ER) stress and the nuclear factor-E2-related factor-2 (Nrf2) signaling pathway, as demonstrated by the upregulation of ER stress‑related proteins, including glucose-regulated protein 78 and C/EBP-homologous protein, and the accumulation of phosphorylated Nrf2 proteins in the nucleus and induction of heme oxygenase-1 expression, respectively. Taken together, these results demonstrate that sulforaphane has antitumor effects against bladder cancer cells through an ROS-mediated intrinsic apoptotic pathway, and suggest that ER stress and Nrf2 may represent strategic targets for sulforaphane-induced apoptosis.

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

    Science.gov (United States)

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

  15. Epidermal growth factor receptor targeting of replication competent adenovirus enhances cytotoxicity in bladder cancer

    NARCIS (Netherlands)

    van der Poel, HG; Molenaar, B; van Beusechem, VW; Haisma, HJ; Rodriguez, R; Curiel, DT; Gerritsen, WR

    Purpose: We evaluated the delivery and oncolytic potential of targeted replication competent adenoviruses in bladder cancer lines. Materials and Methods: Seven established human bladder cancer tumor lines (5637, SW800, TCCsup, J82, Scaber, T24 and 253J) were studied for the expression of integrins

  16. Calcifications of the bladder in schistosomiasis

    International Nuclear Information System (INIS)

    Wechmar, M. von; Vogel, H.

    1989-01-01

    In schistosomiasis calcification of the urinary bladder are characteristic signs that allow a corresponding diagnosis in endemic regions. Problems concerning differential diagnosis occur only in very rare cases. The calcifications of the bladder can be easily detected by native diagnostics. A late complication in an affected bladder is often a bladder carcinoma. (orig.) [de

  17. Confocal Laser Endomicroscopy for the Diagnosis of Urothelial Carcinoma in the Bladder and the Upper Urinary Tract: Protocols for Two Prospective Explorative Studies.

    Science.gov (United States)

    Liem, Esmee Iml; Freund, Jan Erik; Baard, Joyce; de Bruin, D Martijn; Laguna Pes, M Pilar; Savci-Heijink, C Dilara; van Leeuwen, Ton G; de Reijke, Theo M; de la Rosette, Jean Jmch

    2018-02-07

    Visual confirmation of a suspicious lesion in the urinary tract is a major corner stone in diagnosing urothelial carcinoma. However, during cystoscopy (for bladder tumors) and ureterorenoscopy (for tumors of the upper urinary tract) no real-time histopathologic information can be obtained. Confocal laser endomicroscopy (CLE) is an optical imaging technique that allows for in vivo high-resolution imaging and may allow real-time tumor grading of urothelial lesions. The primary objective of both studies is to develop descriptive criteria for in vivo CLE images of urothelial carcinoma (low-grade, high-grade, carcinoma in situ) and normal urothelium by comparing CLE images with corresponding histopathology. In these two prospective clinical trials, CLE imaging will be performed of suspicious lesions and normal tissue in the urinary tract during surgery, prior to resection or biopsy. In the bladder study, CLE will be performed in 60 patients using the Cystoflex UHD-R probe. In the upper urinary tract study, CLE will be performed in 25 patients during ureterorenoscopy, who will undergo radical treatment (nephroureterectomy or segmental ureter resection) thereafter. All CLE images will be analyzed frame by frame by three independent, blinded observers. Histopathology and CLE-based diagnosis of the lesions will be evaluated. Both studies comply with the IDEAL stage 2b recommendations. Presently, recruitment of patients is ongoing in both studies. Results and outcomes are expected in 2018. For development of CLE-based diagnosis of urothelial carcinoma in the bladder and the upper urinary tract, a structured conduct of research is required. This study will provide more insight in tissue-specific CLE criteria for real-time tumor grading of urothelial carcinoma. Confocal Laser Endomicroscopy: ClinicalTrials.gov NCT03013894; https://clinicaltrials.gov /ct2/show/NCT03013894?term=NCT03013894&rank=1 (Archived by WebCite at http://www.webcitation.org/6wiPZ378I); and Dutch Central

  18. An Orthotopic Model of Murine Bladder Cancer

    OpenAIRE

    Dobek, Georgina L.; Godbey, W. T.

    2011-01-01

    In this straightforward procedure, bladder tumors are established in female C57 mice through the use of catheterization, local cauterization, and subsequent cell adhesion. After their bladders are transurethrally catheterized and drained, animals are again catheterized to permit insertion of a platinum wire into bladders without damaging the urethra or bladder. The catheters are made of Teflon to serve as an insulator for the wire, which will conduct electrical current into the bladder to c...

  19. Teardrop bladder: additional considerations

    International Nuclear Information System (INIS)

    Wechsler, R.J.; Brennan, R.E.

    1982-01-01

    Nine cases of teardrop bladder (TDB) seen at excretory urography are presented. In some of these patients, the iliopsoas muscles were at the upper limit of normal in size, and additional evaluation of the perivesical structures with computed tomography (CT) was necessary. CT demonstrated only hypertrophied muscles with or without perivesical fat. The psoas muscles and pelvic width were measured in 8 patients and compared with the measurements of a control group of males without TDB. Patients with TDB had large iliopsoas muscles and narrow pelves compared with the control group. The psoas muscle width/pelvic width ratio was significantly greater (p < 0.0005) in patients with TDB than in the control group, with values of 1.04 + 0.05 and 0.82 + 0.09, respectively. It is concluded that TDB is not an uncommon normal variant in black males. Both iliopsoas muscle hypertrophy and a narrow pelvis are factors that predispose a patient to TDB

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Xu Li-Hua

    2009-02-01

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

  2. Bladder cancer exosomes contain EDIL-3/Del1 and facilitate cancer progression.

    Science.gov (United States)

    Beckham, Carla J; Olsen, Jayme; Yin, Peng-Nien; Wu, Chia-Hao; Ting, Huei-Ju; Hagen, Fred K; Scosyrev, Emelian; Messing, Edward M; Lee, Yi-Fen

    2014-08-01

    High grade bladder cancer is an extremely aggressive malignancy associated with high rates of morbidity and mortality. Understanding how exosomes may affect bladder cancer progression could reveal novel therapeutic targets. Exosomes derived from human bladder cancer cell lines and the urine of patients with high grade bladder cancer were assessed for the ability to promote cancer progression in standard assays. Exosomes purified from the high grade bladder cancer cell line TCC-SUP and the nonmalignant urothelial cell line SV-HUC were submitted for mass spectrometry analysis. EDIL-3 was identified and selected for further analysis. Western blot was done to determine EDIL-3 levels in urinary exosomes from patients with high grade bladder cancer. shRNA gene knockdown and recombinant EDIL-3 were applied to study EDIL-3 function. Exosomes isolated from high grade bladder cancer cells and the urine of patients with high grade bladder cancer promoted angiogenesis and migration of bladder cancer cells and endothelial cells. We silenced EDIL-3 expression and found that shEDIL-3 exosomes did not facilitate angiogenesis, and urothelial and endothelial cell migration. Moreover, exosomes purified from the urine of patients with high grade bladder cancer contained significantly higher EDIL-3 levels than exosomes from the urine of healthy controls. EDIL-3 activated epidermal growth factor receptor signaling while blockade of epidermal growth factor receptor signaling abrogated this EDIL-3 induced bladder cell migration. Exosomes derived from the urine of patients with bladder cancer contains bioactive molecules such as EDIL-3. Identifying these components and their associated oncogenic pathways could lead to novel therapeutic targets and treatment strategies. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  3. Dietary phenolics as anti-mutagens and inhibitors of tobacco-related DNA adduction in the urothelium of smokers.

    Science.gov (United States)

    Malaveille, C; Hautefeuille, A; Pignatelli, B; Talaska, G; Vineis, P; Bartsch, H

    1996-10-01

    Human urine is known to contain substances that strongly inhibit bacterial mutagenicity of aromatic and heterocyclic amines in vitro. The biological relevance of these anti-mutagens was examined by comparing levels of tobacco-related DNA adducts in exfoliated urothelial cells from smokers with the anti-mutagenic activity in corresponding 24-h urine samples. An inverse relationship was found between the inhibition of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-mutagenicity by urine extracts in vitro and two DNA adduct measurements: the level of the putatively identified N-(deoxyguanosine-8-yl)-4-aminobiphenyl adduct and the total level of all tobacco-smoke-related carcinogen adducts including those probably derived from PhIP. Urinary anti-mutagenicity in vitro appears thus to be a good indicator of the anti-genotoxicity exerted by substances excreted in urine, that protect the bladder mucosal cells (and possibly other cells) against DNA damage. These substances appear to be dietary phenolics and/or their metabolites because (i) the anti-mutagenic activity of urine extracts (n = 18) was linearly related to their content in phenolics; (ii) the concentration ranges of these substances in urine extracts were similar to those of various plant phenols (quercetin, isorhamnetin and naringenin) for which an inhibitory effect on the liver S9-mediated mutagenicity of PhIP was obtained; (iii) treatment of urines with beta-glucuronidase and arylsulfatase enhanced both anti-mutagenicity and the levels of phenolics in urinary extracts; (iv) urinary extracts inhibited noncompetitively the liver S9-mediated mutagenicity of PhIP as did quercetin, used as a model phenolics. Several structural features of the flavonoids were identified as necessary for the inhibition of PhIP and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxiline mutagenicity. Fractionation by reverse-phase HPLC and subsequent analysis of two urinary extracts, showed the presence of several anti

  4. Immunolocalisation of oestrogen receptor beta in human tissues.

    Science.gov (United States)

    Taylor, A H; Al-Azzawi, F

    2000-02-01

    Oestrogens exert their actions via specific nuclear protein receptors that are members of the steroid/thyroid receptor superfamily of transcription factors. Recently, a second oestrogen receptor (ERbeta) has been cloned, and using reverse transcription-PCR and immunohistochemistry it has been shown to have a wide tissue distribution in the rat that is distinct from the classical oestrogen receptor, ERalpha. Using commercial polyclonal antisera against peptides specific to human ERbeta, we have determined the sites of ERbeta expression in archival and formalin-fixed human tissue and compared its expression with that of ERalpha. ERbeta was localised to the cell nuclei of a wide range of normal adult human tissues including ovary, Fallopian tube, uterus, lung, kidney, brain, heart, prostate and testis. In the ovary, ERbeta was present in multiple cell types including granulosa cells in small, medium and large follicles, theca and corpora lutea, whereas ERalpha was weakly expressed in the nuclei of granulosa cells, but not in the theca nor in the copora lutea. In the endometrium, both ERalpha and ERbeta were observed in luminal epithelial cells and in the nuclei of stromal cells but, significantly, ERbeta was weak or absent from endometrial glandular epithelia. Epithelial cells in most male tissues including the prostate, the urothelium and muscle layers of the bladder, and Sertoli cells in the testis, were also immunopositive for ERbeta. Significant ERbeta immunoreactivity was detected in most areas of the brain, with the exception of the hippocampus - a tissue that stained positively for ERalpha. In conclusion, the almost ubiquitous immunohistochemical localisation of ERbeta indicates that ERbeta may play a major role in the mediation of oestrogen action. The differential expression of ERalpha and ERbeta in some of these tissues suggests a more complex control mechanism in oestrogenic potential than originally envisioned.

  5. Treatment Option Overview (Bladder Cancer)

    Science.gov (United States)

    ... above the waist. Tiny tubules in the kidneys filter and clean the blood . They take out waste ... to bladder cancer. Being exposed to paints, dyes, metals, or petroleum products in the workplace. Past treatment ...

  6. Drugs Approved for Bladder Cancer

    Science.gov (United States)

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

  7. Neurogenic bladder in Hunter's syndrome.

    Science.gov (United States)

    Koyama, K; Moda, Y; Sone, A; Tanaka, H; Hino, Y

    1994-01-01

    We encountered a rare patient with Hunter's syndrome who exhibited urinary retention as a result of a neurogenic bladder, uninhibited detrusor contractions, and detrusor-sphincter dyssynergia. Neurological findings were consistent with cervical myelopathy and cervical MR imaging showed very narrow segments at the cord level C2-4. We speculate that this Hunter's syndrome patient has cervical myelopathy and that this neurological dysfunction causes the neurogenic bladder. PMID:8014981

  8. Constructive remodeling of biologic scaffolds is dependent on early exposure to physiologic bladder filling in a canine partial cystectomy model.

    Science.gov (United States)

    Boruch, Alan V; Nieponice, Alejandro; Qureshi, Irfan R; Gilbert, Thomas W; Badylak, Stephen F

    2010-06-15

    Biologic scaffolds composed of extracellular matrix (ECM) have been used to facilitate the constructive remodeling of several tissue types. Previous studies suggest that the ECM scaffold remodeling process is dependent on microenvironmental factors, including tissue-specific biomechanical loading. The objective of the present study was to evaluate the effects of long-term catheterization (LTC), with its associated inhibition of bladder filling and physiologic biomechanical loading, on ECM scaffold remodeling following partial cystectomy in a canine model. Reconstruction of the partial cystectomy site was performed using ECM scaffolds prepared from porcine small intestinal submucosa (SIS) or porcine urinary bladder matrix (UBM). Animals were randomly assigned to either a long-term catheterization (LTC) group (n=5, catheterized 28 d) or a short-term catheterization group (STC, n=5, catheterized 24 h), and scaffold remodeling was assessed by histologic methods at 4 and 12 wk postoperatively. By 4 wk, animals in the STC group showed a well-developed and highly differentiated urothelium, a robust vascularization network, abundant smooth muscle actin (SMA), and smooth muscle myosin heavy chain (smMHC) expressing spindle-shaped cells, and many neuronal processes associated with newly formed arterioles. In contrast, at 4 wk the scaffolds in LTC animals were not epithelialized, and did not express neuronal markers. The scaffolds in the LTC group developed a dense granulation tissue containing SMA+, smMHC-, spindle-shaped cells that were morphologically and phenotypically consistent with myofibroblasts, but not smooth muscle cells. By 12 wk postoperatively, the ECM scaffolds in the STC animals showed a constructive remodeling response, with a differentiated urothelium and islands of smooth muscle cells within the remodeled scaffold. In contrast, at 12 wk the scaffolds in LTC animals had a remodeling response more consistent with fibrosis even though catheters had been

  9. Interstitial cystitis: painful bladder syndrome

    Directory of Open Access Journals (Sweden)

    R F Sholan

    2018-02-01

    Full Text Available Interstitial cystitis, or painful bladder syndrome, is a chronic inflammatory disease of a bladder of unknown etiology. It negatively affects the quality of life, causes depressive disorders, anxiety, and sexual dysfunction. Despite numerous studies, the etiology of interstitial cystitis is still unclear and it’s considered as painful bladder syndrome with multifactorial origin. According to the US National Health and Nutrition Examination Survey, 470/100 000 people (60/100 000 men, 850/100 000 women are diagnosed with interstitial cystitis. Diagnosis of the disease is difficult and is substantially based on clinical symptoms. Pelvic pain, urinary urgency, frequency and nocturia are the basic complaints in this pathology. The diagnosis requires exclusion of diseases with similar manifestations. So interstitial cystitis is frequently misdiagnosed as urinary tract infection, overactive bladder, urethral obstruction or diverticulosis, chronic prostatitis, bladder cancer, vulvodynia, endometriosis, and chronic pelvic pain. Etiopathogenesis of the disease is uncertain, which makes etiologic treatment impossible. Currently scientific discussions on the causes of disease continue as well as different treatment regimens are offered, but are often ineffective, palliative and temporary. The treatment for intersticial cystitis should focus on restoring normal bladder function, prevention of relapse of symptoms and improvement of patients’ quality of life. The literature review presents current view on the terminology, epidemiology, diagnosis and treatment of interstitial cystitis.

  10. Current management of overactive bladder.

    Science.gov (United States)

    Cartwright, Rufus; Renganathan, Arasee; Cardozo, Linda

    2008-10-01

    The concept of overactive bladder has helped us address the problem of urgency and urge incontinence from a symptomatic perspective. In this review, we provide a critical summary of clinically relevant recent publications, focusing in particular on advances in our understanding of assessment methods and therapeutic interventions for overactive bladder in women. According to current definitions, the prevalence of overactive bladder in western nations is now estimated as 13.0%. Although the prevalence increases with age, the symptoms of overactive bladder may follow a relapsing and remitting course. There has been a proliferation of validated symptom and quality of life measures and increasing sophistication in the analysis of bladder diaries. The role of urodynamics in the evaluation of urgency remains uncertain, with many trials showing limited benefit as a preoperative investigation. Fluid restriction and bladder retraining remain important first-line interventions. Many new anticholinergic medications have been licensed, with limited benefits compared with existing preparations. Intravesical botulinum toxin has become a popular alternative for patients who fail oral therapies. Although there have been few important therapeutic innovations, recent publications have led to greater sophistication in assessment methods and a clearer understanding of the role of existing interventions.

  11. Bladder Dysfunction and Vesicoureteral Reflux

    Directory of Open Access Journals (Sweden)

    Ulla Sillén

    2008-01-01

    Full Text Available In this overview the influence of functional bladder disturbances and of its treatment on the resolution of vesicoureteral reflux (VUR in children is discussed. Historically both bladder dysfunction entities, the overactive bladder (OAB and the dysfunctional voiding (DV, have been described in conjunction with VUR. Treatment of the dysfunction was also considered to influence spontaneous resolution in a positive way. During the last decades, however, papers have been published which could not support these results. Regarding the OAB, a prospective study with treatment of the bladder overactivity with anticholinergics, did not influence spontaneous resolution rate in children with a dysfunction including also the voiding phase, DV and DES (dysfunctional elimination syndrome, most studies indicate a negative influence on the resolution rate of VUR in children, both before and after the age for bladder control, both with and without treatment. However, a couple of uncontrolled studies indicate that there is a high short-term resolution rate after treatment with flow biofeedback. It should be emphasized that the voiding phase dysfunctions (DV and DES are more severe than the genuine filling phase dysfunction (OAB, with an increased frequency of UTI and renal damage in the former groups. To be able to answer the question if treatment of bladder dysfunction influence the resolution rate of VUR in children, randomized controlled studies must be performed.

  12. Preliminary results of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced or metastatic transitional cell carcinoma of the urothelium.

    Science.gov (United States)

    Yamada, Yoshiaki; Itoh, Youko; Aoki, Shigeyuki; Nakamura, Kogenta; Taki, Tomohiro; Naruse, Katsuya; Tobiume, Motoi; Zennami, Kenji; Katsuda, Remi; Kato, Yoshiharu; Watanabe, Masahito; Nishikawa, Genya; Minami, Miwako; Nakahira, Mariko; Ukai, Sayaka; Sawada, Masaki; Kitamura, Akiko; Honda, Nobuaki

    2009-11-01

    We evaluated the efficacy and safety of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced metastatic transitional cell carcinoma of the urothelium. The subjects were 12 patients diagnosed with advanced metastatic transitional cell carcinoma of the urothelium. For mild hyperthermia, the patients' oral temperature was elevated to about 38 degrees C by heating for 20 min and retaining the heat for 20 min with a far-infrared heater. The antitumor effect was evaluated according to the RECIST, while adverse drug reactions were assessed based on the NCI-CTC. The antitumor effect was rated as partial remission (PR) in 10 of the 12 patients and stable disease in 2 patients, with an efficacy rate of 83% (10/12). All 10 patients who had achieved PR received three courses of treatment. Of the 12 patients, 5 died during the observation period, with survival for 9-23 months (mean: 15.6 months). Adverse drug reactions included myelosuppression in all patients (Grade 3 in 4 patients, Grade 4 in 8), and gastrointestinal toxicity, such as nausea or vomiting, which was mild (Grade 0 in 2 patients, Grade 1 in 8, Grade 2 in 1, Grade 3 in 1). The results of the present study suggest that M-VAC chemotherapy combined with mild hyperthermia, which potentiates the anticancer effect and reduces adverse drug reactions such as gastrointestinal symptoms, is a useful and safe method for the treatment of advanced transitional cell carcinoma of the urothelium.

  13. Positive Correlation between Matrix Metalloproteinases and Epithelial-to-Mesenchymal Transition and its Association with Clinical Outcome in Bladder Cancer Patients.

    Science.gov (United States)

    Singh, R; Mandhani, A; Agrawal, V; Garg, Minal

    2018-01-18

    Involvement of matrix metalloproteinases (MMPs) in the pathogenesis of urothelial carcinoma elects them to be sensitive marker for clinical and prognostic implications. MMPs regulate tumor growth and invasion by inducing epithelial-to-mesenchymal transition (EMT) which is characterized by the complex reprogramming of epithelial cells and ultimately bring about major changes in the structural organization of bladder urothelium. The present study has been undertaken to evaluate the clinical relevance of MMPs in two distinct types of bladder cancer disease. Expression analysis of MMPs namely MMP-2, MMP-7, MMP-9 and EMT markers including epithelial marker, E-cadherin; mesenchymal markers, N-cadherin and Vimentin; and EMT-activating transcriptional factors (EMT-ATFs), Snail, Slug, Twist and Zeb was done in 64 cases of bladder tumor tissues [{Non-muscle invasive bladder cancer (NMIBC): 35 cases} and {Muscle invasive bladder cancer (MIBC): 29 cases}] by real-time quantitative polymerase chain reaction (RT-qPCR). Immunohistochemistry (IHC) staining was done in matched bladder tumor tissues to evaluate the protein expression and localization of E-cadherin, N-cadherin, Vimentin, Snail, and Slug. Our data showed overexpression of MMP-2, MMP-7 and MMP-9 at transcriptome level in 32.8%, 25% and 37.5% bladder tumor cases respectively. These tumor tissues were examined for higher expression of mesenchymal markers (N-cadherin and Vimentin) at mRNA and protein level and exhibited statistical association with tumor stage and tumor grade (p = 0.02, p = 0.04, Mann-Whitney test). Significant statistical correlation in tumor tissues with overexpressed MMPs has also been observed between gain of transcriptional factors and weak expression of E-cadherin with tumor stage, grade, gender, presence of hematuria and smoking history of the patients. Gene expression patterns of EMT markers in bladder tumors with overexpressed MMPs and their significant association with clinical profile

  14. Analysis of Clinicopathological Features and Prognostic Factors in 39 Cases of Bladder Neuroendocrine Carcinoma.

    Science.gov (United States)

    Zhou, Hui-Hui; Liu, Li-Yan; Yu, Guo-Hua; Qu, Gui-Mei; Gong, Pei-You; Yu, Xiao; Yang, Ping

    2017-08-01

    Through analysis and summarization of clinicopathological features, immunohistochemical expression, pathological diagnostic criteria, prognostic and other factors in patients suffering from bladder neuroendocrine carcinoma (BNEC), a better understanding of BNEC could be achieved to provide solid evidence for clinicopathology and prognosis. The clinicopathological data of 39 cases of BNEC with up to 5-year follow-up data (median follow-up=650 days) were analyzed retrospectively based on immunohistochemical staining. Survival analyses were carried out using the Kaplan-Meier method and tested with the log-rank method. Multivariate Cox regression analysis was adopted to screen independent risk factors affecting patients' survival. In these 39 cases of BNEC, there were 26 cases of male patients, 13 female, with the proportion of male to female being 2:1. The ages of onset ranged from 44 to 86, with the median age being 62 and the average age 61.97 years, respectively. Histologically, referring to the WHO standard of neuroendocrine lung tumor classification, there were 7 cases of typical carcinoid tumors, 8 atypical carcinoid, 12 small-cell carcinomas and 12 large-cell carcinomas. In these cases there were 11 cases of featured urothelium carcinomas and 9 cases of adenocarcinomas. Immunohistochemical staining showed that, in these 39 cases of BNEC, the positive expression for the neuroendocrinic markers, including neural cell adhesion molecule 56 (CD56), synaptophysin (Syn), chromogranin A (CgA), neuron-specific enolase (NSE), thyroid transcription factor-1 (TTF-1), cytokeratin (CK) and cytokeratin 7 (CK7), accounted for 39/39, 27/39, 18/39, 39/39, 19/39, 10/39 and 8/39, respectively. In contrast, cytokeratin 20 (CK20), protein 63 (P63), human melanoma black 45 (HMB45), S-lfln protein 100 (S-100) and leukocyte common antigen (LCA) were all negatively expressed. During the follow-up period, 12 patients died. The 1-, 3- and 5-year overall survival (OS) rates were 76.92%, 74

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

    International Nuclear Information System (INIS)

    Abe, Toyofumi; Yoshioka, Toshiaki; Sato, Mototaka; Mori, Naoki; Sekii, Ken-Ichiro; Itatani, Hiroaki

    2011-01-01

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

  16. Severe systemic toxicity and urinary bladder cytotoxicity and regenerative hyperplasia induced by arsenite in arsenic (+ 3 oxidation state) methyltransferase knockout mice. A preliminary report

    International Nuclear Information System (INIS)

    Yokohira, Masanao; Arnold, Lora L.; Pennington, Karen L.; Suzuki, Shugo; Kakiuchi-Kiyota, Satoko; Herbin-Davis, Karen; Thomas, David J.; Cohen, Samuel M.

    2010-01-01

    Arsenic (+ 3 oxidation state) methyltransferase (As3mt) catalyzes reactions which convert inorganic arsenic to methylated metabolites. This study determined whether the As3mt null genotype in the mouse modifies cytotoxic and proliferative effects seen in urinary bladders of wild type mice after exposure to inorganic arsenic. Female wild type C57BL/6 mice and As3mt KO mice were divided into 3 groups each (n = 8) with free access to a diet containing 0, 100 or 150 ppm of arsenic as arsenite (As III ). During the first week of As III exposure, As3mt KO mice exhibited severe and lethal systemic toxicity. At termination, urinary bladders of both As3mt KO and wild type mice showed hyperplasia by light microscopy. As expected, arsenic-containing granules were found in the superficial urothelial layer of wild type mice. In As3mt KO mice these granules were present in all layers of the bladder epithelium and were more abundant and larger than in wild type mice. Scanning electron microscopy of the bladder urothelium of As3mt KO mice treated with 100 ppm As III showed extensive superficial necrosis and hyperplastic changes. In As3mt KO mice, livers showed severe acute inflammatory changes and spleen size and lymphoid areas were decreased compared with wild type mice. Thus, diminished arsenic methylation in As3mt KO mice exacerbates systemic toxicity and the effects of As III on the bladder epithelium, showing that altered kinetic and dynamic behavior of arsenic can affect its toxicity.

  17. Interstitial cystitis/bladder pain syndrome: diagnosis and management.

    Science.gov (United States)

    Offiah, I; McMahon, S B; O'Reilly, B A

    2013-08-01

    The bladder pain syndrome (BPS) is a spectrum of urological symptoms characterised by bladder pain with typical cystoscopic features. Diagnosis and management of this syndrome may be difficult. There is no evidence-based management approach for the diagnosis or treatment of BPS. The objective of this study was to critically review and summarise the evidence relating to the diagnosis and treatment of the bladder pain syndrome. A review of published data on the diagnosis and treatment of the BPS was performed. Our search was limited to English-language articles, on the "diagnosis", and "management" or "treatment" of "interstitial cystitis" and the "bladder pain syndrome" in "humans." Frequency, urgency and pain on bladder filling are the most common symptoms of BPS. All urodynamic volumes are reduced in patients with BPS. Associated conditions include psychological distress, depression, history of sexual assault, irritable bowel syndrome and fibromyalgia. Cystoscopy remains the test for definitive diagnosis, with visualisation of haemorrhage on cystoreduction. A multidisciplinary treatment approach is essential in the management of this condition. Orally administered amitriptyline is an efficacious medical treatment for BPS. Intravesical hyaluronic acid and local anaesthetic, with/without hydrodistension are among new treatment strategies. Sacral or pudendal neuromodulation is effective, minimally invasive and safe. Surgery is reserved for refractory cases. There remains a paucity of evidence for the diagnosis and treatment of BPS. We encountered significant heterogeneity in the assessment of symptoms, duration of treatment and follow up of patients in our literature review.

  18. Bladder wall thickness mapping for magnetic resonance cystography

    International Nuclear Information System (INIS)

    Zhao Yang; Liang Zhengrong; Zhu Hongbin; Han Hao; Yan Zengmin; Duan Chaijie; Lu Hongbing; Gu Xianfeng

    2013-01-01

    Clinical studies have shown evidence that the bladder wall thickness is an effective biomarker for bladder abnormalities. Clinical optical cystoscopy, the current gold standard, cannot show the wall thickness. The use of ultrasound by experts may generate some local thickness information, but the information is limited in field-of-view and is user dependent. Recent advances in magnetic resonance (MR) imaging technologies lead MR-based virtual cystoscopy or MR cystography toward a potential alternative to map the wall thickness for the entire bladder. From a high-resolution structural MR volumetric image of the abdomen, a reasonable segmentation of the inner and outer borders of the bladder wall can be achievable. Starting from here, this paper reviews the limitation of a previous distance field-based approach of measuring the thickness between the two borders and then provides a solution to overcome the limitation by an electric field-based strategy. In addition, this paper further investigates a surface-fitting strategy to minimize the discretization errors on the voxel-like borders and facilitate the thickness mapping on the three-dimensional patient-specific bladder model. The presented thickness calculation and mapping were tested on both phantom and human subject datasets. The results are preliminary but very promising with a noticeable improvement over the previous distance field-based approach. (paper)

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

    Directory of Open Access Journals (Sweden)

    Leifheit Erica C

    2004-07-01

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

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

    International Nuclear Information System (INIS)

    Meyer-Siegler, Katherine L; Leifheit, Erica C; Vera, Pedro L

    2004-01-01

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

  1. De novo reconstitution of a functional mammalian urinary bladder by tissue engineering.

    Science.gov (United States)

    Oberpenning, F; Meng, J; Yoo, J J; Atala, A

    1999-02-01

    Human organ replacement is limited by a donor shortage, problems with tissue compatibility, and rejection. Creation of an organ with autologous tissue would be advantageous. In this study, transplantable urinary bladder neo-organs were reproducibly created in vitro from urothelial and smooth muscle cells grown in culture from canine native bladder biopsies and seeded onto preformed bladder-shaped polymers. The native bladders were subsequently excised from canine donors and replaced with the tissue-engineered neo-organs. In functional evaluations for up to 11 months, the bladder neo-organs demonstrated a normal capacity to retain urine, normal elastic properties, and histologic architecture. This study demonstrates, for the first time, that successful reconstitution of an autonomous hollow organ is possible using tissue-engineering methods.

  2. Medical management of overactive bladder

    Directory of Open Access Journals (Sweden)

    Sarvpreet S Ubee

    2010-01-01

    Full Text Available Overactive bladder (OAB, as defined by the International Continence Society, is characterized by a symptom complex including urinary urgency with or without urge incontinence, usually associated with frequency and nocturia. OAB syndrome has an incidence reported from six European countries ranging between 12-17%, while in the United States; a study conducted by the National Overactive Bladder Evaluation program found the incidence at 17%. In Asia, the prevalence of OAB is reported at 53.1%. In about 75%, OAB symptoms are due to idiopathic detrusor activity; neurological disease, bladder outflow obstruction (BOO intrinsic bladder pathology and other chronic pelvic floor disorders are implicated in the others. OAB can be diagnosed easily and managed effectively with both non-pharmacological and pharmacological therapies. The first-line treatments are lifestyle interventions, bladder training, pelvic floor muscle exercises and anticholinergic drugs. Antimuscarinics are the drug class of choice for OAB symptoms; with proven efficacy, and adverse event profiles that differ somewhat.

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

    Directory of Open Access Journals (Sweden)

    Letašiová Silvia

    2012-06-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

    In multiple plan adaptive radiotherapy (ART) strategies of bladder cancer, a library of plans corresponding to different bladder volumes is created based on images acquired in early treatment sessions. Subsequently, the plan for the smallest PTV safely covering the bladder on cone-beam CT (CBCT) is

  5. Long non-coding RNA ANRIL is up-regulated in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic pathway

    International Nuclear Information System (INIS)

    Zhu, Hongxue; Li, Xuechao; Song, Yarong; Zhang, Peng; Xiao, Yajun; Xing, Yifei

    2015-01-01

    Antisense non-coding RNA in the INK4 locus (ANRIL) is a member of long non-coding RNAs and has been reported to be dysregulated in several human cancers. However, the role of ANRIL in bladder cancer remains unclear. This present study aimed to investigate whether and how ANRIL involved in bladder cancer. Our results showed up-regulation of ANRIL in bladder cancer tissues versus the corresponding adjacent non-tumor tissues. To explore the specific mechanisms, ANRIL was silenced by small interfering RNA or short hairpin RNA transfection in human bladder cancer T24 and EJ cells. Knockdown of ANRIL repressed cell proliferation and increased cell apoptosis, along with decreased expression of Bcl-2 and increased expressions of Bax, cytoplasmic cytochrome c and Smac and cleaved caspase-9, caspase-3 and PARP. However, no change of cleaved caspase-8 level was observed. Furthermore, in vivo experiment confirmed that knockdown of ANRIL inhibited tumorigenic ability of EJ cells in nude mice. Meanwhile, in accordance with in vitro study, knockdown of ANRIL inhibited expression of Bcl-2 and up-regulated expressions of Bax and cleaved caspase-9, but did not affect cleaved caspase-8 level. In conclusion, we first report that ANRIL possibly serves as an oncogene in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic apoptosis pathway. - Highlights: • We first report the role of ANRIL in bladder cancer. • ANRIL is obviously up-regulated in bladder cancer tissues. • ANRIL regulates bladder cancer cell proliferation and cell apoptosis through the intrinsic pathway.

  6. Fundamentals of bladder tissue engineering | Mahfouz | African ...

    African Journals Online (AJOL)

    Fundamentals of bladder tissue engineering. ... could affect the bladder and lead to eventual loss of its integrity, with the need for replacement or repair. ... Tissue engineering relies upon three essential pillars; the scaffold, the cells seeded on ...

  7. Aging changes in the kidneys and bladder

    Science.gov (United States)

    ... affect kidney function. COMMON PROBLEMS Aging increases the risk of kidney and bladder problems such as: Bladder control issues, such as leakage or urinary incontinence (not being able to hold your urine), or ...

  8. An orthotopic model of murine bladder cancer.

    Science.gov (United States)

    Dobek, Georgina L; Godbey, W T

    2011-02-06

    In this straightforward procedure, bladder tumors are established in female C57 mice through the use of catheterization, local cauterization, and subsequent cell adhesion. After their bladders are transurethrally catheterized and drained, animals are again catheterized to permit insertion of a platinum wire into bladders without damaging the urethra or bladder. The catheters are made of Teflon to serve as an insulator for the wire, which will conduct electrical current into the bladder to create a burn injury. An electrocautery unit is used to deliver 2.5W to the exposed end of the wire, burning away extracellular layers and providing attachment sites for carcinoma cells that are delivered in suspension to the bladder through a subsequent catheterization. Cells remain in the bladder for 90 minutes, after which the catheters are removed and the bladders allowed to drain naturally. The development of tumor is monitored via ultrasound. Specific attention is paid to the catheterization technique in the accompanying video.

  9. Toll-Like Receptor 4 Activation Contributes to Diabetic Bladder Dysfunction in a Murine Model of Type 1 Diabetes.

    Science.gov (United States)

    Szasz, Theodora; Wenceslau, Camilla F; Burgess, Beth; Nunes, Kenia P; Webb, R Clinton

    2016-12-01

    Diabetic bladder dysfunction (DBD) is a common urological complication of diabetes. Innate immune system activation via Toll-like receptor 4 (TLR4) leads to inflammation and oxidative stress and was implicated in diabetes pathophysiology. We hypothesized that bladder hypertrophy and hypercontractility in DBD is mediated by TLR4 activation. Wild-type (WT) and TLR4 knockout (TLR4KO) mice were made diabetic by streptozotocin (STZ) treatment, and bladder contractile function and TLR4 pathway expression were evaluated. Immunohistochemistry confirmed the expression of TLR4 in human and mouse bladder. Recombinant high-mobility group box protein 1 (HMGB1) increased bladder TLR4 and MyD88 expression and enhanced contractile response to electrical field stimulation. Bladder expression of TLR4 and MyD88 and serum expression of HMGB1 were increased in STZ compared with control mice. Carbachol (CCh)-mediated contraction was increased in bladders from STZ mice, and TLR4 inhibitor CLI-095 attenuated this increase. Induction of diabetes by STZ in WT mice increased bladder weight and contractile responses to CCh and to electrical field stimulation. TLR4KO mice were not protected from STZ-induced diabetes; however, despite levels of hyperglycemia similar to those of WT STZ mice, TLR4KO STZ mice were protected from diabetes-induced bladder hypertrophy and hypercontractility. These data suggest that TLR4 activation during diabetes mediates DBD-associated bladder hypertrophy and hypercontractility. © 2016 by the American Diabetes Association.

  10. Initiation of bladder voiding with epidural stimulation in paralyzed, step trained rats.

    Science.gov (United States)

    Gad, Parag N; Roy, Roland R; Zhong, Hui; Lu, Daniel C; Gerasimenko, Yury P; Edgerton, V Reggie

    2014-01-01

    The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury.

  11. Initiation of bladder voiding with epidural stimulation in paralyzed, step trained rats.

    Directory of Open Access Journals (Sweden)

    Parag N Gad

    Full Text Available The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury.

  12. [Occupational hazards and bladder cancer].

    Science.gov (United States)

    Nizamova, R S

    1991-01-01

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

  13. Tumour cell expansion in bladder epithelium

    NARCIS (Netherlands)

    J.M.J. Rebel (Annemarie)

    1995-01-01

    textabstractBladder cancer is common in western society. The major problem of patients with superficial bladder cancer is the high recurrence rate and multifocality of these tumours. In 70 % of the patients superficial bladder cancer recurs after local resection of the tumour within 15 years. The

  14. Bladder Cancer—Health Professional Version

    Science.gov (United States)

    Transitional cell carcinoma of the bladder can be low-grade or high-grade. Bladder cancer is also divided into muscle-invasive and nonmuscle-invasive disease. Find evidence-based information on bladder cancer including treatment, screening, research, and statistics.

  15. Bladder Dysfunction and Urinary Incontinence

    OpenAIRE

    F. faizi

    2009-01-01

      "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 ...

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

    International Nuclear Information System (INIS)

    Qin, Zi-Ke; Zeng, Mu-Sheng; Yang, Jian-An; Ye, Yun-lin; Zhang, Xing; Xu, Li-Hua; Zhou, Fang-Jian; Han, Hui; Liu, Zuo-Wei; Song, Li-Bing

    2009-01-01

    The molecular mechanisms of the development and progression of bladder cancer are poorly understood. The objective of this study was to analyze the expression of Bmi-1 protein and its clinical significance in human bladder cancer. We examined the expression of Bmi-1 mRNA and Bmi-1 protein by RT-PCR and Western blot, respectively in 14 paired bladder cancers and the adjacent normal tissues. The expression of Bmi-1 protein in 137 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between expression of Bmi-1, and clinicopathologic features and prognosis. Expression of Bmi-1 mRNA and protein was higher in bladder cancers than in the adjacent normal tissues in 14 paired samples (P < 0.01). By immunohistochemical examination, five of 30 adjacent normal bladder specimens (16.7%) versus 75 of 137 bladder cancers (54.3%) showed Bmi-1 protein expression (P < 0.05). Bmi-1 protein expression was intense in 20.6%, 54.3%, and 78.8% of tumors of histopathological stages G1, G2, and G3, respectively (P < 0.05). Expression of Bmi-1 protein was greater in invasive bladder cancers than in superficial bladder cancers (81.5% versus 32.5%, P < 0.05). In invasive bladder cancers, the expression of Bmi-1 protein in progression-free cancers was similar to that of cancers that have progressed (80.0% versus 82.4%, P > 0.5). In superficial bladder cancers, the expression of Bmi-1 protein in recurrent cases was higher than in recurrence-free cases (62.5% versus 13.7%, P < 0.05). Bmi-1 expression was positively correlated with tumor classification and TNM stage (P < 0.05), but not with tumor number (P > 0.05). Five-year survival in the group with higher Bmi-1 expression was 50.8%, while it was 78.5% in the group with lower Bmi-1 expression (P < 0.05). Patients with higher Bmi-1 expression had shorter survival time, whereas patients with lower Bmi-1 expression had longer

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

    Directory of Open Access Journals (Sweden)

    Goldberg José

    2008-08-01

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

  18. Bladder Cancer Risk Prediction Models

    Science.gov (United States)

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

  19. Bladder-type hydropneumatic accumulators

    International Nuclear Information System (INIS)

    Anigas, F.

    1985-01-01

    Hydropneumatic pressure accumulators allow liquids to be stored under pressure, their operating principle being based on the inherent compressibility of elements in a liquid and gaseous state. A wide range of fluids can be covered by means of the appropriate choice of the material for the body and bladder. Their main applications are: energy accumulation, safety reserve, suspension. (author)

  20. Bladder carcinoma. Apport MR imaging

    International Nuclear Information System (INIS)

    Roy, C.; Spittler, G.; Jacqmin, D.; Morel, M.

    1991-01-01

    Bladder carcinoma is the second most commun cause of urogenital tumor. It is suspected by abdominal ultrasound and prouved by cystoscopy with biopsy. At present, MR Imaging is the most accurate diagnostic modality for loco-regional staging. Urography is still useful to appreciate urinary tract [fr

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Leiomyoma of the bladder and MRI

    International Nuclear Information System (INIS)

    Kabbaj, N.; Dafiri, R.; Imani, F.; Benslimane, L.; Benchekroun, A.

    1998-01-01

    Unlike epithelial tumors, connective tissue tumors are uncommon, representing only 3 % of all bladder tumors. Leiomyoma of the bladder is the most frequent non-epithelial benign tumor of the bladder. Magnetic resonance imaging (MIR) is highly useful for diagnostic purposes and to determine the degree of extension. Only few reports of sonographic findings have been reported for leiomyoma of the bladder. The tumor usually develops within the bladder. Extra-vesicular formations have also been reported as well as a few intramural localizations. The characteristic feature is the absence of mucosal involvement. We analyzed the MRI findings in a case of leiomyoma of the bladder with intra and extra-vesicular development inflammatory reaction of the bladder wall and uterine adherences in a woman with a past history of chronic cystitis. The role of diagnostic MRI is discussed. (author)

  3. Pathobiology and Chemoprevention of Bladder Cancer

    Science.gov (United States)

    Tanaka, Takuji; Miyazawa, Katsuhito; Tsukamoto, Tetsuya; Kuno, Toshiya; Suzuki, Koji

    2011-01-01

    Our understanding of the pathogenesis of bladder cancer has improved considerably over the past decade. Translating these novel pathobiological discoveries into therapies, prevention, or strategies to manage patients who are suspected to have or who have been diagnosed with bladder cancer is the ultimate goal. In particular, the chemoprevention of bladder cancer development is important, since urothelial cancer frequently recurs, even if the primary cancer is completely removed. The numerous alterations of both oncogenes and tumor suppressor genes that have been implicated in bladder carcinogenesis represent novel targets for therapy and prevention. In addition, knowledge about these genetic alterations will help provide a better understanding of the biological significance of preneoplastic lesions of bladder cancer. Animal models for investigating bladder cancer development and prevention can also be developed based on these alterations. This paper summarizes the results of recent preclinical and clinical chemoprevention studies and discusses screening for bladder cancer. PMID:21941546

  4. Simulated physiological stretch increases expression of extracellular matrix proteins in human bladder smooth muscle cells via integrin α4/αv-FAK-ERK1/2 signaling pathway.

    Science.gov (United States)

    Chen, Shulian; Peng, Chuandu; Wei, Xin; Luo, Deyi; Lin, Yifei; Yang, Tongxin; Jin, Xi; Gong, Lina; Li, Hong; Wang, Kunjie

    2017-08-01

    To investigate the effect of simulated physiological stretch on the expression of extracellular matrix (ECM) proteins and the role of integrin α4/αv, focal adhesion kinase (FAK), extracellular regulated protein kinases 1/2 (ERK1/2) in the stretch-induced ECM protein expression of human bladder smooth muscle cells (HBSMCs). HBSMCs were seeded onto silicone membrane and subjected to simulated physiological stretch at the range of 5, 10, and 15% elongation. Expression of primary ECM proteins in HBSMCs was analyzed by real-time polymerase chain reaction and Western blot. Specificity of the FAK and ERK1/2 was determined by Western blot with FAK inhibitor and ERK1/2 inhibitor (PD98059). Specificity of integrin α4 and integrin αv was determined with small interfering ribonucleic acid (siRNA) transfection. The expression of collagen I (Col1), collagen III (Col3), and fibronectin (Fn) was increased significantly under the simulated physiological stretch of 10 and 15%. Integrin α4 and αv, FAK, ERK1/2 were activated by 10% simulated physiological stretch compared with the static condition. Pretreatment of ERK1/2 inhibitor, FAK inhibitor, integrin α4 siRNA, or integrin αv siRNA reduced the stretch-induced expression of ECM proteins. And FAK inhibitor decreased the stretch-induced ERK1/2 activity and ECM protein expression. Integrin α4 siRNA or integrin αv siRNA inhibited the stretch-induced activity of FAK. Simulated physiological stretch increases the expression of ECM proteins in HBSMCs, and integrin α4/αv-FAK-ERK1/2 signaling pathway partly modulates the mechano-transducing process.

  5. Infiltrating T Cells Promote Bladder Cancer Progression via Increasing IL1→Androgen Receptor→HIF1α→VEGFa Signals.

    Science.gov (United States)

    Tao, Le; Qiu, Jianxin; Jiang, Ming; Song, Wenbin; Yeh, Shuyuan; Yu, Hong; Zang, Lijuan; Xia, Shujie; Chang, Chawnshang

    2016-08-01

    The tumor microenvironment impacts tumor progression and individual cells, including CD4(+) T cells, which have been detected in bladder cancer tissues. The detailed mechanism of how these T cells were recruited to the bladder cancer tumor and their impact on bladder cancer progression, however, remains unclear. Using a human clinical bladder cancer sample survey and in vitro coculture system, we found that bladder cancer has a greater capacity to recruit T cells than surrounding normal bladder tissues. The consequences of higher levels of recruited T cells in bladder cancer included increased bladder cancer metastasis. Mechanism dissection revealed that infiltrating T cells might function through secreting the cytokine IL1, which increases the recruitment of T cells to bladder cancer and enhances the bladder cancer androgen receptor (AR) signaling that results in increased bladder cancer cell invasion via upregulation of hypoxia-inducible factor-1α (HIF1α)/VEGFa expression. Interruption of the IL1→AR→HIF1α→VEGFa signals with inhibitors of HIF1α or VEGFa partially reversed the enhanced bladder cancer cell invasion. Finally, in vivo mouse models of xenografted bladder cancer T24 cells with CD4(+) T cells confirmed in vitro coculture studies and concluded that infiltrating CD4(+) T cells can promote bladder cancer metastasis via modulation of the IL1→AR→HIF1α→VEGFa signaling. Future clinical trials using small molecules to target this newly identified signaling pathway may facilitate the development of new therapeutic approaches to better suppress bladder cancer metastasis. Mol Cancer Ther; 15(8); 1943-51. ©2016 AACR. ©2016 American Association for Cancer Research.

  6. Construction and evaluation of urinary bladder bioreactor for urologic tissue-engineering purposes.

    LENUS (Irish Health Repository)

    Davis, Niall F

    2012-01-31

    OBJECTIVE: To design and construct a urinary bladder bioreactor for urologic tissue-engineering purposes and to compare the viability and proliferative activity of cell-seeded extracellular matrix scaffolds cultured in the bioreactor with conventional static growth conditions. MATERIALS AND METHODS: A urinary bladder bioreactor was designed and constructed to replicate physiologic bladder dynamics. The bioreactor mimicked the filling pressures of the human bladder by way of a cyclical low-delivery pressure regulator. In addition, cell growth was evaluated by culturing human urothelial cells (UCs) on porcine extracellular matrix scaffolds in the bioreactor and in static growth conditions for 5 consecutive days. The attachment, viability, and proliferative potential were assessed and compared with quantitative viability indicators and by fluorescent markers for intracellular esterase activity and plasma membrane integrity. Scaffold integrity was characterized with scanning electron microscopy and 4\\

  7. Effects of Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] on the urinary bladder of male Wistar rats

    International Nuclear Information System (INIS)

    Nascimento, Merielen Garcia; Cotrim Sartor de Oliveira, Maria Luiza; Lima, Adriano Silva; Camargo, Joao Lauro Viana de

    2006-01-01

    Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide widely used on agricultural crops such as soy, cotton and sugar cane. In a previous long-term study this herbicide exerted carcinogenic activity on the urinary bladder mucosa of male Wistar rats. In general, the genotoxic and mutagenic potentials of Diuron are considered to be negative. The present study aimed to evaluate the mode of action of Diuron on the urinary bladder mucosa of male Wistar rats. Six-week old male Wistar rats were fed pelleted Nuvilab diet mixed with Diuron at 125, 500 and 2500 ppm. As a positive control, 8.3% sodium saccharin (NaS) was fed in the diet. Preceding the sacrifice of the animals at the 20th week, urinary pH was measured and the genotoxic potential of Diuron was evaluated by the comet assay. Histological urothelial lesions in the urinary bladder and in the renal pelvis mucosa, cell proliferation/apoptosis evaluations, and scanning electron microscopy (SEM) of the urinary bladder mucosa were also performed. No DNA changes were found in urothelial or peripheral blood cells, and urinary pH was comparable to controls in all Diuron groups. In the urinary bladder urothelium, the incidence of simple hyperplasia (SH) by light microscopy was significantly increased (7/10; p < 0.005) in the 2500 ppm Diuron group but not at the lower doses. By SEM, three of five animals treated with 2500 ppm Diuron showed urothelial cell necrosis and hyperplasia. In the renal pelvis, the incidence of SH was significantly increased in the Diuron 500 and 2500 ppm and in the NaS 8.3% groups. Cell proliferation was significantly increased in the Diuron 2500 ppm (p < 0.05) and NaS 8.3% (p < 0.05) groups. The results indicate that a high dietary concentration of Diuron is associated with urothelial necrosis and continuous regenerative cell proliferation that leads to urothelial hyperplasia

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

    Directory of Open Access Journals (Sweden)

    Hsieh Fu-Chuan

    2008-10-01

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

  9. 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

    2011-03-01

    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.

  10. Assessment of inhibitory effects on major human cytochrome P450 enzymes by spasmolytics used in the treatment of overactive bladder syndrome.

    Science.gov (United States)

    Dahlinger, Dominik; Aslan, Sevinc; Pietsch, Markus; Frechen, Sebastian; Fuhr, Uwe

    2017-07-01

    The objective of this study was to examine the inhibitory potential of darifenacin, fesoterodine, oxybutynin, propiverine, solifenacin, tolterodine and trospium chloride on the seven major human cytochrome P450 enzymes (CYP) by using a standardized and validated seven-in-one cytochrome P450 cocktail inhibition assay. An in vitro cocktail of seven highly selective probe substrates was incubated with human liver microsomes and varying concentrations of the seven test compounds. The major metabolites of the probe substrates were simultaneously analysed using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Enzyme kinetics were estimated by determining IC 50 and K i values via nonlinear regression. Obtained K i values were used for predictions of potential clinical impact of the inhibition using a static mechanistic prediction model. In this study, 49 IC 50 experiments were conducted. In six cases, IC 50 values lower than the calculated threshold for drug-drug interactions (DDIs) in the gut wall were observed. In these cases, no increase in inhibition was determined after a 30 min preincubation. Considering a typical dosing regimen and applying the obtained K i values of 0.72 µM (darifenacin, 15 mg daily) and 7.2 µM [propiverine, 30 mg daily, immediate release (IR)] for the inhibition of CYP2D6 yielded a predicted 1.9-fold and 1.4-fold increase in the area under the curve (AUC) of debrisoquine (CYP2D6 substrate), respectively. Due to the inhibition of the particular intestinal CYP3A4, the obtained K i values of 14 µM of propiverine (30 mg daily, IR) resulted in a predicted doubling of the AUC for midazolam (CYP3A4 substrate). In vitro / in vivo extrapolation based on pharmacokinetic data and the conducted screening experiments yielded similar effects of darifenacin on CYP2D6 and propiverine on CYP3A4 as obtained in separately conducted in vivo DDI studies. As a novel finding, propiverine was identified to potentially inhibit CYP2D6 at

  11. Bladder symptoms assessed with overactive bladder questionnaire in Parkinson's disease.

    Science.gov (United States)

    Iacovelli, Elisa; Gilio, Francesca; Meco, Giuseppe; Fattapposta, Francesco; Vanacore, Nicola; Brusa, Livia; Giacomelli, Elena; Gabriele, Maria; Rubino, Alfonso; Locuratolo, Nicoletta; Iani, Cesare; Pichiorri, Floriana; Colosimo, Carlo; Carbone, Antonio; Palleschi, Giovanni; Inghilleri, Maurizio

    2010-07-15

    In Parkinson's disease (PD) the urinary dysfunction manifests primarily with symptoms of overactive bladder (OAB). The OAB questionnaire (OAB-q) is a measure designed to assess the impact of OAB symptoms on health-related quality of life. In this study, we quantified the urinary symptoms in a large cohort of PD patients by using the OAB-q short form. Possible correlations between the OAB-q and clinical features were tested. Three hundred and two PD patients were enrolled in the study. Correlations between the OAB-q and sex, age, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), Hoehn-Yahr (H-Y) staging, disease duration, and treatment were analyzed. Data were compared with a large cohort of 303 age-matched healthy subjects. The OAB-q yielded significantly higher scores in PD patients than in healthy subjects. In the group of PD patients, all the variables tested were similar between men and women. Pearson's coefficient showed a significant correlation between mean age, disease duration, mean OAB-q scores, UPDRS-III scores, and H-Y staging. A multiple linear regression analysis showed that OAB-q values were significantly influenced by age and UPDRS-III. No statistical correlations were found between OAB-q scores and drug therapy or the equivalent levodopa dose, whilst the items relating to the nocturia symptoms were significantly associated with the equivalent levodopa dose. Our findings suggest that bladder dysfunction assessed by OAB-q mainly correlates with UPDRS-III scores for severity of motor impairment, possibly reflecting the known role of the decline in nigrostriatal dopaminergic function in bladder dysfunction associated with PD and patients' age. Our study also suggests that the OAB-q is a simple, easily administered test that can objectively evaluate bladder function in patients with PD.

  12. Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM.

    Science.gov (United States)

    Bryan, R T; Regan, H L; Pirrie, S J; Devall, A J; Cheng, K K; Zeegers, M P; James, N D; Knowles, M A; Ward, D G

    2015-03-17

    Better biomarkers must be found to develop clinically useful urine tests for bladder cancer. Proteomics can be used to identify the proteins released by cancer cell lines and generate candidate markers for developing such tests. We used shotgun proteomics to identify proteins released into culture media by eight bladder cancer cell lines. These data were compared with protein expression data from the Human Protein Atlas. Epidermal growth factor receptor (EGFR) was identified as a candidate biomarker and measured by ELISA in urine from 60 noncancer control subjects and from 436 patients with bladder cancer and long-term clinical follow-up. Bladder cancer cell lines shed soluble EGFR ectodomain. Soluble EGFR is also detectable in urine and is highly elevated in some patients with high-grade bladder cancer. Urinary EGFR is an independent indicator of poor bladder cancer-specific survival with a hazard ratio of 2.89 (95% CI 1.81-4.62, Pbladder cancer-specific survival and have prognostic value over and above that provided by standard clinical observations. Measuring urinary EGFR and EpCAM may represent a simple and useful approach for fast-tracking the investigation and treatment of patients with the most aggressive bladder cancers.

  13. Are you experienced? Understanding bladder innate immunity in the context of recurrent urinary tract infection

    Science.gov (United States)

    O’Brien, Valerie P.; Hannan, Thomas J.; Schaeffer, Anthony J.; Hultgren, Scott J.

    2015-01-01

    Purpose of review Recurrent urinary tract infection (rUTI) is a serious clinical problem, yet effective therapeutic options are limited, especially against multidrug-resistant uropathogens. In this review, we explore the development of a clinically relevant model of rUTI in previously infected mice and review recent developments in bladder innate immunity that may affect susceptibility to rUTI. Recent findings Chronic bladder inflammation during prolonged bacterial cystitis in mice causes bladder mucosal remodelling that sensitizes the host to rUTI. Although constitutive defenses help prevent bacterial colonization of the urinary bladder, once infection occurs, induced cytokine and myeloid cell responses predominate and the balance of immune cell defense and bladder immunopathology is critical for determining disease outcome, in both naïve and experienced mice. In particular, the maintenance of the epithelial barrier appears to be essential for preventing severe infection. Summary The innate immune response plays a key role in determining susceptibility to rUTI. Future studies should be directed towards understanding how the innate immune response changes as a result of bladder mucosal remodelling in previously infected mice, and validating these findings in human clinical specimens. New therapeutics targeting the immune response should selectively target the induced innate responses that cause bladder immunopathology, while leaving protective defenses intact. PMID:25517222

  14. Urothelial (transitional cell) papilloma of the urinary bladder: a clinicopathologic study of 26 cases.

    Science.gov (United States)

    McKenney, Jesse K; Amin, Mahul B; Young, Robert H

    2003-07-01

    The existence of a papillary lesion of the urinary bladder with a benign clinical course and recognizable morphologic features that merit the benign categorization "papilloma" has been controversial. The clinical aspects and histologic features of these lesions remain to be fully elucidated. We have studied the clinicopathologic features of 26 patients with urothelial papillomas and correlated them with outcome. Papillomas occurred in two distinct clinical settings: (1) de novo neoplasms (23/26) or (2) those occurring in patients with a known clinical history of bladder cancer ("secondary" papillomas; 3/26). Follow-up information was available in 14/23 of the de novo cases (mean = 39 mo) and in 3/3 secondary cases (mean = 24 mo). Patients with de novo papillomas had a mean age of 46 years; 16 were male and 7 were female. Twelve of 14 had a benign clinical course with no recurrences; 1 developed a recurrent papilloma at 3 years, and 1 developed a pT3a high-grade papillary urothelial carcinoma at 4 years. Patients with secondary papillomas had a mean age of 66 years; two were male and one was a female. One of these patients developed two additional recurrences, and two patients had no new recurrences. Morphologically, the papillary architecture ranged from a common simple, nonhierarchical arrangement to, infrequently, more complex anastomosing papillae with budding. The individual papillae ranged from small (most common), with scant stroma and slender fibrovascular cores, to large, with marked stromal edema and/or cystitis cystica-like urothelial invaginations. Common to all was a lining of normal-appearing urothelium without hyperplasia, maintenance of normal polarity, and frequent prominence of the umbrella cell layer. Overall, no patient with a diagnosis of papilloma died of disease; only one patient with a de novo lesion (7.0%) had a recurrent papilloma, and 1/14 (7.0%) progressed to a higher grade and stage of disease, although this patient was on

  15. Chloroquine and hydroxychloroquine inhibit bladder cancer cell growth by targeting basal autophagy and enhancing apoptosis

    Directory of Open Access Journals (Sweden)

    Yi-Chia Lin

    2017-05-01

    Full Text Available Chloroquine (CQ and hydroxychloroquine (HCQ, two antimalarial drugs, are suggested to have potential anticancer properties. in the present study, we investigated the effects of CQ and HCQ on cell growth of bladder cancer with emphasis on autophagy inhibition and apoptosis induction in vitro. The results showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell lines (including RT4, 5637, and T24 in a time- and dose-dependent fashion, especially in advanced bladder cancer cell lines (5637 and T24 compared to immortalized uroepithelial cells (SV-Huc-1 or other reference cancer cell lines (PC3 and MCF-7. We found that 24-hour treatment of CQ or HCQ significantly decreased the clonogenic formation in 5637 and T24 cells compared to SV-Huc-1. As human bladder cancer tumor exhibits high basal level of autophagic activities, we detected the autophagic flux in cells treated with CQ and HCQ, showing an alternation in LC3 flux in CQ- or HCQ-treated cells. Moreover, bladder cancer cells treated with CQ and HCQ underwent apoptosis, resulting in increased caspase 3/7 activities, increased level of cleaved poly(ADP-ribose polymerase (PARP, caspase 3, and DNA fragmentation. Given these results, targeting autophagy with CQ and HCQ represents an effective cancer therapeutic strategy against human bladder cancer.

  16. Chloroquine and hydroxychloroquine inhibit bladder cancer cell growth by targeting basal autophagy and enhancing apoptosis.

    Science.gov (United States)

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

    2017-05-01

    Chloroquine (CQ) and hydroxychloroquine (HCQ), two antimalarial drugs, are suggested to have potential anticancer properties. in the present study, we investigated the effects of CQ and HCQ on cell growth of bladder cancer with emphasis on autophagy inhibition and apoptosis induction in vitro. The results showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell lines (including RT4, 5637, and T24) in a time- and dose-dependent fashion, especially in advanced bladder cancer cell lines (5637 and T24) compared to immortalized uroepithelial cells (SV-Huc-1) or other reference cancer cell lines (PC3 and MCF-7). We found that 24-hour treatment of CQ or HCQ significantly decreased the clonogenic formation in 5637 and T24 cells compared to SV-Huc-1. As human bladder cancer tumor exhibits high basal level of autophagic activities, we detected the autophagic flux in cells treated with CQ and HCQ, showing an alternation in LC3 flux in CQ- or HCQ-treated cells. Moreover, bladder cancer cells treated with CQ and HCQ underwent apoptosis, resulting in increased caspase 3/7 activities, increased level of cleaved poly(ADP-ribose) polymerase (PARP), caspase 3, and DNA fragmentation. Given these results, targeting autophagy with CQ and HCQ represents an effective cancer therapeutic strategy against human bladder cancer. Copyright © 2017. Published by Elsevier Taiwan.

  17. MRI of perforated gall bladder

    International Nuclear Information System (INIS)

    Sood, B.; Jain, M.; Khandelwal, N.; Singh, P.; Suri, S.

    2002-01-01

    Gall bladder perforation is a dreaded complication of acute cholecystitis that, if not diagnosed early in the course, might have a poor prognosis. Both CT and ultrasonography have been used until now extensively for the diagnosis of acute cholecystitis, but diagnosis of perforation is always difficult. Magnetic resonance, by its superior soft tissue resolution and multiplanar capability, is a better modality and should fare better than ultrasonography and CT, as demonstrated in our case. Magnetic resonance imaging demonstrates the wall of the gall bladder and defects to a much better advantage and more convincingly. In addition, MR colangiopancreatography images demonstrate the biliary tree better than other modalities. We suggest that in the case of acute cholecystitis, if perforation is suspected and CT and ultrasonography are not conclusive, MR should be the modality of choice. It can be used as a first line of investigation; however, it might not be cost-effective. Copyright (2002) Blackwell Science Pty Ltd

  18. Orthotopic neo- bladder in women.

    Science.gov (United States)

    Schettini, Manlio

    2010-12-01

    Radical cystectomy is the most effective treatment madality for high grade urinary bladder carcinoma and orthotopic reconstruction is the better urinary diversion modality also in women. From 2002 to 2007 we performed 14 radical cystectomies followed by orthotopic reconstruction in women aged between 47 and 68 years (mean age 56) affected by urinary bladder carcinoma. Our reconstructive technique requires the preparation of two strips of the recti muscles fascia, the sectioning of the bladder neck and, when the uterus is present, hysteroannessiectomy and cystectomy en block leaving intact the lateral and inferior vaginal walls. The pelvic floor is stabilized by a colposacropexis with a prosthesis and placing an omental flap over the prosthesis. The orthotopic reconstruction is achieved via a neobladder according to the Padovana technique. The ureters are anastomized to the neobladder and splinted with single J stents. The pathological examination demonstrated in all patients the presence of a high grade carcinoma (G3): more specifically 4 patients had a full thickness intramural infiltration (T2), 2 patients had involvment of the perivescical fat (T3) ad 8 patients were in T1 stage. Lymphnodes were negative for tumour (NO). In 8 patients blood transfusions were necessary to treat post surgical anemia. No significant intra-, peri- or post operative complications were noted. The mean follow-up was 45 months: a patient died for diffuse metastatic disease after 11 months. The remaining patients are still alive and report normal lifestyle: 10 with normal micturition and 4 with urinary retention treated with intermittent self-catetherization. Two patients report nocturnal incontinence treated with hourly micturition and one pad. The five patients who had normal preoperative sexual intercourse resumed a normal sexual activity. The possibility to orthotopically recontruct the female urinary bladder has been established long time after the introduction of orthotopic

  19. Epitheloid hemangioendothelioma of urinary bladder

    Directory of Open Access Journals (Sweden)

    Narmada P Gupta

    2008-01-01

    Full Text Available Epitheloid hemangioendothelioma is an uncommon vascular neoplasm and has an unpredictable clinical behavior. It is characterized by round or spindle-shaped endothelial cells with cytoplasmic vacuolation. Most often, epitheloid hemangioendothelioma arise from the soft tissues of the upper and lower extremities and it has borderline malignant potential. We describe the first reported case of epitheloid hemangioendothelioma in the urinary bladder, which was treated by transurethral resection. The diagnosis was confirmed by immunohistochemistry.

  20. Bladder rupture caused by postpartum urinary retention.

    Science.gov (United States)

    Dueñas-García, Omar Felipe; Rico, Hugo; Gorbea-Sanchez, Viridiana; Herrerias-Canedo, Tomas

    2008-08-01

    Postpartum bladder rupture is an uncommon surgical emergency and a diagnostic challenge. A primigravida delivered a healthy newborn without complications at 39.4 weeks of gestation. The patient was admitted 80 hours postpartum with abdominal pain, oliguria, hematuria, and pain that worsened during the previous 4 hours. An inserted Foley catheter drained only a small amount of urine, and serum creatinine was elevated (3.5 mg/dL). A laparotomy was performed and revealed a 10-cm hole in the urinary bladder. The bladder was repaired and the patient was discharged 15 days after surgery. The follow-up cystoscopy revealed adequate healing of the bladder. Urinary retention can lead to serious complications, including bladder rupture. Postpartum bladder rupture due to urinary retention should be ruled out if there is a history of abdominal pain, oliguria, and elevated of serum creatinine.

  1. Bladder injuries frequently missed in polytrauma patients

    Directory of Open Access Journals (Sweden)

    Tanweer Karim

    2010-05-01

    Full Text Available Tanweer Karim, Margaret Topno, Vinod Sharma, Raymond Picardo, Ankur HastirSurgery, MGM Medical College, Kamothe, Navi Mumbai, IndiaAbstract: Bladder injuries are very common in patients who have had road traffic accidents. The method of diagnosis and management of such injuries is well established and accepted. However, trauma to the bladder can be associated with other life-threatening injuries which are frequently missed, and often diagnosed during laparotomy for other reasons. The aim of this study was to diagnose bladder injury in polytrauma patients as early as possible, taking into consideration the fact that these patients are hemodynamically unstable and require rapid evaluation and management. In order to achieve our objective, we used bedside sonography with retrograde instillation of normal saline to diagnose bladder injury in addition to use of the conventional retrograde cystogram.Keywords: bladder injury, bladder rupture, retrograde cystogram

  2. Transurethral resection for botryoid bladder rhabdomyosarcoma

    Directory of Open Access Journals (Sweden)

    Mitsuyuki Nakata

    2018-01-01

    Full Text Available The outcome of multimodal therapy for localized bladder rhabdomyosarcoma is quite good in terms of morbidity, and conservative surgery is generally recommended. However, in cases originating in the bladder neck, tumorectomy or partial cystectomy has adverse effects on bladder function. A 2-year-old girl underwent transurethral resection of a bladder tumor (TUR-BT, chemotherapy consisting of vincristine, actinomycin-D, and cyclophosphamide, and radiotherapy. She was in remission for 3 years when frequent urination became evident. Her bladder capacity and compliance were low; however, her urinary symptom was controlled using anticholinergic medication. Accordingly, TUR-BT could be an optional approach for bladder rhabdomyosarcoma. Keywords: Rhabdomyosarcoma, Transurethral resection, Conservative surgery

  3. Duplex gall bladder: bystander or culprit.

    Science.gov (United States)

    Kumar, Jogender; Yadav, Arushi

    2017-08-30

    Gall bladder (GB) duplication is a rare anatomical malformation, which can be detected by preoperative imaging study. We present a case of duplex gall bladder in a 14-year-old boy who presented with abdominal pain. On ultrasound, he had right nephrolithiasis and duplex gall bladder. Duplex gall bladder was confirmed on MR cholangiopancreatography. There was a dilemma for surgical management of duplex gall bladder; however, he became asymptomatic after conservative treatment. Prophylactic surgery is not recommended for asymptomatic incidentally detected duplex gall bladder. Radiologists and paediatric surgeons should be sensitised about the exact anatomy of this entity. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Calcium transport in turtle bladder

    International Nuclear Information System (INIS)

    Sabatini, S.; Kurtzman, N.A.

    1987-01-01

    Unidirectional 45 Ca fluxes were measured in the turtle bladder under open-circuit and short-circuit conditions. In the open-circuited state net calcium flux (J net Ca ) was secretory (serosa to mucosa). Ouabain reversed J net Ca to an absorptive flux. Amiloride reduced both fluxes such that J net Ca was not significantly different from zero. Removal of mucosal sodium caused net calcium absorption; removal of serosal sodium caused calcium secretion. When bladders were short circuited, J net Ca decreased to approximately one-third of control value but remained secretory. When ouabain was added under short-circuit conditions, J net Ca was similar in magnitude and direction to ouabain under open-circuited conditions (i.e., absorptive). Tissue 45 Ca content was ≅30-fold lower when the isotope was placed in the mucosal bath, suggesting that the apical membrane is the resistance barrier to calcium transport. The results obtained in this study are best explained by postulating a Ca 2+ -ATPase on the serosa of the turtle bladder epithelium and a sodium-calcium antiporter on the mucosa. In this model, the energy for calcium movement would be supplied, in large part, by the Na + -K + -ATPase. By increasing cell sodium, ouabain would decrease the activity of the mucosal sodium-calcium exchanger (or reverse it), uncovering active calcium transport across the serosa

  5. Bladder tissue engineering through nanotechnology.

    Science.gov (United States)

    Harrington, Daniel A; Sharma, Arun K; Erickson, Bradley A; Cheng, Earl Y

    2008-08-01

    The field of tissue engineering has developed in phases: initially researchers searched for "inert" biomaterials to act solely as replacement structures in the body. Then, they explored biodegradable scaffolds--both naturally derived and synthetic--for the temporary support of growing tissues. Now, a third phase of tissue engineering has developed, through the subcategory of "regenerative medicine." This renewed focus toward control over tissue morphology and cell phenotype requires proportional advances in scaffold design. Discoveries in nanotechnology have driven both our understanding of cell-substrate interactions, and our ability to influence them. By operating at the size regime of proteins themselves, nanotechnology gives us the opportunity to directly speak the language of cells, through reliable, repeatable creation of nanoscale features. Understanding the synthesis of nanoscale materials, via "top-down" and "bottom-up" strategies, allows researchers to assess the capabilities and limits inherent in both techniques. Urology research as a whole, and bladder regeneration in particular, are well-positioned to benefit from such advances, since our present technology has yet to reach the end goal of functional bladder restoration. In this article, we discuss the current applications of nanoscale materials to bladder tissue engineering, and encourage researchers to explore these interdisciplinary technologies now, or risk playing catch-up in the future.

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

    International Nuclear Information System (INIS)

    Onozawa, Mizuki; Miyanaga, Naoto; Hinotsu, Shiro

    2012-01-01

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

  7. Mandatory role of proteinase-activated receptor 1 in experimental bladder inflammation

    Directory of Open Access Journals (Sweden)

    Davis Carole A

    2007-03-01

    Full Text Available Abstract Background In general, inflammation plays a role in most bladder pathologies and represents a defense reaction to injury that often times is two edged. In particular, bladder neurogenic inflammation involves the participation of mast cells and sensory nerves. Increased mast cell numbers and tryptase release represent one of the prevalent etiologic theories for interstitial cystitis and other urinary bladder inflammatory conditions. The activity of mast cell-derived tryptase as well as thrombin is significantly increased during inflammation. Those enzymes activate specific G-protein coupled proteinase-activated receptors (PARs. Four PARs have been cloned so far, and not only are all four receptors highly expressed in different cell types of the mouse urinary bladder, but their expression is altered during experimental bladder inflammation. We hypothesize that PARs may link mast cell-derived proteases to bladder inflammation and, therefore, play a fundamental role in the pathogenesis of cystitis. Results Here, we demonstrate that in addition to the mouse urinary bladder, all four PA receptors are also expressed in the J82 human urothelial cell line. Intravesical administration of PAR-activating peptides in mice leads to an inflammatory reaction characterized by edema and granulocyte infiltration. Moreover, the inflammatory response to intravesical instillation of known pro-inflammatory stimuli such as E. coli lipopolysaccharide (LPS, substance P, and antigen was strongly attenuated by PAR1-, and to a lesser extent, by PAR2-deficiency. Conclusion Our results reveal an overriding participation of PAR1 in bladder inflammation, provide a working model for the involvement of downstream signaling, and evoke testable hypotheses regarding the role of PARs in bladder inflammation. It remains to be determined whether or not mechanisms targeting PAR1 gene silencing or PAR1 blockade will ameliorate the clinical manifestations of cystitis.

  8. Giant Leiomyosarcoma of the Urinary Bladder.

    Science.gov (United States)

    Ribeiro, José G A; Klojda, Carlos A B; Araújo, Claudio P De; Pires, Lucas A S; Babinski, Marcio A

    2016-05-01

    The bladder leiomyosarcoma is a rare and agressive mesenchymal tumour, and adult women of reproductive age have a higher incidence of developing the bladder leiomyosarcoma. The pathophysiology of the disease is not certain, and its main symptoms are hematuria, dysuria and abdominal pain. There are not a considerable amount of cases described in the literature. We report a case of a giant leiomyosarcoma of the urinary bladder in a 31-year-old woman.

  9. Bladder wash cytology, quantitative cytology, and the qualitative BTA test in patients with superficial bladder cancer

    NARCIS (Netherlands)

    van der Poel, H. G.; van Balken, M. R.; Schamhart, D. H.; Peelen, P.; de Reijke, T.; Debruyne, F. M.; Schalken, J. A.; Witjes, J. A.

    1998-01-01

    Two new methods for the detection of transitional tumor cells in bladder wash (karyometry: QUANTICYT) and voided urine material (BARD BTA test) were compared with bladder wash cytology for the prediction of histology and tumor recurrence. Bladder wash material and voided urine were sampled from 138

  10. Effects of acute urinary bladder overdistension on bladder response during sacral neurostimulation.

    Science.gov (United States)

    Bross, S; Schumacher, S; Scheepe, J R; Zendler, S; Braun, P M; Alken, P; Jünemann, K

    1999-10-01

    Urinary retention and micturition disorders after overdistension are clinically well-known complications of subvesical obstruction. We attempted to evaluate whether bladder overdistension influences bladder response and whether overdistension supports detrusor decompensation. Following lumbal laminectomy in 9 male foxhounds, the sacral anterior roots S2 and S3 were placed into a modified Brindley electrode for reproducible and controlled detrusor activation. The bladder was filled in stages of 50 ml from 0 to 700 ml, corresponding to an overdistension. At each volume, the bladder response during sacral anterior root stimulation was registered. After overdistension, the bladder was refilled stepwise from 0 to 300 ml and stimulated. In all dogs, the bladder response was influenced by the intravesical volume. The maximum pressure (mean 69.1 cm H(2)O) was observed at mean volume of 100 ml. During overdistension, a significant reduction in bladder response of more than 80% was seen. After overdistension, a significant reduction in intravesical pressure of 19.0% was observed. In 2 cases, reduction in bladder response was more than 50% after a single overdistension. We conclude that motoric bladder function is influenced during and after overdistension. A single bladder overdistension can support acute and long-lasting detrusor decompensation. In order to protect motoric bladder function, bladder overdistension must be prevented.

  11. Full-thickness endometriosis of the bladder

    DEFF Research Database (Denmark)

    Kjer, Jens Jørgen; Kristensen, Jens; Hartwell, Dorthe

    2014-01-01

    referral centres in Denmark for surgical treatment of stage III and IV endometriosis. POPULATION: Thirty-one women with deep infiltrating bladder endometriosis. METHODS: All women presenting in the Department of Obstetrics and Gynaecology with deep infiltrating bladder endometriosis between March 2002...... and March 2011. We included only patients with symptomatic full-thickness bladder detrusor endometriosis and mucosal involvement. All patients had had bladder symptoms for two to seven years. MAIN OUTCOME MEASURES: Symptoms after surgery and recurrence rate. RESULTS: The main preoperative symptom...

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

    Science.gov (United States)

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

    2015-01-01

    Urinary bladder cancer is a worldwide concern because of its level of incidence and recurrence. To search an effective therapeutic strategy for urinary bladder cancer, it is important to identify proteins involved in tumorigenesis that could serve as potential targets for diagnosis and treatment. G-protein-coupled receptors (GPRs) constitute a large protein family of receptors that sense molecules outside the cell and activate signal transduction pathways and cellular responses inside the cell. GPR137 is a newly discovered human gene encoding orphan GPRs. In this study, we aimed to investigate the physiological role of GPR137 in urinary bladder cancer. The effect of GPR137 on cell growth was examined via an RNA interference (RNAi) lentivirus system in two human urinary bladder cancer cell lines BT5637 and T24. Lentivirus-mediated RNAi could specifically suppressed GPR137 expression in vitro, resulting in alleviated cell viability and impaired colony formation, as well as blocks G0/G1 and S phases of the cell cycle. These results suggested GPR137 as an essential player in urinary bladder cancer cell growth, and it may serve as a potential target for gene therapy in the treatment of urinary bladder cancer. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

  13. Computational model of the human urinary bladder

    OpenAIRE

    Silva Araujo Monteiro, Virginia

    2013-01-01

    La propuesta de una vejiga artificial es un obstáculo a trasponer. El cáncer de vejiga está entre los casos más frecuentes de enfermedades oncológicas en Estados Unidos y Europa. Ese cáncer es considerado un problema médico importante una vez que esa enfermedad presenta altas tasas de re-ocurrencia, muchas veces llevando a la remoción del órgano. La solución más sofisticada para remplazar ese órgano es la vejiga ileal, que consiste en una neovejiga hecha de tejido intestinal del enfermo. Desa...

  14. Expression of OCT4A: The First Step to the Next Stage of Urothelial Bladder Cancer Progression

    Directory of Open Access Journals (Sweden)

    Wojciech Jóźwicki

    2014-09-01

    Full Text Available OCT4 (octamer-binding transcription factor is a transcription factor responsible for maintaining the pluripotent properties of embryonic stem cells. In this paper, we present the results of studies to investigate the role of the OCT4 splicing variant in urothelial bladder cancer and the relationship between the OCT4 phenotype and the morphological parameters of tumor malignancy. Ninety patients who received a cystectomy for bladder cancer were enrolled. The expression of OCT4 protein was analyzed by immunohistochemistry. The ratio of OCT4-positive cells was the lowest in pT1 (pathological assessment (p—tumor extent confined to mucosa (T1 tumors and the highest in pTis (non-papillary tumor extent confined to urothelium and pT2 (tumor extent including muscularis propria tumors. Information about the percentage of OCT4A-positive tumor cells could facilitate choosing the treatment mode in borderline pTis–pT1 (crossing the border of the basement membrane; the first stage of progression and pT1–pT2 (crossing the border of the muscularis propria; the second stage of progression cases: a higher percentage of OCT4A-positive cells should support more radical therapy. A significantly higher percentage of cases with moderate OCT4 intensity was found in metastasizing (the third stage of progression cases with >2 positive lymph nodes. The percentage of OCT4-positive cells was significantly higher for cancers with a high grade, higher non-classic differentiation number and greater aggressiveness of invasion. The differentiation, maturation and aggressiveness of tumor invasion appear to depend on the expression of the OCT4 phenotype in cancer cells, similar to the successive stages of malignancy progression in urothelial cancer.

  15. Expression status and prognostic significance of mammalian target of rapamycin pathway members in urothelial carcinoma of urinary bladder after cystectomy.

    Science.gov (United States)

    Schultz, Luciana; Albadine, Roula; Hicks, Jessica; Jadallah, Sana; DeMarzo, Angelo M; Chen, Ying-Bei; Nielsen, Matthew E; Neilsen, Matthew E; Gonzalgo, Mark L; Sidransky, David; Schoenberg, Mark; Netto, George J

    2010-12-01

    Bladder urothelial carcinoma has high rates of mortality and morbidity. Identifying novel molecular prognostic factors and targets of therapy is crucial. Mammalian target of rapamycin (mTOR) pathway plays a pivotal role in establishing cell shape, migration, and proliferation. Tissue microarrays were constructed from 132 cystectomies (1994-2002). Immunohistochemistry was performed for Pten, c-myc, p27, phosphorylated (phos)Akt, phosS6, and 4E-BP1. Markers were evaluated for pattern, percentage, and intensity of staining. Mean length of follow-up was 62.6 months (range, 1-182 months). Disease progression, overall survival (OS), and disease-specific survival (DSS) rates were 42%, 60%, and 68%, respectively. Pten showed loss of expression in 35% of bladder urothelial carcinoma. All markers showed lower expression in invasive bladder urothelial carcinoma compared with benign urothelium with the exception of 4E-BP1. Pten, p27, phosAkt, phosS6, and 4E-BP1 expression correlated with pathologic stage (pathological stage; P<.03). Pten, 4E-BP1, and phosAkt expression correlated with divergent aggressive histology and invasion. phosS6 expression inversely predicted OS (P=.01), DSS (P=.001), and progression (P=.05). c-myc expression inversely predicted progression (P=.01). In a multivariate analysis model that included TNM stage grouping, divergent aggressive histology, concomitant carcinoma in situ, phosS6, and c-myc expression, phosS6 was an independent predictor of DSS (P=.03; hazard ratio [HR], -0.19), whereas c-myc was an independent predictor of progression (P=.02; HR, -0.38). In a second model substituting organ-confined disease and lymph node status for TNM stage grouping, phosS6 and c-myc remained independent predictors of DSS (P=.03; HR, -0.21) and progression (P=.03; HR, -0.34), respectively. We found an overall down-regulation of mTOR pathway in bladder urothelial carcinoma. phosS6 independently predicted DSS, and c-myc independently predicted progression

  16. Bladder extension variability during pelvic external beam radiotherapy with a full or empty bladder

    International Nuclear Information System (INIS)

    Pinkawa, Michael; Asadpour, Branka; Siluschek, Jaroslav; Gagel, Bernd; Piroth, Marc D.; Demirel, Cengiz; Eble, Michael J.

    2007-01-01

    Background and purpose: Varying bladder fillings during radiotherapy lead to a changing dose-volume load to the bladder and adjacent structures. The aim of the study was to compare the extent of bladder wall movements during parallel series with full bladder (FB) and empty bladder (EB). Materials and methods: Three hundred and forty serial computed tomography (CT) scans were performed in 50 patients scheduled for primary and postoperative radiotherapy for prostate cancer. Each patient underwent two CT scans (with FB and EB) before and 2-3 times during radiotherapy. Displacements of the bladder wall were compared and correlated with changing bladder fillings. Results: The variability of FB was larger compared to EB volume (standard deviation of 124cc and 56cc; p < 0.01), but significant bladder wall displacement variabilities were only found at the anterior and superior borders. Within a bladder volume range between -100 and +200 ml relative to the FB planning scan, the mean bladder wall displacement remained <5 mm at the inferior, lateral, and posterior borders - as opposed to 15 and 21 mm at the anterior and superior borders. Conclusions: Treating the pelvis with EB compared to FB, bladder wall displacement can be only reduced at the superior and anterior borders. FB wall displacements are comparable with EB displacements at all other borders

  17. Evaluation of associations between lifetime exposure to drinking water disinfection by-products and bladder cancer in dogs.

    Science.gov (United States)

    Backer, Lorraine C; Coss, Angela M; Wolkin, Amy F; Flanders, W Dana; Reif, John S

    2008-06-01

    To assess the risk of bladder cancer in dogs from exposure to drinking water disinfection by-products and determine whether dogs could serve as sentinels for human bladder cancer associated with such exposures. Case-control study. 100 dogs with cancer of the urinary bladder and 100 control dogs. Case and control dogs were frequency-matched by age (within 2 years) and sex. Owners of dogs enrolled provided verbal informed consent and were interviewed by telephone. The telephone questionnaire included a complete residence history for each dog. Each dog's total exposure history to trihalomethanes was reconstructed from its residence history and corresponding drinking water utility company data. No association was detected between increasing years of exposure to chlorinated drinking water and risk of bladder cancer. Dogs with bladder cancer were exposed to higher total trihalomethanes concentrations than control dogs; however, the difference was not significant. Although humans and their dogs live in the same household, the activity patterns of dogs may lead to lower exposures to household tap water. Thus, although exposure to disinfection by-products in tap water may be a risk factor for human bladder cancer, this may not be true for canine bladder cancer at the concentrations at which dogs are exposed.

  18. Transurethral laser therapy of tumours of the bladder

    International Nuclear Information System (INIS)

    Noeske, H.D.; Rothauge, C.F.; Kraushaar, J.

    1979-01-01

    Surgical treatment of tumours of the bladder is still not generally accepted, and its results are unsatisfactory. To ameliorate this situation, the new energy source of laser is now being tested in transurethral treatment. There are several groups of scientists who study the use of lasers suited for human medicine: CO 2 laser (Tel Aviv), YAG neodymium laser (Munich), and argon laser (Giessen). In the urological university hospital at Giessen, where a human bladder carcinoma received laser treatment for the first time in the world in 1976, 45 argon laser operations on 38 patients are investigated. There were 37 bladder tumours of different stages and one haemangioma. Laser monotherapy was applied in 11 cases. The bulk of the cases, however, was treated by combined electro-laser-surgical treatment where the tumour bed and its immediate neighbourhood were irradiated after TUR. The results do not give a satisfactory answer as to the therapeutic value of laser. Advantages over TUR will probably be purely technical. (orig.) [de

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  20. Gynaecomastia: an unusual presenting symptom of bladder cancer.

    Science.gov (United States)

    Ahmed, Mashrafi; Kanji, Aleem; Begum, Tahmina

    2015-06-25

    A 74-year-old man presented to the outpatient clinic with painful gynaecomastia. A detailed physical examination to sort out possible causes of the gynaecomastia, including intracranial tumour, liver cirrhosis, hyperthyroidism, and adrenal and testicular tumour, was negative. No offending agent was found in his medication list. A CT scan of the head and ultrasound of the scrotum did not show any mass lesion. His serum β-human chorionic gonadotropin (β-hCG) and oestradiol levels were elevated. A CT scan of the abdomen and pelvis revealed bladder wall thickening with soft tissue mass. A cystoscopic biopsy confirmed transitional cell carcinoma with muscle invasion. The patient was started on chemotherapy but responded poorly. This case report describes the β-hCG and oestradiol-secreting transitional cell carcinoma of the bladder presenting as gynaecomastia in an older man. 2015 BMJ Publishing Group Ltd.

  1. Distinct pattern of p53 mutations in bladder cancer

    DEFF Research Database (Denmark)

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

    1993-01-01

    A distinct mutational spectrum for the p53 tumor suppressor gene in bladder carcinomas was established in patients with known exposures to cigarette smoke. Single-strand conformational polymorphism analysis of exons 5 through 8 of the p53 gene showed inactivating mutations in 16 of 40 (40%) bladder...... tumors from smokers and 13 of 40 (33%) tumors from lifetime nonsmokers. Overall, 13 of the 50 (26%) total point mutations discovered in this and previous work were G:C-->C:G transversions, a relatively rare mutational type in human tumors. In six tumors, identical AGA (Arg)-->ACA (Thr) point mutations...... double mutations, four of which were tandem mutations on the same allele. No double mutations were found in tumors from nonsmoking patients. None of the mutations in smokers were G:C-->T:A transversions, which would be anticipated for exposure to the suspected cigarette smoke carcinogen 4-aminobiphenyl...

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

    Science.gov (United States)

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

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

  3. Bladder pressure sensors in an animal model

    NARCIS (Netherlands)

    Koldewijn, E. L.; van Kerrebroeck, P. E.; Schaafsma, E.; Wijkstra, H.; Debruyne, F. M.; Brindley, G. S.

    1994-01-01

    Urinary incontinence due to detrusor hyperreflexia might be inhibited on demand if changes in bladder pressure could be detected by sensors and transferred into pudendal nerve electrostimulation. The aim of this study is to investigate how the bladder wall reacts on different sensor implants.

  4. NEOADJUVANT RADIOTHERAPY FOR BLADDER CARCINOMA IN ...

    African Journals Online (AJOL)

    Objective To evaluate the impact of preoperative accelerated hyperfractionated radiotherapy in the management of bladder carcinoma in Egyptian patients. Patients and Methods Between December 1996 and February 2000, 104 Egyptian patients with pathologically proven infiltrative bladder carcinoma were enrolled in ...

  5. Advances in immunotherapy for bladder cancer

    International Nuclear Information System (INIS)

    Zhao Jiyu; Chen Lijun

    2009-01-01

    The conventional treatments for bladder cancer, including surgery, chemotherapy and radiotherapy, are highly invasive and bring about lots of side effects. Immunotherapy has become a promising strategy for the treatment of malignant tumors. This review presents the research advances in immunotherapy of bladder cancer. (authors)

  6. Bladder exstrophy associated with complete urethral duplication ...

    African Journals Online (AJOL)

    J.E. Mensah

    ees.elsevier.com/afju · www.sciencedirect.com. Case report. Bladder exstrophy associated with complete urethral duplication: Bladder can be augmented with dorsal urethral mucosa. J.E. Mensaha,∗. , K.N. Ampadua, M.Y. Kyeia, B. Edusieb.

  7. Squamous cell carcinoma in bladder extrophy

    OpenAIRE

    Cabral-Ribeiro, J; Silva, C; Sousa, L; Pérez García, D; Ribeiro dos Santos, A

    2005-01-01

    Bladder extrophy is a rare congenital malformation that nowadays is surgically corrected in neonatal period. We present a case report of a 71-year-old male with a verrucous squamous cell carcinoma arising in a classical uncorrected form of bladder extrophy.

  8. 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

  9. Non-muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Malmström, Per-Uno; Agrawal, Sachin; Bläckberg, Mats

    2017-01-01

    The management of non-muscle-invasive bladder cancer (NMIBC) has evolved from the first reports on bladder endoscopy and transurethral resection to the introduction of adjuvant intravesical treatment. However, disease recurrence and progression remain an ongoing risk, placing a heavy burden...

  10. Bladder dysfunction in advanced Parkinson's disease

    DEFF Research Database (Denmark)

    Winge, Kristian; Nielsen, Kurt K

    2012-01-01

    Parkinson's disease (PD) patients often have lower urinary tract symptoms. Seventy-four percent of patients with early-to-moderate disease report more than one bladder disturbance symptom. Severe bladder symptoms are reported in 27-39% of PD patients. The aim of this study was to evaluate...

  11. Transient neuropathic bladder following herpes simplex genitalis.

    Science.gov (United States)

    Riehle, R A; Williams, J J

    1979-08-01

    A case of transient bladder dysfunction and urinary retention concomitant with herpes genitalis is presented. The protean manifestations of the herpes simplex virus, the similar neurotropic behavior of simplex and zoster, and the neurologic sequelae of the cutaneous simplex eruption are discussed. The possibility of sacral radiculopathy after herpes genitalis must be considered when evaluating acute or episodic neurogenic bladders.

  12. Neuropathic bladder in the neonate.

    Science.gov (United States)

    Carr, Michael C

    2014-09-01

    The management of infants born with myelomeningocele depends on understanding how their bladder stores and empties urine. Storage at low pressure with effective emptying periodically throughout the day is the goal. Intervention is designed to impact on one or both of these processes so that infants can remain infection-free and at the same time allow for appropriate renal growth over time. Urodynamic evaluation plays an important role, so that neonates can be stratified according to their risk. Most patients require intermittent catheterization and pharmacotherapy to achieve these goals at some point in their lives. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Xiangfei, Chai; Hulshof, Maarten; Bel, Arjan [Department of Radiotherapy, Academic medical Center, University of Amsterdam, 1105 AZ, Amsterdam (Netherlands); Van Herk, Marcel; Betgen, Anja [Department of Radiotherapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX, Amsterdam (Netherlands)

    2012-06-21

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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  16. PLK-1 Silencing in Bladder Cancer by siRNA Delivered With Exosomes.

    Science.gov (United States)

    Greco, Kristin A; Franzen, Carrie A; Foreman, Kimberly E; Flanigan, Robert C; Kuo, Paul C; Gupta, Gopal N

    2016-05-01

    To use exosomes as a vector to deliver small interfering ribonucleic acid (siRNA) to silence the polo-like kinase 1 (PLK-1) gene in bladder cancer cells. Exosomes were isolated from both human embryonic kidney 293 (HEK293) cell and mesenchymal stem cell (MSC) conditioned media. Fluorescently labeled exosomes were co-cultured with bladder cancer and normal epithelial cells and uptake was quantified by image cytometry. PLK-1 siRNA and negative control siRNA were loaded into HEK293 and MSC exosomes using electroporation. An invasive bladder cancer cell line (UMUC3) was co-cultured with the electroporated exosomes. Quantitative reverse transcriptase polymerase chain reaction was performed. Protein analysis was performed by Western blot. Annexin V staining and MTT assays were used to investigate effects on apoptosis and viability. Bladder cancer cell lines internalize an increased percentage of HEK293 exosomes when compared to normal bladder epithelial cells. Treatment of UMUC3 cells with exosomes electroporated with PLK-1 siRNA achieved successful knockdown of PLK-1 mRNA and protein when compared to cells treated with negative control exosomes. HEK293 and MSC exosomes were effectively used as a delivery vector to transport PLK-1 siRNA to bladder cancer cells in vitro, resulting in selective gene silencing of PLK-1. The use of exosomes as a delivery vector for potential intravesical therapy is attractive. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Possible distinct molecular carcinogenic pathways for bladder cancer in Ukraine, before and after the Chernobyl disaster.

    Science.gov (United States)

    Morimura, Keiichirou; Romanenko, Alina; Min, Wei; Salim, Elsayed I; Kinoshita, Anna; Wanibuchi, Hideki; Vozianov, Alexander; Fukushima, Shoji

    2004-04-01

    After the Chernobyl accident in 1986, the incidence of urinary bladder cancers in the Ukraine increased gradually from 26.2 to 43.3 per 100,000 people between 1986 and 2001. In the areas of low level but persistent cesium-137 (137Cs) radio-contamination, a unique atypical radiation-related urinary bladder cystitis named 'Chernobyl cystitis', a possible pre-neoplastic condition in humans, has been detected. We have previously documented high incidences of bladder lesions, including severe dysplasias and/or carcinoma in situ, in association with this cystitis and correlating with oxidative DNA damage. To further investigate the molecular mechanisms underlying bladder carcinogenesis with this specific etiology, mutation analysis of p53 gene (exon 5-8) was performed for 11 and 18 paraffin-embedded bladder cancers in Ukrainians, respectively collected before and after the Chernobyl disaster. DNAs were extracted and subjected to nested PCR-single-strand conformational polymorphism analysis followed by direct DNA sequencing, as well as p53 immunohistochemistry (IHC). The incidences of p53 gene mutation were 54.5 and 16.7% for before and after the Chernobyl disaster, respectively, the difference being statistically significant. Also a tendency for higher p53 IHC score was apparent in the earlier group of lesions. No significant difference was noted for the proportions of historical types. These results point to possible distinct molecular carcinogenic pathways of bladder cancer formation, before and after the Chernobyl disaster, on the basis of variation in p53 gene alteration.

  18. The supraspinal neural correlate of bladder cold sensation--an fMRI study.

    Science.gov (United States)

    Mehnert, Ulrich; Michels, Lars; Zempleni, Monika-Zita; Schurch, Brigitte; Kollias, Spyros

    2011-06-01

    In recent years, functional imaging studies have revealed a supraspinal network, which is involved in perception and processing of bladder distention. Very little information exists on the cortical representation of C-fiber transmitted temperature sensation of the human bladder, although C-fibers seem to be involved in the pathomechanisms of bladder dysfunctions. Our aim was, therefore, to evaluate the outcome of bladder cold stimulation on supraspinal activity using functional magnetic resonance imaging (fMRI). A block design fMRI study was performed in 14 healthy females at the MR-center of the University of Zurich. After catheterization, all subjects were investigated in a 3.0-Tesla Scanner. The scanning consisted of 10 repetitive cycles. Each cycle consisted of five conditions: REST, INFUSION, SENSATION, DRAIN 1, and DRAIN 2. Cold saline was passively infused at 4-8°C during scanning. Not more than 100 ml were infused per cycle. Blood-oxygen-level-dependent (BOLD) signal analysis of the different conditions was compared to REST. All activations were evaluated on a random effects level at P = 0.001. Activation of brain regions for bladder cold stimulation (DRAIN 1 period) was found bilaterally in the inferior parietal lobe [Brodmann area (BA) 40], the right insula (BA 13), the right cerebellar posterior lobe, the right middle temporal gyrus (BA 20), and the right postcentral gyrus (BA 3). In conclusion, bladder cooling caused a different supraspinal activation pattern compared to what is known to occur during bladder distention. This supports our hypothesis that cold sensation is processed differently from bladder distension at the supraspinal level. Copyright © 2010 Wiley-Liss, Inc.

  19. 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...

  20. Lymphoma of the Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Anthony Kodzo-Grey Venyo

    2014-01-01

    Full Text Available Background. Lymphoma of the urinary bladder (LUB is rare. Aims. To review the literature on LUB. Methods. Various internet databases were used. Results. LUB can be either primary or secondary. The tumour has female predominance; most cases occur in middle-age women. Secondary LUB occurs in 10% to 25% of leukemias/lymphomas and in advanced-stage systemic lymphoma. Less than 100 cases have been reported. MALT typically affects adults older than 60 years; 75% are female. Diffuse large B-cell lymphoma is also common and may arise from transformation of MALT. LUB presents with haematuria, dysuria, urinary frequency, nocturia, and abdominal or back pain. Macroscopic examination of LUBs show large discrete tumours centred in the dome or lateral walls of the bladder. Positive staining of LUB varies by the subtype of lymphoma; B-cell lymphomas are CD20 positive. MALT lymphoma is positively stained for CD20, CD19, and FMC7 and negatively stained for CD5, CD10, and CD11c. LUB stains negatively with Pan-keratin, vimentin, CK20, and CK7. MALT lymphoma exhibits t(11; 18(q21: 21. Radiotherapy is an effective treatment for the MALT type of LUB with no recurrence. Conclusions. LUB is diagnosed by its characteristic morphology and immunohistochemical characteristics. Radiotherapy is a useful treatment.

  1. Complex bladder-exstrophy-epispadias management: Causes of failure of initial bladder closure

    Directory of Open Access Journals (Sweden)

    Kouame Dibi Bertin

    2014-01-01

    Full Text Available The success of the initial closure of the complex bladder-exstrophy remains a challenge in pediatric surgery. This study describes a personal experience of the causes of failure of the initial closure and operative morbidity during the surgical treatment of bladder-exstrophy complex. From April 2000 to March 2014, four patients aged 16 days to 7 years and 5 months underwent complex exstrophy-epispadias repair with pelvic osteotomies. There were three males and one female. Three of them had posterior pelvic osteotomy, one had anterior innominate osteotomy. Bladder Closure: Bladder closure was performed in three layers. Our first patient had initial bladder closure with polyglactin 4/0 (Vicryl ® 4/0, concerning the last three patients, initial bladder closure was performed with polydioxanone 4/0 (PDS ® 4/0. The bladder was repaired leaving the urethral stent and ureteral stents for full urinary drainage for three patients. In one case, only urethral stent was left, ureteral drainage was not possible, because stents sizes were more important than the ureteral diameter. Out of a total of four patients, initial bladder closure was completely achieved for three patients. At the immediate postoperative follow-up, two patients presented a complete disunion of the abdominal wall and bladder despite an appropriate postoperative care. The absorbable braided silk (polyglactin used for the bladder closure was considered as the main factor in the failure of the bladder closure. The second cause of failure of the initial bladder closure was the incomplete urine drainage, ureteral catheterisation was not possible because the catheters sizes were too large compared with the diameters of the ureters. The failure of the initial bladder-exstrophy closure may be reduced by a closure with an absorbable monofilament silk and efficient urine drainage via ureteral catheterisation.

  2. Arsenate and dimethylarsinic acid in drinking water did not affect DNA damage repair in urinary bladder transitional cells or micronuclei in bone marrow

    Science.gov (United States)

    Arsenic is a recognized human skin, lung, and urinary bladder carcinogen, and may act as a cocarcinogen in the urinary bladder (with cigarette smoking) and skin (with UV light exposure). Possible modes of action of arsenic carcinogenesis/cocarcinogenesis include induction of DNA ...

  3. A Boy with a Large Bladder Stone

    Directory of Open Access Journals (Sweden)

    Kuo-Shen Chow

    2008-08-01

    Full Text Available Despite the frequent association of urinary tract infection with vesicoureteral reflux and urinary calculi, since vesicouretal reflux is induced by bladder stones, the coexistence of vesicoureteral reflux and bladder stones is rare. Because of its occurrence in children belonging to poor socioeconomic groups, it is believed to be a deficiency disorder. Most cases of bladder stones occur between the ages of 2 and 5 years. Common clinical presentations of bladder stones include urinary dribbling and enuresis, frequency of micturition, pain during micturition, pelvic pain and hematuria. We report the occurrence of a large bladder stone in a boy, who experienced intermittent lower abdominal pain and urinary incontinence, both during the day and at night. He had been diagnosed with enuresis and treated in pediatric clinics for 1 year. Delayed diagnosis resulted in bladder stone formation. The stone was larger than 2.5 cm and open vesicolithotomy was therefore selected as the best and safest treatment choice. His symptoms disappeared after surgery. Thorough metabolic and environmental evaluations of such cases are required on an individual basis. Bladder stones should be considered as a possible diagnosis in children presenting with urinary incontinence.

  4. Gall bladder function test with Ceruletid

    International Nuclear Information System (INIS)

    Schindler, G.

    1981-01-01

    Compared with the stimulating food given orally in the gall bladder function test the administration of the decapeptide Ceruletid which is related with Cholecystokinin has the advantage of avoiding resorption disturbances in the upper gastrointestinal tract. To 100 patients with positive peroral cholecystography, Ceruletid was injected i.m. in a dose of 0.4 μg/kg body weight. The contrasting of the main bile duct was thus increased from 10% to 86%. The oral stimulating food brings an increase to appr. 20%. A special importance is assigned to the frequent diagnosis of adenomyomatoses which, with 6%, lies significantly above the 0.8% achieved by means of the oral stimulating food. More contractile segments of the gall bladder wall can cause pain symptoms which are typical for the biliary tract. Adenomyomatoses in the region of the infundibulum of the gall bladder cause colicky pains and are, as generally accepted, an absolute indication for a surgical intervention. The finding of small gall bladder conrements is often connected with a strong diminution of the gall bladder in order to prevent the small concrements from being overlapped by the non-contrasting bladder bile. Therefore, the application of Ceruletid should be considered also within the frame of the intravenous cholegraphy, thinking of the large number of normal gall bladder findings which were obtained with the oral stimulating food as the only diagnostical help. (orig./MG) [de

  5. Arsenic and urinary bladder cell proliferation

    International Nuclear Information System (INIS)

    Luster, Michael I.; Simeonova, Petia P.

    2004-01-01

    Epidemiologic studies have demonstrated that a close association exists between the elevated levels of arsenic in drinking water and the incidence of certain cancers, including transitional cell carcinomas of the urinary bladder. We have employed in vitro and in vivo models to examine the effects of sodium arsenite on the urinary bladder epithelium. Mice exposed to 0.01% sodium arsenite in drinking water demonstrated hyperproliferation of the bladder uroepithelium within 4 weeks after initiating treatment. This occurred in the absence of amorphous precipitates and was accompanied by the accumulation of trivalent arsenite (iAs 3+ ), and to a lesser extent dimethylarsenic (DMA), arsenate (iAs 5+ ), and monomethylarsenic (MMA) in bladder tissue. In contrast to the bladder, urinary secretion was primarily in the form of DMA and MMA. Arsenic-induced cell proliferation in the bladder epithelium was correlated with activation of the MAP kinase pathway, leading to extracellular signal-regulated kinase (ERK) kinase activity, AP-1 activation, and expression of AP-1-associated genes involved in cell proliferation. Activation of the MAP kinase pathway involved both epidermal growth factor (EGF) receptor-dependent and -independent events, the latter involving Src activation. Studies summarized in this review suggest that arsenic accumulates in urinary bladder epithelium causing activation of specific signaling pathways that lead to chronic increased cell proliferation. This may play a non-epigenetic role in carcinogenesis by increasing the proliferation of initiated cells or increasing the mutational rate

  6. Urinary bladder cancer: role of MR imaging.

    Science.gov (United States)

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

    2012-01-01

    Urinary bladder cancer is a heterogeneous disease with a variety of pathologic features, cytogenetic characteristics, and natural histories. It is the fourth most common cancer in males and the tenth most common cancer in females. Urinary bladder cancer has a high recurrence rate, necessitating long-term surveillance after initial therapy. Early detection is important, since up to 47% of bladder cancer-related deaths may have been avoided. Conventional computed tomography (CT) and magnetic resonance (MR) imaging are only moderately accurate in the diagnosis and local staging of bladder cancer, with cystoscopy and pathologic staging remaining the standards of reference. However, the role of newer MR imaging sequences (eg, diffusion-weighted imaging) in the diagnosis and local staging of bladder cancer is still evolving. Substantial advances in MR imaging technology have made multiparametric MR imaging a feasible and reasonably accurate technique for the local staging of bladder cancer to optimize treatment. In addition, whole-body CT is the primary imaging technique for the detection of metastases in bladder cancer patients, especially those with disease that invades muscle. © RSNA, 2012.

  7. Experimental model of bladder instability in rabbits

    Directory of Open Access Journals (Sweden)

    Balasteghin K.T.

    2003-01-01

    Full Text Available OBJECTIVE: Propose a new experimental model of bladder instability in rabbits after partial bladder obstruction. MATERIALS AND METHODS: Thirty North Folk male rabbits, weighting 1,700 to 2,820 g (mean: 2,162 g were studied. The animals were distributed in 2 experimental groups, formed by 15 rabbits each: Group 1 - clinical control. In this group there was no surgical intervention; Group 2 - bladder outlet obstruction. In this group, after anesthetizing the animal, urethral cannulation with Foley catheter 10F was performed and then an adjustable plastic bracelet was passed around the bladder neck. It was then adjusted in order to not constrict the urethra. The following parameters were studied in M1 - pre-operative period; M2 - 4 weeks post-operatively moments: 1- urine culture; 2- cystometric study; 3- serum creatinine and BUN. RESULTS: Bladder weight was 2.5 times larger in the group with obstruction than in the control group. Cystometric evaluation showed a significant increase in maximal vesical volume in the final moment at Group G2. However, there was no statistically significant difference among the groups studied. There was no statistically significant difference between maximal detrusor pressure and vesical compliance in the different moments or in the studied groups. There was an absence of uninhibited detrusor contractions in all the animals in group 1, and involuntary contractions were detected in 93% of group 2 animals. There was no significant variation in BUN and serum creatinine either among the groups or in the same group. CONCLUSIONS: We observed in the group with obstruction a bladder weight 2.5 higher than normal bladders. We detected involuntary contractions in 93% of the animals in group 2, establishing this experimental model as appropriate to secondary bladder instability and partial bladder outlet obstruction.

  8. Clinical significance of the VEGF level in urinary bladder carcinoma.

    Science.gov (United States)

    Sankhwar, Monica; Sankhwar, Satya Narayan; Abhishek, Amar; Rajender, Singh

    2015-01-01

    To investigate the correlation of Vascular Endothelial Growth Factor (VEGF) and micro-vessel density (MVD) with urinary bladder tumor and its stage. The study was conducted between January 2010 and December 2012. The study included screening of 122 patients at elevated risk for bladder cancer, of which 35 patients were finally enrolled in the study. Diagnosis was made on the basis of urine cytology, radiological investigation (ultrasound KUB, and CT-scan) and histopathology. Thirty-five normal cancer-free individuals were enrolled as controls. Human VEGF levels were measured using an enzyme linked immunoassay and protein content (pg/mg protein) by Lowry method. SPSS for Windows version 10.0.7 (SPSS, Chicago, IL, USA) was used for statistical analysis of the data. Mean urine VEGF level in the cases was significantly higher in comparison to the control group. There was a direct correlation between VEGF level and tumor stage. Mean urine VEGF values were minimum in the control group (22.75 ± 15.41 pg/mg creatinine) and maximum in stage IV patients (180.15 ± 75.93 pg/mg creatinine). Tissue VEGF levels also showed a similar trend of increase with increase in stage. Urine VEGF level also showed a correlation with tissue VEGF level. Similarly, MVD showed a significant increase with increase in tumor stage. A correlation between bladder cancer and MVD and VEGF suggest that the latter can serve as markers for therapeutic guidance. This is the first study from India on clinical and pathological correlation among urine VEGF, tumor tissue VEGF levels, and Micro Vessel Density (MVD) in urinary bladder cancer patients.

  9. [Bladder-conserving treatment for bladder cancer: potential of and developments in radiotherapy].

    Science.gov (United States)

    Hulshof, Maarten C C M; Pieters, Bradley R; Koning, Caro C E

    2013-01-01

    The standard treatment for muscle-invasive bladder cancer is surgical removal of the bladder and construction of a neobladder. Recently, important improvements have been made in the potential for bladder-conserving treatment using radiotherapy. External beam radiotherapy has undergone technological improvements, as a result of which it is possible to radiate the tumour more precisely while decreasing radiation to healthy tissue. Radiochemotherapy improves local recurrence-free and overall survival compared with radiotherapy alone. The results of this combined treatment are comparable with those of surgery. Additionally, Dutch radiotherapy departments have collected data in a national database of 1040 selected patients with confined bladder cancer. These patients were treated with external beam radiation, limited surgery and brachytherapy. The 5-year local recurrence-free survival was 75%. Bladder conserving treatment options for muscle-invasive bladder cancer should be discussed during the multidisciplinary meeting.

  10. Near infrared imaging to identify sentinel lymph nodes in invasive urinary bladder cancer

    Science.gov (United States)

    Knapp, Deborah W.; Adams, Larry G.; Niles, Jacqueline D.; Lucroy, Michael D.; Ramos-Vara, Jose; Bonney, Patty L.; deGortari, Amalia E.; Frangioni, John V.

    2006-02-01

    Approximately 12,000 people are diagnosed with invasive transitional cell carcinoma of the urinary bladder (InvTCC) each year in the United States. Surgical removal of the bladder (cystectomy) and regional lymph node dissection are considered frontline therapy. Cystectomy causes extensive acute morbidity, and 50% of patients with InvTCC have occult metastases at the time of diagnosis. Better staging procedures for InvTCC are greatly needed. This study was performed to evaluate an intra-operative near infrared fluorescence imaging (NIRF) system (Frangioni laboratory) for identifying sentinel lymph nodes draining InvTCC. NIRF imaging was used to map lymph node drainage from specific quadrants of the urinary bladder in normal dogs and pigs, and to map lymph node drainage from naturally-occurring InvTCC in pet dogs where the disease closely mimics the human condition. Briefly, during surgery NIR fluorophores (human serum albumen-fluorophore complex, or quantum dots) were injected directly into the bladder wall, and fluorescence observed in lymphatics and regional nodes. Conditions studied to optimize the procedure including: type of fluorophore, depth of injection, volume of fluorophore injected, and degree of bladder distention at the time of injection. Optimal imaging occurred with very superficial injection of the fluorophore in the serosal surface of the moderately distended bladder. Considerable variability was noted from dog to dog in the pattern of lymph node drainage. NIR fluorescence was noted in lymph nodes with metastases in dogs with InvTCC. In conclusion, intra-operative NIRF imaging is a promising approach to improve sentinel lymph node mapping in invasive urinary bladder cancer.

  11. Urinary Bladder Leiomyosarcoma: Primary Surgical Treatment

    Directory of Open Access Journals (Sweden)

    Hakim Slaoui

    2014-07-01

    Full Text Available Cases of bladder leiomyosarcoma represent 0.1% of all nonurothelial tumors. We present a case report of a 73-year-old man who underwent a radical cystoprostatectomy for a high-grade bladder leiomyosarcoma with an ileal diversion. The patient recovered uneventfully and no surgical margins were verified in final pathology. Early follow-up at 3 months shows no signs of computed tomography recurrence and adequate adaptation to ileal diversion. Although bladder sarcomas were once thought to have a grim prognosis, recent studies suggest that adequate surgical treatment is able to achieve optimal cancer control outcomes.

  12. Bladder exstrophy: current management and postoperative imaging

    International Nuclear Information System (INIS)

    Pierre, Ketsia; Borer, Joseph; Phelps, Andrew; Chow, Jeanne S.

    2014-01-01

    Bladder exstrophy is a rare malformation characterized by an infra-umbilical abdominal wall defect, incomplete closure of the bladder with mucosa continuous with the abdominal wall, epispadias, and alterations in the pelvic bones and muscles. It is part of the exstrophy-epispadias complex, with cloacal exstrophy on the severe and epispadias on the mild ends of the spectrum. Bladder exstrophy is the most common of these entities and is more common in boys. The goal of this paper is to describe common methods of repair and to provide an imaging review of the postoperative appearances. (orig.)

  13. Bladder exstrophy: current management and postoperative imaging

    Energy Technology Data Exchange (ETDEWEB)

    Pierre, Ketsia [Boston Children' s Hospital, Department of Radiology, Boston, MA (United States); Borer, Joseph [Boston Children' s Hospital, Department of Urology, Boston, MA (United States); Phelps, Andrew [University of California, San Francisco, Department of Pediatric Radiology, San Francisco, CA (United States); Chow, Jeanne S. [Boston Children' s Hospital, Department of Radiology, Boston, MA (United States); Boston Children' s Hospital, Department of Urology, Boston, MA (United States)

    2014-07-15

    Bladder exstrophy is a rare malformation characterized by an infra-umbilical abdominal wall defect, incomplete closure of the bladder with mucosa continuous with the abdominal wall, epispadias, and alterations in the pelvic bones and muscles. It is part of the exstrophy-epispadias complex, with cloacal exstrophy on the severe and epispadias on the mild ends of the spectrum. Bladder exstrophy is the most common of these entities and is more common in boys. The goal of this paper is to describe common methods of repair and to provide an imaging review of the postoperative appearances. (orig.)

  14. Modelling Creep (Relaxation of the Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Zdravkovic Nebojsa

    2017-12-01

    Full Text Available We first present the results of an experiment in which the passive properties of the urinary bladder were investigated using strips of rabbit bladder. Under the assumption that the urinary bladder had orthopaedic characteristics, the strips were taken in the longitudinal and in the circumferential directions. The material was subjected to uniaxial tension, and stress-stretch curves were generated for various rates of deformation. We found that the rates did not have a significantly effect on the passive response of the material. Additionally, the stress-stretch dependence during relaxation of the material when exposed to isometric conditions was determined experimentally.

  15. Experimental electrical stimulation of the bladder using a new device

    DEFF Research Database (Denmark)

    Petersen, T.; Christiansen, P.; Nielsen, B.

    1986-01-01

    Repeated bladder contractions were evoked during a six month period in three unanaesthetized female minipigs by using unipolar carbon fiber electrodes embedded in the bladder wall adjacent to the ureterovesical junction. In contrast to bipolar and direct bladder muscle stimulation unipolar...... electrodes at each ureterovesical junction evoked bladder pressure increase similar to those produced in previous investigations in dogs. Sacral nerve stimulation of S2 evoked bladder contraction at a minimal current. Microscopic examination revealed no cellular reactions to the carbon fibers...

  16. Researchers studying alternative to bladder removal for bladder cancer patients | Center for Cancer Research

    Science.gov (United States)

    A new phase I clinical trial conducted by researchers at the Center for Cancer Research (CCR) is evaluating the safety and tolerability, or the degree to which any side effects can be tolerated by patients, of a two-drug combination as a potential alternative to bladder removal for bladder cancer patients. The trial targets patients with non-muscle invasive bladder cancer (NMIBC) whose cancers have stopped responding to traditional therapies. Read more...

  17. Correlation of gene expression with bladder capacity in interstitial cystitis/bladder pain syndrome.

    Science.gov (United States)

    Colaco, Marc; Koslov, David S; Keys, Tristan; Evans, Robert J; Badlani, Gopal H; Andersson, Karl-Erik; Walker, Stephen J

    2014-10-01

    Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression. Bladder biopsies from female subjects with interstitial cystitis/bladder pain syndrome and female controls without signs of the disease were collected and divided into those with normal and low anesthetized bladder capacity, respectively. Samples then underwent RNA extraction and microarray assay. Data generated by these assays were analyzed using Omics Explorer (Qlucore, Lund, Sweden), GeneSifter® Analysis Edition 4.0 and Ingenuity® Pathway Analysis to determine similarity among samples within and between groups, and measure differentially expressed transcripts unique to each phenotype. A total of 16 subjects were included in study. Principal component analysis and unsupervised hierarchical clustering showed clear separation between gene expression in tissues from subjects with low compared to normal bladder capacity. Gene expression in tissue from patients with interstitial cystitis/bladder pain syndrome who had normal bladder capacity did not significantly differ from that in controls without interstitial cystitis/bladder pain syndrome. Pairwise analysis revealed that pathways related to inflammatory and immune response were most involved. Microarray analysis provides insight into the potential pathological condition underlying interstitial cystitis/bladder pain syndrome. This pilot study shows that patients with this disorder who have low compared to normal bladder capacity have significantly different molecular characteristics, which may reflect a difference in disease pathophysiology. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc

  18. Bladder filling variation during conformal radiotherapy for rectal cancer

    International Nuclear Information System (INIS)

    Sithamparam, S; Ahmad, R; Sabarudin, A; Othman, Z; Ismail, M

    2017-01-01

    Conformal radiotherapy for rectal cancer is associated with small bowel toxicity mainly diarrhea. Treating patients with a full bladder is one of the practical solutions to reduce small bowel toxicity. Previous studies on prostate and cervix cancer patients revealed that maintaining consistent bladder volume throughout radiotherapy treatment is challenging. The aim of this study was to measure bladder volume variation throughout radiotherapy treatment. This study also measured the association between bladder volume changes and diarrhea. Twenty two rectal cancer patients were recruited prospectively. Patients were planned for treatment with full bladder following departmental bladder filling protocol and the planning bladder volume was measured during CT-simulation. During radiotherapy, the bladder volume was measured weekly using cone-beam computed tomography (CBCT) and compared to planning bladder volume. Incidence and severity of diarrhea were recorded during the weekly patient review. There was a negative time trend for bladder volume throughout five weeks treatment. The mean bladder volume decreased 18 % from 123 mL (SD 54 mL) during CT-simulation to 101 mL (SD 71 mL) on the 5th week of radiotherapy, but the decrease is not statistically significant. However, there was a large variation of bladder volume within each patient during treatment. This study showed an association between changes of bladder volume and diarrhea (P = 0.045). In conclusion bladder volume reduced throughout radiotherapy treatment for conformal radiotherapy for rectal cancer and there was a large variation of bladder volume within patients. (paper)

  19. Bladder filling variation during conformal radiotherapy for rectal cancer

    Science.gov (United States)

    Sithamparam, S.; Ahmad, R.; Sabarudin, A.; Othman, Z.; Ismail, M.

    2017-05-01

    Conformal radiotherapy for rectal cancer is associated with small bowel toxicity mainly diarrhea. Treating patients with a full bladder is one of the practical solutions to reduce small bowel toxicity. Previous studies on prostate and cervix cancer patients revealed that maintaining consistent bladder volume throughout radiotherapy treatment is challenging. The aim of this study was to measure bladder volume variation throughout radiotherapy treatment. This study also measured the association between bladder volume changes and diarrhea. Twenty two rectal cancer patients were recruited prospectively. Patients were planned for treatment with full bladder following departmental bladder filling protocol and the planning bladder volume was measured during CT-simulation. During radiotherapy, the bladder volume was measured weekly using cone-beam computed tomography (CBCT) and compared to planning bladder volume. Incidence and severity of diarrhea were recorded during the weekly patient review. There was a negative time trend for bladder volume throughout five weeks treatment. The mean bladder volume decreased 18 % from 123 mL (SD 54 mL) during CT-simulation to 101 mL (SD 71 mL) on the 5th week of radiotherapy, but the decrease is not statistically significant. However, there was a large variation of bladder volume within each patient during treatment. This study showed an association between changes of bladder volume and diarrhea (P = 0.045). In conclusion bladder volume reduced throughout radiotherapy treatment for conformal radiotherapy for rectal cancer and there was a large variation of bladder volume within patients.

  20. Influence of bladder and rectal volume on spatial variability of a bladder tumor during radical radiotherapy

    International Nuclear Information System (INIS)

    Pos, Floris J.; Koedooder, Kees; Hulshof, Maarten C.C.M.; Tienhoven, Geertjan van; Gonzalez Gonzalez, Dionisio

    2003-01-01

    Purpose: To assess the spatial variability of a bladder tumor relative to the planning target volume boundaries during radical radiotherapy, and furthermore to develop strategies to reduce spatial variability. Methods and Materials: Seventeen patients with solitary T2-T4N0M0 bladder cancer were treated with a technique delivering 40 Gy/2 Gy in 20 fractions to the whole bladder with a concomitant boost to the bladder tumor of 20 Gy in 1 Gy fractions in an overall time of 4 weeks. CT scans were made weekly, immediately after treatment, and matched with the planning CT scan. Spatial variability of the tumor, as well as bladder volume and rectal diameter, were scored for each patient each week. Results: In 65% of patients, a part of the tumor appeared outside the planning target volume boundaries at least one time during the course of radiotherapy. No consistent relation of this variability with time was found. Bladder volumes and rectal diameters showed marked variability during the course of treatment. A large initial bladder volume and rectal diameter predicted a large volume variation and a large tumor spatial variability. Conclusion: In this study, a margin of 1.5 to 2 cm seemed to be inadequate in 65% of the patients with respect to spatial variability. Bladder volume and rectal diameter were found to be predictive for spatial variability of a bladder tumor during concomitant boost radiotherapy

  1. Influence of bladder and rectal volume on spatial variability of a bladder tumor during radical radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Pos, Floris J; Koedooder, Kees; Hulshof, Maarten C.C.M.; Tienhoven, Geertjan van; Gonzalez Gonzalez, Dionisio

    2003-03-01

    Purpose: To assess the spatial variability of a bladder tumor relative to the planning target volume boundaries during radical radiotherapy, and furthermore to develop strategies to reduce spatial variability. Methods and Materials: Seventeen patients with solitary T2-T4N0M0 bladder cancer were treated with a technique delivering 40 Gy/2 Gy in 20 fractions to the whole bladder with a concomitant boost to the bladder tumor of 20 Gy in 1 Gy fractions in an overall time of 4 weeks. CT scans were made weekly, immediately after treatment, and matched with the planning CT scan. Spatial variability of the tumor, as well as bladder volume and rectal diameter, were scored for each patient each week. Results: In 65% of patients, a part of the tumor appeared outside the planning target volume boundaries at least one time during the course of radiotherapy. No consistent relation of this variability with time was found. Bladder volumes and rectal diameters showed marked variability during the course of treatment. A large initial bladder volume and rectal diameter predicted a large volume variation and a large tumor spatial variability. Conclusion: In this study, a margin of 1.5 to 2 cm seemed to be inadequate in 65% of the patients with respect to spatial variability. Bladder volume and rectal diameter were found to be predictive for spatial variability of a bladder tumor during concomitant boost radiotherapy.

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

    International Nuclear Information System (INIS)

    Stam, Marcel R.; Lin, Emile N.J. Th. van; Vight, Lisette P. van der; Kaanders, Johannes; Visser, Andries G.

    2006-01-01

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

  3. Double-negative feedback loop between long non-coding RNA TUG1 and miR-145 promotes epithelial to mesenchymal transition and radioresistance in human bladder cancer cells.

    Science.gov (United States)

    Tan, Jiemei; Qiu, Kaifeng; Li, Mingyi; Liang, Ying

    2015-10-07

    LncRNAs have a critical role in the regulation of cellular processes such as cancer progression and metastasis. In the present study, we confirmed that TUG1 was overexpressed in bladder cancer tissues and established cell lines. Knockdown of TUG1 inhibited bladder cancer cell metastasis both in vitro and in vivo. Furthermore, we found that TUG1 promoted cancer cell invasion and radioresistance through inducing epithelial-to-mesenchymal transition (EMT). Interestingly, TUG1 decreased the expression of miR-145 and there was a reciprocal repression between TUG1 and miR-145 in an Argonaute2-dependent manner. ZEB2 was identified as a down-stream target of miR-145 and TUG1 exerted its function through the miR-145/ZEB2 axis. In summary, our data indicated that blocking TUG1 function may be an effective anti-cancer therapy. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Knapp, Deborah W; Ramos-Vara, José A; Moore, George E; Dhawan, Deepika; Bonney, Patty L; Young, Kirsten E

    2014-01-01

    Each year more than 65,000 people are diagnosed with urinary bladder cancer, and more than 14,000 people die from the disease in the United States. Studies in relevant animal models are essential to improve the management of bladder cancer. Naturally occurring bladder cancer in dogs very closely mimics human invasive bladder cancer, specifically high-grade invasive transitional cell carcinoma (TCC; also referred to as invasive urothelial carcinoma) in cellular and molecular features; biological behavior, including sites and frequency of metastasis; and response to therapy. Canine bladder cancer complements experimentally induced rodent tumors in regard to animal models of bladder cancer. Results of cellular and molecular studies and -omics analyses in dogs are expected to lead to improved detection of TCC and preneoplastic lesions, earlier intervention, better prediction of patient outcome, and more effective TCC management overall. Studies in dogs are being used to help define heritable risks (through very strong breed-associated risk) and environment risks and to evaluate prevention and treatment approaches that benefit humans as well as dogs. Clinical treatment trials in pet dogs with TCC are considered a win-win scenario by clinician scientists and pet owners. The individual dog benefits from effective treatment, the results are expected to help other dogs, and the findings are expected to ultimately help humans with TCC. This article provides an overview of canine TCC, a summary of the similarities and differences between canine and human invasive TCC, and examples of the types of valuable translational research that can be done using dogs with naturally occurring TCC. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. Treatment Options by Stage (Bladder Cancer)

    Science.gov (United States)

    ... above the waist. Tiny tubules in the kidneys filter and clean the blood . They take out waste ... to bladder cancer. Being exposed to paints, dyes, metals, or petroleum products in the workplace. Past treatment ...

  6. Epidemiology of bladder cancer. A second look

    Energy Technology Data Exchange (ETDEWEB)

    Wynder, E.L.; Goldsmith, R.

    1977-09-01

    A case-control study among 574 male and 158 female bladder cancer patients and equal numbers of matched controls was conducted between 1969 and 1974 in 17 hospitals in six United States cities. We determined that cigarette smokers of both sexes were at higher relative risk than nonsmokers. Cigarette smoking was responsible for about one-half of male and one-third of female bladder cancer. There was an excess of bladder cancer patients with some previous occupational exposure, such as rubber, chemicals, and textiles. A weak association with coffee drinking, which appeared to be independent of smoking, was found for males. Users of artificial sweetners were not over-represented among the cases. The authors conclude that the epidemiologic pattern of bladder cancer cannot be fully accounted for by cigarette smoking and occupational exposure and suggest a series of metabolic studies to assess the role of additional factors, such as nutrition.

  7. 16. PRE-OPERATIVE BLADDER IRRIGATION

    African Journals Online (AJOL)

    Esem

    effectiveness of using preoperative bladder irrigation with 1% povidone iodine in reducing ... consenting patient who presented to the department of surgery for open ..... infections in a tertiary care center in south-western. Nigeria. International ...

  8. Conformal radiotherapy of urinary bladder cancer

    International Nuclear Information System (INIS)

    Muren, Ludvig Paul; Smaaland, Rune; Dahl, Olav

    2004-01-01

    Recent advances in radiotherapy (RT) are founded on the enhanced tumour visualisation capabilities of new imaging modalities and the precise deposition of individualised radiation dose distributions made possible with the new systems for RT planning and delivery. These techniques have a large potential to also improve the results of RT of urinary bladder cancer. Major challenges to take full advantage of these advances in the management of bladder cancer are to control, and, as far as possible, reduce bladder motion, and to reliably account for the related intestine and rectum motion. If these obstacles are overcome, it should be possible in the near future to offer selected patients with muscle invading bladder cancer an organ-sparing, yet effective combined-modality treatment as an alternative to radical surgery

  9. Screening for Bladder and Other Urothelial Cancers

    Science.gov (United States)

    ... cancer is the focus of this summary. Enlarge Anatomy of the male urinary system (left panel) and female urinary system (right panel) showing the kidneys, ureters, bladder, and urethra. Urine is made in ...

  10. Clinical observation of radiation urinary bladder disease

    International Nuclear Information System (INIS)

    Jin Yuke; Liu Libo; Zhang Haiying; Liang Shuo; Chen Dawei; Wu Zhenfeng; Dong Lihua; Lu Xuejun

    2004-01-01

    Objective: Clinical characteristic, diagnosis and treatment of radiation urinary bladder disease induced by radiation therapy for cancers in the pelvis were inquired into for providing diagnostic basis. Methods: Statistical analysis for the clinical cases was carried out. Results: The incidence of radiation bladder diseases induced by radiation therapy of cervix cancer are about 0.8%-2.96%, with an average of 2.14%. Radiation bladder disease is divided into acute radiation cystitis, chronic radiation cystitis and radiation vesical fistula. Chronic radiation cystitis is seen most often in the clinic and its main clinical symptom is painless macroscopic hematuria, which is again subdivided into slight and severe degrees. Diagnosis should include history of exposure to radiation, which dose exceed the dose threshold, and typical clinical characteristics. Conclusion: The characteristics, types and diagnostic basis of radiation urinary bladder disease analyzed in this study can provide the reference for drawing up diagnostic standard

  11. Integrated irradiation and cystectomy for bladder cancer

    International Nuclear Information System (INIS)

    Whitmore, W.F. Jr.

    1980-01-01

    Planned pre-operative irradiation and cystectomy for selected patients with bladder cancer was initiated approximately 20 years ago by a number of centres on the basis of the disappointing end results of treatment of bladder cancer by either irradiation or surgery and the empirical hope that the combination might lead to better results. This is a brief review of the logical basis for integrated treatment and of the Memorial Sloan-Kettering Cancer Center (MSKCC) experience with such therapy. (author)

  12. Androgen Receptor Signaling in Bladder Cancer

    OpenAIRE

    Li, Peng; Chen, Jinbo; Miyamoto, Hiroshi

    2017-01-01

    Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific differences in bladder cancer. This review summarizes and discusses the available data, suggesting the involvement of androgens and/or the androgen receptor pathways in u...

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

    International Nuclear Information System (INIS)

    Negraes, Priscilla D; Favaro, Francine P; Camargo, João Lauro V; Oliveira, Maria Luiza CS; Goldberg, José; Rainho, Cláudia A; Salvadori, Daisy MF

    2008-01-01

    Epigenetic alterations are a hallmark of human cancer. In this study, we aimed to investigate whether aberrant DNA methylation of cancer-associated genes is related to urinary bladder cancer recurrence. A set of 4 genes, including CDH1 (E-cadherin), SFN (stratifin), RARB (retinoic acid receptor, beta) and RASSF1A (Ras association (RalGDS/AF-6) domain family 1), had their methylation patterns evaluated by MSP (Methylation-Specific Polymerase Chain Reaction) analysis in 49 fresh urinary bladder carcinoma tissues (including 14 cases paired with adjacent normal bladder epithelium, 3 squamous cell carcinomas and 2 adenocarcinomas) and 24 cell sediment samples from bladder washings of patients classified as cancer-free by cytological analysis (control group). A third set of samples included 39 archived tumor fragments and 23 matched washouts from 20 urinary bladder cancer patients in post-surgical monitoring. After genomic DNA isolation and sodium bisulfite modification, methylation patterns were determined and correlated with standard clinic-histopathological parameters. CDH1 and SFN genes were methylated at high frequencies in bladder cancer as well as in paired normal adjacent tissue and exfoliated cells from cancer-free patients. Although no statistically significant differences were found between RARB and RASSF1A methylation and the clinical and histopathological parameters in bladder cancer, a sensitivity of 95% and a specificity of 71% were observed for RARB methylation (Fisher's Exact test (p < 0.0001; OR = 48.89) and, 58% and 17% (p < 0.05; OR = 0.29) for RASSF1A gene, respectively, in relation to the control group. Indistinct DNA hypermethylation of CDH1 and SFN genes between tumoral and normal urinary bladder samples suggests that these epigenetic features are not suitable biomarkers for urinary bladder cancer. However, RARB and RASSF1A gene methylation appears to be an initial event in urinary bladder carcinogenesis and should be considered as defining a

  14. Complications of bladder distension during retrograde urethrography.

    Science.gov (United States)

    Barsanti, J A; Crowell, W; Losonsky, J; Talkington, F D

    1981-05-01

    A severe, ulcerative cystitis that resulted in macroscopic hematuria occurred in 8 of 20 healthy dogs undergoing a series of diagnostic tests. Four of the remaining 12 dogs had mild bladder lesions consisting of submucosal edema and hemorrhage. Nine of the 20 dogs developed urinary tract infection after the procedures. These complications seemed associated with the radiographic technique of retrograde urethrography performed when the urinary bladder was distended. To test this hypothesis, retrograde urethrography was performed on 5 additional dogs. With the bladder undistended, no complications occurred. However, distention of these same dogs' bladders for 1 minute or less with sterile lactated Ringer's solution administered through a Foley catheter in the penile urethra resulted in a macroscopic hematuria in all 5 dogs which persisted for 24 hours. A microscopic hematuria continued for 5 days. One dog developed a bacterial urinary tract infection. A severe fibrinopurulent cystitis was present at necropsy of 2 dogs 2 days after distention. The morphologic changes in the bladder gradually diminished over 7 days, but mild submucosal edema and hemorrhage were still present when 2 dogs were necropsied, 7 days after distention. These studies indicated that retrograde urethrography in dogs may be complicated by hemorrhagic cystitis and urinary tract infection if performed with urinary bladder distention.

  15. Laparoscopic hernia repair and bladder injury.

    Science.gov (United States)

    Dalessandri, K M; Bhoyrul, S; Mulvihill, S J

    2001-01-01

    Bladder injury is a complication of laparoscopic surgery with a reported incidence in the general surgery literature of 0.5% and in the gynecology literature of 2%. We describe how to recognize and treat the injury and how to avoid the problem. We report two cases of bladder injury repaired with a General Surgical Interventions (GSI) trocar and a balloon device used for laparoscopic extraperitoneal inguinal hernia repair. One patient had a prior appendectomy; the other had a prior midline incision from a suprapubic prostatectomy. We repaired the bladder injury, and the patients made a good recovery. When using the obturator and balloon device, it is important to stay anterior to the preperitoneal space and bladder. Prior lower abdominal surgery can be considered a relative contraindication to extraperitoneal laparoscopic hernia repair. Signs of gas in the Foley bag or hematuria should alert the surgeon to a bladder injury. A one- or two-layer repair of the bladder injury can be performed either laparoscopically or openly and is recommended for a visible injury. Mesh repair of the hernia can be completed provided no evidence exists of urinary tract infection. A Foley catheter is placed until healing occurs.

  16. Virtual computed tomography cystoscopy in bladder pathologies

    International Nuclear Information System (INIS)

    Arslan, Halil; Ceylan, Kadir; Harman, Mustafa; Yilmaz, Yuksel; Temizoz, Osman; Can, Saban

    2006-01-01

    Objective: assessed the usefulness of virtual cystoscopy performed with multidetector computed tomography (CT) in patients with different urinary bladder pathologies compared to the conventional cystoscopy.Materials and methods: eighteen patients with different bladder pathologies, which consisted of 11 tumors, 3 diverticula, 2 trabecular changes and 2 stones, were assessed with conventional cystoscopy and virtual CT cystoscopy. The results of virtual CT cystoscopy were compared with the findings of conventional cystoscopy. We determined the detection rate and positive predictive value of CT imaging based virtual cystoscopy in the diagnosis of urinary bladder lesions. Results: CT scanning was well tolerated by all patients, and no complications occurred. Images in 16 (88%) of the 18 virtual cystoscopic examinations were either of excellent or good quality. All tumors except one, 2 trabecular changes and 2 stones were characterized with similar findings in the both of methods. The masses ranged from 0.4 to 7.0 cm in diameter. While conventional cystoscopy could not evaluate interior part of the diverticulum, virtual CT cystoscopy could demonstrate clearly within it. There were no false-positive findings in our series. Conclusion: virtual CT cystoscopy is a promising technique to be used in the detection of bladder lesions. It should be considered especially at the evaluation of bladder diverticula. In the future, it may be possible or even advantageous to incorporate into the imaging algorithm for evaluation of bladder lesion. (author)

  17. Neo bladder long term follow-up

    International Nuclear Information System (INIS)

    Fakhr, I.; Mohamed, A. M.; Moustafa, A.; Al-Sherbiny, M.; Salama, M.

    2013-01-01

    One of the commonest forms of orthotopic bladder substitution for bladder cancer surivors, used in our institute, is the use of ileocecal segment. Sometimes, the need for Indiana pouch heterotropic continent diversion arises. Aim: To compare the long-term effect of orthotopic ileocecal bladder and heterotropic Indiana pouch following radical cystectomy in bladder cancer patients. Patients and methods: Between January 2008 and December 2011, 91 patients underwent radical cystectomy/anterior pelvic exentration and ortho topic ileocecal bladder reconstruction (61 patients) and Indiana pouch (30 patients), when orthotopic diversion could not be technically or oncologically feasible. Results: Convalescence was uneventful in most patients. All minor and major urinary leakage cases, in both diversions groups, where successfully conservatively treated. Only one patient in the ileocecal group with major urinary leak required re-exploration with successful revision of uretro-colonic anastomosis. Only one patient in the Indiana pouch group had accidentally discovered sub-centimetric stone, which was simply expelled. The overall survival proportion of ileocecal group was 100% compared to 80% in the Indiana pouch group (p < 0.001). The disease free survival proportion of ileocecal group was 90.8% compared to 80% in the Indiana pouch group (p = 0.076). Effective comparative daytime and nighttime urinary continence as well as renal function deterioration were not statistically significant between both reconstruction types. Conclusion: Both ileocecal bladder and Indiana pouch are safe procedures in regard to long-term effects over kidney function following radical cystectomy

  18. Increased Bladder Wall Thickness in Diabetic and Nondiabetic Women With Overactive Bladder

    Directory of Open Access Journals (Sweden)

    Hakkı Uzun

    2013-06-01

    Full Text Available Purpose: Bladder wall thickness has been reported to be associated with overactive bladder (OAB in women. Diabetic women have an increased risk for OAB syndrome and may have an increased risk for bladder wall thickness. Methods: A total of 235 female patients aged 40 to 75 years were categorized into four groups. The first group consisted of women free of urgency or urge urinary incontinence. The second group included nondiabetic women with idiopathic OAB. The third group consisted of women with diabetes and clinical OAB, and women with diabetes but without OAB constituted the fourth group. Bladder wall thickness at the anterior wall was measured by ultrasound by the suprapubic approach with bladder filling over 250 mL. Results: The diabetic (third group and nondiabetic (second group women with OAB had significantly greater bladder wall thickness at the anterior bladder wall than did the controls. However, the difference was not significant between the diabetic (third group and the nondiabetic (second group women with OAB. Women with diabetes but without OAB (fourth group had greater bladder wall thickness than did the controls but this difference was not significant. Additionally, the difference in bladder wall thickness between diabetic women with (third group and without (fourth group OAB was not significant. Conclusions: This is the first study to show that bladder wall thickness is increased in diabetic women with and without OAB. Additionally, nondiabetic women with OAB had increased bladder wall thickness. Further studies may provide additional information for diabetic and nondiabetic women with OAB, in whom the etiopathogenesis of the disease may be similar.

  19. Selective bladder preservation with curative intent for muscle-invasive bladder cancer. A contemporary review

    International Nuclear Information System (INIS)

    Koga, Fumitaka; Kihara, Kazunori

    2012-01-01

    Radical cystectomy plus urinary diversion, the reference standard treatment for muscle-invasive bladder cancer, associates with high complication rates and compromises quality of life as a result of long-term effects on urinary, gastrointestinal and sexual function, and changes in body image. As a society ages, the number of elderly patients unfit for radical cystectomy as a result of comorbidity will increase, and thus the demand for bladder-sparing approaches for muscle-invasive bladder cancer will also inevitably increase. Trimodality bladder-sparing approaches consisting of transurethral resection, chemotherapy and radiotherapy (Σ55-65 Gy) yield overall survival rates comparable with those of radical cystectomy series (50-70% at 5 years), while preserving the native bladder in 40-60% of muscle-invasive bladder cancer patients, contributing to an improvement in quality of life for such patients. Limitations of the trimodality therapy include muscle-invasive bladder cancer recurrence in the preserved bladder, which most often arises in the original muscle-invasive bladder cancer site; potential lack of curative intervention for regional lymph nodes; and increased morbidity in the event of salvage radical cystectomy for remaining or recurrent disease as a result of high-dose pelvic irradiation. Consolidative partial cystectomy with pelvic lymph node dissection followed by induction chemoradiotherapy at lower dose (exempli gratia (e.g.) 40 Gy) is a rational strategy for overcoming such limitations by strengthening locoregional control and reducing radiation dosage. Molecular profiling of the tumor and functional imaging might play important roles in optimal patient selection for bladder preservation. Refinement of radiation techniques, intensified concurrent or adjuvant chemotherapy, and novel sensitizers, including molecular targeting agent, are also expected to improve outcomes and consequently provide more muscle-invasive bladder cancer patients with favorable

  20. The role of imaging in pediatric bladder augmentation

    Energy Technology Data Exchange (ETDEWEB)

    Breen, Micheal; Chow, Jeanne S. [Boston Children' s Hospital, Department of Radiology, Boston, MA (United States); Phelps, Andrew [UCSF Benioff Children' s Hospital San Francisco, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Estrada, Carlos [Boston Children' s Hospital, Department of Urology, Boston, MA (United States)

    2015-09-15

    Bladder augmentation (also called augmentation cystoplasty) refers to a number of surgical methods that increase the capacity and compliance of the urinary bladder. Imaging has an important role in the postoperative evaluation of bladder augmentation. The most common augmentation procedures utilize enteric segments to augment the bladder. The various types of bladder augmentation have characteristic appearances on different imaging modalities. Spontaneous bladder perforation is a complication that is seen in both early and late post-operative periods and it is one of the most important complications for radiologists to be aware of as it is life-threatening. We review the indications for bladder augmentation in children, the surgical techniques employed, the normal postoperative appearances on imaging studies and the role of imaging complications of bladder augmentation including delayed spontaneous bladder rupture, which is life-threatening. (orig.)

  1. Long noncoding RNA in prostate, bladder, and kidney cancer.

    Science.gov (United States)

    Martens-Uzunova, Elena S; Böttcher, René; Croce, Carlo M; Jenster, Guido; Visakorpi, Tapio; Calin, George A

    2014-06-01

    Genomic regions without protein-coding potential give rise to millions of protein-noncoding RNA transcripts (noncoding RNA) that participate in virtually all cellular processes. Research over the last 10 yr has accumulated evidence that long noncoding RNAs (lncRNAs) are often altered in human urologic cancers. To review current progress in the biology and implication of lncRNAs associated with prostate, bladder, and kidney cancer. The PubMed database was searched for articles in the English language with combinations of the Medical Subject Headings terms long non coding RNA, long noncoding RNA, long untranslated RNA, cancer, neoplasms, prostate, bladder, and kidney. We summarise existing knowledge on the systematics, biology, and function of lncRNAs, particularly these involved in prostate, kidney, and bladder cancer. We also discuss the possible utilisation of lncRNAs as novel biomarkers and potential therapeutic targets in urologic malignancies and portray the major challenges and future perspectives of ongoing lncRNA research. LncRNAs are important regulators of gene expression interacting with the major pathways of cell growth, proliferation, differentiation, and survival. Alterations in the function of lncRNAs promote tumour formation, progression, and metastasis of prostate, bladder, and kidney cancer. LncRNAs can be used as noninvasive tumour markers in urologic malignancies. Increased knowledge of the molecular mechanisms by which lncRNAs perform their function in the normal and malignant cell will lead to a better understanding of tumour biology and could provide novel therapeutic targets for the treatment of urologic cancers. In this paper we reviewed current knowledge of long noncoding RNAs (lncRNAs) for the detection and treatment of urologic cancers. We conclude that lncRNAs can be used as novel biomarkers in prostate, kidney, or bladder cancer. LncRNAs hold promise as future therapeutic targets, but more research is needed to gain a better

  2. Finite element based bladder modeling for image-guided radiotherapy of bladder cancer

    NARCIS (Netherlands)

    Chai, Xiangfei; van Herk, Marcel; van de Kamer, Jeroen B.; Hulshof, Maarten C. C. M.; Remeijer, Peter; Lotz, Heidi T.; Bel, Arjan

    2011-01-01

    Purpose: A biomechanical model was constructed to give insight into pelvic organ motion as a result of bladder filling changes. Methods: The authors used finite element (FE) modeling to simulate bladder wall deformation caused by urine inflow. For ten volunteers, a series of MRI scans of the pelvic

  3. Can we improve transurethral resection of the bladder tumour for nonmuscle invasive bladder cancer?

    NARCIS (Netherlands)

    Liem, Esmee Iml; de Reijke, Theo M.

    2017-01-01

    Purpose of review The recurrence rate in patients with nonmuscle invasive bladder cancer is high, and the quality of transurethral resection of the bladder (TURB) tumour influences recurrence risk. We review new methods that aim to improve the effectiveness of TURB, and highlight studies of the past

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  5. An unusual double fungal infection of the bladder due to Candida ...

    African Journals Online (AJOL)

    G.V. KandaSwamy

    rarely pathogenic to humans, but may cause skin lesions, keratitis, onychomycosis, sinusitis and pulmonary infections [2]. Candida infection is synonymous with fungal cystitis, but cladosporium involving the bladder has virtually been unheard of. Case report. A 37-year-old diabetic female, mother of one child, presented with ...

  6. Discussion on the influence of HER2 status on the clinical outcome of bladder cancer continues

    NARCIS (Netherlands)

    Lammers, R.; Witjes, J.A.

    2011-01-01

    Evaluation of: Bolenz C, Shariat SF, Karakiewicz PI et al. Human epidermal growth factor receptor 2 expression status provides independent prognostic information in patients with urothelial carcinoma of the urinary bladder. BJUI 106, 1216-1222 (2010). The article under evaluation by Bolenz et al.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    : The correlation between the relative bladder volume (RBV, defined as repeat scan volume/planning scan volume) and the margins required to account for internal motion was first studied using a series of 20 bladder cancer patients with weekly repeat CT scanning during treatment. Both conformal RT (CRT) and IGRT......BACKGROUND AND PURPOSE: To control and account for bladder motion is a major challenge in radiotherapy (RT) of bladder cancer. This study investigates the relation between bladder volume variation and margins in conformal and image-guided RT (IGRT) for this disease. MATERIALS AND METHODS...... these patients were given fluid intake restrictions on alternating weeks during treatment. RESULTS: IGRT gave the strongest correlation between the RBV and margin size (R(2)=0.75; p10mm were required in only 1% of the situations when the RBV1, whereas isotropic margins >10...

  8. Work Capacity of the Bladder During Voiding: A Novel Method to Evaluate Bladder Contractile Function and Bladder Outlet Obstruction

    Directory of Open Access Journals (Sweden)

    Ning Liu

    2015-01-01

    Full Text Available Background: Work in voiding (WIV of the bladder may be used to evaluate bladder status throughout urination rather than at a single time point. Few studies, however, have assessed WIV owing to the complexity of its calculations. We have developed a method of calculating work capacity of the bladder while voiding and analyzed the associations of bladder work parameters with bladder contractile function and bladder outlet obstruction (BOO. Methods: The study retrospectively evaluated 160 men and 23 women, aged >40 years and with a detrusor pressure at maximal flow rate (P det Q max of ≥40 cmH 2 O in men, who underwent urodynamic testing. The bladder power integration method was used to calculate WIV; WIV per second (WIV/t and WIV per liter of urine voided (WIV/v were also calculated. In men, the relationships between these work capacity parameters and P det Q max and Abrams-Griffiths (AG number were determined using linear-by-linear association tests, and relationships between work capacity parameters and BOO grade were investigated using Spearman′s association test. Results: The mean WIV was 1.15 ± 0.78 J and 1.30 ± 0.88 J, mean WIV/t was 22.95 ± 14.45 mW and 23.78 ± 17.02 mW, and mean WIV/v was 5.59 ± 2.32 J/L and 2.83 ± 1.87 J/L in men and women, respectively. In men, WIV/v showed significant positive associations with P det Q max (r = 0.845, P = 0.000, AG number (r = 0.814, P = 0.000, and Schafer class (r = 0.726, P = 0.000. Conversely, WIV and WIV/t showed no associations with P det Q max or AG number. In patients with BOO (Schafer class > II, WIV/v correlated positively with increasing BOO grade. Conclusions: WIV can be calculated from simple urodynamic parameters using the bladder power integration method. WIV/v may be a marker of BOO grade, and the bladder contractile function can be evaluated by WIV and WIV/t.

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

    International Nuclear Information System (INIS)

    Seidl, Christof; Pfost, Birgit; Müller, Felix

    2013-01-01

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

  10. Neurogenic Bladder in Lyme Disease

    Directory of Open Access Journals (Sweden)

    Mi-hwa Kim

    2012-12-01

    Full Text Available Lyme disease is a multi-systemic, tick-borne infectious disease caused by a spirochete, Borrelia burgdorferi. Various urologic symptoms are associated with Lyme disease, which can be primary or late manifestations of the disease. Although voiding dysfunction is a rarely reported symptom in patients with Lyme disease, it is one of the most disabling complications of Lyme disease. Korea is not an endemic area of Lyme disease, thus, fewer cases have been reported. Herein, we report a case of a 32-year-old man with rapidly progressive bilateral ptosis, dysphagia, spastic paraparesis, and voiding difficulty in whom Lyme disease was diagnosed through serologic tests for antibodies and Western blot testing. A urodynamic study demonstrated detrusor areflexia and bulbocavernosus reflex tests showed delayed latency, indicating demyelination at S2-S4 levels. He received a 4-week course of intravenous ceftriaxone (2 g/day. The patient has recovered from the bilateral ptosis and spastic paraparesis but still suffers from neurogenic bladder.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  12. Muscarinic Acetylcholine Receptor M3 Mutation Causes Urinary Bladder Disease and a Prune-Belly-like Syndrome.

    Science.gov (United States)

    Weber, Stefanie; Thiele, Holger; Mir, Sevgi; Toliat, Mohammad Reza; Sozeri, Betül; Reutter, Heiko; Draaken, Markus; Ludwig, Michael; Altmüller, Janine; Frommolt, Peter; Stuart, Helen M; Ranjzad, Parisa; Hanley, Neil A; Jennings, Rachel; Newman, William G; Wilcox, Duncan T; Thiel, Uwe; Schlingmann, Karl Peter; Beetz, Rolf; Hoyer, Peter F; Konrad, Martin; Schaefer, Franz; Nürnberg, Peter; Woolf, Adrian S

    2011-11-11

    Urinary bladder malformations associated with bladder outlet obstruction are a frequent cause of progressive renal failure in children. We here describe a muscarinic acetylcholine receptor M3 (CHRM3) (1q41-q44) homozygous frameshift mutation in familial congenital bladder malformation associated with a prune-belly-like syndrome, defining an isolated gene defect underlying this sometimes devastating disease. CHRM3 encodes the M3 muscarinic acetylcholine receptor, which we show is present in developing renal epithelia and bladder muscle. These observations may imply that M3 has a role beyond its known contribution to detrusor contractions. This Mendelian disease caused by a muscarinic acetylcholine receptor mutation strikingly phenocopies Chrm3 null mutant mice. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  13. Chromium in urothelial carcinoma of the bladder.

    Science.gov (United States)

    Golabek, Tomasz; Socha, Katarzyna; Kudelski, Jacek; Darewicz, Barbara; Markiewicz-Zukowska, Renata; Chlosta, Piotr; Borawska, Maria

    2017-12-23

    Many epidemiological and experimental studies report a strong role of chemical carcinogens in the etiology of bladder cancer. However, the involvement of heavy metals in tumourigenesis of urothelial carcinoma of the bladder has been poorly investigated. Therefore, the aim of this study was to examine the relationship between chromium (Cr) and bladder cancer. Chromium concentration in two 36-sample series of bladder cancer tissue and sera from patients with this neoplasm were matched with those of a control group. The amount of trace elements in every tissue sample was determined using atomic absorption spectrometry. This was correlated with tumour stage. While the median chromium concentration levels reached statistically higher values in the bladder cancer tissue, compared with the non-cancer tissue (99.632ng/g and 33.144ng/g, respectively; p<0.001), the median Cr levels in the sera of the patients with this carcinoma showed no statistical difference when compared to those of the control group (0.511μg/l and 0.710μg/l, respectively; p=0.408). The median levels of Cr in the bladder tissue, depending on the stage of the tumour, compared with the tissue without the neoplasm, observed the same relationship for both non-muscle invasive and muscle-invasive tumours (p<0.001 and p<0.01, respectively). This study shows that patients with urothelial carcinoma of the bladder had higher tissue Cr levels than people without tumour, while no difference was found in the Cr serum levels between the two groups of patients under investigation.

  14. A case-control study on the association between bladder cancer and prior bladder calculus.

    Science.gov (United States)

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

    2013-03-15

    Bladder calculus is associated with chronic irritation and inflammation. As there is substantial documentation that inflammation can play a direct role in carcinogenesis, to date the relationship between stone formation and bladder cancer (BC) remains unclear. This study aimed to examine the association between BC and prior bladder calculus using a population-based dataset. This case-control study included 2,086 cases who had received their first-time diagnosis of BC between 2001 and 2009 and 10,430 randomly selected controls without BC. Conditional logistic regressions were employed to explore the association between BC and having been previously diagnosed with bladder calculus. Of the sampled subjects, bladder calculus was found in 71 (3.4%) cases and 105 (1.1%) controls. Conditional logistic regression analysis revealed that the odds ratio (OR) of having been diagnosed with bladder calculus before the index date for cases was 3.42 (95% CI = 2.48-4.72) when compared with controls after adjusting for monthly income, geographic region, hypertension, diabetes, coronary heart disease, and renal disease, tobacco use disorder, obesity, alcohol abuse, and schistosomiasis, bladder outlet obstruction, and urinary tract infection. We further analyzed according to sex and found that among males, the OR of having been previously diagnosed with