Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bladder cancer is a model tumor progressing from superficial to locally invasive and finally metastatic disease. The likelihood of progression is determined to a large extent by the molecular profile of the tumor. From the pre-genomic era only p53 emerged as the molecular prognostic factor able to add value to existing clinical and pathological features of bladder cancer, however it was not introduced to the clinic. Microarray technologies enable us to study expression of thousands of genes in the tumor tissue. This method has already proven to add information to clinical classifiers, to find new tumor suppressor genes and to define p53 related pathways of cell-cycle regulation. In the last decade, progress in the treatment of locally invasive and metastatic bladder cancer was minimal; large Phase III trials with neo/adjuvant chemotherapy were inconclusive. The new paradigm of treatment tailored to an individual patient could be realized in bladder cancer for his chronic clinical course with opportunities to obtain tumor samples for microarray studies. Molecular profiling of two samples taken at the superficial stage and at cystectomy should enable us to study the microevolution of the tumor, to tailor existing treatment options, and to introduce new biologicals to the clinic.Introduction
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PMID:From microarrays to new therapeutic approaches in bladder cancer. 1260 52

Over 50,000 patients are diagnosed annually with bladder cancer, and approximately 10,000 eventually will die of their disease. Thus, the Southwest Oncology Group (SWOG) Genitourinary Cancer Committee is committed to the study of therapeutic interventions in patients with superficial, invasive, and metastatic bladder cancer. In the past 15 years, SWOG has completed six Phase III, randomized trials. Studies in patients with superficial disease have established the role of bacillus Calmette-Guerin in patient management; and a large, randomized trial has outlined the value of neoadjuvant chemotherapy and cystectomy in patients with advanced disease. SWOG plans to build on this model by evaluating patients with residual disease after chemotherapy for possible bladder preservation while evaluating more chemotherapy for patients with persistent disease. The Genitourinary Cancer Committee will continue to seek new, active agents for metastatic disease and will participate in and support large, Phase III, international trials that seek to improve current regimens. SWOG accomplishments in bladder cancer are highlighted, and future strategies are discussed.
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PMID:Southwest Oncology Group studies in bladder cancer. 1267 2

Bladder cancer is the fifth most common malignancy in Europe and the fourth most common malignancy in the United States. It affects one in 4000 people and accounts for 5% of all diagnosed cancers. The peak incidence is in the fifth and seventh decade. There is a strong association between smoking and bladder cancer. Smokers have a fourfold higher incidence of developing bladder cancer than the general population. The disease has a spectrum of clinical severity varying from superficial bladder cancer to muscle invasive or metastatic disease which carries a poor prognosis. Currently the superficial form of the disease is managed by endoscopic resection of the tumour, often followed by the instillation into the bladder of cytotoxic agents. Due to the tendency of bladder cancer to recur repeated cystoscopies and resections are often required. Because of this, one of the main thrusts of research is to find a way of preventing the progression from superficial disease to muscle invasive and metastatic bladder cancer.
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PMID:Cancers of the bladder. 1549 83

Half of patients treated for locally advanced bladder cancer relapse with often fatal metastatic disease to the lung. We have recently shown that reduced expression of the GDP dissociation inhibitor, RhoGDI2, is associated with decreased survival of patients with advanced bladder cancer. However, the effectors by which RhoGDI2 affects metastasis are unknown. Here we use DNA microarrays to identify genes suppressed by RhoGDI2 reconstitution in lung metastatic bladder cancer cell lines. We identify such RNAs and focus only on those that also increase with tumor stage in human bladder cancer samples to discover only clinically relevant targets of RhoGDI2. Levels of endothelin-1 (ET-1), a potent vasoconstrictor, were affected by both RhoGDI2 reconstitution and tumor stage. To test the hypothesis that the endothelin axis is important in lung metastasis, lung metastatic bladder carcinoma cells were injected in mice treated with the endothelin receptor-specific antagonist, atrasentan, thereby blocking engagement of the up-regulated ET-1 ligand with its cognate receptor. Endothelin antagonism resulted in a dramatic reduction of lung metastases, similar to the effect of reexpressing RhoGDI2 in these metastatic cells. Taken together, these experiments show a novel approach of identifying therapeutic targets downstream of metastasis suppressor genes. The data also suggest that blockade of the ET-1 axis may prevent lung metastasis, a new therapeutic concept that warrants clinical evaluation.
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PMID:Endothelin axis is a target of the lung metastasis suppressor gene RhoGDI2. 1610 83

Bladder cancer is a major cause of new cancer diagnosis throughout the world. The standard therapy for muscle-invasive bladder cancer is radical cystectomy, while superficial bladder cancer can often be managed with serial resections or intravesical therapy. The 5-year overall survival for patients undergoing radical cystectomy is only about 50%, with the majority of deaths due to metastatic bladder cancer. For these patients and for those who have metastases at diagnosis, chemotherapy with the combination of methotrexate, vinblastine, doxorubicin, and cisplatin is still the standard treatment. Gemcitabine, taxanes, ifosfamide, and pemetrexed have also demonstrated activity in bladder cancer, allowing the development of less toxic chemotherapy regimens that are the subject of ongoing clinical research. Recent insights into the biology of bladder cancer, the introduction of new chemotherapy regimens, and randomized trials of perioperative chemo-therapy have significantly improved the outlook for patients with metastatic bladder cancer. Molecular markers appear to correlate with prognosis after cystectomy, but require further clinical validation and have not replaced pathologic staging for the purpose of making adjuvant treatment decisions. Recent advances in the fields of tumor genetics, angiogenesis, and tumor immunology have been applied in the ongoing development of novel treatment strategies for this challenging disease.
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PMID:Review of metastatic bladder cancer. 1676 Aug 84

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.
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PMID:Neoadjuvant chemotherapy for bladder cancer. 1711 30

Although bladder cancer is a chemosensitive tumor, metastatic disease is related with poor prognosis and short-term survival. For two decades, the treatment of choice for metastatic bladder cancer has been cisplatin-based chemotherapy. Nowadays, non-platinum regimes have been tested such as taxanes and gemcitabine, which is considered as an attractive alternative. In parallel, double and triplet combination chemotherapy have been assessed in clinical trials. Furthermore, individualized treatments through the identification of molecular prognostic factors and application of targeted therapy have gained considerable interest.
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PMID:Where are we with the treatment of metastatic bladder cancer? 1771 18

This article provides a review of bladder cancer etiology, diagnosis, and management for WOC nurses. Bladder cancer incidence continues to rise yearly in the United States, and patients with bladder cancer comprise some of the most challenging cases in urologic oncology. Nurses are involved with all aspects of the processes of care for the patient with bladder cancer, from initial diagnosis and treatment to postsurgical care and follow-up. For nonmuscle invasive bladder cancer, treatment includes transurethral resection followed by intravesical chemotherapy or immunotherapy to prevent recurrence or progression. Radical cystectomy along with chemotherapy protocols provides a survival advantage for muscle invasive bladder cancer, although the timing of chemotherapy remains controversial. Numerous factors are considered when determining the type of urinary diversion used at the time of radical cystectomy, but patient, family, surgeon, and nursing input are essential for preserving an optimal health-related quality of life and reducing morbidity. Patients with metastatic bladder cancer are generally treated with a cisplatin-based chemotherapy but continue to have a poor prognosis. Newer therapies involving novel molecular-targeted agents provide hope for the future for patients with metastatic disease.
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PMID:Current trends in the management of bladder cancer. 1960 62

The management of metastatic urothelial carcinoma (UC) of the bladder is a common and complex clinical challenge. Despite the fact that UC is one of the most frequent tumors in the population, long term survival for metastatic disease remains low, and chemotherapy is curative for only a small minority of patients. UC is genetically heterogeneous, and it is surrounded by a complex tissue microenvironment. The problems of clinical practice in the field of metastatic bladder cancer have begun to stimulate translational research. Advances in the understanding of the molecular biology of urothelial cancer continue to contribute to the identification of molecular pathways upon which new therapeutic approaches can be targeted. New agents and strategies have recently been developed which can direct the most appropriate choice of treatment for advanced disease. A review of literature published on the targeted therapy for metastatic bladder cancer is presented, focusing on the molecular pathways shut down by the new therapeutic agents.
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PMID:Targeted therapies in the management of metastatic bladder cancer. 1970 9

Muscle-invasive bladder cancer is an aggressive disease with at least 50% of patients dying from metastases within 2 years of diagnosis. The 5-year survival rate for metastatic bladder cancer is <15%. Although modern combination chemotherapy regimens have improved median survival from 6 to 14 months compared with best supportive care, there is still a great opportunity for improvement. New therapies and strategies for better patient and treatment selection are now being investigated for advanced bladder cancer. These include agents that target several pathways involved in the pathogenesis of the disease--such as growth factor receptors, angiogenic pathways, p53, cell cycle checkpoints and apoptosis--as well as novel chemotherapeutic agents. Results from recent and ongoing trials suggest that some of these agents could soon emerge as useful players to overcome the limitations of our present therapies.
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PMID:New agents for bladder cancer. 2094 43


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