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Sample records for grade bladder cancer

  1. Proliposomal Intravesical Paclitaxel for Treatment of Low-Grade, Stage Ta, Non Muscle Invasive Bladder Cancer

    ClinicalTrials.gov

    2017-03-16

    Bladder Cancer Cell Transitional; Non-Muscle Invasive Bladder Cancer; Bladder Cancer; Urinary Bladder; Transitional Cell Carcinoma of the Bladder; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Urinary Bladder Diseases; Urologic Diseases

  2. Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology.

    PubMed

    Damrauer, Jeffrey S; Hoadley, Katherine A; Chism, David D; Fan, Cheng; Tiganelli, Christopher J; Wobker, Sara E; Yeh, Jen Jen; Milowsky, Matthew I; Iyer, Gopa; Parker, Joel S; Kim, William Y

    2014-02-25

    We sought to define whether there are intrinsic molecular subtypes of high-grade bladder cancer. Consensus clustering performed on gene expression data from a meta-dataset of high-grade, muscle-invasive bladder tumors identified two intrinsic, molecular subsets of high-grade bladder cancer, termed "luminal" and "basal-like," which have characteristics of different stages of urothelial differentiation, reflect the luminal and basal-like molecular subtypes of breast cancer, and have clinically meaningful differences in outcome. A gene set predictor, bladder cancer analysis of subtypes by gene expression (BASE47) was defined by prediction analysis of microarrays (PAM) and accurately classifies the subtypes. Our data demonstrate that there are at least two molecularly and clinically distinct subtypes of high-grade bladder cancer and validate the BASE47 as a subtype predictor. Future studies exploring the predictive value of the BASE47 subtypes for standard of care bladder cancer therapies, as well as novel subtype-specific therapies, will be of interest.

  3. Vesigenurtacel-L (HS-410) in the management of high-grade nonmuscle invasive bladder cancer.

    PubMed

    Keehn, Aryeh; Gartrell, Benjamin; Schoenberg, Mark P

    2016-12-01

    Unlike other malignancies, the death rate of bladder cancer has not declined in several decades, highlighting the need for new treatment options. In the emerging era of immunotherapy, therapeutic cancer vaccines are an attractive option to cure, control and prevent cancer. Despite this, finding a feasible and efficacious vaccine platform has proven elusive across all malignancies. Vesigenurtacel-L is the first whole cell, allogeneic vaccine intended to treat high-grade, nonmuscle invasive bladder cancer. This type of vaccine technology for bladder cancer is novel, and has the potential to be both economically and logistically feasible.

  4. Bladder cancer.

    PubMed Central

    Leung, H. Y.; Griffiths, T. R.; Neal, D. E.

    1996-01-01

    Bladder cancer is the fourth most common cancer in England and Wales. The most common presenting symptom is macroscopic haematuria. The management options for superficial and invasive bladder cancer depend on the stage at presentation. Most superficial bladder cancers are managed by transurethral resection and cytoscopic follow-up. The prognosis for patients with invasive bladder cancer is less good. The role of chemical, radiotherapeutic and surgical intervention are discussed. PMID:9015464

  5. Bladder cancer

    MedlinePlus

    ... workers, aluminum workers, leather workers, truck drivers, and pesticide applicators are at the highest risk. Chemotherapy: The ... Avoid exposure to chemicals linked to bladder cancer. Alternative Names Transitional cell carcinoma of the bladder; Urothelial ...

  6. Three serum metabolite signatures for diagnosing low-grade and high-grade bladder cancer

    PubMed Central

    Tan, Guangguo; Wang, Haibo; Yuan, Jianlin; Qin, Weijun; Dong, Xin; Wu, Hong; Meng, Ping

    2017-01-01

    To address the shortcomings of cystoscopy and urine cytology for detecting and grading bladder cancer (BC), ultrahigh performance liquid chromatography (UHPLC) coupled with Q-TOF mass spectrometry in conjunction with univariate and multivariate statistical analyses was employed as an alternative method for the diagnosis of BC. A series of differential serum metabolites were further identified for low-grade(LG) and high-grade(HG) BC patients, suggesting metabolic dysfunction in malignant proliferation, immune escape, differentiation, apoptosis and invasion of cancer cells in BC patients. In total, three serum metabolites including inosine, acetyl-N-formyl-5-methoxykynurenamine and PS(O-18:0/0:0) were selected by binary logistic regression analysis, and receiver operating characteristic (ROC) test based on their combined use for HG BC showed that the area under the curve (AUC) was 0.961 in the discovery set and 0.950 in the validation set when compared to LG BC. Likewise, this composite biomarker panel can also differentiate LG BC from healthy controls with the AUC of 0.993 and 0.991 in the discovery and validation set, respectively. This finding suggested that this composite serum metabolite signature was a promising and less invasive classifier for probing and grading BC, which deserved to be further investigated in larger samples. PMID:28382976

  7. Low-grade toxicity after conformal radiation therapy for prostate cancer-impact of bladder volume

    SciTech Connect

    Pinkawa, Michael . E-mail: mpinkawa@ukaachen.de; Fischedick, Karin; Asadpour, Branka; Gagel, Bernd; Piroth, Marc D.; Eble, Michael J.

    2006-03-01

    Purpose: To assess the impact of dose-volume histogram parameters on low-grade toxicity after radiotherapy for prostate cancer. Methods and Materials: Eighty patients have been surveyed prospectively before (time A), at the last day (B), 2 months after (C), and 16 months (median) after (D) radiotherapy (70.2 Gy) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Dose-volume histograms were correlated with urinary and bowel function/bother scores. Results: The initial bladder volume and the percentage of the bladder volume receiving 10%-90% of the prescription dose significantly correlated with urinary function/bother scores (significant cutoff levels found for all dose levels). Pain with urination proved to be mainly an acute problem, subsiding faster for patients with larger bladder volumes and smaller volumes inside particular isodose lines. At time D, persisting problems with smaller initial bladder volumes were a weak stream and an increased frequency of urination. Though bladder volume and planning target volume both independently have an influence on dose-volume histogram parameters for the bladder, bladder volume plays the decisive role for urinary toxicity. Conclusions: The patient's ability to fill the bladder has a major impact on the dose-volume histogram and both acute and late urinary toxicity.

  8. ADVANCES IN IMAGING TECHNOLOGIES IN THE EVALUATION OF HIGH-GRADE BLADDER CANCER

    PubMed Central

    Zlatev, Dimitar V.; Altobelli, Emanuela; Liao, Joseph C.

    2015-01-01

    Bladder cancer is a heterogeneous disease that ranges from low-grade variant with an indolent course, to high-grade subtype with a recurrent, progressive, and potentially lethal outcome. Accurate assessment for individualized treatment depends critically on the diagnostic accuracy of white light cystoscopy. Despite its central role, white light cystoscopy has several well-documented shortcomings including difficult flat lesion detection, imprecise tumor delineation that limits complete resection, differentiation between inflammation and malignancy, and grade and stage determination. As the limitations of white light cystoscopy contribute to the risk of cancer persistence, recurrence, and progression, there is a need for improved visualization of flat, multifocal, high-grade, and muscle-invasive lesions. Optical imaging technologies have emerged as an adjunct to white light cystoscopy with the goal to guide more effective treatment by improving cancer detection and patient stratification on the basis of grade and stage. Photodynamic diagnosis and narrow band imaging are macroscopic imaging modalities similar to white light cystoscopy, but provide additional contrast enhancement of bladder tumors and have been shown to improve detection rates. Confocal laser endomicroscopy and optical coherence tomography are microscopic imaging technologies that enable real-time high resolution, subsurface tissue characterization with spatial resolutions similar to histology. Molecular imaging offers the potential for the combination of optical imaging technologies with cancer-specific molecular agents to improve the specificity of disease detection. PMID:25882557

  9. Bladder Cancer Advocacy Network

    MedlinePlus

    ... Sexuality Life after Radical Cystectomy Women and Bladder Cancer Immunotherapy To watch the recordings and download the transcripts, click here! Look for more topics coming this spring! Bladder cancer is the fifth most commonly diagnosed cancer in ...

  10. Genetic and Epigenetic Alterations in Bladder Cancer

    PubMed Central

    2016-01-01

    Bladder cancer is one of the most common cancers worldwide, with a high rate of recurrence and poor outcomes as a result of relapse. Bladder cancer patients require lifelong invasive monitoring and treatment, making bladder cancer one of the most expensive malignancies. Lines of evidence increasingly point to distinct genetic and epigenetic alteration patterns in bladder cancer, even between the different stages and grades of disease. In addition, genetic and epigenetic alterations have been demonstrated to play important roles during bladder tumorigenesis. This review will focus on bladder cancer-associated genomic and epigenomic alterations, which are common in bladder cancer and provide potential diagnostic markers and therapeutic targets for bladder cancer treatment. PMID:27915480

  11. Tumor regression grade of urothelial bladder cancer after neoadjuvant chemotherapy: a novel and successful strategy to predict survival.

    PubMed

    Fleischmann, Achim; Thalmann, George N; Perren, Aurel; Seiler, Roland

    2014-03-01

    Histopathologic tumor regression grades (TRGs) after neoadjuvant chemotherapy predict survival in different cancers. In bladder cancer, corresponding studies have not been conducted. Fifty-six patients with advanced invasive urothelial bladder cancer received neoadjuvant chemotherapy before cystectomy and lymphadenectomy. TRGs were defined as follows: TRG1: complete tumor regression; TRG2: >50% tumor regression; TRG3: 50% or less tumor regression. Separate TRGs were assigned for primary tumors and corresponding lymph nodes. The prognostic impact of these 2 TRGs, the highest (dominant) TRG per patient, and competing tumor features reflecting tumor regression (ypT/ypN stage, maximum diameter of the residual tumor) were determined. Tumor characteristics in initial transurethral resection of the bladder specimens were tested for response prediction. The frequency of TRGs 1, 2, and 3 in the primary tumors were n=16, n=19, and n=21; corresponding data from the lymph nodes were n=31, n=9, and n=16. Interobserver agreement in determination of the TRG was strong (κ=0.8). Univariately, all evaluated parameters were significantly (P ≤ 0.001) related to overall survival; however, the segregation of the Kaplan-Meier curves was best for the dominant TRG. In multivariate analysis, only dominant TRG predicted overall survival independently (P=0.035). In transurethral resection specimens of the chemotherapy-naive bladder cancer, the only tumor feature with significant (P<0.03) predictive value for therapy response was a high proliferation rate. In conclusion, among all parameters reflecting tumor regression, the dominant TRG was the only independent risk factor. A favorable chemotherapy response is associated with a high proliferation rate in the initial chemotherapy-naive bladder cancer. This feature might help personalize neoadjuvant chemotherapy.

  12. AB266. Expression of long noncoding RNA lncRNA-n336928 is correlated with tumor stage and grade and overall survival in bladder cancer

    PubMed Central

    Chen, Tao; Wu, Changli; Hu, Hailong

    2016-01-01

    Background Long noncoding RNAs (lncRNAs) have been implicated playing important roles in human urologic cancers. Up to date, quite a few lncRNAs have been implicated as promising biomarkers for tumor early detection and prognosis monitoring. Methods In the present study, microarray analysis was initially performed to screen the differentially expressed lncRNAs between bladder cancer tissues and paired adjacent non-cancerous tissues (n=3).Subsequent qRT-PCR validation was conducted using tissue samples from 95 patients with bladder cancer. Results Results showed that the expression level of lncRNA-n336928 (noncode database ID: n336928) was significantly higher in bladder cancer tissues compared to that in adjacent noncancerous tissues (P<0.001). Chi-square test showed that expression of lncRNA-n336928 was positively correlated with bladder tumor stage and histological grade (P<0.001). Kaplan-Meier survival analysis revealed that patients with bladder cancer with high expression of lncRNA-n336928 had shorter overall survival time compared to patients with low expression of lncRNA-n336928. Multivariate analysis indicated that lncRNA-n336928 was an independent prognostic factor for overall survival for bladder cancer patients. Conclusions our study shows that high expression of lncRNA-n336928 is associated with the progression of bladder cancer, and that lncRNA-n336928 might serve as a biomarker for prognosis of bladder cancer

  13. Computer-assisted bladder cancer grading: α-shapes for color space decomposition

    NASA Astrophysics Data System (ADS)

    Niazi, M. K. K.; Parwani, Anil V.; Gurcan, Metin N.

    2016-03-01

    According to American Cancer Society, around 74,000 new cases of bladder cancer are expected during 2015 in the US. To facilitate the bladder cancer diagnosis, we present an automatic method to differentiate carcinoma in situ (CIS) from normal/reactive cases that will work on hematoxylin and eosin (H and E) stained images of bladder. The method automatically determines the color deconvolution matrix by utilizing the α-shapes of the color distribution in the RGB color space. Then, variations in the boundary of transitional epithelium are quantified, and sizes of nuclei in the transitional epithelium are measured. We also approximate the "nuclear to cytoplasmic ratio" by computing the ratio of the average shortest distance between transitional epithelium and nuclei to average nuclei size. Nuclei homogeneity is measured by computing the kurtosis of the nuclei size histogram. The results show that 30 out of 34 (88.2%) images were correctly classified by the proposed method, indicating that these novel features are viable markers to differentiate CIS from normal/reactive bladder.

  14. [Radiotherapy of bladder cancer].

    PubMed

    Riou, O; Chauvet, B; Lagrange, J-L; Martin, P; Llacer Moscardo, C; Charissoux, M; Lauche, O; Aillères, N; Fenoglietto, P; Azria, D

    2016-09-01

    Surgery (radical cystectomy) is the standard treatment of muscle-invasive bladder cancer. Radiochemotherapy has risen as an alternative treatment option to surgery as part as organ-sparing combined modality treatment or for patients unfit for surgery. Radiochemotherapy achieves 5-year bladder intact survival of 40 to 65% and 5-year overall survival of 40 to 50% with excellent quality of life. This article introduces the French recommendations for radiotherapy of bladder cancer: indications, exams, technique, dosimetry, delivery and image guidance.

  15. Elevated connexin 43 expression in arsenite-and cadmium-transformed human bladder cancer cells, tumor transplants and selected high grade human bladder cancers.

    PubMed

    Zhang, Ruowen; Wang, Liping; Garrett, Scott H; Sens, Donald A; Dunlevy, Jane R; Zhou, Xu Dong; Somji, Seema

    2016-10-01

    Connexin 43 has been shown to play a role in cell migration and invasion; however, its role in bladder cancer is not well defined. Previous studies from our laboratory have shown that the environmental pollutants arsenite and cadmium can cause malignant transformation of the immortalized urothelial cell line UROtsa. These transformed cells can form tumors in immune-compromised mice. The goal of the present study was to determine if connexin 43 is expressed in the normal human bladder, the arsenite and cadmiun-transformed UROtsa cells as well as human urothelial cancer. The results obtained showed that connexin 43 is not expressed in the epithelial cells of the human bladder but is expressed in immortalized cultures of human urothelial cells and the expression is variable in the arsenite and cadmium- transformed urothelial cell lines derived from these immortalized cells. Tumor heterotransplants generated from the transformed cells expressed connexin 43 and the expression was localized to areas of squamous differentiation. Immuno-histochemical analysis of human bladder cancers also showed that the expression of connexin 43 was localized to areas of the tumor that showed early features of squamous differentiation. Treatment of UROtsa cells with various concentrations of arsenite or cadmium did not significantly alter the expression level of connexin 43. In conclusion, our results show that the expression of connexin 43 is localized to the areas of the tumor that show squamous differentiation, which may be an indicator of poor prognosis. This suggests that connexin 43 has the potential to be developed as a biomarker for bladder cancer that may have the ability to invade and metastasize.

  16. Origins of Bladder Cancer.

    PubMed

    Czerniak, Bogdan; Dinney, Colin; McConkey, David

    2016-05-23

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

  17. What Is Bladder Cancer?

    MedlinePlus

    ... bladder, which is called the urothelium or transitional epithelium . As the cancer grows into or through the ... in the inner layer of cells (the transitional epithelium) but have not grown into the deeper layers. ...

  18. Low molecular weight cyclin E is associated with p27-resistant, high-grade, high-stage and invasive bladder cancer

    PubMed Central

    Zhang, Xin-Qiao; Bondaruk, Jolanta; Tucker, Susan L; Czerniak, P. Bogdan; Benedict, William F; Keyomarsi, Khandan

    2012-01-01

    Expression of low molecular weight (LMW) isoforms of cyclin E is a strong predictor of poor outcome in patients with breast cancer. The purpose of this study was to examine the expression of full-length and LMW cyclin E in bladder cancer cell lines and patient tumors. We used western blotting, immunoprecipitation and kinase assays to examine the expression and activity of key cell cycle-regulatory proteins in various human bladder cell lines, both tumorigenic and non-tumorigenic. We also analyzed cyclin E expression, kinase activity and immune complex binding partners in 43 tissue samples from grade 2 and 3 transitional cell carcinomas. Cyclin E was overexpressed and LMW isoforms were present only in bladder cancer cells. Overexpression of LMW isoforms of cyclin E and increased cyclin E kinase activity were both significantly associated with tumorigenicity of the bladder cell lines (p = 0.005 and 0.022, respectively). Binding of the cyclin-dependent kinase inhibitors p21 and p27 to LMW cyclin E did not inhibit the kinase activity of cyclin E and cyclin-dependent kinase 2 in primary tumor samples overexpressing LMW cyclin E. Full-length and LMW cyclin E were significantly overexpressed in grade 3 tumors compared with grade 2 tumors (p = 0.004). Finally, LMW cyclin E levels were significantly associated with a non-papillary growth pattern (p = 0.031) and invasiveness (p = 0.021) of the bladder tumors and poor overall survival (p = 0.06). These results suggest that LMW cyclin E can be used as a new prognostic marker for bladder cancer. PMID:22441703

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

    Cancer.gov

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

  20. Innovation in Bladder Cancer Immunotherapy.

    PubMed

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

    2016-10-01

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

  1. p53 nuclear protein accumulation correlates with mutations in the p53 gene, tumor grade, and stage in bladder cancer.

    PubMed

    Esrig, D; Spruck, C H; Nichols, P W; Chaiwun, B; Steven, K; Groshen, S; Chen, S C; Skinner, D G; Jones, P A; Cote, R J

    1993-11-01

    .01). We conclude that the immunohistochemical detection of p53 nuclear accumulation in formalin-fixed, paraffin-embedded tissue is highly associated with mutations in the p53 gene; this association has now been demonstrated in a large number of tumors. The heterogeneity of p53 nuclear reactivity seems to be related to the site of mutation in the p53 gene. A small proportion of tumors with a p53 gene mutation do not demonstrate immunohistochemically detectable p53 nuclear accumulation. Furthermore, a small but substantial proportion of tumors demonstrate p53 nuclear reactivity but do not show detectable mutations in the p53 gene by SSCP. Finally, both grade and stage of bladder cancer are related to p53 alterations, detected by immunohistochemistry or molecular methods.(ABSTRACT TRUNCATED AT 400 WORDS)

  2. [Diet in bladder cancer ethiopathogenesis].

    PubMed

    Radosavljević, V; Ilić, M; Janković, S; Djokić, M

    2005-01-01

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

  3. Chemoprevention of bladder cancer.

    PubMed

    Kamat, Ashish M; Lamm, Donald L

    2002-02-01

    The data presented herein, although highly supportive for a protective role of various nutrients against bladder cancer, are far from definitive. Many authorities question the validity of current recommendations for nutritional chemoprevention against bladder cancer. The reason for the wide variations reported in epidemiologic studies lies in the nature of observational studies. Dietary studies are limited in their conclusions because the protection afforded by the consumption of a particular nutrient may be multifactorial, with different components of the food exerting potential chemopreventive effects. Furthermore, measuring levels of nutrients in the food intake of populations is confounded by factors that might affect these levels and also the incidence of cancer. For example, vitamin A can come from animal or vegetarian sources. Because animal fat has been identified as a potential carcinogen in man, depending on the source of the vitamin, varying levels of protection might be deduced. In addition, chemoprevention studies using dietary supplements are expected to have mild effects, and large studies would be required to confirm statistical significance. Even with agents such as intravesical chemotherapy, only half the studies achieve statistical significance [29]. Prospective randomized trials with a large sample size, longer follow-up, and an extended duration of treatment are needed to clarify the association between micronutrients and cancer protection. With these caveats in mind, several recommendations can be made. Simple measures, such as drinking more fluids (especially water), can have a profound impact on the incidence of bladder cancer. Vitamins are being extensively studied in chemopreventive trials for different cancers. There is strong evidence for a chemoprotective effect of vitamin A in bladder cancer. The authors recommend 32,000 IU/day of vitamin A initially, with lower doses (24,000 IU) for persons less than 50 kg. Because liver toxicity is a

  4. Genetics Home Reference: bladder cancer

    MedlinePlus

    ... SA, James ND, Jankowski JA, Wallace DM. Molecular pathways in bladder cancer: part 1. BJU Int. 2005 Mar;95(4): ... SA, James ND, Jankowski JA, Wallace DM. Molecular pathways in bladder cancer: part 2. BJU Int. 2005 Mar;95(4): ...

  5. Drugs Approved for Bladder Cancer

    Cancer.gov

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

  6. Urology and nephrology update: bladder and kidney cancer.

    PubMed

    Fiore, David C; Fox, Cara-Louise

    2014-01-01

    It has been estimated that bladder and kidney cancers would be diagnosed in approximately 140,000 Americans in 2013, with approximately 30,000 dying from these cancers. Urinary tract cancers affect men more commonly than they do women, and the median age at diagnosis is 65 years. Major risk factors for these cancers include tobacco smoking, certain chemical exposures, family history, age, and obesity. Unexplained hematuria in adults should be evaluated to exclude bladder and kidney cancer. Staging of bladder and kidney cancer should be based on the TNM staging system, which, along with tumor grade, provides important treatment and prognostic information. Urothelial cell carcinoma is the most common type of bladder cancer; it also can occur in the kidneys or ureters. Renal cell carcinoma is the most common type of kidney cancer. Treatment options for bladder cancer vary widely, depending on the grade of the cancer. Early non-muscle-invasive bladder cancer may be removed cystoscopically and/or treated with intravesical immunotherapy or chemotherapy, whereas patients with muscle-invasive bladder tumors typically require surgery. Management of kidney cancer is almost always surgical, unless the patient is too ill to undergo surgery or chooses palliative care.

  7. Bladder cancer epidemiology and genetic susceptibility

    PubMed Central

    Chu, Haiyan; Wang, Meilin; Zhang, Zhengdong

    2013-01-01

    Bladder cancer is the most common malignancy of the urinary system. The incidence of bladder cancer of men is higher than that of women (approximately 4:1). Here, we summarize the bladder cancer-related risk factors, including environmental and genetic factors. In recent years, although the mortality rate induced by bladder cancer has been stable or decreased gradually, the public health effect may be pronounced. The well-established risk factors for bladder cancer are cigarette smoking and occupational exposure. Genetic factors also play important roles in the susceptibility to bladder cancer. A recent study demonstrated that hereditary non-polyposis colorectal cancer is associated with increased risk of bladder cancer. Since 2008, genome-wide association study (GWAS) has been used to identify the susceptibility loci for bladder cancer. Further gene-gene or gene-environment interaction studies need to be conducted to provide more information for the etiology of bladder cancer. PMID:23720672

  8. Treatment of bladder cancer. Oncology overview

    SciTech Connect

    Not Available

    1982-10-01

    Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Surgical treatment of common bladder cancers; Radiation therapy of common bladder cancers; Chemotherapy of common bladder cancers; Immunotherapy of common bladder cancers; Multimodal treatment of common bladder cancers; Other treatment modalities of common bladder cancers; Treatment of less common bladder cancers; Reviews of treatment of bladder cancers.

  9. Bladder Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing bladder cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  10. [Occupational hazards and bladder cancer].

    PubMed

    Nizamova, R S

    1991-01-01

    Occupational exposure to health hazards was studied in 258 industrial workers who had developed cancer of the bladder against 454 matched controls. All the test subjects and controls were residents of the Tambov Province centers of chemical industry. Statistical significance (relative risk-4.7) was established for exposure to aromatic amines. For those contacting with aniline dyes the relative risk (RR) made up 2.4. The risk to develop bladder cancer in powder shops (RR-3.2) was attributed to the hazards of dyes and diphenylamine. In leather-shoe and textile industry the exposure to dyes was not safe (RR-6.1), neither was it to chemicals, oil products, pesticides, overheating (RR-3.2, 1.6, 3.2 and 2.9, respectively). It is stated that in line with a significant risk to develop bladder cancer at exposure to aromatic amines there exist a number of occupational factors contributing to this risk.

  11. Circulating Biomarkers in Bladder Cancer

    PubMed Central

    Nandagopal, Lakshminarayanan; Sonpavde, Guru

    2016-01-01

    Bladder cancer is a molecularly heterogeneous disease characterized by multiple unmet needs in the realm of diagnosis, clinical staging, monitoring and therapy. There is an urgent need to develop precision medicine for advanced urothelial carcinoma. Given the difficulty of serial analyses of metastatic tumor tissue to identify resistance and new therapeutic targets, development of non-invasive monitoring using circulating molecular biomarkers is critically important. Although the development of circulating biomarkers for the management of bladder cancer is in its infancy and may currently suffer from lower sensitivity of detection, they have inherent advantages owing to non-invasiveness. Additionally, circulating molecular alterations may capture tumor heterogeneity without the sampling bias of tissue biopsy. This review describes the accumulating data to support further development of circulating biomarkers including circulating tumor cells, cell-free circulating tumor (ct)-DNA, RNA, micro-RNA and proteomics to improve the management of bladder cancer. PMID:28035318

  12. Gene expression profiling in bladder cancer identifies potential therapeutic targets

    PubMed Central

    Hussain, Syed A.; Palmer, Daniel H.; Syn, Wing-Kin; Sacco, Joseph J.; Greensmith, Richard M.D.; Elmetwali, Taha; Aachi, Vijay; Lloyd, Bryony H.; Jithesh, Puthen V.; Arrand, John; Barton, Darren; Ansari, Jawaher; Sibson, D. Ross; James, Nicholas D.

    2017-01-01

    Despite advances in management, bladder cancer remains a major cause of cancer related complications. Characterisation of gene expression patterns in bladder cancer allows the identification of pathways involved in its pathogenesis, and may stimulate the development of novel therapies targeting these pathways. Between 2004 and 2005, cystoscopic bladder biopsies were obtained from 19 patients and 11 controls. These were subjected to whole transcript-based microarray analysis. Unsupervised hierarchical clustering was used to identify samples with similar expression profiles. Hypergeometric analysis was used to identify canonical pathways and curated networks having statistically significant enrichment of differentially expressed genes. Osteopontin (OPN) expression was validated by immunohistochemistry. Hierarchical clustering defined signatures, which differentiated between cancer and healthy tissue, muscle-invasive or non-muscle invasive cancer and healthy tissue, grade 1 and grade 3. Pathways associated with cell cycle and proliferation were markedly upregulated in muscle-invasive and grade 3 cancers. Genes associated with the classical complement pathway were downregulated in non-muscle invasive cancer. Osteopontin was markedly overexpressed in invasive cancer compared to healthy tissue. The present study contributes to a growing body of work on gene expression signatures in bladder cancer. The data support an important role for osteopontin in bladder cancer, and identify several pathways worthy of further investigation. PMID:28259975

  13. Urinary markers for bladder cancer

    PubMed Central

    Smith, Zachary L.

    2013-01-01

    Bladder cancer has the fifth highest incidence of all malignancies in the United States, with a propensity to recur, requiring lifelong surveillance after diagnosis. Urinary markers of disease have been of extreme interest in this field in an effort to simplify surveillance schedules and improve early detection of tumors. Many markers have been described, but most remain investigational. However, some markers have undergone clinical trials and are approved for clinical use. In this review, urinary markers and their application for screening and surveillance of bladder cancer are discussed. PMID:23864929

  14. Pathobiology and Chemoprevention of Bladder Cancer

    PubMed Central

    Tanaka, Takuji; Miyazawa, Katsuhito; Tsukamoto, Tetsuya; Kuno, Toshiya; Suzuki, Koji

    2011-01-01

    Our understanding of the pathogenesis of bladder cancer has improved considerably over the past decade. Translating these novel pathobiological discoveries into therapies, prevention, or strategies to manage patients who are suspected to have or who have been diagnosed with bladder cancer is the ultimate goal. In particular, the chemoprevention of bladder cancer development is important, since urothelial cancer frequently recurs, even if the primary cancer is completely removed. The numerous alterations of both oncogenes and tumor suppressor genes that have been implicated in bladder carcinogenesis represent novel targets for therapy and prevention. In addition, knowledge about these genetic alterations will help provide a better understanding of the biological significance of preneoplastic lesions of bladder cancer. Animal models for investigating bladder cancer development and prevention can also be developed based on these alterations. This paper summarizes the results of recent preclinical and clinical chemoprevention studies and discusses screening for bladder cancer. PMID:21941546

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

    PubMed

    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.

  16. Molecular pathology and biomarkers of bladder cancer.

    PubMed

    Czerniak, Bogdan

    2010-01-01

    Bladder cancer originates in the epithelial lining of the bladder's mucosa and develops in association with several habitual, industrial, and environmental risk factors via papillary and non-papillary pathways. In this chapter we review novel concepts concerning the molecular mechanisms of early field change in bladder neoplasia stemming from whole-organ genomic mapping studies. These mechanisms are discussed in the context of molecular pathogenesis of bladder cancer and in relation to treatment and biomarker-based detection strategies.

  17. [The latest news on bladder cancer].

    PubMed

    Retz, M; Lehmann, J; Nawroth, R; Gschwend, J E

    2007-07-01

    A review of the current literature provides new scientific insights into the diagnosis, prognosis and novel molecular targets for bladder cancer. The new WHO classification refines our staging system and influences treatment options. International clinical databases provide new tools for calculating the individual risk for bladder cancer recurrence and progression. Systematic gene cluster analysis defines multimarker panels that can serve as robust predictors of outcome. Discoveries of new signaling pathways in bladder cancer are leading to novel molecular targets for innovative therapies.

  18. CMTM8 inhibits the carcinogenesis and progression of bladder cancer

    PubMed Central

    GAO, DENGHUI; HU, HAO; WANG, YING; YU, WEIDONG; ZHOU, JIANHUA; WANG, XIAOFENG; WANG, WEIPING; ZHOU, CHUNYAN; XU, KEXIN

    2015-01-01

    Bladder cancer is the most common tumor of the urinary tract. The incidence of bladder cancer has increased in the last few decades, thus novel molecular markers for early diagnosis and more efficacious treatment are urgently needed. Chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing 8 (CMTM8) is downregulated in several types of cancers and is associated with tumor progression. However, CMTM8 expression has been unexplored in bladder cancer to date. Our results revealed that the expression of CMTM8 was negative in 46 of 74 (62.2%) bladder cancer samples via immunohistochemistry assay. CMTM8 downregulation was associated with advancing tumor stage and tumor grade. CMTM8 was successfully overexpressed by lentivirus in EJ and T24 cells, and the CCK-8 and Transwell assays showed that CMTM8 overexpression decreased cell proliferation, migration and invasion in vitro. In tumor xenografts upregulation of CMTM8 inhibited tumor growth and lymph node metastasis in vivo. In conclusion, overexpression of CMTM8 in bladder cancer results in reduced malignant cell growth, migration and invasion, which could make it a potential therapeutic target in the treatment of bladder cancer. PMID:26503336

  19. Spectroscopic Imaging of Bladder Cancer

    SciTech Connect

    Demos, S G; Gandour-Edwards, R; Ramsamooj, R; deVere White, R

    2003-01-01

    The feasibility of developing bladder cancer detection methods using intrinsic tissue optical properties is the focus of this investigation. In vitro experiments have been performed using polarized elastic light scattering in combination with tissue autofluorescence in the NIR spectral region under laser excitation in the green and red spectral regions. The experimental results obtained from a set of tissue specimens from 25 patients reveal the presence of optical fingerprint characteristics suitable for cancer detection with high contrast and accuracy. These photonic methods are compatible with existing endoscopic imaging modalities which make them suitable for in-vivo application.

  20. The WHO/ISUP 1998 and WHO 1999 systems for malignancy grading of bladder cancer. Scientific foundation and translation to one another and previous systems.

    PubMed

    Busch, Christer; Algaba, Ferran

    2002-08-01

    Recently, two new classification systems for grading of urothelial neoplasms have been published. The objective of both was to avoid the overdiagnosis of cancer and to create better criteria for the grades. The WHO/ISUP classification of 1998 distinguishes papilloma, papillary urothelial neoplasm of low malignant potential (PUNLMP), low and high grade carcinomas, whereas the WHO 1999 system subdivides the high grade into grades II and III, and is otherwise identical. This note summarizes studies supporting the rationale of the two new systems, describes pattern recognition criteria for the grades, and highlights the homology between them.

  1. Bladder cancer documentation of causes: multilingual questionnaire, 'bladder cancer doc'.

    PubMed

    Golka, Klaus; Abreu-Villaca, Yael; Anbari Attar, Rowshanak; Angeli-Greaves, Miriam; Aslam, Muhammad; Basaran, Nursen; Belik, Rouslana; Butryee, Chaniphun; Dalpiaz, Orietta; Dzhusupov, Keneshbek; Ecke, Thorsten H; Galambos, Henrieta; Galambos, Henrieta; Gerilovica, Helena; Gerullis, Holger; Gonzalez, Patricia Casares; Goossens, Maria E; Gorgishvili-Hermes, Lela; Heyns, Chris F; Hodzic, Jasmin; Ikoma, Fumihiko; Jichlinski, Patrice; Kang, Boo-Hyon; Kiesswetter, Ernst; Krishnamurthi, Kannan; Lehmann, Marie-Louise; Martinova, Irina; Mittal, Rama Devi; Ravichandran, Beerappa; Romics, Imre; Roy, Bidyut; Rungkat-Zakaria, Fransiska; Rydzynski, Konrad; Scutaru, Cristian; Shen, Jianhua; Soufi, Maria; Toguzbaeva, Karlygash; Vu Duc, Trinh; Widera, Agata; Wishahi, Mohamed; Hengstler, Jan G

    2012-06-01

    There is a considerable discrepancy between the number of identified occupational-related bladder cancer cases and the estimated numbers particularly in emerging nations or less developed countries where suitable approaches are less or even not known. Thus, within a project of the World Health Organisation Collaborating Centres in Occupational Health, a questionnaire of the Dortmund group, applied in different studies, was translated into more than 30 languages (Afrikaans, Arabic, Bengali, Chinese, Czech, Dutch, English, Finnish, French, Georgian, German, Greek, Hindi, Hungarian, Indonesian, Italian, Japanese, Kannada, Kazakh, Kirghiz, Korean, Latvian, Malay, Persian (Farsi), Polish, Portuguese, Portuguese/Brazilian, Romanian, Russian, Serbo-Croatian, Slovak, Spanish, Spanish/Mexican, Tamil, Telugu, Thai, Turkish, Urdu, Vietnamese). The bipartite questionnaire asks for relevant medical information in the physician's part and for the occupational history since leaving school in the patient's part. Furthermore, this questionnaire is asking for intensity and frequency of certain occupational and non-occupational risk factors. The literature regarding occupations like painter, hairdresser or miner and exposures like carcinogenic aromatic amines, azo dyes, or combustion products is highlighted. The questionnaire is available on www.ifado.de/BladderCancerDoc.

  2. CEUS in the differentiation between low and high-grade bladder carcinoma

    PubMed Central

    Drudi, F.M.; Di Leo, N.; Malpassini, F.; Antonini, F.; Corongiu, E.; Iori, F.

    2012-01-01

    Introduction Bladder cancer ranks 4th overall in the number of newly diagnosed cancers and 10th in causes of cancer deaths. More than 90% of all cases of bladder cancer are transitional cell carcinoma (TCC). The goal of this study is to confirm the usefulness of low mechanical index contrast-enhanced ultrasonography (CEUS), also in association with time–intensity curves, in the differentiation between high- and low-grade bladder malignant lesions. Materials and methods From February 2006 to February 2012 we recruited 144 patients. All patients underwent grayscale ultrasonography (US), color-Doppler ultrasonography (CDUS) and contrast-enhanced ultrasonography (CEUS). Subsequently all patients underwent cystoscopy and TURB. Results Histological diagnoses were: 88 high-grade carcinomas (61.1%), and 56 low-grade carcinomas (38.9%). Sensitivity and specificity of CDUS were 87.5% (126/144) and 60%, respectively. Sensitivity and specificity of CEUS were 90.9% and 85.7%, respectively. Sensitivity and specificity of TIC were 91.6% (132/144) and 85.7%, respectively. Discussion and conclusions CEUS is a reliable noninvasive method for differentiating low- and high-grade bladder carcinomas since it provides typical enhancement patterns as well as specific contrast-sonographic perfusion curves. PMID:23730389

  3. Neoadjuvant chemotherapy for bladder cancer.

    PubMed

    Black, Peter C; Brown, Gordon A; Grossman, H Barton; Dinney, Colin P

    2006-11-01

    The 30-45% failure rate after radical cystoprostatectomy mandates that we explore and optimize multimodal therapy to achieve better disease control in these patients. Cisplatin-based multi-agent combination chemotherapy has been used with success in metastatic disease and has therefore also been introduced in patients with high-risk but non-metastatic bladder cancer. There is now convincing evidence that chemotherapy given pre-operatively can improve survival in these patients. In this review we establish the need for peri-operative chemotherapy in bladder cancer patients and summarize the evidence for the efficacy of neoadjuvant chemotherapy. The advantages and disadvantages of neoadjuvant versus adjuvant chemotherapy are discussed, and the main shortcomings of both--treatment-related toxicity and the inability to prospectively identify likely responders--are presented. Finally, a risk-adapted approach to neoadjuvant chemotherapy is presented, whereby the highest risk patients are offered treatment while those unlikely to benefit are spared the treatment-related toxicity.

  4. Detection of Bladder Cancer Using Proteomic Profiling of Urine Sediments

    PubMed Central

    Majewski, Tadeusz; Spiess, Philippe E.; Bondaruk, Jolanta; Black, Peter; Clarke, Charlotte; Benedict, William; Dinney, Colin P.; Grossman, Herbert Barton; Tang, Kuang S.; Czerniak, Bogdan

    2012-01-01

    We used protein expression profiles to develop a classification rule for the detection and prognostic assessment of bladder cancer in voided urine samples. Using the Ciphergen PBS II ProteinChip Reader, we analyzed the protein profiles of 18 pairs of samples of bladder tumor and adjacent urothelium tissue, a training set of 85 voided urine samples (32 controls and 53 bladder cancer), and a blinded testing set of 68 voided urine samples (33 controls and 35 bladder cancer). Using t-tests, we identified 473 peaks showing significant differential expression across different categories of paired bladder tumor and adjacent urothelial samples compared to normal urothelium. Then the intensities of those 473 peaks were examined in a training set of voided urine samples. Using this approach, we identified 41 protein peaks that were differentially expressed in both sets of samples. The expression pattern of the 41 protein peaks was used to classify the voided urine samples as malignant or benign. This approach yielded a sensitivity and specificity of 59% and 90%, respectively, on the training set and 80% and 100%, respectively, on the testing set. The proteomic classification rule performed with similar accuracy in low- and high-grade bladder carcinomas. In addition, we used hierarchical clustering with all 473 protein peaks on 65 benign voided urine samples, 88 samples from patients with clinically evident bladder cancer, and 127 samples from patients with a history of bladder cancer to classify the samples into Cluster A or B. The tumors in Cluster B were characterized by clinically aggressive behavior with significantly shorter metastasis-free and disease-specific survival. PMID:22879988

  5. Detection of bladder cancer using proteomic profiling of urine sediments.

    PubMed

    Majewski, Tadeusz; Spiess, Philippe E; Bondaruk, Jolanta; Black, Peter; Clarke, Charlotte; Benedict, William; Dinney, Colin P; Grossman, Herbert Barton; Tang, Kuang S; Czerniak, Bogdan

    2012-01-01

    We used protein expression profiles to develop a classification rule for the detection and prognostic assessment of bladder cancer in voided urine samples. Using the Ciphergen PBS II ProteinChip Reader, we analyzed the protein profiles of 18 pairs of samples of bladder tumor and adjacent urothelium tissue, a training set of 85 voided urine samples (32 controls and 53 bladder cancer), and a blinded testing set of 68 voided urine samples (33 controls and 35 bladder cancer). Using t-tests, we identified 473 peaks showing significant differential expression across different categories of paired bladder tumor and adjacent urothelial samples compared to normal urothelium. Then the intensities of those 473 peaks were examined in a training set of voided urine samples. Using this approach, we identified 41 protein peaks that were differentially expressed in both sets of samples. The expression pattern of the 41 protein peaks was used to classify the voided urine samples as malignant or benign. This approach yielded a sensitivity and specificity of 59% and 90%, respectively, on the training set and 80% and 100%, respectively, on the testing set. The proteomic classification rule performed with similar accuracy in low- and high-grade bladder carcinomas. In addition, we used hierarchical clustering with all 473 protein peaks on 65 benign voided urine samples, 88 samples from patients with clinically evident bladder cancer, and 127 samples from patients with a history of bladder cancer to classify the samples into Cluster A or B. The tumors in Cluster B were characterized by clinically aggressive behavior with significantly shorter metastasis-free and disease-specific survival.

  6. The Danish Bladder Cancer Database

    PubMed Central

    Hansen, Erik; Larsson, Heidi; Nørgaard, Mette; Thind, Peter; Jensen, Jørgen Bjerggaard

    2016-01-01

    Aim of database The aim of the Danish Bladder Cancer Database (DaBlaCa-data) is to monitor the treatment of all patients diagnosed with invasive bladder cancer (BC) in Denmark. Study population All patients diagnosed with BC in Denmark from 2012 onward were included in the study. Results presented in this paper are predominantly from the 2013 population. Main variables In 2013, 970 patients were diagnosed with BC in Denmark and were included in a preliminary report from the database. A total of 458 (47%) patients were diagnosed with non-muscle-invasive BC (non-MIBC) and 512 (53%) were diagnosed with muscle-invasive BC (MIBC). A total of 300 (31%) patients underwent cystectomy. Among the 135 patients diagnosed with MIBC, who were 75 years of age or younger, 67 (50%) received neoadjuvent chemotherapy prior to cystectomy. In 2013, a total of 147 patients were treated with curative-intended radiation therapy. Descriptive data One-year mortality was 28% (95% confidence interval [CI]: 15–21). One-year cancer-specific mortality was 25% (95% CI: 22–27%). One-year mortality after cystectomy was 14% (95% CI: 10–18). Ninety-day mortality after cystectomy was 3% (95% CI: 1–5) in 2013. One-year mortality following curative-intended radiation therapy was 32% (95% CI: 24–39) and 1-year cancer-specific mortality was 23% (95% CI: 16–31) in 2013. Conclusion This preliminary DaBlaCa-data report showed that the treatment of MIBC in Denmark overall meet high international academic standards. The database is able to identify Danish BC patients and monitor treatment and mortality. In the future, DaBlaCa-data will be a valuable data source and expansive observational studies on BC will be available. PMID:27822081

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

    ClinicalTrials.gov

    2016-06-09

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

  8. Photodynamic management of bladder cancer

    NASA Astrophysics Data System (ADS)

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

    2009-06-01

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

  9. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer.

    PubMed

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim; Millikan, Randall E; Stadler, Walter; De Mulder, Pieter; Sherif, Amir; von der Maase, Hans; Tsukamoto, Taiji; Soloway, Mark S

    2007-01-01

    To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed, as is chemotherapy for patients with metastatic urothelial cancer. The conference panel consisted of 10 medical oncologists and urologists from 3 continents who are experts in this field and who reviewed the English-language literature through October 2004. Relevant English-language literature was identified with the use of Medline; additional cited works not detected on the initial search regarding neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and chemotherapy for patients with metastatic urothelial cancer were reviewed. Evidence-based recommendations for diagnosis and management of the disease were made with reference to a 4-point scale. Results of the authors' deliberations are presented as a consensus document. Meta-analysis of randomized trials on cisplatin-containing combination neoadjuvant chemotherapy revealed a 5% difference in favor of neoadjuvant chemotherapy. No randomized trials have yet compared survival with transurethral resection of bladder tumor alone versus cystectomy for the management of patients with muscle-invasive disease. Collaborative international adjuvant chemotherapy trials are needed to assist researchers in assessing the true value of adjuvant chemotherapy. Systemic cisplatin-based combination chemotherapy is the only current modality that has been shown in phase 3 trials to improve survival in responsive patients

  10. Current therapeutic strategies for invasive and metastatic bladder cancer

    PubMed Central

    Vishnu, Prakash; Mathew, Jacob; Tan, Winston W

    2011-01-01

    Background Bladder cancer is one of the most common cancers in Europe, the United States, and Northern African countries. Muscle-invasive bladder cancer is an aggressive epithelial tumor, with a high rate of early systemic dissemination. Superficial, noninvasive bladder cancer can most often be cured; a good proportion of invasive cases can also be cured by a combined modality approach of surgery, chemotherapy, and radiation. Recurrences are common and mostly manifest as metastatic disease. Those with distant metastatic disease can sometime achieve partial or complete remission with combination chemotherapy. Recent developments Better understanding of the biology of the disease has led to the incorporation of molecular and genetic features along with factors such as tumor grade, lympho-vascular invasion, and aberrant histology, thereby allowing identification of ‘favorable’ and ‘unfavorable’ cancers which helps a more accurate informed and objective selection of patients who would benefit from neoadjuvant and adjuvant chemotherapy. Gene expression profiling has been used to find molecular signature patterns that can potentially be predictive of drug sensitivity and metastasis. Understanding the molecular pathways of invasive bladder cancer has led to clinical investigation of several targeted therapeutics such as anti-angiogenics, mTOR inhibitors, and anti-EGFR agents. Conclusion With improvements in the understanding of the biology of bladder cancer, clinical trials studying novel and targeted agents alone or in combination with chemotherapy have increased the armamentarium for the treatment of bladder cancer. Although the novel biomarkers and gene expression profiles have been shown to provide important predictive and prognostic information and are anticipated to be incorporated in clinical decision-making, their exact utility and relevance calls for a larger prospective validation. PMID:21792316

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

    PubMed Central

    Yang, Ganglong; Xu, Zhipeng; Lu, Wei; Li, Xiang; Sun, Chengwen; Guo, Jia; Xue, Peng; Guan, Feng

    2015-01-01

    The best way to increase patient survival rate is to identify patients who are likely to progress to muscle-invasive or metastatic disease upfront and treat them more aggressively. The human cell lines HCV29 (normal bladder epithelia), KK47 (low grade nonmuscle invasive bladder cancer, NMIBC), and YTS1 (metastatic bladder cancer) have been widely used in studies of molecular mechanisms and cell signaling during bladder cancer (BC) progression. However, little attention has been paid to global quantitative proteome analysis of these three cell lines. We labeled HCV29, KK47, and YTS1 cells by the SILAC method using three stable isotopes each of arginine and lysine. Labeled proteins were analyzed by 2D ultrahigh-resolution liquid chromatography LTQ Orbitrap mass spectrometry. Among 3721 unique identified and annotated proteins in KK47 and YTS1 cells, 36 were significantly upregulated and 74 were significantly downregulated with >95% confidence. Differential expression of these proteins was confirmed by western blotting, quantitative RT-PCR, and cell staining with specific antibodies. Gene ontology (GO) term and pathway analysis indicated that the differentially regulated proteins were involved in DNA replication and molecular transport, cell growth and proliferation, cellular movement, immune cell trafficking, and cell death and survival. These proteins and the advanced proteome techniques described here will be useful for further elucidation of molecular mechanisms in BC and other types of cancer. PMID:26230496

  12. Prognostic significance of selected lifestyle factors in urinary bladder cancer.

    PubMed

    Wakai, K; Ohno, Y; Obata, K; Aoki, K

    1993-12-01

    To examine the prognostic significance of lifestyle factors in urinary bladder cancer, we conducted a follow-up study of 258 incident bladder cancer patients, who were originally recruited in a case-control study in metropolitan Nagoya. Information on individual survivals was obtained from the computer data-file of the tumor registry of the Nagoya Bladder Cancer Research Group. Univariate analyses revealed significant associations of 5-year survivorship with educational attainment, marital status, drinking habits and consumption of green tea in males, and age at first consultation, histological type and grade of tumor, stage and distant metastasis in both sexes. After adjustment for age, stage, histology (histological type and grade) and distant metastasis by means of a proportional hazards model, drinking of alcoholic beverages was significantly associated with the prognosis of bladder cancer in males. Its adjusted hazard ratio was 0.46 (95% confidence interval: 0.26-0.79), favoring patients who had taken alcoholic beverages. In detailed analysis, ex-drinkers and all levels of current drinkers demonstrated hazard ratios smaller than unity, although no clear dose-response relationship was detected. No prognostic significance was found for such lifestyle factors as smoking habit, uses of artificial sweeteners and hairdye, and consumption of coffee, black tea, matcha (powdered green tea) and cola.

  13. Gemcitabine, Paclitaxel, Doxorubicin in Metastatic or Unresectable Bladder Cancer With Decreased Kidney Function

    ClinicalTrials.gov

    2015-06-19

    Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer

  14. Accuracy and Readability of Websites on Kidney and Bladder Cancers.

    PubMed

    Azer, Samy A; Alghofaili, Maha M; Alsultan, Rana M; Alrumaih, Najla S

    2017-03-09

    The aim of this study was to assess the scientific accuracy and the readability level of websites on kidney and bladder cancers. The search engines Google™, Yahoo™ and Bing™ were searched independently by assessors in November 2014 using the following keywords: "bladder cancer", "kidney cancer", "patient bladder cancer", "patient kidney cancer" and "bladder and kidney cancer". Only English-language websites were selected on the bases of predetermined inclusion and exclusion criteria. Assessors independently reviewed the findings and evaluated the accuracy and quality of each website by using the DISCERN and the LIDA instruments. The readability of the websites was calculated using the Flesch-Kincaid Grade Level Index and the Coleman-Liau Readability Index. Sixty-two websites were finally included in the study. The overall accuracy scores varied; for the DISCERN, the range was 28 to 76; out of 80 (mean ± SD, 47.1 ± 12.1; median = 46.0, interquartile range (IQR) = 19.2), and for the LIDA, the range was 52 to 125; out of 144 (mean ± SD, 101.9 ± 15.2; median, 103; IQR, 16.5). The creators of these websites were universities and research centres (n = 25, 40%), foundations and associations (n = 10, 16%), commercial and pharmaceutical companies (n = 13, 21%), charities and volunteer work (n = 4, 6%) and non-university educational bodies (n = 10, 16%). The readability scores (mean ± SD) were 11.2 ± 2.2 for the Flesch-Kincaid Grade Level Index and 11.2 ± 1.6 for the Coleman-Liau Readability Index. The accuracy and the quality of the websites on kidney and bladder cancers varied. In most websites, there were deficiencies in clarity of aims, presenting symptoms, investigations and treatment options. The readability matched grades 10-11 literacy levels-a level above the public readability level. The study highlights the needs for further improvement of the online information created for public and patients with kidney and bladder

  15. [Grading of prostate cancer].

    PubMed

    Kristiansen, G; Roth, W; Helpap, B

    2016-07-01

    The current grading of prostate cancer is based on the classification system of the International Society of Urological Pathology (ISUP) following a consensus conference in Chicago in 2014. The foundations are based on the frequently modified grading system of Gleason. This article presents a brief description of the development to the current ISUP grading system.

  16. Glucocorticoid therapy and risk of bladder cancer

    PubMed Central

    Dietrich, K; Schned, A; Fortuny, J; Heaney, J; Marsit, C; Kelsey, K T; Karagas, M R

    2009-01-01

    Background: Use of immunosuppressive drugs post organ transplantation, and prolonged use of glucorticoids for other conditions have been associated with subsequent risk of certain malignancies, that is, skin cancers and lymphoma. There is evidence that the incidence of bladder cancer is also elevated among organ transplant recipients, however, it is unknown whether other groups of patients, that is, those taking oral glucocorticoids, likewise are at an increased risk. Methods: In a population-based case–control study in New Hampshire, USA, we compared the use of glucocorticoids in 786 bladder cancer cases and in 1083 controls. We used unconditional logistic regression analysis to compute adjusted odds ratios (ORs) associated with oral glucocorticoid use. Results: In our analysis, the risk of bladder cancer was related to a history of prolonged oral glucocorticoid use (OR=1.85, 95% CI=1.24–2.76, adjusted for age, gender and smoking). Associations with oral glucocorticoid use were stronger for invasive tumours (OR=2.12, 95% CI=1.17–3.85) and tumours with high (3+) p53 staining intensity (OR=2.35, 95% CI=1.26–4.36). Conclusion: Our results raise the possibility of an increased risk of bladder cancer from systemic use of glucocorticoids, and a potential role of immune surveillance in bladder cancer aetiology. PMID:19773763

  17. RECURRENCE OF HIGH-RISK BLADDER CANCER: A POPULATION-BASED ANALYSIS

    PubMed Central

    Chamie, Karim; Litwin, Mark S.; Bassett, Jeffrey C.; Daskivich, Timothy J.; Lai, Julie; Hanley, Jan M.; Konety, Badrinath R.; Saigal, Christopher S.

    2013-01-01

    Background Patients with bladder cancer are apt to develop multiple recurrences that require intervention. We examined the recurrence, progression and bladder cancer-related mortality rates in a cohort of individuals with high-grade non-muscle-invasive bladder cancer. Methods Using linked SEER-Medicare data, we identified subjects with a diagnosis of high-grade, non-muscle-invasive disease in 1992–2002 and were followed until 2007. We then used multivariate competing-risks regression analyses to examine recurrence, progression, and bladder cancer-related mortality rates. Results Of 7,410 subjects, 2,897 (39.1%) experienced a recurrence without progression, 2,449 (33.0%) experienced disease progression, of whom 981 succumbed to bladder cancer. Using competing-risks regression analysis, we found the 10-year recurrence, progression, and bladder cancer-related mortality rates to be 74.3%, 33.3%, and 12.3%, respectively. Stage T1 was the only variable associated with a higher rate of recurrence. Women, black race, undifferentiated grade, stage Tis and T1 were associated with a higher risk of progression and mortality. Advanced age (≥70) was associated with a higher risk of bladder cancer-related mortality. Conclusions Nearly three-fourths of patients diagnosed with high-risk bladder cancer will recur, progress, or die within ten years of their diagnosis. Even though most patients do not die of bladder cancer, the vast majority endures the morbidity of recurrence and progression of their cancer. Increasing efforts should be made to offer patients intravesical therapy with the goal of minimizing the incidence of recurrences. Furthermore, the high recurrence rate seen during the first two years of diagnosis warrants an intense surveillance schedule. PMID:23737352

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

    PubMed Central

    Ambrose, Sarah R.; Gordon, Naheema S.; Goldsmith, James C.; Wei, Wenbin; Zeegers, Maurice P.; James, Nicholas D.; Knowles, Margaret A.; Bryan, Richard T.; Ward, Douglas G.

    2015-01-01

    Developing a urine test to detect bladder tumours with high sensitivity and specificity is a key goal in bladder cancer research. We hypothesised that bladder cancer-specific glycoproteins might fulfill this role. Lectin-ELISAs were used to study the binding of 25 lectins to 10 bladder cell lines and serum and urine from bladder cancer patients and non-cancer controls. Selected lectins were then used to enrich glycoproteins from the urine of bladder cancer patients and control subjects for analysis by shotgun proteomics. None of the lectins showed a strong preference for bladder cancer cell lines over normal urothlelial cell lines or for urinary glycans from bladder cancer patients over those from non-cancer controls. However, several lectins showed a strong preference for bladder cell line glycans over serum glycans and are potentially useful for enriching glycoproteins originating from the urothelium in urine. Aleuria alantia lectin affinity chromatography and shotgun proteomics identified mucin-1 and golgi apparatus protein 1 as proteins warranting further investigation as urinary biomarkers for low-grade bladder cancer. Glycosylation changes in bladder cancer are not reliably detected by measuring lectin binding to unfractionated proteomes, but it is possible that more specific reagents and/or a focus on individual proteins may produce clinically useful biomarkers. PMID:28248271

  19. Relationship between Schistosomiasis and Bladder Cancer

    PubMed Central

    Mostafa, M. H.; Sheweita, S. A.; O’Connor, P. J.

    1999-01-01

    Carcinoma of the urinary bladder is the most common malignancy in the Middle East and parts of Africa where schistosomiasis is a widespread problem. Much evidence supports the association between schistosomiasis and bladder cancer: this includes the geographical correlation between the two conditions, the distinctive patterns of gender and age at diagnosis, the clinicopathological identity of schistosome-associated bladder cancer, and extensive evidence in experimentally infected animals. Multiple factors have been suggested as causative agents in schistosome-associated bladder carcinogenesis. Of these, N-nitroso compounds appear to be of particular importance since they were found at high levels in the urine of patients with schistosomiasis-associated bladder cancer. Various strains of bacteria that can mediate nitrosation reactions leading to the formation of N-nitrosamines have been identified in the urine of subjects with schistosomiasis at higher intensities of infection than in normal subjects. In experimental schistosomiasis, the activities of carcinogen-metabolizing enzymes are increased soon after infection but are reduced again during the later chronic stages of the disease. Not only could this prolong the period of exposure to activated N-nitrosamines, but also inflammatory cells, sitmulated as a result of the infection, may induce the endogenous synthesis of N-nitrosamines as well as generating oxygen radicals. Higher than normal levels of host cell DNA damage are therefore anticipated, and they have indeed been observed in the case of alkylation damage, together with an inefficiency in the capacity of relevant enzymes to repair this damaged DNA. In experimental schistosomiasis, it was also found that endogenous levels of host cell DNA damage were related to the intensity of infection. All of these factors could contribute to an increased risk of bladder cancer in patients with schistosomiasis, and in particular, the gene changes observed may have

  20. Elevated matrix metalloproteinase-9 expression may contribute to the pathogenesis of bladder cancer

    PubMed Central

    ZENG, FAN-CHANG; CEN, SONG; TANG, ZHENG-YAN; KANG, XIN-LI

    2016-01-01

    The present study investigated the potential association between matrix metalloproteinase-9 (MMP-9) expression and the pathogenesis of bladder cancer. The present study reviewed previous studies published in Chinese and English using predefined selection criteria, which identified high-quality studies concerning MMP-9 and bladder cancer. Statistical analyses of the data were conducted using Comprehensive Meta-Analysis software version 2.0. In total, 23 case-control studies were selected, which consisted of 1,040 bladder cancer patients and 244 healthy controls. The expression rates and protein levels of MMP-9 were significantly increased in bladder cancer patients compared with the healthy controls, which was demonstrated using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay-based methods. Furthermore, the expression rate of MMP-9 in histological G1/G2 grade bladder cancer tumors was significantly decreased compared with G3 tumors. Subgroup analysis based on ethnicity demonstrated that the rate of MMP-9 protein expression between bladder cancer patients and healthy controls was significantly different in African, Asian and Caucasian patients, which was identified using IHC. The MMP-9 protein levels in bladder cancer patients and healthy controls were significantly different between Asian and Caucasian patients, but not African patients. The differences between MMP-9 expression in ethnic groups were also evident in the expression rate of MMP-9 identified in histological G1/G2 grade tumors in Asian and Caucasian patients compared with G3 grade tumors, which was not evident in African patients. In conclusion, the present meta-analysis results markedly indicate that MMP-9 expression is associated with clinicopathological features of bladder cancer, suggesting that MMP-9 may be a useful biomarker in the diagnosis and clinical management of bladder cancer, and may be a valuable therapeutic target. PMID:26998151

  1. Bladder cancer: smoking, beverages and artificial sweeteners

    PubMed Central

    Morgan, Robert W.; Jain, Meera G.

    1974-01-01

    A matched patient-control study of bladder cancer examined the relationship of the disease to occupation, smoking and intake of tea, coffee, cola, alcohol and artificial sweeteners. There was no association of disease with occupation for these patients. Heavy smoking gave relative risks of 6.37 and 4.36 for men and women respectively; there was evidence of a dose-response relationship. Tea and coffee intake did not increase the risk of disease nor did prolonged use of artificial sweeteners. Alcohol and cola intake increased the relative risk of bladder cancer among male smokers. There is some suggestion that smoking interacts with both alcohol and cola intake in the production of bladder cancer. PMID:4429932

  2. Androgen Receptor Signaling in Bladder Cancer

    PubMed Central

    Li, Peng; Chen, Jinbo; Miyamoto, Hiroshi

    2017-01-01

    Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific differences in bladder cancer. This review summarizes and discusses the available data, suggesting the involvement of androgens and/or the androgen receptor pathways in urothelial carcinogenesis as well as tumor growth. While the precise mechanisms of the functions of the androgen receptor in urothelial cells remain far from being fully understood, current evidence may offer chemopreventive or therapeutic options, using androgen deprivation therapy, in patients with bladder cancer. PMID:28241422

  3. Atezolizumab in Treating Patients With Recurrent BCG-Unresponsive Non-muscle Invasive Bladder Cancer

    ClinicalTrials.gov

    2017-03-30

    Recurrent Bladder Urothelial Carcinoma; Stage 0a Bladder Urothelial Carcinoma; Stage 0is Bladder Urothelial Carcinoma; Stage I Bladder Cancer With Carcinoma In Situ; Stage I Bladder Urothelial Carcinoma

  4. New Optical Imaging Technologies for Bladder Cancer: Considerations and Perspectives

    PubMed Central

    Liu, Jen-Jane; Droller, Michael J.; Liao, Joseph C.

    2014-01-01

    Purpose Bladder cancer presents as a spectrum of different diatheses. Accurate assessment for individualized treatment depends on initial diagnostic accuracy. Detection relies on white light cystoscopy accuracy and comprehensiveness. Aside from invasiveness and potential risks, white light cystoscopy shortcomings include difficult flat lesion detection, precise tumor delineation to enable complete resection, inflammation and malignancy differentiation, and grade and stage determination. Each shortcoming depends on surgeon ability and experience with the technology available for visualization and resection. Fluorescence cystoscopy/photodynamic diagnosis, narrow band imaging, confocal laser endomicroscopy and optical coherence tomography address the limitations and have in vivo feasibility. They detect suspicious lesions (photodynamic diagnosis and narrow band imaging) and further characterize lesions (optical coherence tomography and confocal laser endomicroscopy). We analyzed the added value of each technology beyond white light cystoscopy and evaluated their maturity to alter the cancer course. Materials and Methods Detailed PubMed® searches were done using the terms “fluorescence cystoscopy,” “photodynamic diagnosis,” “narrow band imaging,” “optical coherence tomography” and “confocal laser endomicroscopy” with “optical imaging,” “bladder cancer” and “urothelial carcinoma.” Diagnostic accuracy reports and all prospective studies were selected for analysis. We explored technological principles, preclinical and clinical evidence supporting nonmuscle invasive bladder cancer detection and characterization, and whether improved sensitivity vs specificity translates into improved correlation of diagnostic accuracy with recurrence and progression. Emerging preclinical technologies with potential application were reviewed. Results Photodynamic diagnosis and narrow band imaging improve nonmuscle invasive bladder cancer detection, including

  5. New discoveries in the molecular landscape of bladder cancer

    PubMed Central

    Li, Roger; Choi, Woonyoung; Ferguson 3rd, J.E.; Metcalfe, Michael J.; Kamat, Ashish M.

    2016-01-01

    We are currently on the cusp of exponential growth in the understanding of the molecular landscape of bladder cancer. Emerging data regarding the mutational burden and targetable genomic and protein alterations in bladder cancer have allowed us to tap into treatments directed toward specific molecular characteristics of bladder cancer. In parallel, these developments will enable us to better select patients for existing treatments of bladder cancer in a step toward personalized therapy. The present article reviews select discoveries that have advanced our understanding of bladder cancer and gives a glimpse of the exciting opportunities on the not-so-distant horizon. PMID:28105319

  6. Association between GPX1 Pro189Leu polymorphism and the occurrence of bladder cancer in Morocco.

    PubMed

    Hadami, K; Ameziane El Hassani, R; Ameur, A; Dakka, N; Abbar, M; Al Bouzidi, A; Attaleb, M; El Mzibri, M

    2016-12-30

    Worldwide, Bladder cancer is the most frequent male malignancy. It is the third most common male malignancy in Morocco. The risk factors for developing bladder cancer are multiples including dietary conditions, environmental exposure and oxidative stress. GPX1 gene encoding for the human cellular antioxidant enzyme glutathione peroxidase1 is a key factor in the cell detoxification process. GPX1 Pro198Leu polymorphism is associated with a decrease of enzyme activity and may contribute to bladder cancer susceptibility. The present case-control study was planned to assess the presence of GPX1 Pro198Leu polymorphism in Moroccan population to determine whether it is associated with the risk of developing bladder cancer in Moroccan patients. A total of 32 patients with bladder cancer and 40 healthy controls were enrolled. Genotyping of the GPX1 Pro198Leu polymorphism was carried out by PCR amplification and DNA sequencing. Pro198Leu polymorphism was observed in both bladder cancer patients and healthy controls. No significant association between the polymorphism and bladder cancer occurrence was found (Pro/Leu vs. Pro/Pro: p=0.425; Leu vs. Pro: p=0.435). For the analysis of Pro198Leu polymorphism and progression of bladder cancer, no association was observed neither for stages (Pro/Leu vs. Pro/Pro: p=0.500; Leu vs. Pro: p=0.500) nor grades (Pro/Leu vs. Pro/Pro: p=0.415; Leu vs. Pro: p=0.427). Our results clearly showed no significant association between Pro198Leu polymorphism and risk of bladder cancer in our population, suggesting that the effect of this polymorphism on bladder cancer development might be a result of a combination with other genetic alterations and/or non-genetic variables such as diet and lifestyle factors.

  7. Arsenic and bladder cancer: observations and suggestions.

    PubMed

    Radosavljević, Vladan; Jakovljević, Branko

    2008-10-01

    Arsenic from drinking water is a well-known risk factor for bladder cancer. The purpose of this paper is to systematize some important yet often overlooked facts considering the relationship between arsenic exposure and the occurrence of bladder cancer. Since the exposure to inorganic arsenic from food, inhaled air, and skin absorption as well as arsenic methylation ability are not fully investigated, our assumption is that the exposure of arsenic only from drinking water is underestimated and its role as a risk factor is highly overestimated. This paper proposes some qualitative and quantitative parameters of arsenic as a risk factor for bladder cancer. The recommended qualitative parameters of arsenic intake are first, pathways of exposure, and second, toxicity and metabolism. The suggested quantitative parameters of arsenic intake include amounts of arsenic absorbed in the body, duration of arsenic exposure, and duration of arsenic presence in the urinary bladder. This approach can be implemented in a systematic classification and explanation of various risk factors and their mutual interactions for other types of cancer or diseases in general.

  8. Modeling and simulation of a low-grade urinary bladder carcinoma.

    PubMed

    Bunimovich-Mendrazitsky, Svetlana; Pisarev, Vladimir; Kashdan, Eugene

    2015-03-01

    In this work, we present a mathematical model of the initiation and progression of a low-grade urinary bladder carcinoma. We simulate the crucial processes affecting tumor growth, such as oxygen diffusion, carcinogen penetration, and angiogenesis, within the framework of the urothelial cell dynamics. The cell dynamics are modeled using the discrete technique of cellular automata, while the continuous processes of carcinogen penetration and oxygen diffusion are described by nonlinear diffusion-absorption equations. As the availability of oxygen is necessary for tumor progression, processes of oxygen transport to the tumor growth site seem most important. Our model yields a theoretical insight into the main stages of development and growth of urinary bladder carcinoma with emphasis on the two most common types: bladder polyps and carcinoma in situ. Analysis of histological structure of bladder tumor is important to avoid misdiagnosis and wrong treatment. We expect our model to be a valuable tool in the study of bladder cancer progression due to the exposure to carcinogens and the oxygen dependent expression of genes promoting tumor growth. Our numerical simulations have good qualitative agreement with in vivo results reported in the corresponding medical literature.

  9. Probiotics, dendritic cells and bladder cancer.

    PubMed

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

    2012-06-01

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

  10. Correlation of ANXA1 expression with drug resistance and relapse in bladder cancer

    PubMed Central

    Yu, Shuliang; Meng, Qian; Hu, Huihui; Zhang, Man

    2014-01-01

    Objective: To investigate the expression of annexin a1 (ANXA1) in adriamycin-resistant human bladder cancer cell line (pumc-91/ADM) compared with the parental cell line (pumc-91) and its relevance to the drug resistance of bladder cancer, as well as explore the relevance of ANXA1 in recurrent bladder cancer tissues as pertinent to relapse. Methods: qRT-PCR and Western blot were implemented to research the level of ANXA1 in two cell lines (pumc-91/ADM and pumc-91). Immunohistochemistry was applied to explore ANXA1 expression in bladder cancer tissues of different intervals of relapse. The association of ANXA1 with clinicopathological parameters was analyzed. Results: The expression of ANXA1 was downregulated in drug-resistant cell line pumc-91/ADM compared to pumc-91. The bladder cancer tissues recurring two years later exhibited higher ANXA1 levels. ANXA1 expression level was positively correlated with T stage, while it was not connected with histological grade strongly. The expression level and influencing factors of ANXA1 in recurrent tissues of bladder cancer were clarified for the first time. Conclusion: ANXA1 may become a promising marker to predict the recurrence and drug resistance of bladder cancer and provide guidance for surveillance. PMID:25337195

  11. Safety of three sequential whole bladder photodynamic therapy (WBPDT) treatments in the management of resistant bladder cancer

    NASA Astrophysics Data System (ADS)

    Mejia, Maria C.; Nseyo, Unyime O.

    2009-02-01

    INTRODUCTION: WBPDT has been used to treat resistant superficial bladder cancer, with clinical benefits and associated dose-dependent side effects. OBJECTIVE: The objective of this study was to assess the safety of three sequential WBPDT treatments in patients with resistant non-muscle invasive (NMI) bladder cancer. MATERIALS AND METHODS: 12 males and one female provided written informed consent in this Phase II study. Each patient received intravenous injection of Photofrin® (AXCAN Parma Inc, Canada) at 1.5 mg/kg two days prior to whole bladder laser (630nm) treatment. Assessment of safety and efficacy included weekly urinary symptoms; cystoscopy, biopsy and cytology; and measurement of bladder volume quarterly after each treatment at baseline, six and 12 months. Treatment #2 and/or #3 occurred only in the absence of bladder contracture, and/or disease progression. RESULTS: 13 patients: 12 males and one female have been enrolled and average age of enrollees is 67.1(52 - 87) years. Four patients had Ta-T1/Grade I-III tumors; two patients had CIS associated with T1/GI-III; and seven patients had carcinoma in situ (CIS) only. Three patients received 3/3 treatments, and are evaluable for toxicity; three patients received two treatments only; and seven patients received one treatment only. There was no bladder contracture; transient mild to moderate bladder irritative voiding symptoms of dysuria, urinary frequency, nocturia and urgency occurred in all patients. The three evaluable patients were without evidence of disease at average of 13.1 (7-20) months. CONCLUSION: Three sequential WBPDT treatments might have a favorable toxicity profile in the management of recurrent/ refractory non-muscle invasive bladder cancer.

  12. mTOR inhibitors in urinary bladder cancer.

    PubMed

    Pinto-Leite, R; Arantes-Rodrigues, R; Sousa, Nuno; Oliveira, P A; Santos, L

    2016-09-01

    Despite the great scientific advances that have been made in cancer treatment, there is still much to do, particularly with regard to urinary bladder cancer. Some of the drugs used in urinary bladder cancer treatment have been in use for more than 30 years and show reduced effectiveness and high recurrence rates. There have been several attempts to find new and more effective drugs, to be used alone or in combination with the drugs already in use, in order to overcome this situation.The biologically important mammalian target of rapamycin (mTOR) pathway is altered in cancer and mTOR inhibitors have raised many expectations as potentially important anticancer drugs. In this article, the authors will review the mTOR pathway and present their experiences of the use of some mTOR inhibitors, sirolimus, everolimus and temsirolimus, in isolation and in conjunction with non-mTOR inhibitors cisplatin and gemcitabine, on urinary bladder tumour cell lines. The non-muscle-invasive cell line, 5637, is the only one that exhibits a small alteration in the mTOR and AKT phosphorylation after rapalogs exposure. Also, there was a small inhibition of cell proliferation. With gemcitabine plus everolimus or temsirolimus, the results were encouraging as a more effective response was noticed with both combinations, especially in the 5637 and T24 cell lines. Cisplatin associated with everolimus or temsirolimus also gave promising results, as an antiproliferative effect was observed when the drugs were associated, in particular on the 5637 and HT1376 cell lines. Everolimus or temsirolimus in conjunction with gemcitabine or cisplatin could have an important role to play in urinary bladder cancer treatment, depending on the tumour grading.

  13. Extracellular vesicles as a source for non-invasive biomarkers in bladder cancer progression.

    PubMed

    Andreu, Zoraida; Otta Oshiro, Renan; Redruello, Alberto; López-Martín, Soraya; Gutiérrez-Vázquez, Cristina; Morato, Esperanza; Marina, Ana Isabel; Olivier Gómez, Carlos; Yáñez-Mó, María

    2017-02-15

    Bladder cancer is the second most frequent malignancy of the urinary tract after prostate cancer. Current diagnostic techniques, such as cystoscopy and biopsies are highly invasive and accompanied of undesirable side effects. Moreover, there are no suitable biomarkers for relapse or progression prognosis. We analysed whether the specific composition of microRNAs (miRNAs) and proteins of extracellular vesicles (EVs) that urothelial tumour cells of bladder mucosa release into the urine, could reflect their pathologic condition. For this purpose, urinary EVs were isolated and their protein and miRNA composition evaluated in healthy donors and low or high-grade bladder cancer patients. Using a microarray platform containing probes for 851 human miRNAs we found 26 deregulated miRNAs in high-grade bladder cancer urine EVs, from which 23 were downregulated and 3 upregulated. Real-time PCR analysis pointed to miR-375 as a biomarker for high-grade bladder cancer while miR-146a could identify low-grade patients. Finally, several protein markers were also deregulated in EVs from tumour patients. Our data suggest that the presence of ApoB in the 100,000 pellet is a clear marker for malignancy.

  14. Noninvasive Electromagnetic Detection of Bladder Cancer

    PubMed Central

    Cormio, Luigi; Vedruccio, Clarbruno; Leucci, Giorgio; Massenio, Paolo; Di Fino, Giuseppe; Cavaliere, Vincenzo; Carrieri, Giuseppe

    2014-01-01

    Objectives. Normal and neoplastic human tissues have different electromagnetic properties. This study aimed to determine the diagnostic accuracy of noninvasive electromagnetic detection of bladder cancer (BC) by the tissue-resonance interaction method (TRIM-prob). Patients and Methods. Consecutive patients were referred for cystoscopy because of (i) microscopic or gross hematuria and/or irritative voiding symptoms and (ii) bladder ultrasounds and urinary cytology findings negative or just suspicious of malignancy. Patients were first submitted to TRIM-prob bladder scanning by a single investigator and then to cystoscopy by another investigator blind to TRIM-prob data. Results. In 125 evaluated patients cystoscopy was positive for BC in 47 and negative in the remaining 78; conversely, TRIM-prob bladder scanning was positive for BC in 53 and negative in 72. In particular, TRIM-prob scanning yielded 7 false positives and only one false negative; therefore, its overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 97.9%, 89.9%, 86.8%, 98.6%, and 93.6%, respectively. Conclusions. TRIM-prob bladder scanning was a simple and quite accurate method for non-invasive electromagnetic detection of BC. If the elevated positive and negative predictive values will be replicated in further well-designed studies, it could be used to screen asymptomatic patients at high risk of BC. PMID:24563795

  15. Bladder cancer: approaches to prevention and control*

    PubMed Central

    Koroltchouk, V.; Stanley, K.; Stjernswärd, J.; Mott, K.

    1987-01-01

    Bladder cancer is the twelfth most common cancer globally, with approximately 170 000 new cases each year; a third of these cases are in the developing countries. There are two major etiological types. The first is more common in the industrialized countries and is associated with exposure to certain occupational and environmental carcinogens, but most importantly with tobacco smoking. The second type is associated with Schistosoma haematobium infection of the urinary tract and is one of the most frequent tumours in eastern Mediterranean and African countries. Both types of bladder cancer are largely preventable. Comprehensive education and legislative approaches are recommended to reduce tobacco consumption and exposure to industrial carcinogens. Safe and effective drugs are available to treat schistosomiasis within integrated control programmes in endemic areas. PMID:3121200

  16. Interobserver Agreement of Confocal Laser Endomicroscopy for Bladder Cancer

    PubMed Central

    Chang, Timothy C.; Liu, Jen-Jane; Hsiao, Shelly T.; Pan, Ying; Mach, Kathleen E.; Leppert, John T.; McKenney, Jesse K.; Rouse, Robert V.

    2013-01-01

    Abstract Background and Purpose Emerging optical imaging technologies such as confocal laser endomicroscopy (CLE) hold promise in improving bladder cancer diagnosis. The purpose of this study was to determine the interobserver agreement of image interpretation using CLE for bladder cancer. Methods Experienced CLE urologists (n=2), novice CLE urologists (n=6), pathologists (n=4), and nonclinical researchers (n=5) were recruited to participate in a 2-hour computer-based training consisting of a teaching and validation set of intraoperative white light cystoscopy (WLC) and CLE video sequences from patients undergoing transurethral resection of bladder tumor. Interobserver agreement was determined using the κ statistic. Results Of the 31 bladder regions analyzed, 19 were cancer and 12 were benign. For cancer diagnosis, experienced CLE urologists had substantial agreement for both CLE and WLC+CLE (90%, κ 0.80) compared with moderate agreement for WLC alone (74%, κ 0.46), while novice CLE urologists had moderate agreement for CLE (77%, κ 0.55), WLC (78%, κ 0.54), and WLC+CLE (80%, κ 0.59). Pathologists had substantial agreement for CLE (81%, κ 0.61), and nonclinical researchers had moderate agreement (77%, κ 0.49) in cancer diagnosis. For cancer grading, experienced CLE urologists had fair to moderate agreement for CLE (68%, κ 0.64), WLC (74%, κ 0.67), and WLC+CLE (53%, κ 0.33), as did novice CLE urologists for CLE (53%, κ 0.39), WLC (66%, κ 0.50), and WLC+CLE (61%, κ 0.49). Pathologists (65%, κ 0.55) and nonclinical researchers (61%, κ 0.56) both had moderate agreement for CLE in cancer grading. Conclusions CLE is an adoptable technology for cancer diagnosis in novice CLE observers after a short training with moderate interobserver agreement and diagnostic accuracy similar to WLC alone. Experienced CLE observers may be capable of achieving substantial levels of agreement for cancer diagnosis that is higher than with WLC alone. PMID:23072435

  17. Neoadjuvant Intravesical Vaccine Therapy in Treating Patients With Bladder Carcinoma Who Are Undergoing Cystectomy

    ClinicalTrials.gov

    2014-12-22

    Bladder Adenocarcinoma; Bladder Squamous Cell Carcinoma; Bladder Urothelial Carcinoma; Recurrent Bladder Carcinoma; Stage I Bladder Cancer; Stage II Bladder Cancer; Stage III Bladder Cancer; Stage IV Bladder Cancer

  18. Intravesical Treatments of Bladder Cancer: Review

    PubMed Central

    Shen, Zancong; Shen, Tong; Wientjes, M. Guillaume; O’Donnell, Michael A.

    2008-01-01

    For bladder cancer, intravesical chemo/immunotherapy is widely used as adjuvant therapies after surgical transurethal resection, while systemic therapy is typically reserved for higher stage, muscle-invading, or metastatic diseases. The goal of intravesical therapy is to eradicate existing or residual tumors through direct cytoablation or immunostimulation. The unique properties of the urinary bladder render it a fertile ground for evaluating additional novel experimental approaches to regional therapy, including iontophoresis/electrophoresis, local hyperthermia, co-administration of permeation enhancers, bioadhesive carriers, magnetic-targeted particles and gene therapy. Furthermore, due to its unique anatomical properties, the drug concentration-time profiles in various layers of bladder tissues during and after intravesical therapy can be described by mathematical models comprised of drug disposition and transport kinetic parameters. The drug delivery data, in turn, can be combined with the effective drug exposure to infer treatment efficacy and thereby assists the selection of optimal regimens. To our knowledge, intravesical therapy of bladder cancer represents the first example where computational pharmacological approach was used to design, and successfully predicted the outcome of, a randomized phase III trial (using mitomycin C). This review summarizes the pharmacological principles and the current status of intravesical therapy, and the application of computation to optimize the drug delivery to target sites and the treatment efficacy. PMID:18369709

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

    PubMed Central

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

    2016-01-01

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

  20. Bladder Cancer Screening in Aluminum Smelter Workers

    PubMed Central

    Taiwo, Oyebode A.; Slade, Martin D.; Cantley, Linda F.; Tessier-Sherman, Baylah; Galusha, Deron; Kirsche, Sharon R.; Donoghue, A. Michael

    2015-01-01

    Objective: To present results of a bladder cancer screening program conducted in 18 aluminum smelters in the United States from January 2000 to December 2010. Methods: Data were collected on a cohort of workers with a history of working in coal tar pitch volatile exposed areas including urine analysis for conventional cytology and ImmunoCyt/uCyt+ assay. Results: ImmunoCyt/uCyt+ and cytology in combination showed a sensitivity of 62.30%, a specificity of 92.60%, a negative predictive value of 99.90%, and a positive predictive value of 2.96%. Fourteen cases of bladder cancer were detected, and the standardized incidence ratio of bladder cancer was 1.18 (95% confidence interval, 0.65 to 1.99). Individuals who tested positive on either test who were later determined to be cancer free had undergone expensive and invasive tests. Conclusions: Evidence to support continued surveillance of this cohort has not been demonstrated. PMID:25525927

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

    SciTech Connect

    Turgeon, Guy-Anne; Souhami, Luis; Cury, Fabio L.; Faria, Sergio L.; Duclos, Marie; Sturgeon, Jeremy; Kassouf, Wassim

    2014-02-01

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

  2. Neoadjuvant chemotherapy for invasive bladder cancer.

    PubMed

    Sonpavde, Guru; Sternberg, Cora N

    2012-04-01

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

  3. [Management of bladder cancer in unfit patients].

    PubMed

    Mongiat-Artus, P; Pfister, C; Théodore, C; De Crevoisier, R; Guillotreau, J

    2010-03-01

    Adjuvant therapies in bladder cancer are based on risk of recurrence and associated comorbidities (renal failure). Lymph node involvement is the most important prognostic factor for decision. Two adjuvant chemotherapies exist: MVAC or GC. In unfit patients, association (Gemcitabine and Taxanes) could be proposed. Indication of adjuvant radiotherapy depends on metastatic risk and resection margins. Concomitant chemotherapy and radiotherapy should be proposed to selected patients who refuse or are not candidate for radical cystectomy.

  4. Incidence analyses of bladder cancer in the Nile delta region of Egypt.

    PubMed

    Fedewa, Stacey A; Soliman, Amr S; Ismail, Kadry; Hablas, Ahmed; Seifeldin, Ibrahim A; Ramadan, Mohamed; Omar, Hoda G; Nriagu, Jerome; Wilson, Mark L

    2009-10-01

    Bladder cancer is the most common malignancy among Egyptian males and previously has been attributed to Schistosoma infection, a major risk factor for squamous cell carcinoma (SCC). Recently, transitional cell carcinoma (TCC) incidence has been increasing while SCC has declined. To investigate this shift, we analyzed the geographical patterns of all bladder cancers cases recorded in Egypt's Gharbiah Population-Based Cancer Registry from 1999 through 2002. Data on tumor grade, stage, and morphology, as well as smoking, community of residence, age and sex, were collected on 1209 bladder cancer cases. Age-adjusted incidence rates were calculated for males, females, and the total population for the eight administrative Districts and 316 communities in Gharbiah. Incidence Rate Ratios (IRR) and 95% confidence intervals (CI) were computed using Poisson Regression. The male age-adjusted incidence rate (IR) in Gharbiah Province was 13.65/100,000 person years (PY). The District of Kotour had the highest age-adjusted IR 28.96/100,000 among males. The District of Kotour also had the highest IRR among all Districts, IRR=2.15 95% CI (1.72, 2.70). Kotour's capital city had the highest bladder cancer incidence among the 316 communities (IR=73.11/100,000 PY). Future studies on sources and types of environmental pollution and exposures in relation to the spatial patterns of bladder cancer, particularly in Kotour District, may improve our understating of risk factors for bladder cancer in the region.

  5. Incidence analyses of bladder cancer in the Nile delta region of Egypt

    PubMed Central

    Fedewa, Stacey A.; Soliman, Amr S.; Ismail, Kadry; Hablas, Ahmed; Seifeldin, Ibrahim A.; Ramadan, Mohamed; Omar, Hoda G.; Nriagu, Jerome; Wilson, Mark L.

    2009-01-01

    Bladder cancer is the most common malignancy among Egyptian males and previously has been attributed to Schistosoma infection, a major risk factor for squamous cell carcinoma (SCC). Recently, transitional cell carcinoma (TCC) incidence has been increasing while SCC has declined. To investigate this shift, we analyzed the geographical patterns of all bladder cancers cases recorded in Egypt’s Gharbiah Population-Based Cancer Registry from 1999 through 2002. Data on tumor grade, stage, and morphology, as well as smoking, community of residence, age and sex, were collected on 1,209 bladder cancer cases. Age-adjusted incidence rates were calculated for males, females, and the total population for the eight administrative Districts and 316 communities in Gharbiah. Incidence Rate Ratios (IRR) and 95% Confidence Intervals (CI) were computed using Poisson Regression. The male age-adjusted incidence rate (IR) in Gharbiah Province was 13.65/100,000 person years (PY). The District of Kotour had the highest age-adjusted IR 28.96/100,000 among males. The District of Kotour also had the highest IRR among all Districts, IRR=2.15 95% CI (1.72, 2.70). Kotour’s capital city had the highest bladder cancer incidence among the 316 communities (IR=73.11/100,000 PY). Future studies on sources and types of environmental pollution and exposures in relation to the spatial patterns of bladder cancer, particularly in Kotour District, may improve our understating of risk factors for bladder cancer in the region. PMID:19762298

  6. Urinary bladder cancer in dogs, a naturally occurring model for cancer biology and drug development.

    PubMed

    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.

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

    SciTech Connect

    Kozak, Kevin R.; Hamidi, Maryam; Manning, Matthew; Moody, John S.

    2012-06-01

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

  8. Nursing care and treatment of patients with bladder cancer.

    PubMed

    Turner, B

    Bladder cancer is the second most common urological cancer after prostate cancer in the UK. This article aims to update nurses knowledge about the disease, focusing on diagnosis, treatment and nursing care.

  9. Hair dye use and risk of bladder cancer in the New England bladder cancer study.

    PubMed

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

    2011-12-15

    Aromatic amine components in hair dyes and polymorphisms in genes that encode enzymes responsible for hair dye metabolism may be related to bladder cancer risk. We evaluated the association between hair dye use and bladder cancer risk and effect modification by N-acetyltransferase-1 (NAT1), NAT2, glutathione S-transferase Mu-1 (GSTM1) and glutathione S-transferase theta-1 (GSTT1) genotypes in a population-based case-control study of 1193 incident cases and 1418 controls from Maine, Vermont and New Hampshire enrolled between 2001 and 2004. Individuals were interviewed in person using a computer-assisted personal interview to assess hair dye use and information on potential confounders and effect modifiers. No overall association between age at first use, year of first use, type of product, color, duration or number of applications of hair dyes and bladder cancer among women or men was apparent, but increased risks were observed in certain subgroups. Women who used permanent dyes and had a college degree, a marker of socioeconomic status, had an increased risk of bladder cancer [odds ratio (OR) = 3.3, 95% confidence interval (CI): 1.2-8.9]. Among these women, we found an increased risk of bladder cancer among exclusive users of permanent hair dyes who had NAT2 slow acetylation phenotype (OR = 7.3, 95% CI: 1.6-32.6) compared to never users of dye with NAT2 rapid/intermediate acetylation phenotype. Although we found no relation between hair dye use and bladder cancer risk in women overall, we detected evidence of associations and gene-environment interaction with permanent hair dye use; however, this was limited to educated women. These results need confirmation with larger numbers, requiring pooling data from multiple studies.

  10. Contrast enhanced ultrasound in urothelial carcinoma of urinary bladder: An underutilized staging and grading modality

    PubMed Central

    Gupta, Vijayant Govinda; Singh, Shrawan Kumar; Lal, Anupam; Kakkar, Nandita

    2016-01-01

    Introduction To evaluate contrast enhanced ultrasound (CEUS) as a modality to predict T stage of cancer of urinary bladder (CAUB) and to predict the grade of the tumor preoperatively. Material and methods 110 patients with CAUB presenting to the Department of Urology at our institution between July 2014 and December 2015 underwent CEUS prior to endoscopic resection and the CEUS findings were compared with histopathology results. Results CEUS had a sensitivity of 75, 65 and 90% and specificity of 95, 85 and 92% in detecting Ta, T1 and muscle invasion respectively. CEUS had a sensitivity of 78% and specificity of 85% in detecting the grade of the lesion. Conclusions CEUS is a good alternative for T staging and grading of CAUB preoperatively. It is uniquely advantageous in detecting clots or necrosis and in patients with low eGFR where other imaging modalities are contraindicated. PMID:28127451

  11. The emerging role of the androgen receptor in bladder cancer.

    PubMed

    Lombard, Alan P; Mudryj, Maria

    2015-10-01

    Men are three to four times more likely to get bladder cancer than women. The gender disparity characterizing bladder cancer diagnoses has been investigated. One hypothesis is that androgen receptor (AR) signaling is involved in the etiology and progression of this disease. Although bladder cancer is not typically described as an endocrine-related malignancy, it has become increasingly clear that AR signaling plays a role in bladder tumors. This review summarizes current findings regarding the role of the AR in bladder cancer. We discuss work demonstrating AR expression in bladder cancer and its role in promoting formation and progression of tumors. Additionally, we discuss the therapeutic potential of targeting the AR in this disease.

  12. Human bladder cancer diagnosis using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    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.

  13. Preoperative irradiation and cystectomy for bladder cancer.

    PubMed

    Smith, J A; Batata, M; Grabstald, H; Sogani, P C; Herr, H; Whitmore, W F

    1982-03-01

    Between 1971 and 1974, 101 patients at Memorial Sloan-Kettering Cancer Center underwent planned integrated treatment for bladder cancer with 2000 rads by megavoltage delivered to the whole pelvis over five consecutive days followed by radical cystectomy within a week. The overall five-year survival rate was 39%; the hospital mortality rate was 2%. In the pelvis alone tumor recurred in 9% of the patients. These results support other studies demonstrating the efficacy of this and other regimens of preoperative irradiation and cystectomy.

  14. sEphB4-HSA Before Surgery in Treating Patients With Bladder Cancer, Prostate Cancer, or Kidney Cancer

    ClinicalTrials.gov

    2016-05-06

    Infiltrating Bladder Urothelial Carcinoma; Recurrent Bladder Carcinoma; Stage I Prostate Cancer; Stage I Renal Cell Cancer; Stage II Bladder Urothelial Carcinoma; Stage II Renal Cell Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer

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

    PubMed

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

    2012-07-01

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

  16. Fluorescence detection of bladder cancer: a review.

    PubMed

    D'Hallewin, Marie-Ange; Bezdetnaya, Lina; Guillemin, François

    2002-11-01

    An effective therapeutic outcome in the treatment of bladder cancer is largely defined by its early detection. In this context, big expectations have been placed on the fluorescence-guided diagnosis of bladder cancer. This paper reviews the applications of endo- and exogenous fluorescence for early diagnosis of in situ carcinoma of the bladder. Despite certain advantages of autofluorescence, exogenous fluorescence, based on the intravesical instillation of fluorophores with the following visible light excitation, has been shown to be more effective in terms of sensitivity and specificity for detecting carcinoma in situ. The equipment consists of a slightly modified light source in order to choose between white (conventional endoscopy) or blue light (fluorescence endoscopy) excitation, and specific lenses, in order to enhance maximally the contrast between normal (blue) autofluorescence and red fluorescence from malignancies. Among exogenous fluorophores, a particular emphasis will be put on the 5-aminolevulinic acid (ALA), its ester derivative (h-ALA) and hypericin. These dyes demonstrated an excellent sensitivity above 90% and specificity ranging from 70% to 90%.

  17. Diagnostics techniques in nonmuscle invasive bladder cancer

    PubMed Central

    Soubra, Ayman; Risk, Michael C.

    2015-01-01

    Introduction: Nonmuscle invasive bladder cancer (NMIBC) is the most common presentation of bladder cancer and is often treatable with endoscopic resection and intravesical therapies. Cystoscopy and urine cytology are the gold standard in diagnosis and surveillance but are limited by their sensitivity in some situations. We seek to provide an overview of recent additions to the diagnostic armamentarium for urologists treating this disease. Methods: Articles were identified through a literature review of articles obtained through PubMed searches including the terms “bladder cancer” and various diagnostic techniques described in the article. Results: A variety of urinary biomarkers are available to assist the diagnosis and management of patients with NMIBC. Many have improved sensitivity over urine cytology, but less specificity. There are certain situations in which this has proved valuable, but as yet these are not part of the standard guidelines for NMIBC. Fluorescence cystoscopy has level 1 evidence demonstrating increased rates of tumor detection and prolonged recurrence-free survival when utilized for transurethral resection. Other technologies seeking to enhance cystoscopy, such as narrow band imaging, confocal laser endomicroscopy, and optical coherence tomography are still under evaluation. Conclusions: A variety of urine biomarker and adjunctive endoscopic technologies have been developed to assist the management of NMIBC. While some, such as fluorescence cystoscopy, have demonstrated a definite benefit in this disease, others are still finding their place in the diagnosis and treatment of this disease. Future studies should shed light on how these can be incorporated to improve outcomes in NMIBC. PMID:26604438

  18. Galectin 3 for the diagnosis of bladder cancer

    PubMed Central

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

    2013-01-01

    Objective To evaluate serum levels of galectin-3 (G-3) in patients with bladder cancer and a control group, as a potential diagnostic and prognostic serum tumour marker. Patients and methods Between November 2012 and January 2013, 55 patients (median age 58 years) were enrolled into three groups, i.e., a control, those with transitional cell carcinoma (TCC) or those with squamous cell carcinoma (SCC). The serum G-3 level was measured the night before cystoscopy. The levels of G-3 levels were correlated with tumour type, stage and grade, and in relation to levels in normal urothelium. The results were analysed statistically using the Mann–Whitney U-test, the Kruskal–Wallis test and the receiver operating characteristic curve, as appropriate. Results The median serum G-3 level was 100, 720 and 920 pg/mL in the control, TCC and SCC groups, respectively, with very significantly greater G-3 levels in both the TCC and SCC groups than in the control group. Patients with high-grade TCC had a statistically significantly greater serum G-3 level than those with low-grade tumours, as did those with muscle-invasive TCC than those with Ta tumours. Conclusions The level of G-3 can aid as a diagnostic marker in patients with either TCC or SCC of the bladder, but the prognostic significance of G-3 remains to be confirmed. PMID:26019945

  19. Involvement of cancer-derived IgG in the proliferation, migration and invasion of bladder cancer cells

    PubMed Central

    Sheng, Zhengzuo; Liu, Yang; Qin, Caipeng; Liu, Zhenhua; Yuan, Yeqing; Yin, Huaqi; Qiu, Xiaoyan; Xu, Tao

    2016-01-01

    It is widely accepted that immunoglobulin (Ig), the classical immune molecule, is extensively expressed in many cell types other than B-cells (non-B-IgG), including some malignant cells. The expression of Ig in malignant cells has been associated with a poor prognosis. In the present study, immunohistochemical analysis detected strong positive staining of IgG in three bladder cancer cell lines, the cancer cells in 77 bladder cancer patient samples and the cells in 3 cystitis glandularis tissue samples, while negative staining was observed in 4 specimens of normal transitional epithelial tissues. Importantly, functional transcripts of IgG with unique VHDJH rearrangement patterns were also found in bladder cancer cells. The knockdown of IgG in bladder cancer cell lines using small interfering RNA significantly inhibited the proliferation, migration and invasion of the cells. Notably, high IgG expression, as determined by immunostaining, was significantly correlated with a high histological grade and recurrence. The results of the present study suggested that IgG expression is involved in the malignant biological behavior and poor prognosis of bladder cancer. Therefore, IgG may serve as a novel target for bladder cancer therapy. PMID:28105218

  20. Reprogramming bladder cancer cells for studying cancer initiation and progression.

    PubMed

    Iskender, Banu; Izgi, Kenan; Canatan, Halit

    2016-10-01

    The induced pluripotent stem cell (iPSC) technology is the forced expression of specific transcription factors in somatic cells resulting in transformation into self-renewing, pluripotent cells which possess the ability to differentiate into any type of cells in the human body. While malignant cells could also be reprogrammed into iPSC-like cells with lower efficiency due to the genetic and epigenetic barriers in cancer cells, only a limited number of cancer cell types could be successfully reprogrammed until today. In the present study, we aimed at reprogramming two bladder cancer cell lines HTB-9 and T24 using a non-integrating Sendai virus (SeV) system. We have generated six sub-clones using distinct combinations of four factors-OCT4, SOX2, KLF4 and c-MYC-in two bladder cancer cell lines. Only a single sub-clone, T24 transduced with 4Fs, gave rise to iPSC-like cells. Bladder cancer cell-derived T24 4F cells represent unique features of pluripotent cells such as epithelial-like morphology, colony-forming ability, expression of pluripotency-associated markers and bearing the ability to differentiate in vitro. This is the first study focusing on the reprogramming susceptibility of two different bladder cancer cell lines to nuclear reprogramming. Further molecular characterisation of T24 4F cells could provide a better insight for biomarker research in bladder carcinogenesis and could offer a valuable tool for the development of novel therapeutic approaches in bladder carcinoma.

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

    NASA Astrophysics Data System (ADS)

    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.

  2. Frequent truncating mutations of STAG2 in bladder cancer.

    PubMed

    Solomon, David A; Kim, Jung-Sik; Bondaruk, Jolanta; Shariat, Shahrokh F; Wang, Zeng-Feng; Elkahloun, Abdel G; Ozawa, Tomoko; Gerard, Julia; Zhuang, Dazhong; Zhang, Shizhen; Navai, Neema; Siefker-Radtke, Arlene; Phillips, Joanna J; Robinson, Brian D; Rubin, Mark A; Volkmer, Björn; Hautmann, Richard; Küfer, Rainer; Hogendoorn, Pancras C W; Netto, George; Theodorescu, Dan; James, C David; Czerniak, Bogdan; Miettinen, Markku; Waldman, Todd

    2013-12-01

    Here we report the discovery of truncating mutations of the gene encoding the cohesin subunit STAG2, which regulates sister chromatid cohesion and segregation, in 36% of papillary non-invasive urothelial carcinomas and 16% of invasive urothelial carcinomas of the bladder. Our studies suggest that STAG2 has a role in controlling chromosome number but not the proliferation of bladder cancer cells. These findings identify STAG2 as one of the most commonly mutated genes in bladder cancer.

  3. Frequent truncating mutations of STAG2 in bladder cancer

    PubMed Central

    Solomon, David A.; Kim, Jung-Sik; Bondaruk, Jolanta; Shariat, Shahrokh F.; Wang, Zeng-Feng; Elkahloun, Abdel G.; Ozawa, Tomoko; Gerard, Julia; Zhuang, DaZhong; Zhang, Shizhen; Navai, Neema; Siefker-Radtker, Arleen; Phillips, Joanna J.; Robinson, Brian D.; Rubin, Mark A.; Volkmer, Björn; Hautmann, Richard; Küfer, Rainer; Hogendoorn, Pancras C. W.; Netto, George; Theodorescu, Dan; James, C. David; Czerniak, Bogdan; Miettinen, Markku; Waldman, Todd

    2013-01-01

    Here we report the discovery of truncating mutations of the gene encoding the cohesin subunit STAG2, which regulates sister chromatid cohesion and segregation, in 36% of papillary non-invasive urothelial carcinomas and 16% of invasive urothelial carcinomas of the bladder. Our studies suggest that STAG2 plays a role in controlling chromosome number but not proliferation of bladder cancer cells. These findings identify STAG2 as among the most commonly mutated genes in bladder cancer discovered to date. PMID:24121789

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

    PubMed

    Smith, Sean G; Zaharoff, David A

    2016-01-01

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

  5. Homing peptide guiding optical molecular imaging for the diagnosis of bladder cancer

    NASA Astrophysics Data System (ADS)

    Yang, Xiao-feng; Pang, Jian-zhi; Liu, Jie-hao; Zhao, Yang; Jia, Xing-you; Li, Jun; Liu, Reng-xin; Wang, Wei; Fan, Zhen-wei; Zhang, Zi-qiang; Yan, San-hua; Luo, Jun-qian; Zhang, Xiao-lei

    2014-11-01

    Background: The limitations of primary transurethral resection of bladder tumor (TURBt) have led the residual tumors rates as high as 75%. The intraoperative fluorescence imaging offers a great potential for improving TURBt have been confirmed. So we aim to distinguish the residual tumors and normal mucosa using fluorescence molecular imaging formed by conjugated molecule of the CSNRDARRC bladder cancer homing peptide with fluorescent dye. The conjugated molecule was abbreviated FIuo-ACP. In our study, we will research the image features of FIuo-ACP probe targeted bladder cancer for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo. Methods: After the FIuo-ACP probe was synthetized, the binding sites, factors affecting binding rates, the specificity and the targeting of Fluo-ACP labeled with bladder cancer cells were studied respectively by laser scanning confocal microscope (LSCM), immunofluorescence and multispectral fluorescence ex vivo optical molecular imaging system. Results: The binding sites were located in nucleus and the binding rates were correlated linearly with the dose of probe and the grade of pathology. Moreover, the probe has a binding specificity with bladder cancer in vivo and ex vivo. Tumor cells being labeled by the Fluo-ACP, bright green spots were observed under LSCM. The tissue samples and tumor cells can be labeled and identified by fluorescence microscope. Optical molecular imaging of xenograft tumor tissues was exhibited as fluorescent spots under EMCCD. Conclusion: The CSNRDARRC peptides might be a useful bladder cancer targeting vector. The FIuo-ACP molecular probe was suitable for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo.

  6. Micropapillary Bladder Cancer: Insights from the National Cancer Database

    PubMed Central

    Sui, Wilson; Matulay, Justin T.; James, Maxwell B.; Onyeji, Ifeanyi C.; Theofanides, Marissa C.; RoyChoudhury, Arindam; DeCastro, G. Joel; Wenske, Sven

    2016-01-01

    Introduction: Micropapillary bladder cancer (MPBC) is a variant histology of urothelial carcinoma (UC) that is associated with poor outcomes however given its rarity, little is known outside of institutional reports. We sought to use a population-level cancer database to assess survival outcomes in patients treated with surgery, radiation therapy and/or chemotherapy. Materials and Methods: The National Cancer Database (NCDB) was queried for all cases of MPBC and UC using International Classification of Disease-O-3 morphologic codes between 2004–2014. Primary outcome was survival outcomes stratified by treatment modality. Treatments included radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC). Results: Overall 869 patients with MPBC and 389,603 patients with UC met the inclusion criteria. Median age of the MPBC cohort was 69.9 years (58.9–80.9) with the majority of the cohort presenting with high-grade (89.3%) and muscle invasive or locally advanced disease (47.6%). For cT1 MPBC, outcomes of RC and BPS were not statistically different. For≥cT2 disease, NAC showed a survival benefit compared with RC alone for UC but not for MPBC. On multivariable analysis, MPBC histology independently predicted worse increased risk of death. On subanalysis of the MPBC RC patients, NAC did not improve survival outcomes compared with RC alone. Conclusions: Neoadjuvant chemotherapy utilization and early cystectomy did not show a survival benefit in patients with MPBC. This histology independently predicts decreased survival and prognosis is poor regardless of treatment modality. Further research should focus on developing better treatment options for this rare disease. PMID:28035322

  7. Chemoimmunotherapy of implanted murine bladder cancer.

    PubMed

    Akaza, H; Crabtree, W N; Matheny, R B; Soloway, M S

    1983-03-01

    The unaltered incidence of recurrence of superficial bladder tumor after discontinuation of intravesical chemotherapy has prompted a search for effective adjuvant therapy. The technique of cauterization and implantation of tumor cells was performed in C3H/He mice to simulate the early stage of bladder cancer to evaluate a regimen of intravesical mitomycin C followed by the systemic immunopotentiator, levamisole. Mice received either normal saline (control), mitomycin C (MMC), levamisole (Leva), or MMC plus Leva. Chemotherapy was given intravesically on days 6 and 13. Immunotherapy was given intraperitoneally on days 7 and 14. All mice were sacrificed on day 21. In the treatment groups, the incidences of bladder tumor varied from 50 to 63 per cent whereas that of the control group was 91 per cent. An increase in spleen weight was observed in the treatment groups of Leva and MMC plus Leva as well as the control group but not observed in the group receiving MMC. Our study suggests that although Leva did not reduce the tumor incidence, an immunostimulator might be of benefit when used in conjunction with MMC.

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

    NASA Astrophysics Data System (ADS)

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

    2011-02-01

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

  9. Metabolomics in bladder cancer: a systematic review

    PubMed Central

    Cheng, Yidong; Yang, Xiao; Deng, Xiaheng; Zhang, Xiaolei; Li, Pengchao; Tao, Jun; Qin, Chao; Wei, Jifu; Lu, Qiang

    2015-01-01

    Bladder cancer (BC) is the most common urological malignancy. Early diagnosis of BC is crucial to improve patient outcomes. Currently, metabolomics is a potential technique that can be used to detect BC. We reviewed current publications and synthesised the findings on BC and metabolomics, i.e. metabolite upregulation and downregulation. Fourteen metabolites (lactic acid, leucine, valine, phenylalanine, glutamate, histidine, aspartic acid, tyrosine, serine, uracil, hypoxanthine, carnitine, pyruvic acid and citric acid) were identified as potential biomarkers for BC. In conclusion, this systematic review presents new opportunities for the diagnosis of BC. PMID:26379905

  10. Bladder Cancer Immunotherapy: BCG and Beyond.

    PubMed

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

    2012-01-01

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

  11. Bladder Cancer Immunotherapy: BCG and Beyond

    PubMed Central

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

    2012-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) has become the predominant conservative treatment for nonmuscle invasive bladder cancer. Its mechanism of action continues to be defined but has been shown to involve a T helper type 1 (Th1) immunomodulatory response. While BCG treatment is the current standard of care, a significant proportion of patients fails or do not tolerate treatment. Therefore, many efforts have been made to identify other intravesical and immunomodulating therapeutics to use alone or in conjunction with BCG. This paper reviews the progress of basic science and clinical experience with several immunotherapeutic agents including IFN-α, IL-2, IL-12, and IL-10. PMID:22778725

  12. Quantitative assessment of the relationship between RASSF1A gene promoter methylation and bladder cancer (PRISMA)

    PubMed Central

    Zhan, Leyun; Zhang, Bingyi; Tan, Yaojun; Yang, Chengliang; Huang, Chenhong; Wu, Qiongya; Zhang, Yulin; Chen, Xiaobo; Zhou, Mi; Shu, Aihua

    2017-01-01

    Abstract Background: Methylation of the Ras-association domain family 1 isoform A (RASSF1A) gene promoter region is thought to participate in the initiation and development of many different cancers. However, in bladder cancer the role of RASSF1A methylation was unclear. To evaluate the relationship between RASSF1A methylation and bladder cancer, a quantitative assessment of an independent meta-analysis was performed. In addition, a DNA methylation microarray database from the cancer genome atlas (TCGA) project was used to validate the results of the meta-analysis. Methods: We searched published articles from computerized databases, and DNA methylation data were extracted from TCGA project. All data were analyzed by R software. Results: The results of the meta-analysis indicated that the frequency of RASSF1A gene methylation in bladder cancer patients is significantly higher than in healthy controls. The hazard ratio (HR) was 2.24 (95% CI = [1.45; 3.48], P = 0.0003) for overall survival (OS), and the RASSF1A gene promoter methylation status was strongly associated with the TNM stage and differentiation grade of the tumor. The similar results were also found by the data from TCGA project. Conclusion: There was a significant relationship between the methylation of the RASSF1A gene promoter and bladder cancer. Therefore, RASSF1A gene promoter methylation will be a potential biomarker for the clinical diagnosis of bladder cancer. PMID:28207521

  13. What Are the Risk Factors for Bladder Cancer?

    MedlinePlus

    ... increased risk of urothelial cancers, including bladder cancer. Arsenic in drinking water Arsenic in drinking water has been linked with a ... the world. The chance of being exposed to arsenic depends on where you live and whether you ...

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

    SciTech Connect

    Aluwini, Shafak; Rooij, Peter H.E. van; Kirkels, Wim J.; Boormans, Joost L.; Kolkman-Deurloo, Inger-Karina K.; Wijnmaalen, Arendjan

    2014-03-01

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

  15. Efficient intravesical therapy of bladder cancer with cationic doxorubicin nanoassemblies.

    PubMed

    Jin, Xun; Zhang, Peilan; Luo, Li; Cheng, Hao; Li, Yunzu; Du, Ting; Zou, Bingwen; Gou, Maling

    Nanoparticles have promising applications in drug delivery for cancer therapy. Herein, we prepared cationic 1,2-dioleoyl-3-trimethylammonium propane/methoxypoly (ethyleneglycol) (DPP) nanoparticles to deliver doxorubicin (Dox) for intravesical therapy of bladder cancer. The DPP micelles have a mean dynamic diameter of 18.65 nm and a mean zeta potential of +19.6 mV. The DPP micelles could prolong the residence of Dox in the bladder, enhance the penetration of Dox into the bladder wall, and improve cellular uptake of Dox. The encapsulation by DPP micelles significantly improved the anticancer effect of Dox against orthotopic bladder cancer in vivo. This work described a Dox-loaded DPP nanoparticle with potential applications in intravesical therapy of bladder cancer.

  16. Molecular substratification of bladder cancer: moving towards individualized patient management

    PubMed Central

    Mitra, Anirban P.

    2016-01-01

    Despite advances in surgical techniques, perioperative therapies and postoperative management, outcomes for patients with bladder cancer have largely remained unchanged. Current management of bladder cancer still relies on pathologic staging that does not always reflect the risk for an individual patient. Studies assessing molecular alterations in individual tumors are offering insights into the myriad of cellular pathways that are deregulated in bladder tumorigenesis and progression. Alterations in pathways involved in cell-cycle regulation, apoptosis, cell signaling, angiogenesis and tumor-cell invasion have been shown to influence disease behavior. High-throughput assays are now allowing multiplexed assessment of biomarker alterations, thereby enabling characterization of novel molecular subtypes of bladder cancer. Such approaches have also been used for discovery and validation of robust prognostic molecular signatures. The future of bladder cancer management will rely on the use of validated multimarker panels for risk stratification, optimal surgical management, and theranostic strategies to identify and target specific alterations in individual tumors. PMID:27247631

  17. Efficient intravesical therapy of bladder cancer with cationic doxorubicin nanoassemblies

    PubMed Central

    Jin, Xun; Zhang, Peilan; Luo, Li; Cheng, Hao; Li, Yunzu; Du, Ting; Zou, Bingwen; Gou, Maling

    2016-01-01

    Nanoparticles have promising applications in drug delivery for cancer therapy. Herein, we prepared cationic 1,2-dioleoyl-3-trimethylammonium propane/methoxypoly (ethyleneglycol) (DPP) nanoparticles to deliver doxorubicin (Dox) for intravesical therapy of bladder cancer. The DPP micelles have a mean dynamic diameter of 18.65 nm and a mean zeta potential of +19.6 mV. The DPP micelles could prolong the residence of Dox in the bladder, enhance the penetration of Dox into the bladder wall, and improve cellular uptake of Dox. The encapsulation by DPP micelles significantly improved the anticancer effect of Dox against orthotopic bladder cancer in vivo. This work described a Dox-loaded DPP nanoparticle with potential applications in intravesical therapy of bladder cancer. PMID:27660445

  18. Summary of the 6th Annual Bladder Cancer Think Tank: new directions in urologic research.

    PubMed

    Svatek, Robert S; Rosenberg, Jonathan E; Galsky, Matthew D; Lee, Cheryl T; Latini, David M; Bochner, Bernard H; Weizer, Alon Z; Apolo, Andrea B; Sridhar, Srikala S; Kamat, Ashish M; Hansel, Donna; Flaig, Thomas W; Smith, Norm D; Lotan, Yair

    2013-10-01

    The 6th Annual Bladder Cancer Think Tank brought together a multidisciplinary group of clinicians, researchers, and representatives from the National Cancer Institute and Industry in an effort to advance bladder cancer research efforts. This year's meeting comprised panel discussions and research involving 5 separate working groups, including the Survivorship, Clinical Trials, Standardization of Care, Data Mining, and Translational Science working groups. In this manuscript, the accomplishments and objectives of the working groups are summarized. Notable efforts include: (1) the development of a survivorship care plan for early and late-stage bladder cancer; (2) the development of consensus criteria for eligibility and endpoints for bladder cancer clinical trials; (3) an improved understanding of current practice patterns regarding the use of perioperative chemotherapy in an effort to standardize care; (4) creation of a comprehensive handbook to assist researchers with developing bladder cancer databases; and (5) identification of response to therapy of high-grade non muscle invasive disease through a collaborative exchange of expertise and resources.

  19. Bladder Cancer Treatment | Cancer Trends Progress Report

    Cancer.gov

    The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

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

    PubMed

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

    2016-02-01

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

  1. Comparison of pathological staging and grading of urothelial bladder carcinoma in post-transurethral resection and post-radical cystectomy specimens.

    PubMed

    Poletajew, S; Fus, Ł; Walędziak, M; Pomada, P; Ciechańska, J; Wasiutyński, A; Radziszewski, P; Górnicka, B

    2014-12-01

    Staging and grading of bladder cancer have a substantial impact on patients' prognosis. However, due to the relatively low quality and quantity of specimens from transurethral resection (TUR), initial histopathological examination may not be fully reliable. The aim of this study was to assess the repeatability of staging and grading in post-TUR and post-radical cystectomy (RC) specimens. Staging and grading in TUR and RC specimens were compared in a group of 181 consecutive patients. All microscopic examinations were performed by dedicated uropathologists. Median time from TUR to RC was 45 days. Additionally, an attempt to identify potential clinical variables influencing the risk of discrepancies was made. In post-RC specimens, the disease was down-staged in 13.8% and up-staged in 54.6% of patients (K = -0.03, p < 0.02). Muscle-invasive bladder cancer was diagnosed in 67.6% of patients initially staged as T1. Cancer was down-graded in 10.3% and up-graded in 17.9% of patients (K = 0.44, p < 0.02). Early onset of disease, female sex and time interval from transurethral resection of bladder tumor (TURBT) to RC had no effect on incidence of discrepancies. Pathological post-TUR examination is not predictive for the final stage of cancer. The incidence of under- or overgrading of bladder cancer is significant, and efforts should be made to reduce it.

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

    NASA Astrophysics Data System (ADS)

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

    2012-06-01

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

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

    PubMed

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

    2012-06-21

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

  4. Fibroblast Growth Factor Receptor 3 is a Rational Therapeutic Target in Bladder Cancer

    PubMed Central

    Gust, Kilian M.; McConkey, David J.; Awrey, Shannon; Hegarty, Paul K.; Qing, Jing; Bondaruk, Jolanta; Ashkenazi, Avi; Czerniak, Bogdan; Dinney, Colin P.; Black, Peter C.

    2013-01-01

    Activating mutations of Fibroblast growth factor receptor-3 (FGFR3) have been described in approximately 75% of low-grade papillary bladder tumors. In muscle invasive disease, FGFR3 mutations are found in 20% of tumors, but overexpression of FGFR3 is observed in about half of cases. Therefore, FGFR3 is a particularly promising target for therapy in bladder cancer. Up to now most drugs tested for inhibition of FGFR3 have been small molecule, multi-tyrosine kinase inhibitors. More recently, a specific inhibitory monoclonal antibody targeting FGFR3 (R3Mab) has been described and tested pre-clinically. In this study, we have evaluated mutation and expression status of FGFR3 in 19 urothelial cancer cell lines and a cohort of 170 American bladder cancer patients. We demonstrated inhibitory activity of R3Mab on tumor growth and corresponding cell signaling in three different orthotopic xenografts of bladder cancer. Our results provide the pre-clinical proof of principle necessary to translate FGFR3 inhibition with R3Mab into clinical trials in patients with bladder cancer. PMID:23657946

  5. Fibroblast growth factor receptor 3 is a rational therapeutic target in bladder cancer.

    PubMed

    Gust, Kilian M; McConkey, David J; Awrey, Shannon; Hegarty, Paul K; Qing, Jing; Bondaruk, Jolanta; Ashkenazi, Avi; Czerniak, Bogdan; Dinney, Colin P; Black, Peter C

    2013-07-01

    Activating mutations of fibroblast growth factor receptor-3 (FGFR3) have been described in approximately 75% of low-grade papillary bladder tumors. In muscle-invasive disease, FGFR3 mutations are found in 20% of tumors, but overexpression of FGFR3 is observed in about half of cases. Therefore, FGFR3 is a particularly promising target for therapy in bladder cancer. Up to now, most drugs tested for inhibition of FGFR3 have been small molecule, multityrosine kinase inhibitors. More recently, a specific inhibitory monoclonal antibody targeting FGFR3 (R3Mab) has been described and tested preclinically. In this study, we have evaluated mutation and expression status of FGFR3 in 19 urothelial cancer cell lines and a cohort of 170 American patients with bladder cancer. We have shown inhibitory activity of R3Mab on tumor growth and corresponding cell signaling in three different orthotopic xenografts of bladder cancer. Our results provide the preclinical proof of principle necessary to translate FGFR3 inhibition with R3Mab into clinical trials in patients with bladder cancer.

  6. Targeting protein kinase CK2 suppresses bladder cancer cell survival via the glucose metabolic pathway

    PubMed Central

    Li, Peng; Yuan, Wenbo; Deng, Xiaheng; Cheng, Yidong; Li, Pengchao; Yang, Haiwei; Tao, Jun; Lu, Qiang

    2016-01-01

    Casein kinase 2 (CK2) is a constitutively active serine/threonine kinase that promotes cell proliferation and resists apoptosis. Elevated CK2 expression has been demonstrated in several solid tumors. The expression of CK2α in bladder cancer was elevated in tumor tissues compared with that in adjacent normal tissues. Amplified expression of CK2α was highly correlated with histological grade in bladder cancer(P = 0.024). Knockdown of CK2α in bladder cancer cell lines resulted in a reduction in tumor aerobic glycolysis, accompanied with lower phosphorylated AKT. Moreover, low CK2α levels suppressed cell growth, and similar results could be reproduced after treatment with CX-4945 with a dose-dependent response. CX-4945 inhibited migration and induced apoptosis. Furthermore, knockdown of CK2α decreased the tumorigenicity of bladder cancer cells in vivo. This study is the first to report that CK2 increases glucose metabolism in human bladder cancer. Blocking CK2 function may provide novel diagnostic and potential therapeutic. PMID:27888634

  7. 18F-FDG PET/CT in Bladder Cancer.

    PubMed

    Tagliabue, Luca; Russo, Giovanna; Lucignani, Giovanni

    2016-12-01

    Urinary clearance of F-FDG and variability in bladder wall FDG uptake may hamper the interpretation and limit the use of FDG-PET/CT for imaging bladder tumors. Nevertheless, careful combined evaluation of both CT and FDG-PET images of the urinary tract can provide useful findings. We present 2 cases of bladder cancer detected by FDG-PET/CT. These cases suggest that FDG uptake can be indicative of malignancy in bladder cancer when viewed in conjunction with CT scans and that whole-body FDG-PET/CT scans should always be reviewed with particular attention to the urinary tract because abnormalities suggestive of bladder cancer can be found unexpectedly.

  8. The softening of human bladder cancer cells happens at an early stage of the malignancy process

    PubMed Central

    Ramos, Jorge R; Pabijan, Joanna

    2014-01-01

    Summary Various studies have demonstrated that alterations in the deformability of cancerous cells are strongly linked to the actin cytoskeleton. By using atomic force microscopy (AFM), it is possible to determine such changes in a quantitative way in order to distinguish cancerous from non-malignant cells. In the work presented here, the elastic properties of human bladder cells were determined by means of AFM. The measurements show that non-malignant bladder HCV29 cells are stiffer (higher Young’s modulus) than cancerous cells (HTB-9, HT1376, and T24 cell lines). However, independently of the histological grade of the studied bladder cancer cells, all cancerous cells possess a similar level of the deformability of about a few kilopascals, significantly lower than non-malignant cells. This underlines the diagnostic character of stiffness that can be used as a biomarker of bladder cancer. Similar stiffness levels, observed for cancerous cells, cannot be fully explained by the organization of the actin cytoskeleton since it is different in all malignant cells. Our results underline that it is neither the spatial organization of the actin filaments nor the presence of stress fibers, but the overall density and their 3D-organization in a probing volume play the dominant role in controlling the elastic response of the cancerous cell to an external force. PMID:24778971

  9. Unusual location of a urinary bladder cancer metastasis.

    PubMed

    Forte, Serafino; Kos, Sebastian; Hoffmann, Adrienne

    2009-01-01

    Bladder cancer is the fourth most common malignancy among men in the Western world. Bone metastasis occurs in 27 % of the cases. Usually, the location is the spine. The present report describes the first case of a proven distant bone metastasis to the acromion from a urinary bladder carcinoma in a patient with shoulder pain.

  10. Quantitative measurement of attenuation coefficients of bladder biopsies using optical coherence tomography for grading urothelial carcinoma of the bladder

    NASA Astrophysics Data System (ADS)

    Cauberg, Evelyne C. C.; de Bruin, Daniël M.; Faber, Dirk J.; de Reijke, Theo M.; Visser, Mike; de La Rosette, Jean J. M. C. H.; van Leeuwen, Ton G.

    2010-11-01

    Real-time grading of bladder urothelial carcinoma (UC) is clinically important, but the current standard for grading (histopathology) cannot provide this information. Based on optical coherence tomography (OCT)-measured optical attenuation (μt), the grade of bladder UC could potentially be assessed in real time. We evaluate ex vivo whether μt differs between different grades of UC and benign bladder tissue. Human bladder tissue specimens are examined ex vivo by 850-nm OCT using dynamic focusing. Three observers independently determine the μt from the OCT images, and three pathologists independently review the corresponding histology slides. For both methods, a consensus diagnosis is made. We include 76 OCT scans from 54 bladder samples obtained in 20 procedures on 18 patients. The median (interquartile range) μt of benign tissue is 5.75 mm-1 (4.77 to 6.14) versus 5.52 mm-1 (3.47 to 5.90), 4.85 mm-1 (4.25 to 6.50), and 5.62 mm-1 (5.01 to 6.29) for grade 1, 2, and 3 UC, respectively (p = 0.732). Interobserver agreement of histopathology is ``substantial'' [Kappa 0.62, 95% confidence interval (IC) 0.54 to 0.70] compared to ``almost perfect'' [interclass correlation coefficient (ICC) 0.87, 95% CI 0.80 to 0.92] for OCT. Quantitative OCT analysis (by μt) does not detect morphological UC changes. This may be due to factors typical for an ex-vivo experimental setting.

  11. Quantitative diagnosis of bladder cancer by morphometric analysis of HE images

    NASA Astrophysics Data System (ADS)

    Wu, Binlin; Nebylitsa, Samantha V.; Mukherjee, Sushmita; Jain, Manu

    2015-02-01

    In clinical practice, histopathological analysis of biopsied tissue is the main method for bladder cancer diagnosis and prognosis. The diagnosis is performed by a pathologist based on the morphological features in the image of a hematoxylin and eosin (HE) stained tissue sample. This manuscript proposes algorithms to perform morphometric analysis on the HE images, quantify the features in the images, and discriminate bladder cancers with different grades, i.e. high grade and low grade. The nuclei are separated from the background and other types of cells such as red blood cells (RBCs) and immune cells using manual outlining, color deconvolution and image segmentation. A mask of nuclei is generated for each image for quantitative morphometric analysis. The features of the nuclei in the mask image including size, shape, orientation, and their spatial distributions are measured. To quantify local clustering and alignment of nuclei, we propose a 1-nearest-neighbor (1-NN) algorithm which measures nearest neighbor distance and nearest neighbor parallelism. The global distributions of the features are measured using statistics of the proposed parameters. A linear support vector machine (SVM) algorithm is used to classify the high grade and low grade bladder cancers. The results show using a particular group of nuclei such as large ones, and combining multiple parameters can achieve better discrimination. This study shows the proposed approach can potentially help expedite pathological diagnosis by triaging potentially suspicious biopsies.

  12. AB111. Genetic variations rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population

    PubMed Central

    Zhang, Yu; Hu, Hailong; Tian, Dawei; Wu, Changli

    2016-01-01

    Objective Genome-wide association studies (GWAS) have identified a number of genetic variants associated with risk of bladder cancer in populations of European descent. Methods we assessed association of two of these variants, rs11892031 (2q37.1 region) and rs401681 (5p15.33 region) in a Chinese case-control study, which included 367 bladder cancer cases and 420 controls. Results We found that the AC genotype of rs11892031 was associated with remarkably decreased risk of bladder cancer [adjusted odds ratio (OR), 0.27; 95% confidence interval (CI), 0.09–0.81; P=0.019), compared with the AA genotype of rs11892031; and that CT/CC genotypes of rs401681 were associated with significantly increased risk of bladder cancer (adjusted OR, 1.79; 95% CI, 1.10–2.91; P=0.02), compared with the TT genotype of rs401681. We further conducted stratification analysis to examine the correlation between single nucleotide polymorphism (SNP) rs11892031/rs401681 and tumor grade/stage. Results showed that heterogeneity in ORs of tumor categories was not significant for either rs11892031 or rs401681 (P>0.05), indicating that the two SNPs seemingly do not associate with tumor grade and stage of bladder cancer in our study population. Conclusions The present study suggests that the SNPs rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population.

  13. Genetic variant as a marker for bladder cancer therapy

    Cancer.gov

    Patients who have inherited a specific common genetic variant develop bladder cancer tumors that strongly express a protein known as prostate stem cell antigen (PSCA), which is also expressed in many pancreatic and prostate tumors, according to research a

  14. TCGA Bladder Cancer Study Reveals Potential Drug Targets - TCGA

    Cancer.gov

    Investigators with the TCGA Research Network have identified new potential therapeutic targets for a major form of bladder cancer, including important genes and pathways that are disrupted in the disease.

  15. TCGA bladder cancer study reveals potential drug targets

    Cancer.gov

    Investigators with TCGA have identified new potential therapeutic targets for a major form of bladder cancer, including important genes and pathways that are disrupted in the disease. They also discovered that, at the molecular level, some subtypes of bla

  16. Genomic Landscape of Experimental Bladder Cancer in Rodents and Its Application to Human Bladder Cancer: Gene Amplification and Potential Overexpression of Cyp2a5/CYP2A6 Are Associated with the Invasive Phenotype

    PubMed Central

    Kanemoto, Kazuhiro; Fukuta, Katsuhiro; Kawai, Noriyasu; Tozawa, Keiichi; Ochiai, Masako; Okamoto, Koji; Ohnami, Sumiko; Sakamoto, Hiromi; Yoshida, Teruhiko; Kanai, Yae; Katoh, Masaru; Yasui, Takahiro; Kohri, Kenjiro; Kakizoe, Tadao; Nakagama, Hitoshi

    2016-01-01

    Non-muscle invasive (superficial) bladder cancer is a low-grade malignancy with good prognosis, while muscle invasive (invasive) bladder cancer is a high-grade malignancy with poor prognosis. N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) induces superficial bladder cancers with papillary morphology in rats and invasive bladder cancers with infiltrating phenotype in mice. In this study, we analyzed genomic landscapes of rodent BBN-induced bladder cancers using array-based comparative genomic hybridization (array CGH). While no significant copy number alterations were detected in superficial bladder tumors in rats, copy number gains in chromosomal regions 2D-E1, 7qA3, 9F2, and 11C-D were detected in invasive bladder tumors in mice. Amplification of representative genes located on 2D-E1 and 7qA3 chromosomal regions was confirmed by quantitative PCR. Cyp2a22 and Cyp2a5 genes but not Cyp2g1, Cyp2a12, and Rab4b genes on mouse chromosome 7qA3 were amplified in invasive bladder cancers. Although the human ortholog gene of Cyp2a22 has not been confirmed, the mouse Cyp2a5 gene is the ortholog of the human CYP2A6 gene located in chromosomal region 19q13.2, and CYP2A6 was identified by database search as one of the closest human homolog to mouse Cyp2a22. Considering a possibility that this region may be related to mouse 7qA3, we analyzed CYP2A6 copy number and expression in human bladder cancer using cell lines and resected tumor specimens. Although only one of eight cell lines showed more than one copy increase of the CYP2A6 gene, CYP2A6 amplification was detected in six out of 18 primary bladder tumors where it was associated with the invasive phenotype. Immunohistochemical analyses of 118 primary bladder tumors revealed that CYP2A6 protein expression was also higher in invasive tumors, especially in those of the scattered type. Together, these findings indicate that the amplification and overexpression of the CYP2A6 gene are characteristic of human bladder cancers with

  17. Involvement of the Androgen and Glucocorticoid Receptors in Bladder Cancer

    PubMed Central

    McBeth, Lucien; Grabnar, Maria; Selman, Steven; Hinds, Terry D.

    2015-01-01

    Bladder cancer is encountered worldwide having been associated with a host of environmental and lifestyle risk factors. The disease has a male to female prevalence of 3 : 1. This disparity has raised the possibility of the androgen receptor (AR) pathway being involved in the genesis of the disease; indeed, research has shown that AR is involved in and is likely a driver of bladder cancer. Similarly, an inflammatory response has been implicated as a major player in bladder carcinogenesis. Consistent with this concept, recent work on anti-inflammatory glucocorticoid signaling points to a pathway that may impact bladder cancer. The glucocorticoid receptor- (GR-) α isoform has an important role in suppressing inflammatory processes, which may be attenuated by AR in the development of bladder cancer. In addition, a GR isoform that is inhibitory to GRα, GRβ, is proinflammatory and has been shown to induce cancer growth. In this paper, we review the evidence of inflammatory mediators and the relationship of AR and GR isoforms as they relate to the propensity for bladder cancer. PMID:26347776

  18. Combination of Rapamycin and Resveratrol for Treatment of Bladder Cancer.

    PubMed

    Alayev, Anya; Salamon, Rachel S; Schwartz, Naomi S; Berman, Adi Y; Wiener, Sara L; Holz, Marina K

    2017-02-01

    Loss of TSC1 function, a crucial negative regulator of mTOR signaling, is a common alteration in bladder cancer. Mutations in other members of the PI3K pathway, leading to mTOR activation, are also found in bladder cancer. This provides rationale for targeting mTOR for treatment of bladder cancer characterized by TSC1 mutations and/or mTOR activation. In this study, we asked whether combination treatment with rapamycin and resveratrol could be effective in concurrently inhibiting mTOR and PI3K signaling and inducing cell death in bladder cancer cells. In combination with rapamycin, resveratrol was able to block rapamycin-induced Akt activation, while maintaining mTOR pathway inhibition. In addition, combination treatment with rapamycin and resveratrol induced cell death specifically in TSC1(-/-) MEF cells, and not in wild-type MEFs. Similarly, resveratrol alone or in combination with rapamycin induced cell death in human bladder cancer cell lines. These data indicate that administration of resveratrol together with rapamycin may be a promising therapeutic option for treatment of bladder cancer. J. Cell. Physiol. 232: 436-446, 2017. © 2016 Wiley Periodicals, Inc.

  19. Bladder and rectal complications following radiotherapy for cervix cancer

    SciTech Connect

    Stryker, J.A.; Bartholomew, M.; Velkley, D.E.; Cunningham, D.E.; Mortel, R.; Craycraft, G.; Shafer, J.

    1988-01-01

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

  20. Novel non invasive diagnostic strategies in bladder cancer

    PubMed Central

    TRUTA, ANAMARIA; POPON, TUDOR ADRIAN HODOR; SARACI, GEORGE; GHERVAN, LIVIU; POP, IOAN VICTOR

    2016-01-01

    Bladder cancer is one of the most commonly diagnosed malignancies worldwide, derived from the urothelium of the urinary bladder and defined by long asymptomatic and atypical clinical picture. Its complex etiopathogenesis is dependent on numerous risk factors that can be divided into three distinct categories: genetic and molecular abnormalities, chemical or environmental exposure and previous genitourinary disorders and family history of different malignancies. Various genetic polymorphisms and microRNA might represent useful diagnostic or prognostic biomarkers. Genetic and molecular abnormalities - risk factors are represented by miRNA or genetic polymorphisms proved to be part of bladder carcinogenesis such as: genetic mutations of oncogenes TP53, Ras, Rb1 or p21 oncoproteins, cyclin D or genetic polymorhisms of XPD,ERCC1, CYP1B1, NQO1C609T, MDM2SNP309, CHEK2, ERCC6, NRF2, NQO1Pro187Ser polymorphism and microRNA (miR-143, −145, −222, −210, −10b, 576-3p). The aim of our article is to highlight the most recent acquisitions via molecular biomarkers (miRNAs and genetic polymorphisms) involved in bladder cancer in order to provide early diagnosis, precise therapy according to the molecular profile of bladder tumors, as well as to improve clinical outcome, survival rates and life quality of oncological patients. These molecular biomarkers play a key role in bladder carcinogenesis, clinical evolution, prognosis and therapeutic response and explain the molecular mechanisms involved in bladder carcinogenesis; they can also be selected as therapeutic targets in developing novel therapeutic strategies in bladder malignancies. Moreover, the purpose in defining these molecular non invasive biomarkers is also to develop non invasive screening programs in bladder malignancies with the result of decreasing bladder cancer incidence in risk population. PMID:27152066

  1. Novel non invasive diagnostic strategies in bladder cancer.

    PubMed

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

    2016-01-01

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

  2. Immune Response Following Photodynamic Therapy For Bladder Cancer

    NASA Astrophysics Data System (ADS)

    Raymond K.

    1989-06-01

    This study was undertaken to determine if photodynamic therapy (PDT) produces an immunologic response in patients treated for bladder cancer. Gamma interferon, interleukin 1-beta, interleukin 2 and tumor necrosis factor-alpha were assayed in the urine of four patients treated with photodynamic therapy for bladder cancer, in seven patients undergoing transurethral procedures, and in five healthy control subjects. Quantifiable concentrations of all cytokines, except gamma interferon, were measured in urine samples from the PDT patients treated with the highest light energies, while no urinary cytokines were found in the PDT patient who received the lowest light energy or in the control subjects. These findings suggest that a local immunologic response may occur following PDT for bladder cancer. Such an immunologic response activated by PDT may be an additional mechanism involved in bladder tumor destruction.

  3. Lymphatic vessel density and function in experimental bladder cancer

    PubMed Central

    Saban, Marcia R; Towner, Rheal; Smith, Nataliya; Abbott, Andrew; Neeman, Michal; Davis, Carole A; Simpson, Cindy; Maier, Julie; Mémet, Sylvie; Wu, Xue-Ru; Saban, Ricardo

    2007-01-01

    Background The lymphatics form a second circulatory system that drains the extracellular fluid and proteins from the tumor microenvironment, and provides an exclusive environment in which immune cells interact and respond to foreign antigen. Both cancer and inflammation are known to induce lymphangiogenesis. However, little is known about bladder lymphatic vessels and their involvement in cancer formation and progression. Methods A double transgenic mouse model was generated by crossing a bladder cancer-induced transgenic, in which SV40 large T antigen was under the control of uroplakin II promoter, with another transgenic mouse harboring a lacZ reporter gene under the control of an NF-κB-responsive promoter (κB-lacZ) exhibiting constitutive activity of β-galactosidase in lymphatic endothelial cells. In this new mouse model (SV40-lacZ), we examined the lymphatic vessel density (LVD) and function (LVF) during bladder cancer progression. LVD was performed in bladder whole mounts and cross-sections by fluorescent immunohistochemistry (IHC) using LYVE-1 antibody. LVF was assessed by real-time in vivo imaging techniques using a contrast agent (biotin-BSA-Gd-DTPA-Cy5.5; Gd-Cy5.5) suitable for both magnetic resonance imaging (MRI) and near infrared fluorescence (NIRF). In addition, IHC of Cy5.5 was used for time-course analysis of co-localization of Gd-Cy5.5 with LYVE-1-positive lymphatics and CD31-positive blood vessels. Results SV40-lacZ mice develop bladder cancer and permitted visualization of lymphatics. A significant increase in LVD was found concomitantly with bladder cancer progression. Double labeling of the bladder cross-sections with LYVE-1 and Ki-67 antibodies indicated cancer-induced lymphangiogenesis. MRI detected mouse bladder cancer, as early as 4 months, and permitted to follow tumor sizes during cancer progression. Using Gd-Cy5.5 as a contrast agent for MRI-guided lymphangiography, we determined a possible reduction of lymphatic flow within the

  4. Complementary and alternative medicine (CAM) in prostate and bladder cancer.

    PubMed

    Philippou, Yiannis; Hadjipavlou, Marios; Khan, Shahid; Rane, Abhay

    2013-12-01

    To provide an overview of the scientific and clinical studies underlying the most common vitamin and herbal preparations used in prostate and bladder cancer and evaluate the evidence behind them. A literature search was undertaken on PubMed using various keywords relating to the use of complementary and alternative medicine (CAM) in prostate and bladder cancer.Vitamin E and selenium supplementation can potentially have adverse effects by increasing the risk of prostate cancer. Initial clinical studies of pomegranate and green tea, investigating their chemotherapeutic properties in prostate and bladder cancer have yielded encouraging results. Curcumin, resveratrol, and silibinin have potential anticancer properties through multiple molecular targets; their clinical effectiveness in prostate and bladder cancer is yet to be evaluated. Zyflamend, like PC-SPES, is a combined CAM therapy used in prostate cancer. Acupuncture is popular among patients experiencing hot flushes who are receiving androgen-deprivation therapy for prostate cancer. Conclusive evidence for the use of CAM in prostate and bladder cancer is lacking and not without risk.

  5. High Expression of Derlin-1 Is Associated with the Malignancy of Bladder Cancer in a Chinese Han Population

    PubMed Central

    Zhang, Zhan; Liu, Wenlou; Xu, Hengsen; Wang, Huanqiang; Wang, Yun; Zhang, Wei; Wang, Shou-Lin

    2016-01-01

    Derlin-1 is overexpressed in various types of solid tumors and has an important function in cancer progression. However, its expression pattern in and association with the clinicopathological characteristics of human bladder cancer remain unclear. In the present study, 3 pairs of fresh samples of bladder cancer tissue and paracancerous tissue were first detected by liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to screen for differentially expressed proteins. Following bioinformatics analysis and assessments by qRT-PCR and western blotting, Derlin-1 was selected as a candidate protein and was then validated in samples from patients with bladder cancer by immunohistochemistry and western blotting. The results showed that the bladder cancer tissues exhibited higher levels of Derlin-1 expression than the paracancerous tissues (P < 0.05). Positive expression of Derlin-1 was significantly correlated with tumor stage, histological grade, and lymph node metastasis (P < 0.001) but was not correlated with other clinicopathological parameters including patient age (P = 0.758) and gender (P = 0.831). Besides, Derlin-1 was highly expressed in BC cell lines (um-uc-3 and T24), and the interference of Derlin-1 could reverse EMT progression, inhibit the tumor migration and invasion in T24 cells. Further, patients with positive Derlin-1 expression had shorter overall survival than those with negative expression (P < 0.001). Taken together, our results demonstrated that Derlin-1 was overexpressed in bladder cancer and was associated with the malignancy of bladder cancer. PMID:27977784

  6. Searching for urine biomarkers of bladder cancer recurrence using a liquid chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry metabolomics approach.

    PubMed

    Alberice, Juliana Vieira; Amaral, Andre F S; Armitage, Emily Grace; Lorente, José Antonio; Algaba, Ferrán; Carrilho, Emanuel; Márquez, Mirari; García, Antonia; Malats, Núria; Barbas, Coral

    2013-11-29

    The incidence and rate of recurrence of bladder cancer is high, particularly in developed countries, however current methods for diagnosis are limited to detecting high-grade tumours using often invasive methods. A panel of biomarkers to characterise tumours of different grades that could also distinguish between patients exhibiting the disease with first incidence or recurrence could be useful for bladder cancer diagnostics. In this study, potential metabolic biomarkers have been discovered through mass spectrometry based metabolomics of urine. Pre-treatment urine samples were collected from 48 patients diagnosed of urothelial bladder cancer. Patients were followed-up through the hospital pathological charts to identify whether and when the disease recurred or progressed. Subsequently, they were classified according to whether or not they suffered a tumour recurrence (recurrent or stable) as well as their risk group according to tumour grade and stage. Identified metabolites have been analysed in terms of disease characteristics (tumour stage and recurrence) and have provided an insight into bladder cancer progression. Using both liquid chromatography and capillary electrophoresis-mass spectrometry, a total of 27 metabolite features were highlighted as significantly different between patient groups. Some, for example histidine, phenylalanine, tyrosine and tryptophan have been previously linked with bladder cancer, however until now their connection with bladder cancer progression has not been previously reported. The candidate biomarkers revealed in this study could be useful in the clinic for diagnosis of bladder cancer and, through characterising the stage of the disease, could also be useful in prognostics.

  7. Occupational risk of bladder cancer among Iranian male workers

    PubMed Central

    Aminian, Omid; Saburi, Amin; Mohseni, Hossein; Akbari, Hamed; Chavoshi, Farzaneh; Akbari, Hesam

    2014-01-01

    Background: Approximately 5-10% of human cancers are thought to be caused by occupational exposure to carcinogens. Compare to other cancers, bladder cancer is most strongly linked to occupational exposure to chemical toxins. This study has been performed to understand which occupations and exposures are related to bladder cancer in Iran. Materials and Methods: This study is a case-control study which is conducted on cases with bladder cancer (160 cases) diagnosed in Baharlou hospital in 2007-2009. One hundred sixty cases without any occupational exposure were considered as controls matched for demographic characteristics. Demographic data and characteristics of occupation were compared. Results: Mean age of cases and controls were 63.7 and 64 years, respectively (P = 0.841). History of urinary tract stone had significantly difference in two groups (P = 0.039). Occupations such as bus and truck driving, road and asphalt making, mechanics, working in refinery and Petrochemical, plastic, metal manufactory, welding, and pipeline founded a higher risk for bladder cancer rather than controls. Conclusion: Our findings on Iranian workers are concurrent and compatible with findings of previous reports about occupational and environmental risk factors of bladder cancer. Although our study population was PMID:24833825

  8. DAPK Promoter Methylation and Bladder Cancer Risk: A Systematic Review and Meta-Analysis

    PubMed Central

    Zhang, Zhensheng; Zeng, Shuxiong; Liu, Anwei; Tang, Shijie; Ren, Qian; Sun, Yinghao; Xu, Chuanliang

    2016-01-01

    Background Methylation of tumor suppressor gene promoter leads to transcription inactivation and is involved in tumorigenesis. Several studies demonstrate a potential association between the Death-Associated Protein Kinase (DAPK) gene promoter methylation and bladder cancer risk, tumor stage and histological grade. Due to inconsistent results of these studies, we performed this meta-analysis to ascertain the association. Methods Studies were retrieved from the PubMed, Embase, Web of Science and the Cochrane Library databases. Study selection and data extraction were executed by two reviewers independently. Meta-analysis was performed using Stata 13.0 and Review Manager 5.3 software. Results A total of 21 articles involving 15 case control and 8 case series studies were included in this meta-analysis. DAPK promoter methylation was associated with bladder cancer risk (OR: 5.81; 95%CI = 3.83–8.82, P<0.00001). The frequency of DAPK promoter methylation was equal in bladder cancer tissue and paired adjacent normal tissue (OR: 0.87; 95%CI = 0.31–2.48, P = 0.794). Furthermore, DAPK promoter methylation was associated with higher histological grade (OR: 1.52; 95%CI = 1.10–2.09, P = 0.011) but not associated with tumor stage (OR: 1.12; 95%CI = 0.67–1.87, P = 0.668). Conclusions The result suggests that DAPK promoter methylation is significantly increased in bladder cancer patients compared to normal controls. DAPK promoter methylation could serve as a biomarker for bladder cancer detection and management. PMID:27907054

  9. Key concerns about the current state of bladder cancer: a position paper from the Bladder Cancer Think Tank, the Bladder Cancer Advocacy Network, and the Society of Urologic Oncology.

    PubMed

    Lotan, Yair; Kamat, Ashish M; Porter, Michael P; Robinson, Victoria L; Shore, Neal; Jewett, Michael; Schelhammer, Paul F; deVere White, Ralph; Quale, Diane; Lee, Cheryl T

    2009-09-15

    Bladder cancer is the fifth most common cancer in the United States and, on a per capita basis, is the most expensive cancer from diagnosis to death. Unfortunately, National Cancer Institute funding for bladder cancer is quite low when compared with other common malignancies. Limited funding has stifled research opportunities for new and established investigators, ultimately encouraging them to redirect research efforts to other organ sites. Waning interest of scientists has further fueled the cycle of modest funding for bladder cancer. One important consequence of this has been a lack of scientific advancement in the field. Patient advocates have decidedly advanced research efforts in many cancer sites. Breast, prostate, pancreatic, and ovarian cancer advocates have organized highly successful campaigns to lobby the federal government and the medical community to devote increased attention and funding to understudied malignancies and to conduct relevant studies to better understand the therapy, diagnosis, and prevention of these diseases. Bladder cancer survivors have lacked a coordinated advocacy voice until recently. A concerted effort to align bladder cancer advocates, clinicians, and urologic organizations is essential to define the greatest needs in bladder cancer and to develop related solutions. This position paper represents a collaborative discussion to define the most concerning trends and greatest needs in the field of bladder cancer as outlined by the Bladder Cancer Think Tank, the Bladder Cancer Advocacy Network, and the Society of Urologic Oncology.

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

    SciTech Connect

    Stam, Marcel R. . E-mail: m.stam@rther.umcn.nl; Lin, Emile N.J. Th. van; Vight, Lisette P. van der; Kaanders, Johannes; Visser, Andries G.

    2006-06-01

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

  11. Ciprofloxacin criteria in antimicrobial prophylaxis and bladder cancer recurrence.

    PubMed

    Gurtowska, Natalia; Kloskowski, Tomasz; Drewa, Tomasz

    2010-10-01

    Oral ciprofloxacin might achieve higher concentration in urine than in serum; theoretically, this drug might act as an anticancer drug against bladder cancer cells. Among fluoroquinolones, ciprofloxacin is distinguished by strong inhibition of topoisomerase II. A good correlation between cytotoxic activity of ciprofloxacin toward eukaryotic cells and its ability to induce the cleavable complexes topoisomerase II-DNA has been demonstrated. These data provide a basis for supposing that ciprofloxacin may act as anticancer drug. The efforts of evaluating ciprofloxacin's influence on human bladder cell lines have been shown by many authors. The cells were exposed to ciprofloxacin at various concentrations that are attainable in the urine after oral drug administration. Antiproliferative potential of the ciprofloxacin against human bladder cells varies according to drug concentration and time of incubation. It seems that ciprofloxacin can act as an anticancer drug in eukaryotic cells. Low urine pH can enhance the antitumor effect of ciprofloxacin. Ciprofloxacin enhances the effect of action of doxorubicin and epirubicin, which are used to prevent bladder cancer recurrence after transurethral resection of superficial bladder cancer. We think that ciprofloxacin might be used for antibacterial prophylaxis and as an anticancer agent in patients with superficial bladder cancer. This idea must be checked in future placebo controlled trials.

  12. HPLC assisted Raman spectroscopic studies on bladder cancer

    NASA Astrophysics Data System (ADS)

    Zha, W. L.; Cheng, Y.; Yu, W.; Zhang, X. B.; Shen, A. G.; Hu, J. M.

    2015-04-01

    We applied confocal Raman spectroscopy to investigate 12 normal bladder tissues and 30 tumor tissues, and then depicted the spectral differences between the normal and the tumor tissues and the potential canceration mechanism with the aid of the high-performance liquid chromatographic (HPLC) technique. Normal tissues were demonstrated to contain higher tryptophan, cholesterol and lipid content, while bladder tumor tissues were rich in nucleic acids, collagen and carotenoids. In particular, β-carotene, one of the major types of carotenoids, was found through HPLC analysis of the extract of bladder tissues. The statistical software SPSS was applied to classify the spectra of the two types of tissues according to their differences. The sensitivity and specificity of 96.7 and 66.7% were obtained, respectively. In addition, different layers of the bladder wall including mucosa (lumps), muscle and adipose bladder tissue were analyzed by Raman mapping technique in response to previous Raman studies of bladder tissues. All of these will play an important role as a directive tool for the future diagnosis of bladder cancer in vivo.

  13. Insight into the molecular basis of Schistosoma haematobium-induced bladder cancer through urine proteomics.

    PubMed

    Bernardo, Carina; Cunha, Maria Cláudia; Santos, Júlio Henrique; da Costa, José M Correia; Brindley, Paul J; Lopes, Carlos; Amado, Francisco; Ferreira, Rita; Vitorino, Rui; Santos, Lúcio Lara

    2016-08-01

    Infection due to Schistosoma haematobium is carcinogenic. However, the cellular and molecular mechanisms underlying urogenital schistosomiasis (UGS)-induced carcinogenesis have not been well defined. Conceptually, early molecular detection of this phenomenon, through non-invasive procedures, seems feasible and is desirable. Previous analysis of urine collected during UGS suggests that estrogen metabolites, including depurinating adducts, may be useful for this purpose. Here, a new direction was pursued: the identification of molecular pathways and potential biomarkers in S. haematobium-induced bladder cancer by analyzing the proteome profiling of urine samples from UGS patients. GeLC-MS/MS followed by protein-protein interaction analysis indicated oxidative stress and immune defense systems responsible for microbicide activity are the most representative clusters in UGS patients. Proteins involved in immunity, negative regulation of endopeptidase activity, and inflammation were more prevalent in UGS patients with bladder cancer, whereas proteins with roles in renal system process, sensory perception, and gas and oxygen transport were more abundant in subjects with urothelial carcinoma not associated with UGS. These findings highlighted a Th2-type immune response induced by S. haematobium, which seems to be further modulated by tumorigenesis, resulting in high-grade bladder cancer characterized by an inflammatory response and complement activation alternative pathway. These findings established a starting point for the development of multimarker strategies for the early detection of UGS-induced bladder cancer.

  14. PET/Computed Tomography in Renal, Bladder, and Testicular Cancer.

    PubMed

    Bouchelouche, Kirsten; Choyke, Peter L

    2015-07-01

    Imaging plays an important role in the clinical management of cancer patients. Hybrid imaging with PET/computed tomography (CT) is having a broad impact in oncology, and in recent years PET/CT is beginning to have an impact in urooncology. In both bladder and renal cancers, there is a need to study the efficacy of other tracers than F-18 fluorodeoxyglucose (FDG), particularly tracers with limited renal excretion. Thus, new tracers are being introduced. This review focuses on the clinical role of FDG and other PET agents in renal, bladder, and testicular cancers.

  15. PET/CT in renal, bladder and testicular cancer

    PubMed Central

    Bouchelouche, Kirsten; Physician, Chief; Choyke, Peter L.

    2015-01-01

    Imaging plays an important role in the clinical management of cancer patients. Hybrid imaging with PET/CT is having a broad impact in oncology, and in recent years PET/CT is beginning to have an impact in uro-oncology as well. In both bladder and renal cancer there is a need to study the efficacy of other tracers than F-18 fluorodeoxyglucose (FDG), particularly tracers with only limited renal excretion. Thus, new tracers are being introduced in these malignancies. This review focuses on the clinical role of FDG and other PET agents in renal, bladder and testicular cancer. PMID:26099672

  16. Urinary APE1/Ref-1: A Potential Bladder Cancer Biomarker.

    PubMed

    Choi, Sunga; Shin, Ju Hyun; Lee, Yu Ran; Joo, Hee Kyoung; Song, Ki Hak; Na, Yong Gil; Chang, Seok Jong; Lim, Jae Sung; Jeon, Byeong Hwa

    2016-01-01

    Bladder cancer (BCa) is one of the most common urothelial cancers with still noticeable incidence rate. Early detection of BCa is highly correlated with successful therapeutic outcomes. We previously showed that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) was expressed at an increased level in the serum of BCa patients when compared to the level in healthy controls. In this study, we investigated whether urinary APE1/Ref-1 was also elevated in patients with BCa. In this case-control study, voided urine was collected from 277 subjects including 169 BCa patients and 108 non-BCa controls. Urinary APE1/Ref-1 level was assessed by enzyme-linked immunosorbent assay (ELISA). APE1/Ref-1 levels were significantly elevated in BCa patients relative to levels in non-BCa controls and were correlated with tumor grade and stage. Urinary APE1/Ref-1 levels were also higher in patients with recurrence history of BCa. The receiver operating characteristics (ROC) curve of APE1/Ref-1 showed an area under the curve of 0.83, indicating the reliability and validity of this biomarker. The optimal combination of sensitivity and specificity was determined to be 82% and 80% at a cut-off value of 0.376 ng/100 μL for detection of APE1/Ref-1 in urine. In conclusion, urinary APE1/Ref-1 levels measured from noninvasively obtained body fluids would be clinically applicable for diagnosis of BCa.

  17. Radiochemotherapy With Cisplatin and 5-Fluorouracil After Transurethral Surgery in Patients With Bladder Cancer

    SciTech Connect

    Weiss, Christian . E-mail: Christian.Weiss@strahlen.med.uni-erlangen.de; Engehausen, Dirk G.; Krause, Frens S.; Papadopoulos, Thomas; Dunst, Juergen; Sauer, Rolf; Roedel, Claus

    2007-07-15

    Purpose: To give an update on the long-term outcome of an intensified protocol of combined radiochemotherapy (RCT) with 5-fluorouracil (5-FU) and cisplatin after initial transurethral resection of bladder tumor (TURBT) with selective organ preservation in bladder cancer. Methods and Materials: One hundred twelve patients with muscle-invading or high-risk T1 (G3, associated Tis, multifocality, diameter >5 cm) bladder cancer were enrolled in a protocol of TURBT followed by concurrent cisplatin (20 mg/m{sup 2}/day as 30-min infusion) and 5-FU (600 mg/m{sup 2}/day as 120-h continuous infusion), administered on Days 1-5 and 29-33 of radiotherapy. Response to treatment was evaluated by restaging TURBT 4-6 weeks after RCT. In case of invasive residual tumor or recurrence, salvage cystectomy was recommended. Results: Ninety-nine patients (88.4%) had no detectable tumor at restaging TURBT; 71 patients (72%) have been continuously free from local recurrence or distant metastasis. Superficial relapse occurred in 13 patients and muscle-invasive recurrence in 11 patients. Overall and cause-specific survival rates for all patients were 74% and 82% at 5 years, respectively. Of all surviving patients, 82% maintained their own bladder, 79% of whom were delighted or pleased with their urinary condition. Hematologic Grade 3/4 toxicity occurred in 23%/6% and Grade 3 diarrhea in 21% of patients. One patient required salvage cystectomy due to a shrinking bladder. Conclusion: Concurrent RCT with 5-FU/cisplatin has been associated with acceptable acute and long-term toxicity. Overall and cause-specific survival rates are encouraging. More than 80% of patients preserved their well-functioning bladder.

  18. Occupation and cancer in London: an investigation into nasal and bladder cancer using the Cancer Atlas.

    PubMed

    Baxter, P J; McDowall, M E

    1986-01-01

    The Atlas of Cancer Mortality for England and Wales showed pronounced excesses of male mortality from nasal and bladder cancer in certain London boroughs. These excesses were investigated by case-referent studies using death certificate data for male deaths, 1968-78. Nasal cancer was found to be significantly associated with occupations involving heavy exposure to wood dust. Bladder cancer was significantly associated with occupations in road transport driving and in the handling of leather, whereas consistently raised relative risk ratios were also found for wood-workers, engineering fitters, printers, machinists, plumbers, and motor mechanics. These findings highlight the potential role of occupational factors in cancer causation in London.

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

    PubMed

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

    2016-02-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

  1. M2muscarinic receptors inhibit cell proliferation and migration in urothelial bladder cancer cells

    PubMed Central

    Pacini, Luca; De Falco, Elena; Di Bari, Maria; Coccia, Andrea; Siciliano, Camilla; Ponti, Donatella; Pastore, Antonio Luigi; Petrozza, Vincenzo; Carbone, Antonio; Tata, Ada Maria; Calogero, Antonella

    2014-01-01

    The role of muscarinic receptors in several diseases including cancer has recently emerged. To evaluate the hypothesis that muscarinic acetylcholine receptors may play a role in bladder cancer as well as in other tumor types, we investigated their expression in bladder tumor specimens. All examined samples expressed the M1, M2 and M3 receptor subtypes. We also found that the level of M2 transcripts, but not those of M1 or M3, significantly increased with the tumor histologic grade. In view of these results, we proceeded to investigate whether the M2 agonist Arecaidine had any effect on in vitro cell growth and migration of T24 cells, a bladder tumor cell line expressing the muscarinic receptors, including the M2 subtype. We observed that Arecaidine significantly reduced T24 and 5637 cell proliferation and migration in a concentration dependent manner. The silencing of M2 receptor by siRNA in T24 and 5637 cell lines showed the inability of Arecaidine (100 μM) to inhibit cell proliferation after 48 hours, whereas the use of M1 and M3 antagonists in T24 appeared not to counteract the Arecaidine effect, suggesting that the inhibition of cell proliferation was directly dependent on M2 receptor activation. These data suggest that M2 muscarinic receptors may play a relevant role in bladder cancer and represent a new attractive therapeutic target. PMID:25482946

  2. Preclinical dosimetry of magnetic fluid hyperthermia for bladder cancer

    NASA Astrophysics Data System (ADS)

    Oliveira, Tiago R.; Stauffer, Paul R.; Lee, Chen-Ting; Landon, Chelsea; Etienne, Wiguins; Maccarini, Paolo F.; Inman, Brant; Dewhirst, Mark W.

    2013-02-01

    Background Despite positive efficacy, thermotherapy is not widely used in clinical oncology. Difficulties associated with field penetration and controlling power deposition patterns in heterogeneous tissue have limited its use for heating deep in the body. Heat generation using iron-oxide super-paramagnetic nanoparticles excited with magnetic fields has been demonstrated to overcome some of these limitations. The objective of this preclinical study is to investigate the feasibility of treating bladder cancer with magnetic fluid hyperthermia (MFH) by analyzing the thermal dosimetry of nanoparticle heating in a rat bladder model. Methods The bladders of 25 female rats were injected with 0.4 ml of Actium Biosystems magnetite-based nanoparticles (Actium Biosystems, Boulder CO) via catheters inserted in the urethra. To assess the distribution of nanoparticles in the rat after injection we used the 7 T small animal MRI system (Bruker ClinScan, Bruker BioSpin MRI GmbH, Ettlingen, Germany). Heat treatments were performed with a small animal magnetic field applicator (Actium Biosystems, Boulder CO) with a goal of raising bladder temperature to 42°C in <10min and maintaining for 60min. Temperatures were measured throughout the rat with seven fiberoptic temperature probes (OpSens Technologies, Quebec Canada) to characterize our ability to localize heat within the bladder target. Results The MRI study confirms the effectiveness of the catheterization procedure to homogenously distribute nanoparticles throughout the bladder. Thermal dosimetry data demonstrate our ability to controllably raise temperature of rat bladder >1°C/min to a steady-state of 42°C. Conclusion Our data demonstrate that a MFH system provides well-localized heating of rat bladder with effective control of temperature in the bladder and minimal heating of surrounding tissues.

  3. Why is perioperative chemotherapy for bladder cancer underutilized?

    PubMed

    Patafio, Francis M; Mackillop, William J; Feldman-Stewart, Deb; Siemens, David Robert; Booth, Christopher M

    2014-05-01

    Despite clinical evidence and recommendations from international treatment guidelines, the use of perioperative chemotherapy for muscle-invasive bladder cancer in routine practice remains low. Although multiple studies have described underutilization, there is an urgent need to better understand the elements contributing to the observed gaps in care. In this commentary, we explore what is known about the factors contributing to underutilization of perioperative chemotherapy for muscle-invasive bladder cancer. We also propose a framework to guide future knowledge translation activities in an effort to improve the care and outcomes of patients with this disease.

  4. Emerging Endoscopic Imaging Technologies for Bladder Cancer Detection

    PubMed Central

    Lopez, Aristeo; Liao, Joseph C.

    2014-01-01

    Modern urologic endoscopy is the result of continuous innovations since early 19th century. White light cystoscopy is the primary strategy for identification, resection, and local staging of bladder cancer. While highly effective, white light cystoscopy has several well-recognized shortcomings. Recent advances in optical imaging technologies and device miniaturization hold the potential to improve bladder cancer diagnosis and resection. Photodynamic diagnosis and narrow band imaging are the first to enter the clinical arena. Confocal laser endomicroscopy, optical coherence tomography, Raman spectroscopy, UV autofluorescence, and others have shown promising clinical and pre-clinical feasibility. We review their mechanisms of action, highlight their respective advantages, and propose future directions. PMID:24658832

  5. Nonmuscle invasive bladder cancer: a primer on immunotherapy

    PubMed Central

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

    2016-01-01

    Intravesical Bacillus Calmette-Guérin (BCG) has long been the gold standard treatment of nonmuscle invasive bladder cancer. Recently, there has been an emergence of novel immunotherapeutic agents, which have shown promise in the treatment of urothelial cell carcinoma. These agents aim to augment, modify, or enhance the immune response. Such strategies include recombinant BCG, monoclonal antibodies, vaccines, gene therapy, and adoptive T-cell therapy. Here, we review the emerging immunotherapeutics in the treatment of nonmuscle invasive bladder cancer. PMID:27458527

  6. Is gall bladder cancer a bad cancer per se?

    PubMed

    Kapoor, Vinay K

    2015-07-27

    Gall bladder cancer (GBC) has one of the poorest outcomes of all cancers. Early GBC is difficult to diagnose on even computed tomography. GB has no submucosa and the cancer infiltrates directly into the muscularis propria. GB wall is thin and important adjacent organs viz. liver, duodenum and pancreas get easily infiltrated. Tumor in the GB neck often needs extended right hepatectomy. Infiltration of duodenum/pancreas may necessitate pancreato-duodenectomy or even hepato-pancreato-duodenectomy. Mortality of surgical procedures, when performed for GBC, is higher than when performed for other cancers. Survival in GBC, even after R0 resection, is poor. There is no proven role of neo-adjuvant or adjuvant therapy for loco-regionally advanced GBC. There is no role of palliative surgery in metastatic GBC. Early GBC is diagnosed incidentally after cholecystectomy for stones and requires reoperation for completion extended cholecystectomy but unfortunately, most surgeons are not aware of this. GBC has a peculiar epidemiology and is uncommon in the West and has, therefore, not received much attention. Preventive cholecystectomy for asymptomatic stones is not recommended and there is no serum marker for screening. With all factors pitched against it, it does appear that GBC is a bad cancer per se!

  7. Is gall bladder cancer a bad cancer per se?

    PubMed Central

    Kapoor, Vinay K

    2015-01-01

    Gall bladder cancer (GBC) has one of the poorest outcomes of all cancers. Early GBC is difficult to diagnose on even computed tomography. GB has no submucosa and the cancer infiltrates directly into the muscularis propria. GB wall is thin and important adjacent organs viz. liver, duodenum and pancreas get easily infiltrated. Tumor in the GB neck often needs extended right hepatectomy. Infiltration of duodenum/pancreas may necessitate pancreato-duodenectomy or even hepato-pancreato-duodenectomy. Mortality of surgical procedures, when performed for GBC, is higher than when performed for other cancers. Survival in GBC, even after R0 resection, is poor. There is no proven role of neo-adjuvant or adjuvant therapy for loco-regionally advanced GBC. There is no role of palliative surgery in metastatic GBC. Early GBC is diagnosed incidentally after cholecystectomy for stones and requires reoperation for completion extended cholecystectomy but unfortunately, most surgeons are not aware of this. GBC has a peculiar epidemiology and is uncommon in the West and has, therefore, not received much attention. Preventive cholecystectomy for asymptomatic stones is not recommended and there is no serum marker for screening. With all factors pitched against it, it does appear that GBC is a bad cancer per se! PMID:26225192

  8. The C228T mutation of TERT promoter frequently occurs in bladder cancer stem cells and contributes to tumorigenesis of bladder cancer

    PubMed Central

    Du, Ying; He, Luyun; Cai, Zhiming; Wang, Jiansong; Fan, Zusen

    2015-01-01

    Bladder cancer is one of the most common malignant tumors worldwide. Bladder cancer stem cells (BCSCs) have been isolated recently but have not been defined yet. Here we sorted BCSCs from bladder tumor tissues or normal bladder stem cells (NBBCs) from adjacent normal bladder tissues. We found that the C228T mutation (chr5, 1, 295, 228 C > T) of TERT promoter frequently occurs in BCSCs, but not exist in NBBCs. Importantly, introducing the C228T mutation in NBBCs causes TERT overexpression and transformation of bladder cancer. Restoration of the C228T mutation to T228C in BCSCs can recover the TERT expression to a basal level and abolish tumor formation. Additionally, the C228T mutation of TERT promoter triggers TERT expression leading to increased telomerase activity. TERT expression levels are consistent with clinical severity and prognosis of bladder cancer. PMID:26143634

  9. βIII-tubulin overexpression is linked to aggressive tumor features and genetic instability in urinary bladder cancer.

    PubMed

    Hinsch, Andrea; Chaker, Aref; Burdelski, Christian; Koop, Christina; Tsourlakis, Maria Christina; Steurer, Stefan; Rink, Michael; Eichenauer, Till Simon; Wilczak, Waldemar; Wittmer, Corinna; Fisch, Margit; Simon, Ronald; Sauter, Guido; Büschek, Franziska; Clauditz, Till; Minner, Sarah; Jacobsen, Frank

    2017-03-01

    Development of genetic instability is a hallmark of tumor progression. Type III β-tubulin (TUBB3) is a component of microtubules involved in chromosome segregation. Its overexpression has been linked to adverse features of urinary bladder cancer. To investigate the role of TUBB3 for development of genetic instability, we compared TUBB3 expression with histopathological features and surrogate markers of genetic instability and tumor aggressiveness; copy number changes of HER2, TOP2A, CCND1, RAF1, and FGFR1; nuclear accumulation of p53, and cell proliferation in a tissue microarray (TMA) with more than 700 bladder cancers. TUBB3 expression was linked to high-grade and advanced-stage cancers (P<.0001), rapid cell proliferation (P<.0001), presence of multiple gene copy number alterations (P=.0008), and nuclear accumulation of p53 (P=.0008). Strong TUBB3 staining was found in 43% of urothelial cancers harboring copy number alterations as compared with 28% of genetically stable cancers, and in 50% of p53-positive cancers as compared with 30% of p53-negative tumors. The fraction of tumors with concomitant TUBB3 and p53 positivity increased with tumor stage and grade: 2% in pTaG1-2, 11% in pTaG3, 17% in pT1G2, 23% in pT1G3, and 32% in pT2-4 cancers (P<.0001). Importantly, strong TUBB3 overexpression was detectable in about 20% of low-grade, noninvasive cancers. In summary, our study demonstrates that TUBB3 overexpression is linked to an aggressive subtype of urinary bladder cancers, which is characterized by increased genetic instability, p53 alterations, and rapid cell proliferation. Detection of TUBB3 overexpression in genetically stable, low-grade, and noninvasive bladder cancers may be clinically useful to identify patients requiring particular close monitoring.

  10. Lab on a chip for multiplexed immunoassays to detect bladder cancer using multifunctional dielectrophoretic manipulations.

    PubMed

    Chuang, Cheng-Hsin; Wu, Ting-Feng; Chen, Cheng-Ho; Chang, Kai-Chieh; Ju, Jing-Wei; Huang, Yao-Wei; Van Nhan, Vo

    2015-07-21

    A multiplexed immunosensor has been developed for the detection of specific biomarkers Galectin-1 (Gal-1) and Lactate Dehydrogenase B (LDH-B) present in different grades of bladder cancer cell lysates. In order to immobilize nanoprobes with different antibodies on a single chip we employed three-step programmable dielectrophoretic manipulations for focusing, guiding and trapping to enhance the fluorescent response and reduce the interference between the two antibody arrays. The chip consisted of a patterned indium tin oxide (ITO) electrode for sensing and a middle fish bone shaped gold electrode for focusing and guiding. Using ITO electrodes for the sensing area can effectively eliminate the background noise of fluorescence response as compared to metal electrodes. It was also observed that the three step manipulation increased fluorescence response after immunosensing by about 4.6 times as compared to utilizing DEP for just trapping the nanoprobes. Two different-grade bladder cancer cell lysates (grade I: RT4 and grade III: T24) were individually analyzed for detecting the protein expression levels of Gal-1 and LDH-B. The fluorescence intensity observed for Gal-1 is higher than that of LDH-B in the T24 cell lysate; however the response observed in RT4 is higher for LDH-B as compared to Gal-1. Thus we can effectively identify the different grades of bladder cancer cells. In addition, the platform for DEP manipulation developed in this study can enable real time detection of multiple analytes on a single chip and provide more practical benefits for clinical diagnosis.

  11. Unusual presentation of metastatic gall bladder cancer.

    PubMed

    Shukla, Piyush; Roy, Soumyajit; Tiwari, Vivek; Mohanti, Bidhu K

    2014-01-01

    To report the first case of rare isolated breast metastasis from carcinoma gall bladder. Single patient case report. A 35-year-old pre-menopausal female presented with 2 * 2 cm right upper outer quadrant breast lump. Post-mastectomy, histology confirmed it to be metastatic adenocarcinoma positive for both Cytokeratin (CK) 7 and CK20. Past history as told by the patient revealed that 2 years back, cholecystectomy was performed for gall stones, of which no histology reports were present; she had a port site scar recurrence which showed it to be adenocarcinoma. Adjuvant chemotherapy and radiotherapy was advised which the patient did not complete. This is probably the first case reported of isolated breast metastasis from gall bladder carcinoma, diagnosed retrospectively. It also highlights the importance of adjuvant treatment in gall bladder malignancy.

  12. Assessment criteria for compensation of occupational bladder cancer.

    PubMed

    Schops, Wolfgang; Jungmann, Olaf; Zumbe, Jurgen; Zellner, Michael; Hengstler, Jan G; Golka, Klaus

    2013-01-01

    In Germany, more than 100 bladder tumor cases are annually recognized as occupational disease and compensated, given that medical experts regard exposure to carcinogenic aromatic amines as a likely cause of cancer. The amount of compensation is initially based on the tumor staging and grading at the time of initial diagnosis ("basic MdE") (MdE--reduction of earning capacity) and is adapted after a recurrence-free period of 2 and 5 years, respectively. In the event of treatment or tumor-related secondary conditions, the monthly compensation increases based on the severity of the objectified functional disorder. In the following article, medical experts specializing in this field provide a complete list of all known disorders, including treatment-related loss of a kidney or erectile dysfunction. In addition, the weighting of medical criteria in the assessment and calculation of the compensation is analyzed in greater detail. Since the given criteria are based on comprehensible experiences of urologists with their patients, they also provide medical experts in other countries with valuable points of reference for the calculation of the compensation.

  13. Bladder Diseases

    MedlinePlus

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

  14. Deciphering the Roles of Thiazolidinediones and PPARγ in Bladder Cancer

    PubMed Central

    Chiu, Melody; McBeth, Lucien; Sindhwani, Puneet

    2017-01-01

    The use of thiazolidinedione (TZD) therapy in type II diabetic patients has proven useful in the lowering of blood glucose levels. However, recent investigations have shown that there may be potential health concerns associated, including the risk of developing bladder cancer as well as complications in the cardiovasculature. TZDs are ligands for the nuclear receptor PPARγ, and activation causes lipid uptake and insulin sensitization, both of which are critical processes for diabetic patients whose bodies are unable to utilize insulin effectively. Several studies have shown that PPARγ/TZDs decrease IGF-1 levels and, thus, reduce cancer growth in carcinomas such as the pancreas, colon, liver, and prostate. However, other studies have shed light on the potential of the receptor as a biomarker for uroepithelial carcinomas, particularly due to its stimulatory effect on migration of bladder cancer cells. Furthermore, PPARγ may provide the tumor-promoting microenvironment by de novo synthesis of nutrients that are needed for bladder cancer development. In this review, we closely examine the TZD class of drugs and their effects on PPARγ in patient studies along with additional molecular factors that are positive modulators, such as protein phosphatase 5 (PP5), which may have considerable implications for bladder cancer therapy. PMID:28348577

  15. Update for the practicing pathologist: The International Consultation On Urologic Disease-European association of urology consultation on bladder cancer.

    PubMed

    Amin, Mahul B; Smith, Steven C; Reuter, Victor E; Epstein, Jonathan I; Grignon, David J; Hansel, Donna E; Lin, Oscar; McKenney, Jesse K; Montironi, Rodolfo; Paner, Gladell P; Al-Ahmadie, Hikmat A; Algaba, Ferran; Ali, Syed; Alvarado-Cabrero, Isabel; Bubendorf, Lukas; Cheng, Liang; Cheville, John C; Kristiansen, Glen; Cote, Richard J; Delahunt, Brett; Eble, John N; Genega, Elizabeth M; Gulmann, Christian; Hartmann, Arndt; Langner, Cord; Lopez-Beltran, Antonio; Magi-Galluzzi, Cristina; Merce, Jorda; Netto, George J; Oliva, Esther; Rao, Priya; Ro, Jae Y; Srigley, John R; Tickoo, Satish K; Tsuzuki, Toyonori; Umar, Saleem A; Van der Kwast, Theo; Young, Robert H; Soloway, Mark S

    2015-05-01

    The International Consultations on Urological Diseases are international consensus meetings, supported by the World Health Organization and the Union Internationale Contre le Cancer, which have occurred since 1981. Each consultation has the goal of convening experts to review data and provide evidence-based recommendations to improve practice. In 2012, the selected subject was bladder cancer, a disease which remains a major public health problem with little improvement in many years. The proceedings of the 2nd International Consultation on Bladder Cancer, which included a 'Pathology of Bladder Cancer Work Group,' have recently been published; herein, we provide a summary of developments and consensus relevant to the practicing pathologist. Although the published proceedings have tackled a comprehensive set of issues regarding the pathology of bladder cancer, this update summarizes the recommendations regarding selected issues for the practicing pathologist. These include guidelines for classification and grading of urothelial neoplasia, with particular emphasis on the approach to inverted lesions, the handling of incipient papillary lesions frequently seen during surveillance of bladder cancer patients, descriptions of newer variants, and terminology for urine cytology reporting.

  16. Update for the practicing pathologist: The International Consultation On Urologic Disease-European association of urology consultation on bladder cancer

    PubMed Central

    Amin, Mahul B; Smith, Steven C; Reuter, Victor E; Epstein, Jonathan I; Grignon, David J; Hansel, Donna E; Lin, Oscar; McKenney, Jesse K; Montironi, Rodolfo; Paner, Gladell P; Al-Ahmadie, Hikmat A; Algaba, Ferran; Ali, Syed; Alvarado-Cabrero, Isabel; Bubendorf, Lukas; Cheng, Liang; Cheville, John C; Kristiansen, Glen; Cote, Richard J; Delahunt, Brett; Eble, John N; Genega, Elizabeth M; Gulmann, Christian; Hartmann, Arndt; Langner, Cord; Lopez-Beltran, Antonio; Magi-Galluzzi, Cristina; Merce, Jorda; Netto, George J; Oliva, Esther; Rao, Priya; Ro, Jae Y; Srigley, John R; Tickoo, Satish K; Tsuzuki, Toyonori; Umar, Saleem A; Van der Kwast, Theo; Young, Robert H; Soloway, Mark S

    2016-01-01

    The International Consultations on Urological Diseases are international consensus meetings, supported by the World Health Organization and the Union Internationale Contre le Cancer, which have occurred since 1981. Each consultation has the goal of convening experts to review data and provide evidence-based recommendations to improve practice. In 2012, the selected subject was bladder cancer, a disease which remains a major public health problem with little improvement in many years. The proceedings of the 2nd International Consultation on Bladder Cancer, which included a ‘Pathology of Bladder Cancer Work Group,’ have recently been published; herein, we provide a summary of developments and consensus relevant to the practicing pathologist. Although the published proceedings have tackled a comprehensive set of issues regarding the pathology of bladder cancer, this update summarizes the recommendations regarding selected issues for the practicing pathologist. These include guidelines for classification and grading of urothelial neoplasia, with particular emphasis on the approach to inverted lesions, the handling of incipient papillary lesions frequently seen during surveillance of bladder cancer patients, descriptions of newer variants, and terminology for urine cytology reporting. PMID:25412849

  17. Automatic staging of bladder cancer on CT urography

    NASA Astrophysics Data System (ADS)

    Garapati, Sankeerth S.; Hadjiiski, Lubomir M.; Cha, Kenny H.; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Weizer, Alon; Alva, Ajjai; Paramagul, Chintana; Wei, Jun; Zhou, Chuan

    2016-03-01

    Correct staging of bladder cancer is crucial for the decision of neoadjuvant chemotherapy treatment and minimizing the risk of under- or over-treatment. Subjectivity and variability of clinicians in utilizing available diagnostic information may lead to inaccuracy in staging bladder cancer. An objective decision support system that merges the information in a predictive model based on statistical outcomes of previous cases and machine learning may assist clinicians in making more accurate and consistent staging assessments. In this study, we developed a preliminary method to stage bladder cancer. With IRB approval, 42 bladder cancer cases with CTU scans were collected from patient files. The cases were classified into two classes based on pathological stage T2, which is the decision threshold for neoadjuvant chemotherapy treatment (i.e. for stage >=T2) clinically. There were 21 cancers below stage T2 and 21 cancers at stage T2 or above. All 42 lesions were automatically segmented using our auto-initialized cascaded level sets (AI-CALS) method. Morphological features were extracted, which were selected and merged by linear discriminant analysis (LDA) classifier. A leave-one-case-out resampling scheme was used to train and test the classifier using the 42 lesions. The classification accuracy was quantified using the area under the ROC curve (Az). The average training Az was 0.97 and the test Az was 0.85. The classifier consistently selected the lesion volume, a gray level feature and a contrast feature. This predictive model shows promise for assisting in assessing the bladder cancer stage.

  18. Collaborating to Move Research Forward: Proceedings of the 10th Annual Bladder Cancer Think Tank.

    PubMed

    Kamat, Ashish M; Agarwal, Piyush; Bivalacqua, Trinity; Chisolm, Stephanie; Daneshmand, Sia; Doroshow, James H; Efstathiou, Jason A; Galsky, Matthew; Iyer, Gopa; Kassouf, Wassim; Shah, Jay; Taylor, John; Williams, Stephen B; Quale, Diane Zipursky; Rosenberg, Jonathan E

    2016-04-27

    The 10th Annual Bladder Cancer Think Tank was hosted by the Bladder Cancer Advocacy Network and brought together a multidisciplinary group of clinicians, researchers, representatives and Industry to advance bladder cancer research efforts. Think Tank expert panels, group discussions, and networking opportunities helped generate ideas and strengthen collaborations between researchers and physicians across disciplines and between institutions. Interactive panel discussions addressed a variety of timely issues: 1) data sharing, privacy and social media; 2) improving patient navigation through therapy; 3) promising developments in immunotherapy; 4) and moving bladder cancer research from bench to bedside. Lastly, early career researchers presented their bladder cancer studies and had opportunities to network with leading experts.

  19. Macrophage migratory inhibitory factor promotes bladder cancer progression via increasing proliferation and angiogenesis

    PubMed Central

    Taylor, John A.

    2013-01-01

    Macrophage migratory inhibitory factor (MIF) is a proinflammatory cytokine shown to promote tumorigenesis. Using the N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) model of bladder cancer, we previously showed that MIF knockout mice display decreased angiogenesis and invasion compared with wild-type. This study examines the role of MIF in bladder cancer via use of oral inhibitors of MIF. In vitro, high-grade bladder cancer cells were treated with recombinant human MIF +/− (rhMIF+/−) inhibitor. Measurements included cell counts, proliferation by 3H-thymidine incorporation (TdR), extracellular signal-regulated kinase (ERK) phosphorylation by western blot analysis, messenger RNA (mRNA) expression by quantitative PCR and protein secretion by enzyme-linked immunosorbent assay. Treatment with rhMIF increased ERK phosphorylation, cell counts, TdR and mRNA expression and protein secretion of vascular endothelial growth factor, which were blocked by specific inhibitors of ERK and MIF. In vivo, 3-month-old male C57Bl/6 mice were given BBN for 22 and 16 weeks in study 1 and study 2, respectively. Mice (n = 8–10 per group) were gavaged with vehicle or doses of MIF inhibitors daily from weeks 16–22 in both studies. Average bladder weights, reflecting tumor mass, tumor stage/burden, mitotic rate and proliferation indices, and microvessel densities were reduced in inhibitor groups versus controls. In summary, MIF promotes bladder cancer via increasing cell proliferation and angiogenesis and oral inhibitors of MIF may prove useful in treatment of this disease. PMID:23825153

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

    PubMed

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

    2011-01-01

    Urinary bladder cancer (UBC) ranks ninth in worldwide cancer. In Egypt, the pattern of bladder cancer is unique in that both the transitional and squamous cell types prevail. Despite much research on the topic, it is still difficult to predict tumor progression, optimal therapy and clinical outcome. The reduced folate carrier (RFC/SLC19A1) is the major transport system for folates in mammalian cells and tissues. RFC is also the primary means of cellular uptake for antifolate cancer chemotherapeutic drugs, however, membrane transport of antifolates by RFC is considered as limiting to antitumor activity. The purpose of this study was to compare the mRNA expression level of RFC/SLC19A1 in urothelial and non-urothelial variants of bladder carcinomas. Quantification of RFC mRNA in the mucosa of 41 untreated bladder cancer patients was performed using RT-qPCR. RFC mRNA steady-state levels were ∼9-fold higher (N = 39; 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.

  1. Diagnostic approach for cancer cells in urine sediments by 5-aminolevulinic acid-based photodynamic detection in bladder cancer.

    PubMed

    Miyake, Makito; Nakai, Yasushi; Anai, Satoshi; Tatsumi, Yoshihiro; Kuwada, Masaomi; Onishi, Sayuri; Chihara, Yoshitomo; Tanaka, Nobumichi; Hirao, Yoshihiko; Fujimoto, Kiyohide

    2014-05-01

    Bladder urothelial carcinoma is diagnosed and followed up after transurethral resection using a combination of cystoscopy, urine cytology and urine biomarkers at regular intervals. However, cystoscopy can overlook flat lesions like carcinoma in situ, and the sensitivity of urinary tests is poor in low-grade tumors. There is an emergent need for an objective and easy urinary diagnostic test for the management of bladder cancer. In this study, three different modalities for 5-aminolevulinic acid (ALA)-based photodynamic diagnostic tests were used. We developed a compact-size, desktop-type device quantifying red fluorescence in cell suspensions, named "Cellular Fluorescence Analysis Unit" (CFAU). Urine samples from 58 patients with bladder cancer were centrifuged, and urine sediments were then treated with ALA. ALA-treated sediments were subjected to three fluorescence detection assays, including the CFAU assay. The overall sensitivities of conventional cytology, BTA, NMP22, fluorescence cytology, fluorescent spectrophotometric assay and CFAU assay were 48%, 33%, 40%, 86%, 86% and 87%, respectively. Three different ALA-based assays showed high sensitivity and specificity. The ALA-based assay detected low-grade and low-stage bladder urothelial cells at shigher rate (68-80% sensitivity) than conventional urine cytology, BTA and NMP22 (8-20% sensitivity). Our findings demonstrate that the ALA-based fluorescence detection assay is promising tool for the management of bladder cancer. Development of a rapid and automated device for ALA-based photodynamic assay is necessary to avoid the variability induced by troublesome steps and low stability of specimens.

  2. Molecular targets in urothelial cancer: detection, treatment, and animal models of bladder cancer

    PubMed Central

    Smolensky, Dmitriy; Rathore, Kusum; Cekanova, Maria

    2016-01-01

    Bladder cancer remains one of the most expensive cancers to treat in the United States due to the length of required treatment and degree of recurrence. In order to treat bladder cancer more effectively, targeted therapies are being investigated. In order to use targeted therapy in a patient, it is important to provide a genetic background of the patient. Recent advances in genome sequencing, as well as transcriptome analysis, have identified major pathway components altered in bladder cancer. The purpose of this review is to provide a broad background on bladder cancer, including its causes, diagnosis, stages, treatments, animal models, as well as signaling pathways in bladder cancer. The major focus is given to the PI3K/AKT pathway, p53/pRb signaling pathways, and the histone modification machinery. Because several promising immunological therapies are also emerging in the treatment of bladder cancer, focus is also given on general activation of the immune system for the treatment of bladder cancer. PMID:27784990

  3. Status of integrated irradiation and cystectomy for bladder cancer.

    PubMed

    Whitmore, W F; Batata, M

    1984-11-01

    The rationale and representative results of integrated irradiation and cystectomy for bladder cancer are reviewed and an hypothesis regarding the mechanism and benefits of such treatment formulated. The basis for uncertainty regarding the value of preoperative irradiation is outlined and a perspective on the resolution of this uncertainty provided.

  4. Gemcitabine Hydrochloride and Eribulin Mesylate in Treating Patients With Bladder Cancer That is Advanced or Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-12-22

    Metastatic Ureteral Neoplasm; Metastatic Urethral Neoplasm; Stage III Bladder Urothelial Carcinoma; Stage III Ureter Cancer; Stage III Urethral Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Ureter Cancer; Stage IV Urethral Cancer; Ureter Urothelial Carcinoma; Urethral Urothelial Carcinoma

  5. Pathway analysis of bladder cancer genome-wide association study identifies novel pathways involved in bladder cancer development

    PubMed Central

    Chen, Meng; Rothman, Nathaniel; Ye, Yuanqing; Gu, Jian; Scheet, Paul A.; Huang, Maosheng; Chang, David W.; Dinney, Colin P.; Silverman, Debra T.; Figueroa, Jonine D.; Chanock, Stephen J.; Wu, Xifeng

    2016-01-01

    Genome-wide association studies (GWAS) are designed to identify individual regions associated with cancer risk, but only explain a small fraction of the inherited variability. Alternative approach analyzing genetic variants within biological pathways has been proposed to discover networks of susceptibility genes with additional effects. The gene set enrichment analysis (GSEA) may complement and expand traditional GWAS analysis to identify novel genes and pathways associated with bladder cancer risk. We selected three GSEA methods: Gen-Gen, Aligator, and the SNP Ratio Test to evaluate cellular signaling pathways involved in bladder cancer susceptibility in a Texas GWAS population. The candidate genetic polymorphisms from the significant pathway selected by GSEA were validated in an independent NCI GWAS. We identified 18 novel pathways (P < 0.05) significantly associated with bladder cancer risk. Five of the most promising pathways (P ≤ 0.001 in any of the three GSEA methods) among the 18 pathways included two cell cycle pathways and neural cell adhesion molecule (NCAM), platelet-derived growth factor (PDGF), and unfolded protein response pathways. We validated the candidate polymorphisms in the NCI GWAS and found variants of RAPGEF1, SKP1, HERPUD1, CACNB2, CACNA1C, CACNA1S, COL4A2, SRC, and CACNA1C were associated with bladder cancer risk. Two CCNE1 variants, rs8102137 and rs997669, from cell cycle pathways showed the strongest associations; the CCNE1 signal at 19q12 has already been reported in previous GWAS. These findings offer additional etiologic insights highlighting the specific genes and pathways associated with bladder cancer development. GSEA may be a complementary tool to GWAS to identify additional loci of cancer susceptibility. PMID:27738493

  6. System-Level Biochip for Impedance Sensing and Programmable Manipulation of Bladder Cancer Cells

    PubMed Central

    Chuang, Cheng-Hsin; Huang, Yao-Wei; Wu, Yao-Tung

    2011-01-01

    This paper develops a dielectrophoretic (DEP) chip with multi-layer electrodes and a micro-cavity array for programmable manipulations of cells and impedance measurement. The DEP chip consists of an ITO top electrode, flow chamber, middle electrode on an SU-8 surface, micro-cavity arrays of SU-8 and distributed electrodes at the bottom of the micro-cavity. Impedance sensing of single cells could be performed as follows: firstly, cells were trapped in a micro-cavity array by negative DEP force provided by top and middle electrodes; then, the impedance measurement for discrimination of different stage of bladder cancer cells was accomplished by the middle and bottom electrodes. After impedance sensing, the individual releasing of trapped cells was achieved by negative DEP force using the top and bottom electrodes in order to collect the identified cells once more. Both cell manipulations and impedance measurement had been integrated within a system controlled by a PC-based LabVIEW program. In the experiments, two different stages of bladder cancer cell lines (grade III: T24 and grade II: TSGH8301) were utilized for the demonstration of programmable manipulation and impedance sensing; as the results show, the lower-grade bladder cancer cells (TSGH8301) possess higher impedance than the higher-grade ones (T24). In general, the multi-step manipulations of cells can be easily programmed by controlling the electrical signal in our design, which provides an excellent platform technology for lab-on-a-chip (LOC) or a micro-total-analysis-system (Micro TAS). PMID:22346685

  7. Urinary pH, cigarette smoking and bladder cancer risk

    PubMed Central

    Alguacil, Juan; Kogevinas, Manolis; Silverman, Debra T.; Malats, Núria; Real, Francisco X.; García-Closas, Montserrat; Tardón, Adonina; Rivas, Manuel; Torà, Montserrat; García-Closas, Reina; Serra, Consol; Carrato, Alfredo; Pfeiffer, Ruth M.; Fortuny, Joan; Samanic, Claudine; Rothman, Nathaniel

    2011-01-01

    Glucuronide conjugates of 4-aminobiphenyl and its N-hydroxy metabolite can be rapidly hydrolyzed in acidic urine to undergo further metabolic activation and form DNA adducts in the urothelium. We conducted a large multicenter case–control study in Spain to explore the etiology of bladder cancer and evaluated the association between urine pH and bladder cancer risk, alone and in combination with cigarette smoking. In total, 712 incident urothelial cell carcinoma cases and 611 hospital controls directly measured their urine pH with dipsticks twice a day (first void in the morning and early in the evening) during four consecutive days 2 weeks after hospital discharge. We found that a consistently acidic urine pH ≤6.0 was associated with an increased risk of bladder cancer [odds ratio (OR) = 1.5, 95% confidence interval (CI): 1.2–1.9] compared with all other subjects. Furthermore, risk estimates for smoking intensity and risk of bladder cancer among current smokers tended to be higher for those with a consistently acidic urine (OR = 8.8, 11.5 and 23.8) compared with those without (OR = 4.3, 7.7 and 5.8, respectively, for 1–19, 20–29 and 30+ cigarettes per day; Pinteraction for 30+ cigarettes per day = 0.024). These results suggest that urine pH, which is determined primarily by diet and body surface area, may be an important modifier of smoking and risk of bladder cancer. PMID:21402590

  8. Role of Sonic Hedgehog (Shh) Signaling in Bladder Cancer Stemness and Tumorigenesis.

    PubMed

    Syed, Islam S; Pedram, Akbari; Farhat, Walid A

    2016-02-01

    Sonic hedgehog (Shh) signaling pathway has emerged as a critical component of bladder development, cancer initiation, and progression. While the role of Shh signaling in bladder development is well documented, its role in bladder cancer progression is uncertain. Additionally, epithelial-to-mesenchymal transition (EMT) has been identified to promote bladder cancer progression in the initial stages and also contribute to drug resistance in the later stage and ultimately metastasis. We speculate that epithelial-to-mesenchymal transitions (EMT) and Shh fuel the carcinogenesis process. This review presents the most recent studies focusing on the role of Shh signaling in bladder cancer progression.

  9. shRNA targeting long non-coding RNA CCAT2 controlled by tetracycline-inducible system inhibits progression of bladder cancer cells.

    PubMed

    Li, Jianfa; Zhuang, Chengle; Liu, Yuchen; Chen, Mingwei; Zhou, Qing; Chen, Zhicong; He, Anbang; Zhao, Guoping; Guo, Yinglu; Wu, Hanwei; Cai, Zhiming; Huang, Weiren

    2016-05-17

    Recent reports show that long non-coding RNAs (lncRNAs) are emerging as significant functional regulators in the development of tumors, including bladder cancer. Here, we found that CCAT2 was upregulated in bladder cancer tissues and cell lines. Through the statistical analyses, we also found that the high expression level of CCAT2 was positively correlated with histological grade and TNM stage of bladder cancer. Further experimental results revealed that knockdown of CCAT2 could decrease cell proliferation and migration as well as induce apoptosis in bladder cancer cells. Besides, using the post-transcriptional device of synthetic biology, we create the tetracycline-inducible double small hairpin RNAs (shRNAs) vector to control the expression level of CCAT2 which was induced by doxycycline in a dosage-dependent manner. In summary, our data indicated that CCAT2 may be an oncogene and a therapeutic target in bladder cancer. The expression of CCAT2 can be quantitatively controlled by the synthetic "tetracycline-on" switch system in bladder cancer in response to different concentrations of doxycycline to inhibit the development of bladder cancer cells.

  10. Concurrence of villous adenoma and non-muscle invasive bladder cancer arising in the bladder: a case report and review of the literature

    PubMed Central

    2013-01-01

    Background Villous adenoma arising in the urinary tract is rare tumor. Most cases have been identified as benign neoplasm in the colon. Villous adenoma of the gastrointestinal tract is thought arise from premalignant polyps. Here, we report a case of concurrence of villous adenoma and non-muscle invasive bladder cancer. Case presentation An 85-year-old woman presented at our office because of gross hematuria. Cystoscopic examination detected two papillary tumors in the bladder. Each tumor was resected and diagnosed, respectively. Histopathology confirmed that the resected one tumor was a villous adenoma, and the other was urothelial carcinoma (T1, high grade). Immunostaining for cytokeratin (CK) 7, CK20 and Ki-67 confirmed that CK7: (−), CK20: (+) and Ki-67: (<=30%) in villous adenoma while CK7: (+), CK20: (+), and Ki-67: (70%) in urothelial carcinoma. Three months later from TUR, urothelial carcinoma recurred in the trigone. She received adjuvant intravesical immunotherapy with BCG post TUR for the recurrence site. Conclusion There were no specific findings on ultrasonography, CT, MRI or cystoscopic examination morphologically. Therefore, pre-pathological villous adenoma of the bladder is extremely difficult to diagnose. There are some case reports of solitary villous adenoma in the bladder or with coexisting adeno carcinoma. However, to the best of our knowledge, this is only the second report of villous adenoma in the bladder of coexisting urothelial carcinoma that has been published in the literature. Premalignant villous adenoma of the bladder is extremely rare and difficult to diagnose without histologic examination. Any suspicious lesion of the bladder should be biopsied and/or resected to confirm histology. PMID:23870731

  11. Imatinib radiosensitises bladder cancer by targeting homologous recombination

    PubMed Central

    Qiao, Boling; Kerr, Martin; Groselj, Blaz; Teo, Mark TW; Knowles, Margaret A; Bristow, Robert G; Phillips, Roger M; Kiltie, Anne E

    2013-01-01

    Radiotherapy is a major treatment modality used to treat muscle-invasive bladder cancer, with patient outcomes similar to surgery. However, radioresistance is a significant factor in treatment failure. Cell-free extracts of muscle-invasive bladder tumours are defective in non-homologous end-joining (NHEJ), and this phenotype might be exploited clinically by combining radiotherapy with a radiosensitising drug that targets homologous recombination (HR), thereby sparing normal tissues with intact NHEJ. The response of the HR protein RAD51 to radiation is inhibited by the small molecule tyrosine kinase inhibitor (TKI) imatinib. Stable RT112 bladder cancer Ku knockdown (Ku80KD) cells were generated using shRNA technology to mimic the invasive tumour phenotype, and also RAD51 knockdown (RAD51KD) cells to demonstrate imatinib’s pathway selectivity. Ku80KD, RAD51KD, non-silencing vector control and parental RT112 cells were treated with radiation in combination with either imatinib or lapatinib, which inhibits NHEJ, and cell survival assessed by clonogenic assay. Drug doses were chosen at approximately IC40 and IC10 (non-toxic) levels. Imatinib radiosensitised Ku80KD cells to a greater extent than RAD51KD or RT112 cells. In contrast, lapatinib radiosensitised RAD51KD and RT112 cells, but not Ku80KD cells. Taken together, our findings suggest a new application for imatinib in concurrent use with radiotherapy to treat muscle-invasive bladder cancer. PMID:23302228

  12. How to optimally manage elderly bladder cancer patients?

    PubMed

    Soria, Francesco; Moschini, Marco; Korn, Stephan; Shariat, Shahrokh F

    2016-10-01

    Bladder cancer (BCa) is a disease of the elderly and as the population is aging, BCa will become an even bigger public health challenge in the future. Nowadays the correct management of BCa in the elderly remains controversial. The purpose of this article was to review the previous literature to summarize the current knowledge. Using Medline, a non-systematic review was performed including articles between January 2000 and February 2016 in order to describe the management of BCa in the elderly in all its aspects. English language original articles, reviews and editorials were selected based on their clinical relevance. In the literature, the definition of elderly is variable and based on chronological, not biological, age. BCa seems to be more aggressive in the elderly. The management of non-muscle invasive bladder cancer (NMIBC) does not strongly differ from younger patients, except for the role of adjuvant immunotherapy. In patients with muscle invasive bladder cancer (MIBC) the role of a multidisciplinary geriatric evaluation is potentially beneficial. The curative treatment in MIBC remains radical cystectomy (RC) and elderly patients should not be withheld a potentially life-saving intervention only based on chronological age. Patients unsuitable to a major surgical approach may be eligible for bladder-sparing techniques. Geriatric assessment could help identify the frail elderly and customize their perioperative care (i.e., pre and re habilitation). In conclusion the treatment of BCa in the elderly has to be patient-centered and focused on biological age and functional reserves.

  13. How to optimally manage elderly bladder cancer patients?

    PubMed Central

    Soria, Francesco; Moschini, Marco; Korn, Stephan

    2016-01-01

    Bladder cancer (BCa) is a disease of the elderly and as the population is aging, BCa will become an even bigger public health challenge in the future. Nowadays the correct management of BCa in the elderly remains controversial. The purpose of this article was to review the previous literature to summarize the current knowledge. Using Medline, a non-systematic review was performed including articles between January 2000 and February 2016 in order to describe the management of BCa in the elderly in all its aspects. English language original articles, reviews and editorials were selected based on their clinical relevance. In the literature, the definition of elderly is variable and based on chronological, not biological, age. BCa seems to be more aggressive in the elderly. The management of non-muscle invasive bladder cancer (NMIBC) does not strongly differ from younger patients, except for the role of adjuvant immunotherapy. In patients with muscle invasive bladder cancer (MIBC) the role of a multidisciplinary geriatric evaluation is potentially beneficial. The curative treatment in MIBC remains radical cystectomy (RC) and elderly patients should not be withheld a potentially life-saving intervention only based on chronological age. Patients unsuitable to a major surgical approach may be eligible for bladder-sparing techniques. Geriatric assessment could help identify the frail elderly and customize their perioperative care (i.e., pre and re habilitation). In conclusion the treatment of BCa in the elderly has to be patient-centered and focused on biological age and functional reserves. PMID:27785425

  14. Controversies and challenges in research on urogenital schistosomiasis-associated bladder cancer

    PubMed Central

    Honeycutt, Jared; Hammam, Olfat; Fu, Chi-Ling; Hsieh, Michael H.

    2014-01-01

    Urogenital schistosomiasis, infection with Schistosoma haematobium, is linked to increased risk for the development of bladder cancer, but the importance of various mechanisms responsible for this association remains unclear, in part due to lack of sufficient and appropriate animal models. New advances in the study of this parasite, bladder regenerative processes, and human schistosomal bladder cancers may shed new light on the complex biological processes that connect S. haematobium infection to bladder carcinogenesis. PMID:24913983

  15. Partial allelotype of schistosomiasis-associated bladder cancer.

    PubMed

    Shaw, M E; Elder, P A; Abbas, A; Knowles, M A

    1999-03-01

    In Egypt and other regions of the Middle East where the trematode Schistosoma haematobium is endemic, bladder cancer is the most common adult cancer. Unlike bladder cancers in Western countries, which are predominantly transitional-cell carcinoma (TCC), these schistosomiasis-associated bladder cancers are predominantly squamous-cell carcinoma (SCC). Our aim was to assess a large series of schistosomiasis-associated bladder tumours for genetic alterations commonly found in TCC in the United Kingdom and the United States. We have carried out a partial allelotype of 70 tumours from patients with schistosomiasis. LOH was found on all chromosome arms studied (3p, 4p, 4q, 8p, 9p, 9q, 11p, 11q, 13q, 14q, 17p, 18q). The most frequent regions of LOH were 9p (65%), 17p (58%), 3p (40%), 9q (39%) and 8p (37%). LOH on 17p, where the TP53 gene is located, was more common in Egyptian TCC than in SCC. Similarly, 8p LOH was more common in TCC than SCC. The most striking difference between this group of tumours and TCCs from the United Kingdom and the United States was the high frequency of 9p LOH in the region of the CDKN2 gene (65%) and the relatively low frequency of 9q LOH (39%); 15 of 43 tumours with LOH of at least one marker on chromosome 9 showed LOH of 9p only. This suggests that a 9p gene, possibly CDKN2, may contribute to the development of the majority of schistosomiasis-associated bladder tumours but that genes on 9q play a much less important role.

  16. Tetracycline-inducible shRNA targeting antisense long non-coding RNA HIF1A-AS2 represses the malignant phenotypes of bladder cancer.

    PubMed

    Chen, Mingwei; Zhuang, Chengle; Liu, Yuchen; Li, Jianfa; Dai, Fen; Xia, Ming; Zhan, Yonghao; Lin, Junhao; Chen, Zhicong; He, Anbang; Xu, Wen; Zhao, Guoping; Guo, Yinglu; Cai, Zhiming; Huang, Weiren

    2016-06-28

    Various studies have indicated that long non-coding RNAs (lncRNAs) play vital roles in the cancer development and progression. LncRNA hypoxia inducible factor 1alpha antisense RNA-2 (HIF1A-AS2) is upregulated in gastric carcinomas and knockdown of HIF1A-AS2 expression by siRNA could inhibit cell proliferation in vitro and tumorigenesis in vivo. Inspired by these observations, we hypothesized that HIF1A-AS2 possibly plays the analogous roles in bladder cancer. In our study, we first reported that HIF1A-AS2 was up-regulated in bladder cancer tissues and cells, and HIF1A-AS2 expression level in bladder cancer tissues is positively associated with advanced clinical pathologic grade and TNM phase. Cell proliferation inhibition, cell migration suppression and apoptosis induction were observed by silencing HIF1A-AS2 in bladder cancer T24 and 5637 cells. Overexpression of HIF1A-AS2 in SV-HUC-1 cells could promote cell proliferation, cell migration and anti-apoptosis. Besides, we utilized the emerging technology of medical synthetic biology to design tetracycline-inducible small hairpin RNA (shRNA) vector which specifically silenced HIF1A-AS2 in a dosage-dependent manner to inhibit the progression of human bladder cancer. In conclusion, our data suggested that HIF1A-AS2 plays oncogenic roles and can be used as a therapeutic target for treating human bladder cancer. Synthetic "tetracycline-on" switch system that quantitatively controlled the expression of HIF1A-AS2 in bladder cancer can inhibit the progression of bladder cancer cells in a dosage-dependent manner. Our findings provide new insights into the role of the lncRNA HIF1A-AS2 in the bladder cancer.

  17. Biomarkers for detection and surveillance of bladder cancer

    PubMed Central

    Budman, Lorne I; Kassouf, Wassim; Steinberg, Jordan R

    2008-01-01

    Introduction Bladder cancer is the fourth most common cancer in men and the ninth most common cancer in women in Canada. Early detection of tumours is essential for improved prognosis and long-term survival. The standard method for detection and surveillance is cystoscopy together with urine cytology. Cystoscopy is relatively sensitive but is expensive and invasive. Urinary cytology is a noninvasive method that has poor sensitivity but high specificity; it is relied on for the detection of carcinoma in situ. Currently, several urinary-based bladder tumour biomarkers with USFDA/Health Canada approval are available commercially, but none have been widely adopted by urologists despite their offering high sensitivity and/or specificity. We present here a review of recent studies evaluating 7 commercial biomarker assays for the detection and/or surveillance of bladder cancer. Results Sensitivity and specificity ranges, respectively, for each marker were reported as follows: BTA Stat (Polymedco), 52.5%–78.0% and 69.0%–87.1%; BTA Trak (Polymedco), 51%–100% and 73%–92.5%; cytology, 12.1%–84.6% and 78.0%–100%; hematuria dipstick, 47.0%–92.6% and 51.0%–84.0%; NMP22 Bladder Cancer Test (Matritech), 34.6%–100% and 60.0%–95.0%; NMP22 BladderChek (Matritech), 49.5%–65.0% and 40.0%–89.8%; ImmunoCyt/uCyt+ (DiagnoCure), 63.3%–84.9% and 62.0%–78.1%; ImmunoCyt/uCyt+ and cytology, 81.0%–89.3% and 61.0%–77.7%; and UroVysion (Abbott Molecular)/florescence in situ hybridization, 68.6%–100% and 65.0%–96.0%. Conclusion We find that no currently available bladder cancer urinary marker is sensitive enough to eliminate the need for cystoscopy. In addition, cytology remains integral to the detection of occult cancer. However, owing to their relatively high sensitivities, these markers may be used to extend the period between cystoscopies in the surveillance of patients with transitional cell carcinoma. Further study is required to determine which markers

  18. KISS1 methylation and expression as tumor stratification biomarkers and clinical outcome prognosticators for bladder cancer patients.

    PubMed

    Cebrian, Virginia; Fierro, Marta; Orenes-Piñero, Esteban; Grau, Laura; Moya, Patricia; Ecke, Thorsten; Alvarez, Miguel; Gil, Marta; Algaba, Ferran; Bellmunt, Joaquin; Cordon-Cardo, Carlos; Catto, James; López-Beltrán, Antonio; Sánchez-Carbayo, Marta

    2011-08-01

    KISS1 is a metastasis suppressor gene that is lost in several malignancies, including bladder cancer. We tested the epigenetic silencing hypothesis and evaluated the biological influence of KISS1 methylation on its expression and clinical relevance in bladder cancer. KISS1 hypermethylation was frequent in bladder cancer cells analyzed by methylation-specific PCR and bisulfite sequencing and was associated with low gene expression, being restored in vitro by demethylating azacytidine. Hypermethylation was also frequently observed in a large series of bladder tumors (83.1%, n = 804). KISS1 methylation was associated with increasing stage (P = 0.001) and tumor grade (P = 0.010). KISS1 methylation was associated with low KISS1 transcript expression by quantitative RT-PCR (P = 0.037). KISS1 transcript expression was also associated with histopathological tumor stage (P < 0.0005). Low transcript expression alone (P = 0.003) or combined with methylation (P = 0.019) was associated with poor disease-specific survival (n = 205). KISS1 transcript expression remained an independent prognosticator in multivariate analyses (P = 0.017). KISS1 hypermethylation was identified in bladder cancer, providing a potential mechanistic explanation (epigenetic silencing) for the observed loss of KISS1 in uroepithelial malignancies. Associations of KISS1 methylation and its expression with histopathological variables and poor survival suggest the utility of incorporating KISS1 measurement using paraffin-embedded material for tumor stratification and clinical outcome prognosis of patients with uroepithelial neoplasias.

  19. PAK5 mediates cell: cell adhesion integrity via interaction with E-cadherin in bladder cancer cells.

    PubMed

    Ismail, Ahmad Fahim; Oskay Halacli, Sevil; Babteen, Nouf; De Piano, Mario; Martin, Tracey A; Jiang, Wen G; Khan, Muhammad Shamim; Dasgupta, Prokar; Wells, Claire M

    2017-03-24

    Urothelial bladder cancer is a major cause of morbidity and mortality worldwide, causing an estimated 150 000 deaths per year. Whilst non-muscle-invasive bladder tumours can be effectively treated, with high survival rates, many tumours recur, and some will progress to muscle-invasive disease with a much poorer long-term prognosis. Thus, there is a pressing need to understand the molecular transitions occurring within the progression of bladder cancer to an invasive disease. Tumour invasion is often associated with a down-regulation of E-cadherin expression concomitant with a suppression of cell:cell junctions, and decreased levels of E-cadherin expression have been reported in higher grade urothelial bladder tumours. We find that expression of E-cadherin in a panel of bladder cancer cell lines correlated with the presence of cell:cell junctions and the level of PAK5 expression. Interestingly, exogenous PAK5 has recently been described to be associated with cell:cell junctions and we now find that endogenous PAK5 is localised to cell junctions and interacts with an E-cadherin complex. Moreover, depletion of PAK5 expression significantly reduced junctional integrity. These data suggest a role for PAK5 in maintaining junctional stability and we find that, in both our own patient samples and a commercially available dataset, PAK5mRNA levels are reduced in human bladder cancer compared with normal controls. Taken together, the present study proposes that PAK5 expression levels could be used as a novel prognostic marker for bladder cancer progression.

  20. PTPD1 Supports Receptor Stability and Mitogenic Signaling in Bladder Cancer Cells*

    PubMed Central

    Carlucci, Annalisa; Porpora, Monia; Garbi, Corrado; Galgani, Mario; Santoriello, Margherita; Mascolo, Massimo; di Lorenzo, Domenico; Altieri, Vincenzo; Quarto, Maria; Terracciano, Luigi; Gottesman, Max E.; Insabato, Luigi; Feliciello, Antonio

    2010-01-01

    PTPD1, a cytosolic non-receptor protein-tyrosine phosphatase, stimulates the Src-EGF transduction pathway. Localization of PTPD1 at actin cytoskeleton and adhesion sites is required for cell scattering and migration. Here, we show that during EGF stimulation, PTPD1 is rapidly recruited to endocytic vesicles containing the EGF receptor. Endosomal localization of PTPD1 is mediated by interaction with KIF16B, an endosomal kinesin that modulates receptor recycling at the plasma membrane. Silencing of PTPD1 promotes degradation of EGF receptor and inhibits downstream ERK signaling. We also found that PTPD1 is markedly increased in bladder cancer tissue samples. PTPD1 levels positively correlated with the grading and invasiveness potential of these tumors. Transgenic expression of an inactive PTPD1 mutant or genetic knockdown of the endogenous PTPD1 severely inhibited both growth and motility of human bladder cancer cells. These findings identify PTPD1 as a novel component of the endocytic machinery that impacts on EGF receptor stability and on growth and motility of bladder cancer cells. PMID:20923765

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

    PubMed Central

    Ohishi, Tomokazu; Koga, Fumitaka; Migita, Toshiro

    2015-01-01

    Bladder cancer (BC), the most common cancer arising from the human urinary tract, consists of two major clinicopathological phenotypes: muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). MIBC frequently metastasizes and is associated with an unfavorable prognosis. A certain proportion of patients with metastatic BC can achieve a remission with systemic chemotherapy; however, the disease relapses in most cases. Evidence suggests that MIBC comprises a small population of cancer stem cells (CSCs), which may be resistant to these treatments and may be able to form new tumors in the bladder or other organs. Therefore, the unambiguous identification of bladder CSCs and the development of targeted therapies are urgently needed. Nevertheless, it remains unclear where bladder CSCs originate and how they are generated. We review recent studies on bladder CSCs, specifically focusing on their proposed origin and the possible therapeutic options based on the CSC theory. PMID:26729098

  2. Polymorphisms in DNA repair genes, smoking, and bladder cancer risk: findings from the International Consortium of Bladder Cancer

    PubMed Central

    Stern, Mariana C.; Lin, Jie; Figueroa, Jonine D.; Kelsey, Karl T.; Kiltie, Anne E.; Yuan, Jian-Min; Matullo, Giuseppe; Fletcher, Tony; Benhamou, Simone; Taylor, Jack A.; Placidi, Donatella; Zhang, Zuo-Feng; Steineck, Gunnar; Rothman, Nathaniel; Kogevinas, Manolis; Silverman, Debra; Malats, Nuria; Chanock, Stephen; Wu, Xifeng; Karagas, Margaret R.; Andrew, Angeline S.; Nelson, Heather H.; Bishop, D. Timothy; Sak, Sei Chung; Choudhury, Ananya; Barrett, Jennifer H; Elliot, Faye; Corral, Román; Joshi, Amit D.; Gago-Dominguez, Manuela; Cortessis, Victoria K.; Xiang, Yong-Bing; Vineis, Paolo; Sacerdote, Carlotta; Guarrera, Simonetta; Polidoro, Silvia; Allione, Alessandra; Gurzau, Eugen; Koppova, Kvetoslava; Kumar, Rajiv; Rudnai, Peter; Porru, Stefano; Carta, Angela; Campagna, Marcello; Arici, Cecilia; Park, SungShim Lani; Garcia-Closas, Montserrat

    2009-01-01

    Tobacco smoking is the most important and well-established bladder cancer risk factor, and a rich source of chemical carcinogens and reactive oxygen species that can induce damage to DNA in urothelial cells. Therefore, common variation in DNA repair genes might modify bladder cancer risk. In this study we present results from meta- and pooled analyses conducted as part of the International Consortium of Bladder Cancer. We included data on 10 single nucleotide polymorphisms corresponding to 7 DNA repair genes from 13 studies. Pooled- and meta-analyses included 5,282 cases and 5,954 controls of non-Latino white origin. We found evidence for weak but consistent associations with ERCC2 D312N (rs1799793) (per allele OR = 1.10; 95% CI = 1.01–1.19; p = 0.021), NBN E185Q (rs1805794) (per allele OR = 1.09; 95% CI = 1.01–1.18; p = 0.028), and XPC A499V (rs2228000) (per allele OR = 1.10; 95% CI = 1.00–1.21, p = 0.044). The association with NBN E185Q was limited to ever smokers (interaction p = 0.002), and was strongest for the highest levels of smoking dose and smoking duration. Overall, our study provides the strongest evidence to date for a role of common variants in DNA repair genes in bladder carcinogenesis. PMID:19706757

  3. Sonic hedgehog (Shh) signaling promotes tumorigenicity and stemness via activation of epithelial-to-mesenchymal transition (EMT) in bladder cancer.

    PubMed

    Islam, S S; Mokhtari, R B; Noman, A S; Uddin, M; Rahman, M Z; Azadi, M A; Zlotta, A; van der Kwast, T; Yeger, H; Farhat, W A

    2016-05-01

    Activation of the sonic hedgehog (Shh) signaling pathway controls tumorigenesis in a variety of cancers. Here, we show a role for Shh signaling in the promotion of epithelial-to-mesenchymal transition (EMT), tumorigenicity, and stemness in the bladder cancer. EMT induction was assessed by the decreased expression of E-cadherin and ZO-1 and increased expression of N-cadherin. The induced EMT was associated with increased cell motility, invasiveness, and clonogenicity. These progression relevant behaviors were attenuated by treatment with Hh inhibitors cyclopamine and GDC-0449, and after knockdown by Shh-siRNA, and led to reversal of the EMT phenotype. The results with HTB-9 were confirmed using a second bladder cancer cell line, BFTC905 (DM). In a xenograft mouse model TGF-β1 treated HTB-9 cells exhibited enhanced tumor growth. Although normal bladder epithelial cells could also undergo EMT and upregulate Shh with TGF-β1 they did not exhibit tumorigenicity. The TGF-β1 treated HTB-9 xenografts showed strong evidence for a switch to a more stem cell like phenotype, with functional activation of CD133, Sox2, Nanog, and Oct4. The bladder cancer specific stem cell markers CK5 and CK14 were upregulated in the TGF-β1 treated xenograft tumor samples, while CD44 remained unchanged in both treated and untreated tumors. Immunohistochemical analysis of 22 primary human bladder tumors indicated that Shh expression was positively correlated with tumor grade and stage. Elevated expression of Ki-67, Shh, Gli2, and N-cadherin were observed in the high grade and stage human bladder tumor samples, and conversely, the downregulation of these genes were observed in the low grade and stage tumor samples. Collectively, this study indicates that TGF-β1-induced Shh may regulate EMT and tumorigenicity in bladder cancer. Our studies reveal that the TGF-β1 induction of EMT and Shh is cell type context dependent. Thus, targeting the Shh pathway could be clinically beneficial in the

  4. Evaluation Of The Contact Nd:Yag Laser Therapy For Bladder Cancer

    NASA Astrophysics Data System (ADS)

    Washida, Hiroto; Watanabe, Hideki; Noguchi, Yukinori; Sasaki, Syoichi; Hori, Takeshi

    1989-09-01

    Transurethral laser destruction using contact Nd:YAG laser (TULD) was performed on 96 occasions in 72 patients from February 1984 to December 1987. For the purpose of cure, TULD was undertaken on 59 occasions in 37 patients with primary bladder cancer. In the 59 occasions, usefulness of the TULD was evaluated. The cancers were classfied and staged in accordance with the Japanese Urological Association. The usefulness of the TULD was judged by surgeons with criteria as follows: degree of difficulty of manipulation, degree of destruction of the cancers, and bleeding during the TULD. Features of the cancers, for which the TULD was judged as useful, were summarized as follows: 1. On cystoscopical findings, the form of the cancer was superficial, the number of cancers were under the number of four and the sizes of the cancers were under 3 cm in diameter. 2. On pathological findings, the grade of the cancers reached grade II and the stage of the cancers reached stage T1.

  5. Ten genetic polymorphisms in bladder cancer.

    PubMed Central

    Cartwright, R A; Adib, R; Appleyard, I; Coxon, J G; Glashan, R W; Richards, B; Robinson, M R; Sunderland, E; Barham-Hall, D

    1983-01-01

    Data are presented on a group of cases of primary carcinoma of the bladder, detailing red cell surface blood group antigenic phenotypes, serum haptoglobin phenotypes, and some red cell isoenzyme phenotypes. Account is taken of the stage of the disease at presentation. The results are compared with corresponding phenotype frequencies in groups of presumed healthy persons originating either in Yorkshire or County Durham. Differences in relative incidences were found in the haptoglobin, phosphoglucomutase (PGM), and some other systems. These are both differences between all cases and controls and between particular stages at presentation and controls. PMID:6221102

  6. Organic cation secretion by Cancer borealis urinary bladder

    SciTech Connect

    Miller, D.S.; Holliday, C.W.

    1987-01-01

    In the crab, Cancer borealis, initial clearance studies showed a potent renal excretory system for the model organic cation, tetraethylammonium (TEA). (/sup 14/C)-TEA clearance averaged 145 +/- 32 ml/day, which was 18 times the paired polyethylene glycol clearance. TEA uptake by slices of urinary bladder was concentrative, saturable, inhibitable by N/sup 1/-methylnicotinamide chloride, and dependent on glycolytic, but not oxidative, metabolism. When mounted in flux chambers, bladders exhibited a large net secretory flux. For 0.1 mM TEA, the ratio of secretory to reabsorptive fluxes was 65. Urinary bladders from another crab, Cancer irroratus, and a lobster, Homarus americanus, also exhibited net TEA secretion. In C. borealis bladder, secretory transport was concentrative, saturable, and nearly abolished by addition of 1 mM quinine to the serosol bath. Reabsorptive transport was not concentrative and was not reduced by luminal quinine. The data are consistent with a secretory pathway that is transcellular and mediated by carriers at both the serosal and luminal membranes.

  7. Occupation and cancer in London: an investigation into nasal and bladder cancer using the Cancer Atlas.

    PubMed Central

    Baxter, P J; McDowall, M E

    1986-01-01

    The Atlas of Cancer Mortality for England and Wales showed pronounced excesses of male mortality from nasal and bladder cancer in certain London boroughs. These excesses were investigated by case-referent studies using death certificate data for male deaths, 1968-78. Nasal cancer was found to be significantly associated with occupations involving heavy exposure to wood dust. Bladder cancer was significantly associated with occupations in road transport driving and in the handling of leather, whereas consistently raised relative risk ratios were also found for wood-workers, engineering fitters, printers, machinists, plumbers, and motor mechanics. These findings highlight the potential role of occupational factors in cancer causation in London. Images PMID:3947560

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

    SciTech Connect

    Tunio, Mutahir A.; Hashmi, Altaf; Qayyum, Abdul; Mohsin, Rehan; Zaeem, Ahmed

    2012-03-01

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

  9. Significance of a minor high-grade component in a low-grade noninvasive papillary urothelial carcinoma of bladder.

    PubMed

    Reis, Leonardo O; Taheri, Diana; Chaux, Alcides; Guner, Gunes; Mendoza Rodriguez, Maria A; Bivalacqua, Trinity J; Schoenberg, Mark P; Epstein, Jonathan I; Netto, George J

    2016-01-01

    To assess the clinicopathological features and prognostic significance of the presence of 5% or less high-grade component in otherwise low-grade noninvasive bladder urothelial carcinoma, referred to as mixed-grade (MG) urothelial carcinoma, we reviewed all archival cases with such diagnosis between 2005 and 2014. Clinicopathological and outcome parameters were compared to those in our previously reported low- and high-grade noninvasive bladder urothelial carcinoma cohorts (LGUC and HGUC, respectively). The study included 31 MG urothelial carcinomas. Mean patient age was 67.6 years, and mean follow-up was 39.7 months. Intravesical treatment was administered in 15 patients (48.4%). Recurrence occurred in 14 cases (45.2%): 10 as LGUC and 4 as HGUC; there was no stage progression. Mean time to progression was 9 months (5-17 months), and there was no death of disease. MG urothelial carcinoma stage progression and dead of disease rates were comparable to that of LGUC. MG urothelial carcinoma stage progression was significantly lower than that of HGUC, P = .002, using Pearson χ(2) test. MG urothelial carcinoma patients with no intravesical treatment had higher incidence rate of grade progression (25%) compared to LGUC patients (7.9%); however, the difference was not statistically significant. MG urothelial carcinoma had a prognosis closer to "pure" LGUC than "pure" HGUC. Untreated MG urothelial carcinoma may have a higher rate of grade progression than LGUC, although more data are needed before this issue can be definitively addressed. Until such data are available, it is reasonable to keep MG urothelial carcinoma as a distinct grade category with potential management implications.

  10. Urinary Bladder Cancer: Biomarkers and Target Therapy, New Era for More Attention

    PubMed Central

    Mohammed, Amrallah A.; EL-Tanni, Hani; EL-Khatib, Hani M.; Mirza, Ahmad A.; Mirza, Abdulrahim A.; Alturaifi, Turki H.

    2016-01-01

    Currently, bladder cancer (BCa) evaluation depends mainly on traditional clinicopathological parameters encompassing tumor stage and grade, which will not reflect the behavior of the disease. Diverse molecular alterations are responsible for the heterogeneous course. The differences in molecular pathogenesis between non-invasive BCa and invasive BCa have been recognized. Molecular biomarkers are promising to predict progression and survival. The management of advanced BCa remains somewhat primitive in comparison with other more common malignancies. This topic will discuss the molecular pathways, biomarkers and potential targets that may improve the outcome in BCa. PMID:28058098

  11. Screening for Bladder and Other Urothelial Cancers

    MedlinePlus

    ... Events Scientific Meetings & Lectures Conferences Advisory Board Meetings Social Media Events Cancer Currents Blog All Press Releases 2017 ... Events Scientific Meetings & Lectures Conferences Advisory Board Meetings Social Media Cancer Currents Blog About NCI NCI Overview History ...

  12. Bladder cancer: a review of diagnosis and management.

    PubMed Central

    Metts, M. C.; Metts, J. C.; Milito, S. J.; Thomas, C. R.

    2000-01-01

    Bladder cancer is the fourth most commonly diagnosed malignancy in men and the eighth most common in women. It represents a spectrum of disease, ranging from superficial, well-differentiated disease, which does not significantly impact survival, to highly malignant tumors for which long term survival may be dismal. Transitional-cell carcinoma, which constitutes the vast majority of bladder cancers in the United States, may develop as carcinoma in situ or as invasive carcinoma. This article focuses on transitional-cell carcinoma with a review of the major aspects of the disease, including the epidemiology, diagnosis and staging, and management (including organ preservation). Therapeutic options are explored, including surgery, radiotherapy, chemotherapy, and combined modality therapy. PMID:10918764

  13. Surgical correction of bladder neck contracture following prostate cancer treatment.

    PubMed

    Bugeja, Simon; Andrich, Daniela E; Mundy, Anthony R

    2014-01-01

    The surgical and non-surgical treatment of localised prostate cancer may be complicated by bladder neck contractures, prostatic urethral stenoses and bulbomembranous urethral strictures. In general, such complications following radical prostatectomy are less extensive, easier to treat and associated with a better outcome and more rapid recovery than the same complications following radiotherapy, high-intensity focussed ultrasound and cryotherapy. Treatment options range from minimally invasive endoscopic procedures to more complex and specialised open surgical reconstruction.In this chapter the surgical management of bladder neck contractures following the treatment of prostate cancer is described together with the management of prostatic urethral stenoses and bulbomembranous urethral strictures, given the difficulty in distinguishing them from one another clinically.

  14. Patterns of Bladder Preservation Therapy Utilization for Muscle-Invasive Bladder Cancer.

    PubMed

    Rose, Tracy L; Deal, Allison M; Ladoire, Sylvain; Créhange, Gilles; Galsky, Matthew D; Rosenberg, Jonathan E; Bellmunt, Joaquim; Wimalasingham, Akhila; Wong, Yu-Ning; Harshman, Lauren C; Chowdhury, Simon; Niegisch, Guenter; Liontos, Michalis; Yu, Evan Y; Pal, Sumanta K; Chen, Ronald C; Wang, Andrew Z; Nielsen, Matthew E; Smith, Angela B; Milowsky, Matthew I

    2016-10-27

    Background: Trimodality bladder preservation therapy (BPT) in muscle invasive bladder cancer (MIBC) includes a maximal transurethral resection followed by concurrent chemoradiotherapy as an alternative to radical cystectomy (RC) in appropriately selected patients, or as a treatment option in non-cystectomy candidates. Several chemotherapy regimens can be used in BPT, but little is known about current practice patterns. Objective: To describe utilization patterns of BPT and associated survival outcomes in MIBC. Methods: Data were collected from the Retrospective International Study of Cancers of the Urothelial Tract (RISC), a database of 3,024 consecutive patients from 29 international academic centers from 2005 to 2013. Patients with clinical T2-T4aN0M0 urothelial cancer of the bladder were included. Results: 265 patients received BPT. Compared with the 1,447 patients who received RC, BPT patients were older, had poorer performance status, and had more comorbidities (p < 0.01 for all). Median overall survival (OS) was similar for patients treated with curative radiation doses in BPT and patients treated with RC (41 vs 46 months, p = 0.33, respectively). 45% of BPT patients received concurrent chemotherapy with radiation. The most common regimens included cisplatin alone (23%), carboplatin alone (22%), gemcitabine alone (10%), paclitaxel alone (9%), and 5-FU+mitomycin (5%). There were no significant differences in survival among chemotherapy regimens. Only 10 patients (4% of BPT patients) underwent salvage cystectomy. Conclusions: In clinical practice, BPT patients have similar survival to RC patients when treated with curative radiotherapy doses. Choice of concurrent chemotherapy regimen varied widely with no clear standard. Salvage cystectomy is rarely performed. Continued research is needed on the comparative effectiveness among BPT and RC, and among chemotherapy regimens in BPT.

  15. Patterns of Bladder Preservation Therapy Utilization for Muscle-Invasive Bladder Cancer

    PubMed Central

    Rose, Tracy L.; Deal, Allison M.; Ladoire, Sylvain; Créhange, Gilles; Galsky, Matthew D.; Rosenberg, Jonathan E.; Bellmunt, Joaquim; Wimalasingham, Akhila; Wong, Yu-Ning; Harshman, Lauren C.; Chowdhury, Simon; Niegisch, Guenter; Liontos, Michalis; Yu, Evan Y.; Pal, Sumanta K.; Chen, Ronald C.; Wang, Andrew Z.; Nielsen, Matthew E.; Smith, Angela B.; Milowsky, Matthew I.

    2016-01-01

    Background: Trimodality bladder preservation therapy (BPT) in muscle invasive bladder cancer (MIBC) includes a maximal transurethral resection followed by concurrent chemoradiotherapy as an alternative to radical cystectomy (RC) in appropriately selected patients, or as a treatment option in non-cystectomy candidates. Several chemotherapy regimens can be used in BPT, but little is known about current practice patterns. Objective: To describe utilization patterns of BPT and associated survival outcomes in MIBC. Methods: Data were collected from the Retrospective International Study of Cancers of the Urothelial Tract (RISC), a database of 3,024 consecutive patients from 29 international academic centers from 2005 to 2013. Patients with clinical T2-T4aN0M0 urothelial cancer of the bladder were included. Results: 265 patients received BPT. Compared with the 1,447 patients who received RC, BPT patients were older, had poorer performance status, and had more comorbidities (p < 0.01 for all). Median overall survival (OS) was similar for patients treated with curative radiation doses in BPT and patients treated with RC (41 vs 46 months, p = 0.33, respectively). 45% of BPT patients received concurrent chemotherapy with radiation. The most common regimens included cisplatin alone (23%), carboplatin alone (22%), gemcitabine alone (10%), paclitaxel alone (9%), and 5-FU+mitomycin (5%). There were no significant differences in survival among chemotherapy regimens. Only 10 patients (4% of BPT patients) underwent salvage cystectomy. Conclusions: In clinical practice, BPT patients have similar survival to RC patients when treated with curative radiotherapy doses. Choice of concurrent chemotherapy regimen varied widely with no clear standard. Salvage cystectomy is rarely performed. Continued research is needed on the comparative effectiveness among BPT and RC, and among chemotherapy regimens in BPT. PMID:28035321

  16. Arthritis and iritis after BCG therapy for bladder cancer.

    PubMed

    Price, G E

    1994-03-01

    A patient with preexisting inactive ankylosing spondylitis experienced a recurrence of back pain and his first episode of acute peripheral arthritis and iritis after a second course of treatment with BCG for bladder cancer. The occurrence of iritis after BCG therapy has not been reported. The recurrence of spondyloarthropathy and the new appearance of iritis may have been part of a generalized enhancement of immunological reactivity produced by the BCG.

  17. [Neoadjuvant or Adjuvant Chemotherapy for Bladder Cancer?].

    PubMed

    Hupe, M C; Kramer, M W; Kuczyk, M A; Merseburger, A S

    2015-05-01

    Advanced urothelial carcinoma of the bladder is associated with a high metastatic potential. Life expectancy for metastatic patients is poor and rarely exceeds more than one year without further therapy. Neoadjuvant chemotherapy can decrease the tumour burden while reducing the risk of death. Adjuvant chemotherapy has been discussed controversially. Patients with lymph node-positive metastases seem to benefit the most from adjuvant chemotherapy. In selected patients, metastasectomy can prolong survival. In metastastic patients, the combination of gemcitabine and cisplatin has become the new standard regimen due to a lower toxicity in comparison to the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). For second-line treatment, vinflunine is the only approved therapeutic agent.

  18. Pioglitazone use and the risk of bladder cancer.

    PubMed

    Kuo, Hsin-Wei; Tiao, Mao-Meng; Ho, Shu-Chen; Yang, Chun-Yuh

    2014-02-01

    This study aimed to identify the risk association between pioglitazone exposure and bladder cancer. A nested case-control study was performed using a representative database randomly sampled from National Health Insurance enrollees. The source cohort consisted of newly diagnosed diabetic patients from 1997 to 2009. Cases were identified as those with a diagnosis of bladder cancer from 2002 to 2009. For each case, four matched control individuals were randomly selected. A multiple logistic regression model was used to estimate the relative magnitude of risk in relation to the use of pioglitazone. In total, 259 cases and 1036 controls were identified. The prevalent use of pioglitazone is similar in cases and controls (adjusted odds ratio, 1.20; 95% confidence interval, 0.58-2.49). Compared to nonusers, these values were 1.08 (0.41-2.88) for those with cumulative pioglitazone use ≤ 8268 mg and 1.35 (0.48-3.79) for those with cumulative pioglitazone use > 8268 mg. This study does not provide support for the risk association between pioglitazone exposure and bladder cancer. Further confirmation is needed due to the limitation of small case number with relatively shorter exposure duration and lower cumulative dose.

  19. Neoadjuvant and adjuvant chemotherapy approaches for invasive bladder cancer.

    PubMed

    Raghavan, Derek; Burgess, Earle; Gaston, Kris E; Haake, Michael R; Riggs, Steven B

    2012-10-01

    Deeply invasive bladder cancer, representing approximately 20% of incident cases, is cured by radical cystectomy or radiotherapy in less than 50% of cases. In an effort to improve cure rates, based on objective response rates in metastatic disease of 40%-70% from combination chemotherapy regimens, systemic chemotherapy has been incorporated into programs of definitive treatment for this disease. Several randomized trials and a meta-analysis have confirmed a survival benefit from neoadjuvant chemotherapy followed by definitive local treatment, reflecting both median survival figures and cure rates. Despite several promising phase II trials, no randomized trial of classical adjuvant chemotherapy for bladder cancer has demonstrated an overall survival benefit, despite increments in disease-free survival. Molecular prognostication has been studied in an effort to improve the utility of systemic therapy for invasive non-metastatic bladder cancer, but randomized trials have not shown associated survival benefit. Despite level 1 evidence of a survival benefit from neoadjuvant MVAC (methotrexate, vinblastine, doxorubicin [Adriamycin], cisplatin) or cisplatin, methotrexate, and vinblastine (CMV) chemotherapy, more than 50% of incident cases do not receive such treatment.

  20. Immunotherapy of murine bladder cancer by irradiated tumor vaccine

    SciTech Connect

    Lamm, D.L.; Riggs, D.R.; DeHaven, J.I.; Bryner, R.W. )

    1991-01-01

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

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

    SciTech Connect

    Shipley, W.U.; Kaufman, S.D.; Prout, G.R. Jr.

    1987-10-01

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

  2. Mouse Models of Human Bladder Cancer as a Tool for Drug Discovery

    PubMed Central

    Seager, Catherine; Puzio-Kuter, Anna M.; Cordon-Cardo, Carlos; McKiernan, James; Abate-Shen, Cory

    2010-01-01

    Muscle-invasive bladder cancer is a deadly condition in dire need of effective new treatments. This unit contains a description of mouse models suitable for the evaluation of potential new therapies. Included is a genetically engineered mouse model of bladder cancer generated by the delivery of an adenovirus expressing Cre recombinase into the bladder lumen. Also described is an orthotopic mouse model created by the instillation of human bladder tumor cells into the bladder lumen of immune deficient mice. Protocols are also provided on the use of these models for the preclinical evaluation of new chemical entities, with mTOR inhibitors shown as an example. PMID:22294368

  3. Marker evaluation of human breast and bladder cancers

    SciTech Connect

    Mayall, B.H.; Carroll, P.R.; Chen, Ling-Chun; Cohen, M.B.; Goodson, W.H. III; Smith, H.S.; Waldman, F.M. )

    1990-11-02

    We are investigating multiple markers in human breast and bladder cancers. Our aim is to identify markers that are clinically relevant and that contribute to our understanding of the disease process in individual patients. Good markers accurately assess the malignant potential of a cancer in an individual patient. Thus, they help identify those cancers that will recur, and they may be used to predict more accurately time to recurrence, response to treatment, and overall prognosis. Therapy and patient management may then be optimized to the individual patient. Relevant markers reflect the underlying pathobiology of individual tumors. As a tissue undergoes transformation from benign to malignant, the cells lose their differentiated phenotype. As a generalization, the more the cellular phenotype, cellular proliferation and cellular genotype depart from normal, the more advanced is the tumor in its biological evolution and the more likely it is that the patient has a poor prognosis. We use three studies to illustrate our investigation of potential tumor markers. Breast cancers are labeled in vivo with 5-bromodeoxyuridine (BrdUrd) to give a direct measure of the tumor labeling index. Bladder cancers are analyzed immunocytochemically using an antibody against proliferation. Finally, the techniques of molecular genetics are used to detect allelic loss in breast cancers. 6 refs., 3 figs.

  4. Possible link of pioglitazone with bladder cancer in Japanese patients with type 2 diabetes.

    PubMed

    Fujimoto, Kanta; Hamamoto, Yoshiyuki; Honjo, Sachiko; Kawasaki, Yukiko; Mori, Kanako; Tatsuoka, Hisato; Matsuoka, Atsuko; Wada, Yoshiharu; Ikeda, Hiroki; Fujikawa, Jun; Koshiyama, Hiroyuki

    2013-02-01

    We retrospectively examined the frequency of bladder cancer in Japanese patients with type 2 diabetes in relation to use of pioglitazone. Among a total of 663 patients identified to be taking pioglitazone, 9 had bladder cancer (1.36%). Overall the hazard ratio of 1.75 [95% CI: 0.89-3.45] for pioglitazone for bladder cancer was not significant. However the prevalence of bladder cancer was 2.10% in patients taking pioglitazone for less than 24 months which was significant increased (HR 2.73 [95% CI: 1.11-6.72]).

  5. Cross-species analysis of the canine and human bladder cancer transcriptome and exome.

    PubMed

    Ramsey, Stephen A; Xu, Tanjin; Goodall, Cheri; Rhodes, Adelaide C; Kashyap, Amita; He, Jun; Bracha, Shay

    2017-04-01

    We investigated the correspondence between transcriptome and exome alterations in canine bladder cancer and the correspondence between these alterations and cancer-driving genes and transcriptional alterations in human bladder cancer. We profiled canine bladder tumors using mRNA-seq and exome-seq in order to investigate the similarity of transcriptional alterations in bladder cancer, in humans and canines, at the levels of gene functions, pathways, and cytogenetic regions. We found that the transcriptomes of canine and human bladder cancer are remarkably similar at the functional and pathway levels. We demonstrated that canine bladder cancer involves coordinated differential expression of genes within cytogenetic bands, and that these patterns are consistent with those seen in human bladder cancer. We found that genes that are mutated in canine bladder cancer are more likely to be transcriptionally downregulated than non-mutated genes, in the tumor. Finally we report three novel mutations (FAM133B, RAB3GAP2, and ANKRD52) for canine bladder cancer.

  6. Polymorphisms in the XRCC1 gene modify survival of bladder cancer patients treated with chemotherapy.

    PubMed

    Sacerdote, Carlotta; Guarrera, Simonetta; Ricceri, Fulvio; Pardini, Barbara; Polidoro, Silvia; Allione, Alessandra; Critelli, Rossana; Russo, Alessia; Andrew, Angeline S; Ye, Yuanqing; Wu, Xifeng; Kiemeney, Lambertus A; Bosio, Andrea; Casetta, Giovanni; Cucchiarale, Giuseppina; Destefanis, Paolo; Gontero, Paolo; Rolle, Luigi; Zitella, Andrea; Fontana, Dario; Vineis, Paolo; Matullo, Giuseppe

    2013-10-15

    Survival of bladder cancer patients depends on several factors including disease stage and grade at diagnosis, age, health status of the patient and the applied treatment. Several studies investigated the role of DNA repair genetic variants in cancer susceptibility, but only few studies investigated their role in survival and response to chemotherapy for bladder cancer. We genotyped 28 single nucleotide polymorphisms (SNP) in DNA repair genes in 456 bladder cancer patients, reconstructed haplotypes and calculated a score for combinations of the SNPs. We estimated Hazard Ratios (adjHR) for time to death. Among patients treated with chemotherapy, variant alleles of five SNPs in the XRCC1 gene conferred better survival (rs915927 adjHR 0.55 (95%CI 0.32-0.94); rs76507 adjHR 0.48 (95%CI 0.27-0.84); rs2854501 adjHR 0.25 (95%CI 0.12-0.52); rs2854509 adjHR 0.21 (95%CI 0.09-0.46); rs3213255 adjHR 0.46 (95%CI 0.26-0.80). In this group of patients, an increasing number of variant alleles in a XRCC1 gene score were associated with a better survival (26% decrease of risk of death for each additional variant allele in XRCC1). By functional analyses we demonstrated that the previous XRCC1 SNPs confer lower DNA repair capacity. This may support the hypothesis that survival in these patients may be modulated by the different DNA repair capacity determined by genetic variants. Chemotherapy treated cancer patients bearing an increasing number of "risky" alleles in XRCC1 gene had a better survival, suggesting that a proficient DNA repair may result in resistance to therapy and shorter survival. This finding may have clinical implications for the choice of therapy.

  7. miR-613 inhibits bladder cancer proliferation and migration through targeting SphK1

    PubMed Central

    Yu, Haifeng; Duan, Ping; Zhu, Haibo; Rao, Dapang

    2017-01-01

    Objectives: Increasing evidence has suggested that microRNA (miRNA) dysregulation may contribute to tumor progression and metastasis. However, the role of miR-613 in bladder cancer was still unknown. Materials and methods: qRT-PCR and Western blotting were performed to detect the expression of miR-613 and its direct target gene. CCK-8 analysis, qRT-PCR and cell invasion were performed to measure the cell function. Results: We demonstrated that the expression of miR-613 was downregulated in the bladder cancer cell lines. In addition, miR-613 expression was downregulated in the bladder cancer tissues compared to the adjacent normal tissues. Out of 35 bladder cancer tissues, miR-613 was downregulated in 27 cases compared to the adjacent tissues. Ectopic expression of miR-613 suppressed the bladder cancer cell proliferation and invasion. Moreover, miR-613 overexpression enhanced the expression of epithelial biomarker, Ecadherin, and suppressed the expression of mesenchymal biomarker, Vimentin, Snail and N-cadherin. Furthermore, we identified the Sphingosine kinase 1 (SphK1) as the direct target gene of miR-613 in the bladder cancer cell. Restoration of Sphk1 partially rescued miR-613-inhibited bladder cancer cell proliferation, invasion and EMT. Conclusions: These data suggested that miR-613 acted a tumor suppressive role in bladder cancer through targeting SphK1 in bladder. PMID:28386347

  8. Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance

    PubMed Central

    Kurtova, Antonina V.; Xiao, Jing; Mo, Qianxing; Pazhanisamy, Senthil; Krasnow, Ross; Lerner, Seth P.; Chen, Fengju; Roh, Terrence T.; Lay, Erica; Ho, Philip Levy; Chan, Keith Syson

    2015-01-01

    Cytotoxic chemotherapy is effective in debulking tumour masses initially; however, in some patients tumours become progressively unresponsive after multiple treatment cycles. Previous studies have demonstrated that cancer stem cells (CSCs) are selectively enriched after chemotherapy through enhanced survival1–3. Here we reveal a new mechanism by which bladder CSCs actively contribute to therapeutic resistance via an unexpected proliferative response to re-populate residual tumours between chemotherapy cycles, using human bladder cancer xenografts. Further analyses demonstrate the recruitment of a quiescent label-retaining pool of CSCs into cell division in response to chemotherapy-induced damages, similar to mobilization of normal stem cells during wound repair4–7. While chemotherapy effectively induces apoptosis, associated prostaglandin E2 (PGE2) release paradoxically promotes neighbouring CSC repopulation. This repopulation can be abrogated by a PGE2-neutralizing antibody and celecoxib drug-mediated blockade of PGE2 signalling. In vivo administration of the cyclooxygenase-2 (COX2) inhibitor celecoxib effectively abolishes a PGE2- and COX2-mediated wound response gene signature, and attenuates progressive manifestation of chemoresistance in xenograft tumours, including primary xenografts derived from a patient who was resistant to chemotherapy. Collectively, these findings uncover a new underlying mechanism that models the progressive development of clinical chemoresistance, and implicate an adjunctive therapy to enhance chemotherapeutic response of bladder urothelial carcinomas by abrogating early tumour repopulation. PMID:25470039

  9. Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance.

    PubMed

    Kurtova, Antonina V; Xiao, Jing; Mo, Qianxing; Pazhanisamy, Senthil; Krasnow, Ross; Lerner, Seth P; Chen, Fengju; Roh, Terrence T; Lay, Erica; Ho, Philip Levy; Chan, Keith Syson

    2015-01-08

    Cytotoxic chemotherapy is effective in debulking tumour masses initially; however, in some patients tumours become progressively unresponsive after multiple treatment cycles. Previous studies have demonstrated that cancer stem cells (CSCs) are selectively enriched after chemotherapy through enhanced survival. Here we reveal a new mechanism by which bladder CSCs actively contribute to therapeutic resistance via an unexpected proliferative response to repopulate residual tumours between chemotherapy cycles, using human bladder cancer xenografts. Further analyses demonstrate the recruitment of a quiescent label-retaining pool of CSCs into cell division in response to chemotherapy-induced damages, similar to mobilization of normal stem cells during wound repair. While chemotherapy effectively induces apoptosis, associated prostaglandin E2 (PGE2) release paradoxically promotes neighbouring CSC repopulation. This repopulation can be abrogated by a PGE2-neutralizing antibody and celecoxib drug-mediated blockade of PGE2 signalling. In vivo administration of the cyclooxygenase-2 (COX2) inhibitor celecoxib effectively abolishes a PGE2- and COX2-mediated wound response gene signature, and attenuates progressive manifestation of chemoresistance in xenograft tumours, including primary xenografts derived from a patient who was resistant to chemotherapy. Collectively, these findings uncover a new underlying mechanism that models the progressive development of clinical chemoresistance, and implicate an adjunctive therapy to enhance chemotherapeutic response of bladder urothelial carcinomas by abrogating early tumour repopulation.

  10. Bladder cancer diagnosis from bladder wash by Fourier transform infrared spectroscopy as a novel test for tumor recurrence.

    PubMed

    Gok, Seher; Aydin, Ozge Z; Sural, Yavuz S; Zorlu, Ferruh; Bayol, Umit; Severcan, Feride

    2016-09-01

    This study proposes Fourier Transform Infrared (FTIR) spectroscopy as a more sensitive, rapid, non-destructive and operator-independent analytical diagnostic method for bladder cancer recurrence from bladder wash than other routinely used urine cytology and cystoscopy methods. A total of 136 patients were recruited. FTIR spectroscopic experiments were carried out as a blind study, the classification results of which were then compared with those of cytology and cystoscopy. Firstly, 71 samples (n = 37; bladder cancer and n = 34; control) were studied with transmittance FTIR spectroscopy. After achieving successful differentiation of the groups, to develop a more rapid diagnostic tool and check the reproducibility of the results, the work was continued with different samples (n = 65 as n = 44; bladder cancer and n = 21; control), using the reflection mode (ATR) of FTIR spectroscopy by a different operator. The results revealed significant alterations in moleculer content in the cancer group. Based on the spectral differences, using transmittance FTIR spectroscopy coupled with chemometrics, the diseased group was successfully differentiated from the control. When only carcinoma group was taken into consideration a sensitivity value of 100% was achieved. Similar results were also obtained by ATR-FTIR spectroscopy. This study shows the power of infrared spectroscopy in the diagnosis of bladder cancer.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

    Makarević, Jasmina; Rutz, Jochen; Juengel, Eva; Kaulfuss, Silke; Tsaur, Igor; Nelson, Karen; Pfitzenmaier, Jesco

    2014-01-01

    The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml) was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as well as tumor cell migration was examined. Effects of drug treatment on integrin α and β subtypes, on integrin-linked kinase (ILK) and total and activated focal adhesion kinase (FAK) were also determined. Integrin knock-down was carried out to evaluate integrin influence on migration and adhesion. A 24 h or 2 week amygdalin application distinctly reduced tumor cell adhesion and migration of UMUC-3 and RT112 cells. TCCSUP adhesion was also reduced, but migration was elevated under amygdalin. Integrin subtype expression was significantly and specifically altered by amygdalin depending on the cell line. ILK was moderately, and activated FAK strongly, lost in all tumor cell lines in the presence of amygdalin. Knock down of β1 integrin caused a significant decrease in both adhesion and migration of UMUC-3 cells, but a significant increase in TCCSUP adhesion. Knock down of β4 integrin caused a significant decrease in migration of RT112 cells. Since the different actions of amygdalin on the different cell lines was mirrored by β1 or β4 knock down, it is postulated that amygdalin influences adhesion and migratory properties of bladder cancer cells by modulating β1 or β4 integrin expression. The amygdalin induced increase in TCCSUP migratory behavior indicates that any anti-tumor benefits from amygdalin (seen with the other two cell lines) may depend upon the cancer cell type. PMID:25333694

  13. Matrix-dependent Plasticity of the Malignant Phenotype of Bladder Cancer Cells

    PubMed Central

    Hurst, Robert E.; Kyker, Kimberly D.; Bonner, Rebecca B.; Bowditch, Ron D.; Hemstreet, George P.

    2008-01-01

    The purpose of this study was to investigate the effect of cancer- and normal basement membrane-derived extracellular matrix to modulate the phenotype of bladder cancer cell lines. Five lines, varying in malignancy from papilloma to highly undifferentiated and invasive and immortalized human urothelial cells, were grown on two extracellular matrix preparations, Matrigel and SISgel. Matrigel represents matrix remodeled by malignancy while SISgel, obtained from small intestine submucosa (SIS), represents the normal matrix supporting differentiated cell growth. On Matrigel, regardless of the content of growth factors, the invasive lines displayed an invasive phenotype, while the low grade lines grew as papillary structures. In contrast, when the same cells were grown on SISgel, they grew as a layer of cells one to 5 cells thick, failed to invade, and expressed cell-surface E-cadherin. Unlike breast cancer cells, neutralization of β1, β4 and α6 integrins altered cell-cell and cell-matrix adhesiveness but did not alter the phenotype. When invasive cells were grown on mixtures of SISgel and Matrigel, the phenotype changed gradually, not abruptly, indicating that factors within the gel reversibly alter the phenotypic expression of invasion. In summary, the phenotype of bladder cancer cells growing in tissue-like 3-dimensional culture is highly plastic, and malignant properties such as invasion and papillary growth can be suppressed by the matrix. PMID:12926044

  14. [Morphological results of repeated transurethral resection of the bladder for muscle-non-invasive cancer].

    PubMed

    Seregin, I V; Seregin, A V; Dadashev, É O; Polozhentsev, O B; Loran, O B

    2013-01-01

    Operating material taken from 101 patients aged 32 to 88 years with verified bladder cancer was investigated. Repeated morphological analysis of biopsy material obtained after repeated transurethral resection (TUR) has revealed 35.6% of residual tumors, and the same stage cancer was diagnosed in 23% of cases, lower stage Ta cancer--in 5% of cases. Underestimating the stage took place in 7.9% of cases. Residual tumors according to histological examination were revealed in 24.7% of patients. In tumor size larger than 3 cm, the frequency of detection of residual tumors and muscular invasion was 44.8 and 12.1%, and in tumor size less than 3 cm--23.2 and 2.3%, respectively. Residual tumor was found in 45.7% of cases with rT1G3 and in 27.2% of cases with rT1G2. The muscle invasion was observed only in low-grade tumors--13.5% of cases. In the presence of muscular tissue, invasion was diagnosed in 1.4% of cases, and in the absence of muscular tissue--in 20.5%. Repeated TUR of bladder for muscles-non-invasive cancer allows achieving optimal local control, obtaining additional histological material for morphological examination to confirm the stage of the disease, there from, choose the appropriate treatment and remove residual tumor.

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

    PubMed

    Cazier, J-B; Rao, S R; McLean, C M; Walker, A K; Walker, A L; Wright, B J; Jaeger, E E M; Kartsonaki, C; Marsden, L; Yau, C; Camps, C; Kaisaki, P; Taylor, J; Catto, J W; Tomlinson, I P M; Kiltie, A E; Hamdy, F C

    2014-04-29

    Bladder cancers are a leading cause of death from malignancy. Molecular markers might predict disease progression and behaviour more accurately than the available prognostic factors. Here we use whole-genome sequencing to identify somatic mutations and chromosomal changes in 14 bladder cancers of different grades and stages. As well as detecting the known bladder cancer driver mutations, we report the identification of recurrent protein-inactivating mutations in CDKN1A and FAT1. The former are not mutually exclusive with TP53 mutations or MDM2 amplification, showing that CDKN1A dysfunction is not simply an alternative mechanism for p53 pathway inactivation. We find strong positive associations between higher tumour stage/grade and greater clonal diversity, the number of somatic mutations and the burden of copy number changes. In principle, the identification of sub-clones with greater diversity and/or mutation burden within early-stage or low-grade tumours could identify lesions with a high risk of invasive progression.

  16. Apoptotic effect of the selective PPARβ/δ agonist GW501516 in invasive bladder cancer cells.

    PubMed

    Péchery, Adeline; Fauconnet, Sylvie; Bittard, Hugues; Lascombe, Isabelle

    2016-11-01

    GW501516 is a selective and high-affinity synthetic agonist of peroxisome proliferator-activated receptor β/δ (PPARβ/δ). This molecule promoted the inhibition of proliferation and apoptosis in few cancer cell lines, but its anticancer action has never been investigated in bladder tumor cells. Thus, this study was undertaken to determine whether GW501516 had antiproliferative and/or apoptotic effects on RT4 and T24 urothelial cancer cells and to explore the molecular mechanisms involved. Our results indicated that, in RT4 cells (derived from a low-grade papillary tumor), GW501516 did not induce cell death. On the other hand, in T24 cells (derived from an undifferentiated high-grade carcinoma), this PPARβ/δ agonist induced cytotoxic effects including cell morphological changes, a decrease of cell viability, a G2/M cell cycle arrest, and the cell death as evidenced by the increase of the sub-G1 cell population. Furthermore, GW501516 triggered T24 cell apoptosis in a caspase-dependent manner including both extrinsic and intrinsic apoptotic pathways through Bid cleavage. In addition, the drug led to an increase of the Bax/Bcl-2 ratio, a mitochondrial dysfunction associated with the dissipation of ΔΨm, and the release of cytochrome c from the mitochondria to the cytosol. GW501516 induced also ROS generation which was not responsible for T24 cell death since NAC did not rescue cells upon PPARβ/δ agonist exposure. For the first time, our data highlight the capacity of GW501516 to induce apoptosis in invasive bladder cancer cells. This molecule could be relevant as a therapeutic drug for high-grade urothelial cancers.

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

    PubMed

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

    2013-01-01

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

  18. Complete Response and Fatigue Improvement With the Combined Use of Cyclophosphamide and Quercetin in a Patient With Metastatic Bladder Cancer

    PubMed Central

    Di Lorenzo, Giuseppe; Pagliuca, Martina; Perillo, Teresa; Zarrella, Aquilino; Verde, Antonio; De Placido, Sabino; Buonerba, Carlo

    2016-01-01

    Abstract Bladder cancer is a major cause of cancer-related mortality, with an estimated 74,000 new cases and 16,000 deaths in the United States in 2015. In patients with metastatic disease, vinflunine and taxanes are the most widely used chemotherapy agents in the second-line setting after failure of platinum-based treatment. Cyclophosphamide has been used in combination with paclitaxel in urothelial carcinoma of the bladder, but there are no data about the effectiveness of cyclophosphamide administered as a single agent. We here describe the first case of an advanced bladder cancer patient suffering from grade 2 fatigue. He benefited from administration of third-line single-agent metronomic oral cyclophosphamide plus oral doses of quercetin. A complete, prolonged radiologic response according to the RECIST criteria 1.1 was achieved with minimal toxicity and an improvement in fatigue. Further studies are required to assess the potential benefits associated with the combined use of cyclophosphamide plus quercetin in advanced bladder cancer patients. PMID:26844468

  19. Metabolomic profiling reveals potential markers and bioprocesses altered in bladder cancer progression.

    PubMed

    Putluri, Nagireddy; Shojaie, Ali; Vasu, Vihas T; Vareed, Shaiju K; Nalluri, Srilatha; Putluri, Vasanta; Thangjam, Gagan Singh; Panzitt, Katrin; Tallman, Christopher T; Butler, Charles; Sana, Theodore R; Fischer, Steven M; Sica, Gabriel; Brat, Daniel J; Shi, Huidong; Palapattu, Ganesh S; Lotan, Yair; Weizer, Alon Z; Terris, Martha K; Shariat, Shahrokh F; Michailidis, George; Sreekumar, Arun

    2011-12-15

    Although alterations in xenobiotic metabolism are considered causal in the development of bladder cancer, the precise mechanisms involved are poorly understood. In this study, we used high-throughput mass spectrometry to measure over 2,000 compounds in 58 clinical specimens, identifying 35 metabolites which exhibited significant changes in bladder cancer. This metabolic signature distinguished both normal and benign bladder from bladder cancer. Exploratory analyses of this metabolomic signature in urine showed promise in distinguishing bladder cancer from controls and also nonmuscle from muscle-invasive bladder cancer. Subsequent enrichment-based bioprocess mapping revealed alterations in phase I/II metabolism and suggested a possible role for DNA methylation in perturbing xenobiotic metabolism in bladder cancer. In particular, we validated tumor-associated hypermethylation in the cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) promoters of bladder cancer tissues by bisulfite sequence analysis and methylation-specific PCR and also by in vitro treatment of T-24 bladder cancer cell line with the DNA demethylating agent 5-aza-2'-deoxycytidine. Furthermore, we showed that expression of CYP1A1 and CYP1B1 was reduced significantly in an independent cohort of bladder cancer specimens compared with matched benign adjacent tissues. In summary, our findings identified candidate diagnostic and prognostic markers and highlighted mechanisms associated with the silencing of xenobiotic metabolism. The metabolomic signature we describe offers potential as a urinary biomarker for early detection and staging of bladder cancer, highlighting the utility of evaluating metabolomic profiles of cancer to gain insights into bioprocesses perturbed during tumor development and progression.

  20. Bladder Cancer Screening in Lebanese Population: There is Nothing more Unequal than the Equal Treatment of Unequal People.

    PubMed

    Shahait, Mohammed; Bulbul, Muhammad

    2016-10-27

    Bladder cancer screening has been perplexing the uro-oncological community for the last decade. In this commentary, we ruminate on the feasibility of bladder cancer screening in our population based on epidemiological proponents.

  1. Stat3 Activation in Urothelial Stem Cells Leads to Direct Progression to Invasive Bladder Cancer

    PubMed Central

    Ho, Philip Levy; Lay, Erica Julianne; Jian, Weiguo; Parra, Diana; Chan, Keith Syson

    2012-01-01

    Two subtypes of human bladder cancer, noninvasive papillary and muscle-invasive cancer, develop through independent pathologic and molecular pathways. Human invasive bladder cancer frequently develops without prior clinical evidence of a noninvasive tumor stage. However, an animal model that recapitulates this unique clinical progression of invasive bladder cancer has not yet been developed. In this study, we created a novel transgenic mouse model of invasive bladder cancer by targeting an active dimerized form of Stat3 to the basal cells of bladder epithelium. When exposed to the carcinogen nitrosamine, Stat3-transgenic mice developed invasive cancer directly from carcinoma in situ (CIS), bypassing the noninvasive papillary tumor stage. Remarkably, invasive bladder cancer driven by active Stat3 was predominantly composed of stem cells, which were characterized by cytokeratin 14 (CK14) staining and enhanced tumor sphere-forming ability. Active Stat3 was also shown to localize to the nucleus of human invasive bladder cancers that were primarily composed of CK14+ stem cells. Together, our findings show that Stat3-induced stem cell expansion plays a critical role in the unique clinical progression of invasive bladder cancer through the CIS pathway. PMID:22532166

  2. Expression of Aggrus/podoplanin in bladder cancer and its role in pulmonary metastasis

    PubMed Central

    Takagi, Satoshi; Oh-hara, Tomoko; Sato, Shigeo; Gong, Bo; Takami, Miho; Fujita, Naoya

    2014-01-01

    Platelet aggregation-inducing factor Aggrus, also known as podoplanin, is associated with tumor malignancy by promoting hematogenous metastasis. Aggrus overexpression has been reported in some tumor tissues including lung, esophagus, head and neck and brain. We here found the frequent upregulation of aggrus mRNA in urinary bladder cancers using cancer tissue panels from various organs. Immunohistochemical analysis confirmed Aggrus protein expression in urinary bladder cancers and suggested a positive correlation between Aggrus expression and metastatic tendency in bladder cancers. Endogenous expression of Aggrus protein on the cell surface was found in the mouse bladder cancer MBT-2 cell line and human bladder cancer SCaBER cell lines. Knockdown of Aggrus expression in MBT-2 cells decreased their ability to induce platelet aggregation and form pulmonary metastasis in syngeneic mouse models. Knockdown of Aggrus expression in the human bladder cancer SCaBER cells also attenuated their ability to induce platelet aggregation and form pulmonary metastasis in mice. Moreover, pulmonary metastasis of SCaBER cells was prevented by prior administration of our generated anti-Aggrus neutralizing monoclonal antibodies by attenuating their retention in lung. These results indicate that Aggrus plays an important role in bladder cancer metastasis. Thus, anti-Aggrus neutralizing antibodies would be useful for the prevention of hematogenous metastasis of Aggrus-positive bladder cancer. PMID:24222607

  3. [The role of low-field strength magnetic resonance imaging in bladder cancer staging].

    PubMed

    Lutsenko, P E; Bulanova, T V; Chernyshev, I V; Churaiants, V V

    2007-01-01

    This article shows the role of magnetic resonance imaging (MRI) in complex diagnostics of urinary bladder cancer. The paper analyzes the authors' own data of urinary bladder MRI in 40 patients with histologically proven bladder cancer. This study demonstrates the additional capacities of low-field strength MRI with enhanced technique including conventional T1-, T2-weighted images along with FLAIR and PD images.

  4. Carbon-ion radiotherapy for locally advanced cervical cancer with bladder invasion

    PubMed Central

    Shiba, Shintaro; Wakatsuki, Masaru; Kato, Shingo; Ohno, Tatsuya; Okonogi, Noriyuki; Karasawa, Kumiko; Kiyohara, Hiroki; Tsujii, Hirohiko; Nakano, Takashi; Kamada, Tadashi; Shozu, Makio

    2016-01-01

    The purpose of this study was to evaluate the efficacy and toxicities of carbon-ion radiotherapy (C-ion RT) for locally advanced cervical cancer with bladder invasion by a subset analysis of pooled data from eight prospective clinical trials at the National Institute of Radiological Sciences. Between June 1995 and January 2014, 29 patients with locally advanced cervical cancer with bladder invasion were identified. The median age was 56 years old (range 31–79 years old). The median tumor size at diagnosis on magnetic resonance imaging was 6.7 cm (range 3.5–11.0 cm). Histologically, 20 patients had squamous cell carcinoma and 9 had adenocarcinoma. C-ion RT was performed as a dose-escalation study in the initial trials. All patients received prophylactic whole-pelvic or extended-field irradiation and local boost. The total dose to the cervical tumor was 52.8–74.4 Gy (relative biological effectiveness) in 20 or 24 fractions. Weekly cisplatin (40 mg/m2/week, five cycles) was concurrently given to four patients. The median follow-up of all patients was 28.6 months (range 8.8–238.6 months). Grade 2 or higher late complications in the bladder were observed in eight patients, with seven developing vesicovaginal fistula. Six patients had Grade 2 or higher complications in the rectosigmoid colon. The 3-year overall survival rate was 47%, the 3-year local control rate was 66%, and the 3-year disease-free survival rate was 28%. In this study, C-ion RT showed favorable local control with reasonable toxicities, but the results were still unsatisfactory. We have the expectation of improvement of therapeutic effects by using C-ion RT with concurrent chemotherapy. PMID:27422932

  5. MiR-122 targets VEGFC in bladder cancer to inhibit tumor growth and angiogenesis

    PubMed Central

    Wang, Yi; Xing, Qing-Fei; Liu, Xiao-Qiang; Guo, Zhan-Jun; Li, Chang-Ying; Sun, Guang

    2016-01-01

    Previous studies indicate that microRNA-122 (miR-122) is down-regulated in several cancer cells and regulates cell apoptosis, proliferation, metastasis, and tumor angiogenesis. However, the mount of miR-122 in bladder cancer and the pivotal molecular mechanisms of miR-122 used to regulate bladder carcinogenesis and angiogenesis remain to be clarified. Here, we reveal that miR-122 expression is down-regulated in human bladder cancer tissues and cell lines. MiR-122 represses vascular endothelial growth factor C (VEGFC) post-transcriptional expression by directly binding to its 3’-UTR. The protein kinase B (AKT) and mammalian target of rapamycin (mTOR), which are the most important downstream molecules of VEGFC, are also decreased in bladder cancer cell after miR-122 overexpression. Furthermore, miR-122 over-expression decreases bladder cancer cell migration, invasion, colony formation in vitro and slow bladder cancer growth and angiogenesis in vivo. Finally, miR-122 sensitizes bladder cancer cells to cisplatin-induced apoptosis. Taken together, these studies suggest that miR-122 serves as a tumor suppressor and down-regulating VEGFC expression, leading to the inhibition of bladder cancer growth and angiogenesis. PMID:27508026

  6. The role of the androgen receptor in the development and progression of bladder cancer.

    PubMed

    Li, Yi; Izumi, Koji; Miyamoto, Hiroshi

    2012-07-01

    Men are at a higher risk of developing bladder cancer than women. Since bladder cancer cell lines and tissues were found to express the androgen receptor, efforts have been made to inspect whether androgen-mediated androgen receptor signals are implicated in bladder carcinogenesis as well as cancer progression. Mounting evidence supports the view that bladder cancer is a member of the endocrine-related tumors and may clearly explain the gender-specific difference in the incidence. However, the underlying mechanisms of how androgen receptor signals regulate bladder cancer growth are still far from fully characterized. Moreover, it remains controversial whether the androgen receptor pathway always plays a dominant role in bladder cancer progression. In this review, we summarize the available data on the involvement of androgen receptor signaling in bladder cancer. In particular, current evidence demonstrating the stimulatory effects of androgens on tumor progression or, more convincingly, tumorigenesis via the androgen receptor pathway may offer great potential for androgen deprivation as a therapeutic or chemopreventive option in patients with bladder cancer.

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

    EPA Science Inventory

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

  8. Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2

    SciTech Connect

    Ho, Melissa E.; Quek, Sue -Ing; True, Lawrence D.; Seiler, Roland; Fleischmann, Achim; Bagryanova, Lora; Kim, Sara R.; Chia, David; Goodglick, Lee; Shimizu, Yoshiko; Rosser, Charles J.; Gao, Yuqian; Liu, Alvin Y.

    2016-02-15

    Anterior gradient 2 (AGR2) is a cancer-associated secreted protein found predominantly in adenocarcinomas. Given its ubiquity in solid tumors, cancer-secreted AGR2 could be a useful biomarker in urine or blood for early detection. Normal organs express AGR2 and might also secrete AGR2, which would impact on the utility of AGR2 as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is, however, secreted by the urothelial cells as no measurable amounts could be detected in urine. The urinary proteomes of healthy people contain no listing for AGR2. The blood proteomes also contain no significant peptide counts for AGR2 suggesting that little urothelial secretion into capillaries of the lamina propria. Expression is lost in urothelial carcinoma, but 25% primary tumors retained AGR2 expression in a cohort of lymph node positive cases. AGR2 is secreted by the urothelial carcinoma cells as urinary AGR2 was measured in the voided urine of 25% of the cases analyzed in a cohort of cancer vs. non-cancer urine, which matched the frequency of AGR2-positive urothelial carcinoma. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. In addition to secretion, AGR2 is also localized to the cell surface. Thus, secretion/cell surface localization of AGR2 is pecific to cancer while expression itself is not. Lastly, since AGR2 is found in many solid tumor types, this tumor-associated antigen constitutes a highly promising therapeutic target.

  9. Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2

    DOE PAGES

    Ho, Melissa E.; Quek, Sue -Ing; True, Lawrence D.; ...

    2016-02-15

    Anterior gradient 2 (AGR2) is a cancer-associated secreted protein found predominantly in adenocarcinomas. Given its ubiquity in solid tumors, cancer-secreted AGR2 could be a useful biomarker in urine or blood for early detection. Normal organs express AGR2 and might also secrete AGR2, which would impact on the utility of AGR2 as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is, however, secreted by the urothelial cells as no measurable amounts could be detected in urine. The urinary proteomes of healthy people contain no listing for AGR2. The blood proteomes also contain no significantmore » peptide counts for AGR2 suggesting that little urothelial secretion into capillaries of the lamina propria. Expression is lost in urothelial carcinoma, but 25% primary tumors retained AGR2 expression in a cohort of lymph node positive cases. AGR2 is secreted by the urothelial carcinoma cells as urinary AGR2 was measured in the voided urine of 25% of the cases analyzed in a cohort of cancer vs. non-cancer urine, which matched the frequency of AGR2-positive urothelial carcinoma. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. In addition to secretion, AGR2 is also localized to the cell surface. Thus, secretion/cell surface localization of AGR2 is pecific to cancer while expression itself is not. Lastly, since AGR2 is found in many solid tumor types, this tumor-associated antigen constitutes a highly promising therapeutic target.« less

  10. Molecular genetics and genomics progress in urothelial bladder cancer.

    PubMed

    Netto, George J

    2013-11-01

    The clinical management of solid tumor patients has recently undergone a paradigm shift as the result of the accelerated advances in cancer genetics and genomics. Molecular diagnostics is now an integral part of routine clinical management in lung, colon, and breast cancer patients. In a disappointing contrast, molecular biomarkers remain largely excluded from current management algorithms of urologic malignancies. The need for new treatment alternatives and validated prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management is pressing. Identifying robust predictive biomarkers that can stratify response to newly introduced targeted therapeutics is another crucially needed development. The following is a brief discussion of some promising candidate biomarkers that may soon become a part of clinical management of bladder cancers.

  11. Constitutional and occupational risk factors associated with bladder cancer

    PubMed Central

    Ferrís, J.; Garcia, J.; Berbel, O.; Ortega, J.A.

    2016-01-01

    Objective Bladder carcinoma (BC) is the fourth most common type of cancer in males from Western countries, with primary prevention an important healthcare challenge. We review the associated constitutional and occupational risk factors (RF), with greater or lesser scientific evidence, in the etiology of BC. Material and methods Literature review of the last 25 years of the constitutional and occupational RF associated with BC, conducted on MedLine, CancerLit, Science Citation Index and Embase. The search profiles were Risk factors/Genetic factors/Genetic polymorphisms/Epidemiology/Occupational factors and Bladder cancer. Results The main RF were (a) age and gender (diagnosed at age 65 and over, with a 4:1 ratio of males to females); (b) race, ethnicity and geographic location (predominantly in Caucasians and in Southern European countries); (c) genetic (N-acetyltransferase-2 and glutathione s-transferase M1 gene mutations, which significantly increase the risk for BC); (d) occupational, which represent 5–10% of BC RF; and (f) occupations with high BC risk, such as aluminum production, the manufacture of dyes, paints and colourings, the rubber industry and the extraction and industrial use of fossil fuels. Conclusions BC is the end result of the variable combination of constitutional and environmental RF, the majority of which are unknown. The most significant constitutional RF are related to age, gender, race, ethnicity geographic location and genetic polymorphisms. The main occupational RF are those related to aromatic amines and polycyclic aromatic hydrocarbons. PMID:23664103

  12. Developing urinary metabolomic signatures as early bladder cancer diagnostic markers.

    PubMed

    Shen, Chong; Sun, Zeyu; Chen, Deying; Su, Xiaoling; Jiang, Jing; Li, Gonghui; Lin, Biaoyang; Yan, Jiajun

    2015-01-01

    Early detection is vital to improve the overall survival rate of bladder cancer (BCa) patients, yet there is a lack of a reliable urine-based assay for early detection of BCa. Urine metabolites represented a potential rich source of biomarkers for BCa. This study aimed to develop a metabolomics approach for high coverage discovery and identification of metabolites in urine samples. Urine samples from 23 early stage BCa patients and 21 healthy volunteers with minimum sample preparations were analyzed by a short 30 min UPLC-HRMS method. We detected and quantified over 9000 unique UPLC-HRMS features, which is more than four times than about 2000 features detected in previous urine metabolomic studies. Furthermore, multivariate OPLS-DA classification models were established to differentiate urine samples from bladder cancer cohort and normal health cohort. We identified three BCa-upregulated metabolites: nicotinuric acid, trehalose, AspAspGlyTrp, and three BCa-downregulated metabolites: inosinic acid, ureidosuccinic acid, GlyCysAlaLys. Finally, analysis of six post-surgery BCa urine samples showed that these BCa-metabolomic features reverted to normal state after tumor removal, suggesting that they reflected metabolomic features associated with BCa. ROC analyses using two linear regression models to combine the identified markers showed a high diagnostic performance for detecting BCa with AUC (area under the ROC curve) values of 0.919 to 0.934. In summary, we developed a high coverage metabolomic approach that has potential for biomarker discovery in cancers.

  13. Systemic management of bladder cancer in Egypt: revisited.

    PubMed

    Khaled, Hussein M

    2005-09-01

    Bladder cancer is still the most frequent malignant tumor among Egyptian males. It has a peculiar biologic, clinico-pathologic features and responsiveness to chemotherapy profile than that observed in Western countries. The current review aims to demonstrate the present state-of- art in using systemic therapy as part of the management options available to treat such patients at different stages of their disease. Individualizing therapy for these patients based on more rationale basis is the challenge that oncologists must face in the near future.

  14. MiR-4295 promotes cell growth in bladder cancer by targeting BTG1

    PubMed Central

    Nan, Yong-Hao; Wang, Jun; Wang, Yao; Sun, Peng-Hao; Han, Yu-Ping; Fan, Li; Wang, Kai-Chen; Shen, Fu-Jun; Wang, Wei-Hua

    2016-01-01

    microRNAs (miRNAs) have been demonstrated to contribute to tumor progression and metastasis, and have been proposed to be key regulators of diverse biological processes. In this study, we report that miR-4295 is deregulated in bladder cancer tissues and cell lines. To characterize the role of miR-4295 in bladder cancer cells, we performed functional assays. The overexpression of miR-4295 significantly promoted bladder cancer cell proliferation, colony formation, and migration. Moreover, its downregulation induced cell cycle arrest and apoptosis of bladder cancer cells. Furthermore, a luciferase reporter assay and rescue experiment indicated that miR-4295 directly targets BTG1 by binding its 3’UTR. In conclusion, these results demonstrate that miR-4295 acts as an oncogene and may be a potential biomarker for bladder cancer diagnosis and treatment. PMID:27904689

  15. Collaborating to Move Research Forward: Proceedings of the 10th Annual Bladder Cancer Think Tank

    PubMed Central

    Kamat, Ashish M.; Agarwal, Piyush; Bivalacqua, Trinity; Chisolm, Stephanie; Daneshmand, Sia; Doroshow, James H.; Efstathiou, Jason A.; Galsky, Matthew; Iyer, Gopa; Kassouf, Wassim; Shah, Jay; Taylor, John; Williams, Stephen B.; Quale, Diane Zipursky; Rosenberg, Jonathan E.

    2016-01-01

    The 10th Annual Bladder Cancer Think Tank was hosted by the Bladder Cancer Advocacy Network and brought together a multidisciplinary group of clinicians, researchers, representatives and Industry to advance bladder cancer research efforts. Think Tank expert panels, group discussions, and networking opportunities helped generate ideas and strengthen collaborations between researchers and physicians across disciplines and between institutions. Interactive panel discussions addressed a variety of timely issues: 1) data sharing, privacy and social media; 2) improving patient navigation through therapy; 3) promising developments in immunotherapy; 4) and moving bladder cancer research from bench to bedside. Lastly, early career researchers presented their bladder cancer studies and had opportunities to network with leading experts. PMID:27376139

  16. Upregulated UHRF1 Promotes Bladder Cancer Cell Invasion by Epigenetic Silencing of KiSS1

    PubMed Central

    Zhu, Zhiqiang; Zheng, Xin; Liu, Jianwei; Han, Zhiyou; Ma, Xuetao; Zhang, Yuhai

    2014-01-01

    Ubiquitin-like with PHD and RING finger domains 1 (UHRF1), as an epigenetic regulator, plays important roles in the tumorigenesis and cancer progression. KiSS1 functions as a metastasis suppressor in various cancers, and epigenetic silencing of KiSS1 increases the metastatic potential of cancer cells. We therefore investigated whether UHRF1 promotes bladder cancer cell invasion by inhibiting KiSS1. The expression levels of UHRF1 and KiSS1 were examined by quantitative real-time PCR assay in vitro and in vivo. The role of UHRF1 in regulating bladder cancer metastasis was evaluated in bladder cancer cell. We found that UHRF1 levels are upregulated in most clinical specimens of bladder cancer when compared with paired normal tissues, and UHRF1 expression levels are significantly increased in primary tumors that subsequently metastasized compared with non-metastatic tumors. Forced expression of UHRF1 promotes bladder cancer cell invasion, whereas UHRF1 knockdown decreases cell invasion. Overexpression of UHRF1 increases the methylation of CpG nucleotides and reduces the expression of KiSS1. UHRF1 and KiSS1 expression level is negatively correlated in vivo and in vitro. Knockdown of KiSS1 promotes bladder cancer cell invasion. Importantly, forced expression of KiSS1 partly abrogates UHRF1-induced cell invasion. These data demonstrated that upregulated UHRF1 increases bladder cancer cell invasion by epigenetic silencing of KiSS1. PMID:25272010

  17. Upregulated UHRF1 promotes bladder cancer cell invasion by epigenetic silencing of KiSS1.

    PubMed

    Zhang, Yu; Huang, Zhen; Zhu, Zhiqiang; Zheng, Xin; Liu, Jianwei; Han, Zhiyou; Ma, Xuetao; Zhang, Yuhai

    2014-01-01

    Ubiquitin-like with PHD and RING finger domains 1 (UHRF1), as an epigenetic regulator, plays important roles in the tumorigenesis and cancer progression. KiSS1 functions as a metastasis suppressor in various cancers, and epigenetic silencing of KiSS1 increases the metastatic potential of cancer cells. We therefore investigated whether UHRF1 promotes bladder cancer cell invasion by inhibiting KiSS1. The expression levels of UHRF1 and KiSS1 were examined by quantitative real-time PCR assay in vitro and in vivo. The role of UHRF1 in regulating bladder cancer metastasis was evaluated in bladder cancer cell. We found that UHRF1 levels are upregulated in most clinical specimens of bladder cancer when compared with paired normal tissues, and UHRF1 expression levels are significantly increased in primary tumors that subsequently metastasized compared with non-metastatic tumors. Forced expression of UHRF1 promotes bladder cancer cell invasion, whereas UHRF1 knockdown decreases cell invasion. Overexpression of UHRF1 increases the methylation of CpG nucleotides and reduces the expression of KiSS1. UHRF1 and KiSS1 expression level is negatively correlated in vivo and in vitro. Knockdown of KiSS1 promotes bladder cancer cell invasion. Importantly, forced expression of KiSS1 partly abrogates UHRF1-induced cell invasion. These data demonstrated that upregulated UHRF1 increases bladder cancer cell invasion by epigenetic silencing of KiSS1.

  18. Radical cystectomy with or without prior irradiation in the treatment of bladder cancer.

    PubMed

    Whitmore, W F; Batata, M A; Ghoneim, M A; Grabstald, H; Unal, A

    1977-01-01

    This is a summary presentation on certain aspects of an experience with the use of radical cystectomy with or without prior irradiation in the treatment of selected patients with bladder cancer at the Memorial Sloan-Kettering Cancer Center.

  19. Transvaginal Sonography Versus Cystoscopy for Detecting Urinary Bladder Invasion in Early Stage Cervical Cancer

    PubMed Central

    Zutshi, Vijay; Garg, Anju; Batra, Swaraj

    2017-01-01

    Introduction Cervical cancer is a major cause of mortality from cancer among women. In it’s early stage pre operative staging with cystoscopy is a standard procedure for the detection of urinary bladder involvement. Aim The present study was conducted with the aim to compare the efficacy of Transvaginal Sonography (TVS) and cystoscopy in diagnosing bladder involvement in early stage cervical cancer patients by confirming it intraoperatively and further by histopathologic examination. Materials and Methods A prospective partially blinded study was conducted between March 2006 and September 2008 on 30 patients with early stage cervical cancer (Stage I and IIa) who were planned to undergo radical hysterectomy. Pre operatively, these patients underwent both TVS and cystoscopy to diagnose bladder involvement. Presence or absence of bladder involvement was then confirmed intra operatively and by histopathologic examination. Results In all the 30 patients studied, no bladder involvement was seen on cystoscopy where as TVS showed bladder involvement in three patients. Involvement of the bladder in these three patients was confirmed intra operatively and by histopathologic examination. Thus, in our study, TVS was 100% sensitive in detecting bladder involvement. Conclusion TVS is highly sensitive in diagnosing bladder involvement in early stage cervical cancer and could potentially detect cases missed with a cystoscopy.

  20. Ultraviolet B Irradiance and Incidence Rates of Bladder Cancer in 174 Countries

    DTIC Science & Technology

    2010-03-01

    Schistosoma hemato- bium is highly prevalent in Egypt, 35 and chronic infection with it has been shown to substantially increase risk of bladder cancer ...rates of bladder cancer in a few European countries may be due in part to the extremely high prevalence of cigarette smok- ing in those countries in the...Ferlay J, Bray F, Pisani P, Parkin D. GLOHOCAN 2002: cancer inci- dence, mortality and prevalence worldwide. IARC Cancer Base No.5. version 2.0. www

  1. Endoscopic Gold Fiducial Marker Placement into the Bladder Wall to Optimize Radiotherapy Targeting for Bladder-Preserving Management of Muscle-Invasive Bladder Cancer: Feasibility and Initial Outcomes

    PubMed Central

    Garcia, Maurice M.; Gottschalk, Alexander R.; Brajtbord, Jonathan; Konety, Badrinath R.; Meng, Maxwell V.; Roach, Mack; Carroll, Peter R.

    2014-01-01

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

  2. Long term protection in bladder cancer following intralesional immunotherapy.

    PubMed

    Reichert, D F; Lamm, D L

    1984-09-01

    Despite effective treatment of existing tumors, patients with bladder cancer remain at risk of developing new tumors. Effective immunotherapy may lower that risk. To test this hypothesis, mice that had survived transitional cell carcinoma (MBT2) transplantation with the aid of bacillus Calmette-Guerin immunotherapy were randomized and tested for long term protective immunity against bladder carcinoma. Fifty-one tumor-free mice that had survived tumor challenge 10 to 15 months previously were randomized into 3 groups to receive intradermal tumor .noculation and intraperitoneal levamisole, intralesional Tice strain bacillus Calmette-Guerin, or intralesional saline. Fifteen previously unchallenged animals also received tumor and intralesional saline. All 3 groups of survivors had less tumor growth (p less than 0.01) than nonsurviving controls. Even among survivors, additional bacillus Calmette-Guerin immunization, but not levamisole treatment, significantly inhibited tumor growth (p less than 0.01). A 2nd experiment compared 22 nonimmune mice, 21 mice preimmunized intravenously with 300 micrograms of bacillus Calmette-Guerin cell walls, and 18 mice that had survived MBT2 by 8 months after live bacillus Calmette-Guerin treatment. Nonimmune and survivor groups were randomly subdivided into saline or treatment groups. Cell wall-preimmunized mice were divided into matching groups according to footpad response to purified protein derivative. The cell-wall preimmunized and nonimmune mice received the immunostimulant P3+Re-glycolipid or the carrier solution alone. The group of survivors received either intralesional saline or live bacillus Calmette-Guerin. Both bacillus Calmette-Guerin and saline-treated groups had significantly less tumor growth (p less than 0.001) than nonsurviving controls. Animals treated with P3-Re-glycolipid (with or without preimmunization with cell wall) did not differ from nonsurviving control. Footpad response to purified protein derivative did not

  3. Coffee consumption, genetic susceptibility and bladder cancer risk

    PubMed Central

    Villanueva, Cristina M.; Silverman, Debra T; Murta-Nascimento, Cristiane; Malats, Núria; Garcia-Closas, Montserrat; Castro, Francesc; Tardon, Adonina; Garcia-Closas, Reina; Serra, Consol; Carrato, Alfredo; Rothman, Nathaniel; Real, Francisco X; Dosemeci, Mustafa; Kogevinas, Manolis

    2010-01-01

    Objective We evaluated the bladder cancer risk associated with coffee consumption in a case-control study in Spain and examined the gene-environment interactions for genetic variants of caffeine metabolizing enzymes. Methods The analyses included 1136 incident cases with urothelial carcinoma of the urinary bladder and 1138 controls. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for area, age, gender, amount of cigarette smoking and years since quitting among former smokers. Results The OR (95%CI) for ever consumed coffee was 1.25 (0.95–1.64). For consumers of 1, 2, 3 and 4 or more cups/day relative to never drinkers, OR were, respectively: 1.24 (0.92–1.66), 1.11 (95%CI 0.82–1.51), 1.57 (1.13–2.19) and 1.27 (0.88–1.81). Coffee consumption was higher in smokers compared to never smokers. The OR for drinking at least 4 cups/day was: 1.13 (0.61–2.09) in current smokers, 1.57 (0.86–2.90) in former smokers, and 1.23 (0.55–2.76) in never smokers. Gene-coffee interactions evaluated in NAT2, CYP1A2, and CYP2E1-02 and CYP1A1 were not identified after adjusting for multiple testing. Conclusion The modest increased bladder cancer risk among coffee drinkers supports the hypothesis that coffee is a weak carcinogen, although results may, in part, be explained by residual confounding by smoking. The findings from the gene-coffee interactions need replication in further studies. PMID:18798002

  4. The Promise of Novel Molecular Markers in Bladder Cancer

    PubMed Central

    Miremami, Jahan; Kyprianou, Natasha

    2014-01-01

    Bladder cancer is the fourth most common malignancy in the US and is associated with the highest cost per patient. A high likelihood of recurrence, mandating stringent surveillance protocols, has made the development of urinary markers a focus of intense pursuit with the hope of decreasing the burden this disease places on patients and the healthcare system. To date, routine use of markers is not recommended for screening or diagnosis. Interests include the development of a single urinary marker that can be used in place of or as an adjunct to current screening and surveillance techniques, as well identifying a molecular signature for an individual’s disease that can help predict progression, prognosis, and potential therapeutic response. Markers have shown potential value in improving diagnostic accuracy when used as an adjunct to current modalities, risk-stratification of patients that could aid the clinician in determining aggressiveness of surveillance, and allowing for a decrease in invasive surveillance procedures. This review discusses the current understanding of emerging biomarkers, including miRNAs, gene signatures and detection of circulating tumor cells in the blood, and their potential clinical value in bladder cancer diagnosis, as prognostic indicators, and surveillance tools, as well as limitations to their incorporation into medical practice. PMID:25535079

  5. Multiplatform Biomarker Discovery for Bladder Cancer Recurrence Diagnosis

    PubMed Central

    De Paoli, Marine; Gogalic, Selma; Sauer, Ursula; Preininger, Claudia; Pandha, Hardev; Simpson, Guy; Horvath, Andras

    2016-01-01

    Purpose. Nonmuscle invasive bladder cancer (BCa) has a high recurrence rate requiring lifelong surveillance. Urinary biomarkers are promising as simple alternatives to cystoscopy for the diagnosis of recurrent bladder cancer. However, no single marker can achieve the required accuracy. The purpose of this study was to select a multiparameter panel, comprising urinary biomarkers and clinical parameters, for BCa recurrence diagnosis. Experimental Design. Candidate biomarkers were measured in urine samples of BCa patients with recurrence and BCa patients without recurrence. A multiplatform strategy was used for marker quantification comprising a multiplexed microarray and an automated platform for ELISA analysis. A multivariate statistical analysis combined the results from both platforms with the collected clinical data. Results. The best performing combination of biomarkers and clinical parameters achieved an AUC value of 0.91, showing better performance than individual parameters. This panel comprises six biomarkers (cadherin-1, IL-8, ErbB2, IL-6, EN2, and VEGF-A) and three clinical parameters (number of past recurrences, number of BCG therapies, and stage at time of diagnosis). Conclusions. The multiparameter panel could be a useful noninvasive tool for BCa surveillance and potentially impact the clinical management of this disease. Validation of results in an independent cohort is warranted. PMID:27660385

  6. The Role of Transurethral Resection in Trimodal Therapy for Muscle-Invasive Bladder Cancer

    PubMed Central

    Russell, Christopher M.; Lebastchi, Amir H.; Borza, Tudor; Spratt, Daniel E.; Morgan, Todd M.

    2016-01-01

    While radical cystectomy (RC) with pelvic lymph node dissection (PLND) represents the accepted gold standard for the treatment of muscle-invasive bladder cancer, this treatment approach is associated with significant morbidity. As such, bladder preservation strategies are often utilized in patients who are either deemed medically unfit due to significant comorbidities or whom decline management with RC and PLND secondary to its associated morbidity. In a select group of patients, meeting strict criteria, bladder preservation approaches may be employed with curative intent. Trimodal therapy, consisting of complete transurethral resection of bladder tumor (TURBT), chemotherapy, and radiation therapy has demonstrated durable oncologic control and long-term survival in a number of studies. The review presented here provides a description of trimodal therapy and the role of TURBT in bladder preservation for patients with muscle-invasive bladder cancer. PMID:28035319

  7. Bladder Cancer Molecular Taxonomy: Summary from a Consensus Meeting.

    PubMed

    Lerner, Seth P; McConkey, David J; Hoadley, Katherine A; Chan, Keith S; Kim, William Y; Radvanyi, François; Höglund, Mattias; Real, Francisco X

    2016-01-07

    The advent of Omics technologies has been key to the molecular subclassification of urothelial bladder cancer. Several groups have used different strategies to this aim, with partially overlapping findings. The meeting at the Spanish National Cancer Research Center-CNIO was held to discuss such classifications and reach consensus where appropriate. After updated presentations on the work performed by the teams attending the meeting, a consensus was reached regarding the existence of a group of Basal-Squamous-like tumors - designated BASQ - charaterized the high expression of KRT5/6 and KRT14 and low/undetectable expression of FOXA1 and GATA3. An additional tumor subgroup with urothelial differentiation features was recognized whose optimal molecular definition is required. For other subtypes described, more work is needed to determine how robust they are and how to best define them at the molecular level.

  8. Discrimination of healthy and cancer cells of the bladder by metabolic state, based on autofluorescence

    NASA Astrophysics Data System (ADS)

    Palmer, S.; Litvinova, Karina; Rafailov, E. U.; Nabi, G.

    2015-02-01

    Bladder cancer is among the most common cancers worldwide (4th in men). It is responsible for high patient morbidity and displays rapid recurrence and progression. Lack of sensitivity of gold standard techniques (white light cystoscopy, voided urine cytology) means many early treatable cases are missed. The result is a large number of advanced cases of bladder cancer which require extensive treatment and monitoring. For this reason, bladder cancer is the single most expensive cancer to treat on a per patient basis. In recent years, autofluorescence spectroscopy has begun to shed light into disease research. Of particular interest in cancer research are the fluorescent metabolic cofactors NADH and FAD. Early in tumour development, cancer cells often undergo a metabolic shift (the Warburg effect) resulting in increased NADH. The ratio of NADH to FAD ("redox ratio") can therefore be used as an indicator of the metabolic status of cells. Redox ratio measurements have been used to differentiate between healthy and cancer breast cells and to monitor cellular responses to therapies. Here, we have demonstrated, using healthy and bladder cancer cell lines, a statistically significant difference in the redox ratio of bladder cancer cells, indicative of a metabolic shift. To do this we customised a standard flow cytometer to excite and record fluorescence specifically from NADH and FAD, along with a method for automatically calculating the redox ratio of individual cells within large populations. These results could inform the design of novel probes and screening systems for the early detection of bladder cancer.

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

    PubMed

    Xylinas, Evanguelos; Hassler, Melanie R; Zhuang, Dazhong; Krzywinski, Martin; Erdem, Zeynep; Robinson, Brian D; Elemento, Olivier; Clozel, Thomas; Shariat, Shahrokh F

    2016-09-02

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

  10. Intervention of nicotine on MNU-induced bladder cancer in rats.

    PubMed

    Liu, Di; Pan, Feng; Li, Bing; Han, Xiaomin; Li, Wencheng; Shi, Ying; Pang, Zili; Zhang, Qijun

    2011-02-01

    This study examined the effect of nicotine on the expression of mutant p53 (mt-p53) in bladder cancer rats. The rat models of bladder cancer were established by infusing N-methyl-nitroso-urea (MNU, 10 mg/kg every 2 weeks for 8 weeks) into the bladder. Pathological examination on the bladder was conducted to confirm the establishment of the model. All the bladder cancer rats were randomly divided into an MNU group and 3 nicotine groups. In the nicotine groups, the rats were intragastrically administered nicotine at different concentrations (25, 15, 5 mg/kg respectively) 3 times per week for 8 weeks. The mt-p53 expression was detected by the immunohistochemical method. The results showed that rat bladder cancer models developed histopathological changes of bladder transitional cell carcinoma. The positive rate of mt-p53 expression in the 3 nicotine groups (25, 15, 5 mg/kg) was 75.00%, 58.33% and 41.67% by the 14th week, respectively, significantly higher than that in the MNU group (33.33%) (all P<0.05). The mt-p53 expression rate was positively correlated with the medication dose and time (P<0.05). It is concluded that nicotine may play an important role in the development of bladder cancer partially by increasing the expression of mt-p53.

  11. JNK2 downregulation promotes tumorigenesis and chemoresistance by decreasing p53 stability in bladder cancer

    PubMed Central

    Zhao, Yu; Qian, Chenchen; Wang, Liguo; Qi, Jun

    2016-01-01

    Bladder cancer is one of the most common malignancies of the urinary system, and the 5-year survival rate remains low. A comprehensive understanding of the carcinogenesis and progression of bladder cancer is urgently needed to advance treatment. c-Jun N-terminal kinase-2 (JNK2) exhibits both tumor promoter and tumor suppressor actions, depending on tumor type. Here, we analyzed the JNK2 function in bladder cancer. Using gene expression microarrays, we demonstrated that JNK2 mRNA is downregulated in an orthotopic rat model of bladder cancer. JNK2 protein levels were lower in rat and human bladder cancer tissues than in normal tissues, and the levels correlated with those of p53. Moreover, JNK2 phosphorylated p53 at Thr-81, thus protecting p53 from MDM2-induced proteasome degradation. Decreased expression of JNK2 in T24 cells conferred resistance to cell death induced by mitomycin C. Furthermore, lower JNK2 expression was associated with poorer overall survival among patients who underwent radical cystectomy. These results indicate that JNK2 acts as a tumor suppressor in bladder cancer, and that decreased JNK2 expression promotes bladder cancer tumorigenesis. PMID:27147566

  12. Collecting and Studying Blood and Tissue Samples From Patients With Locally Recurrent or Metastatic Prostate or Bladder/Urothelial Cancer

    ClinicalTrials.gov

    2016-12-06

    Healthy Control; Localized Urothelial Carcinoma of the Renal Pelvis and Ureter; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Prostate Cancer

  13. The Role of Interferon in the Management of BCG Refractory Nonmuscle Invasive Bladder Cancer

    PubMed Central

    Correa, Andres F.; Theisen, Katherine; Ferroni, Matthew; Maranchie, Jodi K.; Hrebinko, Ronald; Davies, Benjamin J.; Gingrich, Jeffrey R.

    2015-01-01

    Background. Thirty to forty percent of patients with high grade nonmuscle invasive bladder cancer (NMIBC) fail to respond to intravesical therapy with bacillus Calmette-Guerin (BCG). Interferon-α2B plus BCG has been shown to be effective in a subset of patients with NMIBC BCG refractory disease. Here we present a contemporary series on the effectiveness and safety of intravesical BCG plus interferon-α2B therapy in patients with BCG refractory NMIBC. Methods. From January of 2005 to April of 2014 we retrospectively found 44 patients who underwent induction with combination IFN/BCG for the management of BCG refractory NMIBC. A chart review was performed to assess initial pathological stage/grade, pathological stage/grade at the time of induction, time to IFN/BCG failure, pathological stage/grade at failure, postfailure therapy, and current disease state. Results. Of the 44 patients who met criteria for the analysis. High risk disease was found in 88.6% of patients at induction. The 12-month and 24-month recurrence-free survival were 38.6% and 18.2%, respectively. 25 (56.8%) ultimately had disease recurrence. Radical cystectomy was performed in 16 (36.4%) patients. Conclusion. Combination BCG plus interferon-α2B remains a reasonably safe alternative treatment for select patients with BCG refractory disease prior to proceeding to radical cystectomy. PMID:26550012

  14. [Peculiarities of urinary bladder cancer tumor cells apoptosis response on neoadjuvant chemotherapy].

    PubMed

    Iatsyna, A I; Stakhovskiĭ, É A; Sheremet, Ia A; Spivak, S I; Stakhovskiĭ, A É; Gavriliuk, O N; Vitruk, Iu V; Emets, A I; Blium, Ia B

    2011-01-01

    Induced apoptosis in urinary bladder cancer tumor cells of patients was studied using TUNEL reaction. It was shown that increase in induced apoptosis value had a definite correlation between corresponding features of tumor reaction as a response on Gemcitabine-Cisplatin neoadjuvant chemotherapy application. It was found that evaluation of induced apoptosis in urinary bladder cancer tumor cells using TUNEL method allows forecasting the effectiveness of chemotherapy on the cellular level in patients with this type of cancer.

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

    selection between automatic bladder segmentation and manual delineation was 56.7%. The automatic segmentation and visual assessment took on average 7.8 and 9.7 s, respectively. In 53.4% of the cases, manual correction was performed after automatic segmentation. The manual correction improved the mean CI overlap, mean residual error and plan selection agreement to 77.7%, 0.30 cm and 80.7%, respectively. Manual correction required on average 8.4 markers and took on average 35.5 s. The statistical shape-based segmentation approach allows automatic segmentation of the bladder on CBCT with moderate accuracy. Limited user intervention can quickly and reliably improve the bladder contours. This segmentation method is suitable to select the appropriate plan for multiple-plan ART of bladder cancer.

  16. Comparative Tissue Proteomics of Microdissected Specimens Reveals Novel Candidate Biomarkers of Bladder Cancer*

    PubMed Central

    Chen, Chien-Lun; Chung, Ting; Wu, Chih-Ching; Ng, Kwai-Fong; Yu, Jau-Song; Tsai, Cheng-Han; Chang, Yu-Sun; Liang, Ying; Tsui, Ke-Hung; Chen, Yi-Ting

    2015-01-01

    More than 380,000 new cases of bladder cancer are diagnosed worldwide, accounting for ∼150,200 deaths each year. To discover potential biomarkers of bladder cancer, we employed a strategy combining laser microdissection, isobaric tags for relative and absolute quantitation labeling, and liquid chromatography-tandem MS (LC-MS/MS) analysis to profile proteomic changes in fresh-frozen bladder tumor specimens. Cellular proteins from four pairs of surgically resected primary bladder cancer tumor and adjacent nontumorous tissue were extracted for use in two batches of isobaric tags for relative and absolute quantitation experiments, which identified a total of 3220 proteins. A DAVID (database for annotation, visualization and integrated discovery) analysis of dysregulated proteins revealed that the three top-ranking biological processes were extracellular matrix organization, extracellular structure organization, and oxidation-reduction. Biological processes including response to organic substances, response to metal ions, and response to inorganic substances were highlighted by up-expressed proteins in bladder cancer. Seven differentially expressed proteins were selected as potential bladder cancer biomarkers for further verification. Immunohistochemical analyses showed significantly elevated levels of three proteins—SLC3A2, STMN1, and TAGLN2—in tumor cells compared with noncancerous bladder epithelial cells, and suggested that TAGLN2 could be a useful tumor tissue marker for diagnosis (AUC = 0.999) and evaluating lymph node metastasis in bladder cancer patients. ELISA results revealed significantly increased urinary levels of both STMN1 and TAGLN2 in bladder cancer subgroups compared with control groups. In comparisons with age-matched hernia urine specimens, urinary TAGLN2 in bladder cancer samples showed the largest fold change (7.13-fold), with an area-under-the-curve value of 0.70 (p < 0.001, n = 205). Overall, TAGLN2 showed the most significant

  17. Comparison of adaptive radiotherapy techniques for external radiation therapy of canine bladder cancer.

    PubMed

    Nieset, Jessica R; Harmon, Joseph F; Johnson, Thomas E; Larue, Susan M

    2014-01-01

    Daily bladder variations make it difficult to utilize standard radiotherapy as a primary treatment option for muscle-invasive bladder cancer. Our purpose was to develop a model comparing dose distributions of image-guided and adaptive radiotherapy (ART) techniques for canine bladder cancer. Images were obtained retrospectively from cone-beam computed tomography (CBCT) scans used for daily positioning of four dogs undergoing fractionated image-guided radiotherapy (IGRT). Four different treatment plans were modeled for each dog, and dosimetric data were compared. Two plans were developed using planning target volumes based on planning computed tomography (CT) bladder volume. These plans then used bony anatomy or soft tissue anatomy for daily positioning and dosimetric modeling. The third plan type was a hybrid IGRT and ART technique utilizing a library of premade anisotropic planning target volumes using bladder wall motion data and selection of a "plan-of-the-day" determined from positioning CBCT bladder volumes. The fourth plan was an ART technique that constructed a new planning target volume each day based on daily bladder volume as determined by pretreatment CBCT. Dose volume histograms were generated for each plan type and dose distribution for the bladder and rectum were compared between plan types. Irradiated rectal volume decreased and irradiated bladder volume increased as plan conformality increased. ART provided the greatest rectal sparing, with lowest irradiated rectal volume (P < 0.001), and largest bladder volume receiving 95% of the prescription dose (P < 0.001). In our model, adaptive radiotherapy techniques for canine bladder cancer showed significant reduction in rectal volume irradiated when compared to nonadaptive techniques, while maintaining appropriate bladder coverage.

  18. Beyond proliferation: KLF5 promotes angiogenesis of bladder cancer through directly regulating VEGFA transcription.

    PubMed

    Gao, Yang; Wu, Kaijie; Chen, Yule; Zhou, Jiancheng; Du, Chong; Shi, Qi; Xu, Shan; Jia, Jing; Tang, Xiaoshuang; Li, Feng; Hui, Ke; He, Dalin; Guo, Peng

    2015-12-22

    Abundant evidence has demonstrated critical roles of KLF5 in regulating cell proliferation in various cancers, however, its additional roles in other aspects of cancer development remain to be further clarified. In this study, we found that KLF5 was essential for cancer cell-endothelial cell interaction in vitro and tumor angiogenesis in nude mice based on lentivirus-mediated KLF5 knockdown bladder cancer cell models. Moreover, KLF5 insufficiency abolished the ability of bladder cancer cells to induce neovascularization in rabbit cornea. Mechanistically, the pro-angiogenic factor VEGFA was identified as a direct downstream target of KLF5, which bound to GC-boxes and CACCC elements of VEGFA promoter and regulated its transcriptional activity. In addition, there was a positive correlation between KLF5 and VEGFA expression in human bladder cancer tissues by immunohistochemistry assay and statistical analysis from TCGA and GEO data. Furthermore, we found that two pivotal pathways in bladder cancer, RTKs/RAS/MAPK and PI3K/Akt, might convey their oncogenic signaling through KLF5-VEGFA axis. Taken together, our results indicate that KLF5 promotes angiogenesis of bladder cancer through directly regulating VEGFA transcription and suggest that KLF5 could be a novel therapeutic target for angiogenesis inhibition in bladder cancer.

  19. Beyond proliferation: KLF5 promotes angiogenesis of bladder cancer through directly regulating VEGFA transcription

    PubMed Central

    Chen, Yule; Zhou, Jiancheng; Du, Chong; Shi, Qi; Xu, Shan; Jia, Jing; Tang, Xiaoshuang; Li, Feng; Hui, Ke; He, Dalin; Guo, Peng

    2015-01-01

    Abundant evidence has demonstrated critical roles of KLF5 in regulating cell proliferation in various cancers, however, its additional roles in other aspects of cancer development remain to be further clarified. In this study, we found that KLF5 was essential for cancer cell-endothelial cell interaction in vitro and tumor angiogenesis in nude mice based on lentivirus-mediated KLF5 knockdown bladder cancer cell models. Moreover, KLF5 insufficiency abolished the ability of bladder cancer cells to induce neovascularization in rabbit cornea. Mechanistically, the pro-angiogenic factor VEGFA was identified as a direct downstream target of KLF5, which bound to GC-boxes and CACCC elements of VEGFA promoter and regulated its transcriptional activity. In addition, there was a positive correlation between KLF5 and VEGFA expression in human bladder cancer tissues by immunohistochemistry assay and statistical analysis from TCGA and GEO data. Furthermore, we found that two pivotal pathways in bladder cancer, RTKs/RAS/MAPK and PI3K/Akt, might convey their oncogenic signaling through KLF5-VEGFA axis. Taken together, our results indicate that KLF5 promotes angiogenesis of bladder cancer through directly regulating VEGFA transcription and suggest that KLF5 could be a novel therapeutic target for angiogenesis inhibition in bladder cancer. PMID:26544730

  20. Bladder preservation in non-metastatic muscle-invasive bladder cancer (MIBC): a single-institution experience.

    PubMed

    Gerardi, Marianna A; Jereczek-Fossa, Barbara A; Zerini, Dario; Surgo, Alessia; Dicuonzo, Samantha; Spoto, Ruggero; Fodor, Cristiana; Verri, Elena; Rocca, Maria Cossu; Nolè, Franco; Muto, Matteo; Ferro, Matteo; Musi, Gennaro; Bottero, Danilo; Matei, Deliu V; De Cobelli, Ottavio; Orecchia, Roberto

    2016-01-01

    The aim of this study is to access the feasibility, toxicity profile, and tumour outcome of an organ preservation curative approach in non-metastatic muscle-invasive bladder cancer. A retrospective analysis was conducted on patients affected by M0 bladder cancer, who refused cystectomy and were treated with a curative approach. The standard bladder preservation scheme included maximal transurethral resection of bladder tumour (TURBT) and combination of radiotherapy and platin-based chemotherapy, followed by endoscopic evaluation, urine cytology, and instrumental evaluation. Thirteen patients fulfilled the inclusion criteria. TNM stage was cT2cN0M0 and cT2cNxM0, in 12 and one patients, respectively. All patients had transitional cell cancer. Twelve patients completed the whole therapeutic programme (a bimodal treatment without chemotherapy for one patient). Median follow-up is 36 months. None of the patients developed severe urinary or intestinal acute toxicity. In 10 patients with a follow-up > 6 months, no cases of severe late toxicity were observed. Response evaluated in 12 patients included complete response and stable disease in 11 patients (92%), and one patient (8%), respectively. At the time of data analysis (March 2016), 10 patients (77%) are alive with no evidence of disease, two patients (15%) died for other reasons, and one patient has suspicious persistent local disease. The trimodality approach, including maximal TURBT, radiotherapy, and chemotherapy for muscle-invasive bladder cancer, is well-tolerated and might be considered a valid and feasible option in fit patients who refuse radical cystectomy.

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

    PubMed

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

    2016-02-01

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

  2. Statistical consideration for clinical biomarker research in bladder cancer

    PubMed Central

    Shariat, Shahrokh F.; Lotan, Yair; Vickers, Andrew; Karakiewicz, Pierre I.; Schmitz-Dräger, Bernd J.; Goebell, Peter J.; Malats, Nuria

    2012-01-01

    Purpose To critically review and illustrate current methodologic and statistical considerations for bladder cancer biomarker discovery and evaluation. Methods Original, review, and methodological articles, and editorials were reviewed and summarized. Results Biomarkers may be useful at multiple stages of bladder cancer management: early detection, diagnosis, staging, prognosis, and treatment; however, few novel biomarkers are currently used in clinical practice. The reasons for this disjunction are manifold and reflect the long and difficult pathway from candidate biomarker discovery to clinical assay, and the lack of coherent and comprehensive processes (pipelines) for biomarker development. Conceptually, the development of new biomarkers should be a process that is similar to therapeutic drug evaluation - a highly regulated process with carefully regulated phases from discovery to human applications. In a further effort to address the pervasive problem of inadequacies in the design, analysis, and reporting of biomarker prognostic studies, a set of reporting recommendations are discussed. For example, biomarkers should provide unique information that adds to known clinical and pathologic information. Conventional multivariable analyses are not sufficient to demonstrate improved prediction of outcomes. Predictive models, including or excluding any new putative biomarker, needs to show clinically significant improvement of performance in order to claim any real benefit. Towards this end, proper model building, avoidance of overfitting, and external validation are crucial. In addition, it is important to choose appropriate performance measures dependent on outcome and prediction type and to avoid use of cut-points. Biomarkers providing a continuous score provide potentially more useful information than cut-points since risk fits a continuum model. Combination of complementary and independent biomarkers is likely to better capture the biologic potential of a tumor

  3. Environmental non-occupational risk factors associated with bladder cancer

    PubMed Central

    Ferrís, J.; Berbel, O.; Alonso-López, J.; Garcia, J.; Ortega, J.A.

    2016-01-01

    Context Bladder carcinoma (BC), due its high morbidity and relapsing course, generates significant economic and health care costs. Accordingly, we reviewed the environmental nonoccupational risk factors (RF), more or less evidence-based, in the etiology and pathogenesis of BC, because the involvement of urologists is essential for prevention. Acquisition of evidence Review of the peer-reviewed literature (1987–2012) on nonoccupational environmental RF associated with BC retrieved from Medline, Embase and Science Citation Index. The search profiles have been “Risk factors/Epidemiology/Tobacco-smoking/Diet-nutrition-water-liquids/Radiation/Infectious/Farmacological drugs” and “Bladder cancer”. Synthesis of evidence Smoking was associated with 50% of BC in both sexes. Smokers have a 2–5 times higher risk than nonsmokers, directly proportional to the amount and duration of addiction. Drinking water contaminated with arsenic and chromium chlorination byproducts increases the risk of BC. High consumption of red meat and saturated fat may increase the risk, while high intake of fruits and vegetables decreases it. Patients treated with cyclophosphamide, ifosfamide and ionizing radiation have an increased risk of BC. Frequent and prolonged use of hair dyes and Schistosoma haematobium infestation increases the risk of BC. Conclusions The reduction or the cessation of smoking decrease BC. The contaminant-free water consumption with the increase of vegetal foods favors BC prevention. Cancer survivors treated with cyclophosphamide, ifosfamide and radiation therapy should be monitored for early diagnosis of BC. PMID:23618510

  4. Histopathological and prognostic significance of the expression of sex hormone receptors in bladder cancer: A meta-analysis of immunohistochemical studies

    PubMed Central

    Ide, Hiroki; Inoue, Satoshi

    2017-01-01

    Objective Emerging preclinical evidence suggests the involvement of sex hormones and their receptor signals in the development and progression of bladder cancer. Meanwhile, previous studies have demonstrated conflicting results on the relationship between the status of sex hormone receptors in urothelial tumors and histopathological characteristics of the tumors or patient outcomes. We therefore conducted this meta-analysis to assess the clinicopathological impact of the expression of androgen receptor (AR) and estrogen receptors (ERs) in bladder cancer. Methods A comprehensive literature search in databases (i.e. PubMed, Web of Science, Cochrane) was performed for all immunohistochemical studies stained for AR, ERα, and/or ERβ in surgically resected bladder cancer specimens and analyzed for patient outcomes. We selected eligible studies in accordance with the PRISMA guidelines and analyzed data using R software. Results A total of 2,049 patients from 13 retrospective studies were included in this meta-analysis. The difference in ERα expression between non-tumors and tumors was significant [odds ratio (OR) = 0.412; P<0.001], while those of AR (OR = 3.256; P = 0.336) or ERβ (OR = 0.580; P = 0.674) were not statistically significant. AR positivity in tumors was strongly correlated with gender (male vs. female: OR = 0.658; P = 0.027) or tumor grade (low-grade vs. high-grade: OR = 0.575; P<0.001). ERβ positive rates were significantly higher in high-grade (OR = 2.169; P<0.001) and muscle-invasive (OR = 3.104; P<0.001) tumors than in low-grade and non-muscle-invasive tumors, respectively. Survival analysis in patients with non-muscle-invasive bladder cancer revealed associations between AR expression and better recurrence-free survival [hazard ration (HR) = 0.593; P = 0.006) as well as between ERβ expression and worse recurrence-free (HR = 1.573; P = 0.013) or progression-free (HR = 4.148; P = 0.089) survivals. Conclusions These data suggest down-regulation of ER

  5. The health economics of bladder cancer: an updated review of the published literature.

    PubMed

    Yeung, Christina; Dinh, Tuan; Lee, Joseph

    2014-11-01

    The purpose of this paper is to provide a current view of the economic burden of bladder cancer, with a focus on the cost effectiveness of available interventions. This review updates a previous systematic review and includes 72 new papers published between 2000 and 2013. Bladder cancer continues to be one of the most common and expensive malignancies. The annual cost of bladder cancer in the USA during 2010 was $US4 billion and is expected to rise to $US5 billion by 2020. Ten years ago, urinary markers held the potential to lower treatment costs of bladder cancer. However, subsequent real-world experiments have demonstrated that further work is necessary to identify situations in which these technologies can be applied in a cost-effective manner. Adjunct cytology remains a part of diagnostic standard of care, but recent research suggests that it is not cost effective due to its low diagnostic yield. Analysis of intravesical chemotherapy after transurethral resection of bladder tumor (TURBT), neo-adjuvant therapy for cystectomy, and robot-assisted laparoscopic cystectomy suggests that these technologies are cost effective and should be implemented more widely for appropriate patients. The existing literature on the cost effectiveness of bladder cancer treatments has improved substantially since 2000. The body of work now includes many new models, registry analyses, and real-world studies. However, there is still a need for new implementation guidelines, new risk modeling tools, and a better understanding of the empirical burden of bladder cancer.

  6. A Polycomb-mir200 loop regulates clinical outcome in bladder cancer

    PubMed Central

    Feber, Andrew; Segovia, Cristina; García-Escudero, Ramón; Rubio, Carolina; López-Calderón, Fernando F.; Díaz-García, Claudio; Villacampa, Felipe; Duarte, José; Gómez-Rodriguez, María J.; Castellano, Daniel; Rodriguez-Peralto, José L.; de la Rosa, Federico; Beck, Stephan; Paramio, Jesús M.

    2015-01-01

    Bladder cancer (BC) is a highly prevalent disease, ranking fifth in the most common cancers worldwide. Various miRNAs have recently emerged as potential prognostic biomarkers in cancer. The miR-200 family, which repressed the epithelial-to-mesenchymal transition (EMT), is repressed in multiple advanced cancers. However, its expression and function in BC is still poorly understood. Here we show that miR-200 family displays increased expression, probably due to the activation of specific oncogenic signaling pathways, and reduced promoter methylation, in BC compared to normal bladder samples. Furthermore, we show that the expression of these miRNAs is decreased in high grade and stage tumors, and the down-regulation is associated with patient's poor clinical outcome. Our data indicate that the miR-200 family plays distinct roles in Non-Muscle (NMIBC) and Muscle-Invasive BC (MIBC). In MIBC, miR-200 expression post transcriptionally regulates EMT-promoting transcription factors ZEB1 and ZEB2, whereas suppresses BMI1 expression in NMIBC. Interestingly, we show that increased EZH2 and/or BMI1 expression repress the expression of miR-200 family members. Collectively, these findings support a model of BC progression through a coordinated action between the Polycomb Repression Complex (PRC) members repressing the miR-200 expression, which ultimately favors invasive BC development. Since pharmacological inhibition of EZH2 in BC cell lines lead to increased miR-200 expression, our findings may support new therapeutic strategies for BC clinical management. PMID:26517683

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

    PubMed Central

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

    2017-01-01

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

  8. Kaempferol suppresses bladder cancer tumor growth by inhibiting cell proliferation and inducing apoptosis.

    PubMed

    Dang, Qiang; Song, Wenbin; Xu, Defeng; Ma, Yanmin; Li, Feng; Zeng, Jin; Zhu, Guodong; Wang, Xinyang; Chang, Luke S; He, Dalin; Li, Lei

    2015-09-01

    The effects of the flavonoid compound, kaempferol, which is an inhibitor of cancer cell proliferation and an inducer of cell apoptosis have been shown in various cancers, including lung, pancreatic, and ovarian, but its effect has never been studied in bladder cancer. Here, we investigated the effects of kaempferol on bladder cancer using multiple in vitro cell lines and in vivo mice studies. The MTT assay results on various bladder cancer cell lines showed that kaempferol enhanced bladder cancer cell cytotoxicity. In contrast, when analyzed by the flow cytometric analysis, DNA ladder experiment, and TUNEL assay, kaempferol significantly was shown to induce apoptosis and cell cycle arrest. These in vitro results were confirmed in in vivo mice studies using subcutaneous xenografted mouse models. Consistent with the in vitro results, we found that treating mice with kaempferol significant suppression in tumor growth compared to the control group mice. Tumor tissue staining results showed decreased expressions of the growth related markers, yet increased expressions in apoptosis markers in the kaempferol treated group mice tissues compared to the control group mice. In addition, our in vitro and in vivo data showed kaempferol can also inhibit bladder cancer invasion and metastasis. Further mechanism dissection studies showed that significant down-regulation of the c-Met/p38 signaling pathway is responsible for the kaempferol mediated cell proliferation inhibition. All these findings suggest kaempferol might be an effective and novel chemotherapeutic drug to apply for the future therapeutic agent to combat bladder cancer.

  9. Risk based neoadjuvant chemotherapy in muscle invasive bladder cancer

    PubMed Central

    Jayaratna, Isuru S.; Navai, Neema

    2015-01-01

    Muscle invasive bladder cancer (MIBC) is an aggressive disease that frequently requires radical cystectomy (RC) to achieve durable cure rates. Surgery is most effective when performed in organ-confined disease, with the best outcomes for those patients with a pT0 result. The goals of neoadjuvant chemotherapy (NC) are to optimize surgical outcomes for a malignancy with limited adjuvant therapies and a lack of effective salvage treatments. Despite level 1 evidence demonstrating a survival benefit, the utilization of NC has been hampered by several issues, including, the inability to predict responders and the perception that NC may delay curative surgery. In this article, we review the current efforts to identify patients that are most likely to derive a benefit from NC, in order to create a risk-adapted paradigm that reserves NC for those who need it. PMID:26816830

  10. Occupation and bladder cancer: a death-certificate study.

    PubMed Central

    Dolin, P. J.; Cook-Mozaffari, P.

    1992-01-01

    Occupational statements on death certificates of 2,457 males aged 25-64 who died from bladder cancer in selected coastal and estaurine regions of England and Wales during 1965-1980 were studied. Excess mortality was found for deck and engine room crew of ships, railway workers, electrical and electronic workers, shoemakers and repairers, and tobacco workers. An excess of cases also occurred among food workers, particularly those employed in the bread and flour confectionary industry or involved in the extraction of animal and vegetable oils and fats. Use of a job-exposure matrix revealed elevated risk for occupations in which most workers were exposed to paints and pigments, benzene and cutting oils. PMID:1520596

  11. The impact of pioglitazone on bladder cancer and cardiovascular events.

    PubMed

    Lee, Esther J; Marcy, Todd R

    2014-08-01

    Type 2 diabetes mellitus (T2DM) is a chronic condition with increasing prevalence and severe complications. Thiazolidinediones have been marketed since 1997 and are effective glucose-lowering drugs, but individual drugs within the class have been linked to serious adverse effects that resulted in the removal of troglitazone from the market, restrictions to rosiglitazone's use, and a warning added to pioglitazone's label. In 2007, a meta-analysis linked rosiglitazone to myocardial infarction (MI). Pioglitazone does not appear to share this risk. To the contrary, pioglitazone may reduce risk for MI. However, retrospective evaluations have increasingly linked pioglitazone to a higher risk of bladder cancer that appears to be time- and dose-dependent. Pioglitazone remains a medication appropriate for consideration in the management of T2DM; however, clinicians and patients should weigh its risks compared with alternatives, with a regular review of risks.

  12. Controversies Related to Diabetes and Risk of Bladder Cancer.

    PubMed

    Spradling, Kyle; Youssef, Ramy F

    2016-03-15

    In recent years, a growing number of case-control and cohort studies have suggested that patients with diabetes mellitus (DM) may have a higher risk of developing bladder cancer (BC). However, the body of evidence linking DM and BC is controversial and largely composed of observational studies with significant heterogeneity in study design. In this review, we outline the current body of evidence associating DM with BC. We also highlight the evidence surrounding the relationship between BC and two antidiabetic medications, metformin and pioglitazone. Currently, not enough evidence is available to decisively conclude that DM is associated with an increased risk for development of BC. Similarly, the current body of evidence is inadequate to establish a causal relationship between pioglitazone and BC nor a protective relationship between metformin and BC.

  13. Clinical Outcomes in cT1 Micropapillary Bladder Cancer

    PubMed Central

    Willis, DL; Fernandez, MI; Dickstein, RJ; Parikh, S; Shah, JB; Pisters, LL; Guo, CC; Henderson, S; Czerniak, BA; Grossman, HB; Dinney, CP; Kamat, AM

    2015-01-01

    Purpose While many urologists recommend radical cystectomy for patient with micropapillary bladder cancer (MPBC) invading the lamina propria (cT1), contradictory small reports exist regarding the efficacy of conservative management with intravesical BCG for this disease. Herein we report our updated experience with largest series of patients with cT1 MPBC. Materials and Methods An IRB approved review of our cancer database identified 283 patients with MPBC, including 72 staged as cT1N0M0 at diagnosis and initiation of therapy. Survival analysis was performed using Kaplan-Meier estimator and compared using the log-rank test. Results Within this 72 patient cohort, 40 received primary intravesical BCG and 26 underwent upfront radical cystectomy. Patients receiving BCG experienced high rates of disease recurrence (75%) and progression (45%); 35% developed lymph node metastasis. Patients treated with upfront cystectomy had improved survival compared to patients treated with primary BCG (5 year disease specific survival (DSS) of 100% vs. 60% respectively, p=0.006) or patients undergoing delayed cystectomy after recurrence (5 yr. DSS: 62%, p=0.015). Prognosis was especially poor in patients who waited for progression prior to undergoing radical cystectomy, with an estimated 5-year DSS of only 24% and a median survival of 35 months. In patients treated with upfront cystectomy, pathologic upstaging occurred in 27%, including 20% with lymph node metastasis. Conclusions While certain patients with T1 MPBC may respond to intravesical BCG, improved survival is seen in those patients who undergo early radical cystectomy. Further molecular studies are needed to identify subsets of patients able to spare their bladders safely. PMID:25254936

  14. Therapeutic potential of thalidomide for gemcitabine-resistant bladder cancer.

    PubMed

    Huang, Yen Ta; Cheng, Chuan Chu; Chiu, Ted H; Lai, Pei Chun

    2015-11-01

    Controversial effects of thalidomide for solid malignancies have been reported. In the present study, we evaluate the effects of thalidomide for transitional cell carcinoma (TCC), the most common type of bladder cancer. Thalidomide precipitates were observed when its DMSO solution was added to the culture medium. No precipitation was found when thalidomide was dissolved in 45% γ-cyclodextrin, and this concentration of γ-cyclodextrin elicited slight cytotoxicity on TCC BFTC905 and primary human urothelial cells. Thalidomide-γ-cyclodextrin complex exerted a concentration-dependent cytotoxicity in TCC cells, but was relatively less cytotoxic (with IC50 of 200 µM) in BFTC905 cells than the other 3 TCC cell lines, possibly due to upregulation of Bcl-xL and HIF-1α mediated carbonic anhydrase IX, and promotion of quiescence. Gemcitabine-resistant BFTC905 cells were chosen for additional experiments. Thalidomide induced apoptosis through downregulation of survivin and securin. The secretion of VEGF and TNF-α was ameliorated by thalidomide, but they did not affect cell proliferation. Immune-modulating lenalidomide and pomalidomide did not elicit cytotoxicity. In addition, cereblon did not play a role in the thalidomide effect. Oxidative DNA damage was triggered by thalidomide, and anti-oxidants reversed the effect. Thalidomide also inhibited TNF-α induced invasion through inhibition of NF-κB, and downregulation of effectors, ICAM-1 and MMP-9. Thalidomide inhibited the growth of BFTC905 xenograft tumors in SCID mice via induction of DNA damage and suppression of angiogenesis. Higher average body weight, indicating less chachexia, was observed in thalidomide treated group. Sedative effect was observed within one-week of treatment. These pre-clinical results suggest therapeutic potential of thalidomide for gemcitabine-resistant bladder cancer.

  15. Comparison between standard and reduced volume radiotherapy in bladder preservation trimodality protocol for muscle-invasive bladder cancer patients

    PubMed Central

    Arafat, Waleed; Darwish, Azza; Naoum, George E; Sameh, Wael; Husseiny, Gamal El; Abd-El-Gawad, Fathy; Samir, Mostafa

    2016-01-01

    Aim Our aim is to compare the toxicity, pelvic nodal relapse, and overall survival of whole bladder irradiation only to the standard technique of whole pelvis irradiation followed by bladder boost in patients with muscle-invasive bladder carcinoma undergoing bladder preservation protocol. Material and method A total of 60 patients with transitional cell carcinoma, stage T2-3, N0, M0 bladder cancer were subjected to maximal transurethral resection bladder tumour (TURB). Then, the patients were randomised into two groups: group I (30 patients) to receive whole pelvis radiotherapy 44 Gy followed by 20 Gy bladder boost. While group II (30 patients) were randomised to receive whole bladder radiotherapy alone for a total dose of 64 Gy. In both groups, concomitant cisplatin and paclitaxel were given weekly throughout the whole course of radiotherapy where conventional 2 Gy/fraction were used. Additionally, four cycles of adjuvant cisplatin and paclitaxel were given after the end of the chemoradiotherapy induction course. Results The first assessment after the induction chemoradiotherapy showed that complete response was achieved in 73.3% of patients in group I and 76.7% of the patients in group II. After a median follow-up of 2 years, regional relapse occurred in 7.1% of patients in group I and 10.3% in group II. (p = 1). Distant metastases were detected in 17.9% of patient in group I and 13.8% in group II (p = 0.73). The 2-year disease-free survival was 60% in group I and 63.3% in group II (p = 0.79). The whole 2-year overall survival was 75% in group I and 79.3% in group II (p = 0.689). Radiation gastrointestinal (GI) acute toxicity was higher in group I than in group II (p = 0.001), while late GI radiation toxicity was comparable in both groups. Conclusion Treating the bladder only, without elective pelvic nodal irradiation, did not compromise pelvic control rate, but significantly decreased the acute radiation toxicity. PMID:27899955

  16. Rb knockdown accelerates bladder cancer progression through E2F3 activation.

    PubMed

    Wang, Jiang-Ping; Jiao, Yong; Wang, Cheng-Yuan; Xu, Zhi-Bin; Zhang, Bo

    2017-01-01

    Bladder cancer is one of the most common cancers diagnosed in the world and leads to significant mortality and morbidity among affected patients. The retinoblastoma (Rb) protein is a main tumor suppressor, controlling cellular responses to potentially oncogenic stimulation. E2F3 was invariably disrupted in different human cancers for its central role in the control of cellular proliferation. Here, we investigated how Rb is integrated to control bladder cancer progression through E2F3 and p53 regulation. The results exhibit that Rb expression is lower in patients with bladder tumor, while E2F3 level is high. Rb knockdown enhanced bladder tumor cell proliferation and migration, aggravated with p53 silence. Interestingly, Rb silence results in E2F3, Myc and mTOR signaling pathway activation, contributing to bladder cancer cell proliferation and apoptosis suppression mainly through caspase-3 inhibition in vitro and in vivo. Immunohistochemical analysis revealed that Rb is highly expressed in normal bladder cells, but was repressed in tumor tissues of the bladder completely, suggesting a possible role of Rb as a tumor suppressor.

  17. Risk factors for bladder cancer in a cohort exposed to aromatic amines

    SciTech Connect

    Schulte, P.A.; Ringen, K.; Hemstreet, G.P.; Altekruse, E.B.; Gullen, W.H.; Tillett, S.; Allsbrook, W.C. Jr.; Crosby, J.H.; Witherington, R.; Stringer, W.

    1986-11-01

    Occupational and nonoccupational risk factors for bladder cancer were analyzed in a cohort of 1385 workers with known exposure to a potent bladder carcinogen, beta-naphthylamine. Bladder cancer was approximately seven times (95% confidence interval (CI) = 3.9, 12.4) more likely in exposed rather than nonexposed individuals, yet, otherwise, the groups were generally similar in other exogenous or hereditary risk factors. A total of 13 cases of bladder cancer were identified. After the first year of a screening program involving 380 members of the cohort, 9 of the 13 cases of bladder cancer and 36 persons with atypical bladder cytology, histology, or pathology were compared with 335 noncases for distributions of different variables. Occupational variables were significant in a multivariate model that controlled for age, cigarette smoking history, and source of drinking water. The estimated odds ratio for the association for bladder cancer and the duration of employment, when controlling of these other variables, is 4.3 (95% CI = 1.8, 10.3). In addition to the occupational factors, age was significant in the multivariate analysis. Other potential risk factors, such as consumption of coffee or artificial sweeteners, use of phenacetin, or decreased use of vitamin A were not found to be significantly different in cases and noncases.

  18. On a FOX hunt: functions of FOX transcriptional regulators in bladder cancer.

    PubMed

    Yamashita, Hironobu; Amponsa, Vasty Osei; Warrick, Joshua I; Zheng, Zongyu; Clark, Peter E; Raman, Jay D; Wu, Xue-Ru; Mendelsohn, Cathy; DeGraff, David J

    2017-02-01

    Genomic and transcriptional studies have identified discrete molecular subtypes of bladder cancer. These observations could be the starting point to identify new treatments. Several members of the forkhead box (FOX) superfamily of transcription factors have been found to be differentially expressed in the different bladder cancer subtypes. In addition, the FOXA protein family are key regulators of embryonic bladder development and patterning. Both experimental and clinical data support a role for FOXA1 and FOXA2 in urothelial carcinoma. FOXA1 is expressed in embryonic and adult urothelium and its expression is altered in urothelial carcinomas and across disparate molecular bladder cancer subtypes. FOXA2 is normally absent from the adult urothelium, but developmental studies identified FOXA2 as a marker of a transient urothelial progenitor cell population during bladder development. Studies also implicate FOXA2 in bladder cancer and several other FOX proteins might be involved in development and/or progression of this disease; for example, FOXA1 and FOXO3A have been associated with clinical patient outcomes. Future studies should investigate to what extent and by which mechanisms FOX proteins might be directly involved in bladder cancer pathogenesis and treatment responses.

  19. Detection of bladder cancer using novel DNA methylation biomarkers in urine sediments

    PubMed Central

    Chung, Woonbok; Bondaruk, Jolanta; Jelinek, Jaroslav; Lotan, Yair; Liang, Shoudan; Czerniak, Bogdan; Issa, Jean-Pierre J.

    2011-01-01

    Background Bladder cancer remains a lethal malignancy that can be cured if detected early. DNA hypermethylation is a common epigenetic abnormality in cancer that may serve as a marker of disease activity. Methods We selected 10 novel candidate genes from the most frequently hypermethylated genes detected by DNA microarray and bisulfite pyrosequencing of bladder cancers and applied them to detect bladder cancer in urine sediments. We analyzed DNA methylation in the candidate genes by quantitative methylation specific real time PCR (qMSP) to detect bladder cancer in urine sediments from 128 bladder cancer patients and 110 age-matched control subjects. Results Based on a multi-gene predictive model, we discovered 6 methylation markers (MYO3A, CA10, SOX11, NKX6-2, PENK and DBC1) as most promising for detecting bladder cancer. A panel of 4 genes (MYO3A, CA10, NKX6-2 and DBC1 or SOX11) had 81 % sensitivity and 97 % specificity, while a panel of 5 genes (MYO3A, CA10, NKX6-2, DBC1 and SOX11 or PENK) had 85 % sensitivity and 95 % specificity for detection of bladder cancer (AUC=0.939). Analyzing the data by cancer invasiveness, detection rate was 47 out of 58 (81 %) in non-muscle invasive tumors (pTa, Tis and pT1) and 62 out of 70 (90 %) in muscle invasive tumors (T2, T3 and T4). Conclusion This biomarker panel analyzed by qMSP may help the early detection of bladder tumors in urine sediments with high accuracy. Impact The panel of biomarker deserves validation in a large well-controlled prospectively collected sample set. PMID:21586619

  20. Case-control study of bladder cancer and water disinfection methods in Colorado.

    PubMed

    McGeehin, M A; Reif, J S; Becher, J C; Mangione, E J

    1993-10-01

    A population-based case-control study of bladder cancer and drinking water disinfection methods was conducted during 1990-1991 in Colorado. Surface water in Colorado has historically been disinfected with chlorine (chlorination) or with a combination of chlorine and ammonia (chloramination). A total of 327 histologically verified bladder cancer cases were frequency matched by age and sex to 261 other-cancer controls. Subjects were interviewed by telephone about residential and water source histories. This information was linked to data from water utility and Colorado Department of Health records to create a drinking water exposure profile. After adjustment for cigarette smoking, tap water and coffee consumption, and medical history factors by logistic regression, years of exposure to chlorinated surface water were significantly associated with risk for bladder cancer (p = 0.0007). The odds ratio for bladder cancer increased for longer durations of exposure to a level of 1.8 (95% confidence interval 1.1-2.9) for more than 30 years of exposure to chlorinated surface water compared with no exposure. The increased bladder cancer risk was similar for males and females and for nonsmokers and smokers. Levels of total trihalomethanes, nitrates, and residual chlorine were not associated with bladder cancer risk after controlling for years of exposure to chlorinated water.

  1. Pioglitazone has a dubious bladder cancer risk but an undoubted cardiovascular benefit.

    PubMed

    Ryder, R E J

    2015-03-01

    On 8 April 2014, a US jury ordered Takeda and Eli Lilly to pay $9 bn in punitive damages after finding that they had concealed the cancer risks associated with pioglitazone. By contrast, on 28 August 2014, the long-awaited outcome of the 10-year Kaiser Permanente Northern California study was announced. That study was specifically designed to investigate whether patients exposed to pioglitazone were at an increased risk of bladder cancer and found no association; thus, at last, the controversial issue has been resolved. A review, in retrospect, of the story of the proposed link between pioglitazone and bladder cancer reveals flaws at every stage. In 2012, a BMJ editorial, in keeping with some other contemporary reports, stated 'it can confidently be assumed that pioglitazone increases the risk of bladder cancer'. Examination of the information which led to such a statement shows that: 1) the pre-clinical findings of bladder cancer in male rats is not indicative of human risk; 2) there is no association between bladder cancer and pioglitazone in randomized controlled trials, once cases that could not plausibly be related to treatment are removed; and 3) the observational studies that have suggested a link have over-extrapolated from the data: pioglitazone-treated patients had more risk factors for bladder cancer than those not treated with pioglitazone. Meanwhile careful study of randomized controlled trials shows evidence of cardiovascular benefit from pioglitazone in Type 2 diabetes, a condition which results, more than anything, in premature cardiovascular death and morbidity.

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

    PubMed Central

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

    2015-01-01

    Purpose: The aim of this study was to investigate occupational risk factors associated with bladder cancer. Materials and Methods: In this case–control study, control group included patients who referred to a specialized clinic in the same city and hospitals where patients had been registered. Data were entered into SPSS software. Odds ratios (OR) were calculated for occupational variables and other characteristics. Then, using logistic regression, the association between cancer and drugs was studied while smoking was controlled. Results: Cigarette smoking, even after quitting, was also associated with bladder cancer (OR = 2.549). Considering the classification of occupations, the OR of working in metal industry in patients was 10.629. Multivariate analysis showed that use of the drug by itself can be a risk factor for bladder cancer. Drug abuse together with the control of smoking increased the risk of bladder cancer by 4.959. Conclusion: According to the findings of this study, contact with metal industries such as welding, and working with tin was found as a risk factor for bladder cancer. In addition, cigarette smoking and opium abuse individually were associated with bladder cancer. PMID:26942139

  3. CD147 and MCT1-potential partners in bladder cancer aggressiveness and cisplatin resistance.

    PubMed

    Afonso, Julieta; Santos, Lúcio L; Miranda-Gonçalves, Vera; Morais, António; Amaro, Teresina; Longatto-Filho, Adhemar; Baltazar, Fátima

    2015-11-01

    The relapsing and progressive nature of bladder tumors, and the heterogeneity in the response to cisplatin-containing regimens, are the major concerns in the care of urothelial bladder carcinoma (UBC) patients. The metabolic adaptations that alter the tumor microenvironment and thus contribute to chemoresistance have been poorly explored in UBC setting. We found significant associations between the immunoexpressions of the microenvironment-related molecules CD147, monocarboxylate transporters (MCTs) 1 and 4, CD44 and CAIX in tumor tissue sections from 114 UBC patients. The presence of MCT1 and/or MCT4 expressions was significantly associated with unfavorable clinicopathological parameters. The incidence of CD147 positive staining significantly increased with advancing stage, grade and type of lesion, and occurrence of lymphovascular invasion. Similar associations were observed when considering the concurrent expression of CD147 and MCT1. This expression profile lowered significantly the 5-year disease-free and overall survival rates. Moreover, when selecting patients who received platinum-based chemotherapy, the prognosis was significantly worse for those with MCT1 and CD147 positive tumors. CD147 specific silencing by small interfering RNAs (siRNAs) in UBC cells was accompanied by a decrease in MCT1 and MCT4 expressions and, importantly, an increase in chemosensitivity to cisplatin. Our results provide novel insights for the involvement of CD147 and MCTs in bladder cancer progression and resistance to cisplatin-based chemotherapy. We consider that the possible cooperative role of CD147 and MCT1 in determining cisplatin resistance should be further explored as a potential theranostics biomarker.

  4. Sinomenine reverses multidrug resistance in bladder cancer cells via P-glycoprotein-dependent and independent manners.

    PubMed

    Chen, Yule; Zhang, Linlin; Lu, Xinlan; Wu, Kaijie; Zeng, Jin; Gao, Yang; Shi, Qi; Wang, Xinyang; Chang, Luke S; He, Dalin

    2014-01-01

    P-Glycoprotein-mediated multidrug resistance is a frequent event during chemotherapy and a key obstacle for bladder cancer therapy. Search for strategies to reverse multidrug resistance is a promising approach to improve the management of bladder cancer. In the present study, we reported a novel P-glycoprotein-mediated multidrug resistant cell model 253J/DOX, which was generated from human bladder cancer 253J cell line. Furthermore, we found that the multidrug resistant phenotype of 253J/DOX cells could be overcome by sinomenine, an alkaloid derived from the stem of Sinomenium acutum. Mechanistically, the chemosensitive effect by sinomenine was mediated by down-regulating P-glycoprotein expression, as well as triggering apoptotic pathways. The chemosensitive effect of sinomenine may make it a prime candidate agent to target bladder cancer.

  5. Nanotechnology in bladder cancer: current state of development and clinical practice.

    PubMed

    Tomlinson, Ben; Lin, Tzu-yin; Dall'Era, Marc; Pan, Chong-Xian

    2015-01-01

    Nanotechnology is being developed for the diagnosis and treatment of both nonmyoinvasive bladder cancer (NMIBC) and invasive bladder cancer. The diagnostic applications of nanotechnology in NMIBC mainly focus on tumor identification during endoscopy to increase complete resection of bladder cancer while nanotechnology to capture malignant cells or their components continues to be developed. The therapeutic applications of nanotechnology in NMIBC are to reformulate biological and cytotoxic agents for intravesical instillation, combine both diagnostic and therapeutic application in one nanoformulation. In invasive and advanced bladder cancer, magnetic resonance imaging with supraparamagnetic iron oxide nanoparticles can improve the sensitivity and specificity in detecting small metastasis to lymph nodes. Nanoformulation of cytotoxic agents can potentially decrease the toxicity while increasing efficacy.

  6. Neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer: which patients benefit?

    PubMed

    Niegisch, Günter; Lorch, Anja; Droller, Michael J; Lavery, Hugh J; Stensland, Kristian D; Albers, Peter

    2013-09-01

    Level I evidence supports neoadjuvant chemotherapy in the treatment of advanced bladder cancer. For the most benefit, it is suggested that neoadjuvant chemotherapy be restricted to patients with clinical T3 disease and/or clinical N+ disease.

  7. Chemoradiation May Help Some Patients with Bladder Cancer Avoid Radical Surgery

    Cancer.gov

    Researchers in the United Kingdom have found that adding chemotherapy to radiation therapy as a treatment for bladder cancer may reduce the risk of a recurrence more than radiation alone, without causing a substantial increase in side effects.

  8. MicroRNA-1280 Inhibits Invasion and Metastasis by Targeting ROCK1 in Bladder Cancer

    PubMed Central

    Majid, Shahana; Dar, Altaf A.; Saini, Sharanjot; Shahryari, Varahram; Arora, Sumit; Zaman, Mohd Saif; Chang, Inik; Yamamura, Soichiro; Chiyomaru, Takeshi; Fukuhara, Shinichiro; Tanaka, Yuichiro; Deng, Guoren; Tabatabai, Z. Laura; Dahiya, Rajvir

    2012-01-01

    MicroRNAs (miRNAs) are non-protein-coding sequences that can function as oncogenes or tumor suppressor genes. This study documents the tumor suppressor role of miR-1280 in bladder cancer. Quantitative real-time PCR and in situ hybridization analyses showed that miR-1280 is significantly down-regulated in bladder cancer cell lines and tumors compared to a non-malignant cell line or normal tissue samples. To decipher the functional significance of miR-1280 in bladder cancer, we ectopically over-expressed miR-1280 in bladder cancer cell lines. Over-expression of miR-1280 had antiproliferative effects and impaired colony formation of bladder cancer cell lines. FACS (fluorescence activated cell sorting) analysis revealed that re-expression of miR-1280 in bladder cancer cells induced G2-M cell cycle arrest and apoptosis. Our results demonstrate that miR-1280 inhibited migration and invasion of bladder cancer cell lines. miR-1280 also attenuated ROCK1 and RhoC protein expression. Luciferase reporter assays demonstrated that oncogene ROCK1 is a direct target of miR-1280 in bladder cancer. This study also indicates that miR-1280 may be of diagnostic and prognostic importance in bladder cancer. For instance, ROC analysis showed that miR-1280 expression can distinguish between malignant and normal bladder cancer cases and Kaplan-Meier analysis revealed that patients with miR-1280 high expression had higher overall survival compared to those with low miR-1280 expression. In conclusion, this is the first study to document that miR-1280 functions as a tumor suppressor by targeting oncogene ROCK1 to invasion/migration and metastasis. Various compounds are currently being used as ROCK1 inhibitors; therefore restoration of tumor suppressor miR-1280 might be therapeutically useful either alone or in combination with these compounds in the treatment of bladder cancer. PMID:23056431

  9. MicroRNA-1280 inhibits invasion and metastasis by targeting ROCK1 in bladder cancer.

    PubMed

    Majid, Shahana; Dar, Altaf A; Saini, Sharanjot; Shahryari, Varahram; Arora, Sumit; Zaman, Mohd Saif; Chang, Inik; Yamamura, Soichiro; Chiyomaru, Takeshi; Fukuhara, Shinichiro; Tanaka, Yuichiro; Deng, Guoren; Tabatabai, Z Laura; Dahiya, Rajvir

    2012-01-01

    MicroRNAs (miRNAs) are non-protein-coding sequences that can function as oncogenes or tumor suppressor genes. This study documents the tumor suppressor role of miR-1280 in bladder cancer. Quantitative real-time PCR and in situ hybridization analyses showed that miR-1280 is significantly down-regulated in bladder cancer cell lines and tumors compared to a non-malignant cell line or normal tissue samples. To decipher the functional significance of miR-1280 in bladder cancer, we ectopically over-expressed miR-1280 in bladder cancer cell lines. Over-expression of miR-1280 had antiproliferative effects and impaired colony formation of bladder cancer cell lines. FACS (fluorescence activated cell sorting) analysis revealed that re-expression of miR-1280 in bladder cancer cells induced G2-M cell cycle arrest and apoptosis. Our results demonstrate that miR-1280 inhibited migration and invasion of bladder cancer cell lines. miR-1280 also attenuated ROCK1 and RhoC protein expression. Luciferase reporter assays demonstrated that oncogene ROCK1 is a direct target of miR-1280 in bladder cancer. This study also indicates that miR-1280 may be of diagnostic and prognostic importance in bladder cancer. For instance, ROC analysis showed that miR-1280 expression can distinguish between malignant and normal bladder cancer cases and Kaplan-Meier analysis revealed that patients with miR-1280 high expression had higher overall survival compared to those with low miR-1280 expression. In conclusion, this is the first study to document that miR-1280 functions as a tumor suppressor by targeting oncogene ROCK1 to invasion/migration and metastasis. Various compounds are currently being used as ROCK1 inhibitors; therefore restoration of tumor suppressor miR-1280 might be therapeutically useful either alone or in combination with these compounds in the treatment of bladder cancer.

  10. Bladder metastasis from primary breast cancer: a case report and literature review

    PubMed Central

    Ghaida, Rami Abou; Ayoub, Hajar; Nasr, Rami; Issa, Ghada

    2013-01-01

    Breast cancer is the most common malignancy in woman. The urinary bladder is an unusual site for metastasis from primary tumors of the breast, especially when it is the only organ involved. We present the case of a female patient with known breast cancer stage T2N3M0 who developed isolated bladder metastasis five years after the primary diagnosis. We reviewed the literature for similar cases and discussed the clinical presentation, pathophysiology, and prognosis of this entity. PMID:24579023

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

    SciTech Connect

    Zheng, Jiajia; Zhu, Xi; Zhang, Jie

    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.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-19

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

  15. Effects of Androgen and Estrogen Receptor Signaling Pathways on Bladder Cancer Initiation and Progression

    PubMed Central

    Godoy, Guilherme; Gakis, Georgios; Smith, Carolyn L.; Fahmy, Omar

    2016-01-01

    Epidemiologic studies have long demonstrated clear differences in incidence and progression of bladder cancer between genders suggesting that the mechanisms of development and progression in these tumors have a strong association with steroid hormonal pathways. Such observations led to preclinical studies investigating the role of androgen and estrogen receptors, as well as their cognate hormones in bladder cancer initiation and progression. Using various in vitro cell line assays and in vivo mouse models, studies have elucidated different mechanisms and signaling pathways through which these steroid receptors may participate in this disease. More recently, RNA expression data from multiple studies revealed a luminal subtype of bladder cancer that exhibited an estrogen receptor signaling pathway, making it a strong candidate for further consideration of targeted therapies in the future. Despite the promising preclinical data demonstrating potential roles for both antiandrogen and antiestrogen strategies targeting these pathways in different stages of bladder cancer, only two clinical trials are currently active and accruing patients for such clinical studies. Targeted therapies in bladder cancer are a large unmet need and have the potential to change treatment paradigms and improve oncological outcomes of patients with bladder cancer. PMID:27376135

  16. G-protein-coupled receptor 137 accelerates proliferation of urinary bladder cancer cells in vitro.

    PubMed

    Du, Yiheng; Bi, Wenhuan; Zhang, Fei; Wu, Wenbo; Xia, Shujie; Liu, Haitao

    2015-01-01

    Urinary bladder cancer is a worldwide concern because of its level of incidence and recurrence. To search an effective therapeutic strategy for urinary bladder cancer, it is important to identify proteins involved in tumorigenesis that could serve as potential targets for diagnosis and treatment. G-protein-coupled receptors (GPRs) constitute a large protein family of receptors that sense molecules outside the cell and activate signal transduction pathways and cellular responses inside the cell. GPR137 is a newly discovered human gene encoding orphan GPRs. In this study, we aimed to investigate the physiological role of GPR137 in urinary bladder cancer. The effect of GPR137 on cell growth was examined via an RNA interference (RNAi) lentivirus system in two human urinary bladder cancer cell lines BT5637 and T24. Lentivirus-mediated RNAi could specifically suppressed GPR137 expression in vitro, resulting in alleviated cell viability and impaired colony formation, as well as blocks G0/G1 and S phases of the cell cycle. These results suggested GPR137 as an essential player in urinary bladder cancer cell growth, and it may serve as a potential target for gene therapy in the treatment of urinary bladder cancer.

  17. In vivo disruption of an Rb-E2F-Ezh2 signaling loop causes bladder cancer

    PubMed Central

    Dueñas, Marta; García-Escudero, Ramón; Alfaya, Begoña; Villacampa, Felipe; Saiz-Ladera, Cristina; Costa, Clotilde; Oteo, Marta; Duarte, José; Martínez, Victor; Gómez-Rodriguez, Mª José; Martín, Mª Luisa; Fernández, Manoli; Viatour, Patrick; Morcillo, Miguel A; Sage, Julien; Castellano, Daniel; Rodriguez-Peralto, Jose L; de la Rosa, Federico; Paramio, Jesús M

    2014-01-01

    Bladder cancer (BC) is a highly prevalent human disease in which retinoblastoma (Rb) pathway inactivation and epigenetic alterations are common events. However, the connection between these two processes is still poorly understood. Here we show that the in vivo inactivation of all Retinoblastoma (Rb) family genes in the mouse urothelium is sufficient to initiate BC development. The characterization of the mouse tumors revealed multiple molecular features of human BC, including the activation of E2F transcription factor and subsequent Ezh2 expression, and the activation of several signaling pathways previously identified as highly relevant in urothelial tumors. These mice represent a genetically defined model for human high-grade superficial BC. Whole transcriptional characterizations of mouse and human bladder tumors revealed a significant overlap and confirm the predominant role for Ezh2 in the downregulation of gene expression programs. Importantly, the increased tumor recurrence and progression in human superficial BC patients is associated with increased E2F and Ezh2 expression and Ezh2-mediated gene expression repression. Collectively, our studies provide a genetically defined model for human high-grade superficial BC and demonstrate the existence of an Rb-E2F-Ezh2 axis in bladder whose disruption can promote tumor development. PMID:25252918

  18. AB175. Girdin protein is a novel prognosis predictor for patients with non-muscle invasive bladder cancer

    PubMed Central

    Wu, Zhouliang; Hu, Hailong; Zhang, Yu; Zhang, Bo; Zhao, Wenlu; Tian, Dawei; Wu, Changli

    2016-01-01

    Objective This study aimed to determine the expression status of actin-binding protein Girdin in non-muscle invasive bladder cancer (NMIBC) tissues, and to explore the relationships between Girdin expression and the clinicopathological characteristics of bladder carcinoma. Methods This study included 160 patients with NMIBC who underwent surgery from January 2006 to January 2011 at Second Hospital of Tianjin Medical University. The correlations between Girdin expression and the clinicopathological parameters were examined by Chi-square test. Recurrence-free survival (RFS) and progression-free survival (PFS) were analyzed using Kaplan-Meier method. The prognostic significance of Girdin expression was assessed using univariate and multivariate Cox regression analysis models. Results Girdin positivity was more frequently seen in high-grade tumors than in low-grade tumors (P=0.019), and in undifferentiated tumors than in differentiated tumors (P=0.028). In Kaplan-Meier analysis, expression of Girdin was significantly associated with lower RFS (P=0.007) and PFS (P=0.024) rates. The univariate analysis revealed that Girdin expression was a risk factor for both recurrence and progression of NMIBC. Further multivariate analysis identified Girdin as an independent predictor of tumor recurrence [hazard ratio (HR) 2.056, 95% CI, 1.213–3.483, P=0.007]. Conclusions The present study suggests that Girdin is differentially expressed in bladder tumors and may represent an independent predictor of prognosis for patients with NMIBC.

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

    PubMed Central

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

    2014-01-01

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

  20. Pharmacologic down-regulation of EZH2 suppresses bladder cancer in vitro and in vivo

    PubMed Central

    Tang, Shou-Hung; Huang, Hsu-Shan; Wu, Hong-Ui; Tsai, Yi-Ta; Chuang, Mei-Jen; Yu, Cheng-Ping; Huang, Shih-Ming; Sun, Guang-Huan; Chang, Sun-Yran; Hsiao, Pei-Wen; Yu, Dah-Shyong; Cha, Tai-Lung

    2014-01-01

    The polycomb group gene, EZH2, is highly expressed in advanced bladder cancer. Here we demonstrated that down-regulation of EZH2 in tumor tissues after neo-adjuvant chemotherapy correlated with good therapeutic response in advanced bladder cancer. We next developed a small molecule, NSC745885, derived from natural anthraquinone emodin, which down-regulated EZH2 via proteasome-mediated degradation. NSC745885 showed potent selective toxicity against multiple cancer cell lines but not normal cells. NSC745885 treatment overcame multiple-drug resistance and inhibited growth of resistant cancer cells. Over-expression of EZH2 in cancer cells attenuated effects of NSC745885, suggesting that down-regulation of EZH2 was responsible for growth inhibition of NSC745885. NSC745885 also suppressed tumor growth and down-regulated EZH2 in vivo. These results indicate that NSC7455889 suppresses bladder cancer by targeting EZH2. PMID:25431950

  1. Bladder cancer in the elderly patient: challenges and solutions

    PubMed Central

    Guancial, Elizabeth A; Roussel, Breton; Bergsma, Derek P; Bylund, Kevin C; Sahasrabudhe, Deepak; Messing, Edward; Mohile, Supriya G; Fung, Chunkit

    2015-01-01

    Bladder cancer (BC) is an age-associated malignancy with increased prevalence in the elderly population. Elderly patients are a vulnerable population at increased risk for treatment-related toxicity secondary to medical comorbidities and geriatric syndromes. As a result, this population has been historically undertreated and suffers worse disease-specific outcomes than younger patients with BC. Recognition of this disparity has led to efforts to individualize treatment decisions based on functional status rather than chronologic age in an effort to optimize the use of curative therapies for the fit elderly and modify treatments to reduce the risk of toxicity and disease-related morbidity in vulnerable or frail patients. The comprehensive geriatric assessment is a decision framework that helps to balance underlying health considerations and risks of therapy with aggressiveness of the cancer. Development of systemic therapies with increased efficacy against BC and reduced toxicity are eagerly awaited, as are techniques and interventions to reduce the morbidity from surgery and radiation for patients with BC. PMID:26089655

  2. Raman microscopy of bladder cancer cells expressing green fluorescent protein

    NASA Astrophysics Data System (ADS)

    Mandair, Gurjit S.; Han, Amy L.; Keller, Evan T.; Morris, Michael D.

    2016-11-01

    Gene engineering is a commonly used tool in cellular biology to determine changes in function or expression of downstream targets. However, the impact of genetic modulation on biochemical effects is less frequently evaluated. The aim of this study is to use Raman microscopy to assess the biochemical effects of gene silencing on T24 and UMUC-13 bladder cancer cell lines. Cellular biochemical information related to nucleic acid and lipogenic components was obtained from deconvolved Raman spectra. We show that the green fluorescence protein (GFP), the chromophore that served as a fluorescent reporter for gene silencing, could also be detected by Raman microscopy. Only the gene-silenced UMUC-13 cell lines exhibited low-to-moderate GFP fluorescence as determined by fluorescence imaging and Raman spectroscopic studies. Moreover, we show that gene silencing and cell phenotype had a greater effect on nucleic acid and lipogenic components with minimal interference from GFP expression. Gene silencing was also found to perturb cellular protein secondary structure in which the amount of disorderd protein increased at the expense of more ordered protein. Overall, our study identified the spectral signature for cellular GFP expression and elucidated the effects of gene silencing on cancer cell biochemistry and protein secondary structure.

  3. Optical spectroscopy by 5-aminolevulinic acid hexylester induced photodynamic treatment in rat bladder cancer

    NASA Astrophysics Data System (ADS)

    Larsen, Eivind L. P.; Randeberg, Lise L.; Gederaas, Odrun A.; Arum, Carl-Jørgen; Krokan, Hans E.; Hjelme, Dag R.; Svaasand, Lars O.

    2006-02-01

    Photodynamic therapy (PDT) is a treatment modality which has been shown to be effective for both malignant and non-malignant diseases. New photosensitizers such as 5-aminolevulinic acid hexylester (hALA) may increase the efficiency of PDT. Monitoring of the tissue response provides important information for optimizing factors such as drug and light dose for this treatment modality. Optical spectroscopy may be suited for this task. To test the efficacy of hALA induced PDT, a study on rats with a superficial bladder cancer model, in which a bladder cancer cell line (AY-27) is instilled, will be performed. Preliminary studies have included a PDT feasibility study on rats, fluorescence spectroscopy on AY-27 cell suspensions, and optical reflection and fluorescence spectroscopy in rat bladders in vivo. The results from the preliminary studies are promising, and the study on hALA induced PDT treatment of bladder cancer will be continued.

  4. Frequencies of poor metabolizers of cytochrome P450 2C19 in esophagus cancer, stomach cancer, lung cancer and bladder cancer in Chinese population

    PubMed Central

    Shi, Wei-Xing; Chen, Shu-Qing

    2004-01-01

    AIM: To investigate the association between cytochrome P450 2C19 (CYP2C19) gene polymorphism and cancer susceptibility by genotyping of CYP2C19 poor metabolizers (PMs) in cancer patients. METHODS: One hundred and thirty-five cases of esophagus cancer, 148 cases of stomach cancer, 212 cases of lung cancer, 112 cases of bladder cancer and 372 controls were genotyped by allele specific amplification-polymerase chain reaction (ASA-PCR) for CYP2C19 PMs. The frequencies of PMs in cancer groups and control group were compared. RESULTS: The frequencies of PMs of CYP2C19 were 34.1% (46/135) in the group of esophagus cancer patients, 31.8% (47/148) in the stomach cancer patients, 34.4% (73/212) in the group of lung cancer patients, only 4.5% (5/112) in the bladder cancer patients and 14.0% (52/372) in control group. There were statistical differences between the cancer groups and control group (esophagus cancer, χ2 = 25.65, P < 0.005, OR = 3.18, 95%CI = 2.005-5.042; stomach cancer, χ2 = 21.70, P < 0.005, OR = 2.86, 95%CI = 1.820-4.501; lung cancer, χ2 = 33.58, P < 0.005, OR = 3.23, 95%CI = 1.503-6.906; bladder cancer, χ2 = 7.50, P < 0.01, OR = 0.288, 95%CI = 0.112-0.740). CONCLUSION: CYP2C19 PMs have a high incidence of esophagus cancer, stomach cancer and lung cancer, conversely they have a low incidence of bladder cancer. It suggests that CYP2C19 may participate in the activation of procarcinogen of esophagus cancer, stomach cancer and lung cancer, but may involve in the detoxification of carcinogens of bladder cancer. PMID:15222046

  5. Circulating and tumor-infiltrating myeloid cell subsets in patients with bladder cancer.

    PubMed

    Eruslanov, Evgeniy; Neuberger, Molly; Daurkin, Irina; Perrin, George Q; Algood, Chester; Dahm, Philipp; Rosser, Charles; Vieweg, Johannes; Gilbert, Scott M; Kusmartsev, Sergei

    2012-03-01

    Both cancer-related inflammation and tumor-induced immune suppression are associated with expansion of myeloid cell subsets including myeloid-derived suppressor cells. However, little known regarding characteristics of myeloid cells in patients with bladder cancer. In this study, we analyzed myeloid cells from peripheral blood (PBMC) and tumor tissue that were collected from patients with superficial noninvasive and invasive urothelial carcinomas. Our results demonstrate that PBMC from bladder cancer patients contain two major CD11b myeloid cell subsets: granulocyte-type CD15(high) CD33(low) cells and monocyte-type CD15(low) CD33(high) cells. The number of circulating granulocytic but not monocytic myeloid cells in cancer patients was markedly increased when compared to healthy individuals. Both myeloid cell subsets from cancer patients were highly activated and produced substantial amounts of proinflammatory chemokines/cytokines including CCL2, CCL3, CCL4, G-CSF, IL-8 and IL-6. Granulocytic myeloid cells were able to inhibit in vitro T cell proliferation through induction of CD4(+) Foxp3(+) T regulatory cells. Analysis of bladder cancer tissues revealed that tumors were infiltrated with monocyte-macrophage CD11b(+) HLA-DR(+) and granulocytic CD11b(+) CD15(+) HLA-DR(-) myeloid cells. Collectively, this study identifies myeloid cell subsets in patients with bladder cancer. We demonstrate that these highly activated inflammatory myeloid cells represent a source of multiple chemokines/cytokines and may contribute to inflammation and immune dysfunction in bladder cancer.

  6. High sensitivity of an Ha-RAS transgenic model of superficial bladder cancer to metformin is associated with ~ 240-fold higher drug concentration in urine than serum

    PubMed Central

    Liu, Zhongbo; Yokoyama, Noriko N.; Blair, Chris A.; Li, Xuesen; Avizonis, Daina; Wu, Xue-Ru; Uchio, Edward; Youssef, Ramy; McClelland, Michael; Pollak, Michael; Zi, Xiaolin

    2016-01-01

    While pharmacoepidemiologic and laboratory studies have supported the hypothesis that the anti-diabetic drug metformin may be useful in treating or preventing cancer, there is limited evidence to suggest which specific cancer sites may be particularly sensitive. Sensitivity likely is determined both by features of tumor pathophysiology and by pharmacokinetic factors. We used UPII mutant Ha-ras transgenic mice that develop hyperplasia and low-grade, papillary urothelial cell carcinoma to determine if metformin has activity in a model of superficial bladder cancer. Metformin significantly improved survival, reduced urinary tract obstruction, reduced bladder weight (a surrogate for tumor volume) and led to clear activation of AMP α kinase and inhibition of mTOR signaling in neoplastic tissue. We investigated the basis of the unusual sensitivity of this model to metformin, and observed that following oral dosing, urothelium is exposed to drug concentrations via the urine that are ~ 240 fold higher than those in the circulation. In addition, we observed that bladder cancer cell lines (RT4, UMUC-3 and J82) with homozygous deletion of either TSC1 or PTEN are more sensitive to metformin than those (TEU2, TCCSUP and HT1376) with wild-type TSC1 and PTEN genes. Our findings provide a strong rationale for clinical trials of oral metformin in treatment of superficial bladder cancer. PMID:26921394

  7. Genome-wide interaction study of smoking and bladder cancer risk

    PubMed Central

    Figueroa, Jonine D.; Han, Summer S.; Garcia-Closas, Montserrat; Baris, Dalsu; Jacobs, Eric J.; Kogevinas, Manolis; Schwenn, Molly; Malats, Nuria; Johnson, Alison; Purdue, Mark P.; Caporaso, Neil; Landi, Maria Teresa; Prokunina-Olsson, Ludmila; Wang, Zhaoming; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Vineis, Paolo; Siddiq, Afshan; Cortessis, Victoria K.; Kooperberg, Charles; Cussenot, Olivier; Benhamou, Simone; Prescott, Jennifer; Porru, Stefano; Bueno-de-Mesquita, H.Bas; Trichopoulos, Dimitrios; Ljungberg, Börje; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth; Tjønneland, Anne; Brenan, Paul; Chang-Claude, Jenny; Riboli, Elio; Conti, David; Gago-Dominguez, Manuela; Stern, Mariana C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Hohensee, Chancellor; Rodabough, Rebecca; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Chen, Constance; De Vivo, Immaculata; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Lindstrom, Sara; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Karagas, Margaret R.; Schned, Alan; Armenti, Karla R.; Hosain, G.M.Monawar; Haiman, Chris A.; Fraumeni, Joseph F.; Chanock, Stephen J.; Chatterjee, Nilanjan; Rothman, Nathaniel; Silverman, Debra T.

    2014-01-01

    Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study (GWAS) of smoking and bladder cancer risk based on primary scan data from 3002 cases and 4411 controls from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P values < 5 × 10− 5 were evaluated further in an independent dataset of 2422 bladder cancer cases and 5751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial dataset and in the combined dataset, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers [combined odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.20–1.50, P value = 5.18 × 10− 7]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67–0.84, P value = 6.35 × 10− 7). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, whereas the additive interaction analysis identified more loci with associations among smokers—including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene–environment interactions for tobacco and bladder cancer. PMID:24662972

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

    PubMed

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

    2007-01-01

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

  9. Bladder cancer mortality and private well use in New England: An ecological study

    USGS Publications Warehouse

    Ayotte, J.D.; Baris, D.; Cantor, K.P.; Colt, J.; Robinson, G.R.; Lubin, J.H.; Karagas, M.; Hoover, R.N.; Fraumeni, J.F.; Silverman, D.T.

    2006-01-01

    Study objective: To investigate the possible relation between bladder cancer mortality among white men and women and private water use in New England, USA, where rates have been persistently raised and use of private water supplies (wells) common. Design: Ecological study relating age adjusted cancer mortality rates for white men and women during 1985-1999 and proportion of persons using private water supplies in 1970. After regressing mortality rates on population density, Pearson correlation coefficients were computed between residual rates and the proportion of the population using private water supplies, using the state economic area as the unit of calculation. Calculations were conducted within each of 10 US regions. Setting: The 504 state economic areas of the contiguous United States. Participants: Mortality analysis of 11 cancer sites, with the focus on bladder cancer. Main results: After adjusting for the effect of population density, there was a statistically significant positive correlation between residual bladder cancer mortality rates and private water supply use among both men and women in New England (men, r=0.42; women, r=0.48) and New York/New Jersey (men, r=0.49; women, r=0.62). Conclusions: Use of well water from private sources, or a close correlate, may be an explanatory variable for the excess bladder cancer mortality in New England. Analytical studies are underway to clarify the relation between suspected water contaminants, particularly arsenic, and raised bladder cancer rates in northern New England.

  10. Bladder cancer in Taiwan: relationship to trihalomethane concentrations present in drinking-water supplies.

    PubMed

    Chang, Chih-Ching; Ho, Shu-Chen; Wang, Li-Yu; Yang, Chun-Yuh

    2007-10-01

    The objective of this study was to evaluate whether exposure to disinfection by-products (DBP) is associated with bladder cancer. A matched case-control study was used to investigate the relationship between the risk of death from bladder cancer and exposure to total trihalomethanes (TTHM) in drinking water in 65 municipalities in Taiwan. All bladder cancer deaths of the 65 municipalities from 1996 through 2005 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth,and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels in drinking water in study municipalities were collected from the Taiwan Environmental Protection Administration. The municipality of residence for cancer cases and controls was assumed to be the source of the subject's TTHM exposure via drinking water. The adjusted odds ratios for bladder cancer death for those with high TTHM concentrations in their drinking water were 1.8 (1.18-2.74) and 2.11 (1.43-3.11) compared to the lowest group. The results of this study show that there was a significant positive correlation between the concentration of TTHM in drinking water and risk of death from bladder cancer.

  11. Bladder cancer mortality and private well use in New England: an ecological study

    PubMed Central

    Ayotte, Joseph D; Baris, Dalsu; Cantor, Kenneth P; Colt, Joanne; Robinson, Gilpin R; Lubin, Jay H; Karagas, Margaret; Hoover, Robert N; Fraumeni, Joseph F; Silverman, Debra T

    2006-01-01

    Study objective To investigate the possible relation between bladder cancer mortality among white men and women and private water use in New England, USA, where rates have been persistently raised and use of private water supplies (wells) common. Design Ecological study relating age adjusted cancer mortality rates for white men and women during 1985–1999 and proportion of persons using private water supplies in 1970. After regressing mortality rates on population density, Pearson correlation coefficients were computed between residual rates and the proportion of the population using private water supplies, using the state economic area as the unit of calculation. Calculations were conducted within each of 10 US regions. Setting The 504 state economic areas of the contiguous United States. Participants Mortality analysis of 11 cancer sites, with the focus on bladder cancer. Main results After adjusting for the effect of population density, there was a statistically significant positive correlation between residual bladder cancer mortality rates and private water supply use among both men and women in New England (men, r = 0.42; women, r = 0.48) and New York/New Jersey (men, r = 0.49; women, r = 0.62). Conclusions Use of well water from private sources, or a close correlate, may be an explanatory variable for the excess bladder cancer mortality in New England. Analytical studies are underway to clarify the relation between suspected water contaminants, particularly arsenic, and raised bladder cancer rates in northern New England. PMID:16415269

  12. Low-level arsenic exposure is associated with bladder cancer risk and cigarette smoking: a case-control study among men in Tunisia.

    PubMed

    Feki-Tounsi, Molka; Olmedo, Pablo; Gil, Fernando; Khlifi, Rim; Mhiri, Mohamed-Nabil; Rebai, Ahmed; Hamza-Chaffai, Amel

    2013-06-01

    Although exposure to high levels of arsenic is associated with excess bladder cancer risk, lower exposures generally are not. This study represents the first biomonitoring of arsenic exposure in Tunisia and focuses on a possible association with bladder cancer risk. In this context, 124 male bladder cancer cases and 220 controls were recruited and blood samples were analyzed to determine the concentration of As. The study subjects were stratified into median groups based on concentrations of arsenic in their blood. Blood arsenic (B-As) was significantly two to threefold higher in bladder cancer cases than in controls (p<0.05). The arsenic concentrations were significantly higher among both smokers and workers in construction. However, neither drinking water nor seafood was found to be incriminated as exposure sources. The adjusted risk ratios for B-As concentration categories 0.1-0.67 and ≥ 0.67 μg/L were 0.18 (95% CI=0.014-2.95) and 2.44 (95% CI=1.11-5.35), respectively. Arsenic levels were not found to be associated with tumor grade or stage. The considerable risk in the category of highest cumulative exposure argues for an association between bladder cancer risk and low-level arsenic exposure. Future investigations with larger samples and using techniques that allow the distinction of the different arsenic species should better elucidate this association. Furthermore, the modulation of arsenic level according to the histological grade may be of potential to be used as a diagnostic marker of the disease process and its possible relationship etiologically.

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

    PubMed Central

    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

    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 < 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. 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

  14. Effects of the kava chalcone flavokawain A differ in bladder cancer cells with wild-type versus mutant p53.

    PubMed

    Tang, Yaxiong; Simoneau, Anne R; Xie, Jun; Shahandeh, Babbak; Zi, Xiaolin

    2008-11-01

    Flavokawain A is the predominant chalcone from kava extract. We have assessed the mechanisms of flavokawain A's action on cell cycle regulation. In a p53 wild-type, low-grade, and papillary bladder cancer cell line (RT4), flavokawain A increased p21/WAF1 and p27/KIP1, which resulted in a decrease in cyclin-dependent kinase-2 (CDK2) kinase activity and subsequent G(1) arrest. The increase of p21/WAF1 protein corresponded to an increased mRNA level, whereas p27/KIP1 accumulation was associated with the down-regulation of SKP2, which then increased the stability of the p27/KIP1 protein. The accumulation of p21/WAF1 and p27/KIP1 was independent of cell cycle position and thus not a result of the cell cycle arrest. In contrast, flavokawain A induced a G(2)-M arrest in six p53 mutant-type, high-grade bladder cancer cell lines (T24, UMUC3, TCCSUP, 5637, HT1376, and HT1197). Flavokawain A significantly reduced the expression of CDK1-inhibitory kinases, Myt1 and Wee1, and caused cyclin B1 protein accumulation leading to CDK1 activation in T24 cells. Suppression of p53 expression by small interfering RNA in RT4 cells restored Cdc25C expression and down-regulated p21/WAF1 expression, which allowed Cdc25C and CDK1 activation, which then led to a G(2)-M arrest and an enhanced growth-inhibitory effect by flavokawain A. Consistently, flavokawain A also caused a pronounced CDK1 activation and G(2)-M arrest in p53 knockout but not in p53 wild-type HCT116 cells. This selectivity of flavokawain A for inducing a G(2)-M arrest in p53-defective cells deserves further investigation as a new mechanism for the prevention and treatment of bladder cancer.

  15. Effects of the Kava Chalcone Flavokawain A Differ in Bladder Cancer Cells with Wild-type versus Mutant p53

    PubMed Central

    Tang, Yaxiong; Simoneau, Anne R.; Xie, Jun; Shahandeh, Babbak; Zi, Xiaolin

    2010-01-01

    Flavokawain A is the predominant chalcone from kava extract. We have assessed the mechanisms of flavokawain A's action on cell cycle regulation. In a p53 wild-type, low-grade, and papillary bladder cancer cell line (RT4), flavokawain A increased p21/WAF1 and p27/KIP1, which resulted in a decrease in cyclin-dependent kinase-2 (CDK2) kinase activity and subsequent G1 arrest. The increase of p21/WAF1 protein corresponded to an increased mRNA level, whereas p27/KIP1 accumulation was associated with the down-regulation of SKP2 and then increased the stability of the p27/KIP1 protein. The accumulation of p21/WAF1 and p27/KIP1 was independent of cell cycle position and thus not a result of the cell cycle arrest. In contrast, flavokawain A induced a G2-M arrest in six p53 mutant-type, high-grade bladder cancer cell lines (T24, UMUC3, TCCSUP, 5637, HT1376, and HT1197). Flavokawain A significantly reduced the expression of CDK1-inhibitory kinases, Myt1 and Wee1, and caused cyclin B1 protein accumulation leading to CDK1 activation in T24 cells. Suppression of p53 expression by small interfering RNA in RT4 cells restored Cdc25C expression and down-regulated p21/WAF1 expression, which allowed Cdc25C and CDK1 activation and then led to a G2-M arrest and an enhanced growth-inhibitory effect by flavokawain A. Consistently, flavokawain A also caused a pronounced CDK1 activation and G2-M arrest in p53 knockout but not in p53 wild-type HCT116 cells. This selectivity of flavokawain A for inducing a G2-M arrest in p53-defective cells deserves further investigation as a new mechanism for the prevention and treatment of bladder cancer. PMID:19138991

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

    PubMed

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

    2015-12-01

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

  17. The Prognostic Value of Previous Irradiation on Survival of Bladder Cancer Patients

    PubMed Central

    Krughoff, Kevin; Lhungay, Tamara P.; Barqawi, Zuhair; O’Donnell, Colin; Kamat, Ashish; Wilson, Shandra

    2015-01-01

    Abstract Background: Radiation exposure is an established risk factor for bladder cancer, however consensus is lacking on the survival characteristics of bladder cancer patients with a history of radiation therapy (RT). Confounding patient comorbidities and baseline characteristics hinders prior attempts at developing such a consensus. Objective: To compare the survival characteristics of patients with suspected radiation-induced second primary cancer (RISPC) of the bladder to those with de novo bladder cancer, taking into account the patient comorbidities and baseline characteristics predictive of survival. Methods: Retrospective analysis of patients with muscle-invasive (≥T2a) or BCG-refractory stage Tis-T1 urothelial bladder cancer. Patients were excluded if prior RT exposure was used as treatment for bladder cancer or if cause of death was due to post-operative complications. A digit matching propensity score algorithm was used to match patients with prior radiation treatment to those without prior treatment. Cox regression analysis for time until death was performed following creation of the propensity score matched sample. Results: 29 patients with history of RT were matched with two controls each, resulting in a dataset of 87 observations in the event model. Results from the Cox model indicate a significantly increased hazard ratio for death at 2.22 (p = 0.047, 95% CI: 1.015–4.860) given a history of prior radiation therapy. Conclusions: In a small cohort, bladder cancer patients who underwent cystectomy had a significantly higher risk of death in the face of prior pelvic RT. This effect was found to be independent of surgical complications, numerous established patient characteristics and comorbidities traditionally predictive of survival. PMID:27376117

  18. Is the Inverse Association Between Selenium and Bladder Cancer Due to Confounding by Smoking?

    PubMed Central

    Beane Freeman, Laura E.; Karagas, Margaret R.; Baris, Dalsu; Schwenn, Molly; Johnson, Alison T.; Colt, Joanne S.; Jackson, Brian; Hosain, G. M. Monawar; Cantor, Kenneth P.; Silverman, Debra T.

    2015-01-01

    Selenium has been linked to a reduced risk of bladder cancer in some studies. Smoking, a well-established risk factor for bladder cancer, has been associated with lower selenium levels in the body. We investigated the selenium-bladder cancer association in subjects from Maine, New Hampshire, and Vermont in the New England Bladder Cancer Case-Control Study. At interview (2001–2005), participants provided information on a variety of factors, including a comprehensive smoking history, and submitted toenail samples, from which we measured selenium levels. We estimated odds ratios and 95% confidence intervals among 1,058 cases and 1,271 controls using logistic regression. After controlling for smoking, we saw no evidence of an association between selenium levels and bladder cancer (for fourth quartile vs. first quartile, odds ratio (OR) = 0.98, 95% confidence interval (CI): 0.77, 1.25). When results were restricted to regular smokers, there appeared to be an inverse association (OR = 0.76, 95% CI: 0.58, 0.99); however, when pack-years of smoking were considered, this association was attenuated (OR = 0.91, 95% CI: 0.68, 1.20), indicating potential confounding by smoking. Despite some reports of an inverse association between selenium and bladder cancer overall, our results, combined with an in-depth evaluation of other studies, suggested that confounding from smoking intensity or duration could explain this association. Our study highlights the need to carefully evaluate the confounding association of smoking in the selenium-bladder cancer association. PMID:25776013

  19. Is the inverse association between selenium and bladder cancer due to confounding by smoking?

    PubMed

    Beane Freeman, Laura E; Karagas, Margaret R; Baris, Dalsu; Schwenn, Molly; Johnson, Alison T; Colt, Joanne S; Jackson, Brian; Hosain, G M Monawar; Cantor, Kenneth P; Silverman, Debra T

    2015-04-01

    Selenium has been linked to a reduced risk of bladder cancer in some studies. Smoking, a well-established risk factor for bladder cancer, has been associated with lower selenium levels in the body. We investigated the selenium-bladder cancer association in subjects from Maine, New Hampshire, and Vermont in the New England Bladder Cancer Case-Control Study. At interview (2001-2005), participants provided information on a variety of factors, including a comprehensive smoking history, and submitted toenail samples, from which we measured selenium levels. We estimated odds ratios and 95% confidence intervals among 1,058 cases and 1,271 controls using logistic regression. After controlling for smoking, we saw no evidence of an association between selenium levels and bladder cancer (for fourth quartile vs. first quartile, odds ratio (OR) = 0.98, 95% confidence interval (CI): 0.77, 1.25). When results were restricted to regular smokers, there appeared to be an inverse association (OR = 0.76, 95% CI: 0.58, 0.99); however, when pack-years of smoking were considered, this association was attenuated (OR = 0.91, 95% CI: 0.68, 1.20), indicating potential confounding by smoking. Despite some reports of an inverse association between selenium and bladder cancer overall, our results, combined with an in-depth evaluation of other studies, suggested that confounding from smoking intensity or duration could explain this association. Our study highlights the need to carefully evaluate the confounding association of smoking in the selenium-bladder cancer association.

  20. Expression of the VLA beta 1 integrin family in bladder cancer.

    PubMed Central

    Liebert, M.; Washington, R.; Stein, J.; Wedemeyer, G.; Grossman, H. B.

    1994-01-01

    Integrins are a family of transmembrane heterodimers, many of which function as receptors for extracellular matrix molecules and play a role in adherence to and motility on matrix components. Because of these functions, integrins are suspected of participating in metastatic processes. We investigated the expression of beta 1 integrins in human bladder cancer cell lines and tissues. Expression of beta 1 integrins on cultured bladder cancer cell lines was evaluated by flow cytometry, of 8 cell lines tested, alpha 1 was found in 4, alpha 2 and alpha 3 in all 8, alpha 4 in 1, and alpha 5 in 3. These results were in sharp contrast to the expression detected by immunostaining tissues containing normal urothelium and low stage (noninvasive) and high stage (invasive) bladder cancers. All normal urothelial tissues tested expressed alpha 2 and alpha 3 and none expressed alpha 1, alpha 4, or alpha 5. Similarly, a majority (77%) of low stage (noninvasive) bladder cancers stained positively for alpha 3, whereas only 6 of 13 expressed alpha 2 and none expressed alpha 1, alpha 4, or alpha 5. Among invasive bladder cancers, alpha 1 was detected in 7%, alpha 2 in 24%, alpha 3 in 68%, alpha 5 in 10%, and alpha 4 was not found in any samples. These results indicate that integrin expression in cultured human bladder cancer cell lines does not represent expression observed in tissue samples and may reflect adaption to or selection during tissue culture conditions. A progressive loss of alpha 2 expression is seen from normal urothelial cells through invasive bladder cancers. This loss may contribute to an invasive phenotype by a loss of the cell-cell adherence function mediated by the alpha 2 beta 1 and alpha 3 beta 1 integrins. Images Figure 2 Figure 3 PMID:8178925

  1. Specific survivin dual fluorescence resonance energy transfer molecular beacons for detection of human bladder cancer cells

    PubMed Central

    Wang, Zhi-qiang; Zhao, Jun; Zeng, Jin; Wu, Kai-jie; Chen, Yu-le; Wang, Xin-yang; Chang, Luke S; He, Da-lin

    2011-01-01

    Aim: Survivin molecular beacons can be used to detect bladder cancer cells in urine samples non-invasively. The aim of this study is to improve the specificity of detection of bladder cancer cells using survivin dual fluorescence resonance energy transfer molecular beacons (FRET MBs) that have fluorophores forming one donor-acceptor pair. Methods: Survivin-targeting dual fluorescence resonance energy transfer molecular beacons with unique target sequences were designed, which had no overlap with the other genes in the apoptosis inhibitor protein family. Human bladder cancer cell lines 5637, 253J and T24, as well as the exfoliated cells in the urine of healthy adults and patients with bladder cancer were examined. Images of cells were taken using a laser scanning confocal fluorescence microscope. For assays using dual FRET MBs, the excitation wavelength was 488 nm, and the emission detection wavelengths were 520±20 nm and 560±20 nm, respectively. Results: The human bladder cancer cell lines and exfoliated cells in the urine of patients with bladder cancer incubated with the survivin dual FRET MBs exhibited strong fluorescence signals. In contrast, no fluorescence was detected in the survivin-negative human dermal fibroblasts-adult (HDF-a) cells or exfoliated cells in the urine of healthy adults incubated with the survivin dual FRET MBs. Conclusion: The results suggest that the survivin dual FRET MBs may be used as a specific and non-invasive method for early detection and follow-up of patients with bladder cancer. PMID:22019956

  2. Discordance Between Preoperative and Postoperative Bladder Cancer Location: Implications for Partial-Bladder Radiation

    SciTech Connect

    Goldsmith, Benjamin; Tucker, Kai; Conway, Robert Greg; He, Jiwei; Guzzo, Thomas; Bekelman, Justin; Deville, Curtiland; Vapiwala, Neha; Malkowicz, S. Bruce; Christodouleas, John

    2013-03-01

    Purpose: There is strong interest in partial-bladder radiation whether as a boost or definitive therapy to limit long-term toxicity. It is unclear that a standard preoperative examination can accurately identify all sites of disease within the bladder. The purpose of this study was to determine the correlation between preoperative localization of bladder tumors with postoperative findings to facilitate partial-bladder radiation techniques when appropriate. Methods and Materials: We examined patients with clinically staged T1-T4 invasive transitional cell carcinoma (TCC) or TCC with variant histology with no history of radiation or partial cystectomy undergoing radical cystectomy. Patients were scored as “under-detected” if a bladder site was involved with invasive disease (≥T1) at the time of cystectomy, but not identified preoperatively. Patients were additionally scored as “widely under-detected” if they had postoperative lesions that were not identified preoperatively in a given site, nor in any adjacent site. Rates of under-detected and widely under-detected lesions, as well as univariate and multivariate association between clinical variables and under-detection, were evaluated using logistic regression. Results: Among 222 patients, 96% (213/222) had at least 1 area of discordance. Fifty-eight percent of patients were under-detected in at least 1 location, whereas 12% were widely under-detected. Among 24 patients with a single site of disease on preoperative evaluation, 21/24 (88%) had at least 1 under-detected lesion and 14/24 (58%) were widely under-detected. On multivariate analysis, only solitary site of preoperative disease was associated with increased levels of under-detection of invasive disease (OR = 4.161, 95% CI, 1.368-12.657). Conclusion: Our study shows a stark discordance between preoperative and postoperative localization of bladder tumors. From a clinical perspective, incomplete localization of all sites of disease within the bladder

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

    SciTech Connect

    Canyilmaz, Emine; Yavuz, Melek Nur; Serdar, Lasif; Uslu, Gonca Hanedan; Zengin, Ahmet Yasar; Aynaci, Ozlem; Haciislamoglu, Emel; Bahat, Zumrut; Yoney, Adnan

    2014-11-01

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

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

    PubMed Central

    Tomaszewski, Jeffrey J; Smaldone, Marc C

    2010-01-01

    Transitional cell carcinoma (TCC) is the second most common urologic malignancy, and 70% of patients present with superficial or nonmuscle invasive bladder cancer (NMIBC). Intravesical bacillus Calmette-Guerin (BCG) is the most effective agent for preventing disease recurrence, and the only therapy able to inhibit disease progression. However, recurrence rates as high as 30% and significant local and systemic toxicity have led to increased interest in alternative intravesical therapies. In patients refractory or intolerant to BCG, BCG-interferon α2b, gemcitabine, and anthracyclines (doxorubicin, epirubicin, valrubicin) have demonstrated durable clinical responses. Phase I trials investigating alternative cytotoxic agents, such as apaziquone, taxanes (docetaxel, paclitaxel), and suramin are reporting promising data. Novel immunomodulating agents have demonstrated promise as efficacious alternatives in patients refractory to BCG. Optimization of existing chemotherapeutic regimens using hyperthermia, photodynamic therapy, magnetically-targeted carriers, and liposomes remains an area of active investigation. Despite enthusiasm for new intravesical agents, radical cystectomy remains the treatment of choice for patients with NMIBC who have failed intravesical therapy and selected patients with naïve T1 tumors and aggressive features. This report provides a comprehensive review of contemporary intravesical therapy for NMIBC and refractory NMIBC, with an emphasis on emerging agents and novel treatment modalities. PMID:24198616

  5. Metabolism and growth inhibitory activity of cranberry derived flavonoids in bladder cancer cells.

    PubMed

    Prasain, Jeevan K; Rajbhandari, Rajani; Keeton, Adam B; Piazza, Gary A; Barnes, Stephen

    2016-09-14

    In the present study, anti-proliferative activities of cranberry derived flavonoids and some of their in vivo metabolites were evaluated using a panel of human bladder tumor cell lines (RT4, SCABER, and SW-780) and non-tumorigenic immortalized human uroepithelial cells (SV-HUC). Among the compounds tested, quercetin 3-O-glucoside, isorhamnetin (3'-O-methylquercetin), myricetin and quercetin showed strong concentration-dependent cell growth inhibitory activities in bladder cancer cells with IC50 values in a range of 8-92 μM. Furthermore, isorhamnetin and myricetin had very low inhibitory activity against SV-HUC even at very high concentrations (>200 μM) compared to bladder cancer cells, indicating that their cytotoxicity is selective for cancer cells. To determine whether the differential cell growth inhibitory effects of isomeric flavonoids quercetin 3-O-glucoside (active) and hyperoside (quercetin 3-O-galactoside) (inactive) are related to their metabolism by the cancer cells, SW-780 cells were incubated with these compounds and their metabolism was examined by LC-MS/MS. Compared to quercetin 3-O-glucoside, hyperoside undergoes relatively less metabolic biotransformation (methylation, glucuronidation and quinone formation). These data suggest that isorhamnetin and quercetin 3-O-glucoside may be the active forms of quercetin in prevention of bladder cancer in vivo and emphasize the importance of metabolism for the prevention of bladder cancer by diets rich in cranberries.

  6. Association between metabolic syndrome, obesity, diabetes mellitus and oncological outcomes of bladder cancer: a systematic review.

    PubMed

    Cantiello, Francesco; Cicione, Antonio; Salonia, Andrea; Autorino, Riccardo; De Nunzio, Cosimo; Briganti, Alberto; Gandaglia, Giorgio; Dell'Oglio, Paolo; Capogrosso, Paolo; Damiano, Rocco

    2015-01-01

    Metabolic syndrome is a cluster of several metabolic abnormalities, its prevalence is increasing worldwide. To summarize the most recent evidence regarding the relationship between metabolic syndrome, its components and the oncological outcomes in bladder cancer patients, a National Center for Biotechnology Information PubMed search for relevant articles either published or e-published up to March 2014 was carried out by combining the following Patient population, Intervention, Comparison, Outcome terms: metabolic syndrome, obesity, body mass index, hyperglycemia, insulin resistance, diabetes, hypertension, dyslipidemia, bladder cancer, risk, mortality, cancer specific survival, disease recurrence and progression. Metabolic syndrome is a complex, highly prevalent disorder, and central obesity, insulin resistance, dyslipidemia and hypertension are its main components. Published findings would suggest that metabolic syndrome per se might be associated with an increased risk of bladder cancer in male patients, but it did not seem to confer a risk of worse prognosis. Considering the primary components of metabolic syndrome (hypertension, obesity and dyslipidemia), available data are uncertain, and it is no possible to reach a conclusion yet on either a direct or an indirect association with bladder cancer risk and prognosis. Only with regard to type 2 diabetes mellitus, available data would suggest a potential negative correlation. However, as the evaluation of bladder cancer risk and prognosis in patients with metabolic disorders is certainly complex, further studies are urgently required to better assess the actual role of these metabolic disorders.

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

    PubMed Central

    Luong, Richard; Yu, Eun-Jeong; He, Yongfeng; Gonzalgo, Mark L.; Sun, Zijie

    2016-01-01

    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. PMID:26862755

  8. Current preclinical models for the advancement of translational bladder cancer research.

    PubMed

    DeGraff, David J; Robinson, Victoria L; Shah, Jay B; Brandt, William D; Sonpavde, Guru; Kang, Yibin; Liebert, Monica; Wu, Xue-Ru; Taylor, John A

    2013-02-01

    Bladder cancer is a common disease representing the fifth most diagnosed solid tumor in the United States. Despite this, advances in our understanding of the molecular etiology and treatment of bladder cancer have been relatively lacking. This is especially apparent when recent advances in other cancers, such as breast and prostate, are taken into consideration. The field of bladder cancer research is ready and poised for a series of paradigm-shifting discoveries that will greatly impact the way this disease is clinically managed. Future preclinical discoveries with translational potential will require investigators to take full advantage of recent advances in molecular and animal modeling methodologies. We present an overview of current preclinical models and their potential roles in advancing our understanding of this deadly disease and for advancing care.

  9. The route to personalized medicine in bladder cancer: where do we stand?

    PubMed

    Massari, Francesco; Ciccarese, Chiara; Santoni, Matteo; Brunelli, Matteo; Conti, Alessandro; Modena, Alessandra; Montironi, Rodolfo; Santini, Daniele; Cheng, Liang; Martignoni, Guido; Cascinu, Stefano; Tortora, Giampaolo

    2015-09-01

    Recent advances in molecular biology and drug design have described novel targets in bladder cancer. EGFR, fibroblast growth factor receptor (FGFR), VEGFR, phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, PD-1, cyclooxygenase 2 (COX-2), Aurora kinase A, and miRNA are just examples of these opening frontiers. In addition, epithelial to mesenchymal transition (EMT) and cancer stem cells (CSCs) are promising candidates for future therapeutic approaches. Novel agents, combination, and sequences are emerging from the 747 clinical studies presently in course in bladder cancer to optimize patient outcomes. This report describes the emerging targets and provides an update on ongoing phase I, II, and III trials and preliminary results on targeted agents, used alone, in sequences, or in combination for patients with bladder cancer.

  10. Therapeutic opportunities in the intrinsic subtypes of muscle-invasive bladder cancer.

    PubMed

    McConkey, David J; Choi, Woonyoung; Ochoa, Andrea; Siefker-Radtke, Arlene; Czerniak, Bogdan; Dinney, Colin P N

    2015-04-01

    Recent studies revealed that muscle-invasive bladder cancers segregate into intrinsic basal and luminal subtypes that are similar to those described for breast cancer. Each subtype is enriched with potentially clinically actionable genomic alterations and epigenetic signatures; there are associations between tumor subtype and sensitivity to conventional cisplatin-based chemotherapy. The authors review biological and clinical characteristics of the intrinsic subtypes and describe their implications for the development of conventional and targeted agents. The role that tumor plasticity seems to play in basal and luminal bladder cancer biology and its potential effects on the development of therapeutic resistance is also discussed.

  11. Artesunate Induces Apoptosis of Bladder Cancer Cells by miR-16 Regulation of COX-2 Expression

    PubMed Central

    Zuo, Wei; Wang, Zhen-Zhong; Xue, Jun

    2014-01-01

    Bladder cancer is the most common malignant tumor of the urinary tract and remains one of the major causes of cancer death worldwide. In this study, we investigated the effect and mechanism of Artesunate (ART), a traditional Chinese medicine, on inducing apoptosis of human bladder cancer cells. In vivo antitumor activity was investigated in bladder cancer in rat by subcutaneous injection of different concentration of ART. The effect of ART on growth inhibition and apoptosis of bladder cancer cells was evaluated using dimethylthiazoly-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis, respectively. Cyclooxygenase-2 (COX-2) and miR-16 expression levels were determined with real-time PCR. The concentrations of prostaglandin E2 (PGE2) in the supernatants of bladder cancer cells were measured with an ELISA kit. The miR-16 inhibitor or mimic were transfected into cells to up- or down-regulate miR-16 expression. ART efficiently inhibited orthotopic tumor growth in the bladder cancer rat, which is accompanied with an increase of miR-16 expression and a decrease of COX-2 expression. In vitro, ART could induce cytotoxicity and apoptosis in bladder cancer cells, but presented a much lighter toxicity effect against normal human urothelial cells. ART significantly increased miR-16 expression and decreased the expression of COX-2 and the production of PGE2. More importantly, down-regulation of miR-16 expression could reverse the effect of ART on apoptosis and COX-2 expression in bladder cells. Moreover, exogenous PGE2 could inhibit apoptosis of bladder cancer cells treated with ART. In conclusion, ART can elicit an anti-tumor effect against bladder cancer by up-regulation of miR-16 expression, which resulted in the decrease of COX-2 expression and PGE2 production. Hence, ART might be an effective drug for the treatment of bladder cancer. PMID:25196524

  12. MicroRNA-23b functions as a tumor suppressor by regulating Zeb1 in bladder cancer.

    PubMed

    Majid, Shahana; Dar, Altaf A; Saini, Sharanjot; Deng, Guoren; Chang, Inik; Greene, Kirsten; Tanaka, Yuichiro; Dahiya, Rajvir; Yamamura, Soichiro

    2013-01-01

    MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by targeted repression of transcription and translation. In this study we show that miRNA-23b (miR-23b) acts as a tumor suppressor in bladder cancer. Quantitative real-time PCR analysis showed that miR-23b is significantly down-regulated in bladder cancer cell lines and tumor tissues compared to non-malignant cells and normal tissue samples. We also demonstrate that miR-23b expression has a potential to be diagnostic and prognostic biomarker in bladder cancer. High miR-23b expression is positively correlated with higher overall survival of bladder cancer patients as revealed by Kaplan-Meier analysis. ROC analysis showed that miR-23b expression can distinguish between normal and bladder cancer tissues. Further we elucidated the biological significance of miR-23b in bladder cancer. Over-expression of miR-23b in bladder cancer cells inhibited cell proliferation and impaired colony formation. Fluorescence activated cell sorting (FACS) analysis revealed that re-expression of miR-23b in bladder cancer cells induced G0/G1 cell cycle arrest and apoptosis while inhibiting cell migration and invasion. Luciferase reporter assays demonstrated that Zeb1, a crucial regulator of epithelial-to-mesenchymal transition (EMT), is a direct target of miR-23b in bladder cancer. These results show that loss of miR-23b confers a proliferative advantage and promotes bladder cancer cell migration and invasion. Furthermore, re-expression of miR-23b may be a beneficial therapeutic strategy for the treatment of human bladder cancer.

  13. MicroRNA-23b Functions as a Tumor Suppressor by Regulating Zeb1 in Bladder Cancer

    PubMed Central

    Majid, Shahana; Dar, Altaf A.; Saini, Sharanjot; Deng, Guoren; Chang, Inik; Greene, Kirsten; Tanaka, Yuichiro; Dahiya, Rajvir; Yamamura, Soichiro

    2013-01-01

    MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by targeted repression of transcription and translation. In this study we show that miRNA-23b (miR-23b) acts as a tumor suppressor in bladder cancer. Quantitative real-time PCR analysis showed that miR-23b is significantly down-regulated in bladder cancer cell lines and tumor tissues compared to non-malignant cells and normal tissue samples. We also demonstrate that miR-23b expression has a potential to be diagnostic and prognostic biomarker in bladder cancer. High miR-23b expression is positively correlated with higher overall survival of bladder cancer patients as revealed by Kaplan-Meier analysis. ROC analysis showed that miR-23b expression can distinguish between normal and bladder cancer tissues. Further we elucidated the biological significance of miR-23b in bladder cancer. Over-expression of miR-23b in bladder cancer cells inhibited cell proliferation and impaired colony formation. Fluorescence activated cell sorting (FACS) analysis revealed that re-expression of miR-23b in bladder cancer cells induced G0/G1 cell cycle arrest and apoptosis while inhibiting cell migration and invasion. Luciferase reporter assays demonstrated that Zeb1, a crucial regulator of epithelial-to-mesenchymal transition (EMT), is a direct target of miR-23b in bladder cancer. These results show that loss of miR-23b confers a proliferative advantage and promotes bladder cancer cell migration and invasion. Furthermore, re-expression of miR-23b may be a beneficial therapeutic strategy for the treatment of human bladder cancer. PMID:23844063

  14. Novel Neoadjuvant Therapy Paradigms for Bladder Cancer: Results from the National Cancer Center Institute Forum

    PubMed Central

    Dinney, Colin P.N.; Hansel, Donna; McConkey, David; Shipley, William; Hagan, Michael; Dreicer, Robert; Lerner, Seth; Czerniak, Bogdan; Waldman, Fred; Groshen, Susan; True, Lawrence D.; Petricoin, Emanuel; Theodorescu, Dan; Hruszkewycz, Andrew; Bajorin, Dean

    2014-01-01

    Although bladder cancer (BC) is a significant health threat to the US population, integrated clinical and laboratory investigations of this disease lag behind those of other types of cancer. Advances in BC are especially challenged due in part to a general decreased level of funding over the past 5 years. It is ironic that despite the awareness that BC is the 5th most commonly diagnosed solid malignancy in the United States, and one of the most costly to treat, funding for this organ site lags far behind that of other less common malignancies. Moreover, BC offers several unique opportunities for translational research that make it an ideal candidate for investigation. One distinct advantage over other solid tumor sites is that urine and tissue are readily available for translational studies that can direct the development of novel therapy for this disease. The NCI sponsored “Novel Neoadjuvant Therapy for Bladder Cancer” forum held in brought leading clinical and laboratory-based scientists together with the advocacy community to lay the groundwork for collaborative discovery and translation. The goal of the meeting was to bridge the gaps in translational science and develop the concepts for two novel biomarker-driven clinical trials, one in the neoadjuvant presurgical setting and the other in the setting of bladder preservation with chemoradiation. The meeting provided a unique opportunity to launch a collective effort to establish molecular-based therapy for UC. Herein, we summarize the proceedings of this meeting, and the future plans resulting from this forum. PMID:25443274

  15. Polymorphic enzymes, urinary bladder cancer risk, and structural change in the local industry.

    PubMed

    Ovsiannikov, Daniel; Selinski, Silvia; Lehmann, Marie-Louise; Blaszkewicz, Meinolf; Moormann, Oliver; Haenel, Matthias W; Hengstler, Jan G; Golka, Klaus

    2012-01-01

    In the 1990s, an uncommonly high percentage of glutathione S-transferase M1 (GSTM1) negative bladder cancer cases (70%) was reported in the greater Dortmund area. The question arose as to whether this uncommonly high percentage of GSTM1 negative bladder cancer cases was due to environmental and/or occupational exposure decades ago. Thus, 15 years later, another study on bladder cancer was performed in the same area after the coal, iron, and steel industries had finally closed in the 1990s. In total 196 bladder cancer patients from the St.-Josefs-Hospital Dortmund-Hörde and 235 controls with benign urological diseases were assessed by questionnaire and genotyped for GSTM1, glutathione S-transferase T1 (GSTT1), and the N-acetyltransferase 2 (NAT2) tag SNP rs1495741. The frequency of the GSTM1 negative genotype was 52% in bladder cancer cases and thus lower compared to a previous study performed from 1992 to 1995 in the same area (70%). NAT2 genotypes were distributed equally among cases and controls (63% slow acetylators). Fewer GSTT1 negative genotypes were present in cases (17%) than in controls (20%).

  16. Urothelial cancer stem cells and epithelial plasticity: current concepts and therapeutic implications in bladder cancer.

    PubMed

    Garg, Minal

    2015-12-01

    Urothelial carcinoma is a highly heterogeneous disease that develops along two distinct biological tracks as evident by candidate gene analysis and genome-wide screening and therefore, offers different challenges for clinical management. Tumors representing the truly distinct molecular entities express molecular markers characteristic of a developmental process and a major mechanism of cancer metastasis, known as epithelial-to-mesenchymal transition (EMT). Recently identified subset of cells known as urothelial cancer stem cells (UroCSCs) in urothelial cell carcinoma (UCC) have self-renewal properties, ability to generate cellular tumor heterogeneity via differentiation and are ultimately responsible for tumor growth and viability. In this review paper, PubMed and Google Scholar electronic databases were searched for original research papers and review articles to extract relevant information on the molecular mechanisms delineating the relationship between EMT and cancer stemness and their clinical implications for different subsets of urothelial cell carcinomas. Experimental and clinical studies over the past few years in bladder cancer cell lines and tumor tissues of different cancer subtypes provide evidences and new insights for mechanistic complexity for induction of EMT, tumorigenicity, and cancer stemness in malignant transformation of urothelial cell carcinomas. Differentiation and elimination therapies targeting EMT-cancer stemness pathway have been proposed as cynosure in the molecular biology of urothelial cell carcinomas and could prove to be clinically beneficial in an ability to reverse the EMT phenotype of tumor cells, suppress the properties of UroCSCs, inhibit bladder cancer progression and tumor relapse, and provide rationale in the treatment and clinical management of urothelial cancer.

  17. MicroRNA-490-5p inhibits proliferation of bladder cancer by targeting c-Fos

    SciTech Connect

    Li, Shiqi; Xu, Xianglai; Xu, Xin; Hu, Zhenghui; Wu, Jian; Zhu, Yi; Chen, Hong; Mao, Yeqing; Lin, Yiwei; Luo, Jindan; Zheng, Xiangyi; Xie, Liping

    2013-11-29

    Highlights: •We examined the level of miR-490-5p in bladder cancer tissues and three cancer cell lines. •We are the first to show the function of miR-490-5p in bladder cancer. •We demonstrate c-Fos may be a target of miR-490-5p. -- Abstract: MicroRNAs (miRNAs) are non-protein-coding sequences that play a crucial role in tumorigenesis by negatively regulating gene expression. Here, we found that miR-490-5p is down-regulated in human bladder cancer tissue and cell lines compared to normal adjacent tissue and a non-malignant cell line. To better characterize the function of miR-490-5p in bladder cancer, we over-expressed miR-490-5p in bladder cancer cell lines with chemically synthesized mimics. Enforced expression of miR-490-5p in bladder cancer cells significantly inhibited the cell proliferation via G1-phase arrest. Further studies found the decreased c-Fos expression at both mRNA and protein levels and Luciferase reporter assays demonstrated that c-Fos is a direct target of miR-490-5p in bladder cancer. These findings indicate miR-490-5p to be a novel tumor suppressor of bladder cancer cell proliferation through targeting c-Fos.

  18. Exploiting a Molecular Gleason Grade for Prostate Cancer Therapy

    DTIC Science & Technology

    2010-03-01

    Exploiting a Molecular Gleason Grade for Prostate Cancer Therapy PRINCIPAL INVESTIGATOR: Peter S. Nelson, MD...Molecular Gleason Grade for Prostate Cancer Therapy 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-07-1-0149 5c. PROGRAM ELEMENT... levels of cognate serum proteins. #3 Write final report. (Note the original Aim 3 involving animal studies of altering prostate cancer grade

  19. Trace metal quantification in bladder biopsies from tumoral lesions of Tunisian cancer and controls subjects.

    PubMed

    Feki-Tounsi, Molka; Olmedo, Pablo; Gil, Fernando; Mhiri, Mohamed-Nabil; Rebai, Ahmed; Hamza-Chaffai, Amel

    2014-10-01

    The incidence of bladder tumors has been dramatically increasing since the 1970s, possibly as a consequence of ongoing environmental pollution. Previous studies have provided some evidence of an association between cancer and exposure to carcinogenic metals. In order to examine the association between levels of toxic metals in patients with bladder tumors and controls, the amounts of arsenic, cadmium, chromium, and nickel were measured in tumoral lesions and adjacent normal part of the bladder mucosa excised for carcinoma and compared with those in the bladder mucosa of volunteer subjects operated for non-neoplastic diseases. The quantification of metals in tissue was assessed by atomic absorption spectroscopy. In tumoral tissues of the excised bladder mucosa, content of Cr and Ni was significantly low compared to that of adjacent normal tissues and control tissues while that of As and Cd in normal tissues adjacent to the tumor were significantly elevated compared to controls. Though the sample size was small, the present study shows that concentrations of metals such as Cd, Cr, As, and Ni in bladder tissue may be used as a biomarker of exposure. On the basis of the results obtained in this study, high amounts of As and Cd in adjacent normal parts of the bladders with carcinomas compared to controls would strongly suggest possible, individual or synergistic, effects of these pollutants on enzymatic systems, priming an oncogenic pathway.

  20. Intrinsic basal and luminal subtypes of muscle-invasive bladder cancer.

    PubMed

    Choi, Woonyoung; Czerniak, Bogdan; Ochoa, Andrea; Su, Xiaoping; Siefker-Radtke, Arlene; Dinney, Colin; McConkey, David J

    2014-07-01

    Whole-genome analyses have revealed that muscle-invasive bladder cancers (MIBCs) are heterogeneous and can be grouped into basal and luminal subtypes that are highly reminiscent of those found in breast cancer. Basal MIBCs are enriched with squamous and sarcomatoid features and are associated with advanced stage and metastatic disease at presentation. Like basal breast cancers, basal bladder tumours contain a claudin-low subtype that is enriched with biomarkers characteristic of epithelial-to-mesenchymal transition. The stem cell transcription factor ΔNp63α controls basal MIBC gene expression, just as it does in basal breast cancers. Luminal MIBCs are enriched with activating FGFR3 and ERBB3 mutations and ERBB2 amplifications, and their gene expression profiles are controlled by peroxisome proliferator activator receptor γ (PPARγ) and possibly also by oestrogen receptor activation. Luminal bladder cancers can be further subdivided into two subtypes, p53-like and luminal, which can be distinguished from one another by different levels of biomarkers that are characteristic of stromal infiltration, cell cycle progression, and proliferation. Importantly, basal bladder cancers are intrinsically aggressive, but are highly sensitive to cisplatin-based combination chemotherapy. Although the luminal subtypes are not as intrinsically aggressive as basal cancers, p53-like tumours are resistant to chemotherapy and might, therefore, represent a problem for treated patients.

  1. Lower Urinary Tract Symptoms and Risk of Bladder Cancer in Men: Results from the Health Professionals Follow-Up Study

    PubMed Central

    Zhou, Jiachen; Kelsey, Karl T.; Smith, Scott; Giovannucci, Edward; Michaud, Dominique S.

    2015-01-01

    Objectives To understand the association between Lower urinary tract symptoms (LUTS) and risk of bladder cancer in a large men's cohort. Methods Using data from the Health Professionals Follow-up Study, we examined risk of bladder cancer in relation to severity of LUTS among 30,183 men. During the follow-up period from 1996 until 2010, 476 newly diagnosed cases of bladder cancer occurred. Cox proportional hazards regression was used to adjust for potential confounders. Results Among men with severe LUTS, risk of bladder cancer was 64% higher (relative risk (RR): 1.64, 95% confidence interval (CI): 0.87, 3.08) compared with men who reported no LUTS. Subjects with both voiding and storage dysfunction had a significantly higher risk of bladder cancer (RR: 1.60, 95% confidence interval: 1.00, 2.56). Among individual urinary symptoms, urinary hesitancy was strongly associated with bladder cancer; those who experienced urinary hesitancy at least 50% of the time had more than twice the risk of bladder cancer (RR: 2.21, 95% CI: 1.29, 3.78). Conclusions Our findings suggest that LUTS, especially urinary hesitancy, are associated with the development of bladder cancer in men. PMID:25863833

  2. UBE2T silencing suppresses proliferation and induces cell cycle arrest and apoptosis in bladder cancer cells

    PubMed Central

    Gong, Yan Qing; Peng, Ding; Ning, Xiang Hui; Yang, Xin Yu; Li, Xue Song; Zhou, Li Qun; Guo, Ying Lu

    2016-01-01

    Ubiquitin-conjugating enzyme E2T (UBE2T), a member of the ubiquitin-conjugating E2 family in the ubiquitin-proteasome pathway, has been reported to be overexpressed in certain tumor types and to have an important role in the Fanconi anemia pathway. In the present study, the expression of UBE2T and its association with bladder cancer were investigated; to the best of our knowledge, this has not been reported previously. Immunohistochemistry and western blot analysis demonstrated that UBE2T was significantly upregulated in bladder cancer tissues and cell lines compared with adjacent normal bladder tissues and a normal human urinary tract epithelial cell line, respectively. UBE2T was detectable in the nuclei and cytoplasm of cancer cells, exhibiting stronger expression in the nuclei. A UBE2T-siRNA-expressing lentivirus was constructed and used to infect human bladder cancer 5637 cells, in order to examine the role of UBE2T in bladder cancer cell growth in vitro. The knockdown of UBE2T significantly decreased bladder cancer cell proliferation and colony formation. Furthermore, UBE2T silencing induced cell cycle arrest at G2/M phase and increased cell apoptosis. Therefore, UBE2T serves an important role in the growth of bladder cancer cells, and may be considered as a potential biomarker and therapeutic target for bladder cancer. PMID:28101210

  3. Urinary oncofetal ED-A fibronectin correlates with poor prognosis in patients with bladder cancer.

    PubMed

    Arnold, Shanna A; Loomans, Holli A; Ketova, Tatiana; Andl, Claudia D; Clark, Peter E; Zijlstra, Andries

    2016-01-01

    The extracellular matrix protein fibronectin (FN) contributes to the structural integrity of tissues as well as the adhesive and migratory functions of cells. While FN is abundantly expressed in adult tissues, the expression of several alternatively spliced FN isoforms is restricted to embryonic development, tissue remodeling and cancer. These FN isoforms, designated ED-A and ED-B, are frequently expressed by cancer cells, tumor-associated fibroblasts and newly forming blood vessels. Using a highly sensitive collagen-based indirect ELISA, we evaluated the correlation of urinary ED-A and ED-B at time of cystectomy with overall survival in patients with high-grade bladder cancer (BCa). Detectable levels of total FN as well as ED-A and ED-B were found in urine from 85, 73 and 51 % of BCa patients, respectively. The presence of urinary ED-A was a significant independent predictor of 2-year overall survival (OS) after adjusting for age, tumor stage, lymph node stage, and urinary creatinine by multivariable Logistic Regression (p = 0.029, OR = 4.26, 95 % CI 1.16-15.71) and improved accuracy by 3.6 %. Furthermore, detection of ED-A in the urine was a significant discriminator of survival specifically in BCa patients with negative lymph node status (Log-Rank, p = 0.006; HR = 5.78, 95 % CI 1.39-24.13). Lastly, multivariable Cox proportional hazards analysis revealed that urinary ED-A was an independent prognostic indicator of 5-year OS rate for patients with BCa (p = 0.04, HR = 2.20, 95 % CI 1.04-4.69). Together, these data suggest that cancer-derived, alternatively spliced FN isoforms can act as prognostic indicators and that additional studies are warranted to assess the clinical utility of ED-A in BCa.

  4. Profilin 1 is a Potential Biomarker for Bladder Cancer Aggressiveness*

    PubMed Central

    Zoidakis, Jerome; Makridakis, Manousos; Zerefos, Panagiotis G.; Bitsika, Vasiliki; Esteban, Sergio; Frantzi, Maria; Stravodimos, Konstantinos; Anagnou, Nikolaos P.; Roubelakis, Maria G.; Sanchez-Carbayo, Marta; Vlahou, Antonia

    2012-01-01

    Of the most important clinical needs for bladder cancer (BC) management is the identification of biomarkers for disease aggressiveness. Urine is a “gold mine” for biomarker discovery, nevertheless, with multiple proteins being in low amounts, urine proteomics becomes challenging. In the present study we applied a fractionation strategy of urinary proteins based on the use of immobilized metal affinity chromatography for the discovery of biomarkers for aggressive BC. Urine samples from patients with non invasive (two pools) and invasive (two pools) BC were subjected to immobilized metal affinity chromatography fractionation and eluted proteins analyzed by 1D-SDS-PAGE, band excision and liquid chromatography tandem MS. Among the identified proteins, multiple corresponded to proteins with affinity for metals and/or reported to be phosphorylated and included proteins with demonstrated association with BC such as MMP9, fibrinogen forms, and clusterin. In agreement to the immobilized metal affinity chromatography results, aminopeptidase N, profilin 1, and myeloblastin were further found to be differentially expressed in urine from patients with invasive compared with non invasive BC and benign controls, by Western blot or Elisa analysis, nevertheless exhibiting high interindividual variability. By tissue microarray analysis, profilin 1 was found to have a marked decrease of expression in the epithelial cells of the invasive (T2+) versus high risk non invasive (T1G3) tumors with occasional expression in stroma; importantly, this pattern strongly correlated with poor prognosis and increased mortality. The functional relevance of profilin 1 was investigated in the T24 BC cells where blockage of the protein by the use of antibodies resulted in decreased cell motility with concomitant decrease in actin polymerization. Collectively, our study involves the application of a fractionation method of urinary proteins and as one main result of this analysis reveals the

  5. Validation of the diagnostic utility of urinary midkine for the detection of bladder cancer.

    PubMed

    Vu Van, Dana; Heberling, Ulrike; Wirth, Manfred P; Fuessel, Susanne

    2016-11-01

    As it has been demonstrated previously that midkine (also known as neurite growth-promoting factor 2) protein levels in urine of bladder cancer (BCa) patients are increased compared to healthy controls, the present study validated the diagnostic utility of midkine in an independent patient cohort and compared the observed values with voided urine cytology (VUC), which is the current reference standard for non-invasive diagnosis of BCa. Voided urine samples were prospectively collected from 92 BCa patients and 70 control subjects. Protein levels of midkine were assessed using a commercially available enzyme-linked immunosorbent assay and normalized to urinary creatinine. The diagnostic performance of urinary midkine was evaluated by receiver operating characteristic curves. The best combinations of sensitivities and specificities were determined by Youden's Index. Midkine concentrations were significantly elevated in urine samples from BCa patients compared to controls (P<0.001; Mann-Whitney U Test). The level of midkine was associated with disease progression, with the highest concentrations in urine specimens of patients with pT1 and ≥pT2a, as well as high-grade tumors (P<0.001; Mann-Whitney U test). Sensitivities of urinary midkine and VUC were 69.7 and 87.6%, respectively. The corresponding specificities for midkine and VUC were 77.9 and 87.7%, respectively. The combined use of VUC and midkine improved the sensitivity to 93.3%, but reduced the specificity to 66.2%. Despite its reduced discriminatory power for low-grade and low-stage BCa, urinary midkine can be utilized for the identification of high-grade pT1 and ≥pT2a tumors. This means that midkine may potentially be suitable for the identification of patients with high risk BCa.

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

    PubMed Central

    Parada, Belmiro; Reis, Flávio; Cerejo, Raquel; Garrido, Patrícia; Sereno, José; Xavier-Cunha, Maria; Neto, Paula; Mota, Alfredo; Figueiredo, Arnaldo; Teixeira, Frederico

    2013-01-01

    Omega-3 (ω-3) fatty acids have been tested on prevention and treatment of several cancer types, but the efficacy on “in vivo” bladder cancer has not been analyzed yet. This study aimed at evaluating the chemopreventive efficacy of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) mixture in an animal model of bladder cancer. Forty-four male Wistar rats were divided into 4 groups during a 20-week protocol: control; carcinogen—N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN); ω-3 (DHA + EPA); and ω-3 + BBN. BBN and ω-3 were given during the initial 8 weeks. At week 20 blood and bladder were collected and checked for the presence of urothelium lesions and tumors, markers of inflammation, proliferation, and redox status. Incidence of bladder carcinoma was, control (0%), ω-3 (0%), BBN (65%), and ω-3 + BBN (62.5%). The ω-3 + BBN group had no infiltrative tumors or carcinoma in situ, and tumor volume was significantly reduced compared to the BBN (0.9 ± 0.1 mm3 versus 112.5 ± 6.4 mm3). Also, it showed a reduced MDA/TAS ratio and BBN-induced serum CRP, TGF-β1, and CD31 were prevented. In conclusion, omega-3 fatty acids inhibit the development of premalignant and malignant lesions in a rat model of bladder cancer, which might be due to anti-inflammatory, antioxidant, anti-proliferative, and anti-angiogenic properties. PMID:23865049

  7. Epidemiological case-control study on the etiology of bladder cancer in Turkey.

    PubMed

    Akdaş, A; Kirkali, Z; Bilir, N

    1990-01-01

    A case-control study of 194 patients with bladder cancer and the same number of age- and sex-matched hospital controls were interviewed to estimate the role of various factors on the etiology of bladder cancer in Turkey. There was a significant difference between the case and control groups on cigarette smoking (p less than 0.001), alcohol intake (p less than 0.001), Turkish coffee consumption (p = 0.01), and artificial sweeteners (p less than 0.05). The risks for alcohol and tobacco users increased in correlation with the duration of exposure. The risk of bladder cancer increased directly with the quantity and frequency of alcohol intake. Alcohol and coffee drinking was found to be a promoting factor when adjusted to smoking habits (p less than 0.05). No statistical comparisons could be made to clarify the risks attributed by occupation and place of residence due to small figures in each group. However, in farmers, there was a significant difference between the cases and controls on the use of artificial fertilizers and insecticides (p less than 0.01). People who were exposed to unspecified chemical substances were more prone to develop bladder cancer (p less than 0.001). We conclude that both personal habits and exogenous carcinogens play a role in the etiology of bladder tumors.

  8. Genome-wide association study identifies multiple loci associated with bladder cancer risk

    PubMed Central

    Figueroa, Jonine D.; Ye, Yuanqing; Siddiq, Afshan; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Prokunina-Olsson, Ludmila; Cortessis, Victoria K.; Kooperberg, Charles; Cussenot, Olivier; Benhamou, Simone; Prescott, Jennifer; Porru, Stefano; Dinney, Colin P.; Malats, Núria; Baris, Dalsu; Purdue, Mark; Jacobs, Eric J.; Albanes, Demetrius; Wang, Zhaoming; Deng, Xiang; Chung, Charles C.; Tang, Wei; Bas Bueno-de-Mesquita, H.; Trichopoulos, Dimitrios; Ljungberg, Börje; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth; Tjønneland, Anne; Brenan, Paul; Chang-Claude, Jenny; Riboli, Elio; Conti, David; Gago-Dominguez, Manuela; Stern, Mariana C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Hohensee, Chancellor; Rodabough, Rebecca; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Chen, Constance; De Vivo, Immaculata; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Lindstrom, Sara; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Kamat, Ashish M.; Lerner, Seth P.; Barton Grossman, H.; Lin, Jie; Gu, Jian; Pu, Xia; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Kogevinas, Manolis; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Schwenn, Molly; Karagas, Margaret R.; Johnson, Alison; Schned, Alan; Armenti, Karla R.; Hosain, G.M.; Andriole, Gerald; Grubb, Robert; Black, Amanda; Ryan Diver, W.; Gapstur, Susan M.; Weinstein, Stephanie J.; Virtamo, Jarmo; Haiman, Chris A.; Landi, Maria T.; Caporaso, Neil; Fraumeni, Joseph F.; Vineis, Paolo; Wu, Xifeng; Silverman, Debra T.; Chanock, Stephen; Rothman, Nathaniel

    2014-01-01

    Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10−5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10−9) and rs907611 on 11p15.5 (P = 4.11 × 10−8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10−7) and rs4510656 on 6p22.3 (P = 6.98 × 10−7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis. PMID:24163127

  9. Nanoparticulation of BCG-CWS for application to bladder cancer therapy.

    PubMed

    Nakamura, Takashi; Fukiage, Masafumi; Higuchi, Megumi; Nakaya, Akihiro; Yano, Ikuya; Miyazaki, Jun; Nishiyama, Hiroyuki; Akaza, Hideyuki; Ito, Toshihiro; Hosokawa, Hiroyuki; Nakayama, Toshinori; Harashima, Hideyoshi

    2014-02-28

    The Mycobacterium bovis Bacille Calmette-Guerin cell wall skeleton (BCG-CWS) could be used to replace live BCG as a bladder cancer drug. However, because BCG-CWS is poorly soluble, has a strong-negative charge, very high molecular weight and heterogeneity in size of tens of μm, it cannot be used in such an application. We report herein on the development of a novel packaging method that permits BCG-CWS to be encapsulated into 166nm-sized lipid particles. The BCG-CWS encapsulated nano particle (CWS-NP) has a high uniformity and can be easily dispersed. Thus, it has the potential for use as a packaging method that would advance the scope of applications of BCG-CWS as a bladder cancer drug. In a functional evaluation, CWS-NP was efficiently taken up by mouse bladder tumor (MBT-2) cells in vitro and inhibited tumor growth in mice bearing MBT-2 tumors. Moreover, intravesically administered CWS-NP showed significant antitumor effects in a rat model with naturally developed bladder cancer. An enhancement in Th1 differentiation by CWS-NP was also confirmed in human T cells. In conclusion, CWS-NP represents a promising delivery system for BCG-CWS for clinical development as a potent bladder cancer drug.

  10. Bladder cancer in Massachusetts related to chlorinated and chloraminated drinking water: a case-control study

    SciTech Connect

    Zierler, S.; Feingold, L.; Danley, R.A.; Craun, G.

    1988-03-01

    Consumers of chlorinated drinking water have a small excess of bladder cancer. Risk may have been underestimated because of confounding and misclassification of exposure status. To address these problems, we undertook a case-control study. Detailed residential histories were obtained by telephone interviews with informants of 614 individuals who died of primarily bladder cancer and 1,074 individuals who died of other causes. Their surface water has been disinfected with chlorine or a combination of chlorine and ammonia (cloramine) since 1938. The mortality ratio for bladder cancer among individuals who resided only in communities supplied with drinking water disinfected with chlorine, relative to individuals who resided only in communities supplied with drinking water disinfected with chloramine, was 1.6 (95% confidence interval = 1.2-2.1), using all controls; when the comparison group was restricted to individuals who died of lymphoma, the mortality odds ratio was 2.7 (95% confidence interval = 1.7-4.3).

  11. Bladder cancer in Massachusetts related to chlorinated and chloraminated drinking water: a case-control study.

    PubMed

    Zierler, S; Feingold, L; Danley, R A; Craun, G

    1988-01-01

    Consumers of chlorinated drinking water have a small excess of bladder cancer. Risk may have been underestimated because of confounding and misclassification of exposure status. To address these problems, we undertook a case-control study. Detailed residential histories were obtained by telephone interviews with informants of 614 individuals who died of primarily bladder cancer and 1,074 individuals who died of other causes. Their surface water has been disinfected with chlorine or a combination of chlorine and ammonia (cloramine) since 1938. The mortality ratio for bladder cancer among individuals who resided only in communities supplied with drinking water disinfected with chlorine, relative to individuals who resided only in communities supplied with drinking water disinfected with chloramine, was 1.6 (95% confidence interval = 1.2-2.1), using all controls; when the comparison group was restricted to individuals who died of lymphoma, the mortality odds ratio was 2.7 (95% confidence interval = 1.7-4.3).

  12. Biscoumarin derivatives: Synthesis, crystal structure, theoretical studies and induced apoptosis activity on bladder urothelial cancer cell

    NASA Astrophysics Data System (ADS)

    Xin, Jia-jia; Li, Jing; Zhang, Zi-dan; Hu, Xing-bin; Li, Ming-kai

    2015-03-01

    In this study, five new biscoumarin derivatives (1-5) were synthesized and compound 4 inhibited the proliferation of the bladder urothelial cells (J82 cell line) obviously after 48 h treatment at different concentration (1, 5 and 10 μmol/L), and J82 cells were predominantly induced to apoptotic cell death after compound 4 treatment. Morphologic changes of bladder urothelial cancer cells were also observed under transmission electron microscopy (TEM) after compound 4 treatment. In addition, compound 4 had much less toxicity to human umbilical vein endothelial cells. To explore the possible anti-cancer mechanism of compound 4, two classical intramolecular Osbnd H⋯O hydrogen bonds (HBs) in their structures and the corresponding HB energies were performed with the density functional theory (DFT) [B3LYP/6-31G∗] method. Anti-bladder cancer activity of compound 4 is possible due to the intramolecular weakest HB energies.

  13. Case-control study of diesel exhaust exposure and bladder cancer

    SciTech Connect

    Wynder, E.L.; Dieck, G.S.; Hall, N.E.L.; Lahti, H.

    1985-08-01

    The relationship between bladder cancer and employment in occupations involving exposure to diesel exhaust was examined using data from a hospital-based case-control study of men aged 20 to 80 years in 18 hospitals in six US cities, from January 1981 to May 1983. In this analysis, 194 cases and 582 controls were compared according to occupation, smoking history, alcohol and coffee consumption, and various demographic variables. No difference was found in the proportion of bladder cancer cases employed in occupations with exposure to diesel exhaust compared to controls. This relationship did not change after taking smoking habits into account. Bladder cancer cases were significantly more likely to be current smokers of cigarettes than were controls.

  14. The Future of Intravesical Drug Delivery for Non-Muscle Invasive Bladder Cancer

    PubMed Central

    Douglass, Laura; Schoenberg, Mark

    2016-01-01

    Despite being the fifth most common cancer in the United States, minimal progress has been made in the treatment of bladder cancer in over a decade. Intravesical instillation of Bacillus Calmette-Guerin (BCG) for the treatment of non-muscle invasive bladder cancer (NMIBC) has been in use for over 30 years and remains the standard treatment in cases of intermediate and high risk disease. Despite the relative success of intravesical BCG, unmet needs in the treatment of NMIBC persist. These challenges include disease recurrence and progression even with treatment with BCG, as well as issues regarding its availability and patient tolerability. The inherent properties of the bladder pose the biggest obstacle to developing effective intravesical treatments for NMIBC. Current research is now focusing on methods to improve the delivery of intravesical therapies. The objective of this review is to discuss novel intravesical drug delivery systems and how they are addressing these challenges in the treatment of NMIBC. PMID:27500196

  15. The role of cyclooxygenase enzymes in the growth of human gall bladder cancer cells.

    PubMed

    Grossman, E M; Longo, W E; Panesar, N; Mazuski, J E; Kaminski, D L

    2000-07-01

    Information suggests that the cyclooxygenase (COX) metabolites, the prostanoids, play a role in gall bladder physiology and disease. Non-steroidal anti-inflammatory drugs which inhibit COX enzymes have been shown in vivo and in vitro to alter the growth patterns of intestinal epithelial cells, and specific COX-2 inhibitors have been shown to decrease mitogenesis in intestinal epithelial cells. The present study was intended to evaluate the effect of specific COX inhibitors on the growth patterns of gall bladder cancer cells. Employing a human gall bladder cancer cell line, mitogenesis, apoptosis and prostaglandin E(2) (PGE(2)) formation were evaluated in response to serum and hepatocyte growth factor and transforming growth factor alpha stimulation in the presence and absence of specific COX-1 and -2 inhibitors. The effect of the mitogens on COX enzyme expression was also evaluated. Serum and the growth factors increased COX enzyme expression and mitogenesis, and decreased apoptosis as evaluated by the percentage of cells that were floating in culture media rather than attached. There was more DNA degradation in floating than in attached cells. The specific COX-2 inhibitor, but not the COX-1 inhibitor, decreased mitogenesis and increased gall bladder cell apoptosis as evaluated by the number of floating versus attached cells and the number of floating cells in the terminal phase of apoptosis or dead. The inhibition of mitogenesis and the increased apoptosis produced by the COX-2 inhibitor was associated with decreased PGE(2) production. The inhibition of replication of gall bladder cancer cells and the increase in apoptosis produced by the selective COX-2 inhibitor suggests that the COX enzymes and the prostanoids may play a role in the development of gall bladder cancer and that the COX-2 inhibitors may have a therapeutic role in the prevention of gall bladder neoplasms.

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

    SciTech Connect

    Weiss, Christian; Krause, Steffen F.; Sauer, Rolf; Roedel, Claus; Roedel, Franz

    2009-08-01

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

  17. Evaluation of the Efficacy of the H. pylori Protein HP-NAP as a Therapeutic Tool for Treatment of Bladder Cancer in an Orthotopic Murine Model.

    PubMed

    Codolo, Gaia; Munari, Fabio; Fassan, Matteo; de Bernard, Marina

    2015-05-29

    Bladder cancer is one of the most common malignancies of the urogenital tract. Intravesical injection of Bacillus Calmette-Guérin (BCG) is the gold standard treatment for the high-grade non-muscle invasive bladder cancer (NMIBC). However, since the treatment-related side effects are relevant, newer biological response modifiers with a better benefit/side effects ratio are needed. The tumour microenvironment can influence both tumour development and therapy efficacy. In order to obtain a good model, it is desirable to implant tumour cells in the organ from which the cancer originates. In this protocol, we describe a method for establishing a tumour in the bladder cavity of female mice and subsequent delivery of therapeutic agents; the latter are exemplified by our use of Helicobacter pylori neutrophil activating protein (HP-NAP). A preliminary chemical burn of the mucosa, followed by the injection of mouse urothelial carcinoma cell line MB49 via urethral catheterization, enables the cells to attach to the bladder mucosa. After a period, required to allow an initial proliferation of the cells, mice are treated with HP-NAP, administrated again via catheterization. The anti-tumour activity of HP-NAP is evaluated comparing the tumour volume, the extent of necrosis and the degree of vascularization between vehicle- and HP-NAP-treated animals.

  18. Metformin and gefitinib cooperate to inhibit bladder cancer growth via both AMPK and EGFR pathways joining at Akt and Erk

    PubMed Central

    Peng, Mei; Huang, Yanjun; Tao, Ting; Peng, Cai-Yun; Su, Qiongli; Xu, Wanjun; Darko, Kwame Oteng; Tao, Xiaojun; Yang, Xiaoping

    2016-01-01

    EGFR is a potential therapeutic target for treating bladder cancer, but has not been approved for clinical use yet. Metformin is a widely used antidiabetic drug and has demonstrated interesting anticancer effects on various cancer models, alone or in combination with chemotherapeutic drugs. The efficacy of gefitinib, a well-known EGFR tyrosine kinase inhibitor, combined with metformin was assessed on bladder cancer and underlying mechanisms were explored. This drug combination induced a strong anti-proliferative and anti-colony forming effect and apoptosis in bladder cancer cell lines. Gefitinib suppressed EGFR signaling and inhibited phosphorylation of ERK and Akt. Metformin amplified this inhibitory effect and enhanced gefitinib-induced activation of AMPK signaling pathway. In vivo intravesical treatment of metformin and gefitinib on syngeneic orthotopic mice confirmed the significant inhibitory effect on bladder tumor growth. These two drugs may be an excellent combination for the treatment of bladder cancer through intravesical instillation. PMID:27334428

  19. Tea Consumption and Risk of Bladder Cancer: A Dose-Response Meta-Analysis

    PubMed Central

    Weng, Hong; Zeng, Xian-Tao; Li, Sheng; Kwong, Joey S. W.; Liu, Tong-Zu; Wang, Xing-Huan

    2017-01-01

    Background and Objective: Controversial results of the association between tea (black tea, green tea, mate, and oolong tea) consumption and risk of bladder cancer were reported among epidemiological studies. Thus, we performed a meta-analysis of observational studies to investigate the association. Methods: We searched the PubMed and Embase for studies of tea consumption and bladder cancer that were published in any language up to March, 2016. Cohort or case-control studies were included in the meta-analysis. All statistical analyses were performed in Stata 12.0 software. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the relationship between tea consumption and risk of bladder cancer. Results: Totally, 25 case-control studies (15 643 cases and 30 795 controls) and seven prospective cohort studies (1807 cases and 443 076 participants) were included. The meta-analysis showed that tea consumption was not significantly associated with bladder cancer risk (OR = 0.96, 95% CI 0.86–1.06) (in a comparison of highest vs. lowest category). No non-linearity association was observed between tea consumption and bladder cancer risk (P = 0.51 for non-linearity). Specific analysis for black tea, green tea, and mate yielded similar results. The dose-response analysis showed the summary OR for an increment of 1 cup/day of tea consumption was 1.01 (95% CI 0.97–1.05). Conclusion: Results based on current meta-analysis indicated that no significant association was observed between tea consumption and risk of bladder cancer. PMID:28167914

  20. Association of smoking status with prognosis in bladder cancer: A meta-analysis

    PubMed Central

    Dai, Meng; Chen, Pengliang; Zhao, Hongfan; Wei, Qiang; Li, Fei; Tan, Wanlong

    2017-01-01

    There is considerable controversy regarding the association between smoking and prognosis in surgically treated bladder cancer. The present meta-analysis was performed to quantify the role of smoking status in bladder cancer recurrence, progression and patient survival by pooling the available previous data. Pubmed, Embase and the Cochrane Library databases were searched for eligible studies published prior to April 2016. Random and fixed effects models were used to calculate the summary relative risk estimates (SRRE). A total of 10,192 patients from 15 studies were included in the meta-analysis. There was evidence of positive associations between current smoking and the risk of recurrence (SRRE=1.23; 95% CI, 1.05–1.45) and mortality (SRRE=1.28; 95% CI, 1.07-1.52) in bladder cancer. Furthermore, former smoking had positive associations with bladder cancer recurrence (SRRE=1.22; 95% CI, 1.09-1.37) and mortality (SRRE=1.20; 95% CI, 1.03-1.41). However, there was no significant association between bladder cancer progression risk and current (SRRE=1.11; 95% CI, 0.71-1.75) or previous smoking (SRRE=1.16; 95% CI, 0.92-1.46). The findings indicate that current and former smoking increase the risk of recurrence and mortality in patients with bladder cancer. However, due to the nonrandomized and retrospective nature of the current study, patients may be prone to potential selection bias. Prospective and larger epidemiological studies with a longer follow-up are required to confirm these findings. PMID:27902481

  1. Diabetes Mellitus and Risk of Bladder Cancer: A Meta-Analysis of Cohort Studies

    PubMed Central

    Shen, Zhoujun; Zhong, Shan; Wang, Xianjin; Lu, Yingli; Xu, Chen

    2013-01-01

    Background Increasing evidence suggests that diabetes mellitus (DM) may be associated with an increased risk of bladder cancer. To provide a quantitative assessment of this association, we evaluated the relation between DM and incidence and mortality of bladder cancer in an updated meta-analysis of cohort studies. Methods We identified cohort studies by searching the EMBASE and MEDLINE databases, through 31 March 2012. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with random-effects models. Results A total of 29 cohort studies (27 articles) were included in this meta-analysis. DM was associated with an increased incidence of bladder cancer (RR 1.29, 95% CI: 1.08–1.54), with significant evidence of heterogeneity among these studies (p<0.001, I2 = 94.9%). In stratified analysis, the RRs of bladder cancer were 1.36 (1.05–1.77) for diabetic men and 1.28 (0.75–2.19) for diabetic women, respectively. DM was also positively associated with bladder cancer mortality (RR 1.33, 95% CI: 1.14–1.55), with evident heterogeneity between studies (p = 0.002, I2 = 63.3%). The positive association was observed for both men (RR 1.54, 95% CI: 1.30–1.82) and women (RR 1.50, 95% CI: 1.05–2.14). Conclusion These findings suggest that compared to non-diabetic individuals, diabetic individuals have an increased incidence and mortality of bladder cancer. PMID:23437204

  2. Dipstick Urinalysis as a Test for Microhematuria and Occult Bladder Cancer

    PubMed Central

    Matulewicz, Richard S.; DeLancey, John Oliver; Pavey, Emily; Schaeffer, Edward M.; Popescu, Oana; Meeks, Joshua J.

    2017-01-01

    Introduction: There is a lack of evidence supporting the routine use of laboratory tests to detect bladder cancer. Identifying a cost-effective and widely available diagnostic aid may improve bladder cancer outcomes. We sought to evaluate the utility of dipstick urinalysis to detect microhematuria and diagnose bladder cancer in a large, diverse, contemporary cohort. Methods: All non-pregnant women and men 35 and older with a new diagnosis of microhematuria (≥3 RBC/hpf) were identified via a multi-center electronic medical record data warehouse query. Negative controls with no history of hematuria were randomly chosen and included to complete our cohort. Comparison between dipstick urinalysis and microscopic urinalysis on self-matched patients for the detection of microhematuria and diagnosis of bladder cancer was performed via Spearman’s rank correlation coefficient, sensitivity/specificity testing, and ROC curve analysis. Results: A total of 46,842 patients were included. Spearman’s rank order correlation (rho = 0.66) between degree of microhematuria on dipstick urinalysis and microscopic urinalysis indicated a strong positive relationship. The ROC curve for dipstick urinalysis to identify microhematuria had an AUC of 0.80 (95% CI 0.79–0.81). No difference (p = 0.83) in diagnostic accuracy between dipstick urinalysis (AUC 0.74, 95% CI 0.70–0.78) and microscopic urinalysis (AUC 0.73, 95% CI 0.69–0.78) as a test for bladder cancer was found. Conclusion: Dipstick urinalysis provides a highly specific test for microhematuria and similar accuracy to microscopic urinalysis when used as a diagnostic tool to detect bladder cancer. PMID:28149934

  3. Tea Consumption and Risk of Bladder Cancer: A Dose-Response Meta-Analysis.

    PubMed

    Weng, Hong; Zeng, Xian-Tao; Li, Sheng; Kwong, Joey S W; Liu, Tong-Zu; Wang, Xing-Huan

    2016-01-01

    Background and Objective: Controversial results of the association between tea (black tea, green tea, mate, and oolong tea) consumption and risk of bladder cancer were reported among epidemiological studies. Thus, we performed a meta-analysis of observational studies to investigate the association. Methods: We searched the PubMed and Embase for studies of tea consumption and bladder cancer that were published in any language up to March, 2016. Cohort or case-control studies were included in the meta-analysis. All statistical analyses were performed in Stata 12.0 software. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the relationship between tea consumption and risk of bladder cancer. Results: Totally, 25 case-control studies (15 643 cases and 30 795 controls) and seven prospective cohort studies (1807 cases and 443 076 participants) were included. The meta-analysis showed that tea consumption was not significantly associated with bladder cancer risk (OR = 0.96, 95% CI 0.86-1.06) (in a comparison of highest vs. lowest category). No non-linearity association was observed between tea consumption and bladder cancer risk (P = 0.51 for non-linearity). Specific analysis for black tea, green tea, and mate yielded similar results. The dose-response analysis showed the summary OR for an increment of 1 cup/day of tea consumption was 1.01 (95% CI 0.97-1.05). Conclusion: Results based on current meta-analysis indicated that no significant association was observed between tea consumption and risk of bladder cancer.

  4. Pioglitazone (Actos) and bladder cancer: Legal system triumphs over the evidence.

    PubMed

    Davidson, Mayer B

    2016-08-01

    In preclinical studies, pioglitazone was associated with bladder cancer in male rats (but not in female rats, mice dogs or monkeys). Because of this association, the Federal Drug Administration requested a large 10year epidemiological study to evaluate whether there was an association between bladder cancer and exposure to pioglitazone in patients. A 5-year interim report published in 2011 showed no significant association between ever vs never exposure to the drug but a significant association in patients exposed to pioglitazone for >2years. Importantly, the final 10year report did not confirm the 5year interim report finding no association between bladder cancer and pioglitazone, even after >4years of exposure to the drug. However, as would be expected, following the 5-year interim report, many epidemiological studies were carried out and civil litigation lawsuits began to be filed. Of the 23 epidemiological studies that have been published to date, 18 showed no association between bladder cancer and pioglitazone (5 with a combination of rosiglitazone and pioglitazone). Of the five that did show a significant association with pioglitazone, three could not be confirmed in the same population and in one of them there were significantly more risk factors for bladder cancer in the patients exposed to pioglitazone. In the fourth one, a significant association became non-significant when patients >79years were included. In the fifth one, detection bias was a major flaw. Currently, >11,000 legal cases have been filed, many of which claim emotional distress due to the fear of bladder cancer. To limit their legal costs, the pharmaceutical company has established a 2.4 billion dollar settlement pool. So much for evidence-based medicine.

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

    PubMed

    Li, Fei; An, Shengli; Hou, Lina; Chen, Pengliang; Lei, Chengyong; Tan, Wanlong

    2014-01-01

    Findings from epidemiologic studies concerning red and processed meat intake and bladder cancer risk remain conflicting. Thus, we conducted this meta-analysis to examine the associations of red and processed meat intake with bladder cancer. Eligible studies published up to May 2014 were retrieved via both computer searches and review of references. Finally, we identified 14 studies on red meat (involving 9,084 cases) and 11 studies on processed meat (7,562 cases) involving up to 1,558,848 individuals. Random-effects models were used to estimate summary relative risk estimates (SRRE) based on high vs. low intake, and heterogeneity between study results was explored through stratified analyses on the basis of red/processed meat category, gender, study design and geographical region. Overall, the SRRE for all studies regarding red meat intake was 1.15 (95% CI: 0.97-1.36). Significant positive association was observed between processed meat consumption and bladder cancer (SRRE = 1.22; 95% CI: 1.04-1.43). Interestingly, increased by 25% and 33% risk of bladder cancer were observed for red meat and processed meat intake respectively in populations from the American continent. In conclusion, our fi ndings showed that there was an absence of an association between red meat intake and bladder cancer, but suggested that high consumption of processed meat probably correlated with rising risk of bladder cancer. In addition, positive relationships were observed regarding people intake of red and processed meat in the American continent. These findings need to be confirmed in future research.

  6. Metformin represses bladder cancer progression by inhibiting stem cell repopulation via COX2/PGE2/STAT3 axis

    PubMed Central

    Tong, Dali; Liu, Gaolei; Lan, Weihua; Zhang, Dianzheng; Xiao, Hualiang; Zhang, Yao; Huang, Zaoming; Yang, Junjie; Zhang, Jun; Jiang, Jun

    2016-01-01

    Cancer stem cells (CSCs) are a sub-population of tumor cells playing essential roles in initiation, differentiation, recurrence, metastasis and development of drug resistance of various cancers, including bladder cancer. Although multiple lines of evidence suggest that metformin is capable of repressing CSC repopulation in different cancers, the effect of metformin on bladder cancer CSCs remains largely unknown. Using the N-methyl-N-nitrosourea (MNU)-induced rat orthotropic bladder cancer model, we demonstrated that metformin is capable of repressing bladder cancer progression from both mild to moderate/severe dysplasia lesions and from carcinoma in situ (CIS) to invasive lesions. Metformin also can arrest bladder cancer cells in G1/S phases, which subsequently leads to apoptosis. And also metformin represses bladder cancer CSC repopulation evidenced by reducing cytokeratin 14 (CK14+) and octamer-binding transcription factor 3/4 (OCT3/4+) cells in both animal and cellular models. More importantly, we found that metformin exerts these anticancer effects by inhibiting COX2, subsequently PGE2 as well as the activation of STAT3. In conclusion, we are the first to systemically demonstrate in both animal and cell models that metformin inhibits bladder cancer progression by inhibiting stem cell repopulation through the COX2/PGE2/STAT3 axis. PMID:27058422

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

    PubMed

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

    2016-05-03

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

  8. The impact of advanced proteomics in the search for markers and therapeutic targets of bladder cancer.

    PubMed

    Zhang, Hongshuo; Fan, Yue; Xia, Lingling; Gao, Chunhui; Tong, Xin; Wang, Hanfu; Sun, Lili; Ji, Tuo; Jin, Mingyu; Gu, Bing; Fan, Bo

    2017-03-01

    Bladder cancer is the most common cancer of the urinary tract and can be avoided through proper surveillance and monitoring. Several genetic factors are known to contribute to the progression of bladder cancer, many of which produce molecules that serve as cancer biomarkers. Blood, urine, and tissue are commonly analyzed for the presence of biomarkers, which can be derived from either the nucleus or the mitochondria. Recent advances in proteomics have facilitated the high-throughput profiling of data generated from bladder cancer-related proteins or peptides in parallel with high sensitivity and specificity, providing a wealth of information for biomarker discovery and validation. However, the transmission of screening results from one laboratory to another remains the main disadvantage of these methods, a fact that emphasizes the need for consistent and standardized procedures as suggested by the Human Proteome Organization. This review summarizes the latest discoveries and progress of biomarker identification for the early diagnosis, projected prognosis, and therapeutic response of bladder cancer, informs the readers of the current status of proteomic-based biomarker findings, and suggests avenues for future work.

  9. [Immunocorrective effect of alternating magnetic field in the postoperative period in malignant bladder cancer].

    PubMed

    Zlatnik, E Iu; Kapkina, N N; Zaderin, V P; Zakora, G I

    2001-01-01

    The study deals with immune status of patients operated for bladder cancer and exposed postoperatively to alternating magnetic field (MF) (hypothalamus and operative field). MF application was followed by higher T- and B-lymphocyte and CD4+, CD16+ cell levels as well as enhanced T-cell activity; no postoperative complications were registered and tumor relapse rates were relatively low. The effect was likely to be due to antistressor influence of MF. The procedure may substitute drug therapy for immunocorrection and to avoid recurrence of bladder cancer.

  10. Concurrent bladder cancer in patients undergoing photodynamic diagnostic ureterorenoscopy: how many lesions do we miss under white light cystoscopy?

    PubMed Central

    Zreik, Abdullah; Ahmad, Sarfraz; Chłosta, Piotr; Aboumarzouk, Omar

    2016-01-01

    Introduction There is an ongoing debate on panurothelial changes in the upper and lower urinary tract as multifocal presentation of urothelial cancer is well recognised. Concurrent bladder cancer impacts the outcome of the upper urinary tract urothelial cancer treatment, while its detection still relies on the white light cystoscopy. Material and methods We retrospectively reviewed all patients who underwent photodynamic diagnostic ureterorenoscopy, choosing those who had synchronous bladder biopsies. Each patient received 20 mg/kg body weight of oral 5-Aminolevulinic acid around 3–4 hours before endoscopy. All procedures were performed by a single endourologist experienced in photodynamic diagnosis and flexible ureterorenoscopy. Results Between July 2009 and June 2013, 69 patients underwent bladder biopsies at the time of photodynamic diagnostic endoscopic inspection of the upper urinary tract. In total, 43.5% (30/69) patients were found to have bladder lesions, of which 43.3% (13/30) were proven to be carcinoma in situ. White light inspection of the bladder missed bladder cancer in 16 (23.1%) patients, of which 12 were carcinoma in situ. There were 14 bladder cancer lesions missed under white light which were concomitant to the upper urinary tract urothelial cancer. Twelve (17.4%) patients developed minor complications relevant to the photosensitizer. Conclusions The study raises a concern about missing small bladder cancer/carcinoma in situ lesions on the initial diagnosis or in surveillance of the upper urinary tract urothelial cancer. Higher than previously reported, the rate of concomitant bladder cancer may suggest utilisation of photodynamic diagnosis to ensure the cancer free status of the bladder, but this needs to be ratified in a multi-institutional randomised trial. PMID:28127447

  11. Disulfide-crosslinked nanomicelles confer cancer-specific drug delivery and improve efficacy of paclitaxel in bladder cancer

    NASA Astrophysics Data System (ADS)

    Pan, Amy; Zhang, Hongyong; Li, Yuanpei; Lin, Tzu-yin; Wang, Fuli; Lee, Joyce; Cheng, Mingshan; Dall'Era, Marc; Li, Tianhong; deVere White, Ralph; Pan, Chong-Xian; Lam, Kit S.

    2016-10-01

    Chemotherapy commonly used in the treatment of advanced bladder cancer is only moderately effective and associated with significant toxicity. There has been no appreciable improvement in overall survival over the last three decades. The goal of this project is to develop and characterize bladder cancer-specific nanometer-scale micelles loaded with the chemotherapeutic drug paclitaxel (PTX) and determine the anti-tumor activity and toxicity. Micelle-building-material telodendrimers were synthesized through the stepwise conjugation of eight cholic acid units at one terminus of polyethylene glycol (PEG) and a bladder cancer-specific targeting peptide named PLZ4 at the other terminus. To synthesize disulfide-crosslinked PLZ4 nanomicelles (DC-PNM), cysteine was introduced between the cholic acid and PEG. DC-PNM-PTX was synthesized through the evaporation method by loading PTX in the core. The loading capacity of PTX in DC-PNM was 25% (W/W). The loading efficiency was over 99%. DC-PNM-PTX was spherical with the median size of 25 nm. The stability of DC-PNM-PTX was determined in a solution containing sodium docecyl sulfate (SDS). It was stable in a SDS solution, but dissolved within 5 min after the addition of glutathione at the physiological intracellular concentration of 10 mM. In vivo targeting and anti-tumor activity were determined in immunodeficient mice carrying patient-derived bladder cancer xenografts (PDXs). After intravenous administration, DC-PNM specifically targeted the bladder cancer PDXs, but very little to the lung cancer xenografts in the same mice (p < 0.001). DC-PNM loaded with PTX overcame cisplatin resistance, and improved the median survival from 55 d with free PTX to 69.5 d (p = 0.03) of mice carrying PDXs. In conclusion, DC-PNM remained stable in the SDS solution, specifically targeted the bladder cancer xenografts in vivo, and improved the anti-cancer efficacy of PTX.

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

    PubMed

    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

  13. Surveillance of nasal and bladder cancer to locate sources of exposure to occupational carcinogens.

    PubMed Central

    Teschke, K; Morgan, M S; Checkoway, H; Franklin, G; Spinelli, J J; van Belle, G; Weiss, N S

    1997-01-01

    OBJECTIVE: To locate sources of occupational exposure to nasal and bladder carcinogens for surveillance follow up in British Columbia, Canada. METHODS: Incident cases of nasal cancer (n = 48), bladder cancer (n = 105), and population based controls (n = 159) matched for sex and age, were interviewed about their jobs, exposures, and smoking histories. Odds ratios (ORs) were calculated for 57 occupational groups with stratified exact methods to control for age, sex, and smoking. RESULTS: Occupational groups at increased risk of nasal cancer included: textile workers (six cases, OR 7.6); miners, drillers, and blasters (six cases, OR 3.5); welders (two cases, OR 3.5); pulp and paper workers (three cases, OR 3.1); and plumbers and pipefitters (two cases, OR 3.0). Nasal cancer ORs were not increased in occupations exposed to wood dust, possibly due to low exposures in local wood industries. Strongly increased risks of bladder cancer were found for sheet metal workers (four cases, OR 5.3), miners (19 cases, OR 4.5), gardeners (six cases, OR 3.7), and hairdressers (three cases, OR 3.2). Among occupations originally considered at risk, the following had increased risks of bladder cancer: painters (four cases, OR 2.8); laundry workers (five cases, OR 2.3); chemical and petroleum workers (15 cases, OR 1.8); machinists (eight cases, OR 1.6); and textile workers (three cases, OR 1.5). CONCLUSIONS: Occupational groups with increased risks and three or more cases with similar duties were selected for surveillance follow up. For nasal cancer, these included textile workers (five were garment makers) and pulp and paper workers (three performed maintenance tasks likely to entail stainless steel welding). For bladder cancer, these included miners (12 worked underground), machinists (five worked in traditional machining), hairdressers (three had applied hair dyes), and laundry workers (three were drycleaners). PMID:9245952

  14. Prediction of Bacillus Calmette-Guerin Response in Patients with Bladder Cancer after Transurethral Resection of Bladder Tumor by Using Genetic Variation Based on Genomic Studies

    PubMed Central

    Zhang, Ning; Jiang, Guangliang; Liu, Xu; Xu, Jianfeng

    2016-01-01

    Purpose. We aimed to comprehensively review contemporary literature on genetic and epigenetic biomarkers associated with the prediction of Bacillus Calmette-Guerin (BCG) response after the transurethral resection of a bladder tumor and to discuss the application of these biomarkers in precision cancer care for bladder cancer. Method. We performed a systematic review of published literatures in the databases PubMed and Embase by using the following key words: bladder cancer, BCG, gene, and methylation. Studies associated with cell lines, animal models, and muscle invasive bladder cancer were excluded. Results. The genetic variations associated with BCG response can be classified into three categories: germline variations, somatic variations, and epigenetic alterations. Genes related to BCG response were mainly involved in single-nucleotide polymorphisms, copy number variations, and gene methylations. Conclusions. Although these gene alterations are currently the most promising predictive markers of BCG response, most studies about bladder cancer DNA biomarkers are related to germline variations in candidate genes, and the results are not consistent. Only one study is related to somatic variation, and further evaluation in large-scale validation studies should be conducted to assess the potential clinical application of these findings. In addition, other biomarkers based on different “–omics” technologies should be considered in future studies. PMID:27896277

  15. Sox4 Expression Confers Bladder Cancer Stem Cell Properties and Predicts for Poor Patient Outcome

    PubMed Central

    Shen, He; Blijlevens, Maxime; Yang, Nuo; Frangou, Costakis; Wilson, Kayla E.; Xu, Bo; Zhang, Yinglong; Zhang, Lirui; Morrison, Carl D.; Shepherd, Lori; Hu, Qiang; Zhu, Qianqian; Wang, Jianmin; Liu, Song; Zhang, Jianmin

    2015-01-01

    Genetic and epigenetic alterations have been identified as to contribute directly or indirectly to the generation of transitional cell carcinoma of the urinary bladder (TCC-UB). We have previously found that amplification of chromosome 6p22 is significantly associated with the muscle-invasive rather than superficial TCC-UB. Here, we demonstrated that Sox4, one of the candidate oncogenes located within the chromosome 6p22 amplicon, confers bladder cancer stem cell (CSC) properties. Down-regulation of Sox4 led to the inhibition of cell migration, colony formation as well as mesenchymal-to-epithelial transition (MET). Interestingly, knockdown of Sox4 also reduced the sphere formation, enriched cell population with high levels of aldehyde dehydrogenase (ALDH high) and tumor formation potential. Using gene expression profiling, we further identified novel Sox4 target genes. Last, immunohistochemistry analysis of human bladder tumor tissue microarrays (TMAs) indicated that high Sox4 expression was correlated with advanced cancer stages and poor survival rate. In summary, our data show that Sox4 is an important regulator of the bladder CSC properties and it may serve as a biomarker of the aggressive phenotype in bladder cancer. PMID:26681916

  16. Transforming growth factor alpha and epidermal growth factor levels in bladder cancer and their relationship to epidermal growth factor receptor.

    PubMed Central

    Mellon, J. K.; Cook, S.; Chambers, P.; Neal, D. E.

    1996-01-01

    We have examined levels of epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) in neoplastic and non-neoplastic bladder tissue using a standard radioimmunoassay technique. Tumour samples had much higher TGF-alpha levels compared with EGF and TGF-alpha levels in malignant tissue were significantly higher than in benign bladder samples. There was, in addition, a difference in mean EGF levels from 'normal' bladder samples from non-tumour bearing areas of bladder in patients with bladder cancer compared with 'normal' bladder tissue obtained at the time of organ retrieval surgery. Levels of EGF and TGF-alpha did not correlate with levels of EGF receptor (EGFR) as determined by a radioligand binding method but levels of TGF-alpha > 10 ng gm-1 of tumour tissue did correlate with EGFR positivity defined using immunohistochemistry. These data suggest that TGF-alpha is the likely ligand for EGFR in bladder tumours. PMID:8605103

  17. Dose Effect Relationship for Late Side Effects of the Rectum and Urinary Bladder in Magnetic Resonance Image-Guided Adaptive Cervix Cancer Brachytherapy

    SciTech Connect

    Georg, Petra; Poetter, Richard; Georg, Dietmar; Lang, Stefan; Dimopoulos, Johannes C.A.; Sturdza, Alina E.; Berger, Daniel; Kirisits, Christian; Doerr, Wolfgang

    2012-02-01

    Purpose: To establish dose-response relationships for late side effects of the rectum and bladder in cervix cancer patients after magnetic resonance image-guided adaptive brachytherapy (IGABT). Methods and Materials: A cohort of 141 patients was treated with 45 to 50.4 Gy with or without cisplatin plus 4 fractions of 7 Gy IGABT. Doses for the most exposed 2, 1, and 0.1-cm{sup 3} (D{sub 2cc}, D{sub 1cc}, D{sub 0.1cc}) volumes of the rectum and bladder were converted into the equivalent dose in 2 Gy fractions (EQD2), using a linear quadratic model ({alpha}/{beta} = 3 Gy). Late side effects were prospectively assessed (using late effects in normal tissues subjective, objective, management and analytic [LENT SOMA]) scales. Dose-response relationships were determined by logit analyses. Results: Eleven patients developed rectal side effects, and 23 patients had urinary side effects. A significant dose effect was found for all rectal dose-volume histogram (DVH) parameters for patients with side effect grades of 1 to 4 but was only significant for D{sub 2cc} and D{sub 1cc} for grades {>=}2. The ED10 values for D{sub 2cc} were 73 Gy for grades 1 to 4 and 78 Gy for grades 2 to 4 rectal morbidity. For bladder side effects, a significant dose effect was shown for all DVH parameters for complication grades {>=}2; the respective ED10 was 101 Gy. Conclusions: Well-defined dose-response curves could be established for D{sub 2cc} in the rectum and the urinary bladder.

  18. Three differentiation states risk-stratify bladder cancer into distinct subtypes.

    PubMed

    Volkmer, Jens-Peter; Sahoo, Debashis; Chin, Robert K; Ho, Philip Levy; Tang, Chad; Kurtova, Antonina V; Willingham, Stephen B; Pazhanisamy, Senthil K; Contreras-Trujillo, Humberto; Storm, Theresa A; Lotan, Yair; Beck, Andrew H; Chung, Benjamin I; Alizadeh, Ash A; Godoy, Guilherme; Lerner, Seth P; van de Rijn, Matt; Shortliffe, Linda D; Weissman, Irving L; Chan, Keith S

    2012-02-07

    Current clinical judgment in bladder cancer (BC) relies primarily on pathological stage and grade. We investigated whether a molecular classification of tumor cell differentiation, based on a developmental biology approach, can provide additional prognostic information. Exploiting large preexisting gene-expression databases, we developed a biologically supervised computational model to predict markers that correspond with BC differentiation. To provide mechanistic insight, we assessed relative tumorigenicity and differentiation potential via xenotransplantation. We then correlated the prognostic utility of the identified markers to outcomes within gene expression and formalin-fixed paraffin-embedded (FFPE) tissue datasets. Our data indicate that BC can be subclassified into three subtypes, on the basis of their differentiation states: basal, intermediate, and differentiated, where only the most primitive tumor cell subpopulation within each subtype is capable of generating xenograft tumors and recapitulating downstream populations. We found that keratin 14 (KRT14) marks the most primitive differentiation state that precedes KRT5 and KRT20 expression. Furthermore, KRT14 expression is consistently associated with worse prognosis in both univariate and multivariate analyses. We identify here three distinct BC subtypes on the basis of their differentiation states, each harboring a unique tumor-initiating population.

  19. Three differentiation states risk-stratify bladder cancer into distinct subtypes

    PubMed Central

    Volkmer, Jens-Peter; Sahoo, Debashis; Chin, Robert K.; Ho, Philip Levy; Tang, Chad; Kurtova, Antonina V.; Willingham, Stephen B.; Pazhanisamy, Senthil K.; Contreras-Trujillo, Humberto; Storm, Theresa A.; Lotan, Yair; Beck, Andrew H.; Chung, Benjamin I.; Alizadeh, Ash A.; Godoy, Guilherme; Lerner, Seth P.; van de Rijn, Matt; Shortliffe, Linda D.; Weissman, Irving L.; Chan, Keith S.

    2012-01-01

    Current clinical judgment in bladder cancer (BC) relies primarily on pathological stage and grade. We investigated whether a molecular classification of tumor cell differentiation, based on a developmental biology approach, can provide additional prognostic information. Exploiting large preexisting gene-expression databases, we developed a biologically supervised computational model to predict markers that correspond with BC differentiation. To provide mechanistic insight, we assessed relative tumorigenicity and differentiation potential via xenotransplantation. We then correlated the prognostic utility of the identified markers to outcomes within gene expression and formalin-fixed paraffin-embedded (FFPE) tissue datasets. Our data indicate that BC can be subclassified into three subtypes, on the basis of their differentiation states: basal, intermediate, and differentiated, where only the most primitive tumor cell subpopulation within each subtype is capable of generating xenograft tumors and recapitulating downstream populations. We found that keratin 14 (KRT14) marks the most primitive differentiation state that precedes KRT5 and KRT20 expression. Furthermore, KRT14 expression is consistently associated with worse prognosis in both univariate and multivariate analyses. We identify here three distinct BC subtypes on the basis of their differentiation states, each harboring a unique tumor-initiating population. PMID:22308455

  20. Large-Scale SRM Screen of Urothelial Bladder Cancer Candidate Biomarkers in Urine.

    PubMed

    Duriez, Elodie; Masselon, Christophe D; Mesmin, Cédric; Court, Magali; Demeure, Kevin; Allory, Yves; Malats, Núria; Matondo, Mariette; Radvanyi, François; Garin, Jérôme; Domon, Bruno

    2017-04-07

    Urothelial bladder cancer is a condition associated with high recurrence and substantial morbidity and mortality. Noninvasive urinary tests that would detect bladder cancer and tumor recurrence are required to significantly improve patient care. Over the past decade, numerous bladder cancer candidate biomarkers have been identified in the context of extensive proteomics or transcriptomics studies. To translate these findings in clinically useful biomarkers, the systematic evaluation of these candidates remains the bottleneck. Such evaluation involves large-scale quantitative LC-SRM (liquid chromatography-selected reaction monitoring) measurements, targeting hundreds of signature peptides by monitoring thousands of transitions in a single analysis. The design of highly multiplexed SRM analyses is driven by several factors: throughput, robustness, selectivity and sensitivity. Because of the complexity of the samples to be analyzed, some measurements (transitions) can be interfered by coeluting isobaric species resulting in biased or inconsistent estimated peptide/protein levels. Thus the assessment of the quality of SRM data is critical to allow flagging these inconsistent data. We describe an efficient and robust method to process large SRM data sets, including the processing of the raw data, the detection of low-quality measurements, the normalization of the signals for each protein, and the estimation of protein levels. Using this methodology, a variety of proteins previously associated with bladder cancer have been assessed through the analysis of urine samples from a large cohort of cancer patients and corresponding controls in an effort to establish a priority list of most promising candidates to guide subsequent clinical validation studies.

  1. Risk factors for bladder cancer: challenges of conducting a literature search using PubMed.

    PubMed

    Joshi, Ashish; Preslan, Elicia

    2011-04-01

    The objective of this study was to assess the risk factors for bladder cancer using PubMed articles from January 2000 to December 2009. The study also aimed to describe the challenges encountered in the methodology of a literature search for bladder cancer risk factors using PubMed. Twenty-six categories of risk factors for bladder cancer were identified using the National Cancer Institute Web site and the Medical Subject Headings (MeSH) Web site. A total of 1,338 PubMed searches were run using the term "urinary bladder cancer" and a risk factor term (e.g., "cigarette smoking") and were screened to identify 260 articles for final analysis. The search strategy had an overall precision of 3.42 percent, relative recall of 12.64 percent, and an F-measure of 5.39 percent. Although search terms derived from MeSH had the highest overall precision and recall, the differences did not reach significance, which indicates that for generalized, free-text searches of the PubMed database, the searchers' own terms are generally as effective as MeSH terms.

  2. ATM participates in the regulation of viability and cell cycle via ellipticine in bladder cancer

    PubMed Central

    Tao, Shuixiang; Meng, Shuai; Zheng, Xiangyi; Xie, Liping

    2017-01-01

    Ellipticine, an alkaloid isolated from Apocyanaceae plants, has been demonstrated to exhibit antitumor activity in several cancers. However, the effect and the mechanisms underlying its action have not been investigated in human bladder cancer cells. The aim of the present study was to investigate the effect and mechanism of ellipticine on the behavior of T-24 bladder cancer cells. T-24 cells were treated with varying concentrations and durations of ellipticine. Cell viability was evaluated by Cell Counting Kit-8 assay. Cell motility was analyzed by Transwell migration assay. Flow cytometry, reverse transcription-quantitative polymerase chain reaction and western blot analyses were performed to detect the cell cycle and signaling pathways involved. The results demonstrated that ellipticine suppressed proliferation and inhibited the migration ability of T-24 bladder cancer cells in a dose- and time-dependent manner, and resulted in G2/M cell cycle arrest. The mechanism of this action was demonstrated to be due to ellipticine-triggered activation of the ATM serine/threonine kinase pathway. These data therefore suggest that ellipticine may be effective towards treating human bladder cancer. PMID:28138703

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

    SciTech Connect

    Cengiz, Mustafa Guerdalli, Salih; Selek, Ugur; Yildiz, Ferah; Saglam, Yuecel; Ozyar, Enis; Atahan, I. Lale

    2008-02-01

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

  4. Sensitivity of bladder cancer cells to curcumin and its derivatives depends on the extracellular matrix.

    PubMed

    Hauser, Paul J; Han, Zhiyong; Sindhwani, Puneet; Hurst, Robert E

    2007-01-01

    Because the response of cancer cells to chemotherapeutic agents depends upon the supporting extracellular matrix (ECM), the response in vivo may not be reproduced in 2-dimensional cell culture. The dose-response to curcumin and two derivatives by bladder cancer cells grown on both normal (SISgel) and cancer-derived ECM (Matrigel) and on plastic were contrasted. Cells grown on Matrigel were resistant to curcumins, but cells growing on SISgel, which mimic cancer cells suppressed by normal ECM, were nearly as sensitive as cells grown on plastic. SV40-immortalized urothelial cells, which are models for premalignant cells, were the most sensitive, but even aggressive cell lines were nearly as sensitive when grown on SISgel as on plastic. Curcumin response depends highly on the supporting ECM, and cells grown on plastic poorly models cells growing on natural ECM. Curcumin could prove an effective chemopreventive for bladder cancer recurrence when administered intravesically post-therapy.

  5. Curcumin modulates micrRNA-203 mediated regulation of the Src-Akt axis in bladder cancer

    PubMed Central

    Saini, Sharanjot; Arora, Sumit; Majid, Shahana; Shahryari, Varahram; Chen, Yi; Deng, Guoren; Yamamura, Soichiro; Ueno, Koji; Dahiya, Rajvir

    2014-01-01

    Bladder cancer is often associated with recurrence and progression to invasive metastatic disease that have palliative therapeutic options. The use of traditional chemotherapeutic agents for bladder cancer management often suffer from toxicity and resistance concerns. This emphasizes the need for development of safer, natural, non-toxic compounds as chemotherapeutic/chemopreventive agents. Curcumin (diferuloylmethane) is a natural compound that has been known to possess anti-cancer properties in various cancers, including bladder cancer. However, the biological targets of curcumin are not well defined. Recently, it has been proposed that curcumin may mediate epigenetic modulation of expression of microRNAs (miRNAs). In this report, we define for the first time, that curcumin directly induces a tumor-suppressive miRNA, miR-203, in bladder cancer. miR-203 is frequently downregulated in bladder cancer due to DNA of its promoter. We studied the functional significance of miR-203 in bladder cancer cell lines and found that miR-203 has tumor suppressive properties. Also, we define Akt2 and Src as novel miR-203 targets in bladder cancer. Curcumin induces hypomethylation of the miR-203 promoter and subsequent upregulation of miR-203 expression. This leads to downregulation of miR-203 target genes Akt2 and Src that culminates in decreased proliferation and increased apoptosis of bladder cancer cells. This is the first report that shows a direct effect of curcumin on inducing epigenetic changes at a miRNA promoter with direct biological consequences. Our study suggests that curcumin may offer a therapeutic advantage in the clinical management of refractory bladder cancer over other standard treatment modalities. PMID:21836020

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

    PubMed Central

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

    2017-01-01

    Objective To evaluate the consistency of the results of patients who were treated for non-muscle-invasive bladder cancer (NMIBC) in our clinic with the European Organization for Research and Treatment of Cancer (EORTC) risk table. Material and methods Data were retrospectively analyzed from 452 patients who had undergone transurethral resection of bladder tumor (TUR-BT) between the years 2002, and 2010 for primary or recurrent NMIBC. Our study had a retrospective design but based on prospective cohort study. Patients were staged according to the 2002 Tumor Node Metastasis (TNM) classification and the 1973 World Health Organization grading system. Recurrence was defined as non-muscle-invasive or muscle-invasive and progression as muscle-invasive tumor determined based on following cystoscopy and TUR-BT results, and confirmed by histopathologic analysis. Patients in the current study were classified into four groups according to the EORTC risk tables. Time to first recurrence and progression was determined for each risk group. Results Of the 452 patients, 348 were enrolled in this study. The overall mean follow-up period was 55.25 months of all patients. Of 348 patients, 130 (37.4%) and 258 patients (74.1%) had recurrence after treatment at the 1 and 5 year follow-up period, respectively. While 35 (10.1%) and 99 patients (28.4%) progressed to muscle-invasive cancer at the 1 and 5 year follow-up period, respectively. In the multivariate analysis, grade, number, size of the tumor size, and concomitant carcinoma in situ were found to be statistically significant for disease progression and recurrence. Conclusion When EORTC risk tables were comparatively evaluated in our patient population, we can say that EORTC tables predict nearly accurately the clinical course of patients with NMIBC. PMID:28270951

  7. Case-control study of high risk occupations for bladder cancer in New Zealand.

    PubMed

    Dryson, Evan; 't Mannetje, Andrea; Walls, Chris; McLean, Dave; McKenzie, Fiona; Maule, Milena; Cheng, Soo; Cunningham, Chris; Kromhout, Hans; Boffetta, Paolo; Blair, Aaron; Pearce, Neil

    2008-03-15

    We conducted a nationwide case-control study of bladder cancer in adult New Zealanders to identify occupations that may contribute to the risk of bladder cancer in the New Zealand population. A total of 213 incident cases of bladder cancer (age 25-70 years) notified to the New Zealand Cancer Registry during 2003 and 2004, and 471 population controls, were interviewed face-to-face. The questionnaire collected demographic information and a full occupational history. The relative risks for bladder cancer associated with ever being employed in particular occupations and industries were calculated by unconditional logistic regression adjusting for age, sex, smoking and socio-economic status. Estimates were subsequently semi-Bayes adjusted to account for the large number of occupations and industries being considered. An elevated bladder cancer risk was observed for hairdressers (odds ratio (OR) 9.15 95% Confidence Interval (95%CI) 1.60-62.22), and sewing machinists (OR 3.07 95%CI 1.35-6.96). Significantly increased risks were not observed for several other occupations that have been reported in previous studies, including sales assistants (OR 1.03 95%CI 0.64-1.67), painters and paperhangers (OR 1.42 95%CI 0.56-3.60), sheet metal workers (OR 0.39, 95%CI 0.15-1.00), printing trades workers (OR 1.11 95%CI 0.41-3.05) and truck drivers (OR 1.36 95%CI 0.60-3.09), although the elevated odds ratios for painters, printers and truck drivers are consistent with excesses observed in other studies. Nonsignificantly increased risks were observed for tailors and dressmakers (OR 2.84 95%CI 0.62-13.05), rubber and plastics products machine operators (OR 2.82 95%CI 0.75-10.67), building workers (OR 2.15, 95%CI 0.68-6.73), and female market farmers and crop growers (OR 2.05 95%CI 0.72-5.83). In conclusion, this study has confirmed that hairdressers and sewing machinists are high risk occupations for bladder cancer in New Zealand, and has identified several other occupations and industries

  8. VIP neobladder (Padovana) reconstruction following radical cystectomy for bladder cancer Complications, functional outcome and quality of life evaluation in 95 cases.

    PubMed

    Kostakopoulos, Nikolaos; Protogerou, Vassilis; Skolarikos, Andreas; Varkarakis, Ioannis; Papatsoris, Athanasios; Troupis, Theodore; Piagou, Maria; Deliveliotis, Charalambos

    2015-01-01

    The Authors report a complete study concerning complications, the imaging and functional results, the clinical outcome and the quality of life in patients treated with VIP. 95 patients with localized bladder TCC (T2N0M0) were evaluated. Follow up points were 1st, 3rd, 6th, 12th, 18th, 24th and 36th month with clinical and ultrasound evaluation. At 6th, 12th and 36th month CT pyelography and urodynamic evaluation were performed and we used a questionnaire for subjective bladder function and the EORTC QLQ C-30 questionnaire to evaluate quality of life. Perioperative complications were ileus (2 patients; 2.1%) (Clavien Grade IIIb), one postoperative death (1.0%) (Clavien Grade V) and a resuscitated cardiac arrest (1.0%) (Clavien Grade IVa). Postoperative complications were incisional hernias (n=4 patients; 4.21%) (Clavien Grade I) and hydronephrosis in five patients (5.26%) due to ureteric/neobladder stricture (Clavien Grade IIIb). Urine retention due to neobladder neck stenosis was observed in one patient (1.0%) (Clavien Grade IIIb) and an ileo-neobladder fistula in one (1.0%) patient (Clavien Grade IIIb). During follow up there were two cancer related deaths (2.1%). According to urodynamic evaluations neobladder capacity increased, end-filling pressure and Qmax decreased while residual urine and the number of intrinsic contractions remained stable. Continence rates and quality of life were high and stable during follow up. VIP technique for bladder substitution is a relatively easy technique with low rate of complications, good functional results which respect the patient's quality of life.

  9. Curcumin modulates microRNA-203-mediated regulation of the Src-Akt axis in bladder cancer.

    PubMed

    Saini, Sharanjot; Arora, Sumit; Majid, Shahana; Shahryari, Varahram; Chen, Yi; Deng, Guoren; Yamamura, Soichiro; Ueno, Koji; Dahiya, Rajvir

    2011-10-01

    Bladder cancer is often associated with recurrence and progression to invasive metastatic disease that have palliative therapeutic options. The use of traditional chemotherapeutic agents for bladder cancer management often suffers from toxicity and resistance concerns. This emphasizes the need for development of safer, natural, nontoxic compounds as chemotherapeutic/chemopreventive agents. Curcumin (diferuloylmethane) is a natural compound that has been known to possess anticancer properties in various cancers, including bladder cancer. However, the biological targets of curcumin are not well defined. Recently, it has been proposed that curcumin may mediate epigenetic modulation of expression of microRNAs (miRNA). In this article, we define for the first time, that curcumin directly induces a tumor-suppressive miRNA, miR-203, in bladder cancer. miR-203 is frequently downregulated in bladder cancer due to DNA hypermethylation of its promoter. We studied the functional significance of miR-203 in bladder cancer cell lines and found that miR-203 has tumor suppressive properties. Also, we define Akt2 and Src as novel miR-203 targets in bladder cancer. Curcumin induces hypomethylation of the miR-203 promoter and subsequent upregulation of miR-203 expression. This leads to downregulation of miR-203 target genes Akt2 and Src that culminates in decreased proliferation and increased apoptosis of bladder cancer cells. This is the first report that shows a direct effect of curcumin on inducing epigenetic changes at a miRNA promoter with direct biological consequences. Our study suggests that curcumin may offer a therapeutic advantage in the clinical management of refractory bladder cancer over other standard treatment modalities.

  10. Can CT Virtual Cystoscopy Replace Conventional Cystoscopy in Early Detection of Bladder Cancer?

    PubMed Central

    Abrol, Sachin; Jairath, Ankush; Ganpule, Sanika; Ganpule, Arvind; Mishra, Shashikant; Sabnis, Ravindra; Desai, Mahesh

    2015-01-01

    Aim. To correlate findings of conventional cystoscopy with CT virtual cystoscopy (CTVC) in detecting bladder tumors and to evaluate accuracy of virtual cystoscopy in early detection of bladder cancer. Material and Method. From June 2013 to June 2014, 50 patients (46 males, four females) with history and investigations suggestive of urothelial cancer, with mean age 62.76 ± 10.45 years, underwent CTVC by a radiologist as per protocol and subsequently underwent conventional cystoscopy (CPE) the same day or the next day. One urologist and one radiologist, blinded to the findings of conventional cystoscopy, independently interpreted the images, and any discrepant readings were resolved with consensus. Result. CTVC detected 23 out of 25 patients with bladder tumor(s) correctly. Two patients were falsely detected as negative while two were falsely labeled as positive in CTVC. Virtual and conventional cystoscopy were comparable in detection of tumor growth in urinary bladder. The sensitivity, specificity, positive predictive value, and negative predictive value of virtual cystoscopy were 92% each. Conclusion. CTVC correlates closely with the findings of conventional cystoscopy. Bladder should be adequately distended and devoid of urine at the time of procedure. However, more studies are required to define the role of virtual cystoscopy in routine clinical practice. PMID:26600802

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-05-07

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

  13. Bladder cancer and occupation: a case-control study in northern Italy.

    PubMed Central

    Porru, S; Aulenti, V; Donato, F; Boffetta, P; Fazioli, R; Cosciani Cunico, S; Alessio, L

    1996-01-01

    OBJECTIVES--A hospital based case-control study was conducted between 1992 and 1993 in the province of Brescia, a highly industrialised area in northern Italy, to evaluate occupational risk factors of bladder cancer. METHODS--The study evaluated 355 histologically confirmed cases of bladder cancer (275 men, 80 women) and 579 controls affected by urological non-neoplastic diseases (397 men, 182 women). Lifetime occupational history, smoking and drinking habits, and sociodemographic characteristics were recorded by means of a structured questionnaire. Odds ratios (ORs) were computed with adjustment for age, smoking, alcohol and coffee consumption, education, and place of residence. RESULTS--A significant (P < 0.05) increase of risk of bladder cancer were found in men for labourers in the construction industry (OR 2.1, 95% confidence interval (95% CI) 1.1-3.9) and for recreational and cultural services (OR 5.0, 95% CI 1.3-18.9). Increased risks, although not significant, were found for various other occupations and industries such as machinery mechanics, metal processers and polishers, blacksmiths, gunsmiths, painters; for transport workers, an increased risk with increasing duration of employment was found. CONCLUSIONS--Occupational exposures seem to contribute to bladder cancer risk in the area under study. PMID:8563860

  14. HER-2/neu raises SHP-2, stops IFN-{gamma} anti-proliferation in bladder cancer

    SciTech Connect

    Su, W.-P.; Tu, I-H.; Hu, S.-W.; Yeh, H.-H.; Shieh, D.-B.; Chen, T.-Y.; Su, W.-C. . E-mail: sunnysu@mail.ncku.edu.tw

    2007-04-27

    Gene amplification or HER-2/neu protein overexpression signals a poor outcome for bladder cancer patients. We investigated the anti-proliferative effect of IFN-{gamma} in HER-2/neu-transfected human bladder cancer cells (TCC-N5 and TCC-N10). The cells continued growing after IFN-{gamma} stimulation but did not activate the Janus kinase (Jak)/Stat pathway. We found Jak/Stat protein phosphatase in TCC-N5 and TCC-N10 cells with upregulated Src homology 2-containing protein tyrosine phosphatase-2 (SHP-2). After the cells had been treated with AG825, a HER-2/neu-specific inhibitor, SHP-2 expression declined, and Jak2/Stat1 reactivated. Similar results were reported in a mouse bladder cancer cell line, MBT2, with constitutive HER-2/neu overexpression. Further, AG825 pretreatment restored the anti-proliferation activity of IFN-{gamma} in TCC-N5 and TCC-N10 cells. Therefore, the suppression of IFN-{gamma} signaling in HER-2/neu-overexpressing bladder cancer cells might be due to SHP-2 upregulation. The regulation of SHP-2 by HER-2/neu provides a new target for blocking the HER-2/neu oncogenic pathwa000.

  15. Pesticide exposure and risk of bladder cancer: A meta-analysis

    PubMed Central

    Xie, Bo; Zhu, Yi; Wu, Jian; Li, Shiqi; Meng, Shuai; Zheng, Xiangyi; Ji, Alin; Xie, Liping

    2016-01-01

    Objective We conducted a meta-analysis to quantitatively evaluate the correlation between pesticide exposure and the risk of bladder cancer by summarizing the results of published case-control and cohort studies. Methods A systematic literature search of articles update to February 2015 was conducted via Pubmed, Web of Science, Cochrane Library, and the Chinese National Knowledge Infrastructure (CNKI) databases, and the references of the retrieved articles. Fixed- or random-effect models were used to summarize the estimates of OR with 95% CIs for the highest versus the lowest exposure of pesticide. Results The pooled OR estimates indicated that pesticide exposure was associated with an increased risk of bladder cancer (OR=1.649, 95% CI 1.223-2.223). In subgroup analysis, we detected pesticide exposure demonstrated as a significant risk factor on bladder cancer in America (OR=1.741, 95% CI 1.270-2.388). Similar results were discovered in both case-control group and cohort group (OR=2.075, 95% CI 1.183-3.638, OR=1.146, 95% CI 1.074-1.223, respectively). No evidence of publication bias was found by Begg's or Egger's test (P = 0.210, P = 0.358, respectively). Conclusion In conclusion, our meta-analysis indicated that pesticide exposure was associated with an increased risk of bladder cancer. Further researches should be conducted to confirm the findings in our study and better clarify the potential biological mechanisms. PMID:27557494

  16. Personal hair dye use and bladder cancer: a meta-analysis.

    PubMed

    Turati, Federica; Pelucchi, Claudio; Galeone, Carlotta; Decarli, Adriano; La Vecchia, Carlo

    2014-02-01

    Despite considerable research, the issue of hair dyes and bladder cancer is still open to discussion. In January 2013, we searched in PubMed/EMBASE to identify observational studies investigating the association between personal use of hair dyes and bladder cancer incidence/mortality. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated using random-effects models. Fifteen case-control and two cohort studies were available for meta-analysis (8504 cases/deaths, 14,102 controls, and 617,937 persons at risk). Compared with no use, the pooled RR of bladder cancer for personal use of any type of hair dyes was 0.93 (95% CI, 0.82-1.05), with moderate heterogeneity among studies (I(2) = 34.1%, P = .07). Similar RRs were found for females (RR = 0.95) and males (RR = 0.81). Based on seven studies, the pooled RR for personal use of permanent hair dyes was 0.92 (95% CI, 0.77-1.09). Compared with no use, no association was observed for the highest categories of duration of use and lifetime frequency of use of both any type of dyes and permanent dyes. The pooled RR from four studies reporting results for use of dark-colored dyes was 1.29 (95% CI, 0.98-1.71). This meta-analysis allows to definitively exclude any appreciable excess risk of bladder cancer among personal hair dye users.

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

  18. Quantitative exposure to metalworking fluids and bladder cancer incidence in a cohort of autoworkers.

    PubMed

    Friesen, Melissa C; Costello, Sadie; Eisen, Ellen A

    2009-06-15

    Occupations with mineral oil exposure have been associated with bladder cancer in population-based case-control studies. The authors report results from the first cohort study to examine bladder cancer incidence in relation to quantitative exposures to metalworking fluids (MWFs), based on 21,999 male Michigan automotive workers, followed from 1985 through 2004. Cox regression was used to estimate hazard ratios based on categorical exposure variables for straight, soluble, and synthetic MWFs, as well as duration of exposure to ethanolamines and nitrosamines. Penalized splines were also fit to estimate the functional form of the exposure-response relation. Increased bladder cancer risk was associated with straight MWFs but not with any other exposure. The hazard ratio increased with cumulative exposure to a maximum of 2-fold observed at 75 mg/m(3)-year straight MWF exposure (lagged 20 years). Calendar time windows relevant to polycyclic aromatic hydrocarbon exposure were examined but could not be distinguished from the lagged (10-, 20-year) metrics. No association was observed between any exposure and incident lung cancer, suggesting that smoking is unlikely to confound the associations observed here. The quantitative relation with straight MWFs strengthens the evidence for mineral oils as a bladder carcinogen.

  19. Neoadjuvant paradigm for accelerated drug development: an ideal model in bladder cancer.

    PubMed

    Chism, David D; Woods, Michael E; Milowsky, Matthew I

    2013-01-01

    Neoadjuvant cisplatin-based combination chemotherapy for muscle-invasive bladder cancer (MIBC) has been shown to confer a survival advantage in two randomized clinical trials and a meta-analysis. Despite level 1 evidence supporting its benefit, utilization remains dismal with nearly one-half of patients ineligible for cisplatin-based therapy because of renal dysfunction, impaired performance status, and/or coexisting medical problems. This situation highlights the need for the development of novel therapies for the management of MIBC, a disease with a lethal phenotype. The neoadjuvant paradigm in bladder cancer offers many advantages for accelerated drug development. First, there is a greater likelihood of successful therapy at an earlier disease state that may be characterized by less genomic instability compared with the metastatic setting, with an early readout of activity with results determined in months rather than years. Second, pre- and post-treatment tumor tissue collection in patients with MIBC is performed as the standard of care without the need for research-directed biopsies, allowing for the ability to perform important correlative studies and to monitor tumor response to therapy in "real time." Third, pathological complete response (pT0) predicts for improved outcome in patients with MIBC. Fourth, there is a strong biological rationale with rapidly accumulating evidence for actionable targets in bladder cancer. This review focuses on the neoadjuvant paradigm for accelerated drug development using bladder cancer as the ideal model.

  20. Development and Application of a Microfluidics-Based Panel in the Basal/Luminal Transcriptional Characterization of Archival Bladder Cancers

    PubMed Central

    Foreman, Oded; Tam, Rachel N.; Patel, Rajesh; Schleifman, Erica B.; Motlhabi, Maipelo; French, Dorothy; Wong, Cheryl V.; Peters, Eric; Molinero, Luciana; Raja, Rajiv; Amler, Lukas C.; Hampton, Garret M.; Lackner, Mark R.; Kabbarah, Omar

    2016-01-01

    In the age of personalized medicine stratifying tumors into molecularly defined subtypes associated with distinctive clinical behaviors and predictable responses to therapies holds tremendous value. Towards this end, we developed a custom microfluidics-based bladder cancer gene expression panel for characterization of archival clinical samples. In silico analysis indicated that the content of our panel was capable of accurately segregating bladder cancers from several public datasets into the clinically relevant basal and luminal subtypes. On a technical level, our bladder cancer panel yielded robust and reproducible results when analyzing formalin-fixed, paraffin-embedded (FFPE) tissues. We applied our panel in the analysis of a novel set of 204 FFPE samples that included non-muscle invasive bladder cancers (NMIBCs), muscle invasive disease (MIBCs), and bladder cancer metastases (METs). We found NMIBCs to be mostly luminal-like, MIBCs to include both luminal- and basal-like types, and METs to be predominantly of a basal-like transcriptional profile. Mutational analysis confirmed the expected enrichment of FGFR3 mutations in luminal samples, and, consistently, FGFR3 IHC showed high protein expression levels of the receptor in these tumors. Our bladder cancer panel enables basal/luminal characterization of FFPE tissues and with further development could be used for stratification of bladder cancer samples in the clinic. PMID:27846280

  1. Development and Application of a Microfluidics-Based Panel in the Basal/Luminal Transcriptional Characterization of Archival Bladder Cancers.

    PubMed

    Kim, Doris; Choi, YounJeong; Ireland, James; Foreman, Oded; Tam, Rachel N; Patel, Rajesh; Schleifman, Erica B; Motlhabi, Maipelo; French, Dorothy; Wong, Cheryl V; Peters, Eric; Molinero, Luciana; Raja, Rajiv; Amler, Lukas C; Hampton, Garret M; Lackner, Mark R; Kabbarah, Omar

    2016-01-01

    In the age of personalized medicine stratifying tumors into molecularly defined subtypes associated with distinctive clinical behaviors and predictable responses to therapies holds tremendous value. Towards this end, we developed a custom microfluidics-based bladder cancer gene expression panel for characterization of archival clinical samples. In silico analysis indicated that the content of our panel was capable of accurately segregating bladder cancers from several public datasets into the clinically relevant basal and luminal subtypes. On a technical level, our bladder cancer panel yielded robust and reproducible results when analyzing formalin-fixed, paraffin-embedded (FFPE) tissues. We applied our panel in the analysis of a novel set of 204 FFPE samples that included non-muscle invasive bladder cancers (NMIBCs), muscle invasive disease (MIBCs), and bladder cancer metastases (METs). We found NMIBCs to be mostly luminal-like, MIBCs to include both luminal- and basal-like types, and METs to be predominantly of a basal-like transcriptional profile. Mutational analysis confirmed the expected enrichment of FGFR3 mutations in luminal samples, and, consistently, FGFR3 IHC showed high protein expression levels of the receptor in these tumors. Our bladder cancer panel enables basal/luminal characterization of FFPE tissues and with further development could be used for stratification of bladder cancer samples in the clinic.

  2. Stratifying patients with haematuria into high or low risk groups for bladder cancer: a novel clinical scoring system.

    PubMed

    Hee, Tan Guan; Shah, Shamsul Azhar; Ann, Ho Sue; Hemdan, Siti Nurhafizah; Shen, Lim Chun; Al-Fahmi Abdul Galib, Nurudin; Singam, Praveen; Chee Kong, Christopher Ho; Hong, Goh Eng; Bahadzor, Badrulhisham; Zainuddin, Zulkifli Md

    2013-01-01

    Haematuria is a common presentation of bladder cancer and requires a full urologic evaluation. This study aimed to develop a scoring system capable of stratifying patients with haematuria into high or low risk groups for having bladder cancer to help clinicians decide which patients need more urgent assessment. This cross- sectional study included all adult patients referred for haematuria and subsequently undergoing full urological evaluation in the years 2001 to 2011. Risk factors with strong association with bladder cancer in the study population were used to design the scoring system. Accuracy was determined by the area under the receiver operating characteristic (ROC) curve. A total of 325 patients with haematuria were included, out of which 70 (21.5%) were diagnosed to have bladder cancer. Significant risk factors associated with bladder cancer were male gender, a history of cigarette smoking and the presence of gross haematuria. A scoring system using 4 clinical parameters as variables was created. The scores ranged between 6 to 14, and a score of 10 and above indicated high risk for having bladder cancer. It was found to have good accuracy with an area under the ROC curve of 80.4%, while the sensitivity and specificity were 90.0% and 55.7%, respectively. The scoring system designed in this study has the potential to help clinicians stratify patients who present with haematuria into high or low risk for having bladder cancer. This will enable high-risk patients to undergo urologic assessment earlier.

  3. miR‑485‑5p inhibits bladder cancer metastasis by targeting HMGA2.

    PubMed

    Chen, Zhijun; Li, Qingwen; Wang, Sheng; Zhang, Jiajun

    2015-10-01

    MicroRNA (miRNA or miR)‑485 is a functional miRNA which has received much attention in recent years. However, little is known about the expression of miR‑485 or the role it plays in bladder cancer [namely in metastasis and epithelial‑mesenchymal transition (EMT)]. Thus, in the present study, we aimed to detect the expression of miR‑485 in human bladder cancer tissues and bladder cancer cell lines, and to examine the effects of miR‑485‑5p on bladder cancer cell metastasis and EMT. We found that the expression of miR‑485‑5p was downregulated in the human bladder cancer tissues and different bladder cancer cell lines compared with the normal tissues and cell lines, as demonstrated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). We enforced the expression of miR‑485‑5p in T24 cells and inhibited the expression of miR‑485‑5p in SW780 cells by transfection with miR‑485‑5p mimic or miR‑485‑5p inhibitor, respectively. The ectopic expression of miR‑485‑5p was shown to inhibit cell metastasis and EMT, whereas the inhibition of miR‑485‑5p expression promoted cell metastasis and EMT, as shown by transwell‑matrigel assay, cell adhesion assay and western blot analysis. Furthermore, a luciferase reporter assay revealed that high mobility group AT‑hook 2 (HMGA2) was a direct target of miR‑485‑5p and that the overexpression of HMGA2 reversed the effects of miR‑485‑5p on cell metastasis and EMT. In conclusion and to the very best of our knowledge, the present study, for the first time, identified miR‑485‑5p as a suppressive miRNA in human bladder cancer, and demonstrated that miR‑485‑5p inhibits cell metastasis and EMT at least partly through the suppression of HMGA2 expression.

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

    PubMed

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

    2016-11-01

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

  5. PSCA rs2294008 C > T polymorphism contributes to gastric and bladder cancer risk

    PubMed Central

    Wang, Meng; Wang, Xi-Jing; Ma, Yun-Feng; Ma, Xiao-Bin; Dai, Zhi-Ming; Lv, Ye; Lin, Shuai; Liu, Xing-Han; Yang, Peng-Tao; Dai, Zhi-Jun

    2015-01-01

    Background Previous studies suggested genetic variations in PSCA (prostate stem cell antigen) may confer the susceptibility of cancer. Many case–control studies have reported the relationship between PSCA rs2294008 C > T polymorphism and cancer, especially gastric cancer and bladder cancer. However, the results are inconsistent. This meta-analysis is aimed at evaluating the association of rs2294008 polymorphism with cancer risk. Methods The databases of PubMed, ISI Web of Knowledge, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) were searched for related publications. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of the associations. Fixed models were used when heterogeneity among studies was not detected, otherwise the random model was used. Results Twenty-six studies from 24 articles with 30,050 multiple cancer cases and 51,670 controls were pooled into this meta-analysis. The results showed that the rs2294008 polymorphism was associated with increased cancer risk in any genetic model (T vs C, OR: 1.18, 95% CI: 1.08–1.28; TT vs CC, OR: 1.36, 95% CI: 1.14–1.62; TC vs CC, OR: 1.29, 95% CI: 1.17–1.44; TT + TC vs CC, OR: 1.32, 95% CI: 1.18–1.49; TT vs TC + CC, OR: 1.15, 95% CI: 1.02–1.30). In stratified analysis by cancer type, we found that the T allele had a significant high risk of gastric and bladder cancer, but not in other cancers. In subgroup analysis by ethnicity, increased cancer risk was found in both Asians and Caucasians. Conclusion Our study suggested that the PSCA rs2294008 C > T polymorphism is a risk factor for cancer, especially in gastric and bladder cancer. PMID:25709466

  6. Inhibition of T24 and RT4 Human Bladder Cancer Cell Lines by Heterocyclic Molecules

    PubMed Central

    Zhao, Zhi-Feng; Wang, Kai; Guo, Feng-Fu; Lu, Hua

    2017-01-01

    Background Bladder cancer is a major widespread tumor of the genitourinary tract. Around 30% of patients with superficial cancers develop invasive and metastatic pathology. Material/Methods Some new heterocyclic 4-methyl coumarin derivatives were designed using molecular modeling studies to evaluate their potential against bladder cancer lines T24 and RT-4. The designed compounds that showed good binding affinity to T24 and RT4 were synthesized, with excellent yield. The synthesized compounds after structural evaluation were further evaluated for their antiproliferative activity by cell viability assay, cell cycle analysis, and apoptosis assay. Results The compound BC-14 exhibited the best cytotoxicity against T24 cells, but were not highly active against RT4 cells. Conclusions The results of the present study may suggest the selectivity pattern of the synthesized compounds. These results should be explored further with chemical modification for other cancer types. PMID:28260746

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

    NASA Astrophysics Data System (ADS)

    Dewi, C.; Trisilowati

    2015-03-01

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

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

    PubMed

    Aragon-Ching, Jeanny B; Trump, Donald L

    2016-09-01

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

  9. The effects of visual fluorescence marking induced by 5-aminolevulinic acid for endoscopic diagnosis of urinary bladder cancer

    NASA Astrophysics Data System (ADS)

    Daniltchenko, Dmitri I.; Koenig, Frank; Schnorr, Dietmar; Valdman, Alexander; Al-Shukri, Salman; Loening, Stefan A.

    2003-10-01

    During cystoscopy procedure, fluorescence diagnostics induced by 5-ALA improves visual detection of the bladder cancer. Macroscopic ALA-fluorescence allows visualizing of small flat tumors, carcinoma in situ, true neoplasm margins and dysplasias of the bladder. Following ALA instillation, cystoscopy has been performed under both standard and blue light illumination. Totally, 153 biopsies have been carried out at 53 patients with suspicion of bladder cancer. The results were compared to ALA-fluorescence data. In 13% of the patients, bladder cancer and dysplasia were found out in addition, due to red fluorescence. The sensitivity and specificity of ALA-fluorescence technique aggregated 96% and 52% respectively. The sensitivity and specificity of 5-ALA-fluorescent detection exceeded standard endoscopy under white light on 20%. The new method does not exclude a false positive and a false negative fluorescent luminescence. The ALA-based fluorescence detection system enhances the diagnosis of malignant/dysplastic bladder lesions significantly.

  10. Electroporation enhances mitomycin C cytotoxicity on T24 bladder cancer cell line: a potential improvement of intravesical chemotherapy in bladder cancer.

    PubMed

    Vásquez, Juan L; Gehl, Julie; Hermann, Gregers G

    2012-12-01

    Intravesical mitomycin instillation combined with electric pulses is being used experimentally for the treatment of T1 bladder tumors, in patients unfit for surgery. Electroporation may enhance the uptake of chemotherapeutics by permeabilization of cell membranes. We investigated if electroporation improves the cytotoxicity of mitomycin. In two cell lines, T24 (bladder cancer cell line) and DC3F (Chinese hamster fibroblast), exposure to different concentrations of mitomycin (0.01-2000μM) was tested with and without electroporation (6 pulses of 1kV/cm, duration: 99μs, frequency: 1Hz). Cell viability was assessed by colorimetric assay (MTT). For both cell lines, mitomycin's IC_50 was approximately 1000μM in both pulsed and unpulsed cells. On T24 cells, electroporation and mitomycin caused (relative reduction) RR of survival of: 25%, 31% and 29%, by concentrations 0μM, 500μM and 1000μM respectively. For DC3F cells, the RRs of survival were: 28%, 29%, and 33%, by concentrations 0μM, 500μM and 1000μM respectively. In conclusion, electroporation and mitomycin together are about 30% more effective than mitomycin alone. The results help to elucidate the additive effect of mitomycin and electric pulses and support the use of this combination in the treatment of bladder cancer.

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

    PubMed Central

    Ceci, Claudia; Tentori, Lucio; Atzori, Maria Grazia; Lacal, Pedro M.; Bonanno, Elena; Scimeca, Manuel; Cicconi, Rosella; Mattei, Maurizio; de Martino, Maria Gabriella; Vespasiani, Giuseppe; Miano, Roberto; Graziani, Grazia

    2016-01-01

    Ellagic acid (EA) is a polyphenolic compound that can be found as a naturally occurring hydrolysis product of ellagitannins in pomegranates, berries, grapes, green tea and nuts. Previous studies have reported the antitumor properties of EA mainly using in vitro models. No data are available about EA influence on bladder cancer cell invasion of the extracellular matrix triggered by vascular endothelial growth factor-A (VEGF-A), an angiogenic factor associated with disease progression and recurrence, and tumor growth in vivo. In this study, we have investigated EA activity against four different human bladder cancer cell lines (i.e., T24, UM-UC-3, 5637 and HT-1376) by in vitro proliferation tests (measuring metabolic and foci forming activity), invasion and chemotactic assays in response to VEGF-A and in vivo preclinical models in nude mice. Results indicate that EA exerts anti-proliferative effects as a single agent and enhances the antitumor activity of mitomycin C, which is commonly used for the treatment of bladder cancer. EA also inhibits tumor invasion and chemotaxis, specifically induced by VEGF-A, and reduces VEGFR-2 expression. Moreover, EA down-regulates the expression of programmed cell death ligand 1 (PD-L1), an immune checkpoint involved in immune escape. EA in vitro activity was confirmed by the results of in vivo studies showing a significant reduction of the growth rate, infiltrative behavior and tumor-associated angiogenesis of human bladder cancer xenografts. In conclusion, these results suggest that EA may have a potential role as an adjunct therapy for bladder cancer. PMID:27879653

  12. Meta-analysis of studies on individual consumption of chlorinated drinking water and bladder cancer

    PubMed Central

    Villanueva, C; Fernandez, F; Malats, N; Grimalt, J; Kogevinas, M

    2003-01-01

    Design: A bibliographic search was conducted and the authors selected studies evaluating individual consumption of chlorinated drinking water and bladder cancer. The authors extracted from each study risk estimates for intermediate and long term (>40 years) consumption of chlorinated water, stratified by sex when possible, and performed meta-analysis for the two exposure levels. A meta-analysis was also performed of the dose-response regression slopes. Setting: Populations in Europe and North America. Participants: Those included in six case-control studies (6084 incident bladder cancer cases, 10 816 controls) and two cohort studies (124 incident bladder cancer cases) fulfilling the inclusion criteria. Main results: Ever consumption of chlorinated drinking water was associated with an increased risk of bladder cancer in men (combined OR=1.4, 95%CI 1.1 to 1.9) and women (combined OR=1.2, 95%CI 0.7 to 1.8). The combined OR for mid-term exposure in both genders was 1.1 (95% CI 1.0 to 1.2) and for long term exposure was 1.4 (95%CI 1.2 to 1.7). The combined estimate of the slope for a linear increase in risk was 1.13 (95% CI 1.08 to 1.20) for 20 years and 1.27 (95% CI 1.15 to 1.43) for 40 years of exposure in both sexes. Conclusions: This meta-analysis of the best available epidemiological evidence indicates that long term consumption of chlorinated drinking water is associated with bladder cancer, particularly in men. The observed relative risk is only moderately high, but the population attributable risk could be important as the vast majority of the population of industrialised countries is potentially exposed to chlorination byproducts for long time periods. PMID:12594192

  13. Relationship between bladder cancer and total fluid intake: a meta-analysis of epidemiological evidence

    PubMed Central

    2014-01-01

    Objectives Epidemiological findings regarding the association between total fluid intake and bladder cancer risk have yielded varying results. Our objective is to examine the possible associations between total fluid intake and bladder cancer risk. Methods Databases searched include the EMBASE and PUBMED, from inception to February 2014, with no limits on study language. We also reviewed the reference lists of identified studies. Stratified analyses were performed. A random-effect model was used to summarize the estimates of odds ratio (OR) with 95% confidence intervals (CI). Results Overall,17 case-control and four cohort studies were included. The overall OR of bladder cancer for the highest versus the lowest fluid intake was 1.06 (95% CI: 0.88-1.27). In the subgroup analyses, the overall ORs for coffee, green, and black tea intake were 1.17 (95% CI: 1.03-1.33), 0.76 (95% CI: 0.66-0.95), and 0.80 (95% CI: 0.65-0.97), respectively. A significantly decreased risk was observed in Asian people (OR 0.27; 95% CI: 0.10-0.72). Among smokers, a suggestive inverse association was observed between total fluid intake and overall bladder cancer risk (OR 0.80; 95% CI: 0.62-1.02). Conclusions Although this meta-analysis suggested that greater consumption of fluid may have a protective effect on bladder cancer in Asian people, there was no convincing evidence on this association because of the limitations of the individual trials. PMID:25033957

  14. Local Bladder Cancer Clusters in Southeastern Michigan Accounting for Risk Factors, Covariates and Residential Mobility

    PubMed Central

    Jacquez, Geoffrey M.; Shi, Chen; Meliker, Jaymie R.

    2015-01-01

    Background In case control studies disease risk not explained by the si