Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005684 (bladder cancer)
 16,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor recurrence is a hallmark of superficial bladder cancer. Currently, a molecular marker for bladder cancer recurrence is lacking. E-cadherin plays an important role in epithelial development and in the establishment and maintenance of cell-cell adhesion and tissue architecture. The purpose of this study is to investigate the association of an E-cadherin promoter polymorphism (CDH1c-160a) with the risk of bladder cancer recurrence. This study included 302 patients with superficial bladder cancer. Genomic DNA was extracted from peripheral blood lymphocytes and genotyping was performed using Taqman assay. Clinical data were collected by medical chart review. Cox proportional hazard model was used to estimate the hazard ratios (HRs) associated with genotypes while adjusting for age, gender, smoking status, tumor stage and grade where appropriate. During a median follow-up of 27.65 months, 151 patients experienced disease recurrence. Subsequent analyses were restricted to Caucasians only due to the small sample size of other ethnic groups (13 in recurrence group and 15 in non-recurrence group). Among the 274 Caucasian patients, 138 developed recurrence during the same length of follow-up time. In Caucasian patients, having at least one variant A allele conferred a 32% reduction in recurrence risk (adjusted HR: 0.68; 95% CI: 0.48-0.96). The median recurrence-free survival for patients carrying at least one variant A allele was significantly longer than that for patients with a homozygous CC genotype (40.4 vs 12.5 months, p=0.04). Our findings suggest that the E-cadherin promoter polymorphism may be a valuable molecular marker for bladder cancer recurrence.
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PMID:E-cadherin promoter polymorphism (C-160A) and risk of recurrence in patients with superficial bladder cancer. 1692 27

An alteration in the expression of E-cadherin has been observed in many epithelial neoplasms. No data exist, however, for the expression of this protein in an animal model for urinary bladder cancer. The present study investigated the expression of E-cadherin in rat urothelial preneoplastic lesions and tumours induced by oral administration of N-butyl-N-(4-hydroxybutyl) nitrosamine, during 10, 15 and 20 weeks. Simple hyperplasia and squamous metaplasia showed a similar E-cadherin pattern when compared with normal urothelium, with its expression confined to cell membrane. Thirty eight percent of the nodular hyperplasia, 41.4% of the dysplasia and 100% of the papillomas showed a weak E-cadherin expression. All papillary neoplasm of low malignant potential, low-and high-grade papillary carcinoma, and invasive carcinoma revealed an abnormal staining pattern with an increase in cytoplasm reactivity and discontinuous cell membrane positivity. The loss of expression for low-grade papillary carcinoma versus simple hyperplasia, nodular hyperplasia and dysplasia was statistically significant (p = 0.0001, p = 0.007 and p=0.008, respectively). There was a similar decrease in E-cadherin expression for papillary neoplasm of low malignant potential versus simple hyperplasia, nodular hyperplasia and dysplasia (p = 0.0001; p = 0.001 and p=0.0001, respectively). These results suggest that alteration in the expression of this adhesion molecule in rat may be indicative of tumour progression in N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder cancer.
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PMID:E-cadherin expression during urothelial carcinogenesis induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in rats. 1716 84

We characterized the effects of the small molecule epidermal growth factor receptor (EGFR) inhibitor gefitinib (ZD1839, Iressa) on cell proliferation in a panel of 17 human bladder cancer cell lines. Gefitinib inhibited DNA synthesis in a concentration-dependent fashion in 6 of 17 lines. Growth inhibition was associated with p27(Kip1) accumulation and decreased cyclin-dependent kinase 2 activity. Gefitinib also inhibited baseline EGFR, AKT, and extracellular signal-regulated kinase (ERK) phosphorylation in the EGFR-dependent cells maintained in serum-free medium, whereas it had no effect on baseline EGFR or ERK phosphorylation in the EGFR-independent cells. Analyses of candidate markers of EGFR dependency revealed that the gefitinib-sensitive cells expressed higher surface EGFR levels than the gefitinib-resistant lines. Gefitinib-sensitive cells generally expressed higher levels of E-cadherin and lower levels of vimentin than the gefitinib-resistant cells, but these correlations were not perfect, suggesting that these markers of epithelial-mesenchymal transition cannot be used by themselves to prospectively predict EGFR-dependent growth. Together, our results show that bladder cancer cells are markedly heterogeneous with respect to their sensitivity to EGFR antagonists. Although surface EGFR levels and epithelial-mesenchymal transition status seem to roughly correlate with responsiveness, they cannot be used by themselves to identify bladder tumors that will be sensitive to EGFR-directed therapy. However, comparing levels of p27(Kip1) or DNA synthesis before and after gefitinib exposure does identify the drug-sensitive cells.
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PMID:Molecular correlates of gefitinib responsiveness in human bladder cancer cells. 1723 87

Recently, TWIST, a basic helix-loop-helix transcription factor, has been reported to play a key role in the metastatic progression of several types of human cancer. The aim of this study was to investigate the significance of TWIST expression in bladder cancer using tissue microassays generated from 226 bladder tissue specimens. Using immunohistochemical staining, we studied TWIST expression levels in nonmalignant bladder tissues (n = 37), primary bladder cancer tissues (n = 164), and 25 cases of matched lymph node metastatic lesions. The association between TWIST expression levels and tumor staging and grading, as well as metastatic potential, was analyzed by statistical analysis. Our results showed that TWIST protein expression was significantly higher in bladder cancer specimens compared with nonmalignant tissues (P < .001), indicating its positive role in the development of bladder cancer. In addition, increased TWIST expression levels were associated with advanced-stage and high-grade tumors, suggesting its involvement in the progression of this cancer. Furthermore, TWIST expression was much higher in the metastatic lesion compared with its primary site (P < .05). More importantly, the increased TWIST expression in bladder cancer specimens was correlated with decreased membranous expression of E-cadherin, a cell adhesion molecule that plays a key role in the metastatic progression of human cancer. Our results demonstrate TWIST as a novel positive factor in the development and progression of bladder cancer and suggest a marker for advanced bladder cancer.
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PMID:Significance of TWIST expression and its association with E-cadherin in bladder cancer. 1725 91

The protein structure of human tumor tissue has a significant influence on the molecular attributes. It was demonstrated that the individual prognosis of tumor patients is among other things dependent on molecular tumor tissue characteristics.A promising marker is E-cadherin, an adhesion glycoprotein which plays a central role in the mediation of cell-cell contacts. Aberrant E-cadherin expressions were described in several tumors such as in bladder cancer. This was also found to be correlated with tumor invasion and survival. There are hardly any fast, quantitative and easily automated protein assays in everyday practice which can analyze several markers at the same time. With silicon chip technology we have a new detection and measurement method which makes it possible to give a quantitative analysis of numerous different proteins in tissue, urine, or serum in a few minutes.
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PMID:[Use of silicon chip technology to detect protein-based tumor markers in bladder cancer]. 1759 36

The objective of this study is to determine whether trichostatin A (TSA) can suppress the invasiveness of 2 endometriotic cell lines known to be invasive and E-cadherin negative. The membrane invasion culture system was used to assess cell invasion using invasive and a noninvasive bladder cancer cell lines as positive and negative controls, respectively. The E-cadherin mRNA levels and protein expression were evaluated by real-time reverse transcriptase polymerase chain reaction and Western blot analysis, respectively. The authors found that TSA attenuates the invasiveness of 2 cell lines in the presence or absence of tumor necrosis factor alpha (TNFalpha) stimulation. In addition, TSA treatment reactivates E-cadherin gene and protein expression in these cell lines. These results, along with recent findings that TSA suppresses proliferation, interleukin-1 beta-induced cyclo-oxygenase 2 expression, and constitutive or TNFalpha-stimulated nuclear factor kappa B activation in endometrial and endometriotic cells, makes histone deacetylase inhibitors a promising class of compounds for novel and more effective medical treatment of endometriosis, especially given the mounting evidence that endometrios be an epigenetic disease.
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PMID:Trichostatin A, a histone deacetylase inhibitor, attenuates invasiveness and reactivates E-cadherin expression in immortalized endometriotic cells. 1764 10

Upper tract urothelial carcinoma (UTUC) is uncommon relative to primary bladder transitional cell carcinoma, with notable differences at the genetic, molecular and clinical levels. A variety of management options with similar oncologic outcomes are available for UTUC. Regardless of upper tract treatment modality, recurrence in the bladder consistently occurs in 20-50% of patients, thus presenting a significant clinical challenge. The initial intravesical relapse typically occurs within the first 2 years following upper tract therapy, but the risk is lifelong and repeat episodes are common. The identification of variables that allow accurate risk stratification of UTUC patients with regards to future bladder relapse is crucial. Unfortunately, to date, no variables have been identified that can reliably predict such bladder recurrences. A history of bladder cancer prior to UTUC resection and upper tract tumor multifocality are frequently reported clinical risk factors. Candidate molecular markers, such as E-cadherin, also hold promise for improving patient risk stratification. The impact of bladder recurrences on patient survival is still poorly defined. The risk of progression to invasive bladder disease is not well documented but appears to be an infrequent event. This article highlights important recent observations and key current issues regarding UTUC and subsequent bladder cancer. In addition, we suggest a bladder surveillance regimen following UTUC and provide recommendations for managing patients with intravesical recurrences.
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PMID:Bladder cancer following upper tract urothelial carcinoma. 1809 85

Bladder cancer is the fifth most common malignancy in the UK. Clinically, the most important process in determining prognosis is the development of invasion, initially of the lamina propria and then beyond as these transitional cell carcinomas (TCCs) progress from stage pT1 to stages T2+. Cadherins and catenins are the main mediators of cell-cell interactions in epithelial tissues, and loss of membranous E-cadherin immunoreactivity is strongly correlated with high grade, advanced stage and poor prognosis in bladder cancer and other malignancies. However, the role of P-cadherin is yet to be fully elucidated in bladder TCC. The objectives of this study were to establish how the expression of cadherins and catenins determines clinical and in vitro behaviour in bladder TCC. Utilizing immunohistochemistry, immunofluorescence and western blotting, we demonstrated a significant reduction in the expression of E-cadherin and beta-catenin as grade and stage of bladder TCC progress, accompanied by a significant increase in P-cadherin expression (all p < 0.05, Pearson's chi2 test). Increased P-cadherin expression was also associated with a significantly worse bladder cancer-specific survival (log rank p = 0.008), with Cox regression showing P-cadherin to be an independent prognostic factor. Utilizing a variety of tissue culture models in a range of functional studies, we demonstrated that P-cadherin mediates defective cell-cell adhesion and enhances anchorage-independent growth. The results provide evidence that increased P-cadherin expression promotes a more malignant and invasive phenotype of bladder cancer, and appears to have a novel role late in the disease.
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PMID:Cadherin switching dictates the biology of transitional cell carcinoma of the bladder: ex vivo and in vitro studies. 1839 67

Recent studies have reported that chemically synthesized small duplex RNAs complementary to promoters of target genes can specifically induce gene expression in several cancer cell lines. Such dsRNA, referred to as small activating RNA (saRNA), are involved in the recently described phenomenon called RNA activation (RNAa). Recent findings show that saRNA can inhibit cell proliferation and viability via up-regulation of p21(WAF1/CIP1) (p21) in human bladder cancer cells. In the present study, we demonstrate that induction of E-cadherin expression by saRNA leads to suppression of migration and invasion of 5637 human bladder cancer cells in vitro. The elevated E-cadherin expression was confirmed at transcriptional and protein levels after transfection of a 21-nucleotide dsRNA targeting the E-cadherin promoter (dsEcad). Furthermore, this inhibitory effect was associated with relocalization of beta-catenin from the nucleus to the plasma membrane and decreased beta-catenin-mediated transactivation. These data suggest that activation of E-cadherin by saRNA may have a therapeutic benefit for bladder and other types of cancer.
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PMID:Up-regulation of E-cadherin by small activating RNA inhibits cell invasion and migration in 5637 human bladder cancer cells. 1872 95

We report a rare case of plasmacytoid urothelial carcinoma (PUC) of the urinary bladder. A 50-year-old man complained of pollakiuria and urinary incontinence. MRI detected a bladder tumor invading the rectum and bilateral hydroureteronephrosis. Radical cystectomy with partial resection of the rectum was performed, and ileus due to peritoneal dissemination occurred 2 years after surgery. He died of the disease 42 months after the initial presentation. Histologically, urothelial carcinoma in situ with a focal invasive urothelial carcinoma (IUC) component and widely spread PUC was observed. There was no lymph node metastasis. PUC cells had eccentrically placed nuclei and eosinophilic cytoplasm resembling plasmacytoma cells, and proliferated with a single-cell infiltrative pattern to the outside of the bladder. IUC cells with intracytoplasmic lumina were focally intermingled with PUC cells. Immunohistochemically, PUC cells were positive for cytokeratin 7, epithelial membrane antigen, and CA19-9, but negative for cytokeratin 20, E-cadherin, p63, and lymphoid markers. The Ki-67 labeling index of PUC cells was 9.3%. IUC containing intracytoplasmic lumina showed intermediate features of conventional IUC and PUC morphologically and immunohistochemically. PUC is a distinct entity of bladder cancer with a high propensity for invasion and poor prognosis.
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PMID:Plasmacytoid urothelial carcinoma of the urinary bladder: a case report and immunohistochemical study. 1904 Nov 93


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