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Sample records for human bladder carcinoma

  1. 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.

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

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    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.

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

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    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.

  4. 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.

  5. 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

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

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    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.

  7. 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

  8. 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 ...

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

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    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.

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

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    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

  11. Squamous cell carcinoma in bladder extrophy

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    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.

  12. 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.

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

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    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

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

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    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.

  15. Chromium in urothelial carcinoma of the bladder.

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    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.

  16. SOX4 expression in bladder carcinoma

    DEFF Research Database (Denmark)

    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...

  17. 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

  18. Carcinoma of the bladder - the present situation

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    Backhouse, T W [9050155GB:Coventry and Warwickshire Hospital (UK). Dept. of Radiotherapy and Oncology

    1979-04-01

    Occupational exposure to carcinogens can result in the development of malignancies after a latent period as long as 45 years. New cases are therefore still being detected, although known carcinogens have been banned for some 30 years. Presenting symptoms, investigative techniques, types of bladder carcinoma and methods of spread are all discussed. Criteria for treatment selection are based on the stage of development of the tumor. Radiotherapy requires preliminary localization of the bladder in relation to external marks. A mercury-filled balloon is carefully positioned in the bladder at the internal meatus, and fluoroscopy provides films which are used in final calculations of dose distribution. A dose of 6000 rad is given by a 300 deg rotational technique over 6 weeks to the tumor volume contained within the 90% isodose curves. The advantages of the technique are discussed, and survival rates given for different tumors at various stages of development.

  19. Carcinoma Gall Bladder: Past, Present, and Future

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    Ghosh Y

    2014-12-01

    Full Text Available Carcinoma gall bladder is a very aggressive disease with poor outcomes. Despite achievements in the field of advanced imaging techniques, there is a very high mortality rate of the disease Cancer is the second most common disease in India responsible for maximum mortality with about 0.3 million deaths per year. The magnitude of cancer problem in the Indian Sub-continent (sheer numbers is increasing due to poor to moderate living standards and inadequate medical facilities. Women are more commonly affected than men. The peak incidence occurs in people in their 60s, but the disease age range is from 29 to 90 years of age and there is great geographic and ethnic variation. Carcinoma gall bladder, a disease of old age, is now found in the younger age group and presents with greater ferocity.

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

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    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.

  1. Pathologic Pattern of Invasive Bladder Carcinoma: Impact of ...

    African Journals Online (AJOL)

    Objective: To describe the pathologic pattern of invasive bladder carcinoma in cystectomy specimens in relation to bilharziasis. Patients and Methods: Between April 2002 and October 2006, 148 consecutive patients with invasive bladder cancer were subjected to radical cystectomy and orthotopic sigmoid bladder ...

  2. Urinary bladder carcinoma with divergent differentiation featuring small cell carcinoma, sarcomatoid carcinoma, and liposarcomatous component.

    Science.gov (United States)

    Yasui, Mariko; Morikawa, Teppei; Nakagawa, Tohru; Miyakawa, Jimpei; Maeda, Daichi; Homma, Yukio; Fukayama, Masashi

    2016-09-01

    Both small cell carcinoma and sarcomatoid carcinoma of the urinary bladder are highly aggressive tumors, and a concurrence of these tumors is extremely rare. We report a case of urinary bladder cancer with small cell carcinoma as a predominant component, accompanied by sarcomatoid carcinoma and conventional urothelial carcinoma (UC). Although the small cell carcinoma component had resolved on receiving chemoradiotherapy, rapid growth of the residual tumor led to a fatal outcome. A 47-year-old man presented with occasional bladder irritation and had a 2-year history of asymptomatic hematuria. Cystoscopy revealed a huge mass in the urinary bladder, and transurethral resection was performed. Microscopically, small cell carcinoma was detected as the major tumor component. Spindle-shaped sarcomatoid cells were also observed that were intermingled with small cell carcinoma and conventional UC. In addition, a sheet-like growth of the lipoblast-like neoplastic cells was observed focally. Initially, by providing chemoradiotherapy, we achieved a marked tumor regression; however, the tumor rapidly regrew after the completion of chemoradiotherapy, and the patient underwent radical cystectomy. Only conventional UC and sarcomatoid carcinoma were identified in the cystectomy specimen. The patient died of the disease 4 months after cystectomy. Urinary bladder cancer may include a combination of multiple aggressive histologies as in the present case. Because the variation in the tumor components may affect the efficacy of therapy, a correct diagnosis of every tumor component is necessary. Copyright © 2016 Elsevier GmbH. All rights reserved.

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

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    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.

  4. 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

  5. Mucoepidermoid carcinoma of lung masquerading as urothelial carcinoma of bladder

    Science.gov (United States)

    Graham, Donna M.; O’Connor, Kate M.; Hinchion, John; Coate, Linda E.; Burke, Louise; Power, Derek G.

    2013-01-01

    Background Mucoepidermoid carcinoma (MEC) of the lung is a rare subtype of non-small cell lung cancer. There is no consensus regarding optimal management for this disease. Case report We present a case of MEC of the lung in a 75 year-old female with a history of superficial urothelial carcinoma of the bladder. The patient was found to have an asymptomatic lung mass. Initial biopsy suggested metastatic recurrence of urothelial carcinoma and therefore, cisplatin and gemcitabine chemotherapy was administered prior to surgical resection. Pathological analysis of the resected specimen confirmed a diagnosis of stage IIIA MEC with focal high-grade features including transitional cell-like areas. Adjuvant radiotherapy was administered due to a positive microscopic resection margin. No chemotherapy was given due to lack of supporting data. The patient developed widespread metastatic disease 3 months following completion of radiotherapy and died 1 month later. Conclusion This case demonstrates the possibility of dual pathology in cases where metastatic disease is suspected. The use of small tissue samples may complicate diagnosis due to the heterogeneity of malignant tumours. PMID:24936321

  6. Adenoma-carcinoma Sequence in the Bladder After Augmentation Cystoplasty

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    Akihiro Naito

    2014-05-01

    Full Text Available We present a case of a 64-year-old woman showing multistep progression from adenoma to adenocarcinoma in the bladder 46 years after augmentation ileocystoplasty. She underwent augmentation ileocystoplasty for tuberculous contracted bladder at 18 years. After 44 years, tubulovillous adenomas were found and resected at the ileovesical anastomosis site. After 2 more years, bladder tumors recurred and revealed adenocarcinomas. Finally, radical cystectomy was required because of frequent recurrence and tumor extensiveness. To our knowledge, this is the first case demonstrating adenoma-carcinoma sequence histopathologically in the bladder after augmentation cystoplasty, indicating multistep carcinogenesis similar to intestinal carcinogenesis.

  7. 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.

  8. Pure Lymphoepithelioma-Like Carcinoma Originating from the Urinary Bladder

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    Takashi Nagai

    2016-03-01

    Full Text Available Lymphoepithelioma-like carcinoma of the urinary bladder (LELCB is a rare variant of infiltrating urothelial carcinoma. We report a case of LELCB in a 43-year-old man. Ultrasonography and cystoscopy revealed two bladder tumors, one on the left side of the trigone and the other on the right side of the trigone. Transurethral resection of the bladder tumors was performed and pathological analysis revealed undifferentiated carcinoma. We therefore performed radical cystectomy and urinary diversion. Immunohistochemically the tumor cells were positive for cytokeratin, but negative for Epstein-Barr virus-encoded small RNA in situ hybridization as found for previous cases of LELCB. The final pathological diagnosis was a lymphoepithelioma-like variant of urothelial carcinoma with perivesical soft tissue invasion. For adjuvant systemic chemotherapy, three courses of cisplatin were administered. The patient subsequently became free of cancer 72 months postoperatively. Based on the literature, pure or predominant LELCB types show favorable prognoses due to their sensitivity to chemotherapy or radiotherapy. An analysis of the apparent diffusion coefficient (ADC values of bladder tumors examined in our institution revealed that the ADC value measured for this LELCB was relatively low compared to conventional urothelial carcinomas. This suggests that measuring the ADC value of a lymphoepithelioma-like carcinoma prior to operation may be helpful in predicting LELCB.

  9. CLINICO-PATHOLOGICAL STUDY OF CARCINOMA GALL BLADDER

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    Ravindra

    2015-12-01

    Full Text Available INTRODUCTION Gall bladder cancer is 5th most common cancer of GIT. It is associated with cholelithiasis in significant number of patients. Cholelithiasis is cause or effect of gall bladder cancer is still uncertain. There are many risk factors which are common to both gall stones and cancer. Preoperative diagnosis of gall bladder cancer is increased with better and new investigation facilities. AIM The study was aimed to assess clinicopathological behaviour, sociodemography, diagnostic modalities and treatment of cancer gall bladder. MATERIAL AND METHODS It was a type of prospective study which included 75 patients with clinical features suggestive of biliary disease. Various diagnostic modalities and treatment options were assessed along with sociodemography and clinical picture. RESULT Common clinical features were pain abdomen, obstructive jaundice and lump. Nearly one third of the patients were having anaemia and abnormal liver function tests. Majority had gall bladder fossa mass with liver extension and gall stones. The most common histopathological variety of carcinoma Gallbladder was Adenocarcinoma. CONCLUSION Carcinoma Gallbladder was found to affect predominantly the older female patients after the age of 40 years. Cholelithiasis was found in 69.3% patients of carcinoma Gallbladder. The most common clinical presentation was pain abdomen (90.7%. The most common histopathological variety of carcinoma Gallbladder was Adenocarcinoma. Majority of patients were treated with palliative measures.

  10. 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.

  11. High expression of HEF1 is associated with poor prognosis in urinary bladder carcinoma

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    Zhang Q

    2014-07-01

    Full Text Available Qi Zhang,1 Hui-Ju Wang,2 Da-Hong Zhang,1 Guo-Qing Ru,3 Xu-Jun He,2 Ying-Yu Ma2 1Department of Urology, 2Key Laboratory of Gastroenterology of Zhejiang Province, 3Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China Abstract: Human enhancer of filamentation 1 (HEF1 is a multidomain scaffolding protein that has been thought to play an important role in the tumor progression of various cancers. HEF1 expression has not previously been reported in urinary bladder carcinoma, and little is known about its prognostic significance. The aim of this study was to evaluate the expression patterns of HEF1 in urinary bladder carcinoma and to investigate its prognostic significance. HEF1 expression was analyzed by immunohistochemistry using tissue microarray. A significant relationship between HEF1 expression and sex, tumor size, number of tumors, invasion depth, lymph node metastasis, and distant metastasis was found, and high expression of HEF1 was associated with worse overall survival when compared to low expression of HEF1. Multivariate analysis showed that HEF1 expression was an independent prognostic factor for overall survival in urinary bladder carcinoma. We investigated HEF1 expression in urinary bladder carcinoma and found that high HEF1 expression was associated with advanced stage, large tumor size, and shortened progression-free survival. Although the biologic function of HEF1 in urinary bladder carcinoma remains unknown, the expression of HEF1 can provide new prognostic information for disease progression. Keywords: human enhancer of filamentation 1, progression-free survival, immunohistochemistry, metastasis, bladder cancer

  12. 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.

  13. Pure primary small cell carcinoma of urinary bladder: A rare diagnostic entity

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    Sonia Gon

    2013-01-01

    Full Text Available Small cell carcinoma of the bladder is a rare, aggressive, poorly differentiated neuroendocrine neoplasm accounting for only 0.3-0.7% of all bladder tumors. Since the tumor is very rare, pathogenesis is uncertain. Small cell carcinomas of the urinary bladder are mixed with classic urothelial carcinomas or adenocarcinomas of the bladder in 68% cases, making pure primary small cell carcinoma even a rarer entity. The unknown etiology and natural history of small cell carcinoma of the urinary bladder represent a challenge both to the pathologist and urologists for its diagnosis and treatment, respectively.

  14. Isolated Meningeal Recurrence of Transitional Cell Carcinoma of the Bladder

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    Catherine Butchart

    2010-06-01

    Full Text Available Meningeal carcinomatosis occurs in 1–18% of patients with solid tumours, most commonly carcinomas of the breast and lung or melanomas. There are relatively few reports of meningeal carcinomatosis in transitional cell carcinoma of the bladder. Isolated meningeal recurrence is particularly uncommon, and we present an unusual case of this in a 58-year-old man. The case was further complicated by the somewhat atypical presentation with a confirmed ischaemic stroke. The patient died one month after presentation.

  15. Angiogenesis in urinary bladder carcinoma as defined by ...

    African Journals Online (AJOL)

    Background: Among the patients with bladder cancer, a group is still at risk of disease recurrence, progression, and death from their cancer after curative treatment. Angiogenesis is a crucial pathogenic mechanism for this type of urothelial carcinoma and is a potential therapeutic target. Objectives: To quantify tumor ...

  16. Carcinoma of Urinary Bladder in a Region of Low Schistosomiasis ...

    African Journals Online (AJOL)

    Aim: To study the geographical pathology of carcinoma of the urinary bladder as regards both its association with endemic schistosomiasis and the variable proportions of its histological types. Methods: A 30-year retrospective analysis was carried out with regard to Igbo patients who inhabit a region of low incidence of ...

  17. [Glandular squamous cell carcinoma of the urinary bladder].

    Science.gov (United States)

    Kovylina, M V; Pushkar', D Iu; Zaĭrat'iants, O V; Rasner, P I

    2006-01-01

    The paper gives a clinical observation of a 52 year-old male with a rare histological urinary bladder tumor primary grandular-squamous-cell carcinoma (pT3N IM0). The tumor is represented by two components large acinic-cell adenocarcinoma and squamous-cell carcinoma with keratinization, which smoothly pass one into another; the tumor has grown through all layers of the urinary bladder wall but it has failed to grow into the peritoneum. A microscopic study has indicated that the urachus is intact. Metastases were found in 3 of 8 lymph nodes: one showed high-grade adenocarcinoma and two others displayed average-grade squamous-cell carcinoma.

  18. Computed tomography in staging of bladder carcinoma (Prospective study)

    International Nuclear Information System (INIS)

    Lee, Kyung Soo; Choi, Byung Ihn; Han, Man Chung

    1985-01-01

    Staging of carcinoma of the urinary bladder is important for the choice of therapy and also has prognostic implications. Hitherto the staging has been based upon cystoscopy with biopsy, transurethral resection, and palpation with complementary radiographic examinations such as cystography, urography, lymphangiography, ultrasound and angiography. However, with all these methods, the staging of bladder carcinomas still uncertain and inferior to CT. Authors analyzed CT staging of bladder cancers and compared with pathologic staging of laparotomy results. The results are as following: 1. Overall accuracy of CT staging in bladder carcinoma was 72 percent. 2. Overstaging was 20 percent (5/25) and understaging was 8 percent (2/25). 3. All of CT stage B cancers were proven to be stage B, pathologically. 4. In 6 cases of CT static cancers, only one was correct, 3 were overstaged and 2 were understaged. 5. In 7 cases of CT stage D cancers, 5 were correct and 2 were overstaged. 6. CT detected only 2 cases of pelvic lymph node involvement in 4 of pathologically proven lymphadenopathy

  19. Radionuclide targeting with particular emphasis on urinary bladder carcinoma

    International Nuclear Information System (INIS)

    Sjoestroem, A.

    2001-01-01

    The incidence of urinary bladder carcinoma is increasing and many patients die every year of this disease despite assumed radical therapy. Thus, there is a need for improved methods of diagnosis and therapy. Radionuclide targeting is based on achieving specific delivery of radioactive nuclides to tumour cells with minimal damage to surrounding normal tissues. Two possible target structures are the epidermal growth factor (EGF) receptor and the related receptor HER-2. Cellular binding and retention of 125 I-EGF-dextran conjugates was investigated in two bladder carcinoma cell lines. The conjugate bound specifically to the EGF receptor with delayed maximum binding, limited intracellular degradation and prolonged cellular retention compared to 125 I-EGF. EGF was labelled using different radionuclides and methods. All the labelled variants bound specifically to the tumour cells although the cellular binding patterns and retention varied considerably. 111 In-DTPA-EGF had highest cellular retention and in decreasing order 211 At-benzoyl-EGF and 125 I-labelled EGF. Bladder cancer spheroids bound both 125 I-EGF-dextran as well as 125 I-EGF. Conjugate binding increased during a 48 h incubation period and was most prominent in the outer cell layers. The length of the dextran chain appeared not to alter the binding pattern. The expression of EGF receptors and HER-2 in metastases and primary bladder carcinoma tumours was investigated. Both receptors were expressed in the majority of metastases and primary tumours. Targeting the EGF receptor and/or HER-2 in urinary bladder carcinoma is an exciting new concept

  20. PDT-induced apoptosis in bladder carcinoma cells

    Science.gov (United States)

    Bachor, Ruediger; Reich, Ella D.; Kleinschmidt, Klaus; Repassy, Denes; Hautmann, Richard E.

    1999-02-01

    Photodynamic therapy (PDT) is a highly efficient inducer of apoptosis in EY-28 bladder carcinoma cells, resulting in extensive DNA fragmentation. Bladder carcinoma cells EY-28 (Tumorbank Heidelberg, Germany) were incubated for 1 h with 1 (mu) g AamTPPn/ml or 2 (mu) g AamTPPn/ml. After incubation cells were refed with complete medium and irradiated with 0.75 J/cm2. To identify apoptotic cells, a in situ cell death detection kit POD (Boehringer Mannheim, Germany) was used. The chromatin condensation characteristic to apoptotic cells was detected by transmission electron microscopy. Using 1 (mu) g AamTPPn/ml and 2 (mu) g AamTPPn/ml (9-Acetamido-2,7,12,17- tetra-n-Porpylporphycene), respectively, and irradiation at 0.75 J/cm2, a percentage of 36.9% and 54.7%, respectively, of apoptotic cells was detected.

  1. [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.

  2. Bladder hemorrhage after radiotherapy for carcinoma of the cervix uteri

    International Nuclear Information System (INIS)

    Matsuyama, Toshitake; Tsukamoto, Naoki; Sugimori, Hajime; Yoshino, Teruo; Kashiwamura, Masamichi.

    1979-01-01

    The relationship among the incidence, the time of occurrence, and radiation dose was studied in regard to hemorrhagic cystitis after radiotherapy for carcinoma of the cervix uteri. Of 1004 patients with carcinoma of the cervix uteri observed between 1961 and 1974, 28 (2.8%) had bladder hemorrhage seemingly due to radiation injury (0.7% were serious). Incidences varied every year. The radiation dose was increased from 4000 to 6000 rad after 1971. In addition to this external dose, because the depth-dose has also increased, the rate of bladder hemorrhage has become high. Seven patients with serious bladder hemorrhage were exposed to more than 5000 rad of 60 Co. Bladder hemorrhage occurred comparatively frequently in patients in whom two hila were irradiated. It usually occurred a few years after irradiation (about 1 year after initial rectal hemorrhage). It continued for approximately 1 year in 21 patients, for approximately 3 years in 4 patients, and for approximately 4 years in 3 patients. Adrenochrome (a hemostatic agent) and antiplasmin were used as therapeutic agents. Serious patients improved remarkably when a large amount of diluted formaline solution or conjugated estrogen was administered intravenously. (Namekawa, K.)

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

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    Ismaili Nabil

    2011-11-01

    Full Text Available Abstract Small cell carcinoma of the bladder (SCCB is rare, highly aggressive and diagnosed mainly at advanced stages. Hematuria is the main symptom of this malignancy. The origin of the disease is unknown; however the multipotent stem cell theory applies best to this case. Histology and immunohistochemistry shows a tumour which is indistinguishable from small cell lung carcinoma (SCLC. Coexistence of SCCB with other types of carcinoma is common. The staging system used is the TNM-staging of bladder transitional cell carcinoma. The treatment is extrapolated from that of SCLC. However, many patients with SCCB undergo radical resection which is rarely performed in SCLC. Patients with surgically resectable disease ( or = cT4bN+M+ should be managed with palliative chemotherapy based on neuroendocrine type regimens comprising a platinum drug (cisplatin in fit patients. The prognosis of the disease is poor mainly in the case of pure small cell carcinoma. Other research programs are needed to improve the outcome of SCCB.

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

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    Yi-Ping Huang

    2013-01-01

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

  5. Carcinoma transverse colon masquerading as carcinoma gall bladder.

    Science.gov (United States)

    Munghate, Anand; Kumar, Ashwani; Singh, Harnam; Singh, Gurpreet; Singh, Bimaljot; Chauhan, Mahak

    2014-04-01

    Colorectal cancer is one of the most common cancer worldwide .Its incidence is reported to be increasing in developing countries. It commonly presents with weight loss, anaemia, lump abdomen, change of bowel habit, obstruction or fresh rectal bleeding. Beside these common modes of presentations, there are some rare manifestations which masqueraded as different disease like obstructive jaundice, empyema gall bladder or cholecystitis. A 60-year-old male presented to hospital with right sided pain abdomen. On abdominal examination mild tenderness was present in right hypochondrium. Intra operatively gall bladder was separated from the adjoining gut, peritoneum and liver bed and was removed. On further exploration, there was a large mass in the vicinity of the gall bladder related to transverse colon. Extended right hemicolectomy was done. Histopathological examination of gut mass revealed adenocarcinoma of transverse colon with free margins and gall bladder showed cholecystitis with no evidence of malignancy. We present an interesting case of colon cancer colon that caused diagnostic confusion by mimicking as cholecystitis. Colorectal cancer constitutes a major public health issue globally. Therefore, public awareness, screening of high-risk populations, early diagnosis and effective treatment and follow-up will help to reduce its occurance and further complications.

  6. Gall bladder carcinoma with ampullary carcinoma: A rare case of double malignancy

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    Praveer Rai

    2013-01-01

    Full Text Available Simultaneous double cancers in the biliary system are rare. Most are associated with pancreaticobiliary maljunction (PBM. However, it can occur in patients without PBM. Differentiation between these events is important since these two mechanistic origins imply different stages of disease, as well as different subsequent treatments and prognoses. Herein, we report a case of ampullary carcinoma associated with gall bladder carcinoma diagnosed nonoperatively and palliated with biliary metal stenting.

  7. Urothelial Carcinoma of the Urinary Bladder in Young Adults — Clinical Experience at Taipei Veterans General Hospital

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    Yu-Ching Wen

    2005-06-01

    Conclusion: Urothelial carcinoma of the urinary bladder in young adults is usually associated with low grade and low stage. Invasive bladder cancer had no worse a survival rate than superficial bladder cancer.

  8. Clear cell urothelial carcinoma of the urinary bladder: a case report and review of the literature.

    Science.gov (United States)

    Knez, Virginia M; Barrow, Willis; Lucia, M Scott; Wilson, Shandra; La Rosa, Francisco G

    2014-08-14

    The occurrence of clear cell tumors in the bladder is not uncommon. Clear cell dysplasia is well-described and characterized by focal replacement of transitional mucosa by cells with abundant clear cytoplasm, nuclear enlargement, and a granular chromatin pattern. Clear cells can also be seen in clear cell adenocarcinoma, which is rare, comprising 0.5% to 2.0% of the reported bladder carcinomas. Other clear cell tumors found in the bladder to be considered in the differential diagnosis are tumors of Müllerian origin and metastatic lesions, such as renal cell carcinoma, clear cell sarcoma, and malignant melanoma. Clear cell urothelial carcinoma is exceedingly rare, with only nine clinical cases described in the literature. We report the case of a 75-year-old Caucasian man who presented with intermittent hematuria, in whom a bladder tumor was identified. A final histopathology examination of a cystoprostatectomy specimen revealed a pT3b, G3 urothelial carcinoma of clear cell type (>90% clear cells) and a prostatic adenocarcinoma of Gleason grade 3+3 (score=6). The bladder tumor consisted of sheets of malignant cells with severe nuclear atypia and abundant clear cytoplasm; no glandular or tubular structures were identified. Tumor cells were periodic acid-Schiff positive and negative after diastase treatment; additional mucicarmine and oil red O stains were negative. Immunohistochemical stains showed the tumor cells positive for cytokeratin 7 (CK7), p63 (>80% nuclei), p53 (about 30% nuclei), vimentin, E-cadherin, cluster of differentiation (CD10), and Ki-67 (>70% nuclei). Stains for cell adhesion molecule 5.2 (CAM 5.2), CD117, cytokeratin 20 (CK20), human melanoma black 45 (HMB-45), paired box protein (PAX 8), placental alkaline phosphatase (PLAP), prostate specific antigen (PSA), renal cell carcinoma (RCC), cancer antigen 25 (CA25), leukocyte common antigen (LC), S-100 protein, and uroplakin III were all negative. The tumor marker profile was consistent with clear

  9. Urothelial carcinoma arising within bladder diverticulum—Report of a case and review of the literature

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    Hung-En Chen

    2016-09-01

    Full Text Available Bladder diverticulum is an outpouching of bladder mucosa through the musculature of the bladder wall. The incidence of bladder diverticulum in Taiwan is about 1.7% in children and 23.4% in adults. Intradiverticular carcinoma of urinary bladder is uncommon. It ranges from 0.8% to 14.3%. Here we report a case of urothelial carcinoma within a bladder diverticulum. A 60-year-old male patient had history of BPH under medical treatment and right ureteral stone treated with extracorporeal shock wave lithotripsy (ESWL. He presented with painless gross hematuria about 3 months after ESWL. Intravenous pyelography showed a filling defect within the bladder diverticulum. Histopathological diagnosis of low grade urothelial carcinoma arising from the bladder diverticulum was made following cystoscopic biopsy. Laparoscopic partial cystectomy was performed with subsequent intravesical chemotherapy. Tumor recurrence was found not from the previous diverticulum but from another area during regular cystoscopy at the 6-month postoperative follow up. He underwent transurethral resection of bladder tumor. Pathology revealed a noninvasive, high grade urothelial carcinoma. There was no further bladder tumor recurrence during the 1-year follow-up period. Bladder-sparing surgery with close cystoscopy follow up for intradiverticular urothelial carcinoma can be applied as an alternative treatment modality.

  10. 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.

  11. Vinorelbine rescue therapy for dogs with primary urinary bladder carcinoma.

    Science.gov (United States)

    Kaye, M E; Thamm, D H; Weishaar, K; Lawrence, J A

    2015-12-01

    The goal of this study was to evaluate the anti-tumour activity and toxicoses of vinorelbine as a palliative rescue therapy for dogs with primary urinary bladder carcinoma. Thirteen dogs refractory to prior chemotherapeutics and one dog naïve to chemotherapeutic treatment were enrolled. Vinorelbine (15 mg m(-2) IV) was administered intravenously along with concurrent oral anti-inflammatory drugs, if tolerated. A median of six doses of vinorelbine (range: 1-16) was administered. Two dogs (14%) had partial responses, and eight (57%) experienced stable disease. Subjective improvement in clinical signs was noted in 11 dogs (78%). Adverse events were mild and primarily haematological in nature. Median time to progression was 93 days (range: 20-239 days). Median survival time for all dogs was 187 days; median survival for 13 pre-treated dogs was 207 days. Vinorelbine may have utility in the management of canine primary urinary bladder carcinoma and should be evaluated in a prospective study. © 2013 John Wiley & Sons Ltd.

  12. Preoperative radiation therapy for muscle-invading bladder carcinoma

    International Nuclear Information System (INIS)

    Cox, J.A.; Greven, K.M.; Anscher, M.S.; Morgan, T.M.; Scott, J.

    1991-01-01

    This paper reports on low-dose and high-dose radiation therapy (RT) followed by cystectomy for bladder carcinoma that was evaluated for survival, failure patterns, and complications as these outcomes have been incompletely documented in the past. One hundred five patients with clinical stages T2-T4 (muscle-invading) transitional cell carcinoma of the bladder who completed preoperative RT followed by total cystectomy were evaluated. Eighty-five patients received 20-27 Gy in 4-7 fractions (group A). Twenty patients received 40-50 Gy in 20-28 fractions (group B). Actuarial 5-year survival was 45% and 29% (P = .06) for groups A and B, respectively; 6% of group A was stage T4 compared with 30% of group B. Five-year actuarial survival for patients with stages T2-T3 in groups A and B was 46% and 42%, respectively, while that for T4 was 33% and 0% in groups A and B, respectively. Multivariate analysis revealed that stage, grade, and presence of hydronephrosis independently affected survival. Five-year actuarial local control rates for T2, T3, and T4 were 93%, 93%, and 22%, respectively, with no significant difference between RT groups. Rates of distant metastasis and complications versus preoperative regime and stage were similar

  13. OPIUM USE IN TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER

    Directory of Open Access Journals (Sweden)

    A. Nourbakhsh

    2006-08-01

    Full Text Available Opium use is one of the most common forms of substance abuse in Iran and there are some evidence indicating it is a risk factor of transitional cell carcinoma (TCC of the urinary bladder. The majority of opium users are also cigarette smokers, so consideration of the high prevalence of smoking which is the most important risk factor of TCC of the urinary bladder among opium users is essential to assess the role of opium use as a possible risk factor of TCC. This study was done to evaluate the role of opium as a risk factor of TCC. A case-control study was performed on 255 individuals diagnosed with TCC of the urinary bladder by pathologic light microscopic examination of the tumor biopsies. Control population was chosen from individuals who had no history or presenting signs or symptoms of urinary problems. Case and control groups were matched by sex and age and also by cigarette smoking habits. Forty-one (18.1% of the cases and 12 (5% of controls were recognized to be opium users. Mantel-Haenszel analysis showed an odds ratio of 3.88, with 95% confidence interval of 1.99-7.57 and P value of < 0.001. Results indicate that opium use is a risk factor for TCC. The majority of opium users are also cigarette smokers, which is another important risk factor for TCC. Routine urine cytology and early evaluation in the patients presenting with any of the symptoms of urinary bladder malignancy by means of cystoscopy and urine cytology are highly recommended.

  14. Urine and bladder washing cytology for detection of urothelial carcinoma: standard test with new possibilities

    International Nuclear Information System (INIS)

    Flezar, Margareta Strojan

    2010-01-01

    Light microscopic evaluation of cell morphology in preparations from urine or bladder washing containing exfoliated cells is a standard and primary method for the detection of bladder cancer and also malignancy from other parts of the urinary tract. The cytopathologic examination is a valuable method to detect an early recurrence of malignancy or new primary carcinoma during the follow-up of patients after the treatment of bladder cancer. Characteristic cellular and nuclear signs of malignancy indicate invasive or in situ urothelial carcinoma or high-grade papillary urothelial carcinoma. However, low sensitivity of the method reflects the unreliable cytopathologic diagnosis of low-grade urothelial neoplasms as cellular and nuclear signs of malignancy in these neoplasms are poorly manifested. Many different markers were developed to improve the diagnosis of bladder carcinoma on urinary samples. UroVysion™ test is among the newest and most promising tests. By the method of in situ hybridization one can detect specific cytogenetic changes of urothelial carcinoma

  15. Surgical management of bladder transitional cell carcinoma in a vesicular diverticulum: case report.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2011-08-01

    We report a case of primary transitional cell carcinoma (TCC) of a bladder diverticum along with a literature review. A 55-year-old male presented with painless gross hematuria. A histological diagnosis of TCC within a bladder diverticulum was made following cystoscopical examination. Initially transurethral resection of bladder tumour with subsequent intravesical chemotherapy followed. As a result of recurrence and in view of bladder-sparing therapy, a distal partial cystectomy was performed. This report demonstrates that conservative bladder-sparing treatment can be achieved and subsequently followed by vigilant cystoscopy.

  16. Surgical management of bladder transitional cell carcinoma in a vesicular diverticulum: case report.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2012-02-01

    We report a case of primary transitional cell carcinoma (TCC) of a bladder diverticum along with a literature review. A 55-year-old male presented with painless gross hematuria. A histological diagnosis of TCC within a bladder diverticulum was made following cystoscopical examination. Initially transurethral resection of bladder tumour with subsequent intravesical chemotherapy followed. As a result of recurrence and in view of bladder-sparing therapy, a distal partial cystectomy was performed. This report demonstrates that conservative bladder-sparing treatment can be achieved and subsequently followed by vigilant cystoscopy.

  17. Transitional cell carcinoma of the bladder in childhood: radiological findings and differential diagnosis

    International Nuclear Information System (INIS)

    Casado, L.; Mansilla, F.; Mansilla, M.D.; Marin, A.

    1998-01-01

    We present a case of transitional cell carcinoma of the bladder in an 11-year-old boy. The rarity of these tumors during childhood is pointed out. The radiological and ultrasonographic findings are described and the differential diagnosis is discussed with respect to other bladder tumors occurring in childhood. (Author) 11 refs

  18. CT in the diagnosis of squamous cell carcinoma of urinary bladder

    International Nuclear Information System (INIS)

    Narumi, Yoshifumi; Mitani, Takashi; Kuriyama, Keiko

    1988-01-01

    CT findings of 8 operated cases with squamous cell carcinoma of urinary bladder were reviewed. All of them had advanced stage tumor with invasion into perivesical fat or organs (≥ T3b), and with or without lymphnode involvement. We compared them with 15 operated cases with advavced transitional cell carcinoma of urinary bladder (≥ T3b) especially in regard to the direction of tumor growth, and the frequency of invasion into perivesical organs and lymphnode involvement. Futhermore, we studied a relation between CT findings and histopathological stages of the squamous cell carcinoma of urinary bladder. Squamous cell carcinoma of urinary bladder showed predominant extravesical growth as the stage advanced, while transitional cell carcinoma generally showed predominant intravesical growth. Squamous cell carcinoma invaded into perivesical organs and metastasized to lymphnodes more frequently than transitional cell carcinoma of control group. Accuracy of CT staging of squamous cell carcinoma of urinary bladder was found to be 100 % in T stage and 75 % in N stage. (author)

  19. Urothelial carcinoma of urinary bladder with exclusive heterologous component of epithelioid rhabdomyosarcoma at metastatic site.

    Science.gov (United States)

    Agarwal, Poojan; Pasricha, Sunil; Gupta, Gurudutt; Sharma, Anila; Mehta, Anurag

    2018-01-01

    Urothelial carcinoma of urinary bladder with divergent differentiation into rhabdomyosarcoma (RMS) is an extremely uncommon aggressive phenomenon. We present a case of a 74-year-old male with bladder carcinoma which metastasized to the abdominal wall as epithelioid RMS. To the best knowledge of our literature searches, an oligometastasis of exclusive heterologous component has not been described before. The clinical, radiological, and immunohistochemistry profile of the patient supported the monoclonal nature of the tumor.

  20. Metastatic Gastric Linitis Plastica from Bladder Cancer Mimicking a Primary Gastric Carcinoma: a Case Report

    International Nuclear Information System (INIS)

    Hong, Won Sun; Chung, Dong Jin; Lee, Jae Mun; Byun, Jae Ho; Hahn, Seong Tae

    2009-01-01

    Primary gastric carcinoma is the most common cause of linitis plastica. Less frequently, metastatic gastric cancer from the breast, omental metastases and non-Hodgkin lymphoma involving the stomach have been reported to show similar radiographic findings as for linitis plastica. A metastatic gastric cancer from bladder cancer is extremely rare. We present an unusual case, the first to our knowledge, of gastric linitis plastica that resulted from a metastatic urothelial carcinoma of the bladder

  1. Factors related to recurrence of bladder transitional cell carcinoma after transurethral resection of bladder tumor (TUR-BT)

    International Nuclear Information System (INIS)

    Nam, Ki Dong; Koo, Bong Sik; Yoon, Seong Kuk; Park, Byung Ho; Nam, Kyung Jin; Choi, Jong Cheol; Lee, Ki Nam; Lee, Young Il; Chung, Duck Hwan

    1998-01-01

    The purpose of this study is to evaluate factors related to the recurrence of TCC (transitional cell carcinoma) in the urinary bladder after transurethal resection of bladder tumor (TUR-BT). We retrospectively reviewed 54 patients in whom TCC (transitional cell carcinoma) after TUR-BT had been confirmed. Recurrence was evaluated by US, CT, cystoscopy and urine smear during the follow-up period of 6 months. The multiplicity, shape, size, and calcification of TCC, as revealed by radiologic studies, were evaluated retrospectively before TUR-BT. After TUR-BT, the histologic grade and pathologic stage of TCC were evaluated. Radiologically, multiple and/or sessile type TCC had a higher recurrence rate than the single and/or pedunculated type. Pathologically, when the grade and stage of bladder tumor were higher, recurrent rates were higher. (author). 17 refs., 3 tabs., 3 figs

  2. 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.

  3. Expression and Role of GPR87 in Urothelial Carcinoma of the Bladder

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    Yoshiyuki Kakehi

    2013-06-01

    Full Text Available The orphan GPR87 has recently been matched with its ligand LPA, which is a lipid mediator with multiple physiological functions, including cancer cell proliferation. This study aimed to clarify the role of GPR87 in urothelial carcinoma of the bladder. GPR87 expression was assessed in seven human bladder cancer cell lines. A replication-deficient recombinant adenoviral vector expressing shRNA targeting GPR87 (Ad-shGPR87, was constructed. Gene silencing was carried out using Ad-shGPR87. Immunohistochemical analysis was performed for transurethral resection of bladder tumor samples from 71 patients with non-muscle-invasive bladder cancer. We observed GPR87 expression in five of the seven cell lines, and silencing GPR87 gene expression significantly reduced cell viability. GPR87 expression was positive in 38 (54% of 71 tumors. Ki-67 index was associated with positive GPR87 staining status (p < 0.0001. Patients with GPR87-positive tumors had shorter intravesical recurrence-free survival than those with GPR87-negative tumors (p = 0.010. Multivariate analysis revealed that GPR87 staining status was an independent prognostic parameter for intravesical recurrence (p = 0.041. Progression from non-muscle-invasive to muscle-invasive tumor was more frequently observed in patients with GPR87-positive tumors, although this trend did not reach statistical significance (p = 0.056. These results warrant further prospective studies to clarify the role of GPR87 expression in intravesical recurrence and progression in bladder cancer.

  4. Primary Signet-Ring Carcinoma in the Bladder Presenting as a Hypervascular Luminal Polypoid Mass

    International Nuclear Information System (INIS)

    Jeong, Min Sun; Choi, Seung A; Jung, Yoon Young; Cho, Young Kwon; Lee, Won Mi; Lee, Seung Wook

    2012-01-01

    Primary signet-ring carcinoma is a very aggressive and rare variant of a primary urinary bladder cancer, accounting for less than 1% of cases. We reported on a 76-year-old patient with primary signet-ring carcinoma who occurred metastatic lymphadenopathy with extranodal invasion causing intraluminal tumor thrombi in the adjacent vein, and pulmonary metastasis over the course of three months. We demonstrated the computed tomography findings of primary signet-ring carcinoma of the bladder and correlated the imaging findings with the pathologic features. We reviewed the distinguishing imaging findings of the primary signet-ring carcinoma compared with urothelial cell carcinoma, the most common subtype of the bladder cancer.

  5. 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...

  6. Response and toxicity of photodynamic therapy for canine bladder carcinoma

    International Nuclear Information System (INIS)

    Beck, E.R.; Dunstan, R.W.

    1992-01-01

    This investigation was to determine PDT efficacy and tolerance (both short term and long term) in dogs with spontaneously occurring transitional cell carcinoma of the urinary bladder. All patients were T2-T3, N x , M o . 27 dogs were given Photofrin II at 3.0 mg/kg IV, and 72 hours later doses of 632 nm light from 5-25 J/cm 2 . In 25/27 dogs, PDT resulted in complete remission of stranguria, hematuria and pollackiuria within one week of treatment. Gross hematuria increased in 7 dogs for the first 2 days following treatment, but then disappeared completely. Duration of clinical remission varied from 5-25 weeks after single treatment, within a median duration of 10 weeks. Doses of light from 5-10 J/cm 2 were well tolerated, with only mild toxicity for 1-3 days. Moderate toxicity showed in some dogs given 10-15 J/cm 2 . In all dogs given 25 J/cm 2 and 46% of those given 15 J/cm 2 , severe abdominal cramping, fecal incontinence, perforations and sepsis was seen. A second PDT treatment of 10-15 J/cm 2 following recurrence of clinical signs was administered to 9 dogs, without an increase in toxicity beyond that seen following the first treatment. Median duration of this second remission was 8 weeks, with a range of 5-12 weeks. 4-5 multiple PDT treatments were given to 4 dogs without any clinical symptoms of decreased bladder function. Each treatment produced an additional remission of variable length. (author). 14 refs., 1 fig., 1 tab

  7. Calcitonin-producing well-differentiated neuroendocrine carcinoma (carcinoid tumor of the urinary bladder: case report

    Directory of Open Access Journals (Sweden)

    De Rosa Gaetano

    2005-07-01

    Full Text Available Abstract Background The occurrence of calcitonin-secreting primary carcinoid tumor of the urinary bladder is extremely rare. Case presentation The case of a 68-year-old male with carcinoid tumor arising in the urinary bladder is presented. Transurethral resection of a polypoid small tumor 0.4 cm in diameter was performed. Immunohistochemical study using neuroendocrine markers allowed a straightforward diagnosis of a low-grade neuroendocrine carcinoma (carcinoid tumor of the urinary bladder. Immunohistochemistry demonstrated calcitonin immunoreactivity in the most of the tumor cells. Conclusion This tumor shows specific clinical, macroscopical and histological features and must be considered in the differential diagnosis of bladder neoplasms.

  8. Prognostic significance of epidermal growth factor receptor (EGFR) over expression in urothelial carcinoma of urinary bladder.

    Science.gov (United States)

    Hashmi, Atif Ali; Hussain, Zubaida Fida; Irfan, Muhammad; Khan, Erum Yousuf; Faridi, Naveen; Naqvi, Hanna; Khan, Amir; Edhi, Muhammad Muzzammil

    2018-06-07

    Epidermal growth factor receptor (EGFR) has been shown to have abnormal expression in many human cancers and is considered as a marker of poor prognosis. Frequency of over expression in bladder cancer has not been studied in our population; therefore we aimed to evaluate the frequency and prognostic significance of EGFR immunohistochemical expression in locoregional population. We performed EGFR immunohistochemistry on 126 cases of bladder cancer and association of EGFR expression with tumor grade, lamina propria invasion, deep muscle invasion and recurrence of disease was evaluated. High EGFR expression was noted in 26.2% (33 cases), 15.1% (19 cases) and 58.7% (74 cases) revealed low and no EGFR expression respectively. Significant association of EGFR expression was noted with tumor grade, lamina propria invasion, deep muscle invasion and recurrence status while no significant association was seen with age, gender and overall survival. Kaplan- Meier curves revealed significant association of EGFR expression with recurrence while no significant association was seen with overall survival. Significant association of EGFR overexpression with tumor grade, muscularis propria invasion and recurrence signifies its prognostic value; therefore EGFR can be used as a prognostic biomarker in Urothelial bladder carcinoma.

  9. Human bladder cancer diagnosis using multiphoton microscopy

    Science.gov (United States)

    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.

  10. Sarcomatoid carcinoma associated with small cell carcinoma of the urinary bladder: a series of 28 cases.

    Science.gov (United States)

    Urrea, Yuly Ramirez; Epstein, Jonathan I

    2017-09-01

    The association of sarcomatoid carcinoma (SC) with small cell carcinoma (SCC) has not been systematically studied. We identified 39 consult cases between 2001 and 2016 with available slides for review in 28 cases. There were 19 men and 9 women (mean age: 78 years [51-89]). In 26 (92.8%) cases, the sarcomatoid component had nonspecific malignant spindle cells, 4 (14%) chondrosarcoma, 2 (7%) myxoid sarcomatous, 1 (3.5%) osteosarcoma, and 1 (3.5%) rhabdomyosarcoma. The predominant component was SCC in 11 (39%) cases, urothelial carcinoma in 6 (21%), sarcomatoid in 3 (10%), and equal sarcomatoid and SCC in 8 (29%). There were 3 morphological groups: group 1 (18/28 [64%]) showed a gradual transition from SCC to other components; group 2 (5/28 [18%]) had an abrupt transition from SCC to other components; and in group 3 (5/28 [18%]), the SCC was separate from other components. In group 1, 12 (66%) cases of SCC showed a gradual transition to sarcomatoid areas; 3 (17%) to urothelial carcinoma; and 3 (17%) to multiple components including squamous cell carcinoma, urothelial carcinoma, and sarcomatoid. Mortality did not differ based on pathological groups. The 36-month actuarial risk of death was 64.3%. The multitude of different components in these tumors is further evidence of the remarkable ability of carcinoma of the bladder to show divergent differentiation with, in some cases, gradual transition between SCC and other elements including sarcomatoid. Greater recognition of this entity with chemotherapy targeted to the various histological elements may have important therapeutic implications. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Expression profiles of variation integration genes in bladder urothelial carcinoma.

    Science.gov (United States)

    Wang, J M; Wang, Y Q; Gao, Z L; Wu, J T; Shi, B K; Yu, C C

    2014-04-30

    Bladder cancer is a common cancer worldwide and its incidence continues to increase. There are approximately 261,000 cases of bladder cancer resulting in 115,000 deaths annually. This study aimed to integrate bladder cancer genome copy number variation information and bladder cancer gene transcription level expression data to construct a causal-target module network of the range of bladder cancer-related genomes. Here, we explored the control mechanism underlying bladder cancer phenotype expression regulation by the major bladder cancer genes. We selected 22 modules as the initial module network to expand the search to screen more networks. After bootstrapping 100 times, we obtained 16 key regulators. These 16 key candidate regulatory genes were further expanded to identify the expression changes of 11,676 genes in 275 modules, which may all have the same regulation. In conclusion, a series of modules associated with the terms 'cancer' or 'bladder' were considered to constitute a potential network.

  12. Primary enteric-type adenocarcinomas of the urinary bladder are histogenetically analogous to colorectal carcinomas: Immunohistochemical evaluation of 109 cases

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    Saad S. Eissa

    2010-04-01

    In conclusion, primary non-urachal enteric-type adenocarcinoma of the urinary bladder is morphologically and immunophenotypically similar – if not identical – to colonic adenocarcinoma. The frequent association of enteric carcinomas of the urinary bladder with intestinal metaplasia and/or colonic-type adenomas with dysplasia suggests possible carcinogenetic pathways similar to that observed in colorectal carcinomas.

  13. Analysis of failure following definitive radiotherapy for invasive transitional cell carcinoma of the bladder

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    Mameghan, Hedy; Fisher, Richard; Mameghan, Jill; Brook, Susan

    1995-01-15

    Purpose: To assess prognostic factors for bladder relapse and distant failure following definitive radiotherapy for invasive transitional cell carcinoma (TCC) of the bladder. Methods and Materials: Retrospective review of patients treated in the period 1977 to 1990 by definitive radiotherapy. The factors studied included age, sex, T stage, histological grade, tumor multiplicity, ureteric obstruction, total radiation dose, and use of neoadjuvant chemotherapy. The endpoints studied were bladder relapse and distant failure. Results: There were 342 patients with a mean follow-up time of 7.9 years. Bladder relapse was observed in 159 patients. The overall actuarial bladder relapse rate at 5 years was 55% (SE = 3%). Prognostic factors for a higher bladder relapse rate were: tumor multiplicity (p < 0.001), presence of ureteric obstruction (p = 0.001), and higher T stage (p 0.044). Distant failure occurred in 39 patients. The overall actuarial distant failure rate at 5 years was 28% (SE = 3%). Prognostic factors for a higher distant failure rate were: ureteric obstruction (p = 0.003) and higher T stage (p = 0.030). Conclusion: In our study, patients with invasive bladder TCC fell into distinct prognostic groups determined by the three independent factors, ureteric obstruction, tumor multiplicity, and T stage. These factors provided estimated risks of bladder relapse by 5 years which ranged from 34% to 91%. Knowledge of these prognostic factors can help in the selection of patients more suited for bladder preservation by definitive radiotherapy.

  14. Analysis of failure following definitive radiotherapy for invasive transitional cell carcinoma of the bladder

    International Nuclear Information System (INIS)

    Mameghan, Hedy; Fisher, Richard; Mameghan, Jill; Brook, Susan

    1995-01-01

    Purpose: To assess prognostic factors for bladder relapse and distant failure following definitive radiotherapy for invasive transitional cell carcinoma (TCC) of the bladder. Methods and Materials: Retrospective review of patients treated in the period 1977 to 1990 by definitive radiotherapy. The factors studied included age, sex, T stage, histological grade, tumor multiplicity, ureteric obstruction, total radiation dose, and use of neoadjuvant chemotherapy. The endpoints studied were bladder relapse and distant failure. Results: There were 342 patients with a mean follow-up time of 7.9 years. Bladder relapse was observed in 159 patients. The overall actuarial bladder relapse rate at 5 years was 55% (SE = 3%). Prognostic factors for a higher bladder relapse rate were: tumor multiplicity (p < 0.001), presence of ureteric obstruction (p = 0.001), and higher T stage (p 0.044). Distant failure occurred in 39 patients. The overall actuarial distant failure rate at 5 years was 28% (SE = 3%). Prognostic factors for a higher distant failure rate were: ureteric obstruction (p = 0.003) and higher T stage (p = 0.030). Conclusion: In our study, patients with invasive bladder TCC fell into distinct prognostic groups determined by the three independent factors, ureteric obstruction, tumor multiplicity, and T stage. These factors provided estimated risks of bladder relapse by 5 years which ranged from 34% to 91%. Knowledge of these prognostic factors can help in the selection of patients more suited for bladder preservation by definitive radiotherapy

  15. Small cell carcinoma of the urinary bladder diverticulum: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Wu Xu Dong

    2013-01-01

    Full Text Available Small cell carcinoma of the urinary bladder is very rare. Small cell carcinoma of the urinary bladder is a mass with swiftly aggressive and metastatic, and with a poor prognosis. Due to its scarcity, no forward-looking researches assessing the most effective treatment have been issued in the medical literature. It can happen either in connection with urothelial (transitional cell carcinoma or in a pure form. Its treatment should include surgery, chemotherapy and radiotherapy. In this article,we report a case occurring in a mixed form in the urinary bladder diverticulum and we concisely review the published literature with respect to the clinical manifestation, pathology,differential diagnosis, treatment and prognosis.

  16. Small cell carcinoma of the urinary bladder without gross hematuria: a case report.

    Science.gov (United States)

    Huang, Wanqiu; Luan, Yang; Jin, Lu; Wang, Tao; Chen, Ruibao; Liu, Zheng; Chen, Zhiqiang; Lan, Ruzhu

    2015-09-01

    Small cell carcinoma of the urinary bladder (SCCB) is a rare and aggressive form of bladder cancer with poor prognosis. Hematuria is the main symptom of this malignancy, and most patients have a history of smoking. The disease incidence of malignant bladder tumors in China is approximately 0.74%. Early and accurate diagnosis of SCCB can ensure timely and appropriate treatment of this malignant disease. Oncologic surgery is the standard treatment; however, it may not be a curative approach. Chemotherapy and/or radiotherapy should be performed following surgical removal. This case report describes a patient with a single neoplasm diagnosed as SCCB that arose because of recurrence of bladder cancer after bladder tumor resection. In contrast to previously reported cases, this patient had no gross hematuria and no history of smoking.

  17. Clinical outcome of primary small cell carcinoma of the urinary bladder

    Directory of Open Access Journals (Sweden)

    Hou CP

    2013-08-01

    Full Text Available Chen-Pang Hou,1,2 Yu-Hsiang Lin,1,2 Chien-Lun Chen,1,2 Phei-Lang Chang,1,2 Ke-Hung Tsui1,2 1Department of Urology, Chang Gung Memorial Hospital-Linko, Taiwan, Republic of China; 2College of Medicine, Chang Gung University, Taiwan, Republic of China Purpose: Primary small cell carcinoma of the urinary bladder is a rare malignant disease. It accounts for less than 1% of all urinary bladder carcinomas. The purpose of this study is to review the clinical features, the treatment modalities, and the overall survival of these patients. We also compare the clinical outcomes between patients of bladder small cell carcinoma (SCC and bladder urothelial carcinoma (UC. Materials and methods: We reviewed the charts of patients with bladder tumors from January 1995 to December 2012 in the Chang Gung Memorial Hospital. A total of 2421 malignant bladder tumor patients were reviewed and there were 18 patients who were diagnosed with primary bladder SCC. The patients' characteristics, including age, gender, smoking history, presented symptoms, tumor size, locations, clinical stages, treatment modalities, pathology appearance, recurrence conditions, and survival conditions were all recorded. We also compared the clinical outcomes and the overall survival rates between patients with bladder SCC and those with UC. Results: Bladder SCC accounted for about 0.74% of all bladder malignancies in our institution. The mean age at diagnosis was 70.67 years, and the male-to-female ratio was 2.6:1. Thirteen patients had a history of cigarette smoking. All patients presented with symptoms of gross hematuria, and three of them had bladder tamponade requiring blood clot evacuation by cystoscopy. Only one patient had T1 disease, ten patients had stage III disease, and seven patients had lymph node or distant metastasis (stage IV disease. The mean tumor size was 4.29 cm in diameter. For the majority (61.11% of patients, SCC coexisted with UC components. The average survival time

  18. Sixteen-slice multidetector computed tomographic virtual cystoscopy in the evaluation of a patient with suspected bladder tumor and history of bladder carcinoma operation.

    Science.gov (United States)

    Basak, Muzaffer; Ozkurt, Huseyin; Tanriverdi, Orhan; Cay, Esra; Aydin, Mustafa; Miroglu, Cengiz

    2009-01-01

    The purpose of this study was to evaluate the use of virtual cystoscopy performed with multidetector computed tomography (CT) in patients with suspected bladder tumors and histories of bladder carcinoma operation. Thirty-six patients (29 men and 7 women) with a mean age of 66 years (range, 24-88 years) with suspected bladder tumors and histories of bladder carcinoma operation were included in this prospective study. Virtual cystoscopy was performed by 16-slice multidetector CT scanner. The bladder was filled with diluted contrast material solution through a Foley catheter. Then, all patients underwent conventional cystoscopy examination. Two reviewers found 18 lesions detected by virtual cystoscopy by consensus, whereas 19 lesions were depicted by conventional cystoscopy. At virtual and conventional cystoscopies, the conditions of 3 patients, 2 with chronic inflammations and 1 with foreign body reaction, were wrongly diagnosed as tumors. At conventional cystoscopy, one patient's result was wrongly interpreted as normal. In pathologic evaluation, all tumors were diagnosed as transitional cell carcinoma. Bladder tumor can be noninvasively diagnosed using virtual cystoscopy. Use of virtual cystoscopy should be considered inpatients who present with hematuria or have histories of bladder carcinoma operation and are for follow-up because of its lesser complication risk and its being a less invasive, easily applied procedure without need of anesthesia. In the future, owing to the development of the CT technology and image processing technique, virtual cystoscopy may have a part in the detection of bladder cancer.

  19. Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

    DEFF Research Database (Denmark)

    Gui, Yaoting; Guo, Guangwu; Huang, Yi

    2011-01-01

    frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.......Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we...

  20. c-KIT positive schistosomal urinary bladder carcinoma are frequent but lack KIT gene mutations.

    Science.gov (United States)

    Shams, Tahany M; Metawea, Mokhtar; Salim, Elsayed I

    2013-01-01

    Urinary bladder squamous cell carcinoma (SCC), one of the most common neoplasms in Egypt, is attributed to chronic urinary infection with Schistosoma haematobium (Schistosomiasis). The proto-oncogene c-KIT, encoding a tyrosine kinase receptor and implicated in the development of a number of human malignancies, has not been studied so far in schistosomal urinary bladder SCCs. We therefore determined immunohistochemical (IHC) expression of c-KIT in paraffin sections from 120 radical cystectomies of SCCs originally obtained from the Pathology Department of Suez Canal University (Ismailia, Egypt). Each slide was evaluated for staining intensity where the staining extent of >10% of cells was considered positive. c-KIT overexpression was detected in 78.3% (94/120) of the patients, the staining extents in the tumor cells were 11-50% and >50% in 40 (42.6%) and 54 (57.4%) respectively. The positive cases had 14.9%, 63.8%, 21.3% as weak, moderate and strong intensity respectively. Patients with positive bilharzial ova had significantly higher c-KIT expression than patients without (95.2% vs. 38.9%, P=0.000). Mutation analysis of exons 9-13 was negative in thirty KIT positive cases. The high rate of positivity in SBSCC was one of the striking findings; However, CD117 may be a potential target for site specific immunotherapy to improve the outcome of this tumor.

  1. Local control rate and prognosis after sequential chemoradiation for small cell carcinoma of the bladder

    International Nuclear Information System (INIS)

    Meijer, Richard P.; Meinhardt, Wim; Poel, Henk G. van der; Rhijn, Bas W. van; Kerst, J. Martijn; Pos, Floris J.; Horenblas, Simon; Bex, Axel

    2013-01-01

    The objectives of this study were to assess the long-term outcome and the risk for local recurrence of patients with small cell carcinoma of the bladder (SCCB) treated with neoadjuvant chemotherapy followed by external beam radiotherapy (sequential chemoradiation). All consecutive patients with primary small cell carcinoma of the bladder (n=66), treated in our institution between 1993 and 2011 were retrospectively evaluated from an institutional database. Only patients with limited disease (Tx-4N0-1M0) small cell carcinoma of the bladder treated with sequential chemoradiation (n=27) were included in this study. Recurrence rates, overall survival and cancer-specific survival were analyzed using the Kaplan-Meier method. Median time to recurrence was 20 months, median overall survival 26 months, 5-year overall survival 22.2%, median cancer-specific survival 47 months and 5-year cancer-specific survival 39.6%. For complete responders after neoadjuvant chemotherapy (n=19), median cancer-specific survival was 52 months with a 5-year cancer-specific survival 45.9% versus a median cancer-specific survival of 22 months and 5-year cancer-specific survival 0.0% for incomplete responders (n=8; P=0.034). Eight patients (29.6%) underwent transurethral resections (TUR-BT) for local recurrences in the bladder. At the end of follow up, four patients had undergone cystectomy for recurrence of disease resulting in a bladder-preservation rate of 85.2%. Median time to local recurrence was 29 months and median time to distant recurrence was 10 months. Sequential chemoradiation for limited disease small cell carcinoma of the bladder results in a reasonable outcome with a high bladder preservation rate. Response to neoadjuvant chemotherapy represents a significant prognostic factor in this patient population. (author)

  2. Autopsy findings in surgical-radiotherapeutically treated bladder carcinoma - conclusions for optimization of radiotherapy

    International Nuclear Information System (INIS)

    Fueller, J.; Kob, D.; Fritzsche, V.

    1989-01-01

    Autopsy findings in patients with bladder carcinoma, treated by combined operation and radiotherapy, revealed tendencies of tumor spread as well as complications and late effects of radiotherapy. In 24.5% of the cases tumor tissue was found within the bladder and in 30.5% within the minor pelvis. Metastases were found in 24.1% in iliac lymph nodes, in 21.3% in abdominal lymph nodes. Liver, lungs, bones, and kidneys are main organs for hematological metastasizing. Little or undifferentiated carcinomas and squamous cell carcinomas showed a greater tendency to metastasize than highly and medium-differentiated ureteral carcinomas. The least radiotherapeutical complications and late effects were found in a fractionation with daily 1.5 Gy and a total dose of 60 Gy. (author)

  3. Carcinoma of Gall bladder with distant metastasis to breast parenchyma. Report of a case and review of literature

    International Nuclear Information System (INIS)

    Kumaran, D.; Anamalai, M.; Velu, U.; Julka, P.K.; Nambirajan, A.

    2016-01-01

    Background: Gall bladder carcinoma is one of the most common cancers in India. Gall bladder cancer with metastasis to the breast is very rare. Herein we intend to report a case of carcinoma gall bladder with breast metastasis and a short review of the literature. Methods: This report describes an interesting and unusual case of gall bladder carcinoma presenting with breast metastasis. Case report: A 38-year lady presented with complaints of right abdominal pain. Bilateral breast examination showed 2 2 cm palpable lump in the upper outer quadrant of the left breast. Contrast-enhanced CT of the abdomen and pelvis showed circumferential thickening of gall bladder with the loss of fat plane with the adjacent liver parenchyma. Biopsy from the breast lump was reported as metastatic adenocarcinoma compatible with primary in the gall bladder. Whole body PET-CT showed gall bladder mass with abdominal and pelvic nodes with metastasis to liver, left breast, C7 vertebral body and left supra-clavicular node. She was diagnosed to have disseminated carcinoma gall bladder with liver, breast and supraclavicular nodal metastasis. She received palliative chemotherapy with gemcitabine and carboplatin and radiotherapy to C7 vertebra. After receiving 3 cycles of chemotherapy, chemotherapy was changed to the second line with single agent capecitabine. In spite of two lines of chemotherapy, she succumbed to disease progression and expired. Conclusion: There are limited examples of gall bladder adenocarcinoma with simultaneous metastasis to breast in the English literature. Our case showed an unusual dissemination of gall bladder cancer

  4. Appraisal of diagnostic ability of UCA1 as a biomarker of carcinoma of the urinary bladder.

    Science.gov (United States)

    Srivastava, A K; Singh, P K; Rath, S K; Dalela, D; Goel, M M; Bhatt, M L B

    2014-11-01

    Initial diagnosis of carcinoma of the urinary bladder remains to be a challenge. Urine cytology, as an adjunct to cystoscopy, is less sensitive for low-grade tumors. Urothelial cancer associated 1 (UCA1) is a novel non-coding RNA gene, which plays a pivotal role in bladder cancer progression. Our aim is to investigate the significance of urinary UCA1 for the non-invasive diagnosis of transitional cell carcinoma (TCC) of the urinary bladder. We examined UCA1 expression in a bladder cancer cell line (T24) and in urine of 28 healthy individuals, 46 patients of non-malignant disorders, and 117 cases (69 primary and 48 recurrent cases) of histologically proven TCC prior to transurethral resection by using real-time PCR and compared it with voided urinary cytology. UCA1 expression was found in T24 cell line and also found to be significantly higher in the cancer group as compared to the controls (p0.05). UCA1 can be used as a non-invasive diagnostic biomarker for TCC bladder as an adjunct to cytology in the early diagnosis of primary urinary bladder cancer.

  5. 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.

  6. Status of Her2 over expression in muscle invasive urothelial bladder carcinoma: Report of 21 cases

    Directory of Open Access Journals (Sweden)

    Nesrine Mejri

    2014-01-01

    Four patients died from disease, one of them had Her2 3+ score. Conclusion: Her2 overexpression can be observed in muscle invasive urothelial bladder carcinoma in an important number of patients. Evaluation criteria must be standardized, especially with heterogeneous cases. Metastases tests can also readdress the expression of Her2, which gives the patient a supplementary therapeutic tool.

  7. Case report of metastatic invasive breast lobular carcinoma to the urinary bladder.

    Science.gov (United States)

    Al Ibraheemi, Ahmed A

    2016-01-01

    Breast cancer is the most common cancer in women except skin cancer. The common metastatic sites include lymph node, lung, liver and bone. However, metastasis to the bladder is extremely rare. To our knowledge, this is the first case of breast cancer metastasis to urinary bladder in Jordan which is reported. Nine years after the initial diagnosis of lobular breast carcinoma, the patient suffered from left side leg edema; Ultrasonography and Computed tomography scanning showed thickening of posterior bladder wall and bilateral hydronephrosis. The biopsy of the bladder confirmed metastatic lesion from the breast. In contrast to the primary tumor, bladder metastasis showed negative expression of estrogen (ER) and progesterone (PR) receptors. However, Her2neu test was negative in both. The reported case confirms that bladder metastasis from breast cancer tend to occur late after the diagnosis of the primary tumor. Furthermore, bladder metastasis can be asymptomatic and heterogeneous in ER and PR expression in comparison with the primary tumor. This report supports the need for careful follow-up and early intervention whenever such clinical situation is suspected. This report supports further evaluation of receptor status at time of metastasis.

  8. Lymphoepithelioma-like carcinoma of the urinary bladder: A case report.

    Science.gov (United States)

    Laforga, Juan B; Gasent, Joan M

    We report a case of lymphoepithelioma-like carcinoma of the urinary bladder in an elderly female patient. A 97-year old woman presented with hematuria, and an ultrasonographic urinary study showed a localized tumor in the trigone region of the urinary bladder. A transurethral resection revealed a mixed tumor formed by high-grade transitional carcinoma and lymphoepithelioma-like carcinoma that had infiltrated into the muscular propria. We describe the clinicopathological, morphological and immunohistochemical features of this tumor and briefly discuss its differential diagnosis and biological behavior. Copyright © 2016 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Immunohistochemical analysis of the role and relationship between Notch-1 and Oct-4 expression in urinary bladder carcinoma.

    Science.gov (United States)

    Abdou, Asmaa Gaber; El-Wahed, Moshira Mohammed Abd; Kandil, Mona Abd-Elhalim; Samaka, Rehab Monir; Elkady, Noha

    2013-10-01

    Most tumors contain a minor population of cancer stem cells that are responsible for tumor heterogeneity, resistance to therapy and recurrence. Oct-4 is a transcription factor responsible for self-renewal of stem cells, whereas the Notch family of receptors and ligands may play a pivotal role in the regulation of stem cell maintenance and differentiation. This study aimed at an evaluation of Oct-4 and Notch-1 expression in both carcinoma and stromal cells of 83 cases of primary bladder carcinoma and to study the relationship between them. Notch-1 was expressed in carcinoma and stromal cells of all malignant cases, where expression in both cell types was correlated with parameters indicating differentiation, such as low grade (p bladder carcinoma, such as poor differentiation (p = 0.001), high proliferation (p bladder carcinoma, where they may cooperate in the progression of bladder carcinoma by acquiring aggressive features, such as a liability for recurrence and dissemination. Notch-1 is also expressed in both carcinoma cells and stromal cells of bladder carcinoma. Although they could share in enhancing differentiation, stromal expression of Notch-1 may have a bad impact, possibly through up-regulation of the active nuclear form of Oct-4 in carcinoma cells. © 2013 APMIS Published by Blackwell Publishing Ltd.

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

    Directory of Open Access Journals (Sweden)

    Deepika Kanojia

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

  11. Vitronectin in human breast carcinomas

    DEFF Research Database (Denmark)

    Aaboe, Mads; Offersen, Birgitte Vrou; Christensen, Anni

    2003-01-01

    We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters and in the subendothe......We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters...... and in the subendothelial area of some blood vessels. In normal tissue, vitronectin had a homogeneous periductal occurrence, with local accumulation much lower than that in the carcinomas. Using a new solid phase radioligand assay, the vitronectin concentrations of extracts of carcinomas and normal breast tissue were...... is not synthesised locally in breast tissue but derived by leakage from vessels, followed by extracellular accumulation in patterns distinctly different in carcinomas and normal tissue. The observation of a high vitronectin content in the carcinomas and its localisation in the tissue contributes to the clarification...

  12. Selective arterial embolization for control of haematuria secondary to advanced or recurrent transitional cell carcinoma of the bladder.

    LENUS (Irish Health Repository)

    Halpenny, D

    2014-05-02

    Haematuria is a common symptom in patients with advanced transitional cell carcinoma of the bladder. We report our experience of selective pelvic embolization using gelfoam as an embolic agent to treat intractable haematuria in these patients.

  13. Forced diuresis 18F-fluorodeoxyglucose positron emission tomography/contrast enhanced in detection of carcinoma of urinary bladder diverticulum

    International Nuclear Information System (INIS)

    Soundararajan, Ramya; Singh, Harmandeep; Arora, Saurabh; Nayak, Brusabhanu; Shamim, Shamim Ahmed; Bal, Chandrasekhar; Kumar, Rakesh

    2015-01-01

    Urinary bladder diverticular carcinomas are uncommon with a lesser incidence of 0.8–10% and its diagnosis still remains a challenge. Cystoscopy is the most reliable method, but evaluating diverticulum with narrow orifices is difficult. Before the initiation of appropriate treatment, proper detection of bladder diverticular carcinoma and its locoregional and distant sites of involvement is necessary. Here, we present a case of 48-year-old male with urinary bladder diverticular carcinoma detected by forced diuretic 18 F-fluorodeoxyglucose positron emission tomography/computerized tomography ( 18 F-FDG PET/CT). This case also highlights the significance of forced diuretic 18 F-FDG PET/CT in the detection, staging, and response evaluation of bladder diverticular carcinoma

  14. Risk factors for transitional cell carcinoma of urinary bladder: a hospital based study

    International Nuclear Information System (INIS)

    Fayyaz, A.; Ilyas, M.; Qayyum, A.

    2011-01-01

    Objective: The objective of the study was to determine the role of various known risk factors for the development of Transitional cell carcinoma (TCC) of urinary bladder in our set up. Study design: Case control study Place and duration of the study: Department of Radiology CMH Rawalpindi, from March 2007 to December 2007. Material and methods: 70 patients with TCC urinary bladder were included in the study. 70 controls were included. The patients were enquired about the risk factors. The data was analysed on SPSS version 12. Odds ratio for each factor was carried out. p value of < 0.05 was considered statistically significant. Results: Smoking was the most important factor in the development of TCC of urinary bladder with odds ratio of 3:1. Driving was the next common factor. Low socioeconomic conditions appear to be an important factor in our set up. The role of chemicals in industrial work could not be established. Conclusion: Differences from the West exist regarding the etiological factors for the development of TCC of urinary bladder. Males outnumber the females by a significant ratio. Smoking is an important factor in the development of TCC of urinary bladder. Most bladder cancers arise in low socioeconomic group in our set up. (author)

  15. A case of brain and leptomeningeal metastases from urothelial carcinoma of the bladder.

    Science.gov (United States)

    Erhamamcı, S; Reyhan, M; Altinkaya, N

    2014-01-01

    Brain metastases are unusual from urethelial carcinoma of bladder and particularly the occurrence of leptomeningeal metastases is extremely rare, with few cases described in the literature. We present a case of a 45-year-old man with a rare brain metastases as the first metastatic manifestation secondary to urethelial carcinoma of bladder followed by leptomeningeal metastases without any other organ involvement. Eleven months after the diagnosis of high-grade urethelial carcinoma of bladder (T2N0M0), the patient was detected having brain metastases by MRI. FDG PET/CT images for the metastatic evaluation showed no abnormal FDG uptake elsewhere in the body except the brain. Histopathology examination from brain lesion demonstrated the cerebral lesion to be a metastatic urothelial carcinoma. Two months later, the patient was diagnosed to have leptomeningeal metastases by MRI. Our patient's condition gradually worsened, and he died 3 months after the diagnosis of leptomeningeal metastases. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  16. 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.

  17. 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.

  18. Female, Black, and Unmarried Patients Are More Likely to Present With Metastatic Bladder Urothelial Carcinoma.

    Science.gov (United States)

    Klaassen, Zachary; DiBianco, John M; Jen, Rita P; Evans, Austin J; Reinstatler, Lael; Terris, Martha K; Madi, Rabii

    2016-10-01

    Although there are well-established risk factors for the diagnosis of bladder cancer, there is no consensus regarding risk factors for presentation of advanced or metastatic disease at diagnosis. The objective of this study was to identify the demographic and clinical factors associated with metastasis at diagnosis in patients with bladder urothelial carcinoma. Patients diagnosed with bladder urothelial carcinoma from 2004 to 2010 were identified in the Surveillance, Epidemiology, and End Results (SEER) database (n = 108,417). The primary outcome was metastatic disease at the time of diagnosis. Demographic and socioeconomic variables were analyzed, and multivariable logistic regression models were performed to generate odds ratios (OR) for factors associated with metastasis at diagnosis. Of patients with bladder cancer, 3018 (2.8%) had metastasis at diagnosis and 105,399 (97.2%) had nonmetastatic disease. Patients with metastatic disease at diagnosis were more frequently female (29.6% vs. 23.6%, P vs. 5.0%, P unmarried (44.1% vs. 32.5%, P vs. male, OR 1.21), black race (vs. white, OR 1.71), unmarried (vs. married, OR 1.46), unemployed (OR 1.02), and foreign-born status (OR 1.01). Female gender, black race, unmarried, unemployed, and foreign-born status are independently associated with metastasis at diagnosis for bladder urothelial carcinoma. All clinicians should be aware of these potential health care disparities in order to involve social services and other support mechanisms in efforts to improve early care. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Treatment Trends and Outcomes of Small-Cell Carcinoma of the Bladder

    Energy Technology Data Exchange (ETDEWEB)

    Koay, Eugene J. [Baylor College of Medicine, Houston, Texas (United States); MD Anderson Cancer Center, Houston, Texas (United States); Teh, Bin S., E-mail: bteh@tmh.org [Methodist Hospital, Houston, Texas (United States); Methodist Hospital Research Institute, Houston, Texas (United States); Paulino, Arnold C.; Butler, E. Brian [Methodist Hospital, Houston, Texas (United States); Methodist Hospital Research Institute, Houston, Texas (United States)

    2012-05-01

    Purpose: Treatment for small-cell carcinoma of the bladder is largely guided by case reports, retrospective reviews, and small prospective trials. This study aimed to study outcomes using a large population-based database. Methods: The Surveillance, Epidemiology, and End Results-Medicare database (1991-2005) was used to analyze how different treatment combinations of specific bladder surgeries, chemotherapy, and radiation affected patient outcomes. Trends in the use of these combinations over time were also analyzed. Results: A total of 533 patients were retrieved from the database. A bladder-sparing approach involving transurethral resection of the bladder tumor (TURBT) combined with chemotherapy and radiation yielded no significant difference in overall survival compared with patients undergoing at least a cystectomy (of whom over 90% received radical cystectomy) with chemotherapy (p > 0.05). The analysis of treatment trends indicated that these two general strategies for cure combined to account for fewer than 20% of patients. A majority of patients (54%) received TURBT as their only surgical treatment, and a subset analysis of these patients indicated that chemotherapy played a role in all stages of disease (p < 0.05) whereas radiation improved overall survival in regional-stage disease (p < 0.05). Conclusion: Relatively few patients with small-cell carcinoma of the bladder receive potentially curative therapies. Chemotherapy should be a major component of treatment. Cystectomy and bladder-sparing approaches represent two viable strategies and deserve further investigation to identify the patients who may benefit from organ preservation or not. In addition, the role of radiation in regional-stage disease should be investigated further, because it positively affects survival after TURBT.

  20. Treatment Trends and Outcomes of Small-Cell Carcinoma of the Bladder

    International Nuclear Information System (INIS)

    Koay, Eugene J.; Teh, Bin S.; Paulino, Arnold C.; Butler, E. Brian

    2012-01-01

    Purpose: Treatment for small-cell carcinoma of the bladder is largely guided by case reports, retrospective reviews, and small prospective trials. This study aimed to study outcomes using a large population-based database. Methods: The Surveillance, Epidemiology, and End Results–Medicare database (1991–2005) was used to analyze how different treatment combinations of specific bladder surgeries, chemotherapy, and radiation affected patient outcomes. Trends in the use of these combinations over time were also analyzed. Results: A total of 533 patients were retrieved from the database. A bladder-sparing approach involving transurethral resection of the bladder tumor (TURBT) combined with chemotherapy and radiation yielded no significant difference in overall survival compared with patients undergoing at least a cystectomy (of whom over 90% received radical cystectomy) with chemotherapy (p > 0.05). The analysis of treatment trends indicated that these two general strategies for cure combined to account for fewer than 20% of patients. A majority of patients (54%) received TURBT as their only surgical treatment, and a subset analysis of these patients indicated that chemotherapy played a role in all stages of disease (p < 0.05) whereas radiation improved overall survival in regional-stage disease (p < 0.05). Conclusion: Relatively few patients with small-cell carcinoma of the bladder receive potentially curative therapies. Chemotherapy should be a major component of treatment. Cystectomy and bladder-sparing approaches represent two viable strategies and deserve further investigation to identify the patients who may benefit from organ preservation or not. In addition, the role of radiation in regional-stage disease should be investigated further, because it positively affects survival after TURBT.

  1. The value of bladder mapping and prostatic urethra biopsies for detection of carcinoma in situ (CIS).

    Science.gov (United States)

    Gudjónsson, Sigurdur; Bläckberg, Mats; Chebil, Gunilla; Jahnson, Staffan; Olsson, Hans; Bendahl, Pär-Ola; Månsson, Wiking; Liedberg, Fredrik

    2012-07-01

    It is well known that CIS is a major risk factor for muscle-invasive bladder cancer and that this entity can be difficult to diagnose. Taking cold-cup mapping biopsies from different areas of the bladder (BMAP) is commonly used in patients at risk of harbouring CIS. The diagnostic accuracy of this approach has not been assessed until now. By using the CIS found in the cystoprostatectomy specimen as an indicator of the true occurrence of CIS and comparing that with the findings of BMAP, it is clear that the sensitivity of BMAP to detect CIS when present is low and that negative findings should be considered unreliable. To assess the value of bladder mapping and prostatic urethra biopsies for detection of urothelial carcinoma in situ (CIS). CIS of the urinary bladder is a flat high-grade lesion of the mucosa associated with a significant risk of progression to muscle-invasive disease. CIS is difficult to identify on cystoscopy, and definite diagnosis requires histopathology. Traditionally, if CIS is suspected, multiple cold-cup biopsies are taken from the bladder mucosa, and resection biopsies are obtained from the prostatic urethra in males. This approach is often called bladder mapping (BMAP). The accuracy of BMAP as a diagnostic tool is not known. Male patients with bladder cancer scheduled for cystectomy underwent cold-cup bladder biopsies (sidewalls, posterior wall, dome, trigone), and resection biopsies were taken from the prostatic urethra. After cystectomy, the surgical specimen was investigated in a standardised manner and subsequently compared with the BMAP biopsies for the presence of CIS. The histopathology reports of 162 patients were analysed. CIS was detected in 46% of the cystoprostatectomy specimens, and multiple (≥2) CIS lesions were found in 30%. BMAP (cold-cup bladder biopsies + resection biopsies from the prostatic urethra) provided sensitivity of 51% for any CIS, and 55% for multiple CIS lesions. The cold-cup biopsies for CIS in the bladder

  2. An updated review on primary signet-ring cell carcinoma of the urinary bladder and report of a case

    DEFF Research Database (Denmark)

    Lendorf, Maria Elisabeth; Dohn, Line Hammer; Á Dunga, Bara

    2018-01-01

    OBJECTIVE: The aim of the present study was to emphasize the critical importance of the clinician's awareness of signet-ring cell carcinoma (SRCC) of the urinary bladder, a rare and aggressive disease entity. MATERIALS AND METHODS: A review of the current literature was conducted and a classic case...... of advanced SRCC of the urinary bladder is reported, clearly demonstrating the severity of this disease and the imperative need for standardized recommendations for the diagnostic work-up and management of urinary bladder SRCC. RESULTS: The prognosis for patients with SRCC of the urinary bladder is poor...

  3. Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young H. [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Apolo, Andrea B. [Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Agarwal, Piyush K.; Bottaro, Donald P., E-mail: dbottaro@helix.nih.gov [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2014-11-25

    There is mounting evidence of oncogenic hepatocyte growth factor (HGF)/Met signaling in urothelial carcinoma (UC) of the bladder. The effects of three kinase inhibitors, cabozantinib, crizotinib and EMD1214063, on HGF-driven signaling and cell growth, invasion and tumorigenicity were analyzed in cultured UC cell lines. SW780 xenograft growth in SCID and human HGF knock-in SCID (hHGF/SCID) mice treated with cabozantinib or vehicle, as well as tumor levels of Met and pMet, were also determined. Met content was robust in most UC-derived cell lines. Basal pMet content and effector activation state in quiescent cells were low, but significantly enhanced by added HGF, as were cell invasion, proliferation and anchorage independent growth. These HGF-driven effects were reversed by Met inhibitor treatment. Tumor xenograft growth was significantly higher in hHGF/SCID mice vs. SCID mice and significantly inhibited by cabozantinib, as was tumor phospho-Met content. These studies indicate the prevalence and functionality of the HGF/Met signaling pathway in UC cells, suggest that paracrine HGF may contribute to UC tumor growth and progression, and that support further preclinical investigation of Met inhibitors for the treatment of UC is warranted.

  4. Prognostic factors in invasive bladder carcinoma treated by combined modality protocol (organ-sparing approach)

    International Nuclear Information System (INIS)

    Matos, Tadeja; Cufer, Tanja; Cervek, Jozica; Borstnar, Simona; Kragelj, Borut; Zumer-Pregelj, Mirjana

    2000-01-01

    Purpose: The results of bladder sparing approach for the treatment of muscle-invasive bladder cancer, using a combination of transurethral resection (TUR), chemotherapy, and radiotherapy, are encouraging. The survival of patients treated by this method is similar to the survival of patients treated by radical cystectomy. The aim of our study was to find out which pretreatment characteristics influence the survival of patients treated by organ sparing approach that would enable us to identify the patients most suitable for this type of treatment. Methods and Materials: The prognostic value of different factors, such as age, gender, performance status, hemoglobin level, clinical stage, histologic grade, presence of obstructive uropathy, and completeness of TUR, has been studied in 105 patients with invasive bladder cancer, who received a bladder sparing treatment in the period from 1988 to 1995. They were treated with a combination of TUR, followed by 2-4 cycles of methotrexate, cisplatinum, and vinblastine polychemotherapy. In complete responders the treatment was completed by radiotherapy (50 Gy to the bladder and 40 Gy to the regional lymph nodes), whereas nonresponders underwent cystectomy whenever feasible. Results: Our study has confirmed an independent prognostic value of performance status, histologic grade, and obstructive uropathy, for the disease-specific survival (DSS) of bladder cancer patients treated by a conservative approach. We believe that performance status best reflects the extent of disease and exerts significant influence on the extent and course of treatment, while obstructive uropathy is a good indicator of local spread of the disease, better than clinical T-stage. Our finding that histologic grade is one of the strongest prognostic factors shows that tumor biology also is a very important prognostic factor in patients treated by conservative approach. Conclusion: Patients with muscle-invasive bladder cancer who are most likely to benefit

  5. Alterations to the protein profile of bladder carcinoma cell lines induced by plant extract MINA-05 in vitro.

    Science.gov (United States)

    Nguyen-Khuong, Terry; White, Melanie Y; Hung, Tzong-Tyng; Seeto, Shona; Thomas, Melissa L; Fitzgerald, Anna M; Martucci, Carlos E; Luk, Sharon; Pang, Shiu-Fu; Russell, Pamela J; Walsh, Bradley J

    2009-04-01

    Bladder cancer (BLCa) is a severe urological cancer of both men and women that commonly recurs and once invasive, is difficult to treat. MINA-05 (CK Life Sciences Int'l, Hong Kong) is a derivative of complex botanical extracts, shown to reduce cellular proliferation of bladder and prostate carcinomas. We tested the effects of MINA-05 against human BLCa cell sublines, B8, B8-RSP-GCK, B8-RSP-LN and C3, from a transitional cell carcinoma, grade IV, to determine the molecular targets of treatment by observing the cellular protein profile. Cells were acclimatised for 48 h then treated for 72 h with concentrations of MINA-05 reflecting 1/2 IC(50), IC(50) and 2 x IC(50) (n = 3) or with vehicle, (0.5% DMSO). Dose-dependant changes in protein abundance were detected and characterised using 2-dimensional electrophoresis and MS. We identified 10 proteins that underwent changes in abundance, pI and/or molecular mass in response to treatment. MINA-05 was shown to influence proteins across numerous functional classes including cytoskeletal proteins, energy metabolism proteins, protein degradation proteins and tumour suppressors, suggesting a global impact on these cell lines. This study implies that the ability of MINA-05 to retard cellular proliferation is attributed to its ability to alter cell cycling, metabolism, protein degradation and the cancer cell environment.

  6. Metastasis of Gastric Signet-Ring Cell Carcinoma to the Urinary Bladder: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Kerem Okutur

    2015-01-01

    Full Text Available Although signet-ring cell (SRC adenocarcinoma is commonly seen in the stomach, it is a very rarely seen histologic entity in the bladder. It is difficult to distinguish primary SRC adenocarcinoma of the bladder from bladder metastasis of SRC carcinoma of the stomach only based on histological findings. In such cases, clinical findings and immunohistochemical studies may be helpful. We present here a 48-year-old male patient presenting with hematuria and abdominal pain. Computerised tomography of the patient revealed a gastric mass, peritoneal involvement, and thickening of the bladder wall, and histopathological analysis revealed SRC adenocarcinoma in both of the endoscopic biopsies taken from the stomach and bladder. Immunohistochemical analyses confirmed the diagnosis of SRC adenocarcinoma of the bladder secondary to gastric cancer.

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

    DEFF Research Database (Denmark)

    Zieger, Karsten; Marcussen, Niels; Borre, Michael

    2009-01-01

    Bladder cancer develops through different pathways, provisionally entitled "papillary" and "invasive." Carcinoma in situ (CIS) is thought to be the precursor of invasive bladder cancer. However, little is known about chromosomal alterations of these clinically important lesions......, and the relationship between chromosomal alterations and the different pathways. We laser-microdissected 12 CIS and 4 dysplasia samples concomitant to invasive bladder cancer. We determined genome-wide chromosome copy number changes and loss of heterozygosity (LOH) using Mapping 10K SNP microarrays. We further...... examined 48 high-risk non-muscle-invasive bladder cancers using SNP microarrays to reveal characteristic changes correlated with the CIS-phenotype. DNA copy-number changes were further validated using QPCR in 77 independent tumor samples. CIS was found to be chromosomal unstable in 8 of 12 cases...

  8. External Beam Radiotherapy for Focal Lymphoepithelioma-Like Carcinoma in the Urinary Bladder: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Nobuhiro Kushida

    2015-01-01

    Full Text Available Lymphoepithelioma is a malignant epithelial tumor in the nasopharynx characterized by prominent lymphoid infiltration. Carcinomas that resemble lymphoepitheliomas have been called lymphoepithelioma-like carcinomas and have been reported in other organs. A tumor in the bladder is categorized by the percentage of the total area occupied by the lymphoepithelioma-like carcinoma pattern, with the prognosis dependent on the percentage. We present an 81-year-old man with stage 3 chronic obstructive pulmonary disease and a history of aortic aneurysm repair. The computed tomography scans indicated thickening and irregularity of the bladder wall, with left external iliac lymph node metastasis. His diagnosis was bladder cancer, and the clinical stage was evaluated as T3N1M0. Transurethral resection of the bladder tumor was performed, and the pathological specimen showed that the tumor was composed of undifferentiated malignant cells with sheets and nests arranged in a syncytial pattern, as well as an urothelial carcinoma lesion. A prominent lymphoid reaction accompanied the tumor. The pathological diagnosis was focal-type lymphoepithelioma-like carcinoma containing a component of urothelial carcinoma G3>G2. His general condition was such that he could not tolerate radical cystectomy or systemic chemotherapy. External beam radiotherapy (total 60 Gy was given to the bladder, including the lymph node metastatic lesion. No cancer recurrence was detected by regular follow-up computed tomography and cystoscopy. He eventually died of other causes 48 months later. Although treatment for focal lymphoepithelioma-like carcinoma generally requires multifocal therapies, in the present case, the bladder became tumor free. We also summarize previously reported lymphoepithelioma-like carcinoma cases treated with radiotherapy.

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

    Science.gov (United States)

    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

  10. The nested variant of bladder transitional cell carcinoma: Review of 12 cases and review of the literature.

    Science.gov (United States)

    Carrion-Ballardo, C J; Gala-Solana, L; Portillo-Martin, J A; Azueta-Etxebarria, A; Truan-Cacho, D; Campos-Juanatey, F

    2015-01-01

    The nested variant of bladder transitional cell carcinoma is extremely rare and has a different biological behavior to other bladder tumors. The aim of this study is to analize if their behavior is as aggressive as has been described in the literature. Review of 12 diagnosed cases with nested variant of bladder transitional cell carcinoma and analysis of demographic characteristics, clinical presentation, tumor characteristics, treatment options, analysis of recurrence and cancer-specific survival between January 1997 and December 2010 in our hospital. 50% of the cases had a pathologic stage ≥T2, with grade of differentiation G2 (50%) or G3 (50%). After the pathological result of the TUR (transurethral resection) Bladder, 5 cases underwent radical cystoprostatectomy, 3 a second TUR bladder and 4 cases with treatment chemotherapy and/or radiotherapy (RT). Five out of 12 cases (41.7%) died due to bladder cancer and 3 died (25%) of other causes (urinary sepsis, respiratory failure, renal failure). With a median follow up of 40 months, the overall survival was 50% and cancer-specific survival of 65.6%. The nested variant of bladder transitional cell carcinoma is a disease with an advanced-stage presentation, with high recurrence and mortality rates despite the use of different treatments. So far there is not a clinical practice guideline for this variety of urothelial tumor. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. 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

  12. Zoledronic acid use in patients with bone metastases from renal cell carcinoma or bladder cancer.

    Science.gov (United States)

    Saad, Fred; Eastham, James A

    2010-06-01

    Approximately 30% of patients with renal cell carcinoma (RCC) and 40% of patients with bladder cancer develop bone metastases that can disrupt normal bone homeostasis and place patients at risk for potentially life-limiting skeletal-related events (SREs). In the absence of bone-directed therapies, patients with RCC may experience up to four SREs per year. In patients with bone metastases from RCC or bladder cancer, zoledronic acid (ZOL) significantly reduced the risk of SREs compared with placebo. In addition to its bone-protective effects, preclinical and early clinical evidence indicates that ZOL prevents tumor progression. For example, retrospective subset analysis in patients with RCC indicated that ZOL extended time to disease progression and demonstrated a trend toward improved overall survival compared with placebo. Additionally, a study in patients with bone metastases from bladder cancer demonstrated that ZOL improved 1-year overall survival compared with placebo. Bone metastases place a heavy burden on patients with RCC or bladder cancer, and early, continuous treatment with ZOL may provide anticancer benefits in addition to important patient quality of life. 2010. Published by Elsevier Inc.

  13. 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%.

  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. 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.

  16. Solitary brain metastasis as an initial manifestation of gall bladder carcinoma

    Directory of Open Access Journals (Sweden)

    Kamlesh Kumar Harsh

    2015-01-01

    Full Text Available Gallbladder cancer is a common malignancy in Northern India, and it accounts for 2-4% of all malignant gastrointestinal tumors. It is an aggressive tumor with early dissemination to liver and lymph nodes and associated with poor prognosis. Systemic metastases from gall bladder carcinoma (Ca frequently occur; however, metastatic involvement of the central nervous system is rare and late manifestation and remains an ominous sign. Initial presentation of gall bladder Ca with brain metastasis is rare. We report a case of 65-year-old women who initially presented with a solitary brain metastasis from an adenocarcinoma of the gallbladder, which was diagnosed incidentally when the patient presented with headache, vomiting, and right temporal region swelling. Palliative chemotherapy and cranial radiotherapy were prescribed. She is symptom-free from 3 months after the completion of the treatment.

  17. Incidental Diagnosis of Carcinoma of the Bladder Due to Uptake of 99mTc-MDP

    International Nuclear Information System (INIS)

    Damle, Nishikant A; Pandey, Dinesh Chand; Gautam, Awadhesh Kumar; Subbarao, Kiran; Singh, Prabhjot; Mishra, Rohini; Das, Nitendra Lal; Pandey, Dinesh Chand; Gautam, Awadhesh Kumar

    2012-01-01

    A bone scan was per-formed using 740 MBq (29 mCi) 99 mTc-MDP. Whole-body planar images were acquired 3 h after injection (Fig. 1). Soft tissue uptake of 99 mTc-MDP is described in various benign and malignant conditions. It is known to accumulate in adenocarcinoma of lung, primary breast cancer, and colonic carcinoma among others. The postulated causes of 99 mTc-MDP uptake in extraosseous neoplasms are numerous and include tumor vascularity, inflammation, local pH factors, altered calcium metabolism, hormonal influences and cell wall damage. Our case shows that TCC of the bladder was incidentally diagnosed due to MDP uptake in multiple bladder polyps detected on a bone scan done for low backache in an 80-year-old man

  18. Myasthenia Gravis After Nivolumab Therapy for Squamous Cell Carcinoma of the Bladder.

    Science.gov (United States)

    Chang, Elaine; Sabichi, Anita L; Sada, Yvonne H

    2017-04-01

    Checkpoint inhibitors have become standard therapy for multiple cancers, and their use will increase in the next year as regulatory approvals for additional indications are expected. It is essential for clinicians to be aware of the potential for rare immune-related adverse effects. Here, we report the case of a new diagnosis of myasthenia gravis (MG) after the use of nivolumab for squamous cell carcinoma of the bladder. A review the literature identified 10 cases of MG diagnosed after programmed cell death protein 1 inhibitor therapy. This is the first case, to our knowledge, reported in association with bladder cancer. The precise diagnosis of MG has important implications on management, as treatment with steroids can transiently worsen myasthenia in nearly 50% of cases.

  19. PPARγ-independent induction of growth arrest and apoptosis in prostate and bladder carcinoma

    International Nuclear Information System (INIS)

    Chaffer, Christine L; Thomas, David M; Thompson, Erik W; Williams, Elizabeth D

    2006-01-01

    Although PPARγ antagonists have shown considerable pre-clinical efficacy, recent studies suggest PPARγ ligands induce PPARγ-independent effects. There is a need to better define such effects to permit rational utilization of these agents. We have studied the effects of a range of endogenous and synthetic PPARγ ligands on proliferation, growth arrest (FACS analysis) and apoptosis (caspase-3/7 activation and DNA fragmentation) in multiple prostate carcinoma cell lines (DU145, PC-3 and LNCaP) and in a series of cell lines modelling metastatic transitional cell carcinoma of the bladder (TSU-Pr1, TSU-Pr1-B1 and TSU-Pr1-B2). 15-deoxy-prostaglandin J 2 (15dPGJ2), troglitazone (TGZ) and to a lesser extent ciglitazone exhibited inhibitory effects on cell number; the selective PPARγ antagonist GW9662 did not reverse these effects. Rosiglitazone and pioglitazone had no effect on proliferation. In addition, TGZ induced G0/G1 growth arrest whilst 15dPGJ2 induced apoptosis. Troglitazone and 15dPGJ2 inhibit growth of prostate and bladder carcinoma cell lines through different mechanisms and the effects of both agents are PPARγ-independent

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    and carcinoma in situ (CIS) and for predicting disease recurrence and progression. EXPERIMENTAL DESIGN: We analyzed tumors from 404 patients diagnosed with bladder cancer in hospitals in Denmark, Sweden, England, Spain, and France using custom microarrays. Molecular classifications were compared with pathologic....... CONCLUSION: This multicenter validation study confirms in an independent series the clinical utility of molecular classifiers to predict the outcome of patients initially diagnosed with non-muscle-invasive bladder cancer. This information may be useful to better guide patient treatment....

  1. 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

  2. Cost-effective treatment of low-risk carcinoma not invading bladder muscle.

    Science.gov (United States)

    Green, David A; Rink, Michael; Cha, Eugene K; Xylinas, Evanguelos; Chughtai, Bilal; Scherr, Douglas S; Shariat, Shahrokh F; Lee, Richard K

    2013-03-01

    Study Type - Therapy (cost effectiveness analysis) Level of Evidence 2a What's known on the subject? and What does the study add? Bladder cancer is one of the costliest malignancies to treat throughout the life of a patient. The most cost-effective management for low-risk non-muscle-invasive bladder cancer is not known. The current study shows that employing cystoscopic office fulguration for low-risk appearing bladder cancer recurrences can materially impact the cost-effectiveness of therapy. In a follow-up protocol where office fulguration is routinely employed for low-risk bladder cancers, peri-operative intravesical chemotherapy may not provide any additional cost-effectiveness benefit. To examine the cost-effectiveness of fulguration vs transurethral resection of bladder tumour (TURBT) with and without perioperative intravesical chemotherapy (PIC) for managing low-risk carcinoma not invading bladder muscle (NMIBC). Low-risk NMIBC carries a low progression rate, lending support to the use of office-based fulguration for small recurrences rather than traditional TURBT. A Markov state transition model was created to simulate treatment of NMIBC with vs without PIC, with recurrence treated by formal TURBT vs treatment with fulguration. Costing data were obtained from the Medicare Resource Based Relative Value Scale. Data regarding the success of PIC were obtained from the peer-reviewed literature, as were corresponding utilities for bladder cancer-related procedures. Sensitivity analyses were performed. At 5-year follow-up, a strategy of fulguration without PIC was the most cost-effective (mean cost-effectiveness = US $654.8/quality-adjusted life year), despite a lower recurrence rate with PIC. Both fulguration strategies dominated each TURBT strategy. Sensitivity analysis showed that fulguration without PIC dominated all other strategies when the recurrence rate after PIC was increased to ≥14.2% per year. Similarly, the cost-effectiveness of TURBT becomes more

  3. 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

  4. Pseudoaneurysm embolization and vasopressin infusion for lower gastrointestinal bleeding due to recurrence of urinary bladder carcinoma.

    Science.gov (United States)

    Kakizawa, Hideaki; Toyota, Naoyuki; Mita, Koji; Fujimura, Yoshio; Hieda, Masashi; Hirai, Nobuhiko; Tachikake, Toshihiro; Ito, Katsuhide

    2006-05-01

    We report a case that was successfully treated for massive lower gastrointestinal (LGI) bleeding due to a recurrent urinary bladder carcinoma. Treatment consisted of combination therapy including embolization of an inferior gluteal artery (IGA) pseudoaneurysm and low-dose arterial vasopressin infusion via a sigmoid artery (SA). A 57-year-old man presented with life-threatening sudden, massive LGI bleeding due to an obturator lymph node (LN) metastasis from a urinary bladder carcinoma. Computed tomography showed that the LN recurrence had invaded all the way to the sigmoid colon, and there was a pseudoaneurysm with extravasation inside the recurrence. An angiogram revealed a left IGA pseudoaneurysm. We therefore excluded the pseudoaneurysm by embolization with microcoils. Following this treatment the bleeding decreased, but intermittent LGI bleeding continued. Endoscopic examination showed the tumor with a huge ulcer inside the colonic lumen, and continuous oozing was confirmed. A second angiogram showed no recurrence of the IGA pseudoaneurysm and no apparent findings of bleeding. Then a 3F microcatheter was placed in the SA selectively using a coaxial catheter system, and vasopressin was infused at a rate 0.05 U/min for 12 h. Bleeding completely ceased 2 days later. There were no signs of ischemic gastrointestinal complications. Massive LGI bleeding has not recurred in 5 months.

  5. Rare Association of Anti-Hu Antibody Positive Paraneoplastic Neurological Syndrome and Transitional Cell Bladder Carcinoma

    Directory of Open Access Journals (Sweden)

    S. Lukacs

    2012-01-01

    Full Text Available Introduction. Paraneoplastic encephalomyelitis (PEM and subacute sensory neuronopathy (SSN are remote effects of cancer, usually associated with small-cell lung carcinoma and positive anti-Hu antibody. We describe the rare association of bladder transitional cell carcinoma (TCC with anti-Hu antibody positivity resulting in this paraneoplastic neurological syndrome. Patient. A 76-year-old female presented with bilateral muscle weakness and paraesthesia of the upper and lower limbs in a length-dependent “glove and stocking” distribution. Central nervous system symptoms included cognitive problems, personality change, and truncal ataxia. Case notes and the literature were reviewed. Result. Autoantibody screening was positive for anti-Hu antibody (recently renamed antineuronal nuclear antibody 1, ANNA-1. The diagnosis of PEM and SSN was supported by MRI and lumbar puncture results. A superficial bladder TCC was demonstrated on CT and subsequently confirmed on histology. No other primary neoplasm was found on full-body imaging. The neurological symptoms were considered to be an antibody-mediated paraneoplastic neurological syndrome and improved after resection of the tumour. Discussion. The association of anti-Hu positive paraneoplastic neurological syndrome and TCC has not been described in the literature previously. We emphasize the need for detailed clinical examination and the importance of a multidisciplinary thought process and encourage further awareness of this rare association.

  6. Magnetic resonance imaging of urinary bladder carcinoma: tumor staging and gadolinium contrast-enhanced imaging

    International Nuclear Information System (INIS)

    Doringer, E.; Joos, H.; Forstner, R.; Schmoller, H.

    1992-01-01

    Forty-nine patients with urinary bladder carcinomas underwent pre-operative examinations using magnetic resonance (MR) imaging. The results of the MR examinations were correlated with the clinical-pathological findings following transurethral resection (TUR) and bimanual palpation (n = 47) or radical cystectomy (n = 2). The results of pre-contrast MR tumor staging (T1, T2), viewing stages Tis-T2 collectively, and subsequent to separate assessments of stages T3b-T4b, were correct 76.6% of the time. Gadolinium-DTPA (Gd-DTPA) contrast-enhanced examinations (pre-contrast T1 and after Gd-DTPA) showed a staging accuracy rate of 85.7%. T2-weighted images did not indicate any advantage when compared to T1-weighted images following Gd-DTPA. The signal intensity ratios of tumor/fat and tumor/muscle tissue were measured on T1-weighted pre-contrast images and following Gd-DTPA and then evaluated statistically, whereby the increased tumor signal intensity was statistically significant (Wilcoxon test, P < 0.01). Due to the relatively short examination time needed for T1-weighted images and the specific tumor enhancement, the administration of Gd-DTPA proves valuable in the diagnosis of bladder carcinomas. T2-weighted images are not necessary. (orig.)

  7. Studies on the cellular immune response in patients with upper urinary tract carcinoma compawed with those in patients with bladder carcinoma and it's postoperative change

    International Nuclear Information System (INIS)

    Sakai, Shunsuke

    1980-01-01

    Non-specific cellular immunity of patients with upper urinary tract carcinoma was studied by PPD reaction (in vivo or in vitro), lymphocytes subpopulation and macrophage migration inhibition test and the results were compared with those of patients with bladder carcinoma or benign urological diseases. 1) The preoperative cellular immunity of the malignant tumor group gave low values as compared to that in the benign disease group. Although the cellular immunity of patients with renal cell carcinoma showed no difference in the points of their grade and stage, significant differences were noted in patients with bladder carcinoma. The patients with renal pelvic and ureter carcinoma appeared to be similar to the patients with bladder carcinoma in the aspects of immune reactions. 2) In the majority of patients with upper urinary tract and bladder carcinoma, the cellular immunity after complete removal of the carcinoma gave an increased value of each marker as compared to the preoperative value. 3) The cellular immunity after irradiation decreased in the majority of the cases in terms of PPD reaction and T-cell ratio in lymphocyte subpopulation. Irradiation of 4000 - 6000 Rad. showed greater influence on T-cell than on B-cell, but influence of irradiation on cellular immunity was not different by irradiation dose. 4) The cellular immunity indicated decreased values for one to two months after discontinuation of irradiation, but then it showed a tendency to increase in terms of PPD and lymphocytes subpopulation in the patients with satisfactory postoperative courses. 5) Through the pre and postoperative courses, the immunity of the carcinomatous stage seems to be reflected better by the T-cell ratio than by the absolute number of T-cell. It is likely that macrophage migration inhibition test shows much sharper reaction than PPD reaction. (author)

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

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    Lucio Dell’Atti

    2015-03-01

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

  9. Targeting of alpha-v integrins reduces malignancy of bladder carcinoma.

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    Geertje van der Horst

    Full Text Available Low survival rates of metastatic cancers emphasize the need for a drug that can prevent and/or treat metastatic cancer. αv integrins are involved in essential processes for tumor growth and metastasis and targeting of αv integrins has been shown to decrease angiogenesis, tumor growth and metastasis. In this study, the role of αv integrin and its potential as a drug target in bladder cancer was investigated. Treatment with an αv integrin antagonist as well as knockdown of αv integrin in the bladder carcinoma cell lines, resulted in reduced malignancy in vitro, as illustrated by decreased proliferative, migratory and clonogenic capacity. The CDH1/CDH2 ratio increased, indicating a shift towards a more epithelial phenotype. This shift appeared to be associated with downregulation of EMT-inducing transcription factors including SNAI2. The expression levels of the self-renewal genes NANOG and BMI1 decreased as well as the number of cells with high Aldehyde Dehydrogenase activity. In addition, self-renewal ability decreased as measured with the urosphere assay. In line with these observations, knockdown or treatment of αv integrins resulted in decreased metastatic growth in preclinical in vivo models as assessed by bioluminescence imaging. In conclusion, we show that αv integrins are involved in migration, EMT and maintenance of Aldehyde Dehydrogenase activity in bladder cancer cells. Targeting of αv integrins might be a promising approach for treatment and/or prevention of metastatic bladder cancer.

  10. Primary signet-ring cell carcinoma of the urinary bladder successfully managed with cisplatin and gemcitabine: a case report

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    El Ammari Jalal Eddine

    2013-02-01

    Full Text Available Abstract Introduction Primary signet-ring cell carcinoma of the urinary bladder is a rare variant of mucus-producing adenocarcinoma constituting approximately 0.5% to 2.0% of all primary carcinomas of the bladder. This tumor initially presents as a high-grade, high-stage lesion and diffusely invades the bladder wall without forming intraluminal growth. The patients have no specific symptoms, which leads to delayed diagnosis and poor prognosis. Case presentation We report the case of a 51-year-old Moroccan Berber man consulting for gross hematuria. Ultrasonography and a computed tomography scan found a bladder tumor diffusely invading the bladder wall. A histopathological examination of the tumor chips from a transurethral resection of the bladder revealed signet-ring cell adenocarcinoma. The gastrointestinal tract exploration did not reveal any other tumor localization. A radical cystectomy and adjuvant cisplatin and gemcitabine chemotherapy were therefore performed resulting in 18 months of survival without metastasis and a good quality of life within that time. Conclusion The rarity and the successful management with carboplatin and gemcitabine as adjuvant chemotherapy of this entity, which is rarely reported in the literature, are two remarkable characteristics described in this case report.

  11. Lymphoepithelioma-like carcinoma of the urinary bladder: A case report and review of systemic treatment options

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    Nicholas M Pantelides

    2012-01-01

    Full Text Available Lymphoepithelioma-like carcinoma (LELC of the urinary bladder is a rare variant, which can occur in a pure form or in conjunction with transitional cell carcinoma. Owing to the scarcity of reported cases, the optimum treatment is yet to be defined, although the benefits of chemotherapy are increasingly recognised. We present a case of a 64-year-old man with pure LELC, treated with trans-urethral resection of the bladder tumor (TURBT and primary gemcitabine and platinum-based chemotherapy. He remained free of disease at six-month follow-up cystoscopy. The case adds to the growing evidence for the efficacy of chemotherapy, coupled with TUR, as part of a bladder-preserving treatment option for LELC.

  12. Stereological estimates of nuclear volume in the prognostic evaluation of primary flat carcinoma in situ of the urinary bladder

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Jacobsen, F

    1991-01-01

    Primary, flat carcinoma in situ of the urinary bladder is rare and its behaviour is unpredictable. The aim of this retrospective study was to obtain base-line data and investigate the prognostic value of unbiased, stereological estimates of the volume-weighted mean nuclear volume, nuclear vv, in ...

  13. Intravenous chemotherapy combined with intravesical chemotherapy to treat T1G3 bladder urothelial carcinoma after transurethral resection of bladder tumor: results of a retrospective study

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    Zhang Y

    2016-01-01

    Full Text Available Yu Zhang,1,* Linguo Xie,1,* Tao Chen,1,* Wanqin Xie,2 Zhouliang Wu,1 Hao Xu,1 Chen Xing,1 Nan Sha,1 Zhonghua Shen,1 Yunkai Qie,1 Xiaoteng Liu,1 Hailong Hu,1 Changli Wu1 1Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, 2Key Laboratory of Genetics and Birth Health of Hunan Province, The Family Planning Research Institute of Hunan Province, Changsha, People’s Republic of China *These authors contributed equally to this work Objective: The management of stage 1 and grade 3 (T1G3 bladder cancer continues to be controversial. Although the transurethral resection of bladder tumor (TURBT followed by intravesical chemotherapy is a conservative strategy for treatment of T1G3 bladder cancer, a relatively high risk of tumor recurrence and progression remains regarding the therapy. This study aimed to compare the efficacy of intravenous chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder cancer after TURBT surgery. Methods: We retrospectively reviewed the cases of 457 patients who were newly diagnosed with T1G3 bladder urothelial carcinoma between January 2009 and March 2014. After TURBT, 281 patients received intravesical chemotherapy alone, whereas 176 patients underwent intravesical chemotherapy in combination with intravenous chemotherapy. Tumor recurrence and progression were monitored periodically by urine cytology and cystoscopy in follow-up. Recurrence-free survival and progression-free survival of the two chemotherapy strategies following TURBT were analyzed. Univariable and multivariable Cox hazards analyses were performed to predict the prognostic factors for tumor recurrence and progression. Results: The tumor recurrence rate was 36.7% for patients who received intravesical chemotherapy alone after TURBT, compared with 19.9% for patients who received intravenous chemotherapy combined with intravesical chemotherapy after

  14. Contrast-enhanced computed tomography of the primary tumor in muscle invasive carcinoma of the urinary bladder

    International Nuclear Information System (INIS)

    Sager, E.M.

    1991-01-01

    Patients with muscle invasive carcinoma of the urinary bladder were examined with contrast-enhanced CT of the primary tumor. A specially designed technique was developed to increase the diagnostic potential of CT. The most important points about the technique were controlled filling of the bladder, the use of thin slices, series of scans before and after intravenous injection of contrast medium, and long scanning times in the precontrast series. The absorbed dose to the patient resulting from the new technique was found to be within the range of the dose from urography or barium enema. This dose was considered to be acceptable given the diagnostic gain of the procedure. Features of irradiated bladder tumors were analysed to find which parameter correlated with persistent malignancy. High contrast enhancement of a tumor relative to the bladder wall was found to be the best indicator of a malignant tumour after irradiation. 127 refs

  15. Clear-cell variant urothelial carcinoma of the bladder: a case report and review of the literature

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    Hossein Tezval

    2012-10-01

    Full Text Available Clear cell variants of transitional cell carcinomas (TCC of the bladder are extremely rare tumors. Only 6 cases have been reported until now. We report of a 67 year old man who presented with fast growing tumor disease. While initial diagnosis showed localized bladder tumor, final histopathology revealed pT4, G3, L1 urothelial carcinoma with clear cell differentiation. No more than 14 weeks after initial diagnosis the patient died from multi-organ failure after unsuccessful salvage laparotomy which showed massive tumor burden within the pelvis and peritoneal carcinosis. This case demonstrated an extremely fast tumor growth. Therefore, patients with clear cell urothelial carcinoma should be treated vigorously and without time delay. We present a case of clear cell variant of TCC which exhibited an extremely aggressive behavior. To our knowledge this is the fifth report of this rare disease.

  16. Quantitative histopathology in the prognostic evaluation of patients with transitional cell carcinoma of the urinary bladder

    DEFF Research Database (Denmark)

    Sasaki, M; Sørensen, Flemming Brandt; Fukuzawa, S

    1993-01-01

    BACKGROUND: Morphologic grading of malignancy is considered to be of prognostic value in patients with transitional cell carcinomas of the urinary bladder (TCC). This qualitative approach is, however, associated with low reproducibility. Grading of malignancy can be carried out on a reproducible......, quantitative scale. METHODS: A retrospective, prognostic study of 110 patients treated for TCC in clinical Stages Ta-T4 (median follow-up time, 6 years) was performed, evaluating various grading techniques. Unbiased estimates of the volume-weighted mean nuclear volume (nuclear vV), nuclear volume fraction...... of nuclear vV are prognostically superior to morphologic grading of malignancy in noninvasive TCC, whereas both morphologically and quantitatively based malignancy grading are without prognostic value in invasive TCC....

  17. Quantitative histopathology in the prognostic evaluation of patients with transitional cell carcinoma of the urinary bladder

    DEFF Research Database (Denmark)

    Sasaki, M; Sørensen, Flemming Brandt; Fukuzawa, S

    1993-01-01

    BACKGROUND: Morphologic grading of malignancy is considered to be of prognostic value in patients with transitional cell carcinomas of the urinary bladder (TCC). This qualitative approach is, however, associated with low reproducibility. Grading of malignancy can be carried out on a reproducible......, quantitative scale.METHODS: A retrospective, prognostic study of 110 patients treated for TCC in clinical Stages Ta-T4 (median follow-up time, 6 years) was performed, evaluating various grading techniques. Unbiased estimates of the volume-weighted mean nuclear volume (nuclear vV), nuclear volume fraction...... of nuclear vV are prognostically superior to morphologic grading of malignancy in noninvasive TCC, whereas both morphologically and quantitatively based malignancy grading are without prognostic value in invasive TCC....

  18. Diagnosis of urinary bladder carcinoma by MR: Improvement through Gd-DTPA?

    International Nuclear Information System (INIS)

    Sparenberg, A.; Hamm, B.; Samberger, V.; Wolf, K.J.; Hammerer, P.

    1991-01-01

    85 patients suffering from urinary bladder carcinoma were examined by magnetic resonance imaging in a prospective study. Following precontrast diagnosis, 15 patients were given an intravesicular application of gadolinium-DTPA (Gd-DTPA). Another 35 patients received an intravenous bolus of Gd-DTPA. A diagnostic advantage was achieved in only 2 of 15 tumours by using intravesicular contrast application. Compared to the precontrast diagnosis, a 14% improvement from 69% (precontrast) to 83% (contrast medium) was seen with Gd-DTPA applied intravenously in the diagnosis of the tumour stage. The diagnostic gain lies in the improved tumour recognition, the improved demarcation of papillary, non-muscle-infiltrating tumours and in the more definite diagnosis of infiltration into neighbouring organs and the pelvic wall. Demarcation of perivesicular fatty infiltration is rendered more difficult by Gd-DTPA. (orig.) [de

  19. Metabolic syndrome and the risk of urothelial carcinoma of the bladder: a case-control study

    International Nuclear Information System (INIS)

    Montella, Maurizio; Di Maso, Matteo; Crispo, Anna; Grimaldi, Maria; Bosetti, Cristina; Turati, Federica; Giudice, Aldo; Libra, Massimo; Serraino, Diego; La Vecchia, Carlo; Tambaro, Rosa; Cavalcanti, Ernesta; Ciliberto, Gennaro; Polesel, Jerry

    2015-01-01

    The Metabolic syndrome (MetS) is an emerging condition worldwide, consistently associated with an increased risk of several cancers. Some information exists on urothelial carcinoma of the bladder (UCB) and MetS. This study aims at further evaluating the association between the MetS and UCB. Between 2003 and 2014 in Italy, we conducted a hospital-based case-control study, enrolling 690 incident UCB patients and 665 cancer-free matched patients. The MetS was defined as the presence of at least three of the four selected indicators: abdominal obesity, hypercholesterolemia, hypertension, and diabetes. Odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) for MetS and its components were estimated through multiple logistic regression models, adjusting for potential confounders. Patients with MetS were at a 2-fold higher risk of UCB (95 % CI:1.38–3.19), compared to those without the MetS. In particular, ORs for bladder cancer were 2.20 (95 % CI:1.42–3.38) for diabetes, 0.88 (95 % CI: 0.66-1.17) for hypertension, 1.16 (95 % CI: 0.80-1.67) for hypercholesterolemia, and 1.63 (95 % CI:1.22–2.19) for abdominal obesity. No heterogeneity in risks emerged across strata of sex, age, education, geographical area, and smoking habits. Overall, 8.1 % (95 % CI: 3.9-12.4 %) of UCB cases were attributable to the MetS. This study supports a positive association between the MetS and bladder cancer risk

  20. Loss of MTUS1/ATIP expression is associated with adverse outcome in advanced bladder carcinomas: data from a retrospective study

    International Nuclear Information System (INIS)

    Rogler, Anja; Lehmann, Jan; Petsch, Sabrina; Hartmann, Arndt; Stoehr, Robert; Hoja, Sabine; Giedl, Johannes; Ekici, Arif B; Wach, Sven; Taubert, Helge; Goebell, Peter J; Wullich, Bernd; Stöckle, Michael

    2014-01-01

    Seventy percent of all bladder tumours tend to recur and need intensive surveillance, and a subset of tumours progress to muscle-invasive and metastatic disease. However, it is still difficult to find the adequate treatment for every individual patient as it is a very heterogeneous disease and reliable biomarkers are still missing. In our study we searched for new target genes in the critical chromosomal region 8p and investigated the potential tumour suppressor gene candidate MTUS1/ATIP in bladder cancer. MTUS1 was identified to be the most promising deleted target gene at 8p in aCGH analysis with 19 papillary bladder tumours. A correlation with bladder cancer was further validated using immunohistochemistry of 85 papillary and 236 advanced bladder tumours and in functional experiments. Kaplan-Meier analysis and multivariate Cox-regression addressed overall survival (OS) and disease-specific survival (DSS) as a function of MTUS1/ATIP expression. Bivariate correlations investigated associations between MTUS1/ATIP expression, patient characteristics and histopathology. MTUS1 expression was analysed in cell lines and overexpressed in RT112, where impact on viability, proliferation and migration was measured. MTUS1 protein expression was lost in almost 50% of all papillary and advanced bladder cancers. Survival, however, was only influenced in advanced carcinomas, where loss of MTUS1 was associated with adverse OS and DSS. In this cohort, there was also a significant correlation of MTUS1 expression and histological subtype: positive expression was detected in all micropapillary tumours and aberrant nuclear staining was detected in a subset of plasmocytoid urothelial carcinomas. MTUS1 was expressed in all investigated bladder cell lines and overexpression in RT112 led to significantly decreased viability. MTUS1 is a tumour suppressor gene in cultured bladder cancer cells and in advanced bladder tumours. It might represent one new target gene at chromosome 8p and can be

  1. Blood tests and prognosis in bladder carcinomas treated with definitive radiotherapy

    International Nuclear Information System (INIS)

    Hannisdal, E.; Fossa, S.D.; Host, H.

    1993-01-01

    The value of some commonly recorded blood tests as prognostic factors in patients with bladder carcinomas treated with definitive radiotherapy has been assessed. This study included 202 consecutive patients (T2, n=46; T3, n=82 and T4, n=74) treated during the period 1980-1987. The median total dose received was 56 Gy [50-67] and the median cumulative radiation effect was 1750 reu (radiation effect unit) (1515-1823). The blood tests examined in survival analyses were erythrocyte sedimentation rate (ESR), hemoglobin (Hb), leucocyte and thrombocyte count, alkaline phosphatase (ALP), γ-glutamyltransferase (GT), lactate dehydrogenase (LD), creatinine and albumin. In the univariate survival analyses six blood tests were significant prognostic factors (ESR, albumin, creatinine, Hb, ALP and GT). In the multivariate analysis of all 202 patients, the following five variables were significantly associated with shorter survival: T4 tumors, ESR > 30 mm/h, albumin 400 U/I and age >75 years. Our conclusion is that several commonly recorded blood tests are powerful prognostic factors in bladder cancer treated with definitive radiotherapy. These tests can replace other more expensive laboratory investigations used for prognostication. (author). figs. tabs

  2. 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.

  3. Role of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Diagnostic Evaluation of Carcinoma Urinary Bladder: Comparison with Computed Tomography

    International Nuclear Information System (INIS)

    Chakraborty, Dhritiman; Mittal, Bhagwant Rai; Kashyap, Raghava; Mete, Utham Kumar; Narang, Vikram; Das, Ashim; Bhattacharya, Anish; Khandelwal, Niranjan; Mandal, Arup K.

    2014-01-01

    Bladder carcinoma is the most frequent tumor of the urinary tract and accounts 7% of all malignancies in men and 2% of all malignancies in women. This retrospective study was carried out to assess the diagnostic utility of F18-fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the imaging evaluation of bladder carcinoma. Seventy-seven consecutive patients diagnosed to have carcinoma urinary bladder referred for F18-FDG PET/CT were included in this study. Thirty-four patients were for initial staging after transurethral biopsy and remaining 43 patients were for restaging. All patients also underwent CT scan of the abdomen and pelvis. PET/CT findings were correlated with diagnostic CT scan and histopathological findings. In 30 of the 34 patients for initial staging, both PET/CT and CT confirmed the primary lesion in the bladder. Histopathology report was available in 23 patients. Lymph nodes FDG uptake reported to be metastatic in 10/23 patients while CT detected lymph node metastasis in 12 patients. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy have been calculated to be 87.5%, 80%, 70%, 92%, 82% for PET/CT and 66%, 57%, 50%, 72%, 60% for CT respectively. PET/CT detected metastatic disease in 8 patients whereas CT detected in 4 patients. Of the 43 patients for restaging, local recurrence was detected in 24 patients on both PET/CT and CT. Histopathology report was available in 17 patients. Sensitivity, specificity, PPV, NPV and accuracy were 85%, 60%, 60%, 85%, 70% for PET/CT and 80%, 50%, 40%, 85%, 58% for CT respectively. Nineteen patients were detected to have metastatic disease by PET/CT, whereas CT detected metastases in 11 patients. F-18 FDG PET/CT is a very useful modality in pre-operative staging and monitoring after surgery, chemotherapy or radiotherapy of patients with carcinoma urinary bladder

  4. Bladder transitional cell carcinoma: correlation of contrast enhancement on computed tomography with histological grade and tumour angiogenesis

    International Nuclear Information System (INIS)

    Xie, Q.; Zhang, J.; Wu, P.-H.; Jiang, X.-Q.; Chen, S.-L.; Wang, Q.-L.; Xu, J.; Chen, G.-D.; Deng, J.-H.

    2005-01-01

    AIM: To investigate the correlation between the degree of contrast enhancement of bladder cancer in the early enhanced phase of helical computed tomography (CT) and microvessel density (MVD), vascular endothelial growth factor (VEGF) and histological grade. MATERIALS AND METHODS: Sixty-five patients with transitional cell carcinoma of the bladder were examined by incremental unenhanced CT and helical CT at 40-45 s after initiation of intravenous administration of contrast medium before surgery. The CT density in Hounsfield units of bladder carcinomas were measured in the middle of the maximum diameter section of the cancer lesions on unenhanced and enhanced CT. The degree of contrast enhancement of the tumour was determined as the absolute increase in Hounsfield units. Histological grade, VEGF and MVD were analysed for each cancer. The Pearson and Spearman correlation tests were used to determine the strength of the relationships between CT enhancement and histological grade, VEGF expression and MVD. RESULTS: Different degrees of enhancement were observed in 91 cancers during the early enhanced phase of helical CT. Mean MVDs and mean CT enhancing values of different histological grade groups were statistically different (p<0.001). A positive correlation was found in the CT-enhancing value of bladder cancer and MVD (Pearson correlation test; r=0.938, p<0.001) and histological grade (Spearman rank correlation; r=0.734, p<0.001). VEGF of bladder cancer did not correlate with the change in CT attenuation (Spearman rank correlation; r=0.087, p=0.410) and MVD (Spearman rank correlation, r=0.103, p=0.330). CONCLUSION: In bladder cancer, the degree of contrast enhancement during the early enhanced helical CT is correlated with the MVD and histological grade of tumour. It is possible that MVD is the histopathological basis of early contrast enhancement of bladder cancer

  5. Incidentally Detected Penile Metastases in a Patient of Carcinoma Urinary Bladder on Follow-up FDG PET/CT.

    Science.gov (United States)

    Parida, Girish Kumar; Tripathy, Sarthak; Roy, Shambo Guha; Singhal, Abhinav; Das, Chandanjyoti; Shamim, Shamim Ahmed

    2017-05-01

    Penis is an extremely uncommon site for metastases to occur and is often associated with very grave prognosis. Most of the secondary tumors originating in the penis have primaries from prostate, urinary bladder, and gastrointestinal tract. We hereby report a 65-year-old man, known case of carcinoma urinary bladder, who came for FDG PET/CT for metastatic workup. PET/CT study revealed FDG-avid mass lesion in the root and shaft of the penis, making it suggestive of metastases, which was confirmed later by MRI correlation.

  6. 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

  7. Bladder chondrosarcoma plus urothelial carcinoma in recurred transitional cell carcinoma of the upper urinary tract: a case report and literature review.

    Science.gov (United States)

    Cho, Min Hyun; Kim, Sung Han; Park, Weon Seo; Joung, Jae Young; Seo, Ho Kyung; Chung, Jinsoo; Lee, Kang Hyun

    2016-10-20

    Sarcomatoid urothelial carcinoma (SUC) is a rare malignant neoplasm of the urinary bladder comprising 0.2-0.6 % of all histological bladder tumor subtypes. It presents as a high-stage malignancy and exhibits aggressive biological behavior, regardless of the treatment employed. It is defined as histologically indistinguishable from sarcoma and as a high-grade biphasic neoplasm with malignant epithelial and mesenchymal components. The mean age of patients presenting with SUC is 66 years, and the male-to-female ratio is 3:1. In addition, gross hematuria is usually present. The prognosis of SUC is poorer than that of typical urothelial carcinoma because of uncertainty concerning the optimal treatment regimen. We report the case of a 77-year-old woman with SUC containing a chondrosarcoma component who, 12 years previously, had undergone a nephroureterectomy for pT3N0M0 ureter cancer of the contralateral upper urinary tract. From the 4th year of follow-up after nephroureterectomy, multiple recurrent bladder tumors staged as Ta transitional cell carcinoma developed, and six transurethral resections of the bladder (TURB) with multiple intravesical instillations were performed without any evidence of metastases and upper tract recurrences. In 2015, a right partial distal ureterectomy and an additional TURB were performed due to a papillary mass at the right contralateral ureterovesical junction of the bladder, which was confirmed as a high-grade pT1 transitional cell carcinoma. After a further 2 years of follow-up, total pelvic exenteration with an ileal conduit diversion was performed to remove the mass, which was a pT4N0M0 tumor composed of carcinomatous and sarcomatous elements compatible with a sarcomatoid carcinoma including grade 3 transitional cell carcinoma and chondrosarcoma. Immunohistochemical examination showed that tumor cells were positive for vimentin and p63 and negative for NSE and Cd56 markers. In the first postoperative month, a metastatic lung nodule

  8. Neoadjuvant and adjuvant chemotherapy for locally advanced bladder carcinoma. Development of novel bladder preservation approach, Osaka Medical College regimen

    International Nuclear Information System (INIS)

    Azuma, Haruhito; Inamoto, Teruo; Takahara, Kiyoshi; Ibuki, Naokazu; Nomi, Hayahito; Yamamoto, Kazuhiro; Narumi, Yoshihumi; Ubai, Takanobu

    2012-01-01

    Cisplatin-based chemotherapy has been widely used in a neoadjuvant as well as adjuvant setting. Furthermore, trimodal approaches including complete transurethral resection of the bladder tumor followed by combined chemotherapy and radiation have generally been performed as bladder preservation therapy. However, none of the protocols have achieved a 5-year survival rate of more than 70%. Additionally, the toxicity of chemotherapy and/or a decreased quality of life due to urinary diversion cannot be ignored, as most patients with bladder cancer are elderly. We therefore newly developed the novel trimodal approach of ''combined therapy using balloon-occluded arterial infusion of anticancer agent and hemodialysis with concurrent radiation, which delivers an extremely high concentration of anticancer agent to the site of a tumor without systemic adverse effects (''Osaka Medical College regimen'' referred to as the OMC regimen). We initially applied the OMC regimen as neoadjuvant chemotherapy for locally advanced bladder cancer. However, since more than 85% of patients with histologically-proven urothelial cancer achieved complete response with no evidence of recurrence after a mean follow-up of 170 (range 21-814) weeks, we have been applying the OMC-regimen as a new approach for bladder sparing therapy. We summarize the advantage and/or disadvantage of chemotherapy in neoadjuvant as well as adjuvant settings, and show the details of our newly developed bladder sparing approach OMC regimen in this review. (author)

  9. Resolution of hypercalcemia of malignancy following radical cystectomy in a patient with paraneoplastic syndrome associated with urothelial carcinoma of the bladder

    Directory of Open Access Journals (Sweden)

    Alfredo Harb-De La Rosa

    2015-01-01

    Full Text Available Hypercalcemia of malignancy is a common finding associated with different types of cancers; however, its association with urothelial carcinoma of the bladder is rare. We report a case of a 69-year-old male with nonmetastatic urothelial carcinoma of the bladder who developed hypercalcemia that failed to respond to medical management, but resolved completely after undergoing resection of the tumor through radical cystectomy.

  10. A novel combination of multiple primary carcinomas: Urinary bladder transitional cell carcinoma, prostate adenocarcinoma and small cell lung carcinoma- report of a case and review of the literature

    Directory of Open Access Journals (Sweden)

    Giannikaki Elpida

    2005-07-01

    Full Text Available Abstract Background The incidence of multiple primary malignant neoplasms increases with age and they are encountered more frequently nowadays than before, the phenomenon is still considered to be rare. Case presentation We report a case of a man in whom urinary bladder transitional cell carcinoma, metachronous prostate adenocarcinoma and small cell lung carcinoma were diagnosed within an eighteen-month period. The only known predisposing factor was that he was heavy smoker (90–100 packets per year. The literature on the phenomenon of multiple primary malignancies in a single patient is reviewed and the data is summarized. Conclusion It is important for the clinicians to keep in mind the possibility of a metachronous (successive or a synchronous (simultaneous malignancy in a cancer patient. It is worthy mentioning this case because clustering of three primary malignancies (synchronous and metachronous is of rare occurrence in a single patient, and, to our knowledge, this is the first report this combination of three carcinomas appearing in the same patient.

  11. Initial Results of Bladder Preserving Approach by Chemo-Radiotherapy in Patients with Muscle Invading Transitional Cell Carcinoma

    International Nuclear Information System (INIS)

    Aboziada, M.A.; Hamza, H.; Abdlrahem, A.M.

    2009-01-01

    This study was conducted to test the efficacy and tolerability of trimodality treatment for invasive bladder cancer and to test the possibility of bladder sparing. Methods: This study had been carried out on 50 patients with transitional cell carcinoma (TCC) stage T2- T3 tumors with adequate performance status and renal function. All patients were subjected to maximum transurethral resection of bladder tumors (TURBT). Patients were then subjected to chemo-radiation that was executed in two treatment phases. Phase I was external radiotherapy in the form of 46 Gy /23 fractions /5 weeks to whole pelvis with concurrent cisplatin 40 mg/m 2 weekly. Phase II was 20 Gy /10 fractions /2 weeks to the bladder tumor with concurrent cisplatin 40 mg/m2 weekly. After phase I, patients who had complete response (CR) or partial response (PR) were subjected to phase II and patients who had stationary disease (SD) were subjected to salvage cystectomy. After the end of treatment, patients who had CR were subjected to bladder preservation. Radiological and cystoscopic reevaluation was done to assess the tumor response after phase I and phase II. After completion of the scheduled treatment, patients were under follow up for clinical examination, radiological, and cystoscopic assessment. Results: The treatment schedule was tolerable and was associated with infrequent incidence of moderate toxicity that was easily controlled without interruption of treatment. Bladder preservation was achieved in 72% of patients. The actuarial relapse free survival and overall survival at a median follow up 18 months for patients who were candidate for bladder preservation were 81% and 100%; respectively. Invasive recurrence (16%) sal-Jvaged with cystectomy and superficial recurrence (6%) successfully treated with Bacilles bilie de Calmette- Guerin. Conclusions: This study indicates that in spite of a relatively small number of patients and short follow-up period; the trimodality treatment could be an

  12. 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....

  13. 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

  14. The forecasting of radiation injuries of the urinary bladder and rectum in patients with uterine cervix carcinoma

    International Nuclear Information System (INIS)

    Zharinov, G.M.; Gabelov, A.A.

    1984-01-01

    The frequency and degree of severity of radiation in unjuries of the urinary bladder and rectum after combined treatment of 725 patients with uterine cercix carcigoma are analysed. A quantitative index was worked out permi-- tting one to give an ob ective evaluation of the degree of early radiation reactions of the ad acent organs. The determination of the ''radiation injuries prognosis index'' (RIPI) makes it possible to forecast the occurence and degree of severity of late radiation injuries of the urinary bladder and rectum. The evaluation of RIPI mean values in the patients' groups provides an opportunity to oompare the damaging effect of different methods and regiment directly in the process of radiation therapy. The above method improves the potentialities of the forecasting of radiation injuries of the urinary bladder and rectum in patients with uterine cervix carcinoma

  15. Human papillomavirus DNA in aerodigestive squamous carcinomas ...

    African Journals Online (AJOL)

    A series of 10 oesophageal and 10 laryngeal squamous carcinomas was examined by means of immuno cytochemistry and in situ DNA hybridisation to demonstrate human papillomavirus (HPV) infection. Changes in the epithelium adjacent to the carcinoma were found in 5 of 10 oesophageal and 7 of 10 laryngeal ...

  16. Bioinformatic identification of FGF, p38-MAPK, and calcium signalling pathways associated with carcinoma in situ in the urinary bladder

    International Nuclear Information System (INIS)

    Herbsleb, Malene; Christensen, Ole F; Thykjaer, Thomas; Wiuf, Carsten; Borre, Michael; Ørntoft, Torben F; Dyrskjøt, Lars

    2008-01-01

    Carcinoma in situ (CIS) is believed to be a precursor of invasive bladder cancer. Identification of CIS is a valuable prognostic factor since radical treatment strategies can be offered these patients before the disease becomes invasive. We developed a pathway based classifier approach to predict presence or absence of CIS in patients suffering from non muscle invasive bladder cancer. From Ingenuity Pathway Analysis we considered four canonical signalling pathways (p38 MAPK, FGF, Calcium, and cAMP pathways) with most coherent expression of transcription factors (TFs) across samples in a set of twenty-eight non muscle invasive bladder carcinomas. These pathways contained twelve TFs in total. We used the expression of the TFs to predict presence or absence of CIS in a Leave-One-Out Cross Validation classification. We showed that TF expression levels in three pathways (FGF, p38 MAPK, and calcium signalling) or the expression of the twelve TFs together could be used to predict presence or absence of concomitant CIS. A cluster analysis based on expression of the twelve TFs separated the samples in two main clusters: one branch contained 11 of the 15 patients without concomitant CIS and with the majority of the genes being down regulated; the other branch contained 10 of 13 patients with concomitant CIS, and here genes were mostly up regulated. The expression in the CIS group was comparable to the expression of twenty-three patients suffering from muscle-invasive bladder carcinoma. Finally, we validated our results in an independent test set and found that prediction of CIS status was possible using TF expression of the p38 MAPK pathway. We conclude that it is possible to use pathway analysis for molecular classification of bladder tumors

  17. [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.

  18. Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for urothelial cell carcinoma of the urinary bladder 2017

    Directory of Open Access Journals (Sweden)

    Hulayel Alharbi

    2018-01-01

    Full Text Available This is an update to the previously published Saudi guidelines for the evaluation and medical/surgical management of patients diagnosed with urothelial cell carcinoma of the urinary bladder. It is categorized according to the stage of the disease using the tumor node metastasis staging system, 7th edition. The guidelines are presented with their accompanying supporting evidence level, which is based on comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors who were selected by the Saudi Oncology Society and Saudi Urological Association. Considerations to the local availability of drugs, technology, and expertise have been regarded. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health-care policymakers in the management of patients diagnosed with urothelial cell carcinoma of the urinary bladder.

  19. Late effects of radiation therapy for prostate carcinoma: The patient`s perspective of bladder, bowel and sexual morbidity

    Energy Technology Data Exchange (ETDEWEB)

    Franklin, C.I.V.; Parker, C.A.; Morton, K.M. [Queensland Radium Institute, Herston, QLD (Australia)

    1998-02-01

    The patients` perceptions of the late effects of radiation therapy for carcinoma of the prostate on bladder, bowel and sexual function were determined by using a self-administered questionnaire (included as an appendix) which was posted in June 1996 to patients who had been treated for carcinoma of the prostate between February 1993 and April 1994 at the Herston centre of the Queensland Radium Institute. The questions were based on the SOMA-LENT subjective scales. Moderate bladder morbidity was reported by 15% of patients, with 2% reporting major morbidity. Moderate bowel morbidity was reported by 19% of patients with 2% reporting major morbidity, the major symptoms being bowel urgency and mucus discharge. Sexual function was a problem, with 72% of patients reporting dissatisfaction with their current level of sexual activity. Copyright (1998) Blackwell Science Pty Ltd 12 refs., 5 tabs., 2 figs.

  20. Late effects of radiation therapy for prostate carcinoma: The patient's perspective of bladder, bowel and sexual morbidity

    International Nuclear Information System (INIS)

    Franklin, C.I.V.; Parker, C.A.; Morton, K.M.

    1998-01-01

    The patients' perceptions of the late effects of radiation therapy for carcinoma of the prostate on bladder, bowel and sexual function were determined by using a self-administered questionnaire (included as an appendix) which was posted in June 1996 to patients who had been treated for carcinoma of the prostate between February 1993 and April 1994 at the Herston centre of the Queensland Radium Institute. The questions were based on the SOMA-LENT subjective scales. Moderate bladder morbidity was reported by 15% of patients, with 2% reporting major morbidity. Moderate bowel morbidity was reported by 19% of patients with 2% reporting major morbidity, the major symptoms being bowel urgency and mucus discharge. Sexual function was a problem, with 72% of patients reporting dissatisfaction with their current level of sexual activity. Copyright (1998) Blackwell Science Pty Ltd

  1. Diagnostic and Prognostic Significance of Serum and Tissue Galectin 3 Expression in Patients with Carcinoma of the Bladder

    Science.gov (United States)

    Gendy, Hoda El; Madkour, Bothina; Abdelaty, Sara; Essawy, Fayza; Khattab, Dina; Hammam, Olfat; Nour, Hani H.

    2014-01-01

    Background Galectins are group of proteins found in the cytoplasm, nucleus, cell surface and extracellular matrix. Galectin 3 (Gal-3) displays pathological expression in a variety of processes such as tumorigenesis. Patients and Method 70 patients classified into the control group, cystitis group, transitional cell carcinoma group, and squamous cell carcinoma group were enrolled in this study which aimed to detect the serum level and the intensity of tissue expression of Gal-3. Results Both serum level and tissue expression of Gal-3 were statistically higher in bladder cancer patients compared to the other groups. Gal-3 level expression increased from low to high grade urothelial tumors, with a statistically significant increase of its level and expression between muscle invasive and non-muscle invasive Ta urothelial tumors. Conclusion The serum Gal-3 level is sensitive and specific for the diagnosis of bladder cancer. The prognostic significance of tissue expression is to be confirmed. PMID:26195948

  2. Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for urothelial cell carcinoma of the urinary bladder 2017.

    Science.gov (United States)

    Alharbi, Hulayel; Alkhateeb, Sultan; Murshid, Esam; Alotaibi, Mohammed; Abusamra, Ashraf; Rabah, Danny; Almansour, Mubarak; Alghamdi, Abdullah; Aljubran, Ali; Eltigani, Amin; Alkushi, Hussein; Ahmed, Imran; Alsharm, Abdullah; Bazarbashi, Shouki

    2018-01-01

    This is an update to the previously published Saudi guidelines for the evaluation and medical/surgical management of patients diagnosed with urothelial cell carcinoma of the urinary bladder. It is categorized according to the stage of the disease using the tumor node metastasis staging system, 7 th edition. The guidelines are presented with their accompanying supporting evidence level, which is based on comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors) who were selected by the Saudi Oncology Society and Saudi Urological Association. Considerations to the local availability of drugs, technology, and expertise have been regarded. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health-care policymakers in the management of patients diagnosed with urothelial cell carcinoma of the urinary bladder.

  3. 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

  4. Neoadjuvant intra-arterial chemotherapy with a combination of radiotherapy for the treatment of invasive bladder carcinoma

    International Nuclear Information System (INIS)

    Sumiyoshi, Yoshiteru; Uyama, Takeshi.

    1992-01-01

    Fifty patients with invasive bladder carcinoma were treated with neoadjuvant intra-arterial chemotherapy using doxorubicin or pirarubicin, and this was combined with low dose radiotherapy. All of 50 patients were evaluated for clinical and histological efficacy. Twenty-nine of 50 (58%) patients achieved a clinically complete remission (CR) and 17 of 50 (34%) achieved a clinically partial remission (PR). Twenty-eight of 50 (56%) achieved a histological CR and 13 of 50 (26%) achieved a histological PR. The patients who underwent bladder preservation operations after this treatment and were followed up for longer than 3 years were evaluated for long-term results. The 5-year survival for 35 patients in this group was 74.1%. The 5-year survival for patients with a clinical CR was 93.3%, and for patients with a clinical PR it was 45.3%. The survival for patients with a histological CR was 93.3%, and for patients with a histological PR, it was 85.7%. This study suggests that neoadjuvant intra-arterial chemotherapy plus radiotherapy is a useful regimen that could become the treatment of first choice for patients with invasive bladder carcinoma. Patients who achieved a histological CR or PR with this regimen, might be able to retain the function of their bladders. (author)

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Immunohistochemical positive stained p53 protein in bladder transitional cell carcinoma

    Directory of Open Access Journals (Sweden)

    Halimi Monireh

    2009-04-01

    Full Text Available Background: Molecular genetics and immunopathologic analysis of bladder cancer have shown some abnormalities in a number of genes and proteins that have been implicated in the development and progression of such tumors, mainly in the p53 pathway. Aims: To investigate the rate of positively stained p53 protein in patients with urothelial papillary carcinoma of the bladder (UCB by immunohistochemistry and its relationship with tumor grade, gender and age of the patients. Settings and Design: During the present cross-sectional study, 100 paraffin-embedded specimens of UCB, which were provided from biopsies of the bladder by transurethral access, were immunohistochemically stained and studied for p53 protein from May 2006 to May 2007 in our referral center pathology laboratory. Materials and Methods: First, 4 µm slices of paraffin sections were provided and then stained by the avidin-biotin peroxidase method. The rate of positively stained p53 protein (defined as positive nuclear staining in over 10% of the cells was assessed. This rate was also estimated and compared between grades, genders and age-related groups (< 70 years, ≥70 years. Statistical Analysis: The χ2 , Fisher′s exact test and Mann-Whitney U test were used for comparing. Results: The overall rate of positively stained specimens was 11% for nuclear p53 protein. This rate was significantly higher in females (10/29 vs. 1/71; P < 0.001; odds ratio [OR]: 0.23; 95% confidence interval [CI]: 4.43-306.08, patients with 70 or older than 70 years (8/42 vs. 3/58; P = 0.04; OR: 0.55; 95% CI: 1.07-17.39 and in high-grade tumors (10/58 vs. 1/42; P = 0.02; OR: 0.59; 95% CI: 0.01-0.95. Conclusions: The rate of positively stained p53 protein for UCB was lower in our population. This rate was also higher in females, patients with 70 or older than 70 years and high grade of UCB.

  7. Proteomic analysis of human oral verrucous carcinoma

    African Journals Online (AJOL)

    Jane

    2011-10-05

    Oct 5, 2011 ... This study is about proteomic analysis of oral verrucous carcinoma (OVC). The total proteins ..... receptor protein (recoverin) through autoimmunity ..... chromosome 8q21.1 and overexpressed in human prostate cancer. Cancer ...

  8. 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.

  9. Identification of key pathways and genes influencing prognosis in bladder urothelial carcinoma

    Directory of Open Access Journals (Sweden)

    Ning X

    2017-03-01

    Full Text Available Xin Ning, Yaoliang Deng Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, People’s Republic of China Background: Genomic profiling can be used to identify the predictive effect of genomic subsets for determining prognosis in bladder urothelial carcinoma (BUC after radical cystectomy. This study aimed to investigate potential gene and pathway markers associated with prognosis in BUC.Methods: A microarray dataset of BUC was obtained from The Cancer Genome Atlas database. Differentially expressed genes (DEGs were identified by DESeq of the R platform. Kaplan–Meier analysis was applied for prognostic markers. Key pathways and genes were identified using bioinformatics tools, such as gene set enrichment analysis, gene ontology, the Kyoto Encyclopedia of Genes and Genomes, gene multiple association network integration algorithm (GeneMANIA, Search Tool for the Retrieval of Interacting Genes/Proteins, and Molecular Complex Detection.Results: A comparative gene set enrichment analysis of tumor and adjacent normal tissues suggested BUC tumorigenesis resulted mainly from enrichment of cell cycle and DNA damage and repair-related biological processes and pathways, including TP53 and mitotic recombination. Two hundred and fifty-six genes were identified as potential prognosis-related DEGs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the potential prognosis-related DEGs were enriched in angiogenesis, including the cyclic adenosine monophosphate biosynthetic process, cyclic guanosine monophosphate-protein kinase G, mitogen-activated protein kinase, Rap1, and phosphoinositide-3-kinase-AKT signaling pathway. Nine hub genes, TAGLN, ACTA2, MYH11, CALD1, MYLK, GEM, PRELP, TPM2, and OGN, were identified from the intersection of protein–protein interaction and GeneMANIA networks. Module analysis of protein–protein interaction and GeneMANIA networks mainly showed

  10. Clinical Significance of ErbB Receptor Family in Urothelial Carcinoma of the Bladder: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yuh-Shyan Tsai

    2012-01-01

    Full Text Available The prognostic importance of examining ErbB receptor family expression in human bladder cancer remains uncertain. Using published evidence, we examined the clinical value and the updated results of clinical trials targeting ErbB receptor family members. Twenty-seven articles from 65 references related to ErbB receptor expression assessment in bladder cancer were reviewed. The estimates included the association significance, hazard ratios, and 95% confidence intervals (CIs from actuarial curves and survival analyses. A meta-analysis was done on those reports using univariate log-rank tests or a Cox-regression model. The methods of analysis and study subjects chosen varied widely among studies. The overall risks of disease progression for patients with EGFR or ErbB2 overexpression were 4.5 (95% CI: 2.5–8.4 and 1.1 (95% CI: 0.6–1.9, and the risks of mortality were 3.0 (95% CI: 1.6–5.9 and 1.1 (95% CI: 1.0–1.2, respectively. However, the significance of coexpression patterns of the ErbB receptor family remains controversial. None of six clinical trials yielded convincing results for blockading ErbB receptor signaling in urothelial carcinoma. The results of this analysis suggest that assessing co-expression patterns of the ErbB family may provide better prognostic information for bladder cancer patients.

  11. 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)

  12. 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.

  13. [Expression and clinical significance of 5hmC in bladder urothelial carcinoma].

    Science.gov (United States)

    Li, Jie; Xu, Yuqiao; Zhang, Zhiwen; Zhang, Ming; Zhang, Zhekai; Zhang, Feng; Li, Qing

    2016-02-01

    To investigate the expression of 5-hydroxymethylcytosine (5hmC) in bladder urothelial carcinoma (UC) and its clinical significance. The expression of 5hmC in 21 cases of UC tissues and pericarcinous urinary tract epithelium was detected by immunohistochemical staining. Then the expression of 5hmC in the surgical resection of UC tissues in 92 cases was also surveyed. Non parametric U Mann-Whitney test was used to analyze the correlation between 5hmC expression and clinical data. Single factor survival analysis was performed by Kaplan-Meier test. The expression of 5hmC in normal urinary tract epithelium and UC tissues was significantly different, but there was no significant difference in the expression of 5hmC between low and high grades of UC tissues as well as between different TNM grades. Kaplan-Meier single factor survival analysis showed that there was no significant correlation between the 5hmC expression level and the survival rate or the recurrence-free survival of UC patients. The expression level of 5hmC in UC tissues is significantly lower than that in pericarcinous urinary tract epithelium. There is no correlation between the 5hmC expression and the progression, prognosis and recurrence of UC.

  14. Overexpression of BLCAP induces S phase arrest and apoptosis independent of p53 and NF-kappa B in human tongue carcinoma - BLCAP overexpression induces S phase arrest and apoptosis

    NARCIS (Netherlands)

    Yao, Jun; Duan, Li; Fan, Mingwen; Yuan, Jianhuan; Wu, Xinxing

    Bladder cancer-associated protein gene (BLCAP) is a novel candidate tumor suppressor gene identified from the human bladder carcinoma. Our previous studies have shown that BLCAP overexpression could inhibit cell growth by inducing apoptosis in HeLa cells [Zuo Z, Zhao M, Liu J, Gao G, Wu X: Tumor

  15. 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

  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. Rhabdomyosarcoma of the urinary bladder in adults: predilection for alveolar morphology with anaplasia and significant morphologic overlap with small cell carcinoma.

    Science.gov (United States)

    Paner, Gladell P; McKenney, Jesse K; Epstein, Jonathan I; Amin, Mahul B

    2008-07-01

    Rhabdomyosarcoma (RMS) represents the most common malignant soft tissue tumor in children and adolescents with the urinary bladder representing a frequent site. Most of these urinary bladder tumors are embryonal RMS, predominantly the botryoid subtype. RMSs of the urinary bladder in adults are distinctively rare and the subject of only case reports. We report the clinicopathologic features of 5 bladder neoplasms with rhabdomyosarcomatous differentiation in adults and emphasize the differential diagnosis in the adult setting. The patients, 4 men and 1 woman, ranged in age from 23 to 85 years (mean 65.4 y). Gross hematuria was the most common initial symptom, although 2 patients had metastatic disease at presentation. Four cases were pure primary RMSs of the bladder and 1 case was a sarcomatoid urothelial carcinoma with RMS representing the extensive heterologous component. All 5 cases demonstrated a diffuse growth pattern (ie, non-nested), of which 4 cases had nuclear anaplasia (Wilms criteria without the atypical mitotic figure requirement); only 1 case (the sarcomatoid carcinoma) showed obvious rhabdomyoblastic differentiation (ie, strap cells). Three cases were of the alveolar subtype (1 admixed with embryonal histology) and 2 were RMS, not further classified. Microscopically, all tumors had a primitive undifferentiated morphology with cells containing scant cytoplasm, varying round to fusiform nuclei with even chromatin distribution, and frequent mitoses. The degree of morphologic overlap with small cell carcinoma of the bladder, a relatively more common round cell tumor in adults, was striking. The epithelial component of the sarcomatoid carcinoma was high-grade invasive urothelial carcinoma with glandular differentiation. No other case had previous history of bladder cancer or concurrent carcinoma in situ or invasive urothelial carcinoma. All tumors showed immunohistochemical expression for desmin, myogenin, and/or MyoD1. Synaptophysin was performed in 4 cases

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

    Science.gov (United States)

    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.

  19. Can Bcl-XL expression predict the radio sensitivity of Bilharzial-related squamous bladder carcinoma? a prospective comparative study

    Directory of Open Access Journals (Sweden)

    Kamel Nermen A

    2011-01-01

    Full Text Available Abstract Background Local pelvic recurrence after radical cystectomy for muscle invasive bilharzial related squamous cell carcinoma accounts for 75% of treatment failures even in organ confined tumors. Despite the proven value of lymphadenectomy, up to 60% of patients undergoing cystectomy do not have it. These factors are in favor of adjuvant radiotherapy reevaluation. objectives: to evaluate the effect of adjuvant radiotherapy on disease free survival in muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder and to test the predictability of radio-sensitivity using the anti apoptotic protein Bcl-XL. Methods The study prospectively included 71 patients, (47 males, 24 females with muscle invasive bilharzial related squamous cell carcinoma of the bladder (Stage pT2a-T3N0-N3M0 who underwent radical cystectomy in Assiut university hospitals between January 2005 and December 2006. Thirty eight patients received adjuvant radiotherapy to the pelvis in the dose of 50Gy/25 fractions/5 weeks (Group 1, while 33 patients did not receive adjuvant radiotherapy (group 2. Immunohistochemical characterization for bcl-xL expression was done. Follow up was done every 3 months for 12 to 36 months with a mean of 16 ± 10 months. All data were analyzed using SPSS version 16. Three years cumulative disease free survival was calculated and adjusted to Bcl-XL expression and side effects of the treatment were recorded. Results The disease free cumulative survival was 48% for group 1 and 29% for group 2 (log rank p value 0.03. The multivariate predictors of tumor recurrence were the positive Bcl-XL expression (odd ratio 41.1, 95% CI 8.4 - 102.3, p Conclusions Adjuvant radiotherapy for muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder has potential effectiveness and minor side effects. Moreover, Bcl-XL expression is a valuable tool for predicting those who might not respond to this adjuvant treatment.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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...

  5. Incidental Diagnosis of Carcinoma of the Bladder Due to Uptake of {sup 99m}Tc-MDP

    Energy Technology Data Exchange (ETDEWEB)

    Damle, Nishikant A; Pandey, Dinesh Chand; Gautam, Awadhesh Kumar; Subbarao, Kiran; Singh, Prabhjot [All India Institute of Medical Sciences, New Delhi (India); Mishra, Rohini; Das, Nitendra Lal; Pandey, Dinesh Chand; Gautam, Awadhesh Kumar [B. L. Kapur Memorial Hospital, New Delhi (India)

    2012-06-15

    A bone scan was per-formed using 740 MBq (29 mCi) {sup 99}mTc-MDP. Whole-body planar images were acquired 3 h after injection (Fig. 1). Soft tissue uptake of {sup 99}mTc-MDP is described in various benign and malignant conditions. It is known to accumulate in adenocarcinoma of lung, primary breast cancer, and colonic carcinoma among others. The postulated causes of {sup 99}mTc-MDP uptake in extraosseous neoplasms are numerous and include tumor vascularity, inflammation, local pH factors, altered calcium metabolism, hormonal influences and cell wall damage. Our case shows that TCC of the bladder was incidentally diagnosed due to MDP uptake in multiple bladder polyps detected on a bone scan done for low backache in an 80-year-old man.

  6. Use of Artificial Intelligence and Machine Learning Algorithms with Gene Expression Profiling to Predict Recurrent Nonmuscle Invasive Urothelial Carcinoma of the Bladder.

    Science.gov (United States)

    Bartsch, Georg; Mitra, Anirban P; Mitra, Sheetal A; Almal, Arpit A; Steven, Kenneth E; Skinner, Donald G; Fry, David W; Lenehan, Peter F; Worzel, William P; Cote, Richard J

    2016-02-01

    Due to the high recurrence risk of nonmuscle invasive urothelial carcinoma it is crucial to distinguish patients at high risk from those with indolent disease. In this study we used a machine learning algorithm to identify the genes in patients with nonmuscle invasive urothelial carcinoma at initial presentation that were most predictive of recurrence. We used the genes in a molecular signature to predict recurrence risk within 5 years after transurethral resection of bladder tumor. Whole genome profiling was performed on 112 frozen nonmuscle invasive urothelial carcinoma specimens obtained at first presentation on Human WG-6 BeadChips (Illumina®). A genetic programming algorithm was applied to evolve classifier mathematical models for outcome prediction. Cross-validation based resampling and gene use frequencies were used to identify the most prognostic genes, which were combined into rules used in a voting algorithm to predict the sample target class. Key genes were validated by quantitative polymerase chain reaction. The classifier set included 21 genes that predicted recurrence. Quantitative polymerase chain reaction was done for these genes in a subset of 100 patients. A 5-gene combined rule incorporating a voting algorithm yielded 77% sensitivity and 85% specificity to predict recurrence in the training set, and 69% and 62%, respectively, in the test set. A singular 3-gene rule was constructed that predicted recurrence with 80% sensitivity and 90% specificity in the training set, and 71% and 67%, respectively, in the test set. Using primary nonmuscle invasive urothelial carcinoma from initial occurrences genetic programming identified transcripts in reproducible fashion, which were predictive of recurrence. These findings could potentially impact nonmuscle invasive urothelial carcinoma management. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  7. Molecular Characterization of Urothelial Carcinoma of the Bladder and Upper Urinary Tract

    Directory of Open Access Journals (Sweden)

    Ji Yun Lee

    2018-02-01

    Full Text Available PURPOSE: A better understanding of the molecular basis of urothelial carcinoma (UC is needed to refine the clinical decision-making process. METHODS AND MATERIALS: We performed next-generation sequencing to investigate the mutational and transcriptional profiles of commonly mutated genes in UC using Ampliseq v2. Copy number variations (CNVs were detected with nCounter assay. Genetic alterations between upper tract UC (UTUC and urinary bladder UC (UBUC were compared. RESULTS: Tumor samples from 31 UTUC and 61 UBUC patients were included in analysis. The two groups showed similar clinicopathologic features including tumor grade and stage. Median survival was longer in UTUC than UBUC patients, though this was statistically nonsignificant (59 vs 41 months, P = .137. In total, we found 982 genetic alterations from 92 samples: single nucleotide variants were the most common type of somatic mutation (479/508, 94.3%. Frequently detected somatic mutations included TP53 (68.5%, KDR (41.3%, and PIK3CA (17.4%. Notably, RB1 mutations were the only mutations significantly different between the UBUC and UTUC groups (19.7% vs. 0%, P = .020. The most common types of CNVs included amplifications (56/62, 90.3%: 17.7% of patients identified amplifications in NOTCH1. We also identified five translocations in the entire study population, including one case with FGFR3-TACC3 (Chr4 fusion. CONCLUSION: Within a small study population, we identified similar genetic alterations in both UTUC and UBUC patients, indicating a basis for similar management strategies.

  8. Activated platelet-derived growth factor β receptor and Ras-mitogen-activated protein kinase pathway in natural bovine urinary bladder carcinomas.

    Science.gov (United States)

    Corteggio, Annunziata; Di Geronimo, Ornella; Roperto, Sante; Roperto, Franco; Borzacchiello, Giuseppe

    2012-03-01

    Bovine papillomavirus types 1 or 2 (BPV-1/2) are involved in the aetiopathogenesis of bovine urinary bladder cancer. BPV-1/2 E5 activates the platelet-derived growth factor β receptor (PDGFβR). The aim of this study was to analyse the Ras/mitogen-activated protein kinase (MAPK) pathway in relation to activation of PDGFβR in natural bovine urinary bladder carcinomas. Co-immunoprecipitation and Western blot analysis demonstrated that recruitment of growth factor receptor bound protein 2 (GRB-2) and Sos-1 to the activated PDGFβR was increased in carcinomas compared to normal tissues. Higher grade bovine urinary bladder carcinomas were associated with activation of Ras, but not with activation of downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (Mek 1/2) or extracellular signal-regulated kinase (Erk 1/2). Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. 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.

  10. 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

  11. MDM2 SNP309 promoter polymorphism and p53 mutations in urinary bladder carcinoma stage T1

    Directory of Open Access Journals (Sweden)

    Olsson Hans

    2013-01-01

    Full Text Available Abstract Background Urinary bladder carcinoma stage T1 is an unpredictable disease that in some cases has a good prognosis with only local or no recurrence, but in others can appear as a more aggressive tumor with progression to more advanced stages. The aim here was to investigate stage T1 tumors regarding MDM2 promoter SNP309 polymorphism, mutations in the p53 gene, and expression of p53 and p16 measured by immunohistochemistry, and subsequently relate these changes to tumor recurrence and progression. We examined a cohort of patients with primary stage T1 urothelial carcinoma of the bladder and their tumors. Methods After re-evaluation of the original slides and exclusions, the study population comprised 141 patients, all with primary stage T1 urothelial carcinoma of the bladder. The hospital records were screened for clinical parameters and information concerning presence of histologically proven recurrence and progression. The paraffin-embedded tumor material was evaluated by immunohistochemistry. Any mutations found in the p53 gene were studied by single-strand conformation analysis and Sanger sequencing. The MDM2 SNP309 polymorphism was investigated by pyrosequencing. Multivariate analyses concerning association with prognosis were performed, and Kaplan-Meier analysis was conducted for a combination of changes and time to progression. Results Of the 141 patients, 82 had at least one MDM2 SNP309 G allele, and 53 had a mutation in the p53 gene, but neither of those anomalies was associated with a worse prognosis. A mutation in the p53 gene was associated with immunohistochemically visualized p53 protein expression at a cut-off value of 50%. In the group with p53 mutation Kaplan-Meier analysis showed higher rate of progression and shorter time to progression in patients with immunohistochemically abnormal p16 expression compared to them with normal p16 expression (p = 0.038. Conclusions MDM2 SNP309 promoter polymorphism and mutations in

  12. 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...

  13. 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....

  14. Intravesical markers for delineation of target volume during external focal irradiation of bladder carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Hulshof, Maarten C.C.M. [Department of Radiation Oncology, University of Amsterdam (Netherlands)]. E-mail: m.c.hulshof@amc.uva.nl; Andel, George van [Department of Urology, Onze Lieve Vrouwe Gasthuis, Amsterdam (Netherlands); Bel, Arjen [Department of Radiation Oncology, University of Amsterdam (Netherlands); Gangel, Pieter [Department of Radiation Oncology, University of Amsterdam (Netherlands); Kamer, Jeroen B. van de [Department of Radiation Oncology, University of Amsterdam (Netherlands)

    2007-07-15

    A clip forceps was developed which can insert markers at the border of a bladder tumour through a rigid cystoscope. This technique proved to be simple and safe and is of help for delineation of the target volume during CT simulation for focal boost irradiation of bladder cancer.

  15. Intravesical markers for delineation of target volume during external focal irradiation of bladder carcinomas

    International Nuclear Information System (INIS)

    Hulshof, Maarten C.C.M.; Andel, George van; Bel, Arjen; Gangel, Pieter; Kamer, Jeroen B. van de

    2007-01-01

    A clip forceps was developed which can insert markers at the border of a bladder tumour through a rigid cystoscope. This technique proved to be simple and safe and is of help for delineation of the target volume during CT simulation for focal boost irradiation of bladder cancer

  16. Intravesical markers for delineation of target volume during external focal irradiation of bladder carcinomas.

    Science.gov (United States)

    Hulshof, Maarten C C M; van Andel, George; Bel, Arjen; Gangel, Pieter; van de Kamer, Jeroen B

    2007-07-01

    A clip forceps was developed which can insert markers at the border of a bladder tumour through a rigid cystoscope. This technique proved to be simple and safe and is of help for delineation of the target volume during CT simulation for focal boost irradiation of bladder cancer.

  17. 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.

  18. Laparoscopic bilateral nephroureterectomy and bladder cuff excision for native renal pelvic and ureteral transitional cell carcinoma after renal transplantation.

    Directory of Open Access Journals (Sweden)

    Chen C

    2003-01-01

    Full Text Available A 37-years-old female who was suffering from end-stage renal disease for about 6 years received allograft renal transplantation 4 years ago. She has been receiving 50mg of Cyclosporin A orally daily for immuno-suppression since then. Gross haematuria was noted and computerised tomography showed native left renal pelvic and ureteral multi-focal transitional cell carcinoma with severe hydronephrosis. Laparoscopic bilateral nephroureterectomy and bladder cuff excision were performed. In the past, history of previous operation was considered a relative contraindication for laparoscopic surgery. To our knowledge, we present the first case of laparoscopic treatment for native renal pelvic and ureteral transitional cell carcinoma after renal allograft transplantation without a hand-assisted device. This case shows the feasibility of laparoscopic bilateral nephroureterectomy in patients with transplanted kidneys.

  19. [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.

  20. Clinico-pathological pattern, classification and staging of urinary bladder carcinomas - a five years experience at a tertiary care hospital in central punjab

    International Nuclear Information System (INIS)

    Naeem, A.

    2015-01-01

    In Pakistan, urinary bladder carcinoma is the 8th commonest malignancy while being the fourth commonest cancer in men. The relative occurrence of a particular histological type of bladder carcinoma depends on the clinical setting. Both grade and stage of these cancers are highly correlated with recurrence, progression and patient survival rates. Methods: This cross-sectional study comprised of 122 patients with newly diagnosed operable primary bladder carcinomas who underwent cystoscopy associated transurethral resection of bladder tumour at the Urology Department of Punjab Employees Social Security Hospital, Lahore. All participants completed a detailed questionnaire and underwent an in-depth interview to obtain data. The surgical specimens were referred to the Pathology department. Gross observations of the tumour recorded. Result: A total of 114 cases, classified according to WHO/ISUP criteria, low-grade papillary lesions, comprising Papillary Urothelial Neoplasm of Low Malignant Potential (PUNLMP) and Papillary Low Grade carcinomas, accounted for 43% of tumours. Male to female ratio being 5.3:1 (74%). Lateral walls were involved in 44%, posterior wall in 25.3%, trigone in 10.7%, bladder neck in 7.2%, dome in 5.8%, ureteric orifice in 4.13%, anterior wall in 2% and left ureter in 0.87% cases. Tumour staging revealed an overall 11.5% of tumours with stage Ta and 31.5% with stage T3-4. About 29% tumours were non invasive. About n=13 of low-grade carcinomas and n=68 of high-grade carcinomas were invasive. For tumours classified by WHO/ISUP criteria, the percentage of women was larger for PUNLMP than for the other categories of urothelial tumours (p-value 0.006); no statistically significant difference was found by age or gender with respect to tumour stage (p-value 0.138 and 0.452). Conclusion: Transitional Cell Carcinoma (TCC) is the commonest among middle aged men. (author)

  1. 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.

  2. 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

  3. Clinical usefulness of CEA, CA19-9, and CYFRA 21-1 as tumor markers for urothelial bladder carcinoma.

    Science.gov (United States)

    Washino, Satoshi; Hirai, Masaru; Matsuzaki, Atsushi; Kobayashi, Yutaka

    2011-01-01

    To evaluate the usefulness of measuring serum CEA, CA19-9, and CYFRA 21-1 levels for the diagnosis and monitoring of bladder cancer. Serum levels of CEA, CA19-9, and CYFRA 21-1 were measured in 85 patients with bladder cancer. The absolute level of each marker and the positive rate were compared with the clinical stage and histological grade of the tumor. Changes of the markers were assessed in patients with or without disease progression, and the correlations between survival and positivity/negativity of these markers were also evaluated. A higher serum level of CYFRA 21-1 was significantly correlated with higher tumor stage (p CEA and CA19-9 levels did not differ significantly among each stage and grade. The CYFRA 21-1 level increased significantly along with disease progression (from 7.33 ± 13.3 to 55.9 ± 127 ng/ml, p marker of advanced- and high-grade urothelial carcinoma of the bladder. It is useful for monitoring this disease and for predicting the prognosis. In contrast, the clinical usefulness of CEA and CA19-9 as tumor markers was not demonstrated. Copyright © 2011 S. Karger AG, Basel.

  4. Using Copy Number Alterations to Identify New Therapeutic Targets for Bladder Carcinoma

    Directory of Open Access Journals (Sweden)

    Donatella Conconi

    2016-02-01

    Full Text Available Bladder cancer represents the ninth most widespread malignancy throughout the world. It is characterized by the presence of two different clinical and prognostic subtypes: non-muscle-invasive bladder cancers (NMIBCs and muscle-invasive bladder cancers (MIBCs. MIBCs have a poor outcome with a common progression to metastasis. Despite improvements in knowledge, treatment has not advanced significantly in recent years, with the absence of new therapeutic targets. Because of the limitations of current therapeutic options, the greater challenge will be to identify biomarkers for clinical application. For this reason, we compared our array comparative genomic hybridization (array-CGH results with those reported in literature for invasive bladder tumors and, in particular, we focused on the evaluation of copy number alterations (CNAs present in biopsies and retained in the corresponding cancer stem cell (CSC subpopulations that should be the main target of therapy. According to our data, CCNE1, MYC, MDM2 and PPARG genes could be interesting therapeutic targets for bladder CSC subpopulations. Surprisingly, HER2 copy number gains are not retained in bladder CSCs, making the gene-targeted therapy less interesting than the others. These results provide precious advice for further study on bladder therapy; however, the clinical importance of these results should be explored.

  5. Clinicopathological spectrum of urothelial carcinoma of the urinary bladder - a study of 541 cases at afip pakistan

    International Nuclear Information System (INIS)

    Ahmed, R.; Hashmi, S.N.; Muhammad, I.

    2015-01-01

    Objective: To analyze the clinicopathological spectrum of urothelial carcinoma of urinary bladder. Study Design: Descriptive case series. Place and Duration of Study: Armed Forces Institute of Pathology (AFIP), from 1st January 2012 to 31st October 2013. Patients and methods: All cases of urothelial carcinoma were retrieved from AFIP tumour registry. Age, gender, histological type, grade and variant of tumour was noted. The data was analyzed by using computer software program SPSS version 19. Descriptive statistics and frequencies were calculated for age, gender, histological type, grade and variants. Results: A total of 541 cases of urothelial carcinoma were included in the study. The age at presentation ranged from 22 to 94 years with median age of 63.56 ± 12 years. A number (61%) of the cases were from 6th to 8th decade of life. The gender distribution showed 92.8% of patients (n=502) were males and 7.2 % (n=39) were females with male to female ratio of 12.9: 1. The most common histological type was papillary urothelial carcinoma; present in 493 cases (91.1%) followed by nonpapillary urothelial carcinoma; 48 cases (8.9%). Among papillary urothelial carcinomas, 302 cases (61.3%) were high grade and 191 cases (38.7%) were low grade. Among nonpapillary urothelial carcinomas, all were high grade and variant histology was observed in all cases. The variants included squamoid differentiation which was present in 27 cases (56.3%), nested variant in 8 cases (16.7%). The sarcomatoid, undifferentiated and clear cell variants in 3 cases (6.3%) each, micropapillary variant in 2 cases (4.2%), lymphoepithelial-like and plasmacytoid variant in 1 case (2.1%) each. Conclusion: Urothelial carcinoma is more common in males. Most of the tumours are papillary urothelial carcinomas. Most of them are high grade and pure urothelial carcinomas. A number of histologic variants are also recognized. Among them, squamoid differentiation is the most common variant histology. (author)

  6. [Synergism inhibition of curcumin combined with cisplatin on T24 bladder carcinoma cells and its related mechanism].

    Science.gov (United States)

    Zhang, Shao-nan; Yong, Qun; Wu, Xin-li; Liu, Xiao-ping

    2014-11-01

    To investigate the synergism inhibition of curcumin combined with cisplatin on T24 bladder carcinoma cells and the down-regulating effect of curcumin on the Keapl-Nrf2 pathway, a well recognized anti-drug pathway in almost drugged tumor cells. T24 cells were cultured and treated with increasing concentrations of curcumin(5 ,10 and 20 µmol/mL) combined with cisplatin(30 µg/mL) for 24 hours. The inhibitory effects on T24 cells were tested with MTI colorimetric assay. Nuclear Nrf2 and Keapl , cytoplasmic Keapl and two typical phase II enzymes (GSTP1 and NQOl) were checked with Western blotting. The proliferation of T24 cells was significantly inhibited by different concentrations of curcumin combined with cisplatin. After the treatment with different concentrations of curcumin, Nuclear Nrf2 was decreased but Keapl was increased, and GSTP1 and NQO1 were decreased. Synergism inhibition of curcumin combined with cisplatin on T24 bladder carcinoma cells is observed in this research. The Keapl-Nrf2 pathway in T24 cells is down-regulated by curcumin. The expression of typical phase I enzymes (GSTP1 and NQO1) mediated by Nrf2 are decreased by curcumin. The sensitivity of tumor cells to chemotherapeutic drugs is then enhanced. These may be the mechanism of synergism effect of curcumin combined with cisplatin.

  7. Recurrent bladder carcinoma: clinical and prognostic role of 18 F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Alongi, Pierpaolo [San Raffaele G. Giglio Institute, Department of Radiological Sciences, Nuclear Medicine Unit, Cefalu (Italy); Caobelli, Federico [Basel University Hospital, Department of Nuclear Medicine, Basel (Switzerland); Gentile, Roberta; Baldari, Sergio [University of Messina, Nuclear Medicine Unit, Department of Biomedical Sciences and Morphological and Functional Images, Messina (Italy); Stefano, Alessandro; Russo, Giorgio; Gilardi, Maria Carla [IBFM-CNR, Cefalu (Italy); Albano, Domenico [Universita degli Studi di Palermo, DIBIMEF - Sezione di Scienze Radiologiche, Palermo (Italy); Midiri, Massimo [San Raffaele G. Giglio Institute, Department of Radiological Sciences, Nuclear Medicine Unit, Cefalu (Italy); Universita degli Studi di Palermo, DIBIMEF - Sezione di Scienze Radiologiche, Palermo (Italy)

    2017-02-15

    A small number of studies evaluated the detection rate of lesions from bladder carcinoma (BC) of 18 F-FDG PET/CT in the restaging process. However, the prognostic role of FDG PET/CT still remains unclear. The aim of the present study was to evaluate the accuracy, the effect upon treatment decision, and the prognostic value of FDG PET/CT in patients with suspected recurrent BC. Forty-one patients affected by BC underwent FDG PET/CT for restaging purpose. The diagnostic accuracy of visually interpreted FDG PET/CT was assessed compared to histology (n = 8), other diagnostic imaging modalities (contrast-enhanced CT in 38/41 patients and MRI in 15/41) and clinical follow-up (n = 41). Semiquantitative PET values (SUVmax, SUVmean, SUL, MTV, TLG) were calculated using a graph-based method. Progression-free survival (PFS) and overall survival (OS) were assessed by using Kaplan-Meier curves. The risk of progression (hazard ratio, HR) was computed by Cox regression analysis by considering all the available variables. PET was considered positive in 21 of 41 patients. Of these, recurrent BC was confirmed in 20 (95 %). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG PET/CT were 87 %, 94 %, 95 %, 85 %, 90 %. AUC was 0.9 (95 %IC 0.8-1). Bayesian positive and negative likelihood ratios were 14.5 and 0.13, respectively. FDG PET/CT findings modified the therapeutic approach in 16 patients (modified therapy in 10 PET-positive patients, watch-and-wait in six PET-negative patients). PFS was significantly longer in patients with negative scan vs. those with pathological findings (85 % vs. 24 %, p < 0.05; HR = 12.4; p = 0.001). Moreover, an unremarkable study was associated with a longer OS (88 % vs. 47 % after 2 years and 87 % vs. 25 % after 3 years, respectively, p < 0.05). Standardized uptake value (SUV)max > 6 and total lesion glycolysis (TLG) > 8.5 were recognized as the most accurate thresholds to predict PFS (2-year PFS 62 % for

  8. Progression of urothelial carcinoma in situ of the urinary bladder: a switch from luminal to basal phenotype and related therapeutic implications.

    Science.gov (United States)

    Barth, Isabella; Schneider, Ursula; Grimm, Tobias; Karl, Alexander; Horst, David; Gaisa, Nadine T; Knüchel, Ruth; Garczyk, Stefan

    2018-05-01

    The stratification of bladder cancer into luminal and basal tumors has recently been introduced as a novel prognostic system in patient cohorts of muscle-invasive bladder cancer or high-grade papillary carcinomas. Using a representative immunohistochemistry panel, we analyzed luminal and basal marker expression in a large case series (n = 156) of urothelial carcinoma in situ (CIS), a precancerous lesion that frequently progresses to muscle-invasive disease. The majority of CIS cases was characterized by a positivity for luminal markers (aberrant cytokeratin (CK) 20 85% (132/156), GATA3 median Remmele score (score of staining intensity (0-3) multiplied with percentage of positive cells (0-4)): 12, estrogen receptor (ER) β Remmele score > 2: 88% (138/156), human epidermal growth factor receptor 2 (Her2) Dako score 3+ 32% (50/156), Her2 Dako score 2+ 33% (51/156)), and marginal expression of basal markers (CK5/6+ 2% (3/156), CK14+ 1% (2/156)). To further investigate phenotypic stability during disease progression, we compared 48 pairs of CIS and invasive tumors from the same biopsy. A highly significant loss of luminal marker expression (p < 0.001) was observed in the course of progression whereas an increase of basal marker expression (p < 0.01) was noted in the invasive compartment. Importantly, 91% of CIS cases demonstrated a positivity for at least one of the two predictive markers Her2 and ERβ, indicating that the analysis of Her2 and ERβ may help to identify CIS-patient subgroups prone to more efficient targeted treatment strategies. Larger prospective and biomarker-embedded clinical trials are needed to confirm and validate our preliminary findings.

  9. Identification of Apo-A1 as a biomarker for early diagnosis of bladder transitional cell carcinoma

    Directory of Open Access Journals (Sweden)

    Wang Shixin

    2011-04-01

    Full Text Available Abstract Background Bladder transitional cell carcinoma (BTCC is the fourth most frequent neoplasia in men, clinically characterized by high recurrent rates and poor prognosis. Availability of urinary tumor biomarkers represents a convenient alternative for early detection and disease surveillance because of its direct contact with the tumor and sample accessibility. Results We tested urine samples from healthy volunteers and patients with low malignant or aggressive BTCC to identify potential biomarkers for early detection of BTCC by two-dimensional electrophoresis (2-DE coupled with mass spectrometry (MS and bioinformatics analysis. We observed increased expression of five proteins, including fibrinogen (Fb, lactate dehydrogenase B (LDHB, apolipoprotein-A1 (Apo-A1, clusterin (CLU and haptoglobin (Hp, which were increased in urine samples of patients with low malignant or aggressive bladder cancer. Further analysis of urine samples of aggressive BTCC showed significant increase in Apo-A1 expression compared to low malignant BTCC. Apo-A1 level was measured quantitatively using enzyme-linked immunosorbent assay (ELISA and was suggested to provide diagnostic utility to distinguish patients with bladder cancer from controls at 18.22 ng/ml, and distinguish patients with low malignant BTCC from patients with aggressive BTCC in two-tie grading system at 29.86 ng/ml respectively. Further validation assay showed that Apo-A1 could be used as a biomarker to diagnosis BTCC with a sensitivity and specificity of 91.6% and 85.7% respectively, and classify BTCC in two-tie grading system with a sensitivity and specificity of 83.7% and 89.7% respectively. Conclusion Taken together, our findings suggest Apo-A1 could be a potential biomarker related with early diagnosis and classification in two-tie grading system for bladder cancer.

  10. 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.

  11. Paeoniflorin inhibits the growth of bladder carcinoma via deactivation of STAT3

    Directory of Open Access Journals (Sweden)

    Yang Jianhui

    2018-06-01

    Full Text Available Bladder cancer (BCa is one of the most common urinary cancers. The present study aims to investigate whether Paeoniflorin (Pae can exert inhibitory effects on BCa. The results showed that Pae inhibited proliferation of human BCa cell lines in a concentration- and time-dependent manner. Pae and cisplatin (Cis synergistically inhibited the growth of tumours in RT4-bearing mice. Pae treatment neutralized the body loss induced by Cis. Moreover, Pae induced apoptosis in RT4 cells and increased the activities of caspase3, caspase8 and caspase9. Western blotting and immunohistochemical analysis revealed that the phosphorylated signal transducer and activator of transcription-3 (p-STAT3 level were decreased in Pae-treated RT4 cells and Pae-treated tumour-bearing mice. Furthermore, STAT3 transcriptional target B-cell lymphoma-2 was decreased in Pae-treated RT4 cells. Interestingly, Pae prevented translocation of STAT3 to the nucleus in RT4 cells. Collectively, Pae inhibits the growth of BCa, at least in part, via a STAT3 pathway.

  12. 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 ...

  13. Clinical features and outcomes of nontransitional cell carcinomas of the urinary bladder: Analysis of 125 cases

    Directory of Open Access Journals (Sweden)

    Burak Arslan

    2015-01-01

    Conclusion: Prognosis of urinary bladder tumors was directly related to histological type and stage of the tumor. CT or radiotherapy has limited response rates. Early radical cystectomy should be performed to improve prognosis.

  14. Superiority of fluorescent in situ hybridization over immunohistochemistry in detection of HER2 gene in carcinoma of the urinary bladder associated with and without schistosomiasis.

    Science.gov (United States)

    Hammam, Olfat; Wishahi, Mohamed; Hindawi, All; Mosaad, Maha; Akl, Maha; Khalil, Heba; Al Ganzoury, Hossam; Badawy, Mohamed; Elesaily, Khaled

    2014-12-01

    HER2 is an oncogene encoding a type 1 tyrosine kinase growth factor receptor and the role of HER2 in the development of numerous types of human cancer is still understood and correlates with clinical outcome, poor prognosis, it is a predictor factor for poor response to chemotherapy. HER2 overexpression is associated with reduced disease free and overall survival. Patients who have HER2 negative expression have a poor prognosis. The aim of the present study is to explore the accuracy of detection of expression of HER2 protein by two different techniques of immunohistochemistry (IHC) and gene amplification by fluorescent in situ hybridization (FISH). The two techniques were applied to sixty two patients that included different cell types of carcinoma of the bladder, benign bilharzial lesions and control. Characteristics of the 62 patients are: 10 chronic cystitis, 19 squamous cell carcinoma (SCC) with schistosomiasis, 33 urothelial carcinoma (UC) schistosomal and non-schistosomal, ten healthy individuals without schistosomiasis served as controls. Gene amplification of HER2 was done using FISH and protein expression of HER2 by IHC. The study was applied on archival data of formalin-fixed paraffin embedded tissues and patient clinical data and follow up for 5 years. Overexpression of HER2 protein was found in 30/52 (57.7%). Fourteen cases had score of 2+, and sixteen cases had score of 3+. Using FISH technique it showed more accurate detection of HER2 gene as those fourteen cases who had score of 2+ had been found to be 5 out of 14 were positive for gene over expression, the other sixteen who had score of 3+ all were positive for gene amplification. HER2 protein and gene was found to be significantly overexpressed in carcinoma of the bladder in both cell types SCC and UC with or without schistosomiasis compared to the benign lesions and control groups (P <0.01) by both techniques. There is significant increase in expression of HER2 protein and gene in SCC compared to

  15. Schistosomiasis-induced squamous cell bladder carcinoma in an HIV-infected patient

    DEFF Research Database (Denmark)

    Marbjerg, Lis Høy; Øvrehus, Anne Lindebo Holm; Johansen, Isik Somuncu

    2015-01-01

    haematuria for more than a year. Investigations revealed invasive S. haematobium-associated squamous cell bladder cancer. If her origin had been taken into account, the diagnosis might have been made earlier. Awareness of the disease prevalence among HIV co-infected patients from endemic areas and timely...... screening of such patients is important for the early diagnosis of schistosomiasis and related complications, such as S. haematobium-associated squamous cell bladder cancer....

  16. 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

  17. Association of PAX5 Expression with Clinical Outcome in Patients with TaT1 Transitional Cell Carcinoma of the Bladder

    Czech Academy of Sciences Publication Activity Database

    Babjuk, M.; Soukup, V.; Mareš, J.; Dušková, J.; Pecen, Ladislav; Pešl, M.; Pavlík, I.; Dvořáček, J.

    2006-01-01

    Roč. 67, č. 4 (2006), s. 756-761 ISSN 0090-4295 R&D Projects: GA MZd NR8095; GA MZd NR8934 Institutional research plan: CEZ:AV0Z10300504 Keywords : bladder carcinoma * PAX5 expression Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.130, year: 2006

  18. Voided urine versus bladder washing cytology for detection of urothelial carcinoma: which is better?

    Science.gov (United States)

    Keller, Anna Krarup; Jensen, Jørgen Bjerggaard

    2017-08-01

    Cytology is recommended as part of the follow-up of high-grade non-muscle-invasive bladder cancer (NMIBC). However, currently there are no solid guideline recommendations regarding the use of voided urine versus bladder washing for cytology as part of the diagnosis or follow-up of NMIBC. The aim of this study was to investigate whether the cytological outcome was equal regarding the two techniques. The authors reviewed all outpatient flexible cystoscopies carried out in their department in 2013. Patient records in the registry of pathology were examined and those with simultaneous urine and bladder washing cytology were included. Previous urothelial disease and positive histology within 3 months after the cystoscopy were registered. A total of 1458 patients had both voided urine and bladder washing cytology and were included in the study, of whom 643 (44%) had a history of urothelial disease. An equal outcome of urine and bladder washing cytology was found in 1447 patients (99.2%). For the remaining 11 patients, only four patients underwent further examinations based on cytology findings in addition to what had already been planned after cystoscopy. Of the included patients, 100 (6.9%) had a positive histological outcome within 3 months. In most patients, no relevant difference between voided urine and bladder washing cytology was observed. Therefore, if cytology is indicated, it is recommended to use the test that is most readily available locally. The additional gain in using both urine and bladder wash is minimal, and can therefore be discarded.

  19. 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

  20. 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.

  1. Performance of Urinary Markers for Detection of Upper Tract Urothelial Carcinoma: Is Upper Tract Urine More Accurate than Urine from the Bladder?

    Directory of Open Access Journals (Sweden)

    Simone Bier

    2018-01-01

    Full Text Available Objectives. To assess the performance of urine markers determined in urine samples from the bladder compared to samples collected from the upper urinary tract (UUT for diagnosis of UUT urothelial carcinoma (UC. Patients and Methods. The study comprised 758 urine samples either collected from the bladder (n=373 or UUT (n=385. All patients underwent urethrocystoscopy and UUT imaging or ureterorenoscopy. Cytology, fluorescence in situ hybridization (FISH, immunocytology (uCyt+, and nuclear matrix protein 22 (NMP22 were performed. Results. UUT UC was diagnosed in 59 patients (19.1% (UUT urine and 27 patients (7.2% (bladder-derived urine. For UUT-derived samples, sensitivities for cytology, FISH, NMP22, and uCyt+ were 74.6, 79.0, 100.0, and 100.0, while specificities were 66.6, 50.7, 5.9, and 66.7%, respectively. In bladder-derived samples, sensitivities were 59.3, 52.9, 62.5, and 50.0% whereas specificities were 82.9, 85.0, 31.3, and 69.8%. In UUT-derived samples, concomitant bladder cancer led to increased false-positive rates of cytology and FISH. Conclusions. Urine markers determined in urine collected from the UUT exhibit better sensitivity but lower specificity compared to markers determined in bladder-derived urine. Concomitant or recent diagnosis of UC of the bladder can further influence markers determined in UUT urine.

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

    Directory of Open Access Journals (Sweden)

    Lin JF

    2017-05-01

    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.Conclusion: Collectively, the study results indicated that cisplatin-induced autophagy is mediated by BECN1 in BC cells. Therefore, combinative treatment using cisplatin and autophagy inhibitors could potentially overcome cisplatin resistance related to autophagy induction. Keywords: autophagy inhibition, autophagy related genes, apoptosis, cisplatin resistance, human urinary bladder urothelial carcinoma, lentiviral-based shRNA

  3. Unusual presentation of high-grade neuroendocrine carcinoma of the Urinary bladder with small-cell and large-cell features

    Directory of Open Access Journals (Sweden)

    Vitor Fiorin de Vasconcellos

    2013-10-01

    Full Text Available High-grade neuroendocrine carcinoma of the urinary bladder comprehends small-cell and large-cell variants. It is a rare and aggressive neoplasm, mostly diagnosed in advanced stages. It is more frequently encountered among Caucasian men in the sixth decade of life. Urinary symptoms are the most common clinical presentation. Diagnosis is generally not troublesome once the lesions are easily detectable by imaging exams and cystoscopy. This neoplasia is associated with tobacco smoking, and is frequently associated with other carcinomatous components such as urothelial carcinoma, adenocarcinoma, and sarcomatoid carcinoma. The authors report a case of an apparently healthy female patient who presented cervical lymph node enlargement not accompanied by systemic symptoms. The supraclavicular lymph node biopsy revealed metastatic small cell carcinoma. The computed tomography scan showed a bladder wall nodular thickening, enlarged lymph nodes along the iliac, periaortic, mediastinal, cervical and supraclavicular chains, as well as an insufflating lytic bone lesion in the right iliac wing. The positron emission tomography-fluorodeoxyglucose (PET-FDG added to these findings, the presence of a paraesophageal lymph node, lymphadenomegaly in the gluteal region and a vertebral lytic lesion in T10. Resected specimen of the bladder tumor revealed a high-grade neuroendocrine carcinoma with small-cell and large-cell features.

  4. 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.

  5. 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...

  6. 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

  7. Effect of non-specific prophylaxis of thrombogenic complications on delayed results of combined treatment of bladder carcinoma

    International Nuclear Information System (INIS)

    Popov, A.I.

    1987-01-01

    Altogether 106 patients with bladder carcinoma (Stage T 3 N x M 0 ) after combined treatment were followed-up for 5 yrs. Nicotonic acid and aspirin at common doses were adminstrated to 51 patients (the 1st group) during pre- and postoperative radiation therapy. The other 55 patients (the 2nd group) did not receive these drugs. Relapses were noted in 33.3% of the patients of the 1st group and in 76.3% of the patients of the 2nd group. The 5-year survival in the 1st group was 72.5% and in the 2nd group 27.4%. The administration of nicotonic acid and aspirin to patients during pre- and postoperative γ-beam therapy was shown to raise the body antitumor resistance

  8. Risk estimation of multiple recurrence and progression of non muscle invasive bladder carcinoma using new mathematical models.

    Science.gov (United States)

    Luján, S; Santamaría, C; Pontones, J L; Ruiz-Cerdá, J L; Trassierra, M; Vera-Donoso, C D; Solsona, E; Jiménez-Cruz, F

    2014-12-01

    To apply new mathematical models according to Non Muscle Invasive Bladder Carcinoma (NMIBC) biological characteristics and enabling an accurate risk estimation of multiple recurrences and tumor progression. The classical Cox model is not valid for the assessment of this kind of events becausethe time betweenrecurrencesin the same patientmay be stronglycorrelated. These new models for risk estimation of recurrence/progression lead to individualized monitoring and treatment plan. 960 patients with primary NMIBC were enrolled. The median follow-up was 48.1 (3-160) months. Results obtained were validated in 240 patients from other center. Transurethral resection of the bladder (TURB) and random bladder biopsy were performed. Subsequently, adjuvant localized chemotherapy was performed. The variables analyzed were: number and tumor size, age, chemotherapy and histopathology. The endpoints were time to recurrence and time to progression. Cox model and its extensions were used as joint frailty model for multiple recurrence and progression. Model accuracy was calculated using Harrell's concordance index (c-index). 468 (48.8%) patients developed at least one tumor recurrence and tumor progression was reported in 52 (5.4%) patients. Variables for multiple-recurrence risk are: age, grade, number, size, treatment and the number of prior recurrences. All these together with age, stage and grade are the variables for progression risk. Concordance index was 0.64 and 0.85 for multiple recurrence and progression respectively. the high concordance reported besides to the validation process in external source, allow accurate multi-recurrence/progression risk estimation. As consequence, it is possible to schedule a follow-up and treatment individualized plan in new and recurrent NMCB cases. Copyright © 2014 AEU. Published by Elsevier Espana. All rights reserved.

  9. Pattern and Risk Factors of Urinary Bladder Neoplasms in ...

    African Journals Online (AJOL)

    It poses biologic and clinical challenges. ... Conclusion: There is significant relationship between urinary schistosomal infestation and the development of squamous cell carcinoma of the urinary bladder among Sudanese patients. Keywords: Urinary Bladder, Transitional Cell Carcinoma, Squamous Cell Carcinoma

  10. The Prognostic Role of NEDD9 and P38 Protein Expression Levels in Urinary Bladder Transitional Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ola A. Harb

    2017-01-01

    Full Text Available Background. The most common malignant tumor of the urinary bladder is transitional cell carcinoma (TCC. Neural precursor cell-expressed developmentally downregulated protein 9 (NEDD9 is found to be a cell adhesion mediator. P38 Mitogen-Activated Protein Kinase is a serine/threonine kinases member which can mediate carcinogenesis through intracellular signaling. Methods. To assess their prognostic role; NEDD9 and p38 protein were evaluated in sections from 50 paraffin blocks of TCC. Results. The high expressions of NEDD9 and p38 protein were significantly associated with grade, stage, distant metastasis (p<0.001, number of tumors, lymph node metastasis, and tumor size (p<0.001, 0.002; 0.018, <0.001; and 0.004, 0.007, respectively. High NEDD9 and p38 detection had a worse 3-year OS (p=0.041 and <0.001, respectively. By multivariate analysis the NEDD9 and p38 protein expression levels and various clinicopathological criteria including gender, grade, stage of the tumor, and regional lymph node involvement were independent prognostic parameters of TCC of the urinary bladder patients’ outcome. Conclusion. NEDD9 and p38 protein expressions were poor prognostic markers of TCC.

  11. Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of bladder carcinoma.

    Science.gov (United States)

    Kamat, Ashish M; Bellmunt, Joaquim; Galsky, Matthew D; Konety, Badrinath R; Lamm, Donald L; Langham, David; Lee, Cheryl T; Milowsky, Matthew I; O'Donnell, Michael A; O'Donnell, Peter H; Petrylak, Daniel P; Sharma, Padmanee; Skinner, Eila C; Sonpavde, Guru; Taylor, John A; Abraham, Prasanth; Rosenberg, Jonathan E

    2017-08-15

    The standard of care for most patients with non-muscle-invasive bladder cancer (NMIBC) is immunotherapy with intravesical Bacillus Calmette-Guérin (BCG), which activates the immune system to recognize and destroy malignant cells and has demonstrated durable clinical benefit. Urologic best-practice guidelines and consensus reports have been developed and strengthened based on data on the timing, dose, and duration of therapy from randomized clinical trials, as well as by critical evaluation of criteria for progression. However, these reports have not penetrated the community, and many patients do not receive appropriate therapy. Additionally, several immune checkpoint inhibitors have recently been approved for treatment of metastatic disease. The approval of immune checkpoint blockade for patients with platinum-resistant or -ineligible metastatic bladder cancer has led to considerations of expanded use for both advanced and, potentially, localized disease. To address these issues and others surrounding the appropriate use of immunotherapy for the treatment of bladder cancer, the Society for Immunotherapy of Cancer (SITC) convened a Task Force of experts, including physicians, patient advocates, and nurses, to address issues related to patient selection, toxicity management, clinical endpoints, as well as the combination and sequencing of therapies. Following the standard approach established by the Society for other cancers, a systematic literature review and analysis of data, combined with consensus voting was used to generate guidelines. Here, we provide a consensus statement for the use of immunotherapy in patients with bladder cancer, with plans to update these recommendations as the field progresses.

  12. Bladder squamous cell carcinomas express psoriasin and externalize it to the urine

    DEFF Research Database (Denmark)

    Celis, J E; Rasmussen, H H; Vorum, H

    1996-01-01

    were confined chiefly to the "squamous pearls." The presence of psoriasin in the urine of the 4 SCC patients was demonstrated by two-dimensional gel immunoblotting. Similar analysis of 43 urines from patients with bladder tumors other than SCC revealed 7 positives, some of which may reflect squamous...

  13. Survival after primary and deferred cystectomy for stage T1 transitional cell carcinoma of the bladder

    Directory of Open Access Journals (Sweden)

    Bedeir Ali-El-Dein

    2011-01-01

    Conclusions: Cancer-specific survival is statistically comparable for primary and deferred cystectomy in T1 bladder cancer, although there is a non-significant difference in favor of primary cystectomy. In the deferred cystectomy group, the number of TURBTs beyond three is associated with lower survival. Conservative treatment should be adopted for most cases in this category.

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

    International Nuclear Information System (INIS)

    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

  15. Selective bilateral internal iliac artery embolization for controlling refractory hematuria due to the metastatic squamous cell carcinoma of the urinary bladder: a case report

    Directory of Open Access Journals (Sweden)

    Gholamreza Mokhtari

    2016-09-01

    Full Text Available Bladder squamous cell carcinoma (SCC may lead to gross hematuria. However, the metastasis of head and neck cutaneous SCC to the urinary bladder has not been described in literature. Nowadays, noninvasive methods such as embolization, are considered as an appropriate choice for controlling life-threatening hematuria in patients with high operative risk. However, few reports exist on the effectiveness of this approach in managing the hematuria secondary to metastatic bladder SCC. Here we report a case of bladder SCC originating from the forehead cutaneous SCC. An 83-year-old man, a known case of forehead cutaneous SCC with distant metastasis, referred to our clinic with a chief complaint of hematuria. Pathology confirmed the diagnosis of metastatic urinary bladder SCC. Angiography and embolization were undertaken and resulted in complete alleviation of the symptoms. The recurrence of hematuria or embolization-related complications were not observed during 3-month follow-up. Selective embolization of the bilateral internal iliac artery is a safe and efficient procedure for controlling severe hematuria in patients with primary or metastatic bladder SCC.

  16. Suppression of urinary bladder urothelial carcinoma cell by the ethanol extract of pomegranate fruit through cell cycle arrest and apoptosis.

    Science.gov (United States)

    Lee, Song-Tay; Lu, Min-Hua; Chien, Lan-Hsiang; Wu, Ting-Feng; Huang, Li-Chien; Liao, Gwo-Ing

    2013-12-21

    Pomegranate possesses many medicinal properties such as antioxidant, anti-inflammation and antitumor. It has been extensively used as a folk medicine by many cultures. Pomegranate fruit has been shown to have the inhibitory efficacy against prostate cancer and lung cancer in vitro and in vivo. It can be exploited in chemoprevention and chemotherapy of prostate cancer. In this study we examined the anti-cancer efficacy of pomegranate fruit grown in Taiwan against urinary bladder urothelial carcinoma (UBUC) and its mechanism of action. Edible portion of Taiwanese pomegranate was extracted using ethanol and the anti-cancer effectiveness of ethanol extract was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry and western immunoblotting were exploited to uncover the molecular pathways underlying anti-UBUC activity of Taiwanese pomegranate ethanol extract. This study demonstrated that Taiwanese pomegranate fruit ethanol extract (PEE) could effectively restrict the proliferation of UBUC T24 and J82 cells. Cell cycle analyses indicated that the S phase arrest induced by PEE treatment might be caused by an increase in cyclin A protein level and a decrease in the expression of cyclin-dependent kinase 1. The results of western immunoblotting demonstrated that PEE treatment could not only evoke the activation of pro-caspase-3, -8,-9 but also increase Bax/Bcl-2 ratio in T24 cells. The above observations implicated that PEE administration might trigger the apoptosis in T24 cells through death receptor signaling and mitochondrial damage pathway. Besides we found that PEE exposure to T24 cells could provoke intensive activation of procaspase-12 and enhance the expressions of CHOP and Bip, endoplasmic reticulum (ER) stress marker, suggesting that ER stress might be the cardinal apoptotic mechanism of PEE-induced inhibition of bladder cancer cell. The analytical results of this study help to provide insight into the molecular mechanism

  17. The association between human papillomavirus and oropharyngeal squamous cell Carcinoma

    DEFF Research Database (Denmark)

    Walvik, Lena; Svensson, Amanda Björk; Friborg, Jeppe

    2016-01-01

    carcinoma using the Bradford Hill criteria. The strength of the association is supported by, detection of human papillomavirus infection and antibodies prior to oropharyngeal squamous cell carcinoma. This is furthermore reinforced by the absence of human papillomavirus DNA in healthy tonsils...... incidence in human papillomavirus positive oropharyngeal squamous cell carcinoma is associated with sexual behaviour. These associations have been repeatedly observed and are in accordance with our current knowledge. The time relation between cause and effect remains the main challenge, due to the lack...... of well-defined premalignant lesions. However, a causal relationship between human papillomavirus infection and oropharyngeal squamous cell carcinoma seems evident....

  18. Usefulness of the UBCTM (urinary bladder cancer) test compared to urinary cytology for transitional cell carcinoma of the bladder in patients with hematuria

    International Nuclear Information System (INIS)

    Gil, Myung Cheol; Kang, Do Young; Seong, Youl Koon

    2001-01-01

    Urinary cytology and cystoscopic exam are effective methods for diagnosis of transitional cell carcinoma (TCC). But the former shows drawbacks such as the need for a well-trained examiner, and wide imprecision related to the variability of microscopic exam; the latter is a invasive method. UBC TM test detects the epitope on specific cytokeratin fragments released from epithelium of bladder cancer by immunoradiometric assay. We compared UBC TM test with urinary cytology for diagnosis of TCC to evaluate the utility of UBC TM test. Eighty-four patients with hematuria were included in our study, UBC TM tests (IDL Biotech, Sweden) were assayed in mid-stream urine according to the ordinary assay protocol. Nineteen patients were confirmed as TCC by cystoscopic examination and underwent transurethral resection (Group A). Other patients had various benign urinary tract conditions (Group B). Samples were considered positive as the UBC TM concentration was greater than 12 μg/L. UBC TM levels were significantly different between group A (95.9 ±166.4 μg/L) and group B (19.2 ± 85.6 μg/L)(p TM test and 100% (65/65) in cytology. UBC TM test was significantly more sensitive in stage Ta, T 1 tumors (84.6 vs 38.5%, p TM test showed a tendency to be more sensitive as the grade was higher (83.3% in Grade 1, 90% in Grade II and 100% in Grade III). UBC TM test could be a useful method in distinguishing TCC from other benign genitourinary diseases. Moreover, UBC TM test could be an especially valuable marker for diagnosis of TCC in patients with early TCC of low grade TCC compared to urinary cytology. Therefore, mbined use of UBC TM test in association with cytology is helpful to overcome the limited sensitivity of cytology

  19. Adjuvant chemotherapy for superficial transitional cell bladder carcinoma : Long-term results of a European organization for research and treatment of cancer randomized trial comparing doxorubicin, ethoglucid and transurethral resection alone

    NARCIS (Netherlands)

    Kurth, K; Tunn, U; Ay, R; Schroder, FH; PavoneMacaluso, M; Debruyne, F; TenKate, F; DePauw, M; Sylvester, R; Essed, E; Caubergh, RV; Hoekstra, JW; deVoogt, HJ; Newling, DWW; deReijke, TM; Mensink, HJA; Groen, JM; Jakse, G; Leisinger, HJ; Richards, B; Adib, RA; Robinson, M; Denis, L; Bouffioux, C; Schulman, C; Carpentier, PJ

    Purpose: We compared the efficacy of transurethral resection alone or transurethral resection followed by bladder instillations of doxorubicin or ethoglucid for 1 year in patients with superficial bladder carcinoma, and followed them long term for the incidence of progression to muscle invasion.

  20. Expression levels of transcription factors c-Fos and c-Jun and transmembrane protein HAb18G/CD147 in urothelial carcinoma of the bladder.

    Science.gov (United States)

    Huhe, Muren; Liu, Shuangshuang; Zhang, Yang; Zhang, Zheng; Chen, Zhinan

    2017-05-01

    The aim of the present study was to investigate the prognostic significance of the expression of transcription factors, c-Fos, c-Jun and transmembrane protein CD147, in urothelial carcinoma of the bladder (UCB). The current study investigated the clinical significance of these factors in the development, progression and survival analysis of UCB. Immunohistochemistry was employed to analyze c‑Fos, c‑Jun and CD147 expression in 41 UCB cases and 34 non‑cancerous human bladder tissues. These results were scored in a semi‑quantitative manner based on the intensity and percentage of tumor cells that presented immunoreactivity. Protein levels of CD147, c‑Fos and c‑Jun expression were upregulated in 22 (53.7%), 10 (24.4%) and 9 (22.0%) UCB cases, respectively. High levels of c‑Jun correlated with the AJCC cancer staging manual (7th edition; P=0.038). Univariate analysis revealed that upregulated CD147 (P=0.038) or c‑Jun (P=0.008) was associated with poor overall survival (OS), respectively. Further analysis revealed that either CD147‑c‑Fos‑c‑Jun co‑expression (P=0.004), or CD147‑c‑Jun co‑expression (P=0.037) and c‑Fos‑c‑Jun co‑expression (PCD147, c‑Jun or c‑Fos were independent risk indicators for death in UCB patients. Increased expression of c‑Jun or CD147, as well as co‑expression of CD147‑c‑Jun, c‑Jun‑c‑Fos or CD147‑c‑Jun‑c‑Fos has prognostic significance for UCB patients. Therefore, high CD147 and c‑Jun expression may serve roles in tumor progression and may be diagnostic and therapeutic targets in UCB whether alone or in combination.

  1. Metastatic carcinoma of the urinary bladder in a 67-year-old female with underlying triple primary cancers

    Directory of Open Access Journals (Sweden)

    Chia-Yen Hung

    2016-06-01

    A 67-year-old Taiwanese female presented to our institution in November 1997 with gastric signet ring cell carcinoma, pT2N0M0, status post subtotal gastrectomy. In February 2003 she was diagnosed with left breast invasive lobular carcinoma status post modified radical mastectomy, pT2N2M0. Further examination in January 2005 revealed proximal transverse colon cancer, Dukes' C2, with status post right hemicolectomy. She achieved disease-free status from all three malignancies after surgical resection and adjuvant chemotherapy for breast and colon cancers sequentially. In November 2011, she complained about sudden onset of gross hematuria for several days. Diagnostic cystoscopy showed a mass lesion over her urinary bladder. Cystoscope-assisted biopsy showed metastatic poorly differentiated adenocarcinoma with signet ring appearance. Herein we have discussed the pathologic role in the diagnosis of metastatic tumor involving a patient with multiple primary cancers. We also explored the epidemiologic risk and potential causal mechanism of patients with multiple primary cancers.

  2. Analysis of prognostic factors in patients with transitional cell carcinoma of the bladder treated with radical cystectomy

    Directory of Open Access Journals (Sweden)

    Antunes Alberto A.

    2006-01-01

    Full Text Available OBJECTIVE: To analyze the results of the treatment of transitional cell carcinoma (TCC of the bladder with radical cystectomy and determine which prognostic factors can be utilized as disease-free survival and cancer-specific survival independent variables. MATERIALS AND METHODS: Medical records of 113 patients submitted to radical cystectomy and bilateral iliac lymphadenectomy between 1993 and 2005 were reviewed. The risk factors analyzed were age, sex, pathological stage, tumor grade, presence of carcinoma in situ and the presence of lymph nodes involvement. RESULTS: After a mean follow-up of 31.7 ? 28.5 months, 46 patients (40.7% presented recurrence and 24 patients (21.2% died due to cancer. Only pathological stage and the lymph nodes involvement became independent variables for recurrence and survival. Patients with T4 stage presented 9.6 times the risk of recurrence of the disease when compared with stage T0 patients (p = 0.010 and the patients with lymph node involvement presented 2.5 times the risk of recurrence (p = 0.047 and 3.1 times the risk of death (p = 0.022 when compared to patients without lymph nodes involvement. CONCLUSIONS: Pathological stage and the involvement of lymph nodes represented more important prognostic variables, and in the presence of advanced stage tumors (T3/T4 and involvement of lymph nodes, the institution of adjuvant treatment should be considered.

  3. uPAR Expression Pattern in Patients with Urothelial Carcinoma of the Bladder

    DEFF Research Database (Denmark)

    Dohn, Line Hammer; Pappot, Helle; Iversen, Benedikte Richter

    2015-01-01

    The objective of the present study was to confirm the expression and localisation pattern of the urokinase-type plasminogen activator receptor (uPAR) focusing on its possible clinical relevance in patients with urothelial neoplasia of the bladder. uPAR is a central molecule in tissue remodelling...... during cancer invasion and metastasis and is an established prognostic marker in various cancer diseases other than bladder cancer. Formalin-fixed and paraffin-embedded tumour-tissue blocks from 186 patients treated with radical cystectomy were analysed. uPAR expression was scored as either negative...... or positive as well as by the actual score. Separate scores were obtained for cancer cells, macrophages and myofibroblasts at the invasive front and in tumour core. We were able to confirm, in an independent patient cohort, the tissue expression and localisation pattern of uPAR as investigated...

  4. Sequential transurethral surgery, multiple drug chemotherapy and radiation therapy for invasive bladder carcinoma: Initial report

    International Nuclear Information System (INIS)

    Cervek, J.; Cufer, T.; Kragelj, B.; Zakotnik, B.; Stanonik, M.

    1993-01-01

    Forty-seven patients with muscle-invasive bladder cancer (T2--T4, Nx, MO) were treated by transurethral resection, followed by 3--4 cycles of combination chemotherapy (methothrexate 30 mg/m2 on days 1, 14; cis-platinum 100 mg/m2 on day 2; vinblastine 3 mg/m2 on days 1, 14; repeated every 21 days), and external beam irradiation (64--66 Gy to the bladder and 40 Gy to the pelvic lymphatics). Complete remission after transurethral resection and chemotherapy was achieved in 24 out of 45 patients (53%). Cystectomy was performed in patients without complete response to transurethral resection and chemotherapy. The therapy was completed as planned in 45/47 patients. After transurethral resection, chemotherapy, and radiation therapy, biopsy proven complete response was achieved in 62% (28/45); Stage T2T3 in 67% (23/24), Stage T4 in 45% (5/11) of patients. Among 19 patients with positive biopsy findings after transurethral resection and chemotherapy, 14 underwent cystectomy. After follow-up of 4--55 months (median 23 months) 75% (34/45) are alive, 68% (31/45) have had their bladders preserved, and 53% (24/45) are free of the primary tumor. The actuarial survival of all 45 patients is 73%. Moderate nausea and vomiting during treatment were common; severe leukopenia and mucositis were observed in five patients. Late side effects such as miction disorders and diarrhea were predominantly mild. Although the observation period has been too short to allow a definitive evaluation of treatment results, the authors feel both from the point of bladder preservation and disease-free survival that the presented treatment approach is successful in a majority of T2T3 patients, whereas a large tumor size (T4) renders this treatment less effective. 17 refs., 4 figs., 4 tabs

  5. Chemoradiotherapy for muscle invading bladder carcinoma. final report of a single institutional organ-sparing program

    International Nuclear Information System (INIS)

    Arias, Fernando; Dominguez, Miguel A.; Martinez, Enrique; Illarramendi, Jose J.; Miquelez, Santiago; Pascual, Ignacio; Marcos, Marta

    2000-01-01

    Purpose: Chemoradiotherapy is becoming an alternative to radical cystectomy among patients with muscle invading bladder cancer. We began a prospective study in 1988 to determine the possibilities of conservative treatment and aiming to improve the results obtained by cystectomy alone in invasive bladder cancer. A combination of methotrexate, vinblastine, adriamycin, and cisplatin (M-VAC), followed by radiotherapy and concomitant cisplatin was used. Methods: Fifty patients with good performance status and with stages T2 to T4 operable untreated invasive bladder cancer were entered in the study. Treatment protocol was as follows: (i) cytoreductive transurethral resection; (ii) two cycles of M-VAC chemotherapy; (iii) radiotherapy, 45 Gy on pelvic volume and, at the same time, 20 mg/m 2 cisplatin on days 1 to 5. Cystoscopic evaluation: if there was a complete response, radiotherapy was completed up to 65 Gy; if there was not a complete response, a cystectomy was performed. Median follow-up of the series was 73 months (18-180 m). Results: Tumor response was as follows: 34 complete responses (68%), 9 partial responses (18%), and 7 nonresponses (14%) were observed. The 5-year overall survival and local control were 48% and 47%, respectively. For the complete responder patient, 5-year survival and local control were 65% and 70%, respectively. Severe toxicity was uncommon. The most frequent were leucopenia and cystitis. No treatment-related deaths occurred with either treatment protocol. Conclusions: Conservative combination treatment may be an acceptable alternative to immediate cystectomy in selected patients with bladder cancer, although a randomized clinical trial would be required to produce definitive results

  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. Chronic urinary tract infection and bladder carcinoma risk: a meta-analysis of case-control and cohort studies.

    Science.gov (United States)

    Akhtar, Saeed; Al-Shammari, Ahmad; Al-Abkal, Jarrah

    2018-02-05

    This meta-analysis of published case-control and cohort studies sought to quantify the magnitude and direction of association between chronic UTI (defined as the infection of the urinary tract that either does not respond to treatment or keeps recurring) and risk of bladder carcinoma (BCa) (i.e., including mainly urothelial carcinoma, squamous cell carcinoma or adenocarcinoma). A literature search was conducted using Medline, Embase, Ovid, Web of Science, Science Direct and Cochrane Library, which was supplemented with manual search of reference lists of the identified articles. Case-control and cohort studies examining UTI as a predictor of BCa risk published through June 2016 were eligible. Using random-effects models, odds ratios (OR) or relative risks (RR) from eligible studies were combined to synthesize summary effect estimates. The included studies were assessed for methodological quality and potential publication bias. Heterogeneity by study characteristics was examined by sub-group and meta-regression analyses. Eighteen case-control and three cohort studies published between 1963 and 2016 were eligible. Random-effects models showed that UTI was significantly associated with an increased BCa risk both in case-control studies (summary OR RE  = 2.33; 95% CI 1.86, 2.92) and cohort studies (summary RR RE  = 2.88; 95% CI 1.20, 6.89). The observed relationship of UTI with an increased BCa risk was independent of the study characteristics considered. No significant publication bias was detected. Chronic UTI was significantly and independently associated with an increased BCa risk. However, due to the presence of high between-study heterogeneity and inconsistent patterns of adjusted confounding effects, more data are needed to clarify the role of chronic UTI in causation of BCa and if established, prompt and effective treatment of UTI may minimize a substantial proportion of BCa risk.

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    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...

  10. 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.

  11. 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.

  12. 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

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

    Directory of Open Access Journals (Sweden)

    Sha N

    2015-11-01

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

  14. Peripheral primitive neuroectodermal tumor of the urinary bladder in an Arab woman with history of squamous cell carcinoma: a case report.

    Science.gov (United States)

    Al Meshaan, Mohd Khaled; Nayef, Marwan; Kwaider, Talal; Otto, Wolfgang; Katchy, Ken C

    2009-04-29

    Peripheral primitive neuroectodermal tumors of the urinary bladder are rare and tend to occur in an older age group than do their counterparts in bones and soft tissue. We report a case of peripheral primitive neuroectodermal tumor of the urinary bladder in a 67-year-old woman of Arab origin. She had undergone transurethral resection followed by chemotherapy because of pulmonary metastasized muscle-invasive squamous cell carcinoma of the bladder in 2005. One year later, she first presented with a history of repeated hematuria in our institution. Performing cystoscopy any tumor could be detected. Control cystoscopy two months later showed a tumor mass of 3 cm in diameter at another location than described for the first tumor. After perforating by transurethral resection partial bladder resection had to be done. Tissue specimen after pathological analysis revealed a peripheral primitive neuroectodermal tumor with tumor cells reactive to cluster of differentiation 99, neuron-specific enolase and S100 protein and stained negative for other markers such as cytokeratins, epithelial membrane antigen, desmin, smooth muscle actin, chromogranin and leucocyte common antigen. Staging computerized tomography was especially free from any hint on organ metastasis, but the patient died due to a cardiac problem only a few months later. To the best of our knowledge, we report the eighth case of bladder peripheral primitive neuroectodermal tumors in literature and the first concerning an Arab patient. It is also the first presentation of a peripheral primitive neuroectodermal tumor patient with a history of squamous cell carcinoma of the bladder. As in other cases, expression of single-chain-type 1 glycoprotein and neural markers was positive and the disease was at an advanced stage at the time of diagnosis.

  15. Urothelial carcinoma associated 1 is a hypoxia-inducible factor-1α-targeted long noncoding RNA that enhances hypoxic bladder cancer cell proliferation, migration, and invasion.

    Science.gov (United States)

    Xue, Mei; Li, Xu; Li, Zhengkun; Chen, Wei

    2014-07-01

    Urothelial carcinoma associated 1 (UCA1) has been identified as an oncogenic long noncoding RNA (lncRNA) that is involved in bladder cancer progression and acts as a diagnostic biomarker for bladder carcinoma. Here, we studied the expression and function of lncRNA-UCA1 in the hypoxic microenvironment of bladder cancer. The expression and transcriptional activity of lncRNA-UCA1 were measured by quantitative real-time polymerase chain reaction and luciferase assays. Cell proliferation and apoptosis were evaluated by MTT assays and flow cytometry. Cell migration and invasion were detected by wound healing, migration, and invasion assays. The binding of hypoxia-inducible factor-1α (HIF-1α) to hypoxia response elements (HREs) in the lncRNA-UCA1 promoter was confirmed by electrophoretic mobility shift assay and chromatin immunoprecipitation. HRE mutations were generated by using a site-directed mutagenesis kit, and HIF-1α knockdown was mediated by small interfering RNA. The effect of HIF-1α inhibition by YC-1 on lncRNA-UCA1 expression was also examined. LncRNA-UCA1 was upregulated by hypoxia in bladder cancer cells. Under hypoxic conditions, lncRNA-UCA1 upregulation increased cell proliferation, migration, and invasion and inhibited apoptosis. The underlying mechanism of hypoxia-upregulated lncRNA-UCA1 expression was that HIF-1α specifically bound to HREs in the lncRNA-UCA1 promoter. Furthermore, HIF-1α knockdown or inhibition could prevent lncRNA-UCA1 upregulation under hypoxia. These findings revealed the mechanism of lncRNA-UCA1 upregulation in hypoxic bladder cancer cells and suggested that effective blocking of lncRNA-UCA1 expression in the hypoxic microenvironment of bladder cancer could be a novel therapeutic strategy.

  16. Relationship of PCNA, C-erbB2 and CD44s expression with tumor grade and stage in urothelial carcinomas of the bladder

    Science.gov (United States)

    Yıldırım, Ayhan; Kösem, Mustafa; Sayar, İlyas; Gelincik, İbrahim; Yavuz, Alparslan; Bozkurt, Aliseydi; Erkorkmaz, Ünal; Bayram, İrfan

    2014-01-01

    In the present study, the intention was to reveal the relationship of histological grade and stage with c-erbB2, CD44s, and PCNA immunoreactivity in bladder urothelial carcinomas (UC). In our study, we evaluated 46 items of transurethral resection material of patients submitted by YYU Faculty of Medicine, Main Department of Pathology, with a mass revealed in their bladder after clinical and radiological studies at our laboratories and who were diagnosed with urothelial carcinomas. PCNA, c-erbB2, and CD44s were applied in an immunohistochemical manner comprised from nine low-malignant potential papillary urothelial neoplasia, 23 low-grade papillary urothelial carcinoma, and 14 high-grade papillary urothelial carcinoma. Immunostaining was scored according to the percentage of positive cells. The immunohistochemical study demonstrated that the c-erbB2 and PCNA staining ratio increased when an increase occurred in stage and grade. The CD44s staining ratio decreased. C-erbB2, PCNA, and CD44s appear to be a useful marker in the assessment of the prognosis and treatment options in urothelial carcinomas. PMID:25035774

  17. 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...

  18. induced acute cytotoxicity in human cervical epithelial carcinoma cells

    African Journals Online (AJOL)

    Molecular basis of arsenite (As +3 )-induced acute cytotoxicity in human cervical epithelial carcinoma cells. ... Libyan Journal of Medicine ... Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and ...

  19. 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.

  20. 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.

  1. Delayed Cystectomy for T1G3 Transitional Cell Carcinoma (TCC) of the Urinary Bladder, NCI Retrospective Case Series

    International Nuclear Information System (INIS)

    FAKHR, I.; EL-HOSSIENY, H.; SALAMA, A.

    2008-01-01

    Aim: We aim to evaluate the National Cancer Institute (NCI) treatment protocol and its outcome regarding recurrence, progression and survival in patients with T1G3 urinary bladder transitional cell carcinoma. Patients and Methods: In a retrospective study, between January 2001 and December 2007, all 34 patients with T1G3 bladder transitional cell carcinoma (TCC), after complete transurethral resection (TURBT), received intravesical BCG as adjuvant therapy. A conservative approach was adopted, whereby those with superficial recurrences were eligible to TURBT, with delayed cystectomy for progression to muscle invasion. Overall, recurrence, and progression-free survival were analyzed. Results: Thirty-three patients were included, 29 were males and 4 were females. The mean age was 61 years (range 35-89 years). Final analysis was made at median follow-up of 15 months (Range of 3-68 months, mean 18 months) for survival. Eleven (33.3%) patients had multi- focal tumors. Associated schistosomiasis was present in 12 (36.6%) patients. Twenty-two (66.67%) patients showed recurrence. Eleven out of these 22 (50.0%) patients progressed to muscle invasion and underwent radical cystectomy. Ten out of 34 (30.3%) patients received post- cystectomy radiotherapy. Two (20.0%) of them, were staged as TNM stage II, 6 (60.0%) as TNM stage III and 2 (20.0%) patients were TNM stage IV. Eight (72.7%) of these 11 patients had post-cystectomy radiotherapy alone; while the 2 (6.0%) other patients with stage IV had adjuvant concomitant Cisplatin and Gemcitabine chemotherapy. Five (14%) patients of those cystectomy patients died of TCC. Three (60%) patients died from metastatic disease (to lung, liver and bone), one patient died from advanced locoregional disease and another patient died from post- operative complications. Among those patients who received radiotherapy alone, 62.5% are alive. Although, we report a biologically more aggressive behavior of T1G3 than that reported by some authors

  2. Plasmacytoid Urothelial Carcinoma of the Urinary Bladder Metastatic to the Duodenum: A Case Report—Diagnostic Relevance of GATA3 Immunohistochemistry

    Directory of Open Access Journals (Sweden)

    Hermann Brustmann

    2017-01-01

    Full Text Available Plasmacytoid urothelial carcinoma (PUC of the urinary bladder is a rare and aggressive subtype of urothelial carcinoma. Its deceptive morphology is characterized by a discohesive growth of cells with plasmacytoid morphology. Since this tumor might be confused with plasmacytoma, lymphoma, or carcinoma variants, appropriate diagnosis in small biopsy samples could be challenging. This study reports the case of a 53-year-old man who presented with frequent nocturnal urgency, without hematuria. A transurethral bladder and a prostate resection specimen displayed infiltration of neoplastic cells in a spray-like discohesive pattern with occasional formation of small irregular nests and cord-like arrangements. The basic morphology of the tumor cells was plasmacytoid, with eccentric nuclei and eosinophilic cytoplasm. Tumor cells grew through the lamina muscularis mucosae, with splintering of the bladder wall musculature and infiltration of prostatic tissue. They displayed strong and diffuse nuclear reactivity for p53 and GATA3. Eight months after surgery, the patient experienced upper abdominal discomfort. A duodenal biopsy showed infiltration of plasmacytoid atypical cells strongly immunoreactive for GATA3, consistent with the previously diagnosed PUC. The patient died eleven months after the primary diagnosis of his PUC of tumor cachexia losing about 50% of his original body weight, furthermore, with ascites and intraperitoneal tumor spread.

  3. Transitional cell carcinoma of urinary bladder with metastasis in lumbar vertebrae and spinal cord compression in an ocelot(Leopardus pardalis

    Directory of Open Access Journals (Sweden)

    Karen Y.R. Nakagaki

    2015-01-01

    Full Text Available This paper reports a case of nonpapillary and infiltrative transitional cell carcinoma (TCC of the urinary bladder with metastasis of lumbar vertebrae and spinal cord compression in an adult female ocelot (Leopardus pardalis, from the Mato Grosso state, Brazil. The ocelot had pelvic limb paralysis and skin ulcers in the posterior region of the body and was submitted to euthanasia procedure. At necropsy was observed a multilobulated and irregular shaped, yellowish to white nodule in the urinary bladder. The nodule had a soft consistency and arised from the mucosa of the urinary bladder extending throughout the muscular layers and the serosa. Nodules of similar appearance infiltrating the vertebral column the at L6 and L7 vertebrae with corresponding spinal canal invasion were also observed. The histological evaluation showed epithelial neoplastic proliferation in the urinary bladder with characteristics of nonpapillary and infiltrative TCC, with positive immunohistochemical staining for pancytokeratin, and strong immunostaining for cytokeratin of low molecular weight, and weak or absent labeling for high molecular weight cytokeratin. This is the first report of TCC of urinary bladder in ocelot in Brazil.

  4. Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients

    Energy Technology Data Exchange (ETDEWEB)

    Pasquier, David, E-mail: d-pasquier@o-lambret.fr [Academic Radiation Oncology Department, Centre Oscar Lambret, Lille (France); Barney, Brandon [Mayo Clinic, Rochester, Minnesota (United States); Sundar, Santhanam [Department of Oncology, Nottingham University Hospitals National Health Service Trust, Nottingham (United Kingdom); Poortmans, Philip [Department of Radiation Oncology, Radboud university medical center, Nijmegen (Netherlands); Villa, Salvador [Radiation Oncology, Catalan Institute of Oncology, H. Universitari Germans Trías, Badalona, Barcelona (Spain); Nasrallah, Haitam [Division of Oncology, Rambam Health Care Campus and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa (Israel); Boujelbene, Noureddine [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland); Ghadjar, Pirus [Department of Radiation Oncology, Bern University Hospital, Bern (Switzerland); Lassen-Ramshad, Yasmin [Department of Oncology, Aarhus University Hospital, Aarhus (Denmark); Senkus, Elżbieta [Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk (Poland); Oar, Andrew [Genesis Cancer Care, Southport (Australia); Roelandts, Martine [Institut Jules Bordet, Brussels (Belgium); Amichetti, Maurizio [Provincial Agency for Proton Therapy, Trento (Italy); Vees, Hansjoerg [Department of Radiation Oncology, Hopital de Sion, Sion (Switzerland); Zilli, Thomas [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Ozsahin, Mahmut [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland)

    2015-07-15

    Purpose: Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. Methods and Materials: Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. Results: The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). Conclusions: The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease

  5. Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients.

    Science.gov (United States)

    Pasquier, David; Barney, Brandon; Sundar, Santhanam; Poortmans, Philip; Villa, Salvador; Nasrallah, Haitam; Boujelbene, Noureddine; Ghadjar, Pirus; Lassen-Ramshad, Yasmin; Senkus, Elżbieta; Oar, Andrew; Roelandts, Martine; Amichetti, Maurizio; Vees, Hansjoerg; Zilli, Thomas; Ozsahin, Mahmut

    2015-07-15

    Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease suggests that conservative treatment is appropriate in this

  6. Telomerase Activity Detected by Quantitative Assay in Bladder Carcinoma and Exfoliated Cells in Urine

    Directory of Open Access Journals (Sweden)

    Roberta Fedriga

    2001-01-01

    Full Text Available Early diagnosis is one of the most determining factors for patient survival. The detection of telomerase activity is a potentially promising tool in the diagnosis of bladder and other types of cancer due to the high expression of this enzyme in tumor cells. We carried out a quantitative evaluation of telomerase activity in urine samples in an attempt to determine a cut-off capable of identifying cancer patients. Telomerase activity was quantified by fluorescence TRAP assay in urine from 50 healthy volunteers and in urine and bioptic tumor samples from 56 previously untreated bladder cancer patients and expressed in arbitrary enzymatic units (AEU. Telomerase activity in urine ranged from 0 to 106 AEU (median 0 in healthy donors and from 0 to 282 AEU (median 87 in patients with cancer. A telomerase expression higher than the cut off value determined by receiver operating characteristic (ROC analysis was observed in 78% of cases, regardless of tumor grade and in 71% (15/21 of cases of nonassessable or negative cytology. The quantitative analysis of telomerase activity in urine enabled us to define cut-off values characterized by different sensitivity and specificity. Cytologic and telomerase determination, used sequentially, enabled us to detect about 90% of tumors.

  7. A Novel Risk Stratification to Predict Local-Regional Failures in Urothelial Carcinoma of the Bladder After Radical Cystectomy

    International Nuclear Information System (INIS)

    Baumann, Brian C.; Guzzo, Thomas J.; He Jiwei; Keefe, Stephen M.; Tucker, Kai; Bekelman, Justin E.; Hwang, Wei-Ting; Vaughn, David J.; Malkowicz, S. Bruce; Christodouleas, John P.

    2013-01-01

    Purpose: Local-regional failures (LF) following radical cystectomy (RC) plus pelvic lymph node dissection (PLND) with or without chemotherapy for invasive urothelial bladder carcinoma are more common than previously reported. Adjuvant radiation therapy (RT) could reduce LF but currently has no defined role because of previously reported morbidity. Modern techniques with improved normal tissue sparing have rekindled interest in RT. We assessed the risk of LF and determined those factors that predict recurrence to facilitate patient selection for future adjuvant RT trials. Methods and Materials: From 1990-2008, 442 patients with urothelial bladder carcinoma at University of Pennsylvania were prospectively followed after RC plus PLND with or without chemotherapy with routine pelvic computed tomography (CT) or magnetic resonance imaging (MRI). One hundred thirty (29%) patients received chemotherapy. LF was any pelvic failure detected before or within 3 months of distant failure. Competing risk analyses identified factors predicting increased LF risk. Results: On univariate analysis, pathologic stage ≥pT3, <10 nodes removed, positive margins, positive nodes, hydronephrosis, lymphovascular invasion, and mixed histology significantly predicted LF; node density was marginally predictive, but use of chemotherapy, number of positive nodes, type of surgical diversion, age, gender, race, smoking history, and body mass index were not. On multivariate analysis, only stage ≥pT3 and <10 nodes removed were significant independent LF predictors with hazard ratios of 3.17 and 2.37, respectively (P<.01). Analysis identified 3 patient subgroups with significantly different LF risks: low-risk (≤pT2), intermediate-risk (≥pT3 and ≥10 nodes removed), and high-risk (≥pT3 and <10 nodes) with 5-year LF rates of 8%, 23%, and 42%, respectively (P<.01). Conclusions: This series using routine CT and MRI surveillance to detect LF confirms that such failures are relatively common in

  8. A Novel Risk Stratification to Predict Local-Regional Failures in Urothelial Carcinoma of the Bladder After Radical Cystectomy

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    Baumann, Brian C. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Guzzo, Thomas J. [Department of Urology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); He Jiwei [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Keefe, Stephen M. [Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Tucker, Kai; Bekelman, Justin E. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Hwang, Wei-Ting [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vaughn, David J. [Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Malkowicz, S. Bruce [Department of Urology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Christodouleas, John P., E-mail: christojo@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2013-01-01

    Purpose: Local-regional failures (LF) following radical cystectomy (RC) plus pelvic lymph node dissection (PLND) with or without chemotherapy for invasive urothelial bladder carcinoma are more common than previously reported. Adjuvant radiation therapy (RT) could reduce LF but currently has no defined role because of previously reported morbidity. Modern techniques with improved normal tissue sparing have rekindled interest in RT. We assessed the risk of LF and determined those factors that predict recurrence to facilitate patient selection for future adjuvant RT trials. Methods and Materials: From 1990-2008, 442 patients with urothelial bladder carcinoma at University of Pennsylvania were prospectively followed after RC plus PLND with or without chemotherapy with routine pelvic computed tomography (CT) or magnetic resonance imaging (MRI). One hundred thirty (29%) patients received chemotherapy. LF was any pelvic failure detected before or within 3 months of distant failure. Competing risk analyses identified factors predicting increased LF risk. Results: On univariate analysis, pathologic stage {>=}pT3, <10 nodes removed, positive margins, positive nodes, hydronephrosis, lymphovascular invasion, and mixed histology significantly predicted LF; node density was marginally predictive, but use of chemotherapy, number of positive nodes, type of surgical diversion, age, gender, race, smoking history, and body mass index were not. On multivariate analysis, only stage {>=}pT3 and <10 nodes removed were significant independent LF predictors with hazard ratios of 3.17 and 2.37, respectively (P<.01). Analysis identified 3 patient subgroups with significantly different LF risks: low-risk ({<=}pT2), intermediate-risk ({>=}pT3 and {>=}10 nodes removed), and high-risk ({>=}pT3 and <10 nodes) with 5-year LF rates of 8%, 23%, and 42%, respectively (P<.01). Conclusions: This series using routine CT and MRI surveillance to detect LF confirms that such failures are relatively common

  9. 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.

  10. Human Epidermal Growth Factor Receptor 2 Overexpression in Micropapillary and Other Variants of Urothelial Carcinoma.

    Science.gov (United States)

    Behzatoğlu, Kemal; Yörükoğlu, Kutsal; Demir, Hale; Bal, Nebil

    2016-06-21

    Human epidermal growth factor receptor 2 (HER2) protein overexpression or gene amplification has been shown in urothelial bladder cancer. This could be helpful when using targeted anti-HER2 therapy on these tumors. To evaluate HER2 immunohistochemical expression in conventional urothelial carcinoma (UC), in situ UC, and UC variants primarily in micropapillary urothelial carcinoma (MPUC). The study evaluated 60 MPUC cases; 25 invasive, 20 low-grade noninvasive, and 10 high-grade noninvasive UC cases; 8 in situ UC cases; and 69 UC variant cases. The immunohistochemistry staining was scored according to recommendations of the American Society of Clinical Oncology/College of American Pathologists 2013 HER2 test guideline established for breast cancer and only 3+ staining was considered HER2 overexpression. HER2 overexpression was determined by 3+ staining. 34 of 60 MPUC cases (56%) showed HER2 overexpression (3+ staining). We observed 3+ staining HER2 overexpression in nine of 25 conventional invasive UC cases (36%), four of eight in situ UC cases (50%), and three of six lipid cell variant cases (50%). 3+ staining HER2 overexpression was not seen in eight glandular, six small cell, and five sarcomatoid variant cases. HER2 overexpression was negative in the 20 low-grade noninvasive UC cases but positive in two of the 10 high-grade noninvasive UC cases (20%). We observed HER2 overexpression most commonly in MPUC cases. We also found HER2 overexpression in conventional invasive and in situ UC cases. Pure in situ UC and conventional invasive UC, especially MPUC, could be candidate tumors for treatment with anti-HER2 antibody (trastuzumab therapy). Targeted therapy has a limited place in treatment of bladder cancer. In this study, human epidermal growth factor receptor 2 (HER2) overexpression in bladder carcinomas was evaluated in a large number of cases. Anti-HER2 therapy could be used in bladder cancers, as in breast and gastric cancers. Copyright © 2016 European

  11. Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma

    International Nuclear Information System (INIS)

    Kato, H.; Torigoe, T.

    1977-01-01

    A heterologous antiserum for human cervical squamous cell carcinoma was prepared and specificity determined by Ouchterlony immunodiffusion and immunofluorescence studies. With this antiserum, a tumor antigen was purified from human cervical squamous cell carcinoma tissue. The specificities of the antigen and the antiserum were then re-examined by a radioimmunoassay method using 125 I-labeled purified antigen. Although normal cervical tissue extract showed a moderate cross-reactivity in the radioimmunoassay, the circulating antigen activity could not be detected in normal women or in several patients with other carcinomas, whereas 27 of 35 patients with cervical squamous cell carcinoma showed detectable serum antigen activity. All patients with advanced stages of cervical squamous cell carcinoma showed detectable antigen levels. These results indicate that there is a quantitative abnormality, at least, of this tumor antigen in patients with cervical squamous cell carcinoma and that the radioimmunoassay for the antigen is a potentially useful tool in clinical care

  12. 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

  13. Molecular markers in transitional cell carcinoma of the bladder: New insights into mechanisms and prognosis

    Directory of Open Access Journals (Sweden)

    Behfar Ehdaie

    2008-01-01

    Full Text Available Urothelial carcinoma is potentially life-threatening and expensive to treat since for many patients, the diagnosis entails a lifetime of surveillance to detect recurrent disease. Advancements in technology have provided an understanding of the molecular mechanisms of carcinogenesis and defined distinct pathways in tumorigenesis and progression. At the molecular level, urothelial carcinoma is being seen as a disease with distinct pathways of carcinogenesis and progression and thus markers of these processes should be used as both diagnostics and predictors of progression and patient outcome. Herein we present a selective overview of the molecular underpinning of urothelial carcinogenesis and progression and discuss the potential for proteins involved in these processes to serve as biomarkers. The discovery of biomarkers has enabled the elucidation of targets for novel therapeutic agents to disrupt the deregulation underlying the development and progression of urothelial carcinogenesis.

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

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    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.

  15. Expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder.

    Science.gov (United States)

    Ai, Xing; Zhang, Xu; Wu, Zhun; Ma, Xin; Ju, Zhenghua; Wang, Baojun; Shi, Taoping

    2007-02-01

    The expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder (TCCB) and its clinical significance were investigated. Immunohistochemistry was used to detect KAI1/CD82 and MRP-1/CD9 protein expression in 52 TCCB specimens. Correlation between the expression of KAI1/CD82 and MRP-1/CD9 to clinicopathologic factors was statistically analyzed. The results showed that the positive rate of KAI1/CD82 and MRP-1/CD9 in TCCB was 50% and 61.5%, respectively. The MRP-1/CD9 and KAI1/CD82 expression was significantly associated with grade of TCCB (PMRP-1/CD9 or KAI1/CD82 expression and clinical stage of TCCB (P>0.05). The expression level of MRP-1/CD9 and KAI1/CD82 in recurrent TCCB samples was lower than that in non-recurrent samples (PMRP-1/CD9 expression was statistically significant (r=0.316, PMRP-1/CD9 expression may be important prognostic indicators and potentially useful for assessing the biological behavior of TCCB.

  16. Crude mortality and loss of life expectancy of patients diagnosed with urothelial carcinoma of the urinary bladder in Norway.

    Science.gov (United States)

    Andreassen, Bettina K; Myklebust, Tor Å; Haug, Erik S

    2017-02-01

    Reports from cancer registries often lack clinically relevant information, which would be useful in estimating the prognosis of individual patients with urothelial carcinoma of the urinary bladder (UCB). This article presents estimates of crude probabilities of death due to UCB and the expected loss of lifetime stratified for patient characteristics. In Norway, 10,332 patients were diagnosed with UCB between 2001 and 2010. The crude probabilities of death due to UCB were estimated, stratified by gender, age and T stage, using flexible parametric survival models. Based on these models, the loss in expectation of lifetime due to UCB was also estimated for the different strata. There is large variation in the estimated crude probabilities of death due to UCB (from 0.03 to 0.76 within 10 years since diagnosis) depending on age, gender and T stage. Furthermore, the expected loss of life expectancy is more than a decade for younger patients with muscle-invasive UCB and between a few months and 5 years for nonmuscle-invasive UCB. The suggested framework leads to clinically relevant prognostic risk estimates for individual patients diagnosed with UCB and the consequence in terms of loss of lifetime expectation. The published probability tables can be used in clinical praxis for risk communication.

  17. The Ileal W-Shaped Neo bladder Following Radical Cystectomy for Carcinoma of the Urinary Bladder: Experience and Results of 50 Cases

    International Nuclear Information System (INIS)

    Bassiouny, M.; Helmy, A.; Amin, A.; Aboul Kassem, H.

    2003-01-01

    The optimal urinary bladder substitute for patients undergoing radical cystectomy is still controversial. The ideal reservoir should provide a large storage capacity at low pressure achieving effective continence with less frequency and minimal renal reflux. In this study we present our experience with W-shaped ileal neo bladder following radical cystectomy. Material and Methods: Between April 1995 and September 1999, a total of 50 male patients underwent lower urinary tract reconstruction following radical cysto prostatectomy by means of ileal W-shaped neo bladder. All patients had invasive bladder cancer proved by preoperative cystoscopy. Their mean age was 45.5 years. The median neo bladder pouch capacity was 420 ml; daytime continence rate was 89.4%, while nighttime continence was noticed in 53.3% of cases. The uretero intestinal anastomoses were performed employing Le Duc technique in all patients. Renal units remained normal in 25 out of 30 evaluated patients. Dilatation of the pelvicalyceal system and the ureter, either unilateral or bilateral occurred in 5/30 of patients (16.6%). These were due to stricture at the urethro or uretero-pouch anastomosis that needed transurethral urethrotomy or revision of the anastomosis; however, renal functions were maintained in all patients. There were three postoperative mortalities (6%) and the early postoperative complications included urinary leakage (6%), prolonged ileus (10%) and deep venous thrombosis (4%). Late complications related to the neo bladder were acceptable including metabolic acidosis (2%). The ileal W-shaped neo bladder is a good choice for male patients after radical cystectomy, provided that there is no evidence of prostatic or urethral tumor invasion

  18. 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.

  19. 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.

  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.

  1. 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

  2. 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

  3. Study of false positives in 5-ALA induced photodynamic diagnosis of bladder carcinoma

    Science.gov (United States)

    Draga, Ronald O. P.; Grimbergen, Matthijs C. M.; Kok, Esther T.; Jonges, Trudy G. N.; Bosch, J. L. H. R.

    2009-02-01

    Photodynamic diagnosis (PDD) is a technique that enhances the detection of tumors during cystoscopy using a photosensitizer which accumulates primarily in cancerous cells and will fluoresce when illuminated by violetblue light. A disadvantage of PDD is the relatively low specificity. In this retrospective study we aimed to identify predictors for false positive findings in PDD. Factors such as gender, age, recent transurethral resection of bladder tumors (TURBT), previous intravesical therapy (IVT) and urinary tract infections (UTIs) were examined for association with the false positive rates in a multivariate analysis. Data of 366 procedures and 200 patients were collected. Patients were instilled with 5-aminolevulinic acid (5-ALA) intravesically and 1253 biopsies were taken from tumors and suspicious lesions. Female gender and TURBT are independent predictors of false positives in PDD. However, previous intravesical therapy with Bacille Calmette-Guérin is also an important predictor of false positives. The false positive rate decreases during the first 9-12 weeks after the latest TURBT and the latest intravesical chemotherapy. Although shortly after IVT and TURBT false positives increase, PDD improves the diagnostic sensitivity and results in more adequate treatment strategies in a significant number of patients.

  4. On the post-operative radiotherapy of carcinoma of the bladder

    International Nuclear Information System (INIS)

    Heidrich, V.

    1981-01-01

    The results of 330 tumours of the bladder treated in the Marburg Radiological Clinic from 1957 until 1977 are evaluated. Of these 330 patients, 227 were male, 53 female. The average age at the beginning of the treatment was 65,25 years. As irradiation methods, we chose vertical and pendulum irradiation with a telegamma equipment (Gammatron I, Siemens). The equipment was programmed to 60 Gy in a 5-day rhythm with single doses of 1.5 Gy. The fractioning of the focal dose used leads, in addition to an increased curability, also to an improved tolerance: in only 3.03% of the cases severe side effects are seen in the form of radiovasculopathy and necrotising radiocystitis resp. which necessitate a cystectomy. The percentage of the total range of side effects (22.7%) could also be reduced considerably. The survival rate was 69.4% after one year, 35.4% after 3 years, and 25.6% after five years. There was a direct relation between the rates of survival and the focal dose. Within the gammatron technique, the three-fields-method was found to be slightly superior to the pendulum and the wedge filter methods. (orig./MG) [de

  5. Fatores de risco em carcinomas de células transicionais da bexiga: risk factors Transitional cell carcinoma of the bladder

    Directory of Open Access Journals (Sweden)

    Ricardo Brianezi Tiraboschi

    2002-01-01

    Full Text Available OBJETIVO: Investigar alguns dados epidemiológicos do câncer vesical bem como fatores de risco. MÉTODOS: Foram selecionados 125 pacientes atendidos no período 1980-2002, com idade média de 63,6±11,3 anos, sendo 97 (77,6% homens e 28 (22,4% mulheres. As proporções de tumores G1, G2 e G3 foram: 48%, 35,2% e 16,8%. As proporções dos estádios da lesão primária foram: pTa-1 - 85 ( 68% e pT2-4 - 40 ( 32%. Entre os pacientes com tumores superficiais houve recidiva em 41 (48,2%. RESULTADOS: O grau da lesão primária mostrou relação com o estádio T (pOBJECTIVE: To analyse some epidemiological data of patients with transitional cell carcinoma of the bladder (TCC and the predictive value of conventional risk factors. METHODS: From 1980 to 2002, 125 patients were treated at our hospital and selected retrospectively for this study. The series mean age was 63,6±11,3 years, being 77.6% males and 22.4% females. The proportions of G!, G2 and G3 TCC were: 48%, 35.2% and 16.8%. The T stage was: pTa-1 - 85 (68% and pT2-4 - 40 (32%. Superficial tumors were treated by TUR alone or plus BCG (>G1, and the invasives ones by radical cystectomy. The vesical reccurence rate of superficial TCC was 48.2%. RESULTS: TCC grade showed a positive association with T stage (p<0.0001 and patient survival (p<0.0001, but not with local bladder reccurence of superficial tumors (p=0.72. The T stage also showed a strong correlation with patient survival (p<0.0001. CONCLUSION: The TCC is more common in male than in female with mean age of 63.2 years. The tumor grading and staging exhibited as strong predictive value for disease progression and patient survival.

  6. 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

  7. Radiotherapy may improve overall survival of patients with T3/T4 transitional cell carcinoma of the renal pelvis or ureter and delay bladder tumour relapse

    Directory of Open Access Journals (Sweden)

    Wu Li-Li

    2011-07-01

    Full Text Available Abstract Background Since transitional cell carcinoma (TCC of the upper urinary tract is a relatively uncommon malignancy, the role of adjuvant radiotherapy is unknown. Methods We treated 133 patients with TCC of the renal pelvis or ureter at our institution between 1998 and 2008. The 67 patients who received external beam radiotherapy (EBRT following surgery were assigned to the radiation group (RT. The clinical target volume included the renal fossa, the course of the ureter to the entire bladder, and the paracaval and para-aortic lymph nodes, which were at risk of harbouring metastatic disease in 53 patients. The tumour bed or residual tumour was targeted in 14 patients. The median radiation dose administered was 50 Gy. The 66 patients who received intravesical chemotherapy were assigned to the non-radiation group (non-RT. Results The overall survival rates for the RT and non-RT groups were not significantly different (p = 0.198. However, there was a significant difference between the survival rates for these groups based on patients with T3/T4 stage cancer. A significant difference was observed in the bladder tumour relapse rate between the irradiated and non-irradiated bladder groups (p = 0.004. Multivariate analysis indicated that improved overall survival was associated with age grade 3 hematologic symptoms also occurred. Conclusion EBRT may improve overall survival for patients with T3/T4 cancer of the renal pelvis or ureter and delay bladder tumour recurrence in all patients.

  8. 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.

  9. MicroRNA profiling of dogs with transitional cell carcinoma of the bladder using blood and urine samples.

    Science.gov (United States)

    Kent, Michael S; Zwingenberger, Allison; Westropp, Jodi L; Barrett, Laura E; Durbin-Johnson, Blythe P; Ghosh, Paramita; Vinall, Ruth L

    2017-11-15

    Early signs of canine transitional cell carcinoma (TCC) are frequently assumed to be caused by other lower urinary tract diseases (LUTD) such as urinary tract infections, resulting in late diagnosis of TCC which could be fatal. The development of a non-invasive clinical test for TCC could dramatically reduce mortality. To determine whether microRNAs (miRNAs) can be used as non-invasive diagnostic biomarkers, we assessed miRNA expression in blood and/or urine from dogs with clinically normal bladders (n = 28), LUTD (n = 25), and TCC (n = 17). Expression levels of 5 miRNA associated with TCC pathophysiology (miR-34a, let-7c, miR-16, miR-103b, and miR-106b) were assessed by quantitative real-time PCR. Statistical analyses using ranked ANOVA identified significant differences in miR-103b and miR-16 levels between urine samples from LUTD and TCC patients (miR-103b, p = 0.002; and miR-16, p = 0.016). No statistically significant differences in miRNA levels were observed between blood samples from LUTD versus TCC patients. Expression levels of miR-34a trended with miR-16, let-7c, and miR-103b levels in individual normal urine samples, however, this coordination was completely lost in TCC urine samples. In contrast, co-ordination of miR-34a, miR-16, let-7c, and miR-103b expression levels was maintained in blood samples from TCC patients. Our combined data indicate a potential role for miR-103b and miR-16 as diagnostic urine biomarkers for TCC, and that further investigation of miR-103b and miR-16 in the dysregulation of coordinated miRNA expression in bladder carcinogenesis is warranted.

  10. 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

  11. Combined effect of tumor necrosis factor-alpha and ionizing radiation on the induction of apoptosis in 5637 bladder carcinoma cells

    International Nuclear Information System (INIS)

    Baierlein, S.A.; Distel, L.; Sieber, R.; Weiss, C.; Roedel, C.; Sauer, R.; Roedel, F.

    2006-01-01

    Background and Purpose: Apoptosis can be induced by distinct but overlapping pathways. Ionizing radiation induces apoptosis by an ''intrinsic'', mitochondria-dependent pathway. Ligation of tumor necrosis factor-(TNF-)α, FAS (CD95) or TRAIL receptors are typical representatives of an extrinsic, death-receptor-mediated pathway. In this study the effect of irradiation, treatment with the cytokine TNF-α, or a combination of both on the induction of apoptosis and clonogenic survival of bladder carcinoma cells was investigated. Material and Methods: 5637 bladder carcinoma cells were treated with different concentrations of recombinant TNF-α (0-10 ng/ml), irradiated with single doses ranging from 0.5 to 10 Gy, or a combination of both modalities. Apoptotic cells were quantified by the TUNEL assay up to 96 h following treatment, clonogenic cell survival by a clonogenic assay. Synergistic effects of both modalities were evaluated using isobolographic analysis. Results: Irradiation of 5637 carcinoma cells resulted in a discontinuous dose dependence of the apoptotic fraction with a pronounced increase in the range of 0-2 Gy and a slighter increase at 2-10 Gy. The percentage of apoptotic carcinoma cells also increased continuously after treatment with lower concentrations of TNF-α reaching a plateau at concentrations of 5.0-10.0 ng/ml. Isobolographic analysis revealed a supraadditive interrelationship between irradiation and TNF-α in the range between 0.005 and 0.5 ng/ml, and an additive effect for TNF-α concentrations > 0.5 ng/ml. The additive effects were confirmed in clonogenic survival assays with reduced survival fractions following combined TNF-α administration and irradiation. Conclusion: The combination of two apoptosis-inducing modalities resulted in a synergistic effect on the induction of apoptosis in 5637 bladder carcinoma cells. Although a radiosensitizing effect still has to be proven in animal models, combined-modality treatment may increase the

  12. Human papillomas virus infection in the case of larynx carcinoma

    International Nuclear Information System (INIS)

    Makowska, W.; Rogozinski, T.; Zawadowski, J.; Waloryszak, B.

    1993-01-01

    The case of 59 year old man treated (with surgery and radiotherapy) for larynx carcinoma was presented. The potentially oncogenic human papillomavirus type 16/18 was detected in the tissue surrounding the tumor. (author)

  13. 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.

  14. 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.

  15. Human papilloma virus prevalence in laryngeal squamous cell carcinoma.

    Science.gov (United States)

    Gungor, A; Cincik, H; Baloglu, H; Cekin, E; Dogru, S; Dursun, E

    2007-08-01

    To determine the prevalence and type of human papilloma virus deoxyribonucleic acid (DNA) in cases of laryngeal squamous cell carcinoma. We analysed the prevalence of human papilloma virus infection in archived paraffin block specimens taken from 99 cases of laryngeal squamous cell carcinoma between 1990 and 2005, using polymerase chain reaction techniques. Biopsy specimens from five proven verrucous skin lesions were used as positive controls, and peripheral blood samples from five healthy volunteers were used as negative controls. Four test samples were found to have inadequate deoxyribonucleic acid purity and were therefore excluded from the study. Human papilloma virus deoxyribonucleic acid was detected in seven of 95 cases of laryngeal squamous cell carcinoma (7.36 per cent). Human papilloma virus genotyping revealed double human papilloma virus infection in three cases and single human papilloma virus infection in the remaining four cases. The human papilloma virus genotypes detected were 6, 11 and 16 (the latter detected in only one case). In our series, a very low human papilloma virus prevalence was found among laryngeal squamous cell carcinoma cases. The human papilloma virus genotypes detected were mostly 6 and/or 11, and 16 in only one case. To the best of our knowledge, this is the first report of human papilloma virus prevalence in laryngeal squamous cell carcinoma, based on polymerase chain reaction genotyping in a Turkish population.

  16. Hypoxia regulates the expression and localization of CCAAT/enhancer binding protein α by hypoxia inducible factor-1α in bladder transitional carcinoma cells.

    Science.gov (United States)

    Xue, Mei; Li, Xu; Chen, Wei

    2015-08-01

    Hypoxia inducible factor-1α (HIF-1α) is overexpressed in various types of solid tumor in humans, including bladder cancer. HIF-1α regulates the expression of a series of genes, which are involved in cell proliferation, differentiation, apoptosis, angiogenesis, migration and invasion and represents a potential therapeutic target for the treatment of human cancer. Despite extensive investigation of the effects of HIF-1α in the progression and metastasis of bladder cancer, the possible regulatory mechanisms underlying the effects of HIF-1α on bladder cancer cell proliferation and differentiation remain to be elucidated. It has been suggested that the transcription factor CCAAT/enhancer binding protein α (C/EBPα) acts as a tumor suppressor in several types of cancer cell, which are involved in regulating cell differentiation, proliferation and apoptosis. The present study confirmed that, in bladder cancer cells, the expression and localization of C/EBPα was regulated by hypoxia through an HIF-1α -dependent mechanism, which may be significant in bladder cancer cell proliferation and differentiation. The 5637 and T24 bladder cancer cell lines were incubated under normoxic and hypoxic conditions. The expression levels of HIF-1α and C/EBPα were detected by reverse transcription-quantitative polymerase chain reaction, western blotting and immunofluorescence analysis. The results revealed that, under hypoxic conditions, the protein expression levels of HIF-1α were markedly upregulated, but the mRNA levels were not altered. However, the mRNA and protein levels of C/EBPα were significantly reduced. The present study further analyzed the subcellular localization of C/EBPα, which was markedly decreased in the nuclei under hypoxic conditions. Following HIF-1α small interference RNA silencing of HIF-1α, downregulation of C/EBPα was prevented in the bladder cancer cells cultured under hypoxic conditions. In addition, groups of cells treated with 3-(5'-hydroxymethyl

  17. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    OpenAIRE

    Barkla, D. H.; Whitehead, R. H.; Foster, H.; Tutton, P. J.

    1988-01-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting f...

  18. Advanced small cell carcinoma of the bladder: clinical characteristics, treatment patterns and outcomes in 960 patients and comparison with urothelial carcinoma

    International Nuclear Information System (INIS)

    Geynisman, Daniel M.; Handorf, Elizabeth; Wong, Yu-Ning; Doyle, Jamie; Plimack, Elizabeth R.; Horwitz, Eric M.; Canter, Daniel J.; Uzzo, Robert G.; Kutikov, Alexander; Smaldone, Marc C.

    2015-01-01

    To describe the clinical characteristics, treatment patterns and outcomes in advanced small cell bladder cancer (aSCBC) patients and compare to those with urothelial carcinoma (UC). Individuals in the National Cancer Data Base with a diagnosis of either nodal (TxN+M0) or distant metastatic (TxNxM1) disease were identified from 1998 to 2010. We assessed the relationships between stage, treatment modalities and survival in the aSCBC cohort and compared these to UC patients. In the 960 patient aSCBC cohort (62% M1), 50% received palliative therapy alone, 68% in M1 versus 21% in M0 groups (P < 0.0001). Single modality local therapy (15%) and surgical (21%) or radiation-based (14%) multimodal therapy (MMT) were used in the other 50%. Cystectomy-based MMT was utilized in 45% of N+M0 versus 6.4% of NxM1 patients (P < 0.0001). Median overall survival (OS) for aSCBC patients was 8.6 months; 13.0 months in N+M0 versus 5.3 months in NxM1 patients (P < 0.0001). Survival was similar between TxN1M0 and TxN2-3M0 patients (14.8 months vs. 12.1 months, P = 0.15). Urothelial carcinoma patients (n = 27,796, 45% M1) lived longer compared to aSCBC patients in the N+M0 group (17.3 months vs. 13.0 months, P = 0.0007). There were not clinically significant differences in OS between UC and aSCBC patients in the M1 group. Advanced SCBC is a rare disease with a poor survival and palliative therapy is common, especially in M1 patients. In comparison to UC, the outcomes for aSCBC patients are worse in those with lymph node only involvement but similar in those with distant disease

  19. Cytopathologic differential diagnosis of low-grade urothelial carcinoma and reactive urothelial proliferation in bladder washings: a logistic regression analysis.

    Science.gov (United States)

    Cakir, Ebru; Kucuk, Ulku; Pala, Emel Ebru; Sezer, Ozlem; Ekin, Rahmi Gokhan; Cakmak, Ozgur

    2017-05-01

    Conventional cytomorphologic assessment is the first step to establish an accurate diagnosis in urinary cytology. In cytologic preparations, the separation of low-grade urothelial carcinoma (LGUC) from reactive urothelial proliferation (RUP) can be exceedingly difficult. The bladder washing cytologies of 32 LGUC and 29 RUP were reviewed. The cytologic slides were examined for the presence or absence of the 28 cytologic features. The cytologic criteria showing statistical significance in LGUC were increased numbers of monotonous single (non-umbrella) cells, three-dimensional cellular papillary clusters without fibrovascular cores, irregular bordered clusters, atypical single cells, irregular nuclear overlap, cytoplasmic homogeneity, increased N/C ratio, pleomorphism, nuclear border irregularity, nuclear eccentricity, elongated nuclei, and hyperchromasia (p ˂ 0.05), and the cytologic criteria showing statistical significance in RUP were inflammatory background, mixture of small and large urothelial cells, loose monolayer aggregates, and vacuolated cytoplasm (p ˂ 0.05). When these variables were subjected to a stepwise logistic regression analysis, four features were selected to distinguish LGUC from RUP: increased numbers of monotonous single (non-umbrella) cells, increased nuclear cytoplasmic ratio, hyperchromasia, and presence of small and large urothelial cells (p = 0.0001). By this logistic model of the 32 cases with proven LGUC, the stepwise logistic regression analysis correctly predicted 31 (96.9%) patients with this diagnosis, and of the 29 patients with RUP, the logistic model correctly predicted 26 (89.7%) patients as having this disease. There are several cytologic features to separate LGUC from RUP. Stepwise logistic regression analysis is a valuable tool for determining the most useful cytologic criteria to distinguish these entities. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  20. Long non-coding RNA urothelial carcinoma-associated 1 as a tumor biomarker for the diagnosis of urinary bladder cancer.

    Science.gov (United States)

    Wang, Zichun; Wang, Xiaoxiong; Zhang, Daming; Yu, Yongchun; Cai, Licheng; Zhang, Cheng

    2017-06-01

    To investigate the diagnostic value of urothelial carcinoma-associated 1 as a urine biomarker in urinary bladder cancer patients by performing a comprehensive meta-analysis. A comprehensive literature search was conducted by the databases PubMed, Embase, Cochrane Library, China Knowledge Resource Integrated, and Web of Science. The quality of eligible studies was scored with the Quality Assessment of Diagnostic Accuracy Studies. The bivariate meta-analysis model was used to pool the sensitivity, specificity, likelihood ratio, and diagnostic odds ratio. Receiver operating characteristic curves and hierarchical summary receiver operating characteristic models were employed to check the overall test performance in this meta-analysis. Seven publications involving 678 patients and 563 controls were included in this meta-analysis. The pooled sensitivity was 0.84 (95% confidence interval: 0.80-0.88), specificity was 0.87 (95% confidence interval: 0.75-0.94), positive likelihood ratio was 6.5 (95% confidence interval: 3.10-13.62), negative likelihood ratio was 0.18 (95% confidence interval: 0.13-0.25), and diagnostic odds ratio was 36 (95% confidence interval: 13-99). The area under the summary receiver operating characteristic curve was 0.89 (95% confidence interval: 0.86-0.91). Our results indicated that urothelial carcinoma-associated 1 was a potential diagnostic biomarker with good specificity and sensitivity in urinary bladder cancer. Further prospective studies with larger cohorts are necessary to evaluate the diagnostic accuracy of urothelial carcinoma-associated 1 for urinary bladder cancer.

  1. FGFR3 expression in primary and metastatic urothelial carcinoma of the bladder

    International Nuclear Information System (INIS)

    Guancial, Elizabeth A; Werner, Lillian; Bellmunt, Joaquim; Bamias, Aristotle; Choueiri, Toni K; Ross, Robert; Schutz, Fabio A; Park, Rachel S; O'Brien, Robert J; Hirsch, Michelle S; Barletta, Justine A; Berman, David M; Lis, Rosina; Loda, Massimo; Stack, Edward C; Garraway, Levi A; Riester, Markus; Michor, Franziska; Kantoff, Philip W; Rosenberg, Jonathan E

    2014-01-01

    While fibroblast growth factor receptor 3 (FGFR3) is frequently mutated or overexpressed in nonmuscle-invasive urothelial carcinoma (UC), the prevalence of FGFR3 protein expression and mutation remains unknown in muscle-invasive disease. FGFR3 protein and mRNA expression, mutational status, and copy number variation were retrospectively analyzed in 231 patients with formalin-fixed paraffin-embedded primary UCs, 33 metastases, and 14 paired primary and metastatic tumors using the following methods: immunohistochemistry, NanoString nCounterTM, OncoMap or Affymetrix OncoScanTM array, and Gain and Loss of Analysis of DNA and Genomic Identification of Significant Targets in Cancer software. FGFR3 immunohistochemistry staining was present in 29% of primary UCs and 49% of metastases and did not impact overall survival (P = 0.89, primary tumors; P = 0.78, metastases). FGFR3 mutations were observed in 2% of primary tumors and 9% of metastases. Mutant tumors expressed higher levels of FGFR3 mRNA than wild-type tumors (P < 0.001). FGFR3 copy number gain and loss were rare events in primary and metastatic tumors (0.8% each; 3.0% and 12.3%, respectively). FGFR3 immunohistochemistry staining is present in one third of primary muscle-invasive UCs and half of metastases, while FGFR3 mutations and copy number changes are relatively uncommon

  2. 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.

  3. 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....

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

    Science.gov (United States)

    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.

  5. 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.

  6. 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 ...

  7. Upper Tract Urothelial Carcinomas Accompanied by Previous or Synchronous Nonmuscle-Invasive Bladder Cancer and Preoperative Hydronephrosis Might Have Worse Oncologic Outcomes After Radical Nephroureterectomy.

    Science.gov (United States)

    Liang, Chengcai; Chi, Runmin; Huang, Liqun; Wang, Jinliang; Liu, Hailong; Xu, Ding; Qian, Subo; Qian, Xiaoqiang; Qi, Jun

    2016-10-01

    The purpose of the study was to identify predictors of clinicopathologic features and oncologic outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy (RNU). The medical records of 172 patients treated with RNU from January 2001 to September 2014 were retrospectively reviewed. Logistic regression and survival analysis methodology were respectively used to evaluate predictors of clinicopathologic features and oncologic outcomes. Of the enrolled 172 patients, 80 (46.5%) had renal pelvic tumors, 67 (39%) had ureteral tumors, and the remaining 25 (14.5%) patients had multifocal tumors. Compared with patients with renal pelvic tumors, those with ureteral and multifocal tumors were more likely to have previous or synchronous nonmuscle-invasive bladder cancer (NMIBC) and severe hydronephrosis (P = .001 and P hydronephrosis independently predicted worse renal function and positive lymph node or lymphovascular invasion status (P = .001 and P = .007, respectively). Moreover, severe hydronephrosis was an independent risk factor for overall survival and cancer-specific survival in multivariate analysis (P = .025 and P = .045, respectively). Multifocality and previous or synchronous NMIBC were significantly associated with bladder-recurrence-free survival (P = .023 and P = .001, respectively). Upper tract urothelial carcinoma accompanied by previous or synchronous NMIBC and preoperative severe hydronephrosis could have worse oncologic outcomes after RNU. These common accompanied diagnoses could be valuable for guiding preoperative planning and postoperative adjuvant therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Choroidal and Cutaneous Metastasis from Urothelial Carcinoma of the Bladder after Radical Cystectomy: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Yozo Mitsui

    2014-01-01

    Full Text Available Bladder cancer is the second most common genitourinary malignancy and has variable metastatic potential; however, choroidal and cutaneous metastases are extremely rare. Generally, a patient with these uncommon metastases has a very poor prognosis. We present a bladder cancer patient with a visual disorder in the right eye and multiple nodules on head and lower abdomen that developed 17 months after a radical cystectomy. These symptoms were determined to be caused by choroidal and cutaneous metastasis of bladder cancer. Although two cycles of combination chemotherapy were performed, the patient died 5 months after diagnosis of multiple metastases.

  9. PRIMARY CARCINOMA OF THE GALL BLADDER: REVIEW AND STUDY OF EIGHTY CASES IN EMAM-KHOMEINI MEDICAL CENTER

    Directory of Open Access Journals (Sweden)

    M.A.RASHED-MOHASSEL

    1982-05-01

    Full Text Available In a r etrospective s t udy on the c ancer o f the gal l bladder, done in Iran, it s e ems tha t it compr ises 0 . 36% o f a ll the malignant tumors . 1 .7 5% of the patients were fema les and the maximum incidenc e wa s in t he s i x th decade of l i f e. It was interesting t o note that the age ratio bet ween t he males and f ema le s reverses with t he advance o f a ge, s o at the 7th and 8t h decade of life , the inciden ce o f the disease 1n males wa s muc h highe r than f emales."nAt the 8th dec ade , the nun~er of male patients was twice as f emales . The presenting symptoms in most c a ses were; pain,j aun- d ice, l o s s o f we i gh t , and in a f ew c ases t here was a hist or y of long l asting s~np tom s , re fe r able t o the bili a ry s ystem. After admission and surgical opening of the abdomen , 60% o f patie nts we re c ons i dere d ino perable. Al l the pat ients suf fe ring f rom anaplast ic carcinoma , which comprised 5% of all case s , were female and had a long l ast i ng history of gall b ladder infe c tions. The prevalence o f stone f ormation in g a l l blad der malignancie s i s a known f act but whether t he c au s e of thi s coincidenc e i s due t o some factors, suc h as irritation dysp:asia,or only CO~~ Ibi na tion o f t hese , is not def i n i t ly known.

  10. Problems in early diagnosis of bladder cancer in a spinal cord injury patient: Report of a case of simultaneous production of granulocyte colony stimulating factor and parathyroid hormone-related protein by squamous cell carcinoma of urinary bladder

    Directory of Open Access Journals (Sweden)

    Singh Gurpreet

    2002-08-01

    Full Text Available Abstract Background Typical symptoms and signs of a clinical condition may be absent in spinal cord injury (SCI patients. Case presentation A male with paraplegia was passing urine through penile sheath for 35 years, when he developed urinary infections. There was no history of haematuria. Intravenous urography showed bilateral hydronephrosis. The significance of abnormal outline of bladder was not appreciated. As there was large residual urine, he was advised intermittent catheterisation. Serum urea: 3.5 mmol/L; creatinine: 77 umol/L. A year later, serum urea: 36.8 mmol/l; creatinine: 632 umol/l; white cell count: 22.2; neutrophils: 18.88. Ultrasound: bilateral hydronephrosis. Bilateral nephrostomy was performed. Subsequently, blood tests showed: Urea: 14.2 mmol/l; Creatinine: 251 umol/l; Adjusted Calcium: 3.28 mmol/l; Parathyroid hormone: A repeat ultrasound scan demonstrated a tumour arising from right lateral wall; biopsy revealed squamous cell carcinoma. In view of persistently high white cell count and high calcium level, immunohistochemistry for G-CSF and PTHrP was performed. Dense staining of tumour cells for G-CSF and faintly positive staining for C-terminal PTHrP were observed. This patient expired about five months later. Conclusion This case demonstrates how delay in diagnosis of bladder cancer could occur in a SCI patient due to absence of characteristic symptoms and signs.

  11. Pretreatment Neutrophil-Lymphocyte Ratio as a Predictor in Bladder Cancer and Metastatic or Unresectable Urothelial Carcinoma Patients: a Pooled Analysis of Comparative Studies.

    Science.gov (United States)

    Wu, Shuiqing; Zhao, Xiaokun; Wang, Yinhuai; Zhong, Zhaohui; Zhang, Lei; Cao, Jian; Ai, Kai; Xu, Ran

    2018-01-01

    Emerging studies have shown that the neutrophil-lymphocyte ratio (NLR) is a potential predictor in various tumors. Our study was conducted to assess the prognostic value of the pretreatment NLR in bladder cancer and metastatic or unresectable urothelial carcinoma (mUC or uUC) patients up to July 2017. The correlation between the pretreatment NLR and pathological characteristics was also evaluated in bladder cancer patients. The hazard ratio (HR) and odds ratio (OR) with the 95% confidence interval (CI) were extracted or calculated from the included studies for further pooled analysis. A total of 21 studies were included in a pooled analysis. The pooled results indicated that a high pretreatment NLR was associated with reduced overall survival (OS) (HR=1.27, 95% CI=1.12-1.43), relapse-free survival (RFS) (HR=1.41, 95% CI=1.23-1.60), progression-free survival (PFS) (HR=1.75, 95% CI=1.36-2.15), disease-specific survival (DSS) and cancer-specific survival (CSS) (HR=1.27, 95% CI=1.19-1.35) in the bladder cancer patients. Additionally, an elevated pretreatment NLR suggested a worse OS rate in the mUC or uUC patients (HR=1.63, 95% CI=1.34-1.91). The pooled ORs and 95% CIs showed that a high pretreatment NLR could be a risk indicator for certain pathological features, such as lymphovascular invasion, a positive margin status and advanced tumor stage. our results showed that a high pretreatment NLR predicted poor prognosis in bladder cancer, mUC and uUC patients. © 2018 The Author(s). Published by S. Karger AG, Basel.

  12. Treatment of carcinoma in situ of the urinary bladder with an alpha-emitter immunoconjugate targeting the epidermal growth factor receptor: a pilot study.

    Science.gov (United States)

    Autenrieth, Michael E; Seidl, Christof; Bruchertseifer, Frank; Horn, Thomas; Kurtz, Florian; Feuerecker, Benedikt; D'Alessandria, Calogero; Pfob, Christian; Nekolla, Stephan; Apostolidis, Christos; Mirzadeh, Saed; Gschwend, Jürgen E; Schwaiger, Markus; Scheidhauer, Klemens; Morgenstern, Alfred

    2018-07-01

    Patients with carcinoma in situ (CIS) of the bladder refractory to bacillus Calmette-Guérin (BCG) treatment are usually treated with cystectomy. Therefore, new treatment options with preservation of the urinary bladder are needed. The objective of the study was to investigate the feasibility, safety and efficacy of a novel targeted alpha-emitter immunotherapy for CIS after BCG treatment failure. A pilot study was conducted in 12 patients (age range 64-86 years, ten men, two women) with biopsy-proven CIS of the bladder refractory to BCG treatment. The patients were treated intravesically with a single instillation (one patient was treated twice) of the alpha-emitter 213 Bi coupled to an anti-EGFR antibody (366-821 MBq). The primary aims of the study were to determine the feasibility of treatment with the 213 Bi-immunoconjugate and evaluation of adverse effects. Therapeutic efficacy was monitored by histological mapping of the urinary bladder 8 weeks after treatment and at different time points thereafter. The study proved that intravesical instillation of the 213 Bi-immunoconjugate targeting EGFR is feasible. No adverse effects were observed and all blood and urine parameters determined remained in their normal ranges. Therapeutic efficacy was considered satisfactory, in that three of the 12 patients showed no signs of CIS 44, 30 and 3 months after treatment. Intravesical instillation of 213 Bi-anti-EGFR monoclonal antibody was well tolerated and showed therapeutic efficacy. Repeated instillation and/or instillation of higher activities of the 213 Bi-immunoconjugate might lead to better therapeutic outcomes. A phase I clinical trial is planned.

  13. 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 ...

  14. Prevention of carcinoma of cervix with human papillomavirus vaccine.

    Science.gov (United States)

    Gavarasana, S; Kalasapudi, R S; Rao, T D; Thirumala, S

    2000-01-01

    Carcinoma of cervix is the most common cancer found among the women of India. Though cervical cytology screening was effective in preventing carcinoma of cervix in developed nations, it is considered unsuitable in developing countries. Recent research has established an etiological link between human papillomavirus infection and carcinoma of cervix. In this review, an attempt is made to answer the question, 'whether carcinoma of cervix can be prevented with human papillomavirus vaccine?' Literature search using Pubmed and Medline was carried out and relevant articles were reviewed. There is ample experimental evidence to show that DNA of human papillomavirus integrates with cervical cell genome. Viral genes E6 and E7 of HPV type 16 and 18 inactivate p53 function and Rb gene, thus immortalize the cervical epithelial cells. Recombinant vaccines blocked the function of E6 and E7 genes preventing development of papillomas in animals. Vaccination with HPV-VLPs encoding for genes of E6 and E7 neutralizes HPV integrated genome of malignant cells of uterine cervix. Based on experimental evidence, it is possible to prevent carcinoma of cervix with human papillomavirus vaccine, Further research is necessary to identify a effective and safe HPV vaccine, routes of administration and characteristics of potential beneficiaries.

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

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    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.

  16. 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...

  17. CARCINOMA OF THE LARYNX AND HUMAN PAPILLOMA VIRUS INFECTION

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    Georgi N. Nikolov

    2016-03-01

    Full Text Available Background: Laryngeal carcinoma is one of the most common form of head and neck cancer. During the last two decades, it has been recognized that this cancer is causally related to human papillomavirus (HPV. Objective: We presented a study on prevalence of human papilloma viruses (HPV in patients with laryngeal carcinoma. Methods: This study consists of 43 patients with laryngeal carcinoma who were diagnosed and treated with surgical techniques in Department of Otorhinolaryngology, University Hospital, Pleven, Bulgaria. Immunohistochemistry of p16INK4a and Ki-67 were used to prove the relationship between high-risk-HPV (HR-HPV and carcinogenesis. Results: Papilloma virus infection with high-risk oncogenic types of HPV was determined in more than 39.5% of surgically treated patients with histologically proven laryngeal cancer. HPV-induced carcinogenesis was assumed in 17 (13.9% of all patients whose spouses were operated from cervical cancer. The patients with HPV-positive laryngeal carcinoma were younger than the others in the group (8 years on average. Risk factors for development of HPV-associated laryngeal carcinoma were related to higher number of sexual partners and the practice of oral sex. Frequently, in patients with HPV-associated laryngeal carcinoma we find data for so-called “family’s carcinogenesis”. The possibility of appearance (either preceding or following the treatment of a second carcinoma and/or tumour recurrence is higher in HPV-positive laryngeal carcinomas. Conclusion: It is recommended to extend the diagnostic methods for laryngeal and hypo pharyngeal cancer with a routine search for high-risk oncogenic HPV strains.

  18. Comparing Intra-Arterial Chemotherapy Combined With Intravesical Chemotherapy Versus Intravesical Chemotherapy Alone: A Randomised Prospective Pilot Study for T1G3 Bladder Transitional Cell Carcinoma After Bladder-Preserving Surgery

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Junxing, E-mail: Junxingchen@hotmail.com; Yao, Zhijun, E-mail: yaozhijun1985@qq.com; Qiu, Shaopeng, E-mail: qiushp@mail.sysu.edu.cn; Chen, Lingwu, E-mail: chenlingwu@hotmail.com [First Affiliated Hospital of Sun Yat-Sen University, Department of Urology (China); Wang, Yu, E-mail: zsyyjr@163.com; Yang, Jianyong, E-mail: yangjianyong_2011@163.com; Li, Jiaping, E-mail: jpli3s@126.com [First Affiliated Hospital of Sun Yat-Sen University, Department of Interventional Oncology (China)

    2013-12-15

    Purpose: To compare the efficacy of intra-arterial chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder transitional cell carcinoma (BTCC) followed by bladder-preserving surgery. Materials and Methods: Sixty patients with T1G3 BTCC were randomly divided into two groups. After bladder-preserving surgery, 29 patients (age 30-80 years, 24 male and 5 female) received intra-arterial chemotherapy in combination with intravesical chemotherapy (group A), whereas 31 patients (age 29-83 years, 26 male and 5 female) were treated with intravesical chemotherapy alone (group B). Twenty-nine patients were treated with intra-arterial epirubicin (50 mg/m{sup 2}) + cisplatin (60 mg/m{sup 2}) chemotherapy 2-3 weeks after bladder-preserving surgery once every 4-6 weeks. All of the patients received the same intravesical chemotherapy: An immediate prophylactic was administered in the first 6 h. After that, therapy was administered one time per week for 8 weeks and then one time per month for 8 months. The instillation drug was epirubicin (50 mg/m{sup 2}) and lasted for 30-40 min each time. The end points were tumour recurrence (stage Ta, T1), tumour progression (to T2 or greater), and disease-specific survival. During median follow-up of 22 months, the overall survival rate, tumour-specific death rate, recurrence rate, progression rate, time to first recurrence, and adverse reactions were compared between groups. Results: The recurrence rates were 10.3 % (3 of 29) in group A and 45.2 % (14 of 31) in group B, and the progression rates were 0 % (0 of 29) in group A and 22.6 % (7 of 31) in group B. There was a significant difference between the two groups regarding recurrence (p = 0.004) and progression rates (p = 0.011). Median times to first recurrence in the two groups were 15 and 6.5 months, respectively. The overall survival rates were 96.6 and 87.1 %, and the tumour-specific death rates were 0 % (0 of 29) and 13.5 % (4 of 31

  19. Patients with a negative cystoscopy and negative Nmp22® Bladderchek® test are at low risk of missed transitional cell carcinoma of the bladder: a prospective evaluation

    Directory of Open Access Journals (Sweden)

    John D. Terrell

    2011-12-01

    Full Text Available OBJECTIVES: Urine based tumor markers have uncertain utility in diagnosis or surveillance of patients with bladder cancer while cytology is commonly used. We evaluated whether cytology provides additional diagnostic information in patients with a negative NMP22® BladderChek® test (BladderChek and negative cystoscopy. MATERIALS AND METHODS: We performed subset analyses of 2 large prospective multi-center databases evaluating BladderChek for UCB detection and surveillance. These cohorts were analyzed for presence of cancer and result of urine cytology in setting of a negative cystoscopy and negative BladderChek. Subsequently, we prospectively performed cystoscopy, cytology and BladderChek on 434 patients at our institution being evaluated for UCB. RESULTS: In the detection database (n = 1331, 1065 patients had a negative cystoscopy and BladderChek. There were 3 cancers (stages Ta, Tis and T1 and cytology was atypical in one and reactive in two. In the surveillance cohort (n = 668 patients, 437 patients had negative cystoscopy and BladderChek. Cancer was found in 2 patients (stages Tis and Ta. The patient with Tis has dysplastic cytology and Ta tumor had reactive cytology. In our cohort of 434 patients, 288 pts had negative cystoscopy and BladderChek. One cancer was missed, a Ta ureteral urothelial carcinoma with a reactive cytology. CONCLUSIONS: In patients with negative cystoscopy and BladderChek, very few cancers are missed and cytology was not effective in detection. Use of a point-of-care test in conjunction with cystoscopy in lieu of cytology could decrease cost, provide immediate results, improve negative predictive value and reduce the uncertainty that results from inconclusive cytologic results.

  20. Progression of Intravesical Condyloma Acuminata to Locally Advanced Poorly Differentiated Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    A. Khambati

    2016-07-01

    Full Text Available Condyloma acuminata (CA is a common sexually transmitted disease caused by Human Papilloma Virus (HPV infection. CA of the bladder, however, is an exceedingly rare lesion. We present a rare case of poorly differentiated locally invasive squamous cell carcinoma (SCC arising from recurrent CA of the bladder in an immunocompetent patient and discuss pathophysiology and management of this unusual condition.

  1. Genomic instability in human actinic keratosis and squamous cell carcinoma

    Science.gov (United States)

    Cabral, Luciana Sanches; Neto, Cyro Festa; Sanches, José A; Ruiz, Itamar R G

    2011-01-01

    OBJECTIVE: To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation. INTRODUCTION: Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors. MATERIAL AND METHODS: Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers. RESULTS: MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III, one patient displayed three MSIs (D6S251, D6S252, and D9S180) and another patient exhibited an MSI (D9S280). The altered random amplified polymorphic DNA ranged from 70% actinic keratoses, 76% squamous cell carcinoma-I, and 90% squamous cell carcinoma-II, to 100% squamous cell carcinoma-III. DISCUSSION: The increased levels of alterations in the microsatellites, particularly in D6S251, and the random amplified polymorphic DNA fingerprints were statistically significant in squamous cell carcinomas, compared with actinic keratoses. CONCLUSION: The overall alterations that were observed in the repetitive DNA of actinic keratoses and

  2. 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

  3. 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.

  4. 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

  5. Primary Signet-Ring Cell Carcinoma of the Urinary Bladder Successfully Managed with Radical Cystectomy in a Young Patient

    Directory of Open Access Journals (Sweden)

    Farzad Allameh

    2017-01-01

    Full Text Available Primary signet-ring cell adenocarcinoma of bladder is a rare neoplasm, usually seen in middle age adults. We report the case of an 18-year-old man who presented with intermittent gross hematuria. Computed tomography imaging showed multifilling defects in the bladder. The patient underwent a transurethral resection of the bladder tumor. Histological findings were consistent with poorly differentiated mixed mucinous and signet-ring cell adenocarcinoma. We ruled out other possible origins of tumor by gastrointestinal endoscopy and colonoscopy. The patient was treated with radical cystectomy with prostate and seminal vesicle sparing technique and orthotopic diversion using “W” ileum pouch with pelvic lymphadenectomy to the bifurcation of the aorta was done. Six-month follow-up of patient showed normal conditions without metastatic spread or any recurrence.

  6. 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.

  7. Preferential radiosensitization of human prostatic carcinoma cells by mild hyperthermia

    International Nuclear Information System (INIS)

    Ryu, Samuel; Brown, Stephen L.; Kim, Sang-Hie; Khil, Mark S.; Kim, Jae Ho

    1996-01-01

    Purpose: Recent cell culture studies by us and others suggest that some human carcinoma cells are more sensitive to heat than are rodent cells following mild hyperthermia. In studying the cellular mechanism of enhanced thermosensitivity of human tumor cells to hyperthermia, prostatic carcinoma cells of human origin were found to be more sensitive to mild hyperthermia than other human cancer cells. The present study was designed to determine the magnitude of radiosensitization of human prostatic carcinoma cells by mild hyperthermia and to examine whether the thermal radiosensitization is related to the intrinsic thermosensitivity of cancer cells. Methods and Materials: Two human prostatic carcinoma cell lines (DU-145 and PC-3) and other carcinoma cells of human origin, in particular, colon (HT-29), breast (MCF-7), lung (A-549), and brain (U-251) were exposed to temperatures of 40-41 deg. C. Single acute dose rate radiation and fractionated radiation were combined with mild hyperthermia to determine thermal radiosensitization. The end point of the study was the colony-forming ability of single-plated cells. Results: DU-145 and PC-3 cells were found to be exceedingly thermosensitive to 41 deg. C for 24 h, relative to other cancer cell lines. Ninety percent of the prostatic cancer cells were killed by a 24 h heat exposure. Prostatic carcinoma cells exposed to a short duration of heating at 41 deg. C for 2 h resulted in a substantial enhancement of radiation-induced cytotoxicity. The thermal enhancement ratios (TERs) of single acute dose radiation following heat treatment 41 deg. C for 2 h were 2.0 in DU-145 cells and 1.4 in PC-3 cells. The TERs of fractionated irradiation combined with continuous heating at 40 deg. C were similarly in the range of 2.1 to 1.4 in prostate carcinoma cells. No significant radiosensitization was observed in MCF-7 and HT-29 cells under the same conditions. Conclusion: The present data suggest that a significant radiosensitization of

  8. 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.

  9. 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.

  10. CTP synthase forms the cytoophidium in human hepatocellular carcinoma.

    Science.gov (United States)

    Chang, Chia-Chun; Jeng, Yung-Ming; Peng, Min; Keppeke, Gerson Dierley; Sung, Li-Ying; Liu, Ji-Long

    2017-12-15

    CTP synthase (CTPS) can aggregate into an intracellular macrostructure, the cytoophidium, in various organisms including human cells. Previous studies have shown that assembly of human CTPS cytoophidia may be correlated with the cellular metabolic status, and is able to promote the activity of CTPS. A correlation between the cytoophidium and cancer metabolism has been proposed but not yet been revealed. In the current study we provide clear evidence of the presence of CTPS cytoophidia in various human cancers and some non-cancerous tissues. Moreover, among 203 tissue samples of hepatocellular carcinoma, 56 (28%) samples exhibited many cytoophidia, whereas no cytoophidia were detected in adjacent non-cancerous hepatocytes for all samples. Our findings suggest that the CTPS cytoophidium may participate in the adaptive metabolism of human hepatocellular carcinoma. Copyright © 2017. Published by Elsevier Inc.

  11. Expression of epidermal growth factor receptors in human endometrial carcinoma

    DEFF Research Database (Denmark)

    Nyholm, H C; Nielsen, Anette Lynge; Ottesen, B

    1993-01-01

    Little data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous...... hyperplasia. EGF-R was identified on frozen tissue sections by means of an indirect immunoperoxidase technique with a monoclonal antibody against the external domain of the EGF-R. Seventy-one percent of the carcinomas expressed positive EGF-R immunoreactivity. In general, staining was most prominent...

  12. Neoadjuvant chemotherapy with methotrexate and cisplatin prior to radiotherapy for invasive transitional cell carcinoma of the bladder. Assessment of feasibility and toxicity

    International Nuclear Information System (INIS)

    Howard, G.C.W.; Cornbleet, M.A.; Whillis, D.; Hargreave, T.B.; Chisholm, G.D.

    1991-01-01

    A prospective study has been performed to assess the feasibility and toxicity of administering neoadjuvant chemotherapy with methotrexate and cisplatin prior to radical radiotherapy. Twenty patients with advanced transitional cell carcinoma of the bladder were assessed after each of 3 courses of chemotherapy, after radiotherapy and 6 months following treatment. Of particular concern was whether neoadjuvant chemotherapy compromised the ability to give potentially curative radical radiotherapy, delayed effective palliation of distressing urinary symptoms, or allowed local tumour progression prior to definitive treatment. It was concluded that this chemotherapy regimen was well tolerated, did not compromise the ability to give radical radiotherapy and resulted in the prompt palliation of urinary symptoms. This treatment, however, did not stop the development or progression of metastatic disease in some patients. In only 1 patient was there local progression during chemotherapy. (author)

  13. The association of ABO blood type with disease recurrence and mortality among patients with urothelial carcinoma of the bladder undergoing radical cystectomy.

    Science.gov (United States)

    Gershman, Boris; Moreira, Daniel M; Tollefson, Matthew K; Frank, Igor; Cheville, John C; Thapa, Prabin; Tarrell, Robert F; Thompson, Robert Houston; Boorjian, Stephen A

    2016-01-01

    To evaluate the association of ABO blood type with clinicopathologic outcomes and mortality among patients with urothelial carcinoma of the bladder treated with radical cystectomy (RC). We identified 2,086 consecutive patients who underwent RC between 1980 and 2008. Postoperative recurrence-free survival (RFS) and cancer-specific survival (CSS) were estimated using the Kaplan Meier method and compared with the log-rank test. Cox proportional hazards regression models were used to evaluate the association of ABO blood type with outcomes. A total of 913 (44%), 881 (42%), 216 (10%), and 76 (4%) patients had blood type O, A, B, and AB, respectively. Median postoperative follow-up among survivors was 11.0 years (interquartile range: 7.7-15.9y). Overall, 1,561 patients died, with 770 deaths attributable to bladder cancer. Non-O blood type was associated with significantly worse 5-year RFS (65% vs. 69%; P = 0.04) and/or CSS (64% vs. 70%; P = 0.02). In particular, among patients with≤pT2N0 disease, the 5-year RFS for those with non-O vs. O blood type was 75% vs. 82%, respectively (P = 0.002), whereas the 5-year CSS was 77% vs. 85%, respectively (P = 0.001). Moreover, on multivariable analysis, blood type A remained independently associated with an increased risk of cancer-specific mortality (hazard ratio = 1.22; P = 0.01). Non-O blood type, particularly blood type A, is associated with a significantly increased risk of death from bladder cancer among patients undergoing RC. If validated, the utility of a multimodal therapy approach, including perioperative chemotherapy, or more frequent postoperative surveillance in this cohort warrants further study. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Knockdown of long non-coding RNA Taurine Up-Regulated 1 inhibited doxorubicin resistance of bladder urothelial carcinoma via Wnt/β-catenin pathway.

    Science.gov (United States)

    Xie, Dalong; Zhang, Hui; Hu, Xuanhao; Shang, Chao

    2017-10-24

    In genitourinary system, bladder cancer (BC) is the most common and lethal malignant tumor, which most common type is bladder urothelial carcinoma (BUC). Long non-coding RNA (lncRNA) Taurine Up-Regulated 1 (TUG1) gene is high-expressed in several malignant tumors, including BC. In this study, over-expression of TUG1 was found in BUC tissues and cell line resistant to doxorubicin (Dox). Knockdown of TUG1 inhibited the Dox resistance and promoted the cytotoxicity induced by Dox in T24/Dox cells. TUG1 knockdown also depressed the Wnt/β-catenin pathway, and the activation the Wnt/β-catenin pathway partly reversed the inhibitory effects of TUG1 knockdown on Dox resistance in T24/Dox cells. In conclusion, up-regulation of lncRNA TUG1 was related with the poor response of BUC patients to Dox chemotherapy, knockdown of TUG1 inhibited the Dox resistance of BUC cells via Wnt/β-catenin pathway. These findings might assist in the discovery of novel potential diagnostic and therapeutic target for BUC, thereby improve the effects of clinical treatment in patients.

  15. Seborrheic Keratoses as the First Sign of Bladder Carcinoma: Case Report of Leser-Trélat Sign in a Rare Association with Urinary Tract Cancer

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    Aline Stollmeier

    2016-01-01

    Full Text Available Introduction. Skin disorders can be the first manifestation of occult diseases. The recognition of typical paraneoplastic dermatoses may anticipate the cancer diagnosis and improve its prognosis. Although rarely observed, the sudden appearance and/or rapid increase in number and size of seborrheic keratoses can be associated with malignant neoplasms, known as the sign of Leser-Trélat. The aim of this report is to unveil a case of a patient whose recently erupted seborrheic keratoses led to investigation and consequent diagnosis of bladder cancer. Case Presentation. A 67-year-old man was admitted to the intensive care unit due to an exacerbation of chronic obstructive pulmonary disease (COPD. On physical examination, multiple seborrheic keratoses on the back of the hands, elbows, and trunk were observed; the patient had a 4-month history of these lesions yet was asymptomatic. The possibility of Leser-Trélat syndrome justified the investigation for neoplasia, and a bladder carcinoma was detected by CT-scan. The patient denied previous hematuria or any other related symptoms. Many of the lesions regressed during oncologic treatment. Conclusion. Despite the critics on the validity of the sign of Leser-Trélat, our patient fulfills the description of the disease, though urinary malignancy is a rare association. That corroborates the need of further investigation when there is a possibility of paraneoplastic manifestation.

  16. Expression of AR, 5αR1 and 5αR2 in bladder urothelial carcinoma and relationship to clinicopathological factors.

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    Hata, Shuko; Ise, Kazue; Azmahani, Abdullah; Konosu-Fukaya, Sachiko; McNamara, Keely May; Fujishima, Fumiyoshi; Shimada, Keiji; Mitsuzuka, Koji; Arai, Yoichi; Sasano, Hironobu; Nakamura, Yasuhiro

    2017-12-01

    Bladder urothelial carcinoma is increasing in incidence with age and its prognosis could become worse when accompanied with metastasis. Effective treatment of these advanced patients is required and it becomes important to understand its underlying biology of this neoplasm, especially with regard to its biological pathways. A potential proposed pathway is androgen receptor (AR)-mediated intracellular signaling but the details have remained relatively unexplored. The expression of AR, 5α-reductase type1 (5αR1) and 5α-reductase type2 (5αR2) were examined in the bladder cancer cell line T24 and surgical pathology specimens. We also evaluated the status of androgen related cell proliferation and migration using the potent, non-aromatizable androgen agonist 5α-dihydrotestosterone (DHT). DHT treatment significantly increased AR mRNA expression level, but not those of 5αR1 and 5αR2 in T24 cells. DHT also suppressed cellular migration with weaker and opposite effects on cell proliferation. A significant inverse correlation was detected between pT stage and AR, 5αR1 and 5αR2 immunoreactivity. Inverse correlations detected between tumor grade and AR/androgen metabolizing enzyme also suggested that the loss of AR and androgen-producing enzymes could be associated with tumor progression. Effects of DHT on cells also suggest that androgens may regulate cellular behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Insulin-like growth factor-1 receptor overexpression is associated with outcome in invasive urothelial carcinoma of urinary bladder: a retrospective study of patients treated using radical cystectomy.

    Science.gov (United States)

    Gonzalez-Roibon, Nilda; Kim, Jenny J; Faraj, Sheila F; Chaux, Alcides; Bezerra, Stephania M; Munari, Enrico; Ellis, Carla; Sharma, Rajni; Keizman, Daniel; Bivalacqua, Trinity J; Schoenberg, Mark; Eisenberger, Mario; Carducci, Michael; Netto, George J

    2014-06-01

    To assess the insulin-like growth factor-1 receptor (IGF1R) expression in urothelial carcinoma (UC) and its prognostic role in relation to clinicopathologic parameters. A total of 100 cases of invasive UC were evaluated using tissue microarrays. Membranous IGF1R staining was evaluated using immunohistochemistry. A scoring method analogous to that of HER2 expression in breast carcinoma was used, and the highest score was assigned in each tumor. IGF1R was considered overexpressed in cases with score≥1. We found IGF1R overexpression in 62% of invasive UC. IGF1R overexpression was associated with race (P=.04) and pT category (P=.03). Median follow-up was 29 months (range, 0.5-212). Progression rate was 60%, and overall mortality and cancer-specific mortality rates were 69% and 51%, respectively. In invasive UC, IGF1R overexpression was significantly associated with overall mortality and cancer-specific mortality (Mantel Cox P=.0002 and P=.006, respectively). IGF1R overexpression was associated with increased hazard ratios (HRs) for overall mortality (HR=2.63, P=.001) and cancer-specific mortality (HR=2.45, P=.01), independently and after adjusting for clinicopathologic features and treatment modalities. We found IGF1R overexpression in 62% of bladder UC. More importantly, IGF1R overexpression was a significant predictor of overall mortality and cancer-specific mortality, suggesting its potential role as a prognosticator in UC of bladder. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. 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 ...

  19. 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 ...

  20. Epidermal growth factor and its receptors in human pancreatic carcinoma

    International Nuclear Information System (INIS)

    Chen, Y.F.; Pan, G.Z.; Hou, X.; Liu, T.H.; Chen, J.; Yanaihara, C.; Yanaihara, N.

    1990-01-01

    The role of epidermal growth factor (EGF) in oncogenesis and progression of malignant tumors is a subject of vast interest. In this study, radioimmunoassay and radioreceptor assay of EGF were established. EGF contents in malignant and benign pancreatic tumors, in normal pancreas tissue, and in culture media of a human pancreatic carcinoma cell line were determined. EGF receptor binding studies were performed. It was shown that EGF contents in pancreatic carcinomas were significantly higher than those in normal pancreas or benign pancreatic tumors. EGF was also detected in the culture medium of a pancreatic carcinoma cell line. The binding of 125I-EGF to the pancreatic carcinoma cells was time and temperature dependent, reversible, competitive, and specific. Scatchard analysis showed that the dissociation constant of EGF receptor was 2.1 X 10(-9) M, number of binding sites was 1.3 X 10(5) cell. These results indicate that there is an over-expression of EGF/EGF receptors in pancreatic carcinomas, and that an autocrine regulatory mechanism may exist in the growth-promoting effect of EGF on tumor cells

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

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    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

  2. Dimethylarsinic acid in drinking water changed the morphology but not the expression of DNA repair genes of bladder transitional epithelium in F344 rats

    Science.gov (United States)

    Inorganic arsenic increases urinary bladder transitional cell carcinoma in humans. In laboratory animals, it is dimethylarsinic acid [DMA(V)], a major arsenic metabolite in the urine of inorganic arsenic-exposed people, that increases transitional cell carcinoma, namely in F344 r...

  3. 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.

  4. Induction of Human Squamous Cell-Type Carcinomas by Arsenic

    International Nuclear Information System (INIS)

    Martinez, V. D.; Becker-Santos, D. D.; Vucic, E. A.; Lam, S.; Lam, W. L.

    2011-01-01

    Arsenic is a potent human carcinogen. Around one hundred million people worldwide have potentially been exposed to this metalloid at concentrations considered unsafe. Exposure occurs generally through drinking water from natural geological sources, making it difficult to control this contamination. Arsenic biotransformation is suspected to have a role in arsenic-related health effects ranging from acute toxicities to development of malignancies associated with chronic exposure. It has been demonstrated that arsenic exhibits preference for induction of squamous cell carcinomas in the human, especially skin and lung cancer. Interestingly, keratins emerge as a relevant factor in this arsenic-related squamous cell-type preference. Additionally, both genomic and epi genomic alterations have been associated with arsenic-driven neoplastic process. Some of these aberrations, as well as changes in other factors such as keratins, could explain the association between arsenic and squamous cell carcinomas in humans.

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

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    Jonathan A Ewald

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

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

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    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.

  7. Impact of the Ki-67 labeling index and p53 expression status on disease-free survival in pT1 urothelial carcinoma of the bladder.

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    Vetterlein, Malte W; Roschinski, Julia; Gild, Philipp; Marks, Phillip; Soave, Armin; Doh, Ousman; Isbarn, Hendrik; Höppner, Wolfgang; Wagner, Walter; Shariat, Shahrokh F; Brausi, Maurizio; Büscheck, Franziska; Sauter, Guido; Fisch, Margit; Rink, Michael

    2017-12-01

    The identification of protein biomarkers to guide treatment decisions regarding adjuvant therapies for high-risk non-muscle-invasive bladder cancer (NMIBC) has been of increasing interest. Evidence of the impact of tumor suppressor gene product p53 and cell proliferation marker Ki-67 on oncologic outcomes in bladder cancer patients at highest risk of recurrence and progression is partially contradictory. We sought to mirror contemporary expression patterns of p53 and Ki-67 in a select cohort of patients with pT1 bladder cancer. Patients from four Northern German institutions with a primary diagnosis of pT1 bladder cancer between 2009 and 2016 and complete data regarding p53 or Ki-67 expression status were included for final analyses. Baseline patient characteristics (age, gender, age-adjusted Charlson comorbidity index) and tumor characteristics [diagnostic sequence, tumor focality, concomitant carcinoma in situ, 1973 World Health Organization (WHO) grading, lymphovascular invasion, adjuvant instillation therapy] were abstracted by retrospective chart review. Immunohistochemistry for detection of p53 and Ki-67 expression was performed according to standardized protocols. Microscopic analyses were performed by central pathologic review. First, we compared patients with positive vs. negative p53 expression and Ki-67 labeling index [>40% vs. ≤40%; cutoffs based on best discriminative ability in univariable Cox regression analysis with disease-free survival (DFS) as endpoint] with regard to baseline and tumor characteristics. Second, we evaluated the effect of biomarker positivity on DFS by plotting univariable Kaplan-Meier curves and performing uni- and multivariable Cox regression analyses. Of 102 patients with complete information on p53 status, 44 (43.1%) were p53 positive, and they more often harbored concomitant carcinoma in situ (50.0% vs. 27.6%; P=0.032) and 1973 WHO grade 3 (97.7% vs. 69.0%; P=0.001) compared to their p53 negative counterparts. Of 79

  8. 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

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

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    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

  10. 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

  11. The Impact of Multiple Malignancies on Patients with Bladder Carcinoma: A Population-Based Study Using the SEER Database

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    Joshua R. Ehrlich

    2009-01-01

    Results. Analyses demonstrated diminished survival among AB and ABS cohorts. However, when cohorts were substratified by stage, patients in the high-stage BS cohort appeared to have a survival advantage over high-stage BO patients. Conclusions. Bladder cancer patients with multiple malignancies have diminished survival. The survival advantage of high-stage BS patients is likely a statistical phenomenon. Such findings are important to shape future research and to improve our understanding of patients with multiple malignancies.

  12. Image-Guided Radiation Therapy for Muscle-Invasive Carcinoma of the Urinary Bladder with Cone Beam CT Scan: Use of Individualized Internal Target Volumes for a Single Patient

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    Gagan Saini

    2012-09-01

    Full Text Available Introduction: While planning radiation therapy (RT for a carcinoma of the urinary bladder (CaUB, the intra-fractional variation of the urinary bladder (UB volume due to filling-up needs to be accounted for. This internal target volume (ITV is obtained by adding internal margins (IM to the contoured bladder. This study was planned to propose a method of acquiring individualized ITVs for each patient and to verify their reproducibility. Methods: One patient with CaUB underwent simulation with the proposed ‘bladder protocol’. After immobilization, a planning CT scan on empty bladder was done. He was then given 300 ml of water to drink and the time (T was noted. Planning CT scans were performed after 20 min (T+20, 30 min (T+30 and 40 min (T+40. The CT scan at T+20 was co-registered with the T+30 and T+40 scans. The bladder volumes at 20, 30 and 40 min were then contoured as CTV20, CTV30 and CTV40 to obtain an individualized ITV for our patient. For daily treatment, he was instructed to drink water as above, and the time was noted; treatment was started after 20 min. Daily pre- and post-treatment cone beam CT (CBCT scans were done. The bladder visualized on the pre-treatment CBCT scan was compared with CTV20 and on the post-treatment CBCT scan with CTV30. Results: In total, there were 65 CBCT scans (36 pre- and 29 post-treatment. Individualized ITVs were found to be reproducible in 93.85% of all instances and fell outside in 4 instances. Conclusions: The proposed bladder protocol can yield a reproducible estimation of the ITV during treatment; this can obviate the need for taking standard IMs.

  13. Internal Iliac Artery Embolization for the Control of Severe Bladder Hemorrhage Secondary to Carcinoma: Long-Term Follow-Up

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    Ahmed El-Assmy

    2007-01-01

    Full Text Available The purpose of this study was to evaluate the efficacy and long-term complications of internal iliac artery embolization as a palliative measure in the control of intractable hemorrhage from advanced bladder malignancy. From January 1998 through December 2005, seven patients underwent transcatheter arterial embolization (TAE of anterior division of internal iliac artery bilaterally for intractable bladder hemorrhage. After embolization, patients were followed for the efficacy of the procedure in controlling hematuria and complications. TAE was successful in immediate control of severe hemorrhage in all seven patients after a mean period of 4 days. At a mean (range follow-up of 10 (6–12 months, the hemorrhage was permanently controlled in four (57% patients. Three patients developed hematuria and required emergency admissions; two had mild hematuria and were managed conservatively, and the remaining one required a second attempt of embolization after 2 months from the first one. During the whole period of follow-up, there were no significant complications related to embolization. Internal iliac artery embolization is an effective and minimally invasive option when managing advanced bladder malignancies presenting with intractable bleeding. The long-term follow-up showed control of bleeding in the majority of such patients with no serious complications.

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

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    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.

  15. Estramustine: A novel radiation enhancer in human carcinoma cells

    International Nuclear Information System (INIS)

    Ryu, S.; Gabel, M.; Khil, M.S.

    1994-01-01

    Estramustine (EM), an antimicrotubule agent, binds microtubule-associated proteins, causes spindle disassembly, and arrests cells at the late G 2 /M phase of the cell cycle. Since cells in the G 2 /M phase are the most radiosensitive and some human cancer cells contain high level of EM-binding protein, experiments were carried out to determine whether radiation sensitization could be obtained in human carcinoma cells. Cells containing a high level of EM-binding protein such as prostate carcinoma (DU-145), breast carcinoma (MCF-7), and malignant glioma (U-251) were used to demonstrate radiosensitization. Cervical carcinoma (HeLa-S 3 ) and colon carcinoma (HT-29) cells which are not known to contain EM-binding protein were also employed. Cell survival was assayed by the colony forming ability of single plated cells in culture to obtain dose-survival curves. Pretreatment of DU-145, MCF-7, and U-251 cells to a nontoxic concentration (5 μM) of EM for more than one cell cycle time, substantially enhanced the radiation-induced cytotoxicity. The sensitizer enhancement ratio of these cells ranged from 1.35-1.52. The magnitude of the enhancement was dependent on the drug concentration and exposure time. The rate of cell accumulation in G 2 /M phase, as determined by flow cytometry, increased with longer treatment time in the cell lines which showed radiosensitization. Other antimicrotubule agents such as taxol and vinblastine caused minimal or no radiosensitization at nontoxic concentrations. The data provide a radiobiological basis for using EM as a novel radiation enhancer, with the property of tissue selectivity. 29 refs., 4 figs., 1 tab

  16. Mechanism of cisplatin resistance in human urothelial carcinoma cells.

    Science.gov (United States)

    Yu, Hui-Min; Wang, Tsing-Cheng

    2012-05-01

    An isogenic pair of cisplatin-susceptible (NTUB1) and -resistant (NTUB1/P) human urothelial carcinoma cell lines was used to elucidate the mechanism of cisplatin resistance. The significantly lower intracellular platinum (IP) concentration, which resulted from the decreased cisplatin uptake, was found in NTUB1/P cells. The enhancement of IP concentration did not increase the susceptibility of NTUB1/P cells to cisplatin treatment. The reduction of IP concentration as well was unable to enhance the cisplatin-resistance in susceptible NTUB1 cells. This indicated that reduction of IP concentration was not the account for the development of cisplatin resistance here. Instead, the over expression of anti-apoptotic Bcl-2, anti-oxidative heme oxygenase-1 (HO-1) and cell cycle regulator p16INK4 seemed to be more important for the gaining of cisplatin in these human urothelial carcinoma cell. Copyright © 2012 Elsevier Ltd. All rights reserved.

  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. 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.

  19. 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...

  20. Deletion/duplication mutation screening of TP53 gene in patients with transitional cell carcinoma of urinary bladder using multiplex ligation-dependent probe amplification.

    Science.gov (United States)

    Bazrafshani, Mohammad Reza R; Nowshadi, Pouriaali A; Shirian, Sadegh; Daneshbod, Yahya; Nabipour, Fatemeh; Mokhtari, Maral; Hosseini, Fatemehsadat; Dehghan, Somayeh; Saeedzadeh, Abolfazl; Mosayebi, Ziba

    2016-02-01

    Bladder cancer is a molecular disease driven by the accumulation of genetic, epigenetic, and environmental factors. The aim of this study was to detect the deletions/duplication mutations in TP53 gene exons using multiplex ligation-dependent probe amplification (MLPA) method in the patients with transitional cell carcinoma (TCC). The achieved formalin-fixed paraffin-embedded tissues from 60 patients with TCC of bladder were screened for exonal deletions or duplications of every 12 TP53 gene exons using MLPA. The pathological sections were examined by three pathologists and categorized according to the WHO scoring guideline as 18 (30%) grade I, 22 (37%) grade II, 13 (22%) grade III, and 7 (11%) grade IV cases of TCC. None mutation changes of TP53 gene were detected in 24 (40%) of the patients. Furthermore, mutation changes including, 15 (25%) deletion, 17 (28%) duplication, and 4 (7%) both deletion and duplication cases were observed among 60 samples. From 12 exons of TP53 gene, exon 1 was more subjected to exonal deletion. Deletion of exon 1 of TP53 gene has occurred in 11 (35.4%) patients with TCC. In general, most mutations of TP53, either deletion or duplication, were found in exon 1, which was statistically significant. In addition, no relation between the TCC tumor grade and any type of mutation were observed in this research. MLPA is a simple and efficient method to analyze genomic deletions and duplications of all 12 exons of TP53 gene. The finding of this report that most of the mutations of TP53 occur in exon 1 is in contrast to that of the other reports suggesting that exons 5-8 are the most (frequently) mutated exons of TP53 gene. The mutations of exon 1 of TP53 gene may play an important role in the tumorogenesis of TCC. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  1. Elevated metallothionein-bound cadmium concentrations in urine from bladder carcinoma patients, investigated by size exclusion chromatography-inductively coupled plasma mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Wolf, Christian [Department of Molecular Trace Element Research in the Life Sciences, Helmholtz Centre Berlin for Materials and Energy, Glienicker Str. 100, 14109 Berlin (Germany)], E-mail: wolf@helmholtz-berlin.de; Strenziok, Romy [Department of Urology, Charite University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin (Germany); Kyriakopoulos, Antonios [Department of Molecular Trace Element Research in the Life Sciences, Helmholtz Centre Berlin for Materials and Energy, Glienicker Str. 100, 14109 Berlin (Germany)

    2009-01-12

    Cadmium is discussed as being involved in the development of transitional cell carcinoma (TCC) of the bladder and can be observed in urine of these patients. Investigations of urinary samples from bladder cancer patients and normal controls were carried out with special emphasis on metallothionein (MT)-bound cadmium. Compounds that are constituents of urine were separated in urine samples by means of size exclusion chromatography and cadmium was monitored continuously with a hyphenated inductively coupled plasma mass spectrometry (ICP-MS) system. MT-bound cadmium was quantified by peak area integration, taking into account the intensity of the rhodium signal which was added continuously before ICP-MS detection. The obtained results show that urinary cadmium is predominantly bound to the observed MT-fraction. The median of the MT-bound cadmium concentration in the control group was found to be 0.8 {mu}g L{sup -1} whereas the cancer group has a median of 1.8 {mu}g L{sup -1}. The variance of the data in the cancer group is much higher than in the controls. However, the urinary MT-bound cadmium is significantly elevated in the cancer group; odds-ratio test: 7.11 (95% C.I.: 1.89-26.80), taking into account the total protein content. Due to the fact that only one main cadmium-containing fraction was observed, there is no necessity to separate the MT-fraction before cadmium determination in urine samples in future studies.

  2. 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.

  3. Temporal morphologic changes in human colorectal carcinomas following xenografting.

    Science.gov (United States)

    Barkla, D H; Tutton, P J

    1983-03-01

    The temporal morphologic changes of human colorectal carcinomas following xenografting into immunosuppressed mice were investigated by the use of light and transmission electron microscopy. The results show that colorectal carcinomas undergo a series of morphologic changes during the initial 30-day period following transplantation. During the initial 1-5-day period the majority of tumor cells die, and during the following 5-10-day period the necrotic debris created during the 1-5-day period is removed by host-supplied inflammatory cells. Only small groups of peripherally placed tumor cells survived at the end of the first 10 days. During the 10-20-day period the tumor cell populations of xenografts were reestablished by a morphologically heterogeneous population of tumor cells, and during the 20-30 day period consolidation of this process continued and some xenografts showed macroscopic evidence of growth. The authors hypothesize that human colorectal carcinomas, like the antecedent epithelium, contain subpopulations of undifferentiated cells that give rise to populations of more-differentiated cells.

  4. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    Science.gov (United States)

    Barkla, D H; Whitehead, R H; Foster, H; Tutton, P J

    1988-09-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting from the apical surface. The microvilli are attached by a core of long microfilaments passing deep into the apical cytoplasm. Between the microvilli are parallel arrays of vesicles (caveoli) containing flocculent material. Two different but not mutually exclusive explanations for the presence of tuft cells are proposed. The first explanation is that tuft cells came from the resected tumour and have survived by mitotic division during subsequent passages. The second explanation suggests that tuft cells are the progeny of undifferentiated tumour cells. Descriptions of tuft cells in colon carcinomas are uncommon and possible reasons for this are presented. The morphology of tuft cells is consistent with that of a highly differentiated cell specialised for absorption, and these new models provide an opportunity to further investigate the structure and function of tuft cells.

  5. Human Papilloma Virus and Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Hayedeh Haeri

    2013-04-01

    Full Text Available Human papilloma virus (HPV has been suggested as an etiology of esophageal squamous cell carcinoma (SCC. The aim of this study was to investigate the prevalence of HPV infection in esophageal SCCs in our region with strict contamination control to prevent false positive results. Thirty cases of esophageal squamous cell carcinomas were chosen by simple random selection in a period of two years. PCR for target sequence of HPV L1 gene was performed on nucleic acid extracted from samples by means of GP5+/GP6+ primers. All tissue samples in both case and control groups were negative for HPV-DNA. Although the number of cases in this study was limited, the contribution of HPV in substantial number of esophageal SCCs in our region is unlikely.

  6. Human papilloma virus and esophageal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Hayedeh Haeri

    2014-03-01

    Full Text Available Human papillomavirus (HPV has also been suggested as an etiology of esophageal squamous cell carcinoma (SCC. The aim of this study was to investigate the prevalence of HPV infection in esophageal SCCs in our region with strict contamination control to prevent false positive results. Thirty cases of esophageal squamous cell carcinomas were chosen by simple random selection in a period of two years. PCR for target sequence of HPV L1 gene was performed on nucleic acid extracted from samples by means of GP5+/GP6+ primers. All tissue samples in both case and control groups were negative for HPV-DNA. Although the number of cases in this study was limited, the contribution of HPV in the substantial number of esophageal SCCs in our region is unlikely.

  7. 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

  8. 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

  9. 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.

  10. Plasma membrane proteomics of human embryonic stem cells and human embryonal carcinoma cells.

    NARCIS (Netherlands)

    Dormeyer, W.; van Hoof, D.; Braam, S.R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

    2008-01-01

    Human embryonic stem cells (hESCs) are of immense interest in regenerative medicine as they can self-renew indefinitely and can give rise to any adult cell type. Human embryonal carcinoma cells (hECCs) are the malignant counterparts of hESCs found in testis tumors. hESCs that have acquired

  11. [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.

  12. 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

  13. 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

  14. Ethacrynic acid: a novel radiation enhancer in human carcinoma cells

    International Nuclear Information System (INIS)

    Khil, Mark S.; Sang, Hie Kim; Pinto, John T.; Jae, Ho Kim

    1996-01-01

    Purpose: Because agents that interfere with thiol metabolism and glutathione S-transferase (GST) functions have been shown to enhance antitumor effects of alkylating agents in vitro and in vivo, the present study was conceived on the basis that an inhibitor of GST would enhance the radiation response of some selected human carcinoma cells. Ethacrynic acid (EA) was chosen for the study because it is an effective inhibitor of GST and is a well known diuretic in humans. Methods and Materials: Experiments were carried out with well-established human tumor cells in culture growing in Eagle's minimum essential medium (MEM) supplemented with 10% fetal calf serum (FCS). Cell lines used were MCF-7, MCF-7 adriamycin resistant (AR) cells (breast carcinoma), HT-29 cells (colon carcinoma), DU-145 cells (prostate carcinoma), and U-373 cells (malignant glioma). Cell survival following the exposure of cells to drug alone, radiation alone, and a combined treatment was assayed by determining the colony-forming ability of single plated cells in culture to obtain dose-survival curves. The drug enhancement ratio was correlated with levels of GST. Results: The cytotoxicity of EA was most pronounced in MCF-7, U-373, and DU-145 cells compared to MCF-7 AR and HT-29 cells. The levels of GST activity were found to be lower in those EA-sensitive cells. A significant radiation enhancement was obtained with EA-sensitive cells exposed to nontoxic concentrations of the drug immediately before or after irradiation. The sensitizer enhancement ratio (SER) of MCF-7 cells was 1.55 with EA (20 μg/ml), while the SER of MCF-7 AR was less than 1.1. Based on five different human tumor cells, a clear inverse relationship was demonstrated between the magnitude of SER and GST levels of tumor cells prior to the combined treatment. Conclusion: The present results suggest that EA, which acts as both a reversible and irreversible inhibitor of GST activity, could significantly enhance the radiation response of

  15. uPAR Expression Pattern in Patients with Urothelial Carcinoma of the Bladder--Possible Clinical Implications.

    Directory of Open Access Journals (Sweden)

    Line Hammer Dohn

    Full Text Available The objective of the present study was to confirm the expression and localisation pattern of the urokinase-type plasminogen activator receptor (uPAR focusing on its possible clinical relevance in patients with urothelial neoplasia of the bladder. uPAR is a central molecule in tissue remodelling during cancer invasion and metastasis and is an established prognostic marker in various cancer diseases other than bladder cancer. Formalin-fixed and paraffin-embedded tumour-tissue blocks from 186 patients treated with radical cystectomy were analysed. uPAR expression was scored as either negative or positive as well as by the actual score. Separate scores were obtained for cancer cells, macrophages and myofibroblasts at the invasive front and in tumour core. We were able to confirm, in an independent patient cohort, the tissue expression and localisation pattern of uPAR as investigated by Immunohistochemistry as well as a significant association between uPAR positivity and increasing tumour stage and tumour grade. This demonstrates the robustness of our previous and current findings. In addition the association between uPAR positive myofibroblasts and poor survival was reproduced. The highest hazard ratios for survival were seen for uPAR positive myofibroblasts both at the invasive front and in tumour core. Evaluating uPAR expression by the actual score showed a significant association between uPAR positive myofibroblasts in tumour core and an increased risk of cancer specific mortality. Our investigations have generated new and valuable biological information about the cell types being involved in tumour invasion and progression through the plasminogen activation system.

  16. 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.

  17. Use of Ulex europaeus agglutinin I (UEAI) to distinguish vascular and "pseudovascular" invasion in transitional cell carcinoma of bladder with lamina propria invasion.

    Science.gov (United States)

    Larsen, M P; Steinberg, G D; Brendler, C B; Epstein, J I

    1990-01-01

    We used Ulex europaeus agglutinin I (UEAI)-immunoperoxidase staining of endothelium to study the accuracy of hematoxylin and eosin (H&E) diagnosis, occurrence, and significance of lymphvascular invasion in transitional cell carcinoma (TCC) of the bladder invading the lamina propria (Stage T1). Original histologic slides from cases (1967 to 1985) with and without vascular invasion were destained and restained with UEAI-immunoperoxidase. Only 5 of 36 biopsies originally diagnosed with lymphvascular invasion had tumor nests within endothelium-lined spaces. The 31 negative biopsies had extensive retraction artifacts lined by connective tissue and fibroblasts around tumor nests. Thirty-five control biopsies remained negative for lymphvascular invasion. Clinical follow-up of the five patients with proven lymphvascular invasion found three without progression of disease 3 to 10 yr postbiopsy, one dead of a local recurrence of TCC 1.67 yr postbiopsy, and one lost to follow-up. Based on this study, we feel that lymphvascular invasion by TCC in Stage T1 tumors is unusual, is frequently misdiagnosed on H&E stain, and does not necessarily portend a poor prognosis.

  18. Efficacy of voided urinary cytology and ultrasonography compared to cystoscopy in the detection of urinary bladder cancer

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    N. Kumar

    2017-09-01

    Conclusions: Voided urinary cytology can be omitted as a screening test. Ultrasonography can be recommended as the initial imaging investigation for detection of bladder carcinoma in patients presenting with hematuria and for follow up of bladder carcinoma patients.

  19. LAT1 acts as a crucial transporter of amino acids in human thymic carcinoma cells

    Directory of Open Access Journals (Sweden)

    Keitaro Hayashi

    2016-11-01

    Full Text Available L-type amino acid transporter 1 (LAT1, SLC7A5 incorporates essential amino acids into cells. Recent studies have shown that LAT1 is a predominant transporter in various human cancers. However, the function of LAT1 in thymic carcinoma remains unknown. Here we demonstrate that LAT1 is a critical transporter for human thymic carcinoma cells. LAT1 was strongly expressed in human thymic carcinoma tissues. LAT1-specific inhibitor significantly suppressed leucine uptake and growth of Ty82 human thymic carcinoma cell lines, suggesting that thymic carcinoma takes advantage of LAT1 as a quality transporter and that LAT1-specific inhibitor might be clinically beneficial in therapy for thymic carcinoma.

  20. 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

  1. 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.

  2. Primary combined carcinoid and adenocarcinoma of the ileum associated with transitional carcinoma of the bladder. Single case report Causa infrecuente de disfagia en el postoperatorio tardío de la cirugía de la hernia de hiato

    Directory of Open Access Journals (Sweden)

    I. D. Venizelos

    2007-03-01

    Full Text Available Composite neoplasms, carcinoid and adenocarcinoma have been reported to occur in several parts of the body, including the stomach, ampulla of Vater, large bowel, lung, and urinary bladder. Here we report a case of a 74-year-old male with a composite carcinoid-adenocarcinoma of the ileum associated with a transitional cell carcinoma of the bladder. The microscopical examination of the composite tumor showed an admixture of typical carcinoid tumor and moderately a differentiated adenocarcinoma. Immunohistochemically, the two components showed clear-cut differentiations. A review of the literature revealed that this is the first reported case of composite carcinoid-adenocarcinoma of the ileum associated with transitional cell carcinoma of the urinary bladder.Las neoplasias compuestas, el carcinoide y el adenocarcinoma se ha observado que aparecen en varias partes del organismo, como el estómago, la ampolla de Vater, el intestino grueso, el pulmón y la vejiga urinaria. Publicamos aquí el caso de un varón de 74 años con un tumor compuesto de tipo carcinoide-adenocarcinoma del íleon asociado a un carcinoma vesical de células transicionales. El examen macroscópico del tumor compuesto mostró una mezcla de tumor carcinoide típico y adenocarcinoma moderadamente diferenciado. Desde el punto de vista inmunohistoquímico, los dos componentes estaban claramente diferenciados. Una revisión de la bibliografía reveló que este es el primer caso que se publica de un tumor compuesto de tipo carcinoide-adenocarcinoma del íleon asociado a un carcinoma de células transicionales de la vejiga urinaria.

  3. Implication of androgen receptor in urinary bladder cancer: a critical mini review

    OpenAIRE

    Rahmani, Arshad H; Alzohairy, Mohammad; Babiker, Ali Yousif Y; Khan, Amjad A; Aly, Salah M; Rizvi, Moshahid A

    2013-01-01

    Cancer is probably the most dreaded disease of mankind and the bladder cancer is the fifth most common type of cancer worldwide. It is a major cause of cancer morbidity and mortality. From amongst the bladder cancer, the Transitional Cell Carcinoma (TCC) is the most prevalent cancer of the bladder and accounts for 90% of all bladder cancer cases. Despite such a high prevalence, the molecular mechanism involved in the induction of bladder carcinoma and its progression are poorly understood. Tu...

  4. 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.

  5. 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.

  6. Carcinoma-specific Ulex europaeus agglutinin-I binding glycoproteins of human colorectal carcinoma and its relation to carcinoembryonic antigen.

    Science.gov (United States)

    Matsushita, Y; Yonezawa, S; Nakamura, T; Shimizu, S; Ozawa, M; Muramatsu, T; Sato, E

    1985-08-01

    Glycoproteins binding to Ulex europaeus agglutinin-I (UEA-I) lectin, which recognizes the terminal alpha-L-fucose residue, were analyzed in 18 cases of human colorectal carcinoma by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by the Western blotting method. In the distal large bowel (descending and sigmoid colon and rectum), high-molecular-weight glycoproteins binding to UEA-I existed in carcinoma tissue but not in normal mucosa. In the proximal large bowel (ascending and transverse colon), high-molecular-weight glycoproteins binding to UEA-I were found both in normal mucosa and in carcinoma tissue, whereas those from the carcinoma tissue had an apparently lower molecular weight as compared to the weight of those from the normal mucosa. Thus there is a biochemical difference in UEA-I binding glycoproteins between the normal mucosa and the carcinoma tissue, although in our previous histochemical study no difference was observed in UEA-I binding glycoproteins of the proximal large bowel between the carcinoma tissue and the normal mucosa. Furthermore, carcinoembryonic antigen from the carcinoma tissue was found to have the same electrophoretical mobility as the UEA-I binding glycoproteins.

  7. Fatty acid binding proteins (FABPs) in prostate, bladder and kidney cancer cell lines and the use of IL-FABP as survival predictor in patients with renal cell carcinoma

    International Nuclear Information System (INIS)

    Tölle, Angelika; Suhail, Saba; Jung, Monika; Jung, Klaus; Stephan, Carsten

    2011-01-01

    Fatty acid binding proteins (FABP) play an important role in carcinogenesis. Modified FABP expression patterns were described for prostate, bladder and for renal cell carcinoma. Studies on metabolic relationships and interactions in permanent cell lines allow a deeper insight into molecular processes. The aim of this study is therefore a systematic overview on mRNA and protein expressions of seven FABPs in frequently used urological cell lines. Nine cell lines of renal carcinomas, seven of urinary bladder carcinomas, and five of prostate carcinomas were investigated. Quantitative RT-qPCR and western blotting were used to determine different FABPs. In addition, 46 paired cancerous and noncancerous tissue samples from nephrectomy specimen with renal cell carcinomas were investigated regarding the ileum FABP mRNA expression level and associated with survival outcome. General characteristics of all urological carcinoma cell lines were the expression of E-and IL-FABP on mRNA and protein level, while the expressions differed between the cell lines. The protein expression was not always congruent with the mRNA expression. Renal cell carcinoma cell lines showed expressions of L-, H- and B-FABP mRNA in addition to the general FABP expression in five out of the eight investigated cell lines. In bladder cancer cell lines, we additionally found the expression of A-FABP mRNA in six cell lines, while H-FABP was present only in three cell lines. In prostate cancer cell lines, a strong reduction of A- and E- FABP mRNA was observed. The expression of B-FABP mRNA and protein was observed only in the 22 RV-1 cells. IL-FABP mRNA was over-expressed in renal tumour tissue. The IL-FABP ratio was identified as an independent indicator of survival outcome. Distinctly different FABP expression patterns were observed not only between the cell lines derived from the three cancer types, but also between the cell lines from the same cancer. The FABP patterns in the cell lines do not always

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. Apoptosis, proliferation and p53, cyclin D1, and retinoblastoma gene expression in relation to radiation response in transitional cell carcinoma of the bladder

    International Nuclear Information System (INIS)

    Moonen, Luc; Ong, Francisca; Gallee, Maarten; Verheij, Marcel; Horenblas, Simon; Hart, Augustinus A.M.; Bartelink, Harry

    2001-01-01

    Purpose: To determine whether the apoptotic index, the Ki67 index, and the expression of the p53, cyclin D1, and retinoblastoma genes correlate with local control, overall survival, and time to distant metastases in invasive bladder cancer treated with external beam radiation. Methods and Materials: Paraffin-embedded pretreatment biopsies from 83 patients with invasive transitional cell carcinoma of the bladder were scored morphologically for apoptosis and immunohistochemically for Ki67, p53, cyclin D1, and retinoblastoma gene expression. Survival analysis methods were used to assess overall survival, local control, and freedom from distant metastases. A multiple proportional hazard (PH) regression analysis was performed to study the prognostic value of the above mentioned biologic parameters (all divided into two categories, except Ki67) in addition to classical prognostic factors such as T stage, histologic grade, multifocality of the tumor, and completeness of transurethral resection. All patients were treated with external beam radiation as sole treatment. Median follow-up for the 19 patients still living was 7.5 years. Results: Apoptotic index varied from 0% to 3.4% with a mean of 0.8% and a median of 0.6%. Ki67 index varied from 0% to 60% with a mean of 14% and a median of 12%. P53 protein was detectable in 61% of the tumors. Overexpression of cyclin D1 was observed in 39% of the tumors and loss of retinoblastoma protein in 23% of the tumors. High Ki67 index was found to be significantly associated with p53 expression (p=0.04) and cyclin D1 overexpression (p=0.023). Cyclin D1 overexpression was found more often in Rb-positive tumors than in Rb-negative tumors (p=0.006). Other associations between the markers are less clear. Biologic markers were not correlated with T stage or grade. In the PH analysis local control was found to be significantly better for tumors with wild-type p53 (p=0.028). Also, tumors with an apoptotic index above the median value (0

  13. Photoaffinity labeling of the progesterone receptor from human endometrial carcinoma

    International Nuclear Information System (INIS)

    Clarke, C.L.; Satyaswaroop, P.G.

    1985-01-01

    A nude mouse model for the growth of human endometrial carcinoma and hormonal modulation of the progesterone receptor (PR) was established previously. This study describes the effect of 17 beta-estradiol and tamoxifen (TAM) on growth rate and PR concentration in a hormonally responsive human endometrial tumor (EnCa 101) grown in this experimental system and presents the first characterization of human endometrial carcinoma PR. EnCa 101 was transplanted subcutaneously into ovariectomized, BALB/c, nu/nu athymic mice and grown under 17 beta-estradiol-stimulated, TAM-stimulated, and control conditions. Both 17 beta-estradiol and TAM increased the growth rate of EnCa 101 in nude mice, and a parallel increase in the cytosol PR concentration was observed. PR was partially purified by phosphocellulose and DEAE cellulose chromatography, and the DEAE eluate was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and photoaffinity labeling with [17 alpha-methyl- 3 H]promegestone ([ 3 H]R5020). Two PR-negative tumors (EnCa K and EnCa V) were also examined in parallel. Photolabeling and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of EnCa 101 grown in the presence of 17 beta-estradiol or TAM revealed incorporation of [3H]R5020 into proteins of molecular weight approximately 116,000 and 85,000. Labeled proteins of molecular weight 66,000, 45,000, and 35,000 were also observed. No incorporation of [ 3 H]R5020 was observed in EnCa 101 grown in the absence of estrogen, nor was any observed in EnCa K or EnCa V

  14. Expression profiling of human renal carcinomas with functional taxonomic analysis

    Science.gov (United States)

    2002-01-01

    Background Molecular characterization has contributed to the understanding of the inception, progression, treatment and prognosis of cancer. Nucleic acid array-based technologies extend molecular characterization of tumors to thousands of gene products. To effectively discriminate between tumor sub-types, reliable laboratory techniques and analytic methods are required. Results We derived mRNA expression profiles from 21 human tissue samples (eight normal kidneys and 13 kidney tumors) and two pooled samples using the Affymetrix GeneChip platform. A panel of ten clustering algorithms combined with four data pre-processing methods identified a consensus cluster dendrogram in 18 of 40 analyses and of these 16 used a logarithmic transformation. Within the consensus dendrogram the expression profiles of the samples grouped according to tissue type; clear cell and chromophobe carcinomas displayed distinctly different gene expression patterns. By using a rigorous statistical selection based method we identified 355 genes that showed significant (p Matrix Organization and Adhesion. Conclusions Affymetrix GeneChip profiling differentiated clear cell and chromophobe carcinomas from one another and from normal kidney cortex. Clustering methods that used logarithmic transformation of data sets produced dendrograms consistent with the sample biology. Functional taxonomy provided a practical approach to the interpretation of gene expression data. PMID:12356337

  15. Expression profiling of human renal carcinomas with functional taxonomic analysis

    Directory of Open Access Journals (Sweden)

    Madore Steven J

    2002-09-01

    Full Text Available Abstract Background Molecular characterization has contributed to the understanding of the inception, progression, treatment and prognosis of cancer. Nucleic acid array-based technologies extend molecular characterization of tumors to thousands of gene products. To effectively discriminate between tumor sub-types, reliable laboratory techniques and analytic methods are required. Results We derived mRNA expression profiles from 21 human tissue samples (eight normal kidneys and 13 kidney tumors and two pooled samples using the Affymetrix GeneChip platform. A panel of ten clustering algorithms combined with four data pre-processing methods identified a consensus cluster dendrogram in 18 of 40 analyses and of these 16 used a logarithmic transformation. Within the consensus dendrogram the expression profiles of the samples grouped according to tissue type; clear cell and chromophobe carcinomas displayed distinctly different gene expression patterns. By using a rigorous statistical selection based method we identified 355 genes that showed significant (p Conclusions Affymetrix GeneChip profiling differentiated clear cell and chromophobe carcinomas from one another and from normal kidney cortex. Clustering methods that used logarithmic transformation of data sets produced dendrograms consistent with the sample biology. Functional taxonomy provided a practical approach to the interpretation of gene expression data.

  16. Lymphovascular invasion, ureteral reimplantation and prior history of urothelial carcinoma are associated with poor prognosis after partial cystectomy for muscle-invasive bladder cancer with negative pelvic lymph nodes.

    Science.gov (United States)

    Ma, B; Li, H; Zhang, C; Yang, K; Qiao, B; Zhang, Z; Xu, Y

    2013-10-01

    To identify predictive factors underlying recurrence and survival after partial cystectomy for pelvic lymph node-negative muscle-invasive bladder cancer (MIBC) (urothelial carcinoma) and to report the results of partial cystectomy among select patients. We retrospectively reviewed 101 cases that received partial cystectomy for MIBC (pT2-3N0M0) between 2000 and 2010. The log-rank test and a Cox regression analyses were performed to identify factors that were predictive of recurrence and survival. With a median follow-up of 53.0 months (range 9-120), the 5-year overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) rates were 58%, 65% and 50%, respectively. A total of 33 patients died of bladder cancer and 52 patients survived with intact bladder. Of the 101 patients included, 55 had no recurrence, 12 had non-muscle-invasive recurrence in the bladder that was treated successfully, and 34 had recurrence with advanced disease. The multivariate analysis showed that prior history of urothelial carcinoma (PH.UC) was associated with both CSS and RFS and weakly associated with OS; lymphovascular invasion (LVI) and ureteral reimplantation (UR) were associated with OS, CSS and RFS. Among patients with pelvic lymph node-negative MIBC, PH.UC and UR should be considered as contraindications for partial cystectomy, and LVI is predictive of poor outcomes after partial cystectomy. Highly selective partial cystectomy is a rational alternative to radical cystectomy for the treatment of MIBC with negative pelvic lymph nodes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Gender-specific differences in cancer-specific survival after radical cystectomy for patients with urothelial carcinoma of the urinary bladder in pathologic tumor stage T4a.

    Science.gov (United States)

    May, Matthias; Bastian, Patrick J; Brookman-May, Sabine; Fritsche, Hans-Martin; Tilki, Derya; Otto, Wolfgang; Bolenz, Christian; Gilfrich, Christian; Trojan, Lutz; Herrmann, Edwin; Moritz, Rudolf; Tiemann, Arne; Müller, Stefan C; Ellinger, Jörg; Buchner, Alexander; Stief, Christian G; Wieland, Wolf F; Höfner, Thomas; Hohenfellner, Markus; Haferkamp, Axel; Roigas, Jan; Zacharias, Mario; Nuhn, Philipp; Burger, Maximilian

    2013-10-01

    Bladder cancer (UCB) staged pT4a show heterogeneous outcome after radical cystectomy (RC). No risk model has been established to date. Despite gender-specific differences, no comparative studies exist for this tumor stage. Cancer-specific survival (CSS) of 245 UCB patients without neoadjuvant chemotherapy staged pT4a, pN0-2, M0 after RC were analyzed in a retrospective multi-center study. Seventeen patients were excluded from further analysis due to carcinoma in situ (CIS) of the prostatic urethra and/or positive surgical margins. Average follow-up period was 30 months (IQR: 14-45). The influence of different clinical and histopathologic variables on CSS was determined through uni- and multivariate Cox regression analyses. Two risk groups were generated using factors with independent effect in multivariate models. Internal validity of the prediction model was evaluated by bootstrapping. Eighty-four percent of the patients (n = 192) were male; 72% (n = 165) showed lymphovascular invasion (LVI). The 5-year CSS rate was 31%, and significantly different between male and female (35% vs. 15%, P = 0.003). Multivariate Cox regression modeling, female gender (HR = 1.83, P = 0.008), LVI (HR = 1.92, P = 0.005), and absence of adjuvant chemotherapy (HR = 0.61, P = 0.020) significantly worsened CSS. Two risk groups were generated using these 3 criteria, which differed significantly between each other in CSS (5-year-CSS: 46% vs. 12%, P < 0.001). The c-index value of the risk model was 0.61 (95% CI: 0.53-0.68, P < 0.001). Prognosis in UCB staged pT4a is heterogeneous. Female gender and LVI are adverse factors. Adjuvant chemotherapy seems to improve outcome. The present analysis establishes the first risk model for this demanding tumor stage. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. 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

  19. Neurogenic Bladder

    Directory of Open Access Journals (Sweden)

    Peter T. Dorsher

    2012-01-01

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

  20. Bladder 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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. Gastrin-releasing peptide receptor imaging in human breast carcinoma versus immunohistochemistry

    NARCIS (Netherlands)

    de Wiele, Christophe Van; Phonteyne, Philippe; Pauwels, Patrick; Goethals, Ingeborg; Van den Broecke, Rudi; Cocquyt, Veronique; Dierckx, Rudi Andre

    This study reports on the uptake of (99m)Tc-RP527 by human breast carcinoma and its relationship to gastrin-releasing peptide receptor (GRIP-R) expression as measured by immunohistochemistry (IHC). Methods: Nine patients referred because of a clinical diagnosis suggestive of breast carcinoma and 5

  9. 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.

  10. microRNA-145 promotes differentiation in human urothelial carcinoma through down-regulation of syndecan-1

    International Nuclear Information System (INIS)

    Fujii, Tomomi; Shimada, Keiji; Tatsumi, Yoshihiro; Hatakeyama, Kinta; Obayashi, Chiho; Fujimoto, Kiyohide; Konishi, Noboru

    2015-01-01

    A new molecular marker of carcinoma in the urinary bladder is needed as a diagnostic tool or as a therapeutic target. Potential markers include microRNAs (miRNAs), which are short, low molecular weight RNAs 19–24 nt long that regulate genes associated with cell proliferation, differentiation, and development in various cancers. In this study, we investigated the molecular mechanisms by which miR-145 promotes survival of urothelial carcinoma cells and differentiation into multiple lineages. We found miR-145 to regulate expression of syndecan-1, a heparin sulfate proteoglycan. Cell proliferation in the human urothelial carcinoma cell lines T24 and KU7 was assessed by MTS assay. Cellular senescence and apoptosis were measured by senescence-associated β-galactosidase (SA-β-gal) and TUNEL assay, respectively. Quantitative RT-PCR was used to measure mRNA expression of various genes, including syndecan-1, stem cell factors, and markers of differentiation into squamous, glandular, or neuroendocrine cells. Overexpression of miR-145 induced cell senescence, and thus significantly inhibited cell proliferation in T24 and KU7 cells. Syndecan-1 expression diminished, whereas stem cell markers such as SOX2, NANOG, OCT4, and E2F3 increased. miR-145 also up-regulated markers of differentiation into squamous (p63, TP63, and CK5), glandular (MUC-1, MUC-2, and MUC-5 AC), and neuroendocrine cells (NSE and UCHL-1). Finally, expression of miR-145 was down-regulated in high-grade urothelial carcinomas, but not in low-grade tumors. Results indicate that miR-145 suppresses syndecan-1 and, by this mechanism, up-regulates stem cell factors and induces cell senescence and differentiation. We propose that miR-145 may confer stem cell-like properties on urothelial carcinoma cells and thus facilitate differentiation into multiple cell types. The online version of this article (doi:10.1186/s12885-015-1846-0) contains supplementary material, which is available to authorized users

  11. 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.

  12. Human papillomavirus-mediated carcinogenesis and HPV-associated oral and oropharyngeal squamous cell carcinoma. Part 2: Human papillomavirus associated oral and oropharyngeal squamous cell carcinoma

    Science.gov (United States)

    2010-01-01

    Human papillomavirus (HPV) infection of the mouth and oropharynx can be acquired by a variety of sexual and social forms of transmission. HPV-16 genotype is present in many oral and oropharyngeal squamous cell carcinomata. It has an essential aetiologic role in the development of oropharyngeal squamous cell carcinoma in a subset of subjects who are typically younger, are more engaged with high-risk sexual behaviour, have higher HPV-16 serum antibody titer, use less tobacco and have better survival rates than in subjects with HPV-cytonegative oropharyngeal squamous cell carcinoma. In this subset of subjects the HPV-cytopositive carcinomatous cells have a distinct molecular profile. In contrast to HPV-cytopositive oropharyngeal squamous cell carcinoma, the causal association between HPV-16 and other high-risk HPV genotypes and squamous cell carcinoma of the oral mucosa is weak, and the nature of the association is unclear. It is likely that routine administration of HPV vaccination against high-risk HPV genotypes before the start of sexual activity will bring about a reduction in the incidence of HPV-mediated oral and oropharyngeal squamous cell carcinoma. This article focuses on aspects of HPV infection of the mouth and the oropharynx with emphasis on the link between HPV and squamous cell carcinoma, and on the limitations of the available diagnostic tests in identifying a cause-and-effect relationship of HPV with squamous cell carcinoma of the mouth and oropharynx. PMID:20633288

  13. Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas

    OpenAIRE

    Brown, J.W.; Fishman, L.M.

    2000-01-01

    Over a 15-year period, our university-based laboratory obtained 125 adrenal tumors, of which 15 (12%) were adrenal cortical carcinomas. Of these, 6 (40% of the carcinomas) occurred in patients with clear clinical manifestations of steroid hormone excess. Adrenal cortical carcinoma cells derived from the surgically resected tumors in 4 of these patients were isolated and established in primary culture. Radiotracer steroid interconversion studies were carried out with these cultures and also on...

  14. EXPRESSION AND SIGNIFICANCE OF ERK PROTEIN IN HUMAN BREAST CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    张秀梅; 李柏林; 宋敏; 宋继谒

    2004-01-01

    Objective: To investigate the expression of ERK and p-ERK protein in human breast cancer and their corresponding tissue, to assess the significance of ERK signal pathway in tumorigenesis and progression of breast carcinoma. Methods: 40 breast cancer cases were used in S-P immunohistochemistry technique and Western Blot study. Results: The expression of ERK1, ERK2, and p- ERK protein levels increased remarkably in breast cancer tissues in comparison to normal tissues (P<0.01). The expression was upregulated by 1.32-, 1.53-and 4.27-fold, respectively. The overexpressions of ERK1, ERK2, and p- ERK proteins were obviously correlated with clinical stage of breast cancer. Protein levels of ERK and p-ERK were higher in stage III patients than in stage I and stage II patients (P<0.05). These proteins were strongly related with axillary lymph node metastasis of breast cancer, but not correlated with histopathological type and status of ER and PR of breast cancer. Expression of ERK1, and ERK2, protein showed a positive linear correlation. Conclusion: ERK signal transduction pathway is a key factor during human breast tumorigenesis and breast cancer progression.

  15. 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.

  16. 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

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

    Directory of Open Access Journals (Sweden)

    Alyaa M Abdel-Haleem

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

  18. Association of human papilloma virus infection and oral squamous cell carcinoma in Bangladesh.

    Science.gov (United States)

    Akhter, Mahmuda; Ali, Liaquat; Hassan, Zahid; Khan, Imran

    2013-03-01

    Oral squamous cell carcinoma is the sixth most common malignancy worldwide. In Bangladesh, it comprises 20% of the whole body malignancies. Several studies found that 15% to 25% of oropharyngeal cancer cases are associated with human papilloma virus (HPV). This study is done to find the association of human papilloma virus subtypes, particularly HPV type 16 and HPV type 18, with the oral squamous cell carcinoma in Bangladeshi patients. In total, 34 diagnosed patients of oral squamous cell carcinoma were included in the study. Extracted DNA from the cancerous tissues was checked for PCR reaction to detect the subtypes of human papilloma virus. Data of the present study suggest that oral squamous cell carcinoma are almost absent in Bangladeshi patients with human papilloma virus, particularly HPV 16 and 18.

  19. Association of Human Papilloma Virus Infection and Oral Squamous Cell Carcinoma in Bangladesh

    Science.gov (United States)

    Ali, Liaquat; Hassan, Zahid; Khan, Imran

    2013-01-01

    Oral squamous cell carcinoma is the sixth most common malignancy worldwide. In Bangladesh, it comprises 20% of the whole body malignancies. Several studies found that 15% to 25% of oropharyngeal cancer cases are associated with human papilloma virus (HPV). This study is done to find the association of human papilloma virus subtypes, particularly HPV type 16 and HPV type 18, with the oral squamous cell carcinoma in Bangladeshi patients. In total, 34 diagnosed patients of oral squamous cell carcinoma were included in the study. Extracted DNA from the cancerous tissues was checked for PCR reaction to detect the subtypes of human papilloma virus. Data of the present study suggest that oral squamous cell carcinoma are almost absent in Bangladeshi patients with human papilloma virus, particularly HPV 16 and 18. PMID:23617206

  20. Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    Chen Chang-Jie

    2010-10-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC still is a big burden for China. In recent years, the third-generation platinum compounds have been proposed as potential active agents for HCC. However, more experimental and clinical data are warranted to support the proposal. In the present study, the effect of lobaplatin was assessed in five HCC cell lines and the underlying molecular mechanisms in terms of cell cycle kinetics were explored. Methods Cytotoxicity of lobaplatin to human HCC cell lines was examined using MTT cell proliferation assay. Cell cycle distribution was determined by flow cytometry. Expression of cell cycle-regulated genes was examined at both the mRNA (RT-PCR and protein (Western blot levels. The phosphorylation status of cyclin-dependent kinases (CDKs and retinoblastoma (Rb protein was also examined using Western blot analysis. Results Lobaplatin inhibited proliferation of human HCC cells in a dose-dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1, pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27. Conclusion Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC.

  1. Association of Human Papilloma Virus Infection and Oral Squamous Cell Carcinoma in Bangladesh

    OpenAIRE

    Akhter, Mahmuda; Ali, Liaquat; Hassan, Zahid; Khan, Imran

    2013-01-01

    Oral squamous cell carcinoma is the sixth most common malignancy worldwide. In Bangladesh, it comprises 20% of the whole body malignancies. Several studies found that 15% to 25% of oropharyngeal cancer cases are associated with human papilloma virus (HPV). This study is done to find the association of human papilloma virus subtypes, particularly HPV type 16 and HPV type 18, with the oral squamous cell carcinoma in Bangladeshi patients. In total, 34 diagnosed patients of oral squamous cell car...

  2. Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion

    International Nuclear Information System (INIS)

    Wu Xiaofeng; Fan Jia; Wang Xiaoying; Zhou Jian; Qiu Shuangjian; Yu Yao; Liu Yinkun; Tang Zhaoyou

    2007-01-01

    CC chemokine receptor 1 (CCR1) has an important role in the recruitment of leukocytes to the site of inflammation. The migration and metastasis of tumor cells shares many similarities with leukocyte trafficking, which is mainly regulated by chemokine receptor-ligand interactions. CCR1 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues with unknown functions. In this study, we silenced CCR1 expression in the human HCC cell line HCCLM3 using artificial microRNA (miRNA)-mediated RNA interference (RNAi) and examined the invasiveness and proliferation of CCR1-silenced HCCLM3 cells and the matrix metalloproteinase (MMP) activity. The miRNA-mediated knockdown expression of CCR1 significantly inhibited the invasive ability of HCCLM3 cells, but had only a minor effect on the cellular proliferation rate. Moreover, CCR1 knockdown significantly reduced the secretion of MMP-2. Together, these findings indicate that CCR1 has an important role in HCCLM3 invasion and that CCR1 might be a new target of HCC treatment

  3. The influence of human papillomavirus on nasopharyngeal carcinoma in Japan.

    Science.gov (United States)

    Kano, Makoto; Kondo, Satoru; Wakisaka, Naohiro; Moriyama-Kita, Makiko; Nakanishi, Yosuke; Endo, Kazuhira; Murono, Shigeyuki; Nakamura, Hiroyuki; Yoshizaki, Tomokazu

    2017-06-01

    Although Japan is a non-endemic area with nasopharyngeal carcinoma (NPC), the proportion of WHO type I NPC in Japan are different from that in non-endemic areas such as North America and Europe. Recently, it is said that not only Epstein-Barr virus (EBV) but also human papillomavirus (HPV) has an influence on NPC in non-endemic areas. The aim of this study is to clarify the influence of HPV on NPC in Japan. Paraffin-embedded tumor specimens were available for 59 patients with NPC diagnosed between 1996 and 2015. We detected the virus status by p16 immunohistochemistry, HPV PCR, and in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA. Kaplan-Meier curves were used to compare the overall survival by viral status. Among the 59 patients, 49 (83%) were EBV-positive/HPV-negative, 2 (3%) were EBV-positive/HPV-positive, and 8 (16%) were EBV-negative/HPV-negative. All HPV-positive NPCs were co-infected with EBV. There were no significant differences between the overall survival in the three groups (p=0.111). In Japan, HPV was detected in a few patients with NPC, and we suggest that HPV has no influence on NPC carcinogenesis in this population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  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. 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 ...

  6. 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. ...

  7. 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 ...

  8. 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

  9. 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.

  10. 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, ...

  11. 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.

  12. 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.

  13. Effects of cholera toxin on human colon carcinoma cell lines.

    Science.gov (United States)

    Barkla, D H; Whitehead, R H; Hayward, I P

    1992-10-01

    This study reports on changes in morphology and membrane transport in 5 human colon carcinoma cell lines treated with cholera toxin (CT). Three of the cell lines that grew as monolayers (LIM 1215, LIM 1899, LIM 2099) and 1 that grew as floating clumps (LIM 2408) did not show morphological changes after CT treatment. However, cell line LIM 1863 that grows as floating "crypt-like" organoids showed rapid and distinctive changes in morphology and membrane transport after CT treatment. At 1 and 6 hrs after CT treatment, light and transmission electron microscopy revealed rapid dilatation of the central lumen of organoids and the appearance of 2 populations of apical vesicular inclusions. The first population was unusual in being non-membrane bound and limited by fuzzy filamentous material. The second population was membrane bound. Scanning electron microscopy at 1-6 hr after CT treatment showed swelling and loss of surface microvilli on some, but not all, cells. At 24 hr after CT treatment the majority of organoids showed evidence of fluid accumulation and small apical vesicles coalesced to form large single vacuoles that obliterated normal cell morphology. By 48 hr, continued swelling produced extreme attenuation of the plasma membrane with cells taking on an "endothelial cell-like" appearance. The response to CT was dose-dependent. Uptake studies using 86Rubidium and blocking studies using ouabain and amiloride indicated that CT is acting on the Na+/K+ ATPase membrane pump to cause the increased fluid uptake by LIM 1863 cells. This study is the first to report specific morphological changes in intestine-derived cells in response to CT.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Automated quantification of aligned collagen for human breast carcinoma prognosis

    Directory of Open Access Journals (Sweden)

    Jeremy S Bredfeldt

    2014-01-01

    Full Text Available Background: Mortality in cancer patients is directly attributable to the ability of cancer cells to metastasize to distant sites from the primary tumor. This migration of tumor cells begins with a remodeling of the local tumor microenvironment, including changes to the extracellular matrix and the recruitment of stromal cells, both of which facilitate invasion of tumor cells into the bloodstream. In breast cancer, it has been proposed that the alignment of collagen fibers surrounding tumor epithelial cells can serve as a quantitative image-based biomarker for survival of invasive ductal carcinoma patients. Specific types of collagen alignment have been identified for their prognostic value and now these tumor associated collagen signatures (TACS are central to several clinical specimen imaging trials. Here, we implement the semi-automated acquisition and analysis of this TACS candidate biomarker and demonstrate a protocol that will allow consistent scoring to be performed throughout large patient cohorts. Methods: Using large field of view high resolution microscopy techniques, image processing and supervised learning methods, we are able to quantify and score features of collagen fiber alignment with respect to adjacent tumor-stromal boundaries. Results: Our semi-automated technique produced scores that have statistically significant correlation with scores generated by a panel of three human observers. In addition, our system generated classification scores that accurately predicted survival in a cohort of 196 breast cancer patients. Feature rank analysis reveals that TACS positive fibers are more well-aligned with each other, are of generally lower density, and terminate within or near groups of epithelial cells at larger angles of interaction. Conclusion: These results demonstrate the utility of a supervised learning protocol for streamlining the analysis of collagen alignment with respect to tumor stromal boundaries.

  15. Utility of early dynamic and delayed post-diuretic 18F-FDG PET/CT SUVmax in predicting tumour grade and T-stage of urinary bladder carcinoma: results from a prospective single centre study.

    Science.gov (United States)

    Sharma, Abhishek; Mete, Uttam K; Sood, Ashwani; Kakkar, Nandita; Gorla, Arun K R; Mittal, Bhagwant R

    2017-04-01

    Accurate pre-treatment grading and staging of bladder cancer are vital for better therapeutic decision and prognosis. The aim of the present study was to evaluate the correlation between maximum standardized uptake value (SUV max ) calculated during early dynamic and post-diuretic fluorine-18 fludeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/CT studies with grade and pT-stage of bladder cancer. 39 patients with suspected/proven bladder carcinoma underwent 10-min early dynamic pelvic imaging and delayed post-diuretic whole-body FDG PET/CT imaging. SUV max of the lesions derived from both studies was compared with grade and pT-stage. Relationship of SUV max with grade and pT-stage was analyzed using independent sample t-test and analysis of variance. SUV max of the early dynamic imaging showing tumour perfusion was independent from the SUV max of delayed imaging. High-grade tumours showed higher SUV max than low-grade tumours in the early dynamic imaging (5.4 ± 1.4 vs 4.7 ± 1.6; p-value 0.144) with statistically significant higher value in Stage pT1 tumours (6.8 ± 0.8 vs 5.5 ± 1.2; p-value 0.04). Non-invasive pTa tumours had significantly less SUV max than higher stage tumours during early dynamic imaging [F(4,29) = 6.860, p 0.001]. Early dynamic imaging may have a role in predicting the grade and aggressiveness of the bladder tumours and thus can help in treatment planning and prognostication. Advances in knowledge: Dynamic PET/CT is a limitedly explored imaging technique. This prospective pilot study demonstrates the utility of this modality as a potential adjunct to standard FDG PET/CT imaging in predicting the grade and aggressiveness of the bladder tumours and thus can impact the patient management.

  16. 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.

  17. 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...

  18. Endostar, a recombined humanized endostatin, enhances the radioresponse for human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts in mice

    International Nuclear Information System (INIS)

    Wen Qinglian; Meng Maobin; Tu Lingli; Jia Li; Zhou Lin; Xu Yong; Lu You; Yang Bo

    2009-01-01

    The purpose of this paper is to determine the efficacy of combining radiation therapy with endostar, a recombined humanized endostatin, in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts. Tumor xenografts were established in the hind limb of male athymic nude mice (BALB/c-nu) by subcutaneous transplantation. The tumor-bearing mice were assigned into four treatment groups: sham therapy (control), endostar (20 mg/kg, once daily for 10 days), radiation therapy (6 Gray per day to 30 Gray, once a day for 1 week), and endostar plus radiation therapy (combination). The experiment was repeated and mice were killed at days 3, 6, and 10 after initiation therapy, and the tumor tissues and blood samples were collected to analyze the kinetics of antitumor, antiangiogenesis, and antivascularization responses of different therapies. In human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts, endostar significantly enhanced the effects of tumor growth inhibition, endothelial cell and tumor cell apoptosis induction, and improved tumor cell hypoxia of radiation therapy. Histological analyses demonstrated that endostar plus radiation also induced a significant reduction in microvascular density, microvascular area, and vascular endothelial growth factor and matrix metalloproteinase-2 expression compared with radiation and endostar alone respectively. We concluded that endostar significantly sensitized the function of radiation in antitumor and antiangiogenesis in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts by increasing the apoptosis of the endothelial cell and tumor cell, improving the hypoxia of the tumor cell, and changing the proangiogenic factors. These data provided a rational basis for clinical practice of this multimodality therapy. (author)

  19. Human Papilloma Virus (HPV) Induced Head & Neck Squamous Cell Carcinoma: A Comprehensive Retrospect

    Science.gov (United States)

    Nishat, Roquaiya; Ramachandra, Sujatha; Kumar, Harish; Bandyopadhyay, Alokenath

    2015-01-01

    Head and Neck Squamous Cell Carcinoma accounts for the sixth most common malignancy occurring worldwide with tobacco and alcohol being the two well established risk factors. In the recent years, substantial evidence has been obtained that Human Papilloma Virus (HPV) associated head and neck cancers are on the rise. This article provides an insight into the structure of HPV genome, molecular pathogenesis, detection methods and clinical implications of HPV positive Head and Neck Squamous Cell Carcinoma. PMID:26266234

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Nine cases of bladder cancer occurring in occupational dye users

    OpenAIRE

    村瀬, 達良; 高士, 宗久; 青田, 泰博; 下地, 敏雄; 三宅, 弘治; 三矢, 英輔

    1985-01-01

    Workers in the dye manufacturing industry have a high risk of urinary bladder cancer. There may also be a high relative risk of bladder cancer in occupational dye users. Nine occupational dye users were found to have bladder cancer. The period of engaging with dye work ranged from 5 to 40 years. Seven patients had bladder cancer and the other 2 patients had lesions both in the bladder and in the renal pelvis. Histopathology of all cases was transitional cell carcinoma. Three cases were classi...

  2. Albumin Suppresses Human Hepatocellular Carcinoma Proliferation and the Cell Cycle

    Directory of Open Access Journals (Sweden)

    Shunsuke Nojiri

    2014-03-01

    Full Text Available Many investigations have revealed that a low recurrence rate of hepatocellular carcinoma (HCC is associated with high serum albumin levels in patients; therefore, high levels of serum albumin are a major indicator of a favorable prognosis. However, the mechanism inhibiting the proliferation of HCC has not yet been elucidated, so we investigated the effect of serum albumin on HCC cell proliferation. Hep3B was cultured in MEM with no serum or containing 5 g/dL human albumin. As control samples, Prionex was added to generate the same osmotic pressure as albumin. After 24-h incubation, the expressions of α-fetoprotein (AFP, p53, p21, and p57 were evaluated with real-time PCR using total RNA extracted from the liver. Protein expressions and the phosphorylation of Rb (retinoblastoma were determined by Western blot analysis using total protein extracted from the liver. For flow cytometric analysis of the cell cycle, FACS analysis was performed. The percentages of cell cycle distribution were evaluated by PI staining, and all samples were analyzed employing FACScalibur (BD with appropriate software (ModFit LT; BD. The cell proliferation assay was performed by counting cells with using a Scepter handy automated cell counter (Millipore. The mRNA levels of AFP relative to Alb(−: Alb(−, Alb(+, and Prionex, were 1, 0.7 ± 0.2 (p < 0.001 for Alb(−, and 1 ± 0.3, respectively. The mRNA levels of p21 were 1, 1.58 ± 0.4 (p = 0.007 for Alb(− and p = 0.004 for Prionex, and 0.8 ± 0.2, respectively. The mRNA levels of p57 were 1, 4.4 ± 1.4 (p = 0.002 for Alb(− and Prionex, and 1.0 ± 0.1, respectively. The protein expression levels of Rb were similar in all culture media. The phosphorylation of P807/811 and P780 of Rb protein was reduced in Alb(+. More cells in the G0/G1 phase and fewer cells in S and G2/M phases were obtained in Alb(+ than in Alb(− (G0/G1: 60.9%, 67.7%, 61.5%; G2/M: 16.5%, 13.1%, 15.6%; S: 22.6%, 19.2%, 23.0%, Alb(−, Alb

  3. Comprehensive profiling and localisation of the matrix metalloproteinases in urothelial carcinoma

    OpenAIRE

    Wallard, M J; Pennington, C J; Veerakumarasivam, A; Burtt, G; Mills, I G; Warren, A; Leung, H Y; Murphy, G; Edwards, D R; Neal, D E; Kelly, J D

    2006-01-01

    The matrix metalloproteinases (MMPs) are endopeptidases which break down the extracellular matrix and regulate cytokine and growth factor activity. Several MMPs have been implicated in the promotion of invasion and metastasis in a broad range of tumours including urothelial carcinoma. In this study, RNA from 132 normal bladder and urothelial carcinoma specimens was profiled for each of the 24 human MMPs, the four endogenous tissue inhibitors of MMPs (TIMPs) and several key growth factors and ...

  4. The management of invasive transitional cell carcinoma of the bladder. Results of definitive and preoperative radiation therapy in 390 patients treated at the Prince of Wales Hospital, Sydney, Australia.

    Science.gov (United States)

    Mameghan, H; Fisher, R J; Watt, W H; Meagher, M J; Rosen, I M; Mameghan, J; Brook, S; Tynan, A P; Korbel, E I; Millard, R J

    1992-06-01

    The treatment results for invasive transitional cell carcinoma (TCC) of the bladder were assessed in a series of 390 patients referred to the Department of Radiation Oncology at the Prince of Wales Hospital, Sydney, Australia, during the period 1977 to 1988. These patients were managed by one of two strategies: cystectomy (87 patients) and radiation therapy (303 patients). Actuarial survival rates (death from any cause) were determined and comparisons were made using log-rank tests and Cox regression analyses. The mean follow-up time was 7.6 years. Independent prognostic factors for shorter survival were: the presence of a ureteric obstruction (P less than 0.001), increasing clinical stage (P less than 0.001), increasing patient age (P = 0.003), and earlier year of presentation (P = 0.008). Comparison of the two strategies indicated no significant difference in overall survival after adjusting for imbalances in prognostic factors (P = 0.007 unadjusted; P = 0.29 adjusted). The slightly longer survival of 46 patients from 1983 onward who received primary systemic chemotherapy (compared with 149 patients not given chemotherapy) was not statistically significant (P = 0.12 unadjusted; P = 0.56 adjusted for prognostic factors). The 5-year actuarial rates of severe complications were 8.0% after cystectomy and 5.3% after radiation therapy. In 303 patients treated by definitive radiation therapy, the 5-year actuarial rate of freedom from bladder failure for all clinical tumor stages was 44% (Tx, 67%; T1, 45%; T2, 56%; T3, 39%; and T4, 39%). These results suggest that definitive radiation therapy is a viable alternative to radical cystectomy for patients with invasive TCC of the bladder.

  5. 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.

  6. Role of human papillomavirus in oropharyngeal squamous cell carcinoma: A review

    Science.gov (United States)

    Woods, Robbie SR; O’Regan, Esther M; Kennedy, Susan; Martin, Cara; O’Leary, John J; Timon, Conrad

    2014-01-01

    Human papillomavirus (HPV) has been implicated in the pathogenesis of a subset of oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in relation to the management of head and neck squamous cell carcinoma have been changing. Research into HPV-related oropharyngeal squamous cell carcinoma is rapidly expanding, however many molecular pathological and clinical aspects of the role of HPV remain uncertain and are the subject of ongoing investigation. A detailed search of the literature pertaining to HPV-related oropharyngeal squamous cell carcinoma was performed and information on the topic was gathered. In this article, we present an extensive review of the current literature on the role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to epidemiology, risk factors, carcinogenesis, biomarkers and clinical implications. HPV has been established as a causative agent in oropharyngeal squamous cell carcinoma and biologically active HPV can act as a prognosticator with better overall survival than HPV-negative tumours. A distinct group of younger patients with limited tobacco and alcohol exposure have emerged as characteristic of this HPV-related subset of squamous cell carcinoma of the head and neck. However, the exact molecular mechanisms of carcinogenesis are not completely understood and further studies are needed to assist development of optimal prevention and treatment modalities. PMID:24945004

  7. Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group: 2011 consensus guidelines for curative radiotherapy for urothelial carcinoma of the bladder

    International Nuclear Information System (INIS)

    Hindson, Benjamin R.; Turner, Sandra L.; Millar, Jeremy L.

    2012-01-01

    Curative radiotherapy, with or without concurrent chemotherapy, is recognized as a standard treatment option for muscle-invasive bladder cancer. It is commonly used for two distinct groups of patients: either for those medically unfit for surgery, or as part of a 'bladder preserving' management plan incorporating the possibility of salvage cystectomy. However, in both situations, the approach to radiotherapy varies widely around the world. The Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group recognised a need to develop consistent, evidence-based guidelines for patient selection and radiotherapy technique in the delivery of curative radiotherapy. Following a workshop convened in May 2009, a working party collated opinions and conducted a wide literature appraisal linking each recommendation with the best available evidence. This process was subject to ongoing re-presentation to the Faculty of Radiation Oncology Genito-Urinary Group members prior to final endorsement. These Guidelines include patient selection, radiation target delineation, dose and fractionation schedules, normal tissue constraints and investigational techniques. Particular emphasis is given to the rationale for the target volumes described. These Guidelines provide a consensus-based framework for the delivery of curative radiotherapy for muscle-invasive bladder cancer. Widespread input from radiation oncologists treating bladder cancer ensures that these techniques are feasible in practice. We recommend these Guidelines be adopted widely in order to encourage a uniformly high standard of radiotherapy in this setting, and to allow for better comparison of outcomes.

  8. Histological grading of papillary urothelial carcinoma of the bladder: prognostic value of the 1998 WHO/ISUP classification system and comparison with conventional grading systems

    NARCIS (Netherlands)

    Oosterhuis, J. W. A.; Schapers, R. F. M.; Janssen-Heijnen, M. L. G.; Pauwels, R. P. E.; Newling, D. W.; ten Kate, F.

    2002-01-01

    AIM: To test the prognostic value of the 1998 WHO/ISUP (World Health Organisation/International Society of Urologic Pathology) consensus classification system in Ta papillary urothelial neoplasms of the bladder. METHODS: The histological slides of 322 patients with a primary Ta tumour were

  9. Detection of the E7 transform gene of human papilloma virus type 16 in human oral squamous cell carcinoma.

    Science.gov (United States)

    Wang, J; Li, J; Huang, H; Fu, Y

    1998-12-01

    To determine, with the use of polymerase chain reaction, the prevalence of human papillomavirus (HPV) 16 in 30 patients with primary oral squamous cell carcinoma (OSCC) and 30 healthy control patients. DNA was extracted from freshly frozen tumor tissues of 30 patients with primary oral squamous cell carcinoma and from the oral mucosa of 30 controls. A pair of specific primers of the E7 early gene of HPV 16 were designed. PCR products were run by 1.5% agarose gel and the results of electrophoresis were photographed. HPV 16 was detected in 36.7% (11/30) of oral squamous cell carcinoma patients and 11.1% (4/30) of controls. HPV 16 has a significant association with oral squamous cell carcinoma. However, the role HPV 16 plays in the tumorigenesis of oral cancer and its clinical significance remain to be investigated.

  10. Expression of Anti-apoptotic Protein BAG3 in Human Sebaceous Gland Carcinoma of the Eyelid.

    Science.gov (United States)

    Yunoki, Tatsuya; Tabuchi, Yoshiaki; Hayashi, Atsushi

    2017-04-01

    Bcl-2-associated athanogene 3 (BAG3), a co-chaperone of heat shock protein 70 (HSP70), has been shown to play a role in anti-apoptosis of various malignant tumors. In this study, the expression of BAG3 was examined in human sebaceous gland carcinoma of the eyelid. The expression of BAG3 was evaluated by immunohistochemistry of surgical samples from 5 patients with sebaceous gland carcinoma in the eyelid. BAG3 was positive diffusely in the cytoplasm in all patients. The average positive rate of BAG3 was 73.0±26.0% in tumor cells of all patients. BAG3 was highly expressed in sebaceous gland carcinoma of the eyelid. BAG3 may play an important role in the pathogenesis and progression of sebaceous gland carcinoma of the eyelid. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. 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...

  12. 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.

  13. 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

  14. 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.

  15. 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)

  16. 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

  17. Alterations of the Human Skin N- and O-Glycome in Basal Cell Carcinoma and Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Uwe Möginger

    2018-03-01

    Full Text Available The glycome of one of the largest and most exposed human organs, the skin, as well as glycan changes associated with non-melanoma skin cancers have not been studied in detail to date. Skin cancers such as basal cell carcinoma (BCC and squamous cell carcinoma (SCC are among the most frequent types of cancers with rising incidence rates in the aging population. We investigated the healthy human skin N- and O-glycome and its changes associated with BCC and SCC. Matched patient samples were obtained from frozen biopsy and formalin-fixed paraffin-embedded tissue samples for glycomics analyses using two complementary glycomics approaches: porous graphitized carbon nano-liquid chromatography electro spray ionization tandem mass spectrometry and capillary gel electrophoresis with laser induced fluorescence detection. The human skin N-glycome is dominated by complex type N-glycans that exhibit almost similar levels of α2-3 and α2-6 sialylation. Fucose is attached exclusively to the N-glycan core. Core 1 and core 2 type O-glycans carried up to three sialic acid residues. An increase of oligomannose type N-glycans and core 2 type O-glycans was observed in BCC and SCC, while α2-3 sialylation levels were decreased in SCC but not in BCC. Furthermore, glycopeptide analyses provided insights into the glycoprotein candidates possibly associated with the observed N-glycan changes, with glycoproteins associated with binding events being the most frequently identified class.

  18. 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.

  19. High-risk human papillomavirus (HPV) DNA sequences in metaplastic breast carcinomas of Mexican women

    International Nuclear Information System (INIS)

    Herrera-Goepfert, Roberto; Vela-Chávez, Teresa; Carrillo-García, Adela; Lizano-Soberón, Marcela; Amador-Molina, Alfredo; Oñate-Ocaña, Luis F; Hallmann, Rita Sotelo-Regil

    2013-01-01

    Metaplastic carcinoma, an uncommon subtype of breast cancer, is part of the spectrum of basal-like, triple receptor-negative breast carcinomas. The present study examined 20 surgical specimens of metaplastic breast carcinomas, for the presence of high-risk Human papillomavirus (HPV), which is suspected to be a potential carcinogenic agent for breast carcinoma. Mastectomy specimens from patients harboring metaplastic breast carcinoma, as defined by the World Health Organization (WHO), and who attended the Instituto Nacional de Cancerologia in Mexico City, were retrieved from the files of the Department of Pathology accumulated during a 16-year period (1995–2008). Demographic and clinical information was obtained from patients’ medical records. DNA was extracted from formalin-fixed, paraffin-embedded tumors and HPV type-specific amplification was performed by means of Polymerase chain reaction (PCR). Quantitative Real-time (RT) PCR was conducted in HPV positive cases. Statistically, the association of continuous or categorical variables with HPV status was tested by the Student t, the Chi square, or Fisher’s exact tests, as appropriate. High-risk HPV DNA was detected in eight (40%) of 20 metaplastic breast carcinomas: seven (87.5%) HPV-16 and one (12.5%) HPV-18. Mean age of patients with HPV-positive cases was 49 years (range 24–72 years), the same as for HPV-negative cases (range, 30–73 years). There were not striking differences between HPV + and HPV– metaplastic carcinomas regarding clinical findings. Nearly all cases were negative for estrogen, progesterone and Human epidermal growth factor receptor 2 (HER2), but positive for Epidermal growth factor receptor (EGFR). High-risk HPV has been strongly associated with conventional breast carcinomas, although the subtle mechanism of neoplastic transformation is poorly understood. In Mexican patients, the prevalence of HPV infection among metaplastic breast carcinomas is higher than in non-metaplastic ones

  20. [Primary study on fluro [ 19F] berberine derivative for human hepatocellular carcinoma targetting in vitro].

    Science.gov (United States)

    Zhang, Tong; Wu, Xiaoai; Cai, Huawei; Liang, Meng; Fan, Chengzhong

    2017-04-01

    [ 18 F]HX-01, a Fluorine-18 labeled berberine derivative, is a potential positron emission tomography (PET) tumor imaging agent, while [ 19 F]HX-01 is a nonradioactive reference substance with different energy state and has the same physical and chemical properties. In order to collect data for further study of [ 18 F]HX-01 PET imaging of hepatocellular carcinoma in vivo , this study compared the uptake of [ 19 F]HX-01 by human hepatocellular carcinoma and normal hepatocytes in vitro . The target compound, [ 19 F]HX-01, was synthesized in one step using berberrubine and 3-fluoropropyl 4-methylbenzenesulfonate. Cellular uptake and localization of [ 19 F]HX-01 were performed by a fluorescence microscope in human hepatocellular carcinoma HepG2, SMMC-7721 and human normal hepatocyte HL-7702. Cellular proliferation inhibition and cell cytotoxicity assay of the [ 19 F]HX-01 were conducted using cell counting kit-8 (CCK-8) on HepG2, SMMC-7721 and HL-7702 cells. Fluorescent microscopy showed that the combining ability of [ 19 F]HX-01 to the carcinoma SMMC-7721 and HepG2 was higher than that to the normal HL-7702. Cellular proliferation inhibition assay demonstrated that [ 19 F]HX-01 leaded to a dose-dependent inhibition on SMMC-7721, HepG2, and HL-7702 proliferation. Cell cytotoxicity assay presented that the cytotoxicity of [ 19 F]HX-01 to SMMC-7721 and HepG2 was obviously higher than that to HL-7702. This in vitro study showed that [ 19 F]HX-01 had a higher selectivity on human hepatocellular carcinoma cells (SMMC-7721, HepG2) but has less toxicity to normal hepatocytes (HL-7702). This could set up the idea that the radioactive reference substance [ 18 F]HX-01 may be worthy of further development as a potential molecular probe targeting human hepatocellular carcinoma using PET.

  1. Urokinase-type plasminogen activator receptor (uPAR) expression is associated with T-stage and survival in urothelial carcinoma of the bladder

    DEFF Research Database (Denmark)

    Dohn, Line Hammer; Illemann, Martin; Høyer-Hansen, Gunilla

    2015-01-01

    OBJECTIVES: To evaluate the expression-and localization pattern of the urokinase-type plasminogen activator receptor (uPAR), focusing on its clinical implications in patients with urothelial neoplasia of the bladder treated with radical cystectomy. uPAR is a central molecule in tissue remodeling...... during cancer invasion and metastasis and is an established prognostic marker in cancer. The expression and localization of uPAR and its prognostic significance is only limitedly investigated in urothelial bladder neoplasia. MATERIALS AND METHODS: The expression-and localization pattern of u......PAR was investigated in formalin-fixed paraffin-embedded tumor tissue from 149 patients treated with radical cystectomy between 1988 and 2005. uPAR expression was determined by immunohistochemistry and scored as either negative or positive. Separate values were obtained for cancer cells, macrophages...

  2. Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas

    Directory of Open Access Journals (Sweden)

    Brown J.W.

    2000-01-01

    Full Text Available Over a 15-year period, our university-based laboratory obtained 125 adrenal tumors, of which 15 (12% were adrenal cortical carcinomas. Of these, 6 (40% of the carcinomas occurred in patients with clear clinical manifestations of steroid hormone excess. Adrenal cortical carcinoma cells derived from the surgically resected tumors in 4 of these patients were isolated and established in primary culture. Radiotracer steroid interconversion studies were carried out with these cultures and also on mitochondria isolated from homogenized tissues. Large tumors had the lowest steroidogenic activities per weight, whereas small tumors had more moderately depressed enzyme activities relative to cells from normal glands. In incubations with pregnenolone as substrate, 1 mM metyrapone blocked the synthesis of corticosterone and cortisol and also the formation of aldosterone. Metyrapone inhibition was associated with a concomitant increase in the formation of androgens (androstenedione and testosterone from pregnenolone. Administration of metyrapone in vivo before surgery in one patient resulted in a similar increase in plasma androstenedione, though plasma testosterone levels were not significantly affected. In cultures of two of four tumors examined, dibutyryl cAMP stimulated 11ß-hydroxylase activity modestly; ACTH also had a significant stimulatory effect in one of these tumors. Unlike results obtained with normal or adenomatous adrenal cortical tissues, mitochondria from carcinomatous cells showed a lack of support of either cholesterol side-chain cleavage enzyme complex or steroid 11ß-hydroxylase activity by Krebs cycle intermediates (10 mM isocitrate, succinate or malate. This finding is consistent with the concept that these carcinomas may tend to function predominantly in an anaerobic manner, rather than through the oxidation of Krebs cycle intermediates.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Clinical Implication of Elevated Human Cervical Cancer Oncogene-1 Expression in Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Liu, Ying; Li, Ke; Ren, Zhonghai; Li, Shenglei; Zhang, Hongyan; Fan, Qingxia

    2012-01-01

    The human cervical cancer oncogene 1 (HCCR-1), a novel human oncoprotein, has been shown to be upregulated in various human tumors and plays a critical role in tumorigenesis and tumor progression. Here, the authors investigated HCCR-1 level in esophageal squamous cell carcinoma (ESCC) tissues and assessed the correlation between HCCR-1 level and prognosis of the patients with ESCC. HCCR-1 levels were investigated by immunohistochemistry, in situ hybridization, real-time quantit...

  5. Development and evaluation of a training program for therapeutic radiographers as a basis for online adaptive radiation therapy for bladder carcinoma

    International Nuclear Information System (INIS)

    Foroudi, Farshad; Wong, Jacky; Kron, Tomas; Roxby, Paul; Haworth, Annette; Bailey, Alistair; Rolfo, Aldo; Paneghel, Andrea; Styles, Colin; Laferlita, Marcus; Tai, Keen Hun; Williams, Scott; Duchesne, Gillian

    2010-01-01

    Aims: Online adaptive radiotherapy requires a new level of soft tissue anatomy recognition and decision making by therapeutic radiographers at the linear accelerator. We have developed a therapeutic radiographer training workshop encompassing soft tissue matching for an online adaptive protocol for muscle invasive bladder cancer. Our aim is to present the training program, and its evaluation which compares pre and post training staff soft tissue matching and bladder contouring using Cone Beam Computer Tomography (CBCT). Materials and Methods: Prior to commencement of an online adaptive bladder protocol, a staff training program for 33 therapeutic radiographers, with a separate ethics approved evaluation component was developed. A multidisciplinary training program over two days was carried out with a total of 11 h of training, covering imaging technology, pelvic anatomy and protocol specific decision making in both practical and theoretical sessions. The evaluation included both pre training and post training testing of staff. Results: Pre training and post training, the standard deviations in the contoured bladder between participants in left-right direction were 0.64 vs 0.59 cm, superior-inferior 0.89 vs 0.77 cm and anterior-posterior direction was 0.88 vs 0.52 cm respectively. Similarly the standard deviation in the volume contoured decreased from 40.7 cc pre training to 24.5 cc post training. Time taken in contouring was reduced by the training program (19.8 vs 17.2 min) as was the discrepancy in choice of adaptive radiotherapy plans. The greatest reduction in variations in contouring was seen in staff whose pre training had the largest deviations from the reference radiation oncologist contours. Conclusion: A formalized staff training program is feasible, well received by staff and reduces variation in organ matching and contouring. The improvement was particularly noticed in staff who pre training had larger deviations from the reference standard.

  6. Influence of human papillomavirus on the clinical presentation of oropharyngeal carcinoma in the United States.

    Science.gov (United States)

    Stenmark, Matthew H; Shumway, Dean; Guo, Cui; Vainshtein, Jeffrey; Mierzwa, Michelle; Jagsi, Reshma; Griggs, Jennifer J; Banerjee, Mousumi

    2017-10-01

    Much of what is known about the significance of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma is derived from single-institution retrospective studies, post hoc analyses of tissue specimens from clinical trials, and tissue bank studies with a small sample size. The objective of this study is to investigate the impact of HPV on the frequency and clinical presentation of oropharyngeal carcinoma in a large, national sample with information from patients who underwent HPV testing. Retrospective, cross-sectional study. We identified a comprehensive national sample of 8,359 patients with oropharyngeal carcinoma and known HPV status diagnosed between 2010 and 2011 within the National Cancer Database. Multivariable logistic regression was used to assess correlates of patient and tumor characteristics on HPV status. Among patients with oropharyngeal carcinoma, the frequency of HPV-related