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Query: UMLS:C0005684 (bladder cancer)
 16,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of EGF and gefitinib on two EGFR-positive human bladder cancer cell lines has been investigated using array-based gene expression profiling. The most prominent transcript, increased up to 6.7-fold by EGF compared with controls in RT112 cells, was human early growth response protein 1 (hEGR1). This induction was prevented by gefitinib. The hEGR1 mRNA in EGF-treated samples was reduced in the presence of gefitinib, as was hEGR1 protein in cell lysates. In the RT4 cells, hEGR1 expression was halved in the presence of EGF and gefitinib in combination. In bladder tumour samples, there was a significant correlation between hEGR1 mRNA detected by RT-PCR and EGFR detected by ligand binding, (P=0.042). The induction by EGF of the hEGR1 gene, mRNA and protein in RT112 cells, and its inhibition by gefitinib, together with the detection of hEGR1 mRNA in bladder tumours, suggests that hEGR1 may be important in the EGFR growth-signalling pathway in bladder cancer and should be further investigated for its prognostic significance and as a potential therapeutic target.
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PMID:hEGR1 is induced by EGF, inhibited by gefitinib in bladder cell lines and related to EGF receptor levels in bladder tumours. 1731 Oct 25

In the majority of cases, death from bladder cancer results from metastatic disease. Understanding the closely linked mechanisms of invasion, metastasis and angiogenesis in bladder cancer has allowed us to develop new therapeutic strategies that harbor the promise of decisive improvements in patient survival. The essential link between cell based experiments and the translation of novel agents into human patients with bladder cancer is the animal model. With emphasis on the orthotopic xenograft model, this review outlines some key mechanisms relevant to angiogenesis and the development of metastasis in bladder cancer. We highlight especially pathways related to MMP-9, IL-8, VEGF and EGFR. Most commonly, expression patterns of these markers in patients have correlated to disease progression and patient survival, which has led to laboratory investigations of these markers and eventually novel targeted therapies that are translated back into the clinic by means of clinical trials. Although imperfect in their translatability into clinical efficacy, animal models remain a critical tool in bladder cancer research.
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PMID:Bladder cancer angiogenesis and metastasis--translation from murine model to clinical trial. 1772 80

Advanced bladder/urothelial cancer remains an incurable terminal disease, and accounts for 3% of the cancer related mortality in the United States. Systemic chemotherapy achieves palliation, survival benefit, and occasional long-term remissions. The two regimens that have been widely adopted consist of either cisplatin and gemcitabine, or the MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) regimen. Novel therapies are being evaluated in metastatic bladder cancer to improve survival outcomes. A randomized trial of larotaxel (a novel taxane) and cisplatin vs cisplatin and gemcitabine in frontline therapy of metastatic urothelial cancer is ongoing. The studies evaluating therapies targeted frontline involve cisplatin and gemcitabine with or without cetuximab (ongoing), and with or without bevacizumab (CALGB proposed trial). With the advent of adjuvant/neoadjuvant cisplatin-based therapy, and improvement in supportive care, more patients are being considered for second-line therapies in urothelial cancer thus making this a field of emerging importance. The only phase III trial in pretreated urothelial cancer compared vinflunine with best supportive care, and revealed no significant survival improvement. Clinical trials are ongoing with pazopanib, a VEGF inhibitor, and Zactima, a VEGF and EGFR inhibitor. The biggest hurdle to progress in advanced bladder cancer has been the slow accrual to studies in the United States. Making clinical trial participation a priority in bladder cancer is the dire need of the moment. At the same time, it is essential to take into account the changing needs of the population afflicted with bladder cancer, and tailor the therapeutic trials to fit a contemporary patient.
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PMID:Systemic therapy of advanced urothelial cancer. 1940 29

The Ras-MAPK pathway is important to orchestrating a cell's response to external and internal stimuli. This pathway is commonly dysregulated in cancer, including bladder cancer. Multiple components of this complex pathway have been identified as potential targets for drug development. After initial preclinical studies many drugs targeting the Ras-MAPK pathway are being studied in phase II clinical trials for advanced bladder cancer either alone or in combination with other chemotherapeutic agents. Drugs presently in clinical trials inhibit the tyrosine kinases, including FGFR, EGFR, ERBB2, and PDGF, either through small molecule tyrosine kinase, dual kinase or farnesyltransferase inhibitors. Recent drug patents targeting the Ras-MAPK pathway in cancer are becoming more selective with the potential for improved therapeutic response and better toxicity as compared to the more universal MAPK pathway inhibitors. In the present review we summarize the importance of the Ras-MAPK pathway in cancer with a focus on bladder cancer and discuss current drugs and recent patents (2004-2008) that target this important pathway in bladder cancer.
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PMID:Ras-MAPK pathway as a therapeutic target in cancer--emphasis on bladder cancer. 1951 35

Principally there are two different types of bladder cancer. Non-invasive papillary low grade tumors (pTa G1-G2) are genetically stable, recur frequently but show a low risk of progression. On the other hand there are high grade tumors (pT1-4, carcinoma in situ), which are genetically unstable, show biologically aggressive behaviour and progress. The distinction between non-invasive (pTa) and minimal-invasive (pT1) is one of the most challenging areas in bladder pathology. Due to the lack of appropriate auxiliary analysis the diagnosis is based entirely on histopathology. P53 immunohistochemistry can be helpful in the assessment of recurring high grade neoplasia. Targeted therapy in bladder cancer is particularly interesting, since a high number of oncogenes are activated and overexpressed (e.g. HER2 and EGFR).
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PMID:[Tumors of the urinary system. Current and old problems]. 1996 Feb 99

Since the advent of cisplatin-based chemotherapy, cytotoxic combination chemotherapy remains the mainstay of treatment for locally advanced and metastatic urothelial malignancies. The current paradigm of combining novel agents with cytotoxic chemotherapy without any understanding of the underlying biology of urothelial cancer has limited the impact of developing novel agents for this disease. Current research investigating the biology of bladder cancer, including the role of p53, EMT, EGFR-related pathways, and anti-angiogenic pathways, may potentially impact the future development of novel agents targeting urothelial malignancies. Additionally, the use of novel gene therapy to mediate enhanced interferon expression in the bladder using adenoviral vectors, and enhancing tumor recognition strategies using the immune system with vaccines and anti-CTLA4 antibodies, are of interest. It is hoped that through these efforts we may soon move beyond the traditional cytotoxic chemotherapy paradigm, developing combinations that are more active and less toxic for all patients with urothelial cancer.
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PMID:Bladder cancer: can we move beyond chemotherapy? 2044 67

Cisplatin-based chemotherapy (MVAC : cisplatin, methotrexate, adriamycin, vinblastine ; or GC : cisplatin, gemcitabine) has been the standard of care for patients with advanced urothelial tumor during the last twenty years. Greater knowledge in the molecular biology of bladder cancer lead to the identification of promising target such as EGFR, HER2, or VEGF-VEGFR pathways. The role of targeted therapies as monotherapy, in combination with chemotheray or as maintenance post-chemotherapy is currently under study.
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PMID:[Bladder cancer and new drugs]. 2053 89

The present study investigated the effect of VEGFR and EGFR inhibition via vandetanib (Zactima) on epithelial-mesenchymal transition (EMT) in bladder cancer. Markers of EMT (EGFR, VEGR, E-cadherin and vimentin) were interogated by Western blotting at baseline and after treatment with EGF, VEGF, vandetanib, cisplatin, or their combination using representative epithelial- and mesenchymal-type human bladder cancer cells. Morphological changes induced by these treatments were examined by microscopy over various time courses. The effect of these changes on cisplatin chemotherapy sensitivity was assessed by MTT assay. RT4 and HTB3 cells had epithelial features while CRL1749 and J82 cells had mesenchymal features. After treatment with EGF, the epithelial-type cells demonstrated increased intercellular separation and pseudopodia, with these changes blocked by vandetanib. In contrast, the mesenchymal cells did not exhibit any morphological changes with the EGF treatment but adopted a clustered/epithelial appearance after the administration of vandetanib. Western blotting shows that treatment of epithelial cells with vandetanib increased the expression of E-cadherin. In comparison, mesenchymal cells demonstrated decreased vimentin expression with the treatment of vandetanib in the presence of EGF and VEGF. Improved growth inhibition was seen in the epithelial cells but not in mesenchymal cells with the concurrent treatment of vandetanib and cisplatin. Sequential treatment of mesenchymal cells with vandetanib followed by cisplatin demonstrated synergy with improved cisplatin activity. The findings offer a novel role of vandetanib on the EMT in bladder cancer, providing insight into EMT in bladder cancer.
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PMID:VEGFR and EGFR inhibition increases epithelial cellular characteristics and chemotherapy sensitivity in mesenchymal bladder cancer cells. 2081 84

There are no reliable criteria to handle disease progression of muscle invasive bladder cancer (MIBC), which strongly influences patient survival. Therefore, an accurate predicting method to identify progressive MIBC patients is greatly needed. The aim of this study was to identify a genetic signature associated with disease progression in MIBC. To address this issue, we analyzed three independent cohorts (a training set, test set 1 and test set 2) comprising a total of 128 MIBC patients. Microarray gene expression profiling, including gene network analysis, was performed in the training set to identify a gene expression signature associated with disease progression. The prognostic value of the signature was validated in test set 1 and test set 2 by microarray and real-time reverse transcriptase polymerase chain reaction (RT-PCR), respectively. The determination of gene expression patterns by microarray data analysis identified 1,320 genes associated with disease progression. Gene network analysis of the 1,320 genes suggested that IL1B, S100A8, S100A9 and EGFR were important mediators of MIBC progression. We validated this putative four-gene signature in two independent cohorts (log-rank test, P < 0.05 each, respectively) and estimated the predictive value of the signature by multivariate Cox regression analysis (hazard ratio [HR], 6.24; 95% confidence interval [CI], 1.58-24.61; P = 0.009). Finally, signature-based stratification demonstrated that the four-gene signature was an independent predictor of MIBC progression. In conclusion, a molecular signature defined by four genes represents a promising diagnostic tool for the identification of MIBC patients at high risk of progression.
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PMID:A four-gene signature predicts disease progression in muscle invasive bladder cancer. 2130 47

The expression of EGFR and p53 has not been adequately studied as a prognostic tool in urinary bladder tumors. We analyzed 74 bladder cancer samples from Egypt for EGFR and p53 expression using immunohistochemistry. The tumors were of different histological types, grades and clinical stages, and with established lymph node status. Almost 61% of the tumors showed positive membranous EGFR expression and 74.3% had positive nuclear staining of p53. Analysis of correlation of the IHC staining with clinical variables showed a significant correlation only between EGFR expression and histological type (p=0.002, ANOVA), in that the expression was higher in squamous cell carcinomas than in other histological types. There were no significant correlations between p53 or EGFR with the other clinicopathological variables, including age, sex, staging, grading, and lymph node status. Further studies are needed to determine if EGFR and p53 might be used as prognostic tools in bladder cancer.
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PMID:The Potential Value of EGFR and P53 Immunostaining in Tumors of the Urinary Bladder. 2148 37


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